Shinmatsudo Central General Hospital


Shinmatsudo Central General Hospital


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Nakamura T.,Shinmatsudo Central General Hospital | Yamagishi S.-I.,Kurume University
Current Molecular Medicine | Year: 2010

Septic shock is one of the leading causes of morbidity and mortality. Endotoxin plays an important role in the pathogenesis of septic shock. Lack of clinical success with anti-endotoxin or anti-cytokine therapies has shifted interest to extracorporeal therapies to reduce circulating levels of various mediators for septic shock patients. Polymyxin B -immobilized polystyrene fiber (PMX-F) is a medical device that aims to remove circulating endotoxin by adsorption. Since 1994, PMX-F column has been available in Japan, and many investigators have reported that PMX-F treatment is safe and effective in patients with septic shock. Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors. PEDF induces macrophages apoptosis and necrosis through the activation of peroxisome proliferator-activated receptor-gamma by which PEDF could modulate inflammatory reactions in septic shock. Further, given the fact that PEDF possesses anti-oxidative and anti-inflammatory properties in vivo, serum PEDF level may be a biomarker of septic shock. However, little is known about the relationship between serum level of PEDF and inflammatory biomarkers such as endotoxin and high mobility group box 1 (HMGB1) in septic shock and the effects of PMX-F treatment on these markers. This review aims to provide current knowledge about the pathogenesis of septic shock and the clinical utility of PMX-F treatment. We also discuss here the pathophysiological role of PEDF in this devastating disorder. © 2010 Bentham Science Publishers Ltd.

Nakamura T.,Shinmatsudo Central General Hospital | Sato E.,Shinmatsudo Central General Hospital | Amaha M.,Shinmatsudo Central General Hospital | Kawagoe Y.,Shinmatsudo Central General Hospital | And 2 more authors.
JRAAS - Journal of the Renin-Angiotensin-Aldosterone System | Year: 2012

Introduction: Tubular injury is more important than glomerulopathy for renal prognosis in chronic kidney disease (CKD) patients. Numerous studies have demonstrated the active participation of the renin-angiotensin system (RAS) in CKD. However, whether addition of aliskiren, a direct renin inhibitor, to olmesartan improves renal tubular injury in CKD patients is unknown.Methods: This study compared the effects of aliskiren (300 mg daily), olmesartan (40 mg daily), and its combination therapy on urinary L-fatty acid binding protein (L-FABP), a marker of tubular injury in stage I or II CKD patients. It also examined which clinical variables were independently correlated with tubular damage.Results: Olmesartan or aliskiren monotherapy for 6 months comparably decreased blood pressure (BP) and proteinuria. BP and proteinuria levels were reduced more by combination therapy than by either monotherapy. Olmesartan or aliskiren decreased urinary L-FABP level, and combination therapy produced more incremental reduction in L-FABP level relative to each monotherapy. Multiple stepwise regression analysis revealed that BMI, low-density lipoprotein (LDL)-cholesterol and proteinuria were independently related to urinary L-FABP level.Conclusions: The present study demonstrated that addition of aliskiren to olmesartan decreased urinary L-FABP level partly via reduction of proteinuria in stage I or II CKD patients. © The Author(s) 2011.

Nakamura T.,Shinmatsudo Central General Hospital | Sato E.,Shinmatsudo Central General Hospital | Fujiwara N.,Shinmatsudo Central General Hospital | Kawagoe Y.,Shinmatsudo Central General Hospital | And 2 more authors.
Clinical Biochemistry | Year: 2011

Objectives Receptor for advanced glycation end products (RAGE) plays a role in inflammatory reactions. Soluble RAGE (sRAGE) level is elevated in patients with acute respiratory distress syndrome (ARDS). However, which clinical parameters and inflammatory biomarkers including sRAGE are associated with death in ARDS patients remain unknown. Design and methods We examined whether sRAGE level was independently associated with death in 20 ARDS patients with severe infection. Results Compared with age- and sex-matched control subjects, blood pressure levels were lower and KL-6, high mobility group box 1 (HMGB1), interleukin-6 and sRAGE levels were higher in ARDS patients. In multivariate analysis, sRAGE was associated with death in ARDS patients, but severity of illness was not. HMGB1 was a sole independent correlate of sRAGE. Conclusions This study demonstrated that sRAGE was independently associated with death in ARDS patients. Our present results suggest active involvement of HMGB1-RAGE axis in poor prognosis of ARDS. © 2010 Elsevier B.V.

Nakamura T.,Shinmatsudo Central General Hospital | Sato E.,Shinmatsudo Central General Hospital | Fujiwara N.,Shinmatsudo Central General Hospital | Kawagoe Y.,Shinmatsudo Central General Hospital | And 3 more authors.
Metabolism: Clinical and Experimental | Year: 2011

AST-120 is an oral adsorbent that attenuates the progression of chronic renal failure (CRF) and improves the prognosis of the patients under dialysis. Although tubulointerstitial injury is more important than glomerulopathy in terms of renal prognosis in patients with CRF, effect of AST-120 on tubular injury in CRF patients remains unknown. In this study, we examined whether and how AST-120 treatment could improve tubular damage in nondiabetic CRF patients. Fifty nondiabetic CRF patients were enrolled in the present study and divided into 2 groups: one was the AST-120-treated group (15 men and 10 women) and the other was the age-, sex-, and clinical variables-matched non-AST-120-treated control group. Patients were followed up for 12 months. We investigated the effects of AST-120 on serum levels of interleukin-6 (IL-6), proteinuria, and urinary excretion levels of 8-hydroxydeoxyguanosine (8-OHdG) and L-fatty acid binding protein (L-FABP), markers of oxidative stress and tubular injury, respectively. AST-120 treatment (6 g/d), but not control treatment, for 12 months significantly reduced IL-6, proteinuria, and urinary excretion levels of L-FABP and 8-OHdG, and inhibited the increase in serum creatinine in CRF patients. In univariate analyses, L-FABP levels were correlated with age, proteinuria, 8-OHdG, and IL-6. In multiple stepwise regression analysis, proteinuria and urinary 8-OHdG levels were independently related to L-FABP levels (R2 = 0.605). Our present study demonstrated for the first time that AST-120 improved tubular injury in nondiabetic CRF patients. AST-120 may exert beneficial effects in CRF patients by protecting tubular damage partly via reduction of proteinuria and oxidative stress generation. © 2011 Elsevier Inc. All rights reserved.

Toyoda H.,Ogaki Municipal Hospital | Kumada T.,Ogaki Municipal Hospital | Takaguchi K.,Kagawa Prefectural Central Hospital | Shimada N.,Shinmatsudo Central General Hospital | Tanaka J.,Hiroshima University
Epidemiology and Infection | Year: 2014

Genotypes are associated with the natural course of hepatitis C virus (HCV) infection and response to antiviral therapy for HCV. HCV genotype 1b has been the dominant genotype in Japan, where the prevention of HCV transmission through blood transfusion or nosocomial infection has been established since 1990. The distribution of HCV genotype was investigated based on patient's birth year in 5515 HCV-infected Japanese individuals at three institutions from different areas of Japan. At all three institutions, the proportion of HCV genotype 1b decreased and was <50% in individuals born after 1970. By contrast, the percentage of HCV genotype 2b increased in subsequent birth cohorts after 1920-1929. Significant changes in HCV genotype distribution were observed across Japan regardless of area. Copyright © 2014 Cambridge University Press.

Doi K.,Japan Science and Technology Agency | Noiri E.,Japan Science and Technology Agency | Maeda-Mamiya R.,Japan Science and Technology Agency | Ishii T.,Japan Science and Technology Agency | And 7 more authors.
Critical Care Medicine | Year: 2010

Objective: This study is aimed to examine whether urinary L-type fatty acid-binding protein can detect the severity of sepsis with animal sepsis models and septic shock patients complicated with established acute kidney injury. Design: Experimental animal models and a clinical, prospective observational study. Setting: University laboratory and tertiary hospital. Subjects and Patients: One hundred fourteen human L-type fatty acid-binding protein transgenic mice and 145 septic shock patients with established acute kidney injury. Interventions: Animals were challenged by abdominal (cecal ligation and puncture) and pulmonary (intratracheal lipopolysaccharide injection) sepsis models with different severities that were confirmed by survival analysis (n = 24) and bronchoalveolar lavage fluid analysis (n = 38). Measurements and main results: In animal experiments, significant increases of urinary L-type fatty acid-binding protein levels were induced by sepsis (severe cecal ligation and puncture 399.0 ± 226.8 μg/g creatinine [n = 12], less-severe cecal ligation and puncture 89.1 ± 25.3 [n = 11], sham 13.4 ± 3.4 [n = 10] at 6 hrs, p <.05 vs. sham; 200 μg of lipopolysaccharide 190.6 ± 77.4 μg/g creatinine [n = 6], 50 μg of lipopolysaccharide 145.4 ± 32.6 [n = 8], and saline 29.9 ± 14.9 [n = 5] at 6 hrs, p <.05 vs. saline). Urinary L-type fatty acid-binding protein predicted severity more accurately than blood urea nitrogen, serum creatinine, and urinary N-acetyl-d-glucosaminidase levels. In clinical evaluation, urinary L-type fatty acid-binding protein measured at admission was significantly higher in the nonsurvivors of septic shock with established acute kidney injury than in the survivors (4366 ± 192 μg/g creatinine [n = 68] vs. 483 ± 71 [n = 77], p <.05). Urinary L-type fatty acid-binding protein showed the higher value of area under the receiver operating characteristic curve for mortality compared with Acute Physiology and Chronic Health Evaluation (APACHE) II and Sepsis-related Organ Failure Assessment (SOFA) scores (L-type fatty acid-binding protein 0.994 [0.956-0.999], APACHE II 0.927 [0.873-0.959], and SOFA 0.813 [0.733-0.873], p <.05). Conclusions: Our results suggest that urinary L-type fatty acid-binding protein can be a useful biomarker for sepsis complicated with acute kidney injury for detecting its severity. © 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.

Yoshizawa K.,Jikei University School of Medicine | Abe H.,Jikei University School of Medicine | Aida Y.,Jikei University School of Medicine | Ishiguro H.,Jikei University School of Medicine | And 4 more authors.
Journal of Medical Virology | Year: 2013

Host lipoprotein metabolism is associated closely with the life cycle of hepatitis C virus (HCV), and serum lipid profiles have been linked to the response to pegylated interferon (Peg-IFN) plus ribavirin (RBV) therapy. Polymorphisms in the human IL28B gene and amino acid substitutions in the core and interferon sensitivity-determining region (ISDR) in NS5A of HCV genotype 1b (G1b) were also shown to strongly affect the outcome of Peg-IFN plus RBV therapy. In this study, an observational cohort study was performed in 247 HCV G1b-infected patients to investigate whether the response to Peg-IFN and RBV combination therapy in these patients is independently associated with the level of lipid factors, especially apolipoprotein B-100 (apoB-100), an obligatory structural component of very low density lipoprotein and low density lipoprotein. The multivariate logistic analysis subsequently identified apoB-100 (odds ratio (OR), 1.602; 95% confidence interval (CI), 1.046-2.456), alpha-fetoprotein (OR, 0.764; 95% CI, 0.610-0.958), non-wild-type ISDR (OR, 5.617; 95% CI, 1.274-24.754), and the rs8099917 major genotype (OR, 34.188; 95% CI, 10.225-114.308) as independent factors affecting rapid initial virological response (decline in HCV RNA levels by ≥3-log10 at week 4). While lipid factors were not independent predictors of complete early or sustained virological response, the serum apoB-100 level was an independent factor for sustained virological response in patients carrying the rs8099917 hetero/minor genotype. Together, we conclude that serum apoB-100 concentrations could predict virological response to Peg-IFN plus RBV combination therapy in patients infected with HCV G1b, especially in those with the rs8099917 hetero/minor genotype. © 2013 Wiley Periodicals, Inc.

Nakamura T.,Shinmatsudo Central General Hospital | Sato E.,Shinmatsudo Central General Hospital | Fujiwara N.,Shinmatsudo Central General Hospital | Kawagoe Y.,Shinmatsudo Central General Hospital | And 3 more authors.
American Journal of the Medical Sciences | Year: 2012

BACKGROUNDS: Autosomal dominant polycystic kidney disease (ADPKD) progresses more quickly to end-stage renal disease in patients with hypertension than in their normotensive counterparts. The authors investigated the effect of telmisartan versus enalapril on systolic and diastolic blood pressure (SBP and DBP), urinary albumin excretion (UAE), serum high mobility group box-1 protein (HMGB1), serum interleukin (IL)-6 and urinary 8-hydroxydeoxyguanosine (8-OHdG) levels in patients with hypertensive ADPKD. METHODS: Twenty patients with hypertensive ADPKD with good renal function were randomly assigned to 1 of 2 treatments: telmisartan 80 mg once daily (n = 10) or enalapril 10 mg once daily (n = 10). Treatment lasted 12 months. SBP, DBP, serum creatinine, UAE, HMGB1, IL-6 and urinary 8-OHdG levels were measured before and 6 and 12 months after treatment. RESULTS: Both SBP and DBP were significantly reduced after treatment (P < 0.001) in both groups. Serum creatinine changed little during the experimental period in either group. UAE, serum HMGB1, serum IL-6 and urinary 8-OHdG levels were significantly decreased after treatment (UAE, HMGB1 and IL-6, P < 0.001; and 8-OHdG, P < 0.01 versus baseline levels) in both groups. However, the decreases in UAE, serum HMGB1 and serum IL-6 were significantly greater in the telmisartan group than in the enalapril group at 6 months (P < 0.05, P < 0.01 and P < 0.01, respectively) and 12 months (all, P < 0.05). CONCLUSIONS: Telmisartan seems to be equivalent to enalapril in lowering BP, but telmisartan has more potent renoprotective, anti-inflammatory and antioxidative effects than enalapril in patients with hypertensive ADPKD. © Copyright 2012 Southern Society for Clinical Investigation.

Matsumoto S.,Shinmatsudo Central General Hospital | Homma Y.,University of Tokyo
International Journal of Urology | Year: 2015

Objectives: To investigate brain activity related to bladder sensation in interstitial cystitis patients. Methods: A total of 10 interstitial cystitis patients (all women; mean age 68years) and 10 healthy controls (all women; mean age 64years) participated in the present study. Frontal lobe blood flow was measured non-invasively by using multichannel near-infrared spectroscopy with large and small bladder volumes (created by infusing water) up to the first desire to void. Results: The frontal cortex of the right and left hemisphere was activated, and the activation was detected as an increase in oxyhemoglobin concentration. The increase during the first desire to void in the interstitial cystitis group was greater than that in the control group. In addition, this difference was particularly observed in Brodmann's areas 9, 44, 45 and 46, reportedly associated with micturition and sensory modulation. Conclusions: The present study shows that the frontal area is largely activated during bladder filling in interstitial cystitis patients. Our findings suggest that the major change in cerebral blood flow is related to the characteristic urinary symptoms of interstitial cystitis patients. © 2015 The Japanese Urological Association.

Matsumoto S.,Shinmatsudo Central General Hospital | Ishikawa A.,University of Tokyo | Homma Y.,University of Tokyo
Neurourology and Urodynamics | Year: 2011

Aims In order to understand frontal lobe responses in bladder sensation in healthy subjects, we examined the cortical localization of response to the different bladder volumes. Methods Frontal blood flow was measured non-invasively in 24 resting adults using multi-channel near infrared spectroscopy (NIRS). Changes in bladder volume were induced by infusing and releasing water from the bladder. Two states of bladder sensation have been induced, "first desire to void" and "strong desire to void. Results NIRS analysis revealed that cerebral responses to bladder sensation were associated with increased levels of oxy-hemoglobin in the bilateral frontal cortex. The responses became stronger in the state of strong desire to void at enlarged bladder volume (P < 0.01). These results indicate that bilateral frontal areas are involved in bladder perception related to increased urine volumes in adults. Conclusions The dynamic changes in cerebral blood oxygenation were similar to those assessed in other methodologies such as f-MRI and PET. This result suggests that NIRS study might be available for investigating the mutual relationship between bladder and brain in patients suffering from neurological problems and urinary tract symptoms. © 2011 Wiley-Liss, Inc.

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