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Bacterial colonization and infection in the neonate.

The vast majority of healthy term neonates tolerate their abrupt introduction to the bacterial world with little risk of infection. However, infants who require a longer hospital stay are at greater risk of having an infection, particularly when intensive care is needed. In one study, 15.3 percent of the infants in an intensive care unit acquired a nosocomial infection. Gram-negative bacilli have emerged as the principle cause of nosocomial infection. Nosocomial infection due to gram-negative bacilli usually occurs in neonates already colonized with gram-negative bacilli in the pharynx or intestine, and the risk of colonization with hospital strains of gram-negative bacilli (which are often resistant to multiple antibiotics) increases dramatically the longer a baby stays in intensive care. The factors which predispose individual neonates to colonization and infection with gram-negative bacilli require further study, but gram-negative bacilli are most often transmitted among neonates on the hands of personnel. Neonates in whom intestinal colonization with gram-negative bacilli develops are a particularly important reservoir of gram-negative bacilli in the nursery; once colonized, infants may harbour antibiotic-resistant hospital strains of gram-negative bacilli in their stool for more than a year. Pharyngeal colonization with alpha streptococci appears to protect neonates from pharyngeal colonization with gram-negative bacilli, and bacterial interference may play an important role in regulating intestinal colonization as well. Investigation of the mechanisms of bacterial interference may lead to better understanding of the colonization process and development of alternatives to classic infection control methods.

Bacteria↗

[A study of the evacuatory function of the small and large intestines using the dynamic scintigraphic method in inflammatory diseases of the intestines].

Intestinal and colon evacuatory function was studied in 10 patients without pathology of the digestive organs and in 66 patients with chronic colitis. This method allows adequate assessment of the state of the hepatobiliary system, intestinal and colon evacuatory function without additional radiation exposure of the examinees and personnel.

Adult↗

European Cooperative Crohn's Disease Study (ECCDS): clinical features and natural history.

In the European Cooperative Crohn's Disease Study patients from 14 centers were included in whom diagnosis was made within 2 years before study entry on the basis of generally accepted radiological, endoscopical and/or histological criteria or a combination of all. Reasons for exclusion were: diagnosis older than 2 years in patients who did not require active treatment, age less than 18 years, duration of symptoms less than 3 months, presence of complications which potentially required emergency surgery. Data on clinical features were obtained in 633 patients, of whom 452 were eligible to participate in the study. In 110 patients randomized to placebo the natural course of Crohn's disease was studied. Patients with ileocolonic involvement were younger than patients with either colonic or small intestinal involvement only. Classic ileitis terminalis was present in 14% of the patients. 49% of the patients had combined involvement of both the small and large intestine. 30% of patients had only small intestinal involvement, and in 21% colonic disease was present. Small intestinal involvement was associated with a significantly lower Crohn's Disease Activity Index (CDAI) than other anatomical locations of the disease. Perianal disease was more often associated with colonic than with small intestinal involvement. 60% of placebo patients with active disease at entry achieved at least a transient remission within the initial 5 months of study. After 2 years, 23% of patients with active disease at entry and 68% of patients with quiescent disease had reached or maintained a remission, respectively. By stepwise multiple linear regression analysis long duration of disease between diagnosis and randomization, normal serum albumin and combined involvement of small intestine and colon were identified as predictors of a more favorable outcome of patients treated with placebo. In contrast, extensive small bowel disease, treatment with steroids and bowel resection prior to study entry correlated with a less favorable outcome. However, by life table analysis outcome of previously untreated and treated patients in the placebo group was similar.

Adrenal Cortex Hormones↗

Perifollicular fibromatosis cutis with polyps of the colon--a cutaneo-intestinal syndrome sui generis.

In the present study, a peculiar fibromatosis cutis in two siblings has been reported the dermatosis being characterized by innumerable perifollicular fibromas on face, neck and trunk as well as multiple fibromata pendulantia. Since the father allegedly had skin lesions resembling those of his two affected children, an inherited condition is assumed for the disease manifesting itself rather late in age. In the female patient, several adenomatous colon polyps one being transformed into carcinoma were found. Since the association of distinct epithelial and mesenchymal tumours of the skin and the cranial bones with multiple colon polyps is typical for Gardner's syndrome, we have discussed in detail the possiblity of an unknown variant of it. On the other hand, most features of Gardner's syndrome (cutaneous and subcutaneous epidermoid cysts, desmoid tumours, generalized osteomas, a marked multitude of colon polyps, early manifestation of skin and bone changes) were absent in both cases whereas, to our knowledge, in Gardner's syndrome perifollicular fibromas have never been seen. Since perifollicular fibromas are organoid tumours of the mesenchymal hair sheath being clearly defined both clinically and histologically, they must not be confused with the equally well characterized cutaneous tumours of Gardner's syndrome. We are prone to assume that the (irregular?) ASSOCAITION OF MULTIPLE PERIFOLLICULAR FIBROMAS AND COLON POLYPS Represents a distinct nosological entity neither identical with Gardner's syndrome nor with any other known dermo-intestinal syndrome. Thus, perifollicular fibromatosis should alert the dermatologist to consider periodic thorough examination for intestinal polyps the more as they may change into malignant growth.

Adult↗

Effect of oxidants on small intestinal brush border membranes and colonic apical membranes--a comparative study.

This study compares composition of the rat small intestinal brush border membranes (BBM) and colonic apical membranes (CAM) and their susceptibility to in vitro exposure to various oxidants. Differences were observed between BBM and CAM in their lipid composition, sugar content, alkaline phosphatase (ALP) activity and cholesterol/phospholipid ratio. BBM and CAM were exposed to superoxide generated by xanthine+xanthine oxidase (X-XO) or peroxides such as tertiary butyl hydroperoxide (tBuOOH) and hydrogen peroxide (H(2)O(2)) and alterations in ALP activity, peroxidation parameters and membrane lipids were analyzed. Exposure of BBM and CAM to superoxide resulted in decrease in ALP activity and increase in peroxidation parameters such as protein carbonyl content, malondialdehyde and conjugated diene. Superoxide exposure also resulted in lipid alterations specifically in certain phospholipids. These alterations were prevented either by superoxide dismutase or by allopurinol. Peroxides did not have any significant effect. These results suggest that both BBM and CAM are susceptible to superoxide, which can bring about peroxidation and degradation of membrane lipids specifically, certain phospholipids.

Alkaline Phosphatase↗

Colonic mucosal replacement by syngeneic small intestinal stem cell transplantation.

A novel method of colonic mucosal replacement by transplantation of disaggregated small intestinal epithelium is described. Thirty-one inbred rats had the ascending colon isolated, and surgical mucosectomy was performed on the "free" loop. Epithelial cell aggregates were isolated from postnatal small intestine using collagenase and dispase digestion, then 20 microL of the cell suspension was "seeded" over the denuded colonic muscle of 25 recipient rats. Six control rats had surgical mucosectomy only. All loops were retrieved after 14 days for histologic examination. Stem cell lineage studies were used with selective staining protocols to identify enterocytes, goblet cells, entero-endocrine cells, and Paneth cells. A neomucosa with typical small bowel morphology including crypts and villi and all four stem cell lineages was regenerated by transplanted cells on the colonic muscle in 19 of 25 (76%) recipients. Control loops showed no epithelial regrowth confirming total mucosectomy. With appropriate stromal support, transplanted small intestinal stem cells have the capacity to re-epithelialize denuded colonic muscle with small bowel neomucosa.

Animals↗

Laboratory identification and enteropathogenicity testing of Serpulina pilosicoli associated with porcine colonic spirochetosis.

Pathogenic intestinal spirochetes of swine include Serpulina hyodysenteriae, a strongly beta-hemolytic spirochete that causes swine dysentery, and S. pilosicoli, a weakly beta-hemolytic intestinal spirochete (WBHIS) that causes porcine colonic spirochetosis. Because of the existence of nonpathogenic WBHIS in the normal swine colon, it is important to develop laboratory procedures for accurate identification of S. pilosicoli. The purpose of the present study was to assess hippurate hydrolysis and polymerase chain reaction (PCR) amplification of specific 16S ribosomal RNA (rRNA) sequences for identification of porcine S. pilosicoli. Additionally, the enteropathogenicity of 8 field isolates of porcine S. pilosicoli was determined by challenge exposure of 1-day-old chicks and sequential histologic examination of the cecal mucosa. The field isolates of porcine S. pilosicoli hydrolyzed hippurate and yielded S. pilosicoli-specific products by PCR amplification of 16S rRNA sequences. Although all of the field isolates of porcine S. pilosicoli attached to the cecal epithelium of challenge-exposed chicks by day 21 postinoculation, some isolates had locally invasive phenotypes. We concluded that identification of porcine S. pilosicoli could be made on the basis of results of hippurate hydrolysis and 16S rRNA PCR amplification. Challenge inoculation of 1-day-old chicks followed by histologic examination of the cecal mucosa demonstrated the enteropathogenicity of porcine S. pilosicoli.

Animals↗

Transepithelial transport of large particles in rat: a new model for the quantitative study of particle uptake.

The transport of large particles across the intestinal mucosa and the mechanisms of transfer of the particles into the body are still little understood. Fluorescent polystyrene latex particles (2 microm diam.) were administered orally to young male Sprague-Dawley rats in doses of 2.33 x 10(3), 2.33 x 10(6) and 2.33 x 10(9) particles. After 60 min, Peyer's patches and Peyer's patch-free tissues were collected from the small intestine and colon. A novel technique was used to exclude non-translocated particles adherent to the mucosal surface; the intestinal epithelium was stripped from the intestine by immersion in Hanks' balanced salt solution containing 1.5 mM EDTA. Particles in solubilized samples of intact and epithelium-stripped Peyer's patches and Peyer's patch-free intestinal tissue and colon were quantified by fluorescence microscopy. The location of particles within the intact and epithelium-stripped gut samples was revealed by confocal microscopy. Particles were shown to have been taken up along the entire length of the small and large intestines via both Peyer's patches and the normal intestinal epithelium. The number of particles detected in the distal region was greater than in the proximal part of the small intestine, although the difference was not statistically significant. This study has revealed that large numbers of non-translocated particles adhered to the mucosal surface resulting in a high background count. The assay system was considerably improved by the epithelium-stripping technique. The process of transepithelial uptake is a potentially important route of uptake of toxic, immunologically active and radioactive substances. These particles are much larger than the conventionally accepted upper limit for absorbed materials.

Administration, Oral↗

Effects of bromocriptine on the heart and the peripheral circulation of anesthetized cats.

Dopaminergic stimulants such as bromocriptine have multiple effects on the circulation. Based on dose-response curves obtained in preliminary experiments, we compared the effects of 30 micrograms/kg bromocriptine and 0.4 mg/kg dihydralazine infused intravenously over a period of 10 min into seven chloralose-urethane-anesthetized cats each. A third group of cats received placebo solution. The effect of both drugs on blood pressure was comparable, but other systemic hemodynamic variables and regional blood flows, measured with tracer microspheres, were altered differently. Bromocriptine lowered heart rate, did not change cardiac output, and increased total peripheral conductance modestly, whereas dihydralazine produced marked increases in cardiac output and total peripheral conductance. Bromocriptine dilated the vascular beds of the brain, kidneys, adrenal glands, and skeletal muscle without increasing flow through most of them. Dihydralazine caused striking vasodilation in the heart, brain, small intestine, and colon and a modest increase in conductance in the kidneys, adrenal glands, and skeletal muscle. Flow through the heart, brain, small intestine, and colon was increased. Vasoconstriction was observed in the pancreas with bromocriptine and in the liver, spleen, and, to a small extent, pancreas with dihydralazine. The distribution of effects was somewhat similar to the effects of dihydropyridine-derived calcium antagonists. With dihydralazine the fall in blood pressure was caused by peripheral vasodilation only, whereas with bromocriptine both peripheral vasodilation and effects on the heart contributed to the fall in blood pressure.

Anesthesia, General↗

Mitochondrial gene expression in the human gastrointestinal tract.

In the human gastrointestinal epithelium, in situ hybridisation demonstrates that 12 S and 16 S mitochondrial ribosomal RNAs show maximal steady-state levels on the surface epithelial cells of the normal small intestine and colon. The mitochondrial mRNAs, cytochrome b and NADH dehydrogenase (IV) have a uniform distribution throughout the crypt and surface (villus) epithelial cells of the small intestine and colon. Histochemical stains for the activity of the mitochondrial respiratory chain enzymes succinate dehydrogenase and cytochrome oxidase also show almost uniform activities throughout the crypt-surface epithelial cell axis in the small and large intestines. In sections of normal human oesophagus the levels of mitochondrial ribosomal RNAs, mitochondrial mRNAs and the activities of mitochondrial respiratory chain enzymes are maximal over the basal cells of the stratified squamous epithelium. These results show a relative increase in mitochondrial ribosomal RNA expression compared with mitochondrial mRNAs in surface cells of simple intestinal epithelia.

DNA Probes↗

Cell kinetics analysis of background colonic mucosa of patients with intestinal neoplasms by ex vivo autoradiography.

Studies of the cell kinetics of the colonic crypts could explain the morphogenesis of colonic adenomas and results suggest that a derangement of the proliferative zone of the colonic crypts takes place before adenoma development. This study was conducted to determine whether this is the case or not. The labelling distribution and labelling index (LI) of the colonic crypts was examined with ex vivo autoradiography. Eight patients with intestinal neoplasms, three with familial polyposis coli, four with ordinary colon cancer, and one with two colonic adenomas. Similar labelling distributions and absent upward shift of the active proliferative zone in crypts were observed in patients with familial polyposis and in those with non-polyposis cancer, or adenomas. The non-proliferative zone of the crypts was well preserved in all eight patients. The mean of the labelling index of the three patients with familial polyposis coli was 8.35% (3.17), values expressed as means (SD) and that of the five patients with non-polyposis cancer, or adenomas was 8.55% (3.20). None of the eight patients showed derangement of the proliferative zone of colonic crypts. This result is compatible with the hypothesis that adenomas are detected first as 'buds of adenomas', which sprout into the lamina propria mucosae in the middle part of normal crypts.

Adenocarcinoma↗

Surgical therapy for the short bowel syndrome.

The introduction of total parenteral nutrition has resulted in more patients surviving massive intestinal resection. Long-term parenteral nutrition is expensive, has potential complications, and causes inconvenience for the patient. Therefore, interest persists in surgical therapy for the short bowel syndrome. The goals of surgical therapy in the short bowel syndrome are to slow intestinal transit, increase the area of absorption, and reduce gastric hyperacidity. Patients with sufficient absorptive area, but rapid intestinal transit, benefit from antiperistaltic segments or colon interposition. Intestinal valves yield inconsistent results. Recirculating loops are associated with prohibitive morbidity and mortality. Experience with intestinal pacing is limited. Patients with dilated bowel segments may benefit from intestinal tapering or lengthening. Growing neomucosa holds promise but has not been evaluated clinically. Recent improvement in the results of intestinal transplantation in animals may warrant clinical trials. The efficacy of H2 receptor antagonists makes procedures for reducing gastric hyperacidity less necessary. None of the operations to treat the short bowel syndrome are sufficiently safe and effective to recommend their routine use. Operations should be performed only on selected patients to achieve specific goals. Although investigation continues, our emphasis should continue to be conservation of as much of the intestine as possible when massive resection is necessary.

Colon↗

Experimental non-O group 1 Vibrio cholerae gastroenteritis in humans.

In this study, 27 volunteers received one of three non-O group 1 Vibrio cholerae strains in doses as high as 10(9) CFU. Only one strain (strain C) caused diarrhea: this strain was able to colonize the gastrointestinal tract, and produced a heat-stable enterotoxin (NAG-ST). Diarrhea was not seen with a strain (strain A) that colonized the intestine but did not produce NAG-ST, nor with a strain (strain B) that produced NAG-ST but did not colonize. Persons receiving strain C had diarrhea and abdominal cramps. Diarrheal stool volumes ranged from 154 to 5,397 ml; stool samples from the patient having 5,397 ml of diarrhea were tested and found to contain NAG-ST. The median incubation period for illness was 10 h. There was a suggestion that occurrence of diarrhea was dependent on inoculum size. Immune responses to homologous outer membrane proteins, lipopolysaccharide, and whole-cell lysates were demonstrable with all three strains. Our data demonstrate that V. cholerae of O groups other than 1 are able to cause severe diarrheal disease. However, not all strains are pathogenic for humans: virulence of strain C may be dependent on its ability both to colonize the intestine and to produce a toxin such as NAG-ST.

Adolescent↗

Disseminated neonatal gastrointestinal mucormycosis: a case report and review of the literature.

Mucormycosis of the gastrointestinal tract is a rare and fatal infection of neonates and children. This report describes a case of disseminated mucormycosis originating in the gastrointestinal tract of a premature infant of 26 weeks gestational age. The antemortem impression was that of necrotizing enterocolitis, diagnosed at 15 days of age, followed by death at 22 days. However, autopsy revealed extensive colonization and invasion of the small intestine and colon by mucormycosis, with blood and peritoneal fluid cultures positive for Mucorales species but negative for bacteria. There was associated hematogenous and adjacent spread of organisms to other viscera.

Diagnosis, Differential↗

Sensitization to epithelial antigens in chronic mucosal inflammatory disease: immunochemical similarity of macromolecules in human colonic epithelium with murine intestinal epithelial cell-associated components (ECAC).

In order to explore whether human intestinal epithelium contains cell-associated components that are organ-specific and therefore potentially autoantigenic, macromolecules were isolated in aqueous-soluble form from histologically normal human colonic epithelial cells, partially purified under nondenaturing conditions, then characterized biochemically and immunologically. Preparative non-SDS-polyacrylamide gel electrophoresis followed by electro-elution into a Tris-glycine buffer separated five human colonic fractions (yield 86%), all of which possessed an acidic isoelectric point (4.0-4.8) and a modest carbohydrate content (0.9-15%), resembling fractions of corresponding Rf similarly prepared from murine colonic epithelial cells. Immunological characterization suggested that two of the gel-purified fractions (B1, B2) isolated from colonic epithelium contained organ-specific determinants: (i) reactivity of B1/B2-specific immunoglobulin was not diminished by prior absorption with proteins from other epithelial surfaces (tracheal mucosal components) nor from normal serum; (ii) epitopes on ECAC B1 and B2 fractions were shared across species lines, with reactivity for the cross-reactive determinant being as much as 20-fold that of control protein; and (iii) localization studies with specific antibody showed an organ- and cell-restricted immunofluorescence pattern on freshly fixed human and murine mucosal epithelial tissue, using B1-specific monoclonal antibody. Given the reported binding of inflammatory bowel disease serum immunoglobulin and lamina propria mononuclear cells for murine ECAC determinants, our studies suggest these same antigens are present in human colonic epithelium, and are available as potential binding sites for antibody or lymphocytes participating in an autoaggressive immune response.

Animals↗

Suppressor of cytokine signaling-2 limits intestinal growth and enterotrophic actions of IGF-I in vivo.

Suppressors of cytokine signaling (SOCS) typically limit cytokine receptor signaling via the JAK-STAT pathway. Considerable evidence demonstrates that SOCS2 limits growth hormone (GH) action on body and organ growth. Biochemical evidence that SOCS2 binds to the IGF-I receptor (IGF-IR) supports the novel possibility that SOCS2 limits IGF-I action. The current study tested the hypothesis that SOCS2 normally limits basal or IGF-I-induced intestinal growth and limits IGF-IR signaling in intestinal epithelial cells. Intestinal growth was assessed in mice homozygous for SOCS2 gene deletion (SOCS2 null) and wild-type (WT) littermates at different ages and in response to infused IGF-I or vehicle or EGF and vehicle. The effects of SOCS2 on IGF-IR signaling were examined in ex vivo cultures of SOCS2 null and WT intestine and Caco-2 cells. Compared with WT, SOCS2 null mice showed significantly enhanced small intestine and colon growth, mucosal mass, and crypt cell proliferation and decreases in radiation-induced crypt apoptosis in jejunum. SOCS2 null mice showed significantly greater growth responses to IGF-I in small intestine and colon. IGF-I-stimulated activation of IGF-IR and downstream signaling intermediates were enhanced in the intestine of SOCS2 null mice and were decreased by SOCS2 overexpression in Caco-2 cells. SOCS2 bound directly to the endogenous IGF-IR in Caco-2 cells. The intestine of SOCS2 null mice also showed enhanced growth responses to infused EGF. We conclude that SOCS2 normally limits basal and IGF-I- and EGF-induced intestinal growth in vivo and has novel inhibitory effects on the IGF-IR tyrosine kinase pathway in intestinal epithelial cells.

Aging↗