Intestinal permeability and morphometric recovery in coeliac disease.
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Carbohydrates↗
Biomedical subjects
R G Watson
Publications and source records attributed to R G Watson.
Flexible sigmoidoscopy and the changing distribution of colorectal cancer: implications for screening.
BACKGROUND AND AIMS: There has been a significant proximal shift in the distribution of colorectal cancer (CRC) in Northern Ireland over recent decades. The aim of this study was to investigate the potential implications of this proximal shift in CRC distribution on the efficacy of flexible sigmoidoscopy (FS) as a screening tool. PATIENTS AND METHODS: The site distribution of 5153 CRCs was available from the Northern Ireland Colorectal Cancer Register for the period 1990-1997. Similar data on 1241 CRCs between 1976 and 1978 were available from a previous study. Data on the site reached by FS were obtained from a prospectively collected endoscopy database at one of Northern Ireland's main teaching hospitals for the period 1993-1998. RESULTS: There was a significant proximal shift in CRC distribution between the two periods (23.5% proximal to the splenic flexure between 1976 and 1978 v 36.7% between 1990 and 1997; p<0.001). The descending colon was visualised during 74.4% of FS examinations. By combining the observed extent of FS examination with CRC site distribution, it was calculated that FS could have visualised 68.8% of CRCs between 1976 and 1978 but only 56.0% between 1990 and 1997. Extrapolating these data to a Northern Ireland screening programme involving FS and faecal occult blood testing suggests that significantly more CRCs could have been detected between 1976 and 1978 than between 1990 and 1997 (51.7% v 48.2%, respectively; p=0.03). CONCLUSIONS: This study confirms the previously documented left to right shift in CRC distribution in Northern Ireland and demonstrates that if this shift continues, FS will become less successful as a screening tool than is currently predicted.
Colorectal Neoplasms↗
Treatment of intestinal Behçet's syndrome with chimeric tumour necrosis factor alpha antibody.
Few patients with Behçet's syndrome have gastrointestinal ulceration. Such patients are difficult to treat and have a higher mortality. Faced with refractory symptoms in two patients with intestinal Behçet's, we used the tumour necrosis factor alpha (TNF-alpha) monoclonal antibody infliximab to induce remission. Both women (one aged 27 years, the other 30 years) presented with orogenital ulceration, pustular rash, abdominal pain, bloody diarrhoea due to colonic ulceration, weight loss, and synovitis. One had thrombophlebitis, digital vasculitis, perianal fistula, and paracolic abscess; the other had conjunctivitis and an ulcer in the natal cleft. Treatment with prednisolone, methyl prednisolone, and thalidomide in one and prednisolone, colchicine, and cyclosporin in the other was ineffective. After full discussion, infliximab (3 mg/kg, dose reduced because of recent sepsis in one, and 5 mg/kg in the other) was administered. Within 10 days the ulcers healed, with resolution of bloody diarrhoea and all extraintestinal manifestations. A second infusion of infliximab was necessary eight weeks later in one case, followed by sustained (>15 months) remission on low dose thalidomide. Remission was initially sustained for 12 months in the other but thalidomide had to be stopped due to intolerance, and a good response to retreatment lasted only 12 weeks without immunosuppression, before a third infusion. The cause of Behçet's syndrome is unknown but peripheral blood CD45 gammadelta T cells in Behçet's produce >50-fold more TNF-alpha than controls when stimulated with phorbol myristate acetate and anti-CD3. Infliximab could have a role for inducing remission in Behçet's syndrome.
Adult↗
Small bowel lymphoma in unrecognized coeliac disease: a cause for concern?
BACKGROUND AND AIM: It is not clear whether the increased risk of small bowel lymphoma seen in typical coeliac disease also applies to unrecognized or screening-detected coeliac patients. The aim of the present study was to determine the features of small bowel lymphoma and whether it is associated with unrecognized coeliac disease at the time of presentation. DESIGN: A retrospective search by the five pathology laboratories serving Northern Ireland, UK. METHODS: Snomed searches were used to identify cases of adenocarcinoma (SBA) and lymphoma (SBL) affecting the small intestine between 1987 and 1996. Pathology reports were obtained and analysed with respect to the clinical features, site of pathology, type of tumour, grading and the presence or absence of distant villous atrophy. RESULTS: One hundred and thirty-eight cases were identified of whom 69 (44 men; mean age 60.2 years) were SBL and 69 (41 men; mean age 68.0 years) were SBA. Comparing the SBL to the SBA group the clinical presentation was perforation (10 vs 1, P= 0.009), small intestinal obstruction (20 vs 20, P= 1.0) and small intestinal mass (13 vs 15, P= 0.67). B-cell lymphomas occurred in 20 cases, T-cell lymphomas in 24 cases and 25 were unclassified. There was one known coeliac patient in the SBL group and none in the SBA group (P = 1.0). Villous atrophy at a distant site was recorded in 13 patients in the SBL group compared to none in the SBA group, all of these patients having T-cell lymphomas. CONCLUSIONS: Similar numbers of SBL and SBA occurred in the study period. Their clinical presentation was similar although perforation was more common in the SBL group. One-third of all SBL patients (over half of T-cell lymphomas) had distant villous atrophy, indicating that small bowel lymphoma appears to be significantly associated with unrecognized coeliac disease.
Adenocarcinoma↗
The effect of lifestyle changes on results of 24-h ambulatory oesophageal pH monitoring.
OBJECTIVES: Twenty-four-hour pH monitoring is the 'gold standard' investigation of gastro-oesophageal reflux disease. It has been suggested that results may be influenced by lifestyle alteration during the study. The aim of this study was to determine the influence of lifestyle alteration and anxiety on outcome in pH monitoring. METHODS: One hundred consecutive patients attending for pH monitoring were recruited. Post-intubation anxiety was quantified (STAI form Y-1). On completion a questionnaire was recorded comprising six questions regarding alteration to eating/drinking (FOOD) (score 0-6) and six regarding posture and activity (ACTIVITY) (score 0-6). The higher the score the greater the alteration of lifestyle. A 10-point visual analogue scale (VAS) scored the degree of distress caused by the experience. pH studies were positive if exposure times at pH < 4 were greater than established normal values or if the Symptom Index was > 50%. Comparisons were made between patients with positive and negative studies regarding FOOD, ACTIVITY, VAS and STAI scores. RESULTS: Patients with positive pH studies had mean FOOD (2 vs 2; P> 0.05), ACTIVITY (2 vs 2; P> 0.05), VAS (3 vs 3; P> 0.05) and STAI (31 vs 32; P> 0.05) scores which were not significantly different from those of patients with negative pH studies. CONCLUSIONS: Lifestyle alteration was minimal in patients undergoing pH monitoring, nor was the experience distressing. There was no difference in lifestyle alteration and anxiety between those with positive and negative pH profiles.
Adolescent↗
Lactulose-mannitol intestinal permeability test: a useful screening test for adult coeliac disease.
The aim of this study was to determine the value of the lactulose mannitol intestinal permeability test in screening the general adult population for unrecognized enteropathy and latent coeliac disease. Subjects with positive serology (identified by screening carried out by the Belfast MONICA Project) along with controls were followed-up after 3 years and classified as having transient serology, persistent serology or coeliac disease. A 5-h urine collection was performed following the ingestion of 5 g lactulose, 2 g mannitol and glucose as an osmotic filler. Urinary concentrations of lactulose and mannitol were measured by enzymatic analysis. Percentage lactulose excretion (%LE) (0.94 versus 0.31, P<0.001) and lactulose mannitol excretion ratio (LMER) (0.12 versus 0.02, P<0.001) were significantly higher in screening-detected coeliac disease subjects compared with MONICA controls. The sensitivity of the permeability test was 87% in the screening situation compared with 81% in the clinical situation. In subjects with persistent and transient serology the LMER did not differ significantly from that of controls. The lactulose-mannitol test is a useful test for screening the general adult population for coeliac disease. Subjects with persistent and transient serology did not differ from MONICA controls and are unlikely to have latent coeliac disease.
Adult↗
Genetic, morphometric and immunohistochemical markers of latent coeliac disease.
BACKGROUND: It is recognized that coeliac disease may exist in a latent form characterized by HLA-DR3 and increased counts of intra-epithelial lymphocytes (IELs) and gamma/delta T cells in jejunal biopsies. To determine whether subjects with persistent serological markers 4 and 13 years after a population screening survey have the HLA constitution of coeliac disease and/or minor morphometric abnormalities of the small intestine, including raised gamma/delta T-cell counts, as possible indicators of latent coeliac disease. SUBJECTS: Participants with positive serology detected by the Belfast MONICA Project surveys (1983 and 1991) were subdivided into those with persistently positive serology (persistent serology), negative serology at follow-up (transient serology) and those with enteropathy (coeliac disease). Morphometric features were compared with MONICA controls who had negative serology and HLA antigen frequencies were compared with blood donor controls. METHODS: Subjects were followed up in 1994-1996 and were re-tested for IgA antibodies to gliadin, endomysium and reticulin. HLA typing was carried out and IELs and gamma/delta T-cell counts were assessed in jejunal biopsies in subjects who gave consent. RESULTS: Persistent serology mainly concerned antigliadin (AGA) and antireticulin (ARA) antibodies but one patient had positive antiendomysial antibody (EMA) and ARA in 1983, which became negative at follow-up, at which time they were positive for AGA. No significant differences were observed between IELs or gamma/delta T-cell counts when the persistent and transient groups were compared in turn with the MONICA controls. HLA-DR2 was expressed in 11 of 16 in the persistent group compared to 47 of 150 blood donor controls (P = 0.013). HLA-DR3 occurred in 15 of 17 coeliac patients compared to 37 of 150 blood donors (P = 0.00001). CONCLUSIONS: Persistent serological markers following population screening do not appear to indicate latent coeliac disease.
Adult↗
A prospective randomised trial of a "test and treat" policy versus endoscopy based management in young Helicobacter pylori positive patients with ulcer-like dyspepsia, referred to a hospital clinic.
BACKGROUND: Management of dyspepsia remains a controversial area. Although the European Helicobacter pylori study group has advised empirical eradication therapy without oesophagogastroduodenoscopy (OGD) in young H pylori positive dyspeptic patients who do not exhibit alarm symptoms, this strategy has not been subjected to clinical trial. AIMS: To compare a "test and treat" eradication policy against management by OGD. PATIENTS: Consecutive subjects were prospectively recruited from open access OGD and outpatient referrals. METHODS: H pylori status was assessed using the carbon-13 urea breath test. H pylori positive patients were randomised to either empirical eradication or OGD. Symptoms and quality of life scores were assessed at baseline and subsequent reviews over a 12 month period. RESULTS: A total of 104 H pylori positive patients aged under 45 years were recruited. Fifty two were randomised to receive empirical eradication therapy and 52 to OGD. Results were analysed using an intention to treat policy. Dyspepsia scores significantly improved in both groups over 12 months compared with baseline; however, dyspepsia scores were significantly better in the empirical eradication group. Quality of life showed significant improvements in both groups at 12 months; however, physical role functioning was significantly improved in the empirical eradication group. Fourteen (27%) in the empirical eradication group subsequently proceeded to OGD because of no improvement in dyspepsia. CONCLUSIONS: This randomised study strongly supports the use of empirical H pylori eradication in patients referred to secondary practice; it is estimated that 73% of OGDs in this group would have been avoided with no detriment to clinical outcome.
Adult↗
Dietary intake, smoking, and transient anti-gliadin antibodies.
BACKGROUND: The detection of IgA anti-gliadin antibodies in adults can either be helpful in the diagnosis of coeliac disease, be persistent in subjects with normal jejunal mucosa, or occur transiently. We decided to investigate the effects of smoking, alcohol consumption, and dietary intake on the development of IgA anti-gliadin antibodies. METHODS: Serum samples from subjects enrolled from a large Northern Ireland population sample (MONICA survey) were screened for IgA anti-endomysium and IgA anti-gliadin antibodies. All subjects with positive antibodies were invited for clinical assessment 3-4 years after the initial screening sample. During this follow-up a repeat serum sample was obtained and a jejunal biopsy performed. At enrollment in the MONICA survey, lifestyle information including smoking, alcohol consumption, and dietary intake was obtained. RESULTS: At follow-up 13 subjects had persistent positive serology and villous atrophy, and 9 had persistent positive serology but normal jejunal histology; in 29 the serology had returned to normal, and the jejunal histology was normal There was no difference in smoking, alcohol consumption, or dietary intake between subjects with and without coeliac disease. Subjects with transient serology findings ate significantly more soda bread than the other groups (at the time of initial screening). Analysis of gliadin content of soda bread and plain white bread showed a significantly higher amount of gliadin present in soda bread. CONCLUSIONS: Subjects with transient IgA anti-gliadin antibodies eat significantly more soda bread. The gliadin content of Irish soda bread contained a greater amount of gliadin than white bread. Eating breads with high available gliadin content may cause the appearance of anti-gliadin antibody.
Adult↗
Coeliac disease detected by screening is not silent--simply unrecognized.
Coeliac disease (CD) is associated with a wide spectrum of clinical presentation and may be overlooked as a diagnosis. There is some evidence that untreated CD is associated with a doubling of mortality, largely due to an increase in the incidence of malignancy and small intestinal lymphoma, which is decreased by a strict gluten-free diet. We studied the clinical features of screening-detected coeliacs compared to age- and sex-matched controls as a 3-year follow-up to a population screening survey, and followed-up subjects who had had CD-associated serology 11 years previously to determine whether they have CD or an increased mortality rate compared to the general population. Samples of the general population (MONICA 1991 and 1983) were screened for CD-associated serology and followed-up after 3 and 11 years, respectively, and assessed by a clinical questionnaire, screening blood tests and jejunal biopsy. Mortality rates for 'all deaths' and 'cancer deaths' were compared in subjects with positive serology in 1983 with reference to the general population. Thirteen coeliacs were diagnosed by villous atrophy following screening, compared to two patients with clinically detected CD, giving a prevalence of 1:122. Clinical features or laboratory parameters were not indicative of CD compared to controls. Subjects with positive serology followed up after 11 years did not have an excess mortality for either cancer deaths or all causes of death. Screening-detected CD is rarely silent and may be associated with significant symptoms and morbidity. In this limited study with small numbers, there does not appear to be an increased mortality from screening-detected CD, although the follow-up may be too short to detect any difference.
Adult↗
Serological markers for coeliac disease: changes with time and relationship to enteropathy.
UNLABELLED: Antigliadin antibodies (AGA) may be present in healthy adults. One previous study has reported that IgA-AGA detected by population screening may become negative after a 6-year follow-up period. OBJECTIVES: To determine the variability of coeliac disease-associated antibodies with time and to ascertain which antibodies are predictive of the presence of enteropathy. DESIGN: A clinical follow-up study of subjects with positive serological markers detected by screening at the time of the Belfast MONICA Project. METHODS: Jejunal biopsies were carried out endoscopically by means of a Crosby capsule. IgA-antigliadin was detected by a commercial ELISA; IgA-antiendomysial and antireticulin antibodies were determined by indirect immunofluorescence. RESULTS: Of 48 subjects followed up after 4 years, 28 (58%) had developed negative serology and 20 (42%) had persistently positive serology. Thirteen of 20 subjects with persistent serology had villous atrophy. Of 68 subjects followed up after 13 years, 32 (47%) had developed negative serology and 36 (53%) had persistent serology. Of 10 subjects with persistent serology who were biopsied, four had villous atrophy. None of the subjects who developed negative serology were found to have coeliac disease. CONCLUSIONS: Persistence of serological markers as a follow-up to a population screening programme may predict enteropathy in some subjects, whereas subjects who develop negative serology may be reassured. Subjects with persistent serology and normal histology require follow-up to determine if these markers are indicative of latent coeliac disease.
Biomarkers↗
The effect of treating reflux oesophagitis with omeprazole on quality of life.
BACKGROUND/AIMS: Despite the commonplace nature of heartburn and reflux oesophagitis, little is known of their impact on patients' quality of life. The aim of this study was to assess quality of life in oesophagitis patients before and after medical therapy and compare the results with a sample of the general population. METHODS: Consecutive attenders with frequent heartburn and grade II-III oesophagitis on endoscopy were recruited from one of two centres and treated with omeprazole 20 mg BD for 8-14 weeks. A symptomatic questionnaire, including the Short Form-36 (SF-36) quality of life questionnaire, was completed before and at the end of treatment. Actual quality of life scores were compared with 'expected' scores derived from a sample (n = 3015) of the Northern Ireland population. RESULTS: Seventy two (83%) of the 87 patients recruited were healed after 14 weeks therapy and 77 completed the SF-36 before and after therapy. Three quality of life parameters (bodily pain, vitality and social function) were significantly lower before treatment than the 'expected' scores. Seven of the quality of life parameters measured by the SF-36 showed a significant improvement after treatment and the eighth (mental health) just failed to achieve a significant improvement (P = 0.06). Comparison of the improvements in SF-36 scores for those who were healed with scores for those who were not healed showed no significant difference. CONCLUSIONS: Patients with grade II-III oesophagitis and frequent heartburn have lower quality of life scores for some parameters than would be expected in the general population. Treatment of the oesophagitis with omeprazole 20 mg BD causes a significant improvement not just in reflux symptoms but in several physical and mental aspects of quality of life regardless of whether or not the oesophagitis is healed.
Adult↗
Prevalence of coeliac disease in Northern Ireland.
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Adult↗
Maintenance therapy with cisapride after healing of erosive oesophagitis: a double-blind placebo-controlled trial.
BACKGROUND: There are few data on the role of prokinetic agents as maintenance therapy in moderately severe reflux oesophagitis despite the high relapse rate of this condition after healing. AIMS: To determine whether cisapride is more effective than placebo as maintenance therapy after healing of moderate erosive oesophagitis in two respects: first, in preventing symptomatic relapse and preserving quality of life; and, second, in improving oesophageal motor function. PATIENTS: Forty-two patients whose grade II-III oesophagitis had been healed with omeprazole were randomized to receive either cisapride 20 mg nocte or placebo for 6 months. Oesophageal pH monitoring and manometry were performed before starting maintenance therapy and after 4 weeks, and symptomatic status and quality of life were assessed at weeks 0, 4, 13 and 26. RESULTS: After 4 weeks of maintenance therapy, lower oesophageal sphincter pressure improved in the cisapride group (16.4-21.9 mmHg, P = 0.01) but not in the placebo group (25.5-22.7 mmHg, P = 0.2). Oesophageal pH monitoring showed no significant changes in either group. Sixteen (76%) cisapride patients and 12 (57%) placebo patients withdrew within 4 weeks owing to symptomatic relapse (P = 0.2). After 26 weeks, 21 (100%) cisapride and 17 (81%) placebo patients had relapsed (log-rank analysis of survival time P = 0.07). Quality of life parameters deteriorated in both treatment groups to a similar degree. CONCLUSION: Maintenance therapy with cisapride 20 mg nocte improves the lower oesophageal sphincter pressure in patients whose oesophagitis has been healed with omeprazole. However, cisapride is no better than placebo in preventing symptomatic relapse or deterioration in quality of life.
Adult↗
The breath test--a call for more regional use.
OBJECTIVE: Although the 13C-urea breath test is commonly used for detection of Helicobacter pylori infection and eradication, access to commercial testing centres for analysis may at times limit its use. We have addressed this issue by establishing a regional-based means of analysis as a Hospital-University collaboration. DESIGN/METHODS: A blind comparison was undertaken of 13C-urea breath test results performed 'in house' by the stable isotope laboratory in Queen's University Belfast and a commercially available 13C-urea breath test. RESULTS: The H. pylori status of the patients (n = 110) agreed for all patients (kappa score = 1). The excess values showed good agreement. The cost of the 'in house' breath test was less than 20 pounds compared with 32.90 pounds for the commercial breath test. CONCLUSION: Regional access to the 13C-urea breath test could decrease costs, increase availability of testing, improve local health services and economy and increase collaborative research opportunities.
Breath Tests↗
Double blind cross-over placebo controlled study of omeprazole in the treatment of patients with reflux symptoms and physiological levels of acid reflux--the "sensitive oesophagus".
BACKGROUND: At least 10-15% of patients with reflux symptoms have a normal endoscopy and physiological levels of acid reflux on pH monitoring. Such patients with 50% or more of symptoms associated with acid reflux episodes have "a positive symptom index" (SI), and it has been proposed that this defines the "sensitive oesophagus". AIM: To test the response to omeprazole 20 mg twice daily for four weeks of patients with normal levels of acid reflux using a randomised, placebo controlled, double blind, cross-over design. PATIENTS: Eighteen patients with normal levels of reflux, 12 of whom had a positive SI. METHODS: Response was measured by symptomatic assessment and the SF-36 quality of life (QOL) questionnaire. RESULTS: Patients with a positive SI showed the following improvements on omeprazole compared with placebo: decrease in symptom frequency (p < 0.01), severity (p < 0.01) and consumption of antacids (p < 0.01). In the group with a negative SI only one patient clearly improved. The QOL parameters for bodily pain (65.6 v 53.4, p = 0.03) and vitality (60.6 v 48.8, p = 0.049) were significantly better on omeprazole than placebo for the group overall. CONCLUSION: Omeprazole improves symptoms in 11 of 18 patients with normal endoscopy and pH monitoring, particularly those with a positive SI. This supports the theory that such patients have an oesophagus which is "sensitive" to acid reflux and are part of the GORD spectrum.
Adult↗
Pre-operative neutrophil and monocyte activation state predicts post-operative neutrophil and monocyte function.
OBJECTIVE: To find out if the in vitro responses of neutrophils (PMN) and monocytes preoperatively can predict their activation postoperatively. DESIGN: Prospective open study. SETTING: Teaching hospital, Ireland. SUBJECTS: 46 Patients (32 men, 14 women, mean age 65 years, range 33-85) who were to undergo elective major vascular or gastrointestinal operations for benign (n = 18) or malignant (n = 28) diseases. INTERVENTIONS: Measurement by flow cytometry of functional (PMN and monocyte respiratory burst activity) and phenotypic (expression of PMN CD 11b adhesion receptors and monocyte CD14 receptors) markers of activation. MAIN OUTCOME MEASURES: Correlation between mean channel fluorescence (MCF) preoperatively and postoperatively. RESULTS: In 24 patients PMN respiratory burst activity was increased before operation and had decreased significantly (p < 0.01) on postoperative day 1 (high responders group). In the remaining 22 patients (low responders group) respiratory burst activity was low before operation and had increased significantly (p < 0.05) on postoperative day 1. PMN CD 11b activity followed a similar trend. Monocyte activity responded similarly (in the high group mean (SEM) MCF preoperatively was 69.14 (13.15) compared with 58.23 (10.8) on day 1, and in the low group the corresponding figures were 38.5 (7.01) and 8.43 (5.2). Expression of CD14 did not differ between the groups and was less postoperatively than preoperatively. The groups did not differ in age, sex, APACHE 11 scores, smoking habits or types of disease and there was no major infective complications in either group. CONCLUSION: There are two distinct patterns of PMN and monocyte responses to injury that are independant of age, sex and severity of operation. These may be associated with the degree of stress preoperatively or with genetic factors.
Adult↗
Diagnosis of common bile duct stones by intravenous cholangiography: prediction by ultrasound and liver function tests compared with endoscopic retrograde cholangiography.
BACKGROUND: Routine intravenous cholangiography using the safer contrast medium, meglumine iotroxate, may be a useful investigation prior to laparoscopic cholecystectomy for the detection of suspected common bile duct stones. We compared this with endoscopic cholangiography. METHODS: Eighty-one consecutive nonjaundiced patients (mean age 62 years; range 20 to 90) with suspected common bile duct stones referred for endoscopic cholangiography to one center underwent intravenous cholangiography that was considered positive if it detected ductal stones. The ability of ultrasound scans and liver function tests to predict ductal stones was also assessed. RESULTS: Sixty patients had both endoscopic and intravenous cholangiograms performed. Thirteen out of 27 patients with ductal stones confirmed by endoscopic cholangiography had positive intravenous cholangiograms, and 29 out of 30 with no stones had negative intravenous cholangiograms. The sensitivity for intravenous cholangiography was 48%, specificity 97%, positive predictive value 93%, negative predictive value 67%, and accuracy 73%. For ultrasound scans the positive predictive value was 69%; negative predictive value was 78%. For liver function tests the positive predictive value was 68%; negative predictive value was 93%. CONCLUSIONS: Intravenous cholangiography cannot be recommended instead of endoscopic cholangiography except in situations where the latter is not readily available. Ultrasound and liver function tests are useful in predicting ductal stones.
Adult↗