Crackles were recorded with one of two systems in a total of 58 cases and compared. In one system a stethoscope was attached to a microphone; in the other system no stethoscope was used (see reference 9). Coarse crackles were recorded with the stethoscope system in 11 patients, and with the microphoneonly system in 12 patients. Most patients with coarse crackles had bronchiectasis. Fine crackles were recorded with the stethoscope system in 13 patients, and with the microphone-only system in 22 patients. Most patients with fine crackles had idiopathic pulmonary fibrosis. Each record was examined visually, and all crackles recorded during one inspiration were selected. Power spectra were estimated with the maximum entropy method and peak frequencies were determined with the damped least-squares method. Type-I crackles were defined as those with all peak frequencies below 800Hz; these low-pitched sounds may correspond to coarse crackles. Type-II crackles were defined as those with peak frequencies over 800Hz regardless of the existence of peaks below 800Hz; these high-pitched sound may correspond to fine crackles. The “%Type II” was defined as the percentage of the total crackles that were Type-II crackles.
The %Type II value among coarse crackles was 10 ± 16% with the stethoscope and 3 ± 7% with the microphone. Among fine crackles, the values were 65 ± 22% with the stethoscope and 79 ± 23% with the microphone. For both kinds of equipment, the %Type II differed significantly between coarse and fine creackles (p<0.01).
The stethoscope-transmitted sound had components that could be used to differentiate fine crackles from coarse crackles. For clinical purposes, crackles recorded with a stethoscope are as useful as those recorded with a microphone only.

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The c-myc and p53 genes are thought to be an oncogene and a tumor suppressor gene, respectively. These genes' products are characteristic of malignant tumors. We quantitatively analyzed the c-myc and p53 products by flow cytometry in two cases of pulmonary sclerosing hemangioma. In case 1, 32.3% of the tumor cells were found to have the c-myc product, and 8.9% were found to have the p53 product. In case 2, 6.7% of the tumor cells were found to have the c-myc product and 15.5% were found to have the p53 product. The percentages in both cases were twice as high as those in a negative control lymphocytes stained with c-myc and p53 products. Therefore, these two cases showed positive expression of the c-myc and p53 products.
In addition DNA from six other patients with sclerosing hemangioma was analyzed with paraffinembedded sections. All six had DNA diploidy, with DNA indexes ranging from 0.91 to 1.03 and coefficients of variation ranging from 3.0 to 5.5. We suggest that pulmonary sclerosing hemangioma is a very weakly malignant tumor.

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Periodic breathing (PB) during sleep at an altitude of 5100m was studied with a pulse oximeter. The subjects were six Japanese who stayed at about 5100m (group A), nine Japanese who climbed above 7000m (group B) and eight Sherpase (high lancers). Among Japanese subjects, PB was observed most often in group A. The sherpas almost never breathed periodically. PB and symptoms of acute mountain sickness correlated positively among Japanese subjects. The cycle time of PB did not differ among the three groups. PB may be related to acclimatization.

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We encountered five cases of drug-induced pneumonitis due to Sho-saiko-to or interferon-α or both. In all 5 cases the underlying disease was chronic hepatitis or liver cirrhosis caused by hepatitis C virus.
Interferon-α alone was administered in one case, Sho-saiko-to alone was administered in two cases, and both were administered in two cases. Bronchoalveolar lavage was done in 4 cases. In three cases, lymphocytosis and abnormally low CD4/8 ratios were found on examination of bronchoalveolar lavage fluid. In the only case in which interferon-α alone was given the percentage of neutrophils in bronchoalveolar lavage fluid was abnormally high, and the adult respiratory distress syndrome developed. Lymphocyte stimulation tests were done in four cases, and in all four cases the only positive results were against Sho-saiko-to or against interferon-α. The frequency of drug-induced pneumonitis among patients with chronic hepatitis or liver cirrhosis was 0.7% in those given only Sho-saiko-to, 0.5% in those given only interferon-α, and 4.0% in those given both interferon-α and Sho-saiko-to. Therefore, pneumonitis due to Sho-saiko-to and to interferon-α is more likely to occur if these two drugs are given simultaneously.

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An early phase II clinical study was done to investigate the activity and the safety of oral administration of etoposide for 21 consecutive days in patients with non-small-cell lung cancer. An interim analysis was done after registration of 24 cases. One case was a dropout because of an insufficient administration period (4 days). The other 23 cases were complete: they comprised 9 cases of adenocarcinoma, 13 cases of squamous cell carcinoma, and 1 case of large cell carcinoma. Prior therapy had not been given in two cases. The doses used were 50mg/person/day in 12 cases and 75mg/person/day in 11 cases. The response observed was one case of at 50mg/person/day to stage IV squamous cell carcinoma, 17 cases were no change, 5 cases were progressing disease, and giving a response rate of 4.3% in complete cases. Considering those results, we decided that it would be difficult to achieve a 20% response rate by the end of this study, and therefore the study was terminated. The side effects of the regimen were tolerable. In conclusion, etoposide was not active against non-small-cell lung cancer at the dosage and schedule employed. Further investigation is required to obtain a more effective form of therapy.

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We studied the clinical features of 17 Japanese patients with pulmonary eosinophilic granuloma. Fourteen of the patients were men and three were women; they ranged in age from 19 to 64 years, with a mean of 34 years at the time of the first examination. Pathologic diagnosis in all patients was based on histologic findings of specimens obtained by open lung biopsy.
Major symptoms were dry or productive cough, chest pain, dyspnea, and fever; 23.3% of the patients were asymptomatic. Five patients had pneumothorax. Most patients did not have abnormal physical signs. All 17 patients had histories of smoking, and 14 had started to smoke cigaretts before the age of 20 years.
Ten patients (58.8%) first presented with cough or dyspnea, and in the other patients (41.2%) the first abnormalities detected were pulmonary infiltrates on chest radiographs during health examinations.
Chest roentgenograms usually showed bilateral abnormalities. These abnormalities were distributed over all lung fields in 9 cases (52.9%), in the upper and middle lung fields in 4 cases (23.5%) in the upper lung fields in 3 cases (17.7%), and in the middle lung fields in 1 case (5.9%). Micronodular, reticular, cystic or linear shadows were evident in most cases, and were mixed in various proportions. Eleven patients (65%) had abnormalities of pulmonary function. Low %VC and %FEV₁ and high RV/TLC ratios were observed in 20-40% of the patients. Low DLCOs (%DLCO<70%) were observed in 53% of the patients. Arterial blood gases were normal in 11 of 15 patients.
The extent of shadows in the chest roentgenogram was related to the frequency of dyspnea, to the total number of cells in bronchoalveolar lavage fluid, and to the abnormally low %FVC and %FEV₁ but not to the % DLCO.
Data from bronchoalvealor lavage fluid were non-specific in this disease, but further studies will be needed.
Follow-up data were collected on 16 patientss. The mean time from the histologic diagnosis after open lung biopsy to the last observation was 81.8 ± 45.1 months (range, 2 months to 15 years). One patient died of pulmonary eosinophilic granuloma. The usefullness of steroid therapy remains uncertain.

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Maximal Inspiratory pressure (MIP) and maximal expiratory pressure (MEP) were measured long after lung resection with reference to operative procedure and vital capacity (VC). MIP and MEP were measured before surgery and 3 months after surgery in 80 patients who underwent lung resection. The procedures were pneumonectomy in 4 cases, lobectomy in 42 cases, segmentectomy in 3 cases, and wedge resection in 31 cases. Postoperative MIP, MEP, and VC were expressed and analyzed as percents of their respective preoperative values (MIP (%), MEP (%), VC (%)). Patients who underwent lobectomy had significantly lower MIP (%) and MEP (%) than did those who underwent wedge resection (p<0.001). Both MIP(%) and MEP (%) correlated significantly with VC (%) (p<0.001).
Pulmonary resection can continue to affect both pulmonary function and respiratory muscle strength even 3 months after surgery.

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High doses of inhaled beclomethasone dipropionate (BDP) are effective in some patients wich chronic obstructive pulmonary disease (COPD). However, dose-response data for this agent are limited. To determine whether patients receive maximum benefit from 1600μg of BDP, we performed a radomized, double-blind, placebo-controlled, cross-over trial. Twenty-one patients with stable COPD [mean±SD: age, 69.1±6.8yrs; FEV₁, 0.86±0.28L] were treated with both inhaled bronchodilators and 1600μg of BDP daily for at least 3 months. Each patient received 30mg of oral prednisolone or a placebo for 3 weeks. In addition to end-point spirometric assessments daily peak expiratory flow rate, symptom scores, and scores on a chronic respiratory disease questionnaire were recorded for the last week of each 3-week period. Oral prednisolone did not improve FEV₁, FVC, symptoms or scores on the questionnaire. We conclude that 1600μg of BDP in addition to inhaled bronchodilators produces maximal improvements in stable patients with COPD.

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The effect of clarithromycin on symptoms and on mucociliary transport (as assessed by the saccharin test) were studied in 32 patients with sino-bronchial syndrome. Before treatment with clarithromycin, the nasal clearance time was significantly longer in these patients (70.3 ± 64.7min, mean ± SD) than in control subjects (11.9 ± 5.3min, p<0.001). By the end of 4 weeks of treatment with oral clarithromycin (400mg/day), nasal clearance time in the patients had improved significantly (30.4 ± 39.5min, p<0.001). Before clarithromycin therapy, bacteria were found in cultures of sputum from 15 patients. After clarithromycin therapy, bacteria were found in cultures of sputum from only 3 of those 15 patients. Cough frequency, volume of sputum, and dyspnea on exertion were significantly improved by clarithromycin therapy. These findings suggest that mucociliary transport is abnormal in patients with sino-bronchial syndrome, and that clarithromycin can be clinically useful in these patients.

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We encountered five patients with Swyer-James syndrome. All were men, and ranged in age from 20 to 70 years (mean, 41 years). Their chest X-ray films showed left unilateral hyperlucency. Examinations revealed bilateral involvement in 3 cases and irregularity of involved regions in 2 cases. Chest CT scans revealed the distribution and severity of affected regions in greater detail than did other radiologic exams. Delayed clearance of xenon is a sign of air trapping, which is characteristics of this syndrome. Thus, ¹³³Xe inhalation scintigrams were useful to detect air trapping, especially when mediastinal shift was not apparent on chest X-ray films. Bronchial damage is believed to cause this syndrome, and the present findings support this view. It is noteworthy that all five of these patients were men, and that in all five the affected lung was on the left. Moreover, although “respiratory tract infection is considered to be a very important” factor, many patients had no history of airway infection in childhood. Thus, some congenital factor or factors may contribute to the development of this syndrome.

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Pulmonary hypertension caused by acute pulmonary embolism has been attributed to mechanical obstruction of the pulmonary arteries and also to vasoconstriction. We examined the role of nitric oxide in the vasoreactivity associated with pulmonary microembolism. Two kinds of microemboli of similar size were used: thorny microemboli (lycopodium spores, LP) and smooth microemboli (latex microspheres, MS). In isolated rat lungs perfused with blood, five injections of LP or MS into the pulmonary artery each caused a rapid increase in mean perfusion pressure, followed by a slow fall to a new, higher base line. Vasoconstriction was significantly greater after embolization with LP than after embolization with MS. Preadministration of L-NMMA, a nitric oxide synthase inhibitor, enhanced the increase in mean perfusion pressure caused by embolization with LP, but not the increase caused by embolization with MS. Before embolization, acetylcholine caused slight vasodilation. After embolization with MS, acetylcholine caused vasodilation; but after embolization with LP, acetylcholine caused vasoconstriction.
Thus, we conclude that repeated embolization with LP may cause endothelial injury, and that nitric oxide may protect against pulmonary hypertension induced by LP emboli.

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Monocrotaline (MCT) causes lung inflammation and right ventricular hypertrophy associated with lung vascular thickening in rats. We hypothesized that peptide leukotrienes play a role in MCT-induced lung disease, and examined the effect of ONO 1078, a specific antagonist of LTC4, D4 and E4 receptors on MCT-induced right ventricular hypertrophy and on lung vascular thickening. Next, we measured leukotriene C4 (LTC4) levels in the lung tissue of MCT-treated rats. Within 3 weeks after the injection MCT had caused an increase in the ratio of right ventricular weight to left ventricle + septum weight (RV/(LV+S)) and an increase in media wall thickness of the muscular arteries of the lung. In rats given both ONO 1078 and MCT, these changes were significantly less severe than in rats given MCT only. The LTC4 levels in MCT-treated rats were significantly higher than in saline-treated control rats. These results indicate that this antagonist of peptide leukotriene receptors inhibits right ventricular hypertrophy induced by MCT, and suggest a role for peptide leukotrienes in the inflammatory process that contributes to lung vascular remodeling in MCT-treated rats.

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We studied morphologic and morphometric characteristics of the bronchial walls in lungs obtained at autopsy form elderly patients who had had bronchial asthma. Thirteen patients (age at time of death 57 to 98 years; average, 81 years) were divided into three groups: AS, died of severe astham attack (n=4); AC, admitted with asthma symptoms but died of other diseases (n=6); and NA, died of other diseases and had had no asthma symptoms in the year before death (n=3). Lungs from ten non-smokers with no history of bronchial asthma or other lung disorders were used as control. Transverse sections of segmental and subsegmental bronchi were prepared, and four quantities were analyzed: 1) the ratio of total bronchial gland area to total area of the bronchial wall (Yamanaka index), 2) the thickness of the basement membrane, 3) the thickness of the smooth muscle bundle, and 4) the ratio of luminal area to total area of the bronchial wall (bronchial dilation ratio). In the AS group, the Yamanaka index and the thickness of the smooth muscle bundles and of the basement membrane were significantly greater than those in the control group at both the segmental and subsegmental levels, with massive eosinophil infiltration into the bronchial walls. Furthermore the bronchial dilation ratio at the subsegmental level correlated closely with the Yamanaka index. Thickness of the smooth muscle bundle seemed to be most representative of the severity of asthma symptoms. In conclusion, morphometric findings of bronchial walls in elderly patients with asthma symptoms seem to be similar to those in their younger counterparts.

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A 35-year-old man was admitted with fever and right-sided chest pain. A chest X-ray film showed an apple-sized mass shadow in the right lower lobe and minimal pleural effusion Cryptococcus neoformans was identified by culture of the pleural effusion. Transbronchial lung biopsy was done, and pulmonary cryptococcosis was diagnosed. The patient's condition improved after treatment with fluconazole and miconazole. Two months after discharge he was readmitted with a massive ipsilateral pleural effusion. The serum cryptococcal antigen titer was almost normal, and examination of the effusion for crypptococcal antigen was negative. The effusion resolved with thoracic drainage and administration of imipenem. The second effusion was believed to have resulted not from cryptococcosis, but from another bacterial infectin. This case indicates that determination of cryptococcal antigen in serum is useful for diagnosis of pleural effusion and for monitoring pulmonary cryptococcosis.
Clinical studies of five patients with pulmonary cryptococcosis indicated that symptoms and abnormal laboratory data were positive only in those with rather large lesions. In all cases the diagnosis was made after transbronchial lung biopsy, and treatment with antifungal agents including fluconazole was successful.

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Varicella pneumonia is a rare but serious and occasionally fatal complication of infection with varicellazoster. A 40-year-old man was admitted to our hospital with fever, eruptions, dyspnea, and severe hypoxemia. A chest X-ray film showed diffuse nodular infiltrative shadows in both lung fields. Transbronchial lung biopsy was done, and examination of the specimen revealed an organizing exudative reaction in the alveolar spaces, as well as interstitial inflammation.
Primary varicella pneumonia was diagnosed on the basis of family history, typical eruptions, high titer of antibody against varicellazoster virus, and pathological findings. The patient was treated with methylprednisolone, antibiotics, acyclovir, and immunoglobulin. The skin eruptions and disturbances of gas exchange and diffusion resolved in about one week, but the infiltrative shadows on chest X-ray films remained for more than eight weeks.

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A 64-year-old woman was admitted to our hospital with a hemothorax after one year of therapy for angiosarcoma that had arisen from the skin of the head. The hemothorax was believed to have resulted from metastasis of the angiosarcoma. Interleukin-2 (IL-2) at a dose of 20×10⁴ U once daily was administered intrapleurally. Clinical improvement was first observed on the second day after the first dose of IL-2. Increases in natural and in lymphokine-activated killer activity of lymphocytes in pleural effusion were found on the eighth day. Starting on the 16th day of IL-2 therapy, no more fluid was drained, so administration of IL-2 was stopped. The clinical coutrse indicated that the pleural effusion disappeared not because of pleurodesis but because of the anti-cancer effects of IL-2. There were no marked side effects, and Intrapleural administration of IL-2 may be useful in patients with hemothorax due to metastasis of angiosarcoma.

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A 45-year-old man with Alport's syndrome presented with chest pain and dry coughing. A chest roentgenogram showed bilateral simultaneous spontaneous pneumothoraces. Possible causes such as pulmonary bullae were not detected. A partial defect in type IV collagen, which is involved in repair of the basement membrane, may have played a role in the etiology of pneumothoraces in this patient.

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A 47-year-old woman was admitted to our hospital because of two episodes of right pneumothorax. After continuous suction through a thoracic drain, a computerized tomographic scan showed that air was still trapped between lung lobes. Video-assissted thoracic surgery revealed a bulla on the visceral pleural of the upper lobe (S2) and several dark-red spots and white-coated lesions surrounding a defect of the diaphragm. The involved portions of the diaphragm and of the lung were excised. Microscopic examination of the excised specimens showed endometriosis. Catamenial pneumothorax may be caused by intrathoracic endometriosis, but very few cases in which pulmonary or visceral pleural endometriosis was demonstrated histologically have been reported.

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A 65-year-old woman was referred to our department because of an abnormal shadow on the chest roentgenogram. The chest roentgenogram showed infiltrative shadows in the right middle and lower lung fields. The chest CT scan showed non-segmental infiltration with a hazy margin and a clear air bronchogram in the right S⁸ area. A transbronchial aspiration cytology specimen showed atypical lymphocytes, and a transbrochial lung biopsy specimen showed infiltration by atypical lymphocytes. Malignant lymphoma was suspected from the results of the biopsy examination, and a right middle and lower lobectomy was done. The pathological findings showed proliferative atypical lymphocytes in the alveolar and interstitial areas. Malignant lymphoma (diffuse medium cell type by LSG classification) was diagnosed and an immunohistiochemical examination showed monoclonal proliferation of T lymphocytes, which were positive for T lymphocyte surface marker (UCHL-1). Therefore, we believe this was a case of primary pulmonary malignant lymphoma of the T-cell type.

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A 55-year-old man was admitted to the International Medical Center of Japan because of obstructive pneumonia in the the right middle and lower lobes. His left kidney had been removed 3 years earlier because of renal cell carcinoma. Metastatic lung cancer from renal cell carcinoma was diagnosed. Bronchial artery embolization was done twice with sponges, because the tumor was thought to be resistant to interferon. Three days after the second embolization, the tumor was removed through the trachea, and atelectasis was relieved. Bronchial artery embolization may be useful for treatment of metastatic lung cancer from renal cell carcinoma.

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Pneumocystis carinii pneumonia is the most common respiratory infection in patients with the acquired immunodeficiency syndrome, and inhalation of pentamidine aerosol is currently used for secondary prophylaxis.
A 16-year-old patient with hemophilia A and the acquired immunodeficiency syndrome had a spontaneous pneumothorax during inhalation of pentamidine aerosol for secondary prophylaxis of Pneumocystis carinii pneumonia. Tube thoracostomy and pleurodesis were done without success. Thoracotomy was done 27 days after admission. The patient tolerated the procedure well, and the postoperative course was uneventful. Grocott staining of tissue from the bronchopleural fistula revealed Pneumocystis carinii, which suggests that the pentamidine aerosol failed to control and active Pneumocystis infection in peripheral lung zones.

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A 67-year-old man with pulmonary emphysema was admitted to the hospital because of left back pain. Chest roentgenography revealed an infiltrate in the left upper lobe, with cavitation, Mycetoma-like shadows were seen in the cavities about 3 weeks later, and a test for the precipitating antibody to Aspergillus fumigatys was positive. Chronic necrotizing pulmonary aspergillosis (CNPA) was diagnosed, and fluconazole was given. A chest roentgenogram taken 4 weeks later showed resolution of both the mycetoma-like shadows and much of the infiltrate. Systemic immunosuppression was highly unlikely: the patient had not been undergoing corticosteroid therapy, and had no predisposing conditions, such as a chronic debilitating illness or diabetes mellitus. In that sense, this case is similar to another reported recently, in which CNPA was associated with chronic obstructive pulmonary disease in an immunocompentent patient.

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Helical CT was used on a trial basis for secondary screening of lung cancer, and its clinical usefulness is discussed in this report. The subjects 157 patients with abnormal shadows on plain chest X-ray images acquired between November 1993 and August 1994. Imaging parameters used for screening CT were as follows: 50mA, 120kV, a couch-top movement speed of 20mm/s, and a beam width of 10mm. The entire lung field was scanned during a single breath-hold. Reconstructed images were generated at 10-mm intervals by the 180° interpolation method, and films were produced. Images of the entire lung field were made during a single breath-hold in all patients. Abnormal shadows were detected in 73 of 157 patients by screening CT. These 73 patients included 14 with lung cancer, 53 with benign lesions, one under observation, and five others. The average diameter of the tumors was 11.1mm.
The lung cancers detected all arose in the periphery, and were classified into stage I (10 paeitents), stage IIIA (3 patients), and stage IV with bone metastases (1 patient). Lung cancers in clinical stage I (3 patients) and stage IV (1 patient) were difficult to see on plain chest X-ray films.
We conclude that screening CT is useful for early diagnosis of lung cancer because the entire lung field can be imaged during a single breath-hold. Therefore, helical CT can be expected to be useful in screening for lung cancer.

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