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Does Caffeine Affect The Development Of The Very Immature Brain: Dose Response Relationship?
Funder
National Health and Medical Research Council
Funding Amount
$668,386.00
Summary
Premature birth is a major health problem worldwide. Preterm babies often develop apnoea of prematurity (AOP), which is commonly treated with caffeine. Trials indicate that preterm babies treated with low dose caffeine have less neurodevelopmental disabilities at 18 months. Higher doses of caffeine are often needed to reduce AOP but the risk of this is unknown. We will study the short and long-term effects of increasing doses of caffeine on the developing brain in a long-gestation species.
DEVELOPMENT OF CARDIOVASCULAR CONTROL DURING SLEEP IN HUMAN INFANTS AFTER PRETERM BIRTH
Funder
National Health and Medical Research Council
Funding Amount
$358,537.00
Summary
Infants spend the major part of their life in sleep, and the period between birth and 6 months of age sees dramatic changes in their sleep organisation. Coincidently, there are dramatic developmental changes in the infant's heart and blood pressure control systems, and the ability to compensate for stress such as falls of blood pressure (hypotension) or in the level of oxygen in the blood (hypoxaemia). In infants born preterm, the risks of hypoxaemia, and even death are significantly greater dur ....Infants spend the major part of their life in sleep, and the period between birth and 6 months of age sees dramatic changes in their sleep organisation. Coincidently, there are dramatic developmental changes in the infant's heart and blood pressure control systems, and the ability to compensate for stress such as falls of blood pressure (hypotension) or in the level of oxygen in the blood (hypoxaemia). In infants born preterm, the risks of hypoxaemia, and even death are significantly greater during sleep than during wakefulness, but why this is so is uncertain. This study will examine the ability of infants to respond to stress during sleep. Four groups of infants will be examined: healthy infants born at normal gestation; healthy infants born prematurely (preterm); preterm infants who have experienced mild hypoxaemia soon after birth; and preterm infants who have suffered more severe hypoxaemia because of lung disease. Infants will be studied in a sleep laboratory during day-time sleep, and their ability to control blood pressure will be determined. By contrasting the effectiveness of blood pressure control between the infant groups we aim to determine whether preterm infants have lasting problems as a result of their premature birth, or their exposure to hypoxaemia. By contrasting infants in sleep and wakefulness, we aim to assess whether the risks of poorer blood pressure control are greater in sleep.Read moreRead less
Efficacy And Safety Of Methylxanthines In Very Low Birth Weight Infants
Funder
National Health and Medical Research Council
Funding Amount
$221,136.00
Summary
With improving technologies and medications the numbers of very premature babies surviving to leave hospital has increased over the last two decades. However these babies are at increased risk of having brain damage in the form of mental retardation and cerebral palsy. These problems impose a major burden on the individuals, their families and society at large. This study attempts to identify whether or not a commonly used drug is safe in these babies or whether it contributes to brain damage in ....With improving technologies and medications the numbers of very premature babies surviving to leave hospital has increased over the last two decades. However these babies are at increased risk of having brain damage in the form of mental retardation and cerebral palsy. These problems impose a major burden on the individuals, their families and society at large. This study attempts to identify whether or not a commonly used drug is safe in these babies or whether it contributes to brain damage in some cases. Many premature babies have difficulty breathing by themselves because their brain does not send regular messages to their lungs telling them to expand. A class of drugs which includes caffeine has been shown to stimulate breathing in babies and has been thought to reduce the amount of support these babies require from a ventilator in the first weeks of life. The safety of these drugs has not been adequately demonstrated in premature babies and there is some evidence from animal studies that they may disrupt the developing brain. Results in human babies are inconclusive and concerns remain regarding the long term effects of caffeine. The question of whether caffeine usage increases the risk of mental retardation or cerebral palsy is a very important one given the almost universal usage of this or similar drugs in premature babies. We will find out whether babies given caffeine as newborns perform as well at 18 months of age as babies not given the drug.Read moreRead less
The fovea is a specialized part of the retina which enables us to see fine detail. The fovea is characterised by an extremely high concentration of photoreceptor cells in a small, prescribed area to detect detail in the pattern of light reaching the retina. Each of these photoreceptor cells is connected to at least four other cells within the retina, which further refine the information coded by the photoreceptors. Because this circuitry involves so many cells, the retina has a tendency to be th ....The fovea is a specialized part of the retina which enables us to see fine detail. The fovea is characterised by an extremely high concentration of photoreceptor cells in a small, prescribed area to detect detail in the pattern of light reaching the retina. Each of these photoreceptor cells is connected to at least four other cells within the retina, which further refine the information coded by the photoreceptors. Because this circuitry involves so many cells, the retina has a tendency to be thick at the specialized area. However, in development the cells connected to the foveal photoreceptors move away from the central concentration of photoreceptors, still keeping their contacts with them. This results in thinning of the retina locally, so it has a volcanoe-like formation at the fovea, in which photoreceptors are concentrated within the crater and the displaced cells are accumulated on the rim. The events which trigger these cell displacements that form the fovea are unknown. We propose to investigate growth factors which signal between the fovea and the developing blood supply, and the relationship between the formation of the fovea and neuronal activity. This study will provide a new perspective on factors which affect central visual function and its vulnerability to insult in premature infants and in aging.Read moreRead less
The Role Of Arousal And Respiratory Control Factors In The Pathogenesis Of Obstructive Sleep Apnoea
Funder
National Health and Medical Research Council
Funding Amount
$567,924.00
Summary
Sleep apnoea (OSA) is a very common breathing disorder in sleep characterized by repetitive closure of the collapsible portion of the throat with serious effects on sleep quality and health. Basic causes of OSA are still largely unknown. We will investigate waking responses to breathing load and related respiratory control factors that we believe may be fundamental causes of OSA, and potentially explain many features of OSA including worsening in light sleep and with increasing age.
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
A Novel Treatment For Ameliorating Retinal Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$366,685.00
Summary
Retinal vascular disease is a leading cause of blindness and is currently treated by laser photocoagulation surgery. Although successful, this treatment is associated with serious side effects. Recently, Ellex Pty has developed a novel laser called the 2RT laser that is likely to be effective without the accompanying side effects. This study will allow examine the effect of the 2RT laser in animal models of retinal vascular disease so as to complete preclinical development of this laser.
The Significance Of Glial Dysfunction In Retinopathy Of Prematurity
Funder
National Health and Medical Research Council
Funding Amount
$311,567.00
Summary
Abnormalities in cells at the back of the eye called photoreceptors are associated with at least 50% of all cases of blindness in this country.This project will determine whether substances released from dying photoreceptors cause the death of neighbouring cells. In addition we will examine whether treatments that block the actions of these released substances can prevent the death of photoreceptors, thereby providing a novel therapeutic agent for the treatment of devastating eye diseases.
Interactions Between Vasoactive, Epigenetic And Immunogenic Pathways In The Development Of Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$664,584.00
Summary
In our community, diabetic retinopathy is the leading cause of vision loss in people of working age. As the prevalence of diabetic retinopathy increases, there is an urgent need to understand the factors that cause its development in order to develop new treatments. This proposal will explore the contribution of hormones, the memory of retinal cells to high glucose and stress, and the immune system to diabetic retinopathy. The goal is to develop new and improved treatments for Australians.