Susceptibility To Venous Leg Ulceration: Investigation Of The First Genetic Risk Factor
Funder
National Health and Medical Research Council
Funding Amount
$291,000.00
Summary
This application aims to confirm our preliminary identification of the first candidate gene as a risk factor for developing venous leg ulceration. Since patients with venous leg ulcers experience pain and psychological consequences including anger and depression, all of which impact negatively on quality of life, active prevention of ulceration will have significant lifestyle and financial benefits. Venous leg ulcers occur in patients who have venous disease, in particular in patients with previ ....This application aims to confirm our preliminary identification of the first candidate gene as a risk factor for developing venous leg ulceration. Since patients with venous leg ulcers experience pain and psychological consequences including anger and depression, all of which impact negatively on quality of life, active prevention of ulceration will have significant lifestyle and financial benefits. Venous leg ulcers occur in patients who have venous disease, in particular in patients with previous deep vein thrombosis. However, not all patients with a deep vein thrombosis or other forms of venous disease will go on to develop a venous ulcer. Our preliminary results show that patients with a venous ulcer have a greater frequency of this gene than healthy controls without venous ulcers, and suggest that patients with the candidate gene have a greater risk of developing venous ulceration. In this study we aim to determine whether the gene itself contributes to ulcer susceptibility or whether it is just a marker of that susceptibility. We can do this by assessing related genes and the levels of the protein produced by this gene. In this study we also aim to assess whether patients with a proven deep vein thrombosis are more likely to develop venous ulceration if they have the candidate gene. These studies have the potential to lead to the development of a diagnostic screening test for use in patients with venous disease, to assess the likelihood of developing leg ulceration. This will enable more active treatment to prevent leg ulceration. If this gene contributes to ulcer susceptibility new specific treatments may be developed for ulcer management and prevention.Read moreRead less
Heritability And Biological Consequences Of Human Variation In Mitotic Recombination
Funder
National Health and Medical Research Council
Funding Amount
$130,906.00
Summary
Cells in our bodies constantly sustain damage to their genetic material (genes) most of which is efficiently repaired. Some is not and accumulated damage to genes in a cell can start a cancer. There are several repair mechanisms that cells possess which have evolved since the earliest life-forms. One repair mechanism homologous recombination repair will, as a minor by-product of its activity, produce an event called mitotic recombination (MR). MR causes a loss of diversity of genes and this can ....Cells in our bodies constantly sustain damage to their genetic material (genes) most of which is efficiently repaired. Some is not and accumulated damage to genes in a cell can start a cancer. There are several repair mechanisms that cells possess which have evolved since the earliest life-forms. One repair mechanism homologous recombination repair will, as a minor by-product of its activity, produce an event called mitotic recombination (MR). MR causes a loss of diversity of genes and this can contribute to cancer rather than prevent it. We have shown that the rate at which MR occurs varies very widely in humans. In this project we will devise a simple method for measuring MR, use identical and non identical twins to find if the rate of MR is inherited and finally see whether the rate of MR is associated with risk of cancer, as we expect.Read moreRead less
PREOPERATIVE RISK FACTORS, ADVERSE OUTCOMES AND EFFECTS OF EPIDURAL AND SPINAL ANAESTHESIA
Funder
National Health and Medical Research Council
Funding Amount
$66,110.00
Summary
Anaesthesia and major surgery in patients with coexisting important medical problems present a major challenge to health professionals to avoid and minimise life threatening complications of such surgery. Accurate prediction of which patients are likely to fare badly, and therefore need more intensive peri-operative care and supervision, and knowing definitively whether epidural techniques really do improve the outcome of surgery are issues of central importance in the practice of anaesthesia. P ....Anaesthesia and major surgery in patients with coexisting important medical problems present a major challenge to health professionals to avoid and minimise life threatening complications of such surgery. Accurate prediction of which patients are likely to fare badly, and therefore need more intensive peri-operative care and supervision, and knowing definitively whether epidural techniques really do improve the outcome of surgery are issues of central importance in the practice of anaesthesia. Providing clear answers to both questions requires careful analysis of large amounts of data in which systematic and random errors have been minimised. Databases from well-designed and supervised clinical trials represent an invaluable resource in this regard because they have been compiled through the rigorous application of unambiguous definitions and protocols during the process of recording, coding and entering the information. By bringing together the resources and expertise of the MASTER Trial group and the Collaborative Overview of Randomised of Trials of Regional Anaesthesia (CORTRA), both of which are major international projects led from the Australasian region, we have a unique opportunity to provide exceptionally robust answers to some of the most challenging issues in anaesthesia. The combined study of two large international databases will provide a more precise quantitative analysis of the components of preoperative risk and their relationship to life threatening post operative complications, and the possible role of epidural and spinal anaesthesia in minimising risk by reducing the frequency of these complications.Read moreRead less
Predicting The Individual Risk Of Prostate Cancer In Australian Men
Funder
National Health and Medical Research Council
Funding Amount
$348,656.00
Summary
Prostate cancer is a major cause of disability and death in Australian men. A number of factors, particularly age and family history, influence the risk of prostate cancer but, in contrast to breast cancer, we don't know what is the risk of developing prostate cancer over a period of time for a man with a specific set of risk factors. In fact, while a number of statistical models have been developed that use a woman's risk factor profile to estimate her risk of breast cancer, none is currently a ....Prostate cancer is a major cause of disability and death in Australian men. A number of factors, particularly age and family history, influence the risk of prostate cancer but, in contrast to breast cancer, we don't know what is the risk of developing prostate cancer over a period of time for a man with a specific set of risk factors. In fact, while a number of statistical models have been developed that use a woman's risk factor profile to estimate her risk of breast cancer, none is currently available for prostate cancer. We will apply standard statistical methods to existing data from the Australian Risk Factors for Prostate Cancer study and from the Australian Institute of Health and Welfare to develop a prostate cancer risk prediction model. We will test how factor like age, detailed family history, diet, baldness status and possibly previous PSA tests and prostate biopsies predict the risk. After developing the model, we will test the accuracy of the predictions in three ways. First, using existing data from the Australian Prostate Cancer Family Study, we will see whether the number of cases in a group of men is close to the number predicted by the model (calibration). Second, to test whether the model discriminate well men who develop prostate cancer from those who do not, we will collect family trees in a sample from the Melbourne Collaborative Cohort Study. We will use these data also to estimate the optimal cut point: men above this level of risk will be considered at high risk. Third, we will apply the model to existing data from the Dutch Prostate Cancer Family Study (DPCFS) to test whether the optimal cut point identify high-risk men and to validate the model in a non-Australian population. Finally, we will prepare a computer package that health professionals will use as decision-making tool in different scenarios including individual cancer risk assessment, design of prevention trials and targeting prevention programs to high-risk men.Read moreRead less
SES And Injury In Children: A Cohort Study To Identify And Measure The Effects Of Preventable Mediating Factors
Funder
National Health and Medical Research Council
Funding Amount
$360,505.00
Summary
While changing an individual or group SES is at best a long term and challenging social objective, proximal risk factors for injury can be more readily modified. Once the proximal risk factor differential across SES groups has been adequately delineated, then the possibility arises for targeted public health intervention to redress the SES differential in the incidence of injury. The sophistication of the proposed modeling will result in a good assessment of the best point to target.
Factor V Leiden Mutation: A Contributory Factor For Cerebral Palsy?
Funder
National Health and Medical Research Council
Funding Amount
$72,595.00
Summary
Cerebral palsy is the commonest physical disability in childhood. It has a major impact on individuals and families. In a significant proportion of cases, the cause is unknown so further research is essential to define the reasons for this condition, and thereby develop preventative strategies. Two mutations have been identified that predispose carriers to develop blood clots (called thrombosis). These mutations are the Factor V Leiden mutation and the coagulation gene for prothrombin (also know ....Cerebral palsy is the commonest physical disability in childhood. It has a major impact on individuals and families. In a significant proportion of cases, the cause is unknown so further research is essential to define the reasons for this condition, and thereby develop preventative strategies. Two mutations have been identified that predispose carriers to develop blood clots (called thrombosis). These mutations are the Factor V Leiden mutation and the coagulation gene for prothrombin (also known as the G20210A mutation). If blood clots form in, or travel to the brain (embolism), they can obstruct the blood supply causing damage that may result in cerebral palsy in young children. Our research will investigate both mothers of children with cerebral palsy, and the children themselves. The study of the mothers will determine whether those that are carriers of these mutations are at an increased risk of having children with cerebral palsy. Factors that may precipitate the development of blood clots, such as smoking during pregnancy, will be investigated. The children with cerebral palsy will be studied to determine whether they carry the mutations, and if so, whether they have brain scan evidence of previous blood clots. Children will be tested for the mutation using the blood spot taken routinely early in life. These blood spots are stored on cards (Guthrie cards) and are available for research following parental consent. The mothers will be tested for the mutation by using a saliva sample and will also be interviewed to obtain details of their pregnancies. As a result of this project, useful information will be provided for families and health care providers. It will be established whether these mutations play a role in the genesis of cerebral palsy. In addition, data about possible factors which may increase the risk in carrier mothers, such as smoking, will be provided.Read moreRead less