Inter-rater Reliability And Predictive Validity Of A New Functional Capacity Evaluation For Chronic Back Pain
Funder
National Health and Medical Research Council
Funding Amount
$105,794.00
Summary
Back pain costs the Australian community tens of billions of dollars. Back pain is one of the main causes of work injury and lost time from work. The longer a person is off work, the harder it is to get them back to work. Workers' compensation systems around Australia aim at getting the injured worker with back pain back to work as soon as possible. One of the difficulties in this process is determining what the person with back pain can physically do in the workplace. An evaluation technique, c ....Back pain costs the Australian community tens of billions of dollars. Back pain is one of the main causes of work injury and lost time from work. The longer a person is off work, the harder it is to get them back to work. Workers' compensation systems around Australia aim at getting the injured worker with back pain back to work as soon as possible. One of the difficulties in this process is determining what the person with back pain can physically do in the workplace. An evaluation technique, called functional capacity evaluation (known as FCE), is one method used to find out what the person with back pain physically can and cannot do. In a FCE, a trained health professional such as an occupational therapist, observes the person performing a range of physical activities like the ones he or she may have to perform in a job. The therapist closely observes the person performing activities such as lifting, carrying, kneeling, crouching, balancing, and walking and notes any limitations in the person's ability to complete the activities. The therapist makes comments about what difficulties the person may have on the job and recommendations about how these could be reduced or eliminated. The information gained from these evaluations can be valuable for the treating doctor in deciding whether the person is ready to go back to work and what duties the person can and cannot do on the job. Because of such value they provide, FCE is commonly used in rehabilitation programs endorsed by workers' compensation systems around Australia. This widespread use and endorsement of FCE occurs despite limited research on the soundness of the ratings made from these evaluations. There is a need to see whether recommendations made from FCEs are consistent between therapists (i.e. reliable) and to see if the FCE accurately predicts the person's physical capacity for work. This research will examine these issues with injured workers with back pain.Read moreRead less
Molecular Mechanisms Of Human Cytochrome P450 CYP3A4 Gene Regulation
Funder
National Health and Medical Research Council
Funding Amount
$196,059.00
Summary
Liver cytochrome P450 enzymes are important to medicine in areas as broad as drug breakdown, steroid hormone regulation and the formation or elimination of cancer causing chemicals. These enzymes are present in high concentration in the human liver, but the factors governing how much of these enzymes are produced have been poorly understood. Cytochrome P450 3A4 (CYP3A4) is arguably the single most important factor is how humans handle therapeutic drugs. It has been estimated that over 60% of all ....Liver cytochrome P450 enzymes are important to medicine in areas as broad as drug breakdown, steroid hormone regulation and the formation or elimination of cancer causing chemicals. These enzymes are present in high concentration in the human liver, but the factors governing how much of these enzymes are produced have been poorly understood. Cytochrome P450 3A4 (CYP3A4) is arguably the single most important factor is how humans handle therapeutic drugs. It has been estimated that over 60% of all drugs presently on the market are broken down, either in full or in part, by this enzyme. The amounts of CYP3A4 expressed in the liver differs markedly between individuals, and explains a great deal of the large variation in the way people break down drugs. Also, variations in the levels of CYP3A4 in the liver may be an important factor in both prostate cancer (the most common cancer in men) and the risk of developing leukemia after receiving chemotherapy for other cancers. The present projects builds on discoveries concerning the regulation of cytochrome P450 enzymes made by our group over the last few years, including an in-depth understanding of the way the production of CYP3A4 is increased by some drugs. In this project we seek to understand why individuals differ so much in terms of the amount of CYP3A4 in the liver (up to 10-fold) and why this enzyme is predominantly expressed in the liver and to as lesser extent, the intestine, while not being found at all in many other tissues. An understanding of these issues will allow us to: Y predict how patients will respond to drugs (pharmacogenetic testing). Y determine susceptibility to certain diseases (e.g., prostate cancer). Y develop novel drugs that can influence CYP3A4 production in the liverRead moreRead less
A Novel Procedure For Efficacious Gonadotrophin-free Infertility Treatment
Funder
National Health and Medical Research Council
Funding Amount
$436,328.00
Summary
Infertility is common and is associated with health risks and is expensive. Using laboratory animals, we have developed a unique procedure, which has comparable success rates to IVF but crucially, it eliminates the need for ovarian hormone therapy used in IVF. A clinical trial using this method has started in Brussels and in this project we will examine cells from that trial and from animals to investigate the underlying mechanisms to enable safe and rapid clinical implementation.
INTER-ETHNIC DIFFERENCES IN TOLERANCE OF ANTI-CANCER DRUGS
Funder
National Health and Medical Research Council
Funding Amount
$345,894.00
Summary
In 2 previous studies we have shown that Asian cancer patients experience more side-effects than their Caucasian counterparts when treated with the same dose and schedule of treatment. This does not appear to be related to any difference in size. We wish to explain this difference as it may avoid Asian patients receiving overdoses of treatment. Possible causes include dietary and nutritional differences
One in five Australian couples experience infertility and poor egg quality is a major contributing factor. Developing eggs in the ovary are surrounded by helper cells and we have discovered a new form of communication between these cells and the egg that regulates egg quality. This project will investigate the details of this dialogue and how it improves egg quality. New knowledge gained from this project will improve our understanding and treatment of infertility and reproductive diseases.
Defining Stromal-Cancer Cell Interactions For Xenografting Human Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$559,635.00
Summary
Prostate Cancer research continues to be hindered by a lack of laboratory models to understand disease progression and design new drugs to cure the disease. In this study, we propose to use a new and reliable method of growing human prostate cancer tissue in mice. Using this model, we will investigate the role of hormone signalling and cellular communication in prostate cancer that may lead to new therapies for men diagnosed with organ-confined disease.
Dissecting The Function Of The Hedgehog-Patched Pathway In Breast Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$606,811.00
Summary
There have been significant improvements in survival from breast cancer, particularly due to specialised treatments that target faulty pathways in the growth of cancer cells. One newly described, aggressive type of breast cancer called basal-like breast cancer lacks specialised treatment. We will determine whether the 'Hedgehog' signalling pathway is a suitable target for basal breast cancer therapy.
Bile Acid Detoxification By Nuclear Receptor-mediated CYP3A Regulation
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
Liver diseases in which there is obstruction to bile flow (cholestatic liver diseases) can lead to liver failure, liver cirrhosis as well as a diminished quality of life. Patients suffer from severe itching which may prove difficult to control. It is thought that many of these adverse effects of obstructed bile flow are due to the retention of a component of bile, called bile acids, within the body. Bile acids are detergent-like compounds formed from cholesterol. Some bile acids are highly toxic ....Liver diseases in which there is obstruction to bile flow (cholestatic liver diseases) can lead to liver failure, liver cirrhosis as well as a diminished quality of life. Patients suffer from severe itching which may prove difficult to control. It is thought that many of these adverse effects of obstructed bile flow are due to the retention of a component of bile, called bile acids, within the body. Bile acids are detergent-like compounds formed from cholesterol. Some bile acids are highly toxic and cause the death of cells in the liver if their concentration becomes too high. Evidence has emerged that the body has control mechanisms to try and combat rising levels of bile acids in cholestatic liver diseases. One such mechanism, which is the subject of this application, is the metabolism of bile acids to less toxic forms, by a process called hydroxylation. A particular class of liver enzymes, known as cytochromes P450 CYP3As, appear to mediate these hydroxylation reactions. Liver cytochrome P450 enzymes are important to medicine in areas as broad as drug breakdown, steroid hormone regulation and the formation or elimination of cancer causing chemicals. These enzymes are present in high concentration in the human liver, but the factors governing how much of these enzymes are produced have been poorly understood. The present projects builds on discoveries concerning the regulation of cytochrome P450 enzymes made by our group over the last few years, including an in-depth understanding of the way the production of CYP3As are increased by some drugs. We intend to determine the mechanism by which bile acids increase the level of CYP3A enzymes are how effective these enzymes are in hydroxylating bile acids. An understanding of these issues will allow us to better manage patents with cholestatic liver diseases and develop new strategies for treating these diseases, for example, development of novel drugs that increase bile acid hydroxylation in the liver.Read moreRead less
Novel Compounds For Use As Inhibitors Of Virulence Of Human Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$220,500.00
Summary
There is growing concern over the emergence of multi-drug resistant strains of bacteria which are no longer treatable with the current generation of antibiotics. This highlights the urgent need for development of the next generation of therapeutic agents to supplement or replace the current antibiotics. Our research team has identified a class of compounds which are naturally produced by a marine alga that may be effective in the control of bacterial pathogens. These compounds work by interferin ....There is growing concern over the emergence of multi-drug resistant strains of bacteria which are no longer treatable with the current generation of antibiotics. This highlights the urgent need for development of the next generation of therapeutic agents to supplement or replace the current antibiotics. Our research team has identified a class of compounds which are naturally produced by a marine alga that may be effective in the control of bacterial pathogens. These compounds work by interfering with the way many pathogens regulate the production of virulence traits. Some bacteria are able to signal members of their population by the specific uptake and recognition, through a receptor protein, of chemical cues they secrete into the environment. Accumulation of these cues or signals triggers expression of the genes that code for the virulence traits. Moreover, one particular class of these signal response proteins has been identified in many pathogens and has been shown to regulate protease production and production of a protective extracellular slime layer called a capsule. If one or more of these traits can be blocked, then the virulence of the bacterium can be reduced. We have preliminary data which demonstrates that the algal compounds do in fact prevent the expression of virulence traits and thus should be useful as new agents for the treatment of disease. The causative agents of cholera and severe gatroenteritis, Vibrio cholerae and V. parahaemolyticus respectively, have one or the other of these virulence traits, but the pathogen Vibrio vulnificus has all three and therefore is an excellent model pathogen. We propose to explore the ability of the algal compounds to specifically shut down expression of virulence factors with a long term aim for the development of these compounds as novel antimicrobial therapies for the post-antibiotic era.Read moreRead less