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Pancreatic changes in TNBS-induced colitis in mice.

BACKGROUND AND AIM: Recent clinical data suggest that pancreatitis could be an extraintestinal manifestation of inflammatory bowel disease. However, no experimental data support such a clinical relationship. The aim of this study was to investigate the presence of pancreatic damages in mice with TNBS-induced colitis. METHODS: Colitis was induced in Balb/C mice by intrarectal instillation of TNBS. Control mice received either intrarectal instillation of NaCl saline solution or 50% ethanol. Presence of colitis was assessed by macroscopic and microscopic examination, extent of mucosal damage being evaluated by the scoring systems of Wallace and Ameho in 8 mice with TNBS-induced colitis and in 4 controls. Pancreatic samples from the same mice underwent morphological examination after standard coloration. Intrapancreatic expression of the pancreatitis-associated protein (PAP), a marker of pancreatic inflammation, was monitored by automated immunohistochemistry using specific antibodies. In addition, quantification of TNFalpha mRNA by competitive PCR and semi-quantification of PAP, IL-10 and IL-1B mRNAs were performed on pancreas in 10 mice with TNBS-induced colitis and in 10 control mice. RESULTS: All mice treated with TNBS and none of the controls had colitis. Macroscopic and microscopic examination of the pancreas of the 4 control mice was normal, whereas in 5 out of the 8 TNBS-treated mice histological changes were observed, with inflammatory infiltrate and fibrin aggregates at the periphery of the gland. PAP immunohistochemistry was negative in all control mice and positive in all mice with TNBS-induced colitis, with a patchy distribution of staining. PAP immunolocalized to the cytoplasm of acinar cells, duct cells and islets of Langherans being negative. PAP and IL-1B mRNA levels in the pancreas were significantly increased but the increase in TNFalpha mRNA level did not reach statistical significance (P=0.06). IL-10 mRNA levels did not show any significant modification. CONCLUSION: PAP overexpression in pancreas demonstrates that inflammatory stress early occurs in the mouse pancreas during the course of TNBS-induced colitis. The concomitant pancreatic overexpression of IL-1B and, to a lesser extent, of TNFalpha, two proinflammatory cytokines also associated with the intestinal lesions of colitis, supported a pancreatic inflammatory mechanism mediated by cytokines.

Animals↗

Circulating auto-antibody against hepatoma-derived growth factor (HDGF) in patients with ulcerative colitis.

BACKGROUND/AIMS: Various circulating auto-antibodies have been reported in patients with ulcerative colitis. Hepatoma-derived growth factor (HDGF) is a mitogen, localized dominantly in the nucleus of proliferating cells. In this study, we demonstrated the circulating anti-HDGF auto-antibody and investigated its clinical roles in patients with ulcerative colitis. METHODOLOGY: Anti-HDGF IgG antibodies were measured by the enzyme-linked immunosorbent assay with recombinant HDGF in 20 healthy volunteers and 40 patients with ulcerative colitis. RESULTS: Circulating anti-HDGF antibody was detected in the serum of a patient with total colitis by Western blotting. Anti-HDGF auto-antibodies were detected at 65.6% in the serum of patients with total/left-sided colitis, compared with healthy subjects at 10%. During active stage, the circulating anti-HDGF auto-antibodies were detected at a higher frequency of 78.3% than those in remission stage at 37.5%. Furthermore, the titers during active colitis were higher than those during the remission stage. Anti-HDGF auto-antibodies were not detected in any patients with proctitis. CONCLUSIONS: These findings suggest that anti-HDGF auto-antibodies in the serum of patients with ulcerative colitis would help to classify the total/left-sided colitis from proctitis, and the serial measurement of the titer would also be a good marker for the active colitis.

Autoantibodies↗

[Expression of heme oxygenase-1 in ischemic colitis].

BACKGROUND/AIMS: Ischemic colitis is a vascular condition of inadequate blood flow in the colon which leads to colonic inflammation and can cause significant morbidity and mortality. Oxidative stress is an early initiating event in ischemia and reperfusion injury. Heme oxygenase (HO) is considered to be an antioxidant enzyme that catabolizes heme to carbon monoxide, free iron and biliverdin. The aim of this study was to evaluate the expression patterns of HO-1, inducible form of HO, in ischemic colitis. METHODS: We analyzed the twelve cases of clinically and pathologically diagnosed ischemic colitis without surgical intervention compared with normal colon (n=10) and psedomembranous colitis (n=5). Immunohistochemical stainings for HO-1 were performed in paraffin-embedded tissues. RESULTS: The age of the patients ranged from 56 to 84 years (mean: 67 years) in ischemic colitis. Eight patients (66.7%) were female. The most common presenting symptom was bloody stool (66.7%) and rectosigmoid area (91.7%) of the large intestine was the most common ischemic site. Expression of HO-1 in ischemic colitis was high in contrast to normal colonic mucosa or psedomembranous colitis. CONCLUSIONS: Ischemic colitis usually involves the rectosigmoid area in elderly female patients with a history of bloody stool. High expression of HO-1 in ischemic colitis may be responsible for a protective mechanism to ischemia or heme injury.

Aged↗

Mucosal function in rat jejunum and ileum is altered by induction of colitis.

Many studies dealing with trinitrobenzene sulfonic acid (TNBS) colitis in rats have been carried out referring only to the colon. In humans, ulcerative colitis (UC) can extend a variable distance into the terminal ileum in a phenomenon known as backwash ileitis (BWI). The aim of this study was therefore to examine the effect of TNBS-induced colitis on different aspects of the rat ileum and jejunum. We hypothesized that TNBS administration would lead to a systemic influence on the small intestine. Rats were induced colitis by administration of 0.25 ml of 2,4,6-trinitrobenzene sulfonic acid and 72 h after colitis induction animals were sacrificed. Segments were taken of the colon, ileum and jejunum. In addition to mucin mRNA expression, morphological changes were observed in the jejunum and ileum. We examined the mRNA expression and biochemical activity of brush border enzyme, sucrase iso-maltase and aminopeptidase, in all three segments. The villous surface area of colitis-induced rats was smaller in jejunum and ileum compared to control. In the jejunum of TNBS-induced rats, goblet-cell volume increased and their density decreased. The relative amount of MUC2 mRNA decreased in the jejunum, ileum and colon of colitis rat. However, MUC3 mRNA expression increased in the ileum and colon of these rats. Sucrase isomaltase expression and activity decreased in the ileum of TNBS-induced rats, while aminopeptidase activity was lower in the jejunum. These observations suggest that intrarectal administration of TNBS to rats influences not only their colon and terminal ileum, but also the proximal ileum and jejunum. Involvement of the ileum and jejunum in TNBS-induced colitis may be related to the systemic reaction of the immune system and mucosa to colitis.

Aminopeptidases↗

The S1P receptor modulator FTY720 prevents the development of experimental colitis in mice.

To evaluate the therapeutic effects of the new synthetic sphingosine-1-phosphate (S1P) receptor modulator, FTY720, we investigated how FTY720 affects the development of dextran sulfate sodium (DSS)-induced colitis and CD4+CD62L+ T cell transfer colitis. BALB/c mice were fed a chow containing 3.5% (wt/wt) DSS to induce colitis. The CD4+CD62L+ T cell transfer colitis was induced by an intraperitoneal injection of CD4+CD62L+ spleen T cells into recipient CB17 SCID mice. The FTY720 was administered by lavage at a dose of 0.3 mg/kg/day. FTY720 was effective in preventing the body weight loss in the DSS-colitis model and the CD4+CD62L+ T cell transfer model. The disease activity index, histological colitis score, and MPO activity were all significantly lower in FTY720-treated mice than in the non-treated mice. Microscopically, mucosal edema, cellular infiltration and epithelial disruption were much more moderate in the FTY720-treated mice than in the non-treated mice. In both colitis models, FTY720 prevented the infiltration of CD4+ T cells into the inflamed colonic lamina propria. In conclusion, the development of DSS-colitis and CD4+CD62L+ T cell transfer colitis were significantly attenuated by FTY720. Since FTY720 is an immunosuppressive product that does not modulate T cell functions, it could be useful in the treatment of IBD patients.

Animals↗

Usefulness of rectal dialysis to determine intrarectal eicosanoids release in ulcerative colitis.

The quantification of the local production of eicosanoids is of interest because it has been implicated in the mucosal damage of ulcerative colitis. In situ production of eicosanoids is not reflected by its urinary or seric levels, requiring invasive examinations. Thus, new non-invasive techniques such as rectal dialysis have been investigated. The purpose of this study was to assess whether the determination of the intrarectal eicosanoid levels measured by rectal dialysis is useful in detecting the presence of rectal inflammation in patients with ulcerative colitis. Thirty one patients with clinically active colitis and 7 controls with irritable bowel syndrome have been studied. A 10 cm long dialysis bag was placed in the rectum for 1 hour. To determine the variability of the technique, the dialysis was repeated the next day in 6 controls. To detect intrarectal eicosanoids release in inactive colitis, rectal dialysis was performed in another group of 15 patients with clinical and endoscopically inactive colitis and compared with 9 patients with active colitis. PGE2, TXB2, and LTB4 were measured in rectal dialysates by immunospecific RIA. Dialysis was well tolerated by all participants. Intrarectal level of every eicosanoid was much higher in active colitis than in controls (p < 0.05) and in inactive colitis (p < 0.001). The mean coefficient of variation of duplicated dialysis ranged from 15 to 28%. In conclusion, rectal dialysis is a non-invasive technique that allows to prove the presence of active inflammation in ulcerative colitis patients.

Adolescent↗

Non infective colitis in infancy: evidence in favour of minor immunodeficiency in its pathogenesis.

Forty two infants below the age of two years presenting with chronic non infective diarrhoea and shown to have histologically proven colitis were investigated over a five year period at this hospital. Allergic colitis was the most common cause of colitis accounting for sixty two percent of the cases. Other colitides diagnosed included: non specific colitis, autoimmune enterocolitis and ulcerative colitis accounting for 9.5% each, severe combined immunodeficiency 7.1% and Crohn's disease 2.8%. A positive family history and a personal history of atopy was obtained in 47.6% and 28.6% of the cases. Serum immunoglobulin A, IgG2 and IgG4 were very low in over 50% of the infants with colitis. Sixty six percent of those with severe combined immunodeficiency, autoimmune enterocolitis and ulcerative colitis (n = 11) had low CD3 and CD4 T lymphocytes with an accompanying elevated CD8 in 2/3 of those with severe combined immunodeficiency. T lymphocytes were normal in those with allergic colitis. We conclude that infants with proven non infective colitis show as a group a high prevalence of IgA, IgG2 and IgG4 deficiency. It is likely that this minor deficiency of mucosal associated immunoglobulin production have a role in the pathogenesis of the colitic process.

Autoimmune Diseases↗

Conservative management of small adenomata in ulcerative colitis.

OBJECTIVE AND METHODS: Patients with chronic ulcerative colitis may develop colitis-related dysplasia and/or sporadic adenomata. Differentiating between these two processes is important because they may dictate different therapeutic approaches. Although distinguishing features of sporadic adenomata versus colitis-related dysplasia have been suggested previously on an a priori basis, they have never been verified by follow-up analysis. We have identified six chronic ulcerative colitis patients whose discrete adenomata were managed conservatively, with subsequent continuation in their surveillance programs. RESULTS: Mean patient age was 69 yr with a mean 21.3 yr of ulcerative colitis. Surveillance endoscopy of 63 patient-yr duration yielded 24 adenomata. A mean follow-up after the initial adenoma diagnosis was 7.2 yr with no carcinoma identified (including the examination of one prophylactic colectomy specimen). One patient, with a 34-yr history of ulcerative colitis and a single sporadic adenoma subsequently developed dysplasia of flat mucosa 14 months later. CONCLUSIONS: Our findings concur with previous reports and indicate that small, discrete adenomata with morphology identical to those seen in the general population occur in patients with ulcerative colitis. Such lesions in patients older than 45 yr, with tubular or tubulovillous architecture and low-grade dysplasia, are effectively treated by polypectomy only and are not necessarily an indication for colectomy. However, sporadic adenomata and colitis-related dysplasia can develop metachronously. It is suggested that subsequent to a diagnosis of sporadic adenoma in a patient with chronic ulcerative colitis, surveillance should increase to colonoscopic examination every 6 to 12 months.

Adenoma↗

Autoimmune hemolytic anemia and positive Coombs test associated with ulcerative colitis.

OBJECTIVES: To estimate the frequency of autoimmune hemolytic anemia and Coombs positivity without overt hemolysis in ulcerative colitis, to determine possible subsets of patients with ulcerative colitis susceptible to this complication, and to assess the efficacy of the applied therapeutic modalities. METHODS: Three hundred and two patients with ulcerative colitis treated at the University Hospital of Heraklion, Crete, over a 6-yr period were included. Within this group, a subgroup of 152 patients were studied prospectively for the presence of a positive direct Coombs test. RESULTS: Autoimmune hemolytic anemia was diagnosed in five of 302 patients with ulcerative colitis (1.7%). One more patient developed Coombs-positive hemolytic anemia, attributed to sulfasalazine. A positive Coombs test without evidence of hemolysis was found in three of 152 patients (2%). The mean age of all Coombs-positive patients was 50.5 yr, and there was a definitive male preponderance (male: female, 2:1). Autoimmune hemolytic anemia occurred during active colitis in all cases. The mean time between the onset of colitis and the diagnosis of autoimmune hemolytic anemia was 17 months. Three of five patients with autoimmune hemolytic anemia (60%) and seven of nine of all Coombs-positive patients (77.7%) had total colitis. All patients with autoimmune hemolytic anemia were treated initially with large doses of corticosteroids. Three of five (60%) had good hematological responses. One patient responded to the addition of azathioprine, and one underwent splenectomy and proctocolectomy. CONCLUSIONS: In this study, the frequency with which autoimmune hemolytic anemia was associated with ulcerative colitis was higher than in previous reports. The complication occurred early in the course of colitis and was related to activity and extent of the disease. In contrast to others studies, we found a preponderance of males. Although corticosteroids and/or immunosuppressive therapy was successful in most of our cases, one patient required surgery.

Adolescent↗

[Ulcerative colitis. Complications and sequelae in relation to the extent of the disease. A 10-year material].

Patients with ulcerative colitis in our catchment area were followed over a ten-years period with the focus on the relation between the extent of inflammation and complications. Total colitis was found in 180 out of 334 patients with known extension, while in 154 of the patients the inflammation was classified as left-sided colitis. The frequency of severe colitis, colectomy and cancer was more or less the same as stated in earlier reports. We observed a difference, however, between the patients with extensive colitis and those with left-sided colitis as regards the course of the disease and the complications related to ulcerative colitis. The risk of liver disease, severe colitis and colectomy were significantly higher among the patients suffering from extensive colitis. Extraintestinal manifestations, on the other hand, were equally distributed among both groups of patients. The reasons for the observed differences are unknown.

Adult↗

Familial and psychological risk factors of ulcerative colitis.

BACKGROUND: The aetiology of ulcerative colitis is still unknown. Several theories have been proposed taking into account psychological influences. AIMS: The present study was undertaken to test the hypothesis of a relationship between certain individual psychological patterns, stress, some familial variables, and ulcerative colitis. PATIENTS: A series of 122 patients with ulcerative colitis and a matched hospital control population were independently studied by a team of physicians and a team of psychologists. METHODS: State-Trait Anxiety Inventory (Form Y) and Sacks' sentence completion tests were submitted to all subjects in both populations. RESULTS: Data showed significantly higher anxiety trait and state in ulcerative colitis patients, whilst 84% of ulcerative colitis patients showed a variety of obsessional traits and an affectivity state characterized by introversion and emotional immaturity. A link was found with regard to relationship with mother, to the condition of single children in the male ulcerative colitis population (41% vs 18% controls), and to last born daughters in the female ulcerative colitis group (47.5% vs 27.9% controls). In addition, a previous stressful life event within the 12-month period prior to the investigation was found in 44.3% of ulcerative colitis patients and in 10.7% of controls. CONCLUSIONS: Psychological disturbances and familial condition are proposed as risk factors, if not actual aetiological variables of ulcerative colitis.

Adult↗

Appendectomy is an independent protective factor for ulcerative colitis: results of a multicentre case control study. The Italian Group for the Study of the Colon and Rectum (GISC)

BACKGROUND: Different exogenous factors are believed to play a role in the pathogenesis of ulcerative colitis. Smoking habits and other risk factors have received much attention. It has recently been reported that appendectomy decreases the risk of ulcerative colitis. AIM: Aim of the study was to further examine the role of appendectomy in ulcerative colitis. METHODS: A large multicentre case control study was performed. Cases were all patients with a recent new diagnosis of ulcerative colitis (from 1990 to 1994) at participating centres. One or two controls attending the orthopaedic and surgical units were considered and matched to cases for age (+/- 5 years), sex and year of diagnosis. A total of 536 cases and 755 controls were enrolled. Mean age of cases was 37.9 years (range 2-92). Assessment of exposure was done by examining the clinical records and by interview, if necessary. Smoking habits, alcohol consumption, use of oral contraceptives, type of occupation and area of residence were also recorded. Odds ratio and 95% confidence intervals were calculated by conditional logistic regression analysis. RESULTS: Forty-one out of the 536 cases (7.6%) and 150 out of the 755 controls (19.9%) had been submitted to appendectomy. A total of 110 out of 536 cases (20.5%) and 135 out of 753 (17.9%) controls had had tonsillectomy. Seven out of 41 cases and 15 out of 755 controls underwent appendectomy for recurrent pain. In all ulcerative colitis patients, appendectomy had been performed before the onset of disease. When data were adjusted for the confounding variables, ulcerative colitis patients were less likely to have had appendectomy compared with controls (odds ratio = 0.3, confidence interval = 0.19-0.48). There was no significant association of ulcerative colitis with tonsillectomy (odds ratio = 1.09, confidence interval = 0.76-1.58). The well recognized inverse association of ulcerative colitis with cigarette smoking was also shown in this study. CONCLUSIONS: The present data emerging from a large multicentre study, confirm that appendectomy has a protective role for the development of ulcerative colitis.

Adolescent↗

Atypical forms of microscopic colitis: morphological features and review of the literature.

Microscopic colitis is defined as a syndrome of chronic watery diarrhea with a chronic inflammatory cell infiltrate in the colonic mucosa but without significant abnormalities at colonoscopy. It encompasses at least two histopathologic entities (ie, collagenous and lymphocytic colitis). The recognition and characterization of microscopic colitis has markedly changed the approach to the evaluation and management of chronic diarrhea. The histologic features of collagenous and lymphocytic colitis are well known to most pathologists. By considering the clinical history and symptoms, the pathologist should be able to reach the correct diagnosis in most cases. However, the spectrum of morphologic changes associated with watery diarrhea syndrome appears to be broader than originally thought. Morphologic changes more often associated with chronic inflammatory bowel disease or even chronic ischemic or infectious colitis have been noted in patients with clinically established microscopic colitis. The data presented in this article suggest that microscopic colitis is a heterogeneous entity, which includes both classic and "atypical" forms. Problems arise when cases do not fit the usual pattern or lack some of the findings that are expected. Pathologists should be aware of the presence of atypical forms of microscopic colitis.

Algorithms↗

Colitis: use of CT findings in differential diagnosis.

PURPOSE: To determine whether colitides can be differentiated based on computed tomographic (CT) features. MATERIALS AND METHODS: The CT scans of 117 patients with documented colitis and colon wall thickening were reviewed. Features evaluated included mural thickness and homogeneity, distribution of bowel involvement, and associated mesenteric and small bowel disease. RESULTS: The mean colon wall thickness in Crohn colitis (11.0 mm +/- 5.1) was significantly greater than in ulcerative colitis (7.8 mm +/- 1.9) (P < .002). Submucosal fat deposition, not observed in the acute colitides, was present significantly more often in ulcerative (61%) than in Crohn colitis (8%) (P = .0001). Exclusive involvement of the right colon and small bowel was most frequent with Crohn and infectious colitis. Abscess was associated almost exclusively with Crohn colitis (35%) but was seen in one patient with radiation colitis. CONCLUSION: Although many CT findings in patients with colitis are nonspecific, some features are helpful in suggesting a specific diagnosis.

Adolescent↗

Indeterminate colitis predisposes to perineal complications after ileal pouch-anal anastomosis.

This study retrospectively evaluated 288 patients who had undergone ileal pouch-anal anastomosis to determine the incidence of perineal complications and to relate these findings to the pathologic diagnosis, with the goal of specifically clarifying the appropriate surgical management of patients with indeterminate colitis. Of these 288 patients, 235 patients (82 percent) had a diagnosis of chronic ulcerative colitis, 18 patients (6 percent) had indeterminate colitis, 6 patients (2 percent) had Crohn's disease, and 29 patients (10 percent) had familial polyposis. All complications occurred at least 6 months after closure of the stoma and required operative therapy. Of 18 patients with indeterminate colitis, 9 patients experienced complications (50 percent) vs. 8 of 235 patients with chronic ulcerative colitis (3 percent), a highly significant difference (P less 0.001). Furthermore, the risk of eventual ileostomy because of perineal complications was 0.4 percent in patients with chronic ulcerative colitis vs. 28 percent in patients with indeterminate colitis (P less than 0.001). We conclude that a diagnosis of indeterminate colitis predisposes the patient undergoing ileal pouch-anal anastomosis to perineal complications, with a resultant high chance of reservoir loss. Ileal pouch-anal anastomosis should be considered with caution in the patient with a diagnosis of indeterminate colitis.

Abscess↗

Clostridium difficile colitis: an increasing hospital-acquired illness.

BACKGROUND: Colitis caused by Clostridium difficile is receiving increased attention as a nosocomial hospital-acquired infection. METHODS: To determine the incidence of C difficile colitis in our facility and the relative proportion of patients dying from the colitis or requiring colectomy for it, we retrospectively reviewed 201 cases of colitis caused by C difficile from 1984 to 1994. RESULTS: The incidence of C difficile colitis appears to be sharply increasing and is associated with the use of cephalosporins. Among patients who subsequently developed C difficile colitis, the most frequent indication for antibiotic use was perioperative prophylaxis; surgical patients comprised 55% of the total cases. Surgical intervention was required for 5% of patients with C difficile colitis, with an operative mortality of 30%. The overall mortality was 3.5% and was associated with a delay in diagnosis. The only discriminative factor between patients who died and those who survived was length of time from symptoms to treatment--5.43 days for survivors versus 10.7 days for those who died (P < 0.05). CONCLUSIONS: Most cases of C difficile colitis seen by surgeons have followed the use of perioperative prophylactic antibiotics. Strict guidelines for using perioperative antibiotics should be observed. Prompt recognition of C difficile colitis and aggressive therapy for it are essential for a favorable outcome.

Adolescent↗

Risk factors associated with fulminant amebic colitis.

Amebic colitis is associated with serious complications and a high fatality rate if it progresses to its fulminant form. The purpose of this retrospective study was to determine the risk factors associated with fulminant amebic colitis. From February 1978 to February 1993, 60 adults were diagnosed with intestinal amebiasis at Chang Gung Memorial Hospital. Sixteen patients with massive bloody diarrhea, persistent systemic toxicity or signs of peritonitis were classified as having fulminant colitis, five of whom progressed to fulminant colitis after admission to the hospital. Forty-four patients with good responses to amebicides and without complications were classified as having moderate colitis. There was no amebiasis-related mortality among patients with moderate colitis. In contrast, five patients with fulminant colitis died. Early diagnosis and surgical treatment significantly decreased mortality when compared with conservative treatment. Significant factors associated with the development of fulminant intestinal amebiasis in univariate analyses were being male, age over 60 years, having an associated liver abscess, progressive abdominal pain, signs of peritonitis, leukocytosis, hyponatremia, hypokalemia and hypoalbuminemia. Only the factors of being over 60 years of age and hypokalemia were important in multivariate analyses. We conclude that early and extensive surgical treatment is mandatory for patients with typical presentations of fulminant amebic colitis on admission to the hospital, such as progression to peritonitis, persistent systemic toxemia and explosive bloody diarrhea. For other patients, especially the elderly and those with low serum potassium levels, close monitoring and observation for signs of fulminant colitis is important.

Adult↗

The classification of feline colitis.

Clinical and pathological features of a variety of forms of feline colitis or enterocolitis were examined and classified into 9 separate entities: Salmonella enterocolitis, the colitis of feline infectious peritonitis, mycotic enterocolitis, acute angiopathic colitis, acute angiopathic colitis with ischaemic ulcers, feline granulomatous colitis, the colitis of feline panleucopenia, feline histiocytic colitis, and feline ulcerative, lymphocytic mucosal-submucosal colitis.

Animals↗