Evaluation Of Nitrous Oxide In The Gas Mixture For Anaesthesia: A Randomised Controlled Trial (The ENIGMA Trial)
Funder
National Health and Medical Research Council
Funding Amount
$490,125.00
Summary
There are about 2 million anaesthetics given each year in Australia (1:10 Australians), with more than 1 million Australians being exposed to nitrous oxide (laughing gas). Despite being around for more than 150 years, there has yet to be a large trial of the safety and benefits of nitrous oxide, particularly when compared with newer (safer?) anaesthetic drugs. Nitrous oxide is not a particularly strong anaesthetic and so it must be mixed with other drugs. Current practice in Australia and around ....There are about 2 million anaesthetics given each year in Australia (1:10 Australians), with more than 1 million Australians being exposed to nitrous oxide (laughing gas). Despite being around for more than 150 years, there has yet to be a large trial of the safety and benefits of nitrous oxide, particularly when compared with newer (safer?) anaesthetic drugs. Nitrous oxide is not a particularly strong anaesthetic and so it must be mixed with other drugs. Current practice in Australia and around the world is to give 70% nitrous oxide in oxygen along with another anaesthetic gas in order to produce a depth of anaesthesia sufficient for surgery. This is despite knowledge that nitrous oxide interferes with the production of DNA. DNA is used to programme cell division and function - it is the building block of cell and tisue growth. It is known that nitrous oxide can impair some tissue functions, such that anaemia and, possibly birth defects can occur. Such effects are rare, but recent evidence suggests that milder abnormalities may occur more commonly than previously thought. There is also good evidence that nitrous oxide increases the risk of severe nausea and vomiting after surgery. The adverse effects on DNA production raises the possibility of nitrous oxide causing immune deficiency, heart ischaemia, (angina), nerve and spinal cord damage, and increased cancer risk in hospital staff chronically exposed to low levels of nitrous oxide. The prevailing view is that nitrous oxide is a cheap, relatively safe drug that can reduce the exposure to other anaesthetic drugs. However, the development of many new anaesthetic drugs demands a re-evaluation of the role of nitrous oxide in current anaesthetic practice.Read moreRead less
Minimising Disability And Falls In Older People Through A Post-hospital Individualised Exercise Program.
Funder
National Health and Medical Research Council
Funding Amount
$536,435.00
Summary
This study aims to implement and evaluate the Functional Activities for Better Balance (FABB) program, a tailored exercise program which is designed to minimise disability and falls, among older adults who have recently had a hospital stay. A randomised controlled trial will be undertaken to determine the success of the program in minimising disability and falls and improving balance, muscle strength, and reaction time, quality of life and fear of falling. In addition, predictors of adoption of ....This study aims to implement and evaluate the Functional Activities for Better Balance (FABB) program, a tailored exercise program which is designed to minimise disability and falls, among older adults who have recently had a hospital stay. A randomised controlled trial will be undertaken to determine the success of the program in minimising disability and falls and improving balance, muscle strength, and reaction time, quality of life and fear of falling. In addition, predictors of adoption of and adherence to the exercise program and the cost effectiveness of the program will be established. We will recruit 350 older people in the first six months after an in-patient stay in aged care and rehabilitation wards at one of two large teaching hospitals. Participants randomised to the intervention group will be asked to complete an individualised home exercise program three times a week. In addition, they will be offered a choice between receiving monthly physiotherapy home visits or attending exercise classes. These weekly exercise classes will be conducted by physiotherapists and will be made up of 6-8 people. The control group will receive an education booklet about falls prevention and will be given the opportunity to join the program on a self-funding basis after their one-year control period is complete. Post-intervention between-group comparisons will be made using appropriate statistical techniques including regression models. Additional analyses will establish predictors for program adoption and adherence and cost-effectiveness (the incremental cost per fall prevented in the exercise group compared with the control group). This study addresses an increasingly important health care problem in a systematic manner and thus has the potential to substantially enhance the health of older people in Australia and internationally.Read moreRead less
Prediction Of Clinical Radiosensitivity Caused By Ionising Radiation During Radiotherapy.
Funder
National Health and Medical Research Council
Funding Amount
$447,750.00
Summary
Around one to five percent of cancer patients suffer from significant side effects in normal tissue exposed to ionizing radiation during radiotherapy. Although radiotherapy is an effective therapy for cancer treatment, the amount of radiation is generally restricted to minimize the incidence of these severe side effects (radiosensitivity). This means that individuals who don't have radiosensitivity are not getting the dose of radiation that would be most beneficial. A major goal of radiation bio ....Around one to five percent of cancer patients suffer from significant side effects in normal tissue exposed to ionizing radiation during radiotherapy. Although radiotherapy is an effective therapy for cancer treatment, the amount of radiation is generally restricted to minimize the incidence of these severe side effects (radiosensitivity). This means that individuals who don't have radiosensitivity are not getting the dose of radiation that would be most beneficial. A major goal of radiation biology research is to develop efficient predictive measures that could identify radiosensitive individuals prior to treatment. This predictive ability would enable the individualisation of radiotherapy radiation doses, which should result in improvement of tumour control rates and a reduction in the incidence of side effects associated with radiotherapy. We aim to understand radiosensitivity at the molecular level using the powerful technology of microarrays. Using microarray technology, thousands of genes can be tested for expression activity simultaneously. We have a unique tissue bank established from many radiosensitive and non-sensitive control radiotherapy patients. The use of microarray technology on samples from this unique tissue bank may enable the gene expression pattern of individuals that display radiosensitivity to be distinguished from the rest of the population. In conjunction, two additional tests will be used to determine who is susceptible to radiosensitive reactions which include assessment of a DNA repair pathway and assessment of the length of the telomeres (Caps on the ends of the chromosomes), both of which have been shown to be involved with radiosensitivy. This experimentation will hopefully lead to the development of a predictive assay for use in the clinic for cancer patients prior to receiving radiotherapy.Read moreRead less
Neuroendocrine Mechanisms By Which Leptin Regulates Reproduction
Funder
National Health and Medical Research Council
Funding Amount
$447,750.00
Summary
The reproductive system is sensitive to alterations in body weight. In particular, low body weight causes the reproductive system to cease functioning. This is because the brain 'senses' metabolic status and responds by ceasing to secrete the brain hormone that drives the reproductive process. This hormone is gonadotropin releasing hormone that acts on the pituitary gland to control the release of gonadotropins. These, in turn, act on the gonads. How the brain perceives metabolic status is not k ....The reproductive system is sensitive to alterations in body weight. In particular, low body weight causes the reproductive system to cease functioning. This is because the brain 'senses' metabolic status and responds by ceasing to secrete the brain hormone that drives the reproductive process. This hormone is gonadotropin releasing hormone that acts on the pituitary gland to control the release of gonadotropins. These, in turn, act on the gonads. How the brain perceives metabolic status is not known. Leptin is a hormone that is produced by fat and acts on the brain. This appears to be one of the means by which the reproductive system is regulated. Leptin also regulates food intake and other brain processes. Leptin acts on specific cell types in the brain. Some of these may have dual function to regulated appetite as well as reproduction. The present proposal is for work to determine mechanisms within the brain that are altered by leptin. We will also determine which specific mechanisms relate to the regulation of gonadotropin releasing hormone. The work will provide information on how putative appetite regulators might affect the reproductive axis. Such work will provide a platform for design of pharmaceutical means to manipulate the reproductive axis and will impact on the design of drugs that regulate obesity. It is possible that drugs that developed to control obesity may affect the reproductive axis and the project will identify these.Read moreRead less
Physiological Mechanisms Of Efficacy Of Cervical Flexor Muscle Retraining
Funder
National Health and Medical Research Council
Funding Amount
$264,750.00
Summary
Neck pain is a significant problem in society and its frequency is beginning to match the proportions of back pain, probably reflecting our increasingly sedentary lifestyles. Several problems have been identified in the muscle system in persons who suffer from neck pain. Therapeutic exercise has been found to have benefit in preventing and relieving pain and improving the neck function. Currently there are several, quite different methods of exercise and there is controversy regarding how therap ....Neck pain is a significant problem in society and its frequency is beginning to match the proportions of back pain, probably reflecting our increasingly sedentary lifestyles. Several problems have been identified in the muscle system in persons who suffer from neck pain. Therapeutic exercise has been found to have benefit in preventing and relieving pain and improving the neck function. Currently there are several, quite different methods of exercise and there is controversy regarding how therapeutic exercise works. It has been argued that parameters such as changes in muscle strength, endurance, joint position sense or muscle coordination may be responsible for the clinical efficacy. It is difficult to disentangle the effective component of exercise strategies and thus prescribe the most effective exercise strategies. This series of experiments will evaluate the physiological factors that change with a specific exercise intervention and to compare different exercise modalities in order to identify the most effective means to induce these changes. Cervical muscle training, using a proven exercise intervention strategy for chronic neck pain and headache, has been chosen as the model to investigate these questions. This exercise strategy has been chosen not only because it has been shown to be effective, but also because it does not conform to contemporary rationales for strength or endurance training. Thus while effective in relieving pain, it is unlikely to produce changes in these parameters. Thus other mechanisms are likely to be responsible for the clinical change. This research stands to make a significant contribution to exercise therapeutics by identifying the effective components of different exercise methods and investigating the pain relieving effects of the specific exercise. This knowledge will lead to the construction of a research based exercise program for neck pain patients, rather than have the current situation of often arbitrary choice of exercise.Read moreRead less
LIM KINASE 1 (LIMK1) AND METASTASIS, THE SEARCH FOR LIMK1 INHIBITORS
Funder
National Health and Medical Research Council
Funding Amount
$461,250.00
Summary
Disseminated cancer, unlike the localized disease, can rarely be cured by drug therapy. We have found that LIM kinase (LIMK1), a protein that was discovered in our laboratory, plays an important role in controlling the ability of tumour cells to spread, a process called metastasis. Thus, this protein becomes an important target for the development of new drug therapies to prevent the spread of cancer. Importantly, we have demonstrated that (1) inhibiting LIMK1 blocks the formation of metastatic ....Disseminated cancer, unlike the localized disease, can rarely be cured by drug therapy. We have found that LIM kinase (LIMK1), a protein that was discovered in our laboratory, plays an important role in controlling the ability of tumour cells to spread, a process called metastasis. Thus, this protein becomes an important target for the development of new drug therapies to prevent the spread of cancer. Importantly, we have demonstrated that (1) inhibiting LIMK1 blocks the formation of metastatic tumours in mice, and (2) introduction of this protein into tumour cells makes them more invasive. In addition, we find that the level of LIMK1 is much higher in human tumour cell lines that have the propensity to easily form tumours in mice. Also, measuring the level of this protein in cancer cells that spread to other organs shows that it is at significantly elevated levels when compared to normal tissue. The goals of this research are to: (1) understand whether the ability of LIMK1 to regulate tumour spreading and invasiveness correlates with its ability to control metastasis; (2) examine in human tumour samples whether the levels of LIMK1 correlate with the development of metastatic tumours; and (3) search for drugs that can inhibit the activity of this protein. The results from this research will be highly significant because LIMK1 levels are likely to be an important marker for which tumours will become metastatic. It is possible that, at the time of tumour diagnosis, LIMK1 measurements will enable the clinician to predict whether an individual tumour will become metastatic. Secondly, this protein is a novel drug development target. Drugs that inhibit this protein may block the ability of tumours to invade and metastasise.Read moreRead less
Improved Ways To Study The Effect Of Transient Exposures On The Risk Of An Illness, With Application To Flying And DVT
Funder
National Health and Medical Research Council
Funding Amount
$212,250.00
Summary
Improved methods of analysis will be developed to estimate the extent to which certain short-term activities trigger a particular illness and to determine who is most at risk. The new methods of analysis have many potential applications, including study of the effect of periods of intense exercise or intense alcohol consumption on the risk of a heart attack. Here we apply them to study the effect of air travel on illness due to blood clots in a vein (deep vein thrombosis, DVT), and the factors t ....Improved methods of analysis will be developed to estimate the extent to which certain short-term activities trigger a particular illness and to determine who is most at risk. The new methods of analysis have many potential applications, including study of the effect of periods of intense exercise or intense alcohol consumption on the risk of a heart attack. Here we apply them to study the effect of air travel on illness due to blood clots in a vein (deep vein thrombosis, DVT), and the factors that put individuals at greatest risk. The extra understanding that our improved analysis of the data provides will accelerate research into ways to minimise the risk of flight-induced DVT and implementation of preventative measures in the travel industry. This has the potential to prevent many cases, and deaths, because the number of flights taken, globally, by individuals in a year is now in the billions. Specifically, dependence of flight-induced DVT on age, sex, being pregnant, recent fractures and having certain cancers will identify individuals at greatest risk, while dependence on the duration of the flight will identify flights that present greater risk. The development of these new methods of analysis will make a lasting contribution to public health research, because they can be used to study many short-term-activity - illnesses combinations. The methods will see increasing applications because the type of data they rely on, namely the complete history of exposures over time periods, will increasingly become available as electronic recording of activities becomes more common place. For example, electronic records of flights are now almost universal and bookings at squash courts and other sporting venues are increasingly recorded electronically. The computer software to apply the new methods of analysis will be made available to other researchers, to promote studies of this type.Read moreRead less