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PubMed2001

Epithelial proliferation and ras p21 oncoprotein expression in rectal mucosa of patients with ulcerative colitis.

In ulcerative colitis (UC), epithelial proliferation plays a role in crypt repair and neoplastic evolution. Proliferative status is predominantly connoted in active disease, but not defined in remission. Histologically, remission is characterized by normalization of the picture or development of atrophy. Mutation of the ras oncogene is involved in intestinal carcinogenesis. Aim of this work was to assess the proliferative pattern of rectal epithelium in UC during disease activity and in remission and correlate it with ras oncoprotein p21. The study was performed retrospectively in rectal biopsies from four groups each of 10 patients: active ulcerative colitis (AUC), remission with a normal histology (RUC), remission with rectal atrophy (ARUC), and irritable bowel syndrome (C, control group). In all, immunohistostain was employed to evaluate the proliferation cell nuclear antigen labeling index (PCNA LI) and ras p21. Statistical analysis was performed by ANOVA and Student-Neumann-Keuls tests. PCNA LI was significantly higher in AUC and ARUC than in RUC and C. Positive cells were predominant in the lower zone of crypts in RUC and C, while a significant expression of PCNA was also observed in the upper areas in AUC and ARUC. Oncoprotein p21 was expressed on the apical surface of the epithelium in 3/10 AUC patients, in all 10 ARUC patients and in none of RUC and C. The persistently increased epithelial proliferation associated with ras p21 expression in ARUC may be due to the action of an abnormal, mutated ras gene that could play a role in UC-related tumorigenesis.

Adult↗
PubMedDate not supplied

[Changes in the number of neuroprotective transmitter containing mucosal nerve fibres in children with ulcerative colitis].

INTRODUCTION: Ulcerative colitis and Crohn's disease are two main disease entities that belong to the group of inflammatory bowel diseases (IBD). Chronic inflammatory process concerning intestinal mucosal membrane causes structural and functional changes of intestinal nervous system. This phenomenon is called the plasticity of the nervous system and is due to the ability of nerve cells to adapt to changing environmental conditions. The resulting alterations of intestinal neurons' chemical code are augmentation, inhibition or initiation of the neurotransmitters' synthesis (synthesis "de novo"). The role of neuroprotective transmitters - galanine (GAL), vasoactive intestinal peptide (VIP) and pituitary adenosine cyclase activating peptide (PACAP) seems to be important in the pathogenesis of inflammatory bowel diseases. They are responsible for the regulation of intestinal contraction and modification of ions' transport in the intestinal epithelium. They also diminuate the inflammation by modulation of the proinflammatory chemokines and cytokines production. THE AIM: of the study was to analyse the changes in the nerve fibres' containing GAL, VIP and/or PACAP, density in the mucosal membrane of children with ulcerative colitis (UC) with different Clinical activity index. MATERIAL AND METHODS: the study included 33 children hospitalised due to UC with different activity and 9 children in the control group, after exclusion of IBD. All the studied patients underwent colonoscopic examination with colon mucosa biopsies. Histology and immunochemistry of mucosal samples were analysed. Those studies helped to assess the changes in the number of nerve fibres containing analysed transmitter substances in the mucosal membrane of the colon. RESULTS: the results showed a statistically significant diminuation of nerve fibres containing analysed neurotransmitters number in colon mucosa samples of children with UC. There were no statistically significant changes in number of nerve fibres dependent on the clinical activity index of UC. CONCLUSIONS: the process of degradation present in UC is accompanied by the important diminuation on neurotransmitter containing fibres number. However, their density is not dependent of the clinical activity of the disease.

Adolescent↗
PubMed2003

[Ulcerative colitis and cytomegalovirus infection].

Colitis ulcerous and citomegalovirus infection association have been reported in medical literature in sometimes, althougth this prevalence have lately increased. We report a case record of this association and do a review of this subject. It is not clear what factors are involved in this association, being necessary hore studies to know them.

Aged↗
PubMed2006

[Risk factors for ulcerative colitis associated colorectal cancers in a Hungarian cohort of ulcerative colitis patients].

BACKGROUND: There is an increased risk of colorectal cancer (CRC) in ulcerative colitis (UC). The prevalence of UC associated CRC is different in various geographical regions. The risk depends primarily on the duration and extent of disease. AIM: The aim of the study was to identify risk factors for and epidemiology of CRC in UC patients in Veszprem province. PATIENTS AND METHODS: From our thirty-year IBD database we retrospectively studied the relevant epidemiological and clinical data of all UC patients in Veszprem province. The data of 723 UC patients (m/f: 380/343) were evaluated. The rate of familial disease was 5.2%, the rate of non-CRC related colectomies was 3.7% in our UC patients. RESULTS: CRC was diagnosed in 13 patients (m/f: 6/7, 13/8564 person year duration) during follow-up. The onset of UC in the 13 patients with UC-CRC was 34.5 (13-61) years, 4.1 years younger compared to UC patients without CRC. Mean age of UC-CRC patients at diagnosis of CRC was 50.9 (27-70) years (duration of UC: 16.5 +/- 8.2 years), almost 15 years younger than the average in sporadic CRC population in Hungary. Eight patients are still alive (survival: 67.9 (10-163) months), four patients died because of CRC (survival: 8.0 months), one died due to unrelated cause after 10 years of the diagnosis of CRC. Longer disease duration, chronic continuous disease, more extensive colitis, the presence of iron deficiency or chronic anaemia, primary sclerosing cholangitis (PSC) and dysplasia in the biopsy were identified as risk factors for developing CRC. In a logistic regression model longer disease duration, extensive colitis, PSC and dysplasia were still associated with increased risk. The cumulative risk for developing CRC after a disease duration of 10 years was 0.6% (95% CI: 0.2-1.0%), at 20 years 5.4 % (95% CI: 3.7-7.1%) and at 32 years 12.6% (95% CI: 7.0-18.2%). CRC diagnosed at surveillance colonoscopy was associated with longer survival (p = 0.04). CONCLUSION: The cumulative risk of CRC was high in our UC patients, however it was lower compared to that reported in Western European and North American studies. CRC developed approximately fifteen years earlier compared to the sporadic CRC cases. Long disease duration, extensive colitis, the presence of iron deficiency or chronic anaemia, dysplasia and primary sclerosing cholangitis (PSC) seem to be important risk factor for developing CRC in UC patients.

Adult↗
PubMed2002

Polymorphisms of the IL-1beta and IL-1beta-inducible genes in ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic disorder of undetermined etiology, but a genetic predisposition to UC is well recognized. Among cytokines induced in UC, interleukin 1 (IL-1) appears to have a central role because of its immunological upregulatory and proinflammatory activities. The aim of this study was to assess whether UC is associated with polymorphisms of the IL-1beta gene and three additional genes inducible with IL-1beta in Japanese subjects. METHODS: A total of 96 patients with UC and 106 ethnically matched controls were genotyped at polymorphic sites in IL-1beta, matrix metalloproteinase 1 (MMP-1), matrix metalloproteinase 3 (MMP-3), and inducible nitric oxide synthase (iNOS) genes, using polymerase chain reaction (PCR)-based methods. RESULTS: There was no significant difference in genotype distributions of IL-1beta, MMP-1, MMP-3, and iNOS genes between controls and UC patients in a Japanese population. Also, no significant association of those polymorphisms with various clinical parameters of the patients was found. However, concerning association of age at onset with clinical factors in UC, the frequency of pancolitis was significantly higher in UC patients with age at onset being less than 30 years than in those more than 30 years of age (P = 0.049). CONCLUSIONS: No association of the IL-1beta and three IL-1beta-inducible gene polymorphisms with UC was observed in a Japanese population.

Adolescent↗
PubMed2003

Patterns of disease and surgical treatment among United States veterans more than 50 years of age with ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a clinical entity that predominantly affects young adults yet large series of middle age or elderly patients with UC are infrequently reported. The aim of this study is to identify patterns of disease, indications for operation, surgical treatment, and outcome of patients more than 50 years of age who required surgery for UC in Department of Veterans Affairs (DVA) Medical Centers. METHODS: A population-based study on all patients in 159 hospitals of the DVA from 1997 to 2001 was carried out. Data were compiled from several national computerized VA data sets. Supplementary information including demographic information, discharge summaries, operative reports and pathology reports were obtained from local medical records. Patient variables were entered into a computerized database and analyzed using the Pearson chi-square and Fisher's exact tests. Statistical significance is designated as P < 0.05. RESULTS: One hundred fifty-eight patients were evaluable. The mean age was 59 years (range 51-81); 99% were male. The mean duration of UC was 23 years (range 2 to 50). One hundred of the 158 patients had proctocolitis; 58 had either left-sided colitis or proctosigmoiditis. The mean dose of prednisone prior to surgery was 20 mg; the mean duration of steroid use was 8 years. The indications for elective surgery were intractability (59%), mass or stricture (27%), and dysplasia (14%). Twenty of the 158 patients (12%) were operated on emergently for either toxic colitis, perforation, or hemorrhage. One hundred three of the 158 underwent proctocolectomy and permanent ileostomy, 55 underwent a restorative proctocolectomy, and underwent a segmental colectomy. Twenty of the 158 patients were found to have dysplasia in their colectomy specimens; an additional 10 (7%) were found to have invasive cancer. Surgical morbidity was 22%. Overall mortality was 4% (7 of 158); all but 1 death occurred after emergent surgery. Mean hospitalization was 36 days (range 2 to 297). CONCLUSIONS: Restorative proctocolectomy was performed in 36% of veterans more than 50 years of age requiring surgery for UC. The majority required surgery for intractable symptoms. Dysplasia and invasive cancer was found in 18% of patients. Mortality after surgery for acute surgical emergencies remains high.

Case-Control Studies↗
PubMed2004

Relationship between fecal calprotectin, intestinal inflammation, and peripheral blood neutrophils in patients with active ulcerative colitis.

Active ulcerative colitis (UC) is associated with elevated granulocytes and monocytes/macrophages (GM) which show activation behavior and increased survival time. Further, fecal calprotectin (a stable neutrophil protein) level parallels intestinal inflammation and can predict UC relapse. Since GM are major sources of inflammatory cytokines and chemokines, they are suspected to have roles in the initiation and perpetuation of UC. Our objective was to investigated relationships between peripheral blood (PB) neutrophils, calprotectin, and UC disease activity. Full PB and calprotectin were determined in 69 healthy controls and 31 patients with UC, then 7 randomly selected patients received GM adsorptive apheresis (GMA) with Adacolumn, 10 sessions of 60-min duration each. Patients with UC had higher neutrophil counts (P < 0.001), but lower lymphocyte counts (P < 0.001) compared with controls. Further, fecal calprotectin levels showed a correlation with UC clinical activity index (CAI; P < 0.001) and mucosal inflammation (P < 0.001). Following GMA, there were falls in neutrophils (P < 0.02), CAI (P < 0.02) and calprotectin (P < 0.02). In conclusion, GM appear to contribute to intestinal inflammation and UC activity and reduction of these cells by GMA should benefit patients with active UC. Further, the correlations among calprotectin, UC activities, and PB neutrophils should serve as the basis for preemptive actions to control this disease.

Adolescent↗
PubMed1997

Review article: the management of severe ulcerative colitis.

Severe ulcerative colitis is a potentially life-threatening condition but the mortality has fallen dramatically over the past 30-40 years. It is now less than 2%, including surgical mortality, and should only be seen in patients with significant co-existing disease. Early recognition of the severity of the colitis, intensive medical therapy, close liaison between physician and surgeon, and prompt surgery when necessary have all contributed to this improved outcome. Despite the use of high-dose intravenous corticosteroids, 20-30% of patients will make a poor response and will require urgent surgery. The use of intravenous cyclosporin has proved effective at reducing the immediate surgical rate in this group of unresponsive patients and appears safe. Whether cyclosporin reduces the need for surgery in the longer term is much less certain. Clinical, radiological, endoscopic and laboratory parameters can now be used to predict the course of a severe attack. These help in the timing of urgent surgery and are potentially helpful in determining when to begin other therapies such as cyclosporin.

Aminosalicylic Acids↗
PubMed2002

Mast cells and inflammatory mediators in chronic ulcerative colitis.

Chronic ulcerative colitis (CUC) is an inflammatory destructive disease of the large intestine characterized by motility and secretion disorders. In the past decade, attention has been paid to the role of neuronal structures and mast cells in regulating inflammatory and immune responses in inflammatory bowel disease (IBD). The present study was performed to demonstrate neuronal fibres (NF) and cells containing substance P (SP), tryptase and serotonin (SER) in the colonic wall of patients with CUC in remission. Biopsy specimens of 6 patients with CUC were investigated with immunocytochemical methods. Normal colon tissue obtained from 6 patients with rectal carcinoma was used as a control. An increased number of SP- and SER-positive NF was found in all the layers of the intestinal wall. The number of SER-containing endocrine cells in the mucosal glands was also increased per crypt. Tryptase-, SP- and SER-immunopositive mast cells were found in higher amounts than in control specimens in close apposition to the basal lamina of the glands among the epithelial cells and in other layers of the gut wall. Two types of mast cells were found: mast cells containing both tryptase and SP, and mast cells containing tryptase only. It is concluded that interactions between neuronal elements and mast cells play a significant role in the progress and maintenance of inflammatory processes in CUC.

Cell Count↗
PubMed2002

Clinical and colonoscopic investigation of skipped periappendiceal lesions in ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is typically a continuous and diffuse inflammation extending proximally from the rectum. However, skipped lesion in the appendiceal region has been reported recently. Although appendectomy has been shown to reduce the risk of UC, the clinical significance of skipped periappendiceal lesion remains unclear. The present study examined the relationship between the continuous distal lesion of UC and the skipped periappendiceal lesion by observing colonoscopic changes in both lesions. METHODS: Among 279 patients with UC who underwent total colonoscopy from January 1994 to December 2000, 54 patients (19.4%) had skipped periappendiceal lesions. Serial colonoscopic examinations were performed in 35 of the 54 patients to determine the activities in the distal UC lesion and skipped periappendiceal lesion during the course of disease. RESULTS: Patients with skipped periappendiceal lesions were younger and had a longer history of UC than those without them, but no differences in sex ratio and treatment modality were observed between the two groups. In 28 of 35 patients (80%), the activity in the distal lesion correlated well with that in the skipped periappendiceal lesion. Both lesions were improved in 17 patients, unchanged in 5 patients and worsened in 6 patients. Linear regression analysis showed a significant correlation between the changes in colonoscopic activity index in the two lesions. CONCLUSION: A close association is found between disease activity in the skipped periappendiceal lesion and that in the distal lesion of UC.

Adult↗
PubMed2003

Effect of smoking and transdermal nicotine on colonic nicotinic acetylcholine receptors in ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a disease largely of non-smokers, in which nicotine is of therapeutic value. The mode of action is unknown, but may involve nicotinic acetylcholine receptors (nAChRs) in the bowel wall. AIM: To investigate the presence of nAChRs in rectal mucosa, and the effect of smoking and nicotine on their expression. DESIGN: Prospective case-control study. METHODS: In situ hybridization (ISH) and immunocytochemistry (ICC) were used to show alpha3 nAChRs in colonic mucosa. Rectal mucosa was examined from controls (n=55) and patients with inactive UC (n=62), both smokers and non-smokers, by ICC, using two antibodies to show the density and distribution of receptors in the mucosa. Non-smokers with UC (n=43) were given transdermal nicotine or placebo patches for 6 months, and rectal biopsies, taken before and after treatment, were examined by ICC to show nAChRs. RESULTS: In normal colon, ISH and ICC showed alpha3 subunit in a wide variety of cells, including mucosal epithelium. In rectal biopsies, neither smoking nor nicotine influenced the expression of alpha3 immunoreactivity in epithelium, either in controls or UC. However, controls had a significantly greater density of immunodetectable mucosal epithelium alpha3 subunit, compared with UC patients. DISCUSSION: The presence of nAChRs in colonic epithelium may be pertinent to the beneficial effect of nicotine in UC, but since neither smoking nor nicotine treatment is associated with any change in the expression of epithelial alpha3 nAChRs, the effect may be due to functional changes in the receptor. The decreased number of alpha3 nAChRs in UC compared with controls may be related to an increased cell turnover in UC.

Administration, Cutaneous↗
PubMed2001

Tc-99m HMPAO white blood cell scintigraphy in the assessment of the extent and severity of an acute exacerbation of ulcerative colitis.

PURPOSE: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with frequent exacerbations, including the risk for toxic megacolon and severe complications. In very active disease, colonoscopy should not be performed to assess the severity and the extent of the disease. The aim of the current study was to determine whether Tc-99m HMPAO-labeled white blood cell (WBC) scintigraphy can be used as an alternative to colonoscopy to determine the extent and the severity of the disease in critically ill patients. METHODS: Twenty consecutive patients (7 women, 13 men; age 38.1 +/- 13.1 years) who had a severe attack of UC underwent scintigraphy on the day of admission. Leukocytes were labeled with 200 MBq (5.35 mCi) Tc-99m HMPAO. Planar anterior and posterior imaging of the abdomen was performed 45 and 120 minutes after WBC reinjection. The tracer uptake in the different colon segments was scored visually compared with bone marrow uptake. A symptom score was made and C-reactive protein was measured as a serologic marker of inflammation. Rectosigmoidoscopy with biopsy was performed within 24 hours of scintigraphy. Scintigraphic, endoscopic, and histologic results were compared for disease activity. RESULTS: The mean symptom score was 12.7 (+/-0.7) on a scale of 21, and mean the C-reactive protein level was 6.8 (+/-1.2) mg/l. No significant difference was found between the scintigraphic score of the rectum and the endoscopic or the histologic score. The best correlation was found with the latter (r = 0.66, P < 0.01). Based on the results of scintigraphy, disease involved the left side of the colon up to the splenic flexure in 10 patients. The other patients had pancolitis. CONCLUSIONS: Disease severity can be determined adequately by planar WBC scintigraphy in patients with severe attacks of UC. Because the presence and severity of disease correlates well with endoscopic and histologic findings, WBC scintigraphy can assess disease extent without the need for colonoscopy. This decreases the number and severity of complications that can occur in already critically ill patients.

Acute Disease↗
PubMed2004

Endoscopic rectal sparing in children with untreated ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) typically is associated with a confluent proctitis, whereas rectal sparing may be seen in large bowel Crohn disease (CD). A few studies have reported rectal sparing in UC and suggested that this might indicate a more severe form of the disease. This study aimed to determine the prevalence and prognostic significance of rectal sparing in children with newly diagnosed, untreated UC. METHODS: The records of all children with untreated UC presenting to a regional pediatric gastroenterology service between January 1996 and December 2001 were retrospectively reviewed. Patients were divided into two groups according to the endoscopic appearance of the rectum: Group 1 (proctitis) and Group 2 (rectal sparing). Clinical features, intractability index (duration of active disease as a proportion of length of follow-up), response to treatment, relapse index (number of recurrences per year), and the need for surgery were compared. RESULTS: Thirty children with untreated UC were identified. Seven (23%) had rectal sparing at initial endoscopy, but disease distribution was otherwise similar in both groups. Presenting symptoms were similar in those with and without rectal sparing. In Group 1, 20 (87%) children achieved remission with initial medical treatment, compared with 3 (43%) in Group 2 (P < 0.05). The intractability index was higher in children with rectal sparing, but the difference was not statistically significant (P = 0.22). During a median follow-up period of 2 years, one (4%) child in Group 1 and two (29%) children in Group 2 experienced primary sclerosing cholangitis, and two (29%) children with rectal sparing required colectomy, compared with none in Group 1. CONCLUSIONS: Endoscopic rectal sparing was seen in 23% of children with newly diagnosed, untreated UC, but this feature did not correlate with presenting symptoms. However, the presence of rectal sparing may indicate more aggressive disease that is less responsive to medical treatment.

Adolescent↗
PubMed1997

From basic science to future medical options for treatment of ulcerative colitis.

Both ulcerative colitis (UC) and Crohn's disease are considered the result of an unrestrained inflammatory reaction, but an explanation for the aetiopathogenesis has still not emerged. Until the predisposing and trigger factors have been clearly defined, therapeutic and preventive strategies for these disorders must, therefore, rely on interrupting or inhibiting the immunopathogenic mechanisms involved. Current therapies, such as glucocorticoids and 5-aminosalicylic acid, inhibit raised concentrations of interdependent, soluble mediators of inflammation, which may amplify one another or have parallel effects. Future medical options for treatment of UC aim at removing perpetuating antigens, blocking entry of inflammatory cells by manipulating adhesion molecules, targeting soluble mediators of inflammation by blocking proinflammatory molecules or by preserving endogenous suppressive molecules, or correcting genetic defects. It remains, however, to be determined whether targeting multi-inflammatory actions or a single key pivotal process is the better therapeutic strategy and whether subgroups of UC with different clinical courses will require different treatment approaches.

Antibody Formation↗
PubMed2005

CTLA-4 gene polymorphisms in Chinese patients with ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is characterized by chronic inflammation of the colon and rectum as a result of an exaggerated T-cell response. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a T cell-restricted surface molecule induced with TCR or CD28 activation. There is evidence for genetic involvement of CTLA-4 in several autoimmune diseases, with the focus on the possible role of genetic variation of the CTLA-4 locus. The aim of this study was to investigate CTLA-4 gene polymorphisms in patients with UC in a Chinese population with Han nationality. METHODS: The C-318T polymorphism in the promoter region and A+49G polymorphism in exon 1 of the CTLA-4 gene were studied by a polymerase chain reaction-sequence-specific primer method. We studied 82 unrelated patients with UC and 204 healthy controls in a Chinese population with Han nationality. RESULTS: The frequency of the haplotype 2,3 (-318C+49G/-318T+49A) was 26% in patients with UC and 41% in healthy controls (Fisher exact test P = 0.0147, odds ratio = 0.4918, 95% confidence interval: 0.2784 - 0.8688), but this significance disappeared when Bonferoni correction was applied. No other significant differences in the distribution of allele and genotype frequencies were observed between C-318T and A+49G gene polymorphisms and UC in the Chinese Han population. CONCLUSION: The C-318T and A+49G polymorphisms of the CTLA-4 gene were not associated with UC in Chinese Han patients.

Adolescent↗
PubMed2006

Chromosomal and microsatellite instability of adenocarcinomas and dysplastic lesions (DALM) in ulcerative colitis.

Longstanding ulcerative colitis (UC) is associated with a high risk of developing UC-related colonic adenocarcinoma (UCC). These carcinomas originate from nonadenomatous dysplastic regions referred to as dysplasia associated lesion or mass (DALM). We evaluated chromosomal and microsatellite instability (MSI) in 21 DALM/UCCs. Chromosomal instability was determined by high-resolution array comparative genomic hybridization with a 3500-element BAC-PAC array. MSI was assessed with markers BAT25 and BAT26 and by immunohistochemical analysis of mismatch repair genes. Comparative genomic hybridization revealed frequent losses of array clones (>20% of tumors) at chromosome arms 4p, 5q, and 18q, frequent gains of array clones (>20% of tumors) were found at 1q, 5p, 6p, 7p, 7q, 8p, 8q, 11p, 11q, 12q, 14q, 17q, 19q, 20p, and 20q. The pattern of alterations is dominated by gains on 5p and 20q with loss of 4p, all of which were already present in a patient with carcinoma in situ. Immunohistochemical analysis of mismatch repair genes MLH1, PMS2, MSH2, and MSH6 showed negative immunostaining in 1 neoplasm (5%). MSI of BAT25 and BAT26 was seen in 3 tumors (14%) including the neoplasm with aberrant immunostaining. In conclusion, we constructed a genomic profile of DALM/UCC including several novel genetic alterations. Further, we found a low percentage of MSI. Thus, DALM/UCCs display profound chromosomal instability, but this is not associated with concurrent MSI.

Adenocarcinoma↗