Hepatic Fibrogenesis In Paediatric Cholestatic Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$254,250.00
Summary
Liver disease in children causes a significant impact on lifespan and quality of life. The commonest causes of liver disease in children are cholestatic, or diseases related to obstruction of bile flow out of the liver. In ways we are only beginning to understand, obstruction of bile flow stimulates liver scar formation which, if untreated, leads to replacement of normal liver tissue and ultimately to failure of the liver. In infants, the most common and serious cholestatic liver disease is bili ....Liver disease in children causes a significant impact on lifespan and quality of life. The commonest causes of liver disease in children are cholestatic, or diseases related to obstruction of bile flow out of the liver. In ways we are only beginning to understand, obstruction of bile flow stimulates liver scar formation which, if untreated, leads to replacement of normal liver tissue and ultimately to failure of the liver. In infants, the most common and serious cholestatic liver disease is biliary atresia. It develops at, or shortly after birth with progressive destruction of the bile ducts, responsible for transporting bile out of the liver. Without early diagnosis and surgery these infants develop progressive liver scarring leading to liver failure and death or liver transplantation within 1-2 years. It is the commonest reason for liver transplantation in children (55-60%) in the Western world. Even with successful surgery, most, if not all patients will come to liver transplantation over the subsequent 25 years because of ongoing, but slower, scar formation. In older children, diseases like cystic fibrosis cause bile duct blockages leading to progressive liver scarring that is slower and unpredictable, contributing to ill health in up to 20% of patients and death from end stage liver disease or liver transplantation in 5%. Using liver tissue from children with these two disorders we have been able to identify the key cells that control the liver scar process, the Hepatic Stellate Cell. We now need to investigate the role of bile constituents on the scar-forming process in these two diseases. We will utilise a well characterised animal model to investigate the influence of bile constituents on cells isolated from this model and apply these findings back to patient samples to determine their role in paediatric cholestatic liver disease. This will help us to better understand the disease process and importantly, develop more effective and earlier treatment.Read moreRead less
In What Position Should We Be Sleeping Preterm Infants In The NICU?
Funder
National Health and Medical Research Council
Funding Amount
$409,742.00
Summary
Preterm babies are at risk of brain injury caused by low cerebral blood flow and oxygenation. The prone sleeping position (lying on abdomen) has been found to decrease both cerebral oxygenation and blood pressure in healthy term babies, and is a major risk factor for Sudden Infant Death Syndrome. However, it is common practice for preterm babies to be slept in the prone position.This study will examine the effects of prone vs supine positions on brain oxygenation in the preterm babies.
Neuro-protection In The Preterm Brain - A New Role For Dopamine Therapy?
Funder
National Health and Medical Research Council
Funding Amount
$183,975.00
Summary
Brain injury in premature babies leads to long term adverse outcome. Preliminary data show that dopamine improves brain oxygen. Our study will define effects of dopamine in preventing injury in the immature brain, using animal studies. In immature lambs receiving dopamine, we will test the protective effect of dopamine on brain oxygenation during hypoxia. Outcome will be measured by examining cell injury on lamb brain slices.
A Pre-clinical Trial Of Early Blood Transfusion For Improving Cerebral Oxygen Delivery In Very Preterm Neonates
Funder
National Health and Medical Research Council
Funding Amount
$970,603.00
Summary
Long-term disability is common in babies born prematurely. This may be due to insufficient delivery of oxygen to the brain, but currently there is no treatment that increases oxygen delivery to the brain. We will determine if blood transfusion is more effective than current treatments given to prevent brain injury in preterm babies. Transfusion has two benefits. It will increase the amount of blood going to the brain. It will also increase the amount of oxygen carried by the blood.
Novel Approaches To Assessing Cerebral Circulation And Oxygenation In Preterm Human Infants.
Funder
National Health and Medical Research Council
Funding Amount
$489,145.00
Summary
In the first few days after birth, some premature babies develop low blood pressure. It is thought that this meant that the amount of blood and oxygen going to the brain would also fall. If blood pressure became very low, this could injure the brain. Drugs are used to prevent low blood pressure, but their effect on blood flow and oxygen in the brain is uncertain. This study aims to develop simple cotside monitoring procedures that allow neonatologists to monitor oxygen supply and blood flow in t ....In the first few days after birth, some premature babies develop low blood pressure. It is thought that this meant that the amount of blood and oxygen going to the brain would also fall. If blood pressure became very low, this could injure the brain. Drugs are used to prevent low blood pressure, but their effect on blood flow and oxygen in the brain is uncertain. This study aims to develop simple cotside monitoring procedures that allow neonatologists to monitor oxygen supply and blood flow in the brain in tiny babies who weigh less than 1000gm, and what happens within the brain when drugs are given to raise blood pressure. We will employ a new instrument that generates low intensity near infrared light which passes safely into the brain and is absorbed according to the amount of oxygen present in very small blood vessels. As the methodology is new, we intend to first validate the measurement in immature lambs. The instrument will then be applied in studies of babies undergoing intensive care and at risk for low pressure and brain injury, as many as 5000 babies each year in Australia.Read moreRead less