The University of Western Sydney’s new School of Medicine (SoMed) had its first intake of students in 2007, with the aim of producing doctors for practice in Western Sydney. From the outset, the plan was to become a community engaged... more
The University of Western Sydney’s new School of Medicine (SoMed) had its first intake of students in 2007, with the aim of producing doctors for practice in Western Sydney. From the outset, the plan was to become a community engaged medical school, with a commitment that this be demonstrated by graduates, students and staff. So what do we mean by engaged, and how can we measure our success in achieving it? This paper provides a case study on the development of an engaged teaching and learning program. We begin with an examination of the philosophies the SoMed has drawn on. Then, by isolating those aspects which have influenced our directions, evaluate specific components to measure success and to identify areas needing further development. Two paths converged in the creation of our engaged medical school. One path can be located specifically within the field of medicine. The second is that influencing the world of universities more broadly. The two paths share characteristics, but there are also unique features of medicine influencing the shape of community engagement in this profession. By drawing the two together we believe both are enriched.
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University of Western Sydney's new School of Medicine (SoMed) had its first intake of students in 2007, with the aim of producing doctors for practice in Western Sydney. From the outset, the plan was to become a community engaged... more
University of Western Sydney's new School of Medicine (SoMed) had its first intake of students in 2007, with the aim of producing doctors for practice in Western Sydney. From the outset, the plan was to become a community engaged medical school, with a commitment that this be demonstrated by graduates, students and staff. So what do we mean by engaged, and how can we measure our success in achieving it? This paper provides a case study on the development of an engaged teaching and learning program. We begin with an examination of the philosophies the SoMed has drawn on. Then, by isolating those aspects which have influenced our directions, evaluate specific components to measure success and to identify areas needing further development. Two paths converged in the creation of our engaged medical school. One path can be located specifically within the field of medicine. The second is that influencing the world of universities more broadly. The two paths share characteristics, but there are also unique features of medicine influencing the shape of community engagement in this profession. By drawing the two together we believe both are enriched.
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Research Interests: Primary Care, Immunology, Gastroenterology, Medicine, Humans, and 15 moreInternal Medicine, Placebo, Female, Male, Arthritis, Clinical Sciences, Aged, Middle Aged, Adult, Public health systems and services research, Adverse Event, Esomeprazole, Life Table, Confidence Interval, and Gastrointestinal Diseases
Human intestinal trefoil factor (ITF), a mucosa-associated trefoil peptide, has been implicated in maintenance of mucosal integrity and may denote commitment to goblet cell differentiation. We have quantitated and localized ITF expression... more
Human intestinal trefoil factor (ITF), a mucosa-associated trefoil peptide, has been implicated in maintenance of mucosal integrity and may denote commitment to goblet cell differentiation. We have quantitated and localized ITF expression in normal and neoplastic colons, determined the molecular forms present, and examined the relationships among ITF expression and mucin production and increasing dysplasia. Normal and neoplastic human colonic mucosa (n = 30) were extracted for quantitation by ITF radioimmunoassay and size determination by gel filtration and immunoblotting. Paraffin sections of normal bowel, hyperplastic polyps, adenomatous polyps, and adenocarcinoma were examined for ITF immunohistochemistry and mucin histochemistry. The predominant molecular species in both normal and neoplastic colon was a 7-kd monomer. Staining was localized to goblet and Paneth cells and the luminal surface in normal colon and in most adenomatous polyps but not hyperplastic polyps; this colocalized with periodic acid-Schiff histochemistry. ITF staining of undifferentiated cells was seen with increasing dysplasia, and Golgi region immunoreactivity was highly conserved in adenocarcinoma, independent of the presence of periodic acid-Schiff-positive mucin. ITF concentration in colonic extracts was 10 to 200 pmol/g. Levels in normal (88.1 +/- 15.1 pmol/g) and malignant (90.1 +/- 12.7 pmol/g) tissue were comparable. In carcinomas, there were significant associations among ITF expression and degree of differentiation and mucin presence. Loss of expression was associated with tumor necrosis and advanced Duke's stage. ITF is uniformly processed in normal and neoplastic colons. Goblet cell-derived ITF is associated with stainable mucin production. ITF synthesis by non-goblet colonocytes, however, is highly conserved in neoplastic differentiation.
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Research Interests: Gastroenterology, Medicine, British medical history, Humans, Internal Medicine, and 15 moreSmoking, Female, Male, Aged, Middle Aged, Adult, Public health systems and services research, Adverse Drug Reaction, BMJ, Benzimidazoles, Duodenal Ulcer, Random Allocation, Clinical Trials as Topic, Adverse effect, and Omeprazole
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Adaptation of the gastric mucosa to nonsteroidal anti-inflammatory drug-induced injury is a well-documented phenomenon, but the mechanisms are not known. We investigated whether changes in stress protein expression and apoptosis play... more
Adaptation of the gastric mucosa to nonsteroidal anti-inflammatory drug-induced injury is a well-documented phenomenon, but the mechanisms are not known. We investigated whether changes in stress protein expression and apoptosis play roles in ...
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Research Interests: Cardiology, Design, Randomization, Evaluation, Treatment Outcome, and 16 moreComparative Study, Safety, Conception, Prospective studies, Complication, Humans, Toxicity, Follow-up studies, Arthritis, Ibuprofen, Middle Aged, Public health systems and services research, Cardiovascular Diseases, End, Pyrazoles, and Naproxen
... Arch. Anat. Microsc. Morphol. Exp. 61, 17-32. Gas, N., and Noaillac-Depeyre, J. (1978). Types cellulaires de l'estomac, assurant la production du suc gastrique, chez Ameirus nebulosus L. Biol. Cell. 31, 181-90. Giraud, AS,... more
... Arch. Anat. Microsc. Morphol. Exp. 61, 17-32. Gas, N., and Noaillac-Depeyre, J. (1978). Types cellulaires de l'estomac, assurant la production du suc gastrique, chez Ameirus nebulosus L. Biol. Cell. 31, 181-90. Giraud, AS, Yeomans, ND, and St John, DJB (1979). ...
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OBJECTIVE: To discuss some of the critical issues in the pathophysiology and management of peptic ulcer disease.OPINION: Peptic ulcer disease has multiple causes, although gastric acid has traditionally been considered the primary... more
OBJECTIVE: To discuss some of the critical issues in the pathophysiology and management of peptic ulcer disease.OPINION: Peptic ulcer disease has multiple causes, although gastric acid has traditionally been considered the primary aggressive factor. Helicobacter pylori infection is established as a major causative factor, but some aspects of the mechanisms by which H. pylori causes peptic ulceration remain unclear. Treatment with proton pump inhibitors (PPIs) is the most effective means of healing peptic ulcers. In addition to healing a higher proportion of ulcers than H2-receptor antagonists, PPIs provide faster healing and relief of symptoms. The ability of PPIs to produce effective and sustained inhibition of gastric acid secretion suggests that they may also become the treatment of choice for gastric ulcers caused by non-steroidal anti-inflammatory drugs. However, eradication of H. pylori infection is more effective than maintenance therapy with antisecretory agents in reducing the rate of recurrence of peptic ulcers initially healed using antisecretory therapy. H. pylori eradication is therefore the optimal, and almost certainly the most cost-effective, approach to the long-term management of patients with peptic ulcer disease. Despite the fact that 90-95% of patients with demonstrable duodenal ulceration are probably infected with H. pylori, it is recommended that, in routine clinical practice, infection is diagnosed before eradication therapy is instituted. H. pylori testing 4-6 weeks after the completion of eradication therapy is also recommended to check that the infection has been successfully cured. For routine clinical practice, the highly sensitive and specific rapid urease test is probably the most useful diagnostic approach. The most appropriate H. pylori eradication regimen remains to be defined. However, 1-2 weeks of treatment with a combination of a PPI and two antimicrobial agents achieves eradication rates in excess of 90%, which are similar to those attained using standard triple therapy, but with the advantage of better patient compliance and greater tolerability. Preliminary evidence also suggests that H. pylori eradication prevents the recurrence of peptic ulcer bleeding, although further studies are required.CONCLUSION: H. pylori eradication by 1-2 weeks' treatment with a combination of a PPI and two antimicrobial agents appears to be the optimal (and probably the most cost-effective) approach to the long-term management of patients with peptic ulcer disease, and represents a major advance in the management of such patients.
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Research Interests: Gastroenterology, Australia, Electrocardiography, Prospective studies, Humans, and 17 moreFemale, Male, Risk factors, Creatine Kinase, Clinical Sciences, GASTROENTEROLOGY AND HEPATOLOGY., Aged, Middle Aged, Digestive System, Adult, Biological markers, Risk Factors, Troponin, Troponin I, Prospective Study, Predictive value of tests, and Heart Diseases
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To compare the impact on quality of life (QoL) of omeprazole and misoprostol during healing, and omeprazole, misoprostol, and placebo during maintenance treatment in chronic NSAID users with NSAID-associated gastroduodenal lesions.... more
To compare the impact on quality of life (QoL) of omeprazole and misoprostol during healing, and omeprazole, misoprostol, and placebo during maintenance treatment in chronic NSAID users with NSAID-associated gastroduodenal lesions. Validated baseline and follow-up QoL questionnaires were completed by 610 patients (healing: after 4/8 weeks; maintenance: after 6 months). Patients with arthritis being treated with NSAIDs have a poor QoL. Rheumatoid arthritis causes more joint problems and physical mobility limitations than osteoarthritis. Chronic NSAID use causes heartburn and dyspepsia. QoL improved on both treatments (about equally on two general QOL scales), but omeprazole relieved gastrointestinal symptoms more than misoprostol, particularly reflux, abdominal pain and indigestion symptoms. During maintenance, both treatments maintained QoL, but misoprostol induced diarrhoea. QoL in arthritis patients on chronic NSAID treatment is destroyed. Omeprazole is superior to misoprostol for relief and prevention of NSAID-associated gastrointestinal symptoms allowing continued NSAID treatment without compromising the patients' QoL.
Research Interests: Long Term Care, Quality of life, Evaluation, Treatment, Rheumatoid Arthritis, and 19 moreRisk assessment, Adolescent, Comparative Study, Probability, Psychological Well Being, Norway, Humans, Toxicity, Female, Male, Clinical Sciences, Aged, Middle Aged, MISOPROSTOL, Adult, Analysis of Variance, Risk Assessment, Reference Values, and Cohort Studies
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Research Interests: Regeneration, Immunohistochemistry, Gene expression, Biopsy, Antibodies, and 21 moreCell Differentiation, Neuropeptides, Humans, Animals, Gastric Cancer, Male, Peptides, Proteins, Laboratory, Clinical Sciences, Rats, Transforming Growth Factor Beta, Wistar Rats, Substance P, Acetic Acid, Rabbits, Gastritis, Mucins, Radioimmunoassay, Adenocarcinoma, and Transforming Growth Factor
Rats were rendered iron deficient by a combination of diet and bleeding to study its effects on vitamin B(12) absorption. Small intestinal loops were isolated in vivo and the absorption of -57Co-vitamin B(12) bound to a known quantity of... more
Rats were rendered iron deficient by a combination of diet and bleeding to study its effects on vitamin B(12) absorption. Small intestinal loops were isolated in vivo and the absorption of -57Co-vitamin B(12) bound to a known quantity of intrinsic factor was measured. Iron deficiency resulted in the impairment of both uptake and transport of B(12). This malabsorption was corrected within 5 days by parenteral iron repletion. The findings were not due to a non-specific effect of anaemia since no correlation existed between haemoglobin levels and B(12) absorption in rats anaemic as a result of acute blood loss. No evidence was found for an altered small-intestinal microflora, bacterial counts being similar in iron-deficient and control rats. It is concluded that iron deficiency in the rat results in impaired absorption of B(12) by the small intestine, probably as a result of some defect produced in the enterocyte.
Research Interests: Pathology, Kidney, Liver, Female, Animals, and 4 moreBacteria, Clinical Sciences, Intestinal absorption, and Rats
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The associations between nonsteroidal anti-inflammatory drugs (NSAIDs) and the presence and complications of gastroduodenal erosions and ulcers are well established. Evidence that acid aggravates NSAID-induced injury provides a rationale... more
The associations between nonsteroidal anti-inflammatory drugs (NSAIDs) and the presence and complications of gastroduodenal erosions and ulcers are well established. Evidence that acid aggravates NSAID-induced injury provides a rationale for minimising such damage by acid suppression. Other strategies discussed include avoidance of NSAIDs or minimising their dosage, selecting NSAIDs known to cause less damage, and co-prescription of various agents. Cytoprotection with misoprostol, a prostaglandin analogue, has been shown to be effective in reducing NSAID-related peptic ulcers and their complications. Unfortunately, adverse effects may limit compliance in some patients. Histamine H2 antagonists have only limited efficacy in the prevention of NSAID-induced ulcers in humans, particularly in the stomach, except at higher than standard dosages. This may relate to their relatively modest effect in elevating gastric pH, especially in comparison with proton pump inhibitors. Several studies now confirm the efficacy of proton pump inhibitors in the short and longer term prevention of NSAID-induced upper gastrointestinal injury. Placebo-controlled studies suggest reductions of over 70% in gastric and duodenal ulcer rates over 3 to 6 months. The recent ASTRONAUT (Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-Associated Ulcer Treatment) study documented the greater prophylactic efficacy of omeprazole over ranitidine at standard dosages for 6 months. The OMNIUM (Omeprazole versus Misoprostol for NSAID-Induced Ulcer Management) study showed omeprazole to be slightly more effective overall than misoprostol in preventing the upper gastrointestinal adverse effects of NSAIDs, with both substantially more effective than placebo, although misoprostol was somewhat less well tolerated. Although substantial reductions in NSAID ulceration are now achievable when co-therapy with a proton pump inhibitor is given, a few patients will still develop ulcers and their complications. Hence the judicious use of NSAIDs in the first instance cannot be overemphasised.
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We review papers on nonsteroidal antiinflammatory drugs (NSAID) and the stomach published in the 12 months ending April 2002. During this period, some further developments occurred in the ongoing search for safer antiinflammatory drugs.... more
We review papers on nonsteroidal antiinflammatory drugs (NSAID) and the stomach published in the 12 months ending April 2002. During this period, some further developments occurred in the ongoing search for safer antiinflammatory drugs. The highly selective COX-2 inhibitors (COX-2i) have again exhibited some toxicity in animal models of repair, but continue to seem a safer alternative than nonselective inhibitors from the standpoint of the production of human ulcers. Some data on the gastrointestinal safety of valdecoxib and parecoxib are available, while co-therapies with acid suppressants to reduce the risk of conventional NSAID also remain an option (a study comparing lansoprazole with misoprostol is now published). Whether co-prescribing a proton pump inhibitor with a COX-2i in patients at higher risk is effective or justified awaits the results of yet to be completed studies. The nitric oxide (NO)-donating NSAID and NO-donating aspirin show some distinct promise in animal studies and early-phase clinical trials.
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The proton-secreting parietal cell is shown, from recent evidence, to be the principal focus for the actions of aspirin (and related drugs) in damaging the gastric mucosa. It is suggested that the selective damage to the parietal cells is... more
The proton-secreting parietal cell is shown, from recent evidence, to be the principal focus for the actions of aspirin (and related drugs) in damaging the gastric mucosa. It is suggested that the selective damage to the parietal cells is due to the ph gradient favouring a high rate of aspirin uptake and subsequent entrapment of drug anions inside these cells. This concept may serve as a useful basis for developing procedures to minimize the gastric damage by aspirin and related acidic drugs.
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Stomachs of 22 rats treated with aspirin for six months were examined histologically at times ranging from 6 to 18 months after completion of treatment. Healed chronic gastric ulcers were found in 20 rats. Glandular dysplasia was present... more
Stomachs of 22 rats treated with aspirin for six months were examined histologically at times ranging from 6 to 18 months after completion of treatment. Healed chronic gastric ulcers were found in 20 rats. Glandular dysplasia was present at the sites of healed ulcers in 12 rats, the glands extending into the submucosa, muscularis propria, and even subserosal fat. The apparent lack of progression with time and the absence of metastases suggest that the changes are not neoplastic but are a consequence of repeated injury and regeneration, with entrapment of glands below the level of the muscularis mucosae. The lesions in the aspirin-treated animals closely resemble those of gastritis cystica polyposa and colitis cystica profunda in the human subject.
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A sensitive and specific high pressure liquid chromatographic procedure for ranitidine estimation is described and pharmacokinetic studies in six healthy volunteers reported. Each subjects received 20 mg of ranitidine i.v.; 20 mg, 40 mg... more
A sensitive and specific high pressure liquid chromatographic procedure for ranitidine estimation is described and pharmacokinetic studies in six healthy volunteers reported. Each subjects received 20 mg of ranitidine i.v.; 20 mg, 40 mg and 100 mg orally having fasted overnight and 100 mg with a standard meal. Following the i.v. dose, ranitidine plasma concentrations fell biexponentially with a distribution half-life of 6.1 +/- 0.9 min and a terminal elimination half-life of 1.9 +/- 0.1 h. The volume of distribution was 115 +/- 7 1 and the systemic plasma clearance 709 +/- 62 ml/min. After 20 mg oral doses the systemic availability was high (88 +/- 10%). Bioavailability was unaffected by food and AUC increased linearly with dose to 100 mg. Renal excretion of unchanged ranitidine was between 50 and 70% and a further 1-3% was excreted as desmethylranitidine. In separate studies, the inhibitory action of cimetidine and ranitidine on pentagastrin stimulated gastric acid output was compared in seven duodenal ulcer patients. Results so far indicate that ranitidine 150 mg i.v. produces a more pronounced and more prolonged suppression of pentagastrin stimulated gastric acid output than cimetidine 200 mg i.v. (p less than 0.001). Ranitidine produced a sustained near total (greater than 90%) suppression in acid output in the period 60 to 120 min after drug administration, whereas acid output with cimetidine was less and fell from 82 to 54% in the same period.
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Research Interests: Humans, Liver, Female, Male, Middle Aged, and 7 moreAdult, Time Factors, Guanidines, Ranitidine, Furans, Cimetidine, and Duodenal Ulcer
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Epidemiological evidence consistently indicates that aspirin or non-aspirin non-steroidal anti-inflammatory drug use is associated with the occurrence of gastric ulceration, gastric and ulcer bleeding, and ulcer death. Evidence on... more
Epidemiological evidence consistently indicates that aspirin or non-aspirin non-steroidal anti-inflammatory drug use is associated with the occurrence of gastric ulceration, gastric and ulcer bleeding, and ulcer death. Evidence on duodenal ulcer occurrence conflicts, possibly because of differences in study populations. A wide range of mechanisms could explain the occurrence of non steroidal-induced damage. These include inhibition of bicarbonate secretion, effects on mucus formation, and vascular actions. Not all effects are dependent on cyclo-oxygenase inhibition. Short-term studies in humans provide indications of likely therapeutic effects, but cannot demonstrate clinical efficiency. Although anti-secretory drugs and prostaglandins can protect patients against the development of duodenal or gastric ulcers, but not both, there is no clinical evidence which bears upon the critical issue of protection against complications.
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Trefoil peptides are gut peptides that have been implicated in the repair of the gastric mucosa after injury. Previous studies suggest that epidermal growth factor (EGF) receptor ligands may induce the expression of trefoil peptides.... more
Trefoil peptides are gut peptides that have been implicated in the repair of the gastric mucosa after injury. Previous studies suggest that epidermal growth factor (EGF) receptor ligands may induce the expression of trefoil peptides. Because transforming growth factor-alpha (TGF-alpha) is a major EGF receptor ligand in the gut, we tested the hypothesis that mice with a TGF-alpha null mutation (knockout) would have reduced trefoil peptide expression compared with wild-type controls after gastric ulceration. The rate of macroscopic ulcer healing was the same in knockout and wild-type mice. Spasmolytic polypeptide (SP) and intestinal trefoil factor (ITF) expression were quantified in tissue and gastric lavage. SP and ITF levels in tissue fell within 48 h of ulceration (P < 0.05), but secretion into gastric juice was unchanged. ITF peptide expression was increased (as was SP expression) in wild-type but not knockout mice 42 and 72 days after injury (P < 0.05). The induction of SP and ITF expression in the latter stages of injury repair has a TGF-alpha-dependent component and suggests a role for these peptides in gastric differentiation and cell positioning.
Research Interests: Neuropeptides, Intestinal Mucosa, Mice, Animals, Peptides, and 3 moreTime Factors, Mucins, and Duodenum
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The subsequent recurrence rate after duodenal ulcers were healed with omeprazole, 10 mg or 30 mg a day, was documented during a 12-month period in 55 patients. Endoscopy was performed if patients developed symptomatic recurrence; those... more
The subsequent recurrence rate after duodenal ulcers were healed with omeprazole, 10 mg or 30 mg a day, was documented during a 12-month period in 55 patients. Endoscopy was performed if patients developed symptomatic recurrence; those patients who remained symptom-free at 12 months were also requested to undergo endoscopy to assess the incidence of asymptomatic recurrence. The proportion with symptomatic recurrence during the year was 56%. The median times (life-table analysis) to relapse were 50 and 39 weeks in the group that was treated initially with 30 mg and 10 mg of omeprazole, respectively, although this trend to slower relapse in the higher-dose group was not statistically significant. Five asymptomatic ulcers were detected in 11 asymptomatic subjects who agreed to a final endoscopy. The over-all recurrence rate was similar to previously-reported recurrence rates after the cessation of histamine H2-receptor antagonist drugs.