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Background: Narcolepsy (NA) is a sleep disorder characterized by excessive daytime sleepiness and an increased propensity of rapid eye movement sleep. If left untreated, NA can lead to academic underachievement or job loss because of dozing off or mistakes caused by inattentiveness due to sleepiness. Purpose: Although untreated narcolepsy patients may suffer from many social disadvantages due to excessive daytime sleepiness, mostly it takes a long time to receive a definitive diagnosis of the disorder. This retrospective study investigated factors related to the period until definitive diagnosis among patients with narcolepsy in Japan. Methods: We enrolled 181 consecutive patients (108 men, 73 women; mean age 37.6 ± 16.6 years old; narcolepsy with cataplexy/narcolepsy without cataplexy = 131:50). Multivariate logistic regression analysis was performed with period until definitive diagnosis as the dependent variable and descriptive clinical variables as the independent variables. Results: The mean period until receiving the diagnosis among the participants was 9.9 ± 10.1 years. More than half of the patients first learned about the disorder from information provided by the media. Multivariate logistic analysis indicated that adult onset ( p < 0.01), onset in 1995 or later ( p < 0.001), and first learning about the disorder from a sleep disorder specialist physician or a general practitioner ( p < 0.001) were associated with a time taken for receiving a definitive diagnosis less than or equal to the median value (7 years). Conclusion: Improving access to information about the concept of the disorder and the medical institutions specialized in sleep disorders, especially via the Internet, would be necessary to promote early diagnosis of the disorder. [ABSTRACT FROM AUTHOR]

Purpose: Although a few prospective studies have addressed the question as to which biomarker of infection in adult patients with febrile neutropenia (FN) is superior, procalcitonin (PCT) or C-reactive protein (CRP), the results have been inconsistent and inconclusive. This was possibly due to the poor sensitivity of previous PCT tests that have a functional sensitivity of 0.5 ng/ml. Methods: Between November 2010 and February 2012, we prospectively compared the diagnostic utility of serum high-sensitivity (hs) PCT (lower limit of detection, 0.02 ng/ml) and CRP levels for detecting bacterial infection in patients with FN. Serum was collected within 72 h after the onset of FN in patients with hematological disorders. Results: Seventy-five febrile episodes were evaluable. The areas under the receiver operating characteristic curves for life-threatening infection defined as septic shock and bacteremia caused by non-coagulase negative staphylococcus were 0.824 (95 % CI 0.711-0.937; P = 0.001) for hsPCT and 0.673 (0.505-0.842; P = 0.068) for CRP, respectively. In contrast, CRP, but not hsPCT, tended to increase significantly with the clinical severity, as indicated by the diagnostic classification ( P = 0.002 for trend). Conclusions: The serum hsPCT test may be more useful than the serum CRP test in the detection of life-threatening infection at an early phase after the onset of FN. In contrast, the serum CRP test may be more useful in diagnosing the severity of infection. However, neither of these tests was able to differentiate the cause of FN with a low probability of fatal outcome. [ABSTRACT FROM AUTHOR]

Summary: This study assessed the effects of physical activity on a 10-year incidence of self-reported vertebral fractures in adult women of a large Japanese cohort. Medium levels of strenuous activity and long-duration sedentary activity were associated with a lower incidence of vertebral fractures; association patterns appear to be different from hip fractures. Introduction: Physical activity helps prevent hip fracture, but little is known about the longitudinal association between physical activity and vertebral fractures. The purpose of this study was to evaluate the effects of physical activity on the 10-year incidence of symptomatic vertebral fractures using data from the Japan Public Health Center-based Prospective Study. Methods: Baseline studies were conducted in 1993-1994, and the follow-up study was conducted 10 years later. We analyzed 23,757 women aged 40-69 years. At baseline, physical activity was assessed as a predictor by using a questionnaire. Subjects were asked to report vertebral fractures that occurred during the 10-year follow-up period. Relative risks (RRs) adjusted for confounders were estimated by multiple logistic regression analysis. Results: The 10-year cumulative incidence of vertebral fractures was 0.67 %. Those who engaged in strenuous physical activity of <1 h/day had a significantly lower incidence of vertebral fractures than those who did not engage in such activity (RR = 0.52, 95 % CI 0.28-0.97), while those engaged in such activity ≥1 h/day did not (RR = 0.82, 95 % CI 0.58-1.14). Long-duration sedentary activity was associated with a low incidence of vertebral fractures ( P for trend = 0.0002), but the frequencies of sports activities and metabolic equivalents were not ( P for trend = 0.0729 and 0.4341, respectively). Conclusions: Strenuous activity and sedentary activity are associated with the incidence of vertebral fractures, although the association may not be linear. The pattern of association between physical activity and vertebral fractures appears to be different from that of hip fractures. [ABSTRACT FROM AUTHOR]

Study design:Cross-sectional study.Objectives:There are ethnic differences in the distribution of abdominal obesity associated with metabolic disorders. In Japan, the appropriate reference values for abdominal obesity have not been established in individuals with spinal cord injury (SCI), although there are a number of studies in Western countries. This study evaluates the associations between visceral fat area (VFA), waist circumference (WC) and body mass index (BMI), to examine cutoffs and estimate the error for WC and BMI equivalent to 100 cm2 VFA in Japanese men with SCI.Setting:National Rehabilitation Center for Persons with Disabilities, Japan.Methods:Seventy-four men (aged 45.6 (s.d. 14.3) years) participated in the study. VFA was quantified using computed tomography at the level of the umbilicus, and associations were determined using nonlinear regression analysis. The error of the estimates from the regression equation was assessed using a Bland-Altman plot.Results:The mean VFA was 101.2 (s.d. 53.0) cm2 and 32 subjects had a VFA ⩾100 cm2. The cutoffs for a VFA of 100 cm2 were WC, 81.3 cm and BMI, 22.5 kg m−2. The relationship between the estimated and actual values showed that the error increased as VFA increased, which resulted in a negative proportional bias.Conclusion:The suggested cutoff for Japanese men with SCI is a VFA of 100 cm2, which is lower than that in the healthy able-bodied population for both WC and BMI. Further investigation is needed to determine the reference value for estimating SCI-specific VF accumulation. [ABSTRACT FROM AUTHOR]

Background: Residual risk of cardiovascular disease from increased small dense low-density lipoprotein (sdLDL)-cholesterol levels and low n-3 polyunsaturated fatty acid (PUFA) levels is a considerable therapeutic issue. The purpose of this study was to evaluate the effect of ezetimibe as an add-on to statins and supplemental eicosapentaenoic acid (EPA) on sdLDL cholesterol and absorption of EPA in patients with coronary artery disease. Methods: The study population consisted of ten male patients who were concurrently receiving statins and EPA 1,800 mg/day. Serum lipids and PUFAs, including EPA and arachidonic acid, were measured in blood samples collected before ezetimibe (baseline), 4 weeks after starting 10-mg/day ezetimibe, and 4 weeks after discontinuing ezetimibe. Results: Ezetimibe significantly decreased sdLDL-cholesterol levels after 4 weeks of treatment (baseline 35 ± 13 mg/dl; treatment 27 ± 9 mg/dl), but the levels returned to baseline after discontinuation of ezetimibe (37 ± 13 mg/dl). The concentration of EPA did not significantly change during the study. Conclusion: Ezetimibe shows great promise as an add-on therapy to statins to reduce sdLDL-cholesterol-related residual risk of cardiovascular disease without affecting absorption of supplemental EPA in patients with coronary artery disease. [ABSTRACT FROM AUTHOR]

Background: Perceived stress and coping strategies may influence the risk of cardiovascular disease through their possible association with inflammation, but data remain controversial for perceived stress or scanty for coping strategies. Purpose: We examined the associations of perceived stress and coping strategies with serum high-sensitivity C-reactive protein (CRP) in a Japanese general population. Methods: This cross-sectional study included 2,971 men and 4,902 women aged 40-69 years who were enrolled between 2005 and 2007. Subjects with possible inflammation-related disease, CRP levels ≥3,000 ng/mL, or currently used analgesics or lipid-lowering drugs were excluded. Analyses were performed by gender with adjustment for lifestyle, socioeconomic, and psychosocial factors. Results: Unexpectedly, elevated perceived stress was significantly associated with lower CRP levels in men ( P < 0.001) but not in women ( P = 0.90) after adjustment for age and covariates. Among five items of coping strategies evaluated, 'disengagement' showed a significant inverse association with CRP in men only ( P = 0.027). In addition, a possible interaction between 'emotional support seeking' and perceived stress on CRP was detected in men ( P = 0.021); 'emotional support seeking' was associated with lower CRP at the high stress level only ( P = 0.028). Conclusions: Both perceived stress and coping strategies may be associated with systemic inflammation in Japanese men, yet caution must be exercised before accepting the stress-inflammation-disease pathway. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to assess the brain core temperature of patients with mild traumatic brain injury (mTBI) using a noninvasive temperature measurement technique based on the diffusion coefficient of the cerebrospinal fluid. Methods: This retrospective study used the data collected from April 2008 to June 2011. The patient group comprised 20 patients with a Glasgow Coma Scale score of 14 or 15 who underwent magnetic resonance imaging within 30 days after head trauma. The normal control group comprised 14 subjects who volunteered for a brain checkup (known in Japan as 'brain dock'). We compared lateral ventricular (LV) temperature between patient and control groups. Follow-up studies were performed for four patients. Results: LV temperature measurements were successfully performed for both patients and controls. Mean (±standard deviation) measured LV temperature was 36.9 ± 1.5 °C in patients, 38.7 ± 1.8 °C in follow-ups, and 37.9 ± 1.2 °C in controls, showing a significant difference between patients and controls ( P = 0.017). However, no significant difference was evident between patients and follow-ups ( P = 0.595) or between follow-ups and controls ( P = 0.465). Conclusions: A reduction in brain core temperature was observed in patients with mTBI, possibly due to a global decrease in metabolism. [ABSTRACT FROM AUTHOR]

Purpose We aimed to investigate the recommended dose for the combination of TSU-68, a multiple-receptor tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2 and platelet-derived growth factor receptor-β, and S-1, an oral fluoropyrimidine, in patients with advanced hepatocellular carcinoma (HCC) based on its associated dose-limiting toxicity (DLT) frequency. We also determined the safety, tolerability, pharmacokinetics (PK), and efficacy of the combination treatment. Patients and methods Patients without any prior systemic therapy received 400 mg/day TSU-68 orally and 80 mg/day (level 1) or 100 mg/day (level 2) S-1 for 4 or 2 weeks followed by a 2- or 1-week rest period (groups A and B, respectively). According to the treatment, patients progressed from level 1B to level 2A, then level 2B. Safety and response rates were assessed. Results Eighteen patients were enrolled. Two patients at levels 1B and 2A but none at level 2B showed DLTs. The common adverse drug reactions were a decrease in hemoglobin levels, hypoalbuminemia, and anorexia, which were mild in severity (grades 1-2). PK data from levels 1B and 2A indicated that the area under the curve for TSU-68 and 5-fluorouracil was unlikely to be affected by the combination treatment. Response rate, disease control rate, median time to progression, and median overall survival were 27.8 %, 61.1 %, 5.3 months, and 12.8 months, respectively. Conclusion The recommended dose for advanced HCC should be 400 mg/day TSU-68 and 100 mg/day S-1 for 4 weeks followed by 2-week rest. [ABSTRACT FROM AUTHOR]

Summary: This multi-center, prospective, open-label, observational study evaluated the effects of once-monthly minodronate (50 mg) on treatment persistence, bone turnover markers, bone mineral density, low back pain, and upper gastrointestinal symptoms in outpatients with osteoporosis previously treated with daily or weekly bisphosphonate products. Introduction: The purposes of this study were to investigate the effects of once-monthly oral minodronate (MIN 50 mg) on bone turnover markers and bone mineral density, low back pain, and upper gastrointestinal symptoms, as well as preference for and treatment persistence of MIN 50 mg among Japanese osteoporosis patients currently treated with daily or weekly bisphosphonates. Methods: Study patients were allocated based on their preference to either the Switch group (patients willing to switch over to MIN 50 mg) or the Continue group (patients wanting to continue their current therapies). Patients' treatment persistence and satisfaction levels with the therapies were assessed using a self-administered questionnaire. The study endpoints were serum TRACP-5b, serum P1NP, bone mineral density, upper gastrointestinal symptoms, and low back pain. Results: In total, 264 and 133 patients were allocated into the Switch and Continue groups, respectively. Approximately, 65 % of patients were willing to switch to MIN 50 mg, with the predominant reason being 'less frequent dosing more convenient.' Treatment persistence was significantly higher in the Switch group (MIN 50 mg) than the Continue group. Almost all patients with abnormal bone metabolism markers demonstrated normalization after switchover. MIN 50 mg alleviated low back pain and upper gastrointestinal symptoms induced by prior bisphosphonate use. Conclusions: MIN 50 mg alleviates low back pain, reduces bone turnover markers and increases bone density, and induces fewer upper gastrointestinal symptoms after switchover from prior bisphosphonate products, and therefore, it may provide patients with a more convenient treatment option and enhance long-term treatment persistence. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to assess computed tomography (CT) and magnetic resonance (MR) imaging findings of salivary gland tumors of the parotid gland with emphasis on intratumoral cystic components. Methods: Seventy-two histopathologically confirmed salivary gland tumors of the parotid gland (44 benign and 28 malignant), which underwent both CT and MR imaging including contrast-enhanced study, were included in this study. We retrospectively reviewed images for the presence, number, occupying rate, margin characteristics, distribution, and predominant MR signal intensity of intratumoral cystic components. Results: The prevalence of cystic components was greater in malignant than benign tumors (79 vs. 50 %, p < 0.05). The number and occupying rate were similar between benign and malignant tumors. The irregular margins were more frequent in malignant than benign tumors (73 vs. 27 %, p < 0.01). The frequency of eccentric location was greater in benign than malignant tumors (91 vs. 55 %, p < 0.01), whereas the frequency of centric location was greater in malignant than benign tumors (32 vs. 0 %, p < 0.01). On T1-weighted images, the frequency of hyperintensity was greater in benign than malignant tumors (50 vs. 9 %, p < 0.01), whereas that of isointensity was greater in malignant than benign tumors (50 vs. 0 %, p < 0.01). Multiple logistic regression analysis showed that the absence of irregular margins of cystic components only was significantly correlated with the presence of benign salivary gland tumors ( p < 0.01). Conclusion: Imaging features of intratumoral cystic components may help to differentiate benign from malignant tumors of the parotid salivary gland. [ABSTRACT FROM AUTHOR]

The article discusses a study which describes the ethnic differences in toxicity during early phase clinical trials for oncology drugs. The researchers have evaluated the Phase I clinical trials for new drug applications and approved doses in Japan and other Western countries. The findings indicate that differences in toxicity for oncology drugs are associated with ethnic differences.

Purpose: Faster eating is positively associated with body mass index in apparently healthy Japanese populations. In the present study, we examined the associations between self-reported rate of eating and visceral and subcutaneous fat areas in apparently healthy middle-aged Japanese men. Methods: We conducted a cross-sectional study of men who participated in health checkups in Japan. We removed participants who were diagnosed with metabolic diseases by the time of their health checkups. A total of 320 subjects aged 30-64 years (mean ± standard deviation, 47.4 ± 8.6 years) were selected. We compared the associations between rate of eating and various clinical parameters including visceral and subcutaneous fat areas, using analysis of covariance (ANCOVA), which was adjusted by age and lifestyle factors such as alcohol intake, energy intake, smoking, and physical activity. Multivariate logistic regression analyses (MLRA) were performed with visceral fat area (cm) as the dependent variable and independent variables that included self-reported rate of eating. Results: Tukey's multiple test following ANCOVA showed that self-reported rate of eating was positively associated with visceral fat area (cm), but not with subcutaneous fat area (cm). MLRA showed that the odds ratio of rate of eating for visceral fat area in tertile (T) 3 (>100 cm) compared with T1 (≤70 cm) was 1.99 (95 % CI 1.40-2.90, P < 0.01), and the association remained after adjustment for the subcutaneous fat area. Conclusions: The present results show that self-reported faster eating is positively associated with visceral fat accumulation, independently of subcutaneous fat accumulation, in apparently healthy Japanese men. [ABSTRACT FROM AUTHOR]

Study design:Nonrandomized study.Objectives:The purpose of this study was to determine the effects of long and intensive exercise on interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in athletes with cervical spinal cord injuries (CSCI).Setting:The 30th Oita International Wheelchair Marathon Race.Methods:Blood samples from six athletes with CSCI and eight athletes with thoracic and lumber spinal cord injuries (SCI) participating in wheelchair half marathon race were collected before the race, immediately after the race and 2 h after the race. IL-6, TNF-α, adrenaline and blood cell counts were measured.Results:Monocyte count remained stable throughout the study in the CSCI group but was significantly high at 2 h after the race in the SCI group. Plasma IL-6 concentrations were significantly elevated immediately after the race in both groups, although the levels in CSCI were significantly lower than in the SCI group. Plasma adrenaline was significantly elevated immediately after the race in the SCI group but recovered at 2 h after the race. In contrast, plasma adrenaline did not change in the CSCI group throughout the study and was significantly lower than in the SCI group. Plasma TNF-α did not change throughout the study in the SCI group compared with a significant decrease at 2 h after the race in the CSCI group.Conclusion:Long and intensive exercise increased IL-6 in the CSCI group despite the small muscle mass and lack of sympathetic nervous system. The post-race fall in plasma TNF-α in the CSCI group could be related to the inhibitory effect of rising IL-6 in the presence of normal monocyte count and stable adrenaline level. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to examine the possible effects of healthcare resource factors, socioeconomic factors, and sociodemographic factors on variations in hospitalization expenditures of elderly patients in Japan at different levels of urbanization. Subject and methods: A secondary analysis was conducted using data obtained from a regional health care cost report and the Portal Site of Official Statistics of Japan. The regional unit of analysis used was the secondary medical care area. We divided these areas into three groups based on their levels of urbanization (low, middle, and high urbanization), indicated by their respective population densities of inhabitable areas. Multiple linear regression models were used to analyze the candidate factors affecting per capita hospitalization expenditures of elderly residents. Results: The significance and magnitude of associations were observed to vary according to different levels of urbanization. Our findings showed that medical resource factors and sociodemographic factors were more influential in areas of low urbanization, whereas the number of hospital beds and socioeconomic factors appeared more influential in high urbanization areas. Conclusion: Policies designed to contain healthcare expenditures should take regional characteristics and levels of urbanization into account in order to support the development and implementation of region-specific improvements that ensure affordable healthcare for the elderly. [ABSTRACT FROM AUTHOR]

Objective:This study aimed to examine whether, on the basis of the relationship between sensors attached on the upper limbs and energy expenditure (EE) at the time of wheelchair propulsion, there are differences in the measurement of EE depending on the sensor attachment site and whether addition of the angular velocity information to the acceleration value is advantageous. We also aimed to clarify the variables used to estimate EE as well as the estimated error.Setting:Laboratory of the National Hospital Organization Murayama Medical Center, Japan.Methods:Six male subjects with spinal cord injuries participated in the study. Each wore sensors at the wrist and the middle upper arm on both sides while driving a wheelchair on a treadmill at three levels: very, very light; very light; and fairly light. Triaxial acceleration, triaxial angular velocity and EE were measured during driving. We analyzed the correlation between EE and acceleration, angular velocity and synthesized values of acceleration and angular velocity at each location using regression, multiple regression and Bland-Altman analyses.Results:The determination coefficients between EE and the acceleration, angular velocity and synthesized values of acceleration and angular velocity varied from 0.68 to 0.87 at each location. The mean difference between the measured and estimated EE varied from 0.0028 (s.d., 0.0027) kcal min−1 kg−1 on the right upper arm.Conclusion:These findings suggest that combining the synthesized values of angular velocity and acceleration of the motion sensors on the upper limbs might reflect EE during a wheelchair driving activity on a treadmill. [ABSTRACT FROM AUTHOR]

The article provides calculation and characterization of the safety indices of approved drugs in Japan to systematically explore factors that affect the safety index. Topics covered include an analysis of drugs classified as new molecular entities that were approved in Japan, the lack of significant positive correlation between the no observed-adverse effect level (NOAEL) and phase 1 indices and the qualitative measure to interpret the phase 1 index against the NOAEL index.

Background: High residual platelet reactivity in patients receiving clopidogrel is associated with an increased risk of a cardiovascular event after coronary stenting. The aim of our study was to evaluate the impact of the cytochrome P450 (CYP) 3A5 and CYP2C19 polymorphisms on platelet reactivity during dual antiplatelet therapy. Methods: We determined the CYP2C19 and CYP3A5 genotypes of 101 angina patients (65 male patients, mean age 64 years) receiving dual antiplatelet therapy with aspirin and clopidogrel and evaluated the effect of these polymorphism on platelet reactivity at the early and late phases of treatment using a conventional light transmission aggregometry. Early and late phases were defined as 24 h after the loading dose and after 9 months on a maintenance dose of 75 mg daily, respectively. Results: The distribution of the CYP2C19 genotype was 30 % in extensive metabolizers (EM; CYP2C19*1/*1), 46 % in intermediate metabolizers (IM; *1/*2, *1/*3), and 25 % in poor metabolizers (PM; *2/*2, *2/*3, *3/*3). Platelet reactivity levels in during the early and late phases were 3,793 ± 1,476 and 2,960 ± 1,410, respectively, in EM, 4,706 ± 1,417 and 3,239 ± 1,479, respectively, in IM, and 5,402 ± 776 and 4,736 ± 1,356 aggregation units (AU)•min, respectively in EM. The distribution of the CYP3A5 genotype was 33 % in patients carrying the wild-type or one loss-of-function allele (Expressor phenotype; *1/*1 and *1/*3, respectively) and 67 % in those carrying two loss-of-function alleles (Non-expressor; *3/*3). In total, eight patients were EM+Expressor, 22 were EM+Non-expressor, 18 were IM+Expressor, 28 were IM+Non-expressor, eight were PM+Expressor, and 17 were PM+Non-expressor. In the late phase of PM with the CYP2C19 polymorphism, the levels of platelet reactivity according to CYP3A5 genotype were 3,963 ± 1,436 and 5,100 ± 1,190 AU•min in Expressor and Non-expressor, respectively ( P < 0.05), however, there was no difference in platelet reactivity between Expressor and Non-expressor in EM and IM. Conclusions: Our results suggest that antiplatelet response to clopidogrel in the late phase depends on the CYP3A5 polymorphism in PM with CYP2C19. [ABSTRACT FROM AUTHOR]

Summary: This study examined the accuracy of thoracic and lumbar kyphotic angles as well as anthropometric indicators for discriminating patients with vertebral fracture among Japanese women >50 years old with back pain. Along with region-specific kyphotic angles and anthropometric indicators, the combination of thoracic and lumbar kyphotic angles offered the highest accuracy. Introduction: Vertebral fractures have been associated with thoracic kyphosis. However, reports on lumbar kyphotic changes in association with vertebral fracture are scarce. This study investigated the accuracy of thoracic kyphotic angle (TKA) and lumbar kyphotic angle (LKA) measurements as well as anthropometric indicators (wall-occiput distance (WOD) and rib-pelvis distance (RPD)) in discriminating patients with vertebral fracture. Methods: Lateral radiographs of the spine were obtained in 70 postmenopausal Japanese women who visited an orthopedic clinic with low back pain (mean age, 76.2 ± 9.0 years). Radiographic vertebral fracture was diagnosed using quantitative measurement according to Japanese criteria. Osteoarthritis (OA) was defined as Kellgren-Lawrence (KL) grade 3 or higher. TKA and LKA were measured using SpinalMouse®. WOD and RPD were also measured. Results: At least one vertebral fracture was present in 49 subjects (70 %). Women with vertebral fractures showed significant increases in LKA, TKA + LKA, and WOD and decreases in RPD. Logistic regression analysis showed significant association between TKA + LKA and vertebral fracture independent of the presence of OA. Receiver operating characteristic analysis revealed that TKA was useful for discriminating thoracic fractures (area under the curve (AUC), 0.730) and LKA was useful for lumbar fractures (AUC, 0.691). The combination of TKA + LKA offered the highest accuracy for detecting thoracic, lumbar, and any vertebral fractures, with AUCs of 0.779, 0.728, and 0.783, respectively. WOD and RPD showed low-to-moderate accuracies for thoracic, lumbar, and any vertebral fractures. Conclusions: Assessment of spinal kyphosis by SpinalMouse® as well as anthropometric indicators proved useful in discriminating subjects with vertebral fractures. These convenient and radiation-free methods could contribute to early diagnosis of vertebral fractures and subsequent appropriate treatment, thus preventing additional osteoporotic fractures. [ABSTRACT FROM AUTHOR]

Objectives:The purpose of this study was to clarify the prognostic factors for cervical spondylotic amyotrophy (CSA).Methods:The authors retrospectively reviewed the medical records of 47 consecutive patients with CSA in whom the presence/absence of the pyramidal tract sign was noted. We analyzed whether the age, sex, presence of diabetes mellitus, medication (vitamin B12), type of the most atrophic and impaired muscle, the muscle strength at the presentation, the presence of the pyramidal tract sign, magnetic resonance imaging (MRI) findings, including the presence and number of T2 high signal intensity areas (T2 HIA) in the spinal cord and the conversion to surgery were associated with the recovery of muscle strength in the patients. In addition, we also investigated whether the duration of symptoms before surgery and the type of surgery were associated with the recovery of muscle strength in patients who required conversion to surgical treatment.Results:The presence of T2 HIA on MRI (P=0.002), the number of T2 HIA on MRI (P=0.002) and conversion to surgery (P=0.015) were found to be significantly associated with a poorer recovery at the observational final follow-up. Further, the presence of the pyramidal tract sign (P=0.043) was significantly associated with a poor recovery at the final follow-up after surgery.Conclusion:The presence of a high signal intensity change on T2-weighted MRI and the pyramidal tract sign can be used as prognostic factors for patients with CSA. [ABSTRACT FROM AUTHOR]

Study design:Cross-sectional study.Objective:To identify the physical impairments and walking function required for community ambulation in patients with cervical incomplete spinal cord injury (ISCI).Setting:Chubu Rosai Hospital, Nagoya, Japan.Methods:Forty patients with cervical ISCI (mean age: 49.9 years, American Spinal Injury Association Impairment Scale D) were included. The primary outcome measure was community ambulation based on Spinal Cord Independence Measure outdoor scores for a distance of >480 m. We measured the upper- and lower-extremity motor scores (UEMS and LEMS), sensory and spasticity. The walking tests included 10 m of walking at a comfortable- and maximum-walking speed (CWS and MWS; m s−1), 6 min walking test (6MWT; m) and the walking index for spinal cord injury II (WISCI II). Multivariate logistic regression models were used to assess the physical impairments associated with community ambulation. Receiver operating characteristic curves were analyzed to determine the cutoff points for physical impairment and walking function.Result:The LEMS (beta coefficient (β)=0.71) and UEMS (β=0.41) were independently associated with community ambulation in patients with cervical ISCI. The cutoff points of the LEMS, UEMS, CWS, MWS, 6MWT and WISCI II were 41.5, 36.5, 1.00 m s−1, 1.32 m s−1, 472.5 m and 17.5, respectively, which suggests moderate to high accuracy.Conclusion:The LEMS and UEMS were the most important factors affecting community ambulation in patients with cervical ISCI. The cutoff points of the walking function tests were highly accurate; therefore, these points can serve as targets for walking training in the future. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to assess the association between the cortical shape of the mandible, as detected on panoramic radiographs, and trabecular bone structure, as assessed by cone-beam computed tomography (CBCT), in Japanese adults. Methods: Panoramic radiographs and CBCT images of the mandibles of 50 subjects (18 men, 32 women), aged 45-86 years, were evaluated. An experienced oral and maxillofacial radiologist categorized the cortical shape of the mandible as detected on panoramic radiographs as normal, mildly to moderately eroded, and severely eroded cortices, respectively. All mandibles were scanned using CBCT. Four bone structure parameters of the basal portion of the mandible were calculated in three dimensions using an image-analysis system: total bone volume (mm); cortical bone volume fraction (%); trabecular bone volume fraction (%); fractal dimension. One-way analysis of covariance with Bonferroni correction was employed to evaluate differences in the four bone parameters among the three cortical shape groups. Pearson's correlation coefficient was calculated to examine correlations between age and cortical and trabecular bone volume fractions. Results: Progression of cortical bone erosion was significantly associated with increased trabecular bone volume fraction ( P < 0.001) and increased fractal dimension ( P = 0.01). Cortical bone volume fraction decreased significantly with age ( P = 0.04). However, trabecular bone volume fraction tended to increase with age ( P = 0.06). Conclusions: The change in the trabecular bone structure of the mandible may differ from that of the general skeleton in Japanese adults. [ABSTRACT FROM AUTHOR]

Purpose: The aim was to investigate both individual and synergistic effects of quercetin-3- O-β-glucoside (Q3G) and fructooligosaccharide (FOS) on indices of metabolic syndrome and plasma total cholesterol level with potential mechanisms of action. Methods: Five groups of rats were fed a dextrin-based diet as the normal reference group, or sucrose-based (S) diets with 0.3 % Q3G, 5 % FOS, or 0.3 % Q3G + 5 % FOS (Q3G + FOS) for 48 days. Oral glucose tolerance tests (OGTTs) were conducted on days 0, 14, 28, and 45, and adipose tissue and aortic blood were collected on day 48. Effects of Q3G and FOS on portal GLP-1 secretion were separately examined using rats after ileal administration. Results: Abdominal fat weight reduced in FOS-fed groups. Blood glucose levels of the Q3G + FOS group at 60 min in OGTT and HOMA-IR (0.25 ± 0.03 vs 0.83 ± 0.12 on day 45) were clearly lower in the Q3G + FOS group than in S group throughout the experimental period. Muscle Akt phosphorylation was enhanced only in the Q3G group. The plasma quercetin was largely increased by FOS feeding on day 48 (18.37 ± 1.20 with FOS, 2.02 ± 0.30 without FOS). Plasma total cholesterol levels in the Q3G + FOS group (3.10 ± 0.12, P < 0.05 on day 45) were clearly suppressed compared to the S group (4.03 ± 0.18). GLP-1 secretion was enhanced in Q3G + FOS group than in Q3G or FOS group. Conclusion: Q3G + FOS diet improved glucose tolerance, insulin sensitivity, and total cholesterol level with increasing GLP-1 secretion and a higher level of blood quercetin. Q3G + FOS may reduce the risk of T2DM. [ABSTRACT FROM AUTHOR]

Purpose: The effect of an AA deficiency on catecholamine biosynthesis in adult mice in vivo is unknown. Therefore, we quantified catecholamine and the expression of catecholamine synthetic enzymes in the adrenal glands of senescence marker protein-30 (SMP30)/gluconolactonase (GNL) knockout (KO) mice placed in an AA-deficient state. Methods: At 30 days of age, mice were divided into the following 4 groups: AA (−) SMP30/GNL KO, AA (+) SMP30/GNL KO, AA (−) wild type (WT), and AA (+) WT. The AA (+) groups were given water containing 1.5 g/L AA, whereas the AA (−) groups received water without AA until the experiment ended. In addition, all mice were fed an AA-depleted diet. Catecholamine levels were measured by a liquid chromatographic method. Tyrosine hydroxylase, dopa decarboxylase, dopamine β-hydroxylase, and phenylethanolamine N-methyltransferase mRNA expression levels were measured with the quantitative real-time polymerase chain reaction (qPCR). Tyrosine hydroxylase and dopamine β-hydroxylase protein levels were quantified by Western blot analysis. Results: In the adrenals of AA (−) SMP30/GNL KO mice, noradrenaline and adrenaline levels decreased significantly compared to other three groups of mice, although there were no significant differences in dopamine β-hydroxylase or phenylethanolamine N-methyltransferase mRNA content. Moreover, there was no significant difference in their dopamine β-hydroxylase protein levels. On the other hand, AA depletion did not affect dopamine levels in adrenal glands of mice. Conclusion: An AA deficiency decreases the noradrenaline and adrenaline levels in adrenal glands of mice in vivo. [ABSTRACT FROM AUTHOR]

Summary: We used quantitative computed tomography and finite element analysis to classify women with and without hip fracture. Highly accurate classifications were achieved indicating the potential for these methods to be used for subject-specific assessment of fracture risk. Introduction: Areal bone mineral density (aBMD) is the current clinical diagnostic standard for assessing fracture risk; however, many fractures occur in people not defined as osteoporotic by aBMD. Finite element (FE) analysis based on quantitative computed tomography (QCT) images takes into account both bone material and structural properties to provide subject-specific estimates of bone strength. Thus, our objective was to determine if FE estimates of bone strength could classify women with and without hip fracture. Methods: Twenty women with femoral neck fracture and 15 women with trochanteric fractures along with 35 age-matched controls were scanned with QCT at the hip. Since it is unknown how a specific subject will fall, FE analysis was used to estimate bone stiffness and bone failure load under loading configurations with femoral neck internal rotation angles ranging from −30° to 45° with 15° intervals. Support vector machine (SVM) models and a tenfold cross-validation scheme were used to classify the subjects with and without fracture. Results: High accuracy was achieved when using only FE analysis for classifying the women with and without fracture both when the fracture types were pooled (82.9 %) and when analyzed separately by femoral neck fracture (87.5 %) and trochanteric fracture (80.0 %). The accuracy was further increased when FE analysis was combined with volumetric BMD (pooled fractures accuracy, 91.4 %) Conclusions: While larger prospective studies are needed, these results demonstrate that FE analysis using multiple loading configurations together with SVM models can accurately classify individuals with previous hip fracture. [ABSTRACT FROM AUTHOR]

Summary: A 3-year follow-up study on 334 young Japanese females enrolled in a university at the age of 18 years revealed that discontinuation of leisure time impact-loading exercises performed in junior high and/or high school was associated with increased risk of reduction in calcaneus osteo-sono assessment index (OSI). Introduction: Bone strength rapidly increases during puberty and reaches its peak by the end of adolescence. The aim of this study was to determine the lifestyle factors that influence the maintenance of calcaneus OSI in young adult females around the time when peak bone mass is attained. Methods: Annual health checkups including OSI measurements, anthropometrics, lifestyle analysis, and blood examination were performed 4 times on 334 Japanese females enrolled in a university at the age of 18 years. According to the slope of OSI change during the 3-year follow-up, the subjects were grouped into two categories: OSI loss (the lowest tertile) and OSI gain/stable (the second and third tertiles). Results: At the baseline assessment, the OSI loss group had higher OSI and height and an earlier menarche age than the OSI gain/stable group. Performing leisure time impact-loading exercise in junior high and/or high school but discontinuing it at university was associated with increased risk of OSI loss, independent of OSI, height and weight at the age of 18 years, weight change during follow-up, age of menarche, energy-adjusted nutrient intake, and alcohol drinking; the odds ratios were 4.1-4.9 compared with those performing impact-loading exercise at university. In particular, duration, frequency, and subjective intensity of impact-loading exercise during high school were positively associated with OSI loss. Conclusion: Discontinuation of leisure time impact-loading exercises performed during late adolescence is associated with an increased risk of OSI loss in young adult females during the 3-year follow-up period. [ABSTRACT FROM AUTHOR]

Few studies in Japan have examined whether children's later mental health is influenced by the way parental authority is exercised, specifically with a focus on gender. Our main purposes of this study were to confirm the three-factor structure of the Japanese version of the Parental Authority Questionnaire (PAQ) and to verify its reliability and validity. We then used structural equation modeling to examine whether children's later mental health was influenced by parents' authoritative, permissive, and authoritarian parenting. The subcategories included in the Japanese version of the Clinical Outcomes in Routine Evaluation-Outcome Measure were chosen as mental health indices. A total of 1,320 people in Japan, including company employees, university students, and hospital staff members, were asked to recall and evaluate the parenting they received and to report on their current mental health. Confirmatory factor analyses verified the three-factor structure of the Japanese version of the PAQ, with a reduction in the number of items from the original version. The respondents, regardless of gender, evaluated their mothers as having been more authoritative than their fathers. Concerning the impact of parenting styles on respondents' later mental health, both maternal and paternal authoritarian parenting styles worsened respondents' later mental health, including symptomatic problems, risk to self and others, life functioning, and psychological well-being. Both maternal and paternal authoritative parenting had a beneficial impact on respondents' later mental health. Simultaneous analyses of multi-groups demonstrated that the nature of these influences did not vary with respondent gender. We present the above results in detail, and discuss them from psycho-socio-cultural viewpoints. [ABSTRACT FROM AUTHOR]

To determine whether the Modified Checklist for Autism in Toddlers (M-CHAT) in conjunction with the routine 18-month health check-up identifies Japanese toddlers with autism spectrum disorder (ASD). Two-stage screening using the M-CHAT was conducted with 1,851 children attending the check-up. Final ASD diagnosis was confirmed at age ≥3 years. Screening identified 20/51 children with ASD: 12/20 true positives were developmentally delayed, whereas 16/22 false negatives were high-functioning. Sensitivity was 0.476, specificity 0.986, positive predictive value 0.455, and likelihood ratio 33.4 for children with ASD. With a few modifications, M-CHAT screening successfully detected toddlers with ASD with and without developmental delay and is a promising screening tool to complement existing community surveillance. [ABSTRACT FROM AUTHOR]

Study design:Retrospective chart review.Objective:To evaluate the clinical outcomes and factors influencing patient satisfaction with Malone antegrade continence enema (MACE) in patients with spina bifida.Setting:Japan.Methods:We performed retrospective analysis of 21 patients with spina bifida who underwent surgical creation of an MACE stoma. Clinical outcomes were evaluated by medical records, operative notes and mailed questionnaires. Patient satisfaction scores (SSs) were measured on a modified visual analog scale (VAS) from 1 to 10, and the factors influencing the SS were analyzed.Results:A 100% return rate for the mailed questionnaires was achieved. All patients underwent in situ appendicocecostomy with cecal plication. There was only one complication that required surgical revision. Regarding fecal continence, the overall success rate was 90%. Although 4 patients (19%) had severe irrigation pain and 4 patients (19%) found the washout time intolerably long, 18 (85%) of them were satisfied with the MACE procedure. Age at operation, experience of retrograde colonic enema (RCE), experience of stomal leakage, increased comfort at school or workplace and increased comfort at sleepovers significantly influenced SSs.Conclusion:MACE is a valuable option in achieving fecal continence in patients with spina bifida, with most patients being satisfied with the procedure. In our analysis, younger age at operation, previous experience of RCE, no stomal leakage and improvement of quality of life (enhanced comfort at school, workplace and sleepovers) significantly influenced the high satisfaction after MACE. [ABSTRACT FROM AUTHOR]

Study Design:This was a retrospective observational study.Objectives:The objectives were to describe the prognosis of upper extremity function following cervical spinal cord injury (CSCI), and to identify prognostic factors for functional recovery.Setting:Spinal Injuries Center, Japan.Methods:Sixty patients with C3-4 CSCI without major bone injury participated in the study. Patients were treated nonsurgically and evaluated using the American Spinal Injury Association (ASIA) scales for the upper and lower extremities, their residual cervical motor functions, the modified Frankel grade and an upper extremity function scale. We compared the findings for the upper extremity function scale at 6 months with those for the residual cervical motor functions and modified Frankel grade obtained 3 days after injury.Results:Most patients with CSCI who could flex their hip and knee from a supine position (95%) or who showed some active elbow extension (86%) 3 days after their injury could use a spoon at 6 months. We compared patients who used their fingers at 6 months to those who could not, and observed significant differences in age and ASIA scores for the upper and lower extremities obtained 3 days after injury. A strong correlation was observed between the initial motor scores and the extent of functional recovery at 6 months.Conclusion:Hip and knee flexion from the supine position and elbow extension 3 days after injury significantly predicted a positive prognosis for upper extremity function. Younger age and higher ASIA motor scores obtained 3 days after injury were factors associated with neurological recovery. [ABSTRACT FROM AUTHOR]

Background: Persistent postoperative supraventricular tachyarrhythmias (SVTs) increase cardiac burden and aggravate cardiac hemodynamics. Therefore, for patients in unstable conditions after surgery, prompt and sustained control of heart rate is essential. The importance of β-adrenoceptor antagonists (β-blockers) in controlling such postoperative atrial fibrillation or atrial flutter has been established, and the usefulness of ultra-short-acting β-blockers with high β selectivity has been suggested based on their safety and efficacy under such circumstances. Objectives: Our objectives were to evaluate the effectiveness and safety of landiolol hydrochloride, an ultra-short-acting β-selective blocker, in the treatment of postoperative SVT in patients with a high risk of myocardial ischemia, or in patients after highly invasive surgery, in a multicenter, randomized, double-blind, placebo-controlled, group-comparative study. Methods: A total of 165 patients were randomly allocated to three groups and received LM or MH doses of landiolol hydrochloride or placebo. LM group: dose L (1-min loading dose at a rate of 0.03 mg/kg/min, followed by a 10-min infusion at 0.01 mg/kg/min) followed by dose M (1-min loading at a rate of 0.06 mg/kg/min, followed by a 10-min infusion at 0.02 mg/kg/min); MH group: dose M followed by dose H (1-min loading dose at a rate of 0.125 mg/kg/min, followed by a 10-min infusion at 0.04 mg/kg/min); placebo (PP) group: dose P (1-min loading dose at a rate of 0 mg/kg/min, followed by a 10-min infusion at 0 mg/kg/min) followed by another round of dose P. If the targeted heart-rate reduction was not obtained at the end of the first 10-min infusion, the higher dose was started. The primary endpoint was the percentage of patients who met the heart-rate reduction criteria (≥20 % reduction and <100 beats/min). The safety endpoint was the incidence of adverse events in each of the three groups. Results: The percentages of patients who met the heart-rate reduction criteria (≥20 % reduction and <100 beats/min) were 0.0, 60.4, and 42.0 % in the PP, LM, and MH groups, respectively. There were significant differences in the LM and MH groups relative to the PP group, but there was no significant difference between the LM and MH groups. No significant difference was observed in the incidence of adverse events among the three groups: 29.6 % in the PP group, 45.5 % in the LM group, and 43.1 % in the MH group. Conclusion: Landiolol hydrochloride is effective and safe for patients with postoperative SVT. [ABSTRACT FROM AUTHOR]

Although it has been suggested that obesity is 'contagious' within the social network, direct cause of this spread of obesity remains unclear. This study hypothesized that Body Image (BI), the perception of one's own body size, may play a role in this obesity spread, since a high prevalence of obesity could shift people's perception of 'what is normal'. Young Japanese females (n = 53) were interviewed within 1 month after moving to New York City, where the prevalence of obesity is substantially higher than that of their home country, Japan. Each participant was examined for her BI in terms of current body size (CBS) and ideal body size (IBS). They were interviewed again 2 months after the first examination. Between the two interviews, the participants' CBS was decreased (having thinner self-image), while the IBS increased (having fatter ideal-image), leading to less dissatisfaction (smaller CBS-IBS) with their body size. These results suggest that one's BI could change in a period as short as 2 months, possibly because of being surrounded by more obese people. The IBS change was positively associated with BMI change (increased by 0.4 ± 0.6 kg/m²), warranting further study on the role of BI in the spread of obesity. [ABSTRACT FROM AUTHOR]

Study design:A cross-sectional analysis.Objective:To examine whether intramedullary stress is related to the appearance of symptoms in cervical spondylotic myelopathy (CSM).Setting:Japan.Methods:Thirty-three consecutive patients with CSM and 30 consecutive patients without CSM were enrolled. A total of 99 disc levels from C3 to C6 in 33 patients with CSM were divided into two groups: 33 disc levels with high signal intensity (HSI) on T2-weighted magnetic resonance image (HSI group) and 66 disc levels without HSI (Non-HSI group). Ninety disc levels from C3 to C6 in patients without CSM were set up in a control group. Intramedullary stress value at each level was analyzed using the finite element method. Stress was compared among the three groups. A cutoff value of stress to present HSI was investigated from receiver operator characteristics (ROC) curve.Results:In all the patients with CSM, the disc level with HSI presented the highest stress among the three disc levels evaluated. The stress was 3.16±0.86 kPa (mean±s.d.) in the HSI group, 1.81±0.72 kPa in the Non-HSI group and 1.01±0.37 kPa in the control group. The stress differed significantly among the three groups (P<0.0001). The qualified cutoff value derived from the ROC curve was 2.30 kPa (sensitivity 78.8%, specificity 91.9%). None of the disc levels in the control group exceeded 2.30 kPa.Conclusion:HSI was strongly associated with intramedullary stress. Threshold of intramedullary stress to present HSI that related closely to the symptoms of myelopathy was revealed. [ABSTRACT FROM AUTHOR]

Purpose: The pharmacokinetics of orally administered immediate-release, twice-daily (BID) and modified-release, once-daily (QD) formulations of tacrolimus have high interindividual variability. We investigated factors affecting interindividual variability of tacrolimus bioavailability in renal transplant patients. Methods: Ninety-seven Japanese renal transplant patients (47 patients on tacrolimus BID and 50 patients on tacrolimus QD) were enrolled in this study. The tacrolimus absolute bioavailability was calculated using the area under the concentration-time curve from 0 to 24 h (AUC) after continuous intravenous infusion and oral formulations of tacrolimus in the same recipient. Results: The median (quartile 1-quartile 3) tacrolimus relative bioavailability for recipients with the CYP3A5*1 or CYP3A5*3/*3 alleles was significantly lower for the tacrolimus QD group [9.1 % (6.3-10.7 %) and 15.4 % (11.5-18.7 %), respectively] than for the tacrolimus BID group [12.6 % (9.9-14.2 %) and 19.3 % (16.5-24.8 %), respectively] ( P = 0.004 and 0.028, respectively). Consequently, tacrolimus absolute bioavailability was lowest for recipients with the CYP3A5*1 allele taking tacrolimus QD. The CYP3A5 polymorphism had no impact on the dose-adjusted AUC of tacrolimus in patients on continuous intravenous infusion ( P = 0.906). Conclusion: The larger interindividual variability of tacrolimus bioavailability for oral formulations appears to be due to the effects of the CYP3A5 polymorphism and the tacrolimus oral formulation. These factors should therefore be taken into account when determining individualized tacrolimus dosing. [ABSTRACT FROM AUTHOR]

We applied an American medical necessity scale, Level of Care Utilization System for Psychiatric and Addiction Services (LOCUS), to psychiatric practice in Japan. This is an exploratory analysis of empirical data of 272 patients. We examined the relationships between levels of care of LOCUS and clinical variables, contribution of care levels on admission decision, and changes in care levels over time. Inpatients showed significantly higher levels of care than outpatients. Levels of care showed significant strong inverse correlations to Global Assessment Scale (GAS) scores, and significant moderate correlations to admission types, care environment, and diagnostic subgroups in almost all groups. Levels of care contributed as much to the admission decision as GAS scores. Levels of care significantly decreased from the time of admission to discharge. Our preliminary evidence indicates that LOCUS is valid and sensitive to change, and applicable for clinical use in Japan. [ABSTRACT FROM AUTHOR]

Purpose: Omeprazole has ( R)- and ( S)-enantiomers, which exhibit different pharmacokinetics (PK) among patients with cytochrome P450 (CYP) 2C19 genotype groups. The aim of this study was to investigate whether the 1-point, 4-h postdose ( R)-omeprazole hydroxylation index (HI) of racemic omeprazole reflects the three CYP2C19 genotype groups in Japanese individuals. Methods: Ninety healthy Japanese individuals were enrolled and classified into the three different CYP2C19 genotype groups: homozygous extensive metabolizers (hmEMs; n = 34), heterozygous EMs (htEMs; n = 44), and poor metabolizers (PMs; n = 12). Blood samples were drawn 4 h after the intake of an oral dose of omeprazole 40 mg, and plasma levels of omeprazole and its metabolites were analyzed by high-performance liquid chromatography (HPLC) using a chiral column. Results: Mean plasma concentrations of ( R)- and ( S)-omeprazole in PMs were significantly higher than those in hmEMs and htEMs, and similar results were obtained in the case of omeprazole sulfone. Additionally, there was a significant difference in plasma concentrations of ( R)-5-hydroxyomeprazole among CYP2C19 genotype groups, whereas no significant differences were observed in that of ( S)-5-hydroxyomeprazole. Similarly, ( R)-omeprazole HI in hmEMs, htEMs, and PMs were 5.6, 3.1, and 0.3, respectively, which were significantly different, but no significant difference was present in the ( S)-omeprazole HI. Conclusion: Our findings demonstrate that ( R)-omeprazole HI correlated better with CYP2C19 genotype groups than racemic-omeprazole HI, and these results may be useful for classification among patients in CYP2C19 genotype groups prior to omeprazole treatment. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the interactions of itraconazole (ITCZ) with orally administered calcineurin inhibitors (CNIs) in Japanese allogeneic hematopoietic stem cell transplant (HSCT) recipients. Methods: Sixteen HSCT patients (8 patients each receiving tacrolimus or cyclosporine) were enrolled. An ITCZ oral solution was administered from day 30 after the initiation of ITCZ administration as a loading dose. Before the co-administration of ITCZ and CNI and 1 week daily thereafter, whole blood ITCZ and CNI (tacrolimus or cyclosporine) concentrations were measured in samples taken just before (C) and 2 h (C) after CNI administration. Results: The median dose-adjusted C values of tacrolimus and cyclosporine on day 7 after the start of ITCZ co-administration were 5.6- and 2.7-fold higher, respectively, than the corresponding values obtained before the initiation of ITCZ treatment. On day 7 after ITCZ treatment, the mean single dosages of tacrolimus and cyclosporine were reduced to 33.7 and 66.5 % of the dosages before ITCZ co-administration, respectively, to adjust the CNI target concentration. Although ITCZ co-administration did not alter the dose-adjusted C values of tacrolimus in a patient with a CYP3A5*1/*1 allele, it did change this value of tacrolimus in patients with CYP3A5*3 alleles. However, in patients receiving cyclosporine, no such tendency was observed. Conclusion: The magnitude of the interaction between orally administered tacrolimus and ITCZ was significantly greater than that between cyclosporine and ITCZ. Prospective analysis of the CYP3A5 polymorphism may be important to ensure safe and reliable immunosuppressive therapy with tacrolimus in patients treated with ITCZ. [ABSTRACT FROM AUTHOR]

The objective was to examine the association between lifestyle and risk for diabetes. For an average of 9.9 years, this study prospectively followed a cohort of 7,211 (2,524 men and 4,687 women) community residents aged 30-69 years without diabetes at a health check-up conducted between April 1990 and March 1992 until diabetes was confirmed or until the end of 2006. The subjects were divided into 6 groups according to their total scores of Breslow's lifestyle index (1-2, 3, 4, 5, 6 and 7 points). The association between lifestyle and diabetes incidence was investigated using Cox proportional hazards regression models. The results showed that the multivariate-adjusted hazard ratios were 0.45 in subjects who scored 5 points, 0.39 in subjects who scored 6 points, and 0.31 in subjects who scored 7 points, compared with subjects who scored 1-2 points. These data indicate that the healthy behaviors prevent the incidence of diabetes. [ABSTRACT FROM AUTHOR]

Objective: This study is a pharmacogenetic clinical trial designed to clarify whether the N-acetyltransferase 2 gene ( NAT2) genotype-guided dosing of isoniazid improves the tolerability and efficacy of the 6-month four-drug standard regimen for newly diagnosed pulmonary tuberculosis. Methods: In a multicenter, parallel, randomized, and controlled trial with a PROBE design, patients were assigned to either conventional standard treatment (STD-treatment: approx. 5 mg/kg of isoniazid for all) or NAT2 genotype-guided treatment (PGx-treatment: approx. 7.5 mg/kg for patients homozygous for NAT2*4: rapid acetylators; 5 mg/kg, patients heterozygous for NAT2*4: intermediate acetylators; 2.5 mg/kg, patients without NAT2*4: slow acetylators). The primary outcome included incidences of 1) isoniazid-related liver injury (INH-DILI) during the first 8 weeks of therapy, and 2) early treatment failure as indicated by a persistent positive culture or no improvement in chest radiographs at the8th week. Results: One hundred and seventy-two Japanese patients (slow acetylators, 9.3 %; rapid acetylators, 53.5 %) were enrolled in this trial. In the intention-to-treat (ITT) analysis, INH-DILI occurred in 78 % of the slow acetylators in the STD-treatment, while none of the slow acetylators in the PGx-treatment experienced either INH-DILI or early treatment failure. Among the rapid acetylators, early treatment failure was observed with a significantly lower incidence rate in the PGx-treatment than in the STD-treatment (15.0 % vs. 38 %). Thus, the NAT2 genotype-guided regimen resulted in much lower incidences of unfavorable events, INH-DILI or early treatment failure, than the conventional standard regimen. Conclusion: Our results clearly indicate a great potential of the NAT2 genotype-guided dosing stratification of isoniazid in chemotherapy for tuberculosis. [ABSTRACT FROM AUTHOR]

Purpose: Elevated circulating activities of alanine aminotransferase (ALT), a marker for liver injury, and the lifestyle of a higher rate of eating in healthy and preclinical subjects are associated with increased risk of obesity and diabetes. In this study, we examined the associations between self-reported rate of eating and circulating ALT activity in middle-aged apparently healthy Japanese men. Methods: We conducted a cross-sectional study of 3,929 apparently healthy men aged 40-59 years (mean ± SD age, 49.2 ± 5.8 years; BMI, 23.5 ± 2.8 kg/m) who participated in health checkups in Japan. We analyzed their clinical serum parameters and lifestyle factors, including self-reported rate of eating. Associations between self-reported rate of eating and liver injury markers [ALT, γ-glutamyl transpeptidase (GTP), and aspartate aminotransferase (AST)], other clinical parameters or lifestyle factors were determined using analysis of variance followed by Tukey's test. Multivariate logistic regression analyses (MLRA) were performed with ALT activity as the dependent variable and independent variables that included self-reported rate of eating. Results: MLRA showed that ALT activity showed trends for higher self-reported rate of eating after adjustment for age, energy intake, and smoking status. The association between ALT activity and self-reported rate of eating disappeared after adjustment for BMI. Conclusion: The results of this study show that ALT activity is positively associated with self-reported rate of eating in middle-aged apparently healthy Japanese men. [ABSTRACT FROM AUTHOR]

Purpose: In Japan, a national surveillance study of antimicrobial consumption has never been undertaken. This study aimed to describe antimicrobial consumption and resistance to Pseudomonas aeruginosa in 203 Japanese hospitals, to identify targets for quality improvement. Methods: We conducted an ecological study using retrospective data (2010). Antimicrobial consumption was collected in the World Health Organization (WHO) anatomical therapeutic chemical/defined daily dose (ATC/DDD) format. Rates of imipenem (IPM), meropenem (MEPM), ciprofloxacin (CPFX), or amikacin (AMK) resistance were expressed as the incidence of non-susceptible isolates. Additionally, hospitals were asked to provide data concerning hospital characteristics and infection control policies. Hospitals were classified according to functional categories of the Medical Services Act in Japan. Results: Data were collected from 203 Japanese hospitals (a total of 91,147 beds). The total antimicrobial consumption was 15.49 DDDs/100 bed-days (median), with consumptions for penicillins, carbapenems, quinolones, and glycopeptides being 4.27, 1.60, 0.41, and 0.49, respectively. The median incidences of IPM, MEPM, CPFX, and AMK resistance were 0.15, 0.10, 0.13, and 0.03 isolates per 1,000 patient-days, respectively. Antimicrobial notification and/or approval systems were present in 183 hospitals (90.1 %). In the multivariate analysis, the piperacillin/tazobactam, quinolones, and/or total consumptions and the advanced treatment hospitals showed a significant association with the incidence of P. aeruginosa resistant to IPM, MEPM, CPFX, and AMK [adjusted R (a R) values of 0.23, 0.30, 0.22, and 0.35, respectively). Conclusion: This is the first national surveillance study of antimicrobial consumption in Japan. A continuous surveillance program in Japan is necessary in order to evaluate the association among resistance, antimicrobial restriction, and consumption. [ABSTRACT FROM AUTHOR]

Purpose: Although previous studies suggested that higher low-fat dairy consumption lower the risk of type 2 diabetes, the mediating factors are not well understood. Higher baseline adiponectin levels are related with a lower risk of type 2 diabetes. This study evaluated whether low-fat dairy is related with adiponectin in apparently healthy adults. Methods: We investigated a cross-sectional ( n = 938) and one-year longitudinal ( n = 759) relationship between low-fat and whole-/high-fat dairy (both including cow's milk and yogurt) and adiponectin. Dairy consumption was assessed with a validated food frequency questionnaire. Serum adiponectin was measured by using a specific sandwich enzyme-linked immunosorbent assay. Results: In the cross-sectional analysis, the geometric means (95 % confidence intervals [95 % CIs]) of log-transformed adiponectin related with the low-fat dairy categories were 7.27 (6.80-7.77) for the lowest category, 7.67 (7.09-8.31) for the middle category, and 8.40 (7.73-9.13) for the highest category ( p < 0.001) after adjustment for potential confounders (including all lifestyle factors). In the longitudinal analysis, repeated-measures ANCOVA adjusted for confounding factors showed a significant time-by-categories (categories of low-fat dairy) interaction in the change of adiponectin. In contrast, no significant relationship was found between the whole-/high-fat dairy categories and adiponectin. Conclusions: This study has shown that higher consumption of low-fat dairy, but not of whole-/high-fat dairy, is related with higher levels of adiponectin and with the change of adiponectin level at the one-year follow-up. These results suggest that the consumption of low-fat dairy may have a beneficial effect on serum adiponectin levels. [ABSTRACT FROM AUTHOR]

Purpose: Congestive heart failure (CHF) alters the pharmacokinetics of various drugs, including cardiovascular agents, due to decreased cardiac output and decreased renal blood flow. The purpose of this study was to evaluate the influence of CHF on the clearance of vancomycin, a glycopeptide antibacterial agent. Methods: After reviewing more than 1,500 clinical charts of patients who received vancomycin therapy and whose serum vancomycin level was monitored, we identified 101 patients who also had the left ventricular ejection fraction (LVEF) assessed at that time. The fluorescence polarization immunoassay method was used to measure vancomycin serum concentrations in these patients 1 h after the end of vancomycin infusion and just before the next administration. Using these two measurements, we calculated the pharmacokinetic parameters using the Bayesian estimator. Results: Patients with an LVEF of <40 % (16 patients) or those with an LVEF of ≥ 40 % and <60 % (40 % ≤ LVEF < 60 % ; 32 patients) had a significantly lower vancomycin clearance than patients with LVEF of ≥60 % (53 patients) (2.29 ± 0.95 or 2.79 ± 0.99 vs. 3.50 ± 1.04 L/h; p < 0.001 or p < 0.01, respectively). Vancomycin clearance was strongly correlated not only with estimated creatinine clearance (CLcr) in patients with an LVEF of <40 % ( r = 0.828) and 40 % ≤ LVEF < 60 % ( r = 0.773), but also with an LVEF in patients with a CLcr of <60 mL/min ( r = 0.646). Consistent with these findings, multiple regression analysis revealed that CLcr, LVEF and body weight were important independent variables for vancomycin clearance ( r = 0.649). Conclusions: Vancomycin clearance decreased with decreasing cardiac function (LVEF) and decreasing CLcr. This finding suggests that vancomycin clearance is affected by cardiac function and would be predicted not only CLcr but also by LVEF. [ABSTRACT FROM AUTHOR]

To examine the inter-rater reliability of Autism Diagnostic Interview-Revised, Japanese Version (ADI-R-JV), the authors recruited 51 individuals aged 3-19 years, interviewed by two independent raters. Subsequently, to assess the discriminant and diagnostic validity of ADI-R-JV, the authors investigated 317 individuals aged 2-19 years, who were divided into three diagnostic groups as follows: autistic disorder (AD), pervasive developmental disorder not otherwise specified, and other psychiatric diagnosis or no diagnosis, according to the consensus clinical diagnosis. As regards inter-rater reliability, intraclass correlation coefficients of greater than 0.80 were obtained for all three domains of ADI-R-JV. As regards discriminant validity, the mean scores of the three domains was significantly higher in individuals with AD than in those of other diagnostic groups. As regards diagnostic validity, sensitivity and specificity for correctly diagnosing AD were 0.92 and 0.89, respectively, but sensitivity was 0.55 for individuals younger than 5 years. Specificity was consistently high regardless of age and intelligence. ADI-R-JV was shown to be a reliable tool, and has sufficient discriminant validity and satisfactory diagnostic validity for correctly diagnosing AD, although the diagnostic validity appeared to be compromised with respect to the diagnosis of younger individuals. [ABSTRACT FROM AUTHOR]

Purpose: The risk of metabolic syndrome (MetS) is assessed based on the presence of risk factors that include dyslipidemia, hyperglycemia, hypertension and obesity. In this study, we assessed the risk of MetS using principle component (PC) analysis of MetS diagnostic parameters and examined whether the resulting eigenvalues are associated with the circulating concentrations of inflammatory cytokines [interleukin (IL)-1β and IL-6] and a marker for insulin sensitivity (adiponectin) in middle-aged Japanese men without treatment for metabolic diseases. Materials: We conducted a cross-sectional study of 308 Japanese men without treatment for metabolic diseases aged 40-69 years who participated in health checkups in Japan. We calculated the PC1 score from the following MetS diagnostic parameters: body mass index (BMI), fasting blood glucose, diastolic blood pressure, triacylglycerol and high-density lipoprotein cholesterol. We compared the relationship between PC1 scores and other clinical parameters, including IL-1β, IL-6 and adiponectin, by Spearman's rank correlation coefficient analyses and Jonckheere-Terpstra test. Results: The associations for most clinical parameters were higher with the PC1 score than with other MetS diagnostic parameters. Homeostasis model assessment-insulin resistance, an index of insulin resistance, showed stronger associations with PC1 score than with MetS diagnostic parameters. Significant associations for IL-1β, IL-6 and adiponectin were observed with the PC1 score, BMI and triacylglycerol; these associations were higher with the PC1 score than with BMI and triacylglycerol. Conclusions: The present results show that the PC1 score is closely associated with parameters of MetS, inflammation and insulin resistance. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to determine whether individuals with Asperger's disorder exhibit difficulty in switching attention from a local level to a global level. Eleven participants with Asperger's disorder and 11 age- and gender-matched healthy controls performed a level-repetition switching task using Navon-type hierarchical stimuli. In both groups, level-repetition was beneficial at both levels. Furthermore, individuals with Asperger's disorder exhibited difficulty in switching attention from a local level to a global level compared to control individuals. These findings suggested that there is a problem with the inhibitory mechanism that influences the output of enhanced local visual processing in Asperger's disorder. [ABSTRACT FROM AUTHOR]

Summary: Increased levels of serum undercarboxylated osteocalcin, which were associated with bone metabolism markers, correlated inversely with indices of glucose metabolism (plasma glucose, hemoglobin A1C, and glycated albumin) in hemodialysis patients with abnormalities of bone metabolism. Introduction: Undercarboxylated osteocalcin (ucOC), a possible marker of bone metabolism and one of the osteoblast-specific secreted proteins, has recently been reported to be associated with glucose metabolism. We tested the hypothesis that ucOC levels are associated with indices of glucose metabolism in chronic hemodialysis patients with abnormalities of bone metabolism. Methods: Serum ucOC, bone alkaline phosphatase (BAP, a bone formation marker), and tartrate-resistant acid phosphatase-5b (TRACP-5b, a bone resorption marker) were measured in 189 maintenance hemodialysis patients (96 diabetics and 93 non-diabetics), and their relationships with glucose metabolism were examined. Results: ucOC correlated positively with BAP ( ρ = 0.489, p < 0.0001), TRACP-5b ( ρ = 0.585, p < 0.0001) and intact parathyroid hormone (iPTH; ρ = 0.621, p < 0.0001). Serum ucOC levels in the diabetic patients were lower than those of non-diabetic patients ( p < 0.001), although there were no significant differences in serum BAP or TRACP-5b between diabetic and non-diabetic patients. Serum ucOC correlated negatively with plasma glucose ( ρ = −0.303, p < 0.0001), hemoglobin A1C ( ρ = −0.214, p < 0.01), and glycated albumin ( ρ = −0.271, p < 0.001), although serum BAP or TRACP-5b did not. In multiple linear regression analysis, log [plasma glucose], log [hemoglobin A1C], and log [glycated albumin] were associated significantly with log [ucOC] after adjustment for age, gender, hemodialysis duration, and body mass index but were not associated with log [BAP], log [TRACP-5b], or log [intact PTH]. Conclusion: Increased levels of serum ucOC, which were associated with bone metabolism markers, were inversely associated with indices of glucose metabolism in hemodialysis patients. [ABSTRACT FROM AUTHOR]

Meltwater and/or rainfall (MR) were monitored using lysimeters in a mountainous region in the north-central part of Japan, where a seasonal snowpack forms, to collect basic data sets for understanding the MR regime and sediment-related disasters. Statistical analyses of the data over 11 years showed that high hourly MR intensities were mainly observed as rain during the non-snow cover period, but the annual maximum daily MR often occurred during the snow cover period. The longer the time unit, the greater the shift in maximum MR values from the non-snow to snow cover periods. For a time unit of 70 h, almost all maximum values were recorded during snow melting periods. The timing, intensity and duration of MR regulate the characteristics of sediment-related disasters such as debris flows, slope failures and landslides. In the case of deep-seated landslides, if there are no accurate observations of MR during the snow cover period, the degree of risk may be underestimated. Furthermore, when designing groundwater discharge works to prevent deep-seated landslides, the timing, intensity and duration of MR must be accurately evaluated to effectively discharge groundwater during the snow melting period. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to clarify the anatomical and CT imaging features of the parotid duct at the anterior portion near the orifice together with its surrounding structures and to determine appropriate CT slice thicknesses for depicting the duct. Methods: Initially, two cadavers were dissected to clarify the relationship between the duct and its surrounding structures. Next, original urethane phantoms with 2- and 3-mm diameters were scanned. The resultant images were constructed at 0.5-, 2-, and 3-mm slice thicknesses and evaluated, taking the partial volume effect into account. Finally, axial CT images of 190 adult subjects (107 men; 83 women) were analyzed for the relationship between the duct and other structures, together with the types of duct curvature on the axial plane and the slice ranges for the duct's run in the body axis direction. Results: The facial vein, which could always be observed anteriorly to the parotid duct, appeared to be an effective anatomical landmark for identifying the duct. The zygomaticus major muscle and buccal fat pad capsule should be carefully differentiated from the duct. The phantom study revealed that 2-mm slice thickness was appropriate, and this was confirmed in the actual CT images with a high detection rate (98 %). The run of the parotid duct showed three types of curvature within ranges of four slices at 2-mm thickness. Conclusions: On axial CT images constructed at ≤2-mm slice thicknesses, the parotid duct was sufficiently depicted and could be well identified from other structures by reference to the facial vein. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the impact of surgical site infection (SSI) on postoperative resource consumption for colon and rectal open and laparoscopic surgeries after accounting for infection depth and patient characteristics, and to compare these estimates among institutions. Methods: We collected administrative and SSI-related data from eight Japanese hospitals, and used generalized linear models to estimate excess postoperative length of stay (LOS) and charges attributable to SSI. Covariates included wound class, American Society of Anesthesiologists (ASA) score, operation time, emergency, colostomy, trauma, implant, and comorbidities. Results: We examined 1,108 colon surgery (CS) and 477 rectal surgery (RS) patients. For open surgery, the postoperative LOS in non-SSI patients was 13.5 (CS) and 15.9 days (RS). Compared with non-SSI patients, the postoperative LOS increased by 4.5 (CS) and 2.8 days (RS) for superficial SSI, 6.8 (CS) and 8.5 days (RS) for deep SSI, and 7.8 and 9.5 days for space/organ SSI. For laparoscopic surgery, the postoperative LOS was 9.8 (CS) and 14.6 days (RS). SSI was significantly associated with increased postoperative LOS for superficial SSI [by 4.8 (CS) and 3.6 days (RS)], deep SSI [by 10.3 (CS) and 23.9 days (RS)], and space/organ SSI [by 8.9 days (RS)]. The postoperative LOS among hospitals was 3.8-10.4 days (CS) and 1.3-12.2 days (RS). Postoperative SSI-attributable charges ranged from $386 to $2,873, depending on organ, procedure, and infection depth. Conclusion: This study quantified the impact of SSIs on resource consumption and confirmed significant cost variations among hospitals. These variations could not be explained by patient characteristics or infection type. [ABSTRACT FROM AUTHOR]