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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. [ABSTRACT FROM AUTHOR]

Intestinal absorption and bacteriology of the ileal contents were compared in seven patients with continent ileostomy and seven patients with conventional ileostomy. The absorption of vitamin B12 was reduced in five patients with continent ileostomy and subnormal in two patients with conventional ileostomy. Steatorrhoea was present in four patients with continent and one patient with conventional ileostomy. Increased concentrations of total anaerobic bacteria and Bacteroides were found in the ileum of the patients with continent ileostomy. After an oral dose of (1-14C) glycocholic acid there was no difference in the faecal excretion of radioactivity, whereas the 14CO2-expiration was increased in two patients with continent ileostomy. In four patients with continent ileostomy and malabsorption of B12, there was evidence of a stagnant loopsyndrome as oral lincomycin treatment resulted in increased absorption of B12 decreased excretion of faecal fat, and decreased concentrations of Bacteroides in the ileum. [ABSTRACT FROM PUBLISHER]

Objective: Activating mutations in the GUCY2C gene, which encodes the epithelial receptor guanylate cyclase C, cause diarrhea due to increased loss of sodium chloride to the intestinal lumen. Patients with familial GUCY2C diarrhea syndrome (FGDS) are predisposed to inflammatory bowel disease (IBD). We investigated whether genes in the guanylate cyclase C pathway are enriched for association with IBD and reversely whether genetic or transcriptional changes associated with IBD are found in FGDS patients., Methods: (1) A set of 27 genes from the guanylate cyclase C pathway was tested for enrichment of association with IBD by Gene Set Enrichment Analysis, using genome-wide association summary statistics from 12,882 IBD patients and 21,770 controls. (2) We genotyped 163 known IBD risk loci and sequenced NOD2 in 22 patients with FGDS. Eight of them had concomitant Crohn's disease. (3) Global gene expression analysis was performed in ileal tissue from patients with FGDS, Crohn's disease and healthy individuals., Results: The guanylate cyclase C gene set showed a significant enrichment of association in IBD genome-wide association data. Risk variants in NOD2 were found in 7/8 FGDS patients with concomitant Crohn's disease and in 2/14 FDGS patients without Crohn's disease. In ileal tissue, downregulation of metallothioneins characterized FGDS patients compared to healthy controls., Conclusions: Our results support a role of guanylate cyclase C signaling and disturbed electrolyte homeostasis in development of IBD. Furthermore, downregulation of metallothioneins in the ileal mucosa of FGDS patients may contribute to IBD development, possibly alongside effects from NOD2 risk variants.

Rationale: Patients with radiation-induced enteropathy (RE) after cancer treatment show similar symptoms as patients with irritable bowel syndrome (IBS). The low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet (LFD) is a widespread management strategy for IBS. We aimed to investigate if there may be a positive effect of LFD on symptoms and health-related quality of life (HRQOL) in patients with RE., Methods: In an open non-controlled pilot study, 11 patients (all female) with RE-related IBS symptoms were recruited largely based on own initiative. All followed LFD for four weeks. IBS Severity Scoring System (IBS-SSS) and IBS Symptom Questionnaire (IBS-SQ) were used to assess symptoms. Short Form Nepean Dyspepsia Index (SF-NDI) and 12-item Short Form Health Survey (SF-12) evaluated HRQOL. A three day food record was used to estimate baseline intake of FODMAPs and to reveal dietary changes., Results: FODMAP intake was successfully reduced, although LFD was found a burdensome intervention. IBS symptoms improved significantly based on mean total score of IBS-SSS and IBS-SQ, which changed from 310.2 ± 60.7 to 171.4 ± 107.2 (p = .001) and 27.4 ± 4.1 to 15.7 ± 10.1 (p = .002). HRQOL improved based on SF-NDI total score (30.5 ± 9.4 to 18.3 ± 8.2, p = .001) and based on mental (p = .047) and physical (p = .134) score of SF-12. Main additional dietary changes were reduced intake of energy, carbohydrates, and fiber., Conclusion: Our findings from this small-scaled pilot study indicate that the LFD may alleviate symptoms and improve HRQOL in patients with RE. Further controlled studies with larger sample size should be conducted to verify our results and hopefully enable implementation of LFD as a future part of the management strategy for RE.

Objective: Familial GUCY2C diarrhoea syndrome (FGDS) is caused by an activating mutation in the GUCY2C gene encoding the receptor guanylate cyclase C in enterocytes. Activation leads to increased secretion of fluid into the intestinal lumen. Twenty percent of the patients have increased risk of Crohn's disease and intestinal obstruction (CD, 20%) and the condition resembles irritable bowel syndrome with diarrhoea. We aimed to describe fluid content, contractility, peristaltic activity and bowel wall thickness in the intestine in fasting FGDS patients, using ultrasound, with healthy volunteers serving as controls., Methods: Twenty-three patients with FGDS and 22 healthy controls (HC) were examined with a Logiq E9 scanner in a fasting state. Bowel wall thickness was measured and fluid-filled small bowel loops were counted using three-dimensional (3D) magnetic positioning navigation. The HC ingested 500 ml PEG solution, an electrolyte balanced, non-absorbable solution, in order to investigate the contractions of the small bowel., Results: The fasting 23 FGDS patients had significantly higher number of fluid-filled small bowel segments compared to 22 fasting HC, p < 0.001. A high number of non-occlusive contractions in the ileum was observed, which was significant when compared to HC after ingesting PEG solution, p < 0.016. An increase in intestinal wall thickness or other signs of CD were not observed., Conclusions: FGDS is characterised by multiple, fluid-filled small bowel loops with incomplete contractions and fluid stagnation in fasting state. These findings may play a role in the increased risk of bowel obstruction as well as IBS-like symptoms observed in these patients.

Epigenetic and microbiome changes during pediatric development have been implicated as important elements in the developmental origins of inflammatory bowel diseases (IBDs) including Crohn's disease (CD) and ulcerative colitis (UC), which are linked to early onset colorectal cancer (CRC). Colonic mucosal samples from 22 control children between 3.5 and 17.5 years of age were studied by Infinium HumanMethylation450 BeadChips and, in 10 cases, by 454 pyrosequencing of the bacterial 16S rRNA gene. Intercalating age-specific DNA methylation and microbiome changes were identified, which may have significant translational relevance in the developmental origins of IBD and CRC.

The literature was searched for publications on minerals and vitamins during pregnancy and the possible influence of supplements on pregnancy outcome. Maternal iron (Fe) deficiency has a direct impact on neonatal Fe stores and birth weight, and may cause cognitive and behavioural problems in childhood. Fe supplementation is recommended to low-income pregnant women, to pregnant women in developing countries, and in documented deficiency, but overtreatment should be avoided. Calcium (Ca) deficiency is associated with pre-eclampsia and intra-uterine growth restriction. Supplementation may reduce both the risk of low birth weight and the severity of pre-eclampsia. Gestational magnesium (Mg) deficiency may cause hematological and teratogenic damage. A Cochrane review showed a significant low birth weight risk reduction in Mg supplemented individuals. Intake of cereal-based diets rich in phytate, high intakes of supplemental Fe, or any gastrointestinal disease, may interfere with zinc (Zn) absorption. Zn deficiency in pregnant animals may limit fetal growth. Supplemental Zn may be prudent for women with poor gastrointestinal function, and in Zn deficient women, increasing birth weight and head circumference, but no evidence was found for beneficial effects of general Zn supplementation during pregnancy. Selenium (Se) is an antioxidant supporting humoral and cell-mediated immunity. Low Se status is associated with recurrent abortion, pre-eclampsia and IUGR, and although beneficial effects are suggested there is no evidence-based recommendation for supplementation. An average of 20-30% of pregnant women suffer from any vitamin deficiency, and without prophylaxis, about 75% of these would show a deficit of at least one vitamin. Vitamin B6 deficiency is associated with pre-eclampsia, gestational carbohydrate intolerance, hyperemesis gravidarum, and neurologic disease of infants. About 25% of pregnant women in India are folate deficient. Folate deficiency may lead to congenital malformations (neural tube damage, orofacial clefts, cardiac anomalies), anaemia and spontaneous abortions, and pre-eclampsia, IUGR and abruption placentae. Pregestational supplementation of folate prevents neural tube defects. A daily supplemental dose of 400 μg/day of folate is recommended when planning pregnancy. In developing countries diets are generally low in animal products and consequently in vitamin B12 content. An insufficient supply may cause reduced fetal growth. In vegetarian women, supplementation of vitamin B12 may be needed. Vitamin A deficiency is prevalent in the developing world, impairing Fe status and resistance to infections. The recommended upper limit for retinol supplements is 3000 IU/day. Vitamin A supplementation enhances birth weight and growth in infants born to HIV-infected women. Overdosing should be avoided. Low concentrations of vitamin C seem to increase the development of pre-eclampsia, and supplementation may be beneficial. Supplementation with vitamin D in the third trimester in vitamin D deficient women seems to be beneficial. The use of vitamins E, although generally considered "healthy", may be harmful to the pregnancy outcome by disrupting a physiologic oxidative gestational state and is consequently not recommended to prevent pre-eclampsia. Further studies on specific substances are needed as the basis for stratified, placebo-controlled analyses., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Familial diarrhea disorders are, in most cases, severe and caused by recessive mutations. We describe the cause of a novel dominant disease in 32 members of a Norwegian family. The affected members have chronic diarrhea that is of early onset, is relatively mild, and is associated with increased susceptibility to inflammatory bowel disease, small-bowel obstruction, and esophagitis., Methods: We used linkage analysis, based on arrays with single-nucleotide polymorphisms, to identify a candidate region on chromosome 12 and then sequenced GUCY2C, encoding guanylate cyclase C (GC-C), an intestinal receptor for bacterial heat-stable enterotoxins. We performed exome sequencing of the entire candidate region from three affected family members, to exclude the possibility that mutations in genes other than GUCY2C could cause or contribute to susceptibility to the disease. We carried out functional studies of mutant GC-C using HEK293T cells., Results: We identified a heterozygous missense mutation (c.2519G→T) in GUCY2C in all affected family members and observed no other rare variants in the exons of genes in the candidate region. Exposure of the mutant receptor to its ligands resulted in markedly increased production of cyclic guanosine monophosphate (cGMP). This may cause hyperactivation of the cystic fibrosis transmembrane regulator (CFTR), leading to increased chloride and water secretion from the enterocytes, and may thus explain the chronic diarrhea in the affected family members., Conclusions: Increased GC-C signaling disturbs normal bowel function and appears to have a proinflammatory effect, either through increased chloride secretion or additional effects of elevated cellular cGMP. Further investigation of the relevance of genetic variants affecting the GC-C-CFTR pathway to conditions such as Crohn's disease is warranted. (Funded by Helse Vest [Western Norway Regional Health Authority] and the Department of Science and Technology, Government of India.).

Acute radiation proctitis was evaluated before, during and after radiotherapy (RT) for prostate cancer. The main aims of the study were to examine changes related to the increasing radiation dose, and identify surrogate markers of gastrointestinal (GI) reaction to radiation. Twenty consecutive prostate cancer patients scheduled for 7 weeks of conformal RT were prospectively included in a longitudinal study assessing symptoms, inflammation in rectal mucosa biopsies, and blood and stool samples at four time points (before RT and 2, 6 and 11 weeks after start of RT). Blood samples were examined for acute phase response-related markers, fatty acids (FAs), vitamin E and leukotriene B(4) (LTB(4)). Lactoferrin, calprotectin and S100A12 were measured in stool samples and FAs in biopsies from rectal mucosa. The increase in histopathological inflammation reached a maximum 2 weeks after start of RT. Symptoms of GI toxicity increased with higher radiation dose and had not returned to pre-treatment level 4 weeks after RT. Lactoferrin concentrations in stool increased significantly at week 6. Significant decreases of vitamin E, leukocyte count, hemoglobin and some groups of FAs were discovered, while a few FAs increased significantly during the study period. Time courses vary between the selected indicators of acute radiation proctitis. The biopsy grading of inflammatory changes were most intense 2 weeks into the treatment period while symptoms continued to increase until week 6. Lactoferrin in stool samples could be a non-invasive marker of GI inflammation during RT. A transient decrease in vitamin E and some FAs during RT warrants further studies.

Purpose: Rectal toxicity (proctitis) is a dose-limiting factor in pelvic radiation therapy. Mucosal atrophy, i.e., net extracellular matrix degradation, is a prominent feature of radiation proctitis, but the underlying mechanisms are not known. We prospectively examined changes in matrix metalloproteinase (MMP)-2 and MMP-9 (gelatinase A and B) in the rectal mucosa during radiation therapy of prostate cancer, as well as the relationships of these changes with symptomatic, structural, and cellular evidence of radiation proctitis., Methods and Materials: Seventeen patients scheduled for external beam radiation therapy for prostate cancer were prospectively enrolled. Symptoms of gastrointestinal toxicity were recorded, and endoscopy with biopsy of the rectal mucosa was performed before radiation therapy, as well as 2 and 6 weeks into the treatment course. Radiation proctitis was assessed by endoscopic scoring, quantitative histology, and quantitative immunohistochemistry. MMP-2 and MMP-9 were localized immunohistochemically, and activities were determined by gelatin zymography., Results: Symptoms, endoscopic scores, histologic injury, and mucosal macrophages and neutrophils increased from baseline to 2 weeks. Symptoms increased further from 2 weeks to 6 weeks, whereas endoscopic and cellular evidence of proctitis did not. Compared to pretreatment values, there was increased total gelatinolytic activity of MMP-2 and MMP-9 at 2 weeks (p = 0.02 and p = 0.004, respectively) and 6 weeks (p = 0.006 and p = 0.001, respectively). Active MMP-2 was increased at both time points (p = 0.0001 and p = 0.002). Increased MMP-9 and MMP-2 at 6 weeks was associated with radiation-induced diarrhea (p = 0.007 and p = 0.02, respectively) and with mucosal neutrophil infiltration (rho = 0.62)., Conclusions: Pelvic radiation therapy causes increased MMP-2 and MMP-9 activity in the rectal mucosa. These changes correlate with radiation-induced diarrhea and granulocyte infiltration and may contribute to abnormal connective tissue remodeling in radiation proctitis.

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.

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.

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.

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.

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.

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.

Sixty patients with endoscopically confirmed duodenal ulcers were treated with 50 mg of trimipramine daily. After the end of the treatment 45 patients showed healed ulcers. Ulcer healing was not related to serum concentration of trimipramine, but seemed to be influenced by smoking habits and duration of the total and actual disease history.

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.

Sixty-two patients with healed duodenal or prepyloric ulcers completed a double-blind long-term trial with either 25 mg/day of trimipramine (32 patients) or placebo (30 patients). Endoscopy was performed when marked dyspeptic complaints occurred or after a 1-year follow-up study. Eleven patients in the trimipramine-treated group and 18 patients in the placebo group had relapses, with endoscopically confirmed ulcers or erosions with duodenitis and severe symptoms, revealing a statistically significant difference between the groups in favour of trimipramine. Twenty-one patients (66%) receiving trimipramine and 12 patients (40%) receiving placebo were in remission at the end of the study. The probability of having a relapse increased with the time from start of placebo but decreased in the group that received trimipramine. No serious side effects occurred. In conclusion, 25 mg of trimipramine daily reduced significantly the recurrence rate of duodenal ulcer disease, when compared with placebo.

A 1-year material of 75 ERCP investigations is reported from a small community hospital serving an area of 40,000 inhabitants. A cannulation success rate of 90.7% was found. No complications were seen. The use of the procedure in a small hospital is discussed.

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.