It is known that about 10% of patients over the age of 55 have difficulty with cognition and thinking 3 months after surgery and anaesthesia. Over 2 million operations involving anaesthesia are administered in Australia every year and increasingly the patients are elderly and thus exposed to the risk of cognitive decline after surgery. We have preliminary data showing that people who have mild changes in cognitive function before the surgery (known as mild cognitive impairment) are susceptible t ....It is known that about 10% of patients over the age of 55 have difficulty with cognition and thinking 3 months after surgery and anaesthesia. Over 2 million operations involving anaesthesia are administered in Australia every year and increasingly the patients are elderly and thus exposed to the risk of cognitive decline after surgery. We have preliminary data showing that people who have mild changes in cognitive function before the surgery (known as mild cognitive impairment) are susceptible to further cognitive decline after anaesthesia and surgery. In order to explore the relationship between preoperative cognitive function and postoperative cognitive decline we plan to measure cognition in patients scheduled for elective hip replacement surgery. This is done by asking patients to complete a standard battery of cognitive tests. We will be then able to identify those patients who already have mild cognitive impairment before surgery and by repeated testing after the operation will be able to demonstrate if preoperative cognitive status is a determinant of postoperative cognitive dysfunction. The primary aim of the research is to test whether cognitive impairment before surgery leads to cognitive deficit after surgery in patients over the age of 65 undergoing total hip replacement surgery. The study will also establish the prevalence of pre-operative mild cognitive impairment and the magnitude of postoperative cognitive dysfunction after surgery in this patient group. The study will explore the relationship between preoperative cognitive status and postoperative cognitive deficit , providing information about the incidence, natural history and risk factors of postoperative cognitive deficit. This work will enable further research to isolate specific causative factors and identify therapeutic and prophylactic strategies.Read moreRead less
Clinical Feasibility Study Of Omega-3 PUFA Therapy For The Reduction Of Post-cardiac Surgery Atrial Arrhythmias
Funder
National Health and Medical Research Council
Funding Amount
$442,092.00
Summary
The aim of this study is to determine the molecular and clinical impact of omega-3 polyunsaturated fatty acids (PUFA) pre-treatment 2 weeks before cardiac surgery in 150 patients. The outcome of this proposal will indicate proof of molecular concepts, clinical feasibility and specific design elements of a future, large scale, placebo controlled, prospective randomised trial of oral therapy with omega-3 polyunsaturated fatty acids (PUFA). Recently, omega-3 PUFA via fish diet was reported to be li ....The aim of this study is to determine the molecular and clinical impact of omega-3 polyunsaturated fatty acids (PUFA) pre-treatment 2 weeks before cardiac surgery in 150 patients. The outcome of this proposal will indicate proof of molecular concepts, clinical feasibility and specific design elements of a future, large scale, placebo controlled, prospective randomised trial of oral therapy with omega-3 polyunsaturated fatty acids (PUFA). Recently, omega-3 PUFA via fish diet was reported to be linked to low incidence of AF. The main aim is to provide a cheap and safe preventative therapy against post-operative atrial fibrillation (AF), a key heart rhythm disorder that occurs in at least 1 in 4 patients after heart surgery and increases post-operative complications, limits recovery and increases hospital stay and cost. Biochemical study elements are important to gain valuable insight into the molecular mechanisms (directly in human heart) that underlie post-operative heart rhythm disorder and may delineate new more precise molecular targets for therapy. No previous clinical study has ever examined whether omega-3 PUFA therapy prevents post-operative heart rhythm disorder. Use of 3g-day omega-3 PUFA pre-treatment in the surgical setting has been shown to be safe in a number of small studies, including our own. Our preliminary data indicates that therapy increases heart and blood content of omega-3 PUFA ~2-fold, and reduces the incidence of AF. Post-operative AF is an expensive resource burden in all cardiothoracic surgery units of Australian hospitals and targets key health priorities. Due to the non-patentable nature of omega-3 PUFA, significant industry based support for clinical research is limited. A positive outcome would rapidly pave the way for widespread use in elective surgery. Reduced length of hospital stay, cost-savings, and the increase in productivity as healthy individuals return to their communities would nationally repay the investment many fold.Read moreRead less
Our lives depend upon maintaining the correct body temperature. Failure to regulate it properly may be lethal. This is particularly true in the elderly, who are more susceptible on the one hand to heat stroke and on the other to hypothermia. Many die each year from both these causes. Body temperature is regulated by the brain, yet our understanding of how and where in the brain this happens is poor. This proposal aims to work out the 'wiring diagram' of brain temperature control pathways in rats ....Our lives depend upon maintaining the correct body temperature. Failure to regulate it properly may be lethal. This is particularly true in the elderly, who are more susceptible on the one hand to heat stroke and on the other to hypothermia. Many die each year from both these causes. Body temperature is regulated by the brain, yet our understanding of how and where in the brain this happens is poor. This proposal aims to work out the 'wiring diagram' of brain temperature control pathways in rats and to begin to extend this knowledge to humans. This work will generate new knowledge about a vital function. The insights obtained will inform and guide future strategies in aged care, intensive care and perioperative care.Read moreRead less
My research focuses on the mechanisms responsible for diabetic kidney and heart complications with an emphasis on identifying novel targets as the basis for developing new treatment to reduce the burden of these complications. It is hypothesised that diabetic complications arise as a result of a number of key factors, the most important being chronic elevation of blood glucose.
The Relationship Between Non-Alcoholic Fatty Liver Disease And Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$133,351.00
Summary
Non alcoholic Fatty Liver Disease (NAFLD) threatens to become a major public health problem. Its increasing prevalence is associated with parallel increases in obesity and diabetes. This study aims to understand the mechanisms involved in progression to liver failure and liver cancer in the setting of diabetes and the impact of NAFLD on blood sugar levels and diabetes complications (esp. cardiovascular). Using a recently developed animal model of type 2 diabetes and fatty liver, it will better d ....Non alcoholic Fatty Liver Disease (NAFLD) threatens to become a major public health problem. Its increasing prevalence is associated with parallel increases in obesity and diabetes. This study aims to understand the mechanisms involved in progression to liver failure and liver cancer in the setting of diabetes and the impact of NAFLD on blood sugar levels and diabetes complications (esp. cardiovascular). Using a recently developed animal model of type 2 diabetes and fatty liver, it will better define a novel therapeutic agent.Read moreRead less
The Role Of Angiotensin Converting Enzyme 2 In Diabetic Complications
Funder
National Health and Medical Research Council
Funding Amount
$453,144.00
Summary
Most heart attacks and strokes arise from narrowing of the arteries. This process is regulated by a number of hormonal pathways. One of the most important is the renin angiotensin system. Our group has demonstrated important changes in this pathway which play a pivotal role in regulating the development of atherosclerosis and its response to treatment. It is predicted that these studies will provide critical information to develop innovative treatment strategies for cardiovascular disease.
RAGE And ACE2 Shedding As Therapeutic Targets In Diabetes And Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$748,447.00
Summary
We have previously demonstrated the pivotal role of two shed proteins, Receptor for Advanced Glycation End-products (RAGE) and Angiotensin Converting Enzyme Receptor 2 (ACE2) in heart disease and diabetic complications. In this project, we will use a novel technologies to modify shedding of these proteins from the cell surface and alter their ability to cause disease.
HYPE: Hypertension And Preeclampsia After Non-steroidal Use For Post-partum Pain Relief; A Prospective, Stratified, Randomised Placebo-controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$174,504.00
Summary
After caesarean delivery of a baby most women will require analgesia. Traditionally anti-inflammatory medications (eg.diclofenac) have been given. Evidence exists that this medicine may increase the mother�s blood pressure. This can result in a longer hospital stay, blood pressure medications and exposure to the risks of high blood pressure (eg.stroke and increased bleeding). This study examines the effect of diclofenac on the mother�s blood pressure, analgesia and investigates the mechanisms be ....After caesarean delivery of a baby most women will require analgesia. Traditionally anti-inflammatory medications (eg.diclofenac) have been given. Evidence exists that this medicine may increase the mother�s blood pressure. This can result in a longer hospital stay, blood pressure medications and exposure to the risks of high blood pressure (eg.stroke and increased bleeding). This study examines the effect of diclofenac on the mother�s blood pressure, analgesia and investigates the mechanisms behind the increased blood pressure.Read moreRead less
Role Of Placental Retroviral Protein Syncytin Carried On Exosomes In Mediating Vulnerability Of Pregnant Women To Influenza
Funder
National Health and Medical Research Council
Funding Amount
$645,145.00
Summary
50% of the women who died due to swine flu were pregnant. This project will examine if factors produced by the placenta make the pregnant woman more susceptible to influenza.