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Microheterogeneity of acute phase proteins in patients with ulcerative colitis.

AIM: To estimate the serum alpha1-antichymotrypsin (ACT), alpha1-acid glycoprotein (AGP) and transferrin (Tf) concentrations and to evaluate the microheterogeneity of these acute phase proteins in patients with ulcerative colitis. METHODS: Twenty-seven patients with ulcerative colitis (UC) and 17 healthy control subjects were studied. The patients were categorised as severe (n = 9), moderate (n = 10) and mild groups (n = 8) using Truelove and Witts' classification of ulcerative colitis. Microheterogeneity of ACT, AGP and Tf was analysed by crossed immunoaffinity electrophoresis (CIAE) with concanavalin A. In all serum samples standard electrophoresis of serum proteins was performed, iron (Fe) concentration, total iron binding capacity (TIBC) and C-reactive protein (CRP) were also measured. RESULTS: Our patients suffering from ulcerative colitis had significantly higher serum ACT and AGP concentrations and lower serum transferrin concentration in comparison to healthy subjects. Changes in concentrations of acute phase proteins were dependent on the activity of the inflammatory process. The glycosylation patterns of transferrin were related to the inflammation status. We also observed the correlation between ACT and AGP concentrations, patterns of transferrin glycosylation and changes in standard protein electrophoresis or blood cell count. CONCLUSION: The glycosylation patterns of transferrin obtained from patients suffering from ulcerative colitis are highly branched and sialylated compared with those obtained from healthy subjects. In contrast, the glycosylation patterns of transferrin do not differ according to the activity index of ulcerative colitis. The microheterogeneity patterns of AGP and ACT are similar in ulcerative colitis patients and healthy subjects.

Acute-Phase Proteins↗

Considerations of surveillance, dysplasia, and carcinoma of the colon in the management of ulcerative colitis and Crohn's disease.

Patients with ulcerative colitis are at greater risk of developing carcinoma of the colon than the general population even if the exact risk cannot be determined. Thus, an effort must be made to find the carcinoma at its inception or better still before it occurs. Dysplasia serves as a premalignant marker in some cases, and a surveillance program serves to find either dysplasia or the carcinoma. Until more specific premalignant changes are identified, endoscopic surveillance with multiple biopsies offers the best protection for the patient with longstanding ulcerative colitis against carcinoma. There is now sufficient evidence that this also pertains to Crohn's disease of the colon.

Biopsy↗

Circulating autoantibodies against purified colonic mucin in ulcerative colitis.

To clarify the role of colonic mucin in the autoimmune process of ulcerative colitis, circulating antibodies against human colonic mucin were investigated. Purified colonic mucin, obtained from human colonic mucosa by gel filtration, using a Bio-Gel A-1.5-m column and CsCl equilibrium density gradient, was divided into soluble mucin (S-mucin) secreted extracellularly and membranous mucin (M-mucin) binding to cell membrane. Sodium dodecylsulfate polyacrylamide gel electrophoresis and Western blotting analysis showed that antibodies in the serum samples of some patients with ulcerative colitis recognized purified S- and M-mucin of >180-kD. By enzyme-linked immunosorbent assay (ELISA), anti-mucin antibodies were detected in 11 of 60 patients with ulcerative colitis (18%). In contrast, the antibodies were not detected in 22 patients with Crohn's disease. The titers of antimucin antibodies against S-mucin and M-mucin were not different in each patient. By ELISA using mucin in which the sugar chains were destroyed by neuraminidase or NaIO4 treatment, it was demonstrated that anti-mucin antibodies recognized the epitopes of either the sugar chain or the core protein exposed through destruction of the sugar chains. We then investigated the relationship between anti-mucin antibodies and the patients' clinical features. Anti-mucin antibodies were detected in 6 of 15 patients with chronic continuous type ulcerative colitis (40%) and in 5 of 26 patients with relapsing-remitting type (19%), but there was no antimucin antibody-positive serum in patients who had had only one attack without any relapse. These results suggest that anti-mucin antibodies could be a disease marker for ulcerative colitis and that immunological abnormalities in colonic mucin contribute to the persistence of colonic mucosal inflammation.

Autoantibodies↗

Efficacy and tolerability of olsalazine (dipentum) in the treatment of patients with ulcerative colitis--results of a field study.

BACKGROUND/AIMS: In the treatment of ulcerative colitis, 5-aminosalicylic acid is the standard therapy for both acute exacerbations of the disease and the maintenance of remission. Clinical studies have shown that olsalazine (Dipentum)--a prodrug converted to two molecules of 5-ASA by colonic bacteria-induces and maintains remission. This study aimed to investigate the efficacy and tolerability of olsalazine in patients with ulcerative colitis who were being treated in daily practice by private physicians specializing in gastroenterology. METHODOLOGY: A total of 260 patients with ulcerative colitis (aged 17-77 years, 116 men) were studied. The doses of olsalazine and the clinical data (including acute disease symptoms and the occurrence of adverse events) were recorded over a 6-month period. RESULTS: Twenty per cent of patients had pancolitis, 48% had left-sided disease and 32% had proctitis or proctosigmoiditis. At study entry, 86% of patients had active disease; the percentages of these patients in remission after 6 weeks and 6 months were 42% and 91%, respectively. Patients with active disease received a mean dose of olsalazine - 2324mg per day initially and 1325mg per day at 6 months. The corresponding figures for patients in remission at study entry were 1386mg and 1162mg per day, respectively. Seventy-three per cent of patients took olsalazine with food, as recommended. The overall rate of adverse events was low; no serious adverse events occurred. CONCLUSIONS: Olsalazine therapy resulted in a rapid regression in the acute symptoms of ulcerative colitis. Olsalazine was also effective in maintaining remission. The drug was well tolerated.

Adult↗

Coexistence of hyperthyroidism and ulcerative colitis: report of 4 cases and a review of the literature.

Four cases of coexisting hyperthyroidism and ulcerative colitis are presented. In two patients the diseases appeared simultaneously, in one the diagnosis of ulcerative colitis preceded the diagnosis of hyperthyroidism, while in the fourth the diagnosis of hyperthyroidism preceded the diagnosis of ulcerative colitis. Hyperthyroidism intensifies the symptoms of ulcerative colitis and impairs response to therapy. Treatment of both diseases should be conservative. There is no clear explanation for the concurrent existence of the two diseases, although immunological mechanisms seem to play the most significant role. The clinician must bear in mind that coexistence of hyperthyroidism and ulcerative colitis in some patients, although infrequent, nevertheless is a reality, which obviously is very important for the patient's outcome.

Adult↗

[Extra-intestinal complications of ulcerative colitis: arteriovenous thrombosis/embolism].

Thromboembolic episode is a well known extraintestinal complications of ulcerative colitis, but it is a rare complication in clinically. In the literature there are some interesting observations concerning the factors, may play a major role both in the pathogenesis and in the hypercoagulability in ulcerative colitis. However the exact mechanism of hypercoagulability in patients with ulcerative colitis is still unknown. We reviewed the incidence, the activity and severity of the basic disease, the pathogenesis, the treatment, the prognosis of thromboembolic phenomena in patients with ulcerative colitis.

Anticoagulants↗

Protective effect of appendectomy on the development of ulcerative colitis: matched, case-control study.

PURPOSE: Appendectomy and cigarette smoking have been suggested to reduce the chance of developing ulcerative colitis. A case-control study was undertaken to determine the relative incidence of appendectomy in patients with ulcerative colitis. METHODS: This case-control study examined the incidence of appendectomy in patients with ulcerative colitis and patients attending an orthopedic outpatient clinic. RESULTS: Of 100 patients with ulcerative colitis, 75 pairs were matched for age, gender, and cigarette smoking. The ulcerative colitis group had an appendectomy rate of 8 percent (6/75), compared with 21 percent in the control group (P = 0.018). The odds ratio was 3.5 (95 percent confidence interval, 1.15-10.6). CONCLUSIONS: No previous study has examined the effect of appendectomy, controlling for cigarette smoking. This study confirms that appendectomy protects against or reduces the chance of development of ulcerative colitis. A possible immunological explanation for this effect is advanced.

Adolescent↗

Primary adenocarcinoma in an ileostomy: a late complication of surgery for ulcerative colitis.

In the 1950s the treatment of ulcerative colitis was revolutionized by Brooke by way of a colectomy combined with an eversion ileostomy. This procedure is known to be associated with a number of complications that include skin excoriation, stenosis, intestinal obstruction, retraction or prolapse of the stoma, abscess and fistula formation, and ileitis. However, adenocarcinoma arising in the abnormally placed small intestinal mucosa 20 years or more after the initial operation is being increasingly recognized and reported. This article describes one such case and includes an extensive review of the current world literature on the subject of adenocarcinoma arising as a late complication of operation for ulcerative colitis.

Adenocarcinoma↗

Serum bactericidal resistance of faecal Escherichia coli and bactericidal competence of serum from patients with ulcerative colitis.

A microtitre method was developed to screen Escherichia coli from 48 patients with ulcerative colitis and 25 controls for serum resistance. Bactericidal resistance was indicated by a change in colour of indicator due to acid production by viable organisms and quantitated by a change in absorbance. The method clearly differentiated between organisms confirmed as resistant or sensitive by conventional techniques. Twenty four (50%) disease and 14 (56%) control E coli specimens showed serum resistance. Bactericidal competence of sera from patients with ulcerative colitis was assessed by incubating sensitive E coli with sera from 10 patients with ulcerative colitis and pooled normal serum. All sera effectively reduced viable counts to less than 6% of original inoculum. This study shows that serum samples from patients with ulcerative colitis are bactericidally competent and that there is no increase in the number of serum resistant E coli in patients with ulcerative colitis.

Bacteriological Techniques↗

Defensin expression in chronic pouchitis in patients with ulcerative colitis or familial adenomatous polyposis coli.

AIM: Pouchitis develops in ileoanal pouches in up to 50% of patients with ulcerative colitis during the first 10 years after pouch surgery while being rare in patients after proctocolectomy for familial adenomatous polyposis coli (FAP) syndrome. Defensins are major components of the innate immune system and play a significant role in gastrointestinal microbial homeostasis. Pouch defensin and cytokine expression were correlated with states of pouch inflammation to study their role in pouchitis. METHODS: Patients with ulcerative colitis and FAP syndrome were stratified into groups with pouches after surgery, pouches without or with pouchitis. Biopsies from terminal ileum from a healthy intestine or from normal terminal ileum of patients with ulcerative colitis served as controls. mRNA from pouches and controls was analysed for defensin and cytokine expression. RESULTS: Expression of defensins was increased in all pouches immediately after surgery, compared to ileum of controls. Initially, pouches in ulcerative colitis revealed higher defensin expression than FAP pouches. Defensin expression declined in both patient groups and increased again slightly in pouchitis in patients with ulcerative colitis. FAP pouches without pouchitis had strong expression of beta-defensin hBD-1, while all other defensins remained at low levels. Cytokine expression in ulcerative colitis pouches was high, while FAP pouches showed moderately elevated cytokines only after surgery. CONCLUSION: Development of pouchitis correlates with decreased defensin expression in ulcerative colitis in addition to high expression of cytokines. The low incidence of pouchitis in FAP pouches correlates with increased expression of hBD-1 beta-defensin in association with low cytokine levels.

Adenomatous Polyposis Coli↗

[Inflammatory bowel diseases (Crohn disease and ulcerative colitis). Possibilities and limitations of surgical therapy].

Ulcerative colitis can be cured by surgical therapy. Indications for surgery are severe disease not controlled by medical therapy, complication of colitis and prophylaxis of malignancy. Operation of choice is proctocolectomy and ileoanal anastomosis with pelvic ileal pouch, preserving continence. Alternatives are colectomy and ileo-recto-anastomosis if the rectum is free of disease and proctocolectomy with ileostomy if the rectum is involved. Crohn's disease cannot be cured by surgery. Indications for surgery are obstructing or perforating complications of enterocolitis. Basis of surgical therapy is resection, which should be restricted to the severely diseased bowel segment. Structureplasty can correct short bowel stenosis without resection. Surgery for anal Crohn's disease should be limited to drainage of septic complications. Postoperative results support a tendency towards early surgery in ulcerative colitis, while surgery in Crohn's disease should be reserved for severe and complicated disease.

Anastomosis, Surgical↗

Course of severe ulcerative colitis in northern India.

Thirty patients with severe ulcerative colitis were studied prospectively. Sixty percent (18/30) of severe ulcerative colitis were in remission after mean duration of 9.2 days (range 2-20 days) of intensive intravenous therapy without major side effects of steroids. Factors predicting poor response to medical therapy on admission are: stool frequency > or = 9 per day, pulse rate > or = 120/minute, temperature > or = 38 degrees C, Albumin < or = 2 gm, mucosal tags on plain x-ray abdomen and pancolitis.

Adult↗

[Ulcerative colitis in childhood and its differential diagnosis].

Ulcerative colitis occurs before the age of 15 years in 20% and before 20 years in 40% of all patients involved. The frequency of this disease in patients at the University Children's Hospital of Munich has clearly risen over the past years. In many patients we found characteristic differences in history, clinical picture and laboratory results as compared with Crohn's disease. The most important diagnostic procedure is endoscopy of the entire colon. The histological examination of the biopsies taken during colonoscopy differentiated less clearly between these two entities than the macroscopic judgement by the endoscopist. The development of carcinoma must be considered even in children when the disease has lasted for seven years or longer. Ulcerative colitis must be differentiated from infectious diseases of the bowel by direct search for the relevant microorganisms and by serological testing.

Adolescent↗

Staging of the endorectal pull-through operation for ulcerative colitis.

Of 43 patients undergoing operation for ulcerative colitis or polyposis, we found staging of the operation advisable in 7 instances. The initial operation consisted of subtotal colectomy with a Hartman's pouch and an ileostomy. The second procedure was a mucosal proctectomy, ileoanal anastomosis, and construction of a pelvic reservoir into the terminal ileum. The ileostomy was closed as a third procedure with approximately 6 months between each operation. Staging is recommended when emergency operation is required because of bleeding, perforation, or toxic megacolon; when significant technical problems are encountered with the mucosal stripping; or when the surgeon has had limited experience with the procedure. With the addition of staging to the surgeon's armamentarium, it is now possible to offer total colectomy with preservation of rectal continence to virtually all patients suffering from chronic ulcerative colitis.

Adolescent↗

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↗

Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitis.

BACKGROUND: Aminosalicylates are the mainstay of therapy to prevent relapse of quiescent ulcerative colitis. The rationale for using probiotics is based on the evidence implicating intestinal bacteria in the pathogenesis of this disorder. AIM: To evaluate the efficacy of Lactobacillus GG alone or in combination with mesalazine vs. mesalazine as maintenance treatment in ulcerative colitis. PATIENTS AND METHODS: 187 ulcerative colitis patients with quiescent disease were randomized to receive Lactobacillus GG 18 x 10(9) viable bacteria/day (65 patients), mesalazine 2400 mg/day (60 patients) or Lactobacillus GG + mesalazine (62 patients). Disease activity index, endoscopic and histological scores were determined at 0, 6 and 12 months and in case of relapse. The primary end point was to evaluate sustained remission. RESULTS: Overall analysis showed no difference in relapse rate at 6 (P = 0.44) and 12 months (P = 0.77) among the three treatment groups. However, the treatment with Lactobacillus GG seems to be more effective than standard treatment with mesalazine in prolonging the relapse-free time (P < 0.05). CONCLUSIONS: Lactobacillus GG seems to be effective and safe for maintaining remission in patients with ulcerative colitis, and it could represent a good therapeutic option for preventing relapse in this group of patients.

Adult↗

Comparative analysis of histology, DNA content, p53 and Ki-ras mutations in colectomy specimens with long-standing ulcerative colitis.

Neoplastic progression in patients with chronic ulcerative colitis is characterized by the development of epithelial dysplasia, which is accompanied by genetic alterations. This study determined the time of onset of p53 and Ki-ras mutations as well as DNA aneuploidy during histological progression towards carcinoma. In all, 278 samples of 7 colectomy specimens were analyzed by flow cytometry, histology and single-strand conformation polymorphism analysis. Of the samples, 22% (61/278) were dysplastic and 43% (122/278) aneuploid, while 25% (71/278) showed p53 and 4% (11/278) Ki-ras mutations. The correlation between aneuploid status and p53 mutations varied among the patients. A strong correlation was noticed between histological progression from low-grade dysplasia to carcinoma and p53 mutations as well as DNA aneuploidy. Ki-ras mutations were found in 40% (2/5) of the carcinomatous samples. The correlation between p53 mutations and the histological status of the samples suggest the involvement of this genetic event in the development of colon cancer in patients with ulcerative colitis. In contrast to Ki-ras mutations, the appearance of p53 mutations is an early event. Therefore p53 analysis might be helpful in the classification of indefinite dysplasia and in the identification of patients at risk for cancer development. Further studies are necessary to detect the additional genetic alterations preceding the development of DNA aneuploidy.

Aneuploidy↗

Primary biliary cirrhosis and ulcerative colitis: a case report and review of literature.

AIM: To summarize the characteristics of patients suffered from primary biliary cirrhosis associated with ulcerative colitis. METHODS: To report a new case and review the literature. RESULTS: There were 18 cases (including our case) of primary biliary cirrhosis complicated with ulcerative colitis reported in the literature. Compared with classical primary biliary cirrhosis, the patients were more often males and younger similar. The bowel lesions were usually mild with proctitis predominated. While ulcerative colitis was diagnosed before primary biliary cirrhosis in 13 cases, the presentation of primary biliary cirrhosis was earlier than that of ulcerative colitis in our new case reported here. The prevalence of primary biliary cirrhosis among patients of ulcerative colitis was almost 30 times higher than in general population. CONCLUSION: Association of primary biliary cirrhosis with ulcerative colitis is rare. It should be considered in the differential diagnosis of hepatobiliary disease in patients with ulcerative colitis, and vice versa.

Adult↗