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Biomedical subjects

S F Phillips

Publications and source records attributed to S F Phillips.

At least 91 records · Page 5Linked to original sources

Colonic tone and motility in patients with irritable bowel syndrome.

In this study, our aim was to test the hypothesis that colonic tone is abnormal in patients with irritable bowel syndrome (IBS). We studied eight patients with IBS and eight age-matched asymptomatic control subjects, in whom tone and motility were measured by an electronic barostat and by pneumohydraulic perfusion manometry, respectively. Tone and motility were recorded from the descending colon for a 14-hour period--3 hours awake, 7 hours asleep, 2 hours fasting after awakening, and 2 hours postprandially. In patients with IBS and in healthy subjects, colonic tone decreased by up to 50% during sleep and increased promptly on awakening. Fasting colonic tone (as quantified by the volume in the barostat balloon) in the awake state was not significantly higher in patients with IBS than it was in healthy subjects (125 +/- 13 versus 152 +/- 15 ml; P = 0.19). Tone increased postprandially in both study groups, and the increase was greater in healthy subjects than it was in patients with IBS (P < 0.05). The motility index during fasting was greater in patients with IBS than it was in healthy control subjects (3.2 +/- 0.6 versus 1.6 +/- 0.4; P = 0.05), and the postprandial increase in motility index was greater in the healthy subjects. Preprandially and postprandially, we noted a trend for high-amplitude prolonged contractions to be more frequent in patients with IBS than in healthy subjects. We conclude that colonic tone in patients with IBS showed the same nocturnal and postprandial variations as it did in healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Selective 5-hydroxytryptamine type 3 receptor antagonism with ondansetron as treatment for diarrhea-predominant irritable bowel syndrome: a pilot study.

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Control of muscle tone in the human colon.

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.

Adult↗

Response of canine ileocolonic sphincter to intraluminal acetic acid and colonic distension.

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.

Acetates↗

Zollinger-Ellison syndrome. Relation to Helicobacter pylori-associated chronic gastritis and gastric acid secretion.

Since Helicobacter pylori infects the gastric mucosa in most patients with chronic duodenal ulcer, infection with this organism has been implicated in the pathogenesis of this common disease. We postulated that if H. pylori is pathogenic in the usual type of duodenal ulcer, it should be less common when duodenal ulcer has another, specific etiology, such as Zollinger-Ellison syndrome. Gastric mucosa was compared from 18 patients with proven Zollinger-Ellison syndrome (17 of whom had had duodenal ulcer disease) and 18 controls with chronic duodenal ulcer without such a diagnosis. All subjects, who were matched for age and sex, had undergone elective gastric resections. Gastric tissues were stained by hematoxylin-eosin and Giemsa and were reviewed by an experienced pathologist who was unaware of the diagnosis. The frequency of H. pylori in patients with Zollinger-Ellison syndrome (8/18) was lower than in controls with duodenal ulcer (16/18; P less than 0.02). Moreover, chronic antral gastritis scores were higher in patients with duodenal ulcer (P less than 0.01). In Zollinger-Ellison syndrome, peak acid output was lower in patients positive (median 22 meq/30 min) compared to those negative for H. pylori (median 32 meq/30 min; P less than 0.02) but serum gastrin was correspondingly lower in patients positive for H. pylori (P less than 0.05). H. pylori infection appears to be more frequent when duodenal ulceration is not associated with another etiology, such as acid hypersecretion in Zollinger-Ellison syndrome. H. pylori infection in Zollinger-Ellison syndrome may also be associated with decreased gastric acid secretion.

Adolescent↗

Prevalence of Helicobacter pylori in specific forms of gastritis. Further evidence supporting a pathogenic role for H. pylori in chronic nonspecific gastritis.

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.

Adolescent↗

Variation of muscle tone in the human colon.

It was hypothesized that the human colon is able to relax or constrict to receive materials arriving from above or to hasten distal passage of contents. Dilatation is also a feature of several pathophysiological states and, therefore, the propensity of the colon to dilate might be important in disease. An electromechanical barostat was applied to the human colon, and changes in colonic tone were recorded in response to physiological perturbations. In 16 studies of 14 healthy volunteers, the colon was prepared for colonoscopy and a manometry-barostat assembly was positioned in the ascending (n = 5), transverse (n = 4), or descending (n = 7) colon. The influences of food and overnight sleep were recorded. The barostat continuously monitored, at a constant pressure, the volume of air within a highly compliant 10-cm bag. Changes in tone, as reflected by changes in bag volume, were usually unassociated with waves of intraluminal pressure recorded from adjacent manometric sites. Thus, the barostat revealed a motor phenomenon not readily apparent by conventional manometry. Food caused an immediate though slowly progressive increase in tone; however, bag volumes were greatest during overnight sleep and were decreased on waking. The barostat has the potential to explore another possibly important aspect of colonic function in humans.

Adolescent↗

Human anal motility while fasting, after feeding, and during sleep.

The aim of this study was to determine whether the human anal sphincter responds dynamically to changing physiological states. In 19 healthy human subjects, intraluminal anal canal pressure was measured with a 5-cm perfused sleeve sensor during the day while fasting (3 hours) and after feeding (3 hours) and at night during sleep (8 hours). Daytime mean anal canal pressures (+/- SEM) while fasting (50 +/- 3 mm Hg) were similar to those after feeding (49 +/- 3 mm Hg) and to those at night during sleep (49 +/- 3 mm Hg). Marked minute-to-minute variations in mean pressure occurred in all three periods, however, as did large phasic increases and decreases in pressure (greater than 20 mm Hg) and small phasic changes in pressure less than 20 mm Hg (anal slow waves). The minute-to-minute variations in mean pressure were greater during the awake fed state (4 +/- 1 mm Hg/min) than at night during sleep (2 +/- 1 mm Hg/min; P less than 0.03), as were the number of large phasic waves per minute (increases in pressure: awake, fed = 0.5 +/- 1 waves/min, night = 0.3 +/- 0.1 waves/min, P less than 0.05; decreases in pressure: awake, fed = 0.4 +/- 0.1 waves/min, night = 0.2 +/- 0.1 waves/min, P less than 0.05). Anal small waves had a similar frequency of about 17 waves/min in all three states. In conclusion, the anal sphincter maintains a continuous pressure barrier to rectal outflow both during the day and at night during sleep. However, marked minute-to-minute variations in mean pressure and large phasic increases and decreases in pressure do occur. Both are fewer at night during sleep.

Adult↗

Unprepared human colon does not discriminate between solids and liquids.

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.

Adult↗

Canine ileocolonic sphincter: flow, transit, and motility before and after sphincterotomy.

Our hypothesis was that the canine ileocolonic sphincter (ICS), per se, would have little regulatory effect on the transit of chyme from ileum to colon. We argued, from earlier observations, that the ileocolonic junction was influenced more by functional motor integration of the ileum, ICS, and proximal colon. In five dogs, the ileocolonic sphincter was ablated by extramucosal sphincterotomy; the operation significantly lowered tonic pressures at the ICS. Animals were then studied in the fasting state and postprandially. Ileal flow was estimated by marker dilution, and ileocolonic flow was estimated by total recovery of chyme from a colonic cannula. Transit times were measured after the bolus infusion of nonabsorbable markers. Ileocolonic sphincterotomy did not significantly alter flow rates or transit times of chyme across the ICS, although ileal motor patterns were changed after sphincterotomy. We concluded that the ICS probably has only a small effect on transit and flow at the ileocolonic junction. These findings argue for the importance of integrated motility of the ileum, ICS, and proximal colon in controlling the flow of chyme in this region.

Animals↗

Measurement of tone in canine colon.

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.

Animals↗

Abnormal gallbladder motility in irritable bowel syndrome: evidence for target-organ defect.

We have described previously that the gallbladder responds abnormally to infusions of cholecystokinin octapeptide (CCK-8) in patients with irritable bowel syndrome (IBS). To confirm these results and to examine the possible mechanisms, patients with IBS and predominant symptoms of diarrhea or constipation were compared with matched controls. During infusions of CCK-8 at one of three doses, the response of the gallbladder was measured ultrasonographically. The levels of CCK-8 reached in the peripheral circulation and degradation of the peptide in vitro and in vivo were used to evaluate metabolism of cholecystokinin. We confirmed that the gallbladders of patients with IBS responded abnormally to CCK-8; however, the differences were not due to any prereceptor event. Instead, this abnormality in IBS must be explained by an atypical response at the level of the target tissues.

Adult↗

The ileocecal area and the irritable bowel syndrome.

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.

Animals↗

[14C]urea breath test for diagnosis of Helicobacter pylori.

H. pylori is a potent urease producer, a characteristic that has been exploited in the development of the [14C]- and [13C]urea breath tests. The prevalence of H. pylori infection also is known to increase with advancing age; however, the individual patient's age has not routinely been considered when interpreting urea breath test results. The aim of this study was to validate a short, age-adjusted [14C]urea breath test for use in diagnosing H. pylori infections. Forty-one subjects (28 volunteers, 13 patients) underwent esophagogastroduodenoscopy with biopsies. Subjects were defined as being H. pylori-positive if histology or culture was positive. In addition, all subjects completed a 120-min [14C]urea breath test. A logistic regression analysis adjusting for age was used to estimate the probability of H. pylori positivity as a function of the 14C values generated. Sixteen subjects were H. pylori-positive, and 25 were H. pylori-negative. The 14C values generated between 15 and 80 min were found to be equally predictive in identifying H. pylori-positive subjects. Advancing age was associated with a higher probability of H. pylori-positivity. By taking advantage of the statistical probabilities, older patients could be accurately diagnosed with H. pylori at lower 14C values. We found that [14C]urea breath test to be both a sensitive and specific test that can be abbreviated to a 30-min examination (total test time). Moreover, our mathematical model indicates that a patient's age should be considered in order to optimize interpretation of the [14C]urea breath test, although further observations are needed to confirm this model.

Age Factors↗

GR 38032F (ondansetron), a selective 5HT3 receptor antagonist, slows colonic transit in healthy man.

The newly recognized class of 5-hydroxytryptamine receptors (5HT3) may be involved in the induction of nausea, since their pharmacological antagonists are effective against emesis induced by chemotherapy. 5HT3 receptors are present on enteric neurons, and 5HT3 blockers may produce mild constipation; we thus hypothesized that 5HT3 receptors would modulate colonic motility. To determine if GR 38032F, a selective 5HT3 antagonist known to have antiemetic effects, influences colonic transit in health, a randomized, double-blind, placebo-controlled crossover study was performed. Using a radiopaque marker technique, colonic transit was quantified in 39 healthy volunteers (19 men, 20 nonpregnant women) 18-70 years of age. On a standard 25-g fiber diet, 16 mg of GR 38032F was given orally thrice daily. Gastrointestinal peptides (peptide YY, human pancreatic polypeptide, neurotensin, motilin, gastrin-cholecystokinin, substance P) were also measured in plasma fasting and postprandially. Mean total colonic transit time on placebo was 27.8 hr, while on GR 38032F it was 39.1 hr (P less than 0.0005). Transit times through the left colon (P less than 0.0005) and rectosigmoid (P less than 0.05) were prolonged by the drug, but right colonic transit was not significantly altered. Transit times did not correlate with age or gender, but subjects with shorter transit times were significantly more affected than were those with longer transit times. The peak release of peptide YY was minimally decreased following GR 38032F (P less than 0.01), but the peak and integrated postprandial responses of human pancreatic polypeptide, neurotensin, motilin, gastrin-cholecystokinin, and substance P were not significantly altered by the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗