Randomised Trial Of Continuity Of Nursing Care In Vascular Surgery
Funder
National Health and Medical Research Council
Funding Amount
$190,648.00
Summary
Both overseas (Bruni, Hoosier-Paty and Hoffman 1996) and in Australia (Norman, Semmens, Laurence-Brown and Holman, under review), surgeons have become increasingly aware of the need to improve outcomes for patients undergoing arterial surgery for the lower limb. Unlike other areas of health care reform such as cardiac surgery or breast cancer, there is little confidence that the current links between acute facilities, community-based health services and general practice, work optimally together. ....Both overseas (Bruni, Hoosier-Paty and Hoffman 1996) and in Australia (Norman, Semmens, Laurence-Brown and Holman, under review), surgeons have become increasingly aware of the need to improve outcomes for patients undergoing arterial surgery for the lower limb. Unlike other areas of health care reform such as cardiac surgery or breast cancer, there is little confidence that the current links between acute facilities, community-based health services and general practice, work optimally together. Peripheral vascular disease is rarely studied. In NSW, there are about 4200 inpatient episodes for arterial surgery for ischaemia of the lower limb each year (AN-DRG 228 - 232), the majority involving older men. This study brings together a multi-disciplinary team of CIs comprising an academic nurse, two vascular surgeons and an expert in outcomes evaluation to conduct a randomised trial (n-586) of continuity of nursing care for patients admitted for arterial surgery of the lower limb. The intervention is comprised of a 'Patient Stay' Flowchart, continuing postoperative in-patient nursing assessment and staff consultation, Patient Education Discharge Booklet, Patient - Family Care Plan; proactive and reactive telephone follow-up and extensive GP liaison. Blinded outcome evaluation at six and twelve months will compare its differential effectiveness against usual care to which only the Patient Stay' Flowchart has been added. We will generate Level 2 evidence for the effectiveness of continuity of nursing care in improving outcomes for patients undergoing arterial surgery for ischaemia of the lower limb. To our knowledge, this would be the first Australian efficacy trial of its type.Read moreRead less
Early Events In Arteriolar Remodeling: Adaptation To Prolonged Vasoconstriction
Funder
National Health and Medical Research Council
Funding Amount
$415,750.00
Summary
Small arteries, while acutely responding to their environment with changes in diameter to regulate local blood flow and pressure, also undergo structural adaptation or remodelling. These events occur over a range of time-frames and involve both non-genetically and genetically regulated events. Thus a contractile event, while initially decreasing vessel diameter, also activates longer time frame processes which can span from rearrangment of cellular junctions-contacts to overt structural changes ....Small arteries, while acutely responding to their environment with changes in diameter to regulate local blood flow and pressure, also undergo structural adaptation or remodelling. These events occur over a range of time-frames and involve both non-genetically and genetically regulated events. Thus a contractile event, while initially decreasing vessel diameter, also activates longer time frame processes which can span from rearrangment of cellular junctions-contacts to overt structural changes within the vessel wall (for example thickening of the muscle layer). These adaptive processes may enable the forces of contraction to be maintained without continued energy expenditure and damage to the vessel per se. However, they can also contribute to long-term alterations in the control of blood pressure and perhaps contribute to states of hypertension as well as other common vascular diseases. For these studies we will use arterioles, isolated by microsurgical techniques, together with sophisticated computer and video-based approaches. These techniques allow arterioles to be studied under controlled conditions and relevant biochemical measurements performed. We will also use a cell model where cultured cells will be studied after defined periods of mechanical stimulation (for example stretch). Cells will be probed using a novel microscopic technique (atomic force microscopy) which enables the cell membrane to be studied with respect to changes in composition as well as physical characteristics (for example stiffness). The studies are relevant to our understanding of the normal adaptive processes occurring within blood vessels to control blood flow and pressure. The studies are also of direct relevance to our understanding of common vascular disease states including hypertension, complications of diabetes and chronic inflammatory disorders.Read moreRead less
How Does Activated Protein C Create Intact, Non-leaky, Stable Blood Vessels?
Funder
National Health and Medical Research Council
Funding Amount
$564,644.00
Summary
Vascular dysfunction is a common feature of many diseases, including sepsis, diabetes, atherosclerosis, tumours and asthma. These vessels have compromised structural and functional integrity, leading to leakage of blood components and causing inflammation in tissues. Based on our recent findings, this project aims to discover how activated protein C creates normal, healthy non-leaky blood vessels and prevents vascular dysfunction in disease.
Local Microvascular Regulatory Mechanisms In Diabetes: Relevance To Neuropathy
Funder
National Health and Medical Research Council
Funding Amount
$212,036.00
Summary
In diabetes mellitus, the excessive levels of sugar in the blood may cause changes in metabolic processes within cells that lead to disturbances in the function of the circulatory and nervous systems. Such disturbances have been shown to occur in the early stages of diabetes and ultimately lead to longterm consequences including poor wound healing (often culminating in limb amputations), increased risk of blindness, kidney disease and heart failure. At present it is not possible to restore norma ....In diabetes mellitus, the excessive levels of sugar in the blood may cause changes in metabolic processes within cells that lead to disturbances in the function of the circulatory and nervous systems. Such disturbances have been shown to occur in the early stages of diabetes and ultimately lead to longterm consequences including poor wound healing (often culminating in limb amputations), increased risk of blindness, kidney disease and heart failure. At present it is not possible to restore normal metabolism, leaving patients at risk of developing complications involving the circulatory and nervous systems. An understanding of the processes involved in the development of such complications would allow alternate treatment strategies to be devised in order to improve the quality of life and life expectancy of diabetic patients. The events leading to abnormalities in the function of the circulatory and nervous systems are uncertain, however, studies have demonstrated that in diabetes there may be an insufficient blood supply to nerves and this would be expected to cause nerve damage. At present, our understanding of the factors involved in regulating blood flow to nerves is limited. The studies described in this proposal are aimed at testing the hypothesis that nerve blood vessels are themselves involved in the regulation of flow through an intrinsic ability to change their diameter in response to tissue demands and that in diabetes alterations in the capacity of nerve blood vessels to constrict or dilate compromises their role in the control of nerve blood flow . Information obtained from these studies will improve our understanding of the early disturbances in the function of circulatory and nervous systems leading to alterations in blood flow which precede the development of overt changes characteristic of the complications associated with diabetes. This will provide insight into developing new treatment strategies for diabetic patients.Read moreRead less
Antioxidant Glutathione Peroxidase (GPx) Mimetics And Atherosclerosis: A Role For Targeted Antioxidant Therapy.
Funder
National Health and Medical Research Council
Funding Amount
$358,319.00
Summary
This proposal investigates the use of antioxidant therapy, targeted at increasing the function of the body's important antioxidant enzyme GPx1, to reduce atherosclerosis both in a non-diabetic and diabetic setting. Strong clinical evidence and our recently published data support an important role for GPx1 in limiting atherosclerosis. We will now investigate the molecular mechanisms involved in mediating these effects and whether compounds that mimic GPx1 function reduce atherosclerosis.
Vascular And Neuro-glial Dysfunction In Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$481,500.00
Summary
The retina is responsible for sight. Vision occurs by interactions between blood vessels, neurons (cells that transmit electrical signals for vision) and glia (cells that support the retina). In diabetes, high amounts of glucose in blood increases certain factors within retinal cells. These factors slowly cause damage, such that after 15 years of diabetes all patients will have some retinal disease and many will loose sight. Indeed, diabetes is the leading cause of blindness in working people. T ....The retina is responsible for sight. Vision occurs by interactions between blood vessels, neurons (cells that transmit electrical signals for vision) and glia (cells that support the retina). In diabetes, high amounts of glucose in blood increases certain factors within retinal cells. These factors slowly cause damage, such that after 15 years of diabetes all patients will have some retinal disease and many will loose sight. Indeed, diabetes is the leading cause of blindness in working people. The main treatment for diabetic retinal disease is to burn away damaged blood vessels, however, this treatment has problems. Firstly, the burns destroy healthy retina and the disease continues, secondly, the treatment is performed late in the disease and therefore does not prevent the early changes in retinal cells, and thirdly, changes in neurons and glia are often not considered. Therefore, there is an urgent need to understand how blood vessels, neurons and glia interact with each other to threaten vision in diabetes, with the intention of developing safer and more effective treatments. This will be the focus of the current project. Currently, there are no studies that have examined the sequential changes in retinal blood vessels, neurons and glia in diabetes. This is mainly due to the lack of an experimental rodent model that progresses from mild to severe diabetic retinal disease. In 2003, we established such a model in the diabetic Ren-2 rat. In this project the diabetic Ren-2 rat will be used to study retinal cell changes and also to identify the factors that damage these cells. We suggest that angiotensin, bradykinin and VEGF are involved. These factors are present in the normal retina and are increased in diabetes. We will block these factors with specific drugs with the intention of understanding how these factors affect retinal cells in diabetes, and also to develop new drug therapies for the treatment of both early and late diabetic retinal disease.Read moreRead less
Our studies are aimed at examining how blood flow and pressure is controlled in the various tissues of the body. In particular, we hope to improve our understanding of how blood flow is matched to local metabolic requirements and how a constancy of conditions can be maintained despite changes in overall blood pressure. This ability to control local blood flow occurs through the ability of very small arteries to rapidly adjust their diameters through vasoconstriction or vasodilatation. The vessel ....Our studies are aimed at examining how blood flow and pressure is controlled in the various tissues of the body. In particular, we hope to improve our understanding of how blood flow is matched to local metabolic requirements and how a constancy of conditions can be maintained despite changes in overall blood pressure. This ability to control local blood flow occurs through the ability of very small arteries to rapidly adjust their diameters through vasoconstriction or vasodilatation. The vessels can thus act as valves regulating the transfer of blood flow and pressure to smaller vessels downstream. One particular response that small arteries exhibit is the ability to constrict when pressure within the vessels increases. The increase in pressure appears to stretch the vessel wall which in turn initiates a series of mechanical and biochemical steps that ultimately lead to contraction of muscle cells within the vessel wall. By contracting, the vessels limit the increase in downstream flow and pressure that would be expected to occur. The vessels being studied are very small, typically less than 100 micron. They are studied under isolated and controlled conditions using microscope and computer-based imaging techniques. While this allows us to directly monitor changes in vessel diameter to various stimuli (e.g. a change in pressure) we have also had to miniaturize biochemical measurements so we can understand the chemistry which underlies these vasoconstrictor responses. Understanding of how these local blood regulatory mechanisms occur is not only relevant to our understanding of the normal situation but is also vital to understanding disease states. For example, this work is very relevant to common cardiovascular disorders such as hypertension. It is hoped that a detailed understanding of the biochemical pathways by which small arteries contract will allow the design and targeting of pharmaceutical approaches for treatment of vascular disease states.Read moreRead less
Atherosclerosis (hardening of the arteries) is the principal cause of heart attack, stroke and blockage of blood flow to the lower limbs. However, to date none of the biological or synthetic grafts used to bypass the narrowed regions of arteries is ideal. We have shown that lengths of silicone tubing placed into the peritoneal cavity of rats or rabbits becomes covered within 2 weeks by a capsule of granulation tissue (smooth-muscle-like cells and collagen) and mesothelial (endothelial-like) cell ....Atherosclerosis (hardening of the arteries) is the principal cause of heart attack, stroke and blockage of blood flow to the lower limbs. However, to date none of the biological or synthetic grafts used to bypass the narrowed regions of arteries is ideal. We have shown that lengths of silicone tubing placed into the peritoneal cavity of rats or rabbits becomes covered within 2 weeks by a capsule of granulation tissue (smooth-muscle-like cells and collagen) and mesothelial (endothelial-like) cells. The silicone tubing can be removed and the tissue turned inside out such that the endothelial-like cells now line the inside of the tube of living tissue, which resembles a blood vessel. These artificial blood vessels will be grown in the peritoneal cavity of rabbits, then grafted into the right carotid artery to replace a length of removed vessel. Their long-term (3,6,9 and 12 months) patency, reactivity, tensile strength and resistance to clot development will be assessed. Their susceptibility to atherosclerotic plaque development and blockage (as compared with natural carotid artery) will be examined in rabbits fed a cholesterol-enriched diet. Changes in gene expression as the artificial artery progressively develops will be examined, as will the potential to genetically manipulate the artificial artery to improve its functioning. Finally, attempts will be made to grow the vessels entirely in vitro. This novel vascular graft may open new options in the field of arterial reconstructive surgery for replacing or bypassing diseased vessels or as an access vessel for haemodialysis patients with end stage renal failure. This study will also provide new information on the biology of cells found in the peritoneal cavity and their alternative pathways for differentiation.Read moreRead less
Exertional Dyspnoea With Increased Filling Pressure - Mechanisms And Treatment Strategies
Funder
National Health and Medical Research Council
Funding Amount
$387,793.00
Summary
Patients with early heart disease often present with shortness of breath with exercise, as myocardial reserve at that stage is usually sufficient to maintain normal function at rest . Indeed, much myocardial dysfunction may originate from the modern lifestyle, including inactivity, obesity, the metabolic syndrome and type II diabetes. The potential benefits of making a definitive early diagnosis are large, because it seems more likely that an impact can be made on the disease process (and theref ....Patients with early heart disease often present with shortness of breath with exercise, as myocardial reserve at that stage is usually sufficient to maintain normal function at rest . Indeed, much myocardial dysfunction may originate from the modern lifestyle, including inactivity, obesity, the metabolic syndrome and type II diabetes. The potential benefits of making a definitive early diagnosis are large, because it seems more likely that an impact can be made on the disease process (and therefore, outcome) than with late stage disease. Current treatment strategies are expensive and because they are directed at end-organ damage (heart failure, heart attacks etc), rather ineffective. This multispecialty, multidisciplinary group will undertake a series of unique studies aimed at identifying early cardiovascular disease. The strategy will involve detection of abnormal filling behaviour at stress echocardiography, with randomization into longterm and short-term trials to examine various therapeutic strategies. Sensitive new cardiovascular imaging techniques will be used to detect preclinical abnormalities in the structure and function of the heart and vasculature, facilitating a mechanistic understanding of the process of increasing filling pressure with exercise.Read moreRead less
Oxidative Stress, Heparan Sulfates And Endothelial Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$450,390.00
Summary
During vascular disease endothelial cells that line the blood lumen are dysfunctional. Growing evidence indicates a role for a protein that the immune system normally uses to destroy infectious agents. This protein accumulates in diseased blood vessels next to endothelial cells. This project will study how this protein causes endothelial dysfunction and test the ability of novel agents to remove this protein from diseased blood vessels to improve endothelial function.