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.

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.

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.

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.

Short chain fatty acid rectal irrigation for left-sided ulcerative colitis: a randomised, placebo controlled trial.

BACKGROUND: Short chain fatty acid (SCFA) deficiency is associated with colitis in animals and humans, and the mucosal metabolism of these compounds is decreased in ulcerative colitis. AIMS: To assess the efficacy of topical SCFA treatment in ulcerative colitis. PATIENTS AND METHODS: 103 patients with distal ulcerative colitis were entered into a six week, double-blind, placebo controlled trial of rectal SCFA twice daily; patients who were unchanged on placebo were offered SCFA in an open-label extension trial. RESULTS: Of the 91 patients completing the trial, more patients in the SCFA treated than in the placebo treated group improved (33% v 20%, p = 0.14, NS). Those on SCFA also had larger, but statistically non-significant, reductions in every component of their clinical and histological activity scores. In patients with a relatively short current episode of colitis (< 6 months, n = 42), more responded to SCFA than to placebo (48% v 18%, p = 0.03). These patients also had larger, but statistically non-significant, decreases in their clinical activity index (p = 0.08 v placebo). Every patient who improved used at least five of six of the prescribed rectal SCFA irrigations, whereas only 37% who did not improve were as compliant. In the open-label extension trial, 65% improved on SCFA; these patients also had significant reductions (p < 0.02) in their clinical and histological activity scores. CONCLUSIONS: Although SCFA enemas were not of therapeutic value in this controlled trial, the results suggest efficacy in subsets of patients with distal ulcerative colitis including those with short active episodes. Prolonged contact with rectal mucosa seems to be necessary for therapeutic benefit.

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.

Highly variable gastric emptying in patients with insulin dependent diabetes mellitus.

Some diabetic patients--particularly those with nausea and vomiting--frequently have evidence of delayed gastric emptying while other diabetic patients may in fact exhibit accelerated gastric emptying. Whether the presence or absence of symptoms of upper gastrointestinal dysfunction correlated with objective measures of gastric emptying in insulin dependent diabetic subjects was investigated. Twenty one insulin dependent diabetic patients underwent a solid phase gastric emptying scintiscan using in vivo labelled chicken liver. Thirteen patients had symptoms suggestive of gastrointestinal dysfunction (nausea, vomiting, early satiety, or constipation), while eight patients had no gastrointestinal symptoms. Eleven patients had orthostatic hypotension. All patients had been diabetic since childhood or adolescence. As a group, the diabetic patients showed a half time (T50) of gastric emptying (mean (SD) 150.0 min (163.7) that was not significantly different from that of 12 healthy control subjects (148.1 min (62.4)). Those diabetic patients without gastrointestinal symptoms and without orthostatic hypotension, however, showed a gastric emptying half time (70.1 min (41.6)) that was significantly faster than that of the control subjects. Conversely, those diabetic patients with nausea, vomiting, and early satiety (or early satiety alone) showed T50 values that were significantly greater than those of the diabetic patients without these symptoms. No correlation was found between the T50 value and the duration of diabetes, the fasting blood glucose at the time of study, or the respiratory variation in heart rate (E:I ratio). These observations indicate that highly variable rates of gastric emptying occur in insulin dependent diabetic patients, and that accelerated gastric emptying may occur in diabetic patients who have no symptoms of gastrointestinal dysfunction.

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 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.

Gastrointestinal motor effects of erythromycin in humans.

The effects of an antibacterially effective IV dose of erythromycin on gastrointestinal motor activity were investigated in eight normal healthy human volunteers in the fasted state and the fed state. Motor activity was recorded by a multilumen manometric tube. Data were analyzed visually and by a computer method. Blood samples were obtained for erythromycin and motilin assays. In the gastric antrum, erythromycin significantly increased the total duration, amplitude, and area under contractions from 0 to 60 minutes and frequency of contractions from 0 to 30 minutes from the start of its infusion in the fasted state. A similar response in the fed state occurred mostly from 0 to 30 minutes after the start of erythromycin infusion. By contrast, erythromycin inhibited the frequency and decreased the duration of small intestinal contractions in the fed state but had no effect in the fasted state. The gastric motor response was related to the plasma concentration of erythromycin, but not to plasma motilin. Erythromycin significantly shortened the duration of migrating motor complex disruption by a meal. Erythromycin also induced symptoms of upper abdominal pain, bloating, and nausea. Abdominal pain was related to strong antral contractions in both fasted and fed states; bloating occurred only in the fed state. Nausea occurred in both fasted and fed states, but it was not related to any specific pattern of motor activity. It is concluded that the strong antral contractions induced by erythromycin may accelerate the rate of gastric emptying, but they may also be responsible for causing the sensations of upper abdominal pain and bloating. The motor response to erythromycin is less during the fed than during the fasted state. The strong antral contractions induced by erythromycin are not mediated by the release of motilin.

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.

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-).

Spatial and temporal patterns of human jejunal contractions.

We recorded human jejunal motor activity by a 12-lumen manometric tube with recording sites 2 cm apart. The contractile activity in the fasted and the fed state was analyzed by computer to define the spatial and temporal patterns of contractions. Mean duration and area of single contractions during phase III activity were not different from those during phase II activity. By contrast, the frequency and amplitude of contractions, their propagation distance, and the percentage of contractions that propagated for greater than or equal to 2 cm were significantly greater during phase III than during phase II activity. The mean frequency and percentage of propagated contractions in the fed state were intermediate between those during phase II and phase III activity. Mean propagation distance of postprandial contractions was not different from that of phase II contractions. Most contractions in the fed state were uncoordinated at adjacent recording sites. Occasionally, large-amplitude and long-duration contractions, called individual migrating contractions, propagated over long distances and frequently over the entire 22-cm study segment. We conclude that there are some significant differences between the spatial and temporal patterns of contractions between the fed state and phase II and phase III activity. The largely disorganized phasic contractions in the fed state may cause mostly mixing of the ingested meal and its slow distal propagation, whereas the infrequent individual migrating contractions may rapidly propel intestinal contents over longer distances.

D-glucose and L-leucine transport by human intestinal brush-border membrane vesicles.

This study utilized intestinal brush-border membrane vesicles obtained from organ donor intestine to characterize the absorption of D-glucose and L-leucine in the human intestine. Both D-glucose and L-leucine were taken up by sodium gradient-dependent active transport along the entire length of the small intestine. The relative magnitude of transport for both substrates under sodium gradient conditions followed the order distal jejunum greater than proximal jejunum greater than distal ileum. The number of carrier systems in these brush-border membrane vesicles was estimated by Eadie-Hofstee plot analysis. This analysis revealed that L-leucine was actively transported via a single high-affinity transport system for the length of the human small intestine. In contrast, the transport of D-glucose occurred via a high-affinity system along the length of the intestine and via a low-affinity, high-flux transport system that was limited to the proximal intestine. Both glucose transport systems were sodium dependent and phlorizin sensitive. The locations and apparent kinetic parameters of these transport systems indicated that these systems function efficiently in vivo as important mechanisms for carbohydrate and protein assimilation in humans. The presence of these active transport systems along the entire small intestine explains the formidable capacity for carbohydrate and protein assimilation in humans.

Treatment of diversion colitis with short-chain-fatty acid irrigation.

A condition known as diversion colitis frequently develops in segments of the colorectum after surgical diversion of the fecal stream; it persists indefinitely unless the excluded segment is reanastomosed. The disease is characterized by bleeding from inflamed colonic mucosa that mimics the bleeding of idiopathic inflammatory bowel disease, and it may culminate in stricture formation. We hypothesized that this condition is caused by the absence of luminal short-chain fatty acids, the preferred metabolic substrates of colonic epithelium. We studied four patients with diversion colitis, none of whom had evidence of Crohn's, idiopathic ulcerative, or infectious colitis. The excluded segment of the rectosigmoid contained negligible concentrations of short-chain fatty acids. When D-glucose was instilled, it did not undergo appreciable anaerobic fermentation. Instillation of a solution containing short-chain fatty acids twice daily resulted in the disappearance of symptoms and the inflammatory changes observed at endoscopy, over a period of four to six weeks. Remission has been maintained for up to 14 months (in one patient) by instillation daily to twice weekly. Administering enemas containing isotonic saline, or omitting treatment for periods of two to four weeks during the regimen, by contrast, did not produce any improvement or rapid relapse of the colitis. Histologic observation revealed a distinctive type of mucosal inflammation that resolved more slowly and less completely than the gross appearance of the inflamed mucosa. From these preliminary studies we infer that diversion colitis may represent an inflammatory state resulting from a nutritional deficiency in the lumen of the colonic epithelium, which is effectively treated by local application of short-chain fatty acids, the missing nutrients.