Alternatives To Homologous Blood Transfusion - Development Of Evidence- Based Decision Aids.
Funder
National Health and Medical Research Council
Funding Amount
$213,697.00
Summary
Transfusion of donor blood is the traditional means of treating blood loss resulting from injury or during surgery. Donor blood is in short supply and in the past there have been episodes of contamination by viruses that have led to hepatitis and AIDS. Consequently there is much interest in a range of techniques designed to reduce the need for transfusion of donor blood. One of the most popular is transfusion of patients' own blood (autologous transfusion). Despite the popularity of some of thes ....Transfusion of donor blood is the traditional means of treating blood loss resulting from injury or during surgery. Donor blood is in short supply and in the past there have been episodes of contamination by viruses that have led to hepatitis and AIDS. Consequently there is much interest in a range of techniques designed to reduce the need for transfusion of donor blood. One of the most popular is transfusion of patients' own blood (autologous transfusion). Despite the popularity of some of these techniques their true value is not really proven. They may be capable of diminishing the need for a transfusion of donor blood, but the long-term effects of this are not clear. In addition the preparation of autologous blood is a burden for overworked blood banks, and autologous blood may itself be associated with its own problems. The main aims of this study are to carry out reviews of the best quality trials of the various alternatives to transfusion of donor blood and to carry out surveys to find out what patients and doctors think. In a third phase of the project we will use the information gathered in the first two phases to design decision aids. These are comprehensive structured summaries of the available evidence to enable patients and their physicians to collaborate in making informed decisions that are likely to lead to the best outcomes for patients. The products of the research will be a number of reviews of 'best evidence' that appear in the International Cochrane Library, available to health professionals around the world. In addition, the decision aids, if successful, will be made available in a form that can be used by all Australian patients who are facing surgery that is likely to require a blood transfusion.Read moreRead less
Quantitative In Vitro-in Vivo Extrapolation: Realising The Promise
Funder
National Health and Medical Research Council
Funding Amount
$529,509.00
Summary
Most drugs are 'broken down', or metabolised, in the body by enzymes which are located mainly in liver. Knowing the efficiency of drug metabolism in patients is important for the discovery of new drugs and for the rational use of established drugs. This project will develop in vitro, or test-tube, approaches that predict how well a drug is metabolised in humans and whether it will interact with coadminsitered drugs. In turn, this allows prediction of drug dosage and frequency of administration.
THE NATURAL HISTORY OF COGNITIVE IMPAIRMENT AND DEMENTIA IN A STROKE COHORT
Funder
National Health and Medical Research Council
Funding Amount
$290,747.00
Summary
In a current NHMRC-funded study, we have examined 200 stroke patients (and 100 control subjects) at 3 months after a stroke and one year later, and identified those who have impairment in memory and other cognitive functions. We have also studied these subjects in detail from a psychiatric perspective and performed brain scans on them using magentic resonance imaging. We find that many stroke patients have problems with their cognitive functioning which has a major impact on their lives. A large ....In a current NHMRC-funded study, we have examined 200 stroke patients (and 100 control subjects) at 3 months after a stroke and one year later, and identified those who have impairment in memory and other cognitive functions. We have also studied these subjects in detail from a psychiatric perspective and performed brain scans on them using magentic resonance imaging. We find that many stroke patients have problems with their cognitive functioning which has a major impact on their lives. A large number also become depressed. These consequences of stroke are not given sufficient importance by clinicians. The fact that stroke is a common problem in the elderly, and our society is aging, makes this a problem of major public health significance. In the new proposal, we plan to study these subjects up to 3 years with repeat neuropsychiatric assessments and brain scans to investigate the natural history of stroke-related cognitive impairment. We will determine whether further new cases of dementia develop in the period 1-3 years, what happens to the brain lesions picked up on brain scans, and how these deficiencies affect the patients' living status and their longevity. We will be able to determine the factors that lead to a good outcome, and suggest strategies that may be applicable to improve the functioning of these individuals.Read moreRead less
Mechanisms Of Hypoglycaemic Damage In Developing Brain- A Protective Role For The Insulin-like Growth Factor System
Funder
National Health and Medical Research Council
Funding Amount
$408,055.00
Summary
The developing brain in the newborn infant or young child is vulnerable to many damaging influences. It is highly dependent on its essential fuel, glucose. Hypoglycemia, or lack of glucose availability, is therefore among the most damaging insults to the young brain, potentially leading to learning difficulties, developmental delay, cerebral palsy or epilepsy. Babies born premature or very small are at risk, as are those exposed to excessive insulin, such as infants of diabetic mothers. Children ....The developing brain in the newborn infant or young child is vulnerable to many damaging influences. It is highly dependent on its essential fuel, glucose. Hypoglycemia, or lack of glucose availability, is therefore among the most damaging insults to the young brain, potentially leading to learning difficulties, developmental delay, cerebral palsy or epilepsy. Babies born premature or very small are at risk, as are those exposed to excessive insulin, such as infants of diabetic mothers. Children with diabetes are also at risk, when their therapy with insulin may at times be excessive, leading to hypoglycaemia and impaired glucose availability for the brain. This proposal is examining at the cellular level the mechanisms involved in loss of brain cells in the face of glucose starvation in these various conditions. We are using several in vitro models where we can grow segments of developing mouse brain or human nerve cells in a dish, compared to studies with mice subjected to low blood glucose (hypoglycemia). After establishing that our laboratory models are representative of the whole animal, we will explore the cellular mechanisms involved in neuronal death following hypoglycaemia, particularly the interaction between the insulin-like growth factor (IGF) and other cell survival genes. We will also examine the possibility that treatment with IGF will reduce the loss of nerves in the brain after an episode of hypoglycemia. This may offer new and effective early treatment for this damaging brain injury in both newborn babies and children with insulin-dependent diabetes.Read moreRead less
Understanding How Sepsis Causes Kidney Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$471,770.00
Summary
Acute renal failure is a serious condition that affects up to 20% of patients in Intensive Care Units. Sepsis and septic shock remain the most important causes of acute renal failure in critically ill patients. Despite our ability to support vital organs and resuscitate patients, the incidence and mortality of septic acute renal failure remain unacceptably high at up to 55%. There have been no major advances in our understanding of its pathogenesis and in its prevention or treatment over the las ....Acute renal failure is a serious condition that affects up to 20% of patients in Intensive Care Units. Sepsis and septic shock remain the most important causes of acute renal failure in critically ill patients. Despite our ability to support vital organs and resuscitate patients, the incidence and mortality of septic acute renal failure remain unacceptably high at up to 55%. There have been no major advances in our understanding of its pathogenesis and in its prevention or treatment over the last 50 years. The traditional view is that sepsis-induced renal failure results from reduced perfusion of the kidney secondary to the low blood pressure. In a model of sepsis in sheep with renal failure, we demonstrated, however, that renal blood vessels dilated and blood flow increased. Furthermore, renal function improved following treatment with vasoconstrictor drugs that raised blood pressure and renal blood flow. These findings indicate that renal ischaemia is not the cause of the renal dysfunction in sepsis. We hypothesise that sepsis causes renal vasodilatation, which reduces glomerular filtration rate and renal function, and induces a delayed development of apopotosis. We will study in sepsis 1) the effects of a treatment to increase glomerular filtration rate 2) the development of apoptosis and the effect of an anti-apoptotic drug, and 3) whether there is bioenergetic failure in the kidney in sepsis and the effects of treatments on this. Finally, in septic patients we will measure renal blood flow and determine the effects of our novel treatment on this and renal function. These studies will significantly increase our understanding of the factors causing acute renal failure in sepsis. They are likely to lead to the development of new therapies to improve renal function in sepsis and their effectiveness will be examined in septic animals and patients.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