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)

Gemcitabine (GEM) is a novel deoxycytidine analogue which has shown promising antitumor activity in solid tumor models and a broad range of schedule-dependent MTDs (12-4560 mg/m2) in preliminary clinical studies. The present phase I trial evaluated escalating doses of weekly GEM using a 30-min infusion at a starting dose-level of 300 mg/m2/wk x 3 every 28 days. At least 3 patients entered each dose-level step and 3 more cases were treated when significant toxicity was seen. A total of 39 patients with various advanced solid tumors and prior chemotherapy entered this study. Six escalation steps (102 courses) were tested to define the MTD at 1,370 mg/m2/wk. No definite dose-effect relationships were observed for myelosuppression up to 1,095 mg/m2/wk. However, increased severity of leucopenia (dose-limiting) and greater non-hematologic toxicity as well as a higher number of toxic treatment delays, requiring subsequent dose attenuation in 6 out of 12 patients, were observed at 1,370 mg/m2/wk. In all, 6 out of 11 patients experiencing WHO grade > or = 3 toxicity (11/21 events recorded in 11/18 courses) were treated at the MTD. Clinically significant toxicity included (patients with WHO grade 2-3): leucopenia (44%), thrombocytopenia (26%), anemia (23%), fever (69%), emesis (38%) and AST/ALT rise (26%). Mild proteinuria, ankle edema, skin rash, hair loss and mucositis were seen in < or = 5%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Weekly gemcitabine in advanced or metastatic solid tumors. A clinical phase I study. 786 Feb 27

A study of the clinical profile of 59 patients who presented with hepatitis A virus infection showed that dark urine, fatigue, gastrointestinal complaints, and fever were the most common presenting symptoms. The most frequent physical findings were hepatomegaly and jaundice. The mean presenting laboratory tests included total bilirubin of 5 mg/dL, alkaline phosphatase of 269 units/L, and serum aspartate aminotransferase and alanine aminotransferase levels of 1442 mIU/mL and 1952 mIU/mL, respectively. Atypical manifestations included relapse, cholestasis, rash, and arthralgia. Two patients presented with hepatitis A and concomitant type I autoimmune chronic hepatitis, and both required immunosuppressive therapy. Five patients who presented with hepatitis A were pregnant, and during follow-up, none of their infants developed elevated serum transaminase values or had detectable IgM anti-HAV antibody. All 59 patients experienced complete clinical and biochemical recovery within 6 months after onset of illness.
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PMID:Clinical manifestations of hepatitis A: recent experience in a community teaching hospital. 787 41

A 31-year-old women with chronic active hepatitis B (HBs antigen-positive, HBe antigen-negative) developed a painful petechia rash on both lower legs and the inner surface of the thighs. Histology of a skin biopsy revealed leucocytoclastic vasculitis. The affected skin areas contained HBs antigen and immunoglobulins. Immunosuppressive treatment with initially 60mg/d prednisolone improved the skin condition but activated the chronic hepatitis, GPT rising up to 240 U/l. The steroid treatment had to be discontinued. Subsequently the transaminases became normal but the vasculitis foci recurred. The patient was therefore given alpha-interferon, three times 5 mill. IU weekly subcutaneously for 6 months. The skin lesions disappeared and the circulating HBV-DNA decreased. But the HBs antigen could not be eliminated. It is to be noted that 12 months after the end of the alpha-interferon treatment the vasculitis has not recurred. - This case and published reports indicate that interferon treatment is effective against HBV-associated and immunoglobulin-complex mediated disease.
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PMID:[Hepatitis-B-associated vasculitis. Clinical course with glucocorticoid and alpha-interferon therapy]. 792 48

The efficacy, safety and usefulness of murine anti-endotoxin monoclonal IgM antibody "E5, an intravenous dose of 2 mg/kg" were evaluated in 88 patients with suspected Gram-negative sepsis from 37 institutes in Japan. Out of these, 74 patients were evaluable for the efficacy, 85 for safety and 75 for clinical usefulness. In assessing the efficacy, the patients were divided into 3 groups based on the plasma endotoxin levels (Endospecy with new PCA treatment of plasma): H group with a level of above 9.8 pg/ml and M group with a level of 3.0-9.8 pg/ml and L group with a level of below 3.0 pg/ml. 1. The efficacy rates as assessed following administration of E5 were 73.1% in the H group, 70.4% in the M group and 38.1% in the L group being higher in the groups with significantly high plasma endotoxin levels. 2. In both the H and M groups in whom plasma endotoxin levels were significantly high, the majority of the patients showed rapid reduction of the levels after administration of E5. 3. In all groups, improvement in body temperature, pulse rate, blood TNF-alpha and blood IL-6 was observed after treatment with E5. In the H and M groups with an endotoxin level of > or = 3.0 pg/ml, improvement in platelet count as well as in CRP was noted. The H group showed also improvement in WBC. 4. Improvement in the shock score was noted in all the groups but was more outstanding in the H and M groups in the early stage of treatment. 5. Side effects were seen in 5 (5.9%) of 85 patients and all thought to be allergic in symptoms such as rash, itching, fever and flare. 6. The reaction to the prick test performed before administration of E5 was negative in all these 5 patients. For 3 of the 5 patients, anti-E5 IgE antibody was measured. In all of them, the IgE levels were higher than those of healthy controls. Also, in 47.6% of patients, an elevation of anti-E5 IgG antibody was noted two weeks after the administration. 7. Clinical laboratory abnormalities were observed in 3 (3.5%) of 85 patients. They were an elevation of S-GOT.S-GPT and lowering of BUN, increased Al-p and decreased CH50, increased neutrophilia (%) and were all slight in the degree of the changes. 8. The clinical usefulness of E5 was evaluated for 75 patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Phase II study of edobacomab (E5) in the treatment of gram-negative sepsis]. 813 82

The cause of fulminant hepatic failure is reported to be unknown in more than half the cases in Japan. We recently reviewed 23 cases of fulminant hepatic failure that had been treated at our hospital. The cause of disease had been regarded as unknown before this study. It was found that seven of these patients had been under ecarazine hydrochloride therapy when they developed fulminant hepatic failure. We examined the reasons why fulminant hepatic failure in these seven patients had not been previously attributed to ecarazine, and found that it could be explained by the following factors: (1) the time from the start of ecarazine therapy to the onset of hepatic failure was long; (2) in all cases, hepatic failure developed more than 10 days after the clinical recognition of hepatitis; and (3) characteristic signs of drug-induced hepatic failure such as a skin rash and positive lymphocytes stimulation test with the drug were absent in all cases. Fulminant hepatic failure in these cases could be characterized by: (1) rapid decrease in serum alanine transaminase (ALT) level after discontinuation of ecarazine, (2) prolonged jaundice despite discontinuation of ecarazine, (3) high incidence of anti-nuclear antibody (ANA) (57%), and (4) histological findings of extensive hepatocellular necrosis ranging from bridging necrosis to massive necrosis. Of the seven patients, four died of fulminant hepatic failure. These four patients had received high doses of ecarazine hydrochloride for prolonged periods. Our data suggest that there may be many cases in which the cause of fulminant hepatic failure or acute hepatitis was not previously determined that can be attributed to long-term drug therapy for chronic diseases.
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PMID:Fulminant hepatic failure caused by ecarazine hydrochloride (a hydralazine derivative). 861 25

We report the case of a 28-year-old-prostitute from Thailand with HIV infection stage B2 associated with retroperitoneal lymph node tuberculosis. 6 days after the beginning of anti-tuberculous therapy (isoniazid, rifampicin, pyrazinamid and ethambutol) the temperature rose to 40.5 degrees C, diarrhea, vomiting, and tachycardia developed and systolic blood pressure fell to 80 mm Hg. Liver function tests revealed acute hepatic failure (ALT 800 IU/l rising to 1500; serum bilirubin 89 mumol/l rising to 238.0; alkaline phosphatase 199 IU/l; glucose 1.8 mmol/l; prothrombin time 20%). Isoniazid, rifampicin, and pyrazinamid were replaced by streptomycin and PAS. A few days after withdrawal the liver profile returned to normal. Hours after the reintroduction of rifampicin total body erythema, pruritus, vomiting and severe hypotension developed, requiring saline methylprednisolone and epinephrine administration. The next reexposure to intravenous rifampicin produced a rash and was rapidly discontinued. Liver function tests remained normal. Later mild adverse reactions to streptomycin and pyrazinamid occurred, two drugs which had been well tolerated before. Subsequently the diagnosis of adrenal insufficiency was established. After initiation of steroid replacement (50 mg prednisolone) the antituberculous therapy with isoniazid, pyrazinamid and ethambutol was well tolerated. We conclude that the shock in this HIV-infected patient was either due to severe anaphylaxis to rifampicin or acute adrenal insufficiency ensuing on this drug. The reversible fulminant acute hepatic failure represents either an adverse effect of antituberculous drugs, especially hepatotoxic interactions of drug combinations, or an ischemic liver injury during hypotension caused by anaphylaxis. The case illustrates the complex nature of side effects of antituberculous drugs in HIV patients and their aggravation by adrenal insufficiency.
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PMID:[Fulminant, rapidly reversible hepatitis and life-threatening anaphylaxis following rifampicin in an HIV-positive female patient with latent adrenal cortex insufficiency]. 864 39

An investigation was made into pharmacokinetics and clinical effects of the newly-developed cephem antibiotic for injection, cefozopran (SCE-2787, CZOP), in pediatric patients. In 26 patients in whom pharmacokinetics were investigated, peak serum concentrations of CZOP administered at doses of 10, 20 and 40 mg/kg by i.v. injection were 21.3 +/- 10.0 (mean +/- standard deviation), 51.0 +/- 9.9 and 68.3 +/- 0.7 micrograms/ml, respectively. Serum concentrations at 6 hours after administration were 2.9 +/- 1.7, 2.3 +/- 0.9 and 4.6 +/- 2.6 micrograms/ml, with the levels roughly above MIC90s for dominating pathogenic bacteria being maintained until 6 hours after treatment. Urine concentrations were in the range between 200 and 560 micrograms/ml at 4 to 6 hours after dosing. Cumulative urine excretion accounted for 70 to 80% of dose. In 11 patients in whom pharmacokinetic investigations were performed, peak serum concentrations of CZOP administered at doses of 10, 20 and 40 mg/kg by 30-min. i. v. drip infusion were 37.1, 66.3 +/- 25.5 and 95.7 +/- 8.9 micrograms/ml, respectively. Serum concentrations at 6 hours after dosing were 1.6, 2.3 +/- 0.8 and 3.0 +/- 0.4 micrograms/ml, respectively, with the levels above MIC90s for dominating pathogenic bacteria also being maintained until 6 hours after administration. Urine concentrations were 190 micrograms/ml or more until 8 hours after dosing and the cumulative urinary excretion accounted for 50 to 70% of dose. In 9 patients with meningitis in whom CZOP penetration into cerebrospinal fluid was investigated, concentrations in the fluid of the compound i.v. injected at doses from 40 to 53 mg/kg were in the range between 1.6 and 43.4 micrograms/ml exceeding MICs for pathogenic bacteria at 1 to 1.5 hours after dosing. In all of the 38 patients in whom pharmacokinetic investigations and clinical evaluations were performed, CZOP was good to excellent (excellent in 22 patients and good in 16 patients). Also in bacteriological evaluations, all of the 31 strains of investigated pathogenic bacteria were eradicated. The clinical efficacy rates for the 335 subjects for clinical evaluations were 97.0% (195/201) for patients in whom pathogenic bacteria were detected (group A), and 95.5% (128/134) for patients in whom no pathogenic bacteria were detected (group B). In bacteriological evaluations, the eradication rates of Gram-positive and Gram-negative bacteria were 96.3% (77/80) and 94.5% (155/164), respectively, with the eradication rate in total being 95.1% (232/244). Safety investigations were performed in 364 patients. Adverse reactions were reported in 11 patients (3.0%), including diarrhea (aqueous stool and soft stool) in 7 patients (1.9%) and drug rash (rash, eruption and wheal) in 4 patients (1.1%). Abnormal laboratory test values were noted in 54 patients, including eosinophilia in 20 patients (6.3%) and elevated GPT in 20 patients (6.3%). The adverse reactions and abnormal laboratory test values were not serious, disappearing or improving during the continued treatment period or as a result of discontinuation of the treatment. Serum and urine concentrations of CZOP, when administered by i.v. injection and 30-min, i.v. drip infusion at doses of 10, 20 and 40 mg/kg, were higher than the MICs for pathogenic bacteria until 6 hours after dosing. The drug also showed favorable penetration into cerebrospinal fluid. It was therefore considered that CZOP was a highly useful drug for the treatment of pediatric infections with sufficient bacteriological and clinical efficacy when administered at a dose of 40 to 80 mg/kg three to four times daily.
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PMID:Pharmacokinetics and clinical effects of cefozopran in pediatric patients. 885 4

A 33-year-old man presented malar rash in April, 1992. The rash had gradually developed and he was admitted to our hospital in February, 1994. Laboratory findings showed proteinuria of 0.5-0.8 g/ day, thrombocytopenia (4.8 x 10(4)/mm3), false positive serologic test for syphilis, anti-nuclear antibody with a speckled type at a titer of 1 : 80. Activated partial thromboplastin time was prolonged (41.3 s), and anti-beta 2-GPI antibody was strongly positive (56.6 U/ml on enzyme linked immunosorbent assay). The diagnosis of systemic lupus erythematosus with antiphospholipid syndrome was made and prednisolone 60 mg/day improved his manifestations. He could be discharged in July, 1994. Nine months after the discharge he developed dyspnea, and he was admitted to our hospital again. On admission the blood pressure was 212/170 mmHg, Levine III/VI systolic murmur was noted at the apex of heart. Significant laboratory findings showed as follows: WBC 15, 110/mm3 (Neu 73%, Lym 18%), RBC 380 x 10(4)/mm3, Hb 10.2 g/dl, Plt 20.0 x 10(4)/mm3, GOT 23 IU/l, GPT 21.
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PMID:[Acute cardiac failure due to dilated cardiomyopathy in systemic lupus erythematosus with antiphospholipid antibody]. 912 25

A 60-years-old male subject, who had complained of swallowing difficulties, was diagnosed as having cancer of the esophagus. No allergic reaction was noted in his history. Mechanical anastomosis connecting the gastric tract with the cervical esophagus was performed satisfactorily. During the operation, haemodynamics remained stable and in the absence of excessive bleeding, 5 bags of fresh frozen plasma were used. One day after the operation, however, marked abnormalities in liver function were observed and by the 11th day GOT and GPT levels had increased to 783 and 1,108, respectively. In addition, redness suggestive of drug rash was observed. Although steroid therapy, followed by plasma exchange therapy, was repeated four times, the patient died on day 21. Autopsy revealed that the patient suffered an acute form of fulminant hepatitis. Viral infection, drug treatment or surgical aggression is often considered to be the cause of this condition. In this subject, it is thought that the hepatic disorder was evoked by either the operation or drug treatment and that subsequently allergic reaction or immune abnormality caused the fulminant hepatitis.
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PMID:[A case of cancer of the esophagus accompanied by postoperative fulminant hepatitis]. 930 3

Efficacy and safety of a newer injectable cephalosporin, cefluprenam (CFLP) on cases with bacterial pneumonia and chronic respiratory tract infections were evaluated at a dose of 1g (potency), d.i.d for 7 days. 1. Of 130 cases in total, 116 cases were enrolled for the clinical efficacy evaluation. The efficacy rate (excellent and good responses) was 94.8% (110/116). The efficacy rate was 93.8% (60/64) for cases with bacterial pneumonia, and 96.2% (50/52) for cases with chronic respiratory tract infections. The recurrence was noted in 1.2% (1/82). The bacteriological response rate was 100.0% (32/32) for gram positive cocci, 93.8% (15/16) for gram negative rods and 97.9% (47/48) in total. 2. Adverse drug reactions were noted in 3.9% (5/129), consisting of 2 cases with skin rash, 1 case with drug fever, 1 case with skin rash and skin itching and 1 case with drug fever and headache. The abnormal laboratory changes were noted in 23.6% (30/127), mainly containing the elevation in GPT and GOT, and eosinophylia. The safety rate (no problem evaluation) was 74.8% (95/127). 3. The usefulness rate (very useful and useful evaluations) was 93.1% (108/116). As suggested by the evaluation on the secondary endpoint in the phase III comparative studies with both bacterial pneumonia and chronic respiratory tract infections, it was confirmed that the 7 day therapy of CFLP was promising for treatment of moderate bacterial pneumonia and chronic respiratory tract infections, because the high clinical efficacy was obtained and also the incidence of allergic reactions with CFLP was almost the same as that of ceftazidime (CAZ) evaluated highly safe. Based on these results, it was concluded that CFLP was useful in the management of moderate respiratory tract infections and also the recommended therapeutic period with CFLP was within 7 days.
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PMID:[Usefulness of 7 day therapy with cefluprenam in the management of respiratory tract infections]. 931 Nov 95


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