Publications by authors named "Bernard Champion"

29 Publications

  • Page 1 of 1

Macrogonadotropinoma, a venous thromboembolic event and asymptomatic extensive periventricular white matter changes in a patient with Klinefelter syndrome.

Clin Case Rep 2020 Apr 4;8(4):675-679. Epub 2020 Mar 4.

Department of Clinical Medicine Macquarie University Sydney NSW Australia.

Gonadotropinoma in Klinefelter syndrome (KS) is uncommon and may be a result of protracted stimulation of gonadotrophs from lack of androgen feedback. Associations of white matter changes and increased venous thromboembolic risk have been reported and need to be considered in patients with KS.
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http://dx.doi.org/10.1002/ccr3.2714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141726PMC
April 2020

A safety and pharmacodynamics study of temelimab, an antipathogenic human endogenous retrovirus type W envelope monoclonal antibody, in patients with type 1 diabetes.

Diabetes Obes Metab 2020 07 12;22(7):1111-1121. Epub 2020 Mar 12.

Eastern Clinical Research Unit, Eastern Health and Monash University, Box Hill, Victoria, Australia.

Aim: To report the first study of temelimab, a monoclonal antibody neutralizing the pathogenic human endogenous retrovirus type W envelope, in patients with type 1 diabetes (T1D).

Materials And Methods: This double-blind, placebo-controlled, randomized clinical trial recruited adult patients with T1D within 4 years postdiagnosis and remaining C-peptide secretion. Sixty-four patients were randomized (2:1) to monthly temelimab 6 mg/kg or placebo during 24 weeks followed by a 24-week, open-label extension, during which all patients received temelimab. The primary objective was the safety and tolerability of temelimab. The secondary objective was to assess the pharmacodynamics response such as C-peptide levels, insulin use, HbA1c, hypoglycaemia and autoantibodies.

Results: Temelimab was well tolerated without any group difference in the frequency or severity of adverse events. Concerning exploratory endpoints, there was no difference in the levels of C-peptide, insulin use or HbA1c between treatment groups at weeks 24 and 48. The frequency of hypoglycaemia events was reduced with temelimab (P = 0.0004) at week 24 and the level of anti-insulin antibodies was lower with temelimab (P < 0.01); the other autoantibodies did not differ between groups.

Conclusions: Temelimab appeared safe in patients with T1D. Pharmacodynamics signals (hypoglycaemia and anti-insulin antibodies) under temelimab were observed. Markers of β-cell functions were not modified by treatment. These results need to be further explored in younger patients with T1D with earlier disease onset.
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http://dx.doi.org/10.1111/dom.14010DOI Listing
July 2020

Clinical challenges of a co-secreting TSH/GH pituitary adenoma.

Endocrinol Diabetes Metab Case Rep 2019 Sep 17;2019. Epub 2019 Sep 17.

Department of Clinical Medicine, Level 4, Macquarie University, 2 Technology Place, Macquarie University, New South Wales, Australia.

Summary: Co-secreting thyrotropin/growth hormone (GH) pituitary adenomas are rare; their clinical presentation and long-term management are challenging. There is also a paucity of long-term data. Due to the cell of origin, these can behave as aggressive tumours. We report a case of a pituitary plurihormonal pit-1-derived macroadenoma, with overt clinical hyperthyroidism and minimal GH excess symptoms. The diagnosis was confirmed by pathology showing elevated thyroid and GH axes with failure of physiological GH suppression, elevated pituitary glycoprotein hormone alpha subunit (αGSU) and macroadenoma on imaging. Pre-operatively the patient was rendered euthyroid with carbimazole and underwent successful transphenoidal adenomectomy (TSA) with surgical cure. Histopathology displayed an elevated Ki-67 of 5.2%, necessitating long-term follow-up.

Learning Points: Thyrotropinomas are rare and likely under-diagnosed due to under-recognition of secondary hyperthyroidism. Thyrotropinomas and other plurihormonal pit-1-derived adenomas are more aggressive adenomas according to WHO guidelines. Co-secretion occurs in 30% of thyrotropinomas, requiring diligent investigation and long-term follow-up of complications.
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http://dx.doi.org/10.1530/EDM-19-0068DOI Listing
September 2019

Routine glucose assessment in the emergency department for detecting unrecognised diabetes: a cluster randomised trial.

Med J Aust 2019 11 3;211(10):454-459. Epub 2019 Nov 3.

St Vincent's Health Australia, Sydney, NSW.

Objective: 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.

Design, Setting: 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.

Participants: Patients aged 18 years or more admitted to hospital from EDs.

Intervention: Routine blood glucose assessment at control and intervention hospitals; automatic requests for glycated haemoglobin (HbA ) assessment and notification of diabetes services about patients at intervention hospitals with blood glucose levels of 14 mmol/L or more.

Main Outcome Measure: New diagnoses of diabetes and documented follow-up plans for patients with admission blood glucose levels of 14 mmol/L or more.

Results: 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.

Conclusion: Glucose and HbA screening of patients admitted to hospital from EDs does not alone increase detection of previously unidentified diabetes. Adequate resourcing and effective management pathways for patients with newly detected hyperglycaemia and diabetes are needed.

Trial Registration: Australian New Zealand Clinical Trials Registry, ACTRN12611001007921.
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http://dx.doi.org/10.5694/mja2.50394DOI Listing
November 2019

A novel CASR mutation (p.Glu757Lys) causing autosomal dominant hypocalcaemia type 1

Endocrinol Diabetes Metab Case Rep 2018 Sep 25;2018. Epub 2018 Sep 25.

University of Sydney, Sydney, New South Wales, Australia.

Autosomal dominant hypocalcaemia type 1 (ADH1) is a rare familial disorder characterised by low serum calcium and low or inappropriately normal serum PTH. It is caused by activating CASR mutations, which produces a left-shift in the set point for extracellular calcium. We describe an Australian family with a novel heterozygous missense mutation in CASR causing ADH1. Mild neuromuscular symptoms (paraesthesia, carpopedal spasm) were present in most affected individuals and required treatment with calcium and calcitriol. Basal ganglia calcification was present in three out of four affected family members. This case highlights the importance of correctly identifying genetic causes of hypocalcaemia to allow for proper management and screening of family members. Learning points: •• ADH1 is a rare cause of hypoparathyroidism due to activating CASR mutations and is the mirror image of familial hypocalciuric hypercalcaemia. •• In patients with ADH1, symptoms of hypocalcaemia may be mild or absent. Basal ganglia calcification may be present in over a third of patients. •• CASR mutation analysis is required for diagnostic confirmation and to facilitate proper management, screening and genetic counselling of affected family members. •• Treatment with calcium and activated vitamin D analogues should be reserved for symptomatic individuals due to the risk of exacerbating hypercalciuria and its associated complications.
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http://dx.doi.org/10.1530/EDM-18-0107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169543PMC
September 2018

The Effect of Cigarette Smoking during Pregnancy on Endocrine Pancreatic Function and Fetal Growth: A Pilot Study.

Front Public Health 2017 21;5:314. Epub 2017 Nov 21.

Charles Perkins Centre Nepean, University of Sydney, Sydney, NSW, Australia.

Introduction: Cigarette smoking in pregnancy is a common cause of fetal growth restriction. We aimed to investigate endocrine pancreatic function of mother-infant dyads in relation to cigarette smoking, as a possible mechanism for the poor fetal growth.

Methods: Prospective study of smoking mothers (10 cigarettes or more per day, self-reported to the midwife) and non-smoker control mothers during their first pregnancy. Insulin, glucose, C-peptide, HbA1C, fructosamine, prolactin, serotonin, and cortisol were measured in maternal blood at 24-26 weeks and in umbilical cord blood at birth. Cotinine was also measured in cord blood.

Results: Of 37 smokers and 36 non-smokers recruited, cord blood was obtainable from 38 babies (19 in each group). cigarette exposure was associated with lower birthweight (3,035 ± 490 versus 3,405 ± 598 g,  = 0.005), with linear modeling of the smoking cohort showing a 41 g reduction for every increase of one cigarette smoked per day (95% CI -71 to -11 g,  = 0.010). There were no differences between groups in indices of maternal or perinatal endocrine pancreatic dysfunction. Heavier smoking independently correlated with higher maternal fasting levels of glucose ( = 0.044) and C-peptide ( = 0.011). We did not observe any significant associations between the daily number of cigarettes and any of the cord blood parameters. We also looked for differences between cohorts based on infant gender. Serotonin levels were higher in smoking mothers with male fetuses ( = 0.01 to  = 0.004).

Conclusion: Endocrine pancreatic dysfunction does not appear to be a major contributing factor to nicotine-associated fetal growth restriction. The higher serotonin levels in smoking mothers carrying male infants is of uncertain significance but could be a manifestation of gender differences in susceptibility to the long-term effects of cigarette smoking.
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http://dx.doi.org/10.3389/fpubh.2017.00314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702296PMC
November 2017

Stimulants for the Control of Hedonic Appetite.

Front Pharmacol 2016 25;7:105. Epub 2016 Apr 25.

Charles Perkins Centre Nepean, The University of Sydney Penrith, NSW, Australia.

The focus of this paper is treatment of obesity in relation to the management of hedonic appetite. Obesity is a complex condition which may be potentiated by excessive reward seeking in combination with executive functioning deficits that impair cognitive control of behavior. Stimulant medications address both reward deficiency and enhance motivation, as well as suppressing appetite. They have long been recognized to be effective for treating obesity. However, stimulants can be abused for their euphoric effect. They induce euphoria via the same neural pathway that underlies their therapeutic effect in obesity. For this reason they have generally not been endorsed for use in obesity. Among the stimulants, only phentermine (either alone or in combination with topiramate) and bupropion (which has stimulant-like properties and is used in combination with naltrexone), are approved by the United States Food and Drug Administration (FDA) for obesity, although dexamphetamine and methylpenidate are approved and widely used for treating attention deficit hyperactivity disorder (ADHD) in adults and children. Experience gained over many years in the treatment of ADHD demonstrates that with careful dose titration, stimulants can be used safely. In obesity, improvement in mood and executive functioning could assist with the lifestyle changes necessary for weight control, acting synergistically with appetite suppression. The obesity crisis has reached the stage that strong consideration should be given to adequate utilization of this effective and inexpensive class of drug.
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http://dx.doi.org/10.3389/fphar.2016.00105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843092PMC
May 2016

Relationship between Clinical and Immunological Features of Thyroid Autoimmunity and Ophthalmopathy during Pregnancy.

J Thyroid Res 2015 21;2015:698470. Epub 2015 Dec 21.

Department of Medicine, Nepean Clinical School, The University of Sydney, Penrith, NSW 2751, Australia.

Problem. Clinical features of Graves' hyperthyroidism (GH) generally improve during pregnancy and rebound in the postpartum period. It is unclear whether the ophthalmopathy that is associated with GH and, less often, Hashimoto's thyroiditis (HT) changes in parallel with the thyroid associated antibody reactions and clinical features or runs a different course. Method of Study. We retrospectively studied 19 patients with autoimmune thyroid disease over 22 pregnancies: 9 pregnancies with GH and 13 with HT. Ophthalmopathy was defined by NOSPECS class. Results. Thyroid peroxidase (TPO) and thyroglobulin (Tg) antibody titres decreased during pregnancy and rose in the postpartum period. During pregnancy, 5 patients with GH and 4 patients with HT developed mild ophthalmopathy and two patients with GH and HT developed new upper eyelid retraction (UER). In the postpartum period, eye scores improved in 3 patients with GH and 3 with HT, remained stable in two and 5 patients, respectively, and worsened in 2 patients with GH and one with HT. Conclusions. In patients with mild to moderate eye signs associated with GH and HT, the orbital and thyroid reactions ran different courses during pregnancy. Since no patient had severe ophthalmopathy, we cannot draw definitive conclusions from this preliminary study.
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http://dx.doi.org/10.1155/2015/698470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4698935PMC
January 2016

Does autoimmunity against thyroglobulin play a role in the pathogenesis of Graves' ophthalmopathy: a review.

Clin Ophthalmol 2015 3;9:2271-6. Epub 2015 Dec 3.

Department of Medicine, Nepean Clinical School, Nepean Hospital, The University of Sydney, Sydney, NSW, Australia.

While most authors believe that autoimmunity against the TSH receptor expressed in the orbital connective tissue cells is the main reaction that leads to the development of ophthalmopathy in patients with Graves' hyperthyroidism, an older hypothesis that deserves fresh consideration is based on the notion that thyroglobulin (Tg) in the thyroid gland passes in a retrograde fashion to the orbit where it is recognized by Tg autoantibodies, leading to inflammation. Here, we review new evidence that supports a role of Tg and propose a new hypothesis based on the notion that Tg is targeted in the orbit leading to a complex cascade of reactions that leads to Graves' ophthalmopathy.
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http://dx.doi.org/10.2147/OPTH.S88444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4671807PMC
December 2015

Novel single-nucleotide polymorphisms in the calsequestrin-1 gene are associated with Graves' ophthalmopathy and Hashimoto's thyroiditis.

Clin Ophthalmol 2015 18;9:1731-40. Epub 2015 Sep 18.

Thyroid Research Laboratory, Sydney Medical School - Nepean Clinical School, The University of Sydney, Kingswood, NSW, Australia ; Nepean Blue Mountains Local Health District, Nepean Hospital, Kingswood, NSW, Australia.

Background: The eye disorder associated with Graves' disease, called Graves' ophthalmopathy (GO), greatly reduces the quality of life in affected patients. Expression of the calsequestrin (CASQ1) protein in thyroid tissue may be the trigger for the development of eye muscle damage in patients with GO. We determined the prevalence of rs74123279, rs3747673, and rs2275703 single-nucleotide polymorphism (SNPs) in patients with autoimmune thyroid disorders, GO, Graves' hyperthyroidism (GH), or Hashimoto's thyroiditis (HT) and control subjects with no personal or family history of autoimmune thyroid disorders. Furthermore, we measured the concentration of the CASQ1 protein in normal and Graves' thyroid tissue, correlating levels with parameters of the eye signs, CASQ1 antibody levels, and the CASQ1 gene polymorphism rs74123279 and rs2275703.

Methods: High-quality genomic DNA was isolated from fresh blood samples, assayed for identification of rs74123279, rs3747673, and rs2275703 SNPs in CASQ1 gene by MassARRAY SNP analysis using iPLEX technology of SEQUENOM.

Results: DNA samples from 300 patients and 106 control subjects (100 males, 306 females) with GO (n=74), GH (n=130), HT (n=96) and control subjects (n=106) were genotyped for the SNPs rs74123279, rs3747673 (n=405), and rs2275703 (n=407). The SNP rs74123279, rs3747673, and rs2275703 were identified as 1) common homozygous or wild type, 2) heterozygote, and 3) rare homozygous. Minor allele frequency for rs74123279, rs3747763, and rs2275703 were 21%, 40%, and 44%, respectively. Multiple comparisons of genotype frequency for rs74123279, rs3747763, and rs2275703 in the GO, GH, HT, and control groups showed P=0.06, 0.641, and 0.189, respectively. These results were substantiated by multiple comparison of alleles frequency for rs74123279, rs3838216, rs3747763, and rs2275703 in the GO, GH, HT, and control groups showed, P=0.36, 0.008, 0.66, and 0.05, respectively. Pairwise analysis of alleles frequency distribution in patients with GO showed significant probability for rs2275703, P=0.008.

Conclusion: Based on their evolutionary conservation and their significant prevalence, we suggest that CASQ1 gene SNPs rs74123279, rs3838216, and rs2275703 may be considered as genetic markers for GO.
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http://dx.doi.org/10.2147/OPTH.S87972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4590686PMC
October 2015

Piloting a new approach to the treatment of obesity using dexamphetamine.

Front Endocrinol (Lausanne) 2015 9;6:14. Epub 2015 Feb 9.

Sydney Medical School Nepean, University of Sydney , Penrith, NSW , Australia.

Background And Aims: There is a clear need for a new approach to the treatment of obesity, which is inexpensive and is effective for establishing lifestyle change. We conducted a pilot study to evaluate whether dexamphetamine can be used safely, combined with diet and exercise, for treating obesity. Our ultimate aim is to develop a 6-month treatment program for establishing the lifestyle changes necessary for weight control, utilizing dexamphetamine for its psychotropic effect on motivation. We viewed the anorexigenic effect as an additional advantage for promoting initial weight loss.

Methods: Obese adults were treated with dexamphetamine for 6 months (maximum of 30 mg twice daily), diet, and exercise. Weight, electrocardiogram, echocardiogram, and blood pressure were monitored.

Results: Twelve out of 14 completed 6 months treatment. Weight loss by intention to treat was 10.6 kg (95% CI 5.8-15.5, p < 0.001). The mean weight gain in the 6 months after ceasing dexamphetamine was 4.5 kg (95% CI 1.9-7.2, p = 0.003), leaving a mean weight loss at 12 months from baseline of 7.0 kg (95% CI -13.4 to -0.6, p = 0.03). All reported favorable increases in energy and alertness. Dose-limiting symptoms were mood changes (2) and insomnia (2). None had drug craving on ceasing dexamphetamine, and there were no cardiac complications. Among the seven women, there was a significant correlation for those who lost most weight on treatment to have the least regain in the following 6 months (r = 0.88, p = 0.009).

Conclusion: Our treatment with dexamphetamine, diet, and exercise was well tolerated and effective for initial weight loss. Future research will focus on identifying baseline predictive variables associated with long-term weight control.
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http://dx.doi.org/10.3389/fendo.2015.00014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4321610PMC
February 2015

Diabetic ketoacidosis due to fulminant type 1 diabetes: A rare subtype of type 1 diabetes leading to unusual sequelae.

J Intensive Care Soc 2015 Feb 10;16(1):64-70. Epub 2014 Dec 10.

Sydney Medical School, Sydney, NSW, Australia.

Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes (T1D), which without treatment leads to death. Fulminant type 1 diabetes (FT1D) is a subtype characterised by a markedly rapid and almost complete destruction of pancreatic β-cells, with acute onset leading to severe metabolic derangement and commonly ICU admission. We present a case of an 18-year-old male presenting with FT1D with two rare complications of pneumomediastinum and stress-induced cardiomyopathy (SIC) with significant myocardial necrosis. We also discuss the aetiology of the pneumomediastinum; the latest thoughts on SIC: moving beyond the simple description of 'Takotsubo cardiomyopathy'; the role of troponins in critical illness; and genetic predisposition for DKA due to FT1D.
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http://dx.doi.org/10.1177/1751143714551249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593281PMC
February 2015

Spaced scenario demonstrations improve knowledge and confidence in pediatric acute illness management.

Front Pediatr 2014 24;2:133. Epub 2014 Nov 24.

Sydney Medical School-Nepean, The University of Sydney , Sydney, NSW , Australia.

Objectives: Nationally accredited simulation courses such as advance pediatric life support and pediatric advance life support are recommended for health care professionals (HCPs) at two yearly intervals as a minimum requirement, despite literature evidence suggesting rapid decline in knowledge shortly after course completion. The objective of this study was to evaluate an observation-based, educational intervention program aimed at improving previously acquired knowledge and confidence in managing critical illnesses.

Methods: A prospective cohort longitudinal study was conducted over a 6-month period. Participants were assessed with a knowledge based questionnaire immediately prior to and after observing 12 fortnightly critical illness scenario demonstrations (CISDs). The outcome measure was performance on questionnaires. Regression analysis was used to adjust for potential confounders. Questionnaire practice effect was evaluated on 30 independent HCPs not exposed to the CISDs.

Results: Fifty-four HCPs (40 doctors and 14 nurses) participated in the study. All participants had previously attended nationally accredited simulation courses with a mean time since last attendance of 1.8 ± 0.4 years. The median number of attendances at CISD was 6 (2-12). The mean questionnaire scores at baseline (17.2/25) were significantly lower than the mean post intervention questionnaire scores (20.3/25), p = 0.003. The HCPs self-rated confidence in managing CISD was 6.5 times higher at the end of the program in the intervention group (p = 0.002) than at baseline. There was no practice effect for questionnaires demonstrated in the independent sample.

Conclusion: The educational intervention program significantly improved the knowledge and confidence of the participants in managing pediatric critical illnesses. The CISD program provides an inexpensive, practical, and time effective method of facilitating knowledge acquisition and retention. Despite the distinctively different approach, this study has shown the effectiveness of the participant being an observer to enhance pediatric resuscitation skills.
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http://dx.doi.org/10.3389/fped.2014.00133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4241830PMC
December 2014

Gestational Diabetes Independently Increases Birth Length and Augments the Effects of Maternal BMI on Birth Weight: A Retrospective Cohort Study.

Front Pediatr 2014 17;2:112. Epub 2014 Oct 17.

Sydney Medical School - Nepean, The University of Sydney , Penrith, NSW , Australia ; Charles Perkins Centre - Nepean, The University of Sydney , Penrith, NSW , Australia.

Objective: To investigate the effect of the interaction between gestational diabetes mellitus (GDM) and maternal body mass index (BMI) on the individual neonatal growth parameters.

Design: Retrospective cohort study.

Setting: A tertiary maternity service in Sydney, Australia, between 2005 and 2009.

Population: A cohort of 8859 women.

Methods: Generalized linear models.

Main Outcome Measures: Neonatal growth parameters, represented by z-scores for infant birth weight (BW), birth length (BL), and head circumference (HC) in GDM and non-GDM groups.

Results: Only GDM alone had an independent and positive effect on BL (p = 0.02) but not on BW or HC. In addition, in pregnancies complicated with GDM, the association between maternal weight and BW was significantly stronger (p < 0.001). In combination, GDM and maternal BMI significantly affected z-score differences between BW and BL (p < 0.001), in that underweight mothers had babies that were lighter relative to their length and inversely obese mothers had babies that were heavier relative to their length.

Conclusion: GDM independently influences BL and increases the association between maternal BMI and BW. In accordance with the hypothesis of the fetal origins of health and disease, the pronounced effects of GDM on fetal growth patterns demonstrated in this study are likely to influence long-term health outcomes in children.
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http://dx.doi.org/10.3389/fped.2014.00112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4201105PMC
November 2014

Thyroid-stimulating immunoglobulins as measured in a reporter bioassay are not detected in patients with Hashimoto's thyroiditis and ophthalmopathy or isolated upper eyelid retraction.

Clin Ophthalmol 2014 9;8:2071-6. Epub 2014 Oct 9.

Department of Medicine, the University of Sydney, Penrith, NSW, Australia.

Although ophthalmopathy is mainly associated with Graves' hyperthyroidism, milder eye changes are also found in about 25% of patients with Hashimoto's thyroiditis (HT). The recent finding of negative thyrotropin receptor (TSHR) antibodies, as measured in the Thyretain™ thyroid-stimulating immunoglobulin (TSI) reporter bioassay, in patients with euthyroid Graves' disease raises the possibility that TSHR antibodies are not the cause of ophthalmopathy in all situations. Here, we have tested serum from patients with HT with and without ophthalmopathy or isolated upper eyelid retraction (UER) for TSHR antibodies, using the TSI reporter bioassay and collagen XIII as a marker of autoimmunity against the orbital fibroblast. Study groups were 23 patients with HT with ophthalmopathy, isolated UER, or both eye features and 17 patients without eye signs. Thyretain™ TSI results were expressed as a percentage of the sample-to-reference ratio, with a positive test being taken as a sample-to-reference ratio of more than 140%. Serum collagen XIII antibodies were measured in standard enzyme-linked immunosorbent assay. TSI tests were positive in 22% of patients with HT with no eye signs but in no patient with eye signs. In contrast, TSI tests were positive in 94% of patients with Graves' ophthalmopathy. Tests were negative in all normal subjects tested. Collagen XIII antibodies were detected in 83% of patients with ophthalmopathy, UER, or both eye features, but in only 30% of patients with no eye signs. Our findings suggest that TSHR antibodies do not play a major role in the pathogenesis of ophthalmopathy or isolated UER in patients with HT. Moreover, the role of TSHR antibodies in the development of ophthalmopathy in patients with Graves' disease remains to be proven. In contrast, collagen XIII antibodies appear to be a good marker of eye disease in patients with HT.
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http://dx.doi.org/10.2147/OPTH.S67098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199859PMC
October 2014

Tracing Arab-Islamic inheritance in Madagascar: study of the Y-chromosome and mitochondrial DNA in the Antemoro.

PLoS One 2013 22;8(11):e80932. Epub 2013 Nov 22.

Laboratoire d'Anthropologie Moléculaire et Imagerie de Synthèse, CNRS and Université Paul Sabatier Toulouse III, UMR5288, Toulouse, France ; Centre de recherche littéraire et historique de l'Océan Indien (CRLHOI), Département d'ethnologie, Université de La Réunion, Saint-Denis, France ; Department of Pediatrics, CHU Sainte Justine, Faculty of Medecine, University of Montreal, Quebec, Canada.

Madagascar is located at the crossroads of the Asian and African worlds and is therefore of particular interest for studies on human population migration. Within the large human diversity of the Great Island, we focused our study on a particular ethnic group, the Antemoro. Their culture presents an important Arab-Islamic influence, but the question of an Arab biological inheritance remains unresolved. We analyzed paternal (n=129) and maternal (n=135) lineages of this ethnic group. Although the majority of Antemoro genetic ancestry comes from sub-Saharan African and Southeast Asian gene pools, we observed in their paternal lineages two specific haplogroups (J1 and T1) linked to Middle Eastern origins. This inheritance was restricted to some Antemoro sub-groups. Statistical analyses tended to confirm significant Middle Eastern genetic contribution. This study gives a new perspective to the large human genetic diversity in Madagascar.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0080932PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3838347PMC
December 2014

Eye findings and immunological markers in probands and their euthyroid relatives from a single family with multiple cases of thyroid autoimmunity.

Thyroid Res 2012 Jun 28;5(1). Epub 2012 Jun 28.

The Department of Medicine, The University of Sydney, Nepean Hospital, PO Box 63, Penrith, NSW 2751, Australia.

Background: Ophthalmopathy is a common manifestation of Graves' disease (GD) occurring in up to 50% of patients. Mild eye signs are also common in patients with Hashimoto's thyroiditis. Whilst a genetic predisposition to GD has been demonstrated this is not the case for the ophthalmopathy which often runs a separate course.

Objective: We determined the prevalences of eye and eyelid signs and positive thyroid and orbital antibody tests in first and second degree relatives from a single family with multiple cases of Graves' disease, ophthalmopathy and Hashimoto's thyroiditis.

Design: The study cohort comprised 16 subjects from the same family, 4 probands namely, 3 with GD and one with Hashimoto's thyroiditis and hypothyroidism and 12 of their euthyroid first or second degree relatives. We measured antibodies against calsequestrin (CASQ1) and collagen XIII in an enzyme-linked-immunosorbent assays and TSH-Receptor (TSH-R) antibodies as i) TSH-R binding inhibiting immunoglobulin (TBII) and ii) thyroid stimulating immunoglobulin (TSI). Eye signs were classified and quantified using the clinical activity score (CAS), NOSPECS classes, Nunery types 1 and 2 and the margin-reflex-distance (MRD) as a measure of upper eyelid retraction (UER).

Main Outcomes: Whilst significant ophthalmopathy was uncommon in the relatives, mild eye signs, in particular UER, were demonstrated in about a third of them. The presence of eye signs was moderately, but not significantly, associated with the detection of CASQ1 and collagen XIII antibodies, but not TSH-R antibodies.

Conclusion: Our study demonstrates a significant prevalence of positive orbital antibody tests and ophthalmopathy in probands with thyroid autoimmunity and their euthyroid relatives, favouring a role of genetic factors in the development of ophthalmopathy in patients with thyroid autoimmunity.
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http://dx.doi.org/10.1186/1756-6614-5-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464142PMC
June 2012

Clinical pathways: a departure from the art of medicine.

Med J Aust 2012 Feb;196:96

Sydney Medical School Nepean, University of Sydney, Sydney, NSW.

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http://dx.doi.org/10.5694/mja11.11391DOI Listing
February 2012

The use of complementary and alternative medicine among people living with diabetes in Sydney.

BMC Complement Altern Med 2012 Jan 12;12. Epub 2012 Jan 12.

Department of Medicine, University of Sydney, Nepean Hospital, Derby Street, Kingswood, 2751 Sydney, NSW, Australia.

Background: Complementary and alternative medicine (CAM) is common in patients with chronic disease such as diabetes mellitus. The primary objective of the study was to determine the overall prevalence and type of CAM use in individuals with diabetes mellitus (DM) in Western Sydney and to compare the prevalence and factors associated with CAM use with the literature.

Methods: A multicenter cross-sectional study was undertaken using a self-completed questionnaire distributed to patients with DM attending a public hospital and specialist endocrinology clinics in the region. The type of DM and pattern of CAM utilisation were analyzed.

Results: Sixty nine people responded to the questionnaire: age range of 18-75 years during a twelve week collection period. Overall, 32 respondents with diabetes were using some form of CAM, resulting in a utilisation rate of 46.3%. Twenty of the 32 CAM users used CAM specifically to treat their diabetes accounting for 28.9% of the respondent sample population. Multivitamins (40%), cinnamon, Co-enzyme q10 and prayer were the most frequently used CAM modalities. There was no significant difference between males and females, age range, income or diabetes complications between CAM and non-CAM users. (p values each > 0.05) The factor most significantly associated with CAM usage was being born overseas (p = 0.044).

Conclusions: Almost half the respondents (46.3%) used CAM: 28% used CAM specifically to treat their diabetes. Individuals born overseas were significantly more likely to use CAM than those born in Australia. Other factors such as age, gender, wealth and duration of living with diabetes were not associated with higher rate of CAM usage.
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http://dx.doi.org/10.1186/1472-6882-12-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295731PMC
January 2012

Delayed-onset hypoparathyroidism in an adolescent with chromosome 22Q11 deletion syndrome.

Endocr Pract 2011 Sep-Oct;17(5):e123-5

Department of Endocrinology, University of Sydney Nepean Clinical School, Penrith, NSW, Australia.

Objective: To describe the first case of established chromosome 22q11 deletion syndrome with late onset presentation of hypocalcemia secondary to hypoparathyroidism.

Methods: We present the history, clinical and laboratory investigations, and management of a 17-year-old adolescent boy who presented with 3 separate seizures secondary to hypocalcemia. This patient had an established diagnosis of chromosome 22q11 deletion syndrome at the time of the seizure presentations, but had previously normal calcium levels.

Results: Hypocalcemia was noted during each seizure, with corrected calcium levels ranging from 6.64 to 7.76 mg/dL (reference range, 8.52 to 10.52 mg/dL). The hypocalcemia was secondary to hypoparathyroidism, with parathyroid hormone levels < 2.75 pg/mL (reference range, 22.9 to 68.75 pg/mL). He was treated with calcitriol, 0.5 μg daily, and calcium carbonate, 2,400 mg daily, leading to normalization of serum calcium and resolution of seizures.

Conclusion: Chromosome 22q11 deletion syndrome is a relatively common genetic disorder with a wide variety of phenotypic manifestations including cardiac abnormalities, abnormal facies, thymic dysfunction, cleft palate, and hypocalcemia. This case shows that medical practitioners should be aware that hypocalcemia can present after an established diagnosis, which has implications for the management of this disorder.
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http://dx.doi.org/10.4158/EP11102.CRDOI Listing
May 2012

Bilateral adrenal haemorrhage in a critically ill patient.

Crit Care Resusc 2011 Jun;13(2):123-4

Nepean Hospital, Sydney, NSW, Australia.

Although rare, bilateral adrenal haemorrhage remains a life-threatening complication of severe infection and prolonged critical illness. A 67-year-old woman developed acute adrenal haemorrhage in the context of severe systemic infection due to diverticulitis and pericolic abscess. The prompt recognition and management of this condition was an important component of her eventual recovery.
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June 2011

Current concepts in graves' disease.

Ther Adv Endocrinol Metab 2011 Jun;2(3):135-44

Department of Medicine, University of Sydney, Sydney, Australia.

Graves' disease is the most common cause of hyperthyroidism in the developed world. It is caused by an immune defect in genetically susceptible individuals in whom the production of unique antibodies results in thyroid hormone excess and glandular hyperplasia. When unrecognized, Graves' disease impacts negatively on quality of life and poses serious risks of psychosis, tachyarrhythmia and cardiac failure. Beyond the thyroid, Graves' disease has diverse soft-tissue effects that reflect its systemic autoimmune nature. Thyroid eye disease is the most common of these manifestations and is important to recognise given its risk to vision and potential to deteriorate in response to radioactive iodine ablation. In this review we discuss the investigation and management of Graves' disease, the recent controversy regarding the hepatotoxicity of propylthiouracil and the emergence of novel small-molecule thyroid-stimulating hormone (TSH) receptor ligands as potential targets in the treatment of Graves' disease.
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http://dx.doi.org/10.1177/2042018811408488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3474632PMC
June 2011

Vildagliptin-induced acute pancreatitis.

Endocr Pract 2011 May-Jun;17(3):e48-50

Department of Medicine, Nepean Hospital, University of Sydney, Sydney, Australia.

Objective: To describe the first reported case of acute pancreatitis in a patient receiving vildagliptin.

Methods: We present the clinical, biochemical, and radiographic findings of the study patient.

Results: A 61-year-old woman who presented with severe abdominal pain was found to have acute pancreatitis. This occurred 5 weeks after the commencement of vildagliptin, a dipeptidyl-peptidase 4 inhibitor, for the treatment of type 2 diabetes mellitus. The patient's pancreatic enzymes were elevated (amylase, 1205 U/L; lipase, 8846 U/L), and abdominal computed tomography demonstrated diffuse pancreatic swelling, cyst formation, and necrosis in the body of the pancreas. In the absence of an identifiable cause for the patient's pancreatitis, vildagliptin was considered a potential trigger. The patient recovered after vildagliptin therapy was ceased.

Conclusions: Although incretin-based therapy effectively treats type 2 diabetes mellitus, emerging reports of acute pancreatitis in patients receiving sitagliptin and exenatide have prompted the US Food and Drug Administration to issue an alert on these drugs. This appears to be the first reported case of acute pancreatitis in a patient receiving vildagliptin, and it supports the possibility that acute pancreatitis may be a rare effect of incretin-based therapy.
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http://dx.doi.org/10.4158/EP10383.CRDOI Listing
November 2011

Riedel thyroiditis demonstrated on gallium scintigraphy.

Clin Nucl Med 2010 Aug;35(8):614-7

Department of Nuclear Medicine, Nepean Hospital, Penrith NSW, Australia.

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http://dx.doi.org/10.1097/RLU.0b013e3181e4da47DOI Listing
August 2010

Association between radioiodine therapy for Graves' hyperthyroidism and thyroid-associated ophthalmopathy.

Int Ophthalmol 2010 Aug 20;30(4):397-405. Epub 2010 Apr 20.

Department of Clinical & Biomedical Sciences, Barwon Health, The University of Melbourne, Ryrie Street, PO Box 281, Geelong, VIC, 3220, Australia.

To investigate the role of radioactive iodine (RAI) in the onset and progression of thyroid-associated ophthalmopathy (TAO). Forty-six Graves' disease patients with mild or no ophthalmopathy were prospectively treated with carbimazole (CBZ) (n = 22) or RAI (n = 24). Treatment effects were evaluated clinically over 12 months, and with orbital MRI-measured extra-ocular muscle (EOM) volumes at baseline and at 6 months. The diagnosis of TAO was based on the clinical activity score (CAS) system. There were 11/22 CBZ and 10/24 RAI patients with active ophthalmopathy at baseline. Despite greater mean TSH levels post-RAI (P = 0.003), there was no increase in the likelihood of developing active ophthalmopathy (OR 0.95; 95% CI 0.56-1.61, P = 0.9) or EOM dysfunction (OR 0.52; 95% CI 0.26-1.06, P = 0.074). The increased mean palpebral aperture post-RAI (P = 0.023) and greater mean proptosis in the CBZ group (P = 0.005) were not confirmed when the absolute values of these measurements were examined. There was no association between the treatment received and MRI-measured EOM volumes. In this study, RAI therapy for Graves' disease did not increase the risk of progression or development of ophthalmopathy in patients with mild or no eye disease at baseline.
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http://dx.doi.org/10.1007/s10792-010-9368-xDOI Listing
August 2010

Management of acute osteoporotic vertebral fractures: a nonrandomized trial comparing percutaneous vertebroplasty with conservative therapy.

Am J Med 2003 Mar;114(4):257-65

Department of Endocrinology, Saint George Hospital Campus, University of New South Wales, Grey Street, NSW 2217, Sydney, Australia.

Purpose: We sought to determine whether percutaneous vertebroplasty--which involves the injection of cement to stabilize a fractured vertebral body--may be an effective treatment for vertebral fracture.

Methods: We enrolled 79 consecutive osteoporotic patients (24 men and 55 women; ages 51 to 93 years) presenting with acute vertebral fractures. Clinical characteristics and bone densitometry were measured at baseline. Pain scores (on a 0 to 25 scale) and levels of function (on a 0 to 20 scale) were recorded on presentation, at 24 hours, at 6 weeks, and 6 to 12 months after therapy.

Results: Fifty-five patients (70%) were treated by percutaneous vertebroplasty and 24 (30%) were treated by conservative therapy alone. They were followed for a mean of 215 days (range, 57 to 399 days). The baseline clinical characteristics, bone densitometry, and fracture data were similar in the two groups. Twenty-four hours after vertebroplasty, there was a 53% reduction in pain scores (from 19 to 9; P = 0.0001) and a 29% improvement in physical functioning (from 14 to 18; P = 0.0001), whereas pain scores and physical functioning remained unchanged at 24 hours in the patients treated conservatively (both P = 0.0001 compared with the changes after percutaneous vertebroplasty). Thirteen patients (24%) treated by percutaneous vertebroplasty were able to cease all analgesia after 24 hours (P = 0.0001 compared with none of the 24 patients treated conservatively). Clinical outcomes at 6 weeks and 6 to 12 months were similar in both groups.

Conclusion: When compared with conservative therapy, percutaneous vertebroplasty results in prompt pain relief and rapid rehabilitation. In experienced hands, it is a safe and effective procedure for treating acute osteoporotic vertebral compression fractures.
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http://dx.doi.org/10.1016/s0002-9343(02)01524-3DOI Listing
March 2003

Isolated fascicular oculomotor nerve palsy as the initial presentation of the antiphospholipid syndrome.

J Clin Neurosci 2002 Nov;9(6):691-4

Department of Neurology, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.

This case report describes a 24-year-old female who presented with sudden onset of painless diplopia and ptosis in her left eye. Examination identified an isolated incomplete pupil-sparing left oculomotor nerve palsy. Magnetic resonance imaging demonstrated focal hyperintensity in the left midbrain with infarction suggested by diffusion-weighted imaging. A diagnosis of primary antiphospholipid syndrome was made with the demonstration of a positive lupus anticoagulant. Other autoimmune markers were present on initial assessment, but did not fulfil diagnostic criteria for systemic lupus erythematosus. Anticoagulation with warfarin was commenced, with gradual resolution of neurological deficits. This case illustrates an unusual initial manifestation of primary antiphospholipid syndrome causing midbrain stroke in a young woman.
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http://dx.doi.org/10.1054/jocn.2002.1113DOI Listing
November 2002