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
Understanding White Matter Injury In Term-born Children With Cerebral Palsy
Funder
National Health and Medical Research Council
Funding Amount
$193,863.00
Summary
The type of brain injury in cerebral palsy varies. In some children the brain develops abnormally in early pregnancy; others have a stroke or suffer from lack of oxygen around the time of birth. Little is known about the group of children born at term who have damage to the brain’s white matter, a pattern more typical of premature birth. This project will explore brain imaging, potential risk factors, and clinical outcomes for these children to identify possible causes and prevention pathways.
International Neonatal Immunotherapy Study (INIS): A Randomised Trial Of Intravenous Immunoglobulin For Neonatal Sepsis
Funder
National Health and Medical Research Council
Funding Amount
$1,151,250.00
Summary
There is promising evidence that treatment of serious infection in babies with a product naturally occuring in blood, intravenous immunoglobulin (IVIG), may reduce deaths by 40% and reduce brain damage in survivors. This would reduce the social, emotional and financial burden of disability on families, health services and society. In financial terms alone, caring for a severely disabled child costs an extra $50,000 per year. However, more evidence is needed before IVIG can be introduced as routi ....There is promising evidence that treatment of serious infection in babies with a product naturally occuring in blood, intravenous immunoglobulin (IVIG), may reduce deaths by 40% and reduce brain damage in survivors. This would reduce the social, emotional and financial burden of disability on families, health services and society. In financial terms alone, caring for a severely disabled child costs an extra $50,000 per year. However, more evidence is needed before IVIG can be introduced as routine treatment for serious infection in the newborn. The International Neonatal Immunotherapy Study (INIS) is a randomised trial to study the potential benefits of IVIG in 5,000 newborn babies in 150 centres world wide. 26 centres are in Australia and New Zealand, whose expected contribution of 1,500 babies will be vital to the success of the study. INIS is supported by the Commonwealth Government and Australian Red Cross Blood Service, who will oversee the supply and distribution of IVIG, and the NHMRC Clinical Trials Centre, who will coordinate the study. Infants will have a detailed specialist assessment at 2 years of age and a parent questionnaire will be completed, to assess their development. An economic evaluation will be performed to estimate the long-term savings to Australian Health Services and families associated with the IVIG therapy. The IVIG product to be used in Australia is Intragam P, manufactured by CSL, who have an unrivalled safety record. CSL has been making IVIG since 1989 and no transmission of HIV or hepatitis viruses has ever been reported. CSL estimate the risk of transmission of these viruses by IVIG is under 1 in 10 million treatments. INIS will provide reliable evidence about IVIG, a treatment with minimum known risk that may benefit thousands of Australian children and millions more worldwide.Read moreRead less
Should Very Premature Babies Receive A Placental Transfusion At Birth? A Randomised Controlled Trial.
Funder
National Health and Medical Research Council
Funding Amount
$2,875,774.00
Summary
Premature babies under 30 weeks gestation are up to a hundred times more likely than full term babies to die or survive with major disability, often from brain damage due to poor blood flow after birth. This randomised study will find out if giving them more placental blood at birth, by means of a delay in clamping the umbilical cord, then milking it, reduces anemia, blood transfusions, brain damage, infection, death and disability. The results may benefit millions of premature babies worldwide.
Mechanisms Contributing To Long-term Neuronal Loss After Hypoxia-ischemia In The Premature Neonate Brain.
Funder
National Health and Medical Research Council
Funding Amount
$432,535.00
Summary
A lack of oxygen (hypoxia) and blood flow to the brain (ischemia) around the time of birth can cause brain injury that perists into adulthood. The burdens on financial, educational and healthcare resources are enormous. We will improve our understanding of what parts of the brain are injured and the mechanisms contributing to on-going brain injury after hypoxia-ischemia.This is important to devise treatments and to provide a healthy start to life for neonates.
A Randomised Controlled Trial Of Whole Body Cooling On The Outcome Of Term Infants With Hypoxic Ischaemic Encephalopathy
Funder
National Health and Medical Research Council
Funding Amount
$386,732.00
Summary
The aim of this project is to investigate whether the brain damage caused by a serious lack of oxygen around the time of birth can be prevented or reduced by cooling the baby's temperature to 34C for 72 hours. The consequences, of a lack of oxygen, to the brain, around the time of birth can be devastating. Over 30% of those babies with abnormal brain function soon after birth either die or survive with severe permanent brain damage. There is no specific treatment for these infants. Evidence from ....The aim of this project is to investigate whether the brain damage caused by a serious lack of oxygen around the time of birth can be prevented or reduced by cooling the baby's temperature to 34C for 72 hours. The consequences, of a lack of oxygen, to the brain, around the time of birth can be devastating. Over 30% of those babies with abnormal brain function soon after birth either die or survive with severe permanent brain damage. There is no specific treatment for these infants. Evidence from studies in animals, as well as human adults and a small number of newborn infants, suggests that moderate body cooling started soon after birth in babies with serious abnormal brain function might prevent or reduce brain damage. This project is a multicentre trial, where infants who have suffered from a severe lack of oxygen around birth, are randomised to body cooling to 34C for 72 hours. This will be started as soon as possible after birth at their hospital of birth. If the baby needs to be transported this will be started when the newborn transport team collects the baby for transfer to a newborn intensive care unit. This new treatment will be compared with maintaining the baby's temperature at 37C. This project will investigate a new, simple and pragmatic treatment that might reduce brain damage. If it finds that cooling infants who have been severely deprived of oxygen is an effective and safe treatment, the information will be applicable to any of the very large number of babies around the world who suffer from a serious lack of oxygen around the time of birth.Read moreRead less