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Biomedical subjects

Michiaki Mishima

Publications and source records attributed to Michiaki Mishima.

At least 55 records · Page 3Linked to original sources
PubMed2004

Risk and severity of COPD is associated with the group-specific component of serum globulin 1F allele.

BACKGROUND: The finding that only 15 to 20% of cigarette smokers acquire COPD suggests that there is a genetic predisposition to the disease. Genetic polymorphism of the group-specific component of serum globulin (Gc-globulin), also known as vitamin-D-binding protein, is considered one of the candidates for the susceptibility to COPD. However, the role of Gc-globulin polymorphism in the development of COPD remains inconclusive. STUDY OBJECTIVE: s: To determine whether Gc-globulin gene polymorphism plays a role in the development of COPD in the Japanese population, and whether it is associated with the physiologic deterioration in COPD, and its radiologically detectable correlates. DESIGN: Association study. SUBJECTS AND METHODS: One hundred three patients with COPD and 88 healthy smokers sampled from the Japanese population were genotyped for Gc-globulin by the restriction fragment-length polymorphism method. Based on the results of the genotyping, we investigated the relationship between Gc-globulin polymorphism and a physiologic/radiologic indicator of lung function, namely, the annual decline of FEV(1) (dFEV(1)) in 86 patients with COPD and 21 healthy smokers. Additionally, high-resolution CT parameters such as low-attenuation area percentage (LAA%) and average CT number (mean CT score) were measured in 85 patients with COPD. RESULTS: There was an increased proportion of Gc*1F homozygotes in the patients with COPD (32%) compared with the healthy smokers (17%) [p = 0.01; odds ratio, 2.3; 95% confidence interval, 1.2 to 4.6]. Patients with COPD and the Gc*1F allele showed a larger dFEV(1) (p = 0.01), higher frequency with LAA% > 60% (p = 0.01), and lower mean CT score than patients without this allele (p = 0.03). CONCLUSION: Gc-globulin polymorphism is significantly associated with susceptibility to COPD, and also with the severity of the disease.

Aged↗
PubMed2004

Bronchial dilatation in asthma: relation to clinical and sputum indices.

BACKGROUND: Investigations using high-resolution CT (HRCT) show that bronchial dilatation (BD) is found in many patients with asthma. However, the pathogenesis and pathophysiologic relevance of BD in asthma are poorly understood. A balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may control the remodeling of extracellular matrix, and excess MMPs have been associated with destruction or dilatation of airways in patients with bronchiectasis. OBJECTIVES: To study the prevalence of BD as assessed by HRCT according to standard subjective criteria in 37 patients with stable asthma and 10 healthy control subjects, and to examine the relation of BD in asthmatic patients to clinical characteristics and sputum indices, including MMP-9 and TIMP-1 levels. DESIGN: A prospective cohort study. RESULTS: At least one dilated bronchus was present in 23 asthmatic subjects (62%) and 2 control subjects (20%) [p = 0.030]. The ratio of dilated bronchi to all eligible bronchi in each subject (individual BD%) was higher in the asthmatic patients than in the control subjects (11.4 +/- 16.1% vs 1.3 +/- 3.0%, p = 0.011) [mean +/- SD]. Asthmatic patients with (n = 23) and those without BD (n = 14) were similar with regard to age, duration and severity of asthma, atopy, pulmonary function, sputum eosinophil or neutrophil count, and sputum levels of MMP-9 or TIMP-1 and their molar ratio. Individual BD% of asthmatic patients was also unrelated to these clinical and sputum variables. When analysis was confined to the 23 patients with BD, however, individual BD% correlated with the severity score of asthma (r = 0.49, p = 0.023). The results of follow-up HRCT obtained from 19 patients suggested that BD was a fixed rather than transient phenomenon. CONCLUSION: BD is more prevalent in asthmatic patients than in normal subjects and might be associated with the severity of asthma. Cellular inflammation or possible imbalance between MMP-9 and TIMP-1 was not demonstrated in this study to be related to BD in asthma.

Asthma↗
PubMed2004

Corrected QT dispersion and cardiac sympathetic function in patients with obstructive sleep apnea-hypopnea syndrome.

STUDY OBJECTIVES: Hypoxemia increases corrected QT dispersion (QTcD), which is the difference between the maximum and minimum QT intervals and is a strong risk factor for cardiovascular mortality. The aim of this study was to investigate the QTcD in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS), and the relationship between the QTcD and (123)I-metaiodobenzylguanidine (MIBG) cardiac imaging, which reflects cardiac sympathetic activity. SETTING: A university hospital. PATIENTS: Forty-eight OSAHS patients without cardiac diseases (mean [+/- SD] age, 45.9 +/- 10.8 years; apnea-hypopnea index [AHI] 51.9 +/- 18.5 events per hour) who underwent polysomnography before treatment and on the first night of nasal continuous positive airway pressure (nCPAP) treatment. METHODS: Before and after nCPAP treatment was started, we measured the QTcD with computer software, before, during, and after sleep, as well as the washout rate of the MIBG administered for cardiac imaging. As a control, QTcD was also measured in the morning from 26 healthy subjects. RESULTS: Before treatment, the mean QTcD during sleep (65.0 +/- 14.6 ms) was greater than that before sleep (57.0 +/- 13.5 ms; p < 0.0001). Meanwhile, after 1 night of nCPAP therapy, the QTcD during sleep (50.6 +/- 11.4 ms) decreased from that before treatment (p < 0.0001) and was smaller than the QTcD before sleep (56.2 +/- 13.3 ms; p = 0.003). Before treatment, the QTcD during sleep correlated with the AHI (r = 0.38; p = 0.009) and the percentage of time that SaO(2) was < 90% (SaO(2) < 90% time) [r = 0.34; p = 0.018]. The QTcD did not correlate with the body mass index or the washout rate of MIBG. However, the washout rate of MIBG correlated with the AHI and the SaO(2) < 90% time. CONCLUSIONS: Nocturnal QTcD is increased in OSAHS patients but is decreased by nCPAP therapy independently of cardiac sympathetic function.

3-Iodobenzylguanidine↗
PubMed2004

Clinical assessment of airway remodeling in asthma: utility of computed tomography.

Airway remodeling is an established feature of asthma. Histologic examination is essential in the assessment of remodeling that is a pathologic concept. Examinations of autopsied or resected lung have enabled detailed morphologic and morphometric studies and have provided fundamental knowledge of airway remodeling in asthma. However, such materials are only accidentally available, and clinical information may often be insufficient in autopsied cases. Bronchoscopic mucosal biopsy has been widely used since the 1980s, and has contributed substantially to basic investigations of inflammation and remodeling. However such specimens are limited in size and depth, limited to central airways, and the procedure might be too invasive to be repeated. Remodeling can also be assessed indirectly. Pulmonary function tests to evaluate chronic airflow obstruction are available in clinical settings and suitable for screening or mass studies, but they may be affected by concomitant diseases or short-term asthma control. Computed tomography (CT) has recently been utilized to assess remodeling. It cannot discern pathologic details but provides a broader range of airway/lung morphology and may be less invasive compared to biopsy. In addition to classic subjective evaluations,quantitative assessment has been reported for central airway dimensions, such as airway wall area, luminal area and wall thickness, and for peripheral airway abnormality or air trapping as measured by decreased lung attenuation or increased mosaic perfusion. This article summarizes the merits and limitations of various methods to assess airway remodeling, and describes the details of methodologies, interpretations, pathophysiologic relevance, and future directions of asthmatic airway remodeling assessed by CT.

Adult↗
PubMed2004

Successful weaning using noninvasive positive pressure ventilation in a patient with status asthmaticus.

In the treatment of severe asthma attack, acute application of non-invasive positive pressure ventilation is shown to be beneficial in some selected patients, while endotracheal intubation and mechanical ventilation is required in the remaining cases. Management with invasive ventilation in status asthmaticus is often associated with complications such as excessive mucus production and atelectasis, which may lead to prolonged hypoxemia and may increase mortality. We present a case of status asthmaticus who developed refractory atelectasis during invasive mechanical ventilation but had a dramatic resolution as well as successful weaning when non-invasive positive pressure ventilation was instituted.

Adult↗
PubMed2004

Diabetes insipidus from neurosarcoidosis: long-term follow-up for more than eight years.

Four patients with sarcoidosis presented as hypothalamic-hypophyseal syndrome including diabetes insipidus (DI) were followed up for more than 8 years from the onset of clinical manifestation. The mean age was 26 years, male : female ratio was 3 : 1 and the mean disease duration of 10 years. All patients had hypogonadism, hyperprolactinemia. Pituitary enlargement with thickening of the pituitary stalk were detected by magnetic resonance imaging (MRI) with gadolinium enhancement and attenuation in the intensity of the posterior lobe of the pituitary was detected without enhancement. Corticosteroid therapy resulted in the initial improvement of symptoms and gradual decrease in the tumor size but failed to cure polyuria due to DI. The use of desmopressin was necessary for a long period. None of these patients died from DI or central neurosarcoidosis.

Adrenal Cortex Hormones↗
PubMed2003

Relationship of airway wall thickness to airway sensitivity and airway reactivity in asthma.

Airway wall thickening has been assumed to cause airway hyperresponsiveness, but a protective effect against airway narrowing has also been suggested. We investigated the relationship between airway wall thickness as assessed by helical computed tomography and two components of airway responsiveness, airway sensitivity and reactivity, in patients with stable asthma with (n = 23) and without (n = 22) inhaled steroid treatment. A cross-section of the apical bronchus of the right upper lobe was obtained. Airway wall area corrected by body surface area was measured as an index of wall thickness. Airway sensitivity and reactivity were measured by continuous inhalation of methacholine, on the basis of the methacholine respiratory resistance dose-response curve. The eosinophil count in sputum was determined in 16 patients [steroid (+) group] and 14 patients [steroid (-) group]. In both groups of patients, airway sensitivity was not related to airway reactivity. Airway sensitivity was related to eosinophil count [r = 0.57 in the steroid (+) group and r = 0.49 in the steroid (-) group], but not to airway wall thickness. In contrast, airway reactivity negatively correlated with airway wall thickness [r = -0.56 in the steroid (+) group and r = -0.55 in the steroid (-) group] but not with eosinophil count. Our results suggest that airway wall thickening attenuates airway reactivity in patients with asthma. These findings may have important implications in pathophysiology and in the treatment of airway remodeling.

Adrenergic beta-Agonists↗
PubMed2003

Effects of obstructive sleep apnea syndrome on serum aminotransferase levels in obese patients.

PURPOSE: Obesity has been associated with obstructive sleep apnea and hepatic steatosis. We investigated the effects of obstructive sleep apnea and treatment with nasal continuous positive airway pressure (CPAP) on serum aminotransferase levels in obese patients. METHODS: We studied 40 obese men with obstructive sleep apnea syndrome. None had hepatitis B antigen or C antibody, autoimmune disease, or an excessive intake of alcohol. Serum levels of aspartate aminotransferase, alanine aminotransferase, triglyceride, glucose, insulin, and leptin were determined in the afternoon and in the morning immediately after sleep, before and after nasal CPAP treatment. RESULTS: Aminotransferase levels were abnormal in 35% (n = 14) of patients. Before treatment, mean (+/- SD) aspartate aminotransferase levels were higher in the morning than in the previous afternoon (presleep, 34 +/- 20 IU/L; postsleep, 39 +/- 28 IU/L; P = 0.006). The overnight mean increases in aminotransferase levels were less marked after the first night of nasal CPAP treatment (aspartate aminotransferase: from 6 +/- 11 IU/L to 2 +/- 6 IU/L, P = 0.0003; alanine aminotransferase: from 5 +/- 9 IU/L to 2 +/- 6 IU/L, P = 0.006). Leptin levels (n = 23) decreased significantly after treatment (P = 0.0002), whereas insulin resistance (calculated by the homeostasis model assessment method) and triglyceride levels were unchanged. Improvements in aspartate and alanine aminotransferase levels were maintained after 1 and 6 months of nasal CPAP treatment. CONCLUSION: Nasal CPAP therapy may have beneficial effects on serum aminotransferase abnormalities in obese patients who have obstructive sleep apnea.

Alanine Transaminase↗
PubMed2003

Complexity of terminal airspace geometry assessed by computed tomography in asthma.

Low attenuation areas in computed tomography images from patients with chronic obstructive pulmonary disease have been reported to represent macroscopic and/or microscopic emphysema. The cumulative size distribution of the clusters has been shown to follow a power law characterized by the exponent D, a measure of the complexity of the terminal airspace geometry. We have previously found increased low attenuation areas in nonsmoking subjects with asthma. We examined the size distribution of the clusters in nonsmoking subjects with asthma compared with both nonsmoking control subjects and subjects with asthma with a smoking history. The percentage of lung field occupied by low attenuation areas (LAA%) and D in subjects with asthma with a smoking history differed significantly from nonsmoking subjects with asthma and control subjects. In nonsmoking subjects with asthma, both parameters differed significantly between severe asthma and mild or moderate asthma. The LAA% differed significantly between moderate and mild asthma, but D did not. In mild and moderate asthma, a highly significant correlation between LAA% and D was observed in patients with a smoking history, but not in nonsmoking subjects with asthma. Our results suggest that decreased D is mostly related to emphysematous change, and both measurements of LAA% and D may provide useful information to characterize low attenuation areas in subjects with asthma.

Aged↗
PubMed2003

A comparison of the responsiveness of different generic health status measures in patients with asthma.

Generic health status has been recommended to be measured separately from disease-specific health status, because they can yield complementary information. In particular, generic health status can provide comprehensive health ratings across various disorders. However, the weakness with generic measures is that they may be less responsive to clinical changes than disease-specific ones. Therefore, when using generic health status as an endpoint in clinical trials, the instrument to be used is a problem with respect to responsiveness. In the present study, we investigated and compared the responsiveness of health status measures during asthma treatment using three different generic instruments: the Medical Outcomes Study Short Form 36-items Health Survey (SF-36), the Nottingham Health Profile (NHP) and the EQ5D (EuroQoL), as well as one disease-specific instrument, the Asthma Quality of Life Questionnaire (AQLQ). Fifty-four new patients with asthma who consulted our clinic were recruited. The health status measurements were performed on the initial visit, and at 3 and 6 months. All subscales of the SF-36 showed a significant improvement during the first 6 months. Each dimension of the EQ5D showed stronger ceiling effects than the SF-36. With respect to the responsiveness indices, the SF-36 was regarded as more responsive than the NHP or EQ5D utility. The changes in the SF-36 had a weak to moderate correlation with the changes in the AQLQ. In conclusion, the SF-36 had a higher responsiveness for asthma as a generic measure than the NHP or EQ5D, and evaluated different aspects from the AQLQ. The SF-36 can be used effectively in asthma clinical trials.

Asthma↗
PubMed2003

A comparison of the effects of salbutamol and ipratropium bromide on exercise endurance in patients with COPD.

STUDY OBJECTIVE: Inhaled bronchodilators are the first-line pharmacotherapy against COPD. The purpose of the present study was to investigate the effects of beta(2)-agonists and anticholinergic agents on the exercise capacity of patients with COPD. METHODS: A total of 67 stable patients with COPD were recruited at the Kyoto University Hospital. After inhaling 400 micro g salbutamol, 80 micro g ipratropium bromide, or an identical placebo in a randomized, double-blind, crossover fashion, the patients performed cycle endurance tests at a constant workload of 80% of the maximum work rate reached on progressive cycle ergometry, and the endurance time was recorded. RESULTS: Both salbutamol and ipratropium bromide significantly improved the endurance time by 29 s (15%; p < 0.001) and 27 s (14%; p < 0.001), respectively, in comparison with the placebo. However, there was no statistically significant difference between them (p = 0.71). The dyspnea ratios were also similarly reduced by both bronchodilators. The difference in the endurance time between therapy with salbutamol and placebo was significantly, but moderately, related to the difference between therapy with ipratropium bromide and placebo. In addition, there were no relationships, or only weakly significant relationships, between the change in FEV(1) and the change in the endurance time, the highest oxygen uptake, and the highest minute ventilation for both salbutamol and ipratropium bromide. CONCLUSIONS: Therapy with both salbutamol and ipratropium bromide improved exercise capacity, as evaluated by the endurance time, and reduced dyspnea similarly in patients with COPD. In addition, the effects of the different bronchodilators on exercise capacity varied within individuals, and a complex mechanism may be responsible for the different effects of these two bronchodilators on exercise capacity vs airflow limitation. These results support the conclusion that both types of inhaled bronchodilators can be used as first-line drugs for the treatment of stable patients with COPD.

Adrenergic beta-Agonists↗
PubMed2003

Optimal cutoff level of breath carbon monoxide for assessing smoking status in patients with asthma and COPD.

STUDY OBJECTIVES: To assess the optimal cutoff level of breath CO concentration to distinguish actual smokers from nonsmokers among patients with asthma and COPD. SETTING: Kyoto University Hospital outpatient clinic. SUBJECTS AND METHODS: Three hundred thirty-one consecutive outpatients (161 with asthma and 170 with COPD) were examined cross-sectionally by self-reported smoking status, breath CO monitoring, and serum cotinine concentration. Actual smoking status was verified by serum cotinine concentration. RESULTS: Mean serum cotinine concentrations of never smokers, former smokers, and current smokers with asthma were 6.0 +/- 5.2 ng/mL, 12.1 +/- 25.0 ng/mL, and 198.3 +/- 181.7 ng/mL, respectively (+/- SD). Mean serum cotinine concentrations of former smokers and current smokers with COPD were 23.2 +/- 69.2 ng/mL and 191.1 +/- 109.8 ng/mL, respectively. Mean breath CO levels of never smokers, former smokers, and current smokers with asthma were 6.1 +/- 2.4 ppm, 7.7 +/- 3.2 ppm, and 19.9 +/- 17.3 ppm, respectively. Mean breath CO levels of former smokers and current smokers with COPD were 7.7 +/- 4.3 ppm and 13.5 +/- 6.5 ppm, respectively. The optimal cutoff level of breath CO to discriminate between actual smokers and nonsmokers was 10 ppm in patients with asthma and 11 ppm in patients with COPD, giving 85.0% and 73.1% sensitivity, and 85.8% and 84.7% specificity, respectively. CONCLUSION: The optimal cutoff level of breath CO to assess actual smoking status was 10 ppm in patients with stable asthma and 11 ppm in patients with stable COPD. In patients with asthma and COPD, breath CO levels were potentially influenced by underlying airway inflammation, suggesting misclassification in the assessment of smoking status by breath CO.

Adolescent↗
PubMed2003

Cyclophosphamide-induced late-onset lung disease.

We report the case of a 58-year-old woman who was considered to have died of cyclophosphamide (CPA)-induced late-onset lung disease. She underwent a right-sided mastectomy due to breast cancer at the age of 50 followed by daily administration of 50 mg CPA and 20 mg tamoxifen for 2 years. A refractory cough and dyspnea began at the age of 56. Chest radiographs revealed diffuse infiltrates and pleural thickening. Her vital capacity was markedly reduced. Corticosteroid therapy was ineffective. The disease rapidly progressed with occasional episodes of pneumothoraces to her death. Postmortem examination revealed pulmonary fibrosis with marked elastosis.

Aged↗
PubMed2003

Sarcoidosis with bilateral epididymal and testicular lesions.

We report a case of genital sarcoidosis that presented characteristic features on MRI. A 25-year-old man sarcoidosis patient with ocular and lung lesions presented a painful mass in the left scrotum together with systemic symptoms of fever, appetite loss, headache, and stomach-ache during the tapering of steroids. The patient was hypercalcemic, and this was thought to be the cause of his systemic symptoms. MRI showed multiple nodules of bilateral testes and enlargement of bilateral epididymis; the patient was diagnosed with testicular and epididymal lesions of sarcoidosis. An increased steroid dosage improved his hypercalcemia and genital lesions.

Adult↗
PubMed2003

Sarcoidosis complicated with IgA nephropathy.

Though IgA nephropathy (IgAN) and sarcoidosis have been reported simultaneously in patients occasionally, it remains controversial whether there is any association between the two. In this report we describe our experience with one definite and two subclinical cases of IgAN diagnosed during the clinical course of sarcoidosis. Our findings suggest a possible association between these disorders, and a higher incidence of subclinical IgAN among sarcoidosis patients than among the general population. We also discuss the common immunological background shared by these two diseases.

Diagnosis, Differential↗
PubMed2003

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) exon 1 polymorphism affects lymphocyte profiles in bronchoalveolar lavage of patients with sarcoidosis.

BACKGROUND: Sarcoidosis is a systemic disease characterized by T-cell activation and subsequent granuloma formation at the site of involvement. Genetic susceptibility is a key factor in the pathogenesis of this disease, and genes involved in T-cell regulation are potential candidates. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a negative regulator of T-cell activation expressed on activated T-cells. The G allele of the CTLA-4 exon 1 polymorphism has previously been described to be associated with disease susceptibility in several autoimmune diseases. We investigated the relationship of CTLA-4 to disease susceptibility and cell profiles in bronchoalveolar lavage (BAL) in Japanese sarcoidosis patients. METHODS: Japanese sarcoidosis patients (n = 135) and controls (n = 97) were typed for an A/G bi-allelic polymorphism in exon 1 of CTLA-4 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the distribution of genotypes was compared between both groups. Sixty-seven patients underwent BAL, and cell profiles in BAL fluid were compared between patients with G/G genotype and those with A/A genotype. RESULTS: No significant differences in the distribution of genotype and allele frequencies were found between sarcoidosis (GG: 46%, AG: 39%, AA: 15%) and controls (GG: 42%, AG: 49%, AA: 8%). Patients with G/G genotype had significantly increased lymphocyte ratios, lymphocyte counts, and CD4(+) cell counts in BAL fluid compared with patients with A/A genotype (p < 0.05). CONCLUSIONS: CTLA-4 exonl polymorphism might affect BAL fluid lymphocyte profiles in Japanese sarcoidosis patients.

Adult↗