Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Long-term follow-up data on young patients receiving amiodarone is lacking, especially in relation to growth and late side effects. The records of 95 young patients (mean age 12.4 years; range 3 weeks to 31.5 years) who received amiodarone were reviewed. Minimal follow-up time for those continuing to take amiodarone was 1.5 years; the mean duration of therapy was 2.3 years (maximal 6.5). The mean maintenance dosage was 7.7 (1.5 to 25) mg/kg body weight per day. Initial success (based on symptoms and 24 h electrocardiogram) was achieved in 23 of 34 patients with ventricular tachycardia, in 32 of 33 with atrial flutter and in 21 of 28 patients with supraventricular tachycardia. However, in 7 of 33 patients with atrial flutter, the arrhythmia returned after 6 months. Patient growth continued in the same percentiles achieved before amiodarone in all but eight patients, improving in six and worsening in two with severe underlying disease. Proarrhythmia occurred in three patients: one had torsade de pointes that disappeared when amiodarone administration was stopped; two with severe anatomic heart disease died suddenly during the loading period (one with atrial flutter and one with ventricular tachycardia). Side effects occurred in 28 (29%) of the 95 patients: keratopathy (in 11), abnormal thyroid function test (in 6), chemical hepatitis (in 3), rash (in 3), peripheral neuropathy (in 2), hypertension (in 1) and vomiting (in 1). All side effects disappeared when amiodarone was discontinued or the dose was reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term follow-up of amiodarone therapy in the young: continued efficacy, unimpaired growth, moderate side effects. 231 68

When used as first-line treatment for advanced ovarian cancer in phase III trials, single-agent carboplatin has produced clinical complete response rates comparable with or exceeding those of single-agent cisplatin. Phase I/II trials of combination chemotherapy have yielded overall objective response rates of 44% to 75% when carboplatin was combined with either cyclophosphamide or chlorambucil. In randomized phase III trials of carboplatin combination chemotherapy, response rates similar to those of cisplatin combinations have been achieved but with greatly reduced toxicities. The data from these phase I, II, and III trials show that carboplatin is as active as cisplatin in patients with advanced ovarian cancer and is associated with a significantly lower incidence and is associated with a significantly lower incidence of emesis, ototoxicity, peripheral neuropathy, and renal dysfunction. Thus, carboplatin should be considered the platinum compound of choice in the firstline treatment of advanced ovarian cancer.
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PMID:Carboplatin in the first-line chemotherapy of ovarian cancer. 240 22

A 27 year old male with metastatic testicular carcinoma was treated with cisplatin, vinblastine, and bleomycin (PVB) chemotherapy. After receiving a cumulative dose of 500 mg/m2 of cisplatin, he developed severe nausea and vomiting and had clinical evidence of a cisplatin-induced peripheral neuropathy. His vomiting resolved five weeks after discontinuation of cisplatin. We believe this case represents the first report of gastric autonomic neuropathy induced by cisplatin.
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PMID:Cisplatin-induced gastric paresis. 244 37

Twenty-three patients with nonresectable, recurrent cancer of the cervix were treated with a combination of cis-platinum and Mitomycin C. The overall response rate was 35% in 20 evaluable patients. Four patients (20%) achieved a complete response with a median duration of 9 months. Three patients (15%) achieved a partial response with a median duration of 11 months. The objective response rate was 33.4% for tumors within previously irradiated sites and 45% for distant metastases. The overall median survival was 10.3 months, and median progression-free interval was 6.7 months. Toxicity with this regimen was acceptable and consisted of nausea, vomiting, marrow suppression, and peripheral neuropathy. We conclude that this regimen is well tolerated with a low incidence of toxicity and can be safely administered on an out-patient basis. However, the superiority of this combination over cis-platinum alone remains to be determined.
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PMID:Treatment of recurrent cervical cancer with cis-platinum and mitomycin C: a phase II study. 250 64

Control of cisplatin-induced nephrotoxicity and nausea/vomiting has enabled the development of very high-dose cisplatin regimens (monthly total dose, 200 mg/m2). Neurotoxicity is now recognized to be the dose-limiting toxicity of these regimens. However, during a pilot study involving 5 mg/m2 vinblastine and 100 mg/m2 cisplatin given every 28 days on days 1 and 8 for the treatment of advanced non-small-cell lung cancer, we noted a high incidence of progressive peripheral neuropathy, which continued for several months after the discontinuation of cisplatin chemotherapy. Of the six patients treated, four received at least three cycles of therapy (median total cisplatin dose, 685 mg/m2; range, 500-725 mg/m2). All four patients developed a progressive peripheral neuropathy, with a worsening of toxicity by 1-3 grades over the 2-3 months after cisplatin discontinuation. One patient progressed from grade I (mild paresthesia) to grade IV (inability to ambulate) over a period of 3 months after the discontinuation of therapy. Stricter rules for early dose de-escalation and discontinuation may be required for very high-dose cisplatin regimens. Delayed progressive neuropathy should be recognized as a possible late complication of this form of therapy.
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PMID:Progressive paresthesias after cessation of therapy with very high-dose cisplatin. 255 19

Taxol, a novel antimicrotubule agent that enhances tubulin polymerization and microtubule stability, was administered to adults with refractory leukemias as a 24-h i.v. infusion in a Phase I study. The primary objectives were to determine the maximum tolerated dose of taxol administered on this schedule to patients with acute leukemias and describe the nonhematological toxicities which became dose limiting. The starting dose, 200 mg/m2, was based on the maximum tolerated dose in solid tumor trials, in which myelosuppression precluded dose escalation. Seventeen patients received 28 evaluable courses at 200, 250, 315, and 390 mg/m2. Severe mucositis limited further dose escalation. Other nonhematological effects included peripheral neuropathy, alopecia, myalgias, arthralgias, nausea, vomiting, diarrhea, and an acute pulmonary reaction that was presumptively due to taxol's Cremophor vehicle. Mean peak taxol plasma concentrations at all dose levels were in the range of concentrations that were previously demonstrated to induce microtubule bundles, a morphological effect associated with cytotoxicity, in leukemia cells in vitro. Pretreatment blasts from 12 patients were incubated with taxol ex vivo. Taxol-induced microtubule bundles were apparent in the blasts of eight patients who also had cytoreduction of tumor, and sensitivity to bundle formation was related to the magnitude of antitumor activity. In contrast, taxol did not induce microtubule bundles ex vivo in the blasts of the other four total nonresponders. Based on this study, the maximum tolerated doses and recommended Phase II doses for taxol, limited by nonhematological toxicity and administered as a 24-h i.v. infusion to patients with refractory leukemias, are 390 and 315 mg/m2. Phase II trials at these myelosuppressive doses are required to determine taxol's activity in the treatment of leukemias. In addition, further evaluation of microtubule bundle formation ex vivo in Phase II studies is necessary to determine the ultimate utility of this assay in assessing tumor sensitivity to taxol.
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PMID:Phase I and pharmacodynamic study of taxol in refractory acute leukemias. 256 75

Carboplatin, a new cisplatin analogue, appears as active as cisplatin in patients with advanced ovarian cancer, but in phase I and II trials has proven significantly less toxic. In single-agent phase II trials, carboplatin has been associated with clinical complete response (CR) rates of up to 13% and overall objective response rates of up to 32% in patients with prior cisplatin exposure. As first-line treatment in phase II trials, single-agent carboplatin has produced clinical CR rates ranging from 9% to 62% and overall objective response rates of 45% to 85%. In phase III trials in this patient population, single-agent carboplatin has been associated with clinical CR rates comparable with or exceeding those of single-agent cisplatin. Phase I/II trials of combination chemotherapy have yielded overall objective response rates of 44% to 75% when carboplatin was combined with either cyclophosphamide or chlorambucil. In randomized phase III trials of combination chemotherapy, response rates similar to those of cisplatin have been achieved. However, toxicities were greatly reduced in the carboplatin-treated patients. The data from these phase I, II, and III trials document that carboplatin is as active as cisplatin in patients with advanced ovarian cancer and is associated with a significantly lower incidence of emesis, ototoxicity, peripheral neuropathy, and renal dysfunction. Thus, carboplatin may become the platinum compound of choice in the first-line treatment of advanced ovarian cancer.
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PMID:Carboplatin in the treatment of ovarian cancer. 265 95

The elderly represent a special challenge to the physician in providing effective cancer chemotherapy. Though they represent the majority of the patients who eventually will need such therapy, until recently little information was available on its use in this population. There are variable age changes in pharmacokinetics, particularly in renal elimination of drug and metabolites, which may necessitate dosage amendment. Concomitant renal impairment or hepatic disease may further alter drug disposition. Other common pre-existing conditions in the elderly also may increase susceptibility to adverse drug effects. For example, the risk of toxicity from doxorubicin and vincristine can be increased in the presence of pre-existing cardiac disease or peripheral neuropathy, respectively. Because of the variability of the ageing process and the effects of concomitant disease, each patient must be assessed on an individual basis. Furthermore, in treatment planning, not only age and health status but also the patient's attitude and the tumour type are important considerations. Chemotherapy for most malignancies appears beneficial and well tolerated in the elderly, and there is little evidence that age per se is a determinant of chemotherapy regimen selection and dosing. The exceptions may be the curable haematological malignancies for which chemotherapy seems less efficacious and more toxic in geriatric than younger patients. The complications of chemotherapy such as vomiting, mucositis and bone marrow depression must be anticipated, diagnosed early and managed aggressively in aged patients. Guidelines are provided to help manage these problems. Chemotherapy in the elderly is still at a relatively early stage of development. Further research is required to establish optimal regimens for use in this population, in particular for curable haematological neoplasms.
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PMID:Problems in the use of anticancer drugs in the elderly. 266 Nov 98

The three best-described genetic polymorphisms of drug metabolism--the debrisoquin/sparteine type of oxidative polymorphism (hereafter referred to as the debrisoquin polymorphism), the polymorphism of N-acetylation, and the mephenytoin type of oxidative polymorphism--are reviewed. For all three polymorphisms, the poor-metabolizer phenotype is inherited as an autosomal recessive trait. The debrisoquin and mephenytoin oxidative polymorphisms involve defects in two separate cytochrome P450 enzymes. The prevalence of the poor-metabolizer phenotype for debrisoquin ranges between 2% and 10% for groups of various ethnic origins. The poor-metabolizer phenotype for mephenytoin comprises about 5% of the Caucasian population and about 20% of the Japanese population. N-acetyltransferase is a cytosolic enzyme whose clinical polymorphism was discovered using isoniazid as the substrate probe. The prevalence of the slow-acetylator phenotype among American and European Caucasian and American black groups is about 50%; among the Japanese it is about 10%. More than 20 agents are substrates for debrisoquin hydroxylase, about 15 for N-acetyltransferase, and 3-5 for mephenytoin. In poor metabolizers, debrisoquin can cause hypotension, and sparteine can cause blurred vision, headache, and dizziness. Clinical consequences of the slow-acetylator phenotype include increased susceptibility to systemic lupus erythematosus induced by procainamide and hydralazine, peripheral neuropathy induced by isoniazid, hydralazine, and dapsone, and sulfasalazine-induced dose-related leukopenia, nausea, vomiting, headache, and vertigo. After administration of mephenytoin, poor metabolizers have increased somnolence and intellectual impairment. Awareness of genetic polymorphisms of drug metabolism should improve understanding of interindividual variability in drug disposition and response.
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PMID:Polymorphic drug metabolism. 268 60

Lead poisoning resulting from exposure to lead in a domestic car battery workshop is reported in 10 children in 2 families. 2 girls, aged 2 10/12 and 1 8/12 years, respectively, from 1 of the families were hospitalized for investigation of nausea, vomiting, progressive muscular weakness and peripheral neuropathy. Serum lead levels were 52 and 49 mcg/dl, respectively. Subsequent screening of all members of this family, as well as those of the other family who lived in the same house, revealed abnormally elevated levels of serum lead in all the members of both families. The 2 girls were treated with chelating agents and improved clinically and their serum lead levels decreased to 29 and 34 mcg/dl, respectively. The domestic workshop was closed and the 2 families moved to another neighborhood. These cases illustrate the need to screen all family members and contacts of patients with lead poisoning, as well as the hazards of the uncontrolled use of lead in domestic workshops.
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PMID:[Lead poisoning in two families from a car battery workshop]. 270 78


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