Biomedical subjects
S F Phillips
Publications and source records attributed to S F Phillips.
Effects of long chain fatty acids on solute absorption: perfusion studies in the human jejunum.
Perfusion studies were performed in healthy volunteers to test the hypothesis that net fluid secretion induced by fatty acids is accompanied by parallel reduction in solute transport. Ricinoleic acid provoked a marked net secretion of fluid and concomitantly inhibited the absorption of all solutes tested; these included glucose, xylose, L-leucine, L-lysine, Folic acid, and 2-mono-olein. Oleic acid also reduced net fluid and solute transport, but was less potent in reducing solute absorption than was ricinoleic acid. When fluid secretion was induced osmotically with mannitol, glucose and xylose absorption was not affected. The mechanism for this generalised effect of fatty acids on solute absorption is uncertain, possibly nonspecific, and might be related to mucosal damage and altered mucosal permeability induced by these agents.
Device for obtaining multiple simultaneous samples of intestinal contents during perfusion studies in man.
A system is described for obtaining frequent simultaneous samples from three jejunal sites. It can be easily made from materials ordinarily available in any laboratory.
Cytotoxicity of ricinoleic acid (castor oil) and other intestinal secretagogues on isolated intestinal epithelial cells.
Epithelial cells were isolated from hamster small intestine by a technique of vibration and used to measure cytotoxicity in vitro of certain substances known to stimulate intestinal fluid secretion. These secretagogues have laxative properties and produce mucosal damage in vivo. Compounds tested were ricinoleic acid (caster oil), dioctyl sodium sulfosuccinate, oleic acid, sodium deoxycholate and sodium cholate. Cytotoxicity was assessed by: 1) exclusion of trypan blue; 2) release of intracellular (prelabeled) 51Cr; and 3) inhibition of cellular uptake of 3-O-methylglucose. Ricinoleate produced a dose-dependent (0.1-2.0 mM) cytotoxicity as assessed by all three methods. Oleic acid, a nonhydroxylated analog of ricinoleate, was less potent. The dihydroxy bile acid, deoxycholate, was equipotent with ricinoleate, was less potent. The dihydroxy bile acid, deoxycholate, was equipotent with ricinoleate but its trihydroxy congener, cholate, was less potent. Dioctyl sodium sulfosuccinate had cytotoxicity similar in magnitude to that of ricinoleate and deoxycholate. Cytotoxicity of these agents to isolated cells may relate to their secretory potential in vivo, their abilities to produce structural change at the mucosal surface and their laxative properties.
Electrical pacing increases jejunal absorption of water, glucose, and sodium.
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Perfusion of rabbit colon with ricinoleic acid: dose-related mucosal injury, fluid secretion, and increased permeability.
Morphology of the rabbit colon was examined by light and scanning electron microscopy after perfusion of the organ with 2.5, 5.0, 7.5, and 10 mM sodium ricinoleate. Colons perfused with control buffer showed the expected normal appearances, whereas ricinoleate produced desquamation of surface epithelial cells. Surface changes in the colon were comparable with those reported after similar treatment of the rabbit ileum. Concomitant with these histological changes was loss of DNA into the lumen of the colon. Dose-related changes in net fluid transport and mucosal permeability (as assessed by lumen to plasma flux of low molecular weight polyethylene glycols and plasma to lumen flux of urea and creatinine) were also associated with ricinoleate perfusion. These structural and functional alterations may contribute to intraluminal accumulation of fluid and catharsis that can result from administration of ricinoleic acid (castor oil). The findings might also pertain to the pathophysiology of steatorrheal diseases, because dietary fatty acids of similar chemical structure are known to have comparable effects on the intestinal mucosa.
The continent ileal pouch: absorptive and motor features.
In 8 patients, 6 to 40 months after proctocolectomy and construction of a continent ileal pouch, selected absorptive and motor functions of the pouch were assessed. Test solutions of 100 or 200 ml, containing a nonabsorbable marker, were placed in the pouch and sampled serially for 1 hr; an oro-intestinal tube was used to prevent contamination of the pouch by endogenous secretions. Sodium, chloride, and water were absorbed in a fashion similar to that reported previously for normal ileum. Similarly, the resting mucosal potential difference and its response to glucose were like those of normal ileum. The pouch also absorbed vitamin B12 that was instilled together with intrinsic factor. The distribution of primary and secondary bile acids in duodenal content suggested that decreased dehydroxylation of bile acids, also seen after conventional ileostomines, occurs in pouch patients. The pattern of motility in pouches was consistent with that reported previously for normal ileum. Thus, the functions of the mucosa and smooth muscle of the continent ileal pouch are quite similar to those of normal ileum.
Measurements of intestinal permeability using low molecular weight polyethylene glycols (PEG 400). I. Chemical analysis and biological properties of PEG 400.
A new approach to the measurement of intestinal permeability in man has been developed, using low molecular weight polyethylene glycol (PEG 400) as probe molecules. PEG 400 (range of molecular weight 232 to 594) is a mixture of water-soluble molecules of different sizes which can be extracted readily from biological fluids and analyzed by gas-liquid chromatography. PEG 400 is nontoxic, not degraded by intestinal bacteria, not metabolized after absorption, and rapidly excreted in urine. The different-sized molecular components cross the intestinal epithelium at different rates, allowing characterization of the passive permeability properties of the mucosa.
Measurements of intestinal permeability using low molecular weight polyethylene glycols (PEG 400). II. Application to normal and abnormal permeability states in man and animals.
A new approach to the measurement of intestinal permeability using low molecular weight polyethylene glycols (PEG 400) has been applied to the study of normal and abnormal permeability states in man and animals. Successful assessments of gastric, jejunal, ileal, and colonic permeability suggest that the technique has application to any area of the gastrointestinal tract. The method has shown that bile acids alter mucosal permeability in the stomach and colon and that celiac sprue is associated with decreased intestinal permeability. These examples illustrate the potential of the technique for studying the function of diseases intestine in man.
Inhibition of water absorption by ricinoleic acid. Evidence against hormonal mediation of the effect.
In three dogs, each with a jejunal and an ileal Thiry-Vella loop, the isolated segments were perfused with isotonic electrolyte solutions (control) for 90 min. One loop was then perfused with 5mM ricinoleic acid for an additional 90 min, while the other loop was perfused with the control solution. Loops perfused with ricinoleic acid all showed reduced fluid absorption. Perfusion of one loop with ricinoleic acid produced no changes in fluid absorption from the loop perfused with the control solution. In other experiments, 4 Ivy dog units (IDU) per kg per hr of cholecystokinin (CCK) produced no change in water movement in loopd perfused with control solution or recinoleic acid. These experiments suggest that the effect of ricinoleic acid on intestinal water transport is not mediated through the release of a circulating humoral substance.
Letter: A further look at laxatives.
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Ricinoleic acid (castor oil) alters intestinal surface structure. A scanning electronmiscroscopic study.
To determine if sodium ricinoleate, the active principle of castor oil, alters mucosal surface structure of the small intestine, rabbit ileum was perfused with isotonic buffer or buffer containing 10 mM of sodium ricinoleate. Mucosal biopsies were examined by scanning electron microscopy. Sodium ricinoleate produced deep clefts or holes at the tips of villi, and at the bases of these clefts unusual cells could be resolved. The microvillus surface of the intestine was also altered at the tips and sides of villi. Microvilli were clumped into "tufts" with numerous intervening "cracks" appearing on the surface. These changes may relate to the well-documented capacity of ricinoleate and dietary long-chain fatty acids to evoke fluid secretion in the intestine. The findings thus pertain to the pharmacology of castor oil and the pathophysiology of steatorrheal disease.
Ricinoleic acid effects on rabbit intestine: an ultrastructural study.
In fasting rabbits, segments of ileum and colon were perfused with ricinoleic acid. This fatty acid is the active principle of castor oil and stimulates intestinal fluid secretion. Biopsies taken from perfused segments were examined by electron microscopy after staining with lanthanum hydroxide and ruthenium red. These stains, which typically bind to extracellular surfaces, were used to assess the integrity of junctional zones between cells. In this study, ricinoleate did not alter ruthenium or lanthanum staining in junctional areas, a finding suggesting that ricinoleate does not cause fluid secretion by selectively disrupting these areas.
Quantification of carcinoembryonic antigen-like activities in normal, human gastrointestinal secretions.
The secretion of carcinoembryonic antigen-like (CEA-like) material into the gastrointestinal tract of 28 fasting normal men was quantified by using intestinal perfusion techniques. CEA-like material was recovered from all levels of the gastrointestinal tract. The highest secretory rate was in the colon (mean +/- SE, 2.41 +/- 2.0 mug/minute per colon), followed by pancreatobiliary secretion and pancreatic secretion. The secretory rate from the stomach, duodenum, jejunum, and ileum was less than 20 ng/minute. After perchloric acid extraction, the CEA-like material from the colon had the same chromatographic and radioimmunologic properties as [125I] CEA. These data suggest that the CEA-like material is normally secreted into the gastrointestinal tract and particularly into the colon.
Ricinoleic acid: current view of an ancient oil.
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Postoperative reflux gastritis.
The chief clinical features of forty-nine patients with the syndrome of reflux "alkaline" gastritis were epigastric pain, bilious vomiting, anemia, and the dumping syndrome. Separation of the symptoms of this syndrome from the symptoms of a multitude of other postgastrectomy syndromes is difficult, being complicated by a high incidence of emotional instability in these patients. Endoscopy remains the mainstay in diagnosis; among the characteristic endoscopic features are adherent mucus, edema, mucosal friability, and erosions, most severe on the gastric aspect of the stoma. The surgical treatment of choice is Roux-en-Y gastrojejunostomy accompanied by vagectomy.
Diarrhea: pathogenesis and diagnostic techniques.
Daily fecal weight is the feature most useful in defining diarrhea, as normal weights for various societies are known. Diarrhea is associated with increased fecal water excretion, with heightened sensitivity of the rectal mucosa, and with exudation of mucus. It occurs acutely, as in gastroenteritis, bacterial dysenteries, and parasitic infections, and chronically, as in functional disorders, malabsorption syndromes, and inflammatory bowel disease. Many seemingly unrelated diseases can also cause diarrhea. The patient's history as well as macroscopic, microscopic, and chemical analysis of stools will offer major clues to the cause of the ciarrhea.
Control of gastric emptying by osmolality of duodenal contents in man.
During the steady state perfusion of the duodenum, recovery of a duodenal marker (polyethylene glycol 4000) can be used to quantify intraduodenal volumes. We used this technique to measure and time the recovery from the duodenum of a second nonabsorbable marker, phenol red. When liquid test meals containing phenol red were placed in the stomach, the rate of gastric emptying could be quantified from the appearance of the maker in the duodenum. The osmolality of either test meal or duodenal perfusates was then varied so that the osmotic control of gastric emptying could be examined. Gastric emptying was fastest when duodenal contents were isotonic; nonisotonic duodenal contents slowed emptying whether these conditions were achieved by nonisotonic duodenal perfusates or by emptying of a nonisotonic test meal. However, nonisotonic solutions in the stomach and in the jejunum did not slow gastric emptying, so long as duodenal contents were isotonic. Osomoreceptors, which slow gastric emptying, are present in the duodenum but not in the jejunum or stomach.