Sensory Innervation Of The Anal Region In Normal And Diabetic Guinea Pigs
Funder
National Health and Medical Research Council
Funding Amount
$372,389.00
Summary
Until something goes wrong, we take it for granted that we can empty our bowels on a regular basis, at a time and place of our choosing. Failure to achieve this is very distressing and substantially diminishes quality of life, if it occurs regularly. Disordered defecation, fecal incontinence and constipation are surprisingly common and their prevalence will continue to increase as our population ages and the incidence of diseases such as diabetes increases. In many people suffering these problem ....Until something goes wrong, we take it for granted that we can empty our bowels on a regular basis, at a time and place of our choosing. Failure to achieve this is very distressing and substantially diminishes quality of life, if it occurs regularly. Disordered defecation, fecal incontinence and constipation are surprisingly common and their prevalence will continue to increase as our population ages and the incidence of diseases such as diabetes increases. In many people suffering these problems, there is a detectable dysfunction of the sensory nerves in the anal region. These nerves supply information from the anal region to the spinal cord that can cause us to sense activity in our lower bowel and initiate defecation reflexes. These sensory pathways are important for clinical gastroenterology, but remarkably little is known about them. We are now able to investigate what it is the sensory nerves in the anal region sense, what they look like and where they go to in the spinal cord - in a single project. To do this we will use simple, but novel techniques that have been developed in this laboratory in an animal model. Once we know this, we will compare the function of sensory nerves in the anal region in diabetic animals with normal animals. This will give us insight into the role of sensory nerves in the development of fecal incontinence an unpleasant symptom for many people suffering advanced diabetes. My systematic approach will provide understanding of the basic cellular mechanisms and nerve pathways that underlie sensation in the anal region, helping both clinicians and patients understand the cause of defecatory disorders and potentially pointing the way to new therapies and strategies for diagnosis.Read moreRead less
Alternatives To Polysomnography For Children With Suspected Obstructive Sleep Apnoea.
Funder
National Health and Medical Research Council
Funding Amount
$357,613.00
Summary
Snoring is the cardinal symptom of obstructive sleep apnoea (OSA), a major health issue in childhood with significant impacts on cognition, behaviour and cardiovascular health. Approximately 35% of children snore but only about 10% of those have OSA. Defining OSA in a snoring child requires polysomnography, a technically challenging and expensive test. In this study we will examine a number of simple tests for their predictive power for OSA, developing a tool that will enable clinicians to diagn ....Snoring is the cardinal symptom of obstructive sleep apnoea (OSA), a major health issue in childhood with significant impacts on cognition, behaviour and cardiovascular health. Approximately 35% of children snore but only about 10% of those have OSA. Defining OSA in a snoring child requires polysomnography, a technically challenging and expensive test. In this study we will examine a number of simple tests for their predictive power for OSA, developing a tool that will enable clinicians to diagnose OSA without the need for polysomnography.Read moreRead less
A Randomised Controlled Trial Of The Effect Of Substantial Weight Loss On Obstructive Sleep Apnoea.
Funder
National Health and Medical Research Council
Funding Amount
$404,061.00
Summary
Obstructive sleep apnea is now commonly recognized as a major health problem and frequently ocurrs in overweight or obese individuals. Several studies have now demonstrated that weight loss can be an effective treatment for sleep apnea in those with a weight problem. But, it is extremely difficult to achieve and sustain the major weight loss required to adequately treat this condition. Modern obesity surgery is the only reliable method of achieving and sustaining major weight loss in very obese ....Obstructive sleep apnea is now commonly recognized as a major health problem and frequently ocurrs in overweight or obese individuals. Several studies have now demonstrated that weight loss can be an effective treatment for sleep apnea in those with a weight problem. But, it is extremely difficult to achieve and sustain the major weight loss required to adequately treat this condition. Modern obesity surgery is the only reliable method of achieving and sustaining major weight loss in very obese individuals, and several studies have found that along with weight loss there are major improvements in sleep symptoms, and sleep apnea following weight loss surgery. Despite these findings surgery is rarely advised and has never been formally tested as a therapy for sleep apnea. We propose to formally test, for the first time, the effectiveness of weight loss surgery, as an addition to best conventional therapy, in those individuals with the combination of problems; obesity and significant sleep apnea. We propose that significant weight loss, following surgery, may indeed be the best therapy for those with these combined problems, and that weight loss may have additional benefits for other common problems related to obesity, including high blood pressure, poor body image and impaired quality of life. Forty appropriate patients who suffer these combined problems will be randomly allocated to either conventional therapy for their sleep apnea and weight problems or to a similar program that includes placement of a Lap-Band, a minimially invasive form of obesity surgery. We will follow the patients for 2-years and serially measure a broad range of health and quality of life outcomes and compare the effects of each program. This study will help us assess the role of obesity surgery in this group of patients with major health problems.Read moreRead less
The Role Of Sleep And Cardiorespiratory Control In The Pathogenesis Of Pre-eclampsia
Funder
National Health and Medical Research Council
Funding Amount
$235,095.00
Summary
Pre-eclampsia occurs in 7-10 % of the pregnant population. This makes it one of the most common diseases associated with pregnancy in the Western world. The cause of pre-eclampsia remains elusive, however, recent research suggests that the initiating factor is abnormal implantation of the placenta into the uterus. This in turn leads to poor flow of blood through the placenta (known as placental ischaemia) resulting in release of mediators (including substances known as cytokines) into the matern ....Pre-eclampsia occurs in 7-10 % of the pregnant population. This makes it one of the most common diseases associated with pregnancy in the Western world. The cause of pre-eclampsia remains elusive, however, recent research suggests that the initiating factor is abnormal implantation of the placenta into the uterus. This in turn leads to poor flow of blood through the placenta (known as placental ischaemia) resulting in release of mediators (including substances known as cytokines) into the maternal circulation which cause widespread damage to the endothelium (the protective layer of cells which line all of the blood vessels throughout the circulation). Furthermore, the greater the demand on the placenta, the more of these toxic substances will be released into the maternal circulation. During sleep, a large proportion of pregnant women snore and consequently have partial reduction in the volume of each breath. In women with healthy placental function, this is not a concern. However, we suggest that in women with pre-eclampsia, this results in further disruption to the blood flow through the placenta, which leads to a greater output of toxic substances from the placenta. We have shown that by controlling snoring during pregnancy in women with pre-eclampsia with the use of nasal continuous positive airway pressure (nasal CPAP), we are able to markedly reduce blood pressure over the night. In this project, we would like to investigate changes occurring during sleep in cytokines in the maternal circulation, and in maternal blood pressure both on and off nasal CPAP in order to establish whether a mechanism during sleep is contributing to the disease process of pre-eclampsia. Furthermore, we intend to investigate whether the long term use of nasal CPAP improves the outcome of pre-eclampsia.Read moreRead less
Sleep Disordered Breathing In Pregnancy: Frequency And Impact.
Funder
National Health and Medical Research Council
Funding Amount
$607,034.00
Summary
Sleep disordered breathing (SDB)affects up to 15% of women during pregnancy. There is some evidence that it may have adverse effects on both mother and baby, particularly it may be associated with a 7-8 fold increase risk of developing hypertension during pregnancy. This study aims to measure breathing during sleep in pregnant women to determine its role in pregnancy-related hypertension and diabetes, then treat the SDB to assess its effect on maternal and foetal outcomes.
Does Adenotonsillectomy Change Vascular Function In Children With Sleep Breathing Disorders?
Funder
National Health and Medical Research Council
Funding Amount
$522,105.00
Summary
Sleep breathing disorders affect 10% of all children and when severe, obstruction in the upper airways causes serious deficits in growth, development, brain function and heart health. But even mild snoring (without obstruction) may also cause poor health in the arteries that supply blood to the brain and heart, as well as the smaller arteries in the arms and legs. In both adults and children with conditions like diabetes and obesity, poor blood vessel health has been shown to greatly increase th ....Sleep breathing disorders affect 10% of all children and when severe, obstruction in the upper airways causes serious deficits in growth, development, brain function and heart health. But even mild snoring (without obstruction) may also cause poor health in the arteries that supply blood to the brain and heart, as well as the smaller arteries in the arms and legs. In both adults and children with conditions like diabetes and obesity, poor blood vessel health has been shown to greatly increase the future risk of heart attacks, angina and strokes. Children with severe sleep breathing disorders (such as sleep apnoea syndrome) are currently treated by removal of the tonsils and adenoids, which typically resolves snoring and improves sleep, but it is not yet known whether there are any benefits for blood vessel health. The earliest signs of blood vessel disease in children are abnormal function of the lining of the blood vessels (endothelial dysfunction) and thickening of the lining of blood vessels (intima media thickness). They precede the adult diseases of atherosclerosis - which causes heart attacks and strokes, and diabetic kidney and eye disease. These changes can be measured accurately and non-invasively using ultrasound imaging of arteries in the neck and arm. Our primary aim is to assess whether changes in blood vessel health occur in children with sleep breathing disorders across the range of severity, with a secondary aim to measure any changes in cardiovascular control during both sleep (when snoring occurs). Most importantly, by assessing children before and after surgery, we will be able to see for the first time whether treatment of childhood snoring improves blood vessel health. This study may have major implications for the clinical management of snoring children, who may require treatment at an earlier age to prevent poor blood vessel health and an increased risk of cardiovascular diseases later in life.Read moreRead less
The Influence Of Sleep On The Behaviour Of The Upper Airway Muscles, Genioglossus And Tensor Palatini
Funder
National Health and Medical Research Council
Funding Amount
$295,880.00
Summary
The human airway has limited bone or cartilage support and muscular activity is required to keep the airway open. Central activation of these muscles is reduced during sleep, resulting in the disorder Obstructive Sleep Apnoea. Potential treatments include pharmocological or electrical stimulation of upper airway muscles. However, this is hampered by a lack of understanding of the control of upper airway muscles. This project will study two critical muscles, genioglossus and tensor palatini.
DOES TREATMENT REVERSE THE NEUROCOGNITIVE AND CARDIOVASCULAR SEQUELAE OF SLEEP DISORDERED BREATHING IN CHILDREN?
Funder
National Health and Medical Research Council
Funding Amount
$519,826.00
Summary
Studies in children have shown that disruption to normal sleep patterns resulting from sleep disordered breathing (SDB) has severe consequences for both the cardiovascular system and neurocognition. To date there have been no studies in children to investigate whether treatment of SDB with adenotonsillectomy, which has been shown to reduce sleep fragmentation and neurocognition, also reduces blood pressure.
Structure And Interactions Of A Disordered Malaria Surface Protein: Implications For Antigenicity
Funder
National Health and Medical Research Council
Funding Amount
$511,020.00
Summary
Malaria is responsible for around 2 million deaths annually, many in children under 5 years of age. Merozoite surface protein 2 (MSP2) from Plasmodium falciparum is being developed as a vaccine candidate. We will investigate the structure of MSP2 in various environments, including when bound to inhibitory antibodies. Key goals are to understand how the disordered structure of MSP2 affects its interaction with the host immune system and how that information can be used to design better vaccines.