[A DRG/PPS simulation in the medical care of tuberculosis].

PURPOSE: To study the expected usefulness of the introduction of the DRG-PPS (Diagnosis-Related Group/Prospective Payment System, in which an insurer pays a fixed medical fee per hospitalization) into the current medical care of tuberculosis (TB) in Japan. METHOD: The medical fees were reviewed for all TB inpatients at 19 hospitals under the National Hospital Organization who were discharged in either June 2007 or February 2008. The sum of the fixed fee by the DRG was assumed based on the bivariate regression analysis of each patient's hospital days and his or her total actual fees during the hospital stay under the current (fee for care) system, since it was difficult to directly calculate the daily fees for every patient that would be the basis of DRG-PPS. RESULTS: Linear regression analysis estimated that the medical fees (including fees for the medical examinations and the treatments) for a hospital stay of 60 days, which is the standard for TB treatment, was 1,192,470 yen (19,870 yen per person per day) in June 2007, and 1,167,600 yen (19,460 yen per person per day) in February 2008. DISCUSSION: If we assume an average medical fee of about Y1.1-1.2 million yen for the standard hospital care of TB, the economic balance of the hospitals is negative, with a deficit of 0.6-0.7 million yen, given the estimated expenses of 1.8 million yen (i.e., 30,000 yen per person per day x 60 days). CONCLUSION: If the DRG-PPS is to be implemented based on the current medical fee rating system, the hospital administrators could not accept its introduction to the TB medical care service as it is, because it may undermine the economic management of hospitals.

[Medical economics in tuberculosis management: what will come after the TB ward?].

Current unprofitability of medical services in tuberculosis (TB) ward in Japan has been induced by low medical fee and long-term hospital stays, aggravated by unoccupied beds due to the decrease in the number of patients. For the solution of this issue, the increase of medical fee, shortening of the length of hospital stay and drastic reduction of oversupplied beds are essential. An increment of medical fee by the change in the system would be appreciated, but even under the current system, the balance between revenue and expenditure could be obtained by reducing the length of hospital stay toward 4 weeks, and the elimination of deficit in TB ward could be accomplished by these efforts; shortening of length of hospital stay and reduction of TB beds. Although the latter might result in the difficulty of sustaining TB wards, these patients could be treated in the infectious disease ward. The integration of TB Control Law to Infectious Disease Control Law suggests that TB is not a special disease in Japan. If a true "short course therapy" era would be realized by novel anti-tuberculosis drugs, a dramatic change in TB management would occur in the near future.

[Specific immune-based diagnosis of tuberculosis infection].

Two blood tests have been developed that detect tuberculosis (TB) infection by measuring in vitro T-cell interferon (IFN) -gamma release in response to unique antigens that are highly specific to Mycobacterium tuberculosis. One assay, the enzyme-linked immunospot (ELISpot) [T-SPOT, TB; Oxford Immunotec; Oxford, UK], enumerates IFN-gamma-secreting T cells, while the other measures IFN-gamma concentration in the supernatant by enzyme-linked immunosorbent assay (ELISA) [QuantiFERON-TB Gold; Cellesist, Carnegie, Australia]. Clinical evidence indicates that both tests are more specific than the century-old tuberculin skin test (TST) because they are not influenced by prior Bacille Calmette-Guerin vaccination. Meta-analysis shows that pooled specificity was 97.7% and 92.5% for QFT and Elispot, respectively, and the sensitivity of these tests was suboptimal when newly diagnosed active tuberculosis was used as a surrogate for latent TB infection. These tests are considered to be superior to TST and will replace it for detecting TB infection.

[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.

[Clinical research on multi-drug resistant and extensive drug-resistant tuberculosis in Japan].

PURPOSE: To know the number of patients with MDR-TB and XDR-TB newly diagnosed annually and the number of those with continuously culture-positive in spite of continued treatment. METHODS: To fill the questionnaire sent to all the TB hospitals in Japan and to investigate the number of beds for TB, MDR-TB cases newly admitted to each hospital in 2006 and chronic bacillary cases in spite of continued treatment. RESULT: We sent the questionnaires to all the TB hospitals in Japan and 81% of 270 hospitals replied. As the result, 93 MDR-TB were newly hospitalized (12 cases were with XDR-TB). 76 cases of them were newly diagnosed MDR-TB. Almost after 1 year treatment, patients with XDR-TB showed lower negative conversion rate than other MDR-TB (42.9% vs 63.8%) and higher fatality rate (42.9% vs 7.2%). Excluding above 93 new MDR-TB cases, 103 cases with chronic MDR-TB including 44 cases with XDR-TB had been treated during the observation period, 84 case had been hospitalized and other 19 cases at OPD. DISCUSSION: Since 2000, extensive multi-resistant (XDR) TB has been a global topic. In Japan, nation-wide survey on 2002 showed the ratio of MDR and XDR were 1.9% and 0.6% respectively out of 3122 TB stains investigated. XDR/MDR rate was higher than those in other countries. Our clinical based investigation showed total XDR/MDR rate was 28.6% (56/196) and it was similar to that of previous bacteriological survey in 2002. CONCLUSION: We investigated the number of patients with MDR-TB and XDR-TB newly diagnosed in 2006 and the number of those who were continuously culture-positive. The survey showed that there were 196 patients with MDR-TB, and 56 patients of them (28.6%) were with XDR-TB. Many of them were in the districts of Kinki area and Kanto-Shinetsu area and 70% of them had been treated in the hospitals belonging to the National Hospital Organization.

[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.

[Tuberculosis complicated with liver cirrhosis].

OBJECTIVES: The aim of this study is to examine the clinical characteristics of tuberculous patients complicated with liver cirrhosis. MATERIALS AND METHODS: 44 patients (39 males and 5 females) admitted to Tokyo National Hospital since 1991 till 2005 were analysed. RESULTS: Eighteen patients died and liver failure was the leading cause of death (N = 10). Hepatitis C viral infection (N = 17), and excessive alcohol consumption (N = 13) were the major causes of liver cirrhosis. Twenty five patients followed-up for more than 3 months were further selected for the detailed analyses. Multi-drug combination chemotherapy including isoniazid, rifampicin and ethambutol was administered in 22 patients. Adverse effects were seen in 20 patients. The numbers of patients with leukopenia, thrombocytopenia and hyperbilirubinemia were 10, 9 and 3, respectively. They recovered following the alteration of chemotherapeutic regimen or drug desensitization. CONCLUSION: Tuberculous patients with liver cirrhosis are characterized with higher mortality rate and higher frequency of adverse effects of antituberculous chemotherapy. Multi-drug combination regimen could be tolerable under adequate surveillance of side effects even in the situation of preexisting liver dysfunction.

[Case of pulmonary mycobacterium avium complex disease, showing hypersensitivity pneumonitis-like diffuse shadow].

A 59-year-old man who had just completed therapy for tuberculosis, fell down in sauna and was admitted to a hospital. As acid-fast bacilli were positive (Gaffky 2) in sputum and residual cavity was shown in the right upper lobe on chest X-ray, he was transferred to our hospital. In spite of starting antituberculous chemotherapy, small nodular shadows appeared diffusely and were changed into ground-glass appearance on chest X-ray. The trans-bronchial-lung-biopsy revealed alveolitis mainly composed of lymphocyte infiltration with non-caseous epithelioid cell granulomas and organization which are likely to appear in hypersensitivity pneumonitis. As the acid-fast bacilli were identified as Mycobacterium avium, clarithromycin and kanamycin were added to the chemotherapy, but no improvement was observed in clinical feature. Corticosteroid therapy was further added and clinical feature improved immediately. Although we did not examine the presence of Mycobacterium avium in the water of sauna bath, we suspected this case as Hot Tub Lung based on clinical features and the response to treatment.

[Coexistence of lung cancer and active pulmonary mycobacteriosis].

OBJECTIVES: The aim of this study is to clarify the clinical and pathological anatomical picture of cases in which lung cancer and active pulmonary mycobacteriosis are intermingled in the same lobe of the lung. MATERIALS AND METHODS: We analyzed clinicopathological data on 11 cases in which lung cancer and active pulmonary mycobacteriosis are intermingled in the same lung lobe out of 61 admitted cases of coexisting lung cancer and active pulmonary mycobacteriosis, encountered at National Hospital Organization Tokyo National Hospital during the period from 1991 to 2003. RESULTS: The subjects were 10 men and 1 woman, with a mean age of 68 years. The species of mycobacteriosis were M. tuberculosis in 6 and nontuberculous mycobacteriosis in 5 (M. avium disease and M. abscessus disease in 2 each, and M. kansasii disease in 1). The frequency of the mixture was 13% (6/45) in patients with lung cancer and tuberculosis and was 31% (5/16) in patients with lung cancer and nontuberculous mycobacteriosis. Radiographic findings revealed that both cancer shadows and mycobacteriosis shadows are identified in 8 of the 11 patients, whereas cancer shadows were recognized but mycobacteriosis shadows could not be pointed out in the remaining 3 patients. We divided 7 cases (5 resection scases and 2 autopsy cases) with the mixture of cancer and mycobacteriosis into 2 types from the macroscopic images: (1) type A (4 cases, the foci of lung cancer and tuberculosis, which were separated originally, progressed mutually, and has adjoined), and (2) type B (2 cases, the foci of mycobacteriosis existed within or in the edge of the foci of lung cancer). There were 3 nontuberculous mycobacteriosis cases and 1 tuberculosis case in type A, and 2 tuberculosis cases and 1 nontuberculous mycobacteriosis in type B. In nontuberculous mycobacteriosis cases, cancer and mycobacteriosis had often adjoined under the conditions of preexisting lung disease, such as a lung cyst, whereas in tuberculosis cases, it was characteristically shown that the wall of encapsulated caseous nodules was destroyed by cancer invasion, and that the tuberculous nodules were reactivated. These findings seemed to be related to exogenous infection of nontuberculous mycobacteriosis to the injured lungs and to endogenous reactivation of tuberculosis from inactive tuberculous lesions. CONCLUSION: Lung cancer and active pulmonary mycobacteriosis are often seen intermingled in the same lung lobe, and the mixture pictures of the two diseases are variable. The physicians should carefully note about the mixture of lung cancer and mycobacteriosis, though the findings are not clear on the chest plain radiographs.

[A case of malignant mesothelioma showing rapid progression during one month].

A 57-year-old man with massive right pleural effusion was admitted to our hospital. Thoracoscopy revealed, fine granulations and small nodules scattered on the parietal pleura. Biopsy specimens suggested malignant mesothelioma. We performed thoracoscopy again one month later under general anesthesia to make a definitive diagnosis. At that time, the parietal pleura was covered with a large tumor and malignant mesothelioma was diagnosed by biopsy. We could find early pleural lesions of malignant mesothelioma in thoracoscopy. While we managed to make a definitive diagnosis, the tumor progressed rapidly during one month. If malignant pleural mesothelioma is suspected, it is necessary to make all efforts, including surgical biopsy, to diagnose during the early stage of disease.

[Capsular polysaccharide antibodies after pneumococcal polysaccharide vaccination in patients with chronic respiratory disease].

We investigated the antibody response to a 23-valent pneumococcal polysaccharide vaccine (23PSV), in 151 patients (average age: 70 years old) with chronic respiratory disease. Serotype-specific IgG antibodies to 4 pneumococcal capsular polysaccharides (6B, 14, 19F, and 23F) were analyzed by ELISA before, and one month after, 23PSV vaccination in all patients. Patients showed a significant increase in specific IgG levels to Streptococcus pneumoniae after 23PSV vaccination (5.5 times-20.9 times). Even patients aged over 80, patients with respiratory failure, and patients receiving corticosteroid therapy developed a significant immunologic response to 23PSV. Local pain or induration occurred in 9.1-14.3% and fatigue or chills occurred in 0.7-6.5% of patients. All adverse reactions disappeared in 2 or 3 days and there was no severe adverse events. Further studies are needed to confirm the exact protective antibody level and to examine the decline of antibody level after vaccination.

[A case of pulmonary aspergillosis with bone invasion and destruction in an AIDS patient].

A 59-year-old HIV-infected man who had been treated for pulmonary cryptococcosis in another hospital was suffering from pulmonary tuberculosis. He was admitted to our hospital for treatment of tuberculosis. The chest radiograph on admission showed a large cavity in the left lower lung field. Chest CT showed a mass like a fungus ball in the cavity. Pulmonary aspergillosis was diagnosed from the sputum mycology and serum immunoprecipitins. During the treatment of pulmonary tuberculosis and cryptococcosis, thickening of the wall of the cavity was seen together with adjacent bone destruction. In an autopsy, Aspergillus spp. Were found to have invaded the bone tissue and caused bone destruction. Pulmonary aspergillosis in an AIDS patient is infrequent, and is rare in additional association with bone invasion and destruction.