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)

Clinical efficacy of IPM/CS against urinary tract infections (UTI) was evaluated on 19 patients with malignancies (bladder tumor: 15, prostate cancer: 3, uterus cancer: 1) and 1 patient with a benign disorder (ureter stenosis) who had undergone ureterocutaneostomy between January, 1988 and December, 1990. Their ages ranged from 42 to 79 years. Postoperatively, they had UTI with pyuria of greater than or equal to 5/hpf and bacteriuria of greater than or equal to 10(4)/ml. IPM/CS was administered at a dose of 0.5 g (0.25g/0.25 g) twice a day through intravenous drip infusion. Its efficacy was evaluated according to the UTI criteria for clinical evaluation as ruled by the Japanese Society of Chemotherapy. Overall clinical value was rated "excellent" in 4 (20%), "moderate" in 9 (45%) and "poor" in 7 (35%) cases for a total of 65%. The efficacy by types of infection was 33% and 70.6% in the group of single infection and in the group of mixed infection, respectively. As to bacteriological efficacy 34 of the 38 strains (89.5%) isolated were eradicated following its administration. The eradication rate was 84.6% for P. aeruginosa, and 84.6% for E. faecalis. Microbes which appeared after its dosing amounted to 6 classes of 17 strains, 6 NFB strains of which were identified. As a side effect, elevation of serum GPT (5%) was noted. Regardless of the underlying conditions (malignant diseases and ureterocutaneostomy), clinical efficacy of IPM/CS was appreciable. In addition, the MIC for (P. aeruginosa, E. faecalis) of IPM/CS was lower than that of PIPC.
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PMID:[Clinical studies of efficacy of imipenem/cilastatin sodium against urinary tract infections with ureterocutaneostomy]. 152 97

A phase II study on recombinant human leukocyte A interferon (rIFN-alpha A) was carried out in 30 patients with urogenital cancers. Each patient received rIFN-alpha A by i.m. injection every day for at least 4 weeks. The initial daily dose was 3 X 10(6) U, being escalated at intervals of 3 days or more up to 50 X 10(6) U. The results are summarized as follows: In aged patients, the daily dose appropriate for everyday i.m. injection was considered to be 9 X 10(6) U or below, judging from the adverse reactions observed. According to Koyama and Saito's response criteria, partial response (PR) and minor response (MR) were obtained, respectively, in 3 and 1 out of 12 patients with renal cell carcinoma, while PR was seen in 1 out of 9 with urothelial cancer. No response was observed in patients with testicular cancer and in those with prostatic cancer. Various kinds of adverse reactions were recognized and each patient showed one reaction or more. Fever, fatigue, leukopenia, anemia, thrombocytopenia and elevation of GOT and GPT were observed relatively frequently. Among these, fatigue and thrombocytopenia were regarded as dose limiting factors.
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PMID:[Phase II study of recombinant human leukocyte A interferon on urogenital cancer patients]. 400 82

Recently, cases of liver damage and liver tumors have been reported after treatment of prostate cancer patients with the antiandrogen cyproterone acetate (CPA). In rat liver, CPA initiates a wave of DNA synthesis that is accompanied by apoptosis. In apoptotic hepatocytes, a latent form of transforming growth factor beta 1 (TGF-beta 1) is detectable by immunohistochemistry. Injection of a single dose of TGF-beta 1 induces apoptosis in the liver of animals pretreated with CPA but has an insignificant effect in untreated animals. In this study, we show by Northern analysis that there is increased expression of TGF-beta 1 in the liver after CPA treatment. Detection of TGF-beta 1 with in situ hybridization showed that TGF-beta 1 was synthesized in the parenchymal cells. Time course and dose-response experiments performed 48 hours after the last application of CPA showed that apoptotic nuclei with chromatin condensed at the nuclear periphery (AN) were already visible 2 hours after injection (0.13%), and apoptotic bodies (ABs) increased 2 to 9 hours after the injection (from 1.28% to 6.67%) after 25 micrograms TGF-beta 1/kg. At 4.5 hours after injection, an induction of apoptosis could be detected with 0.25 microgram TGF-beta 1/kg and after the maximum dose (250 micrograms TGF-beta 1/kg) ANs (0.24%) and ABs (16.74%) were homogeneously distributed throughout the liver lobe. Irrespective of the dose or time after injection of TGF-beta 1, 82% of the ABs were localized within hepatocytes. Liver enzymes were detected in high amounts in the serum (eightfold elevation of glutamate dehydrogenase, fivefold elevation of alanine transaminase [ALT]) 7 hours after the first visible sign of apoptosis. After an additional 20 hours, the liver contained many necrotic figures. These results suggest that the combination of TGF-beta 1 expression coupled with a strikingly enhanced sensitivity to the induction of apoptosis could be responsible both for the liver damage and the development of liver tumors observed after treatment with CPA.
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PMID:The antiandrogen cyproterone acetate induces synthesis of transforming growth factor beta 1 in the parenchymal cells of the liver accompanied by an enhanced sensitivity to undergo apoptosis and necrosis without inflammation. 859 60

A phase I study (open trial) of bicalutamide (Casodex), a non-steroidal antiandrogen, was conducted on 16 patients with prostatic cancer (stage C to D). The patients were given 10, 30, 50, 80 or 100 mg of bicalutamide orally daily for 12 weeks. Adverse reactions were observed in 8 out of 16 patients, but almost all were mild. Breast pain, gynecomastia and hot flushes were observed in 6 patients. Adverse reactions regarding liver function tests were observed in 3 patients. These were increased glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), alkaliphosphatase (AL-P) or gamma guanosine 5'-triphosphate (gamma-GTP). However, during or after the treatment period the elevated values were reversed to the pretreatment level. In terms of efficacy, anti-tumor effect was observed in 1 or 2 patients at each dose. Serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol increased during treatment. Plasma concentrations of the R (-) enantiomer, which has antiandrogenic activity, reached the steady state 6-8 weeks after the initiation of treatment; its apparent plasma elimination half-life observed following repeated administration was 8.4 +/- 1.1 days. In conclusion, bicalutamide (10-100 mg od) is considered to be tolerated well enough to be administered to patients with prostatic cancer and has shown evidence of anti-tumor effect.
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PMID:[Phase I study of bicalutamide (Casodex), a nonsteroidal antiandrogen in patients with prostatic cancer]. 871 91

Flutamide is a nonsteroidal antiandrogen agent. Since it was marketed in February of 1989 in the USA for treatment of prostate cancer, its potential for hepatotoxicity has been reported in Western countries. Here we report the case of a 72-year-old patient who suffered from general malaise, poor appetite, nausea and jaundice after six months of flutamide therapy for the treatment of prostate cancer. He had no past history of liver disease and was not receiving other medications. Liver biochemistries revealed elevated serum alanine aminotransferase and aspartate aminotransferase concentrations of up to 1,035 U/l and 745 U/l, respectively. Serum total bilirubin concentration was elevated to 7.0 mg/dl. Serologic markers for acute viral hepatitis were all negative. Serum antinuclear antibody, antimitochondrial antibody and antismooth-muscle antibody were also negative. Percutaneous liver biopsy revealed pericentral zonal necrosis with bridging hepatic necrosis. The patient's clinical symptoms and signs began to improve after discontinuation of flutamide, and his liver function had returned to normal three months later. Roussel Uclaf causality assessment for adverse drug reaction confirmed the diagnosis of drug-induced liver injury. This case reminds us that patients who are receiving flutamide should be regularly monitored for liver function. If drug-induced liver injury is suspected, flutamide must be discontinued promptly to avoid progression of liver injury.
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PMID:Flutamide-induced liver injury: a case report. 987 26

A seventy-three year-old patient with prostate cancer underwent radical prostatectomy, followed by total androgen brocking therapy using flutamide and LH-RH agonist. As Hepatic dysfunction (GPT = 3.045 IU/l) was noticed by periodic blood analysis, flutamide was stopped and he was hospitalized immediately without any subjective symptoms. Ten days after the admission, he developed massive bleeding from duodenal ulcer, resulting in duodenal perforation. Following the emergency operation, plasma exchange therapy was repeated against serious hepatic dysfunction. However, he was dead of pneumonia two months after the admission. Autopsy revealed biliary congestion in a small liver, although it was not cirrhotic. In our patient, hepatic dysfunction was irreversible and prolonged. We strongly recommend to perform serial liver function test from the start of treatment with flutamide, especially during the initial three months. Flutamide should be stopped promptly it significant liver abnormalities are detected.
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PMID:[Fatal hepatic failure following hepatitis caused by flutamide: a case report]. 1038 60

Severe hepatotoxicity occurred in a prostate cancer patient treated with 375 mg of flutamide per day, 125 mg three times a day, for 11 weeks. Serial measurements of serum concentrations of flutamide and its metabolites in the patient showed an unusually high serum level and delayed elimination of flutamide and suggested decreased metabolic activity of oxidation of flutamide to OH-flutamide. In 37 patients with prostate cancer we periodically monitored the serum concentrations of flutamide as well as liver function parameters. In 2 patients, glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) elevated over 100 IU/L, and treatment with flutamide was discontinued. Slight elevation of GOT and GPT over 40 to 100 IU/L was also detected in 5 patients, and flutamide was withdrawn. The elevated GOT and GPT in these 7 patients recovered to the pretreatment levels after discontinuation of the treatment. In these patients with flutamide-induced hepatic disorders, the average serum concentration of flutamide was higher (2.76 times, and that of OH-flutamide was lower (0.76 times), as compared with patients who maintained normal liver function.
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PMID:[Flutamide-induced hepatic disorder and serum concentrations of flutamide and its metabolites in patients with prostate cancer]. 1065 14

To prevent treatment withdrawal due to flutamide-induced liver dysfunction, we performed maximum androgen blockade (MAB) therapy by combining a luteinizing hormone-releasing hormone agonist or orchiectomy with low-dose flutamide (125 mg x 2/day) in patients with prostate cancer. In this study, the efficacy, adverse effects such as hepatotoxicity, and compliance were compared retrospectively between 35 patients who received low-dose flutamide therapy (1995-1999) and 27 patients who received flutamide at its ordinary dose (125 mg x 3/day). No significant difference was observed in the response rate (> or = PR) as determined from the prostate-specific antigen parameter (p = 0.6211) or the incidence of hepatotoxicity based on the aspartate aminotransferase and alanine aminotransferase levels. However, flutamide withdrawal due to liver dysfunction was less frequent in the low-dose group (2.9%) than in the ordinary dose group (18.5%) (p = 0.0386). MAB therapy using low-dose flutamide is expected to prevent the reduction in the compliance due to side effects and to improve the long-term prognosis in patients with prostate cancer, who are mostly elderly individuals.
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PMID:[Clinical efficacy of treatment with low-dose flutamide in maximum androgen blockade therapy]. 1141 Oct 99

The caffeine test measures the activity of cytochrome p450 (CYP1A2) which is a major enzyme involved in the activation of flutamide. The usefulness of this test in predicting flutamide-induced hepatic injury in patients with prostate cancer was examined. The subjects were: (1). five patients whose aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level rose to 100 IU/l or higher following the start of flutamide (moderately injured group); (2). four patients whose AST and ALT levels were higher than normal but less than 100 IU/l (mildly injured group); and (3). two patients whose hepatic function remained normal (normal group). The subjects were each given canned coffee to drink. Urinary caffeine (137X), paraxanthine (17X) and 1, 7-dimethyluric acid (17U) levels were measured 4-5 h later. The metabolite ratio, (17U+17X)/137X, was calculated to serve as an indicator of CYP1A2 activity. The metabolite ratio for the moderately injured group (3.98+/-1.56) and the mildly injured group (5.55+/-1.42) were lower than that for the normal group (9.56). The results suggest that a decrease in CYP1A2 activity is involved in the onset of flutamide-induced hepatic injury, and that the caffeine test seems to provide a useful means of its prediction.
Prostate Cancer Prostatic Dis 2002
PMID:Caffeine test in predicting flutamide-induced hepatic injury in patients with prostate cancer. 1249 2

An examination of the change in plasma concentration of OH-flutamide in low-dose flutamide (250 mg/day) monotherapy for 5 prostate cancer patients was performed. We treated 5 patients diagnosed with prostate cancer between September and November 2002. The plasma concentrations of OH-flutamide, PSA and AST/ALT were measured before and after low-dose flutamide monotherapy was started. The plasma concentrations of OH-flutamide were stable in the third day after medication was started, and even when compared with the plasma concentrations of OH-flutamide 375 mg/day, there was no significant difference. Although at the observation period was short, PSA fell favorably in all patients. The AST/ALT were in the normal range in all patients. The low-does flutamide therapy has been one of medical treatments if its safety and effectiveness has been demonstrated.
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PMID:[Examination of the change in plasma concentration of OH-flutamide in low-dose flutamide (250 mg/day) monotherapy for prostate cancer patients]. 1504 44


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