It is well known that nowadays many strains of tubercle bacilli from clinical test materials do not reveal a vigorous growth, since antituberculous chemotherapy is widely employed. However, only fragmentary views have been reported on the growth of such strains.
Since this fact will exert much influence on the results of examination of tubercle bacilli, the authors attempted a study on it, especially from the point of the frequency of such strains. The strains used were those grown on the media of routine sensitivity tests (213 strains by direct method and 355 strains by indirect method). The growth of tubercle bacilli was examined on the drug resistant strains which had grown up on the media containing either streptmycin 10mcg, 100mcg, PAS 1mcg, 10 mcg. or INH 0.1mcg, 1mcg, 5mcg/ml, on the drug sensitive strains which had grown on the control media and on the mixed drug resistant and sensitive strains. The growth was rated as excellent, usual or poor.

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The in Vitro Effect of Antituberculous Agents in Relation to Drug-Exposure Time on Ogawa Glycerol Egg Medium.
Here in Japan, Ogawa glycerol egg medium is now most frequently used for drug-sensitivity test of tubercle bacilli. However, little information has been available concerning the relation between drug exposure time and antibacterial effect on this me dium. This problem is directly concerned with the stability of potency of antituberculous drugs. In other words, if the decisive effect of test drugs is exerted upon the bacilli more rapidly than the potency-decreasing rate of the drugs, there will be little obstacles in the test. If the reverse is the case, however, the test result might be altered more or less. This state of affairs will not be the same depending upon the nature of drug effect (bactericidal or bacteriostatic) and also upon the drug concentration.
The present authors examined the above problem using streptomycin (SM), isoniazid (INH), and PAS as test drugs. Namely, a time-course viabillity test was conducted by liberating the bacilli once inoculated upon drug-contaning Ogawa megium slants and then by reinoculating then upon fresh drug-free media. In this way, the bactericidal effect of the drugs was checked in relation to drug-exposure time. Two different methods were employed for liberation of the bacilli from drug envirorment. One of them was to homogenize the whole medium and dilute it by ten-fold steps so that the drug concentration might be low enough and the bacillary number might be adequate for subsequent colonial counting. The other method was to wash the surface of bacilli-inoculated media with a O.01 % solution of Triton WR-1339, and this washings and the serial ten-fold dilutions were used for viability test.
Fig.1, 2, and Table 1 are the results a ccording to the former technique and Fig.3 and 4 are those according to the latter technique. Despite of the difference in technique, the results showed the same tendency. Namely, SM in the concentration of 4 mcg/ml and INH of 0.1 mcg/ml showed a marked bactericidal effect after only 3 day contact with bacilli inoculated onto Ogawa medium slants. On the other hand, the activity of PAS was proved mostly bacteriostatic.
The observations gave us a suggestion as follows. The relation between drug-exposure time and antibacterial activity, which will be a factor in drugsensitivity test in association with the stability of drug potency, must be taken into our consideration especially concerning the bacteriostatic concentrations of SM and INH or in the case of essentially bacteriostatic drugs such as PAS, but it is not so vital problem concerning the bactericidal concentration of SM and INH.

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Experimental research work was cond ucted to examine the medium-dependent variation of the antibacterial activity of known antituberculous agents, and thereby to see the influence of test medium upon their antituberculous activity. In view of the practical significance of this work in association with clinical drug-resistance test, three kinds of colonycountable culture medium were brought under our examination, which have most frequently been used in routine laboratory work in this country.

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Bacteriological examination was made on all cases, to whom radiography was indicated according to the results of miniature X-ray findings and tuberculin reaction in the tuberculosis mass surveys carried out in Okierabu-island (1961) and Setouchi-town (1962).
The majority of the specimens examined was laryngeal swab and a few cases was examined by sputum. These specimens were kept in an icebox and each specimen was cultured on three slants of 1% Ogawa's egg media after pretreatment with 4% NaOH on the same day. Then, the slants were kept in an incubator at 37°C and observed for 8weeks.
All of the acid-fast bacilli were investigated on their biological characteristics. Drug resistance was tested by the indirect test method on the strains which were identified as human type tubercle bacilli.

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The author made biochemical analys is on the energy metabolism of tuberculous cavity and its surrounding lung tissue as a part of pathophysiological study of tuberculous cavity in order to investigate the process of cavity formation, development and healing. In the present paper, the results of study on resected lung specimens were discussed, and the results of experimental study will be mentioned in the Part II of the article.
Surgically resected lung specimens, 39 in number, were used for the study. Tissue respiration and succinic dehydrogenase activity (SDH activity) of tuberculous cavity, its surrounding lesion and healthy lung tissue were measured by manometric method, and the relation between these biochemical activities and the nature of tuberculous cavity was analyzed. Furthermore, similar analysis was made on pulmonary cancer tissue as a control, and the results were the following.
1) No statistically significant difference was found in the mean value of tissue respiration and SDH activity among the different parts of resected lung specimens with different clinical background factors. Tissue respiration showed a low value.
2) SDH activity increased in a) surrounding and healthy tissue of bigger cavity, b) cavity with thicker wall, c) fresh lesions (infiltrative caseous type lesion) in surrounding tissue, d) cases with more dense peri-cavitary infiltration. The increase of SDH activity was observed not only in cavitary tissue but also in its surrounding and healthy tissue among cases mentioned above, and the facts show the difference of energy metabolism even in healthy tissue of such cases.
3) The increase of S DH activity was more marked a) in monolocular cavity than in multilocular cavity, b) in cavity with more caseous mass than in cleansed cavity, c) in cases with peri-cavitary infiltration than in cases without it. The facts suggest that the energy metabolism of lung tissue shows significant changes even in healthy parts if there is tuberculous changes in the lung, and the grade of changes is different by the morphological changes of tuderculous cavity and its surrounding tissue.
4) No significant difference was found in SDH activity by the course of pulmonary tuberculosis and the duration of chemotherapy. This may be explained by the fact that the majority of the cases in this study was chronic productive type tuberculosis. It is assumed that there may be difference in SDH activity between fresh and old type tuberculosis, and the problem will be investigated in the Part II of this study. Observing by age and sex, SDH activity tended to show a higher value in older age groups (over 50) than in younger age group and in female than in male.
5) In cancer lung, tissue respiration showed low level in healthy tissue as well as in cancer tissue as in the case of tuberculous lung. As to SDH activity, the value was lower in cancer tissue than in tuberculous cavity, and in peri-cavitary and healthy tissue, the value was higher in cancer lung than in tuberculous lung. The fact shows that the difference in energy metabolism exists between cancer and tuberculosis.

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Following the previous reports, radiological aggravation during and after the cessation of ambulatory chemotherapy was investigated on 3, 464 cases treated for longer than 6 months during the period from January 1953 to December 1960. Radiological aggravation was divided into the following 3 types, namely appearance of new foci, appearance of new foci+enlargement, and enlargement. Number of aggravated cases was 119 (3.5 %) during chemotherapy and 352 (10.2 %) after the cessation of chemotherapy. The results were the following:
1. Aggravation during chemotherapy. Among aggravated cases, appearance of new foci and enlargement were nearly equal in number. Regarding the type of aggravated lesions, exudative and infiltrative-caseous type lesions were more frequently found in newly appeared foci than in enlarged foci. The longer the duration of chemotherapy, the higher the rate of improvement of aggravesions. By chemotherapy longer than 18 months ofter aggravation, 84 % of aggravated foci showed marked or moderate improvement.
2. Aggravation after the cessation of chemotherapy. Among aggravated cases, appearance of new foci was found more frequently than enlargement. The type of aggravated lesions was similar to that of aggravated lesions during chemotherapy, but more severe cases were found among aggravated cases after the cessation of chemothrapy, namely few far advanced cavitary cases were found and 14 % of aggravated cases showed extent more than 1/3 of one lung field. By long-term chemotherapy after aggravation, 82 % showed marked or moderate improvement.
3. Relation between aggravation during and after the cessation of chemotherapy. Among original treatment group, no significant difference was found in the rate of aggravation after the cessation of chemotherapy by the presence or absence of aggravation during chemotherapy, but among retreatment group, the rate of aggravation after the cessation of chemotherapy was higher in aggravated cases during chemotherapy than that in not aggravated cases.

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