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Biomedical subjects

C A Santa Ana

Publications and source records attributed to C A Santa Ana.

At least 37 records · Page 2Linked to original sources

Comparison of endogenous and radiolabeled bile acid excretion in patients with idiopathic chronic diarrhea.

Fecal recovery of radioactivity after ingestion of a bolus of radiolabeled bile acid is abnormally high in most patients with idiopathic chronic diarrhea. To evaluate the significance of this malabsorption, concurrent fecal excretion of both exogenous radiolabeled bile acid and endogenous (unlabeled) bile acid were measured in patients with idiopathic chronic diarrhea. Subjects received a 2.5-microCi oral dose of taurocholic acid labeled with 14C in the 24th position of the steroid moiety. Endogenous bile acid excretion was measured by a hydroxysteroid dehydrogenase assay on a concurrent 72-h stool collection. Both radiolabeled and endogenous bile acid excretion were abnormally high in most patients with chronic diarrhea compared with normal subjects, even when equivoluminous diarrhea was induced in normal subjects by ingestion of osmotically active solutions. The correlation between radiolabeled and endogenous bile acid excretion was good. However, neither radiolabeled nor endogenous bile acid excretion was as abnormal as is typically seen in patients with ileal resection, and none of these diarrhea patients responded to treatment with cholestyramine with stool weights less than 200 g. These results suggest (a) that this radiolabeled bile acid excretion test accurately reflects excess endogenous bile acid excretion; (b) that excess endogenous bile acid excretion is not caused by diarrhea per se; (c) that spontaneously occurring idiopathic chronic diarrhea is often associated with increased endogenous bile acid excretion; and (d) that bile acid malabsorption is not likely to be the primary cause of diarrhea in most of these patients.

Adult↗

A low-sodium solution for gastrointestinal lavage.

Golytely is a sodium sulfate-based solution used for lavage cleansing of the colon. Although most patients and physicians prefer Golytely lavage over other methods of bowel cleansing, its highly salty taste is a drawback. This report describes the development of a modified lavage solution that has a barely perceptible salty taste. This solution was developed by removing sodium sulfate, increasing the concentration of polyethylene glycol, and making minor adjustments in the concentration of other salts. Golytely, reduced sodium sulfate Golytely (Golytely-RSS), and a balanced electrolyte solution were infused into the stomachs of normal subjects. After steady-state lavage conditions were established, the rates of fluid and electrolyte absorption were measured. Average fluid absorption rate was 791 ml/h with the balanced electrolyte solution, compared with only 63 and 45 ml/h with Golytely and Golytely-RSS, respectively. Golytely-RSS was studied at 3 infusion rates, from 0.9-1.8 L/h, and the time and volume of solution required for colon cleansing was determined; the lower infusion rate (0.9 L/h) took longer but required less solution to cleanse the colon. In conclusion, Golytely-RSS has the essential feature of Golytely; i.e., lavage is associated with negligible salt and water absorption. The less-salty taste of Golytely-RSS may make it less difficult to drink and thereby enhance patient compliance; the total volume of solution required for cleansing is less when the solution is ingested at 0.9 L/h than when the ingestion rate is 1.8 L/h.

Colon↗

Carbohydrate malabsorption. Its measurement and its contribution to diarrhea.

The major purpose of this research was to gain insight into the effect of carbohydrate malabsorption on fecal water output. To do this we measured daily fecal output of total carbohydrate, reducing sugars, and organic acids (a product of bacterial fermentation). Normal subjects were studied in their native state and when diarrhea was induced by mechanisms that did and did not involve carbohydrate malabsorption. Patients with malabsorption syndrome were also studied. We concluded that: (a) Excretion of carbohydrate and its breakdown products can be expressed as a single number by converting organic acids to their monosaccharide equivalents. (b) Diarrhea per se causes only a trivial increase in fecal carbohydrate excretion. (c) The molar output of osmotic moieties in feces due to unabsorbed carbohydrate can be determined by adding fecal reducing sugars to organic acids and their obligated cations. This expression parallels almost exactly the effect of increasing doses of lactulose (a nonabsorbable sugar) on fecal water output; one excreted millimole obligates 3.5 g of stool water. This relationship can be used to predict the effect of carbohydrate malabsorption on stool water output in patients with diarrhea. (d) 12 of 19 patients with malabsorption syndrome due to various diseases had excessive fecal excretion of carbohydrate and its breakdown products; of the diseases that cause malabsorption syndrome, combined small and large bowel resection is most likely to result in excessive fecal excretion of carbohydrate and monosaccharide equivalents. In 6 of these 19 patients carbohydrate malabsorption appeared to be the major cause of diarrhea.

Carbohydrate Metabolism↗

Effect of the time of administration of calcium acetate on phosphorus binding.

Phosphorus binders are given to patients with renal failure to increase gastrointestinal excretion of phosphorus. To determine the relative importance of the binding of dietary as compared with endogenous phosphorus and to determine the optimal dose schedule, we gave either 4.4 g of calcium acetate (25 mmol of calcium) or a placebo to six normal subjects on each of seven different schedules in a randomized sequence. The net gastrointestinal balance of phosphorus and calcium was determined by a one-day lavage technique. After a meal containing approximately 12 mmol of phosphorus, the mean phosphorus absorption (+/- SE) measured 9.17 +/- 0.36 mmol (78 percent) with placebo but decreased to 3.81 +/- 0.58 mmol (31 percent) when calcium acetate was given immediately before the meal (representing binding of 5.36 +/- 0.77 mmol of phosphorus). Similar binding was observed when calcium acetate was given immediately after the meal and when half the dose was given before and half after the meal. In contrast, when calcium acetate was given two hours after the meal or while the subject was fasting, phosphorus binding was reduced to 2.00 +/- 0.52 mmol and 1.81 +/- 0.84 mmol, respectively. Calcium absorption from calcium acetate averaged 21 +/- 1 percent when the binder was given with a meal; absorption from calcium acetate averaged 40 +/- 4 percent when the binder was given while the subject was fasting. We conclude that calcium acetate increases fecal excretion of phosphorus by binding both dietary and endogenous phosphorus, but the binding of dietary phosphorus is quantitatively much more important. For the most efficient phosphorus binding, calcium (and presumably other phosphorus-binding cations) should be given with meals.

Acetates↗

Loss of absorptive capacity for sodium chloride as a cause of diarrhea following partial ileal and right colon resection.

Previous studies have emphasized the role of bile acid and fat malabsorption as the cause of the diarrhea that may follow ileal and right colon resection; unabsorbed bile acids and fat are believed to reduce sodium chloride and water absorption in the remaining colon. In this paper we report studies in eight patients with severe postresection diarrhea, in search of a more basic defect in sodium chloride absorption, ie, a loss of sodium chloride absorptive capacity as a direct consequence of resection of sodium chloride absorption sites. First, we determined whether or not diarrhea persisted during a 48-hr fast; in all patients diarrhea and large fecal electrolyte losses continued during a fast. Second, we measured sodium chloride and water absorption rates during total gut perfusion with a balanced electrolyte solution; compared to normal controls, the patients absorbed 23-31% less water, sodium, and chloride. In three patients who could be studied further, the absorptive defect was markedly accentuated when the perfusing solution was such that sodium chloride absorption had to take place against a concentration gradient. These observations indicate that postresection diarrhea patients have a reduced capacity to absorb sodium chloride, particularly when there is a concentration gradient between lumen and plasma. Although all of these patients had malabsorption of radiolabeled taurocholic acid, there was only a modest and statistically insignificant reduction in daily stool weight during treatment with large doses of cholestyramine, suggesting that bile acid malabsorption was not responsible for a major part of their diarrhea.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Calcium acetate, an effective phosphorus binder in patients with renal failure.

Calcium salts are increasingly used as phosphorus binders in patients with chronic renal failure. Calcium carbonate is the principal salt presently utilized, however, other calcium salts may be more effective and safer phosphorus binders. Theoretical calculations, in vitro experiments, and in vivo studies in normal subjects have shown calcium acetate to be a more effective phosphorus binder than other calcium salts. This salt has not previously been studied in patients with chronic renal failure. We used a one-meal gastrointestinal balance technique to measure phosphorus absorption, calcium absorption and phosphorus binding in six patients with chronic renal failure. Calcium acetate was compared with calcium carbonate and placebo. Equivalent doses (50 mEq Ca++) of calcium acetate bound more than twice as much phosphorus (106 +/- 23 mg) as calcium carbonate (43 +/- 39 mg) P less than 0.05. When phosphorus binding was factored for calcium absorption, calcium acetate bound 0.44 mEq HPO4 =/mEq absorbed Ca++ compared with 0.16 mEq HPO4 = bound/mEq Ca++ absorbed with calcium carbonate. More efficient phosphorus binding permits serum phosphorus concentration to be controlled with lower doses of calcium salts. The higher phosphorus binding/calcium absorption ratio coupled with a lower dose indicates that less calcium will be absorbed when calcium acetate is used for phosphorus control. Markedly positive calcium balance, hypercalcemia and ectopic calcification should be less likely to occur with this drug than other calcium salts.

Acetates↗

Reduction of dietary phosphorus absorption by phosphorus binders. A theoretical, in vitro, and in vivo study.

Antacids used to decrease phosphorus absorption in patients with renal failure may be toxic. To find more efficient or less toxic binders, a three-part study was conducted. First, theoretical calculations showed that phosphorus binding occurs in the following order of avidity: Al3+ greater than H+ greater than Ca2+ greater than Mg2+. In the presence of acid (as in the stomach), aluminum can therefore bind phosphorus better than calcium or magnesium. Second, in vitro studies showed that the time required to reach equilibrium varied from 10 min to 3 wk among different compounds, depending upon solubility in acid and neutral solutions. Third, the relative order of effectiveness of binders in vivo was accurately predicted from theoretical and in vitro results; specifically, calcium acetate and aluminum carbonate gel were superior to calcium carbonate or calcium citrate in inhibiting dietary phosphorus absorption in normal subjects. We concluded that: (a) inhibition of phosphorus absorption by binders involves a complex interplay between chemical reactions and ion transport processes in the stomach and small intestine; (b) theoretical and in vitro studies can identify potentially better in vivo phosphorus binders; and (c) calcium acetate, not previously used for medical purposes, is approximately as efficient as aluminum carbonate gel and more efficient as a phosphorus binder than other currently used calcium salts.

Acetates↗

Studies of osmotic diarrhea induced in normal subjects by ingestion of polyethylene glycol and lactulose.

The purpose of these studies was to gain insight into the pathophysiology of pure osmotic diarrhea and the osmotic diarrhea caused by carbohydrate malabsorption. Diarrhea was induced in normal volunteers by ingestion of polyethylene glycol (PEG), which is nonabsorbable, not metabolized by colonic bacteria, and carries no electrical charge. In PEG-induced diarrhea, (a) stool weight was directly correlated with the total mass of PEG ingested; (b) PEG contributed 40-60% of the osmolality of the fecal fluid, the remainder being contributed by other solutes either of dietary, endogenous, or bacterial origin; and (c) fecal sodium, potassium, and chloride were avidly conserved by the intestine, in spite of stool water losses exceeding 1,200 g/d. Diarrhea was also induced in normal subjects by ingestion of lactulose, a disaccharide that is not absorbed by the small intestine but is metabolized by colonic bacteria. In lactulose-induced diarrhea, (a) a maximum of approximate 80 g/d of lactulose was metabolized by colonic bacteria to noncarbohydrate moieties such as organic acids; (b) the organic acids were partially absorbed in the colon; (c) unabsorbed organic acids obligated the accumulation of inorganic cations (Na greater than Ca greater than K greater than Mg) in the diarrheal fluid; (d) diarrhea associated with low doses of lactulose was mainly due to unabsorbed organic acids and associated cations, whereas with larger doses of lactulose unmetabolized carbohydrates also played a major role; and (e) the net effect of bacterial metabolism of lactulose and partial absorption of organic acids on stool water output was done dependent. With low or moderate doses of lactulose, stool water losses were reduced by as much as 600 g/d (compared with equimolar osmotic loads of PEG); with large dose, the increment in osmotically active solutes within the lumen exceeded the increment of the ingested osmotic load, and the severity of diarrhea was augmented.

Adult↗

Effect of amiloride on sodium transport in the proximal, distal, and entire human colon in vivo.

In vitro studies under short-circuited conditions suggest that amiloride, a diuretic agent which is thought to block apical membrane sodium entry, has significant effects on sodium absorption by the human colon. To evaluate this in vivo, we studied the effect of amiloride applied in concentrations of 10(-5) and 10(-4) M on sodium transport and potential difference (PD) in human colon during steady-state perfusion. Net sodium absorption was reduced 25% by amiloride and chloride absorption by 15%; potassium and bicarbonate secretion rates were enhanced. In other studies the colon was divided into a proximal and distal test segment by endoscopic introduction of a collection channel to the descending colon-sigmoid junction. Comparison of tritiated water absorption by the two segments indicated that the distal segment comprised approximately 20% of the total colon surface area. However, the distal test segment only accounted for 5-7% of total sodium, chloride, or water absorption; in contrast, 17-20% of total potassium or bicarbonate secretion occurred there. In the proximal test segment, amiloride reduced net sodium absorption by almost one third from 21.0 to 14.4 mmol/hr (P less than 0.02) but had no significant effect on PD. In the distal test segment, amiloride produced a 25% reduction in mean sodium absorption from 1.2 to 0.9 mmol/hr, but this reduction was not statistically significant; however, potential difference was significantly reduced by 33% (P less than 0.02). These results suggest that most sodium absorption in normal human colon in vivo is mediated by transport processes which are insensitive to these doses of amiloride.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Osmotic effects of polyethylene glycol.

Polyethylene glycol (PEG) has been used to increase the osmotic pressure of fluids used to cleanse the gastrointestinal tract. However, little is known about its osmotic activity. To investigate this activity systematically, solutions of PEG of differing molecular weights were made and subjected to measurement of osmolality by both freezing point depression and vapor pressure osmometry. Measured osmolality was increasingly greater than predicted from average molecular weight as PEG concentration increased. Measurement of sodium activity in NaCl/PEG solutions by means of an ion-selective electrode suggested that the higher than expected osmolality could be due in part to interactions that, in effect, sequestered water from the solution. Osmolality was consistently greater by freezing point osmometry than by vapor pressure osmometry. To determine which osmometry method reflected biologically relevant osmolality, normal subjects underwent steady-state total gut perfusion with an electrolyte solution containing 105 g/L of PEG 3350. This produced rectal effluent that was hypertonic by freezing point osmometry but isotonic by vapor pressure osmometry. Assuming that luminal fluid reaches osmotic equilibrium with plasma during total gut perfusion, this result suggests that the vapor pressure osmometer accurately reflects the biologically relevant osmolality of intestinal contents. We conclude that PEG exerts more of an osmotic effect than would be predicted from its molecular weight. This phenomenon may reflect interactions between PEG and water molecules that alter the physical chemistry of the solution and sequester water from the solution.

Freezing↗

Calcium absorption: effect of meal and glucose polymer.

Various nonelectrolyte meal components such as glucose and lysine enhance gastrointestinal calcium absorption under experimental conditions. The effect of a mixed meal on Ca absorption from Ca supplements is unknown. The effect of glucose polymer on Ca absorption when ingested with food also is unknown. Using a single-day method, we measured net Ca absorption from Ca carbonate when ingested in fasting state, with a steak and potatoes meal, and with the meal and 50 g glucose polymer. Eight healthy human subjects were studied after a 500-mg elemental Ca dose. Mean net Ca absorption was 195 +/- 18 mg (4.87 +/- 0.45 mmol) fasting, 213 +/- 21 mg (5.31 +/- 0.52 mmol) with a meal, and 179 +/- 16 mg (4.47 +/- 0.40 mmol) with a meal plus glucose polymer. The differences are not statistically significant. In normal people Ca absorption from Ca carbonate was not significantly enhanced by a meal or by 50 g glucose polymer ingested with food.

Adult↗

Gastrointestinal absorption of calcium from milk and calcium salts.

Whether ingested calcium is absorbed more efficiently from freely water-soluble calcium salts than from poorly soluble salts is unclear. It is also unknown whether calcium is absorbed better from dairy products than from calcium salts. Using a method by which the net absorption of calcium can be accurately measured after a single dose, we studied eight healthy fasting subjects after they took a 500-mg dose of calcium from each of five calcium salts with various degrees of water solubility and from milk. The order of administration of the agents given was randomly determined. The mean (+/- SEM) net calcium absorption, in decreasing order of the solubility of the salts, was 32 +/- 4 percent from calcium acetate, 32 +/- 4 percent from calcium lactate, 27 +/- 3 percent from calcium gluconate, 30 +/- 3 percent from calcium citrate, and 39 +/- 3 percent from calcium carbonate. The differences in absorption were not statistically significant according to analysis of variance. On the basis of in vitro solubility experiments in acid mediums, we hypothesize that acid dissolution in the gastrointestinal tract may be responsible for the similar absorption of calcium from salts with widely different water solubilities. Calcium absorption from whole milk (31 +/- 3 percent) was similar to absorption from calcium salts. We conclude that calcium absorption from carbonate, acetate, lactate, gluconate, and citrate salts of calcium, and from whole milk, is similar in fasting healthy young subjects. Further study will be required to determine whether the results would be different in older subjects, with a higher dose of calcium, or if the calcium was ingested with food.

Acetates↗

Studies of the prevalence and significance of radiolabeled bile acid malabsorption in a group of patients with idiopathic chronic diarrhea.

We studied radiolabeled fecal bile acid excretion in 11 normal subjects and 17 patients with idiopathic chronic diarrhea for three major purposes: to establish normal values for this test in the presence of increased stool volumes (induced in normal subjects by ingestion of poorly absorbable solutions); to test for bile acid malabsorption in the patients and to correlate this with an independent test of ileal function, the Schilling test; and to compare the results of the bile acid excretion test with the subsequent effect of a bile acid binding agent (cholestyramine) on stool weight. In normal subjects fecal excretion of the radiolabel was increased with increasing stool volumes. As a group, patients with idiopathic chronic diarrhea excreted radiolabeled bile acid more rapidly than normal subjects with induced diarrhea (t1/2 56 +/- 8 vs. 236 +/- 60 h, respectively, p less than 0.005). There was a statistically significant positive correlation between t1/2 of radiolabeled bile acid and Schilling test results in these patients. Although 14 of 17 patients absorbed labeled taurocholic acid less well than any of the normal subjects with comparable volumes of induced diarrhea, cholestyramine had no statistically significant effect on stool weight in the patient group, and in none of the patients was stool weight reduced to within the normal range. In summary, most patients with idiopathic chronic diarrhea have bile acid malabsorption (as measured by fecal excretion of labeled bile acid), but they do not respond to cholestyramine therapy with a significant reduction in stool weight. Although the significance of these findings was not clearly established, the most likely interpretation is that bile acid malabsorption is a manifestation of an underlying intestinal motility or absorptive defect rather than the primary cause of diarrhea.

Adult↗

Urinary excretion of polyethylene glycol 3350 and sulfate after gut lavage with a polyethylene glycol electrolyte lavage solution.

Ingestion of an electrolyte lavage solution containing polyethylene glycol 3350 and sulfate is an effective method of cleansing the colon for diagnostic studies. Polyethylene glycol and sulfate are considered poorly absorbed from the gastrointestinal tract. Because of the quantities administered, concern exists about potential toxicity of absorption of even a small percentage, particularly for polyethylene glycol. We measured the urinary excretion of both polyethylene glycol and sulfate in normal subjects and inflammatory bowel patients. Absorption of polyethylene glycol can be assessed by measuring recovery in urine, as 85%-96% of an intravenous load is excreted in urine. Similarly, appreciable sulfate absorption would exceed renal tubular reabsorption and result in increased urinary excretion. Mean percent polyethylene glycol load recovered in urine was minimal and similar for normal (0.06%) and inflammatory bowel (0.09%) subjects. Urinary sulfate excretion after lavage was also similar for both groups and was not different from baseline. These results do not suggest the likelihood of toxicity due to polyethylene glycol 3350 or sulfate absorption during gut lavage with this solution.

Colitis, Ulcerative↗

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↗

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↗