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)

Haemorrhagic fever with renal syndrome (HFRS) is an acute disease caused by Hantavirus and clinically characterised by abrupt onset of fever, various haemorrhagic manifestations and transient renal and hepatic dysfunction. We retrospectively reviewed 63 cases of HFRS in children from 13 different hospitals in Korea who presented over a 15-year period. The age of the patients ranged from 7 to 15 years, with a male to female ratio of 8 to 1. Fifty-four (86%) patients were 10 years or older. On admission, 24 (38%) were in the febrile phase and 35 (56%) were in the oliguric phase. Fever (100%) abdominal pain (91%), headache (76%) and vomiting (73%) were the most common symptoms. Backache, subconjunctival haemorrhage and hypertension were also noted in about one-third of patients. Hypotension was documented in only 7 (11%) patients. Leucocytosis (> 10,000/mm3) and thrombocytopenia (< 150,000/mm3) were noted in more than two-thirds of patients. Elevated blood urea nitrogen and serum creatinine was observed in 94% by the 7th (median) day of illness. Elevated aspartate aminotransferase and/or alanine aminotransferase were found in more than two-thirds of patients. Renal biopsy was performed in 12 patients and revealed various stages of acute tubular necrosis with occasional interstitial cell infiltration and oedema. Only 2 showed evidence of interstitial haemorrhage. Eleven patients required 1-3 days of dialysis and the remaining patients required only conservative management. Three (5%) patients died of shock, respiratory failure and pulmonary haemorrhage. All other patients recovered without sequelae. Although childhood cases were much less common than adults, clinical and laboratory findings were in general similar between children and adults.
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PMID:Haemorrhagic fever with renal syndrome in Korean children. Korean Society of Pediatric Nephrology. 781 97

Toenail tinea is a very recalcitrant dermatosis. Griseofulvin at > or = 500 mg/day is the current medication of choice, but it is minimally successful. In a controlled open trial ultramicrosize griseofulvin (UMSG) at doses of 660 and 990 mg/day was compared with itraconazole at 100 mg/day in 109 patients. At 4-week intervals, the patients were evaluated for their clinical and mycological statuses and adverse reactions. Treatment was given for up to 18 months. Compliance was checked by tablet counting. Response (cure, partial cure, marked improvement) was analyzed by the intent-to-treat method. Cured and partially cured patients were followed up. Except for one early dropout, the toenails (mean, 6 to 7) were involved. Cure or partial cure was found in 6% (UMSG at 660 mg), 14% (UMSG at 990 mg), and 19% (itraconazole at 100 mg) of patients (P = 0.2097); marked improvement was found in 36, 44, and 39% of patients in the three treatment groups, respectively. Most patients had to be treated for 18 months. Failure was related to short medication periods (adverse drug reactions, dropout). While stable cure was not obtained with UMSG at 660 mg, the higher dose of UMSG and itraconazole gave stable cures in the other patients. Side effects of nausea, diarrhea, and headache were found in 20, 26, and 11 patients, respectively (P = 0.0028), and the numbers in whom medication had to be discontinued differed, too (P = 0.0137). While there was no major difference with glutamic-pyruvic transaminase and gamma-GT, total and low-density lipoprotein cholesterol levels declined slightly in the itraconazole group (P = 0.0357 and P = 0.0639, respectively, at 3 months). More than 70% of the patients had an average compliance of > or = 90%; four patients (two dropouts) were poor compliers. In conclusion, it appears questionable whether griseofulvin can continue to be considered the "gold standard" in the treatment of toenail tinea. At present, itraconazole at 100 mg shows better efficacy and is better tolerated.
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PMID:Treatment of tinea unguium with medium and high doses of ultramicrosize griseofulvin compared with that with itraconazole. 825 24

An epidemic of Q fever in Berlin affected at least 80 patients (45 females, 35 males; age range 1-75 years). Sheep were identified as the focus of infection: they had been brought to a veterinary clinic because of nonspecific symptoms. The peak incidence of the infection was in April and May, 1992. Most of the patients were staff or students at the veterinary clinic. This is the most northern and, at the same time largest, Q fever epidemic recorded in Germany over the last 28 years. The complement fixation reaction (CFR) was not helpful diagnostically in the acute stage of the disease as it remained negative in the first 14 days (CFR < or = 1:5). Most of the patients had sudden fever to over 40 degrees C, severe headache and dry cough. Pulmonary infiltrates were seen in the chest radiograph of 8 of the 10 patients presented in this contribution. Auscultation was largely negative. Two patients had signs of hepatic involvement (GPT as high as 71 U/l). The drug of choice was doxycycline at a dosage of 200 mg twice daily for 14 days.
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PMID:[A Q fever epidemic in Berlin. The epidemiological and clinical aspects]. 850 Apr 12

This 4-week, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, multicenter study was designed to compare the efficacy and safety of etodolac and nabumetone in the treatment of patients with active osteoarthritis (OA) of the knee. Ninety-one patients received etodolac 400 mg twice daily, 89 received nabumetone 1500 mg once daily, and 90 received placebo. Both active treatments significantly improved the patients' condition relative to baseline (P < or = 0.001) at all evaluations during treatment and relative to placebo (P < or = 0.05) by visit 4. Improvement relative to placebo in investigator's global assessments was earlier in the etodolac group (ie, by visit 3) than in the nabumetone group. At visit 4, improvement in investigator's and patient's global assessment scores, and in the distribution of investigator's assessment scores, was significantly (P < or = 0.05) greater in the etodolac group than in the nabumetone group. Other than hypokalemia, which occurred only in three patients in the nabumetone group (P = 0.035), there were no significant differences among the groups in the frequency of study events or premature discontinuation from the study as a result of study events. Study events considered at least possibly treatment related were reported for 26 patients in the etodolac group (28.6%), 20 in the nabumetone group (22.5%), and 23 in the placebo group (25.6%). The most frequently reported symptoms for all groups were dyspepsia, nausea, and headache. Four patients treated with nabumetone (4.5%) had elevations in aspartate aminotransferase or alanine aminotransferase during treatment. The results of this study show that etodolac 400 mg twice daily is at least as effective as nabumetone 1500 mg once daily and is equally well tolerated in the treatment of patients with active OA of the knee; etodolac may have an earlier onset of action and/or a relatively greater efficacy in patient and investigator global assessments than nabumetone.
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PMID:Double-blind, placebo-controlled comparison of the safety and efficacy of orally administered etodolac and nabumetone in patients with active osteoarthritis of the knee. 856 24

Interferon-alpha is currently the only available treatment for HCV hepatitis. We assessed the safety and efficacy of 6 month course of interferon therapy in 18 consecutive liver transplant recipients with recurrent HCV hepatitis and report the long-term response with maintenance interferon. Median follow-up after the institution of interferon was 24 months. Complete response was defined as normalization of both aspartate and alanine aminotransferase. Complete response after 6 months of interferon was observed in 28% (5/18); an additional 33% (6/18) of the patients were late responders. Overall, 61% (11/18) of the patients had long-term sustained normal response at a median follow-up of 24 months. Long-term sustained response was observed in 73% (8/11) of the patients who continued interferon beyond 6 months vs. 43% (3/7) in those who received 6 months of interferon. Fatigue, headache and cytopenia were the most commonly observed side-effects occurring in 39%, 22% and 28% of the patients, respectively. Discontinuation of interferon, however, was not required in any of the patients. Rejection was documented in 6% (1/18) patients receiving interferon; this incidence was not higher than rejection episodes occurring > 6 months post-transplant in other recipients transplanted during the same period and who did not receive interferon. Responders had a trend towards later recurrence of HCV hepatitis after transplantation. In conclusion; maintenance interferon was well tolerated and appeared to improve the long-term outcome in our patients; however, future studies should evaluate this in a controlled trial.
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PMID:Interferon-alpha therapy for hepatitis C virus recurrence after liver transplantation: long-term response with maintenance therapy. 888 7

Therapy with ribavirin for 6-12 months is associated with decreases in serum aminotransferases in some patients with chronic hepatitis C. We have assessed the practicality and safety of prolonged therapy with ribavirin. Six patients with chronic hepatitis C were given 1000-1200 mg of ribavirin daily for 24 months. Serum aminotransferases and hepatitis C virus (HCV) RNA levels were monitored during and after therapy. Liver biopsies were carried out before and at the end of treatment. With therapy, mean serum alanine aminotransferase (ALT) levels fell from 161 U/L to 45 U/L at 12 months and to 39 U/L at 24 months. HCV RNA levels did not change. Liver histology improved in five and was unchanged in one patient. When therapy was stopped, aminotransferases rose to pretreatment levels. Side effects included mild fatigue and headaches. Two patients developed gallstones during therapy, perhaps caused by the chronic haemolysis that occurred in all patients. In conclusion, prolonged therapy with ribavirin can result in sustained improvements in serum aminotransferases and hepatic histology in a proportion of patients with chronic hepatitis C. Ribavirin therapy does not cause decreases in viraemia and, therefore, probably must be continued indefinitely to provide lasting benefit. The advantages of such therapy must be weighed against possible long-term side-effects.
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PMID:Prolonged therapy of chronic hepatitis C with ribavirin. 891 4

The clinical trial development programme of mirtazapine (Org 3770), performed in Europe and the United States, demonstrated an outstanding safety profile of this compound. The evaluation of the safety was based on data from all patients who took at least one dose of study medication during studies comparing mirtazapine with placebo, amitriptyline or other active comparators. A general indication of mirtazapine's safety is the significantly lower percentage of patients (65%) who complained of any adverse clinical experiences compared with the placebo- (76%) or amitriptyline-treated group (87%). Moreover, drop-out rates due to adverse clinical experiences were significantly lower than in the amitriptyline-treatment group. Mirtazapine has virtually no anticholinergic, adrenergic or typical selective serotonin reuptake inhibitor (SSRI) side effects. The only significantly higher incidences versus placebo were seen in the adverse clinical effects of drowsiness (23% versus 14%), excessive sedation (19% versus 5%), dry mouth (25% versus 16%), increased appetite (11% versus 2%) and weight increase (10% versus 1%). These complaints were typically mild and transient in nature, and decreased over time despite increased doses of mirtazapine. In contrast, significantly higher incidences of headache (5% versus 10%) and weight decrease (2% versus 6%), symptoms commonly seen in depressed patients, were recorded in the placebo-treated patients. Also, typical SSRI adverse events, such as nausea, vomiting, diarrhoea and insomnia, and symptoms of sexual dysfunction were registered less frequently in mirtazapine-treated patients than in the placebo-treated patients. Approximately 10% of the mirtazapine-treated patients in the clinical trial programme were older than 65 years. The pattern of adverse clinical experiences seen in this group of patients is fully in line with that seen in the overall patient population. The analysis of vital sign indices, i.e. blood pressure and heart rate, showed that no changes occurred with mirtazapine treatment; this pattern was fully comparable to that seen with placebo. Furthermore, very low incidences of clinically relevant changes in laboratory indices, such as the liver enzymes alanine aminotransferase and aspartate aminotransferase or neutropenia, were recorded in each treatment group. Mirtazapine has a very low seizure-inducing potential: only one case was recorded in a patient with a history of seizures during previous treatment with clomipramine. The low seizure-inducing potential combined with a lack of cardiotoxic properties allows safety in an overdose of mirtazapine, even in elderly patients. The only symptom seen in the patients taking an overdose of mirtazapine alone or in combination with other drugs was excessive but transient somnolence, which resolved spontaneously within a few hours. In conclusion, the new antidepressant mirtazapine offers clinicians a unique combination of strong efficacy and good safety.
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PMID:Safety of mirtazapine: a review. 893 8

Bropirimine (U-54461S), an oral interferon (IFN) inducer that has also a direct antiproliferative activity, is a novel antitumor agent. To investigate the safety and pharmacokinetics of bropirimine tablets and to measure IFN concentrations in patients with cancer, Phase I studies were conducted. In single dose study (0.25 to 3g) and multiple-dose study with one-day dosing (1 or 2g, every one or two hours, three times a day), bropirimine treatment was well tolerated by the patients with cancer. In multiple-dose study with consecutive days dosing (1 or 2g, every 2 hours, three times a day for 3 or 5 consecutive days), a regimen with a dose of 1g orally administered every two hours, three times a day for three consecutive days was considered to be tolerable to cancer patients. Adverse drug reactions frequently observed were generalized malaise, fever, nausea/vomiting, anorexia, headache/dull headache, and tachycardia. Abnormalities in laboratory tests frequently observed were leukemia, neutropenia, thrombocytopenia, and elevation in GOT/GPT. IFN was not induced in any patients in the single dose study. It was, however, induced in 3 of 16 cases (18.8%) in the one-day dosing study and in 6 of 7 cases (85.7%) in the consecutive days dosing study. As to clinical antitumor efficacy, a decrease in size of the tumor lesions and improvement in subjective/objective symptoms were noted in two cases in the one-day dosing study. With these findings, the regimen with the dose of 1g orally administered every two hours, three times a day for three consecutive days with a four-day drug-free interval per week was recommended for early phase II studies.
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PMID:[Bropirimine (U-54461S) phase I clinical studies]. 897 2

The inhibitory effects of GG032X tablets, a new dosage form (fast dispersing tablet) of ondansetron, 5-HT2 receptor antagonist, on nausea and emesis induced by cisplatin (CDDP), were investigated along with safety and usefulness. Subjects were chemotherapy patients starting CDDP administration for the first time, who were receiving a high single dose of CDDP (50 mg/m2 or more and intravenous drip infusion of less than 4 hours), or lower multiple doses of CDDP (a single dose of 10 mg/m2 or more, administered intravenously for 3-5 consecutive days). GG032X tablets were administered orally 1-2 hours before CDDP administration. In lower multiple doses of CDDP, GG032X tablets and CDDP were administered, as much as possible, at the same respective time when they were administered on the first day. Efficacy of GG032X tablets was evaluated in terms of inhibitory effect on nausea and emesis 24 hours after administration of a high single dose of CDDP, and of the inhibitory effect on nausea and emesis during the study period (3-5 days) in lower multiple doses of CDDP. Efficacy, safety and usefulness were evaluated in accordance with the evaluation criteria used in the clinical study of already-approved ondanstron tablets. In a high single dose of CDDP, the cases judged "effective" or better in the investigation of the inhibitory effect of the drug on nausea and emesis, accounted for 52.9% (63/119 cases). As for the overall safety rating, the cases judged as "safe" accounted for 87.0% (107/123 cases), and as a "minor safety problem" accounted for 13.0% (16/123 cases). As for the usefulness rating, the cases judged "useful" or better accounted for 52.1% (62/119 cases). Major adverse effects included headache, fever, atrial fibrillation and increases in total bilirubin, GOT and GPT values. None of these was serious, and the patients recovered without any treatment or by nosotropic therapy. Meanwhile, in lower multiple doses of CDDP, the inhibitory effect judged "effective" or better accounted for 70.6% (12/17 cases). As for the overall safety rating, all cases were judged "safe". In terms of usefulness, those cases judged "useful" or better accounted for 70.6% (12/17 cases). No adverse effect was observed. Study results of these two groups were almost the same as those for already-approved ondansetron tablets. According to the results of questionnaires for the patients who participated in the study and took GG032X tablets, the drug was found to be easy to take and had favorable results. Based on the above results, GG032X tablets were evaluated as having the same inhibitory effect as the already-approved ondansetron tablets against CDDP-induced nausea and emesis, and were considered safe and clinically useful.
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PMID:[Clinical efficacy of GG032X tablets, a new dosage form of ondansetron (fast dispersing tablet), on cisplatin-induced nausea and emesis]. 921 10

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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