Perceived food intolerance in subjects with irritable bowel syndrome-- etiology, prevalence and consequences.

OBJECTIVES: This study estimates the prevalence of perceived food intolerance and its consequences in subjects with irritable bowel syndrome (IBS), evaluates the utility of common tests for food intolerance, studies the relation between perceived food intolerance and other disorders, and discusses the etiology. DESIGN: Cross-sectional study. SETTING: National health survey. SUBJECTS: A selection of the population (n=11,078) in Oppland county, Norway, was invited to a health screening, and a sample of subjects with IBS were included in the study. INTERVENTIONS: A medical history of food intolerance, musculoskeletal pain, mood disorders and abdominal complaints was taken, and tests were performed for food allergy and malabsorption. A dietician evaluated the dietary habits of the subjects. RESULTS: Out of 4,622 subjects with adequately filled-in questionnaires, 84 were included in the study, 59 (70%) had symptoms related to intake of food, 62% limited or excluded food items from the diet and 12% had an inadequate diet. The mean numbers of food items related to symptoms and the number of foods limited or excluded from the diet were 4.8 and 2.5, respectively. There were no associations between the tests for food allergy and malabsorption and perceived food intolerance. Perceived food intolerance was unrelated to musculoskeletal pain and mood disorders. CONCLUSIONS: Perceived food intolerance is a common problem with significant nutritional consequences in a population with IBS. The uselessness of current antibody tests and tests for malabsorption and the lack of correlation to psychiatric co-morbidity make the etiology obscure.

The value of a general therapeutic approach in subjects with irritable bowel syndrome.

BACKGROUND: The general therapeutic approach is the cornerstone in the management of irritable bowel syndrome, but the effect is poorly documented. AIM: To evaluate the effect of the general therapeutic approach for irritable bowel syndrome. METHODS: Subjects with irritable bowel syndrome identified in a public screening were included. Scores for abdominal symptom (range 0-12), musculoskeletal pain and mood disorders were calculated. After exclusion of other disorders, a doctor presented irritable bowel syndrome as a positive diagnosis, gave information, reassurance and lifestyle advice, but no pharmacotherapy. A dietician gave dietary advice. There was a follow-up after 6 months. RESULTS: Sixty-five persons (females/males: 44/21) with mean age 49 years (range 31-76) were included, 31 (48%) were recommended dietary changes. Twenty subjects (31%) had satisfactory relief of symptoms after 6 months. The scores for abdominal symptom was reduced from 3.1 to 2.2 (P = 0.007), the reduction was 2.2 in the diarrhoea-predominant group given advice compared with 0.4 in the other subjects (P = 0.035). Previous consultations for the complaints, visits for psychiatric disorders, and presence of mood disorders were predictors of persistent complaints. CONCLUSIONS: There was a significant relief of symptoms after 6 months, those with psychological co-morbidity responded less well. The effect of dietary advice was only seen in those with diarrhoea-predominant irritable bowel syndrome.

Mesalazine 4 g daily given as prolonged-release granules twice daily and four times daily is at least as effective as prolonged-release tablets four times daily in patients with ulcerative colitis.

BACKGROUND: High doses of mesalazine usually result in an inconvenient dosage schedule and reduced compliance. The goal of this trial was to compare the effects of mesalazine 4 g daily given as prolonged-release granules in packets of 1 g with that of prolonged-release tablets of 0.5 g. METHODS: Two hundred twenty-seven patients with mild-to-moderate ulcerative colitis were randomized to treatment with two packets twice daily (Gr-b.i.d.), 1 packet four times daily (Gr-q.i.d.) or 2 tablets four times daily (Ta-q.i.d.) for 8 weeks. A disease activity index (ulcerative colitis disease activity index: UC-DAI) was calculated, and the granules were defined as noninferior to the tablets if the lower limit of the 95% CI for the differences was more than -1 UC-DAI score unit. RESULTS: Noninferiority of the granules compared with the tablets was demonstrated. The mean improvement in the UC-DAI in the treatment groups Gr-b.i.d., Gr-q.i.d., and Ta-q.i.d. were 3.2, 2.9, and 2.4, respectively; the proportion of complete responders in the three groups 39%, 37%, and 31%, respectively. There were no differences in side effects. CONCLUSION: Mesalazine 4 g daily given as prolonged-release granules twice and four times daily is at least as effective as prolonged-release tablets four times daily in patients with mild to moderate ulcerative colitis. The patients preferred the twice daily dosing.

Compliance with anti-ulcer medication during short-term healing phase clinical trials.

Nine hundred and sixty-six patients' compliance with drug therapy of peptic ulcerations and reflux oesophagitis in four clinical trials were studied. The mean compliance rates varied from 90.5% (95% C.I. 89.0-92.1%) to 99.2% (95% C.I. 98.2-100.1%). Compliance declined significantly with increasing complexity of the dosage schedule in all trials, and toward the end of the treatment period in two of them. Patients with adverse events had a significant drop in compliance during the last part of the treatment period in one of the trials. There was a significant inter-centre variation in compliance. Overall, the variation was of little clinical significance. Patient compliance was independent of age, sex, use of alcohol and tobacco, effect of treatment, concomitant drug therapy and whether the pill was active drug or placebo. The study shows that a simplified dosage schedule, shortening of the treatment period, use of drugs with minimal side-effects, and meticulous selection of centres could improve patient compliance with drug therapy in clinical trials.

Comorbidity of irritable bowel syndrome in general practice: a striking feature with clinical implications.

BACKGROUND: Somatic comorbid symptoms might identify irritable bowel syndrome patients with different aetiologies and needs of treatment. AIMS: To measure comorbid symptoms in patients with irritable bowel syndrome in general practice, and to explore characteristics of patients with low, intermediate and high somatic comorbidity. METHODS: Prospective study of 208 of 278 consecutive patients with irritable bowel syndrome (Rome II) in nine general practices. Questionnaires assessed 22 comorbid symptoms (subjective health complaint inventory), psychosocial factors including psychological distress (Symptom Check list-10) and quality of life (Short form-12). Subjective health complaint data from 1240 adults (controls) constituted a reference material. Patients with low, intermediate and high somatic comorbidity were identified by a somatic comorbidity score (17 subjective health complaint items). Health care seeking was assessed after 6-9 months. RESULTS: Patients with irritable bowel syndrome (67% females, mean age 50, s.d. 16) reported 20 of 22 comorbid symptoms significantly more frequent than controls (odds ratios = 2-7, P < 0.001). The somatic comorbidity score correlated with psychological distress (R = 0.46, P < 0.001). Patients with high somatic comorbidity reported higher levels of mood disorder, health anxiety, neuroticism, adverse life events and reduced quality of life and increased health care seeking when compared to those with low and intermediate somatic comorbidity (P-values < 0.05). CONCLUSIONS: Our findings support the hypothesis that structured assessment of comorbid somatic symptoms might identify subgroups with different aetiology and needs of treatment.

Patient compliance with intensive antacid treatment. A multi-centre study.

Patient compliance with respect to a liquid antacid (Novaluzid) was examined in an open multicentre study. The study included 186 patients with various upper gastrointestinal conditions. The patients were randomly assigned to either 2 or 4 weeks' treatment with 10 ml Novaluzid 1 and 3 hours after each meal and at bedtime. They were not informed that they were taking part in a study. The compliance was high, with no difference between the two groups; 82% and 79%, respectively, and showed no dependency on patient age, diagnosis or previous use of antacids.

Zaltidine: an effective but hepatotoxic H2-receptor antagonist.

Zaltidine is a new H2-receptor antagonist. This study compares the safety and efficacy of zaltidine with those of placebo in the short-term treatment of duodenal ulcer. One hundred and thirty-five patients were randomly allocated to 4 weeks' treatment with either 150 mg zaltidine once daily or placebo. Fifty-nine were treated for a full 4 weeks with zaltidine before the trial was stopped. Healing rates after 4 weeks of zaltidine and placebo were 86% and 19%, respectively (p less than 0.001). Five patients in the zaltidine group had increased serum aminotransferase levels at the final (4-week) visit. The values normalized when treatment was stopped. Liver biopsy specimens provide strong evidence of drug-induced injury. Hepatic damage was associated with plasma levels of zaltidine in the upper half of the observed range. Zaltidine appears to be an effective treatment of duodenal ulcer. However, the incidence of hepatic damage (8%) seems higher than with commonly used H2-receptor antagonists.

Idiopathic Hypoparathyroidism and Hyperthyroidism.

A case of idiopathic hypoparathyroidism is reported. The patient had presented symptoms for 16 years and various treatments and diagnoses had been tried before the correct conclusion was reached. Adequate treatment resulted in normalization of most of the symptoms. The patient also had hyperthyroidism, an exceptional combination. A possible relationship between the two diseases is discussed.

Collaboration by use of the Internet yields data of high quality and detects non-uniform management of patients with Helicobacter pylori infection.

BACKGROUND: The benefits of new technology steadily being introduced in medicine should be documented. In this study, remote entry of a set of data from the daily routine was submitted via the Internet to a common database. The usefulness and quality of the information are evaluated. METHODS: Fourteen hospitals reported a common data set on consecutive Hp+ve patients handled in accordance with daily practice. Participants submitted their data via the Internet to a database. There was no monitoring or other surveillance. No audit was planned or expected, but was nevertheless possible. Doctor compliance with the common agreement was checked, differences in medical practice were noted and quality was assessed comparing the most important source data with the data in the final database. RESULTS: Four-hundred-and-forty patients were included. The quality of the reported data was high, only 1.3% showing a discrepancy between source data and the database. Overall treatment success was 89%, with no significant differences between hospitals. There were significant differences in clinical practice between the centres, the proportion of patients treated for ulcer disease varying from 36% to 96% (P < 0.001). Doctor compliance with the agreed collaboration varied significantly (P < 0.001). CONCLUSION: Internet collaboration through remote data entry in a common database yields data of high quality without monitoring, and is a powerful and resource economic tool for clinical multicentre trials and quality assurance.

Sphincter of Oddi dysfunction. Dynamic cholescintigraphy and endoscopic retrograde cholangiopancreatography with papillotomy in diagnosis, treatment, and follow-up study.

The study compares dynamic cholescintigraphy with traditional methods in diagnosing sphincter of Oddi dysfunction. Five patients with dysfunction of the sphincter, in accordance with traditional diagnostic criteria, are compared with 25 patients with postcholecystectomy syndrome. Dynamic cholescintigraphy showed complete separation of the two groups, T1/2 distinguishing better than Tmax. The patients with sphincter dysfunction were treated with endoscopic papillotomy (EPT) for symptomatic relief. Three had early complications. At follow-up study the courses were uneventful. Their symptoms had disappeared or markedly improved, and dynamic cholescintigraphy was normalized. In conclusion, dynamic cholescintigraphy seems to be a reliable noninvasive method for identification and control of patients with sphincter of Oddi dysfunction suitable for treatment with EPT.

Does short-term treatment with proton pump inhibitors cause rebound aggravation of symptoms?

BACKGROUND: Rebound acid hypersecretion might occur after treatment with proton pump inhibitors. This study looks for a rebound aggravation of symptoms after short-term treatment with lansoprazole. STUDY: Sixty-two patients (19 men and 43 women; mean age, 54 years; range, 32-77 years) with heartburn and regurgitation and normal upper endoscopy findings were studied in a randomized, double-blind, placebo-controlled trial with a crossover design. There were two 5-day treatment periods with lansoprazole 60 mg once daily or placebo in random order, separated by a 9-day washout period. Reflux, total, and antacid scores were calculated for each of the treatment periods. Higher scores during the placebo period in the group given lansoprazole first than in the group given placebo first indicated a rebound aggravation of symptoms. RESULTS: The mean symptom scores during the placebo period in the groups given lansoprazole first and placebo first were as follows: reflux score, 21.5 and 17.6, respectively (not significant); total score, 11.2 and 10.3, respectively (not significant); and antacid score, 8.2 and 7.2, respectively (not significant). CONCLUSIONS: There is no indication of a rebound aggravation of symptoms 12 to 14 days after a 5-day treatment with lansoprazole 60 mg once daily in patients with reflux symptoms.

Long-term treatment with 300 mg ranitidine once daily after dilatation of peptic oesophageal strictures.

This clinical, double-blind, multicentre trial evaluates the long-term effect of ranitidine in patients dilated for peptic oesophageal strictures. Seventy-one consecutive outpatients were dilated with hydrostatic balloons to a diameter of 18-20 mm and randomized to a 1-year treatment with 300 mg ranitidine in the evening or with placebo. Endoscopies with measurement of the stricture size were performed before the initial dilatation, after 6 and 12 months, and in between when necessary. Symptoms and use of antacids were registered at inclusion and after 3, 6, 9, and 12 months. Thirteen patients were withdrawn before study end point. Fifteen of 30 (50%) in the ranitidine group and 11 of 28 (39.3%) in the placebo group were redilated. The difference in disfavour of ranitidine was 10.7% (95% confidence interval, -14.9; 36.2%). Nor were there any statistically significant differences between the treatment groups with regard to stricture size at end point, symptoms, or use of antacids. In conclusion, there is no evidence of any clinically significant effect of a 1-year treatment with 300 mg ranitidine once daily after dilatation of peptic oesophageal strictures.

Ranitidine effectively relieves symptoms in a subset of patients with functional dyspepsia.

BACKGROUND: Acid secretion inhibitors are of dubious value to most patients with functional dyspepsia but might be effective in a subset. The aims of the trial were to compare the effect of ranitidine with that of placebo in selected subsets of patients. METHODS: Two hundred and twenty-six patients with functional dyspepsia were included in a double-blind multi-crossover (MCO) trial. After 6 weeks an effect score (Xs) with a range of 0-5 was calculated. They were then stratified in accordance with their score and randomized to 4 weeks' double-blind treatment with ranitidine or placebo. Overall symptoms were scored on a 100-mm visual analogue scale, and the change in score (measured in millimetres) was the primary effect measure. RESULTS: Two hundred and six patients completed the study. The effect of ranitidine and placebo in the 'responders' (76 patients with Xs of 4-5 after the MCO period) was 28 mm and 5 mm, respectively (P < 0.001), and in all patients 19 mm and 12 mm, respectively (P < 0.03). No effect was seen in 'nonresponders' (130 patients with Xs of 0-3 after the MCO period). The clinical improvement, as judged by the patients given ranitidine during the last 4-week period was statistically significantly different in favour of responders compared with nonresponders. We were unable to characterize the responders on the basis of demographics, symptoms, and signs. CONCLUSIONS: Ranitidine has a good and clinically significant effect in a subset of patients with functional dyspepsia.

Effect of cisapride on symptoms and biliary drainage in patients with postcholecystectomy syndrome.

The study evaluates the effect of 20 mg cisapride twice daily on symptoms and biliary drainage in patients with the postcholecystectomy syndrome. Nineteen patients, all female, went through a randomized, double-blind, placebo-controlled, crossover trial with two 4-week treatment periods separated by a 2-week washout period. Symptoms were registered on diary cards. Biliary drainage was studied with dynamic cholescintigraphy. The down slope of the time-activity curve (T1/2 and elimination index) was used as a measure of the biliary drainage. More symptoms were registered during cisapride therapy than with placebo. This unfavourable effect of cisapride was statistically significant in a subgroup of patients with postcholecystectomy complaints identical to the biliary pain they experienced during injection of contrast at the endoscopic retrograde cholangiopancreatographic examination. Cisapride statistically significantly hastened biliary drainage. The median T1/2 values were 24 and 28 min after cisapride and placebo, respectively (p less than 0.01). In conclusion, cisapride promoted biliary drainage in patients with the postcholecystectomy syndrome but had an unfavourable symptomatic effect in those with bile duct-triggered postcholecystectomy complaints.

Patients with functional dyspepsia responding to omeprazole have a characteristic gastro-oesophageal reflux pattern.

BACKGROUND: The effect of acid secretion inhibitors in patients with functional dyspepsia (FD) is equivocal. One previous trial showed an effect in patients with a characteristic gastro-oesophageal reflux pattern. This double-blind trial compares the number of reflux episodes in responders and non-responders to omeprazole. METHODS: Twenty-four patients (men/women, 11:13; mean age, 49 years) with FD were included; those with reflux as the main symptom were excluded. An upper endoscopy and a 24-h oesophageal pH measurement were performed before randomization to treatment with 10-20 mg omeprazole or placebo for 4 weeks. Patients who at questioning considered themselves to have achieved sufficient relief of dyspeptic symptoms after 4 weeks were characterized as responders. RESULTS: The number of responders in the omeprazole and placebo groups was 8 of 14 (57%) and 2 of 10 (20%), respectively (P = 0.07). The mean number of reflux episodes at the 24-h oesophageal pH measurement in responders and non-responders to omeprazole was 57 and 25, respectively (P < 0.003). In the omeprazole group the number of responders was 0 of 5 (0%) in those with < 32 reflux episodes and 8 of 9 (89%) in those with > 32 reflux episodes (P < 0.003). CONCLUSION: Patients with FD responding to omeprazole were characterized by many reflux episodes.

Diagnosing irritable bowel syndrome: poor agreement between general practitioners and the Rome II criteria.

BACKGROUND: The new guidelines for diagnosing irritable bowel syndrome (IBS) in clinical practice recommend the use of the Rome II criteria. In this study the agreement between general practitioners (GPs) and the Rome II criteria for diagnosing of IBS and functional bowel disorders (FBD) is examined. METHODS: Consecutive patients in general practice were asked to report on abdominal complaints, for which they had consulted or wanted to consult a GP. Patients with such complaints completed a questionnaire based on the Rome II criteria for FBD. After consultations, the GPs reported their diagnoses on the abdominal complaints. RESULTS: Of 3097 screened patients, 553 patients were diagnosed by their GP and had complete data in the questionnaire. Of these patients, 107 had IBS according to the GPs and 209 had IBS according to the Rome II criteria (agreement 58%, kappa 0.01 (CI: -0.06; 0.09)). Agreement on IBS and FBD in patients without organic disease, without reflux or dyspepsia and in patients with a verified diagnosis was 45%-58%, with kappa values from -0.02 to 0.13. IBS and FBD cases were diagnosed by the Rome II criteria more often than by the GPs in all these groups of patients (P < 0.001). In patients with diagnostic discrepancies concerning IBS, 'stress-related symptoms' was predictive of a diagnosis of IBS made by the GPs only (OR 2.17 (CI: 1.1; 4.2)). CONCLUSIONS: This study shows poor agreement in the diagnosis of IBS between GPs and the Rome II criteria. Therefore, current knowledge about IBS based on strict criteria is not necessarily transferable to patients with IBS in general practice.

Ranitidine for non-ulcer dyspepsia. A clinical study of the symptomatic effect of ranitidine and a classification and characterization of the responders to treatment.

Seven Norwegian centres recruited 61 female and 54 male patients with non-ulcer dyspepsia (NUD). Their mean age was 40 years. After 6 weeks' double-blind alternating treatment with 150 mg ranitidine twice daily and placebo, 1 week of each alternative (part I), an effect score (Xs) and an efficacy index (Ei) were calculated. Ranitidine was significantly superior to placebo for symptomatic relief (p less than 0.01). Twenty-eight, 49, and 38 patients were Xs-classified as 'responders', 'unclassified', and 'nonresponders' to ranitidine, respectively. The symptomatic effect was impressive in the responder group and moderate but significant also in the unclassified group. The nonresponders had a significantly unfavourable effect of ranitidine compared with placebo. The Xs-classified responders and unclassified continued single-blind treatment with ranitidine for 4 weeks (part II) and were reclassified as 'new responders/nonresponders'. The new responders received single-blind treatment with placebo until relapse or maximum 8 weeks (part III). Parts II and III verified the good Xs classification of responders to ranitidine treatment. The overall effect of ranitidine in patients with NUD was due to good symptomatic effect in a subpopulation characterized by meal-related heartburn and/or regurgitation, large body mass index, first-degree relatives with gastrointestinal diseases, a relatively low frequency of gastrointestinal symptoms per week, and absence of soft stools.

Lactose malabsorption in a population with irritable bowel syndrome: prevalence and symptoms. A case-control study.

BACKGROUND: Symptoms after intake of milk are common in persons with irritable bowel syndrome (IBS). The aims of this study were to compare the prevalence of lactose malabsorption (LM) and symptoms related to intake of milk and lactose in subjects with IBS with that of healthy volunteers, and to search for symptoms that are characteristic of LM. METHODS: A case-control study in a Norwegian population was initiated. Subjects with IBS were asked for symptoms related to intake of milk and lactose, tested for LM, and compared with a group of healthy volunteers. RESULTS: The study comprised a total of 187 persons (82 with IBS and 105 volunteers), females/males: 138/49, mean age 47 years. In subjects with IBS and in healthy volunteers, LM was present in 3/74 (4.1%) and 4/105 (3.8%), respectively (ns), milk-related symptoms in 32/79 (40%) and 13/105 (12%), respectively (P < 0.001) and symptoms after intake of lactose in 28/74 (38%) and 21/104 (20%), respectively (P=0.01). Borborygmi starting within 5 h after intake of lactose and lasting for more than 2 h indicated LM (OR 61 (95% CI: 8-475), P < 0.001). CONCLUSIONS: IBS and LM are unrelated disorders in a Norwegian population. Milk-related symptoms and symptoms after intake of lactose are unreliable predictors for LM. Precise symptom-based criteria might enhance the diagnostic accuracy for LM.

The natural restricturing process after dilatation of peptic esophageal strictures.

The study analyzes the natural esophageal restricturing process after dilatation of peptic esophageal strictures. Fifty patients (male/female: 30/20) with median age 71 years (range 20-87) with peptic esophageal strictures were dilated with hydrostatic balloons to 20 mm and followed up for 12 months. Stricture size was measured with a 'balloon pull-through' technique before the dilatations, and at follow-ups after 6 and 12 months. The restricturing rate was defined as the difference in stricture diameter at two measurements divided by the time interval. The mean restricturing rate during the first and last 6 month periods were 0.99 and 0.02 mm/month respectively (P < 0.001), and during the first 6 months the restricturing rates were 1.98 and 0.69 mm/month in patients redilated and not redilated respectively (P < 0.001). A tight stricture at the initial dilatation, a long history of reflux symptoms and a short history of dysphagia were all significantly related to a high restricturing during the first 6 months (P < 0.001).