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Epithelial restitution in the gastrointestinal tract.

Injury to the gastrointestinal mucosa can be divided into two types: (a) deep injury involving extensive hemorrhage and large areas of tissue necrosis, and (b) superficial injury confined to the upper regions of the mucosa and not involving hemorrhagic lesions. Mucosal repair differs according to the severity of the damage. Repair of deep injury takes weeks because large regions of the mucosa must be replaced with new tissue, a process involving mitosis. Superficial injury is initially repaired rapidly over hours by epithelial restitution that does not involve mitosis but proceeds in the following sequence of events: First, the damaged surface epithelial cells are shed and form a layer that protects the restituting mucosa. Then the viable epithelial cells that remain attached to the mucosa at the margin of the wound become flattened and rapidly migrate over the denuded basal lamina. The superficial epithelium is re-established when migrating cells touch, form new tight junctions, and repolarize their organelles. This rapid protective mechanism, called restitution, has recently been documented in the stomach, duodenum, colon, and rectum. The cellular mechanisms, speed of migration, recovery of transmucosal electrical potential difference, and specific peculiarities of rapid epithelial restitution in the various regions of the gastrointestinal tract are reviewed here.

Animals↗

Toothpick injuries to the gastrointestinal tract.

Perforation of the gastrointestinal tract by toothpicks is an uncommon but well described occurrence. Five cases treated by the authors over the past 5 years are described. This series emphasizes the fact that plain abdominal and chest radiology is unhelpful in establishing the diagnosis. Risk factors identified are the wearing of dentures and previous abdominal surgery.

Adult↗

Potential role of epithelial cell-derived histone H1 proteins in innate antimicrobial defense in the human gastrointestinal tract.

In the human gastrointestinal tract, microorganisms are present in large numbers in the colon but are sparse in the proximal small intestine. In this study, we have shown that acid extracts of fresh human terminal ileal mucosal samples mediate antimicrobial activity. Following cation-exchange chromatography, one of the eluted fractions demonstrated antibacterial activity against bacteria normally resident in the human colonic lumen. This activity was further fractionated by reverse-phase high-performance liquid chromatography and identified as histone H1 and its fragments. We have also shown that in tissue sections, immunoreactive histone H1 is present in the cytoplasm of villus epithelial cells. In vitro culturing of detached (from the basement membrane) villus epithelial cells led to the release of antimicrobial histone H1 proteins, while the cells demonstrated ultrastructural features of programmed cell death. Our studies suggest that cytoplasmic histone H1 may provide protection against penetration by microorganisms into villus epithelial cells. Moreover, intestinal epithelial cells released into the lumen may mediate antimicrobial activity by releasing histone H1 proteins and their fragments.

Amino Acid Sequence↗

Crohn's disease of the upper gastrointestinal tract.

Although Crohn's disease (CD) is generally found in the ileum and/or colon, since the 1960s it has become evident that this chronic inflammatory disorder of unknown aetiology can affect the whole gastrointestinal tract from mouth to anus. In 0.5-13% of patients with ileocolonic CD the disease occurs in the upper gastrointestinal tract as well (i.e., from mouth through jejunum). With the radiological double-contrast technique, however, early signs of upper gastrointestinal CD may be detected in 20-40% of patients with ileocolitis. On the other hand, histologically evaluated biopsies from the lower oesophagus, body of the stomach, gastric antrum and the duodenal bulb of patients with Crohn's disease from whom the upper gastrointestinal tract is normal, according to X-ray or endoscopy may reveal lesions, which are considered to be pathologically diagnostic. Jejunal involvement occurs in 4-10% of patients with ileitis, ileocolitis or colitis. In early studies biopsies of apparently normal buccal mucosa from patients with Crohn's disease showed a significant correlation between the activity of the disease, as defined by the Crohn's Disease Activity Index, and the number of plasma cells containing IgM, suggesting a generalized activated humoral defence system during relapse. A diagnosis of Crohn's disease of the upper gastrointestinal tract can be achieved by combining recognition of clinical, roentgenographic, and endoscopic features. Provided that other causes of granulomatous involvement of the gastrointestinal tract can be excluded, non-caseating granulomas are generally accepted as the histological proof of Crohn's disease. When Crohn's disease does involve the upper gastrointestinal tract, there is nearly always concomitant disease in the small bowel or colon. Compared to patients with an ileocolonic localization, patients with Crohn's disease in the upper gastrointestinal tract more frequently have colic-like abdominal pain and/or cramps, nausea and anorexia as presenting symptoms and are younger at onset of the disease. Medical therapeutic principles are the same as for Crohn's disease elsewhere in the gastrointestinal tract. Absolute indications for surgical treatment are massive bleeding, progressive stenosis, and extensive fistula formation.

Crohn Disease↗

Artificial ascites technique for percutaneous radiofrequency ablation of liver cancer adjacent to the gastrointestinal tract.

BACKGROUND: Percutaneous radiofrequency ablation (RFA) of liver tumours adjacent to the gastrointestinal tract is controversial. This study assessed the value of an intraperitoneal water infusion (artificial ascites) technique for percutaneous RFA of such tumours. METHODS: Before ablation in 52 patients (55 treatments, 58 tumours), between 250 and 3000 (mean 681) ml 5 per cent glucose solution was infused into the abdominal cavity using a 14-G needle, with the aim of preventing thermal injury by separating the liver from the gastrointestinal tract. RESULTS: There were no adverse events associated with the artificial ascites technique. In 43 (78 per cent) of the 55 treatments, the liver and gastrointestinal tract were separated successfully. In the other 12 treatments, in which the separation was not confirmed by real-time ultrasonography, there was one case of perforation of the ascending colon after RFA; adhesion of the liver and colon resulting from previous laparotomy may have been related to the injury. CONCLUSION: Production of artificial ascites can be undertaken safely, making RFA safe and effective for hepatic tumours adjacent to the gastrointestinal tract. In patients with possible postoperative adhesions, confirmation of separation of the liver from surrounding organs is mandatory to avoid thermal injury.

Aged↗

Postoperative gastrointestinal tract dysfunction.

Postoperative gastrointestinal (GI) tract dysfunction (PGID) is common and is associated with increased patient suffering and cost of care. The pathogenesis of PGID is complex and multifactorial. Traditional measures intended to reduce the incidence of PGID, such as the use of prokinetic drugs, nasogastric tube drainage, and the avoidance of early fluid and/or food intake, are apparently not beneficial. The administration of larger volumes of IV fluids to achieve predetermined increases in cardiac output has been shown in randomized trials to improve gut perfusion and reduce the incidence of PGID. A multimodal approach that includes limited surgical incision, regional local anesthesia, early mobilization, and enteral feeding has been associated with a dramatic reduction in postoperative complications, PGID, and length of hospital stay. However, none of these approaches has been validated in adequately powered multicenter prospective randomized controlled trials.

Anesthesia↗

Structural aspects of blood group glycosphingolipids in the gastrointestinal tract.

The epithelial cells of the gastrointestinal tract from different species show a very variable expression of blood group active glycosphingolipids. The core saccharide sequences are typical for the species as, for example, type 1 chains (Gal beta 1----3GlcNAc) are found in the small intestine of man, rat, and pig and type 2 chains (Gal beta 1----4GlcNAc) are found in the small intestine of dog, rabbit, and cat. The mouse is atypical with the ganglioseries as the major core saccharide of the small intestine. Blood group A determinants can be found in the small intestine of man, rat, dog, rabbit, and cat, and the blood group B determinant in man and rabbit. Studies on the blood group active glycosphingolipids along the gastrointestinal tract of rat have revealed a complex distribution. The glandular cells of the stomach and epithelial cells of the large intestine express blood group B active glycosphingolipids. The cores of these are the ganglioseries, and the isogloboseries in the stomach and the lacto- (type 1) and neolactoseries (type 2) in the large intestine. The type 2 component is only expressed as a difucosyl and the type 1 as a monofucosyl compound. The epithelial cells of the small intestine are devoid of blood group B glycolipids, but express blood group H structures of which some has a branched core saccharide. One rat strain is lacking blood group A structures in the small intestine, but another is converting the H precursors to blood group A compounds. Both these strains always express blood group A structures in the large intestine. The expression of blood group A glycosphingolipids in the small intestine is inherited as a dominant trait.

Animals↗

Exudate variation in the rabbit gastrointestinal tract: a scanning electron microscope study.

The mucosal exudate from the gastrointestinal tract of six adult female New Zealand rabbits was studied using scanning electron microscopy and without any attempt being made to clean the luminal surface before screening. The exudate consisted of mucus, debris and bacteria. Qualitative assessment showed that the nature and distribution of exudate varied along the length of the gastrointestinal tract from the oesophagus to the anal canal, with little variation from animal to animal. Bacterial counts for rod-shaped bacteria were carried out on areas randomly selected from the upper, middle and lower oesophagus and the oesophageal-cardiac junction. The degree of bacterial colonisation was found to decrease along the length of the oesophagus from upper to lower parts, but it was increased at the oesophageal-cardiac junction. This assessment was not undertaken in the other regions of the gastrointestinal tract as the mucosal surface areas could not be easily measured owing to their undulating nature. The study indicates the variability of the mucosal exudate, which should be recognised as part of the true interface between ingested food and the cell surface along the gastrointestinal tract.

Animals↗

Complications of endoscopy of the upper gastrointestinal tract: a single-center experience.

OBJECTIVE: To evaluate prospectively the complications that occurred during consecutive endoscopies of the upper gastrointestinal tract. PATIENTS AND METHODS: We evaluated all endoscopies of the upper gastrointestinal tract (except endoscopic retrograde cholangiopancreatography and endosonography) performed at the Ambulatory Surgical Center at the Mayo Clinic in Jacksonville, Fla, between January 1999 and June 2002. A staff gastroenterologist with or without a trainee performed these procedures. Therapeutic procedures included esophageal band ligation, injection sclerotherapy, botulinum toxin injection, extended upper endoscopy, pneumatic balloon dilation, endoscopic mucosal resection, and endoscopic ablation using thermal laser, argon beam coagulator, or photodynamic therapy. All complications were tabulated prospectively as per mandatory state licensure reporting. RESULTS: Complications after diagnostic endoscopy of the upper gastrointestinal tract were related to anesthesia in 2 of the 12,841 patients. Perforations in 5 patients were associated with esophageal dilation (2), resection of duodenal lesions (2), or passage of a side-viewing instrument into the duodenum (1). No deaths occurred. CONCLUSIONS: Diagnostic endoscopy of the upper gastrointestinal tract is safe, with a complication rate of less than 1 per 5000 cases. Therapeutic endoscopy increases the risk of complications. Compared with complication rates published previously, our results from a single center indicate a favorable reduction in complications related to endoscopy of the upper gastrointestinal tract.

Aged↗

Inflammatory myofibroblastic tumors (inflammatory pseudotumors) of the gastrointestinal tract: how closely are they related to inflammatory fibroid polyps?

Inflammatory myofibroblastic tumors (inflammatory pseudotumors) and inflammatory fibroid polyps of the gastrointestinal tract both feature prominent inflammatory infiltrates admixed with spindle-shaped fibroblasts/myofibroblasts set in a collagenous, fibrovascular, or myxoid stroma. Erroneously, some have considered inflammatory fibroid polyps to be intraluminal manifestations of inflammatory myofibroblastic tumors. In this study, we have characterized the histopathology of inflammatory myofibroblastic tumors, tumors that have only rarely been reported in the gastrointestinal tract, and have focused on whether inflammatory myofibroblastic tumors and inflammatory fibroid polyps in the gastrointestinal tract are distinct or similar. Clinical, histopathologic, and immunohistochemical features of 38 inflammatory myofibroblastic tumors limited to the wall of the gastrointestinal tract were compared with those of 45 inflammatory fibroid polyps. Compared to patients with inflammatory fibroid polyps, those with inflammatory myofibroblastic tumors were younger (mean age 41 years vs. 53 years); had larger tumors (mean 8 +/- 5.2 cm vs. 3.6 +/- 4.6 cm); presented with abdominal pain, fever, and weight loss more frequently and less frequently had bowel obstruction. Inflammatory fibroid polyps had more eosinophils and fibrosis and fewer lymphoid cell infiltrates than inflammatory myofibroblastic tumors. A regular vascular pattern was a feature of inflammatory fibroid polyps but not of inflammatory myofibroblastic tumors. Most (82%) inflammatory fibroid polyps were positive for CD34 versus none of the inflammatory myofibroblastic tumors. Smooth muscle actin was more frequently positive in inflammatory myofibroblastic tumors than in inflammatory fibroid polyps (86% versus 13%). Inflammatory myofibroblastic tumors were much less frequent and were more evenly distributed in the gastrointestinal tract than inflammatory fibroid polyps. Both appear to be benign processes. Inflammatory myofibroblastic tumors, but not inflammatory fibroid polyps, had a tendency to recur. In conclusion, inflammatory myofibroblastic tumors of the gastrointestinal tract are extremely rare and differ clinically, histologically, and immunohistochemically from inflammatory fibroid polyps.

Actins↗

Transfer of functional immunoglobulin G (IgG) antibody into the gastrointestinal tract accounts for IgG clearance in calves.

The transfer of circulating immunoglobulin G1 (IgG1) antibody to the gastrointestinal tract in young calves was quantified by using bovine anti-dinitrophenol IgG1 antibody labeled with 125I. The antibody was administered to newborn calves by intravenous injection, and transfer of the labeled IgG1 to the gastrointestinal tract occurred as demonstrated by excretion of protein-bound label in the feces and by the presence of the labeled IgG1 antibody in the gastrointestinal tract lumen at necropsy. Sixty-eight percent of the [125I]IgG1 clearance occurred by transfer to the gastrointestinal tract. Protein-bound 125I in the gastrointestinal tract lumen retained 65% of the specific dinitrophenol-binding ability of the labeled antibody originally administered. These results show that (i) transfer to the intestinal lumen is the major means of IgG1 clearance in calves, and (ii) this transfer results in antigen-binding antibody in the intestinal tract lumen. The potential contribution to enteric immunity of IgG1 reaching the intestinal lumen from circulation remains to be determined.

Administration, Oral↗

Eosinophils in the gastrointestinal tract.

Although we know that eosinophils reside in the normal gastrointestinal tract and increase during inflammatory states, their exact role in gut homeostasis and in the pathogenesis of inflammatory processes is not certain. An increasing number of clinical reports suggest that eosinophils participate in the pathogenesis of mucosal inflammation, and emerging literature is beginning to define these mechanisms. For example, homing of eosinophils to the gastrointestinal tract is better understood with respect to the roles of specific eosinophilic attractants, such as the eotaxins and interleukin-5. As mechanisms of eosinophil recruitment, activation, and functional responses are further elucidated, novel targets for treatment strategies in specific diseases will likely follow. We review recent developments in eosinophil immunobiology as they relate to gastrointestinal inflammation and provide an update on clinical aspects of eosinophilic esophagitis as they relate to eosoinophilic diseases of the gastrointestinal tract.

Animals↗

Fundamental signals that regulate eosinophil homing to the gastrointestinal tract.

The histological identification of increased eosinophils in the gastrointestinal tract occurs in numerous clinical disorders; however, there is a limited understanding of the mechanisms regulating eosinophil trafficking into this mucosal surface. The results presented in this study characterize the processes regulating eosinophil homing into the gastrointestinal tract at baseline. Eosinophils were found to be present in the lamina propria of 19-day-old embryos and germ-free adult mice at concentrations comparable to those present in non-germ-free adult mice. Furthermore, eosinophil gastrointestinal levels were not altered by increasing circulating eosinophils after pulmonary allergen challenge. Gastrointestinal eosinophil levels were partially reduced in mice deficient in recombinase activating gene-1 (RAG-1), IL-5, or the beta common chain (betac), but these reductions paralleled reductions in circulating eosinophils. In contrast, mice deficient in eotaxin had a marked reduction in gastrointestinal eosinophils but normal levels of eosinophils in the hematopoietic compartments. Furthermore, eotaxin was important for regulating eosinophil levels, even in the presence of high levels of IL-5. These investigations demonstrate eosinophil homing into the gastrointestinal tract during embryonic development occurring independently of viable intestinal flora. Furthermore, eotaxin is identified as the primary regulator of eosinophil gastrointestinal homing under homeostatic states, and may therefore have a fundamental role in innate immune responses.

Allergens↗

[Zygomycetes in biopsies of the gastrointestinal tract].

Zygomycosis (Mucor- and Entomophtoramycosis) of the gastrointestinal tract is rare compared to other mycoses in the gastrointestinal area. The infection occurs mainly in immunosuppressed patients but rare cases concerning immunocompetent persons are also documented. Zygomycosis occurs in the gastrointestine primarily or due to disseminated disease. We report on a 48-year-old female alcohol-addicted patient who underwent gastric biopsies. The biopsy results showed invasive zygomycosis. Shortly thereafter, the patient died of sepsis. The second case presented here is a 15-year-old female patient with recurrent vomiting. Histological and immunohistochemical analysis of duodenal biopsy specimens revealed fungi of the class Zygomycetes. In addition, histological and/or microbiological examination demonstrated the presence of Candida in both cases.Zygomycosis of the gastrointestinal tract can have an aggressive course, making it important to know the morphological characteristics of the disease to facilitate early diagnosis and therapy. This is all the more important because the cultivation of fungi, as in our cases, is not always successful.

Biopsy↗

A review of the causes of upper gastrointestinal tract bleeding in children.

Bleeding may occur anywhere along the gastrointestinal tract, which covers a large surface area and is highly vascularized. While gastrointestinal bleeding is an alarming symptom for patients of any age, it can cause panic for children and their care givers. Early diagnosis and treatment of gastrointestinal bleeding may be essential. The differential diagnosis of bleeding from the upper gastrointestinal tract in infants and children includes numerous possibilities ranging from benign disorders which require little or no treatment at all, to serious diseases which require immediate intervention. This article reviews a variety of disorders which may cause upper gastrointestinal bleeding in infants and children. This is part one, of a two part series, on gastrointestinal bleeding in children. Part two will discuss bleeding from the lower gastrointestinal tract.

Child↗

Compliance changes of the gastrointestinal tract in streptozotocin-induced diabetic rats.

In order to elucidate diabetic gastrointestinal disorders, we measured the length, diameter, volume, and intraluminal pressure of the isolated segments of the duodenum, jejunum, ileum, and proximal colon during injection of Tyrode's solution into them, as well as wet weight. Wet weight of the stomach and of each intestinal segment of 3 cm length were similar between normal and diabetic preparations, except the duodenum. Wet weight of the diabetic duodenum was significantly heavier than that of normal. However, capacity of all diabetic gastrointestinal segments was significantly larger than that of normal ones, even after corrected for wet weight (ml/g wet weight). During saline injection, normal intestinal segments were more easily distended longitudinally than circumferentially. Contrarily, diabetic ones were distended more circumferentially than normal, as well as longitudinally. Pressure-volume relationships showed that pressure inside of the diabetic gastrointestinal tract increased much more moderately than that of normal one according to volume increase during saline injection. Similarly, tension inside of diabetic intestinal segments increased much more moderately than that of normal ones. Chord and slope compliance of diabetic gastrointestinal tract was generally larger than those of normal one. Histologically, there are no remarkable differences in cross-sectional area between normal and diabetic intestinal segments after usual fixation without intraluminal fixative injection. However, diabetic segments were much more remarkably dilated than normals were, when fixed after fixative injection. Greater compliance or distensibility of the diabetic gastrointestinal tract seemed to be one basic ground for dilatation, atony, larger appearance, transit delay, and motile disorders of the diabetic gastrointestinal tract.

Abdominal Muscles↗

Cost-effectiveness of misoprostol for prophylaxis against nonsteroidal anti-inflammatory drug-induced gastrointestinal tract bleeding.

Patients who take nonsteroidal anti-inflammatory drugs (NSAIDs) are at increased risk of upper gastrointestinal tract bleeding, which may be prevented with prophylactic prescription of misoprostol. Using data from the literature, we estimated rates of gastrointestinal tract bleeding in NSAID users, direct medical costs, years of life lost, and cost-effectiveness of a 1-year course of misoprostol in three clinical populations of NSAID users: all users, users aged 60 years or older, and users with rheumatoid arthritis. The incremental cost-effectiveness ratios for misoprostol as primary prevention were $667,400 per year of life saved for all NSAID users; $186,700 per year of life saved for users aged 60 years or older; and $95,600 per year of life saved for users with rheumatoid arthritis. Misoprostol as secondary prevention for those who continued to take NSAIDs despite having had an episode of gastrointestinal tract bleeding in the previous year was associated with incremental cost-effectiveness ratios less than $40,000 per year of life saved in all patient groups. We conclude that misoprostol is costly as primary prevention for NSAID-induced gastrointestinal tract bleeding in the groups examined but may be cost-effective as secondary prevention in patients with a proved history of gastrointestinal tract bleeding.

Aged↗

Impact of development of the gastrointestinal tract on infant feeding.

We have described the developmental pattern of the gastrointestinal tract under optimal conditions (i.e., low risk pregnancy and normal labor and delivery at term). The tissues do not develop simultaneously, and morphologic and functional development are not concurrent. An important consideration is the effect of suboptimal or even adverse conditions on the developmental sequence and attainment of maturity. Malnutrition during both the prenatal and postnatal periods may restrict the morphologic and biochemical development of the gastrointestinal tract. Dietary modifications have been shown to alter the developmental pattern of intestinal and pancreatic enzymes in animal models. Drugs and hormonal therapy given during pregnancy and early infancy have been known to cause developmental defects, but the specific effects on the gastrointestinal tract have not been evaluated. For further understanding of digestibility of nutrients and absorption in the perinatal period, these departures from the normal development of the gastrointestinal tract and the mechanisms by which these potential effects occur remain to be described. In view of these undetermined factors, in the case of intolerance or unavailability of milk from the natural mother, feedings should be individualized, with attention to direct measurement of enzyme concentrations, balance studies, or both, especially in the case of extreme prematurity or unusual requirements.

Dietary Carbohydrates↗