66 results on '"David S. Celermajer"'
Search Results
2. β3 adrenergic agonism: A novel pathway which improves right ventricular‐pulmonary arterial hemodynamics in pulmonary arterial hypertension
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Keyvan Karimi Galougahi, Yunjia Zhang, Vivian Kienzle, Chia‐Chi Liu, Lake‐Ee Quek, Sanjay Patel, Edmund Lau, Rachael L. Cordina, Gemma A. Figtree, and David S. Celermajer
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endothelial nitric oxide synthase ,pulmonary arterial hypertension ,redox signaling ,right ventricular hemodynamics ,β3 adrenergic receptors ,Physiology ,QP1-981 - Abstract
Abstract Efficacy of therapies that target the downstream nitric oxide (NO) pathway in pulmonary arterial hypertension (PAH) depends on the bioavailability of NO. Reduced NO level in PAH is secondary to “uncoupling” of endothelial nitric oxide synthase (eNOS). Stimulation of β3 adrenergic receptors (β3 ARs) may lead to the recoupling of NOS and therefore be beneficial in PAH. We aimed to examine the efficacy of β3 AR agonism as a novel pathway in experimental PAH. In hypoxia (5 weeks) and Sugen hypoxia (hypoxia for 5 weeks + SU5416 injection) models of PAH, we examined the effects of the selective β3 AR agonist CL316243. We measured echocardiographic indices and invasive right ventricular (RV)–pulmonary arterial (PA) hemodynamics and compared CL316243 with riociguat and sildenafil. We assessed treatment effects on RV–PA remodeling, oxidative stress, and eNOS glutathionylation, an oxidative modification that uncouples eNOS. Compared with normoxic mice, RV systolic pressure was increased in the control hypoxic mice (p
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- 2023
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3. Moderate‐ and High‐Intensity Exercise Improves Lipoprotein Profile and Cholesterol Efflux Capacity in Healthy Young Men
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Kelly M. Stanton, Vivian Kienzle, Donna Lee M. Dinnes, Irina Kotchetkov, Wendy Jessup, Leonard Kritharides, David S. Celermajer, and Kerry‐Anne Rye
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ATP‐binding cassette transporters ,cholesterol ,cholesterol efflux capacity ,exercise ,HDL‐C ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Exercise is associated with a reduced risk of cardiovascular disease. Increased high‐density lipoprotein cholesterol (HDL‐C) levels are thought to contribute to these benefits, but much of the research in this area has been limited by lack of well‐controlled subject selection and exercise interventions. We sought to study the effect of moderate and high‐intensity exercise on HDL function, lipid/lipoprotein profile, and other cardiometabolic parameters in a homogeneous population where exercise, daily routine, sleep patterns, and living conditions were carefully controlled. Methods and Results Male Army recruits (n=115, age 22±0.3 years) completed a 12‐week moderate‐intensity exercise program. A subset of 51 subsequently completed a 15‐week high‐intensity exercise program. Fitness increased and body fat decreased after moderate‐ and high‐intensity exercise (P
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- 2022
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4. Impact of Fontan Fenestration on Long‐Term Outcomes: A Propensity Score–Matched Analysis
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Michael Daley, Edward Buratto, Gregory King, Leeanne Grigg, Ajay Iyengar, Nelson Alphonso, Andrew Bullock, David S. Celermajer, Julian Ayer, Terry Robertson, Yves d’Udekem, and Igor E. Konstantinov
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fenestration ,risk factor ,survival ,thromboembolism ,univentricular ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background The long‐term impact of fenestration at the time of Fontan operation remains unclear. We aimed to review the early and long‐term impact of Fontan fenestration in the Australia and New Zealand cohort. Methods and Results We reviewed 1443 patients (621 fenestrated, 822 nonfenestrated) from the Australia and New Zealand Fontan registry. Data were collected on preoperative demographics, operative details, and follow‐up. Propensity‐score matching was performed to account for the various preoperative and operative differences and risk factors. Primary outcomes were survival and freedom from failure. Median follow‐up was 10.6 years. After propensity‐score matching (407 matched pairs), there was no difference in survival (87% versus 90% at 20 years; P=0.16) or freedom from failure (73% versus 80% at 20 years; P=0.10) between patients with and without fenestration, respectively. Although patients with fenestration had longer bypass and cross‐clamp times (P
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- 2022
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5. Prevalence and Outcomes of Low‐Gradient Severe Aortic Stenosis—From the National Echo Database of Australia
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Afik D. Snir, Martin K. Ng, Geoff Strange, David Playford, Simon Stewart, and David S. Celermajer
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aortic stenosis ,low flow, low gradient ,low gradient ,normal flow, low gradient ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background The prevalence and outcomes of the different subtypes of severe low‐gradient aortic stenosis (AS) in routine clinical cardiology practice have not been well characterized. Methods and Results Data were derived from the National Echocardiography Database of Australia. Of 192 060 adults (aged 62.8±17.8 [mean±SD] years) with native aortic valve profiling between 2000 and 2019, 12 013 (6.3%) had severe AS. Of these, 5601 patients (47%) had high‐gradient and 6412 patients (53%) had low‐gradient severe AS. The stroke volume index was documented in 2741 (42.7%) patients with low gradient; 1750 patients (64%) with low flow, low gradient (LFLG); and 991 patients with normal flow, low gradient. Of the patients with LFLG, 1570 (89.7%) had left ventricular ejection fraction recorded; 959 (61%) had paradoxical LFLG (preserved left ventricular ejection fraction), and 611 (39%) had classical LFLG (reduced left ventricular ejection fraction). All‐cause and cardiovascular‐related mortality were assessed in the 8162 patients with classifiable severe AS subtype during a mean±SD follow‐up of 88±45 months. Actual 1‐year and 5‐year all‐cause mortality rates varied across these groups and were 15.8% and 49.2% among patients with high‐gradient severe AS, 11.6% and 53.6% in patients with normal‐flow, low‐gradient severe AS, 16.9% and 58.8% in patients with paradoxical LFLG severe AS, and 30.5% and 72.9% in patients with classical LFLG severe AS. Compared with patients with high‐gradient severe AS, the 5‐year age‐adjusted and sex‐adjusted mortality risk hazard ratios were 0.94 (95% CI, 0.85–1.03) in patients with normal‐flow, low‐gradient severe AS; 1.01 (95% CI, 0.92–1.12) in patients with paradoxical LFLG severe AS; and 1.65 (95% CI, 1.48–1.84) in patients with classical LFLG severe AS. Conclusions Approximately half of those patients with echocardiographic features of severe AS in routine clinical practice have low‐gradient hemodynamics, which is associated with long‐term mortality comparable with or worse than high‐gradient severe AS. The poorest survival was associated with classical LFLG severe AS.
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- 2021
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6. Characteristics of Bicuspid Aortic Valve Disease and Stenosis: The National Echo Database of Australia
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Michelle S. Lim, Geoff Strange, David Playford, Simon Stewart, and David S. Celermajer
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aortic stenosis ,cardiac ultrasound ,mortality ,regurgitation ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Bicuspid aortic valve (BAV) is the most common congenital heart disease in adults but is clinically heterogeneous. We aimed to describe the echocardiographic characteristics of BAV and compare patients with BAV with moderate‐to‐severe aortic stenosis (AS) with those with tricuspid aortic valve (TAV) stenosis. Methods and Results Using the National Echo Database of Australia, patients in whom BAV was identified were studied. Those with moderate‐to‐severe AS (mean gradient >20 mm Hg [BAV‐AS]) were compared with those with TAV and moderate‐to‐severe AS (TAV‐AS). Of 264 159 adults whose aortic valve morphology was specified, 4783 (1.8%) had confirmed BAV (aged 49.6±17.4 years, 69% men). Of these, 42% had no AS, and 46% had no aortic regurgitation. Moderate‐to‐severe AS was detected in a greater proportion of patients with BAV with a recorded mean gradient (n=1112, 34%) compared with those with TAV (n=4377, 4%; P
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- 2021
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7. Body Composition in Young Adults Living With a Fontan Circulation: The Myopenic Profile
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Derek Tran, Paolo D'Ambrosio, Charlotte E. Verrall, Chantal Attard, Julie Briody, Mario D'Souza, Maria Fiatarone Singh, Julian Ayer, Yves d'Udekem, Stephen Twigg, Glen M. Davis, David S. Celermajer, and Rachael Cordina
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congenital heart disease ,exercise capacity ,muscle wasting ,obesity ,single ventricle ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background We sought to characterize body composition abnormalities in young patients living with a Fontan circulation and explore potential pathophysiologic associations. Methods and Results Twenty‐eight patients with a Fontan circulation were prospectively recruited in this cross‐sectional study. Participants underwent cardiopulmonary exercise testing, dual‐energy X‐ray absorptiometry, echocardiography, and biochemical assessment. Mean age was 26±7 years. Skeletal muscle mass, estimated by appendicular lean mass index Z score, was reduced compared with reference data (−1.49±1.10, P
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- 2020
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8. Health‐Related Quality of Life in Children, Adolescents, and Adults With a Fontan Circulation: A Meta‐Analysis
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Kate H. Marshall, Yves D'Udekem, Gary F. Sholler, Alexander R. Opotowsky, Daniel S. J. Costa, Louise Sharpe, David S. Celermajer, David S. Winlaw, Jane W. Newburger, and Nadine A. Kasparian
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chronic illness ,congenital heart disease ,Fontan circulation ,health‐related quality of life ,mental health ,psychological stress ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background People with a Fontan circulation experience a range of physical, psychosocial and neurodevelopmental challenges alongside, or caused by, their cardiac condition, with significant consequences for health‐related quality of life (HRQOL). We meta‐analyzed HRQOL outcomes reported by people with a Fontan circulation or their proxies and evaluated predictors of poorer HRQOL. Methods and Results Six electronic databases were searched for peer‐reviewed, English‐language articles published before March 2019. Standardized mean differences (SMD) were calculated using fixed and random‐effects models. Fifty articles reporting on 29 unique studies capturing HRQOL outcomes for 2793 people with a Fontan circulation and 1437 parent‐proxies were analyzed. HRQOL was lower in individuals with a Fontan circulation compared with healthy referents or normative samples (SMD, −0.92; 95% CI, −1.36 to −0.48; P
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- 2020
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9. Change in ejection fraction and <scp>long‐term</scp> mortality in adults referred for echocardiography
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David S. Celermajer, Simon Stewart, Jim Codde, David L. Prior, Geoff Strange, Yih-Kai Chan, Gregory M. Scalia, Max Bulsara, and David Playford
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Adult ,Male ,Cardiac function curve ,medicine.medical_specialty ,030204 cardiovascular system & hematology ,Ventricular Function, Left ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Interquartile range ,Internal medicine ,medicine ,Humans ,echocardiography ,Clinical significance ,cardiovascular diseases ,Heart Failure ,Ejection fraction ,business.industry ,Stroke Volume ,left ventricular ejection fraction ,Stroke volume ,Prognosis ,medicine.disease ,mortality ,Heart failure ,Cohort ,cardiovascular system ,Cardiology ,Female ,cardiac function ,Cardiology and Cardiovascular Medicine ,business ,Cohort study - Abstract
Aims We investigated long-term mortality associated with changes in left ventricular ejection fraction (LVEF) in a large, real-world patient cohort. Methods and results A total of 117 275 adults (63 ± 16 years, 46% women) had LVEF quantified by the same method ≥6 months apart. This included 17 343 cases (66 ± 15 years, 48% women) being initially investigated for heart failure (HF). During 3.3 [interquartile range (IQR) 1.7–6.0] years from first to last echocardiogram, median change in LVEF was −1 (IQR −8 to +5) units from a baseline of 62% (IQR 54–69%). During subsequent 7.6 (IQR 4.3–10.1) years of follow-up, 11 397 (9.7%) and 34 101 (29.1%) cases died from cardiovascular disease and all causes, respectively. Actual 5-year, all-cause mortality increased from 12% to 29% among those with the smallest to the largest decrease in LVEF (from 30 units); the adjusted risk of cardiovascular-related mortality increased two- to eightfold beyond a >10-unit decline in LVEF (vs. minimal change; P 30-unit increase to >30-unit decline in LVEF (vs. minimal change; P
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- 2021
10. The Australia and New Zealand Cardio‐Oncology Registry: evaluation of chemotherapy‐related cardiotoxicity in a national cohort of paediatric cancer patients
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Michelle Martin, Toby Trahair, Claudia Toro, Jonathon Forsey, Yonatan Diamond, John A. Heath, Louise E. Ludlow, Enzo Porello, David S. Celermajer, Jelena Saundankar, Lucy Holland, Michael Cheung, Peter Downie, Julian Ayer, Jennifer A. Byrne, Melissa Gabriel, Lorna McLeman, David A. Elliott, Glenn M. Marshall, Ben Costello, Marion K. Mateos, Emma Masango, Maurizio Marcocci, Thomas Walwyn, Andre La Gerche, Rachel Conyers, Rebecca Manudhane, Jeremy Lewin, Susan Donath, Rose Boutros, Roderick Walker, Daniel Lapirow, Ha N D Le, and Kylie D. Mason
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medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Population ,Antineoplastic Agents ,Disease ,030204 cardiovascular system & hematology ,Targeted therapy ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,Internal Medicine ,Humans ,Medicine ,Registries ,030212 general & internal medicine ,Young adult ,Child ,Intensive care medicine ,education ,Cardiotoxicity ,education.field_of_study ,business.industry ,Australia ,Cardiac reserve ,Cancer ,medicine.disease ,Pediatric cancer ,business ,New Zealand - Abstract
Cancer therapy related cardiac dysfunction (CTRCD) is an area of increasing focus, particularly during the survivorship period, for paediatric, adolescent and adult cancer survivors. With the advent of immunotherapy and targeted therapy, there is a new set of mechanisms from which paediatric and young adult patients with cancer may suffer cardiovascular injury. Furthermore, cardiovascular disease is the leading cause of morbidity and mortality in the survivorship period. The recently established Australian Cardio-Oncology Registry is the largest and only population-based cardiotoxicity database of paediatric and adolescent and young adult oncology patients in the world, and the first paediatric registry that will document cardiotoxicity caused by chemotherapy and novel targeted therapies using a prospective approach. The database is designed for comprehensive data collection and evaluation of the Australian practice in terms of diagnosis and management of CTRCD. Using the Australian Cardio-Oncology Registry critical clinical information will be collected regarding predisposing factors for the development of CTRCD, the rate of subclinical left ventricular dysfunction and transition to overt heart failure, further research into protectant molecules against cardiac dysfunction and aid in the discovery of which genetic variants predispose to CTRCD. A health economic arm of the study will assess the cost/benefit of both the registry and cardio-oncology clinical implementation. Finally, an imaging arm will establish if exercise cardiac magnetic resonance imaging and VO2 max testing is a more sensitive predictor of cardiac reserve in paediatric and adolescent and young adult oncology patients exposed to cardiac toxic therapies.
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- 2021
11. Ejection fraction and mortality: a nationwide register‐based cohort study of 499 153 women and men
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Jim Codde, David Playford, Simon Stewart, Neda Investigators, Geoff Strange, Philip Currie, Gregory M. Scalia, David S. Celermajer, and David L. Prior
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Male ,Cardiac function curve ,Register based ,medicine.medical_specialty ,030204 cardiovascular system & hematology ,Ventricular Function, Left ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Risk of mortality ,Humans ,Heart Failure ,Ejection fraction ,business.industry ,Hazard ratio ,Australia ,Stroke Volume ,Prognosis ,medicine.disease ,Confidence interval ,Heart failure ,Female ,Cardiology and Cardiovascular Medicine ,business ,Cohort study - Abstract
AIMS We investigated the sex-based risk of mortality across the spectrum of left ventricular ejection fraction (LVEF) in a large cohort of patients in Australia. METHODS AND RESULTS Quantified levels of LVEF from 237 046 women (48.1%) and 256 109 men undergoing first-time, routine echocardiography (2000-2019) were linked to 119 232 deaths (median 5.6 years of follow-up). Overall, 17.6% of men vs. 8.3% of women had an LVEF
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- 2020
12. Defibrillators in adult congenital heart disease: Long‐term risk of appropriate shocks, inappropriate shocks, and complications
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Mark A. McGuire, Benjamin M. Moore, Jacob Y. Cao, David S. Celermajer, and Rachael Cordina
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Adult ,Heart Defects, Congenital ,Male ,medicine.medical_specialty ,Adolescent ,Heart disease ,Population ,Disease ,030204 cardiovascular system & hematology ,Sudden cardiac death ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Secondary Prevention ,medicine ,Humans ,030212 general & internal medicine ,education ,Aged ,Tetralogy of Fallot ,education.field_of_study ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Defibrillators, Implantable ,Primary Prevention ,Death, Sudden, Cardiac ,Great arteries ,Shock (circulatory) ,Cardiology ,Female ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Complication - Abstract
Aims Sudden cardiac death (SCD) accounts for up to 25% of deaths in the adult congenital heart disease (ACHD) population. Current guidelines for defibrillator implantation are either extrapolated from acquired cardiac disease or are based upon single lesion studies, predominantly Tetralogy of Fallot (TOF). Defibrillator-related morbidity appears to be substantially higher in ACHD patients. Methods We retrospectively evaluated all patients in our ACHD database who received an implantable cardioverter-defibrillator (ICD) between 2000 and 2019, and who were ≥16 years old at time of implant. Patients were followed for appropriate shocks, inappropriate shocks, and complications. Results Of 4748 patients in our database, 59 patients (1.2%) underwent ICD implantation. ICDs were for primary prevention in 63% and secondary prevention in 37%. Over a median follow-up of 6.6 years, 24% received an appropriate shock, 27% an inappropriate shock, and 42% suffered a device-related complication (annualized risks of 3.2%, 3.6%, and 5.7%, respectively). There were no significant predictors of appropriate shocks or inappropriate shocks. All appropriate shocks in primary prevention patients occurred in TOF or transposition of the great arteries (TGA) with atrial switch, typically in the presence of multiple SCD risk factors. The majority of inappropriate shocks were due to supraventricular arrhythmias. Device-related mortality was 1.7% (0.3% per annum). Conclusions Appropriate shocks were relatively common in an ACHD ICD population followed in the long term. Device-related morbidity was significant. Although risk factors have been established for TOF, and to a lesser extent TGA, risk stratification for ICD implantation in ACHD remains challenging.
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- 2020
13. Diagnostic delay in pulmonary arterial hypertension: Insights from the Australian and New Zealand pulmonary hypertension registry
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Anne Keogh, Carolyn Corrigan, Eugene Kotlyar, James Anderson, Jeremy P. Wrobel, Trevor Williams, Nicholas Collins, Nathan Dwyer, Dominic Keating, Robert G. Weintraub, Helen Whitford, David S. Celermajer, P. Steele, Victor Khou, John Feenstra, Ken Whyte, Melanie Lavender, Tanya McWilliams, Mark Horrigan, Edmund M.T. Lau, and Geoff Strange
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Adult ,Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Delayed Diagnosis ,Kaplan-Meier Estimate ,Disease ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Epidemiology ,Humans ,Medicine ,Registries ,030212 general & internal medicine ,Survival analysis ,Pulmonary Arterial Hypertension ,business.industry ,Vascular disease ,Proportional hazards model ,Mortality rate ,Australia ,Hemodynamics ,Middle Aged ,medicine.disease ,Pulmonary hypertension ,Logistic Models ,030228 respiratory system ,Female ,business ,New Zealand ,Cohort study - Abstract
Background and objective Early diagnosis of PAH is clinically challenging. Patterns of diagnostic delay in Australian and New Zealand PAH populations have not been explored in large-scale studies. We aimed to evaluate the magnitude, risk factors and survival impact of diagnostic delay in Australian and New Zealand PAH patients. Methods A cohort study of PAH patients from the PHSANZ Registry diagnosed from 2004 to 2017 was performed. Diagnostic interval was the time from symptom onset to diagnostic right heart catheterization as recorded in the registry. Factors associated with diagnostic delay were analysed in a multivariate logistic regression model. Survival rates were compared across patients based on the time to diagnosis using Kaplan-Meier method and Cox regression. Results A total of 2044 patients were included in analysis. At diagnosis, median age was 58 years (IQR: 43-69), female-to-male ratio was 2.8:1 and majority of patients were in NYHA FC III-IV (82%). Median diagnostic interval was 1.2 years (IQR: 0.6-2.7). Age, CHD-PAH, obstructive sleep apnoea and peripheral vascular disease were independently associated with diagnostic interval of ≥1 year. No improvement in diagnostic interval was seen during the study period. Longer diagnostic interval was associated with decreased 5-year survival. Conclusion PAH patients experience significant diagnostic interval, which has not improved despite increased community awareness. Age, cardiovascular and respiratory comorbidities are significantly associated with longer time to diagnosis. Mortality rates appear higher in patients who experience longer diagnostic interval.
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- 2020
14. Characteristics of Bicuspid Aortic Valve Disease and Stenosis: The National Echo Database of Australia
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David S. Celermajer, Geoff Strange, David Playford, Michelle S. Lim, and Simon Stewart
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Adult ,Male ,medicine.medical_specialty ,Heart disease ,Regurgitation (circulation) ,Disease ,Constriction, Pathologic ,Cardiac Ultrasound ,cardiac ultrasound ,Bicuspid aortic valve ,Bicuspid Aortic Valve Disease ,Internal medicine ,medicine ,Humans ,Mitral Valve Stenosis ,Diseases of the circulatory (Cardiovascular) system ,Original Research ,business.industry ,Echo (computing) ,Congenital Heart Disease ,aortic stenosis ,regurgitation ,Aortic Valve Stenosis ,medicine.disease ,mortality ,Stenosis ,Echocardiography ,Valvular Heart Disease ,Aortic Valve ,RC666-701 ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background Bicuspid aortic valve (BAV) is the most common congenital heart disease in adults but is clinically heterogeneous. We aimed to describe the echocardiographic characteristics of BAV and compare patients with BAV with moderate‐to‐severe aortic stenosis (AS) with those with tricuspid aortic valve (TAV) stenosis. Methods and Results Using the National Echo Database of Australia, patients in whom BAV was identified were studied. Those with moderate‐to‐severe AS (mean gradient >20 mm Hg [BAV‐AS]) were compared with those with TAV and moderate‐to‐severe AS (TAV‐AS). Of 264 159 adults whose aortic valve morphology was specified, 4783 (1.8%) had confirmed BAV (aged 49.6±17.4 years, 69% men). Of these, 42% had no AS, and 46% had no aortic regurgitation. Moderate‐to‐severe AS was detected in a greater proportion of patients with BAV with a recorded mean gradient (n=1112, 34%) compared with those with TAV (n=4377, 4%; P P P P Conclusions In this large study of patients across the spectrum of BAV disease, the largest proportion had no significant valvulopathy or aortopathy. Compared with those with TAV‐AS, patients with BAV were more likely to have moderate‐to‐severe AS, have larger ascending aortas, and were over 2 decades younger at the time of AS diagnosis. Despite this, patients with BAV appear to have a more favorable prognosis when AS develops, compared with those with TAV‐AS. Registration URL: www.anzctr.org.au/ ; Unique identifier: ACTRN12617001387314.
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- 2021
15. Caring for adults with congenital heart disease in a regional setting
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Peter Watson Grant, D. Law, David S. Celermajer, Emily Mary O'Brien, and Jon H. Waites
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Adult ,Heart Defects, Congenital ,Male ,medicine.medical_specialty ,Adolescent ,Cardiac Care Facilities ,Heart disease ,030204 cardiovascular system & hematology ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Medicine ,030212 general & internal medicine ,Medical diagnosis ,Aged ,Aged, 80 and over ,Pregnancy ,Specialist referral ,business.industry ,Public Health, Environmental and Occupational Health ,Middle Aged ,medicine.disease ,Pulmonary hypertension ,Cardiac surgery ,Sonographer ,Emergency medicine ,Female ,Cardiology Service, Hospital ,Rural Health Services ,New South Wales ,Family Practice ,business ,Delivery of Health Care ,Needs Assessment - Abstract
Objective The number of adults with congenital heart disease has increased with improvements in surgical and medical management, posing a challenge for regional and rural settings, which might have difficulties accessing specialised professionals with congenital heart disease services. This study aims to ascertain the demographics and management of adults with congenital heart disease seen by a cardiology practice in regional Australia to better understand the needs of regional adults with congenital heart disease. Design A descriptive study using data from clinical notes collected between April 2013 and April 2016. Setting A private cardiology practice in Coffs Harbour, New South Wales. The practice has a treating cardiologist, senior sonographer, visiting cardiothoracic surgeon and visiting paediatric cardiologist. Participants One-hundred-and-one adults with congenital heart disease (age: 16-88 years; 55 women). Main outcome measures Congenital heart disease defect, lesion severity, referral reason, past surgery, pulmonary hypertension, cardiac surgery during the study, mortality, adherence with follow-up plans and specialist referral. Results Sixty-six patients had simple congenital heart disease, 24 had congenital heart disease of moderate complexity and 11 had congenital heart disease of great complexity. Most were referred for surveillance, seven were referred due to pregnancy and eight were new diagnoses. Six patients died, nine had cardiac operations and five were treated for pulmonary arterial hypertension. Overall adherence to the treating cardiologist's follow-up plans was 84%. All patients with congenital heart disease of great complexity were referred to congenital heart disease specialists. Conclusion A substantial number of patients had complex pathology, new diagnoses or required surgery, highlighting the importance of developing integrated services with the close support of outside specialists in managing adults with congenital heart disease in regional settings.
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- 2018
16. Heart failure admissions and poor subsequent outcomes in adults with congenital heart disease
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Rachael Cordina, Irina Kotchetkova, Sean Lal, Jacob Y. Cao, David S. Celermajer, and D. Jackson
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medicine.medical_specialty ,Framingham Risk Score ,Heart disease ,business.industry ,030204 cardiovascular system & hematology ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Heart failure ,Hospital admission ,medicine ,030212 general & internal medicine ,Cardiology and Cardiovascular Medicine ,Intensive care medicine ,business - Published
- 2017
17. Pathophysiology of exercise intolerance in pulmonary arterial hypertension
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Glen M. Davis, Derek Tran, Rachael Cordina, Edmund M.T. Lau, and David S. Celermajer
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,education.field_of_study ,business.industry ,Population ,Disease ,Exercise intolerance ,030204 cardiovascular system & hematology ,medicine.disease ,Pulmonary hypertension ,03 medical and health sciences ,0302 clinical medicine ,030228 respiratory system ,Afterload ,Internal medicine ,Heart failure ,medicine ,Cardiology ,Respiratory muscle ,medicine.symptom ,business ,education ,Maladaptation - Abstract
Pulmonary arterial hypertension (PAH) is a chronic disease with poor prognosis and important exercise limitation despite the proliferation of treatment options in the last decade. Chronically increased right ventricular (RV) afterload results in right heart failure and without treatment, rapid clinical deterioration is common. Exercise intolerance is the cardinal feature of the disease impacting upon quality of life and clinical outcome. The pathophysiological mechanisms that lead to reduced exercise capacity in this population are complex with ventriculoarterial uncoupling likely to be the predominant feature. The relative contributions of additional factors that contribute to exercise limitation beyond ventriculoarterial uncoupling have not been characterized. This review addresses these factors with a focus on recent developments and uncertainties. RV maladaptation and the intricate interplay between the heart, abnormal pulmonary vascular bed and peripheral factors such as dysfunction of the respiratory and peripheral muscles are discussed in detail.
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- 2017
18. Obesity, arterial function and arterial structure - a systematic review and meta-analysis
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Tim Gill, David S. Celermajer, Tommy Y. Cai, Crystal Man Ying Lee, Ian D. Caterson, Michael R. Skilton, and Jia Yi Anna Ne
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Arterial structure ,medicine.medical_specialty ,Nutrition and Dietetics ,Ovid medline ,business.industry ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Disease ,030204 cardiovascular system & hematology ,medicine.disease ,Obesity ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,Weight loss ,Internal medicine ,Meta-analysis ,medicine ,Cardiology ,Risk factor ,medicine.symptom ,business ,Arterial function - Abstract
SummaryObjective Obesity is an established risk factor for cardiovascular disease. The mechanisms by which obesity affects cardiovascular risk have not been fully elucidated. This paper reports a comprehensive systematic review and meta-analysis on obesity and two key aspects of vascular health using gold-standard non-invasive measures – arterial endothelial function (brachial flow-mediated dilatation) and subclinical atherosclerosis (carotid intima-media thickness). Methods Electronic searches for ‘Obesity and flow-mediated dilatation’ and ‘Obesity and intima-media thickness’ were performed using Ovid Medline and Embase databases. A meta-analysis was undertaken for brachial flow-mediated dilatation and carotid intima-media thickness to obtain pooled estimates for adults with obesity and those with healthy weight. Results Of the 5,810 articles retrieved, 19 studies on flow-mediated dilatation and 19 studies on intima-media thickness were included. Meta-analysis demonstrated that obesity was associated with lower flow-mediated dilatation (−1.92 % [95% CI −2.92, −0.92], P = 0.0002) and greater carotid intima-media thickness (0.07 mm [95% CI 0.05, 0.08], P
- Published
- 2017
19. Weight loss and carotid intima-media thickness-a meta-analysis
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David S. Celermajer, Ian D. Caterson, Si Qin Yeo, Jia Yi Anna Ne, Michael R. Skilton, and Crystal Man Ying Lee
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medicine.medical_specialty ,Nutrition and Dietetics ,business.industry ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) ,Disease ,030204 cardiovascular system & hematology ,medicine.disease ,Obesity ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Pooled variance ,Intima-media thickness ,Weight loss ,Internal medicine ,Subclinical atherosclerosis ,Meta-analysis ,medicine ,Cardiology ,030212 general & internal medicine ,medicine.symptom ,Risk factor ,business - Abstract
Objective Obesity is a risk factor for clinical cardiovascular disease, putatively via increased burden of atherosclerosis. It remains contentious as to whether weight loss in people with obesity is accompanied by a reduction in intima-media thickness, a noninvasive marker of subclinical atherosclerosis, consistent with a lowering of risk of cardiovascular events. Methods A systematic literature search was performed to identify all surgical and nonsurgical weight loss interventions that reported intima-media thickness. A meta-analysis was undertaken to obtain pooled estimates for change in intima-media thickness. Results From the 3,197 articles screened, 9 studies were included in the meta-analysis, with a total of 393 participants who lost an average of 16 kg (95% CI 9.4–22.5) of body weight over an average follow-up of 20 months. The pooled mean change in carotid intima-media thickness was −0.03 mm (95% CI −0.05 to −0.01), which was similar between surgical and nonsurgical interventions. Conclusions In people with obesity, weight loss was associated with a reduction in carotid intima-media thickness, consistent with a lowering in risk of cardiovascular events.
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- 2016
20. Quantifying right atrial filling and emptying: A 4D-flow MRI study
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Gemma A. Figtree, David S. Celermajer, Stuart M. Grieve, Clare Arnott, Fraser M. Callaghan, and Shelby Kutty
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Physics ,medicine.diagnostic_test ,Beat (acoustics) ,Magnetic resonance imaging ,Blood flow ,030204 cardiovascular system & hematology ,Kinetic energy ,030218 nuclear medicine & medical imaging ,Vortex ,03 medical and health sciences ,0302 clinical medicine ,Nuclear magnetic resonance ,medicine ,Fluid dynamics ,Radiology, Nuclear Medicine and imaging ,Streamlines, streaklines, and pathlines ,Systole - Abstract
Purpose To quantitatively characterize the central role of vortex formation on the flow patterns and energy transfer within the right atrium (RA). Materials and Methods 4D-flow magnetic resonance imaging (MRI) data with multiple encoding velocities was acquired in 12 healthy subjects at 3T. Particles entering the RA were classified according to the origin of entry. Vortex membership was numerically derived by assessing the location of pathline center of curvature relative to the vortex core, defined by Q-criteria. Flow dynamics and energetics were assessed using paired t-tests. Results The majority of flow (74%) passes through the RA in a single beat, with a very small volume fraction retained longer than two beats (
- Published
- 2016
21. A binational registry of adults with pulmonary arterial hypertension complicating congenital heart disease
- Author
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Nathan Dwyer, Hayley S. Whitford, Chris Frampton, Patrick Disney, David S. Celermajer, M. Rose, Anne Keogh, Robert G. Weintraub, Leeanne Grigg, Fiona Kermeen, Eugene Kotlyar, David Tanous, G. Strange, Clare O'Donnell, and Andrew Bullock
- Subjects
Pediatrics ,medicine.medical_specialty ,education.field_of_study ,Heart disease ,business.industry ,Population ,Retrospective cohort study ,medicine.disease ,New york heart association ,Quality of life ,Eisenmenger syndrome ,Internal Medicine ,medicine ,Intensive care medicine ,Complication ,business ,education ,Developed country - Abstract
Background The management of children with congenital heart disease (CHD) has improved over recent decades and several patients surviving with CHD into adulthood are increasing. In developed countries, there are now as many adults as there are children living with CHD. Pulmonary arterial hypertension (PAH) occurs in ∼ 5% of patients with CHD. Aim We aimed to understand the characteristics and outcomes of this emerging population. Methods We collected data retrospectively and prospectively from 12 contributing centres across Australia and New Zealand (2010-2013). Patients were included if they had been diagnosed with PAH and CHD and had been seen once in an adult centre after 1 January 2000. Results Of 360 patients with CHD-PAH, 60% were female and 90% were New York Heart Association functional class II or III at the time of adult diagnosis of PAH. Mean age at diagnosis of PAH in adulthood was 31.2 ± 14 years, and on average, patients were diagnosed with PAH 6 years after symptom onset. All-cause mortality was 12% at 5 years, 21% at 10 years and 31% at 15 years. One hundred and six patients (30%) experienced 247 hospitalisations during 2936 patient years of follow up. Eighty-nine per cent of patients were prescribed PAH specific therapy (mean exposure of 4.0 years). Conclusions Adults with PAH and CHD often have this diagnosis made after significant delay, and have substantial medium-term morbidity and mortality. This suggests a need for children transitioning to adult care with CHD to be closely monitored for this complication.
- Published
- 2015
22. Use of multi-velocity encoding 4D flow MRI to improve quantification of flow patterns in the aorta
- Author
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David S. Celermajer, Michael P. Vallely, Stuart M. Grieve, Fraser M. Callaghan, Gemma A. Figtree, Rebecca Kozor, and Andrew G. Sherrah
- Subjects
medicine.diagnostic_test ,Magnetic resonance imaging ,030204 cardiovascular system & hematology ,computer.software_genre ,Curvature ,Flow measurement ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Flow (mathematics) ,Voxel ,medicine ,Radiology, Nuclear Medicine and imaging ,Vector field ,Streamlines, streaklines, and pathlines ,computer ,Biomedical engineering ,Mathematics ,Euclidean vector - Abstract
Purpose To show that the use of a multi-velocity encoding (VENC) 4D-flow approach offers significant improvements in the characterization of complex flow in the aorta. Four-dimensional flow magnetic resonance imaging (MRI) (4D-flow) can be used to measure complex flow patterns and dynamics in the heart and major vessels. The quality of the information derived from these measures is dependent on the accuracy of the vector field, which is limited by the vector-to-noise ratio. Materials and Methods A 4D-flow protocol involving three different VENC values of 150, 60, and 20 cm/s was performed on six control subjects and nine patients with type-B chronic aortic dissection at 3T MRI. Data were processed using a single VENC value (150 cm/s) or using a fused dataset that selected the lowest appropriate VENC for each voxel. Performance was analyzed by measuring spatial vector angular correlation, magnitude correlation, temporal vector conservation, and “real-world” streamline tracing performance. Results The multi-VENC approach provided a 31% improvement in spatial and 53% improvement in temporal precision of velocity vector measurements during the mid-late diastolic period, where 99% of the flow vectors in the normal aorta are below 20 cm/s. In low-flow conditions this resulted in practical improvements of greater than 50% in pathline tracking and streamline tracing quantified by streamline curvature measurements. Conclusion A multi-VENC 4D-flow approach provides accurate vector data across normal physiological velocities observed in the aorta, dramatically improving outputs such as pathline tracking, streamline estimation, and further advanced analyses.J. Magn. Reson. Imaging 2015.
- Published
- 2015
23. Psychological distress and self-rated oral health among a convenience sample of Indigenous Australians
- Author
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Louise J. Maple-Brown, Gary D. Slade, Michael R. Skilton, Najith Amarasena, David S. Celermajer, Lisa Jamieson, Alex Brown, Kerin O'Dea, Kostas Kapellas, and Mark Bartold
- Subjects
medicine.medical_specialty ,business.industry ,Confounding ,Public Health, Environmental and Occupational Health ,Psychological distress ,Convenience sample ,Odds ratio ,Oral health ,Logistic regression ,Indigenous ,Toothache ,medicine ,medicine.symptom ,business ,Psychiatry ,General Dentistry ,Demography - Abstract
Objectives This study sought to: a) estimate the frequency of poor self-rated oral health as assessed by a summary measure; b) compare frequency according to sociodemographic, behavioral, and psychological distress factors; and (3) determine if psychological distress was associated with poor self-rated oral health after adjusting for confounding. Methods Data were from a convenience sample of Indigenous Australian adults (n = 289) residing in Australia's Northern Territory. Poor self-rated oral health was defined as reported experience of toothache, poor dental appearance or food avoidance in the last 12 months. A logistic regression model was used to evaluate socio-demographic, behavioral, and psychological distress associations with poor self-rated oral health (SROH). Effects were quantified as odds ratios (OR). Results The frequency of poor SROH was 73.7 percent. High psychological distress, measured by a Kessler-6 score ≥8, was experienced by 33.9 percent of participants. Poor SROH was associated with high levels of psychological distress, being older, being female, and usually visiting a dentist because of a problem. In the multivariable model, factors that were significantly associated with poor SROH after adjustment for other covariates included having a high level of psychological distress (OR 2.74, 95% CI 1.25–6.00), being female (OR 2.22, 95% CI 1.03–4.78), and usually visiting a dentist because of a problem (OR 3.57, 95% CI 1.89–6.76). Conclusions Poor self-rated oral health and high levels of psychological distress were both highly frequent among this vulnerable population. Psychological distress was significantly associated with poor self-rated oral health after adjustment for confounding.
- Published
- 2014
24. Ophthalmological consequences of cyanotic congenital heart disease: vascular parameters and nerve fibre layer
- Author
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Mojtaba Golzan, John Leaney, Rachael Cordina, Stuart L. Graham, David S. Celermajer, and Stuart M. Grieve
- Subjects
Intraocular pressure ,medicine.medical_specialty ,Retina ,Visual acuity ,genetic structures ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,Retinal ,eye diseases ,Scanning laser ophthalmoscopy ,Surgery ,Bilateral Cataracts ,Visual field ,Ophthalmology ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,medicine ,medicine.symptom ,business - Abstract
Background This study investigated the long-term ophthalmological consequences of cyanotic congenital heart disease (CHD). Design Cross-sectional study, tertiary referral setting. Participants Thirteen adults with cyanotic CHD (40 ± 4 years). Age- and sex-matched healthy controls underwent aspects of the protocol. Methods Cyanosed subjects had a full ophthalmic examination, visual fields, scanning laser ophthalmoscopy and optical coherence tomography to assess retinal nerve fibre layer (RNFL), retinal photography and cerebral magnetic resonance imaging (MRI). Main Outcome Measures RNFL thickness and quantitative analysis of retinal vessels with fractal dimension, branching and central retinal arterial equivalent (CRAE) and central retinal venous equivalent (CRVE). Results No abnormalities of anatomy, motility, intraocular pressure or anterior segments were detected apart from one subject who had bilateral cataracts. Corrected visual acuity was normal in all but one cyanosed subject. Clinical examination revealed dilated retinal vasculature in 12/13 cyanosed subjects and increased tortuosity in 8/13. In the setting of cyanosis, skeletonized retinal arterial and venous beds had higher fractal dimension and increased branching (P ≤ 0.01, n = 11 for all); retinal vessels were dilated (CRAE: 227 vs. 183, n = 11, P
- Published
- 2014
25. Introduction of an interdisciplinary heart team-based transcatheter aortic valve implantation programme: short and mid-term outcomes
- Author
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Gonzalo J. Martinez, S. K. Jaijee, Michael Seco, Michael P. Vallely, Martin K.C. Ng, Michael K. Wilson, David S. Celermajer, Bruce Cartwright, Mark Raymond Adams, and Paul Forrest
- Subjects
education.field_of_study ,medicine.medical_specialty ,Transcatheter aortic ,business.industry ,Population ,Hemodynamics ,Regurgitation (circulation) ,medicine.disease ,Surgery ,Aortic valve replacement ,Heart failure ,Aortic valve stenosis ,Heart team ,Internal Medicine ,Medicine ,business ,education - Abstract
Background Transcatheter aortic valve implantation (TAVI) has been developed to treat symptomatic aortic stenosis in patients deemed too high risk for open-heart surgery. To address this complex population, an interdisciplinary heart team approach was proposed. Aim Present the short- and mid-term outcomes of the first 100 patients in the Royal Prince Alfred Hospital multidisciplinary TAVI programme. Methods Single-centre registry. Baseline and procedural data were prospectively recorded. Outcomes were recorded according to Valve Academic Research Consortium – version 2 guidelines. Results All patients underwent a comprehensive interdisciplinary pre-procedural evaluation. Sixty-eight transfemoral and 32 transapical implantations were performed. Mean age was 82 (±8.9) years old with an average logistic EuroSCORE of 33. Although 13 procedures had major complications, there was no intraprocedural mortality. During the first month, 9% of patients were re-admitted due to heart failure and 13% had a permanent pacemaker implanted. A 3% 30-day and 8% follow-up (mean 17 months) mortalities were recorded. While no significant differences in the rate of complications were found between the first and second half of the experience, all cases of mortality within 30 days (n = 3) occurred in the initial half. Sustained haemodynamic results were obtained with TAVI (immediate mean aortic valve gradient reduction from 47 to 9 mmHg; 1-year echocardiographic gradient 9.9 mmHg, with no moderate or severe aortic regurgitation). Conclusion Excellent results can be achieved with TAVI in very high-risk patients at an Australian institution. A comprehensive evaluation based on a heart team can overcome most of the difficulties imposed by this challenging population.
- Published
- 2014
26. Imatinib for the Treatment of Pulmonary Arterial Hypertension and Pulmonary Capillary Hemangiomatosis
- Author
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David S. Celermajer, Ravin Hettiarachchi, G. Kumarasinghe, Kavitha Muthiah, Dhruv Nayyar, Anne Keogh, and Eugene Kotlyar
- Subjects
Pulmonary and Respiratory Medicine ,biology ,business.industry ,Growth factor ,medicine.medical_treatment ,Antagonist ,Case Report ,Imatinib ,Pulmonary capillary hemangiomatosis ,Pharmacology ,medicine.disease ,Pulmonary hypertension ,Pathogenesis ,medicine ,biology.protein ,Receptor ,business ,neoplasms ,Platelet-derived growth factor receptor ,medicine.drug - Abstract
Despite currently available treatments, the prognoses of pulmonary arterial hypertension (PAH) and pulmonary capillary hemangiomatosis (PCH) remain poor. Platelet-derived growth factor and its receptor (PDGFR) have been implicated in the pathogenesis of pulmonary hypertension in PAH and PCH. Imatinib, a PDGFR antagonist, may be beneficial in the treatment of both conditions because of its potent antiproliferative effect. We report two cases that demonstrate the potential for safe and efficacious use of imatinib in PAH and PCH.
- Published
- 2014
27. The Australia and New Zealand Fontan Registry: description and initial results from the first population-based Fontan registry
- Author
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David S. Celermajer, Robert G. Weintraub, John C. Galati, Thomas L. Gentles, Ajay J. Iyengar, Gavin R. Wheaton, Andrew Bullock, Yves d'Udekem, Robert N. Justo, and David S. Winlaw
- Subjects
Research design ,medicine.medical_specialty ,education.field_of_study ,Pediatrics ,Heart disease ,business.industry ,medicine.medical_treatment ,Population ,Population based ,medicine.disease ,Hypoplastic left heart syndrome ,Fontan procedure ,Epidemiology ,Internal Medicine ,medicine ,Lost to follow-up ,education ,business - Abstract
Background: The Fontan procedure is the final in a series of staged palliations for single-ventricle congenital heart disease, which encompasses rare and heterogeneous cardiac lesions. It represents an unusual and novel physiological state characterised by absence of a subpulmonary ventricle. Aims: The population is growing steadily, prompting creation of this registry to study their epidemiology, demographic trends, treatment and outcomes. Methods: This multicentre, binational, prospective and retrospective, web-based registry involving all congenital cardiac centres in the region has identified nearly all Fontan patients in Australia and New Zealand. Patients identified retrospectively were approached for recruitment. New recipients are automatically enrolled prospectively unless they choose to opt-out. Follow-up data are collected yearly. Results: Baseline data were obtained in 1072 patients as at 1 January 2011. Ninety-nine patients died; 64 were lost to follow up. Forty-four per cent of patients lost were between 20 and 30 years of age. The size of the Fontan population is increasing steadily. Among 973 living patients, 541 (56%) gave consent for prospective collection of follow up. Between 1 January 2011 and 1 January 2013, an additional 47 subjects were enrolled prospectively. The current proportion of patients operated with hypoplastic left heart syndrome is currently 29% and is growing rapidly. Conclusion: The population surviving after the Fontan procedure has been growing in recent decades, especially since survival with hypoplastic left heart syndrome has improved. The Australia and New Zealand Fontan Registry provides population-based data, and only large databases like this will give opportunities for understanding the population and performing prospective trials.
- Published
- 2014
28. Screening and treating pulmonary arterial hypertension in a tertiary hospital-based multidisciplinary clinic: the first 200 patients
- Author
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M. K. Manghani, David S. Celermajer, Roger Garsia, Peter Youssef, Paul J. Torzillo, Iven H. Young, D. Fowler, and A. J. Low
- Subjects
medicine.medical_specialty ,Pediatrics ,Heart disease ,Sildenafil ,business.industry ,Tertiary referral hospital ,medicine.disease ,Pulmonary hypertension ,Bosentan ,Pulmonary function testing ,chemistry.chemical_compound ,chemistry ,Interquartile range ,medicine.artery ,Pulmonary artery ,Internal Medicine ,medicine ,Intensive care medicine ,business ,medicine.drug - Abstract
Background Pulmonary arterial hypertension (PAH) is an increasingly recognised serious illness with insidious onset, delayed diagnosis, complex diagnostic algorithms and poor prognosis, but with recently available effective treatments. Aims To efficiently diagnose and to offer treatment for PAH, we established a multidisciplinary service in 2005, where patients attend a clinic staffed by specialists in cardiology, respiratory medicine, rheumatology and immunology in a tertiary referral hospital setting. Methods We studied the first 200 patients referred. Serology, echocardiography, lung function tests, high-resolution computed tomography, World Health Organisation Class determination and 6-min walk tests and/or right heart catheterisation were performed, as clinically indicated. Results Of the 200 patients seen, 66 had confirmed pulmonary hypertension (mean pulmonary artery pressure > 25 mmHg) diagnosed on echocardiography ± right heart catheterisation. Of these patients, 58 had catheter-proven PAH (mean pulmonary artery pressure > 25 mmHg with mean wedge pressure < 15 mmHg). Underlying diagnoses for the confirmed PAH patients were idiopathic (32), scleroderma-associated (14), other connective tissue disease (4) and associated with congenital heart disease (8). Patients with confirmed PAH were commenced on PAH-specific therapy – initially bosentan in the majority but sildenafil, and iloprost were occasionally used initially for patient-specific reasons. Median time from when the patient first called the clinic to prescription of therapy was 16 days (interquartile range; 0–31 days). All surviving patients with PAH have attended for regular 6-monthly follow-up visits with a 100% retention rate up to 4 years. Conclusion A multidisciplinary clinic can provide efficient diagnosis and rapid triage to PAH-specific therapy, if appropriate. Retention rates remain high, at follow up.
- Published
- 2013
29. Ironic case of hepatic dysfunction following the global withdrawal of sitaxentan
- Author
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David S. Celermajer, G.W. Don, F. Joseph, and Tamera J. Corte
- Subjects
Endothelin Receptor Antagonists ,medicine.medical_specialty ,Hypertension, Pulmonary ,Thiophenes ,Piperazines ,Sildenafil Citrate ,Safety-Based Drug Withdrawals ,Liver Function Tests ,Sitaxentan ,Internal Medicine ,medicine ,Humans ,Sulfones ,Intensive care medicine ,Antihypertensive Agents ,Sulfonamides ,Scleroderma, Systemic ,business.industry ,Bosentan ,Isoxazoles ,Middle Aged ,Phosphodiesterase 5 Inhibitors ,Liver ,Purines ,Anesthesia ,Female ,business ,Hepatic dysfunction ,medicine.drug - Abstract
A patient with pulmonary arterial hypertension secondary to systemic sclerosis was successfully treated with sitaxentan prior to its worldwide withdrawal (because of hepatotoxicity concerns), but then ironically experienced acute hepatic dysfunction during substitute bosentan therapy, and was eventually stabilised on a phosphodiesterase-5 inhibitor.
- Published
- 2012
30. Congenital heart disease-associated pulmonary arterial hypertension: preliminary results from a novel registry
- Author
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David S. Celermajer, Leeanne Grigg, M. Rose, R. Weintraub, Clare O O'Donnell, Geoff Strange, Ingrid King, Suzanna Vidmar, Sarah Arnup, and Fiona Kermeen
- Subjects
Pediatrics ,medicine.medical_specialty ,Down syndrome ,Heart disease ,business.industry ,medicine.disease ,Pulmonary hypertension ,World health ,Eisenmenger syndrome ,Internal Medicine ,medicine ,Young adult ,Prospective cohort study ,business ,Associated Pulmonary Arterial Hypertension - Abstract
Background/Aims: Pulmonary arterial hypertension (PAH) frequently accompanies childhood congenital heart disease (CHD) and may persist into adult life. The advent of specific PAH therapies for PAH prompted formation of a national Australian and New Zealand registry in 2010 to document the incidence, demographics, presentation and outcomes for these patients. Methods: This multicentre, prospective, web-based registry enrols patients with CHD-associated PAH being followed in a tertiary centre. The inclusion criteria stipulated patient age ≥16 years, a measured mean pulmonary arterial pressure >25 mmHg at rest or echocardiographical evidence of PAH or a diagnosis of Eisenmenger syndrome, and followed since 1 January 2000. A single observer collected standardised data during a series of site visits. Results: Of the first 50 patients enrolled, 30 (60%) were female. The mean age (standard deviation (SD)) at the time of PAH diagnosis or confirmation in an adult centre was 27.23 (10.07) years, and 32 (64%) patients are currently aged >30 years. Fourteen (28%) patients were in World Health Organization Functional Class II and 36 (72%) in Class III at the time of diagnosis. Forty-seven of 50 (94%) had congenital systemic-pulmonary shunts, and 36 (72%) never underwent intervention. Thirteen (26%) had Down syndrome. Confirmation of PAH by recent cardiac catheterisation was available in 30 (60%) subjects. During follow up, a total of 32 (64%) patients received a PAH-specific therapy. Conclusions: CHD associated with PAH in adult life has resulted in a new population with unique needs. This registry will allow documentation of clinical course and long-term outcomes for these patients.
- Published
- 2012
31. Developmental Origins of Health and Disease: Who knows? Who cares?
- Author
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Adrienne Gordon, Hala Phipps, Ian D. Caterson, Charlotte Hespe, Claire L. O’Reilly, David S. Celermajer, Jon Hyett, Nicholas R. Fuller, Michael R. Skilton, and Rowena L McMullan
- Subjects
medicine.medical_specialty ,030219 obstetrics & reproductive medicine ,business.industry ,MEDLINE ,Disease ,Child development ,03 medical and health sciences ,0302 clinical medicine ,Pediatrics, Perinatology and Child Health ,Medicine ,030212 general & internal medicine ,business ,Psychiatry ,Preventive healthcare - Published
- 2017
32. Snoring is not associated with adverse effects on blood pressure, arterial structure or function in 8-year-old children: The Childhood Asthma Prevention Study (CAPS)
- Author
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Ronald R. Grunstein, David S. Celermajer, Nathaniel S. Marshall, Julian Ayer, Craig L. Phillips, Guy B. Marks, Jason A. Harmer, and Brett G. Toelle
- Subjects
medicine.medical_specialty ,education.field_of_study ,biology ,business.industry ,C-reactive protein ,Population ,medicine.disease ,Confidence interval ,respiratory tract diseases ,Blood pressure ,Intima-media thickness ,Internal medicine ,Pediatrics, Perinatology and Child Health ,biology.protein ,Cardiology ,Arterial stiffness ,Medicine ,business ,education ,Body mass index ,Pulse wave velocity - Abstract
Aims: To study the association between childhood snoring and cardiovascular risk factors. Methods: Cross-sectional analyses of a population-based birth cohort, who had been participants in a randomised controlled trial of interventions to prevent asthma and who were assessed at age 8 years. The presence and frequency of snoring were assessed by parent-completed questionnaire. We measured a wide range of cardiovascular function markers including non-fasting serum lipoproteins, blood pressure, high-sensitivity C-reactive protein, carotid artery intima media thickness (by ultrasound), brachial pulse wave velocity and augmentation index (by applanation tonometry). Results: Of 409 children whose snoring status was assessed at age 8 years, 321 had lipid and 386 had arterial structure and function measurements. Snoring was not independently associated with blood pressure, carotid artery intima media thickness or measures of arterial stiffness (all P > 0.05). Increasing snoring frequency was independently associated with lower high-density lipoprotein cholesterol (−0.032 g/dL per step, 95% confidence interval −0.060 to −0.003), although the difference in high-density lipoprotein between snorers and non-snorers was not significant (P = 0.052). An association of snoring frequency with brachial pulse wave velocity differed according to body mass index (P = 0.03) and was the reverse of that expected. Conclusions: Parentally reported snoring was not independently associated with adverse measurements of metabolic markers, vascular structure or function in 8-year-old children. Parental reports of snoring may be below the treatment threshold without additional diagnosis via sleep studies.
- Published
- 2011
33. Increased tissue factor activity in monocytes from obese young adults
- Author
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Katherine Steinbeck, David S. Celermajer, S. Ben Freedman, Julian Ayer, and Changjie Song
- Subjects
Pharmacology ,medicine.medical_specialty ,biology ,Physiology ,business.industry ,Leptin ,Insulin ,medicine.medical_treatment ,C-reactive protein ,Peripheral blood mononuclear cell ,Tissue factor ,Endocrinology ,Physiology (medical) ,Internal medicine ,medicine ,biology.protein ,Resistin ,Serum amyloid A ,business ,Serum Amyloid A Protein - Abstract
Summary 1. The relationship between inflammation, obesity-related proteins and tissue factor (TF), the major initiator of the extrinsic clotting cascade, is not well understood. We examined if basal and stimulated peripheral blood mononuclear cell (PBMC) TF-procoagulant activity (PCA) was higher in obese subjects and examined the effects of leptin, resistin and serum amyloid A (SAA). 2. PBMC from 12 obese (six male, aged 29 ± 4 years, body mass index 46.0 ± 8.7 kg/m2) and 12 age- and sex-matched lean controls were cultured either unstimulated or stimulated by lipopolysaccharide (LPS; 10 ρg/mL and 100 ng/mL, for 4–16 h) or SAA (1 ng/mL, 25 ng/mL, 250 ng/mL, for 4 h). Separately, PBMC from lean subjects were cultured unstimulated with leptin (100 ρg/mL, 1 ng/mL, 10 ng/mL, 100 ng/mL, 1 μg/mL), resistin (0.1 ng/mL, 1 ng/mL, 10 ng/mL, 100 ng/mL) or leptin (100 ng/mL) plus LPS (100 ρg/mL). TF-PCA was determined by a 1-stage plasma recalcification assay. 3. Four-hour unstimulated PBMC TF-PCA was greater in the obese (90.4 ± 16.5 vs 39.9 ± 4.7 mu TF/106 PBMC, P = 0.01). After 4 h stimulation with SAA or LPS the TF-PCA was similar. Unstimulated TF-PCA correlated with log serum high sensitivity C- reactive protein (hs-CRP) (r = 0.42, P = 0.04) and insulin (r = 0.44, P = 0.048), but not with log serum SAA (r = 0.192, P = 0.55). Physiological concentrations of leptin or resistin and leptin plus LPS did not increase TF-PCA in PBMC from lean subjects. 4. Basal PBMC TF-PCA is higher in the obese and is associated with serum hs-CRP. The obesity-related proteins SAA, leptin and resistin are unlikely to play a major role in increasing PBMC TF-PCA.
- Published
- 2010
34. Risk factors for cardiovascular disease do not fully explain differences in carotid intima-media thickness between Indigenous and European Australians without diabetes
- Author
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David S. Celermajer, Louise J. Maple-Brown, Kerin O'Dea, Allison M. Hodge, Joan Cunningham, Maple-Brown, L, Hodge, A, Cunningham, J, Celemajer, DS, and O'Dea, K
- Subjects
Adult ,Blood Glucose ,Male ,Tunica media ,European Australians ,medicine.medical_specialty ,Indigenous Australians ,carotid intima-media thickness ,Endocrinology, Diabetes and Metabolism ,Blood lipids ,Indigenous ,Endocrinology ,Risk Factors ,cardiovascular disease ,Internal medicine ,Diabetes mellitus ,Epidemiology ,Diabetes Mellitus ,medicine ,Humans ,Risk factor ,Ultrasonography ,diabetes ,business.industry ,differences ,Australia ,Middle Aged ,Anthropometry ,medicine.disease ,Lipids ,Surgery ,C-Reactive Protein ,Carotid Arteries ,medicine.anatomical_structure ,risk factor ,Intima-media thickness ,Cardiovascular Diseases ,Female ,Tunica Intima ,Tunica Media ,business ,Demography - Abstract
Summary Objective To investigate whether cardiovascular risk factors can explain the higher carotid intima–media thickness (CIMT) in Indigenous compared with European Australians. Design Cross-sectional study in three subgroups. Patients Non-diabetic urban European (n = 86), urban Indigenous (n = 69), and remote Indigenous (n = 60) Australians aged 25–64 years. Measurements CIMT, age, sex, anthropometry, blood pressure, smoking status, fasting glucose and insulin, haemoglobin (Hb)A1c, homocysteine, C-reactive protein (CRP), lipids, urinary albumin and creatinine. Results CIMT and levels of risk factors, except fasting glucose and total cholesterol, worsened across the three groups. Logn fasting insulin [β = 0·022, 95% confidence interval (CI) 0–0·0439], age (β = 0·006, 95% CI 0·004–0·007), gender (female β = –0·005 vs. male, 95% CI –0·084 to –0·026), mean arterial pressure (MAP) (β = 0·001, 95% CI 0·001–0·002) and ethnicity/location [urban Indigenous (β = 0·027, 95% CI –0·010 to 0·064 vs. European); remote Indigenous (β = 0·083, 95% CI 0·042–0·123 vs. European)] explained 41% of variance in CIMT. Significant interactions were seen for ethnicity/location with age (P = 0·014) and MAP (P = 0·018). Age was consistently associated with CIMT across the three populations, and was associated with larger increments in CIMT for the Indigenous subgroups (β = 0·007, 95% CI 0·005–0·009 urban; β = 0·007, 95% CI 0·004–0·010 remote) compared with Europeans (β = 0·003, 95% CI 0·002–0·006) in models including age, sex and MAP. MAP was only associated with CIMT in the remote Indigenous subgroup. Conclusion After adjusting for selected risk factors, CIMT in remote Indigenous participants was still higher than in Europeans. The slope of the association between age and CIMT steepened from urban Europeans to remote Indigenous.
- Published
- 2009
35. MEASUREMENT OF PULMONARY FLOW RESERVE IN HIGHER PRIMATES
- Author
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Richard Waugh, Kim H. Chan, C. Chawantanpipat, Rahn Ilsar, Annemarie Hennessy, David S. Celermajer, and Martin K.C. Ng
- Subjects
Male ,Pulmonary Circulation ,Adenosine ,Physiology ,Vasodilator Agents ,Hemodynamics ,Hyperemia ,Vasodilation ,Microcirculation ,Hyperaemia ,Heart Rate ,Papaverine ,Physiology (medical) ,medicine ,Animals ,Pharmacology ,Lung ,business.industry ,Ultrasonography, Doppler ,medicine.anatomical_structure ,Anesthesia ,Microvessels ,Female ,Vascular Resistance ,medicine.symptom ,business ,Blood Flow Velocity ,Papio ,Artery ,medicine.drug - Abstract
1. There are currently limited diagnostic methods for assessing the integrity of the pulmonary microvasculature. We hypothesized that a novel, invasively determined physiological index of 'pulmonary flow reserve' (PFR = maximal hyperaemic pulmonary blood flow divided by basal pulmonary flow) may facilitate microvascular assessment in the lung. Therefore, we developed a baboon model in which to: (i) validate the use of Doppler flow velocity for PFR assessment; (ii) define the optimal drug and dose regimen for attainment of maximal pulmonary hyperaemia; and (iii) demonstrate the feasibility of measuring PFR in healthy higher primates. 2. Doppler sensor guidewires were placed in segmental pulmonary arteries of 11 ketamine-anaesthetized baboons. Vessel diameter, flow velocity and haemodynamics were recorded before and after direct intrapulmonary artery administration of saline, adenosine (50-500 microg/kg per min) and papaverine (3-60 mg), enabling calculation of PFR. 3. Saline (either bolus injection or infusion) did not alter vessel diameter or flow velocity (P0.1), validating local drug administration. Both adenosine and papaverine induced dose-dependent increases in flow velocity from baseline (from 22.5 +/- 2.3 to 32.7 +/- 4.8 cm/s for 400-500 microg/kg per min adenosine; and from 23.9 +/- 1.1 to 34.6 +/- 4.0 cm/s for 24 mg papaverine; both P0.0001), without affecting pulmonary artery pressure or vessel diameter (P0.3). Healthy primate PFR values were 1.35 +/- 0.10 and 1.39 +/- 0.10 using 200 microg/kg per min adenosine and 24 mg papaverine, respectively (P0.8). 4. In conclusion, pulmonary flow reserve in higher primates can be assessed using Doppler sensor guidewire and either adenosine or papaverine as microvascular hyperaemic agents. Measurements of PFR may facilitate pulmonary microvascular assessments.
- Published
- 2009
36. The effects of obesity and non-pharmacological weight loss on vascular and ventricular function and structure
- Author
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Jason A. Harmer, Michael R. Skilton, David S. Celermajer, Janet Franklin, Ian D. Caterson, David R. Sullivan, Georgina Loughnan, Shirley Nakhla, and Daniel P Sieveking
- Subjects
Adult ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Diastole ,Vascular Cell Adhesion Molecule-1 ,Inflammation ,Fibrinogen ,Ventricular Dysfunction, Left ,chemistry.chemical_compound ,Endocrinology ,Weight loss ,Internal medicine ,Weight Loss ,Internal Medicine ,medicine ,Humans ,Obesity ,Prospective Studies ,Prospective cohort study ,Exercise ,Chi-Square Distribution ,business.industry ,Cholesterol ,Case-control study ,Intercellular Adhesion Molecule-1 ,medicine.disease ,Carotid Arteries ,chemistry ,Echocardiography ,Regional Blood Flow ,Case-Control Studies ,Female ,medicine.symptom ,E-Selectin ,Tunica Intima ,business ,Biomarkers ,medicine.drug - Abstract
Aims: The mechanisms by which obesity confers increased cardiovascular risk and the effects of moderate weight loss on cardiovascular health are incompletely understood. We sought to characterize the preclinical changes in cardiac and vascular health that accompany obesity and the influence of lifestyle modification on these parameters. Methods: Preclinical markers of vasculopathy in resistance vessels and conduit arteries and left ventricular structure and function were assessed in 39 obese subjects (BMI > 30 kg/m2) and 11 healthy weight controls. The influence of serum on cellular adhesion molecule (CAM) expression on human endothelial cells was studied ex vivo in a subgroup of 13 obese and nine healthy weight subjects. These analyses were repeated in all 17 of the obese subjects who complied with 4–9 months of lifestyle modification treatment (six with weight loss >5% and 11 with weight loss
- Published
- 2008
37. Diastolic dysfunction and abnormalities of the microcirculation in type 2 diabetes
- Author
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B. Franjic, David S. Celermajer, Dennis K. Yue, Stephen M. Twigg, Belinda A. Brooks, K. Swaraj, and C. R. Ban
- Subjects
Male ,medicine.medical_specialty ,Endothelium ,Endocrinology, Diabetes and Metabolism ,Blotting, Western ,Diastole ,Type 2 diabetes ,Ventricular Dysfunction, Left ,Endocrinology ,Diabetes mellitus ,Internal medicine ,Diabetic cardiomyopathy ,Internal Medicine ,medicine ,Humans ,Endothelial dysfunction ,Echocardiography, Doppler, Pulsed ,business.industry ,Microcirculation ,Connective Tissue Growth Factor ,Case-control study ,Middle Aged ,medicine.disease ,CTGF ,medicine.anatomical_structure ,Diabetes Mellitus, Type 2 ,Case-Control Studies ,Female ,Endothelium, Vascular ,business ,Blood Flow Velocity ,Diabetic Angiopathies - Abstract
Aim: Diabetic cardiomyopathy is an increasingly recognized entity. The pathogenic factors that may contribute to its development, especially the earliest changes of diastolic dysfunction (DD), have not been clearly defined. Microvessel dysfunction and upregulation of profibrotic growth factors have been described as possible causes. The aim of this study was therefore to determine whether microvascular dysfunction and/or upregulation of the profibrotic connective tissue growth factor (CTGF) are associated with subclinical DD in subjects with type 2 diabetes. Methods: Forty subjects with type 2 diabetes and 20 age-matched non-diabetic controls, all of whom had no clinical evidence of ischaemic heart disease, cardiac failure or echo evidence of systolic ventricular dysfunction, were recruited. Microvascular function was measured by laser Doppler velocimetry, with examination of endothelium-dependent increase in blood flow following iontophoresis of acetylcholine (ACh) and endothelium-independent increase in blood flow in response to the nitric oxide donor sodium nitroprusside (SNP). CTGF levels were determined by Western immunoblotting. Results: DD determined on the basis of traditional echocardiographic criteria was similar in diabetic subjects compared with controls (28 vs. 20%, p = 0.5). Using left ventricular myocardial tissue Doppler-based indices for DD, the E/E′ and the E′/A′ ratios (where E is the flow related to early ventricular filling and E′ and A′ are early and late diastolic velocities, respectively) in diabetic subjects revealed evidence of more DD than controls (p = 0.046 and p = 0.007 respectively) . Comparing controls with no DD by conventional echocardiographic criteria (Group I), diabetes and no DD (Group II) and diabetes with DD (Group III), there was a significant trend in reduction of both endothelium-dependent (ACh fold change; p = 0.04) and endothelium-independent (SNP fold change; p = 0.0004) blood flow across the groups. The ACh and SNP responses, however, were not correlated significantly with quartiles of the E/E′ ratio or the E′/A′ ratio. CTGF plasma levels did not differ across the groups and CTGF did not correlate with parameters of microvascular function. Conclusions: This study indicates that while there is a significant association between DD and measures of microvascular function, the relationship between endothelial dysfunction, CTGF and subtle measures of DD is not strong. Other factors are therefore likely to play an important role in the early pathogenesis of subclinical cardiac DD in type 2 diabetes.
- Published
- 2008
38. Determinants of coronary arterial flow-mediated dilatation following percutaneous coronary intervention
- Author
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Brian P. Bailey, David S. Celermajer, Panuratn Thanyasiri, Michele McGrady, and Mark Raymond Adams
- Subjects
Male ,medicine.medical_specialty ,Endothelium ,medicine.medical_treatment ,Coronary Angiography ,Severity of Illness Index ,Cohort Studies ,Coronary artery disease ,Reference Values ,Coronary Circulation ,Internal medicine ,Diabetes mellitus ,Angioplasty ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Angioplasty, Balloon, Coronary ,Vascular Patency ,Probability ,Analysis of Variance ,business.industry ,Coronary Stenosis ,Mean Vessel Diameter ,Percutaneous coronary intervention ,General Medicine ,Middle Aged ,medicine.disease ,Survival Rate ,Coronary arteries ,Treatment Outcome ,medicine.anatomical_structure ,Case-Control Studies ,Multivariate Analysis ,Cardiology ,Female ,Vascular Resistance ,Endothelium, Vascular ,Cardiology and Cardiovascular Medicine ,business ,Blood Flow Velocity ,Dyslipidemia ,Follow-Up Studies - Abstract
Objective: It has previously been observed that coronary diameter may increase following relief of flow-limiting obstruction. Flow mediated dilatation (FMD) is a fundamental adaptive mechanism for arteries, which is dependent on intact endothelial function. We thus aimed to characterize whether the degree of this flow-mediated dilatation was related to risk factors, which may impair endothelial function. Design: We measured coronary diameter with quantitative angiography before and after relief of chronic total or subtotal (≥99%) occlusion in 171 patients, in which TIMI-0 or TIMI-1 flow was rapidly restored to TIMI-3 (with attendant increase in flow hypothesized to result in FMD). Patients: Of the 171 patients, 73% were male, 62% were current or ex-smokers, 47% were diabetic, 53% had hypertension, 64% had dyslipidemia (documented hypercholesterolemia or total cholesterol >5.0 mg/dL) and 65% were taking statin therapy. Results: Mean vessel diameter was 2.8 ± 0.7 mm and flow-mediated dilatation measured 15.1% ± 20.1% in target vessel, compared with 1.6 ± 3.1 in control vessels (P < 0.05). FMD was strongly and inversely related to baseline vessel diameter (r = −0.48, P < 0.001). The degree of vessel dilation correlated negatively with the presence of diabetes (r = −0.33, P < 0.001), smoking (r = −0.30, P < 0.001) and extent of coronary artery disease (CAD, r = −0.17, P = 0.01) and positively with the use of statins (r = 0.27, P = 0.001). These factors, apart from extent of CAD, remained significant predictors of FMD on multivariate analysis. Conclusions: FMD occurs in human coronary arteries following restoration of flow. The magnitude of FMD appears related to vascular risk factors and their treatment. © 2008 Wiley-Liss, Inc.
- Published
- 2008
39. Characteristics of cardiac and vascular structure and function in Prader?Willi syndrome
- Author
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David S. Celermajer, Georgina Loughnan, Katharine Steinbeck, Sanjay Patel, Jason A. Harmer, and Michael R. Skilton
- Subjects
Adult ,Blood Glucose ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Adolescent ,Brachial Artery ,Endocrinology, Diabetes and Metabolism ,Cardiovascular System ,Sudden death ,Sudden cardiac death ,Coronary artery disease ,Endocrinology ,Risk Factors ,Interquartile range ,medicine.artery ,Internal medicine ,Humans ,Insulin ,Medicine ,Plethysmograph ,Prospective Studies ,Radial artery ,Brachial artery ,Prospective cohort study ,Exercise Tolerance ,business.industry ,nutritional and metabolic diseases ,medicine.disease ,Plethysmography ,Vasodilation ,C-Reactive Protein ,Carotid Arteries ,Death, Sudden, Cardiac ,Regional Blood Flow ,Case-Control Studies ,Heart Function Tests ,Radial Artery ,Female ,business ,Prader-Willi Syndrome ,Biomarkers - Abstract
Summary Objective Prader–Willi syndrome (PWS) is a genetic obesity syndrome characterized by hyperphagia, behavioural disturbance and intellectual disability. PWS appears to be associated with a high incidence of sudden death, suspected to be cardiopulmonary in origin. We therefore sought to provide an assessment of cardiac and vascular structure and function in patients with PWS. Patients Nine patients with genetically confirmed PWS, mean age 28 years, body mass index (BMI) 42 kg/m2, were compared with nine age- and gender-matched lean controls. Measurements Lipid parameters, high-sensitivity C-reactive protein (hs-CRP) and fasting glucose and insulin were measured. To assess cardiac structure and function, a resting electrocardiogram (ECG), exercise stress test, 24-h continuous ECG monitoring, and echocardiogram were obtained. Patients and control subjects also underwent comprehensive noninvasive vascular assessment, including venous-occlusion forearm plethysmography, brachial artery flow-mediated dilatation (FMD), radial artery tonometry and carotid intima–media thickness (IMT) measurements. Results All patients with PWS had significantly elevated hs-CRP (> 3·0 mg/l) (mean 11·5 mg/l, median 11·47, interquartile range: 4·48–15·8 mg/l), compared with controls (P
- Published
- 2007
40. Pathophysiological levels of the obesity related peptides resistin and ghrelin increase adhesion molecule expression on human vascular endothelial cells
- Author
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Michael R. Skilton, Ian D. Caterson, Daniel P Sieveking, Shirley Nakhla, and David S. Celermajer
- Subjects
Leptin ,medicine.medical_specialty ,Time Factors ,Physiology ,Peptide Hormones ,medicine.medical_treatment ,Vascular Cell Adhesion Molecule-1 ,Enzyme-Linked Immunosorbent Assay ,Biology ,Monocytes ,Physiology (medical) ,Internal medicine ,Cell Adhesion ,medicine ,Humans ,Insulin ,Resistin ,Cell adhesion ,Cells, Cultured ,Pharmacology ,Dose-Response Relationship, Drug ,Cell adhesion molecule ,Soluble cell adhesion molecules ,Endothelial Cells ,Adhesion ,Intercellular Adhesion Molecule-1 ,Ghrelin ,Endocrinology ,E-Selectin ,Cell Adhesion Molecules ,hormones, hormone substitutes, and hormone antagonists - Abstract
SUMMARY 1. In the present study, we sought to determine whether physiological or pathophysiological concentrations of obesity related peptides influence the key early atherogenic events of monocyte adhesion to endothelial cells and adhesion molecule expression using primary human cells. 2. Human umbilical vein endothelial cells were grown to confluence and human monocytes were obtained by elutriation. Adhesion was assessed by automated cell counting and cell adhesion molecule expression (E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)) was assayed by ELISA. 3. Experimental conditions included untreated control, ghrelin (100, 150, 450 and 1350 pmol/L), resistin (15, 40 and 100 ng/mL) and combined leptin and insulin (combinations of 30 and 120 pmol/L insulin and 5, 50 and 500 ng/mL leptin). 4. Both resistin and ghrelin produced modest but significant increases in VCAM-1 expression (110 ± 4 and 117 ± 13% compared with controls, respectively; both P ≤ 0.01). Ghrelin also increased ICAM-1 expression (119 ± 17% of control; P ≤ 0.01). 5. However, despite these increases in adhesion molecule expression, neither ghrelin nor resistin altered monocyte adhesion values. 6. Neither leptin nor insulin altered monocyte adhesion to endothelial cells or cell adhesion molecule expression. 7. Pathophysiologically relevant concentrations of ghrelin and resistin, within the range of concentrations exhibited by patients with anorexia nervosa or the Prader–Willi syndrome and type 2 diabetes, respectively, increase endothelial cell adhesion molecule expression, possibly contributing to increased atherosclerosis risk in such subjects.
- Published
- 2005
41. Beauty is in the eye of the examiner: reaching agreement about physical signs and their value
- Author
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David S. Celermajer, Anthony M. Joshua, and Martin R. Stockler
- Subjects
Value (ethics) ,Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Sick role ,media_common.quotation_subject ,education ,Physical examination ,Evidence-based medicine ,Affect (psychology) ,Beauty ,Internal Medicine ,medicine ,Optometry ,Clinical competence ,business ,Reliability (statistics) ,media_common - Abstract
Despite advances in other areas, evidence-based medicine is yet to make substantial inroads on the standard medical physical examination. We have reviewed the evidence about the accuracy and reliability of the physical examination and common clinical signs. The physical examination includes many signs of marginal accuracy and reproducibility. These may not be appreciated by clinicians and could adversely affect decisions about treatment and investigations or the teaching and examination of students and doctors-in-training. We provide a selected summary of the reliability and accuracy as well as important messages of key findings in the physical examination.
- Published
- 2005
42. Androgen receptor gene expression in leucocytes is hormonally regulated: implications for gender differences in disease pathogenesis
- Author
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Alison K. Death, David J. Handelsman, Mark A. Sader, David S. Celermajer, Kristine C.Y. McGrath, Mark Jimenez, Michelle D. Hill, and Kenneth F. Bradstock
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Biology ,Gonadotropin-Releasing Hormone ,Mice ,Prostate cancer ,Endocrinology ,Internal medicine ,Androgen deficiency ,medicine ,Animals ,Humans ,Testosterone ,Gonadal Steroid Hormones ,Aged ,Aged, 80 and over ,Estradiol ,Middle Aged ,Androgen ,medicine.disease ,Mice, Mutant Strains ,Androgen receptor ,Cardiovascular Diseases ,Receptors, Androgen ,Case-Control Studies ,Dihydrotestosterone ,Disease Progression ,Leukocytes, Mononuclear ,Female ,Androgen replacement therapy ,Hormone ,medicine.drug - Abstract
Summary Objective There is evidence that male sex hormones influence the rate of progression of inflammatory and cardiovascular diseases. We have previously shown that human leucocytes and arterial cells isol- ated from male donors express more androgen receptor (AR) than those from female cells, with potentially pro-atherogenic effects. We now investigate whether the gender difference in AR expression is due to genetic or hormonal regulation. Design and Patients The influence of hormones on AR expression were studied in hpg mice (a mouse model of androgen deficiency) treated with testosterone, oestradiol or dihydrotestosterone (DHT). Blood samples were obtained for leucocyte AR expression and hormone levels from 53 subjects, grouped into: 12 male (six young adult (27- 45 years), six elderly (71-79 years)) and six female (young adult 25 - 45 years) healthy controls; six male-to-female transsexuals (M2F; 20 - 50 years) receiving stable pharmacological oral oestrogen treatment; six female-to-male transsexuals (F2M; 31 - 51 years) receiving stable androgen replacement therapy; five younger men (18 - 56 years) who had been receiving long-term androgen replace- ment therapy for hypogonadal disease; six elderly men (72 - 88 years) who had undergone medical castration for prostate cancer treatment; and 12 male bone marrow transplant recipients (BMT; 23 - 65 years) from either male or female donors. Measurements Serum testosterone and oestradiol concentrations were measured by established immunoflurometric assays from un- extracted human serum. AR mRNA levels were measured by RT-PCR and AR protein levels by western blot (cell culture) or immuno- histochemistry (mouse arteries). Results We found that AR mRNA levels were significantly down- regulated in the leucocytes of hpg mice that were treated with exogenous testosterone, oestradiol or DHT. AR protein levels were also lower in aortic tissue from the same mice. In humans, we found AR expression was significantly down-regulated by exogenous treatment with testo- sterone in F2M (31 ± 13%, compared with control) or oestradiol in M2F (22 ± 5%) but was significantly up-regulated by endogenous testosterone in BMT (128 ± 17%). Low androgen levels measured in castrated older men were associated with markedly increased AR expression (207 ± 26%, P < 0·05) compared with age-matched older male controls (100 ± 2%). Conclusions Our results indicate a regulated ability of vascular cells to respond to sex hormones, with the effects of exogenous therapies differing markedly from those due to endogenous sex hormones. We conclude that the gender difference in AR expression in vascular cells is hormonally, rather than genetically, controlled.
- Published
- 2005
43. Physiological testosterone replacement and arterial endothelial function in men
- Author
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Mark A. Sader, David S. Celermajer, Michael R. Skilton, Susan M. Wishart, David J. Handelsman, and Kaye A. Griffiths
- Subjects
medicine.medical_specialty ,Endothelium ,medicine.drug_class ,business.industry ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Androgen ,Hyperaemia ,Endocrinology ,Blood pressure ,medicine.anatomical_structure ,Internal medicine ,Dilator ,cardiovascular system ,medicine ,Androgen replacement therapy ,medicine.symptom ,business ,Blood vessel ,Artery - Abstract
Summary objective The vascular effects of fluctuations in testosterone levels within the physiological range in otherwise healthy men are not known. We therefore aimed to study arterial function in hypogonadal men receiving long-term physiological androgen replacement therapy, at trough and peak testosterone levels. patients and design We recruited nine hypogonadal men (aged 35 ± 4 years) receiving androgen replacement therapy, each treated with 800 mg testosterone (T) depot preparations every 6 months. measurements Serum lipid and hormone levels and arterial reactivity were measured, prior to (trough T) and 2–4 weeks following testosterone administration (peak T). Each subject therefore served as their own control. Vessel diameter was measured by ultrasound at rest, during reactive hyperaemia [leading to flow-mediated dilatation (FMD), an endothelium-dependent response] and after sublingual nitroglycerin (GTN, an endothelium-independent dilator). results Serum T (13 ± 2 nmvs. 27 ± 3 nm for trough and peak serum T, respectively, P 0·2). Lipid, blood pressure and vessel diameter measurements were also similar before and after testosterone administration. conclusion Physiological replacement of testosterone is associated with decreased endothelium-dependent dilatation, in hypogonadal men.
- Published
- 2003
44. Quantifying right atrial filling and emptying: A 4D-flow MRI study
- Author
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Fraser M. Callaghan, Clare Arnott, Gemma A. Figtree, Shelby Kutty, David S. Celermajer, and Stuart M. Grieve
- Subjects
Radiology, Nuclear Medicine and imaging - Published
- 2017
45. Oestradiol improves arterial endothelial function in healthy men receiving testosterone
- Author
-
Mark A. Sader, Kaye A. Griffiths, David S. Celermajer, Robyn J. McCredie, David J. Handelsman, and Susan M. Wishart
- Subjects
medicine.medical_specialty ,education.field_of_study ,Endothelium ,medicine.drug_class ,business.industry ,Endocrinology, Diabetes and Metabolism ,Population ,Hyperaemia ,Endocrinology ,medicine.anatomical_structure ,Estrogen ,Internal medicine ,medicine.artery ,Dilator ,medicine ,Brachial artery ,medicine.symptom ,education ,business ,Testosterone ,Hormone - Abstract
OBJECTIVE To assess prospectively the effects of low dose oestradiol on arterial endothelial and smooth muscle function in healthy men. Oestrogen use is associated with reduced cardiovascular disease in oestrogen-deficient women, however, the vascular effects of low-dose oestradiol in healthy men have not been investigated previously. PATIENTS and DESIGN Twenty-three men (aged 32 ± 8 years) were randomized to receive depot implants of testosterone (T) alone (group 1, n = 10), or T with either 10 mg (group 2, n = 7) or 20 mg (group 3, n = 6) of oestradiol (E). MEASUREMENTS Hormone levels, lipids and vascu-lar reactivity were measured before, 1 month and 6 months after hormone implantation. Using high-resolution ultrasound, brachial artery diameter was measured at rest, during reactive hyperaemia (leading to flow-mediated dilatation, FMD, which is endothelium-dependent) and after sublingual nitroglycerin (GTN, an endothelium-independent dilator). RESULTS Oestradiol produced a dose-dependent increase in plasma oestradiol (at 1 month 96 ± 7, 149 ± 6, 192 ± 23 pmol/l in the 3 groups, respec-tively, P
- Published
- 2001
46. Research Methods in Human Cardiovascular Pharmacology edited by Dr S. Maxwell and Prof. D. WebbFlow-mediated dilatation
- Author
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David S. Celermajer and Olli T. Raitakari
- Subjects
Pharmacology ,medicine.medical_specialty ,Endothelium ,Vascular disease ,business.industry ,Vasodilation ,Arteriosclerosis ,medicine.disease ,Coronary arteries ,medicine.anatomical_structure ,Endocrinology ,Internal medicine ,medicine ,Cardiology ,Pharmacology (medical) ,Endothelial dysfunction ,business ,Coronary atherosclerosis ,Artery - Abstract
Arterial endothelial dysfunction is one of the key early events in atherogenesis, preceding structural atherosclerotic changes. It is also important in the late stages of obstructive atherosclerosis, predisposing to constriction and/or thrombosis. Endothelial function can be measured in coronary arteries and in the periphery by measuring vasomotor function after intra-arterial infusion of pharmacologic substances which enhance the release of endothelial nitric oxide. The disadvantage of these methods is their invasive nature, which generally makes them unsuitable for studies involving asymptomatic subjects. For this reason, noninvasive tests of endothelial function have been developed. In the most widely used of these, an ultrasound-based method, arterial diameter is measured in response to an increase in shear stress, which causes endothelium-dependent dilatation. Endothelial function assessed by this method correlates with invasive testing of coronary endothelial function, as well as with the severity and extent of coronary atherosclerosis. This noninvasive endothelial function testing has provided valuable insights into early atherogenesis, as well as into the potential reversibility of endothelial dysfunction by various strategies, including pharmacological agents (lipid lowering, ACE inhibition), l-arginine, antioxidants and hormones.
- Published
- 2000
47. Hormone replacement therapy is associated with improved arterial physiology in healthy post-menopausal women
- Author
-
Jacqui Robinson, David S. Celermajer, Mavis Abbey, Robyn J. McCredie, Anne Pike, Mark R. Adams, Anthony C. Keech, and Jane McCrohon
- Subjects
Adult ,medicine.medical_specialty ,Adolescent ,Brachial Artery ,Endothelium ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Hysterectomy ,Hyperaemia ,Endocrinology ,Internal medicine ,medicine.artery ,medicine ,Humans ,Brachial artery ,Progesterone ,Aged ,Ultrasonography ,business.industry ,Estrogen Replacement Therapy ,Estrogens ,Hormone replacement therapy (menopause) ,Middle Aged ,medicine.disease ,Postmenopause ,Vasodilation ,Menopause ,Cross-Sectional Studies ,medicine.anatomical_structure ,Cardiovascular Diseases ,Regional Blood Flow ,Estrogen ,Female ,Endothelium, Vascular ,medicine.symptom ,business ,Artery - Abstract
OBJECTIVE Oestrogen replacement therapy is associated with a marked reduction in coronary event rates in post-menopausal women. As older age is associated with progressive arterial endothelial damage, a key event in atherosclerosis, we assessed whether hormone replacement therapy (HRT) with oestrogen alone, or oestrogen and progesterone combined, is associated with improved endothelial function in healthy women after the menopause. DESIGN Using high resolution external vascular ultrasound, brachial artery diameter was measured at rest and in response to reactive hyperaemia, with increased flow causing endothelium-dependent dilatation (flow-mediated dilatation). PATIENTS We investigated 135 healthy women; 40 were pre-menopausal (mean +/- SD age/26 +/- 6 years, group 1), 40 were post-menopausal and had never taken HRT (aged 58 +/- 3 years; group 2) and 55 were age-matched post-menopausal women who had taken HRT for > or = 2 years, from within 2 years of the menopause (aged 57 +/- 4 years; group 3). In group 3, 40 women were on combined oestrogen and progesterone and 15 on oestrogen-only HRT. RESULTS In group 2, flow-mediated dilatation was significantly reduced compared with group 1 (4.4 +/- 3.4 vs 9.6 +/- 3.6%, P < 0.001), consistent with a decline in arterial endothelial function after the menopause. In group 3, however, flow-mediated dilatation was significantly better than group 2 (6.2 +/- 3.3 vs 4.4 +/- 3.4%, P = 0.01), suggesting a protective effect of HRT. Flow-mediated dilatation was similar in women taking oestrogen alone and in those on combined HRT (5.5 +/- 2.8 vs 6.5 +/- 3.4%, P = 0.40). CONCLUSIONS Long-term HRT is associated with improved arterial endothelial function in healthy post-menopausal women. This benefit was observed in both the combined hormone replacement and unopposed oestrogen therapy groups. This may explain some of the apparent cardioprotective effect of HRT after the menopause.
- Published
- 1996
48. At medium term follow-up (3.4 ± 2.4 years, range two months to eight years) there was one late death in each group, and seven patients in each group had return of angina or congestive heart failure. Twenty-one patients in the emergency group and 22 patien
- Author
-
David S. Celermajer, R. Beetson, G. E. Zeng, Clifford F. Hughes, Brian P. Bailey, and Louis Bernstein
- Subjects
Angina ,medicine.medical_specialty ,business.industry ,Group (periodic table) ,Range (biology) ,Heart failure ,Internal Medicine ,medicine ,cardiovascular diseases ,medicine.disease ,business ,Surgery ,Medium term - Published
- 1991
49. Author reply
- Author
-
David S. Celermajer and Low Aj
- Subjects
Psychoanalysis ,business.industry ,Internal Medicine ,Medicine ,business - Published
- 2013
50. Leukocyte androgen receptor expression in mice and men; Gender and hormonal regulation, and implications for atherosclerosis
- Author
-
Alison K. Death, David J. Handelsman, Mark A. Sader, David S. Celermajer, and Kristine C.Y. McGrath
- Subjects
Pulmonary and Respiratory Medicine ,Androgen receptor ,medicine.medical_specialty ,Endocrinology ,Expression (architecture) ,business.industry ,Internal medicine ,Medicine ,Cardiology and Cardiovascular Medicine ,business ,Hormone - Published
- 2003
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