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Biomedical subjects

C A O'Morain

Publications and source records attributed to C A O'Morain.

At least 19 recordsLinked to original sources

Impact of Helicobacter pylori on the management of dyspepsia in primary care.

BACKGROUND: It is unclear what impact Helicobacter pylori infection has had on the management of dyspepsia in primary care and to what extent published guidelines on H. pylori are implemented in routine clinical practice. AIM: To assess the impact of H. pylori infection on the management of dyspepsia in primary care. METHODS: Patients referred by primary care doctors to an open-access 13-carbon urea breath test service over a 2-year period for their first urea breath test were included in the study. Individual breath results were linked with data on prescribing obtained from the General Medical Services prescription database. RESULTS: Of 805 patients, 374 (47%) had a positive urea breath test and 431 (54%) a negative urea breath test. Of positive urea breath test patients, only 245 (64%) were prescribed eradication therapy in the 3 months after the breath test and only 43% were referred back for re-testing. In the year after the urea breath test, there was a significant fall in prescribing of antisecretory therapy which was greatest in the patients who received H. pylori therapy (P < 0.001). CONCLUSIONS: There appears to be under and inappropriate treatment of H. pylori infection in primary care, and a low rate of re-testing after eradication, indicating that current guidelines are not well implemented in practice.

Adult↗

Endoscopic argon plasma coagulation for the treatment of gastric antral vascular ectasia (watermelon stomach): long-term results.

INTRODUCTION: Gastric antral vascular ectasia is a rare but well-recognised cause of occult gastrointestinal bleeding. Various endoscopic treatments have been tried in this condition. We report our experience with argon plasma coagulation in the treatment of gastric antral vascular ectasia. PATIENTS AND METHODS: Twelve patients with endoscopically proved gastric antral vascular ectasia were included. All patients received argon plasma coagulation with power of 40 W at a median interval of 4 weeks. The pre-treatment haemoglobin and transfusion requirements were compared with the post-treatment values. RESULTS: There was a sustained increase in mean haemoglobin levels post-treatment. The mean haemoglobin levels pre- and post-treatment were 8.13 +/- 0.70 and 12.2 +/- 0.32 g/dl, respectively (P = 0.008). All patients were anaemic and 58.3% of the patients were transfusion dependent. The mean number of units of blood transfusion in the period 6 months prior to treatment was 11.3 +/- 5.68. Following argon plasma coagulation, the number of transfusions decreased significantly to 1.1 +/- 0.57 units (P = 0.018). No significant procedure-related complications were identified. CONCLUSION: Argon plasma coagulation is a safe and effective alternative to the currently available endoscopic modalities of treatment for gastric antral vascular ectasia.

Aged↗

Review article: current therapeutic options for gastric antral vascular ectasia.

Gastric antral vascular ectasia, or 'watermelon stomach', is a rare but important cause of gastrointestinal blood loss and anaemia, which has characteristic endoscopic and histological features. The pathogenesis of this condition remains unclear; however, many associated disorders have been documented. Various medical, surgical and endoscopic therapeutic modalities have been attempted with variable success. Leading contenders for the therapeutic modality of choice include hormonal therapy, endoscopic Nd:YAG laser and argon plasma coagulation. Randomized controlled trials to identify the ideal treatment method are lacking at present.

Adrenal Cortex Hormones↗

Clinical and pathological implications of IgG antibody responses to Helicobacter pylori and its virulence factors in non-ulcer dyspepsia.

AIM: To determine whether pre-treatment antibody response to Helicobacter pylori virulence factors predicts eradication success and symptom relief 12 months after triple therapy in non-ulcer dyspepsia. METHODS: H. pylori-positive patients with non-ulcer dyspepsia received 1-week omeprazole-based triple therapy, or omeprazole plus placebos. Symptoms were assessed using a validated Likert scale. Gastric biopsies taken before and 12 months after treatment were used for histological examination. Pre-treatment blood samples were used for the detection of anti-H. pylori immunoglobulin G (IgG) antibodies, and specific IgG antibodies to 19.5-, 26.5-, 30-, 35-, 89- (VacA) and 116-kDa (CagA) antigens of H. pylori. RESULTS: IgG antibodies to the six antigens were detected in 62%, 96%, 88%, 47%, 54% and 78% of patients, respectively. The presence of antibody to 19.5-, 26.5- or 30-kDa antigen was associated with an increased anti-H. pylori IgG absorbance index. IgG absorbance indices were greater in those with H. pylori eradication (vs. persistent infection). The prevalence of antibodies to the six antigens was not significantly different between those with symptom relief vs. those without. The 19.5-kDa antigen (P = 0.018) and VacA (P = 0.001) were independent risk factors for body gastritis. CONCLUSIONS: An increased pre-treatment anti-H. pylori IgG absorbance index may be a useful predictor of the success of eradication therapy. Although the 19.5-kDa antigen and VacA were associated with body gastritis, none of the six antigens tested predicted symptom relief after triple therapy.

Adult↗

Review article: test and treat or test and scope for Helicobacter pylori infection. Any change in gastric cancer prevention?

A 'test and treat' strategy is advocated for patients with dyspepsia under the age of 45 years, with endoscopy reserved for those with alarm symptoms or aged over 45 years. One of the consequences of this strategy will be a reduction in population infection rates of Helicobacter pylori. It is now clear that H. pylori is one of the prime initiators of gastric cancer with up to 70% of gastric cancers attributable to H. pylori. What remains unclear is if H. pylori reduction will lead to a reduction in gastric cancer.

Helicobacter Infections↗

Review article: nutrition and adult inflammatory bowel disease.

Major advances in the understanding of the aetio-pathogenesis and genetics of inflammatory bowel disease have been accompanied by an escalation in the sophistication of immunomodulatory inflammatory bowel disease therapeutics. However, the basic 'triple' therapy (5-aminosalicylates, corticosteroids, azathioprine) and nutrition have maintained their central role in the management of patients with inflammatory bowel disease over recent decades. This review provides an overview of the supportive and therapeutic perspectives of nutrition in adult inflammatory bowel disease. The objective of supportive nutrition is to correct malnutrition in terms of calorie intake or specific macro- or micronutrients. Of particular clinical relevance is deficiency in calcium, vitamin D, folate, vitamin B12 and zinc. There is justifiably a growing sense of unease amongst clinicians and patients with regard to the long-term use of corticosteroids in inflammatory bowel disease. This, rather than arguments about efficacy, should be the catalyst for revisiting the use of enteral nutrition as primary treatment in Crohn's disease. Treatment failure is usually related to a failure to comply with enteral nutrition. Potential factors that militate against successful completion of enteral nutrition are feed palatability, inability to stay on a solid-free diet for weeks, social inconvenience and transient feed-related adverse reactions. Actions that can be taken to improve treatment outcome include the provision of good support from dietitians and clinicians for the duration of treatment and the subsequent 'weaning' period. There is evidence to support a gradual return to a normal diet through exclusion-re-introduction or other dietary regimen following the completion of enteral nutrition to increase remission rates. We also review the evidence for emerging therapies, such as glutamine, growth factors and short-chain fatty acids. The future may see the evolution of enteral nutrition into an important therapeutic strategy, and the design of a 'Crohn's disease-specific formulation' that is individually tailored, acceptable to patients, cost-effective, free from adverse side-effects and combines enteral nutrition with novel pre- and pro-biotics and other factors.

Butyrates↗

Review article: treatment of Helicobacter pylori infection and factors influencing eradication.

Currently available Helicobacter pylori eradication therapies are considered very effective and safe. The most recent eradication guidelines proposed in the Maastricht 2-2000 Consensus Report recommend the use of proton pump inhibitors (standard b.d.) along with clarithromycin (500 mg b.d.) and amoxycillin (1000 mg b.d.) or metronidazole (500 mg b.d.) for a minimum of 7 days. The combination of amoxycillin and clarithromycin is preferred because it may favour best results with a second-line proton pump inhibitor quadruple therapy. The recommended second-line therapy includes a combination of a proton pump inhibitor (standard b.d.) with bismuth salt (subsalicylate/subcitrate 120 mg q.d.s.), metronidazole (500 mg t.d.s.), and tetracycline (500 mg q.d.s.) for a minimum of 7 days. Extended proton pump inhibitor-based triple therapy can be used if bismuth is not available. Specialists should manage subsequent failures. Based on direct and indirect evidence from well-designed studies and clinical experience, eradication is recommended in gastric and duodenal ulcers, MALToma, atrophic gastritis, postgastric cancer resection, and in first-degree relatives of gastric cancer patients. The most common reason for treatment failure is poor compliance with eradication guidelines. Antibiotic resistance may be a significant factor in certain geographical areas. Proton pump inhibitors are an integral part of the eradication regimens as proved by meta-analyses of clinical trials. Novel agents used in secondary failure are few and depend on the use of new antibiotics. The role of H. pylori-specific antibiotics, probiotics, and vaccines is not established as yet. Widespread acceptance of the eradication guidelines should be regarded as the single most important factor in eradication success.

Drug Resistance, Bacterial↗

Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease.

Crohn's disease and ulcerative colitis, the two main types of chronic inflammatory bowel disease, are multifactorial conditions of unknown aetiology. A susceptibility locus for Crohn's disease has been mapped to chromosome 16. Here we have used a positional-cloning strategy, based on linkage analysis followed by linkage disequilibrium mapping, to identify three independent associations for Crohn's disease: a frameshift variant and two missense variants of NOD2, encoding a member of the Apaf-1/Ced-4 superfamily of apoptosis regulators that is expressed in monocytes. These NOD2 variants alter the structure of either the leucine-rich repeat domain of the protein or the adjacent region. NOD2 activates nuclear factor NF-kB; this activating function is regulated by the carboxy-terminal leucine-rich repeat domain, which has an inhibitory role and also acts as an intracellular receptor for components of microbial pathogens. These observations suggest that the NOD2 gene product confers susceptibility to Crohn's disease by altering the recognition of these components and/or by over-activating NF-kB in monocytes, thus documenting a molecular model for the pathogenic mechanism of Crohn's disease that can now be further investigated.

Alleles↗

Identification of genes regulated by prolonged acid exposure in Helicobacter pylori.

To investigate the influence of prolonged acid exposure on the gene expression, transcripts of Helicobacter pylori, grown under pH 5.5 and pH 7.4 for five successive passages, were analysed by differential display PCR. Eight genes were regulated by prolonged acid exposure. These genes included topA, tufB, ureB, flaA, atoE in the H. pylori genome and a cDNA fragment with 54% identity of the predicted amino acid sequence to a Bacillus cereus YkoW protein. The remaining two cDNA fragments had no significant homology to known sequences. Our data suggest that most of these genes might be required for the resistance of H. pylori to prolonged acid exposure.

Acids↗

A double-blind placebo-controlled study of buspirone-stimulated prolactin release in non-ulcer dyspepsia--are central serotoninergic responses enhanced?

BACKGROUND: Dyspepsia is a common symptom for which an organic cause is found in only 40% of patients. When no cause is apparent and the dyspepsia is considered to be idiopathic, a diagnosis of non-ulcer dyspepsia is made. The pathophysiology of non-ulcer dyspepsia is poorly understood and numerous theories have been put forward, including a theory of enhanced central serotoninergic receptor sensitivity. AIM: To determine the sensitivity of serotonin receptors in non-ulcer dyspepsia. METHODS: Using a randomized, double-blind, placebo-controlled design, we compared buspirone (a serotonin type 1a partial agonist)-stimulated prolactin release in 50 patients and 59 healthy comparison subjects. Buspirone, 30 mg, or matching placebo was administered on two separate occasions and prolactin release over 180 min was monitored. Patients and healthy subjects received both treatments in random order, 1 week apart. RESULTS: Overall, patients with non-ulcer dyspepsia had greater prolactin release in response to the buspirone challenge than the healthy comparison subjects, with differences most significant at 90 min following the challenge. Enhancement occurred in patients both with and without Helicobacter pylori infection. Female subjects, both patients and healthy volunteers, showed a greater response to buspirone than male subjects, and the augmentation of response observed in male and female patients was greater in females. CONCLUSIONS: Patients with non-ulcer dyspepsia have enhanced central serotoninergic responses and such responses are independent of H. pylori infection. Blockade of such receptors might be an appropriate therapeutic strategy.

Adult↗

Olsalazine is not superior to placebo in maintaining remission of inactive Crohn's colitis and ileocolitis: a double blind, parallel, randomised, multicentre study.

BACKGROUND AND AIMS: The benefit of 5-aminosalicylic acid therapy for maintenance of remission in Crohn's disease is controversial. The primary aim of this study was to evaluate the prophylactic properties of olsalazine in comparison with placebo for maintenance of remission in quiescent Crohn's colitis and/or ileocolitis. METHODS: In this randomised, double blind, parallel group study of olsalazine versus placebo, 328 patients with quiescent Crohn's colitis and/or ileocolitis were recruited. Treatment consisted of olsalazine 2.0 g daily or placebo for 52 weeks. The primary end point of efficacy was relapse, as defined by the Crohn's disease activity index (CDAI) and by clinical relapse. Laboratory and clinical disease activity indicators were also measured. Safety analysis consisted of documentation of adverse events and laboratory values. RESULTS: No differences in the frequency of termination due to relapse or time to termination due to relapse were noted between the two treatment groups (olsalazine 48.5% v placebo 45%) for either colitis or ileocolitis. The failure rate, defined as not completing the study, was significantly higher in olsalazine treated patients compared with placebo treated patients for the overall population (colitis and/or ileocolitis: olsalazine 65.4% v 53.9%; p=0.038). Similar failure rates were seen for patients with colitis. A significantly higher percentage of olsalazine treated patients experienced adverse gastrointestinal events. Drug attributed adverse events were reported more frequently in the olsalazine treated group with gastrointestinal symptoms being causally related to olsalazine treatment (olsalazine 40.7% v placebo 26.9%; p=0.010). Back pain was reported significantly more often by the placebo treated group. However, serious medical events did not differ between the two groups. Adverse events led to more early withdrawals in the olsalazine treated group than in the placebo treated group; thus average time in the study for patients in the olsalazine treatment group was significantly shorter than that of patients in the placebo group. CONCLUSIONS: Patients treated with olsalazine were more likely to terminate their participation in the trial than those taking placebo. This difference was not related to relapse of disease, as measured by CDAI and clinical measures, but rather was due to the development of intolerable adverse medical events of a non-serious nature related to the gastrointestinal tract. The gastrointestinal related events in the olsalazine treated group may be due to the difference in gastrointestinal status at baseline which favoured the placebo treatment group.

Adolescent↗

Nonulcer dyspepsia. Current concepts and management.

NUD is a common heterogeneous condition with a multifactorial cause. NUD is a cause of considerable morbidity with an annual incidence of 8% and similar incidence of spontaneous resolution. Its economic effects are considerable. The estimated annual cost to the community of NUD is $431 per patient for the initial 6 months after diagnosis. The annual Health Maintenance Organization (HMO) expenditure on acid-related disorders in one Northern California HMO was estimated to be $59.4 million, of which NUD represented a significant proportion. The association of H. pylori infection with NUD is controversial. There are strong epidemiologic evidence and supportive pathophysiological mechanisms to implicate H. pylori causally in a subset of cases. Treatment studies are likewise conflicting. Evidence suggests that treatment cannot guarantee improvement in all cases of H. pylori-related NUD but that a subset would benefit with complete symptom resolution in the long term. It is not possible currently to predict which patients would or would not respond to eradication therapy. The strength of evidence is such that empiric eradication therapy, based on noninvasive H. pylori testing, can be advocated in young patients with dyspepsia safely and effectively with resultant financial savings.

Algorithms↗

Bacterial supplementation in the irritable bowel syndrome. A randomised double-blind placebo-controlled crossover study.

BACKGROUND: Symptoms of at least a subgroup of patients with irritable bowel syndrome may be associated with an alteration in gut flora. Studies on bacterial based therapy have yielded mixed results. AIMS: To determine if oral administration of the probiotic Lactobacillus casei strain GG under randomized placebo controlled conditions improves symptoms in irritable bowel syndrome patients with bloating related symptoms. PATIENTS: A total of 25 patients with clinically confirmed irritable bowel syndrome (Rome criteria) were enrolled in the study. METHODS: This was a randomised double-blind placebo-controlled crossover trial. Lactobacillus GG was administered as enterocoated tablets constituting a daily dosage of 10(10) colony forming units. Symptoms were assessed by daily symptom diaries and periodic questionnaires. RESULTS: Twenty-four patients were randomised; 19 (80%) female, mean age 40 years (range 24-60), mean duration of symptoms 4.9 years (range 0.5-18). Nineteen (80%) patients completed the study. No significant differences were found between Lactobacillus casei strain GG and placebo mean symptom scores for pain, urgency or bloating. A trend was noted, however, for a reduction in the number of unformed bowel motions on Lactobacillus casei strain GG treatment for patients with diarrhoea. CONCLUSIONS: Lactobacillus casei strain GG alone did not significantly improve symptoms in this irritable bowel syndrome subgroup. A "diarrhoea predominant" subgroup may warrant further investigation.

Adult↗

Increased mast cells in the irritable bowel syndrome.

Mast cells (MC) release potent mediators which alter enteric nerve and smooth muscle function and may play a role in the pathogenesis of the irritable bowel syndrome (IBS). The aim of this study was to determine if MC were increased in the colon of IBS patients compared to controls. Biopsy specimens were obtained from the caecum, ascending colon, descending colon and rectum of 28 patients: 14 IBS (Rome criteria); seven normal; and seven inflammatory controls. Tissue was stained immunohistochemically using a monoclonal mouse antibody for human mast cell tryptase (AA1). Tissue area occupied by tryptase-positive MC (volume density of mast cells) was quantified by image analysis. The number of plasma cells, lymphocytes, eosinophils, neutrophils and macrophages were each graded semiquantitatively (0-4) in haematoxylin and eosin stained sections. Mast cell volume density was significantly (P < 0.05) higher in IBS (0.91 +/- 0.18; CI 0.79; 1.0) than normal controls (0.55 +/- 0.14; CI 0.40; 0.69) in the caecum but not at other sites. Apart from MC, there was no evidence of increased cellular infiltrate in the IBS group. MC were significantly increased in the caecum of IBS patients compared to controls. The multiple effects of the intestinal mast cell alone, or as a participant of a persistent inflammatory response, may be fundamental to the pathogenesis of IBS.

Adult↗

Patient knowledge and educational needs in irritable bowel syndrome.

OBJECTIVE: Educating patients with irritable bowel syndrome (IBS) about their disorder may promote a strong physician-patient interaction, is a recommended approach for treating mild IBS and may reduce healthcare use. Our aim was to identify the information needs, levels and associated factors in IBS, and to contrast this with patients with inflammatory bowel disease (IBD). DESIGN: Seventy adult IBS patients (Rome criteria) were prospectively recruited, together with 82 ulcerative colitis (UC) and 60 Crohn's disease (CD) patients. Demographic data, clinical data, and anxiety and depression scores (HAD scale) were recorded. Patients rated their perceived levels of disease knowledge and satisfaction with their knowledge level on visual analogue scales. Qualitative data on disease information needs were obtained by an open-ended question. SETTING: Gastroenterology out-patient clinic. RESULTS: The majority of IBS patients (77%; n = 54) and over half of IBD patients (56%; n = 79) required further information about their disease. The primary issues for IBS patients were bowel cancer risk and diet. Queries about medications ranked top for UC, while prognosis and cancer risk jointly ranked top for CD. In the IBS group, 27% rated their knowledge as < 25 out of 100 compared to 10% of IBD patients. The perceived level of knowledge in IBS was significantly negatively associated with length of hospital consulting (r(s) = -0.32; P = 0.04). CONCLUSION: Most IBS patients feel insufficiently informed, particularly in relation to risk of serious disease and role of diet. Educating IBS patients about their disorder may play a role in reducing healthcare use.

Adult↗