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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]

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]

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: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]

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]

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]

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]

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: 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: 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]

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]

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]

Purpose: Cancer cachexia is characterized by hypoalbuminemia and with the hepatic production of acute-phase proteins in response to malignant growth. The aim of this study was to evaluate the influence of cachexia on the pharmacokinetic disposition of and clinical responses to oxycodone in cancer patients. Methods: Forty-seven Japanese patients receiving oxycodone extended-release tablets as a starting opioid for cancer pain were enrolled in this study. Cachexia was evaluated using the Glasgow Prognostic Score (GPS). Predose plasma concentrations of oxycodone and noroxycodone were determined at the titration dose. Results: Seven patients had a GPS of 0, 21 a GPS of 1, and 19 had a GPS of 2. A higher GPS was significantly correlated with a higher oxycodone concentration and a lower concentration ratio of noroxycodone to oxycodone and significantly associated with a lower incidence of dose escalation and a higher incidence of central adverse reactions. Serum albumin, but not α-acid glycoprotein and C-reactive protein, was inversely correlated with the free fraction of oxycodone. Serum albumin concentration was significantly associated with the incidence of dose escalation. In contrast, the free fraction of oxycodone and acute-phase proteins were not related to the clinical responses. Conclusions: Cachexia had an effect on oxycodone metabolism and the clinical responses to oxycodone. The observed reduction in serum albumin concentration was associated with dose escalation. These findings suggest that cachexia affects the clinical responses to oxycodone through metabolic and nutritional disorders in cancer patients. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate the association between falls and physiological factors primarilly the toe-gap force and the Good Walker's Index using a path analysis. Three hundred and sixty-two (362) elderly people, over 65 years of age, undertook five types of walking ability and physiological tests, The Toe-gap Force and the Good Walker's Index, which consists of 10-m walking time, Maximal Step Length (MSL), 40/20 cm step test, and tandem gait. Questions concerning demographic characteristics, instrumental activities of daily living (IADL), subjective well-being, long-term care needs, and characteristics of falls were asked. Ninety participants (24.9%) reported one or more falls within the past year. The results showed that a lower toe-gap force and a lower good-walker's Index score were significantly associated with falls. Fallers scored worse on Toe-gap force R, 10-m walking time, and Maximal Step strength. The Good Walker's Index was significantly associated with all test measures. The path analysis model revealed the association between the Good Walker's Index and falls. Toe-gap force and the Good Walker's Index can serve as an effective predictive factor for older people who are living independently in the community. This study provided a model of the inter-relationships among physiological factors such as the Good walker's Index, Toe-gap force and falls, as well as vision and falls. [ABSTRACT FROM AUTHOR]

Background: Appropriate sensitivity threshold of accelerometer to measure total sleep time during nap is not established. Purpose: Actigraphy-derived total sleep times during naps were calculated using three different sensitivity threshold values and compared with polysomnography. Method: The mean age of the 60 subjects (53 men and 7 women) was 22.8, ranging from 22 to 27 years. Determination of the sleep stage by the polygraph and the sleep/wake judgment by the accelerometer obeyed the sleep/wake judgment, and the accelerometer was monitored under different sensitivity threshold settings. The study was carried out during one afternoon with a 3-h nap opportunity. Kappa statistics, correlations, and several indices of accuracy were compared using statistical methods. Results: The mean total sleep times during a nap set for 180 min were 160.4, 151.8, and 140.5 min, respectively, as judged under the low-sensitive, middle-sensitive, high-sensitive settings of an accelerometer worn on the non-dominant wrist. The corresponding mean total sleep time as calculated using a sleep polygraph was 133.0 min. Sleep/wake judgment by three levels of threshold values for the accelerometer showed that high-sensitive threshold showed relatively high specificity (0.452) compared with specificities by the low-sensitive threshold (0.249) or by the middle-sensitive threshold (0.358). The concordance correlation coefficients and 95% confidence intervals (in parenthesis) between the total sleep time judged by polygraph and low-sensitive, middle-sensitive, or high-sensitive accelerometer were 0.40 (0.26-0.51), 0.53 (0.38-0.65), and 0.64 (0.49-0.75), respectively. The Bland-Altman plot of the measurements showed higher agreement between the total sleep time by polygraph and by the accelerometer using the high-sensitive threshold. Conclusions: From the result obtained in this study, the high-sensitive accelerometer showed the strongest agreement of total sleep time and sleep/wake judgment with the calculated value using the sleep polygraph. [ABSTRACT FROM AUTHOR]

Background: Individuals with irritable bowel syndrome (IBS) have high anxiety. There is insufficient information about the relationships between concrete cognitive contents and anxiety in IBS. Purpose: The present study investigated the relationship between cognitive factors and anxiety in individuals with IBS. Method: The participants were 1,087 college students (male, 506; female, 576; unidentified, 5; age, 19.72 ± 1.76 years) who completed a set of questionnaires that included the Rome II Modular Questionnaire (based on diagnostic criteria for IBS), Anxiety Sensitivity Index (ASI), Cognitive Appraisal Rating Scale (CARS; subscales: commitment, appraisal of effect, appraisal of threat, and controllability) for measuring symptom-related cognition, an item about attention to abdominal symptoms, the Hospital Anxiety and Depression Scale-Anxiety Scale (HADS-A), and an item regarding the presence of avoidant behavior due to anxiety of IBS symptoms. Results: The participants included 881 individuals without IBS and 206 individuals with IBS. Individuals with IBS had higher ASI and HADS-A scores than those of the individuals belonging to the control group ( p < 0.001). Subscale scores of CARS (except those of controllability and attention to IBS symptoms) significantly correlated with the ASI and HADS-A scores ( p < 0.01). Individuals with IBS and avoidant behavior had higher subscale scores of CARS (except those of controllability and attention to IBS symptoms) and higher HADS-A scores ( p < 0.05). The hypothetical models containing ASI scores, subscale scores of CARS (except those of controllability), and HADS-A scores with and without attention to IBS symptoms exhibited a good fit. Conclusion: Severe anxiety sensitivity in individuals with IBS related to their symptom-related cognition, and the altered cognition increases anxiety, leading to the possible development of a disabling condition. [ABSTRACT FROM AUTHOR]

Background: The change (Δ) in the low-density lipoprotein cholesterol (LDL-C) / high-density lipoprotein cholesterol (HDL-C) ratio ( ΔLDL-C/HDL-C) and obesity are known to play important roles in the progression of coronary atherosclerosis. We hypothesized that a reasonable predictive model of coronary plaque regression could be constructed using ΔLDL-C/HDL-C and the body mass index (BMI). Objective: The purpose of this study was to establish a predictive model of coronary plaque regression using ΔLDL-C/HDL-C and BMI. Methods and Results: A 6-month prospective observational study was conducted among 114 patients with coronary artery disease (CAD) who were treated with pravastatin. The plaque volume, as assessed using volumetric intravascular ultrasound, decreased significantly by 9.9 % (p < 0.0001 vs baseline). In a multi-variate regression analysis with traditional risk factors, ΔLDL-C/HDL-C (β: 0.473, p = 0.0001) and the baseline BMI (β : 0.249, p= 0.004) were identified as independent predictors of the Δplaque volume. The patients were divided using the 50th percentile of the baseline BMI and the 50th percentile of the ΔLDL-C/HDL-C ratio as cutoffs, and a model for predicting coronary atherosclerotic regression was prepared using a combination of the two variables. The Δplaque volumes were -18.3 %, -14.1 %, -4.8%, and - 2.2% for the groups with ΔLDL-C/HDL-C≤-22.2 % and a BMI ≤ 24.1 kg /m², ΔLDL-C/HDL-C≤-22.2 % and ΔBMI >24.1 kg /m², ΔLDL-C/HDL-C>-22.2 % and BMI ≤ 24.1 kg /m² and ΔLDL-C/HDL-C>-22.2 % and BMI >24.1 kg /m², respectively (p = 0.003). Conclusion: A predictive model for coronary plaque regression based on a combination of ΔLDL-C/HDL-C and the baseline BMI may be a useful clinical tool in patients with CAD. [ABSTRACT FROM AUTHOR]

Summary: This study aims to determine the relationship between advanced glycation end-product (AGE) accumulation in skin tissue and bone strength, assessed by quantitative ultrasound, among healthy adult Japanese men. The results of the study suggest that men with higher AGE accumulation in skin tissue have a lower osteo-sono assessment index. Introduction: AGE accumulate in bone collagen with age and diabetes and decrease the mechanical properties of bone. Although increased AGE levels are associated with fractures among diabetic patients and elderly women, it is unclear whether a relationship between increased AGE levels and bone strength is present in apparently healthy adult males. The aim of this study was to determine the relationship between AGE accumulation in tissue and the mechanical properties of bone among adult Japanese men, using quantitative ultrasound as a surrogate measure of the latter. Methods: Skin autofluorescence (AF), which is a noninvasive method for measuring tissue AGEs, and osteo-sono assessment index (OSI), which is determined by quantitative ultrasound, were measured in 193 adult Japanese men (median age 43 years; interquartile range 37.0-55.0 years). Results: Adjusted for age, BMI, calcium intake, physical activity, smoking status, and education level, log-transformed skin AF had a negative association with log-transformed OSI ( β = −0.218, P < 0.01). Adjusted geometric means (95% CI) for OSI across the tertiles of skin AF were 2.81 (2.75-2.87) for the lowest tertile, 2.81 (2.74-2.87) for the middle tertile, and 2.66 (2.61-2.73) for the highest tertile; thus, OSI for the highest skin AF appeared to be 5.0% lower than that for the lowest and middle skin AF tertiles ( P < 0.01). Conclusion: Among apparently healthy adult Japanese men, those with higher skin AF had a lower OSI, indicating a relationship between AGE accumulation and bone strength. A long-term prospective study is required to clarify the causality. [ABSTRACT FROM AUTHOR]

Purpose: This study was designed to investigate the antisecretory activity of rabeprazole administered once daily in doses of 5, 10, 20, and 40 mg and different cytochrome P450 2C19 (CYP2C19) genotypes on gastric pH in healthy individuals. Additional objectives were delineating the nighttime from the daytime effect and determining the relationships between the pharmacokinetics and pharmacodynamics of rabeprazole. Methods: Eight individuals of each of the three genotypes of CYP2C19-homozygous extensive metabolizers (homo-EMs), heterozygous EMs (hetero-EMs), and poor metabolizers (PMs)-were recruited. Twenty-four individuals received a once-daily dose, with dosing interval 24 h of 5, 10, 20, or 40 mg rabeprazole for 5 days in a 4-period crossover fashion. Twenty-four-hour intragastric pH and plasma rabeprazole concentrations were determined on day 5. Results: A dose-dependent increase in median pH and in pH 4 holding time was observed across all CYP2C19 genotypes. When rabeprazole was increased from 20 mg to 40 mg, the differences and 95% confidence intervals (CIs) of nighttime pH 4 holding time between 40 mg and 20 mg in homo-EMs, hetero-EMs, and PMs were 8.0% (−5.0% − 21.0%), 28.7% (15.7% − 41.6%), and 16.9% (3.9% − 29.9%), respectively. The relationship between the area under the plasma concentration-time curve up to the last time point at which rabeprazole was quantifiable (AUC) and the pH 4 holding time could be described using a sigmoid maximum effect (E) model. Conclusions: Our data demonstrate that increasing rabeprazole dose up to 40 mg once daily results in an increasing pharmacodynamic effect, which is most apparent for the control of nocturnal gastric acid secretion. [ABSTRACT FROM AUTHOR]

Study design:Case control.Objective:To clarify the predictors of low blood pressure (BP) and hyponatremia after spinal cord injury (SCI) and to discuss their pathophysiology.Setting:A SCI center in Japan.Methods:Age, gender, initial ASIA impairment scale (AIS) score, BP, blood electrolytes (sodium, K and Cl) and biochemical markers were evaluated at 1 month after injury. Risk factors of low BP and hyponatremia were analyzed using uni- and multivariate logistic regression models.Results:This study comprised of 172 SCI patients. Initial AIS score (Odds ratio (OR): 1.24, 95% confidence intervals (CI) 1.13-1.49, P-value <0.01) and hyponatremia (OR: 3.71, 95%CI 1.27-6.96, P<0.01) were the most important risk factors of low BP. As a second step, risk factors of hyponatremia were initial AIS score (OR: 1.36, 95%CI 1.08-2.78, P<0.01) and age (OR: 1.55, 95%CI 1.17-2.93, P<0.01).Conclusions:In acute and subacute period, the more severe SCI and lower AIS score patients have the more frequently low BP and/or hyponatremia do appear. [ABSTRACT FROM AUTHOR]

Study design:A prospective clinical cohort study.Objectives:To test if maximum voluntary ventilation (MVV), which is currently underutilized in diseases, serves for assessing subclinical ventilatory impairment in cervical spondylotic myelopathy (CSM).Setting:Kochi Medical School, Japan.Methods:We studied ventilatory function in 49 CSM patients and 20 age- and sex-matched control patients with either lumbar stenosis or lower limb osteoarthritis. All patients underwent ventilatory function studies consisting of flow volume curves, vital capacity (VC) and the MVV in 12 s before and after surgery. Tetraparesis was assessed by the functional scale of the Japanese Orthopaedic Association (JOA).Results:The CSM group had significantly smaller %forced VC , %peak expiratory flow rate (%PEFR) and %MVV than the control group preoperatively. In contrast to the control group, the CSM group showed a significant increase in %MVV from 74.9±18.7% preoperatively to 80.3±19.0% postoperatively (P<0.005), but not in any other ventilatory measures. This postoperative increase in %MVV significantly correlated with the JOA score (r=0.493; P<0.001). As a possible effect of diaphragmatic recovery, the %PEFR significantly increased postoperatively only in patients with the primary site of involvement at or rostral to C3-4.Conclusion:Of the various ventilatory measurements, MVV was most sensitive to changes in tetraparesis in CSM, presumably because MVV, unlike the other ventilatory measures, reflects the coordination in addition to the strength of respiratory muscles. [ABSTRACT FROM AUTHOR]

Purpose: Orally administered bovine lactoferrin (bLF) exerts an anti-inflammatory effect on hepatitis and colitis animal models. To investigate the mechanism underlying the action of bLF, we explored the expression of inflammation-related factors in the intestine of a hepatitis mouse model after the oral administration of bLF and in several human intestinal cell lines treated with bLF. Methods: The effects of bLF on the expression of interleukin-11 (IL-11) and bone morphogenetic protein 2 (BMP2) in the intestinal mucosa of a hepatitis mouse model as well as in cell cultures of human intestinal epithelial cells, myofibroblasts, and monocytes were examined using the real-time reverse transcription polymerase chain reaction. Epithelial cells and myofibroblasts were also cocultured using transwells. bLF transport, and IL-11 and BMP2 induction, as well as the interactions between the two cell types, were then analyzed after bLF treatment. Results: In vivo, oral bLF administration increased the production of IL-11 and BMP2 in intestinal specimens. In vitro, bLF only stimulated the production of IL-11 in human intestinal myofibroblasts; i.e., it had no effect on BMP2 production in any cell type. In the transwell cocultures, bLF passed through the epithelium and directly stimulated IL-11 production in the myofibroblasts on the basolateral side. The IL-11 produced in the myofibroblasts subsequently acted protectively on the epithelial cells of the coculture. Conclusions: bLF upregulated the activity of anti-inflammatory factors, such as IL-11, in the intestine of a hepatitis mouse model and human intestinal myofibroblasts. [ABSTRACT FROM AUTHOR]

Lifestyle-related chronic diseases such as cancer and cardiovascular disease are the greatest public health concerns. Evidence shows Japanese immigrants to a westernized environment have higher incidence of lifestyle-related diseases. However, little is known about lifestyle characteristics related to chronic diseases for Japanese in a westernized environment. This study is examining the gap in lifestyle by comparing the lifestyle prevalence for Japanese in the US with the Japanese National Data (the National Health and Nutrition Survey in Japan, J-NHANS) as well as the Japan National Health Promotion in the twenty-first Century (HJ21) goals. Japanese adults were surveyed in Pittsburgh, USA, regarding their lifestyle (e.g., diet, exercise, smoking, stress, alcohol, and oral hygiene). The prevalence was compared with J-NHANS and HJ21 goals. Ninety-three responded (response rate; 97.9%). Japanese men ( n = 38) and women ( n = 55) in Pittsburgh smoke less than Japanese in Japan ( P < 0.001 for both genders). Japanese in Pittsburgh perform less physical activity in daily life and have lower prevalence of walking more than 1 h per day ( P < 0.001 for both genders). Japanese women in Pittsburgh have significantly higher prevalence of stress than in Japan ( P = 0.004). Japanese men in Pittsburgh do not reach HJ21 goal in weight management, BMI, use of medicine or alcohol to sleep, and sleep quality. Japanese women in Pittsburgh do not reach HJ21 goal in weight management and sleep quality. In conclusion, healthy lifestyle promotion including exercise and physical activity intervention for Japanese living in a westernized environment is warranted. [ABSTRACT FROM AUTHOR]

It remains elusive what factors affect posterior reversible encephalopathy syndrome (PRES). Eleven PRES children, all with acute glomerulonephritis, Alport syndrome, and lupus nephritis, 5 with nephrosis, and 3 renal transplant recipients, were studied. PRES recurred in 1 patient. Neurological symptoms were graded as 1: mild (headache, nausea/vomiting, or tremor), 2: moderate (vision change), and 3: severe (mental dysfunction, cerebellar symptoms, seizures, recurrence of seizures, and coma). Magnetic resonance imaging was graded as 1: subtle change, 2: abnormal large areas, and 3: complete involvement of the regions. The common symptoms were seizures (100%), headache (82%), nausea/vomiting (73%), coma (55%), and vision change (46%). Seizures recurred in 7 (64%). All but one (91%) developed hypertension and 7 (64%) received calcineurin inhibitors (CNI). Edema occurred in 7 (64%) and renal insufficiency/end-stage renal disease (ESRD) in 4 (36%). Seizures recurred frequently in younger patients. Symptoms were severe in girls. Duration or severity of the condition with predisposing factors (hypertension, CNI, nephrosis or renal insufficiency/ERSD) did not make a difference in the symptoms and neuroimaging. Two patients developed chronic epilepsy. Age and gender may affect PRES symptoms. Our results are limited by small sample size and should be determined using larger numbers of patients. [ABSTRACT FROM AUTHOR]

Summary: Recent animal studies have demonstrated that undercarboxylated osteocalcin upregulates insulin secretion via osteoblast-insulin signaling. However, it remains unclear whether such a pathway exists in humans. This study showed that serum undercarboxylated osteocalcin levels were inversely associated with fasting plasma glucose, hemoglobin A, and homeostasis model assessment of insulin resistance (HOMA-IR) levels in community-dwelling elderly Japanese men. Introduction: Undercarboxylated osteocalcin (ucOC) was reported to increase insulin secretion and improve glucose tolerance via osteoblast-insulin signaling in animal-based studies. Whether this pathway also exists in humans is unknown. We aimed to clarify whether serum ucOC levels are associated with glycemic status and insulin resistance in the general Japanese population. Methods: We included 2,174 Japanese men (≥65 years) who were able to walk without aid from others and lived at home in four cities of Nara Prefecture. We excluded participants with a history of diseases or medications that affect bone metabolism, other than type 2 diabetes mellitus (T2DM). Fasting plasma glucose, glycated hemoglobin A, and HOMA-IR levels were determined as outcome measures. Results: Of the 1,597 participants included in the analysis, both intact OC (iOC) and ucOC levels showed significant inverse correlations with all outcome measures, even after adjusting for potential confounders. Mean values of outcome measures showed a significant decreasing trend with higher quintiles of iOC or ucOC after adjusting for confounders. This trend remained significant for ucOC quintiles after further adjustment for iOC levels, but was not significant for iOC quintiles after adjusting for ucOC levels. These results were attenuated, but still apparent, after excluding participants receiving drug therapy for T2DM. Conclusions: Levels of ucOC, but not iOC, were inversely associated with glycemic index and insulin resistance in a population of Japanese men. These findings will need to be confirmed with longitudinal studies. [ABSTRACT FROM AUTHOR]

Summary: A cross-sectional analysis of 1,662 community dwelling elderly Japanese men suggested that habitual natto intake was significantly associated with higher bone mineral density (BMD). When adjustment was made for undercarboxylated osteocalcin levels, this association was insignificant, showing the natto-bone association to be primarily mediated by vitamin K. Introduction: Low vitamin K intake is associated with an increased risk of hip fracture, but reports have been inconsistent on its effect on BMD. Our first aim was to examine the association between BMD and intake of fermented soybeans, natto, which contain vitamin K1 (20 μg/pack) and K2 (380 μg/pack). Our second aim was to examine the association between undercarboxylated osteocalcin (ucOC), a biomarker of vitamin K intake, and BMD to evaluate the role of vitamin K in this association. Methods: Of the Japanese men aged ≥65 years who participated in the baseline survey of the Fujiwara-kyo Osteoporosis Risk in Men study, 1,662 men without diseases or medications known to affect bone metabolism were examined for associations between self-reported natto intake or serum ucOC levels with lumbar spine or hip BMD. Results: The subjects with greater intake of natto showed significantly lower level of serum ucOC. Analysis after adjustment for confounding variables showed an association of greater intake of natto with both significantly higher BMD and lower risk of low BMD (T-score < −1 SD) at the total hip and femoral neck. This association became insignificant after further adjustment for ucOC level. Conclusion: Habitual intake of natto was associated with a beneficial effect on bone health in elderly men, and this association is primarily due to vitamin K content of natto, although the lack of information on dietary nutrient intake, including vitamin K1 and K2, prevented us from further examining the association. [ABSTRACT FROM AUTHOR]

It is important to identify premature infants with prenatal inflammation as it contributes to short- and long-term complications. Our object was to study how prenatal inflammation affects the urinary β-microglobulin (β-MG) level. Preterm neonates were divided based on the presence of chorioamnionitis (CAM) into the CAM ( n = 100) and non-CAM groups ( n = 117). These were further subdivided into five groups each: 30 preterm neonates of 23-26; 42 neonates of 27-28; 54 neonates of 29-30; 51 neonates of 31-32; and 40 neonates of 33-34 weeks' gestation. The urinary β-MG level within 48 h of birth was significantly higher in the CAM group than in the non-CAM group among the neonates of 23-26 weeks' gestation (18.3 ± 6.9 vs 10.0 ± 5.6 × 10 μg/gCr, p = 0.0018) and the neonates of 27-28 weeks' gestation (16.2 ± 10.8 vs 8.8 ± 3.3 × 10 μg/gCr, p = 0.0101). However, there was no difference in urinary β-MG level between the CAM and the non-CAM group among the neonates ≥ 29 weeks 'gestation. Moreover, the elevated urinary β-MG level in the neonates ≤ 28 weeks ' gestation with CAM had disappeared by 1 week after birth. The reasons for the increase in urinary β-MG level within 48 h of birth in very preterm neonates (≤ 28 weeks' gestation) with CAM are believed to be not only prematurity, but also prenatal inflammation. It is suggested that the urinary β-MG level during the early postnatal period can identify prenatal inflammation. [ABSTRACT FROM AUTHOR]

Study design:Non-randomized study.Objectives:Previous studies indicated that at least 2-h leg exercise at more than 60% maximum oxygen consumption (VO2max) increased plasma interleukin (IL)-6 in able-bodied (AB) subjects. The purpose of the present study was to compare IL-6 response to arm exercise in AB subjects and persons with spinal cord injury (SCI).Setting:Wakayama Medical University in Japan.Methods:Six subjects with SCI between T6 and T10 and seven AB subjects performed 2-h arm crank ergometer exercise at 60%VO2max. Plasma catecholamines, IL-6, tumor necrosis factor (TNF)-α and high-sensitivity C-reactive protein (hsCRP) were measured before exercise, 60-min exercise, immediately and 2 h after the completion of exercise.Results:Arm exercise increased myoglobin and plasma IL-6 levels in SCI and AB (P<0.01), but there were no differences in them between the two groups throughout the study. Plasma levels creatine kinase, lactate dehydrogenase, TNF-α and hsCRP did not change throughout the study in both groups.Conclusion:These findings suggest neither significant muscle damage nor inflammatory response during exercise. The increase in plasma IL-6 in SCI was not unexpected, confirming that moderate intensity and relatively long-arm exercise is safe and beneficial for SCI subjects with regard to IL-6 excretion, as in AB subjects. [ABSTRACT FROM AUTHOR]

The purpose of this study was to clarify the importance of public health nurses (PHNs) in Japan assigned to the targets and methods of public health nursing activities. Subjects were PHNs who had 10 years or more of work experience. A cross-sectional written survey was used to collect data from 1,967 PHNs (42% response rate). Survey items sought opinions on trends in community health and welfare activities (TCHWA), and the importance of public health nursing activities. TCHWA responses indicated that 70% or more of participants recognized the expansion of public responsibility, and the importance of the individual level of practice and policy-making. Surveyed PHNs found coordinating an organization (83.6%) to be important. Correlation of responses regarding TCHWA and the importance of public health nursing activities highlighted the importance of policy-making and indicated a significantly high awareness of the importance of activities. PHNs regarded support at both the individual/family and population/community levels to be important in terms of public health nursing activities. Currently, regarding public health nursing activities, it is necessary to promote the role of safety nets for protecting citizens' health, and effective public health nursing activities from which all citizens can equitably resource. [ABSTRACT FROM AUTHOR]

n effective treatment for children with refractory nephrotic syndrome (NS), especially in those with cyclosporine (CsA)-resistant or CsA-intolerant NS, has yet to be established. Recently, the efficacy of multidrug therapy consisting of tacrolimus (Tac), mycophenolate mofetil (MMF) in combination with prednisolone (PDN) in adult patients with refractory NS has been reported. We successfully treated 14 consecutive children with refractory CsA-resistant or CsA-intolerant NS using combination therapy consisting of relatively low-dose Tac, mizoribine (MZR), which has a mechanism of action very similar to that of MMF, and PDN. There were no serious clinical toxicities. Of the 14 children, 9 with a mean age of 13.0 years had steroid-dependent NS (SDNS) and 5 with a mean age of 9.6 years had steroid-resistant NS (SRNS). All SDNS patients had minimal change disease (MCD), 4 with SRNS had focal segmental glomerulosclerosis (FSGS), and the remaining child had MCD on renal biopsy. All patients were in a prospective cohort, but were evaluated retrospectively. The mean follow-up from the initiation of multidrug therapy was 18.4 months in SDNS and 18.6 months in SRNS patients. At the last observation point, the calculated relapse rate and minimum dose of PDN required for maintenance of clinical remission after the start of multidrug therapy were significantly decreased compared with those prior to this therapy, while on CsA, in SDNS patients (0.4 ± 0.5 times/year vs 2.9 ± 1.5 times/year, P = 0.0077, and 0.3 ± 0.2 mg/kg on alternate days vs 0.5 ± 0.2 mg/kg on alternate days, P = 0.0184 respectively). All SDNS and two SRNS patients (40%) achieved complete remission, allowing further decreases in the minimal doses of PDN required for maintenance of clinical remission in most our patients. However, one patient with FSGS remained refractory to multidrug therapy and subsequently developed end-stage renal disease. These clinical observations, although preliminary and involving a small number of patients, suggest that multidrug therapy consisting of relatively low-dose Tac, MZR, and PDN might be effective and safe for treating children with refractory CsA-resistant or CsA-intolerant NS. However, further studies involving larger numbers of patients are needed. [ABSTRACT FROM AUTHOR]

Summary: Improvements in total content of enzymatic cross-linking, the ratio of hydroxylysine-derived enzymatic cross-links, and non-enzymatic advanced glycation end product cross-link formation from once-weekly administration of hPTH(1-34) for 18 months in OVX cynomolgus monkeys contributed to the improvement of bone strength. Introduction: Parathyroid hormone (PTH) is used for the treatment of osteoporosis. To elucidate the contribution of material properties to bone strength after once-weekly treatment with hPTH(1-34) in an ovariectomized (OVX) primate model, the content of collagen and enzymatic immature, mature, and non-enzymatic cross-links, collagen maturity, trabecular architecture, and mineralization in vertebrae were simultaneously estimated. Methods: Adult female cynomolgus monkeys were divided into four groups ( n = 18-20 each) as follows: SHAM group, OVX group, and OVX monkeys given once-weekly subcutaneous injections of hPTH(1-34) either at 1.2 or 6.0 μg/kg (low- or high-PTH groups) for 18 months. The content of collagen, enzymatic and non-enzymatic cross-linking pentosidine, collagen maturity, trabecular architecture, mineralization, and cancellous bone strength of vertebrae were analyzed. Results: Low-PTH and high-hPTH treatments increased the content of enzymatic immature and mature cross-links, bone volume (BV/TV), and trabecular thickness, and decreased pentosidine, compared with the OVX group. Stepwise logistic regression analysis revealed that BV/TV, the content of total enzymatic cross-links, and calcium content independently affected ultimate load (model R = 0.748, p < 0.001) and breaking energy (model R = 0.702, p < 0.001). BV/TV was the most powerful and enzymatic cross-link content was the second powerful determinant of both ultimate load and breaking energy. The most powerful determinant of stiffness was the enzymatic cross-link content (model R = 0.270, p < 0.001). Conclusion: Once-weekly preventive administration of hPTH(1-34) increased the total contents of immature and mature enzymatic cross-links, which contributed significantly to vertebral cancellous bone strength. [ABSTRACT FROM AUTHOR]

Summary: A high circulating osteoprotegerin (OPG) level may be a risk factor for vascular calcification and mortality in hemodialysis patients. OPG and pulse wave velocity (PWV) were measured at baseline in 151 normoalbuminemic, long-term (>3 years) Japanese hemodialysis patients who were prospectively followed for 6 years. In long-term normoalbuminemic Japanese hemodialysis patients, OPG levels were strongly linked with both arterial stiffness and worse outcome. Introduction: A high circulating OPG level is reported to be a risk factor for vascular calcification and mortality in Western chronic kidney disease (CKD) patients but it is not known if this is true for Japanese CKD patients, where a different risk profile may operate. Methods: OPG and PWV were measured at baseline in 151 normoalbuminemic, long-term (>3 years) Japanese hemodialysis patients (median age 62 years) who were prospectively followed for 6 years. Results: OPG levels were associated in multivariate analysis with age, dialysis vintage, history of cardiovascular disease (CVD) and parathyroid hormone levels. C-reactive protein levels did not correlate with OPG. Patients with clinical history of CVD had significantly higher OPG levels and OPG levels were positively correlated to PWV, an index of arterial stiffness. These associations were independent of age, sex, dialysis vintage, and diabetes. During the follow-up period, 40 deaths, including 25 cardiovascular deaths, were recorded. In crude analysis, each unit of increase in OPG was associated with increased all-cause (hazard ratios 1.14, 95% confidence interval 1.08-1.20) and CVD mortality (1.14 [1.07-1.21]), which persisted after adjustment for age, sex, dialysis vintage, diabetes, and baseline CVD (1.12 [1.05-1.19] and 1.11 [1.02-1.19], all-cause and CVD mortality, respectively). Conclusions: In long-term normoalbuminemic Japanese hemodialysis patients, with low prevalence of inflammation, OPG levels were strongly linked with both arterial stiffness and worse outcome. [ABSTRACT FROM AUTHOR]

Summary: This study investigated the role of macrophage migration inhibitory factor (MIF) in fracture repair using MIF gene-deficient mice (MIF KO). Fracture healing was delayed in MIF KO, and this was mainly due to the delay in the mineralization of osteoid within the fracture callus. Introduction: We previously reported that the expression of macrophage migration inhibitory factor (MIF) was up-regulated during the fracture healing process in rats. However, its role in the pathophysiology of this process remained unclear. The aim of the present study was to clarify the role of MIF in the fracture healing process using MIF gene-deficient mice (MIF KO). Methods: Bone repair in wild-type mice (WT) and MIF KO ( n = 70, respectively) was investigated using a tibia fracture model. Radiographic, biomechanical, histological, bone histomorphometric, and molecular analyses were performed. Results: Post-fracture biomechanical testing showed that maximum load and stiffness were significantly lower in MIF KO than in WT on day 42. However, similar levels were observed between the two groups on day 84. Bone histomorphometric analysis revealed significantly higher osteoid volume, a lower mineral apposition rate, and smaller numbers of osteoclasts in the MIF KO callus compared to the WT callus. The messenger ribonucleic acid expressions of matrix metalloproteinase (MMP)-2, membranous type 1-MMP, cathepsin K, and tissue nonspecific alkaline phosphatase were found to be significantly suppressed in the MIF KO callus. Conclusion: The results of the present study suggest that delayed fracture healing in MIF KO was mainly attributable to a delay in osteoid mineralization. [ABSTRACT FROM AUTHOR]

Purpose: Coffee is among the most widely consumed beverages in the world. Numerous epidemiological studies have reported a significant inverse association between coffee consumption and risk of type 2 diabetes mellitus, but the underlying mechanisms are still not fully understood. Therefore, we conducted an epidemiological study to clarify the relationship between coffee consumption and adiponectin levels in Japanese males. We also evaluated whether green tea consumption affected adiponectin levels. Methods: We carried out a cross-sectional study. The subjects were 665 male employees in Japan. Coffee consumption was assessed, using a self-administered questionnaire, as the number of times per week and cups per day respondents drank, and subjects were grouped into four levels (non, 1-5 times/week, 1-2 cups/day and ≥3 cups/day). Results: The means of adiponectin levels were positively associated with coffee consumption. A dose-response relationship was found between coffee consumption and circulating adiponectin levels. The relationship remained significant after adjustment for potential confounding factors ( P for trend <0.05). However, green tea consumption was not significantly associated with adiponectin levels ( P for trend = 0.90). Conclusions: We not only revealed that habitual coffee consumption is associated with higher adiponectin levels in Japanese males but also found a dose-dependent association between coffee consumption and adiponectin levels. Therefore, our study suggested that coffee components might play an important role in the elevation of adiponectin level. [ABSTRACT FROM AUTHOR]

Summary: Postmenopausal hemodialysis patients are at risk of complications related to renal mineral and bone disorder, and postmenopausal osteoporosis. In 112 postmenopausal hemodialysis patients, free estrogen index was positively correlated with bone mineral density (BMD) Z-score and the annual percent change of BMD in multiple regression analysis. Endogenous estrogen may prevent bone loss in postmenopausal hemodialysis patients throughout life. Introduction: Women on dialysis are not only at risk of developing mineral and bone disorder, but also suffer from postmenopausal osteoporosis. We assessed the effect of sex hormones on bone metabolism in postmenopausal hemodialysis patients. Methods: We enrolled 112 postmenopausal hemodialysis patients with a mean age of 68.4 ± 10.4 years. We measured the serum levels of estradiol, testosterone, sex hormone-binding globulin (SHBG), and intact parathyroid hormone (intact-PTH), as well as bone metabolism parameters and radial bone mineral density (BMD). The free estrogen index (FEI) was calculated from the estradiol and SHBG values. After conventional dialysis was performed for 12 months, BMD was measured again and the annual percent change was calculated. Estradiol and SHBG were also measured in 25 postmenopausal women without chronic kidney disease. Results: Estradiol levels were higher in the hemodialysis patients than in the postmenopausal women without chronic kidney disease. In patients with relatively normal bone turnover (intact-PTH: from 150 to 300 pg/ml), the FEI showed a positive correlation with the BMD Z-score. The annual percent change of BMD showed a positive correlation with the FEI according to multiple regression analysis. Conclusions: Endogenous estrogen may prevent bone loss in postmenopausal hemodialysis patients throughout life. [ABSTRACT FROM AUTHOR]

Summary: Although previous studies indicated that serum insulin-like growth factor-I (IGF-I) was inversely associated with the presence of vertebral fractures (VFs), little is known whether serum IGF-I is associated with multiple VFs. We report that serum IGF-I could be clinically useful for assessing the severity of VFs in type 2 diabetic postmenopausal women. Introduction: The number of VFs is associated with the mobility and mortality of the elderly people. Although serum IGF-I is inversely associated with the presence of VFs, little is known about the relationship between serum IGF-I and multiple VFs. Methods: In this cross-sectional study, we recruited 479 men and 334 postmenopausal women with type 2 diabetes mellitus and measured serum IGF-I, bone mineral density, and bone turnover markers. Lateral X-ray films of the thoracic and lumbar spine were taken to diagnose the VF. Results: In postmenopausal women, serum IGF-I level was decreased when the number of VFs was increased [no VFs; 138 ± 51 ng/ml (mean ± SD) vs. one VF; 119 ± 42 ( p = 0.006), two VFs; 103 ± 39 ( p = 0.002), and three and more VFs; 91 ± 40 ( p < 0.001)]. Multiple logistic regression analysis adjusted for age, duration of diabetes, body mass index, serum creatinine, and HbA showed that serum IGF-I level was inversely associated with the presence of one VF [odds ratio (OR) = 0.67, p = 0.029], two VFs (OR = 0.40, p = 0.017), as well as three and more VFs (OR = 0.27, p = 0.005). These associations were still significant after the additional adjustment for BMD at the lumbar spine. In contrast, no significant association of serum IGF-I level with VFs was found in men. Conclusions: Serum IGF-I level was inversely associated with the number of prevalent VFs in postmenopausal women with type 2 diabetes, suggesting that serum IGF-I could be clinically useful for assessing the severity of VFs in the population. [ABSTRACT FROM AUTHOR]

Objective:The aim of this study was to assess the genetic effects of the vascular endothelial growth factor (VEGF) pathway on retinopathy of prematurity (ROP).Study Design:A prospective study from a tertiary center that enrolled 204 Japanese infants (<35 weeks of gestational age (GA)) having no anomalies. ROP developed in 127, but not in 77 infants. The relative severity was defined as non-severe, moderate and severe ROP for GA, based on the staging criteria. VEGF (g.−634G>C, g.+13553C>T) and VEGF-receptor (KDR g.+4422(AC)11 to 14, Flt-1 c.+6724(TG)13 to 23) gene polymorphisms and clinical variables were assessed by uni/multivariate analyses.Result:The frequency of polymorphisms did not differ between ROP and non-ROP patients. The TT genotype of g.+13553 showed a higher odds ratio for non-severe ROP than CC genotype (P=0.006). Multivariate analyses indicated that low birth weight, blood transfusion and respiratory distress syndrome, but not polymorphisms, were the risk factors of advanced ROP (stage 3).Conclusion:A genotype of the VEGF pathway weakly affects the severity of ROP compared with other clinical factors. [ABSTRACT FROM AUTHOR]

Study design:An in vivo study in a rat model of acute spinal cord contusion.Objectives:To assess the efficacy of novel therapies for acute spinal cord injury (SCI), methods to evaluate accurately the effects of these therapies should be developed. Although neurological examination is commonly used for this purpose, unstable clinical conditions and the spontaneous recovery of neurological function in the acute and subacute phases after injury make this measurement unreliable. Recent studies have reported that the phosphorylated form of the high-molecular-weight neurofilament subunit NF-H (pNF-H), a new biomarker for axonal degeneration, can be measured in serum samples in experimental SCI animals. Therefore, we aimed to investigate the use of plasma pNF-H as an indicator of the efficacy of minocycline, a neuroprotective drug, for treating SCI.Setting:This study was carried out at Saitama, Japan.Methods:Spinal cord injured rats received either minocycline or saline intraperitoneally. The plasma pNF-H levels and functional hind limb score were determined after the injury.Results:Minocycline treatment reduced plasma pNF-H levels at 3 and 4 days post-injury (dpi). Rats with lower plasma pNF-H levels at 3 dpi had higher hind limb motor score at 28 dpi.Conclusions:pNF-H levels may serve as a biomarker for evaluating the efficacy of therapies for SCI. [ABSTRACT FROM AUTHOR]

Summary: In cinacalcet treatment of hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT), not only intact parathyroid hormone (I-PTH), whole PTH (W-PTH), and bone markers, but also W-PTH/I-PTH ratio as proportion of active PTH(1-84) molecules were decreased. Changes in W-PTH/I-PTH ratio significantly correlated and predicted changes in bone marker. Introduction: Cinacalcet partly suppresses the secretion of PTH by enhancing PTH(1-84) degradation into N-truncated fragments. The objectives of this study is to investigate the significance of the N-truncated PTH/PTH(1-84) ratio for the prediction of the effect of cinacalcet in HD patients. Methods: Serum parameters were measured during 12 weeks of oral cinacalcet administration at 25 mg daily in 39 HD patients with SHPT. Results: Serum Ca, Pi, W-PTH, I-PTH, and W-PTH/I-PTH ratio all decreased significantly in a time-dependent manner during cinacalcet administration. Serum tartrate-resistant acid phosphatase (TRAP) 5b reflected these changes more precisely than serum N-telopeptide of type-I collagen. At 1 week, changes in I-PTH and W-PTH correlated significantly with those in serum Pi, but not Ca. Changes in serum Pi (but not Ca) and serum W-PTH also correlated significantly with changes in serum TRAP5b at both 4 and 12 weeks, while changes in serum I-PTH correlated significantly with those in serum TRAP5b only at 12 weeks. Changes in the serum W-PTH/I-PTH ratio correlated significantly with those in serum TRAP5b at both 4 and 12 weeks, and changes in serum W-PTH/I-PTH ratio at 4 weeks showed a tendency for a correlation with changes in serum TRAP5b at 12 weeks. HD patients with a reduced W-PTH/I-PTH ratio after 4 weeks had a significantly greater reduction of TRAP5b over 12 weeks. Conclusion: W-PTH and the W-PTH/I-PTH ratio allow estimation of the potency of cinacalcet in enhancement of PTH degradation, and thus no less reliable markers than I-PTH for reflecting cinacalcet-induced bone resorption. [ABSTRACT FROM AUTHOR]

Introduction: It is important to know whether a parotid gland lesion is in the superficial or deep lobe for preoperative planning. We aimed to investigate the ability of 3.0 T magnetic resonance (MR) imaging with surface coils to identify the intraparotid facial nerve and locate parotid gland lesions, in comparison to other indirect landmark methods. Methods: We retrospectively evaluated 50 consecutive patients with primary parotid gland lesions. The position of the facial nerve was determined by tracing the nerve in the stylomastoid foramen and then following it on sequential MR sections through the parotid gland. The retromandibular vein and the facial nerve line (FN line) were also identified. For each radiologist and each method, we determined the diagnostic ability for deep lobe lesions and superficial lobe lesions, as well as accuracy. These abilities were compared among the three methods using the Chi-square test with Yates' correction. Results: Mean diagnostic ability for deep lobe lesions, the diagnostic ability for superficial lobe lesions, and accuracy were 92%, 86%, 87%, respectively, for the direct identification method; 67%, 89%, 86%, respectively, for the retromandibular vein method; and 25%, 99%, 90% , respectively, for the FN line method. The direct identification method had significantly higher diagnostic ability for deep lesions than the FN line method ( P < 0.01), but significantly lower diagnostic ability for superficial lobe lesions than the FN line method ( P < 0.01). Conclusion: Direct identification of the intraparotid facial nerve enables parotid gland lesions to be correctly located, particularly those in the deep lobes. [ABSTRACT FROM AUTHOR]

Summary: A reference database for trabecular bone density, cortical thickness, and elastic modulus of trabecular bone for a novel ultrasonic bone densitometry system (LD-100) based on two longitudinal waves (fast and slow) was determined over a wide age range in a normal Japanese population. Introduction: A novel ultrasonic bone densitometry system (LD-100 system) was applied to create a reference database for trabecular bone density (TBD), cortical thickness (CoTh), and elastic modulus of trabecular bone (EMTb) for this device over a wide age range in a normal Japanese population. Methods: In a comparative study between LD-100 and peripheral quantitative computed tomography (pQCT) systems, 52 individuals were examined by both systems at the same radius simultaneously. To create a reference database, a total of 2,380 healthy subjects (1,179 men, 1,201 women), ages 18–99 years, were examined using the LD-100 system. Results: Highly significant correlations between the LD-100 and pQCT systems were found in TBD ( r = 0.877, p < 0.001) and CoTh ( r = 0.723, p < 0.001). For the reference database, peak values of TBD, CoTh, and EMTb were observed at 30–34 years (255.09 mg/cm), 20–24 years (5.23 mm), and 20–24 years (4.09 GPa) in men, and at 25–29 years (209.24 mg/cm), 25–29 years (3.98 mm), and 20–24 years (3.33 GPa) in women, respectively. The TBD fell significantly ( p < 0.05) beginning at 55–59 years in both sexes, with a relatively rapid decrease in women. The CoTh showed a significant decrease beginning at 40–44 years in men and 50–54 years in women. The EMTb showed a significant decrease beginning at 40–44 years in men and 55–59 years in women. Conclusions: The LD-100 system is a useful bone densitometry device and the database of age-related changes in TBD, CoTh, and EMTb established in this study will provide fundamental data for future studies related to bone status. [ABSTRACT FROM AUTHOR]

Introduction: The effects of aging on brain volume are generally investigated using voxel-based morphometry (VBM) or the manually traced region-of-interest (ROI) method. We introduce an atlas-based method as a methodological alternative that calculates absolute volume as a non-biased and semi-automatic whole-brain technique. Methods: We enrolled 115 healthy females (mean age, 36.7 years) and 130 healthy males (mean age, 37.1 years). Volume data were acquired using a 1.5 tesla magnetic resonance scanner. After spatial normalization, a lobar-based atlas template was applied, and the absolute volumes of the frontal, temporal, parietal, and occipital lobes and the sublobar and limbic areas were calculated bilaterally. The effects of age on regional brain volume were evaluated statistically. Results: The volume of all ROIs declined linearly with increasing age. The bilateral frontal lobes showed the steepest involution. Analysis of variance revealed significant laterality and interaction of gender and age. Conclusion: The atlas-based method introduced in the present study has advantages over the manually traced ROI method in its objectivity, coverage, and time requirement and has an advantage over the VBM method in its computability of absolute volume. The results are largely in agreement with those reported previously, thereby reconfirming the importance of matching gender and age in analyzing brain disorders. [ABSTRACT FROM AUTHOR]