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
Which Oxygen Saturation Level Should We Use For Very Premature Infants? A Randomised Controlled Trial.
Funder
National Health and Medical Research Council
Funding Amount
$2,215,600.00
Summary
Retinopathy of prematurity (ROP) is a serious complication of premature birth, and is a major cause of preventable blindness. Babies who are born before 28 weeks gestation are at greatest risk for developing severe ROP. Oxygen is one of the most common therapies used daily to care for premature babies, but high oxygen levels are one of multiple factors that can disrupt normal eye development and contribute to ROP. The current dilemma is that doctors and nurses do not know what level of oxygenati ....Retinopathy of prematurity (ROP) is a serious complication of premature birth, and is a major cause of preventable blindness. Babies who are born before 28 weeks gestation are at greatest risk for developing severe ROP. Oxygen is one of the most common therapies used daily to care for premature babies, but high oxygen levels are one of multiple factors that can disrupt normal eye development and contribute to ROP. The current dilemma is that doctors and nurses do not know what level of oxygenation is both safe and most effective for these babies. Whilst higher oxygen levels may increase ROP and other respiratory problems, it is possible that lower oxygen levels may affect other long-term outcomes. Because there is no definitive evidence regarding appropriate oxygenation, a wide spectrum of opinion and practice currently exist. Australia is conducting The Benefits of Oxygen Saturation Targeting Trial (BOOST II), a research study to solve this dilemma. BOOST II is a randomised, double blind, clinical trial, which will study the effects of using two ranges of oxygen saturation, 85-89% versus a higher range 91-95% for infants born before 28 weeks gestation. Both of these oxygen level ranges are currently used in normal practice. Patient safety will be monitored closely, and each infant will have their development, vision and health assessed by specialists at 18-24 months of age (plus the number of weeks premature), to see whether there is difference in survival free of major disability between the two groups. 1200 Australian infants will participate. This study will answer important questions about the benefits and risks of higher versus lower oxygen levels, and will improve the care of thousands of Australian children and millions more worldwide.Read moreRead less
Improving The Efficacy Of Retinoid Therapy In Childhood Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$295,336.00
Summary
Cancer is still the commonest disease causing death in chilhood. Childhood neuroblastoma is a cancer of the nerve tissue which presents usually as a widely spread malignancy, which responds poorly to conventional therapy, indicating the need for novel treatment approaches. Vitamin A derivatives, or retinoids, given in addition to conventional therapy improves the cure rate for children with advanced neuroblastoma to 50%. We have shown that one likely mechanism of retinoid resistance is a deficie ....Cancer is still the commonest disease causing death in chilhood. Childhood neuroblastoma is a cancer of the nerve tissue which presents usually as a widely spread malignancy, which responds poorly to conventional therapy, indicating the need for novel treatment approaches. Vitamin A derivatives, or retinoids, given in addition to conventional therapy improves the cure rate for children with advanced neuroblastoma to 50%. We have shown that one likely mechanism of retinoid resistance is a deficiency of retinoic acid receptor beta, which is a necessary factor in the neuroblastoma cell for converting the retinoid anti-cancer signal into an irreversible cellular change. In this project we will define why some neuroblastoma cells express low levels of this protein and test new retinoid therapies.Read moreRead less
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
The aim of this proposal is to evaluate a novel therapy option for children with a genetic disorder called mucopolysaccharidosis (MPS). MPS arise from the build up of complex carbohydrates in cells within the body due to the deficiency of an enzyme required for their degradation. By decreasing the synthesis of carbohydrate we can manipulate the level of stored carbohydrate and alleviate the pathology associated with MPS. The novel therapy is based on a chemical modification of glucose that inhib ....The aim of this proposal is to evaluate a novel therapy option for children with a genetic disorder called mucopolysaccharidosis (MPS). MPS arise from the build up of complex carbohydrates in cells within the body due to the deficiency of an enzyme required for their degradation. By decreasing the synthesis of carbohydrate we can manipulate the level of stored carbohydrate and alleviate the pathology associated with MPS. The novel therapy is based on a chemical modification of glucose that inhibits carbohydrate synthesis and is termed substrate deprivation therapy.Read moreRead less
A Randomised Trial Of Constraint Induced Movement Therapy And Botulinum Toxin A In Children With Congenital Hemiplegia.
Funder
National Health and Medical Research Council
Funding Amount
$399,995.00
Summary
Congenital hemiplegia occurs in over 1 million children under 21 years of age in the industrialized world. It is the most common type of cerebral palsy, accounting for 36 percent of children diagnosed with this lifelong condition. We intend to determine if a promising new treatment approach is effective in providing a superior and lasting benefit, compared to conventional techniques. Children with hemiplegia usually have the intellectual capacity to attend normal school; however the impaired arm ....Congenital hemiplegia occurs in over 1 million children under 21 years of age in the industrialized world. It is the most common type of cerebral palsy, accounting for 36 percent of children diagnosed with this lifelong condition. We intend to determine if a promising new treatment approach is effective in providing a superior and lasting benefit, compared to conventional techniques. Children with hemiplegia usually have the intellectual capacity to attend normal school; however the impaired arm reduces independence in activities of daily living and can compromise their ability to participate in educational, leisure and vocational roles. Previously we have shown that a program of upper limb rehabilitation in children with spasticity was effective in improving participation and quality of life. We have also shown that rehabilitation combined with Botulinum toxin A (Botox) can further improve functional activity. We believe that a new method of therapy, that has been used effectively in Adults with stroke, called Constraint Induced Movement Therapy (CIMT) may also be beneficial in the treatment of children with congenital hemiplegia. In CIMT, the unimpaired arm is constrained in a glove to promote use of the impaired arm (hemiplegic arm). We predict that, combined with the Botox treatment, CIMT will provide a superior and longer lasting benefit compared to standard rehabilitation combined with Botox. The primary aim of our study is to test this hypothesis in a controlled trial. A secondary aim is to further our understanding of the central neurovascular mechanisms underlying changes in upper limb function. To achieve this, we will use Functional Magnetic Resonance Imaging (fMRI) and Transcranial Magnetic Stimulation (TMS) to measure central activation in the parts of the brain controlling movement. Improving our understanding of the mechanisms involved in this condition is an essential next step towards providing a more effective and long lasting treatment.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
School-Age Outcomes Of Very Preterm Infants And Antenatal Magnesium Sulphate Therapy - A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$675,050.00
Summary
Despite recent major advances in care around the time of birth that have led to large increases in the survival rates for very preterm babies, the rate of adverse long-term health problems has not diminished in survivors, and remains too high compared with children not born very preterm. In particular they have higher rates of substantial problems with the way their brain works, particularly affecting their movement, vision, hearing, thinking and talking. We have just concluded a large clinical ....Despite recent major advances in care around the time of birth that have led to large increases in the survival rates for very preterm babies, the rate of adverse long-term health problems has not diminished in survivors, and remains too high compared with children not born very preterm. In particular they have higher rates of substantial problems with the way their brain works, particularly affecting their movement, vision, hearing, thinking and talking. We have just concluded a large clinical trial in Australia and New Zealand of magnesium sulphate which was given to mothers who were likely to deliver their baby too early (before 30 weeks of pregnancy). We have been able to show, for the first time, that magnesium sulphate was able to halve the rate of substantial problems with movement in 2 year old survivors, from 6% to 3%. However, we are not sure if this potentially important improvement will translate into better outcomes for the children as they grow older and reach school-age. As there are many examples of treatments given around the time of birth that have been shown to have some short-term benefits, but substantial long-term harms, we must be as certain as we can be that any advance in one small area of health is not counterbalanced by disadvantages in other health areas. We plan to assess the 1061 survivors from our earlier clinical trial of magnesium sulphate therapy at ages from 7-8 years, when they are at school. We will assess their movement and other important areas of their brain function, as well as their school progress and general health and growth. If we find important improvements in health at school-age of these children caused by magnesium sulphate therapy, without any substantial counterbalancing side-effects, magnesium sulphate will probably become standard therapy in mothers who are likely to deliver their baby very early. This will lead to a reduction in the burden of illness in the community caused by being born too early.Read moreRead less