A Study To Determine The Effects Of Heparin/ Low Molecular Weight Heparin In Neonates And Children.
Funder
National Health and Medical Research Council
Funding Amount
$193,000.00
Summary
Blood clots in newborns and children are becoming a more common problem. This is because many children with major illnesses are now surviving due to the remarkable advances in medical and surgical care. Blood clots in children can have devastating long term effects. Little is known about the best way to treat blood clots in children and most treatments are just extrapolated from adult treatment guidelines. This is unlikely to be the best treatment as the type and place of blood clots in children ....Blood clots in newborns and children are becoming a more common problem. This is because many children with major illnesses are now surviving due to the remarkable advances in medical and surgical care. Blood clots in children can have devastating long term effects. Little is known about the best way to treat blood clots in children and most treatments are just extrapolated from adult treatment guidelines. This is unlikely to be the best treatment as the type and place of blood clots in children are very different to adults. In addition, the blood clotting system in children is very different to that in adults. This is especially true for newborns. Over the last four years we have established the largest clinical treatment program for children with blood clots in Australia, and have completed the preliminary work that will enable us to now study a number of aspects of the treatment for blood clots in children. This project will specifically examine heparin and low molecular weight heparin which are the most commonly used antithrombotic (anti blood clot) drugs in children. We will determine the effect of age on the mechanism of action, the optimal drug level for treatment, the frequency of the most common side effect of heparin and do some preliminary work to determine alternative treatment options. Our study will provide the basis for more appropriate use of these drugs in children, which will improve the success of therapy and reduce the risk of complications, ultimately improving the survival and quality of life for sick children affected by blood clots.Read moreRead less
A Randomised Controlled Trial Of A Fluid Containing 140mmol/L Of Sodium Compared To A Fluid Containing 77mmol/L Of Sodium For Maintenance Intravenous Fluid Therapy In Hospitalised Children.
Funder
National Health and Medical Research Council
Funding Amount
$183,959.00
Summary
Intravenous fluid therapy is one of the most common and important treatments for children in hospital. In spite of this we know very little about what fluid should be used and there is now good evidence that children are experiencing adverse outcomes because of fluid treatment. The aim of this trial is to determine which intravenous fluid is best in children. It will be the largest and most relevant intravenous fluid trial performed in children. The results will have an immediate impact on treat ....Intravenous fluid therapy is one of the most common and important treatments for children in hospital. In spite of this we know very little about what fluid should be used and there is now good evidence that children are experiencing adverse outcomes because of fluid treatment. The aim of this trial is to determine which intravenous fluid is best in children. It will be the largest and most relevant intravenous fluid trial performed in children. The results will have an immediate impact on treating children worldwide.Read moreRead less
Transcriptional Regulation Of The Tumour Suppressor Gene, Retinoic Acid Receptor Beta
Funder
National Health and Medical Research Council
Funding Amount
$336,540.00
Summary
Cancer is still the second commonest cause of death in children. Neuroblastoma is the commonest solid tumour under the age of five years. Neuroblastoma responds poorly to conventional chemotherapy, unlike many other childhood cancers, and thus represents a major unsolved child health problem. A major advance in the field was a recent trial in th US demonstrating that treatment with oral vitamin A improved survival rates in children with advanced neuroblastoma. In previous studies we have identif ....Cancer is still the second commonest cause of death in children. Neuroblastoma is the commonest solid tumour under the age of five years. Neuroblastoma responds poorly to conventional chemotherapy, unlike many other childhood cancers, and thus represents a major unsolved child health problem. A major advance in the field was a recent trial in th US demonstrating that treatment with oral vitamin A improved survival rates in children with advanced neuroblastoma. In previous studies we have identified that a particular gene retinoic acid receptor beta, known to be involved in the vitamin A anticancer effect may be deficient in some neuroblastoma tumours, and is vital to the anticancer effect of vitamin A in neuroblastoma cells. In this application we hope to define those cellular factors which are necessary for turning on the expression of this gene.Read moreRead less
A Prospective Randomised Trial Comparing Nasogastric With Intravenous Hydration In Children With Bronchiolitis
Funder
National Health and Medical Research Council
Funding Amount
$886,817.00
Summary
This project aims to compare the two methods currently being used of providing fluid to young children who have a viral infection of the lungs called bronchiolitis. The methods of giving fluids are through a tube placed though the nose, down the food pipe, into the stomach (nasogastric tube), or through a drip in the child's vein (intravenous). We hope to show that one of these methods is better than the other and allows children to be sent home from hospital earlier, and cost less.
Cancer is still a major cause of mortality in adults and children. Several lines of evidence suggest that some childhood cancers may arise due to factors, which interfere with the normal process of early development in embryonal tissues. The nature of the molecular factors which derail normal embryogenesis, their mechanism and timing, is vital information for efforts to generate novel pharmaceuticals. Moreover, factors which are necessary for tumour initiation, might be very good targets for a c ....Cancer is still a major cause of mortality in adults and children. Several lines of evidence suggest that some childhood cancers may arise due to factors, which interfere with the normal process of early development in embryonal tissues. The nature of the molecular factors which derail normal embryogenesis, their mechanism and timing, is vital information for efforts to generate novel pharmaceuticals. Moreover, factors which are necessary for tumour initiation, might be very good targets for a cancer prevention strategy. If entirely successful, our experiments will show that the MYCN oncoprotein is a key factor in the very earliest stages of neuroblastoma tumour formation, we will define the mechanism of the MYCN effect on the normal process of neural crest development, and, we will provide a basis for future cancer prevention strategies in children with this disease.Read moreRead less
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
The Effect Of Adenotonsillectomy On Neurocognitive Functioning In Children With Upper Airway Obstruction
Funder
National Health and Medical Research Council
Funding Amount
$185,850.00
Summary
Upper airway obstruction during sleep affects up to 3% of all children and is very frequently unrecognised. If severe it causes growth failure, developmental delay and heart failure. However, there is little information on the effects of less severe degrees of upper airway obstruction in children but recent work suggests that reduced academic performance may also be present in children with relatively mild degrees of upper airway obstruction. In particular, the areas most affected appear to be i ....Upper airway obstruction during sleep affects up to 3% of all children and is very frequently unrecognised. If severe it causes growth failure, developmental delay and heart failure. However, there is little information on the effects of less severe degrees of upper airway obstruction in children but recent work suggests that reduced academic performance may also be present in children with relatively mild degrees of upper airway obstruction. In particular, the areas most affected appear to be intelligence, memory, behaviour and attentional capacity . Currently it is unclear whether these deficits are due to sleep disruption or reduced nocturnal oxygen levels. The treatment of upper airway obstruction is the removal of adenoids and tonsils, however, it is unknown whether or not this improves the child's intellectual capacity. This study aims to be one of the first to critically evaluate the impact of upper airway obstruction during sleep on children's intelligence, memory, behaviour and attentional capacity, and the improvements wrought by the removal of the child's tonsils and adenoids.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
Therapy For CNS Degeneration In MPS Disorders That Targets Both Glycosaminoglycan And Ganglioside Storage.
Funder
National Health and Medical Research Council
Funding Amount
$368,043.00
Summary
Children with seven of the eleven types of mucopolysaccharidosis (MPS) disorders exhibit a profound, irreversible neurological deterioration that manifests in infancy. This results from the continual buildup of undegraded sugar and fat in brain cells. The goal of this proposal is to prevent the accumulation of lipid alone or both lipid and sugar in the brain in order to alter the progression of neurological disease. Treatment will be assessed in mouse models of MPS.
Newborn babies are at risk of becoming short of oxygen during delivery. Death or brain damage may result. In the days after birth, when the brain is attempting to recover from the lack of oxygen, seizures (also called fits) are common. Seizures may cause further damage to the brain because they release damaging chemicals such as glutamate or because they make extra energy demands on the brain that cannot be met. It is difficult to be certain whether unusual movements or twitches are seizures or ....Newborn babies are at risk of becoming short of oxygen during delivery. Death or brain damage may result. In the days after birth, when the brain is attempting to recover from the lack of oxygen, seizures (also called fits) are common. Seizures may cause further damage to the brain because they release damaging chemicals such as glutamate or because they make extra energy demands on the brain that cannot be met. It is difficult to be certain whether unusual movements or twitches are seizures or not. To detect seizures, it is necessary to measure the EEG, the tiny electrical signals from the brain that can be measured from the scalp using small stick on electrodes. It is difficult to measure EEG, particularly for longer periods, because the electrodes may fall off, the baby may move excessively or electrical interference may ruin the recording. We are proposing to measure EEG for 48 hours in babies who have suffered a lack of oxygen during delivery. We will develop, optimise and implement a new method of automatically detecting seizures, building upon 6 years of fundamental signal processing research work that we have done in the newborn. We will test this system against the 'gold standard' to determine how accurate it will be in detecting seizures. We will also try to find out whether damage in particular areas of the brain or in particular cell types within the brain is most likely to be associated with seizures. The anticipated outcome is that we will be able to accurately identify seizures. This is a major step on the path to being able to prevent injury to the brain and to monitor the effectiveness of new experimental treatments.Read moreRead less