Open-label Randomised Trial Of Tolvaptan Versus Fluid Restriction In Hospitalised Patients With Moderate-severe Hyponatraemia
Funder
National Health and Medical Research Council
Funding Amount
$132,743.00
Summary
Low blood sodium level, known as hyponatraemia, is the most common electrolyte problem. It occurs in 15% of hospital patients, and can cause confusion, seizure and fatal brain swelling. Standard treatment for hyponatraemia is limiting oral fluid, but this is slow and not always effective. The drug tolvaptan works in mild hyponatraemia, but hasn't been formally tested in severe cases. We will compare benefits and risks of tolvaptan versus fluid restriction in patients with severe hyponatremia.
A Randomised Controlled Trial Of A Fluid Containing 140mmol/L Of Sodium Compared To A Fluid Containing 77mmol/L Of Sodium For Maintenance Intravenous Fluid Therapy In Hospitalised Children.
Funder
National Health and Medical Research Council
Funding Amount
$183,959.00
Summary
Intravenous fluid therapy is one of the most common and important treatments for children in hospital. In spite of this we know very little about what fluid should be used and there is now good evidence that children are experiencing adverse outcomes because of fluid treatment. The aim of this trial is to determine which intravenous fluid is best in children. It will be the largest and most relevant intravenous fluid trial performed in children. The results will have an immediate impact on treat ....Intravenous fluid therapy is one of the most common and important treatments for children in hospital. In spite of this we know very little about what fluid should be used and there is now good evidence that children are experiencing adverse outcomes because of fluid treatment. The aim of this trial is to determine which intravenous fluid is best in children. It will be the largest and most relevant intravenous fluid trial performed in children. The results will have an immediate impact on treating children worldwide.Read moreRead less
Lung Injury: Influence Of Sodium, Water, Albumin, Gravity And Body Position
Funder
National Health and Medical Research Council
Funding Amount
$117,331.00
Summary
Although patients with poor oxygenation often require mechanical ventilation, only therapies that reduce lung damage improve outcome whereas therapies that improve oxygenation have not been shown to improve outcome. This project will examine the role of two common interventions in critically ill patients, fluid resuscitation and posture change, on lung injury. It is anticipated this will lead to clinical trials that will further improve survival in ventilated patients with respiratory failure.
Acute Exercise And Digoxin Effects On Skeletal Muscle Na+,K+ATPase Regulation, K+ Homeostasis And Fatigue In Humans:
Funder
National Health and Medical Research Council
Funding Amount
$177,000.00
Summary
This grant investigates the regulation of an enzyme in skeletal muscle referred to as the sodium-potassium pump, since its function is to pump potassium into the cell and sodium out of the cell. This enzyme is vital in enabling the muscles to contract and plays a key role in supporting our capacity to exercise. Our studies have suggested that acute exercise depresses the maximal capacity (activity) of this enzyme, thereby rendering the muscle liable to fatigue. We examine whether a well-defined ....This grant investigates the regulation of an enzyme in skeletal muscle referred to as the sodium-potassium pump, since its function is to pump potassium into the cell and sodium out of the cell. This enzyme is vital in enabling the muscles to contract and plays a key role in supporting our capacity to exercise. Our studies have suggested that acute exercise depresses the maximal capacity (activity) of this enzyme, thereby rendering the muscle liable to fatigue. We examine whether a well-defined exercise leading to fatigue, does inhibit the sodium-potassium pump and whether recovery occurs within 3 hours after exercise. The sodium-potassium pump is comprised of several variations of very similar enzymes, known as isoforms, each under the control of a separate gene and having slightly different functions and regulation. We explore whether exercise causes the genes regulating these isoforms to be activated and whether this results in an increased isoform formation in the muscle cell. We use a drug commonly used in patients with heart failure, called digoxin, which blocks the action of the sodium-potassium pump. In rat muscles this reduces muscular performance, with earlier and more pronounced fatigue. We examine whether a similar detrimental effect occurs in muscles of exercising humans and measure the resultant effects on muscle sodium and potassium levels. Increased knowledge about the effects of a single exercise bout on muscle is important fundamental knowledge. The study will lead to new knowledge about sodium-potassium pump regulation in exercising humans and thus enhance our understanding of muscle fatigue and gene responses to exercise. Understanding exercise effects will assist in development of strategies to counter physical inactivity, which is a major burden on health in Australia. Improved understanding of the actions of digoxin will also benefit patients with heart failure, through modified drug use and development of more specific treatment.Read moreRead less
Characterisation Of The Molecular Mechanisms Mediating Aldosterone-induced Epithelial Electrolyte Transport
Funder
National Health and Medical Research Council
Funding Amount
$488,386.00
Summary
The steroid hormone aldosterone regulates blood pressure by controlling sodium retention. The importance of this role is underlined by the fact that all known mongenetic hypertensive conditions involve aldosterone or sodium retention. Aldosterone mediates this effect by activating an intracellular receptor protein that in turn switches on specific genes. This study seeks to identify the genes that are switched on (or off) by aldosterone and to characterise the region of the gene that interacts w ....The steroid hormone aldosterone regulates blood pressure by controlling sodium retention. The importance of this role is underlined by the fact that all known mongenetic hypertensive conditions involve aldosterone or sodium retention. Aldosterone mediates this effect by activating an intracellular receptor protein that in turn switches on specific genes. This study seeks to identify the genes that are switched on (or off) by aldosterone and to characterise the region of the gene that interacts with the receptor. Both cell and gene specific factors are thought to be important in defining the nature of this interaction; these factors will also be sought. This information will enhance our understanding of the basic biology of sodium transport in the colon and the kidney which in turn will clarify the role of aldosterone in high blood pressure, cardiac disease and perhaps even stress.Read moreRead less
Fluid intake is essential for survival. Disorders of thirst whether they be excessive or inadequate have dire conseqences as evidenced in recent heat waves in Europe and Indiawhere thousands of lives were lost primarily in the elderly whose thirst mechanisms are often disrupted. The excessive fluid intake, seen in psychotic disorders such as schizophrenia, is equally damaging. Much of the research over the last 50 years has concentrated on the hypothalamic regulation of thirst. This project will ....Fluid intake is essential for survival. Disorders of thirst whether they be excessive or inadequate have dire conseqences as evidenced in recent heat waves in Europe and Indiawhere thousands of lives were lost primarily in the elderly whose thirst mechanisms are often disrupted. The excessive fluid intake, seen in psychotic disorders such as schizophrenia, is equally damaging. Much of the research over the last 50 years has concentrated on the hypothalamic regulation of thirst. This project will attempt, for the first time, to define the location in the cerebral cortex of the drive to ingest water (perception of thirst).Read moreRead less
Extracellular Acidification And Its Role In Disease
Funder
National Health and Medical Research Council
Funding Amount
$371,529.00
Summary
This proposal focuses on the diseases cystic fibrosis and acute pancreatitis for which there are currently no treatments. In both diseases the affected organs become strongly acidic. Furthermore, these acid changes can be causal in disease progression. However, the source of this acidification is remains unknown. We will identify the routes of acid secretion, the causal role of acidification in disease progression and the effectiveness of treatments aimed at restoring acid-base balance.
Multisensory Determinants Of Postural Instability And Falls In Older Adults; Prevention And Rehabilitation
Funder
National Health and Medical Research Council
Funding Amount
$387,489.00
Summary
With an increased longevity of the population, age-related health problems, such as falls, are a significant socioeconomic issue to be addressed. Many sensory systems (e.g. vision, hearing, balance) are known to gradually become disrupted as a consequence of ageing. This project will investigate the consequences of declining sensory systems for balance control in older adults and to develop technology to prevents falls in them.
Neural Circuits Which Limit Alcohol And Soft Drink Intake
Funder
National Health and Medical Research Council
Funding Amount
$523,949.00
Summary
Alcohol and soft drinks are ubiquitous, and often harmful, particularly in excess. This project will examine the specific roles of fluid and food satiation neural circuits in suppressing intake, to determine whether either or both could be therapeutic targets for alcohol/soft drink overconsumption, especially as cessation aids for binge-drinking behaviour.
Restrictive Versus Liberal Fluid Therapy In Major Abdominal Surgery: The RELIEF Trial
Funder
National Health and Medical Research Council
Funding Amount
$2,477,820.00
Summary
Major surgery can result in serious complications, some of which lead to permanent disability and early death. All patients undergoing major surgery require intravenous fluids to maintain a healthy circulation, but too much fluid can cause tissue swelling (oedema) and "drown" the vital organs. There are probable benefits of a restrictive IV fluid regimen. This could have major benefits to patients having surgery.