Reducing Morbidities In Preterm Growth Restricted Neonates.
Funder
National Health and Medical Research Council
Funding Amount
$687,214.00
Summary
Intrauterine growth restriction (IUGR) is a serious complication of pregnancy and occurs when fetal growth is abnormal, resulting in a fetus that is smaller than it should be for its given gestational age. IUGR babies are at much greater risk of many short and long-term adverse outcomes. This study investigates the role that adverse cardiovascular development plays in the progression of lung, heart and brain disease in preterm IUGR newborns.
Does Maladaptive Remodelling Of The Heart And Vasculature In Response To Preterm Birth Lead To Long-term Cardiovascular Risk?
Funder
National Health and Medical Research Council
Funding Amount
$535,086.00
Summary
Being born prematurely is linked to the development of high blood pressure (a major risk factor for cardiovascular disease) later in life. In this project we will examine whether injury to the cells lining the cardiovascular system and/or structural changes in the wall of the arteries and the heart, as a result of being born early, lead to an elevation in blood pressure and heart dysfunction in adulthood.
Understanding The Causes Of Childhood Congenital Anomalies Of The Kidney And Urinary Tract
Funder
National Health and Medical Research Council
Funding Amount
$609,748.00
Summary
Congenital anomalies of the kidney and urinary tract (CAKUT) is a common cause of renal failure in children. The majority of patients with CAKUT do not know the underlying cause of their renal anomalies. In this proposal we will characterise the developmental events that are perturbed in three mouse models of CAKUT and identify the causal gene responsible in each mouse model. We will translate this information to the clinic by screening patients with CAKUT for mutations in these newly identified ....Congenital anomalies of the kidney and urinary tract (CAKUT) is a common cause of renal failure in children. The majority of patients with CAKUT do not know the underlying cause of their renal anomalies. In this proposal we will characterise the developmental events that are perturbed in three mouse models of CAKUT and identify the causal gene responsible in each mouse model. We will translate this information to the clinic by screening patients with CAKUT for mutations in these newly identified genes.Read moreRead less
Being Born Small Is Not Good For The Heart:early Detection Of Cardiovascular Risk
Funder
National Health and Medical Research Council
Funding Amount
$486,757.00
Summary
Intra uterine growth restriction(IUGR) is linked to adult onset of cardiovascular disease. However, little is known about the mechanism(s) which underlie this link or which babies are most at risk. This study aims to assess cardiovascular function in infants and children who were growth restricted. Early identification of cardiovascular dysfunction may aid in new opportunities for monitoring and therapeutic targets to ultimately reduce later onset of cardiovascular morbidity in this population.
Mucopolysaccharidoses (MPS) are a related group of 11 debilitating genetic disorders affecting children. They result from a reduction or total deficiency of an enzyme required for the removal of carbohydrate structures called glycosaminoglycans (gags). Gag degradation occurs inside the cell in specific organelles termed lysosomes and in the absence of the appropriate enzyme, undegraded gag accumulates in the cell. This leads to a range of clinical symptoms and multiple tissue failure. Symptoms c ....Mucopolysaccharidoses (MPS) are a related group of 11 debilitating genetic disorders affecting children. They result from a reduction or total deficiency of an enzyme required for the removal of carbohydrate structures called glycosaminoglycans (gags). Gag degradation occurs inside the cell in specific organelles termed lysosomes and in the absence of the appropriate enzyme, undegraded gag accumulates in the cell. This leads to a range of clinical symptoms and multiple tissue failure. Symptoms common to more than one MPS type include mental deterioration, blindness, abdominal organ enlargement and bone growth problems leading to short stature and bone loss. My laboratory has had a long-term interest in developing treatment for MPS and our research led to the clinical implementation of enzyme replacement therapy (ERT) for MPS VI in 2005. While providing the first effective, multi-tissue treatment for MPS, our research showed that several tissues were not responsive to ERT. These are the brain, cartilage and cornea, thus children on ERT regimens will still suffer from mental retardation, arthritis and blindness. With the goal of treating these particular tissues we have developed a new approach to MPS therapy called substrate deprivation therapy (SDT). Instead of adding back the missing enzyme, SDT acts by decreasing gag production which in turn reduces the level of accumulated gag in cells. SDT results in the correction of MPS cells in culture and reduces several key clinical symptoms in the mouse model of MPS IIIA. In this proposal we will extend our research to evaluate the effect of SDT on brain and bone-joint pathology. Evaluation of efficacy will take place in the MPS VII mouse which exhibits both brain and bone disease and in a new model of MPS IVA developed specifically for this study which exhibits a joint pathology unique amongst the MPS disorders.Read moreRead less
I am a perinatal paediatrician undertaking clinically-focussed research on brain development, brain disorders, brain therapies, neurodevelopmental outcomes and the development, application and evaluation of new technology to clinical problems.
The Effect Of Very Premature Birth On Brain Development
Funder
National Health and Medical Research Council
Funding Amount
$517,975.00
Summary
The neurological outcome of the premature infant is of major importance. Approximately 2,600 premature infants weighing less than 1500 grams are born annually in Australasia. Of the approximate 2,400 survivors between 5-15% will have a more major cerebral palsy, i.e. around 200 children per annum. A greater proportion of 25-50%, i.e., upto 1200 children will have a developmental disability that will adversely affect their school perfomance requiring special assistance or repeating grades. With a ....The neurological outcome of the premature infant is of major importance. Approximately 2,600 premature infants weighing less than 1500 grams are born annually in Australasia. Of the approximate 2,400 survivors between 5-15% will have a more major cerebral palsy, i.e. around 200 children per annum. A greater proportion of 25-50%, i.e., upto 1200 children will have a developmental disability that will adversely affect their school perfomance requiring special assistance or repeating grades. With an increasing number of very prematurely born infants surviving, the absolute number of affected children will continue to rise. Prevention of these disabilities will require an understanding of the cause. The educational and social implications of these high rates of neuro-developmental disability are enormous and the focus of wide international concern. Magnetic Resonance Imaging : It is a major challenge for neonatologists to be able to understand the impact of their therapies and managements on the developing brain. A window into the newborn brain can be seen utilising advanced magnetic resonance imaging techniques in-vivo to investigate these key issues: 1. What is the nature of brain injury in the prematurely born infant? 2. What are the risk factors for brain injury in the prematurely born infant - and are they able to be altered to reduce this risk - e.g. blood pressure management, steroid therapy 3. Is the brain of a prematurely born infant different from that of a full term born infant at TERM equivalent - if so, how is it different? 4. Are there certain postnatal therapies that relate to any alteration in brain structure and chemistry - e.g. postnatal nutrition, modes of ventilation, pharmacological therapies? 5. How does the brain structure relate to function on long term neuro-developmental follow up of our infants at 2 years?Read moreRead less
Impact Of Sleep Disordered Breathing On Cardiovascular, Behavioural And Neurocognitive Function In Preschool Children
Funder
National Health and Medical Research Council
Funding Amount
$425,703.00
Summary
Studies in school age 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 limited investigations of the effects of SDB in pre-school children despite the knowledge that disruptions to breathing during sleep are maximal at this age and the central nervous system which is immature and developing at this time, is most vulnerable to injury.
Cardiovascular, Neurophysiological And Neurocognitive Assessments To Define Sleep Disordered Breathing In Children
Funder
National Health and Medical Research Council
Funding Amount
$324,008.00
Summary
Disruptions to breathing during sleep (snoring), known as sleep disordered breathing occurs in up to 27% of children and forms a continuum of symptoms ranging from mild to severe. It has previously been thought that only severe disruptions to breathing, as occurs in obstructive sleep apnoea (OSA), were of clinical significance requiring intervention, however recent studies have shown that even snoring with no currently used signs of altered blood oxygenation levels or sleep disruption can have a ....Disruptions to breathing during sleep (snoring), known as sleep disordered breathing occurs in up to 27% of children and forms a continuum of symptoms ranging from mild to severe. It has previously been thought that only severe disruptions to breathing, as occurs in obstructive sleep apnoea (OSA), were of clinical significance requiring intervention, however recent studies have shown that even snoring with no currently used signs of altered blood oxygenation levels or sleep disruption can have a significant impact on daytime functioning and school performance. It is also known that cardiovascular disease is a long-term consequence of untreated sleep disordered breathing in adults, however the long-term effects on the cardiovascular system in children are unknown. This study will examine both the neurocognitive and cardiovascular effects of a range of severities of sleep disordered breathing in children and will identify new more sensitive markers of sleep disruption in order to predict neurocognitive dysfunction. In order to address this most important issue, this project will combine the expertise of scientists and clinicians in the fields of paediatric sleep, cardiovascular control and neuropsychological assessment from Monash and Melbourne Universities, and the Monash Medical Centre and Royal Children's Hospital.Read moreRead less