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Biomedical subjects

Michiaki Mishima

Publications and source records attributed to Michiaki Mishima.

At least 37 records · Page 2Linked to original sources

Matrix metalloproteinase-9 promoter polymorphism associated with upper lung dominant emphysema.

RATIONALE: Matrix metalloproteinase 9 (MMP-9) has proteolytic activity against connective tissue proteins and appears to play an important role in the development of chronic obstructive pulmonary disease (COPD). The functional polymorphism of MMP-9 (C-1562T) is considered as one of the candidate genes in the susceptibility to COPD. OBJECTIVES: To determine if MMP-9 (C-1562T) is related to the development of COPD in the Japanese population and whether it is associated with development of pulmonary emphysema assessed by high-resolution computed tomographic (HRCT) parameters. METHODS: MMP-9 (C-1562T) genotypes of 84 patients with COPD and 85 healthy smokers (control subjects) were determined by the restriction fragment length polymorphism method. We investigated the relationship between the genotypes using automatically analyzed HRCT parameters, such as percentage of low attenuation area (LAA%) and average computed tomography (CT) value density (Hounsfield units; mean CTv) in upper, middle, and lower lung fields in all patients with COPD. MEASUREMENTS AND MAIN RESULTS: There was no difference in polymorphism of MMP-9 (C-1562T) between patients with COPD and control subjects. In the HRCT study, patients with COPD with a T allele (C/T or T/T) showed larger LAA% (95% confidence interval of difference, 0.5-18.7; p = 0.04), and smaller mean CTv (confidence interval, -34.3 to -1.0; p = 0.04) in the upper lung compared with patients without T alleles (C/C). However, pulmonary function tests showed no difference between the two patient groups. Patients with a T allele showed a decrease in LAA% and an increase in mean CTv from upper to lower lung fields (p = 0.006 and p = 0.002, respectively). CONCLUSIONS: Polymorphism of MMP-9 (C-1562T) was associated with upper lung dominant emphysema in patients with COPD.

Aged↗

Noninvasive ventilation for pediatric patients including those under 1-year-old undergoing liver transplantation.

Pulmonary complications are an important cause of the mortality associated with liver transplantation. The efficacy of noninvasive ventilation (NIV) in pediatric patients following transplantation is unknown. The purpose of this retrospective study is to investigate the effects of NIV for pediatric patients undergoing liver transplantation. Of 102 pediatric patients who underwent liver transplantation, 15 patients (aged 73 months; range 2.5-179) were supported by NIV because of atelectasis, hypercapnia, hypoxemia, pneumonia, massive effusion, or postextubation ventilatory support. Of 15 patients, 5 were under the age of 1 year (range 2.5-12 months). Of the 15 patients, 7 had required multiple intubations before NIV treatment because of pulmonary complications. NIV treatment was administered to 6 patients because of hypercapnia. Partial pressure of arterial carbon dioxide (PaCO(2)) levels improved from 56.9 (95% confidence interval [CI]: 48.4-65.4) to 41.5 (95% CI: 36.8-46.2) mmHg (P = .028) within 2 days. NIV treatment was very effective for patients with atelectasis with and without other pulmonary complications. Mean inspiratory positive pressure (IPAP) was 7.2 (95% CI: 6.0-8.3) cm H(2)O and expiratory positive pressure (EPAP) was 3.5 (95% CI: 3.2-3.9) cm of H(2)O. Mean duration of NIV was 18.5 (95% CI: 8.6-28.4) days. IPAP and EPAP levels were closely and significantly correlated with height (IPAP: r = .65, P = .016; EPAP: r = .77, P = .004). A total of 13 patients recovered and 2 patients died. However, no patient died of respiratory complications. In conclusion, NIV is effective in pediatric patients undergoing liver transplantation with subsequent pulmonary complications. The IPAP and EPAP levels may be predicted by the height of the patient.

Adolescent↗

Living donor liver transplantation with noninvasive ventilation for exertional heat stroke and severe rhabdomyolysis.

A 16-year-old male with exertional heat stroke (EHS) had extensive hepatocellular damage, severe rhabdomyolysis, renal failure, and coma. Hemodiafiltration was started on day 2 and living donor liver transplantation was performed on day 3. He received continuous mechanical ventilation with intubation before and after the surgery. As his mental status improved, he could not tolerate intubation, and he was extubated on postoperative day (POD) 26. He received facial noninvasive positive pressure ventilation until POD 50. Hemodiafiltration was discontinued on POD 52. He was discharged on POD 67 and is currently well more than a year after transplantation. A literature search indicates that this patient is the first long-term survivor (>1 year) after liver transplantation for exertional heat stroke.

Adolescent↗

Longitudinal changes in patient vs. physician-based outcome measures did not significantly correlate in asthma.

BACKGROUND AND OBJECTIVE: Although improving health status is one important aim in managing asthmatic patients, few studies have evaluated their health status longitudinally. Therefore, we examined longitudinal changes in health status of asthma patients, and compared them with changes in physiological measures. METHODS: Eighty-seven outpatients with stable asthma after 6 months of treatment were recruited. Health status using the Asthma Quality of Life Questionnaire (AQLQ) and the St. George's Respiratory Questionnaire (SGRQ), pulmonary function, peak expiratory flow (PEF) values, and airway hyperresponsiveness (AHR) were evaluated at entry and every year over a 5-year period. RESULTS: Using mixed effects models to estimate the slopes, the overall AQLQ score declined statistically at a mean rate of 0.06 units/year (P=.0091). However, this decline did not reach a clinically significant level at 5 years. The total SGRQ score did not change significantly (P=.54). Although the forced expiratory volume in 1 sec declined at a mean rate of 53 mL/year, the PEF variability and AHR improved significantly. CONCLUSION: Health status was clinically stable over the 5-year study period in patients with asthma, which contrasted with the changes in the physiological outcome measures. As a patient centered outcome measure, health status should be followed separately.

Administration, Inhalation↗

Resistant hepatic hydrothorax: a successful case with treatment by nCPAP.

Hepatic hydrothorax is defined as pleural effusion with liver cirrhosis but no primary cardiopulmonary disease. Hepatic hydrothorax is often resistant to various therapeutic interventions. The most likely cause is the transfer of ascites fluid from the abdomen to the pleural space via the diaphragm because of a negative intrathoracic pressure gradient. A 62-year-old man was diagnosed with hepatoma and cirrhosis. After a partial hepatectomy, he suffered with hepatic hydrothorax. He had snoring without obvious sleep apnea. The patient's hepatic hydrothorax markedly improved following nasal continuous positive airway pressure (nCPAP) treatment during sleep. The mechanism for the improvement may have been the intrathoracic positive pressure during sleep induced by the nCPAP treatment during sleep. nCPAP treatment may provide a new therapy for resistant hepatic hydrothorax.

Carcinoma, Hepatocellular↗

Exercise capacity deterioration in patients with COPD: longitudinal evaluation over 5 years.

BACKGROUND: Although exercise capacity is an important outcome measure in patients with COPD, its longitudinal course has not been analyzed in comparison to the change in pulmonary function. PURPOSES: To examine how exercise capacity would deteriorate over time in patients with COPD, and what factors would contribute to it. METHODS: A total of 137 male outpatients with moderate-to-very-severe COPD were examined. The average age was 69.0 +/- 6.6 years (+/- SD), and the mean postbronchodilator FEV(1) was 45.9 +/- 15.4% predicted. Progressive cycle ergometry and pulmonary function testing were performed at entry, and every 6 months thereafter over 5 years. Due to the presence of missing data, a mixed-effect model analysis was then used to estimate the longitudinal changes in various clinical parameters. RESULTS: Peak oxygen uptake (Vo(2)), peak minute ventilation (Ve), and peak tidal volume (Vt) during exercise declined significantly over time (p < 0.0001), which was no less rapid than the deterioration in FEV(1). The mean decline rates for peak Vo(2) were 32 +/- 60 mL/min/yr and 0.5 +/- 1.0 mL/min/kg/yr. Multiple regression analysis revealed that the changes in peak Ve, peak Vt, and peak respiratory rates were significant predictors for the change in peak Vo(2). CONCLUSION: We demonstrated clear evidence of measurable and progressive deterioration in exercise capacity in COPD patients, which was no less rapid than the decline in airflow limitation. Dynamic ventilatory constraints during exercise also deteriorated over time, which most significantly contributed to this exercise capacity deterioration. In addition to pulmonary function, the longitudinal follow-up of exercise capacity is important not to miss the overall deterioration in COPD.

Aged↗

Multiple bone fractures found in a young sarcoidosis patient with long stable disease.

A 22-year-old Japanese man was found to have bilateral hilar lymphadenopathy (BHL), and was diagnosed with sarcoidosis in 1995. He was followed without treatment until 2002, when a bone fracture due to osseous sarcoidosis was found in his left thumb. Despite systemic treatment with corticosteroid and methotrexate, a new bone lesion developed in his right foot and his right middle finger was fractured. The patient also suffered multiple organ involvements including brain and muscle lesions. This is the first report of a sarcoidosis patient who presented with BHL, and developed bone fractures after a long stable period of more than 5 years.

Adult↗

Long-term clinical course of a patient with anti PL-12 antibody accompanied by interstitial pneumonia and severe pulmonary hypertension.

We report a case of a patient with anti PL-12 antibody accompanied by interstitial pneumonia and severe pulmonary hypertension. At first presentation, hyperkeratotic skin lesions were found, although the diagnosis of CVD was not conclusive. Lung histology showed diffuse fibrosing interstitial pneumonia predominantly in the subpleural regions. During the seven-year follow-up period, severe pulmonary hypertension developed, although the progression of lung fibrosis was relatively limited. Anti-PL12 antibody was detected, and therefore the patient was diagnosed as having antisynthetase syndrome. Lung histology and pulmonary arteriogram suggested that vascular involvement of the disease contributed to the development of severe pulmonary hypertension.

Adult↗

Patient characteristics and clinical features of Japanese sarcoidosis patients with low bronchoalveolar lavage CD4/CD8 ratios.

BACKGROUND: Previous studies have shown that there is an association between low BALF (bronchoalveolar lavage fluid) CD4/CD8 ratio and lower remission rates in sarcoidosis patients. AIM: To investigate the patient characteristics and clinical features of Japanese sarcoidosis patients with low BALF CD4/CD8 ratios. METHODS: 322 Japanese sarcoidosis patients were retrospectively analyzed, and 3 groups were selected according to BALF CD4/CD8 ratios as follows: patients with the BALF CD4/CD8 ratio in the lowest 5 percentile (Group 1: 0.43-1.41), median 5 percentile (Group II: 4.68-5.47), and top 5 percentile (Group III: 12.6-60.1). Each group consisted of 16 patients (5% of 322 patients). The patient characteristics, clinical features, and the short-term prognosis for at least 2 years (average 116 months) were compared among the groups. Multivariate analysis was performed for 322 patients to investigate the determinants of BALF CD4/CD8 ratios. RESULTS: The number of BALF CD8+ cells were greater in Group I than in the other two groups. In Group I, there were higher incidences of younger age, male gender, and lower number of extrathoracic lesions compared with Group III. Multivariate analysis showed that younger age and male gender were independently associated with low BALF CD4/CD8 ratios. The frequency of treatment with corticosteroid and progression to pulmonary fibrosis tended to be higher in Group I. CONCLUSIONS: Low BALF CD4/CD8 ratios were due to increased number of BALF CD8+ cells. Younger age and male gender were independently associated with low BALF CD4/CD8 ratios in sarcoidosis patients.

Adult↗

Pulmonary manifestations of primary Sjogren's syndrome: a clinical, radiologic, and pathologic study.

RATIONALE: Clinicopathologic pulmonary manifestations associated with primary Sjogren's syndrome have yet to be reviewed in a large series since the recognition of nonspecific interstitial pneumonia (NSIP) as a distinct histologic pattern. OBJECTIVES: To determine clinical presentations, high-resolution computed tomographic (HRCT) and histologic findings of the lung disease associated with primary Sjogren's syndrome in the light of NSIP, and to analyze prognosis of the disease. METHODS: On the basis of 33 cases (31 surgical lung biopsies and 2 autopsies) collected consecutively from multiple centers, we have retrospectively evaluated clinical, radiologic, and pathologic manifestations of the disease. Prognostic factors were identified by univariate and multivariate analysis. MEASUREMENTS AND MAIN RESULTS: We found that NSIP was the most frequently seen histologic pattern (20 of 33 cases [61%], 19 fibrosing and 1 cellular). Bronchiolar diseases and amyloid and malignant lymphoma were seen less frequently. HRCT-pathologic correlation resulted in a 94% positive predictive value of CT-NSIP pattern for pathologic diagnosis of NSIP, whereas the diagnostic value of HRCT was low (15%) with an HRCT pattern other than NSIP, data that may influence the decision to biopsy. The 5-year survival rate was 84% overall and 83% in patients with NSIP. Multivariate analysis on all patients showed that low Pa(O(2)) (p = 0.02) and presence of microscopic honeycombing (p = 0.04) were independently associated with survival. Patients with NSIP showed lower vital capacity (mean +/- SD: 68.5 +/- 16.6%pred) than patients without NSIP (92.5 +/- 18.6%pred; p < 0.001). CONCLUSION: Among a diversity of pulmonary lesions in primary Sjogren's syndrome, NSIP was the commonest histologic pattern and had a favorable prognosis.

Biopsy↗

Effect of short-term treatment with inhaled corticosteroid on airway wall thickening in asthma.

PURPOSE: Computed tomography studies demonstrate thickening of the asthmatic airway wall and its relation to disease severity. We evaluated the effect of inhaled corticosteroid on this phenomenon. METHODS: Cross-sectional images of the right upper lobe apical segmental bronchus were obtained by helical computed tomography in 45 corticosteroid-naïve patients with persistent asthma and 28 healthy controls. Airway wall thickness was measured as airway wall area normalized to body surface area. Computed tomography, pulmonary function, and serum levels of eosinophil cationic protein were examined before and after treatment with beclomethasone (800 microg/d for 12 weeks). RESULTS: Before treatment, airway wall thickness was greater in asthma patients than in controls (P <0.0001). After treatment, it decreased by 11% (P <0.001) but remained high (P <0.0001 vs. control); the serum level of eosinophil cationic protein decreased, and airflow obstruction was reduced, but not to the level in controls. The decrease in wall thickness was associated with a decrease in the serum level of eosinophil cationic protein (r = 0.39, P = 0.009) and an increase in the forced expiratory volume in 1 second (r = 0.45, P = 0.003) and was inversely related to disease duration at entry (r = -0.38, P = 0.009). Post-treatment wall thickness was related to disease duration (r = 0.45, P = 0.003) and remaining airflow obstruction. CONCLUSION: Wall thickening of asthmatic central airways responds partially to inhaled corticosteroid therapy and may reflect an overall reduction in airway inflammation. "Unresponsive components," possibly involving structural changes, may increase in the absence of inhaled corticosteroid treatment, potentially leading to chronic airflow obstruction.

Administration, Inhalation↗

Response shift in perception of sleepiness in obstructive sleep apnea-hypopnea syndrome before and after treatment with nasal CPAP.

STUDY OBJECTIVES: After nasal continuous positive airway pressure (nCPAP) treatment, several symptoms such as hypersomnolence, daytime fatigue, and impaired concentration improve in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). A variability of perception of pretreatment sleepiness (response-shift phenomenon) experienced in OSAHS patients before and after nCPAP treatment may reflect informative shifts in an individual's internal standards, in values and priorities, or in the conceptualization of perceived sleepiness. The objective of this study is to determine whether there is a response shift in perceptions of pretreatment sleepiness before and after nCPAP treatment in patients with OSAHS. We investigated the response shift in Epworth Sleepiness Scale scores before and after nCPAP. DESIGN: Thirty-one consecutive OSAHS patients filled out the subjective ESS before nCPAP treatment (Pre-ESS). After a mean of about 10 months of nCPAP treatment, the patients filled out the ESS again, which was designated as the Post-ESS. Then they were asked to complete the scale again, recalling sleepiness before nCPAP treatment (Response Shift-Pre-ESS). The control group consisted of 11 patients with OSAHS who had not yet received nCPAP treatments and were matched for age, body mass index, and respiratory disturbance index. SETTING: University Hospital in, Japan. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: There was a significant response shift in ESS scores before and after nCPAP treatment (Pre-ESS: 8.5 [95% Confidence interval [CI], 7.1-9.9] vs Response Shift-Pre-ESS: 11.1 [95% CI, 9.5-12.8], P < .002). A significant number of patients (P < .02) had not recognized the degree of sleepiness experienced before treatment until after they had received nCPAP treatment. Eight had pretreatment ESS scores > or = 11 and 18 had posttreatment ESS scores > or = 11 on the Response Shift-Pre-ESS. In the control group, ESS did not change significantly from the first to the second testing performed before nCPAP treatment (first ESS, 8.8 [95% CI, 5.3-12.3]; second ESS, 8.3 [95% CI, 4.7-11.8]: P = .95). CONCLUSIONS: Response shifts should be taken into consideration when explaining factors underlying individual differences in susceptibility to daytime sleepiness.

Arousal↗

The plasminogen activation system reduces fibrosis in the lung by a hepatocyte growth factor-dependent mechanism.

Mice deficient in the plasminogen activator inhibitor-1 gene (PAI-1-/- mice) are relatively protected from developing pulmonary fibrosis from bleomycin administration. We hypothesized that one of the protective mechanisms may be the ability of the plasminogen system to enhance hepatocyte growth factor (HGF) effects, which have been reported to be anti-fibrotic in the lung. HGF is known to be sequestered in tissues by binding to extracellular matrix components. Following bleomycin administration, we found that HGF protein levels were higher in bronchoalveolar lavage fluid from PAI-1-/- mice compared to wild-type (PAI-1+/+) mice. This increase could be suppressed by administering tranexamic acid, which inhibits plasmin activity. Conversely, intratracheal instillation of urokinase into bleomycin-injured PAI-1+/+ mice to activate plasminogen caused a significant increase in HGF within bronchoalveolar lavage and caused less collagen accumulation in the lungs. Administration of an anti-HGF neutralizing antibody markedly increased collagen accumulation in the lungs of bleomycin-injured PAI-1-/- mice. These results support the hypothesis that increasing the availability of HGF, possibly by enhancing its release from extracellular matrix by a plasmin-dependent mechanism, is an important means by which activation of the plasminogen system can limit pulmonary fibrosis.

Animals↗

Possible maximal change in the SF-36 of outpatients with chronic obstructive pulmonary disease and asthma.

The purpose of the present study was to investigate the responsiveness of the Short Form-36 (SF-36) in patients with chronic obstructive pulmonary disease (COPD) and asthma. We studied patients with COPD and asthma who attended our outpatient clinic. In the first cross-sectional study, we compared the differences in the SF-36 scores between pretreatment patients (152 with COPD and 174 with asthma) who visited the clinic for the first time and in-treatment patients (123 with COPD and 151 with asthma) who had received treatment for > 6 months. The differences in each scale of the SF-36 ranged from 6.9 to 14.4 in COPD patients and from 7.0 to 28.3 in asthma patients. In the second longitudinal study, patients who visited for the first time were enrolled, and the initial, and, 3-, 6-, and 12-month evaluations of the SF-36 were studied. A total of 136 COPD patients and 136 asthma patients were enrolled consecutively, and 100 patients with COPD and 66 patients with asthma completed the year-long examinations. In COPD patients, except for bodily pain, the scores in all scales of the SF-36 improved significantly during the first 3 or 6 months. In patients with asthma, all scale scores of the SF-36 improved significantly during the first 3 months. Maximal changes in the SF-36 scores were observed at 6 or 12 months. Longitudinal maximal changes in each scale approached or exceeded the possible maximal changes, which were derived from the differences in the scores between pretreatment patients and in-treatment patients in the first cross-sectional study. Improvements in the SF-36 scores showed moderate to strong negative correlations with their baseline scores in patients with COPD and asthma. In conclusion, the SF-36 shows sufficient responsiveness in the assessment of the health status of patients with COPD and asthma, but these responses are strongly influenced by their baseline values.

Administration, Inhalation↗