IBD and IBS: are there congruencies?
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Biomedical subjects
Publications and source records attributed to S F Phillips.
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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.
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, P < 0.05). Peripheral alpha 2-adrenergic receptors mediate a net proabsorptive response in the neurally intact canine jejunum in vivo independent of direct central neural effects.
Anorectal function and colonic transit was assessed in 17 severely constipated patients and 15 age-matched controls. The constipated patients were divided into those who had "immobile perineum" (perineal descent < or = 1.0 cm during attempted defecation) and those who had a normal descent (> 1.0 cm) of the perineum. When constipation was accompanied by an immobile perineum, patients had impaired balloon expulsion, impaired and delayed artificial stool expulsion, decreased straightening of the anorectal angle, decreased descent of the pelvic floor with defecation, and prolonged rectosigmoid colon transit compared with the patients with constipation who had a mobile perineum and with normal controls. The mobile-perineum group differed from controls only in colon transit times, having prolonged total colon transit. Anal sphincter resting pressures, immediate artificial stool expulsion, resting anorectal angles, and electromyography of the external anal sphincter and puborectalis did not differentiate the constipated patients from the controls. We concluded that descent of the perineum of < 1 cm was associated with impaired expulsion, an adynamic anorectal angle, and slowed distal colon transit. This simple sign of pelvic floor function distinguished constipated patients with disordered expulsion from constipated patients with normal pelvic floor function. These patients may respond poorly to surgery and conventional management and would therefore be candidates instead for pelvic floor retraining. Accurate characterization and appreciation of pelvic floor dysfunction in patients with severe chronic constipation may improve the selection for and results of surgical and nonsurgical intervention.
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; P > 0.05). In the IPAA patients, regression analysis demonstrated an inverse relationship between stools per day and total SCFA concentration (r = 0.73; P < 0.001). 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 (P > 0.1). 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.
BACKGROUND: Because segmental storage by the colon is relevant to diarrheal states, we quantified colonic transit in 13 healthy volunteers. METHODS: We infused radiolabelled liquids and solids into the cecum. Gamma camera images were obtained for 48 hours and counts measured in ascending (AC), transverse (TC), descending (DC), and rectosigmoid (RS) colons. Bowel movements were scored for consistency and stool outputs of isotopes were quantified. RESULTS: No volunteers developed diarrhea. Times for isotopes to transverse AC and TC were shorter with rapid infusions (P < 0.001). Counts remaining in AC and TC were also correlated with infusion volumes for 9 hours but not thereafter. Solids were initially delayed in AC but solids and liquids were stored equally in TC. Transit through DC was rapid, but RS stored contents for many hours. First appearance of counts in stools and total counts excreted after 48 hours were not dependent on the infusion rate. Fecal consistency and water content correlated significantly with colonic transit times. CONCLUSIONS: Fluids moved ahead of solids in the AC, but liquids and solids were stored equally in the TC. The DC acted mainly as a conduit during fluid overload but the RS stored both isotopes extensively. Stool consistency was a valid reflection of total colonic transit.
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Nonspecific, idiopathic inflammation of ileal pouch mucosa ("pouchitis") after ileal pouch-anal anastomosis is a common complication of this surgical approach. The epithelium of the pouch is ileal, but variable degrees of colonic metaplasia are natural sequelae of construction of such a pouch. One hypothesis is that pouchitis is caused by a deficiency of epithelial nutrition. Thus, a lack of butyric acid (the principal metabolic fuel of colonocytes) or of glutamine (the main fuel of enterocytes) may develop. In this study, our aims were to determine the concentration of total short-chain fatty acids in random stool samples obtained from patients with an ileal pouch-anal anastomosis with and without pouchitis and to test the therapeutic effects of butyrate and glutamine suppositories on pouchitis. During the study, all conventional therapy for pouchitis was discontinued. For 21 days, 9 patients participated in a butyrate trial, and 10 patients were treated with glutamine. Total concentrations of fecal short-chain fatty acids were significantly less in patients with pouchitis than in those without pouchitis. During treatment, 6 of the 10 patients who received glutamine had no recurrence of symptoms, but only 3 of the 9 patients who received butyrate responded similarly. Hence, further studies of glutamine in the treatment of pouchitis seem warranted.
In some patients with the irritable bowel syndrome, rectal urgency and discomfort are major clinical problems and, under experimental conditions, these symptoms are perceived at lesser volumes of rectal distension than they are in asymptomatic controls. Further, a 5-hydroxytryptamine type-3 receptor antagonist increased the threshold for rectal discomfort in irritable bowel syndrome. Our aims were, (a) to measure rectal sensation during isobaric distensions of the rectum, and (b) to test the effect of another selective 5HT3-antagonist, ondansetron 0.15 mg/kg, on rectal sensitivity, colonic tone, rectal tone and manometric responses. Ten healthy volunteers and five patients with diarrhoea-predominant irritable bowel syndrome were studied. A multilumen barostat-manometric assembly was placed in the descending colon, and a second barostat balloon was positioned in the rectum. Tone in the wall of the colon and rectum was measured by the barostat balloon volume during a constant pressure clamp, while intraluminal pressures were recorded by manometry; perceived sensations were also recorded before and after the intravenous administration of ondansetron or placebo in blinded fashion. Rectal resistance to stretch was greater and rectal urgency was induced by lower distending pressures in irritable bowel syndrome, however, basal tone in the rectum was similar in health and irritable bowel syndrome. Ondansetron did not change rectal sensitivity (first sensation or urgency) or tone. Rectal distension did not alter tone in the descending colon or colonic manometry; ondansetron did not influence any index of colonic function.(ABSTRACT TRUNCATED AT 250 WORDS)
Previous observations from our laboratory have suggested that colonic filling from the ileum is characterised by a series of bolus movements. The present experiments were designed to test the hypothesis that bolus transit of ileal contents into the colon would not distinguish between solids and liquids. After a manometric infusion assembly was positioned by mouth into the ileum of 13 healthy volunteers, a mixture of nutrients (75 kcal), incorporating a solid phase radiolabel (111In labeled resin pellets) and a liquid phase marker (99mTc-DTPA), was infused into the ileum. Transit of both labels from the ileum to colon was quantified scintigraphically and ileal motility was also recorded. When markers were infused into the proximal ileum, 100 cm proximal to the ileocolonic junction (six), there were clear cut examples of discriminant transit, when liquids moved more rapidly from the small to the large bowel than did solids. When isotopes were instilled into the distal ileum, less than 50 cm from the ileocolonic junction, no separate transit of the solid and liquid phases was observed. No specific motor pattern of the ileum was regularly associated with bolus filling of the colon. These results support the hypothesis that the distal ileum can discriminate between solids and liquids but that the ileocecal junction cannot.
The aim was to investigate the action of serotonin (5HT) on function of the ileocolonic junction (ICJ) in vivo. In anaesthetised rats, models were developed to study the effects of intra-aortic (ia) serotonin on ileocolonic and colonic transit, and the effects on transit of a number of 5HT receptor antagonists. In the first series of experiments, a bolus of saline labelled with 99mTc DTPA was instilled 20 cm proximal to the ICJ and transit was assessed three hours later by the geometric centre of the spread of isotope. In the second series, similar techniques were used on the postcaecal colon and transit assessed two hours later. In the third series of experiments, the effects of ia 5HT on ileal net fluid flux was evaluated by standard perfusion experiments with 14C polyethylene glycol (PEG) 4000 as a non-absorbable marker in rat plasma-like electrolyte solution. Compared with ia saline, 5HT accelerated ICJ transit significantly (p < 0.05). This acceleration was comparable with the effect of ia bethanechol. The effects of 5HT on ICJ transit were inhibited by the intraperitoneal (ip) infusion of atropine, the 5HT receptor antagonists, methysergide, ketanserin, zacopride, and the 5HT4 agonist, SC53116. Methysergide, zacopride, and SC53116 given with ia 5HT slowed ICJ transit to rates below those of ia saline alone. When these same agents were given together with ia saline, the ICJ transit was not significantly altered. Serotonin, at the dose that accelerated ICJ transit, did not significantly alter colonic transit or ileal fluid transport. In conclusion, 5HT is a potent pharmacological stimulant of transit across the rat ICJ in vivo; the action of 5HT is mediated partly through muscarinic neurones and several 5HT receptor subtypes.
Chronic and/or acute inflammation of the ileal reservoir, so-called "pouchitis", is a frequently observed long-term complication of the ileo-anal "pouch" anastomosis. In ulcerative colitis patients, the prevalence of "pouchitis" varies from less than 10% to higher than 40%. These large variations reflect differences in diagnostic criteria and length of follow-up. The definition of "pouchitis" should include clinical symptoms, macroscopic inflammatory lesions at endoscopy and histological evidence of intense acute inflammation of the reservoir mucosa. Local bacterial overgrowth, lack of short chain fatty acids, increased secondary biliary acids, decreased intraepithelial T-lymphocytes and oxygen derived free-radicals could be implicated in the pathogenesis of pouchitis. In the absence of definite aetiology for pouchitis, its treatment is purely empirical: metronidazole, corticosteroids and 5-aminosalicylic acids are the most used drugs. The long-term consequences of the partial colic metaplasia of the pouch mucosa remain to be elucidated by regular clinical, endoscopical and histological longitudinal.
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.
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.
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.
Mesalamine (5-aminosalicylic acid), a topically administered anti-inflammatory agent, is effective treatment by enema for distal ulcerative colitis; it lacks many of the side effects of orally administered sulfasalazine. In this study, we determined the colonic distribution of a 60-ml mesalamine enema in eight patients (five women and three men, 18 to 48 years old) with active distal ulcerative colitis that ranged from 12 to 40 cm proximal to the anal verge. On 3 consecutive days, each patient self-administered a 4-g (60-ml) 5-aminosalicylic acid enema that contained 3.7 MBq of [99mTc]technetium-sulfur colloid. Anterior and posterior images were obtained at 0, 30, 60, 120, and 240 minutes. During the 4-hour study period, all patients retained the enemas. The enemas spread to the sigmoid region in 24 of 24 studies, to the splenic flexure region in 22 of 24, and to the transverse colon in 1 of 24. Most of the enema was retained in the sigmoid colon. Therefore, we conclude that a 60-ml enema, when administered as recommended clinically, routinely flows retrograde as far as the splenic flexure but rarely spreads beyond this point. These results support the use of intrarectally administered 5-aminosalicylic acid for segmental colitis of the descending colon.