Biomedical subjects
Publications and source records attributed to T Ohka.
A 49-year-old female presented with a 1-month history of cough and low-grade fever. Echocardiography showed a large mass in the right ventricle and percutaneous right ventricular endomyocardial biopsy provided the histologic diagnosis. Despite radiotherapy and chemotherapy, the patient died. At autopsy, the metastatic deposit in the heart was larger than the primary cervical carcinoma.
A 70-year-old man was admitted to the hospital because of mild dyspnea, a cough, and hemoptysis. A chest X-ray film and a computed tomographic scan showed a mass in the S1.2 region of the left lung, and swollen mediastinal lymph noes. Cytologic examination of sputum sample resulted in the diagnosis of lung cancer. The tumor did not respond to chemotherapy, and the patient died after seven months. Autopsy disclosed a solid tumor of left lung and many cystic lesions in the liver. Histological examination of the lung lesion revealed adenosquamous cell carcinoma. Metastatic lesions in the liver consisted of adenosquamous cell carcinoma, with predominantly squamous cell carcinoma. Cases of lung cancer in which hepatic metastases have many cystic cavities are rare.
A 53-year-old man was admitted to the hospital because of productive coughing general malaise, and right-sided chest pain. At 41 years of age he was given a diagnosis of gastric cancer, underwent a and gastrectomy, was treated with anti-cancer drugs. At 49 years of age he suffered from atypical mycobacteriosis and received anti-tuberculosis drugs for 1 year. A chest X-ray film showed infiltrative shadows with a cavity in the right upper lung field. Semi-invasive aspergillosis was diagnosed on the basis of the clinical and radiographic findings, positive sputum cultures, and positive serologic tests. After 8 months of therapy with intravenous and oral fluconazole, no pulmonary aspergillosis was evident. Treatment with fluconazole was effective in this case of semi-invasive aspergillosis.
No study has investigated the effects of ethanol on bronchial responsiveness in patients with alcohol-induced asthma, although acetaldehyde, which is a metabolite of ethanol and is thought to be a main factor in alcohol-induced asthma, causes both bronchoconstriction and bronchial hyperresponsiveness. The purpose of this study was to investigate the direct action of ethanol on the airway in patients with alcohol-induced asthma. First, we investigated the bronchial response to inhalation of ascending doses (5, 10, and 20%) of ethanol in nine patients with alcohol-induced asthma. Then, the bronchial responsiveness to methacholine was measured in 14 patients who were pretreated with saline or 20% ethanol in a double-blind, randomized, placebo-controlled, crossover fashion. Ascending doses of inhaled ethanol caused no significant changes in FEV1. The methacholine concentrations producing a 20% fall in FEV1 (PC20-MCh) after 20% ethanol (0.769 mg/ml, GSEM 1.514) were significantly (P = 0.0357) higher than those after saline (0.493 mg/ml, GSEM 1.368). This indicates that ethanol has a reducing effect on nonspecific bronchial responsiveness in patients with alcohol-induced asthma; this paper is the first report on the effects of ethanol on bronchial responsiveness.
1. In this study, the role of neuropeptides in antigen-induced bronchoconstriction and bronchial responsiveness in guinea-pigs was evaluated by use of phosphoramidon, the inhibitor of neutral endopeptidases (NEP), the NK1 receptor antagonist, FK888, and the dual NK1/NK2 receptor antagonist, FK224. The role of endogenous tachykinins in bronchial hyperresponsiveness induced by inhaled capsaicin was also observed with FK888 and FK224. 2. Allergic bronchoconstriction and bronchial responsiveness was evoked by inhalation of ovalbumin (OA), and increasing doses of methacholine were inhaled at 5-min intervals for 30 min after OA challenge in passively sensitized and artificially ventilated guinea-pigs. Animals were treated with a 30 s inhalation of phosphoramidon (10(-3)M) or saline 10 min before the OA challenge. FK888 (1.0 or 10 mg kg-1) or FK224 (1.0 or 10 mg kg-1) was administered intravenously 5 min before the OA challenge. 3. Treatment with phosphoramidon did not alter the increase in the lateral pressure at the tracheal tube (Pao) caused by OA inhalation or the increase in bronchial response to methacholine following the allergic reaction. Pretreatment with FK224 did not inhibit the increase in Pao after antigen provocation but did significantly inhibit antigen-induced bronchial hyperresponsiveness in a dose-dependent manner, while FK888 did not affect either allergic bronchoconstriction or post-allergic bronchial hyperresponsiveness. 4. Histamine, 25, 50, 100 or 200 micrograms ml-1 was inhaled for 20 s at 5-min intervals in non-sensitized guinea-pigs which were pretreated with inhalation of subthreshold dose of capsaicin (10(-7) M). FK888 or FK224, each at a dose of 0.1 or 1.0 mg kg-1, or vehicle was given to guinea-pigs intravenously 3 min before inhalation of capsaicin. The capsaicin inhalation significantly potentiated bronchial responsiveness to histamine, compared with control. The capsaicin-induced bronchial hyperresponsiveness was completely blocked by FK224 in a dose-dependent manner but not by FK888. 5. These results suggest that NK2 receptors rather than NK1 receptors may play an important role in bronchial hyperresponsiveness induced by antigen challenge as well as capsaicin while tachykinins do not play a primary role in the acute bronchospasm elicited by antigen challenge in passively sensitized guinea-pigs.
A 50-year-old woman was transported to a hospital complaining of marked general malaise and epigastralgia with diarrhea and vomiting. Her electrocardiogram showed sinus arrest with a duration of nearly 8 sec. Atrial pacing with an external pacemaker improved her symptoms promptly. Following transfer to our hospital 3 days later, bradyarrhythmia was not detected despite the removal of the external pacemaker. Transient atrial fibrillation was found in our hospital, and she was diagnosed as hyperthyroidism based on findings of finger tremor, exophthalmos, diffuse goiter and an abnormally high level of thyroid hormone. On cardiac catheterization, left ventriculography showed anterior wall hypokinesis and mild mitral regurgitation. Coronary arteriography showed the absence of organic stenosis. Right ventricular endomyocardial biopsy showed myocardial hypertrophy and partial disarray, but no findings of myocarditis. Electrophysiological study showed the normal upper range of AH-time (120 msec) and HV-time (50 msec), and prolongation of corrected sinus recovery time (CSRT, 955 msec). After a euthyroid state was successively induced for about 10 days by methylmercaptoimidazole therapy, AH-time, HV-time and CSRT were shortened to 85, 35 and 290 msec respectively. Her complaints and sick sinus syndrome disappeared after the treatment of hyperthyroidism without a pacemaker.
We wanted to evaluate the effect of terfenadine, a selective H1-receptor antagonist, on alcoholic beverage-induced bronchoconstriction. Eight patients with alcohol-induced asthma received terfenadine (60 mg, twice on the test day) or placebo, with the last dosing 2 h before the test in a double-blind, randomized, cross-over manner. On two separate study days, each subject drank the same brand and volume of alcoholic beverage (beer or Japanese saké), and bronchoconstriction was assessed as change in peak expiratory flow (PEF) over 120 min postchallenge. Inhalation challenges were performed with the same alcoholic beverage with which they had been orally challenged. The mean (SEM) percentage fall in PEF 15, 30, 45, 60, 90 and 120 min after the oral alcohol challenge was significantly reduced from 12.0 (3.1), 17.0 (1.7), 15.8 (2.3), 15.2 (3.4), 16.6 (4.8) and 14.7 (5.2)%, to 2.6 (1.8), 2.1 (1.6), 3.9 (1.2), 5.7 (2.2), 6.5 (2.6), 5.1 (1.6)%, respectively, by terfenadine. No significant bronchoconstriction was observed after the inhalation challenge. We conclude that the release of histamine makes a major contribution to alcoholic beverage-induced bronchoconstriction in Japanese asthmatic patients, and that histamine H1 antagonists may be effective in preventing alcoholic beverage-induced bronchoconstriction.
BACKGROUND: It has recently been reported that acetaldehyde induces bronchoconstriction indirectly via histamine release. However, no study has been performed to assess whether acetaldehyde worsens bronchial responsiveness in asthmatic subjects so this hypothesis was tested. METHODS: Methacholine provocation was performed on three occasions: (1) after pretreatment with oral placebo and inhaled saline (P-S day), (2) after placebo and inhaled acetaldehyde (P-A day), and (3) after a potent histamine H1 receptor antagonist terfenadine and acetaldehyde (T-A day) in a double blind, randomised, crossover fashion. Nine asthmatic subjects inhaled 0.8 mg/ml acetaldehyde or saline for four minutes. After each inhalation a methacholine provocation test was performed. RESULTS: Methacholine concentrations producing a 20% fall in FEV1 (PC20-MCh) on the P-A day (0.48 mg/ml, 95% CI 0.21 to 1.08) and T-A day (0.41 mg/ml, 95% CI 0.22 to 0.77) were lower than those on the P-S day (0.85 mg/ml, 95% CI 0.47 to 1.54). There was no change in the PC20-MCh between the P-A and T-A days. A correlation was observed between the logarithmic values of PC20-MCh (log PC20-MCh) on the P-S day and the potentiating effect of acetaldehyde on the methacholine responsiveness [(log PC20-MCh on P-A day)-(log PC20-MCh on P-S day)] (rho = 0.82). CONCLUSIONS: Acetaldehyde induces bronchial hyperresponsiveness in patients with asthma by mechanisms other than histamine release.
We recently reported that inhaled acetaldehyde causes bronchoconstriction indirectly via histamine release in patients with asthma. The purpose of this study was to investigate a role of thromboxane A2 in acetaldehyde-induced bronchoconstriction in asthmatic airways. We investigated the bronchial response to inhalation of ascending doses (5, 10, 20, and 40 mg/ml) of acetaldehyde in nine asthmatic subjects who were treated with placebo or OKY-046, a selective thromboxane A2 synthetase inhibitor, of 200 mg twice a day for 3 days, and 200 mg on the fourth day (test day) in a double-blind, randomized, placebo-controlled, crossover fashion. Percentage decreases in FEV1 caused by 20 and 40 mg/ml of acetaldehyde inhalation were significantly (p < 0.05 and p < 0.01, respectively) prevented by the pretreatment with OKY-046. Geometric mean value (geometric standard error of the mean) of acetaldehyde concentration producing a 20 percent fall in FEV1 (PC20-Ac-CHO) was significantly (p < 0.01) greater with the OKY-046 pretreatment (72.2 [1.1] mg/ml) than with the placebo pretreatment (19.8 [1.2] mg/ml). We conclude that thromboxane A2 is one of contributors to acetaldehyde-induced bronchoconstriction in asthmatic subjects. It suggests that thromboxane A2 may play an important role in endogenous histamine-induced bronchoconstriction caused by acetaldehyde in asthmatic airways. We believe that this is a first report on the interaction between endogenous histamine and thromboxane A2 in asthmatic subjects.
A 31-year-old woman presented with hypertrophy of the left upper extremity and thrombocytopenia. Physical examination revealed splenomegaly, and laboratory investigation revealed thrombocytopenia, elevation of cross-linked fibrin degradation products (XDP), and thrombin-antithrombin III complex (TAT). A diagnosis of Klippel-Trenaunay-Weber (K-T-W) syndrome was established by the dermatologic findings and angiography of the extremities. A splenic cavernous lymphangioma was diagnosed by ultrasonography and angiography, and was confirmed by pathology following splenectomy. Post-operatively, the platelet count increased, and hemostatic parameters normalized. Cavernous lymphangioma is a rare complication of Klippel-Trenaunay-Weber syndrome. Splenectomy proved to be an effective therapy for both cavernous lymphangioma and consumptive coagulopathy in Klippel-Trenaunay-Weber syndrome.
A 80-year-old man was admitted to our hospital complaining of appetite loss, dry cough, and dyspnea on exertion. Chest X-ray film showed massive right pleural effusion. On physical examination, the right thorax was dull to percussion, and breath sounds of the right lung field were diminished. Examination of the cardiovascular system was unremarkable. Hepatosplenomegaly and ascites were not evident. The character of the pleural fluid was transudative. Cytological findings were negative and culture of the pleural fluid was normal. First, the pleural fluid was diminished by thoracic drainage. But, after the cessation of drainage, the pleural fluid soon reaccumulated. Abdominal ultrasonography showed typical liver cirrhosis pattern without ascites. An intraperitoneal injection of 99mTc-sulfur colloid was followed by positive uptake of radioactivity in the right pleural cavity from 1 hour after the injection, demonstrating the existence of a direct perito-pleural communication. Thus, the diagnosis of liver cirrhosis presenting with right pleural fluid, without ascites was made. This case indicates that the absence of ascites cannot exclude cirrhosis as the etiologic cause of pleural effusion.
It has been reported that acetaldehyde may be a main factor of alcohol-induced bronchoconstriction in Japanese patients with asthma. The purpose of this study was to investigate the direct action of acetaldehyde on the airway in asthmatic and healthy nonasthmatic subjects. We investigated the bronchial response to inhalation of ascending doses (5, 10, 20, and 40 mg/ml) of acetaldehyde in nine asthmatic subjects, who were treated with placebo or terfenadine for 4 days in a double-blind, randomized, placebo-controlled, crossover fashion, and in nine age- and sex-matched healthy subjects. The bronchial responsiveness to inhaled methacholine was also measured in the same asthmatics on a separate day. Inhaled acetaldehyde caused marked (more than 20%) significant decrease in FEV1 in asthmatics after placebo, which was larger than that in asthmatics after terfenadine and in healthy subjects. There was no significant difference in the decrease in FEV1 between asthmatics treated with terfenadine and healthy subjects. There was a significant correlation between the methacholine and acetaldehyde concentrations producing a 20% fall in FEV1 in asthmatics. We conclude that acetaldehyde causes bronchoconstriction indirectly via histamine release in asthmatics, and that nonspecific bronchial hyperresponsiveness is a necessary precondition for the expression of acetaldehyde-produced bronchoconstriction.
We studied the changes in plasma levels of thrombomodulin (TM) known to be present on vascular endothelial cells and released into circulating blood following damage to endothelial cells, during haemodialysis in 49 patients with end-stage chronic glomerulonephritis maintained on haemodialysis. After a single haemodialysis, plasma levels of TM were significantly elevated from 38.4 +/- 13.8 ng/ml to 46.8 +/- 14.6 ng/ml (p less than 0.05). Plasma levels of TM before haemodialysis were significantly higher in the cases of long-term haemodialysis than in those of short-term haemodialysis (p less than 0.01). From these observations, increased plasma levels of TM may be due to decreased clearance of TM by renal insufficiency, or damage to endothelial cells induced by the recurrent haemodialysis. In those patients with a greater residual blood volume in a dialyser, the changes in plasma levels of thrombin-antithrombin III complex and TM during a single haemodialysis were significantly higher. From these findings, it was suggested that endothelial cell damage is more severe in patients with greater residual blood volume.
A 60-year-old woman on chronic dialysis consulted our department for closer examination of transient atrial fibrillation and a mitral regurgitant murmur. Echocardiography revealed a left atrial abnormal dense echogenic spherical mass, the diameter of which was 2 cm. She died of cerebral bleeding 3 months later. At autopsy, the submitral mass-like structure consisted of light-gray pasty material, which was liquefaction necrosis of a mitral annular calcification. These findings were different from those of the so-called mitral annular calcification found in the elderly or in chronic renal failure patients. The existence of such calcification must be kept in mind and not be mistaken for cardiac tumor.
An autopsy case of dermatomyositis (DM) associated with interstitial pneumonia probably due to cytomegalovirus infection is reported. After corticosteroid therapy for 1 month, a 79-year-old man with DM developed acute respiratory failure due to interstitial pneumonia and died in spite of intensive respiratory care. By polymerase chain reaction method (PCR), DNA of cytomegalovirus (CMV) was detected in the bronchoalveolar lavage fluid (BALF). CMV was also detected by the method of conventional virus culture from BALF. These findings suggested that initial infection or reactivation of CMV had occurred in the lungs. The autopsy specimen revealed the findings of interstitial pneumonia compatible with CMV pneumonitis, but without the presence of intranuclear inclusion bodies. Although the present case of interstitial pneumonia should not strictly be diagnosed as definite CMV pneumonitis without the presence of intranuclear inclusion bodies in the lung tissue, initial infection or reactivation of CMV in the lungs may have contributed to the pathogenesis of interstitial pneumonia. In other cases of collagen vascular disease associated with interstitial pneumonia, CMV or other viruses may contribute to the pathogenesis of interstitial pneumonia.
We evaluated the bronchial hyperresponsiveness to methacholine in the two cases of eosinophilic pneumonia with infiltration of eosinophils into bronchial mucosa. Bronchial responsiveness was not increased in either case in spite of marked infiltration of eosinophils into the bronchial mucosa and submucosa. Hypodense eosinophils are reported in the sputum of patients with bronchial asthma. This suggests that infiltration of activated eosinophils into the bronchial mucosa is an essential factor in bronchial hyperresponsiveness.
The effect of a thromboxane A2 synthetase inhibitor (OKY-046, 400 mg po/day) on mucociliary transport was investigated in 19 asthmatic patients. The nasal clearance time, as measured by the saccharin test, was prolonged in asthmatics (60.2 +/- 8.4 SE min) compared with normal controls (15.1 +/- 3.4 SE min). Within 4 weeks after OKY-046 administration, the nasal clearance time had improved (27.4 +/- 4.4 SE min, P less than .01) and the amount of sputum had decreased 30% (P less than .01). These results indicate that thromboxane A2 plays an important role in mucociliary transport in patients with asthma.
A 25-year-old woman presented with an episode of left calf deep vein thrombosis and pulmonary thrombosis. She was found to have a lupus anticoagulant with anticardiolipin antibodies, some autoimmune antibodies and antibodies for primary Epstein-Barr (EB) virus infection. Six months later, lupus anticoagulant and other autoimmune antibodies were found to be negative and EB virus antibodies were shown to be seroconverted. We suggest that the transient presence of lupus anticoagulant was due to EB virus infection caused by activation of polyclonal B-lymphocytes.