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Progression of primary biliary cirrhosis after proctocolectomy for ulcerative colitis.

We report a case of progression of primary biliary cirrhosis (PBC) after proctocolectomy for ulcerative colitis. A 43-year-old woman underwent a total proctocolectomy after being diagnosed with ulcerative colitis. In the course of the preoperative investigation, liver function test results were within the normal range. Four months after the proctocolectomy, the patient showed a high level of alkaline phosphatase (2398 IU/l) and a positive anti-mitochondrial antibody titer (>1:160). There were no associated symptoms. A liver biopsy demonstrated expansion of all portal areas by infiltrates of lymphocytes and histiocytes. These appearances indicated chronic biliary disease and were compatible with PBC. The association of PBC and ulcerative colitis is rare. However, a review of the recent literature suggests that PBC and ulcerative colitis may be associated; this combination should be kept in mind.

Adult↗

Anti-colon antibody and lymphocytophilic antibody in ulcerative colitis.

The presence of anti-colon antibody in the sera from patients with ulcerative colitis was demonstrated by antibody-dependent cell-mediated cytotoxicity (ADCC) assay. In addition, the high prevalence of lymphocytophilic antibody in the sera from patients with ulcerative colitis was obtained by fluorescence activated cell sorter (FACS) analysis. This lymphocytophilic antibody was absorbed by rat colon epithelial cells. Moreover the lymphocytes from ulcerative colitis showed lower binding capacity to this antibody, but acquired higher binding capacity after 20 hr incubation at 37 degrees C in vitro. These data suggest that ADCC may have some role in the pathogenesis of ulcerative colitis.

Antibodies↗

Autoimmune thyroid disease with ulcerative colitis.

Two cases of co-existing thyroid disease and ulcerative colitis are reported. Thyroid disorder preceded ulcerative colitis in each case. The presence of acute colitis delayed and obscured the clinical diagnosis of thyrotoxicosis in one case and the colitis could not be controlled until her thyrotoxicosis was treated. Although the specific factors involved in this relationship are now known, an interplay of immunological factors is most probable.

Adult↗

Adoptive transfer of immune enhancement of experimental ulcerative colitis.

Previous experiments with the carrageenan model for ulcerative colitis have shown that the inflammatory response in guinea pigs can be enhanced by immunization with and subsequent feeding of Bacteroides vulgatus to experimental animals. The present studies showed that only certain strains of B. vulgatus are capable of provoking immune enhancement of ulcerative colitis. Animals were fed carrageenan and various strains of viable B. vulgatus after immunization with a strain of B. vulgatus isolated from a guinea pig with experimentally induced colitis. Histological comparison of immune and nonimmune groups revealed that immune animals which received B. vulgatus from a patient with inflammatory bowel disease had a significantly (P less than 0.025) greater number of histopathological lesions at 21 days than did nonimmune animals. Immune animals receiving B. vulgatus isolated from a clinically normal source did not show any significant difference in disease status when compared to nonimmune animals. Additional experiments showed that adoptive transfer of spleen cells from animals immunized with B. vulgatus to nonimmune recipient animals is effective in transferring the immune enhancement demonstrated in actively immunized animals. Animals which received immune spleen cells with concurrent feeding of B. vulgatus showed a significant (P less than 0.005) increase in inflammation over control groups, in the absence of high titers of circulating antibody. These experiments indicate that B. vulgatus strain-specific factors are important to immune enhancement of experimental disease and also suggest an involvement of the cell-mediated immune system in this model.

Animals↗

Ki-67: a useful marker for the evaluation of dysplasia in ulcerative colitis.

AIMS: Evaluation of dysplasia in long standing ulcerative colitis is a difficult and often subjective task. Therefore, the aim of this study was to search for a more objective parameter to help distinguish regenerative changes from epithelial dysplasia. METHODS: A total of 97 sections from colectomy specimens from 12 patients with ulcerative colitis of more than 10 years duration were stained immunohistochemically with MIB 1 to detect differences in the frequency and pattern of nuclei positive for the proliferation marker Ki-67. All patients had epithelial dysplasia in one or more areas (high grade dysplasia, n = 16; low grade dysplasia, n = 15; indefinite for dysplasia, n = 16), and three patients had additional adenocarcinoma (one Dukes's C multifocal, mucinous carcinoma; one Dukes's C adenocarcinoma in the sigmoid; and one Dukes's A adenocarcinoma in the caecum). Two patients had adenomas--one had an 8 cm villous adenoma with intramucosal carcinoma, and the other had a 4 cm tubulovillous adenoma with high grade dysplasia. RESULTS: There were highly significant differences between the percentages of Ki-67 immunopositive cells in low grade and high grade dysplasia and carcinoma compared with regenerative epithelium. In high grade dysplasia and carcinoma, the distribution of Ki-67 positive cells was diffuse throughout the full length of the crypt, whereas low grade dysplasia and epithelium indefinite for dysplasia, as well as regenerative epithelium, showed an expanded basal zone. CONCLUSIONS: Assessment of the number of Ki-67 immunostained cells is of additional value in deciding whether the mucosa is regenerative or dysplastic, and the MIB 1 staining pattern is characteristic for most lesions with high grade dysplasia and carcinoma. Therefore, this technique could be combined with routine histological evaluation of colorectal epithelium being examined for dysplasia.

Adenocarcinoma↗

Prevalence and family risk of ulcerative colitis and Crohn's disease: an epidemiological study among Europeans and south Asians in Leicestershire.

The family history of patients identified during incidence studies in Leicestershire were investigated and the prevalence and comparative risks calculated; 1254 patients aged 15 to 80 years were sent a questionnaire about their family history. All cases with a positive family history were reviewed and confirmed cases included in the study. In Europeans the standardised prevalence of Crohn's disease was 75.8/10(5) and that of ulcerative colitis 90.8/10(5). The prevalence of Crohn's disease among South Asians was 33.2/10(5) and that of ulcerative colitis 135/10(5). The prevalence of Crohn's disease in Europeans was significantly greater than that in Hindus (chi 2 = 16, p < 0.001), while the prevalence of ulcerative colitis was significantly lower in Europeans than Hindus (chi 2 = 27, p < 0.001) and Sikhs (chi 2 = 4.4, p < 0.05). The comparative risk of developing ulcerative colitis in first degree relatives of Europeans patients with ulcerative colitis was increased by approximately 15, but the risk of Crohn's disease was not increased. The comparative risk of developing Crohn's disease among first degree relatives of patients with Crohn's disease was increased by up to 35, the comparative risk of ulcerative colitis was approximately 3. The risk among relatives of South Asian patients with Crohn's disease was not increased, but the risk of ulcerative colitis to relatives of patients with ulcerative colitis was. This study supports the view that Crohn's disease and ulcerative colitis arise in people with a genetic predisposition and exposed to some, as yet unknown, environmental factor.

Adolescent↗

Comparative pharmacokinetics of sulphasalazine and sulphapyridine after rectal and oral administration to patients with ulcerative colitis.

Rectal administration of sulphasalazine to patients with ulcerative colitis has recently been shown to have similar therapeutic activity but fewer side effects than oral treatment. The present study is a comparison of the pharmacokinetics of sulphasalazine (SASP) and its metabolite sulphapyridine (SP) after rectal and oral administration of SASP to 6 patients with ulcerative colitis. The areas under the concentration-time curves (AUC) and the maximum concentrations (Cmax) of SASP and SP were significantly lower after rectal than oral administration of SASP (p less than 0.05). These findings support the view that the lower frequency of side effects after rectal administration of SASP may result from the lower plasma levels of SASP and SP.

Administration, Oral↗

[Comparison of salicylazosulfapyridine bioavailability following oral and rectal administration in patients with ulcerative colitis].

Salicylazosulfapyridine--a drug commonly used in the ulcerative colitis--is effective following both oral and rectal administration. Pharmacokinetics of the drug given per rectum (in the form of suppositories) has not been investigated so far. The present study aims at comparing bioavailability of salicylazosulfapyridine following oral and rectal administration to patients with the ulcerative colitis and healthy volunteers. It was found, that following rectal administration the drug is not so readily absorbed as in oral dosage form. No sulfapyridine and 5-aminosalicylic acid have been detected in blood serum, when the drug was given in the form of rectal suppositories. Clinical stage of the disease did not affect absorption of both unchanged drug and its metabolites. Due to the fact, that the drug is active locally, rectal suppositories seem a therapeutical alternative in patients only with lesions localized in the rectum.

Administration, Oral↗

Ornithine decarboxylase in colonic mucosa from patients with moderate or severe Crohn's disease and ulcerative colitis.

Polyamines, as well as ornithine decarboxylase (ODC), the enzyme involved in their synthesis, were reported to be closely related to cell proliferation. In Crohn's disease and ulcerative colitis, cell destruction and proliferation increase in the active stage. The aim of the present study was to determine the ODC in both involved and uninvolved areas of the colonic mucosa of active Crohn's disease and ulcerative colitis patients. The patients were divided in two groups, owing to the different level of activity (severe or moderate), by means of clinical endoscopy, laboratory, and histology evaluations. Subjects with suspected disease, but endoscopically unconfirmed, were used as controls. In all ulcerative colitis and Crohn's disease patients the ODC values both in involved and uninvolved mucosa were significantly lower than in controls. In severe Crohn's disease ODC was significantly reduced versus moderate Crohn's disease only in affected tissues. In all ulcerative colitis patients (moderate or severe) the ODC was significantly decreased in involved mucosa compared with uninvolved mucosa. Severe ulcerative colitis showed the significantly lowest ODC. We suggest that the significant decrease of ODC in the bowel mucosa is closely related to the severity of the disease. The highest decrease of ODC in ulcerative colitis patients would be due both to the enhanced cell destruction, and to the feed-back from exogenous increased polyamine production (bowel bacteria, cell desquamation). Therefore ODC would be considered a sensitive index of the inflammatory derangement of the mucosa, especially in acute ulcerative colitis. We conclude that this behaviour may result in an enhanced risk of neoplasia.

Adult↗

Density gradient centrifugation of colonic fluid after segmental lavage: a method of purification of exfoliative epithelial colonic cells for cytological interpretation and image cytometry in patients with long-standing ulcerative colitis.

OBJECTIVES: Patients with extensive, long-standing ulcerative colitis (UC) have an increased risk for developing colorectal cancer. In this study, we wanted to establish a method for retrieving cytological material after segmental colonic lavage for further cytopathological investigations and for performing DNA image cytometry. METHODS: Ten patients with long-standing and extensive ulcerative colitis and 10 patients without macroscopic abnormalities were investigated. After segmental colonic lavage during routine colonoscopy a three-layer (1.146, 1.075, and 1.046 g/ml, respectively) density gradient centrifugation of the retrieved colonic fluid was performed for isolation and purification of the epithelial cells. For identification of the epithelial cells flow cytometry with monoclonal antibody against cytokeratin and counterstaining with propidium iodine was performed. The smears obtained were stained for routine cytopathological interpretation and for DNA image cytometry. RESULTS: In eight of 10 UC patients and in nine of 10 control group patients adequate cytological material could be obtained. The band on top of the density gradient at 1.046 g/ml could be identified as the epithelial cells. Atypical cells were found in smears of three UC patients. In these patients and in one additional patient aneuploid stemlines could be detected. In smears of control group patients neither atypical cells nor aneuploidy were present. CONCLUSIONS: Isolation and purification of epithelial cells after segmental colonic lavage by using density gradient centrifugation was performed. This cytological material is adequate for cytopathological interpretation and for DNA image cytometry. Information about atypical cells and DNA aneuploidy as an additional marker of malignant transformation in UC patients was obtained. The combination of cytological examination and DNA image cytometry might improve the detection of UC patients with high risk for colorectal cancer.

Aneuploidy↗

Paracetamol metabolism in patients with ulcerative colitis.

AIMS: The capacity for sulphation of phenols appears to be impaired in the colonic mucosa of patients with ulcerative colitis. The aim of the present study was to investigate the systemic capacity for sulphation of phenols in patients with ulcerative colitis assessed by the metabolic clearances of paracetamol to the sulphate, glucuronide and glutathione derived metabolites. METHODS: Ten patients with ulcerative colitis and 10 control subjects received a single oral dose of paracetamol (1 g). Venous blood samples were collected frequently for pharmacokinetic determinations (one compartment model). Urine was collected for 24 h. Plasma samples were analysed for parent drug and urine samples for parent drug and metabolites by h.p.l.c. Partial metabolic clearances were calculated as the fractional urinary recovery of each conjugate multiplied by the apparent oral clearance of paracetamol. RESULTS: The apparent oral clearance of paracetamol and the partial clearances of its metabolites were not significantly different between the two study groups. Median value and the corresponding 25th and 75th percentiles for the clearance of the sulphate metabolites were 93.6 (82.5-138.8) ml kg(-1)h(-1) and 77.4 (75.5-99.1), patients with ulcerative colitis and control subjects, respectively. CONCLUSIONS: These results do not indicate a general impairment of the systemic capacity for sulphation of paracetamol in patients with ulcerative colitis.

Acetaminophen↗

Ultrastructure of colonic endocrine cells in ulcerative colitis.

Endoscopic specimens of colonic mucosa from 40 ulcerative colitis patients were investigated. Specimens were taken from both sexes patients, aged 16-74 (means = 41 years). An average number of 5 biopsies was examined in each patient taken 10, 20, 40, 50 and 80 cm from rectum. Material was divided into 3 groups: 1. histologically confirmed ulcerative colitis (CU), 2. clinical diagnosis of CU in remission-histologically non specific inflammation, 3. functional disorders of the large bowel-histologically normal colonic mucosa. The latter was a control group. Biopsies were fixed in glutaraldehyde, postfixed in osmium tetroxide. Ultrastructural examination was performed on Epon sections in Tesla BS-500 electron microscope operating at 60 kV. A Lausanne classification of endocrine cells was used in the study. The most common were EC cells, followed by PP, D1 and L respectively. In the first group of patients damaged endocrine cells were more commonly observed. These destructive changes were: vacuolisation of cytoplasm, degranulation and discharge of endocrine granules into intercellular space and degradation of the entire cells.

Adolescent↗

Living with ulcerative colitis.

This pilot study was undertaken to describe the experience of living with ulcerative colitis. Using a phenomenological approach, three subjects with diagnosed ulcerative colitis were interviewed and asked to describe what it was like to live with ulcerative colitis. Data from transcriptions of the audiotaped interviews were gathered and analyzed. Five major themes arose: the uncertainty surrounding exacerbations; the fear and humiliation surrounding stool incontinence; the desperate need to find successful treatment; the profound effect on family life, social life, and work; and, finally, the feeling of being controlled by the disease. Findings detail the impact of the disease on the subjects' lives and provide insight into this devastating disease. Implications for nursing practice and research are discussed.

Adaptation, Psychological↗

Colorectal and extracolonic malignancy in ulcerative colitis.

In a review of 1248 cases of ulcerative colitis seen at the Cleveland Clinic that were followed up to 1984 (mean, 14.4 years), 82 patients (6.5%) were subsequently found to have colorectal cancer and 48 (3.8%) had extracolonic malignancy, 6 of them with associated colorectal cancer. Most patients with colorectal cancer were men (2:1), and had extensive (90%) and long-lasting colitis (10 years or more in 93% of cases; mean 18 years). Colitis was inactive before the diagnosis of cancer in 48%. Acute onset of the first attack was rare (7%), and the disease had a remittent course in 92%. The mean age at diagnosis of cancer was 43 years. The cumulative risk of colorectal cancer was significantly higher in patients with extensive colitis than in those with left-sided disease (P less than 0.0001: 11.9% vs. 1.8% at 20 years and 25.3% vs. 3.7% at 30 years). When comparing mean duration of disease, left-sided colitis (22 years) did not differ significantly from extensive disease. The tumor was multifocal in 13.5%, proximal to the splenic flexure in 44%, and poorly differentiated in 34% of the cases. The diagnosis was suspected clinically in 64% of cases. The prognosis of colorectal cancer in patients with ulcerative colitis appears to be similar to that in the general population. The cumulative 5-year survival rate was 54%. This study supports the concept that surveillance colonoscopy should be started after 8 to 10 years of extensive colitis and after 15 years of left-sided colitis. Among those with extracolonic malignancy, the incidence of bile duct carcinoma, leukemia, bone tumors, and endometrial cancer was significantly greater than expected (P less than 0.01), whereas that of lung cancer was significantly lower than expected (P less than 0.01).

Adolescent↗

Autoantibodies to molecular targets in neutrophils in patients with ulcerative colitis.

Autoantibodies against neutrophil granulocytes are frequently observed in patients with ulcerative colitis, but a precise description of the autoantigens involved is lacking. Therefore, sera from 75 patients with ulcerative colitis were studied for antibody specificities by means of indirect immunofluorescence microscopy, enzyme-linked immunosorbent assays, and immunoblotting of extracts of neutrophils, neutrophil granules and lymphocytes. Fifty-six percent of the sera reacted in indirect immunofluorescence with ethanol-fixed neutrophils. On formalin-fixed cells most sera shifted fluorescence pattern, indicating a cytoplasmic origin of antigen(s). Only a few sera reacted with specific, known antigens. Immunoblots showed reactions with a broad panel of antigens with preferences for proteins around 55-65 kDa, which were present in azurophilic granules and in cytosol, an 80-kDa protein found in the specific granules, and a 110-kDa unknown cytosol component. In conclusion, neutrophil-specific IgG autoantibodies from ulcerative colitis patients react with several different antigens, most of which are of nonnuclear origin.

Autoantibodies↗

A case presentation of hemolytic anemia in ulcerative colitis and review of the literature.

Autoimmune hemolytic anemia associated with ulcerative colitis is a rare occurrence, and its management poses a therapeutic dilemma. Herein we present a case of ulcerative colitis involving an autoimmune hemolytic anemia and discuss the proposed mechanisms for the anemia. A review of past reported cases and their outcomes is included. In the past, a patient with autoimmune anemia unresponsive to corticosteroids was subjected first to splenectomy and then to colectomy if splenectomy failed to resolve the anemia. In view of the high failure rate for splenectomy, we recommend that ulcerative colitis patients with anemia unresponsive to corticosteroids proceed directly to total colectomy.

Adult↗

Clinical and urinary characteristics of urolithiasis in ulcerative colitis.

In a group of 112 patients with ulcerative colitis, eight patients (7.1%) developed the complication of urolithiasis. A higher incidence was found in those with total colitis (15.4%) and in postoperative patients (20%). The mean period between the onset of colitis and the initial urinary symptoms was 5.4 yr. All the analyzed stones contained oxalate and seven of eight patients had hyperoxaluria, which was believed to be one of the important lithogenic factors. Increased urinary Ca/Mg ratio, steroid, and sulfasalazine are suggested as the other lithogenic factors in patients with ulcerative colitis.

Adult↗

Ulcerative colitis and pregnancy.

A survey has been made of pregnancy occurring in patients who were attending the Ulcerative Colitis Clinic at Oxford during the 20-year period, 1960-79 inclusive. There were 256 married women of child-bearing age who attended during this period. Of these, 100 were excluded from the survey for various reasons, such as that they had completed their family before the onset of the ulcerative colitis, had already had an hysterectomy, or had a proctocolectomy before their first pregnancy. Of the remaining 156 patients, nine could not be traced. Full details were obtained from 147 patients, virtually all of whom were interviewed. The fertility of these patients was normal. Of the 147 women, 119 (81%) had conceived and only 10 (6.8%) were involuntarily infertile. The size of family approximated to that found in the general British population. The overall outcome of the pregnancies was similar to that in the general British population. The patients in whom the disease was quiescent at the start of pregnancy fared particularly well. Those with active disease had a somewhat lower chance of producing a normal live baby. The small group of patients in whom the disease was severe had a much lower chance of a normal outcome. Patients in whom the ulcerative colitis was quiescent at the beginning of pregnancy had a good chance of remaining symptom-free throughout the pregnancy and puerperium. Even if the colitis recurred, it was likely to be mild and responsive to medical treatment. By contrast, when the ulcerative colitis was active at the start of pregnancy, most patients continued to have symptoms in spite of medical treatment. Some patients had their first attack of ulcerative colitis during pregnancy or the puerperium. In contrast to previous experience the attacks were generally mild and responded to medical treatment. Medical treatment with corticosteroids or sulphasalazine appeared to have no obvious deleterious effects on the fetus or new-born child.

Adrenal Cortex Hormones↗