Alexandra Heaton | The University of Western Australia (original) (raw)

Papers by Alexandra Heaton

The proposal that dietary docosahexaenoic acid (DHA) enhances neurocognitive functioning in term ... more The proposal that dietary docosahexaenoic acid (DHA) enhances neurocognitive functioning in term infants is controversial. Theoretical evidence, laboratory research and human epidemiological studies have convincingly demonstrated that DHA deficiency can negatively impact neurocognitive development. However, the results from randomized controlled trials (RCTs) of DHA supplementation in human term-born infants have been inconsistent. This article will (i) discuss the role of DHA in the human diet, (ii) explore the physiological mechanisms by which DHA plausibly influences neurocognitive capacity, and (iii) seek to characterize the optimal intake of DHA during infancy for neurocognitive functioning, based on existing research that has been undertaken in developed countries (specifically, within Australia). The major observational studies and RCTs that have examined dietary DHA in human infants and animals are presented, and we consider suggestions that DHA requirements vary across individuals according to genetic profile. It is important that the current evidence concerning DHA supplementation is carefully evaluated so that appropriate recommendations can be made and future directions of research can be strategically planned.

PURPOSE: Impaired GABAergic inhibition has been implicated in the pathophysiology of epilepsy. Th... more PURPOSE:
Impaired GABAergic inhibition has been implicated in the pathophysiology of epilepsy. The possibility of a paradoxical excitatory effect of GABA in epilepsy has been suggested, but has not been investigated in vivo. We investigated pre- and post-synaptic GABAergic mechanisms in patients with idiopathic generalised epilepsy (IGE).
METHOD:
In 10 patients and 12 control subjects we explored short- and long-interval intracortical inhibition (SICI, LICI; post-synaptic GABAA and GABAB-mediated respectively) and long-interval intracortical facilitation (LICF; pre-synaptic disinhibition) using transcranial magnetic stimulation.

RESULTS:
While post-synaptic GABAB-mediated inhibition was unchanged in IGE (p=0.09), LICF was reduced compared to controls (controls: 141±17% of baseline; untreated patients: 107±12%, p=0.2; treated patients: 79±10%, p=0.003). GABAA-mediated inhibition was reduced in untreated patients (response amplitude 56±4% of baseline vs. 26±6% in controls, p=0.004) and normalised with treatment (37±12%, p=0.5 vs. controls). When measured during LICI, GABAA-mediated inhibition became excitatory in untreated IGE (response amplitude 120±10% of baseline, p=0.017), but not in treated patients.

CONCLUSION:
Pre- and post-synaptic GABA-mediated inhibitory mechanisms are altered in IGE. The findings lend in vivo support to evidence from experimental models and in vitro studies of human epileptic brain tissue that GABA may have a paradoxical excitatory role in ictogenesis.

Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Clinical science (London, England : 1979), 1989

1. A three-step hyperinsulinaemic euglycaemic clamp was performed in six uraemic patients before ... more 1. A three-step hyperinsulinaemic euglycaemic clamp was performed in six uraemic patients before dialysis and after 3 months of treatment with continuous ambulatory peritoneal dialysis, and in seven matched normal control subjects. Glucose turnover was assessed basally and during the clamp using [3-3H]glucose as a tracer. 2. The glucose infusion rate required to maintain euglycaemia was insignificantly higher in normal subjects compared with undialysed uraemic subjects at each insulin infusion rate. 3. The isotopically assessed total glucose turnover was also similar in normal and uraemic subjects. Basal hepatic glucose output was again similar in uraemic and control subjects and output was suppressed to a similar degree at each insulin infusion rate. 4. After treatment with continuous ambulatory peritoneal dialysis, the glucose infusion rate and the total glucose turnover during the clamp rose significantly at all three insulin concentrations (P less than 0.05), but remained insign...

Clinical therapeutics, 2001

Osteoporotic fractures are associated with significant morbidity, mortality, and health care cost... more Osteoporotic fractures are associated with significant morbidity, mortality, and health care costs. The purpose of this paper is to present and validate a mathematical model that managed care organizations can apply to administrative claims data to help locate members at risk for osteoporotic fracture and estimate future fracture rates. Using known risk factors from previous clinical studies, 92,000 members of a large Midwest health plan were placed in 1 of 4 risk categories based on historical claims markers: demographic/lifestyle (age, sex, smoking, alcoholism); steroid use; medical history (previous osteoporotic fracture, ordinary bone fracture, osteoporosis diagnosis, bone mineral density test); or steroid use with medical history. Logistic regression was used to assign a probability of fracture for the 4 groups over the next 2 years. These predictions were compared with actual fracture rates, and refined models were produced. The models were then validated by applying them to c...

Contributions to nephrology, 1984

Nephron, 1983

Serum cholesterol, triglycerides and their fractions in high density (HDL), low density (LDL) and... more Serum cholesterol, triglycerides and their fractions in high density (HDL), low density (LDL) and very low density (VLDL) lipoproteins were measured sequentially in fasting patients on continuous ambulatory peritoneal dialysis (CAPD) who entered a prospective study. Of the 30 who entered, all have been followed to 3 months, 24 to 6 months and decreasing numbers to 18 months. Serum total cholesterol, VLDL cholesterol, total triglycerides and VLDL triglycerides all rose significantly during the first 6 months and VLDL cholesterol has remained elevated to 18 months. Changes in other fractions have been insignificant or inconsistent. 1 patient has developed angina. No associations were found between use of high dextrose fluid, weight gain and hyperlipidemia, probably because of consistent practice between patients. Our results confirm the adverse effect of CAPD on serum lipids and the need for dietary modification but are broadly similar to the changes that have been observed during regular hemodialysis.

Drugs of the Future, 2008

Clinical Endocrinology, 1985

Prolactin secretion and biological activity have been investigated in 20 females with persistent ... more Prolactin secretion and biological activity have been investigated in 20 females with persistent idiopathic galactorrhoea who had normal resting serum prolactin levels at presentation. Results were compared with those in 34 normal controls. Hyperprolactinaemia, which was persistent in one and intermittent in the other, developed in two patients over an observation period of 1.5 to 8.5 years. Resting prolactin levels stayed normal in the remaining eighteen who were further investigated. Menstruation was disordered in only six of the 18, while ovulation occurred (serum progesterone > 20 nmol/l) in all seven patients who were studied over a 5 week period. Serum prolactin concentrations over 24 h were similar in patients and controls (24 h mean _+ SEM prolactin, 288 F 36 mU/I, patients, n= 7 ; 291 f 2 1 mU/l, controls, n=9) as were prolactin levels estimated twice weekly for 5 weeks. Prolactin responses to thyrotrophin-releasing hormone, 200 p g (at 20 min, 2417 f 658 mU/I, patients, n = 7; 21 13 f424 mU/1, controls, n = 8), the dopamine antagonist, domperidone, 10 mg (at 30 min, 5949 f 536 mU/l, patients, n = 7; 5858 4 460 mU/I, controls, n = 8) and

Clinical Endocrinology, 1985

Studies on intact animals and isolated rat hepatocytes have shown that arginine vasopression (AVP... more Studies on intact animals and isolated rat hepatocytes have shown that arginine vasopression (AVP) stimulates glycogen phosphorylase to break down glycogen and raise plasma glucose concentrations. Since no similar work has been performed on healthy human adults, the effect of moderate (25 pmol/min) and high (75 pmol/min) dose AVP infusion on plasma glucose, intermediary metabolites, glucose kinetics, and circulating glucagon and insulin concentrations was investigated. After AVP infusion, plasma glucose rose from 4.9 +/- 0.1 to a peak of 5.7 +/- 0.2 mmol/l (P less than 0.001), but no changes in blood lactate, pyruvate, alanine, glycerol or 3-hydroxybutyrate concentrations were observed. The glucose rise was accounted for entirely by an increase in the rate of appearance of glucose from 11.19 +/- 0.43 to 13.38 +/- 0.63 mu mol/kg/min (P less than 0.001). Infusion of AVP also increased plasma glucagon concentrations from 38 +/- 8 to 79 +/- 20 pg/l (P less than 0.01). The hyperglycaemic effect of AVP may be mediated solely by stimulation of glucagon release, but we cannot exclude direct stimulation of glycogen phosphorylase activity.

BMJ, 1985

... 4 Eriksson G, Eklund AE, Liden S, Zetterquist S. Comparison of different treat-ments of leg u... more ... 4 Eriksson G, Eklund AE, Liden S, Zetterquist S. Comparison of different treat-ments of leg ulcers: a controlled study using ... senior tutor and senior registrar Correspondence to: Dr BJ Collins, Department of Medicine, Institute of Clinical Science, Royal Victoria Hospital, Belfast ...

Medical engineering & physics, 1998

The stress levels in the femoral component of a total hip prosthesis (Corin Taper Fit, Corin Medi... more The stress levels in the femoral component of a total hip prosthesis (Corin Taper Fit, Corin Medical Ltd, Cirencester, Gloucestershire, UK) were calculated by finite element (FE) analysis. This prosthesis has two holes drilled in the shoulder to engage a stem introducer. There were no unacceptable stress levels around these holes. Instead the maximum stresses were around the periphery of the shaft of the stem, as has been observed for FE analyses of conventional designs. Three prostheses were also subjected to cyclic mechanical testing (peak load 2.3 kN) according to the appropriate British Standard. The holes were examined for cracks, before and after testing, by stereomicroscopy. All three specimens were able to withstand 5 million loading cycles with no evidence of damage. Thus it is possible to design a femoral component with holes in the shoulder, to accommodate a stem introducer, without creating unacceptable stress concentrations.

British journal of haematology, 1995

In these studies, platelet ageing during in vitro at 22 degrees C was compared with in vivo agein... more In these studies, platelet ageing during in vitro at 22 degrees C was compared with in vivo ageing using isotope labelling. Paired fresh and 5-d-stored platelets had a mean residual life-span (MRL) of 4.8 +/- 0.7 d and 3.2 +/- 0.9 d, respectively. After 2.1 +/- 0.4 d in vivo circulation, the MRL of the fresh platelets was equivalent to that of the 5-d-stored in vitro platelets. This suggests that platelet ageing for 5 d in vitro at 22 degrees C corresponds to 2.1 d in vivo ageing at 37 degrees C. Thus, the relative ageing at 22 degrees C in vitro was (2.1 d/5 d) = 0.42 of that at 37 degrees C in vivo. A similar ageing ratio (0.44) was obtained by measurement of the decrease in MRL during storage at 22 degrees C of platelets stored for 1, 5, 7, 10 and 14 d relative to the decrease in MRL of fresh platelets in vivo. ATP turnover rate at 22 degrees C was compared to the rate of 37 degrees C by measurement of the rates of platelet oxygen consumption and lactate production in vitro. In v...

Clinical science (London, England : 1979), 1984

The use of glycerol as an osmotic agent in two different concentrations (92 mmol/l and 272 mmol/l... more The use of glycerol as an osmotic agent in two different concentrations (92 mmol/l and 272 mmol/l) in peritoneal dialysis fluid was investigated over 3 days in six patients on continuous ambulatory peritoneal dialysis and compared with two concentrations of glucose (76 mmol/l and 215 mmol/l) in the same patients. The calorific value of the absorbed osmotic agent was lower, by 19% with isotonic and 22% with hypertonic solutions, when glycerol was used in place of glucose. However, glycerol provided significantly lower total ultrafiltration than glucose at each concentration, despite a higher initial osmotic pressure of the glycerol-based solutions. Thus, the higher concentration of glycerol required to provide equal ultrafiltration may offset any calorific advantage. Equilibration of creatinine and urea was slower and creatinine clearance lower with glycerol. Solutions containing glycerol were initially less acid (pH 6.5) than those containing glucose (pH 5.1). Blood glycerol levels,...

Lecture Notes in Computer Science, 1998

The paper focuses on practical analyses for logic programs with delay. The method described is fo... more The paper focuses on practical analyses for logic programs with delay. The method described is for downward-closed program properties and, in particular, groundness. A program transformation is defined which eliminates the delay statements but still enables an accurate approximation of the behaviour of delayed goals to be traced by the analyser. A simple prototype implementation has been built applying some of these methods to our analysis, and at this initial stage has achieved accurate results in promising times.

The proposal that dietary docosahexaenoic acid (DHA) enhances neurocognitive functioning in term ... more The proposal that dietary docosahexaenoic acid (DHA) enhances neurocognitive functioning in term infants is controversial. Theoretical evidence, laboratory research and human epidemiological studies have convincingly demonstrated that DHA deficiency can negatively impact neurocognitive development. However, the results from randomized controlled trials (RCTs) of DHA supplementation in human term-born infants have been inconsistent. This article will (i) discuss the role of DHA in the human diet, (ii) explore the physiological mechanisms by which DHA plausibly influences neurocognitive capacity, and (iii) seek to characterize the optimal intake of DHA during infancy for neurocognitive functioning, based on existing research that has been undertaken in developed countries (specifically, within Australia). The major observational studies and RCTs that have examined dietary DHA in human infants and animals are presented, and we consider suggestions that DHA requirements vary across individuals according to genetic profile. It is important that the current evidence concerning DHA supplementation is carefully evaluated so that appropriate recommendations can be made and future directions of research can be strategically planned.

PURPOSE: Impaired GABAergic inhibition has been implicated in the pathophysiology of epilepsy. Th... more PURPOSE:
Impaired GABAergic inhibition has been implicated in the pathophysiology of epilepsy. The possibility of a paradoxical excitatory effect of GABA in epilepsy has been suggested, but has not been investigated in vivo. We investigated pre- and post-synaptic GABAergic mechanisms in patients with idiopathic generalised epilepsy (IGE).
METHOD:
In 10 patients and 12 control subjects we explored short- and long-interval intracortical inhibition (SICI, LICI; post-synaptic GABAA and GABAB-mediated respectively) and long-interval intracortical facilitation (LICF; pre-synaptic disinhibition) using transcranial magnetic stimulation.

RESULTS:
While post-synaptic GABAB-mediated inhibition was unchanged in IGE (p=0.09), LICF was reduced compared to controls (controls: 141±17% of baseline; untreated patients: 107±12%, p=0.2; treated patients: 79±10%, p=0.003). GABAA-mediated inhibition was reduced in untreated patients (response amplitude 56±4% of baseline vs. 26±6% in controls, p=0.004) and normalised with treatment (37±12%, p=0.5 vs. controls). When measured during LICI, GABAA-mediated inhibition became excitatory in untreated IGE (response amplitude 120±10% of baseline, p=0.017), but not in treated patients.

CONCLUSION:
Pre- and post-synaptic GABA-mediated inhibitory mechanisms are altered in IGE. The findings lend in vivo support to evidence from experimental models and in vitro studies of human epileptic brain tissue that GABA may have a paradoxical excitatory role in ictogenesis.

Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Clinical science (London, England : 1979), 1989

1. A three-step hyperinsulinaemic euglycaemic clamp was performed in six uraemic patients before ... more 1. A three-step hyperinsulinaemic euglycaemic clamp was performed in six uraemic patients before dialysis and after 3 months of treatment with continuous ambulatory peritoneal dialysis, and in seven matched normal control subjects. Glucose turnover was assessed basally and during the clamp using [3-3H]glucose as a tracer. 2. The glucose infusion rate required to maintain euglycaemia was insignificantly higher in normal subjects compared with undialysed uraemic subjects at each insulin infusion rate. 3. The isotopically assessed total glucose turnover was also similar in normal and uraemic subjects. Basal hepatic glucose output was again similar in uraemic and control subjects and output was suppressed to a similar degree at each insulin infusion rate. 4. After treatment with continuous ambulatory peritoneal dialysis, the glucose infusion rate and the total glucose turnover during the clamp rose significantly at all three insulin concentrations (P less than 0.05), but remained insign...

Clinical therapeutics, 2001

Osteoporotic fractures are associated with significant morbidity, mortality, and health care cost... more Osteoporotic fractures are associated with significant morbidity, mortality, and health care costs. The purpose of this paper is to present and validate a mathematical model that managed care organizations can apply to administrative claims data to help locate members at risk for osteoporotic fracture and estimate future fracture rates. Using known risk factors from previous clinical studies, 92,000 members of a large Midwest health plan were placed in 1 of 4 risk categories based on historical claims markers: demographic/lifestyle (age, sex, smoking, alcoholism); steroid use; medical history (previous osteoporotic fracture, ordinary bone fracture, osteoporosis diagnosis, bone mineral density test); or steroid use with medical history. Logistic regression was used to assign a probability of fracture for the 4 groups over the next 2 years. These predictions were compared with actual fracture rates, and refined models were produced. The models were then validated by applying them to c...

Contributions to nephrology, 1984

Nephron, 1983

Serum cholesterol, triglycerides and their fractions in high density (HDL), low density (LDL) and... more Serum cholesterol, triglycerides and their fractions in high density (HDL), low density (LDL) and very low density (VLDL) lipoproteins were measured sequentially in fasting patients on continuous ambulatory peritoneal dialysis (CAPD) who entered a prospective study. Of the 30 who entered, all have been followed to 3 months, 24 to 6 months and decreasing numbers to 18 months. Serum total cholesterol, VLDL cholesterol, total triglycerides and VLDL triglycerides all rose significantly during the first 6 months and VLDL cholesterol has remained elevated to 18 months. Changes in other fractions have been insignificant or inconsistent. 1 patient has developed angina. No associations were found between use of high dextrose fluid, weight gain and hyperlipidemia, probably because of consistent practice between patients. Our results confirm the adverse effect of CAPD on serum lipids and the need for dietary modification but are broadly similar to the changes that have been observed during regular hemodialysis.

Drugs of the Future, 2008

Clinical Endocrinology, 1985

Prolactin secretion and biological activity have been investigated in 20 females with persistent ... more Prolactin secretion and biological activity have been investigated in 20 females with persistent idiopathic galactorrhoea who had normal resting serum prolactin levels at presentation. Results were compared with those in 34 normal controls. Hyperprolactinaemia, which was persistent in one and intermittent in the other, developed in two patients over an observation period of 1.5 to 8.5 years. Resting prolactin levels stayed normal in the remaining eighteen who were further investigated. Menstruation was disordered in only six of the 18, while ovulation occurred (serum progesterone > 20 nmol/l) in all seven patients who were studied over a 5 week period. Serum prolactin concentrations over 24 h were similar in patients and controls (24 h mean _+ SEM prolactin, 288 F 36 mU/I, patients, n= 7 ; 291 f 2 1 mU/l, controls, n=9) as were prolactin levels estimated twice weekly for 5 weeks. Prolactin responses to thyrotrophin-releasing hormone, 200 p g (at 20 min, 2417 f 658 mU/I, patients, n = 7; 21 13 f424 mU/1, controls, n = 8), the dopamine antagonist, domperidone, 10 mg (at 30 min, 5949 f 536 mU/l, patients, n = 7; 5858 4 460 mU/I, controls, n = 8) and

Clinical Endocrinology, 1985

Studies on intact animals and isolated rat hepatocytes have shown that arginine vasopression (AVP... more Studies on intact animals and isolated rat hepatocytes have shown that arginine vasopression (AVP) stimulates glycogen phosphorylase to break down glycogen and raise plasma glucose concentrations. Since no similar work has been performed on healthy human adults, the effect of moderate (25 pmol/min) and high (75 pmol/min) dose AVP infusion on plasma glucose, intermediary metabolites, glucose kinetics, and circulating glucagon and insulin concentrations was investigated. After AVP infusion, plasma glucose rose from 4.9 +/- 0.1 to a peak of 5.7 +/- 0.2 mmol/l (P less than 0.001), but no changes in blood lactate, pyruvate, alanine, glycerol or 3-hydroxybutyrate concentrations were observed. The glucose rise was accounted for entirely by an increase in the rate of appearance of glucose from 11.19 +/- 0.43 to 13.38 +/- 0.63 mu mol/kg/min (P less than 0.001). Infusion of AVP also increased plasma glucagon concentrations from 38 +/- 8 to 79 +/- 20 pg/l (P less than 0.01). The hyperglycaemic effect of AVP may be mediated solely by stimulation of glucagon release, but we cannot exclude direct stimulation of glycogen phosphorylase activity.

BMJ, 1985

... 4 Eriksson G, Eklund AE, Liden S, Zetterquist S. Comparison of different treat-ments of leg u... more ... 4 Eriksson G, Eklund AE, Liden S, Zetterquist S. Comparison of different treat-ments of leg ulcers: a controlled study using ... senior tutor and senior registrar Correspondence to: Dr BJ Collins, Department of Medicine, Institute of Clinical Science, Royal Victoria Hospital, Belfast ...

Medical engineering & physics, 1998

The stress levels in the femoral component of a total hip prosthesis (Corin Taper Fit, Corin Medi... more The stress levels in the femoral component of a total hip prosthesis (Corin Taper Fit, Corin Medical Ltd, Cirencester, Gloucestershire, UK) were calculated by finite element (FE) analysis. This prosthesis has two holes drilled in the shoulder to engage a stem introducer. There were no unacceptable stress levels around these holes. Instead the maximum stresses were around the periphery of the shaft of the stem, as has been observed for FE analyses of conventional designs. Three prostheses were also subjected to cyclic mechanical testing (peak load 2.3 kN) according to the appropriate British Standard. The holes were examined for cracks, before and after testing, by stereomicroscopy. All three specimens were able to withstand 5 million loading cycles with no evidence of damage. Thus it is possible to design a femoral component with holes in the shoulder, to accommodate a stem introducer, without creating unacceptable stress concentrations.

British journal of haematology, 1995

In these studies, platelet ageing during in vitro at 22 degrees C was compared with in vivo agein... more In these studies, platelet ageing during in vitro at 22 degrees C was compared with in vivo ageing using isotope labelling. Paired fresh and 5-d-stored platelets had a mean residual life-span (MRL) of 4.8 +/- 0.7 d and 3.2 +/- 0.9 d, respectively. After 2.1 +/- 0.4 d in vivo circulation, the MRL of the fresh platelets was equivalent to that of the 5-d-stored in vitro platelets. This suggests that platelet ageing for 5 d in vitro at 22 degrees C corresponds to 2.1 d in vivo ageing at 37 degrees C. Thus, the relative ageing at 22 degrees C in vitro was (2.1 d/5 d) = 0.42 of that at 37 degrees C in vivo. A similar ageing ratio (0.44) was obtained by measurement of the decrease in MRL during storage at 22 degrees C of platelets stored for 1, 5, 7, 10 and 14 d relative to the decrease in MRL of fresh platelets in vivo. ATP turnover rate at 22 degrees C was compared to the rate of 37 degrees C by measurement of the rates of platelet oxygen consumption and lactate production in vitro. In v...

Clinical science (London, England : 1979), 1984

The use of glycerol as an osmotic agent in two different concentrations (92 mmol/l and 272 mmol/l... more The use of glycerol as an osmotic agent in two different concentrations (92 mmol/l and 272 mmol/l) in peritoneal dialysis fluid was investigated over 3 days in six patients on continuous ambulatory peritoneal dialysis and compared with two concentrations of glucose (76 mmol/l and 215 mmol/l) in the same patients. The calorific value of the absorbed osmotic agent was lower, by 19% with isotonic and 22% with hypertonic solutions, when glycerol was used in place of glucose. However, glycerol provided significantly lower total ultrafiltration than glucose at each concentration, despite a higher initial osmotic pressure of the glycerol-based solutions. Thus, the higher concentration of glycerol required to provide equal ultrafiltration may offset any calorific advantage. Equilibration of creatinine and urea was slower and creatinine clearance lower with glycerol. Solutions containing glycerol were initially less acid (pH 6.5) than those containing glucose (pH 5.1). Blood glycerol levels,...

Lecture Notes in Computer Science, 1998

The paper focuses on practical analyses for logic programs with delay. The method described is fo... more The paper focuses on practical analyses for logic programs with delay. The method described is for downward-closed program properties and, in particular, groundness. A program transformation is defined which eliminates the delay statements but still enables an accurate approximation of the behaviour of delayed goals to be traced by the analyser. A simple prototype implementation has been built applying some of these methods to our analysis, and at this initial stage has achieved accurate results in promising times.