Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

An investigation was carried out to determine the therapeutic effect of panipenem/betamipron (PAPM/BP), a injectable carbapenem antimicrobial agent, on infections in pregnant women during perinatal period. Of the 41 patients enrolled in the study, 34 were subjected to the analysis, with 1 exemption because of protocol violations (regimen), 3 because of uncertain evidence symptoms of infection, and 3 because of failure to undergo laboratory tests. PAPM/BP was administered by intravenous drip infusion at doses of 0.5 g twice or three times a day daily for periods of 3 to 14 days. The efficacy rate according to the evaluation of the Drug Efficacy Evaluation Committee and the attending physicians was 79.4% (27/34), with 49 of the 61 clinical isolates (80.3%) being eradicated. Safety was evaluated as "safe" in 39 of the 41 assessable patients (94.1%). Mild headache and nausea were experienced by 1 patient (2.4%) as adverse drug reactions, but the symptoms disappeared after the completion of treatment. Slight elevations of GOT, GPT and LDH in laboratory tests were observed in 1 patient (2.4%), but these values returned to normal after the completion of treatment. These results suggested that PAPM/BP may be a useful drug in the treatment of bacterial infections during the perinatal period. To firmly establish its safety, however, further clinical and pharmacokinetic studies are needed in larger populations.
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PMID:[Study on the therapeutic effect of panipenem/betamipron on perinatal infection in pregnant women]. 1020 85

The purpose of the study was to evaluate the efficacy and safety of tacrine over 30 weeks in Chinese patients with probable Alzheimer's disease (AD). A total of 100 patients with mild to moderate AD were recruited and randomly assigned to active or placebo treatment. The active group received 30 mg/day of tacrine for the first 6 weeks, 60 mg/day for the next 6 weeks, 90 mg/day for 6 more weeks and then 120 mg/day for the remaining 12 weeks. Safety evaluations included biweekly determinations of alanine aminotransferase (ALT). The primary outcome measures were Cognitive Abilities Screening Instrument (CASI), Clinical Global Impression of Change (CGIC) by investigator and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Secondary outcome measures were Mini-mental State Examination (MMSE), Alzheimer's Deficit Scale (ADS) and CGIC by caregivers. Sixty-eight patients were included in an intent-to-treat analysis (48 active and 20 placebo); 56 patients had evaluable data at week 30 (36 active and 20 placebo). The results of the complete case analysis revealed a significant improvement in the CASI and MMSE scores of the active group in the 18th week (90 mg/day) and the 30th week (120 mg/day) (p < 0.01). In the intent-to-treat analysis, significant improvement of the active group was noted on CASI at week 30 (p = 0.05), but there was no significant difference in the measures of IQCODE, CGIC and ADS. The primary reasons for withdrawal of tacrine-treated patients (39 patients, 52%) were asymptomatic ALT elevation, anorexia and nausea/vomiting. These patients all recovered from the adverse events on discontinuation of treatment. Tacrine produced a statistically significant improvement in the CASI and MMSE in Chinese patients with mild to moderate AD using a lower dose than in western people.
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PMID:A double-blind, placebo-controlled study of tacrine in Chinese patients with Alzheimer's disease. 1036 47

We carried out a multiple-center study, including a double-blined randomized clinical trial on fluconazole (Flu, group A) and ketoconazole (Keto, group B) and an open trial on Flu only for evaluating the efficacy and safety of Flu in treating deep and shallow fungal infection. 222 patients participated in the study and most of them had severe underlying diseases. The dosage and therapeutic duration were as follows: Flu 200-400 mg daily for 1-8 weeks in 34 patients with fungal infection and 150 mg as a single dose in 30 patients with fungal vaginitis; Keto 400 mg daily for 1-8 weeks in 30 patients with fungal diseases and for 5 days in 30 patients with fungal vaginitis. In the trial 124 patients were randomized to receive either Flu (64 patients) or Keto (60). The cure rate in group A and B was 81.3% (52/64) and 58.0% (35/60) respectively (P < 0.05). The fungal eradication rates of the two groups were 85.7% and 70.0% (P > 0.05) respectively. 98 patients entered the open trial. They included fungal infection of the respiratory tract and urinary tract, cryptococal meningitis, fungal sepesis and systemic dissemination of mycosis and fungal vaginitis. 84 (85.7%) were cured. The fungal eradication rate of this group was 92.9%. The side-effect rates of the three groups were 3.1% (2/64), 5.0% (3/60) and 6.1% (6/98) respectively. They were mild and transient vomiting, nausea, and anorexia. In group B and the open group however, there was one case of ALT elevation in each group (P > 0.05). This study suggests that Flu is a safe, effective and useful drug for the treatment of severe fungal infection.
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PMID:[Fluconazole versus ketoconazole in systemic fungal infection: a double-blind randomized study]. 1037 74

Docetaxel has been reported to show promising anti-tumour activity in pancreatic ductal cancer (PC). This study was conducted to evaluate the activity and toxicity of moderate-dose (60 mg m(-2)) docetaxel in Japanese chemo-naive patients with measurable metastatic PC. The patients had a performance status of 0-2. They received docetaxel intravenously over a 1- to 2-h period without any premedication for hypersensitivity reactions. This treatment was repeated every 3-4 weeks with dose adjustments based on the toxic effects observed. Twenty-one patients were eligible and treated with docetaxel. The median number of courses was 2 (range, 1-4). None of the patients achieved an objective response; seven showed no change and 13 showed progressive disease. In one patient, the response was not assessable because of early death. The median survival time for all patients was 118 days. The main grade 3-4 toxicities by patient were leucocytopenia (67%) and neutropenia (86%). Other grade 3-4 toxicities included anaemia (10%), thrombocytopenia (5%), nausea/vomiting (29%), anorexia (29%), GOT/GPT increase (10%), alkaline phosphatase increase (14%), malaise/fatigue (33%) and alopecia (24%). In conclusion, docetaxel, administered on this schedule, did not show significant anti-tumour activity in patients with metastatic PC.
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PMID:Phase II study of docetaxel in patients with metastatic pancreatic cancer: a Japanese cooperative study. Cooperative Group of Docetaxel for Pancreatic Cancer in Japan. 1040 50

The safety and tolerability of quinupristin/dalfopristin were assessed in both comparative and non-comparative trials (2298 quinupristin/dalfopristin-treated patients). In comparative clinical trials, the most frequent systemic adverse events related to quinupristin/dalfopristin were nausea (4.6%), diarrhoea (2.7%), vomiting (2.7%) and skin rash (2.5%). The comparator group showed similar rates, except that nausea was significantly more common (7.2%; P = 0.01). In non-comparative trials, arthralgia and myalgia were reported most frequently but were reversible upon treatment discontinuation. The renal, inner ear, cardiovascular and central nervous systems were not implicated as significant target organs for toxicity. The most frequent local adverse events related to infusion of quinupristin/dalfopristin were inflammation, pain, oedema, infusion site reaction and thrombophlebitis. Results of laboratory tests while on therapy were comparable for quinupristin/dalfopristin and comparator groups, except that increases in conjugated bilirubin of >5 x the upper limit of normal were reported in 5.5% of quinupristin/dalfopristin recipients; increases in total bilirubin of >5 x the upper limit of normal occurred in 1.5%. Comparator recipients more frequently had increases in alanine aminotransferase and alkaline phosphatase. Quinupristin/dalfopristin inhibits the cytochrome P450 3A4-mediated metabolism of drugs including midazolam, nifedipine, terfenadine and cyclosporin. Therefore, plasma drug monitoring and/or dosage reduction of these agents is prudent. Concomitant administration of drugs that can prolong the electrocardiographic QTc interval should be avoided. Quinupristin/dalfopristin is visually and chemically compatible with commonly used drugs of various classes, but it is not compatible with sodium chloride solution and certain other drugs, including some antimicrobials. Therefore, when prescribing quinupristin/dalfopristin, clinicians should be aware of the potential for peripheral venous intolerance, arthralgias and myalgias, increases in conjugated bilirubin, interactions with drugs metabolized by the cytochrome P450 3A4 isoenzyme and certain physico-chemical incompatibilities. However, multiple studies have shown that the safety and tolerability of quinupristin/dalfopristin are generally favourable, and that it provides clear benefits to ill patients with severe gram-positive infections.
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PMID:Safety and tolerability of quinupristin/dalfopristin: administration guidelines. 1051 96

To evaluate the safety, toxicity, and maximum tolerated dose (MTD) of IFN beta-1a (Rebif, Serono Laboratories, Inc.) in patients with malignant diseases unresponsive to standard therapies and to assess the pharmacodynamics and pharmacokinetics associated with IFN beta-1a administration, an open-label, single-center phase I study was designed. Thirty-four patients were enrolled and treated with IFN beta-1a. All had measurable solid neoplasms or evaluable hematological malignancies. All patients received a single i.v. bolus dose of IFN-beta-1a on day 1, followed 7 days later by daily s.c. injections for 28 consecutive days. Successive groups of three patients received increasingly higher doses (in geometric progression from 1.5 million international units (MIU)/m2 to 24 MIU/m2) until dose-limiting toxicities were noted. Pharmacokinetic and biological studies, including measurement of the activity of 2',5'-oligoadenylate synthetase (2',5'-OAS) in peripheral blood mononuclear cells and serum levels of soluble Tac (CD 25) and beta-2 microglobulin, were performed on patients who agreed to participate. i.v. and s.c. doses of IFN beta-1a up to 24 MIU/m2 were administered. The most frequent adverse events (AEs) were constitutional symptoms. Grade III AEs during i.v. dosing included fever, elevation of bilirubin, and infection unrelated to therapy. No grade IV events were seen. AEs noted during continuous s.c. therapy included fever, liver transaminase increase, albuminuria, fatigue, nausea, myalgia, and rigors. Dose-limiting toxicities were encountered during s.c. dosing at the 24-MIU/m2 and 18-MIU/m2 dose levels and included gastrointestinal toxicity, elevations of aspartate aminotransferase and alanine aminotransferase, and albuminuria. The s.c. MTD was determined to be 12 MIU/m2, although there was great variability in the individual patient's ability to tolerate IFN beta-1a. 2',5'-OAS activity, thought to be indicative of IFN activity, increased within hours after i.v. and s.c. dosing, with the level remaining persistently elevated during the s.c. daily injections. The highest peak level was attained in the 6-MIU/m2 group. There was no evidence that the increase in 2',5'-OAS activity decayed with repetitive dosing, nor was there evidence of accumulation in this pharmacodynamic marker. Serum beta-2-microglobulin levels showed a modest time- and dose-dependent increase after s.c. administration of IFN beta-1a, with the largest increase seen at the 24-MIU/m2 dose level. There were no clear dose-dependent responses noted in soluble Tac serum levels. IFN beta-1a was well-tolerated when administered by a single i.v. bolus injection at doses up to and including 24 MIU/m2. Daily s.c. injections for at least 28 days were well-tolerated at doses up to and including 12 MIU/m2, with some patients tolerating doses twice as high as this. The MTD for the i.v. route could not be clearly determined according to the guidelines of the protocol. However, i.v. bolus doses up to 24 MIU/m2 were relatively well-tolerated. For the s.c. route, the MTD was determined to be 12 MIU/m2, but there was great interpatient variability, with some patients able to tolerate higher doses.
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PMID:A phase I study of recombinant interferon-beta in patients with advanced malignant disease. 1063 30

Twenty-four patients with chronic hepatitis B virus (HBV), antibody to hepatitis B e antigen (anti-HBe), HBV DNA positivity, and alanine transaminase (ALT) elevation who failed previous interferon alfa (IFN-alpha) therapy were included in a pilot study of combination therapy with ribavirin and IFN-alpha. The patients received daily oral ribavirin (1,000-1,200 mg according to body weight) plus 5 million units (MU) IFN-alpha2b three times a week for 12 months and were followed-up for 12 months. The median viremia level decreased significantly at the end of treatment (1.2 x 10(3) copies/mL) and follow-up (4.0 x 10(2) copies/mL) compared with the baseline (3.0 x 10(6) copies/mL; P <.05). After 12 months, 8 of 24 (33%) patients had cleared HBV DNA and 12 (50%) had normal ALT levels. At the end of the study virological and biochemical response was 50% and 21%, respectively. Thus, virological and biochemical response sustained in 5 of 24 (21%) patients retreated with ribavirin and IFN-alpha; none of them lost hepatitis B surface antigen (HBsAg). Liver histology improved in 2 of 4 sustained responders but in none of the 12 nonresponders with paired biopsies (P =.05). The response was independent of dose and duration of previous treatment, viral load, or the distribution of HBV precore wild-type/mutant variants. However, sustained responders had significantly higher necroinflammation (P =.036) and fibrosis (P =.007) scores. IFN-alpha-related side effects were mild and reversible on discontinuation. In 4 (17%) patients who suffered nausea and diarrhea the ribavirin dosage was reduced by 50% after 1 month of therapy and finally discontinued in all of them. No patient had liver disease decompensation. In summary, combination therapy with ribavirin and IFN-alpha may be efficacious to treat viremic anti-HBe-positive patients with chronic hepatitis B who have failed previous IFN therapy.
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PMID:Pilot study of combination therapy with ribavirin and interferon alfa for the retreatment of chronic hepatitis B e antibody-positive patients. 1065 77

We conducted a multicenter phase II clinical study of fludarabine phosphate, a new purine nucleotide analogue, in patients with chronic lymphocytic leukemia (CLL). Fludarabine phosphate was administered at a dose of 20 mg/m2/day intravenously for 5 days every 4 weeks as one course. Six courses as a maximum were repeated. The response rate was 38.5% (95% confidence intervals: 20.2% to 59.4%), with 1 complete remission and 9 partial remissions out of 26 treated patients. Major drug-related adverse reactions were fever, nausea, weakness, and paresthesia of the fingers; as a grade-3 reaction, varicella was also reported. Neutropenia and thrombocytopenia were observed as manifestations of hematologic toxicity. Clinical laboratory test results revealed abnormalities in hepatic function, including increased GPT, but none of these was rated grade 3 or 4.
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PMID:[Phase II clinical study of SH L 573 (fludarabine phosphate) in patients with chronic lymphocytic leukemia]. 1065 76

In previous trials, the orally active iron chelator deferiprone (L1) has been associated with sporadic agranulocytosis, milder forms of neutropenia and other side-effects. To determine the incidence of these events, we performed a multicentre prospective study of the chelator. Blood counts were performed weekly, and confirmed neutropenia mandated discontinuation of therapy. Among 187 patients with thalassaemia major, the incidence of agranulocytosis (neutrophils < 0.5 x 109/l) was 0.6/100 patient-years, and the incidence of milder forms of neutropenia (neutrophils 0.5-1.5 x 109/l) was 5.4/100 patient-years. All cases of neutropenia resolved after interruption of therapy. Neutropenia occurred predominantly in non-splenectomized patients. Nausea and/or vomiting occurred early in therapy, was usually transient and caused discontinuation of deferiprone in three patients. Mild to moderate joint pain and/or swelling did not require permanent cessation of deferiprone and occurred more commonly in patients with higher ferritin levels. Mean alanine transaminase (ALT) levels rose during therapy. Increased ALT levels were generally transient and occurred more commonly in patients with hepatitis C. Persistent changes in immunological studies were infrequent, although sporadic abnormalities occurred commonly. Mean zinc levels decreased during therapy. Ferritin levels did not change in the overall group but decreased in those patients with baseline levels > 2500 microgram/l. This study characterized the safety profile of deferiprone, and, under the specific conditions of monitoring, demonstrated that agranulocytosis is less common than previously predicted.
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PMID:Safety profile of the oral iron chelator deferiprone: a multicentre study. 1069 60

The toxicity of isoniazid chemoprophylaxis was assessed in 83 health care workers (HCWs) receiving a 6-month course, in whom clinical toxicity and liver function were monitored. Thirty-four HCWs (41%) developed an adverse event; in 26 (76%), toxicity was sufficiently severe to require cessation of treatment. Of the total, liver function test abnormalities (serum alanine transaminase levels more than two times normal) were evident in 14 subjects, with 8 requiring cessation of therapy. Other symptoms reported included malaise, nausea with associated anorexia, arthralgia, and rash. Mean time to development of symptoms was 3 weeks (range, 0.5-6 weeks), with the mean age of those with toxicity not differing significantly from those without (38 vs. 39 years). The high rate of toxicity seen in this study is sufficiently notable that we advocate the use of monthly liver function testing and frequent review in those receiving isoniazid prophylactic therapy.
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PMID:Isoniazid toxicity in health care workers. 1082 56


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