Prospective study of acute gastrointestinal bleeding attributable to anti-inflammatory drug ingestion in the Yorkshire region of the United Kingdom.

OBJECTIVE: To assess the general use of all non-steroidal anti-inflammatory drugs (NSAID) and their relation to upper gastrointestinal bleeding in view of National Institute for Clinical Excellence guidelines published in July 2001 in the UK. METHODS: Cross sectional study on all patients who were referred for endoscopy for suspected upper gastrointestinal bleeding in six hospitals in Yorkshire region of the UK. RESULTS: One hundred and sixty three patients presented for endoscopy for suspected upper gastrointestinal bleeding, 43 patients were taking at least one ulcerogenic drug, and 120 were not. The mean age difference between these two groups was eight years (p<0.01). The absolute difference between the proportion of patients with peptic ulcer disease/erosion (PUD) in NSAID with/without aspirin group and no ulcerogenic drug group was 31% (p = 0.02). The difference between the proportion of PUD in cyclo-oxygenase 2 with/without aspirin group and no ulcerogenic drug group was 30% (p = 0.1). The overall 30 days mortality rate was 14.1%. CONCLUSIONS: Elderly patients are being inappropriately prescribed conventional NSAIDs. NSAIDs with or without aspirin use are still associated with a significant risk of upper gastrointestinal bleeding in the era of cyclo-oxygenase 2 selective agents. Substitution with cyclo-oxygenase 2 selective NSAIDs is not without risk of upper gastrointestinal bleeding.

Review article: psychosocial factors in the quality of life of patients with inflammatory bowel disease.

Information on quality of life in inflammatory bowel disease is limited. Despite the clear importance of this topic to patients, quality of life measurement is seldom undertaken in day-to-day management of patients or included in clinical trials. Although previous reviews have dealt with quality of life, the area of psychosocial functioning has not been specifically addressed. The aim of this study was to review the psychosocial factors affecting quality of life in patients with inflammatory bowel disease, using an electronic search of MEDLINE, EMBASE, CINAHL and psycINFO. Of the 751 articles identified by the search, 107 were considered relevant and included in the review. A number of psychosocial factors appear to be important, including gender, socioeconomic status, ethnicity and perceived stress. To improve the quality of life in patients with inflammatory bowel disease, clinicians' attention needs to be drawn towards this subject, with an awareness of those patient groups more vulnerable to impaired quality of life. These identified variables also represent important factors, which should be adjusted for when conducting research into quality of life in these patients.

Variation in serum pepsinogens with severity and topography of Helicobacter pylori-associated chronic gastritis in dyspeptic patients referred for endoscopy.

BACKGROUND: It has long been recognised that specific patterns of gastritis are linked with different gastroduodenal diseases and that serum pepsinogens vary with the histological state of the gastric mucosa. With the discovery of the role of Helicobacter pylori in chronic gastritis and the availability of noninvasive tests for H. pylori infection, individuals with H. pylori gastritis can now be identified without endoscopic biopsy. However, without a knowledge of the pattern and severity of gastritis it is impossible to predict the likelihood of significant associated gastroduodenal pathology. AIMS: The aim of this study was to evaluate the diagnostic potential of serum pepsinogens I and II in predicting the topography and severity of gastritis in H. pylori-infected dyspeptic patients attending for endoscopy. METHODS: Fasting serum was obtained from consecutive dyspeptic patients attending for endoscopy, and pairs of gastric biopsies obtained from the mid-body and antrum. Gastritis was graded according to the Sydney System, and serum pepsinogen levels determined by radio-immunoassay. RESULTS: Sixty-nine dyspeptic patients were studied (mean age: 49.6 years) of whom 34 had H. pylori-associated chronic gastritis (Hp-gastritis) - antral predominant gastritis (APG) in 41.2%, pangastritis (PAN) in 52.9%, and corpus predominant (CPG) in 5.9%. Serum pepsinogen II levels were significantly higher, and the serum pepsinogen I : II ratio significantly lower, in the H. pylori positive group than in other groups. Within the Hp-gastritis group, there was a step-wise decrease in serum pepsinogen I levels with progression from APG through PAN to CPG pattern (a cut-off value of > or = 100 ng/ml would have identified APG with a positive predictive value of 77%, though with low sensitivity). Within the Hp-gastritis group, serum pepsinogen I and II levels were correlated with antral chronic inflammation score and serum pepsinogen II levels also with antral activity score. Serum pepsinogen I and the pepsinogen I : II ratio were lowest in severe gastric corpus atrophy. CONCLUSION: In dyspeptic patients known to be infected with H. pylori, serum pepsinogen values provide an assessment of the overall topography of gastritis, the severity of antral inflammation and the presence of severe corpus atrophy.

Interleukin 10 in Helicobacter pylori associated gastritis: immunohistochemical localisation and in vitro effects on cytokine secretion.

BACKGROUND/AIMS: Interleukin 10 (IL-10) is a counter-inflammatory peptide implicated in the downregulation of human intestinal immune responses. Enhanced secretion of IL-10 has been documented in gastric biopsy organ culture in Helicobacter pylori infection. This study aimed to define the cellular origins of IL-10 in H pylori associated gastritis, and to determine the effects of endogenous IL-10 on proinflammatory cytokine secretion in vitro. METHODS: Endoscopic biopsies were obtained from the gastric antrum at endoscopy from patients with dyspepsia. Two pairs of antral biopsies were cultured in vitro for 24 hours, one pair in the presence of neutralising anti-IL-10 monoclonal antibody, the other pair as controls. The cytokine content of culture supernatants (tumour necrosis factor alpha (TNF-alpha), IL-6, and IL-8) was determined by enzyme linked immunosorbent assay and corrected for biopsy weight. Helicobacter pylori status was established by histology and biopsy urease test, and histopathology graded by the Sydney system. In a subgroup of patients, western blotting was used to establish CagA serological status. Immunohistochemistry for IL-10 was performed on formalin fixed tissues using a combination of microwave antigen retrieval and the indirect avidin-biotin technique. Immunoreactivity was scored semiquantitatively. RESULTS: In vitro culture was performed in 41 patients: 31 with H pylori positive chronic gastritis and 10 H pylori negative. In vitro secretion of TNF-alpha, IL-6, and IL-8 for "control" biopsies was significantly higher in H pylori positive versus negative samples, with values of TNF-alpha and IL-6 correlating with the degree of active and chronic inflammation and being higher in CagA seropositive cases. No evidence for enhanced cytokine secretion was seen in biopsies cocultured in the presence of anti-IL-10 monoclonal antibody. Immunohistochemistry was performed in 29 patients, of whom 13 were H pylori positive. IL-10 immunoreactivity was observed in the surface epithelium in all H pylori positive cases and in 13 of 16 negative cases, especially in areas of surface epithelial degeneration. Lamina propria mononuclear cells (LPMNCs) were positively stained in all H pylori positive cases and in 12 of 16 negative cases, with a significantly greater proportion of positive LPMNCs in the positive group. CONCLUSIONS: This study localised IL-10 protein to the gastric epithelium and LPMNCs. In vitro proinflammatory cytokine secretion was increased in H pylori infection (especially CagA positive infection), but blocking endogenous IL-10 secretion did not significantly increase cytokine secretion. IL-10 is implicated in H pylori infection and might "damp down" local inflammation. The role of gastric IL-10 secretion in determining the clinicopathological outcome of infection merits further study.

Medical treatment of gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease is common and is a chronic recurring condition. In view of our improved knowledge about the pathogenesis and complications of gastro-oesophageal reflux, the therapy should be individualized and a cost-effective approach should be attempted in its management.

Dyspepsia workload in urban general practice and implications of the British Society of Gastroenterology Dyspepsia guidelines (1996).

AIM: To define the characteristics of patients consulting with active dyspeptic symptoms in urban general practice, and to consider the implications of applying the British Society of Gastroenterology Dyspepsia management guidelines. DESIGN: Prospective observational study over a period of 12 months. SETTING: Two multipartner, two-centre general practices in the City of Leeds (UK) with a combined target population of 11 011 registered patients. SUBJECTS: A total of 340 patients consulting with active dyspeptic symptoms (52% male; mean age 53 years, range 16-89 years). RESULTS: Of the practice population, 3% consulted with dyspepsia (first-time consulter: 19%; previous consulter not yet investigated: 30%; previously investigated: 51%). Of 168 undiagnosed patients, 43% had upper abdominal pain (dysmotility-like symptoms in 42%), 35% had reflux symptoms, 22% had mixed symptoms, 12% had 'alarm' symptoms and 18% had a history of NSAID use. Patients < 45 years old with simple dyspepsia accounted for 32% of undiagnosed cases. A fifth of the workload was in dealing with undiagnosed dyspeptics over 45 years old. One per cent of the population would require endoscopy if all undiagnosed cases either > 45 years or with complicated dyspepsia were investigated. Of 172 previously investigated patients, 29% had negative tests, 25% had 'minor' findings, and 45% had evidence of acid-peptic disease. Patients with duodenal ulcer disease accounted for 12% of the total workload. CONCLUSIONS: A knowledge of the characteristics of patients consulting with dyspepsia in primary care should allow the adaptation of guidelines, to ensure advice is relevant to local case mix and compatible with local resources.

Safety of proton-pump inhibitors: the acid test.

It is well established that atrophic gastritis, pernicious anaemia and partial gastrectomy are associated with an increased risk of gastric carcinoma. These conditions all result in a low acid output state. Although the mechanism of gastric carcinogenesis is not known, the model proposed by Correa has provided the most attractive explanation to date. The suggestion is that prolonged hypochlorhydria predisposes to gastric carcinoma by an increase in the production of carcinogenic N-nitroso compounds. This hypothesis has led to concerns about the safety of long-term acid suppression in the management of a variety of acid-related gastrointestinal conditions.

Serologic screening before endoscopy: the value of Helicobacter pylori serology, serum recognition of the CagA and VacA proteins, and serum pepsinogen I.

BACKGROUND: We wanted to assess the diagnostic value of pre-endoscopy screening by Helicobacter pylori serology, serum recognition of the CagA and VacA proteins, and serum pepsinogen I levels (sPGI) in patients up to 55 years of age with uncomplicated simple dyspepsia. METHODS: Consecutive dyspeptic patients referred for open-access endoscopy, excluding patients with alarm symptoms, recent intake of acid suppressants, or ingestion of non-steroidal anti-inflammatory drugs. H. pylori status was determined by histology and urease testing. H. pylori serologic status was determined with the enzyme-linked immunosorbent assay (ELISA) and Western blotting, serum recognition of CagA and VacA with Western blot, and sPGI levels by radioimmunoassay. RESULTS: One hundred and fifteen patients were studied (mean age, 40 years: range, 20-55 years), of whom 58 were H. pylori-positive in biopsy-based tests. Twenty-one patients (18%) had significant gastroduodenal lesions (erosions, ulcers, or cancer). The sensitivity (specificity) of the ELISA (optimized) and Western blot in determining H. pylori status was 94.8% (89.5%) and 100% (96.4%), respectively. Screening strategies based on the ELISA or Western blot for determining H. pylori serologic status would have detected 95% or 100% of significant lesions, respectively, and each 'saved' 47% of endoscopies for simple dyspepsia. Serum recognition of the CagA protein would have detected 95% of significant lesions and 'saved' 55% of endoscopies, whereas recognition of the VacA protein would have detected only 81% of the lesions. Screening by H. pylori serology plus a 'low' (<55 ng/ml) or 'high' sPGI (>125 ng/ml) would detect only 57% of significant lesions, although the only case of cancer was included in the hypopepsinogenaemic subgroup of just 11 patients. CONCLUSIONS: In patients with uncomplicated, simple dyspepsia up to 55 years of age, screening by H. pylori serology identified 95%-100% of patients with significant gastroduodenal lesions while potentially saving 46.9% of endoscopies. Serum recognition of the CagA protein identified 95% of lesions and would have saved an additional number of endoscopies (7.9%) compared with basic serology. Measurement of sPGI was of limited diagnostic value.

Clinical economics review: medical management of inflammatory bowel disease.

Inflammatory bowel diseases, although they are uncommon and rarely fatal, typically present during the period of economically productive adult life. Patients may require extensive therapeutic intervention as a result of the chronic, relapsing nature of the diseases. Their medical management includes oral and topical 5-amino salicylic acid derivatives and corticosteroids, as well as antibiotics and immunosuppressive therapies. Assessing the cost-effectiveness of rival treatments requires valid, reliable global assessments of outcome which consider quality of life, as well as the usual clinical end-points. Macro-economic studies of the overall impact of inflammatory bowel disease on health care systems have so far been largely confined to North America, where the total annual US costs, both direct and indirect, incurred by the estimated 380 000-480 000 sufferers has been put at around US2bn. Drugs were estimated to account for only 10% of total costs, whereas surgery and hospitalization account for approximately half. Studies from Europe suggest that the proportion of patients with Crohn's disease and ulcerative colitis who are capable of full time work is 75% and 90%, respectively. However, whilst only a minority of inflammatory bowel disease patients suffer chronic ill health and their life expectancy is normal, obtaining life assurance may be problematic, suggesting a misconception that inflammatory bowel disease frequently results in a major impact on an individual's economic productivity.

Barrett's oesophagus--a ray of hope.

The incidence of oesophageal cancer at the cardia is believed to be increasing, especially in younger individuals. Although the causes are unknown, Barrett's oesophagus may be such a cause, since it has a proven pre-malignant potential. It is generally believed that long-standing gastro-oesophageal reflux disease predisposes to columnar transformation in the oesophagus, although it is unclear whether medical or surgical treatment has significant effects in the long term.

Gastric mucosal secretion of interleukin-10: relations to histopathology, Helicobacter pylori status, and tumour necrosis factor-alpha secretion.

BACKGROUND: Interleukin-10 (IL-10) is an 18 kDa peptide with a range of anti-inflammatory and immunosuppressive properties. AIM: To determine whether this cytokine is involved in gastric mucosal inflammation in Helicobacter pylori infection. METHODS: The production of IL-10 by antral mucosal biopsy specimens during short term in vitro culture was determined by measuring IL-10 content of supernatants by enzyme linked immunosorbent assay (ELISA). H pylori status was determined by serology and histology, with gastritis scored using the Sydney system. Tumour necrosis factor-alpha (TNF-alpha) content of supernatants was also determined in a subgroup of patients. RESULTS: IL-10 secretion was significantly greater in patients with H pylori associated chronic gastritis than in patients who were H pylori negative with normal mucosa/reactive changes, and those with H pylori negative chronic gastritis (p < 0.01 and < 0.05 respectively). There was a significant correlation overall between IL-10 secretion and chronic inflammation score (r = 0.40). Secretion of TNF-alpha, which was significantly higher in H pylori infected patients than uninfected patients with a normal mucosa (p < 0.04), correlated with scores for chronic inflammation and activity (r = 0.39 and 0.38 respectively), but was only weakly correlated with IL-10 secretion (r = 0.22, NS). CONCLUSIONS: Gastric mucosal production of IL-10 and TNF-alpha are increased in chronic gastritis associated with H pylori infection, and mucosal cytokine secretion varies with important histopathological aspects of gastric inflammation. Whereas the secretion of IL-10 in H pylori infection may be protective, limiting tissue damage caused by inflammation, it may also contribute towards failure of the immune response to eliminate the organism.

Clinical economics review: Helicobacter pylori-associated peptic ulcer disease.

The high prevalence and chronic nature of peptic ulcer disease have traditionally resulted in a major economic burden on health care systems. In 1991, for example, peptic ulcer disease was estimated to account for over one-third of all National Health Service expenditure on gastrointestinal diseases. It is now well established that elimination of Helicobacter pylori can lead to a dramatic reduction in gastroduodenal ulcer relapse, with obvious clinical benefits. This review considers the economic implications of the use of H. pylori eradication therapy in peptic ulcer disease.