Yoichi M Ito

Hokkaido University, Sapporo, Hokkaido, Japan

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Publications (62)205.04 Total impact

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    ABSTRACT: Clinical practice enables nursing students to acquire essential professional skills, but little is known about nursing students' perceptions of the clinical learning environment (CLE) in Nepal.
    No preview · Article · Jan 2016
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    ABSTRACT: Background: Amino acids (AAs) are emerging as a new class of effective molecules in the etiology of obesity and diabetes mellitus. However, most investigations have focused on subjects with obesity and/or impaired glucose regulation; the possible involvement of AAs in the initial phase of glucose dysregulation remains poorly understood. Furthermore, little attention has been given to possible associations between the pattern/degree of fat deposition and the plasma AA profile. Our objective was therefore to determine the relationships between plasma AA concentrations and the type/degree of obesity and glucose regulation in Japanese adults with normal glucose tolerance. Methods: Eighty-three subjects with normal glucose tolerance were classified as obese or nonobese and as visceral obesity or nonvisceral obesity. Correlations between the plasma levels of 23 AAs and somatometric measurements, visceral fat area (VFA), subcutaneous fat area (SFA), and 75-g oral glucose tolerance test results were analyzed. Results: Obesity or visceral obesity was associated with higher levels of branched-chain AAs (isoleucine, leucine, and valine), lysine, tryptophan, cystine, and glutamate but lower levels of asparagine, citrulline, glutamine, glycine, and serine (p < 0.04). Age- and gender-adjusted analyses indicated that VFA was positively correlated with tryptophan and glutamate levels, whereas VFA and SFA were negatively correlated with citrulline, glutamine, and glycine levels (p < 0.05). The fasting and 2-h plasma glucose levels or the homeostasis model assessment of insulin resistance were positively correlated with valine, glutamate, and tyrosine levels but negatively correlated with citrulline, glutamine, and glycine levels. The homeostasis model assessment for the β-cell function index was positively correlated with leucine, tryptophan, valine, and glutamate levels but negatively correlated with citrulline, glutamine, glycine, and serine levels (p < 0.05). Conclusions: The present study identified specific associations between 10 AAs and the type/degree of obesity, and indices of glucose/insulin regulation, in Japanese adults with preserved glucose metabolism. With the growing concern about the increasing prevalence of obesity and diabetes, the possible roles of these AAs as early markers and/or precursors warrant further investigation.
    Preview · Article · Jan 2016 · Nutrition & Metabolism
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    ABSTRACT: Objective: To examine the utility and safety of photodynamic diagnosis(PDD) after oral administration of 5-aminolevulinic acid(5-ALA)(ALA-PDD) of non-muscle-invasive bladder cancer(NMIBC) using fluorescent-light(FL)-cystoscopy. Methods: The study was a single-arm, open-label, multi-center prospective study on ALA-PDD of NMIBC, with safety as the primary endpoint and efficacy as the secondary endpoint. Diagnostic potential was evaluated through comparisons with the conventional diagnostic method using a white-light(WL)-source. Clinically recommended doses were also examined. Oral administration of 5-ALA(1.0g/50mL) was performed 180-240min before FL-cystoscopy, and positive or negative results were judged using a WL-source and based on presence or absence of red fluorescence on exposure to a blue FL-source. Results: Regarding safety, the adverse drug reactions were observed as grade 1 pruritus in 1 patient(0.6%). As for efficacy, specificity and positive predictability were lower than those of a WL-source, but sensitivity was higher with a FL-source than with a WL-source. The proportion of patients with tumors detected only by FL-cystoscopy was greater than the proportion of patients with tumors detected only by conventional WL-cystoscopy. Moreover, not only sensitivity, but also the proportion of patients with tumors detected only by FL-cystoscopy, was highest among patients who received 5-ALA at ≧20mg/kg/body. Conclusions: ALA-PDD was shown to be safe and effective. Furthermore, diagnostic accuracy of PDD increased with increased dose of 5-ALA, and the recommended dose was determined as ≧20mg/kg/body in the present study.
    No preview · Article · Jan 2016 · Photodiagnosis and photodynamic therapy
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    ABSTRACT: Background: There is no consensus regarding the number of intraoperative assessments required to reliably measure trainee performance. This study used generalizability theory (GT) to describe factors contributing to score variance and to estimate the number of assessments needed to achieve high standards of reliability. Methods: While performing laparoscopic procedures, trainees were assessed by the attending surgeon using Global Operative Assessment of Laparoscopic Skills (GOALS). Data were collected prospectively (2-month intervals), assessing each trainee multiple times. Reliability coefficient was calculated using trainees, cases, and raters as factors. Results: Eighteen trainees were included for a total of 65 assessments. Total variance in scores was accounted for as follows: 66.1% by trainees, 31.6% by the interaction between trainees and cases, and 2.3% by raters. At least 3 cases are required for reliable scores using GOALS. Conclusions: Trainees accounted for most of the variance in GOALS scores with a minimum of 3 cases required to improve the reliability of the scores obtained. These data may guide the implementation of performance assessments in surgical training programs.
    No preview · Article · Nov 2015 · American journal of surgery
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    ABSTRACT: Background: Comprehensive evaluation of endothelium-dependent and endothelium-independent vascular functions in peripheral arteries and coronary arteries in smokers has never been performed previously. Through the use of brachial artery ultrasound and oxygen-15-labeled water positron emission tomography (PET), we sought to investigate peripheral and coronary vascular dysfunctions in smokers. Methods and results: Eight smokers and 10 healthy individuals underwent brachial artery ultrasound at rest, during reactive hyperemia [250mmHg cuff occlusion (flow-mediated dilatation (FMD)], and following sublingual nitroglycerin (NTG) administration. Myocardial blood flow (MBF) was assessed through O-15-labeled water PET at rest, during adenosine triphosphate (ATP) administration, and during a cold pressor test (CPT). Through ultrasound, smokers were shown to have significantly reduced %FMD compared to controls (6.62±2.28% vs. 11.29±2.75%, p=0.0014). As assessed by O-15-labeled water PET, smokers were shown to have a significantly lower CPT response than were controls (21.1±9.5% vs. 50.9±16.9%, p=0.0004). There was no relationship between %FMD and CPT response (r=0.40, p=0.097). Endothelium-independent vascular dilatation was similar for both groups in terms of coronary flow reserve with PET (p=0.19). Smokers tended to have lower %NTG in the brachial artery (p=0.055). Conclusions: Smokers exhibited impaired coronary endothelial function as well as peripheral brachial artery endothelial function. In addition, there was no correlation between PET and ultrasound measurements, possibly implying that while smokers may have systemic vascular endothelial dysfunction, the characteristics of that dysfunction may be different in peripheral arteries and coronary arteries.
    No preview · Article · Nov 2015 · Journal of Cardiology
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    ABSTRACT: Background: Smoking may have multifactorial effects on asthma phenotypes, particularly in severe asthma. Cluster analysis has been applied to explore novel phenotypes, which are not based on any priori hypotheses. Objective: To explore novel severe asthma phenotypes by cluster analysis when including cigarette smokers. Methods: We recruited a total of 127 subjects with severe asthma, including 59 current or ex-smokers, from our university hospital and its 29 affiliated hospitals/pulmonary clinics. Twelve clinical variables obtained during a two-day hospital stay were used for cluster analysis. After clustering using clinical variables, the sputum levels of 14 molecules were measured to biologically characterize the clinical clusters. Measurements and main results: Five clinical clusters were identified, including 2 characterized by high pack-year exposure to cigarette smoking and low FEV1/FVC. There were marked differences between the two clusters of cigarette smokers; one had high levels of circulating eosinophils, high immunoglobulin E levels, and a high sinus disease score. The other was characterized by low levels of the same parameters. Sputum analysis revealed increased levels of interleukin-5 in the former cluster and increased levels of interleukin-6 and osteopontin in the latter. The other 3 clusters were similar to those previously reported: young onset/atopic, nonsmoker/less eosinophilic, and female/obese. Key clinical variables were confirmed to be stable and consistent one year later. Conclusion: This study reveals 2 distinct phenotypes of severe asthma in current and former cigarette smokers with potentially different biological pathways contributing to fixed airflow limitation. Clinical trial registered with www.umin.ac.jp (000003254).
    Full-text · Article · Sep 2015
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    ABSTRACT: An appropriate biomarker for spinocerebellar degeneration (SCD) has not been identified. Here, we performed gait analysis on patients with pure cerebellar type SCD and assessed whether the obtained data could be used as a neurophysiological biomarker for cerebellar ataxia. We analyzed 25 SCD patients, 25 patients with Parkinson's disease as a disease control, and 25 healthy control individuals. Acceleration signals during 6min of walking and 1min of standing were measured by two sets of triaxial accelerometers that were secured with a fixation vest to the middle of the lower and upper back of each subject. We extracted two gait parameters, the average and the coefficient of variation of motion trajectory amplitude, from each acceleration component. Then, each component was analyzed by correlation with the Scale for the Assessment and Rating of Ataxia (SARA) and the Berg Balance Scale (BBS). Compared with the gait control of healthy subjects and concerning correlation with severity and disease specificity, our results suggest that the average amplitude of medial-lateral (upper back) of straight gait is a physiological biomarker for cerebellar ataxia. Our results suggest that gait analysis is a quantitative and concise evaluation scale for the severity of cerebellar ataxia.
    No preview · Article · Sep 2015 · Journal of the neurological sciences
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    ABSTRACT: Students in clerkship are expected to gain clinical expertise by interacting with real patients in clinical situations. Monitoring and predicting the students' encounter diseases (EDs) is important for providing an optimal experience. EDs should be compared with the available diseases (ADs) at the clerkship site and with the required diseases described in some guidelines for the clinical curriculum. To explore the differences in ADs as learning resources among different types of clerkship sites and to investigate discrepancies between EDs and ADs. A retrospective observational study used secondary data from government statistics to compare ADs of various types of observable clerkship sites by biplot analyses, which allowed multivariate comparisons. EDs collected from logbooks during clerkships at a university hospital were also compared with ADs across sites. The distributions of ADs differed according to institutional type, and EDs at Kyushu University Hospital were similar to the ADs for the category of hospitals in which it was placed. EDs at a clerkship site may be predictable to some extent by analysing the site's distribution of ADs, but further study is needed. Biplot is useful for visualising these types of statistical similarity.
    No preview · Article · Jun 2015 · Medical Teacher
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    ABSTRACT: Background: The aim of the study was to examine the longitudinal change in quality of life components of patients with chronic obstructive pulmonary disease (COPD). Methods: In the Hokkaido COPD Cohort Study, 261 subjects were appropriately treated and followed over 5 years with a 74% follow-up rate at the end. The longitudinal changes in St George's Respiratory Questionnaire (SGRQ) scores were annually evaluated with forced expiratory volume in 1 second (FEV1). The subjects were classified into the rapid decliners, slow decliners, and sustainers based on AFEV1/year. Results: The activity component of SGRQ generally deteriorated over time, and its annual decline was the greatest in the rapid decliners (<25th percentile). In contrast, the symptom component improved significantly year by year in the sustainers (>75 percentile), and it did not deteriorate even in the rapid decliners. Of the baseline data, predictors for worsening of the activity component were older age and lower body mass index. Larger reversibility was related to symptom component improvement. Of the follow-up data, AFEV1/year was the best predictor for worsening of the components of SGRQ. Continuous smoking was another factor for worsening of the activity component. For the symptom component, a history of exacerbation by admission definition was the determinant of its deterioration, whereas use of beta agonists was related to improvement. Conclusion: The longitudinal changes of quality of life and their determinants are markedly different and independent between its components. The activity component of SGRQ generally deteriorated over years, while the symptom component rather improved in some patients with COPD under appropriate treatment.
    No preview · Article · Apr 2015 · International Journal of COPD
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    ABSTRACT: The reliability of CT assessment of regional bronchodilation is not universally accepted. In this study, using our proprietary 3D-CT software, we first examined airway inner luminal area (Ai) before and after inhalation of SFC in a group of COPD patients and then evaluated the same parameters for two sets of CT data obtained from clinically stable subjects with no intervention. We conducted CT at deep inspiration and pulmonary function tests before and one week after inhalation of SFC in 23 COPD patients. As a non-intervention group, we used two sets of CT data obtained with one-year interval in another group of subjects who demonstrated stable pulmonary function (n=8). We measured Ai at the mid-portions of 3rd to 6th generation in 8 bronchi of the right lung, a total of 32 identical sites before and after intervention. The average bronchodilation at all sites (ΔAi%: 28.2±4.1 (SE)%) (r=0.65, p<0.001) and that of each generation significantly correlated with % improvement of FEV1 (ΔFEV1%), which increased from 1.40±0.10L to 1.58±0.10L. When subjects were classified into two groups in terms of mean ΔFEV1%, even the poor responders (ΔFEV1% <14% above baseline, n=13) displayed significantly larger ΔAi% compared with the non-intervention group (19.1±4.6% versus 2.1±3.9%). Inter-observer variability for overall ΔAi% was within acceptable levels. CT can reliably detect the regional bronchodilation in 3rd to 6th generation airways when ΔFEV1 is as small as 180ml on average. This study was registered in the UMIN Clinical Trials Registry (UMIN-CTR) system (http://www.umin.ac.jp/. No. UMIN 000002668). Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    No preview · Article · Mar 2015 · European journal of radiology
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    ABSTRACT: Bar-code technology, used for verification of patients and their medication, could prevent medication errors in clinical practice. Retrospective analysis of electronically stored medical error reports was conducted in a university hospital. The number of reported medication errors of injected drugs, including wrong drug administration and to the wrong patient, was compared before and after implementation of the bar-code verification system for inpatient care. A total of 2867 error reports associated with injection drugs were extracted. Wrong patient errors decreased significantly after implementation of the bar-code verification system (17.4/year vs. 4.5/year, p< 0.05), although wrong drug errors did not decrease sufficiently (24.2/year vs. 20.3/year). The source of medication errors due to wrong drugs was drug preparation in hospital wards. Bar-code medication administration is effective for prevention of wrong patient errors. However, ordinary bar-code verification systems are limited in their ability to prevent incorrect drug preparation in hospital wards.
    No preview · Article · Feb 2015 · Technology and health care: official journal of the European Society for Engineering and Medicine
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    ABSTRACT: Symptoms and signs and indices of right heart function are predictors of clinical outcomes in patients with pulmonary hypertension (PH). However, the significance of right atrial (RA) indices has not been sufficiently investigated. We investigated whether RA parameters predict outcomes in patients with pre-capillary PH. Study subjects were 68 patients with pre-capillary PH. RA size and function (systolic, reservoir, and conduit functions) were evaluated by cardiac magnetic resonance imaging. During the mean follow-up period of 24 months, 16 of 68 patients experienced clinical worsening (CW), defined as hospitalization because of right heart failure, lung transplantation, or PH-related death. Kaplan-Meier and log-rank test showed that World Health Organization functional class, pericardial effusion, increased brain natriuretic peptide concentration, reduced right ventricular ejection fraction (RVEF), increased minimum RA volume index, and decreased RA reservoir volume were associated with CW-free survival. The combination of RVEF and RA reservoir function was a better predictor of CW-free survival. In univariate Cox hazard proportional analysis, CW was associated with the RA reservoir volume index (hazard ratio [HR] = 0.80). In multivariate analysis, CW was associated with World Health Organization functional class (HR = 4.3), RA minimum volume index (HR = 1.07), and RA reservoir volume index (HR = 0.73). RA volume and reservoir function and their combined use with RVEF are novel predictors of CW in patients with pre-capillary PH. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Feb 2015 · The Journal of Heart and Lung Transplantation
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    ABSTRACT: Purpose: The predictive value of FDG PET at thyroid remnant ablation was evaluated in comparison to radioiodine uptake in high-risk patients with differentiated thyroid cancer. Patients and methods: One hundred forty-one patients who underwent radioiodine therapy (RIT) after total thyroidectomy and received at least 1 further RIT due to suspected metastases were retrospectively analyzed. Patients had not received RIT previously. FDG PET was performed before thyroid remnant ablation. Thyroid-stimulating hormone-stimulated serum thyroglobulin (Tg) was measured for biochemical response assessment (change of Tg between the first and second RIT, ΔTg). Results: Biochemical response could be evaluated in 80 patients; survival data could be obtained for 88 patients (maximum, 124 months). Biochemical response was significantly better in patients with radioiodine-positive metastases compared with patients with radioiodine-negative metastases (median ΔTg I+, 55.8% vs I-, 112.6%; P < 0.01). Regarding survival, deaths occurred later in patients with radioiodine-positive metastases compared with radioiodine-negative patients; however, there was no significant difference regarding overall survival (I+, 61.3% vs I-, 58.2%; P > 0.05). Patients with FDG-positive metastases at thyroid remnant ablation showed a poorer biochemical response compared with patients with FDG-negative metastases (median ΔTg FDG+, 77.5% vs FDG-, 53.2%; P < 0.05), and these groups also differed significantly regarding survival (overall survival FDG+, 48.5% vs FDG-, 100%, P < 0.05). Conclusions: At thyroid remnant ablation, FDG PET is more predictive for long-term survival, whereas radioiodine uptake is more important for short-term response. FDG PET performed at thyroid remnant ablation might represent a useful tool for management of high-risk patients with differentiated thyroid cancer.
    No preview · Article · Jan 2015 · Clinical Nuclear Medicine
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    ABSTRACT: This study aims to survey the current practice in Japan for the prevention and treatment of missing data in clinical trials since the publication of regulatory guidelines on missing data issues. A web-based questionnaire was conducted among 65 member companies of the Japan Pharmaceutical Manufacturers Association in 2013. Responses were obtained on 187 clinical trials from 55 companies, including 42 based in Japan and 13 based in other countries. Missing data were most frequent in trials involving the central nervous system (65.2% had ≥10% missing data). Overall, last observation carried forward (LOCF) was the most popular method for handling missing data (45.0%), followed by mixed-effect models for repeated measures (15.5%), although this was used as frequently as LOCF imputation in central nervous system trials. Even after the publication of regulatory guidelines discouraging use of LOCF, LOCF imputation remains the most popular method for treating missing data among pharmaceutical manufacturers in Japan.
    No preview · Article · Oct 2014 · Therapeutic Innovation and Regulatory Science
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    ABSTRACT: Effective treatments for malignant neuroendocrine tumors are under development. While iodine-131 metaiodobenzylguanidine ((131)I-MIBG) radiotherapy has been used in the treatment of malignant neuroendocrine tumors, there are few studies evaluating its therapeutic effects and safety in a multicenter cohort. In the current study, we sought to evaluate the effects and safety of (131)I-MIBG therapy for conditions including malignant pheochromocytoma and paraganglioma within a multicenter cohort. Forty-eight malignant neuroendocrine tumors (37 pheochromocytoma and 11 paraganglioma) from four centers underwent clinical (131)I-MIBG radiotherapy. The tumor responses were observed before and 3 to 6 months after the (131)I-MIBG radiotherapy in accordance with RECIST criteria. We also evaluated the data for any adverse effects. The four centers performed a total of 87 (131)I-MIBG treatments on 48 patients between January 2000 and March 2009. Of the treatments, 65 were evaluable using RECIST criteria. One partial response (PR), 40 stable disease (SD), and 9 progressive disease (PD) in malignant pheochromocytoma were observed after each treatment. Fourteen SD and one PD were observed in paraganglioma. Patients with normal hypertension (systolic blood pressure (BP) > 130 mmHg) showed significantly reduced systolic BP after the initial follow-up (n=10, 138.1±8.2 to 129.5±13.5 mmHg, P=0.03). In adult neuroendocrine tumors with a treatment-basis analysis, there were side effects following 41 treatments (47.1%) and most of them (90.2%) were minor. In this multicenter registry, PR or SD was achieved in 84.6% of the treatment occasions in adult neuroendocrine tumors through (131)I-MIBG radiotherapy. This indicated that most of the (131)I-MIBG radiotherapy was performed safely without significant side effects.
    Preview · Article · Sep 2014 · Endocrine Journal
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    ABSTRACT: To address the role of cancer-stroma interactions, we performed gene expression profiling of both cancer and stroma, using matching samples of endometrial cancer (EC), and analyzed the relationship between the gene expression pattern and prognosis in EC. Sixty EC cases were included in this study (38 nonrecurrent and 22 recurrent). Cancer and stroma were separated by performing laser capture microdissection, and microarray analysis was performed separately on cancer and stromal cells. Genes related with progression-free survival (PFS) in cancer and stroma were analyzed using the Cox regression model, and we established a formula, based on the gene expression pattern of cancer and stroma, to predict recurrence using logistic regression. We estimated the accuracy of the formula using the 0.632 method. All cases were classified based on the 79 selected genes of cancer and stroma related to PFS, based on unsupervised clustering. A total of 143 genes in cancer, and 79 genes in stroma were significantly related with PFS. The estimated area under the curve of receiver operating characteristics curve in cancer and stroma to predict recurrence were 0.800 and 0.758, respectively. Based on the 79 genes of cancer, the 22 recurrent cases were divided into two groups, which generally correlated with the histological grade. In contrast, based on the 79 genes of stroma, the 22 recurrent cases displayed homogeneous gene expression, unrelated to the histological grade. We conclude that gene expression profiles of cancer and stroma can predict the recurrence of EC and stromal that gene expression does not depend on the cancer grade. © 2014 Wiley Periodicals, Inc.
    No preview · Article · Sep 2014 · Genes Chromosomes and Cancer
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    ABSTRACT: Background Colorectal adenoma develops into cancer with the accumulation of genetic and epigenetic changes. We studied the underlying molecular and clinicopathological features to better understand the heterogeneity of colorectal neoplasms (CRNs). Methods We evaluated both genetic (mutations of KRAS, BRAF, TP53, and PIK3CA, and microsatellite instability [MSI]) and epigenetic (methylation status of nine genes or sequences, including the CpG island methylator phenotype [CIMP] markers) alterations in 158 CRNs including 56 polypoid neoplasms (PNs), 25 granular type laterally spreading tumors (LST-Gs), 48 non-granular type LSTs (LST-NGs), 19 depressed neoplasms (DNs) and 10 small flat-elevated neoplasms (S-FNs) on the basis of macroscopic appearance. Results S-FNs showed few molecular changes except SFRP1 methylation. Significant differences in the frequency of KRAS mutations were observed among subtypes (68% for LST-Gs, 36% for PNs, 16% for DNs and 6% for LST-NGs) (P<0.001). By contrast, the frequency of TP53 mutation was higher in DNs than PNs or LST-Gs (32% vs. 5% or 0%, respectively) (P<0.007). We also observed significant differences in the frequency of CIMP between LST-Gs and LST-NGs or PNs (32% vs. 6% or 5%, respectively) (P<0.005). Moreover, the methylation level of LINE-1 was significantly lower in DNs or LST-Gs than in PNs (58.3% or 60.5% vs. 63.2%, P<0.05). PIK3CA mutations were detected only in LSTs. Finally, multivariate analyses showed that macroscopic morphologies were significantly associated with an increased risk of molecular changes (PN or LST-G for KRAS mutation, odds ratio [OR] 9.11; LST-NG or DN for TP53 mutation, OR 5.30; LST-G for PIK3CA mutation, OR 26.53; LST-G or DN for LINE-1 hypomethylation, OR 3.41). Conclusion We demonstrated that CRNs could be classified into five macroscopic subtypes according to clinicopathological and molecular differences, suggesting that different mechanisms are involved in the pathogenesis of colorectal tumorigenesis.
    Preview · Article · Aug 2014 · PLoS ONE
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    ABSTRACT: Objectives 123I-metaiodobenzylguanidine (MIBG) has been used to estimate cardiac sympathetic nervous innervation. Heterogeneous MIBG distribution is mainly associated with high physiological MIBG uptakes in the liver. We postulate that prone position acquisition might be especially effective for MIBG, providing for separation from high liver uptake similar to that provided by perfusion single-photon emission computed tomography (SPECT). We investigated whether prone-position acquisition improved MIBG image quality by comparing our results to those acquired using supine MIBG and high-quality 11C-hydroxyephedrine (HED) positron emission tomography/computed tomography PET/CT. Methods Ten male volunteers (body mass index (BMI) 22.7 ± 3.4) underwent prone and supine MIBG and HED PET. Relative regional tracer uptake was estimated in early MIBG and HED. Acquired images were divided into 17 segments and were grouped into 4 regions: anterior, inferior, septum, and lateral. For each patient, the inferior/anterior ratio was calculated. Results The quality of images acquired using prone MIBG was better than that using supine MIBG (p
    No preview · Article · Jun 2014 · Annals of Nuclear Medicine
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    ABSTRACT: Radiotherapy for high-grade meningioma (HGM) is one of the essential treatment options for disease control. However, appropriate irradiation timing remains under debate. The object of this study is to discern which prognostic factors impact recurrence in HGM patients and to propose a risk-stratification system for the application of postoperative radiotherapy. We retrospectively reviewed 55 adult patients who were diagnosed with Grade II and III intracranial meningioma. Cox regression models were applied to the analysis for impact on early recurrence in HGM patients without postoperative radiotherapy. Grade III malignancy (P = 0.0073) and transformed histology (P = 0.047) proved to be significantly poor prognostic factors of early recurrence by multivariate analysis. The other candidates for recurrence factors were Simpson Grade 3-5 resection, preoperative Karnofsky Performance status < = 70%, and MIB-1 labeling index > = 15%. According to these prognostic factors, postoperative HGM patients could be stratified into three recurrence-risk groups. The prognoses were significantly different between each group, as the 3-year actual recurrence-free rates were 90% in low-risk group, 31% in intermediate-risk group, and 15% in high-risk group. We propose recurrence-risk stratification for postoperative HGM patients using clinically available factors. Our results suggest that the prognosis for patients with high-risk HGMs is dismal, whereas HGM patients belonging to the low-risk group could have favorable prognoses. This stratification provides us with the criteria necessary to determine whether to apply adjuvant radiotherapy to postoperative HGM patients, and to also help identify potentially curable HGMs without adjuvant radiotherapy.
    Full-text · Article · May 2014 · PLoS ONE
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    ABSTRACT: Long-acting β2-agonists and leukotriene receptor antagonists are two principal agents that can be added to inhaled corticosteroids (ICS) for patients with asthma that is not adequately controlled by ICS alone. The Gly16Arg genotype of the β2-adrenergic receptor (ADRB2) gene may influence the bronchodilator effects of β2-agonists. We hypothesized that differential responses to long-acting β2-agonists or leukotriene receptor antagonists might be determined partly by the Gly16Arg polymorphism in Japanese asthma patients. This randomized, genotype-stratified, two-period crossover study included 80 patients with mild-to-moderate asthma (35 Arg/Arg and 45 Gly/Gly individuals). The primary study outcome was the difference in peak expiratory flow (ΔPEF) (ΔPEF, l/min) by genotype after 16 weeks of treatment with salmeterol (ΔPEFsal) or montelukast (ΔPEFmon). In addition, multivariate analyses were used to identify independent factors that were predictive of responses to each treatment. The mean ΔPEFsal-ΔPEFmon was 19.3±46.6 among Arg/Arg individuals and 16.8±51.5 among Gly/Gly individuals, indicating that the Gly16Arg genotype did not influence the differential bronchodilator effect of the two agents. Multivariate analysis showed that higher peripheral eosinophil counts were associated with better response to salmeterol (P<0.05). The Gly16Arg genotype did not influence the differential bronchodilator effect of salmeterol or montelukast as an add-on therapy to ICS within 16 weeks of follow-up. Higher peripheral eosinophil counts may be associated with better responses to salmeterol in combination with ICS.
    No preview · Article · Mar 2014 · Pharmacogenetics and Genomics