Evaluation of a simple loop-mediated isothermal amplification test kit for the diagnosis of tuberculosis.

OBJECTIVE: A new loop-mediated isothermal amplification (LAMP) test kit, including a simple DNA extraction device for the detection of Mycobacterium tuberculosis complex, was developed for commercial use and evaluated for its usefulness in diagnosing tuberculosis (TB). DESIGN: The LAMP test was performed using untreated and N-acetyl-L-cysteine (NALC) NaOH-treated sputum specimen. The efficiency of the kit was compared with other conventional laboratory examinations, including other nucleic acid amplification (NAA) tests. RESULTS: The sensitivity of LAMP using raw sputum (direct LAMP) in smear- and culture-positive specimens was 98.2% (95%CI 94.9-99.4), while the sensitivity in smear-negative, culture-positive specimens was 55.6% (95%CI 43.4-68.0). The diagnostic sensitivity of direct LAMP for the diagnosis of individuals with TB was 88.2% (95%CI 81.4-92.7). The sensitivity values of direct LAMP were slightly, but not statistically significantly lower than those of Cobas Amplicor MTB and TRC Rapid MTB, while the sensitivity of the LAMP test using NALC-NaOH treated sputum was significantly lower than other NAA tests (P < 0.05) for smear-negative, culture-positive specimens. The new commercial version of the LAMP kit was easy to handle and yielded results within 1 h of receiving sputum specimens. CONCLUSIONS: This test is considered a promising diagnostic tool for TB, even for peripheral laboratories with limited equipment, such as those in developing countries.

Seasonality in various forms of tuberculosis.

SETTING: Newly notified cases of tuberculosis (TB) for 5 years (1998 and 2000-2003) in Japan. OBJECTIVE: To study the seasonality of notification for various forms of TB. DESIGN: Descriptive analyses of newly notified cases by month of the year. Seasonal variations were compared among various forms of TB. RESULTS: In almost all the forms of TB examined, the numbers of newly notified TB cases were the lowest from November to January. For childhood and pleural TB, the numbers of cases of TB were highest from March to May (spring) and from April to June (spring to early summer), respectively. For sputum smear-positive pulmonary tuberculosis (PTB) in the young, the number of cases was also highest from March to May. For lymph node TB (except mediastinal) and sputum smear-positive PTB in the elderly (aged > or =50 years), the numbers of cases were highest from May to July (late spring to summer) and from June to August (summer), respectively. CONCLUSION: The seasonality of TB notification differs for the various forms of TB, which may reflect differences in the seasonality of clinical development of different types of TB disease such as primary, early and late post-primary TB.

Potential use of Amplicor PCR kit in diagnosing pulmonary tuberculosis from gastric aspirate.

Polymerase chain reaction (PCR) detection of mycobacteria from gastric aspirate for the diagnosis of tuberculosis is not fully evaluated up to now. A total of 116 gastric aspirate specimens were collected from patients with suspected pulmonary tuberculosis. The breakdown of diagnosis was 67 pulmonary tuberculosis, 16 nontuberculous mycobacterial infection, 5 extra pulmonary tuberculosis, and 28 other lung diseases. The conventional methods were shown to have a sensitivity of 47.8% and a specificity of 79.6%; on the other hand, Amplicor had 34.9% and 97.0%, respectively. The Amplicor provided a more rapid and specific method for diagnosing tuberculosis and was more useful than the conventional.

[Tuberculosis in Japan at present and in near future].

The high incidence of tuberculosis in the elderly people and no decrease in the incidence rate of the young people are two main features of current tuberculosis problem in Japan. To examine the near future prediction of the incidence rate and the rate of clinical breakdown by age group, the incidence rates of the newly registered tuberculosis cases of the cohorts born before 1918, in 1919-28, 1929-38, 1939-48, 1949-58 and 1959-68 were studied every ten years. The curves of incidence rate in each cohort were extrapolated to the future to obtain the incidence rates in 2008 and 2018. The numbers of predicted new cases in 2008 and 2018 were estimated to be some 31,000 and 23,000, respectively. The percentage of the cases above 60 y.o. was estimated to be 59%, 59% respectively. As the number of new cases in 1998 was 41,000, 55% of which was above 60 y.o., it will steadily decrease from now on, but the elderly people more than 60 y.o. will continue to occupy high percentage of the new cases. The incidence rate of the new cases will also decrease from 32.4 (per 100,000 populations) in 1998 to 24.5 in 2008 and 19.4 in 2018, and Japan in 2018 will still be a middle prevalence country in the world as now. The rate of clinical breakdown is obtained from dividing the incidence rate by the prevalence of tuberculosis infection. The latter is theoretically calculated from the annual risk of tuberculosis infection assuming that it doesn't depend on age. In Japan the annual risk of infection was supposed to be constant and about 4% till 1947. Since then it declined by some 10% annually till around 1977. Thereafter the annual speed of its decline was estimated to have slowed down. But we cannot know the true annual risk of tuberculosis infection, as BCG vaccination hinders the interpretation of the result of tuberculin skin testing in Japan. We postulated it declined 5% annually (Model A) or it was constant to be 0.17% since 1977 (Model B). Using these models of annual risk of tuberculosis infection, the prevalence of tuberculosis infection by age group was calculated in every calendar year. The incidence rate of each age group was assumed to be equal to that of median age in each age group. For example, the incidence rate of the cohort born in 1919-28 was assumed to be equal to that of the cohort born in 1923. In this way, the annual rates of clinical breakdown of the cohorts born in 1923, 1933, 1943, 1953, 1963 and 1973 were calculated. The rates of clinical breakdown for the cohorts born in 1923, 1933 and 1943 were similar with each other and were approximately 100 per 100,000 in both models. The rate of clinical breakdown at 25 years old for the cohort born in 1953 was 0.64 times smaller than that for the cohort born in 1943. It might due to the improvement of nutritional state and the effectiveness for adult tuberculosis of compulsory BCG vaccination which has been done after World War II in Japan. But for the cohort born after World War II, the later the cohort was born, the larger its rate of clinical breakdown was in both models. And, for example, the rate of clinical breakdown at age 25 years old for the cohort born in 1973 was 2.4 times (in Model A) or 1.7 times (in Model B) larger than that for the cohorts born in 1953. This may imply that there has been some factor(s) which facilitates tuberculous disease after tuberculous infection in young people in modern Japan. One explanation for this is the possibility that immune ability to tuberculosis might be weakened in young generations by some factor(s) such as environmental pollution.

[A study on the clinical features of pulmonary tuberculosis in elderly patients].

The clinical findings of pulmonary tuberculosis in elderly patients aged 75 years of age or older (elderly group) were compared with the middle-aged patients aged between 45 and 54 years of age (middle-aged group) and the young patients aged 34 years of age or younger (young group). The elderly patients who died in hospital were also compared with the elderly patients who survived. Study subjects were culture-positive pulmonary tuberculosis patients who were discharged from our hospital from December 1996 to November 1998. There were 79 patients in the elderly group, 95 in the middle-aged group, and 88 in the young group. The results were as follows. 1) The male/female ratio was significantly lower in the elderly group (1.9:1) than the middle-aged group (6.9:1). 2) Complication was noted more frequently in the elderly group. However, diabetes mellitus was noted less frequently in the elderly group (12.7%) than the middle-aged group (28.4%). 3) The frequency of cavitation was lower in the elderly group (59.5%) than the middle-aged group (87.4%). 4) The fever over 38 degrees C was noted less frequently in the elderly group (17.7%) than the other groups, while the frequency of the fever over 37 degrees C showed no significant difference between the elderly group and the other groups. 5) The frequencies of hypoalbuminemia and appetite loss were higher in the elderly group than the other groups. 6) The elderly group showed high mortality rate of 31.6%. The complication with cerebrovascular disease was noted significantly higher in the patients who died in hospital than those who survived. The frequency of widespread infiltrates, fever over 38 degrees C, neutrophilia, hypoalbuminemia and appetite loss were all significantly higher in the patients who died in hospital while their sputa were still positive on culture than those who survived. Our study clearly showed the features of elderly pulmonary tuberculosis patients in comparison with middle-aged patients and young patients. These features are very important to suspect the diagnosis of pulmonary tuberculosis in elderly patients with some atypical manifestation. Our study also suggests that the delay in diagnosing tuberculosis causes more frequently the patients' deterioration and death in elderly patients than in middle-aged patients and young patients.

[The causes of death in patients with non-MDR pulmonary tuberculosis in our hospital].

We studied the causes of death in 295 patients (mean (+/- SD) age 70.5 +/- 13.2 y.o.) with active non-MDR pulmonary tuberculosis who died in our hospital between 1991 and 1999. A hundred and twenty eight patients (43.4%, group A) died of tuberculosis, while 167 patients (56.6%) of other accompanying diseases. In 46 patients of the latter (15.6%, group B), pulmonary tuberculosis gave an unfavorable impact on their clinical course. In these patients the extent of pulmonary tuberculosis on chest roentgenograph was similar with the remaining 121 patients who also died of the accompanying diseases (41.0%, group C) and was less severe than those of the group A patients. Their nutritional conditions measured by serum albumin and choline-esterase level on admission, however, were as low as those of the group A patients and distinctly worse than those of the group C patients. Most patients of groups A and B died within 3 months after admission, while less than half patients of group C died during the same period. The age frequency distribution of the patients in groups B and C had a single peak in the age group 70 to 89, while that in group A showed two peaks, one similar peak as in groups B and C, and another peak in the age group 50 to 59. The numbers of homeless patients, of the patients with extensive cavitary lesions, and of the patients who died of ARDS (Adult Respiratory Distress Syndrome) or severe pneumothorax in group A were the most also in the age group 50 to 59, indicating that the patients' delay in admitting to hospitals was the major cause of high motality in this age group. As to detailed causes of death in group A, patients died of respiratory failure (32 cases), emaciation (28 cases), progression of pulmonary tuberculosis (20 cases), ARDS (15 cases), tuberculosis-related diseases such as pneumothorax, hemoptysis, and DIC (24 cases). In groups B and C patients died of organ failure (36 cases), infectious diseases (33 cases) and malignancy (30 cases). The total number of died patients has increased, and the proportion of cases dying of ARDS and infectious diseases has increased statistically significantly recently.

[HIV seroprevalence in patients with tuberculosis].

The number of patients co-infected with human immunodeficiency virus (HIV) and tuberculosis (TB) in our hospital is increasing year after year. Although most patients were HIV tested because of miliary tuberculosis or extra-pulmonary tuberculosis, some patients were found HIV seropositive by chance. In order to determine the incidence of HIV seropositivity among TB patients, HIV testing was carried out in TB patients for two years from January 1998 with the consent of patients. TB patients who received anti-HIV antibody examination were 164 in 1998, and 149 in 1999 and among them HIV seropositive TB patients were 4 in 1998 and 6 in 1999. The incidence of HIV seropositivity was 3.2% in all TB patients, 28.6% in miliary TB patients, and 1.0% in typical TB patients. The number of patients co-infected with HIV and TB in Tokyo was estimated by using these HIV seropositivity, it was 23 cases/year among miliary TB patients and 16 cases/year among typical TB patients. As there were many HIV-infected persons and many TB patients in Tokyo, it was thought that HIV testing in TB patients was important for the early detection of HIV infection and the early initiation of HIV treatment.

A stress distribution analysis of a ceramic lunate replacement for Kienbock's disease.

To determine the usefulness of a ceramic lunate replacement for the wrist joint as a possible treatment for Kienböck's disease, stress distribution of five wrist joint models (a normal wrist, one with the lunate bone removed, one with a coiled tendon replacement, one with a coiled tendon replacement with a ceramic core, and one with a ceramic lunate replacement coated with sheets of tendon) were analysed by the finite element method. The results of finite element method analyses were compared with those of pressure distribution analyses on the wrist joint using pressure-sensitive film and measurement of pressure on the radio-lunate joint with a tactile sensor. Both the coiled tendon model and ceramic core model were unable to resist applied force. Stress and pressure were well-distributed in the wrist joint of the ceramic lunate implant model. These results indicate that the ceramic lunate implant could be expected to prevent carpal collapse.

[Active pulmonary tuberculosis in patients with lung cancer].

To clarify the features of the coexistence of active pulmonary tuberculosis in patients with lung cancer, we analyzed clinical data on 25 cases with coexisting lung cancer and active pulmonary tuberculosis encountered at Tokyo National Chest Hospital during the period from 1991 to 1998. There were 23 men and 2 women, with a mean age of 70 years. The incidence of lung cancer among patients with active pulmonary tuberculosis at our hospital was 0.7 per cent, while the incidence of active pulmonary tuberculosis in untreated lung cancer patients at our hospital was 1.9 per cent. We classified the 25 cases into 2 groups as follows: (1) tuberculosis sequential to lung cancer (11 cases) and (2) tuberculosis concurrently detected with lung cancer (14 cases). All patients in the former group were transferred from other hospitals after diagnosing the coexistence of pulmonary tuberculosis during the management of lung cancer. Histological types of lung cancer were squamous cell carcinoma in 12, adenocarcinoma in 9, and small cell carcinoma in 4, and as to the disease stage, stages III to IV were predominant. Analysis on relationship of chest X-ray findings between lung cancer and pulmonary tuberculosis revealed that in general, the location of lung cancer and tuberculosis seemed to be independent. Tuberculosis in the sequential group was more extensive and severer than in the concurrent group. In the concurrent group, treatment for tuberculosis was successful except for one case, and coexisting tuberculosis did not seem to affect the course of lung cancer among this group. However, in the sequential group, 5 patients died within 3 months, 2 of them died of tuberculosis. We consider that in the management of lung cancer, physicians should consider the possibility of coexistent active pulmonary tuberculosis and should not make delay in the diagnosis of active pulmonary tuberculosis.

Optical resolution and absolute configuration of N-benzyloxycarbonyl-alpha-alkoxyglycines

Optical resolution of racemic N-benzyloxycarbonyl-protected alpha-alkoxyglycines, (+/-)-Cbz-Gly(OR)-OH (R = Et and Pr(i)), was achieved by means of fractional crystallization of diastereomeric salts with (+)-(1S,2S)-2-amino-1-phenyl-1,3-propanediol or diastereomeric esters of (+)- or (-)-menthol. The D- and L-configurations were assigned to the (+)- and (-)-Cbz-Gly(OR)-OH, respectively, based on L-enantioselective enzymatic hydrolysis of (+/-)-Cbz-Gly(OR)-OR' (R = Me, Et, and Pr(i); R' = CH(2)CF(3) and Me) using porcine pancreatic lipase and papain. Chiroptical properties and HPLC retention times of D- and L-Gly(OR)-residue (R = Me and Pr(i))-containing peptides were compared in relation to their configurational assignments. Copyright 1999 Wiley-Liss, Inc.

[Parameters relating to the development of residual pleural thickening in tuberculous pleurisy].

To identify predictive parameters for the development of residual pleural thickening in tuberculous pleurisy, we investigated 58 tuberculous pleurisy patients retrospectively who could be followed up until their chest roentgenogram no longer changed. The patients were divided into the following three groups according to the final configuration of pleural space: group I costphrenic angle (C-P angle) of the affected side was completely or almost completely recovered (20 cases), group II C-P angle became dull (20 cases), group III pleural thickening of > 2 mm remained in the lateral chest wall above the diaphragmatic dome level (18 cases). Differences of the clinical, chest roentgenographic and laboratory data were compared between these three groups. There were no differences between groups I and II in all of the parameters compared, while there were some differences between groups I and/or II and group III. The mean age of group III (51.1 +/- 18.1 y.o.) was significantly higher than that of group I (40.7 +/- 18.6 y.o.) and group II (34.7 +/- 14.7 y.o.) (p < 0.05 and p < 0.005 respectively). Glucose level in pleural fluid of group III (32 +/- 31 mg/dl) was lower than that of group I (96 +/- 13 mg/dl) and group II (86 +/- 21 mg/dl) (p < 0.001, respectively), while the levels of LDH, TP and ADA in pleural fluid were not different significantly among three groups. BSR (blood sedimentation rate) and CRP (C-reactive protein) were higher in group III (77 +/- 30 mm/hr and 8.5 +/- 4.3 mg/dl) than those in group I (45 +/- 23 mm/hr and 4.1 +/- 5.4 mg/dl) (p < 0.01 and p < 0.05, respectively). The level of albumin in serum was lower and that of globulin was higher, and consequently that of A/G ratio in group III (0.78 +/- 0.17) was lower than that of group I (1.15 +/- 0.16) and group II (1.10 +/- 0.22) (p < 0.001, respectively). It should be emphasized that the level of gamma-globulin was higher in group III irrespective of the presence or absence of accompanying pulmonary tuberculosis. Most patients more than 40 years old with serum A/G ratio less than 0.95 belonged to group III (13/15 (87%)) while most of those with serum A/G ratio more than 0.95 belonged to group I or II (10/11 (91%)). Thus hyper (gamma-) globulinemia and the intensity of inflammatory reaction in the whole body and in the pleural space are the predictive factors for the development of residual pleural thickening in tuberculous pleurisy.

Lung cancer in patients who had received thoracoplasty for pulmonary tuberculosis.

BACKGROUND: In Japan in the 1950s, thoracoplasty was a powerful therapy for pulmonary tuberculosis. Now there are many aged people who have tuberculosis sequelae caused by thoracoplasty. We have encountered some cases of lung cancer among these people. METHODS: To elucidate the features of lung cancer occurring after thoracoplasty for pulmonary tuberculosis, we reviewed for analysis 20 such cases. RESULTS: There were 17 men and three women, aged 55 to 78 years (mean 65 years). All had respiratory dysfunction and most were cigarette smokers. Lung cancers were located in the upper lobes in nine cases, in the middle lobe in one and in the lower lobes in 10. Ten lung cancers were in the thoracoplastied lung and the remaining 10 in the opposite lung. Histologically, squamous cell carcinoma was predominant (11 cases). Eight lung cancers were detected in stages I and II and 12 in stages III and IV. Most cancer lesions were separate from tuberculosis lesions. Surgical resection was selected in only three of 11 stages I-IIIA cases in consideration of respiratory dysfunction and/or ventilatory impairment due to thoracoplasty. Chemotherapy and/or radiotherapy were performed in nine and supportive care alone was performed in eight. Fourteen patients died of lung cancer and four died of cor pulmonale due to tuberculosis sequelae. Five-year survival was achieved in only one surgical case. Eight of the nine patients who received chemotherapy or radiotherapy died within 1 year, and, further, seven of eight patients who received supportive care died within 6 months. CONCLUSION: Lung cancer in the patients who had received thoracoplasty occurred in each lung and every lobe, independent of thoracoplasty. In addition, delay of detection was such that stage III-IV cases were in the majority, there were some limitations in therapeutic benefits related to thoracoplasty and the prognosis was very poor. Physicians should avoid delay in the detection of lung cancer through careful follow-up of such patients.

[Clinical review of 74 cases with miliary tuberculosis].

Seventy-four cases of miliary tuberculosis were studied retrospectively. The mean age of the patients was 45.3 years. Twenty-two patients suffered from another underlying diseases. Six were infected with human immunodeficiency virus. Twelve had been treated with corticosteroids. Fever was present in 97.3 per cent of patients. Elevation of serum alkaline phosphatase was found in 67.6 per cent of cases. The skin reaction to tuberculin was positive in 61.2 per cent. Nodular shadows were found in the chest X-ray in 98.6 per cent of cases. The nodules were smaller than 2 mm in diameter in 52.7 per cent of cases. Other findings were enlargement of mediastinal lymph node (17.6%), cavities (23.0%), pleural effusion (27.0%), and consolidation (35.1%). Sputum cultures and urine cultures were positive for Mycobacterium tuberculosis in 76.8 per cent and 58.6 per cent of cases respectively. The diagnosis was confirmed by histopathological findings in some cases. The rate of positive biopsies was 61.5 per cent by bone marrow aspiration, 83.3 per cent by lymph node biopsy, 100 per cent by liver and lung biopsy. Antituberculosis therapy was successful in most of the patients. Seven patients died of miliary tuberculosis, 4 of them had adult respiratory distress syndrome.

[Lung cancer in patients with sequelae of tuberculosis].

To clarify features of lung cancer in patients with tuberculosis sequelae, we analyzed data on 15 cases (5.1%) who were diagnosed with lung cancer before death among 294 deceased cases with tuberculosis sequelae at our hospital. There were 12 men and 3 women, with a mean age of 64 years. Most of the 15 patients had pulmonary dysfunction, and 4 had received home oxygen therapy. All 12 men had a history of smoking, and 10 of them had squamous cell carcinoma of the lung. There was no definite correlation between the locations of the tuberculosis lesion and those of lung cancer lesion on chest X-rays. Twelve patients had had thoracoplasty for tuberculosis, and in 6 of these patients the lung cancer occurred in the same lung. Lung cancer was apt to be diagnosed in an advanced stage. However, in patients who received home oxygen therapy, diagnosis had been made at an early stage because of the frequent chest X-ray follow-up. We conclude that lung cancer is an important complication in patients with tuberculosis sequelae, and early diagnosis of lung cancer by careful follow-up is essential in the care of cases with tuberculosis sequelae who have poor pulmonary function and/or systemic conditions.

[Long-term study of patients with pulmonary tuberculosis sequelae after bilateral thoracoplasty-airway obstruction and its causes].

Chest roentgenograms and results of pulmonary-function tests in patients with pulmonary tuberculosis sequelae 30 years after bilateral thoracoplasty were studied retrospectively to detect airway obstruction in these patients and to determine its causes. For periods of more than 10 years, vital capacity (VC) changed at a rate of 15.5 +/- 5.0 ml/year, and forced expiratory volume in one second as a percent of VC (FEV1%) changed at a rate of 0.546% +/- 0.380% per year (n = 13). Thirty years after thoracoplasty, the VC was 920 +/- 180 ml (%VC = 28.4% +/- 5.3%), and the FEV1% was 66.2% +/- 13.7% (n = 21). Thus, mild airway obstruction was found in about half of the cases. For each patient, the distance from the hilum to the diaphragm was measured along the mid-clavicular line on the side with fewer ribs resected, and this distance was divided by the patient's height. The results of that computation was found to be significantly and negatively related to FEV1% (r = -0.681, which suggests that longer bronchi in the lower and middle lobes on that side were associated with lower values of FEV1%. These findings are similar to those in patients with pulmonary tuberculous sequelae after total pneumonectomy. Over an average of 26 years, scoliosis, the vertebra showing the most bending, the intrapulmonary lesion, and the position of the diaphragm did not change, but the cardio-thoracic ratio increased.

[Small airway changes in acute interstitial pneumonia and acute exacerbation of chronic interstitial pneumonia].

To study pathologic changes in small airways in acute interstitial pneumonia (AI), changes in the terminal or respiratory bronchioles in one patient with AI and in three patients with acute exacerbations of chronic interstitial pneumonia (grouped together as the AI group) were compared to those in five patients with chronic idiopathic interstitial pneumonia (IIP) without acute exacerbation. Specimens obtained during autopsy were examined by light microscopy. In the AI group, mononuclear cells had infiltrated the lumen in 47 (23.7%) of the 198 bronchioles examined, and granulation tissue was found in 101 (51.0%). In the IIP group, no changes were found in 37 (97.4%) of the 38 bronchioles examined. Therefore, mononuclear cell infiltration and granulation tissue are common in the bronchioles of patients with acute interstitial pneumonia, but not in those of patients with chronic interstitial pneumonia without acute exacerbation.

[Long-term study of patients with sequelae of pulmonary tuberculosis after pneumonectomy--obstructive impairment and its causes].

Changes in pulmonary function, chest X-ray films, and CT were retrospectively studied in patients with sequeae of pulmonary tuberculosis 30 years after pneumonectomy (PNX). Over more than 10 years, VC and FEV1% changed at a rate of 23.2 +/- 8.8 ml and 0.683 +/- 0.688% per year, respectively. In the patients studied 30 years after PNX (N = 30), VC was 900 +/- 210 ml, %VC 31.6 +/- 8.1%, and FEV1% was 67.2 +/- 6.8%. About half of these patients had mild airway obstruction. FEV1% was negatively related to the distance from the hilum to the diaphragm on the mid-clavicular line (on the chest films) divided by body height (r = -0.607). Therefore, we think that the airway obstruction may be due to overextension of the bronchi of middle and lower lobes. Emphysema was not found in 18 patients who had no sign of hyperinflation or herniation of the remaining lung to the PNX side on their CT, but it was found in one patient with these signs.

[Association of active pulmonary tuberculosis and malignant diseases: a clinical study].

The association of pulmonary tuberculosis and bronchogenic carcinoma has been reported by many authors, however, there are rather few studies about the association of pulmonary tuberculosis and other malignant diseases and how the latter affects the outcome of the former. Between 1980 and 1993, we had in our hospital 104 patients who had both active pulmonary tuberculosis and malignant diseases. Pulmonary tuberculosis was diagnosed at the time or after the diagnosis of malignant diseases in 74 patients, of whom 92% (68 patients) were males and 42% (31 patients) were over the age of 70. There were 23 stomach cancer (31%), and 15 lung cancer (20%). In 11 patients tuberculosis developed after the initiation of radiation and/or chemotherapy. 67 patients could be followed up for more than 6 months after the initiation of chemotherapy for tuberculosis and the negative conversion rate was as high as 95.5% at 3 months. The fact indicates that the association of malignant diseases does not influence the course of tuberculosis and that these patients could be treated safely in general hospitals, provided the diagnosis is made properly without unnecessary delay.

Finite element analysis of pathogenesis of osteoarthritis in the first carpometacarpal joint.

Stress distribution in the first carpometacarpal joint was analyzed in 49 cadaveric hands using the finite element method to clarify the pathogenesis of osteoarthritis in the joint. The results of the finite element method analysis were compared with those of the contact pressure distribution in the first carpometacarpal joint of cadaveric specimens using pressure-sensitive film, and with the simple roentgenographical and microradiographical manifestations of spur formation, and with histological findings of osteoarthritis to verify the accuracy of the models of computer simulation models. The comparison of these results showed that osteoarthritic changes of the first carpometacarpal joint were found in areas where stress was concentrated during movement of the joint. The saddle shape of this joint is essentially well-designed for the dispersion of normal stress, however minimal displacement due to instability could easily induce osteoarthritis. Furthermore the shallow trapezial configuration may contribute to the high incidence of osteoarthritis changes. The finite element method helped clarify the relationship between stress patterns and osteoarthritis response.

[Small airway obstruction in patients with idiopathic interstitial pneumonia (IIP)--comparison between acute and chronic types].

Small airway obstruction in patients with acute and chronic interstitial pneumonia was studied. Patients with acute interstitial pneumonia (IP, n = 3), and with acute exacerbation of chronic IP (n = 4) were studied as a group, and were compared to patients with chronic idiopathic interstitial pneumonia (IIP, n = 41). Small airway obstruction was defined on a logarithmic %VC-V25/VC plane, because the V25/VC (an index of both small airway obstruction and decreased lung compliance) depended on %VC. Six of seven patients (86%) with acute IP and 8 of 42 patients (19.5%) with chronic IIP had small airway obstruction (p < 0.01). Small airway obstruction was often seen in acute IP, but was not often seen in chronic IIP.