The effect of a controlled gluten challenge in a group of patients with suspected non-coeliac gluten sensitivity: A randomized, double-blind placebo-controlled challenge.

BACKGROUND: Non-coeliac gluten-sensitivity (NCGS) has been proposed as a new entity with unknown prevalence and mechanisms, and there is a need for a standardized procedure to confirm the diagnosis. The objective of this study was to characterize the response to an oral gluten-challenge in patients with a symptom-relief when following a gluten free-diet (GFD). METHODS: Twenty patients (14F/6M, age range: 21-62 years) with suspected NCGS, without coeliac disease and wheat-allergy, were included while on a gluten-free diet. All patients went through four periods of double-blinded provocation, two with gluten and two with placebo in randomized order. They consumed two muffins a day (11/0 g gluten) for 4 days, followed by a 3-day wash-out. Gastrointestinal symptoms were recorded with questionnaires at baseline and after each provocation. We also investigated whether patients were able to correctly identify periods with gluten-exposure. KEY RESULTS: Collectively the whole group reported the most severe symptoms after placebo (P = .012). Four out of twenty patients correctly identified the two periods when they received gluten, hence were diagnosed with NCGS. The diagnosed-group tended to show higher symptom scores than the not-diagnosed group both at baseline, after gluten exposure and after placebo, but no clear difference was seen between provocation with gluten and placebo. The not-diagnosed group showed more severe symptoms with placebo than with gluten (P = .029). CONCLUSIONS AND INFERENCES: The present study showed that the majority of patients with suspected NCGS are not able to identify when challenged with gluten in a double-blind placebo-controlled food challenge, indicating that gluten is not the cause of their symptoms.

Sucralfate does not ameliorate acute radiation proctitis: randomised study and meta-analysis.

AIMS: During pelvic radiotherapy, many patients develop radiation-induced gastrointestinal symptoms, which may interfere with treatment. Prophylaxis during radiotherapy should ideally prevent acute reaction and the development of delayed injury. Sucralfate, an aluminium sucrose octasulphate, has been used for acute and delayed radiation side-effects. However, conflicting results have been published. We report here a prospective, randomised, placebo-controlled study of prophylactic sucralfate during pelvic radiotherapy. In addition, a meta-analysis of available data from the literature has been carried out. MATERIALS AND METHODS: Fifty-one patients with localised pelvic tumours scheduled for curative conformal pelvic radiotherapy (total dose 64-70 Gy over 6.5-7 weeks in 2 Gy daily fractions) were included. Peroral sucralfate 2 g three times daily, or identically appearing placebo tablets, was given during the course of radiotherapy. Symptom registration, endoscopy and biopsies were carried out immediately before radiotherapy, 2 weeks and 6 weeks into the treatment course, and 2 weeks after completing radiotherapy. Mucosal cup forceps biopsies were obtained through a rigid proctoscope. Graded endoscopic appearance and quantitative histology were registered. RESULTS: On the basis of previously published negative reports, an unplanned interim analysis of 44 evaluable patients showed significantly increased diarrhoea in the sucralfate group and the trial was stopped. No difference was seen in other symptoms, endoscopic appearance or histology. A meta-analysis comprising five published studies showed no statistically significant beneficial effect of sucralfate on acute symptoms. CONCLUSION: Sucralfate cannot be recommended for prophylaxis of acute radiation proctopathy and may even worsen the symptoms.

Faecal calprotectin and lactoferrin as markers of acute radiation proctitis: a pilot study of eight stool markers.

BACKGROUND: Non-invasive diagnostic tools to evaluate the severity of acute, radiation-induced proctitis are not readily available. The faecal excretion of eight markers of gut inflammation was therefore examined. Five proteins and three lipid derivates were analysed in sequential stool samples taken before and during radiation therapy. METHODS: Stool samples from 15 patients with prostate cancer scheduled for radiation therapy were examined. Pretreatment and in-treatment samples (2nd and 6th weeks) were measured by enzyme-linked immunosorbent assay (ELISA) (calprotectin, lactoferrin, transferrin, leukotriene B4, prostaglandin E2, thromboxane B2 and TNF alpha) or nephelometry (alpha 1-antitrypsin). RESULTS: Calprotectin and lactoferrin concentrations increased significantly during radiation treatment (P = 0.0005 and P = 0.019). Transferrin was detected in only 9 out of 45 samples. There were no changes in tumour necrosis factor alpha (TNF alpha), leukotriene B4, prostaglandin E2 and thromboxane B2 during treatment. alpha 1-antitrypsin could not be detected in any sample. CONCLUSIONS: This study indicates that faecal calprotectin and lactoferrin concentrations could be markers of acute, radiation-induced proctitis. Patient compliance and stability of the markers make this a promising method for clinical research. Eicosanoids could be measured in stool samples, but the concentrations did not increase with increasing radiation dose.

High frequency of coeliac disease among patients with autoimmune adrenocortical failure.

BACKGROUND: Coeliac disease (CD) is an autoimmune disease of the small intestine caused by gluten ingestion in genetically predisposed subjects. It can occur isolated or in combination with other autoimmune diseases. Autoimmune Addison's disease is frequently associated with other organ-specific autoimmune diseases. We have investigated the prevalence of CD among a large cohort of patients with autoimmune Addison's disease. METHODS: Seventy-six patients (44 women) with Addison's disease, 52% of whom had polyendocrine failure, were recruited from a registry of organ-specific autoimmune diseases in Norway. All sera were analysed for antibodies against gliadin (AGA), endomysium (EMA) and tissue transglutaminase (tTG). Patients with positive EMA and/or anti-tTG were offered endoscopy. The human leucocyte antigen (HLA) class II genotypes were determined. RESULTS: Five patients had antibodies against both endomysium and tissue transglutaminase. In these five patients, CD was verified by biopsy. One patient had known CD prior to the study. All six patients with CD carried the CD-associated HLA haplotype DR3-DQ2. The total prevalence of CD was 7.9%. CONCLUSION: CD is frequently associated with Addison's disease. The risk of developing CD seems to be higher than can be explained by the common DR3-DQ2 association alone. It is often asymptomatic or associated with unspecific symptoms. Addison patients should be screened for the presence of CD on a regular basis.

Acute radiation proctitis: a sequential clinicopathologic study during pelvic radiotherapy.

PURPOSE: Rectal toxicity is often dose limiting during pelvic radiation therapy. This prospective study examined the sequential development and associations of clinical, endoscopic, and histopathologic rectal toxicity during ongoing radiation therapy. METHODS AND MATERIALS: Thirty-three patients with nongastrointestinal pelvic carcinomas underwent proctoscopy with biopsy before radiation therapy, after 2 weeks treatment, and toward the end of the treatment course (6 weeks). Symptoms of acute toxicity were recorded, and endoscopic changes were graded. Histologic changes in the surface epithelium, glandular layer, and lamina propria were assessed using an ad hoc scoring system. Macrophage accumulation was evaluated in anti-CD68 stained sections. RESULTS: Pretreatment endoscopy and biopsies were unremarkable. Clinical symptoms progressed toward the end of the treatment course. In contrast, endoscopic pathology was maximal at 2 weeks. Biopsies obtained during treatment exhibited atrophy of the surface epithelium, acute cryptitis, crypt abscesses, crypt distortion and atrophy, and stromal inflammation. Histologic changes, particularly those in the surface epithelium, were consistently more pronounced at 2 weeks than they were at 6 weeks. CONCLUSION: In contrast to clinical symptoms, endoscopic changes stabilize and histologic changes regress from the 2nd to the 6th week of treatment. These results may have implications for the design and timing of prophylactic and therapeutic interventions to reduce radiation proctitis.

[Neurological diseases associated with celiac disease]. / Nevrologisk sykdom assosiert med cøliaki.

During the period from May 1997 to October 1998, eight patients with coeliac disease or dermatitis herpetiformis and neurological disorders were admitted to the Department of Neurology, University Hospital of Bergen. The most frequent conditions were polyneuropathy (seven patients) and spinocerebellar ataxia (three patients). Other conditions were lower motor neuron disease, myelopathy, epilepsy and encephalopathy. The patients used various degrees of gluten-free diet at the time of admission. It remains unclear whether there is a shared common pathogenetic mechanism or the neurological disorder is a complication to the coeliac disease. Both vitamin depletion and immunological mechanisms may cause neurological disorder. Neurological manifestations may occur before the gastrointestinal symptoms. With reference to our patients and available literature we discuss prevalence, clinical picture, pathogenesis, treatment and prognosis. Neurologists, gastroenterologists and general practitioners should be aware that coeliac disease can cause neurological diseases, especially polyneuropathy, cerebellar ataxia and encephalopathy.

[Screening for celiac disease in adults]. / Screening for cøliaki hos voksne.

This article is a review of literature from Medline and other sources, which shows that coeliac disease is far more prevalent than previously considered. The clinical picture is very diverse, making diagnosis difficult in many patients and calling for great clinical awareness. Even patients with no or few symptoms have biochemical signs of malabsorption, e.g. folate, vitamin, and iron deficiency, and many exhibit osteopenia. Patients with untreated coeliac disease carry a significant risk of developing malignancies. Risk groups for screening are family members, patients with coeliac associated disorders, and patients with uncharacteristic symptoms. Screening among apparently healthy subjects has been carried out for epidemiological purposes, but is not recommended outside protocols. Diagnosing coeliac disease is important because lifelong strict dietary treatment is effective in alleviating symptoms and preventing longterm complications.

[Screening for adult celiac disease]. / Screening for cøliaki hos voksne.

This article is a review of literature from Medline and other sources, which shows that coeliac disease is far more prevalent than previously considered. The clinical picture is very diverse, making diagnosis difficult in many patients and calling for great clinical awareness. Even patients with no or few symptoms have biochemical signs of malabsorption, e.g. folate, vitamin, and iron deficiency, and many exhibit osteopenia. Patients with untreated coeliac disease carry a significant risk of developing malignancies. Risk groups for screening are family members, patients with coeliac associated disorders, and patients with uncharacteristic symptoms. Screening among apparently healthy subjects has been carried out for epidemiological purposes, but is not recommended outside protocols. Diagnosing coeliac disease is important because lifelong strict dietary treatment is effective in alleviating symptoms and preventing longterm complications.

High prevalence of asymptomatic coeliac disease in Norway: a study of blood donors.

OBJECTIVE: The prevalence of symptomatic coeliac disease in Norway is 1:675. Coeliac disease has previously been reported in presumably healthy people. Our aim was to determine the prevalence of latent coeliac disease in apparently healthy (i.e. asymptomatic) Norwegian individuals. METHODS: Blood donor sera were tested for gluten antibodies (IgA, IgG). Positive samples (IgA AGA > 0.35, IgG AGA > 0.90) were further tested for endomysium antibodies (IgA EMA). EMA positive individuals were offered gastroenterological investigation. RESULTS: Of 2096 sera, 83 fulfilled the criteria for EMA testing (M/F = 55/28). Eight individuals were EMA positive. On biopsy, seven out of eight had villous atrophy (six subtotal, one partial). None of the patients had significant symptoms. Biochemical data showed iron deficiency (two), hypocalcaemia (one), and low serum zinc (five). All patients were treated with a gluten-free diet and followed up. CONCLUSION: The study indicates a prevalence of 1:340 among asymptomatic and presumably healthy people. This is in keeping with studies from other countries. Lack of symptoms does not exclude secondary deficiency conditions.

[Inflammatory bowel disease and pregnancy]. / Inflammatorisk tarmsykdom og graviditet.

Inflammatory bowel disease (ulcerative colitis and Crohn's disease) is a chronic illness, often affecting people of reproductive age. Treatment involves drugs which have potential side effects and because of this pregnancy causes considerable concern. The course of the disease is not much affected by pregnancy. The relapse rate is only slightly increased when the disease is active at the time of conception. Relapses during pregnancy should be treated in the usual manner. Surgical intervention should be carried out on the same indications as in those who are not pregnant. Frequency of complications is not increased during pregnancy, at delivery or post partum. Sectio may be necessary in perianal disease. With few exceptions, drug treatment should be continued throughout pregnancy. No adverse effects are seen with normal doses of sulfasalazine, 5-amino-salicylic acid and steroids. Planned pregnancies should be started in periods of quiescent disease.

The symptomatic effect of cisapride in patients with irritable bowel syndrome and constipation.

BACKGROUND: Cisapride improves symptoms in patients with idiopathic constipation. This trial compares the effect of cisapride with that of placebo in patients with irritable bowel syndrome (IBS) and constipation. METHODS: Seventy patients were randomized to 12 weeks' treatment with 5 mg cisapride three times daily or placebo in a double-blind trial. The dose could be doubled after 4 weeks in patients without satisfactory improvement. The patients scored their symptoms on a 100-mm visual analogue scale (VAS) (0 = best, 100 = worst), and the investigators evaluated the symptomatic effect. RESULTS: The dose was doubled in 17 and 23 patients in the cisapride and placebo groups, respectively, after 4 weeks. The patients' mean VAS score for global evaluation of IBS symptoms in the cisapride and placebo groups was 73 and 71 mm, respectively, at the start of treatment and 47 and 41 mm at the end. The difference between cisapride and placebo at the end was 6 mm in favour of placebo (95% confidence interval (CI), -6, 18) (NS). The investigators evaluated the effect as good or excellent in 39.2% and 58.8% in the cisapride and placebo groups, respectively. The difference in favour of placebo was 19.5% (95% CI, -5, 44) (NS). Nor were any statistically significant differences seen between cisapride and placebo in the other effect factors. CONCLUSIONS: The trial seems to exclude a clinically significant effect of 15-30 mg cisapride daily in patients with IBS and constipation during a 12-week treatment period.

[Celiac disease in the elderly]. / Cøliaki hos eldre.

Coeliac disease appears at all ages and increasing prevalence in advanced age has been reported. We registered and followed up all coeliac patients during an 11 year period. The article describes the occurrence in elderly persons. Data were collected on symptomatology, laboratory test results, complications, dietary treatment, and progress. A total of 69 coeliacs were registered, giving a crude prevalence of 148/100,000. 13 patients (19%) were 65 years old or older at the time of diagnosis. Mean estimated diagnostic delay in this group was 21.5 years (range 5-40). The symptomatology was uncharacteristic in most patients and not dominated by malabsorption symptoms. Laboratory investigations were generally unhelpful for diagnosis. There was a high frequency of associated disorders, notably malignant diseases. Histology is a sine qua non in the diagnosis of coeliac disease, especially in elderly patients. Wide indications for biopsy are strongly recommended in this age group.

[Gastrointestinal diseases--the place of endoscopy in examination, treatment and control]. / Gastrointestinale sykdommer--endoskopiens plass i utredning, behandling og kontroll.

Dyspepsia, defined as discomfort in the upper abdomen after a meal, is the most frequent indication for gastroscopy. Such dyspepsia was earlier considered to be an element of the ulcer disease, Moynihan's disease. Whether examination showed an ulcer or not was of minor importance as long as the treatment was the same. Similar opinions still contribute to a negative attitude towards the need to obtain a more specific diagnosis, especially in young patients where risk of cancer is low. We are of the opinion that dyspepsia is a non-specific symptom of several different diseases, and that curative therapy is often available today provided the diagnosis is correct. It is therefore necessary to make an active effort to diagnose the cause of the dyspepsia, also in younger persons. In practice, this means that there are many different indications for gastroscopy. We try, however, to practice a restrictive policy with respect to control gastroscopy.

Lansoprazole versus omeprazole in short-term treatment of reflux oesophagitis. Results of a Scandinavian multicentre trial.

To evaluate the therapeutic potential of the newly developed proton pump inhibitor lansoprazole in patients with reflux oesophagitis, we performed a double-blind randomized clinical trial comparing 20 mg omeprazole and 30 mg lansoprazole, involving 229 patients at 9 Scandinavian hospitals. The treatment period was 4 or 8 weeks, and main efficacy variables were healing of endoscopic changes, relief of reflux symptoms, and occurrence of adverse events. No significant difference in terms of healing was found, either after 4 or after 8 weeks' treatment. Patients receiving lansoprazole experienced a greater improvement in heartburn after 4 weeks (p = 0.03), and there was a similar trend for acid regurgitation. Lansoprazole was found to be an effective and safe alternative to omeprazole in short-term treatment of moderate reflux oesophagitis.

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.

Loperamide treatment of the irritable bowel syndrome.

The effect of loperamide was investigated in a double-blind, placebo-controlled study in 60 patients with irritable bowel syndrome (IBS). Active treatment was given in low dosage (4 mg nocte). The effect of treatment was assessed in clinical subgroups. In a group of patients with painless diarrhoea (n = 16) there was a highly significant improvement in stool frequency and consistency. In a group with alternating bowel habits and abdominal pain (n = 21) there was also a statistically significant improvement in stool frequency and consistency as well as significantly fewer painful days during loperamide treatment. Patients with alternating bowel habits and no pain (n = 12) experienced no symptomatic improvement, and patients with constipation (n = 9) generally felt worse on loperamide. No side effects were encountered. It is concluded that loperamide can be considered an alternative symptomatic treatment in some IBS patients whose main symptoms are painless diarrhoea or alternating bowel habits associated with abdominal pain.