A sustained hypothalamic-pituitary-adrenal axis response to acute psychosocial stress in irritable bowel syndrome.

BACKGROUND: Despite stress being considered a key factor in the pathophysiology of the functional gastrointestinal (GI) disorder irritable bowel syndrome (IBS), there is a paucity of information regarding the ability of IBS patients to respond to acute experimental stress. Insights into the stress response in IBS could open the way to novel therapeutic interventions. To this end, we assessed the response of a range of physiological and psychological parameters to the Trier Social Stress Test (TSST) in IBS. METHOD: Thirteen female patients with IBS and 15 healthy female age-matched control participants underwent a single exposure to the TSST. Salivary cortisol, salivary C-reactive protein (CRP), skin conductance level (SCL), GI symptoms, mood and self-reported stress were measured pre- and post-exposure to the TSST. RESULTS: The hypothalamic-pituitary-adrenal (HPA) axis response to the TSST was sustained in IBS, as shown by a greater total cortisol output throughout (p = 0.035) and higher cortisol levels measured by an area under the curve with respect to ground (AUCG) analysis (p = 0.044). In IBS patients, GI symptoms increased significantly during the recovery period following exposure to the TSST (p = 0.045). Salivary CRP and SCL activity showed significant changes in relation to stress but with no differential effect between experimental groups. CONCLUSIONS: Patients with IBS exhibit sustained HPA axis activity, and an increase in problematic GI symptoms in response to acute experimental psychosocial stress. These data pave the way for future interventional studies aimed at identifying novel therapeutic approaches to modulate the HPA axis and GI symptom response to acute psychosocial stress in IBS.

Cognitive performance in irritable bowel syndrome: evidence of a stress-related impairment in visuospatial memory.

BACKGROUND: Central nervous system (CNS) dysfunction is a prominent feature of the functional gastrointestinal (GI) disorder, irritable bowel syndrome (IBS). However, the neurobiological and cognitive consequences of key pathophysiological features of IBS, such as stress-induced changes in hypothalamic-pituitary-adrenal (HPA)-axis functioning, is unknown. Our aim was to determine whether IBS is associated with cognitive impairment, independently of psychiatric co-morbidity, and whether cognitive performance is related to HPA-axis function. METHOD: A cross-sectional sample of 39 patients with IBS, a disease control group of 18 patients with Crohn's disease (CD) in clinical remission and 40 healthy age- and IQ-matched control participants were assessed using the Paired Associates Learning (PAL), Intra-Extra Dimensional Set Shift (IED) and Spatial Working Memory (SWM) tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and a computerized Stroop test. HPA-axis function was determined by measuring the cortisol awakening response (CAR). RESULTS: IBS patients exhibited a subtle visuospatial memory deficit at the PAL six- pattern stage (p = 0.03), which remained after psychiatric co-morbidity was controlled for (p = 0.04). Morning cortisol levels were lower in IBS (p = 0.04) and significantly associated with visuospatial memory performance within IBS only (p = 0.02). CONCLUSIONS: For the first time, altered cognitive function on a hippocampal-mediated test of visuospatial memory, which was related to cortisol levels and independent of psychiatric co-morbidity, has been identified in IBS. Visuospatial memory impairment may be a common, but currently neglected, component of IBS. Further elucidation of the nature of this impairment may lead to a greater understanding of the underlying pathophysiology of IBS, and may provide novel therapeutic approaches.

A dietary survey of patients with irritable bowel syndrome.

BACKGROUND: Food is one of the most commonly reported triggers of irritable bowel syndrome (IBS) symptoms. However, the role of diet in the aetiology and management of IBS has not been clearly established. The present study aimed to examine the dietary practices of Irish patients with IBS and to determine whether these practices increased their vulnerability to nutritional inadequacies. METHODS: A questionnaire was completed by 135 IBS patients on their perceptions of the role of diet in their symptoms and whether they restrict their diet according to the symptoms experienced. A similar questionnaire was used to investigate the perceptions of 111 healthy subjects to the gastrointestinal symptoms experienced on the consumption of food. RESULTS: Food was considered to cause or worsen their gastrointestinal symptoms in 89.6% of IBS patients compared to 55% of healthy subjects (P < 0.001). Cereal-based foods, predominantly bread or its components, were the most frequently cited (53.3%), and spicy foods (39.3%), vegetables and fatty foods (35.6% for both) also featured prominently. A significantly greater number of patients with IBS reported changing their diet to minimise symptoms compared to healthy controls (91.9% versus 45.5%, P < 0.001). In relation to whole food groups, milk products (9.6%), fruit (7.4%) and vegetables (5.2%) were those most commonly restricted, with only a small number of IBS patients seeking professional healthcare advice. CONCLUSIONS: The majority of IBS patients consider their symptoms to be related to food, and change their diet by limiting the foods that they perceive as problematic, with some restricting whole food groups. Few patients sought professional healthcare advice when implementing dietary change, possibly exposing a considerable number to an increased risk of nutritional deficiency.

Plain abdominal radiographs in patients with Crohn's disease: radiological findings and diagnostic value.

AIM: To determine the diagnostic yield and clinical value of plain film of the abdomen (PFA) in Crohn's disease (CD) patients and to determine whether performance of PFA yields definitive diagnostic information or whether additional imaging examinations are required. MATERIALS AND METHODS: One hundred and seventy-seven CD patients underwent 643 PFAs during the period September 1992 to August 2008. Two radiologists blinded to the clinical details independently evaluated individual PFAs and/or their reports for abnormal findings using the following criteria: normal, small bowel (SB) findings; colonic findings, acute CD complications, extra-colonic findings; global assessment/impression. The results of additional imaging studies performed within 5 days of PFA were recorded and findings were analysed. RESULTS: A mean of 3.6 (range 1-22) PFAs was performed per patient during the study period. Almost 70% of films were normal (n = 449). SB abnormalities were detected in 21.8% (n = 140) PFAs; most commonly dilated loops (18.8%, n = 121) and mucosal oedema (5%, n = 32). Colonic abnormalities were present in 11.4% (n = 73); most commonly mucosal oedema (7.5%, n = 48) and dilated loops (5%, n = 32). Four cases of pneumoperitoneum were detected. There was no case of toxic megacolon. There was one case in which intra-abdominal abscess/collection was suspected and two cases of obstruction/ileus. Extracolonic findings (renal calculi, sacro-iliitis, etc.) were identified in 7.5% (n = 48). PFAs were followed by additional abdominal imaging within 5 days of PFA in 273/643 (42.5%) of cases. CONCLUSION: Despite the high rates of utilization of PFA in CD patients, there is a low incidence of abnormal findings (32.5%). Many of the findings are non-specific and clinically irrelevant and PFA is frequently followed by additional abdominal imaging examinations.

Low levels of adherence with proton pump inhibitor therapy contribute to therapeutic failure in gastroesophageal reflux disease.

To assess adherence to proton pump inhibitor (PPI) treatment and associated variables in patients with gastroesophageal reflux disease (GERD). Cross-sectional and prospective comprising 240 consecutive adult patients, diagnosed with GERD for whom continuous use of standard or double dose of omeprazole had been prescribed. Patients were ranked as ne-GERD (162: 67.5%) or e-GERD classified according to the Los Angeles classification as A (48:20.0%), B (21:8.6%), C (1:0.5%), D (1:0.5%), and Barrett's esophagus (7:2.9%). The Morisky questionnaire was applied to assess adherence to therapy and a GERD questionnaire to assess symptoms and their impact. Adherence was correlated with demographics, cotherapies, comorbidities, treatment duration, symptoms scores, endoscopic findings, and patient awareness of their disease. 126 patients (52.5%) exhibited high level of adherence and 114 (47.5%) low level. Youngers (P= 0.002) or married (O.R. 2.41, P= 0.03 vs. widowers) patients had lower levels of adherence; symptomatic patients exhibited lower adherence (P= 0.02). All other variables studied had no influence on adherence. Patients with GERD attending a tertiary referral hospital in São Paulo exhibited a high rate of low adherence to the prescribed PPI therapy that may play a role in the therapy failure. Age <60 years, marital status and being symptomatic were risk factors for low adherence.

Fecal bacterial microbiota in constipated patients before and after eight weeks of daily Bifidobacterium infantis 35624 administration.

INTRODUCTION AND AIM: In recent years, probiotics have been used in functional gastrointestinal disorders, including chronic constipation (CC). The effect of Bifidobacterium infantis strain 35624 on the gut microbiota of CC patients has not been previously studied. Our aim was to analyze the fecal microbiota of constipated patients, before and after consuming a single-strain probiotic (B. infantis strain 35624). MATERIALS AND METHODS: We used 16S rRNA gene high-throughput sequencing to analyze the fecal microbiota of female patients (n=13) with CC. Patients were instructed to ingest one capsule of Alflorex® (containing 1×109 CFUs/g B. infantis strain 35624) daily for eight weeks. Fecal samples were obtained at the baseline and end (final) of probiotic administration. RESULTS: Alpha diversity metrics did not differ between the baseline and final periods. The butyrate producer, Oscillospira, was the taxon most strongly correlated with amplicon sequence variants (R2=0.55, p<0.0001). Except for a few bacterial taxa, there were no significant differences in relative abundance between the baseline and final periods. Beta-diversity measures also showed limited evidence for the differences between the two time periods. CONCLUSIONS: The results suggest that the fecal bacterial microbiota remains stable in constipated women consuming a single-strain probiotic. Those findings may be helpful in better understanding probiotic functioning in patients with digestive disorders.

Gastric pacing for diabetic gastroparesis--does it work?

The management of diabetic gastroparesis resistant to medical therapy is very difficult Gastric electrical stimulation (GES) is a relatively new therapeutic modality which has shown some promise in international trials. It has seen use in four patients in Ireland. Our aim was to determine if GES improved patients' outcomes in terms of duration and cost of inpatient stay and glycaemic control. We reviewed the patients' case notes and calculated the number of days spent as an inpatient with symptomatic gastroparesis pre and post pacemaker, the total cost of these admissions, and patients' average HbA1c pre and post GES. Mean length of stay in the year pre GES was 81.75 days and 62.25 days in the year post GES (p=0.89). There was also no improvement in glycaemic control following GES. GES has been ineffective in improving length of inpatient stay and glycaemic control in our small patient cohort.

The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review.

INTRODUCTION: Probiotics may benefit irritable bowel syndrome (IBS) symptoms, but randomised controlled trials (RCTs) have been conflicting; therefore a systematic review was conducted. METHODS: MEDLINE (1966 to May 2008), EMBASE (1988 to May 2008) and the Cochrane Controlled Trials Register (2008) electronic databases were searched, as were abstracts from DDW (Digestive Diseases Week) and UEGW (United European Gastroenterology Week), and authors were contacted for extra information. Only parallel group RCTs with at least 1 week of treatment comparing probiotics with placebo or no treatment in adults with IBS according to any acceptable definition were included. Studies had to provide improvement in abdominal pain or global IBS symptoms as an outcome. Eligibility assessment and data extraction were performed by two independent researchers. Data were synthesised using relative risk (RR) of symptoms not improving for dichotomous data and standardised mean difference (SMD) for continuous data using random effects models. RESULTS: 19 RCTs (18 papers) in 1650 patients with IBS were identified. Trial quality was generally good, with nine reporting adequate methods of randomisation and six a method of concealment of allocation. There were 10 RCTs involving 918 patients providing outcomes as a dichotomous variable. Probiotics were statistically significantly better than placebo (RR of IBS not improving=0.71; 95% CI 0.57 to 0.88) with a number needed to treat (NNT)=4 (95% CI 3 to 12.5). There was significant heterogeneity (chi(2)=28.3, p=0.001, I(2)=68%) and possible funnel plot asymmetry. Fifteen trials assessing 1351 patients reported on improvement in IBS score as a continuous outcome (SMD=-0.34; 95% CI -0.60 to -0.07). There was statistically significant heterogeneity (chi(2)=67.04, p<0.001, I(2)=79%), but this was explained by one outlying trial. CONCLUSION: Probiotics appear to be efficacious in IBS, but the magnitude of benefit and the most effective species and strain are uncertain.

Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis.

OBJECTIVE: Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder. Evidence for treatment of the condition with antidepressants and psychological therapies is conflicting. DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs). MEDLINE, EMBASE and the Cochrane Controlled Trials Register were searched (up to May 2008). SETTING: RCTs based in primary, secondary and tertiary care. PATIENTS: Adults with IBS. INTERVENTIONS: Antidepressants versus placebo, and psychological therapies versus control therapy or "usual management". MAIN OUTCOME MEASURES: Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). The number needed to treat (NNT) was calculated from the reciprocal of the risk difference. RESULTS: The search strategy identified 571 citations. Thirty-two RCTs were eligible for inclusion: 19 compared psychological therapies with control therapy or "usual management", 12 compared antidepressants with placebo, and one compared both psychological therapy and antidepressants with placebo. Study quality was generally good for antidepressant but poor for psychological therapy trials. The RR of IBS symptoms persisting with antidepressants versus placebo was 0.66 (95% CI, 0.57 to 0.78), with similar treatment effects for both tricyclic antidepressants and selective serotonin reuptake inhibitors. The RR of symptoms persisting with psychological therapies was 0.67 (95% CI, 0.57 to 0.79). The NNT was 4 for both interventions. CONCLUSIONS: Antidepressants are effective in the treatment of IBS. There is less high-quality evidence for routine use of psychological therapies in IBS, but available data suggest these may be of comparable efficacy.

Probiotics and irritable bowel syndrome: a rationale for their use and an assessment of the evidence to date.

Probiotics, defined as live organisms that, when ingested in adequate amounts, exert a health benefit on the host, have been used for almost a century in the management of a variety of medical disorders, usually on the basis of little evidence. Advances in our understanding of the gut flora and of its relationship to the host, together with progress in microbiology, molecular biology and clinical research have identified important biological properties for probiotics and demonstrated efficacy in a number of gastrointestinal disorders. The clear delineation of a post-infective variety of irritable bowel syndrome (IBS), as well as the description, in a number of studies, of evidence of low-grade inflammation and immune activation in IBS, suggest a role for a dysfunctional relationship between the indigenous flora and the host in IBS and, accordingly, provide a clear rationale for the use of probiotics in this disorder. Other modes of action, including bacterial displacement and alterations in luminal contents, are also plausible. While clinical evidence of efficacy is now beginning to emerge, a review of available trials emphasises the importance of clear definition of strain selection, dose and viability. This is evidently an area of great potential in IBS and deserves further study at all levels.

Serotonergic and non-serotonergic targets in the pharmacotherapy of visceral hypersensitivity.

Visceral hypersensitivity is considered a key mechanism in the pathogenesis of functional gastrointestinal (GI) disorders. Targeting visceral hypersensitivity seems an attractive approach to the development of drugs for functional GI disorders. This review summarizes current knowledge on targets for the treatment of visceral hypersensitivity, and the status of current and future drug and probiotic treatment development, and the role of pharmacogenomic factors.

The PAC-SYM questionnaire for chronic constipation: defining the minimal important difference.

BACKGROUND: The Patient Assessment of Constipation-Symptoms (PAC-SYM) questionnaire is frequently used in clinical trials of constipation. However, the threshold for reduction in total PAC-SYM score used to define a clinical response on this 0-4 point scale has not undergone formal appraisal, and its relationship with clinical benefit as perceived by patients has not been defined. AIM: To determine the minimal important difference in PAC-SYM score, and the optimum cut-off value for defining responders. METHODS: The minimal important difference was estimated using data from six international phase 3/4, double-blind, randomised controlled trials of prucalopride in patients with chronic constipation (NCT01147926, NCT01424228, NCT01116206, NCT00485940, NCT00483886, NCT00488137), with anchor- and distribution-based approaches. Five appropriate patient-reported outcomes were selected as anchors. In addition, receiver operating characteristics (ROC) curve analyses were used to investigate responder discrimination for each anchor. RESULTS: Data from 2884 patients were included. Minimal important difference estimates ranged from -0.52 to -0.63 across the five anchors. Estimates were not affected by study location but were consistently lower for rectal symptoms than for abdominal and stool symptoms. Distribution-based estimates were considerably lower than anchor-based estimates. ROC curve analyses showed optimum cut-off scores for discriminating responders to be similar to anchor-based minimal important difference estimates. CONCLUSIONS: Anchor-based methods gave consistent results for the minimal important difference, at approximately -0.6, and this value was close to the ROC-determined optimal cut-off scores for responder discrimination. This value could be considered in clinical practice. A slightly more conservative threshold (eg -0.75) could be used in clinical trials to reduce the placebo response rate.

Systematic review: Complementary and alternative medicine in the irritable bowel syndrome.

BACKGROUND: Complementary and alternative medical therapies and practices are widely employed in the treatment of the irritable bowel syndrome. AIM: To review the usage of complementary and alternative medicine in the irritable bowel syndrome, and to assess critically the basis and evidence for its use. METHODS: A systematic review of complementary and alternative medical therapies and practices in the irritable bowel syndrome was performed based on literature obtained through a Medline search. RESULTS: A wide variety of complementary and alternative medical practices and therapies are commonly employed by irritable bowel syndrome patients both in conjunction with and in lieu of conventional therapies. As many of these therapies have not been subjected to controlled clinical trials, some, at least, of their efficacy may reflect the high-placebo response rate that is characteristic of irritable bowel syndrome. Of those that have been subjected to clinical trials most have involved small poor quality studies. There is, however, evidence to support efficacy for hypnotherapy, some forms of herbal therapy and certain probiotics in irritable bowel syndrome. CONCLUSIONS: Doctors caring for irritable bowel syndrome patients need to recognize the near ubiquity of complementary and alternative medical use among this population and the basis for its use. All complementary and alternative medicine is not the same and some, such as hypnotherapy, forms of herbal therapy, specific diets and probiotics, may well have efficacy in irritable bowel syndrome. Above all, we need more science and more controlled studies; the absence of truly randomized placebo-controlled trials for many of these therapies has limited meaningful progress in this area.

Prevalence and management of abdominal cramping and pain: a multinational survey.

BACKGROUND: Though functional gastrointestinal complaints are recognised as being common throughout the world, there have been few comparative studies of prevalence. AIM: To compare the prevalence and management of abdominal cramping/pain in nine countries. METHODS: In a two-stage community survey, approximately 1000 subjects were interviewed in each of nine countries to establish the demographics of individuals with abdominal cramping/pain (stage 1) followed by market research-driven interviews with >or=200 sufferers per country (stage 2). RESULTS: 9042 subjects were interviewed in stage 1. Mexico (46%) and Brazil (43%) had the highest prevalence of abdominal cramping/pain; Japan the lowest (10%). Abdominal cramping/pain was more common in women (12-55%) than in men (7-38%). About 1717 subjects participated in stage 2; 65% were women and the average age at symptom onset was 29 years. The frequency of episodes differed between countries, being highest in the US (61% suffered at least once in a week). Sufferers in the US and Latin America reported a higher usage of medications (around 90%) than those in Europe (around 72%). In most countries over-the-counter drugs were principally used. Antispasmodic drugs were most popular in Latin America and Italy, antacids in Germany and the UK. Drug therapy decreased the duration of episodes (by up to 81% in Brazil). CONCLUSIONS: The community prevalence, severity, healthcare seeking and medication usage related to abdominal cramping/pain are high overall, but vary considerably between countries.

Placebo- and paracetamol-controlled study on the efficacy and tolerability of hyoscine butylbromide in the treatment of patients with recurrent crampy abdominal pain.

AIM: To compare the efficacy and tolerability of oral hyoscine butylbromide (hereafter hyoscine) 10 mg t.d.s., paracetamol 500 mg t.d.s. and their fixed combination against placebo in patients with recurrent crampy abdominal pain. METHODS: A total of 1637 patients were entered into a four-arm double-blind study. After a 1 week placebo run-in, they were randomized to 3 weeks of treatment with one of the four therapies with assessments after 1, 2 and 3 weeks. Pain intensity (Visual Analogue Scale) and pain frequency (Verbal Rating Scale) were self-assessed daily. RESULTS: Pain intensity on the Visual Analogue Scale decreased in all treatment groups; the adjusted mean changes from baseline were 2.3, 2.4 and 2.4 cm for the hyoscine, paracetamol and combination groups, respectively, compared with 1.9 cm for the placebo group (all P < 0.0001). The Verbal Rating Scale also showed a statistically significant decrease of 0.7, 0.7 and 0.7 in the hyoscine, paracetamol and combination groups compared with 0.5 in placebo (all P < 0.0001). All treatments were well tolerated: 16%, 14%, 17% and 11% of patients on hyoscine, paracetamol, combination and placebo reported at least one adverse event. CONCLUSIONS: Hyoscine, paracetamol and their fixed combination are effective in the treatment of recurrent crampy abdominal pain and well tolerated if used three times daily continuously for 3 weeks.

Review article: from gastrin to gastro-oesophageal reflux disease--a century of acid suppression.

To commemorate Edkins' discovery of gastrin in 1905, we review a century of progress in the physiology and pathobiology of gastrin and acid secretion especially as it pertains to clinical aspects of gastro-oesophageal reflux disease. Although initially ignored, Edkins' observations eventually led to the enthusiastic investigation of gastrin and acid regulation in peptic ulcer disease, culminating in important therapeutic advances in the management of acid peptic disease. Following the improved understanding of gastric secretory physiology, and the development of acid suppressants with increasing efficacy, the use of surgical intervention for peptic ulcer disease was almost eliminated. Surgery became obsolete with the discovery of Helicobacter pylori. Three other advances are also influencing modern practice: the gastrotoxicity of aspirin and non-steroidal anti-inflammatory drugs is now increasingly appreciated, the role of endoscopy in the diagnosis and therapy of upper gastrointestinal bleeding, and the use of intravenous acid-suppressive agents. The major issue for the future resides within the epidemic of gastro-oesophageal reflux disease. How to diagnose, categorize and treat this condition and how to identify and prevent neoplasia, are the challenges of the new century.

Irritable bowel syndrome: the burden and unmet needs in Europe.

Irritable bowel syndrome affects approximately 10-15% of the European population, although prevalence rates vary depending on the classification used and the country surveyed. This may be due to differences in patterns of medical care and diagnosis of the condition. Up to 70% of individuals with irritable bowel syndrome may not have been formally diagnosed. The disorder affects 1.5-3 times as many women as men and poses a significant economic burden in Europe, estimated at euro 700-euro 1600 per person per year. It also reduces quality of life and is associated with psychological distress, disturbed work and sleep, and sexual dysfunction. It is a chronic disorder, which affects many individuals for more than 10 years. Most patients are managed in primary care, although some are referred to gastroenterologists and other specialists. Patients with irritable bowel syndrome undergo more abdomino-pelvic surgery than the general population. We propose that a positive diagnosis of the condition may avoid the delay in diagnosis many patients experience. We conclude that, in Europe, there are significant unmet needs including lack of familiarity with irritable bowel syndrome, difficulties in diagnosis and lack of effective treatments for the multiple symptoms of the disorder. The development of pan-European guidelines for irritable bowel syndrome will benefit patients with this condition in Europe.

Functional dyspepsia and non-erosive reflux disease. A review.

Functional, or non-ulcer, dyspepsia (FD) and non-erosive reflux disease (NERD), or endoscopy negative reflux disease are common reasons for referral to both the primary care physician and the gastroenterologist. Their aetiology remains largely obscure but both clinical and basic research have revealed much to suggest that these two disease entities are inextricably linked and may represent part of the same disease process. Several theories have been proposed to explain the pathophysiology of functional dyspepsia, including visceral hypersensitivity, delayed gastric emptying, impaired gastric fundus accommodation, Helicobacter pylori infection and psychosocial factors. Recent work suggests that NERD is also a heterogeneous disorder, with some demonstrating abnormal acid exposure and/or sensitivity and others entirely normal 24-h pH studies (functional heartburn). It would appear that the overlap of these two conditions is most apparent between FD and those NERD patients with normal pH studies.

Review article: quality-of-life issues in gastro-oesophageal reflux disease.

The purpose of this review is to explore issues relating to quality of life in gastro-oesophageal reflux disease, examining the range of generic and disease-specific instruments available, their applicability and limitations and to overview the effect of gastro-oesophageal reflux disease on quality of life. Whereas instruments have been developed to assist researchers, there is a paucity of reliable instruments for pragmatic use in the clinical setting. The situation is complicated because there is not necessarily a direct correlation between endoscopic findings and symptom severity and non-erosive reflux disease is now recognized as an important manifestation of gastro-oesophageal reflux disease. However, quality-of-life instruments are useful in evaluating the impact of therapies and interventions, although these are limited, particularly in surgical interventions. Impaired quality of life now forms part of a definition of gastro-oesophageal reflux disease, the impact of which goes beyond the symptoms alone. While the symptoms themselves have a negative effect on sufferers' lives, there are secondary effects caused by impaired physical, emotional and social functioning on productivity. Non-gastrointestinal problems caused by gastro-oesophageal reflux disease also impair quality of life. There is an ongoing need to develop instruments which truly measure the impact of gastro-oesophageal reflux disease and which are readily interpretable to the individual patient and clinician.

Alterations in the colonic flora and intestinal permeability and evidence of immune activation in chronic constipation.

BACKGROUND: Disturbances in bowel function in chronic constipation could result in changes in the colonic flora and lead to disordered immunity and to decreased resistance to pathogenic flora. AIM: To investigate systemic immunity, the faecal flora and intestinal permeability in patients with chronic constipation, under basal conditions and following therapy with the laxative Bisacodyl. METHODS: Intestinal permeability, faecal flora analysis, T- and B-lymphocyte numbers, T-cell subpopulations, lymphocyte proliferation, phagocytosis, intracellular killing of Staphylococcus aureus by neutrophils, as well as circulating levels of immunoglobulins, immune complexes and antibacterial antibodies were assessed in 57 patients with functional constipation. In 12 patients with severely delayed transit, investigations were repeated following therapy with Bisacodyl. RESULTS: Ovalbumin concentrations, in serum, were higher in constipated patients (28.2+/-4.1 ng/ml versus 1.0+/-0.4 ng/ml, p < 0.05). Elevated counts of CD3+, CD4+, CD25+ cells, increased spontaneous proliferation of lymphocytes, elevated titres of antibodies to Escherichia coli and S. aureus, diminished counts of CD72+ B cells, diminished lymphocyte proliferation under phytohemagglutinin (PHA) stimulation and a diminished phagocytic index for both neutrophils and monocytes were found in the constipated patients. Concentrations of Bifidobacterium and Lactobacillus were significantly lower in constipated patients; potentially pathogenic bacteria and/or fungi were increased. Therapy with Bisacodyl resulted in normalisation of the faecal flora, a reduction in ovalbumin concentration and return towards normal for certain immunologic parameters. CONCLUSION: Constipation is associated with striking changes in the faecal flora, intestinal permeability and the systemic immune response. Relief of constipation tends to normalise these findings suggesting that these changes are secondary to, rather than a cause of, constipation.