We studied whether endothelin-1 (ET-1) and leukotoxin (Lx), which have a different effects on vascular tone in isolated perfused rat lungs, also have different effects on mitochondrial function in edematous lung injury. Lung mitochondria were extracted from isolated perfused rat lungs exposed to each mediator. In lungs exposed to 0.5nmol of ET-1, lung wet weight increased with a markedly elevated perfusion pressure but with no increase in the release of lactate dehydrogenase (LDH), an index of cell damage, into the perfusate. Neither mitochondrial respiration rate nor ATP content in the lung tissue differed from those of untreated lungs. In contrast, in lungs treated with 30μmol of Lx, lung wet weight markedly increased despite a small elevation of perfusion pressure; release of LDH into the perfusate increased, and the mitochondrial respiration rate in state 3 and 4 significantly decreased while the ATP content in the lung tissue was less than in untreated lungs. We also examined cellular and mitochondrial damage in hydrostatic lung edema caused by raising an outflow reservoir. Mitochondrial respiration was not suppressed, and perfusate LDH activity was not increased, although lung wet weight increased as much as it did after the treatment described above. These results indicate that lung mitochondrial function is differentially affected by ET-1 and Lx, and they suggest that abnormalities in energy production by lung mitochondria are related to permeability edema.

View full abstract

Type-1 hereditary motor and sensory neuropathy (HMSN I) is a slowly progressive disease resulting in distal muscle weakness with atrophy, and in sensory disturbance. Restrictive lung disease and respiratory muscle failure, common in many advanced neuromuscular disorders, is not a predominant feature of HMSN I. Recently, there have been sevreal reports of respiratory dysfunction in patients with HMSN I, complicated by diaphragmatic weakness. In five patients with HMSN I (3 men and 2 women, mean age 55.4 yrs), we measured spirometric variables, maximal inspiratory pressure, and maximal expiratory pressure, in both sitting and supine positions. We also studied phrenic nerve conduction by cutaneous stimulation at the posterior border of the sternocleidomastoid muscle. Four of five patients had low maximal inspiratory pressure and abnormally long phrenic nerve latency. Two patients showed evidence of a restrictive lung disorder and daytime alveolar hypoventilation. All-night polysomnography in those two patients revealed periodic decreases in arterial blood oxygen saturation, and episodes of central apnea.
We conclude that diaphragmatic dysfunction is not rare in HMSN I, and that maximal inspiratory pressure and phrenic nerve conduction may be useful in the early detection of phrenic nerve involvement.

View full abstract

To assess whether diffusion-limited gas exchange plays a significant role in hypoxemia in various types of chronic obstructive pulmonary disease (COPD), we analyzed the distribution of ventilation-perfusion (V_A/Q) ratios and of diffusing capacity-perfusion (G/Q) ratios. We compared V_A/Q and G/Q distributions in patients with three basic types of COPD: emphysematous changes, bronchiolar involvement, and airway hypersecretion, which were classified based on symptoms and on findings of high-resolution CT. The results were that 1) hypoxemia was not caused by diffusion-limited gas exchange with low G/Q regions in any type of COPD, that 2) hypoxemia in COPD was caused by inhomogeneities in V_A/Q distribution, that 3) emphysematous changes and bronchiolar involvement were associated with high and low V_A/Q regions, respectively, and that 4) either hypersecretion itself or related airway abnormalities may cause low V_A/Q regions to form.

View full abstract

To study the contribution of polymorphonuclear (PMN) and mononuclear (MN) phagocytes to the development of acute lung injury, we studied lunginjury after intratracheal instillation of lipopolysaccharide (0.02mg/kg) in guinea pigs previously exposed to heat-killed Corynebacterium parvum. In one group, cyclophosphamide was given to deplete peripheral PMNs. In another group, gadolinium chloride (GdCl₃) was injected to suppress the function of MNs. Four hours after instillation of lippoly soccharide, the animals were killed, bronchoalveolar lavage was done, and the lungs were examined histopathologically. ¹²⁵I-labeled albumin was injected to estimate the endothelial damage, and ¹³¹I-labeled albumin was injected to correct for blood contaminsation in the samples. In the group given cyclophosphamide, lung injury was no less than in the control group. In contrast, lung injury was less severe in the group given GdCl₃ than in the control group. These findigns suggest that MN are important in the pathogenesis of lung injury, especially in individuals who are immunologically primed by infection.

View full abstract

Seventy-two patients with chronic obstructive pulmonary disease (COPD) underwent right heart catheterization when they were clinically stable and the relationship between length of survival and acute pulmonary vascular response to 100% oxygen inhalation was studied. Oxygen inhalation significantly reduced mean pulmonary arterial pressure (PPA), cardiac index (CI), and pulmonary arteriolar resistance (PAR). The percent change in PAR (%ΔPAR) was used as an index of the acute pulmonary vascular response to 100% oxygen inhalation. Each patient was classified as a responder (%ΔPAR≥15%) or a nonresponder (%ΔPAR<15%). The cumulative survival rates of these two groups were compared. Responders survived significantly longer than did nonresponders (mean survival times were 2571 days and 1432 days, respectively). The two groups did not differ significantly in anthropometic data, pulmonary hemodynamics, or blood gas data measured at base line during air inhalation. Howevere, FEV₁ and VC were significantly lower in nonresponders than in responders. The %ΔPAR was not significantly related to age, PPA, PAR on air inhalation, FEV₁, FEV₁%, VC, or %VC. We conclude that the pulmonary vascular response to oxygen inhalation (%ΔPAR) may be an independent prognostic factor in patients with COPD.

View full abstract

We examined patterns of growth of cancer cells in specimens of alveoli taken from 41 patients with squamous cell carcinoma (36 men and 5 women, mean age of 65 years). For comparison, 8 samples from patients with small cell carcinoma (6 men and 2 women, mean age 64) and 71 samples from patients with adenocarcinoma (48 men and 23 women, mean age 62) were also studied. The samples were fixed in formalin, embedded in paraffin, and then subjected to immunostaining. Gladular structures composed of non-atypical cuboidal cells with negative p53 staining and scanty positive PCNA staining were found in 90% of the samples of squamous cell carcinoma.
In small cell carcinoma, 25% of the samples had small numbers of non-atypical glandular structures. In adenocarcinoma, no non-atypical glandular structures were seen. Glandular structures were observed in the periphery of the cancerous tissue. Some of these non-atypical cells were attached to the alveolar basement membranes. We conclude that squamous cell carcinoma grows between the basement membrane and the alveolar epithelium, and leaves noncancerous epithelium with glandular structure.

View full abstract

Regular measurement of peak expiratory flow rate (PEF) has been recommended as an aid in the management of asthma, but the time of the day when PEF should be measured remains unclear. We therfore sought to determine the optimal time for measuring PEF in untreated patients with mild to moderate asthma. PEF was measured in 11 patients four times daily: on waking, around noon, in the evening, and at bedtime. Significant (p<0.05) rhythms were detected by single cosinor analysis in all patients. Analysis by the population mean cosinor method showed that the mesor was 381±120l/m, the amplitude was 52±21l/m, and the acrophase was at 16:28±0:55. These data indicate that, in general, PEF is lowest at 4:30 a. m. and highest at 4:30 p. m. in patients with mild to moderate asthma. We conclude that PEF should be measuremed early in the morning and at 4:30 p. m. in such patients.

View full abstract

A 68-year-old man had chronic pleural empyema, an alveolar fistula, and purulent perichondritis. The pericostal abscess extended beneath both sides of the costal arch and had a cutaneous sinus in the right hypochondrium, but it did not communicate with the cavity of the pleural empyema. In separated operations, the entire costal arch was resected and the alveolar fistula was closed with the pedunculate latissimus dorsal muscle. Neither tuberculosis bacilli nor tubercular granulomas were seen in resected specimens, The postoperative course was uneventful and the pericostal abscess healed, but the alveolar fistula recurred and the patient died of pneumonia 3 years and 6 months after the first surgery.

View full abstract

Mediastinal parathyroid cysts are very rare. Since the first report by DeQuervain, 19 cases have been reported. We encountered a case of mediastinal parathyroid cyst presenting as displacement of the trachea. The cyst originated in the lower portion of the left lobe of the thyroid gland and extended to the mediastinum, displacing the trachea and the esophagus. The monolocular mass was a thin walled cyst, and mognetic resonance imaging indicated that it contained watery fluid. The left lobe of the thyroid gland was found to be displaced upward by the tumor, on thyroid scintigram done with technetium 99, which suggested that the cyst originated in the parathyroid gland.

View full abstract

A 24-year-old woman was admitted to our hospital due to moderate asthmatic attacks. Dyspnea and hypoxemia progressed gradually despite medication. A chest roentgenogram revealed left unilaterly hyperlucency with pneumomediastimmn and subcutaneous emphysema. Swyer-James syndrome was diagnosed. Several cases of Swyer-James syndrome with bronchial asthma airway hyperresponsiveness have been reported, but we know of no reports of Swyer-James syndrome with pneumomediastinum and subcutaneous emphysema due to prolonged asthmatic attacks. Pneumomediastinum and subcutaneous emphysema may be caused by abnormally high pressures in the bronchial lumen and alveolar space during asthmatic attacks, because the emphysematous lesion may be structurally weak.

View full abstract

We describe two cases of pneumonia caused by Sho-saiko-to. Patient 1 was a 61-year-old man with type-C liver cirrhosis. About 50 days after starting to take Sho-saiko-to, he complained of fever and diarrhea, and progressive dyspnea developed. Analysis of arterial blood obtained in the emergency room showed severe hypoxemia:, PaO₂ 26Torr. A chest radiograph and a CT scan showed bilateral diffuse fine granular and ground-glass opacities predominantly in the upper lung fields. Despite repeated pulse therapy with methylprednisolone and aggressive medical treatment including mechanical ventilation, the patient remained in respiratory distress, which was later complicated by gsstrointestinal bleeding. He died on the 45th hospital day. The bronchoalveolar lavage contained abnormally high fluid percents of lymphocytes and neutrophils. Postmortem examination of the lungs revealed alveolar septal thickening, marked hyperplasia of type 2 pneumocytes, and no hyaline membrane formation.
Patient 2 was a 68-year-old man. Eighty days after he began taking Sho-saiko-to, he presented with a 4-day history of shortness of breath accompanied by fever and progressive coughing. On arrival of the hospital, arterial blood gas analysis showed mild hypoxemia (PaO₂, 61Torr) and a chest radiograph revealed bilateral irregular infiltrates in the lower lung fields. Analysis of bronchodveolar lavage fluid showed an abnormally high percent of lymphocytes (especially CD8 + lymphocytes), and examination of a biopsy specimen revealed exudates of fibrin and neutrophils in the alveolar spaces and patechy intraluminal organization. The response to prednisolone was good and he was discharged on the 40th hospital day in stable condition. Drug lymphocyte stimulation tests of peripheral blood to Sho-saiko-to were positive in both patients.
Patient 2 was though to have a typical case of Sho-saiko-to-induced pneumonia, and patient 1 was thought to have fulminating variant of this disease.

View full abstract

We encountered a case of chronic pulmonary paracoccidiodomycosis in Japan. A 53-year-old Japanese man, who had worked in Brazil from 1964 to 1969. Came to our hospital because of abnormal shadows on a screening chest roentgenogram. In 1989, he had been treated with fluconazole for mucocutaneous-lymphangitic paracoccidioidomycosis with oral ulceration and neak hymphadenitis. Chest roentgenograms and computed tomograms showed diffuse small nodular and emphysematous shadows. Microscopical examination of specimens obtained by transbronchial lung biopsy showed no abnormality. He was treated with oral fluconazole, and the abnormal radiographic shadows regressed. We believe that this was the first case of chronic pulmonary paracoccidioidomycosis in Japan.

View full abstract

A 75-year-old man who worked at a horse racing track, had an abnormal shadow on a chest radiography. He had a history of dilated cardiomyopathy and mitral regurgitation but had not had any respiratory or systemic symptoms for two years.
Chest radiographs and CT scans showed slowly increasing consolidation with internal areas of low attenuation, and without cavity formation, at the left S⁸. The erythrocyte sedimentation rate, C-reactive protein level, WBC count, percentage of eosinophils, and IgE level were 35mm/hr, negative, 8400, 17%, and 3628IU/ml, respectively. Eosinophils were found in samples of sputum. His immunological status was normal.
Transbronchial lung biopsy yielded necrotic tissue, along with gram-positive and irregular acid-fast branching filaments that grew in culture. The microorgansim was identified as Nocardia asteroides.
Occupational inhalation of soil may have caused his disesase.

View full abstract

A 52-year-old man with an 8-year history of rheumatoid arthritis was admitted to the hospital because of coughing and purulent sputum. A chest X-ray film obtained on admission showed small nodular shadows without overinflation in both lower lung fields, and a high-resolution CT scan showed many micronodular shadows in the centrilobular regions. Follicular bronchiolitis was diagnosed from the results of an open-lung biopsy, and prednisolone therapy was started at a dosage of 40mg/day. Sinusitis developed 4 years later. Five years after the start of steroid therapy, dilation of bronchi and thickneing of bronchial walls appeared on a CT scan, which also showed areas of low attenuation that were presumed to be bronchiolitis obliterans. These findings suggest that the pattern of airway disease can vary during the course of rheumatoid arthritis.

View full abstract

A 62-year-old man was admitted to our hospital with complaints of coughing and fever. He had had poliomyelitis at the age of 4 years, and had experienced difficulty in swallowing and chronic aspiration for the past 3 years. A chest roentgenogram and a high-resolution CT scan obtained on admission showed many small nodular shadows in the lower lung fields. Cricopharyngeal myotomy was done to decrease aspiration. The patient was then able to eat without aspiration, and the chest-roentgenographic and CT findings improved. Diffuse aspiration bronchiolitis was diagnosed from the clinical course and the radiographic findings. Cricopharyngeal myotomy can reduce the risk of aspiration in patients with diffuse aspiration bronchiolitis.

View full abstract

A 65-year-old woman was admitted to our hospital because of severe anemia. A skin biopsy was done in January 1994 and sarcoidosis was diagnosed. Diffuse reticular shadows were seen in both lung fields on a chest X-ray film and mediastinal lymph node swelling was seen on a chest CT scan. She was followed as an outpatient and was not treated. She suddenly experienced vertigo and general fatigue in March 1995. Laboratory findings on admission were as follows: Hb 6.2g/dl, MCV 115.9fl, Ret 198%, LDH 732IU/L, I-Bil 1.9mg/dl, and Coombs' test was positive. Autoimmune hemolytic anemia was diagnosed, and she was treated with prednisolone (1mg/kg). As of the time of this writing, she has no relapse of hemolytic anemia even though prednisolone was discontinued 6 months ago.

View full abstract

A 73-year-old woman with diabetes mellitus and hypothyroidism had been well until 4 days before she presented with fever, productive coughing, and general malaise. Dyspnea gradually worsened, and she was admitted to Kobe City General Hospital. She appeared toxic and was in moderate respiratory distress on admission. There were scattered rales in both lung fields.The abdomen was soft with no tendernes. A chest roentgenogram showed peripheral infiltrates in both lung fields. Arterial blood gas analysis showed a P_O2 of 48.6Torr and a P_CO2 of 27.2Torr. A blood culture on admission showed Escherichia coli. Computerized tomography of the chest showed multiple nodules of various sizes in the peripheral lung fields. Some nodules had necrotic centers and feeding vessels. Wedge-shaped lesions abutting the pleura were also seen. These findings strongly suggested septic pulmonary emboli.
An abscess in the left kidney, which was considered to be the source of the septic pulmonary emboli, was found with Ga scintigraphy, ultrasonography, and computerized tomography of the abdomen. Treatment with antibacterial drugs was effective against the lung lesions but not the renal abscess. A left nephrectomy was done. In the proper clinical setting, characteristic CT features of septic emboli can contribute to early diagnosis of this disease.

View full abstract

A 26-year-old man was admitted to the hospital with chest radiographic findings of an infiltration shadow in the right upper lung field and no hilar lymphadenopathy. A high-resolution CT scan of the chest showed small nodular shadows which corresponded to agglomerations of granulomas. Histological examination of a specimen obtained by transbronchial biopsy revealed a sarcoid-type granuloma in the bronchial submucosa. Pulmonary sarcoidosis without radiographic evidence of hilar lymphadenopathy is rare.

View full abstract