The Interaction Between Sexually Transmissible Infections And Human Immunodeficiency Virus Infection In Homosexual Men
Funder
National Health and Medical Research Council
Funding Amount
$635,931.00
Summary
This project examines the inter-relationship between HIV infection and sexually transmitted infections (STIs) in homosexual men. The overall goal of the projet is to inform the development of STI prevention and treatment strategies which may be important in reducing HIV incidence in this population. Homosexual men comprise over 80% of people diagnosed with HIV infecton in Australia, and in many developed nations are one of the largest groups affected by HIV. Rates of other STIs are also increase ....This project examines the inter-relationship between HIV infection and sexually transmitted infections (STIs) in homosexual men. The overall goal of the projet is to inform the development of STI prevention and treatment strategies which may be important in reducing HIV incidence in this population. Homosexual men comprise over 80% of people diagnosed with HIV infecton in Australia, and in many developed nations are one of the largest groups affected by HIV. Rates of other STIs are also increased in homosexual men. Currently, HIV rates are increasing in Australia and in many developed countries. We are in need of new and effective methods of HIV prevention. Data in heterosexuals suggest that where STIs are common, the early detection and treatment of these infections may help reduce HIV incidence. There are few data on this relationship in homosexual men. We propose to utilise an existing Sydney cohort of homosexual men to collect data on biologic tests for STIs, history of recent diagnosis of STIs, and symptoms, to allow a comprehensive description of the epidemiology of STIs and their overlap with HIV. The quality of data on the interaction between HIV and STIs in this cohort will be superior to any previously collected in homosexual men, as it will include data on self-reported doctor diagnosed illness, state of the art biologic testing, and symptom data, for the full spectrum of important STIs. The results of this study will be helpful in determining strategies for HIV and STI screening, education and control in the population which comprises the great majority of cases of HIV infection in Australia, and one of the largest risk groups for HIV infection in the developed world. Screening coupled with treatment of asymptomatic STIs may be an effective new approach to HIV prevention in this population.Read moreRead less
The prevalence of asthma in Australia is amongst the highest in the world yet no trials of primary prevention have been conducted which address the most common known causative agent (housedust mite allergens) and the most common known protective factor (dietary omega-3 fatty acids). Until the effectiveness of interventions which address these factors is certain, the value of the wide array of advice given to asthmatics by various health institutions will not be known. We are applying to continue ....The prevalence of asthma in Australia is amongst the highest in the world yet no trials of primary prevention have been conducted which address the most common known causative agent (housedust mite allergens) and the most common known protective factor (dietary omega-3 fatty acids). Until the effectiveness of interventions which address these factors is certain, the value of the wide array of advice given to asthmatics by various health institutions will not be known. We are applying to continue the Childhood Asthma Prevention Study (CAPS) which has been underway since mid-1997. CAPS is a randomised controlled trial in which 616 infants at high risk of developing asthma because of a family history have been enrolled. The interventions include allergen reduction and dietary supplementation with omega-3 fatty acids. The interventions are designed to have maximum effect but be simple to implement by parents. Several measures of compliance are being collected and regular contact is maintained though telephone calls and frequent home visits. Objective and subjective measurements of exposures, atopy, diet and asthmatic symptoms are being collected at 3 month intervals and at medical assessments when the children are 18 months, 3 and 5 years old. It is essential that we continue the study until all children are aged 5 and we will be able to test conclusively whether the interventions have had a positive effect. If so, CAPS will form the basis for a nationwide public health campaign which will have the potential to reduce the incidence of childhood asthma in Australia.Read moreRead less
Pandemic Influenza Containment Strategies In Aboriginal Communities: What Is Acceptable And Feasible?
Funder
National Health and Medical Research Council
Funding Amount
$1,056,688.00
Summary
Influenza is a serious disease with a much greater impact in Indigenous communities. This project will work with Aboriginal communities in NSW, north Qld and WA on modifying the national pandemic influenza plan to develop control strategies that are acceptable to the culture and circumstances of those communities. A template and acceptable process will then be offered to other Indigenous communities, finally leading to negotiation to modify implementation of pandemic influenza plans.
An Implementation Trial Of A Telephone-based Care Management Program For Patients Following Myocardial Infarction
Funder
National Health and Medical Research Council
Funding Amount
$641,656.00
Summary
We are trialling the implementation of an innovative telephone-delivered program for managing people who have had a heart attack. Cardiac rehabilitation programs are generally based in hospitals in Australia and people have to be able to attend the programs when they are offered. Even though such programs have been shown to be very effective in improving outcomes after a heart attack, at least 85% of Australians after a heart attack are either unable to access and-or unable to attend such progra ....We are trialling the implementation of an innovative telephone-delivered program for managing people who have had a heart attack. Cardiac rehabilitation programs are generally based in hospitals in Australia and people have to be able to attend the programs when they are offered. Even though such programs have been shown to be very effective in improving outcomes after a heart attack, at least 85% of Australians after a heart attack are either unable to access and-or unable to attend such programs due to transport and many other barriers. So, there is an urgent need to identify new, effective, and affordable ways of delivering cardiac rehabilitation programs to people after a heart attack. The proposed telephone-delivered program will be particularly appropriate for disadvantaged people, such as those living in rural and remote areas as well as Indigenous Australians, who do not currently have access to hospital-based cardiac rehabilitation programs. People who have had a heart attack will be recruited from three of Brisbane's largest public teaching hospitals, and will then be randomly assigned to the telephone-delivered cardiac rehabilitation program (Care Management Intervention group) or to a control or Usual Care group. The Care Management Intervention group will receive regular telephone calls from a highly qualified 'Care Manager' based at the renowned National Heart Foundation of Australia telephone support service, 'Heartline'. The Care Manager will help people to manage their heart condition and prevent the reoccurrence of further heart problems. People will also be encouraged to make necessary lifestyle and behavioural changes with the assistance of the Care Manager and some Heart Foundation educational and interactive resources to record their progress. We expect that the program or Care Management Intervention group will have better health outcomes than the control or Usual Care group at 6 and 12 months follow up.Read moreRead less
Environmental Influences On Allergic Airways Disease From Birth To 8yrs: Long-term Outcomes Of A Randomised Trial (CAPS)
Funder
National Health and Medical Research Council
Funding Amount
$530,000.00
Summary
The prevalence of asthma in Australia is among the highest in the world yet no trials of primary prevention have been conducted which address the most common known causative agent (housedust mite allergens) and the most common known protective factor (dietary omega-3 fatty acids). Until the effectiveness of interventions which address these factors is certain, it will not be possible to give confident advice about how to prevent asthma. We are applying to continue follow up of the cohort of the ....The prevalence of asthma in Australia is among the highest in the world yet no trials of primary prevention have been conducted which address the most common known causative agent (housedust mite allergens) and the most common known protective factor (dietary omega-3 fatty acids). Until the effectiveness of interventions which address these factors is certain, it will not be possible to give confident advice about how to prevent asthma. We are applying to continue follow up of the cohort of the Childhood Asthma Prevention Study (CAPS) which has been underway since mid-1997. CAPS is a randomised controlled trial in which 616 infants at high risk of developing asthma because of a family history have been enrolled. The interventions include allergen reduction and dietary supplementation with omega-3 fatty acids. The interventions are designed to have maximum effect but be simple to implement by parents. Objective and subjective measurements of exposures, atopy, diet and asthmatic symptoms are being collected at 3 month intervals and at medical assessments when the children are 18 months, 3 and 5 years old. The interventions are stopped at age 5 years. The continued follow up of the cohort to age 8 will enable us to test conclusively if the interventions have had a positive effect. If so, CAPS will form the basis for a nationwide public health campaign which will have the potential to reduce the incidence of childhood asthma in Australia.Read moreRead less
This proposal is designed to test the protein leverage hypothesis (PLH) in humans: the idea that the level of food consumption in humans, like other animals, is adjusted to maintain a target protein intake. As the prevalence of overweight and obesity increases, with its attendant health problems, the need to identify which dietary components limit rather than exacerbate energy intake is imperative. According to the PLH, the consumption of a diet low in % protein and high in % fat and carbohydrat ....This proposal is designed to test the protein leverage hypothesis (PLH) in humans: the idea that the level of food consumption in humans, like other animals, is adjusted to maintain a target protein intake. As the prevalence of overweight and obesity increases, with its attendant health problems, the need to identify which dietary components limit rather than exacerbate energy intake is imperative. According to the PLH, the consumption of a diet low in % protein and high in % fat and carbohydrate, typical of many Western countries, inevitably requires the ingestion of additional energy to maintain protein intake constant, thus driving weight gain. Conversely, the consumption of a diet that is relatively high in % protein requires the ingestion of lower levels of energy, creating the potential for weight loss. Preliminary experimental and population-level nutritional survey data support the PLH, as does the finding that protein is more satiating than other macronutrients. If, as predicted, small changes in the proportion of protein in diets described in the current study are found to impact on total energy intake there will be significant implications for weight control strategies. Thus, if the PLH is confirmed, public health dietary recommendations and government policy settings for the food industry will need to change. Large-scale intervention studies aimed at demonstrating the longer term impact on body weight will also be required.Read moreRead less
Mitochondrial Iron Overload And Friedreich's Ataxia: The Role Of Frataxin In Iron And Haem Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$285,990.00
Summary
Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. Recent studies using Baker's yeast have shown that the deletion of frataxin results in the accumulation of toxic iron in the mitochondrion. More recently, a variety of studies have shown that FA patients have iron loading within their cells. The iron build-up may cause severe damage. At present, the role of frataxin in mammalian mitochondrial iron metabolism is unknown. Our preliminary studies demonstrate that frataxin i ....Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. Recent studies using Baker's yeast have shown that the deletion of frataxin results in the accumulation of toxic iron in the mitochondrion. More recently, a variety of studies have shown that FA patients have iron loading within their cells. The iron build-up may cause severe damage. At present, the role of frataxin in mammalian mitochondrial iron metabolism is unknown. Our preliminary studies demonstrate that frataxin is down-regulated by either erythroid differentiation or the haem precursor protoporphyrin IX (Becker and Richardson, submitted). These data strongly suggest a role for frataxin in iron metabolism. In the present study we will continue to assess if frataxin plays a role in the way cells handle iron. Using a unique model of mitochondrial iron overload developed in my lab (Richardson et al. (1996) BLOOD 87:3477), we will extensively investigate the iron metabolism of the mitochondrion in order to determine the function of frataxin and its role in Friedreich's ataxia. In addition, we have developed a series of new drugs known as iron chelators that can enter the mitochondrion due to their high lipid solubility (Becker and Richardson 1999 J. Lab. Clin. Med. 134:510). These latter drugs are far more effective than the chelator currently used to treat iron overload, desferrioxamine (DFO). Indeed, our chelators have been designed to result in high iron chelation efficacy but low toxicity (see Becker and Richardson, 1999). This exciting research may be crucial in understanding the development of FA and in creating new therapies such as the use of iron chelators.Read moreRead less
The Effect Of Exogenous Hormones, Smoking And HPV On The Incidence Of Screen Detected Pre-invasive Cervical Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$1,201,168.00
Summary
Cervical cancer is one of the leading causes of cancer death in women internationally. About 15,000 women are detected in NSW annually as having pre-invasive cervical cancer (cervical intraepithelial neoplasia (CIN) grade I, II or III). Infection with certain high risk human papillomaviruses is known to be necessary for the development of cervical cancer. In addition, recent long term exposure to smoking and to hormonal contraception are two new factors considered as independent risk factors for ....Cervical cancer is one of the leading causes of cancer death in women internationally. About 15,000 women are detected in NSW annually as having pre-invasive cervical cancer (cervical intraepithelial neoplasia (CIN) grade I, II or III). Infection with certain high risk human papillomaviruses is known to be necessary for the development of cervical cancer. In addition, recent long term exposure to smoking and to hormonal contraception are two new factors considered as independent risk factors for the disease. Hormone replacement therapy (HRT) preparations taken around the menopause are a similar composition to hormonal contraceptives, (oestrogen and progestogen), therefore women on HRT may also be at increased risk. No comprehensive study exists internationally to measure the relative importance of these exogenous hormones on the development of pre-invasive cervical cancer in a way that is of public health relevance (e.g. recent long-term use of oral contraceptives and time since stopped, and among smokers and non-smokers). No Australian data are available on the proportion of women who are current users of hormonal contraceptives or HRT. No local prevalence data on the major high risk HPV subtypes (e.g. 16, 18, 33, 45) are available for Australia to describe its distribution and to inform the cervical screening program and future vaccine initiatives. The NSW Pap Test Register holds the screening history of all women on the cervical screening program, hence this is an ideal source for recruiting a representative sample into a study. We wish to conduct a large study of ~2600 NSW women using the NSW Pap Test Register to measure the relative importance of hormones, smoking and HPV infection on the development of CIN II or III.Read moreRead less
Mitochondrial Iron Overload And Friedreich's Ataxia: The Role Of Frataxin In Iron And Haem Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$606,000.00
Summary
Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. A variety of studies using Baker's yeast and conditional frataxin knockout (KO) mice have shown that deletion of frataxin leads to the accumulation of toxic iron in their mitochondrion. More recently, a variety of studies have shown that FA patients have iron-loading within their mitochondrion. Iron in the highly redox active environment of the mitochondrion could contribute to the generation of cytotoxic radicals that c ....Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. A variety of studies using Baker's yeast and conditional frataxin knockout (KO) mice have shown that deletion of frataxin leads to the accumulation of toxic iron in their mitochondrion. More recently, a variety of studies have shown that FA patients have iron-loading within their mitochondrion. Iron in the highly redox active environment of the mitochondrion could contribute to the generation of cytotoxic radicals that cause severe damage. Further, cells deficient in frataxin are sensitive to oxidant stress and Fe chelators rescue oxidant-mediated death of cells from FA patients. Indeed, free radical scavengers have shown to be of use in the treatment of this disease. Studies in DR's lab during this NHMRC grant have shown that frataxin is down-regulated by erythroid differentiation or the haem precursor, protoporphyrin IX (BLOOD 2002;99:3813-22). These data indicate a role for frataxin in Fe metabolism and the pathogenesis of FA. In this study we will continue to examine the role of frataxin in the way cells handle Fe using experimental models developed under the current NHMRC grant. These include transfected cell lines with low frataxin expression generated using an expression vector containing anti-sense frataxin cDNA. Further we obtained the frataxin conditional KO mouse and generated a breeding colony. These animals display many of the pathological features of FA and are the best current model of the disease. Indeed, they will be critical for assessing the role of frataxin in Fe metabolism and as a model to test the ability of Fe-binding drugs to prevent the pathology observed. We designed lipid-soluble chelators that can enter the mitochondrion to bind Fe (Biochim Biophys Acta 2001;1536:133-140) and these ligands will be tested to prevent disease progression in the KO mice. This exciting research is crucial for understanding the pathogenesis of FA and in creating new therapies.Read moreRead less
A Randomised Placebo-controlled Trial Of Antibiotics To Prevent Urinary Tract Infection In Children
Funder
National Health and Medical Research Council
Funding Amount
$735,000.00
Summary
This study is needed to determine whether a common clinical practice long-term antibiotic treatment for children following urinary tract infection (UTI) - is safe and effective in preventing further UTI and if so, whether all appropriate children are being treated. UTI will affect about 10% of Australian children by high school age (88,000 children per year). Because UTI may damage the kidneys, the management priority for children with UTI has been prevention of further infection. Currently this ....This study is needed to determine whether a common clinical practice long-term antibiotic treatment for children following urinary tract infection (UTI) - is safe and effective in preventing further UTI and if so, whether all appropriate children are being treated. UTI will affect about 10% of Australian children by high school age (88,000 children per year). Because UTI may damage the kidneys, the management priority for children with UTI has been prevention of further infection. Currently this means the identification of children thought to be most at risk of recurrent UTI by renal tract imaging. Those found to have reflux of urine from the bladder to the kidney (present in about 30% of those with UTI) are then placed on antibiotics fro 2-5 years. Unfortunately there has never been a properly designed trial to test whether antibiotics do really prevent UTI and if so, whether children with reflux are the appropriate and only group requiring treatment. Long term antibiotics may in fact do more harm than good because of side effects like skin, bowel and blood problems and because resistant bacteria may develop. The design of this study involves the random allocation of placebo or antibiotic (cotrimoxazole, the usual antibiotic given in this case) to about 800 children after their first symptomatic UTI. These children are treated and followed for one year to determine the rate of futher UTI in both groups. Any difference in outcome between the two groups of children will be because of the antibiotic treatment. This study may prove long-term antibiotics are ineffective and therefore should not be routinely used. In this case investigation of children to detect vesicoureteric reflux would serve little purpose and should be abandoned. Alternatively antibiotic treatment may be shown as effective treatment for preventing further UTI and in this case the study will clearly identify those children who will benefit.Read moreRead less