Biomedical subjects

J S Fordtran

Publications and source records attributed to J S Fordtran.

At least 91 records · Page 5Linked to original sources

PubMed1982

Starch blockers--their effect on calorie absorption from a high-starch meal.

It has been known for more than 25 years that certain plant foods, such as kidney beans and wheat, contain a substance that inhibits the activity of salivary and pancreatic amylase. More recently, this antiamylase has been purified and marketed for use in weight control under the generic name "starch blockers." Although this approach to weight control is highly popular, it has never been shown whether starch-blocker tablets actually reduce the absorption of calories from starch. Using a one-day calorie-balance technique and a high-starch (100 g) meal (spaghetti, tomato sauce, and bread), we measured the excretion of fecal calories after normal subjects had taken either placebo or starch-blocker tablets. If the starch-blocker tablets had prevented the digestion of starch, fecal calorie excretion should have increased by 400 kcal. However, fecal calorie excretion was the same on the two test days (mean +/- S.E.M., 80 +/- 4 as compared with 78 +/- 2). We conclude that starch-blocker tablets do not inhibit the digestion and absorption of starch calories in human beings.

Adult↗

PubMed1982

A report of five patients with large-volume secretory diarrhea but no evidence of endocrine tumor or laxative abuse.

The purpose of this paper is to report five patients with chronic secretory diarrhea (maximum stool volume greater than 1 liter per day, duration 6 weeks to 8 years) in whom we could find no evidence of an endocrine tumor or of surreptitious laxative ingestion. All except one had severe hypokalemia. There was apparent improvement after treatment with prednisone in two patients and loperamide in one. The diarrhea resolved spontaneously in three patients and has undergone several temporary remissions in one patient. The last patient died after a severe unremitting illness. Extensive investigations failed to establish the etiology, but intestinal perfusion (carried out in four of the five patients) revealed secretion or abnormally low absorption of water and electrolytes in the jejunum and abnormally low absorption in the colon. The management of patients with chronic watery diarrhea is discussed.

Adult↗

PubMed1982

Studies of the mechanism of the antidiarrheal effect of codeine.

To determine whether the antidiarrheal action of opiate drugs in humans is due to enhanced intestinal absorption rates, as suggested by recent experiments in animals, or is due to altered intestinal motility, as traditionally thought, we studied the effect of therapeutic doses of codeine on experimental diarrhea and on the rate of intestinal absorption of water and electrolytes in normal human subjects. Our results show that codeine (30-60 mg i.m.) markedly reduced stool volume during experimental diarrhea induced by rapid intragastric infusion of a balanced electrolyte solution. There was, however, no evidence that codeine stimulated the rate of intestinal absorption in the gut as a whole or in any segment of the gastrointestinal tract, either in the basal state or when absorption rates were reduced by intravenous infusion of vasoactive intestinal polypeptide. We also measured segmental transit times to determine whether and where codeine delayed the passage of fluid through the intestine. Codeine caused a marked slowing of fluid movement through the jejunum, but had no effect on the movement of fluid through the ileum or colon. In other studies, we found that the opiate antagonist naloxone did not significantly affect water or electrolyte absorption rates in the jejunum or ileum. We conclude (a) that therapeutic doses of codeine increase net intestinal absorption (and thereby reduce stool volume) by increasing the contact time of luminal fluid with mucosal cells, not by increasing the rate of absorption by the mucosal cells; and (b) that endogenous opiates do not regulate intestinal absorption in humans.

Adult↗

PubMed1982

Permeability characteristics of human jejunum, ileum, proximal colon and distal colon: results of potential difference measurements and unidirectional fluxes.

In order to assess the passive permeability characteristics of the human intestine in vivo, we measured potential difference in the jejunum, ileum, proximal colon, and distal colon during perfusion of various test solutions that were designed to establish chemical gradients for sodium or chloride, or both or neither. In addition, unidirectional fluxes of sodium and chloride were measured in 30-cm segments of the jejunum and ileum and entire colon during perfusion of balanced electrolyte solution. These studies indicate that there are marked differences in the pathways for passive ion movement in the areas of the intestine studied. In the jejunum, this pathway appears to be highly permeable to both sodium and chloride with modest cation selectivity. In the ileum this pathway is much more cation selective, predominantly because of a relative impermeability to chloride. In the colon, on the other hand, these passive pathways appear to be more anion than cation selective. The implication of these results for normal transport physiology are discussed.

Action Potentials↗

PubMed1982

Ox bile treatment of severe steatorrhea in an ileectomy-ileostomy patient.

Bile salt therapy is not used in patients with steatorrhea due to bile salt deficiency because of fear that severe diarrhea would be caused or exacerbated. We report a patient who previously had had colectomy, partial ileectomy, and ileostomy for Crohn's disease. She had severe steatorrhea due to bile salt deficiency and severe diarrhea (the latter apparently due to fatty acid inhibition of electrolyte and water absorption). The diarrhea was improved by loperamide, but severe steatorrhea and malnutrition persisted. The steatorrhea and malnutrition were corrected by ox bile, without an increase in diarrhea. Presumably, the deleterious effect of bile salts per se on small bowel absorption of water and electrolytes was mitigated by correction of fat malabsorption. At least in this patient, bile salt therapy was highly beneficial.

Bile Acids and Salts↗

PubMed1981

The radiological diagnosis of gallbladder disease. An imaging symposium.

Changes in the radiological diagnosis of gallbladder disease are occurring at a remarkable rate. In this symposium, several recognized authorities place the various diagnostic modalities and their interrelation in modern perspective. The present and future roles of oral cholecystography and intravenous cholangiography, the radiological diagnosis of chronic acalculous cholecystitis, and the use of ultrasonography and cholescintigraphy are analyzed.

Acute Disease↗

PubMed1981

Jejunal and ileal adaptation to alterations in dietary calcium: changes in calcium and magnesium absorption and pathogenetic role of parathyroid hormone and 1,25-dihydroxyvitamin D.

Previous balance studies have shown that fractional calcium absorption is increased by a low and reduced by a high calcium diet. The present studies were done to determine which segment of the small intestine is most sensitive to alterations in dietary calcium, and to see if dietary calcium intake has an effect on the intestinal absorption of another divalent cation, magnesium. Absorption was measured during constant perfusion of 30-cm segments of jejunum and ileum of normal subjects after 4 or 8 wk of a high (1,900 mg/d) or a low (20 mg/d) calcium diet. We found that calcium absorption rate was higher when subjects had been on a low than when they had been on a high calcium diet; the ileum responded more rapidly and more completely than the jejunum. Similar results were obtained with magnesium, but only the difference in the ileum was statistically significant. Sodium and xylose absorption were not influenced by dietary calcium intake. The serum concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D were higher on the low than on the high calcium diet. We conclude that the ileum is more sensitive than the jejunum to changes in dietary calcium intake, and that ileal adaptation probably plays a major role in protecting the body against a deficiency or excess of body calcium that otherwise would occur when dietary calcium is abnormally low or high. Calcium intake influences ileal magnesium absorption in a similar fashion; it is not known whether or not this serves a protective function. Our data are compatible with the concept that adaptation to dietary calcium intake is mediated by changes in the serum concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D.

Adaptation, Physiological↗

PubMed1981

Effect of vasoactive intestinal polypeptide on active and passive transport in the human jejunum.

The effect of intravenous vasoactive intestinal polypeptide (VIP) on normal transport mechanisms in the human jejunum in vivo was examined with the triple-lumen, steady-state perfusion technique. By using special test solutions that revealed different aspects of jejunal transport, we were able to evaluate the effect of VIP on specific transport processes, such as active bicarbonate absorption, active chloride secretion, and passive absorption or secretion of sodium chloride. At an infusion rate of 200 pmol/kg per h, VIP inhibited active bicarbonate absorption by approximately 42%, stimulated active chloride secretion to a slight extent, and slightly reduced passive sodium chloride absorption. A larger dose of VIP, 400 pmol/kg per h, had essentially the same effect on active bicarbonate absorption and active chloride secretion, but it markedly depressed passive sodium chloride absorption and also inhibited passive secretion induced by mannitol. VIP reduced the lumen-to-plasma unidirectional sodium and chloride flux rates, while the plasma-to-lumen flux rates were decreased to a lesser extent or remained unchanged. The potential difference became more lumen-negative with VIP, but the sodium diffusion and glucose-stimulated potential were not affected. We conclude that the major effect of VIP in the human jejunum is to decrease the normal absorption of water and electrolytes--not only active bicarbonate-mediated absorption, but also the passive absorption in response to osmotic forces generated by active or facilitated absorptive processes. Although an increase in chloride secretion does occur, this does not appear to be of major importance.

Adult↗

PubMed1980

Effect of 1,25-(OH)2D3 on jejunal absorption of magnesium in patients with chronic renal disease.

These studies were performed to see if jejunal malabsorption of magnesium in patients with chronic renal disease was influenced by therapy with 1 alpha, 25-dihydroxyvitamin D3 [1,25-(OH)2D3; 2 microgram/day by mouth for 7 days]. This treatment restored normal serum concentrations of the vitamin D metabolite from 0.9 +/- 0.2 to 4.2 +/- 0.6 ng/dl. Jejunal absorption of magnesium, measured by a triple-lumen constant-perfusion technique, was enhanced in each of the seven patients by this therapy. The mean value rose from 0.04 +/- 0.02 to 0.13 +/- 0.02 mmol . 30 cm-1 . h-1. This last value is similar to the magnesium absorption rate in untreated normal subjects. These results demonstrate that magnesium absorption in the human jejunum is dependent on vitamin D, and they show that 1 alpha,25-dihydroxyvitamin D3 therapy in patients with chronic renal failure is associated with an enhanced jejunal absorption of magnesium.

Adult↗

PubMed1980

Active chloride secretion in the normal human jejunum.

To determine whether the small intestine normally secretes fluid, it would be necessary to reduce or inhibit the greater absorptive processes that would otherwise mask such secretion if present. To do this, we perfused bicarbonate-free solutions in the jejunum of normal subjects, because it has been shown that active absorption from this part of the human small intestine is dependent on luminal bicarbonate. We found that the jejunum did secrete sodium chloride and water when isotonic bicarbonate-free solutions were perfused. Further studies revealed that the sodium secretion was passive, but that chloride was secreted against an electrochemical gradient and that observed chloride flux ratios did not agree with the flux ratios calculated for passive chloride movement. We conclude, therefore, that the normal jejunum actively secretes chloride, but that this is masked by greater absorptive processes when balanced electrolyte solutions are perfused. The rate of this active chloride secretion may be one of the factors that regulate the rate of fluid absorption in the normal human intestine.

Bicarbonates↗

PubMed1980

Influence of glucose, fructose, and water movement on calcium absorption in the jejunum.

The first experiment demonstrated that glucose stimulated calcium absorption. Possible mechanisms include: (a) glucose stimulation of active calcium absorption, (b) glucose stimulation of water absorption with enhanced calcium absorption by solvent drag, or (c) glucose stimulation of water absorption caused an increased luminal calcium concentration with resultant increased active and/or passive calcium absorption. In a second experiment, neither glucose, fructose of water absorption stimulated calcium absorption when luminal calcium concentration was maintained at a constant level. These results suggest: (a) glucose and fructose indirectly enhance calcium absorption via an effect on water movement, (b) water absorption enhances calcium absorption by virtue of concentrating unabsorbed calcium within the intestinal lumen, not by solvent drag, and (c) bulk water movement and passive calcium ion movement take place via separate channels.

Biological Transport↗

PubMed1980

Chronic diarrhea of unknown origin.

We studied 27 patients with severe chronic diarrhea for which extensive investigations carried out at other institutions had failed to reveal a diagnosis. They were studied by standard diagnostic methods as well as by careful fecal analysis and intestinal perfusion. If they were incontinent of feces, anal sphincter function tests were performed. Although many were suspected of having pancreatic cholera syndrome, this diagnosis could not be established in a single patient. The most common diagnosis that could be established was surreptitious ingestion of drugs (laxatives in 7 patients and diuretics in 2). Other specific diagnoses included ulcerative colitis in 2 patients, allergy to beef in 1, and bacterial overgrowth of the small intestine in 1. Thus, we were able to establish a specific diagnosis in 13 patients. Of the remaining 14 patients, 8 had findings suggestive of irritable bowel syndrome, and 2 others had anal sphincter dysfunction as the major cause of their disability. The other 4 undiagnosed patients had severe secretory (3 patients) or osmotic (1 patient) diarrhea. Follow-up interviews at 6 mo-6 yr failed to reveal evidence of a cause for diarrhea that had been overlooked during our studies. The diagnostic approach to patients with unexplained diarrhea is discussed. The importance of a search for surreptitious drug ingestion and accurate measurement of bowel movement frequency and stool weight is emphasized.

Adult↗

PubMed1980

Acute effect of diphenoxylate with atropine (Lomotil) in patients with chronic diarrhea and fecal incontinence.

Fifteen patients with chronic diarrhea and fecal incontinence were admitted to a clinical research center and treated for 3 days with either placebo or diphenoxylate with atropine (Lomotil). The patients were then crossed over to the alternate medication. Lomotil had no effect on rectal or anal sphincter pressure or on continence for saline that had been infused into the rectum. However, Lomotil therapy reduced average stool frequency (from 4.9 to 2.6 times/day) and average stool weight (from 460 to 256 g/day). These results suggest that temporary or intermittent therapy with Lomotil and related drugs might benefit patients with chronic diarrhea and fecal incontinence. They should do this by virtue of a reduction in stool frequency and stool volume, without a deleterious effect on the defense mechanisms against incontinence.

Adult↗

PubMed1980

Effect of VIP infusion in water and ion transport in the human jejunum.

Infusion of vasoactive intestinal polypeptide (VIP) is known to cause intestinal secretion in animal models. The present study was designed to answer the question whether VIP has a similar effect on the human intestine. Pure porcine VIP was administered by constant i.v. infusion to healthy subjects while their jejunum was perfused with a plasma-like electrolyte solution. At the lowest VIP infusion rate (100 pmol/kg/hr), plasma VIP levels rose two- to four-fold, and there was an increase in the transmucosal potential difference but no change in sodium chloride absorption. At higher VIP infusion rates (200 and 400 pmol/kg/hr), VIP plasma concentrations rose to levels commonly observed in patients with pancreatic cholera syndrome. At these levels VIP caused a dose-dependent decrease of water and sodium absorption. Chloride absorption changed to secretion, while bicarbonate movement remained completely unaffected. Chloride secretion was active, since it occurred against an electrical and chemical gradient. All changes induced by VIP were reversible after discontinuance of VIP infusion. Our observations suggest that elevated levels of circulating VIP are capable of affecting water and ion movement in the human jejunum. They lend support to the hypothesis that high levels of circulating VIP may be a mediator of secretory diarrhea in some patients with pancreatic cholera syndrome.

Adult↗

PubMed1980

Development of a lavage solution associated with minimal water and electrolyte absorption or secretion.

Ingestion of large volumes of a balanced electrolyte solution has previously been shown to be an effective method of cleaning the colon for diagnostic studies. However, in this paper we have shown that total gut perfusion with such a solution results in absorption of 2400 ml water and 375 meq of sodium over 3 hr, which is the approximate time required to clean the colon by this technique. This might be hazardous to patients who are unable to readily excrete a salt and water load. We, therefore, designed a solution containing mainly sodium sulfate that was associated with only trivial amounts of water and sodium absorption or secretion during total gut perfusion. This new solution might be useful in colon cleansing before colonoscopy, barium enema, and surgery. In addition, such a solution may have some therapeutic indications, including bowel cleaning in patients with hepatic encephalopathy or as a rapid washout technique for ingested toxins.

Diarrhea↗

PubMed1980

Inhibition of water and electrolyte absorption by polyethylene glycol (PEG).

Polyethylene glycol (PEG) is commonly used as a nonabsorbable volume marker in intestinal perfusion and flow studies. It has been assumed that PEG does not affect water and electrolyte movement, but this has not been extensively investigated. Using triple-lumen tube perfusion technique, we examined the effect of various PEG concentrations (0, 2, 5, 10, and 20 g/liter) on water and electrolyte absorption by the jejunum and ileum in normal subjects. 14C-labeled PEG served as the nonabsorbable marker in the 0 PEG concentration solution. There was a progressive reduction in water, sodium, and chloride absorption as the concentrations of PEG was increased from 0 to 20 g/liter. Though further studies are necessary to establish the mechanism responsible for this PEG effect, the observed changes in luminal fluid osmolality and electrolyte concentrations suggest that the reduction in absorption most likely results from an osmotic effect rather than an inhibition of active absorption or stimulation of secretion.

Electrolytes↗

PubMed1980

Experience with sham feeding as a test for vagotomy.

Sham feeding is thought to stimulate gastric acid secretion solely via vagal pathways. We evaluated whether sham feeding can be used as a test for vagotomy. From results in 50 nonvagotomized subjects (28 unoperated duodenal ulcer patients and 22 healthy controls), a ratio of sham feeding-stimulated acid output to peak acid output of 0.10 or less was defined as abnormally low (with 95% confidence). The ratio of sham feeding to peak acid output was abnormally low in 28 of 41 (68%) vagotomized duodenal ulcer patients without clinical evidence of recurrent ulcer, suggesting that most of these patients had indeed had an effective reduction in vagal innervation of the stomach. On the other hand, 11 of 15 (73%) vagotomized duodenal ulcer patients with symptomatic, recurrent ulcers had normal ratios of sham feeding to peak acid secretion. That a normal ratio represented an incomplete vagotomy was independently suggested in 5 of these patients; in 1 an intact vagal trunk was confirmed at a second operation; in the other 4, acid secretion fell strikingly after transthoracic vagotomy, which would not have been expected to happen if vagotomy had initially been complete. In 5 vagotomized patients tested on two occasions, the ratio was reasonably reproducible. We conclude that a ratio of sham feeding-stimulated to peak acid output greater than 0.10 after an attempted vagotomy suggests persistent vagal innervation, whereas a ratio of 0.10 or less suggests, with at least 95% confidence, that vagotomy has been successful.

Adult↗

PubMed1980

Effect of sham feeding on gastric acid secretion in healthy subjects and duodenal ulcer patients: evidence for increased basal vagal tone in some ulcer patients.

Sham feeding augments gastric acid secretion by activating efferent vagal pathways to the stomach. If increased vagal activity in the basal state were the cause of increased basal acid secretion in some patients with duodenal ulcer, these patients might be expected to secrete little or no additional acid in response to sham feeding. To test this, we measured basal and sham feeding-stimulated acid secretion (as well as peak pentagastrin-stimulated acid output) in 29 duodenal ulcer patients and 22 healthy subjects. Four ulcer patients who had markedly increased basal acid secretion (basal/peak acid output > 0.30) and normal basal serum gastrin concentrations failed to augment acid secretion in response to sham feeding. On the other hand, patients with marked basal acid hypersection owing to hypergastrinemia (Zollinger-Ellison syndrome) responded to sham feeding with a large increase in acid secretion above basal rates. Every normal subject responded to sham feeding with an increase in acid secretion above basal rates, even when acid secretion had been stimulated by an intravenous pentagastrin infusion before beginning sham feeding. These findings suggest that in some patients with duodenal ulcer (4 of 29 in this study) increased basal acid secretion is caused by increased vagal tone.

Adult↗