(Vol.76 No.2 February 2001) <1>Kekkaku Vol.76 No.2:47-52,2001 TWO-STEP TUBERCULIN SKIN TEST IN GENERAL HOSPITAL WORKERS -Comparison with Nursing Home Workers- *Masami NAKAMATA *Department of Respiratory Medicine, Niigata Rinko General Hospital In 1998, the Japanese Society for Tuberculosis recommended two-step tuberculin skin test(TST) for medical workers. As a large majority of the Japanese were BCG vaccinated in their childhood, it is difficult to distinguish true infection from booster effect. In Japan, it is important to record individual baseline tuberculin reactivity by two-step TST. Two-step TST was performed on 126 general hospital workers and 47 nursing home workers, excluding those whose initial TST was strongly positive, according to the recommendation of the Japanese Society for Tuberculosis in 1998 (strongly positive TST in Japan is defined as the reaction with other intensive responses such as double skin erythema, bleb, lymphangitis, etc.). Diameter of erythema of TST among hospital workers v.s. nursing home workers were as follows. In the initial TST:23.2}16.7mm v.s. 14.2}10.3mm (p<0.001), in the second TST:26.3}17.1mm v.s. 16.7}9.9mm (p<0.02), baseline of TST:32.0}18.3mm v.s. 19.4}10.7mm (p<0.001). Booster effect of TST in hospital workers was +9.8}15.1mm, while it was +4.8}7.8mm (not significant) in nursing home workers. Among those 30 years and over, these differences were no found, except diameter of erythema in the initial TST. In our hospital with no beds for TB, in the past 10 years, tuberculosis has not been broken out among our hospital workers, while several patients with pulmonary tuberculosis have been diagnosed every year (6 patients in 1999). Thus, some hospital workers might be exposed to infection with tuberculosis from these patients. On the other hands, no tuberculosis patients had been diagnosed in the nursing home, and young nursing home workers very rarely exposed to infection with tuberculosis in their life, and they are similar to the general population. This study suggested that hospital workers were more frequently exposed to tuberculosis infection than other workers. Key words:Two-step tuberculin test, Booster phenomenon, General hospital workers, Nursing home workers, BCG vaccination, Nosocomial infection of tuberculosis *1-114-1, Momoyama-cho, Niigata-shi, Niigata 950-0051 Japan. (Received 2 Aug. 2000/Accepted 13 Nov. 2000) <2>Kekkaku Vol.76 No.2:53-57,2001 INVASION AND INTRACELLULAR GROWTH OF MYCOBACTERIUM TUBERCULOSIS AND MYCOBACTERIUM AVIUM COMPLEX ADAPTED TO INTRAMACROPHAGIC ENVIRONMENT WITHIN MACROPHAGES AND TYPE U ALVEOLAR EPITHELIAL CELLS Katsumasa SATO, Tatsuya AKAKI, Toshiaki SHIMIZU, Chiaki SANO, Keiko OGASAWARA, and *Haruaki TOMIOKA *Department of Microbiology and Immunology, Shimane Medical University Profiles of the invasion and intracellular growth of M.tuberculosis (MTB) and M. avium complex (MAC), which had been adapted to intramacrophagic environment, within Mono Mac 6 human macrophages (MM6-Ms) and A-549 human type U alveolar epithelial cells (A-549 cells) were studied. In this study, we used the organisms grown in MM6-Ms (intracellularly-adapted:I-type) and those passaged in 7H9 liquid medium (extracellularly-adapted:E-type). First, I-type MTB was less efficient than E-type MTB in invading into MM6-Ms, while I-type MTB invasion into A-549 cells was greater than of E-type MTB. On the other hand, I-type MAC was more efficient than E-type MAC in entering both into MM6-Ms and A-549 cells. Second, the ability of MTB and MAC to replicate within MM6-Ms was increased by intracellular passage of these organisms through MM6-Ms. In contrast, the ability of these organisms to grow within A-549 cells was decreased to some extent by intramacrophagic passage. These findings suggest that growth within Ms changes the efficiency of MTB and MAC in invading and replicating in Ms and type U alveolar epithelial cells. Key words:Invasiveness, Intracellular growth, Mycobacterium tuberculosis, Mycobacterium avium, Macrophages, Type U alveolar epithelial cells *89-1, Enya-cho, Izumo-shi, Shimane 693-8501 Japan. (Received 28 Sep. 2000/Accepted 30 Nov. 2000) <3>Kekkaku Vol.76 No.2:59-69,2001 PROBLEMS AND THEIR TRANSITION OF LONG-TERM HOSPITALIZED PATIENTS WITH TUBERCULOSIS *Tuberculosis Research Committee (Ryoken) (Chair:Teruo AOYAGI) In 1975, the Tuberculosis Research Committee (Ryoken) conducted its first study on long-term hospitalized TB patients who had been staying in a hospital for more than five years. Similar studies were repeated in 1981 (hospitalized for more than three years), 1988 (hospitalized for more than two years), 1993 and 1998 (hospitalized for more than one year). The same patient cohorts in each study were followed up, each after a differ- ent time period, i.e., after 68 months for the 1975 study cohort, 36 months for the 1981 study cohort, 26 months for the 1988 study cohort, and 74 months for the 1993 study cohort. Based on the results of these series of studies, changes in the patients' characteristics and factors related to long-term hospitalization during the last 23 years were analyzed. The main findings are summarized below. 1) The proportion of patients who stayed in a hospital for more than one year in the study decreased from 41.6% in 1975 to 9.5% in 1998. 2) The long-term hospitalized patients have become older, are more likely to be previously untreated cases, and initially bacillary cases. 3) The major cause of the treatment failure among the long-term hospitalized cases as reported by the attending doctors was "too chronic disease" in the earlier years, but the causes have changed to adverse reactions to anti-TB drugs, initial drug-resistance, and patient's poor compliance or non-adherence to treatment in recent years. 4) The cause of the long-term hospital stay after bacteriological negative conversion was chronic respiratory failure in more than one third of the patients in every study. Among these patients, an increasing proportion of cases has non-medical problems, such as poor family acceptance and reluctance to be discharged. 5) The mortality of the long-term hospitalized cases was generally high. Among bacteriologically positive cases in the study, it was 14% to 19% annually, and tuberculosis deaths occupied 60% to 80% of all the deaths. 6) The outcomes of those patients who were eventually discharged has become less favorable. Only 3% of them were returned to light work in the 2000 study, while 15% did in the 1981 study. Key words:Tuberculosis treatment, Long- term hospitalization, Follow-up study *C/o Research Institute of Tuberculosis, 3-1-24, Matsuyama, Kiyose-shi, Tokyo 204-8533 Japan. (Received 7 Dec. 2000/Accepted 15 Dec. 2000) <4>Kekkaku Vol.76 No.2:71-75,2001 A CASE OF TUBERCULOUS PERICARDITIS DEVELOPING CONSTRICTIVE PERICARDITIS *Hiroshi MIZUTANI, Michiaki HORIBA, Joh SHINDOH, Tomoki KIMURA, Masami SON, and Keiko WAKAHARA *Department of Respiratory Medicine, Ogaki Municipal Hospital A case of constrictive pericarditis which developed after the onset of clinical manifes- tation of tuberculous pericarditis was reported. A 75-year-old male, complaining of anorexia, was admitted to our hospital. Adenosinedeaminase (ADA) level in pericardial effusion was found to be increased, and the culture of pericardial effusion was positive for tubercle bacilli. Diagnosed as having tuberculous pleuritis and pericarditis, he under- went chemotherapy for tuberculosis. However, massive pleural effusion developed later and pleural effusion drainage was carried out. Despite repeated drainage, pleural effusion continued to recur. Chest CT revealed apparent pericardial thickening, in addition, cardiac catheterization revealed elevation of mean right atrial pressure and marked deterioration of cardiac functions including decrease of cardiac output. These findings were compatible with constrictive pericarditis. After these investigations a diagnosis of constrictive pericarditis was established, and the patient underwent a pericardiectomy. Pathological examination of resected specimens revealed tuberculous inflammation. Key words:Tuberculous pericarditis, Constrictive pericarditis, Pericardiectomy *4-86, Minaminokawa-cho, Ogaki-shi, Gifu 503-8502 Japan. (Received 28 Aug. 2000/Accepted 30 Nov. 2000) <5>Kekkaku Vol.76 No.2:77-81,2001 Commemorative Lecture of Receiving Imamura Memorial Prize PREVENTION OF DEVELOPMENT OF PULMONARY TUBERCULOSIS IN COMPROMISED HOST *Fumio YAMAGISHI *Division of Thoracic Disease, National Chiba Higashi Hospital Recently compromised hosts have increased due to aging of population, advance of medical technology and therapy or changes in the dietary life and social life. Concomi- tantly the proportion of compromised hosts in the patients with pulmonary tuberculosis has also increased. Taking up diabetes mellitus, hemodialysis, collagen disease and lung cancer as the representatives of compromised hosts, we studied the propriety of chemoprophylaxis to prevent the development of tuberculosis and the standard for the subjects in the case of chemoprophylaxis being given. Diabetics top the patients in the high risk group of developing pulmonary tuberculosis. Therefor, giving chemoprophylaxis is considered necessary to prevent the development of tuberculosis from diabetics. Chemoprophylaxis to diabetics should be given only when healing of tuberculosis has been found despite the history of treatment for tuberculosis being absent. In the patients of hemodialysis, the total morbidity of tuberculosis is high, but the morbidity of pulmonary tuberculosis is not too high, so chemoprophylaxis for the patients on hemodialysis is not always necessary. However, chemoprophylaxis according to the same standard for diabetics is necessary for the patients with diabetic nephropathy. In the patients with collagen disease except rheumatoid arthritis under consideration for administration of corticosteroid preparations, chemoprophylaxis is considered desir- able where doses of more than 10mg in terms of prednisolone are administered over a long period of time. In the patients with lung cancer under consideration for administration of corticosteroid preparations, chemoprophylaxis is considered desirable where doses of more than 10mg in terms of prednisolone are administered over a long period of time. Key words:Pulmonary tuberculosis, Compromised host, Diabetes mellitus, Corticosteroid, Chemoprophylaxis *673, Nitona-cho, Chuo-ku, Chiba-shi, Chiba 260-8712 Japan. (Received 21 Nov. 2000) <6>Kekkaku Vol.76 No.2:83-91,2001 The 75th Annual Meeting Special Lecture THE HUMAN IMMUNE RESPONSE TO MYCOBACTERIUM TUBERCULOSIS INFECTION AND DISEASE *Jerrold J. ELLNER, M. D. *New Jersey Medical School, University of Medicine and Dentistry of New Jersey *Newark NJ, 07103-2714 U.S.A. (Received 4 Dec. 2000)