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
The Cause Of Undescended Testis And Inguinal Hernia
Funder
National Health and Medical Research Council
Funding Amount
$743,848.00
Summary
This study aims to define in both animal models and children how the testis descends from the abdomen to scrotum, and how undescended testis and inguinal hernia are likely to be caused by defects in the same, very indirect signalling pathway. The results will demonstrate where to look for genetic causes and proof of principle for possible future medical treatments for the 3 commonest major operations in children for congenital and acquired undescended testis and inguinal hernia.
I am an orthopaedic surgeon and clinician-scientist based at Sydney’s largest children’s hospital. My goal is to improve treatments for children with traumatic injuries and bone deformity. I have worked in bone research for over 20 years. My current research interests are finding new treatments for drug-resistant bacterial infections, treating genetic bone disease, and developing new medical devices to help children’s bones grow straight.
Nitric Oxide On Cardio Pulmonary Bypass In Congenital Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,878,889.00
Summary
Children undergoing open heart surgery on a heart lung machine can experience serious side effects from the exposure to the artificial circulation during surgery and may have either prolonged need for life support in intensive care or even may suffer from long term complications. In this study we investigate the use of a new approach using nitric oxide, a anti-inflammatory gas, during surgery to reduce these side effects.
Surgical Management Of The Pulmonary Circulation In Children
Funder
National Health and Medical Research Council
Funding Amount
$114,328.00
Summary
Congenital disorders of the lung circulation are rare. These children often present during infancy with symptoms of heart failure and require surgery to correct these defects. Without surgery, the prognosis of these conditions are poor. Our understanding of these conditions are limited. The proposed study aims to review all patients who underwent surgical repair of abnormalities of lung arteries and veins at the Royal Children’s Hospital.
Does Remote Ischemic Preconditioning Induce Protective Mitochondrial Function In Congenital Heart Defect Repair Surgery?
Funder
National Health and Medical Research Council
Funding Amount
$142,759.00
Summary
The body's own protective mechanism against injury due to reduced blood flow (ischemic preconditioning) has been studied for over 2 decades, yet the clinical benefits have not been realised until recently . We have previously shown that this innate protection can be induced without drugs in children having heart surgery. We will extend these findings to determine the mechanism of protection, develop a method to monitor this in blood cells and see if this is related to post-operative outcomes.
Novel Cell Therapy For Hirschsprung Disease: From Patient IPS Cells To Large Animal Trials
Funder
National Health and Medical Research Council
Funding Amount
$1,011,764.00
Summary
In Hirschsprung disease the lower bowel has no nerve cells. It does not function so it is surgically removed but quality of life is poor. A new idea is to replace the missing cells with new ones. Human infants are very large so we will use new stem cell technologies to create large numbers of cells. We will use polymer chemistry to devise a method of getting the cells into such a large organ as the bowel, and trial these on a model, the piglet, which closely resembles in size the human baby.
Health-Related Quality Of Life In Intractable Paediatric Epilepsy: Using A New Measure To Improve Management
Funder
National Health and Medical Research Council
Funding Amount
$252,940.00
Summary
Until recently there was no adequate measure to assess the quality of life of children with epilepsy. Our Australian centre was the first to develop, validate and publish such an instrument; the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE). We now aim to collect more data using the QOLCE to gain further understanding of the effects of epilepsy and its treatment on the quality of life of children. We will determine if surgery in children stops seizures and improves quality of life. ....Until recently there was no adequate measure to assess the quality of life of children with epilepsy. Our Australian centre was the first to develop, validate and publish such an instrument; the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE). We now aim to collect more data using the QOLCE to gain further understanding of the effects of epilepsy and its treatment on the quality of life of children. We will determine if surgery in children stops seizures and improves quality of life. We also aim to find out if children with different types of epilepsies have unique quality of life issues. Finally, we aim to determine if the quality of a child's life depends on how well they are thinking and learning or how often they are having seizures. We will conduct this study in children with difficult epilepsy recruited from three major children's hospitals (Sydney Children's Hospital, the Children's Hospital, Westmead, Miami Children's Hospital, Florida USA) using a well designed methodology. Each child will have their particular type of epilepsy characterised using video and brain wave analysis. Each parent and older child will receive a quality of life package including the QOLCE to assess life function. In addition, all children will have an assessment of their thinking and learning by a child psychologist. At the completion of this project we will have established whether surgical treatment in children with epilepsy stops seizures and improves quality of life. This will allow clinicians and parents to better understand the effects of surgical treatment in this population. In addition, we will determine if problems in quality of life are associated with specific types of epilepsy. This information can be used to counsel families and tailor interventions and treatments. Finally, we will know whether a child's quality of life is determined by problems with thinking and learning and-or seizures.Read moreRead less
A Randomised Control Trial Of Medical Treatment Versus The Placement Of The Lap Band In Severely Obese Adolescents.
Funder
National Health and Medical Research Council
Funding Amount
$481,905.00
Summary
There has been a substantial rise in the number of overweight and obese adolescents in our community. While prevention of obesity is the ultimate goal, effective stratagies for the management of obese adolescents must be sought. Unfortunately there are few studies that have focused on this problem in adolescents and success has been very limited. Modern obesity surgery is the only reliable method of achieving and sustaining major weight loss in severely obese (body mass index > 35 kg-m2) adul ....There has been a substantial rise in the number of overweight and obese adolescents in our community. While prevention of obesity is the ultimate goal, effective stratagies for the management of obese adolescents must be sought. Unfortunately there are few studies that have focused on this problem in adolescents and success has been very limited. Modern obesity surgery is the only reliable method of achieving and sustaining major weight loss in severely obese (body mass index > 35 kg-m2) adults and there are now several small studies that demonstrate its effectiveness in adolescents. Modern obesity surgery involving the keyhole placement of an adjustable band around the very upper part of the stomach has proven to be safe and effective and requires one 24 hr stay in hospital. In this collaborative study, involving the Monash University Centre for Obesity Research and Education and the Royal Children's Hospital, we propose to formally test, for the first time, the effectiveness of a weight loss program that includes adjustable band surgery, and compare this with a comprehensive best care behavioral program, over a period of 2-years in severely obese adolescents. We estimate that suitable subjects will come from the top 1% for body mass index in our community. After thorough assessment 50 suitable candidates with ages ranging from 14 to 18 years will be randomly allocated to one of the two treatment programs. The intensity of each program will be similar. A broad range of measues including: weight, health status, physical disability, psychological status, body image and quality of life, will be performed before and at completion of the 2-year programs. In addition we will compare the complications, compliance and cost of the two programs. This study will help us assess and compare the effectiveness of the 2 programs and provide vital information regarding the role of modern keyhole obesity surgery for the management of severely obese adolescents.Read moreRead less