Effect of extrinsic denervation on muscarinic neurotransmission in the canine ileocolonic region.

To explore the hypothesis that denervation hypersensitivity increases ileocolonic motor activity after extrinsic denervation, we compared muscarinic neurotransmission in canine ileocolonic loops that were isolated and either extrinsically innervated or extrinsically denervated. We recorded ileal, ileocolonic sphincter (ICS) and colonic pressures, and colonic tone, compliance and relaxation during ileal distention. Muscarinic effects were probed by neostigmine, and minimally effective doses of muscarinic receptor antagonists. Denervation augmented ileal, ICS and colonic contractile activity; colonic high-amplitude propagating contractions (HAPCs) were also augmented; colonic relaxation during ileal distention was abolished. Neostigmine induced HAPCs in both loop preparations. Pirenzipine (M1 antagonist) reduced ileal contractile activity in all loops and reduced colonic relaxation during ileal distention in innervated loops. Pirenzipine also reduced colonic tone and colonic HAPCs, more in denervated loops. Darifenacin (M3 antagonist) reduced ileocolonic contractile activity and tone more than did AF-DX 116 (M2 antagonist) in all loops. Cholinergic receptor subtypes modulate different facets of ileocolonic motor activity in the canine ileocolonic region. Increased sensitivity at M1 muscarinic receptors may partly account for the effects of extrinsic denervation.

Model of rapid gastrointestinal transit in dogs: effects of muscarinic antagonists and a nitric oxide synthase inhibitor.

Our aims were to establish a canine model of rapid gastrointestinal transit, and to test the effects of muscarinic receptor antagonists (atropine, pirenzepine, AF-DX116, and darifenacin), and an NOS inhibitor, L-nitro-N-arginine (L-NNA) in this model. For gastric emptying and small bowel transit, 99mTc-labelled DTPA were added to a meal of skimmed milk (236 mL) that contained 2.4 g of magnesium hydroxide. Regional colonic transit was measured by111In-labelled beads placed in a capsule that released isotope in the proximal colon. Scintiscans were taken at regular intervals and indices of transit were calculated. Drugs were administrated intravenously. Gastric emptying, small bowel and colonic transit were rapid. Atropine and darifenacin (a selective M3 antagonist) delayed gastric emptying and colonic transit, the selective M1 and M2 muscarinic antagonists did not. The muscarinic blockers did not slow small bowel transit. L-NNA delayed small bowel and colonic transit but did not slow gastric emptying. A model suitable for the preclinical study of antidiarrhoeals was established. M3 receptors are important in the control of gastric emptying and colonic transit, and NOS inhibition slowed small bowel and colonic transit.

Guidelines for adults on self-medication for the treatment of acute diarrhoea.

Acute uncomplicated diarrhoea is commonly treated by self-medication. Guidelines for treatment exist, but are inconsistent, sometimes contradictory, and often owe more to dogma than evidence. An ad hoc multidisciplinary group has reviewed the literature to determine best practice. In general it is recognized that treatment of acute episodes relieves discomfort and social dysfunction. There is no evidence that it prolongs the illness. Self-medication in otherwise healthy adults is safe. Oral loperamide is the treatment of choice. Older anti-diarrhoeal drugs are also effective in the relief of symptoms but carry the risk of unwanted adverse effects. Oral rehydration solutions do not relieve diarrhoea, and confer no added benefit for adults who can maintain their fluid intake. Probiotic agents are, at present, limited in efficacy and availability. Antimicrobial drugs, available without prescription in some countries, are not generally appropriate for self-medication, except for travellers on the basis of medical advice prior to departure. Medical intervention is recommended for the management of acute diarrhoea in the frail, the elderly (> 75 years), persons with concurrent chronic disease, and children. Medical intervention is also required when there is no abatement of the symptoms after 48 h, or when there is evidence of deterioration such as dehydration, abdominal distension, or the onset of dysentery (pyrexia > 38.5 degrees C and/or bloody stools).

Direct clinical evidence for spinal hyperalgesia in a patient with irritable bowel syndrome.

OBJECTIVE: Our objective was to evaluate GI motor and sensory function and spinal cord testing in a patient with severe irritable bowel syndrome. METHODS: A patient is described who underwent an extensive assessment of GI motor and sensory function including transit studies, colonic and rectal barostat studies, sensory and manometric studies of the small bowel, and colon and anorectal physiology testing. The patient also underwent testing with spinal cord stimulation and spinal drug delivery as part of a pain management assessment. RESULTS: The viscerosomatic referral pain pattern resulting from rectal distention was consistent with spinal hyperalgesia. The patient underwent testing for spinal cord stimulation and spinal drug delivery. CONCLUSION: This novel finding provides direct clinical evidence for the presence of spinal hyperalgesia in a patient with irritable bowel syndrome, consistent with the existing indirect clinical evidence and animal data.

Rectal compliance, capacity, and rectoanal sensation in fecal incontinence.

OBJECTIVE: Assessments of the pathophysiology of fecal incontinence are skewed toward anal sphincter function; however, rectal compliance, rectoanal sensation and capacity may also be relevant. The aim of this study was to evaluate the usual and some novel diagnostic approaches in fecal incontinence. METHODS: In 22 unselected patients with fecal incontinence (21 F, 33-75 yr), we quantified: 1) symptoms, anorectal manometry, and anal ultrasound; 2) anal perception of temperature and light touch; 3) rectal sensitivity and compliance to distension; and 4) rectal reservoir function. Control values were obtained from two groups of 11 (seven F, 32-53 yr), and 32 (18 F, 19-44 yr) volunteers. RESULTS: Patients had urge (14), passive (four), or combined (four) fecal incontinence; symptoms were mild in three, moderate in nine, and severe in 10 patients. Most had low sphincteric pressures and ultrasonic abnormalities. Temperature perception was impaired (p < 0.05) in incontinent patients, to a greater extent in the proximal anal canal and in patients with passive, as opposed to urge, incontinence. Intraluminal pressures for sensations of rectal distension were lower in incontinent patients (p = 0.02). Artificial stools elicited sensations of rectal filling at lower volumes than did a barostat bag, and in patients with urge, as opposed to passive, incontinence. In patients and controls, the sensation of urgency was associated (r2 = 0.2, p < 0.01) with rectal compliance. CONCLUSIONS: We confirm that temperature sensation is impaired, and perception of rectal distension is not always reduced in fecal incontinence. Artificial stool tended to induce sensations at lower volumes than did balloon inflation. Altered sensory mechanisms may contribute to the pathophysiology of fecal incontinence.

Slow transit constipation.

Slow transit constipation is a clinical syndrome predominantly affecting young women, characterized by constipation and delayed colonic transit, occasionally associated with pelvic floor dysfunction. The disorder spans a spectrum of variable severity, ranging from patients who have relatively mild delays in transit but who are otherwise indistinguishable from irritable bowel syndrome patients at one extreme, to patients with colonic inertia or chronic megacolon at the other extreme. Potential mechanisms for impaired colonic propulsion include fewer colonic HAPCs or a reduced colonic contractile response to a meal. The cause of the syndrome is unclear. The treatment is primarily medical; surgery is reserved for patients with severe disease or colonic inertia. Recognition and treatment of pelvic floor dysfunction is crucial for patients treated medically or surgically. Collaborative studies are necessary to determine the pathophysiology of this disorder and to ascertain the efficacy of novel prokinetic agents.

Increased eosinophil infiltration and degranulation in colonic tissue from patients with collagenous colitis.

OBJECTIVE: Eosinophils infiltrate the colonic mucosa of patients with collagenous colitis (CC), although the pathogenetic implications are unknown, including whether these eosinophils are activated and degranulate in situ. We examined eosinophil infiltration and degranulation in the intestines of patients with CC by immunofluorescence for eosinophil granule major basic protein (MBP). METHODS: We used both conventional histology (hematoxylin and eosin) and indirect MBP immunofluorescence histochemistry on colon biopsy specimens from patients with CC (n = 21) and from healthy controls (n = 9). Scoring of histological features was performed on hematoxylin and eosin-stained sections on a 0 to 3 scale. Eosinophil infiltration and degranulation, as quantified by extracellular MBP staining, were scored in each specimen on a 0 to 4 scale. RESULTS: The inflammatory infiltrate of the lamina propria, the thickness of the collagen band, the numbers of intraepithelial lymphocytes, and degree of epithelial cell damage were all significantly increased in patients with CC as compared to controls (p < 0.0001). Scores for both eosinophil infiltration and degranulation were also significantly higher in the CC group compared to controls (p < 0.0001). The degree of infiltrating eosinophils by hematoxylin and eosin was correlated with eosinophil infiltration and degranulation by MBP immunostaining; however, no other correlations were found between eosinophil infiltration or degranulation by immunofluorescence and any of the histological parameters measured in the CC group. CONCLUSIONS: Eosinophil infiltration and degranulation are increased in the colonic mucosa of patients with CC compared to healthy controls. Eosinophils and their cytotoxic granule proteins could be involved in the pathogenesis of CC. Further studies will be necessary to elucidate the mechanisms of eosinophil activation in CC.

Characteristics and evolution of extraintestinal manifestations associated with ulcerative colitis after proctocolectomy.

AIMS: Describe the characteristics of extraintestinal manifestations complicating ulcerative colitis present preoperatively and determine their evolution after surgery. METHODS: Between 1976 and 1986, 281 patients with ulcerative colitis exhibiting one or more extraintestinal manifestations (EIM) before either IPAA (n = 147), Brooke ileostomy (n = 71), Kock pouch (n = 48) or ileorectostomy (n = 15) were assessed retrospectively. The clinical evolution of each manifestation was classified as having disappeared, improved, remained unchanged or aggravated postoperatively. An efficacy index was designed to assess the ratio of the number of cases cured or improved over the number of cases unchanged or aggravated. The relationship between EIM and gender, age, duration of disease and the type of surgery was also ascertained. RESULTS: 433 EIM were observed in 281 patients. The most common were arthralgias of the large joints (n = 146), of the sacroiliac joint (n = 59) and the small joints (n = 51). In comparison to patients without EIM having received the same operation during the same period of time, EIM were seen more often in women, younger patients, than those with longer duration of disease and the ileoanal anastomosis group. 60% had only one EIM at a time. Based on the efficacy index, thromboembolic accidents and erythema nodosum were the most commonly cured or improved. Ocular manifestations and primary sclerosing cholangitis were unaffected. The other EIM responded favorably but variably with improvement in two thirds of patients. The presence of a rectal remnant (IRA) or ileal reservoir did not affect the evolution of the EIM. CONCLUSIONS: Thromboembolic complications which are life-threatening, erythema nodosum and arthralgia of the small and large joints which impair quality of life, benefited the most from proctocolectomy. Those conditions may be considered preoperatively when making the decision for surgery.

American Gastroenterological Association Medical Position Statement: guidelines on constipation.

This document presents the official recommendations of the American Gastroenterological Association (AGA) on constipation. It was approved by the Clinical Practice and Practice Economics Committee on March 4, 2000, and by the AGA Governing Board on May 21, 2000.

AGA technical review on constipation. American Gastroenterological Association.

This literature review and the recommendations therein were prepared for the American Gastroenterological Association Clinical Practice and Practice Economics Committee. The paper was approved by the Committee on March 4, 2000, and by the AGA Governing Board on May 21, 2000.

Concurrence of inflammatory bowel disease and multiple sclerosis.

OBJECTIVES: To quantify the coexistence of inflammatory bowel disease (IBD) and multiple sclerosis (MS) and to characterize the diseases when they coexist. PATIENTS AND METHODS: In this retrospective study of medical records spanning 1950 through 1995, the diagnoses of Crohn disease (CD), ulcerative colitis (UC), and MS were based on review of inpatient and outpatient records by a gastroenterologist and a neurologist. RESULTS: We identified 4 residents of Olmsted County, Minnesota, with IBD (3 UC, 1 CD) who had concurrent, clinically definite MS; all had mild neurologic disease with little disability. These comprised 1% of the IBD and 1.8% of the MS cohort. The CD patient had undergone terminal ileal resection; of the UC patients, 2 had pancolitis, and 1 had proctosigmoiditis. The observed prevalence of MS at onset of IBD was 3.7 times the expected (95% confidence interval, 0.8-10.8). We also reviewed the records of 32 referral patients with both diagnoses. Disability from MS was moderate at median follow-up of 8.5 years. By 15 years, ambulation was impaired in most patients. Neurologic disability was similar between patients with CD and UC. CONCLUSIONS: Concurrence of the 2 diseases was greater than expected. Although MS and IBD may share common predisposing factors, not enough information is available to speculate about possible mechanisms.

Motilides accelerate regional gastrointestinal transit in the dog.

BACKGROUND: Motilides have prokinetic effects on the upper gut during fasting, increasing the strength of antral contractions and stimulating gastroduodenal phase 3 sequences. Effects on the distal gut, and postprandially, are less well documented. AIM: To evaluate dose-response effects of motilin and erythromycin on gastric emptying, small bowel and colonic transit in the dog using a validated scintigraphic technique. METHODS: For gastric emptying and small bowel transit, 99mTc labelled beads were added to a meal of dog chow (450 kcal). Regional colonic transit was measured by 111In labelled beads placed in a capsule which dissolved and released radiation into the proximal colon. Scintiscans were taken at regular intervals and indices of whole-gut transit were calculated. Drugs were given by slow intravenous administration. RESULTS: In the doses used, motilin accelerated regional colonic transit but did not hasten gastric emptying or small bowel transit. Single or repeated doses of motilin had similar effects on colonic transit. Erythromycin accelerated gastric emptying, small bowel transit and regional colonic transit. CONCLUSIONS: Motilin receptors are apparently present in the canine small bowel and colon. Postprandially, motilides accelerate transit in the distal gut.

Alcohol-related diarrhea.

Abstract Alcohol generates a large caloric yield without supplying any essential nutrients; alcoholics may thus maintain body weight while suffering from malnutrition. In addition, diarrhea is a common complaint of both acute and chronic alcoholics. Here, we review the effects of alcohol on gastrointestinal morphology, function, its nervous system and motility. Acute morphological changes such as erosions, inflammatory cell infiltrations and microvascular changes are seen in the stomach and small intestine in acute alcoholics. In addition, atrophic gastritis, reduced villous height and decreased mucosal surface area of the small intestine have been described in chronic alcoholics. Acute administration of alcohol inhibits absorption of nutrients and fluids, and can stimulate secretion of water and electrolytes. Bacterial overgrowth in the proximal small intestine and decreased pancreatic secretions have been also described in chronic alcoholics. The well-known deleterious effects of alcohol on the central nervous system raise the possibility of similar acute and chronic effects of the enteric nervous system. Such effects could alter motility and transit. Indeed, esophageal dysmotility and delayed gastric emptying have been observed with high concentrations of alcohol in experimental studies and in chronic alcoholics. Small bowel motility and transit may be abnormal in both acute and chronic alcoholics, and colonic propulsive motility is increased after acute administration of alcohol. Any, or all, of these changes in gastrointestinal functions may contribute to diarrhea in acute binge drinkers and chronic alcoholics. Unfortunately, there is a lack of systematic studies of the pathophysiology of alcohol abuse, and an integrating concept of the diarrhea of alcoholics is still not possible.

Irritable bowel syndrome: making sense of it all.

Though the basic science of the irritable bowel syndrome is far from certain, and the clinical science is often confusing, it is still possible to make some sense of the syndrome in a clinical context. These common complaints of altered bowel patterns, pain and bloating are extremely common and vary greatly in the impact they have on person's lives. From 'non-patients' who do not present for medical care to those who seek referral to multiple specialists, the spectrum is well known. If sense is to be made, the physician must understand the patient's major symptoms, how and to what degree they disturb their lifestyle, what is the patient's knowledge about and understanding of the syndrome, what has been done before, and why the patient is now presenting. What are the expectations and potential frustrations anticipated with this present consultation? A positive diagnostic approach can be taken but care is necessary to assuage lingering fears of organic disease, to correct misconceptions of the syndrome, to settle existing frustrations of the patient, and to educate. With these approaches, managing irritable bowel syndrome can be rewarding, though demanding.

Surreptitious laxative abuse: keep it in mind.

The clinical example is one of diarrhea induced by the surreptitious use of laxatives. A 45-year-old man had a 3-year history of diarrhea, which had been fully investigated, without a cause having been identified. His general health appeared to be affected little, but he had the clinical features of an associated depressive illness. The diagnosis of laxative abuse was supported by the finding of abnormally high concentrations of magnesium in fecal water. He admitted initially, and later denied, the surreptitious ingestion of laxatives. This example is discussed with regard to features that were typical and atypical of the syndrome of laxative abuse. The significant points to be appreciated are 1) that any chronic, watery diarrhea that has eluded diagnosis after an adequate investigation is possibly self-induced, and 2) that awareness of this syndrome and its prevalence in selected cohorts can lead to direct and inexpensive documentation of the diagnosis.

The effects of biofeedback on rectal sensation and distal colonic motility in patients with disorders of rectal evacuation: evidence of an inhibitory rectocolonic reflex in humans?

OBJECTIVE: Abnormalities of descending colon motility reported in a subset of patients with rectal evacuation disorders are consistent with a rectocolonic inhibitory reflex. Our aims were to evaluate distal colon motor function and rectal sensation in such patients and assess effects of biofeedback (BF) training on these functions. METHODS: Seven patients (five women, two men; mean age 36 yr) with rectal evacuation disorders were studied before and after 10-days biofeedback training; six healthy volunteers (five women, one man; mean age 30 yr) were studied once. Colonic compliance, motility, sensation thresholds, and perception scores during standardized rectal distentions were measured using two barostat-manometry assemblies inserted into the cleansed colon with the aid of flexible sigmoidoscopy. RESULTS: Sigmoid compliance, fasting, and postprandial motility index, and perception thresholds were similar in controls and patients before and after biofeedback training. Postprandial sigmoid tone tended (p = 0.09) to be lower in patients than controls; after biofeedback, postprandial tone was comparable to that in controls. Rectal urgency scores at 24 mm Hg distention were greater in patients than in controls (p = 0.02 for both). After biofeedback, there were trends for lower perceptions of urgency to defecate (7.6 +/- 1.1 cm pre- vs 5.3 +/- 1.5 post-; p = 0.04) at 24 mm Hg; conversely, gas sensation at 12 mm Hg was higher (1.2 +/- 0.5 cm pre- vs 3.3 +/- 0.6 post-; p = 0.05). CONCLUSIONS: Normalization of rectal evacuation and postprandial sigmoid tone in patients with evacuation disorders by biofeedback training supports the presence of a rectocolonic inhibitory reflex. Effect of biofeedback on rectal sensation in these patients requires further study.

Videoendoscopic diagnosis of esophageal motility disorders.

BACKGROUND: Esophageal motility disorders are usually diagnosed by manometry. We evaluated videoendoscopy as a diagnostic test. METHODS: In this study, 20 patients with achalasia, 13 with scleroderma, and 33 control subjects had a standard endoscopic examination followed by protocol videotaping of swallows to observe contractions in the esophagus and in the lower esophageal sphincter. Tapes were later reviewed by 2 blinded observers who recorded their motility findings and diagnoses. RESULTS: In the mid esophagus at 25 cm, lumen-occluding peristaltic contractions were identified in 26 of 33 control subjects versus 1 of 20 achalasia (p < 0.001) and 3 of 13 scleroderma patients (p < 0.005). As viewed in the lower esophagus, the lower esophageal sphincter opened normally in 31 of 33 control subjects versus 1 of 20 achalasia (p < 0.001). In scleroderma, the sphincter never closed in 12 of 13 patients (p < 0. 001 versus control subjects). A diagnostic sequence of sphincter opening followed by contraction in the esophageal body and subsequent sphincter closing was seen in 33 of 33 control subjects, 2 of 20 achalasia, and 1 of 13 scleroderma patients (both, p < 0. 001). The observers made the correct diagnosis in 96% of cases. CONCLUSIONS: Achalasia and esophageal scleroderma can be identified by endoscopic observation of motility. This procedure may represent an adjunctive diagnostic test to manometry.

Scintigraphic measurement of regional gastrointestinal transit in the dog.

Scintigraphic techniques can measure sequentially gastric emptying, small bowel transit, and colonic transit in humans, and comparable methods for experimental studies in animals would be useful. We developed such a method in dogs and examined the effects of prokinetic drugs on regional transit. Two isotopes were given to fasting dogs. Polystyrene pellets labeled with 99mTc were mixed in a can of dog food and 111In- labeled pellets were given in a gelatin capsule coated with a pH-sensitive polymer, designed to dissolve in the distal bowel. Gamma camera images were obtained for up to 24 h. Prokinetic drugs were given by intravenous injection. Duplicate baseline studies showed good agreement in seven dogs. In a second group (n = 4), intra- and interanimal variabilities were established. Two novel prokinetic drugs (AU-116 and AU-130) accelerated small bowel and colonic transit. A simple noninvasive method for measuring whole gut transit in dogs was developed and validated. Two new prokinetics accelerated small bowel and colonic transit.

Effects of an irritable bowel syndrome educational class on health-promoting behaviors and symptoms.

OBJECTIVE: The degree to which patient education in the areas of diet, exercise, and stress management can improve symptoms of irritable bowel syndrome (IBS) through healthier lifestyle behaviors is unknown. The aim of this study was to determine the effects of outpatient education on the short and long term outcomes, and the association between health-promoting behaviors and symptoms. METHODS: Pender's Health Promotion Model provided the theoretical framework. The study had a prospective longitudinal design. A consecutive sample of 52 adult outpatients with IBS attended a structured class that taught health-promoting modifications of lifestyle. Participants completed the Health-Promoting Lifestyle Profile (HPLP) and selected items from a Bowel Disease Questionnaire (BDQ) before the class and 1 month and 6 months later. Spearman rank correlations were used to assess the association between HPLP and symptom scores. Wilcoxon rank sum tests compared changes in scores versus their baseline values. RESULTS: Response rates at 1 and 6 months were 75% and 83%, respectively. Results revealed significant 1- and 6 month-improvements in pain and Manning symptoms (p < 0.01) and in some HPLP scores (exercise at 1 month, p < 0.05; stress management at 6 months, p < 0.01). Significant associations were found between some, but not all, HPLP and symptom scores over time. CONCLUSION: A structured IBS educational class for patients with IBS improved symptoms and some health-promoting behaviors. However, relationships among specific behaviors and specific symptoms did not consistently correspond with this improvement.

Eosinophilia and gastrointestinal symptoms after ingestion of shiitake mushrooms.

BACKGROUND: Shiitake mushrooms are a dietary staple in Asia and are increasingly popular worldwide. A cholesterol-lowering study with shiitake showed that 17 of 49 participants withdrew because of rash or abdominal discomfort, and two had marked eosinophilia. One of these latter participants was subsequently challenged for 14 days with shiitake powder and again had eosinophilia. OBJECTIVE: We investigated whether ingestion of shiitake mushroom powder induces eosinophilia or symptoms. METHODS: We studied 10 normal persons. Each participant ingested 4 gm shiitake powder (open label) daily for 10 weeks (trial 1), and the protocol was repeated in these same subjects after 3 to 6 months (trial 2). Blood counts and serum samples were obtained biweekly (trial 1) or weekly along with stool specimens (trial 2). Eosinophil major basic protein and IL-5, IgE, and IgG antishiitake antibodies were measured in sera. Eosinophil-derived neurotoxin was measured in stool extracts. We defined responders as subjects having peak eosinophil counts four or more times their average baseline counts. RESULTS: Each trial had four responders, and trial 2 had one new and three repeat responders. Eosinophilia ranged from 400 to 3900/mm3. Responders had increased blood eosinophils, serum major basic protein, stool eosinophil-derived neurotoxin, and factors that enhanced eosinophil viability. Antishiitake IgE was not detected, and antishiitake IgG increased in two responders. Gastrointestinal symptoms coincided with eosinophilia in two subjects. Symptoms and eosinophilia resolved after discontinuing shiitake ingestion. CONCLUSIONS: Daily ingestion of shiitake mushroom powder in five of 10 healthy persons provoked blood eosinophilia, increased eosinophil granule proteins in serum and stool, and increased gastrointestinal symptoms. Shiitake ingestion suggests a model to study the eosinophil's role in the blood and gastrointestinal tract. Finally, our report raises concerns of possible adverse systemic reactions to this increasingly popular food.