Bactericidal activity of INH and SM to Mycobacterium tuberculosis H37Rv after exposure to PAS were evaluated in vitro by means of Silicone-Coated Slide Culture Method (SSC).
According to the results obtained, it is shown that bactericidal activity of IN H after exposure to PAS for a week, is lowered only in the series in which the culture media containing serial dilution of INH are not replaced, and it is not lowered in the series in which the culture media containing INH are replaced freshly once a week.
As for SM, the diminishing trend of bactericidal activity is not observed in every series of the experiment.

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As one of the big problems of antituberculous chemotherapy for the chronic pulmonary tuberculosis, “microbial persistence”, a capacity of the drug-susceptible microorganisms which are able to survive against the activity of the drug in vivo, has been pointed out. This phenomenon indicates a limitation in tuberculosis chemotherapy other than the drug resistance. In this report, an intensified antituberculous regimen were applied in vitro upon the resting cells of streptomycin-dependent (18-b) strain, isolated from the human origin, under streptomycinstarved condition. By using silicone-coated slide culture method, kanamycin, isoniazid and ethambutol were used singly or in combination upon the resting cells. It was obtained that the drugs were slightly effective against the resting cells, but the effecte was less than that against the growing cells.
This experiment suggests that tubercle bacilli in the resting state cannot survive half a year. If it is true, tubercle bacilli brought in to the resting stage might die in a relatively short period.

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It was previously reported that the treatment for newly found pulmonary tuberculous patients with SM⋅INH⋅EB was clinically more effective than SM⋅INH⋅PAS regimen in respect of the negative conversion rate of tubercle bacilli in sputum and roentgenological improvement. To confirm these findings, the therapeutic effect of various regimens including SM⋅PAS⋅INH and EB were compared in experimental tuberculosis of mice.
The results obtained were as follows:
1) Albino dd/y male mice about 20 g b ody weight were infected intravenously with H₃₇Rv (3.8 × 10⁵/ml) strain. On the fourth day of infection, the mice were divided into the following 8 groups; SM⋅EB⋅INH⋅EB⋅INH, SM⋅PAS⋅INH⋅PAS⋅INH, INH, EB, PAS, and untreated control. SM (20 mg/kg) was given intramuscularly twice a week, and PAS (200 mg/kg), INH (4 mg/kg) and EB (30 mg/kg) were given orally once a day. The treatment was continued for 2 weeks in the half of these groups and for 3 weeks in the remaining. After two weeks treatment, the therapeutic effects were evaluated by comparing the viable unit of tubercle bacilli in the lungs and spleen of the mice in each group. The viable unit of bacilli among groups treated for 2 weeks was less in SM⋅EB⋅INH and EB⋅INH group than in SM⋅PAS⋅INH and PAS⋅INH groups. Same result was observed in the groups treated for three weeks.
2) Pathological investigations were simultaneously performed on the specimens taken from the lungs. Findings were divided into the following 3 categories; (+), (-), and (±): (+)represents the peribronchial monocytes infiltration, grouping of epitheloid cells and the lymphocytes infiltration in every parts of the lung, (-) indicates normal finding, and (±)indicates the one between (+) and (-). Among groups treated with PAS and untreated control, many tuberculous lesions were found in the lungs after two and three weeks treatment and the finding was classified as (+). On the other hand, most of mice were classified as (-) or (±) among the groups treated with SM⋅EB⋅INH, SM⋅PAS⋅INH, EB⋅INH, PAS⋅INH, EB alone, and INH alone.
3) Albino dd/y male mice were infected intravenously with Kurono (6.6×10⁵/ml) strain and treated for ten days with the same combination of drugs as described above. Survival time was observed in these 9 groups. The antituberculous agents were administered as follows; SM (20 mg/kg) intramuscularly twice weekly, INH (0.05 mg/kg), PAS (200 mg/kg )and EB (30 mg/kg) orally once daily.
All animals of the SM treated and control groups died soon after the cessation of treatment, and a similar but slightly better result was seen in PAS treated group. INH group survived for a comparatively longer period in spite of minimal dose of INH. Combined and single therapy of SM⋅EB⋅INH, EB⋅INH and EB was found to be more effective than that of SM⋅PAS⋅INH and PAS⋅INH. The dose of EB evaluated on body weight base was higher than that of PA S, and it might be one of the reasons for better results with EB.
In summary, it may be concluded that EB is more valua ble than PAS when it is combined with INH.

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In Japan, tuberculosis control program is conducted according to the tuberculosis control law. All tuberculosis patients are registered and supervised at the health center.
The following indices used for the evaluation of tuberculosis control w e re made by combining the epidemiological figures such as mortality rate, incidence rate, prevalence and so on.
Rate of infectious (in this article infectious means cavitary and or bacilli positive)
cases among newly registered cases
Rate of infectious cases among reg istered active cases
Average duration of activity
Average duration of i n f e ctivity
Average duration of r e g istration after inactivation
Ratio of mortality to prevalence of infe c t i o us pulmonary tbc.
Ratio of mortality to incidence rate
Distribution pattern of these indices by prefecture fitted to logarithmic normal distribution in the majority of cases.
Various factors which might influence these indices were examined with special reference to their background factors.

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A study was made to review the results of surgical treatments for pulmonary tuberculosis with special reference to the factors which might influence the results among aged patients. The results were evaluated by the successful rate, sputum negative rate, death rate and incidence of postoperative complications. Patients who were older than 60 years, 266 in number, were subjected to the study, and 4, 499 cases who were younger than 30 years were used as a control. They were selected from 14, 971 operated cases excluding cases with bilateral operation and died cases whose causes unrelated to the operation or tuberculosis worsening. They had undergone the operation during the 6 years, period from 1963 to 1968 in 62 institutions affiliated with the Tuberculosis Research Committee (RYOKEN) and had been observed for at least 6months postoperatively.

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Tuberculosis Research Committee (Ryoken) investigated comparatively the therapeutic effects of three regimens, i. e., standard triple treatment with SM⋅INH⋅PAS (EB₀ group), standard triple treatment plus EB twice weekly (EB₂ group) and standard triple treatment plus EB daily (EB₇ group), in order to intensify the initial treatment for pulmonary tuberculosis.
The cases with positive tubercle bacilli and cavities were subjected to this study and were allocated at random for three regimens.
The total number of the c a ses was 272 at the beginning of the treatment, but 48 cases were excluded from the analysis because of the primary drug resistance, etc. Finally, 74cases of EB₀ group, 74 cases of EB₂ group and 76 cases of EB₇ group were analyzed.
SM was injected 1 g a day twice weekly, INH was given O.4 g daily in two divided doses, PAS was administered 10 g daily in three divided doses, and EB was given 750 mg daily or twice weekly at the same day when SM was injected.
The background factors of the cases in ea c h group were almost similar, but the cases with abundant bacilli on smear and (_??_) by culture were observed somewhat less frequently in EB₂ group than in the other two groups.
As to the rates of the radiological improvement and the sputum conversion rate, there was no significant difference among three groups. However, the moderate improvement of the fibrocaseous lesions and cavities were recognized sooner in EB₂ and EB₇ groups than in EB₀ group.
The number of cases, in which the regimens were changed because of side effects or ineffectiveness, were 8 cases in EB₀, group, 9 cases in EB₂ group and 5 cases in EB₇ group. The number of cases with positive sputum by smear or culture after 12 month's treatments were 3 in EB₀ group, none in EB₂ group and 1 in EB₇ group. Therefore, the rate of these unsuccesful cases in EB₀, group, EB₂ group and EB₇ group was 16.7%, 13.6% and 8.3%, respectively.
In order to prove the difference in the effectiveness among three regimens, the follow up-studies for longer period might be required.

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Several workers reported the results of tetrazolium salts-such as TTC (Triphenyl tetrazolium chloride), NTC (Neotetrazolium chloride) for earlier detection of mycobacterial growth. Tetrazolium salts, however, was not used widely because of the inhibitory effect for mycobacterial growth.

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