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Background: Nontuberculous mycobacteria (NTM) are often detected in patients undergoing treatment for pulmonary tuberculosis. This clinical status is thought to represent NTM disease, contamination, or colonization, but discriminating between these three conditions is difficult., Purpose: We examined the clinical characteristics and pathogenicity of coexisting NTM among patients with pulmonary tuberculosis, as well as its impact on clinical practice., Patients and Methods: The subjects comprised 59 patients with pulmonary tuberculosis treated at the National Hospital Organization Utsunomiya National Hospital between January and December 2013. Patients in whom NTM was detected in one or more cultures were defined as the NTM group (19 patients), and they were compared to the non-NTM group (40 patients). Antiglycopeptidolipid (anti-GPL) core antibody titers were investigated in 18 patients from the NTM group., Result: We observed no significant difference in patient characteristics (age, sex, complications, history of pulmonary tuberculosis, lung disease, chest imaging findings, degree of smear positivity on admission) between the two groups. Mean duration of hospitalization was markedly longer for the NTM group, excluding those with coexisting NTM after discharge (98.8 ± 7.9 days), than for the non-NTM group (58.3 ± 3.5 days; p < 0.001). No anti-GPL core antibodies were detected in any of the 18 patients from the NTM group, including 13 patients who fulfilled the ATS/IDSA criteria., Conclusion: Coexisting NTM observed during treatment for tuberculosis likely results from colonization or contamination and usually has low pathogenicity. However, this finding is related to prolonged hospitalization.

The patient was a 27-year-old man with pulmonary tuberculosis, who was initially treated with isoniazid, rifampicin, ethambutol, and pyrazinamide. However, because of hepatic dysfunction and visual impairment, the four-drug therapy was switched to a three-drug regimen with isoniazid, rifampicin, and levofloxacin. At 9 weeks after the initiation of levofloxacin, the patient developed cervical lymphadenopathy, fever, systemic erythema, and hepatic dysfunction. He was diagnosed with drug-induced hypersensitivity syndrome (DIHS) based on positive results in the human herpesvirus (HHV)-6 DNA test, an indicator of HHV-6 reactivation. The symptoms improved after withdrawal of the antituberculosis drugs and initiation of steroid administration. However, considering the risk of relapse of DIHS, the tuberculosis treatment, which was initially planned for 9 months, was stopped at 7 months. Neither DIHS nor tuberculosis recurred.

Japanese guideline for the diagnosis and management of bronchial asthma was initially reported in 1998 and revised in 2000. This guideline was based on two former guidelines which were made by Japanese Allergology Society in 1993 and NIH.NHLBI in 1995 (GINA). New version of this guideline in 2000 pointed that the efficacy and adverse reaction of leukotriene receptor antagonists, the effectiveness of new inhaled corticosteroid (fluticasone propionate), and transdermal administration of beta-2 stimulant (tulobuterol hydrochloride). The precise evaluation of this guideline in terms of propriety, reliability, applicability and so on was not performed.

To analyze the pulsatile movement of coronary arterial walls, intravascular ultrasound was used to measure the diameter changes in the arterial lumen of 32 patients with coronary artery disease (CAD group) and five patients with chest pain but no CAD (control group). Measurements were performed on segments of the proximal left anterior descending coronary artery that were angiographically nonstenotic. Following identification of the peak systolic and end-diastolic phases using intra-coronary pressure tracings, the luminal diameters were measured around the center at 4 degrees intervals using a computer-assisted image analyzer. The pulsatile diameter change (dD) and end-diastolic diameter (DD) at each interval were analyzed and compared between the CAD and control groups. Mean DD did not differ significantly between the CAD group (4.53 +/- 0.69 mm) and the control group (4.52 +/- 0.51 mm). In contrast, the mean dD in the CAD group (0.05 +/- 0.18 mm) was significantly lower than that of the control group (0.13 +/- 0.12 mm). The mean maximum and minimum standardized percentage pulsatile diameter changes were -10.6 +/- 6.2% and 16.2 +/- 5.9%, respectively, in the CAD group, and -2.7 +/- 4.6% and 11.7 +/- 1.3%, respectively, in the control group. The mean standard deviation of dD was significantly greater in the CAD group (0.182 +/- 0.05 mm) than in the control group (0.116 +/- 0.04 mm), which indicated dD in CAD patients varied to a greater degree than in control patients. The ratio dD/dP (dP : pulse pressure) was used as an index of vascular compliance at the site of measurement. The mean dD/dP was significantly smaller in the CAD group (1.1 +/- 2.5 x 10(-3) mm/mmHg) than in the control group (4.0 +/- 3.3 x 10(-3) mm/mmHg). Aniso-diametric wall movement in the coronary artery (as indicated by a negative dD during systolic expansion) was enhanced in the CAD group compared to the control group. This was probably caused by the early stages of the arterial sclerotic process as it progressed heterogeneously along the vessel wall. Thus, aniso-diametric movement, which is a functional abnormality of the coronary arterial wall, appears to antedate detectable morphological changes.

A 26-year-old woman was admitted to our hospital because of fever of unknown origin. She had been treated with prednisolone, elcatonin and alfacalcidol under the diagnosis of systemic lupus erythematosus (SLE) and aseptic necrosis of femoral bone head. Six months ago she began to have a fever and subsequently left low back pain, for which extensive examinations were performed in other hospital but their causes remained unclear. She was referred to our hospital for further evaluation and therapy in October 1995. Bacteriological, immunological or serological examinations did not reveal the origin of fever. CT and ultrasonic examination did not show any abnormality. However, MRI, which was taken for the evaluation of aseptic necrosis of femoral bone head, showed the abscess shadow in sacroiliac joint. Open biopsy was performed and Mycobacterium tuberculosis bacilli were detected from the abscess. To our best knowledge, this is the first report of SEE with tuberculosis sacroiliac arthritis.

To determine whether IL-5 is locally produced in the bronchial mucosa of asthmatics, and to ascertain the precise cell type producing this cytokine, we examined bronchial biopsies by non-radioactive in situ hybridization and immunohistochemistry. IL-5 cDNA probes were labeled with digoxigenin-dUTP and hybridized to frozen or paraffin tissue sections. Hybridization signals were visualized by an immunohistochemistry technique. An IL-5-producing T cell clone derived from a patient with adult T cell leukemia was used as a positive control. Specific hybridization signals for IL-5 mRNA were observed in the bronchial mucosa of symptomatic asthmatics. No hybridization signal was detected in the control subject in whom no underlying disease was found. Immunohistochemical staining of serial sections using a panel of monoclonal antibodies directed against lymphocyte subsets strongly suggested that cells expressing mRAN for IL-5 were T cells. These results suggest that a cell-cell interaction between T cells and eosinophils through IL-5 may play an important role in the airway inflammation in asthma.

Eosinophils, which are prominent inflammatory cells in the asthmatic airway, are attracted to the airway by several chemoattractants. At present, eosinophil chemotaxis is studied employing the Boyden Millipore chamber system in vitro. In the Boyden method, the number of migrated cells are evaluated by direct microscopic observation of individual cells. This microscopic procedure usually requires much time and it is difficult to obtain objective results. Therefore, we have developed a new fractional measurement technique, using the image analyzing system connected with a color video camera and a computer for counting the eosinophils which have migrated into a filter. Using this system with the Boyden method, migrated cells were observed more objectively and quickly. Therefore, this image analyzing system with the Boyden method, may be a useful technique for the fractional measurement of migrated eosinophils in a sample mixture of eosinophils and neutrophils.

In order to clarify the role of leukotriene in the antigen-induced asthmatic response, we carried out mite-antigen, leukotriene D4 (LTD4) and histamine inhalation tests in 21 mite-sensitive atopic asthma patients, and investigated the relationship between the bronchial responsiveness to mite (PD20-Mite) and that to LTD4 and histamine (PD20-LTD4, PD20-Hist). We then compared PD20-LTD4 and PD20-Hist between the groups with and without late asthmatic response (LAR), and investigated the relationship between the peak percentage fall of FEV1.0 in LAR (magnitude of LAR) and PD20-LTD4 and PD20-Hist. There were significant correlations between PD20-LTD4 and PD20-Mite (r = 0.590, p < 0.01), and between PD20-Hist and PD20-Mite (r = 0.669, p < 0.001). The bronchial responsiveness to LTD4 and histamine was significantly higher in the group with LAR. In addition, PD20-LTD4 showed a significant negative correlation with the magnitude of LAR (r = 0.724, p < 0.001). Furthermore we analyzed the relationship between PD20-LTD and the ratio of the magnitude of LAR to that of IAR (immediate asthmatic response), because there was a significant correlation between the magnitude of IAR and that of LAR (r = 0.842, p < 0.001) in 16 asthmatic patients with dual asthmatic response, and found that the correlation coefficient was also very high (r = -0.836, p < 0.001). These results suggest an important role of leukotriene in the antigen-induced asthmatic response.

To evaluate the role of eosinophils in the pathogenesis of bronchial asthma, we measured eosinophil cationic protein (ECP), one of the eosinophil granule proteins. Serum ECP levels were measured by radioimmunoassay in asthmatic (n = 59) and non-asthmatic (n = 47) patients. Preliminary study showed that ECP levels were time-dependently increased in the blood samples until 3 hr. Based on the findings, we determined to measure serum ECP levels at 30 min after blood sampling. Serum ECP levels and blood eosinophil counts in asthmatic patients were significantly higher than those in non-asthmatic patients (p less than 0.01). There was also a positive correlation between serum ECP levels and blood eosinophil counts in patients with asthma (r = 0.46, p less than 0.001). No significant difference was observed in either serum ECP levels or blood eosinophil counts in asthmatic patients classified by clinical type and severity. Blood eosinophil counts in patients with asthma attacks were significantly greater than in those in remission (p less than 0.05), but no significant difference was observed in serum ECP levels between these groups, suggesting an enhanced elimination of ECP during attack. Serum alpha-2 macroglobulins, which bind to ECP and may function as scavengers for ECP, were not significantly different in these group. These results suggest that serum ECP levels may not be a direct indicator of eosinophil activation or degranulation in the pathogenesis of asthma.

To evaluate the acute effects of anti-asthmatic drugs in vitro, we examined the modulation of various anti-asthmatic drugs in therapeutic concentrations on PAF-induced human eosinophil chemotaxis. Aminophylline (20 micrograms/ml) and Isoproterenol (10 nM) inhibited PAF (3 X 10(-8) M)-induced eosinophil chemotaxis nearly 30%, whereas no inhibitory effects were observed by Dexamethasone (0.1 microM), Tranilast, Ketotifen or Azelastine. Aminophylline (20 micrograms/ml) also inhibited LTB4 (3 X 10(-8) M)-induced eosinophil chemotaxis nearly 30%, whereas it did not inhibit chemotaxis induced by zymosan (5 mg/ml)-activated serum. These results indicate that anti-asthmatic drugs except for aminophylline and isoproterenol, when used acutely in therapeutic concentrations, have no striking inhibitory effects on PAF-induced eosinophil chemotaxis. These results further suggest the possibility that there are different mechanisms in eosinophil chemotaxis induced by PAF, LTB4 or by C5a.

To elucidate the role of eosinophils, neutrophils and lymphocytes for the development of bronchial hyperresponsiveness (BHR) following antigen exposure, we have developed a guinea pig model of BHR. Guinea pigs immunized by repeated exposure to aerosolized ovalbumin (OA) were intravenously given metopirone, a cortisol synthesis inhibitor, 24 hrs before and 30 min before antigen challenge, and to prevent death from immediate severe bronchoconstriction, chlorpheniramine maleate was also injected. After antigen challenge with high dose of OA, LAR occurred in twelve of fifteen animals (80%) and the bronchial responsiveness to acetylcholine (Ach) was significantly increased. Histologic examination at 72 h showed a significant increase in the number of eosinophils but not neutrophils within the tracheal walls. However, there was no significant correlation between the change in bronchial responsiveness to Ach at 24 h and the number of eosinophil in the tracheal wall at 72 h. When guinea pigs were treated with Cyclosporin A or FK506, T-lymphocyte selective immunosuppressive agents, from the beginning of immunization period, both eosinophil infiltration and an increase in bronchial responsiveness were inhibited. These results suggest that eosinophils and T-lymphocytes may play an important role in the development of bronchial hyperresponsiveness.

We examined the effects of FK-506, a potent immunosuppressive agent, on the development of late asthmatic response (LAR) and on the increased bronchial responsiveness to acetylcholine following LAR in guinea pig model of asthma. Guinea pigs sensitized by repeated inhalation of ovalbumin (OA) were intravenously given metopiron 24 hours before and 30 minutes before antigen challenge and to prevent death from immediate severe bronchoconstriction, chlorpheniramine maleate was also injected. When we defined LAR as the responses with a two-fold increase in respiratory resistance during the late phase of antigen challenge, twelve out of fifteen control animals demonstrated apparent LAR. However, when guinea pigs were treated with FK-506 from the beginning of immunization period, the development of LAR was completely inhibited, although similar magnitude of immediate bronchoconstriction was observed, and a subsequent increase in bronchial responsiveness was significantly blocked. We also measured bronchial responsiveness to acetylcholine before, 24 and 72 hours after antigen challenge. FK-506-treated animals inhibited an increase in bronchial responsiveness to acetylcholine. These results suggest that the involvement of cell-mediated immunity may be important in the development of LAR and an increase in bronchial responsiveness.

Bronchial eosinophilia is a characteristic of asthma. To elucidate the mechanisms of eosinophil accumulation in the airways, the time course of eosinophil infiltration in the airway mucosa after antigen inhalation was examined in actively sensitized and passively sensitized guinea pig models of asthma. The lungs and tracheae were removed at intervals after antigen challenge, fixed and stained. The eosinophil infiltration was quantitated in the tracheal walls by counting the number of cells per square millimeter. Guinea pigs sensitized by intraperitoneal injection of ovalbumin (OA) responded to a single exposure to aerosolized OA with biphasic infiltration of eosinophils in the tracheal walls; a striking early-phase which peaked at 6 hr and a delayed-phase which peaked at 24 hr and persisted for as long as 5 days. These kinetics were different from those observed with passively sensitized animals which showed only early-phase infiltration. Administration of CV-6209, a specific PAF antagonist, before and 12 hrs after antigen challenge significantly (p less than 0.01) inhibited the early-phase but not the delayed-phase eosinophil infiltration in actively sensitized animals. In contrast, when guinea pigs were treated with Cyclosporin A, a T lymphocyte-selective immunosuppressive agent, throughout the immunization period, the delayed-phase but not the early-phase infiltration was significantly (p less than 0.01) inhibited. These results suggest that PAF may contribute to early-phase and T cell factor(s) may contribute to delayed-phase eosinophil infiltration of the airways.

We have previously demonstrated that Cyclosporin A (CyA), a T lymphocyte-selective immunosuppressive agent, reduced the delayed-phase bronchial eosinophil infiltration after antigen challenge in a guinea pig model of asthma. In the present study, we studied the effects of CyA on antigen-induced late asthmatic response (LAR) and bronchial hyperresponsiveness following LAR. Guinea pigs immunized by repeated exposure to aerosolized ovalbumin (OA) were intravenously given metopirone, a cortisol synthesis inhibitor, 24 hours before and 30 minutes before antigen challenge, and to prevent death from immediate severe bronchoconstriction, chlorpheniramine maleate was also injected. After antigen challenge with high dose of OA, LAR occurred in twelve of fifteen animals (80%) and the bronchial responsiveness to acetylcholine was significantly increased. However, when guinea pigs were treated with CyA from the beginning of immunization period, the development of LAR was completely inhibited, although similar magnitude of immediate bronchoconstriction was observed, and a subsequent increase in bronchial responsiveness was partially but significantly blocked. Since CyA has been shown to suppress activation of guinea pig T lymphocytes and their production of lymphokines, these results suggest that T cell factor(s) may be important for the elicitation of LAR and the antigen-induced bronchial hyperresponsiveness.

Respiratory infections of 19 subjects of advanced age and/or with underlying respiratory disease were treated with cefoperazone (CPZ) and its clinical effects were studied. Sixteen subjects suffered from respiratory tract infection and 3 subjects had pneumonia. The age of the subjects ranged from 39 to 77 years with the mean of 63.8, 7 of them being more than 70 years of age. The underlying respiratory diseases included chronic pulmonary emphysema in 6 subjects, diffuse panbronchiolitis in 3, bronchiectasis in 3, silicosis in 2 and one each of chronic bronchitis, pulmonary fibrosis, lung cancer and old pulmonary tuberculosis. One case, 75 years of age, had renal insufficiency. The daily dose of CPZ was 4 grams in 18 of the 19 subjects and the duration of administration ranged 5 to 22 days. The remaining 1 subject received 2 g of CPZ daily for 6 days. Clinical effects were judged from the changes in fever, cough, amount of sputum, dyspnea, rales, cyanosis, chest X-ray, white blood cell counts, CRP, erythrocyte sedimentation rates and results of sputum culture. Clinical effects were good in 16 subjects, fair in 1, and poor in 2. Bacteriological follow-up was carried out in 13 subjects. Infecting bacteria were eliminated from 5 subjects, reduced in 2 and, in 4 subjects, they were replaced by other bacteria. In 1 subject, P. aeruginosa was isolated from sputum even after the treatment with CPZ, and in another subject H. influenzae relapsed immediately after the cessation of the CPZ treatment.(ABSTRACT TRUNCATED AT 250 WORDS)