田邉 信宏

BACKGROUND: The pathogenesis of daytime hypercapnia (Paco2 >or= 45 mm Hg) may be directly linked to the existence of obstructive sleep apnea syndrome (OSAS) per se, although only some patients with OSAS exhibit daytime hypercapnia. OBJECTIVE: To investigate the prevalence of daytime hypercapnia in patients with OSAS; the association of daytime hypercapnia and obesity, obstructive airflow limitation, restrictive lung impairment, and severity of sleep apnea; and the response to continuous positive airway pressure (CPAP) therapy in a subset of subjects. METHODS: The study involved 1,227 patients with OSAS who visited a sleep clinic and were examined using polysomnography. As for the response to CPAP therapy, the patients were considered good responders if their daytime Paco2 decreased >or= 5 mm Hg and poor responders if it decreased < 5 mm Hg. RESULTS: Fourteen percent (168 of 1,227 patients) exhibited daytime hypercapnia. These patients had significantly higher body mass index (BMI) and apnea-hypopnea index (AHI) values compared with normocapnic patients, while percentage of predicted vital capacity (%VC) and FEV(1)/FVC ratio did not differ between the two groups. Logistic regression analysis showed that only AHI was a predictor of daytime hypercapnia (p < 0.0001), while BMI (p = 0.051) and %VC (p = 0.062) were borderline predictors of daytime hypercapnia. Daytime hypercapnia was corrected in some patients (51%, 19 of 37 patients) with severe OSAS after 3 months of CPAP therapy. CONCLUSION: The pathogenesis of daytime hypercapnia may be directly linked to sleep apnea in a subgroup of patients with OSAS.

BACKGROUND: The purpose of this study was to evaluate the usefulness and safety of multidetector-row computed tomography (MDCT) pulmonary angiography and indirect venography management of acute pulmonary embolism (PE), including indication for inferior vena cava (IVC) filter. METHODS AND RESULTS: Seventy-one consecutive patients who were clinically suspected of PE and underwent 16-slice MDCT pulmonary angiography and indirect venography were enrolled. Management included indication of IVC filter for patients with extensive deep venous thrombosis (DVT) in submassive or massive PE. A right ventricular to left ventricular short-axis diameter by MDCT>1.0 was judged as submassive PE. All patients were followed for 1 year. MDCT identified 50 patients with venous thromboembolism and 47 patients had acute PE: 4 were judged as massive, 14 as submassive, and 29 as non-massive by MDCT; 3 patients had DVT alone and 7 patients had caval or iliac DVT. Only 1 patient with massive PE and DVT near the right atrium died of recurrence. No other patients died of PE. CONCLUSION: Management based on MDCT pulmonary angiography combined with indirect venography is considered to be safe and reliable in patients with suspected acute PE.

A 60-year-old man was admitted to our hospital complaining of back pain and bloody sputum. Chest CT scan showed characteristic multiple small nodules with central dense opacity and surrounding faint opacity, suggesting lesions with hemorrhage. Bone scintigram and MRI revealed multiple osteolytic lesions in pelvis and lumbar spine. Biopsy of the bone lesion established a diagnosis of angiosarcoma. Chemotherapy with paclitaxel and palliative radiotherapy for the bone were initiated. Pulmonary metastases dramatically diminished after 4 courses of paclitaxel treatment. After eight weeks, the tumor recurred. Salvage chemotherapy of weekly administration of docetaxel yielded limited effects. The patient died of cancer one year after treatment initiation.

A 30-year-old woman was admitted because of persistent and severe hemoptysis in November 2005. She had been given a diagnosis of interstitial pneumonia (IP) and pulmonary aspergilloma in 2001, and she was treated with oral prednisolone and itraconazole. However she had persistent and intractable hemoptysis. Multi-detector row computed tomography (MDCT) revealed that hemoptysis from the right upper lobe did not originate in bronchial arteries, but the abnormal branches of the right subclavian artery. Surgery was not performed because of her pulmonary function, but she was successfully treated by non-bronchial arterial coil embolization. At 10 months after the embolization, hemoptysis has not recurred. MDCT was very useful for diagnosing the cause of hemoptysis and selective nonbronchial arterial coil embolization might be helpful in treating intractable or refractory hemoptysis.

BACKGROUND: Lipoprotein lipase (LPL) might play a major role in lipid metabolism by hydrolyzing triglyceride-rich lipoproteins. Decreased LPL activity can trigger early inflammatory responses central to atherosclerosis. However, whether repeated apnea-related hypoxemia influences lipid metabolism in patients with obstructive sleep apnea syndrome (OSAS) remain undefined. This investigation determined whether circulating LPL was influenced by repeated apnea-related hypoxemia, and the effect of nasal continuous positive airway pressure (CPAP) therapy on LPL concentrations in OSAS patients. METHODS AND RESULTS: The participants of the study were 155 men with OSAS and 39 men without OSAS. Circulating LPL concentrations decreased with the severity of OSAS. They correlated negatively with serum triglyceride, and the linear regression lines between LPL concentrations and triglyceride in OSAS patients were shifted downward compared with those in non-OSAS patients, suggesting that any pathophysiological factor might decrease LPL activity in OSAS patients. Some OSAS patients were subjected to CPAP therapy for 3 months. CPAP therapy increased LPL concentrations and decreased C-reactive protein (CRP) concentrations. CONCLUSIONS: The present study suggests that repeated apnea-related hypoxemia might affect lipid metabolism and augment inflammatory responses, and CPAP therapy could be effective to decrease inflammatory responses and ameliorate lipid metabolism in patients with OSAS.

This study was designed to determine the effects of the treatment schedule on the interaction between cisplatin and radiation. Cells of a human squamous cell lung cancer cell line were treated with cisplatin and radiation using three treatment protocols: 1-h exposure to cisplatin immediately followed by irradiation (A), 4-day continuous exposure to cisplatin immediately followed by irradiation (B), and 1-h exposure to cisplatin followed by irradiation after a 4-day interval (C). The interactions were assessed by isobologram, cell cycle distribution and apoptosis. The combination resulted in a additive effect in every protocol. Cell cycle accumulation at G(2)/M phase before irradiation was observed in Protocols B and C, whereas no cell cycle shift in the limited time course was noted in Protocol A. Although a 4-day continuous exposure to cisplatin and a 1-h exposure to cisplatin followed by a 4-day interval before irradiation caused significantly increased apoptosis, an additional increase in apoptosis after irradiation was not observed in Protocols B and C, whereas Protocol A showed an additional increase. Despite a cell cycle shift favoring radiation sensitivity, the drug-radiation interactions in Protocols B and C were additive, possibly because of negative effects including induction of a durable G(2)/M-phase arrest and suppression of apoptosis by cisplatin. (C) 2007 by Radiation Research Society

Background. Obesity, hypertension, dyslipidemia, and hyperglycemia are prevalent in obstructive sleep apnea syndrome (OSAS). Metabolic syndrome, however, is defined by visceral fat obesity plus at least two of these factors. However, whether OSAS contributes to the development of metabolic syndrome has not been defined. We investigated whether the components of metabolic syndrome were associated with OSAS in nonobese patients. Methods: We investigated the occurrence of hypertension, dyslipidemia, and hyperglycemia in 42 men with OSAS and 52 men without OSAS matched for age, body mass index (BMI), and visceral fat accumulation. Results: Although serum levels of triglycerides, high-density lipoprotein cholesterol, and diastolic BP did not differ significantly between the two groups, fasting blood glucose (111 +/- 6 mg/dL vs 93 +/- 3 mg/dL) [mean +/- SE] and the percentage of hypertensive patients(45% vs 15%) were significantly higher in the group with OSAS. In addition, a significantly higher percentage of patients, with OSAS (19% vs 4%) had at least two of the following: hypertension, hyperglycemia, and dyslipidemia. Logistic regression analysis showed that the apnea-hypopnea index value was the predictor of number of metabolic syndrome parameters such as hypertension, hyperglycemia, and dyslipidemia, while BMI and lowest arterial oxygen saturation during sleep did not. Conclusion: Independent of visceral fat obesity, OSAS was associated with hypertension, dyslipidemia, and hyperglycemia. It is possible that OSAS may predispose even nonobese patients to the development of metabolic syndrome.

Spontaneous regression of a pulmonary lesion in patients with Wegener's granulomatosis (WG) is rare, and only a few such reports have been published. We describe a rare case of a patient with WG in which the pulmonary lesion regressed spontaneously. The patient was a 76-year-old man presenting with fever, sputum and cough. On serial CTs, he had a solitary nodule in the right lung that regressed spontaneously while new multiple nodules developed during a 1-month interval. Biopsy of the new lesions by video-assisted thoracostomy (VATS) established a diagnosis of WG. Treatment with glucocorticoid and cyclophosphamide significantly ameliorated his condition. Concordant with similar previous reports, the mechanisms behind spontaneous regression of pulmonary lesions in the present case seemed to include spontaneous improvement of infection or infarction caused by vasculitis, in addition to regression of the WG lesion itself. Although it occurs rarely, physicians should be aware of the phenomenon that pulmonary lesions in WG could progress and regress spontaneously.

There have been no reports on acute pulmonary embolism (APE) after earthquakes. Our aim was to clarify the actual the occurrence of APE following the 2004 Mid Niigata Prefecture earthquake in Japan, and to assess the risk factors for APE after the event. We sent questionnaires to 122 hospitals in the Niigata Prefecture after the earthquake. Cities, towns, and villages in the prefecture were classified into two areas (high evacuee rate area, and low evacuee rate area) due to the mean ratio of evacuees to the overall population during 1 week immediately after the earthquake. A rate of 5% and higher was encountered for the high evacuee rate area and a rate of &lt; 5% was encountered for the low evacuee rate area. Ten out-of-hospital cases of APE (seven in the high evacuee rate area and three in the low evacuee rate area) were diagnosed within the first month after the earthquake. The relative risk of APE was high in the high evacuee rate area (13.09; p = 0.0002) and also higher in women (8.55; p = 0.04). All patients in the high evacuee rate area had stayed in their automobiles for long periods of time, but none had done so in the low evacuee rate area (p = 0.008).

Background Angiotensin-converting enzyme (ACE) plays an important role in vascular remodeling in pulmonary hypertension, and ACE gene polymorphism is associated with exercise-induced pulmonary hypertension in Japanese patients with chronic obstructive pulmonary disease. The present study was designed to investigate if ACE-insertion (I)/deletion (D) polymorphism might be related to the susceptibility, severity, and disease outcome in chronic thromboembolic pulmonary hypertension (CTEPH). Methods and Results ACE-I/D genotypes were determined in 95 consecutive CTEPH patients (46 underwent surgery, 49 received medical treatment) and 97 controls. The frequencies of genotypes and alleles were not significantly different between patients and controls. Clinical characteristics were compared among ACE genotypes (11, ID, DD). ACE D allele carrier (ID plus DD) was associated with a lower 6-min walk test distance compared with D allele non-carrier (II) (330 +/- 102 (mean +/- SD) vs 381 +/- 85 m, p=0.046). Kaplan-Meier analysis in the medically treated group showed significantly deteriorated survival for D allele carriers compared with D allele non-carriers (p=0.0389). Multivariate analysis revealed that age (p=0.013), pulmonary vascular resistance (p=0.008), and D allele carrier status (p=0.021) were independent predictors of survival. Conclusion ACE D allele carrier is possibly one of the prognostic factors for medically treated CTEPH patients.

Background: Although the prophylaxis of acute pulmonary thromboembolism (APTE) in hospitalized patients has been improving in Japan, there is no report concerning APTE of Japanese medical patients. Therefore, the present study was designed to investigate the characteristics of APTE in Japanese patients hospitalized for medical illness, through a retrospective study. Methods: In a total of 1,438 registry patients with pulmonary thromboembolism for recent 10 years, 1,027 patients with APTE were analyzed with respect to underlying diseases or predisposing factors, and clinical course. Results: A hundred thirty three patients hospitalized for medical illness developed APTE, among 433 in-hospital APTE patients. The prevalence of APTE in women was more than in men. The mean age of the patients at diagnosis was 61 ± 17 years. Main risk factors were a prolonged immobilization, stroke, cancer, indwelling central venous catheter. Fifty-four patients had 3 or more risk factors. In-hospital mortality rate was 23%. Conclusions: Japanese patients in this registry had almost the same findings as in western patients, except for some points that had the possibility of demonstrating a difference between westerners and Japanese in the development of APTE. Our results will be available for establishing the prevention of APTE in medical patients in Japan. © Springer Science + Business Media, Inc. 2006.

Background The diagnostic and therapeutic strategy for acute pulmonary thromboembolism (APTE) was published by the Japanese Circulation Society. But in Japan, there has been no report on how to improve the pre-test probability in APTE-suspected cases, to determine a practically available diagnostic strategy, nor has been a report that compares diagnostic methods and therapies for APTE by decision analysis. Methods and Results APTE was found in 66.7% before using diagnostic imaging techniques. Compared with the absence of APTE, prolonged immobilization, cancer, tachycardia, unilateral leg swelling and inverted T-wave in V1-3 were found more often in the presence of APTE. The rate of obtaining the result on the day of ordering the examination test was 100% with arterial blood gas analysis, trans-thoracic echocardiography and computed tomography (CT), 78.2% in D-dimer, 85.5% in pulmonary angiography, and 54.5% in perfusion lung scan. Decision analysis showed that the highest expected utility was anticoagulant over 0.51 in pre-test probability, with CT between 0.13 and 0.51. Conclusions The pre-test probability of APTE has already been high before using specific diagnostic imaging techniques in Japan. Our results showed that the diagnostic strategy for APTE made by the Japanese Circulation Society was available in most hospitals in Japan.

BACKGROUND: Irinotecan, when combined with cisplatin, is an effective treatment for advanced non-small cell lung cancer (NSCLC). This constitutes a rationale for conducting a phase I study of chemoradiotherapy including this combination for locally advanced NSCLC. PATIENTS AND METHODS: Patients with locally advanced NSCLC and a performance status of 0 or 1 were eligible. The protocol consisted of escalating doses of irinotecan on days 1 and 15, and daily low-dose cisplatin (6 mg/m(2) daily for a total dose of 120 mg/m(2)) combined with concurrent hyperfractionated accelerated thoracic irradiation (1.5 Gy twice daily for a total dose of 60 Gy). RESULTS: The maximum tolerable dose was 50 mg/m(2) of irinotecan, and the dose-limiting toxicity was esophagitis. Tumor response was observed in 50% of cases, and the median survival time of the 12 patients enrolled was 10.1 months, including two patients with 5-year disease-free survival. A pharmacokinetics study demonstrated an accumulation of total platinum, but not of free platinum, during the 26-day treatment period. CONCLUSION: The recommended dose for phase II studies was determined.

Malignant tumors induce development of their own stromal tissues during the processes of growth, progression and metastasis. Since the vascular architecture among the various stromal elements is well known to facilitate tumor growth and has been a target of therapy, the importance of stromal fibroblasts has recently been established. To elucidate the interaction between the tumor and its stromal fibroblasts, the present study took advantage of a unique experimental model consisting of a human small-cell lung cancer cell line, WA-ht, and its mouse stromal fibroblast cell line, WA-mFib, both originally derived from a xenograft tumor in a mouse subcutis. Co-culture with the WA-mFib cells significantly augmented the plating efficiency of WA-hT cells in vitro, and their co-inoculation in nude mice shortened latency and tumor doubling time. Histochemical detection of β-gal, transfected into WA-mFib cells, demonstrated their contribution to the nude mouse xenograft tumor formation as its tumor stroma. Elevated hepatocyte growth factor (HGF) from fibroblasts followed by elevated production of vascular endothelial growth factor (VEGF) from both tumor cells and fibroblasts were demonstrated by ELISA in supernatants of their co-culture, accompanied by enhanced colonogenicity of the tumor cells these enhanced features were not observed in their respective monocultures. Antisense oligonucleotides to HGF cancelled these augmentation effects with co-culture. The findings highlight the substantial roles of tumor stromal fibroblasts, interacting with soluble growth factors, in promoting the malignant propensity of the tumor.

Background: There have been many cases of pulmonary thromboembolism (PTE) that were not diagnosed in the acute phase and not classified as chronic thromboembolic pulmonary hypertension (CTEPH). The aim of the present study was clarify the clinical characteristics of chronic PTE. Methods and Results: The study subjects were 601 patients (chronic PTE=92, acute PTE=456, CTEPH=53) who were clinically diagnosed before their death. Dyspnea and chest pain, which are frequently found in acute PTE, were found less frequently in chronic PTE. The diagnosis of chronic PTE is often delayed in cases of mild to moderate severity with atypical onset. Chronic heart failure and chronic respiratory failure were most frequent in chronic PTE, and cerebrovascular disease was present in approximately 15% of the cases of chronic PTE. Pulmonary angiography and ventilation lung scan were used least frequently in acute PTE. Heparin and thrombolysis were used most frequently in acute PTE. Conclusions: Besides the atypical onset and reduced severity, the presence of preexisting diseases may be one of the reasons why the diagnosis for chronic PTE is delayed. The diagnostic and management techniques differ according to the type of PTE.

Objective: To assess the effectiveness and safety of thrombolytic treatment for acute pulmonary thromboembolism (APTE), especially in the hemodynamically stable patients with right ventricular afterload stress. Methods and Results: In a total of 221 patients with APTE, the association between thrombolytic treatment and the clinical outcomes were investigated. Thrombolysis was given to 121 patients (Thrombolytic Group), and the remaining 100 patients were treated with anticoagulation alone (Anticoagulation Group). In both patients with prolonged shock and patients who were hemodynamically stable without right ventricular afterload stress, the rate of death and recurrence of APTE in Anticoagulation Group were similar to those in Thrombolytic Group. In patients with right ventricular afterload stress, better outcomes were observed in Thrombolytic Group than in Anticoagulation Group, although the difference did not reach statistical significance. There was no significant difference in the rate of major bleeding episode between these two groups. Conclusion: Our results suggested that performing thrombolytic treatment in APTE patients with right ventricular afterload stress should be considered even in Japan. © 2004 Elsevier Ireland Ltd. All rights reserved.

Background: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is characterized by repeated oxygen desaturation. Obesity and visceral fat accumulation (VFA) are risk factors for the development of OSAHS. Circulating leptin increases in accordance with body mass index (BMI), and under experimental conditions intermittent hypoxia stimulates leptin production. Methods: The primary objective of this study was to investigate whether hypoxemia during sleep influences the levels of circulating leptin and whether the location of body fat deposits, ie, the distribution of VFA and subcutaneous fat accumulation (SFA), affects circulating leptin levels in patients with OSAHA who are not obese. We assessed VFA and SFA by abdominal CT scan and measured circulating levels of leptin in 96 male patients with OSAHS and 52 male patients without OSAHS matched for BMI. To be matched for BMI in the two groups, patients whose BMIs were &lt; 27 were selected for the OSAHS group. Results: In the whole study group, circulating leptin levels correlated with BMI (r = 0.30), VFA (r = 0.44), SFA (r = 0.28), apnea-hypopnea index (AIII) [r = 0.48], sleep mean arterial oxygen saturation (SaO(2)) [r = 0.59], and sleep lowest SaO(2) (r = 0.37). Multiple regression analysis showed that average SaO(2) (p &lt; 0.01) and lowest SaO(2) (p = 0.03) were explanatory variables for serum leptin values, but AHI (p = 0.054), BMI (p = 0.33), NIFA (p = 0.11), and SFA (p = 0.36) were not. Conclusions: These results suggest that sleep hypoxemia may be the main determinant of circulating leptin levels, although the location of body fat deposits could contribute to the elevated circulating leptin levels in patients with OSAHS who are not obese.

Objective: An alteration of high energy phosphate metabolism in muscles may contribute to exercise intolerance. The objective of this study was to clarify the changes in high energy phosphate metabolites in muscles during exercise in patients with non-hypoxaemic chronic obstructive pulmonary disease (COPD), which influences the impairment of muscle metabolism. Methodology: Calf muscle energy metabolism was studied in eight stable non-hypoxaemic COPD patients and eight control subjects, using 31P-magnetic resonance spectroscopy (MRS). MRS spectra were acquired at rest, during exercise at two levels of intensity, and during recovery. The control subjects exercised under both normoxic and hypoxic conditions. The intensity of exercise was standardized by the maximal isometric voluntary contraction (MVC) of the calf muscle and the cross-sectional area (CSA) of calf muscle. Results: MVC and CSA were lower in COPD patients. No significant differences in intracellular pH, inorganic phosphate/ phosphocreatine ratio or percentage recovery in inorganic phosphate/ phosphocreatine ratio were observed between the two groups in muscles at rest, during exercise or during recovery. Conclusions: Muscle metabolites, during exercise standardized by muscle CSA and MVC, did not differ between non-hypoxaemic COPD patients and control subjects. MVC, CSA or both, are assumed to be closely related to muscle metabolism, as no difference in high energy phosphate metabolites was observed for COPD patients compared to control subjects when the load was standardized for MVC and CSA. This suggests that high energy metabolites are consumed to a similar extent in the same muscle volume in non-hypoxaemic COPD patients and control subjects.

Background: Obesity and visceral fat accumulation (VFA) are risk factors for the development of obstructive sleep apnea-hypopnea syndrome (OSAHS), and a subgroup of OSAHS patients acquire hypoventilation. Circulating leptin, an adipocyte-derived signaling factor, increases in accordance with body mass index (BMI) under experimental conditions, leptin selectively decreases visceral adiposity and it is also a respiratory stimulant. Objective: To investigate whether the location of body fat deposits, ie, the distribution of VFA and subcutaneous fat accumulation (SFA), contributes to hypoventilation and whether circulating levels of leptin are involved in the pathogenesis of hypoventilation, which is often observed in OSAHS. Methods: We assessed VFA and SFA by abdominal CT scan, and measured lung function and circulating levels of leptin in 106 eucapnic and 79 hypercapnic male patients with OSAHS. Results: In the whole study group, circulating leptin levels correlated with BMI (r = 0.56), VFA (r = 0.24), and SFA (r = 0.47), but not with PO2 or sleep mean arterial oxygen saturation (SaO2). BMI, percentage of predicted vital capacity, FEV1/FVC ratio, apnea-hypopnea index, sleep mean SaO 2, VFA, and SFA were not significantly different between two groups. Circulating leptin levels were higher in the hypercapnic group than in the eucapnic group. Logistic regression analysis indicated that serum leptin was the only predictor for the presence of hypercapnia (β = 0.21, p &lt 0.01). Conclusions: These results suggest that the location of body fat deposits may not contribute to the pathogenesis of hypoventilation, and circulating leptin may fail to maintain alveolar ventilation in hypercapnic patients with OSAHS.

The aetiology of chronic thromboembolic pulmonary hypertension (CTEPH) is largely unknown and may be heterogeneous, because there are several ethnic differences in the clinical characteristics of CTEPH. Female predominance and a higher ratio of chronic to acute pulmonary thromboembolism have been reported in Japan as compared with the USA. Because such ethnic differences may be controlled by genetic factors, the current study investigated HLA polymorphisms in Japanese patients with CTEPH. HLA typing by serological and/or DNA typing methods was performed (for HLA-A, B, DPB1, DRB1) in 80 patients and 678 controls, and the association of clinical characteristics with HLA alleles was studied. The frequencies of HLA-B*5201 (40 versus 24%) and DPB1*0202 (19 versus 6%) were significantly higher in the patients. HLA-B*5201 positive patients showed a significant female predominance. Total pulmonary vascular resistance and mixed venous oxygen tension were better in the HLA-B*5201 positive patients. In contrast, cardiac index and gas exchange parameters were worse in the HLA-DPB1*0202 positive patients. In the patients carrying HLA-B*5201 and/or -DPB1*0202, the frequency of deep vein thrombosis was significantly lower than the other patients. These observations suggested that both the susceptibility and clinical characteristics of chronic thromboembolic pulmonary hypertension were controlled in part by the HLA-B and -DPB1 loci. Copyright©ERS Journals Ltd 2005.

Background: There are few reports that examine the current imaging and management techniques according to the severity of acute pulmonary embolism (APE) or that clarify whether the management strategy ameliorated the mortality from APE. Methods and Results: The study group were 456 patients with APE who were clinically diagnosed before their death. The severity at diagnosis, and the imaging and management techniques were analyzed. Mortality from APE was 0.8% in patients without shock nor right ventricular overload, 2.7% in patients with right ventricular overload without shock, 15.6% in patients with shock, and 52.4% in patients with cardiopulmonary arrest (p&lt 0.0001). In the more severe cases, pulmonary angiography and trans-thoracic echocardiography were used more frequently, whereas both ventilation and perfusion lung scans were used less frequently. Computed tomography was used widely, regardless of the severity. Thrombolytic therapy and catheter therapy were used more frequently in the more severe cases, but an inferior vena cava filter was the only management strategy that reduced the mortality from APE. Conclusions: The severity of APE at diagnosis affected the selection of both the diagnostic techniques and the type of management. Implantation of inferior vena cava filters reduced the mortality from APE.

Pulmonary capillary perfusion within a single alveolar wall continually switches among segments, even when large-vessel hemodynamics are constant. The mechanism is unknown. We hypothesize that the continually varying size of plasma gaps between individual red blood cells affects the likelihood of capillary segment closure and the probability of cells changing directions at the next capillary junction. We assumed that an increase in hematocrit would decrease the average distance between red blood cells, thereby decreasing the switching at each capillary junction. To test this idea, we observed 26 individual alveolar capillary networks by using videomicroscopy of excised canine lung lobes that were perfused first at normal hematocrit (31-43%) and then at increased hematocrit (51-62%). The number of switches decreased by 38% during increased hematocrit (P &lt 0.01). These results support the idea that a substantial part of flow switching among pulmonary capillaries is caused by the particulate nature of blood passing through a complex network of tubes with continuously varying hematocrit.

The clinical presentation of respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) and desquamative interstitial pneumonitis (DIP) seems to be nonspecific, although well-defined pathologic features have been described. Therefore, the clinical pictures, laboratory, radiologic and bronchoalveolar lavage fluid (BALF) findings, and prognosis of 5 patients with RB-ILD were compared with those of 7 patients with DIP. Cell differentiation in BALF could be helpful to distinguish RB-ILD and DIP. Eosinophils were observed only in DIP. The proportion of macrophages was greater in RB-ILD, whereas that of neutrophils was greater in DIP. In RB-ILD, high-resolution computed tomography (HRCT) revealed diffuse centrilobular, nodular or patchy, ground-glass opacities and peripherally distributed, irregular linear opacities. In DIP, HRCT revealed diffuse, bilateral panlobular ground-glass opacities. Clinical symptoms, abnormal radiologic and laboratory findings improved in 6 months after quitting smoking in all patients with RB-ILD. On the other hand, all patients with DIP required systemic steroid therapy, and steroid therapy was difficult to withdraw in 2 years. RB-ILD could be distinguished from DIP, which is also recognized to be a smoking-related interstitial lung disease in terms of its good prognosis, although small numbers of patients in this study limit drawing a definite conclusion, and further studies are required to determine the long-term prognosis.

An experimental model, in which exogenous gene expression in the lung is achieved, has been established. A fibroblast cell line was transfected with the lacZ gene and was administered to syngeneic mice by either intravenous or intratracheal injection. Enzyme-linked immunosorbent assay and histochemical detection of β-galactosidase revealed efficient gene delivery to the lung by either route. Kinetic studies demonstrated that the expression peaked immediately after the injection, and this high level was maintained for 7 days by intratracheal and for 14 days by intravenous administration. This system may have potential relevance for certain experimental models requiring specific gene delivery to the lung.

Objective: The onset of sarcoidosis may be triggered by any hereditary and/or environmental factor. Among these factors, psychosocial stress may play a critical role in the onset of sarcoidosis. The aim of the present study was to evaluate the influence of stressful life events on the onset of sarcoidosis. Methodology: The social and/or life events experienced prior to diagnosis in 55 patients with sarcoidosis, were evaluated quantitatively using the Social Readjustment Rating Scale (SRRS), the most authoritative method to quantify the magnitude of the events requiring changes in lifestyle. In addition, personality with respect to stress-reactivity was simultaneously evaluated using the Minnesota Multiphasic Personality Inventory (MMPI) alexithymia scale. Both the degree of stress, evaluated by SRRS, and stress-reactivity, evaluated by MMPI scale, of sarcoidosis patients were compared with those of 92 healthy controls. Results: The magnitude of stressful life events was significantly higher in patients with sarcoidosis compared with healthy controls. In addition, capacity for coping with stress was found to be inferior in sarcoidosis patients compared with that in the control groups. Conclusion: These results indicated that psychosocial stress assessed on the basis of alexithymic characteristics of the self perception of stress may be partly implicated in the development of sarcoidosis.

Cancer chemotherapy for haemodialysis patients has never been established. To elucidate the feasibility of cisplatin-based combination chemotherapy for haemodialysis patients with lung cancer, a dose escalation study was conducted. Five haemodialysis patients with lung cancer were treated with cisplatin and etoposide. A starting dose of 40 mg m-2 of cisplatin on day 1 and 50 mg m-2 of etoposide on days 1, 3 and 5 were administered as the first course for the first patient. Membrane haemodialysis was regularly performed three times a week and soon after the completion of therapy. By monitoring toxicity and pharmacokinetics data, the dose was escalated course by course and patient by patient. Dose escalation was completed for the first two patients resulting in full-dose chemotherapy consisting of 80 mg m-2 of cisplatin on day 1 and 100 mg m-2 of etoposide on days 1, 3 and 5. Multiple courses of the full-dose chemotherapy were administered to the other three patients. Toxicity was manageable and tolerable for all. Pharmacokinetics data were comparable to those from patients with normal renal function, except for potential long-lasting higher levels of free platinum in the renal insufficiency group. In conclusion, this standard-dose combination chemotherapy was feasible even for haemodialysis patients. © 2003 Cancer Research UK.

Background. Placement of a silicon tracheobronchial prosthesis in emergency situations has become an established therapeutic option to relieve airway stenosis due to malignant diseases. However, the alternative use of a metallic stent has never been fully evaluated. Purpose. To elucidate the clinical relevance of placing metallic stents in patients with critical airway stenosis due to malignant diseases. Patients and Methods. Thirteen patients with critical airway stenosis treated by placing metallic stents and meeting some defined conditions were retrospectively reviewed in terms of usefulness and adverse events. The stents were placed by flexible bronchoscopes under topical anesthesia in all cases. Results. Metallic stent placement was easy, quick and successful in every patient, and airway stenosis was quickly relieved after the procedure in all patients. Accordingly, dyspnea as assessed by a scoring system was improved from I day to I month after the placement. Performance status was not improved significantly by the procedure. Adverse events of serious nature were observed in 6 of the 13 patients. Conclusion. Metallic tracheobronchial stents for patients with airway stenosis and critical conditions seemed to have advantages in relieving dyspnea. Considering the adverse events, however, the choice of this option should be restricted to patients with limited expected survival.

Arterial oxygenation during sleep in Sherpa highlanders has been relatively unexplored. This study was designed to investigate arterial oxygen saturation (SaO2) and pulse rate (PR) during sleep in 61 Sherpa (29 men, 32 women) who had lived at 3450-3850 m in Nepal, from adolescence through old age, and to estimate the relative effects of aging on arterial oxygenation during sleep. The mean SaO2 during sleep (mSaO2) was found to decrease with age, and to negatively correlate with the mean PR during sleep. About one-third of subjects (n=19) exhibited a periodical fluctuation of SaO2 during sleep. The subjects who exhibited a periodical fluctuation of SaO2 during sleep were older and their mSaO2 were lower compared with those who did not exhibit a periodical fluctuation of SaO2, and the cycle of periodical fluctuation got longer with advancing years. These findings indicated that sleep desaturation occurs in high altitude residents with advancing years. © 2002 Elsevier Science B.V. All rights reserved.

Ku70 protein, cooperating with Ku80 and DNA-dependent protein kinase (DNA-PK) catalytic subunit (DNA-PKcs), is involved in DNA double-strand break (DNA DSB) repair and V(D)J recombination. Recent studies have revealed increased ionizing radiosensitivity in Ku70-deficient cells. The presented study, using a human squamous cell lung carcinoma cell line, demonstrated that introduction of an antisense Ku70 nucleic acid made the cells more radio- and chemosensitive than the parental cells. Ku70 protein expression was suppressed in the cells with antisense Ku70 construct when compared to the wild-type cells. A relatively small but statistically significant increase in radiosensitivity of the cells was achieved by the introduction of the antisense Ku70. The increased radiosensitivity in vitro was accompanied by an approximately two-fold increase in α and α/β values in a linear-quadratic model. The antisense Ku70 increased the chemosensitivity of the cells to some DNA-damaging agents such as bleomycin and methyl methanesulfonate, but not to cisplatin, mitomycin C, and paclitaxel. This system provides us with partial suppression of Ku70, and will be a useful experimental model for investigating the physiological roles of the DNA DSB repair gene. © 2002 Elsevier Science B.V. All rights reserved.