Experiments were conducted in 21 adult mongrel dogs to clarify the effects of Ca-antagonist (nifedipine sublingual administration 2.5mg or 5mg, or nicardipine intravenous administration 30μg/kg or 60μg/kg) on pulmonary blood flow under the condition of collapsed lung on the side of thoracotomy. Under anesthesia, an endotracheal tube with a movable blocker was used to intubate the trachea and the thoracotomized lung was collapsed. Subsequently, a Ca-antagonist was given and the ratio of the left main pulmonary artery/ascending thoracic aorta blood flow was used as an index of hypoxic pulmonary vasoconstriction (HPV). The following results were obtained.
(1) Ca-antagonist administration under lung-collapse on the thoracotomy side resulted in inhibition of HPV of the collapsed lung, whereas, arterial blood oxygen tension (PaO₂) remained in the acceptable range.
(2) The maintenance of the lowered PaO₂ within the acceptable range may have been due to the increase in cardiac output and the elevation of mixed venous blood oxygen tension resulting from Ca-antagonist administration, as well as the residual HPV even after administration of the Ca-angagonist.

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It is well established that alterations of serum thyroid indices frequently occur in nonthyroid disease. The most common finding is a reduced serum T₃ concentration in systemic illness, termed low T₃ syndrome. It is considered that this syndrome is a beneficial adaptation to severe illness and reflects the duration and severity of illness.
We measured serum thyroid hormones, pulmonary functions, and arterial blood gases in 245 patients (mean: 67.0 years) with clinical stable pneumoconiosis, and investigated the relations of thyroid hormones and other measurements. We also investigated the relation of thyroid hormones and radiographic findings. 1) There was a significant correlation between serum level of free T₃ and % VC (p<0.05), and between serum level of free T₃ and FEV_1.0 (p<0.01). 2) There was no apparent correlation between serum level of free T₃ and other pulmonary functions (V₂₅/HT, FEV_1.0%). 3) There was no apparent correlation between serum level of free T₃ and blood gases (PaO₂, PaCO₂ and A-aDO₂). 4) There was no apparent correlation between serum level of free T₃ and radiographic findings. 5) Serum levels of free T₄ and T₄ showed no apparent correlations with other parameters. These results suggest that serum level of free T₃ can be helpful to evaluate the clinical severity in patients with pneumoconiosis.

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We performed unilateral pulmonary arterial occlusion test (UPAO) for the preoperative evaluation of lung function in patients undergoing lung resection. In this test, the main pulmonary artery of either side is occluded to simulate postoperative functional status. In order to evaluate the right ventricular hemodynamic function, we measured right ventricular ejection fraction (RVEF) and right ventricular end-diastolic volume index (RVEDVI) throughout UPAO by thermodilution method. We investigated the relationships between changes in right ventricular hemodynamic function and postoperative complications related to cardiac functions, namely arrhythmias or heart failure. Thirty-four patients without heart disease prior to lung resection were examined by UPAO, and RVEF and RVEDVI were measured. Analyses demonstrated that changes in RVEF were inversely correlated with changes in RVEDVI. In 6 cases, RVEDVI increased from control by over 20% during UPAO. All of these patients had postoperative cardiac complications. The hypothetical ventricular function curves showed a large increase in RVEDVI relative to right ventricular stroke work index (RVSWI), suggesting a decrease in right ventricular function. In conclusion, these results suggest that changes in RVEDVI during UPAO may predict postoperative cardiac complications in patients undergoing pulmonary resection.

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Elevation of the serum IgA level has been observed in many cases of chronic lower respiratory tract infection. To determine the specificity of elevated serum IgA for the pathogen colonizing the respiratory tract of patients, we measured Pseudomonas aeruginosa-specific IgA titers in patients with chronic lower respiratory tract infections by ELISA. Sonicated P. aeruginosa strain BB5746 was used as the coating antigen. Optical density was significantly elevated in sera from patients in whom P. aeruginosa was consistently isolated from sputum cultures, when they were respondent to the antigen, indicating that bacteria-specific IgA is not localized in the respiratory tract surface, but is circulating in the blood stream of these patients. The other two groups, chronic bronchitis patients from whom bacteria other than P. aeruginosa were occasionaly isolated from sputum culture, and IgA nephropathy patients, had no detectable specific IgA in their sera as is the case in normal adults. Our results indicate that bacteria-specific serum IgA levels appearred to correlate with duration from the time of bacterial colonization with P. aeruginosa and the degree of bronchial and alveolar destruction seen on chest X-rays. In addition, detection of increased serum P. aeruginosa-specific IgA seems to contribute to the recognition of persistent bacterial colonization of the respiratory tract.

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We investigated whether or not the inhalation method of beclomethasone dipropionate (BDP) influences patient compliance and the clinical effects of therapy in chronic bronchial asthma, together with a basic study on the lung deposition of BDP using a twin Impinger when various numbers of puffs were discharged into three different spacers (Volumatic, InspirEase, Aerochamber). It was clearly shown that only the spacer, Volumatic maintained a high deposition rate of BDP in the lung model with a dose of 4-puffs/inhalation.
Eighteen chronic asthmatic patients were studied. The patients inhaled BDP (800-1600μg/day) by 1-puff/inhalation using a large spacer, Volumatic, for 12 weeks, and they then inhaled the same dose of BDP as given in the previous period by 4-puffs/inhalation using the spacer for 16 weeks. We compared the compliance of BDP, attack score, %PEFR and frequency of beta-agonist inhalation between these two periods. The compliance of BDP was markedly improved after changing from 1-puff/inhalation (92.8%) to 4-puffs/inhalation (99.8%). In the 4-puffs/inhalation period, attack score and %PEFR were significantly improved as compared to the 1-puff/inhalation period. The frequency of beta-agonist inhalation use in the 4-puffs/inhalation period was significantly lower than that in the 1-puff/inhalation period.
These results indicate that when high dose steroid inhalation is given with a large spacer in chronic asthmatic patients, we should advice them of the appropriate inhalation method in order to obtain good compliance and clinical effects.

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We recently developed a method of proton magnetic resonance spectroscopy (¹H-MRS) to measure the ¹H-MR spectra of peripheral blood lymphocytes (PBL) using only 10⁷ cells. We investigated the clinical feasibility of this method for evaluating disease activities in sarcoidosis and interstitial pneumonitis. PBL was separated from 10ml of venous blood by differential centrifugation with Ficoll-Conray. Using a 90MHz MR spectrometer (EX90, JEOL), the spectrum was obtained with 4000 times accumulation of ¹H signals by single 70 degree pulses at 37°C under spinning. Water signal was suppressed with the homo-gated decoupling sequence. The spectra were analyzed with Gaussian curve fitting. The spectra of patients with active disease showed significant increases in peak heights for (CH₂)_n and CH₃ peaks compared with the control. The peak heights decreased after improvement of disease states. The changes in ¹H-MR spectra suggested activation of PBL in patients with sarcoidosis and interstitial pneumonitis, since similar changes have been shown for cells activated with mitogens. Our preliminary results indicate that ¹H-MRS may be useful to evaluate activation of PBL in sarcoidosis and interstitial pneumonitis.

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We studied the effects of erythromycin (EM) in diffuse panbronchiolitis (DPB) with chronic respiratory failure. Seventeen patients with DPB or sinobronchial syndrome receiving home oxygen therapy (HOT) were treated with EM of 400-600mg/day for twelve months. Five patients discontinued HOT, and hypoxemia was improved in five other patients. Clinical effects were evident at one month after the start of EM administration, and a stable state was achieved after six months of EM therapy. FEV₁ was significantly increased in pulmonary function tests.
Factors which influenced the effects of EM included the period between onset of clinical symptoms and commencement of HOT and/or between commencement of HOT and administration of EM. EM was effective for patients with obstructive, but not constrictive impairment in pulmonary function tests.
These findings indicate that EM is effective for DPB even in patients with chronic respiratory failure.

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Pulmonary cryptococcosis has been considered as a disease associated with depressed immune function of the host. However, it may develop in healthy individuals without any underlying disease. Recently, we experienced three cases of primary pulmonary cryptococcosis.
Case 1. A 30-year-old woman in the sixth week postpartum developed cough and low-grade fever. Chest X-ray showed infiltrative shadows in right S² and left S⁶. A diagnosis of pulmonary cryptococcosis was made from transbronchial brushings and histological examination.
Case 2. A 51-year-old man was noted to have abnormal shadows on chest X-ray film at a regular medical checkup. Chest X-ray examination showed a small nodular density in left S⁹. A diagnosis of pulmonary crytococcosis was made from percutaneous pulmonary paracentesis.
Case 3. A 58-year-old man was noted to have an abnormal shadow on chest X-ray film at a regular medical checkup. Chest X-ray examiantion showed a nodular density in right S⁸. A diagnosis of pulmonary cryptococcosis was made from transbronchial brushings and histological examination.
All three cases showed no impairment in their immune functions. These cases are described with a discussion of the literature.

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To determine whether activations of K-channel and Na-K-ATPase are involved in the action of bronchodilating agents, we studied the effects of various K-channel blockers and ouabain, a Na-K-ATPase inhibitor, on the relaxant responses of canine airway smooth muscle in vitro. Addition of carybdotoxin (ChTx), a Ca-activated potassium channel blocker, and ouabain had no effect on the responses to verapamil and BRL 38227, but inhibited those to salbutamol, forskolin, DBcAMP, and nitroprusside. Apamin, a low-conductance K-channel blocker, and glibenclamide, an ATP-sensitive K-channel blocker, had no effect on the smooth muscle relaxation induced by any agents. The inhibitory effect of ChTx was predominant when the concentration of bronchodilator was low, whereas the effect of ouabain was observed in the presence of a high concentration of bronchodilator. These results suggest that Ca-activated K-channel and Na-K-ATPase may participate in the relaxation induced by bronchodilators that can raise intracellular cyclic nucleotides, and that the contribution of each component differs under different concentrations of the drugs.

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To elucidate the relationship between the clinical manifestations and pathologic findings in pulmonary tumor embolism, we reviewed the autopsy and clinical records of 318 patients who died of various cancers, excluding lung cancer. Sixty-seven (21%) of the patients had at least one tumor embolus in the pulmonary arteries and 12 (3.8%) had multiple tumor emboli contributing to death. We considered that the 12 patients (6 with hepatoma, 3 with gastric cancer, and one each with colon cancer, pelvic cancer, and cervical cancer) had disease defined as pulmonary tumor embolism, and we fully analyzed these cases. Patients with hepatoma had manifestations of submassive pulmonary thromboembolism and patients with other cancers had manifestations of pulmonary microthromboembolism. The lungs of all of the 6 patients with hepatoma had both microscopic and macroscopic tumor emboli and 3 cases were accompanied by pulmonary infarction. On the other hand, the lungs of all of the remaining 6 patients had microscopic (including intracapillary) tumor emboli and 4 cases were accompanied by diffuse alveolar damage. The lung of 1 of the patients with hepatoma and 2 of the patients with other cancers also had pulmonary tumor thrombotic microangiopathy. In patients with hepatoma, the tumor emboli seemed to be derived from tumor invasion to large veins, while the tumor emboli seemed to be derived from widespread tumor invasion to lymphatic channels in the remaining patients. The authors conclude that pulmonary tumor embolism shows heterogeneous manifestations such as acute and subacute cor pulmonale and diffuse alveolar damage. Clinicians should keep in mind that the heterogeneity of the disease is closely associated with the varieties of malignancies and their spread.

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We compared lung fibroblast growth-stimulating activity (FGA) of several serine proteases including thrombin in vitro, and examined the mechanism of FGA. FGA was measured by incorporation of ³H-thymidine into lung fibroblasts (IMR-90). The activities of the enzymes were measured by spectrofluorometric method with synthetic peptides specific for each enzyme, and these enzymes were added to the assay system for FGA at concentrations of 7×10₀-7×10⁵unit/ml.
Human thrombin, bovine trypsin and bovine α-chymotrypsin showed clear FGA, but that of α-chymotrypsin was lower than those of thrombin and trypsin. On the other hand, porcine pancreatic elastase and human neutrophil elastase did not show any FGA, and had a cytotoxic effect on fibroblasts.
A specific low molecular-weight thrombin inhibitor, argatroban (MW. 562), inhibited not only the enzyme (peptidolytic) activity of thrombin, but also its FGA at the same concentration. These results suggest that serine proteases can be classified into at least two groups, showing FGA and cytotoxic activity, respectively, and that the FGA of the former group is mediated by their catalytic (enzymatic) action.

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A 15-year-old woman presented with an abnormal chest X-ray taken at a medical check up. Her chest X-ray disclosed multiple nodular shadows in bilateral lung fields. A transbronchial biopsy was non-diagnostic and an open biopsy was performed. The tumor was histologically diagnosed as epitheliod hemangioendothelioma on the basis of associated with immunoreactivity to factor-VIII related antigen by immunohistochemistry and the presence of Weibel-Pallade bodies on electron microscopy. She has been followed-up in her home town without significant change.

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A 65-year-old woman was admitted to our hospital because of pulmonary nodules, about 3cm in diameter in the right upper lobe accompanied by pleural indentation, and 5mm in diameter in the left middle lung field, revealed by chest X-ray. She had no clinical signs or symptoms except achalasia-like discomfort swallowing. Results of physical examinations were within normal limits. A specimen obtained from the nodule in right S² by transbronchial biopsy showed noncaseating epithelioid granuloma containing asteroid bodies, and negative staining for acid-fast bacilli. No malignant cells were found in the specimen. Bacteriological examination of a bronchial lavage specimen was negative for pyogenic bacteria, mycobacteria and fungi. A PPD skin test was negative. BALF revealed an increase of lymphocytes and elevation of CD4/CD8 ratio. Fifteen years previously, the patient had been diagnosed as having sarcoidosis by scalene node biosy, and had been treated with steroid therapy. Pulmonary nodules associated with pleural indentation in sarcoidosis is relatively rare, and is usually due to malignancy such as lung cancer. This possibility was ruled out clinically in the present case. Therefore, it was concluded that the pulmonary nodules in this case were due to the sarcoidosis itself.

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A 50-year-old male spray paint worker was admitted with non-productive cough and dyspnea on exertion. Chest X-ray and chest CT showed diffuse interstitial shadows in the bilateral lung fields. After admission, the symptoms and chest X-ray findings improved over several days, and he was followed as an outpatient. He then developed nocturnal dyspnea with wheezing and dry cough every day. About two months later, chest X-ray showed more severe diffuse interstitial shadows which did not disappear after admission. Bonchoalveolar lavage and transbronchial lung biopsy revealed allergic exudative interstitial pneumonia, and he was treated with steroid therapy. Paint contains toluene diisocyanate, and challenge test to toluene dissocyanate was positive. In the early course, this case presented with bronchoconstriction; bronchial reversibility and bronchial hyperresponsiveness to methacholine were positive. Bronchoconstriction may cause worsening of respiratory symptoms in patients with hypersensitivity pneumonitis induced by isocyanates.

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A 69-year-old female was admitted for the evaluation of chronic persistent cough of about six week duration which was particulary worse at night and did not respond to antibiotics or cough medicines. She did not smoke and had no history of allergies or abnormal inhalations. Eosinophil counts, serum IgE, CRP, titers of cold hemagglutinin (CHA), and antibody to mycoplasma were all within normal ranges. Chest X-ray films and respiratory function tests showed no abnormalities. Because of her complaint of mild heartburn, gastroesophageal reflux (GER) was thought to be a possible cause of her chronic cough. Upper gastrointestinal X-ray films revealed barium reflux up to the cervical esophagus, and gastrointestinal fiberscopy showed reflux esophagitis. Bronchial biopsy specimens taken by fiberoptic bronchoscopy showed chronic inflammatory changes of bronchial mucosa with focal squamous metaplasia, mucosal basement membrane thickening, and lymphocytic infiltration in the submucosa. She made favorable progress following treatment with a histamine H₂ blocker and cisapride for six weeks. She met Irwin's criteria and we concluded that her cough was caused by GER. We speculate that repeated tracheobronchial microaspirations of refluxed gastric acid may cause chronic inflammatory changes of the bronchial mucosa resulting in persistent cough.

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We report a case of interferon-α-induced pneumonitis. A 61-year-old man was diagnosed as having recurrence of renal cell carcinoma and treated with 3×10⁶ unit of interferon-α daily for 8 weeks. On the 55th injection, he presented with a high fever and mild dyspnea, and his chest CT films revealed diffuse reticulonodular shadows in both lung fields. We suspected interstitial pneumonitis due to interferon-α, and started steroid therapy. He showed rapid improvement of symptoms and diffusing capacity, and the pulmonary infitrates in his chest CT were markedly reduced. Transbronchial lung biopsy (TBLB) revealed slightly thickened alveolar walls and small granulomatous-like lesions. These granulomatous-like lesions showed marked accumulation of macrophages. To our knowledge, this is the first report of interferon-α-induced pulmonary injury in Japan

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Case 1 was a 75-year-old woman. Her chest X-ray showed a 3cm solitary nodule in the right S4, and biopsy obtained by fiberoptic bronchoscopy revealed epithelioid cell granuloma. Four weeks later, Mycobacterium avium complex (MAC) was detected on culture of the bronchial lavage fluid. She was treated with INH, RFP and EB for 12 months and recovered with no relapse.
Case 2 was a 75-year-old man with mild diabetes mellitus and hypertension. Chest X-ray showed a 4cm solitary nodule in the right S9. Percutaneous pulmonary aspiration revealed numerous acid-fast bacilli on smear, and he was treated with INH, RFP and EB. Culture proved M. avium complex. The patient was unable to continue his medications because of gastrointestinal side effects, so right lower lobectomy was performed.
Cases of M. avium complex infection presenting as solitary pulmonary nodule are very rare. We found only 12 reported cases in Japan and in other countries. The most usual site of cavitary lesions in M. avium complex infections is both upper lobes, in contrast to the relatively even distribution of solitary pulmonary nodules of the 14 cases (12 reported cases and our 2 cases).

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A 61-year-old female was admitted to our hospital because of cough, hemosputum and right chest pain. The P-A and L-R chest films revealed focal consolidation in the right upper filed and mass-like shadow in the right S³. Transbronchial lung biopsy specimens showed collections of lipid-laden macrophages. The lipid material of macrophages in broncholaveolar lavage fluid was stained yellow-orange with Sudan IV. The patient had no difficulty in swallowing and had no history of regular use of oily drugs. Fiberoptic bronchoscopy and chest CT showed no obstruction of bronchi. She had used much domestic insecticide with the doors closed before going to bed every summer and autumn for 10 years. We concluded that the domestic insecticide containing mineral oil had resulted in exogenous lipiod pneumonia. Her symptoms and abnormal shadows in chest X-ray film disappeared soon after antimicrobial chemotherapy was started. She is now healthy without recurrence.

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We report a case of pneumonitis induced by tolfenamic acid. A 23-year-old woman was admitted to our hospital because of cough and fever. She had been treated with tolfenamic acid and other medications for lumbago. Nine days after the treatment, she developed erythema, fever, cough and dyspnea. Her chest X-ray revealed multiple patchy and micronodular shadows in both lung fields. Bronchoalveolar lavage fluid (BALF) showed increased total cells, lymphocytes, eosinophils and CD4/CD8 ratio. Microscopic examination of transbronchial lung biopsy (TBLB) specimens showed infiltration of mononuclear cells and eosinophils into the alveolar wall and the interstitium. After discontinuation of all drugs, her complaints, laboratory data and chest X-ray findings markedly improved. The lymphocyte stimulation test (LST) and challenge test for tolfenamic acid were positive. Based on these findings, we diagnosed this case as pneumonitis (eosinophilic pneumonia) due to tolfenamic acid. To our knowledge, there has been no reported case of pneumonitis due to this drug in Japan.

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A 57-year-old man with pulmonary tuberculosis underwent left upper lobectomy in 1984. In 1987, chest X-ray showed a fungus ball, and Aspergillus species was isolated from sputum. He was treated by intracavitary injection of amphotericin B (AMPH) in June, 1992. However, no change was observed in the chest CT scan after a total dose of 1, 000mg of AMPH. Combination therapy of intravenous administration of 100, 000 units of urinastatin and intracavitary injection of AMPH resulted in complete disappearance of the fungus ball on chest CT scan. This report describes case of pulmonary aspergilloma successfully treated with the combination of AMPH and urinastatin.

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A 64-year-old male was admitted to our hospital with dyspnea and high fever. The patient had a relative bradycardia and severe hypoxemia. Velcr rales were heard throughout the entire lung fields. Leucocytosis was absent. Chest X-ray showed bilateral diffuse reticular shadows. Corticosteroid pulse therapy and minocycline were introduced on the suspicion of either idiopathic interstitial pneumonia or Chlamydial pneumonia. Subsequently, his symptoms gradually improved. Although the patient had no history of exposure to birds, the titer of complement fixation test for Chlamydia was 1:32 during the acute illness. Microplate immunofluorescence antibody technique proved infection with Chlamydia pneumoniae. We consider this is a rare case of severe pneumonia caused by C. pneumoniae.

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A 27-year-old female presented to our hospital because of anterior chest pain and left cervical tumor. Her chest X-ray film showed bilateral swelling of the superior mediastinum, which was composed of multiple mediastinal masses with obliteration of adjacent mediastinal fat on chest CT film. A specimen obtained from a left cervical lymph node histologically showed granuloma formation with central caseous necrosis, and the diagnosis of cervico-mediastinal tuberculous lymphadenitis was therefore made. Both cervical tumor and mediastinal masses decreased in size following antituberculous chemotherapy.
Mediastinal tuberculous lymphadenitis in young adults is rare. It is difficult to differentiate this condition from other mediastinal tumors, although its CT findings are characteristic.

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