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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a double-blind randomized trial, imipenem/cilastatin (I/C; 500 mg every 6 hours) and ampicillin/sulbactam (A/S; 3 g every 6 hours) were compared in regard to their efficacy for initial empirical and definitive parenteral treatment of limb-threatening pedal infection in diabetic patients. The major endpoints of treatment were cure (resolution of soft-tissue infection), failure (inadequate improvement, necessitating a change in antibiotic therapy), and eradication (clearance of all pathogens from the wound and any bone cultures). Patients in the two treatment groups were similar in regard to the severity of diabetes; presence of neuropathy and peripheral vascular disease; site and severity of infection; pathogen isolated; and frequency of osteomyelitis (associated with 68% of the 48 A/S-treated infections and 56% of the 48 I/C-treated infections). After 5 days of empirical treatment, improvement was noted in 94% of the A/S and 98% of the I/C recipients. At the end of definitive treatment (days' duration [mean +/- SD]: 13 +/- 6.5 [A/S], 14.8 +/- 8.6 [I/C]), outcomes were similar: cure, 81% (A/S) vs. 85% (I/C); failure, 17% (A/S) vs. 13% (I/C); and eradication, 67% (A/S) vs. 75% (I/C). Treatment failures were associated with the presence of antibiotic-resistant pathogens and possible nosocomial acquisition of infections. The number of adverse events among patients in the two treatment groups was similar: 7 in the A/S group (4 had diarrhea and 3 had rash) and 9 in the I/C group (5 had diarrhea, 2 had severe nausea, 1 had rash, and 1 had seizure). Efficacy of A/S and I/C is similar for initial empirical and definitive treatment of limb-threatening pedal infection in patients with diabetes.
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PMID:Use of ampicillin/sulbactam versus imipenem/cilastatin in the treatment of limb-threatening foot infections in diabetic patients. 807 57

We studied the clinical, biochemical, and genetic features of eight patients with the autosomal recessive mitochondrial syndrome mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). MNGIE is clinically characterized by ophthalmoparesis, peripheral neuropathy, leukoencephalopathy, gastrointestinal symptoms (recurrent nausea, vomiting, or diarrhea) with intestinal dysmotility, and histologically abnormal mitochondria in muscle. Brain MRI scans were consistent with leukodystrophy in seven patients examined. Nerve conduction and EMG studies were compatible with a sensorimotor neuropathy; quantitative EMG of two patients suggested a myogenic process. Muscle mitochondrial enzyme analysis revealed a partial defect of cytochrome c oxidase activity in five patients; three had additional respiratory chain enzyme defects. Two patients had isolated complex I defects, and one had normal respiratory chain function. Southern blot analysis revealed multiple deletions of mitochondrial DNA in four of eight patients.
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PMID:Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): clinical, biochemical, and genetic features of an autosomal recessive mitochondrial disorder. 816 33

Cisplatin combined with cyclophosphamide has been considered a very active treatment for advanced ovarian cancer. Unfortunately, cisplatin is associated with dose-limiting neurotoxicity, as well as possible neuropathy, ototoxicity, and occasional renal dysfunction. Carboplatin, a cisplatin analogue, is active against advanced ovarian cancer, with a presumed lower incidence of emesis, ototoxicity, neuropathy, and renal dysfunction. The Southwest Oncology Group initiated a phase III randomized trial, in which 342 patients with stage III (suboptimal disease) and stage IV ovarian cancer were randomly assigned to treatment with six courses of intravenous cisplatin 100 mg/m2 plus cyclophosphamide 600 mg/m2 or carboplatin 300 mg/m2 plus cyclophosphamide 600 mg/m2. The median survival for the cisplatin arm was 17.4 months; for the carboplatin arm, median survival was 20.0 months. The null hypothesis of a 30% survival superiority with the cisplatin arm was rejected at the p = 0.02 level. Clinical response rates were 52% for the cisplatin arm and 61% for the carboplatin arm. There was less thrombocytopenia in the cisplatin arm (p < 0.001); however, there was less nausea and emesis (p < 0.001 for courses one to five), renal toxicity (p < 0.001), anemia (p < 0.001), hearing loss (p < 0.001), and neuromuscular toxicity (p < 0.001) in the carboplatin arm. Carboplatin/cyclophosphamide proved to have a significantly better therapeutic index than cisplatin/cyclophosphamide in these patients with advanced ovarian cancer.
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PMID:Results of a Southwest Oncology Group phase III trial of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide in advanced ovarian cancer. 823 97

Ormaplatin is a cisplatin analog which has demonstrated activity against cisplatin-resistant tumors in preclinical studies. We delivered 28 cycles to 14 patients in a phase I trial of intraperitoneal ormaplatin given every 28 days. The maximum tolerated dose was 88.4 mg/m2 and acute dose-limiting toxicity was abdominal pain. Other toxicities include nausea, emisis, fever, and severe neuropathy seen in 1 patient at a cumulative dose of 399 mg/m2. No objective responses were observed. Hematologic toxicity was mild. The dose recommended for future trials of intraperitoneal ormaplatin is 66.5 mg/m2. Pharmacokinetic analysis performed at a dose of 66.5 mg/m2 demonstrated that the initial phase of elimination from the peritoneal cavity follows first-order kinetics with k = 0.69 hr-1 and half-life of 1.4 hr. Plasma pharmacokinetic behavior is best described by biexponential model with k1 = 0.369 hr-1, k2 = 0.107 hr-1, and first half-life of 2.9 hr and second half-life of 8.4 hr. Pharmacologic advantage, calculated by ratio of peritoneal to plasma AUC, is 17.1. If site-specific activity is demonstrated, then the intraperitoneal route of administration of ormaplatin at 66.5 mg/m2 may be beneficial.
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PMID:Phase I and pharmacokinetic study of intraperitoneal ormaplatin. 824 79

The aim of this study was to evaluate gallbladder dynamics in insulin-dependent diabetic patients with and without autonomic neuropathy. Gallbladder dynamics was studied by a scintigraphic method after a test meal in 26 insulin-dependent diabetic patients and 10 normal individuals. The presence and severity of autonomic neuropathy were defined according to the number of abnormal cardiovascular reflex tests: absent (no abnormal test), mild (1-3 abnormal tests), and severe (4-5 abnormal tests). The time from the moment when the patient started to take the test meal to the beginning of gallbladder emptying was longer (P = 0.01) in diabetic patients with mild (N = 11, 12.1 +/- 7.6 min) and severe neuropathy (N = 8, 11.0 +/- 10.6 min) than diabetic patients without autonomic neuropathy (N = 7, 3.9 +/- 4.4 min) and controls (N = 10, 4.8 +/- 4.2 min). The ejection rate was higher (P = 0.02) in the group with severe autonomic neuropathy (N = 8, 5.1 +/- 3.3%/min) than diabetic patients with mild (N = 11, 2.0 +/- 1.0%/min) or without autonomic neuropathy (N = 7, 1.8 +/- 0.8%/min) and controls (N = 10, 2.6 +/- 1%/min). Thirty-two percent of the diabetic patients with autonomic neuropathy presented increased perspiration, nausea and urgency to defecate after the ingestion of the test meal. A significant positive correlation of ejection rate with the presence of these symptoms (biserial point correlation test = 0.67, P < 0.01) was also observed. These data suggest that insulin-dependent diabetic patients with autonomic neuropathy present abnormalities of gallbladder emptying that could be related to specific gastrointestinal symptoms.
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PMID:Abnormalities in gallbladder dynamics of type 1 (insulin-dependent) diabetic patients with autonomic neuropathy. 855 72

Carboxyamido-triazole (CAI) is a synthetic inhibitor of non-excitable calcium channels that reversibly inhibits angiogenesis, tumor cell proliferation, and metastatic potential. Inhibition of calcium influx and calcium-dependent events is a potential common mechanism underlying these effects of CAI. The cytostatic and antiangiogenic properties of CAI led to its development for clinical investigation. In a Phase I clinical trial open to patients with refractory solid tumors, 49 patients received p.o. administered CAI daily or every other day. Two oral formulations, PEG-400 CAI solution and a gelatin capsule containing CAI in PEG-400, were tested. All administered dosages of CAI yielded plasma concentration at or above the range demonstrated to be effective in inhibiting signaling and cancer progression in vitro and in preclinical models (1 microgram/ml, 2.3 microM). Toxicity of p.o. administered CAI most commonly consisted of dose-related grade 1-2 nausea, vomiting, and occasional anorexia. CAI administration at bedtime ameliorated gastrointestinal complaints in many patients; others required addition of simple antiemetic regimens, usually consisting of metoclopropamide or prochlorperazine. Gastrointestinal complaints were the cause for compliance-limiting toxicity at 175 mg/m2/day of the liquid formulation and 125 mg/m2/day of the gelatin capsule formation. Reversible and rare sensory axonal neuropathy (grade 3, 1 patient) and neutropenia (grade 4, 1 patient) were dose-limiting toxicities observed at the 330 mg/m2 every-other-day liquid CAI dose level. No evidence of cumulative end organ damage or central nervous system injury was observed. Disease stabilization and improvement in performance status was observed. Disease stabilization and improvement in performance status was observed in 49% of evaluable patients who had disease progression before CAI. Disease stabilization and associated improvement in performance status was seen in patients with renal cell carcinoma (7 months), pancreaticobiliary carcinomas (3, 5, and 5 months), melanoma (7 months), ovarian cancer (7 months), and non-small cell lung cancer (3 months). The recommended Phase II doses from this trial are 150 mg/m2/day in the liquid formation and 100 mg/m2/day in the gelatin capsule formation.
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PMID:Clinical investigation of a cytostatic calcium influx inhibitor in patients with refractory cancers. 856 73

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is active against advanced breast cancer and anthracycline-resistant breast cancer. We assessed the efficacy and toxicity of doxorubicin followed by a 3-hour infusion of paclitaxel in women with advanced breast cancer. Participants could have received at most one prior adjuvant chemotherapy regimen, but no previous exposure to anthracyclines or taxanes was permitted. The patients were treated every 3 weeks with doxorubicin (50 or 60 mg/m2) followed 30 minutes later by paclitaxel (155, 175, or 200 mg/m2). After reaching the maximum cumulative doxorubicin dose, treatment could be continued with paclitaxel alone. Thirty women were included, of whom 29 were evaluable for response. The overall response rate was 83% (95% confidence interval, 64% to 94%), with 24% of patients attaining complete remission. Median response duration for complete responders was 8+ months (range, 4 to 13 months) and median time to progression was 9 months (range, 2 to 18 months). Main toxicities were neutropenia, paresthesia, nausea/vomiting, alopecia, myalgia, and cardiotoxicity. In 15 patients (50%), the left ventricular ejection fraction decreased to below normal levels; six patients (20%) developed congestive heart failure. In conclusion, the combination of doxorubicin and paclitaxel is highly active; dose-limiting toxicities are neutropenia, neuropathy, and cumulative cardiotoxicity.
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PMID:Doxorubicin and paclitaxel, a highly active combination in the treatment of metastatic breast cancer. 889 95

In studies conducted by the Eastern Cooperative Oncology Group, treatment with either paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) or carboplatin was associated with an improvement in 1-year survival in patients with stage IV non-small cell lung cancer (NSCLC). Based on these findings, a phase II trial of carboplatin plus paclitaxel was conducted in patients with advanced NSCLC to determine the activity and toxicity of this regimen. Eligibility requirements included stage IIIB or IV histologically confirmed NSCLC, Eastern Cooperative Oncology Group performance status of 0 to 2, no prior chemotherapy, and adequate hematologic, renal, hepatic, and cardiac functions. Paclitaxel was administered intravenously over 24 hours at a dose of 135 mg/m2 (28 patients) or 175 mg/m2 (23 patients), followed by a 1-hour infusion of carboplatin on day 2. Carboplatin was administered at a dose of 300 mg/m2 (16 patients) or, using the Calvert formula, a dose calculated to achieve an area under the concentration-time curve of 6 mg/mL x min (35 patients). Treatment was repeated every 28 days for a total of six cycles. Among the 51 eligible patients, 34 were men and 17 were women; their median age was 60 years and their median Eastern Cooperative Oncology Group performance status was 1. Six patients had stage IIIB and 45 had stage IV disease. Grade 3 or 4 granulocytopenia and thrombocytopenia were observed in 47% and 3% of treatment cycles, respectively. The most common nonhematologic toxicities noted included nausea and emesis, neuropathy, and arthralgia and myalgia. There were no complete responses and 14 partial responses, for an overall response rate of 27% (95% confidence interval, 17% to 41%). Median survival was 38 weeks and the survival rate at 1 year was 32%. Paclitaxel plus carboplatin, as given in this study, was found to be a moderately active regimen in patients with advanced NSCLC. This regimen warrants comparison with existing cisplatin-based regimens in a prospective randomized trial.
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PMID:Paclitaxel plus carboplatin in the treatment of patients with advanced lung cancer: a Vanderbilt University Cancer Center phase II trial (LUN-46). 900 20

Fialuridine is an antiviral agent with potent activity against hepatitis B virus replication in vitro and in vivo. In a phase II study, 7 of 15 patients experienced severe toxicity due to the drug after 9 to 13 weeks of treatment. Adverse effects included nausea, vomiting and painful paraesthesia; subsequently, hepatic failure, pancreatitis, neuropathy, myopathy and lactic acidosis developed, probably due to multisystem mitochondrial toxicity. Possible mechanisms of fialuridine toxicity include mitochondrial injury and pyruvate oxidation inhibition. While other nucleoside analogues have shown evidence of inducing mitochondrial injury (zidovudine, didanosine, zalcitabine), others to date have not (lamivudine, famciclovir). Specific recommendations for future study of existing and new nucleoside analogues include testing for toxicity after prolonged incubation, specific investigations to measure mitochondrial function, toxicological tests and well designed clinical trials with appropriate testing to monitor for any adverse effects on mitochondrial integrity and function.
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PMID:Mitochondrial injury. Lessons from the fialuridine trial. 925 27

Nausea, vomiting, and abdominal pain are common symptoms that suggest many diagnoses. The patient's symptoms may be related to an anatomical defect such as a peptic ulcer or a mechanical small bowel obstruction. However, no anatomical abnormality may be identified despite radiological, endoscopic, or laboratory studies. The cause of the patient's symptoms may have significant impact on the patient's quality of life (nonulcer dyspepsia) and life span (intestinal pseudo-obstruction). Abnormal antroduodenal motility may be the underlying cause of the patient's symptoms. Normally, coordinated phasic contractions in the stomach and small intestine maintain digestion and absorption of food. A prolonged set of phasic contractions (phase 3 of the migrating complex) begins in the stomach and propagates down the small intestine to excrete nondigestible foods, bacteria, and dead cells. Any disturbance in the normal motility pattern can lead to maldigestion and symptoms of upper intestinal dysfunction. Objective tests of motility disturbances in the stomach and small intestine include measurement of gastric emptying, intestinal transit, contractions of the stomach and duodenum, and electrogastrography. Abnormal antroduodenal motility may be secondary to an abnormality in the smooth muscle (myopathy) or the nerves in controlling smooth muscle contractions (neuropathy). Antroduodenal motility measurements may help identify a partial small bowel obstruction, the cause of small intestinal overgrowth, and the cause of chronic abdominal visceral pain. Motility studies may suggest useful drugs for correcting the underlying pathophysiology and relieving symptoms.
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PMID:Role of motility measurements in managing upper gastrointestinal dysfunction. 953 Nov 16


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