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Biomedical subjects

S F Phillips

Publications and source records attributed to S F Phillips.

At least 199 records · Page 11Linked to original sources

Diarrhoea after continent ileostomy.

To determine the nature and frequency of malabsorption in patients with continent ileostomies, faeces and urine from 42 patients with ileal pouches and from 19 patients with conventional ileostomies were analysed and compared. The patients with conventional ileostomy were matched with patients with ileal pouches. Thirteen of the patients with pouches were found to have excessive faecal volumes which were accompanied by increased faecal losses of electrolytes, nitrogen, and fat, and by decreased vitamin B12 uptake. The remaining patients with continent ileostomies had faecal and urinary outputs which were similar to those of patients with conventional ileostomies. Thus, evidence of malabsorption was found in approximately 30% of this group of patients with continent ileostomies.

Adult↗

Canine jejunal absorption and transit during interdigestive and digestive motor states.

To determine whether absorption varies during interdigestive and digestive motor states, an isolated, 75-cm segment of jejunum was perfused in each of five dogs with an isosmolar solution of 130 mM glucose, 80 mM NaCl, and [3H]polyethylene glycol (PEG). Effluent was collected from the distal stoma during 10-min intervals. Electrical activity of the segment was recorded concurrently. Transit times were assessed with boluses of [14C]-PEG. The dogs were studied during phase I, phase II, and phase III of the interdigestive myoelectric complex and also after a 200-g meal of liver. Absorption during fasting was greatest during phase I and least during phase III of the interdigestive myoelectric complex; feeding enhanced absorption over that seen during any phase of fasting. Transit was slowest in phase I of fasting and most rapid during phase III; transits during phase II of fasting and after feeding were roughly equal. Using indicator-dilution calculations, static volumes were greatest and mean flows slowest during phase I. Thus, jejunal absorption during fasting decreased as transit increased sequentially with the interdigestive myoelectric phases. However, after feeding, although transit time was similar to phase II, absorption was greater.

Action Potentials↗

Myoelectric and motor patterns of continent pouch and conventional ileostomy.

Our aim was to compare the myoelectrical and motor properties of the continent ileal pouch of 19 patients with those of the terminal ileum of six patients with Brooke ileostomy. The undistended ileum in both types of ileostomy exhibited pacesetter potentials at a mean frequency of 9.1 cycles per minute during fasting upon which were superimposed the cyclic bursts of action potentials and attendant contractions characteristic of the interdigestive state. Both types of ileostomy also accommodated to distention, with intraluminal pressure being kept low as the ileum filled. However, the amplitudes of the changes in intraluminal pressure present in the pouch were less than those present in the Brooke ileum both before and during distention, and the volumes to which the ileum could be distended were far greater in the patients with ileal pouches than in those with the Brooke ileostomy. Feeding did not alter the responses to distention of either type of ileostomy. We conclude that the electrical and motor patterns of the undistended ileum are similar in both types of ileostomy, but that the anatomic and motor properties of the pouch allow it to accept far larger intraluminal volumes both during fasting and after feeding.

Action Potentials↗

Absorption from the jejunum is increased by forward and backward pacing.

In 4 dogs a 75-cm segment of jejunum was isolated from the intestinal stream. Stimulating electrodes were implanted at each end of the segment and recording electrodes at intervals between. The two ends of the segment were fashioned as stomas on the anterior abdominal wall. After recovery, the electrical activity of the segment was continuously recorded, whilst a solution of 100 mmol/l glucose and 90 mmol/l NaCl was infused into the proximal stoma at 2.9 ml/min. Effluent from the distal stoma was collected in 5-min aliquots for three consecutive 30-min periods. In the second period electrical stimuli were given via either the proximal or the distal bipolar electrodes to entrain pacesetter potentials. Both forward and backward electrical pacing decreased the output of water, glucose and sodium from the jejunal segment, but the decrease was significantly greater with backward pacing. We conclude that pacing a segment of jejunum backwards with electrical stimuli produces a greater increase in absorption from the segment than pacing it forwards, a finding which has therapeutic implications in patients with the short bowel syndrome.

Animals↗

Absorption of nutrients in lactase deficiency.

The influence of malabsorption of lactose, as a result of primary lactase deficiency, on the absorption of the nutrients in milk was tested in four healthy controls and four subjects with lactase deficiency. An ileal perfusion technique was used to quantify arrival in the ileum of nutrients and a nonabsorbable marker (polyethylene glycol, PEG 4000) ingested as a test meal of milk. The meal was 250 ml of whole milk or milk in which the lactose had been hydrolyzed to glucose and galactose. In the fasting state, ileal flow of volume, protein, carbohydrate, and electrolytes was small and not different in controls and lactase-deficient subjects. Ileal flow increased in all subjects after the test meal of milk; more fluid and nutrient was recovered from the ileum in lactase-deficient subjects after whole milk than in control subjects or in lactase deficiency after hydrolyzed milk. Two deficient subjects showed marked malabsorption of lactose (35 and 50%); two did not. Protein, calcium, magnesium, and phosphorus were also recovered from the ileum in greater quantities in lactase deficients after whole milk. However, apart from decreased absorption of lactose, the nutritional consequences of malabsorption in association with primary lactase deficiency in adults are probably minimal.

Adult↗

Colonic absorption of unconjugated bile acids: perfusion studies in man.

Colonic absorption of three major unconjugated bile acids--cholate, chenodeoxycholate, and deoxycholate--was measured under steady-state conditions using a technique of colonic perfusion in healthy volunteers. Aqueous solutions at pH 8.0 and varying in concentration from 1 mM to 10 mM were used. The rate of chenodeoxycholate absorption averaged nine times that of cholate absorption; deoxycholate absorption was somewhat less than that of chenodeoxycholate absorption, averaging six times that of cholate. At concentrations below 5 mM, the rate of absorption of bile acids was directly proportional to concentration, so that "clearance" could be calculated. Clearance values for a 1-mM solution (ml/min/colon, mean +/- SE) were: chenodeoxycholate, 9.84 +/- 1.0; deoxycholate, 7.0 +/- 1; and cholate, 0.82 +/- 0.10. Since absorption was proportional to concentration in the lumen, and was more rapid for the dihydroxy acids, the major mechanism of absorption was thought to be passive nonionic diffusion. Maximal rates of bile acid absorption were calculated from a 1-mM solution and found to be as high as 4.2 g/day for chenodeoxycholate, 3.2 g/day for deoxycholate, and 0.5 g/day for cholate, and the rate would be still greater for more concentrated solutions. Colonic absorption may contribute significantly to conservation of the dihydroxy bile acid pool, especially in conditions of bile acid malabsorption.

Bile Acids and Salts↗

Effect of molecular structure on bile acid-induced alterations in absorptive function, permeability, and morphology in the perfused rabbit colon.

An in vivo intestinal perfusion system was used to study the effects of different bile acids on fluid secretion, mucosal permeability, and mucosal morphology in the rabbit colon. To define the structure-activity relationships of the bile acids, nine unconjugated bile acids were used, varying only in the number (two or three) or position (3, 7, or 12 or various combinations) of hydroxy or keto nuclear substituents. Results showed that bile acids with two hydroxy groups in the alpha configuration at the 3,7 position, 3,12 position, or 7,12 position induced fluid secretion, increased mucosal permeability, and produced mucosal damage as assessed by light and scanning electron microscopy and quantitated by DNA loss during perfusion. Replacement of hydroxy groups by keto groups or a change from alpha to beta configuration for the hydroxylic substituent in the 7 position abolished all three activities. Trisubstituted derivatives, whether hydroxy or keto, did not affect fluid secretion permeability or cause mucosal damage. These studies indicate that of the major primary and secondary bile acids in man, only deoxycholic and chenodeoxycholic acids alter colonic structure and function in the rabbit. They show further that the cathartic effects of bile acids have specific structural requirements; and they show that bile acid-induced secretion was invariably associated with increased mucosal permeability and epitheliolysis.

Animals↗

Pancreatic insufficiency and Ménétrier's disease. Report of a case with clinical response to pancreatic enzyme replacement.

A patient with exocrine pancreatic insufficiency and hypoalbuminemic edema was shown also to have a protein-losing gastropathy secondary to giant hypertrophic gastritis (Ménétrier's disease). Despite continuation of excessive gastric protein loss, the manifestations of hypoproteinemia were reversed by oral pancreatic enzyme replacement therapy. We speculate that impaired intraluminal proteolysis exaggerated the consequences of gastric protein loss.

Gastritis↗

Increased canine jejunal absorption of water, glucose, and sodium with intestinal pacing.

Our aim was to determine if pacing a segment of jejunum backwards with electrical stimuli could increase absorption from it. In four dogs, 75-cm loops of jejunum were isolated from the intestinal stream. After recovery, fluid was infused into the proximal stoma of the loop and effluent collected from the distal stoma for three consecutive 30-min periods. In the second period electrical stimuli were applied to the distal end of the loop to drive the pacesetter potentials of the loop, hence its contractions, backwards. The output of water, glucose, and sodium from the loop was decreased, and the transit of content through the loop was slowed during backward pacing. We conclude that pacing a segment of jejunum backwards with electrical stimuli enhances absorption of water, glucose, and sodium from that segment.

Animals↗

Chronic diarrhea. A practical approach.

Many patients who present with chronic diarrhea are not found to have an important organic disease. Most will have "functional" diarrhea. The history, the physical examination and the initial laboratory tests should lead to a provisional diagnosis, with respect to the organic or functional origin, and the location of disease in the small or the large bowel. Specific tests are then done to define particular organic causes of which malabsorption, inflammatory bowel diseases, carcinoma of the large bowel, parasitic infections, and metabolic disorders are most common. Patients with suspected functional diarrhea should be investigated at least by stool analysis, proctosigmoidoscopy, and barium enema. Functional diarrhea is common and these patients are no less susceptible to severe disease than is the rest of the population.

Adult↗

Stimulation of adenylate cyclase in homogenates of isolated intestinal epithelial cells from hamsters. Effects of gastrointestinal hormones, prostaglandins, and deoxycholic and ricinoleic acids.

The mechanism by which intestinal secretagogues evoke fluid secretion in the small bowel and colon has been suggested to involve mucosal adenylate cyclase. Adenylate cyclase activity was assayed by conversion of [32P]ATP to [32P]cyclic AMP in a system of pure epithelial cells isolated from the small intestine of the hamster by vibration in buffer. Several gastrointestinal hormones were tested for their capacity to stimulate adenylate cyclase; vasoactive intestinal peptide and impure cholecystokinin-pancreozymin (but not the 99% pure preparation or pure cholecystokinin octapeptide) were potent stimuli, but pentagastrin, glucagon, secretin, and gastric inhibitory peptide were impotent. Two prostaglandins, PGE1 and PGE2, were potent stimuli of adenylate cyclase. Two other compounds that provoke intestinal secretion of fluid, deoxycholic acid and ricinoleic acid (castor oil), were ineffective stimuli of adenylate cyclase. These experiments do not support a clear-cut relationship between a compound's ability to stimulate adenylate cylase and its activity as an intestinal secretagogue.

Adenylyl Cyclases↗

Rabbit ileal mucosa exposed to fatty acids, bile acids, and other secretagogues. Scanning electron microscopic appearances.

Segments of rabbit ileum were examined by scanning electron microscopy (SEM) after exposure to various compounds known to stimulate fluid secretion in the small intestine. After perfusion with ricinoleate (castor oil) at a 10 mM concentration, striking changes were observed at villus tips and on the apicolateral surfaces of villi; erosions at tips were confirmed by light microscopy of the same pieces of tissue examined by SEM. The appearances after ricinoleate were reversed in part during perfusion with control buffer for 2 hr. Statistical comparisons between control perfused, treated, and reversal tissues showed that the "damage" produced by ricinoleate, and its reversal, was significant statistically. Tissues treated with other intestinal secretagogues, oleic acid (10 mM), deoxycholic acid (4 mM), cholic acid (4 mM), dioctyl sodium sulfosuccinate (6 mM), and cholera toxin (1 microgram/ml) also showed surface changes by SEM. Fluid secretion, produced by an osmotic agent (mannitol) was not associated with "damage." Changes in structure of the mucosal surface after exposure to intestinal secretagogues should be considered as one possible mechanism of impaired fluid transport.

Animals↗