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PubMed1998

Fulminant colitis in inflammatory bowel disease: detailed pathologic and clinical analysis.

PURPOSE: The morphologic features of fulminant colitis may be nonspecific, making differentiation between ulcerative colitis and Crohn's disease difficult, even after colectomy. The aims of this study were 1) to identify histologic features that accurately differentiated ulcerative colitis, Crohn's disease, and indeterminate colitis in fulminant colectomy specimens; 2) to determine how frequently subsequent clinical course altered the pathologic diagnosis; and 3) to evaluate the natural history of histologically diagnosed indeterminate colitis. METHODS: Ninety-five fulminant colectomy specimens were evaluated, of which 85 had an original diagnosis of fulminant inflammatory bowel disease. Complete pathologic material and comprehensive clinical follow-up information was available on 67 cases of inflammatory bowel disease. These were re-evaluated in a blinded fashion, and histopathologic features were compared with the original diagnosis and reviewed in the light of subsequent clinical behavior to reach a final diagnosis. RESULTS: Evaluation of macroscopic features was not helpful in differentiating ulcerative colitis from Crohn's disease. Microscopic examination correctly diagnosed ulcerative colitis or Crohn's disease in only 58 of 67 (87 percent) cases. A further three cases (4 percent) were definitively classified after correlation with clinical data, leaving a residual six cases that were diagnosed as indeterminate colitis. Granulomas and lymphoid aggregates were the two most specific indicators of Crohn's disease. CONCLUSIONS: Histopathologic evaluation alone has limitations in the accurate classification of fulminant inflammatory bowel disease. Histologically diagnosed indeterminate colitis is a heterogeneous group that may include some patients who subsequently prove to have ulcerative colitis or Crohn's disease.

Adolescent↗

PubMed1990

Increased colonic mucosal angiotensin I and II concentrations in Crohn's colitis.

To define a potential role for the angiotensin system in Crohn's colitis, the colonic mucosal levels of angiotensin I and II were measured in endoscopic biopsy samples from patients with active Crohn's colitis (n = 20), ulcerative colitis (n = 13), other forms of colitis (n = 3), and normal controls (n = 17). Colonic mucosal levels of angiotensin I and II were greater in patients with Crohn's colitis than in normal subjects (p less than 0.001 and p less than 0.001, respectively). Mucosal levels of angiotensin I and II were also higher in Crohn's colitis than in ulcerative colitis (p less than 0.001 and p less than 0.001, respectively), and levels of angiotensin II were higher in Crohn's than in other forms of colitis (p = 0.014). Mucosal levels of angiotensin I and II correlated well with the degree of macroscopic inflammation in Crohn's colitis (r = 0.86, p less than 0.001 and r = 0.68, p less than 0.001, respectively). Mucosal levels of angiotensin I correlated fairly well with the Crohn's Disease Activity Index (r = 0.46, p less than 0.05) while angiotensin II levels correlated poorly. These studies suggest that angiotensin I and II may have a role in the inflammation associated with Crohn's colitis.

Angiotensin I↗

PubMed2005

Activation of nuclear factor kappaB in colonic mucosa from patients with collagenous and ulcerative colitis.

BACKGROUND AND AIMS: Expression of inducible nitric oxide synthase (iNOS) is greatly upregulated in the colonic mucosa of patients with collagenous and ulcerative colitis. As the transcription factor nuclear factor kappaB (NFkappaB) is a major inducer of iNOS gene expression, we compared activation and transcriptional activity of NFkappaB in colonic mucosal biopsies from these patients. PATIENTS: Eight patients with collagenous colitis, six with relapsing ulcerative colitis, and eight with uninflamed bowel were studied. METHODS: NFkappaB DNA binding activity was assessed by electrophoretic mobility shift assay and inhibitor of NFkappaB (IkappaB) kinase (IKK) activity by immunocomplex kinase assay. In vivo recruitment of NFkappaB to the iNOS promoter was determined by chromatin immunoprecipitation analysis and transcriptional activity by NFkappaB gene expression profiling arrays. Cells showing NFkappaB activation were identified by immunohistochemistry. RESULTS: In collagenous and ulcerative colitis, as opposed to uninflamed bowel, IKKbeta activity and strong NFkappaB DNA binding gave rise to activation of identical NFkappaB subunits and recruitment of transcriptionally active p65 to the iNOS promoter. In collagenous colitis, activated NFkappaB was observed only in epithelial cells while up to 10% of lamina propria macrophages showed activation in ulcerative colitis. CONCLUSIONS: In collagenous and ulcerative colitis, colonic mucosal NFkappaB is activated and recruited to the iNOS promoter in vivo via an IKKbeta mediated pathway. As collagenous colitis is not associated with tissue injury, these data challenge the prevailing view that activation of NFkappaB per se mediates tissue injury. Our results suggest that downstream inflammatory reactions leading to tissue damage originate in lamina propria immune cells, as increased NFkappaB activity in collagenous colitis was localised solely in epithelial cells, but present also in macrophages in ulcerative colitis.

Colitis, Collagenous↗

PubMed1980

Increased incidence of faecal coliforms with in vitro adhesive and invasive properties in patients with ulcerative colitis.

Faecal samples were collected from 23 patients with active ulcerative colitis, 15 patients with established ulcerative colitis in remission, 20 patients with active colitis of cause other than ulcerative colitis, and 20 normal control subjects. Ten coliform colonies were randomly selected from the faecal sample cultures and serotyped before the testing of each different serotype from each sample for adhesive or invasive properties on HeLa cell monolayers. In the patients with both active ulcerative colitis and ulcerative colitis in remission and those with other types of colitis one serotype tended to dominate the faecal coliform flora. In normal controls more variety was encountered. Thirty-five per cent of the patients with active ulcerative colitis and 27% of the patients with ulcerative colitis in remission had at least one adhesive or invasive faecal coliform as compared with 5% of the patients with other types of colitis and 5% of the normal controls. These findings are significant (P < 0.05) and may have aetiological and therapeutic significance.

Adhesiveness↗

PubMed2005

Microscopic colitis: a report of two cases.

Microscopic colitis is characterized by chronic, watery, secretory diarrhea, with a normal or near-normal gross appearance of the colonic mucosa. Biopsy is diagnostic and usually reveals either lymphocytic colitis or collagenous colitis. The symptoms of collagenous colitis appear most commonly in the sixth decade. With collagenous colitis, the major microscopic characteristic is a thickened collagen layer beneath the colonic mucosa, and with lymphocytic colitis, an increase number of intraepithelial lymphocytes. Clinically, collagenous colitis is characterized by long-standing diarrhea. In patients with lymphocytic colitis, the duration of diarrhea is usually shorter and female predominance is less apparent. We report two cases of lymphocytic colitis in elderly women. Both presented with watery diarrhea of two month duration and weight loss. Extensive investigations were done and several medications failed to stop their diarrhea. Biopsy revealed lymphocytic colitis. Their diarrhea responded well to cholestyramine.

Aged↗

PubMed1985

Endoscopic, histological and ultrastructural correlations in the diagnosis of colitis.

The accuracy of the endoscopic diagnosis, found at fiberoptic distal-colonoscopy, was assessed by correlation with the histological findings of multiple colo-rectal biopsies. Of 25 subjects with normal colon at endoscopy, 18 (72%) had normal histology, while 7 (28%) had histological evidence of mild non-specific colitis (6 cases) or Crohn's colitis (one case). Of 15 cases with endoscopic appearance of mild colitis, histological sections showed mild non-specific colitis in 12 (80%), idiopathic ulcerative colitis in one and Crohn's colitis in another. In 12 patients with an endoscopic diagnosis of moderate-severe colitis, histology confirmed moderate to severe idiopathic ulcerative colitis in 9 (75%) and severe Crohn's colitis in 2. Pseudomembranous colitis was confirmed by histology in 2 out of 3 cases detected by endoscopy. Electron-microscopy, although amplifying the histological findings, did not provide any specific diagnostic information. It is concluded that histological studies of multiple colo-rectal biopsies can significantly improve the diagnostic accuracy of distal-colonoscopy. Biopsies should therefore be obtained routinely in colonoscopy even if the appearances look normal.

Adult↗

PubMed1993

[What is the prognosis in unclassified colitis? Results of a cohort study of 104 patients in the Northern-Pas-de-Calais region].

Acute unclassified colitis could be the first attack of inflammatory bowel disease, particularly chronic ulcerative colitis or acute non specific colitis regarded as being of infectious origin without recurrence. The aim of this work was to determine the outcome of 104 incidental cases of acute unclassified colitis diagnosed during the year 1988 at a census point made 2.5 to 3 years later and to search for demographic and clinical discriminating data for final diagnosis. Thirteen patients (12.5%) were lost to follow up. Another final diagnosis was made in three other patients: two had salmonellosis and one diverticulosis. Of the remaining 88 patients, 46 (52.3%) relapsed and were subsequently classified as inflammatory bowel disease: 54% ulcerative colitis, 33% Crohn's disease and 13% chronic unclassified colitis. Forty-two (47.7%) did not relapse and were considered to have acute non specific colitis. The mean age at onset was significantly lower in patients with inflammatory bowel disease (32.3 years) than in patients with acute non specific colitis (42.6 years) (P < 0.001). No clinical data (diarrhea, abdominal pain, bloody stool, mucus discharge fever, weight loss) was predictive of the final diagnosis. In this series, 52.3% of patients initially classified as having an acute unclassified colitis had a final diagnosis of inflammatory bowel disease after a 2.5-3 years follow-up. These data warrant a thorough follow up of acute unclassified colitis, especially when it occurs in patients < 40 years.

Acute Disease↗

PubMed1987

Sigmoid intramural pH for prediction of ischemic colitis during aortic surgery. A comparison with risk factors and inferior mesenteric artery stump pressures.

We compared intramural pH (pHI) measured through a silicone balloon placed in the lumen of the sigmoid colon with risk factor analysis and inferior mesenteric artery (IMA) stump pressures as predictors of ischemic colitis in 34 patients undergoing elective or emergency operations on the abdominal aorta. All patients had preoperative and postoperative flexible sigmoidoscopy, IMA stump pressure measurements, and serial measurements of pHI. Logistic regression analysis showed that aortic aneurysm, age, and stenosis of the superior mesenteric artery were the only risk factors that bore a statistical relationship to ischemic colitis. Ligation of a patent IMA did not increase the likelihood of ischemic colitis. The IMA stump pressure criteria for predicting ischemic colitis were absent in nine of the ten patients in whom ischemic colitis developed and were present in five of the 24 in whom it did not develop. Intraoperative pHI dropped below 6.86 in all three patients in whom severe ischemic colitis developed. Mild colitis developed in seven patients whose minimum pH was 6.99 +/- 0.12 (mean +/- SD). No colitis developed in the remaining 24, whose minimum pH was 7.21 +/- 0.13. Thus, stump pressure is not a reliable means of predicting ischemic colitis. Aortic aneurysm, age, and superior mesenteric artery stenosis were significant risk factors. The average minimum intraoperative pHI and its duration were the best predictors for the development of ischemic colitis.

Adult↗

PubMed2004

Transdermal nicotine for induction of remission in ulcerative colitis.

BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers. Intermittent smokers often experience improvement in their symptoms while smoking. Nonsmokers with ulcerative colitis who begin smoking may go into remission. Randomized controlled trials were developed to test the efficacy of transdermal nicotine for the induction of remission in ulcerative colitis. OBJECTIVES: (1) To determine the efficacy of transdermal nicotine for induction of remission in ulcerative colitis. (2) To assess adverse events associated with transdermal nicotine therapy for ulcerative colitis SEARCH STRATEGY: The MEDLINE (via PubMed) and EMBASE databases were searched using the search criteria "ulcerative colitis" and "transdermal nicotine" or "nicotine" to identify relevant papers published between 1970 and December 2003. Manual searches of reference lists from potentially relevant papers were performed to identify additional studies. Abstracts from major gastroenterological meetings were searched to identify research submitted in abstract form only. The Cochrane Central Register of Controlled Trials and the Cochrane Inflammatory Bowel Disease Group Specialized Trials Register were also searched. SELECTION CRITERIA: We included only randomized controlled trials in which patients with active mild to moderate ulcerative colitis were randomly allocated to receive transdermal nicotine (15 to 25 mg/day) or a placebo or another treatment (corticosteroids or mesalamine). DATA COLLECTION AND ANALYSIS: Data extraction and assessment of the methodological quality of each trial were independently performed by each author. Any disagreement among reviewers was resolved by consensus. The primary outcome measure was the number of patients achieving clinical or sigmoidoscopic remission as defined by the primary studies (e.g. no symptoms of ulcerative colitis), and expressed as a percentage of the patients randomized (intention to treat analysis). Secondary outcomes included clinical response, adverse events and withdrawal because of adverse events. MAIN RESULTS: Seven studies were identified, five of which met the inclusion criteria. A meta-analysis of two trials in which 71 patients were randomized to nicotine and 70 to placebo showed a statistically significant benefit for nicotine treatment. After four to six weeks of treatment 19 of 71 patients treated with transdermal nicotine were in clinical remission compared to 9 of 70 treated with placebo (OR=2.56, 95% CI 1.02-6.45). In the same group of patients improvement or remission was noted in 29 of the 71 patients assigned to nicotine compared to 14 of 70 patients assigned to placebo (OR=2.72, 95% CI 1.28 - 5.81). For patients with left sided colitis the odds ratio was 2.31 (95% CI 1.05-5.10). When transdermal nicotine was compared to standard medical therapy no significant benefit for nicotine was observed. After four to six weeks of standard therapy (oral prednisone or mesalamine), 34 of 63 patients were in clinical or sigmoidoscopic remission compared to 33 of 66 patients treated with transdermal nicotine (OR=0.77, 95% CI 0.37-1.60). A meta-analysis of all five studies which included 137 patients treated with transdermal nicotine and 133 patients treated with a placebo or standard therapy demonstrated no statistically significant benefit of nicotine therapy (OR=1.23; 95% CI 0.71-2.14). Patients treated with transdermal nicotine were significantly more likely to withdrawal due to adverse events than patients treated with placebo or standard medical therapy (OR=5.82, 95% CI, 1.66 - 20.47) and were significantly more likely to suffer from an adverse event than patients treated with placebo or standard medical therapy (OR=3.54, 95% CI, 2.07 - 6.08). REVIEWERS' CONCLUSIONS: The results of this review provide evidence that transdermal nicotine is superior to placebo for the induction of remission in patient's with ulcerative colitis. The review did not identify any significant advantage for transdermal nicotine therapy compared to standard medical therapy. Adverse events associated with transdermal nicotine are significant and limit its use in some patients.

Administration, Cutaneous↗

PubMed2004

Colitis in patients with breast carcinoma treated with taxane-based chemotherapy.

BACKGROUND: Colitis is a rare but serious gastrointestinal complication associated with taxane-based chemotherapy in patients with cancer. The incidence, clinical presentation, and outcome of colitis in patients with breast carcinoma treated with taxane-based chemotherapy is not known. METHODS: The authors searched their electronic database and identified patients with breast carcinoma who were treated with taxane-based chemotherapy between January 1997 and December 1999. Patients diagnosed with colitis were identified and their presentation and clinical outcomes were analyzed. RESULTS: During the study period, 1350 patients received taxane-based chemotherapy. Sixty-four patients were admitted to The University of Texas M. D. Anderson Cancer Center (Houston, TX) (73 admissions) for gastrointestinal complications. Neutropenia and/or fever accounted for 56 of these admissions. Fourteen patients (16 admissions) were diagnosed with colitis. All had abdominal pain at median Day 6 of their chemotherapy cycle (range, 3-8 days), with or without other symptoms. Computed tomography scans of the abdomen and pelvis were abnormal for the 10 patients tested, whereas only 3 of the 9 patients who underwent radiographic abdominal series had abnormal findings. Two patients had a colonoscopy that confirmed the diagnosis of colitis. Blood cultures were positive in only 3 (20%) of 15 colitis events. All eight patients tested for Clostridium difficile toxin were negative. One patient died of sepsis. An autopsy subsequently revealed cecal ulceration. Two patients had bowel perforations requiring hemicolectomy. Colitis recurred in two patients after they resumed taxane-based chemotherapy without dose reduction. Dose reductions prevented the recurrence of colitis in seven patients. Treatment discontinuation of taxane-based chemotherapy also prevented disease recurrence. CONCLUSIONS: Acute abdominal pain in patients with breast carcinoma treated with taxane-based chemotherapy signaled a potentially fatal colitis, and warrants aggressive supportive care. Dose reduction or discontinuation of taxane-based chemotherapy may prevent the recurrence of colitis.

Antineoplastic Agents, Phytogenic↗

PubMed2006

DX5+ NKT cells induce the death of colitis-associated cells: involvement of programmed death ligand-1.

NKT cells are activated by CD1d and show an immune regulating function. Here, we investigated whether DX5+ NKT cells could be used to reduce colitis in a chronic colitis mouse model and studied the potential immunological mechanisms involved. Chronic colitis was induced either by transfer of enriched CD62L+ CD4+ T cells to severe-combined-immunodeficient mice or by feeding dextran sodium sulfate to immune competent mice. DX5+ NKT cells were transferred to mice with chronic colitis. Co-transfer of DX5+ NKT cells, but not CD8+ control cells, prevented the onset of colitis, and the immune regulatory effect of DX5+ NKT cells was completely abrogated by injecting CD1d blocking antibody. Moreover, DX5+ NKT cells reduced established colitis in both chronic colitis models. In vitro, DX5+ NKT cells induced cell death of colon-infiltrating lymphocytes isolated from diseased mice. This effect was inhibited in the presence of either anti-CD1d or anti-programmed death ligand-1 (PD-L1) blocking antibodies. The specific potency of DX5+ NKT cells in regulating chronic colitis in two mouse models is demonstrated. In vitro testing suggests that DX5+ NKT cells activated by CD1d induce cell death of colitis-inducing lymphocytes, which is mediated through PD-L1. Therefore, DX5+ NKT cells could be important in the regulation of immune responses associated with chronic colitis.

Adoptive Transfer↗

PubMedDate not supplied

Reticuloendothelial system Fc receptor-mediated clearance of IgG-tagged erythrocytes from the circulation of patients with idiopathic ulcerative colitis and chronic liver disease.

Immune complexes may be important in the pathogenesis of the liver disease associated with idiopathic ulcerative colitis. In the present study, we documented Fc receptor-mediated clearance by the reticuloendothelial system of immune complex-like material from the systemic circulation of 25 healthy control subjects, 19 patients with ulcerative colitis alone, 9 patients with ulcerative colitis and elevated liver enzyme tests and 8 patients with various other forms of chronic liver disease. Following an intravenous infusion of IgG-tagged 51Cr-labeled autologous erythrocytes, serial blood samples were drawn over a 2-hr period of time, and computer-generated clearance curves were obtained. The time required for clearance of 50% of infused erythrocytes (T1/2) was then calculated. Serum immunoglobulin (IgA, IgG and IgM), complement (C3 and C4) and immune complex-like activity (IgG and IgM types) were also determined. Sixteen of 19 (84%) ulcerative colitis patients and 7 of 8 (88%) chronic liver disease patients had normal clearance T1/2's (when compared to 25 healthy controls). Conversely, only 1 of 9 (11%) ulcerative colitis + chronic liver disease patients demonstrated normal clearance function. Aside from serum IgM levels, the results of serum immunoglobulin, complement and immune complex-like determinations were similar in ulcerative colitis and ulcerative colitis + chronic liver disease patients. Serum IgM levels, however, were significantly decreased in ulcerative colitis patients and increased in ulcerative colitis + chronic liver disease patients (p less than 0.001). The results indicate that the reticuloendothelial system of patients with ulcerative colitis and chronic liver disease is impaired in its ability to dear immune complex-like material from the systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1999

L-glutamine enemas attenuate mucosal injury in experimental colitis.

PURPOSE: The aim of this study was to investigate the role of 1-glutamine, short chain fatty acid, prednisolone, and mesalazine (5-aminosalicylic acid) enemas on mucosal damage and inflammation in experimental colitis. METHODS: Colitis was induced in rats with trinitrobenzene sulfonic acid in ethanol. Saline (n = 14), prednisolone (n = 13), 5-aminosalicylic acid (n = 14), 1-glutamine (n = 14), and short chain fatty acid (n = 13) enemas were applied twice daily to the rats for seven days after the induction of colitis. The sham group (n = 9) received only saline enemas. Rats were killed at the seventh day and their colonic macroscopic inflammatory scores were determined. Colonic mucosal gamma glutamyl transpeptidase activity and colonic mucosal malondialdehyde levels were measured. The same measurements but no enemas were done in the control group (n = 7). RESULTS: There were significant differences in macroscopic inflammatory scores between sham and colitis groups (P < 0.001). The macroscopic inflammatory scores of the colitis group were higher than the short chain fatty acid and glutamine groups (P < 0.05). Whereas the mucosal gamma glutamyl transpeptidase activity was diminished in prednisolone, 5-aminosalicylic acid, and short chain fatty acid groups when compared with the control group; in the colitis, sham, and glutamine groups the activity of this enzyme did not change. The mucosal malondialdehyde levels were significantly lower in the prednisolone and glutamine groups than in the colitis group. CONCLUSION: Only one of four agents tested, namely, 1-glutamine enemas, could decrease the severity of colitis both morphologically and biochemically. Moreover, L-glutamine prevented the colitis-induced oxidant injury in the colonic mucosa. On the other hand, prednisolone and short chain fatty acids seemed to improve only the physiologic changes of colitis.

Animals↗

PubMed1996

Quantification of distinct molecular species of platelet activating factor in ulcerative colitis.

The aim of this study was to characterize the synthesis and metabolism of platelet activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) by colonic mucosa from patients with ulcerative colitis and healthy individuals. Tissue was obtained by endoscopic biopsy and by scraping the mucosa from surgical resections. Tissue was assayed for the various molecular species of PAF and its biologically inactive metabolite lyso-PAF using gas chromatography/mass spectrometry. Mucosa from surgical resections for ulcerative colitis contained C16:0 PAF (mean = 156 ng/g of mucosa), but not C18:0 PAF, PAF was not identified in mucosa from normal surgical resections or in endoscopic biopsies from either patients with ulcerative colitis or normal individuals. Both C16:0 lyso-PAF and C18:0 lyso-PAF were found in mucosa from normal and ulcerative colitis surgical resections and in endoscopic biopsies from ulcerative colitis and normal tissue. Levels of lyso-PAF were similar in ulcerative colitis and normal mucosa. Incubation of mucosa from areas of active inflammation in ulcerative colitis with the calcium ionophore A23187 increased the levels of C16:0 PAF by 2-3 fold and also increased the levels of C16:0 lyso-PAF. Addition of 3H-PAF to endoscopic biopsies from either normal individuals or patients with ulcerative colitis resulted in hydrolysis to 3H-lyso-PAF. The data on colonic mucosal levels of PAF are consistent with the results of earlier studies measuring PAF in patients with ulcerative colitis by bioassay. This study examines the synthesis and metabolism of specific molecular species of PAF in ulcerative colitis for the first time.

Adult↗

PubMed2004

A high degree of aneuploidy, loss of p53 gene, and low soluble p53 protein serum levels are detected in ulcerative colitis patients.

PURPOSE: The causes for the increased risk of colorectal cancer associated with ulcerative colitis have not been fully defined. Colonic tissue of ulcerative colitis patients was examined for changes in chromosome-17-centromere copy number, loss of the p53 gene, and alterations in serum levels of the 53-kDa protein. This study was performed under the assumption that these molecular events correlate with ulcerative colitis status and duration. METHODS: Ulcerative colitis patients (n = 42) and healthy controls (n = 37) participated in the study. All participants were histopathologically and medically diagnosed. The stage of ulcerative colitis patients was stratified according to increasing risk factors for the development of colorectal cancer: left-sided colitis, pancolitis, sclerosing cholangitis, and dysplasia-associated lesions or masses. Changes in centromere number of chromosome 17 alone or in association with changes in copy number of the p53 gene were analyzed in colon tissue biopsies by fluorescence in situ hybridization. Serum p53 level was determined in blood samples by immunoprecipitation followed by separation using high-pressure liquid chromatography. RESULTS: Changes in chromosome 17 and p53 copy number and lower levels of serum p53 protein in ulcerative colitis patients directly correlated with colorectal cancer risk factors. All values significantly differed from controls. Significant direct correlations were obtained for ulcerative colitis disease duration, levels of p53 in the serum, and extent of aneuploidy. CONCLUSIONS: We demonstrate that in the colonic mucosa of ulcerative colitis patients, high levels of genomic instability, changes in p53 gene copy number, and lower levels of p53 in the serum directly correlate with the extent of disease duration and increased risk factors for colorectal cancer. Any of the measurements described herein can provide an acceptable prognostic tool in the assessment of colorectal cancer risk in ulcerative colitis patients.

Adult↗

PubMed2003

Platelet-activating factor, a critical mediator in the pathogenesis of dextran sulfate sodium-induced colitis in rats.

PURPOSE: Disorder of mucosal immunity based on an imbalance between proinflammatory and anti-inflammatory cytokines is believed to be a major factor in the pathogenesis of ulcerative colitis. Platelet-activating factor potentially stimulates the production of proinflammatory cytokines and recruits inflammatory cells. The aim of this study was to determine whether and to what extent platelet-activating factor plays a role in the pathogenesis of ulcerative colitis. METHODS: Using dextran sulfate sodium-induced colitis in rats as a model of ulcerative colitis, we analyzed the composition of cellular infiltrates and the local tissue expression of messenger ribonucleic acid for cytokine-induced neutrophil chemoattractant and tumor necrosis factor-alpha. To directly assess the impact of platelet-activating factor on the development of colitis, we also determined the efficacy of a specific platelet-activating factor receptor antagonist for preventing dextran sulfate sodium-induced colitis. RESULTS: The activity of colitis was well correlated with the upregulation of cytokine-induced neutrophil chemoattractant and tumor necrosis factor-alpha messenger ribonucleic acid in local tissues and infiltration of cytokine-induced neutrophil chemoattractant-positive neutrophils and ED1-positive macrophages. The platelet-activating factor receptor antagonist effectively ameliorated colitis, along with causing a decrease in the tissue cytokine-induced neutrophil chemoattractant messenger ribonucleic acid level and a decline in neutrophil and macrophage infiltration. However, the antagonist did not alter tissue levels of tumor necrosis factor-alpha messenger ribonucleic acid. CONCLUSION: Platelet-activating factor plays a critical role in the pathogenesis of dextran sulfate sodium-induced colitis through recruitment of cytokine-induced neutrophil chemoattractant-positive neutrophils and macrophages and/or stimulation of cytokine-induced neutrophil chemoattractant release from activated neutrophils. The tissue level of tumor necrosis factor-alpha messenger ribonucleic acid does not closely reflect the activity of colitis.

Analysis of Variance↗

PubMed1992

Frequency and significance of chronic ulcerative colitis in severe corticosteroid-treated autoimmune hepatitis.

To assess the prevalence and significance of chronic ulcerative colitis in patients with severe autoimmune hepatitis and to determine the frequency of cholangiographic and histologic features of primary sclerosing cholangitis in those with colitis, 105 patients who had been screened by annual proctoscopic examination were studied. Patients with features of colitis were compared to counterparts without colitis who had been matched by age, sex, disease severity and treatment regimen. Seventeen patients (16%) had findings of chronic ulcerative colitis. Twelve of these underwent cholangiography and five (42%) had features of primary sclerosing cholangitis. Patients with and without cholangiographic abnormalities were indistinguishable by clinical, laboratory, immunoserologic, and histologic features. Fibrous obliterative cholangitis was present in only two patients, including one with normal cholangiography. Patients with colitis entered remission less frequently (59 vs. 94%, p less than 0.05), failed treatment more commonly (41 vs. 6%, p less than 0.05) and progressed to cirrhosis more frequently (75 vs. 25%, p less than 0.05) than counterparts without colitis. Patients with colitis but normal cholangiography, however, responded satisfactorily to therapy. We conclude that chronic ulcerative colitis can coexist with severe autoimmune hepatitis in the absence of primary sclerosing cholangitis or hepatitis C infection. Under such circumstances its presence does not adversely influence treatment outcome. Primary sclerosing cholangitis cannot be excluded by routine examinations and its presence is associated with a poor treatment response. Cholangiography should be considered in all patients with autoimmune hepatitis and colitis, especially in those recalcitrant to therapy.

Adult↗

PubMed2005

Luminal and parenteral TFF2 and TFF3 dimer and monomer in two models of experimental colitis in the rat.

BACKGROUND: Peptides of the trefoil factor family (TFF1, TFF2 and TFF3) are cosecreted with mucus from mucus-producing cells in most organ systems and are believed to interact with mucus to form high-viscosity stable gel complexes. In the gastrointestinal tract, they sustain the mucosal barrier, and both injected and orally administered TFF peptide have protective and healing functions in the gastric mucosa. AIM: To investigate the possible treatment effect of luminally and parenterally administered TFF peptides in experimental colitis in rats. METHODS: Colitis was induced by administration of 5% dextran sodium sulphate in the drinking water or by one intraperitoneal injection of mitomycin C, 3.75 mg/kg. TFF peptides were administered as subcutaneous injections or directly into the lumen via a catheter placed in the proximal colon. Treatments were saline, TFF2, TFF3 monomer or TFF3 dimer 5 mg/kg twice per day throughout the study [dextran sulphate sodium (DSS)] or from day 4 to 7 (mitomycin C). Colitis severity was scored in a stereomicroscope and histologically. RESULTS: Luminal treatment with TFF3 in its dimeric form significantly improved the colitis score in both colitis models, whereas TFF2 had positive effect only in DSS-induced colitis. The TFF3 monomer was without any effects in both models. Treatment effect was most pronounced in the middle part of the colon, closest to the tip of the catheter. Injected TFF peptides, especially the TFF3 monomer, aggravated the colitis score in both colitis models. CONCLUSIONS: Intracolonic administration of TFF3 dimer and TFF2 improves experimentally induced colitis in rats. The TFF3 monomer has no effect. Parenteral administration of TFF peptides aggravates the colitis especially the TFF3 monomer.

Animals↗