Ulcer complications during short-term therapy of duodenal ulcer with active agents and placebo.
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Anti-Ulcer Agents↗
Biomedical subjects
J S Fordtran
Publications and source records attributed to J S Fordtran.
The absorption of dietary phosphorus and calcium in hemodialysis patients.
Absorption of dietary phosphorus plays a critical role in the development of metabolic bone diseases in patients with chronic renal failure. However, phosphorus absorption is difficult to quantitate in dialysis patients because the dialysis treatments complicate metabolic balance studies. Utilizing a recently developed technique which permits measurement of net absorption of dietary constituents after a single meal, we measured phosphorus absorption in dialysis patients. The following observations were made: A.) Following a meal containing approximately 300 mg phosphorus, mean phosphorus absorption in five hemodialysis patients (with severe vitamin D deficiency) was only slightly less than in matched controls (186 +/- 35 vs. 242 +/- 30). B.) After dialysis patients were treated with 1,25(OH)2-D3, phosphorus absorption increased from 186 +/- 35 to 272 +/- 16 mg (P less than 0.025). C.) The effect of three aluminum containing antacids on phosphorus absorption was studied; each slightly reduced the absorption of phosphorus compared to placebo (P less than 0.01), but there was no significant difference between them. D.) Aluminum hydroxide and calcium carbonate each reduced dietary phosphorus absorption to approximately the same extent. Calcium carbonate ingestion was associated with sharply increased calcium absorption. The absorption of dietary phosphorus is influenced only modestly by 1,25(OH)2-D3 and is inhibited to an equal but only modest degree by various aluminum antacids and by calcium carbonate.
Adult↗
Pathophysiology of chronic diarrhoea: insights derived from intestinal perfusion studies in 31 patients.
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Adult↗
Quantitating the occult.
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Colonic Neoplasms↗
Studies of the antidiarrheal action of clonidine. Effects on motility and intestinal absorption.
Clonidine, an alpha 2-adrenergic agonist, has been reported to stimulate the rate of electrolyte absorption in vitro, to alter intestinal motility in vivo, and to have antidiarrheal effects in animals. Experiments were performed in 8 healthy volunteers in order to evaluate the antidiarrheal effect of clonidine in humans. When diarrhea was induced by intragastric infusion of 2700 ml of balanced electrolyte solution over 90 min, oral administration of 0.3 mg of clonidine reduced the volume of rectal effluent by 48% (from 1233 +/- 62 to 640 +/- 77 ml, p less than 0.001), a clear-cut antidiarrheal effect. Clonidine increased total gut volume significantly (from 987 +/- 91 to 1830 +/- 142 ml, p less than 0.001), suggesting that clonidine exerted its antidiarrheal effect by altering gut motility, i.e., increasing the capacity of the gut and slowing the transit of fluid through the intestine. In other experiments, the net absorption rate of the whole gut during steady state total gut perfusion was measured. The rate of absorption of fluid was transiently stimulated by clonidine by 15% (from 696 +/- 77 to 799 +/- 55 ml/h, p less than 0.02), indicating an additional effect on mucosal cell function. These studies indicate that in this experimental diarrhea model, clonidine has antidiarrheal properties that are due largely to effects on motility of the gut but that clonidine also modestly stimulates the net rate of absorption by intestinal mucosa.
Adult↗
Effect of magnesium on active and passive sodium transport in the human ileum.
The effect of 12.5 mM magnesium chloride on sodium transport in the human ileum in vivo was investigated using segmental perfusion. Choline chloride was used as a control. During perfusion of a balanced electrolyte solution containing isotopes of sodium and chloride, magnesium reduced unidirectional flux of sodium in both directions across the ileum; magnesium had no statistically significant effect on net sodium absorption, on chloride fluxes, or on potential difference. When sodium-free test solutions were infused, magnesium (and calcium) reduced net sodium secretion compared with choline and potassium. These results suggest that magnesium (and calcium) reduce passive sodium movement across ileal mucosa.
Biological Transport↗
Treatment of Zollinger-Ellison syndrome with exploratory laparotomy, proximal gastric vagotomy, and H2-receptor antagonists. A prospective study.
Twenty-two patients with Zollinger-Ellison syndrome were managed by a combined medical and surgical approach. Patients were treated initially with cimetidine or ranitidine. A laparotomy was performed to remove easily resectable tumors and to carry out a proximal gastric vagotomy. Tumors were found in 9 patients (41%) and all visible tumors were removed from 6 of the 9 patients. Fasting serum gastrin concentrations and serum gastrin responses to intravenous secretin were normal 6 wk after surgery in each of the patients from whom all visible tumors were resected and are normal in 4 patients, 6 wk to 5 yr after surgery. Acid secretion was reduced after vagotomy in each patient, even when tumors were not found or completely resected. Thus, vagotomy decreased the acid secretory response to endogenous hypergastrinemia. In addition, vagotomy augmented the inhibitory effect of H2-receptor antagonists on acid secretion. Follow-up has ranged from 6 wk to 6 yr (median, 2 yr). Dosages of cimetidine or ranitidine have been reduced, compared with preoperative amounts, in all but 1 patient. Two patients are taking no antisecretory drugs. Only 3 patients have had occasional symptoms of ulcer disease. Complications such as bleeding, perforation, or obstruction have not occurred in any patient. Endoscopy was performed in all patients to estimate the point prevalence of active ulcers and an ulcer was found in 1 patient. Based on these results, it is our opinion that this combined medical and surgical approach is an effective treatment for patients with Zollinger-Ellison syndrome.
Adolescent↗
An evaluation of the significance of microscopic colitis in patients with chronic diarrhea.
Some patients with chronic idiopathic diarrhea have an apparent nonspecific inflammation of colonic mucosa, even though their colons appear normal by barium enema and colonoscopy. This has been referred to as microscopic colitis. However, the significance of this finding is unclear, because the ability of pathologists to accurately distinguish mild degrees of abnormality has not been established. Furthermore, even if the mucosa of these patients is nonspecifically inflamed, it is not known whether this is associated with deranged colonic function that could contribute to the development of chronic diarrhea. To assess these questions, we first examined colonic biopsy specimens in a blinded fashion, comparing biopsy results from patients with microscopic colitis with biopsy specimens from subjects in two control groups. This analysis revealed that colonic mucosa from six patients with microscopic colitis was in fact abnormal. For example, their mucosa contained an excess of both neutrophiles and round cells in the lamina propria, cryptitis, and reactive changes. These and other differences were statistically significant. Second, colonic absorption, measured by the steady state nonabsorbable marker perfusion method, was severely depressed in the patients. For example, mean water absorption rate was 159 ml/h in normal subjects and was reduced to only 26 ml/h in six patients with microscopic colitis. Results of net and unidirectional electrolyte fluxes and of electrical potential difference suggested that colonic fluid absorption was abnormal because of reduced active and passive sodium and chloride absorption and because of reduced Cl/HCO3 exchange. Small intestinal fluid and electrolyte absorption was abnormally reduced in two of the six patients, suggesting the possibility of coexistent small intestinal involvement in some of these patients. We conclude that nonspecific inflammation of colonic mucosa is associated with a severe reduction of colonic fluid absorption, and that the latter probably contributes to the development of chronic diarrhea.
Adult↗
An evaluation of the importance of gastric acid secretion in the absorption of dietary calcium.
Since calcium solubility is a prerequisite to calcium absorption, and since solubility of calcium is highly pH-dependent, it has been generally assumed that gastric acid secretion and gastric acidity play an important role in the intestinal absorption of calcium from ingested food or calcium salts such as CaCO3. To evaluate this hypothesis, we developed a method wherein net gastrointestinal absorption of calcium can be measured after ingestion of a single meal. A large dose of cimetidine, which markedly reduced gastric acid secretion, had no effect on calcium absorption in normal subjects, and an achlorhydric patient with pernicious anemia absorbed calcium normally. This was true regardless of the major source of dietary calcium (i.e., milk, insoluble calcium carbonate, or soluble calcium citrate). Moreover, calcium absorption after CaCO3 ingestion was the same when intragastric contents were maintained at pH 7.4 (by in vivo titration) as when intragastric pH was 3.0. On the basis of these results, we conclude that gastric acid secretion and gastric acidity do not normally play a role in the absorption of dietary calcium. Other possible mechanisms by which the gastrointestinal tract might solubilize ingested calcium complexes and salts are discussed.
Achlorhydria↗
Gas production after reaction of sodium bicarbonate and hydrochloric acid.
Ingestion of sodium bicarbonate has been implicated as one of the proximate causes of spontaneous gastric rupture. However, the volume and rate of gas released from the reaction of ingested sodium bicarbonate and gastric acid has not been previously studied in detail. We, therefore, developed an in vitro method for measuring gas release after addition of sodium bicarbonate to a solution containing hydrochloric acid. From the results of our studies, we conclude that even though hydrochloric acid and sodium bicarbonate react instantaneously, the resulting gas production is slow, mainly because CO2 produced from the dehydration of carbonic acid dissolves in water and is only slowly released into the gas phase. The major exogenous factors that determine the rate of gas release are the volume of the solution, the quantity of reactants, the air volume over the reaction mixture, the partial pressure of CO2 of the acid solution before the addition of bicarbonate, and the stirring rate. The presence of food, alcohol, and carbonic anhydrase had relatively little if any effect. Based on our results, we believe that ingestion of the recommended dose of sodium bicarbonate (one-half teaspoon) would result in only small amounts of sudden gas release, probably not enough to be an important factor in causing spontaneous gastric rupture. On the other hand, we measured the amount of sodium bicarbonate that people actually select to take for indigestion, and all exceeded the recommended dose. Some people selected doses of bicarbonate that would result in several hundred milliliters of gas release within 3 min; it seems likely that such injudicious ingestion of sodium bicarbonate, if taken when the stomach was distended with air, food, and liquid, could be an important factor in spontaneous gastric rupture.
Bicarbonates↗
Mechanism of the antidiarrheal effect of loperamide.
To determine whether the antidiarrheal effect of loperamide is due to an effect on intestinal motor function or to an acceleration of the rate of absorption by the intestine (as has been suggested recently), we studied absorption during experimental diarrhea produced by the rapid intragastric infusion of electrolyte solution. In studies in which a 2700-ml bolus of electrolyte solution was infused into the stomach over 90 min, loperamide delayed the appearance of rectal effluent in each of 5 subjects and decreased the volume of rectal effluent from 1090 +/- 118 to 770 +/- 73 ml (p = 0.05). When intragastric infusion was continued for 5 h, producing steady-state total gut perfusion, the volume of effluent produced per unit time and the concentration of a nonabsorbable polyethylene glycol marker in rectal effluent was not different with or without loperamide, indicating that loperamide did not alter the rate of absorption by intestinal mucosal cells. Loperamide also had no effect during steady-state perfusion when absorption rates were reduced by intravenous infusion of vasoactive intestinal polypeptide. Loperamide did substantially increase the intraluminal volume of the total gut, from 985 +/- 131 to 1764 +/- 195 ml (p less than 0.02). These results suggest that loperamide exerts its antidiarrheal effect by a change in the motor function of the intestine, which results in increased capacitance of the gut and a delay in the passage of fluid through the intestine. This change in motor function, rather than a change in the rate of absorption by intestinal mucosal cells, is responsible for the antidiarrheal effect of loperamide in our experimental diarrhea model.
Adult↗
Fecal fat concentration in patients with steatorrhea.
We predicted that fecal fat concentration (grams of fat per gram of stool wet weight) would be higher in patients with pancreatic steatorrhea than in those with steatorrhea due to gastrointestinal disease. To evaluate this hypothesis, we examined fecal weight, fecal fat excretion, and fecal fat concentration in 19 patients with steatorrhea due to pancreatic insufficiency and in 31 patients whose steatorrhea was due to various gastrointestinal diseases. There was no consistent difference in the severity of steatorrhea or diarrhea between the two groups of patients. Fecal fat concentration, however, was usually higher in patients with pancreatic insufficiency. Fecal fat concentration may be a useful clue in distinguishing pancreatic steatorrhea from steatorrhea due to gastrointestinal disease.
Celiac Disease↗
Lithium absorption in tight and leaky segments of intestine.
There is significant absorption of Li+ by human jejunum and ileum, but negligible absorption by human colon. Thus, a proximal-to-distal gradient of decreasing Li+ absorption and increasing junctional tightness exists in intestine as well as in renal tubule. For six leaky epithelia the relative permeabilities of K+, Na+, and Li+ by the junctional route are in the sequence PK greater than PNa greater than PLi and all fall within a factor of 2.5. In contrast, for tight epithelia PLi approximately PNa much greater than PK in the amiloride-sensitive channel of the apical membrane, but PK much greater than PLi approximately PNa in the basolateral membrane. The ability of several tight epithelia to sustain nonzero transepithelial Li+ absorption despite this basolateral barrier may be due to Na+/Li+ countertransport at the basolateral membrane, resulting in secondary active transport of Li+ across the epithelium.
Adult↗
Evaluation of chloride/bicarbonate. Exchange in the human colon in vivo.
During perfusion of a plasma-like solution, colonic absorption rate of chloride was much higher than the secretion rate of bicarbonate (34 vs. 3.5 meq/h, respectively). This might suggest that anion exchange (Cl/HCO3) accounts for only a small fraction of total chloride absorption. However, if the colon absorbs as well as secretes bicarbonate, this reasoning would underestimate the magnitude of the anion exchange. To see if the colon absorbs bicarbonate, we perfused a chloride-free solution (which would eliminate bicarbonate secretion via (Cl/HCO3 exchange) and found that the colon absorbed bicarbonate at a rate of 5.1 meq/h. Calculation of electrochemical gradients and measurement of luminal fluid PCO2 indicated that this bicarbonate absorption was mediated passively in response to electrical gradients, rather than via reversed Cl/HCO3 exchange or acid secretion. The combined results of the plasma-like and chloride-free perfusion experiments suggest Cl/HCO3 exchange at a rate of 8.6 meq/h (the sum of bicarbonate movements, 3.5 and 5.1 meq/h, observed in the two experiments). To obtain a second estimate under different experimental conditions, a choline chloride-choline bicarbonate (sodium-free) solution was perfused; with this solution, chloride and bicarbonate absorption dependent on active sodium transport should be eliminated or markedly reduced, and the magnitude of Cl/HCO3 exchange should be revealed. This experiment suggested a Cl/HCO3 exchange rate of 9.3 meq/h, similar to the first estimate. As chloride was absorbed at a rate of 34 meq/h during perfusion of the plasma-like solution, the Cl/HCO3 exchange provides for approximately one-fourth of total chloride absorption.
Absorption↗
Purging and calorie absorption in bulimic patients and normal women.
Self-induced purging with laxatives is common among bulimic persons, who assume that purging reduces intestinal absorption of ingested calories. However, the efficacy of purging in reducing calorie absorption has never been studied, probably because the standard calorie balance procedure is expensive and time consuming. With a recently devised method, calorie absorption during a single day was measured to determine to what extent phenolphthalein or saline purge reduced calorie absorption. In two bulimic patients who regularly used laxatives for weight control and five normal young women, even extreme purging producing 4 to 6 L of diarrhea caused calorie absorption to decrease by only about 12% of calorie intake. The theoretical basis on which laxatives are taken for weight control is unsound.
Adult↗
Absorption of phosphate in the jejunum of patients with chronic renal failure before and after correction of vitamin D deficiency.
To examine the role of vitamin D in human phosphate absorption, we studied patients with chronic renal disease on hemodialysis, before and after correction of vitamin D deficiency. Thirty-centimeter segments of jejunum were perfused with test solutions containing varying concentrations of phosphate; phosphate absorption rate and electrical potential difference were measured. The data reveal that dialysis patients have depressed phosphate absorption, but the degree of this depression is modest, compared to the extent of their depressed calcium absorption. Therapy with 1,25-(OH)2D3 for 1 wk restored phosphate absorption rate to near normal. With or without 1,25-(OH)2D3 therapy, phosphate absorption was not influenced by calcium in the perfused test solutions. Examination of kinetic data suggests that the vitamin D deficiency of chronic renal failure causes a reduction by half in the rate of active phosphate absorption. By contrast, our data suggest that vitamin D deficiency does not alter passive phosphate absorption. By aspirating jejunal contents after ingestion of different foods, with and without aluminum hydroxide, the physiologic luminal phosphate concentration was found to vary between 0.7 and 12.2 mM. At the lower end of this range, phosphate absorption would be mediated entirely by active transport; at the higher phosphate concentrations, phosphate absorption would be mainly mediated by passive transport.
Adult↗
Imaging of the gallbladder.
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Cholangiography↗
Pathogenesis of fecal incontinence in diabetes mellitus: evidence for internal-anal-sphincter dysfunction.
We studied 16 patients with diabetes and fecal incontinence. The onset of incontinence coincided with the onset of chronic diarrhea in most patients. Episodes of incontinence occurred when stools were frequent and loose; however, 24-hour stool weights were usually within normal limits. All patients had evidence of autonomic neuropathy, and one third had steatorrhea. Incontinent diabetics had a lower mean basal anal-sphincter pressure than 35 normal subjects (63 +/- 4 vs. 37 +/- 4 mm Hg; P less than 0.001), reflecting abnormal internal-anal-sphincter function. The increment in sphincter pressure with voluntary contraction (external-sphincter function) was not significantly different from normal. Incontinent diabetics also had impaired continence for a solid sphere and for rectally infused saline. In contrast, 14 diabetics without diarrhea or incontinence had normal sphincter pressures and normal results on tests of continence, even though 79 per cent had evidence of autonomic neuropathy and nearly half had steatorrhea. We conclude that incontinence in diabetic patients is related to abnormal internal-anal-sphincter function, and that as a group, diabetics without diarrhea do not have latent defects in continence.
Adult↗