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PubMed2002

Related IgA1 and IgG producing cells in blood and diseased mucosa in ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease in which the colonic mucosa is infiltrated with plasma cells producing IgG autoantibodies. It is not known whether this represents a local mucosal response which has switched to IgG or a peripheral response which may have been initiated by peripheral antigen which homed to the colonic mucosa. The clonal distribution of IgG secreting cells and isotype switched variants in UC is not known. AIMS: To investigate the clonal distribution of mucosal IgG in UC and to search for related IgG and IgA secreting cells in normal and diseased mucosa and blood in UC. To investigate characteristics which may discriminate between the mucosal and peripheral repertoire in the normal mucosa and in UC. PATIENTS: Blood and normal and diseased mucosa from two patients with UC were studied. METHODS: Immunoglobulin gene analysis and clone specific polymerase chain reaction were used to study the clonal distribution and characteristics of IgG and related IgA in the mucosa and blood of patients with UC. RESULTS: The IgG response in the mucosa of UC patients included widespread clones of cells that were present in both the diseased mucosa and blood but that were scarce in normal mucosa. Clonally related IgA class switch variants, all IgA1, were detected but also only in the diseased mucosa and blood. This suggests that these clones home preferentially to the diseased mucosa. We showed that J(H)1 usage was characteristic of the peripheral repertoire, and that examples of J(H)1 usage were observed in mucosal IgG in UC. CONCLUSIONS: Overall, these data are consistent with a model of UC in which a peripheral response is expressed and expanded in the colonic mucosa.

Antibody-Producing Cells↗
PubMed2004

Paradoxical decrease of mitochondrial DNA deletions in epithelial cells of active ulcerative colitis patients.

Ulcerative colitis (UC) is a condition characterized by chronic inflammation targeted at the epithelial layer. In addition to being involved in immune phenomena, UC epithelial cells exhibit decreased oxidation of butyrate, downregulation of oxidative pathway regulatory genes, and overexpression of mitochondrial (mt) genes. We investigated whether these events, which translate an altered energy metabolism, are associated with an abnormal pattern of mtDNA deletions. Highly purified colonocytes were isolated from surgically resected control, involved and uninvolved inflammatory bowel disease mucosa. The frequency, type, and number of mtDNA deletions were assessed by PCR amplification, Southern blot analysis, and cloning and sequencing of amplified DNA fragments. The 4977 mtDNA deletion was less frequent in UC than control and Crohn's disease (CD) epithelium, regardless of patient age. Several other deletions were detected, but all were less common in UC than control and CD cells. The frequency, variety, and number of mtDNA deletions were invariably lower in colonocytes isolated from inflamed mucosa than in autologous cells from noninflamed mucosa. In conclusion, in the absence of inflammation, UC colonocytes exhibit an mtDNA deletion pattern similar to that of control cells, indicating a normal response to physiological levels of oxidative stress. In active inflammation, when oxidative stress increases, the frequency, variety, and number of mtDNA deletions decrease. Because comparable abnormalities are absent in active CD, the mtDNA deletion pattern of active UC suggests that colonocytes respond uniquely to inflammation-associated stress in this condition.

Adult↗
PubMed2005

Complement activation capacity in plasma before and during high-dose prednisolone treatment and tapering in exacerbations of Crohn's disease and ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) are characterized by intestinal inflammation mainly caused by a disturbance in the balance between cytokines and increased complement (C) activation. Our aim was to evaluate possible associations between C activation capacity and prednisolone treatment. METHODS: Plasma from patients with exacerbations of UC (n = 18) or CD (n = 18) were collected before and during high dose prednisolone treatment (1 mg/kg body weight) and tapering. Friedman's two way analysis of variance, Mann-Whitney U test and Wilcoxon signed-rank sum test were used RESULTS: Before treatment, plasma from CD patients showed significant elevations in all C-mediated analyses compared to the values obtained from 38 healthy controls (p < 0.02), and in mannan binding lectin (MBL)-concentration and MBL-C4-activation capacity (AC) values compared to UC patients (p < 0.02). Before treatment, plasma from UC patients showed significant elevations only in the classical pathway-mediated C3-AC compared to values obtained from healthy controls (p < 0.01). After treatment was initiated, significant reductions, which persisted during follow-up, were observed in the classical pathway-mediated C3-AC and MBL-C4-AC in plasma from CD patients (p < 0.05). CONCLUSION: Our findings indicate that C activation capacity is up-regulated significantly in plasma from CD patients. The decreases observed after prednisolone treatment reflect a general down-regulation in immune activation.

Adult↗
PubMed2006

Safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis therapy for ulcerative colitis.

Active ulcerative colitis (UC) is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Therefore, removal of activated circulating leukocytes by apheresis has the potential for improving UC. In Japan, since April 2000, leukocytapheresis using Adacolumn has been approved as the treatment for active UC by the Ministry of Health and Welfare. The Adacolumn is an extracorporeal leukocyte apheresis device filled with cellulose acetate beads, and selectively adsorbs granulocytes and monocytes/macrophages. To assess the safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis (GMCAP) for UC, we reviewed 10 open trials of the use of GMCAP to treat UC. One apheresis session (session time, 60 min) per week for five consecutive weeks (a total of five apheresis sessions) has been a standard protocol. Several studies used modified protocols with two sessions per week, with 90-min session, or with a total of 10 apheresis sessions. Typical adverse reactions were dizziness, nausea, headache, flushing, and fever. No serious adverse effects were reported during and after GMCAP therapy, and almost all the patients could complete the treatment course. GMCAP is safe and well-tolerated. In the majority of patients, GMCAP therapy achieved clinical remission or improvement. GMCAP is a useful alternative therapy for patients with steroid-refractory or -dependent UC. GMCAP should have the potential to allow tapering the dose of steroids, and is useful for shortening the time to remission and avoiding re-administration of steroids at the time of relapse. Furthermore, GMCAP may have efficacy as the first-line therapy for steroid-naive patients or patients who have the first attack of UC. However, most of the previous studies were uncontrolled trials. To assess a definite efficacy of GMCAP, randomized, double-blind, sham-controlled trials are necessary. A serious problem with GMCAP is cost; a single session costs 145 000 ($1 300). However, if this treatment prevents hospital admission, re-administration of steroids and surgery, and improves a quality of life of the patients, GMCAP may prove to be cost-effective.

Adsorption↗
PubMedDate not supplied

[Application of chromoendoscopy to evaluate the severity and interobserver variation in chronic non-specific ulcerative colitis].

BACKGROUND: Ulcerative colitis (UC) is a disease of unknown etiology characterized by chronic and superficial inflammation of colorectum. Chromoendoscopy has been informed as a method to improve evaluation of extension of UC. No reports on this issue have been published in Mexico to date. OBJECTIVE: To investigate usefulness of chromoendoscopy in determination of extension and severity of UC, as well as inter-observer variability. PATIENTS AND METHODS: Twenty five patients with diagnosis of UC were selected from March 2001 to January 2002 to enter this prospective study. Baron scale was used to evaluate UC endoscopic severity and was followed by randomization of patients to receive methylene blue 0.2% (14 cases) or indigo carmine 0.1% (11 cases) for chromoendoscopic assessment. Each case was presented for evaluation to five endoscopists with > 5 years experience in colonoscopy. Histopathologic report was considered gold standard. STATISTICAL ANALYSIS: Weighed Kappa coefficient for endoscopic-pathologic agreement among evaluators was used. RESULTS AND DISCUSSION: There was fair agreement among endoscopic and pathologic diagnoses of each observer with the two tinctures, particularly when using indigo carmine. Chromoendoscopy increased detection of areas affected by UC with minimal or silent activity. CONCLUSIONS: Chromoendoscopy with indigo carmine or methylene blue may increase endoscopic-pathologic agreement for assessment of severity of UC, thus being a helpful complementary technique in these patients.

Adolescent↗
PubMedDate not supplied

[Sensitivity, specificity, and predictive values of the level of hemoglobin, hematocrit and platelet count as an activity index in ulcerative colitis].

INTRODUCTION: Ulcerative colitis (UC) is a disease characterized by relapsing and remitting non-infectious inflammation of the colorectal mucosa. Its heterogeneity makes assessment of the disease's activity a prerequisite for a rational choice of therapy. We aimed to determine sensitivity, specificity, positive and negative predictive values of hemoglobin, hematocrit, and platelets to develop a simplified activity index of UC. MATERIAL AND METHODS: Sixty patients with UC were included and submitted to measurements of hemoglobin, hematocrit, and platelets, as well as sigmoidoscopy and biopsy. Sensitivity and specificity, positive and negative predictive values were correlated with the reported degree of activity in the biopsy. Kruskal-Wallis test was used to determine differences between groups, and Pearson and Spearman rank tests were used to correlate each parameter with the degree of activity. A p value < 0.05 was considered statistically significant. RESULTS: The patients had moderate (n = 15), severe (n = 15), and normal histology as a control group (n = 15). Thirty-four (57%) were female and 26 (43%) were male. Average age was 26 +/- 12.8 years. Sensitivity and specificity for hemoglobin level was 51% and 100% for hematocrit, respectively, 51% and 100% for hematocrit, and 84% and 100% for platelet counts. Spearman's correlation for hemoglobin was r = -0.866 (p < 0.001), for hematocrit r = -0.864 (p < 0.001) and for platelets r = 0.928 (p < 0.001). CONCLUSIONS: Hemoglobin and hematocrit are useful to catalog the degree of activity of UC when it is severe. Platelet count may be a marker of severity at any time, due to its high sensitivity and specificity as a diagnostic test.

Adult↗
PubMed1993

[Taktivin treatment of immunologic disorders in patients with nonspecific ulcerative colitis].

Nonspecific ulcerative colitis (NSUC) varying in severity was treated by conventional methods (49 patients) against combined treatment including tactivin (93 patients). All the patients were examined immunologically at admission and in the course of the treatment. The drug produced a positive effect on immunological status, treatment effectiveness rose, NSUC exacerbations rapidly attenuated.

Adjuvants, Immunologic↗
PubMed1996

The pattern of cell proliferation in neoplastic and nonneoplastic lesions of ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon characterized by repeated episodes of inflammation and epithelial regeneration. Patients with long-standing UC have an increased risk for the development of dysplasia and subsequent colon carcinoma. Because dysplasia likely results from deregulatec cell proliferation, the authors examined Ki-67 immunoreactivity in tissues from UC patients to examine patterns of proliferation in neoplastic and nonneoplastic lesions. METHODS: One hundred and eighty-seven specimens were obtained from 41 patients with UC and each lesion evaluated according to the International Classification for Dysplasia in Inflammatory Bowel Disease. All sections were stained with a monoclonal antibody directed against the proliferation marker Ki-67, and evaluated by three observers. RESULTS: Statistically significant differences in the pattern of Ki-67 immunoreactivity were observed between nonneoplastic and neoplastic lesions. In regenerative mucosa, Ki-67 immunoreactivity localized to the bases of the crypts, and the proliferative zone appeared expanded. In dysplasia, Ki-67 staining was prominent in cells in the superficial mucosa, as well as in cells at the crypt bases. In some dysplasias and all invasive carcinomas, Ki-67 staining was diffusely distributed throughout the crypts, suggesting complete deregulation of normal cell proliferation. CONCLUSIONS: Cell proliferation is markedly increased in patients with UC, and appears abnormally regulated in neoplastic lesions. Furthermore, Ki-67 staining helps delineate areas of dysplasia in cases in which the distinction from regenerative mucosa is unclear. The increased cell proliferation that occurs in patients with UC may predispose the mucosa to mutational events, thereby increasing cancer risk in these patients.

Adult↗
PubMed2002

Granulomatous ulcerative colitis: a re-appraisal of the mucosal granuloma in the distinction of Crohn's disease from ulcerative colitis.

AIMS: To determine whether the presence and location of giant cells or granulomas in relation to crypts distinguishes between ulcerative colitis and Crohn's disease. METHODS AND RESULTS: Twenty-nine large bowel mucosal biopsy specimens showing giant cells and/or granulomas in a background more typical of ulcerative colitis than Crohn's disease were collected between 1986 and 1996. Each was subject to detailed independent analysis by three histopathologists. Follow-up of the cases was by examination of all previous and subsequent gastrointestinal surgical or biopsy material and by scrutiny of the clinical notes by a gastroenterologist. On the basis of the accumulated histological data 10 of these 29 cases were accorded the diagnosis of ulcerative colitis. In nine of these 10 cases the clinical diagnosis, where known, was in keeping with this and all nine contained only crypt-associated giant cells and/or granulomas. The tenth case contained a solitary free-standing granuloma and clinically the patient had perianal disease, suggesting that the true diagnosis was Crohn's disease. CONCLUSIONS: Isolated giant cells and well-defined epithelioid granulomas distant from crypts do not, as a rule, occur in ulcerative colitis, and hence their presence in a colonoscopic biopsy showing features of chronic inflammatory bowel disease is a strong pointer towards the diagnosis of Crohn's disease. Crypt-associated giant cells and granulomas can occur in ulcerative colitis and in themselves are unreliable features for the discrimination between Crohn's disease and ulcerative colitis.

Antigens, CD↗
PubMed1998

Lack of effectiveness of the platelet-activating factor antagonist SR27417A in patients with active ulcerative colitis: a randomized controlled trial. The Platelet Activating Factor Antagonist Study Group in Ulcerative Colitis.

BACKGROUND & AIMS: Platelet-activating factor (PAF) is increased during relapse of ulcerative colitis. In animal models of experimental colitis, specific inhibition of PAF has reduced inflammation. The aim of this study was to evaluate the efficacy and safety of the PAF antagonist SR27417A in moderately active UC. METHODS: A double-blind multicenter trial was conducted during a 28-day period in hospital outpatients with an exacerbation of ulcerative colitis. Patients were randomized to receive 10 mg/day SR27417A or placebo, and both groups were also given 2.4 g mesalazine. Patient classification at the end of the treatment period was based on sigmoidoscopy and clinical scores. RESULTS: One hundred fifty-one subjects entered the study (75 placebo and 76 SR27417A). The remission rate between placebo- and SR27417A-treated patients at 28 days was not significantly different (29.0% and 35.6% respectively; P = 0.44). Similarly, 49.2% treated with SR27417A had a definite or possible improvement of their symptom score compared with 48.3% of those treated with placebo (P = 0.43). Four subjects in the placebo group and 5 subjects in the SR27417A group discontinued the drug treatment because of adverse events. No significant adverse events were thought to be caused by SR27417A. CONCLUSIONS: Although the specific PAF antagonist SR27417A is safe in humans, there is no evidence of efficacy in the treatment of acute ulcerative colitis.

Adult↗
PubMed1992

Relapse-preventing effect and safety of sulfasalazine and olsalazine in patients with ulcerative colitis in remission: a prospective, double-blind, randomized multicenter study. The Ulcerative Colitis Multicenter Study Group.

Forty-nine patients with ulcerative colitis in remission were entered into a prospective, double-blind, multicenter trial comparing the relapse-preventing effect and safety of 4 g sulfasalazine and 2 g olsalazine daily during 48 wk. Of the 46 evaluable patients, 23 were assigned to sulfasalazine and 23 to olsalazine. Seven of 23 patients (30.4%) relapsed on sulfasalazine and six of 23 patients (26.1%) on olsalazine (95% confidence interval of the difference -22.0% to 30.3%). The relapse-free survival curves did not differ significantly at any time during the trial period. In both treatment groups, three patients dropped out because of adverse effects. Four patients on sulfasalazine and six patients on olsalazine experienced minor adverse effects. One patient on sulfasalazine had mild leukopenia, and four patients on sulfasalazine and one patient on olsalazine had decreased levels of haptoglobin. Thus, sulfasalazine and olsalazine are equally effective in maintaining remission of ulcerative colitis and are accompanied by a similar incidence of adverse effects.

Adolescent↗
PubMed2000

Fulminant Ulcerative Colitis.

Fulminant ulcerative colitis necessitates immediate hospitalization. Supportive therapy such as aggressive rehydration, restriction of oral intake, and consideration of parenteral nutrition should be initiated. High-dose intravenous steroids should be started in almost all cases. Antibiotics and cyclosporine should be considered, especially in disease refractory to steroid therapy. Indications for surgery should always be kept in mind, and early involvement of the surgical team is always encouraged. Avoidance of life-threatening complications such as toxic megacolon, hemorrhage, and perforation is the goal of any treatment for fulminant ulcerative colitis.

Journal Article↗
PubMed2002

A prospective, open-label trial assessing dexamethasone pulse therapy in moderate to severe ulcerative colitis.

BACKGROUND: Severe ulcerative colitis is conventionally treated with parenteral corticosteroids followed by oral corticosteroids. Regular use of corticosteroids is associated with side effects. Corticosteroid pulse therapy, i.e., use of supraphysiologic dose followed by complete withdrawal, which is likely to have fewer side effects, was tried in the current study. STUDY: Dexamethasone pulse therapy, i.e., 100-mg/d infusion in 5% dextrose, was used for 3 consecutive days in 14 patients with severe ulcerative colitis. Ulcerative colitis disease activity was assessed on days 7, 15, 30, and 60. The primary end point was defined as the number of patients who achieved clinical remission and an activity index less than 150 at day 15. The second end point was the number of patients who remained in remission and had an activity index less than 150 at 30 and 60 days. None of the patients enrolled got subsequent oral corticosteroids after their 3 days of megadose corticosteroid infusion. RESULTS: Clinical remission was achieved in 93% patients (13 of 14 patients) by day 15. Two of these 13 patients suffered relapse during follow-up, and hence, the clinical remission was sustained in 79% patients at 30 and 60 days. CONCLUSIONS: Dexamethasone pulse therapy is highly effective in inducing remission in patients with ulcerative colitis, but randomized controlled trials are needed to compare dexamethasone pulse therapy with standard oral continuous corticosteroid regimens.

Adult↗
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↗
PubMed2001

Ulcerative colitis of the appendix ('ulcerative appendicitis') mimicking acute appendicitis.

Appendiceal involvement in ulcerative colitis may occur in the setting of either diffuse or distal disease, and is usually diagnosed incidentally at the time of proctocolectomy. The present patient had a rare case of 'ulcerative appendicitis' occurring on a background of clinically quiescent ulcerative colitis, and presented with the signs and symptoms of acute appendicitis.

Acute Disease↗
PubMed2003

Distinct gene expression of osteopontin in patients with ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a multifactorial disorder of unknown etiology. Few studies have applied genome-wide gene expression analysis in colon tissue samples of UC. We report the analysis of mucosal gene expression in UC and noninflamed control specimens. MATERIALS AND METHODS: This study included 7 UC patients who received a total colectomy because of severe total colitis. Normal control colon tissues were obtained at least 10 cm from the area of pathology in 3 colon cancer patients. Ten colonic tissue samples (7 UC and 3 normal control samples) were subjected to high-density oligonucleotide array analysis. To compare differences in the level of gene expression between UC and control samples, Mann-Whitney U-test was used, with significance set at P < 0.05. RESULTS: Twenty-five genes had a 3.0 approximately 23.4-fold higher mRNA expression in UC samples compared with normal samples, whereas three genes had a 3.0 approximately 3.4-fold lower expression in UC samples compared with normal samples. Two genes showing more than a 10-fold increase expression in UC samples were a macrophage metalloelastase (L23808) and a osteopontin (AF052124). It has been said that macrophage metalloelastase is related to ulcer formation of the intestine, whereas osteopontin plays an important role in the pathogenesis of systemic lupus erythematosus and rheumatoid arthritis. CONCLUSION: Our present study supports the previous report that macrophage metalloelastase is related to ulcer formation of UC, and it also indicates the possibility that osteopontin plays an important role in the pathogenesis of UC via increased immune activity.

Adult↗