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Research Topic : Functions Of Several Complex Variables
Scheme : NHMRC Development Grants
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  • Funded Activity

    Assessment Of Bilateral Oedema By Bioelectrical Impedance Analysis

    Funder
    National Health and Medical Research Council
    Funding Amount
    $180,000.00
    Summary
    Swelling of tissue due to fluid accumulation, known as oedema, is one of the earliest signs of diseases such as kidney failure, burn injury or lymphedema. All of these are not uncommon conditions. Lymphedema, for example, is a common sequela of radiotherapy or surgery in the treatment of malignancies such as breast, uterine, and prostatic carcinoma. It is reported to occur in up to 40% of patients depending on the type of surgery and whether or not the patient received radiotherapy. It is estima .... Swelling of tissue due to fluid accumulation, known as oedema, is one of the earliest signs of diseases such as kidney failure, burn injury or lymphedema. All of these are not uncommon conditions. Lymphedema, for example, is a common sequela of radiotherapy or surgery in the treatment of malignancies such as breast, uterine, and prostatic carcinoma. It is reported to occur in up to 40% of patients depending on the type of surgery and whether or not the patient received radiotherapy. It is estimated that at any time 100000 women are suffering from post- mastectomy lymphedema in Australia alone. Treatment of breast cancer alone therefore, given the incidence of the disease, produces a large at-risk population. Add to this other causes of oedema and the magnitude of the problem becomes clearly apparent. The presence of chronic oedema is often a disfiguring and disabling disorder, usually accompanied by pain, recurrent infection, reduced mobility and impaired function. In acute oedema the problem often resolves with recovery from the underlying pathology. In chronic oedema, progression may be arrested by early intervention including complex physical therapy (exercise regimen, compression bandaging, and massage) which is effective in reducing limb volume, in improving the quality of life, function and body image of patients. Although the assessment of oedema is clearly of clinical importance, relatively few objective and accurate techniques for its measurement exist. Research conducted over the past decade by the applicants has pioneered the Use of Bioelectrical Impedance Analysis for the assessment of lymphedema. This study aims to translate this basic research into clinical practice. Sensitivity and specificity studies will establish normative and threshold values for impedance measurements that can be used as presumptive indicators of oedema. User friendly technology and equipment suitable for clinical use will be developed which should improve treatment therapies.
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    Funded Activity

    Clinical Trial Of Respiratory Sonification

    Funder
    National Health and Medical Research Council
    Funding Amount
    $100,951.00
    Summary
    We will conduct a clinical trial of the effectiveness of a continuous auditory display of an anesthetized patient's respiratory status. Expired carbon dioxide monitoring has helped reduce respiratory incidents since its widespread introduction in the late 1980s, but a continuous auditory display of respiratory status may reduce incidents further. We will conduct a clinical trial with 10 anaesthetists of continuous auditory respiratory monitoring. Successful outcome may lead to commercial uptake.
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    Funded Activity

    Development And Clinical Evaluation Of A Depth Of Anaesthesia Monitor

    Funder
    National Health and Medical Research Council
    Funding Amount
    $424,785.00
    Summary
    Waking up during surgery (awareness under anaesthesia) is a frightening reality for some patients. Although uncommon (occurring in about 1 in 1000 operations), it remains one of the main concerns of patients before their surgery. Recent studies (including our own) have demonstrated that processed EEG monitoring using bispectral index (BIS) can markedly reduce the risk of awareness. Other EEG monitors are being developed, but each have weaknesses. As approximately two million Australians have a g .... Waking up during surgery (awareness under anaesthesia) is a frightening reality for some patients. Although uncommon (occurring in about 1 in 1000 operations), it remains one of the main concerns of patients before their surgery. Recent studies (including our own) have demonstrated that processed EEG monitoring using bispectral index (BIS) can markedly reduce the risk of awareness. Other EEG monitors are being developed, but each have weaknesses. As approximately two million Australians have a general anaesthetic each year, about 2000 will suffer an episode of awareness. More than 60 million people around the world have an anaesthetic, and so the problem is substantial. This suggests the potential benefits (health outcomes, commercial gains) are very great. In 2000 less than 5% of US hospitals used BIS monitoring; the current figure in the US is about 69% of the best-rated hospitals (US News and World Report) and 78% of teaching hospitals. A similar rapid growth is occurring in Australia and Europe. We are working with a successful Australian Company (Compumedics Ltd) to develop a better awareness monitor. We plan studies in groups of patients have surgery.
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    Funded Activity

    A Novel Treatment For Ameliorating Retinal Vascular Disease

    Funder
    National Health and Medical Research Council
    Funding Amount
    $366,685.00
    Summary
    Retinal vascular disease is a leading cause of blindness and is currently treated by laser photocoagulation surgery. Although successful, this treatment is associated with serious side effects. Recently, Ellex Pty has developed a novel laser called the 2RT laser that is likely to be effective without the accompanying side effects. This study will allow examine the effect of the 2RT laser in animal models of retinal vascular disease so as to complete preclinical development of this laser.
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    Funded Activity

    Proof Of Principle Of The Activation Of Anthracycline Anticancer Agents By Formaldehyde-releasing Prodrugs In Mouse Xeno

    Funder
    National Health and Medical Research Council
    Funding Amount
    $208,350.00
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    Funded Activity

    Development Of A Smart Arthroscopy System And Prototype Probe For Joint Tissues

    Funder
    National Health and Medical Research Council
    Funding Amount
    $230,632.00
    Summary
    This project relates to the ever growing use of arthroscopy in the management of joint defects. An innovative probe that will combine all the molecular, microstructural and biomechanical characteristics of joint articular cartialge and bone for the purposes of diagnosis, treatment, treatment-related decisions, comparison of the effectiveness of treament methods and post treatment evaluation will be developed. This system will produce spin-offs for artrhoscopy of other soft tissues and bodies.
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    Funded Activity

    Development And Evaluation Of Novel Anti-inflammatory Products Derived From An Indigenous Medicinal Plant

    Funder
    National Health and Medical Research Council
    Funding Amount
    $276,598.00
    Summary
    This collaborative project between researchers at the University of South Australia and Indigenous traditional owners from Northern Kaanju homelands (Cape York Peninsula, Qld) will develop and evaluate products derived from the Northern Kaanju medicinal plant Dodonaea polyandra. Extracts of the plant and novel compounds isolated from it have anti-inflammatory activity. These have the potential to be used in inflammatory diseases such as dermatitis, arthritis and inflammatory bowel disease.
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    Funded Activity

    Development Of Anti-metastatic And Tumour Targeting Reagents By Design Of Inhibitors To Specific Eph/ephrin Cell-cell

    Funder
    National Health and Medical Research Council
    Funding Amount
    $200,000.00
    Summary
    Metastatic disease, malignant melanoma in particular, is a health issue of considerable global importance with 1,000 fatal melanoma cases- year in Australia alone. While progress has been made on prevention and early diagnosis, no curative treatment exists for stage IV melanoma. Tumour progression and the acquisition of metastatic competence primarily reflect dysregulation of cell adhesion and cell motility rather than proliferation and survival. In this context, Eph receptor tyrosine kinases (E .... Metastatic disease, malignant melanoma in particular, is a health issue of considerable global importance with 1,000 fatal melanoma cases- year in Australia alone. While progress has been made on prevention and early diagnosis, no curative treatment exists for stage IV melanoma. Tumour progression and the acquisition of metastatic competence primarily reflect dysregulation of cell adhesion and cell motility rather than proliferation and survival. In this context, Eph receptor tyrosine kinases (Ephs) and their membrane-bound ephrin ligands are crucial mediators of cell adhesion and motility and are notably overexpressed in metastatic tumours rather than primary (benign) lesions5. Our laboratories were the first to identify EphA3 7, and one of the first to isolate its ligand, ephrin-A5. EphA3 was isolated from acute lymphoblastoid leukemia and malignant melanoma patients, where increasing expression levels correlate with metastatic progression. Soluble, non-clustered forms of Ephs and ephrins are effective inhibitors of Eph activity 3 and provide opportunities to generate specific drugs for cancer therapy. We now propose a research and development program for the development of EphA3-specific drugs and their production for pre-clinical and clinical evaluation for placement onto a national and international market.
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    Funded Activity

    Stage II In The Development Of Eph/ephrin Based Tumor Targeting Reagents: Optimisation Of Drug Efficacy And Delivery

    Funder
    National Health and Medical Research Council
    Funding Amount
    $204,125.00
    Summary
    In the final stage of cancer, including melanoma, tumor cells gain the ability to spread, a process called metastasis. Altered communication between cancer and normal cells is one of the causes of this invasive characteristic. We have started the development of novel agents that target and modulate proteins on the cell surface that control these properties and are found in metastatic tumors. We propose to refine the targeting and killing properties of these agents for early clinical testing.
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    Funded Activity

    Therapeutic Strategies And Screening Methods For PKC Epsilon Antagonists In The Treatment Of Type 2 Diabetes

    Funder
    National Health and Medical Research Council
    Funding Amount
    $157,375.00
    Summary
    Type 2 diabetes is a chronic disease affecting over a million Australians and hundreds of millions of people worldwide. Its prevalence is rising due to several factors such as an increase in caloric intake, the aging of the population, and the common sedentary lifestyle of Western civilization. Type 2 diabetes occurs when the pancreas is unable to produce enough insulin for the body to cope with rising blood glucose levels after a meal, and has been strongly linked to obesity. We have now shown .... Type 2 diabetes is a chronic disease affecting over a million Australians and hundreds of millions of people worldwide. Its prevalence is rising due to several factors such as an increase in caloric intake, the aging of the population, and the common sedentary lifestyle of Western civilization. Type 2 diabetes occurs when the pancreas is unable to produce enough insulin for the body to cope with rising blood glucose levels after a meal, and has been strongly linked to obesity. We have now shown that an enzyme found in the pancreas becomes inappropriately activated under conditions of fat oversupply, and plays an important role in the development of defects in insulin release from the pancreas in response to glucose. Excitingly, we have also shown that inhibition of this enzyme can partly reverse these defects once they have been established. We now intend to further validate this enzyme as a drug target by determining the optimum dosing regimen for the treatment of type 2 diabetes in a mouse model, and testing whether this approach can be used in conjunction with previously-developed drugs which promote insulin action, to improve bood glucose handling better than either treatment alone. This would promote the enzyme as a therapeutic strategy in the treatment of Type 2 diabetes. We also plan to develop a high throuhput screen to identify novel inhibitors of the enzyme, which will further increase the attractiveness of the project to pharmaceutical companies, who are better able to implent full commercialization of our findings.
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