Effect of antidiuretic hormone on human small intestinal water and solute transport.

The effect of i.v. Pitressin (ADH) in a dose of 1 U/hr on permeability characteristics and on absorptive capacity of the normal human small intestine was investigated. The method of continuous intestinal perfusion was employed with polyethylene glycol 4000 as a nonabsorbable marker. Unidirectional flux rates of Na and H(2)O were calculated from the disappearance of (22)Na and of (3)HOH from isotonic saline solution within the intestinal lumen. Each study consisted of two successive perfusion periods: one while the subject was hydrated, the other during ADH infusion or while the subject was dehydrated. Water and sodium absorption from isotonic NaCl occurred in the hydrated state and was abolished by ADH as well as by dehydration in the jejunum. In some instances, net gain of water and sodium in the lumen occurred. In the ileum, ADH and dehydration caused a decrease in water and sodium absorption rate. By contrast, unidirectional flux into the intestinal lumen of water and sodium, as well as dextrose and D-xylose diffusion, remained unchanged by ADH. During perfusions with hypertonic urea solutions the rates of sodium and water entry into the intestine were greatly increased during i.v. ADH infusion, whereas urea loss from the study segment remained constant. ADH in the dosage used did not affect human intestinal motility. The results suggest that circulating ADH in physiologic concentrations affects the small intestine in one of two ways: increased secretion of water and salt into the lumen or direct interference with the active sodium transport mechanism.

The effect of short chain fatty acids on transmural electrical potential across rat small intestine in vivo.

Short chain fatty acids suddenly produce a phasic increase in transmural electrical potential difference (PD) when placed in the lumen of rat small intestine in vivo. With concentrations of propionate ranging from 50 muM to 1000 muM the amplitude of the response in jejunum is about 5.5 mV. The concentration giving half this effect is about 20 muM. With 10 mM propionate the duration of the response is 3-5 min; after this, PD again equals the control value and the gut is refractory to further additions. Removing propionate from the mucosal surface produces no change in PD, but does restore responsiveness to subsequent exposure to short chain fatty acids. This effect is independent of a variety of other alterations in PD such as those caused by sugars, amino acids, bile salts, theophylline, prostaglandins, and ATP. Mechanism and significance of this surprisingly sensitive response remain obscure.

Acute effect of clonidine on gastric emptying in patients with diabetic gastropathy and controls.

BACKGROUND: The treatments available for diabetic gastropathy are frequently ineffective. Clinical observations suggest that clonidine, an a-2 adrenergic agonist, may improve diabetic gastropathy symptoms. AIMS: To establish whether a single oral dose of clonidine alters the gastric emptying of a solid meal in 10 patients with diabetic gastropathy and their matched controls. A secondary goal was to compare two methods of analysis of the data from gastric emptying studies. METHODS: Clonidine, 0.3 mg, or a matched placebo were administered orally in a double-blind fashion. RESULTS: Only three of the 10 patients showed an increased gastric residual volume. Gastric emptying rates were comparable in patients and controls. Clonidine had no significant effect on gastric emptying in the controls but increased t1/2 values in the patient group. This effect just reached statistical significance only when calculated by the power exponential method (P=0.05 but not by the linear component model. CONCLUSIONS: Delayed gastric emptying is not an invariable characteristic of symptomatic diabetic gastropathy. Clonidine, given as a single dose of 0.3 mg orally, has no gastric prokinetic effects. It may act on gastric afferent innervation or, more likely, at a central site to reduce nausea and vomiting. The analysis of gastric emptying data by the power exponential and the two linear component methods yields equivalent results.

Hormone producing pancreatic islet cell carcinoma: changing clinical presentation.

A patient with pancreatic islet cell carcinoma demonstrated spontaneous remission and recurrence of hyperinsulinism and disappearance of elevated plasma motilin levels. Despite evidence for gastrin production by the tumor initially, the Zollinger-Ellison syndrome was not diagnosed until three years after initial presentation. Diarrhea and steatorrhea could be attributed to hyperchlorhydria rather than to direct intestinal effects of elevated cirulating gastrin, gastric inhibitory peptide or motilin. Pancreatic islet cell carcinomas, considered as a type a APUD cell proliferation, frequently produce more than one hormone; the pattern of hormone secretion may differ with time and clinical manifestations may change accordingly.

[Diagnostic guidelines in diarrhea]. / Diagnostischer Leitfaden bei Diarrhoe.

Acute diarrhea is usually short-lasting; therefore, diagnostic procedures are mainly concerning the degree of dehydration. With longer duration of high fever or bloody diarrhea, microbiologic stool tests are necessary. Proctosigmoidoscopy is indicated in case of dysenteric disease or suspected antibiotic-as-associated pseudomembranous colitis. In chronic diarrhea, the most important diagnostic procedure is a careful history. Side effects of drugs and food-related causes are especially noticeable, as are indices of an organic origin, e.g. unwanted weight loss or blood in the stools. Also, careful history and physical examination are essential for the decision about laboratory tests, tests of gastrointestinal function or endoscopy.

Nongranulomatous chronic idiopathic enterocolitis: a primary histologically defined disease.

Nongranulomatous chronic idiopathic enterocolitis is characterized by sudden onset of severe watery diarrhea, malabsorption, exudative enteropathy, frequent appearance of shallow ulcerations, and variable degrees of villus atrophy. In the absence of infectious and pharmacologic causes, the presence of a predominantly acute inflammatory infiltrate limited to the lamina propria establishes the diagnosis. No underlying disease appears during prolonged follow-up. The etiology remains unknown. The disease is generally corticosteroid-responsive; low-dose maintenance therapy is frequently required. The long-term prognosis is guarded. Three of 11 patients died of opportunistic infections or resistance to therapy.

Colonic fermentation: metabolic and clinical implications.

Colonic SCFA formation from fermentable carbohydrate is important for the maintenance of morphologic and functional integrity of the colonic epithelium. Carbohydrate-induced diarrhea occurs when the amount of carbohydrate entering the colon exceeds its fermentation capacity. Deficient availability or utilization of SCFA, mainly of n-butyrate, is the cause of diversion colitis and may play important roles in colonic carcinogenesis, in starvation and enterotoxigenic diarrhea, and in idiopathic UC.

[Diagnostic approach to the patient with malabsorption (author's transl)]. / Diagnostische Taktik beim Patienten mit Malabsorption.

Malabsorption is eminently treatable, by specific therapy of the underlying disease in the majority of cases, or, at least, by correction of developing nutritional deficiencies. We, therefore, owe our patients that we will not rest until a diagnosis is established. The large majority of patients can be diagnosed with techniques available to most practicing physicians and general hospitals. In the rare instance where a diagnosis cannot be reached, the physician should not hesitate to refer the patients to a center spezializing in gastrointestinal diseases.

Therapeutic endoscopy.

Therapeutic endoscopy of the GI tract is emerging as a new discipline. Its use for such procedures as foreign body removal, polypectomy, and papillotomy is widely accepted, but newer applications--including endoscopic hemostasis and injection sclerotherapy of esophageal varices--are still controversial. An overview of therapeutic guidelines and state-of-the-art technique is presented.

Nausea and vomiting in the diabetic patient.

The nausea and vomiting that can complicate advanced diabetes is often attributed to impaired gastric motility. Not all patients with diabetic gastropathy show marked abnormality on gastric emptying studies, however. The mechanism remains uncertain, although cases complicated by a bezoar may respond to its removal. Prokinetic drugs may bring a measure of relief, albeit often temporary.

Lithotripsy versus cholecystectomy for management of gallstones. A decision analysis by Markov process.

Extracorporeal shock-wave lithotripsy is a new treatment method that effectively distintegrates radiolucent gallstones and is associated with a low complication rate. Using the model of a Markov process for decision analysis, survival and costs under four possible strategies to treat gallstones were compared: expectant management with cholecystectomy (EC) or lithotripsy (EL) reserved for symptomatic gallstones; prophylactic cholecystectomy (PC) or lithotripsy (PL) for all gallstones. Life expectancy for the different strategies varies by few days. Only if high annual rates of pain and complication occurred in subjects with silent gallstones would both prophylactic procedures marginally increase life expectancy. Prophylactic cholecystectomy then would be more cost-effective than prophylactic lithotripsy. Expectant strategies remain much cheaper than prophylactic management over a broad range of probability values and procedural costs. Expectant use of lithotripsy costs less than cholecystectomy. A low success rate of lithotripsy would raise the direct costs of lithotripsy above those of cholecystectomy but leave total costs of both strategies in the same order of magnitude. Lithotripsy appears to be a feasible alternative to treat symptomatic but not asymptomatic gallstones.

Cryptosporidiosis and inflammatory bowel disease. Experience from the Milwaukee outbreak.

The 1993 Milwaukee Cryptosporidium outbreak posed several questions regarding appropriate management and prognosis of inflammatory bowel disease patients acutely infected with this organism. We prospectively identified and monitored 12 patients with stable ulcerative colitis or Crohn's disease who suffered abrupt clinical decompensation during the outbreak. All recovered to baseline at < or = 60 days. In patients receiving immunosuppressive therapy, mean duration of symptoms was no longer than in patients without it. Antibiotics did not clearly reduce duration of illness. Two additional patients without a history of intestinal disease presented with ileitis and colitis, respectively, initially suggesting Crohn's disease. Both recovered completely without specific therapy. We conclude that cryptosporidiosis may present as an acute relapse of inflammatory bowel disease and responds to standard therapy; antibiotics confer no obvious benefit. Immunosuppressive therapy does not predispose to chronic or severe illness in these patients. Cryptosporidiosis may present with acute findings initially mimicking Crohn's disease.

Absorption of short chain fatty acids from the human jejunum.

Jejunal absorption of acetate, propionate, and butyrate--the three predominant short chain fatty acids (SCFA's) in small and large intestinal contents--was studied in 5 volunteer subjects. A triple-lumen perfusion technique was employed; the test solutions were isotonic and contained 0, 5, 10, 25, 40, or 50 mM of a SCFA as the sodium salt. Intermittent secretion of small amounts of acetate and butyrate occurred during 3 of 15 control perfusion periods, and the concentrations measured in intestinal samples exceeded those reported for circulating plasma. The three SCFA's were absorbed rapidly and at equal rates. Absorption rates rose in apparently linear fashion with the mean concentration in the study segment (up to 20 mM) but reached saturation at the higher concentrations present in the mixing segment. Water and sodium absorption increased slightly during butyrate absorption. The flow rate of fasting intestinal contents did not increase during SCFA perfusion. SCFA's are readily absorbed and do not exert a diarrheogenic effect in the normal human jejunum.

Transport of propionate by human ileal brush-border membrane vesicles.

Human ileal brush-border membrane vesicles were employed to study the mechanisms of short-chain fatty acid (propionate) absorption especially to determine the effects of intravesicular HCO3- and the component of nonionic diffusion. Preloading the vesicles with HCO3- resulted in up to 20-fold "overshoots" of transport, and this effect was not seen with other intravesicular anions. This transport process was very fast (peak uptake 6 s) and was not due to intravesicular buffering by HCO3-. Radiolabeled propionate transport demonstrated transstimulation when the vesicles were preloaded with unlabeled propionate. An inward H+ gradient led to stimulation of propionate transport much smaller than in the presence of trans-HCO3-, whereas an inward Na+ gradient had no effect. Propionate transport was attenuated by the anion exchange inhibitors SITS and DIDS. Under HCO3- gradient conditions, propionate transport exhibited saturation kinetics with an apparent Km of 21 +/- 3 mM and a Vmax of 50 +/- 3 nmol.mg protein-1.3 s-1. Propionate transport was inhibited up to 40% by 2-5 carbon short-chain fatty acids (10 mM) but not by other organic anions. Short-chain fatty acid transport in the human ileum is Na+ independent and occurs mostly via a specific anion exchange mechanism with HCO3-. Our results also demonstrate a small component of nonionic diffusion of the protonated fatty acid (or anion exchange for OH-).

Brush border membrane vesicles formed from human duodenal biopsies exhibit Na+-dependent concentrative L-leucine and D-glucose uptake.

The human duodenum actively transports L-leucine and D-glucose under Na+ gradient conditions as demonstrated by uptake studies using brush border membrane vesicles from organ donor duodenum. Brush border membrane vesicles formed from peroral duodenal biopsies likewise demonstrate Na+ dependent concentrative uptake of D-glucose and L-leucine. This is the first demonstration of active transport processes in human duodenum. A simple microvesiculation method to form these vesicles is described as well as its potential application to clinical medicine in studying diseases of defective intestinal transport.

Nongranulomatous chronic idiopathic enterocolitis: clinicopathologic profile and response to corticosteroids.

BACKGROUND & AIMS: Nongranulomatous ulcerative enterocolitis has been reported in association with celiac sprue, lymphoma, and hypogammaglobulinemia. The objective of this study is to present evidence that this disorder exists as a primary entity. METHODS: The medical records and histological material of 9 patients (mean age, 45.7 +/- 5.9 years) who presented with severe chronic diarrhea without specific diagnosis after extensive investigations were reviewed. RESULTS: Endoscopically, the duodenum and proximal jejunum were inflamed in 6 of 7 patients, with superficial ulcerations in 5 patients. On histology, the lamina propria was infiltrated by polymorphonuclear and chronic inflammatory cells, with varying degrees of villous atrophy. There were no significant cellular abnormalities of the epithelial enterocytes. A similar inflammatory infiltrate was present in the colon in 4 or 5 patients. Eight of 9 patients responded to corticosteroids with clinical and variable histological improvement. Four patients developed bleeding from ulcerations in the small or large intestine. Three patients died: 1 patient who did not respond to treatment with corticosteroids and 2 patients with systemic infection. Four of the 6 surviving patients required maintenance low-dose corticosteroid therapy. No underlying disease was discovered during prolonged follow-up. CONCLUSIONS: Idiopathic nongranulomatous enterocolitis may present as a primary, frequently fatal disease. Corticosteroid therapy provides immediate benefit and may be required indefinitely.

The short-circuited everted sac of rat colon mucosa.

A short-circuited preparation of everted rat colon sacs is described. The serosal current electrode is a AgAgCl wire. A cylindrical agar bridge or AgAgCl electrode may be employed on the mucosal side. Effects of Ag+ ions liberated from the electrodes on ion transport could not be demonstrated. Fluid and sodium are absorbed ad bicarbonate secreted. Potassium and chloride movements are not significantly different form zero. The preparation remains stable for at least 2 h. Sodium absorption is diminished by 50% and bicarbonate secretion abolished in the absence of glucose. In principle, similar ion transport properties were found as in Ussing-chamber preparations. The advantage of the everted sac is the capability of measuring net transport of fluid and electrolytes simultaneously and directly because of the large surface/inner volume ratio of the sac.

Absorption of short-chain fatty acids by the colon.

Short-chain fatty acids (SCFAs) constitute the major solute fraction of normal stool water and are responsible for the diarrhea associated with carbohydrate (CHO) malabsorption. Although SCFA absorption from the human small bowel has been reported previously, the fate of SCFAs in the colon--their major site of production--was investigated in the present study. The colon of normal volunteers was perfused with neutral, isotonic solutions containing SCFA, 0-90 mM. Propionate was studied in detail with limited observations on acetate and n-butyrate. SCFA absorption was concentration-dependent; back diffusion of metabolic products, ketone bodies, was quantitatively insignificant. The transport process was accompanied by increased Na, K, and water absorption, by luminal alkalinization due to bicarbonate accumulation, and by a fall in lumen PCO2. The results are consistent with the existence of two mechanisms for colonic SCFA absorption: first, nonionic diffusion of protonated SCFA involving consumption of luminal CO2; this process accounts for about 60% of total SCFA absorption; and second, cellular uptake by ionic diffusion of the Na or K salt of the SCFA.

Effect of insulin, glucose, and controlled diabetes mellitus on human jejunal function.

The effects of serum insulin concentration, serum glucose concentration, and of insulin-dependent diabetes mellitus on human jejunal glucose, Na, and H2O absorption were assessed. Triple-lumen perfusion studies were carried out in 20 nondiabetic and 9 insulin-requiring diabetic male volunteers. In seven normal subjects, sequential elevation of serum insulin concentrations from 20 muU/ml to 50 and 100 muU/ml for 2 h each, with maintenance of constant serum glucose levels, failed to significantly alter glucose, Na, and H2O absorption. Absorption of glucose, Na, and H2O was similar when the serum glucose concentration was maintained at 125 and at 250 mg/100 ml. Glucose absorption results during 26 perfusion studies in 20 control subjects were compared with results obtained during 20 perfusion studies in 9 diabetic subjects. Glucose concentrations in isotonic perfusates were 25, 40, or 75 mM. Na and H2O absorption rates were similar in both groups. Regression lines relating glucose load or geometric mean study segment glucose concentration to glucose absorption were also comparable. These results indicate that insulin-requiring diabetics absorb glucose, Na, and H2O normally.