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Biomedical subjects

S F Phillips

Publications and source records attributed to S F Phillips.

At least 55 records · Page 3Linked to original sources

Motility and tone of the left colon in constipation: a role in clinical practice?

OBJECTIVES: Colonic motor mechanisms deranged in constipation are not understood completely. Our aim was to measure left colonic motility and tone, during fasting and postprandially in patients with chronic constipation. METHODS: During 1 h fasting and 2 h postprandially, we measured pressures (multilumen manometry) and tone (barostat) in the left colon of 15 healthy controls and 40 patients with chronic constipation associated with slow (n = 15) or normal colonic transit (n = 12) or outlet obstruction (n = 13). RESULTS: Fasting tone was similar in all groups, and all demonstrated a significant increase in motor activity to food. There was lower postprandial tone (p < 0.05) in the slow transit and outlet obstruction groups. There were no differences in the timing of the tonic response or the number or amplitude of high-pressure propagated contractions. The slow transit group had lower postprandial phasic responses in the rectosigmoid (p < 0.05) and descending (p < 0.1) colon; the outlet obstruction group had lesser descending (p < 0.05) and rectosigmoid (p < 0.1) colon phasic motility. CONCLUSIONS: Colonic intraluminal measurements alone do not discriminate subgroups of chronic constipation more accurately than transit and pelvic floor tests, and currently have a limited role in clinical practice. However, manometry and tone measurements may be helpful in confirming a diagnosis of slow transit constipation (colonic inertia) in patients considered candidates for surgical treatment.

Adolescent↗

The diverse spectrum of irritable bowel syndrome.

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.

Adult↗

Pouchitis--a poorly understood entity.

Pouchitis is an increasing drawback to patients who undergo ileal pouch-anal anastomosis for ulcerative colitis; complication overshadows the overall good functional results of this sphincter-saving operation. There is a need for cooperative, multicenter, and longitudinal studies of patients undergoing ileal pouch-anal anastomosis, to unravel the etiology and pathophysiology of pouchitis. Because of the absence of a mucosal inflammation before pouch construction, patients operated on for familial adenomatous polyposis are the perfect control group. Thus, it may be possible to elucidate and define the sequence that leads to pouchitis, including overgrowth of a colonic type flora, transformation of the histology to an epithelium with colonic features, an altered biochemical milieu in the lumen (volatile fatty acids, secondary bile acids), and changes in mucosal defense mechanisms.

Anal Canal↗

Visceral perception in irritable bowel syndrome. Rectal and gastric responses to distension and serotonin type 3 antagonism.

We wished to determine if visceral perception in the rectum and stomach is altered in patients with irritable bowel syndrome and to evaluate the effects on visceral sensation of 5-HT3 receptor blockade. Twelve community patients with diarrhea-predominant irritable bowel syndrome and 10 healthy controls were studied in a double-blind, randomized, placebo-controlled study. Using two barostats, the stomach and rectum were distended, with pressure increments of 4 mm Hg, from 10 to 26 mm Hg; visceral perception was measured on an ordinal scale of 0-10. Personality traits were measured using standard psychological methods, and somatic pain was evaluated by immersion of the nondominant hand in cold water. The effect of 5-HT3 antagonism was tested with a single intravenous dose of ondansetron at 0.15 mg/kg. Gastric perception was higher in irritable bowel syndrome, but rectal distension was perceived similarly in irritable bowel syndrome and controls. Pain tolerance to cold water was also similar in irritable bowel syndrome and controls. Ondansetron induced rectal relaxation and increased rectal compliance but did not significantly alter gastric compliance or visceral perception. Psychological test scores were similar in patients and controls. We conclude that in this group of psychologically normal patients with irritable bowel syndrome, who were not chronic health-care seekers, visceral perception was normal. Ondansetron did not alter gut perception in health or in irritable bowel syndrome.

Adult↗

Fecal bile acids, short-chain fatty acids, and bacteria after ileal pouch-anal anastomosis do not differ in patients with pouchitis.

Construction of an ileal reservoir changes the fecal bacterial flora and the fecal composition of bile acids and short-chain fatty acids. We examined the relationships between pouch inflammation (pouchitis) and pouch content, as assessed by analysis of fecal bacteria, bile acids, and short chain fatty acids. Four groups were studied: ileal pouch-anal anastomosis (IPAA) for ulcerative colitis with pouchitis (N = 10), IPAA without pouchitis (N =5), IPAA for familial adenomatous polyposis without pouchitis (N = 5); and Brooke ileostomy for ulcerative colitis, which served as controls (N = 5). Pouchitis was defined as > or = 7 points on an 18-point pouchitis disease activity index. Aerobic and anaerobic bacteria were quantitatively cultured. Total aqueous-phase bile acids were measured by thin-layer chromatography and an enzymatic 3 alpha-OH hydroxysteroid dehydrogenase method. Fecal short chain fatty acids were measured by gas liquid chromatography. All patients with an IPAA had higher ratios of anaerobes/aerobes and concentrations of anaerobic gram-negative rods than did patients with an ileostomy. There were no other differences between patient groups with respect to bacteria, aqueous-phase total bile acids, or fecal short-chain fatty acids. Fecal concentrations of bacteria, bile acids, and short-chain fatty acids were similar in patients with and without pouchitis, indicating that these factors can not be the sole cause of pouchitis.

Adenomatous Polyposis Coli↗

Tonic responses of canine proximal colon: effects of eating, nutrients, and simulated diarrhea.

Our hypothesis was that the proximal colon relaxes to accommodate flow from the ileum. Therefore, we recorded tonic responses of the canine proximal colon to flow through the ileum and colon stimulated by 1) an 840-kcal meal, 2) nutrients perfused into the ileum and colon, or 3) rapid infusion of saline into the ileum with overflow into the colon. Saline infusion was considered to be a model of diarrhea, and the effects of an antidiarrheal (morphine sulfate) were therefore assessed. Proximal colonic tone was measured with a barostat. Tone increased before and after the arrival of chyme in the ileocolonic region. Perfusion of nutrients into the ileum and colon also significantly increased (P < 0.05) colonic tone compared with equal volumes of saline. Rapid perfusion of the ileocolonic segment with saline increased colonic tone; this increase was significantly greater (P < 0.01) when preceded by morphine. In contrast to our hypothesis, tone of the canine proximal colon increased in response to ileal flow. The increase in colonic tone during the late response to food was at least partly attributable to stimulation by intraluminal contents.

Animal Nutritional Physiological Phenomena↗

Effects of ethanol, xylose, and glucose on canine jejunal motility.

Ethanol is an important source of calories that can cause certain gastrointestinal symptoms, notably diarrhea. To examine the effects of ethanol on the small bowel, we intraluminally perfused the jejunum of four dogs with ethanol (18, 9, 4.5, and 1.5%, wt/vol), D-xylose (30, 15, 7.5, and 4.5%, wt/vol), or glucose (30 and 5%, wt/vol). In other experiments, these solutes were infused intravenously. Saline was always given by the alternate route; jejunal manometry was recorded during and after the infusions. Phase III of the interdigestive cycle was delayed by all intraluminal infusions except for 4.5 and 1.5% ethanol, 4.5% xylose, and 5% glucose. In addition, the onset of irregular contractile activity was delayed more with intraluminal ethanol than with intraluminal xylose or intraluminal glucose (P < 0.01). When administered intraluminally, ethanol and xylose appeared in blood but only ethanol equilibrated fully between the lumen and blood. Intravenous infusions of ethanol and xylose, but not glucose, also delayed the return of phase III. When given intravenously, ethanol and xylose were recovered from the lumen, whereas glucose never was. Ethanol and xylose had comparable effects on the canine small bowel; they induced prolonged periods of irregular contractile activity and delayed the return of phase III. These effects were seen rapidly when solutes were administered intraluminally and more slowly when they were given intravenously. These results suggest that local luminal mechanisms stimulated by solutes influence small bowel motility, and they imply that the gut recognizes solutes whether or not these molecules are metabolizable.

Animals↗

PYY and GLP-1 contribute to feedback inhibition from the canine ileum and colon.

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).

Animal Nutritional Physiological Phenomena↗

Scintigraphy of the whole gut: clinical evaluation of transit disorders.

OBJECTIVE: To describe an initial clinical experience with a noninvasive scintigraphic technique for assessing gastrointestinal motility. DESIGN: We studied gastric, small bowel, and colonic transit in 109 unselected 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 ingestion 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.

Adolescent↗

Endoscopic esophageal manometry.

OBJECTIVE: We performed through-the-scope-manometry of the esophagus on 12 patients referred for esophageal symptoms. METHODS: A 3-lumen polyvinyl tube was passed through the biopsy channel of a standard video-endoscope. All patients underwent esophagogastroduodenoscopy with through-the-scope-manometry as well as a conventional laboratory-based manometric study; the sequence of the procedures was randomized. RESULTS: Mean lower esophageal sphincter pressure was 18 +/- 11 mm of mercury by both methods. In the lower esophagus, mean wave amplitude was 60 +/- 25 mm of mercury by through-the-scope manometry and 82 +/- 28 by laboratory testing. In the upper esophagus, mean wave amplitude was 50 +/- 26 mm of mercury by through-the-scope manometry and 63 +/- 20 by laboratory testing. Wave duration tended to be lower by through-the-scope manometry than by laboratory testing in the lower and upper esophagus. In nine patients with normal esophageal motility, 54% of swallows resulted in a peristaltic wave by the endoscopic study versus 100% for the laboratory test. CONCLUSION: Through-the-scope-manometry was able to accurately measure lower esophageal sphincter pressure compared with laboratory-based manometry. Peristaltic wave amplitude by through-the-scope manometry was reduced compared with laboratory-based manometry, most likely because of the use of dry swallows. Through-the-scope-manometry has promise as a screening test for esophageal motility disorders.

Endoscopy, Digestive System↗

Evaluation of an inexpensive screening scintigraphic test of gastric emptying.

UNLABELLED: Our goal was to study the accuracy of a limited assessment relative to the traditional and obtain a more detailed approach to measure gastric emptying. METHODS: We prospectively evaluated 35 patients referred to our laboratory with suspected fast or slow gastric emptying. Transit was measured radioscintigraphically after ingestion of an egg meal containing 99mTc-Amberlite pellets. Gastric emptying was analyzed by power exponential analysis. Diagnostic accuracy of simpler indices (gastric residual at 2 and 4 hr) was determined by comparing the categorization of patients as normal or abnormal relative to previously published normal data from our laboratory. RESULTS: Gastric residual at 2 hr showed greater diagnostic accuracy for accelerated gastric emptying with 90% sensitivity at 90% specificity. Gastric residual at 4 hr was less accurate for accelerated emptying, but was more accurate at detecting delayed gastric emptying with 100% sensitivity at 70% specificity. In contrast, sensitivity and specificity of gastric residual at 2 hr for slow emptying were low (100% sensitivity with 20% specificity) emphasizing the importance of obtaining a scan later than 2 hr for detecting delayed gastric emptying. CONCLUSION: Selective scans taken at 2 and 4 hr provide an excellent screening test for detecting fast or slow gastric emptying; the accuracy of 2-hr data is optimal for accelerated emptying and that of the 4-hr data greater for delayed emptying. This strategy provides a simple, less expensive way to evaluate gastric emptying in clinical practice with acceptable sensitivity and specificity as an initial test for patients with clinically suspected gastric stasis or dumping syndromes.

Anion Exchange Resins↗

Response of gastric fundus to rectal distension in healthy persons.

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.

Adult↗

Ileal distention relaxes the canine colon: a model of megacolon?

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 omega-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.

Animals↗

Pouchitis after ileal pouch-anal anastomosis: a Pouchitis Disease Activity Index.

OBJECTIVE: To develop a "Pouchitis Disease Activity Index" (PDAI) and to compare it with other diagnostic scoring systems for pouchitis. DESIGN: We compared patients who had an optimal outcome with those who had a poor result attributable to recurrent pouchitis after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis at the Mayo Clinic. MATERIAL AND METHODS: We evaluated the applicability of a PDAI that quantitated clinical findings and the endoscopic and histologic features of acute inflammation in four groups of patients: (1) 10 who underwent IPAA for ulcerative colitis and had symptoms compatible with a clinical diagnosis of pouchitis, (2) 5 who underwent IPAA for ulcerative colitis and did not have pouchitis, (3) 5 who underwent IPAA for familial adenomatous polyposis and had no symptoms of pouchitis, and (4) 5 who had a Brooke ileostomy for ulcerative colitis (control group). RESULTS: The PDAI was significantly greater in patients with the clinical features of pouchitis than it was for patients in the other three groups. All 10 patients with pouchitis fulfilled the PDAI criteria for a diagnosis of pouchitis; in contrast, only 1 of these 10 patients met the diagnostic criteria for pouchitis by application of previously established scoring systems. No asymptomatic patient qualified for a diagnosis of pouchitis by the PDAI criteria. CONCLUSION: The PDAI provides simple, objective, and quantitative criteria for pouch inflammation after IPAA and is more sensitive than prior scoring systems.

Adenomatous Polyposis Coli↗

A selective NK-2 antagonist blocks the increase of canine colonic tone and ileal contractions induced by the NK-2 selective receptor agonist, [beta Ala8] neurokinin A-(4-10).

BACKGROUND: The regulatory roles of tachykinins in intestinal motor function may be clarified by use of novel, stable and selective antagonists of neurokinin receptors. We studied the effects of the non-peptide NK-2 receptor antagonist SR48968 on canine colonic tone under resting conditions and after stimulation by the selective NK-2 receptor agonist [beta Ala8] neurokinin A-(4-10). METHODS: Experiments were performed in three conscious female dogs. Proximal colonic tone was recorded by a barostat and intraluminal pressures were recorded in the terminal ileum. 10, 15 and 20 cm orad to the ileocaecal junction. In separate experiments, and in a random sequence, dogs received an i.v. injection of the NK-2 antagonist SR48968, 10, 100, 1000 micrograms/kg, followed after 30 min by 2 micrograms/kg of the agonist [beta Ala8] neurokinin A-(4-10). Experiments were replicated twice in each dog. RESULTS: The NK-2 agonist increased colonic tone, and SR48968 antagonized these effects in a dose-dependent fashion (Spearman's rank, r = 0.86; P < 0.01); antagonism was complete at the highest dose. SR48968 alone had no effect on colonic tone and ileal motility. When given during phase I or II of the interdigestive motor complex, [beta Ala8] neurokinin A-(4-10) increased ileal contractions: pre-treatment with SR48968 blocked this increase in ileal motility. When given during phase III, [beta Ala8] neurokinin A-(4-10) interrupted the motility front; this effect was not antagonized by SR48968. CONCLUSIONS: SR48968 antagonizes the increase in canine colonic tone and ileal motility induced by activation of NK-2 receptors. However, SR48968 by itself had no effect on the control of colonic tone and ileal motility under unstimulated conditions. SR48968 may be useful for investigating the physiological role of tachykinins on the gastrointestinal tract.

Animals↗