Role Of Macrophages In Uropathogenic E. Coli Infections
Funder
National Health and Medical Research Council
Funding Amount
$574,890.00
Summary
Urinary tract infections (UTI) are one of the most common types of infections in humans. They are also a major cause of septic shock, a condition with high fatality rates. Uropathogenic Escherichia coli (UPEC) are the major microbes causing UTI in humans. This project addresses the role of an immune cell type, the macrophage, in UPEC-mediated disease. The outcomes of this project will be a better understanding of how UPEC causes disease, and potentially new treatment regimes for UTI.
Therapeutic Targeting Of Interleukin-22 For Severe Paediatric Urinary Tract Infection And Associated Renal Complications
Funder
National Health and Medical Research Council
Funding Amount
$997,139.00
Summary
Urinary tract infections are among the most common bacterial infections and are associated with the development of chronic kidney disease. The bacteria that cause these infections are becoming increasingly resistant to antibiotic therapy. Therefore, new strategies that target the immune system rather than the bacteria are urgently needed. This study will provide evidence for re-purposing novel immunotherapies targeting the protein interleukin-22 that are being developed for other diseases.
Halting The Spread Multidrug Resistant Uropathogenic E. Coli
Funder
National Health and Medical Research Council
Funding Amount
$687,975.00
Summary
Uropathogenic Escherichia coli (UPEC) is a major cause of urinary tract infection (UTI) and increasingly associated with resistance to multiple antibiotics. This project will study the virulence of multidrug resistant UPEC and use this knowledge to develop new approaches to treat and prevent UTI. The outcomes will be applicable to one of the most common infectious diseases of humans and have broad-reaching impact on our understanding of other infections caused by Gram-negative pathogens.
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 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
Cellular Mechanisms Of Pacemaking In The Upper Urinary Tract: Effects Of Sensory Neuropeptides And Prostaglandins
Funder
National Health and Medical Research Council
Funding Amount
$80,680.00
Summary
The mammalian upper urinary tract (UUT) serves to propel urine from the renal pelvis within the kidney through the ureter to the bladder, where it is stored until micturition. This propulsion of urine from the renal pelvis to the bladder occurs by the means of spontaneous peristaltic contractions in the smooth muscle wall of the UUT, intimately dependent on the localized release of prostaglandins. Approximately 10% of the population suffer from renal calculi (kidney stones) at some stage of thei ....The mammalian upper urinary tract (UUT) serves to propel urine from the renal pelvis within the kidney through the ureter to the bladder, where it is stored until micturition. This propulsion of urine from the renal pelvis to the bladder occurs by the means of spontaneous peristaltic contractions in the smooth muscle wall of the UUT, intimately dependent on the localized release of prostaglandins. Approximately 10% of the population suffer from renal calculi (kidney stones) at some stage of their lifetime, with men being 2-4 times more likely than women to have calculi. Pain management of renal colic usually involves the prescribing of strong analgesics, and antispasmodic and nonsteroidal anti-inflammatory agents. Most stones are expelled spontaneously if they are small. Larger stones require interventions such as fragmentation (extracorpereal lithotripsy), which is an out patient procedure, or physical removal, using ureterscopes or endoscopes or open surgery under general anesthesia; procedures usually requiring hospital stays of 2-7 days. This project will provide valuable information on the mechanisms by which sensory nerves and endogenous prostaglandins control motility in the mammalian UUT. In particular, these studies will contribute to the search of specific anti-inflammatory agents which will affect particular aspects of UUT motility. A clearer understanding of the cellular origin of UUT rhythmicity will lead to more informed non-surgical interventions to encourage the passing of painful calculi. Such information will also aid in the treatments of other forms of renal colic, during ureteric obstruction, and urinary tract infection. Ureteric stasis is an important condition to avoid, if left untreated permanent kidney damage usually occurs within 6 weeks.Read moreRead less