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Familial occurrence of primary sclerosing cholangitis and ulcerative colitis.

Members of three families had primary sclerosing cholangitis and chronic ulcerative colitis. In each family, two siblings were affected; in one instance, they were twin brothers. All six individuals had primary sclerosing cholangitis and five also had ulcerative colitis. These cases represent the first reported instances of the familial occurrence of both primary sclerosing cholangitis and chronic ulcerative colitis; illustrate the typical clinical, laboratory, radiologic, and pathological features of primary sclerosing cholangitis; and support the hypothesis that genetic factors may play a role in the etiology of this obscure disorder.

Adolescent↗

Multicentric colonic lymphoma complicating ulcerative colitis.

A 72-year-old female with ulcerative colitis of 30 years duration underwent total proctocolectomy for a cecal mass thought to be an adenocarcinoma. Pathologic examination of the colon revealed 22 tumors, all of which proved to be malignant lymphoma, histiocytic type. Thirteen cases of non-Hodgkins malignant lymphoma and 2 cases of Hodgkins disease of the colon arising in ulcerative colitis are reviewed and discussed.

Aged↗

Randomised controlled trial of azathioprine and 5-aminosalicylic acid for treatment of steroid dependent ulcerative colitis.

BACKGROUND AND AIMS: There are limited evidence based data concerning the use of azathioprine in ulcerative colitis. We aimed to compare the efficacy of azathioprine and oral 5-aminosalicylic acid in inducing remission of steroid dependent ulcerative colitis. METHODS: Seventy two patients with steroid dependent ulcerative colitis were admitted to this investigator-blind study. Steroid dependence was defined as a requirement for steroid therapy > or =10 mg/day during the preceding six months, with at least two attempts to discontinue the medication. The disease had to be clinically and endoscopically active at study entry, and all patients were taking systemic prednisolone (40 mg/day). Patients were randomised to receive azathioprine 2 mg/kg/day or oral 5-aminosalicylic acid 3.2 g/day, for a six month follow up period. The outcome of the treatment was defined as (1) success, indicating induction of clinical and endoscopic remission and steroid discontinuation, or (2) failure, indicating the absence of clinical and endoscopic remission and therefore the need for at least one further cycle of systemic steroids to control symptoms, apart from the initial one, or colectomy. RESULTS: Significantly more patients in the azathioprine than in the 5-aminosalicylic acid group had clinical and endoscopic remission, and discontinued steroid therapy, both in the intention to treat (azathioprine v 5-aminosalicylic acid: 19/36 patients (53%) v 7/36 (21%); odds ratio (OR) 4.78 (95% confidence interval (CI) 1.57-14.5)) and per protocol (azathioprine v 5-aminosalicylic acid: 19/33 patients (58%) v 7/34 (21%); OR 5.26 (95% CI 1.59-18.1)) analysis. CONCLUSIONS: Azathioprine is significantly more effective than 5-aminosalicylic acid in inducing clinical and endoscopic remission and avoiding steroid requirement in the treatment of steroid dependent ulcerative colitis.

Adolescent↗

The medical management of acute and chronic ulcerative colitis.

The current medical therapy of severe, acute ulcerative colitis is reviewed. The role and of 5-ASA, corticosteroids, immunosuppressive agents and surgery are outlined. A systematic approach using a combination of these agents to induce a remission is presented. A model for long term maintenance therapy following a response in the acute setting to avoid steroid dependence and surgery is proposed. The role of surgery in ulcerative colitis should be limited to patients who either fail medical therapy or in whom dysplasia or cancer have been detected. A realistic assessment of the potential pitfalls of surgical intervention, such as ileal pouch-anal anastomosis, is discussed.

Acute Disease↗

[Surgical therapy of Crohn disease and ulcerative colitis].

Surgical treatment of Crohn's disease and ulcerative colitis is standardized today, despite several unresolved problems. Cooperation between gastroenterologist and surgeon is essential to establish the indication for surgery in emergency situations and during the chronic phase, as well. The surgical procedures aim for maximum preservation of function; in Crohn's disease salvage of bowel by means of limited resections and strictureplasty has priority, whilst in ulcerative colitis the preservation of sphincter function is the paramount goal, wherever possible, by means of ileorectostomy and ileal pouch procedures.

Anal Canal↗

Increased rectal wall thickness may predict relapse in ulcerative colitis: a pilot follow-up study by ultrasonographic colonoscopy.

BACKGROUND AND STUDY AIMS: Ulcerative colitis is a chronic inflammatory bowel disease with repeated remission and relapse, although the occurrence of relapse is difficult to predict. We performed a prospective study to determine whether there is a relationship in ulcerative colitis between the inflammatory changes identified by endoscopic ultrasonography (EUS) and relapse. PATIENTS AND METHODS: Participants were 23 ulcerative colitis patients who had not suffered a relapse for 1 month, with a Seo activity index less-than-or-equal 150 and Baron grade 1 at colonoscopy. The thickness of the first to the third layer of the rectal wall in these patients was measured by EUS at the start of the study. They were subsequently followed up for 1 year to record any relapses, defined as having a Seo activity index > 150 and Baron grade greater-than-or-equal 2 at colonoscopy. RESULTS: Relapse occurred in eight patients. The mean activity index of the relapsed patients was 187.3 (95 % confidence interval (CI), 166.4 - 208.2) at the end of the study. The thickness of the first to the third layer of the rectal wall, as evaluated by EUS at the beginning of the study, was significantly larger in the relapse group (mean 2.73 mm, 95 % CI 2.13 - 3.33 mm) than in the non-relapse group (1.79 mm; 1.56 - 1.99 mm; P = 0.0001). CONCLUSIONS: Catheter probe-assisted endoluminal ultrasonography may predict the occurrence of relapse of ulcerative colitis.

Adult↗

Interleukin 1beta-induced production of H2O2 contributes to reduced sigmoid colonic circular smooth muscle contractility in ulcerative colitis.

We have shown that neurokinin A-induced contraction of human sigmoid circular muscle (HSCM) is reduced in patients with ulcerative colitis and that interleukin (IL)-1beta may play a role in this change. We now examine changes in the signal transduction pathway mediating neurokinin A-induced contraction of HSCM and explore the role of IL-1beta and of H(2)O(2) in these changes. In Fura 2-AM-loaded ulcerative colitis HSCM cells, neurokinin A- and caffeine-induced peak Ca(2+) increase and cell shortening were significantly reduced. In normal cells, neurokinin A-induced contraction was decreased by protein kinase C inhibitor chelerythrine and by calmodulin inhibitor CGS9343B [1,3-dihydro-1-[1-[(4-methyl-4H,6H-pyrrolo[1,2-a][4,1]-benzoxazepin-4-yl)methyl]-4-piperidinyl]-2H-benzimidazol-2-one (1:1) maleate]. In ulcerative colitis muscle cells, contraction was inhibited only by chelerythrine but not by CGS9343B. IL-1beta treatment of normal HSCM strips and cells reproduced the changes observed in ulcerative colitis. IL-1beta-induced reduction in caffeine-induced peak Ca(2+) increase and contraction was reversed by catalase, suggesting a role of H(2)O(2). IL-1beta-induced H(2)O(2) production was inhibited by mitogen-activated protein kinase (MAPK) kinase inhibitor PD98059 (2'-amino-3'-methoxyflavone) and by cytosolic phospholipase A2 (cPLA(2)) inhibitor AACOCF3 (arachidonyltrifluoromethyl ketone), but neither by p38 MAPK inhibitor SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole] nor by nuclear factor-kappaB (NF-kappaB) inhibitory peptide NF-kappaB SN50 (H-Ala-Ala-Val-Ala-Leu-Leu-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Val-Gln-Arg-Lys-Arg-Gln-Lys-Leu-Met-Pro-OH). IL-1beta significantly increased the phosphorylation of extracellular signal-regulated kinase 1 (ERK1)/ERK2 MAPKs and cPLA(2) and IL-1beta-induced cPLA(2) phosphorylation was blocked by PD98059. We conclude that Ca(2+) stores of HSCM cells may be reduced in ulcerative colitis and that the signal transduction pathway of neurokinin A-induced contraction switches from calmodulin- and protein kinase C-dependent in normal cells to protein kinase C-dependent in ulcerative colitis cells. IL-1beta reproduces these changes, possibly by production of H(2)O(2) via sequential activation of MAPKs (ERK1/ERK2) and cPLA(2).

Calcium↗

Extraintestinal manifestations of idiopathic ulcerative colitis.

One hundred and fifty patients of idiopathic ulcerative colitis were studied for extraintestinal manifestations by clinical, radiological and biochemical means. One or more such manifestations occurred in 34.7% of patients. Sacroiliitis (14%) and peripheral arthritis (10.7%) were the commonest manifestations, followed by ocular (8%), mucocutaneous (2.7%), vascular (2%) and hepatobiliary (1.3%) manifestations. We conclude that the incidence and spectrum of extraintestinal manifestations in Indian patients with idiopathic ulcerative colitis are similar to those in western patients.

Adolescent↗

Xanthine oxidase activity is not increased in the colonic mucosa of ulcerative colitis.

AIM: To measure urate and xanthine by high-performance liquid chromatography in mucosal biopsies from patients with ulcerative colitis and controls. RESULTS: Reactive oxygen metabolite activity was demonstrated by a cystine to cysteine ratio of 0.24 +/- 0.08 in the control biopsies compared with 1.79 +/- 0.25 in ulcerative colitis. The product to substrate ratio (urate to xanthine) for xanthine oxidase and mucosal urate concentrations were not different between ulcerative colitis patients and controls. Xanthine oxidase activity after incubation of homogenized biopsies was 0.451 (+/- 0.175) nmol.min/mg protein in ulcerative colitis patients compared with 2.585 (+/- 0.823) nmol.min/mg protein in controls (P < 0.01). CONCLUSION: These results suggest that xanthine oxidase may not be the major source of superoxide formation in ulcerative colitis.

Biopsy↗

Proctocolectomy and ileostomy for ulcerative colitis: the longer term story.

Elective surgery for ulcerative colitis usually involves the removal of the entire large bowel with either a conventional ileostomy or the formation of an ileoanal pouch anastomosis. Seventy patients undergoing a one stage elective total proctocolectomy and ileostomy between 1976 (the first year an ileoanal pouch was carried out in this hospital) and 1986 have been studied. We have confirmed that proctocolectomy and ileostomy for ulcerative colitis is not the trouble free operation many presume it to be when considering the alternative of an ileoanal pouch.

Adult↗

Deficiency of epithelial basement membrane laminin in ulcerative colitis affected human colonic mucosa.

Imbalances in epithelium-matrix interactions have been discussed as a pathomechanism in ulcerative colitis, causing a colonic mucosal barrier dysfunction. Laminin, the major noncollagenous component of the basement membrane, plays a role in epithelial basal lamina formation and promotes differentiation of human enterocytes. We therefore investigated the distribution of laminin in ulcerative colitis affected colonic tissues. Tissue specimens from both affected and nonaffected colonic regions were obtained from ten patients with ulcerative colitis during colonoscopies or operations. Healthy tissue from five patients with colorectal cancer was used as control. After histological classification, the localization and distribution of the basement membrane associated extracellular matrix proteins were determined by immunohistochemistry. Paraffin-embedded sections were incubated with antibodies against laminin and type IV and V collagen. No positive immunoreactivity against laminin was found in most of the epithelial basement membranes surrounding the crypts in affected colonic tissues, without involvement of the subendothelial structures. In contrast, a type IV and V collagen accumulation occurred in all these tissue samples. The lack of laminin in combination with an overexpression of type IV and V collagen, as reported for the first time in this paper, leads to changes in basement membrane structure. These findings indicate that the three-dimensional network of the colonic epithelial basement membrane and its function are seriously disturbed in exacerbating ulcerative colitis. This provides new insights into the importance of cell-matrix interactions for physiological and pathological mechanisms in the etiology of ulcerative colitis.

Adolescent↗

Lack of effect of antineutrophil cytoplasmic antibodies associated with ulcerative colitis on superoxide anion production from neutrophils.

BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCAs) from patients with vasculitidis can induce neutrophils to release oxygen radicals in vitro. ANCAs with a perinuclear pattern of immunofluorescence are found in most patients with ulcerative colitis, but several findings are against ANCAs having a pathogenetic role in this disease. AIMS: To evaluate the influence of ANCAs associated with ulcerative colitis on the respiratory burst activity of neutrophils. PATIENTS: Serum samples were obtained from 14 patients with ulcerative colitis, seven of whom showed positivity for p-ANCAs, three patients with vasculitidis, two with positivity for p-ANCAs, and one for c-ANCAs, and seven healthy volunteers. METHODS: A positive ANCA serology was determined with a standard indirect immunofluorescence assay. Purified immunoglobulins (IgGs) were prepared from serum samples by DEAE-Affigel blue chromatography. Human neutrophils were prepared by dextran-Ficoll-Hypaque separation. Superoxide anion (O2-.) generation was measured by following the superoxide dismutase inhibitable reduction of ferricytochrome. RESULTS: There were no significant differences among samples from ulcerative colitis IgG p-ANCA positive, ulcerative colitis IgG p-ANCA negative patients, and controls on O2-. production, whereas ANCA positive IgG from vasculitidis significantly enhanced O2-. release (p < 0.001). CONCLUSIONS: p-ANCAs associated with ulcerative colitis have no effect on the respiratory burst activity of normal human neutrophils in vitro. These results reinforce the hypotheses that ANCAs are unlikely to contribute to the pathogenesis of ulcerative colitis.

Antibodies, Antineutrophil Cytoplasmic↗

[Type I allergy and indices of immune response in patients with ulcerative colitis].

In a group of 24 patients with ulcerative colitis and in 15 persons in the control group allergological studies were carried out which included history taking, cutaneous tests, assessment of total concentration and presence of specific IgE in the serum, and selected immune response indices (Ig levels, immune complex concentration and numbers of T- and B-cells). In our studies it was found that in two-thirds of patients with ulcerative colitis clinical reactions after meal occurred, in 54% atopy coexisted, and immunological abnormalities occurred more frequently than in the control group. Our studies proved that the role of various reactions to consumed meal, including early allergic reactions, cannot be rejected with full certainty. A number of indirect evidence that type I allergy according to Gell and Coombs, and immunological abnormalities participated in the pathological mechanism of that disease was also found.

Adult↗

Bone mineral density and calcium regulating hormones in patients with inflammatory bowel disease (Crohn's disease and ulcerative colitis).

Inflammatory bowel disease (Crohn's disease and ulcerative colitis) is associated with decreased bone mineral density and increased risk of osteoporosis. However, the pathogenesis of this bone loss is not yet fully understood. In the present study we measured lumbar bone mineral density (by dual photon absorptiometry), serum levels of parathyroid hormone (PTH) and vitamin D metabolites, and serum markers of bone turnover (alkaline phosphatase and osteocalcin) in 15 patients with Crohn's disease and in 4 patients with ulcerative colitis. The median duration of the disease was 4 years and the median lifetime steroid dose was 10g of prednisone. We compared our results to a control group of 19 normal persons, who were matched for age and sex to the patients. We found that lumbar bone density was reduced by 11% in patients compared with control persons (Z-score -0.6 +/- 0.6 versus -0.1 +/- 0.8; p < 0.05). In patients, the serum levels of PTH, 25-hydroxyvitamin D3, and calcitriol (1,25(OH)2D3) were significantly reduced compared with control persons. Serum alkaline phosphatase activity (AP) was significantly higher in the patients and was inversely related to lumbar bone density. Osteocalcin values were not different between patients and control persons. There was also no difference in serum levels of calcium between the two groups, whereas phosphorus levels were higher in patients. We conclude that malabsorption of calcium was not a primary cause of bone loss in our patients, because we did not find secondary hyperparathyroidism. Accordingly, we did not find a severe vitamin D deficiency, since 25-hydroxyvitamin D3 levels were within the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Failure of right-sided coloanal anastomosis for treatment of left-sided ulcerative colitis. Report of a case.

A patient with ulcerative colitis limited to the rectum and distal colon underwent a left hemicolectomy, a mucosal proctectomy, and a coloanal sleeve anastomosis using the normal proximal colon. She experienced macroscopic recurrence of her disease within 2 months of the operation and eventually required excision of the remaining colon and an end ileostomy. Our experience and that of others would indicate that a right-sided coloanal operation is unsuitable for the treatment of left-sided ulcerative colitis.

Adult↗

Erosive temporomandibular joint disease as a feature of the spondyloarthropathy of ulcerative colitis.

A patient with ankylosing spondylitis associated with ulcerative colitis developed bilateral temporomandibular joint pain and severe restriction of jaw motion. Conventional radiographs did not show structural abnormality of the temporomandibular joints, but corrected axis tomography revealed erosions in both mandibular condyles with extensive reactive sclerosis in the subchondral bone. These findings suggest that the temporomandibular joint disease in this case was a feature of the patient's spondylitis rather than a manifestation of the peripheral joint arthritis which commonly occurs in patients with ulcerative colitis.

Adult↗

Oral hairy leukoplakia in a patient with ulcerative colitis.

A 30-year-old man with ulcerative colitis developed oral hairy leukoplakia (OHL). Serological examination for human immunodeficiency virus (HIV)-1 and HIV-2 infection showed no abnormalities. Biopsy specimen of the lateral tongue showed ballooned prickle cells, and electron microscopy revealed herpes-type viruses. Immunologic investigation of the patient showed a marked decrease in T-helper cells as a result of immunosuppressive regimen. The present report appears to be the first well-documented case of OHL in an HIV-negative patient with ulcerative colitis. OHL may be a marker for severe immunosuppression but is not necessarily associated with HIV infection. Patients with iatrogenic immunosuppression should be monitored for OHL. Concerning the marked decrease in T-helper cells in this case, the presence of OHL may imply the examination of T-lymphocyte subsets in patients such as HIV-infected individuals or in organ transplant recipients.

Adult↗

Controlled trial comparing olsalazine and sulphasalazine for the maintenance treatment of ulcerative colitis.

One hundred and sixty four patients with ulcerative colitis in remission were entered into a double blind, double dummy trial comparing olsalazine 500 mg bd and sulphasalazine 1 g bd. Clinical examination, sigmoidoscopy and rectal biopsy were performed at 0, three, and six months. Sixteen of 82 (19.5%) patients relapsed on olsalazine and 10/82 (12.2%) relapsed on sulphasalazine. The difference was not statistically significant (p = 0.1632). Adverse events were minor and were similar in both groups. No haematological or biochemical abnormalities were detected. Thus, olsalazine is as effective as sulphasalazine for preventing a relapse of ulcerative colitis.

Adolescent↗