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Understanding The Role Of Infectious Agents As A Trigger Of Crohns Disease In Children With Early Onset Disease
Funder
National Health and Medical Research Council
Funding Amount
$570,876.00
Summary
Crohn's disease is a major cause of illness throughout the world. There is no cure and current therapies carry substantial risks. An infectious agent has been suggested as the trigger for disease but research has been inconclusive. Our study focuses on the characterisation of a novel virus we have identified that may trigger Crohn's disease in children at disease onset.
Exploring The Mechanisms Of Generation Of Intestinal TH17 Responses And The Mechanisms Of TH17 Mediated Pathology
Funder
National Health and Medical Research Council
Funding Amount
$617,531.00
Summary
Our research recently described a mouse that shows excellent similarities to human inflammatory bowel diseases. We further show that the disease mediating substances called cytokines are also similar between our mouse and UC. Particularly, a recently described network of cytokines that are the major mediators of disease in our mice and human IBD. This project examines how we can best interfere with the actions of these cytokines to treat and prevent intestinal inflammation.
Epithelial cell surface mucins are large complex proteins found on the surface of all mucosal epithelial tissues, for example in the respiratory, gastrointestinal, reproductive and urinary tracts. Most bacterial and viral pathogens enter the body via mucosal tissues. We have recently demonstrated that mucin proteins are a vital component of initial defence against mucosal pathogens. Defects in these proteins probably predispose individuals to common chronic infective and inflammatory diseases. T ....Epithelial cell surface mucins are large complex proteins found on the surface of all mucosal epithelial tissues, for example in the respiratory, gastrointestinal, reproductive and urinary tracts. Most bacterial and viral pathogens enter the body via mucosal tissues. We have recently demonstrated that mucin proteins are a vital component of initial defence against mucosal pathogens. Defects in these proteins probably predispose individuals to common chronic infective and inflammatory diseases. The proposed research aims to explore the mechanims by which mucins protect from infection, with a focus on the gastrointestinal tract. Gastrointestinal infections remain one of the major causes of mortality in children in undeveloped countries. We believe that these proteins are a critical hereto unrecognised element of immunity and that the proposed studies will have broad significance for treatment and prevention of infection. Additionally, understanding the function of mucins could lead to the development of new drugs to treat epithelial inflammation such as that seen in inflammatory bowel diseases and respiratory diseases such as asthma and cystic fibrosis.Read moreRead less
Transcutaneous Electrical Stimulation To Relieve Chronic Constipation In Children
Funder
National Health and Medical Research Council
Funding Amount
$346,995.00
Summary
We have over 300 children with chronic treatment-resistant constipation at Royal Children's Hospital Melbourne. We have a new physiotherapy technique that may overcome constipation and stop soiling in many of these children. In 2003-4, we ran a pilot study to test a technique used by physiotherapists to treat urinary incontinence. We have called the method TESIC (transcutaneous electrical stimulation using interferential current). TESIC uses suction electrodes placed on the belly and back at the ....We have over 300 children with chronic treatment-resistant constipation at Royal Children's Hospital Melbourne. We have a new physiotherapy technique that may overcome constipation and stop soiling in many of these children. In 2003-4, we ran a pilot study to test a technique used by physiotherapists to treat urinary incontinence. We have called the method TESIC (transcutaneous electrical stimulation using interferential current). TESIC uses suction electrodes placed on the belly and back at the level of the belly button. The electrical stimulation is applied using a current (interferential current) that stimulates deep into the abdomen. We tested 8 children and had very encouraging results with improved constipatio in 5-8 and all with soiling stopped. Parents and children are keen to use this technique but first we need to establish that the results are reproducible in a larger group of 70 children. We also need to know if the effect was just a placebo response (due to time spent with the physiotherapists), and how long the effect lasts. We will also measure changes in soiling. Faecal soiling is smelly and antisocial. Relief of soiling has a big impact on a child's ability to fit in at school and to attend normal schooling. We will measure outcomes using daily diaries kept by children, questionnaires, how quickly food moves through the bowel and pressures within the bowel. We have a multidiciplinary team of experienced clinicians and scientists with expertise in these techniques and in constipation and incontinence in children (paediatric surgeon, gastroenterologist, manometry nurse, incontinence paediatrician and physiotherapist, expert in electrical stimulation and gut nervous system scientist). This technique could revolutionise treatment of chronic constipation. Most physiotherapists have TESIC machines, allowing delivery Australia wide. It is non-invasive and should also be able to be used by adults, including the elderly in nursing homes.Read moreRead less
Monocytes/macrophages In Chronic Liver Diseases: Cross-talk With Hepatocytes And Nonparenchymal Cells And Role In Progressive Liver Injury
Funder
National Health and Medical Research Council
Funding Amount
$598,645.00
Summary
More than 170 million people world-wide are chronically infected with the hepatitis C virus. Approximately 10-15% of chronically infected subjects develop cirrhosis with its attendant risks of liver failure and hepatocellular carcinoma. The objective of this important project is to examine the mechanisms by which monocytes and macrophages (cells of the immune system) enhance or impair the progression of liver disease and response to antiviral treatment in patients with chronic hepatitis C.
Clinical And Microbiological Predictors Of Post-operative Crohn's Disease Recurrence
Funder
National Health and Medical Research Council
Funding Amount
$120,253.00
Summary
The multi-centre randomised controlled POCER (Post-Operative Crohn’s Disease Recurrence) trial has shown that following “curative” surgery, the anti-tumour necrosis factor drug adalimumab prevents recurrent disease in almost all patients. I will examine the multiple factors that contribute to disease recurrence including assessment of mucosal microbiota, faecal biomarkers and serological antibody markers in patients with Crohn's disease. Results will improve clinical outcomes and change internat ....The multi-centre randomised controlled POCER (Post-Operative Crohn’s Disease Recurrence) trial has shown that following “curative” surgery, the anti-tumour necrosis factor drug adalimumab prevents recurrent disease in almost all patients. I will examine the multiple factors that contribute to disease recurrence including assessment of mucosal microbiota, faecal biomarkers and serological antibody markers in patients with Crohn's disease. Results will improve clinical outcomes and change international practice.Read moreRead less
Clinical And Microbiological Studies Of Faecal Microbiota Transplantation In Ulcerative Colitis - A Phase II, Multicentre, Randomised Double Blind, Exploratory Proof Of Concept, Placebo Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$140,949.00
Summary
Ulcerative Colitis (UC) is a chronic inflammatory condition affecting the large bowel. It is the result of a dysfunctional immune system that inappropriately targets and damages the colon. There is increasing evidence that gut bacteria play a crucial role in UC, possibly by stimulating inappropriate activation of immune cells. We believe that by "transplanting" the faeces (and thus gut microbes) of healthy individuals into the colon of UC patients, we may change the bacterial make up and correct ....Ulcerative Colitis (UC) is a chronic inflammatory condition affecting the large bowel. It is the result of a dysfunctional immune system that inappropriately targets and damages the colon. There is increasing evidence that gut bacteria play a crucial role in UC, possibly by stimulating inappropriate activation of immune cells. We believe that by "transplanting" the faeces (and thus gut microbes) of healthy individuals into the colon of UC patients, we may change the bacterial make up and correct the inappropriate immune system activation.Read moreRead less
The Epidemiology And Burden Of Liver Disease In Australia With An Emphasis On Non-alcoholic Fatty Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$151,143.00
Summary
Non alcoholic fatty liver disease is now the commonest cause of abnormal liver function in Australia due to its close association with the obesity epidemic. It is likely to become the leading cause of liver failure and liver cancer over the next few decades. Despite this, the prevalence in Australian populations is unknown. The aim of this project is to assess how common this disorder is, the burden it places on the healthcare system and the effectiveness of treatment for liver cancer caused by ....Non alcoholic fatty liver disease is now the commonest cause of abnormal liver function in Australia due to its close association with the obesity epidemic. It is likely to become the leading cause of liver failure and liver cancer over the next few decades. Despite this, the prevalence in Australian populations is unknown. The aim of this project is to assess how common this disorder is, the burden it places on the healthcare system and the effectiveness of treatment for liver cancer caused by advanced non alcoholic fatty liver disease.Read moreRead less
Development Of Serum Models That Can Predict Clinical Outcomes In Chronic Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$380,694.00
Summary
The overall objective of this project is to develop blood tests that can accurately predict liver related death, liver cancer and liver decompensation respectively for patients with chronic liver disease. Blood tests will also be developed to predict cardiovascular disease in patients with non-alcoholic fatty liver disease. Furthermore, we will evaluate the use of repeated blood tests to assess if this can more accurately predict death and complications compared to a single time point.