Search

The secretion of carcinoembryonic antigen-like (CEA-like) material into the gastrointestinal tract of 28 fasting normal men was quantified by using intestinal perfusion techniques. CEA-like material was recovered from all levels of the gastrointestinal tract. The highest secretory rate was in the colon (mean +/- SE, 2.41 +/- 2.0 mug/minute per colon), followed by pancreatobiliary secretion and pancreatic secretion. The secretory rate from the stomach, duodenum, jejunum, and ileum was less than 20 ng/minute. After perchloric acid extraction, the CEA-like material from the colon had the same chromatographic and radioimmunologic properties as [125I] CEA. These data suggest that the CEA-like material is normally secreted into the gastrointestinal tract and particularly into the colon.

The human colon can dilate, often to life-threatening proportions. Our aim was to explore nitrergic mechanisms underlying colonic dilation in conscious dogs with enterically isolated ileocolonic loops either extrinsically innervated ( n = 4) or extrinsically denervated ( n= 4). We recorded phasic pressures in ileum and ileocolonic sphincter (ICS), colonic tone, compliance, and relaxation during ileal distension. By NADPH-diaphorase histochemistry, we assessed effects of extrinsic denervation and enteric isolation on nitrergic fibers. Extrinsic denervation increased phasic pressures in ileum, ICS, and colon and abolished ICS and colonic relaxation in response to ileal distension. The nitric oxide synthase (NOS) inhibitor N ω-nitro-l-arginine (l-NNA) increased phasic pressures at all sites and ICS tone but did not abolish colonic relaxation during ileal distension in innervated loops. l-NNA reduced compliance and induced colonic high-amplitude propagated contractions in denervated loops. The NOS substrate donor l-arginine reversed effects ofl-NNA. The number of NADPH-diaphorase fibers increased in both enterically isolated preparations. Nonnitrergic extrinsic nerve pathways mediate reflex colonic relaxation during ileal distension. Enteric isolation augments the number of NOS fibers, an effect not modified by extrinsic denervation.

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.

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).

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.

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. GASTROENTEROLOGY 2000;119:1761-1766

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.

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 persons’ 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.

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

This study evaluated whether twice dailyisotonic perfusion of the bypassed ileum for six weekswould enhance its motor activity and its absorption offluids, electrolytes, and vitamin B12. Thestudy also determined if patients undergoing perfusion hadimproved bowel function and decreased hospital stayafter ileostomy closure. Following proctocolectomy,ileal pouchanal canal anastomosis, and diverting loop ileostomy, six patients self-infused anisotonic solution (sucrose and sodium chloride) into thebypassed ileum twice daily, while seven patients did not(controls). Two months following proctocolectomy, and just prior to ileostomy closure, amanometric catheter assembly was placed into the unuseddistal ileum via the stoma and the distal ileum perfusedwith an isotonic sodium chloride solution for 3 hr during fasting and 3 hr after a meal.Absorption was measured, single and clustered pressurewaves were identified, and a motility index wascalculated. Water absorption, motility index, andcluster parameters did not improve in perfused patients comparedto controls during fasting or after a meal, nor didperfused patients have improved vitamin B12 perfusedpatients also did no better clinically followingileostomy takedown; the onset of bowel movements, theirfrequency, time to tolerate a diet, and hospital staywere similar to controls. We conclude that six weeks oftwice daily isotonic perfusion did not improve motor activity or water, electrolyte, andvitamin B12 absorption in the bypassed distal ileumafter proctocolectomy, ileal pouch-anal canalanastomosis, and loop ileostomy. The perfusion also didnot improve bowel function after ileostomytakedown.

Objective To test the hypothesis that topical administration of pantothenic acid, a precursor of coenzyme A, might result in increased tissue levels of coenzyme A, improvement of fatty acid oxidation, and amelioration of ulcer ative colitis. Material and Methods In an open-label pilot study, three patients with active left-sided ulcerative colitis received nightly enemas that contained 1,000 mg of dexpanthenol for 4 weeks. Before and after the study, patients submitted stool specimens for short-chain fatty acid analysis and urine collections for measurement of pantothenic acid and dicarboxylic acids; they also underwent flexible sigmoidoscopy for procurement of biopsy specimens for histologic examination and measurement of colonic coenzyme A activity. A clinical disease activity index and histologic disease activity index were used to assess response. Results Despite increases in urinary pantothenic acid, no significant changes were found in colonic tissue coenzyme A concentrations, fecal short-chain fatty acid concentrations, or urinary dicarboxylic acid concentrations. Moreover, no significant changes in clinical or histologic disease activity were noted. Although stool frequency and rectal bleeding remained unchanged, all patients noted increased abdominal cramping, and one patient had an increased extent of disease. Results Despite increases in urinary pantothenic acid, no significant changes were found in colonic tissue coenzyme A concentrations, fecal short-chain fatty acid concentrations, or urinary dicarboxylic acid concentrations. Moreover, no significant changes in clinical or histologic disease activity were noted. Although stool frequency and rectal bleeding remained unchanged, all patients noted increased abdominal cramping, and one patient had an increased extent of disease. Conclusion Topically administered dexpanthenol seems to be absorbed, but at the dose used in this study, it did not influence concentrations of co-Ionic coenzyme A activity, fecal short-chain fatty acids, or clinical response in patients with active left-sided ulcerative colitis.

To analyze our experience in patients with chronic diarrhea by using a noninvasive transit study that measures gastric emptying as well as small bowel and colonic transit.Results from 94 consecutive transit tests, for which diarrhea was the main indication, were reviewed and correlated with the final classification of patients as having an organic or nonorganic disorder.Sixty patients were considered to have a nonorganic cause of diarrhea, of whom 15 had previously undergone cholecystectomy. The other 34 patients were considered to have diarrhea on the basis of an organic diagnosis. Gastric emptying was more often rapid in patients with a nonorganic cause (P0.05), but not if cholecystectomy had been performed previously. Small bowel transit was fast more often in patients with organic diarrhea than in those with no organic cause of the diarrhea (P0.05); colonic transits showed no significant differences among groups.The findings implicate a motor abnormality of the upper gut, rapid gastric emptying, as a pathophysiologic mechanism of functional bowel disorders with diarrhea. The results imply that additional prospective observations should be worth-while.

The aim of this study was to compare in vitro various methods for recording intestinal sensitivity and compliance. Relationships between volume and pressure were determined in segments of penrose tubing and pig gut ("artificial intestine') using pressure increments of 2 mmHg (0-24 mmHg). We tested two direct methods of distension of the entire segments (by syringe inflation and the Mayo barostat); we also used three different balloon devices for indirect distension (a 10 cm polyethylene barostat bag, a 10 cm latex condom balloon and a 6 cm latex condom balloon). Maximal distending diameters of the recording systems were measured by injecting from 0 to 160 mL of air. The elastic properties of the balloons were also tested by distensions in air and in rigid tubes. All recording systems accurately detected a lesser compliance of the penrose drain as compared to pig gut. In absolute terms, only the compliance measured with a polyethylene barostat bag distended with a syringe was not different from the compliance of the segment as measured directly. The bellows of our barostat and the latex balloons had significant intrinsic compliances which interfered with the recorded pressure-volume curves. On the other hand, highly compliant plastic bags recorded most faithfully the compliance of artificial gut and that of non-compliant rigid tubes. For comparable volumes of distension, external diameters were larger with the 6 cm latex balloon than with the 10 cm latex balloon or the 10 cm polyethylene barostat balloon. A polyethylene bag distended with a non-compliant air injector (syringe) reflected most accurately the pressure-volume relationships of tubular structures. The different maximal diameters assumed by the three distending devices may explain, in part, why lower volumes of distension are required to elicit symptoms with smaller distending balloons in vivo.

Being the final pathway for chyme and digestive residues, the colorectum influences bowel function critically. The most important and relevant symptoms of colonic dysfunction are diarrhea, constipation, urgency, and pain. Despite the effects of many investigators, over several decades, the motor physiology of the human colon is still relatively obscure. Most is known about patterns of colonic transit. In practice, measurements of transit are the best characterized and most widely available tests of colonic motor function. Colonic hypersensitivity, implying an abnormality of afferent signaling, is assuming greater importance in the pathophysiology of conditions as common as IBS and inflammatory bowel disease.

To explore mechanisms whereby unabsorbed nutrients in the ileum inhibit the upper gut ("ileal brake"), we perfused the canine ileum or colon and monitored phase 3 in the duodenum. Fasting motility was recorded when the ileum or colon was perfused with 154 mM NaCl, a mixed isotonic nutrient solution (Ensure), or individual nutrients (maltose, casein hydrolysates, or sodium oleate). Blood samples were collected before and during the perfusions. The ileum was also perfused with 154 mM NaCl while peptide YY (PYY) was infused by vein. In both sets of experiments, plasma levels of PYY, neurotensin, and glucagon-like peptide-1 (GLP-1) were measured. Ileal or colonic perfusion of Ensure delayed phase 3 [migrating motor complexes (MMC)] in the duodenum, inhibited ileal motility, and increased plasma levels of PYY and GLP-1. Ileal casein and oleate and colonic casein also delayed the duodenal MMC. The MMC cycle length and plasma levels of PYY were closely correlated. Intravenous PYY prolonged the MMC cycle; an intravenous dose of 100 pmol.kg-1.h-1 of PYY mimicked the effects of ileal Ensure. These results support the hypothesis that PYY, and possibly GLP-1, participate in the ileal brake. This negative feedback loop also affects the distal small bowel. The proximal colon also triggers the feedback inhibition of gut motility (colonic brake).

The cardinal symptoms of IBS are abdominal pain and either diarrhea or constipation. Two cases with very different presentations illustrate a simplified diagnostic workup and provide practical suggestions for management. Patients can expect substantial benefits from treatment, provided they are willing to participate in its execution.

Objective To describe an initial clinical experience with a nontnvasive scintigraphic technique for assessing gastrointestinal motility. Design We studied gastric, small bowel, and colonic transit in 109 undetected patients encountered between June and December 1992 at the Mayo Clinic. Material and Methods The study patients were categorized on the basis of major complaint (constipation in 46, upper gastrointestinal symptoms in 45, and diarrhea in 18) and presence or absence of an underlying organic disease. Radioscintigraphy was used to analyze various regions of the gastrointestinal tract; scans were obtained at 2, 4, 6, and 24 hours after ingest ion of a radiolabeled test meal. Results Overall, patients with a main complaint of constipation usually had slow or normal gastric, small bowel, and colonic transit, whereas those with diarrhea as the major symptom usually had normal or fast results of these studies. In the 65 patients with no underlying organic disease, inconsistent patterns of gastric emptying and small bowel and colonic transit were noted. Conclusion Our results suggest that this 24-hour scintigraphic test may be clinically useful in screening for dysmotility syndromes in patients with nausea, vomiting, diarrhea, or constipation.

We aimed to record fundic motor activity in man using the barostat to ascertain if fundic motility is affected by rectal distension. The distal ends of two barostat tubes were placed in the gastric fundus and rectum in 10 healthy volunteers. The gastric bag was first inflated to a constant pressure level that recorded phasic motor activity as changes in volume of the air-filled bag. Baseline motor activity was recorded before, during, and after a 15-min period of constant rectal distension that was clearly perceived by all subjects but was not painful. In all subjects, continuous phasic volume changes, reflecting fundic motor activity, were recorded at a rate of 1-3/min. During rectal distension, a consistent change in mean contractile force of these phasic volume events was not detected; a decrease of more than 30% occurred in only three subjects. We conclude that fundic phasic volume changes are recordable by the barostat, but these are not substantially inhibited by rectal distension.

Background/Aims: Reflex relaxation is a mechanism whereby the colon can show short-term dilatation in the absence of mechanical obstruction. This study investigated the tonic response of the canine colon to ileal distention and its pharmacological control. Methods: In four dogs, the tone of the proximal colon was recorded by a barostat during distention of the terminal ileum. Results: Ileal distention inhibited ileal motility and relaxed the colon. Adrenergic blockade by propranolol plus phentolamine, nicotinic blockade by hexamethonium, and the nitric oxide synthase inhibitor N gw -nitro-l-arginine methylester significantly increased resting tone of the colon but did not inhibit relaxation induced by ileal distention. Muscarinic blockade by atropine completely relaxed the colon, and no further decrease in tone was observed after ileal distention. The neurokinin 2 antagonist SR48968 did not alter colonic tone. Conclusions: The barostat was able to monitor resting tone of the canine colon, which was shown to be under inhibitory control by adrenergic, cholinergic-nicotinic, and nitric oxide-like transmitters. Inhibition of colonic tone by ileal distention was not mediated solely by adrenergic, cholinergic-nicotinic, or nitric oxide mechanisms. Reflex relaxation, possibly predisposing to acute colonic dilatation, may be activated by multiple mechanisms that may differ from those controlling resting tone.

Although alpha 2-adrenergic agonists stimulate absorption in the mammalian small and large intestine in vitro, the possibility of central neural effects have confounded interpretation of in vivo studies. Our aim was to assess the effects of intravenous administration of alpha-methylnorepinephrine (MNE), an alpha 2-adrenergic agonist that does not cross the blood-brain barrier, on net jejunal absorption of water and electrolytes in the neurally intact, conscious dog. Absorption from a 30-cm proximal jejunal segment was studied using a triple-lumen perfusion technique in seven dogs. A warmed, isosmolar, balanced electrolyte solution containing [14C]polyethylene glycol was infused at 5 ml/min. Net jejunal fluxes of water and electrolytes were determined before, during, and after a 1.5-hr infusion of MNE (900 nmol/kg/hr). MNE increased net jejunal water absorption (from 12.9 +/- 1.8 to 22.5 +/- 1.5 microliters/cm/min, P0.05). Peripheral alpha 2-adrenergic receptors mediate a net proabsorptive response in the neurally intact canine jejunum in vivo independent of direct central neural effects.

Olestra, the name proposed for the mixture of hexa-, hepta- and octaesters of sucrose and long-chain fatty acids, is a nondigestible, nonabsorbable lipid with physical properties and taste that are similar to those of natural triglycerides. Our aim was to determine whether substitution with up to 30 g of olestra in a 45-g fat meal would alter gastric, small bowel, and colonic transit. Five groups, each of six healthy volunteers, ingested 800-kcal, 22-g protein meals containing a total of 45 g of lipid (N = 24) or 15 g of lipid (N = 6). Among those receiving the 45-g fat meal, 0, 7.5, 15 and 30 g of lipid were substituted with olestra (N = 6 per group). The 15-g fat meal consisted entirely of natural triglyceride. A dual gamma camera scintigraphic method was used to estimate gastric and small bowel transit (99mTc pellets in the meal) and colonic transit (111In pellets). The latter was achieved by the delayed release of 111In pellets from a capsule coated with a pH-sensitive polymer, methacrylate, that disintegrated in the terminal ileum. There were no differences in the gastric, small bowel, or colonic transits of any of the five equicaloric meals. Some individuals had a significantly greater 48-hr stool weight after ingesting 15 g of olestra, but stool weights of subjects consuming 7.5 g or 30 g of olestra did not differ from controls. We conclude that substitution with olestra of up to 30 g in a 45-g fat meal does not significantly alter gastrointestinal transit in healthy subjects.

Random stool samples were obtained from 14 ileal pouch-anal anastomosis (IPAA) patients 43 +/- 5 (mean +/- SEM) months after surgery, and the concentrations of individual short-chain fatty acids (SCFAs) were determined by gas liquid chromatography. Stool frequency was determined from a diary recorded for 15 days prior to stool sampling. The frequency, amplitude, and duration of phasic contractions (PCs) within the pouch following infusion of a physiologic concentration of SCFAs and normal saline randomly into the pouch of six IPAA patients were determined manometrically. The mean total SCFA concentration after IPAA did not differ significantly from normal stools (83 +/- 20 mM after IPAA vs. 97 +/- 10 mM for controls; P0.05). In the IPAA patients, regression analysis demonstrated an inverse relationship between stools per day and total SCFA concentration (r = 0.73; P0.001). Moreover, no change in frequency (3.0 +/- 0.9 vs. 3.2 +/- 0.8 PCs/30 minutes), amplitude (26 +/- 5 vs. 25 +/- 4 mmHg), or duration (23 +/- 3 vs. 26 +/- 2 seconds) of PCs was found after SCFA infusion compared with saline control (P0.1). These findings demonstrate that SCFAs are present in ileal pouch effluent and that stool frequency may be related to fecal SCFA concentration. Also, the normal contractile response of the terminal ileum to SCFAs does not occur in the ileal pouch.

The role of the human ileocolonic junction in the transit of solid contents through the entire gut was evaluated. Eight patients, well compensated after right hemicolectomy for localized colon cancer, and eight age-matched healthy controls were enrolled. Scintigraphic transit was quantified after subjects ingested a mixed meal containing 111In-labeled Amberlite beads (average diameter, 1 mm; Sigma Chemical Co., St. Louis, MO). Gastric emptying was initially faster in the postoperative group, but overall emptying was not different from controls; small bowel transit also did not differ between the groups. In patients in whom the distal ileum, ileocolonic sphincter, and proximal colon were absent, isotopes moved from small to large bowel in a manner that was qualitatively and quantitatively no different from that of controls. Major episodes of coloileal reflux could not be identified in either group. After hemicolectomy, the residual transverse colon, and to a lesser degree the descending colon, were able to store solid residue, although in lesser amounts than the unoperated large bowel. The ileocolonic sphincter in humans appears to play only a minor role, at most, in ileocolonic transit, and the colon remaining after right hemicolectomy stores residue so that bowel habits are not greatly disturbed.

Serotoninergic innervation may contribute to the control of colonic motility and to visceral sensation from the large bowel. Indeed, ondansetron hydrochloride, a selective 5-hydroxytryptamine type 3 receptor antagonist, has been shown to slow colonic transit in healthy volunteers. Thus, we wished to determine whether 5-hydroxytryptamine type 3 receptor blockade slows colonic and small bowel transit in patients with diarrhea-predominant irritable bowel syndrome (IBS) and whether symptoms would be ameliorated with drug therapy. Of 14 patients with well-established IBS who entered a randomized, double-blind, placebo-controlled crossover pilot trial of 4 weeks of treatment with ondansetron, 16 mg three times daily, 11 completed the study. A minimal "washout period" of 4 weeks (median, 7 weeks) separated the two phases of the trial because patients were required to have similar symptoms before both periods of the study. Colonic transit tended to be longer during drug therapy than during the placebo trial, but this difference was not significant. Small intestinal transit and orocecal transit were unchanged by the drug. The integrated and peak postprandial increases in neurotensin, peptide YY, and human pancreatic polypeptide in serum were not significantly different in the drug and placebo periods. After treatment with ondansetron, stool consistency improved significantly; however, stool frequency, stool weight, abdominal pain, and the symptom criteria for IBS were not significantly altered by the drug. The results of this pilot study suggest that the motor effects expected with 5-hydroxytryptamine type 3 receptor blockade (namely, slowed colonic transit) may be diminished in some patients with IBS. The subjective improvement in stool consistency may reflect changes in the perception of defecation. Therefore, 5-hydroxytryptamine type 3 receptor blockade warrants further study in diarrhea-predominant IBS.

Transient mucosal ischemia may cause oxygen-derived free radical production by xanthine oxidase, precipitating pouchitis after ileal pouch-anal anastomosis. Our aim, therefore, was to determine the effect of allopurinol, a xanthine oxidase inhibitor, in patients with acute and chronic pouchitis. Acute pouchitis was characterized clinically by sporadic episodes of increased frequency and decreased viscosity of stools, hematochezia, fever, malaise, and pelvic pain, which resolved promptly with treatment. Chronic pouchitis patients required continuous treatment to remain asymptomatic and invariably developed the signs and symptoms of pouchitis within one week following cessation of therapy. Eight patients with acute pouchitis were treated with allopurinol (300 mg p.o. b.i.d.) during the episode. Fourteen patients with chronic pouchitis had their standard antibiotic therapy discontinued while still asymptomatic; they were then given allopurinol (300 mg p.o. b.i.d.) for 28 days. Acute pouchitis resolved promptly in four of eight patients. Seven of the 14 patients with chronic pouchitis responded completely with no recurrence of symptoms during treatment. Allopurinol either terminated an episode of acute pouchitis or prevented pouchitis from recurring in 50 percent of patients. These data support a role for mucosal ischemia and oxygen free radical production in the etiology of pouchitis.

Human colonic muscle tone varies diurnally and postprandially in predictable ways. Increased tone reduces the capacity of the colon to store contents after a meal, whereas increased distensibility (lesser tone) during sleep enlarges the storage capabilities and may slow transit. We tested the hypothesis that antidiarrhoeal drugs would also alter tone which, in turn, might reduce diarrhoea by facilitating the storage and salvage of fluids. Using a colonic barostat to create low pressure, isobaric colonic distension in healthy volunteers, we found that intravenous atropine (0.01 mg/kg) relaxed the colon during fasting, reduced the postprandial increase in tone, and enhanced relaxation in the late (1-2 hour) postprandial period. Intravenous morphine (0.1 mg/kg) caused variable effects soon after injection but, in fasting subjects, the descending colon relaxed 70-90 minutes after morphine. These changes in colonic motility were not always obvious by conventional manometric recording. Colonic distensibility is increased by antidiarrhoeal drugs and this effect may contribute to their efficacy in slowing colonic transit and augmenting absorption.

The inherent variability of symptoms and motor abnormalities in patients with the irritable bowel syndrome has hampered the demonstration of motor abnormalities that could underlie symptoms. The aim in the current study was to evaluate whether altered regional capacitance or transit of solid residue through the unprepared human gut were factors in the diarrhea of patients with the irritable bowel syndrome. In 10 such patients and in 5 healthy controls, gastric and small bowel transits were evaluated scintigraphically by means of a mixed meal containing 99mTc-labeled resin pellets. Regional colonic transit was quantitated by 111In-labeled pellets delivered to the ileocecal region by a pH-sensitive, methacrylate-coated capsule. Symptomatic patients did not have significantly altered gastric or small bowel transits, but colonic transit was accelerated in 7 of 10 persons with the irritable bowel syndrome (P less than 0.02), in the proximal colon of five patients and in the left colon of two patients. The 24-hour stool weight was positively correlated with the rate at which solid residue emptied from the ascending and transverse colons (r = 0.78; P less than 0.01). There was also an inverse relationship between emptying rates and maximal volumes accommodated by the proximal colon (r = -0.58; P less than 0.05), although the maximum volume of the proximal colon was not significantly different in patients and healthy subjects. Thus, accelerated transit through the proximal colon is a factor in the pathophysiology of the irritable bowel syndrome and influences the stool weight of such patients. The capacitance of the proximal colon presumably influences its storage capacity and, hence, the rate at which it empties.

The aim was to determine the effect of intraluminal acetic acid and proximal colonic distension on canine ileocolonic sphincter pressure, ileal motility, and coloileal reflux. In six conscious dogs with an isolated ileocolonic loop, basal pressure of the ileocolonic sphincter was similar during ileal perfusion with 100 mM acetic acid at 1 ml/min (mean +/- SEM = 18 +/- 0.4 mm Hg) and with saline (18 +/- 0.5 mm Hg; P = 0.81). Discrete clustered ileal contractions were more frequent with acetic acid, however, and when they propagated across the sphincter, sphincter pressure increased from 18 +/- 0.4 mm Hg to 36 +/- 1.3 mm Hg (P = 0.002). Sphincter pressure was also greater during colonic perfusion with acetic acid (32 +/- 0.7 mm Hg) than during ileal perfusion with acetic acid or saline (P less than 0.017). Moreover, sphincter pressure gradually increased as the colon was distended with saline (slope = 0.8 mm Hg/cm H2O, P less than 0.017) or acetic acid (slope = 0.5 mm Hg/cm H2O, P less than 0.017), but the increase did not prevent coloileal reflux. In conclusion, ileal clustered contractions, colonic perfusion of acetic acid, and colonic distension all increased canine ileocolonic sphincter pressure.

Greater understanding of the physiology of the ICJ allows exploration of how these mechanisms are deranged in disease processes. Studies must be expanded to different subgroups of patients with IBS to learn more of the pharmacologic control of these functions, and to integrate motor, transit, secretory, and absorptive functions. Lying at the gateway between the predominantly absorptive regions of the small intestine and the storage and excretory regions of the colon, the ICJ may be important in the pathophysiology of pain, bloating, and altered bowel movements in patients with IBS.

We sought to determine whether the proximal colon modifies its capacity to accommodate contents by altering the tone within its wall. In dogs equipped with manometric recorders in the terminal ileum and proximal colon, a highly compliant bag was introduced into the proximal colon. With the use of an electromechanical barostat, the capacity of the colonic segment was monitored at a constant low-distending pressure; the volume of air required to maintain a preset pressure in the bag was recorded by the barostat. During fasting, rhythmic cycles of volume were recorded, with a cycle frequency of approximately 1/min. Importantly, this phenomenon was not related to the simultaneous recording of manometric pressures in the adjacent bowel or to the interdigestive cycle (phase III) in the ileum. Peristaltic-like pressure complexes (recorded manometrically) in the ileocolonic region were associated with receptive relaxation of the proximal colon. Feeding, bethanechol, and morphine reduced volumes accommodated in the bag, presumably by increasing tone in the wall of the colon. Atropine had the opposite effect. These results support the concept that tonic changes in the wall of the proximal colon, which could influence accommodation and storage in the large bowel, are not always recorded by conventional techniques.

Helicobacter pylori colonization of the gastric mucosa is strongly associated with chronic nonspecific gastritis; moreover, there is evidence to suggest that H. pylori may cause this form of gastritis. However, there is little or no information on the prevalence of H. pylori in specific forms of gastritis. Our hypothesis was that if H. pylori was pathogenic in chronic nonspecific gastritis, organisms would be found frequently in this type of gastritis but infrequently in specific forms of gastritis. Prevalence rates of H. pylori were determined independently in patients with eosinophilic and Crohn's gastritis, Menetrier's disease, and chronic nonspecific gastritis. The prevalence of H. pylori in patients with chronic nonspecific gastritis was 71%, whereas the organism was not identified in patients with any form of specific gastritis. This finding further supports the accumulating evidence that H. pylori is a primary pathogenic factor in chronic nonspecific gastritis.

In five healthy male volunteers, we compared solid and liquid transit though the unprepared colon. 99mTc-diethylenetriaminepentaacetic acid in 10 ml saline was injected into the cecum through an orocecal tube at 1 ml/min immediately after a methacrylate-coated medication capsule was seen to deliver 111In-labeled Amberlite IR-120PLUS pellets (avg diam, 1.0 mm) into the cecum. Segmental transits through the ascending, transverse, descending, and rectosigmoid regions were determined using a dual gamma camera system and a variable region of interest program. There was no difference between solid [half time, 247 +/- 60 (SE) min] and liquid (312 +/- 88 min) emptying from the ascending colon. Colonic transit of solids and liquids was further compared by regional counts and stool outputs at 12 and 24 h. There were no significant differences between solids and liquids (P greater than 0.05). Our data suggest that transit through the unprepared human colon is not different for solids and small volumes of liquids, when these are delivered together to the ascending colon.

We describe here further observations on a novel motor phenomenon that can be recorded regularly from the canine ileum in the late postprandial period, i.e., when residue of a meal reaches the distal small bowel. We reported before that this unique pattern of motility consisted of intraluminal pressure waves at a frequency (20-24/min) much greater than that of the ileal slow wave. In the current experiments, we document that these intraluminal pressure waves coincide with contraction of the circular muscle layer, as recorded from serosal strain gauges. However, the cellular origin and propagation of these contractile events are still unclear. By studying dogs with ileal loops and those with an intact bowel, we conclude that this is a local response of the ileum to the arrival of nutrients in its lumen and that it is under cholinergic control. This report supports the concept that the ileum may be particularly sensitive to its local intraluminal environment.

The aims of this study were to assess gastric emptying, small bowel transit and colonic filling in patients with motility disorders, with particular attention to the patterns of colonic filling. Gastrointestinal transit was assessed using a previously validated radiolabeled mixed meal. Fourteen patients with clinical and manometric features of chronic intestinal pseudoobstruction & classified as intestinal neuropathy and 6 as intestinal myopathy, were studied. The results were compared with those from 10 healthy controls studied similarly. Gastric emptying and small bowel transit of solids were significantly slower in both groups of patients than in healthy controls (P less than 0.05). In health, the ileocolonic transit of solid chyme was characterized by intermittent bolus transfers. The mean size of boluses transferred to the colon (expressed as a percentage of ingested radiolabel) was significantly less (P less than 0.05) in patients with intestinal myopathy (10% +/- 4% (SEM)] than in healthy controls (25% +/- 4%) or in patients with intestinal neuropathy (25% +/- 4%). The intervals between bolus transfer of solids (plateaus in the colonic filling curve) were longer (P less than 0.05) in myopathies (212 +/- 89 minutes) than in health (45 +/- 7 minutes) or neuropathies (53 +/- 11 minutes). Thus, gastric emptying and small bowel transit were delayed in small bowel neuropathies and myopathies. Bolus filling of the colon was less frequent and less effective in patients with myopathic intestinal pseudoobstruction, whereas bolus transfer was preserved in patients with neuropathic intestinal pseudoobstruction.

We used a noninvasive method to label the solid phase of contents in the unprepared human colon. 111In-labeled Amberlite pellets (0.5-1.8 mm diam) were placed in a gelatin capsule that was then coated with a pH-sensitive polymer (methacrylate). In vitro, the capsules disintegrated in simulated small bowel contents within 1-2 h; when ingested by healthy subjects, capsules released radiolabel in the distal ileum or proximal colon in 13 of 15 subjects. Transit of 111In-pellets through the unprepared colon could then be quantitated radioscintigraphically. Segmental transit was defined in the ascending (AC), transverse (TC), descending (DC), and rectosigmoid (RS) colon. Radioactivity was also quantitated in stools. At 12 h, radioactivity was most obvious in the AC (59 +/- 11%, mean +/- SE) and the TC (21 +/- 6%); at 24 h, counts were distributed equally between AC, TC, and stools (P greater than 0.05); by 48 h, 56 +/- 11% counts had been excreted, although 30 +/- 10% remained in the TC. At 24 and 48 h, the amount in DC or RS was lower (P less than 0.05) than in the TC or in stools. Emptying of the AC was characterized by an initial lag period, when no counts emptied into the TC, followed by a period of emptying that was approximately linear. Thus this simple approach is able to label contents in the healthy human colon. The ascending and transverse colon appear to be sites of storage of solid residue, whereas the left colon and rectosigmoid function mainly as conduits.

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 M3antagonist) delayed gastric emptying and colonic transit, the selective M1and M2muscarinic 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. M3receptors are important in the control of gastric emptying and colonic transit, and NOS inhibition slowed small bowel and colonic transit.

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).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.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 (p0.0001). Scores for both eosinophil infiltration and degranulation were also significantly higher in the CC group compared to controls (p0.0001). 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.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.

Megacolon refers to cecal dilatation above the dimension of 12 cm and above 6.5 cm of the sigmoid colon, measured at the pelvic brim. Dilatation of the colon can be broadly categorized into three clinical entities: In acute megacolon (Ogilvie's syndrome), colonic dilatation is attributed to a sympathetically mediated reflex response to a number of serious medical or surgical conditions in elderly patients. The initial tasks are to exclude mechanical obstruction (with a hypaque enema), to discontinue enabling medications, and to correct metabolic disturbances. Dilatation of the cecum to greater than 12 cm diameter is a cause for grave concern. The rectum should be decompressed with an indwelling tube and tap water enemas. Intravenous neostigmine is generally effective and safe for patients with colonic distention unresponsive to such conservative therapies. Endoscopic decompression is necessary for patients who do not respond to, or relapse after neostigmine, or in whom neostigmine is contraindicated. Signs of peritonitis may imply colonic perforation, and surgery will be needed, often on an emergent basis. Toxic megacolon is secondary to an identifiable inflammation of the colon. Therapy is directed toward specific treatment for the underlying disorder, inflammatory bowel disease, or infectious colitis. Bowel rest and close monitoring of the clinical status is vital. Colectomy may be needed under emergency circumstances. Chronic megacolon may be congenital (due to Hirschsprung's disease) or may represent the end-stage of any form of refractory constipation (slow transit constipation or pelvic floor dysfunction). The initial treatment for Hirschsprung's disease is surgery, while pelvic floor dysfunction and encopresis respond to biofeedback therapy. In chronic idiopathic megacolon, medical measures, such as colonic evacuation with enemas, fiber supplementation, and laxatives may suffice. If severe motor dysfunction is confined to the colon, a subtotal colectomy with an ileorectal anastomosis, or an ileostomy may occasionally be necessary.

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.

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.

Esophageal motility disorders are usually diagnosed by manometry. We evaluated videoendoscopy as a diagnostic test.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.In the mid esophagus at 25 cm, lumen-occluding peristaltic contractions were identified in 26 of 33 control subjects versus 1 of 20 achalasia (p0.001) and 3 of 13 scleroderma patients (p0.005). As viewed in the lower esophagus, the lower esophageal sphincter opened normally in 31 of 33 control subjects versus 1 of 20 achalasia (p0.001). In scleroderma, the sphincter never closed in 12 of 13 patients (p0. 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, p0. 001). The observers made the correct diagnosis in 96% of cases.Achalasia and esophageal scleroderma can be identified by endoscopic observation of motility. This procedure may represent an adjunctive diagnostic test to manometry.

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 with99mTc were mixed in a can of dog food and111In- 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.

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/mm 3 . 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.(J Allergy Clin Immunol 1998;101:613-20.)