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Biomedical subjects

S F Phillips

Publications and source records attributed to S F Phillips.

At least 181 records · Page 10Linked to original sources

Myoelectric activity and intraluminal pressure of the canine ileocolonic sphincter.

We constructed ileocolonic loops of distal ileum, ileocolonic sphincter, and proximal colon in 5 dogs; neuromuscular continuity was maintained between loop and intact bowel by a bridge of tunica muscularis. To study ileocolonic sphincter function, we recorded myoelectric activity from subserosal electrodes and intraluminal pressures from perfused catheters and a sleeve sensor. Recordings included at least one interdigestive myoelectric complex and four postprandial hours. Ileal slow waves were recorded from the loop and the ileocolonic sphincter; most interdigestive myoelectric complexes were propagated to the ileocolonic sphincter. Intraluminal pressures at the ileocolonic sphincter fluctuated phasically (mean 12.5 cycles/min) for 72% of recording time during fasting and 81% postprandially. Tonic pressures at the ileocolonic sphincter were higher during fasting (31 +/- 18 cmH2O; p less than 0.05) than postprandially (24 +/- 20 cmH2O); moreover, tonic pressures fluctuated more during fasting than after food. Tonic elevations of pressure were prolonged (mean duration 28.5 min) concomitant with arrival of phase 3 of interdigestive myoelectric complexes at the ileocolonic sphincter. Thus the ileocolonic sphincter participates in both the myoelectric and motor components of the interdigestive cycle and exhibits an intense phasic and tonic response to phase 3. The association of tonic pressure and intense phasic contractions may serve to retard and segment ileal chyme. On the other hand, the presence of rapidly propagated phasic pressures in the region may provide the basis for propulsive function. In this way, these unique motor events will facilitate two distinct functions of the region, namely the alternate retarding and forward propulsion of chyme.

Animals↗

The ileocecal (ileocolonic) sphincter.

The ileocolonic junctional region exhibits many features considered characteristic of a gastrointestinal sphincter. Thus the junction between large and small bowel is marked in many species by considerable thickening of the circular muscle coat, and physiological studies have revealed properties similar to other sphincteric areas. The region generates a tonic pressure and exhibits responses to distension, nerve stimulation and pharmacological agents clearly different from adjacent ileum and colon. The factors responsible for generating and maintaining tone within this sphincter remain unclear, however. While extrinsic nerves do not appear to play a significant role, importance has been variously attributed to the contributions of intrinsic nerves, myogenic tone and elastic factors. The function of this region in the intact animal has not been extensively investigated or clearly defined. However observations in both animals and man suggest that the ileocolonic sphincter acts in concert with adjacent ileum to store chyme in the distal small bowel and periodically expel it into the colon. Coordinated activity is especially noticeable following food when increased ileal activity combined with relaxation of the sphincter promotes rapid emptying of ileal contents. Clinical and experimental studies indicate that the presence of an intact ileocolonic sphincter may increase survival and reduce morbidity following extensive small bowel resection. By preventing reflux of colonic contents the sphincter may serve to minimize colonization of the small bowel by large bowel bacterial flora. The response of the ileocolonic sphincter to large bowel distension appears highly variable and may depend more on the magnitude of the intracolonic pressure generated rather than on inherited or acquired abnormalities of junctional zone anatomy.

Animals↗

Passage of carbohydrate into the colon. Direct measurements in humans.

To quantify passage of unabsorbed dietary starch into the colon, 7 healthy volunteers had a multilumen tube positioned close to the ileocecal junction. Marker solution was perfused slowly, 20-40 cm above an aspiration site, to estimate, by marker dilution, flow through the ileum. On consecutive days, subjects ate liquidized meals containing 20 or 60 g starch; ileal aspirates were analyzed for starch and glucose for 5-6 h fasting and 4-7 h postprandially. Volume and carbohydrate concentrations were used to derive total carbohydrate traversing the ileum. In different subjects, unabsorbed carbohydrate was 453-4023 mg (2.3%-20.1%, mean 9.3%) for the smaller meal and 1332-6352 mg (2.2%-10.4%, mean 6.0%) for the larger. In 4 volunteers, hydrogen breath tests were performed on separate occasions after sucrose (50 g), lactulose (26 g), and the 20-g meal. Lactulose increased hydrogen excretion; sucrose and the test meal did not. We conclude that 2%-20% of dietary starch escapes absorption in the small bowel, confirming others' results using breath tests alone. Breath tests, though more convenient than intubation studies, may be a less sensitive index of starch malabsorption.

Adult↗

Components of fiber bind iron in vitro.

Interactions among fiber, inorganic iron, and substances known to chelate iron were examined in vitro. Cellulose, neutral and acid fractions of lignin, psyllium mucilage, and pectin were incubated with 59Fe SO4 at various pH's, in various concentrations, and in the presence or absence of known chelators of iron including ascorbate, citrate, cysteine, fructose, and EDTA. Insoluble components of fiber were tested in a precipitation-centrifugation system, soluble components were tested by equilibrium dialysis. Lignins and psyllium mucilage had the greatest capacity to bind ferrous iron under conditions that approximated those of the proximal intestine postprandially; cellulose and pectin were less potent. Dissociation constants of binding were similar for several components, suggesting the existence of comparable binding sites in different components of fiber. Citrate and EDTA inhibited the binding of iron markedly but other chelators were much less effective. These reactions among fiber, inorganic iron, and other constituents of food may influence the bioavailability of dietary iron and the simple systems described here offer a means of dissecting interactions that are complex in vivo.

Cellulose↗

Components of fiber impair iron absorption in the dog.

We have demonstrated previously that semipurified components of fiber bind ferrous iron in vitro. The present studies examined the possibility that these same fibers would decrease absorption of iron by the canine small bowel. Healthy and anemic dogs were studied chronically. Two preparations were needed; soluble components of fiber were tested by continuous perfusion of a duodenojejunal segment of approximately 100 cm, insoluble components were tested in Thiry-Vella fistulae of jejunum (25 cm). The results confirm that, 1) anemic dogs absorb iron more efficiently than do healthy animals, and 2) that there is a slight, but significant, decrease in iron absorption during the 4 to 6 h of an acute experiment. To obviate problems of interpretation because of the latter point, all studies featured a control period, before and after, the test period. Lignin and psyllium mucilage were potent inhibitors of iron absorption, pectin less so, and cellulose was without effect in this system. The results in vivo correlate well with the binding of iron in vitro.

Anemia, Hypochromic↗

Physiologic aspects of continence after colectomy, mucosal proctectomy, and endorectal ileo-anal anastomosis.

We examined the physiology of continence in 12 patients at least four months after colectomy, mucosal proctectomy, and endorectal ileo-anal anastomosis for ulcerative colitis and familial polyposis. The mean fecal output (+/-SEM) was 598 +/- 60 gm, passed as 12 +/- 4 movements/24 hr, of which 4 +/- 1 were passed at night. The patients were generally continent during the day and could distinguish gas from stool, but 11 of 12 leaked stools at night. Anal sphincter resting pressures (71 +/- 8 cm H2O) and squeeze pressures (171 +/- 15 cm H2O) of patients were similar to those of ten healthy controls (P greater than 0.05), although the rectal inhibitory reflex was absent in the patients. After operation, the distal bowel had a pressure-volume curve of greater slope (0.15 +/- 0.05 ml/cm H2O) than it had in controls (0.07 +/- 0.01 ml/cm H2O, P less than 0.05) and a lesser maximum capacity (patients, 248 +/- 31 ml; controls, 406 +/- 26 ml; P less than 0.05). The greater the capacity of the neorectum, the fewer was the number of bowel movements/day (r = 0.91, P less than 0.001). We concluded that the operation preserved the anal sphincter, although it decreased the capacity and compliance of the distal bowel and impaired continence.

Adult↗

Parallel gastric emptying of nonhydrolyzable fat and water after a solid-liquid meal in humans.

Our aim was to examine the control of gastric emptying of the oil phase of a mixed solid and liquid meal. Previous studies had shown that liquid dietary fats normally leave the stomach at a slower rate than does water. We wished to determine whether the slower emptying of fats was due to the physical characteristics of food (lower density and greater viscosity than water), to retardation by duodenal feedback mechanisms, or whether both factors contributed. Thus, we quantified the emptying rates of water and sucrose polyester (a nonabsorbable analog of dietary fat) ingested by healthy volunteers as a mixed solid and liquid meal. Gastric emptying was quantified by an intubation-perfusion method incorporating an occlusive jejunal balloon to facilitate recovery. Four phase-specific, nonabsorbable markers were used. [14C[Sucrose octaoleate and polyethylene glycol were incorporated in the meal and traced the lipid and water phases, respectively; [3H]glycerol triether and phenolsulfonphthalein were used as duodenal recovery markers. Sucrose polyester (substituting for dietary fat) was emptied very rapidly, and at about the same rate as was water, in contrast to natural fat, which empties very slowly. Emptying of water was rapid and comparable to that observed after mixed meals containing natural fat. These results imply that gastric emptying of the oil phase is controlled by receptors sensitive to the hydrolytic products of fat digestion and that the slow emptying of dietary fat is not simply due to its lower density.

Adult↗

Human platelet phenol sulphotransferase: assay procedure, substrate and tissue correlations.

Procedures for the precise assay of human platelet phenol sulphotransferase activity were determined. The coefficient of variation of the assay was 5.8% when the enzyme activity was expressed per 10(8) platelets, and was 9.4% when it was expressed per mg soluble platelet protein. Mean platelet phenol sulphotransferase (PST) activity in samples from 102 randomly selected adults was 1.2 +/- 0.4 units/10(8) platelets (mean +/- S.D.), with a range from 0.2 to 2.9. The mean activity for umbilical cord blood platelet PST was 0.93 +/- 0.3 units/10(8) platelets (mean +/- S.D., n = 27). The substrate used routinely for the assay was 3-methoxy-4-hydroxyphenylglycol (MHPG). There was a significant correlation between the formation of MHPG sulfate by individual platelet preparations and the formation of sulfated product with each of the following substrates: tyramine (r = 0.92, n = 21); dopamine (r = 0.82, n = 16); 5-hydroxytryptamine (r = 0.94, n = 20); acetaminophen (r = 0.77, n = 17); and alphamethyldopa (r = 0.77, n = 17) (p less than 0.001 for each). Platelet PST activity correlated significantly with human renal cortex PST activity (r = 0.54, n = 20, p less than 0.02). The correlation coefficient between platelet PST activity and jejunal mucosal enzyme activity in eight patients was 0.67. These results raise the possibility that human platelet PST activity measured with MHPG as substrate might reflect the enzyme activity in other tissues and the degree of sulfate conjugation of a variety of substrates.

Adult↗

Feeding augments canine jejunal absorption via a hormonal mechanism.

The aim of this study was to determine whether hormones mediate the postprandial increase in absorption of water, glucose, and electrolytes that occurs in the canine jejunum. In four dogs, a 75-cm isolated loop of jejunum was extrinsically denervated by autotransplantation. After recovery, the loop was perfused at 2.8 ml/min with an isotonic solution of 130 mM glucose, 80 mM NaCl, and trace amounts of [14C]PEG. Mean transit times through the loop were assessed concurrently with 0.5-ml boluses of [3H]PEG. Experiments were performed during fasting and after an oral meal of 200 g liver. Under steady-state conditions, net absorption of water, glucose, sodium, and chloride was greater after feeding than during fasting. In contrast, mean transit times were nearly identical during fasting and after feeding. We concluded that the augmentation of jejunal absorption of water, glucose, and the electrolytes after feeding was brought about by mechanisms other than alterations in transit time or effects induced via the extrinsic nerves. The augmentation appeared to be mediated, in part, by hormones.

Action Potentials↗

Ricinoleic acid causes secretion in autotransplanted (extrinsically denervated) canine jejunum.

To examine the role of extrinsic nerves and hormones in intestinal secretion of fluid, we studied the effect of ricinoleic acid on absorption by isolated, autotransplanted jejunal loops in four dogs. Compared to perfusion with control solution, the addition of ricinoleic acid caused reversible secretion of water and electrolytes and inhibition of glucose absorption, as previously described in the innervated intestine. In contrast, oral castor oil caused diarrhea but had no effect on absorption from the denervated loop. Thus, the secretory action of ricinoleic acid is maintained without the influence of extrinsic nerves; in addition, further support is added to the proposal that hormones do not mediate secretion in this model. These findings support a local mechanism for the secretion induced by ricinoleic acid.

Animals↗

Gastric emptying of lipids after ingestion of a solid-liquid meal in humans.

We measured gastric emptying of fat and water from a mixed meal in 6 healthy volunteers using a technique of duodenal perfusion that included phase-specific, nonabsorbable markers. Pairs of water-soluble markers (polyethylene glycol 4000 and phenolsulfonphthalein) and (equivalent) lipid-soluble ([14C]sucrose octaoleate and [3H]glycerol triether) markers were used. For each pair, one marker was used to label the corresponding component of the meal (water of fat), and the other was perfused into the duodenum as a recovery marker. The perfusion method was validated by comparing the amount of marker emptied, as estimated by marker dilution, with the amount obtained by complete aspiration of intestinal contents proximal to an occlusive balloon. Throughout the postprandial period, ratios of lipid marker to total fatty acids in the stomach remained constant, indicating a stable relationship of meal marker to total lipids. Water always emptied faster than did lipids, substantial amounts of which were still in the stomach after 6 h. There was close agreement between recovery of fat proximal to the balloon and calculations of lipid emptying from duodenal perfusion, supporting the validity of the marker dilution technique for the gastric emptying of lipids. This study demonstrates that when ingested as part of an ordinary mixed meal, water and fat have different patterns of emptying, water leaving the stomach first.

Adult↗

Achieving ileostomy continence with an indwelling stomal device.

To determine whether intermittent occlusion of a Brooke ileostomy could be tolerated and achieve continence without impairing intestinal function, we constructed such ileostomies in seven dogs. After initial assessment of ileal diameter, compliance, transit, and absorption, four dogs underwent progressively lengthening periods of ileostomy occlusion, with the use of an indwelling intraluminal device. Three dogs served as unobstructed control subjects. All dogs were restudied after 20 weeks. Both occluded and control animals remained healthy, regaining and maintaining their preoperative weights. Complete continence for gas and stool was achieved without distress during periods of occlusion up to 6 hours twice a day. After the device was removed, the ileum emptied promptly. Occluded dogs developed amore dilated, compliant distal ileum with slower transit than did the control dogs. However, ileal absorption of water, glucose, sodium, and chloride, ileal secretion of potassium, and enteric absorption of fat were not impaired by occlusion; these indices did not change during 20 weeks in occluded or control animals. We concluded that chronic intermittent ileostomy occlusion in dogs was well tolerated, achieved fecal continence, slowed ileal transit, and resulted in the formation of a functional ileal reservoir without impairing enteric absorption.

Animals↗

Recovery of dietary iron and zinc from the proximal intestine of healthy man: studies of different meals and supplements.

The technique of marker perfusion of the upper gastrointestinal tract was used to measure intraluminal quantities of iron and zinc after test meals in healthy humans. Two different meals, one based on hamburger (with a predominance of heme iron, 7.5 mg/meal) and one based on cereal (containing inorganic iron; 1.4, 5.3, or 4.6 mg), were used. In addition, the luminal behavior of ferrous sulfate and hydrogen-reduced metallic iron (used as supplements to the cereal meal) were compared. Different meals also contained low (2.4 mg) or high (5.5 mg) amounts of zinc. The intubation techique allowed disappearance of metals from the duodenum and jejunum to be compared. The patterns of luminal flow were different for iron and zinc. Whereas iron was never recovered from the lumen at levels above those ingested in meals, zinc was recovered from the duodenum at levels greater than those ingested. These findings suggest that zinc, but little iron, is added to chyme in the upper gut during digesting and absorption. Bioavailability of different forms of iron, as judged by their luminal disappearance, were similar. Inorganic iron, ferrous sulfate, and hydrogen-reduced metallic iron were absorbed about as effectively as was heme iron. Iron disappeared preferentially from the duodenum but the site of zinc absorption appeared to be more distal.

Adult↗