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Variation in severity assessment and initial mesalamine dose selection for ulcerative colitis in community practice.

BACKGROUND AND AIMS: Ulcerative colitis treatment is based largely on anatomic extent of inflammation and severity. Clinical severity is designated by the terms mild, moderate, or severe. The aims of this study are to assess consistency between: (1) community physicians and established treatment guidelines in their respective operational definitions of severity and (2) clinical severity ratings and resulting treatment. METHODS: Medical records of 411 patients who were successfully treated with mesalamine delayed release tablets without requiring steroids were reviewed. Data recorded included the prescribed dose of mesalamine, clinical symptoms, and physician's global assessment (PGA). RESULTS: Physicians were moderately consistent with the American College of Gastroenterology Guidelines in their assignments of PGA (kappa=0.57, P<0.001). An alternative decision rule, which deviated from the guidelines by placing a higher proportion of patients in the mild category, yielded a significantly higher kappa of 0.69 (P<0.001). The associations between severity measures and mesalamine dose yielded tau statistics of 0.13, 0.16, and 0.14 (all P<0.001), respectively for PGA, number of stools per day and percentage of stools with blood. CONCLUSIONS: Ulcerative colitis treatment quality may be enhanced by promoting a more consistent terminology for disease severity and reducing the unexplained variation in treatment dosing.

Adolescent↗

Is age relevant to functional outcome after restorative proctocolectomy for ulcerative colitis?: prospective assessment of 122 cases.

OBJECTIVE: Restorative proctocolectomy for mucosal ulcerative colitis is well established. However, the effect of age on physiologic sphincter parameters is poorly understood. Our objective was to determine whether age at the time of restorative proctocolectomy correlates with physiologic changes. SUMMARY BACKGROUND DATA: In the approximately 20 years during which restorative proctocolectomy has been performed for ulcerative colitis, the indications have changed. Initially, the procedure was recommended only in patients under approximately 50 years. However, the procedure has been considered in older patients because of the increasing age of our population, the increasing frequency of recognition of patients during the "second peak" of mucosal ulcerative colitis, and the decreasing morbidity rates, due to the learning curve and to newer techniques, such as double-stapling. Few authors have presented data analyzing the effects of this operation in older patients. METHODS: One hundred twenty-two patients who had undergone a two-stage restorative proctocolectomy for mucosal ulcerative colitis were divided into three groups according to age: group I (>60 years), 11 men, 6 women; group II (40-60 years), 29 men, 18 women; and group III (<40 years) 29 men, 29 women. The patients were prospectively evaluated using anal manometry and subjective functional results. Comparisons were made before surgery, after colectomy and before closure of ileostomy, and at 1 or more years after surgery. RESULTS: There were no significant differences among the groups relative to manometric results, frequency of bowel movements, incontinence scores, or overall patient satisfaction. The postoperative mean and maximum resting pressures were significantly reduced (p < 0.001), and conversely the sensory threshold (p < 0.005) and capacity (p < 0.001) were increased in all groups up to 1 year after surgery. There were no statistically significant changes in the squeeze pressure or length of the high-pressure zone in any group at any point in time. After surgery, the mean and maximum resting pressures had returned to 80% of their original values. CONCLUSION: Although anorectal function is transiently somewhat impaired after restorative proctocolectomy, the impairment is not an age-related phenomenon.

Adult↗

Prognostic value of rectal biopsies in idiopathic ulcerative colitis.

Eighty seven biopsies and five total colectomy specimens following surgery were studied in 40 cases with idiopathic ulcerative colitis. They were categorised as acute ulcerative colitis with evidence of chronic activity in the first or subsequent biopsies (10 cases), chronic active ulcerative colitis (25 cases), and chronic quiescent ulcerative colitis (5 cases). The histological criteria were predefined with special reference to chronic crypt changes. Repeat biopsies were available in 28 cases and were found to be valuable in diagnosis and follow up of the disease.

Acute Disease↗

Sclerosing cholangitis in ulcerative colitis.

In a 5-year period 48 (14%) of 336 patients with ulcerative colitis were found to have hepatobiliary disease. The bile ducts were examined in 35 of these patients, and optimal visualization of both intra- and extra-hepatic bile ducts was obtained in 26. Duct changes compatible with sclerosing cholangitis were found in 14 patients. This finding of sclerosing cholangitis in 4% of all patients admitted with ulcerative colitis by far exceeds previous estimations on the incidence of sclerosing cholangitis in ulcerative colitis. The entire colon was usually affected, and the symptoms of the bowel disease were most often mild or moderate. The age at the onset of the colitis was usually below 20 years in patients with combined ulcerative colitis and hepatobiliary disease. In most patients the hepatobiliary disease gave no symptoms. Biochemical data and the histological findings in the liver biopsies did not distinguish between patients with hepatobiliary disease with and without sclerosing cholangitis. Our follow-up study has so far shown that most patients with sclerosing cholangitis remain asymptomatic for a considerable period of time.

Adolescent↗

[The computed tomographic morphology of Crohn's disease and ulcerative colitis].

PURPOSE: To assess the value of computed tomography for the diagnosis of Crohn's disease and ulcerative colitis. METHOD: We analysed the CT examinations of 109 patients with 197 involved bowel locations. 81 patients suffered from Crohn's disease, 28 from ulcerative colitis. Diagnosis was based on the combination of clinical, endoscopic and histopathologic findings. Three radiologists evaluated the CT series concerning the presence of morphologic changes analogous to conventional radiographic findings. RESULTS: In Crohn's disease, we found irregular outer contours in 26% of cases. The bowel wall was thickened in 82%. In acute phases, the bowel wall was thickened in 100%. Abscess and fistula as complications of inflammatory disease were present in 26 and 14% respectively. In ulcerative colitis, a target sign of the bowel wall was present in 40%, whereas in Crohn's disease a homogeneous wall density was present in all but two cases. Reduced attenuation due to submucosal fat deposits was found in 16% and mucosal tunneling in 27% of cases with ulcerative colitis. Even if severe mucosal destructions were found, the outer contour of the gut was smooth and regular in 95% of the ulcerative colitis cases. CONCLUSION: CT can provide additional information on acuity, extent and complications in inflammatory bowel disease. In combination with conventional radiographic findings a three-step classification for Crohn's disease and ulcerative colitis (early changes, acute and chronic phase) can be proposed.

Adolescent↗

Development of ulcerative colitis after heart transplantation during immunosuppressive therapy.

BACKGROUND: Cardiac transplantation has become an accepted treatment modality for end-stage heart failure. Immunosuppressive agents, which are used after transplantation, are considered as therapeutic options for inflammatory bowel disease. CASE REPORT: We report on a 53-year-old patient who was treated for 2 years with cyclosporine A, azathioprine and prednisolone after heart transplantation. He developed a distal colitis with all features of ulcerative colitis. An infectious or ischemic etiology was carefully excluded. In spite of high-dose treatment with prednisolone the patient's abdominal symptoms worsened and he developed a progression of the inflammation in the entire colon and a colectomy with ileostomy was necessary. The histology was consistent with ulcerative colitis. After colectomy he recovered and remained in a good state of health. CONCLUSIONS: This report supports the concept that new onset inflammatory bowel disease can develop in a heart transplantation recipient in spite of immunosuppression.

Biopsy↗

Effects of colectomy on gallbladder motility in patients with ulcerative colitis.

In order to gain insight into the possible mechanisms involved in gallstone formation in colectomized ulcerative colitis patients, we studied gallbladder motility by means of ultrasonography in three groups of subjects: controls (N = 40) and ulcerative colitis patients without (N = 30) and with (N = 20) colectomy. Impaired gallbladder emptying after a liquid fatty meal stimulus was observed in ulcerative colitis patients with colectomy compared with those obtained in ulcerative colitis patients without colectomy and controls (P = 0.001). The maximum percentage of gallbladder emptying also, was significantly lower (59.8%) than those seen in ulcerative colitis patients without colectomy (74.5%) and controls (77.8%) (P = 0.001). Diminished gallbladder emptying with ensuing stasis might be a contributory factor to the increased prevalence of gallstones in colectomized patients.

Adult↗

Patchy cecal inflammation associated with distal ulcerative colitis: a prospective endoscopic study.

OBJECTIVES: It is generally believed that the mucosal inflammation in ulcerative colitis is characterized by a diffuse, continuous involvement starting from the rectum without "skip areas." It was the aim of this study to examine 20 patients with established "left-sided ulcerative colitis" prospectively by ileocolonoscopy with biopsies to determine the extent and the continuity of the mucosal inflammation and the incidence of skip lesions in ulcerative colitis. METHODS: Twenty patients with left-sided ulcerative colitis underwent a complete ileocolonoscopy with biopsies of the terminal ileum and all colonic segments. The patients remained in clinical follow-up for at least 8 yr after the initial examination. RESULTS: The upper margin of inflammation was sharply demarcated in 6 patients and gradual in 14. Segmental inflammation, separated from the distal inflamed segment by apparently uninvolved mucosa, was found in 15 patients (75%) and always included the area around the appendiceal orifice. The correlation between endoscopic abnormalities and histological changes was excellent. CONCLUSION: In so-called "left-sided" ulcerative colitis distal involvement may be accompanied by more proximal areas of inflammation, particularly in the periappendiceal area of the cecum.

Adolescent↗

[Crohn disease and ulcerative colitis from the surgical viewpoint].

Crohn's Disease and Ulcerative Colitis, both chronic-recurrent inflammatory bowel diseases, are totally different with respect to surgical indication and therapy. While in Crohn's Disease it is intended to achieve a longer interval of resting disease at typical complications or failure of drug-therapy, in Ulcerative Colitis definitive cure is possible. Because of the significant lower mortality and complication-rate of elective surgery compared to emergency cases, surgical treatment should be considered very early as therapeutic strategy. The resection area in Crohn's Disease should be confined to a minimum, because even a wide resection is no guaranty for nonrecurrence. In Ulcerative Colitis proctocolectomy provides a reliable protection against colonic carcinoma.

Anal Canal↗

Association between ulcerative colitis and systemic lupus erythematosus: report of two cases.

BACKGROUND: Common aetiopathogenic factors may explain the association of ulcerative colitis with autoimmune disorders such as systemic lupus erythematosus. PATIENTS: We report two cases of ulcerative colitis associated with idiopathic systemic lupus erythematosus: one patient who developed ulcerative colitis 11 years after having been diagnosed as a case of systemic lupus erythematosus and one case of simultaneous appearance of the two diseases. The lupus clinical manifestations were in neither case correlated with the treatment of ulcerative colitis. CONCLUSION: The association between ulcerative colitis and systemic lupus erythematosus is rare. Although a chance occurrence cannot be excluded it is possible that both conditions share some genetic or immunological defects.

Adult↗

Incidence of colorectal cancer and all cause mortality in non-selected patients with ulcerative colitis and indeterminate colitis in Malmö, Sweden.

Cancer morbidity and all cause mortality were studied prospectively in all patients with definite and probable ulcerative colitis and indeterminate colitis diagnosed from 1958 to 1982, in the city of Malmö, Sweden. The follow-up to Jan. 1, 1990 was complete for all but ten patients. Nine of the 471 patients with ulcerative colitis and three of the 100 patients with indeterminate colitis developed colo-rectal cancer. The incidence of colorectal cancer in ulcerative colitis was 1.4 per 1000 person-years. The observed number of cases was 2.1 times higher than expected; (95% C.I. 1.0-4.1), based on the age- and sex-specific cancer incidence in the city during the study period. Indeterminate colitis was associated with a higher colorectal cancer risk than ulcerative colitis; 2.4 per 1000 person-years; (SMR 8.6, 95% C.I. 1.8-25.1). Both conditions were associated with a slight increased mortality rate, for ulcerative colitis 12.6 per 1000 person-years; (SMR 1.3, 95% C.I. 1.0-1.5), and for indeterminate colitis 11.7 per 1000 person-years; (SMR 2.7, 95% C.I. 1.6-4.4). Complications of colitis were the main cause of death in both groups. The cancer risk was related to extent of disease, duration of disease and female gender. Ten out of the 12 cases with cancer had or developed total colitis. However, only seven of the 134 cases with total ulcerative colitis and two of 87 cases with total indeterminate colitis developed cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Histological classification of the neoplastic changes arising in ulcerative colitis: a new proposal in Japan.

Patients with total ulcerative colitis with a longstanding course of the disease have a high risk of developing colorectal carcinoma. Colonoscopic surveillance to detect precancerous tissue and/or cancer in these patients has been carried out in countries with a high incidence of ulcerative colitis. Riddell's classification has been widely used for the interpretation of biopsy specimens obtained from the colonoscopic surveillance. In Japan, however, there are problems in accepting Riddell's classification, mainly because the intramucosal carcinomas diagnosed by Japanese histopathologists are included in the category of high-grade dysplasia in Riddell's classification. Based on the results of a meticulous slide review carried out by seven histopathologists in this study, a new classification is proposed: UC-I, inflammatory change; UC-II, indefinite; UC-IIa, probably inflammatory; UC-IIb, probably neoplastic; UC-III, neoplastic but not carcinomatous; and UC-IV, carcinoma. Intramucosal carcinomas is included in the category UC-IV. We consider that the diagnosis of intramucosal carcinoma is to be made when there is a high grade of cytological and structural atypia consistent with carcinoma. Interobserver and intraobserver variability with this classification was acceptable. We believe this new classification will be widely use in cancer surveillance in ulcerative colitis in Japan.

Biopsy↗

The disease activity of ulcerative colitis and Crohn's disease.

The disease activity in ulcerative colitis and Crohn's disease was studied. Parameters found to reflect the disease activity were given scores from 1 to 4. The score obtained by a patient compared with the maximum scores gives the percentage disease activity. The regressions between the percentage disease activity and the ESR in ulcerative colitis and Crohn's disease were r=0.68 (p less than 0.001) and r=0.48 (p less than 0.001), respectively. The different activity parameters have different time response curves explaining the occasional slight correlation. The percentage disease activity represents the mean activity of the different parameters at a given time. It is proposed to define slight, moderate, and severe ulcerative colitis or Crohn's disease as percentage disease activity of less than 30, 30-70 and greater than 70 per cent, respectively.

Blood Sedimentation↗

Risk of congenital abnormalities in children born to women with ulcerative colitis: a population-based, case-control study.

OBJECTIVES: It has recently been suggested that maternal ulcerative colitis is associated with an almost 4-fold increased risk of congenital abnormalities in offspring. We therefore examined the risk of congenital abnormalities in children born to women with ulcerative colitis. METHODS: This was a case-control study within the Hungarian Case Control Surveillance of Congenital Abnormalities, 1980-1996, based on 22,843 newborn children or fetuses with congenital abnormalities and 38,151 children without any detected congenital abnormalities (the control group). RESULTS: Seventy-one pregnant women (0.3%) had ulcerative colitis in the case group and 95 (0.2%) in the control group. The adjusted overall risk for having a child with congenital abnormalities in women with ulcerative colitis was OR = 1.3 (95% CI = 0.9-1.8). The risk of limb deficiencies, obstructive urinary congenital abnormalities, and multiple congenital abnormalities was OR = 6.2 (95% CI = 2.9-13.1), OR = 3.3 (95% CI = 1.1-9.5), and OR = 2.6 (95% CI = 1.3-5.4), respectively. No association was found for cleft lip with or without cleft palate or cardiovascular defects. CONCLUSIONS: We found no significantly increased overall risk of congenital abnormalities in children born to women with ulcerative colitis. However, our results indicate an increased risk of some selected congenital abnormalities (limb deficiencies, obstructive urinary congenital abnormalities, and multiple congenital abnormalities). More data are needed to determine whether the association between maternal ulcerative colitis and an increased risk of certain congenital abnormalities is causal or is influenced by bias.

Abnormalities, Multiple↗

Colonic motility and transit in health and ulcerative colitis.

Preprandial and postprandial colonic motility and transit (scintigraphy), with respect to the splenic flexure, were studied in 10 patients with ulcerative colitis and in 9 healthy subjects. The healthy subjects had a postprandial increase in intraluminal pressure that was significantly (P less than 0.03) greater in the descending colon than in other regions of the colon. In ulcerative colitis, the pressure was decreased in all regions compared with healthy subjects, with no significant pressure gradient among different regions. In normal subjects, transit was quiescent during fasting; eating stimulated both antegrade and retrograde transit. In ulcerative colitis, transit was variable before as well as after the meal. Both healthy subjects and patients with ulcerative colitis had more rapid emptying from the splenic flexure into the sigmoid than into the transverse colon. More frequent, low-amplitude, postprandial propagating contractions occurred in ulcerative colitis (P less than 0.05) than in healthy subjects. Propagating contractions were always antegrade and caused a rapid movement of the tracer into the sigmoid. In conclusion, ulcerative colitis is characterized by (a) decreased contractility, (b) increased low-amplitude propagating contractions, and (c) variable transit. These disturbances may accentuate the diarrhea in ulcerative colitis.

Adult↗

Mucosal enzyme activity for butyrate oxidation; no defect in patients with ulcerative colitis.

BACKGROUND: Butyrate is an important energy source for the colon and its metabolism has been reported to be defective in ulcerative colitis. One mechanism for defective butyrate metabolism in patients with ulcerative colitis could be an enzyme deficiency in the beta-oxidation pathway of butyrate. AIMS: This study was undertaken to measure the activity of each enzyme involved in the beta-oxidation pathway of butyrate in colonic epithelium. PATIENTS: Patients with ulcerative colitis (n = 33), Crohn's colitis (n = 10), and control subjects with colorectal cancer or diverticular disease (n = 73) were studied. METHODS: Analysis was carried out using fluorometric and spectrophotometric techniques on homogenised epithelial biopsy specimens. RESULTS: Significantly increased butyryl CoA dehydrogenase activity was found in mucosa from patients with ulcerative colitis (33.2 (28.3, 38.1) mumol/g wet weight/min:mean (95% CI)) compared with activity in mucosa from control patients (24.3 (20.9, 27.7) mumol/g wet weight/min:mean (95% CI)) p < 0.02. No significant increase in activity of the enzymes butyryl-CoA synthetase, crotonase or hydroxybutyryl-CoA dehydrogenase was found in patients with ulcerative colitis. In contrast the mucosal thiolase activity was significantly lower in those patients with quiescent colitis (3.21 (2.61, 3.81) mumol/g wet weight/min:mean (95% CI)) when compared with control mucosa (5.69 (5.09, 6.29) mumol/g wet weight/min:mean (95% CI)) p < 0.001. However, mucosal thiolase activity increases with the age of the donor patient and differences in the age range of the patient groups probably account for this finding. CONCLUSIONS: This study shows no substantial deficiency of enzyme activity in the beta-oxidation pathway of butyrate in the mucosa of patients with ulcerative colitis in histological remission.

Adolescent↗

Azathioprine hypersensitivity reaction in a patient with ulcerative colitis.

OBJECTIVE: To describe a case of azathioprine hypersensitivity in a patient with ulcerative colitis. CASE SUMMARY: A 40-year-old white man with ulcerative colitis, treated with chronic mesalamine and occasional steroids, was admitted to the hospital with a 3-day history of fever, nausea, vomiting, and a rash. Fourteen days prior to admission, the patient had been started on azathioprine for ulcerative colitis. Upon admission, azathioprine therapy was temporarily withheld, resulting in resolution of his signs and symptoms. Symptoms returned when azathioprine was restarted. It was decided that these signs and symptoms were most likely caused by azathioprine hypersensitivity, and the agent was discontinued. DISCUSSION: To our knowledge, this is the first reported case of azathioprine hypersensitivity in a patient with ulcerative colitis. The time course and presenting signs and symptoms support the diagnosis of azathioprine hypersensitivity, as does the patient's response to rechallenge. The mechanism of this hypersensitivity reaction is unclear, but may involve the nitroimidazole portion of the azathioprine molecule. CONCLUSIONS: Azathioprine hypersensitivity often presents with signs and symptoms resembling a systemic infection such as fever, leukocytosis, and evidence of end organ dysfunction. The diagnosis of azathioprine hypersensitivity should be considered in patients who have recently either initiated or increased their dosage of azathioprine.

Adult↗

Aquaporin expression is downregulated in a murine model of colitis and in patients with ulcerative colitis, Crohn's disease and infectious colitis.

Colitis is associated with alterations in electrolyte and water transport. These changes give rise to some of the symptoms experienced by patients with colitis. Alterations in fluid flux may also contribute to increased susceptibility to mucosal injury. Recently, endogenous water channel proteins (aquaporins; AQPs), have been identified in colonic tissue. The expression of AQP4, AQP7 and AQP8 was examined, via reverse transcription/polymerase chain reaction, Western blotting and immunohistochemistry, in a murine model of colitis and in patients with inflammatory bowel disease or infectious colitis. Colitis was induced in C57BL/6 mice by the addition of 2.5% dextran sodium sulphate (DSS) to their drinking water. AQP expression in these mice was assessed following 12 h to 7 days of DSS exposure and during the recovery phase from 1 to 15 days following cessation of DSS exposure. Colonic water transport was measured after 1 and 3 days of DSS and following 7 days of recovery. The expression of AQP4 and AQP8 mRNA was significantly decreased after 12-24 h of DSS exposure and remained depressed throughout the treatment period. Expression of AQP7 was more variable. Protein expression followed a similar pattern to that observed for AQP mRNA. Significant alteration in colonic fluid secretion was correlated with reduced expression of AQP isoforms. Significantly, patients with active ulcerative colonic, Crohn's colitis or infectious colitis had similar dramatic reductions in AQP expression that appeared to be correlated with disease activity. Thus, colonic injury in both mouse and man is associated with a downregulation in AQP expression.

Animals↗