[Pulmonary nocardiosis in a patient with diffuse panbronchiolitis].

A 53-year-old woman under treatment for diffuse panbronchiolitis, complained of fever and bloody sputum, Chest radiograph showed infiltrative shadows in both lung fields. Nocardia farcinica was cultured from BALF and pulmonary nocardiosis was diagnosed. She was successfully treated with sulfamethoxazole-trimethoprim, LVFX. Improvement was clearly demonstrated on chest radiograph. To the best of our knowledge, this is the first reported case of pulmonary nocardiosis in a patient with diffuse panbronchiolitis.

Effects of risedronate or alfacalcidol on bone mineral density, bone turnover, back pain, and fractures in Japanese men with primary osteoporosis: results of a two-year strict observational study.

Although osteoporosis in men is already a major public health problem, there is still a dearth of data about the effects of risedronate in male osteoporosis, especially in Japanese with primary osteoporosis. Therefore, the objective of our study was to investigate the effects of risedronate on bone mineral density (BMD), bone turnover, back pain, and fractures in these patients prospectively for two years (at baseline, three months, six months, twelve months, and twenty-four months) both longitudinally and compared with those of alfacalcidol. The subjects enrolled for this study were 66 Japanese male patients with untreated primary osteoporosis (mean age 63.52 +/- 8.7 years), who were divided into two groups (44 with risedronate and 22 with alfacalcidol). We measured BMD by dual energy X-ray absorptiometry at three sites-the lumbar spine, femoral neck, and distal radius. Risedronate treatment significantly increased BMD at the lumbar spine and at the femoral neck, reduced bone-specific alkaline phosphatase (BAP) and serum N-terminal telopeptide of type I collagen (NTx), and reduced back pain, both longitudinally and compared with alfacalcidol treatment. We observed a lower rate of incident fracture in risedronate users. However, multiple logistic regression analysis revealed that this trend was not statistically significant, possibly because of the small number of patients enrolled. These potentially beneficial effects of risedronate on bone in male patients with primary osteoporosis suggest the possibility that osteoporosis should be treated with risedronate regardless of gender in order to effectively prevent subsequent osteoporotic fractures.

The first imported case of rabies into Japan in 36 years: a forgotten life-threatening disease.

A domestic case of rabies has not been reported in Japan since 1957. The last case of rabies reported in Japan was an imported case from Nepal in 1970. We recently experienced a new case imported from the Philippines, the first case in Japan in 36 years. Although Japanese people are about to forget the dangers of rabies, this case should serve as a warning to those Japanese who are planning a trip abroad.

Efficacy of risedronate in Japanese male patients with primary osteoporosis.

OBJECTIVE: Although osteoporosis in men previously was relatively neglected, bisphosphonates have been strongly suggested as potent therapeutic agents. However, there are few studies on the effects of risedronate in male osteoporosis, especially in Japanese with primary osteoporosis. The aim of our study was to prospectively evaluate the effects of risedronate on bone mineral density (BMD) and bone turnover in Japanese male patients. METHODS: According to the therapeutic regimen, the subjects were divided into two groups (group A, 22 with risedronate; group B, 10 without risedronate). During a one-year study duration, we measured bone-specific alkaline phosphatase (BAP) and serum N-terminal telopeptide of type I collagen (NTx) every 3 months, and BMD at 7 sites by dual-energy X-ray absorptiometry every 6 months. PATIENTS: The subjects were 32 Japanese male patients with untreated primary osteoporosis. RESULTS: In group A, but not in group B, BMD was significantly increased at the lumbar spine both at 6 months and 12 months, and at the femoral neck at 12 months, compared with baseline. Likewise, in group A, but not in group B, both BAP and NTx were significantly decreased at all time points measured (3 months, 6 months, and 12 months), compared with baseline. CONCLUSION: These results confirmed the beneficial effects of risedronate upon increasing BMD and reducing bone turnover markers in Japanese male patients with primary osteoporosis, comparable to those previously reported in postmenopausal patients with osteoporosis.

Three-month changes in bone turnover markers and bone mineral density response to raloxifene in Japanese postmenopausal women with osteoporosis.

It has been well established that raloxifene (RLX) improves bone turnover, increases bone mineral density (BMD), and reduces the risk of fractures. However, it remains obscure how to monitor the therapeutic effects of RLX, while numerous clinical trials for other antiresorptive agents have suggested that greater short-term reductions of bone turnover markers (BTMs) can predict greater increases in BMD and greater reduction in risk of future fractures. The purpose of this study was to investigate associations between short-term reductions of BTMs and subsequent changes of BMD after 1-year treatment with RLX. Seventy-three Japanese postmenopausal women with untreated osteoporosis were selected for this study. Reductions in BTMs [bone-specific alkaline phosphatase (BAP) or serum N-terminal telopeptide of type I collagen (NTx)] after 3 months did not correlate with increases of BMD at any major sites (lumbar spine, femoral neck, total neck, and distal 1/3 radius) either after 6 months or after 12 months. Our results suggest that short-term reductions or 3-month reductions of BTMs with RLX treatment cannot be used to predict increases of BMD. However, this does not directly mean that short-term reductions or 3-month reductions of BTMs with RLX treatment cannot be used to predict risk reduction of future fractures or the ultimate effects of RLX on bone. Further studies with fracture endpoints in longer observation and larger number of patients are warranted to establish how to monitor the therapeutic effects of RLX or early identification of responders or nonresponders to RLX treatment.

Association between baseline values of bone turnover markers and bone mineral density and their response to raloxifene treatment in Japanese postmenopausal women with osteoporosis.

It has been well established that raloxifene improves bone turnover, increases bone mineral density (BMD), and reduces the risk of fractures. However, it remains obscure which patients are more likely to respond to treatment with raloxifene in patients with postmenopausal osteoporosis. The purpose of this study was to investigate associations between baseline values of BMD and bone turnover markers (BTMs) and changes of those values after 1-year treatment with raloxifene. Sixty-eight Japanese postmenopausal women with untreated osteoporosis were selected for this study, among whom 58 patients (mean age 70.40 +/- 9.2 years) completed this study. Lower baseline values of BMD at the lumbar spine, the femoral neck, and the distal radius were significantly correlated with greater increases of BMD at those corresponding sites after 1-year treatment with raloxifene. On the other hand, higher baseline values of bone-specific alkaline phosphatase (BAP) and serum N-terminal telopeptide of type I collagen (NTx) were significantly correlated with greater reductions of BAP and NTx, respectively, after 1-year treatment with raloxifene. Although longer and larger studies with fracture endpoints are needed, our findings suggest that baseline values of BMD and BTMs can be used to predict subsequent skeletal response to raloxifene therapy in Japanese postmenopausal women with osteoporosis.

Increased bone turnover in patients with hypercholesterolemia.

Osteoporosis has been linked with arteriosclerotic vascular diseases, suggesting that hypercholesterolemia or dyslipidemia may be a common pathogenetic factor underlying these diseases. However, little is known about the relationship between osteoporosis and hypercholesterolemia. The purpose of this study was, therefore, to investigate the effects of hypercholesterolemia upon bone metabolism, by measuring bone turnover markers in hypercholesterolemic patients. This study included 281 Japanese patients with hypercholesterolemia, and 267 control subjects. Serum bone-specific alkaline phosphatase (BAP) of the patients was significantly higher than that of the controls in women. Serum N-terminal telopeptide of type I collagen (NTx) of the patients was significantly higher than that of the controls in both men and women. In addition, both BAP and NTx in men showed a significantly negative correlation with high density lipoprotein cholesterol (HDL-C). On the other hand, in women, both BAP and NTx showed a significantly positive correlation with total cholesterol and low density lipoprotein cholesterol (LDL-C). These results indicate increased bone turnover in hypercholesterolemic or dyslipidemic patients regardless of gender, and suggest the importance of treating hypercholesterolemia or dyslipidemia in order to prevent not only arteriosclerotic complications but also osteoporotic bone loss and subsequent fractures.

Efficacy of combined treatment with raloxifene and alfacalcidol on bone density and biochemical markers of bone turnover in postmenopausal osteoporosis.

Because both raloxifene (RLX) and alfacalcidol (ALF) have been established as therapeutic agents for osteoporosis, it is tempting to speculate that the combination therapy of RLX and ALF might provide benefits over that of either one alone. However, the efficacy of the combination therapy has not been reported yet. The purpose of this study was thus to assess the efficacy of the combination therapy on bone mineral density (BMD) and bone turnover in patients with postmenopausal osteoporosis. Sixty postmenopausal patients (mean age 71.62 +/- 9.9 years) with untreated osteoporosis were selected for this study, and were randomly divided into two groups by therapeutic regimen. Group A consisted of 28 patients treated with RLX plus ALF, while Group B consisted of 32 patients with RLX alone. Among them, 20 in group A and 22 in group B completed this study. Contrary to our expectations, at either 6 months or 12 months after the initiation of treatment, RLX plus ALF did not increase BMD at any of the skeletal sites measured, including lumbar spine, femur, and radius, nor did it reduce bone-specific alkaline phosphatase or N-terminal telopeptide of type I collagen more than RLX alone. Our results do not support the hypothesis that the combination therapy of RLX and ALF exerts more beneficial effects on bone compared than with RLX alone. However, it still remains unclear from this study whether the combination therapy of RLX and ALF is more efficacious in preventing fractures compared with RLX alone. Further studies are needed to clarify these issues.

Phase II study of uracil-tegafur plus cisplatin in patients with previously untreated advanced non-small cell lung cancer.

BACKGROUND AND OBJECTIVE: A multi-institutional phase II trial combining uracil-tegafur (UFT) and cisplatin (CDDP) was conducted in patients with previously untreated advanced non-small cell lung cancer (NSCLC) to evaluate the safety and efficacy of this combined treatment regimen. METHODS: The entry criteria for this study were previously untreated NSCLC, measurable disease, age <80 years, performance status <2, and adequate haematological, hepatic and renal function. Patients were treated with 400 mg/m(2) oral UFT from day 1 to day 14 and 80 mg/m(2) cisplatin on day 15. The treatment course was repeated every 3 weeks. RESULTS: Of the 68 patients enrolled, 64 (27 with stage IIIB and 37 with stage IV disease) were eligible for treatment. Twenty of the 64 patients responded to the chemotherapy (response rate 31.3%; 95% CI 21.2-43.4%). The median survival time was 8.6 months, and the 1-year survival was 41.5%. Haematological toxicity >or=WHO grade 3 was seen in 3 (4.7%) patients. For non-haematological toxicities, anorexia with WHO grade 3 was seen in 8 (12.5%) patients, nausea and vomiting with WHO grade 3 in 4 (6.3%), diarrhoea with WHO grade 4 in 1 (1.6%), and liver dysfunction with WHO grade 4 in 1 (1.6%) patient. CONCLUSIONS: The combination of oral UFT plus cisplatin was found to be a safe and active treatment against advanced NSCLC. The observed low toxicity of this combined regimen may warrant its application to the treatment of elderly patients.

Short-term effects of pitavastatin on biochemical markers of bone turnover in patients with hypercholesterolemia.

OBJECT: No consensus has been reached whether clinical use of statins has beneficial effects on bone health, partly due to lower statin concentrations because of first-pass metabolism by the liver. We thus evaluated the effects of pitavastatin, which does not undergo first-pass metabolism, on bone metabolism. METHODS: According to the therapeutic regimen, the subjects were divided into two groups (group A, 66 with pitavastatin; group B, 35 without pitavastatin). Bone-specific alkaline phosphatase (BAP) and serum N-terminal telopeptide of type I collagen (NTx) as bone turnover markers (BTMs) were compared between the two groups and between at baseline and after 3 months of treatment in each group. Correlations between baseline characteristics and deltaBTMs, and between delta lipid profile and deltaBTMs were investigated using both Pearson's correlation analysis and multivariate analysis. PATIENTS: The subjects were 101 patients with untreated hypercholesterolemia. RESULTS: After 3 months of treatment, BAP in group A did not change significantly compared with either the baseline value or that in group B. However, NTx in group A significantly decreased compared with both the baseline value and that in group B. In addition, deltaNTx was negatively correlated with NTx at baseline, and the significance of this correlation persisted after multiple regression analysis. CONCLUSION: Our findings suggest that pitavastatin may have potentially beneficial effects on bone metabolism primarily by reducing bone resorption rather than by stimulating bone formation. Further studies with more patients and longer duration are warranted to evaluate its effects, if any, on prevention of osteoporosis and subsequent fractures.

Clinical significance of 1-year treatment with raloxifene on bone and lipid metabolism in Japanese postmenopausal women with osteoporosis.

It has been well established that raloxifene (RLX) has beneficial effects on bone primarily in Caucasian women. However, to date, there is a dearth of data for Japanese postmenopausal women. In this study, we prospectively evaluated the effects of RLX on bone and lipid metabolism in fifty Japanese postmenopausal patients with untreated osteoporosis. We measured bone mineral density (BMD) by dual-energy X-ray absorptiometry at 7 sites including the lumbar spine, femoral neck, and distal radius. BMD was significantly increased at the lumbar spine both at 6 months and at 12 months compared with at baseline (p<0.01 for both), although the possibility could not be completely excluded that this increase may be partly explained by an apparent increase induced by degenerative changes in lumbar vertebrae since we had no control subjects to compare and be more certain of the findings in this study. Both bone-specific alkaline phosphatase (BAP) and serum N-terminal telopeptide of type I collagen (NTx) significantly decreased both at 6 months (p<0.01 for both) and at 12 months (p<0.01 for both) compared with at baseline, but not below the lower limit of the reference value. Total cholesterol and low-density lipoprotein cholesterol were significantly improved while triglycerides and high-density lipoprotein cholesterol were unaltered. Although longer and larger studies with fracture endpoints are needed to draw definite conclusions, our findings suggest the favorable effects of RLX on bone and lipid metabolism in Japanese postmenopausal women with osteoporosis as in Caucasian women.

[Two cases of chronic atelectasis that improved through use of nasal continuous positive pressure].

We observed improvements in two cases of chronic atelectasis through use of nasal continuous positive airway pressure (nCPAP). Case 1 suffered from middle lobe syndrome accompanied by chronic atelectasis resistant to medical treatment. Case 2 suffered from respiratory failure caused by chronic atelectasis and airway infection complications thereof following a total pneumonectomy and post-pneumonectomy syndrome. The patient was placed on artificial ventilation, and atelectasis was improved by maintaining PEEP and airflow to the atelectatic region. Following extubation we obtained good pneumatization using nCPAP. nCPAP has been reported as effective not only in cases of sleep apnea, but also for cardiogenic pulmonary edema and post-operative atelectasis; we believe it holds great promise for chronic atelectasis as well.

Short-term effects of atorvastatin on bone turnover in male patients with hypercholesterolemia.

No consensus has been reached on whether the 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, known as statins, have beneficial effects on bone health. The purpose of our study was to evaluate the effects of atorvastatin on bone metabolism by means of measuring bone turnover markers in male patients with hypercholesterolemia both at diagnosis and prospectively after 3 months of treatment. Twenty-two Japanese male patients (mean age 62.36 +/- 10.1 years) with untreated hypercholesterolaemeia were selected for this study. After 3-months treatment of atorvastatin, total cholesterol and low density lipoprotein cholesterol significantly decreased as expected (p<0.001 for both parameters). Bone-specific alkaline phosphatase (BAP) did not change significantly (p = 0.444). However, serum N-terminal telopeptide of type I collagen (NTx) significantly decreased by -19.86 +/- 26.4% (p = 0.020). In addition, delta NTx during the course of this study was negatively correlated with NTx at baseline (r = -0.645, p = 0.0008). Although there was a tendency of positive correlations of delta NTx with delta total cholesterol, delta triglycerides, and delta low density lipoprotein cholesterol, and of negative correlations of delta NTx and delta BAP with delta high density lipoprotein cholesterol, none of them reached statistical significance. Our findings suggest that atorvastatin may have potentially beneficial effects on bone metabolism in patients with hypercholesterolemia mostly by reducing bone resorption rather than by stimulating bone formation. Further studies with more patients and longer duration are warranted to evaluate its effects, if any, on prevention of osteoporosis and subsequent fractures.

[Clinical analysis of cases with multidrug-resistant tuberculosis--inpatients at National Hospitals in Kyushu between 1998 and 2003].

PURPOSE: Clinical analysis of inpatients with multidrug-resistant tuberculosis in Kyushu. OBJECT AND METHOD: Clinical analysis of fifty-six patients with multidrug-resistant tuberculosis, who were admitted between 1998 and 2003, at 12 national hospitals in Kyushu was performed retrospectively. RESULTS: The average age was 62.1 +/- 18.6 years, with an age range of 21 to 95 years. There were 44 males and 12 females. Seven of the 14 patients, who were under 49 years old, had not received treatment previously. Twenty nine patients had underlying diseases, which included 10 (17.9%) diabetes mellitus, 5 (8.9%) hepatic disease, and 4 (7.1%) renal insufficiency. Clinical classification of the cases were 54 pulmonary and 2 extrapulmonary tuberculosis. There were 41 (75.9%) bilateral lesions of the lung. In 8 cases, strains were resistant to only 2 drugs (isoniazid, rifampicin). In 27 cases, strains were resistant to at least 5 drugs. The prognosis was as follows: In 27 patients who were resistant to at least 5 drugs, six patients (22.2%) converted to negative on culture and 10 patients (37.0%) died. In 29 patients who were resistant to less than 5 drugs, seventeen patients (58.6%) converted to negative on culture and 6 patients (20.7%) died. Surgical operation was performed in only 7 cases. The sputum smear and culture of 2 surgical patients, who had poor control of diabetes mellitus, became positive thereafter. The other 5 surgical patients were in remission with negative cultures. CONSIDERATION: Half of the patients who were under 49 years old had not received treatment previously. More than half of the patients had underlying diseases. Patients, who were resistant to at least 5 drugs showed a lower bacteriological negative conversion-rate and higher death rate than patients who were resistant to less than 5 drugs.

A multicenter phase II study of carboplatin and paclitaxel with a biweekly schedule in patients with advanced non-small-cell lung cancer: Kyushu thoracic oncology group trial.

PURPOSE: This multicenter phase II study was conducted to investigate the efficacy and safety of carboplatin in combination with paclitaxel administered according to a biweekly schedule as a first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligibility criteria included histologically or cytologically confirmed NSCLC (stage IIIb or IV), no prior treatment, and measurable or evaluable disease. Paclitaxel (140 mg/m(2)) was administered intravenously on day 1, in combination with carboplatin at an area under the concentration time curve (AUC) of 3, every 2 weeks. RESULTS: Seventy-four patients (45 men) with a median age of 62 years (range 40-74) and a median ECOG performance status of 1 (range 0-2) were enrolled. The response rate was 35.1% [95% confidence interval (CI): 24.4-47.1%], with 26 partial responses. The median survival was 357 days, and the median time to progression was 218 days. Toxicity was generally mild; National Cancer Institute-Common Toxicity Criteria (NCI-CTC) grades 3 and 4 neutropenia was observed in 50.0% of the patients, and grades 3 and 4 nausea/vomiting in 4.1%. CONCLUSIONS: Biweekly carboplatin combined with paclitaxel demonstrated anti-tumor activity in advanced NSCLC, with response and survival rates similar to those of carboplatin combined with paclitaxel administered every 3 weeks but with a more favorable toxicity profile, and the present data indicate that the regimen is suitable for use on an outpatient basis.

Increased circulating levels of soluble Fas ligand are correlated with disease activity in patients with fibrosing lung diseases.

OBJECTIVE: The Fas-Fas ligand (FasL) pathway is one of the important apoptosis-signalling molecule systems. We previously determined that this pathway may be involved in the pathogenesis of fibrosing lung diseases. In the present study, we evaluated the clinical significance of the levels of soluble forms of Fas (sFas) and FasL (sFasL) in serum from patients with fibrosing lung diseases. METHODOLOGY: We measured sFas, sFasL, KL-6 (a measure of alveolar type II cell damage), surfactant protein D (SP-D), and surfactant protein A (SP-A) levels in serum from 35 patients with idiopathic pulmonary fibrosis (IPF), 17 patients with interstitial pneumonia associated with collagen vascular diseases (CVD-IP), and 13 normal healthy controls using enzyme-linked immunosorbent assays (ELISA). RESULTS: The serum levels of sFasL were significantly increased in patients with active IPF and CVD-IP, compared with those with inactive disease and controls. There was no significant difference in sFasL levels between patients with inactive disease and controls. Serum sFasL levels were significantly correlated with lactate dehydrogenase and KL-6 levels in IPF. The decrease in sFasL levels following corticosteroid therapy was not correlated with the clinical course of IPF. There was no significant difference in serum sFas levels between IPF or CVD-IP patients and controls. CONCLUSIONS: Although further studies need to be performed on a large number of patients with histologically proven IPF or CVD-IP, it would seem that serum sFasL levels may reflect the activity of IPF and CVD-IP.

[Clinical investigation of pulmonary Mycobacterium kansasii infection in our hospital].

There is evidence that the number of non-tuberculous mycobacterium (NTM) cases is increasing at least in some areas of the world and as possible causes of the increase, the followings are pointed out; ageing of the population, improved methods for detecting organisms from clinical specimens, increased physician's awareness on the disease, increased exposure of patients to the source of the organism. In Japan, it has been estimated that the overall incidence of NTM disease is about 3 per 100,000. About 80% of NTM are MAC, and among the remainder, Mycobacterium kansasii is most common in our country. Our hospital located in Fukuoka prefecture in Kyushu, western part of Japan. In this study, clinical data of 24 cases of pulmonary infection caused by Mycobacterium kansasii in our hospital, from 1996 to 2000 were investigated. Primary infection type patients were younger than secondary infection type. Nearly all secondary infection type patients had underlying diseases and complications. Serum total protein and albumin in primary type is lower than that in secondary type. The results of mycobacterial drug sensitivity tests were as follows; for rifampicin, 23 cases were sensitive to 10 micrograms/ml, all cases to 50 micrograms/ml, for ethambutol, 15 cases were sensitive to 2.5 micrograms/ml, 22 cases to 5 micrograms/ml, and for isoniazid, all cases were resistant to 0.1 microgram/ml, 11 cases were sensitive to 1 microgram/ml and 23 cases to 5 micrograms/ml. Sputum cultures of patients treated with drug regimens containing RFP converted to negative within 2 months after starting chemotherapy. Although three patients with serious complications died, other 21 patients improved and showed no relapse at least 6 months after the completion of treatment.