bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sleep Apnea and Daytime Sleepiness and Fatigue: Relation to Visceral Obesity, Insulin Resistance, and Hypercytokinemia
Authors: Vgontzas Alexandros N. , Papanicolaou Dimitris A. , Bixler Edward O. , Hopper Kenneth , Lotsikas Angela , Lin Huong-Mo , Kales Anthony , Chrousos George P. 
Published: January 2014

Abstract
Sleep apnea and associated daytime sleepiness and fatigue are common manifestations of mainly obese middle-aged men. The onset of sleep apnea peaks in middle age, and its morbid and mortal sequelae include complications from accidents and cardiovascular events. The pathophysiology of sleep apnea remains obscure. The purpose of this study was to test three separate, albeit closely related, hypotheses. 1) Does sleep apnea contribute to the previously reported changes of plasma cytokine (tumor necrosis factor-α and interleukin-6) and leptin levels independently of obesity? 2) Among obese patients, is it generalized or visceral obesity that predisposes to sleep apnea? 3) Is apnea a factor independent from obesity in the development of insulin resistance? Obese middle-aged men with sleep apnea were first compared with nonapneic age- and body mass index (BMI)-matched obese and age-matched lean men. All subjects were monitored in the sleep laboratory for 4 consecutive nights. We obtained simultaneous indexes of sleep, sleep stages, and sleep apnea, including apnea/hypopnea index and percent minimum oxygen saturation. The sleep apneic men had higher plasma concentrations of the adipose tissue-derived hormone, leptin, and of the inflammatory, fatigue-causing, and insulin resistance-producing cytokines tumor necrosis factor-α and interleukin-6 than nonapneic obese men, who had intermediate values, or lean men, who had the lowest values. Because these findings suggested that sleep apneics might have a higher degree of insulin resistance than the BMI-matched controls, we studied groups of sleep-apneic obese and age- and BMI-matched nonapneic controls in whom we obtained computed tomographic scan measures of total, sc, and visceral abdominal fat, and additional biochemical indexes of insulin resistance, including fasting plasma glucose and insulin. The sleep apnea patients had a significantly greater amount of visceral fat compared to obese controls (&lt;0.05) and indexes of sleep disordered breathing were positively correlated with visceral fat, but not with BMI or total or sc fat. Furthermore, the biochemical data confirmed a higher degree of insulin resistance in the group of apneics than in BMI-matched nonapneic controls. We conclude that there is a strong independent association among sleep apnea, visceral obesity, insulin resistance and hypercytokinemia, which may contribute to the pathological manifestations and somatic sequelae of this condition.
Insulin, Androgen, and Gonadotropin Concentrations, Body Mass Index, and Waist to Hip Ratio in the First Years after Menarche in Girls with Regular Menstrual Cycles, Irregular Menstrual Cycles, or Oligomenorrhea1
Authors: van Hooff M. H. A. , Voorhorst F. J. , Kaptein M. B. H. , Hirasing R. A. , Koppenaal C. , Schoemaker J. 
Published: January 2014

Data on changes in hormone concentrations during the first years after menarche are scarce. We studied the relation between gynecological age (age minus age at menarche), hormone concentrations, and body measurements from the 1st to the 6th yr after menarche in 229 observations of girls with regular menstrual cycles, 157 observations of girls with irregular menstrual cycles, and 104 observations of girls with oligomenorrhea.Body Mass Index, waist circumference, hip circumference, LH, androstenedione, testosterone, and dehydro-epiandrosterone sulphate increased significantly (linear regression, P &lt; 0.05) by gynecological age in all menstrual cycle pattern groups. For PRL and estradiol a significant increase with gynecological age was only documented in the regular menstrual cycle group and for waist to hip ratio only in the irregular menstrual cycle group. No significant correlation could be documented between gynecological age and overnight fasting insulin concentrations or glucose to insulin ratio.We found no significant correlation between insulin concentrations or glucose to insulin ratio and androgen concentrations. Significant positive correlations were found between LH and androgens.LH and androgen levels increase during the first years after menarche, and reference values should be adjusted for gynecological age. In these years, no significant correlation between hyperinsulinemia and hyperandrogenemia could be documented.
Detection of Binding and Blocking Autoantibodies to the Human Sodium-Iodide Symporter in Patients with Autoimmune Thyroid Disease*
Authors: Ajjan Ramzi A. , Kemp E. Helen , Waterman Elizabeth A. , Watson Philip F. , Endo Toyoshi , Onaya Toshimasa , Weetman Anthony P. 
Published: January 2014

Abstract
The sodium iodide symporter (NIS) is a novel autoantigen in autoimmune thyroid disease (ATD). A recent study has described the development of a bioassay for human (h) NIS antibody detection, but this will not detect antibodies that bind the symporter without modulating its activity. Therefore, the establishment of a binding assay is of importance to determine the overall prevalence of hNIS antibodies in ATD patients. An in vitro transcription and translation system was used to produce [35S]-labeled hNIS. The radiolabeled ligand reacted specifically in immunoprecipitation experiments with rabbit antiserum raised against a peptide fragment of hNIS. Subsequently, the reactivity of control and ATD sera to translated [35S]hNIS was determined using RIAs.
A significant difference in the frequency of hNIS antibody-positive sera was found when patients with either Graves’ disease (GD) or autoimmune hypothyroidism (AH) were compared with normal controls (P = 0.01 and P = 0.03, respectively). Of 49 GD and 29 AH sera tested, 11 (22%) and 7 (24%), respectively, were found to contain hNIS antibodies. Differences were also significant when the antibody-binding indices of the control group of sera were compared with those of both the GD and the AH patient sera (P &lt; 0.0001 and P = 0.001, respectively). In contrast, sera from 10 patients with Addison’s disease and 10 patients with vitiligo (without associated ATD) were all negative for antibody reactivity to the symporter. No differences were detected when the antibody binding indices of either the Addison’s disease or the vitiligo sera were compared with those of the normal sera group (P = 0.9 and P = 0.6, respectively).
Eight of the 11 (73%) GD and 3 of the 7 (43%) AH sera, which were positive for hNIS antibodies in the immunoprecipitation assay, were also found to inhibit iodide uptake in hNIS-transfected CHO-K1 cells, suggesting the existence of antibodies in some serum samples that bind to the symporter without modulating its function. Overall, a significant correlation was found between the iodide uptake inhibition and the binding assays for hNIS antibody detection (r = 0.49, P &lt; 0.0001).
In summary, we have developed a specific and quantitative assay for the detection of hNIS binding antibodies in sera of patients with ATD. This system offers the advantage of studying antibody reactivity against conformational epitopes and will be useful in understanding the role of NIS autoreactivity in the pathogenesis of ATD.
Estrogen Replacement Therapy in a Man with Congenital Aromatase Deficiency: Effects of Different Doses of Transdermal Estradiol on Bone Mineral Density and Hormonal Parameters
Authors: Rochira Vincenzo , Faustini-Fustini Marco , Balestrieri Antonio , Carani Cesare 
Published: January 2014

AbstractThe effects of different doses of transdermal estradiol (TE) on bone mineral density (BMD) in a man with aromatase deficiency were evaluated. The study protocol was divided in the following four phases: phase 1, before estradiol treatment; phase 2, 50 μg TE twice weekly for 6 months; phase 3, 25 μg TE twice weekly for 9 months; and phase 4, 12.5 μg TE twice weekly for 9 months. X-rays of hands, legs, and pelvis were performed, and BMD of the lumbar spine, hormonal parameters (LH, FSH, testosterone, and estradiol), and markers of bone turnover were determined during each phase.BMD in phase 1 was 0.933 g/cm2 and increased to 1.051 and 1.173 g/cm2 after 4 and 7 months of TE, respectively. In phase 3, BMD reached the maximum value (1.275 g/cm2). In phase 4, BMD decreased to 1.180 g/cm2 and was 1.029 g/cm2 at the end of the study protocol. A bilateral necrosis of femoral heads was also detected by x-ray films.In phase 1 serum testosterone was in the normal range, whereas serum estradiol was undetectable. During the 24-month period of treatment with TE (phases 2–4), estradiol was directly related to the amount of TE, whereas LH was inversely related to estradiol serum levels. Estradiol and gonadotropins reached optimal values only in phase 3, when FSH also was near normal; serum testosterone concentrations were normal in phases 3 and 4.This study confirms the role of estrogens in achieving and maintaining bone mineral content in the human male, providing further clinical tools useful in the management of bone loss in aromatase deficiency in the male. We suggest that the adequate substitutive dose of TE for maintaining both bone mass and normal estradiol serum levels in adult men with aromatase deficiency may be 25 μg twice weekly (0.47 μg/kg weekly).
Signal Transduction Characteristics of the Corticotropin-Releasing Hormone Receptors in the Feto-Placental Unit
Authors: Karteris E. , Grammatopoulos D. , Randeva H. , Hillhouse E. W. 
Published: January 2014

AbstractPlacentally derived CRH plays a major role in the mechanisms controlling human pregnancy and parturition. In this study, we sought to investigate the signal transduction mechanisms of CRH Type-1 receptors in the feto-placental unit. To clarify the signal transduction components in placenta and fetal membranes, we investigated the expression of G proteins and adenylate cyclase.Using the nonhydrolysable photoreactive analog [α-32P] GTP-azidoanilide and peptide antisera raised against G proteinα -subunits, we studied coupling of CRH receptors to G proteins in both placental and fetal membranes. Treatment of placental membranes with human CRH (100 nm) increased the labeling of Gq, Go, and Gz but not Gi and Gs. Treatment of fetal membranes with human CRH (100 nm) increased the labeling of Go and Gq but not Gi, Gs, and Gz. These results were supported by experiments that showed that CRH failed to activate adenylate cyclase in these tissues, but induced an increase in inositol phosphates instead. These findings provide new insights into the components of the signal transduction machinery in both fetal and placental membranes and suggest that CRH Type-1 receptors can couple to different G proteins in different tissues. The physiological significance of these observations remains to be elucidated.
Comparison of Alendronate and Intranasal Calcitonin for Treatment of Osteoporosis in Postmenopausal Women*
Authors: Downs Jr. Robert W. , Bell Norman H. , Ettinger Mark P. , Walsh Brian W. , Favus Murray J. , Mako Barbara , Wang Lixia , Smith Mary E. , Gormley Glenn J. , Melton Mary E. 
Published: January 2014

AbstractThis study compared the effects of oral alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women. Women at least 5 yr postmenopause (n = 299) were randomized to either 10 mg alendronate, matching alendronate placebo, or open-label intranasal calcitonin 200 IU daily for 12 months. Hip and spine bone mineral density (BMD) and markers of bone turnover were measured, and safety and tolerability were assessed. Alendronate produced greater increases in BMD than calcitonin at 12 months at the lumbar spine (5.16% vs. 1.18%; P &lt; 0.001), trochanter (4.73% vs. 0.47%; P &lt; 0.001), and femoral neck (2.78% vs. 0.58%; P&lt; 0.001). Changes in BMD with calcitonin were greater than with placebo at the femoral neck, but were not different from placebo at either the trochanter or lumbar spine. Greater decreases in bone turnover were seen with alendronate than with calcitonin (serum bone-specific alkaline phosphatase, 43% vs. 9%, P &lt; 0.001; urinary N-telopeptide, 62% vs. 11%, P &lt; 0.001). Similar percentages of patients in each group reported an adverse experience during the study. We conclude that, in postmenopausal women with osteoporosis, 12 months of therapy with alendronate produced significantly greater increases in BMD of the hip and spine and greater decreases in bone turnover than intranasal calcitonin.
Peroxisome Proliferator-Activated Receptor-γ2 P12A and Type 2 Diabetes in Canadian Oji-Cree*
Authors: Hegele Robert A. , Cao Henian , Harris Stewart B. , Zinman Bernard , Hanley Anthony J. G. , Anderson Carol M. 
Published: January 2014

Abstract
Among the Oji-Cree of northern Ontario, we previously identified a novel variant in the HNF1A gene, namely G319S, that was strongly associated with type 2 diabetes. However, the majority of subjects with diabetes did not have the HNF1A S319 variant, suggesting that there might be other genetic determinants of diabetes susceptibility. In the course of sequencing candidate genes in diabetic subjects who were homozygous for HNF1A G319/G319, we found that some of them had the PPARG A12 variant. After genotyping PPARG in the entire adult Oji-Cree population, we found that: 1) PPARG A12 was strongly associated with type 2 diabetes in women, but not men; 2) among women, the odds of being affected for carriers of PPARG A12 compared with noncarriers was 2.3 (95% confidence interval, 1.4–3.8); and 3) among women, affected carriers of PPARG A12 had a significantly earlier age-of-onset and/or age-at-diagnosis compared with noncarriers. When taken together with the previously reported association of diabetes with HNF1A in both men and women, the gender-specific association with PPARG A12 confirms that type 2 diabetes is etiologically complex in the Oji-Cree and that at least two genes are involved in determining susceptibility to the disease in these people.
Continuation of Growth Hormone (GH) Therapy in GH-Deficient Patients during Transition from Childhood to Adulthood: Impact on Insulin Sensitivity and Substrate Metabolism
Authors: Nørrelund Helene , Vahl Nina , Juul Anders , Møller Niels , Alberti K. G. M. M. , Skakkebæk Niels E. , Christiansen Jens Sandahl , Jørgensen Jens Otto Lunde 
Published: January 2014

Abstract
The appropriate management of GH-deficient patients during transition from childhood to adulthood has not been reported in controlled trials, even though there is evidence to suggest that this phase is associated with specific problems in relation to GH sensitivity. An issue of particular interest is the impact of GH substitution on insulin sensitivity, which normally declines during puberty.
We, therefore, evaluated insulin sensitivity (euglycemic glucose clamp) and substrate metabolism in 18 GH-deficient patients (6 females and 12 males; age, 20 ± 1 yr; body mass index, 25 ± 1 kg/m2) in a placebo-controlled, parallel study. Measurements were made at baseline, where all patients were on their regular GH replacement, after 12 months of either continued GH (0.018 ± 0.001 mg/kg·day) or placebo, and finally after 12 months of open phase GH therapy (0.016 mg/kg·day). Before study entry GH deficiency was reconfirmed by a stimulation test. During the double-blind phase, insulin sensitivity and fat mass tended to increase in the placebo group [ΔM-value (mg/kg·min), −0.7 ± 1.1 (GH) vs. 1.3 ± 0.8 (placebo), P = 0.18; ΔTBF (kg), 0.9 ± 1.2 (GH) vs. 4.4 ± 1.6 (placebo), P = 0.1]. Rates of lipid oxidation decreased [Δlipid oxidation (mg/kg·min), 0.02 ± 0.14 (GH) vs. −0.32 ± 0.13 (placebo), P&lt; 0.05], whereas glucose oxidation increased in the placebo-treated group (P &lt; 0.05). In the open phase, a decrease in insulin sensitivity was found in the former placebo group, although they lost body fat and increased fat-free mass [M-value (mg/kg·min), 5.1 ± 0.7 (placebo) vs. 3.4 ± 1.0 (open), P = 0.09]. In the group randomized to continued GH treatment almost all hormonal and metabolic parameters remained unchanged during the study.
In conclusion, 1) discontinuation of GH therapy for 1 yr in adolescent patients induces fat accumulation without compromising insulin sensitivity; and 2) the beneficial effects of continued GH treatment on body composition in terms of decrease in fat mass and increase in fat-free mass does not fully balance the direct insulin antagonistic effects.
Visceral Adipose Tissue Is an Independent Correlate of Glucose Disposal in Older Obese Postmenopausal Women1
Authors: Brochu Martin , Starling Raymond D. , Tchernof André , Matthews Dwight E. , Garcia-Rubi Ernesto , Poehlman Eric T. 
Published: January 2014

Older obese postmenopausal women have an increased risk for type 2 diabetes and cardiovascular disease. Increased abdominal obesity may contribute to these comorbidities. There is considerable controversy, however, regarding the effects of visceral adipose tissue as a singular predictor of insulin resistance compared to the other constituents of adiposity. To address this issue, we examined the independent association of regional adiposity and total fat mass with glucose disposal in obese older postmenopausal women. A secondary objective examined the association between glucose disposal with markers of skeletal muscle fat content (muscle attenuation) and physical activity levels.
We studied 44 healthy obese postmenopausal women between 50 and 71 yr of age (mean ± sd, 56.5 ± 5.3 yr). The rate of glucose disposal was measured using the euglycemic/hyperinsulinemic clamp technique. Visceral and sc adipose tissue areas and midthigh muscle attenuation were measured from computed tomography. Fat mass and lean body mass were estimated from dual energy x-ray absorptiometry. Peak VO2 was measured from a treadmill test to volitional fatigue. Physical activity energy expenditure was measured from indirect calorimetry and doubly labeled water.
Pearson correlations indicated that glucose disposal was inversely related to visceral adipose tissue area (r = −0.40; P &lt; 0.01), but not to sc adipose tissue area (r = 0.17), total fat mass (r = 0.05), midthigh muscle attenuation (r = 0.01), peak VO2 (r = −0.22), or physical activity energy expenditure (r = −0.01). The significant association persisted after adjusting visceral adipose tissue for fat mass and abdominal sc adipose tissue levels (r = −0.45; P &lt; 0.005; in both cases). Additional analyses matched two groups of women for fat mass, but with different visceral adipose tissue levels. Results showed that obese women with high visceral adipose tissue levels (283 ± 59 vs. 137 ± 24 cm2; P &lt; 0.0001) had a lower glucose disposal per kg lean body mass compared to those with low visceral adipose tissue levels (0.44 ± 0.14 vs. 0.66 ± 0.28 mmol/kg·min; P &lt; 0.05).
Visceral adipose tissue is an important and independent predictor of glucose disposal, whereas markers of skeletal muscle fat content or physical activity exhibit little association in obese postmenopausal women.
The Prevalence and Characteristics of Colorectal Neoplasia in Acromegaly
Authors: Renehan Andrew G. , Bhaskar Pudhupalayan , Painter John E. , O’Dwyer Sarah T. , Haboubi Najib , Varma Jag , Ball Stephen G. , Shalet Stephen M. 
Published: January 2014

Abstract
An increased prevalence of colorectal neoplasia has been reported in acromegalic patients, and recommendations have been made for early colonoscopic screening and regular surveillance. This assumption, however, is frequently drawn from studies using selected control populations. To clarify colonoscopic management in these patients, we undertook a 2-center prospective screening colonoscopy study in 122 acromegalics (age range, 25–82 yr). In the absence of ideal age-matched controls, we calculated prevalence rates of occult adenocarcinomas and adenomas in the general population using cumulative data in the published literature from 8 autopsy studies (model 1, n = 3559) and 4 screening colonoscopy studies (model 2, n = 810), applying linear regression models. Of the 115 patients with complete examinations, adenocarcinomas were discovered in 3 (2.6%), and at least 1 adenoma was found in 11, giving an overall prevalence of neoplasia of 12% (14 of 115). Prevalence rates for age bands 30–40, 40–49, 50–59, 60–69, and 70+ yr were 0%, 8%, 12%, 20%, and 21%, respectively. Compared with the 2 control models, the prevalence of occult colorectal cancer was not significantly increased (acromegalics vs. models 1 and 2, 2.6% vs. 2.3% and 0.9%), nor was there an increase in the prevalence of adenomas in any age band. Pathological characteristics showed some differences, in that adenomas in acromegalics tended to be right sided (68% vs. 57% and 56%), larger (for ≥10 mm, 27% vs. 13% and 9%), and of advanced histology (for tubulovillous, 27% vs. 4% and 22%). No associations were found between the presence of colonic neoplasia and the duration of disease, total GH exposure, cure status, and serum insulin-like growth factor I. This study has failed to demonstrate an increased prevalence of neoplasia in acromegalic patients compared with the expected prevalence in the general population and questions the need for an aggressive colonoscopic screening policy.
Bone Size and Volumetric Density in Women with Anorexia Nervosa Receiving Estrogen Replacement Therapy and in Women Recovered from Anorexia Nervosa
Authors: Karlsson Magnus K. , Weigall Susan J. , Duan Yunbo , Seeman Ego 
Published: January 2014

AbstractAnorexia nervosa is associated with bone loss during adulthood, but may also delay skeletal growth and mineral accrual during growth. We asked the following questions. 1) Is anorexia nervosa associated with reduced bone size and reduced volumetric bone mineral density (vBMD)? 2) Is estrogen replacement therapy (ERT) or recovery from anorexia nervosa associated with normal bone size and vBMD?Using dual-energy x-ray absorptiometry, we measured bone size and vBMD of the third lumbar vertebra and femoral neck in a cross-sectional study of 161 female patients: 77 with untreated anorexia nervosa, 58 with anorexia nervosa receiving ERT, 26 recovered from anorexia nervosa, and 205 healthy age-matched controls. Results were expressed as the sd or z-score (mean ± sem).Deficits in vertebral body and femoral neck width in untreated women were −1.0 ± 0.1 and −0.3 ± 0.1 sd (P &lt; 0.001 and P &lt; 0.05, respectively). Deficits in bone width were less in the ERT-treated women than in untreated women at the vertebral body (−0.6 ± 0.1 sd; P &lt; 0.001), but not at the femoral neck (−0.4 ± 0.2 sd;P &lt; 0.05). There were no significant deficits in vertebral body and femoral neck width in recovered women (both −0.3 ± 0.2 sd; P = NS). In untreated women, vertebral and femoral neck vBMD were −1.6 ± 0.1 and −1.1 ± 0.1 sd, respectively (both P &lt; 0.001), less severely reduced in ERT-treated women (−1.2 ± 0.2 and −0.6 ± 0.2 sd, respectively; both P &lt; 0.001), and least reduced in recovered women (−0.6 ± 0.1 and −0.5 ± 0.2 sd;P &lt; 0.01 and P &lt; 0.05, respectively). After adjusting for differences in fat and lean mass, vertebral body and femoral neck width were no longer reduced in untreated, ERT-treated, and recovered women. Adjustment for body composition had little effect on group difference in vBMD.Bone fragility in anorexia nervosa is due to reduced bone size and reduced vBMD. Although causality cannot be inferred in cross- sectional studies, the data are consistent with the view that malnutrition may contribute to reduced bone size, whereas estrogen deficiency may reduce vBMD. The use of ERT early in disease is a reasonable component of management if the chance of recovery appears remote.