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)

PHIC [NSC-350602; (1,2-diaminocyclohexane) (isocitrato) platinum (II)] is a new highly water-soluble platinum derivative. Preclinical studies showed antitumor activity on a wide range of tumors, no cross-resistance with cisplatin and little or no nephrotoxicity in mice and baboons. A phase I clinical trial was then initiated at doses of 300 mg/m2 infused intravenously over one hour without induced diuresis or hydration. Dosages were escalated up to 1500 mg/m2. A total of 29 patients received 52 courses of treatment. The most important side-effect is thrombocytopenia which is rapidly reversible. Nausea and/or vomiting were mild or moderate with onset 1 hr after the end of the infusion and seldom persisted beyond 24 hrs. Measurements of biological parameters did not reveal significant evidence of nephrotoxicity except in one patient who developed urinary tract infection and for whom hemodialysis became necessary. No change in the audiogram could be demonstrated. Peripheral neuropathy was documented in one patient, and in two other patients to whom morphine was given confusional episodes were observed. Although no antitumor effect was observed, there was apparent stabilization of disease. Pharmacokinetic parameters were calculated in twelve out of these 29 patients. Based upon total platinum plasma concentrations, the elimination half-life is 58.3 hrs and the plasma clearance is 21.2 ml/min with an apparent volume of distribution of 7.6 liters. However, considering both plasma concentrations and urinary excretion, we could estimate the half-life of free filterable species (60 min), the plasma clearance (125 ml/min) and the renal clearance (86 ml/min). Mean urinary excretion is 64.4% of the dose after 6 days and 53.1% at 24 hrs. Other administration protocols are suggested, based upon these pharmacokinetic parameters.
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PMID:Preliminary phase I clinical study and pharmacokinetics of (1,2-diaminocyclohexane) (isocitrato) platinum (II) or PHIC. 380 Mar 20

Seventeen patients with advanced non-small-cell lung cancer (NSCLC) were entered on a combination chemotherapy protocol including vindesine and high-dose cisplatin. All patients had measurable disease and had not previously received chemotherapy. All patients entered were evaluable for toxicity and response. Tumor regression was limited to one complete and one partial response (response rate, 11.7%; 95% confidence limits, 0 to 27%). The complete and partial response lasted 260 + and 82 days, respectively. For the 15 nonresponding patients, the median time to disease progression was 76 days. Median survival was 141 days for the whole group. Significant toxic effects were vindesine-related peripheral neuropathy and cisplatin-induced emesis. Myelosuppression was mild and manageable. The response for the vindesine-cisplatin combination observed in our study is inferior to that seen in a previous vindesine-cisplatin trial reported by others. Thus, the true value of this two-drug regimen in the treatment of NSCLC remains to be established.
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PMID:Vindesine and high-dose cisplatin in the treatment of advanced non-small-cell lung cancer. 403 26

A neuropsychiatric syndrome developed in four patients 2 1/2-9 months after gastric partition for morbid obesity. Since the partition, all four patients had recurrent severe vomiting with severe weight loss (52 to 100 lb) and they had not had vitamin supplementation. Two patients had peripheral neuropathy along with confusion and memory loss of recent events. The other two had peripheral neuropathy alone. Vitamin B complex replacement was especially helpful in the management of these patients. Peripheral neuropathy completely resolved in one of the patients, whereas the other three patients were left with residual weakness in their extremities and two had recent memory loss. Awareness of this complication may result in early recognition and treatment in the postgastric partition patient.
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PMID:Neuropsychiatric syndromes after gastric partition. 630 87

Thirty-eight women with advanced ovarian cancer were given monthly cycles of intravenous cyclophosphamide, Adriamycin (doxorubicin) and cis-platin, and oral hexamethylmelamine. Of 26 with tumor which would be evaluated for response, 42% had complete remission and 50% partial remission. Median time to disease progression from entry for all 38 patients was 13 months, and median survival 23.5 months. The bulk of tumor at the time chemotherapy was begun was the only significant prognostic factor for time to disease progression and survival. Of the seven women surviving free of disease a median of three years later, five had no mass greater than 2 centimeters in diameter at entry. Toxicity was predominantly myelosuppression and vomiting, with mild peripheral neuropathy in 27% and no significant renal or cardiac toxicity. The response rate of 92% is much higher than that previously reported with melphalan, and the survival considerably longer. The toxicity is acceptable, given the substantial improvement in results.
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PMID:Cis-platin based combination chemotherapy for advanced ovarian cancer. High overall response rate with curative potential only in women with small tumor burdens. 640 47

A recently introduced rodenticide containing N-3-pyridylmethyl N'-p-nitrophenyl urea (PNU), Vacor, was accidently ingested by a 25-month-old child, resulting in acute vomiting, lethargy, seizures, and hypoglycemia, as well as chronic evidence of autonomic and peripheral neuropathy and glucose intolerance. Treatment with niacinamide (nicotinamide), may have been of benefit since all problems were resolved within three months of ingestion. This agent (PNU) is remarkably similar chemically and toxicologically to alloxan and streptozocin, both potent beta-cell toxins. These similarities are not only important in regard to the antodite for PNU, but they also suggest that the toxin m,y cause long-term endocrinologic, neurlogic, and oncologic problems.
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PMID:Accidental ingestion of Vacor rodenticide: the symptoms and sequelae in a 25-month-old child. 644 44

Abnormalities in the function of the stomach in patients with long-standing diabetes mellitus, usually insulin-dependent, may provide difficult management problems. There is a reduced frequency of peptic ulcer disease in diabetics. Gastric atrophy, often with parietal cell antibodies, is common and the frequency of pernicious anemia with its expected intrinsic factor antibodies is increased. Gastric analysis results have been conflicting but generally suggest that long-standing diabetics have lower acid levels than normals, possibly secondary to vagal neuropathy. Gastric atony occurring in a small but significant number of patients with longstanding insulin-dependent diabetes, usually with a clinically apparent peripheral neuropathy, has been associated with upper abdominal discomfort, vomiting, and a clinical picture of gastric outlet obstruction. Various degrees of subclinical delays in gastric emptying are probably present in many asymptomatic patients and, indeed, are underemphasized contributors to poor control of blood sugar levels. Studies utilizing radioactive-labeled physiological meals have demonstrated abnormalities in the gastric emptying of solids, in particular, and sometimes liquids in the latter stages of the disease. Metoclopramide, a dopamine antagonist, which stimulates upper gastrointestinal smooth musculature, results in accelerated gastric emptying; clinical trials have shown that it is capable of alleviating symptoms related to diabetic gastroparesis and with its recent approval and release in this country, it promises improved management of this entity. Another agent, domperidone, a selective peripheral dopamine antagonist with no appreciable side effects, is in this country an investigational drug which has shown clinical efficacy in Europe in improving gastric stasis syndromes.
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PMID:Diabetes and the stomach. 665 60

Two weeks after gastric partitioning for morbid obesity, a 45-year-old woman experienced persistent vomiting that led to a weight loss of 30 kg over 6 weeks. Wernicke's encephalopathy and peripheral neuropathy developed. The Wernicke's encephalopathy responded well to the administration of thiamine. This is one of very few reported cases of Wernicke's encephalopathy following gastric partitioning.
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PMID:Wernicke's encephalopathy after gastric partitioning for morbid obesity. 670 23

Forty-nine women received a combination of cis-platinum and hexamethylmelamine (36 also received doxorubicin) for advanced ovarian cancer progressing after therapy that included an alkylating agent or extended field radiation. Twenty-six (53%) had an objective remission that lasted a median of 6 months from start of treatment. Response rate was independent of age, extent of prior therapy, and performance status. A long interval from initial diagnosis to entry, response to therapy, and ambulatory performance predicted improved survival from entry. No patient is surviving free of disease. Myelosuppression and vomiting were moderately severe but tolerable. Azotemia and peripheral neuropathy were infrequent and milk. These drugs have major activity in this poor-risk group and should be studied as part of initial therapy when enhanced efficacy and reduced toxicity are to be expected.
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PMID:Combination chemotherapy of advanced ovarian cancer with hexamethylmelamine, cis-Platinum, and doxorubicin after failure of prior therapy. 677 57

A short review is given of the pharmacokinetic characteristics and side effects of the nitroimidazoles: metronidazole, tinidazole and ornidazole. The drugs are well absorbed from the gastrointestinal tract, maximum plasma levels generally being obtained 1 to 4 h after oral intake. Metronidazole has been shown to be absorbed after rectal administration; vaginal absorption is documented for all three drugs. The nitroimidazoles are widely distributed in the body, cross the placenta and appear in breast milk. Therapeutically effective concentrations of e.g. metronidazole have been demonstrated in e.g. the central nervous system, middle ear discharges, bile, peritoneal fluid, and fluids and tissues of the female genital tract. The binding to plasma proteins is less than 20%. Available data suggest that the elimination half-lives of these drugs differ, being 7-8 h for metronidazole, about 12 h for tinidazole and 14-15 h for ornidazole. Both metronidazole and ornidazole, but not tinidazole, seem to be extensively metabolized before elimination. The nature and frequency of adverse reactions to this drug include encephalopathy in a few patients treated with doses between 5 and 10 g daily as an adjunct to radiotherapy, and peripheral neuropathy observed in patients treated for prolonged periods with high doses. Among the common side effects of the nitroimidazoles are symptoms from the gastrointestinal tract such as nausea, anorexia, vomiting and metallic or bitter taste. Dizziness, ataxia and headache have been reported. When given together with alcohol, a disulfiram-like intolerance reaction can be obtained.
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PMID:Pharmacokinetics of nitroimidazoles. Spectrum of adverse reactions. 694 57

Twenty-six women with advanced or recurrent endometrial cancer were treated with cisplatin at a dose of 50, 70, or 100 mg/m2 every 4 weeks. An objective response was obtained in 11 of 26 patients (42%), with 10 partial responses and 1 complete response. The median duration of remission was 5 months, with a range of 2 to 11 months. The complete response lasted 8 months. Five patients had stable disease lasting an average of 5 months. One of 6 patients (16.6%) responded to cisplatin at a dose of 50 mg/m2, 4 of 7 (57%) responded to the dose of 70 mg/m2, and 6 of 13 (46%) responded to the dose of 100 mg/m2, but the differences were not statistically significant (P = .2). In 8 of 26 cases (31%) cisplatin was discontinued because of toxicity. Three patients developed a peripheral neuropathy, 1 patient refused further therapy because of vomiting, 2 patients had nephrotoxicity, and 2 others had both nephrotoxicity and neurotoxicity. The average total cumulative dose of cisplatin administered when renal deterioration and neuropathy occurred was approximately 500 mg/m2. Cisplatin is definitely active against endometrial cancer, but toxicity precludes its prolonged administration in high doses on an outpatient basis. By maintaining a forced diuresis, toxicity can probably be decreased, thereby permitting continued administration of cisplatin. The drug may also be more useful when used at a lower dose in combination with other active agents against endometrial cancer.
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PMID:Cisplatin chemotherapy for disseminated endometrial cancer. 704 39


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