Active and passive bile acid absorption in man. Perfusion studies of the ileum and jejunum.

Absorption of the major human bile acids was studied in 12 healthy volunteers by steady state perfusion of the ileum in 112 experiments and of the jejunum in 48 experiments. Use of a randomized order of four perfusions on 1 day of study and use of up to 4 consecutive days of study in a subject allowed important comparisons of data from the same individuals. That there is active ileal absorption of chenodeoxycholic, glycochenodeoxycholic, and taurocholic acids in man was supported by the finding of saturation kinetics and of competition for absorption among conjugated bile acids. Values for apparent kinetic constants (apparent maximal transport velocity [(*)V(max)] and apparent Michaelis constant) in man are similar to those in other species. The ileum absorbed chenodeoxycholic acid more rapidly than its glycine conjugate, due mainly to a ninefold greater permeability for the free acid. Taurocholate had the highest (*)V(max) and was absorbed more rapidly than glycochenodeoxycholate. Passive permeability of the jejunum to bile acids was twice that of the ileum, and the permeabilities to free and glycine-conjugated chenodeoxycholate were in the same ratio as in the ileum (9: 1). Jejunal permeability to chenodeoxycholic acid was three times that to cholic acid. Variation of intraluminal pH by up to 1.4 units did not influence jejunal uptake of free bile acids. These results, which are comparable with those from animal experiments, provide a basis for estimation of intestinal reabsorption of bile acids in intact man.

Inhibition of ileal water absorption by intraluminal fatty acids. Influence of chain length, hydroxylation, and conjugation of fatty acids.

The influence of fatty acids on ileal absorption of water, electrolytes, glucose, and taurocholate was examined in Thirty-Vella fistulas in five mongrel dogs. Fatty acid absorption also was measured. Segments of terminal ileum were perfused at steady state with isotonic electrolyte solutions containing 11.2 mM glucose, 4.5 mM taurocholate, and 0.1-5.0 mM fatty acid. Three C(18) fatty acids, oleic acid, 10(9)-hydroxystearic acid, and ricinoleic acid, completely inhibited water absorption at 5 mM. Sodium, chloride, and potassium absorptions were inhibited in parallel with absorption of water. Differences between the potencies of C(18) fatty acids were apparent when lesser concentrations were perfused. Dodecanoic and decanoic acids were as effective as C(18) fatty acids at 5 mM but octanoic and hexanoic acids were ineffective. The polar group of C(18) fatty acids was modified by conjugating oleic and ricinoleic acids with taurine. When these compounds and a substituted C(18) fatty acid, p-n-decylbenzenesulfonate, were perfused, water absorption was also inhibited. Short-chain fatty acids (C(3) and C(4)) and their hydroxylated derivatives were ineffective at 5 mM. When water absorption was inhibited, absorption of glucose and taurocholate was decreased. We speculate that the phenomenon of inhibition of water and electrolyte absorption by fatty acids may be relevant to steatorrhea and diarrhea in man.

Colonic secretion of water and electrolytes induced by bile acids: perfusion studies in man.

Each of the three major bile acids of man was tested for its influence on electrolyte and water absorption in the human colon. Transport from isotonic solutions, with or without added bile acids, was compared in 35 studies on 20 healthy volunteers by colonic perfusions under steady-state conditions. Electrolytes and water were always absorbed from control solutions, but dihydroxy bile acid solutions induced continuous secretion or inhibition of sodium, potassium, and water absorption, which was reversible. Deoxycholic acid caused consistent secretion at 3 mm concentrations, whereas chenodeoxycholic acid did not induce secretion until the concentration was 5 mm. The trihydroxy bile acid (cholic acid) produced no significant change in absorption at 10 mm. Inhibition of absorption was also induced by mixtures of the glycine or taurine conjugated bile acids. Secretion of sodium and chloride, induced by bile acid perfusion, was linearly correlated with secretion of water; potassium secretion was relatively constant regardless of the volume of secretion. These results establish a striking influence of bile acids on colonic absorptive activity, provide an explanation in part for the diarrhea that frequently accompanies ileal disease or resection, and imply that diarrhea should occur in other disease states that produce elevated concentrations of dihydroxy bile acids in the colonic lumen.

Effects of oleic and ricinoleic acids on net jejunal water and electrolyte movement. Perfusion studies in man.

To examine the effects of oleic acid and ricinoleic acid on jejunal absorption, steady-state jejunal perfusions were performed in healthy volunteers. Taurocholate, used to solubilize the fatty acids, did not influence absorption. Both fatty acids (concentration, 10 mM) reversed electrolyte and water net movement; that is, they induced fluid secretion; this effect was rapidly reversible. Ricinoleic acid (the active principle of castor oil) was the more potent, producing fluid secretion when perfused at concentrations at which oleic acid was without effect. However, ricinoleic acid was absorbed more slowly than was oleic acid, and hence was associated with higher intraluminal concentrations. Addition of lecithin and monoolein did not diminish the secretory effect of ricinoleic acid; addition of a secretory bile acid (taurodeoxycholate) did not enhance the effect. The response of the jejunal mucosa to a known cathartic provides observations pertinent to the pathophysiology of steatorrheal diseases in man. Dietary fatty acid also has secretory properties with respect to the human intestine; bacterial hydration, to hydroxy fatty acids, is not required to induce fluid secretion.

Effect of glycine-conjugated bile acids with and without lecithin on water and glucose absorption in perfused human jejunum.

Perfusion studies were performed in healthy volunteers to test whether the secretory effect of conjugated bile acids, previously shown for the colon, was also present in the jejunum. A perfusion system with a proximal occlusive balloon (and continuous aspiration of duodenal secretions) was used; isotonic test solutions contained glycine-conjugated bile acids with or without lecithin. Fluid movement was measured by changes in the concentration of polyethylene glycol (PEG, mol wt 4,000). Conjugated dihydroxy bile acids inhibited electrolyte and fluid absorption and, at higher concentrations, evoked secretion of an isotonic fluid. Glucose absorption continued, despite fluid secretion, but its rate decreased. The secretory effects of bile acids were abolished by the addition of lecithin to the bile acid solutions. A trihydroxy bile acid (cholylglycine) had no effect on jejunal absorption. Small amounts (6-9%) of conjugated bile acids were absorbed in the jejunum; lecithin was well absorbed (72-90%). The results indicate that dihydroxy bile acids influence salt and water transport in the human jejunum but that this effect may be abolished when a polar lipid such as lecithin is present. We speculate that this effect of bile acids may modify fluid movement in the small intestine postprandially after fat absorption has occurred.

Components of fiber bind iron in vitro.

Interactions among fiber, inorganic iron, and substances known to chelate iron were examined in vitro. Cellulose, neutral and acid fractions of lignin, psyllium mucilage, and pectin were incubated with 59Fe SO4 at various pH's, in various concentrations, and in the presence or absence of known chelators of iron including ascorbate, citrate, cysteine, fructose, and EDTA. Insoluble components of fiber were tested in a precipitation-centrifugation system, soluble components were tested by equilibrium dialysis. Lignins and psyllium mucilage had the greatest capacity to bind ferrous iron under conditions that approximated those of the proximal intestine postprandially; cellulose and pectin were less potent. Dissociation constants of binding were similar for several components, suggesting the existence of comparable binding sites in different components of fiber. Citrate and EDTA inhibited the binding of iron markedly but other chelators were much less effective. These reactions among fiber, inorganic iron, and other constituents of food may influence the bioavailability of dietary iron and the simple systems described here offer a means of dissecting interactions that are complex in vivo.

Components of fiber impair iron absorption in the dog.

We have demonstrated previously that semipurified components of fiber bind ferrous iron in vitro. The present studies examined the possibility that these same fibers would decrease absorption of iron by the canine small bowel. Healthy and anemic dogs were studied chronically. Two preparations were needed; soluble components of fiber were tested by continuous perfusion of a duodenojejunal segment of approximately 100 cm, insoluble components were tested in Thiry-Vella fistulae of jejunum (25 cm). The results confirm that, 1) anemic dogs absorb iron more efficiently than do healthy animals, and 2) that there is a slight, but significant, decrease in iron absorption during the 4 to 6 h of an acute experiment. To obviate problems of interpretation because of the latter point, all studies featured a control period, before and after, the test period. Lignin and psyllium mucilage were potent inhibitors of iron absorption, pectin less so, and cellulose was without effect in this system. The results in vivo correlate well with the binding of iron in vitro.

Recovery of dietary iron and zinc from the proximal intestine of healthy man: studies of different meals and supplements.

The technique of marker perfusion of the upper gastrointestinal tract was used to measure intraluminal quantities of iron and zinc after test meals in healthy humans. Two different meals, one based on hamburger (with a predominance of heme iron, 7.5 mg/meal) and one based on cereal (containing inorganic iron; 1.4, 5.3, or 4.6 mg), were used. In addition, the luminal behavior of ferrous sulfate and hydrogen-reduced metallic iron (used as supplements to the cereal meal) were compared. Different meals also contained low (2.4 mg) or high (5.5 mg) amounts of zinc. The intubation techique allowed disappearance of metals from the duodenum and jejunum to be compared. The patterns of luminal flow were different for iron and zinc. Whereas iron was never recovered from the lumen at levels above those ingested in meals, zinc was recovered from the duodenum at levels greater than those ingested. These findings suggest that zinc, but little iron, is added to chyme in the upper gut during digesting and absorption. Bioavailability of different forms of iron, as judged by their luminal disappearance, were similar. Inorganic iron, ferrous sulfate, and hydrogen-reduced metallic iron were absorbed about as effectively as was heme iron. Iron disappeared preferentially from the duodenum but the site of zinc absorption appeared to be more distal.

Evaluation of an inexpensive screening scintigraphic test of gastric emptying.

UNLABELLED: Our goal was to study the accuracy of a limited assessment relative to the traditional and obtain a more detailed approach to measure gastric emptying. METHODS: We prospectively evaluated 35 patients referred to our laboratory with suspected fast or slow gastric emptying. Transit was measured radioscintigraphically after ingestion of an egg meal containing 99mTc-Amberlite pellets. Gastric emptying was analyzed by power exponential analysis. Diagnostic accuracy of simpler indices (gastric residual at 2 and 4 hr) was determined by comparing the categorization of patients as normal or abnormal relative to previously published normal data from our laboratory. RESULTS: Gastric residual at 2 hr showed greater diagnostic accuracy for accelerated gastric emptying with 90% sensitivity at 90% specificity. Gastric residual at 4 hr was less accurate for accelerated emptying, but was more accurate at detecting delayed gastric emptying with 100% sensitivity at 70% specificity. In contrast, sensitivity and specificity of gastric residual at 2 hr for slow emptying were low (100% sensitivity with 20% specificity) emphasizing the importance of obtaining a scan later than 2 hr for detecting delayed gastric emptying. CONCLUSION: Selective scans taken at 2 and 4 hr provide an excellent screening test for detecting fast or slow gastric emptying; the accuracy of 2-hr data is optimal for accelerated emptying and that of the 4-hr data greater for delayed emptying. This strategy provides a simple, less expensive way to evaluate gastric emptying in clinical practice with acceptable sensitivity and specificity as an initial test for patients with clinically suspected gastric stasis or dumping syndromes.

Ricinoleic acid (castor oil) alters intestinal surface structure. A scanning electronmiscroscopic study.

To determine if sodium ricinoleate, the active principle of castor oil, alters mucosal surface structure of the small intestine, rabbit ileum was perfused with isotonic buffer or buffer containing 10 mM of sodium ricinoleate. Mucosal biopsies were examined by scanning electron microscopy. Sodium ricinoleate produced deep clefts or holes at the tips of villi, and at the bases of these clefts unusual cells could be resolved. The microvillus surface of the intestine was also altered at the tips and sides of villi. Microvilli were clumped into "tufts" with numerous intervening "cracks" appearing on the surface. These changes may relate to the well-documented capacity of ricinoleate and dietary long-chain fatty acids to evoke fluid secretion in the intestine. The findings thus pertain to the pharmacology of castor oil and the pathophysiology of steatorrheal disease.

Chronic pouchitis after ileal pouch-anal anastomosis: responses to butyrate and glutamine suppositories in a pilot study.

Nonspecific, idiopathic inflammation of ileal pouch mucosa ("pouchitis") after ileal pouch-anal anastomosis is a common complication of this surgical approach. The epithelium of the pouch is ileal, but variable degrees of colonic metaplasia are natural sequelae of construction of such a pouch. One hypothesis is that pouchitis is caused by a deficiency of epithelial nutrition. Thus, a lack of butyric acid (the principal metabolic fuel of colonocytes) or of glutamine (the main fuel of enterocytes) may develop. In this study, our aims were to determine the concentration of total short-chain fatty acids in random stool samples obtained from patients with an ileal pouch-anal anastomosis with and without pouchitis and to test the therapeutic effects of butyrate and glutamine suppositories on pouchitis. During the study, all conventional therapy for pouchitis was discontinued. For 21 days, 9 patients participated in a butyrate trial, and 10 patients were treated with glutamine. Total concentrations of fecal short-chain fatty acids were significantly less in patients with pouchitis than in those without pouchitis. During treatment, 6 of the 10 patients who received glutamine had no recurrence of symptoms, but only 3 of the 9 patients who received butyrate responded similarly. Hence, further studies of glutamine in the treatment of pouchitis seem warranted.

Constipation and fecal incontinence in the elderly population.

OBJECTIVE: To describe the assessment and management of constipation and fecal incontinence in elderly patients. DESIGN: We reviewed pertinent publications in the recent medical literature and outlined effective management strategies for constipation and fecal incontinence in the geriatric population. RESULTS: Constipation can be classified into two syndromes--functional constipation and rectosigmoid outlet delay. Evaluation consists of elicitation of a detailed history, directed physical examination, and selected laboratory tests. Management involves nonpharmacologic (such as exercise and fiber) and pharmacologic measures. Fecal incontinence in elderly patients can be due to stool impaction, medications, dementia, or neuromuscular dysfunction. Management options include modification of contributing disorders, pharmacologic therapy, and behavioral techniques. CONCLUSION: Constipation and fecal incontinence are common and often debilitating conditions in elderly patients. Management should be highly individualized and dependent on cause, coexisting morbidities, and cognitive status.

Rapid gastric emptying in patients with functional diarrhea.

OBJECTIVE: To analyze our experience in patients with chronic diarrhea by using a noninvasive transit study that measures gastric emptying as well as small bowel and colonic transit. MATERIAL AND METHODS: Results from 94 consecutive transit tests, for which diarrhea was the main indication, were reviewed and correlated with the final classification of patients as having an organic or nonorganic disorder. RESULTS: Sixty patients were considered to have a nonorganic cause of diarrhea, of whom 15 had previously undergone cholecystectomy. The other 34 patients were considered to have diarrhea on the basis of an organic diagnosis. Gastric emptying was more often rapid in patients with a nonorganic cause (P < 0.05), but not if cholecystectomy had been performed previously. Small bowel transit was fast more often in patients with organic diarrhea than in those with no organic cause of the diarrhea (P < 0.05); colonic transits showed no significant differences among groups. CONCLUSION: The findings implicate a motor abnormality of the upper gut, rapid gastric emptying, as a pathophysiologic mechanism of functional bowel disorders with diarrhea. The results imply that additional prospective observations should be worth-while.

Assessment of Campylobacter-like organisms in the postoperative stomach, iatrogenic gastritis, and chronic gastroduodenal diseases: preliminary observations.

Campylobacter-like organisms (provisionally named C. pyloridis) were demonstrated in gastric biopsy specimens by histopathologic analysis and bacterial culture. C. pyloridis organisms were found in 12 of 26 patients (46%) with gastric or duodenal ulcer but in none of 10 healthy volunteers without histologic evidence of gastritis. Iatrogenic antral gastritis, induced by 7 days of treatment with nonsteroidal anti-inflammatory drugs, was not associated with the presence of C. pyloridis. Organisms were found in 6 of 24 patients who had undergone gastric operations, but the prevalence of C. pyloridis was not higher in those with symptoms of alkaline reflux gastritis than in asymptomatic postgastrectomy control patients. We conclude that C. pyloridis is less common in patients with drug-induced and postoperative gastritis than in patients with peptic ulcer.

Ricinoleic acid effects on rabbit intestine: an ultrastructural study.

In fasting rabbits, segments of ileum and colon were perfused with ricinoleic acid. This fatty acid is the active principle of castor oil and stimulates intestinal fluid secretion. Biopsies taken from perfused segments were examined by electron microscopy after staining with lanthanum hydroxide and ruthenium red. These stains, which typically bind to extracellular surfaces, were used to assess the integrity of junctional zones between cells. In this study, ricinoleate did not alter ruthenium or lanthanum staining in junctional areas, a finding suggesting that ricinoleate does not cause fluid secretion by selectively disrupting these areas.

Does Helicobacter pylori colonize the gastric mucosa of Meckel's diverticulum?

Helicobacter pylori (formerly, Campylobacter pylori) is a highly adapted organism that seems to infect only gastric-type mucosa. In this study, we attempted to determine whether gastric epithelium at a site distant from the stomach, the heterotopic gastric mucosa of Meckel's diverticulum, was susceptible to colonization by H. pylori. Retrospectively, we examined biopsy specimens from 23 patients who had undergone resection of Meckel's diverticulum that contained heterotopic gastric mucosa. As a methodologic control, we also reviewed antral biopsy specimens from 18 patients with chronic duodenal ulcer who had undergone antrectomy. Heterotopic gastric mucosa in Meckel's diverticulum was of antral type in 13 patients and fundic type in 10 patients. Six patients had an ulcer in the diverticulum. No evidence of chronic or active chronic gastritis was detected in the heterotopic gastric mucosa. H. pylori was not found in any Meckel's diverticula but was present in the antrum of 89% of patients with duodenal ulcer. These results suggest that H. pylori may not colonize the heterotopic gastric mucosa of Meckel's diverticulum and has no role in the development of ulceration at this site.

Pouchitis after ileal pouch-anal anastomosis: a Pouchitis Disease Activity Index.

OBJECTIVE: To develop a "Pouchitis Disease Activity Index" (PDAI) and to compare it with other diagnostic scoring systems for pouchitis. DESIGN: We compared patients who had an optimal outcome with those who had a poor result attributable to recurrent pouchitis after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis at the Mayo Clinic. MATERIAL AND METHODS: We evaluated the applicability of a PDAI that quantitated clinical findings and the endoscopic and histologic features of acute inflammation in four groups of patients: (1) 10 who underwent IPAA for ulcerative colitis and had symptoms compatible with a clinical diagnosis of pouchitis, (2) 5 who underwent IPAA for ulcerative colitis and did not have pouchitis, (3) 5 who underwent IPAA for familial adenomatous polyposis and had no symptoms of pouchitis, and (4) 5 who had a Brooke ileostomy for ulcerative colitis (control group). RESULTS: The PDAI was significantly greater in patients with the clinical features of pouchitis than it was for patients in the other three groups. All 10 patients with pouchitis fulfilled the PDAI criteria for a diagnosis of pouchitis; in contrast, only 1 of these 10 patients met the diagnostic criteria for pouchitis by application of previously established scoring systems. No asymptomatic patient qualified for a diagnosis of pouchitis by the PDAI criteria. CONCLUSION: The PDAI provides simple, objective, and quantitative criteria for pouch inflammation after IPAA and is more sensitive than prior scoring systems.

Scintigraphy of the whole gut: clinical evaluation of transit disorders.

OBJECTIVE: To describe an initial clinical experience with a noninvasive scintigraphic technique for assessing gastrointestinal motility. DESIGN: We studied gastric, small bowel, and colonic transit in 109 unselected patients encountered between June and December 1992 at the Mayo Clinic. MATERIAL AND METHODS: The study patients were categorized on the basis of major complaint (constipation in 46, upper gastrointestinal symptoms in 45, and diarrhea in 18) and presence or absence of an underlying organic disease. Radioscintigraphy was used to analyze various regions of the gastrointestinal tract; scans were obtained at 2, 4, 6, and 24 hours after ingestion of a radiolabeled test meal. RESULTS: Overall, patients with a main complaint of constipation usually had slow or normal gastric, small bowel, and colonic transit, whereas those with diarrhea as the major symptom usually had normal or fast results of these studies. In the 65 patients with no underlying organic disease, inconsistent patterns of gastric emptying and small bowel and colonic transit were noted. CONCLUSION: Our results suggest that this 24-hour scintigraphic test may be clinically useful in screening for dysmotility syndromes in patients with nausea, vomiting, diarrhea, or constipation.

Selective 5-hydroxytryptamine type 3 receptor antagonism with ondansetron as treatment for diarrhea-predominant irritable bowel syndrome: a pilot study.

Serotoninergic innervation may contribute to the control of colonic motility and to visceral sensation from the large bowel. Indeed, ondansetron hydrochloride, a selective 5-hydroxytryptamine type 3 receptor antagonist, has been shown to slow colonic transit in healthy volunteers. Thus, we wished to determine whether 5-hydroxytryptamine type 3 receptor blockade slows colonic and small bowel transit in patients with diarrhea-predominant irritable bowel syndrome (IBS) and whether symptoms would be ameliorated with drug therapy. Of 14 patients with well-established IBS who entered a randomized, double-blind, placebo-controlled crossover pilot trial of 4 weeks of treatment with ondansetron, 16 mg three times daily, 11 completed the study. A minimal "washout period" of 4 weeks (median, 7 weeks) separated the two phases of the trial because patients were required to have similar symptoms before both periods of the study. Colonic transit tended to be longer during drug therapy than during the placebo trial, but this difference was not significant. Small intestinal transit and orocecal transit were unchanged by the drug. The integrated and peak postprandial increases in neurotensin, peptide YY, and human pancreatic polypeptide in serum were not significantly different in the drug and placebo periods. After treatment with ondansetron, stool consistency improved significantly; however, stool frequency, stool weight, abdominal pain, and the symptom criteria for IBS were not significantly altered by the drug. The results of this pilot study suggest that the motor effects expected with 5-hydroxytryptamine type 3 receptor blockade (namely, slowed colonic transit) may be diminished in some patients with IBS. The subjective improvement in stool consistency may reflect changes in the perception of defecation.(ABSTRACT TRUNCATED AT 250 WORDS)

Campylobacter pylori and Barrett's esophagus.

Campylobacter pylori is thought to be confined to gastric mucosa; when detected in the duodenum in association with duodenal ulceration, the organism infects only areas of gastric metaplasia. Barrett's esophagus is a metaplastic condition of the esophagus, in which areas or islands of "gastric-type" epithelium are found. To determine whether C. pylori colonized the esophagus of patients with Barrett's esophagus, we studied retrospectively 23 unselected patients who had endoscopic and biopsy evidence of Barrett's esophagus. Mucosal biopsy specimens were stained by the Warthin-Starry silver technique and reviewed by an experienced, "blinded" histopathologist. Of the 23 patients, 12 (52%) had C. pylori in the esophagus. Patients with and those without C. pylori were of similar age and gender, had similar scores for acute and chronic inflammation, and had similar lengths of tubular esophagus with metaplastic gastric mucosa. These observations suggest that C. pylori commonly infects Barrett's esophagus. The clinical importance of this finding is unknown.