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PubMed1976

Implications of precancerous rectal biopsy in patients with inflammatory bowel disease.

Sixty-five patients with an initial diagnosis of ulcerative colitis who underwent total proctocolectomy between 1955 and 1973 were studied retrospectively. Rectal mucosa in each patient was examined microscopically for the presence or absence of "precancerous" alterations as described by Morson and Pang. Histologic examination was made with no knowledge of concomitant colon carcinoma or the patients' clinical courses. Three of ten patients with precancerous rectal mucosa had invasive colon carcinoma, while none of the 55 patients without such changes had colon cancer (P less than .05, Fischer exact test). The duration of disease was significantly greater in those patients with rectal precancer (P less than .05). Reexamination changed the pathologic diagnosis in 15 patients from ulcerative colitis to granulomatous or "mixed" colitis. Two of three invasive cancers occurred in the reclassified group. Results support previous contentions that careful histologic evaluation of rectal biopsy specimens from individuals with inflammatory bowel disease may better define that population of patients with an increased risk of colonic carcinoma.

Colitis↗
PubMed1997

Rutoside as mucosal protective in acetic acid-induced rat colitis.

The effect of the flavonoid rutoside on acetic acid-induced rat colitis was studied. Rats were pretreated orally with different doses of the flavonoid (10, 25, and 100 mg/kg) 48, 24, and 1 hour prior to colitis induction and examined for colonic damage 24 hours later. Colonic inflammation was characterized by gross and microscopical injury, bowel wall thickening, abolition of fluid absorption, glutathione depletion, enhanced leukotriene B4 synthesis, and increased levels of myeloperoxidase and alkaline phosphatase activities. Rutoside treatment (25 and 100 mg/kg) reduced histologic injury and prevented the increase in alkaline phosphatase activity, but it had no effect on myeloperoxidase levels or leukotriene B4 synthesis. In addition, glutathione depletion was effectively counteracted at the dose of 25 mg/kg, whereas fluid absorption was achieved at the highest dose assayed. It is concluded that rutoside has an acute anti-inflammatory activity in this model which may be related to a putative direct protective effect on intestinal cells, mainly enterocytes, in which the antioxidative properties of the flavonoid may play a role.

Acetic Acid↗
PubMed2005

Adoptive transfer of NK 1.1+ lymphocytes in immune-mediated colitis: a pro-inflammatory or a tolerizing subgroup of cells?

UNLABELLED: T lymphocytes expressing NK1.1 marker (NKT) have been suggested to play crucial roles in immune modulation. AIM: To determine the role of NK1.1+ cells in induction and maintenance of pro-inflammatory and/or tolerizing responses. METHODS: Colitis was induced in C57/B6 donor mice by intracolonic instillation of trinitrobenzenesulfonic acid (TNBS). Donor mice received five oral doses of colonic proteins extracted from TNBS-colitis colonic wall. Depletion of NK1.1+ lymphocytes was performed before lymphocyte harvesting. Splenocytes were harvested and separated into T-cell subpopulations, and transplanted into recipient mice before intracolonic instillation of TNBS. Standard clinical, macroscopic, and microscopic scores, and intracellular staining, flow cytometry, and cytotoxicity assays were performed. RESULTS: The adoptive transfer of CD4+ and NK1.1+ cells harvested from tolerized mice markedly ameliorated the colitis in recipient mice. In contrast, the adoptive transfer of CD8+ and double negative lymphocytes failed to transfer the tolerance. Recipients of splenocytes from tolerized mice exhibited an increase in CD4+ IL4+/CD4+ IFNgamma+ ratio. In contrast, recipients of splenocytes from NK1.1-depleted-tolerized mice exhibited severe colitis with a significant decrease of the CD4+ IL4+/CD4+ IFNgamma+ ratio. However adoptive transfer of splenocytes from non-tolerized NKT-depleted mice led to an alleviation of colitis with a relative increase of the CD4+ IL4+/CD4+ IFNgamma+ ratio. CONCLUSIONS: NK1.1+ lymphocytes play a critical role in immune regulation. They may be accountable for an alteration of the inflammatory response and the CD4+ IL4+/CD4+ IFNgamma ratio immune-mediated colitis and in peripheral tolerance induction.

Adoptive Transfer↗
PubMed1988

[Diffuse pseudopolyposis of the colon: developmental form or cicatricial of hemorrhagic rectocolitis?].

The authors report the case of a patient with generalized polyposis associated with ulcerative colitis. The diagnosis of polyposis was made 20 years after the onset of colitis. The patient presented with the unusual clinical manifestations, ie poor general condition and severe denutrition, following a severe relapse of colitis. The mucosal surface of the entire colon, except the rectum, was covered by innumerable polyps, without any macroscopic or microscopic evidence of ulceration. Intestinal protein loss, as assessed by alpha-1-antitrypsin clearance, was very high (470 ml/d). Acute mucosal inflammation, as assessed by histologic study and by 111-Indium-labelled-leukocyte scintigraphy, was also present. The patient responded dramatically to total colectomy with ileorectal anastomosis. Histologically, the polyps were filiform, with a central core, containing vessels and smooth muscle fibers. This observation demonstrates that generalized polyposis, generally considered to be an asymptomatic sequela of ulcerative colitis, can also be associated with severe attacks of colitis.

Adult↗
PubMed1990

A simple index for assessment of disease activity in patients with ulcerative colitis.

Based upon data from a prospective series of 61 patients with ulcerative colitis, most of them with the mild or quiescent form, a simple index for assessment of the disease's activity was devised. The activity index was the sum of three different scores evaluating history, macroscopic findings at endoscopy and microscopic findings in biopsy specimens, respectively. The index was consistent in itself and it may be of value in assessing spontaneous or drug-dependent variations in ulcerative colitis. The serum protein C1 inhibitor, belonging to the acute phase reactants, could not be shown to correlate significantly with the activity index or any of its components.

Adult↗
PubMed1997

Gastroenteric inflammation in children with ulcerative colitis.

This is a retrospective review of five pediatric cases of inflammatory bowel disease with gastroduodenal as well as pancolonic inflammation. The presumptive diagnosis was Crohn's disease in all. Three of five also had microscopic ileitis. Chronic active gastritis was present at diagnosis in all five and duodenitis in four of five. None ever had noncaseating granulomas in any location. Prolonged (mean, 22 months) and ineffective trials of multiple medical therapies were carried out before subtotal proctocolectomy, which allowed the diagnosis of ulcerative colitis to be made in all children. Surgery remained curative after follow-up of over 1 yr (mean, 16 months). This experience confirms that gastroduodenal inflammation occurs in children with ulcerative colitis. Presence of gastroduodenal inflammation does not ensure the diagnosis of Crohn's unless other characteristic features of Crohn's are present. Accurate discrimination between Crohn's and ulcerative colitis remains important in management of pediatric inflammatory bowel disease to facilitate timely surgical referral. Upper gastrointestinal tract inflammation in ulcerative colitis warrants further study.

Adolescent↗
PubMed2000

Experimental inflammatory bowel disease--role of T cells.

BACKGROUND: Our experiments were aimed to test: 1. which lymphocyte subpopulations participate in mouse colitis, produced by intrarectal (i.r.) deposition of trinitrobenzene sulphonic acid (TNBSA, TNP hapten); 2. the expression of cell adhesion molecules on lymphocytes draining the site of reaction; 3. the influence of mouse haplotype on the development of colitis. METHODS: CBA/J, BALB/c and C57BI/6 inbred and outbred Swiss Webster strains were used. Mesentheric lymph node (MLN) cells of immunized animals, unseparated or separated into CD4+, CD8+ or gammadelta+ and alphabeta+ T cell subpopulations or depleted of B lymphocytes, were transferred into recipients which were challenged i.r. with TNBSA. Inflammatory reaction in the colon was confirmed macro- and microscopically and by myeloperoxidase (MPO) level. MLN lymphocyte surface markers were tested cytofluorimetrically using appropriate antibodies. RESULTS: Sensitization with TNP results in chronic colitis (hapten dose-dependent colon weight gain and cellular infiltrate, significant increase of MPO level) only in CBA/J and BALB/c strains and can be adoptively transferred in a cell-dose dependent manner into syngeneic recipients by T alphabeta+ cells of both CD4+ and CD8+ subpopulations. T gammadelta+ cells were ineffective and B lymphocytes do not participate in the passive transfer reaction. In MLN the number of T lymphocytes positive for cell adhesion molecules particularly LPAM-1 (V-CAM1) and LPAM-2 increases significantly. CONCLUSIONS: Both CD4+ and CD8+ lymphocytes participate in the development of TNP-induced colitis. High MPO level may suggests that both Th1 and Th2 cells are involved. Colitis is accompanied by a significant accumulation in MLN of T lymphocytes positive for several cell surface adhesion molecules characteristic for memory T cells. Significant differences in susceptibility to develop colitis were found between different strains of mice.

Animals↗
PubMedDate not supplied

[Focal segmental glomerulosclerosis with IgA deposits in a patient with ulcerative colitis].

BACKGROUND: Glomerular diseases are described in patients with active ulcerative colitis (UC). Likely drug-induced interstitial nephritis, and nephrotic syndrome due to minimal change disease, have been reported in a few patients with UC on treatment with mesalazine and sulfasalazine (5-ASA). We describe a 33 year-old patient with a 5-years history of UC who recently developed nephrotic syndrome associated with microscopic haematuria. Blood pressure and renal function were normal. The patient was on azathioprine (AZA), mesalazine and sulfasalazine during the last year for his colitis, with good control of bowel disease. Renal biopsy revealed a focal segmental glomerulosclerosis (FSGS) associated with mesangial IgA deposits; no signs of interstitial nephritis were found. 5-ASA was discontinued, AZA was reduced and a rapid remission of the nephrotic syndrome was observed after 6 weeks of steroid therapy (1 mg/kg/day per os) associated with ramipril 5 mg/day, with a follow-up of 9 months. CONCLUSIONS: To our knowledge this is the first report of UC and GSFS associated with IgA deposits. The occurrence of nephrotic syndrome during UC is suggestive of an association between UC and FSGS, but a possible role of mesalazine and /or sulfasalazine in its pathogenesis cannot be excluded. Mesangial IgA deposits could be an "occasional" further occurrence, considering the chronic inflammation of colonic mucosa and the altered immune response of patients with UC.

Adult↗
PubMed1983

Macroscopic lesions in dysplasia and carcinoma complicating ulcerative colitis.

Visible changes associated with dysplasia or carcinoma have been assessed in 62 colectomy specimens from patients with ulcerative colitis. In 34 colectomy specimens with one or more carcinomas, there were 51 visible carcinomas and 65 macroscopic dysplastic lesions; only one carcinoma was found in flat mucosa. Among 28 specimens with microscopic dysplasia but no carcinoma, eight contained no visible dysplastic lesion, and the remaining 20 contained a total of 40 polypoid or elevated dysplastic areas. In 32 operative specimens removed for long-standing chronic colitis without dysplasia or carcinoma, nine contained visible inflammatory polypoid lesions. On radiological or endoscopic examination of the colon in long-standing colitis close attention should be given to the identification and biopsy of polyps, elevated nodular areas or plaques, strictures, and isolated ulcers. It is likely that colectomy specimens with visible polypoid or elevated dysplastic lesions will contain a carcinoma more often than those removed for dysplasia in flat mucosa.

Carcinoma↗
PubMed2006

High-magnification chromoscopic colonoscopy in ulcerative colitis: a valid tool for in vivo optical biopsy and assessment of disease extent.

BACKGROUND AND STUDY AIMS: Colonoscopy with mucosal biopsy is currently considered to be the "gold standard" investigation for the evaluation of disease activity and disease extent in ulcerative colitis. Conventional colonoscopic criteria are inadequate for assessing disease extent and for predicting clinical relapse, however. Histopathological markers of relapse, such as microscopic crypt abscess formation and mucin depletion cannot be identified using conventional endoscopy. The aim of this study was to evaluate the efficacy of high-magnification chromoscopic colonoscopy for the in vivo assessment of histopathological inflammation and disease extent using standardised endoscopic and histopathological criteria. PATIENTS AND METHODS: Total colonoscopy using the Olympus CF240Z magnifying colonoscope was performed prospectively in 325 consecutive patients with a known diagnosis of ulcerative colitis. A "biphasic" examination of all five colonic segments and the rectum was performed with conventional endoscopy followed by magnification imaging and biopsy. Disease activity was documented using Baron's classification, modified Saitoh criteria for magnification imaging, and Matts' histopathological grading. RESULTS: A total of 1800 images from 300 patients were analyzed (25 patients were excluded). The kappa coefficients of agreement between Saitoh's magnification criteria grades 1/2, 3/4, and 5/6 and Matts' histopathological grades 1/2, 3a/b, and 4/5 were 0.96, 0.62, and 0.51, respectively. Mild, moderate, and severe histopathological disease (Matts' grades 1/2, 3a - 4, and 5) were represented more accurately using Saitoh's criteria than by conventional Baron scores for all clinical parameters ( R = 0.976; P < 0.001). Magnification imaging was significantly better than conventional colonoscopy for predicting disease extent in vivo ( P < 0.0001). CONCLUSIONS: This is the largest prospective study and the only Western group to report on this application of magnification imaging. High-magnification imaging provides a sensitive and specific in vivo "virtual biopsy" in ulcerative colitis and so an instant biomarker for disease relapse, while accurately predicting disease extent. High-accuracy optical biopsy can limit the number of biopsies required, with significant cost savings for pathology services.

Adolescent↗
PubMed1991

Immunohistochemical characterization, distribution, and ultrastructure of lymphocytes bearing T-cell receptor gamma/delta in inflammatory bowel disease.

Phenotypic characterization and distribution of gamma/delta T lymphocytes in the intestinal mucosa were investigated in ulcerative colitis and Crohn's disease by immunohistochemistry. The ratio of delta(+) cells to CD3(+) cells in the intraepithelial space of colon was decreased in Crohn's disease (13%) and strikingly decreased in ulcerative colitis (8%) compared with the control (36%). Delta(+) cells in the lamina propria were also decreased, particularly in the distal ileum of Crohn's disease (4%), compared with the control (15%). On the contrary, the cells gathered at the severe inflammatory sites with other inflammatory cells, including beta(+) cells, and were densely distributed in the T-cell zone around lymphoid follicles. Phenotypic characterization showed that delta(+) lamina proprial lymphocytes of colon were mainly CD4(-)CD8(-) in the control (80%) and Crohn's disease (59%). However, in ulcerative colitis, CD4(-)CD8(-) delta(+) lymphocytes were rarely found (3%). This reflects the difference of immunologic background between the two diseases. Immunoelectron microscopically, these cells in inflammatory bowel disease were rich with vesicular structures in cytoplasms, whereas those in the control group contained electron-opaque granules. The decrease and the morphological change may be closely related to the weakness of mucosal defense.

Adult↗
PubMed1983

Circulating antibodies to the surface antigens on colon epithelial cells in ulcerative colitis.

The fluorescence activated cell sorter (FACS) was used for detecting circulating antibodies to the surface antigens on isolated colon epithelial cells (anti-colon antibodies) by indirect immunofluorescence. Anti-colon antibodies were found in the serum of 30 of 41 (73%) patients with ulcerative colitis. This incidence is much higher than one established in earlier reports by application of indirect immunofluorescence to colon tissue using the fluorescence microscope. The results suggest that FACS analysis is very useful for detecting antibodies to colon specific antigen.

Adult↗
PubMed2005

The effect of angiotensin-converting enzyme inhibitors on experimental colitis in rats.

The present study was aimed to investigate the effect of ACE inhibition on trinitrobenzene sulphonic acid (TNBS)-induced colonic inflammation in rats by using captopril and lisinopril. In treatment groups, the rats were treated with ACE inhibitors, captopril or lisinopril (0.1 and 1 mg/kg/day; intraperitoneally). The drugs were given 5 min after induction of colitis and the treatment was continued for 3 days. Three days after the induction of colitis, all rats were decapitated. The distal colon was weighed and the mucosal lesions were scored at both macroscopical at microscopic levels. Malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content were assessed in tissue samples. Formation of reactive oxygen species in colonic samples was monitored by using chemiluminescence technique. Serum TNF-alphalevel was assessed in trunk blood. Captopril treatment was found to be beneficial in all parameters, except colonic glutathione content. On the other hand, although stimulation of lipid peroxidation and increase in serum TNF-alpha level were successfully prevented by lisinopril, the morphology of the lesions remained unchanged. In conclusion, sulphydryl and non-sulphydryl ACE inhibitors, captopril and lisinopril do not seem to be similarly effective in TNBS-induced colitis model at least at the doses tested in our study.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

The occurrence of diversion colitis in patients with a sigmoid neovagina.

Diversion colitis is an inflammatory process occurring in segments of the colorectum surgically diverted from the fecal stream. Clinical symptoms of this condition are rectal discomfort, pain, discharge, and bleeding. We diverted isolated segments of sigmoid to create neovaginas in patients with aplasia vaginae and in male to female transsexuals. In contrast to what is reported in most studies of diversion colitis, the neovagina consists of an isolated segment not connected to the anus in patients without any pre-existing bowel disease. To investigate the occurrence of diversion colitis in these sigmoid-neovaginas we studied biopsy specimens from 13 patients. Most of the patients complained of discharge and slight blood loss from their sigmoid-neovagina. Microscopic examination of the biopsy specimens showed lymphocytic infiltration in all cases. Four cases showed an acute inflammatory infiltrate in the lamina propria. Our results indicate that the changes observed on clinical and histopathologic examinations represent the entity of mild diversion colitis. We conclude that diversion colitis also occurs in a sigmoid neovagina.

Adult↗
PubMed1995

Porcine colonic spirochetosis: a retrospective study of eleven cases.

This retrospective study of porcine colonic spirochetosis was done in order to characterize the clinical signs, the macroscopical and microscopical changes, and the bacteriological results of cases observed in Quebec. Necropsy records of all cases of colitis were reviewed. Eleven cases with filamentous bacteria colonizing the colonic epithelium were selected. This condition was only observed in weaned piglets, and was associated with mild persistent diarrhea and growth retardation. Macroscopic changes were generally limited to the presence of soft to liquid colonic contents. Adherence of filamentous helicoidal bacteria to the apical surface of the colonic epithelium and mild diffuse infiltration of the colonic lamina propria by mononuclear cells were the main histological findings. Weakly beta-hemolytic spirochetes were isolated in 6 cases. This condition seems to be underestimated for various reasons, and it is possible that some cases diagnosed as nonspecific colitis or superficial colitis, in fact, represent later stages of porcine colonic spirochetosis.

Animals↗
PubMed1997

Histological changes in the colonic mucosa following irrigation with short-chain fatty acids.

OBJECTIVES: Short-chain fatty acids (SCFAs) derived from bacterial fermentation of complex carbohydrates are preferred luminal nutrients of the colonic mucosa. Starvation of colonocytes through lack or impaired metabolism of luminal SCFAs may be a cofactor in the pathogenesis of ulcerative colitis. DESIGN: A detailed histological evaluation of colonic biopsy specimens was performed in patients with active distal ulcerative colitis who were treated with rectal enemas containing a mixture of SCFAs, n-butyrate alone or saline placebo. Together with light microscopic parameters of mucosal inflammation, the pattern of crypt cell proliferation (proliferating cell nuclear antigen) and the mucosal activity of factor XIII were assessed. RESULTS: Butyrate reduced the density of polymorphonuclear leucocytes in the lamina propria (4 weeks: P = 0.063; 8 weeks: P = 0.091); other inflammatory parameters remained unchanged. Both butyrate and the SCFA mixture reduced significantly the number of proliferating cells in the upper 40% of crypts. Tissue factor XIII activity in active ulcerative colitis was significantly lower than in mucosa from normal colons; however, it was not affected by SCFA or butyrate irrigation. CONCLUSION: SCFAs and butyrate have a more marked effect on crypt cell proliferation than on parameters of inflammation in patients with active ulcerative colitis.

Adult↗
PubMed2005

Mucosal colonisation with Lactobacillus casei mitigates barrier injury induced by exposure to trinitronbenzene sulphonic acid.

BACKGROUND: Trinitrobenzene sulphonic acid (TNBS) induces chronic transmural inflammatory lesions in the rat colon. Injury is facilitated by barrier disruption and invasion of commensal bacteria. However, certain bacteria have shown anti-inflammatory properties in in vitro models. AIM: To investigate in vivo the anti-inflammatory effect of Lactobacillus casei DN-114 001. METHODS: Rats with a colonic segment excluded from faecal transit were surgically prepared. After washing the lumen with antibiotics, the excluded segment was recolonized (control group: standard flora of rat origin; test group: standard flora and L casei). Microbial colonisation was confirmed by culture of segment washing, and colitis was then induced by instillation of TNBS. One day after, intestinal lesions were blindly graded by macro- and microscopic scores, and myeloperoxidase activity measured in tissue homogenates. Translocation of bacteria to mesenteric lymph nodes, spleen and liver was investigated. RESULTS: Test rats showed a smaller area of mucosal injury than control rats (p<0.05). Maximum depth lesion scores were similar in both groups but myeloperoxidase activity was lower in test than in control rats (p<0.05). Remarkably, bacterial translocation was quantitatively lower (p<0.01) and less frequent (p<0.05) in test than in control rats. CONCLUSION: In rats colonised with L casei, mucosal injury, inflammatory response, and barrier disruption after TNBS challenge were attenuated. Bacterial communities colonising the mucosa can modify inflammatory responses to luminal challenges.

Animals↗
PubMed1996

Effect of bucillamine on the rat trinitrobenzene sulfonic acid induced model of colitis.

Salicylazosulphapyridine and corticosteroids are the only remedies for inflammatory bowel disease currently in clinical use. They do not, however, necessarily bring about satisfactory therapeutic benefits, so that new agents are needed. In this study, we evaluated the effect of bucillamine, a new antirheumatic agent, in experimental rat colitis induced by trinitrobenzene sulfonic acid enema. Wistar rats were given vehicle alone (n = 16) or treated with 50 (n = 20) or 150 (n = 20) mg/kg of bucillamine daily for three weeks after induction of colitis. Conventional histological sections of the colon stained by haematoxylin and eosin were prepared and observed under a light microscope to determine colonic damage scores. The determinations were significantly lower in the group treated with 50 mg/kg of bucillamine and tended to be lower in the group treated with 150 mg/kg of bucillamine than in the untreated group, which implied that the experimentally induced colonic inflammatory changes and ulcerations were alleviated by bucillamine. Blood tests showed no abnormal values at the end of the treatment. The present observations suggest that bucillamine should be developed further as a possible therapy for inflammatory bowel disease.

Animals↗