(Vol.73 No.11 November 1998) <1> Kekkaku Vol.73,No.11:611-617,1998 CLINICAL REVIEW OF 74 CASES WITH MILIARY TUBERCULOSIS Hideaki NAGAI*, Atsuyuki KURASHIMA, Shinobu AKAGAWA, Atsuhisa TAMURA, Naohiro NAGAYAMA, Yoshiko KAWABE, Harumi SHISHIDO, Kazuko MACHIDA, Koji SATO, Hideki YOTSUMOTO, Masashi MORI, Akira HEBISAWA Seventy-four cases of miliary tuberculosis were studied retrospectively. The mean age of the patients was 45.3 years. Twenty-two patients suffered from another underlying diseases. Six were infected with human immunodeficiency virus. Twelve had been terated with corticosteroids. Fever was present in 97.3 per cent of patients. Elevation of serum alkaline phosphatase was found in 67.6 per cent of cases. The skin reaction to tuberculin was positive in 61.2 per cent. Nodular shadows were found in the chest X-ray in 98.6 per cent of cases. The nodules were smaller than 2mm in diameter in 52.7 per cent of cases. Other findings were enlargement of mediastinal lymph node (17.6%), cavities (23.0%), pleural effusion (27.0%), and consolidation (35.1%). Sputum cultures and urine cultures were positive for Mycobacterium tuberculosis in 76.8 per cent and 58.6 per cent of cases respectively. The diagnosis was confirmed by histopathological findings in some cases. The rate of positive biopsies was 61.5 per cent by bone marrow aspiration, 83.3 per cent by lymph node biopsy, 100 per cent by liver and lung biopsy. Antituberculosis therapy was successful in most of the patients. Seven patients died of miliary tuberculosis, 4 of them had adult respiratory distress syndrome. Key words: Miliary tuberculosis, Steroids, Alkaline phosphatase, Bone marrow aspiration, Adult respiratory distress syndrome(ARDS), Human immunodeficiency virus *From the Department of Respiratory Diseases, National Tokyo Chest Hospital, 3-3-1, Takeoka, Kiyose-shi, Tokyo 204-8585 Japan. (Received 7 May 1998/Accepted 1 Jul. 1998) <2> Kekkaku Vol.73,No.11:619-624,1998 LUNG CANCER IN PATIENTS WITH SEQUELAE OF TUBERCULOSIS Atsuhisa TAMURA*, Hideaki NAGAI, Yuzo SAGARA, Yoshiko KAWABE, Shinobu AKAGAWA, Naohiro NAGAYAMA, Kazuko MACHIDA, Atsuyuki KURASHIMA, Koji SATO, Hideki YOTSUMOTO, Masashi MORI and Akira HEBISAWA To clarify features of lung cancer in patients with tuberculosis sequelae, we analyzed data on 15 cases (5.1%) who were diagnosed with lung cancer before death among 294 deceased cases with tuberculosis sequelae at our hospital. There were 12 men and 3 women, with a mean age of 64 years. Most of the 15 patients had pulmonary dysfunction, and 4 had received home oxygen therapy. All 12 men had a history of smoking, and 10 of them had squamous cell carcinoma of the lung. There was no definite correlation between the locations of the tuberculosis lesion and those of lung cancer lesion on chest X-rays. Twelve patients had thoracoplasty for tuberculosis, and in 6 of these patients the lung cancer occurred in the same lung. Lung cancer was apt ot be diagnosed in an advanced stage. However, in patients who received home oxygen therapy, diagnosis had been made at an early stage because ot the frequent chest X-ray follow-up. We conclude that lung cancer is an important complication in patients with tuberculosis sequelae, and early diagnosis of lung cancer by careful follow-up is essential in the care of cases with tuberculosis sequelae who have poor pulmonary function and/or systemic conditions. Key words: Sequelae of tuberculosis, Lung cancer, Thoracoplasty, Squamous cell carcinoma, Radiographic findings *From the Department of Respiratory Diseases, Tokyo National Chest Hospital, 3-1-1, Takeoka, Kiyose, Tokyo 204-8585 Japan. (Received 12 May 1998/Accepted 6 Jul. 1998) <3> Kekkaku Vol.73,No.11:625-631,1998 INVESTIGATIONS INTO THE SIGNIFICANCE OF ROUTINE HEALTH EXAMINATIONS FOR TUBERCULOSIS IN THACHERS BASED ON THE ANALYSIS OF RESULTS OF EXTRAORDINARY HEALTH EXAMINATIONS Masahiko YAMAMOTO* School teachers are regarded as one of the danger groups in contracting tuberculosis infection and are subjected to strict tuberculosis controls, since when they develop tuberculosis, many school children are exposed to infection to the disease. However, the recent decrease in the incidence of tuberculosis in Japan has led to disputes concerning the significance of routine mass health examinations for tuberculosis. In this study, the significance of routine health examinations for tuberculosis in teachers was investigated by analysis of the results of extraordinary health examinations carried out for tuberculosis in teachers as the index cases. A total of 496 extraordinary health examinations were carried out by Nagoya City from 1975 to 1986 and by Aichi Prefecture from 1980 to 1995. In 49 instances of these examinations, teachers were regarded as index cases, which included 25 teachers of public primary, middle or high schools and 14 teachers of private schools, including private instructors for piano, panting or calligraphy, and teachers for supplementary education. The results of these examinations in both groups were compared, regarding the routes of notification, the disease status of the index cases, and the frequency and the scale of the infections of tuberculosis observed among contacts with the index cases. gGroup infections of tuberculosis" was defined as instances the infection in which 20 or more cases were infected by the index case, gsmall scale group infection" as 5-19 infected cases, and gcases with infection" as 1-4 infected cases. The result obtained were as follows. 1. The response rates to routine health examinations were 99.9% in the teachers of public primary, middle or high schools, and about 20`30% in the teachers of private schools. 2. The proportion ot the cases notefied by routine examinations were 68.0% in the former group and 21.4% in the latter group. The cases notefied bvefore the onset of the symptoms in the former group was significantly more frequent than in the latter group. 3. In the former group, no far advanced cases were identified, whereas 2 (14.3%) far advanced cases were identified in the latter group. The cases with amount of tubercle bacilli in sputum exceed 3 on the Gaffky scale were 32.0% in the former group and 61.5% in the latter group. 4. One (4.0%) case if the ggroup infections of tuberculosis" was observed in the former group, and 2 (14.3%) cases in the latter group. gSmall scale group infection" was obserted in 4.0% of the former group and in 21.4% of the latter group, and gcases with infection" in 8.0% of the former group and in 35.7% of the latter group. The frequency and the scale of the infections of tuberculosis observed among contacts with the index cases was significantly smaller in the former group than in the latter group. In conclusion, routine health examinations for tuberculosis for teacheres seems valuble for the early diagnosis of tuberculosis cases and for the prevension of the infection of tuberculosis in schools. Key words: Tuberculosis in teachers, Routin health examination, Mass health examination, Chest photofluorography, Extraordinary health examination, Group infection of tuberculosis *From the Nagoya Medical Examination Center, Postal Life Insurance Welfare Corporation, 1-21 Shumoku-cho, Higashi-ku, Nagoya 461-0014 Japan. (Received 18 Mar. 1998/Accepted 30 Jul. 1998) <4> Kekkaku Vol.73,No.11:633-637,1998 TWO CASES OF PULMONARY DISEASE DUE TO MYCOBACTERIUM SZULGAI Tadakatsu TSUJI*, Hiroyuki MATSUMOTO, Kyoko NAKANISHI Akinori TAKEDA, Toshiaki FUJIKANE and Tetsuo SHIMIZU This paper described with two patients with pulmonary disease due to Mycobacterium szulgai. The first patient was a 67-year-old man who consulted a doctor at the outpatient clinic of the Internal Medicine of our hospital, complaining with hemosputum. A chest X-ray showed an infiltrative shadow in the right upper lobe. A smear test of the sputum was negative but a culture was positive for mycobacteria. Second patient was a 37-year -old man who was admitted to our hospital, complaining with cough and fever. A chest X-ray showed an infiltrative shadow with cavity in the right upper lobe. A smear test was positive and culture was positive for mycobacteria. Cultured isolates of the two cases were indentified as M.szulgai. These two patients were treated with isoniazid, rifampicin and ethambutol daily. Their clinical symptoms improved and their sputum smears and cultures converted to negative for mycobacteria. Key words: Nontuberculous mycobacteriosis, Mycobacterium szulgai, Chest X-ray and CT findings, Chemotherapy, Clinical features *From the Division of Internal Medicine, National Dohoku Hospital, Hanasaki-cho 7, Asahikawa, Hokkaido 070-0901 Japan. (Received 14 Apr. 1998/Accepted 1 Jul. 1998) <5> Kekkaku Vol.73,No.11:639-644,1998 The 73rd Annual Meeting Special Lecture MECHANISMS OF INDUCTION AND EXPRESSION OF ANTI-TUBERCULOUS IMMUNITY Masao MITSUYAMA* The induction of anti-tuburculous immunity highly depends on the cytokines produced endogenously at the initial stage of immunization. Among several cytokines, IFN- appeares to be the most important to generate antigen-specific Th1 type of protective T cells in mice. IL-12 and IL-18, which are produced by macrophages on response to virulent mycobacteria, are responsible for stimulating NK cells to produce IFN-. Once antigen-specific Th1 cells are generated, Th1-dependent macrophage activation was effective in the elimination of infected bacteria through enhanced production of reactive oxygen intermediates and reactive nitrogen intermediates. In Listeria monocytogenes, one of the intracellular bacteria, listeriolysin O (LLO) appeared to be responsible for the induction of endogenous IFN- from NK cells. The possible mechanisms operating in the induction and expression of anti-tuberculous immunity are discussed with special reference to cytokine responses. An application of LLO to the induction of protective immunity is also discussed. Key words:Anti-tuberculous immunity, Cytokine, Gamma interferon, Macrophage, Th1 cells *From the Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshida-Konoecho, Kyoto 606-8501 Japan. (Received 24 Sep. 1998) <6> Kekkaku Vol.73,No.11:645-647,1998 The 73rd Annual Meeting Symposium J. MULTIDRUG-RESISTANT TUBERCULOSIS Chaipersons:Hajime SAITO*, Ryoichi AMITANI** Symposium Topics and Presenters: 1. Drug susceptibility testing and its standardization:Chiyoji ABE(Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association) 2. Mechanisms of drug-resistance in Mycobacterium tuberculosis-Genetic mechanisms of drug-resistance-:Hideaki OHNO (The Second Department of Internal Medicine, Nagasaki Universtiy School of Medicine, and Hokusho Chuou Hospital), et al. 3. Epidemiology of drug-resistant tuberculosis in Japan:Takashi YOSHIYAMA(Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association) 4. Treatment and prognosis of multidrug-resistant tuberculosis:Mitsumasa OGAWARA, et al. (Department of Internal Medicine, National Kinki-Central Hospital for Chest Diseases) 5. Human immunodeficiency virus infection and multidrug-resistant tuberculosis: Akira FUJITA (Tokyo Metropolitan Fuchu Hospital) Additional Comment:Primary multidrug-resistant tuberculosis-diagnosis and Treatment: Kazunari TSUYUGUCHI (Department of Infection and Inflammation, Graduate School of Medicine, and Department of Internal Medicine, University Hospital, Kyoto University. Multidrug-resistant tuberculosis (MDR-TB) is defined as one that is resistant to both isoniazid and rifampicin regardless of its resistance to any other antituberculosis drugs. According to gStudy on the incidence of drug resistance for new admissions" reported by TB Sanatorium Council in 1992 in Japan, no increase of incidence was observed in either the first teratment or re-treatment as compared with former reports. However, U.S.A. study indicates a significant increase of MDR-TB, which is supposed to have been caused by a primary drug resistance prevailed in an infected area, or an acquired (secondary) drug resistance due to incomplete and/or faulty treatment for active TB. Many incidences were also reported for mass nosocomial infection of MDR-TB with HIV patients. In spite of these serious issues in U.S.A., MDR-TB has not yet been a major concern in Japan, while Japan should work out countermeasures in advance with careful observation of its tend. One of the causes of mass nosocomial infection of MDR-TB observed in U.S.A. is reported due to a delayed teratment after long procedures of TB identificaiton and susceptibility tests followed specimen sampling. Rapid tests of identification and susceptibility for TB, MDR-TB in particular, are long expected. The introduction of recent molecular genetics technology will help to develop new rapid tests. While a relationship between drug resistance and TB gene is recently known to certain extent, total mechanism of TB resistance cannot be fully explained with only certain gene identified in the connection with drugs. Early treatment is critical for MDR-TB with HIV patient, as their prognosis is far worse than MDR-TB with non-HIV. Aside from HIV infection, very limited drugs are available for the treatment of MDR-TB. Drugs should be carefully selected based on the resistance patterns of each strain as well as its side effects anticipated. Key words:Multidrug-resistant tuberculosis, Drug susceptibility test, Molecular genetics, Human immunodeficiency virus infection *From the Hiroshima Environment and Health Association, 9-1 Hirosekita-machi, Naka-ku, Hiroshima 730-8631 Japan. **From the Department of Infection and Inflammation, Graduate School of Medicine, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8397 Japan (Received 11 Sep. 1998) <7> Kekkaku Vol.73,No.11:649-655,1998 The 73rd Annual Meeting Symposium J. MULTIDRUG-RESISTANT TUBERCULOSIS 1. DRUG SUSCEPTIBILITY TESTING AND ITS STANDARDIZATION Chiyoji ABE* Drug susceptibility testing is one of the most difficult procedures to standardize in mycobacteriology laboratories, International standardization of the test is needed for comparative evaluation of controlled chemotherapeutic trials, for epidemiological surveys on the prevalence of drug resistance, and for guidance in the treatment of tuberculosis patients. In 1996, a new procedure for durg susceptibility testing was proposed by an ad hoc committee of the Japanese Society for Tuberculosis. The proposal is for a test with the proportion method using an Ogawa egg medium similar to those recommended by the WHO. Resistance is expressed as the percentage of colonies that grow on critical concen- trations of the drugs, i.e. 0.2g/ml for isoniazid, 40g/ml for rifampicin, 10g/ml for streptomycin and 2.5g/ml for ethambutol. Strains of tubercle bacilli which are grown on drug-containing media represents more than 1% of the number of colonies that develop on drug-free media are considered to be clinically resistant to that agent. The results are recorded as susceptible (S) or resistant (R) on the laboratory forms. The proportion method using agar-and liquid-based media is used worldwide. In the near future a test with agar-or liquid-based media will be disscussed for standardization of the test in Japan, as described by the National Committee for Clinical Laboratory Standards of the United States. Key words:Drug Susceptibility Testing, Mycobacterium tuberculosis, Proportion Method, Ogawa Egg Medium *From the Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, 3-1-24, Matsuyama, Kiyose-shi, Tokyo 204-8533 Japan. (Received 11 Sep. 1998) <8> Kekkaku Vol.73,No.11:657-663,1998 The 73rd Annual Meeting Symposium J. MULTIDRUG-RESISTANT TUBERCULOSIS 2. MECHANISMS OF DRUG-RESISTANCE IN MYCOBACTERIUM TUBERCULOSIS -Genetic Mechanisms of Drug - Resistance - Hideaki OHNO, Hironobu KOGA, and Shigeru KOHNO* Multidrug-resistant Mycobacterium tuberculosis infection is now world wide health problem. However, according to the recent advances of molecular biological technics, some of the genetic mechanisms of drug-resistance of M.tuberculosis has been uncovered. Gener- ally, drug-resistance of M.tuberculosis was caused by point mutations in chromosomal gene. In isoniazid (INH) resistant M.tuberculosis, mutations and genetic deletions in catalase-peroxidase gene (katG), inhA gene, or alkyl hydroperoxide reductase gene were reported. We also found that about 15% of INH-resistant M.tuberculosis isolates lacked katG gene, and these isolates showed highly resistance to INH with MIC 64 g/ml. On the other hand, mutations and other genetic alterations in RNA polymerase subunit gene (rpoB) were the major mechanisms of resistance to rifampicin (RFP) with high frequencies of 90% or more. Our evaluation of the relationship between RFP susceptibility and genetic alteration in rpoB gene also showed that 95% of RFP-resistant M.tuberculosis isolates involved genetic alterations in 69 bp core region of rpoB gene. Moreover, these genetic alterations in rpoB gene were suspected as the resistant mechanism to other rifamycin antituberculosis drugs, such as rifabutin and KRM-1648. In addition, it was reported that point mutations in 16S rRNA gene (rrs) and ribosomal protein S12 gene (rpsL) induced M.tuberculosis as streptomycin (SM) resistant phenotype. We analyzed genetic alterations in rpsL gene of clinically isolates of M.tuberculosis, about 60% of SM resistant isolates were shown point mutation in this gene ant they were all high SM -resistant with MIC256g/ml. Furthermore, nicotinamidase (pncA) gene, DNA gyrase A subunit (gyrA) gene, and embB gene were reported as the responsible gene to pyrazinamide-, quinolone- and ehambutol-resistance, respectively. Although all mecha- nisms of drug-resistance were still unclear, these informations are very useful and helpful for development of rapid diagnosis system of drug-resistant M.tuberculosis. Key words:Drug-resistant Mycobacterium tuberculosis, katG gene, rpoB gene, rpsL gene, Point mutation. *From the Second Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto 1-7-1, Nagasaki 852-8501 Japan. (Received 11 Sep. 1998) <9> Kekkaku Vol.73,No.11:665-672,1998 The 73rd Annual Meeting Symposium J. MULTIDRUG-RESISTANT TUBERCULOSIS 3. EPIDEMIOLOGY OF DRUG-RESISTANT TUBERCULOSIS IN JAPAN Takashi YOSHIYAMA* In Japan, the frequency of drug-resistant tuberculosis has been investigated every 5 years since 1950s and increase of initial and acquired drug resistance has not been observed. However, the mathematical model analyse of time trend of prevalence of drug- resistant tuberculosis and frequency of initial drug resistance in Korea shows that there is little difference of infectivity and/or proportion of clinical breakdown between suscep- tible bacilli and resistant ones. The prognosis of isoniazid (INH) and rifampicin (RFP) resistant tuberculosis cases in Fukujuji Hospital was investigated. 367 cases including 50 initial drug resistant cases were analyzed with life table analysis. 50% of all cases and 70% of initial drug resistant cases became negative, 13% of all cases and 4% of initial drug resistant cases remained as positive, 37% of all cases and 27% of new cases died. Among cases who did not convert negative within one year, 41% of all cases and 34% of initial drug resistant cases died. The prognosis of INH and RFP resistant tuberculosis cases were still not satisfactory. Key words:Tuberculosis, Drug resistance, Epidemiology Prognosis *From the Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, 3-1-24, Matsuyama, Kiyose-shi, Tokyo 204-8533 Japan. (Received 11 Sep. 1998) <10> Kekkaku Vol.73,No.11:673-677,1998 The 73rd Annual Meeting Symposium J. MULTIDRUG-RESISTANT TUBERCULOSIS 4. TREATMENT AND PROGNOSIS OF MULTIDRUG-RESISTANT TUBERCULOSIS Mitsumasa OGAWARA* and Mitsunori SAKATANI We studied the clinical characteristics, treatment and prognosis of multidrug-resistant pulmonary tuberculosis patients retrospectively. In this study, multidrug-resistant is defined as both resistant to 0.1g/ml of INH and 50g/ml of RFP at least. From 1990 to 1997, out of 1841 culture positive pulmonary tubeculosis patients, 76 patients (4%) proved to be multidrug-resistant (53 males, 23 females, age 18-84, 40 originally treated cases and 36 relapse cases). Most of cases revealed resistance to other drugs in addition to INH and RFP. The combination of anti-tuberculous drugs were complicated and changed repeatedly. The incidences of administration of drugs were as follows;TH 62%, EB 58%, PZA 58%, KM 33%, PAS 33%, SM 29%, CS 20%, EVM 14%, CPM 3%. New quinolones, for example OFLX/LVFX, CPFX and SPFX, were also used frequently (62%). Eight percent of patients were operated. Bacteriologically effective drugs that meant culture negative were TH (14%), PZA (12%), KM (12%), EB (12%), SM (5%), new quinolones (16%). 67% of originally treated cases and 43% of relapse cases became culture negative. Many cases were treated for a long period. 19% of originally treated cases and 33% of relapse cases were treated more than three years. 11% of patients were died of tuberculosis. Major prognostic factors were diabetes mellitus (17%), malignancies (10%), non-adherence (9%) and other complications. Because of no absolutely effective treatment, we have to choose a treatment according to each patient. Development of new treatment is crucial. Key words:Multidrug-resistant tuberculosis, Pulmonary tuberculosis, Treatment, Chemotherapy, Prognosis *From the Department of Internal Medicine, National Kinki-Central Hospital for Chest Diseases, Nagasone-cho 1180, Sakai-shi, Osaka 591-8555 Japan. (Received 11 Sep. 1998) <11> Kekkaku Vol.73,No.11:673-677,1998 The 73rd Annual Meeting Symposium J. MULTIDRUG-RESISTANT TUBERCULOSIS 5. HUMAN IMMUNODEFICIENCY VIRUS INFECTION AND MULTIDRUG-RESISTANT TUBERCULOSIS Akira FUJITA* Outbreaks of multidrug-resistant tuberculosis (MDR-TB) among human immunodeficiency virus (HIV)-infected persons reported in the United States were very serious and the risks were increased by the delay of diagnosis, rapid progression from infection to active disease, inadequate therapy and poor tuberculosis (TB) control. Prevalence of drug -resistant TB among HIV-infected patients in Japan was studied. The results of drug susceptibility were collected through the nationwide working group for a survey of HIV-in- facted TB. Data of susceptibility for 39 cases were obtained. The isolates of two cases were resistant to isoniazid and rifampicin (including clinical failure of response), al- though no outbreak of MDR-TB was found in Japan. Case study of a patient who developed MDR-TB revealed that drug resistance might be selected by insufficient anti-TB therapy. The rate of resistance to any of the anti-TB drugs in HIV-infected patients seemed to be high, although strictly evaluation was difficult due to no standardization for drug susceptibility testing. Of 9 cases with resistance to any of the anti-TB drugs, 8 had extrapulmonary TB including 5 cases of disseminated TB. In contrast thirteen of 30 cases without drug resistance had extrapulmonary TB. Since it has been reported that HIV infection is related to increased rates of drug resistance of TB bacilli, treatment with four-drug regimen should be started and sufficient courses fo therapy are needed in HIV-infected TB patients. Key words:Multidrug-resistant tuberculosis(MDR-TB), Human immunodeficiency virus (HIV) Infection, Acquired immunodeficiency syndrome(AIDS), Extrapulmonary tuberculosis *From the Tokyo Metropolitan Fuchu Hosoital, 2-9-2, Musashidai, Fuchu-shi, Tokyo 183-8524 Japan. (Received 11 Sep. 1998) <12> Kekkaku Vol.73,No.11:687-690,1998 The 73rd Annual Meeting Symposium J. MULTIDRUG-RESISTANT TUBERCULOSIS Additional Comment:PRIMARY MULTIDRUG-RESISTANT TUBERCULOSIS-DIAGNOSIS AND TREATMENT Kazunari TSUYUGUCHI* Primary drug resistance is defined as the presence of resistant strains of Mycobancreium tuberculosis in a patient with no history of prior anti-tuberculosis chemotherapy. In Japan, a recent study shows that the prevalence of primary resistance has been stable for two decades and that primary multidrug-resistant tuberculosis (MDR-TB) is rare, which suggests the effectveness of tuberculosis control. We presented four cases of primary MDR-TB that we had experienced from 1984 to 1997, and discussed an issue about diagnosis and teatment of primary MDR-TB. Of the four patients, two young men received surgical resection, which has resulted in a favorable outcome. Of the other two patients, one responded to long-term chemotherapy with ethambutol, ofloxacin and enviomycin. There have been no recurrence so far in the three cases. The rest case died due to progression of tuberculosis. Two of the four patients had been in contact with relatives who had died of MDR-TB. In conclusion, all the tuberculosis patients should be suspected to be primary MDR-TB when they had a history of a contact with a tuberculosis patient in whom chemotherapy had not been successful, and once patients are diagnosed as MDR-TB, surgical intervention should be considered as an adjunctive treatment. To prevent the emergence of primary MDR-TB, it is important to treat MDR-TB patients appropriately and to implement the infection control program. Key words:Multidrug-resistant tuberculosis, Primary resistance, Surgical treatment *From the Department of Infection and Inflammation, Graduate School of Medicine, and Department of Internal Medicine, University Hospital, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8397 Japan. (Received 11 Sep. 1998)