Aoki S.,Tokyo Women's Medical University |
Takei Y.,Kitasato Institute Hospital |
Suzuki K.,Tokyo Women's Medical University |
Masukawa A.,Tokyo Women's Medical University |
Arai Y.,Tokyo Women's Medical University
Auris Nasus Larynx | Year: 2012
Objective: Recent development of 3-dimensional analysis of eye movement enabled to detect the eye rotation axis, which is used to determine the responsible semicircular canal(s) in dizzy patients. Therefore, the knowledge of anatomical orientation of bilateral semicircular canals is essential, as all 6 canals influence the eye movements. Subjects and methods: Employing the new head coordinate system suitable for MR imaging, we calculated the angles of semicircular canal planes of both ears in 11 dizzy patients who had normal caloric response in both ears. Results: The angles between adjacent canal pairs were nearly perpendicular in both ears. The angle between the posterior canal planes and head sagittal plane was 51° and significantly larger the angle between the anterior canal planes and head sagittal plane, which was 35°. The angle between the horizontal canal plane and head sagittal plane was almost orthogonal. Pairs of contralateral synergistic canal planes were not parallel, forming 10° between right and left horizontal canal planes, 17° between right anterior and left posterior canal planes and 19° between the right posterior and left anterior canal planes. Conclusion: Our measurement of the angles of adjacent canal pairs and the angle between each semicircular canal and head sagittal plane coincided with those of previous reports obtained from CT images and skull specimens. However, the angles between contralateral synergistic canal planes were more parallel than those of previous reports. © 2011 Elsevier Ireland Ltd.
Suzuki Y.,Toho University |
Motoya S.,Sapporo Kosei General Hospital |
Hanai H.,Hamamatsu South Hospital |
Matsumoto T.,Hyogo College of Medicine |
And 8 more authors.
Journal of Gastroenterology | Year: 2014
Background: Adalimumab is a fully human, monoclonal antibody against tumor necrosis factor that is approved in Western countries for the treatment of moderately to severely active ulcerative colitis (UC). Methods: This 52-week, phase 2/3, randomized, double-blind study evaluated adalimumab for induction and maintenance treatment in 273 anti-TNF-naive Japanese patients with UC who were refractory to corticosteroids, immunomodulators, or both. Patients received placebo, adalimumab 80/40 (80 mg at week 0, then 40 mg every other week), or adalimumab 160/80 (160/80 mg at weeks 0/2, then 40 mg every other week) in addition to background UC therapy. Results: At week 8, remission rates were similar among treatment arms, but more patients treated with adalimumab 160/80 achieved response (placebo, 35 %; 80/40, 43 %; 160/80, 50 %; P = 0.044 for 160/80 vs placebo) and mucosal healing (placebo, 30 %; 80/40, 39 %; 160/80, 44 %; P = 0.045 for 160/80 vs placebo) compared with placebo. At week 52, more patients receiving adalimumab 40 mg every other week achieved response (18 vs 31 %; P = 0.021), remission (7 vs 23 %; P = 0.001), and mucosal healing (16 vs 29 %; P = 0.015) compared with placebo. Week 8 response to adalimumab was associated with greater rates of response (61 %), remission (46 %), and mucosal healing (57 %) at week 52 relative to the overall population. Rates of serious adverse events were similar between treatment arms. Conclusions: Induction with adalimumab 160/80 mg led to early response and mucosal healing. Maintenance adalimumab had greater rates of long-term response, remission, and mucosal healing compared with placebo. No new safety signals were identified. © 2013 The Author(s).
Nishiguchi S.,Hyogo College of Medicine |
Sakai Y.,Hyogo College of Medicine |
Kuboki M.,Liver Disease Treatment Center |
Tsunematsu S.,Kitasato Institute Hospital |
And 6 more authors.
Liver International | Year: 2014
Abstract: Background & Aims: Faldaprevir (BI 201335) is a potent once-daily (QD) NS3/4A protease inhibitor for the treatment of patients with genotype-1 (GT-1) hepatitis C virus (HCV). The aim of this study was to evaluate the safety, pharmacokinetics and efficacy of faldaprevir plus pegylated interferon alfa-2a (PegIFN) and ribavirin (RBV) in Japanese patients infected with chronic GT-1 HCV. Methods: Part 1 of this phase II study was a randomized, double-blind, placebo-controlled, dose-ascending study. Treatment-naïve patients received faldaprevir 120 or 240 mg QD, or placebo, plus PegIFN/RBV for 4 weeks, then PegIFN/RBV alone for 44 weeks. In Part 2 (open label), treatment-experienced patients received faldaprevir 240 mg QD plus PegIFN/RBV for 4 weeks, then PegIFN/RBV alone for 44 weeks. Efficacy was assessed using sustained virological response (SVR) 24 weeks after treatment completion. The pharmacokinetics, safety and tolerability of faldaprevir were also assessed. Results: SVR was achieved by 4/6 (67%) treatment-naïve patients treated with faldaprevir 120 mg QD, 5/6 (83%) patients treated with faldaprevir 240 mg QD and 2/4 (50%) patients who received placebo. Of the treatment-experienced patients, 3/6 (50%) achieved SVR. Faldaprevir was well tolerated. There was one serious adverse event, which was not considered to be treatment related. Rash and hyperbilirubinaemia were more frequently reported with faldaprevir than with placebo in treatment-naïve patients, but no cases were severe or serious and none led to discontinuation. Steady-state plasma concentrations of faldaprevir were reached within 7 days of QD dosing. Conclusions: Faldaprevir with PegIFN/RBV was efficacious and well tolerated, supporting further evaluation of this combination in Japanese patients. © 2013 John Wiley & Sons A/S.
Koyama T.,Tachikawa Hospital |
Niikura H.,Ota Memorial Hospital |
Shibata M.,Tachikawa Hospital |
Moritani K.,Tachikawa Hospital |
And 4 more authors.
IJC Metabolic and Endocrine | Year: 2014
Background: Excessive early inflammation after myocardial infarction (MI) is associated with poor outcomes. However, an approach for suppressing this early inflammation has not been reported. We previously reported that postconditioning with lactate-enriched blood (PCLeB) induced excellent microcirculation recovery in patients with acute MI. We therefore tested the hypothesis that early inflammation after MI could be suppressed by PCLeB. Methods and results: We treated 17 consecutive patients with ST-elevation MI using primary percutaneous intervention with our modified postconditioning protocol within 12. h of onset. In this protocol, the duration of each brief reperfusion was prolonged from 10 to 60. s in a stepwise manner. Lactated Ringer's solution (20-30. mL) was injected directly into the culprit coronary artery at the end of each brief reperfusion, and the balloon was quickly inflated at the site of the lesion to trap lactate within the ischemic myocardium. Each brief ischemic period lasted 60. s. After 7. cycles of balloon inflation and deflation, full reperfusion was performed; subsequently, stenting was performed. C-reactive protein (CRP) levels were measured daily and the peak values within the first 7. days post-admission were recorded. Peak CRP values were compared with those in matched control patients with acute MI treated without postconditioning. In both groups, only patients with CRP values <. 0.3. mg/dL on admission were included. Peak CRP values were significantly lower in the postconditioned group (control group vs. postconditioned group, 5.05. ±. 4.85 vs. 1.66. ±. 1.57. mg/dL; p. <. 0.01). Conclusion: PCLeB may suppress early inflammation after MI. © 2014 The Authors.
Hirai K.,International Goodwill Hospital |
Hirai K.,Yokohama City University |
Takano Y.,Kitasato Institute Hospital |
Uchio E.,Fukuoka |
Kadonosono K.,Yokohama City University
Clinical Ophthalmology | Year: 2012
Purpose: To evaluate the therapeutic effects of atelocollagen absorbable punctal plugs. Method: Seventy-four eyes in 37 patients with dry eye disease (DED) underwent punctal plug occlusion using atelocollagen plugs and were followed up for 24 weeks. Subjective symptoms were evaluated using the ocular surface disease index (OSDI) questionnaire. Ocular surface disease parameters, including the Schirmer test, phenol red thread test, tear break-up time(TBUT), and fluorescein and Rose Bengal staining, were recorded before and 1, 4, 8, 16, and 24 weeks after treatment. Results: In comparison with the pretreatment data, the subjective symptoms and ocular surface disease parameters showed significant improvement after atelocollagen punctal occlusion. The average time of relapse was 17.4 ±5.1 weeks. No severe complications occurred, and none of the plugs had to be removed because of local discomfort or epiphora. Conclusion: Atelocollagen absorbable punctal plugs effectively improved ocular surface disorders in DED. These plugs are a safe and effective alternative in the treatment of DED. © 2012 Hirai et al, publisher and licensee Dove Medical Press Ltd.
Kodama K.,Stanford University |
Kodama K.,Lucile Packard Childrens Hospital |
Tojjar D.,Lund University |
Yamada S.,Kitasato Institute Hospital |
And 5 more authors.
Diabetes Care | Year: 2013
OBJECTIVE - Human blood glucose levels have likely evolved toward their current point of stability over hundreds of thousands of years. The robust population stability of this trait is called canalization. It has been represented by a hyperbolic function of two variables: insulin sensitivity and insulin response. Environmental changes due to global migration may have pushed some human subpopulations to different points of stability. We hypothesized that there may be ethnic differences in the optimal states in the relationship between insulin sensitivity and insulin response. RESEARCH DESIGN AND METHODS - We identified studies that measured the insulin sensitivity index (S I) and acute insulin response to glucose (AIRg) in three major ethnic groups: Africans, Caucasians, and East Asians.We identified 74 study cohorts comprising 3,813 individuals (19 African cohorts, 31 Caucasian, and 24 East Asian).We calculated the hyperbolic relationship using the mean values of SI and AIRg in the healthy cohorts with normal glucose tolerance. RESULTS - We found that Caucasian subpopulations were located around themiddle point of the hyperbola, while African and East Asian subpopulations are located around unstable extreme points, where a small change in one variable is associated with a large nonlinear change in the other variable. CONCLUSIONS - Our findings suggest that the genetic background of Africans and East Asians makes them more and differentially susceptible to diabetes than Caucasians. This ethnic stratification could be implicated in the different natural courses of diabetes onset. © 2013 by the American Diabetes Association.
Yamada S.,Kitasato Institute Hospital
Current Vascular Pharmacology | Year: 2011
Metabolic syndrome comprises of a cluster of several risk factors including abdominal obesity, dyslipidemia, elevated blood pressure, and insulin resistance. Many manifestations occur in sequence which is also referred to as the metabolic domino. Because the renin-angiotensin system (RAS) seems to be involved in this domino effect, RAS blockade by angiotensin II receptor blockers (ARB) offers a therapeutic tool for treating hypertension and ultimately the metabolic syndrome itself. In this paper, I describe the effects of ARBs on adiponectin, blood pressure, and fatty liver. Several clinical studies have reported that ARBs elevate adiponectin. ARBs that activate the PPARγ may be more effective than others. In terms of blood pressure, transient ARB administration may prevent the development of hypertension and high doses of ARB may regress mild hypertension. In terms of fatty liver, several research studies have indicated that ARBs may prevent triglyceride accumulation in liver. Again, ARBs that activate PPARγ may be more effective than others. Thus, PPARγ-activating ARBs offer the most hopeful treatment for metabolic syndrome. Further studies are needed to confirm this hypothesis. © 2011 Bentham Science Publishers Ltd.
Suzuki K.,Kitasato Institute Hospital |
Aiura K.,Kawasaki City Hospital |
Matsuda S.,Keio University |
Itano O.,Keio University |
And 3 more authors.
Clinical and Experimental Metastasis | Year: 2013
Activation of nuclear factor-κB (NF-κB) has been implicated in metastasis of pancreatic cancer. We investigated the effects of the novel NF-κB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) on the inhibition of liver metastasis of pancreatic cancer in a mouse model of clinical liver metastasis. Nude mice were xenografted by intra-portal-vein injection with the human pancreatic adenocarcinomas cell line AsPC-1 via small laparotomy. Mice were treated with DHMEQ and gemcitabine (GEM), alone or in combination. The combination of GEM + DHMEQ showed a stronger antitumor effect than either monotherapy. Apoptosis induction in the metastatic foci was greatest in the DHMEQ + GEM group. Significant reductions in the numbers of neovessels were also seen in the DHMEQ and/or GEM groups. Cell growth inhibition assays revealed no synergistic effect of combination therapy, although each monotherapy had an individual cytotoxic effect. Combination therapy produced the greatest inhibition of tumor cell invasiveness in chemoinvasion assay. In addition, combination therapy significantly down-regulated the expression level of matrix metalloproteinase (MMP)-9 mRNA in AsPC-1 cells. DHMEQ also markedly down-regulated interleukin-8 and MMP-9, while GEM caused moderate down-regulation of vascular endothelial growth factor in metastatic foci, demonstrated by quantitative reverse transcription-polymerase chain reaction. These results demonstrate that DHMEQ can exert anti-tumor effects by inhibiting angiogenesis and tumor cell invasion, and by inducing apoptosis. Combination therapy with DHMEQ and GEM also showed potential efficacy. DHMEQ is a promising drug for the treatment of advanced pancreatic cancer. © 2012 Springer Science+Business Media Dordrecht.
Suzuki S.,Kitasato Institute Hospital
Nihon Hoshasen Gijutsu Gakkai zasshi | Year: 2011
Measurement of T(2) and T(1)ρ relaxation time is a quantitative evaluation technique that uses magnetic resonance imaging. This study aimed to evaluate T(2) and T(1)ρ relaxation time considering the load on the knee. 14 healthy volunteers were studied at 3 T. Four main compartments were defined for cartilage analysis in the knee joint: lateral femoral condyle (LFC), medial femoral condyle (MFC), and lateral and medial tibia (LT and MT). Femur cartilage was partitioned into anterior, middle, and posterior nonweight-bearing (a-NWB, m-NWB, p-NWB) portions and weight-bearing (WB) portions. T(2) and T(1)ρ values between the medial side and lateral side indicated a nonsignificant difference. T(2) and T(1)ρ values of NWB portions were higher than those of WB portions. The measured value rate of extension of NWB to WB was more remarkable in the T(1)ρ value than in the T(2) value. Therefore, evaluating cartilaginous injuries and damages using the T(1)ρ value seems to more effectively describe them.
Shinoda K.,Teikyo University |
Imamura Y.,Teikyo University |
Matsumoto C.S.,Teikyo University |
Mizota A.,Teikyo University |
Ando Y.,Kitasato Institute Hospital
Graefe's Archive for Clinical and Experimental Ophthalmology | Year: 2012
Purpose We report the changes of the retinal pigment epithelium (RPE) determined by optical coherence tomography in a patient with atypical Vogt-Koyanagi-Harada (VKH) disease during the recovery phase. Method Case presentation. Results A 74-year-old woman presented with a central scotoma associated with disc hyperemia, serous retinal detachment, and scleral thickening in her left eye, and was diagnosed with VKH. OCT showed a serous retinal detachment and a wavy RPE contour that corresponded to the choroidal folds. The OCT images clearly showed the dynamic changes of the retina, RPE, and choroid during the recovery phase. Conclusions The OCT was found to be more sensitive in detecting the choroidal folds than angiography. OCT images are valuable not only in the diagnosis, but also for monitoring the morphology of the retina and choroid during the course of VKH. © Springer-Verlag 2012.