超伝導技術を応用した近未来船

Background: Low back pain (LBP) is one of the most disabling and costly disorders affecting modern society, and approximately 90% of patients are labelled as having non-specific LBP (NSLBP). Several interventions for patients with NSLBP have been assessed in clinical trials, but heterogeneous reporting of outcomes in these trials has hindered comparison of results and performance of meta-analyses. Moreover, there is a risk of selective outcome reporting bias. To address these issues, the development of a core outcome set (COS) that should be measured in all clinical trials for a specific health condition has been recommended. A standardized set of outcomes for LBP was proposed in 1998, however, with evolution in COS development methodology, new instruments, interventions, and understanding of measurement properties, it is appropriate to update that proposal. This protocol describes the methods used in the initial step in developing a COS for NSLBP, namely, establishing a core domain set that should be measured in all clinical trials. Methods/Design: An International Steering Committee including researchers, clinicians, and patient representatives from four continents was formed to guide the development of this COS. The approach of initiatives like Core Outcome Measures in Effectiveness Trials (COMET) and Outcome Measures in Rheumatology (OMERACT) was followed. Participants were invited to participate in a Delphi study aimed at generating a consensus-based core domain set for NSLBP. A list of potential core domains was drafted and presented to the Delphi participants who were asked to judge which domains were core. Participant suggestions about overlap, aggregation, or addition of potential core domains were addressed during the study. The patients' responses were isolated to assess whether there was substantial disagreement with the rest of the Delphi panel. A priori thresholds for consensus were established before each Delphi round. All participants' responses were analysed from a quantitative and qualitative perspective to ascertain that no substantial discrepancies between the two approaches emerged. Discussion: We present the initial step in developing a COS for NSLBP. The next step will be to determine which measurement instruments adequately cover the domains

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Peer reviewe

Expression of hypoxia-inducible factor-1a (HIF-1a) in pituitary tumours

The present study was performed to investigate HIF-1a (hypoxia-inducible factor-1a) expression in a large number of immunohistochemically and ultrastructurally characterized surgically removed pituitary tumours. The potential relation of HIF-1a with outcome variables as well as the presence of HIF-1a expression in the tumours treated with dopamine agonists and octreotide, a long-acting somatostatin analogue was also investigated. HIF-1a immunoreactivity was confined to the nucleoplasm whereas the nucleoli were unconspicuous. The distribution of HIF-1a was evident in the tumours whereas normal adenohypophysial cells showed no HIF- 1a staining. HIF-1a expression was detected not only in the tumour cells but also in endothelial cells lining the blood vessels within the tumour. ACTH producing adenomas showed the lowest level of HIF-1a expression whereas pituitary carcinomas and GH producing adenomas had the highest counts. The statistical study demonstrated no significant correlation between HIF-1a expression, patient age, gender, tumour, size, invasiveness, cell proliferation rate and vascularity. These results suggest that the behaviour of pituitary tumours does not primarily depend of HIF-1a expression. Our study demonstrated an increase HIF-1a expression in bromocriptine treated PRL producing pituitary adenomas compared with untreated tumours but no increase in octreotide treated tumours

Immunoexpression of androgen receptor in the nontumorous pituitary and in adenomas

PubMedID: 18228161Little information is available regarding androgen receptor immunoexpression (AR) in the normal and neoplastic human pituitary. Available experimental data links it to primarily gonadotroph cells. We undertook an immunohistochemical study of 41 autopsy-derived normal glands from patients of both sexes and all ages as well as 79 fully characterized pituitary adenomas of all types, the focus being upon AR expression in normal and neoplastic gonadotrophs. Nuclear AR immunoreactivity was noted in gonadotrophs and other normal adeno- and neurohypophysial cells. In addition to its presence in 74% of gonadotroph and 55% of null cell adenomas, lesser proportions of other adenoma types (adrenocorticotropic hormone 50%, prolactin 38%, growth hormone 33%) also exhibited AR immunoreactivity. No staining of thyroid-stimulating hormone adenomas was noted. The physiologic significance of our findings remains to be explored. The literature regarding AR expression in animal and human pituitaries is reviewed. © 2008 Humana Press Inc

Adrenomedullin expression in pituitary adenomas and nontumoral adenohypophyses

Summary. Adrenomedullin (ADM) is a novel peptide originally identified in extracts of human pheochromocytoma. It is produced by several tissues, including the pituitary gland. The presence of ADM has been immunohistochemically demonstrated in pathologic pituitary glands, but no systematic study of ADM expression in human pituitary adenomas has been reported. Thus, we investigated ADM immunoexpression in 88 various hormone-secreting and clinically nonfunctioning pituitary adenoma types as well as 30 nontumoral adenohypophyses. Furthermore, ADM immunoreactivity was assessed on a 0 to +3 scale in all samples. We found strong immunoreativity for ADM in normal gonadotrophs also expressing FSH and LH whereas in the other adenohypophysial cell types expression of ADM was mild. Results showed that normal adenohypophyses were strongly immunopositive for ADM (2.18±0.11). Our findings demonstrate that ADM expression in the anterior pituitary is diminished in tumors as compared to the normal gland. The physiologic function of ADM is unknown, but it could act as a paracrine or autocrine factor in the adenohypophysis

Polycystic ovarian syndrome: marked differences between endocrinologists and gynaecologists in diagnosis and management

The definitive version is available at www.blackwell-synergy.comBackground Women with polycystic ovarian syndrome (PCOS) commonly consult endocrinologists or gynaecologists and it is not known whether these specialty groups differ in their approach to management. Objective To compare the investigation, diagnosis and treatment practices of endocrinologists and gynaecologists who treat PCOS. Design and Setting A mailed questionnaire containing a hypothetical patient's case history with varying presentations − oligomenorrhoea, hirsutism, infertility and obesity − was sent to Australian clinical endocrinologists and gynaecologists in teaching hospitals and private practice. Results Evaluable responses were obtained from 138 endocrinologists and 172 gynaecologists. The two specialty groups differed in their choice of essential diagnostic criteria and investigations. Endocrinologists regarded androgenization (81%) and menstrual irregularity (70%) as essential diagnostic criteria, whereas gynaecologists required polycystic ovaries (61%), androgenization (59%), menstrual irregularity (47%) and an elevated LH/FSH ratio (47%) (all P-values < 0·001). In investigation, gynaecologists were more likely to request ovarian ultrasound (91%vs. 44%, P < 0·001) and endocrinologists more likely to measure adrenal androgens (80%vs. 58%, P < 0·001) and lipids (67%vs. 34%, P < 0·001). Gynaecologists were less likely to assess glucose homeostasis but more likely to use a glucose tolerance test to do so. Diet and exercise were chosen by most respondents as first-line treatment for all presentations. However, endocrinologists were more likely to use insulin sensitizers, particularly metformin, for these indications. In particular, for infertility, endocrinologists favoured metformin treatment whereas gynaecologists recommended clomiphene. Conclusions There is a lack of consensus between endocrinologists and gynaecologists in the definition, diagnosis and treatment of PCOS. As a consequence, women may receive a different diagnosis or treatment depending on the type of specialist consulted.Andrea J. Cussons, Bronwyn G. A. Stuckey, John P. Walsh, Valerie Burke and Robert J. Norma

A consensus approach toward the standardization of back pain definitions for use in prevalence studies

A modified Delphi study conducted with 28 experts in back pain research from 12 countries. OBJECTIVE. To identify standardized definitions of low back pain that could be consistently used by investigators in prevalence studies to provide comparable data. SUMMARY OF BACKGROUND DATA. Differences in the definition of back pain prevalence in population studies lead to heterogeneity in study findings, and limitations or impossibilities in comparing or summarizing prevalence figures from different studies. METHODS. Back pain definitions were identified from 51 articles reporting population-based prevalence studies, and dissected into 77 items documenting 7 elements. These items were submitted to a panel of experts for rating and reduction, in 3 rounds (participation: 76%). Preliminary results were presented and discussed during the Amsterdam Forum VIII for Primary Care Research on Low Back Pain, compared with scientific evidence and confirmed and fine-tuned by the panel in a fourth round and the preparation of the current article. RESULTS. Two definitions were agreed on a minimal definition (with 1 question covering site of low back pain, symptoms observed, and time frame of the measure, and a second question on severity of low back pain) and an optimal definition that is made from the minimal definition and add-ons (covering frequency and duration of symptoms, an additional measure of severity, sciatica, and exclusions) that can be adapted to different needs. CONCLUSION. These definitions provide standards that may improve future comparisons of low back pain prevalence figures by person, place and time characteristics, and offer opportunities for statistical summaries