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PubMed1977

Immunological studies in ulcerative colitis. VIII. Antibodies to colon antigen in patients with ulcerative colitis, Crohn's disease, and other diseases.

Sera from patients with ulcerative colitis or Crohn's disease had elevated titers to colon antigen from germ-free rats significantly more often than sera from patients with gastroenteritis, irritable colon, non-gastrointestinal diseases, and healthy controls. Elevated anticolon titers in significant frequency were also found in patients with liver cirrhosis, urinary tract infections, and in polyposis coli and their relatives. Females with ulcerative colitis had, on an average, higher titers than men especially in the age group 30 years and over. In Crohn's disease the antibody titers often increased with time--as opposed to those in ulcerative colitis and non-gastrointestinal diseases. In conjunction with results published earlier, the present work supports the assumption that the antibodies in ulcerative colitis patients react with antigenic determinants distinct from those recognized by the colon antibodies present in other groups, including patients with Crohn's disease and polyposis.

Adolescent↗
PubMedDate not supplied

Case of ulcerative colitis associated with oesophageal ulcer.

A case of ulcerative colitis complicated by oesophageal ulcers is reported. A woman was admitted to our hospital because of exacerbations of ulcerative colitis both in 1992 (aged 15 years) and 1995 (aged 18 years). When she was admitted in 1995 she complained of bloody diarrhoea, sore throat and pain on swallowing. Oesophagogastro-duodenoscopy revealed oesophageal ulcers. Oesophageal pH monitoring (24-h) showed no evidence of gastro-oesophageal reflux disease. After the patient was treated she with oral prednisolone showed considerable improvement clinically and endoscopically. Initial dosage was 60 mg/day, and 1 week later, the dosage was gradually dropped since the patient responded favourably. The improvement of the oesophageal lesions coincided with the remission of ulcerative colitis. The oesophageal ulcers are, therefore, thought to be an extracolonic manifestation of ulcerative colitis.

Adolescent↗
PubMed2000

High proliferative activity is associated with dysplasia in ulcerative colitis.

PURPOSE: Ulcerative colitis is associated with an increased risk of colorectal neoplasia. Markers of proliferation are reported to be valuable in the diagnosis of dysplasia in ulcerative colitis. However, it is not known whether dysplastic change or proliferative change occurs first. Whether abnormal proliferation is present in normal-seeming mucosa in ulcerative colitis was investigated. METHODS: Eighteen cancer or high-grade dysplasia specimens and 9 low-grade dysplasia specimens from 5 patients and 51 specimens from 31 patients without neoplasia were studied. Immunostaining with anti-Ki 67 antibody was used to evaluate proliferative activity. Labeling index (in the superficial one-half of crypt) was calculated. Crypts with labeling index more than 0.3 were determined to have abnormal proliferation. RESULTS: The mean +/- standard error of the mean labeling index in specimens negative for dysplasia (0.056+/-0.004) was significantly lower than that in low-grade dysplasia specimens (0.418+/-0.024) and that in high-grade dysplasia specimens (0.503+/-0.027; P < 0.0001). In specimens negative for dysplasia, only 4 (4 cases) of 339 (1.2 percent) crypts had abnormal proliferation, whereas the ratio of crypts with abnormal proliferation was 76 percent (54/71) in low-grade dysplasia and 92.1 percent (35/38) in high-grade dysplasia. The labeling index in background mucosa was 0.139+/-0.009, which was significantly higher than that in specimens negative for dysplasia (P < 0.001). In background mucosa 15.7 percent of crypts showed abnormal proliferation. A follow-up study revealed that two of four cases developed cancer or high-grade dysplasia one and seven years after proliferative abnormality was detected in nondysplastic specimens. CONCLUSION: Ki-67 immunostaining can be an aid in the diagnosis of dysplasia. High proliferating activity in background mucosa suggests that proliferating activity change precedes dysplasia detected with hematoxylin-and-eosin staining.

Biomarkers↗
PubMed1996

A randomised trial comparing mesalazine and prednisolone foam enemas in patients with acute distal ulcerative colitis.

Distal ulcerative colitis can be treated with oral or rectal mesalazine, or both. A foam enema preparation has been developed and its efficacy investigated. The aim of this study was to evaluate the efficacy and safety of mesalazine foam enemas compared with prednisolone foam enemas in the treatment of patients with acute distal ulcerative colitis. Patients aged over 18 years presenting with a relapse of distal ulcerative colitis were randomly allocated treatment with mesalazine foam enema (n = 149 evaluable patients) and prednisolone foam enema (n = 146 evaluable patients) for four weeks. A randomised multicentre investigator blind parallel group trial was conducted. It was found that after four weeks of treatment, clinical remission was achieved by 52% of mesalazine treated patients and 31% of patients treated with prednisolone (p < 0.001). There was a trend in favour of more patients in the mesalazine group achieving sigmoidoscopic remission (40% v 31%, p = 0.10). Histological remission was achieved by 27% and 21% of patients receiving mesalazine and prednisolone respectively. Symptoms improved in both treatment groups. Significantly more mesalazine patients had no blood in their stools after four weeks of treatment (67% v 40%, p < 0.001). Prednisolone treated patients had significantly fewer days with liquid stools than mesalazine patients, with a median of 0 and 1 days respectively by week 4 (p = 0.001). In this study mesalazine foam enema was superior to prednisolone foam enema with regards to clinical remission, this was supported by favourable trends in sigmoidoscopic and histological remission rates. Both treatments were well tolerated.

Acute Disease↗
PubMed1995

Transdermal nicotine as maintenance therapy for ulcerative colitis.

BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers. Having found previously that treatment with transdermal nicotine patches and mesalamine (5-aminosalicylic acid) has a beneficial effect on active colitis, we examined the value of transdermal nicotine for the maintenance of remission. METHODS: We treated 80 patients with ulcerative colitis in remission with either transdermal nicotine or placebo patches for six months in a randomized, double-blind study. Incremental doses of nicotine were given for the first three weeks to achieve a maintenance dose; most patients tolerated 15 mg for 16 hours daily. All patients were taking mesalamine preparations as maintenance treatment at entry into the study; this treatment was stopped once the maintenance dose of nicotine was achieved. Clinical, sigmoidoscopic, and histologic assessments were made at the beginning and the end of the study, or at relapse. Side effects and serum nicotine and cotinine concentrations were monitored throughout the study. RESULTS: There was no significant difference in the number of relapses between the groups. Twenty-two patients in the nicotine group were prematurely withdrawn from the study, 14 because of relapse and 8 for other reasons, including side effects and protocol violations. In the placebo group, 20 patients were withdrawn prematurely, 17 because of relapse and 3 for other reasons. Among patients using 15-mg nicotine patches, serum nicotine and cotinine concentrations were lower than expected and may reflect poor compliance. Side effects were reported by 35 patients--21 in the nicotine group and 14 in the placebo group--the most common of which were nausea, lightheadedness, and itching. CONCLUSIONS: Transdermal nicotine alone was no better than placebo in the maintenance of remission of ulcerative colitis, and premature withdrawal due to side effects was more common in the nicotine group.

Administration, Cutaneous↗
PubMedDate not supplied

Ulcerative colitis activity index: a useful prognostic factor for predicting ulcerative colitis outcome.

We evaluated the usefulness of various parameters in predicting the prognosis of ulcerative colitis. The records of 73 patients with ulcerative colitis were examined retrospectively. Patients were divided into two groups according to whether they had received only 5-aminosalicylic acid (5-ASA; n = 26) or glucocorticoids and/or azathioprine with or without 5-ASA (n = 47). The disease extent, endoscopic activity and ulcerative colitis activity index (UCAI) before therapy were recorded, together with the disease outcome. No statistically significant differences in outcome were observed in relation to therapy group, disease extent or endoscopic activity. UCAI had a significant effect on outcome, however: patients with lower UCAI values were more likely to remain in remission and less likely to require urgent surgery or experience a fatal outcome than those with higher UCAI values. This difference was apparent in both treatment groups. Thus a high pre-treatment UCAI may indicate a worse outcome.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Smoking, humoral immunity, and ulcerative colitis.

Since ulcerative colitis predominantly affects non-smokers and ex-smokers we have examined the possibility that smoking modifies the humoral immune response to an antigenic challenge from the gut lumen. Gut lavage was used in healthy subjects and patients with ulcerative colitis, including both smokers and non-smokers. Antibodies in the intestinal fluid to Escherichia coli (five pooled serotypes), Candida albicans, gliadin, ovalbumin, and beta lactoglobulin were measured by ELISA to determine specific antibody concentrations of IgG, IgA, and IgM classes. Total IgG, IgA, and IgM were also measured in intestinal secretions and serum. In addition, circulating antibody concentrations of IgG, IgA, and IgM to three gut commensals - E coli (five pooled serotypes) C albicans, and Poroteus mirabilis were measured. There was a significant reduction in the IgA concentration in intestinal fluid of smokers with ulcerative colitis compared with healthy non-smoking controls. No other significant differences were found between the groups. Overall, these data are not consistent with the idea that smoking suppresses immune responses in the gut and suggest that the effect of smoking in colitis is mediated by another mechanism.

Adult↗
PubMed1999

Diversion colitis: a trigger for ulcerative colitis in the in-stream colon?

The aetiology of ulcerative colitis is unknown. Two patients without pre-existing inflammatory bowel disease in whom end colostomy for faecal incontinence was complicated by diversion colitis in the defunctioned rectosigmoid colon, are described. In both instances, colitis with the clinical, colonoscopic, and microscopic features of ulcerative colitis developed about a year later in the previously normal in-stream colon proximal to the colostomy. These cases suggest that diversion colitis may be a risk factor for ulcerative colitis in predisposed individuals and that ulcerative colitis can be triggered by anatomically discontinuous inflammation elsewhere in the large intestine.

Adolescent↗
PubMed2000

Oral 5-aminosalicylic acid for maintaining remission in ulcerative colitis.

OBJECTIVES: To assess the efficacy, dose-responsiveness and safety of the newer release formulations of 5-aminosalicylic acid (5-ASA) compared to placebo or sulfasalazine (SASP) in the maintenance of remission in ulcerative colitis. SEARCH STRATEGY: A computer-assisted literature search for relevant studies (1981-1998) was performed using MEDLINE, BIOS, the Cochrane Controlled Trials Register, the Inflammatory Bowel Disease Trials Register, and Science Citation Index, followed by a manual search of reference lists from previously retrieved articles, review articles, symposia proceedings, and abstracts from major gastrointestinal conferences. SELECTION CRITERIA: Studies were accepted for analysis if they were prospective, randomized, double-blinded, and placebo- or SASP-controlled clinical trials of parallel design with treatment duration of at least six months. DATA COLLECTION AND ANALYSIS: Based on an intention to treat principle, the primary outcome was the failure to maintain clinical or endoscopic remission. Secondary outcomes were the number of patients experiencing adverse events, the number of patients withdrawn due to adverse events, and exclusions or withdrawals after entry into the study (not due to relapse). All data were analyzed using the Peto odds ratio and corresponding 95% confidence intervals (CI). MAIN RESULTS: The Peto odds ratio for the failure to maintain clinical or endoscopic remission (withdrawals and relapses) for 5-ASA versus placebo was 0. 47 (95% CI, 0.36 to 0.62) with an NNT of 6. These values were also calculated for the trials in which SASP and 5-ASA were compared, revealing an odds ratio of 1.29 (95% CI, 1.05 to 1.57), with a negative NNT value (-19), suggesting a higher degree of therapeutic effectiveness for SASP. SASP and 5-ASA had similar adverse event profiles, with odds ratios of 1.16(0.62 to 2.16), and 1.31(0.86 to 1.99), respectively. The NNH values were determined to be 171 and 78 respectively. REVIEWER'S CONCLUSIONS: The newer 5-ASA preparations were superior to placebo in maintenance therapy. However, the newer preparations had a statistically significant therapeutic inferiority relative to SASP.

Administration, Oral↗
PubMed2000

Oral 5-aminosalicylic acid for inducing remission in ulcerative colitis.

OBJECTIVES: To assess the efficacy, dose-responsiveness and safety of the newer release formulations of 5-aminosalicylic acid (5-ASA) compared to placebo or sulfasalazine (SASP) for the induction of remission in active ulcerative colitis. SEARCH STRATEGY: A computer-assisted literature search for relevant studies (1981-1998) was performed using MEDLINE, BIOS, the Cochrane Controlled Trials Register and the Science Citation Index, followed by a manual search of reference lists from previously retrieved articles, review articles, symposia proceedings, and abstracts from major gastrointestinal conferences. SELECTION CRITERIA: Studies were accepted for analysis if they were randomized, double-blinded, and controlled clinical trials of parallel design, with treatment durations of a minimum of four weeks. DATA COLLECTION AND ANALYSIS: Based on an intention to treat principle, the outcomes of interest in the treatment of active disease were the failure to induce global/clinical remission, global/clinical improvement, endoscopic remission, or endoscopic improvement. MAIN RESULTS: 5-ASA was superior to placebo with regard to all measured outcome variables. For the failure to induce global/clinical improvement or remission, the pooled Peto odds ratio was 0.51 (95% CI, 0.35 to 0.76). A dose-response trend for 5-ASA was also observed. When 5-ASA was compared to SASP, the pooled Peto odds ratio was 0.87 (CI, 0.63 to 1.21) for the failure to induce global/clinical improvement or remission, and 0.66 (CI, 0.42 to 1.04) for the failure to induce endoscopic improvement. SASP was not as well tolerated as 5-ASA. REVIEWER'S CONCLUSIONS: The newer 5-ASA preparations were superior to placebo and tended towards therapeutic benefit over SASP. However, considering their relative costs, a clinical advantage to using the newer 5-ASA preparations in place of SASP appears unlikely.

Aminosalicylic Acids↗
PubMed1984

Serum angiotensin converting enzyme in Crohn's disease, ulcerative colitis and peptic ulceration.

Serum angiotensin converting enzyme (ACE) activities were determined in patients with different types of inflammatory disease of the gastrointestinal tract, in patients with peptic ulcer, and in healthy volunteer subjects. ACE activity in serum was measured by its in vitro ability to cleave hippuric acid from the synthetic tripeptide hippuryl-L-histidyl-L-leucine. The hippuric acid so formed was quantified by high performance liquid chromatography and results are expressed as nmol hippuric acid produced/ml plasma/min. ACE activity was 27.4 +/- 7.7 (mean +/- SD, n = 37) in control subjects and was not related to age or sex. Compared to controls, patients with ulcerative colitis had similar ACE values (26.5 +/- 7.7, n = 16) while, surprisingly, there was a significant (p less than 0.01) increase in the enzyme in those with active peptic ulcers (33.8 +/- 8.8, n = 21) irrespective of whether the site of ulceration was gastric or duodenal. In a mixed group of patients with active and inactive Crohn's disease, ACE activity (24.8 +/- 7.2, n = 19) was not different from controls. However, ACE activity was significantly (p less than 0.02) depressed in active Crohn's disease (19.8 +/- 7.3, n = 8) compared to either control subjects or patients with inactive disease (28.4 +/- 6.3, n = 9). There was wide inter-patient variability in ACE levels and hence the diagnostic value of random measurements of this enzyme in Crohn's disease is limited.

Adolescent↗
PubMed2026

Genome-wide Association Studies of the Pathogenic Sphingosine-1-Phosphate Gene in Ulcerative Colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease that can lead to malignancies over time. Sphingosine-1-phosphate (S1P) receptor signaling affects lymphocyte trafficking and vascular integrity, influencing intestinal inflammation. This study aimed to identify S1P-related key genes in UC. METHODS: Differentially expressed genes (DEGs) between the UC and control groups were analyzed in the GSE87473 (training) dataset. Genes overlapping between the DEGs and S1P-related genes were considered candidate genes. These genes were incorporated into machine learning algorithms and subjected to expression analysis to identify key genes. Gene functions were determined through a gene&#x2013;gene interaction network, enrichment analysis, and immune cell infiltration analysis. In addition, transcription factor&#x2013;mRNA and mRNA&#x2013;miRNA&#x2013;lncRNA networks were constructed. Finally, reverse transcription&#x2013;quantitative polymerase chain reaction (RT-qPCR) was performed to evaluate the expression of key candidate genes in UC and control tissues. RESULTS: This study identified two key genes (SPHK2 and SPNS2) associated with UC. Notably, SPHK2 expression was lower and SPNS2 expression was higher in the UC group in both training and validation datasets and in clinical UC tissues (RT-qPCR). The area under the curve values of SPHK2 and SPNS2 exceeded 0.7 in both datasets, indicating that the genes had good diagnostic efficacy for UC. Consistently, the nomogram showed that the two genes had promising diagnostic value in UC. SPHK2 and SPNS2 were found to be localized to the plasma membrane. The correlations of the two genes with different immune cells showed significantly opposite trends. In particular, SPHK2 had the strongest positive correlation with M2 macrophages (r = 0.6) and the strongest negative correlation with neutrophils. Moreover, mRNA&#x2013;miRNA&#x2013;lncRNA and transcription factor&#x2013; mRNA networks of the key genes were constructed. CONCLUSION: This study suggests that SPHK2 and SPNS2 are key genes associated with UC, highlighting their potential as effective diagnostic biomarkers.

Humans↗
PubMedDate not supplied

Outcome of patients undergoing ileal pouch-anal anastomosis for left-sided chronic ulcerative colitis.

Chronic ulcerative colitis is not a uniform disease entity because the clinical pattern and disease characteristics differ on the basis of the anatomic location of the inflammation. The aim of this study was to compare the preoperative characteristics, postoperative complications, and long-term functional outcome of ileal pouch-anal anastomosis (IPAA) in patients with left-sided colitis to those same characteristics in patients with pancolitis. Between 1990 and 1996, a total of 565 patients underwent IPAA for chronic ulcerative colitis at our institution. Of these, 111 patients were determined to have left-sided involvement, whereas 283 patients had pancolitis. The mean age at surgery was greater in the patients with left-sided colitis (37 years vs. 34 years, P = 0.01), and the mean duration of disease (8.7 years vs. 7.7 years, P = 0.05) tended toward a significant difference between the left-sided colitis and pancolitis groups. The complication rates were similar with the exception of small bowel obstructions, for which there was a higher incidence in the group with left-sided colitis (27% vs. 13%, P = 0.002) at 5 years. The incidence of pouchitis (43% vs. 39%) at 5 years was comparable. Long-term functional results and quality-of-life assessment did not show any significant differences between the two groups. We were unable to detect any correlation between the extent of colon involvement and the subsequent incidence of pouchitis, long-term pouch function, and quality of life. Patients with left-sided colitis were older, had a relatively longer duration of disease, and were at increased risk for postoperative small bowel obstruction as compared to patients with pancolitis.

Adult↗
PubMed1999

Randomized clinical trial of Plantago ovata seeds (dietary fiber) as compared with mesalamine in maintaining remission in ulcerative colitis. Spanish Group for the Study of Crohn's Disease and Ulcerative Colitis (GETECCU).

OBJECTIVE: Butyrate enemas may be effective in the treatment of active distal ulcerative colitis. Because colonic fermentation of Plantago ovata seeds (dietary fiber) yields butyrate, the aim of this study was to assess the efficacy and safety of Plantago ovata seeds as compared with mesalamine in maintaining remission in ulcerative colitis. METHODS: An open label, parallel-group, multicenter, randomized clinical trial was conducted. A total of 105 patients with ulcerative colitis who were in remission were randomized into groups to receive oral treatment with Plantago ovata seeds (10 g b.i.d.), mesalamine (500 mg t.i.d.), and Plantago ovata seeds plus mesalamine at the same doses. The primary efficacy outcome was maintenance of remission for 12 months. RESULTS: Of the 105 patients, 102 were included in the final analysis. After 12 months, treatment failure rate was 40% (14 of 35 patients) in the Plantago ovata seed group, 35% (13 of 37) in the mesalamine group, and 30% (nine of 30) in the Plantago ovata plus mesalamine group. Probability of continued remission was similar (Mantel-Cox test, p = 0.67; intent-to-treat analysis). Therapy effects remained unchanged after adjusting for potential confounding variables with a Cox's proportional hazards survival analysis. Three patients were withdrawn because of the development of adverse events consisting of constipation and/or flatulence (Plantago ovata seed group = 1 and Plantago ovata seed plus mesalamine group = 2). A significant increase in fecal butyrate levels (p = 0.018) was observed after Plantago ovata seed administration. CONCLUSIONS: Plantago ovata seeds (dietary fiber) might be as effective as mesalamine to maintain remission in ulcerative colitis.

Adult↗
PubMed1996

Transdermal nicotine compared with oral prednisolone therapy for active ulcerative colitis.

BACKGROUND: Ulcerative colitis is largely a disease of non-smokers. Previous controlled trials have shown benefit with transdermal nicotine when given with 5-aminosalicylic acid in active disease but not when given alone as maintenance therapy. OBJECTIVE: To examine nicotine alone compared with prednisolone in active disease. PATIENTS AND METHODS: Sixty-one patients with active ulcerative colitis were treated with either transdermal nicotine patches or 15 mg prednisolone for 6 weeks in a randomized, double-blind study. Incremental doses of nicotine were given for the first 9 days; patients tolerated between 15 and 25 mg daily. Most patients were taking mesalazine at entry which was discontinued at day 10; a few were taking topical steroids which were discontinued at the onset. Clinical, sigmoidoscopic and histological assessments were made at baseline and 6 weeks, or at premature withdrawal. Symptoms were recorded on a diary card, and the clinician made a global clinical assessment. Side effects and serum nicotine and cotinine concentrations were monitored throughout the study. RESULTS: Forty-three patients completed the 6-week trial; of these, 6 of 19 in the nicotine group achieved full sigmoidoscopic remission compared with 14 of 24 with prednisolone (P = 0.08). In those who completed the 6-week study, there was significant improvement within both the nicotine and prednisolone group for the St Mark's score (P < 0.05 and P < 0.01, respectively), Global Clinical Grade (P < 0.01 for both), blood in the stool (P < 0.05 and P < 0.01), abdominal pain (P < 0.05 and P < 0.01) and sigmoidoscopic score (P < 0.01 and P < 0.001); differences between groups tend to favour prednisolone, but none reach statistical significance. However, on intention-to-treat analyses there is little clear evidence of improvement in either group apart from sigmoidoscopic score in which prednisolone was associated with a significantly greater improvement than nicotine (P < or = 0.05). The nicotine group had more withdrawals than the prednisolone group, 11 versus 7, respectively (P = 0.23), both for deterioration (6 vs. 5) and side effects (5 vs. 2, P = 0.15). Side effects were more frequently reported in the nicotine group (average 1.47 episodes per person) than the prednisolone group (average 0.61; P = 0.03), the most common of which were nausea, light-headedness and tremor. CONCLUSION: In those who managed to complete the 6-week study, nicotine alone appeared to be of only very modest benefit in acute colitis and was not as effective as 15 mg of prednisolone daily.

Administration, Cutaneous↗
PubMed1986

Enteroendocrine cell hyperplasia, carcinoid tumours and adenocarcinoma in long-standing ulcerative colitis.

Chronic ulcerative colitis may be accompanied by a variety of epithelial changes, including loss of goblet cells, Paneth cell metaplasia, villous metaplasia, and dysplasia. Total colitis is also accompanied by an increased incidence of adenocarcinoma. All these changes are assumed to be secondary to repeated mucosal damage, but how they develop is unknown. Little attention has been paid to the enteroendocrine cell population, despite the postulated role of these cells as producers of trophic hormones. We describe two patients with long-standing ulcerative colitis who developed both adenocarcinoma and carcinoid tumours. In both, there were increased numbers of enteroendocrine cells in the uninvolved colonic mucosa. We suggest that an increased enteroendocrine cell mass may be part of a non-specific reaction to chronic mucosal injury, and by producing an elevated level of trophic hormones may act as a promoter in the development of neoplasia.

Adenocarcinoma↗
PubMed1977

Total colectomy and mucosal proctectomy with preservation of continence in ulcerative colitis.

Since ulcerative colitis is a mucosal disease, it would appear possible to remove the diseased rectal mucosa and preserve all anorectal musculature. When performed in conjunction with total colectomy, the terminal ileum could then be placed inside the retained muscular wall of the rectum and anastomosed to the anus. This would remove all of the disease and yet preserve anorectal continence. Seventeen patients with chronic ulcerative colitis have undergone this operation with satisfactory results in 15 and no deaths. Many details of preoperative, operative and postoperative management are presented which are imperative for a successful result. Sufficient experience has been gained that the operation can now be recommended.

Abscess↗