The first option for the treatment of UC is both: salicylates or corticoids. Recently, in late November of 2006, the Brazilian Ministry of Health has approved infliximab (Remicade c, Mantecorp, Brazil) to treat ulcerative colitis. We report the use of infliximab as a first option for the treatment of two patients with severe ulcerative colitis. Case report: Patient 1: AZF, 52 years-old, female, was first diagnosed with UC after history and clinical examination; colonoscopy showed pancolitis with positive biopsy (crypt microabscess). Her Mayo score was 10 (range: 0 to 12/asymptomatic to severe colitis). She received intra venous infusion of infliximab at a dose of 5mg/Kg of body weigh at week 0, 2, 6 and 14. Then, patient was given mesalazine 4.5 g/day for maintenance therapy. Clinical response was defined as a decreased from baseline in the total Mayo score of at least 3 points. At present, patient is asymptomatic with Mayo score of 3 one moth after the last dose of infliximab. Patient 2: MLA, 45 years-old, female was first diagnosed with bloody diarrhea; colonoscopy showed left colitis and the biopsy was positive for ulcerative colitis. Her Mayo score was 9. She was offered and accepted the step down treatment. She was given infliximab 5mg/Kg of body weight at week 0...
Luminal concentrations of short chain fatty acids (SCFA), ammonia, sodium and potassium were measured in colonic dialysate of 16 control subjects and in 65 cases with ulcerative colitis (UC), which were graded according to mucosal changes into mild (1), moderate (2), or severe (3) inflammatory activity. Sodium concentrations were mildly but not significantly increased in severe ulcerative colitis while luminal potassium concentrations were markedly decreased in severe ulcerative colitis (p less than 0.025). Concentrations of SCFA were increased in severe ulcerative colitis. Butyrate concentrations were significantly raised in all stages of active ulcerative colitis even when other fatty acids were not raised. Of all the parameters a lowered pH and raised butyrate concentration most strikingly correlate with the severity of mucosal change. Results indirectly suggest that control of luminal pH, potassium secretion and utilisation of butyrate by the colonic mucosa are impaired with progressive mucosal inflammation.
A microtitre method was developed to screen Escherichia coli from 48 patients with ulcerative colitis and 25 controls for serum resistance. Bactericidal resistance was indicated by a change in colour of indicator due to acid production by viable organisms and quantitated by a change in absorbance. The method clearly differentiated between organisms confirmed as resistant or sensitive by conventional techniques. Twenty four (50%) disease and 14 (56%) control E coli specimens showed serum resistance. Bactericidal competence of sera from patients with ulcerative colitis was assessed by incubating sensitive E coli with sera from 10 patients with ulcerative colitis and pooled normal serum. All sera effectively reduced viable counts to less than 6% of original inoculum. This study shows that serum samples from patients with ulcerative colitis are bactericidally competent and that there is no increase in the number of serum resistant E coli in patients with ulcerative colitis.
Thirty-six patients underwent orthotopic liver transplantation (OLT) for primary sclerosing cholangitis under cyclosporine, azathioprine, and steroid immunosuppression. Of these patients, 29 suffered from chronic ulcerative colitis. The purpose of this study is to determine (1) whether replacement of the diseased liver and the altered immunocompetence suppresses the manifestation of chronic ulcerative colitis, and (2) if active colonic disease alters allograft function. Thirty of 36 patients survived OLT. After OLT, seven of 14 patients with symptomatic colon disease at the time of transplantation continue to suffer from active chronic ulcerative colitis, and three of 13 who were asymptomatic developed clinically active disease. Intractable colonic disease was the indication for post-OLT proctocolectomy in three patients, and one refused an indicated colectomy. Despite the long duration of the disease, none developed colonic malignancy. Long-term graft assessment showed good hepatocyte synthetic function in patients suffering from either active or inactive disease. Liver alkaline phosphatase, however, was significantly higher in patients suffering from active colonic disease. Furthermore, the alkaline phosphatase in symptomatic patients was higher than that seen in a matched cohort undergoing OLT for chronic active hepatitis or primary biliary cirrhosis. These results suggest that (1) liver replacement and immunosuppression in patients suffering from sclerosing cholangitis and ulcerative colitis do not alter the course of the colon disease...
A survey has been made of pregnancy occurring in patients who were attending the Ulcerative Colitis Clinic at Oxford during the 20-year period, 1960-79 inclusive. There were 256 married women of child-bearing age who attended during this period. Of these, 100 were excluded from the survey for various reasons, such as that they had completed their family before the onset of the ulcerative colitis, had already had an hysterectomy, or had a proctocolectomy before their first pregnancy. Of the remaining 156 patients, nine could not be traced. Full details were obtained from 147 patients, virtually all of whom were interviewed. The fertility of these patients was normal. Of the 147 women, 119 (81%) had conceived and only 10 (6·8%) were involuntarily infertile. The size of family approximated to that found in the general British population. The overall outcome of the pregnancies was similar to that in the general British population. The patients in whom the disease was quiescent at the start of pregnancy fared particularly well. Those with active disease had a somewhat lower chance of producing a normal live baby. The small group of patients in whom the disease was severe had a much lower chance of a normal outcome. Patients in whom the ulcerative colitis was quiescent at the beginning of pregnancy had a good chance of remaining symptom-free throughout the pregnancy and puerperium. Even if the colitis recurred...
Pressure activity in the rectum and anal canal was measured with a multilumen probe in 29 patients with ulcerative colitis (12 active, 11 quiescent, six studied during both phases) and 18 normal controls under resting conditions and during rectal infusion of saline. Resting motor activity was significantly decreased in patients with active colitis compared with quiescent colitis (p less than 0.005) and normal controls (p less than 0.001). Forty per cent of active colitics showed a featureless record compared with only one patient with quiescent colitis and one normal subject. The volume of saline infused before leakage occurred, and the total volume retained were significantly lower (p less than 0.001) in patients with active and quiescent colitis compared with normal controls. Rectal infusion of saline provoked regular rectal contractions, of significantly higher (p less than 0.05) amplitude in patients with active colitis, than in quiescent colitis or controls. These rectal contractions were associated with simultaneous anal relaxations. During saline infusion, peak and pressures were lower in patients with ulcerative colitis than in normal subjects, but there were no significant differences in relaxation pressures. In normal subjects...
Background—The course of inflammatory bowel
disease after liver transplantation has been reported as variable with
usually no change or improvement, but there may be an increased risk of early colorectal neoplasms. In many centres steroids are often withdrawn early after transplantation and this may affect inflammatory bowel disease activity. Aims—To evaluate the course of inflammatory bowel
disease in primary sclerosing cholangitis transplant patients who were
treated without long term steroids. Methods—Between 1989 and 1996, there were 30 patients transplanted for primary sclerosing cholangitis who survived
more than 12 months. Ulcerative colitis was diagnosed in 18 (60%)
patients before transplantation; two had previous colectomy. All
patients underwent colonoscopy before and after transplantation and
were followed for 38 (12-92) months. All received cyclosporin or
tacrolimus with or without azathioprine as maintenance immunosuppression. Results—Ulcerative colitis course after
transplantation compared with that up to five years before
transplantation was the same in eight (50%) and worse in eight (50%)
patients. It remained quiescent in eight and worsened in four of the 12 patients with pretransplant quiescent course...
The aetiology of ulcerative colitis is unknown. Two patients
without pre-existing inflammatory bowel disease in whom end colostomy for faecal incontinence was complicated by diversion colitis in the
defunctioned rectosigmoid colon, are described. In both instances, colitis with the clinical, colonoscopic, and microscopic features of
ulcerative colitis developed about a year later in the previously normal in-stream colon proximal to the colostomy. These cases suggest
that diversion colitis may be a risk factor for ulcerative colitis in
predisposed individuals and that ulcerative colitis can be triggered by
anatomically discontinuous inflammation elsewhere in the large intestine.
BACKGROUND—Chronic distal colitis may cause troublesome symptoms and alter quality of life. When medical treatment fails to control symptoms, patients and doctors are often reluctant to consider surgical resection because of the relatively small portion of the large bowel affected by the disease. AIM—To assess the outcome of restorative proctocolectomy (RP) in patients with distal colitis who required surgery for chronic debilitating symptoms and failed medical management. PATIENTS/METHODS—From 1986 to 1996, of 263 patients receiving RP for ulcerative colitis, 27 (16 men) were operated on for distal ulcerative colitis limited to the rectum and sigmoid colon. Bowel function and quality of life were compared before and one year after RP. RESULTS—The mean (SD) duration of ulcerative colitis was 11 (6) years. RP was performed at a mean age of 46 (10) years. All the pouches were J-shaped, and a diverting loop ileostomy was always performed. Mean (SD) hospital stay was 25 (10) days. Seven complications occurred in six patients. Previously unknown severe dysplasia was discovered on the colectomy specimen in two patients. After RP there was a significant decrease in mean (SD) daytime stool frequency (8.2 (4) v 4.7 (2)...
BACKGROUND AND AIMS—An association between the allele 2 of the interleukin 1 receptor antagonist gene variable number tandem repeats polymorphism in intron 2 and ulcerative colitis was first reported in 1994. Subsequent studies in Caucasian Northern European patients have not confirmed this, although trends towards an association were observed. The lack of statistical significance could reflect inadequate power. In this study the association was reassessed in a large independent set of well characterised Caucasian patients and a meta-analysis of reported patient series was performed. PATIENTS AND METHODS—A total of 320 patients with endoscopically and histologically confirmed ulcerative colitis (124 pancolitis, 196 left sided and distal disease) and 827 ethnically matched controls were genotyped at polymorphic sites in the interleukin 1 receptor antagonist gene. Carriage rates were compared using χ2 statistics. A meta-analysis of this and seven previous studies in North European Caucasian patients was performed using the Mantel-Haenszel χ2 test. RESULTS—Patients had a significantly increased carriage rate of allele 2 compared with controls (52% v 45%; odds ratio 1.3 (95% confidence interval (CI) 1.01-1.7); p=0.04). The allele 2 carriage rate was highest in extensive colitis (carriage rate 56%; odds ratio 1.5 (95% CI 1.1-2.3) p=0.02) and in individuals who had undergone colectomy (carriage rate 55%; odds ratio 1.5 (95% CI 0.95-2.4); p=0.08). Meta-analysis of all eight studies showed a significant association between carriage of allele 2 and ulcerative colitis (odds ratio 1.23 (95% CI 1.04-1.45); p=0.01). CONCLUSIONS—The association of the interleukin 1 receptor antagonist gene polymorphism with ulcerative colitis is confirmed. The association is minor and confers only a small risk to an individual but will contribute a high attributable risk in a population due to the high allelic frequency. Accurate phenotypic characterisation defines more homogeneous subsets of patients...
Background—Patients with ulcerative colitis have
an increased risk of colorectal cancer. Duration, age, and extent of
the disease at diagnosis are the only established risk factors.
Patients with ulcerative colitis and concomitant primary sclerosing
cholangitis (PSC) have been reported to have a higher frequency of
colonic DNA aneuploidy and/or dysplasia than expected, findings
indicating an increased risk of colorectal cancer compared with other
patients with ulcerative colitis. Methods—A population based cohort consisting of
125 patients with a verified diagnosis of PSC was followed up by
linkage to the Swedish Cancer Registry for the occurrence of colorectal cancer. Results—There were 12 colorectal cancers. Six
cancers were diagnosed prior to the diagnosis of PSC. Among the 104 patients with an intact colon at the time of the diagnosis of PSC there was a cumulative risk for colorectal cancer of 16% after 10 years. Among the 58 patients with a diagnosis of ulcerative colitis and colorectal cancer prior to the diagnosis of PSC, there were five colorectal cancers corresponding to a cumulative risk of 25% after 10years. Conclusions—Patients with ulcerative colitis and
concomitant PSC seem to constitute a subgroup with a high risk for
Thirteen sera from children with ulcerative colitis were examined for antibodies reacting with constituents of human colonic tissue by means of immunofluorescent methods. 3 out of 10 sera reacted positively when tested by the direct staining method while 6 out of 13 reacted positively when tested by the indirect method with conjugates of rabbit anti-human gamma globulin. The specificity of the reactions could be confirmed by inhibition tests. 16 sera from healthy children and adults yielded completely negative results. The staining capacity of various sera was correlated to their hemagglutinating titer when they were tested with sheep erythrocytes, coated with phenol-water extract of human colon. Absorption experiments indicated that the stainable antigen was also present in the extracts used for the hemagglutination experiments. In unfixed tissue sections, fluorescent antibodies were adsorbed onto the epithelial cells of the mucosa. Adsorption on epithelial basement membranes could not be demonstrated. Fluorescent H agglutinins, isolated from eel serum, were adsorbed onto the same mucosal structures of human colon (blood group O) as the antibodies in the sera of patients with ulcerative colitis. However, any immunological relationship between H substance and the colonic antigen of ulcerative colitis could be ruled out by cross-inhibition and hemagglutination inhibition experiments. Fluorescent serum from patients with rheumatoid arthritis also stained sections of human colon but the localization of the stainable antigens was different from that visualized with the ulcerative colitis sera. Inhibition experiments indicated that the rheumatoid arthritis serum contained antibodies staining colon antigens different from those reacting with antibodies in the ulcerative colitis sera. Sera from patients with systemic lupus erythematosus or with the nephrotic syndrome...
Interferons play critical roles in tumor pathogenesis by controlling apoptosis and through cellular anti-proliferative and differentiation activities. Interferon inducible transmembrane protein (IFITM) family genes have been implicated in several cellular processes such as the homotypic cell adhesion functions of IFN and cellular anti-proliferative activities. Expression levels of IFITM genes have been found to be up-regulated in gastric cancer cells and colorectal tumors. IFITM3 (also known as 1-8U) is a member of the IFITM family, and has been described as a key player in specification of germ cell fate. IFITM3 was first isolated from a genetic screen aimed at identifying genes involved in acquisition of germ cell competence. It has been proposed that epiblast cells have the highest expression of IFITM3 initiated germ cell specification and that homotypic association can discriminate germ cells from their somatic neighbors. In an attempt to better understand the genetic influences of IFITM3 on ulcerative colitis, we have identified possible variation sites and single nucleotide polymorphisms (SNPs) through two exons and their boundary IFITM3 intron sequences including the ~2.1 kb promoter regions. To determine whether or not these IFITM3 SNPs are associated with susceptibility to ulcerative colitis...
The treatment of ulcerative colitis has changed over the last decade, with the introduction of biological drugs. This article reviews the currently available therapies for ulcerative colitis and the specific use of these therapies in the management of patients in different settings, particularly the difficult-to-treat patients. The focus of this review is on adalimumab, which has recently obtained approval by the European Medicines Agency and the US Food and Drug Administration, for use in treating adult patients with moderate-to-severe, active ulcerative colitis, who are refractory, intolerant, or who have contraindications to conventional therapy, including corticosteroids and thiopurines. Since the results emerging from the pivotal trials have been subject to some debate, the aim of this review was to summarize all available data on the use of adalimumab in ulcerative colitis, focusing also on a retrospective series of real-life experiences. Taken together, the current evidence indicates that adalimumab is effective for the treatment of patients with different types of ulcerative colitis, including biologically naïve and difficult-to-treat patients.
Fonte: Universidade Nacional da AustráliaPublicador: Universidade Nacional da Austrália
Tipo: Journal article; Published VersionFormato: 21 pages
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produced by intestinal goblet cells is the major component of the intestinal
mucus barrier. The inflammatory bowel disease ulcerative colitis is characterized by depleted
goblet cells and a reduced mucus layer, but the aetiology remains obscure. In this study we
used random mutagenesis to produce two murine models of inflammatory bowel disease,
characterised the basis and nature of the inflammation in these mice, and compared the
pathology with human ulcerative colitis.
METHODS AND FINDINGS:
By murine N-ethyl-N-nitrosourea mutagenesis we identified two distinct noncomplementing
missense mutations in Muc2 causing an ulcerative colitis-like phenotype. 100% of mice of both
strains developed mild spontaneous distal intestinal inflammation by 6 wk (histological colitis
scores versus wild-type mice, p , 0.01) and chronic diarrhoea. Monitoring over 300 mice of
each strain demonstrated that 25% and 40% of each strain, respectively, developed severe
clinical signs of colitis by age 1 y. Mutant mice showed aberrant Muc2 biosynthesis, less stored
mucin in goblet cells, a diminished mucus barrier, and increased susceptibility to colitis induced
by a luminal toxin. Enhanced local production of IL-1b, TNF-a...
Collagenous colitis and ulcerative colitis are distinct disorders. A 67 year old woman with clinical and histological evidence of collagenous colitis had an abrupt symptomatic exacerbation while taking anti-inflammatory treatment with sulphasalazine and prednisone. Repeat colorectal endoscopy showed active mucosal inflammation and colonic biopsy specimens were consistent with active ulcerative colitis. After bowel rest, total parenteral nutrition, intensification of the anti-inflammatory regimen, and withdrawal of non-steroidal anti-inflammatory drugs (which she had taken continuously for osteoarthritis) diarrhoea abated. Colorectal biopsy specimens obtained when the patient's symptoms had improved showed inactive ulcerative colitis with no evidence of collagenous colitis. This may be the first case to be reported of the metachronous association of collagenous and ulcerative colitis.
OBJECTIVE: The purpose of this study was to determine whether there is an association between Crohn's disease and ulcerative colitis with MLH1. SUMMARY BACKGROUND DATA: Identification of genes involved in the etiology of inflammatory bowel disease may lead to the development of markers that objectively can define disease and permit therapy. The treatment of Crohn's disease of the colon and ulcerative colitis also is complicated by difficulties in differentiating the two conditions. METHODS: The DNA and clinical data were obtained on 126 unrelated individuals (45 Crohn's disease, 36 ulcerative colitis, and 45 control subjects without intestinal disease). Polymerase chain reaction products were analyzed by single-strand conformation polymorphisms (MLH1 exons 9, 11, 14, 15, and 16) and polyacrylamide gel electrophoresis (markers D3S1611 and D3S1768). All comparisons were analyzed by chi square test. The association between single haplotypes and disease was expressed as relative odds. RESULTS: MLH1 exons 9, 11, 14, and 16 were monomorphic. Two, four, and six alleles were detected in MLH1 exon 15, D3S1611, and D3S1768, respectively. Significant associations were observed for MLH1 exon 15/D3S1611 haplotypes AB (OR = 5.5; p = 0.007) and BA (p = 0.002) with Crohn's disease and for haplotypes AB (OR = 4.0; p = 0.042)...
Skin reactivity to dinitrochlorobenzene (DNCB) and levels of circulating T-lymphocytes were measured in 15 patients with ulcerative colitis, 15 patients with Crohn's disease, and 12 normal control subjects. Diminished reactivity to DNCB was demonstrated in 87% of patients with Crohn's disease (P less than 0-001) and in 53% with ulcerative colitis (P less than 0-02), as compared with only 8-5% of controls; anergy was more frequent in Crohn's disease than in ulcerative colitis (P less than 0-05). Levels of circulating T-lymphoctes were also depressed in both Crohn's disease and ulcerative colitis (P less than 0-001) as compared with controls, with the values lower in Crohn's disease than in ulcerative colitis (P less than 0-02). There were no correlations of DNCB response with extent, duration, or severity of disease nor with T-cell levels within any patient group. These data provide further support for the concept that there is impairment of cell-mediated immunity among many patients with chronic inflammatory bowel disease, including both Crohn's disease and ulcerative colitis.
Thirty five adult patients with precirrhotic primary sclerosing cholangitis were randomly allocated to treatment for at least one year with low dose (4.1 mg/kg/day) cyclosporin or placebo in a double blind trial. Thirty patients had coexisting ulcerative colitis, including three who had previously undergone colectomy and one who discontinued treatment after three months. Of the remaining 26 patients, 16 received cyclosporin and 10 received placebo. Endoscopy was performed at entry to confirm the diagnosis of inflammatory bowel disease. The ulcerative colitis disease activity was prospectively classified annually as remission/mild, moderate, or severe using the Truelove and Witt's criteria. Before treatment there were no differences between the cyclosporin and placebo groups in the number of patients with remission/mild colitis, 14/16 (88%) v 9/10 (90%), and moderate colitis, 2/16 (12%) v 1/10 (10%). During treatment, a remission/mild disease course was present in 15/16 (94%) v 6/10 (60%), p = 0.05 and a moderate disease course in 1/16 (6%) v 4/10 (40%), p = 0.05. It is concluded that patients treated with cyclosporin for primary sclerosing cholangitis who have coexisting ulcerative colitis have a more benign course of colitis resulting both from improvement of moderately active colitis and from fewer flares of remission/mildly active colitis. These findings suggest that cyclosporin may be of benefit to the colon in patients with ulcerative colitis who are being treated with cyclosporin for primary sclerosing cholangitis.
The perpetuation of inflammation in ulcerative colitis and Crohn's disease may be regulated in part by an increased secretion of proinflammatory cytokines due to either an appropriate response to initial stimulating agents, and/or due to an impaired down-regulation of cytokine secretion. The aim of this study was to determine the secretion patterns of the proinflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), IL-6 and IL-1 beta, from isolated lamina propria mononuclear cells (LPMNC) isolated from colonic biopsies from patients with untreated ulcerative colitis or Crohn's disease. LPMNC isolated from involved inflammatory bowel disease (IBD) mucosa spontaneously produced increased amounts of TNF-alpha, and IL-6, and IL-1 beta. The TNF-alpha secretion from IBD LPMNC could be further enhanced by pokeweed mitogen stimulation. The secretion patterns of TNF-alpha and IL-1 beta by LPMNC from patients with either ulcerative colitis or Crohn's disease demonstrated a close correlation with the degree of tissue involvement and mucosal inflammation. LPMNC from non-involved ulcerative colitis mucosa secreted markedly increased levels of IL-6 compared with non-involved Crohn's disease mucosa or control mucosa. The heightened IL-6 secretion from LPMNC from non-involved ulcerative colitis mucosa without visible or microscopic signs of inflammation indicates that the pathophysiologic mechanisms involved in the initiation of inflammation may differ between ulcerative colitis and Crohn's disease. The determination of proinflammatory cytokine secretion by isolated LPMNC from colonoscopic biopsies may be a sensitive method for monitoring the severity of mucosal inflammation in IBD patients.