Pathophysiology And Treatment Of Pharyngo-oesophageal Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$168,275.00
Summary
A number of oral and respiratory tract diseases such as laryngitis, asthma, unexplained cough, sinusitis, and obstructive sleep apnoea, have been linked with gastroesophageal reflux disease. These particular respiratory complications carry significant morbidity and mortality. The mechanisms of regurgitation of gastric acid, via the oesophagus into the pharynx, are unknown. We have recently validated a novel technique to reliably detect acid regurgitation events into the pharynx. We propose to us ....A number of oral and respiratory tract diseases such as laryngitis, asthma, unexplained cough, sinusitis, and obstructive sleep apnoea, have been linked with gastroesophageal reflux disease. These particular respiratory complications carry significant morbidity and mortality. The mechanisms of regurgitation of gastric acid, via the oesophagus into the pharynx, are unknown. We have recently validated a novel technique to reliably detect acid regurgitation events into the pharynx. We propose to use this technique, combined with pressure recordings from the oesophagus and its valves, to determine the precise mechanisms underlying acid regurgitation into the throat. Such studies should lead to better means of treating these disorders.Read moreRead less
ASSESSMENT OF ENDOPLASMIC RETICULUM STRESS AND MUTATIONS IN MUCIN OLIGOMERIZATION DOMAINS IN ULCERATIVE COLITIS
Funder
National Health and Medical Research Council
Funding Amount
$292,216.00
Summary
Ulcerative colitis affects 0.2% of Australians causing chronic or recurrent health morbidity and affecting employment. In severe cases it is life threatening. Its pathogenesis remains poorly understood. We have exciting and novel preliminary data from humans and informed by our unique animal models that make us propose that the disease is caused by Endoplasmic Reticulum Stress due to misfolding of mucin. We have designed fully powered prospective clinical and lab studies to test this hypothesis.
Motor Patterns Of Colonic Transit And Pathophysiology Of Severe Constipation.
Funder
National Health and Medical Research Council
Funding Amount
$196,018.00
Summary
This project aims to clarify the contractile patterns of the human colon which underlie the very common and distressing condition of constipation. We will be relating symptoms of constipation from a large number of sufferers with actual measurements of contractions and flow of content along the colon in these patients. The aim will be to try and identify abnormal patterns responsible for the constipation so that future studies can target appropriate drugs at the responsible defect. A better unde ....This project aims to clarify the contractile patterns of the human colon which underlie the very common and distressing condition of constipation. We will be relating symptoms of constipation from a large number of sufferers with actual measurements of contractions and flow of content along the colon in these patients. The aim will be to try and identify abnormal patterns responsible for the constipation so that future studies can target appropriate drugs at the responsible defect. A better understanding of clusters or symptoms and how they might predict such underlying abnormalities is crucial for the safer and more cost effective diagnosis and treatment of affected patients. Pharmacological studies in the human as well as on tissue obtained from affected patients at surgery will be conducted to better understand the presumptive abnormalities affecting the nerves within the colon in constipation.Read moreRead less
Impact Of Oesophageal Afferent Processing On Regulatory And Protective Reflexes, And Perception Of Symptoms
Funder
National Health and Medical Research Council
Funding Amount
$247,500.00
Summary
Symptoms of acid reflux, heartburn and regurgitation, are extremely common, occurring weekly in 20% of the population. Curiously, about 1-4 of people with heartburn don't have any more acid exposing their oesophagus than do normal people. We do not understand this apparent increased sensitivity. Many patients with reflux present with cough, asthma, hoarseness, sore throat or even lung fibrosis. Regurgitation of acid causes some of these conditions. It is estimated that 60% of adult asthmatics ha ....Symptoms of acid reflux, heartburn and regurgitation, are extremely common, occurring weekly in 20% of the population. Curiously, about 1-4 of people with heartburn don't have any more acid exposing their oesophagus than do normal people. We do not understand this apparent increased sensitivity. Many patients with reflux present with cough, asthma, hoarseness, sore throat or even lung fibrosis. Regurgitation of acid causes some of these conditions. It is estimated that 60% of adult asthmatics have reflux for example. The purpose of this research is to examine the notion that the sensory nerves coming from the oesophagus are somehow tuned up to fire off too readily. If true this phenomenon may well underlie the inappropriate relaxation of the oesophageal valve mechanisms that normally prevent acid flowing up into the throat and into the airways. Additionally it may explain why so many sufferers seem to be hypersensitive to even small amounts of acid. These studies will better define the nerve pathways involved in heartburn and regurgitation and help us target these diseases with specific drugs in the future.Read moreRead less
Spatio-temporal Analysis Of Rat Intestinal Motility In Physiological And Disease Models
Funder
National Health and Medical Research Council
Funding Amount
$358,750.00
Summary
This project addresses the question of how the movements of the gut are controlled in health and disease. The progress of food along the gut is due to movements of the involuntary muscle of the wall of the intestine. Three fundamental mechanisms are involved. One is the spontaneous ability of the intestinal muscle to contract rhythmically and is driven by a delicate net of pacemaker cells. Fast propulsion of food contents depends on nerve circuits in the gut wall that generate a powerful pumping ....This project addresses the question of how the movements of the gut are controlled in health and disease. The progress of food along the gut is due to movements of the involuntary muscle of the wall of the intestine. Three fundamental mechanisms are involved. One is the spontaneous ability of the intestinal muscle to contract rhythmically and is driven by a delicate net of pacemaker cells. Fast propulsion of food contents depends on nerve circuits in the gut wall that generate a powerful pumping behaviour to prevent over-filling or to eject toxic or irritating substances (eg: some laxatives activate this mechanisms). This is often called peristalsis. A third mechanism consists of activity of nerve cells in the gut, that slowly propagates along the intestine and causes the muscle to contract, sweeping along any remnants. The movements generated by these three mechanisms occur in segments of intestine isolated from rats. The major difficulty up until now has been to relate the actual movements in living animals to these fundamental mechanisms. It is now possible to bridge this gap because we have developed methods to record, display and measure graphically the actual movements. Movements are transformed into spatio-temporal maps which show all of the contractions over a period of time. Coordinated activity is visible in these maps as recognisable patterns or visual objects. Measurements can be readily made with conventional statistics. The literature in gastroenterology is full of descriptions of motility based on indirect methods of recordings. In this project we will be able to correlate the previous indirect methods with the new graphic methods and thus establish a clearer, simpler and more accurate classification of normal patterns of intestinal motility. We will then use this to establish what goes wrong in a number of experimental diseases known to affect adversely the movements of the intestine.Read moreRead less