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

Three studies of drug toxicity were made in Chinese adults with pulmonary tuberculosis admitted concurrently to short-course antituberculosis regimens. The first was of streptomycin plus isoniazid plus pyrazinamide given daily (SHZ regimen), three times a week (S3H3Z3 regimen) or twice a week (S2H2Z2 regimen). The second was of pyrazinamide in the SHZ regimen and PAS in the standard daily combination of streptomycin plus isoniazid plus PAS (SPH regimen). The third was of the SHZ regimen and these 3 drugs plus rifampicin daily (SHRZ regimen). In study 1 (174 SHZ, 185 S3H3Z3, 182 S2H2Z2 patients), the incidence of arthralgia was associated with the number of doses per week (P less than 0.001). The incidence of other reactions, most of which were cutaneous or vestibular, or symptomless increases in the serum alanine transaminase (AIT) concentration, was similar on all 3 regimens. In study 2 (142 SHZ, 137 SPH patients), hepatic reactions occurred on the SHZ but not on the SPH regimen (P less than 0.002), serum AIT concentrations were distributed over a higher range on the SHZ regimen, and 2 patients had jaundice. Gastrointestinal reactions were more frequent on the SPH regimen (P = 0.06). Arthralgia was commoner on the SHZ regimen (P less than 0.05). In study 3 (38 SHZ, 41 SHRZ patients), the incidence of hepatic reactions, jaundice and arthralgia was similar in the 2 regimens. On the pyrazinamide regimens combined, hepatic reactions were marginally more frequent in patients with Australia antigen or antibody either before or during chemotherapy (P = 0.09). Serum uric acid concentrations were higher in patients on daily than on intermittent pyrazinamide (P less than 0.005), and in patients with arthralgia on the daily pyrazinamide regimen than in matched controls (P = 0.07).
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PMID:Adverse reactions to short-course regimens containing streptomycin, isoniazid, pyrazinamide and rifampicin in Hong Kong. 13 76

Newly diagnosed patients of pulmonary tuberculosis (n = 112) were put on a rifampicin-containing drug regimen. Fifty six patients were also given a placebo tablet twice daily while the other fifty-six were given ranitidine 150 mg twice daily. Gastric pH, gastric emptying time, serum rifampicin levels, urinary total and unchanged rifampicin, serum bilirubin and ALT levels were measured serially. Clinical record of adverse symptoms was maintained. Ranitidine increased the basal as well as post-drug gastric pH without altering the gastric emptying time. Concomitant administration of ranitidine and rifampicin did not alter the absorption, metabolism or excretion of the latter but reduced the frequency of gastrointestinal symptoms.
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PMID:Ranitidine--rifampicin interaction. 148 89

Clinical efficacy and safety of sultamicillin (SBTPC) in patients with lower respiratory tract infections, mainly pneumonia and bronchitis, have been evaluated in a multicenter trial by 19 institutions in the Kyushu area during a period of 12 months from December 1988 to November 1989. 1. Clinical evaluation was made in 132 patients and efficacy rates of SBTPC were 80.0% (28/35) for pneumonia, 78.5% (73/93) for bronchitis and 100% for the remaining 1 patient with other respiratory tract infections. The overall efficacy rate was 79.1% (102/129). 2. Clinical efficacy rate of SBTPC for respiratory tract infections in patients with underlying diseases such as chronic bronchitis, old pulmonary tuberculosis etc., was 75.0% (60/80) which was not significantly different from the efficacy rate of 85.7% (42/49) in patients without underlying diseases. 3. Of 13 patients who failed to respond to previous antibiotic treatments, 8 (61.5%) were effectively treated with SBTPC. 4. Clinical efficacy rates against infections caused by single species of organisms were 90.9% (10/11) for Haemophilus influenzae, 100% (8/8) for Streptococcus viridans and 100% (3/3) for Staphylococcus aureus. The overall clinical efficacy rate in all cases of monomicrobial infections was 88.6% (31/35), in polymicrobial infection 45.5% (5/11) and the overall efficacy rate in cases in which causative bacteria were identified was 78.3% (35/46). 5. Adverse reactions occurred in 6.8% (9/132) of the patients. The symptoms included allergic reaction in 1 patient, gastrointestinal system disorders in 7 patients and general fatigability in 1 patient. As abnormalities in laboratory test values, elevations of A1-P, GOT, and GPT were observed in 3 patients during the study, but returned to normal after discontinuation of SBTPC administration. 6. SBTPC is a useful antibiotic in the treatment of lower respiratory tract infections under the current medical environment where resistant organisms which produce beta-lactamases have been increasing.
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PMID:[Clinical evaluation of sultamicillin in lower respiratory tract infections]. 204 Nov 56

A retrospective study on the evaluation of antituberculous drugs for patients with hepatic dysfunction was undertaken to clarify treatment regimens. The values of GOT, GPT and T. Bil were used as indicators of liver function, and the "deterioration" in the liver function was defined as a level greater than 1.5 times the initial value. Of total 538 cases of active pulmonary tuberculosis, 103 cases (19.1%) had abnormalities in liver functions before chemotherapy, and 21 of 103 cases showed the deterioration in their liver functions during chemotherapy. There was little relationship between the initial status of liver functions and the incidence of their deteriorations after chemotherapy. Nine of 21 cases did not exceed the 3 times of normal ranges of liver functions. These nine cases could tolerate the same regimens of chemotherapy, and showed satisfactory clinical responses to chemotherapy with two exceptions: one died of tuberculosis and the other cerebrovascular disease. On the other hand, of 12 cases with elevated values of hepatic function greater than 3 times the normal limits, 6 cases discontinued chemotherapy. One case, however, died of hepatic failure related to chronic active hepatitis. Eight of 12 cases showed the rapid improvement of liver dysfunctions. These results suggest that antituberculous drugs are acceptable to patients with hepatic dysfunction as long as the elevations of GOT, GPT and T. Bil stay within 3 times of normal limits. Further chemotherapy could be continued under careful monitoring of liver functions even if the cases exhibit elevated levels of liver functions greater than 3 times the normal ranges.
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PMID:[Chemotherapeutic evaluation of pulmonary tuberculosis patients with a complication of hepatic dysfunction]. 205 6

Clinical evaluation, safety and kinetics in serum of sulbactam/cefoperazone (SBT/CPZ) in patients with lower respiratory tract infections have been studied in a multicenter trial participated by 28 institutions in Kyushu area during a period of 13 months from March 1987 to March 1988. 1. Mean peak serum levels of SBT and CPZ in 35 patients up to 4 hours after intravenous infusion of 2 g of SBT/CPZ were 38.2 +/- 17.3 micrograms/ml for SBT and 104.3 +/- 31.4 micrograms/ml for CPZ. Serum half-lives of SBT and CPZ were 0.76 hour and 1.53 hours, respectively. These results were in similar ranges to those reported elsewhere for SBT/CPZ. 2. Serum half-lives of SBT and CPZ after intravenous infusion of 2 g of SBT/CPZ were not significantly prolonged in patients with moderate liver or kidney dysfunctions. 3. Clinical efficacy rates of SBT/CPZ in 217 patients were 93.1% (81/87) for pneumonia, 93.3% (14/15) for lung abscess, 78.9% (15/19) for acute exacerbation of chronic bronchitis, 57.1% (4/7) for diffuse panbronchiolitis, 72.4% (21/29), 74.4% (32/43) and 100% (9/9) for infections concurrent to bronchiectasis, chronic respiratory disease and pulmonary emphysema, respectively. Those were 50% (1/2) for bronchitis associated with lung cancer and 66.7% (4/6) for empyema. The overall efficacy rate was 83.4% (181/217). 4. Clinical efficacy rate of SBT/CPZ for pneumonia in patients with underlying diseases such as lung cancer, pulmonary tuberculosis and pneumoconiosis, etc, was 85.3% (29/34) and was not significantly different from the efficacy rate of 98.1% (52/53) in patients without these underlying diseases. 5. Of 30 patients who failed to respond of previous antibiotic treatments, 21 were effectively treated by SBT/CPZ. 6. Bacteriological eradication rates against Pseudomonas aeruginosa, Haemophilus influenzae and Streptococcus pneumoniae were 42.9% (9/21), 87.5% (14/16) and 100% (5/5), respectively. The overall eradication rate in all cases including polymicrobial infections was 72.8% (67/92). 7. The high levels of peak serum concentration of CPZ, and the difference between serum levels of SBT and of CPZ seemed to contribute to the high clinical efficacy. 8. Adverse reactions occurred in 2.8% (6/217) of the patients, and consisted primarily of rash and diarrhea. Laboratory abnormalities were observed in 8 patients during the study. These were elevations of S-GOT and S-GPT, and eosinophilia. 9. SBT/CPZ is a very useful drug in the treatment of lower respiratory tract infections as it has become available just in time when increase in resistant organisms to beta-lactams is notable.
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PMID:[Clinical evaluation of sulbactam/cefoperazone in lower respiratory tract infections]. 219 54

In Zimbabwe patients with pulmonary tuberculosis who are acid-fast bacilli (AFB) negative in the sputum are treated in the two month intensive phase with isoniazid, thiacetazone pyrazinamide and streptomycin (regimen A). Sputum positive patients receive regimen A plus rifampicin (regimen B). Both groups continue treatment with isoniazid and thiacetazone. 21 patients on regimen A and 19 on regimen B had clinical assessment and liver function tests performed at weeks 0, 2, 4, 8, and 12 weeks of treatment (during and four weeks after, the intensive phase of 8 weeks). Acetylator status was also assessed, no significant difference was found between patients on regimen A or B (41 per cent and 45 per cent fast acetylators respectively). Liver function tests results (alanine aminotransferase and alkaline phosphatase) showed a persisting rise during the intensive phase on both regimens, and further rise after four weeks in the continuation phase, this further rise reaching statistical significance in regimen B. These results are unexpected when compared to other studies but the regimens under investigation are not used elsewhere. The significant rise after stopping intensive therapy in regimen B suggests some protective effect of rifampicin against the hepatotoxicity of the regimen, possibly the isoniazid/thiacetazone component. Acetylator status did not influence the degree of hepatotoxicity.
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PMID:Effects of two pulmonary tuberculosis drug treatments and acetylator status on liver function in a Zimbabwean population. 222 25

We evaluated the therapeutic efficacy of ceftibuten (CETB, 7432-S), a new cephem antibiotic for oral use, in chronic respiratory tract infections. A daily dose of 400 mg (b.i.d.: 15 cases) or 600 mg (t.i.d.: 5 cases) of CETB was given orally for 3-14 days (mean: 10.6 days) to 20 patients: 9 with infected bronchiectasis, 3 with infection supervened on pulmonary emphysema, 3 with acute pneumonia (supervened on bronchiectasis in 2 of 3 cases), 2 with infected bronchial asthma, 1 each with infection supervened on old pulmonary tuberculosis, chronic bronchitis and pulmonary fibrosis. The clinical effects were excellent in 3, good in 11, fair in 3 and poor in 3. Eighteen strains were identified as causative organisms. Eight of 15 strains for which bacteriological responses were evaluable were eradicated by the use of CETB. Eosinophilia in 2 patients and an elevation of S-GPT value was observed in 1 patient. These adverse reactions disappeared after the completion of the therapy. From the above results, we conclude that CETB is one of the most useful antibiotics for oral use as a first choice in chronic respiratory tract infections.
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PMID:[Therapeutic efficacy of ceftibuten in chronic respiratory tract infections]. 239 48

Clinical evaluation and kinetics in serum of cefoperazone (CPZ) in patients with lower respiratory tract infections have been conducted as a multicenter trial participated by 20 institutions in Kyushu area during a period of 8 months from October 1984 to May 1985. Mean serum CPZ levels up to 4 hours following the end of intravenous infusion of either 1 or 2 g CPZ remained higher than the MIC80 of CPZ against major causative organisms of lower respiratory tract infections such as H. influenzae, P. aeruginosa, K. pneumoniae, and S. pneumoniae. Serum half-lives of CPZ following intravenous infusion were prolonged in the elderly and in patients who showed moderate liver or kidney dysfunction, but did not exceed twofold of normal value. Clinical efficacy rates of CPZ were 82.9% (34/41) against pneumonia, 80% (4/5) against lung abscess, 88.9% (32/36) against acute exacerbation of chronic bronchitis, 66.7% (2/3) against panbronchiolitis, 100% (1/1) against acute bronchitis, and 85.7% (12/14), 64.3% (9/14) and 70.0% (7/10) against infections concurrent to chronic respiratory diseases, pulmonary emphysema and bronchiectasis, respectively. The overall efficacy rate was 81.5% (101/124). Bacteriological eradication rates against P. aeruginosa, H. influenzae and S. pneumoniae were 60% (6/10), 88.9% (8/9) and 100% (3/3), respectively. The overall eradication rate including polymicrobial infection was 67.5% (27/40). The clinical efficacy rate of CPZ in patients with underlying diseases such as lung cancer, pulmonary tuberculosis, and pneumoconiosis, etc. was not significantly different from the efficacy rate in patients without these underlying diseases. Of 20 patients who failed to respond to previous antibiotic treatments, 13 were effectively treated by CPZ. Adverse reactions occurred in 6.7% (11/164) of the patients, and consisted primarily of rash, fever, diarrhea and loose stool. Laboratory abnormalities were seen in 5 patients during the study. These included elevations of S-GOT and S-GPT, eosinophilia and neutropenia. CPZ is a very useful drug in the treatment of lower respiratory tract infections because of its excellent clinical efficacy and rare incidence of abnormal accumulations in sera following the recommended 2-4 g/day administration even in the elderly.
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PMID:[Clinical evaluation of cefoperazone in lower respiratory tract infections]. 354 33

From January 1991 to December 1992, 419 patients with pulmonary tuberculosis were initially treated at Fukujuji Hospital. Among them, 190 patients, who were younger than 80 years old and had pulmonary tuberculosis with cavities or infiltration of extension 2 or 3, and/or were sputum-smear positive, had been treated by 6-month short course regimen containing pyrazinamide, 2HRS(E)Z/4HRE. And were eligible for the evaluation of the clinical usefulness of pyrazinamide-containing regimen for the initial treatment of pulmonary tuberculosis. The dose of pyrazinamide was 1.2 g per day irrespective of body weight. The patients of this treatment group consisted of 151 males and 39 females, and mean age of the males was 45.3 and that of the females was 43.8 years old. At the start of the treatment, 74% of the cases were smear positive, 70% were cavitary, and 6 cases each showed primary resistance to isoniazid and to streptomycin, respectively, and only one case showed resistance to both of isoniazid and streptomycin. There was no primary resistant case to either rifampicin or ethambutol. Bacteriologic negative conversion rates were 95% and 90% after 2 months of treatment by PZA-containing regimen and by the standard regimen, respectively, and treatment durations required to achieve the negative conversion of all cases were 3 and 6 months for respective regimens. Of 90 patients who completed 6-month PZA-containing regimen and could be followed-up, only one bacteriologic relapse (1.1%) was noticed. Elevation of serum GPT level higher than 150 IU/ml during the treatment was noticed in 6.3% of 175 cases under PZA-containing regimen in comparison with 4.0% of 174 cases under the standard regimen (not significant). The interval between the onset of the treatment and the detection of abnormal liver function was much shorter (mean 31.3 days) in the PZA-containing regimen than in the standard regimens (mean 63.4 days). Hyperuricaemia (> 10 mg/ml) was noticed in 46.7% of 57 males and 59.4% of 19 females tested, but pyrazinamide was not discontinued in any case due to arthralgia. These results clearly show that pyrazinamide can be used rather safely for Japanese tuberculosis patients. If the pyrazinamide-containing regimen [2HRS(E)Z/4HRE] is adopted as the new standard regimen in place of on-going standard regimen in Japan, 6HRS(E)/3HR, the duration of chemotherapy could be shortened by three months with the same level of both efficacy and safety. We recommended pyrazinamide-containing 6-month regimen, 2HRS(E)Z/4HRE, as the new standard regimen for the initial treatment of pulmonary tuberculosis.
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PMID:[Six-month short course chemotherapy containing pyrazinamide for initial treatment of pulmonary tuberculosis]. 783 20

In order to evaluate the incidence, predisposing factors and clinical course of antituberculous drug-induced liver injury in hepatitis B surface antigen (HBsAg)-positive carriers and non-carriers, in an area endemic for hepatitis B, we prospectively followed 240 patients (154 male, 86 female; mean age 40 years) who had received daily isoniazid, rifampicin, ethambutol and pyrazinamide for the treatment of pulmonary tuberculosis. Patients with heavy alcohol consumption, with pretreatment serum alanine aminotransferase (ALT) elevation and who had less than 3 months post-treatment follow-up were excluded from the study. Thirty-one (13%) patients were positive for serum HBsAg before treatment. Sixty-three (26%; 95% CI: 21-32%) patients developed antituberculous drug-induced liver injury. The incidence of drug-induced liver injury was significantly more frequent in patients > 35 years of age than in patients < or = 35 years of age (33 vs 17%; P < 0.05), but was not different between HBsAg carriers and non-carriers (29 vs 26%; P > 0.05). Using step-wise logistic regression analysis, patient age > 35 years was the only independent variable for predicting antituberculous drug-induced liver injury, while sex, acetylator phenotype, HBsAg carrier status and severity of tuberculosis were not. The peak serum ALT levels in antituberculous drug-induced liver injury were not significantly different between HBsAg carriers and non-carriers. Only one 61-year-old HBsAg carrier developed severe jaundice after 6 months antituberculous therapy; he subsequently died of hepatic failure. In conclusion, the incidence of antituberculous drug-induced liver injury was significantly higher in patients > 35 years of age than in patients < or = 35 years of age, but was not different between HBsAg carriers and non-carriers. Mortality occurred in an aged HBsAg carrier superimposed with antituberculous drug-induced liver injury.
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PMID:A prospective clinical study of isoniazid-rifampicin-pyrazinamide-induced liver injury in an area endemic for hepatitis B. 907 31


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