Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Imipenem/cilastatin is the first of a new class of beta-lactam antibiotics called carbapenems. The antibacterial spectrum of imipenem exceeds any antibiotic investigated to date and includes gram-positive, gram-negative, and anaerobic organisms. Only methicillin-resistant organisms, Strep. faecium, Pseudomonas cepacia, and Pseudomonas maltophilia have been shown to be resistant. Imipenem is administered in a 1:1 ratio with cilastatin, which inhibits a renal enzyme (dehydropeptidase) and improves urinary recovery of imipenem. The elimination half-life of both compounds is 1.0 hours and recommended doses are 0.25-0.5 g iv q6h. Adverse events are similar in nature and incidence to beta-lactam antibiotics, with phlebitis/thrombophlebitis, diarrhea, nausea, skin rash, and elevations of hepatic enzymes most common. Clinical studies in phase II and III trials have shown imipenem/cilastatin to be effective in soft tissue infections, endocarditis, obstetrics and gynecology, complicated urinary tract infections, mixed anaerobic-aerobic infections, osteomyelitis, bacteremias, and pneumonias. Several comparative clinical trials have shown imipenem/cilastatin to be equal in efficacy to combination therapy. Imipenem/cilastatin may prove to be an alternative to combination antibiotic therapy because of its extremely broad spectrum of activity.
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PMID:Imipenem/cilastatin: the first carbapenem antibiotic. 391 Mar 85

KW-2083 [7-n-(p-hydroxyphenyl)-mitomycin C] is a new mitomycin C (MMC) derivative. Its myelotoxicity was compared with that of MMC by using colony-forming unit-spleen (CFU-S) from the femurs of C57BL/6 mice. As a result, it was estimated that the intensity of myelotoxicity of MMC was four times greater than that of KW-2083. Based on this data, a clinical trial of KW-2083 was conducted in 24 cases with various types of advanced solid tumors. KW-2083 was administered by i.v. injection at a dose of 40 mg/body every week. Out of 15 evaluable cases, a case of ovarian cancer showed a partial response. One case of each of ovarian cancer and gastric cancer showed minor response. However, as with mitomycin C, the dose-limiting toxicity of KW-2083 was leukopenia and thrombocytopenia. Other toxicities encountered were nausea, vomiting, anorexia, phlebitis and hepatic dysfunction. There were no cases with renal toxicity. Plasma concentration of KW-2083 was bioassayed in 3 cases who received 40 mg/body as an i.v. bolus injection. Plasma concentration-time curves fitted to a one-compartment model and half-life values averaged 27.6 min. The effective and low toxic dose schedules of KW-2083 should be investigated further.
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PMID:[A clinical trial of a new mitomycin C derivative, KW-2083 (7-N-(p-hydroxyphenyl)-mitomycin C)]. 403 9

9,10-Anthracenedicarboxaldehyde bis[(4,5-dihydro-1 H-imidazol-2-yl)hydrazone] dihydrochloride (CL216,942) is a new anthracene bishydrazone derivative that was evaluated in a Phase I clinical trial. The schedule of administration consisted of a single i.v. injection repeated at 4-week intervals. Twenty-eight patients received a total of 61 courses of the drug in a dose range of 20 to 280 mg/sq m. Leukopenia was the dose-limiting toxicity. It was of short duration and reversible. A drug-induced hypotension was noted at higher doses in three patients. The hypotension was not dose limiting, it was reversible, and it could largely be avoided by prolonging the drug infusion time to 1 hr. One patient with unsuspected severe coronary artery disease died of complications of myocardial infarction subsequent to a hypotensive episode. Significant phlebitis was also noted at higher doses of drug. This degree of phlebitis could be lessened by diluting the drug in larger volumes of fluid. Three patients experienced diaphoresis, nausea, palpitations, and chest discomfort at the conclusion of the infusions. None of the patients had electrocardiographic changes. Mild fever, alopecia, and nausea and vomiting were noted occasionally. One patient with a hypernephroma and one patient with hepatocellular carcinoma experienced partial responses of their tumors secondary to the drug. Phase II studies of CL216,942 are planned at a starting dose of 260 mg/sq m as a single dose repeated at 21- to 28-day intervals.
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PMID:Phase I clinical investigation of 9,10-anthracenedicarboxaldehyde bis[(4,5-dihydro-1 H-imidazol-2-yl)hydrazone] dihydrochloride (CL216,942). 626 75

Intravenous miconazole can produce responses in patients with various manifestations of coccidioidal disease, even if they have failed to respond to amphotericin B. In 4 large series of 33, 33, 46 and 31 courses of miconazole for skin and soft tissue, chronic pulmonary, meningeal and skeletal coccidioidomycosis, response rates of 40, 72, 31 and 32%, respectively, were achieved; 60, 75, 78 and 56%, respectively, of those responding subsequently relapsed at the site(s) of earlier involvement. This suggests that the therapeutic effect of the relatively brief courses used (mean, 1 to 3 months) is fungistatic in vivo. Common side effects of intravenous miconazole include phlebitis, pruritus, anaemia, thrombocytosis, hyponatraemia, nausea, hyperlipidaemia, vomiting, central nervous system effects, and rashes. The place of miconazole relative to amphotericin B and ketoconazole has not been determined, and requires further comparative studies. Information on the results of different regimens, particularly longer courses, would also be of interest.
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PMID:Miconazole in the treatment of coccidioidomycosis. 635 86

We describe the case of a 58-year-old man who presented to the hospital with central abdominal pain, nausea, fever, chills, and dyspnea. While in the hospital, jaundice appeared and the liver function tests revealed features of both cholestasis and hepatocellular injury. He developed gram-negative septicemia and died on the sixth hospital day. Autopsy disclosed a perforated terminal ileal diverticulum and a contiguous mesenteric abscess. There was also severe phlebitis of mesenteric venous radicles which extended superiorly to the intrahepatic portal venules and veins. The portal veins were surrounded by multiple hepatic abscesses that varied in size from microscopic to 2.5 cm. This appears to be the first report in the world literature of suppurative pylephlebitis and hepatic abscesses resulting from a perforated ileal diverticulum. The subject of small bowel non-Meckelian diverticulosis is reviewed because of the rarity of this condition and the diagnostic challenges it poses.
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PMID:Perforated diverticulum of the terminal ileum. A previously unreported cause of suppurative pylephlebitis and multiple hepatic abscesses. 642 54

Teroxirone is a novel triepoxide, synthesized as an alkylator and showing a broad spectrum of preclinical activity. It has good cytotoxic activity against sublines of P388 and L1210 leukemias resistant to another alkylating agent, cyclophosphamide. Thirty-six patients received teroxirone as a single iv push for 5 sequential days every 4 weeks. The dose-limiting toxic effects were phlebitis and cutaneous "flare" reactions, with a maximal tolerated dose of 340 mg/m2/day X 5. Nausea, vomiting, and myelosuppression were present but were not dose-limiting at the maximal tolerated dose. This dose would probably be a reasonable dose for phase II trials, but could not be delivered repeatedly without a central line. Since the local reactions were very severe and unique, we believe that studies on the safety of repeated administration via a central line should be completed in animals before trials of systemic therapy in humans begin.
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PMID:Phase I trial of teroxirone. 647 50

Twenty-two patients who had metastatic breast cancer previously treated with combination chemotherapy, cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or CMF with vincristine and prednisone, were treated with Carminomycin (carubicin) 20 mg/m2 body surface area by intravenous bolus injection once every 3 weeks. Of 21 evaluable patients, 1 patient achieved complete remission, 5 patients achieved partial responses, and 11 remained stable. Cases of acute drug toxicity included myelosuppression, phlebitis, and gastrointestinal symptoms; there were four cases of mild alopecia, which consisted of thinning of the scalp hair. There were three cases of biopsy-proven cardiomyopathy, contrary to previous reports from the United Soviet Socialist Republic, which indicated that this drug was relatively free of cardiotoxicity. The median duration of remission for responders was 23 weeks. It is believed that Carminomycin has significant activity against metastatic breast cancer and, because its side effects, especially nausea, vomiting, and alopecia, were considerably milder than those experienced with Adriamycin, further investigation of this drug is warranted.
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PMID:Carminomycin. A new anthracycline analog in the treatment of advanced breast cancer. 654 98

Marcellomycin is a new anthracycline that was proposed for clinical trials on the basis of experimental data suggesting reduced potential for hematologic and cardiac toxicity as compared to conventional anthracyclines. This phase I trial was designed to determine the maximum tolerated dose of marcellomycin at a single-dose schedule. The drug was given as a 15-to 30-min i.v. injection. Eighteen patients with a variety of solid tumors received a median of 2 courses (range: 1-5) at doses of 5-60 mg/m2. Myelosuppression was dose-limiting and somewhat unpredictable. It was characterized by early thrombocytopenia and late leukopenia. It occurred at doses greater than or equal to 40 mg/m2 and resulted in a few cases of infection and hemorrhage. Nausea, vomiting and stomatitis were frequent and occasionally severe. Other common non-hematological toxic effects consisted of local phlebitis and fatigue. Electrocardiographic changes were also encountered. Hair loss was rare and negligible. No antitumor activity could be detected. It appears that phase II trials should be preferably restricted to ambulatory patients and that a dose schedule of 50 mg/m2 repeated every 3 weeks may be proposed for this favorable patient population.
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PMID:Clinical phase I trial of marcellomycin with a single-dose schedule. 668 82

The pharmacology, chemistry, pharmacokinetics, clinical studies, and adverse effects of amsacrine, an investigational antineoplastic agent, are reviewed. Amsacrine's mechanism of action is not clearly understood, although the drug is known to inhibit DNA synthesis. As an investigational NCI "Group C" agent, amsacrine is available to physicians for the treatment of adult patients with refractory acute nonlymphocytic leukemia (ANLL) under an established protocol. Following intravenous administration, amsacrine has a biphasic plasma clearance. It is extensively metabolized by the liver to inactive compounds that are excreted in the bile. Phase I studies indicated that amsacrine was potentially effective in patients with solid tumors and acute leukemias. Patients with solid tumors could tolerate much lower doses of amsacrine than leukemia patients because of dose-limiting bone-marrow suppression in the former. In Phase II studies, amsacrine appeared effective in treating the acute leukemias, with response rates of 31% and 23% for acute lymphocytic leukemia and ANLL, respectively. Patients with other types of cancers have not responded to amsacrine therapy. Frequently occurring adverse effects of amsacrine include leukopenia and thrombocytopenia in patients with solid tumors; nausea, vomiting, and diarrhea; mucositis in patients receiving higher doses (leukemia patients); alopecia; hepatotoxicity; and phlebitis. The clinical usefulness of amsacrine appears limited to treatment of the acute leukemias. Studies of combination therapies that include amsacrine are currently underway and should further define the therapeutic role of amsacrine.
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PMID:Review of amsacrine, an investigational antineoplastic agent. 676 91

A phase II study of KW2083 [7-N-(p-Hydroxyphenyl)-Mitomycin C], a derivative of Mitomycin C, was carried out in 20 patients with carcinoma of the lung and in 19 patients with metastatic pulmonary tumor. KW2083 was administered by single intravenous injection at a dose of 20-30 mg/m2 weekly or a single 70 mg/m2 dose. Patients treated with a dose of 20-30 mg/m2 should be given at least 3 doses for eligibility. Of 17 evaluable patients with carcinoma of the lung (11 adenocarcinomas, 3 squamous cell carcinomas, 2 small cell carcinomas and 1 large cell carcinoma), two patients with adenocarcinoma showed a partial response (11.8%). Two patients who achieved PR had adenocarcinoma without prior therapy received KW2083 at a single dose of 70 mg/m2 Objective response rates were 18.2% for 11 patients with adenocarcinoma and 25% for 8 patients with adenocarcinoma treated with a single dose of 70 mg/m2 of 15 evaluable patients with metastatic pulmonary tumor, no patients showed any objective responses. The hematologic toxicities were thrombocytopenia (less than 5 X 10(4)/mm3, 41.6%) and leukocytopenia (less than 2000/mm3, 28.1%); it was observed in 19% of the patients, that thrombocytopenia continued for more than 6 weeks after stopping therapy. Gastrointestinal symptoms such as anorexia (81%), nausea (66%) and vomiting (16%) were severe in patients treated with a single dose of 70 mg/m2. Fever in 19%, alopecia in 13%, phlebitis in 9%, eruption in 6%, stomatitis in 6% and liver insufficiency in 13% were also observed.
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PMID:[Phase II study of KW2083 [7-N-(p-hydroxyphenyl)-mitomycin C] in patients with carcinoma of the lung and metastatic pulmonary tumor]. 688 1


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