Optimising Islet Transplantation With Vascularized Tissue Engineering Chambers
Funder
National Health and Medical Research Council
Funding Amount
$451,651.00
Summary
Diabetics have high blood sugar levels because cells in the pancreas known as islets produce too little of the hormone insulin. Most diabetics need daily insulin injections to maintain normal blood sugar levels. Transplanting islets is the most promising way to treat type 1 diabetes, but, apart from the obvious difficulty of rejection of foreign islets, several major problems remain: (1) there are insufficient pancreata (and therefore islets) for transplantation; and (2) the efficiency of delive ....Diabetics have high blood sugar levels because cells in the pancreas known as islets produce too little of the hormone insulin. Most diabetics need daily insulin injections to maintain normal blood sugar levels. Transplanting islets is the most promising way to treat type 1 diabetes, but, apart from the obvious difficulty of rejection of foreign islets, several major problems remain: (1) there are insufficient pancreata (and therefore islets) for transplantation; and (2) the efficiency of delivery of surviving islet transplants is too low. In pilot studies we have grown a new living pancreatic organ in mice by inserting islets from genetically-related mice together with a structural protein matrix, growth factors and blood vessels inside a plastic chamber. The blood vessels maintain nutrition to the islet cells and simultaneously allow insulin to be released into the bloodstream, thus normalising the high blood sugar in diabetics. In Aim 1 of these experiments we will find the optimal way to grow mature islets in blood vessel-containing chambers in diabetic mice, focusing on (a) the best time to add islets to the chamber - 0, 1 or 2 weeks after establishment, (b) the minimum number of islets to effectively normalise blood sugar and (c) how long we can keep islets alive and functional in chambers, examining periods up to 12 months. In Aim 2 we will test the ability of islet stem cells (provided by our co-investigators at Walter and Eliza Hall Institute, Melbourne) to survive in the chambers and to produce sufficient insulin to effectively lower blood sugar levels to normal in diabetic mice. In Aim 3 we will grow human islets in chambers in special diabetic mice that do not reject foreign tissue, in order to confirm similar behaviour of human islets in this controlled environment. Using this data, we hope to create a research model of functioning islets, that is accessible, retrievable and manipulable, for the further study of diabetes and transplantation.Read moreRead less
Outcomes Of The Arterial Switch Operation: A Multi-centre Study
Funder
National Health and Medical Research Council
Funding Amount
$86,733.00
Summary
The arterial switch operation is the surgery of choice for children born with transposition of the great arteries, a congenital heart defect where the main two vessels of the heart arise from wrong pumping chambers of the heart. There are very few studies looking at adults after this operation. We aim to study all patients who have had an arterial switch. The results of this study will further increase our knowledge of the long term consequences of having the arterial switch operation.
Vascular Targeting Combined With Radiosurgery In An Arteriovenous Malformation Rat Model
Funder
National Health and Medical Research Council
Funding Amount
$102,345.00
Summary
Cerebral arteriovenous malformations are an important cause of stroke and brain bleeds. In many patients such a stroke can result in severe disability or death. Current management involves a combination of surgery, radiation therapy and endovascular treatments and carry a high risk of complications. This research project suggests a new form of treatment whereby irradiating the vascular malformation a medication could be administered to cause targeted clotting of the malformation.
The Role Of Tissue Factor Pathway Inhibitor (TFPI) In The Pathogenesis Of Lymphatic Malformations
Funder
National Health and Medical Research Council
Funding Amount
$87,198.00
Summary
Lymphatic malformations or cystic hygomas are growths of abnormal blood vessels called 'lymphatic vessels'. They are present at birth, commonly affect the head and neck, and can cause lifelong problems due to growth in size and frequent infections. Surgical treatment does not offer a cure, and problems often persist lifelong. The finding that blood clots are continuously forming and breaking down in these growths may provide a clue to relieving symptoms and understanding the cause of this condit ....Lymphatic malformations or cystic hygomas are growths of abnormal blood vessels called 'lymphatic vessels'. They are present at birth, commonly affect the head and neck, and can cause lifelong problems due to growth in size and frequent infections. Surgical treatment does not offer a cure, and problems often persist lifelong. The finding that blood clots are continuously forming and breaking down in these growths may provide a clue to relieving symptoms and understanding the cause of this condition.Read moreRead less
Randomised Controlled Trials Of Laparoscopic Techniques For Antireflux Surgery
Funder
National Health and Medical Research Council
Funding Amount
$1,031,381.00
Summary
Gastro-oesophageal reflux is common, with approximately 10% of Australians now using medication to control symptoms. Many Australians will need this medication for life, unless they undergo surgery. The cost of treating reflux is growing. Since 1992 the annual growth rate of the Pharmaceutical Benefits Scheme expenditure on reflux medication has been 13%, and the annual cost for the treatment of reflux now exceeds $1 billion. Not all patients with reflux are satisfied with medication, as some co ....Gastro-oesophageal reflux is common, with approximately 10% of Australians now using medication to control symptoms. Many Australians will need this medication for life, unless they undergo surgery. The cost of treating reflux is growing. Since 1992 the annual growth rate of the Pharmaceutical Benefits Scheme expenditure on reflux medication has been 13%, and the annual cost for the treatment of reflux now exceeds $1 billion. Not all patients with reflux are satisfied with medication, as some continue to experience symptoms. Surgery is the only treatment which will cure reflux. It has a clear role in the treatment of patients with ongoing symptoms, those who don t want to take tablets, and patients with a large hiatus hernia in whom symptoms occur due to the relocation of the stomach from the abdomen into the chest. Approximately 5,000 Australians per year undergo surgery for reflux. The standard operation achieves a good outcome in approximately 90%, although some patients are troubled by side effects. To reduce the risk of this, the original procedure has been modified. However, the evidence supporting modifications has until recently been limited. The best way to compare different operations is in randomised trials. The majority of the largest and best trials addressing this area have been undertaken in Adelaide. We have already entered 504 patients into 5 randomised trials, 4 conducted entirely in Adelaide, and one across multiple sites with the cooperation of 15 Australasian surgeons. These trials have provided a more reliable evidence base for surgeons undertaking surgery for reflux. However, long term follow-up is required to ensure that conclusions drawn are valid at late follow-up. In addition we are establishing 2 new randomised trials, which will determine how best to perform surgery for reflux, and how best to repair a large hiatus hernia. These studies will be undertaken in collaboration with more than 25 other surgeons throughout Australia.Read moreRead less
Multidisciplinary Management Of Vertebral Metastases Identification Of Standardized Surgical Guidelines
Funder
National Health and Medical Research Council
Funding Amount
$358,604.00
Summary
The spine is the commonest site of cancer spread to the skeleton and often leads to severe pain and paralysis. Recent advances in surgical techniques enable removal and reconstruction of all tumours of the spine. However, surgery remains controversial because of the need to weigh up the patient’s estimated length of survival with the risks of surgery. Our aims are to develop clear guidelines on which patients to perform surgery on, and what type of surgery to perform.
Three Dimensional Ex Vivo Modelling Of Neuromuscular Junction Formation
Funder
National Health and Medical Research Council
Funding Amount
$120,253.00
Summary
Re-establishing functional connections between neurons and muscle is an important step in the recovery process after neuromuscular injury or surgery. In order to study the connection forming process in isolation a biological model of nerve muscle connection formation is required. This study aims to buid a biological model consisting of neurons and muscles in a three dimensional environment and to assess the quality of the functional connections that develop.
Perioperative Beta-blockade To Prevent Cardiac Morbidity In High-risk Patients Undergoing Surgery (The POISE Study)
Funder
National Health and Medical Research Council
Funding Amount
$189,625.00
Summary
Non-cardiac surgery is associated with significant risk of complications and death, particularly in elderly patients who are known to have heart disease, or who have risk factors for it (ie smoking, high blood pressure). About 11% of the Australian population are currently taking medications for heart disease or high blood pressure and about 80% have at least one risk factor for heart disease. As more than 2 million Australians have general anaesthesia for non-cardiac surgery every year, a subst ....Non-cardiac surgery is associated with significant risk of complications and death, particularly in elderly patients who are known to have heart disease, or who have risk factors for it (ie smoking, high blood pressure). About 11% of the Australian population are currently taking medications for heart disease or high blood pressure and about 80% have at least one risk factor for heart disease. As more than 2 million Australians have general anaesthesia for non-cardiac surgery every year, a substantial group of patients are therefore at risk of an adverse outcome following surgery. Despite the magnitude of this problem, however, few studies have established treatments to decrease the risk of complications and death following surgery. Beta-blockers are a group of drugs which have been used for decades in the treatment of heart disease and high blood pressure. Beta-blockers are known to improve the way the heart copes with the stress of surgery. They decrease the heart rate, make the heart more efficient at using energy and reduce the likelihood of imbalance between oxygen supply and demand. Some previous studies showed that beta-blockers may reduce the risk of heart attack and death for up to 2 years after surgery. However, other studies have shown no effect of beta-blockers on outcome. These previous studies have involved small numbers of patients who may not represent the broader population having surgery. We therefore propose to undertake a large trial to definitively answer the question about whether beta-blockers improve the outcome after non-cardiac surgery in patients with, or at risk of, heart disease. Even if the effect of beta-blockers is relatively modest, because such large numbers of patients with heart disease have surgery, the overall effect on the rate of complications and death in the population could be very significant. The results of this study could have major implications for the success of, and cost of, surgery worldwide.Read moreRead less