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
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.
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
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.
Urinary Tract E. Coli: The Good Guys Versus The Bad Guys
Funder
National Health and Medical Research Council
Funding Amount
$296,150.00
Summary
Escherichia coli is the primary cause of urinary tract infection (UTI) in the developed world. In Australia alone, E. coli affects more than 250,000 yearly to the extent where they require medical intervention. It is estimated that one in four women and one in twenty men will develop a UTI in their lifetime and in the USA UTIs result in $1.6 billion in medical expenses each year. Uropathogenic E. coli (UPEC) strains readily form biofilms on indwelling catheters and recent evidence suggests that ....Escherichia coli is the primary cause of urinary tract infection (UTI) in the developed world. In Australia alone, E. coli affects more than 250,000 yearly to the extent where they require medical intervention. It is estimated that one in four women and one in twenty men will develop a UTI in their lifetime and in the USA UTIs result in $1.6 billion in medical expenses each year. Uropathogenic E. coli (UPEC) strains readily form biofilms on indwelling catheters and recent evidence suggests that they also form biofilm-like aggregates in the bladder. No treatment other than antibiotics (often inefficient due to resistance) is currently available. E. coli is also the most frequent cause of asymptomatic bacteriuria (ABU). ABU occurs in up to 6% of healthy individuals and affects high risk groups such as the elderly and diabetics. In general, most patients with ABU do not need treatment and in many cases the colonizing organism actually helps to prevent infection by other more virulent bacteria. The aim of this project is to compare UPEC and ABU E. coli for differences associated with virulence and biofilm growth. The project will generate a comprehensive and defined strain bank relative to E. coli that cause UTI. Understanding biofilm growth by this organism may lead to the development of improved and-or novel treatments. Furthermore, increased knowledge of ABU E. coli is essential if we are to fully explore the possibility of employing these organisms as probiotic agents to prevent infection by other pathogens in specific high risk patient groups.Read moreRead less
Plasticity And Regeneration Of Bladder Motor Nerve Circuits After Injury
Funder
National Health and Medical Research Council
Funding Amount
$333,313.00
Summary
Our goal is to determine ways of improving the recovery of bladder-controlling nerves after they are injured, which has devastating effects on bladder function. This can happen because of lumbosacral spinal nerve damage or pelvic surgery. We also expect to establish broad principles that may be tested in other neurological conditions that affect bladder function, such as neurodegenerative disorders (e.g. diabetes) and spinal cord injury.
Probiotic Prophylaxis Of Spinal Cord Injury Urinary Tract-Infection TherapeUtic-Trial (ProSCIUTTU)
Funder
National Health and Medical Research Council
Funding Amount
$800,747.00
Summary
Urinary Tract Infections (UTI) are common in spinal cord injury (SCI) and about 2-year occur in SCI. Antibiotic resistance is also common in SCI. UTI are harder to treat with high rates of antibiotic resistance and this often leads to hospitalisation with significant health and economic consequences to the SCI community and country. Probiotics may prevent UTI and treat people colonised with resistant organisms. Unlike alternatives like antibiotics, they do not worsen antibiotic resistance.
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
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