Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platelet serotonin, dopamine and norepinephrine concentrations were determined with sensitive and specific radioenzymatic methods in normal volunteers and in sick subjects with both normal and increased serotonin production. In the assays, a 3H-labeled methyl group is transferred from [3H]S-adenosyl methionine to the monoamine under investigation by a semi-purified enzyme. The platelet serotonin concentration (expressed as pmol serotonin/mg platelet protein) was significantly higher in the patients with increased serotonin production from carcinoid tumors (5400 +/-0 500) than in the normal volunteers (900 +/- 100) or the sick subjects with normal serotonin production (900 +/- 100). Although eight of the subjects with increased serotonin production had symptoms of the carcinoid syndrome such as flushing and diarrhea, two of the subjects with increased serotonin production did not have these symptoms. The radioenzymatic method of platelet serotonin measurement was as effective as a conventional fluorometric technique for serum serotonin in detecting patients with serotonin overproduction from carcinoid tumors, and had the advantages of being more sensitive and specific. The great sensitivity and specificity of the radioenzymatic techniques suggest that it might be useful in evaluating disease states in which platelet serotonin is decreased. Using these techniques we found that dopamine and norepinephrine were also present in platelets, although in much lower amounts than serotonin. Despite the markedly increased serotonin concentration in the platelets of subjects with serotonin overproduction from carcinoid tumors, there was no alteration in the dopamine or norepinephrine concentration of their platelets.
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PMID:Radioenzymatic assay of platelet serotonin, dopamine and norepinephrine in subjects with normal and increased serotonin production. 616 11

We describe a patient treated with trazodone, isocarboxazid, and methylphenidate hydrochloride who developed confusion, agitation, poor concentration, rigidity, myoclonus, involuntary movements, orthostatic hypotension, and hyperreflexia. CK was normal, and the syndrome resolved spontaneously over 12 hours. The serotonin syndrome occurs following the use of serotomimetic agents (serotonin reuptake inhibitors, tricyclic and tetracyclic antidepressants, tryptophan, 3,4-methylenedioxy-methamphetamine, dextromethorphan, meperidine, S-adenosylmethionine) alone or in combination with monoamine oxidase inhibitors. It is characterized by various combinations of myoclonus, rigidity, hyperreflexia, shivering, confusion, agitation, restlessness, coma, autonomic instability, low-grade fever, nausea, diarrhea, diaphoresis, flushing, and rarely, rhabdomyolysis and death.
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PMID:Serotonin syndrome. 785 15

A single-agent dose-escalating Phase I and pharmacological study of the polyamine synthesis inhibitor SAM 486A was performed. A dosing regimen of four weekly infusions followed by 2 weeks off therapy was studied. Fifty patients were entered into the study. Dose levels studied were 1.25, 2.5, 5, 8, 16, 32, 48, 70, 110, 170, 270, and 325 mg/m2/week. Pharmacokinetic sampling was done on day 1, and trough samples were taken weekly during the first treatment cycle. Pharmacodynamic sampling was done on days 1 and 22. At 325 mg/m2/week, dose-limiting toxicity was seen (one patient each with grade 4 febrile neutropenia, grade 3 neurotoxicity, and grade 3 hypotension with syncope and T-wave inversions on electrocardiogram). The recommended dose for further testing was set at 270 mg/m2/week. Infusion time was increased from 10 to 180 min due to facial paresthesias and flushing and somnolence. Drug exposure increased linearly with dose. Mean +/- SD t1,2 at 70-325 mg/m2 doses was 61.4+/-26.2 h, with a large volume of distribution at steady state. In peripheral blood leukocytes, a clear relationship between dose and inhibitory effect on S-adenosylmethionine decarboxylase or changes in intracellular polyamine pools was not recorded. SAM 486A can be administered safely using a dosing regimen of four weekly infusions followed by 2 weeks off therapy. The recommended dose for Phase II studies using this regimen is 270 mg/m2/week.
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PMID:Phase I and pharmacological study of weekly administration of the polyamine synthesis inhibitor SAM 486A (CGP 48 664) in patients with solid tumors. European Organization for Research and Treatment of Cancer Early Clinical Studies Group. 1081 92