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)

10-Edam (10-ethyl-10-deaza-aminopterin), an antifolate derivative, was administered to 14 chemotherapy-naive patients with advanced colorectal carcinoma. The drug was given weekly by intravenous route at an initial dose of 80 mg/m2, with escalation or attenuation according to tolerance. Mucositis was dose limiting and occurred in 11 of 14 patients (78.6%). Removal from the study was required in one patient due to progressive pulmonary fibrosis that was histologically identical to methotrexate-induced lung damage. Toxicity was otherwise mild to moderate and included diarrhea, constipation, abdominal discomfort, anorexia, nausea/vomiting, rash, and fatigue. There were no responses to 10-Edam in this study, 95% confidence interval (0-0.23). Stable disease was achieved in four patients; the remaining 10 patients demonstrated progression within 9 weeks of initiating systemic therapy. 10-Edam employed at this dosage and schedule was not effective as a treatment against advanced colorectal carcinoma.
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PMID:Phase II trial of 10-Edam in patients with advanced colorectal carcinoma. 230 19

The results of a serosurvey of Oklahomans for the presence of antibody to Ehrlichia canis is reported. Paired serum specimens, from patients lacking the serologic criteria for diagnosis of Rocky Mountain spotted fever (RMSF), were tested. A four-fold increase in E. canis-IFA antibody was found in 16/144 (11 percent) of these paired serum samples. Patients with serologic evidence of E. canis infection had a mean age of 34 years, 69 percent were male, and 63 percent lived in a town less than 10,000 population. Signs and symptoms included: fever 94 percent, headache 94 percent, fatigue 94 percent, anorexia 81 percent, nausea 60 percent, and rash 44 percent. When compared to control patients, whose sera were submitted for RMSF testing but did not meet serologic criteria for RMSF or E. canis, case-patients were more likely to have had leukopenia (OR = 4.9, 95 percent Cl = 1.2, 19.0) and tick exposure (OR = 9.5, 95 percent Cl = 1.4, 62.7). The results suggest E. canis, or a closely related agent, is a cause of human illness. Ticks are probable vector.
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PMID:Epidemiologic and clinical characteristics of persons with serologic evidence of E. canis infection. 231 66

Brequinar sodium is a quinoline carboxylic acid derivative that has shown antitumor activity in a number of in vivo murine and human tumor xenograft models. Its mechanism of action is blockade of de novo pyrimidine biosynthesis by inhibition of dihydroorotic acid dehydrogenase. In vitro and in vivo studies demonstrate the superiority of prolonged drug exposure in achieving tumor growth inhibition. This phase I study evaluated the administration of brequinar sodium by short, daily i.v. infusion for 5 days repeated every 4 weeks. Fifty-four subjects were enrolled in the study and received drug in doses ranging from 36-300 mg/m2. The dose-limiting toxicities were mucositis and diffuse skin rash. Other toxicities included myelosuppression, nausea, vomiting, malaise, and burning at the infusion site. The maximum tolerated dose on the "daily times 5" schedule was 300 mg/m2. The recommended phase II dose is 250 mg/m2. Pharmacokinetic analysis of the day 1 drug clearance curves in 51 subjects showed slight nonlinearity in the relationship between dose and area under the clearance curve (AUC). The dose versus AUC relationship was well described using a Michaelis-Menten model of brequinar elimination kinetics with Vmax = 45 (micrograms/ml)/h and Km = 123 micrograms. Analysis of the day 5 drug clearance curves revealed a diminution in Vmax to 30 (micrograms/ml)/h. As a consequence of the reduction in Vmax brequinar plasma concentrations on day 5 were higher than predicted from day 1 drug kinetics. Pharmacodynamic analysis of the day 1 kinetic parameters and the toxicities occurring during the first cycle of drug therapy revealed significant correlations between mucositis and dose, AUC, and peak brequinar concentration; between leukopenia and AUC and peak drug concentration; and between thrombocytopenia and beta elimination rate.
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PMID:Phase I and pharmacokinetic study of brequinar sodium (NSC 368390). 236 34

A phase I trial of 2-beta-D-ribofuranosylthiazole-4-carboxamide (NCS 286193, tiazofurin) was conducted using a 5-day i.v. bolus schedule, every 21 days. Thirty one patients with advanced cancer were entered on the trial. A total of 106 cycles were administered with doses ranging from 550 to 2750 mg/m2. Concomitant administration of Allopurinol was necessary to prevent hyperuricemia. Tiazofurin was difficult to evaluate and many side effects were variable and sporadic. The dose limiting toxicities were nonhematologic consisting particularly of myalgias, headaches and general malaise. Other toxicities included nausea, vomiting, stomatitis, lethargy, sleeping difficulty, sinus bradycardia, skin rash, desquamation of the palms and soles, photophobias and burning of the eyes. Hematologic toxicity was mild and not dose related though it led to a neutropenic septic death in one patient at 2750 mg/m2. Anemia was documented in 60% of cycles. Biochemical abnormalities consisted of mild hyperglycemia, hyperuricemia and elevated skeletal creatinine phosphokinase levels which did not correlate with the incidence or degree of myalgias. Though some patients were able to tolerate higher doses, the recommended dose for phase 2 study is 1650 mg/m2. Further studies will be required to achieve a better understanding of this interesting drug.
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PMID:Phase I study of tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, NSC 286193). 238 15

Twenty-three patients with squamous cell carcinoma were treated with a combination chemotherapy consisting of cisplatin, vincristine, and peplomycin. Overall response rate was over 70% including complete disappearance of tumors in one patient. Peplomycin was given by continuous i.v. or s.c. infusion using a micro-infusion pump. All the patients experienced some degree of nausea, vomiting, and hair loss. Phlebitis and induration of injection sites with subsequent local pigmentation were frequently encountered. Nausea and vomiting were caused mainly by cisplatin, but more than 60% of the patients experienced transient increase of anorexia or nausea in the period of peplomycin administration. Eruption with skin excoriation or pigmentation along scratch dermatitis were seen in 5 patients. These side effects were well tolerated, and high fever which is commonly observed in one-shot therapy did not develop in any patient. Pulmonary fibrosis was also not seen. Peplomycin should be given by low-dose continuous infusion because of its low toxicity and comparable antineoplastic activity to one-shot therapy.
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PMID:[Side effects of peplomycin]. 242 49

Fusidic acid has previously been noted to prevent syncytial formation by human immunodeficiency virus (HIV) in vitro. Since this drug is a cheap, usually well-tolerated substance with known toxicity profile, an open, uncontrolled trial was undertaken to evaluate its possible efficacy in HIV disease. Twenty HIV antibody positive patients (10 with AIDS and 10 with ARC) were treated with sodium fusidate 500 mg every 8 h for up to 3 months. One patient died during therapy and six ceased treatment due to adverse events. Rash, nausea, diarrhea, and/or abdominal pain caused difficulties in all patients. There was no significant improvement in clinical state or T-helper cell levels, and no observed decrease in HIV p24 antigen during treatment. We conclude that in this open trial, sodium fusidate had no observable beneficial clinical, virological, or immunological effects.
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PMID:Clinical, immunological, and virological effects of sodium fusidate in patients with AIDS or AIDS-related complex (ARC): an open study. 249 93

A total of 65 patients with food allergy which manifested primarily by disorders of the gastrointestinal tract, bronchi and skin were placed under observation. The patients were administered sodium chromoglycate (nalcrom) per os in a dose of 200 mg 4 times a day for 2-3 weeks, in part of cases up to 3 months and even up to 1-1.5 year. The skin manifestations of allergy (pruritus, urticaria, Quincke's edema, and eczematous rash), abdominal pain, diarrhea, vomiting, bronchospasm, rhinitis, and conjunctivitis disappeared. At the same time the majority of the patients demonstrated the reduction of the intensity of skin responses to the administration of different food antigens, the decrease of the antibody titer in blood serum in response to food antigens, and of the IgE content in blood. The side effects (nausea, heartburn, intensification of skin itch and abdominal pain) were noted in 4 cases.
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PMID:[Treatment of patients with food allergy using Nalcrom]. 249 73

An 81-year-old woman had chills, fever, nausea, vomiting, and epigastric pain. On day 3 she had hematuria and was treated with trimethoprim-sulfamethoxazole. On day 5 she had a cough, hypotension, anemia, azotemia, and elevated hepatic enzyme levels. Her condition deteriorated with thrombocytopenia, anuria requiring dialysis, edema, and hypoalbuminemia. Treatment with chloramphenicol and doxycycline was started on day 10. By day 11, she was in hypotensive shock; on day 12 she had seizures and died. Murine typhus was diagnosed by demonstration of antibodies to Rickettsia typhi by indirect immunofluorescence. Necropsy revealed interstitial pneumonia, pulmonary edema, hyaline membranes, alveolar hemorrhages, petechiae and vasculitis in the central nervous system, interstitial myocarditis, multifocal interstitial nephritis and hemorrhages, splenomegaly, portal triaditis, and mucosal hemorrhages in urinary tract. Immunofluorescent R. typhi were demonstrated in the lungs, brain, kidneys, liver, and heart. This unusual death occurred in an elderly patient without rash who was treated too late with antirickettsial drugs.
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PMID:Histopathology and immunohistologic demonstration of the distribution of Rickettsia typhi in fatal murine typhus. 249 81

To evaluate the value of the nonsedative anticonvulsants carbamazepine and valproic acid a controlled study including drug monitoring was carried out. Intoxicated alcoholics (n = 138) were admitted for inpatient detoxication and randomly assigned to either carbamazepine (n = 43), sodium valproate (n = 46) or placebo (n = 49) in a double-blind fashion. Drug treatment lasted for four days and the daily doses of both drugs amounted to 1200 mg in the beginning of the study. Sodium valproate induced gastric distress, nausea and vomiting more frequently than placebo. About half of the subjects had to stop carbamazepine because of intolerable side-effects including vertigo, nausea, vomiting, diplopia and rash. Serum carbamazepine levels (18-89 mumol/l) were found to be high (greater than 40 mumol/l) in many but not all of these subjects. Seizures occurred in 3 subjects on placebo, 2 on carbamazepine and 1 on sodium valproate. Delirium tremens developed in 2 on sodium valproate and 1 on placebo. The study demonstrates that drug side-effects may seriously hamper the utility of carbamazepine and sodium valproate as routine treatment for the prevention of alcohol withdrawal symptoms.
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PMID:Prevention of alcohol withdrawal seizures with carbamazepine and valproic acid. 250 Jan 38

Fourteen patients with refractory metastatic breast cancer were treated with high dose chemotherapy and autologous hematopoietic stem cell rescue. All patients received cyclophosphamide (7.5 g/m2 over 3 days) and thiotepa (150-225 mg/m2 over 3 days), three patients in addition received melphalan (4.5 mg/kg), and seven patients received carmustine (150-562 mg/m2). Toxicities included pancytopenia, infection, hemorrhagic cystitis, skin rash, nausea, vomiting, diarrhea, and mucositis. There was one toxic death secondary to sepsis and ventricular tachycardia. The overall response rate was 77% including a 15% complete response rate. The overall median survival for all patients was 6.0 months (range 2-22 months). The median survival for nonresponders was 3.5 months. The median duration of response was 89 days (range 40-262). In our experience high dose chemotherapy with autologous stem cell reinfusion produces a high response rate in refractory breast cancer. However, because of the short duration of response and overall survival, we feel this type of therapy should be utilized earlier in the course of disease.
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PMID:High dose chemotherapy with autologous hematopoietic stem cell support in the treatment of refractory stage IV breast carcinoma. 250 79


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