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PubMed2004

Urocortin 1 in colonic mucosa in patients with ulcerative colitis.

Ulcerative colitis (UC) is characterized by a long-standing chronic inflammation of the bowel with intermittent periods of exacerbation and remission. Its acute exacerbation appears to be related to various stresses. Urocortin 1 (Ucn1) may play important roles in integrated local responses to stress. We therefore examined local production of Ucn1 in patients with UC by immunohistochemistry and mRNA in situ hybridization. Ucn1 immunoreactivity was predominantly detected in lamina propria plasma cells and enterochromaffin cells. In UC patients without glucocorticoid treatment, Ucn1-positive cells and plasma cells increased in proportion to the severity of inflammation (P < 0.0001). Ucn1-positive cells significantly increased in UC patients with advanced inflammatory grades, compared with a control group (P < 0.0001) and nonspecific colitis group (P < 0.0001). In glucocorticoid-treated patients, Ucn1-positive cells were significantly lower in number, compared with the nonglucocorticoid-treated group. Ucn1 mRNA was expressed in lamina propria plasma cells, and both corticotropin-releasing factor(1) and corticotropin-releasing factor(2(a)) mRNAs were also partially coexpressed in these cells and macrophages. The present study showed that Ucn1-positive cells were correlated with the severity of inflammation in colonic mucosa with UC, and glucocorticoid treatment decreased these cells. Ucn1 therefore may act as a possible local immune-inflammatory mediator in UC.

Adult↗

PubMed2000

Ulcerative colitis.

Ulcerative colitis is a relatively common cause of altered bowel habit and rectal bleeding. Coordinated management of the investigation and care of patients with this condition is vital to optimize treatment. This article reviews current management options.

Adult↗

PubMed2006

Positions of selective leukocytapheresis in the medical therapy of ulcerative colitis.

Ulcerative colitis (UC) and Crohn's disease (CD) are the major forms of idiopathic inflammatory bowel disease (IBD). Both UC and CD are debilitating chronic disorders that afflict millions of individuals throughout the world with symptoms which impair function and quality of life. The etiology of IBD is inadequately understood and therefore, drug therapy has been empirical instead of being based on sound understanding of IBD pathogenesis. This is a major factor for poor drug efficacy and drug related side effects that often add to the disease complexity. The development of biologicals notably infliximab to intercept tumor necrosis factor (TNF)-alpha reflects some progress, albeit major concern about their side effects and lack of long-term safety and efficacy profiles. However, IBD seems to be perpetuated by inflammatory cytokines like TNF-alpha, interleukin (IL)-1beta, IL-6 and IL-8 for which activated peripheral granulocytes and monocytes/macrophages (GM) are major sources. Further, in IBD, peripheral GMs are elevated with activation behavior, increased survival time and are found in vast numbers within the inflamed intestinal mucosa; they are suspected to be major factors in the immunopathogenesis of IBD. Hence, peripheral blood GMs should be appropriate targets of therapy. The Adacolumn is a medical device developed for selective depletion of GM by receptor-mediated adsorption (GMA). Clinical data show GMA, in patients with steroid dependent or steroid refractory UC, is associated with up to 85% efficacy and tapering or discontinuation of steroids, while in steroid naive patients (the best responders), GMA spares patients from exposure to steroids. Likewise, GMA at appropriate intervals in patients at a high risk of clinical relapse suppresses relapse thus sparing the patients from the morbidity associated with IBD relapse. Further, GMA appears to reduce the number of patients being submitted to colectomy or exposure to unsafe immunosupressants. First UC episode, steroid naivety and short disease duration appear good predictors of response to GMA and based on the available data, GMA seems to have an excellent safety profile.

Colitis, Ulcerative↗

PubMed1998

Pharmacology and ulcerative colitis.

Ulcerative colitis can present in various stages, usually in the young adult. History, symptoms, and laboratory and bowel examination can lead to the diagnosis and proposed treatment. The response of the patient to the disease and drug therapy can vary. Ultimately, surgery may be necessary to prevent colon cancer. The aim is to achieve remission and provide the patient with as normal a life as possible.

Adult↗

PubMed1999

[Morphologic features of ulcerative colitis].

Ulcerative colitis(UC) is an ulcero inflammatory disorder of unknown etiology affecting only the mucosa and submucosa of colon and, with Crohn's disease, is included in the term idiopathic inflammatory bowel disease. The macroscopic and microscopic features vary according to the stage of the disease process, and an acute phase and a chronic or resolving phase can be recognized. The main differential diagnosis of UC is with colorectal Crohn's disease. The most feared long-term complication of UC is cancer. The progression of UC to carcinoma is closely associated with dysplasia arising in multiple sites. The dysplastic changes should be distinguished from the epithelial changes resulting from regenerative atypia, and the evaluation of these changes is difficult. P53 immunohistochemical staining is helpful in confirming the presence of dysplasia. Molecular events in colorectal carcinogenesis of UC may be somewhat different from those of so-called adenoma-carcinoma sequence.

Colitis, Ulcerative↗

PubMed1999

[Arthritic manifestations in ulcerative colitis].

Ulcerative colitis (UC) is commonly associated with peripheral joint disease which correlates with the activity and extent of the inflammatory bowel disorder. They are generally divided into three clinical categories; peripheral arthritis, spondylitis, and sacroiliitis. The arthritis is usually pauciarticular, generally asymmetric, transient, and nondestructive. However, the peripheral arthritis becomes chronic and destructive in some cases. Rheumatoid arthritis has been reported to be seldom associated with UC. Inflammatory joint disease is considered an enteropathic arthritis if the gastrointestinal tract is directly involved in the pathogenesis. The occurrence of rheumatologic manifestations in UC is reviewed in this paper.

Arthritis↗

PubMed1999

[Clinical features and management of the elderly patients with ulcerative colitis].

Ulcerative colitis(UC) is commonly observed in young generation, but a considerable number of patients(1.7-4.6%) distribute over 65 years old. The clinical features of the elderly UC patients are not so severe, and most of them could maintain clinical remission after treatment. These are the most characteristic features of the elderly UC patients. Although the elderly UC patients are treated with similar therapeutic strategy for younger UC patients, we must pay an attention to several special points, e.g. differences in drug efficacy and complication with other diseases. Especially it must be emphasized that the risk of colon cancer development is much higher in the elderly UC patients, and strong efforts should be paid to the surveillance for colon cancer in these patients.

Age of Onset↗

PubMedDate not supplied

Current treatment of ulcerative colitis.

Ulcerative colitis is a chronic relapsing disease which may become manifest either early or late in life. This article examines current drug treatment strategies and considers possible therapeutic options for the future.

Adrenal Cortex Hormones↗

PubMed2005

[The concept, criteria for diagnosis, and disease classification of ulcerative colitis].

Ulcerative colitis (UC) is an idiopathic, non-specific inflammatory disorder involving primarily the mucosa and submucosa of the colon, especially the rectum. It usually produces a bloody diarrhea and various degrees of systemic involvement. These definitions of idiopathic proctocolitis were established by Council for International Organization of Medical Science (CIOMS) in 1973. In Japan, the first criteria for diagnosis of UC were established by the Research Committee of UC (the Japanese Ministry of Health and Welfare) in 1974, based on the definitions by CIOMS. Since then, some minor revisions have been made. The newest criteria for diagnosis of UC were published in 1998. The diagnosis of UC is made on the basis of a combination of clinical, endoscopic, radiologic, and histologic findings.

Colitis, Ulcerative↗

PubMed2005

[Etiopathogenesis and aggravating factors in ulcerative colitis].

Ulcerative colitis (UC) is a chronic inflammatory disease limited to the colon. Although the pathogenesis of inflammatory bowel disease (IBD) remains unclear, several studies have suggested that the onset and development of IBD require the interaction between genetic susceptibility, stimulation by luminal bacterial antigens and adjuvants, and episodic environmental triggers which break the mucosal barrier. There are many reports that experimental enterocolitis in animals does not occur in a sterile (germ free) environment and is prevented by antibiotics therapy. Moreover, patients with UC exhibit pathological immune responses to many commensal enteric bacterial species. Recent data showed that certain probiotic species decrease relapse of UC. These findings suggest that the most possible cause of UC is associated with chronic intestinal inflammation which is induced and perpetuated by non-pathogenic bacteria in genetically susceptible hosts.

Animals↗

PubMed2005

[Immunosuppressants for therapy of patients with ulcerative colitis].

Ulcerative colitis (UC) has been known as inflammatory bowel disease. Progress in UC management strategies has led to optimized approaches for achieving the two primary clinical goals of therapy: induction and maintenance of remission. We here review about immunosuppressants in management of UC; Cyclosporine A (CsA) has been used for the induction therapy in steroid resistant refractory UC. Although it has been reported that CsA has high response rate in severe UC, long-term efficacy (maintenance of remission) has not been proven. To improve maintenance therapy, immunosuppressant has been re-considered in management of UC. In recent years, it has been reported that efficacy of 6-mercaptopurine/azathioprine in maintenance of remission of UC is superior to 5-aminosalicylate (5-ASA). Pharmacological studies have indicated thiopurine methyltransferase (TPMT) activity is essential for maintenance of blood concentration of 6-thioguanine nucleotide (6-TG).

Azathioprine↗

PubMed2006

Cellular and molecular immunopathogenesis of ulcerative colitis.

Ulcerative colitis (UC) is an inflammatory disease of the rectal and colonic mucosa and seems to result from a complex series of interactions between susceptibility genes, the environment and the immune system. Various components of the mucosal immune system are implicated in the immunopathogenesis of UC. Evidence from animal models also suggests that an altered immune response to the commensal microflora of the host plays a central role in the development of UC. So in this review, we elucidate the cells and molecules which are implicated in the immunopathogenesis of the disease from four aspects: antigens in the intestine, dendritic cells, toll like receptors and NF-kappaB in the UC.

Animals↗

PubMed2006

A two-stage decision analysis to assess the cost of 5-aminosalicylic acid failure and the economics of balsalazide versus mesalamine in the treatment of ulcerative colitis.

Ulcerative colitis (UC) is a costly disease, especially if not properly treated. Epidemiologic studies have shown that many patients progress in one year from initial treatment with prednisone to expensive colonectomy surgery if the UC is not managed with drug therapy. A two-stage decision analysis was conducted to (1) estimate the cost of a 5-aminosalicylic acid (5-ASA) treatment failure using the treatment guidelines recommended by the American College of Gastroenterology and (2) incorporate the cost of a 5-ASA treatment failure to determine which oral 5-ASA agent results in cost minimization and cost effectiveness. The analysis was conducted from the payer perspective, incorporating results from clinical trials directly comparing oral balsalazide capsules and a specific formulation of oral mesalamine. Health care costs related to UC for an oral 5-ASA failure is greater than dollar 11,500 on average in the first six months after therapy. Patients treated with balsalazide capsules had 16% lower total direct health care costs, 32% better outcomes (days without symptoms or steroids), and 37% greater cost effectiveness compared with patients treated with a specific formulation of oral mesalamine. Coordinated efforts should be taken to avoid the cost and morbidity associated with 5-ASA treatment failures.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1989

Surgical therapy in ulcerative colitis.

Ulcerative colitis is cured if the colon and rectum are removed. The total proctocolectomy provides the cure, but the ileostomy is not well accepted by patients. Thus, alternatives that provide continence but have an increased morbidity have been introduced. The continent ileostomy (Koch pouch) has a valve created in an ileal pouch which provides continence. Intubation with a catheter is necessary and a flat ostomy is present. A colectomy with ileoproctostomy can be used to salvage the sphincter. Unfortunately, the diseased rectum is spared with its potential for progressive symptoms and cancer. The newest technique is also the most morbid. This procedure requires total colectomy, stripping of the rectal mucosa, formation of an ileal pouch, anastomosis of the pouch to the anus, and placement of a diverting ileostomy to allow complete healing without passage of stool. The failure rate is five to ten per cent, but most young people opt to save the sphincter and preserve their body image.

Colectomy↗

PubMed1995

[Surgical treatment of ulcerous colitis].

Ulcerative colitis, being a typical medical disease, is encountered by the surgeon only in the stage of toxic megacolon or in case of sever complications during conservative treatment such as perforation, haemorrhage or obstruction. The authors operated six young women where they performed as the only choice total proctocolectomy with formation of an ileal reservoir which was sutured to the rectum stripped of the mucosa. Despite the serious condition at the time of operation, the patients survive the operation, although the percentage of postoperative complications is high, with the exception of one patient who died on the 126th day after operation. The remainder survive in a fair condition with complete and continence.

Adolescent↗

PubMed1994

Ulcerative appendicitis in universal and nonuniversal ulcerative colitis.

Ulcerative appendicitis (UA), the appendiceal counterpart of ulcerative colitis (UC), is frequently present in colectomy specimens from patients with universal UC and is regarded as part of the continuous inflammatory process that is a hallmark of this disease. It has been reported, although not universally accepted, that UA may also occur in UC that spares the proximal colon, constituting a skip lesion. Colectomies, which included appendices, from 160 consecutive adult and pediatric patients with UC were reviewed histologically and separated into two groups, universal and nonuniversal UC, on the basis of a stringent histopathological definition of normal mucosa. Forty-five cases with obliterated appendiceal lumens were excluded. UA was present in 82 of the 94 cases of universal UC (87%), including 75 of the 83 adult cases (90%) and 7 of the 11 pediatric cases (64%). UA was present in 18 of the 21 cases of nonuniversal UC (86%), all of which were adults, representing skip lesions. UA was found in 12 of the 14 cases in which colitis commenced distal to the hepatic flexure, including 2 of the 3 cases of left-sided colitis and 2 of the 2 cases of proctosigmoiditis. Among patients whose clinical indication for colectomy was the presence of dysplasia or carcinoma and who had patent appendices, UA was present in 6 of the 9 cases with universal UC (68%) and in each of the 3 cases with nonuniversal UC (100%). We conclude that in colectomy specimens discontinuous appendiceal involvement in nonuniversal UC is as prevalent as continuous involvement in universal UC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1996

Phage display cloning and characterization of an immunogenetic marker (perinuclear anti-neutrophil cytoplasmic antibody) in ulcerative colitis.

Ulcerative colitis (UC) is genetically associated with a marker serum Ab (pANCA), identified by its reactivity with a neutrophil Ag. This study utilized phage display technology to clone and characterize pANCA, which has resisted conventional isolation strategies. Since spontaneous pANCA-secreting B cells are detectable in UC lamina propria lymphocytes, this cell source was used to construct a complete IgG1-kappa Ig library. Selection of phage by panning with fixed neutrophils yielded a 195-fold enrichment after five cycles of panning. BstN1 fingerprinting of the enriched library revealed two predominant clones, and DNA sequencing demonstrated highly homologous heavy and light chain variable region segments. Clones were reengineered to express soluble Fab, and neutrophil binding was verified by ELISA. Detailed studies with the two recombinant Fabs, NANUC-1 and -2, validated their identity with serum pANCAs by the criteria of immunofluorescence, confocal microscopy, and DNase I sensitivity. NANUC-1 and -2, like serum UC-pANCA, lack reactivity with previously characterized ANCA-reactive neutrophil proteins and thus detect a novel Ag(s). This study demonstrates the feasibility of selecting phage display Ab libraries on uncharacterized biologic substrates to isolate marker Abs of pathogenic importance.

Amino Acid Sequence↗

PubMed1996

Immune thrombocytopenic purpura in three patients with preexisting ulcerative colitis.

Ulcerative colitis (UC) is associated with extraintestinal diseases in numerous target tissues. Associated immune-mediated hematological diseases, however, are rarely described. We report three Caucasian adult patients with UC and immune thrombocytopenic purpura (ITP). Platelet-associated antibodies (IgG) were positive in two patients, and bone marrow examinations in two patients revealed normal to increased megakaryocyte numbers. ITP was treated with corticosteroids in all patients. Two patients eventually received intravenous immune gamma-globulin, and one patient required surgical splenectomy. Of particular interest, UC preceded the onset of ITP in all patients (by from 1 to 19 yr). This suggests that ITP in these patients is causally associated with UC, possibly secondary to immunostimulation from lumenal antigens and altered immunoregulation.

Adult↗