[Dietary treatment of celiac disease]. / Kostbehandling ved cøliaki.

Life-long gluten-free diet is the established therapy of coeliac disease. Patients suffering from dermatitis herpetiformis benefit from the same treatment. In Norway the gluten-free diet has excluded oats as well as wheat, rye and barley. The basis for this recommendation was a 1972 report indicating that ten out of 23 children consuming oats as part of their gluten-free diet for at least 18 months developed signs of damage to the intestinal mucosa. During the last decades, the clinical picture of coeliac disease has changed as a result of better diagnostic tools. Controlled clinical trials during the last few years indicate that some patients may tolerate small amounts of oats in their gluten-free diet. As a consequence, patients may be confused with regard to what dietary regime is recommended in coeliac disease. Compliance with gluten-free diet is important to secure growth and development, the all-round condition, fertility, bone density and a reduced risk of nutrient deficiency and malignancy. Consensus on dietary treatment is essential. A number of controlled trials are under way and the outcome of these studies will in a few years determine whether oats might be included in the standard gluten-free diet. So far oats are not recommended. The physician who makes the diagnosis is responsible for all patients getting adequate dietary counselling and management. Dietary advice given by health personnel must be consistent.

[Guidelines for diagnosis and follow-up of patients with celiac disease. Norwegian Coeliac Association]. / Retningslinjer for diagnose og oppfølging av cøliaki.

The incidence and prevalence of coeliac disease in Norway is probably much higher than previously recognized. A prevalence of 1 per 676 individuals has been reported among adults in Norway. A much higher incidence has been documented in Sweden, both among children (one per approximately 300 liveborns) and among adults (1:256 healthy blood donors). Similar prevalence figures have been reported from Italy among young students. Eight new, biopsy-proven cases of coeliac disease were recently found by screening 2296 blood donors in Bergen (1:287). The symptoms of coeliac disease are often vague. Oligo- and asymptomatic cases often occur. The advisory council of the Norwegian Coeliac Association has established guidelines for the diagnostic work-up and for follow-up of patients with coeliac disease, in order to raise awareness of the disease, achieve a standardized work-up procedure and improve follow-up.

The natural course of peptic ulcer disease and its predictors.

BACKGROUND: Little is known about today's natural course of peptic ulcer disease (PUD). METHODS: A follow-up study based on a structured telephone interview was attempted in 728 patients with an endoscopic diagnosis of peptic ulcer in 1980-84. RESULTS: Seven patients (1%) died because of PUD during the 8- to 10-year follow-up period. Of the 441 interviewed patients 15.2% had experienced no further clinical manifestations of PUD, 10.9% had had bleeding and 0.7% perforation, and 17.5% had been operated on. The operated patients reported fewer symptoms (p < 0.01) during the last 2 weeks before the interview than those not operated on. On an average the unoperated patients had had symptoms and had used histamine-2-receptor antagonists (H2RA) 12 and 10 weeks per year, respectively. Long-term treatment with H2RA was reported by 18%. More than one-third (36%) of the unoperated patients stated that the symptoms had had a significant negative impact on their lives. Age at onset of disease and index ulcer, family history, use of anti-inflammatory drugs and alcohol, bleeding, and another chronic disease were found to be significant predictors of the course. CONCLUSION: In more than one-third of the patients with PUD the course is still burdened with many symptoms and complications.

The intensity and variability of symptoms in dyspepsia.

During the waiting time for upper gastrointestinal endoscopy 165 patients with dyspepsia completed a questionnaire and a diary for daily measurements of the symptoms pain, heartburn, and global complaints. 23 patients (14%) had peptic ulcer disease (PUD), 18 oesophagitis (11%), and the rest were labelled nonulcer dyspepsia (NUD). NUD was further subdivided into ulcer-like, reflux-like, dysmotility, and essential NUD by means of predefined symptom profiles. 39 (24%) patients were on H2 receptor antagonist treatment. In general, the intensity of the daily symptoms was rather low, and except for a higher rating of heartburn in oesophagitis, there were no significant differences between PUD, oesophagitis, and NUD--treated or untreated. NUD patients with reflux-like dyspepsia had significantly more heartburn than the group with essential NUD; otherwise there were no differences between the subgroups of NUD. The individual daily ratings for abdominal pain, heartburn, and global symptoms varied by an average standard deviation of 64%, 97% and 47% of the mean values, respectively, and were independent of treatment or diagnoses. There was an approximately 40% probability that two successive days had different levels of symptoms. Only 10% of the patients showed stable symptoms, and the patients were completely symptom-free for 20% of the observation period. Symptoms in dyspepsia patients disclosed low intensity and high variability in this study. Such factors may be important sources of bias in clinical trials.

Can NSAIDs cause acute biliary pain with cholestasis?

Two patients had many acute episodes of biliary pain with elevated liver function tests 12-48 h after the last ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs) (including paracetamol) alone or in combination with codeine. One had known intolerance to NSAIDs, but paracetamol had not been previously incriminated in the pathogenesis of the attacks. In this patient the combined use of paracetamol and codeine probably also increased the severity of the episodes. We conclude that in some patients in whom endoscopic cholangiography is normal, biliary pain and abnormal liver function tests could be the result of NSAIDs. A thorough drug history is required in such cases.

Cimetidine on-demand in dyspepsia. Experience with randomized controlled single-subject trials.

Double-blind randomized controlled trials in single subjects (N of 1 RCTs) have demonstrated a beneficial symptomatic effect of cimetidine in reflux- or ulcer-like non-ulcer dyspepsia (NUD). However, spontaneous fluctuations in symptoms reduce the validity of such trials when performed as continuous trials with fixed dosages. This study was carried out to identify individual responders to cimetidine in NUD, peptic ulcer disease, and oesophagitis and to confirm the beneficial average effect of cimetidine in these clinical entities. We evaluated N of 1 multi-crossover trial designs, which compare the effects of single doses of cimetidine and placebo taken on-demand for symptomatic relief. Each trial consisted of six cimetidine (400 mg or 800 mg) and six placebo tablets randomized in successive pairs. The symptomatic effect of each tablet was measured 1/2-6 h after the intake. Outcomes were assessed by individual p values and confidence intervals. A minimal clinically important difference was defined, to assess the clinical significance as demonstrated by the confidence intervals. Thirteen of 25 patients (52%) with reflux- and ulcer-like NUD obtained individual p values below 0.20. Similarly, 7 of 9 patients (78%) with oesophagitis and 6 of 12 patients (50%) with peptic ulcer obtained such p values. On the basis of the 80% confidence intervals the corresponding numbers of subjects with clinically significant effect were six (NUD), three, and three. The combined data showed a significantly better effect of cimetidine than of placebo (p less than 0.0001) in each of the three diagnostic groups studied. Cimetidine taken on-demand may have a rapid symptom-relieving effect in dyspepsia.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between endoscopic hiatus hernia and gastroesophageal reflux symptoms.

Little is known about the relationship between hiatus hernia (HH) and gastroesophageal reflux symptoms (GERS). Nine hundred and thirty patients submitted to gastroscopy because of symptoms completed a self-administered questionnaire. Fourteen per cent showed esophagitis (ES) and 17% HH. Forty-nine per cent of the patients with HH had endoscopic ES, and 60% of those with ES had HH. The severity of ES was dependent (p less than 0.05) on both the presence and the size of HH. After exclusion of patients with peptic ulcer and malignancy, patients with and without HH and ES were compared with regard to the presence of single symptoms and a weighted GERS score based on symptoms proven to be typical for ES. Only borderline differences were found between patients with ES and HH and those with ES and no HH. The former group, however, presented with significantly (p less than 0.001) more GERS than the patients with HH only. Nevertheless, the patients with HH as the only pathologic finding had significantly (p less than 0.01) more GERS than the patients with no major endoscopic abnormality. This study indicates a close association between HH and gastroesophageal reflux disease and supports the clinical significance of an endoscopically detected HH.

The symptomatic effect of 1-day treatment periods with cimetidine in dyspepsia. Combined results from randomized, controlled, single-subject trials.

Before endoscopy a double-blind, randomized, controlled, single-subject trial comparing the symptomatic effect of 1-day treatment periods with cimetidine and placebo was conducted in patients with dyspepsia. Results from 339 patients were analysed. The trial lasted 12 days and consisted of 6 treatment days with 400 mg cimetidine three times daily and 6 days with placebo three times daily. The order of the treatments was randomized within six pairs, and a randomization test based on daily measures of global symptoms provided individual p values. Aggregation of the measures from all subjects showed that cimetidine alleviated the symptoms significantly better than placebo in peptic ulcer disease (PUD) (p less than 0.0001), oesophagitis (p less than 0.001), and non-ulcer dyspepsia (NUD) (p less than 0.0001). Twenty-seven per cent of the patients with PUD, 26% of those with oesophagitis, and 12% of the patients with NUD obtained individual p values of less than 0.10 and were defined as responders. The best predictors of the response to cimetidine in NUD were age above 40 years, heartburn or acid regurgitations being the worst symptom, and night pains relieved by food, milk, or antacids. In conclusion, the applied single-subject trial confirmed the overall symptomatic effect of cimetidine in dyspepsia and identified individual responders among patients with NUD with a clinically reasonable profile. The low proportion of responders among patients with PUD or oesophagitis suggests that the model has a low sensitivity for identification of individual responders and that the single-subject trial design in dyspepsia needs further refinement.

The predictive value of history in dyspepsia.

Symptomatic patients referred to an open-access upper gastrointestinal endoscopy completed a detailed, self-administered questionnaire aimed at assessing the predictive value of history in dyspepsia. Nine hundred and thirty patients were suitable for analysis. Of these, 29% were found to have organic dyspepsia. A substantial overlap of symptoms and demographic data was found among the various endoscopic diagnoses. Discriminating variables were identified by stepwise logistic regression analysis and included in predictive score models. Pain relieved by antacids, age above 40 years, previous peptic ulcer disease, male sex, symptoms provoked by berries, and night pain relieved by antacids and food were found to predict organic dyspepsia with a sensitivity and specificity of approximately 70%, when applied on the observed material. Similar probabilities were found for score models of peptic ulcer and esophagitis. In general, the low prevalence of organic diseases resulted in low positive and high negative predictive values. Accordingly, the main impact of the predictive models may be to reduce the number of negative endoscopies rather than to predict a precise diagnosis. Independent of disease category and age, 41% of the subjects expressed a fear of malignancy, emphasizing the value of reassurance from a negative endoscopy.

Effect of pancreatic enzymes in non-ulcer dyspepsia. A pilot study.

The symptomatic effect of pancreatic enzymes was examined in 37 patients with non-ulcer dyspepsia (NUD) recruited from general practice by means of a 24-day multicrossover model (MCOM) including six treatment periods and five regular interchanges between pancreatic enzymes and placebo. The evaluation was based on a comparison of the enzyme- and placebo-associated symptoms and on the number of times pancreatic enzymes were associated with less symptoms than the preceding or following placebo period in individual patients. No evidence of a short-term effect of pancreatic enzymes in NUD was found.

Low-dose antacids versus 400 mg cimetidine twice daily for reflux oesophagitis. A comparative, placebo-controlled, multicentre study.

Ninety-one patients with reflux oesophagitis were randomly allocated to treatment with one chewable antacid tablet (acid-neutralizing capacity, 30 mmol) four times daily, 400 mg cimetidine twice daily, or placebo. The study was double-blind, with a double-dummy technique. Endoscopy was performed before inclusion and after 8 weeks' treatment. Symptoms were recorded on diary cards and on visual analogue scales. Statistically significant healing of oesophagitis was achieved in all three treatment groups, but none of the active regimens were significantly superior to placebo. Symptoms were significantly reduced with both cimetidine and antacids compared with placebo. Patients taking antacids consumed significantly less extra antacids for pain relief and had significantly better global assessment score than patients taking cimetidine during the first and second half of the study, respectively. In conclusion, neither cimetidine nor antacids were significantly superior to placebo in healing of reflux oesophagitis. Both the active regimens were superior to placebo for symptomatic relief.

The benefit of colonoscopy.

In a prospective study involving 833 consecutive outpatient and open-access colonoscopies, attempts were made to characterize the benefit of colonoscopy in terms of both predicted and unpredicted findings and therapeutic procedures. The endoscopist therefore predicted the endoscopic findings before the endoscopy. The results were compared for the different indications for colonoscopy. The overall agreement between the predictions and the colonoscopic findings was 61%. Clinically significant abnormalities were found in about half the examinations. The most frequent abnormal findings were benign polyps (24%), inflammatory bowel disease (17%), and malignancy (5%). In about half the patients with a malignancy the indication for colonoscopy was rectal bleeding, and half of the malignancies were not predicted. The greatest benefit of colonoscopy was found in patients referred because of overt rectal bleeding or occult faecal blood, and abnormal barium enema or endoscopy findings. The importance of complete colonoscopy in connection with operation for colorectal carcinoma is emphasized.

Optimal assessment of gastrointestinal side effects induced by non-steroidal anti-inflammatory drugs. Endoscopic lesions, faecal blood loss, and symptoms not necessarily correlated, as observed after naproxen and oxindanac in healthy volunteers.

Gastrointestinal side effects caused by naproxen and oxindanac (a developmental non-steroidal anti-inflammatory drug) were compared by combined endoscopy and determination of faecal blood loss in 16 healthy male volunteers in a randomized, double-blind, crossover study. Individual daily faecal blood loss was determined by means of 51Cr-labelled erythrocytes. Gastroduodenoscopy was performed before and after administration of naproxen, 750 mg/day, and oxindanac, 600 mg/day, for 1 week each. A washout period of at least 3 weeks was inserted between drug periods. Visual analogue scales (VAS) were used for endoscopic assessment of lesions and subjective complaints. Mean faecal blood loss increased from a base line 0.48 ml/24 h to 1.59 ml/24 h with naproxen (p less than 0.01) and from 0.56 ml/24 h to 1.31 ml/24 h with oxindanac (p less than 0.01). VAS scores for gastroduodenal lesions increased significantly with both drugs. Naproxen caused a significantly greater increase than oxindanac (p less than 0.05). There was no correlation between gastrointestinal blood loss and endoscopic findings. Subjective symptoms were correlated to faecal blood loss with naproxen, but not to endoscopic findings. No such correlations were observed for oxindanac. Naproxen caused a significant prolongation of bleeding time (p less than 0.01), whereas the increase caused by oxindanac was not significant (p = 0.09).

Low-dose antacids or cimetidine for duodenal ulcer?

In a double-blind, randomized, multicenter trial 150 consecutive outpatients with endoscopically verified duodenal ulcer were treated with either a low-dose antacid regimen (1 tablet q.i.d.; acid-neutralizing capacity, 120 mmol/day), or cimetidine (800 mg nocte). After 4 wk of treatment control gastroscopy showed ulcer healing in 54 of 76 patients (71.1%) in the antacid group, as compared with 58 of 74 patients (78.4%) in the cimetidine-treated group. The difference in healing rate of 7.3% (95% confidence interval, -6.5% to +21.1%) was not statistically significant. The symptomatic effect, measured as number of days and nights with ulcer pain, was also quite similar in the two treatment groups. However, the number of days with pain was significantly lower in the first week of treatment in the antacid group (p less than 0.01). Thus, the efficacy of a low-dose antacid tablet regimen approximated that of cimetidine (800 mg nocte) in the treatment of duodenal ulcer patients.

Do we need to listen to the patient? The predictive value of symptoms.

We have previously shown that the endoscopist is able to predict the endoscopic diagnosis in about two thirds of the patients. We report some preliminary findings from two different studies on the ability of symptoms to predict endoscopic findings. Comparison with similar studies in Glasgow and Huddinge suggests that the predictive value of symptoms probably varies between countries and depends on the population dealt with as well as on the methods used for symptom evaluation. Predictive models for peptic ulcer or endoscopic esophagitis based on symptoms showed at best an about 60-70% sensitivity and specificity. We strongly feel that future studies on the predictive value of symptoms should be more focused on the first step in the decision process in general practice.

Screening for occult faecal blood loss in a community by means of Hemoccult II slides and a tetramethylbenzidine test.

A total of 754 persons statistically selected from the age group 54-64 years were asked by letter to provide faecal samples for screening of occult blood during dietary restrictions. A total of 413 persons (55%) returned an average of 5.8 (range, 1-6) faecal samples each. All the faecal specimens were analysed with Hemoccult II slides and the 3,3',5,5'-tetramethylbenzidine (TMB) test 0.10%. For technical reasons, however, the Hemoccult test could not be evaluated. The TMB test showed faecal blood in 50 persons. A case history was obtained in 49 persons, of whom 47 agreed to further clinical, radiological, and endoscopic investigations. The most important findings in these examinations were resectable colonic carcinoma (Dukes's stage B) in 1 subject, a gastric ulcer in 1, haemorrhagic gastritis in 1, duodenal ulcers in 2, and colorectal polyps in 11 persons. The cost of the study was estimated to be NOK 114,000 (about USD 16,000).

Occult faecal blood loss determined by a 51Cr method and chemical tests in patients referred for upper gastrointestinal endoscopy.

In 119 patients referred for upper gastrointestinal endoscopy, the faecal blood loss was determined by a 51Cr method and 7 chemical tests. For patients with negative upper endoscopy (no. = 8), atrophic gastritis (no. = 30), gastric ulcer (no. = 31), or gastric cancer (no. = 23), the median 51Cr-determined faecal blood loss was 0.51, 0.61, 0.83, and 2.68 ml/24 h, respectively. For all chemical tests, the results were highly influenced by the upper time limit for positive reaction. Mixing of faecal specimens before testing did not prove essential. By repeated analyses of faecal samples stored for 3 days, the benzidine test showed a decreased sensitivity (p less than 0.01), whereas Fecatwin and Fecatwin sensitive showed an increased number of positive tests (p less than 0.01). Of cases of gastric cancer, tetramethylbenzidine tests including Hemo-Fec Test, benzidine test, Fecatwin sensitive, Hemoccult II, and Fecatwin could detect about 85%, 80%, 60%, 55%, and 30%, respectively.