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)

In order to clarify the toxicity of the antineoplastic drugs, bleomycin (BLM), peplomycin (PEP) and cis-diamminedichloroplatinum (CDDP), which are commonly used to treat head and neck cancer by simultaneous administration, the semiacute toxicity of each of these drugs in rats was studied as an initial step. Body-weight change, general behavior, red blood cell count (RBC), white blood cell count (WBC), serum biochemistry (s-GOT, s-GPT, BUN, GLU, ALB, TP), A/G ratio, relative organ weight and histopathological features were determined. BLM and PEP given by ip administration once a week produced severe diarrhea, decreased diet consumption, emaciation, piloerection and loss of hair, enhancements of RBC and WBC, several changes in serum biochemistry, proliferation and mitosis of epithelial cells in the forestomach and occasional granular and vacuolar degeneration in the liver. CDDP administered in the same manner produced a significant decrease of WBC, several changes in serum biochemistry parameters especially BUN, an increased focal-segmental mesangial matrix in the glomeruli and vacuolar degeneration of epithelial cells of the convoluted tubule of the kidney.
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PMID:A study on the toxicity of antineoplastic drugs (bleomycin, peplomycin and cis-diamminedichloroplatinum) by simultaneous administration (Part 1). 248 79

Fluconazole, a novel triazole antifungal agent, was given orally or intravenously to 10 patients with pulmonary mycosis (7 patients with primary pulmonary cryptococcosis and 3 with pulmonary aspergillosis). Routes of administration were changed in some patients depending on their condition. Two patients from whom foci was removed by surgical operations were excluded from the efficacy assessment. Clinical efficacies in the remaining 8 patients were good in 2 cases and fair in 3 cases of pulmonary cryptococcosis; excellent in 1 case of pneumonia due to Aspergillus; and fair in 1 case and poor in the other case of pulmonary aspergilloma. Side reactions developed in 9 patients who received intravenous drip infusion were nausea or loss of appetite in 3 patients, fever and/or feverish sensation in 3, vascular pain in 1 and diarrhea and eruption in 1. In the patient who reported fever the drug was discontinued and in the patient who complained of pain at the site of injection, dosing was changed to the oral route but was discontinued due to elevated GOT, GPT, Al-P and gamma-GTP. Seven patients who received the drug orally did not report side effects except 2 patients. None of these side effects reported was serious and from the above results, fluconazole was considered to be a useful agent for the treatment of pulmonary mycosis.
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PMID:[Clinical efficacy of fluconazole in the patient with pulmonary mycosis]. 254 Mar 59

1. Cefmenoxime (CMX) was administered with a dosage regimen of 20-25 mg/kg, 2-3 times daily (40-75 mg/kg/day) by intravenous drip over 30 minutes to 9 neonates with bacterial infections including purulent meningitis and septicemia. Clinical responses to the treatment were excellent in 7 and poor in 2. Bacteriological responses were "eradication of pathogens" from 8 of them except another patient with an infection due to Staphylococcus aureus. 2. Adverse reactions to CMX were observed in 6 of 18 neonates treated with the drug: diarrhea, oral thrush, and the elevation of S-GOT, S-GPT, LDH and alkaline phosphatase. None of the reactions, however, necessitated the discontinuation of the treatment. 3. Changes in blood concentrations of CMX in neonates with ages between 0 and 30 days were followed. These subjects included 16 mature neonates and 10 neonates with low birth weights. Intravenous drip infusion of 20 mg/kg of CMX over 30 minutes was immediately followed by peak blood CMX concentrations of 34.6-72.7 mcg/ml (mean +/- S.D.: 50.4 +/- 11.3 mcg/ml) in the mature neonates, and 22.3-78.2 mcg/ml (55.5 +/- 16.5 mcg/ml) in the neonates with low birth weight. Blood half-lives of the drug in the mature neonates were in the range from 1.7 to 20.7 hours (5.9 +/- 6.6 hours) in subjects with ages of 0-3 days, and 1.1-3.5 hours (2.0 +/- 0.8 hours) in subjects of 4-25 days. In neonates with low birth weight, they were 3.4-10.2 hours (7.2 +/- 2.7 hours) in subjects of 0-2 days, and 1.4-5.5 hours (3.0 +/- 1.5 hours) in subjects of 4-30 days. In other words, the blood half-lives of the drug tended to be longer in younger subjects. 4. Concentration of CMX in cerebrospinal fluid (CSF) were determined in a patient in acute stage with purulent meningitis caused by Mycoplasma hominis. Intravenous drip infusion of 80 mg/kg of CMX over 30 minutes was followed by CSF concentrations of 7.7-15.5 mcg/ml. 5. MICs of CMX for clinical isolates were determined. The drug was proved to have excellent antibacterial activities against Escherichia coli (3 strains) and group B hemolytic streptococci (2 strains) and these MICs were comparable to those of cefotaxime. The MIC of CMX for S. aureus (1 strain) was high at 25 mcg/ml with an inoculum size of 10(8) CFU/ml. This MIC value of CMX was higher than that of cefmetazole.
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PMID:[A preclinical and clinical study of cefmenoxime in newborns]. 261 17

During 8 months from October 1986 to May 1987, the clinical efficacy of sulbactam/ampicillin (SBT/ABPC) was evaluated in 63 pediatric inpatients with various infections. Clinical efficacies were evaluable in 58 patients among them (consisting of 2 patients with sepsis, 3 with tonsillitis, 12 with bronchitis, 6 with bronchopneumonia, 24 with pneumonia, 1 with phlegmon, 2 with lymphadenitis, 1 with impetigo and 7 with urinary tract infection) and were excellent in 40 patients and good in 17 with an overall efficacy rate of 98.3%. Bacteriological efficacies were assessed in 25 patients and 27 strains of organisms (consisting of 3 strains of Staphylococcus aureus, 2 Streptococcus pneumoniae, 1 Streptococcus pyogenes, 2 beta-Streptococcus, 1 Gram-positive cocci, 5 Escherichia coli, 1 Enterobacter aerogenes, 7 Haemophilus influenzae, 2 Haemophilus parainfluenzae, 1 Branhamella catarrhalis, 1 Proteus mirabilis and 1 Salmonella subgenus I). Bacteriological eradication rates were 88.9% for Gram-positive organisms, 66.7% for Gram-negative organisms and 74.1% overall. No superinfection was observed in any of patients treated. Side effects and clinical laboratory parameter abnormalities observed consisted of diarrhea in 7 (11.1%) of the 63 patients, eosinophilia in 2 (3.3%) of 61 tested, thrombocytosis in 3 (5.5%) of 55, elevation of direct bilirubin in 1 (3.3%) of 30, elevation of total bilirubin in 1 (3.1%) of 32, elevation of GOT in 4 (6.8%) of 59 and elevation of GPT in 1 (1.7%) of 59 patients tested. As an effect on the hemostatic mechanism of this drug, PIVKA II was detected in 1 patient (4.2%) of 24 tested, but findings of other coagulation tests were normal and none of patients showed bleeding tendency or inhibition of platelet aggregation. From the above results, it appears that SBT/ABPC is an efficacious and safe drug in the treatment of bacterial infections of pediatric patients.
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PMID:[Clinical studies on sulbactam/ampicillin in the field of pediatrics]. 266 49

Pharmacokinetic and clinical studies on sulbactam/ampicillin (SBT/ABPC) were carried out in the field of pediatrics. 1. Absorption and excretion Serum levels and urinary excretion of SBT/ABPC were studied in 4 children with ages 6 to 8 years. The mean serum concentration of SBT at 15 minutes following a single intravenous injection of 30 mg/kg of SBT/ABPC was 27.4 +/- 2.2 micrograms/ml and that of ABPC was 42.8 +/- 3.9 micrograms/ml, and their concentrations declined with mean half-lives of 1.06 +/- 0.15 hours and 0.84 +/- 0.05 hour, respectively, and at 6 hours were 0.3 +/- 0.2 microgram/ml and 0.2 +/- 0.1 microgram/ml on the average, respectively. The urinary recovery rates of SBT and ABPC at 6 hours after the injection were 59.0 +/- 22.4% and 58.4 +/- 25.3% on the average, respectively. 2. Clinical study SBT/ABPC was used for the treatment of a total of 36 pediatric patients with ages ranging 2 months to 11 years and it's clinical effectiveness, bacteriological efficacy and adverse effects were evaluated. Clinical efficacies in 5 patients with acute purulent tonsillitis, 26 with acute pneumonia and 1 with acute pyelonephritis were judged to be excellent in 27 cases and good in 5 cases with an overall efficacy ratio of 100.0%. Clinical efficacies in 6 patients whose infections were caused by beta-lactamase producing strains were judged to be excellent in all cases. Bacteriological efficacies of SBT/ABPC were assessed on 1 strain of Staphylococcus aureus (beta-lactamase producing strain), 2 strains of Streptococcus pneumoniae, 16 strains of Haemophilus influenzae (5 beta-lactamase producing strains and 11 non-beta-lactamase producing strains), 1 non-beta-lactamase strain of Haemophilus parainfluenzae and 2 strains of Escherichia coli (non-beta-lactamase producing strains). All strains except 1 strain of H. influenzae (beta-lactamase producing strain) which decreased in number were eradicated with a bacteriological eradication rate of 95.5%. Only 1 patient complained of diarrhea which was suspected to be related to the drug. No other side effect was reported. Elevations of GOT and GPT were observed in only 1 patient. The above results suggested that SBT/ABPC was a useful drug with preferable safety profile in the treatment for pediatric patients with infectious disease caused by beta-lactamase producing strains as well as those by non-beta-lactamase producing strains.
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PMID:[Studies on sulbactam/ampicillin in the field of pediatrics]. 266 50

Pharmacokinetics and clinical studies of imipenem/cilastatin sodium (IPM/CS), a combined preparation of a new carbapenem antibiotic and a dehydropeptidase-I inhibitor, respectively, were carried out in neonates and premature infants in a joint study by a co-research group. 1. Peak blood levels of IPM/CS when administered at 10 mg/10 mg/kg or 20 mg/20 mg/kg by 30- or 60-minute intravenous drip infusion were achieved at the end of infusion. A dose response was clearly observed between the doses and the peak levels achieved. 2. The areas under the blood concentration time curve (AUC) of CS were greater than those of IPM in most patients. Blood half-lives of IPM and CS tended to be longer in younger neonates and premature infants than in older subjects. The blood half-life of CS tended to be longer than that of IPM. 3. Cumulative urinary recovery rates of CS were greater than those of IPM, cumulative urinary recovery rates tended to be greater in older neonates and premature infants than younger subjects. 4. One hundred and thirteen patients were treated for bacterial infections with IPM/CS and 32 patients were treated prophylactically. Daily doses of IPM/CS ranged from 9 mg/9 mg/kg to 150 mg/150 mg/kg. 5. Clinical efficacies of IPM/CS were evaluated in a total of 56 patients with identified etiologic pathogens. The efficacy rate was 98.2% with 33 patients rated as excellent, 22 patients as good and 1 patient as fairly good. (Diagnoses were sepsis in 10 patients and meningitis in 2 patients, etc.) Fifty-seven patients with no identified etiologic pathogens were rated as excellent for 22 patients, good for 34 patients and fairly good for 1. The efficacy rate in these patients was 98.2%. Thirty-two patients were treated prophylactically and the results obtained were satisfactory. 6. Bacteriologically, the eradication rate was 94.5% in 56 patients; i.e., 52 were eradicated, 2 were decreased, 1 persisted and 1 was unknown. 7. Adverse effects were observed in 7 (4.4%) of 160 patients, i.e., 2 patients had diarrhea and 2 patients had rash, etc. Abnormal laboratory data considered related to the therapy occurred in 28 (17.6%) of 159 patients, with 10 patients with eosinophilia (6.3%) and elevation of GOT and/or GPT, etc. All these were non serious, and all values returned to normal after discontinuance of therapy. An abnormal prothrombin (PIVKA II) was observed in 1 of 10 patients tested.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Pharmacokinetic and clinical evaluation of imipenem/cilastatin sodium in neonates and premature infants. A study of imipenem/cilastatin sodium by a perinatal co-research group]. 267 29

Data from 1,878 courses of intravenous ciprofloxacin therapy, administered to 1,869 patients in 59 clinical trials, were analyzed for drug safety. The 985 men and 884 women had a mean age of 50 years, and more than one third were over 60 years of age. An overwhelming majority had at least one accompanying systemic illness, and the condition of more than half the patients was only fair or poor at the onset of therapy. Ciprofloxacin was administered in a unit dose of either 200 mg (68 percent of the patients) or 300 mg (28 percent) by intravenous infusion, generally over 30 minutes every 12 hours, at a mean daily dosage of 456 mg. The duration of intravenous therapy ranged from one to 57 days, with a mean of seven days; over 1,000 patients were treated for more than five days. Adverse events considered probably or possibly related to intravenous ciprofloxacin were reported in 15.8 percent of the courses; therapy was discontinued prematurely in 3 percent. Local reactions at the site of infusion were the most common, occurring in 4.4 percent of the courses. Changes in blood chemistry values (4.1 percent) included increases in alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Reports of adverse effects referable to the gastrointestinal tract (3.0 percent) were primarily nausea and diarrhea. Central nervous system reactions (1.8 percent) included convulsive seizures, headache, and dizziness. In comparative trials, events considered probably or possibly drug related were reported for 17.3 and 13.6 percent of the ciprofloxacin- and ceftazidime-treated patients, respectively. The incidence of adverse events other than local reactions at the infusion site was not significantly different between the ciprofloxacin- and ceftazidime-treated patients (12.7 percent versus 11.0 percent, p greater than 0.2).
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PMID:Safety of intravenous ciprofloxacin. A review. 268 31

Imipenem-cilastatin was evaluated for tolerability and efficacy in a multicenter open, noncomparative trial involving 178 infants and children with bacterial infections. Imipenemcilastatin was administered in total daily dosages of 100 mg/kg for patients up to 3 years of age and 60 mg/kg for those more than 3 years of age. Favorable clinical response was achieved in 98 of 100 patients judged evaluable for efficacy. Adverse effects were generally mild and reversible and included diarrhea alone or with vomiting (5.1%), irritation of intravenous infusion site (3.3%) and rash (2.2%). Changes in laboratory test values reported most frequently were thrombocytosis (8.9%), elevations in aspartate aminotransferase (7.9%) and alanine aminotransferase (5.6%) and eosinophilia (8.4%). This safety profile appears to be comparable to that of other beta-lactam antibiotics. Moreover imipenem-cilastatin was effective in infections caused by a broad spectrum of pathogens that include Haemophilus influenzae, Staphylococcus aureus, P. aeruginosa and anaerobes. These attributes suggest that imipenem-cilastatin should be safe and effective in selected pediatric patients.
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PMID:Imipenem-cilastatin in pediatric patients: an overview of safety and efficacy in studies conducted in the United States. 268 88

For the purpose of evaluation of clinical efficacy, safety and usefulness on acute infectious enteritis (bacillary dysentery, and enteritis caused by Salmonella spp., Campylobacter spp., enteropathogenic E. coli, and so on), T-3262, a newly developed pyridone-carboxylic acid derivative, was administered to a total of 136 patients and carriers. In addition, in vitro antibacterial activity of T-3262 was determined against the clinical isolates, and compared with those of nalidixic acid (NA), pipemidic acid (PPA), enoxacin (ENX), norfloxacin (NFLX) and ofloxacin (OFLX). The daily dose of 450 mg of T-3262 was administered orally three times after meals for 5 days, with the exception of 7 day administration against Salmonella enteritis. A total of 89 cases were evaluated; 23 with Shigella spp., 30 with Salmonella spp., 15 with Campylobacter spp., 6 with enteropathogenic E. coli, and 15 cases with the other pathogens or pathogen-negative. The efficacy on clinical symptoms judging from duration of fever, and duration of diarrhea and abnormal stool character was 100% in all the enteritis except enteropathogenic E. coli enteritis, in which it was 50% (n = 2). Concerning bacteriological response, elimination of the causative organisms from the feces was 100% in Shigella spp. (n = 19), Salmonella spp. (n = 30), and enteropathogenic E. coli (n = 6), although 64.3% in Campylobacter spp. (n = 14). As an adverse effect, epigastric discomfort was observed in one (0.8%) of 130 cases. Deteriorations in laboratory findings were seen in five (6.2%) of 81 cases, consisting of two with elevated GOT and GPT, two with elevated GPT, and one with increased eosinophils count, although they were all slight in degree. MICs of T-3262 which inhibited 90% of the isolates of Shigella spp, Salmonella spp., and Campylobacter spp., were 0.025, 0.05, and 0.78 microgram/ml, respectively. These values were lowest among the quinolone derivatives tested, except that the MIC90 against Campylobacter spp. was the same as that of ofloxacin.
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PMID:[Clinical trial of T-3262 on acute enteritis. Japan Research Committee of T-3262, Research Group for Acute Infectious Enteritis]. 269 41

Intravenous administration of sulbactam/ampicillin (SBT/ABPC) was evaluated in pediatric patients. The serum half-lives of both ABPC and SBT were approximately 1 hour following the intravenous injection or intravenous drip infusion of 20-35 mg/kg, and 30-50% of ABPC and 30-70% of SBT were recovered in the urine 6 hours. Cerebrospinal fluid concentrations of ABPC and SBT were 0.76 and 0.68 micrograms/ml, respectively, at 1 hour after intravenous drip infusion of the 58 mg/kg, and concentration ratios of the drugs in cerebrospinal fluid/serum were 6.39 and 5.71%, respectively. Thirty-four pediatric patients were treated with intravenous drip infusion of SBT/ABPC in doses ranging from 54 to 150 mg/kg divided into 3 times a day. The rate of clinical efficacy was 93.5% and the bacterial elimination rate was 92.3%. The synergistic activity of sulbactam with ampicillin was demonstrated against beta-lactamase-producing Staphylococcus aureus and Haemophilus influenzae isolated from patients in the present study. The side effects of SBT/ABPC were observed in 6 patients (5 diarrheas; 1 diarrhea with vomiting) out of 34 patients administered. Eosinophilia (2 patients) and a slight elevation of GOT (1 patient), GPT and LDH (1 patient) were observed. The tolerance to the therapy, however, was good.
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PMID:[Clinical and pharmacokinetic studies on intravenous administration of sulbactam/ampicillin in pediatrics]. 274 46


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