The metabolism of Rifampicin after the oral administration to man is the subjects of interest. Biological assay is usually applied for the determination of Rifampicin, but the absolute values reported are considerably different, depending on the method used. The authors recently developed a reliable chemical method to determine serum and urinary Rifampicin, and had an opportunity to investigate the metabolism of the drug in man by using the chemical assay in place of unstable biological assay heretofore in use. The present paper discussed a number of remarkable findings obtained from observation of 13 patientswith pulmonary tuberculosis during continuous administration of Rifampicin, 450mg daily.

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In order to examine change of nucleotides metabolism in surgical stress, urinary excretion of D-β-amino-isobutyric acid (β-AIB) and β-alanine which are metabolites of thymine and uracil, respectively, were determined. Patients with tuberculosis excreted larger amounts of β-AIB and β-alanine. The urinary amounts of these amino acids were decreased 3 days after the surgical operation of lobectomy and then it returned to the original level. This change was in contrast to other surgical operations after which the amino acids increased. This paper clarified the mechanism of the peculiar pattern of urinary excretion of these amino acids of patients with tuberculosis after lobectomy.
Determination of urinary β-AIB and β-alanine was performed by using the method of Yanai and Takao, respectively. Activities of β-AIB: pyruvate and β-alanine: α-ketoglutarate aminotransferase were determined by the methods of Tsujio and Kakimoto et al, respectively. Amounts of D-cycloserine (CS) was determined by absorption at 590 mu of 50% ethanol extraction of paper strip of high voltage paper electropherogram after ninhydrin reaction.

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Tuberactinomycin, TUM, is a collective name for a group of peptide antibiotics among which TUMs A, B, N and O may be distinguished. In 1968 Nagata et al. reported the antituberculous antibiotic tuberactin produced from a strain, B-386, of Streptomyces griseoverticillatus var. tuberacticus, which was later renamed TUM and finally found to be a mixture of two components A and B; the latter identified as viomycin. A mutant of the strain, designated N-130, produced TUMs N and 0.
The present paper describes an attempt designed to compare the in vitro and in vivo activities of these components and also reports cross-resistance studies in vitro.
In vitro observations: The results are recorded in Tables 1 and 2. It may be noted that each of the TUMs inhibited the growth of the H37Rv drug-susceptible strain in a concentration of 4 or 8mcg per ml in Kirchner's semi-liquid medium with 10per cent horse serum, and of 25mcg per ml in Ogawa's egg medium. Cross-resistance studies were' performed utilizing 22 drug-resistant H37Rv strains. The strains resistant to SM, KM, PAS, INH, CS, EB, ETH, and RFP were all sensitive to the TUMs (TUM-A, Me-TUM-A, and TUM-N), whereas the VM and CPM-resistant strains were resistant to the TUMs. On the: other hand, the strains resistant to TUMs were all susceptible to SM, PAS, INH, CS, EB, ETH, and RFP, but not to VM and CPM. The slightly TUM-resistant strains (nos. 22 and 24 in Table 2-b) were sensitive to KM, whereas the highly TUM-resistant strains (nos. 21 and 23) were resistant to KM. In brief, among the strains resistant to TUMs, VM, and CPM complete reciprocal cross-resistance was observed, while incomplete non-reciprocal. cross-resistance was found between the strains resistant to TUMs and KM.

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Clinical effects of dialy and intermittent chemotherapy with rifampicin (RFP) were compared in patients with advanced already treated pulmonary tuberculosis.
The patients were civided into two groups; group A, 43 cases: RFP were administered 450 mg dialy for 6 months, and group B, 31 cases: RFP were administered 600mg three times a week for 6 months. In 2 cases of group A, three other susceptible drugs were combined with RFP, in 3 cases two drugs and in 17 cases one susceptible drug were also combined. In 2 cases of group B, three other susceptible drugs were combined with RFP, in. 3 cases two and in 8 cases one were also combined. In the remaining cases 20 cases in group, A and 18 cases in group B, no susceptible drug was combined (table 1).
The background factors of the cases in group A and group B were as follows: cases older than 40 years of age occupied 81% of group A and 87% of group B, cases with more than 10 years of previous chemotherapy were 40% of group A and 45% of group B, far advanced. cases according to NTRDA classification were 74% of group A and 90% of group B, far advanced mixed type by “Gakken” classification were 28% of group A and 39% of group, B, cases with sclerotic walled cavity were 77% of group A and 94% of group B, bacilli were positive on smear in 79% of group A and 68% of group B (table 2).
The rate of sputum conversion was 5 5.9% after 3 months treatment and 62.8% after 6 months in group A, and 46.7% after 3 months and 46.7% in 6 months in group B (table 3). The percent of the cases whose sputa became negative consecutively at the fourth, fifth and sixth months after administration of RFP without combination of susceptible drugs was 28.6% in far advanced mixed type of group A and 0% in group B, and in slighter cases, other than far advanced mixed type, the rate was 54.2% in group A and 46.1% in group B; among cases treated with combination of other susceptible drugs, the rate was 33.8% in far advanced mixed type of group A and 20.2% of group B, and in slighter cases other than far advanced mixed type, the rate was 82.5% in group A and 71.4% in group B (table 4).
Chest roentgenogram showed improvement in 18% of group A and 18% of group B after 6 months treatment (table 5).
Adverse effects were observed in 18.5% of group A; transient elevation of S-GOT and/or S-GPT in 6 cases, nausea and vomiting in 1 case, heart brun in 1 case, although, the administration of RFP was continued except transient intermission in 1 case. In group B, advers effects were observed in 9.3%; elevation of S-GOT and S-GPT in one case (the administration of RFP was stopped in this case), transient elevation of GPT in one case, and skin eruption and psychological disturbance in one case (the dose of RFP was reduced in this case).
In conclusion, the therapeutic effects of daily treatment with 450mg RFP was slightly more effective than those of intermittent treatment with 600mg RFP three times a week.

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A co-operative study was carried out by 11 national chest hospitals in various places of Japan, using the same technique of screening for ‘atypical’ mycobacteria (mycobacteria other than tubercle bacilli). The screening by ‘salicylate medium’ (Tsukamura, M.: Amer. Rev. Resp. Dis., 86: 81-83, 1962) or ‘p-nitrobenzpate medium’ (Tsukamura, M.& Tsukamura, S.: Tubercle, 45: 64-65, 1964) was made on mycobacterial cultures isolated from all patients hospitalized in the months, June, September and December 1971 and March 1972.
All strains obtained by the screening were identified according to the schedule described previously (Tsukamura, M.: Tubercle, 48: 311-338, 1967; Tubercle, 50: 51-60, 1969). The following useful tests were also used: Tween hydrolysis (Wayne, L. G., Doubke, J. R.& Russell, R. L.: Amer. Rev. Resp. Dis., 90: 588-597, 1964); ethambutol resistance for differentiating pathogenic and non-pathogenic ones of Group II and Group III (Tsukamura, M.: Kekkaku, 45: 237-240, 1970); alpha and beta-esterases (Käppler, W.: Beitr. Kiln. Tuberk., 130: 1-4, 1965); tolerance to nitrite (Tsukamura, M.& Tsukamura, S.: Amer. Rev. Resp. Dis., 98: 505-506, 1968).

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A case, who developed acute thrombocytopenia with gingival bleeding following an intermittent administration of high dose of rifampicin is reported.
The patient, a 53-year-old Japanese woman, was diagnosed in 1940 as pulmonary tuberculosis. Since 1956 she had received therapy with various combinations of streptomycin, sodium paraaminosalicylate, isoniazid, kanamycin, viomycin, ethionamide and ethambutol without any toxicity and hypersensitivity. Acid fast bacilli had been found on direct examination of her sputum, and cultures for mycobacterium tuberculosis had been positive.
From April 1971 the regimen was changed to ethambutol 1.0g plus isoniazid 500mg daily plus kanamycin 2.0g plus rifampicin 900mg twice weekly. In August 1971, after four months of the therapy, she complained of gingival bleeding and spots of skin.
The numerous small petechiae were generally seen on skin. There were no hepato splenomegaly and no other relevant physical findings. The platelets were 60, 000/cu. mm, and total white cell count 6, 100/cu. mm, and red cell morphology was normal. Rifampicin and other drugs were discontinued. Two days after the discontinuation of the drugs, the purpuric eruptions faded and after two weeks the platelet count returned to normal.
After four weeks, 450mg of rifampicin was readministered, and three hours later the platelet count dropped from 260, 000/cu. mm to 4, 100/cu. mm and at 27 hours later to 1, 800/cu. mm. At fourth day, the platelet count began to rise, and reached to 200, 000/cu. mm at five days after the readministration. After three months she became well with platelets of 360, 000/cu. mm.

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