Factor V Leiden Mutation: A Contributory Factor For Cerebral Palsy?
Funder
National Health and Medical Research Council
Funding Amount
$72,595.00
Summary
Cerebral palsy is the commonest physical disability in childhood. It has a major impact on individuals and families. In a significant proportion of cases, the cause is unknown so further research is essential to define the reasons for this condition, and thereby develop preventative strategies. Two mutations have been identified that predispose carriers to develop blood clots (called thrombosis). These mutations are the Factor V Leiden mutation and the coagulation gene for prothrombin (also know ....Cerebral palsy is the commonest physical disability in childhood. It has a major impact on individuals and families. In a significant proportion of cases, the cause is unknown so further research is essential to define the reasons for this condition, and thereby develop preventative strategies. Two mutations have been identified that predispose carriers to develop blood clots (called thrombosis). These mutations are the Factor V Leiden mutation and the coagulation gene for prothrombin (also known as the G20210A mutation). If blood clots form in, or travel to the brain (embolism), they can obstruct the blood supply causing damage that may result in cerebral palsy in young children. Our research will investigate both mothers of children with cerebral palsy, and the children themselves. The study of the mothers will determine whether those that are carriers of these mutations are at an increased risk of having children with cerebral palsy. Factors that may precipitate the development of blood clots, such as smoking during pregnancy, will be investigated. The children with cerebral palsy will be studied to determine whether they carry the mutations, and if so, whether they have brain scan evidence of previous blood clots. Children will be tested for the mutation using the blood spot taken routinely early in life. These blood spots are stored on cards (Guthrie cards) and are available for research following parental consent. The mothers will be tested for the mutation by using a saliva sample and will also be interviewed to obtain details of their pregnancies. As a result of this project, useful information will be provided for families and health care providers. It will be established whether these mutations play a role in the genesis of cerebral palsy. In addition, data about possible factors which may increase the risk in carrier mothers, such as smoking, will be provided.Read moreRead less
Limiting Tuberculosis Transmission And Improving The Care Of Affected Children
Funder
National Health and Medical Research Council
Funding Amount
$412,419.00
Summary
Tuberculosis (TB) is the biggest infectious disease killer on the planet. Drug-resistant TB poses a particular challenge in the Asia-Pacific region. My research will assist Australia to progress towards domestic TB elimination. It will improve the management of “difficult to treat” cases and help to safeguard the public against ongoing TB transmission. Work in neighbouring countries will help to contain the spread of drug-resistant TB and protect vulnerable young children.
How Do Antibiotics Affect The Gastrointestinal Microbiome In Children?
Funder
National Health and Medical Research Council
Funding Amount
$215,000.00
Summary
Antibiotics, while vital, have potentially long term negative effects on antimicrobial resistance and other aspects of health. Microorganisms living in the human intestine, collectively the gastrointestinal microbiome, are believed to play a key role. Antibiotics can change the microbiome, and this is potentially important in children due to the longevity of health effects. We aim to determine the effect of different antibiotics (broad versus narrow) on the microbiome over time in children.
Metabolic Complications Of Obstructive Sleep Apnea During Early Development
Funder
National Health and Medical Research Council
Funding Amount
$320,375.00
Summary
Adults with OSA are known to have increased risk for heart disease. We will study children with OSA, and an animal model of the disease during early development, to help clarify how this disease of adulthood actually has its origins in childhood. We have already shown that obese children with obstructive sleep apnea (OSA) are more prone to diabetes (metabolic problems) than those without OSA. More recently, we found that this is also true for children who are not overweight. This early diabetes ....Adults with OSA are known to have increased risk for heart disease. We will study children with OSA, and an animal model of the disease during early development, to help clarify how this disease of adulthood actually has its origins in childhood. We have already shown that obese children with obstructive sleep apnea (OSA) are more prone to diabetes (metabolic problems) than those without OSA. More recently, we found that this is also true for children who are not overweight. This early diabetes is known to be to show a future risk for heart disease. This study will examine why OSA in children is linked to metabolic problems. First, we will continue our study in children who are not overweight. We need to study more children to be sure that OSA is truly linked to metabolic problems - whether or not a child is overweight, because this means that children with OSA are at risk for metabolic and future cardiac problems, whether they are overweight or not. Since weight does not usually change after treatment of OSA, we will also study children again, after they have been treated for OSA. We expect to show that treatment of OSA resolves the metabolic problems. Since hypoxia (low oxygen) occurs in OSA we believe that this is the fundamental cause of the metabolic problems. To test whether this is true, we will look for metabolic problems in piglets exposed to similar, low levels of oxygen as those seen in children with OSA, comparing them to piglets that have not been so exposed. We believe that the tendency to develop OSA and diabetes is inherited. To test this, we will study the genes of a very large family whose members have OSA and-or diabetes, and try to find which genes are associated with OSA and with diabetes. This will help determine if the two genes are linked in some way.Read moreRead less
The Role Of Microtubule Composition In The Efficacy Of Antimicrotubule Agents In Paediatric Malignancy
Funder
National Health and Medical Research Council
Funding Amount
$173,380.00
Summary
To enhance the management of both childhood and adult cancers improved understanding of the processes responsible for tumour aggressiveness and drug resistance are required. Microtubules are important structural components of cells which are crucial for normal cell division. This makes microtubules excellent targets for anticancer drugs which can disrupt microtubules and kill cancer cells. This proposal will identify whether the microtubule composition of a tumour cell will predict for the aggre ....To enhance the management of both childhood and adult cancers improved understanding of the processes responsible for tumour aggressiveness and drug resistance are required. Microtubules are important structural components of cells which are crucial for normal cell division. This makes microtubules excellent targets for anticancer drugs which can disrupt microtubules and kill cancer cells. This proposal will identify whether the microtubule composition of a tumour cell will predict for the aggressiveness of certain cancers, and whether this influences which tumours will respond to the vinca alkaloids. The vinca alkaloids are an important class of natural product drugs which disrupt microtubules and are particularly effective in the treatment of adult and childhood cancers. Unfortunately, some cancer cells fail to respond to this treatment due to the development of drug resistance. This proposal addresses vinca alkaloid resistance in children?s cancer and will determine why certain cancer cells fail treatment. Furthermore, this study will identify the role of certain components of microtubules that appear to be related to drug resistance in leukaemia and neuroblastoma cells and whose role is unknown. Chemotherapeutic drugs, such as the vinca alkaloids, are important in the treatment of cancer and knowledge about their interaction with their cellular target will improve the design of new drugs and treatment outcome.Read moreRead less
Family And Environment In The Development Of Obesity And Precursors Of Diabetes And Heart Disease In Adolescence
Funder
National Health and Medical Research Council
Funding Amount
$284,770.00
Summary
Obesity is a serious public health problem in Australia. The rate of obesity appears to be rising. Currently 19-23% of children and adolescents are overweight or obese. Adolescence is a critical period for the development of obesity in both males and females. It is a time when new dietary habits, likely to promote fatness, are adopted and physical activity declines. Understanding the factors that drive these behaviours is essential for effective prevention of obesity and related diseases. In 199 ....Obesity is a serious public health problem in Australia. The rate of obesity appears to be rising. Currently 19-23% of children and adolescents are overweight or obese. Adolescence is a critical period for the development of obesity in both males and females. It is a time when new dietary habits, likely to promote fatness, are adopted and physical activity declines. Understanding the factors that drive these behaviours is essential for effective prevention of obesity and related diseases. In 1996-7, our research group studied a group of over 400 children who were aged 7-8 years, were living in western Sydney and were born at Nepean Hospital. In our new study, we plan to re-study this group of children, now in early adolescence. This will allow us to assess the family and environmental factors influencing physical activity and eating behaviour at the beginning of adolescence. The aims of our study are to: Measure changes during early adolescence in eating and physical activity behaviours that are likely to increase obesity risk Measure anthropometric and biochemical markers for future risk of type 2 diabetes and cardiovascular disease in both adolescents and their parents Identify factors in the family environment that influence changes in food intake and physical activity in early adolescence The study will be done in two phases, 18 months apart. The measurements will be done in the study centre at Nepean Hospital in western Sydney. We will measure the height, weight and skinfold thickness of the adolescents and, if possible, their parents. We will also ask the young people and their parents to complete questionnaires about the family food and activity environment and their level of physical activity and food intake. In addition, the adolescents will wear a light-weight activity monitor for 3 days ( to measure the level of activity), blood pressure will be measured and cholesterol and blood sugar levels checked.Read moreRead less
Metformin In Gestational Diabetes: Follow-up Of Mothers And Offspring: Body Composition, Insulin Resistance, Development
Funder
National Health and Medical Research Council
Funding Amount
$630,142.00
Summary
Children born to women with gestational diabetes are at increased risk of later obesity and diabetes. This study will help to assess if giving such women during their pregnancy the cheap oral diabetes drug metformin rather than insulin injections can safely reduce this risk, measuring growth, fatness and blood glucose-insulin in the children at 2 and 5 years of age, as well as assessing the mothers. If so, such treatment might help to reduce the worldwide burden of disease related to obesity.