Biomedical subjects
Publications and source records attributed to T Takubo.
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The clinical effectiveness of bioclean rooms was studied in relation to prevention of infection during treatment for induction of remission of acute leukemia. According to the steps in clean patient care, patients were divided into three groups, Group A consisting of 106 patients who were accommodated in laminar air flow (LAF) rooms under strictly clean nursing, Group B consisting of 99 patients who were treated in disinfected rooms with LAF without any clean nursing techniques and Group C consisting of 188 patients who stayed in conventional wards. Since all patients were treated with antileukemic drugs and preventive administration of antimicrobial drugs under the same regimen, any difference between groups should be attributable to LAF or LAF and clean nursing. A marked and stepwise reduction in the incidence of infection between Groups A, B and C was observed. A statistically significant reduction in pneumonia, upper respiratory tract infection, periproctitis and skin abscesses was also observed in Groups A and B. As to the causative organisms, a relative increase in incidence of infections caused by Pseudomonas aeruginosa and Escherichia coli and a decrease in those caused by Proteus and fungi were observed in Groups A and B, as compared with Group C. These data suggest that pneumonia etc. may be exogenous infections and that Proteus and fungi are exogenous organisms, while Pseudomonas aeruginosa and Escherichia coli are endogenous bacteria. These data seem very helpful for setting up several steps in bioclean rooms for effective and economic patient care.
A total of 48 patients with various malignant disorders, mostly from hemopoietic organs, entered to phase I study of MCNU given orally. Fifty-six percent of the patients given MCNU at the doses of 50-125 mg/m2 complained of gastrointestinal symptoms including nausea and vomiting, which were however mild and well tolerated. In the following study employing administration of 50 mg/day of MCNU for consecutive 2-6 days, the gastrointestinal toxicities were reduced to 26.1%, and hematological toxicities of delayed leukopenia and thrombocytopenia were derived 4-6 weeks after oral intake of the drug. The hematological recovery required 1-2 weeks after the nadir of leukocyte and thrombocyte count. A recommended dose for phase II study of MCNU by the route of oral administration was 50 mg/body/day for consecutive 4-6 days in every 8 weeks interval. The peak value of blood concentration of MCNU was obtained 60-120 minutes after p.o. administration at the doses of 50-100 mg. Elimination half-life was estimated to be 40-45 minutes. No concentration of the drug was detected in blood 24 hours after the administration.
Two permanent T-cell leukemia lines designated KH-1 and KH-2 were established from the peripheral blood of a 9-year-old boy with acute lymphoblastic leukemia and a 47-year-old man with adult T-cell leukemia (ATL). No T-cell growth factor was used. KH-1 cells grew as single cells and KH-2 cells formed clusters in suspension culture. Erosette formation, the absence of immunoglobulin determinants and Epstein-Barr-virus-associated nuclear antigen, and the presence of T-cell antigens revealed by monoclonal antibodies were characteristics of these cell lines as in other established T-cell leukemia lines. Chromosome analysis at the beginning revealed mosaic presence of cells with 46, XY, t(8q+; 15q-) and 46, XY which was later completely replaced by the latter karyotype in KH-1, and abnormal karyotype, 47, XY, +3, t (8q-; 10p+) was maintained throughout the period of in vitro passage in KH-2. The donor patient of KH-2 formerly lived in the south-western part of Japan where ATL is considered endemic and numerous type-C virus particles were detected electron microscopically, in KH-2 cell pellets.
To establish a convenient method for decontaminating bioclean rooms, the effect of ozone at 80 mg/m3 for 72 h was compared with formaldehyde vaporization at an initial concentration of 150 mg/m3 with a gradual decrease to 20 mg/m3 during 72 h. Ozone was found to be inferior to formaldehyde in activity. When the bioclean room was decontaminated twice with ozone, the mean colony count per 10 cm2 was decreased to about the same level as when formaldehyde was used. Ozone had a strong caustic effect upon rubber materials. Despite these disadvantages, ozone decontamination was demonstrated to be superior to formaldehyde vaporization because of convenience, insignificant inhalation of the disinfectant by the hospital staff, and very rapid expulsion of the gas after ventilation. Because the disadvantages of ozone can be easily controlled, this study suggests that ozone decontamination is a promising method for maintaining bioclean rooms.
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Recent progress in the treatment of acute leukemia is so rapid and wide-ranged that it is difficult to detail the progress. Therefore we limit this paper focusing following items: 1) FAB classification and therapeutic response; 2) 5000 leukocyte differential and survival; 3) bone marrow transplantation; and 4) over all survival and 5-year survival. 1) FAB classification and therapeutic response: 59 cases of acute non-lymphocytic leukemia were classified according to FAB classification: (M5-16 cases. The differences in the complete remission rate, duration of remission and median survival were not significant among these groups. 2) 5000 leukocyte differential and survival: 86 cases with acute leukemia which achieved complete remission were divided into three groups according to the levels of remaining leukemic cells by 5000 leukocyte differential: 0-1/5000-39 cases, 2-4/5000-24 cases and 5-/5000-23 cases. A close correlation between the leukemic cell level during remission and survival of patients was observed. A marked tendency of longer survival was observed in cases in which leukemic cells decreased during remission and vice versa. 3) Bone marrow transplantation (BMT) therapy: Up to now, 15 patients have been treated and 4 of them are alive now. The longest survival is a case of a 9 year old boy with ALL, who is doing well after BMT for one year and a half. 4) Median survival and 5-year survival: Overall median survival of acute leukemia patients was 7 months (1970-1974) and 12 months (1975-1979). We have experienced 12 patients of 5-year survivors. Out of them, 7 patients are still in remission for more than 6 years. The 5-year survival rate was 0.5% before 1969, and 8.3% after 1970. This indicates a remarkable improvement in the treatment of acute leukemia.
Forty-six cases with hematological malignancies were treated with vindesine sulfate (VDS); a new semisynthetic vinca alkaloid. Six cases with ALL, 5 cases CML in blastic crisis, 3 Hodgkin's disease (HD) and 4 non-Hodgkin's lymphoma (NHL) were treated with VDS alone. Five out of 6 cases ALL, 2 out of 5 CML in blastic crisis were induced into partial remission with VDS alone. All of 3 HD, and 4 NHL were induced in complete remission (CR) or partial remission (PR). Out of 5 cases AML in CR who received VDS as the maintenance therapy in combination with cyclophosphamide, 6-MP and prednisone, one case relapsed during the treatment, but other four cases maintained CR for 4 to 24 months. One case of APL in relapse, which was treated with VDS and 6-MP, reinduced into CR after one month. Out of 16 cases with malignant lymphoma treated by combination chemotherapy including VDS, eleven cases entered in CR or PR. Out of four cases in which the disease became refractory to vincristine (VCR) or vinblastine (VLB) clinically, two achieved PR. VDS was administered intravenously with 3 mg/body/week. When undesirable effect such as leucocytopenia was observed, the dose was reduced to 2-2.5 mg/body/week or 3 mg/body/2 weeks or month. Neurotoxicity (i.e. Paresthesia 21.7%), alopecia (21.7%), leucocytopenia (19.6%), constipation (10.9%) and fever (6.5%) were main side effects of VDS. The neurotoxicity of VDS, however, seemed far less intensive than VCR.
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