Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We performed a phase I study of menogaril to determine if dosage reduction was required in patients with hepatic dysfunction and if the relationship between pharmacokinetics and leukopenia, previously defined in patients with normal hepatic and renal function, was altered. Eighteen patients received 27 courses of menogaril, of which 26 were evaluable for toxicity. Patient characteristics were median age, 63 years (range, 28-80 years), 14 male/4 female, and median Karnofsky performance status 80% (range, 60-100%). Prior therapy included none, five; chemotherapy only, seven; radiotherapy only, two; and chemotherapy and radiotherapy, four. Menogaril was administered as a 2-h.i.v. infusion every 28 days at 62.5 (one patient), 125 (eight patients), 187.5 (seven patients), and 250 mg/m2 (six patients), based on pretreatment serum bilirubin, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Patients also had indocyanine green and antipyrine clearances measured before menogaril treatment. Menogaril and metabolites were assayed by high performance liquid chromatography. Dose-limiting toxicity was leukopenia. WBC nadirs occurred between days 8 and 20 (median, 15). Three patients developed platelet nadirs below 100,000/microliters. Other toxicities included grade I nausea and vomiting in three patients and phlebitis at the site of drug infusion in six patients. Correlations were defined between pretreatment indocyanine green clearance and serum concentrations of alkaline phosphatase and total bilirubin. There were no correlations between pretreatment serum concentrations of bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, indocyanine green clearance or antipyrine and menogaril clearances. Menogaril pharmacokinetics in patients with elevated liver function tests was indistinguishable from that described in patients with normal liver function tests. There were excellent correlations between plasma area under the curve of menogaril and the percentage decreases in WBC and neutrophils. These were well described by two models previously used to study the same relationships in patients with normal hepatic and renal function. When compared to previous studies, patients with hepatic and renal dysfunction had a greater percentage decrease in WBC for any given area under the curve than did patients with normal hepatic and renal function. On the other hand, there was no difference in the relationship between percentage decrease in neutrophils and menogaril area under the curve in these two groups of patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Phase I study and pharmacokinetics of menogaril (NSC 269148) in patients with hepatic dysfunction. 295 59

GR-C507/75 (GR38032F) antagonizes the 5-HT3 (serotonin) receptor and prevents cisplatin-induced emesis in animals. In this dose-ranging trial, 44 patients with cancer receiving chemotherapy known to produce nausea and vomiting (including cisplatin, cyclophosphamide, and doxorubicin) received three intravenous (IV) infusions of GR-C507/75 every two hours beginning 30 minutes before chemotherapy. Ten dosage levels were explored, ranging from 0.04 mg/kg to 0.35 mg/kg in each of the three infusions. Toxicities were mild and included sedation, dizziness, headache, transient elevations of SGOT or alanine aminotransferase (ALT), and dry mouth. No akathisia or acute dystonic reactions were observed. Antiemetic effects were seen in patients receiving cisplatin at 120 mg/m2. GR-C507/75 can be safely administered on this schedule at IV dosages up to 0.35 mg/kg in patients receiving chemotherapy. Further studies of this agent at higher dosages and by different schedules are appropriate.
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PMID:Dose-ranging evaluation of the serotonin antagonist GR-C507/75 (GR38032F) when used as an antiemetic in patients receiving anticancer chemotherapy. 296 55

A clinical phase II study of recombinant human leukocyte interferon A (rIFN-alpha A, Ro 22-8181) for various skin malignant tumors was jointly conducted at nine medical institutes across the country in order to study its clinical effect and side effects. Patients received Ro 22-8181 alone in doses ranging from 3 X 10(6) U/day to 50 X 10(6) U/day either by intramuscular injection or by local injection. Good response was obtained in one (4.8%) of 21 patients treated by intramuscular injection and in 26 (72.2%) of 36 patients treated by local injection. The percentage of good responses achieved by local injection for individual diseases was 55.6% (5/9) for metastatic malignant skin melanoma, 100% (11/11) for cutaneous malignant lymphoma, 100% (5/5) for extramammary Paget's disease, 75% (3/4) for intraepidermal cancer and 50% (2/4) for metastatic skin cancer. Main side effects were fever, anorexia, general fatigue, chills, nausea and vomiting. Abnormal laboratory data included leukopenia, and elevation of GOT and GPT, although their incidence was lower with local injection than with intramuscular injection. Side effects were mostly improved by reduction of the dose or discontinuation of the treatment.
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PMID:[Phase II study of recombinant leukocyte A interferon (Ro 22-8181) in skin malignant tumors]. 298 7

Fundamental and clinical studies of a new carbapenem antibiotic, imipenem/cilastatin sodium (MK-0787/MK-0791), were carried out to evaluate the drug in treating infections of the female genital organs. The following results were obtained: In 4 patients undergoing hysterectomy, the penetration of MK-0787 and MK-0791 into female genital organ tissues was studied following a 30-minute intravenous drip infusion of MK-0787/MK-0791 500 mg/500 mg. Plasma levels of MK-0787 and MK-0791 in cubital venous blood following the drip infusion peaked at 0 minute with values of 51.2 micrograms/ml and 61.9 micrograms/ml, respectively, then decreased to 1.9 micrograms/ml and 0.7 microgram/ml, respectively, at 201 minutes. MK-0787 penetrated readily to female genital organ tissues and levels of the drug exceeded 0.5 approximately 1.9 micrograms/g in various organ tissues at 201 minutes following an intravenous drip infusion of 500 mg/500 mg of MK-0787/MK-0791. Clinically, MK-0787/MK-0791 was used for the treatment of obstetrical and gynecological infections at a dosage of 500 mg/500 mg twice daily by intravenous drip infusion. Clinical effects of MK-0787/MK-0791 were analyzed in 22 patients, including 9 patients with intrauterine infections, 7 with intrapelvic infections, 5 with adnexitis, and 1 with an external genital infection. Excellent responses were seen in 5 patients (22.7%), good responses in 15 (68.2%), and poor responses in 2 (9.1%). The efficacy ratio was 90.9%. After the treatment, 15 out of 18 isolates were eradicated for an 83.3% eradication rate. All strains of S. epidermidis (2 strains), Eubacterium lentum (1 strain), Peptococcus sp. (1 strain), beta-Streptococcus (1 strain), Gram-positive rods (2 strains), Enterobacter cloacae (1 strain), Bacteroides bivius (1 strain), Pseudomonas sp. (1 strain), Pseudomonas cepacia (1 strain) and Gram-negative rods (1 strain) were eradicated by the MK-0787/MK-0791 treatment. The safety of the drug was analyzed in 22 patients, effects occurred in 3 (13.6%). Among those 3 patients, diarrhea occurred in 1 patient, rash in another and nausea and vomiting in yet another. One patient had an increased BUN after the MK-0787/MK-0791 treatment. In the other 21 patients, no abnormalities in creatinine, GOT, GPT, or T. Bil. values were observed. It may be concluded that MK-0787/MK-0791 is useful for the treatment of obstetrical and gynecological infections.
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PMID:[Fundamental and clinical studies of imipenem/cilastatin sodium in the field of obstetrics and gynecology]. 346 86

Fundamental and clinical studies were performed by our study group to evaluate the usefulness of the combination (1:1) of imipenem (MK-0787), a carbapenem antibiotic, and cilastatin sodium (MK-0791), an inhibitor of dehydropeptidase-I, in the treatment of patients with obstetric and gynecologic infections. The following results were obtained. Antimicrobial activities of MK-0787 were tested with inocula of 10(6) cells/ml of organisms isolated from patients with obstetric and gynecologic infections. Peak MIC's of MK-0787 were less than or equal to 0.20 micrograms/ml for S. aureus, less than or equal to 0.20 micrograms/ml for S. epidermidis, 1.56 micrograms/ml for E. faecalis, 0.39 micrograms/ml for E. coli, less than or equal to 0.20 micrograms/ml for K. pneumoniae and less than or equal to 0.20 micrograms/ml for B. fragilis. When 0.5 g/0.5 g of MK-0787/MK-0791 was administered by a 30-minute intravenous drip infusion, maximum concentrations of MK-0787 in all female genital tissues were obtained at the end of the infusion, and Cmax ranged from 9.4 micrograms/g to 17.0 micrograms/g. In addition, the maximum concentration of MK-0787 in pelvic dead space exudate was 13.2 micrograms/ml at 88 minutes after the start of the infusion. The penetration of MK-0787/MK-0791 into female genital tissues and dead space exudate was found to be good and sufficient to cover MIC's against organisms isolated from patients with obstetric and gynecologic infections. Clinical efficacy was evaluated in 201 evaluable patients out of a total of 253 patients with obstetric and gynecologic infections. Clinical responses were excellent in 2, good in 181 and poor in 18 patients, and the efficacy rating was 91.0 percent. Efficacy ratings classified by types of infections were 93.2% (82/88) for intrauterine infections, 83.0% (39/47) for intrapelvic infections, 100% (26/26) for adnexitis, 90.0% (18/20) for infections of the external genital organs and 90.0% (18/20) for other infections. Side effects were observed in 6 of the 253 patients; rash in 4, nausea and vomiting in 1 and diarrhea in 1 patient. Abnormal laboratory findings were observed in 10 of the 253 patients; elevation of GOT, GPT, LDH and Al-P in 1, elevation of GOT, GPT and Al-P in 1, elevation of GOT and GPT in 4, elevation of GPT in 1, elevation of BUN in 1, increase of eosinophiles in 1, decrease of segmented neutrophils in 1 patient.
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PMID:[Fundamental and clinical studies of imipenem/cilastatin sodium in the field of obstetrics and gynecology. Study group of imipenem/cilastatin sodium in the field of obstetric and gynecological infections]. 353 68

Ceftizoxime (CZX) was used for 33 patients with respiratory tract infections; 22 patients with pneumonia, 3 patients with pulmonary abscess, 4 patients with diffuse panbronchiolitis and 4 patients with acute exacerbation of bronchiectasia. Clinical effects of CZX were evaluated in 33 patients; excellent in 16 and good in 14 patients. The efficacy rate was 91%. Bacteriological effects of CZX were prominent in 7 patients infected with S. pneumoniae, H. influenzae, K. pneumoniae and Citrobacter, but not in a patient infected with P. aeruginosa. The elimination rate was 92% (12/13). As the side effects, exanthema in 1 patient and gastrointestinal symptoms (nausea and vomiting) in 1 patient were observed. However, they improved without any treatment by cessation of CZX use. Abnormal laboratory findings were observed in 2 patients with elevated GOT and/or GPT. They normalized after cessation of drug. The usefulness of CZX was 82% (27/33). Therefore, CZX is a very useful drug and its effects are promising in clinical management of respiratory tract infections.
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PMID:[Evaluation of ceftizoxime in the treatment of respiratory tract infections]. 386 81

A cooperative study was carried out in 32 institutions throughout the country to evaluate the clinical efficacy of recombinant human leukocyte A interferon (rIFN-alpha A, Ro 22-8181) on malignant tumors of the urogenital tract. The responses were evaluated according to the "Criteria for the Evaluation of Clinical Effects of Cancer Chemotherapy on Solid Tumor" proposed by Koyama and Saito. Out of 269 cases which were examined in the present study, 138 cases were evaluable. Among 108 cases with renal cell carcinoma, efficacy was observed in 15 cases; complete response (CR) in 2 cases and partial response (PR) in 13 cases, indicating an efficacy rate of 13.9%. PR was obtained in 1 case out of 14 with bladder cancer and 1 case out of 6 with tumors of the renal pelvis and ureter. Main subjective and objective adverse reactions observed were fever, malaise, anorexia and nausea and/or vomiting. Laboratory test abnormalities consisted of leukopenia, thrombocytopenia and elevation of GOT X GPT. All of these disappeared with discontinuation of rIFN-alpha A or after administration of its therapeutic dose.
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PMID:[Clinical efficacy of recombinant human leukocyte A interferon (rIFN-alpha A) on malignant tumors of the urogenital tract]. 388 63

Renal arterial embolization is often used in the treatment of patients with renal cell carcinoma, either preoperatively to facilitate nephrectomy or as palliative therapy in advanced cases. Eighteen patients (18/58; 31%) underwent renal arterial embolization in our department since 1979, initial 10 cases with Gelfoam and steel coil (group G) and recent 8 cases with absolute ethanol (group A). Clinical studies of daily changes of symptoms and blood chemistry in both groups after embolization were compared and the results were as follows: Severe flank pain was noted immediately after embolization but thereafter well controlled without analgesics in group A. The patients in group G experienced no pain during the procedure of embolization but have had moderate flank pain of two or three days' duration with nausea and/or vomiting and required surgical procedure within a few days after embolization. Post embolization fever in group A was described as higher than that in group G significantly. Leukocytosis was noted to be persistent for up to seven days and blood chemistry showed transient marked elevations of GOT, GPT and LDH immediately after the procedure without significant value in both groups. Embolization to advanced tumor with many parasitic vessels or massive local invasion may not always be available for remaining of viable-appearing tumor cells in venous lumen, as if palliative treatment. Absolute ethanol may be more useful as the embolizing substance than Gelfoam and steel coil by reason of producing wide severe infarction of diseased kidney. Broad marked infarction due to renal arterial embolization may make pathological diagnosis difficult. Immunological effects of renal arterial embolization were not observed in short term patients survival.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Renal arterial embolization for renal cell carcinoma]. 402 78

Cefotaxime (CTX) was microbiologically and clinically studied in surgery. CTX shows excellent antibacterial activity in vitro against Gram-negative bacilli including E. coli. Klebsiella spp., and Proteus spp. in comparison with cefmetazole (CMZ) and cefazolin (CEZ). Antibacterial activity of CTX is found to be superior to that of CEZ and equal to that of CMZ against Gram-positive bacteria (S. aureus and S. epidermidis). The antibacterial activity of CTX against anaerobic bacteria exceeds that of CEZ and almost equal to that of CMZ. It also showed minimum inhibitory concentration values which, clinically speaking, offer great expectation. CTX is also superior to CMZ and CEZ in its antibacterial activity against P. aeruginosa. Clinical studies were carried out in the group A for which CTX was administered a drug of first choice for postoperative infections in surgery, and in the group B for which CTX was administered as a drug of second choice since the antibiotic of first choice had been ineffective for these cases. As a result, high effective rates were obtained in both groups (80.3% for the group A, and 77.1% for the group B). With reference to the group B, an effectiveness rate of 100% was obtained for the cases in which CEZ had been ineffective and 55.6% was obtained for 10 cases in which mainly combination of CMZ had been ineffective. Side effects appeared in 3 cases (1 case each of tinnitus and malaise, vomiting and nausea, and fever) with an incidence rate of 1.46%. Abnormal clinical laboratory findings appeared in 4 cases (1 case each of leukopenia and increase in GOT and GPT; eosinophilia; increases in platelet and monocyte; and increases in GOT, GPT and A1-P) with an incidence rate of 1.95%.
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PMID:[Evaluation of cefotaxime for postoperative infection in surgery]. 609 87

Ceftazidime has been evaluated in a total of 1548 cases of infection involving medical and surgical patients. Most of the cases were treated with 1 to 2 g/day. Of the total number of assessable cases (1418), over 80% responded satisfactorily (1141). Bacterial eradication was achieved in 850 cases (81% of those assessable). The incidence of adverse events was low (2.1%) being observed in 32 cases out of 1529 that were assessable. Clinical events were mainly skin eruptions, nausea and vomiting. Laboratory abnormalities were mainly slight elevations of serum GOT, GPT, alkaline phosphatase and eosinophil counts.
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PMID:Clinical evaluation of ceftazidime in Japan. 622 60


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