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)

Clinical studies on cefamandole were carried out with the following results. (1) Cefamandole was administered 100 mg/kg/day (q.i.d.) by intravenous route to 29 cases of children. In 10 out of 29 cases bacteriological effect was observed. Bacteriological response was effective in 8 cases (80.0%). Clinical responses were effective in 27 cases (93.1%). (2) As to adverse reactions, granulocytopenia and elevation of S-GOT, S-GPT developed in each two cases.
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PMID:[Clinical studies of cefamandole in children (author's transl)]. 51 85

The phase II trial of natural interferon-alpha (HLBI) in treatment of adult T-cell leukemia was carried out as a cooperative study. Of the 24 cases which could be evaluated, 3 cases in crisis type and 5 cases in chronic type with lymphadenopathy and/or skin infiltration achieved PR, giving a response rate of 33.3%. The anti-tumor effect of HLBI for skin lesion could be assessed in 16 cases with skin infiltration, giving a response rate of 50.0% (5 CR and 3 PR) and demonstrating a high efficacy. Of the 31 eligible patients, side effects were recognised in 27 (87.1%). Major subjective and objective symptoms were fever (38.7%), fatigue (25.8%), anorexia (12.9%) and nausea (12.9%), and leukopenia (22.6%), granulocytopenia (38.7%), thrombocytopenia (38.7), elevation of GPT (12.9%) and GOT (12.9%) were observed.
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PMID:[Clinical study on the effect of natural alpha-interferon (HLBI) in the treatment of adult T-cell leukemia]. 305 2

A clinical Phase I study of recombinant human interferon alpha A (Ro 22-8181) was performed in patients with malignant tumors; twenty of them received an American product and seven others a domestic product. Both products were administered in single intramuscularly injected doses of 18, 36, 50, 75 and 100 X 10(6)U. Main side effects included fever and influenza-like symptoms (headache, chill/shivering, general fatigue, lumbago), and digestive symptoms (anorexia, nausea/vomiting). Numbness of fingers or limbs and somnolence were also observed in higher dose groups, but these symptoms all disappeared on the day of administration or by the 3rd day after administration. Abnormal laboratory findings included leukopenia, granulocytopenia, lymphocytopenia, thrombocytopenia and increased GOT/GPT/LDH, but these returned to normal by the 10th day after administration. The peak blood concentration was correlated with the dose, falling to the base line 72 hr after administration. The American product and the domestic product were nearly comparable in the type and incidence of their side effects, and also produced generally comparable blood concentrations. Furthermore, increased anti-IFN-alpha antibody titer was not observed in any of the patients; and the Prick Test proved negative in all of them. No significant changes were observed in any immunological parameters, either.
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PMID:[Phase I study of recombinant human interferon alpha A (Ro 22-8181) in patients with malignant tumors]. 400 81

6059-S was administered to 32 children with various acute bacterial infections (bronchopneumonia 11, bronchitis 1, pyelonephritis 5, acute enteritis 6, purulent infection 4, secondary infection due to agranulocytosis 5) at the dose of 21 to 190 mg/kg/day for 2 to 12 days. The clinical response of 6059-S was very satisfactory in all 17 cases with the injection of respiratory tract or urinary tract infection, but it was not so favourable in 5 cases of secondary infection due to agranulocytosis. The overall clinical response was excellent in 5, good in 20, fair in 4, and failure in 3 with effective rate of 78%. As to side effect, each one case diarrhea and elevation of GOT and GPT was noted.
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PMID:[Clinical studies on 6059-S in the field of pediatrics (author's transl)]. 645 63

Patients with bronchopulmonary infections were treated with cefoperazone (CPZ), and the serum and pleural effusion concentrations were determined after 2g CPZ drip infusion. The following results were obtained: Eight of 10 patients treated with CPZ responded with a significant clinical improvement. Side effects were found in 4 cases; eruption in 1 case, fever and granulocytopenia in 1 case, elevation of GPT in 1 case, and thrombocytopenia in 1 case. But these side effects disappeared immediately after cessation of CPZ treatment. Intravenous drip infusion of 2 g CPZ yielded a peak serum concentration of 112.0 --210.0 micrograms/ml immediately after the end of drip infusion, and a peak pleural effusion concentration of 8.8--43.0 micrograms/ml at 2--6 hours after the end of drip infusion. The ratio of peak pleural effusion concentration to peak serum concentration was 4.4--26.9%.
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PMID:[Clinical experience with cefoperazone in respiratory tract infections and studies on its penetration into pleural effusion]. 667 53

The purpose of this study was to investigate the toxicologic responses of mice to vincristine (VCR), an established antitumor drug, and to compare them with those reported for dogs, monkeys, and humans. This comparison was expected to facilitate the continuing appraisal of the mouse as a model for toxicologic responses to antitumor drugs in human patients. In duplicate experiments, male B6D2F1 mice were treated with 1.0, 1.5, 2.0, and 3.0 mg/kg of VCR in single IP doses. These sublethal doses corresponded to 0.25, 0.40, 0.50, and 0.80 LD50. On posttreatment days 1, 3, 6, 10, 14, and 21, groups of mice were killed and blood and other tissues were collected for hematologic (8 tests), clinical chemical (15 tests), and histopathologic (11 tissues) evaluations. VCR produced dose-dependent body weight loss, reticulocytopenia, granulocytopenia, elevated plasma alkaline phosphatase, GPT, and GOT activities, and damage to the gastrointestinal epithelium. These reversible changes were most severe during the first 3 days posttreatment. The mouse was comparable to the dog and the monkey in reflecting the target organ toxicity of VCR in humans. Studies with additional antitumor drugs will be required before the overall predictive reliability of this model can be expressed quantitatively.
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PMID:An investigation of the mouse as a model for vincristine toxicity. 688 27

Deferiprone, also known as L1, is an orally active iron chelator that has been studied extensively in clinical trials. The sporadic occurrence of agranulocytosis in association with deferiprone and the highly variable frequency of other possible side effects such as arthralgia have created uncertainty about the true incidence of deferiprone-related complications. A multi-center, 1-year trial was initiated to determine the safety profile of deferiprone. Using the Apotex formulation of deferiprone, 187 patients with thalassemia who were unable or unwilling to use deferoxamine were enrolled in four centers; 162 patients completed one year of therapy. Agranulocytosis (ANC < 500/mm3) occurred in one patient after 15 weeks of treatment, was not accompanied by infection and resolved following treatment with G-CSF. Nine other subjects developed less severe neutropenia (ANC 500-1500/mm3) with the lowest absolute neutrophil count reaching 500-1250/mm3. The neutropenia in these patients developed after 1-50 weeks of therapy, frequently accompanied febrile illnesses, and occurred predominantly in non-splenectomized patients. Reasons other than neutropenia for discontinuing use of deferiprone included nausea (4), voluntary withdrawal (3), high ALT (2), platelet count < 100,000/mm3 (2), low but unconfirmed ANC (1), protocol violation (1) fatigue (1), and depression (1). Mean ALT levels rose within three months of therapy and stabilized thereafter. Arthralgia and nausea and/or vomiting occurred in 6% and 24% of subjects, respectively. In this multi-center trial with weekly monitoring of blood counts, the incidence of agranulocytosis was 0.58 per 100 patient-years, and the frequency of agranulocytosis after one year was 0.5%. These findings support the safety of this formulation of deferiprone, using the careful monitoring system employed in this trial.
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PMID:A multi-center safety trial of the oral iron chelator deferiprone. 966 43

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

In 1997, the Italian Ministry of Health created a special programme for the controlled distribution of deferiprone to collect data and to evaluate its safety and effectiveness in long-term use. Five hundred and thirty-two thalassaemia patients from 86 treatment centres were enrolled in this programme. One hundred and eighty-seven patients (32%) experienced a total of 269 events that led to a temporary interruption or, in some cases, to a discontinuation of treatment. The incidence of agranulocytosis and milder neutropenias were 0.4/100 and 2.1/100 patient-years respectively. Neutropenia occurred predominantly in younger and non-splenectomized patients. Transient alanine transaminase increase, gastrointestinal discomfort and arthralgia were the other most commonly reported events. Ferritin levels showed a significant decrease in time after 3 years of therapy. This is the largest number of deferiprone-treated patients to have been reported to date. These data show that the drug was effective in reducing serum ferritin levels and the incidence of adverse events was not greater than the frequency reported in clinical trials.
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PMID:The safety and effectiveness of deferiprone in a large-scale, 3-year study in Italian patients. 1210 Jan 70

The identification of a safe, orally active iron chelator is critically important for the prevention of morbidity and early death in patients receiving regular red cell transfusions. Based on our findings in a 1-year multicenter, prospective study of the safety and efficacy of deferiprone in patients with thalassemia major, we have extended the treatment period to 4 years. The mean dose of the chelator was 73 mg/kg per day during 531 patient-years. The rates of agranulocytosis (absolute neutrophil count [ANC] < 500 x 10(9)/L) and milder forms of neutropenia (ANC, 500-1500 x 10(9)/L) were 0.2 and 2.8 per 100 patient-years, respectively. Neutropenia occurred significantly more commonly in patients with intact spleens. Gastrointestinal and joint symptoms decreased significantly after the first year of therapy, and led to discontinuation of deferiprone in only one patient in years 2 to 4. The mean alanine aminotransferase (ALT) value of 71 U/L after 4 years of therapy was significantly higher than the baseline value of 61 U/L. Trend analysis showed no increase in the ALT levels or the percentage of patients with ALT levels greater than twice the upper limit of the reference range. Ferritin levels did not change significantly from the values at the time of change from deferoxamine to deferiprone in either the intention-to-treat analysis or in the 84 patients who completed 4 years of therapy. Because of concerns regarding the effectiveness of the studied dose of deferiprone, 47 patients discontinued therapy, whereas 15 patients interrupted therapy because of concerns regarding low iron levels. The results of this study help to define the safety and effectiveness of long-term therapy with deferiprone.
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PMID:Safety and effectiveness of long-term therapy with the oral iron chelator deferiprone. 1276 39


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