A Dart | London Metropolitan University (original) (raw)

Papers by A Dart

Heart, Lung and Circulation

Global Spine Journal

Introduction Intervertebral disc degeneration (IVDD) is implicated in 40% of low back pain (LBP) ... more Introduction Intervertebral disc degeneration (IVDD) is implicated in 40% of low back pain (LBP) cases. A total of 80% of people will be affected by LBP some time in their lifetime. LBP has a considerable socioeconomic impact, costed at 100billionintheUnitedStatesin2006and100 billion in the United States in 2006 and 100billionintheUnitedStatesin2006and9.17 billion in Australia in 2001. LBP was designated a National Health Priority in Australia in 2009. Current options for the treatment of IVDD is by surgical intervention (spinal fusion) no disease modifying drug treatments are currently available. Recent studies suggest that mesenchymal stem cells (MSCs) offer therapeutic promise in IVDD, preclinical studies. In the present study, we have examined the efficacy of bone marrow derived mesenchymal stem cells (BMMSCs) for the treatment of IVDD in an ovine large animal model of IVDD.1 Materials and Methods A single pool of heterologous ovine BMMSCs was isolated and culture expanded up to passage 8. These BMMSCs were CD44 and CD106 +ve and CD34, CD45 and CD...

Computational and structural biotechnology journal, 2014

Atherosclerotic plaques develop at particular sites in the arterial tree, and this regional local... more Atherosclerotic plaques develop at particular sites in the arterial tree, and this regional localisation depends largely on haemodynamic parameters (such as wall shear stress; WSS) as described in the literature. Plaque rupture can result in heart attack or stroke and hence understanding the development and vulnerability of atherosclerotic plaques is critically important. The purpose of this study is to characterise the haemodynamics of blood flow in the mouse aortic arch using numerical modelling. The geometries are digitalised from synchrotron imaging and realistic pulsatile blood flow is considered under rigid wall assumptions. Two cases are considered; arteries with and without plaque. Mice that are fed under fat diet present plaques in the aortic arch whose size is dependent on the number of weeks under the diet. The plaque distribution in the region is however relatively constant through the different samples. This result underlines the influence of the geometry and consequent...

American Journal of Hypertension, 2005

Background: Several new techniques exist for measuring arterial stiffness, but their association ... more Background: Several new techniques exist for measuring arterial stiffness, but their association with central pulse wave velocity (PWV), an established measure of central arterial stiffness, has not been compared in the same study. The aim of this study was to compare the agreement of the new techniques with central PWV. Methods: Fifteen men with coronary artery disease (59 Ϯ 2 years of age) and 15 healthy men (28 Ϯ 1 years of age) were recruited. The following measures were performed in a random sequence and repeated after 1 week: central and distal pulse wave velocity (PWV), large and small artery compliance (C1 and C2, respectively), and stroke volume/pulse pressure (SV/PP) (measured by HDI/ PulseWave CR-2000), augmentation index (AIx) and central pulse pressure (CPR) (Sphygmocor), stiffness index (SI) (Micro Medical Pulse Trace), systemic arterial compliance (SAC) (area method), and brachial PP (Dinamap). Methods were compared using correlation coefficients and Bland-Altman analysis. Results: Although all measures of arterial stiffness except PWV correlated significantly with central PWV (P Ͻ .01 for each), Bland-Altman analysis showed poor agreement (confidence interval [CI] Ͼ3 Z-scores) between central PWV and C1, C2, SV/PP, and SAC). There was good agreement (CI Ͼ 2 Z-scores) between central PWV and SI, AIx, CPP, and brachial PP. The coefficient of variation was lowest with central PWV (7.6%), brachial PP (8.0%), and SV/PP (8.6%) and was significantly higher (P Ͻ .05) in increasing order with C1 (11.3%), C2 (15.6%), SI (17.8%), SAC (19.3%), AIx (22.4%), and CPP (25.3%). Conclusions: Based on our study findings, C1, C2, SV/PP, and SAC show poor agreement with central PWV, an established measure of central arterial stiffness. Indices of this type should therefore be useful in providing a more complete understanding of arterial stiffness. In comparison, SI, AIx, and CPP are more closely related to central arterial stiffness.

Canadian Journal of Kidney Health and Disease, 2014

Background: Nephrotic syndrome is a commonly acquired kidney disease in children that causes sign... more Background: Nephrotic syndrome is a commonly acquired kidney disease in children that causes significant morbidity due to recurrent episodes of heavy proteinuria. The management of childhood nephrotic syndrome is known to be highly variable among physicians and care centres. Objectives: The primary objective of the study is to determine centre-, physician-, and patient-level characteristics associated with steroid exposure and length of steroid treatment. We will also determine the association of dose and duration of steroid treatment and time to first relapse as a secondary aim. An embedded qualitative study utilizing focus groups with health care providers will enrich the quantitative results by providing an understanding of the attitudes, beliefs and local contextual factors driving variation in care. Design: Mixed-methods study; prospective observational cohort (quantitative component), with additional semi-structured focus groups of healthcare professionals (qualitative compone...

Hypertension, 2001

The mechanisms relating pulse pressure to cardiovascular outcome may include surrogacy for corona... more The mechanisms relating pulse pressure to cardiovascular outcome may include surrogacy for coronary disease severity. Although pulse pressure is typically measured at the brachial artery, central pulse pressure and its principal determinant, large-artery stiffness, may relate more closely to disease severity. This study aimed to determine the relationships between large-artery stiffness and carotid and brachial blood pressures and coronary artery disease severity. One hundred fourteen male patients with coronary artery disease (age 60±8 years, mean±SD) and 57 age-matched healthy male controls (age 59±9 years) were recruited. Patients were classified into 2 groups based on the magnitude of their maximum coronary stenosis: moderate (50% to 89%) and severe (≥90%). Large-artery stiffness was assessed as systemic arterial compliance and carotid-femoral pulse wave velocity. Mean pressure was not different between the 3 groups. Systemic compliance and carotid pulse pressure were significan...

Hypertension, 2001

It is widely accepted that in women, estrogens provide protection against the development of card... more It is widely accepted that in women, estrogens provide protection against the development of cardiovascular disease. However, the cardiovascular role of estrogens in men remains uncertain, despite preliminary evidence that endogenous estrogens produced by aromatization of androgenic precursors are of physiological importance. Hypogonadal men have very low levels of circulating estrogen. We studied the responsiveness of forearm resistance arteries to vasoconstrictor and vasodilator agents in 12 men (mean±SEM age, 68.7±2.6 years) rendered hypogonadal as a result of treatment for prostatic cancer, before and after 8 weeks of estrogen supplementation (estradiol valerate 1 mg daily; n=7) or placebo (n=5). Forearm blood flow was measured by venous occlusion plethysmography, and vasoactive agents were infused through a brachial artery cannula in doses that did not affect blood pressure or heart rate. Estrogen supplementation was well tolerated, with no adverse effects. After estrogen treat...

Heart, Lung and Circulation, 2013

Heart, Lung and Circulation, 2013

Heart, Lung and Circulation, 2010

Heart, Lung and Circulation, 2012

Heart, Lung and Circulation, 2012

P = 0.001) and glycoprotein 2b3a inhibitors (34.7% vs 46.6%, P = 0.002) were less in the female c... more P = 0.001) and glycoprotein 2b3a inhibitors (34.7% vs 46.6%, P = 0.002) were less in the female cohort. There was no difference in door to balloon times (79 min vs 78 min, P = 0.60) or in-patient mortality (females 6.7%, males 5.1%, P = 0.64). Conclusions: Demographic and procedural differences are evident between the genders. These do not appear to impact on outcome, in particular no effect on D2BT or inpatient mortality was noted.

Heart, Lung and Circulation, 2011

Heart, Lung and Circulation, 2011

Background: Obesity has been associated with the development of atrial fibrillation (AF); however... more Background: Obesity has been associated with the development of atrial fibrillation (AF); however the mechanisms by which it results in a pro-arrhythmic substrate remain unknown. Methods: Thirty sheep were studied at baseline, four months and eight months, following an ad libitum calorie dense diet. Ten were sampled at each time point for cardiac MRI, invasive haemodynamic evaluation (left atrial and arterial pressure) and detailed electrophysiologic study. An additional six maintenance-fed control sheep were sampled at four and eight months to control for time/age-related effects. A custom made 128-electrode plaque applied to the right and left atria was used to quantify; bi-atrial effective refractory periods (ERP); conduction velocity (CV); conduction heterogeneity index (CHI) at four pacing cycle lengths (PCL) from four sites; and AF inducibility. Quantitative myocardial histology was performed for myocardial fibrosis, inflammation and lipidosis. Results: Weight increased from 58 ± 7 kg to 77 ± 5 kg to 105 ± 13 kg (P < 0.001). With increasing weight there was: progressive decrement in atrial CV (P = 0.01), increasing atrial volumes (P = 0.01), atrial fibrosis (P = 0.007) and lipidosis (P = 0.049). There was regional variation in conduction heterogeneity (P = 0.04) with increasing weight. Electrophysiologic disturbances persisted after adjusting for haemodynamic variables. No changes were observed in the control cohort (ERP; P = 0.5, CV; P = 0.8, CHI; P = 0.9). With increasing adiposity, AF event number (P = 0.001) and duration (P < 0.001) significantly increased. No significant change was observed in ERP with increasing adiposity (P = 0.198). Conclusion: Obesity induces early and progressive atrial structural and electrophysiological remodelling. These electrophysiological abnormalities were independent of adverse haemodynamic changes and occurred with a step-wise increase in AF burden.

Heart, Lung and Circulation, 2011

Diabetes, 2009

OBJECTIVE Chronic low-grade activation of the immune system (CLAIS) predicts type 2 diabetes via ... more OBJECTIVE Chronic low-grade activation of the immune system (CLAIS) predicts type 2 diabetes via a decrease in insulin sensitivity. Our study investigated potential relationships between nuclear factor-κB (NF-κB) and c-Jun NH2-terminal kinase (JNK) pathways—two pathways proposed as the link between CLAIS and insulin resistance. RESEARCH DESIGN AND METHODS Adiposity (dual-energy X-ray absorptiometry), waist-to-hip ratio (WHR), and insulin sensitivity (M, hyperinsulinemic-euglycemic clamp) were measured in 22 healthy nondiabetic volunteers (aged 29 ± 11 years, body fat 28 ± 11%). NF-κB activity (DNA-binding assay) and JNK1/2 activity (phosphorylated JNK) were assessed in biopsies of the vastus lateralis muscle and subcutaneous adipose tissue and in peripheral blood mononuclear cell (PBMC) lysates. RESULTS NF-κB activities in PBMCs and muscle were positively associated with WHR after adjustment for age, sex, and percent body fat (both P < 0.05). NF-κB activity in PBMCs was inversely...

Circulation, 1992

BACKGROUND Measurement of cardiac norepinephrine spillover may indicate the amount of transmitter... more BACKGROUND Measurement of cardiac norepinephrine spillover may indicate the amount of transmitter at neuroeffector sites but does not distinguish neuronal release or reuptake in determining this amount or provide information about other aspects of sympathetic function. This report examines how cardiac spillover of the norepinephrine metabolite dihydroxyphenylglycol (DHPG) provides additional distinct information about cardiac sympathetic function. METHODS AND RESULTS Arterial and coronary venous blood samples were taken during cardiac catheterization and intravenous infusion of [3H]norepinephrine in 57 subjects. Subjects were given intravenous yohimbine or underwent mental stress, handgrip exercise, and cycling exercise to activate sympathetic nerves or were given intravenous desipramine to block norepinephrine reuptake. Cardiac DHPG spillover (601 +/- 41 pmol/min) was eightfold greater than norepinephrine spillover (78 +/- 10 pmol/min) at rest and increased during sympathetic activ...

Cardiovascular Research, 2005

Heart, Lung and Circulation

Global Spine Journal

Introduction Intervertebral disc degeneration (IVDD) is implicated in 40% of low back pain (LBP) ... more Introduction Intervertebral disc degeneration (IVDD) is implicated in 40% of low back pain (LBP) cases. A total of 80% of people will be affected by LBP some time in their lifetime. LBP has a considerable socioeconomic impact, costed at 100billionintheUnitedStatesin2006and100 billion in the United States in 2006 and 100billionintheUnitedStatesin2006and9.17 billion in Australia in 2001. LBP was designated a National Health Priority in Australia in 2009. Current options for the treatment of IVDD is by surgical intervention (spinal fusion) no disease modifying drug treatments are currently available. Recent studies suggest that mesenchymal stem cells (MSCs) offer therapeutic promise in IVDD, preclinical studies. In the present study, we have examined the efficacy of bone marrow derived mesenchymal stem cells (BMMSCs) for the treatment of IVDD in an ovine large animal model of IVDD.1 Materials and Methods A single pool of heterologous ovine BMMSCs was isolated and culture expanded up to passage 8. These BMMSCs were CD44 and CD106 +ve and CD34, CD45 and CD...

Computational and structural biotechnology journal, 2014

Atherosclerotic plaques develop at particular sites in the arterial tree, and this regional local... more Atherosclerotic plaques develop at particular sites in the arterial tree, and this regional localisation depends largely on haemodynamic parameters (such as wall shear stress; WSS) as described in the literature. Plaque rupture can result in heart attack or stroke and hence understanding the development and vulnerability of atherosclerotic plaques is critically important. The purpose of this study is to characterise the haemodynamics of blood flow in the mouse aortic arch using numerical modelling. The geometries are digitalised from synchrotron imaging and realistic pulsatile blood flow is considered under rigid wall assumptions. Two cases are considered; arteries with and without plaque. Mice that are fed under fat diet present plaques in the aortic arch whose size is dependent on the number of weeks under the diet. The plaque distribution in the region is however relatively constant through the different samples. This result underlines the influence of the geometry and consequent...

American Journal of Hypertension, 2005

Background: Several new techniques exist for measuring arterial stiffness, but their association ... more Background: Several new techniques exist for measuring arterial stiffness, but their association with central pulse wave velocity (PWV), an established measure of central arterial stiffness, has not been compared in the same study. The aim of this study was to compare the agreement of the new techniques with central PWV. Methods: Fifteen men with coronary artery disease (59 Ϯ 2 years of age) and 15 healthy men (28 Ϯ 1 years of age) were recruited. The following measures were performed in a random sequence and repeated after 1 week: central and distal pulse wave velocity (PWV), large and small artery compliance (C1 and C2, respectively), and stroke volume/pulse pressure (SV/PP) (measured by HDI/ PulseWave CR-2000), augmentation index (AIx) and central pulse pressure (CPR) (Sphygmocor), stiffness index (SI) (Micro Medical Pulse Trace), systemic arterial compliance (SAC) (area method), and brachial PP (Dinamap). Methods were compared using correlation coefficients and Bland-Altman analysis. Results: Although all measures of arterial stiffness except PWV correlated significantly with central PWV (P Ͻ .01 for each), Bland-Altman analysis showed poor agreement (confidence interval [CI] Ͼ3 Z-scores) between central PWV and C1, C2, SV/PP, and SAC). There was good agreement (CI Ͼ 2 Z-scores) between central PWV and SI, AIx, CPP, and brachial PP. The coefficient of variation was lowest with central PWV (7.6%), brachial PP (8.0%), and SV/PP (8.6%) and was significantly higher (P Ͻ .05) in increasing order with C1 (11.3%), C2 (15.6%), SI (17.8%), SAC (19.3%), AIx (22.4%), and CPP (25.3%). Conclusions: Based on our study findings, C1, C2, SV/PP, and SAC show poor agreement with central PWV, an established measure of central arterial stiffness. Indices of this type should therefore be useful in providing a more complete understanding of arterial stiffness. In comparison, SI, AIx, and CPP are more closely related to central arterial stiffness.

Canadian Journal of Kidney Health and Disease, 2014

Background: Nephrotic syndrome is a commonly acquired kidney disease in children that causes sign... more Background: Nephrotic syndrome is a commonly acquired kidney disease in children that causes significant morbidity due to recurrent episodes of heavy proteinuria. The management of childhood nephrotic syndrome is known to be highly variable among physicians and care centres. Objectives: The primary objective of the study is to determine centre-, physician-, and patient-level characteristics associated with steroid exposure and length of steroid treatment. We will also determine the association of dose and duration of steroid treatment and time to first relapse as a secondary aim. An embedded qualitative study utilizing focus groups with health care providers will enrich the quantitative results by providing an understanding of the attitudes, beliefs and local contextual factors driving variation in care. Design: Mixed-methods study; prospective observational cohort (quantitative component), with additional semi-structured focus groups of healthcare professionals (qualitative compone...

Hypertension, 2001

The mechanisms relating pulse pressure to cardiovascular outcome may include surrogacy for corona... more The mechanisms relating pulse pressure to cardiovascular outcome may include surrogacy for coronary disease severity. Although pulse pressure is typically measured at the brachial artery, central pulse pressure and its principal determinant, large-artery stiffness, may relate more closely to disease severity. This study aimed to determine the relationships between large-artery stiffness and carotid and brachial blood pressures and coronary artery disease severity. One hundred fourteen male patients with coronary artery disease (age 60±8 years, mean±SD) and 57 age-matched healthy male controls (age 59±9 years) were recruited. Patients were classified into 2 groups based on the magnitude of their maximum coronary stenosis: moderate (50% to 89%) and severe (≥90%). Large-artery stiffness was assessed as systemic arterial compliance and carotid-femoral pulse wave velocity. Mean pressure was not different between the 3 groups. Systemic compliance and carotid pulse pressure were significan...

Hypertension, 2001

It is widely accepted that in women, estrogens provide protection against the development of card... more It is widely accepted that in women, estrogens provide protection against the development of cardiovascular disease. However, the cardiovascular role of estrogens in men remains uncertain, despite preliminary evidence that endogenous estrogens produced by aromatization of androgenic precursors are of physiological importance. Hypogonadal men have very low levels of circulating estrogen. We studied the responsiveness of forearm resistance arteries to vasoconstrictor and vasodilator agents in 12 men (mean±SEM age, 68.7±2.6 years) rendered hypogonadal as a result of treatment for prostatic cancer, before and after 8 weeks of estrogen supplementation (estradiol valerate 1 mg daily; n=7) or placebo (n=5). Forearm blood flow was measured by venous occlusion plethysmography, and vasoactive agents were infused through a brachial artery cannula in doses that did not affect blood pressure or heart rate. Estrogen supplementation was well tolerated, with no adverse effects. After estrogen treat...

Heart, Lung and Circulation, 2013

Heart, Lung and Circulation, 2013

Heart, Lung and Circulation, 2010

Heart, Lung and Circulation, 2012

Heart, Lung and Circulation, 2012

P = 0.001) and glycoprotein 2b3a inhibitors (34.7% vs 46.6%, P = 0.002) were less in the female c... more P = 0.001) and glycoprotein 2b3a inhibitors (34.7% vs 46.6%, P = 0.002) were less in the female cohort. There was no difference in door to balloon times (79 min vs 78 min, P = 0.60) or in-patient mortality (females 6.7%, males 5.1%, P = 0.64). Conclusions: Demographic and procedural differences are evident between the genders. These do not appear to impact on outcome, in particular no effect on D2BT or inpatient mortality was noted.

Heart, Lung and Circulation, 2011

Heart, Lung and Circulation, 2011

Background: Obesity has been associated with the development of atrial fibrillation (AF); however... more Background: Obesity has been associated with the development of atrial fibrillation (AF); however the mechanisms by which it results in a pro-arrhythmic substrate remain unknown. Methods: Thirty sheep were studied at baseline, four months and eight months, following an ad libitum calorie dense diet. Ten were sampled at each time point for cardiac MRI, invasive haemodynamic evaluation (left atrial and arterial pressure) and detailed electrophysiologic study. An additional six maintenance-fed control sheep were sampled at four and eight months to control for time/age-related effects. A custom made 128-electrode plaque applied to the right and left atria was used to quantify; bi-atrial effective refractory periods (ERP); conduction velocity (CV); conduction heterogeneity index (CHI) at four pacing cycle lengths (PCL) from four sites; and AF inducibility. Quantitative myocardial histology was performed for myocardial fibrosis, inflammation and lipidosis. Results: Weight increased from 58 ± 7 kg to 77 ± 5 kg to 105 ± 13 kg (P < 0.001). With increasing weight there was: progressive decrement in atrial CV (P = 0.01), increasing atrial volumes (P = 0.01), atrial fibrosis (P = 0.007) and lipidosis (P = 0.049). There was regional variation in conduction heterogeneity (P = 0.04) with increasing weight. Electrophysiologic disturbances persisted after adjusting for haemodynamic variables. No changes were observed in the control cohort (ERP; P = 0.5, CV; P = 0.8, CHI; P = 0.9). With increasing adiposity, AF event number (P = 0.001) and duration (P < 0.001) significantly increased. No significant change was observed in ERP with increasing adiposity (P = 0.198). Conclusion: Obesity induces early and progressive atrial structural and electrophysiological remodelling. These electrophysiological abnormalities were independent of adverse haemodynamic changes and occurred with a step-wise increase in AF burden.

Heart, Lung and Circulation, 2011

Diabetes, 2009

OBJECTIVE Chronic low-grade activation of the immune system (CLAIS) predicts type 2 diabetes via ... more OBJECTIVE Chronic low-grade activation of the immune system (CLAIS) predicts type 2 diabetes via a decrease in insulin sensitivity. Our study investigated potential relationships between nuclear factor-κB (NF-κB) and c-Jun NH2-terminal kinase (JNK) pathways—two pathways proposed as the link between CLAIS and insulin resistance. RESEARCH DESIGN AND METHODS Adiposity (dual-energy X-ray absorptiometry), waist-to-hip ratio (WHR), and insulin sensitivity (M, hyperinsulinemic-euglycemic clamp) were measured in 22 healthy nondiabetic volunteers (aged 29 ± 11 years, body fat 28 ± 11%). NF-κB activity (DNA-binding assay) and JNK1/2 activity (phosphorylated JNK) were assessed in biopsies of the vastus lateralis muscle and subcutaneous adipose tissue and in peripheral blood mononuclear cell (PBMC) lysates. RESULTS NF-κB activities in PBMCs and muscle were positively associated with WHR after adjustment for age, sex, and percent body fat (both P < 0.05). NF-κB activity in PBMCs was inversely...

Circulation, 1992

BACKGROUND Measurement of cardiac norepinephrine spillover may indicate the amount of transmitter... more BACKGROUND Measurement of cardiac norepinephrine spillover may indicate the amount of transmitter at neuroeffector sites but does not distinguish neuronal release or reuptake in determining this amount or provide information about other aspects of sympathetic function. This report examines how cardiac spillover of the norepinephrine metabolite dihydroxyphenylglycol (DHPG) provides additional distinct information about cardiac sympathetic function. METHODS AND RESULTS Arterial and coronary venous blood samples were taken during cardiac catheterization and intravenous infusion of [3H]norepinephrine in 57 subjects. Subjects were given intravenous yohimbine or underwent mental stress, handgrip exercise, and cycling exercise to activate sympathetic nerves or were given intravenous desipramine to block norepinephrine reuptake. Cardiac DHPG spillover (601 +/- 41 pmol/min) was eightfold greater than norepinephrine spillover (78 +/- 10 pmol/min) at rest and increased during sympathetic activ...

Cardiovascular Research, 2005