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Aim: To demonstrate the change and effect of nociceptin/orphanin FQ in the colon of rats with cathartic colon., Methods: The cathartic colon model was established by feeding rats rhubarb for 3 mo, the changes of colonic electromyography were investigated by both suspension muscle strips test and serosal recordings of colonic myoelectrical activity. Immunohistochemical staining (S-P methods) and image analysis were used to determine the changes of nociceptin/orphanin FQ in the proximal colon and distal colon of rats with cathartic colon., Results: Suspension muscle strips test in vitro showed OFQ (10(-9)-10(-6) mol/L) concentration dependently caused an immediate tonic contraction in the isolated colon. But the increase of tension in cathartic colon was less than control groups (P < 0.01). Intravenous administration of OFQ (1 microg/kg) caused phasic contractions in the proximal colon, while the amplitude of phasic contractions caused by OFQ in cathartic colon was much lower than that in the control groups (2.58 +/- 0.41 vs 4.16 +/- 0.53, t = -2.6, P = 0.012). OFQ was highly expressed in the myenteric plexus of the rat colon but not in the muscle cells. The immunoreactivity of OFQ in the proximal colon in cathartic colon rats decreased significantly compared with the control group (P = 0.001)., Conclusion: Colonic smooth muscle of cathartic colon showed low sensitivity to the stimulation of OFQ, suggesting that it might be caused by the abnormal distribution of OFQ or the abnormalities of receptors, leading to the disorganization of dynamic and incoordinated contractions.

Capsule endoscopy is a novel technique for examining the small bowel; however, data interpretation is time consuming and requires expertise. This study aimed to compare the interpretation of capsule endoscopy between an experienced gastroenterologist and a nurse. A total of 50 consecutive videos were viewed independently by a nurse and a physician, both blinded to the referral indications. The nurse had no prior experience with capsule endoscopy. Possible pathology was graded in a pre-agreed standardized manner, with findings described as "relevant," "uncertain," or "irrelevant." Another gastroenterologist, who had knowledge of all the cases including follow-up data and clinical outcomes, independently arbitrated. Findings showed no difference in the number of relevant or uncertain pathologies identified. The nurse reader was more likely to record irrelevant findings (4.7 vs. 2.0 lesions; p < .01) and required more time to read the videos than the physician (mean = 73 vs. 58 min; p < .01). This study shows that a nurse capsule endoscopy reader is as capable as an experienced physician in identifying small bowel mucosal abnormalities on capsule endoscopy. Capsule endoscopy is an area in which nurses could develop as physician extenders.

Background: Current investigations suggest that postinflammatory mechanisms might induce subtle changes in the mucosa and enteric nervous system which cannot be readily detected by routine diagnostic measures in subgroups of functional bowel disorders, especially in postinfectious irritable bowel syndrome (PI-IBS). DEFINITION OF PI-IBS: Characteristic of IBS is a symptom cluster with abdominal pain/discomfort and altered bowel movement without pathologic findings during routine work-up. PI-IBS is characterized by acute onset of symptoms, fever, vomiting, diarrhea and/or positive stool culture., Epidemiology: The incidence of PI-IBS is 10-17% in unselected IBS patients of whom 70% develop diarrhea, 26% alternating bowel movement and 8% constipation., Pathophysiology: Initial gastrointestinal infections might induce subtle ongoing inflammation with consecutive altered mucosal function. Pathomechanisms include mutations within the interleukin-(IL-) 10 promoter polymorphism, hyperplasia of specialized cells including Paneth and enteroendocrine cells (EC) through cytokines as well as inflammatory-mediated modulation of neurones and neurotransmitters within the enteric nervous system. DIAGNOSIS, DIFFERENTIAL DIAGNOSIS, AND THERAPY: It is essential to exclude alarm symptoms. IBS can be positively diagnosed with a sensitivity and specificity of > 90% by standardized questionnaires. Indications of PI-IBS are the acute onset of symptoms, fever, vomiting, diarrhea and/or positive stool culture. Differential diagnoses include lactose intolerance, small bowel bacterial overgrowth, bile acid malabsorption, celiac disease, giardiasis, chronic inflammatory bowel disease, collagenous colitis, and diverticulitis. Therapeutic options in PI-IBS remain symptomatic. So far, no specific anti-inflammatory treatment modalities are available.

Objective: Irritable bowel syndrome after gastroenteritis is well recognized. Our aim was to determine whether postinfective IBS (PI-IBS) has histological or clinical features that are distinct from those of IBS patients with no history of preceding infection., Methods: A total of 75 consecutive IBS outpatients and 36 healthy control subjects completed a questionnaire detailing symptoms, mode of onset, and previous psychiatric history. All underwent a full diagnostic workup including rectal biopsy, which included immunostaining and quantification for lamina propria or intraepithelial T lymphocytes, serotonin-containing enterochromaffin (EC), and mast cells. Patients were divided according to onset of symptoms into PI-IBS (n = 23) or non-PI-IBS (n = 52) patients., Results: Diarrhea predominance occurred more frequently in PI-IBS (70%) than in non-PI-IBS (42%) patients (p = 0.03). A history of previous treatment for anxiety or depression was present in 26% of PI-IBS patients compared to 54% of non-PI-IBS (p = 0.02). Biopsy results for all patients were normal using conventional criteria; however, quantification revealed that PI-IBS showed increased EC cells compared to those of non-PI-IBS patients (p = 0.017) and controls (p = 0.02). Lamina propria T lymphocytes were increased in PI-IBS (p = 0.026) and non-PI-IBS (p = 0.011) patients compared to controls. Mast cells were increased in non-PI-IBS patients (p = 0.054) compared to controls., Conclusions: Individuals with PI-IBS are a clinically distinct subgroup characterized by diarrheal symptoms, less psychiatric illness, and increased serotonin-containing EC cells compared to those with non-PI-IBS.

Background: Post-infectious irritable bowel syndrome is associated with increased serotonin-containing enterochromaffin cells and lymphocytes in rectal biopsies. Animal studies have suggested that steroids reduce the lymphocyte response and suppress some of the post-infectious changes in neuromuscular function., Aim: To evaluate whether steroids reduce the number of enterochromaffin cells and improve the symptoms of post-infectious irritable bowel syndrome., Methods: Twenty-nine patients with post-infectious irritable bowel syndrome underwent a randomized, double-blind, placebo-controlled trial of 3 weeks of oral prednisolone, 30 mg/day. Mucosal enterochromaffin cells, T lymphocytes and mast cells were assessed in rectal biopsies before and after treatment, and bowel symptoms were recorded in a daily diary., Results: Initial enterochromaffin cell counts were increased and correlated with initial lamina propria T-lymphocyte counts (r = 0.460, P = 0.014). Enterochromaffin cell counts did not change significantly after either prednisolone (- 0.8% +/- 9.2%) or placebo (7.9% +/- 7.9%) (P = 0.5). Although lamina propria T-lymphocyte counts decreased significantly after prednisolone (22.0% +/- 5.6%, P = 0.003), but not after placebo (11.5% +/- 8.6%, P = 0.1), this was not associated with any significant treatment-related improvement in abdominal pain, diarrhoea, frequency or urgency., Conclusions: Prednisolone does not appear to reduce the number of enterochromaffin cells or cause an improvement in symptoms in post-infectious irritable bowel syndrome. Other approaches to this persistent condition are indicated.

Goals/background: Irritable bowel syndrome is a common disorder affecting 20% of the general population. It shows certain characteristics with organic bowel diseases. Definition of lymphocytic and collagenous colitis has created a new approach towards chronic idiopathic diarrheas. We searched for the frequency of lymphocytic and collagenous colitis in patients with irritable bowel syndrome., Study: The study group consisted of 30 irritable bowel patients and 20 controls. Multiple biopsies from cecum; ascendant, transverse and descendent colon; sigmoid and rectum were taken sequentially in all patients., Results: We diagnosed 7 out of 30 irritable bowel patients as having lymphocytic colitis (23.3%) but none as having collagenous colitis. In the control group 1 out of 20 patients had lymphocytic colitis (5%) and none had collagenous colitis. Irritable bowel patients had higher rate of lymphocytic colitis association (p < 0.05)., Conclusions: Functional disorders of the bowel should be searched for possible lymphocytic colitis, especially in cases refractory to classical therapies.

Cyclooxygenase-2 (COX-2), the inducible cyclooxygenase isozyme involved in the conversion of arachidonic acid (AA) to biologically active prostanoids, has become the subject of intense interest during the last few years. The recent surge of interest stems from seminal studies that correlated elevated expression of COX-2 with tumor induction and progression, and epidemiological studies that correlated reduced risk of developing certain types of cancers with chronic use of non-steroidal anti-inflammatory agents (NSAIDs). Although these observations were first reported with colorectal cancer (CRC), similar findings have subsequently been made with other types of cancers. A wide spectrum of studies continue to be undertaken in both laboratory and clinical settings to elucidate the mechanisms underlying these anti-tumor effects of COX-2 for potential translation into cancer chemoprevention and therapy. The aim of this article is to present a review of COX genes, the prostaglandin-cyclooxygenase relationship, the role of COX-2 in carcinogenesis and the rationale for targeting COX-2 with NSAIDs for cancer chemoprevention. Special emphasis is given to the role of COX-2 expression in the genesis and progression of colorectal neoplasia, and its correlation with other pathological characteristics of CRC. Preliminary observations on COX-2 expression in inflammatory bowel disease (IBD)-related colorectal neoplasia are also presented.

The low conductance K(+) channel found in human colonocytes was investigated using the patch-clamp technique. The channel is Ca(++)-dependent and is blocked by Ba(++) (5 mM) with a decrease in open probability from 0.42 to 0.19. At -40 mV the slope conductance was 29 pS (using intracellular solution in the pipette). In inside-out patches, inward rectification was seen both with KCl (pipette)/NaCl (bath) solutions as well as KCl/KCl solutions. The rectification could not be affected by omitting Mg(++) from the pipette or the bath solution, neither by exposing the patches to the polyamine spermine (1 mM). Using the Goldman-Hodgkin-Katz equation we show that the permeability decreased in a linear fashion from approximately 5.2 x 10(-14) cm(3)/s to 1.8 x 10(-14) cm(3)/s (-100 to +100 mV), both with and without Mg(++) in the solutions. There was no significant difference in the nominal values of permeability. This property of the K(+) channel may facilitate the hyperpolarization needed to sustain a chloride secretion.

The diagnosis of irritable bowel syndrome (IBS) is arbitrary, being based on criteria defined by consensus rather than specific biologic markers. IBS is merely a consortium of symptoms and as presently defined is no more a disease than dyspnea or fatigue are diseases. In this context, it is therefore not surprising that defining the nature of pain has proven elusive. It is often etiologically assumed that the origins of the pain seen in IBS patients are mechanistically distinct from those of some of the other symptoms of IBS such as diarrhea and constipation. In addition pain is assumed to be part of a continuum ranging from complete absence of any pain to varying degrees of discomfort to severe pain. Both of these assumptions should be challenged: there are no data to support the notion that discomfort and pain experienced in IBS are mediated through different pathways than symptoms such as bloating or that they are not merely the consequence of the physiological perturbations associated with altered bowel function. Similarly one can easily argue that visceral pain may actually be the cause rather than the effect of the altered gut function seen in IBS. Abdominal discomfort could then be the consequence of the latter and be only indirectly related to pain. It is likely that central (such as stress) and peripheral factors (such as intestinal infection) will produce similar symptoms but via markedly different pathways. It may be time to deconstruct IBS as a concept and to approach the clinical picture from a mechanistic rather than a phenomenological perspective, particularly if we are interested in understanding the basis of the symptoms and develop effective therapeutic modalities. Our patients deserve no less.

Aim: To perform a systematic review of the literature with three objectives: (1) to compare the health related quality of life (HRQoL) of patients with irritable bowel syndrome with that of healthy controls; (2) to compare the HRQoL of irritable bowel syndrome patients to those with other diseases; and (3) to examine therapy-associated changes in HRQoL of irritable bowel syndrome patients., Methods: Searches of all English and non-English articles from 1980 to 2001 were performed in Medline and Embase, and two investigators performed independent data abstraction., Results: Seventeen articles met our selection criteria. 13 studies addressed objective no. 1; 11 showed a significant reduction in HRQoL among irritable bowel syndrome patients. Of these, only one study was considered of high quality. Four studies addressed objective no. 2, none of which was considered to be high quality in addressing this objective. Four trials (three of high quality) addressed objective no. 3. One showed that symptomatic improvement with Leupron compared to placebo was accompanied an improvement only in the comparative health domain of the HRQoL. The second study reported significant positive changes in HRQoL after 12 weeks of cognitive behavioural therapy. The third report of two placebo-controlled studies indicated significant improvement with alosetron on most domains of Irritable Bowel Syndrome Quality of Life Questionnaire., Conclusions: (i) There is reasonable evidence for a decrease in HRQoL in patients with moderate to severe irritable bowel syndrome; however, the data are conflicting regarding the impact of irritable bowel syndrome on HRQoL in population-based studies of nonconsulters. (ii) HRQoL in irritable bowel syndrome patients is impaired to a degree comparable to other chronic disorders such as GERD and depression. (iii) A therapeutic response in irritable bowel syndrome-related pain has a corresponding improvement in HRQoL. (iv) Limitations of the literature include focusing on moderate-severe irritable bowel syndrome in referral centres, and lack of appropriate controls

Background & Aims: A role for the mucosal immune system in the pathogenesis of irritable bowel syndrome is suggested by its association with intestinal infections., Methods: To investigate this, we performed histologic and immunohistologic studies on colonoscopic biopsy specimens from 77 patients with symptoms satisfying the Rome criteria and 28 asymptomatic control patients., Results: Histologic assessment of biopsy specimens from symptomatic patients indicated 3 different groups. The first (38 of 77) had normal conventional histology; however, immunohistology showed increased intraepithelial lymphocytes (median, 1.8-fold; range, 1.74-1.86), lamina propria CD3(+) cells (2-fold; range, 1.55-2.91), and CD25(+) cells (6.5-fold; range, 4.98-8.13) compared with asymptomatic controls. The second group (31 of 77) had nonspecific microscopic inflammation and on immunohistology showed similar increases in lymphocyte populations (not significant vs. the uninflamed group) as well as increased numbers of neutrophil leukocytes and mast cells (P < 0.0001 vs. controls and the uninflamed group). The third group (8 of 77) fulfilled histologic and immunohistologic criteria for classic lymphocytic colitis., Conclusions: Examination of colonoscopic biopsy specimens from patients meeting the Rome criteria for a clinical diagnosis of irritable bowel syndrome showed subgroups with normal and abnormal conventional histology. All groups showed increased numbers of activated immunocompetent cells in the intestinal mucosa on quantitative immunohistology, implicating the mucosal immune system in pathogenesis.

Objective: Pouchitis often is diagnosed based on symptoms alone. However, increased stool frequency, urgency, and abdominal pain could be due to a condition resembling irritable bowel syndrome. This study was designed to assess the etiology of bowel symptoms using the Pouchitis Disease Activity Index (PDAI)., Methods: Symptoms, endoscopy, and histology were assessed in 61 consecutive symptomatic patients with ulcerative colitis after ileal pouch-anal anastomosis. Pouchitis was defined as a PDAI score of > or = 7, cuffitis was defined as endoscopic and histological inflammation of the rectal cuff and no inflammation of the pouch, and irritable pouch syndrome (IPS) was defined as symptoms with a PDAI of <7 and the absence of cuffitis., Results: Thirty-one patients (50.8%) had pouchitis, four (6.5%) had cuffitis, and 26 (42.6%) had IPS. Demographics were similar in the three groups. Increased stool frequency, urgency, and abdominal cramps were the most common symptoms in the three groups. Rectal bleeding was seen only in cuffitis (p < 0.001). No patient in the three groups had fever. Twenty-seven patients (87.1%) with pouchitis responded to a 2-wk course of ciprofloxacin or metronidazole with a reduction in PDAI scores of > or = 3. All four patients with cuffitis responded to topical hydrocortisone or mesalamine with a reduction in the PDAI symptom component score of > or = 1. Twelve patients with IPS (46.2%) responded to antidiarrheal, anticholinergic, and/or antidepressant therapies with a reduction in the PDAI symptom component score of > or = 1, whereas the remaining patients had persistent symptoms despite therapy., Conclusions: A substantial number of symptomatic patients after ileal pouch-anal anastomosis do not meet the diagnostic criteria for either pouchitis or cuffitis and have been classified as having IPS. There is an overlap of symptoms among patients with pouchitis, cuffitis, and IPS, and endoscopic evaluation can differentiate among these groups. Distinction between these three groups has therapeutic implications.

Objectives: In healthy subjects, the neural correlates of visceral pain bear much similarity with the correlates of somatic pain. In patients with irritable bowel syndrome, the central nervous system is believed to play a strong modulatory or etiological role in the pathophysiology of the disease. We hypothesize that this role must be reflected in aberrations of central functional responses to noxious visceral stimulation in these patients. To verify this hypothesis, we have induced transient rectal pain in patients and assessed the functional responses of the brain by means of functional magnetic resonance imaging., Methods: Twelve right-handed patients (11 female) were examined. Functional imaging (1.5 T) was performed following a block paradigm, alternating epochs with and without noxious stimulation of the rectum. Rectal pain was induced by inflating a latex balloon. Whole-brain coverage was achieved by means of echo-planar magnetic resonance acquisition., Results: A strong variability of the individual responses to rectal pain was found in patients with irritable bowel syndrome. Significant activations were found in only two patients, and group analysis did not reveal significant activations. In contrast, all patients exhibited significant deactivations. Group analysis revealed significant deactivations within the right insula, the right amygdala, and the right striatum., Conclusions: This study reveals aberrant functional responses to noxious rectal stimulation in patients with irritable bowel syndrome. Those results add grounds to the hypothesis that the central nervous system plays a significant role in the pathophysiology of this syndrome.

Objective: To determine whether intestinal infection plays a role on the pathogenesis of irritable bowel syndrome (IBS)., Methods: 295 patients who had no previous history of functional bowel disorder had received treatment for dysentery (n = 235) or for acute bowel infection at the hospital between April-October, 1998, were followed up for 1 - 2 years and evaluated for their subsequent bowel habits. A cohort study of 243 subjects using their siblings, husbands or wives who did not have dysentery or acute bowel infection at the same period was taken as control. Furthermore, the contents of mRNAs of IL-1alpha, IL-1beta and IL-1ra in the mucosa at the terminal ileum and recto-sigmoid junctions were determined and compared using RT-PCR method in 30 IBS patients and 12 controls., Results: (1) Sixty-six (22.4%) patients were reported to have functional bowel disturbance, and 24 (8.1% total and 10.2% among cases of dysentery) developed IBS in the study group, whereas, only 7.4% had altered bowel habit and 0.8% had IBS in the control group (P < 0.01). (2) The risk of having functional bowel disturbance was higher in patients who suffered from a longer duration (> 8 d, OR = 3.5) of dysentery. (3) The IL-1beta mRNA level in the mucosa of terminal ileum and recto-sigmoid junction of IBS patients with dysentery was higher than that of controls and IBS patients without dysentery (P < 0.01)., Conclusion: Intestinal infection plays a role on the pathogenesis of IBS through some immunological factors.

Infection of mice with the intestinal bacterial pathogen Citrobacter rodentium results in colonic mucosal hyperplasia and a local Th1 inflammatory response similar to that seen in mouse models of inflammatory bowel disease. In these latter models, and in patients with Crohn's disease, neutralization of tumor necrosis factor alpha (TNF-alpha) is of therapeutic benefit. Since there is no information on the role of TNF-alpha in either immunity to noninvasive bacterial pathogens or on the role of TNF-alpha in the immunopathology of infectious colitis, we investigated C. rodentium infection in TNFRp55(-/-) mice. In TNFRp55(-/-) mice, there were higher colonic bacterial burdens, but the organisms were cleared at the same rate as C57BL/6 mice, showing that TNF-alpha is not needed for protective antibacterial immunity. The most striking feature of infection in TNFRp55(-/-) mice, however, was the markedly enhanced pathology, with increased mucosal weight and thickness, increased T-cell infiltrate, and a markedly greater mucosal Th1 response. Interleukin-12 p40 transcripts were markedly elevated in C. rodentium-infected TNFRp55(-/-) mice, and this was associated with enhanced mucosal STAT4 phosphorylation. TNF-alpha is not obligatory for protective immunity to C. rodentium in mice; however, it appears to play some role in downregulating mucosal pathology and Th1 immune responses.

There is considerable interest in the mechanisms that underlie symptom generation in irritable bowel syndrome (IBS) and particularly those mechanisms peripheral to higher centres in the nervous system. While the central nervous system is important in IBS, it is restricted largely to the role of behaviour in stress perception and symptom reporting. The gut and the autonomic nervous system are principal areas of research in identifying mechanisms underlying symptom generation and in the identification of new targets for drug development. While motility changes occur in IBS, they are neither specific nor predictable, and this is one reason why drugs aimed at influencing motility patterns have enjoyed limited success to date. This success has prompted interest in sensory physiology to explain pain and other discomforts expressed by patients with IBS. Patients with IBS exhibit intolerance to rectal distension and other manoeuvres of the gut, while exhibiting normal or raised thresholds for somatic pain. The mechanisms underlying the development of hyperalgesia or allodynia in the gut remain to be determined. In other systems and experimental models, low grade inflammation is a predictable inducer of these states, and recent evidence suggests that a subpopulation of patients with IBS develop chronic symptoms after acute gastroenteritis. This and other inflammatory stimuli may induce a hyperalgesic state and alter motor function in patients with IBS. Substances that mediate these changes are not fully understood, but there is growing recognition of the role of serotonin as a sensitizing agent.

Background: Variation in the characteristics of irritable bowel syndrome patients recruited for clinical trials from different sources could affect their response and the generalizability of trial results., Aim: To describe and compare the characteristics of three different groups of irritable bowel syndrome patients recruited into a 'mock clinical trial.', Methods: We enrolled 245 irritable bowel syndrome patients from three sources: (i) 121 from British primary practitioners; (ii) 72 from California newspaper advertisements; and (iii) 52 from a California gastroenterologist's practice. We obtained demographic, clinical, and Hospital Anxiety and Depression (HAD) Scale data., Results: Most patients were young to middle-aged women; the majority reported symptoms for > 5 years in all three groups. Subject characteristics varied among the groups. Typically, primary care patients were anxious, smokers and daily alcohol drinkers who had sought care recently for irritable bowel syndrome and tried antispasmodic drugs. Their symptoms were intermediate in severity between those of the other two groups. Advertisement subjects were the oldest, most highly educated, most often depressed, and were least likely to have sought care recently for symptoms, which were almost uniformly only moderate in severity. Gastroenterologist patients tended to be anxious and had nearly all sought care recently for symptoms, which were the most severe and most likely to include all three pain-related Rome I criteria., Conclusion: Recruitment methodology affects important characteristics of an irritable bowel syndrome study group.

Different types of stress play important roles in the onset and modulation of irritable bowel syndrome (IBS) symptoms. The physiological effects of psychological and physical stressors on gut function and brain-gut interactions are mediated by outputs of the emotional motor system in terms of autonomic, neuroendocrine, attentional, and pain modulatory responses. IBS patients show an enhanced responsiveness of this system manifesting in altered modulation of gastrointestinal motility and secretion and in alterations in the perception of visceral events. Functional brain imaging techniques are beginning to identify brain circuits involved in the perceptual alterations. Animal models have recently been proposed that mimic key features of the human syndrome.

Aim: To update previous overviews of placebo-controlled double-blind trials assessing the efficacy and tolerance of smooth muscle relaxants in irritable bowel syndrome. METHODS AND TRIALS: A total of 23 randomized clinical trials were selected for meta-analyses of their efficacy and tolerance. Six drugs were analysed: cimetropium bromide (five trials), hyoscine butyl bromide (three trials), mebeverine (five trials), otilium bromide (four trials), pinaverium bromide (two trials) and trimebutine (four trials). The total number of patients included was 1888, of which 945 received an active drug and 943 a placebo., Results: The mean percentage of patients with global improvement was 38% in the placebo group (n=925) and 56% in the myorelaxant group (n=927), in favour of myorelaxants with a mean odds ratio of 2.13, P < 0.001 (95% CI: 1.77--2.58) and a mean risk difference of 22% P < 0.001 (95% CI: 13--32%). The percentage of patients with pain improvement was 41% in the placebo group (n=568) and 53% in the myorelaxant group (n=567): odds ratio 1.65, P < 0.001 (95% CI: 1.30--2.10) and risk difference 18%, P < 0.001 (95% CI: 7--28%). There was no significant difference for adverse events., Conclusion: Myorelaxants are superior to placebo in the management of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is one of the most common entities observed by both primary care physicians and gastroenterologists. Alosetron is a potent and selective serotonin antagonist that recently became the first Food and Drug Administration-approved agent for diarrhea-predominant IBS. However, since approval, significant side effects have been noted with the use of alosetron including severe constipation, fecal impaction, and ischemic colitis. We describe a case of ischemic colitis in a male patient with IBS who was briefly treated with alosetron. Clinical, endoscopic, and pathologic features of the focal colitis strongly suggested ischemia. Symptoms correlated temporally with alosetron use, and symptoms abated with discontinuation of the drug. Endoscopic and pathologic resolution of the colitis were documented.

A case of gastric heterotopia was discovered incidentally on a jejunal resection specimen in a 42-year-old patient operated for Koenig's syndrome present for 10 years. This anomaly was responsible for seven chronic ulcers with strictures at multiple levels. Gastric heterotopia, especially in the jejunum, is a rare anomaly, except in intestinal duplications and Meckel's diverticulum. The various complications are a direct result of the activity of the gastric glands: hemorrhage, Helicobacter pylori enteritis, perforation, chronic ulcer and obstructive syndrome; malignant adenocarcinomatous degeneration has also been reported.

Background/aim: Irritable bowel syndrome (IBS) is characterized by abdominal pain and changes in stool habits. Visceral hypersensitivity (VH) is a key factor in the pathophysiology of IBS. The role of Helicobacter pylori infection in the induction of VH in the upper gastrointestinal tract is controversially discussed. The aim of this study is to evaluate the value of rectal barostat in eliciting abdominal symptoms in patients with IBS in relation to H. pylori infection., Patients and Methods: 31 patients (19 female, 12 male, mean age 45.6 +/- 10 years) with normal colonoscopy and clinical signs of IBS were examined by rectal barostat (pressure-controlled balloon distension in the rectum). Induction of typical abdominal discomfort (far from the balloon) defined the examination positive. Level of nonpainful perception (L1), feeling of defecation (L2), and pain or stool urgency (L3) were registered in comparison with a healthy control group (CG; n = 15, 9 female, 6 male). The H. pylori status was defined by (13)C-urea breath test (n = 46)., Results: Typical abdominal discomfort was induced in 9 patients (pain group, PG) by pressure-controlled rectal distension (H. pylori status: 8 positive, 1 negative). Patients not presenting with abdominal pain to rectal distension (nonpain group, NPG) were all H. pylori negative (p < 0.001). L3 as an indicator of VH was reached at a lower pressure threshold in PG than in NPG or CG (p < 0.05). The perception was not different between NPG and CG (p > 0.05)., Conclusions: The induction of typical abdominal discomfort in patients with IBS by the use of rectal barostat occurred predominantly in H. pylori infected patients and suggests that H. pylori infection may be involved in triggering VH in patients with IBS. Further studies in larger patient groups and after H. pylori eradication therapy are needed to confirm and extend this observation., (Copyright 2001 S. Karger AG, Basel)

Background and Aims: Post-dysenteric irritable bowel syndrome (PD-IBS) develops in up to 25% of patients following Campylobacter enteritis. Our aim was to define the pathological basis of this subgroup of IBS., Methods: Twenty one patients (group 1) underwent serial rectal biopsy and gut permeability testing following acute Campylobacter enteritis as did 10 PD-IBS patients (group 2) and 12 asymptomatic controls., Results: In group 1, enteroendocrine cell (EC) numbers were markedly increased initially and at six and 12 weeks (p<0.001) compared with controls. Gut permeability, as assessed by the lactulose/mannitol ratio, was significantly elevated, initially and at 12 weeks (p<0.005). CD3, CD4, and CD8 lymphocyte counts in the lamina propria and intraepithelial lymphocytes (IEL) were significantly increased initially compared with controls. At visit 1, EC numbers were positively correlated with CD3 counts (r=0.6, p=0.01). At one year, seven subjects (five with persistent loose stools) had rectal biopsies which showed significantly elevated EC, CD3, and IEL counts. In group 2, EC and IEL counts were significantly increased compared with controls (p<0.001), as was gut permeability (p<0.01)., Conclusion: Increased EC, T lymphocytes, and gut permeability are acute changes following Campylobacter enteritis which can persist for more than a year and may contribute to PD-IBS.

Purpose: To evaluate the role of intestinal ultrasound (US) in differentiating organic from functional bowel disease., Material and Methods: We examined with abdominal and intestinal US 313 consecutive outpatients presenting abdominal pain and bowel dysfunction, lasting more than 3 months, with no symptoms or signs of alarm and with no previous diagnosis of organic disease. Our population consisted of 191 women and 122 men, with average age at diagnosis of 36.5 years; 236 of these patients had irritable bowel syndrome, 61 Crohn's disease, and 16 ulcerative colitis. Intestinal wall thickness exceeding 7 mm was considered diagnostic for inflammatory bowel diseases. We compared US findings with the diagnosis made with the conventional diagnostic workup of radiological and endoscopic examinations., Results: Sensitivity of intestinal US for diagnosis of inflammatory bowel diseases was 74% and specificity 98% (respectively 84% and 98% for the diagnosis of Crohn's disease and 38% and 98% for ulcerative colitis), and positive and negative predictive values were both 92%; efficacy was also 92%. The likelihood ratio was 35 if US was positive for inflammatory bowel diseases and 0.26 if bowel wall thickness was less than 7 mm. Diagnostic efficacy was 95% for Crohn's disease and 94% for ulcerative colitis., Discussion: Intestinal US proved to be a valuable tool in diagnosing Crohn's disease. As the first step examination US can show the disease site and suggest further instrumental tests., Conclusions: In our experience intestinal US is an important diagnostic examination for the approach to young patients without symptoms or signs suggestive of organic diseases and can help avoid invasive instrumental examinations.

Mast cells (MC) release potent mediators which alter enteric nerve and smooth muscle function and may play a role in the pathogenesis of the irritable bowel syndrome (IBS). The aim of this study was to determine if MC were increased in the colon of IBS patients compared to controls. Biopsy specimens were obtained from the caecum, ascending colon, descending colon and rectum of 28 patients: 14 IBS (Rome criteria); seven normal; and seven inflammatory controls. Tissue was stained immunohistochemically using a monoclonal mouse antibody for human mast cell tryptase (AA1). Tissue area occupied by tryptase-positive MC (volume density of mast cells) was quantified by image analysis. The number of plasma cells, lymphocytes, eosinophils, neutrophils and macrophages were each graded semiquantitatively (0-4) in haematoxylin and eosin stained sections. Mast cell volume density was significantly (P < 0.05) higher in IBS (0.91 +/- 0.18; CI 0.79; 1.0) than normal controls (0.55 +/- 0.14; CI 0.40; 0.69) in the caecum but not at other sites. Apart from MC, there was no evidence of increased cellular infiltrate in the IBS group. MC were significantly increased in the caecum of IBS patients compared to controls. The multiple effects of the intestinal mast cell alone, or as a participant of a persistent inflammatory response, may be fundamental to the pathogenesis of IBS.

Background: Alosetron is a potent and selective 5-HT3 receptor antagonist, which has been shown to be beneficial in the treatment of female patients with non-constipated irritable bowel syndrome., Aims: To investigate the effect of alosetron on whole gut, small bowel and colonic transit in patients with irritable bowel syndrome (Study 1) and healthy volunteers (Study 2)., Subjects: Thirteen patients with irritable bowel syndrome and 12 healthy volunteers., Methods: Both studies were randomized, double-blind, placebo-controlled with a two-way crossover design, in which each subject received alosetron (2 mg b.d. administered orally) or placebo for 8 days. Mean whole gut transit was determined from the excretion of radio-opaque markers; small bowel transit was determined from rise in breath hydrogen after a meal; and colonic transit and segmental transit were evaluated from abdominal X-ray. In addition, colonic transit was calculated by subtracting small bowel transit time from whole gut transit time., Results: Alosetron increased colonic transit time by prolonging left colonic transit in both patients with irritable bowel syndrome and controls. This resulted in a tendency for the whole gut transit to be delayed in irritable bowel syndrome patients (P=0.128), which was confirmed in controls (P=0.047)., Conclusion: Alosetron delays colonic transit by prolonging left colonic transit. These results add to the body of evidence suggesting that alosetron should have a therapeutic role in patients with non-constipated irritable bowel syndrome.

A large proportion of irritable bowel syndrome (IBS) patients also complain of other functional disorders, such as headache, noncardiac chest pain, low back pain, and dysuria. Some of these features, particularly headache, may have a negative influence on the outcome of IBS. In a large proportion of female IBS patients, sexual intercourse triggers the symptoms, and frequently IBS symptoms exacerbate during menses. These gynecological-type symptoms often mislead the patients to the gynecological clinic, which may imply unnecessary investigations and inappropriate treatments. The diagnostic criteria of the fibromyalgia syndrome include IBS, and hence, the apparent relationship of both syndromes is difficult to analyze. On the other hand, no convincing evidence has been produced to date to sustain an association between IBS and the chronic fatigue syndrome., (Copyright 2000 S. Karger AG, Basel)

Background: The aim of the present study was to investigate the colonic endocrine cells in patients with slow-transit constipation, to ascertain the presence of a possible abnormality., Methods: Ten patients with chronic slow-transit constipation were investigated. As controls, macroscopically and histologically normal tissues from the colon of 12 patients were examined. These patients had polyps, prolapsis, chronic diverticulitis, volvulus, and haemorrhoids. The endocrine cells were stained by immunocytochemistry and quantified by computerized image analysis., Results: There were significantly fewer enteroglucagon- and serotonin-immunoreactive cells in patients with chronic slow-transit constipation. There was no statistically significant difference between patients and controls with regard to the number of peptide YY (PYY)-, pancreatic polypeptide (PP)-, and somatostatin-immunoreactive cells. The cell secretory indexes (CSI) of enteroglucagon- and somatostatin-immunoreactive cells were significantly decreased. There was no statistically significant difference in the CSI between the patients and controls with regard to PYY-, PP-, and serotonin-immunoreactive cells., Conclusion: The changes in colonic endocrine cells in patients with slow-transit constipation may be one cause of the decreased motility in the colon and consequent development of constipation.

Intestinal neuronal dysplasia (IND) was initially described as a developmental abnormality of the submucous plexus in children. In recent years this abnormality has also been observed in adults with chronic constipation. The aim of this study was a morphometric characterization of this disease. The investigation was performed with 10 adults with IND, compared with 10 healthy control probands. The best diagnostic indicator of IND proved to be the detection of 6-10 giant ganglia with more than 7 nerve cells in 15 biopsy sections. IND is an interesting cause of chronic constipation which can be histologically verified.

It is unclear whether human intestinal intraepithelial T lymphocytes (iIEL) are resting or activated cells. To address this question, an improved isolation procedure was developed for small bowel iIEL, which were analysed by two-colour flow cytometry and compared with resting and mitogen-activated peripheral blood lymphocytes. iIEL expression of CD44 isoforms, Bcl-2 and Ki67 antigen was also determined in tissue sections. iIEL expressed CD69 at levels comparable with 48-72 h phytohaemagglutinin blasts, but did not express CD25 or CD95. iIEL were Bcl-2+ but not Ki67+. alphaEbeta7 and alpha4B7 expression was relatively high, whereas alphaLbeta2, CD5 and CD28 were expressed at low density. Isolated iIEL expressed CD44 (core epitopes) at lower levels than peripheral blood lymphocytes, although almost all CD44 contained splice variant 6 (CD44v6). Peripheral blood lymphocytes expressed CD44 at very high density, but little CD44v6, even after activation. However, in tissue sections, iIEL showed differential labelling with CD44 core epitope antibodies and no detectable CD44v6, implying CD44 receptor occupancy or epitope masking in situ. Thus, normal iIEL express a quasi-activated phenotype with unusual patterns of adhesion receptors, which may act as costimulatory elements. These may permit iIEL to assume effector functions, with absence of CD25 preventing entry into the cell cycle, thereby maintaining an apoptosis-resistant phenotype.

Background: Both psychological and physiological disturbances have been implicated in the aetiopathogenesis of irritable bowel syndrome (IBS)., Aims: To investigate how the psychological factors act, and the involvement of infective and physiological factors., Methods: Consecutive patients hospitalised for gastroenteritis reported life events for the previous 12 months, and past illness experiences on standardised questionnaires. They also completed psychometric questionnaires for anxiety, neuroticism, somatisation, and hypochondriasis. In some patients, rectal biopsy specimens were obtained during the acute illness and at three months postinfection., Results: Ninety four patients completed all questionnaires: 22 patients were diagnosed with IBS after their gastroenteritis (IBS+), and 72 patients returned to normal bowel habits (IBS-). IBS+ patients reported more life events and had higher hypochondriasis scores than IBS- patients. The predictive value of the life event and hypochondriasis measures was highly significant and independent of anxiety, neuroticism, and somatisation scores, which were also elevated in IBS+ patients. Rectal biopsy specimens from 29 patients showed a chronic inflammatory response in both IBS+ and IBS- patients. Three months later, specimens from IBS+ patients continued to show increased chronic inflammatory cell counts but those from IBS- patients had returned to normal levels. IBS+ and IBS- patients exhibited rectal hypersensitivity and hyper-reactivity and rapid colonic transit compared with normal controls, but there were no significant differences between IBS+ and IBS- patients for these physiological measurements., Conclusion: Psychological factors most clearly predict the development of IBS symptoms after gastroenteritis but biological mechanisms also contribute towards the expression of symptoms.

Morphometry was carried out of the surface epithelium, of crypts as a whole and their epithelium in rectal mucosa (RM) biopsy specimens from patients with irritable colon syndrome (ICS) and chronic non-infectious unspecified colitis (ChNUC). Of the RM morphometric parameters, it is the intestinal crypt external diameter (CED) that exhibited most extensive correlations, which fact enabled the authors to use CED for systematization of ICS and ChNUC patients. Interrelationship was established between CED, ICS clinical picture and ChNUC rates.

Background: The production of free radicals is increased in inflammatory bowel disease, and trace elements are crucial components of several antioxidants. Trace elements deficiency may therefore compromise the defense against oxidative damage. The aims of this study were to measure plasma and tissue concentration of trace elements and antioxidants and to relate this to disease activity., Methods: A 10-ml blood sample and six colonic biopsy specimens were obtained from 24 patients with either active ulcerative colitis or in remission and 10 patients with irritable bowel syndrome for measurement of trace elements and trace element-dependent enzymes., Results: Patients with moderately active disease had significantly lower plasma iron, selenium, and glutathione peroxidase levels than patients in remission and controls, whereas no significant differences were found between the zinc and copper values of patients and controls. Mucosal concentrations of zinc and metallothionein were reduced, whereas iron and glutathione peroxidase concentrations were increased in patients with endoscopically active disease as compared with controls and patients in remission., Conclusions: Patients with ulcerative colitis have altered plasma and tissue levels of trace elements and antioxidant-related enzymes. The resulting reduced protection against free radicals may contribute to the inflammatory process.

The author proceeds from the belief that it is the dystrophic changes and disturbances in the regeneration of the intestinal epithelium that play a decisive role in the pathogenesis and morphogenesis of irritable intestinal syndrome and chronic non-infectious undefined colitis. The above alterations develop secondary to the action of harmful factors and disturbed trophic influences of neurohumoral systems of regulation during different stages of stress. At the same time the synthetic leu-enkefalin dalargin is endowed with a marked antistressor activity as well as ability to strikingly improve the regeneration of the epithelium. This was reason why therapeutic efficacy of dalargin has been given a trial in the above pathologies. Positive dynamics of symptoms of the conditions in question has been shown as well as of the histologic picture of colonic mucosa biopsies during the course of treatment of the above ailments with dalargin.

Morphofunctional state was studied of intestinal enteroendocrine cells in biopsies obtained during fibrocolonoscopy using Grimelius's argyrophil reaction, as was immune status, condition of vegetative nervous system, together with the psychological examination being conducted. Most of the systems examined showed alterations peculiar to the stage of resistance of the general-adaptation syndrome. Dependence was found out between the morphofunctional state of endocrinocytes and type of disorder in the motor function of the intestine, parameters characterizing the vegetative regulation. Statistical analysis of the results obtained showed that most of the studied parameters of different systems have come in a single-modal distribution of variants (sequences), which fact suggests that pathologic processes in irritable colon syndrome (ICS) and chronic non-infectious undefined colitis (ChNIUC) might be uniform. Based on the above results the authors believe ICS and ChNIUC to be different stages of the same pathologic process. It can be asserted, to the authors' thinking, that ICS and ChNIUC are dystrophic, disregenerative, rather than inflammatory processes, as to their pathogenetic mechanisms.

Aim: To identify simple, objective, accurate histological criteria for distinguishing acute infective-type colitis, chronic idiopathic inflammatory bowel disease, and irritable bowel syndrome on rectal biopsy in patients with acute onset diarrhoea at first presentation, one to 10 weeks after onset., Methods: Cell counts and measurements of mucosal architecture were made on initial rectal biopsies from 18 patients with acute infective-type colitis, 17 patients with first acute presentation of chronic idiopathic inflammatory bowel disease, and 23 patients with irritable bowel syndrome. The data were analysed by ANOVA and discriminant analysis., Results: Lamina propria cells were mainly in the upper third in irritable bowel syndrome patients. Increased lamina propria cellularity, mainly in the middle third, and numbers of crypt intraepithelial neutrophils distinguished acute infective-type colitis from irritable bowel syndrome in 93% of cases. Chronic idiopathic inflammatory bowel disease differed from irritable bowel syndrome and acute infective-type colitis in a decreased number of crypts and altered crypt architecture. Chronic idiopathic inflammatory bowel disease showed higher lamina propria cellularity, especially in the basal third, with an increased number of lamina propria neutrophils. On discriminant analysis, crypt numbers distinguished 86% of the cases of chronic idiopathic inflammatory bowel disease from the other groups., Conclusion: At one week or more from onset, acute infective-type colitis is characterised by a superficial increase in lamina propria cellularity, with only a slight increase in the number of polymorphs. At this stage, chronic idiopathic inflammatory bowel disease is characterised by a transmucosal increase in cellularity together with crypt loss and architectural abnormality. Thus, measurement of mucosal architecture establishes simple, accurate, objective criteria for routine biopsy diagnosis of chronic idiopathic inflammatory bowel disease from acute infective-type colitis and irritable bowel syndrome at initial presentation, one to 10 weeks after onset.

To investigate whether the mast cells (MC) of the ileocecal junction (ICJ) is elevated in the irritable bowel syndrome (IBS) and the possible roles of the MC in IBS, the biopsies of ICJ were stained specifically by histochemistry for the MC in the IBS group (n = 20) and the normal group (n = 19). The structure relation between MC and nerves was studied through an electronic microscopy and an immunohistochemical method demonstrating neuronspecific enolase. The results demonstrated that the number of the MC of ICJ was significantly elevated in the IBS (P = 0.019) and that mast cells were close to nerves which were often unmyelinated nerves in lamina propria. The results indicate that the MC of ICJ may be responsible for the pathophysiology of the IBS. We conclude that the MC of ICJ may be a mediator between the gut and the nervous system in the IBS, and that the mast cell stabilizer or the antagonists of the mast cell products may have potential treatment effects on the IBS.

Many patients with interstitial cystitis (IC) also have irritable bowel syndrome (IBS), both of which occur overwhelmingly in women, are characterized by pain, and worsen under stress. Bladder and colon biopsies of a female patient with both IC and IBS were evaluated immunohistochemically. There were 40 +/- 10 mast cells (MC)/mm2 (normal, less than 10) in the bladder, which were degranulated. The colon contained 148 +/- 11 MC/mm2 (normal, less than 50), mostly close to numerous substance P (SP)-positive nerves. Histamine, methylhistamine, and the unique MC enzyme tryptase were evaluated in 24-hour urine during two flare-ups. These results may help explain the concurrent presentation and the painful nature of these syndromes.

The role of cholestasis and ileal dysfunction on sterol metabolism was studied in 79 patients with inflammatory bowel diseases (IBDs) and in 23 irritable bowel syndrome (IBS) controls by determining serum sterol/cholesterol proportions. The sterols included cholesterol precursors (delta 8-cholestenol, desmosterol and lathosterol), markers of cholesterol synthesis, cholestanol and plant sterols (campesterol and sitosterol), markers of cholesterol absorption and biliary secretion. The IBD patients were subgrouped into distal ulcerative colitis (dUC, n = 21), pancolitis (pUC, n = 29), ileal Crohn's disease (iCD, n = 20) and colonic Crohn's disease (cCD, n = 9). The cholestanol proportions were increased in the 3 colonic IBD groups, up to two times in cCD patients and seven times in a case with clinically overt primary sclerosing cholangitis, but were within the control IBS levels in the patients with iCD. The sitosterol, but not campesterol, proportion was significantly increased only in the pUC group. In the iCD group only the serum precursor sterol proportions, especially those for delta 8-cholestenol and lathosterol, were elevated probably due to ileal dysfunction induced bile acid malabsorption and compensatorily increased cholesterol synthesis. In conclusion, the findings suggest that the increased cholestanol proportion in colonic IBD is determined mainly by impaired biliary elimination of this sterol, while in ileal affision the dominating change in sterol balance is activated cholesterol synthesis. Thus increased serum cholestanol is a novel finding in colonic IBD, apparently indicating the presence of subclinical cholestasis in a marked number (20-50%) of IBD patients.