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Showing papers in "Gut in 1996"


Journal ArticleDOI
01 Mar 1996-Gut
TL;DR: It was found that age, shock, comorbidity, diagnosis, major stigmata of recent haemorrhage, and rebleeding are all independent predictors of mortality when assessed using multiple logistic regression and a numerical score that closely follows the predictions generated by logistical regression equations was developed.
Abstract: The aim of this study was to establish the relative importance of risk factors for mortality after acute upper gastrointestinal haemorrhage, and to formulate a simple numerical scoring system that categorizes patients by risk. A prospective, unselected, multicentre, population based study was undertaken using standardised questionnaires in two phases one year apart. A total of 4185 cases of acute upper gastrointestinal haemorrhage over the age of 16 identified over a four month period in 1993 and 1625 cases identified subsequently over a three month period in 1994 were included in the study. It was found that age, shock, comorbidity, diagnosis, major stigmata of recent haemorrhage, and rebleeding are all independent predictors of mortality when assessed using multiple logistic regression. A numerical score using these parameters has been developed that closely follows the predictions generated by logistical regression equations. Haemoglobin, sex, presentation (other than shock), and drug therapy (non-steroidal anti-inflammatory drugs and anticoagulants) are not represented in the final model. When tested for general applicability in a second population, the scoring system was found to reproducibly predict mortality in each risk category. In conclusion, a simple numerical score can be used to categorize patients presenting with acute upper gastrointestinal haemorrhage by risk of death. This score can be used to determine case mix when comparing outcomes in audit and research and to calculate risk standardised mortality. In addition, this risk score can identify 15% of all cases with acute upper gastrointestinal haemorrhage at the time of presentation and 26% of cases after endoscopy who are at low risk of rebleeding and negligible risk of death and who might therefore be considered for early discharge or outpatient treatment with consequent resource savings.

1,265 citations


Journal ArticleDOI
01 Nov 1996-Gut
TL;DR: The higher overall incidence rates in northern centres did not seem to be explained by differences in tobacco consumption or education, and the magnitude of the observed excess for both conditions is less than expected on the basis of previous studies.
Abstract: BACKGROUND: It has been suggested that the incidence of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is three or more times higher in northern than in southern Europe. The aim of this EC funded study was to investigate this apparent variation by ascertaining the incidence of IBD across Europe. METHODS: For the period 1 October 1991 to 30 September 1993 all new patients diagnosed with IBD were prospectively identified in 20 European centres according to a standard protocol for case ascertainment and definition. FINDINGS: Altogether 2201 patients aged 15 years or more were identified, of whom 1379 were diagnosed as UC (including proctitis), 706 as CD, and 116 as indeterminate. The overall incidence per 100,000 at ages 15-64 years (standardised for age and sex) of UC was 10.4 (95% confidence interval (95% CI) 7.6 to 13.1) and that of CD was 5.6 (95% CI 2.8 to 8.3). Rates of UC in northern centres were 40% higher than those in the south (rate ratio (RR) = 1.4 (95% CI 1.2 to 1.5)) and for CD they were 80% higher (RR = 1.8 (95% CI 1.5 to 2.1)). For UC the highest reported incidence was in Iceland (24.5, 95% CI 17.4 to 31.5) and for CD, Maastricht (The Netherlands; 9.2, 95% CI 6.5 to 11.8) and Amiens (north west France; 9.2, 95% CI 6.3 to 12.2). The lowest incidence of UC was in Almada (southern Portugal) (1.6, 95% CI 0.0 to 3.2) and of CD in Ioannina (north west Greece) (0.9, 95% CI 0.0 to 2.2). An unexpected finding was a difference in the age specific incidence of UC in men and women with the incidence in women but not men declining with age. INTERPRETATION: The higher overall incidence rates in northern centres did not seem to be explained by differences in tobacco consumption or education. Nevertheless, the magnitude of the observed excess for both conditions is less than expected on the basis of previous studies. This may reflect recent increases in the incidence of IBD in southern Europe whereas those in the north may have stabilised.

1,035 citations


Journal ArticleDOI
01 Apr 1996-Gut
TL;DR: It was found that age, serum bilirubin concentration, and histological stage at the time of diagnosis were independent predictors of a bad prognosis, which should be of value for the timing of transplantation and patient counselling in PSC.
Abstract: BACKGROUND/AIMS--The course of primary sclerosing cholangitis (PSC) is highly variable and unpredictable. This study describes the natural history and outcome of PSC. These data were used to construct a prognostic model for patients with PSC. METHODS--A total of 305 Swedish patients with PSC were studied. The median follow up time was 63 (1-194) months and all patients could be traced for follow up. Some 79 patients died or had a liver transplant. The prognostic significance of clinical, biochemical, and histological findings at the time of diagnosis were evaluated using multivariate analysis. RESULTS--The estimated median survival from time of diagnosis to death or liver transplantation was 12 years. Cholangiocarcinoma was found in 24 (8%) of the patients and 134 (44%) of the patients were asymptomatic at the time of diagnosis. The estimated survival rate was significantly higher in the asymptomatic group (p < 0.001). However, 29 (22%) of the asymptomatic patients became symptomatic during the study period. It was found that age, serum bilirubin concentration, and histological stage at the time of diagnosis were independent predictors of a bad prognosis. These variables were used to construct a prognostic model. CONCLUSIONS--This prognostic model developed from a large homogeneous population of PSC patients should be of value for the timing of transplantation and patient counselling in PSC.

751 citations


Journal ArticleDOI
01 Jun 1996-Gut
TL;DR: If the early pattern of change in inflammatory markers or other variables could predict the need for surgery and the outcome of medical treatment during one year follow up is evaluated, patients with frequent stools, or raised CRP, need to be identified, as most will require colectomy on that admission.
Abstract: BACKGROUND: Simple criteria are needed to predict which patients with severe ulcerative colitis will respond poorly to intensive medical treatment and require colectomy. AIMS: To find out if the early pattern of change in inflammatory markers or other variables could predict the need for surgery and to evaluate the outcome of medical treatment during one year follow up. PATIENTS: 51 consecutive episodes of severe colitis (Truelove and Witts criteria) affecting 49 patients admitted to John Radcliffe Hospital, Oxford. METHODS: Prospective study monitoring 36 clinical, laboratory, and radiographic variables. All episodes treated with intravenous and rectal hydrocortisone and 14 of 51 with cyclosporine. RESULTS: Complete response in 21 episodes ( 3 stools or visible blood on day 7, but no colectomy), and colectomy on that admission in 15. During the first five days, stool frequency and C reactive protein (CRP) distinguished between outcomes (p 45 mg/l, would require colectomy. For patients given cyclosporine, four of 14 avoided colectomy but two continued to have symptoms. After admission, complete responders remained in remission for a median nine months and had a 5% chance of colectomy. Incomplete responders had a 60% chance of continuous symptoms and 40% chance of colectomy. CONCLUSIONS: After three days intensive treatment, patients with frequent stools (> 8/day), or raised CRP (> 45 mg/l) need to be identified, as most will require colectomy on that admission. The role of cyclosporine for treating severe colitis has yet to be defined. After seven days' treatment, patients with > 3 stools/day of visible blood have a 60% chance of continuous symptoms and 40% chance of colectomy in the following months.

637 citations


Journal ArticleDOI
01 Feb 1996-Gut
TL;DR: The strong correlation between PSC and pouchitis suggest a common link in their pathogenesis and may be associated with pouchitis after ileal pouch-anal anastomosis.
Abstract: Primary sclerosing cholangitis (PSC), present in 5% of patients with ulcerative colitis, may be associated with pouchitis after ileal pouch-anal anastomosis. The cumulative frequency of pouchitis in patients with and without PSC who underwent ileal pouch-anal anastomosis for ulcerative colitis was determined. A total of 1097 patients who had an ileal pouch-anal anastomosis for ulcerative colitis, 54 with associated PSC, were studied. Pouchitis was defined by clinical criteria in all patients and by clinical, endoscopic, and histological criteria in 83% of PSC patients and 85% of their matched controls. PSC was defined by clinical, radiological, and pathological findings. One or more episodes of pouchitis occurred in 32% of patients without PSC and 63% of patients with PSC. The cumulative risk of pouchitis at one, two, five, and 10 years after ileal pouch-anal anastomosis was 15.5%, 22.5%, 36%, and 45.5% for the patients without PSC and 22%, 43%, 61%, and 79% for the patients with PSC. In the PSC group, the risk of pouchitis was not related to the severity of liver disease. In conclusion, the strong correlation between PSC and pouchitis suggest a common link in their pathogenesis.

499 citations


Journal ArticleDOI
01 Oct 1996-Gut
TL;DR: Faecal elastase 1 determination proved to be a highly sensitive and specific tubeless pancreatic function test and accordingly categorised according to the secretin-caerulein test as "gold standard".
Abstract: BACKGROUND: Indirect pancreatic function tests available today are unreliable for clinical practice in early chronic pancreatitis due to their low sensitivity in mild and moderate exocrine pancreatic insufficiency. AIM: To evaluate the sensitivity, specificity, and practicability of faecal elastase 1 determination in patients with mild, moderate, and severe exocrine pancreatic insufficiency categorised according to the secretin-caerulein test as "gold standard'. PATIENTS AND METHODS: Faecal and duodenal elastase 1 concentration (commercial enzyme linked immunosorbent assay (ELISA)), faecal chymotrypsin activity, faecal fat analysis, and the secretin-caerulein test were performed on 44 patients with mild (n = 8), moderate (n = 14), and severe (n = 22) exocrine pancreatic insufficiency and 35 patients with gastrointestinal diseases of non-pancreatic origin. Fifty healthy volunteers were studied as normal controls. Morphological examinations were carried out to definitely confirm or exclude chronic pancreatitis. RESULTS: With a cut off of 200 micrograms elastase 1/g stool the sensitivity was 63% for mild, 100% for moderate, 100% for severe, and 93% for all patients with exocrine pancreatic insufficiency, and specificity was 93%. Values for chymotrypsin were 64% (sensitivity) and 89% (specificity). Significant (p < 0.001) correlations were found for faecal and duodenal elastase with duodenal lipase, amylase, trypsin, volume, and bicarbonate output. Individual day to day variations of faecal elastase 1 concentrations were very low (mean CV = 15%) and sample storage at room temperature is possible for at least one week. CONCLUSIONS: Faecal elastase 1 determination proved to be a highly sensitive and specific tubeless pancreatic function test.

490 citations


Journal ArticleDOI
01 Apr 1996-Gut
TL;DR: It is suggested that increased apoptosis may be the stimulus for a compensatory hyperproliferative and potentially preneoplastic response in chronic H pylori infection.
Abstract: BACKGROUND--Helicobacter pylori may promote gastric carcinogenesis through increasing gastric epithelial cell proliferation. How H pylori does so is unknown. Programmed, non-necrotic, cell death (apoptosis) occurs throughout the gut and is linked to proliferation. It was hypothesised that H pylori may induce hyper-proliferation through increasing apoptosis. AIM--To measure the effect of H pylori infection on gastric epithelial apoptosis in situ. PATIENTS--Patients with duodenal ulcers treated to eradicate H pylori and patients with H pylori negative non-ulcer dyspepsia. METHODS--Retrospective quantification of apoptotic epithelial cells in situ from formalin fixed biopsy specimens, counted after staining by terminal uridine deoxynucleotidyl nick end-labelling. RESULTS--In the uninfected stomach, apoptotic cells were rare and situated in the most superficial portion of gastric glands (mean 2.9% of epithelial cells). In H pylori infection, they were more numerous and were located throughout the depth of gastric glands, comprising 16.8% of epithelial cells, falling to 3.1% after H pylori eradication, p = 0.017. Apoptotic cell number did not correlate with the degree of histological gastritis. CONCLUSIONS--These results suggest that H pylori induces epithelial apoptosis in vivo. Increased apoptosis may be the stimulus for a compensatory hyperproliferative and potentially preneoplastic response in chronic H pylori infection.

417 citations


Journal ArticleDOI
01 Mar 1996-Gut
TL;DR: In contrast with normal subjects where IgA is the main immunoglobulin in the intestine, patients with active inflammatory bowel disease (IBD) produce high concentrations of IgG from intestinal lymphocytes, but the antigens at which these antibodies are directed are unknown.
Abstract: In contrast with normal subjects where IgA is the main immunoglobulin in the intestine, patients with active inflammatory bowel disease (IBD) produce high concentrations of IgG from intestinal lymphocytes, but the antigens at which these antibodies are directed are unknown. To investigate the specificities of these antibodies mucosal immunoglobulins were isolated from washings taken at endoscopy from 21 control patients with irritable bowel syndrome, 10 control patients with intestinal inflammation due to infection or ischaemia, and 51 patients with IBD: 24 Crohn's disease (CD, 15 active, nine quiescent), 27 ulcerative colitis (UC, 20 active, seven inactive). Total mucosal IgG was much higher (p < 0.001) in active UC (median 512 micrograms/ml) and active CD (256 micrograms/ml) than in irritable bowel syndrome controls (1.43 micrograms/ml), but not significantly different from controls with non-IBD intestinal inflammation (224 micrograms/ml). Mucosal IgG bound to proteins of a range of non-pathogenic commensal faecal bacteria in active CD; this was higher than in UC (p < 0.01); and both were significantly greater than controls with non-IBD intestinal inflammation (CD p < 0.001, UC p < 0.01) or IBS (p < 0.001 CD and UC). This mucosal IgG binding was shown on western blots and by enzyme linked immunosorbent assay (ELISA) to be principally directed against the bacterial cytoplasmic rather than the membrane proteins. Total mucosal IgA concentrations did not differ between IBD and controls, but the IgA titres against faecal bacteria were lower in UC than controls (p < 0.01). These experiments show that there is an exaggerated mucosal immune response particularly in active CD but also in UC directed against cytoplasmic proteins of bacteria within the intestinal lumen; this implies that in relapse of IBD there is a breakdown of tolerance to the normal commensal flora of the gut.

410 citations


Journal ArticleDOI
01 Mar 1996-Gut
TL;DR: NGAL synthesis is induced in epithelial cells in inflammatory and neoplastic, colorectal diseases and may serve an important anti-inflammatory function as a scavenger of bacterial products.
Abstract: In inflammatory and neoplastic disorders of the colon a defect barrier function of the mucosa may result in absorption of bacterial products from the intestinal lumen. These products may further recruit inflammatory cells and thus augment the inflammatory response. A novel lipocalin in neutrophils, neutrophil gelatinase associated lipocalin (NGAL), with the ability to bind bacterial formylpeptides, has been described and therefore it is of interest to investigate the expression of this protein in diseases of the colon. Expression of NGAL was investigated by immunohistochemistry and by mRNA in situ hybridisation in normal colon and in neoplastic and inflammatory colorectal diseases. A very high expression of NGAL was seen in colonic epithelium in areas of inflammation, both in non-malignant epithelium (diverticulitis, inflammatory bowel disease, and appendicitis) as well as in premalignant and malignant neoplastic lesions of the colon. In adenocarcinoma, the NGAL expression was especially abundant in the transitional mucosa and in the superficial ulcerated area. On the other hand, no NGAL expression could be detected in lymph node metastases from these adenocarcinomas. A weak expression of NGAL in some epithelial cells was only occasionally seen in normal colon. In conclusion, NGAL synthesis is induced in epithelial cells in inflammatory and neoplastic, colorectal diseases. NGAL may serve an important anti-inflammatory function as a scavenger of bacterial products.

395 citations


Journal ArticleDOI
L R Ranganath1, J M Beety, L M Morgan, J W Wright, R Howland, V Marks 
01 Jun 1996-Gut
TL;DR: Postprandial GLP-1 secretion in response to oral carbohydrate is considerably attenuated in obese subjects and it is suggested that both this fall and the overall reduction in GLp-1 values in obese Subjects may be related to an increase in plasma non-esterified fatty acids.
Abstract: BACKGROUND: Hypersecretion of insulinotropic factors such as glucose dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1(7-36)amide (GLP-1) have been postulated to account for the hyperinsulinaemia of obesity. AIMS: To examine the role of GLP-1 and GIP in obese women and matched controls. SUBJECTS: Six lean and six obese women subjects matched for age. METHODS: The gut hormone, plasma glucose, and serum triglyceride responses were studied over 180 minutes after oral carbohydrate and fat meals. Heparin (10,000 units) was given intravenously at 120 minutes. RESULTS: There was pronounced attenuation of plasma GLP-1 secretion to oral carbohydrate in the obese compared with lean subjects but no such difference in response to oral fat load. There were no differences in the plasma GIP responses to carbohydrate or fat feeding. There was an apparent fall in plasma GLP-1 values in all subjects after administration of heparin. CONCLUSION: Postprandial GLP-1 secretion in response to oral carbohydrate is considerably attenuated in obese subjects. The cause of this attenuation of GLP-1 secretion is not known although we suggest that both this fall and the overall reduction in GLP-1 values in obese subjects may be related to an increase in plasma non-esterified fatty acids.

367 citations


Journal ArticleDOI
01 Dec 1996-Gut
TL;DR: In this article, a plan for the treatment of a newly diagnosed patient with collagenous colitis is proposed, where Prednisolone was most effective with a response rate of 82%, but the required dose was often high and the effect was not sustained after withdrawal.
Abstract: BACKGROUND: Data on collagenous colitis have been based on a limited number of patients. AIMS: To obtain more information on this disease from a register set up at Orebro Medical Center Hospital. PATIENTS AND METHODS: Twenty five Swedish hospitals have contributed to this patient register, which comprises 163 histopathologically verified cases. Clinical data were retrospectively analysed. RESULTS: Collagenous colitis followed a chronic intermittent course in most cases (85%) with a sudden onset in 42%. Symptoms were chronic watery diarrhoea, often nocturnal (27%), abdominal pain (41%), and weight loss (42%). Sixty six patients (40%) had one or more associated diseases. Routine laboratory data were mostly normal. The median age at diagnosis was 55 (range 16-86) years, but 25% of the patients were younger than 45 years. Seven patients died of unrelated diseases. The response rate for sulphasalazine was 59%, and 50% and 40% for mesalazine and olsalazine. Prednisolone was most effective with a response rate of 82%, but the required dose was often high and the effect was not sustained after withdrawal. Antibiotics were efficient in 63%. Cholestyramine and loperamide had response rates of 59% and 71% respectively. CONCLUSIONS: Collagenous colitis follows a chronic continuous course. Symptoms can be socially disabling, but the disease does not seem to have a malignant potential. A plan for the treatment of a newly diagnosed patient with collagenous colitis is proposed.

Journal ArticleDOI
01 Jul 1996-Gut
TL;DR: The results show that the incidence of gastric and duodenal bacterial overgrowth is considerably higher in patients treated with omeprazole compared with cimetidine, which can be explained by more pronounced inhibition of Gastric acid secretion.
Abstract: BACKGROUND: Gastric and duodenal bacterial overgrowth frequently occurs in conditions where diminished acid secretion is present. Omeprazole inhibits acid secretion more effectively than cimetidine and might therefore more frequently cause bacterial overgrowth. AIM: This controlled prospective study compared the incidence of gastric and duodenal bacterial overgrowth in patients treated with omeprazole or cimetidine. METHODS: 47 outpatients with peptic disease were randomly assigned to a four week treatment regimen with omeprazole 20 mg or cimetidine 800 mg daily. Gastric and duodenal juice were obtained during upper gastrointestinal endoscopy and plated for anaerobic and aerobic organisms. RESULTS: Bacterial overgrowth (> or = 10(5) cfu/ml) was present in 53% of the patients receiving omeprazole and in 17% receiving cimetidine (p < 0.05). The mean (SEM) number of gastric and duodenal bacterial counts was 6.0 (0.2) and 5.0 (0.2) respectively in the omeprazole group and 4.0 (0.2) and 4.0 (0.1) in the cimetidine group (p < 0.001 and < 0.01; respectively). Faecal type bacteria were found in 30% of the patients with bacterial overgrowth. Basal gastric pH was higher in patients treated with omeprazole compared with cimetidine (4.2 (0.5) versus 2.0 (0.2); p < 0.001) and in patients with bacterial overgrowth compared with those without bacterial overgrowth (5.1 (0.6) versus 2.0 (0.1); p < 0.0001). The nitrate, nitrite, and nitrosamine values in gastric juice did not increase after treatment with either cimetidine or omeprazole. Serum concentrations of vitamin B12, beta carotene, and albumin were similar before and after treatment with both drugs. CONCLUSIONS: These results show that the incidence of gastric and duodenal bacterial overgrowth is considerably higher in patients treated with omeprazole compared with cimetidine. This can be explained by more pronounced inhibition of gastric acid secretion. No patient developed signs of malabsorption or an increase of N-nitroso compounds. The clinical significance of these findings needs to be assessed in studies with long-term treatment with omeprazole, in particular in patients belonging to high risk groups such as HIV infected and intensive care units patients.

Journal ArticleDOI
01 Mar 1996-Gut
TL;DR: In this article, the effects of octreotide treatment on metastatic endocrine gastroenteropancreatic tumours (GEP) were investigated in a prospective German Sandostatin multicentre phase II trial.
Abstract: Antiproliferative treatment of patients with metastatic endocrine gastroenteropancreatic tumours (GEP) is based mainly on chemotherapeutic protocols whereby drug toxicity is a major handicap. Octreotide is the first choice in the control of hormone mediated symptoms. From retrospective and a few prospective studies it has been suggested that octreotide exhibits antiproliferative properties. The prospective German Sandostatin multicentre phase II trial investigated the effects of 200 micrograms octreotide thrice daily for one year on tumour growth and endocrine abnormalities in 103 patients. Octreotide treatment was continued in those patients responding to the drug until tumour progression occurred. In 28 of those with tumour progression during 200 micrograms thrice daily octreotide dose was increased to 500 micrograms thrice daily. The study sample consisted of 52 patients with computed tomography confirmed tumour progression and 13 patients with stable disease before octreotide treatment, whereas no preobservation period was available in 38 patients. Nineteen patients (36.5%) with computed tomography confirmed tumour progression experienced stabilisation of tumour growth lasting for at least three months. Median duration of stable disease was 18 months. At month 12, stable disease continued in 12 patients, declined after 24 months to nine patients, and after 36 months to five patients. Tumour regression has not been seen in this or other subgroups. In the subgroup with stable disease before octreotide, stable disease continued in 53.8% of patients over 12 months. Increase of octreotide dose to 500 micrograms thrice daily did not influence progression seen during the lower dose with the exception of one patient in whom tumour progression changed to stable disease. No association of tumour size response and patients' characteristics could be detected. The results suggest that octreotide inhibits tumour growth in patients with metastasised endocrine GEP tumours. The antiproliferative effect is, at least in some patients, longlasting. Currently, octreotide can only be recommended as an antiproliferative drug if patients with clearly progressive disease show stabilisation after treatment for three to six months.

Journal ArticleDOI
01 Sep 1996-Gut
TL;DR: In this article, 6-Mercaptopurine (6-MP) has confirmed short and longterm efficacy in the treatment of IBD, but the relation between its metabolism, efficacy, and side effects is not well understood.
Abstract: BACKGROUND: 6-Mercaptopurine (6-MP) has confirmed short and longterm efficacy in the treatment of IBD. However, the relation between its metabolism, efficacy, and side effects is not well understood. AIMS: To assay 6-MP metabolites and to correlate levels with drug compliance, disease activity, and adverse effects of treatment. PATIENTS: Heparinised blood was obtained prior to daily administration of 6-MP in 25 adolescent Crohn's disease patients (14 ileocolitis, 11 colitis) receiving 1.2 (range 0.4-1.6) mg/kg/day for a mean of 17 (range 4-65) months. METHODS: Erythrocyte free bases 6-thioguanine (6-TG) and 6-methyl-mercaptopurine (6-MMP) were measured (pmol/8 x 10(8) red blood cells) using reverse phase high performance liquid chromatography. RESULTS: Disease activity (modified Harvey-Bradshaw index) improved significantly with 6-MP (p = 0.001). Clinical remission was achieved in 72% of patients, who stopped taking prednisone, or were successfully weaned to a low alternate day dose (< 0.4 mg/kg/OD). Remission correlated well with erythrocyte 6-TG (p < 0.05), but not 6-MMP levels. Neutropenia was associated with 6-MP use (p < 0.005), but did not correlate with erythrocyte 6-MP metabolite levels. One patient refractory to 6-MP had 6-TG, but no measureable 6-MMP production, suggesting deficient thiopurine methyl-transferase activity or poor compliance. 6-MP induced complications (hepatitis, pancreatitis, and marrow suppression) were generally associated with increased 6-MMP levels. CONCLUSIONS: These results suggest that high performance liquid chromatography measurement of erythrocyte 6-MP metabolites may provide a quantitative assessment of patient responsiveness and compliance to treatment. The data support an immunosuppressive role for 6-TG, and potential cytotoxicity of raised 6-MMP levels.

Journal ArticleDOI
01 Jan 1996-Gut
TL;DR: Most type A and B bile duct injuries after laparoscopic cholecystectomy (80%) can be treated endoscopically and in patients with more severe ductal injury (type C and D) reconstructive surgery is eventually required in 70%.
Abstract: From January 1990 to June 1994, 53 patients who sustained bile duct injuries during laparoscopic cholecystectomy were treated at the Amsterdam Academic Medical Centre. There were 16 men and 37 women with a mean age of 47 years. Follow up was established in all patients for a median of 17 months. Four types of ductal injury were identified. Type A (18 patients) had leakage from cystic ducts or peripheral hepatic radicles, type B (11 patients) had major bile duct leakage, type C (nine patients) had an isolated ductal stricture, and type D (15 patients) had complete transection of the bile duct. Endoscopic retrograde cholangiopancreatography (ERCP) established the diagnosis in all type A, B, and C lesions. In type D lesions percutaneous cholangiography was required to delineate the proximal extent of the injury. Initial treatment (until resolution of symptoms and discharge from hospital) comprised endoscopy in 36 patients and surgery in 26 patients. Endoscopic treatment was possible and successful in 16 of 18 of type A lesions, five of seven of type B lesions, and three of nine of type C lesions. Most failures resulted from inability to pass strictures or leaks at the initial endoscopy. During initial treatment additional surgery was required in seven patients. Fourteen patients underwent percutaneous or surgical drainage of bile collections, or both. After endoscopic treatment early complications occurred in three patients, with a fatal outcome in two (not related to the endoscopic therapy). During follow up six patients developed late complications. All 15 patients with complete transection and four patients with major bile duct leakage were initially treated surgically. During initial treatment additional endoscopy was required in two patients. Early complications occurred in eight patients. During follow up seven patients developed stenosis of the anastomosis or bile duct. Reconstructive surgery in the early postoperative phase was associated with more complications than elective reconstructive surgery. Most type A and B bile duct injuries after laparoscopic cholecystectomy (80%) can be treated endoscopically. In patients with more severe ductal injury (type C and D) reconstructive surgery is eventually required in 70%. Multidisciplinary approach to these lesions is advocated and algorithms for treatment are proposed.

Journal ArticleDOI
01 Jul 1996-Gut
TL;DR: Oesophageal cancer is an uncommon cause of death in patients with Barrett's oesophagus and the patients of this cohort would not have benefited from an endoscopic surveillance programme.
Abstract: BACKGROUND: Barrett9s oesophagus carries a 30-fold to 40-fold increased risk of oesophageal cancer. It is unknown whether endoscopic surveillance programmes reduce mortality from oesophageal cancer. METHODS: A cohort study was undertaken of all 166 patients in whom the diagnosis Barrett9s oesophagus had been established between 1973 and 1986. RESULTS: One hundred and fifty five of 166 patients could be traced (93%). During a mean follow up of 9.3 years (amounting to 1440 patient years) eight patients had developed oesophageal cancer at random intervals (one case in 180 patient years). All but one of the tumours were diagnosed at endoscopy for symptoms, three in the stage of carcinoma in situ. Risk factors for the development of oesophageal cancer were extensive Barrett9s oesophagus exceeding 10 cm (p = 0.02) and Barrett9s ulcer at the time of intake (p = 0.009). Seventy six patients were alive; three had undergone surgery for oesophageal cancer and were without recurrence respectively, 12.8 years, 12.1 years, and 7 months postoperatively. Seventy nine patients had died; five of them had developed oesophageal cancer, but in only two cases this had been the cause of death (2.5%). CONCLUSIONS: Oesophageal cancer is an uncommon cause of death in patients with Barrett9s oesophagus. The patients of this cohort would not have benefited from an endoscopic surveillance programme.

Journal ArticleDOI
01 Sep 1996-Gut
TL;DR: The results show that follow up of unresected colorectal polyps up to 9 mm is safe, and the consistency of growth retardation of medium sized polyps suggests extended intervals between the endoscopic follow up examinations, but the increased number of new polyps in the proximal colon indicates total colonoscopy as the examination of choice.
Abstract: BACKGROUND, AIMS, AND PATIENTS: In a prospective follow up and intervention study of colorectal polyps, leaving all polyps less than 10 mm in situ for three years, analysis of redetection rate, growth, and new polyp formation was carried out in 116 patients undergoing annual colonoscopy. The findings in relation to growth and new polyp formation were applied to 58 subjects who received placebo. RESULTS: Redetection rate varied from 75-90% for each year, and was highest in the rectum and sigmoid colon. There was no net change in size of all polyps in the placebo group, however, polyps less than 5 mm showed a tendency to net growth, and polyps 5-9 mm a tendency to net regression in size, both for adenomas and hyperplastic polyps. This pattern was verified by computerised image analysis. Patients between 50 and 60 years showed evidence of adenoma size increase compared with the older patients, and the same was true for those with multiple adenomas (four to five) compared with those with a single adenoma. The new adenomas were significantly smaller and 71% were located in the right side of the colon. Patients with multiple adenomas had more new polyps at all the follow up examinations than patients with a single adenoma. One patient developed an invasive colorectal carcinoma, which may be evolved from a previously overlooked polyp. Two polyps, showing intramucosal carcinoma after follow up for three years, were completely removed, as judged by endoscopy and histological examination. CONCLUSIONS: The results show that follow up of unresected colorectal polyps up to 9 mm is safe. The consistency of growth retardation of medium sized polyps suggests extended intervals between the endoscopic follow up examinations, but the increased number of new polyps in the proximal colon indicates total colonoscopy as the examination of choice. The growth retardation of the medium sized polyps may partly explain the discrepancy between the prevalence of polyps and the incidence of colorectal cancer.

Journal ArticleDOI
01 Aug 1996-Gut
TL;DR: Colonic transit was faster in men than in women, and postlag gastric emptying was also more rapid; other indices of regional transit were not different between the sexes.
Abstract: BACKGROUND AND AIMS: Measurements of gastrointestinal transit are made in clinical and research gastroenterology, yet their intrinsic variability is not well characterised. In particular, an influence of hormones on transit has been proposed as the basis for gastrointestinal symptoms that vary with the menstrual cycle. Our aims were to quantify individual differences in transit during the menstrual cycle in healthy women and to compare these with the intrinsic variability in healthy men. METHODS: On two occasions, whole gut transit was assessed scintigraphically and colonic transit quantified by radio-opaque markers. Thirty two healthy volunteers (12 women, 20 men) were studied, women during the follicular and luteal phases, men twice within a similar four week period. Diets and exercise were standardised prior to and during both studies. RESULTS: Colonic transit was significantly faster in men, and postlag gastric emptying was also more rapid; other indices of regional transit were not different between the sexes. Total colonic transit time was equally well reflected by the scintigraphic and radio-opaque marker methods. Important intraindividual differences were noted in both sexes. The variances in our samples predicted an 80% chance of detecting (with 95% confidence) a mean effect of menstrual hormones on transit that was in the same range as the intrinsic variation in men. CONCLUSIONS: Colonic transit was faster in men than in women. Although group means in the two studies were almost identical, single assessments of transit in subjects sometimes exhibited considerable variability, implying broad biological variations. Given this intrinsic variability, the influence of menstrual hormones on gastrointestinal transit must be small and of doubtful clinical significance.

Journal ArticleDOI
01 Nov 1996-Gut
TL;DR: These consistently raised TNF-alpha, IL-1 beta and IL-6 secretions by normal appearing mucosa from patients with Crohn's disease provide evidence for a sustained immune stimulation in Crohn't disease even in the absence of patent inflammation.
Abstract: BACKGROUND: Increasing evidence points to a important role for inflammatory cytokines for the pathogenesis of Crohn's disease. AIM: To compare the secretion rate of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) by morphologically normal and inflamed intestinal mucosa from patients with Crohn's disease. RESULTS: Organ cultures of intestinal biopsy specimens taken from areas of affected mucosa from patients with Crohn's disease spontaneously produced increased amounts of TNF-alpha, IL-1 beta, and IL-6 compared with controls but also biopsy specimens taken in macroscopically and microscopically unaffected areas in the same patients. Concentrations of IL-1 beta and IL-6 measured in the supernatant fluid of biopsy cultures were positively correlated with the degree of tissue involvement measured by both endoscopic and histological grading. By contrast, TNF-alpha concentrations were not correlated to endoscopic and histological grading. CONCLUSIONS: These consistently raised TNF-alpha, IL-1 beta and IL-6 secretions by normal appearing mucosa from patients with Crohn's disease provide evidence for a sustained immune stimulation in Crohn's disease even in the absence of patent inflammation. The results shed a new light on the role of inflammatory cytokines in the onset of intestinal tissue damage in Crohn's disease and suggest that the range of intestinal lesions in Crohn's disease may be wider than suspected on the basis of regular endoscopic and histological examinations.

Journal ArticleDOI
01 Feb 1996-Gut
TL;DR: Analysis of IL8 in mucosal biopsy specimens of patients with Crohn's disease and ulcerative colitis by enzyme linked immunosorbent assay (ELISA) and by in situ hybridisation found that IL8 mRNA was only detected in inflammatory cells of the interstitium but not in mucosa epithelial cells.
Abstract: To test whether there is a difference in the expression of interleukin 8 (IL8) between Crohn's disease and ulcerative colitis and to determine the main site of its synthesis this study analysed IL8 in mucosal biopsy specimens of patients with Crohn's disease and ulcerative colitis by enzyme linked immunosorbent assay (ELISA) and by in situ hybridisation. IL8 was measured by ELISA in 38 normal control patients, eight inflammatory control patients, 55 Crohn's disease biopsy specimens (26 patients), and 67 ulcerative colitis biopsy specimens (35 patients). IL8 mRNA was determined in samples by in situ hybridisation using a specific IL8 RNA probe. IL8 protein was significantly increased in macroscopically inflamed specimens of Crohn's disease (median 118 pg/specimen, p < 0.0001), ulcerative colitis (median 140 pg/specimen, p < 0.001), and inflammatory controls (median 30 pg/specimen, p = 0.010) compared with normal controls (median 4 pg/specimen). IL8 was also increased in uninflamed specimens of Crohn's disease (median 46 pg/specimen, p < 0.001) but not of ulcerative colitis patients (median 9 pg/specimen, p = 0.3). IL8 protein in the mucosa correlated significantly with macroscopic inflammation in Crohn's disease (r = 0.47, p < 0.001) and in ulcerative colitis (r = 0.60, p < 0.001). IL8 mRNA was detected by in situ hybridisation in 31 of 55 biopsy specimens (56%) of Crohn's disease patients, in 38 of 67 specimens of ulcerative colitis patients (57%), in five of eight inflammatory controls (63%) and in five of 38 normal controls (13%). Mucosal IL8 mRNA expression correlated with mucosal IL8 protein (r = 0.46, p < 0.001). IL8 mRNA was only detected in inflammatory cells of the interstitium but not in mucosal epithelial cells. IL8 is produced mainly in the lamina propria of the colon in inflammatory bowel disease and correlates with mucosal inflammation.

Journal ArticleDOI
01 Sep 1996-Gut
TL;DR: The similarity of the chemiluminescence responses of colonic biopsy specimens from acetic acid induced colitis and ulcerative colitis to a range of conventional antioxidants and standard treatments suggests that this model is a useful method for testing the antioxidant potential of new therapies for inflammatory bowel disease.
Abstract: BACKGROUND: Reactive oxygen species may mediate tissue injury in inflammatory bowel disease. Aminosalicylates have antioxidant activity and the antioxidants, superoxide dismutase and allopurinol, are of reported benefit in inflammatory bowel disease. AIM: To develop a convenient technique for testing the antioxidant potential of standard and novel therapeutic agents for use in inflammatory bowel disease. METHODS: Amplified chemiluminescence was used to measure reactive oxygen species production by colonic biopsy specimens from rats with acetic acid induced colitis and to assess the in vitro effect of conventional antioxidants, standard therapies and proposed novel therapies for inflammatory bowel disease. RESULTS: The model was validated by demonstrating that the profile of effects on chemiluminescence of acetic acid induced colitis biopsy specimens given by conventional antioxidants (sodium azide, catalase, copper-zinc superoxide dismutase, dimethyl sulphoxide, N-acetylcysteine and ascorbate) and standard therapies (5-aminosalicylate and hydrocortisone) resembled that previously reported using biopsy specimens from ulcerative colitis. Human recombinant manganese superoxide dismutase did not alter chemiluminescence. Two novel compounds, LY231617 (10 mM) and amflutizole (20 mM), reduced chemiluminescence by 98% (n = 5, p = 0.009) and 88% (n = 5, p = 0.03), respectively. CONCLUSIONS: The similarity of the chemiluminescence responses of colonic biopsy specimens from acetic acid induced colitis and ulcerative colitis to a range of conventional antioxidants and standard treatments suggests that this model is a useful method for testing the antioxidant potential of new therapies for inflammatory bowel disease. The antioxidant actions of dimethyl sulphoxide, ascorbate, and the novel compounds, amflutizole and LY231617 in this model suggest that these agents merit further assessment in the treatment of inflammatory bowel disease.

Journal ArticleDOI
01 Dec 1996-Gut
TL;DR: Early enteral nutrition given to patients after major abdominal surgery results in an important reduction in infectious complications.
Abstract: BACKGROUND: This study was undertaken to test the hypothesis that early enteral nutrition might reduce the incidence of serious complications after major abdominal surgery. METHODS: In a randomised double blind prospective trial 30 patients received Nutri-drink and 30 patients received placebo through a nasoduodenal feeding tube. On the day of operation the patients were given median 600 ml of either nutrition or placebo, 60 ml per hour. On the first postoperative day the patients received either 1000 ml (median) of nutrition or placebo, on day 2 1200 ml (median) nutrition, 1400 ml placebo, on day 3 1000 ml (median) nutrition, 1150 ml placebo, and on day 4 1000 ml (median) nutrition, 800 ml placebo. All patients were followed up for 30 days by the same investigator. RESULTS: The two groups were similar with regard to nutritional status and type of operation. The rate of postoperative infectious complications was significantly lower in the nutrition group, two of 30 compared with 14 of 30 in the placebo group (p = 0.0009). CONCLUSION: Early enteral nutrition given to patients after major abdominal surgery results in an important reduction in infectious complications.

Journal ArticleDOI
01 Jul 1996-Gut
TL;DR: The cause of ulcerative colitis is unknown but it is likely to depend on an interaction between genetic factors, which may determine the immune response or the expression of enzymes that control intracellular metabolism, and environmental factors, such as diet and the nature of the bacterial flora.
Abstract: The cause of ulcerative colitis (UC) is unknown but it is likely to depend on an interaction between genetic factors, which may determine the immune response or the expression of enzymes that control intracellular metabolism, and environmental factors, such as diet and the nature of the bacterial flora. Ultimately, these factors result in the breakdown in the integrity of the colonic epithelial cell barrier and the perpetuation of inflammation. This review focuses

Journal ArticleDOI
01 Apr 1996-Gut
TL;DR: In this paper, the authors examined whether continuation of enteral nutrition as a nocturnal supplement to an ad libitum daytime intake of a normal diet increased the length of remission of Crohn9s disease in children.
Abstract: BACKGROUND--Liquid diets given enterally combined with "bowel rest9 are efficacious in the treatment of active Crohn9s disease, but rapid recrudescence of gastrointestinal symptoms after resumption of a normal diet is common. AIMS--This study examined whether continuation of enteral nutrition as a nocturnal supplement to an ad libitum daytime intake of a normal diet increased the length of remission of Crohn9s disease in children. PATIENTS AND METHODS--Children and adolescents with active Crohn9s disease treated successfully with exclusive enteral nutrition were classified retrospectively according to whether they continued supplementary enteral nutrition or not. Time to relapse and linear growth were compared between the two cohorts. RESULTS--Between January 1986 and December 1992, 65 patients aged 7-17 years (mean (SD) 13.6 (2.1) years) (36 males, 29 females) with Crohn9s disease in exacerbation were treated for > or = four weeks by bowel rest and nasogastric tube feeding of an oligopeptide or amino acid based formula. At first follow up visit, remission (fall in Paediatric Crohn9s Disease Activity Index, PCDAI to

Journal ArticleDOI
Isao Okayasu1, Toshifumi Ohkusa, K Kajiura, Jun Kanno, S Sakamoto 
01 Jul 1996-Gut
TL;DR: Repeated mucosal erosion with necrosis and regeneration is critical for the development of colorectal tumours in this experimental colitis system.
Abstract: BACKGROUND: The mechanisms underlying the frequent development of colorectal carcinomas in patients with ulcerative colitis are still unknown. AIMS: To evaluate whether mucosal necrosis and regeneration act as enhancing or promoting factors in colorectal tumorigenesis, development of multiple colorectal tumours was studied in a murine model of ulcerative colitis with azoxymethane pretreatment. METHODS: Periods of chronic ulcerative colitis in mice were induced by three repeated administrations of 3% dextran sulphate sodium subsequent to a single azoxymethane pretreatment, to give conditions similar to the clinically observed active and remission phases. RESULTS: In the chronic colitis group with carcinogen exposure, multiple mucosal tumours (10.5/mouse) developed in the colorectum. This occurred primarily on the left side of the large intestine or transverse colon, the sites of the most severe colitic injury. The observed lesions were high grade dysplasias and invasive adenocarcinomas. Increased cell proliferation was evidenced by high uptake of bromodeoxyuridine, and increased activities of thymidylate synthetase and thymidine kinase. No tumours were induced in the control groups with azoxymethane pretreatment or chronic colitis alone. CONCLUSIONS: Repeated mucosal erosion with necrosis and regeneration is critical for the development of colorectal tumours in this experimental colitis system.

Journal ArticleDOI
01 Nov 1996-Gut
TL;DR: These findings challenge current concepts of the development of Helicobacter induced atrophy in that active chronic gastritis of antrum or the body mucosa, or both, is not a prerequisite and suggest an autoimmune basis for the pathology.
Abstract: BACKGROUND/AIMS: The role of host factors has been neglected in studies of the pathogenesis of Helicobacter associated disease. The aim of this study was to assess the response of different mouse strains to infection with a single strain of Helicobacter felis. METHOD: Six strains of inbred mice were infected with the identical H felis culture and were killed at one month, two months, and six months after infection to assess histopathological changes. In addition, two strains of mice were infected with a mouse adapted strain of H pylori and examined at six months after infection. RESULTS: In SJL, C3H/He, DBA/2, and C57BL/6 infected mice, severe to moderate chronic active gastritis was observed only in the body of the stomach, which increased in severity over time with specialised cells in the body glands being replaced. As the severity of this damage in the body increased and atrophic changes were seen, the level of bacterial colonisation of the antrum decreased. In contrast, in BALB/c and CBA mice, there was only mild gastritis in the antrum, no remarkable changes were detected in their body mucosa, and no atrophy was seen over time. In both these strains of mice, heavy bacterial colonisation was seen, which tended to increase over the period of the experiment. Of particular importance in this experiment was that bacterial colonisation was mainly restricted to the antrum yet the atrophy, when present, was only observed in the body of the stomach. H pylori infected C3H/He mice showed moderate colonisation of the antrum, which persisted up to six months with little development of atrophy. In contrast, H pylori in C57BL/6 mice showed excellent colonisation of the antrum at two months but six months after infection there was moderate to severe body atrophy, which was associated with a loss of bacteria from the antrum. CONCLUSIONS: These findings challenge current concepts of the development of Helicobacter induced atrophy in that active chronic gastritis of antrum or the body mucosa, or both, is not a prerequisite. They also suggest an autoimmune basis for the pathology although no autoantibody or antibody to the H+/K+ ATPase was detected. Loss of infecting helicobacters from the stomach together with development of an atrophic gastritis in the body of the stomach is similar to the pattern found in certain H pylori infected human subjects.

Journal ArticleDOI
01 Nov 1996-Gut
TL;DR: Increased acid secretion after a conventional treatment period with a proton pump inhibitor is probably due to ECL cell hyperplasia and may have negative consequences for acid related diseases.
Abstract: BACKGROUND: In contrast with the histamine2 (H2) blockers, proton pump inhibitors have not been shown to give rebound hypersecretion of acid. Taking into consideration the hyperplasia of the enterochromaffin-like (ECL) cell provoked by hypergastrinaemia secondary to profound acid inhibition and the central role of histamine from ECL cells in the regulation of acid secretion, the lack of any rebound acid hypersecretion after treatment with proton pump inhibitors has been questioned. AIMS: To reassess the effect of treatment with omeprazole on post-treatment acid secretion. METHODS AND PATIENTS: Basal and pentagastrin stimulated acid secretion were determined in nine patients with reflux oesophagitis before and 14 days after termination of a 90 day treatment period with the proton pump inhibitor omeprazole (40 mg daily). Basal gastrin release were determined before and during omeprazole treatment. Furthermore, biopsy samples from the oxyntic mucosa were taken before and at the end of the treatment period for chemical (histamine and chromogranin A (CgA)) evaluation of the ECL cell mass. RESULTS: A substantial increase in meal stimulated gastrin release during omeprazole treatment resulted in an increased ECL cell mass. Furthermore, CgA in serum increased during omeprazole treatment suggesting that serum CgA may be used as a test to evaluate ECL cell hyperplasia. A significant increase in basal and a marked (50%) and significant increase in pentagastrin stimulated acid secretion were found after treatment with omeprazole. CONCLUSIONS: Increased acid secretion after a conventional treatment period with a proton pump inhibitor is probably due to ECL cell hyperplasia and may have negative consequences for acid related diseases.

Journal ArticleDOI
01 May 1996-Gut
TL;DR: The differences in age of onset between parents and children are not readily explained by a simple cohort effect or ascertainment bias, and may reflect effects of genetic factors, producing anticipation between generations.
Abstract: BACKGROUND--Although many recent studies have shown the increased risk of inflammatory bowel disease in relatives of patients with Crohn's disease and ulcerative colitis, clinical patterns of disease within families remain relatively poorly documented. AIMS--In this study, clinical characteristics (disease type, extent, age on onset, need for surgery, and presence of extraintestinal manifestations) have been compared in affected subjects in multiply-affected families, with inflammatory bowel disease. METHODS--54 families in whom one parent and at least one child were affected (a total of 77 parent-child pairs) and 155 families in whom at least two siblings were affected (a total of 190 affected sibling pairs) were involved. RESULTS--In affected parent-child pairs, parent and child were concordant for disease type in 58 of 77 pairs (75.3%), for extent in 63.6%, extraintestinal manifestations in 70.1%, and smoking history in 85%. The median age of onset in parents was significantly higher than offspring (p < 0.0001). In 40 pairs, 60.6%, the parent was at least 10 years older than child. Siblings were concordant for disease type in 81.6% of the affected sibling pairs, extent in 76.0%, extraintestinal manifestations in 83.8%, and smoking history in 81.3%. In contrast with the parent-child pairs, 68.1% (111 sibling pairs) siblings were diagnosed within 10 years of each other. The median age of onset was 24.0 years. CONCLUSIONS--This study has shown consistent clinical patterns in many families with inflammatory bowel disease. The differences in age of onset between parents and children are not readily explained by a simple cohort effect or ascertainment bias, and may reflect effects of genetic factors, producing anticipation between generations.

Journal ArticleDOI
01 Mar 1996-Gut
TL;DR: It is concluded that both immunological unresponsiveness and preferential coating with IgA are responsible for the relative absence of colonic mucosal inflammation.
Abstract: The bacterial flora in the human colon, although extremely diverse, has a relatively stable composition and non-infectious anaerobic bacteria are dominant. The flora forms a pool of numerous different antigens separated from mucosal immunocompetent cells by just a single layer of epithelial cells. Despite this thin barrier, however, the colonic mucosa is physiologically only mildly inflamed. This study looked at the mucosal humoral immune response against faecal anaerobes. By flow cytometric analysis the in vivo immunoglobulin coating of anaerobic bacteria in faecal samples of 22 healthy human volunteers was determined. In a previous study flow cytometric analysis of faecal bacteria has been found to be a very sensitive method to detect immunoglobulins on faecal bacteria. This technique showed that in vivo many bacteria are coated with IgA (24-74%) and less with IgG and IgM. The presence of many bacteria coated with IgA implies that IgA coating does not result in permanent removal of the species from the colon. The absence of immunoglobulin coating suggests that there is immunological unresponsiveness for anaerobic bacterial antigens. It is concluded that both immunological unresponsiveness and preferential coating with IgA are responsible for the relative absence of colonic mucosal inflammation.

Journal ArticleDOI
01 Mar 1996-Gut
TL;DR: Low bone mineral density in patients with untreated coeliac disease increases rapidly when treatment with a gluten free diet is followed, and the importance of early diagnosis and treatment in all patients with coleiac disease is emphasised.
Abstract: To evaluate the effects of a gluten free diet on bone mineral density in untreated adult patients with coeliac disease, 63 patients (17-79 years, 35 women) were examined at diagnosis and after one year taking a gluten free diet. Bone mineral density was measured in the forearm using single photo absorptiometry and in the lumbar spine, femoral neck, and trochanter using dual energy x ray absorptiometry. The values for each patient were compared with those of 25 healthy controls, matched for sex, age, and menopausal state. Before being given a gluten free diet bone mineral density in the total group was reduced at all sites (p < 0.001). Age adjusted bone mineral density was inversely correlated with age. During the first year taking a gluten free diet bone mineral density increased at all sites (p < 0.01). This was seen in patients of all ages and in patients who were without symptoms of malabsorption (weight loss or diarrhoea) before treatment. Low bone mineral density in patients with untreated coeliac disease increases rapidly when treatment with a gluten free diet is followed. These findings emphasise the importance of early diagnosis and treatment in all patients with coeliac disease.