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PubMed1991

Ulcerative colitis disease activity as subjectively assessed by patient-completed questionnaires following orthotopic liver transplantation for sclerosing cholangitis.

To assess whether or not liver transplantation and subsequent immunosuppression with cyclosporine and prednisone affect ulcerative colitis symptomatology, we surveyed by questionnaire all 23 surviving patients with pretransplant colonoscopy-documented ulcerative colitis who were transplanted for primary sclerosing cholangitis between June 1982 and September 1985. At follow-up [89.8 +/- 7.6 weeks (mean +/- SEM], all six patients who had had asymptomatic colonoscopy-documented ulcerative colitis reported continued ulcerative colitis quiescence. Among the 17 patients who had had symptomatic colonoscopy-documented ulcerative colitis at time of liver transplantation, 88.2% reported improvement in overall ulcerative colitis severity (P less than 0.001), with significant improvement in the frequency of bowel movements reported by 100%, in crampy abdominal pain by 87.5%, in bowel urgency by 75%, in the occurrence of pus or mucus in stool by 87.5%, in the incidence of ulcerative colitis flares by 81.8%, and in the number of days unable to function normally due to ulcerative colitis symptoms by 78.6% (all at least P less than 0.01). These data demonstrate that ulcerative colitis symptom severity significantly improves following liver transplantation with immunosuppression with cyclosporine and prednisone.

Adult↗
PubMed1991

Inflammatory mediators in cotton-top tamarins (CTT) with acute and chronic colitis.

Spontaneous colitis in CTT's presents cytological characteristics similar to chronic ulcerative colitis in humans, e.g. inflammatory cell infiltrate and crypt abscesses. To better characterize CTT colitis as a potential model for human inflammatory bowel disease (IBD), inflammatory mediators identified in colonic tissue of human IBD patients and/or experimental colitis models were assayed. Inflammatory mediator changes in plasma and colon from tamarins with acute (n = 10) and chronic (n = 10) colitis (by mucosal biopsy) were assayed by RIAs. Similar inflammatory mediators were found in the CTT's with acute colitis. In the plasma, PAF and PGE2 levels were lower in acute colitis CTT's, no LTB4 was detected, and histamine levels were not different from chronic colitic animals. In the colon, myeloperoxidase and interleukin-1 beta were significantly higher in acute colitis, PGE2 and LTB4 were higher but not significantly, and PAF was not different from chronic CTT's. These data suggest that a combination of events are occurring in the pathogenesis of tamarin colitis that involves some of the same mediators that are found in the human disease and in other experimental models. The importance of these findings to human IBD remains for further investigation; however, the spontaneous primate model offers an exciting approximation of the disease development and merits further investigation for understanding the pathogenesis of human IBD as well as to aid in development of targeted therapeutics.

Acute Disease↗
PubMed1995

Changes in substance P-immunoreactive innervation of human colon associated with ulcerative colitis.

The amount of colonic substance P and substance P-receptors is increased in ulcerative colitis, which may denote that substance-P is involved as a neurogenic mediator in the inflammatory process of ulcerative colitis. We studied the anatomical distribution of elevated colonic substance P in ulcerative colitis and assessed morphometrically whether the changes in substance P correlate with alterations in colonic innervation. Full-thickness specimens of colonic wall were obtained from normal human colons (N = 9) and the most and least affected regions of ulcerative colitis colons (N = 10) and immunostained for substance P. Substance P immunoreactivity index was calculated by multiplying each intensity value by the number of pixels exhibiting this intensity value. The numbers of substance P-immunoreactive nerve fibers in the lamina propria were markedly increased, and their fluorescence intensity was enhanced in ulcerative colitis. The longitudinal muscle layer contained substance P-immunoreactive nerve fibers in ulcerative colitis, but not in the controls. The substance P-immunoreactive index (= number x intensity of nerve fibers) was 3.42 +/- 1.49 in controls, 21.19 +/- 7.79 in mild ulcerative colitis regions (P < 0.05), and 29.68 +/- 9.81 in severe ulcerative colitis regions (P < 0.01). Increase in the number of substance P nerve fibers is in accordance with the hypothesis that substance P contributes to neurogenic mediation of inflammation in ulcerative colitis.

Aged↗
PubMed2005

Rapamycin decreases leukocyte migration in vivo and effectively reduces experimentally induced chronic colitis.

BACKGROUND: Immunosuppressive calcineurin inhibitors, like cyclosporine (CsA), can be used for the clinical management of severe ulcerative colitis. However, patients treated with CsA are at a risk for developing kidney failure and may be more susceptible to colon cancer. Furthermore, severe neurotoxicity and hypertension are common problems. To avoid the side effects of CsA, new immunosuppressive drugs to treat colitis are needed. The aim of the present study was to test the immunosuppressive mammalian target of rapamycin inhibitor rapamycin in an experimental model of chronic colitis and to compare its effectiveness with CsA. METHODS: Chronic colitis was established in Balb/c mice after four feeding cycles of dextran sodium sulfate. Because leukocyte recruitment to sites of intestinal inflammation is crucial for the development of chronic colitis, intravital microscopy was used to study the effect of rapamycin and CsA on leukocyte-endothelium interactions and leukocyte extravasation. To assess the degree of colitis, histological sections were evaluated. RESULTS: Both rapamycin and cyclosporine effectively reduced leukocyte sticking (>60%) in submucosal venules, as compared to controls. Furthermore, rapamycin, but not CsA, reduced (>35%) leukocyte extravasation in the mucosa. Both rapamycin and CsA treatments significantly improved the histologic inflammation score. CONCLUSION: Our in vivo results demonstrate that rapamycin reduces leukocyte sticking and extravasation during chronic colitis induction and proves to be as effective as CsA at reducing experimental chronic colitis. These results support the use of rapamycin in clinical trials to avoid serious side effects of CsA therapy in chronic colitis patients.

Animals↗
PubMed2001

Clinical and histopathological features of dextran sulfate sodium induced acute and chronic colitis associated with dysplasia in rats.

We examined the clinical and histopathological features of the dextran sulfate sodium (DSS) induced acute and chronic colitis in rats as a model for studying basic biology of the inflamed colonic mucosa. Acute colitis was induced in male Wistar rats by 4 days (AI) or 7 days (AII) of oral 5% (wt/vol) DSS (mol. wt. 54,000) in their drinking water. Chronic colitis was induced in 8 experimental groups: CI=7 days DSS followed by 10 days water (=one cycle); CII=two cycles; CIII to CVIII (three to eight cycles) received only 4 days 5% DSS followed by 10 days drinking water. The entire colons were examined histologically; dysplasia was graded as: indefinite/probably negative for dysplasia, indefinite/probably positive for dysplasia, low-grade dysplasia, or high-grade dysplasia. The earliest clinical findings in the acute colitis group over 4 days occurred on day 2 (hemoccult positive stools, loose stools or diarrhea and weight loss). The maximal disease activity was noted on day 7 accompanied by a 53% mortality rate. The histological inflammation scores were significantly higher on day 7 than on day 4. All rats had extensive ulcerations predominantly in the rectum and cecum. The number of rats having ulcerations was markedly lower in the chronic colitis groups. The majority (75%) of the crypt lesions suspicious for dysplasia were classified as mucosa indefinite/probably negative for dysplasia. We classified 18 crypt lesions as low-grade dysplasia and one lesion as high-grade dysplasia (after eight cycles). No invasive carcinoma was observed. Most low-grade dysplasias (83%) occurred after five cycles of DSS/water, located mostly in the rectum (44%) and colon transversum (33%). Our findings suggest that the DSS colitis model in rats may be an interesting model for studying the sequence chronic inflammation-dysplasia in human ulcerative colitis. Further long-term studies with the present DSS colitis model in rats might also prove it as a reliable model to study the sequence high-grade dysplasia and colitis associated-cancer.

Acute Disease↗
PubMed2004

Female infertility after ileal pouch-anal anastomosis for ulcerative colitis.

PURPOSE: Although ulcerative colitis commonly affects young females, the impact of ulcerative colitis and its treatment on female fertility have not been well studied. The purpose of this survey was to examine the impact of ulcerative colitis and ileal pouch-anal anastomosis on female reproductive ability. METHODS: Demographic, reproductive history, and disease history information were obtained via a questionnaire mailed to females who had pelvic pouch surgery or nonoperative management for ulcerative colitis. Based on age at diagnosis, age at surgery, and marital status, 153 females who had pelvic pouch surgery and 60 females who had nonoperative management for ulcerative colitis were identified for inclusion. Patients were asked if they attempted to become pregnant, when relative to their diagnosis or surgery, and if they were successful. Married or cohabiting females aged 18 to 44 years who failed to become pregnant during 12 months of unprotected intercourse were defined as infertile. RESULTS: The infertility rate was significantly higher in females who had pelvic pouch surgery compared with females managed nonoperatively (59/153 (38.1 percent) vs. 8/60 (13.3 percent), respectively; P < 0.001). There was no difference in female fertility after diagnosis with ulcerative colitis compared with before diagnosis (odds ratio, 0.68; P = 0.23). In contrast, there was a 98 percent reduction in fertility after pelvic pouch surgery compared with before surgery (odds ratio, 0.021; P < 0.0001). By logistic regression, increasing age was the only factor associated with failure to become pregnant after surgery (odds ratio, 1.136 per additional year of age; P = 0.027). CONCLUSIONS: Females with ulcerative colitis who are managed nonoperatively have normal fertility, which suggests that ulcerative colitis and medical therapy do not decrease female reproductive ability. After pelvic pouch surgery for ulcerative colitis, female fertility is significantly decreased and this problem should be discussed routinely with patients considering this procedure.

Adolescent↗
PubMed2003

Characterization and clinical behavior of Crohn's disease initially presenting predominantly as colitis.

PURPOSE: We studied patients with Crohn's disease affecting the colon to characterize disease behavior and to determine whether such patients might be candidates for sphincter-sparing surgery. METHODS: Ninety-two consecutive patients with Crohn's colitis were studied prospectively. Mean follow-up after diagnosis was 82 (range, 6-291) months. Parameters that were evaluated included previous surgery for Crohn's disease, granulomatous vs. nongranulomatous disease, extent of colonic involvement, and presence or absence of extracolonic disease. The clinical course of the disease and postoperative outcome were evaluated. The outcome of Crohn's colitis patients who underwent ileal pouch-anal anastomosis for presumed ulcerative colitis was also evaluated. RESULTS: There were 39 patients with granulomatous colitis and 53 patients without granulomas. There was no statistical difference in the age of diagnosis or presence of small-bowel (23 vs. 27 percent), ileocolic (34 vs. 30 percent), or perineal (36 vs. 22 percent) disease in these patients. At initial presentation, 88 percent of patients with pancolitis had colitis alone without other sites of intestinal disease compared with only 37 percent of patients with segmental colitis (P < 0.001). Kaplan-Meier analysis showed that patients with granulomas and patients with segmental colitis at presentation have a significantly higher recurrence when compared with patients without granulomas and patients with pancolitis (P < 0.03). Thirteen patients without granulomatous disease and eight with granuloma underwent ileal pouch-anal anastomosis. Seven patients (3 with granuloma, 4 without granuloma) had a recurrence of Crohn's disease in the ileal pouch; 2 required pouch removal and permanent diversion for fistulizing disease in the ileal pouch and 5 were successfully treated conservatively without surgery. CONCLUSION: The presence of granulomas and segmental involvement of the colon in patients with Crohn's colitis may reflect a more virulent clinical course. Ileal pouch-anal anastomosis may be considered as an option in select patients with Crohn's colitis without small-bowel or perianal disease. Based on our data, patients with nongranulomatous pancolitis may be better candidates for sphincter-sparing surgery.

Adolescent↗
PubMed2006

A comparison of adverse events and functional outcomes after restorative proctocolectomy for familial adenomatous polyposis and ulcerative colitis.

PURPOSE: Restorative proctocolectomy is the procedure of choice for patients undergoing proctocolectomy for familial adenomatous polyposis or ulcerative colitis. This meta-analysis was designed to identify differences in adverse events and functional outcomes between these two groups. METHODS: Studies published between 1986 and 2003 that compared outcomes between patients with familial adenomatous polyposis and ulcerative colitis were included. Meta-analytical techniques using random effect models were used to compare short-term and long-term adverse events as well as functional outcomes between the groups. RESULTS: Nineteen studies comprising 5,199 patients (familial adenomatous polyposis, 782; ulcerative colitis, 4,417) were analyzed. There were no significant differences in immediate postoperative adverse events between the two groups. Pouch-related fistulation was significantly increased in the ulcerative colitis group (10.5 percent vs. familial adenomatous polyposis 4.8 percent; odds ratio 2.31; P < 0.001). There was no significant difference in pouch failure between the two groups (ulcerative colitis 5.8 percent vs. familial adenomatous polyposis 4.5 percent; odds ratio 1.22; P = 0.43). The incidence of pouchitis was significantly greater in the ulcerative colitis group (30.1 vs. 5.5 percent; odds ratio 6.44; P < 0.001). Patients with familial adenomatous polyposis had a significant advantage in stool frequency with one less motion per 24 hours (95 percent confidence interval, 0.21-1.76; P = 0.01). CONCLUSIONS: In contrast to studies reporting similar outcomes for patients undergoing restorative proctocolectomy for familial adenomatous polyposis or ulcerative colitis, the present meta-analysis suggested that patients with ulcerative colitis are at greater risk of pouch-related fistulation and pouchitis. Although there was an increase in the 24-hour stool frequency in the ulcerative colitis group, this may be accounted for by the younger age at surgery in the familial adenomatous polyposis group.

Adenomatous Polyposis Coli↗
PubMed1991

Colonic motor activity in acute colitis in conscious dogs.

The changes in motor activity of the colon during acute colitis were investigated in six conscious dogs. The motor activity was recorded with seven strain-gauge transducers. Colitis was induced in the entire colon by luminal perfusion of acetic acid. The dogs exhibited urgency and diarrhea with mucus and blood during colitis. The mucosa was diffusely erythematous and friable and there were scattered ulcerations over the mucosal surface. The motor activity of the colon changed in several ways during colitis: (a) the total duration per hour and the mean duration of contractile states decreased significantly; (b) the cycle length of colonic migrating motor complexes was significantly prolonged, and the nonmigrating motor complexes were almost completely absent; and (d) the incidence of giant migrating contractions increased significantly. About half of the giant migrating contractions were followed by defecation. The remaining expelled mucus or gas. Sometimes, a migrating motor complex in the colon was also followed by defecation; this was never observed in the normal state. The motor activity of the colon was still decreased and the cycle length prolonged 21 days after induction of colitis. However, the dogs were asymptomatic at this time and the mucosa looked normal at colonoscopy. The incidence of giant migrating contractions was also normal at this time. It was concluded that the dog is a good model for the study of colitis because of the similarity of symptoms with human ulcerative colitis. The phasic contractions of the colon decreases during colitis but the incidence of giant migrating contractions is increased. The diarrhea in colitis may primarily be due to the large number of giant migrating contractions in the middle and the distal colon.

Acute Disease↗
PubMed1993

On the specificity of altered muscle function in experimental colitis in rats.

BACKGROUND: Studies on muscle contraction in colitis yield conflicting data that may reflect differences in the manner in which colitis is induced. Therefore, we compared distal colonic longitudinal muscle contraction in four models of colitis in the rat. METHODS: Distal colitis was induced by intrarectal administration of trinitrobenzene sulfonic, acetic acid, or Trichinella spiralis larvae, or by intraperitoneal injection of mitomycin C. Colonic myeloperoxidase activity was used to monitor acute inflammation. RESULTS: Myeloperoxidase activity increased in each model of colitis. In trinitrobenzene-treated rats, contractile responses to carbachol, substance P, and KCl decreased by 64%, 76%, and 58%, respectively. In acetic acid treated rats, responses induced by carbachol, substance P, or KCl were each significantly decreased by 73%, 68%, and 55% and were similarly reduced by 42%, 77%, and 46%, respectively, in rats with T. spiralis colitis. In mitomycin-induced colitis, these respective responses also decreased significantly by 71%, 55%, and 54%. CONCLUSION: Decreased contractility of longitudinal muscle in acute colitis in rats is independent of the manner in which the colitis is induced and is mediated at a receptor-independent locus on the muscle cell.

Acetates↗
PubMed2005

Amelioration of experimental colitis by Copaxone is associated with class-II-restricted CD4 immune blocking.

UNLABELLED: Copaxone modifies TH1 immune response in multiple sclerosis. As Crohn's disease shares TH1 predominance, this study came to investigate the anti-inflammatory response of Copaxone in animal model of colitis. METHODS: Colitis was induced by intra-rectal instillation of TNBS in 2 animal groups; one of them was daily treated intraperitoneally by 300 mug Copaxone starting 48 h post-colitis induction. Both colitis groups were compared to naive group. Eight male C57Bl6 mice were used in each group. At day 12, distal colon was excised for standard scoring, splenocytes were isolated for FACS and serum cytokines were assessed. Splenocytes were in-vitro-stimulated with colitis protein extracts in the presence or absence of Copaxone. Lymphocytes were blocked by either MHC anti-class I or anti-class II antibodies prior to Copaxone administration. RESULTS: Copaxone markedly alleviated macro/microscopic colitis scoring as they decreased from 2.9 +/- 1.1/2.6 +/- 0.8 in colitis group to 1.7 +/- 1/1.5 +/- 0.5 in Copaxone-treated mice (P = 0.03/P = 0.008, respectively) compared to 0 +/- 0/1 +/- 0 in naives (P < 0.001/P < 0.01, respectively). CD4 subsets significantly decreased following Copaxone administration as compared to naive mice (P = 0.05). Although Copaxone-treated mice manifested a block of both serum TH1/TH2 responses, only interferon gamma secreting CD4 cells significantly decreased. NK cells tend to increase following colitis induction (P = 0.08), however, they significantly decreased in Copaxone-treated animals (P = 0.006). NK-T followed NK pattern. Using in vitro studies, Copaxone showed amelioration of T-cell proliferation that was significantly blocked when cells were pre-incubated with anti-MHC class II but not class I antibodies. CONCLUSIONS: Copaxone had class-II-restricted anti-inflammatory effect in our animal colitis model associated with CD4/NK/NKT/TH1/TH2 suppression.

Animals↗
PubMed2001

Experimental colitis decreases rat jejunal amino acid absorption: role of capsaicin sensitive primary afferents.

Ulcerative colitis and experimental colitis are known to be associated with functional and structural abnormalities of the small intestine. The aim of this study was to determine whether experimental colitis in the rat has any effect on jejunal amino acid absorption and to investigate the neural mechanisms involved. In Sprague Dawley rats, colitis was induced by intracolonic administration of 0.1 ml of 6% iodoacetamide. Alanine absorption in the jejunum was measured using the single pass intraluminal perfusion technique in vivo and the three-compartment model in vitro. Experiments were done in normal and sham treated rats, as well as in rats that underwent neonatal capsaicin treatment, adult capsaicin treatment, or subdiaphragmatic vagotomy. Colitis was more severe in rats subjected to neonatal or adult capsaicin treatment, but was not affected by subdiaphragmatic vagotomy. In rats with colitis, jejunal alanine absorption was reduced by 2% (P>0.05), 28%, 40%, and 18% (P<0.001) at 1, 1.5, 2, and 3 days post rectal iodoacetamide administration. A rebound increase of 12% above baseline was noted at 4 days (P<0.05). Similar results were noted in vitro. In rats that received two consecutive injections of iodoacetamide, the decrease in jejunal alanine absorption occurred earlier, was more severe, and persisted for more than 30 days. Neonatal as well as adult capsaicin treatment aggravated both the colitis and the decrease in jejunal alanine absorption. On the other hand, subdiaphragmatic vagotomy attenuated the decrease in jejunal alanine absorption, but had no significant effect on colitis severity. It is concluded that iodoacetamide induced colitis impairs jejunal amino acid absorption and that this effect involves vagal efferents as well as capsaicin sensitive primary afferents.

Afferent Pathways↗
PubMedDate not supplied

Microscopic colitis: a missed diagnosis?

CONTEXT: Collagenous colitis and lymphocytic colitis, collectively designated microscopic colitis, have until recently been considered as rare gastrointestinal disorders. New data suggest, however, that these disorders are relatively common, and to reach the correct diagnosis both the gastroenterologist and the pathologist must be aware of these diagnoses when evaluating patients with persistent watery non-bloody diarrhoea. STARTING POINT: In an epidemiological study of a well-defined Swedish population, Martin Olesen and colleagues show that microscopic colitis needs to be considered as a common gastrointestinal disorder (Gut 2004; 53: 346-50). In colonic biopsy specimens from 1018 patients who had a colonoscopy because of non-bloody diarrhoea in 1993-98, 97 patients (9.5%) were found to have microscopic colitis. In about a third of these cases, the diagnosis was missed in the primary histological evaluation. Median age at diagnosis was 64 years for collagenous colitis and 59 years for lymphocytic colitis. The annual incidence of the diseases was higher than previously considered and matched the incidence of Crohn's disease, and in combination they approached the incidence of ulcerative colitis. WHERE NEXT: The high regional incidence of microscopic colitis means that both clinicians and pathologists need to be more aware of the diagnosis, especially in the elderly female population with a clinical picture of watery non-bloody diarrhoea. Because of the potentially disabling symptoms, clinicians need to develop and evaluate new therapies.

Colitis, Microscopic↗
PubMed2001

Survival and causes of death in Italian patients with ulcerative colitis. A GISC nationwide study.

BACKGROUND: Death rate for patients with ulcerative colitis has changed over last few decades. Recent studies indicate that cumulative long-term mortality is comparable to that in general population, and that deaths may depend on causes not strictly related to colonic disease. AIM: To evaluate overall and cause-specific mortality rate in a large group of Italian patients with ulcerative colitis. METHODS: A total of 2,066 ulcerative colitis patients aged >18 years consecutively diagnosed in twenty Italian Gastroenterology Units between 1964 and 1995 were followed-up from diagnosis until 1997. Standardised Mortality Ratios and Relative Survival Ratios were calculated. RESULTS: Overall mortality of patients with ulcerative colitis was comparable to that in general population with 93 deaths observed versus 92.1 expected (standardises mortality ratio, 1.0; 95% confidence interval, 0.8-1.2). Significantly higher mortality was observed in patients under 30 years of age at diagnosis (standardised mortality ratio, 2.7; 95% confidence interval, 1.3-4.9), and in those diagnosed before 1974 (standardised mortality ratio, 2.7; 95% confidence interval, 1.1-5.7). Proctocolitis and complications from surgery were mentioned in 11 and 5 certificates, respectively. A significant excess of deaths was observed for colorectal cancer (colon: standardised mortality ratio, 3.0; 95% confidence interval, 1.0-6.9; rectum: standardised mortality ratio, 4.4; 95% confidence interval, 1.2-11.3), and haemolymphopoietic neoplasms (standardised mortality ratio, 2.8; 95% confidence interval, 1.0-6.1), in particular multiple myeloma and non-Hodgkin lymphoma. A significant deficit of deaths was observed for cancer of the respiratory system (standardised mortality ratio, 0.3; 95% confidence interval, 0.1-1.0). CONCLUSIONS: This study confirms that, also in Italy, mortality of patients with ulcerative colitis is comparable to that in general population. Only 12% of deaths were due to ulcerative colitis itself, whereas 10% of deaths were attributed to colorectal cancer. Deaths from colorectal cancer occurred, on average, 9 years after diagnosis of ulcerative colitis, suggesting that the risk of cancer is not limited to patients with long-standing colitis. As to mortality for causes unrelated to colitis, there was an excess of deaths due to malignancies of the haemolymphopoietic system.

Adult↗
PubMed2004

Update on the etiology, pathogenesis and diagnosis of ulcerative colitis.

Evidence is accumulating that both genetic and environmental factors contribute to ulcerative colitis. The most consistent genetic associations have been shown for the MHC locus HLA Class II alleles, but the interleukin-1 family of genes and the multidrug resistance gene MDR1 have also been implicated as genetic susceptibility factors for the development of disease. In addition, there is a relationship between ulcerative colitis and bacterial flora, with an increased number of adherent Bacteroides spp. and Enterobacteriaceae spp. present in inflamed bowel segments. Conversely, cigarette smoking and appendectomy have both been shown to protect against the development of ulcerative colitis. Despite our improved understanding of the genetics and inflammatory mechanisms that underpin this disease, however, the etiology and pathogenesis of ulcerative colitis remain undefined. The diagnosis of ulcerative colitis is being aided by recent advances in diagnostic strategies, including the detection of fecal and serologic markers and the use of wireless capsule endoscopy, but, in the absence of a pathognomonic marker, the definition of this disease remains based on well-established clinical, endoscopic and histologic criteria. In particular, it is difficult to discriminate ulcerative colitis from other forms of colitis, including Crohn's disease, and there seems to be a growing overlap of pathophysiologic processes between ulcerative colitis and post-infectious irritable bowel syndrome. Patients who remain indeterminate between ulcerative colitis and Crohn's disease also continue to be a diagnostic challenge.

Biomarkers↗
PubMed2003

Infliximab in the treatment of medically refractory indeterminate colitis.

AIM: To examine the outcome of infliximab intervention in refractory indeterminate colitis. METHODS: Twenty patients with severe, medically refractory indeterminate colitis were treated with infliximab. All patients initially received infliximab, 5 mg/kg, intravenously and, in some patients, the dose was subsequently increased to 10 mg/kg. The number of infusions ranged from one to 16 per patient. Indeterminate colitis was defined as colitis that could not be classified with certainty as Crohn's disease or ulcerative colitis based on traditional clinical, endoscopic and histopathological criteria. The clinical response to infliximab was classified as complete response, partial response or non-response. RESULTS: Fourteen of the 20 patients (70%) showed a complete response to infliximab treatment, two showed a partial response and four showed no response. The four non-responders underwent colectomy with ileal pouch-anal anastomosis. The resected colon specimen was consistent with ulcerative colitis in all four cases, although two were subsequently re-classified as Crohn's disease. Eight additional patients were subsequently re-classified as having Crohn's disease on longer follow-up evaluation, whilst eight continued to have features of indeterminate colitis. The response rate to infliximab treatment was similar in both groups. CONCLUSIONS: Infliximab is effective in approximately two-thirds of patients with indeterminate colitis, and thus may be considered for patients with refractory disease prior to colectomy. The follow-up time afforded by infliximab treatment may allow for more accurate classification of the disease in a significant proportion of patients whose colitis has indeterminate features at initial presentation.

Adolescent↗
PubMed2002

Microscopic colitis with giant cells.

AIMS: Collagenous colitis and lymphocytic colitis are the two types of microscopic colitis with specific morphological features. In this report we describe a new histopathological subtype of microscopic colitis. METHODS AND RESULTS: Colonoscopy in four patients with chronic watery diarrhoea showed no macroscopic abnormalities. The random biopsies from the colon showed subepithelial multinucleated giant cells in combination with the features of collagenous colitis in three patients and lymphocytic colitis in one patient. These multinucleated giant cells were positive for CD68. The density of macrophages was highest in the most superficial part of the lamina propria. In one patient, a previous biopsy showed features consistent with collagenous colitis without multinucleated giant cells. Treatment with budesonide led to the disappearance of diarrhoea in all four patients. CONCLUSIONS: The clinical and histopathological features of the four presented patients indicate that there exists a histopathological subtype of microscopic colitis characterized by the presence of subepithelial multinucleated giant cells, which probably arise from fusion of subepithelial macrophages. Analysis of more patients with this histopathological subtype of microscopic colitis is necessary to determine whether they also form a clinically distinct group.

Aged↗
PubMed2004

Colitis is associated with thymic destruction attenuating CD4+25+ regulatory T cells in the periphery.

BACKGROUND & AIMS: Syngeneic bone marrow transplantation into the adult tgepsilon26 mouse results in severe wasting disease and colitis. On transplantation, the rudimentary thymus of the adult tgepsilon26 mouse repopulates briefly but quickly regresses in temporal association with the onset of colitis. The aim of this study is to test the hypothesis that treatment of colitis restores thymic capability to generate regulatory T cells (CD4+25+ T(R) cells). METHODS: Colitis was induced by bone marrow transplantation into adult irradiated tgepsilon26 mice. Colitis was prevented by 3 distinct modalities. CD4+25+ T cells were collected from both the thymus and spleen and studied for regulatory function by an in vitro suppression assay. RESULTS: CD4+25+ T(R) cells do not develop efficiently in the thymus of bone marrow transplanted adult tgepsilon26 mice, which have a developmental arrest affecting thymic epithelium. By contrast, the thymic epithelium of neonatal tgepsilon26 mice supports development of T(R) cells. Consequently, colitis develops only in adult transplanted mice but not in the neonatally transplanted mice. Treatment of colitis prevents destruction of the thymus of adult transplanted tgepsilon26 mice and T(R) cells are produced. CONCLUSIONS: The negative impact of colitis on T(R) development in the thymus, which was confirmed in a second model of colitis, has profound implications for the pathogenesis and treatment of human inflammatory bowel disease.

Animals↗