ORCID Profile
0000-0002-7732-2206
Current Organisations
University of Sydney Sydney Medical School
,
UNSW Sydney
,
South Eastern Sydney Local Health District
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Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.BBR.2015.03.020
Abstract: Growing evidence suggests that testosterone may play a role in the pathophysiology of schizophrenia given that testosterone has been linked to cognition and negative symptoms in schizophrenia. Here, we determine the extent to which serum testosterone levels are related to neural activity in affective processing circuitry in men with schizophrenia. Functional magnetic resonance imaging was used to measure blood-oxygen-level-dependent signal changes as 32 healthy controls and 26 people with schizophrenia performed a facial emotion identification task. Whole brain analyses were performed to determine regions of differential activity between groups during processing of angry versus non-threatening faces. A follow-up ROI analysis using a regression model in a subset of 16 healthy men and 16 men with schizophrenia was used to determine the extent to which serum testosterone levels were related to neural activity. Healthy controls displayed significantly greater activation than people with schizophrenia in the left inferior frontal gyrus (IFG). There was no significant difference in circulating testosterone levels between healthy men and men with schizophrenia. Regression analyses between activation in the IFG and circulating testosterone levels revealed a significant positive correlation in men with schizophrenia (r=.63, p=.01) and no significant relationship in healthy men. This study provides the first evidence that circulating serum testosterone levels are related to IFG activation during emotion face processing in men with schizophrenia but not in healthy men, which suggests that testosterone levels modulate neural processes relevant to facial emotion processing that may interfere with social functioning in men with schizophrenia.
Publisher: Oxford University Press (OUP)
Date: 13-03-2014
Abstract: Does pre-mixing stored serum s les with assay buffer improve the reproducibility of the Beckman Gen II assay for anti-Müllerian hormone (AMH)? Pre-mixing serum s les with assay buffer is a prerequisite for reproducible measurement of AMH in serum using the Beckman Coulter Gen II assay. Discrepancies in the results obtained from AMH assays have raised doubts concerning the clinical utility of measuring AMH. S le storage conditions may be responsible for the lack of reproducibility of results obtained from the Gen II kit. This was a prospective study in which serum s les were stored at three different temperatures and assayed for AMH at times 0, 4, 8, 12, 24, 48 h and 1 or 2 weeks after collection. Volunteers (n = 28) were healthy non-pregnant and early pregnant women aged 22-41 years. Anonymized long-term stored s les (n = 42, stored at -20° for 2 weeks) from fertility clinic attendees were also included. For determining the reference range, 179 s les from healthy pregnant women presenting for first trimester screening were used. Thirty separate assays were performed by two operators using four different Gen II kit lots with both kit and in-house quality controls (QCs) included in each assay. In addition to the standard protocol, a modified protocol (pre-mixing s les with assay buffer) was used for selected s le groups. In non-pregnant women, AMH concentrations remained unchanged in serum stored for up to 8 h at room temperature, -20 and -80°C. At room temperature, levels started to rise by 24 h, increasing by up to 29% of the time 0 h value by 48 h and 26% after 1 week. Significant changes versus baseline (time 0 h) in measured AMH concentration were also observed after storage at -20 and -80°C (only at the 12 h time point). In the pregnant group, there was a 50% increase above baseline in s les stored for 48 h at room temperature. When s les were pre-mixed with assay buffer, AMH concentrations showed a consistent increase versus the standard assay in both non-pregnant (29%) and pregnant (280%) groups, regardless of storage conditions and duration, but concentrations remained constant during long-term storage (2 weeks). Stored fertility clinic patient s les also exhibited stability of AMH values after a consistent 2-fold increase following pre-mixing. Kit QCs were consistent over 30 weeks using either standard or modified protocols while the in-house pooled serum QC rose over time unless using the modified protocol. Overall, there was a 2-fold increase in medians in the pre-mixed reference range, with the biggest increase observed in the oldest age bracket (41-45 years, 3.4-fold). The cause of the observed instability of AMH in stored serum s les requires further investigation, which is outside the scope of this publication. A larger and wider population study is necessary for a more reliable and clinically relevant reference range. Our study has confirmed previous findings of lack of consistency in AMH concentrations when measured with the Gen II assay. Pre-mixing serum s les with assay buffer gave higher but also the most consistent results regardless of storage conditions therefore, we propose that all serum s les for AMH assay should be pre-mixed with assay buffer. Furthermore, clinical laboratories that offer AMH measurement as part of the assessment of endocrinopathies, such as polycystic ovary syndrome or premature ovarian failure, or for management of ovulation induction as part of assisted reproduction, must re-establish their own normal ranges using the modified method. No funding was obtained for this study. There are no conflicts of interest to declare.
Publisher: Wiley
Date: 10-1999
DOI: 10.1359/JBMR.1999.14.10.1637
Abstract: The association between vitamin D receptor gene polypmorphisms and bone mineral density is controversial. The relationship between vitamin D receptor genotype and risk of fracture is uncertain. To determine whether vitamin D receptor polymorphisms were associated with the risk of hip, vertebral, and other (nonhip, nonvertebral) fractures in elderly women, we conducted a case-cohort study within a prospective study of 9704 community-dwelling women aged 65 years and older. Vitamin D receptor allele and genotype frequencies in women who experienced first incident hip (n = 181), vertebral (n = 127), and other (n = 223) fractures were compared with those of control women selected randomly from the cohort. Average length of follow-up was 6.5, 3.7, and 5.4 years for women in hip, vertebral, and other fracture analyses, respectively. Vitamin D receptor polymorphisms were determined by polymerase chain reaction lification of genomic DNA using TaqI and ApaI restriction site endonuclease digestion. All nonvertebral fractures were confirmed by X-ray reports hip fractures were validated by review of X-ray films. Vertebral fractures were defined by morphometry using lateral spine radiography at baseline and an average of 3.7 years later. Allele or genotype frequencies did not differ between fracture cases and their respective controls. Vitamin D receptor genotype (defined by TaqI, ApaI, or the combination of TaqI and ApaI) was not significantly associated with the risk of hip, vertebral, or other fractures. For ex le, compared with the referent group of women with TT genotype, those with Tt and tt genotypes had similar age- and weight-adjusted risks of fracture at the hip (hazard ratios 0.9, 95% confidence interval [CI] 0.6-1.3, and 0.8, 95% CI 0.5-1.2, respectively), spine (odds ratios 1.1, 95% CI 0.7-1.8, and 0.7, 95% CI 0.4-1.3, respectively), or other skeletal site (hazard ratios 1.0, 95% CI 0. 7-1.4, and 1.0, 95% CI 0.7-1.5, respectively). These findings were not altered in additional analyses including those adjusted for and stratified by age, ethnic ancestry, calcaneal bone density, dietary calcium intake, use of calcium supplements, use of vitamin D supplements, and oral estrogen use. We conclude that Vitamin D receptor polymorphisms defined by TaqI and ApaI are not associated with the risk of fracture in older women. Our results suggest that determination of these vitamin D receptor polymorphisms is not a clinically useful test for the prediction of fracture risk in elderly women.
Publisher: The Endocrine Society
Date: 12-2005
DOI: 10.1210/JC.2005-1153
Abstract: Hip fracture is partially genetically determined. The present study was designed to examine the contributions of vitamin D receptor (VDR) and collagen I alpha1 (COLIA1) genotypes to the liability to hip fracture in postmenopausal women. The study was designed as a prospective population-based cohort investigation. Six hundred seventy-seven postmenopausal women of Caucasian background, aged 70 +/- 7 yr (mean +/- SD), have been followed for up to 14 yr. Sixty-nine women had sustained a hip fracture during the period. Atraumatic hip fractures were prospectively identified through radiologists' reports. Bone mineral density (BMD) at the hip and lumbar spine was measured by dual-energy x-ray absorptiometry. GENOTYPES: The TaqI and SpI COLIA1 polymorphisms of the VDR and COLIA1 genes were determined. Using the Single Nucleotide Polymorphism database, VDR TT, Tt, and tt genotypes were coded as TT, TC, and CC, whereas COLIA1 SS, Ss, and ss were coded as GG, GT, and TT. Women with VDR CC genotype (16% prevalence) and COLIA1 TT genotype (5% prevalence) had an increased risk of hip fracture [odds ratio (OR) associated with CC, 2.6 95% confidence interval (CI), 1.2-5.3 OR associated with TT, 3.8 95% CI, 1.3-10.8] after adjustment for femoral neck BMD (OR, 3.4 per SD 95% CI, 2.3-5.0) and age (OR, 1.4 per 5 yr 95% CI, 1.1-1.7). Approximately 20 and 12% of the liability to hip fracture was attributable to the presence of the CC genotype and TT genotype, respectively. The VDR CC genotype and COLIA1 TT genotype were associated with increased hip fracture risk in Caucasian women, and this association was independent of BMD and age.
Publisher: AMPCo
Date: 11-2019
DOI: 10.5694/MJA2.50394
Abstract: To determine whether routine blood glucose assessment of patients admitted to hospital from emergency departments (EDs) results in higher rates of new diagnoses of diabetes and documentation of follow-up plans. Cluster randomised trial in 18 New South Wales public district and tertiary hospitals, 31 May 2011 - 31 December 2012 outcomes follow-up to 31 March 2016. Patients aged 18 years or more admitted to hospital from EDs. Routine blood glucose assessment at control and intervention hospitals automatic requests for glycated haemoglobin (HbA New diagnoses of diabetes and documented follow-up plans for patients with admission blood glucose levels of 14 mmol/L or more. Blood glucose was measured in 133 837 patients admitted to hospital from an ED. The numbers of new diabetes diagnoses with documented follow-up plans for patients with blood glucose levels of 14 mmol/L or more were similar in intervention (83/506 patients, 16%) and control hospitals (73/278, 26% adjusted odds ratio [aOR], 0.83 95% CI 0.42-1.7 P = 0.61), as were new diabetes diagnoses with or without plans (intervention, 157/506, 31% control, 86/278, 31% aOR, 1.51 95% CI, 0.83-2.80 P = 0.18). 30-day re-admission (31% v 22% aOR, 1.34 95% CI, 0.86-2.09 P = 0.21) and post-hospital mortality rates (24% v 22% aOR, 1.07 95% CI, 0.74-1.55 P = 0.72) were also similar for patients in intervention and control hospitals. Glucose and HbA Australian New Zealand Clinical Trials Registry, ACTRN12611001007921.
Publisher: Springer Science and Business Media LLC
Date: 26-08-2021
Publisher: AMPCo
Date: 20-12-2019
DOI: 10.5694/MJA2.12058
Publisher: Springer Science and Business Media LLC
Date: 1998
Abstract: Studies of gene expression in bone have adopted a number of molecular approaches that seek to determine those cis and trans-acting factors responsible for the development and physiological regulation of this unique tissue. The majority of studies have been performed in vitro, focussing on the expression of genes such as osteocalcin, bone sialoprotein and type I collagen which demonstrate restricted or altered expression patterns in osteoblasts. These studies have demonstrated a large number of cis and trans acting factors that modulate the tissue specific and vitamin D responsive expression of these genes. These include the response elements and regions mediating basal and vitamin D dependent transcription of these genes as well as some of the transcription factors that bind to these regions and the nucleosomal organisation of these genes within a nuclear framework. In vivo studies, including the introduction of transgenes into transgenic mice, extend these in vitro observations within a physiological context. However, in part due to limitations in each approach, these in vitro and in vivo studies are yet to accurately define all the necessary cis and trans-acting factors required for tissue specific and vitamin D responsive gene expression. Advances have been made in identifying many cis-acting regions within the flanking regions of these genes that are responsible for their restricted expression patterns, but a vector incorporating all the necessary cis-acting regions capable of directing gene expression independent of integration site has not yet been described. Similarly, trans-acting factors that determine the developmental destiny of osteoblast progenitors and the restricted expression of these genes remain elusive and, despite advances in the understanding of protein-DNA interactions at vitamin D response elements contained within these genes, further intermediary factors that interact with the transcriptional machinery to modulate vitamin D responsiveness need to be identified.
Publisher: The Endocrine Society
Date: 10-1997
Abstract: Human and murine osteocalcin genes demonstrate similar cell-specific expression patterns despite significant differences in gene locus organization and sequence variations in cis-acting regulatory elements. To investigate whether differences in these regulatory regions result in an altered response to 1,25-dihydroxyvitamin D3[ 1,25-(OH)2D3] in vivo, we compared the response of the endogenous mouse osteocalcin gene to a bacterial reporter gene directed by flanking regions of the human osteocalcin gene in transgenic mice. Transgene expression colocalized with endogenous osteocalcin expression in serial sections, being detected in osteoblasts, osteocytes and hypertrophic chondrocytes. In calvarial cell culture lysates from transgenic and nontransgenic mice, the endogenous mouse osteocalcin gene did not respond to 1,25-(OH)2D3 treatment. Despite this, transgene activity was significantly increased in the same cells. Similarly, Northern blots of total cellular RNA and in situ hybridization studies of transgenic animals demonstrated a maximal increase in transgene expression at 6 h after 1,25-(OH)2D3 injection (23.6 ± 3.6-fold) with a return to levels equivalent to uninjected animals by 24 h (1.2 ± 0.1-fold). This increase in transgene expression was also observed at 6 h after 1,25-(OH)2D3 treatment in animals on a low calcium diet (25.2 ± 7.7-fold) as well as in transgenic mice fed a vitamin D-deficient diet containing strontium chloride to block endogenous 1,25-(OH)2D3 production (7.5 ± 0.9-fold). In contrast to the increased transgene expression levels, neither endogenous mouse osteocalcin mRNA levels nor serum osteocalcin levels were significantly altered after 1,25-(OH)2D3 injection in transgenic or nontransgenic mice, regardless of dietary manipulations, supporting evidence for different mechanisms regulating the response of human and mouse osteocalcin genes to 1,25-(OH)2D3. Although the cis- and trans-acting mechanisms directing cell-specific gene expression appear to be conserved in the mouse and human osteocalcin genes, responsiveness to 1,25-(OH)2D3 is not. The mouse osteocalcin genes do not respond to 1,25-(OH)2D3 treatment, but the human osteocalcin-directed transgene is markedly up-regulated under the same conditions and in the same cells. The ergent responses of these homologous genes to 1,25-(OH)2D3 are therefore likely to be due to differences in mouse and human osteocalcin-regulatory sequences rather than to variation in the complement of trans-acting factors present in mouse osteoblastic cells. Increased understanding of these murine-human differences in osteocalcin regulation may shed light on the function of osteocalcin and its regulation by vitamin D in bone physiology.
Publisher: Springer Science and Business Media LLC
Date: 05-1996
DOI: 10.1007/BF01622740
Abstract: Approximately, 70% of cervical cancer cases worldwide are attributable to HPV-16 and HPV-18, with HPV-associated cancers being the second most common infection-related cancers globally. However, there´s paucity of data about this infective agent in Central Nigeria. In a cross-sectional study, we evaluated the seroprevalence of HPV-16 immunoglobulin G (IgG) and risk determinants among women in Central Nigeria as a first step towards evaluating anti-HPV IgM antibody for active cases and determining incidence. Blood s les were collected between August 2016 and January 2018, from 400 consenting women of childbearing age (15-49 years) who completed structured questionnaires. S les were analyzed using HPV-16 specific IgG ELISA kits (Cusabio Co. Ltd, Germany). Statistical analysis was performed to determine predictors. Overall, we found that 128 (32.0%) had IgG antibody against HPV-16. Seroprevalence by age was 50.0% (15-19 years), 55.0% (20-24 years), 12.9% (25-29 years), 50.0% (30-34 years), 32.1% (35-39 years), 18.2% (40-44 years) and 19.4% (45-49 years) respectively. Factors associated with infection were age (P=0.0002 95% CI 5.06-31.51), occupation (P<0.0001 95% CI 1.4-12.6), number of sex partners (P=0.0037 95% CI 1.27-49.93), history of genital warts (P=0.0203 95% CI 1.34-9.55) and education level (P<0.0001 95% CI 3.89-60.11). In addition, forty six (11.5%) reported having the history of genital warts with 268 (67.0%) and 132 (33.0%) subjects being married and single respectively. In iduals who were either artisans or civil servants were 260 (65.0%), whereas 140 (35.0%) were students. Majority, 324 (81.0%), had either primary, secondary or tertiary education with 76 (19.0%) of the subjects having no formal education. In respect of sexual behaviour, 196 (49.0%) reported having at least two sexual partners, out of which 64 (16.0%) had three or more. These findings provide high serological evidence of exposure to HPV-16 in Central Nigeria with implications for national and regional intervention initiatives.
Publisher: The Endocrine Society
Date: 08-1981
Abstract: Mitochondrial preparations from 4 human kidneys produced 1,25-dihydroxycholecalciferol and 24,25 dihydroxycholecalciferol at rates of 0.019 - 0.114 and 0.029 - 0.164 pmol/mg/min respectively at a 25-hydroxycholecalciferol concentration of 1 mumol per litre. Mitochondria from a fifth kidney failed to produce either metabolite.
Publisher: Elsevier BV
Date: 03-2018
Publisher: Wiley
Date: 12-02-2015
DOI: 10.1111/CEN.12721
Abstract: It is unclear whether the rate of vitamin D deficiency in paediatric cancer survivors is higher than in the background population, and whether this is of pathological significance. 25OHD was measured in a previously studied group of 208 survivors (n = 108 paediatric 5-17 years, n = 99 adults 18-39 years) and compared with paediatric (5-17 years n = 132) and adult controls (25-35 years n = 1393 from the AusDiab cohort) adjusted for age and gender. Relationships with treatment factors (irradiation, bone marrow transplantation and intensity of treatment) along with overweight/obesity (defined by BMI), abdominal adiposity (waist:height ratio >0·5) and hyperinsulinism or abnormal glucose tolerance (HI/aGT) were sought. 25OHD concentrations were similar in paediatric survivors compared with controls (64·3 ± 21·6 nmol/l vs 66·3 ± 22·8 nmol/l), with no effect of age or gender. Adjusted for gender, rates of 25OHD deficiency (<50 nmol/l) were higher in adult survivors compared with AusDiab controls (42·4% vs 20·8% P < 0·001). Apart from time since diagnosis (P = 0·03), no relationship with treatment factors was detected. In multivariate regression analysis, abdominal adiposity (P = 0·001), but not overweight/obesity by BMI status nor HI/aGT, was associated with significantly lower 25OHD concentrations. Adult survivors are at increased risk of abnormalities in vitamin D compared to the background population, probably reflecting longer time since diagnosis. Like others, we have not identified any contributory treatment-related factors. Vitamin D deficiency does not appear to be associated with the development of abnormal glucose tolerance in this population.
Publisher: AMPCo
Date: 02-2012
DOI: 10.5694/MJA11.11122
Publisher: American Medical Association (AMA)
Date: 20-12-1995
Publisher: Springer Science and Business Media LLC
Date: 10-2013
Publisher: SAGE Publications
Date: 29-11-2014
Abstract: An increasing number of pregnancy complications have been ascribed or at least associated with vitamin D deficiency. Vitamin D has undergone a metamorphosis from nutrient to hormone and more recently has been recognised to have broader biological relevance. This includes potential immunogenic, oncogenic and metabolic actions. This review outlines the roles of vitamin D, the problems in accurate measurement and determining normal ranges and how this is important in an understanding of vitamin D in normal and abnormal pregnancy.
Publisher: Wiley
Date: 04-1999
Publisher: Wiley
Date: 09-2004
DOI: 10.1111/J.1445-5994.2004.00647.X
Abstract: Aims: The aim of the present study was to determine if urinary excretion of type I collagen N‐terminal telopeptides (UrNTx) and deoxypyridinoline (UrDPD) and serum levels of type I collagen C‐terminal telopeptides (SeCTx) differed in patients with rheumatoid arthritis (RA) compared with populations matched for age and gender with and without osteoarthritis (OA). The correlation of markers of bone turnover with disease activity in patients with RA or radiographic severity in patients with OA was also examined. Methods: Patients with RA aged years (men) and years (women) were identified from computer databases at two tertiary referral centres for rheumatology. Strict exclusion criteria were applied to avoid the effects of factors known to influence markers of bone turnover. Patients with RA and OA were matched for age and sex with a control population free of known arthritic disease and a population with OA. Bone markers were assayed in serum and urine. Urine markers were measured on three consecutive days and mean values used to minimize day‐to‐day variability of these analytes. Results: The level of UrNTx was elevated in patients with RA compared with normal controls and patients with OA. UrNTx and UrDPD correlated with markers of disease activity in patients with RA (erythrocyte sedimentation rate and C‐reactive protein), but not with clinical signs of inflammation (swollen and tender joint counts). Patients with OA failed to show any correlation between markers of bone turnover and radiographic severity. Conclusions: These data support a role for the use of UrNTx and UrDPD in further studies of the pathophysiology of RA and in longitudinal studies designed to modify the course of clinical disease. (Intern Med J 2004 34: 539−544)
Publisher: Wiley
Date: 29-04-2020
DOI: 10.1111/DME.14303
Publisher: Springer Science and Business Media LLC
Date: 13-04-2023
DOI: 10.1038/S41598-023-33317-6
Abstract: To examine an impact of three types of bariatric surgery compared with dietary intervention (DIET), on concurrent changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and appetite hormones over 3 years. Fifty-five adults were studied during phase of weight loss (0–12 months) and during weight stability (12–36 months) post intervention. Measurements of HOMA-IR, fasting and postprandial PYY and GLP1, adiponectin, CRP, RBP4, FGF21 hormones and dual-Xray absorptiometry were performed throughout the study. All surgical groups achieved significant reductions in HOMA-IR with greatest difference between Roux-en-Y gastric bypass and DIET (− 3.7 95% CI − 5.4, − 2.1 p = 0.001) at 12–36 months. Initial (0–12 months) HOMA-IR values were no different to DIET after adjustment for the lost weight. During 12–36 months, after controlling for treatment procedure and weight, for every twofold increase in postprandial PYY and adiponectin, HOMA-IR decreased by 0.91 (95% CI − 1.71, − 0.11 p = 0.030) and by 0.59 (95% CI − 1.10, − 0.10 p = 0.023) respectively. Initial, non-sustained changes in RBP4 and FGF21 were not associated with HOMA-IR values. While initial rapid weight loss reduces insulin resistance, the enhanced secretions of PYY and adiponectin may contribute to weight-independent improvements in HOMA-IR during weight stability. Clinical trial registration : Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12613000188730.
Publisher: Springer Science and Business Media LLC
Date: 03-05-2016
DOI: 10.1038/TP.2016.59
Abstract: Estrogen has been implicated in the development and course of schizophrenia with most evidence suggesting a neuroprotective effect. Treatment with raloxifene, a selective estrogen receptor modulator, can reduce symptom severity, improve cognition and normalize brain activity during learning in schizophrenia. People with schizophrenia are especially impaired in the identification of negative facial emotions. The present study was designed to determine the extent to which adjunctive raloxifene treatment would alter abnormal neural activity during angry facial emotion recognition in schizophrenia. Twenty people with schizophrenia (12 men, 8 women) participated in a 13-week, randomized, double-blind, placebo-controlled, crossover trial of adjunctive raloxifene treatment (120 mg per day orally) and performed a facial emotion recognition task during functional magnetic resonance imaging after each treatment phase. Two-s le t -tests in regions of interest selected a priori were performed to assess activation differences between raloxifene and placebo conditions during the recognition of angry faces. Adjunctive raloxifene significantly increased activation in the right hippoc us and left inferior frontal gyrus compared with the placebo condition (family-wise error, P 0.05). There was no significant difference in performance accuracy or reaction time between active and placebo conditions. To the best of our knowledge, this study provides the first evidence suggesting that adjunctive raloxifene treatment changes neural activity in brain regions associated with facial emotion recognition in schizophrenia. These findings support the hypothesis that estrogen plays a modifying role in schizophrenia and shows that adjunctive raloxifene treatment may reverse abnormal neural activity during facial emotion recognition, which is relevant to impaired social functioning in men and women with schizophrenia.
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.JCMS.2015.04.011
Abstract: To describe the efficacy of denosumab in the treatment of an aggressive giant cell granuloma of the mandible. Denosumab was administered to a patient with a large aggressive giant cell granuloma of the mandible resistant to standard medical therapy. The effectiveness and response was measured on the basis of patient symptoms and radiological parameters. A significant reduction in patient symptoms was reported in association with tumour regression on follow up radiographs. This report demonstrates potential use of denosumab in aggressive giant cell granulomas of the jaws that have been resistant to medical therapy.
Publisher: Wiley
Date: 03-1990
Abstract: The induction of 1-hydroxylase in alveolar macrophages by tumor necrosis factor-alpha (TNF) was examined in view of recent evidence suggesting that local production of 1,25-(OH)2D3 may play a role in the regulation of immune functions. Incubation of pulmonary alveolar macrophages from normal human subjects with recombinant TNF caused a 2- to 10-fold increase in 25-hydroxyvitamin D3-1-hydroxylase activity. The dose-response curve was linear over the range 0.05-5.0 IU/ml, and no further increase was seen at higher concentrations. The increase in 1-hydroxylase activity was present after 12 h and reached a maximum after 3 days. The effect of TNF was inhibited in a dose-dependent manner by the presence of 1,25(OH)2D3 (10(-10)-10(-8) M) in the incubation media for 5 days but was unaffected by 10(-9) M 1,25(OH)2D3 after 12 h. The enhancement of macrophage 1-hydroxylase activity by TNF was comparable to that induced by gamma interferon (IFN) but the effects of maximal doses of both agents were not additive. The presence of antibody to TNF resulted in a 76% inhibition of TNF-induced 1-hydroxylase but had no significant effect on IFN-induced 1-hydroxylase activity.
Publisher: Springer Science and Business Media LLC
Date: 24-04-2018
DOI: 10.1007/S00125-018-4615-1
Abstract: Numerous adaptations of the maternal immune system are necessary during pregnancy to maintain immunological tolerance to the semi-allogeneic fetus. Several complications of pregnancy have been associated with dysregulation of these adaptive mechanisms. While gestational diabetes mellitus (GDM) has been associated with upregulation of circulating inflammatory factors linked to innate immunity, polarisation of the adaptive immune system has not been extensively characterised in this condition. We aimed to characterise pro- and anti-inflammatory CD4 This is a prospective longitudinal case-control study of 55 women with GDM (cases) and 65 women without GDM (controls) at a tertiary maternity hospital. Quantification of proinflammatory (Th17, Th17.1, Th1) and anti-inflammatory (regulatory T cell [Treg]) CD4 Women with GDM had a significantly greater percentage of Th17 (median 2.49% [interquartile range 1.62-4.60] vs 1.85% [1.13-2.98], p = 0.012) and Th17.1 (3.06% [1.30-4.33] vs 1.55% [0.65-3.13], p = 0.006) cells compared with the control group of women without GDM. Women with GDM also had higher proinflammatory cell ratios (Th17:Treg, Th17.1:Treg and Th1:Treg) in pregnancy compared with the control group of women without GDM. In the control group, there was a statistically significant independent association between 1 h glucose levels in the GTT and Th17 cell percentages, and also between 2 h glucose levels and percentage of Th17 cells. The percentage of Th17 cells and the Th17:Treg ratio declined significantly after delivery in women with GDM, whereas this was not the case with the control group of women. Nevertheless, a milder inflammatory phenotype persisted after delivery (higher Th17:Treg ratio) in women with GDM vs women without. Dysregulation of adaptive immunity supports a novel paradigm of GDM that extends beyond hyperglycaemia and altered innate immunity.
Publisher: The Endocrine Society
Date: 23-01-2017
DOI: 10.1210/JC.2016-3282
Abstract: The contribution of insulin resistance vs adiposity to bone mineral density (BMD), bone turnover, and fractures in humans remains unclear. To evaluate BMD and bone turnover markers (BTMs) in lean (n = 18) and overweight/obese in iduals with (n = 17) and without (n = 34, insulin-sensitive [Obsensitive, n=15] or insulin-resistant [Obresistant, n=19] by homeostasis model assessment insulin resistance) diabetes mellitus. Observational study. Insulin sensitivity was assessed using the hyperinsulinemic-euglycemic cl whole body BMD and fat mass (FM) using dual energy X-ray absorptiometry and by measurement of BTMs [osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), and collagen type 1 cross-linked C-terminal telopeptide (CTx)], with the patient fasting and during cl hyperinsulinemia. Fasting BTMs correlated with glucose infusion rate/fat-free mass (GIR/FFM) and adiponectin and, inversely, with fasting insulin and visceral fat (P ≤ 0.04 for all). Obsensitive, Obresistant, and diabetic in iduals were matched by their FM percentage. Cl GIR/FFM was similar in the lean and Obsensitive subjects (P = 1) and approximately twofold greater (P < 0.001) than in the Obresistant and diabetic subjects. BMD was greater in Obresistant than in Obsensitive (P = 0.04) and lean (P = 0.001) subjects. At baseline, compared with Obsensitive and lean subjects, Obresistant and diabetic in iduals had lower OC, P1NP, and CTx levels. This reached statistical significance for Obresistant vs lean and Obresistant vs Obsensitive for both OC and CTx and for diabetic vs lean for CTx (P ≤ 0.04 for all). During hyperinsulinemia, lean in iduals suppressed CTx more than did diabetic in iduals (P = 0.03). On multiple regression analysis, visceral adiposity explained 16.7% and 19.3% of the baseline OC and CTx variability, respectively. Increased visceral adiposity and higher fasting insulin in insulin-resistant states are associated with lower fasting OC and CTx and failure to further suppress with more insulin.
Publisher: Springer Science and Business Media LLC
Date: 03-2009
DOI: 10.1007/BF03346467
Publisher: Elsevier BV
Date: 2023
Publisher: Wiley
Date: 02-2000
DOI: 10.1046/J.1365-2265.2000.00918.X
Abstract: Primary hypothyroidism can cause disturbances in normal gonadal function. The aim of this study was to investigate the relationship in men between hypogonadism and primary hypothyroidism and the extent to which free and total testosterone levels rose after introduction of replacement thyroxine. Paired study of patients in a hypothyroid and thyroxine treated state. Ten men with primary hypothyroidism. Free and total testosterone, gonadotrophin and prolactin levels before and after thyroxine replacement therapy. Low free testosterone levels (161 +/- 62 pmol/l) demonstrated at the time the men were hypothyroid rose significantly with the commencement of thyroxine replacement (315 +/- 141 pmol/l P < 0.001). Gonadotrophin levels were not elevated consistent with hypogonadotrophic hypogonadism. Hyperprolactinaemia, which can occur in primary hypothyroidism and cause hypogonadotrophic hypogonadism, was not present in the majority of these patients. However a reduction in prolactin level was evident with thyroxine replacement and a rise in free testosterone levels. This suggests an effect of hypothyroidism on gonadotrophin secretion at the level of the hypothalamus-pituitary, either directly or through modulation of prolactin secretion. Low free testosterone may also be a contributing factor to some of the symptoms and signs of hypothyroidism in men.
Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1016/J.BONE.2022.116373
Abstract: Diabetes and fractures are both associated with increased mortality, however the effect of the combination is not well-established. We examined the mortality risk following all types of fractures in type 2 diabetes (T2D). In the Dubbo Osteoporosis Epidemiology Study (1989-2017), participants were grouped according to T2D and/or incident fracture. Study outcome was all-cause mortality. First incident radiological fragility fracture and incident T2D diagnosis were time-dependent variables. Cox's proportional hazards models quantified mortality risk associated with T2D and incident fracture overall, as well as by fracture site, T2D duration and T2D medication type. In 3618 participants (62% women), 272 had baseline and 179 developed T2D over median 13.0 years (IQR 8.2-19.6). 796 women (56 with T2D) and 240 men (25 with T2D) sustained a fracture. Compared to those without T2D or fracture, mortality risk increased progressively, in T2D without fracture, then no T2D with fracture, and was highest in those with T2D with fracture (adjusted hazard ratio (aHR) (95% CI) for women 2.62 (1.75-3.93) and men 2.61 (1.42-4.81)). Within T2D participants, incident fracture was associated with increased mortality (aHR for women 1.87 (1.10-3.16) and men 2.83 (1.41-5.68)), especially following hip/vertebral fractures in men (aHR 2.97 (1.29-6.83)) and non-hip non-vertebral fractures in women (aHR 2.42 (1.24-4.75)), and in T2D duration >5 years. Any fracture in T2D conferred significant excess mortality. In iduals with T2D should be carefully monitored post-fracture, especially if T2D >5 years. Optimising fracture prevention and post-fracture management in T2D is critical and warrants further studies.
Publisher: Elsevier BV
Date: 11-2022
DOI: 10.1016/J.JAPH.2022.06.014
Abstract: Osteoporosis is a major public health concern, given that disease prevalence is expected to substantially increase due to the aging population. Community pharmacists can play a key role in the identification and management of chronic diseases. The purpose of this systematic review was to present an overview of the literature on the role of community pharmacists in providing osteoporosis interventions to patients. The secondary objective was to assess the impact of these interventions on patient outcomes. A literature search was conducted in Embase, CINAHL, Scopus, MEDLINE, and Web of Science from database inception to March 2021. The search was limited to human studies in the English language. Primary studies were included if they described or assessed a patient-directed osteoporosis intervention conducted by community pharmacists. The following data were extracted and tabulated: citation, study location, study design, subject, number of participants, nature of intervention, classification of intervention, outcome measures, measurement methods, findings, and effect. Risk of bias was assessed using the Cochrane Risk of Bias tool for randomized trials (RoB 2) and Risk of Bias in Non-randomized Studies (ROBINS-I). Twenty-one studies were included in this review. The main interventions were education, screening, and medication management. Nineteen of these studies reported patient outcomes, all yielding positive outcomes. Outcomes included increased physician follow-up, risk factor reduction, increased osteoporosis knowledge, increased medication adherence, identification of medication-related problems, and positive patient-reported experience measures (PREMs). Three studies were considered to have a moderate risk of bias, whereas the remaining 18 studies had a high risk of bias. There is some evidence that pharmacist-led osteoporosis interventions have a positive impact on patient outcomes. More high-quality studies using objective outcome measures are needed to determine whether this translates into clinical outcomes such as decreased hospitalization and fractures.
Publisher: Wiley
Date: 08-2012
Publisher: IEEE
Date: 04-2020
Publisher: Walter de Gruyter GmbH
Date: 09-2016
Abstract: A pilot study showing a decrease in androstenedione concentration in serum collected into gel-containing serum tubes (STs) triggered an investigation of the effect of serum collection tube on steroid hormone stability. In the main study, two tube types were examined: BD Vacutainer ® SST™II Advance and BD Vacutainer ® Serum Tube. Forty-seven serum s les from apparently healthy volunteers were collected and analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) for testosterone, androstenedione, 17-hydroxyprogesterone (17-OHP) (n=20) and oestradiol (n=27). Primary specimens were centrifuged once, maintained at room temperature and extracted within 2 h for day zero (d0) results. To assess stability following refrigeration (2–8 °C), aliquots were taken from the primary tube on day one (d1) and day five (d5) and analysed immediately. Differences in measurand concentration between tubes at d0 and following storage (d1 and d5) were evaluated for statistical significance. There was a progressive and statistically significant decrease in androstenedione concentration from d0 to d5 (p .001) in the SST™II tubes. In addition, there was a statistically significant reduction in testosterone, 17-OHP and oestradiol concentrations at d5 (p .01). Interestingly, oestradiol and testosterone concentrations increased with time in plain STs (p .01). The only change likely to have a clinical impact was that of androstenedione in serum gel tubes. To optimise conditions and to reduce pre-analytical error we recommend the use of plain serum collection tubes for androstenedione and rapid separation of serum from cells when oestradiol and testosterone are requested.
Publisher: Elsevier BV
Date: 03-2017
Publisher: Elsevier BV
Date: 06-1998
DOI: 10.1016/S0889-8529(05)70010-4
Abstract: In summary, the optimal model for the prevention of osteoporotic fractures includes maximization and maintenance of bone strength and minimization of trauma. Numerous determinants of each have been identified, but further work to develop preventative strategies based on these determinants remains to be undertaken. Physical activity is a determinant of peak BMD. There also is evidence that activity during growth modulates the external geometry and trabecular architecture, potentially enhancing skeletal strength, while during the adult years activity may reduce age-related bone loss. The magnitude of the effect of a 7% to 8% increase in peak BMD, if maintained through the adult years, could translate to a 1.5-fold reduction in fracture risk. Moreover, in the older population, appropriate forms of exercise could reduce the risk of falling and, thus, further reduce fracture risk. These data must be considered as preliminary in view of the paucity of long-term fracture outcome data from randomized clinical trials. However, current information suggests that the optimal form of exercise to achieve these objectives may vary through life. Vigorous physical activity (including weight-bearing, resistance, and impact components) during childhood may maximize peak BMD. This type of activity seems optimal through the young adult years, but as inevitable age-related degeneration occurs, activity modification to limit the impact component of exercise may become necessary. In the elderly, progressive strength training has been demonstrated to be a safe and effective form of exercise that reduces risk factors for falling and may also enhance BMD. In the frail elderly, activity to improve balance and confidence also may be valuable. Group activities such as Tai Chi may be cost-effective. Precise prescriptions must await the outcome of well-designed, controlled longitudinal studies that include fracture as an outcome. However, increased physical activity seems to be a sensible component of strategies to reduce osteoporotic fracture.
Publisher: Wiley
Date: 11-1994
Abstract: The vitamin D endocrine system is central to the control of bone and calcium homeostasis. The active hormonal form of vitamin D, 1,25 dihydroxyvitamin D (calcitriol), the circulating level of which is tightly regulated, acts through a specific receptor to mediate its genomic actions on almost every aspect of calcium homeostasis. Because of its transactivation function, it is possible that a small difference in vitamin D receptor level could be lified into a biologically significant alteration in physiological setpoint. The recent finding that polymorphisms in the vitamin D receptor gene are predictive of bone density (Morrison et al., Nature 367:284-287, 1994) is the first ex le of an allelic effect in such a homeostatically controlled system. This raises the possibility that such central operators may exist in other regulatory pathways, and could explain a large part of the observed "normal" population distribution that exists for all physiological parameters.
Publisher: Wiley
Date: 04-2020
DOI: 10.1002/NAU.24331
Publisher: Wiley
Date: 23-06-2020
DOI: 10.1111/HIV.12882
Publisher: The Endocrine Society
Date: 06-2015
DOI: 10.1210/JC.2014-4103
Abstract: Maternal pregnancy-associated plasma protein-A (PAPP-A) is measured at nuchal translucency scanning to assess the risk of fetal chromosomal disorders. The aim of this study was to examine whether PAPP-A might also be a predictor of gestational diabetes (GDM), type 2 diabetes (T2D), or large-for-gestational-age (LGA) births. PAPP-A levels were measured in serum from 1664 women at their 10-14-week nuchal translucency scan at a tertiary referral hospital. Maternal diabetes was categorized as T2D, "early GDM" (GDM diagnosed < 22 wk), and "late GDM" (GDM diagnosed ≥ 22 wk). The relationship between PAPP-A multiples of the median (MoM), maternal diabetes, and LGA was examined with multivariate regression models. PAPP-A MoM was significantly lower in women with T2D and women who developed GDM than in nondiabetic women. PAPP-A MoM was 41.3% lower in T2D, 22.6% lower in early GDM, and 8.6% lower in late GDM. Women in the lowest quartile of PAPP-A MoM were 2.7 times more likely to have early GDM (odds ratio [OR], 2.74 95% confidence interval [CI], 1.2-6.1) compared with the highest quartile. Birth weight had a positive linear association with PAPP-A MoM. Women in the highest PAPP-A MoM quartile were twice as likely to have an LGA baby (OR, 2.2 95% CI, 1.39-3.46 P = .0007). Routinely tested first-trimester PAPP-A is a novel biomarker for maternal diabetes and LGA. PAPP-A decreased with increasing severity of maternal diabetes. Although this cannot infer causality, low PAPP-A may help identify women at risk of GDM, and high PAPP-A may help identify pregnancies at risk of LGA.
Publisher: The Endocrine Society
Date: 09-1995
DOI: 10.1210/JCEM.80.9.7673413
Abstract: The risk of osteoporotic fracture is related to peak bone mass achieved at skeletal maturity and subsequent bone loss. Although premature menopause is a risk factor for osteoporosis, the effect of exposure to endogenous estrogen during a woman's reproductive years is poorly characterized. We analyzed the relationship between reproductive factors and estrogen exposure on bone mineral density (BMD) and incidence of atraumatic fracture in data from 1091 women (age: 70 +/- 7.2 yr mean +/- SD) participating in the Dubbo Osteoporosis Epidemiology Study. Age- and weight-adjusted BMD among women who had used estrogen replacement therapy (ERT) for more than 5 yr was higher at the lumbar spine and femoral neck by 13.7% and 10.2% (P < 0.001), respectively, compared with women who had used ERT for less than 5 yr or nonusers. Duration of exposure to estrogen (years of menstruation plus postmenopausal ERT use) was associated with higher BMD, such that BMD increased by 2-3% for every 10-yr increase in years of estrogen exposure thus women who menstruated for more than 40 yr had a 6-8% higher BMD than did women who menstruated for less than 30 yr. Higher BMD was also significantly associated with high parity, such that nulliparous women had 5-6% lower BMD than did their peers of the same age and weight. The incidence of atraumatic fractures among non-ERT users was higher than that of ERT-users [odds ratio (OR): 1.06 95% confidence interval (CI): 0.94-1.16] and was significantly lower among parous women than among nulliparous women (OR 0.94 95% CI: 0.84-0.98) in univariate analysis. Longer duration of menstruation was associated with lower fracture incidence (OR for 1 SD = 6.6 yr: 0.93 95% CI: 0.86-1.02). Moreover, when all of these factors were considered simultaneously, parity remained a significant determinant of fracture as well as femoral neck BMD. We conclude that high parity and longer duration of exposure to estrogen, either through natural menstruation or postmenopausal ERT, have protective effects on BMD and are associated with a reduced incidence of atraumatic fracture in a population-based study.
Publisher: Oxford University Press (OUP)
Date: 11-2001
Abstract: A 51 year old man presented with a two year history of gradually deteriorating vision in his left eye, accompanied by 34 kg weight gain, easy bruising, and hypertension which was relatively resistant to conventional treatment. The patient denied any history of headaches. On examination, his general appearance was as shown (fig 1). On ocular examination his visual acuity was 6/6 in the right and 6/12 in the left eye. A left relative afferent pupillary defect was present and fundoscopically there was left optic nerve atrophy. Numerous investigations were performed, including Humphrey's field analysis (fig 2), and a cerebral magnetic resonance imaging (MRI) scan (fig 3). Eye positions on left lateral gaze were as shown (fig 4).
Publisher: BMJ
Date: 02-1998
DOI: 10.1136/ARD.57.2.94
Abstract: To describe the relation between spinal degenerative disease, allelic variation in the vitamin D receptor gene, and lifestyle factors in a population-based association study. Random population-based s le of 110 men and 172 women over 60 years of age participating in the Dubbo Osteoporosis Epidemiology Study who had spinal radiographs (performed according to a standardised approach), assessment of lifestyle factors, bone densitometry as well as blood taken for genotyping. Spinal degenerative disease of varying severity was common in this s le. Multivariate analysis of genetic and lifestyle factors simultaneously strengthened the statistical significance of each indicating the presence of additive gene environment interaction. Allelic variation in the vitamin D receptor gene was associated with severity of osteophytosis (adjusted OR "TT" v "tt" 0.41, 95% CI 0.17, 0.97), presence of disc narrowing (adjusted OR "TT" v "tt" 0.45, 95% CI 0.20, 0.99) and weakly with presence of osteophytosis (adjusted OR "TT" v "tt" 0.47, 95% CI 0.19, 1.16) but not with severity of disc narrowing (OR "TT" v "tt" 1.05, 95% CI 0.40, 2.72) or apophyseal arthritis (OR "TT" v "tt" 0.63, 95% CI 0.24, 1.59). Adjustment for femoral neck bone density did not change these findings suggesting that the association is not mediated through bone density. Presence and severity of spinal degenerative disease increased with age at all sites. Current smoking increased both the presence (adjusted OR 9.70, 95% CI 2.08, 45.1) and severity (adjusted OR 2.91, 95% CI 1.16, 9.03) of spinal osteophytosis with intermediate values for past smokers. Severity of osteophytosis was also independently associated with body mass index and quadriceps strength consistent with a contributory effect of physical loading. In this elderly s le, both genetic and lifestyle factors were associated with the presence and severity of spinal degenerative disease. There were site specific differences in associations at the spine, which may be because of misclassification of disease status or may indicate possible environmental and genetic differences in the pathophysiology of spinal degenerative disease. Further studies are required to confirm these findings in different population s les and to further explore potential aetiological mechanisms particularly gene environment interaction.
Publisher: Wiley
Date: 19-03-2023
DOI: 10.1002/DMRR.3631
Abstract: Fracture risk is elevated in some type 2 diabetes patients. Bone fragility may be associated with more clinically severe type 2 diabetes, although prospective studies are lacking. It is unknown which diabetes‐related characteristics are independently associated with fracture risk. In this post‐hoc analysis of fracture data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial (ISRCTN#64783481), we hypothesised that diabetic microvascular complications are associated with bone fragility. The FIELD trial randomly assigned 9795 type 2 diabetes participants (aged 50–75 years) to receive oral co‐micronised fenofibrate 200 mg ( n = 4895) or placebo ( n = 4900) daily for a median of 5 years. We used Cox proportional hazards models to identify baseline sex‐specific diabetes‐related parameters independently associated with incident fractures. Over 49,470 person‐years, 137/6138 men experienced 141 fractures and 143/3657 women experienced 145 fractures incidence rates for the first fracture of 4∙4 (95% CI 3∙8–5∙2) and 7∙7 per 1000 person‐years (95% CI 6∙5–9∙1), respectively. Fenofibrate had no effect on fracture outcomes. In men, baseline macrovascular disease (HR 1∙52, 95% CI 1∙05–2∙21, p = 0∙03), insulin use (HR 1∙62, HR 1∙03–2∙55, p = 0∙03), and HDL‐cholesterol (HR 2∙20, 95% CI 1∙11–4∙36, p = 0∙02) were independently associated with fracture. In women, independent risk factors included baseline peripheral neuropathy (HR 2∙04, 95% CI 1∙16–3∙59, p = 0∙01) and insulin use (HR 1∙55, 95% CI 1∙02–2∙33, p = 0∙04). Insulin use and sex‐specific complications (in men, macrovascular disease in women, neuropathy) are independently associated with fragility fractures in adults with type 2 diabetes.
Publisher: Springer Science and Business Media LLC
Date: 2004
No related grants have been discovered for chris white.