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)

Cefuzonam (CZON) which has a broad spectrum on both Gram-negative and Gram-positive bacteria including methicillin-resistant Staphylococcus aureus was evaluated in severe infections associated with hematological disorders. Sixty five patients were treated with CZON. Among them, 56 patients were evaluable for effectiveness. Nine patients were not evaluable because 3 patients were treated with combination of other antibiotics such as ceftizoxime, norfloxacin, ofloxacin, 1 patient was subjected to additional therapy of G-CSF and gamma-globulin, 4 were the patients with other disease than hematologic disorder (3 malignant mesotheliomas, 1 ovarian cancer), and the remaining one was prophylactically treated. Excellent responses were observed in 21 (37.5%) patients, good responses in 11 (19.6%) patients, with an overall efficacy rate of 57.1%. The efficacy rate in septic patients was 80% (4/5), and that in patient whose peripheral granulocytes were continuously below 100/microliters was 60% (3/5). Three patients who suffered from malignant mesothelioma, one patient who suffered from ovarian cancer, one patient who was treated prophylactically were included in the final evaluation of side effects. Side effects were observed in 2 patients (2/61, 3.3%). In a patient of 7 years, mild liver disfunction (GOT/GPT, 46/55) was found in 10 days after CZON treatment was started. In a patient of 65 years, mild appetite loss was identified in 2 days after CZON administration was begun. The liver disfunction was improved soon after the cessation of the treatment. The mild appetite loss disappeared while the treatment was continued. These results showed that CZON was an effective and safe antibiotic for the treatment of severe infections in patients with hematological disorders.
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PMID:[Clinical evaluation of cefuzonam of severe infections in leukemia and related disorders]. 228 6

A combination antibacterial therapy with fosfomycin (FOM) and sulbactam/cefoperazone (SBT/CPZ) was applied to 78 patients with severe infections associated with hematological diseases. In this protocol, FOM was followed by SBT/CPZ and each drug was administered for 1 hour intravenously and consecutively. Among 72 evaluable patients, 43 patients had acute leukemia, myeloblastic or lymphoblastic, 22 had malignant lymphoma, 3 had multiple myeloma, and 4 had other hematological diseases as underlying diseases. Bacterial infections diagnosed were sepsis in 21 patients, suspected sepsis in 47, and other infections in 4. The overall efficacy rate of this treatment was 72.2%, and those for individual infections were 66.7% for sepsis, 74.5% for suspected sepsis, and 75.0% for other infectious diseases. Among 22 bacteria separated from patients with sepsis, 78.6% (11/14 strains) were eradicated by this treatment. This protocol was also effective in 57.1% (8/14) of patients whose granulocyte count was less than 100/mm3 during the course of treatment as well as in 83.3% (15/18) of patients with granulocyte count over 500/mm3. There was no difference in effectiveness between those patients to whom G-CSF was administered and those to whom it was not (17/24, 70.8% vs 35/48, 72.9%). As an adverse reaction, a transient increase of GOT and/or GPT was observed in 2 patients (2.8%). The consecutive administration treatment of FOM and SBT/CPZ is thus an effective and safe regimen for the treatment of patients with hematological diseases complicated by severe infections.
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PMID:[A combined consecutive therapy with fosfomycin and sulbactam/cefoperazone for bacterial infections associated with hematological diseases]. 754 Feb 19

We conducted a multicenter Phase II study of BMS-181339 in patients with ovarian cancer. The facilities participating were 23 in number. The total number of cases registered for the study were 62; 57 of them entered for evaluation in drug efficacy, and 58 cases were evaluable in drug safety. All the cases were previously treated with chemotherapy including platinum-based drugs. The clinical responses of BMS-181339 were as follows: CR, 1 case; PR, 13 cases; MR, 3 cases; NC, 13 cases and PD, 27 cases. The response rate was 24.6% (95% CI: 14.1-37.8%). Histologically, the drug showed its efficacy on serous adenocarcinoma 28.2% (11/39), mucinous adenocarcinoma 20.0% (1/5) and clear cell adenocarcinoma 20.0% (1/5). In regional evaluation, the drug demonstrated its efficacy not only on endopelvic lesions 19.0% (4/21) and abdominal lesions 14.3% (2/14), but also on remote metastatic lesions such as hepatic metastasis 30.8% (4/13) and lung/pleura 33.3% (2/6). The drug also showed its efficacy on the cases 22.9% (8/35) refractory to the platinum-based drugs. Major adverse reactions were fever 63.8% (37/58), alopecia 59.3% (32/54), peripheral nerve disorders 28.1% (16/57) such as numbness of the extremities, nausea/vomiting 24.1% (14/58), arthralgia 20.7% (12/58) and diarrhea 20.7% (12/58) etc.. Abnormal alterations in laboratory test values were an incidence rates of 100% for both leukopenia and neutropenia. However, these symptoms were clinically manageable by transient withdrawal of medication, dose reduction and administration of antibiotics and G-CSF. In addition, decrease in hemoglobin 93.1% (54/58), decrease in platelet counts 31.0% (18/58), elevation in GOT 27.6% (16/58), in GPT 31.0% (18/58) and in LDH 20.7% (12/58) were seen, but no serious organopathy was observed. Thus, we confirmed that BMS-181339 was a clinically useful chemotherapeutic agent in patients with ovarian cancer.
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PMID:[A phase II study of BMS-181339 in patients with ovarian cancer. BMS-181339 Ovarian Cancer Study Group]. 794 92

A phase II study of Paclitaxel in patients with ovarian cancer by 3-hour intravenous infusion was undertaken by a cooperative study group of 30 institutes. Of 66 cases enrolled, 57 cases were evaluable for efficacy, and 63 cases were evaluable for safety. In spite of the fact that all cases for efficacy evaluation were previously treated with chemotherapy including platinum-based drugs, 2 cases of complete response (CR) and 15 cases of partial response (PR) were observed, with a response rate of 29.8% (The 95% confidence interval of response rate was 18.4-43.4%). Paclitaxel also showed 28.2% (11/39) response rate in patients refractory to treatment by platinum-based drugs. Histologically, the response rates were 28.9% (11/38) in serous adenocarcinoma, 40.0% (2/5) in clear cell adenocarcinoma and 25.0% (1/4) in mucinous adenocarcinoma. As the major laboratory abnormalities, leukopenia, neutropenia and decrease in hemoglobin were observed with incidence rates of 98.4% (62/63), 95.2% (59/62) and 85.7% (54/63), respectively. However, these abnormalities were clinically manageable by either withdrawal of medication, administration of antibiotics, G-CSF or metachysis etc. In addition, thrombocytopenia, elevation in GOT and GPT were seen with moderate incidence. Peripheral neuropathy was a major adverse symptom with an incidence of 79.4% (50/63), followed by alopecia, myalgia, arthralgia and fever. However, the majority of these adverse reactions were less than grade 3. From these findings, we confirmed that 3-hour intravenous infusion of Paclitaxel was a clinically useful chemotherapeutic agent in patients with ovarian cancer.
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PMID:[Phase II study of paclitaxel (BMS-181339) in patients with ovarian cancer by 3-hour intravenous infusion]. 871 25

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

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) (lenograstim) was administered to healthy subjects at doses of 2, 5 and 10 micrograms/kg/day for 5 days (twice a day subcutaneously) to examine the optimal dose and schedule of lenograstim in mobilizing peripheral blood progenitor cells (PBSC) for allogeneic transplantation. Lenograstim administration significantly increased CD34+ cells in a dose-related manner. A significant correlation was observed between the maximal post-dosing counts and the pre-dosing baseline counts of CD34+ cells. Peripheral neutrophils increased markedly by seven to 13 times from the baseline to a peak of approximately 40,000/microliter on day 5 for the 5 and 10 micrograms/kg/day doses. After peak serum concentration (Cmax) was attained 4 h following administration, serum G-CSF declined with time in a log-linear fashion. The Cmax and 12 h area-under-the-curve increased dose dependently, but minimum drug level increased up to day 2 and then decreased until day 5. Clearance decreased with increasing dosage at the first dose, and increased significantly at the last dose. We found a highly significant correlation between absolute neutrophil counts and clearance for each dose. Adverse events most frequently occurred on day 6, with increases of alkaline phosphatase and lactate dehydrogenase and onset of bone pain. Increases of aspartate aminotransferase and alanine aminotransferase occurred as delayed events. Platelet count gradually decreased after the end of drug administration to 57% of the pre-dosing count on day 10, but was still within the normal range. These preliminary results suggest that repeated doses of lenograstim induce mobilization of PBSC in a dose-dependent manner and the pre-dosing baseline count of PBSC may predict the post-dosing maximal mobilization. The drug treatment may cause delayed-onset moderate thrombocytopenia and increased transaminase, and the drug clearance changes in a complex manner during repeated dosing.
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PMID:Pharmacokinetics and adverse events following 5-day repeated administration of lenograstim, a recombinant human granulocyte colony-stimulating factor, in healthy subjects. 1110 Feb 72

A 28-year-old man developed cryptogenic hepatitis in January 1999, and treatment with glycyrrhizic acid improved his liver function. From June, however, pancytopenia began to develop gradually. The patient received G-CSF against leukocytopenia (WBC 1,100/microliter, neutrophils 590/microliter) and was transferred to our hospital in August 1999. A diagnosis of hepatitis-associated aplastic anemia was made on the basis of liver dysfunction (AST 156 IU/l, ALT 386 IU/l), hypoplastic bone marrow, and pancytopenia (WBC 4,400/microliter, neutrophils 3,340/microliter under G-CSF administration, Hb 9.8 g/dl, platelets 2.4 x 10(4)/microliter, reticulocytes 4.7 x 10(4)/microliter). Immediately after starting combined therapy with ATG, cyclosporin, and G-CSF, his liver function began to improve and was normalized on day 7. Pancytopenia began to ameliorate on day 9, and blood parameters on day 60 were WBC 4,200/microliter (without G-CSF administration), Hb 12.0 g/dl, platelets 9.0 x 10(4)/microliter, and reticulocytes 4.1 x 10(4)/microliter. Although the prognosis of hepatitis-associated aplastic anemia is generally poor, immunosuppressive therapy was markedly effective for both pancytopenia and hepatic dysfunction in the present case.
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PMID:[Successful combined therapy with ATG, cyclosporin and G-CSF for both liver dysfunction and bone marrow failure in hepatitis-associated aplastic anemia]. 1168 Sep 80

A late phase II clinical trial of amrubicin hydrochloride, a novel synthetic anthracycline derivative anticancer agent, was conducted at 14 institutions nationwide, in patients with non-Hodgkin's lymphoma. In this multi-center collaborative study, doxorubicin hydrochloride was replaced by amrubicin hydrochloride in CHOP therapy, a standard regimen for non-Hodgkin's lymphoma consisting of cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate and prednisolone. A total of 39 patients were enrolled in this study between January 1996 and March 1998. Among them, 37 patients were eligible for this study. The study drugs were administered to patients with non-Hodgkin's lymphoma according to the following schedule: amrubicin hydrochloride (100 mg/m2, body surface area), cyclophosphamide (750 mg/m2) and vincristine sulfate (1.4 mg/m2, a maximal dose of 2.0 mg/body) were administered intravenously on day one, while prednisolone (60 mg/m2/day) was administered orally on days 1 to 5. This cycle of treatment was repeated every three weeks in principle. The efficacy and safety were assessed for 37 eligible patients. The combined rate for CR + CRu was 70.3% (26/37) and the overall response rate (CR + CRu + PR) was 86.5% (32/37). demonstrating that amrubicin hydrochloride was very effective in the treatment of non-Hodgkin's lymphoma. The most frequent adverse reactions that occurred during the study were myelosuppressions: leukopenia and neutropenia, 100% (37/37); and decreases in hemoglobin levels, 81.1% (30/37). Thrombocytopenia, elevations of serum GOT and GPT levels, anorexia, nausea/vomitting, fever, stomatitis and alopecia were also observed. Although leukopenia and neutropenia of grade 3 or higher were noted in 89.2% (33/37) and 94.6% (35/37), respectively, they were controllable by administrations of G-CSF or solely by follow-up observations. One patient developed intestinal paralysis (grade 4) and another developed hematemesis. In conclusion, these results indicate that amrubicin hydrochloride is an effective agent as a component of combination chemotherapy for non-Hodgkin's lymphoma.
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PMID:[Late phase II clinical study of amrubicin hydrochloride, a novel synthetic anthracycline derivative anticancer agent, for malignant lymphoma]. 1172 79

We experienced 4 cases of agranulocytosis due to anti-tuberculosis drugs (rifampicin [RFP], isoniazid [INH], ethambutol [EB], streptomycin [SM] or pyrazinamide [PZA]) among some 6,400 tuberculosis patients who underwent chemotherapy over the past 20 years from 1981 to 2002 in our hospital, and the incidence rate of agranulocytosis was estimated at 0.06%. The 4 cases of agranulocytosis were as follows. CASE 1: A 51-year-old woman with right chest pain and fever was admitted to our hospital on Jan 4, 2001. The white blood cell (WBC) count was 5,200/microliter. The tubercle bacilli were cultured in her sputum. The treatment with INH 0.3, RFP 0.45, EB 0.75, PZA 1.2 g/day, allopurinol and teprenone was started on Jan 13. Pyrazinamide and allopurinol were stopped because of hyper-uric acidemia on Feb 7. Agranulocytosis and eosinophilia (WBC 1,300 [Neut 1%, Ly 57%, Eos 35%]) developed on Feb 13. All drugs were withdrawn and G-CSF drug nartograstim 100 micrograms was injected subcutaneously for 3 days. The WBC recovered to normal level and she was thereafter treated with INH, EB and Levofloxacin (LVFX) without any further trouble. Agranulocytosis in this case was supposed to be due to RFP. CASE 2: A 66-year-old man who had had nephrotic syndrome and hypothyroidism and has been treated with prednisolone 10 mg/day was admitted to our hospital on Aug 9, 2000 because of miliary tuberculosis. The tubercle bacilli were cultured in his sputum and the treatment with INH 0.3, RFP 0.45, and EB 0.75 g/day were started on Aug 10, but it was withdrawn on Aug 17 because of general skin eruption. After re-starting treatment with EB and INH on Aug 24, RFP was added in small dosage (0.05 g) on Oct 12, but agranulomatosis (WBC 2,300/microliter [Neut 2%]) developed on Nov 21, and all drugs were withdrawn again. The G-CSF drug filgrastim was used once subcutaneously, and WBC recovered immediately. He was thereafter treated with INH, EB, LVFX successfully. Agranulocytosis was supposed to be due to RFP. CASE 3: A 60-year-old woman without symptoms had abnormal chest roentgenograph, and consulted with our hospital on Aug 26, 2002. The broncho-alveolar lavage fluid was smear and culture-negative, but PCR-TB positive, and the case was diagnosed as pulmonary tuberculosis. Treatment with INH 0.3, RFP 0.45, EB 0.75, PZA 1.2 g/day, alloprinol 300 mg and rebamipide 300 mg/day was started on Sept. 5, 2002. Late in September, she complained of appetite loss. The laboratory data on Oct 3 revealed WBC 900/microliter (Neut 1%, Ly 94%), aspartate aminotransferase (AST) 199 IU/l, and alanine aminotransferase (ALT) 253 IU/l, showing agranulocytosis and drug-induced hepatitis. The chemotherapy was immediately withdrawn and she was admitted to our hospital on the next day. Glycyrrhizin derivative (SNMC) 40 ml was injected for 5 days, and WBC recovered, and AST and ALT also became normal. CASE 4: A 60-year-old man was admitted to our hospital on March 11, 1981 because pulmonary tuberculosis had recurred. He had been treated with SM, PAS and INH in 1973 for pulmonary tuberculosis. On admission examination of blood count and blood chemistry were normal. Treatment with RFP, INH and SM was started on March 11. He stopped out from the hospital on April 17, but in a few days he returned back with sore throat, lower lip swelling and gingival bleeding. Blood cell count on April 24 showed pancytopenia with RBC 226, Hb 7.5, WBC 800 (Ly 96%, Eos 4%) and Plt 10,000/microliter. The bone-marrow showed NCC (nuceated cell count) of 5,500, and megakaryocyte 0. Thereafter ground glass appearance shadows were seen on the whole lung field, and he died May 26. Autopsy showed generalized aspergillosis. It was strongly suspected that either of RFP, INH or SM was responsible for his pancytopenia. We collected another 10 cases of agranulocytosis due to anti-tuberculosis drugs in the world wide literature, and found men/women ratio 5/8 (in one case gender was not known), the duration of chemotherapy before appearance of agranulocytosis 1-3 months, no change in the lymphocyte count of the peripheral blood, and the accompanying of another allergic signs such as skin eruption, blood eosinophilia or drug-induced hepatitis in some cases, and these findings suggest that the mechanism of agranulocytosis due to anti-tuberculosis drugs was allergic in nature.
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PMID:[Agranulocytosis due to anti-tuberculosis drugs including isoniazid (INH) and rifampicin (RFP)--a report of four cases and review of the literature]. 1467 45

Since liver regeneration after partial hepatectomy (PHx) is known to improve by pretreatment with recombinant human G-CSF (rhG-CSF), we investigated the mechanism by evaluating the distribution and activity of sinusoidal NK cells. F344 rats were treated with rhG-CSF (250 microg/kg/day) for 5 days before PHx. Pretreatment with rhG-CSF improved the serum ALT levels and DNA biosynthesis of the remnant liver tissues at 20 h after PHx. Notably, the rhG-CSF pretreatment decreased the number of NK cells in the liver determined by immunohistochemistry using anti-NKR-P1A mAb before and at 20 h after PHx with no significant change in the NK activity per cell base, while also increasing the number of NK cells in the peripheral blood detected by flow cytometry. The rhG-CSF induced a pre-PHx downregulation of the IL-12p70 protein levels, while also promoting the post-PHx reduction of the protein levels of IL-12p70 and IFN-gamma. Conversely, rhG-CSF had no effect on the pre-PHx mRNA levels or the PHx-induced upregulation of mRNA levels of TNF-alpha, IL-1beta, IL-6, TGF-beta, IL-10, HGF, and c-Met determined by real-time RT-PCR. These results strongly suggest that rhG-CSF-induced facilitation of liver regeneration is achieved by immunoregulation through the intrahepatic IL-12 downregulation and evacuation of sinusoidal NK cells.
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PMID:G-CSF-induced evacuation of sinusoidal NK cells and the facilitation of liver regeneration in a partial hepatectomy. 1671


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