Mortality And Survival Among Clients Of The Aboriginal Medical Service At Redfern
Funder
National Health and Medical Research Council
Funding Amount
$483,290.00
Summary
The aims of the mortality study are to: (a) document current age-sex specific and cause-specific Indigenous mortality; (b) establish trends in age-sex specific and cause-specific Indigenous mortality over time; (c) compare age-sex-cause specific mortality in the AMS Redfern cohort with patterns documented in other Aboriginal populations, and in the general Australian population. The null hypotheses for general and cause-specific mortality (age-adjusted) are that: (a) there has been no decline in ....The aims of the mortality study are to: (a) document current age-sex specific and cause-specific Indigenous mortality; (b) establish trends in age-sex specific and cause-specific Indigenous mortality over time; (c) compare age-sex-cause specific mortality in the AMS Redfern cohort with patterns documented in other Aboriginal populations, and in the general Australian population. The null hypotheses for general and cause-specific mortality (age-adjusted) are that: (a) there has been no decline in mortality in Aboriginal people attending AMS Redfern over 30 years covering 1972-2001; (b) survival in the AMS cohort is similar to that recorded in Aboriginal people from NT and WA (mostly rural) for similar time periods; (c) comparisons of the AMS cohort mortality with overall NSW mortality are similar to previously published comparisons of NT-WA Aboriginal mortality compared to overall Australian mortality data. Major causes of mortality will centre on endocrine (mainly diabetes), cardio- and cerebro-vascular diseases, and on external causes, including suicide-violence and accidental death. The mortality study will be extended back to the inception of the AMS, and will rely on computerisation of name(s), sex, date of birth and date of first and last AMS attendance for the whole AMS patient data base, to provide information for matching of patient records with the National Death Index (for deaths from 1980) and for matching with the NSW mortality data for 1971-79 (as there is no nationwide mortality data available from a single source prior to 1980).Read moreRead less
Regulation Of Prostaglandin Endoperoxide Synthase-2 In The Human Fetal Membranes At Birth
Funder
National Health and Medical Research Council
Funding Amount
$249,750.00
Summary
Preterm birth with the resulting immaturity of babies is the leading cause of death and disease among newborns. Early birth occurs in 6 to 11% of pregnancies, and its rate is slowly increasing in industrialized countries. We need a much better knowledge of the regulation of the parturition process to find ways to reverse this trend. Prostaglandins are hormonal substances that stimulate uterine contractions, cervical dilatation and membrane rupture. Intrauterine tissues produce prostaglandins, an ....Preterm birth with the resulting immaturity of babies is the leading cause of death and disease among newborns. Early birth occurs in 6 to 11% of pregnancies, and its rate is slowly increasing in industrialized countries. We need a much better knowledge of the regulation of the parturition process to find ways to reverse this trend. Prostaglandins are hormonal substances that stimulate uterine contractions, cervical dilatation and membrane rupture. Intrauterine tissues produce prostaglandins, and an increase of prostaglandin levels in the uterus is likely responsible for inducing labour both normally and preterm. We have previously identified an enzyme protein in the fetal membranes, called prostaglandin synthase-2, that has a key role in the synthesis of intrauterine prostaglandins during pregnancy. This enzyme is increasingly expressed before labour onset. In the present application, we propose studies to determine what causes the increased expression. We hypothesize that the gene encoding this enzyme is specifically activated in the fetal membranes in preparation for labour. We will define the mechanism of regulation by determining the activity of the gene in tissues from women who deliver either spontaneously or without labour at term and preterm. Further, we will determine the interaction of regulatory proteins with the prostaglandin synthase-2 gene in these pregnancies in order to understand the mechanisms of regulation at the molecular level. Finally, we will conduct cell culture studies to experimentally manipulate prostaglandin synthase-2 gene activity in fetal membrane cells. As an overall outcome of this work, new targets may be identified for drugs to disrupt prostaglandin synthase-2 gene activation specifically in the fetal membranes. The long term perspective is to block prostaglandin synthesis in the uterus in order to suppress preterm labour and prevent preterm birth.Read moreRead less
Antagonist Of Corticotrophin Releasing Hormone As Therapeutic Agents For The Prevention Of Premature Birth In Humans
Funder
National Health and Medical Research Council
Funding Amount
$376,650.00
Summary
In developed countries the most common cause of the death of a newborn baby is premature delivery. Pre-term delivery remains the greatest cause of neonatal mortality in the western world and a major consumer of health dollars (approx. $5-7B per year in the US alone). However, a delay in the onset of labour from 20 to 25 weeks has been shown to result in a 55% greater probability of infant survival (550 fewer deaths per 1000). This project will allow: The development of new drugs that will allow ....In developed countries the most common cause of the death of a newborn baby is premature delivery. Pre-term delivery remains the greatest cause of neonatal mortality in the western world and a major consumer of health dollars (approx. $5-7B per year in the US alone). However, a delay in the onset of labour from 20 to 25 weeks has been shown to result in a 55% greater probability of infant survival (550 fewer deaths per 1000). This project will allow: The development of new drugs that will allow the extension of pregnancy term The development of protocols that will in turn reduce neonatal mortality. Additionally we believe that these new agents will be useful in preventing the onset of labour after fetal surgery. Currently there are no effective treatments capable of substantially changing delivery dates. Available therapeutics delay the onset of labour, at best, 24 hours. However, recent exciting results from our laboratories show that rising concentrations of the placental peptide Corticotrophin Releasing Hormone (CRH) are associated with the onset of labour. Further, we have also delayed the onset of labour in pregnant sheep by infusing a relatively insoluble CRH antagonist into the sheep fetus. Labour commenced ONLY AFTER the drug was withdrawn from the mother. This project builds upon an interdisciplinary team: medicinal chemists, molecular modellers, pharmacologists and endocrinologists, to further develop an exciting Australian discovery. Successful completeion of this research will, for the first time, allow the control of pregnancy duration MAXIMISING the benefits to mother and child, reducing mortality and later life morbidities typically associated with premature birth.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
Mechanisms Of Escape From Progesterone-induced Suppression: Role In Normal And Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Prematurity caused by preterm birth is the leading cause of death and disease among newborns in Australia. Here we will define how the length of pregnancy is determined by the opposing actions of progesterone, which maintains pregnancy, and prostaglandins, which induce labour. We will demonstrate the mechanism by which the actions of the two hormones are balanced in normal pregnancy and disrupted in preterm labour. We will show that preterm birth can be prevented by correcting the disorder.
This project will test if the ratio of the two different estrogens found in the blood of pregnant women is the critical factor in determining the onset of contractions in the uterus at labour. The studies will also determine the role of a newly discovered receptor for estrogens in allowing powerful contractions at labour. Results will allow development of new treatments to prevent premature birth that block the actions of estrogen at this new receptor or change the ratio of the two estrogens.
Regulation Of Progesterone Action In Human Parturition.
Funder
National Health and Medical Research Council
Funding Amount
$314,983.00
Summary
Premature birth is the leading cause of neonatal death and sickness, and numbers are increasing due to our ignorance of the biology of labour. Progesterone maintains pregnancy and its withdrawal results in birth, but how this is achieved in humans is unknown. This project will determine the molecular mechanisms by which progesterone action is regulated during the transition from pregnancy to birth. This data will guide new strategies to prevent premature birth.