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[Comparison of conventional enteroclysis, intestinal ultrasound and MRI-enteroclysis for determining changes in the small intestine and complications in patients with Crohn's disease].

BACKGROUND: Enteroclysis, intestinal wall ultrasound (IWU) and abdominal magnetic resonance imaging (MRI) are three established methods in the diagnosis of Crohn's disease (CD). To date, however, the three methods have not been compared in one patient collective. AIMS: The present prospective study compared the relative performance of IWU, MRI and enteroclysis in determining the extent of disease involvement and intestinal complications in patients with CD both at initial diagnosis and during follow-up. PATIENTS AND METHODS: Included in the present study were 48 patients with confirmed CD (age: 19-66 years) examined with all three methods between August 1999 and December 2000. IWU was performed in B-mode with a 4-7 MHz convex transducer head and a 5-12 MHz linear transducer head by an experienced examiner. At MRI, T1 and T2 weighted sequenced (Flash 2D before and after intravenous application of gadolinium DTPA or TSE) were acquired in coronal and transverse planes. Enteroclysis was performed using conventional biphasic technique. Interpretation was conducted on the basis of a standardized catalogue of findings. RESULTS: Changes in bowel segments consistent with inflammation were identified in 41 of 48 patients. All three methods returned equivalent findings with regard to the length of inflamed bowel segments (IWU, range: 3-25 cm, mean: 12 cm; MRI, range: 3-25 cm, mean: 10 cm; enteroclysis, range: 3-30 cm, mean: 11 cm) and wall thickness (IWU, range: 4-10 mm, mean: 7 mm; MRI, range: 5-10 mm, mean: 7 mm; of nine patients with stenotic change, five were correctly diagnosed with IWU (sensitivity, 55.6%; specificity, 97.4%), four with MRI (sensitivity, 44.4%; specificity, 100%) and six with enteroclysis (sensitivity, 66.7%; specificity, 100%). Fistulae were correctly identified in five patients with IWU (sensitivity, 55.6%; specificity, 97.4%), in four with MRI (sensitivity, 44.4%; specificity, 100%) and in six with enteroclysis (sensitivity, 66.7%; specificity, 100 %) of a total of nine patients with confirmed fistula formation. Abscesses were correctly identified in five patients with IWU (specificity, 66.7%; specificity, 100%), in five with MRI (sensitivity, 83.3%; specificity, 100%) and in no patients with enteroclysis (sensitivity, 0%; specificity, 100%) in six patients with abscesses. CONCLUSION: Both IWU and MRI identify extent, severity and intestinal complications with adequate diagnostic accuracy in patients with CD. Both techniques possess the potential for replacing enteroclysis in the work-up of CD. Enteroclysis should be reserved for the work-up of complex fistula systems.

Adult↗

Evidence for a role of the gut hormone PYY in the regulation of intestinal fatty acid-binding protein transcripts in differentiated subpopulations of intestinal epithelial cell hybrids.

Peptide tyrosine tyrosine (PYY) is a gut hormone present in endocrine cells in the lower intestine that can be released by the presence of luminal free fatty acids (FFAs). The biological action of this peptide includes inhibition of gut motility and gastrointestinal and pancreatic secretions. Intestinal fatty acid-binding protein (I-FABP) binds FFA and may be involved in their cytosolic trafficking. Quantitative in situ hybridization on heterogeneous populations of small intestinal somatic cell hybrids selected for endogenous I-FABP expression (hBRIE 380i cells) demonstrated a 5-fold increase in I-FABP transcripts in response to PYY (within 6 h) that was confined to clusters of differentiated cells, whereas ribonuclease protection assays performed on heterogeneous populations of these cells showed no significant differences. High affinity PYY receptors, with an IC50 of 5-50 pM, were identified in both differentiated and nondifferentiated cell populations, as determined by competitive binding assays and autoradiography. In situ hybridization of rat ileal tissue also revealed differing patterns of mRNA expression for liver fatty acid-binding protein (L-FABP) and I-FABP. Only I-FABP mRNA was detected in the villus tips. This localization correlated with the expression pattern of I-FABP mRNA in the hBRIE 380i cells where changes in transcripts were observed only in differentiated cells that did not incorporate bromodeoxyuridine. The sustained expression of I-FABP transcripts in the villar tips suggests (unlike L-FABP) that older terminally differentiated cell populations of the mucosa can still be PYY responsive. These studies demonstrate that physiological concentrations of PYY can regulate I-FABP and place this peptide in a key position as part of a feedback system that determines the processing of cytosolic FFA in the enterocyte. In addition, these studies suggest a mechanism whereby luminal agents can modulate expression of proteins in terminally differentiated cells in the gastrointestinal mucosa.

Animals↗

[Nitrogen and amino acid resorption in the small intestine of growing swine. 1. Animal study method, nitrogen content and amino acid composition of the small intestine chyme by administration of various proteins].

The amount of endogenous N in the chyme at the end of the small intestine and the amino acid composition of the ileum chyme were ascertained with growing pigs with ileorectostomy after feeding qualitatively differentiated protein sources. In dependence on the protein used, distinct differences turned out for some amino acids with regard to their content in the ileum chyme. Bacteriologic and histologic investigations subsequent to the dissection of the test animals showed that - in comparison to the control animals-the functions of the small intestine remained the same during the time of the experiment. The experiment method described appears to be suitable for absorption investigations up to the end of the small intestine of growing pigs.

Amino Acids↗

Intestinal first-pass metabolism of nitrosamines. 2. Metabolism of N-nitrosodibutylamine in isolated perfused rat small intestinal segments.

In a previous study a high first-pass metabolism of N-nitro-sodi-[1-14C]butylamine (NDBA, 0.32-730 microM) has been shown in isolated perfused rat small intestinal segments. In the present work the identification and quantitation of metabolites in samples of perfusate and absorbed fluid (absorbate) is reported. After HPLC enrichment and purification five metabolites could be identified by GLC-MS: N-nitrosobutyl-(3-hydroxybutyl)amine (NB3HBA), N-nitrosobutyl-(4-hydroxybutyl)amine (NB4HBA), N-nitrosobutyl-(3-carboxypropyl)amine (NB3CPA), N-nitrosobutyl-(2-hydroxy-3-carboxypropyl)amine (NB2H3CPA) and N-nitrosobutylcarboxymethylamine (NBCMA), representing greater than 95% of total metabolites. omega-hydroxylation leading to NB4HBA and NB3CPA accounted for 75-95% of total metabolites. The formation of their follow-up products NB2H3CPA and NBCMA was too small for quantitative analysis. In absorbate NB3CPA was by far the most important metabolite. The hydroxylation of NB4HBA to NB3CPA was more efficient in jejunal as compared to ileal segments. omega-1-hydroxylation to NB3HBA and, as reported previously, alpha-hydroxylation were only minor metabolic pathways. In conclusion, a high first-pass metabolism of NDBA to the proximate bladder carcinogen NB3CPA takes place during its absorption in rat small intestine. This is in contrast to the observation in rat liver preparations, where alpha- and omega-1-hydroxylation are the predominant pathways. The intestinal first-pass metabolism may play a key role explaining the increased incidence of bladder tumors in rats after low oral doses of NDBA.

Animals↗

Changes in the intestinal lactase activity in the small intestine of two breeds of swine from birth to 6 weeks of age.

Total and specific lactase activities in the small intestine of Chester White and Hampshire pigs were measured at 1, 8, 15, 22, 29, and 43 days of age. The small intestine was divided into 10 segments of equal length, the proximal 10 cm of each segment was scraped, and the scrapings were homogenized for use in the lactase determinations. Significant breed, age, and segment differences were observed for both specific and total activities. In both breeds, the total lactase activity at 1 day of age was lower than that at any other age. After reaching maximal levels at 15 days of age, the total activity declined with the loss of activity occurring primarily in the ileum. At 1 and 8 days of age, the total lactase activities for the two breeds were similar, but the Chester White pigs had higher activities at all other ages. The pattern of changes in specific activity with age was similar for both breeds. The mean specific activity was highest at 1 and 8 days of age and then fell progressively to minimal levels at 43 days of age. Chester Whites had higher specific activities than Hampshires during the first 4 weeks of life, but at 6 weeks of age there was little difference between the breeds. The peak lactase activity, expressed as total or specific activity, occurred in the proximal one-third of the small intestine of both breeds, and the distal one-third of the gut had relatively low activities as the animals matured.

Age Factors↗

Expression of cysteine-rich intestinal protein in rat intestine and transfected cells is not zinc dependent.

The cysteine-rich intestinal protein (CRIP) is a member of a superfamily of proteins containing the LIM motif (a double zinc finger) that has been shown to bind zinc. The role of zinc in the regulation of CRIP was examined in adult rats, cultured intestinal epithelial cells and in a transient transfection system. When adult male rats were fed diets with various amounts of zinc, the amount of ileal CRIP mRNA was only 19% lower in rats fed a zinc-deficient diet (1 mg Zn/kg) and was not different in the zinc-supplemented group (180 mg Zn/kg) compared with the zinc-adequate group (30 mg Zn/kg). In contrast, metallothionein mRNA levels were 76% lower and 80% greater than control levels in the zinc-deficient and zinc-supplemented groups, respectively. Using the chloramphenicol acetyltransferase (CAT) reporter gene, 5'-deletion products of the CRIP genomic promoter were tested for basal and zinc-induced CAT activity in transiently transfected IEC-6 cells. Treatment of the cells with zinc did not alter CAT activity of any construct. These results suggest that CRIP is not directly regulated by zinc in the intestine of rats.

Analysis of Variance↗

A gene encoding an intestinal-enriched member of the Krüppel-like factor family expressed in intestinal epithelial cells.

The Krüppel-like factors make up a multigene family of transcription factors that have discrete patterns of expression, implying they play important biological roles in the tissues in which they are expressed. We have identified and characterized the cDNA for a novel murine transcription factor that is an additional member of the Krüppel-like family of transcription factors, named intestinal-enriched Krüppel-like factor (IKLF). This gene appears to be a homolog of the human BTEB-2 gene, although it exhibits a different pattern of tissue expression and the translated product is larger. IKLF is expressed in a limited number of tissues; the highest levels of IKLF expression are found in the digestive tract. IKLF shows temporal changes in expression during embryogenesis indicating that this gene is developmentally regulated. In addition, IKLF expression is limited to the epithelial lining of the intestine and is localized primarily to the base of the crypts in the adult intestine. The IKLF cDNA encodes for a 446 amino acid protein and is able to transactivate by binding specific DNA elements that are also recognized by other members of the Krüppel-like family. In addition, mutations in the activation domain attenuate the ability of this protein to function as a transcription factor. Collectively, these findings show that we have identified a transcription factor that is expressed predominantly in the epithelial crypt cells of the gastrointestinal tract and is a member of the Krüppel-like family of transcription factors.

Amino Acid Sequence↗

Changes in ornithine metabolic enzymes induced by dietary protein in small intestine and liver: intestine-liver relationship in ornithine supply to liver.

Compared with the activity obtained with a high-protein diet in rats, a low-protein diet doubled the activity of ornithine aminotransferase [EC 2.6.1.13] (OAT), a key enzyme for citrulline synthesis, in the small intestine. The induction of ornithine aminotransferase in the small intestine by the low-protein diet and its suppression by the high-protein diet, and the converse in the liver, were immunohistochemically verified with anti-OAT antiserum. The immunohistochemical studies revealed that ornithine aminotransferase molecules localized in the villous surface epithelia, but not in the cryptic epithelia, were most responsive to the changes in dietary conditions, these results indicating that intestinal ornithine aminotransferase may be involved in the ornithine supply to the liver, with the reversal of the enzyme reaction occurring with a low-protein diet. Reconstituted model experiments on citrulline synthesis revealed that the addition of ornithine carbamoyl-transferase and carbamoyl phosphate was essential to overcome the unfavorable equilibrium of the reverse reaction, and the further addition of glutamate dehydrogenase and ammonia resulted in a stimulating effect.

Animals↗

The endoscopic appearance of severe intestinal Mycobacterium avium complex infection as a coarsely granular mucosa due to massive infiltration and expansion of intestinal villi without mucosal exudation.

Although Mycobacterium avium complex (MAC) is the most common opportunistic pathogen at postmortem in patients with AIDS, many cases are not recognized premortem. A patient with advanced AIDS had diarrhea, fecal occult blood, and iron deficiency anemia. Esophagogastroduodenoscopy showed an extensive coarsely granular mucosa, resistant to endoscopic irrigation and brushing, in the descending duodenum. Histologic analysis of duodenal biopsies confirmed expansion of intestinal villi due to massive villar infiltration by acid-fast bacilli and no mucosal exudation. An absence of mucosal exudation is consistent with an attenuated local immunologic response in advanced AIDS. MAC was isolated from mycobacterial culture of duodenal biopsies. The currently reported endoscopic appearance of intestinal MAC can aid in diagnosis by alerting the endoscopist to send biopsies for mycobacterial stains and cultures when MAC infection is suggested by this endoscopic appearance. However, even in the absence of endoscopically evident lesions, gastrointestinal endoscopic biopsy is appropriate to exclude occult opportunistic pathogens in an AIDS patient with wasting or significant gastrointestinal complaints. The currently reported pathologic findings show that villar engorgement and hypertrophy is a sufficient explanation for the granular endoscopic appearance of intestinal MAC and that mucosal exudation is not required to produce this appearance.

AIDS-Related Opportunistic Infections↗

Migration of wire mesh into the intestinal lumen causing an intestinal obstruction 30 years after repair of a ventral hernia.

Wire mesh repair of abdominal wall hernias was abandoned almost four decades ago. Recently, a woman who had a wire mesh repair of an incisional hernia in 1964 came to the emergency room with a complete small bowel obstruction. The obstruction was caused by a segment of wire mesh that broke off from the abdominal wall and migrated into the small bowel lumen. During the preceding 2 years, she had been evaluated by two different gastroenterologists for chronic anemia, but they failed to obtain an evaluation of the small intestine. This case report shows that abdominal foreign bodies may migrate into the intestinal tract. I recommend that an evaluation of chronic anemia in the geriatric patient include evaluation of the small intestine.

Cesarean Section↗

Molecular aspects of intestinal epithelial cell-bacterial interactions that determine the development of intestinal inflammation.

The mechanisms by which intestinal epithelial cells perceive and respond to microbes, both pathogenic and commensal, is important to understand the pathogenesis of inflammatory diseases. Recent work has established that most eukaryotic cells possess families of receptors that can detect the structural signatures of prokaryotic life. Cells respond to the detection of microbes by activation of distinct cytoplasmic signaling cascades that ultimately result in the transcriptional activation of programs of genes with proinflammatory and anti-apoptotic function. These responses generally suffice to eliminate microbial threats. Also important are potential mechanisms by which microbes can influence the intestinal epithelial responses, influences with significant implications for the normal function of the intestine and inflammatory diseases.

Bacteria↗

Replication of M-tropic HIV-1 in activated human intestinal lamina propria lymphocytes is the main reason for increased virus load in the intestinal mucosa.

The gastrointestinal tract is the site of early abundant HIV replication and associated marked CD4 T-cell depletion. The aim of this study was to characterize the basis for the increased HIV replication in this compartment. Isolated mononuclear cells of the peripheral blood (PBMCs), the intestinal lamina propria (LPMCs), and purified gut lamina propria CD4 T-cell subpopulations (LP T cells) were isolated, phenotypically characterized, and infected in vitro with 2 different HIV-1 strains. T-cell subpopulations were analyzed by fluorescence-activated cell sorter. HIV-1 core protein p24 was determined in supernatants after in vitro infection. Furthermore the effect of T-cell stimulation on the replication of M- and T-tropic HIV strains was studied. In vitro replication of HIV-1 was significantly increased in CD69 compared with CD69 CD4 LP T cells, while there was no difference between CD103 and CD103 CD4 LP T cells. Experimental stimulation of LPMCs, which mimics activation by intestinal pathogens frequently present in the bowel of HIV-infected patients, further dramatically enhances HIV replication (24.5-fold) compared with nonstimulated LPMCs. M-tropic HIV-1 showed a preferential replication in LPMCs, while T-tropic HIV-1 strain showed a preferential replication in PBMCs. Thus, the elevated activation state of target cells in the intestine and not the expression of the homing marker CD103 is directly linked to massive HIV production.

Antigens, CD↗

Role of the Yersinia outer membrane protein YadA in adhesion to rabbit intestinal tissue and rabbit intestinal brush border membrane vesicles.

The Yersinia virulence plasmid confers on strains of Yersinia pseudotuberculosis and Y. enterocolitica an adhesive potential superior to the one encoded by the chromosome alone. We have evaluated the role of the plasmid-encoded outer membrane protein YadA (formerly called Yopl) in adhesion. Insertional inactivation of the yadA gene (formerly called yopA), which encodes YadA, led to a reduction in the capacity of plasmid-carrying strains of Y. pseudotuberculosis 0:III and Y. enterocolitica 0:9 to adhere to intestinal tissue, brush border membranes and polystyrene surfaces. The adhesive characteristics of the mutants were comparable to those of their plasmid-cured counterparts. When the yadA gene from Y. pseudotuberculosis serotype 0:III or Y. enterocolitica serotype 0:3 or 0:8 was cloned into an Escherichia coli strain, increased ability to adhere to intestinal tissue, brush border membrane vesicles and polystyrene was transferred concomitantly. The introduction of the yadA gene from Y. pestis, which is unable to express YadA due to a one base pair deletion, did not change the adhesive characteristics of E. coli. Expression of YadA in the outer membrane may, therefore, make an important contribution to intestinal adherence of the two enteropathogenic members of the Yersinia species, Y. pseudotuberculosis and Y. enterocolitica.

Animals↗

Intestinal fluid transport in the small intestine of normotensive and spontaneously hypertensive rats: the importance of enteric nerves, chloride and bicarbonate secretion.

Fluid transport was studied in periarterially denervated jejunal segments of spontaneously hypertensive rats (SHR) of the Okamoto strain and as a control also in Wistar-Kyoto rats (WKR). In agreement with the findings of an earlier report a 'spontaneous' fluid secretion was observed in SHR whereas the intestinal segments of WKR absorbed fluid. The fluid secretion in SHR was inhibited by tetrodotoxin or lidocaine placed on the serosal surface of the intestinal segment under study. These observations confirm our earlier proposal that secretory nervous pathways in the enteric nervous system evoke the fluid secretion in SHR. In an attempt to analyse the cellular mechanisms that underlie the fluid secretion in SHR the animals were given loop diuretics in doses that evoked diuresis. No effect on intestinal fluid transport was seen in SHR or WKR. Furthermore, to study the importance of bicarbonate transport alkaline secretion was monitored with a pH-stat technique. In the initial part of the experiments the alkaline secretion in SHR and WKR was similar. In half of the SHR experiments alkaline secretion increased with time. This increase could be completely reversed with hexamethonium and atropine (only tested in three experiments). The time course of the alkaline and fluid secretion in SHR did not coincide, indicating that bicarbonate ion transport was not the major cause of fluid secretion in SHR. In agreement with this conclusion it was observed that acetazolamide (a blocker of carbonic anhydrase) did not influence rate of fluid transport in SHR or WKR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Somatostatin and its analogue (D-Trp8,D-Cys14)-somatostatin do not modify intestinal absorption in vivo of carbohydrates in hamster intestine, but they do modify some disaccharidases.

Somatostatin is a widely distributed hormone localized in the central nervous system, pancreas and gastrointestinal tract. We have investigated the possible influence of somatostatin and a synthetic analogue, (D-Trp8,D-Cys14)-somatostatin, on the intestinal absorption 'in vivo' of D(+)-glucose and D(+)-galactose and also the effect on disaccharidase intestinal activities in hamster. Somatostatin, or its analogue, (12 micrograms/100 g body wt) was administered intraperitoneally 4 or 14 h prior to experiments. The results are compared to control animals. Animals treated with somatostatin and the synthetic analogue showed that there were no significant difference from control animals with respect to intestinal absorption of carbohydrates. Somatostatin produced inhibition of brush-border lactase activity in females only, whereas brush-border sucrase was increased 14 h after treatment in males and females, and brush-border maltase was inhibited in females only 4 h after hormone administration.

Animals↗

Impaired defense of intestinal mucosa in mice lacking intestinal trefoil factor.

The mechanisms that maintain the epithelial integrity of the gastrointestinal tract remain largely undefined. The gene encoding intestinal trefoil factor (ITF), a protein secreted throughout the small intestine and colon, was rendered nonfunctional in mice by targeted disruption. Mice lacking ITF had impaired mucosal healing and died from extensive colitis after oral administration of dextran sulfate sodium, an agent that causes mild epithelial injury in wild-type mice. ITF-deficient mice manifested poor epithelial regeneration after injury. These findings reveal a central role for ITF in the maintenance and repair of the intestinal mucosa.

Animals↗

Release of vasoactive intestinal polypeptide from the cat small intestine exposed to cholera toxin.

During a four hour observation period vasoactive intestinal polypeptide (VIP) is released in increasing amounts from the feline small intestine exposed to cholera toxin. As VIP is known to be located almost exclusively in the intestinal nerves, the present findings strongly suggest that cholera toxin activates the enteric nervous system. The findings of this and other studies performed in this laboratory lead to the proposal that the choleraic secretion is, at least in part, secondary to the activation of intramural nervous reflexes in the gut.

Animals↗

Effect of intravenous ranitidine and omeprazole on intestinal absorption of water, sodium, and macronutrients in patients with intestinal resection.

BACKGROUND: H2 receptor blockers and proton pump inhibitors reduce intestinal output in patients with short bowel syndrome. AIMS: To evaluate the effect of intravenous omeprazole and ranitidine on water, electrolyte, macronutrient, and energy absorption in patients with intestinal resection. METHODS: Thirteen patients with a faecal weight above 1.5 kg/day (range 1.7-5.7 kg/day and a median small bowel length of 100 cm were studied. Omeprazole 40 mg twice daily or ranitidine 150 mg twice daily were administered for five days in a randomised, double blind, crossover design followed by a three day control period with no treatment. Two patients with a segment of colon in continuation were excluded from analysis which, however, had no influence on the results. RESULTS: Omeprazole increased median intestinal wet weight absorption compared with no treatment and ranitidine (p<0.03). The effect of ranitidine was not significant. Four patients with faecal volumes below 2.6 kg/day did not respond to omeprazole; in two absorption increased by 0.5-1 kg/day; and in five absorption increased by 1-2 kg/day. Absorption of sodium, calcium, magnesium, nitrogen, carbohydrate, fat, and total energy was unchanged. Four high responders continued on omeprazole for 12-15 months, but none could be weaned from parenteral nutrition. CONCLUSION: Omeprazole increased water absorption in patients with faecal output above 2.50 kg/day. The effect varied significantly and was greater in patients with a high output, but did not allow parenteral nutrition to be discontinued. Absorption of energy, macronutrients, electrolytes, and divalent cations was not improved. The effect of ranitidine was not significant, possibly because the dose was too low.

Adult↗