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Biomedical subjects

S F Phillips

Publications and source records attributed to S F Phillips.

At least 145 records · Page 8Linked to original sources

The contribution of external ligamentous attachments to function of the ileocecal junction.

In 14 human autopsy specimens, obtained within two hours of death, the contribution of external ligamentous attachments to competence against reflux at the ileocecal junction (ICJ) was evaluated. The ascending colon was filled with saline by retrograde flow, and pressures at which coloileal reflux occurred were recorded. Twelve of 14 ICJ's were competent to pressures of up to 80 mm Hg; two incompetent ICJ's refluxed fluid into the ileum at intracecal pressures of approximately 40 mm Hg. Competent specimens were then restudied. Removal of mucosa at the ileocecal junction (N = 6), or a strip of circular muscle (N = 6), did not impair competence to pressures above 40 mm Hg. However, division of fibrous tissues which helped maintain an angulation between the ileum and cecum (superior and inferior ileocecal ligaments) rendered the junction incompetent in all specimens. In four samples tested, surgical reconstruction of the ileocecal angle restored competence. Comparable observations were made in three anesthetized dogs in vivo. These findings suggest that mechanical factors, maintained by the external anatomy, contribute to competence at the ICJ.

Animals↗

Emptying of the terminal ileum in intact humans. Influence of meal residue and ileal motility.

Emptying of the terminal ileum was assessed in 15 healthy humans by injecting technetium 99m-diethyltriaminopentaacetic acid into the bowel through a multilumen orocolonic tube. The subsequent arrival of isotope in the colon was quantified by gamma-scintigraphy and colonic filling curves were obtained. Studies were performed during fasting (n = 5) cnd 2.5 h after either a low residue meal (n = 5) or a meal made high in residue (n = 5) by adding 4 g of guar. The time for 50% of the isotope to reach the colon (T50) was significantly accelerated after both meals, being 72 +/- 15 min for the high residue meal and 62 +/- 8 min for the low residue meal, compared with 183 +/- 37 min (p less than 0.01) in the 5 fasting subjects. Although the addition of guar did not alter T50 significantly, it did cause a significant fall in the rate of colonic filling, implying increased isotope dilution. Delay at the ileocolonic junction, as shown by plateaus in the middle of the colonic filling curves, was uncommon. Hold-up was significant in only 2 of 10 postprandial and 2 of 5 fasting studies. Rates of ileocolonic transit could not be related to either a mean ileal motility index or the occurrence of specific ileal motor patterns immediately proximal to the ileocolonic junction. Fasting ileocolonic transit was characteristically erratic but could not be related to interdigestive migrating motor complexes, which were rarely observed in the last 60 cm of ileum. We conclude that ileocolonic transit in humans is related to the rate at which material accumulates in the ileum, being rapid postprandially (when ileal flow is high) and slow and erratic during fasting. This method yields consistent results and could be used to define further factors that influence ileocolonic inflow.

Adult↗

Altered small bowel motility in irritable bowel syndrome is correlated with symptoms.

The pathogenesis of irritable bowel syndrome (IBS) has been related more to dysmotility of the colon than to abnormalities of the small intestine. To look for small bowel abnormalities, we recorded ultraluminal pressures in 16 patients with IBS. All patients complained of abdominal pain, and diarrhea (n = 8) or constipation (n = 8) were also prominent symptoms. Comparable studies were performed on 16 age-matched controls. The observations include diurnal and nocturnal fasting recordings and the response to a fatty meal. Periodicities of the interdigestive migrating myoelectric complexes were shorter in IBS (p less than 0.05); this was due to much shorter diurnal cycles in patients with diarrhea (77 +/- 10 min) than those with constipation (118 +/- 15 min) or controls (113 +/- 10 min, both p less than 0.05). All groups exhibited circadian changes, with nocturnal cycles being more frequent. Two specific patterns of small bowel motor activity were more common in IBS--ileal propulsive waves and clusters of jejunal pressure activity (both p less than 0.05 compared to controls). Moreover, cramping abdominal pain was usually noted in IBS when ileal motility was propulsive; jejunal bursts were also sometimes associated with abdominal symptoms. We conclude that motility of the small intestine is modified in some patients with IBS and that certain motor patterns are related to their symptoms.

Abdomen↗

Simplified assessment of segmental colonic transit.

Transit times of radiopaque markers through the human gut were measured by published techniques and compared with a simplified method. Three sets of distinctive markers were ingested by 24 healthy persons on 3 successive days. In the first part of the study, daily abdominal x-rays were taken and individual stools were collected for radiography. Mouth-to-anus transits were assessed from the fecal output of markers and mean colonic and segmental colonic transits were calculated from the daily radiographs. These established methods were then compared with estimates of total colonic and segmental transits based on a single abdominal film, taken on the fourth day. The single-film technique correlated well with values obtained from the previous, but more inconvenient, methods. Using the simpler approach, colonic transit was assessed in 49 additional healthy subjects, for a total group of 73. Total colonic transit was 35.0 +/- 2.1 h (mean +/- SE); segmental transits was 11.3 +/- 1.1 h for the right colon, 11.4 +/- 1.4 h for the left colon, and 12.4 +/- 1.1 h for the rectosigmoid. Men had significantly shorter transits for the whole colon than did women (p less than 0.05), and this difference was apparent to some extent in the right (p = 0.06) and left colon (p = 0.07) but not in the rectosigmoid. Age did not influence transit significantly nor did a small dose of supplemental fiber. The technique is simple, convenient for clinical usage, and reduces the exposure to radiation to acceptable levels. There should be a role for this approach in the evaluation of colonic transit in selected patients.

Adult↗

Assessment of Campylobacter-like organisms in the postoperative stomach, iatrogenic gastritis, and chronic gastroduodenal diseases: preliminary observations.

Campylobacter-like organisms (provisionally named C. pyloridis) were demonstrated in gastric biopsy specimens by histopathologic analysis and bacterial culture. C. pyloridis organisms were found in 12 of 26 patients (46%) with gastric or duodenal ulcer but in none of 10 healthy volunteers without histologic evidence of gastritis. Iatrogenic antral gastritis, induced by 7 days of treatment with nonsteroidal anti-inflammatory drugs, was not associated with the presence of C. pyloridis. Organisms were found in 6 of 24 patients who had undergone gastric operations, but the prevalence of C. pyloridis was not higher in those with symptoms of alkaline reflux gastritis than in asymptomatic postgastrectomy control patients. We conclude that C. pyloridis is less common in patients with drug-induced and postoperative gastritis than in patients with peptic ulcer.

Campylobacter↗

Prognosis of chronic ulcerative colitis in a community.

Utilising the population based data resources of the Rochester Epidemiology Project, we estimated survival and risk of subsequent colon cancer in the 182 residents of Rochester, Minnesota, initially diagnosed with chronic ulcerative colitis (CUC) between 1985 and 1979. Twenty five (13.7%) had a proctocolectomy during the course of follow up. Three patients developed colorectal adenocarcinoma after the initial diagnosis of CUC (relative risk = 1.9, 95% CI 0.4-5.4). Excluding proctitis cases, the relative risk of cancer was 2.4 (95% CI 0.3-8.7). At last follow up, 37 (20.3%) were dead; only 10 patients had chronic ulcerative colitis mentioned on the death certificate. Overall survival was similar to that expected for the general population of like age and sex. Our results suggest that chronic ulcerative colitis in the community is typically a milder disease than would appear from hospital or referral centre series.

Adenocarcinoma↗

Chronic ulcerative colitis: incidence and prevalence in a community.

Utilising the population based data resources of the Rochester Epidemiology Project, we determined the incidence and prevalence of chronic ulcerative colitis among Rochester, Minnesota, residents over the 20 year period, 1960-79. One hundred and thirty eight cases met diagnostic and residency criteria, for an overall age, and sex adjusted chronic ulcerative colitis incidence rate of 15.0 per 100,000 person years. The male:female ratio of age adjusted rates was 1.5:1. Age specific incidence was roughly bimodal in appearance but was not consistent in different patient subgroups. On 1-1-80, there were 120 Rochester residents with a history of chronic ulcerative colitis, corresponding to a prevalence rate of 225.2 per 100,000 population. Fifty three per cent of chronic ulcerative colitis incidence cases were 'definite' and 47% were 'probable', the former requiring consistent observations for at least six months. The definite group had proportionately more men and disease of greater extent and severity. Pancolitis comprised about one-third of all cases (4.6 per 100,000 person years). Proctitis and distal disease (7.1 and 2.0 per 100,000 person years) made up most of the rest. One-fourth of all patients had 'severe' or 'moderate' disease (3.8 per 100,000 person years), while the remainder had either 'mild' or 'transient' chronic ulcerative colitis (11.2 per 100,000 person years). In residents of Rochester, Minnesota, chronic ulcerative colitis is most often a mild disease. The over-representation of severe or complicated examples that results from selected referral to major centres probably distorts the natural clinical spectrum of the disease.

Adolescent↗

Sensitivities of human jejunum, ileum, proximal colon, and gallbladder to cholecystokinin octapeptide.

We compared in humans simultaneous motor responses of the jejunum, ileum, proximal colon, and gallbladder (GB) to intravenous cholecystokinin octapeptide (CCK-OP). To gauge the physiological relevance of the doses of CCK-OP, intestinal motility and GB contraction were also quantified after a fatty meal. Eight healthy volunteers participated in both experiments. Six graded, 30-min intravenous infusions had a mean range of 2.2 to 73.2 pmol X kg-1 X h-1 of CCK-OP; these spanned from subphysiological (negligible contraction of GB) to pharmacological (producing intestinal symptoms and a 70-99% contraction of GB) levels. CCK-OP inhibited interdigestive cycles of motility, though in some persons fasting patterns persisted with doses of CCK-OP, which produced up to 50% reduction in GB volume. Motility indices of the ileum and proximal colon responded to CCK-OP by decreasing initially but then increasing with larger doses; motility of the jejunum increased gradually at all doses. Judged by the gallbladder's response to food (reduction in volume down from 74 to 29% of original volume), the physiological range of infused CCK-OP was approximately 5-16 pmol X kg-1 X h-1. Within this range of doses of CCK-OP, motility of the jejunum increased, whereas motility of the proximal colon was reduced. These data are consistent with CCK being a "physiological" mediator of intestinal motility in humans; responses of the intestine to the peptide appear to vary regionally.

Adult↗

Mechanisms of enhanced canine enteric absorption with intestinal pacing.

Electrical pacing enhances absorption from the canine small bowel, but the mechanism of this effect is unknown. To explore the mechanism, conscious dogs with two Vella loops, a proximal jejunal and a distal ileal, each 50 cm long, were studied. Pacing the jejunal loop with 15-18 pulses/min entrained the pacesetter potentials of the jejunal loop and increased water, sodium, and glucose absorption from the jejunal loop. Jejunal pacing also increased water absorption from the unpaced, ileal loop. Conversely, ileal pacing did not entrain the ileal loop or enhance absorption from the ileal loop. However, it did enhance water absorption in the unpaced jejunal loop. After alpha-blockade with phentolamine or celiac and superior mesenteric ganglionectomy, jejunal pacing did not increase jejunal or ileal absorption. In contrast, after beta-blockade with propranolol, pacing still enhanced jejunal absorption in three out of four dogs. Vagotomy alone enhanced jejunal but not ileal absorption, but the enhancement was not further increased by pacing. In conclusion, electrical pacing of the small bowel elicited a local and distant increase in net water absorption; the effect was mediated in part by an alpha-adrenergic mechanism.

Animals↗

Manometry of canine ileocolonic sphincter: comparison of sleeve method to point sensors.

Tonic and phasic pressures at the canine ileocolonic sphincter (ICS) were recorded by a manometric assembly that combined a sleeve sensor with multiple side-hole pressure ports. By aligning the side holes precisely it was possible to evaluate in vivo the fidelity of the sleeve relative to simultaneous pressure records from the point sensors. The ICS exhibited tonic and phasic pressures, often in excess of 100 cmH2O of pressure. The sleeve sensor was tolerant of small, but potentially important, movements of the assembly relative to the ICS. Point sites of recording moved in and out of the high-pressure zone and side holes were, therefore, not ideal sensors of sphincteric tone. The anticipated properties of this sleeve, that it would display reduced fidelity for rapid changes in pressure at sites away from its point of perfusion, were confirmed in vivo. The sleeve also "summarized" phasic bursts and was unable to monitor propagation of such events. However, the combined assembly proved excellent for examining overall function of the canine ICS.

Animals↗

Short-chain fatty acids stimulate motility of the canine ileum.

Based on earlier observations that colonic contents stimulated ileal motility in the dog, our hypothesis is that the ileum would respond to physiological amounts of short-chain fatty acids (SCFA). Four dogs had isolated ileocolonic loops constructed surgically and boluses of test solutions (15 ml) were instilled into the distal ileum through a small catheter. Intraluminal pressure catheters were used to record motility. Concentrations of SCFA (also called volatile fatty acids) comparable to those found in dog stool (108 mM; 66% acetic, 24% propionic, and 10% butyric acids) regularly stimulated motility with a dose-related effect. The response was not due to the pH of the SCFA solutions and was independent of the pH at which SCFA were instilled. Ricinoleic acid (4 mM) also stimulated motility, as did chenodeoxycholic acid; the bile acid was active only at supraphysiological concentrations (approximately 7.6 mM). Instillates that simulated the composition of ileal chyme in malabsorptive states were without effect. The results suggest that the ileum can "sense" the presence of colonic contents in the lumen and that SCFA are the responsible mechanisms. Stimulation of ileal motility by SCFA could be a response to coloileal reflux.

Animals↗

Altered sensitivity of the gallbladder to cholecystokinin octapeptide in irritable bowel syndrome.

We compared responses of the gallbladder to graded intravenous infusions of cholecystokinin octapeptide (CCK-OP) in normal controls (n = 8) and patients with irritable bowel syndrome (IBS) with predominant constipation (n = 8) or diarrhea (n = 8). The doses of CCK-OP ranged from subphysiological (negligible contraction of the gallbladder) to supraphysiological (90% contraction of gallbladder and abdominal side effects) amounts. All gallbladders contracted progressively in response to CCK-OP, and a Weibull model (power exponential function) described precisely the gallbladder's response to CCK-OP. Patients with IBS responded differently from normal patients; those with constipation contracted their gallbladders more and those with diarrhea contracted less in response to the peptide. Gallbladders were also stimulated with a high-fat, liquid meal; all patients' gallbladders contracted, but clear differences between groups could not be demonstrated postprandially. The results suggest that the smooth muscle of the gallbladder in IBS has an abnormal sensitivity to CCK-OP, and the results support the concept that IBS can be a generalized abnormality of the smooth muscle of the digestive tract.

Adult↗

Food restriction and recovery of nonabsorbed indicators from the small intestine of the rat.

Indicators of net water movement are used in a variety of intestinal transport studies. Such indicators should be virtually unabsorbed under study conditions. The effects of stimuli that alter intestinal mass on indicator recovery have not been examined. We used the male albino rat to study the effects of food restriction (50%) and fasting on recovery of indicators perfused intraluminally through the entire small intestine. Recovery of PEG 4000 and phenol red was essentially complete (98-100%) from control and restricted groups, but was 96% from the fasted group. PEG 400, consisting of a homologous series of polymers of which seven were measured (MW 242-506), was also perfused. The lower-molecular-weight polymers were absorbed. Absorption decreased with increasing molecular weight, and the slope of the relation of absorption to molecular weight was the same for all groups.

Animals↗

Decreased fluid tolerance, accelerated transit, and abnormal motility of the human colon induced by oleic acid.

To determine whether the presence of unabsorbed fat in the colon altered colonic motility, intraluminal pressures were recorded in the terminal ileum and proximal colon, and serial 1-min gamma camera scans were obtained while test solutions labeled with diethylenetetramine pentaacetic acid chelate of indium 111 were infused into the middle portion of the ascending colon. Seven subjects received a control solution, and 6 subjects received an emulsion of oleic acid (4.3 g/100 ml). Oleic acid accelerated colonic transit; isotope accumulated in the rectosigmoid faster in the first 120 min (4343 +/- 1175 cpm) than it did during control infusion (1236 +/- 348 cpm; p less than 0.01). Accelerated transit of oleate was accompanied by high amplitude (greater than 60 mmHg, range 60-95 mmHg), prolonged (greater than 10 s, range 10-48 s), propagated pressure waves; they originated near the ileocecal junction at a median frequency of 1.3 times/hour (mean 4.1, range 0.4-15.7). These were associated with a narrow image of the ascending colon on scintiscan and movement of 65.9% +/- 6.5% of counts from the ascending to transverse colon over the succeeding 4 min. A similar sequence was seen only once in 33 h of infusion with control solutions (p less than 0.01). Associated with these responses, the total volume of infusate tolerated before defecation was less with oleate than with control solutions (311 +/- 21 ml vs. 1049 +/- 71 ml; p less than 0.01). Long-chain fatty acids stimulated unusual motor patterns and reduced the reservoir function of the ascending colon; these effects may contribute to the diarrhea of patients with fat malabsorption.

Adult↗

Human interdigestive motility: variations in patterns from esophagus to colon.

In most fasting mammals, motility of the foregut and small intestine undergoes regular cycles of activity. Much of the expanding knowledge of this phenomenon comes from species other than humans; however, disorders of these patterns are proposed as being clinically important. We report studies in 16 healthy humans in whom motility was recorded from intraluminal pressure sensors, both when fasting and after a meal, for prolonged periods. The recording system spanned the area from stomach to proximal colon in all subjects and included the lower esophagus in 11 of the 16 studied. Half the interdigestive cycles involved the esophagus, approximately one-third began in the gastroduodenal region, and the remainder commenced more distally. Fewer than half the migrating motor complexes were recognizable beyond the midpoint of the small bowel, and less than 10% reached the distal ileum. The migrating motor complex was more prominent at night; and its progression through the jejunum was then slower. Small meals (345-395 kcal) interrupted fasting patterns for 90-240 min, but the amount of fat did not influence the duration of these disruptions. Motility varied widely between and within individuals, and differences between normal patterns in the jejunum and ileum were particularly striking. Thus, levels of recordings must be defined accurately if putative abnormalities, of possible clinical significance, are to be interpreted correctly. Relating local motor patterns to the maximal rate of rhythmic contractions, which reflects the frequency of slow waves and is a guide to the level of the small bowel, may be helpful in this regard.

Adult↗

Sulfapyridine appearance in plasma after salicylazosulfapyridine. Another simple measure of intestinal transit.

The appearance of sulfapyridine in plasma after oral administration of salicylazosulfapyridine (SASP) was evaluated as a method for defining arrival time in the cecum, an index of small bowel transit. After direct instillation of SASP and lactulose into the cecum, the appearances of their metabolites (sulfapyridine in plasma and hydrogen in breath) were rapid (1-10 min) and simultaneous. When a mixture of SASP and lactulose was taken by mouth, times of the respective "signals" varied among individuals from 40 to 180 min (n = 8) but were correlated within individuals. Salicylazosulfapyridine transit times from duodenum to cecum were also very similar to simultaneous measurements of transit by scintigraphic monitoring of technetium 99m. Timing of the sulfapyridine signal corresponded to the arrival of 5%-13% of technetium 99m DTPA in the cecum. Exemplifying the use of this new technique, simultaneous administration of lactulose into the stomach and SASP into the duodenum yielded consistently longer stomach-to-cecum than duodenum-to-cecum transits, attributable to the delay caused by gastric emptying. Therapeutic doses of morphine delayed small bowel transit of SASP. Transit of SASP offers a second marker technique for the cecal arrival of the "head" of a bolus; the approach may be useful as an inexpensive, noninvasive measurement of transit.

Adult↗

Scintigraphic measurements of canine ileocolonic transit. Direct and indirect effects of eating.

Eight dogs were equipped with ileal catheters, 50 cm proximal to the ileocolonic junction, and serosal electrodes at 5, 25, 55, 100, and 150 cm. Transit was assessed by injecting a bolus of 99mTc-diethylenetriamine pentaacetic acid through the ileal catheter and following isotope movements by serial, 4-min scintiscans. Isotope was injected in separate studies: during phase I of an interdigestive myoelectrical cycle, 10 min before a meal, and or 2 or 4 h after a meal (600 ml, 385 kcal, thickened with 4 g guar). At another time, mouth-to-colon transit of the same meal was measured by labeling it with 111In-diethylenetriamine pentaacetic acid and scanning at hourly intervals for 11 h. Transit of isotope through the terminal ileum and entry into the colon was characteristically erratic; long periods of immobility were interspersed with sudden "bolus" movements. In the fasting studies, most sudden movements occurred while phase III (migrating motor complex) of the interdigestive myoelectrical cycle migrated through the last 50 cm of ileum. Passage of a single migrating motor complex through the terminal ileum propelled about one-half the dose of isotope into the colon; complete clearance of the ileum required two or more migrating motor complexes. Immediately after the meal, ileal movements increased transiently; however, these were followed by a period of quiescence. Overall, the time for 50% of the counts to enter the colon was not different when isotope was injected 10 min before the meal from when the injection was made 2 h postprandially (207 +/- 16 min and 162 +/- 25 min, respectively). However, transit of isotope injected 4 h postprandially was significantly faster (91 +/- 13 min). In the fed state, some bolus movements could be related to specific patterns of ileal motility; however, the majority occurred during apparently random "fed-type" motility. In part II, meal marker accumulated faster in the colon after 3-4 h, suggesting that the rapid ileocecal transit at 4 h postcibal was due to increased flow of chyme through the ileum at this time.

Animals↗