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Biomedical subjects

M Takamoto

Publications and source records attributed to M Takamoto.

At least 91 records · Page 5Linked to original sources

[Clinical trial of forphenicinol for the lung infection with Mycobacterium avium, Mycobacterium intracellulare complex].

Clinical evaluation of forphenicinol, a low molecular weight immunomodulator, in patients with Mycobacterium avium, Mycobacterium intracellulare complex pulmonary infections has been conducted in a multicenter trial participated by 9 institutions in Kyushu during a period of 12 months from July 1982 to August 1983. Forphenicinol was administered for 6 months without changing the regimen of antituberculous drugs used previously. The following results were obtained. 1. Ten out of 33 eligible patients were evaluated as showing good responses; In 5 of them, elimination of M. avium, M. intracellulare complex from sputum was observed. In the other 5 patients, number of bacilli excreted was decreased significantly after treatment. 2. All of the cases with good responses were those which were simultaneously administered with antituberculous drugs. 3. Patients with thick-walled cavities, following cured tuberculosis, which was superimposed with M. avium, M. intracellulare complex, were poorly responded to forphenicinol. 4. Side effects were observed in 3 out of 41 patients; 1 case each with fever, abdominal distension and anorexia. No abnormalities in laboratory test values were observed.

Adult↗

[Clindamycin-2-phosphate in the treatment of respiratory infections and its distribution into pleural effusion].

We treated pneumonia due to anaerobic bacteria, Mycoplasma pneumonia, and other type of pneumonia with clindamycin-2-phosphate (CLDM-P) and studied the distribution of the drug into pleural effusion. The obtained results are summarized as follows. 1. CLDM-P showed excellent effects in all the treated cases of pneumonia due to anaerobic bacteria and Mycoplasma pneumonia. But the success rate was 50% in cases of other type of pneumonia. We suggest that the drug must be used in due consideration of the types of causative bacteria. 2. Five cases which had developed pleural effusions were treated with intravenous drip of CLDM-P 1,200 mg in 200 ml electrolytic solution to see the distribution into pleural effusions. The results showed that the distribution ratio was 9.0% on the average. Peak levels were 1.86-6.07 micrograms/ml and the concentration was as high as 1.28 micrograms/ml on the average 24 hours after administration.

Adolescent↗

[Clinical evaluation of cefoperazone in lower respiratory tract infections].

Clinical evaluation and kinetics in serum of cefoperazone (CPZ) in patients with lower respiratory tract infections have been conducted as a multicenter trial participated by 20 institutions in Kyushu area during a period of 8 months from October 1984 to May 1985. Mean serum CPZ levels up to 4 hours following the end of intravenous infusion of either 1 or 2 g CPZ remained higher than the MIC80 of CPZ against major causative organisms of lower respiratory tract infections such as H. influenzae, P. aeruginosa, K. pneumoniae, and S. pneumoniae. Serum half-lives of CPZ following intravenous infusion were prolonged in the elderly and in patients who showed moderate liver or kidney dysfunction, but did not exceed twofold of normal value. Clinical efficacy rates of CPZ were 82.9% (34/41) against pneumonia, 80% (4/5) against lung abscess, 88.9% (32/36) against acute exacerbation of chronic bronchitis, 66.7% (2/3) against panbronchiolitis, 100% (1/1) against acute bronchitis, and 85.7% (12/14), 64.3% (9/14) and 70.0% (7/10) against infections concurrent to chronic respiratory diseases, pulmonary emphysema and bronchiectasis, respectively. The overall efficacy rate was 81.5% (101/124). Bacteriological eradication rates against P. aeruginosa, H. influenzae and S. pneumoniae were 60% (6/10), 88.9% (8/9) and 100% (3/3), respectively. The overall eradication rate including polymicrobial infection was 67.5% (27/40). The clinical efficacy rate of CPZ in patients with underlying diseases such as lung cancer, pulmonary tuberculosis, and pneumoconiosis, etc. was not significantly different from the efficacy rate in patients without these underlying diseases. Of 20 patients who failed to respond to previous antibiotic treatments, 13 were effectively treated by CPZ. Adverse reactions occurred in 6.7% (11/164) of the patients, and consisted primarily of rash, fever, diarrhea and loose stool. Laboratory abnormalities were seen in 5 patients during the study. These included elevations of S-GOT and S-GPT, eosinophilia and neutropenia. CPZ is a very useful drug in the treatment of lower respiratory tract infections because of its excellent clinical efficacy and rare incidence of abnormal accumulations in sera following the recommended 2-4 g/day administration even in the elderly.

Adult↗

[Fundamental and clinical studies on forphenicinol, a small-molecular immunomodulator].

Forphenicinol , a small-molecular immunomodulator, was orally administered to 10 long-term hospitalized patients with decreased pulmonary function, mainly, due to obsolete tuberculosis. The patients were grouped equally into 2, the first group received 50 mg of forphenicinol /day for 4 weeks and the second group received forphenicinol for a total period of 1 year, according to the following dose-schedule; 100 mg/day for the first 2 months, 400 mg/day for the next 6 months and 200 mg/day for the last 4 months. Investigations were made on the serum levels and safety of forphenicinol in all of these patients. The results of the investigations were as follows. Peak levels of forphenicinol were attained, in most cases, 2 hours after the administration and the average peak levels on the 14th day were 1.37 micrograms/ml for the dose of 50 mg/day, 5.02 micrograms/ml for 100 mg/day, 7.49 micrograms/ml for 200 mg/day and 15.02 micrograms/ml for 400 mg/day. There was no difference between the serum peak levels on the 1st and 14th days, in the patients who received forphenicinol at the dose of 50 or 100 mg/day. This finding led us to conclude that forphenicinol may not be accumulated in the body when it is administered repeatedly. Neither any side effects nor any abnormal values in the laboratory analysis of samples were observed for forphenicinol . The following improvement were observed, in the patients who received forphenicinol on a long-term basis (1 year); diminution of thick-walled cavity in 1 patient with atypical mycobacteriosis and in another patient with drug-resistant Mycobacterium tuberculosis, negative sputum culture for bacteria was observed during this whole period of forphenicinol treatment.

Adjuvants, Immunologic↗

[Clinical trial of netilmicin in infections of respiratory organs and studies on its penetration into pleural fluid II. (author's transl)].

To 10 cases with respiratory infections, 200 mg, twice daily, of netilmicin was administered without other antibiotics and the following results were obtained. 1) Netilmicin was administered to 2 cases of pneumonia and 8 cases of bronchitis for 7 to 30 days, and 4 remarkably effective and 6 effective cases were observed, that is, netilmicin was effective in all cases. 2) Abnormal laboratory test values were found in 2 cases; 1 case showed slightly elevated creatinine value, and 1 case showed slightly increase GTP value, and these values were normalized rapidly without any treatment after discontinuation of netilmicin administration. Netilmicin 100 mg was intramuscularly injected to 15 patients with pleural effusion to see the time-course distribution of the drug to serum and to pleural fluid by determining the concentration of netilmicin. 1) Netilmicin concentrations in serum reached the peak at 30 minutes after the intramuscular injection and it gradually decreased, while in the pleural fluid, it reached the peak at 3 hours after the injection, and the peak value in the pleural fluid in average was 2.63 +/- 1.98 micrograms/ml, and it was still detectable at 24 hours after the injection. 2) The ratio of netilmicin concentrations in the serum and pleural fluid at the peak was 31.7 +/- 23.4%, and distribution of netilmicin into the pleural fluid was considered to be high enough.

Adult↗

Altered resistance to Listeria monocytogenes in diabetic mice.

Resistance to Listeria monocytogenes (L.M.) in diabetic state was studied using streptozotocin (SZ)-induced diabetic mice. SZ-diabetic mice showed an enhanced resistance to primary listerial infection with a sublethal dose of inoculum, whereas there was no difference between normal and diabetic hosts when challenged with a lethal dose. The growth of L.M. in diabetic mice was inhibited at an early stage of infection. However viable Listeria survived in diabetic mice at a later stage, suggesting the trend of persisting infection. Such enhanced resistance to L.M. in diabetic mice was associated with increased rate of spreading of peritoneal macrophages and with reduction in the level of delayed type hypersensitivity (DTH) to L.M. Therefore, it seemed likely that the enhanced resistance to Listeria in diabetic mice would be due to nonspecifically activated macrophages. Secondary challenge in the immunized animals and transfer experiment with immune spleen cells revealed that the development of protective immunity in diabetic mice was inferior to that in normal mice. Treatment with insulin could hardly influence the altered resistance to L.M. in diabetic mice.

Animals↗

Reduced resistance to Pseudomonas septicaemia in diabetic mice.

Antibacterial resistance in a diabetic state was studied using experimental Pseudomonas infection in streptozotocin (SZ) induced diabetic mice. The results obtained were as follows: (1) there was no difference in acute death rate between normal and diabetic mice when infected with Pseudomonas aeruginosa. However, a significant increase in the number of bacteria in the kidney and liver occurred at a later stage of infection in diabetic mice. (2) Active immunization with a phenolized vaccine resulted in 100% survival in either normal or diabetic mice; otherwise challenge was lethal. However, the organs examined in diabetic vaccinated mice contained distinctly increased numbers of bacteria as compared with normal vaccinated mice 7 days after infection. (3) There were no significant differences in antibody titre between normal and diabetic ice after infection, but passive protection with immune serum from diabetic vaccinated mice was less effective than that from vaccinated mice. Furthermore, immune serum from normal vaccinated mice exerted protective action less efficiently in diabetic recipients than in normal recipients. (4) The bactericidal effect of peripheral whole blood was apparently lower in diabetic mice than in normal mice. (5) Treatment with insulin restored such reduced resistance to Pseudomonas infection in diabetic mice. These findings suggest that the decreased resistance to Pseudomonas infection in diabetic mice should be ascribed to impaired function of antibody, abnormalities in phagocytic cells and disturbed microcirculation caused by the insulin-deficient state.

Animals↗

Distant metastasis facilitated by BCG: spread of tumour cells injected in the BCG-primed site.

Tumour metastasis in BCG-pretreated mice was studied using a methylcholanthrene-induced fibrosarcoma in C3H/He mice. When tumour cells were injected into the BCG-primed site, distant metastasis occurred in the lungs and the popliteal lymph node, through this tumour did not metastasize in normal mice. Such metastases were increased in proportion to the number of tumour cells injected into the BCG-primed site, and developed soon after tumour challenge. Concomitant immunity developed well in the mice bearing such metastases, but did not inhibit metastatic growth. Experiments using 125I-labelled SRBC or tumour cells revealed that such cells egressed rapidly from the BCG-primed site. When the tumour was inoculated into the contralateral foot to the BCG-primed site, the incidence and the number of metastases was reduced. Furthermore, BCG infection induced an increase of platelet count. I.v. injection of this tumour induced marked thrombocytopenia in normal mice. Administration of pentoxifylline, a methylxanthine derivative before tumour challenge reduced such metastases. These findings suggest that the changes in peripheral blood, such as increased platelet count and increased release of tumour cells from the injection site, facilitated distant metastasis in BCG-pretreated mice.

Animals↗

Immunologic features of mice with streptozotocin-induced diabetes: depression of their immune responses to sheep red blood cells.

The immune responsiveness in streptozotocin (SZ)-induced diabetic mice was studied using the immune responses to sheep red blood cells (SRBC) as an indicator system. In SZ-diabetic mice, the weights of such lymphoid organs as the thymus and spleen were significantly decreased with time after SZ administration, whereas the weight of liver was markedly increased. In SZ-diabetic mice, the level of delayed type hypersensitivity (DTH) to SRBC was not lower than that in normal controls in most cases, although the level of DTH was significantly depressed, on occasion, in SZ-diabetic mice. In contrast, antibody-forming activity, measured as the number of plaque-forming cells (PFC), was markedly decreased in SZ-diabetic mice. It seems that antibody production is more profoundly depressed than is DTH in SZ-diabetic mice. The transfer of normal thymus and bone marrow cells into SZ-diabetic mice caused only a partial restoration of PFC activity. When normal spleen cells were transferred into diabetic irradiated mice, proliferation of spleen cells and production of splenic PFC was greatly reduced as compared with normal irradiated mice. Treatment with insulin completely reversed such depression in the transfer system. These findings suggest that the chronic insulin-deficient diabetic state caused a depression and delay in the proliferation and differentiation of lymphoid cells.

Animals↗