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Biomedical subjects

Takayuki Kuriyama

Publications and source records attributed to Takayuki Kuriyama.

At least 19 recordsLinked to original sources

Phase II trial of amrubicin for treatment of refractory or relapsed small-cell lung cancer: Thoracic Oncology Research Group Study 0301.

PURPOSE: This multicenter, phase II study was conducted to evaluate the activity of amrubicin, a topoisomerase II inhibitor, against refractory or relapsed small-cell lung cancer (SCLC). PATIENTS AND METHODS: SCLC patients with measurable disease who had been treated previously with at least one platinum-based chemotherapy regimen and had an Eastern Cooperative Oncology Group performance status of 0 to 2 were eligible. Two groups of patients were selected: patients who experienced first-line treatment failure less than 60 days from treatment discontinuation (refractory group), and patients who responded to first-line treatment and experienced disease progression > or = 60 days after treatment discontinuation (sensitive group). Amrubicin was administered as a 5-minute daily intravenous injection at a dose of 40 mg/m2 for 3 consecutive days, every 3 weeks. RESULTS: Between June 2003 and December 2004, 60 patients (16 refractory and 44 sensitive) were enrolled. The median number of treatment cycles was four (range, one to eight). Grade 3 or 4 hematologic toxicities comprised neutropenia (83%), thrombocytopenia (20%), and anemia (33%). Febrile neutropenia was observed in three patients (5%). Nonhematologic toxicities were mild. No treatment-related death was observed. The overall response rates were 50% (95% CI, 25% to 75%) in the refractory group, and 52% (95% CI, 37% to 68%) in the sensitive group. The progression-free survival, overall survival, and 1-year survival in the refractory group and the sensitive group were 2.6 and 4.2 months, 10.3 and 11.6 months, and 40% and 46%, respectively. CONCLUSION: Amrubicin exhibits significant activity against SCLC, with predictable and manageable toxicities; this agent deserves to be studied more extensively in additional trials.

Aged↗

Predictive indicators of deep venous thrombosis and pulmonary arterial thromboembolism in 54 subjects after total knee arthroplasty using multislice computed tomography in logistic regression models.

PURPOSE: To determine predictors of deep venous thrombosis (DVT) in the lower extremities and pulmonary arterial thromboembolism (PE) after total knee arthroplasty (TKA), we evaluated the incidence of these events using multislice computed tomography (CT). METHODS: 54 subjects (10 males, 53-81 years old, the first consecutive 25 receiving anticoagulant therapy) underwent enhanced multislice CT (MSCT) before and one week after TKA. RESULTS: DVT, PE, and both were detected in twelve, twelve, and three subjects, respectively, one week after TKA. Hemoglobin and alveolar-arterial oxygen gradient (AaDO2) on the day after TKA, and total amount of operative bleeding (TAOB) were significantly higher in subjects with DVT or PE (P<0.05). In a logistic model for predicting DVT or PE, hemoglobin and AaDO2 levels on the day after TKA and TAOB were associated with an increased incidence of DVT or PE (relative risks 3.51, 1.19 and 1.01 (P<0.05), respectively). From box and whisker plots, we speculated the significant border to predict DVT or PE as 10.5 g/dl for hemoglobin, 34 Torr for AaDO2, and 1280 ml for TAOB. These factors also predicted DVT or PE (relative risks 5.08 (hemoglobin more than 10.5), 6.25 (AaDO2 more than 34 Torr), and 4.95 (TAOB more than 1280 ml) (P<0.05)). CONCLUSIONS: The incidence of DVT or PE one week after TKA was 39% by MSCT. High levels of TAOB, hemoglobin and AaDO2 on the day after TKA may be predictive indicators of DVT or PE one week after TKA.

Aged↗

Involvement of p38alpha mitogen-activated protein kinase in lung metastasis of tumor cells.

To study the role of p38 mitogen-activated protein kinase (p38) activity during the process of metastasis, p38alpha(+/-) mice were subjected to an in vivo metastasis assay. The number of lung colonies of tumor cells intravenously injected in p38alpha(+/-) mice was markedly decreased compared with that in wild-type (WT) mice. On the other hand, the time-dependent increase in tumor volume after subcutaneous tumor cells transplantation was comparable between WT and p38alpha(+/-) mice. Platelets of p38alpha(+/-) mice were poorly bound to tumor cells in vitro and in vivo compared with those of WT mice. E- and P-selectin mRNAs were markedly induced in the lung after intravenous injection of tumor cells. However, the induction of these selectin mRNAs in p38alpha(+/-) mice was weaker than that in WT mice. Furthermore, the resting expression levels of E-selectin in lung endothelial cells and P-selectin in platelets of p38alpha(+/-) mice were suppressed compared with those of WT mice. The number of tumor cells attached on lung endothelial cells of p38alpha(+/-) mice was significantly reduced compared with that of WT mice. The transmigrating activity of tumor cells through lung endothelial cells of p38alpha(+/-) mice was similar to that of WT mice. These results suggest that p38alpha plays an important role in extravasation of tumor cells, possibly through regulating the formation of tumor-platelet aggregates and their interaction with the endothelium involved in a step of hematogenous metastasis.

Animals↗

Diagnostic and therapeutic strategy for acute pulmonary thromboembolism.

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 V(1-3) 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.

Acute Disease↗

Basaloid squamous-cell carcinoma of the lung in a young woman.

We report a rare case of basaloid squamous cell carcinoma of the lung in a young Japanese woman. An 18-year-old woman presented with productive cough. Chest radiogram and computed tomography (CT) revealed a tumor in the left hilum accompanied by partial atelectasis of the left upper lobe and pleural effusion. Transbronchial fine-needle aspiration cytology supported a tentative diagnosis of primary squamous-cell carcinoma of the lung. The clinical stage was T4N2M1, with multiple bone metastases. Despite a transient response to chemotherapy consisting of carboplatin and paclitaxel, the patient died because of tumor progression 2 months after the start of the chemotherapy. Necropsy established the diagnosis of basaloid squamous-cell carcinoma of the lung. Immunohistochemical studies of the necropsy specimen indicated that the tumor was positive for keratin, vimentin, and S100, and negative for chromogranin A, cytokeratin CAM5.2, and bcl-2. Besides the rarity of the disease itself, the present case seemed to have additional uniqueness in that the patient was 18 years old and female. This is the youngest patient with a case of basaloid squamous cell carcinoma of the lung ever reported.

Adolescent↗

Risk factors of acute pulmonary thromboembolism in Japanese patients hospitalized for medical illness: results of a multicenter registry in the Japanese society of pulmonary embolism research.

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.

Aged↗

Acute pulmonary embolism after an earthquake in Japan.

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 < 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).

Acute Disease↗

Chronic pulmonary complications associated with toxic epidermal necrolysis: report of a severe case with anti-Ro/SS-A and a review of the published work.

Patients with toxic epidermal necrolysis (TEN) have been known to have various complications. Though pulmonary complications are often observed, they usually show an acute form; however, chronic complications are quite rare and little is known about either their incidences or clinical manifestations. We herein report a 33-year-old man who presented with chronic pulmonary complications after a recovery from TEN. At the onset of TEN, he had severe respiratory failure and artificial ventilation was instituted. Despite being extubated successfully, respiratory failure reappeared 1 month later. A diagnosis of chronic bronchitis with severe obstructive ventilatory impairment and bronchiectasis was made and he was treated with steroids, bronchodilators and antibiotics, however, he died 1.5 years after the onset of TEN. There have been 13 reported cases of chronic pulmonary complications with TEN or Stevens-Johnson syndrome (SJS) in the English published work. Such cases are usually classified into chronic bronchitis/bronchiolitis with obstructive change (including bronchiolitis obliterans and bronchiolitis obliterans organizing pneumonia), respiratory tract obstruction and bronchiectasis. Approximately 40% of all such patients die while the surviving continue to suffer from these complications because no curative therapy yet exists. As a result, the prognosis seems to be poor. The relationship between TEN and these chronic pulmonary complications remains to be elucidated. Interestingly, our patient was asymptomatically anti-Ro/SS-A positive at the onset of TEN. In addition, eccrine gland involvement and an extremely high level of serum salivary amylase were observed at the onset of TEN, furthermore, Sjögren-like symptoms occurred after recovery from TEN. These findings suggested that the Sjögren-like autoimmune abnormalities induced by anti-Ro/SS-A correlated with the development of chronic pulmonary complications in our patient.

Adult↗

Drug-resistant genes and serotypes of pneumococcal strains of community-acquired pneumonia among adults in Japan.

BACKGROUND: A high frequency of drug-resistant pneumococci has been reported in Asian countries. Few data on the drug-resistance or serotype of pneumococcal strains responsible for community-acquired pneumonia (CAP), however, are available for the past two decades in Japan. METHODOLOGY: Susceptibility to antibiotics and the genotype of antibiotic-resistant genes and serotypes of Streptococcus pneumoniae isolates from 114 adult patients with CAP were examined in a nationwide study in Japan between 2001 and 2003. RESULTS: Most of the cases were non-bacteraemic pneumonia and the case fatality rate was 4.4%. The most frequent genotype of the pbp gene was pbp1a + 2x + 2b (gPRSP; 36.8%) followed by pbp 2x (28.1%) and of the macrolide-resistant gene, it was ermB (50.0%). The most common serotype was 19F (29.1%), followed by serotype 23F (13.2%), 6B (12.3%) and 3 (11.4%). The coverage of serotypes of isolates by a 23-valent pneumococcal polysaccharide vaccine (PPV) would be 82.5% in these patients with CAP. Most of strains with serotypes 19F and 23F were gPRSP. A cluster of serotype 3 strains associated with the pbp 2x and ermB gene was also noted. CONCLUSION: A high frequency of altered pbp gene mutations or of macrolide-related genes and a high serotype coverage by the 23-valent PPV found in our study of pneumococcal pneumonia facilitates attempts to increase the coverage rate of the 23-valent PPV in adults older than 65 years in Japan.

Adult↗

Angiotensin-converting enzyme gene polymorphisms and prognosis in chronic thromboembolic pulmonary hypertension.

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 (II, 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.

Adult↗

Breakdown of mucosal immunity in the gut and resultant systemic sensitization by oral antigens in a murine model for systemic lupus erythematosus.

Secreted IgA plays a pivotal role in the mucosal immunity to maintain the front line of body defense. We found that the level of fecal IgA was dramatically decreased in aged (NZB x NZW)F(1) (BWF(1)) mice developing lupus nephritis, whereas levels in similarly aged New Zealand Black (NZB) and New Zealand White (NZW) mice remained unchanged compared with young mice. The number of cells obtained from Peyer's patches was markedly decreased in aged BWF(1) mice. Aged BWF(1) mice showed increased susceptibility to pathogenic bacterial infection. Furthermore, oral administration of OVA failed to inhibit secondary IgG response induced by systemic immunization, suggesting defective oral tolerance in aged BWF(1) mice. A significant amount of orally administered OVA was incorporated directly into the intestinal lamina propria in aged BWF(1) mice whereas it was mainly localized in subepithelial domes and interfollicular region in Peyer's patches in young mice. T cells obtained from renal and pulmonary lymph nodes of aged BWF(1) mice that had been orally administered with OVA showed an Ag-specific T cell proliferation, whereas those from young BWF(1), aged NZB, and aged NZW mice did not. Interestingly, aerosol exposure to OVA of aged BWF(1) mice, which had been orally administered with the same Ag, provoked an eosinophil infiltration in the lung. These results demonstrate that mucosal immunity in the gut is impaired and oral Ags induce systemic sensitization instead of oral tolerance in the development of murine lupus.

Administration, Inhalation↗

Effectiveness and safety of the thrombolytic therapy for acute pulmonary thromboembolism: results of a multicenter registry in the Japanese Society of Pulmonary Embolism Research.

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.

Acute Disease↗

Phase I study of cisplatin and irinotecan combined with concurrent hyperfractionated accelerated thoracic radiotherapy for locally advanced non-small cell lung carcinoma.

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.

Aged↗

A murine model of pulmonary basidiomycosis by Schizophyllum commune.

Schizophyllum commune has recently emerged as a causative agent of human mycosis, but the details of its virulence are not yet known. To elucidate the pathogenicity of S. commune, a murine model of invasive pulmonary infection was established. ICR mice, not immunosuppressed or immunosuppressed by cortisone acetate, were infected with S. commune by intratracheal inoculation with agar beads containing the basidiospores. All immunosuppressed mice died within 2 weeks. Pathology examination revealed massive mycelial invasion into the lungs, penetration into adjacent vessels, and systemic dissemination, suggesting much higher virulence of this fungus than was previously estimated. This is the first murine model of pulmonary infection by S. commune, which we believe can be of assistance during subsequent investigations of this infection.

Animals↗

Metabolic activity in skeletal muscles of patients with non-hypoxaemic chronic obstructive pulmonary disease studied by 31P-magnetic resonance spectroscopy.

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.

Aged↗

Clinical characteristics, diagnosis and management of patients with pulmonary thromboembolism who are not diagnosed in the acute phase and not classified as chronic thromboembolic pulmonary hypertension.

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.

Adult↗

Effects of the endothelin receptor antagonist bosentan on hemodynamics, symptoms and functional capacity in Japanese patients with severe pulmonary hypertension.

BACKGROUND: Endothelin (ET)-1 has a pathogenic role in pulmonary arterial hypertension (PAH). Recent clinical studies carried out in Western populations showed that blockade of the ET receptors by bosentan improves pulmonary hemodynamics and exercise capacity. In the present study, the efficacy of bosentan was assessed in Japanese patients with PAH. METHOD AND RESULTS: Because the pharmacokinetics of bosentan and its metabolites are similar in Japanese and Caucasian subjects, the same dose of bosentan, 125 mg twice daily, was administered in the Japanese open-label clinical trial. In 18 patients, mean pulmonary arterial pressure decreased from 52.4+/-13.8 to 46.8+/-13.8 mmHg (p=0.003) and cardiac index increased from 2.20+/-0.74 to 2.61 +/-0.72 L.min(-1).m(-2) (p=0.002). The 6-min walking distance increased from 410+/-89.5 to 494+/-86.0 m (p<0.0001). The dyspnea index (Borg scale) decreased from 3.2+/-2.4 to 2.2+/-1.7 (p=0.02). The specific activity scale (SAS) gradually increased throughout the study period from 2.9+/-0.8 to 4.6+/-1.9 METs (p=0.0005). WHO Class improved in 10 patients. CONCLUSION: Bosentan was well tolerated and improved the hemodynamics, symptoms, exercise capacity, and quality of life of Japanese patients with PAH. Thus, bosentan can be a valuable therapeutic option in Japanese patients.

Adult↗