Biomedical subjects
Publications and source records attributed to A Horiuchi.
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Micronomicin (MCR) at a daily dose of 120 to 360 mg was administered to patients with severe infections who had hematopoietic disorders as underlying diseases. Efficacy and safety of the drug were evaluated. The underlying diseases in the 56 patients included in the evaluation of efficacy were acute myelocytic leukemia (24 cases), acute lymphocytic leukemia (8), acute promyelocytic leukemia (6), acute monomyelocytic leukemia (4), acute monocytic leukemia (1), erythroleukemia (1), chronic myelocytic leukemia-blastic crisis (4), malignant lymphoma (3), aplastic anemia (2), and others (3). The infections were septicemia in 9 patients, suspected septicemia in 48, respiratory tract infection in 7, and perianal abscess in 2. The clinical efficacy of MCR was 'excellent' in 12 patients, 'good' in 17, 'fair' in 7, 'poor' in 30 for an efficacy rate of 43.9%. The efficacy rate classified according to infections was 22.2% in septicemia, 56.3% in suspected septicemia. The organisms isolated from the patients with septicemia were Escherichia coli in 2, Klebsiella pneumoniae in 2, Pseudomonas aeruginosa in 1, alpha-Streptococcus in 1, Serratia marcescens in 1, and Acinetobacter sp. in 1. The efficacy rate was 15.4% in the 13 patients whose causative organisms were identified. The efficacy rate for patients who had failed to respond to prior antibiotic therapy was 43.9%. The efficacy rate in patients (34 cases) with an initial neutrophil count less than 100/microliter was 44.1%. Side effect which might have been caused by MCR was skin eruption in only one episode among 83 episodes those were evaluated for safety.
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Twenty-five patients with malignant lymphomas were treated with etoposide oral capsule 200mg/day for 5 days, repeated 3-4-weekly. Twenty-one cases were evaluable. CR was achieved in four cases (19.0%) and PR in six cases (28.6%). The most serious adverse effect of the drug was leukopenia. In one patient (6.7%) the leukocyte count was lower than 1,000/mm3. Gastrointestinal toxicities such as anorexia, nausea, vomiting and diarrhea occurred in about 66.7% of patients but were not serious; alopecia was observed in 65.2%. In conclusion, etoposide is considered effective for malignant lymphomas.
One hundred and nine patients with infection accompanying hematologic disorders including leukemia and lymphoma were treated with aztreonam (AZT). Of the 90 patients in whom the efficacy could be evaluated, 17 (18.9%) responded markedly and 29 (32.2%) moderately, the effective rate being 51.1%. The efficacy rate classified according to infections was 25% in septicemia, 46.3% in suspected septicemia, 57.1% in pneumonia and 100% in urinary tract infection. The efficacy rate to the Gram-negative bacteria was 78.9% and to the Gram-positive bacteria was 20.0%. In 4 (66.7%) out of 6 patients in whom P. aeruginosa was the causative organism, AZT was effective. The efficacy rate was 52.2% in the 23 patients whose causative organisms were identified and 50.7% in 67 patients whose causative organisms were not identified. There was no significant difference in the efficacy rate between the patients who failed to respond to prior antibiotic therapy (53.6%) and those treated with AZT from the beginning. The initial neutrophil count did not affect the efficacy rate. Side effects which might have been caused by AZT were eruption and fever in 4 patients. Hepatic disorders and eosinophilia were observed in 7 patients. However, the relationship between AZT and these abnormal findings was not established. These results indicate that AZT is an effective and safe antibiotic for the treatment of infections accompanying hematologic disorders.
The effect of immunotherapy with a protein-bound polysaccharide preparation termed PSK on remission duration and survival of adults with acute nonlymphocytic leukemia (ANLL) was studied in a prospective randomized cooperative trial. After having achieved complete remission and receiving a consolidation therapy, 73 patients were randomized either to maintenance chemotherapy or to maintenance chemotherapy plus immunotherapy with PSK. Ultimately 36 patients in the chemotherapy group and 31 in the chemoimmunotherapy group were evaluable. Six months after the last entry, immunotherapy with PSK showed a borderline beneficial effect on remission duration (P = 0.089) and on duration of survival (P = 0.062). When the data were analyzed 12, 18, and 24 months after the last entry there were no significant differences in duration of remission and survival between the two groups. However, analysis of the data of patients who had maintained complete remission for more than 270 days revealed that immunotherapy had a suggestive beneficial effect (P = 0.105), prolonging the 50% remission period by 418 days (885 vs 467 days). Thus, immunotherapy with PSK seems to be active in the treatment of adult ANLL when used for maintenance therapy in combination with chemotherapy, especially in patients with a good prognosis.
The pharmacokinetics of cefotaxime were studied in 13 patients on haemodialysis or continuous ambulatory peritoneal dialysis (CAPD). One gram of cefotaxime was administered intravenously or intraperitoneally. In the haemodialysis patients, the serum concentration after 4h was 9.4 mg/l and the T1/2 was 1.31 h. The 6-h value and T1/2 in the CAPD (intravenous) patients were 4.5 mg/l and 1.59 hours, while the peak value in the dialysate was 11.6 mg/l. In the CAPD (intraperitoneal) patients, the cefotaxime concentration in the dialysate was 157 mg/l after 6 h and the peak value in the serum was 9.1 mg/l. Since cefotaxime is easily removed from the blood by both the haemodialysis and CAPD methods, accumulation of the drug in patients undergoing dialysis is unlikely to occur.
One hundred patients with severe infections associated with hematologic disorders, including leukemia and lymphoma, were treated with ceftizoxime (CZX) in daily doses of 4 approximately 9 g for an average of 8.9 days. In the 84 patients who completed the trial, response was excellent in 27 (32.1%) and moderate in 25 (29.8%). The rate of effectiveness was 61.9%. The only side effect seen during the treatment was skin rash in 3 patients. Hepatic disorders were observed in 5 patients. The relation between CZX and these abnormal findings was not established. These results indicate that CZX is a therapeutically effective and safe antibiotic for the treatment of severe infections in patients with underlying hematologic disorders.
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