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Lymphoid cell subsets in colonic mucosa and HLA-DR antigens on colonic epithelia in colitis excluding ulcerative colitis and Crohn's disease.

Lymphoid cell subsets, including T cells as well as Ig-containing cells in the colonic mucosa and HLA-DR antigens on colonic epithelia, were examined in non-IBD colitis (colitis excluding ulcerative colitis (UC) and Crohn's disease) by the indirect immunoperoxidase staining method. Mouse anti-CD5, CD8, CD4, IgG, IgA1, IgA2, IgM, IgD, IgE, HLA-DR, and NuIa monoclonal antibodies were used as the first antibody. The results were compared to those of the normal controls and UC. T cell subsets in non-IBD colitis were almost similar to those of the controls and UC. The number of Ig-containing cells of all classes, except for IgA, tended to be increased in non-IBD colitis. In particular, both IgG- and IgE-containing cells were significantly increased compared to those in the controls. Compared to UC, IgG-containing cells were decreased in non-IBD colitis. Namely, in non-IBD colitis, as well as in UC, the change of Ig-containing cells (B cell lineage) was more pronounced than that of T cells. The frequency of the expression of HLA-DR antigens on colonic epithelia in non-IBD colitis was 70%, which was significantly higher than that in controls (0%), but significantly lower than that in UC (100%). Whether the differences in the number of IgG-containing cells, and the frequency of epithelial HLA-DR expression between non-IBD colitis and UC was due to the differences of the degree of local inflammation or due to the differences of the nature of the two diseases was not elucidated in this study.

Colitis↗

Colonic mucosal vasoactive intestinal peptide receptors in malformations of the enteric nervous system are reduced compared with morphologically normal innervated colon.

Vasoactive intestinal peptide (VIP) is the most important peptidergic transmitter in intestinal relaxation. VIPergic nerves are reduced in aganglionosis (AG). Corresponding findings in intestinal neuronal dysplasia (IND) are sparse. It is unknown whether superficial mucosal VIP receptors are reduced in AG, IND, or hypoganglionosis (HYP) compared to concentrations in morphologically normal innervated colon (MNIC). Cryostat sections from 38 colonic biopsies (23 patients with AG, IND, or HYP, 15 with MNIC) were incubated with radioactive iodinated (125)I-VIP. Receptors were analyzed by autoradiography. Radioactive-marked receptors trigger the precipitation of metallic silver as silver grains within a photographic emulsion. Grains were quantified by image analysis, calculating the percent covered cell surface. Statistical analysis was done by Mann-Whitney and Kruskal-Wallis tests (significance #E5/E5#<0.05). VIP receptors covered 4.31% of the cell surface in MNIC. The values were significantly reduced in AG (2.72%; #E5/E5#=0.012) and IND (2.93%; #E5/E5#=0.008). The two HYP biopsies showed the lowest values (1.83%). Aganglionic colon could be distinguished from healthy proximal segments and IND from habitual constipation. In AG and IND, even the superficial mucosal VIPergic innervation seems to be impaired. The reduction of mucosal VIP receptors in developmental faults of the enteric nervous system may thus be an indicator of a sensomotor disturbance.

Child, Preschool↗

Retroperitoneal perforation of the colon caused by colonic tuberculosis: report of a case.

We present a 25-year-old, HIV-negative patient from Kosovo, with no significant past medical history, who was admitted to a local hospital for nonspecific upper abdominal discomfort. He was transferred to us after a retroperitoneal mass with contact to the right colonic flexure had been found during workup. Colonoscopy demonstrated an edemateous area with a central fistula in the right flexure, and histology showed caseous necrosis. Although neither bacteriology nor histology could detect any germs, gastrointestinal tuberculosis seemed to be very probable. Laparotomy with a segmental resection of the colon was performed to remove the fistula-bearing segment, and histologic examination of the resected specimen confirmed the intraoperative suspect of a retroperitoneal colonic perforation. Again, all cultures from the specimen were negative for tuberculosis, but polymerase chain reaction of a regional lymph node revealed acid-fast bacilli of the Mycobacterium tuberculosis/bovis species. Although the patient had no other sites of tuberculosis infection like pulmonary or urinary, he received adjuvant standard tuberculosis treatment for six months. At control examination one year after the operation, the patient was free of recurrence and in very good general condition. We report this extremely rare presentation of gastrointestinal tuberculosis to sensitize physicians to tuberculosis again, because incidence rates are increasing and this disease will certainly play a more important role in the future.

Abdominal Pain↗

Healing of experimental colonic anastomoses. The effect of suture technic on collagen concentration in the colonic wall.

The present experimental study in rats has demonstrated a marked difference in the healing process of anastomoses in the left colon following two different suture technics: continuous and interrupted sutures. Rats having anastomoses constructed of continuous suture showed a high incidence of complications and a marked decrease of collagen concentration in the anastomosis and in the colonic wall proximal to the anastomosis during the first week of healing. In animals with anastomoses made of interrupted sutures there were fewer complications, the decrease in collagen concentration was confined to the anastomotic region, and the recovery of collagen concentration occurred earlier. The findings indicate that the interrupted suture technic is preferable for anastomosis in the left colon.

Animals↗

A prospective, observational study of colonic mucosal abnormalities associated with orally administered sodium phosphate for colon cleansing before colonoscopy.

BACKGROUND: Colonic mucosal abnormalities associated with sodium phosphate colonic preparations have been described. The aim of this prospective study was to determine the frequency at which these occur and to define the endoscopic and histopathologic patterns of these changes. METHODS: Within a 16-month period, 730 of patients referred for elective colonoscopy entered the study. Patients with known inflammatory bowel disease and those taking non-steroidal anti-inflammatory drugs were excluded. A sodium phosphate solution was ingested orally 14 and 8 hours before endoscopy. After standard colonoscopy, a 3-year clinical follow-up program was conducted. RESULTS: Endoscopically, mucosal lesions, possibly associated with sodium phosphate ingestion, were visible in 24 patients (3.3%). Erosions were found in 3 patients, aphthoid lesions in 21 patients, and an ulcer in one patient. Lesions often were multiple. Histopathologically, findings included focal active inflammation in 14 of 24 patients, mucosal disruption and erosion (7/24), edema of the lamina propria (5/24), mucosal hyperemia or focal hemorrhage (5/24), lymphoid nodules (5/24), and ulceration (1/24). CONCLUSIONS: Orally administered sodium phosphate-associated colonic mucosal abnormalities are infrequent but can mimic an non-steroidal anti-inflammatory drug-induced injury or inflammatory bowel disease, and in particular must be differentiated from Crohn's disease.

Cathartics↗

Total colonic aganglionosis preservation and utilization of entire colon.

Thirteen patients with total colonic aganglionosis are reported. Nine were treated with an operation to preserve and utilize the descending colon. Because of the encouraging results with this group, the operation for the four most recent infants consisted of a side-to-side anastomosis of the entire aganglionic colon to the ganglionated small bowel. The operation provides a greater surface area for absorption and also a greater area for fecal storage. All patients are continent and the ability to evacuate does not appear to have been affected.

Colon↗

A proposal to preserve the ileocecal valve and right colon in total colonic aganglionosis.

We report two cases of total colonic aganglionosis in which the ileocecal valve and right colon were preserved. The aganglionic ileal segment is removed leaving behind only a very short prececal remnant, which is anastomosed end-to-back to the remaining ileum. An ileal loop (of approximately 20 cm in length) is isolated and interposed between the right colon and rectum. The operation can be performed as a staged procedure. The advantage of preserving the ileocecal valve with respect to physiology is discussed.

Anastomosis, Surgical↗

Long-term follow-up of patients treated with ileoendorectal pull-through and right colon onlay patch for total colonic aganglionosis.

BACKGROUND/PURPOSE: This study was performed to assess the long-term follow-up of five patients who underwent one-stage ileoendorectal pull-through with right colon onlay patch for total colonic aganglionosis (TCA) at Kaiser Permanente Medical Center. METHODS: A retrospective review of inpatient and outpatient charts and telephone follow-up of all patients were conducted to obtain current data regarding growth, development, bowel function, and postoperative and late complications. RESULTS: Follow-up has ranged from 2 to 11 years. All patients are at or above the 50th percentile for weight by age and are continent with 1 to 5 daily bowel movements. Only two patients required reoperation. A perirectal abscess developed in one patient 2 months postoperatively. In the second patient a functional obstruction was relieved by sphincterotomy. CONCLUSIONS: Ileoendorectal pull-through with right colon onlay patch is associated with few early and late postoperative complications; it appears to be superior to other procedures in the early postoperative period because of the more rapid return to acceptable stooling patterns. This method of reconstruction provides an excellent opportunity for normal growth, development, and long-term bowel function.

Anastomosis, Surgical↗

Short-chain fatty acid enemas fail to decrease colonic hypersensitivity and inflammation in TNBS-induced colonic inflammation in rats.

BACKGROUND AND AIMS: Short-chain fatty acid (SCFA) (especially butyrate) enemas are widely used to reduce symptoms associated with human inflammatory bowel disease. The purpose of this study was to evaluate their real effect on colonic sensitivity in rats. METHODS: The effects of saline and SCFA enemas (acetate, propionate and particularly butyrate) were studied on visceral pain thresholds following colonic distension in control rats and in rats with colitis (instilled with trinitrobenzene sulfonic acid (TNBS)). RESULTS: Butyrate enemas (40 mM twice daily for 14 days) decreased colonic pain thresholds in control rats; they did not reduce the TNBS-induced hypersensitivity, but on the contrary increased its duration (without modifying the inflammation score). This pronociceptive effect was confirmed in control rats receiving twice daily enemas of 80 mM for 3 days and two enemas of 240 mM of a butyrate solution. The other SCFA enemas did not modify the hypersensitivity of rats with colitis and induced proinflammatory effects. CONCLUSIONS: The beneficial effect of SCFA (especially butyrate) enemas on hypersensitivity and inflammation in inflammatory bowel disease is questionable and needs to be thoroughly investigated in humans.

Acetates↗

Chitosan capsules for colon-specific drug delivery: improvement of insulin absorption from the rat colon.

The objective of this study was to estimate colon-specific insulin delivery with chitosan capsules. In vitro drug release experiments from chitosan capsules containing 5(6)-carboxyfluorescein (CF) were carried out by the Japan Pharmacopoeia (J. P.) rotating basket method with some slight modifications. The intestinal absorption of insulin was evaluated by measuring the plasma insulin levels and its hypoglycemic effects after oral administration of the chitosan capsules containing insulin and additives. Little release of CF from the capsules was observed in liquid 1, an artificial gastric juice (pH 1), or in liquid 2, an artificial intestinal juice (pH 7). However, the release of CF was markedly increased in the presence of rat cecal contents. A marked absorption of insulin and a corresponding decrease in plasma glucose levels was observed following the oral administration of these capsules that contain 20 IU of insulin and sodium glycocholate (PA% = 3.49%), as compared with the capsules containing only lactose or only 20 IU of insulin (PA% = 1.62%). The hypoglycemic effect started from 8 h after the administration of chitosan capsules when the capsules entered the colon, as evaluated by the transit time experiments with chitosan capsules. These findings suggest that chitosan capsules may be useful carriers for the colon-specific delivery of peptides including insulin.

Animals↗

Tea intake and risk of colon cancer in African-Americans and whites: North Carolina colon cancer study.

OBJECTIVES: Tea polyphenols have been shown to exhibit anti-cancer activity, but the epidemiological findings are inconsistent. We examined the association between tea consumption and colon cancer in a population-based study in North Carolina. METHODS: The analysis included 630 cases and 1040 controls frequency matched to cases by age, gender, and race. The odds ratios (OR) for tea consumption, adjusted for age and gender, were calculated for African-Americans and Whites and effect modification by race was explored. RESULTS: No association was found between tea consumption and colon cancer overall. Compared to non-consumers, those who consumed <2 servings/day or > or = 2 servings/day had OR = 0.9 (95% CI: 0.7-1.2) and OR = 1.3 (95% CI: 0.9-1.8) respectively. Other risk factors for colorectal cancer (family history of colorectal cancer, exposure to non-steroid anti-inflammatory drugs, meat cooking practices, smoking, physical activity, body mass index, intake of red meat, fruits, vegetables, and alcoholic beverages) did not influence these associations. We did not find any evidence of effect modification by race on either on the multiplicative or additive scale. CONCLUSION: We conclude that, contrary to expectation, tea drinking did not decrease the risk of colon cancer in this study population.

Adult↗

Endogenous nitric oxide release modulates the direction and frequency of colonic migrating motor complexes in the isolated mouse colon.

Spontaneous colonic migrating motor complexes (CMMCs) were recorded from circular muscle at three sites along the isolated mouse colon. The interval between CMMCs was decreased from approximately 3 min in control solution, by approximately 55% in a nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine (L-NNA; 100 micromol L-1). This was associated with a shift in migration direction of CMMCs, such that CMMCs migrated in an oral direction. Application of the endogenous substrate for NOS, L-arginine, at a low concentration used to mimic plasma concentration (134 micromol L-1), or a high concentration (5 mmol L-1) suppressed CMMCs (for at least 15 min) which were replaced by high frequency (10-15 min-1), short duration (half width approximately 1.5 s) contractions of variable amplitudes (largest in the proximal region) until CMMCs resumed. CMMCs remained in the presence of D-arginine (134 micromol L-1 and 5 mmol L-1). Apamin (250 nmol L-1) did not alter the interval between CMMCs, however, additional nonmigrating contractions were observed between the CMMCs in the distal region. In addition to its effects on smooth muscle tone, NO, but not apamin-sensitive channels, plays an important role in suppressing the frequency of migrating contractions in the isolated mouse colon. Consideration should be given to the inclusion of L-arginine, in in vitro experiments where there may be spontaneous activity in NOS containing neurones.

Animals↗

Patterns of gene expression that characterize the colonic mucosa in patients at genetic risk for colonic cancer.

We have used a computer-driven scanning and image-processing system to identify a panel of 30 cDNA clones whose pattern of expression in individual biopsy specimens distinguishes the flat, normal-appearing colonic mucosa of patients in two genetic groups at high risk for development of colorectal cancer from that of normal colonic mucosa in low-risk individuals. The two high-risk groups, familial adenomatous polyposis and hereditary nonpolyposis colon cancer, are indistinguishable based on the pattern of expression of the 30 selected clones. This suggests that the extensive pleiotropic effects of the inherited loci, which may play an important role in the mechanism of increased risk and early onset of the disease, are similar in these populations.

Adenomatous Polyposis Coli↗

Influence of dietary cis and trans fats on DMH-induced colon tumors, steroid excretion, and eicosanoid production in rats prone to colon cancer.

The effect of geometrical isomerism of dietary fats on colon tumorigenesis was studied in male and female rats of a strain prone to colon cancer (Wistar-Furth-Osaka). The rats were fed purified diets containing either partially hydrogenated corn oil (trans fat) or high-oleic safflower (cis fat) at the 5% level for one week and received a single oral dose of 1,2-dimethylhydrazine. The difference in the fatty acid composition of dietary fats was confined solely to the geometry of octadecenoate. An appropriate level of linoleic acid (2% of total energy) was supplied. After about 60 weeks, neither fat-type nor sex-dependent differences in the incidence of colon and small intestinal tumors was observed. The fecal excretion of neutral but not acidic steroids was higher in male rats fed the trans fat than in those fed the cis fat, but the composition remained almost unchanged. Aortic production of prostacyclin and the plasma concentration of thromboxane B2 were not influenced by dietary fats, although these were significantly higher in females, irregardless of the fat source. Thus, trans fat behaved much like the cis fat in various parameters, except for steroid excretion.

Animals↗

Dietary soybean protein compared with casein damages colonic epithelium and stimulates colonic epithelial proliferation in rats.

Recently we showed that soybean protein compared with casein stimulates the fecal excretion of endogenous magnesium. In the present study we investigated whether this differential effect of soybean protein is due to intestinal epithelial cell damage and thus results in a compensating increase in proliferation of epithelial cells. Two groups of six rats were fed purified high fat, low calcium diets, differing only in the type of protein. When compared with casein feeding, soybean protein feeding stimulated the fecal excretion of magnesium, fat and fatty acids, but had no effect on the excretion of bile acids. In fecal water, the concentration of bile acids was lower when soybean protein was fed. In contrast, free fatty acid concentration, as well as luminal cytolytic activity, was higher in fecal water of rats fed soybean protein. Furthermore, epithelial cell damage and proliferation of colonic epithelium (measured as in vivo incorporation of tritiated thymidine into DNA) were greater in rats fed soybean protein. The stimulation of colonic proliferation by soybean protein is consistent with the observed increase in luminal cytolytic activity and epithelial cell damage. We conclude that the stimulatory effect of soybean protein on endogenous magnesium excretion is due to a soybean protein-specific damage of colonic epithelial cells, which results in a compensatory epithelial cell hyperproliferation.

Animals↗

Increased colonic luminal synthesis of butyric acid is associated with lowered colonic cell proliferation in piglets.

Butyrate inhibits colonic cell proliferation in vitro but reportedly has an opposite effect in vivo. Because lactulose feeding decreases cecal cell proliferation, an effect attenuated by prefeeding inulin, we hypothesized that lactulose feeding would decrease colonic luminal synthesis of butyrate, and that prefeeding and cofeeding inulin would prevent this effect. Piglets (n = 31) were catheterized and randomly assigned to 1 of 4 groups: Control formula (C); control formula + lactulose (L); control formula + lactulose + inulin (L + I); and control formula + inulin (I). At 6 and 7 d postsurgery, the rate of cecal synthesis of butyrate, cecal cell proliferation and apoptosis, and cecal and distal colon butyrate concentration were measured. In groups C, L, L + I, and I, the rates of synthesis of butyrate (mean +/- SEM) were 10.6 +/- 3.2, 23.3 +/- 4.5, 12.4 +/- 3.6, and 14.6 +/- 4.0 micromol/min, respectively (Group Effect, P = 0.1; C vs. L, P = 0.03; L vs. L + I, P = 0.06). The cecal butyrate concentrations did not differ among the 4 groups and were 8.7 +/- 3.2, 2.4 +/- 0.8, 3.4 +/- 1.9, and 2.0 +/- 0.7 micromol/g dry wt, respectively. The total cecal cell proliferation index was higher in C than in L (P = 0.008) or I (P = 0.026) and was higher in L + I than in L (P = 0.013) or I (P = 0.046). The increased supply of butyrate to the cecum was associated with decreased cell proliferation, but cecal butyrate concentration did not reflect synthesis.

Animals↗

Fractured colon: an endoscopically distinctive lesion associated with colonic perforation following colonoscopy in patients with collagenous colitis.

BACKGROUND: Collagenous colitis is characterized by collagen deposition in the superficial colonic mucosa, beneath the surface epithelium, resulting in chronic nonbloody diarrhea of variable severity. The mucosa generally appears endoscopically normal. METHODS: We report the occurrence of distinctive linear mucosal tears, unassociated with trauma, in 4 patients during diagnostic colonoscopy. The patients' tissue specimens were examined histologically, and clinical courses were recorded. OBSERVATIONS: Recognition of linear "fractures" was followed in 3 patients by colonic perforation. One patient required colectomy. Severe collagenous colitis was present in all. The resection specimen contained shallow linear ulcers overlying fibrotic submucosa, with pneumatosis and acute peritonitis. CONCLUSIONS: We theorize that the stiffness of the colon in areas of collagenous colitis with submucosal fibrosis makes it susceptible to linear "fractures" during colonoscopic air insufflation with subsequent transmural air dissection. We urge extreme caution if this lesion is recognized at colonoscopy and recommend aborting the examination and obtaining plain radiographs to detect free intraperitoneal air.

Aged↗

Epithelial cell proliferation of the colonic mucosa in different degrees of colonic diverticular disease.

GOAL: This study assesses the epithelial cell proliferation in different degrees of diverticular disease and compares this with two different control groups. BACKGROUND: Hyperproliferation of the colonic mucosa has been recently described in diverticular disease (DD), but it is unknown whether this finding is present in every degree of DD. PATIENTS AND METHODS: Thirty consecutive patients with a new endoscopic diagnosis of DD (10 with asymptomatic diverticulosis, 10 with symptomatic uncomplicated DD, and 10 with acute uncomplicated diverticulitis) were enrolled. Ten matched healthy people and 10 patients with ulcerative colitis (UC) (5 with UC in remission and 5 with active UC) were enrolled as control groups. The Ki-67 antigen index of the whole crypt and the upper third was separately evaluated. RESULTS: Ki-67 index of the whole crypt and the upper third of the crypt was significantly higher in all degrees of DD compared with the healthy control group. In particular, asymptomatic diverticulosis showed a threefold higher Ki-67 index compared with that of the healthy control group (5.4% and 5.6% vs. 1.6% and 1.8%, respectively, P = 0.005), and similar to that of UC in remission (5.4% and 5.6% vs. 5.9% and 5.8%, respectively, P = not significant). CONCLUSIONS: We found an upward shifting of cellular proliferation of the colonic mucosa in patients with different degrees of DD. In particular, asymptomatic diverticulosis seems to show the same risk for colonic carcinoma as that of UC.

Cell Proliferation↗