[A comparison of chest radiographs between patients with pulmonary Mycobacterium kansasii infection and those with Mycobacterium tuberculosis infection in the initial stage of disease].

OBJECTIVES: To elucidate the differences in affected lung segments between patients with pulmonary M. kansasii infection and those with M. tuberculosis infection in the initial stage of disease, we examined chest radiography images and CT scans. The initial stage of disease was defined as the period when less than one-sixth of the total lung area was affected by the infection, as visualized on chest radiography and CT. SUBJECTS AND METHODS: One hundred eighty-four patients were diagnosed with M.kansasii infection between 1996 and 2010 and 835 patients, with M.tuberculosis infection between 2008 and 2009 at our hospital. The diagnosis was made on the basis of the results of sputum culture and/or bronchial washing. After excluding the patients with underlying lung diseases such as chronic pulmonary emphysema, interstitial pneumonia, and old pulmonary tuberculosis as well as those in advanced stages, 24 patients with M. kansasii infection and 62 patients with M. tuberculosis infection were included in this study. The affected segments of the lungs and the rates of cavity development were determined by using CT scans. RESULTS: In patients with M.kansasii, 17 had an infected right lung, while 7 had an infected left lung. Additionally, in patients with M.tuberculosis, 58 had an infected right lung, 3 had an infected left lung, and 1 had a bilateral infection. In patients infected with M. kansasii, the upper lobes were affected in 22 cases and the lower lobes in 3 cases. In patients infected with M. tuberculosis, the upper, middle, and lower lobes and the lingular segment were affected in 41, 8, 24, and 1 cases, respectively. Upper lobe lesions were seen more frequently in patients with M. kansasii infection than in those with M. tuberculosis infection (p < 0.05). Cavity formation was identified more frequently in patients infected with M. kansasii (91.7%) than in those infected with M. tuberculosis (32.3%) (p < 0.001). Cavitary lesions were more frequently localized to the apical, posterior, and apico-posterior regions (S1, S2 or S1 +2) of the upper lobes in patients infected with M. kansasii (86.4%) than in those infected with M. tuberculosis (35%) (p < 0.001). A solitary lesion without endobronchial spread, which is characterized by centrilobular micronodules and tree-in-bud appearance, was more frequently demonstrated in patients infected with M.ka nsasii (45.8%) than in those infected with M. tuberculosis (6.5%) (p < 0.001). CONCLUSION: Our study revealed that the apical, posterior, and apico-posterior regions of the upper lobes are vulnerable to infection by not only M.tu berculosis, but also M.ka nsasii. It is likely that M.ka nsasii might gain access to these regions via the airways and that its weak virulence may lead to higher localization.

Chronological decrease of tuberculosis incidence rates by organ classification based on a birth cohort study in Japan, 1975-2005.

BACKGROUND AND OBJECTIVE: The incidence and annual risk of infection of tuberculosis (TB) have decreased rapidly in Japan because of the development of anti-TB medicines and nutritional and hygienic improvements after World War II. The incidence of tuberculosis is currently high among elderly people, reflecting the fact that the prevalence rate of TB infection had been extremely high during their youth. This would suggest that most current cases of TB in the elderly are reactivation of infections acquired in their youth. TB reactivation in various organs have both common and unique aspects. We evaluated the frequency of endogenous reactivation of TB in various organs by examining the TB incidence rate over a 30-year period (1975-2005) in Japan. METHODS: The incidence rate of TB in each organ was obtained for each 10-year birth cohort, using reports of newly registered TB patients in Japan in 1975, 1985, 1995, and 2005. Specifically, the incidence rates of pulmonary TB, lymph node TB, bone-joint TB, kidney TB, and meninges TB were analyzed. RESULTS: Chronological changes in TB incidence rates in each organ were characterized by a rapidly declining phase followed by a stationary phase in every organ TB except pulmonary TB. Incidence rates among the already infected population in the stationary phase were 3.0 (lymph node TB), 1.2 (bone-joint TB), 0.5 (kidney TB), and 0.3 (meninges TB) per 100,000 cases, respectively. CONCLUSIONS: Once infected with TB, the incidence rate of TB in these organs does not decrease below the above-mentioned values.

Doctor's delay in endobronchial tuberculosis.

OBJECTIVE: The aim of this study was to investigate the current status of doctor's delay in diagnosing endobronchial tuberculosis (EBTB) and to elucidate the risk factors contributing to the delay. METHODS: Retrospective clinicopathological analysis. PATIENTS: Sixty-two patients with EBTB were admitted at our hospital between 1999 and 2010. Their backgrounds, symptoms, diagnoses at initial consultation, delay in diagnosis, and clinical examination results were analyzed. RESULTS: Of the 62 patients, 59 had acid-fast, bacillipositive sputum smear test results at admission. Among the 40 patients with total diagnostic delay of more than 2 months, only 11 experienced long patient's delay exceeding 2 months. However, 22 patients experienced long doctor's delay of more than 2 months (28% vs. 55%, respectively, p < 0.05), suggesting that doctor's delay contributes more to total delay than patient's delay. Fever was less frequent in patients with long doctor's delays than in those without (0% vs. 18%, respectively), at the initial consultation. In addition, radiographs showed that patients with long doctor's delays more frequently presented with shadows in the lower lung field (50% vs. 23%, p < 0.05), and most of these patients had noncavitary shadows on admission. All 7 patients diagnosed with bronchial asthma at the initial consultation had long doctor's delays. CONCLUSION: These findings demonstrate that long doctor's delays in diagnosing EBTB remain an issue. The clinical features of EBTB with long doctor's delays were confirmed to be quite different from those of pulmonary tuberculosis.

[Tuberculosis care and new horizon of Japanese society].

Current tuberculosis (TB) problems are reflections of Japanese society. Living or dying alone among the elderly, difficulty in finding jobs or withdrawal into themselves among the youths are features of modem society. The future needs for TB care were discussed on specific topics of TB among the elderly, foreigners and the homeless. Presenters showed the importance of the patient-centered care in collaboration with public health and welfare services. Both patients and staffs will see others shining, as they touch each other in the deep part of human existence. A diabetic ex-TB patient talked his experience in his treatment. His window of mind was gradually opened from inside with the continuous support in DOTS by the staff of the public health center. To accumulate these experiences of a heartwarming atmosphere will have the effective power on establishment of social supporting systems. This symposium can be a step towards humanized society or a new horizon of public health which can answer to another need of inner cry of a sick people particularly among the socially disadvantaged who are the victims of the weakness of society. 1. Current situation and issues of elderly tuberculosis patients: Eriko SHIGETO (NHO Higashihiroshima Medical Center). By the analysis of 102 tuberculosis patients of 70 years old and above who were registered at Hiroshima Prefectural Health Center in 2009, 41 patients had severe complications such as diabetes mellitus, renal insufficiency, malignancy or cerebrovascular disorder. Their prognosis was rather poor and the ADL tended to be worsened during hospitalization. Though 16 of the 34 deaths were caused with non-tuberculosis diseases, the ratio of the tuberculosis deaths was higher (4/17) among the patients living alone. Sufficient care of the elderly for early diagnosis, care system to treat various complications and patient support are required. 2. Provision of medical interpreters to help foreigners with tuberculosis in Tokyo: Takashi SAWADA (Services for Health in Asian & African Regions (SHARE)). In 2006, Tokyo Metropolitan Government started to dispatch interpreters for foreigners to strengthen DOTS program. Collaboration with NGOs made it possible to train 37 volunteer interpreters, and to provide services in 13 languages, as of 2010. In Japan, the treatment defaulter rate among non-Japanese tuberculosis patients had been remarkably high. But with having the assistance of interpreters, the treatment completion rate has become higher than 80%. It is recommended to expand a similar system to other part of Japan, as the proportion of foreigners among total tuberculosis cases keeps on increasing nationwide. 3. Tuberculosis problems in Japan from the view point of homelessness-through the activities of a NPO supporting the homeless in collaboration with a public health center: Sadako KANAZAWA (Volunteer, NPO Medical Care Team of Shinjuku Renraku-Kai). It has been 20 years since the issue of homelessness emerged in Japanese society. The people with a history of both tuberculosis and experience of homelessness tend to show a poor prognosis. Our team has played an active role, working with Shinjuku Public Health Center for conducting a screening for tuberculosis every year. It seems that the screening service itself does not make a fundamental solution for homeless people with tuberculosis. Developing a more basic system of 'from street to apartment' is more essential. We believe that understanding the importance of the system is most essential to the people who are involved in health and medical care. 4. What we have learned from DOTS--Toward care by cuddling the patient's mind: Kazuyo ARIMA (PHN, Osaka City Public Health Center). Osaka City has achieved the goals of DOTS set up by the City's TB Control Guidelines since 2001 such as 80% DOTS implementation rate, halving the defaulter rate and incidence rate. It was shown by analysis that the treatment success depends on 'patient's awareness of the disease', 'appropriate DOTS method for each patient', 'existence of side effects', or 'the relationship between treatment supporters'. Through working for the patients whose treatment management was difficult, we have learned that our attitude towards the patients is a most important first step to build a good relationship and mutual trust with the patients, and DOT is an important tool. For treatment supporters,'the patient-centered care', 'care by staying close to the patients' or 'cuddling the patient' s mind' is most necessary to lead the patients to cure. 5. Patient's view: Through DOTS, my life has been renewed: Kuniyoshi MAEDA (Himawari no kai; Ex-homeless TB patients self-help group). It is an unforgettable memory that I was hospitalized due to TB back in 2009. I was seriously ill with also diabetes mellitus. Because I had lost everything due to my friend's cheating, I could not trust anyone before the TB treatment. But I learned how to think of others through the daily communication with doctors, nurses, other staff at the hospital, and Public Health Center. They encouraged me every day and I came to desire to answer to their expectations. Public health nurses taught me that building the reliable relationship is so essential for humans, and I may not have realized this importance if I had not been treated for TB, or treated outside Shinjuku. I would rather say that I was lucky to have got TB, as I have become able to trust other people through DOTS TB care. DOTS is not only for medication, but also general health care and counseling. I hope that as many as poor people, especially homeless can have a similar experience by knowing more about TB and using a health service. I would like to cooperate with TB services if I can be useful. health: Toshio TAKATORIGE (Graduate School of Safety Science, Kansai University). Tuberculosis was ever the biggest health problem in Japan. Ministry of Health and Welfare and Public Health Centers were founded to push forward tuberculosis control. Local governments, companies and people had to follow the national tuberculosis control program uniformly without exception. Currently a new stream of tuberculosis control has been started by DOTS strategy. The aim of DOTS has made all patients take medicine regardless of their social conditions until cure. Every patient is snuggled up and supported whether he is homeless, criminal or a foreigner. The patients also participate in the program actively. The DOTS may be a new public health movement. The strong public health infrastructure is necessary to maintain tuberculosis control towards the low incidence situation. The role of the local government should be more important. This symposium has also shown that the tuberculosis services must be patients-centered and supported by the people, addressing a new horizon of public health in Japan through tuberculosis control.

[Evaluation of tuberculosis treatment including levofloxacin (LVFX) in cases who could not continue standard regimen].

OBJECTIVE: The purpose of this study was to evaluate tuberculosis treatment including levofloxacin (LVFX) and to investigate the effectiveness of changing drug regimens at our hospital. SUBJECTS AND METHODS: A retrospective study was conducted on 331 patients with tuberculosis admitted to Tokyo National Hospital in 2005. Out of these 331 patients, LVFX was used in 48 (14.5%), 41 of which were initial-treatment cases. We studied why and how LVFX was used and compared bacteriological negative conversion rates between the initial-treatment cases in which the initial standard regimen was changed to regimens including LVFX, and those in which the initial standard regimen was either maintained throughout or modified with drugs other than LVFX. Sputum cultures were examined with Mycobacteria Growth Indicator Tube System (BACTEC MGIT 960). RESULTS: LVFX was used in 41 (13.6%) of 302 initial-treatment cases and in 7 (24.1%) of 29 retreatment cases. Out of the 269 initial-treatment cases starting with the standard regimen, LVFX was later used in 26 cases (9.7%). The reasons for using LVFX were adverse reaction to antituberculosis drugs in 23 cases (88.5%) and resistance to antituberculosis drugs in 3 cases (11.5%). We investigated the bacteriological conversion rate in 228 patients who could be followed up for more than five months. The conversion rates in 105 cases under the standard regimen including PZA (PZA+) were 92.4% in three months, 98.1% in four months, and 100% in five months. The rates in 56 cases under the standard regimen without PZA (PZA-) were 92.9 %, 98.2% and 100%,respectively. The rates of 22 cases under the initial regimen modified with LVFX (LVFX +) were 68.2 %, 95.5% and 100%, respectively. In 45 cases under the initial regimen modified with drugs other than LVFX (LVFX-), the rates were 80.0%, 97.8% and 100%, respectively. CONCLUSION: This study showed that LVFX was an effective drug in terms of the bacteriological conversion rate, without adverse reaction. LVFX is not approved as an antituberculosis drug in Japan, but it is often used in cases of MDR-TB or in situations in which the patients cannot continue treatment with the standard regimen. We hope that LVFX will be approved as an antituberculosis drug as soon as possible in Japan.

[A case of tuberculous pleurisy developing contralateral effusion during anti-tuberculosis chemotherapy].

A 55-year-old woman was admitted to our hospital because of chest pain, fever, and right pleural effusion that was exudative and lymphocyte-dominant with a high level of adenosine deaminase (ADA). Since her blood QuantiFERON-TB 3G test (QFT) was positive, she was diagnosed with tuberculous pleurisy. After initiation of anti-tuberculosis chemotherapy with isoniazid, rifampicin, ethambutol, and pyrazinamide, her symptoms improved. Later, liquid culture of the pleural effusion turned positive for Mycobacterium tuberculosis. On the 18th day of treatment, her chest X-ray and computed tomography exhibited pleural effusion in a moderate amount in the left thorax, with subsiding pleural effusion in the right thorax. Thoracocentesis demonstrated that the left thorax effusion was also exudative and lymphocyte-dominant, with elevated QFT response and high ADA concentration, suggesting tuberculous pleurisy. Mycobacterium tuberculosis was detected in the culture of a left pleural biopsy specimen obtained by thoracoscopy. We assumed that the left pleural effusion was due to paradoxical worsening because (1) on admission no effusion or lung parenchymal lesion was detected in the left hemithorax, (2) on the 14th day of treatment she was afebrile without pleural effusion on both sides, and (3) the bacilli were sensitive to the drugs she had been taking regularly. We performed drainage of the left effusion and continued the same anti-tuberculosis drugs, which led to the elimination of all her symptoms and of the pleural effusion on both sides. In conclusion, paradoxical worsening should be included in the differential diagnosis when contralateral pleural effusion is detected during the treatment of tuberculosis.

[Review of pulmonary Mycobacterium xenopi infection cases: 11 cases of our own and 18 other cases reported in Japan].

OBJECTIVE: To investigate clinical features of patients with pulmonary Mycobacterium xenopi infection treated at our hospital. SUBJECTS AND METHODS: We diagnosed 11 cases of M. xenopi infection at Tokyo National Hospital between 2000 and 2008 and recorded the drug susceptibility, patient characteristics, radiographic findings, treatments given and clinical courses. Eighteen other Japanese cases from the literature were discussed along with our findings. RESULTS AND METHODS: The cases of M. xenopi infection at our hospital consisted of 10 men and 1 woman with a mean age (+/- SD) of 55.1 +/- 19.4 years. Among the patients, 10 were smokers, 4 were heavy drinkers, and 6 had sequelae of pulmonary tuberculosis as an underlying disorder. Four patients had chronic obstructive pulmonary disease and 2 had diabetes mellitus, while there were 2 patients who had no underlying disease. All cases had radiographic opacities, predominantly found in the upper lung region, and cavernous lesions. These findings were demonstrated in both lungs in 5 patients, in the right lung only in 5 patients and in the left lung only in 1 patient. Concurrent aspergillosis was observed in 8 patients. The bacterial isolates from 7 cases were tested for drug sensitivity to levofloxacin (LVFX) and were found to be susceptible. M. xenopi disease was treated in 5 cases with INH+RFP+EB, in 2 cases with INH+RFP+Clarithromycin (CAM), and in 1 case with RFP+EB+CAM. Concurrent aspergillosis was treated with itraconazole in 2 cases. One patient underwent surgery for lung cancer. The duration of treatment was 16.4 +/- 12.8 months (range, 4-36 months). The radiographic findings were improved in 4 cases, deteriorated in 2 and unchanged in 5. M. xenopi was eradicated bacteriologically in 6 cases. The combination of radiographic and bacteriological findings indicated improvement in 3 cases, no change in 6 and deterioration in 2. DISCUSSION: The review of our cases disclosed that medical treatment alone was not sufficient in most cases for the control of clinical M. xenopi infection as reported overseas. Although we did not use LVFX for treatment, LVFX might be recommended for the treatment since all isolates tested proved to be susceptible to LVFX.

[Clinical investigation among elderly patients with tuberculosis].

OBJECTIVES: We discussed the factors which may confuse diagnosis and treatment of tuberculosis (TB) in elderly patients, in order to improve the situation. SUBJECTS AND METHODS: 414 patients who were hospitalized for active tuberculosis in Tokyo National Hospital were divided into three groups according to their ages (in years): less than 65, 65 to 74, and greater than 75. The three groups were compared in terms of performance status (PS), serum albumin level (whether over 3 g/dl or not), underlying diseases, symptoms at onset, sputum smear findings for acid-fast bacilli, presence or absence of cavitary lesion, regimen of treatment, adverse reaction to medications, and treatment outcome. RESULT: The older group had significantly poorer PS (3 or 4), lower albumin level, more complications, a larger proportion of non-respiratory to respiratory symptoms, less cavity formation, less likelihood of continuing to take drugs regularly and higher mortality. It is supposed that these characteristics are mostly due to the aging itself. CONCLUSION: Diagnosing and treating active tuberculosis among elderly people is difficult because of nonspecific and thus confusing findings due to other diseases or aging. Delay in diagnosis and start of treatment makes prognosis of their TB poorer. To improve this situation we should keep a high index to TB and make better use of novel diagnostic technologies. For satisfactory treatment that allows maintenance of a high level of activity of daily life, it is necessary to pay more attention to such aspects as nutrition and rehabilitation and to offer appropriate supports.

[A case of cold abscess of the chest wall due to thoracic drainage for tuberculous pleuritis].

A 56-year-old man underwent thoracic drainage for two weeks for tuberculous pleuritis. He was put on antituberculosis chemotherapy with INH (400 mg), RFP (450 mg), and EB (750 mg). Two months later, he developed an elastic hard subcutaneous mass in the area of the previous thoracic drainage. The mass was 10 cm in diameter, warm, reddish and painful. Chest computed tomography (CT) revealed localized and encapsulated empyema in the left thoracic space and a subcutaneous abscess with rim enhancement in the left lateral chest wall. Magnetic resonance imaging (MRI) demonstrated a dumbbell abscess in the subcutaneous tissue communicating with the empyema through the chest wall. A needle aspiration of the subcutaneous abscess had acid-fast bacilli smears of 2+ and tested positive by polymerase chain reaction (PCR) for Mycobacterium tuberculosis. Thus, he was diagnosed with a cold abscess of the chest, with the empyema in the thoracic space draining into the chest wall through the cut for artificial drainage. Continuation of the anti-tuberculosis treatment and the drainage of the empyema with repeated aspiration reduced the subcutaneous mass, and the clinical and radiological course was favorable. Both the smear and culture for acid-fast test became negative. After completion of chemotherapy, there has been no disease recurrence.

The value of fiberoptic bronchoscopy in culture-positive pulmonary tuberculosis patients whose pre-bronchoscopic sputum specimens were negative both for smear and PCR analyses.

OBJECTIVE: This study assessed the diagnostic rate of pulmonary tuberculosis (PTB) using fiberoptic bronchoscopy (FBS) in patients with suspected PTB, and negative pre-bronchoscopy smear and polymerase-chain reaction (PCR) in sputum. PATIENTS AND METHODS: We retrospectively reviewed 201 culture-positive PTB patients that underwent FBS because both smear and PCR results in sputum were negative. The positive rates of smear for acid fast bacilli, PCR for Mycobacterium tuberculosis, the presence of granuloma in transbronchial biopsy (TBB), and culture of M. tuberculosis were analyzed. In addition, the radiographic features, contribution of FBS to rapid and/or definitive diagnosis of PTB, and drug susceptibility results of M. tuberculosis were also reviewed. RESULTS: There were 136 males and 102 patients under the age of 40 years; non-cavitary (156 cases) and minimal disease (119 cases) on radiographs predominated. The positive rates of FBS were: 44% (smear), 62% (PCR), 61% (TBB), and 87% (culture). These rates increased in smear and PCR examinations when taken from wider spread shadows on radiographs. The combination of the various bronchoscopy samples increased the diagnostic rate to 92% when all examinations were combined. Positive culture results depended on FBS procedures in 80 cases. Twenty-one cases showed resistance to at least one of the major anti-tuberculous agents. CONCLUSION: This analysis revealed high positive rates of PTB from bronchoscopy samples, providing rapid and definitive ability for PTB diagnosis, and details of drug susceptibility. Therefore, FBS is an important diagnostic procedure in patients with suspected PTB whose sputum specimens were negative both for smear and PCR analyses.

[A case of tuberculosis with multiple lung nodules, abdominal lymphadenopathy, and splenomegaly].

Abdominal tuberculous lymphadenitis is very rare. We report a case of pulmonary tuberculosis showing marked abdominal lymphadenopathy and splenomegaly. A 95-year-old man was admitted to our hospital because of abnormal chest X-ray and body weight loss in last 6 months. He had low grade fever with no abdominal pain. He did not have past history of tuberculosis. Laboratory examination showed mild renal dysfunction and mild glucose intolerance. Soluble interleukin 2 recepter was highly elevated (3800 U/ml). Tumor markers, such as carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA), and progastrin-releasing peptide (Pro GRP) were all within normal limit. Chest X-ray showed multiple nodules in bilateral lung fields. Chest computed tomography showed multiple nodules in bilateral lungs, especially in upper part of lungs, right hilar lymphadenopathy and upper mediastinal lymphadenopathy. Abdominal and pelvic enhanced computed tomography showed marked abdominal lymphadenopathy and splenomegaly (67 x 49 mm). Abdominal lymph nodes were hepatoduodenal (50 x 50 mm), splenic hilar (40 x 25 mm), upper paraaortic (30 x 60 mm), and small superior mesenteric (10 x 10 mm) lymph nodes. FDG-PET showed accumulation in the nodules of right lung field, right hilar lymph nodes, upper mediastinal lymph nodes, and abdominal lymph nodes. Bronchial lavage fluid (BAL) smear for acid-fast bacilli was positive, polymerase chain reaction for Mycobacterium tuberculosis was positive and acid-fast bacilli was cultured. Transbronchial lung biopsy specimen demonstrated non-specific intraalveolar organization and alveolitis. The patient was diagnosed as pulmonary tuberculosis, but about abdominal lymphadenopathy and splenomegaly we had to differentiate malignant lymphoma, and for definite diagnosis, laparotomy was necessary. But considering his age and general condition, we followed up carefully with anti-tuberculosis therapy. Pulmonary tuberculosis, abdominal lymphadenopathy and splenomegaly all showed marked improvement 4 months after starting anti-tuberculosis therapy with isoniazid, rifampicin, and ethambutol, so we clinically diagnosed abdominal tuberculous lymphadenitis and splenic tuberculosis.

[Drug-induced hepatotoxicity caused by anti-tuberculosis drugs in tuberculosis patients complicated with chronic hepatitis].

OBJECTIVES: To investigate retrospectively the incidence of drug-induced hepatitis (DIH) caused by antituberculosis drugs including isoniazid (INH), rifampicin (RFP), with and without pyrazinamide (PZA), and to evaluate risk factors for DIH in tuberculosis patients complicated with chronic hepatitis (CH). MATERIALS: One hundred and seven tuberculosis patients with CH (M/F= 96/11, mean age +/- SE, 60.8 +/- 1.4 yr) admitted to our hospital during 1998-2006, whose laboratory data had been followed before and at least 2 months after starting antituberculosis chemotherapy, were enrolled in this study. Of these, 58 were being treated with anti-tuberculosis chemotherapy consisting of INH, RFP and PZA (HRZ group) and the remaining 49 with INH and RFP (HR group). For a case-control study, patients admitted to the hospital during the same period and without CH were selected to each CH patient (n=107) of the same gender, the same treatment regimens, and the same age. Clinical diagnosis of CH was based on laboratory data and in some cases pathological findings; etiology of CH was C-CH (CH caused by hepatitis C virus) in 68 patients, B-CH (CH caused by hepatitis B virus) in 23, and alcoholic CH in 16. METHODS: DIH was defined by elevation of serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) at 1 or 2 months after starting anti-tuberculosis chemotherapy. For patients with serum levels of AST or ALT already abnormally high before starting chemotherapy, an increase of > 1.5 times from the initial serum level was defined to indicate DIH, whereas for patients with AST and ALT within the normal range, and increase of > 3X the normal upper limit was defined to indicate DIH. The incidence of DIH was calculated separately in the groups HRZ and HR for patients with and patients without CH (control). In the HRZ group, the severity of DIH was defined by the maximum serum levels of AST and ALT, and their mean values were compared between CH patients and the control. Risk factors for DIH were examined by comparing patients with and without CH. The clinical course after development of DIH was also followed. [Results] The incidence of DIH in the HRZ group was 13/ 58 (22.4%) for CH patients and 10/36 (27.8%), 2/13 (15.4%) and 1/9 (11.1%) for C-CH, B-CH and alcoholic hepatitis patients, respectively, which was significantly (p < 0.05) higher than that in the control [4/58 (6.9%)]. Confining to the C-CH patients, the incidence of DIH was 10/36 (27.8%) compared with the control 2/36 (5.6%) (p < 0.05). In contrast, the incidence of DIH in the HR group was not significantly different between CH patients and the control, [2/49 (4.1%) vs 2/49 (4.1%)], respectively. The severity of DIH in the HRZ group estimated by the maximum level of serum AST and ALT was not significantly different in CH patients and the control (176.6 +/- 28.1 vs. 311.0 +/- 154.5 IU/L for AST and 187.8 +/- 19.1 vs. 277.8 +/- 72.4 IU/L for ALT). Of the 13 CH patients suffering from DIH caused by antituberculosis chemotherapy containing INH, RFP and PZA, 3 were continued treatment without altering the regimen, and 9 were continued treatment after changing the regimen to INH and RFP, omitting PZA. The one remaining patient was re-treated using INH, RFP and ethambutol (EB), but this again resulted in development of DIH, and he was ultimately treated with INH, EB and levofloxacin, with a successful outcome. Thus, at least 12 out of the 13 CH patients who developed DIH in the HRZ group could be treated by an anti-tuberculosis chemotherapy regimen containing INH and RFP excluding PZA. In C-CH patients who were treated with INH, RFP and PZA, the incidence of DIH was significantly higher when the daily alcohol intake was >20 g [8/18 (44.4%)] compared with those <20 g [0/10 (0%)] (p < 0.05), indicating that alcohol is a risk factor for DIH in C-CH patients treated with INH, RFP and PZA. CONCLUSIONS: In CH patients, anti-tuberculosis chemotherapy containing INH and RFP without PZA can be used safely. The inclusion of PZA in the regimen does substantially increase the incidence of DIH but nonetheless it can be used with caution, especially bearing in mind that daily alcohol intake of >20 g is a significant risk factor for C-CH patients.

[Usefulness of bronchofiberscopy for the diagnosis of pulmonary non-tuberculous mycobacteriosis--an analysis mainly on pulmonary M. avium complex disease].

OBJECTIVES: The aim of this study was to evaluate the usefulness of bronchofiberscopy (BFS) in the diagnosis of pulmonary non-tuberculous mycobacteriosis (PNTM). MATERIALS AND METHODS: Among 909 PNTM patients admitted to our hospital during the period from 1995 to 2006, BFS was performed for the diagnosis of PNTM in 107 patients (12%) who had either a negative sputum-smear for acid-fast bacilli (AFB) (n = 100) or from whom it had been impossible to collect sputum (n =7). For these 107 cases, we retrospectively compared and analyzed the findings from specimens obtained by BFS, such as smears, cultures, polymerase-chain reaction (PCR), and transbronchial lung biopsy (TBLB), with clinical, radiological, and sputum examination disease, was also seen in the positive ratios of other nontuberculous mycobacteriosis cases. Type and/or spread of MAC disease on chest radiographs did not relate to positive ratios of BFS obtained specimens. Based on overall BFS findings, including the examination of sputum immediately after BFS, 68 of 92 (74%) patients met the diagnostic criteria of MAC disease. Furthermore, through a combination of positive-TBLB findings and positive-PCR findings of BFS specimens, we were able to obtain an early and strong indication of MAC disease in 17 of 36 (47%) patients. CONCLUSION: Using BFS to obtain various kinds of specimens is a useful tool for the early and definite diagnosis of PNTM/pulmonary MAC disease.

[A case of primary pulmonary cryptococcosis presenting with acute respiratory failure].

A 71-year-old previously healthy woman, presented with respiratory failure several days after initiation of cough and fever. A chest X-ray revealed multiple infiltrative shadows with airbronchograms in bilateral middle and lower lung fields. Transbronchial lung biopsy, performed after steroid pulse therapy which induced transient improvement, demonstrated exudative lesions with massive aggregation of histiocytes containing yeast-like fungi in their cytoplasm. Since the test for cryptococcal antigens was positive, a diagnosis of primary pulmonary cryptococcosis was made. Despite intravenous fluconazole injection for aweek, the severity of fungus infiltration increased. The treatment was therefore changed to a combination of intravenous amphotericin B and oral prednisolone, which achieved clinical improvement. In conclusion, in the case of rapidly progressive pulmonary cryptococcosis with widespread exudative lesions, addition of steroid therapy should be considered when antifungal agents alone prove ineffective.

[Usefulness of a whole blood interferon gamma assay (QuantiFERON-TB-2G) for detecting tuberculosis infection in HIV-infected persons].

BACKGROUND: New blood test (QuantiFERON-TB-2G: QFT-2G), based on detection of IFN-gamma released by T cells in response to M. tuberculosis specific antigens, has the high sensitivity and specificity for diagnosis of tuberculosis. However, it is essential to evaluate this T cell-based approach in individuals with HIV-associated impairment in T cell immunity. METHODS: We assessed the usefulness of QFT-2G on diagnosis of tuberculosis in 13 HIV-infected patients with tuberculosis and the performance of 25 HIV infected persons under highly active antiretroviral treatment (HAART). QFT-2G, CD4 counts, and tuberculosis skin test and so on were examined. RESULTS: The sensitivity of QFT-2G in HIV-infected patients with tuberculosis was 76.9%, which was significantly higher compared with tuberculin skin test, 15.4%. There was one indeterminate case of which CD4 count was 16/microl, the lowest count among the all patients. CD4 counts of 25 HIV infected persons under HAART were between 100 and 1157/microl. There were 3 QFT-2G positive cases among them, who had past history of tuberculosis. CONCLUSION: Although the very low CD4 counts in HIV-infected patients might adversely affect QFT-2G performance, the sensitivity of QFT-2G in the most of HIV-infected patients with tuberculosis was high, and it was thought that it was useful enough to diagnose tuberculosis infection. Careful observation is required in whether the recurrence of tuberculosis takes place among QFT-2G positive persons who have past history of tuberculosis.

[Features of bronchial tuberculosis--an analysis of 103 cases].

OBJECTIVES: The aim of this study is to clarify the features of bronchial tuberculosis. MATERIALS AND METHODS: We analyzed the clinicopathological data from 103 out of 4467 (2.3%) cases of culture positive tuberculosis admitted to the National Hospital Organization Tokyo National Hospital in the period from 1993 to 2004 in which bronchial tuberculosis was confirmed by bronchofiberscopy. RESULTS: There were 62 women and 41 men, and 53 cases were less than 50 years old. The most common symptom, namely cough was observed in 70 cases, while 79 cases showed III1 to III2 on roentgenographic examination, and 81 cases were smear-positive for acid-fast bacilli in the sputum. Regarding the bronchofiberscopic findings, ulcers were detected in 60 cases, and the major site of bronchial tuberculosis was in the left main bronchus (35 cases). The number of the cases in which the time span from the onset of symptoms to diagnosis took over 3 months was 29, and 26 of them were "doctor's delay" cases which had a history of medical consultation resulting in diagnosis and treatment of other diseases, such as bronchial asthma (7 cases). There were 41 cases in which the second bronchofiberscopic findings have been reviewed, and regardless of the length of the span from the onset to diagnosis, the first bronchofiberscopy mostly revealed ulcer within 1 month after the start of treatment for tuberculosis, and 3 months after the start of treatment, many patients developed fibrous scars. Between 1999 to 2004, the first bronchofiberscopies were usually performed within 2 weeks to 1 month after the start of the treatment in contrast to the cases admitted between 1993 to 1998 in which bronchofribroscopy was mainly performed before the start of the treatment. However, there were no differences in the findings due to the timing of bronchofiberscopy. CONCLUSION: The clinical characteristics of bronchial tuberculosis have not changed, and the delay of diagnosis of bronchial tuberculosis due to doctor's delay also continues to be an important issue today. In patients showing positive sputum smear for mycobacteria, the timing of bronchofiberscopy, although required upon medical examination, is considered to be more appropriately performed from 2 weeks to 1 month after the start of treatment from the view point of nosocomial tuberculosis infection control strategy.

[Examination of administrative dosage of cyclosporine during anti-tuberculosis chemotherapy including rifampicin].

AIMS: In the treatment of tuberculosis with rifampicin in patients treated with prednisolone and cyclosporine, we have to increase the dosage of these drugs. Although prednisolone dosage is recommended to be doubled, there is no established consensus about cyclosporine dosage. Our aim is to review the current situation at our institution regarding the dosage of cyclosporine administered to tuberculous patients after the addition of rifampicin to the treatment regimen. METHODS AND RESULTS: We reviewed patients' clinical status and how dosages of cyclosporine were altered during a course of tuberculosis treatment including rifampicin in 4 patients (2 interstitial pneumonitis, 2 collagen vascular disease) who were being treated with cyclosporine between 2001 and 2003. Prednisolone had been also administrated in all patients and the dosage was doubled from the beginning of the treatment. The appropriate dosage of cyclosporine was found to be 2.5-3.5 (average 3) times that of initial dosage, and it required 5-12 weeks (average 8.3) measurements of trough levels and 6-27 (average 12) weeks until appropriate trough levels were obtained. CONCLUSIONS: The appropriate dosage of cyclosporine was found to be approximately 3 times that of the initial dosage in all patients, but it required a long-term and frequent measurements of trough levels before reaching this goal. It seems that trebling the dosage of cyclosporine from the start of anti-tuberculosis chemotherapy will be an efficient way to achieve good clinical outcome.

[Bone and joint tuberculosis concurrent with tuberculosis of other organs].

OBJECTIVES: To study the characteristics of bone or joint tuberculosis (TB) accompanied by TB in other organs (especially the lung), and to study patients' and doctors' delay in detecting bone or joint TB. SUBJECTS AND METHODS: A retrospective study was conducted on 33 patients with bone or joint TB concurrent with TB of other organs, especially the lung, who were admitted to our hospital between 1981 and 2005. The patients were divided into the following three groups according to the organ of concurrent TB : (1) miliary TB group (N = 10), (2) pulmonary TB group (N = 19), and (3) other TB site group (N = 4). The relationship between bone/joint TB and TB of other organs was studied by comparing the three groups with respect to the time of appearance of musculo-skeletal symptoms or signs such as swelling and pain and that of symptoms or signs originating from other organs, such as cough, sputum, miliary pattern on chest radiograph and superficial lymph node swelling. RESULTS: The mean age (SD) of patients was 50.5 (18.9) yr, and the male to female ratio was 23 : 10. Among 33 patients, bone TB (including 18 spinal TB) was detected in 24 patients, joint TB in 14, and abscess in 3 (concurrent lesions in some patients). The mean intervals from onset of symptoms to consultation (patients' delay), from consultation to diagnosis (doctors' delay) and from symptom onset to diagnosis (total delay) were 5.5 (13.9), 3.4 (5.2) and 8.9 (13.9) months, respectively. (1) Bone/joint TB concurrent with miliary TB (N = 10) In 8 patients with mean age of 61.0 (17.4) yr, musculo-skeletal symptoms/signs preceded respiratory symptoms or appearance of miliary pattern on chest radiograph by 7.8 (7.2) (range; 1-24) months. The patients', doctors' and total delays were 0.4 (0.5), 7.3 (7.8), and 7.7 (7.6) months, respectively. In most cases, bone/joint TB was diagnosed after the onset of miliary pattern on chest radiograph. In one patient with simultaneous onset of musculo-skeletal and respiratory symptoms/signs (age 21 yr), the interval of total delay was 1 month, and in one patient with musculoskeletal symptoms which appeared six months later than respiratory symptoms (age 28 yr), the interval of total delay was 2 months. (2) Bone/joint TB concurrent with active pulmonary TB (N = 19). In this group, the mean age was 52.2 (17.1) yr, and males were predominant (M/F = 15/4). Active pulmonary TB was diagnosed by positive sputum culture in 13 patients, by positive sputum smear or PCR results in 4 patients, and by the clinical course in 2 patients. Ten patients (53%) had a previous TB history. Cavitary lesion was observed in 15 patients, and the upper lobes were predominantly involved on chest radiograph in 19 patients, indicating that the pulmonary TB was probably post-primary (reactivation) in all patients. In 9 patients with mean age of 49.7 (15.7) yr, musculo-skeletal symptoms/signs preceded respiratory symptoms by 14.1 (14.0) (range; 4-48) months. The patients', doctors' and total delays were 13.3 (17.8), 3.8 (6.6), and 17.1 (16.1) months, respectively. On the other hand, in 10 patients with mean age of 54.5 (18.7) yr, musculo-skeletal symptoms/signs and respiratory symptoms/signs appeared simultaneously, and the total delay was 2.7 (1.9) months. Twelve of 19 patients (63%) had complications such as diabetes mellitus, steroid use, and liver diseases. In cases with miliary or pulmonary tuberculosis, the total delay in diagnosis (Y) correlates positively with the time lag from onset of musculo-skeletal symptoms to respiratory symptoms/signs (X), and the regression line (Y = 0.94X + 2.3, r = 0.98, p < 0.001) was almost linear (Y = X), indicating that the diagnosis of bone/joint TB was made just after the diagnosis of miliary or pulmonary TB. (3) Bone/joint TB concurrent with TB of other sites (N = 4) In 2 female cases (21 and 28 yrs) with cervical lymph node TB, musculo-skeletal symptoms/signs and cervical lymph node swelling appeared simultaneously. In a 54-yr male patient, musculo-skeletal symptoms/signs appeared 5 years after appearance of testicular enlargement, and testicular TB was diagnosed by biopsy simultaneously. In a 33 year-old male patient, musculo-skeletal symptoms/signs appeared 7 months after the drainage of pleural and pericardial effusions (TB was not diagnosed initially), and then the diagnosis of bone/joint, pleural, and pericardial tuberculosis was made for the first time. CONCLUSIONS: In middle-aged or elderly patients with active bone/joint TB, miliary TB is sometimes caused by bacillemia originating from the infected bone/joint lesions. In cases with bone/joint TB and concurrent pulmonary TB, bone/joint TB and pulmonary TB are probably reactivated independently as a result of decreased systemic immunocompetence.

[Coexisting lung cancer and active pulmonary mycobacteriosis].

We reviewed 72 patients with coexisting lung cancer and pulmonary mycobacteriosis, and discuss the features and transition of these coexistent cases. There were 56 pulmonary tuberculosis (PTB) cases and 16 non-tuberculous mycobacteriosis (PNTM) cases, 62 men and 10 women, with a mean age of 69 years. In 43 cases, both diseases were concurrently detected, lung cancer was first detected in 19 cases, and mycobacteriosis was first detected in 10 cases. The frequency of lung cancer in cases with active pulmonary mycobacteriosis was 1.2%. Pulmonary mycobacteriosis was characterized by Type II (40 cases) and Spread 2 (42 cases) on chest X-rays; the most frequent histologic type of lung cancer was squamous cell carcinoma (32 cases) and most were stage III-IV cases (57 cases). After PTB treatment, the negative conversion rate of sputum cultures in both the concurrently detected group and the group in which lung cancer was initially detected was 56% within one month and 94% within 2 months. For the treatment of lung cancer, 33 cases received supportive care, 13 patients underwent resection and 17 received chemotherapy or chemoradiotherapy. In PNTM cases, both lung cancer and pulmonary mycobacteriosis showed a slight state compared to those in PTB cases, and in the group in which lung cancer was initially detected, both diseases were more advanced or severe than those in the concurrently detected group or in the group in which mycobacteriosis was initially detected. The rate of coexisting lung cancer and pulmonary mycobacteriosis was unchanged at 1-2%, and the incidence of stage IV lung cancer cases has increased recently. Coexisting lung cancer and pulmonary mycobacteriosis is an important condition in respiratory disease in Japan. Physicians should be aware of the possibility of PTB coexisting with lung cancer.

Diagnosis of active tuberculous serositis by antigen-specific interferon-gamma response of cavity fluid cells.

BACKGROUND: To develop a more accurate methodology for diagnosing active tuberculous pleurisy, as well as peritonitis and pericardits of tuberculous origin, we established an antigen-specific interferon gamma (IFN-gamma)-based assay that uses cavity fluid specimens. METHODS: Over a 19-month period, 155 consecutive, nonselected patients with any cavity effusion were evaluated. Study subjects were 28 patients with bacteriologically confirmed active tuberculous serositis and 47 patients with definitive nontuberculous etiology. Culture was performed for 18 h with fluid mononuclear cells in the supernatant of the effusion together with saline or Mycobacterium tuberculosis-specific antigenic peptides, early secretory antigenic target 6 and culture filtrate protein 10. IFN-gamma concentrations in the culture supernatants were measured. RESULTS: In patients with active tuberculous serositis, antigen-specific IFN-gamma responses of cavity fluid samples were significantly higher than those of nontuberculous effusion samples. Area under the receiver operating characteristic (AUROC) curve was significantly greater for cavity fluid IFN-gamma response (AUROC curve, 0.996) than for cavity fluid adenosine deaminase and whole-blood IFN-gamma responses (AUROC curve, 0.882 and 0.719, respectively; P = .037 and P < .001, respectively). Although the AUROC curve was greater for cavity fluid IFN-gamma response than for background cavity fluid IFN-gamma level (AUROC curve, 0.975), the AUROC curves were not statistically significantly different (P = .74). However, multivariate logistic regression analysis revealed that cavity fluid IFN-gamma responses were significantly associated with the diagnosis, even after adjustment for background IFN-gamma level (adjusted odds ratio, 1.21; 95% confidence interval, 1.03-1.42; P < .001). CONCLUSIONS: The cavity fluid IFN-gamma assay could be a method for accurately and promptly diagnosing active tuberculous serositis.