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AIMS: To investigate whether Helicobacter pylori infection or autoimmune gastritis is responsible for the reported increase in gastric pathology and abnormalities of gastric function in patients with coeliac disease and dermatitis herpetiformis (DH). METHODS: Serum H pylori IgG antibodies were assayed by enzyme linked immunosorbent assay and intrinsic factor antibodies by radioimmunoassay in 99 patients with coeliac disease and 58 patients with dermatitis herpetiformis from two geographic areas. RESULTS: H pylori positivity in patients with coeliac disease and dermatitis herpetiformis increased with age, reaching 50% and 70%, respectively, in patients over 50 years. The percentage H pylori seropositivity in coeliac disease did not differ from the percentage positivity observed in 250 similarly aged blood donors from the same geographic area (Leeds). Seropositivity in patients with dermatitis herpetiformis was not significantly different from the level of positivity observed in 98 age matched patients without dermatitis herpetiformis attending the same Edinburgh dermatology clinic. Only one patient with coeliac disease had positive intrinsic factor antibodies. H pylori seropositivity in Edinburgh control subjects under 30 years of age (41.9%) was significantly higher (p less than 0.03) than in Leeds controls (18%) of corresponding age. An increasing prevalence of H pylori seropositivity with age in coeliac disease and dermatitis herpetiformis paralleled that of the control groups. CONCLUSIONS: Gastritis in coeliac disease and dermatitis herpetiformis is largely caused by H pylori infection at a level that is no different from that of the general population. Any increase in the prevalence of gastritis in these two diseases might be caused by lymphocytic gastritis rather than pernicious anaemia.

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.Prospective observational study over a period of 12 months.Two multipartner, two-centre general practices in the City of Leeds (UK) with a combined target population of 11 011 registered patients.A total of 340 patients consulting with active dyspeptic symptoms (52% male; mean age 53 years, range 16-89 years).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. Patients45 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 either45 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.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.

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.

The frequency of oesophageal ulceration in 55 patients undergoing endoscopy for dyspeptic symptoms and who had recently used NSAIDs was studied, and compared with 86 patients seen in the same clinic who had not recently used these drugs. Oesophageal ulceration was significantly more common in those who had used NSAIDs (P = 0.012), and also showed a highly significant association with the presence of a hiatus hernia (P less than 0.001). No association was found between the presence of gastric Helicobacter pylori and either oesophageal ulceration or histological oesophagitis. Patients receiving NSAIDs, especially those with a hiatus hernia, are at risk of oesophageal ulceration and presumably subsequent stricture formation. This should be borne in mind when prescribing these agents.

Dyspepsia can be the presenting feature of a range of underlying conditions. However, without investigation there is no way of being certain of its cause. Open-access upper gastrointestinal endoscopy, where a patient only comes to hospital for endoscopy, is becoming a popular investigation. There is much to commend this approach, but the careful selection of patients is important.

Spiral organisms have been recognized within the mammalian stomach for almost 100 years. There had, however, been interest in the association between bacteria and peptic ulcers even before that time. Although there have been occasional references over the years since this time, suggesting that a relationship may exist between various microorganisms and human peptic ulcer disease, until recent years few would have seriously credited any significant pathogenic role for bacteria in this condition1. In 1983 and early 1984, however, three separate groups almost simultaneously reported their observations relating to the association between a newly recognized spiral organism and chronic gastritis, and this has focused attention firmly on the role this agent may have in peptic ulcer disease1.

The prevalence of Helicobacter pylori was determined using an ELISA technique for IgG antibodies to H. pylori in 76 patients with end-stage renal failure who were receiving regular haemodialysis and 202 patients with functioning renal transplants. Twenty-seven (34%) of the haemodialysis group and 58 (29%) of the transplant group were positive for H. pylori IgG antibodies, and the prevalence did not differ significantly from that in 247 age-matched healthy controls. In the haemodialysis group, patients positive for H. pylori were older, median age 60 years (range 22-73), compared to those patients without H. pylori antibodies, median age 52 years (range 22-75), p less than 0.05, more suffered from dyspeptic symptoms, 35 vs. 10% (p less than 0.01), yet fewer had been prescribed aluminium-containing antacids, 38 vs. 78% (p less than 0.01). In the transplanted group, those positive for H. pylori were more symptomatic for dyspepsia, 30 vs. 11% (p less than 0.01), and had lower serum creatinine values, 136 +/- 10 mumol/l (mean +/- SEM) vs. 172 +/- 12 mumol/l (p less than 0.05), compared to those without H. pylori antibodies. Almost all the transplant patients with H. pylori antibodies were taking steroids (98%) compared to 84% of those without antibodies (p less than 0.05). The prevalence of antibodies to H. pylori in this study was increased in symptomatic dyspeptic subjects and reduced in those patients prescribed aluminium-containing phosphate binders.

Helicobacter pylori infection and chronic active gastritis are inextricably linked, and this organism is almost certainly responsible for inducing the resulting inflammatory changes. Acute ingestion studies have confirmed that H. pylori infection causes acute gastritis, and the progression to chronic gastritis has been documented. Duodenitis and H. pylori infection often occur concurrently, but colonization is restricted to those with significant gastric metaplasia. The association between H. pylori-induced inflammation and symptoms is at present unclear. In some treatment studies H. pylori eradication has been associated with a symptomatic response, whereas the acute inflammatory response appears frequently to subside H. pylori infection of the gastroduodenal mucosa is associated with both mucosal and systemic antibody responses. The mucosal response occurs both within the stomach and locally in the duodenum in patients with duodenitis. Mucosal cellular responses also appear active in patients with H. pylori gastritis. Cytokines are produced locally, which could have significant pathophysiologic effects. The concurrent use of non-steroidal anti-inflammatory agents in patients with H. pylori-induced gastritis may modify the subsequent inflammatory response. Although H. pylori is a major and consistent stimulus for inflammation within the gastroduodenal mucosa, our understanding of the development of these responses is far from complete. Inflammatory mediators are released during infection and probably play a major role in modulating the subsequent mucosal immune responses.

In vitro production of prostaglandin E2 and leukotriene B4 by colonic biopsies from patients with ulcerative colitis and controls were found to be dependent on current smoking habit in a dose dependent manner, being increased in light smokers but reduced in moderate and heavy smokers.

Production of prostaglandin E2, and to a lesser extent leukotriene B4, by the colonic mucosa in vitro was shown to be increased in recent ex-smokers (

Demand for endoscopy services is growing inexorably and diverse strategies have been proposed to use them more effectively [1,8]. One suggestion has been centred around the close association between Helicobacter pylori and peptic ulcers and the development of accurate serological tests for the presence of this organism. This could allow endoscopy to be targetted to patients serologically positive for H. pylori, among whom nearly all peptic ulcers should occur. We have examined the likely results of implementing three different strategies for easing endoscopic workload, using retrospective data from dyspepsia clinics.

Editor,—The Maastricht Consensus Report ( Gut 1997; 41 :8–13) is a welcome benchmark summarising current opinion and scientific evidence regarding the role of Helicobacter pylori in gastroduodenal disorders. Whereas the management of peptic ulcer disease is no longer controversial and is very evidence-based the same is not yet true for the syndrome of non-ulcer dyspepsia and the management of the uninvestigated dyspeptic patient. The recommendation of the Maastricht Report reflects this uncertainty. They recommend that at the specialist level, eradication therapy for H pylori infected non-ulcer dyspepsia is “advisable”, based on supportive scientific evidence, but only after “full investigation” including endoscopy, ultrasound and other tests. However, in the management algorithm for the uninvestigated dyspeptic in primary care, non-invasive testing (with a breath test) and treatment is recommended for patients who are at a low risk of gastric carcinoma. Why such a difference? If it is recommended that a breath test is investigation enough of dyspepsia in primary care then an endoscopy and biopsy should be adequate in specialist practice if there are no other clinical indicators of another diagnosis (such as biliary colic) and the patient is at low risk of malignancy. The difficulty is that non-ulcer dyspepsia will remain a hard target and even several studies of symptom response after eradication therapy due to be reported shortly will not resolve the issues as there will be perennial debate about inclusion and exclusion criteria in such trials and these will have a great bearing on outcomes. Moreover, the ability to quantitate the lifetime risk reduction of peptic ulcer disease and perhaps even gastric carcinoma in patients who have eradication therapy will remain contentious. Medico-legal issues and patient preferences will also continue to be important factors influencing the decision to investigate and treat. At present the suggested test and treat …

The long-term effect of prednisone in Crohn's disease has been examined in a double-blind controlled trial. Clinical relapse, recurrence, and extension of the disease were examined in 64 patients followed-up for up to three years. Fourteen patients were withdrawn because of severe symptoms (eight on prednisone and six controls); the withdrawal rate in both groups was 30% at three years. Nine other patients had radiological recurrence or extension of disease (five prednisone and four controls). Prednisone did not improve the relapse rate, nor did it affect recurrence or extension of disease.

SummaryA wide range of nutritional disturbances may be found in patients with Crohn’s disease. As more sophisticated tests become available to measure vitamin and trace element deficiencies, so these are being recognized as complications of Crohn’s disease. It is important to recognize nutritional deficiencies at an early stage and initiate appropriate treatment. Otherwise many patients, experiencing what can be a chronic and debilitating illness, may suffer unnecessarily from the consequences of deprivation of vital nutrients.

T-cell subsets and their activation state were examined by double-label immunofluorescence of cryostat tissue sections of the colon from 21 patients with ulcerative colitis (UC) and 30 histologically normal controls. Expression of MHC class I (HLA-A, B, C) and class II (HLA-D) antigens was studied in parallel. In the normal colonic mucosa, the CD4:CD8 ratio in the epithelial compartment approximated 1:1, and in the lamina propria, 2.55:1. Of the CD8+ (cytotoxic/suppressor) subset, approximately half did not express the CD5 "pan-T" marker in either compartment. Virtually no Leu8+ cells were observed, implying that the CD4+ subset consisted of helper, rather than suppressor-inducer cells. Classical markers of T-cell activation (CD25, HLA-D) and proliferation were absent, and strong expression of the CD7 "immunostimulation" marker was approximately equal in both CD4 and CD8 subsets. The epithelium was uniformly negative for class II antigens, but positive for class I. In UC, there were no significant alterations in CD4:CD8 ratios in either compartment, and there were no changes with respect to phenotype of the subsets. In 11 of 19 patients (mainly with total colitis), enterocytes were HLA-D+. In this HLA-D+ group, there was an increase in the percentage of CD4+ cells coexpressing CD7; this difference was significant (P less than 0.02) in the lamina propria. Increased expression of CD7 was also found by the CD6+ T cell subset (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Nutrient depletion is a common complication of inflammatory bowel disease, and some of the consequences can be severe. Although it is often easy to recognise the most severely undernourished subjects, those with lesser degrees of malnutrition may prove more difficult to detect. Measurements of many nutritional variables will be abnormal in patients with inflammatory bowel disease, especially in those with Crohn's disease, but are not always relevant to the clinical management of patients. Anthropometric means of assessment, in particular, measurement of mid arm circumference, can act as a simple, reproducible method of detecting those most at risk of appreciable undernutrition.

The effect of topical disodium cromoglycate (DSCG) has been examined in 30 patients with chronic active proctitis using a double-blind crossover trial. Each treatment period was four weeks and patients were given DSCG 200 mg by enema twice daily and 100 mg orally three times each day. Twenty-six patients completed the trial successfully, 14 responded to DSCG treatment, two improved with placebo, and 10 responded to neither. Patients who responded to DSCG had significantly more eosinophils in their rectal biopsies than those who failed to respond and in some instances the counts were very high. The findings support the hypothesis than an allergic reaction is important in the pathogenesis of proctitis.

Biopsy specimens of gastric and duodenal mucosa from 290 patients were examined histologically for metaplasia and Campylobacter pyloridis. Estimates of pH on samples of fasting gastric juice from 55 of the patients were performed, and mucosal biopsy specimens from 33 patients were also cultured for C pyloridis. Active duodenitis was seen in 34 duodenal biopsy specimens. Thirty (88%) of the patients with active duodenitis had both greater than 5% gastric metaplasia in the duodenal specimen and C pyloridis associated gastritis. These two factors coexisted in only 0.43% of patients with no duodenal inflammation. When C pyloridis were seen histologically in duodenal biopsy specimens they were confined to areas of gastric metaplasia and never occurred in the absence of a polymorph infiltrate. Of the 55 patients with measurements of gastric juice pH, gastric metaplasia was present in the duodenum in 20 of 42 with a pH of less than 2.5, and in 0 of 13 with a pH of greater than 2.5. These results suggest that acid induced gastric metaplasia in the duodenum and C pyloridis associated gastritis may be synergistic in the pathogenesis of duodenitis; the metaplastic gastric epithelium allows C pyloridis to colonise the duodenal mucosa, where it produces an acute inflammatory response.

The influence of Peyer's patches (PP) on the selective localization of proliferating mesenteric lymph node (MLN) cells in the small intestine was studied in syngeneic rats using an adoptive transfer method. Within 24 h after transfer, 125 I-deoxyuridine-labeled cells from donor MLN showed equivalent localization in recipient intestines either surgically ablated of PP or subjected to a sham surgical procedure 3 wk previously. No alteration in this localization was noted if the surgery was performed 14 wk prior to cell transfer. We conclude that PP do not play an essential role in the entry of MLN lymphoblasts into the small intestine.

One hundred and sixty patients have been studied to assess the significance of circulating antigen-antibody complexes in inflammatory bowel disease (IBD). Sera from patients with ulcerative colitis and Crohn's disease were assayed for Clq-binding antigen-antibody complexes (CIC) and the results compared with those obtained from 52 patients with other inflammatory gastrointestinal diseases (GI controls) and 26 normal volunteers (normal controls). Significantly elevated CIC levels were found in patients with active IBD compared with inactive IBD or normal controls. However, similar high levels were also found in the GI control group. CIC levels in a group of undernourished patients with Crohn's disease fell significantly after treatment with an oral nutritional supplement. The results suggest that CIC-mediated inflammation is likely to be associated with intestinal mucosal disease in a non-specific manner.

Vagal function in 28 patients with gastro-oesophageal reflux was examined by determining gastric secretory response to insulin-induced hypoglycaemia and pulse-rate variation with respiration. Gastric secretory studies were also performed on 13 patients with duodenal ulcer who had not undergone operations. In all patients the presence and degree of oesophagitis were determined endoscopically and mucosal biopsy and oesophageal manometry were performed. Seven of the 28 patients with gastro-oesophageal reflux showed evidence of impaired vagal efferent function in the upper alimentary tract. No such impairment was found in those patients who showed manometric evidence of oesophageal spasm secondary to gastro-oesophageal reflux. Low pulse-rate variation with respiration was found in 12 of 27 patients with gastro-oesophageal reflux, suggesting dysfunction of cardiac vagal fibres. Impairment of efferent vagal supply may be a causative factor in some patients with gastr-oesophageal reflux but does not seem to be important in oesophageal spasm secondary to gastro-oesophageal reflux.

Une observation rare: malade de 75 ans presentant un petit hematome sous-dural dans la region fronto-temporale gauche;. Les seules manifestations cliniques sont des crises epileptiques variees: convulsions, absences, confusion mentale etc.

The organism that we now know as Campylobacter pylori was first isolated in 1982 by Marshall et al. [1] in Australia. The organism had, however, been intermittently noted on gastric epithelium by a variety of investigators in several countries since the turn of the century.

The stomach and upper gut are normally sterile with only transient flora appearing following ingestion of food. The gastric defences including acid, mucus, lysozyme and immunoglobulins protect the upper gut from bacterial colonization. With decreasing gastric acidity, which occurs normally with ageing and with conditions such as pernicious anaemia and following gastric surgery, the stomach may become colonized with faecal as well as oral bacteria1. Patients with hypochlorhydria are also more susceptible to enteric infections such as cholera and salmonellosis2.

In normal rabbits, lymphocytes have been identified in large numbers on the luminal epithelial aspects of both Peyer's patches and the appendix by scanning and transmission electron microscopy. Luminal cells shared an intimate relationship with intestinal microorganisms. Irrigation of the appendiceal lumen has proved a useful technique for collecting 8.5 x 10(6) (mean) viable lymphocytes (73%) and macrophages (22%). Functional characteristics (mitogen responsiveness, T-cell numbers and cells with positive cytoplasmic immunoglobulin A fluorescence) were similar to isolated intestinal mucosal cell preparations. In vivo cytokinetic studies indicated that 50% of luminal appendiceal lymphocytes were recently divided (within 5 h). The passage of lymphoid cells into the the appendix lumen was antigen responsive, as was the size of the appendiceal lymphoid mass. This evidence suggests that migration of lymphoid cells into the lumen of the intestine in healthy animals occurs normally probably from the gut-associated lymphoid tissue--a phenomenon similar to that observed in the bronchial tract. Both mucosal surfaces may, therefore, be important sites of lymphocyte and macrophage traffic.

An orally absorbed mast cell stabiliser (BRL-10833) has been compared with placebo in a double-blind controlled trial in twenty-five patients with ulcerative colitis; patients received each treatment for one month. There was no significant clinical improvement in symptoms or sigmoidoscopic findings with the drug but there was significant improvement in the histological appearance of rectal biopsies during active treatment.

One-hundred-and-thirteen rectal biopsies and 17 total colectomy specimens from 50 patients with ulcerative proctocolitis were examined. These patients had been followed for periods up to 220 months, mean 70 months. The histological changes were compared with the clinical features of the disease. Patients with relatively benign disease which responded to treatment had significantly raised eosinophil counts in the mucosa examined, compared with patients who had aggressive disease which failed to respond to medical treatment (P less than 0.001). Tissue eosinophilia in the rectal mucosa may provide a simple method for predicting the clinical course of patients with ulcerative proctocolitis.

Normal human colonic lymphocyte populations were isolated for both phenotypic analysis by double-label immunofluorescence and assessment for regulatory effects on Ig production by co-culture with responder cells from colonic mucosa and peripheral blood. Mean CD4:CD8 ratios for colonic intraepithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL) were comparable to values obtained from tissue sections. IEL alone did not produce Ig in vitro and were without effect on Ig production when co-cultured with LPL. However, T-enriched LPL had a marked helper effect for T-depleted LPL. Maximal help was for IgA production, increasing with numbers of T-enriched cells. In colonic LPL T-depleted and T-enriched co-cultures, pokeweed mitogen (PWM) had no significant effect. By contrast, in co-cultures of T-enriched and T-depleted peripheral blood mononuclear cells, Ig production was PWM-dependent. In all experiments with colonic mucosal responder cells, IgG production was low. The effects of unfractionated colonic biopsy lymphocytes on T-depleted peripheral blood mononuclear cells were additive for IgM production and synergistic for IgA synthesis, although almost no IgG was produced. Moreover, PWM had helper effects for IgM, but was suppressive for IgA production. These data suggest that colonic mucosal regulatory cells reside in the lamina propria, and predominantly provide help for IgA and IgM synthesis. The data further suggest the existence of a pre-stimulated IgA-specific T helper cell population.

The exact pathogenic mechanisms involved in Campylobacter pylori associated gastro-duodenal inflammation are unclear. C. pylori adheres to gastric type epithelium and colonisation is associated with a number of ultrastructural abnormalities. Other factors thought important include the marked bacterial urease activity, enzymatic degradation of the mucous layer and possible toxins. The induced inflammatory reaction will also contribute to tissue damage and a breakdown of normal defense mechanisms.