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Research Topic : Vascular function
Scheme : NHMRC Development Grants
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  • Funded Activity

    The Effect Of Stress/strain And Fatigue Fracture Sites On Durability Of Modular Aortic Endografts And Arterial Walls

    Funder
    National Health and Medical Research Council
    Funding Amount
    $300,919.00
    Summary
    Aneurysmal disease is an age related phenomenon. The mean life expectancy of western populations has doubled in 100 years because of the reduction in deaths from preventable and treatable diseases, and prolongation of life with chronic and incurable diseases. The older community (>65 years) continues to be active and productive contrary to prior predictions. Aneurysmal disease has emerged as a result of the changing pattern of diseases in the community. As with many other diseases, prophylaxi .... Aneurysmal disease is an age related phenomenon. The mean life expectancy of western populations has doubled in 100 years because of the reduction in deaths from preventable and treatable diseases, and prolongation of life with chronic and incurable diseases. The older community (>65 years) continues to be active and productive contrary to prior predictions. Aneurysmal disease has emerged as a result of the changing pattern of diseases in the community. As with many other diseases, prophylaxis against aneurysmal disease is the most effective approach since 80% of those that rupture will result in death. Endoluminal grafting provides a much less invasive procedure and provides an attractive and elegant alternative to open surgery. The danger is that structural strengths will be compromised with failures due to lack of strength and inadequate device durability. The most practical endografts are those that are built up from modules but vulnerable sites affected by fatiguing and disruptive forces are being identified, in particular where a tube divides into two outflow channels – the bifurcation - and joins. To improve and protect the current device, and enable sound engineering for future devices, we need to know the nature, magnitude and location of these forces. The existing collaboration with medical specialist, Cook Aust., the Advanced Fluid Dynamics Laboratory (CSIRO, Melb.) and University of WA combines a multidisciplinary team working towards the design and durability of the next generation of endoluminal devices and percutaneous insertions. While Australia is at the forefront of development, its current place in the market can only be maintained by further product development. Optimising and improving endoluminal grafts will reduce the suffering of major surgery while prolonging a higher quality of life with a much less invasive procedure whose long-term effectiveness, and thereby acceptance is dependent upon reliable durability.
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    Funded Activity

    Minimal Structural Strength Required In Endoluminal Devices For Aortic Aneurysms: Mechanisms Of Rupture When They Fail.

    Funder
    National Health and Medical Research Council
    Funding Amount
    $102,794.00
    Summary
    Aneurysmal disease is an age related phenomenon. The mean life expectancy of western populations has doubled in the last 100 years mainly because of the reduction in deaths from occlusive cardiovascular disease. Aneurysmal disease has emerged as a result of the changing pattern of diseases in the community. The impact of this work would be to improve minimally invasive, effective prophylaxis against aneurysm of the abdominal aorta since 80% of those that rupture will result in death. Endoluminal .... Aneurysmal disease is an age related phenomenon. The mean life expectancy of western populations has doubled in the last 100 years mainly because of the reduction in deaths from occlusive cardiovascular disease. Aneurysmal disease has emerged as a result of the changing pattern of diseases in the community. The impact of this work would be to improve minimally invasive, effective prophylaxis against aneurysm of the abdominal aorta since 80% of those that rupture will result in death. Endoluminal grafting provides a much less invasive procedure and provides an attractive and elegant alternative to open surgery. The general drive in this field is towards miniaturisation. The danger is that structural strengths will be compromised with early failures due to lack of strength; and late failures due to inadequate device durability. This application proposes the development of a collaborative venture with the Department of Vascular Surgery, Royal Perth Hospital, Cook R and D (WA), the Advanced Fluid Dynamics Laboratory (CSIRO, Melbourne) and Centre for Health Services Research (University of WA) to investigate the dynamic flow forces involved in aneurysms of the abdominal aorta. It combines together expertise and facilities to examine the forces acting upon endoluminal stent grafts in pulsatile high pressure environments, the impact on the design, patency, effectiveness and longer-term outcomes. The multidisciplinary team provides a comprehensive approach for this developing area of high technology surgery throughout Australia and internationally. The benefits of this study will directly influence the design and durability of the next generation of endoluminal devices and percutaneous insertions. While Australia is at the forefront of development, its current place in the market can only be maintained by further product development.
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    Funded Activity

    New Dynamometric Techniques For Predicting Glaucoma Progression

    Funder
    National Health and Medical Research Council
    Funding Amount
    $171,825.00
    Summary
    Glaucoma is a major cause of blindness in our community. The biggest risk factor for glaucoma is raised intraocular pressure. However, the exact cause of the disease remains unknown. Through our basic science studies in animals we have discovered that changes in blood flow in the vessels at the optic disk may be involved in the disease process. In recent clinical trials we discovered that the presence or absence of pulsations in the retinal veins at the disk was both an indicator of severity and .... Glaucoma is a major cause of blindness in our community. The biggest risk factor for glaucoma is raised intraocular pressure. However, the exact cause of the disease remains unknown. Through our basic science studies in animals we have discovered that changes in blood flow in the vessels at the optic disk may be involved in the disease process. In recent clinical trials we discovered that the presence or absence of pulsations in the retinal veins at the disk was both an indicator of severity and progression of glaucoma. This is a major breakthrough because there is no other means of predicting in which glaucoma patients vision loss will develop most rapidly. This information will be very helpful in deciding which patients should have the most agressive treatment to restore normal intraocular pressure. This project seeks to develop a new commercial device to make such an examination easy for any clinical ophthalmologist. The device allows the doctor to examine the vessels at the disk whilst applying slight pressure to the eye to temporarily raise intraocular pressure. A footswitch is pressed when the doctor sees the vessels pulsate. The required force is recorded by a laptop computer and the data stored along with the patients details. Now we have confirmed the ability of such a measurement to predict the rate of visual field loss in glaucoma, such a measurement will become much more widespread in clinical ophthalmology, offering a new and large scale opportunity for such instrumentation. Our device will be easy to operate, more comfortable for the patient, and will be of major diagnostic value in glaucoma clinics worldwide.
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    Funded Activity

    High-frequency Forced Oscillations For Diagnosing And Assessing Emphysema And COPD

    Funder
    National Health and Medical Research Council
    Funding Amount
    $115,371.00
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    Funded Activity

    External Therapeutic Device To Support Rehabilitation Of The Hand Following Trauma Or Surgery

    Funder
    National Health and Medical Research Council
    Funding Amount
    $175,000.00
    Summary
    The loss of hand function will affect every aspect of an individual’s life. This includes the ability to feed and care for themselves and the ability to work and participate in family life. For people recovering from problems such as trauma, burns or surgery affecting the hand, careful management of hand rehabilitation can influence the outcome for the patient significantly. In order to reduce the possibility of mobility difficulties occurring, including loss of joint range of motion, muscle and .... The loss of hand function will affect every aspect of an individual’s life. This includes the ability to feed and care for themselves and the ability to work and participate in family life. For people recovering from problems such as trauma, burns or surgery affecting the hand, careful management of hand rehabilitation can influence the outcome for the patient significantly. In order to reduce the possibility of mobility difficulties occurring, including loss of joint range of motion, muscle and tendon sheath adhesions or non-functional scar tissue formation, continuous passive motion (CPM) is often indicated. Additionally, for people with reduced mobility of the hand due to upper limb paralysis, such as those with cervical spinal cord injury, stroke, cerebral palsy or peripheral nerve injury, disregard for management of the maintenance of the joint range of motion of the effected hand will result in contracture and limited joint range of motion. Such syndromes will reduce hand function, which is already limited by paralysis, and will negatively affect potential outcomes for aggressive rehabilitation techniques, such as tendon transfer surgery and functional neuromuscular stimulation. Therefore, in such cases, CPM is also indicated. Current devices applying CPM have shown to be effective in minimising the syndromes indicated above and these results are summarised in the Background and Research Plan attached to this proposal. Unfortunately, the use of such devices is not always prescribed by clinicians. This is due, mainly, to the limitations of these devices that are in the marketplace. These limitations include lack of secure finger placement, lack of portability, the inability to provide specialised therapy to specific joints and inflexible programming. This proposal introduces an improved device to be developed and these improvements form the proposal aims below. Given such an improved device, which can overcome many of the problems with current CPM machines, it is likely that that the clinical application of CPM will achieve the greater degree of prescription and application in hand rehabilitation. These improvements should overcome the clinical reticence to use these devices and restore a balance by increasing their use to the level that the scientific literature indicates they should have. The overall aim of the proposal is to take the device to a stage where it is ready for clinical trial.
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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

    Studies Of Metabolites Of Synthetic Flavonols For The Treatment Of Cardiovascular Disease

    Funder
    National Health and Medical Research Council
    Funding Amount
    $207,440.00
    Summary
    Cardiovascular disease, including heart attack and stroke, is the leading killer of Australians. A promising new drug, NP202, can reduce the amount of tissue damaged from a heart attack; however, its mechanism of action remains obscure. NP202 is metabolized to a range of compounds, one of which is partly responsible for its beneficial effects. In this project we will identify other metabolites of NP202 and characterize their biological activity to gain insight into its mechanism of action.
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    Funded Activity

    Seminal Plasma Cytokines As Novel Fertility Diagnostics In Men

    Funder
    National Health and Medical Research Council
    Funding Amount
    $101,000.00
    Summary
    Infertility and recurrent miscarriage affect 60-80 million couples globally, including 15% of couples in Australia. Current IVF therapy is not successful when the underlying reason for infertility is failure of the maternal tissues to support embryo implantation. We have discovered signaling proteins present in male semen that act in the female reproductive tissues to prepare for embryo implantation and healthy pregnancy. Recently we have identified those proteins and have shown that some men ha .... Infertility and recurrent miscarriage affect 60-80 million couples globally, including 15% of couples in Australia. Current IVF therapy is not successful when the underlying reason for infertility is failure of the maternal tissues to support embryo implantation. We have discovered signaling proteins present in male semen that act in the female reproductive tissues to prepare for embryo implantation and healthy pregnancy. Recently we have identified those proteins and have shown that some men have an imbalance in seminal proteins that leads to immune rejection of the embryo in the female partner. This project aims to develop a new test for male fertility that is based on seminal plasma proteins and independent of existing sperm count tests. Furthermore we will determine whether seminal protein imbalance can result from the �silent� presence of male reproductive tract infection.
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    Funded Activity

    Acoustic Blood Pressure Measurement On Implanted Biomedical Surfaces

    Funder
    National Health and Medical Research Council
    Funding Amount
    $184,687.00
    Summary
    Measurement of local blood pressure in is of great clinical importance. An application of particular interest is the pressure measurement in and around endoluminal stents grafts, which are used for the treatment of Abdominal Aortic Aneurysms (AAAs). These grafts are implanted by keyhole surgery and are used to reduce the pressure on the aneurysm walls so that the artery can revert to its more anatomically correct shape on a timescale of one to two years. If the seal between the graft and the art .... Measurement of local blood pressure in is of great clinical importance. An application of particular interest is the pressure measurement in and around endoluminal stents grafts, which are used for the treatment of Abdominal Aortic Aneurysms (AAAs). These grafts are implanted by keyhole surgery and are used to reduce the pressure on the aneurysm walls so that the artery can revert to its more anatomically correct shape on a timescale of one to two years. If the seal between the graft and the artery wall is not blood tight, then the aneurysm can become repressurised and may keep on expanding. Over time, an untreated, expanding AAA is likely to rupture with severe consequences for the patient. Thus a convenient, non-invasive means of measuring the pressure within the aneurysm and within the graft is highly desirable. In this proposal, we seek to produce a device that can be incorporated into the walls of the endoluminal graft, which can measure absolute pressure inside and outside the graft and where the pressure measurements can be obtained via standard acoustic or medical ultrasound equipment. To do this, we would use specially designed 'bubbles' which can be incorporated onto either side of the graft walls, where the resonant frequency of the bubbles provides a direct measurement of the pressure around the bubbles. Trials at the CSIRO have found that pressures can be measured to a resolution of better than 10 mmHg by using this technique on air bubbles in water. In this proposal, we wish to develop flexible, but semi-permanent bubbles that can be incorporated onto a biomedical implant surface. If such bubbles can be made, the researchers will use CSIRO-developed software and acoustic equipment such that local blood pressure can be measured in real time.
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    Funded Activity

    Development Of Platelet-Targeted Nanoparticles For Magnetic Resonance Imaging Towards The Detection Of Thrombi/Emboli And Vulnerable Atherosclerotic Plaques

    Funder
    National Health and Medical Research Council
    Funding Amount
    $606,524.00
    Summary
    Heart attack, stroke and pulmonary embolism typically strike without warning and either kill patients or cause devastating disabilities. Currently, we do not have diagnostic methods to identify patients and the blood vessels at risk. We have developed a new innovative MRI nanoparticle directed against activated platelets for the detection of _at risk� blood vessels. The current funding is requested to optimise the manufacture of this targeted MRI nanoparticle and to undertake the animal studies .... Heart attack, stroke and pulmonary embolism typically strike without warning and either kill patients or cause devastating disabilities. Currently, we do not have diagnostic methods to identify patients and the blood vessels at risk. We have developed a new innovative MRI nanoparticle directed against activated platelets for the detection of _at risk� blood vessels. The current funding is requested to optimise the manufacture of this targeted MRI nanoparticle and to undertake the animal studies required to enter early stage clinical trials.
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