Referral patterns to a district general hospital gastroenterology outpatient clinic: implications for the 'two-week target'.

We defined the pattern and appropriateness of GPs' new-patient referrals to a large district general hospital gastroenterology department, and assessed the implications for workload in the context of the recently introduced 'two-week target'. Prospective data were collected on all new referrals over a two-month period and 426 new appointments were included, from which data were available on 390. Only six referrals were deemed inappropriate. Sixty-nine patients had a functional disorder, and GPs were less likely to diagnose this group at referral than the gastroenterologist was after the initial consultation. Nineteen per cent of all GP referrals were classified as urgent and 6% of these had a malignancy. Fifty per cent of patients with malignancy were not perceived as meriting an urgent referral by the GP Gastroenterology outpatient facilities are already overstretched and the implementation of the two-week target will add considerable strain to the current resources, with little gain in identifying malignancy.

Gastroduodenal mucosal vitamin-C levels in Helicobacter pylori infection.

BACKGROUND: Vitamin C is an important endogenous antioxidant, and epidemiologic evidence suggests that it may protect against the development of gastric cancer. We therefore determined mucosal vitamin-C levels in the stomach and duodenum of subjects with and without Helicobacter pylori infection. METHODS: The patients were 30 subjects undergoing routine gastroscopy for investigation of dyspepsia. High-performance liquid chromatography with electrochemical detection was used to determine mucosal ascorbic acid and total vitamin-C levels. RESULTS: In H. pylori-negative subjects with normal gastroduodenal histology the antrum contained significantly higher levels of ascorbic acid and total vitamin C than the corpus or duodenum (P < 0.05). No significant changes were seen in gastric mucosal ascorbic acid or total vitamin-C levels in the presence of H. pylori infection and related inflammation. The presence of gastric atrophy did not affect mucosal ascorbic acid or total vitamin C levels. Duodenal ascorbic acid and total vitamin-C levels did not change significantly in the presence of gastric H. pylori or duodenal inflammation. CONCLUSIONS: Although high levels of vitamin C are present in the gastroduodenal mucosa, these are not altered in the presence of H. pylori infection and inflammation. These observations suggest that the mucosal antioxidant potential of vitamin C is not impaired by H. pylori infection.

The management of young dyspeptic patients in the era of Helicobacter pylori.

The management of young dyspeptic patients remains controversial in the modern Helicobacter pylori era. The use of non-invasive screening for H. pylori in one proposed strategy has demonstrated a substantial reduction in the endoscopy workload by excluding H. pylori negative patients under the age of 45 years with uncomplicated dyspepsia. An alternative screening strategy proposes a 'test and treat' approach, with H. pylori positive patients proceeding directly to an empirical course of eradication therapy. Ednoscopy would be reserved for patients who failed to respond symptomatically or who were H. pylori negative on intial screening. At present there are few data available from clinical studies of putting the 'test and treat' policy into practice. Although there is likely to be a role for screening young dyspeptic patients for H. pylori in primary care, subsequent management requires well-planned studies in order to assess the benefits of any particular strategy.

Bone mineral density in patients with inflammatory bowel disease.

BACKGROUND: Studies have shown an association between inflammatory bowel disease (IBD) and low bone density. Previous publications, however, measured only a single parameter, either T or Z score, making comparison of data difficult. OBJECTIVE: To assess the effect of disease factors on both T and Z scores in a population of patients with IBD. METHODS: Risk factors for development of low bone density were recorded in IBD patients with confirmed diagnosis and disease extent. Bone density was then measured at the spine and neck of femur using dual-energy X-ray absorptiometry. RESULTS: Ninety-one patients (49 male, 42 female) with a mean age of 46.6 years (range 22-84) were studied. Forty-eight patients had ulcerative colitis and 43 had Crohn's disease. Mean Z scores were -0.60 at the hip and -0.61 at the spine, whilst mean T scores were - 1.61 at the hip and -1.15 at the spine. Univariate analysis of Z scores identified Crohn's disease, high steroid use and low BMI as significantly associated with low bone density. An identical analysis using T scores failed to show any significant relationships. On multivariate analysis of Z scores, only disease type and BMI remained significant. CONCLUSIONS: Low bone density is associated with IBD particularly in patients with Crohn's disease and low BMI. This large UK study is the first to report both T and Z scores in patients with IBD and shows that Z scores are the most reliable guide to the effect of IBD on bone density.

Plasma free radical activity and antioxidant vitamin levels in dyspeptic patients: correlation with smoking and Helicobacter pylori infection.

BACKGROUND: The pathological processes by which Helicobacter pylori infection leads to the development of gastroduodenal disease are still incompletely understood. Oxygen-derived free radicals are important mediators of inflammation and potential carcinogens. Furthermore, dietary studies have suggested that antioxidant vitamins may protect against gastric cancer. OBJECTIVE: To determine plasma free radical activity and antioxidant vitamin levels in dyspeptic patients and to correlate the results with H. pylori infection and tobacco smoking. SUBJECTS: Forty-three patients undergoing routine endoscopy for investigation of dyspepsia. METHODS: Plasma free radical activity was determined by measurement of thiobarbituric acid-reactive substances (TBARS). Plasma samples were also assayed for the antioxidant vitamins A, C and E. Gastroduodenal biopsies were obtained from all patients for histological examination. RESULTS: Plasma TBARS levels were significantly higher in H. pylori positive versus negative subjects (P < 0.03), smokers versus non-smokers (P < 0.04) and males versus females (P < 0.01). Multiple regression analysis revealed that after correcting for male sex and smoking there was no significant association between plasma free radical activity and H. pylori infection. Smokers had significantly lower levels of plasma vitamin C than non-smokers (P< 0.05); no differences were seen in vitamin A and E levels. Gender and H. pylori infection did not significantly affect plasma antioxidant vitamin levels. Gastroduodenal disease was present in all of the smokers compared with 67% of the non-smokers (P < 0.05); 69% of the smokers were H. pylori positive versus 53% of the non-smokers. CONCLUSIONS: Tobacco smoking and male sex, both recognized risk factors for gastroduodenal disease, appear to be the major determinants of increased plasma free radical activity in dyspeptic subjects, rather than H. pylori infection. The reason for the higher prevalence of H. pylori infection and gastroduodenal disease in dyspeptic smokers is unclear but may relate to weakened antioxidant defences.

Peanut ingestion increases rectal proliferation in individuals with mucosal expression of peanut lectin receptor.

BACKGROUND & AIMS: The Thomsen-Friedenreich blood group antigen (galactose beta 1,3-N-acetyl galactosamine alpha-) acts as an oncofetal antigen in the colonic epithelium, with low expression in normal adult epithelia but increasing to fetal levels of expression in hyperplasia or malignancy. Peanut lectin is one of the commonest dietary lectins that binds this antigen. The aim of this study was to determine whether peanut ingestion can alter rectal epithelial proliferation. METHODS: Thirty-six patients with normal colonic mucosa consumed 100 g of peanuts each day for 5 days. Rectal mitotic index was measured before and after ingestion, and changes in proliferation were correlated with immunohistochemical detection of lectin receptor expression by colonocytes and fecal lectin activity as measured by hemagglutination assay. RESULTS: Peanut ingestion caused a 41% increase in rectal mucosal proliferation in individuals with macroscopically normal mucosa who express TF antigen in their rectal mucosae (10 of 36 patients studied). The proliferative response correlated with fecal hemagglutinating activity, and peanut lectin could be shown immunohistochemically within the rectal mucosa. CONCLUSIONS: The common expression of galactose beta 1,3-N-acetyl galactosamine alpha- by hyperplastic and neoplastic epithelia may therefore be functionally important because it allows interaction with mitogenic dietary lectins. This could be an important mechanism for the association between diet and colorectal cancer.

Recurrence of duodenal ulcer after Helicobacter pylori eradication is related to high acid output.

BACKGROUND: Helicobacter pylori eradication reduces the recurrence of duodenal ulcers. It is unclear why duodenal ulcers rarely recur in the absence of reinfection with H. pylori or NSAID treatment. METHODS: Basal, gastrin-releasing peptide- and pentagastrin-stimulated peak acid outputs in patients with ulcer relapse after H. pylori eradication were measured, and compared with patients without ulcer relapse after H. pylori eradication. RESULTS: Pentagastrin-stimulated peak acid output was significantly higher in H. pylori-positive patients with duodenal ulcers than in H. pylori-negative controls, and fell significantly after H. pylori eradication. In H. pylori-negative patients with recurrent duodenal ulcers, pentagastrin-stimulated peak acid output was significantly higher than in controls and similar to H. pylori-positive patients with duodenal ulcers. CONCLUSIONS: These findings suggest that duodenal ulcer relapse after eradication of H. pylori may be related to high pentagastrin-stimulated peak acid output. In this subset of patients with duodenal ulcers, maintenance anti-secretory treatment may be necessary to prevent relapse.

Lansoprazole plus clarithromycin: evaluation of a new dual therapy for Helicobacter pylori eradication.

The aim of this pilot study was to evaluate the efficacy and safety of lansoprazole plus clarithromycin for eradication of Helicobacter pylori. A total of 26 patients with H. pylori infection were randomised to receive clarithromycin, 500 mg t.i.d. for 14 days, plus either lansoprazole, 30 mg o.m., (group L30, n = 13) or lansoprazole, 30 mg b.i.d., (group L60, n = 13). H. pylori status was determined pre-treatment and four to six weeks after completion of the study medication by histology and 13C-urea breath test. Two patients were unable to complete the course of medication. Of the remaining 24 patients, 14 (58%) successfully eradicated H. pylori--8/12 (67%) patients in group L30 and 6/12 (50%) in group L60. Side-effects were experienced by 17/26 (65%) of patients, most commonly a taste disturbance. The results from this pilot study suggest that dual therapy with lansoprazole plus clarithromycin is only a moderately effective regimen for eradicating H. pylori.

Vitamin E concentrations in the human stomach and duodenum--correlation with Helicobacter pylori infection.

BACKGROUND: Vitamin E (alpha-tocopherol) is an important endogenous antioxidant and may also act as an anticarcinogen. AIM: To determine the vitamin E status of subjects with, and without, gastroduodenal inflammation and Helicobacter pylori infection. SUBJECTS: 36 patients undergoing routine gastroscopy for investigation of dyspepsia. METHODS: High performance liquid chromatography with fluorometric detection was used to determine alpha-tocopherol values. RESULTS: In H pylori negative subjects with normal gastroduodenal histology (n = 11) median alpha-tocopherol values (ng/mg tissue weight) were significantly higher in the corpus (16.4, interquartile range (IQR) 8.9-22.6) than in the antrum (3.0, IQR 2.6-6.7, p = 0.001) or duodenum (6.7, IQR 2.5-8.4, p = 0.001). H pylori infection (n = 19) was associated with a reduction in the corpus alpha-tocopherol values (median 8.3, IQR 4.9-13.7, p < 0.05) but there was no significant change in the antral concentrations although this was the main site of inflammation and neutrophil activity. Duodenal alpha-tocopherol values were not significantly changed in the presence of duodenitis or gastric H pylori infection. alpha-Tocopherol was not detected in the gastric juice of any of the subjects. Plasma alpha-tocopherol concentrations in the H pylori negative subjects (median 10.4 mg/l, IQR 7.2-11.9) were not significantly different to the values in the H pylori positive subjects (median 11.1 mg/l, IQR 7.6-12.7). CONCLUSIONS: Concentrations of alpha-tocopherol in H pylori negative subjects are higher in the corpus than in the antrum or duodenum. In the presence of predominantly antral H pylori infection and neutrophil activity the major change seen is a reduction in corpus alpha-tocopherol values while antral concentrations are maintained. These findings may reflect a mobilisation of antioxidant defences to the sites of maximal inflammation in the stomach.

Histology of chronic gastritis with and without duodenitis in patients with Helicobacter pylori infection.

AIM: To compare the histological characteristics of Helicobacter pylori positive chronic gastritis in patients with and without associated duodenitis. METHODS: Gastric mucosal biopsy specimens were obtained from patients undergoing endoscopy for dyspepsia. Severity of gastritis and density of H pylori infection were graded according to the Sydney system. RESULTS: Of the 69 patients studied, 15 had normal histology, 22 had chronic gastritis only (77.3% H pylori positive), 21 had duodenitis (90.5% H pylori positive), and 11 had other diagnoses. In the H pylori positive patients, the median gastritis score was higher in the duodenitis group (6, range 3-9) than in the chronic gastritis only group (5, range 2-8), because of greater neutrophil activity scores in patients with duodenitis (median score 2 v 1). There were no differences in the density of H pylori infection, inflammation, atrophy, or intestinal metaplasia between patients with chronic gastritis only and those with duodenitis. CONCLUSIONS: These results suggest that H pylori positive patients with duodenitis have a more severe form of gastritis than those without associated duodenal inflammation. This is because of increased neutrophil activity, which seems to be independent of the density of H pylori infection.

One week treatment for Helicobacter pylori infection: a randomised study of quadruple therapy versus triple therapy.

This study evaluated one week of quadruple therapy as treatment for Helicobacter pylori infection. Sixty duodenal ulcer patients were randomised to receive either standard triple therapy (tripotassium dicitrato bismuthate 120 mg qds+tetracycline 500 mg qds+metronidazole 400 mg qds), quadruple therapy A (triple therapy+omeprazole 20 mg od) or quadruple therapy B (triple therapy+omeprazole 40 mg od), for 7 days. H. pylori eradication rates were 65%, 60% and 60%, respectively, with no significant differences between the groups. These results suggest that quadruple therapy provides no benefits over one week of triple therapy for treatment of H. pylori infection.

The economic and quality-of-life benefits of Helicobacter pylori eradication in chronic duodenal ulcer disease--a community-based study.

A policy of Helicobacter pylori eradication in patients with duodenal ulceration on long-term acid-suppressing therapy was evaluated in a prospective study amongst a general practice population, with particular reference to economic and quality-of-life benefits. One hundred and sixty-eight patients on long-term acid-suppressing therapy had chronic duodenal ulcer disease of whom 88 were eligible for the study; 45 patients attended for review, with 42 testing positive for H pylori (as assessed by 13C-urea breath test). The median duration of acid-suppressing therapy was six years (maximum 15 years); 47.6% of the patients were using additional antacids and 80.9% still experienced epigastric discomfort. Two-thirds (28/42) of the patients eradicated H pylori. Successful eradication was associated with a highly significant reduction in all symptoms. At 12 months follow-up, heartburn had decreased from 28.7% to 7.1%, epigastric discomfort from 75% to 3.6%, nausea from 32.1% to 0% and wind from 50% to 0%. Of the patients that eradicated H pylori 96.4% reported an improvement in their general health compared to none of those that remained H pylori positive. Successful H pylori eradication therapy scored higher on satisfaction ratings than long-term acid-suppressing therapy. Eradication of H pylori resulted in 27/28 patients being able to discontinue acid-suppressing therapy, representing a 5.8% reduction in the use of such drugs per year in the local general practice population. A policy of H pylori eradication in chronic duodenal ulcer disease reduces the use of long-term acid-suppression therapy in general practice. This has important financial implications as well as offering considerable symptomatic benefits to the patients and improving their quality of life.

Dual-centre, double-blind, randomised trial of lymphoblastoid interferon alpha with or without steroid pretreatment in children with chronic hepatitis B.

Thirty-five children with chronic HBV infection, HBV-DNA and eAg serum positivity, and HBcAg in liver tissue were treated with lymphoblastoid human interferon alpha with (16 cases) or without (19 cases) prednisolone pretreatment. The patients were double-blind randomized to receive steroid or placebo for 4 weeks, followed after 2 weeks by 5 or 10 MU/m2 interferon for 12 weeks. The e anti-e seroconversion rate reached 48%, which is much higher than the spontaneous seroconversion rate. The influence of "prednisolone priming" was not statistically significant. HBeAg clearance was similar in both groups (44% after prednisolone/interferon and 53% after interferon alone). The response to either treatment did not correlate with the pretreatment serum transaminase. HBV-DNA or degree of histological activity. Interferon was well tolerated, the side effects being less severe than in adults, and never led to suspension of the treatment.

A radical view of the stomach: the role of oxygen-derived free radicals and anti-oxidants in gastroduodenal disease.

Following the discovery of Helicobacter pylori, the last decade has seen major advances in our understanding of gastroduodenal disease. However, our knowledge remains incomplete and the exact mechanism by which H. pylori causes inflammation and ulceration is still not known. The role of H. pylori in relation to other well known risk factors for gastroduodenal disease such as diet, smoking and the use of non-steroidal anti-inflammatory drugs is also unclear. Free radicals are highly toxic chemical species and evidence presented in this review suggests that they play an important role in the pathophysiology of gastroduodenal disease caused by many risk factors, including H. pylori. Dietary antioxidant deficiency may be a major factor in the development of gastric cancer and may exacerbate the carcinogenesis of nitrosamines. Antioxidant deficiency, either dietary or secondary to increased requirements as in smoking, may be a factor in the development of disease following H. pylori infection. The time now appears to be ripe for studies of novel antioxidant therapeutic strategies for gastroduodenal disease.

Long term acid suppressing treatment in general practice.

OBJECTIVE: To determine the current practice in selected general practices for prescribing long term (> 6 months) treatment to suppress gastric acid secretion. SETTING: Seven general practices in the Harrow area that always or usually refer to Northwick Park Hospital. SUBJECTS: 60,148 patients on lists of the general practices. DESIGN: Identification of patients receiving long term treatment through repeat prescribing data, followed by a manual and computer survey of patients' notes for indications and investigations. Patient compliance and views on treatment were sought by a postal questionnaire. MAIN OUTCOME MEASURES: Indications for treatment, treatment given, investigations undertaken before and during treatment. RESULTS: 492 patients (0.82% of the population) were taking long term acid suppressing treatment. The most common diagnosis was duodenal ulcer disease (183 (37%) of all patients); oesophageal disease (118 (24%)) was also common. 93 patients (19%) were treated for abdominal pain where no diagnosis had been reached or who had only a diagnosis of gastritis on endoscopy. Ranitidine was prescribed in 394 (80%) patients. 298 (74%) patients found treatment helpful, but 108 (27%) had a poor understanding of their diagnosis. 317 patients (78%) took their drug as prescribed. 37 patients were also taking prescribed non-steroidal anti-inflammatory drugs and an additional 43 patients took regular aspirin or ibuprofen without prescription. CONCLUSIONS: Long term acid suppressing treatment is common, and a substantial number of patients are taking these drugs long term without a diagnosis having been reached. It is hoped that protocols for investigation and treatment will improve these figures. Patients need to be better informed about their disease and the possible adverse effects of taking non-steroidal anti-inflammatory drugs in acid related upper gastrointestinal disease.