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Tsujita K.,Kumamoto University | Sugiyama S.,Diabetes Care Center | Sumida H.,Kumamoto Central Hospital | Shimomura H.,Fukuoka Tokushukai Medical Center | And 23 more authors.
Journal of the American College of Cardiology | Year: 2015

Background Despite standard statin therapy, a majority of patients retain a high "residual risk" of cardiovascular events. Objectives The aim of this study was to evaluate the effects of ezetimibe plus atorvastatin versus atorvastatin monotherapy on the lipid profile and coronary atherosclerosis in Japanese patients who underwent percutaneous coronary intervention (PCI). Methods This trial was a prospective, randomized, controlled, multicenter study. Eligible patients who underwent PCI were randomly assigned to atorvastatin alone or atorvastatin plus ezetimibe (10 mg) daily. Atorvastatin was uptitrated with a treatment goal of low-density lipoprotein cholesterol (LDL-C) <70 mg/dl. Serial volumetric intravascular ultrasound was performed at baseline and again at 9 to 12 months to quantify the coronary plaque response in 202 patients. Results The combination of atorvastatin/ezetimibe resulted in lower levels of LDL-C than atorvastatin monotherapy (63.2 ± 16.3 mg/dl vs. 73.3 ± 20.3 mg/dl; p < 0.001). For the absolute change in percent atheroma volume (PAV), the mean difference between the 2 groups (-1.538%; 95% confidence interval [CI]: -3.079% to 0.003%) did not exceed the pre-defined noninferiority margin of 3%, but the absolute change in PAV did show superiority for the dual lipid-lowering strategy (-1.4%; 95% CI: -3.4% to -0.1% vs. -0.3%; 95% CI: -1.9% to 0.9% with atorvastatin alone; p = 0.001). For PAV, a significantly greater percentage of patients who received atorvastatin/ezetimibe showed coronary plaque regression (78% vs. 58%; p = 0.004). Both strategies had acceptable side effect profiles, with a low incidence of laboratory abnormalities and cardiovascular events. Conclusions Compared with standard statin monotherapy, the combination of statin plus ezetimibe showed greater coronary plaque regression, which might be attributed to cholesterol absorption inhibition-induced aggressive lipid lowering. (Plaque Regression With Cholesterol Absorption Inhibitor or Synthesis Inhibitor Evaluated by Intravascular Ultrasound [PRECISE-IVUS]; NCT01043380) © 2015 American College of Cardiology Foundation. Source


Nakamura T.,Japan Labor Health and Welfare Organization | Suemitsu K.,The Mutual
Journal of Vascular Surgery | Year: 2014

Objective The Japanese Society for Dialysis Therapy recommends superficialization of the brachial artery (BA) as an alternative vascular access (VA) technique in patients for whom a conventional internal shunt (arteriovenous fistula [AVF] or arteriovenous graft) cannot be created. Although 2% to 3% of Japanese hemodialysis patients undergo this procedure, it is not well recognized worldwide. We report here our experience with the procedure, as well as indications, durability, and morbidity. Methods The technique involves exposure of the BA and ligation of the side branches, then fixing it beneath the skin at the upper arm. Cannulation of the BA is performed 2 weeks or more after surgery, and it is used as an outflow route, with any vein in an upper extremity utilized for blood return, including the hand if sites in the arm are not accessible. We retrospectively reviewed our cases of superficialization of the BA for VA. Results From 2005 through 2008, a total of 24 patients (11 females [46%]; average age, 69 years [range, 39-84 years]) underwent superficialization of the BA, of whom eight (33%) had diabetes. The indications were (1) impaired cardiac function (n = 13); (2) no other prospect for AVF or patient refused prosthetic graft implantation (n = 5); (3) severe upper extremity arterial disease or ischemic steal syndrome requiring AVF closure (n = 3); (4) venous hypertension with central vein occlusion (n = 2); and (5) repeated AVF thrombosis due to heparin-induced thrombocytopenia (n = 1). The mean follow-up period was 28 months. Serious complications were seen in one patient with an infected pseudoaneurysm formation associated with a BA puncture, which necessitated BA ligation, while two patients required an aneurysmectomy with reconstruction and one had occlusion of the superficialized BA, though no clinical symptoms of hand ischemia developed. We also had difficulty finding a vein for blood return in five patients. The rate of superficialized BA patency as a functioning VA was 95% and 66% at 1 and 3 years, respectively. Conclusions Superficialization of the BA was found to be a simple and safe technique, with acceptable durability and complication rate in selected Japanese hemodialysis patients. We consider that this shuntless VA permits adequate blood flow and has theoretical advantages for some patients, particularly those with impaired cardiac function, though the availability of a return vein is a prerequisite for a functioning VA. Copyright © 2014 by the Society for Vascular Surgery. Source


Yoshida M.,Japan Labor Health and Welfare Organization | Masunaga K.,Tokyo Metropolitan Geriatric Hospital | Nagata T.,Toshiba Hospital | Satoji Y.,Kumamoto University | Shiomi M.,Kobe University
Neurourology and Urodynamics | Year: 2010

Aims: Lower urinary tract symptoms (LUTS) are common in the aging population. LUTS cause profoundly negative impacts on their quality of life. Pathophysiology of LUTS is multifactorial, and recently, bladder ischemia and metabolic syndrome have been suggested as etiological factors. To evaluate chronic hyperlipidemia on bladder function, we examined the functional and histological changes of the bladder in myocardial infarction-prone Watanabe Heritable Hyperlipidemic (WHHLMI) rabbits. Methods: 20- to 24-month-old WHHLMI rabbits and ageand sex-matched control rabbits were prepared. Bladder functions were evaluated using cystometrograms and functional experiments with isolated bladder specimens. Histological studies of bladder and internal iliac arteries were performed with hematoxylin and eosin staining. The bladder was also stained immunohistochemically with mouse monoclonal S-100 antibodies and sheep polyclonal calcitonin gene-related peptide (CGRP) antibodies. Results: In cystometric examination, WHHLMI rabbits showed significantly shorter micturition interval, smaller voided volume with non-voiding contractions, and lower micturition pressure, as compared to control. The functional experiments showed that carbachol- and electrical field stimulation-induced contractions were significantly decreased in WHHLMI rabbits than those in control. In WHHLMI rabbits, cross-sections of internal iliac arteries showed significant atherosclerosis and thickening of media. Bladder showed thinner urothelium and decreased smooth muscle area in WHHLMI rabbits, as compared to control. WHHLMI rabbits showed a significant decrease in S-100 protein positive neurons, and an increased number of CGRP positive neurons. Conclusions: This study demonstrated that WHHLMI rabbits showed detrusor overactivity with decreased detrusor contraction. It is suggested that chronic hyperlipidemia contributes to the bladder dysfunction. © 2010 Wiley-Liss, Inc. Source


Yoshida M.,Japan Labor Health and Welfare Organization | Kudoh J.,Japan Labor Health and Welfare Organization | Homma Y.,University of Tokyo | Kawabe K.,Tokyo Teishin Hospital
Clinical Interventions in Aging | Year: 2011

Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) are highly prevalent in older men. Medical therapy is the first-line treatment for LUTS associated with BPH. Mainstays in the treatment of male LUTS and clinical BPH are the α 1-adrenergic receptor antagonists. Silodosin is a new α 1-adrenergic receptor antagonist that is selective for the α 1A-adrenergic receptor. By antagonizing α 1A-adrenergic receptors in the prostate and urethra, silodosin causes smooth muscle relaxation in the lower urinary tract. Since silodosin has greater affinity for the α 1A-adrenergic receptor than for the α 1B-adrenergic receptor, it minimizes the propensity for blood pressure-related adverse effects caused by α 1B-adrenergic receptor blockade. In the clinical studies, patients receiving silodosin at a total daily dose of 8 mg exhibited significant improvements in the International Prostate Symptom Score and maximum urinary flow rate compared with those receiving placebo. Silodosin showed early onset of efficacy for both voiding and storage symptoms. Furthermore, long-term safety of silodosin was also demonstrated. Retrograde or abnormal ejaculation was the most commonly reported adverse effect. The incidence of orthostatic hypotension was low. In conclusion, silodosin, a novel selective α 1A-adrenergic receptor antagonist, was effective in general and without obtrusive side effects. This review provides clear evidence in support of the clinical usefulness of silodosin in the treatment of LUTS associated with BPH. © 2011 Yoshida et al, publisher and licensee Dove Medical Press Ltd. Source


Yoshida M.,Japan Labor Health and Welfare Organization | Kudoh J.,Japan Labor Health and Welfare Organization | Homma Y.,University of Tokyo | Kawabe K.,Tokyo Teishin Hospital
International Journal of Urology | Year: 2012

Lower urinary tract symptoms associated with benign prostatic hyperplasia are highly prevalent in older men. Pharmacological treatment is the first-line treatment for lower urinary tract symptoms associated with benign prostatic hyperplasia. The first choice in the pharmacological treatment for lower urinary tract symptoms associated with benign prostatic hyperplasia is the α 1-adrenoceptor antagonists. Many α 1-adrenoceptor antagonists are available in the world. Silodosin is an α 1-adrenoceptor antagonist developed by Kissei Pharmaceutical, and has a specific selectivity for the α 1A-adrenoceptor subtype. By antagonizing α 1A-adrenoceptor in the prostate and urethra, silodosin causes smooth muscle relaxation in the lower urinary tract. As a result of the high affinity for the α 1A-adrenoceptor than for the α 1B-adrenoceptor, silodosin minimizes the propensity for blood pressure-related adverse effects caused by blockade of α 1B-adrenoceptor. The efficacy and safety of silodosin for treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia was first reported by Japanese investigators in 2006. At present, silodosin is used in many countries. In the present review, we summarize the new clinical evidence for lower urinary tract symptoms associated with benign prostatic hyperplasia and introduce the data supporting the new clinical indications of silodosin. © 2012 The Japanese Urological Association. Source

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