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Involvement of the gastrointestinal tract by Epstein-Barr virus--associated posttransplant lymphoproliferative disorders.

Posttransplant lymphoproliferative disorders (PTLD) are abnormal growths of lymphoid cells that occur in immunosuppressed organ transplant recipients. Most cases are of B-lymphocyte origin and are associated with Epstein-Barr virus infection. Twelve of 72 allograft recipients with PTLD in our series have had disease predominantly involving the gastrointestinal tract. The lesions are most often multiple and preferentially involve the distal small bowel. The appearance of the lymphoid cells ranges from nonuniform (polymorphic) to uniform (monomorphic). Most tumors contain a clonal component of B-lymphocytes, with or without a nonclonal background. Appropriate primary treatment includes surgical resection and reduction of immunosuppression. Occasional PTLD of the gastrointestinal tract do not respond to this regimen, these represent a more advanced state of tumor progression. Currently, 11 of 12 patients are alive 10-13 months after diagnosis. The surgical pathologist must be aware of the appropriate setting in which to consider a diagnosis of PTLD and be able to distinguish this condition from other lymphoproliferative disorders of the gastrointestinal tract.

Adolescent↗

The gastrointestinal tract as the portal of entry for foreign macromolecules: fate of DNA and proteins.

The gastrointestinal tract (GIT) of mammals is the main portal of entry for foreign DNA and proteins. We have documented the fate of orally administered DNA or protein in the GIT of the mouse. The gene for the Green Fluorescent Protein (GFP) (4.7 kb) and the genomes of bacteriophage M13 (7.25 kb) and adenovirus type 2 (Ad2; 35.9 kb) were used as test DNAs. Persistence of these DNAs in the GIT was monitored by Southern hybridization and fluorescent in situ hybridization (FISH) or by PCR. For studies on proteins, recombinant glutathione-S-transferase was fed to mice. Survival of the protein in the GIT was then assessed by Western blotting. Depending on feeding schedules and food regimens, but irrespective of mouse strain or DNA length, fragments of the GFP gene or other DNAs were detectable for up to 18 h after feeding by Southern blot analysis. The GFP DNA could be visualized by FISH in cecal epithelia. A high fiber diet reduced the time required for food to pass through the GIT, and foreign DNA was cleared more rapidly. A high fat diet or complexing of the foreign DNA with protamine or lipofectin did not extend DNA persistence times. Undegraded GST protein was detected only in foregut contents up to 30 min after feeding. At 15 and 30 min post feeding, trace amounts of GST were found in extracts of the kidney. The GIT is constantly exposed to highly recombinogenic fragments of foreign DNA and to intact foreign proteins. Our data have implications for studies on carcinogenesis and mutagenesis, and on the pathogenicity of infectious proteins such as prions.

Adenoviridae↗

Catamnestic investigations in children with malformations of the gastrointestinal tract and the abdominal wall.

Catamnestic investigations were performed in 288 children with malformations of the gastrointestinal tract and the abdominal wall, among them 41 with oesophageal atresia, 41 with stenosis/atresia of the small and large bowel, 78 with anorectal malformations, 75 with Hirschsprung's disease, 28 with omphalocele and 25 with gastroschisis. In atresias/stenoses of the gastrointestinal tract both sexes were equally affected whereas boys were significantly more often affected in both Hirschsprung's disease (p 0.0005) and omphalocele/gastroschisis (p 0.05). The babies were more frequently preterm (p 0.025) than it was the case in controls. Parental age was not higher than the average parental age at time of delivery. Incidence of malformations was significantly higher in the relatives of our patients than in the average population and reached 20% (p 0.0005) in relatives of children with omphalocele/gastroschisis. Teratogenic effects of alcohol, diseases, X-rays and drugs during pregnancy could be suspected in several instances, whereas adverse effects of smoking, previous abortions and cycle disorders before pregnancy could not be established.

Abdominal Muscles↗

Evaluation of flash echo imaging of the canine gastrointestinal tract.

Although it is important to assess gastrointestinal blood flow, no generally useful, noninvasive assessment method has been established. Harmonic flash echo imaging, which is an intermittent second harmonic imaging technique, has recently become available to evaluate blood flow. We investigated the usefulness of harmonic flash echo imaging in the assessment of the gastrointestinal tract, and we used this technique to study the effect of nicotine on small bowel blood flow. Harmonic flash echo imaging was performed at the beginning of intravenous injection of a contrast agent. It was also performed on the small bowel immediately before and 10 min after nicotine administration to evaluate blood flow. Gastric and small bowel walls were clearly enhanced on the primary images. Small bowel enhancement, which is regarded as transmural blood flow, significantly decreased after nicotine administration. Harmonic flash echo imaging appears to be useful in the assessment of the transmural blood flow in the gastrointestinal wall.

Animals↗

Effect of enzyme addition on the performance and gastrointestinal tract size of chicks fed lupin seed and their fractions.

Three experiments were conducted to study the effects of adding a crude enzyme preparation to diets containing whole, dehulled lupins and lupin hulls on performance, dry matter retention (DMR), AME, apparent protein digestibility (APD), and size of gastrointestinal tract of Leghorn and broiler chicks. In the first experiment, Leghorn chicks fed diets containing up to 70% whole lupins showed a depression in the performance. Progressive decreases in DMR (up to 30.2%), AME (up to 6.5%), and APD (up to 6.5%) and an increase in the relative gizzard weight (18.8%) were observed with increasing concentration of lupins (23.1, 46.9, and 70%) in the diet. Enzyme supplementation of diets containing lupins significantly improved the performance of the chicks. DMR and AME were improved by 4.2 and 3.1, respectively, and gizzard size was reduced (7.1%) by addition of the enzymes. In the second experiment, addition of 11.2 and 22.4% of lupin hulls to a dehulled lupin diet resulted in a dramatic depression in chick performance, with values ranging from 6.3% for feed consumption to 60.5% for fed to gain ratio, and an increase in the relative organ weight (up to 29.9%) and length (35.6%). These effects were partially counteracted by the action of enzymes. In the third experiment, increasing concentration of whole lupins (15, 35, and 45%) in broiler chicken diets caused a depression in the performance of birds fed 35 and 45% whole lupins as compared to those fed the wheat-soy diet. In contrast, 15% lupins improved weight gains compared to that obtained with the nonlupin diets. The lower content of lupins in the diet also had no or little effect on other performance values compared to the control group, whereas 35 and 45% dietary lupins tended to have negative effects. Likewise, increasing lupin content in the diet produced an enlargement in the relative size of several sections of the gastrointestinal tract. Enzyme supplementation of lupin diets improved weight gain (5.5%) and feed consumption (3.8%) with the values being similar to those obtained with the wheat-soy diet. Moreover, the enzymes also reduced the relative size of digestive organs from 5.3% for pancreas to 22.2% for crop. In summary, lupins appear to contain fibrous components that reduce the performance of the birds and increase the size of the gastrointestinal tract. The addition of enzymes counteracted these negative effects in birds fed whole, dehulled lupins and lupin hull diets.

Animal Feed↗

MRI of the gastrointestinal tract.

Magnetic resonance imaging (MRI) of the gastrointestinal tract may be useful for detection of inflammatory and neoplastic processes and staging of neoplasms. Successful application of MRI depends upon the use of proper gut contrast material, glucagon, and scan sequences that diminish the effect of respiratory motion. Current uses of MRI center on the evaluation and staging of rectal tumors and on the distinction between recurrent tumor and fibrosis.

Digestive System↗

Eicosanoids and the gastrointestinal tract.

Determining the role of eicosanoids in gastrointestinal physiology and pathophysiology has been an active area of investigation over the past 20 years. The landmark discovery of prostaglandin endoperoxide synthase and other enzymes involved in the production of arachidonic acid products (lipoxygenases and epoxygenases) ushered in a new era of research. The goal of this review is to distill a large body of work pertaining to studies of eicosanoids in the gastrointestinal tract. This review has been organized according both to functional (secretion and motility) and disease-related (inflammation, mucosal injury, and neoplasia) effects. The aim of this article is to present a clear summary of this area of gastroenterology so that future research can be directed in a logical and productive manner.

Anti-Inflammatory Agents, Non-Steroidal↗

Role of the gastrointestinal tract in burn sepsis.

During the last 50 years, our understanding of the role of the gastrointestinal tract as a first-line defense against the development of postburn sepsis has increased dramatically. Starting with the concept of that gut-derived bacteria cause distant injury, investigators have delineated a complex series of physical changes in the barrier of the gastrointestinal tract. Along with an understanding of these physical changes has come an appreciation of the role of the immune system in modulating postburn organ failure. Importantly, recent investigations into the role of mesenteric lymph have fundamentally changed the paradigm of organ failure and have implicated the gut as a cytokine-secreting organ. This article traces the development of key concepts in the study of burn sepsis and their clinical implications.

Bacterial Translocation↗

Malignant lesions of the upper gastrointestinal tract.

For malignant tumours of the upper gastrointestinal tract, endoscopic ultrasonography is used to assess their depth of penetration, infiltration of neighbouring organs, and metastatic spread to regional lymph nodes. Our experience so far in 124 echo-endoscopic examinations shows that the superior resolution of endoscopic ultrasonography makes possible a very accurate assessment of the depth of penetration of the tumour, and of lymphatic spread to the regional lymph nodes in oesophageal carcinoma. An assessment of infiltrative growth and differentiation from early carcinoma remains problematic.

Duodenal Neoplasms↗

Ethanol metabolism in the gastrointestinal tract and its possible consequences.

Ethanol is oxidised not only in the liver, but also in the gastrointestinal tract. Although this ethanol metabolism is less than that of the liver, it has some important relevance with respect to the first pass metabolism of alcohol and to ethanol induced tissue toxicity. In the gastrointestinal tract, ethanol can be metabolised not only in the mucosal cell via alcohol dehydrogenase (ADH) and microsomal ethanol oxidising system (MEOS), but also in a great variety of bacteria. Depending on the gastrointestinal location, one or the other metabolic pathway of alcohol may be predominant. The metabolism of ethanol by gastric ADH, the so called first pass metabolism, influences ethanol blood concentrations not only in the portal vein and thus in the liver, but also in the systemic circulation. As gastric ADH activity is decreased in younger women, in the elderly, in the alcoholic, during fasting and after treatment with certain H-2-receptor antagonists, increased blood ethanol concentrations may occur in these situations after oral intake of ethanol. However, this first pass metabolism of alcohol is influenced not only by ADH activity but also by the speed of gastric emptying (e.g. slow gastric emptying leads to increased first pass metabolism). Finally, gastric morphology also determines first pass metabolism. Chronic atrophic gastritis and Helicobacter pylori associated gastric injury lead to a decrease of gastric ADH activity, and thus possibly to a decreased first pass metabolism of alcohol. In addition, the local production of acetaldehyde from ethanol in the oesophagus, where significantly more sigma-ADH is present, may contribute to tissue injury and this may lead to the well known ethanol associated oesophageal cancer development. Various isoenzymes of ADH exist in the colorectum and they are also capable of producing acetaldehyde in amounts sufficient to injure the mucosa. Besides ADH, the MEOS, a mixed function oxidase, also metabolises ethanol. This system is inducible by chronic alcohol consumption and is involved in the metabolism of various xenobiotics including drugs and procarcinogens. Thus, an increased activation of dietary procarcinogens by this enzyme system may also contribute to carcinogenesis in the alcoholic. Finally, a great variety of gastrointestinal bacteria are capable of metabolising ethanol to acetaldehyde. This is possibly of major importance in the colorectum where faecal bacteria, especially anaerobes in the rectum, can produce high amounts of acetaldehyde, and this correlates with mucosal hyperregeneration suggesting an acetaldehyde mediated mucosal damage.

Adult↗

Leiomyomas of the gastrointestinal tract.

Sixteen patients with leiomyoma of the gastrointestinal tract underwent operation and removal of their tumor during a four- and one-half-year period from January 1980 to July 1984. There were three esophageal, five gastric, two small bowel, four colon, and two anorectal leiomyomas. The majority of gastric leiomyomas presented with bleeding, as did half of the small bowel and colon cases. All were treated by excision without mortality. The various clinical presentations, evaluations, and choice of operative approach for this uncommon tumor are discussed.

Adult↗

Motility of the gastrointestinal tract and gallbladder during long-term total parenteral nutrition in dogs.

BACKGROUND: The motility of the gastrointestinal tract during total parenteral nutrition (TPN) remains poorly understood. The objective of this study was to determine the motility pattern not only in the gastrointestinal tract but also in the gallbladders of dogs maintained by TPN. METHODS: Central venous catheters were inserted through the external jugular vein of 5 dogs and 6 strain gauge force transducers were sewn to the stomach, small intestine, and gallbladder. Two weeks later, oral food was discontinued and motility was recorded for 24 hours after the first migrating motor complex (MMC) was confirmed in the stomach as pre-TPN. TPN was started and continued for 4 weeks, and patterns of motor activity during TPN were recorded for 24 hours at the end of each week. RESULTS: The durations of MMC in the stomach, duodenum, and gallbladder in pre-TPN were 118 +/- 3 minutes, 118 +/- 2 minutes, and 118 +/- 2 minutes, respectively, but in the first week of TPN they were 432 +/- 56 minutes, 431 +/- 56 minutes, and 386 +/- 29 minutes, respectively. TPN times were significantly longer than those of pre-TPN (corrected p < .005). The durations of MMC in jejunoileum did not alter between pre-TPN and TPN. The occurrences of phase III in the stomach, duodenum, and gallbladder in pre-TPN were 12/d, but during TPN they were reduced significantly (corrected p < .005). CONCLUSIONS: TPN did not affect the motility of the jejunoileum but did inhibit the motor activities of the stomach, duodenum, and gallbladder. The inhibition of gallbladder contraction observed during TPN may be one of the factors inducing gallbladder disease.

Animals↗

A new method for visualization of gut mucosal cells, describing the enterochromaffin cell in the rat gastrointestinal tract.

OBJECTIVE: Enterochromaffin (EC) cells in the gastrointestinal tract have an important function as regulators of secretion, motility and sensation. The EC cell has traditionally been described as bottle-shaped, with basally located stores of serotonin. Stimuli acting on the apical membrane trigger serotonin release, which in turn activates the subepithelial sensory nerve terminals. To better describe the appearance of EC cells, we developed a new method for visualization of mucosal cells. MATERIAL AND METHODS: The stomach, small intestine and large intestine were excised from Sprague-Dawley rats and then fixed in formalin. The organs were everted and filled with pronase solution. Single cells and aggregates of formalin-fixed mucosal cells were collected by scraping the mucosa off the muscularis mucosa. EC cells were visualized by staining for immunoreactivity against serotonin. RESULTS: EC cells with luminal extensions and very long (up to 80 microM) basally located axon-like extensions, sometimes connecting to neuron-like structures, were found. Other EC cells had no or only short and blunt basal extensions. Dividing serotonin-containing EC cells were also seen. CONCLUSIONS: These findings could make an important contribution towards furthering our understanding of EC cell function in gastrointestinal physiology. This new method can also readily be used to give better visualization of the morphology of other mucosal cells.

Animals↗

Metastatic melanoma of the gastrointestinal tract. Results of surgical management.

Between 1954 and 1989, 41 patients with melanoma metastatic to the gastrointestinal tract underwent surgical treatment at the Mayo Clinic, Rochester, Minn. The small bowel was most commonly involved (71%), followed by the stomach (27%), large bowel (22%), and esophagus (5%). Gross total excision of all intra-abdominal metastases was performed in 52% of patients. The postoperative mortality was 5% and the median patient survival was 0.8 years, with 1- and 5-year survival rates of 44% and 9%, respectively. Of the patient, tumor, and treatment variables evaluated, patients with small-intestinal metastases had a significantly worse prognosis. Although patients with melanoma metastatic to the bowel have a limited life expectancy, surgical resection of their metastases provides effective palliation. Operative treatment of selected patients with symptomatic melanoma metastatic to the gastrointestinal tract is a worthwhile undertaking.

Adult↗

Comparison of vascular response of different locations of the gastrointestinal tract to isoproterenol and nifedipine.

In the present study we have compared the effect of intravenous infusion of a calcium channel blocker, nifedipine (1.0 micrograms.kg-1.min-1 for 20 min), with that of isoproterenol (0.1 micrograms.kg-1.min-1 for 20 min) on the hemodynamic parameters and the vascular response of different locations and tissue layers of the gastrointestinal tract. Heart rate increased with isoproterenol but not with nifedipine. Both agents caused a similar increase in cardiac output and a similar fall in mean arterial pressure. After 20 min infusion, nifedipine increased the blood flow of the axillary artery, but isoproterenol had no such effect. Isoproterenol caused vasodilation of the mucosa in the antrum but not in the fundus and the body of the stomach or in the duodenum, jejunum, mid small intestine, ileum, and colon. The mucosal effect of nifedipine was similar, except that it also caused vasodilation in the small bowel and in the ascending colon. Nifedipine caused vasodilation of the muscularis throughout the gastrointestinal tract, but isoproterenol had no such effect. These differences are discussed in relation to the mechanism of action of these two vasodilators. It is suggested that the vascular response of different locations and tissue layers of the gastrointestinal tract to vasodilators is locally regulated by a variety of mechanisms may include beta- and alpha-receptor density and (or) sensitivity, angiotensin II activity, and metabolic need of the tissues.

Animals↗

Mitochondrial inclusions in human cancer of the gastrointestinal tract.

Four cases of adenocarcinoma of the gastrointestinal tract have been examined. Large electron-dense mitochondrial inclusions were found in the mitochondria of many cells; after detailed histochemical tests they could be classified into two types. The first type of inclusion consisted of clusters of electron-dense, calcium-containing granules linked to a glycoproteic substrate. These inclusions were linked to a glycoproteic substrate. These inclusions were always associated with cristae and were found in the mitochondria of cells that showed clear signs of degeneration. The second type of inclusion was found much more frequently and consisted essentially of phospholipids of which electron density was strictly osmium dependent. Their structure was usually at least partly lamellar, but in some cases it was homogeneous throughout. It is hypothesized that inclusions of the second type may have the same biological role as the morphologically identical inclusions found in the mitochondria of brown fatty tissue in the perinatal rat and in yeasts during glucose repression or anaerobiosis. The resemblance between the homogeneous variety of inclusions within the second type and the mitochondrial inclusions recently described in human leukemic lymphoblasts and monoblasts has been stressed to bring out the need for a histochemical check on the supposedly viral nature of the latter inclusions.

Adenocarcinoma↗

Pharmacological properties of Ciloprost, a stable prostacyclin analogue, on the gastrointestinal tract.

The effect of Ciloprost on the gastrointestinal tract was studied in rats and compared with prostacyclin (PGI2) and/or PGE2. In the anaesthetized rat continuous i.v. infusion of Ciloprost decreased pentagastrin stimulated gastric acid secretion with the same potency [ED 50 -35 micrograms/(kg x h)]as PGI2 [ED 50 -42 micrograms/(kg x h)]. In the pylorus-ligated rat Ciloprost reduced acid secretion with an ED50 of about 6.4 mg/kg p.o. whereas PGE2 and PGI2 were ineffective during submaximal stimulation of acid secretion by pentagastrin. In the same experimental design continuous i.v. infusion of Ciloprost and PGI2 caused 50% reduction in gastric acid output with doses of 80 and 24 micrograms/(kg x h), respectively. Ciloprost prevented indomethacin-induced gastric erosions at an ED50 of 60 micrograms/kg p.o., compared to 10 micrograms/kg p.o. of PGE2, whereas PGI2 showed only weak cytoprotective activity. The stable prostacyclin analogue inhibited castor oil induced enteropooling with a 4-5 fold higher potency than PGI2 and delayed castor oil induced diarrhoea more effectively than its natural counterpart. Intestinal motility was strongly reduced by both PGI2 and Ciloprost. Gastric emptying was also reduced after PGI2 and Ciloprost administration, with a 4-5 fold higher activity of the stable analogue. The present results demonstrate, that Ciloprost shows a biological profile similar to that of PGI2.

Animals↗

Receptor binding sites for substance P and substance K in the canine gastrointestinal tract and their possible role in inflammatory bowel disease.

The mammalian tachykinins, substance P, substance K (neurokinin A) and neuromedin K (neurokinin B), are putative peptide neurotransmitters in both the brain and peripheral tissues. We used quantitative receptor autoradiography to localize and quantify the distribution of binding sites for radiolabeled substance P, substance K and neuromedin K in the canine gastrointestinal tract. Substance P binding sites were localized to smooth muscle cells in the muscularis mucosa and muscularis externa, the smooth muscle and endothelium of arterioles and venules, neurons in the myenteric plexus, mucosal epithelial cells, exocrine cells and lymph nodules. Substance K binding sites were distributed in a pattern distinct from substance P binding sites and were localized to smooth muscle cells in the muscularis mucosa and muscularis externa, the smooth muscle and endothelium of arterioles and venules, and neurons of the myenteric plexus. Neuromedin K binding sites were not observed in any area of the canine gastrointestinal tract although they were localized with high specific/non-specific binding ratios in the canine spinal cord. These results indicate that there are at least two distinct types of tachykinin receptor binding sites in the canine gastrointestinal tract, one of which probably recognizes substance P and the other substance K as endogenous ligands. In correlation with previous physiological data, these substance P and substance K receptor binding sites appear to be involved in the regulation of a variety of gastrointestinal functions including gastric motility, mucosal ion transport, hemodynamics, digestive enzyme secretion and neuronal excitability. In addition these results demonstrate that receptor binding sites for substance P and substance K are expressed by cells involved in mediating inflammatory and immune responses. These data, together with our studies on surgical specimens from patients with inflammatory bowel disease, suggest that in a pathophysiological state tachykinins and their receptors may play a role in inflammatory bowel disease and should permit a rational approach to designing neuropeptide antagonists which may prove effective in treating inflammatory diseases.

Animals↗