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Biomedical subjects

J S Fordtran

Publications and source records attributed to J S Fordtran.

At least 109 records · Page 6Linked to original sources

Selective jejunal hyperabsorption of calcium in absorptive hypercalciuria.

Calcium absorption in the jejunum and ileum of patients with absorptive hypercalciuria was studied by in vivo intestinal perfusion. Net calcium absorption in the jejunum was markedly increased at four luminal calcium concentrations (1 to 20 mM) in the patients with absorptive hypercalciuria when compared to that in normal subjects. In the ileum, net calcium absorption was only slightly increased in the patients with absorptive hypercalciuria. Experiments with radioactive calcium (47Ca) revealed increased unidirectional flux out of the jejunal lumen in the patients but no difference in the unidirectional flux into the lumen, when compared to that in normal control subjects. Net magnesium absorption was normal in the patients. These results suggest that hyperabsorption of calcium in patients with absorptive hypercalciuria is mainly due to enhanced calcium transport in the jejunum and that the defect is specific for calcium since magnesium is absorbed normally.

Adult↗

Effect of ouabain on Na,K-ATPase and electrolyte transport in the dog ileum in vivo.

It is currently believed that the rate and direction of sodium transport in the small intestine may be regulated by the activity of Na,K-ATPase in the basolateral cell membrane. We tested this hypothesis by selectively infusing ouabain, a known inhibitor of Na,K-ATPase, into the mesenteric artery supplying a perfused loop of ileum in 18 dogs. Before ouabain infusion there were significant correlations between the activity of Na,K-ATPase and net and lumen to plasma fluxes of sodium and chloride. After ouabain, there was no significant change in sodium and chloride transport, unidirectional fluxes or transmucosal potential difference, despite a 50% reduction in Na,K-ATPase activity. Furthermore, there was no significant correlation between Na,K-ATPase activity and sodium or chloride transport after ouabain. The only statistically significant effect of ouabain infusion was a reduction in the rate of bicarbonate secretion. Thus, the results of our experiments suggest that mucosal Na,K-ATPase is not a rate-limiting step in the absorption of sodium and chloride in the dog ileum, though it may be an important facilitative factor.

Animals↗

Spontaneous secretion from the dog small intestine in vivo.

Forty loops of small intestine in the dog were perfused under control conditions with a balanced electrolyte solution. Most of the loops absorbed sodium and water, but 10 loops were in a state of spontaneous intestinal secretion. Compared to absorbing loops, spontaneously secreting loops exhibited reduced values for lumen-to-plasma fluxes of sodium and chloride and increased values for the plasma-to-lumen fluxes of these ions. Analysis of flux ratios suggested that sodium and chloride were actively scecreted during spontaneous intestinal secretion in the dog. Spontaneous secretion was similar to the secretion induced by CT or VIP, except that the latter were associated with a change in PD whereas the PD in the spontaneously secreting loops was the same as in the spontaneously absorbing loops.

Animals↗

The role of intraluminal junction potentials in the generation of the gastric potential difference in man.

Using flowing isotonic NaCl or flowing molar KCl electrodes, the magnitude of liquid junction potentials between the electrode tip and gastric juice was measured directly, and calculated from electrolyte concentrations in gastric juice according to standard formulas. Gastric transepithelial potential difference was obtained by subtracting the junction potential from the measured gastric potential difference. Junction potentials by direct experiment correlated closely with calculated values. The magnitude of the junction potential was shown to depend on the level of gastric acidity as well as on the nature of the flowing intraluminal electrode. However, transepithelial potential difference was always the same with the two electrode solutions. It is impossible to measure junction potentials with an intraluminal KCl agar electrode, but they must exist because these electrodes did not accurately measure transepithelial potential difference when gastric acidity was high. Pentagastrin caused a transient decline in transepithelial potential difference; this was not observed in patients with pernicious anemia. We conclude that accurate measurement of transepithelial potential difference must include correction for liquid junction potentials, which are sizable when gastric acidity is high. This can best be done with a flowing intraluminal electrode.

Achlorhydria↗

Epidemic gastritis with hypochlorhydria.

Seventeen of 37 healthy volunteers participating in studies of acid secretion and 1 patient with Zollinger-Ellison syndrome became rapidly and profoundly hypochlorhydric. A mild illness with epigastric pain occurred in 9 subjects, usually several days before detection of hypochlorhydria. Gastric mucosal biopsy specimens taken from subjects during hypochlorhydria revealed severe fundal and antral gastritis; however, even when acid secretion was severely depressed, parietal cells were abundant and appeared normal histologically. During hypochlorhydria, gastric permeability to hydrogen, sodium, and lithium was normal in 4 subjects. Serum gastrin concentrations were usually normal, whereas serum pepsinogen concentrations were invariably elevated. Serum parietal cell antibodies were not present. Acid secretion returned to near baseline levels in 14 of 17 subjects after a mean of 126 days (range 53--235); severity of gastritis diminished concurrently in 7 of 10 subjects on whom biopsies were serially performed. An infectious etiology is suspected, although serologic studies and bacterial and conventional viral cultures of stool and gastric juice have not identified a candidate agent.

Achlorhydria↗

On balance.

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Endoscopy↗

Effect of vagotomy in Zollinger-Ellison syndrome.

We evaluated the effect of vagotomy on gastric acid secretion and the clinical course in 3 patients with Zollinger-Ellison syndrome. Basal acid hypersecretion was reduced by 49, 86, and 96%, and peak acid output in response to pentagastrin was reduced by 36, 39, and 71% in the 3 patients. In one patient, 300 mg cimetidine reduced basal acid secretion from 65 to 20 meq/hr before vagotomy; whereas after vagotomy basal acid secretion was reduced from 36 to 0.6 meq/hr by the same dose of cimetidine. One patient has required no antisecretory therapy for 14 yr, whereas 2 patients have also been treated with cimetidine with excellent results. We conclude that vagotomy facilitates control of acid secretion in Zollinger-Ellison syndrome, and we recommend vagotomy and cimetidine rather than total gastrectomy or cimetidine alone for the management of these patients. This combined surgical and medical approach should also allow discovery and removal of isolated tumors in about 10% of patients.

Adult↗

Fecal incontinence in chronic diarrhea. Report of a case with improvement after training with rectally infused saline.

Patients with chronic diarrhea and fecal in continence are unable to retain as much rectally infused saline as patients without incontinence. We explored the effect of training such a patient to retain rectally infused saline. The patient was a 31-yr-old female with chronic diarrhea of obscure etiology who had daily episodes of fecal incontinence which markedly restricted her lifestyle. Training was accomplished by urging the patient to retain as much of a 25-min rectal infusion of 1500 ml saline as possible. After 10 training sessions, the patient increased her ability to hold rectally infused saline almost sevenfold. This increase was well maintained over 10 wk. In spite of continued diarrhea, the patient's incontinence did not recur after the first week of training, and she was able to resume a normal life. Anal sphincter pressure and a test of continence for a solid sphere did not change during or after training. This simple training technique has potential as a treatment for disabling fecal incontinence in patients with chronic diarrhea.

Adult↗

Effect of modified sham feeding on jejunal transport and pancreatic and biliary secretion in man.

Because previous evidence suggested that intestinal secretion was under parasympathetic control, we investigated the effect of modified sham feeding on the intestinal transport of water and electrolytes by jejunal perfusion using a triple lumen tube. By measuring the concentration of amylase, protein, and bile acids entering the intestinal test segment, we were also able to obtain data on the influence of sham feeding on pancreatic and biliary secretion. Gastric contents were aspirated throughout the experiment. Although we observed a clear-cut cephalic phase of gastric acid secretion, sham feeding had no effect on jejunal transport of water and electrolytes or on the rate at which bile acids, protein, or amylase were secreted into the duodenum.

Adult↗

Intestinal secretion induced by vasoactive intestinal polypeptide. A comparison with cholera toxin in the canine jejunum in vivo.

The effect of vasoactive intestinal polypeptide (VIP) on intestinal water and electrolyte transport and transmucosal potential difference was investigated in the dog jejunum in vivo and compared to secretion induced by cholera toxin. Isolated jejunal loops were perfused with a plasma-like electrolyte solution. VIP (0.08 mug/kg per min) was administered directly into the superior mesenteric artery by continuous infusion over 1 h. From a dye dilution method, it was estimated that a mean plasma VIP concentration of 12,460 pg/ml reached the loops. VIP caused secretion of water and electrolytes; for example, chloride: control, 8 mueq/cm per h absorption; VIP, 92 mueq/cm per h secretion. A marked increase in transmucosal potential difference (control, -1.0 mV; VIP, -5.9 mV, lumen negative) occurred within 1 min after starting VIP infusion. Analysis of unidirectional fluxes showed increased plasma-to-lumen flux of sodium and chloride and decreased lumen-to-plasma flux of sodium. Chloride and bicarbonate were actively secreted against an electrochemical gradient. Although sodium secretion occurred down an electrochemical gradient, flux ratio analysis suggested a component of active sodium secretion. VIP caused a slight increase in protein output into the loops; light microscopy revealed capillary dilatation and closed intercellular spaces. The effect of VIP was readily reversible. Except for the delayed onset of secretion, the effect of cholera toxin was qualitatively similar to VIP; however, capillary dilatation and increased protein output were not noted with cholera toxin.

Animals↗

Effect of low-dose propantheline on food-stimulated gastric acid secretion: comparison with an "optimal effective dose" and interaction with cimetidine.

We evaluated the widely held notion that anticholinergic drugs must be used in near toxic doses to inhibit gastric acid secretion effectively. Nine patients with duodenal ulcer were studied after a low dose (15 mg) and after a near toxic dose (averaging 48 mg) of the anticholinergic, propantheline. Mean (+/- S.E.) inhibition of food-stimulated acid secretion was identical with the two doses of propantheline: 29 +/- 10 and 29 +/- 11 per cent, respectively. In addition, when 15 mg of propantheline was combined with the histamine H2-receptor antagonist, cimetidine, acid secretion was suppressed to a greater degree than with either drug alone. A low dose of propantheline is as effective as a near toxic dose in suppressing food-stimulated acid secretion and augments the inhibitory effect of cimetidine.

Adult↗

Healing of duodenal ulcer with an antacid regimen.

To determine whether a large-dose antacid regimen is effective in promoting healing of duodenal ulcer, 74 patients with endoscopically proved duodenal ulcer completed a 28-day double-blind clinical trial comparing such a regimen with an inert placebo. The ulcer healed completely in 28 of the 36 antacid-treated as compared to 17 of the 38 placebo-treated patients (P less than 0.005). The antacid regimen was not more effective than placebo in relieving ulcer symptoms. Presence or absence of symptoms during the fourth treatment week was a poor predictor of presence or absence of an ulcer crater. Ulcers of placebo-treated patients who smoked cigarettes were less likely to heal than those of nonsmokers (P = 0.03). Except for mild diarrhea, no side effects of the antacid regimen were observed. We conclude that a large-dose antacid regimen hastens the healing of duodenal ulcer.

Administration, Oral↗

Intractable diarrhea. Intestinal perfusion studies and plasma VIP concentrations in patients with pancreatic cholera syndrome and surreptitious ingestion of laxatives and diuretics.

Small-intestinal perfusion studies with a triple-lumen tube were performed in the jejunum and ileum of 11 patients with a presumptive diagnosis of pancreatic cholera syndrome (PCS). Ultimately PCS was proven to be present in only 3 patients, whereas 6 were discovered to be taking either laxatives or diuretics surreptitiously. In 2 of the 11 patients the cause of the diarrhea could not be determined. In PCS the major abnormality which we observed was that the jejunal mucosa secreted rather than absorbed when perfused with a plasma-like solution. By contrast, the ileum of the PCS patients absorbed a plasma-like solution in a normal fashion; however, one patient failed to absorb sodium and chloride when a solution with low (50 mM) sodium chloride concentration was perfused in the ileum. The volume of endogenous fluid was high in both the jejunum and ileum, presumably because of proximal small-intestinal secretion. Glucose stimulated sodium movement in an absorptive direction in each patient. Studies were repeated in one PCS patient after tumor removal, and his intestinal absorption of water and electrolytes was normal. Patients with diarrhea due to surreptitious ingestion of laxatives and diuretics showed normal absorption in the jejunum and ileum. This study shows that proximal small-bowel secretion was the major cause for diarrhea in our 3 patients with PCS. This cannot be a consequence of diarrhea per se since it was not found in patients with long-standing diarrhea due to surrepitious drug ingestion. Small-intestinal perfusion studies may be helpful in the diagnosis and management of selected cases of severe chronic diarrhea. On the other hand, measurement of plasma VIP concentration, especially by methods currently used in the United States, is of little use and may be misleading.

Adult↗

Studies on the role of cephalic-vagal stimulation in the acid secretory response to eating in normal human subjects.

These experiments were performed to determine the importance of cephalic-vagal stimulation in the acid secretory response to eating in normal human subjects. Cephalic stimulation was induced by a modified sham feeding (MSF) technique, during which subjects chewed and expectorated appetizing food. The response to MSF was compared with that to gastric distention with 600 ml NaCl, glucose, or food. In addition, we measured the extent to which cephalic stimulation augments acid secretion that has been stimulated simultaneously by these other mechanisms. Our conclusions are as follows: (a) cephalic stimulation accounts for approximately one-third of the acid secreted when all mechanisms act simultaneously (food-distention plus MSF); (b) within the limits imposed by the maximal secretory capacity, the response to MSF is approximately the same, regardless of whether acid secretion is otherwise unstimulated or is stimulated simultaneously by gastric distention with NaCl, glucose, or food; and (c) gastric distention prolongs the response to cephalic stimulation.

Adult↗