130 research outputs found

    Effect of denosumab on Japanese patients with rheumatoid arthritis: a dose-response study of AMG 162 (Denosumab) in patients with RheumatoId arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE)-a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial

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    OBJECTIVES: To evaluate efficacy and safety of three different regimens of denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor kappa B (RANK) ligand (RANKL), for Japanese patients with rheumatoid arthritis (RA). METHODS: In this multicentre, randomised, placebo-controlled phase II study, 350 Japanese patients with RA between 6 months and <5 years, stratified by glucocorticoid use and rheumatoid factor status, were randomly assigned to subcutaneous injections of placebo or denosumab 60 mg every 6 months (Q6M), every 3 months (Q3M) or every 2 months (Q2M). All patients basically continued methotrexate treatment and had a supplement of calcium and vitamin D throughout the study. The primary endpoint was change in the modified Sharp erosion score from baseline to 12 months. RESULTS: Denosumab significantly inhibited the progression of bone erosion at 12 months compared with the placebo, and the mean changes of the modified Sharp erosion score at 12 months from baseline were 0.99, 0.27 (compared with placebo, p=0.0082), 0.14 (p=0.0036) and 0.09 (p<0.0001) in the placebo, Q6M, Q3M and Q2M, respectively. Secondary endpoint analysis revealed that denosumab also significantly inhibited the increase of the modified total Sharp score compared with the placebo, with no obvious evidence of an effect on joint space narrowing for denosumab. As shown in previous studies, denosumab increased bone mineral density. No apparent difference was observed in the safety profiles of denosumab and placebo. CONCLUSIONS: Addition of denosumab to methotrexate has potential as a new therapeutic option for patients with RA with risk factors of joint destruction. TRIAL REGISTRATION NUMBER: JapicCTI-101263

    Robot As Moral Agent: A Philosophical and Empirical Approach

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    平成29年7月29日 CogSci 2017 : London, Hilton Hotel Metropole, London, England, における発表資

    Relationship between Intracellular Signaling of the (Pro)renin Receptor and the Pathogenesis of Preeclampsia

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    An association between preeclampsia and (pro)renin was recently reported. Intracellular signaling of the (pro) renin receptor [(P)RR] increases the expressions of TGF-β and PAI-1. In this study we sought to clarify the involvement of (pro)renin in the pathogenesis of preeclampsia via the intracellular signaling of (P)RR on preeclampsia placentas. Activated (pro)renin plasma concentrations were compared between pregnant women with (n=15) and without (n=28) preeclampsia. The placentas were immunohistochemically evaluated with anti-HIF-1α and anti-(P)RR antibodies. HTR-8/SVneo cells were cultured under hypoxic conditions and treated with human recombinant (pro)renin. The mRNA expressions of HIF-1α, (P)RR, PAI-1, TGF-β, and ET-1 were also examined by real-time RCR. The activated (pro)renin plasma concentration was significantly higher in the third vs. the second trimester in the preeclampsia patients. HIF-1α and (P)RR expressions were significantly increased in the preeclampsia placentas. The mRNA expressions of PAI-1, TGF-β, and ET-1 were significantly increased in the experiments using recombinant (pro)renin vs. hypoxic conditions. (P)RR expression in preeclampsia placentas is increased by persistent hypoxia through the second and third trimesters, and PAI-1, TGF-β, and ET-1 production is increased via (P)RR. Our results suggest that ET-1 production via the intracellular signaling of (P)RR is important in the pathogenesis of preeclampsia

    Impact of laparoscopic surgery on short‐term and long‐term outcomes in elderly obese patients with colon cancer

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    [Background] Laparoscopic surgery is reported to be useful in obese or elderly patients with colon cancer, who are at increased risk of postoperative complications because of comorbidities and physical decline. However, its usefulness is less clear in patients who are both elderly and obese and may be at high risk of complications. [Methods] Data for obese patients (body mass index ≥25) who underwent laparoscopic or open surgery for stage II or III colon cancer between January 2009 and December 2013 were collected by the Japan Society of Laparoscopic Colorectal Surgery. Surgical outcomes, postoperative complications, and relapse-free survival (RFS) were compared between patients who underwent open surgery and those who underwent laparoscopic surgery according to whether they were elderly (≥70 y) or nonelderly (<70 y). [Results] Data of 1549 patients (elderly, n = 598; nonelderly, n = 951) satisfied the selection criteria for analysis. Length of stay was shorter and surgical wound infection was less common in elderly obese patients who underwent laparoscopic surgery than in those underwent open surgery. There were no significant between-group differences in overall complications, anastomotic leakage, ileus/small bowel obstruction, or RFS. There were also no significant differences in RFS after laparoscopic surgery according to patient age. [Conclusion] Laparoscopic surgery is safe in elderly obese patients with colon cancer and does not worsen their prognosis. There was no significant difference in the effectiveness of laparoscopic surgery between obese patients who were elderly and those who were nonelderly

    Association between markers of arterial stiffness and atrial fibrillation in the Circulatory Risk in Communities Study (CIRCS).

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    Background and aims:Limited evidence is available on the association between markers of arterial stiffness and the prevalence of atrial fibrillation among Asian populations. Therefore, we examined those associations in the Japanese population.Methods:We conducted a cross-sectional population-based study of 4264 men and women aged 40-79 years. The augmentation index (AI), a marker of arterial stiffness, was calculated as the ratio of central pulse pressure/brachial pulse pressure, where the AI and central aortic pressure were measured by an automated tonometer: the HEM-9000AI device (Omron Healthcare co., Kyoto, Japan). Atrial fibrillation was estimated by the Minnesota codes using resting electrocardiograph (ECG).Results:The prevalence of atrial fibrillation and total arrhythmia were higher with larger AI values. These associations did not change after adjustment for known cardiovascular risk factors. The multivariable odd ratios (95% confidence intervals) in the highest versus lowest tertiles of AI were 3.4 (1.4-8.6, p for trend = 0.008) for atrial fibrillation and 1.8 (1.2-2.7, p for trend = 0.004) for total arrhythmia. There was no association of central or brachial pulse pressure levels with the prevalence of atrial fibrillation or total arrhythmia.ConclusionAI values, but not brachial or central pulse pressures, were positively associated with the prevalence of atrial fibrillation and total arrhythmia, independent of cardiovascular risk factors

    External Pancreatic Juice Drainage Through a Percutaneous Endoscopic Drainage Tube for the Patient With a Postoperative Pancreatic Juice Leakage

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    Percutaneous endoscopic gastrostomy (PEG) has been widely accepted for patients who have no swallowing ability but have an intact gut. Its clinical application is mainly for nutritional support and decompression of the intestine in patients with bowel obstruction. In this paper, we report external pancreatic juice drainage through a percutaneous endoscopic drainage tube in a patient with postoperative pancreatic juice leakage. Soon after this procedure, pancreatic juice leakage subsided. This procedure was minimally invasive for the patient and may be a new application of PEG to maintain the good quality of life (QOL) in a patient with pancreatic juice leakage
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