Non-neuronal ATP: Regulation Of Release And Action In The Bladder
Funder
National Health and Medical Research Council
Funding Amount
$451,553.00
Summary
Incontinence disorders are costly and debilitating. How the bladder signals the normal sensation of fullness as well as the urgent need to void urine (urgency) is still not fully understood. The signaling molecule ATP is released during bladder stretch. Using animal and human bladder, we will study how the bladder lining is involved in this signaling process, by measuring how bladder chemicals interact with stretch to modulate ATP release, and how ATP can influence nerve impulses to the brain.
Phase III Trial Of Radical Chemo-radiation Vs Radiation Alone In The Management Of Localised Bladder TCC.
Funder
National Health and Medical Research Council
Funding Amount
$194,875.00
Summary
This trial aims to see if the combination of Chemotherapy and Radiation treatment is indeed superior in eradicating the tumor and preserving the Bladder in a greater number of patients as compared to Radiation treatment alone. If the final results from this study do show chemoradiotherapy to be significantly superior to radiation alone, without an increase in morbidity ( especially long term side effects ) , this may lay the platform for a greater proportion of patients with localised bladder ca ....This trial aims to see if the combination of Chemotherapy and Radiation treatment is indeed superior in eradicating the tumor and preserving the Bladder in a greater number of patients as compared to Radiation treatment alone. If the final results from this study do show chemoradiotherapy to be significantly superior to radiation alone, without an increase in morbidity ( especially long term side effects ) , this may lay the platform for a greater proportion of patients with localised bladder cancer, being in the first instance considered for this organ( bladder) preserving approach something which has become a reality at a number of other sites of cancer with the use of multimodality treatment.Read moreRead less
Changes In Pelvic Autonomic Neurons After Spinal Nerve Injury
Funder
National Health and Medical Research Council
Funding Amount
$176,734.00
Summary
This project is about the effects of spinal injury on autonomic neurons that control the bladder, lower bowel and reproductive organs. One of the consequences of some types of spinal injury is that there are no signals being sent from the spinal cord to the nerve cells outside the cord, and this leads to poor bladder control, impotence, etc. We are mimicking this problem experimentally by damaging the spinal nerves that carry these signals. We have found that after this type of damage the pelvic ....This project is about the effects of spinal injury on autonomic neurons that control the bladder, lower bowel and reproductive organs. One of the consequences of some types of spinal injury is that there are no signals being sent from the spinal cord to the nerve cells outside the cord, and this leads to poor bladder control, impotence, etc. We are mimicking this problem experimentally by damaging the spinal nerves that carry these signals. We have found that after this type of damage the pelvic autonomic neurons make many new connections between each other, and the types of new connections depend on which spinal nerves have been injured. This leads to the question: are these new connections good or bad? ie are they helpful in trying to get organ control back to normal or will they stop the correct connections from the spinal cord from being made in the future? This project addresses these questions by using sophisticated techniques for staining and visualising individual nerve fibres growing out from the spinal cord. We will track how well these fibres grow back and connect with the pelvic autonomic neurons. In particular, we will see whether they make correct connections, and if these connections are influenced by the new fibres that have grown between the autonomic neurons in the interim period. We will also do physiological tests to see if the new connections have the correct function. The ultimate aim of these studies is not only to understand more about regeneration, but to see what determines whether the correct connections have been made - and ideally, to give us insight into how we can make regeneration work more quickly and accurately. We believe that this work is an important adjunct to other studies on spinal injury, which mostly focuses on regaining voluntary motor control (e.g. walking); however loss of bladder, bowel and reproductive function is another important quality of life issue for spinal injury patients.Read moreRead less
Pelvic Floor Muscle Training For The Management Of Urinary Incontinence In Elderly Women: A Randomized Controlled Trial.
Funder
National Health and Medical Research Council
Funding Amount
$321,240.00
Summary
Urinary incontinence is associated with significant personal shame and social stigma and affects around 10% of Australians. one-third of women over 60 years of age. Incontinence limits physical activity and this in turn can lead to loss of independence and poorer general health. Fewer than one-third of those with regular incontinence seek assistance. Pelvic floor muscle re-education by physiotherapists is the most commonly recommended method of conservative management for urinary incontinence. P ....Urinary incontinence is associated with significant personal shame and social stigma and affects around 10% of Australians. one-third of women over 60 years of age. Incontinence limits physical activity and this in turn can lead to loss of independence and poorer general health. Fewer than one-third of those with regular incontinence seek assistance. Pelvic floor muscle re-education by physiotherapists is the most commonly recommended method of conservative management for urinary incontinence. Pelvic floor muscle training is safe and effective and should thus be offered as the first choice of treatment for stress urinary incontinence. However there is still no strong evidence for the effectiveness of this intervention in the elderly and because of a perception by medical practitioners that pelvic floor muscle re-education is only effective in younger women, relatively few elderly women are referred to physiotherapy for management of incontinence. Although in clinical practice it is customary to complement pelvic floor muscle training with other forms of conservative management of incontinence such as bladder training, a recent influential study suggested that pelvic floor muscle training and bladder training were equally effective in patients with stress urinary incontinence. It is important to distinguish the relative effectiveness of these interventions used in isolation in order to ensure that urinary incontinence is managed in the most effective and efficient way. This project will therefore investigate the effectiveness of two conservative interventions, pelvic floor muscle training and bladder-behavioural training in women with stress urinary incontinence over 70 years of age. Moreover, strong evidence that conservative intervention is effective for urinary incontinence in the elderly will result in appropriate intervention being offered routinely as the first choice of treatment in older women.Read moreRead less
Sensory Mechanisms In Normal Bladder And In Cystitis
Funder
National Health and Medical Research Council
Funding Amount
$408,861.00
Summary
The function of the lower urinary tract is to store urine and release it at appropriate times. This requires neural circuits in the brain, spinal cord and peripheral ganglia. When the bladder fills, sensory neurones fire and activate these neural circuits to store urine or to empty the bladder. If sensory neurones are too easily excited (a process called sensitisation ) this will lead to clinical disorders, including the common painful bladder syndromes, whose cause is not known (interstitial cy ....The function of the lower urinary tract is to store urine and release it at appropriate times. This requires neural circuits in the brain, spinal cord and peripheral ganglia. When the bladder fills, sensory neurones fire and activate these neural circuits to store urine or to empty the bladder. If sensory neurones are too easily excited (a process called sensitisation ) this will lead to clinical disorders, including the common painful bladder syndromes, whose cause is not known (interstitial cystitis, sensory urgency etc). These are characterised by pelvic pain, urinary urgency, frequency and, in some cases, urge incontinence (loss of urine for no apparent reason) which results from unstable or overactive bladder. Despite a large database of knowledge about the sensory innervation of the bladder, many important gaps still exist. These gaps have restricted the development of new therapies. For example, we have little idea about exactly which functional classes of sensory neurones signal filling of the normal bladder or what different types of information they carry. This is vital information for understanding which neurones are affected in disease states and whether they are all affected in the same way. We have developed new methods that will allow us to identify the major classes of sensory neurones that innervate the bladder, what they respond to and how they are activated. We will also determine whether some classes are preferentially sensitised by inflammation and the most important mechanisms that are likely to underlie this. The significance of this project is that it provides the basic scientific understanding of sensory innervation of the bladder and will identify potential targets for selective pharmacological intervention in common bladder disorders.Read moreRead less
Neurochemicals In The Control Of Human Bladder Function
Funder
National Health and Medical Research Council
Funding Amount
$196,018.00
Summary
The problem of urinary incontinence has received little attention from the medical and scientific research community until the last 10-15 years. Urinary incontinence can cause severe distress and is a taboo subject, even though it affects 30-40% of women. Public figures speak out about their experiences with breast cancer or heart disease, but not about leakage of urine. Elderly people with incontinence are forced into nursing homes, with major costs to the community. Incontinence is a major cli ....The problem of urinary incontinence has received little attention from the medical and scientific research community until the last 10-15 years. Urinary incontinence can cause severe distress and is a taboo subject, even though it affects 30-40% of women. Public figures speak out about their experiences with breast cancer or heart disease, but not about leakage of urine. Elderly people with incontinence are forced into nursing homes, with major costs to the community. Incontinence is a major clinical problem: although over 800 new patients per annum are seen at our Pelvic Floor Unit, the waiting time for a first appointment is 14-15 weeks. There are four main types of urine leakage: - stress incontinence (weak pelvic floor muscles); - overflow incontinence (seen in men with prostatic hypertrophy); - sensory urgency (frequent, uncomfortable desire to urinate); and - detrusor instability (bladder muscle spasms with leakage). We are primarily interested in detrusor instability and sensory urgency, which cause 35% of incontinence in general, but up to 85% of cases in the elderly. Patients suffer from an urgent desire to visit the toilet frequently, and may leak urine if they cannot reach the toilet quickly. Unlike stress incontinence, it cannot be corrected by pelvic floor surgery. Drug treatment is often unsuccessful, with many unacceptable side effects. In our research group, we have found that the sensory nerve which convey the sensation of bladder fullness, are overabundant and display increased amounts of neurochemicals. Our studies in isolated bladder muscle from these patients have shown abnormalities in responsiveness. Thus bladder from women with urge incontinence is resistant to drugs which abolish contraction in normal bladder. In this project we plan to find out why such changes occur. We will use new techniques to study bladder nerves and the receptors which convey the message to contract the bladder muscle.Read moreRead less
A Multi-Centre Feasibility Study Of Online Adaptive Image Guided Radiotherapy For Muscle Invasive Bladder Cancer
Funder
National Health and Medical Research Council
Funding Amount
$580,152.00
Summary
Many studies have shown that the bladder can move, change in size and shape through a course of radiation therapy. As shown in a pilot study, with the online adaptive radiotherapy technique trained staff can daily match the radiation fields to the bladder position and size using a type of CT scan. Potential benefits are better cancer coverage with improved cancer control and less normal tissue irradiation. This study will determine if the technique will work across multiple Australian centres.