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Biomedical subjects

Masaki Fujimura

Publications and source records attributed to Masaki Fujimura.

At least 37 records · Page 2Linked to original sources
PubMed2005

Change in bronchial responsiveness and cough reflex sensitivity in patients with cough variant asthma: effect of inhaled corticosteroids.

BACKGROUND: Cough variant asthma (CVA) is a cause of chronic cough and a precursor of typical asthma. We retrospectively examined the longitudinal change in bronchial responsiveness and cough reflex sensitivity in CVA patients with respect to the effect of long-term inhaled corticosteroids (ICS). METHODS: Provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20-FEV1) and provocative concentration of capsaicin eliciting 5 or more coughs (C5) were measured before treatment and during a follow up period following relief of cough (median; 2.0 (range; 0.5 to 8.0) years after the initial visit) in a total of 20 patients with CVA (7 males and 13 females, mean +/- SD age of 49.9 +/- 12.9 years). RESULTS: Three of 8 patients not taking long-term ICS developed typical asthma compared to none of 12 patients taking ICS (p = 0.0171). PC20-FEV1 significantly (p < 0.0001) increased from 1.80 (GSEM, 1.35) to 10.7 (GSEM, 1.63) mg/ml in patients taking ICS but did not change in patients not taking ICS [2.10 (GSEM, 1.47) compared to 2.13 (GSEM, 1.52) mg/ml]. Cough threshold did not change in patients whether taking or not taking ICS. CONCLUSION: Long-term ICS reduces bronchial hyperresponsiveness in CVA as recognized in typical asthma. Cough reflex sensitivity is not involved in the mechanism of cough in CVA.

Journal Article↗
PubMed2005

Changes in angiogenic growth factor levels after gefitinib treatment in non-small cell lung cancer.

BACKGROUND: To investigate the changes in angiogenic growth factor expression before and after gefitinib treatment, and the association between this expression and response to gefitinib treatment, we measured circulating levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), matrix metalloproteinase (MMP) -2 and -9, and tissue inhibitors of metalloproteinase (TIMP) -1 and -2 in patients with non-small cell lung cancer (NSCLC). METHODS: Serum and plasma samples were collected from 52 patients before and after gefitinib treatment. The levels of VEGF, bFGF, MMP-2, MMP-9, TIMP-1 and TIMP-2 were measured using a sandwich enzyme immunoassay kit. RESULTS: Of the 52 patients, 17 (32.7%) achieved a partial response, 19 (36.5%) had stable disease and 16 (30.8%) had progressive disease. The levels of VEGF, bFGF, MMP-2, MMP-9, TIMP-1 and TIMP-2 did not change significantly after gefitinib treatment, even in responders. The levels of VEGF in volunteers, responders and non-responders were 384 +/- 86.4, 404 +/- 94.3 and 719 +/- 99.8 pg/ml, respectively. The difference between volunteers and responders was not significant (P = 0.540), while the differences between volunteers and non-responders (P = 0.031), and responders and non-responders (P = 0.028) were significant. CONCLUSIONS: Although our results indicate that gefitinib treatment does not affect circulating levels of angiogenic growth factors even in patients who showed a response to gefitinib treatment, low levels of VEGF may predict response to gefitinib treatment in patients with NSCLC.

Adult↗
PubMed2005

Granulocyte colony-stimulating factor-producing malignant pleural mesothelioma with the expression of other cytokines.

We report a 65-year-old man with malignant pleural mesothelioma that produced granulocyte colony-stimulating factor (G-CSF) and other cytokines. At the first presentation, the WBC count was 8600 cells/microl and C-reactive protein (CRP) was 0.6 mg/dl. Seventeen months later, the WBC count had increased to 53,600 cells/microl (93% neutrophils) and CRP to 27.1 mg/dl. The serum concentration of G-CSF had increased to 36.0 pg/dl (normal range, <5.0 pg/dl), interleukin 1beta (IL-1beta) to 46.0 pg/dl (normal range, <10 pg/dl), and IL-6 to 197 pg/dl (normal range, <4.0 pg/dl). The patient died 19 months after the first presentation, and 6 weeks after sudden leukocytosis. At autopsy, a diagnosis of malignant pleural mesothelioma was made. The tumor cells were positive for anti-human G-CSF, granulocyte-macrophage colony-stimulating factor, IL-1beta, and IL-6 antibodies. Malignant mesothelioma may produce G-CSF and other cytokines. Mesothelial cells may have the potential to produce G-CSF and other cytokines in the progress of malignant formation, and this may be a factor influencing the poor prognosis.

Aged↗
PubMed2005

IgG4-positive plasma cells in inflammatory pseudotumor (plasma cell granuloma) of the lung.

The association between IgG4 dysregulation and inflammatory pseudotumor (IPT) was first reported in sclerosing pancreatitis. Recently, we described IPTs of the liver and breast, into both of which many IgG4-positive plasma cells had infiltrated. In this study, we examined the clinical and histological features of 9 cases of IPT (histologically corresponding to plasma cell granuloma) of the lung with an emphasis on IgG4-positive plasma cell infiltration. The lesions were characterized histologically by dense lymphoplasmacytic infiltrates intermixed with fibrosis and, in some cases, prominent eosinophilic infiltration, irregular narrowing of bronchioles entrapped in nodules, and an interstitial pneumonia pattern at the boundaries of nodules. Obliterative phlebitis was easily found in all cases, and 5 lesions also had obliterative arteritis. Immunostaining revealed many IgG4-positive plasma cells diffusely distributed within nodules, and the ratios of IgG4-positive to other plasma cells were extraordinarily high. Of the 9 patients, 8 underwent surgical treatment and in 1 patient, lesion was diagnosed on transbronchial biopsy and effectively treated with corticosteroid. Two cases were associated with chronic sclerosing sialadenitis or lymphadenopathy, in which many IgG4-positive plasma cells were also identified by immunostaining. The clinicopathologic similarities between IPT of the lung and sclerosing pancreatitis suggest that IgG4-related immunopathologic processes might be involved in the pathogenesis of the pulmonary lesions.

Adult↗
PubMed2005

In vivo PAF-induced airway eosinophil accumulation reduces bronchial responsiveness to inhaled histamine.

Chronic eosinophilic bronchitis and bronchial hyperresponsiveness have been considered to be the fundamental features of bronchial asthma. However, the role of airway eosinophils in bronchial responsiveness in vivo has not been fully discussed. The aim of this study was to investigate the direct effect of airway eosinophil accumulation on bronchial responsiveness in vivo. Guinea pigs were transnasally treated with platelet activating factor (PAF) or vehicle twice a week for a total of 3 weeks. Anesthetized guinea pigs were surgically cannulated and artificially ventilated 48 h after the last administration of PAF or vehicle. Ten minutes after the installation of artificial ventilation, ascending doses of histamine were inhaled. In a subsequent study, selective inhibitors of diamine oxidase and histamine N-methyltransferase were intravenously administered before the histamine inhalation in the PAF-treated animals. Next study was conducted 20 min after treatment with indomethacin in this study line. Finally, ascending doses of methacholine were inhaled in our animal model. Proportion of eosinophils and the number of nuclear segmentation in bronchoalveolar lavage fluid significantly increased in guinea pigs treated with PAF compared with vehicle and this finding was confirmed histologically. Nevertheless, bronchial responsiveness to inhaled histamine, but not methacholine, was significantly decreased by the PAF treatment. This bronchoprotective effect induced by PAF remained following aminoguanidine and histamine N-methyltransferase administration, but abolished by treatment of indomethacin. These results suggest that in vivo airway eosinophils may reduce nonspecific bronchial responsiveness through production of inhibitory or bronchoprotective prostanoids, but not through histaminase production.

Administration, Inhalation↗
PubMed2005

Pulmonary hypertension after splenectomy in hereditary stomatocytosis.

Hereditary stomatocytosis is an autosomal dominant, congenital hemolytic form of anemia, and thromboembolic complications may ensue after a splenectomy is performed in a patient with hereditary stomatocytosis. However, little is known about the relationship between pulmonary hypertension and hereditary stomatocytosis. We describe here a rare case of a patient with hereditary stomatocytosis who developed pulmonary hypertension due to thromboembolic disease after splenectomy. At the first presentation, he was diagnosed with hemolytic anemia, but the cause was unknown, and he was also diagnosed with pulmonary hypertension. Thereafter, we linked his pulmonary hypertension with hemolytic anemia because his red blood cells appeared as leptocytes, acanthytes, and stomatocytes on scanning electron microscopy. It is important to confirm the diagnosis of hemolytic anemia, and splenectomy should be performed with due consideration of whether patients have hemolytic anemia.

Anemia, Hemolytic↗
PubMed2005

Importance of atopic cough, cough variant asthma and sinobronchial syndrome as causes of chronic cough in the Hokuriku area of Japan.

OBJECTIVE: A prospective multicentre study was conducted to elucidate the causes of chronic cough in Japan. METHODOLOGY: All consecutive and unselected patients complaining of cough lasting 8 weeks or more, who visited our clinics from 1 June to 31 December 2001, were registered. The causes of chronic cough were diagnosed based on the criteria for definite and probable causes of cough as recommended by the Japanese Cough Research Society. RESULTS: Of the 248 patients enrolled, 72 patients (29.0%) were unavailable for follow up before their diagnostic assessment had been finalized. Among the 176 patients who were adequately assessed, a diagnosis was made in 165 patients (93.7%) either as single cause or as one of two causes: atopic cough in 48 (29.1%) and 11 patients (6.7%); cough variant asthma in 46 (27.9%) and nine patients (5.5%); cough predominant asthma in 14 (8.5%) and three patients (1.8%); and sinobronchial syndrome (SBS) in 28 (17.7%) and 14 patients (8.5%), respectively. A diagnosis of gastro-oesophageal reflux-associated cough was made in a total of four patients (2.4%). CONCLUSION: Atopic cough, asthmatic cough consisting of cough variant asthma and cough predominant asthma, and SBS are major causes of chronic cough in Japan.

Adolescent↗
PubMed2005

Late recurrence of invasive cervical cancer: twenty years' experience in a single cancer institute.

AIM: To estimate the characteristics of, and prognosis for, late recurrence of cervical cancer. METHOD: Between 1977 and 1996, of 1721 patients with invasive cervical cancer, 1157 survived more than 5 years. Twenty-eight patients whose cancer recurred after a disease-free interval of 5 years were retrospectively investigated. For 22 patients the cancer recurred after less than 10 years, for five patients it recurred between 10 and 20 years after the original occurrence, and in one patient the cancer recurred after more than 20 years. RESULTS: The histologic subtypes included 20 squamous cell carcinomas and eight adenocarcinomas. The initial therapies were surgery alone (on one patient), surgery and adjuvant radiotherapy (on 20 of the patients) and radiotherapy alone (on seven of the patients). Recurrence was initially diagnosed by internal or external examination (11 patients), chest X-ray (six patients) and computed tomography (11 patients). Rates of lymphogenous metastases were 19% of patients with primary surgery and 57% of patients without primary surgery, while those of hematogenous metastases were 48% of patients with primary surgery and none of patients without primary surgery (P = 0.023). The overall survival rate after recurrence was 50.5% after 2 years and 22.3% after 5 years, respectively. Four of the patients survived for more than 3 years without evidence of disease; these patients all had recurrence outside the irradiated field and achieved complete remission with radiotherapy. CONCLUSIONS: Late recurrence of cervical cancer was frequently observed in patients with initial treatment, including radiotherapy. Some had very long disease-free intervals, but many were diagnosed by ordinary internal or external examination or chest X-ray. Patients with primary surgery experienced recurrence less frequently in the case of lymph node metastasis than was the case for hematogenous metastasis. Radiotherapy was effective and improved prognosis, especially for recurrence of cancer outside the irradiated field.

Adenocarcinoma↗
PubMed2005

Severe community-acquired pneumonia in an intensive care unit: risk factors for mortality.

OBJECTIVE: To evaluate severe community-acquired pneumonia (SCAP) patients in an intensive care unit (ICU) with regard to risk factors for mortality and to compare ICU patients with matched non-ICU patients to evaluate whether our judgement for ICU admission was appropriate or not. MATERIALS AND METHODS: During a 7-year period, all patients with CAP who were admitted to the ICU were examined. They underwent clinical and radiographic evaluations, and two commonly used severity of illness scores were also calculated using the Simplified Acute Physiological Score (SAPS) and the Acute Physiology and Chronic Health Evaluation (APACHE) II methods. To detect risk factors for ICU admission using existing guidelines, each study patient was matched with two patients hospitalized in a general medical ward. RESULTS: Seventy-two patients were identified during the study period. Their mean age was 72.9 years, and 35 patients (48.6%) subsequently died. For the univariate analysis, there were significant differences with the pulse rate > or = 130/min, blood urea nitrogen > or = 30 mg/dl, multilobar shadow, SAPS > or = 13, APACHE II > or = 23, and the occurrence of septic shock between the survivors and those who died. For the multivariate analysis, septic shock (p = 0.0005, odds ratio of 26.6) and blood urea nitrogen > or = 30 mg/dl (p = 0.037, odds ratio of 5.38) were associated with mortality. Regarding the characteristics of different clinical predictions for ICU admission, the revised American Thoracic Society criteria might have been the most accurate. CONCLUSION: Septic shock was associated with high mortality, which is a more accurate and higher predictor of mortality than was physical examination, laboratory or radiographic findings.

Aged↗
PubMed2005

Primary alveolar hypoventilation syndrome complicated with antiphospholipid syndrome.

A 32-year-old woman was transported to our hospital by ambulance because of loss of consciousness and breathing induced by drug intoxication. After general status was recovered, her arterial blood gas analysis under breathing room air revealed hypercapnia and hypoxemia which were caused by hypoventilation. After exclusion of apparent pulmonary, neuromuscular and central nerve diseases, she was diagnosed with primary alveolar hypoventilation syndrome. She had the complication of antiphospholipid syndrome (APS), suggesting the possibility of small lesions of the brainstem due to APS, which were too small to be detected on CT or MRI; these small lesions could cause injuries to the respiratory center.

Adult↗
PubMed2005

Characterization of the prostaglandin biosynthetic pathway in non-small cell lung cancer: a comparison with small cell lung cancer and correlation with angiogenesis, angiogenic factors and metastases.

To investigate the components of the prostaglandin biosynthetic pathway, the characteristics of cyclooxygenase (COX)-1, COX-2, hematopoietic prostaglandin D synthase (hPGDS), microsomal prostaglandin E synthase (mPGES), and thromboxane synthase (TXS) were examined for autopsied cases with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Autopsied patients (n=120) with lung cancer were examined, of whom 25 had SCLC and 95 had NSCLC. Immunostaining was performed for COX-1, COX-2, hPGDS, mPGES, TXS, CD34, vascular endothelial growth factor (VEGF), and basic fibroblastic growth factor (bFGF). The immunostaining scores of the prostaglandin biosynthetic pathway markers were significantly higher for adenocarcinoma than for SCLC (p<0.0001). In addition, there were significant correlations between two markers of the prostaglandin biosynthetic pathway for cases with SCLC and NSCLC. For NSCLC, the mean immunostaining scores for the prostaglandin biosynthetic pathway markers were significantly higher for cases with high count groups than low count groups for MVD, VEGF and bFGF, except COX-2 and MVD, and COX-2 and bFGF. The mean immunostaining scores for COX-1, COX-2, mPGES, and TXS were significantly higher for cases with more metastatic organs who had NSCLC. Prostaglandin biosynthetic pathway markers may act synergistically and enhance tumor angiogenesis, the expression of angiogenic factors, and metastases in patients with NSCLC.

Adult↗
PubMed2005

Predictors for typical asthma onset from cough variant asthma.

Cough variant asthma is recognized to be a precursor of asthma or preasthmatic state because nearly 30% patients with cough variant asthma develop typical asthma within several years. However, predictors for risk of typical asthma onset from cough variant asthma are unknown. Forty-one patients with cough variant asthma (median age 50 years, 13 men and 28 women), who had undertaken spirometry, bronchial reversibility test, methacholine provocation test, measurements of peripheral blood eosinophil count, serum total IgE, and specific IgE to common allergens, and induced sputum eosinophil count at presentation, were followed up with special emphasis on typical asthma onset during 1 year or more (median 4 years, range 1-12.4). Long-term inhaled corticosteroids (ICS) were taken in 27 patients. Univariate and multivariate logistic analyses were performed to determine the predictors for typical asthma onset. Asthma onset was recognized in 7 patients. Bronchial hyperresponsiveness, peripheral blood eosinophil count, and no use of ICS were significant predictors for the typical asthma onset by univariate analysis. However, only bronchial hyperresponsiveness was the significant predictor when multivariate analysis was used (adjusted OR 0.028, 95% CI 0.001-0.783, p = 0.0355). Bronchial hyperresponsiveness may be the most important predictor for risk of typical asthma onset from cough variant asthma.

Asthma↗
PubMed2005

[Two cases of pulmonary infection by Mycobacterium abscessus in which drug susceptibility testing results conflicted with clinical courses].

We encountered two cases of pulmonary infection by Mycobacterium abscessus (M. abscessus). [Case 1] A 66-year-old man who had been treated for non-tuberculous mycobacterium in the past was admitted because of productive cough. His chest X-ray film showed cavitation and direct microscopy of sputum revealed positive acid-fast bacilli (AFB). He was given rifampicin (RFP), ethambutol (EB), and clarythromycin (CAM), and then his symptoms and radiographic findings improved. [Case 2] A 74-year-old man with multiple myeloma as an underlying disease was admitted because of a cavitation found on chest radiography and a positive result for AFB in his sputum. Standard antituberculous drug therapy with isoniazid (INH), RFP, EB, and pyradinamide (PZA) was initiated and then the chest radiographic findings improved. As M. abscessus was isolated two weeks after the induction of therapy, the therapeutic regimen was changed to another combination therapy consisting of EB, clarithromycin (CAM) and ciprofloxacin (CPFX), and then his symptoms and radiographic findings were further improved. In both cases, the bacilli found in their sputum were identified as M. abscessus by DNA hybridization. They were completely resistant to all anti-tuberculosis agents and many antibiotics with a high value of MIC. However, their symptoms, radiographic abnormalities and the results of sputum examination improved following chemotherapy. The results obtained by MIC measurement were inconsistent with the clinical outcomes. The measurement of the MIC value of antibiotics do not necessarily predict its therapeutic effect.

Aged↗