To evaluate the usefulness of nifedipine for the treatment of pulmonary hypertension, the effects of nifedipine on pulmonary hemodynamics and gas exchange were studied in 36 patients with chronic pulmonary disease.
The patients were divided into two groups. Non PH group: 18 patients with pulmonary arterial mean pressure (Ppa)<20 Torr. PH group: 18 patients with Ppa≥20 Torr. Cardiac catheterization was performed with a Swan-Ganz catheter and cardiac output was measured by the thermodilution method. The femoral artery was cannulated with a lung water catheter for blood gas sampling and pressure monitoring, and pulmonary extravascular thermal volume (ETV) was measured by the double indicator dilution method using heat and dye.
After baseline hemodynamic and gas exchange measurements were made, the patients were given 10mg of nifedipine sublingually, and after 20min, the same measurements were repeated and compared with the changes after 100% oxygen inhalation.
After administration of nifedipine, C. I. increased and Pao and total peripheral vascular resistance had fallen significantly in both groups, but Ppa was almost unchanged and pulmonary arteriolar resistance (PAR) had fallen significantly only in the PH group. PaO₂ decreased but PvO₂ and O₂ transport increased in both groups. In the nonPH group, the ETV was unchanged, but in the PH group, it significantly increased from 6.76±0.47 to 7.46±0.35ml/kg.
The PAR change after nifedipine showed significant correlation with that after 100% oxygen inhalation (r=0.73), so, it was suggested that nifedipine inhibits hypoxic pulmonary vascoconstriction. In addition, the PAR change after nifedipine showed significant correlation with baseline PAR value (r=0.89).
Therefore, nifedipine was thought to be useful for vasodilator therapy in chronic pulmonary disease with pulmonary hypertension.

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In 12 dogs allotransplantation of the left lung was carried out and postoperatively the pulmonary artery occlusion test (PA-occlusion test) was performed serially for the evaluation of the hemodynamic function of the transplanted lung. Six dogs survived 14 days and were sacrificed for macroscopic and microscopic investigations. The mean pulmonary artery pressure (MPA-P) after the occlusion of the right pulmonary artery elevated just after the left lung transplantation, over two times as compared with the control MPA-P.
On the postoperative second day the MPA-P decreased moderately and on the 7th day all PA pressures fell. On the 14th postoperative day the MPA-P after the occlusion of the opposite, unilateral pulmonary artery showed a gradient in 5 dogs in which the macroscopic formation of thrombus at pulmonary vein around the anastomosis or rejection were observed under light microscopy.
Therefore it was considered that in the successful allotransplantation without thrombosis and rejection the PA pressure shoud remain continuously at a low level for one week postoperatively. We would like to emphasize that the PA-occlusion test may be a good monitoring examination for the detection of operative defect or rejection after the transplantation.

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Pulmonary lesions in experimental recurrent pulmonary thromboembolism were examined to consider the pathogenesis of thromboembolic pulmonary hypertension. Sliced fresh autologous artificial thrombi were infused into the marginal ear vein of 42 rabbits once every 2 weeks, 4 times in toto for 8 weeks to produce lesions. These rabbits were sacrificed to examine the respective morphological changes in the lungs, 1, 2 weeks, 1, 2 and 3 months after the final infusion of thrombus. Pulmonary arterial pressure and the ratio of cardiac hypertrophy were measured under open chest surgery in 26 rabbits (9 of those were from the group of 1 week, 8 from the group 1 month and 9 from the group 3 months after the final infusion).
One to 2 weeks after the final infusion of thrombis thromboembolic arteritis occurred in the small pulmonary artery plugged with organized thrombi. In the non-embolized small artery, on the other hand, the lumen became markedly narrowed due to the circumferential intimal fibrosis in the wall. Although inflammatory changes in the arterial wall had disappeared at 1 month, the circumferential fibrosis further increased in degree, leading to almost complete obstruction of the lumen in a small number of arteries. Moreover, a large number of excrescences were formed in the outermost medial smooth muscle cells. Fibrous thickening appeared in the intima of small artery at 3 months, but narrowing of the vascular lumen became mild in degree. No plexiform lesion occurred in the artery. At 1 week and 1 month, the mean pressure value of pulmonary arteries had gradually arisen to 13.20±3.25mmHg and 15.40±3.25mmHg, respectively, when the hearts showed mild right hypertrophy. At 3 months, however, the pressure value decreased to 12.21±1.08mmHg close to the control level (Control; 11.50±1.47mmHg). Therefore, pulmonary hypertension induced by recurrent pulmonary thromboembolism is a reversible change.
In experimental recurrent pulmonary thromboembolism in rabbits, the author, therefore, considers that the major role in the pathogenesis of pulmonary hypertension may be triggered by the narrowing of vascular lumen secondary to the circumferential thickening brought about by intimitis in the non-embolized small artery, but not by thromboembolic pulmonary arteritis.

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Twenty-two patients with pulmonary aspergilloma were discussed concerning the immunological reaction. Skin reaction using Aspergillus fumigatus antigen was generally immediate and mono-phasic. A high IgE level and Aspergillus fumigatus-specific IgE antibody were recognized in 30% of the patients. Especially in one patient there was more than a 12, 000IU/ml level of serum IgE and an IgE RAST score 3 of Aspergillus fumigatus specific IgE antibody. Precipitin antibody and lymphocyte stimulation tests using Aspergillus fumigatus antigen were positive in 70% and 50% of the patients, respectively. Of these patients, a case with pulmonary aspergilloma indicated the same immunological reaction as a patient with ABPA. Tuberculin reaction showed a negative or pseudo-positive reaction in 62% of the patients.
Immunological reaction to pulmonary aspergilloma was thought to be useful for diagnosis, analysis of pathogenesis and in determining the necessity for treatment of the disease in question.

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Recently, it has been reported that leukotrienes (LTs) may mediate hypoxic pulmonary vasoconstriction (HPV). This study was designed to determine whether LTs play a role in mediating HPV.
In five anesthetized thoracotomized mongrel dogs, the left lower lobe (LLL) and the rest of the lung were ventilated independently and synchronously with a dual-piston respirator with 100% O₂. Lobar hypoxia (95% N₂ and 5% CO₂ ventilation) was challenged in the LLL before and after administration of AA-861 (5-lipoxygenase inhibitor). HPV did not change before or after administration of AA-861.
Moreover, in other five dogs, SRS-A (slow reacting substance of anaphylaxis) in the serum from LLL vein and LLL extracts were measured by guinea pig ileum bioassay before and after LLL hypoxic challenges. However typical responses of the guinea pig were not observed. We conclude that LTs do not play a role in mediating HPV in dogs.

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We investigated the influence of cigarette smoking on lung function in 448 healthy adult males.
1) Cigarettes per day influenced the FEV_1.0/predicted percent ratio most significantly, and the influence of cigarette smoking contained three components of cigarettes per day, smoking years and their interaction was more significant in Tiffeneau's FEV_1.0/VC ratio, V₂₅, V₂₅/HT.
2) We found no relationship between the influence of cigarette smoking and Gaensler's FEV_1.0/FVC percent ratio. So Tiffeneau's FEV_1.0/VC percent ratio should be used for the evaluation of the influence of cigarette smoking.
3) To adjust for the influence of age and height, we used a percent ratio for predicted value. However results were not adjusted for their influence.

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Serum squamous cell carcinoma-related antigen (SCC-Ag) levels in 95 newly diagosed untreated patients with primary lung cancer and 20 metastatic pulmonary tumors were compared with those in 108 adult controls and 227 nonmalignant pulmonary disease's patients. Serum SCC-Ag was raised (<2.4ng/ml) in 45.2% of primary lung cancer patients (mean 3.51±4.24ng/ml, accuracy 65.9%). The serum SCC-Ag level was elevated in 27/40 (67.5%) of squamous cell type cancer which was higher than other types (accuracy 74.5%).
The mean serum level of SCC-Ag in healthy volunteers was 1.4ng/ml with 6.5% positivity, and 2.01±0.97ng/ml (the positive rate was 24.3%) in patients with non-malignant diseases. A significant difference was obtained between primary lung cancer patients serum SCC-Ag level, and those with non-malignant pulmonary diseases and adult control group respectively (p<0.001). Serial measurement in 40 squamous cell type tumor patients receiving chemotherapy or surgical resection showed an excellent correlation between serum SCC-Ag and clinical response, and a quick elevation was obtained during recurrence. A good combination assay correlation was obtained between serum SCC-Ag and CEA or TPA in primary lung squamous cell carcinoma.
These studies indicate that serum SCC-Ag may be a useful marker for detecting, staging and for monitoring response to therapy in patients with squamous cell carcinoma of the lung.

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Morphologic details of naphthalene-induced bronchiolar lesions with an emphasis on the consequences of Clara cell degeneration, necrosis and regeneration were described. We examined these changes using light microscopy, scanning electron microscopy and transmission electron microscopy. Single dose of intraperitoneal administration of naphthalene resulted in extensive degeneration and necrosis of Clara cells. Subsequently there was necrosis and detachment of ciliated cells from the bronchiolar basal lummina. The remaining Clara cells divided and differentiated into ciliated cell and Clara cell. Injection of naphthalene with pretreatment of piperonyl butoxide did not cause any changes in bronchiolar epithelial cells. The results indicated that naphthalene was metabolized by a cytochrome P-450 dependent mixed-function oxidase system. Cytochrome P-450 was probably present in smooth endoplasmic reticulum, rough endoplasmic reticulum and the perinuclear space of Clara cells.

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We investigated intrathoracic lesions in 191 adult leukemia patients hospitalized and autopsied in our hospitals in the past 30 years. Autopsy protocols, records of clinical course and chest roentgenographic findings were examined. Intrathoracic lesions were found in 178 of 191 patients (93.2%). Major intrathoracic lesions in leukemia patients included pulmonary hemorrhage in 32.5% of the cases, pulmonary edema in 30.4%, pulmonary congestion in 28.3%, leukemic lung infiltration in 27.8%, bronchopneumonia in 25.1%, pleural effusion in 15.7%, aspergillosis in 13.1%, pulmonary infarction in 6.3%, pulmonary abscess in 6.3%, atelectasis in 6.3%, petechia of the pleura in 5.2% and leukemic infiltration of pleura in 4.7% of the cases.
Minor intrathoracic lesions included mucormycosis in 4.2% of the cases, candidiasis in 4.2%, pneumocystis carinii pneumonia in 3.7%, pulmonary thrombosis in 3.7%, interstitial pneumonia in 2.1%, hemothorax in 1.6%, hilar lymph node swelling in 1.6%, hyaline membrane formation in 1.6%, cytomegalovirus infection in 1.1% and miliary tuberculosis in 1.1% of the cases.
Usually many leukemia patients had more than two intrathoracic lesions.

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A 46 year-old woman was admitted because of dyspnea. A chest roentgenogram showed diffuse reticulo-nodular shadows and small cystic change in the lung field, and which showed rapid progression. TBLB for the purpose of diagnosis could not performed but we diagnosed this case clinically as diffuse pulmonary hamartoangiomyomatosis. We had treated her for respiratory failure with administration of oxygen for about 3 years after admission. Though she had inhaled relatively high concentration of oxygen and analysis of blood gas showed over 75 Torr of hypercapnia during 18 months, she could maintain her daily life style due to a process of sufficient compensation.
It has been recognized that overinflation of lung had been the characteristic of diffuse pulmonary hamartoangiomyomatosis in chest roentgenogram, but this case mainly showed reticulo-nodular shadow with small cysts. It was suggested by autopsy that small cysts and a reticulo-nodular shadow reflected the proliferation of smooth muscle fiber.
There was no particularly stenosis of large airways in this case. So it was suggested that obstructive findings of this disease had resulted from abnormal proliferation of smooth muscle in the area of respiratory bronchiole and terminal bronchiole. It was thought that stenosis of this area caused air-trapping and multiple cystic change.

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A 17 year-old girl was admitted to our clinic, complaining of progressive dyspnea and dry cough for 4 months.
The chest X-ray plan showed no abnormality except for over-inflation. The pulmonary function test revealed a severe obstructive pattern. Prednisolone and medroxyprogesterone were given for probable bronchiolitis and pulmonary hamartoangiomyomatosis, but were not effective.
Three months later, she committed suicide, because of progressive dyspnea. Concerning the autopsy findings, the lung cut-surface showed an almost normal appearance, although mild thickening of the wall and mild stenosis of the lumen were partially noticed from the small bronchi to the non-respiratory bronchioles.
Histologically, the granulation tissue was present in the tunica propria of the same area. However, there was no remarkable change in the respiratory bronchioles and alveoli. These findings seem to be compatible with “bronchobronchiolitis obliterans” (Yamanaka), except for marked foamy cell aggregation in the wall of small bronchi and non-respiratory bronchioles.

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We recently experienced one case of pulmonary dirofilariasis, a 39 year-old male who had kept a dog in his childhood. He had a coin lesion of homogeneous density in the left lingual segment and had no symptoms.
Partial resection of left S₄ was done, and the pathologic finding showed the body of male dirofilaria immitis surrounding granular tissue.
The total number of cases of this disease found in the literature in Japan was 21 and they were discussed in detail.

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A 79 year-old male was admitted to our hospital with productive cough, sputum and dyspnea. On physical examination, bubbling rales and wheezing were heard at the lower field of both lungs. Chronic nasal sinusitis was identified. Chest X-ray films revealed disseminated small nodular shadows and tram lines in both lower lung fields. His clinical picture and chest X-ray findings demonstrated diffuse panbronchiolitis. In spite of the administration of antibiotics and steroid hormones, he died of respiratory failure.
The macroscopic view of the cut surface of the autopsied lungs showed many small yellowish nodules in the parenchymal area and ectatic changes in the peripheral airways. On histologic examination, small nodules were found in the area of the respiratory bronchioles. The walls of this compartment were thickened by the infiltration of mononuclear cells extending to the peribronchiolar alveolar areas. Granulation tissues had formed in the lumens of the respiratory bronchioles, and foamy cells had been accumulated in the peribronchiolar areas. These are typical pathologic features of diffuse panbronchiolitis.
In addition to the pathological findings of diffuse panbronchiolitis, the case was associated with disseminated candidiasis, producing numerous microabscesses in the following organs: lung, liver, kidney, pancreas, heart and brain. Antibiotic therapy with steroid hormones for a longer period might have played an important role in the pathogenesis of disseminated candidiasis.

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