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PubMed2002

Collagenous colitis associated with lansoprazole.

BACKGROUND: Collagenous colitis is a diarrheal illness of unknown cause. The purpose of this report is to describe a case of collagenous colitis related to lansoprazole exposure. STUDY: Case report. RESULTS: A patient is described who developed clinical and pathologic findings of collagenous colitis during treatment with lansoprazole and omeprazole. Symptoms of diarrhea and histopathologic abnormalities resolved after drug withdrawal and recurred with re-exposure to lansoprazole. CONCLUSIONS: The observations are compatible with collagenous colitis or lymphocytic colitis associated with exposure to lansoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2003

Verocytotoxin-producing Escherichia coli EH 0157:H7 colitis.

0157:H7 is a known etiologic agent of hemorrhagic colitis. The clinical and histologic picture of colitis is largely similar to that of ischemic colitis, with areas of submucosal hemorrhage and edema, erosions, and ulcerations. We present a case report and review of the literature. A 52-year-old HIV-positive man, in apparently good immunologic condition, developed severe hemorrhagic colitis characterized by the onset of multiple colonic perforations and an unfavorable outcome. The diagnosis of 0157:H7 colitis should therefore be considered in all patients with indeterminate hematic diarrhea. Further studies are warranted to verify whether HIV infection may play a determinant role in the clinical course of 0157:H7 infection.

Colitis↗

PubMed1994

Prospective evaluation of upper gastrointestinal mucosal lesions in children with ulcerative colitis and Crohn's disease.

Eighty-eight consecutive children with inflammatory bowel disease were studied, and upper gastrointestinal endoscopy was performed in 80 of them as one of the initial investigations before commencing medical or nutritional treatment. Forty-one children were found to have Crohn's disease and 47, ulcerative colitis. Upper gastrointestinal endoscopy revealed pathology in 32 (80%) cases of Crohn's disease, esophagitis in 16, and esophageal ulcer in two, nonspecific gastritis in 22, duodenitis or duodenal ulcer in 18, and Helicobacter pylori infection in two cases. Granulomas were detected in 10 patients in the upper gastrointestinal tract: one esophageal, eight gastric, and three duodenal. Of the ulcerative colitis patients, seven had esophagitis, one had esophageal ulcer, 17 had nonspecific gastritis, two had gastric ulcers, two had duodenal ulcers, and five had H. pylori infection; altogether 30 (75%) yielded pathological findings. Radiological studies using barium meal revealed pathology in only eight of all inflammatory bowel disease cases. Symptoms at admission were not conclusive for definite diagnosis because 63% of patients with Crohn's disease had signs of colitis (such as diarrhea, bloody diarrhea) compared to 94% of ulcerative colitis patients. Upper gastrointestinal endoscopy may be used to achieve a specific diagnosis, thus being helpful when planning treatment. Also a considerable incidence of nonspecific gastritis, duodenitis, and esophagitis with or without concomitant H. pylori infection may be anticipated in children suffering from both ulcerative colitis and Crohn's disease.

Child↗

PubMed2003

The relationship between the concentration of dextran sodium sulfate and the degree of induced experimental colitis in weanling rats.

BACKGROUND: Although a dextran sodium sulfate (DSS)-induced colitis is commonly used as an ulcerative colitis (UC) model in adult rodents, there are no studies using this model in young animals. We examined differences in the severity of DSS-induced colitis as a function of the concentration of DSS administered and sought to establish a DSS-induced colitis model in young rats. METHODS: We administrated different concentrations of DSS solution (2%, 3%, and 4%) to 4-week-old weanling rats and compared their clinical findings, colonic histologic findings, mucosal leukotriene B4 (LTB4) production, and mucosal blood flow with control weanling rats and 8-week-old adult rats given 4% DSS for induced colitis. RESULTS: Clinical symptoms, such as diarrhea and rectal bleeding, histologic findings, and disturbance of mucosal microcirculation in weanling rats given 4% DSS were significantly more severe than those in adult rats given the same treatment. Three of 10 rats given 2% DSS had no bloody stool and 2 of 10 rats given 4% DSS died during the experimental periods. Clinical symptoms, hemoglobin levels, histologic damage scores, mucosal LTB4 production, and mucosal blood flow became more severely deranged as the concentration of DSS increased from 2% to 4%. CONCLUSION: These findings suggest that we can adjust disease severity in UC model for young children by giving different concentrations of DSS to weanling rats.

Aging↗

PubMed1975

Colitis associated with clindamycin therapy.

Clindamycin (7-chloro-7-deoxylincomycin) may induce mild or severe colitis. In 28 months, clindamycin-associated diarrhea was encountered in 8 patients who had received oral therapy. Severe, acute colitis was seen in 4 older patients, 3 of whom had acute pseudomembranous colitis and one who had an adynamic ileus mimicking an acute abdomen. Mild colitis with protracted diarrhea occurred in 4 younger patients who had mild, nonspecific inflammation in the rectum which responded to symptomatic treatment. The mechanism and true incidence of diarrhea as a sequel of clindamycin therapy are unknown. In all 8 patients, the use of clindamycin was arbitrary. Because of potentially serious gastrointestinal disturbance, including acute pseudomembranous colitis, clindamycin should be reserved for anaerobic and other serious infections.

Adult↗

PubMed1997

Definition and diagnosis of cytomegalovirus colitis in patients infected by human immunodeficiency virus.

The definition and routine diagnosis of cytomegalovirus (CMV) colitis in patients infected by human immunodeficiency virus (HIV) are controversial. In 100 consecutive HIV-infected patients who underwent colonoscopy for the investigation of diarrhea, we compared the yields of routine diagnostic tools for CMV infection and assessed the risk of further CMV organ disease in subgroups of patients with the following features: full evidence of CMV colitis (group 1), colonic CMV infection but no endoscopic lesions (group 2), and no evidence of colonic CMV infection (group 3). All biopsies taken during colonoscopy were examined immediately by routine hematoxylin and eosin (H&E) staining and viral culture and then pooled for second-line H&E staining and immunohistology. Among the 15 diagnoses of CMV colitis (group 1), two were missed during initial H&E examination, and both patients developed further CMV organ disease during follow-up. Of the 12 group 2 patients 11 were not receiving anti-CMV drugs at the time of initial colonoscopy. CMV organ disease was not significantly more common in these patients than in group 3 during follow-up. We conclude that routine H&E staining of colonic biopsy specimens for CMV inclusions is not 100% sensitive for CMV colitis. The favorable outcome of colonic CMV infection without endoscopic lesions suggests that only patients with full evidence of CMV colitis warrant specific antiviral therapy.

Adult↗

PubMed1996

The topical treatment of distal ulcerative colitis.

In the absence of a definitively curative medical treatment of distal ulcerative colitis, the major objective of drug therapy is to optimize the quality of life by rapidly suppressing the symptoms of inflammation, without introducing major side effects. Conventional steroids administered topically decrease inflammation in about two-thirds of patients with active distal ulcerative colitis after 3-4 weeks of therapy. However, the risk of the systemic side-effects associated with their prolonged use discourages long-term treatment with these drugs. Enemas containing topically acting steroids are likely to replace conventional steroid enemas in the near future, especially in those patients who need long-term or high-dose therapy. The efficacy, safety and acceptance of rectal formulations of 5-aminosalicylic acid (5-ASA) in the short-term treatment of active ulcerative colitis are now well established. This 5-ASA enemas may be the best initial treatment when the disease is limited to the distal colon. Combination therapy of a topical corticosteroid with 5-ASA enema is a promising treatment for patients with active distal ulcerative colitis. Lignocaine, bismuth subsalicylate and short-chain fatty acids are new drugs under investigation with as yet unproven value. Better information concerning the natural history of the disease and a more careful definition of subgroups of patients may make it possible to personalize dosage, formulation and duration of the active medical treatment for patients with distal ulcerative colitis.

Administration, Topical↗

PubMed1996

Long-term therapy with sulphasalazine protects against colorectal cancer in ulcerative colitis: a retrospective study of colorectal cancer risk and compliance with treatment in Leicestershire.

OBJECTIVES: The aims of this study were to (i) estimate the prognosis of a 10-year cohort as expressed by risk of colectomy and risk of development of colorectal cancer, and (ii) assess the impact of long-term sulphasalazine on the natural course of ulcerative colitis. PATIENTS: One hundred and seventy-five patients diagnosed between 1972 and 1981 with either total colitis (n = 143) or with limited ulcerative colitis but deceased (n = 32) were identified. Overall there was 98% case ascertainment and verification. RESULTS: A total of 49 patients underwent a colectomy, 6 as emergency laparotomies, 36 for failed medical management and 7 for known colorectal cancer, giving a crude colectomy rate of 23.2%. The colectomy rate was 7.2% in the year of diagnosis, decreasing in frequency over the next 4 years, then reaching a steady state of approximately 1.7% per year. In the total cohort, colorectal cancer occurred in 10 patients within the study period. The cumulative incidence of colorectal cancer 10 years after diagnosis was 2.1% and at 20 years 7.4% for the total group of patients excluding those with a colectomy. The mean duration of ulcerative colitis before diagnosis was 7.9 years (range 5-12). The crude proportions developing cancer were 5/152 (3%) in the group who took long-term sulphasalazine but 5/16 (31%) in the those who had had their treatment stopped or who did not comply with therapy. This is highly significant using a simple chi 2 test (chi 2 = 20.2, df = 1, P < 0.001). Two methods were used for survival analyses, the log-rank and the generalized Wilcoxon methods. Both give highly significant values for the crude effect of compliance (P < 0.001). CONCLUSION: Patients with ulcerative colitis who were not on long-term sulphasalazine or 5-aminosalicylic acid therapy (either because a doctor stopped it or they did not comply with treatment) were significantly more likely to develop colorectal cancer than their compliant counterparts.

Adult↗

PubMed1997

The soluble interleukin-2 receptor as an indicator of clinical evolution in patients with ulcerative colitis.

BACKGROUND/AIMS: The soluble interleukin-2 receptor is a useful, non-specific marker of in-vivo activated cellular immune functions. The aim of this study was to evaluate the correlation between this marker and clinical evolution of ulcerative colitis. METHODS: Serum soluble interleukin-2 receptor levels were determined, by an enzyme immune assay, in 105 patients affected by ulcerative colitis with different extent and activity of disease. Forty-six of these patients were restaged in a follow-up study, and their serum-soluble interleukin-2 receptor concentrations were measured again. RESULTS: Serum soluble interleukin-2 receptor level is higher in pan-ulcerative colitis than in left ulcerative colitis (P = 0.050) and much higher in active than in quiescent stage of disease (P = 0.029). Clinical relapse of disease is accompanied by a serum soluble interleukin-2 receptor rise (P = 0.0697), whereas clinical and histological improvement in disease is accompanied by its significant decrease (P = 0.0009). CONCLUSION: In ulcerative colitis the serum determination of soluble interleukin-2 receptor is a useful and non-invasive marker of activity, and also extension and evolution of the disease.

Adult↗

PubMed1997

Treatment of extraintestinal complications of ulcerative colitis.

Extraintestinal complications affect 25-30% of patients with ulcerative colitis. These extraintestinal disorders significantly contribute to morbidity and mortality of ulcerative colitis patients. While some disorders parallel the activity of the colitis, other abnormalities run a clinical course independent of the bowel disease. The pathogenesis of these disorders is unknown, but the variable relationships to the severity of colitis and the variable responses to a proctocolectomy suggest considerable heterogeneity. The present therapy for the various manifestations is reviewed in depth. In this respect it is important to note that colectomy should never be mandated by the extraintestinal complications of ulcerative colitis.

Arthritis↗

PubMed1998

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↗

PubMed2001

Heparin therapy for ulcerative colitis? Effects and mechanisms.

Despite intensive medical treatment with steroids and immunosuppressants, acute colitis is still associated with a colectomy rate of up to 15%. Following the observation that a patient with severe steroid-resistant colitis went into remission when treated with heparin for a deep vein thrombosis, there have been a number of reports on the use of heparin in acute ulcerative colitis. Although small and uncontrolled, these studies consistently demonstrate the beneficial effects of heparin, with surprisingly few side-effects in a disease characterized by mucosal haemorrhage. The mechanisms by which heparin may ameliorate ulcerative colitis remain unclear. A simple anticoagulant effect may be responsible, but similar effects are not seen with warfarin. As a result of their intense negative charge, the glycosaminoglycans that constitute heparin have diverse biological effects. These include potent anti-inflammatory actions, in vitro and in vivo, and the potentiation of the activity of the peptide growth factors necessary for mucosal regeneration and repair. This review summarizes the clinical reports on heparin treatment for ulcerative colitis and explores the mechanisms by which this novel form of treatment may exert its effects.

Adjuvants, Immunologic↗

PubMed2001

Expression of insulin-like growth factor binding proteins and collagen in experimental colitis in rats.

OBJECTIVES AND DESIGN: Crohn's disease is complicated by smooth muscle hyperplasia and stricture formation. Insulin-like growth factor (IGF)-1 and insulin-like growth factor binding proteins (IGFBPs) may be involved in stimulating intestinal smooth muscle growth and collagen synthesis. Therefore, we investigated the expression of IGFBPs, collagen and collagenase activity in rat colitis and the effects of IGF-1 on IGFBP and collagen expression in rat colonic smooth muscle cells. METHODS: Animals were sacrificed during a 4-week time course of 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced colitis. RNA from the animals' colons was blotted and hybridized with collagen-1 and IGFBP mRNA probes. Tissue proteins were screened for IGFBPs by Western ligand blotting. Collagenase activity was measured by zymography. Rat colonic smooth muscle cells in primary culture were incubated with IGF-1 then collagen-1, and IGFBP mRNAs and proteins were measured. RESULTS: In the rat tissue, IGFBP-3 mRNA and protein were increased 2 h after induction of colitis. IGFBP-4 mRNA was elevated after 2 h and IGFBP-4 protein after 4 h. IGFBP-5 mRNA was upregulated after 2 h with a peak at 12 h. IGFBP-5 protein was upregulated after 1 h and reached a peak at 3 days. Collagen-1 mRNA was increased after 5 days. Collagenase levels were decreased after 1 h and returned to normal by 28 days. In rat colonic smooth muscle cells, IGF-1 increased collagen-1 and IGFBP-5 expression. CONCLUSION: We demonstrated an upregulation of IGFBP and collagen expression and a downregulation of collagenase in rat colitis. In colonic smooth muscle cells, we found an upregulation of collagen-1 and IGFBP-5 following IGF-1 incubation. These results suggest an important role of IGF-1 in the collagen synthesis in colitis, mediated by IGFBPs.

Animals↗

PubMed2002

Octreotide in patients with active ulcerative colitis treated with high dose corticosteroids (OPUS 1).

BACKGROUND: In ulcerative colitis the intestinal somatostatin content is reduced. Somatostatin has several immune-inhibitory effects. In vitro it diminishes activity of intestinal lymphocytes and peripheral blood monocytes. Its long-acting analogue octreotide has beneficial effects on mucosal damage in acute experimental acetic acid colitis in rats. AIMS: To determine the potential benefits of octreotide as a treatment for patients with severe ulcerative colitis treated with high dose corticosteroids. PATIENTS: Forty-two patients with severe ulcerative colitis (more than 10 points on the Powell-Tuck scoring system and mucosal disease Heatly grade III or IV). METHODS: In a multi-centre, double blind, placebo-controlled trial all patients were treated with oral 5-ASA (1.6-2.4 g daily) and high dose corticosteroids (tapering off from 60 to 80 mg daily). They were randomly assigned to receive subcutaneous placebo (n = 22) or octreotide 500 microg (n = 20) thrice daily during 21 days. Clinical and endoscopic disease activity, histology and laboratory parameters were obtained during the study period. RESULTS: Clinical disease activity for both octreotide and placebo were not significantly different at baseline and after 21 days of treatment. Endoscopic disease activities (mean +/- SD) changed from 12.5 +/- 4.7 to 7.2 +/- 5.3 for octreotide, and from 11.5 +/- 5.0 to 5.0 +/- 3.4 for placebo (NS). Seven patients from both groups received additional treatment (colectomy (n = 6), cyclosporin (n = 1)). Adverse events occurred equally in both groups. CONCLUSIONS: Subcutaneous administration of octreotide 500 microg thrice daily is not of additional benefit as adjuvant therapy to high dose corticosteroids in severe ulcerative colitis.

Adult↗

PubMed2003

Segmental colitis: so what?

The existence of chronic mucosal inflammation, confined to sigmoid colons that bear diverticula, is termed 'segmental colitis'. This condition often mimicks inflammatory bowel disease at histological examination. The observed rectal sparing suggests a possible form of Crohn's disease, but no other similarities between segmental colitis and Crohn's colitis are detectable. Medical treatment for segmental colitis, empirically carried out with drugs such as sulfasalazine and mesalazine, is mostly successful and, when surgery is required, post-operative recurrences are infrequent. Although the existence of segmental colitis as a true clinical entity remains questionable, it appears unlikely that this condition represents an atypical form of inflammatory bowel disease.

Colitis↗

PubMed2003

Alternative approach to massive gastrointestinal bleeding in ulcerative colitis: highly selective transcatheter embolization.

Massive haemorrhage in ulcerative colitis mainly occurs as a result of exacerbated disease, usually acute or even fulminant colitis. Emergency proctocolectomy is currently advocated as the only reliable treatment of this patient group. However, this type of surgical intervention has a high rate of morbidity and mortality. Recently, several promising studies have been published that describe transcatheter embolization for the treatment of massive lower gastrointestinal bleeding in cases of bleeding colonic diverticular disease and angiodysplasia. Success rates of 48-88% have been reported. To avoid the high risk associated with emergency colectomy, this modern procedure was performed in an ulcerative colitis patient with intractable lower gastrointestinal bleeding. To our knowledge, this is the first patient with ulcerative colitis presenting with massive lower gastrointestinal blood loss to be successfully treated by highly selective transcatheter embolization. This interventional procedure is suggested as an alternative therapeutic approach to haematochezia in selected ulcerative colitis patients.

Colitis, Ulcerative↗

PubMed2004

Therapeutic effects of a new lymphocyte homing reagent FTY720 in interleukin-10 gene-deficient mice with colitis.

BACKGROUND: FTY720 is a novel reagent that possesses potent immunosuppressive activity. The immunosuppression induced by FTY720 is mediated by completely different mechanisms from those of conventional immunosuppressants, that is, by altering the tissue distribution of lymphocytes rather than inhibiting activation. In this study, we examined the efficacy of FTY720 in the treatment of chronic colitis in an interleukin-10 gene-deficient (IL-0-/-) mouse model. METHODS: FTY720 was administered orally for 4 weeks to IL-10-/- mice with clinical signs of colitis. The gross and histologic appearance of the colon and the numbers, phenotype, cytokine production, and apoptosis of lymphocytes were compared with those characteristics in a control group. RESULTS: Single-dose administration of FTY720 resulted in the sequestration of circulating lymphocytes within the secondary lymphoid tissues. Four-week administration resulted in a significant reduction of the CD4+ T lymphocytes subpopulation in the colonic lamina propria and IFN-gamma production of the colonic lymphocytes, accompanied by a significant decrease in the severity of colitis. CONCLUSIONS: Treatment of established colitis in IL-10-/- mice with FTY720 ameliorated the colitis, probably as a result of decreasing the number of lymphocytes in the colonic mucosa and an associated reduction in IFN-gamma production.

Animals↗

PubMed2004

Prospective evaluation of intestinal homing memory T cells in ulcerative colitis.

BACKGROUND: Intestinal homing (beta7+) memory T cells reflect the mucosal environment in which they were primed. We hypothesized that prospective assessment of cytokine production by intestinal homing (beta7+) memory T cells in ulcerative colitis patients followed from remission to early relapse may elucidate shifts in cytokine production relevant to the mucosal environment associated with the early phase of inflammation. METHODS: Twelve patients with frequently relapsing ulcerative colitis (> or = 2 relapses in the previous 12 months) were recruited in remission and followed prospectively until relapse. Antibody labeling of whole blood and flow cytometry were used to identify beta7+ cells and beta7- populations within CD3+CD45RA- leukocytes. Production of cytokines (IFN-gamma, TNF-alpha, IL-2, IL-10, TGF-beta, and IL-4) was determined by intracellular labeling. RESULTS: Early relapse of ulcerative colitis was associated with a shift of T cells from the naive to the memory T cell pool, and further the ratio of beta7+:beta7- memory T cells was significantly reduced at relapse (p < 0.01). A greater proportion of intestinal homing beta7+ memory T cells produced IL-4 (p < 0.02) and TNF-alpha (p < 0.05) at disease relapse compared with remission. Non-intestinal homing beta7- memory T cells also showed a tendency toward an increased production of TH1 and TH2 cytokines. CONCLUSIONS: The earliest phase of intestinal inflammation in ulcerative colitis patients is associated with an increase in both TH1 (TNF-alpha and TH2 (IL-4) cytokines by intestinal homing beta7+ memory T cells. These data support the principles of targeting lymphocyte trafficking as therapies in ulcerative colitis.

Adult↗