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 ceftizoxime, a new cephalosporin, were carried out in our department. The following results were obtained. 1. Antibacterial activity. Antibacterial activity of ceftizoxime against 7 strains of E. coli, 6 strains of Klebsiella, 6 strains of H. influenzae, 7 strains of E. cloacae and 10 strains of S. aureus, recently isolated from patients, was compared with that of cefotiam, cefmetazole and cefazolin. Ceftizoxime was more active than the other antibiotics against E. coli, Klebsiella, H. influenzae and E. cloacae, but less active against S. aureus. 2. Urinary excretion. Urinary excretion was measured in 2 cases with normal renal function after dosing with 750 mg (35 mg/kg) and 350 mg (17 mg/kg) of ceftizoxime by intravenous injections. Urinary recovery rates within 6 hours were 97% and 82% respectively. 3. Clinical study. Eighteen children with the following bacterial infections were treated with ceftizoxime; respiratory tract infection (13), acute otitis media (1), acute intervertebral chondritis and tonsillitis (1), chronic cystitis (1), subcutaneous abscess (1) and chronic bacteremia (1). The dosage was 69--147 mg/kg q.i.d. by intravenous injection. The duration of administration was from 3 to 32 days. The clinical results were excellent in 4 cases, good in 13 cases and fair in 1 case of chronic bacteremia. The overall effectiveness rate was 94%. Slight elevation of GPT in 1 case and leukopenia (neutropenia) in 1 case were observed, but returned to the normal range immediately after discontinuation of dosing. It is considered that ceftizoxime is one of the useful first choice antibiotics used for children with bacterial infections.
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PMID:[Clinical studies on ceftizoxime in pediatric field (author's transl)]. 627 3

Ceftazidime ( CAZ ) is a newly developed cephalosporin. Clinical studies on this drug was carried out and the results were as follows. Twenty-nine patients (acute purulent tonsillitis 2, acute bronchitis 1, pneumonia 15, acute purulent lymphadenitis 2, pyoderma 1, skin abscess 2 and urinary tract infection 6) were treated with CAZ in doses of 42-1 mg/kg (mean 59 mg/kg) divided 2-3 times per day for 3-10 days (mean 5.7 days) intravenously. The overall efficacy rate was 96.6%. As to adverse reaction, drug fever was observed in 1 patient. Abnormal laboratory data were noted in 4 cases (elevation of serum GOT, GPT and BUN in 1, elevation of serum GOT and GPT in 1, elevation of BUN in 1 and leukopenia in 1).
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PMID:[Clinical studies on ceftazidime in the pediatric field]. 637 48

Postoperative immunochemotherapy with mitomycin C (MMC), 5-fluorouracil (5-FU) and OK-432 was evaluated as adjuvant therapy for curative resection in the cases of gastric cancer. One hundred and twenty-two patients (28 were excluded) were randomly assigned to 3 groups: Group A-MMC and 5-FU (28 cases); Group B-MMC, 5-FU and OK-432 (33 cases); Group C-control (33 cases). There were no differences in the back ground factors influencing survival time among each group. Group B showed better results in survival rate and disease free interval as compared with Group A or C. Minor and reversible side effects such as enterogastric disorder, leukopenia (less than 3000/mm3), thrombo cytopenia (less than 7 X 10(4)/mm3) and elevation of serum transaminase (S-GPT greater than or equal to 100 unit) were equivalently observed in frequency in each Group A and B, but they were milder in Group B than Group A.
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PMID:[Adjuvant immunochemotherapy combined with OK-432 following surgery of stomach cancer]. 640 9

A controlled clinical trial of surgical adjuvant immunochemotherapy of gastric cancer was started in July, 1974 involving twelve institutes (Chairman; T. Kondo) in Japan. Patients with gastric cancer undergone curative resection were eligible. These patients were divided into 3 groups; Group A, mitomycin C (MMC) + 5-fluorouracil (5-FU): Group B, MMC + 5-FU + PSK or MMC + 5-FU + OK-432; and Group C, surgery alone. Of 1412 patients accumulated up to December 1977, 848 cases were evaluable: Group A-264 cases, group B-290 and group C-294. Side effects such as leukopenia, thrombopenia, elevated GOT and GPT, albuminuria and digestive disorders, were observed in 54 cases (20.5%) of group A and in 59 cases (20.3%) of group B. The 3-year survival rates of total cases were 79.2% with group A, 77.0% with group B and 85.2% with group C. The 2-year survival rates of histological stage II cases were 93.4% with group A, 90.5% with group B and 80.7% with group C. The difference in survival rate between A and C (12.7%) was statistically significant (p less than 0.05). The efficacy was not related to the histological type of gastric cancer. Adjuvant immunochemotherapy using OK-432 was significantly effective on a 1-year survival rate of stage IV gastric cancer.
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PMID:[Cooperative studies on surgical adjuvant immunochemotherapy for prevention of postoperative recurrence of gastric cancer]. 642 Dec 43

Laboratory and clinical studies of cefoperazone (CPZ), a new semisynthetic cephalosporin, were investigated and following results were obtained. (1) Blood level: CPZ was given intravenous dose of 25 mg/kg and 50 mg/kg to each 3 children. In the former, the blood level of 15 minutes after injection was 194.2 mcg/ml on average and the half life was 106.2 minutes. In the latter, the blood level was 320.0 mcg/ml on average and half life was 102.2 minutes. (2) Urinary concentration: In the cases of the dose of 25 mg/kg, 35.9% of CPZ was recovered on average from the urine within 6 hours after injection, and the urinary concentration reached to 2,148.6 mcg/ml (0 approximately 2 hours). And in the cases of the dose of 50 mcg/kg, the recovery rate in urine was 43.6%, and the urinary concentration was 3,008.3 mcg/ml. (3) Cerebrospinal fluid level: CSF level was determined in a patient with bacterial meningitis by S. pneumoniae. Ninety mg/kg of CPZ were given intravenous injection. After 60 minutes CSF level was 3.35 mcg/ml, and after 80 minutes the blood level was 192.0 mcg/ml. (4) Bacteriological evaluation: Against 164 strains isolated clinical specimens, the bacteriological evaluation on CPZ was performed in comparison with cefotaxime (CTX), cefazolin (CEZ) and piperacillin (PIPC) by inoculum size of 10(8) cells/ml. CPZ showed antibacterial activity against Gram-negative bacteria almost similar to CTX and PIPC. (5) CLINICAL RESULTS: CPZ was given 48.3 approximately 360 mg/kg/day (average 146.1 mg/kg/day) by intravenous route to 46 patients with various infection. The overall efficacy rate was 80.4%. The rate of bacteriological effectiveness was 78.9% in 19 cases. (6) Side effects: As side effects, diarrhea, fever, rash, urticaria, leukopenia, eosinophilia, elevation of GOT, GPT, and LDH were observed, but not seriously.
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PMID:[Laboratory and clinical studies on cefoperazone in pediatrics treatment (author's transl)]. 645 44

A Phase II study of vindesine was carried out by the Vindesine Study Group in 130 patients with hematological malignancies: mainly 3 mg/body (about 2 mg/m2) of vindesine was administered once weekly by bolus injection. In 122 evaluable patients who had been heavily pretreated with vincristine and/or others, remissions were observed in patients with acute lymphocytic leukemia, blastic crisis of chronic myeloid leukemia, malignant lymphoma and other leukemias. The overall response rate was 39.3% including 20 complete and 28 partial remissions. No remissions were obtained in acute nonlymphocytic leukemia and multiple myeloma. All patients were evaluable for toxicity: Leukopenia occurred in 64.9%; peripheral neuropathy in 24.6%; GPT and GOT elevation in 20.7% and in 10.8%; alopecia in 11.5%; gastrointestinal disturbance in 10.8%; and fever in 5.4%. The treatment with vindesine was generally well tolerated, although in five out of 130 patients (3.8%) the treatment was discontinued due to convulsion, feeling of abdominal distention plus constipation, paralytic ileus, dysuria plus constipation, or interstitial pneumonia. Leukopenia and peripheral neuropathy appeared to be dose-limiting factors.
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PMID:[Phase II study of vindesine in hematological malignancies]. 658 Aug 41

Fourteen patients with advanced malignant melanoma were treated with a combination chemotherapy consisting of ACNU 100 mg/m2 i.v. on Day 1 in 6 week intervals and DTIC 200 mg/m2 i.v. on Days 1 to 5 at 3 week intervals. Four patients had prior chemotherapy and 2 had prior immunotherapy. Excluding 4 patients received the regimen for adjuvant chemotherapy, 10 of 14 patients were evaluable for response. There were 3 patients of partial responses, 3 minor responses, 1 no change, and 3 progressive diseases. The durations of partial responses were 1, 1, and 8 months, respectively, while the survival times in these patients were 5, 21, and 10 months, respectively. Leukopenia less than 4,000/cmm occurred in 10 of 14 patients (71%) and thrombocytopenia less than 100 X 10(3)/cmm in 9 of 14 patients (64%), moreover, these hematologic toxicities were cumulative. Serum GOT and GPT elevated to 3,460 mu/ml and 1,365 mu/ml, respectively in one patient, but this returned to a normal level one month later. Nausea and vomiting were mild to severe in 12 of 14 patients, being most marked on Day 1 and decreasing intensity during the next several days. Other non-hematologic toxicities including skin rash, fever, and phlebitis were noted in each one patient, respectively. Hematologic toxicity of this regimen was a dose limiting toxicity; therefore, intensive supportive therapy to prevent infection and hemorrhage is essential for the management of the patients during this chemotherapy.
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PMID:[A combination chemotherapy of ACNU and DTIC for advanced malignant melanoma]. 696 41

The roles of neutrophils (PMNs) and Kupffer cells in hepatotoxicity caused by allyl alcohol in rats in vivo were examined. To test the involvement of PMNs in the response to allyl alcohol, the number of circulating PMNs was reduced to < 500/microliter by treatment with immunoglobulin (Ig) isolated from serum of rabbits treated with rat PMNs (anti-PMN Ig). Rats received anti-PMN Ig or control Ig 6 h before and 6 h after administration of allyl alcohol (40 mg/kg, i.p.). Hepatotoxicity was assessed 18 h after allyl alcohol administration. In rats pretreated with control Ig, treatment with allyl alcohol resulted in hepatotoxicity as evidenced by an increase in the activity of alanine aminotransferase (ALT) in serum. Neutropenia did not attenuate hepatic injury caused by allyl alcohol. Leukopenia induced by pretreatment with cyclophosphamide also did not influence the hepatotoxic response to allyl alcohol. To inhibit the function of Kupffer cells, animals were treated with gadolinium chloride (GdCl3; 10 mg/kg, i.v.) 24 h before administration of allyl alcohol. This dose of GdCl3 decreased in situ clearance of colloidal carbon by 64%. Despite the inhibition of Kupffer cell function, ALT activity in serum was not different in allyl alcohol-treated rats pretreated with GdCl3 and those pretreated with saline vehicle. Histopathologic evaluation of the livers confirmed a lack of protective effect of GdCl3. These results suggest that neither neutrophils nor Kupffer cells play a major role in liver injury due to allyl alcohol.
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PMID:Depletion of neutrophils and modulation of Kupffer cell function in allyl alcohol-induced hepatotoxicity. 776 5

The clinical phase I study of TNP-351, an antifolate drug having a novel structure, was performed through a multicenter cooperative program in 40 patients with solid tumors. The test drug was used on dosage schedules of single and daily doses for 5 or 3 days (by intravenous drip over 30 minutes, respectively). From the daily administration for 5 days, severe adverse reactions such as myelosuppression, became manifest at 5 mg/m2 (1n). This schedule was then switched to daily administration for 3 days. Administration of the test drug was initiated at a dose of 5 mg/m2. On a single-dose schedule, the dose was increased up to 100 mg/m2 (20 n), and on the 3-day daily administration schedule, up to 10.8 mg/m2 (2.2 n). Consequently, 26 of the study patients received single doses; three of them the 5-day daily administration, and 11 the 3-day daily administration. The dose-limiting factors were leukopenia and thrombopenia on both the single-dose and 3-day daily administration schedules. MTD was 100 mg/m2, and MAD, 75 mg/m2 for the single-dose schedule; and 10.8 mg/m2 and 9 mg/m2 for the 3-day daily administration schedule. WBC and platelet counts fell to nadirs at 1-2 weeks on either the single-dose or 3-day daily administration schedule, and it took the respective parameters about 1 week to recover. Subjective and objective adverse reactions to the test drug consisted of digestive tract disorders manifested as stomatitis, anorexia, nausea and vomiting; and laboratory abnormalities such as elevations of GOT and GPT in addition to the myelosuppression. Many of these adverse reactions subsided within 3 weeks after initiation of TNP-351 treatment. On the single-dose schedule, the test drug occurred chiefly in unchanged form in the blood, and in this form it disappeared from the blood biphasically with an alpha phase of 0.29-0.95 hours, and a beta phase of 7.8-14.4 hours. This disappearance pattern did not vary with an increase in dose. The 24-hour urinary excretion rate of the unchanged form amounted to 42-62% of the administered doses. On the 3-day daily administration schedule, the test drug was not accumulated in vivo. In the present study, two patients with malignant fibrous histiocytoma responded to the test drug with tumor regression. The results suggested that the recommended dosage regimen for the clinical early phase II study of the test drug should comprise a course of 9 mg/m2/day (by intravenous drip infusion over 30 minutes) every day for 3 days, which should be repeated every 3 weeks.
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PMID:[The clinical phase I study of TNP-351. The TNP-351 Research Committee]. 785 2

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


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