Biomedical subjects

Masaki Fujimura

Publications and source records attributed to Masaki Fujimura.

At least 55 records · Page 3Linked to original sources

PubMed2004

Treatment of atopic cough caused by Basidiomycetes antigen with low-dose itraconazol.

We report two patients with atopic cough due to Basidiomycetes antigen. One patient was a 27 year-old woman and the other was a 17 year-old boy. Both patients visited our hospital because of severe nonproductive cough. They did not have bronchial hyperresponsiveness to methacholine or heightened bronchomotor tone. Bronchodilator therapy was not effective for their cough. Her symptoms worsened in her office and his in his house, suggesting existence of etiologic agent(s) in their environments. Basidiomycetes was isolated from the woman's office and from the boy's house, and the bronchoprovocation test with Basidiomycetes antigen was positive. Low dose itraconazol (50 or 100 mg/day) given for two weeks eliminated cough in both patients. This is the first report describing the effectiveness of low dose antifungal therapy for atopic cough caused by Basidiomycetes antigen.

Adolescent↗

PubMed2004

A guinea pig model for cough variant asthma and role of tachykinins.

Cough variant asthma is known as a major cause of chronic cough. Fundamental features of cough variant asthma are prolonged nonproductive cough responding to bronchodilator therapy, no history of wheezing or dyspnea attack, normal cough sensitivity, and slightly increased bronchial responsiveness. Animal model of cough variant asthma has not been reported. The aim of this study was to establish an animal model for studying detailed pathophysiology of cough variant asthma. Bronchial responsiveness to methacholine and cough reflex sensitivity to capsaicin were measured 72 hours after antigen (ovalbumin, OA) inhalation in actively sensitized guinea pigs. Next, cough number and specific airway resistance (sRaw) were measured during 20 minutes following reinhalation of OA solution, which was carried out 72 hours after the first OA inhalation, and then total cell number and cell differentials in bronchoalveolar lavage fluid (BALE) were measured. Bronchial responsiveness to methacholine, but not cough reflex sensitivity to capsaicin, was significantly increased 72 hours after the first inhalation of OA solution. Number of coughs, sRaw and total cell number in BALF increased significantly by the OA reinhalation, and the cough number and the increase in sRaw were significantly suppressed by beta2 agonist, procaterol. FK224, a specific neurokinin (NK) receptor antagonist, did not significantly influence the OA reinhalation-induced cough and increase in sRaw and total cell number in BALF in this model In conclusion, pathophysiologic feature of this animal model is similar to that of clinical cough variant asthma. Tachykinins may not play an important part in antigen-induced cough associated with bronchoconstriction and airway inflammation in cough variant asthma.

Airway Resistance↗

PubMed2004

Th2 cytokine inhibition and cough in asthmatic and bronchitic patients.

BACKGROUND: Activated T helper lymphocytes are present in the airway and their production of cytokines is important in the pathogenesis of asthma, however, the relationship between T helper lymphocyte-derived cytokines and airway cough reflex sensitivity remains unknown. METHODS: The effect of the orally active Th2 cytokine inhibitor suplatast tosilate on cough response to inhaled capsaicin was examined in eleven patients with stable atopic asthma and compared with patients having non-atopic asthma and chronic bronchitis (the latter of which is not related to Th2 cytokines). Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough reflex sensitivity. Concentration of serum total IgE level was also measured after treatment with suplatast tosilate. RESULTS: The cough threshold after two weeks treatment with suplatast tosilate was significantly greater than the value with placebo accompanied by decrease of serum IgE level in atopic asthmatics. This significance was not observed in patients with non-atopic asthma or chronic bronchitis. CONCLUSIONS: Th2 cytokines may be possible modulators augmenting airway cough reflex sensitivity in atopic asthmatic airways but not in non-atopic asthmatic or bronchitic airways.

Adult↗

PubMed2004

Allergic bronchopulmonary fungal disease caused by Saccharomyces cerevisiae.

We describe a patient who presented with dry cough, low-grade fever, and focal patchy shadow of pulmonary infiltrates. Remarkably, the prospective etiological agent, Saccharomyces cerevisiae was purely and repeatedly cultured from her sputum. Allergic bronchopulmonary mycosis (ABPM) was diagnosed based on clinical, serological, and pathological criteria. Although the patient described here satisfied only three of the criteria, the conclusion that the allergic bronchopulmonary disease in our case was induced by S. cerevisiae was made based on the following evidence: 1) S. cerevisiae was repeatedly isolated from the patient's sputum, 2) anti-S. cerevisiae antibody was detected in her serum, and 3) bronchoprovocation test to S. cerevisiae antigen was positive. We present here a case of allergic bronchopulmonary fungal disease caused by S. cerevisiae antigen.

Adult↗

PubMed2004

Chronic hypersensitivity pneumonitis caused by Aspergillus complicated with pulmonary aspergilloma.

A 57-year-old man consulted our hospital with a history of the gradual onset of dyspnea and a productive cough. Chest computed tomographic (CT) scans showed a nodular shadow in a cavity lesion, and reticulonodular, cystic, and ground-grass opacities in the bilateral lung fields with honeycombing. He was diagnosed as having pulmonary aspergilloma and idiopathic pulmonary fibrosis (IPF). As an outpatient, he suffered from dyspnea upon physical exertion with exacerbation of the high-resolution CT (HRCT) opacities. An inhalation provocation test for Aspergillosis fumigatus was positive and chronic hypersensitivity pneumonitis (CHP) caused by Aspergillus was finally diagnosed. Insidious CHP is sometimes misdiagnosed as IPF. The diagnosis of insidious CHP should be made on the basis of a detailed history, specific HRCT findings, and lymphocyte-dominant bronchoalveolar lavage fluid cell findings.

Alveolitis, Extrinsic Allergic↗

PubMed2004

[Transient liver injury caused by gefitinib].

Gefitinib blocks epidermal growth factor receptor autophosphorylation and subsequently the signal transduction pathways implicated in proliferation, metastasis, invasion, and angiogenesis. Reported adverse reactions to gefitinib include liver injury that is not fully understood. Liver injury was observed in 5 (12.2%) of 41 patients with non-small cell lung cancer who received gefinitib monotherapy. Onset of liver injury was seen between 28 and 56 days after initiation of administration. Two patients had Grade 2 liver injury and 3 patients, Grade 3. In 4 patients, liver injury was temporary, lasting during a period of continuous gefitinib administration. In another patient, gefitinib was discontinued because of the onset of liver injury, which improved when gefitinib administration was restarted. Gefitinib is necessary in most patients whose lung cancer is refractory to cytotoxic chemotherapy, because no other treatment regimens are available at present. The rate of liver injury in cases treated with gefitinib is high, and so it is necessary to observe liver function carefully, but the liver injury due to this drug is often transient. However, the use of gefitinib in many cases appears to be a necessity.

Adult↗

PubMed2004

[Atopic cough caused by basidiomycetes antigen; the importance as a fungal aeroallergen in occupational environment].

We report here a 28-year-old woman with severe atopic cough in which Basidiomycetes antigen was an etiologic agent. She did not have bronchial hyperresponsiveness to methacholine or heightened bronchomotor tone. Bronchodilator therapy was not effective against her coughing. Her cough worsened in her office, suggesting the existence of some etiologic agents. Basidiomycetes was isolated from her office, and bronchoprovocation test with Basidiomycetes antigen was positive. 19 coworkers and 29 control subjects underwent skin test with Basidiomycetes extract. The rate of positive skin test to Basidiomycetes was significantly greater in coworkers than in control subjects (P=0.0069). These results indicate that a significant number of coworkers are sensitized to Basidiomycetes antigen and suggest that the Basidiomycetes may be an important fungal aeroallergen in occupational environment.

Adult↗

PubMed2004

[A case of pulmonary sarcoidosis with usual interstitial pneumonia-like lesions distributed predominantly in the lower lung fields].

In 2000, in a 75-year-old man, nodular and reticular opacities were detected in both lower lung fields. He was admitted to our hospital for further examination of these abnormal shadows. Bronchoscopic examination revealed pulmonary sarcoidosis. Prednisolone was prescribed because cardiac sarcoidosis was diagnosed as a clinical complication. In April 2002, the patient visited our hospital for dyspnea on effort. Chest radiography and computed tomography showed nodular and reticular opacities in the right upper lobe, and video-assisted thoracoscopic surgery was performed on the basis of a histological diagnosis. The histological findings of the biopsied specimens revealed a lesion of the type seen in usual interstitial pneumonia, whereas non-caseous granulomas were not detected. His symptoms and chest radiographic findings improved and stabilized with prednisolone and azathioprine. In the present case of pulmonary sarcoidosis, the reticular and nodular opacities predominantly distributed in both lower lung fields, and the histological findings obtained by video-assisted thoracoscopic surgery showed a usual interstitial pneumonia-like lesion. These findings may assist in the understanding of the process of development of pulmonary sarcoidosis.

Aged↗

PubMed2004

[Comparison of the bronchodilator effect of salbutamol between pressure metered dosed inhaler and dry powder inhaler in patients with stable bronchial asthma].

Recently, dry powder inhaler (DPI) was more available than pressure metered dosed inhaler (pMDI) for the inhalation therapy of the respiratory disease. But there are differences in the lung deposition of the drug in these devices. We investigated the bronchodilator effect of salbutamol inhalation with two device, pMDI and Tubuhaler on the stable 8 asthmatic patients. The time course of FEV1 had a no significant difference between two devices. DeltaAUC (=difference between area under the curve for time course of increase in FEV1 via pMDI and via DPI) and Deltamax FEV1 (=difference between maximum increases in FEV1 following inhalation of salbutamol via pMDI and DPI) were defined as the index of difference of bronchodilator effect between the two devices. PMDI was more effective on improving the pulmonary function in subjects with severely decreased FEV1 and FEV1% than DPI. These results may reflect the correlation of inspiratory flow rate and drug deposition. PMDI is still useful on the part of asthmatic patients with decreased pulmonary function.

Adult↗

PubMed2004

[A case of successful desensitization therapy for isoniazid-induced pneumonitis].

A 65-year-old man was admitted to hospital for treatment of pulmonary tuberculosis. He was treated with isoniazid (INH), rifampicin (RFP), ethambutol (EB), and pyrazinamide (PZA). On the 14th day, he developed a fever and interstitial pneumonia, which improved promptly after discontinuation of the antituberculous drugs. Drug lymphocyte stimulation tests against INH, RFP and PZA were negative. However, the provocation test on INH (only) was positive, leading to a diagnosis of pneumonitis caused by INH. We then tried desensitization of INH over a period of two weeks, which was successful and occurred without any clinical event. In the past, five cases of INH-induced pneumonitis were reported, but desensitization of INH did not occur in any. We conclude that physicians should be aware not only of paradoxical reactions but also of drug-induced pneumonitis when a new pulmonary infiltrate develops in the course of tuberculosis treatment. Furthermore, drug desensitization may be possible in some cases of drug-induced pneumonitis.

Aged↗

PubMed2004

[A case of anhidrotic ectodermal dysplasia diagnosed during investigation of asthmatic attack].

A 24-year old man was hospitalized because of a severe asthmatic attack in August 2003. The asthma attack was well controlled by mechanical ventilation, intravenous hydrocortisone and inhaled beta2-agonist. Physical examination revealed sparse hair, reduced sweating and hypodontia. We also confirmed the absence of sweat glands in a biopsied skin specimen. The diagnosis based on these findings was anhidrotic ectodermal dysplasia A mutation in the EDA (ectodysplasin-A) gene which led to an X-linked anhidrotic ectodermal dysplasia was found, and the same genetic mutation was detected in the patient's mother.

Adult↗

PubMed2003

Gastric distension-induced release of 5-HT stimulates c-fos expression in specific brain nuclei via 5-HT3 receptors in conscious rats.

We examined c-fos expression in specific brain nuclei in response to gastric distension and investigated whether 5-HT released from enterochromaffin (EC) cells was involved in this response. The role of 5-HT3 receptors in this mechanism was also addressed. Release of 5-HT was examined in an ex vivo-perfused stomach model, whereas c-fos expression in brain nuclei induced by gastric distension was examined in a freely moving conscious rat model. Physiological levels of gastric distension stimulated the vascular release of 5-HT more than luminal release of 5-HT, and induced c-fos expression in the nucleus of the solitary tract (NTS), area postrema (AP), paraventricular nucleus (PVN), and supraoptic nucleus (SON). The c-fos expression in all these brain nuclei was blocked by truncal vagotomy as well as by perivagal capsaicin treatment, suggesting that vagal afferent pathways may mediate this response. Intravenous injection of 5-HT3 receptor antagonist granisetron blocked c-fos expression in all brain nuclei examined, although intracerebroventricular injection of granisetron had no effect, suggesting that 5-HT released from the stomach may activate 5-HT3 receptors located in the peripheral vagal afferent nerve terminals and then induce brain c-fos expression. c-fos Positive cells in the NTS were labeled with retrograde tracer fluorogold injected in the PVN, suggesting that neurons in the NTS activated by gastric distension project axons to the PVN. The present results suggest that gastric distension stimulates 5-HT release from the EC cells and the released 5-HT may activate 5-HT3 receptors located on the vagal afferent nerve terminals in the gastric wall leading to neuron activation in the NTS and AP and subsequent activation of neurons in the PVN and SON.

Animals↗

PubMed2003

Ghrelin induces fasted motor activity of the gastrointestinal tract in conscious fed rats.

Ghrelin is a newly discovered orexigenic peptide originating from the stomach. However, its action in regulating the fed and fasted motor activity of the digestive tract is not fully understood. In the present study, we examined the effects of intracerebroventricular (I.C.V.) and intravenous (I.V.) injection of ghrelin on the physiological fed and fasted motor activities in the stomach and duodenum of freely moving conscious rats. I.C.V. and I.V. injection of ghrelin induced fasted motor activity in the duodenum in normal fed rats, while I.V. injection of ghrelin induced fasted motor activity in both the stomach and duodenum in vagotomized rats. The effects of I.C.V. and I.V. injected ghrelin were blocked by growth hormone secretagogue receptor (GHS-R) antagonist given by the same route and also blocked by immunoneutralization of neuropeptide Y (NPY) in the brain. The effects of I.V. injected ghrelin were not altered by I.C.V. injection of GHS-R antagonist in vagotomized rats. Injection of GHS-R antagonist blocked the fasted motor activity in both the stomach and duodenum in vagotomized rats but did not affect the fasted motor activity in normal rats. Low intragastric pH inhibited the effect of ghrelin. The present results indicate that ghrelin is involved in regulation of fasted motor activity in the stomach and duodenum. Peripheral ghrelin may induce the fasted motor activity by activating the NPY neurons in the brain, probably through ghrelin receptors on vagal afferent neurons. Once the brain mechanism is eliminated by truncal vagotomy, ghrelin might be primarily involved in the regulation of fasted motor activity through ghrelin receptors on the stomach and duodenum. The action of ghrelin to induce fasted motor activity is strongly affected by intragastric pH; low pH inhibits the action.

Animals↗

PubMed2003

Lack of adrenomedullin on antigen-induced bronchoconstriction in guinea pigs in vivo.

Antigen challenge can provoke acute bronchoconstriction, recognized as immediate asthmatic response (IAR), but the evolving events in this reaction are not well defined. Recently, a novel peptide, designated adrenomedullin, was isolated from human pheochromocytoma, and has been shown to have potent systemic and pulmonary vasodilator activity.The purpose of this study was to elucidate the influence of adrenomedullin in the development of IAR. Passively sensitized guinea pigs were anesthetized and treated with diphenhydramine hydrochloride, and then artificially ventilated. Ovalbumin was inhaled after an intravenous administration of adrenomedullin. Other studies were performed in naive guinea pigs to investigate the airway responses to inhaled methacholine or histamine after an intravenous administration of adrenomedullin. Antigen challenge caused bronchoconstriction in sensitized guinea pigs. Adrenomedullin did not inhibit the antigen-induced bronchoconstriction in sensitized guinea pigs or the dose-dependent responses to inhaled methacholine or histamine in naive animals in spite of its vasodilating effect. We conclude that an intravenous administration of adrenomedullin does not influence antigen-induced bronchoconstriction or bronchial responsiveness to inhaled methacholine or histamine in vivo.

Adrenomedullin↗

PubMed2003

Bronchodilator effects of intravenous olprinone, a phosphodiesterase 3 inhibitor, with and without aminophylline in asthmatic patients.

AIMS: There is no evidence demonstrating the clinical usefulness of phosphodiesterase (PDE) inhibitors in the treatment of asthma, although PDE3 and 4 inhibitors have received much attention for the treatment of bronchial asthma. We compared the bronchodilator effects of intravenously administered olprinone, a selective PDE3 inhibitor, and aminophylline, a nonselective PDE inhibitor, both alone and concomitantly. METHODS: In 12 patients with mild stable asthma, we compared the acute bronchodilator effects of the following two drugs, alone and together using a double-blind crossover design: intravenous administration of olprinone, 30 micro g min-1; aminophylline, 2.25 mg min-1; and olprinone plus aminophylline over a total period of 150 min. RESULTS: Mean maximal increase (95% confidence interval) in the FEV1 was 7.8% (2.4, 13.2), 17.1% (10.0, 24.2), 16.6% (11.2, 22.0), and 1.0% (-1.1, 3.1) during infusion of aminophylline, olprinone, aminophylline and olprinone, and saline, respectively. The magnitude of bronchodilatation produced by olprinone was greater than that by aminophylline. The combination of aminophylline and olprinone did not produce any greater bronchodilatation than olprinone alone. Olprinone alone or in combination with aminophylline lowered diastolic blood pressure, and increased heart rate. CONCLUSIONS: These results suggest that the intravenous administration of PDE3 inhibitors exhibits a bronchodilatory effect. There are no additive or synergistic effects of administration of olprinone and aminophylline at the same time.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2003

Effect of carbocysteine on cough reflex to capsaicin in asthmatic patients.

AIMS: Cough, one of the main symptoms of bronchial asthma, is a chronic airway inflammatory disease with functionally damaged bronchial epithelium. Recently, we established an animal model with cough hypersensitivity after antigen challenge and clearly showed the protective effect of carbocysteine in this model. This study was designed to investigate the clinical effect of carbocysteine for cough sensitivity in patients with bronchial asthma. METHODS: The effects of the two orally active mucoregulatory drugs, carbocysteine and ambroxol hydrochloride, on cough response to inhaled capsaicin were examined in 14 patients with stable asthma. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough sensitivity. RESULTS: Geometric mean values of the cough threshold at run-in (baseline) and after 4 weeks' treatment of placebo, 1500 mg day-1 of carbocysteine and 45 mg day-1 of ambroxol hydrochloride were 12.8 micro M (95% confidence interval [CI] 5.5, 29.6), 11.0 micro M (95% CI 4.4, 27.5), 21.0 micro M (95% CI 8.8, 50.2) and 11.6 micro M (95% CI 5.8, 23.3), respectively. The cough threshold for carbocysteine was significantly greater than those of ambroxol hydrochloride (P = 0.047) and placebo (P = 0.047), respectively. CONCLUSIONS: These findings indicate that carbocysteine administration may be a novel therapeutic option for asthmatic patients, especially with cough variant asthma.

Adult↗

PubMed2003

A case of hypersensitivity pneumonitis caused by Humicola fuscoatra.

A 51-year-old housewife with hypersensitivity pneumonitis caused by Humicola fuscoatra is reported. The diagnosis was made by an inhalation challenge with H. fuscoatra antigen. She was admitted for diagnosis and treatment of a fever and productive cough. Auscultation of her lungs revealed inspiratory fine crackles. Her chest CT showed diffuse miliary nodules in a centri-lobular distribution with patchy ground glass opacities. Findings of transbronchial lung biopsy and BAL fluid were compatible with a hypersensitivity pneumonitis. Her symptoms worsened on returning home, which suggested the existence of some aetiological agent in the subject's house. H. fuscoatra, Penicillium decumbens and Aspergillus versicolor were isolated from a number of rooms. High titres of serum anti H. fuscoatra, P. decumbens and A. versicolor were detected. Inhalation challenge tests with both P. decumbens and A. versicolor antigen were negative, in contrast to that with H. fuscoatra which was positive. Based on these results, we advised the patient to cleanse her entire house. Since cleaning, her symptoms have not worsened upon returning home. This is the first report of hypersensitivity pneumonitis caused by H. fuscoatra antigen.

Alveolitis, Extrinsic Allergic↗

PubMed2003

Thromboxane antagonism and cough in chronic bronchitis.

BACKGROUND: The increased eicosanoid synthesis has been suggested as the underlying mechanism of chronic productive cough in patients with chronic bronchitis. METHOD: The effects of the orally active thromboxane A2 (TxA2) receptor antagonist seratrodast and the cysteinyl leukotrienes (cLTs) receptor antagonist pranlukast on cough response to inhaled capsaicin were examined in sixteen patients with stable chronic bronchitis. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough sensitivity. RESULTS: The cough threshold was significantly increased compared with placebo after four-week treatment with seratrodast, but not after treatment with pranlukast. CONCLUSIONS: TxA2, but not cLTs, may be a possible modulator augmenting airway cough sensitivity in chronic bronchitis. Thromboxane antagonism may be considered to be one of the therapeutic options for the treatment of chronic productive cough.

Adult↗