[Mycobacterium immunogenum isolated from a metal worker in Japan].

In the United States and European countries, Mycobacterium immunogenum has been identified in metalworking fluids and is reported to be a causative agent of metalworking fluid-associated hypersensitivity pneumonitis. However, in Japan, there has been no reports of M. immunogenum isolated from metalworking fluids. This is the first report of isolation of the microorganism from the sputum of a metal-grinding machine worker in Japan. We should consider the possibility of M. immunogenum infection in case of non-tuberculosis mycobacteriosis and hypersensitivity pneumonitis in metalworkers.

[Clinical investigation of multidrug-resistant tuberculosis --investigation of inpatients in the Kyushu region between 2004 and 2009].

OBJECTIVE: To conduct a clinical investigation of patients with multidrug-resistant (MDR) tuberculosis who received either drug therapy alone or drug therapy in combination with surgery. SUBJECTS AND METHODS: A total of 56 patients with MDR tuberculosis who were admitted to hospitals of the National Hospital Organization in the Kyushu region between January 2004 and September 2009 and received drug therapy either alone or in combination with surgery were investigated. RESULTS: As surgery could not be performed in patients with advanced age or with bilateral extensive lesions, only 12 patients (21%) were able to undergo surgery. Initial drug resistance was seen in 10 patients (23%) in the drug therapy group and four patients (33%) in the combination therapy group. Underlying diseases included diabetes in 15 patients (34%) in the drug therapy group and in 6 patients (50%) in the combination therapy group. Negative conversion of the sputum culture result was observed in 43% in the drug therapy group and in 75% in the combination therapy group. The death within three years was seen in 20 patients (45%) in the drug therapy group and 1 patient (8%) in the combination therapy group. In the drug therapy group there were more cases with resistance to 5 drugs, resistance to levofloxacin (LVFX), and/or kanamycin (KM) in those who died of tuberculosis than in non-tuberculous death cases. CONCLUSION: Resistance to 5 drugs, resistance to LVFX, and resistance to KM were contributing factors of tuberculous death. Patient's operability was one of the factors associated with a good prognosis.

[A case of mild pulmonary tuberculosis complicated with the syndrome of inappropriate antidiuretic hormone secretion which caused impaired consciousness].

An 81-year-old woman was admitted to our hospital for hyponatremia and impaired consciousness after unsuccessful antibiotic treatment for pneumonia-like symptoms by a previous doctor. A chest X-ray film revealed unilateral infiltration. Mycobacterium tuberculosis was detected on a sputum smear and pulmonary tuberculosis was diagnosed. Based on the diagnostic criteria, we believed that her hyponatremia a consequence of syndrome of inappropriate antidiuretic hormone secretion (SIADH) as a complication of pulmonary tuberculosis. Sodium loading and water restriction quickly improved her serum sodium level and impaired consciousness. Anti-tuberculosis therapy reduced the abnormal shadows noted on chest X-ray films, and the sputum smear became negative for Mycobacterium tuberculosis. Her serum sodium level remained normal after the discontinuation of sodium loading. Previous reports have associated SIADH with severe types of tuberculosis such as miliary tuberculosis, tuberculosis meningitis, and pulmonary tuberculosis with massive bacterial excretion. However, this complication can also occur in mild tuberculosis, as in this case, thus SIADH should also be considered in mild cases of tuberculosis.

Relationship between computed tomography findings and nutritional status in elderly patients with pulmonary tuberculosis.

OBJECTIVE: This study was aimed to identify the relationship between radiographic features of elderly pulmonary TB patients and nutritional deficiency. METHODS: Ninety-two patients older than 70 years of age with pulmonary TB were retrospectively enrolled. The influence of nutritional parameters, such as serum albumin concentration and peripheral blood total lymphocyte count on CT findings was examined. CT findings of pulmonary TB patients were classified as those including atypical findings (segmental or lobar consolidation in an unusual location, miliary nodules, and hilar and mediastinal lymphadenopathy) or not. The number of segments involved by TB was also counted. RESULTS: Age- and gender-adjusted analyses for the nutritional parameters and confounders revealed that hypoalbuminemia, lymphocytopenia, and steroid therapy were significantly related to the presence of atypical CT findings. Furthermore, hypoalbuminemia, lymphocytopenia, and the amount of acid-fast bacilli in sputum smears were significantly related to an increased number of involved segments. In multivariate analysis, only hypoalbuminemia was significantly related to the presence of atypical CT findings (OR: 0.335, 95% CI: 0.142-0.794, p = 0.013) and an increased number of involved segments (OR: 0.145, 95% CI: 0.047-0.453, p = 0.0009). Among the CT findings, the tree-in-bud pattern was the most common in all patients (79.3%). However, the presence of the tree-in-bud pattern was not significantly related to any nutritional parameter. CONCLUSION: Elderly TB patients of poor nutritional status, in particular those with hypoalbuminemia, tended to show atypical CT findings and widespread lesions. The tree-in-bud pulmonary pattern could be observed in TB patients in any nutritional state.

[A case of pulmonary tuberculosis with diminished lung function whose paradoxical reaction led to death].

Paradoxical reaction in tuberculosis treatment is not generally fatal. On rare occasion it can lead a patient with diminished lung function and poor general condition to death. A 60-year-old man with history of left upper lobe resection from tuberculosis was referred to our hospital due to the recurrence of tuberculosis. Sputum examination showed a positive smear with a Gaffky score of 10, and the chest X-ray and CT revealed pulmonary infiltrate with many cavities (bII2) on the whole left lung field. Anti-tuberculosis drugs (isoniazid, rifampicin, ethambutol and pyrazinamide) were administered, but his high fever persisted, and the infiltrate on the chest X-ray deteriorated. While the positive sputum smear persisted, the culture became negative after one month. The tuberculous bacilli were susceptible to all anti-tuberculosis drugs in vitro. Though we performed examinations and trial treatments for non-tuberculous conditions such as pneumonia and drug-induced pneumonia, the patient died after 6 months. A necropsy specimen taken from the worsening lesion (the right upper lobe) as shown on the chest X-ray revealed many epithelioid granulomas. The patient had malnutrition, diabetes, alcoholic hepatic disorder, and insanity. It is supposed that although antituberculosis drugs were effective, a large quantity of killed organisms was continuously excreted from many cavities in the left lung toward the right lung. Lesions in the right lung thus newly produced in this paradoxical reaction seemed to reduce the remaining lung function. In addition, poorly controlled diabetes caused deteriorated heart function. These multiple factors contributed to the poor prognosis of the patient and his ultimate death.

[Clinical review of 8 patients with tuberculous peritonitis].

OBJECTIVE: With the progress of anti-tuberculous therapy, tuberculous peritonitis (TBP) has become a rare manifestation of active tuberculosis. Its early diagnosis is difficult due to lack of pathognomonic findings and specific symptoms. However, early diagnosis is important for effective treatment and for reducing fatality. MATERIALS AND METHOD: We retrospectively reviewed medical records of eight patients who were hospitalized with TBP in National Hospital Organization Omuta National Hospital during the periods between 2001 and 2009. RESULTS: Three patients were males and five were females. The age of the patients ranged between 28 and 80 years old (average 67.3 years). The most common presenting findings were abdominal distention seen in four patients and loss of appetite in five patients. Blood examination suggested that most patients were in poor nutrition. Three patients were diagnosed based on bacteriological examination, two based on histopathological findings of caseating granulomas, two based on the elevation of adenosine deaminase activity in ascitic fluid and one based on clinical diagnosis. The most common CT findings were thin lines along mesenteric vessels representing thickened mesenteric leaves and smooth uniform peritoneal thickening. Most patients were treated with isoniazid, rifampicin and ethambutol for 9 months with/without pyrazinamide initially. Seven patients completed anti-tuberculous therapy successfully and were cured. However, one patient died of the deterioration of tuberculosis. CONCLUSION: TBP should be considered for diagnosis, in patients with non-specific abdominal symptoms. Adenosine deaminase activity in ascitic fluid and CT images are considered to be useful for the diagnosis of TBP in patients in whom bacteriological and histopathological examinations are difficult to perform.

[The relationship between the nutritional states of tuberculosis patients at the time of their admission to tuberculosis wards and their treatment results].

OBJECTIVES: To prospectively investigate the relationship between the nutritional states of tuberculosis patients at the time of their admission to tuberculosis wards and their treatment outcomes. PATIENTS AND METHODS: We observed body mass index (BMI), peripheral blood lymphocyte count, serum albumin concentration, and induration size in the PPD skin test of a total of 107 tuberculosis patients after they had been newly admitted to NHO Omuta National Hospital during the period from Aug. 2004 to Jul. 2006. Based on these indices, the patients were divided into four groups according to their nutritional states: severely impaired, moderately impaired, mildly impaired or normal. RESULTS: It was shown that the worse the nutritional state was on admission, the higher the mortality rate from all causes including tuberculosis. There has been no relapse case in patients from this group who have completed tuberculosis treatment despite their poor nutritional states at the start of the treatment. CONCLUSION: This prospective study of the relationship between the nutritional states of tuberculosis patients on admission and their treatment outcomes reproduced the results obtained from a retrospective study that we had previously reported. The assessment method of the nutritional state that was used in our study was proven to be useful for predicting the prognosis of tuberculosis patients.

Nocardia transvalensis pulmonary infection in an immunocompetent patient with radiographic findings consistent with nontuberculous mycobacterial infections.

A chest roentgenogram of a 75-year-old immunocompetent woman showed disseminated micronodular densities in bilateral lung fields. Subsequent high-resolution computed tomography (CT) confirmed centrilobular micronodular densities associated with bronchial wall thickening and bronchiectatic changes. CT imaging also revealed volume loss with bronchiectatic changes in both the right middle lobe and the left lingular segment. Cytology specimens were then obtained through bronchial brushing and washes. Smears from right B2 and B4 revealed filamentous gram-positive, branched bacteria embedded among many neutrophils. Nocardia transvalensis was cultured from the bronchial wash, and no mycobacteria were identified. To our knowledge, this is the first report of a Nocardia transvalensis pulmonary infection in an immunocompetent patient, and also the first detailed description of a Nocardia transvalensis pulmonary infection in Japan. Moreover, the radiographic and CT findings in this patient were quite similar to those seen in patients with nontuberculous mycobacterial pulmonary infections, a pattern not previously reported in patients with Nocardia pulmonary infections.

Prognostic value of immunohistochemical surfactant protein A expression in regenerative/hyperplastic alveolar epithelial cells in idiopathic interstitial pneumonias.

BACKGROUND: It is difficult to predict survival in patients with idiopathic pulmonary fibrosis. Recently, several proteins, such as surfactant protein (SP) and KL-6, have been reported to be useful biologic markers for prediction of prognosis for interstitial pneumonias. It is not clear whether there is any relationship between expression of these proteins in regenerative/hyperplastic alveolar epithelial cells and prognosis of idiopathic interstitial pneumonias (IIPs). OBJECTIVES: This study aimed to elucidate the clinical significance of the expression of such lung secretory proteins as SP-A and KL-6 in lung tissues of patients with IIPs. METHODS: We retrospectively investigated the immunohistochemical expression of SP-A, KL-6, cytokeratin (CK), and epithelial membrane antigen (EMA) in alveolar epithelial cells in lung tissues obtained from surgical lung biopsy in 43 patients with IIPs, and analyzed the correlation between expression of these markers and the prognosis of each IIP patient. CK and EMA were used as general markers for epithelial cells. RESULTS: In patients with usual interstitial pneumonia (UIP), the ratio of SP-A positive epithelial cells to all alveolar epithelial cells (SP-A positive ratio) in the collapsed and mural fibrosis areas varied, ranging from cases where almost all alveolar epithelial cells expressed SP-A to cases where only a few did. On the other hand, in many patients with nonspecific interstitial pneumonia (NSIP), many of the alveolar epithelial cells in the diseased areas expressed SP-A. The SP-A positive ratio was significantly lower in patients who died from progression of UIP than in patients with UIP who remained stable or deteriorated but did not die. In NSIP patients, a similar tendency was noted between the SP-A positive ratio and prognosis. CONCLUSIONS: The results suggest that the paucity of immunohistochemical SP-A expression in alveolar epithelial cells in diseased areas (i.e. regenerative/hyperplastic alveolar epithelial cells) may predict a worse prognosis for patients with IIPs, especially patients with UIP. A prospective study is needed to confirm these results.

[Two cases of intravascular lymphomatosis diagnosed by transbronchial lung biopsy].

Patient 1 was a 54-year-old woman who was admitted with high-grade fever. Abnormal laboratory findings included hypoxemia, and elevated levels of LDH and soluble interleukin-2 receptor (sIL-2R). Chest computed tomography scans (CT) revealed diffuse ground-glass shadows in both lungs. Transbronchial lung biopsy (TBLB) confirmed the diagnosis of intravascular lymphomatosis (IVL). Patient 2 was a 46-year-old man who was also admitted with high-grade fever. Abnormal laboratory findings included slight hypoxemia, and elevated levels of LDH and sIL-2R. Chest CT images revealed diffuse, fine nodular densities in both lungs and several small nodules in the bilateral lower lobes. Perfusion scintigraphy revealed multiple defects in both lungs. TBLB specimens yielded a diagnosis of IVL. Although antemortem diagnosis of IVL is frequently difficult, it is necessary to perform TBLB in those patients who show fever not responding to antibiotics, elevated levels of LDH and sIL-2R, and hypoxemia.

[The relation between nutritional state of tuberculous patients admitted in tuberculous ward and their outcome at the time of discharge].

OBJECTIVES: To investigate the relation between nutritional state of tuberculous patients admitted in tuberculous ward and their outcome at the time of discharge. PATIENTS AND METHODS: We retrospectively investigated BMI, peripheral blood lymphocyte count, serum albumin concentration, and induration size of PPD skin test at the time of admission from their clinical charts of all 174 tuberculous patients newly admitted in NHO Omuta National Hospital during the period from 2000 to 2002, and based on these indices, the nutritional state of tuberculous patients was divided into severely impaired, moderately impaired, and mildly impaired or normal. The relation between nutritional state on admission and the outcome at the time of discharge was examined. RESULTS: The worse the nutritional state on admission, the higher the rate of death from all causes and tuberculosis, and the higher the average age and the duration of hospitalization. CONCLUSIONS: The assessment method of nutritional state reported in our study is easily applicable to every tuberculous patients admitted in tuberculous ward, and the outcome of tuberculous patients at the time of discharge could be expected, based on the nutritional state assessed with this method. Prospective study is needed to ascertain the validity of results obtained in the present study.

[A case of Streptomyces pneumonia].

A 85-year-old man who had a past history of gastrectomy but no subsequent chemotherapy was suffering fever and fatigue. The infiltrative shadow with cavitation on his chest X-ray film did not improve despite treatment with several antibiotics after admission. Transcutaneous needle aspiration performed for diagnosis of the cavitated lung lesion yielded Streptomyces. A definitive diagnosis of streptomyces lung infection was established. We believed that this is the first case of streptomyces infection of the lung reported in Japan. The current case was also rare because he did not have any immunosuppressive status, while almost all cases previously reported.

[A case of right paratracheal air cyst].

An 87-year-old female was being examined by her primary care doctor during a follow-up of 4 to 5 years after a diagnosis of non-tuberculous mycobacterial infection. An exacerbation of a shadow was suspected on a chest X-ray film, and therefore the patient was referred to our hospital. Her chief clinical symptom was mild occasional coughing, but no clearly abnormal findings were observed on the clinical examination. On chest CT, a cystic lesion was detected in the right posterodorsal side of the trachea at the level of the thoracic aperture, resulting in the diagnosis of a right paratracheal air cyst. Right paratracheal air cyst is a relatively rare disease, but it is believed that such a diagnosis can be made easily based on its localization and the CT findings, and it is a disease to which attention should be paid, which is why we are reporting it.

[Treatment outcome of patients with pulmonary tuberculosis before and after the induction of directly observed therapy (DOT)].

PURPOSE: To evaluate the treatment outcome of patients with pulmonary tuberculosis before and after the induction of DOT. METHODS: A retrospective study of the outcome of 239 tuberculosis patients treated during January 1996 to June 2003. We reviewed clinical charts collected on all patients with positive cultures for Mycobacterium tuberculosis. The patients of non-DOT group had received a traditional unsupervised drug regimen, before we have undertaken DOT. The patients of DOT group received therapy under direct observation by nurses. We compared sputum smear conversion period, sputum culture conversion period, duration of admission and treatment, recurrence rate, treatment success (cure and completion of treatment) rate and incidence of adverse effects between DOT and non-DOT group. RESULTS: Sputum conversion period and incidence of adverse effects were not significantly different between both groups. The duration of admission and treatment of DOT group was significantly shorter than those of non-DOT group. Rate of relapse and treatment success was not different between two groups. Over-80-year-old patients treated by DOT revealed a higher culture conversion rate after 2-month treatment than those who were not treated with DOT. CONCLUSION: We could not prove the usefulness of DOT during hospitalization for tuberculosis patients from the points of treatment success rate and relapse rate.

[Pulmonary alveolar proteinosis noted in a patient with thymoma].

A 74-year-old woman had general fatigue and mild fever in August 2004. Her chest X-ray showed slight ground glass opacities in the upper and middle lung fields of both lungs. Though she was prescribed antibacterial drugs, the abnormal shadows on chest X-ray did not improve. The chest CT showed ground glass opacities and reticular shadows with thickened alveolar septa (crazy-paving appearance) in both lungs, and a clearly defined mass in the anterior mediastinum. She underwent thymo-thymectomy with wedge resection of the upper lobe of the left lung. Anterior mediastinum tumor was pathologically diagnosed as thymoma. Lung biopsy demonstrated alveoli filled with SP-A positive granular materials, and we diagnosed pulmonary alveolar proteinosis. About 1 month after operation, the shadows on chest CT showed improvement. We think there might be some relationship between thymoma and pulmonary alveolar proteinosis.

[15 cases of pulmonary Mycobacterium scrofulaceum infection].

OBJECTIVES: We described clinical features of pulmonary Mycobacterium scofulaceum disease. MATERIALS AND METHODS: We described 15 cases of pulmonary Mycobacterium scrofulaceum infection admitted to National Hospital Organization Omuta National Hospital from 1989 to 2003 and reviewed the clinical feature, the findings of chest radiograph, and clinical course. RESULTS: Sex ratio was 8 male cases and 7 female cases, and the average age was 65.9 years old. Smoking history was found in 8 patients and occupational history of the dust inhalation was found in 7 patients with pulmonary M. scrofulaceum infection. There were 11 cases of tuberculosis-like form and 4 cases of nodular-bronchiectasis form according to the NTM Research society classification based on the findings of chest radiography. Improvement of the findings of chest radiography was seen in 4 patients by therapy, while no change or aggravation in 11 patients. Five patients died and among them, 3 died due to aggravation of pulmonary M. scrofulaceum infection. DISCUSSION: Cases showing tuberculosis-like form were dominant, and most of them showed extensive lesions when they were diagnosed, and these facts were considered to be major factors of difficulty in the treatment of this infection. The facts that 7 cases had occupational exposure to the dust, obstructive pulmonary disease in 3 cases, and 6 cases showed sputum culture positive for other nontuberculous mycobacteriosis, suggest that local resistance of lung might be attenuated, and this could be one of factors of onset and development of this infection. Only 4 cases showed improvement, while 5 cases died (primary disease death in 3 cases) and it was thought that the prognosis of the disease was in general poor.

[Two cases of Mycobacterium szulgai pulmonary disease in the elderly].

The rate of pulmonary nontuberculous mycobacteriosis (NTM) in the total pulmonary mycobacteriosis has been continuously increasing. While M. avium complex is the most common cause of NTM, there are a few case reports of pulmonary infection due to M. szulgai. We described two cases of pulmonary NTM caused by M. szulgai. A 75-year-old male was admitted to our hospital because of dyspnea on effort, and productive cough. A chest X-ray showed an infiltrative shadow with cavity in the right upper lobe. A sputum smear for mycobacteria was positive, and a culture grew M. szulgai which was identified by DNA-DNA hybridization. He was treated with isoniazid, rifampicin, and ethambutol. His symptoms and CT and X-ray findings improved, and his sputum smear and culture converted to negative for mycobacteria. Second case was a 73-year-old male who had previously been diagnosed as MAC and pulmonary aspergillosis, and had been treated with antituberculous and antifungal drugs. He was readmitted to our hospital, because of general fatigue and hemoptysis. A chest X-ray revealed a consolidation with bronchiectasis and cavity in the both upper lung fields. A sptum smear for mycobacteria was positive, and a grown culture was identified as M. szulgai. He was treated with rifampicin, ethambutol and kanamycin based on the results of susceptibility testing. After 3 months of this treatment his sputum smear and culture converted to negative for mycobacteria, and his symptoms, and CT and X-ray findings improved.

[Case of chronic eosinophilic bronchiolitis associated with bronchial asthma].

A 62 year-old woman presented with diffuse, centriacinar nodular densities on chest radiography and CT, and an increase of peripheral blood eosinophils, four years after diagnosis of bronchial asthma. Diffuse panbronchiolitis was diagnosed, and was treated with erythromycin for a long period. One year later, she noticed exertional dyspnea, and her chest radiograph showed increased nodular densities. Lung biopsy under video-assisted thoracoscopy was performed, and revealed chronic bronchiolitis with eosinophilic infiltration, and focal, peribronchiolar eosinophilic infiltration in the alveolar septa and alveoli. She was treated with prednisolone, and her symptoms and nodular densities on chest radiography and CT were improved. We consider that the clinico-pathological findings of this case are consistent with those of chronic eosinophilic bronchiolitis, which has recently been reported in Japan. This case is different from previously reported ones in that eosinophilic bronchiolitis appeared in the course of bronchial asthma, suggesting the possibility that eosinophilic bronchiolitis may be accompanied with bronchial asthma or eosinophilic pneumonia.

[A case of cervical and mediastinal lymph nodes tuberculosis, tuberculous pleurisy, spinal caries and cold abscess in the anterior chest wall].

A 61-year-old woman with schizophrenia that had been treated in a psychiatric hospital was admitted to our hospital because of subileus and back pain. Though subileus was improved, she had a sudden attack of fever 7 days later and developed right pleural effusion, a cold abscess in the anterior chest wall and swelling of a thumb-sized right cervical lymph node which broke through the skin. We made a diagnosis of cervical and mediastinal lymph nodes tuberculosis, tuberculous pleurisy, spinal caries and cold abscess in the anterior chest wall due to the biopsy findings of the specimen taken from the cervical lymph node, examination of pleural effusion, chest CT, bacteriological examination of the cold abscess and spinal MRI. We started chemotherapy with the antituberculous drugs (HRSZ) and symptoms except back pain improved. She complained of paresis of the both lower extremities, which completely paralyzed 8 months later in spite of continued chemotherapy. Thereafter her paralysis was gradually improved and she was able to walk by herself after 12 months chemotherapy.

[Immunological studies in cases of pulmonary Mycobacterium avium complex infection without predisposing conditions].

Peripheral blood mononuclear cells (PBMCs) taken from 39 primary pulmonary MAC patients and 11 control subjects were stimulated in vitro with a protein antigen PPD-B derived from M. intracellulare. Then, the activated response of the peripheral blood lymphocytes (PBLs) and the production of interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) were measured. The 39 primary pulmonary MAC patients were divided into A and B groups the former patients satisfying all of the criteria for the diagnosis of nontuberculous mycobacterial disease proposed by the American Thoracic Society, with the exception of the bacteriologic criteria, and the latter, who satisfied all without exception. The 39 patients were also divided into 3 groups according to disease severity judged from chest CT features. Severity in grades 1, 2 and 3 groups were mild, moderate and severe, respectively. We compared the activated response of PBLs and the production of IFN-gamma and IL-10 by PBMCs of the control group and each patient group. The number of lymphocytes and activated T cells and the concentration of the IFN-gamma after stimulation with PPD-B were lower in each group of primary pulmonary MAC patients than in the control group. IL-10 was significantly higher in each group of primary pulmonary MAC patients than in the control group (36.6 +/- 11.8 pg/ml), and higher in group B (131.6 +/- 14.9) than in group A (81.1 +/- 31.5). There was no significant difference in the IL-10 concentration between the grade 1, 2 and 3 groups. These results suggested that the cell-mediated immunity of primary pulmonary MAC patients was suppressed as the disease progressed, and the increased production of IL-10 was related to this suppression.