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PubMed1999

Fertility after ileal pouch-anal anastomosis in women with ulcerative colitis.

BACKGROUND: Women with ulcerative colitis are believed to have normal fertility but colectomy and ileal pouch-anal anastomosis (IPAA) may impair fertility. The aim was to compare fertility in patients with ulcerative colitis before and after IPAA with that in the national population. METHODS: Some 258 consecutive women who had undergone IPAA for ulcerative colitis were identified. Data were collected by questionnaire and from medical records. The observed number of births was compared with the number expected by indirect standardization by age and calendar year. Fertility from the age of 15 years to colectomy, from the onset of ulcerative colitis to colectomy, and from the 12 months after stoma closure to the time of data collection was investigated. RESULTS: A total of 237 women (92 per cent) responded. From the age of 15 years to colectomy there were 251 deliveries compared with an expected number of 286 (P < 0. 05). The number of births from the onset of ulcerative colitis to colectomy was 120, compared with an expected 131 (P > 0.3). From the 12 months after ileostomy closure until data collection there were 34 deliveries, compared with an expected 69 (P < 0.001). CONCLUSION: There is a considerable reduction in postoperative fertility after restorative surgery for ulcerative colitis.

Adult↗
PubMed2001

Evolving medical therapies for ulcerative colitis.

Patients with ulcerative colitis have traditionally relied on sulfasalazine, mesalamine, and corticosteroids as the mainstay of medical therapy. Steroid-refractory, -dependent, or -intolerant patients have resorted to agents such as cyclosporine for short-term efficacy and 6-mercaptopurine or azathioprine for long-term efficacy. The next generation of evolving therapies includes many novel agents that target various aspects of the human immune response. Therapies that block the production or action of tumor necrosis factor have received much interest in inflammatory bowel disease. Treatments currently under study include interleukins, interferons, T-cell selective antibodies, molecules involved in cellular trafficking and signaling, mucosal healing or growth factors, and novel steroid agents. Other "less traditional" therapies, including probiotics, heparins, and anti-gastric ulcer remedies, challenge our understanding of the pathogenesis of ulcerative colitis and may provide further insights into future therapies.

Colitis, Ulcerative↗
PubMed2005

Expression of apoptosis related proteins during malignant progression in chronic ulcerative colitis.

BACKGROUND: Chronic ulcerative colitis (CUC) is associated with increased risk of developing colon cancer through a dysplasia (intraepithelial neoplasia)-carcinoma sequence. AIMS: To investigate the expression of apoptosis and inflammatory related proteins in CUC. METHODS: The expression of proteins involved in apoptosis and inflammation (inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), Bcl-xl, Fas, and active caspase 3) was investigated and compared with that seen in sporadic colon carcinoma. RESULTS: COX-2 was negative in the epithelium of all samples. iNOS was clearly present in inflammatory areas in CUC epithelium, weakly expressed in dysplasia, and absent or weakly expressed in tumour cells. Bcl-xl was absent in CUC, increased in dysplasia, and highly expressed in most carcinomas. Fas expression was positive in the surface epithelium of CUC, dysplasia, and most tumour cells. Activated caspase 3 was weakly positive in all samples, indicating limited apoptosis. Compared with CUC associated carcinoma, iNOS was consistently expressed in sporadic colon carcinoma cells, whereas Bcl-xl was almost absent in these tumour cells and Fas was only weakly expressed. Activated caspase 3 was present in normal mucosal samples and some tumour cells. CONCLUSION: Apoptosis related proteins--particularly iNOS, Bcl-xl, and Fas-show a distinct pattern of expression in the CUC to carcinoma sequence, which differs from that seen in sporadic carcinoma, but bears a striking resemblance to that seen during neoplastic progression in Barrett's oesophagus. These results support a causal role for chronic inflammation in cancer development in CUC, and treatment of ulcerative colitis should aim to minimise inflammation.

Adenocarcinoma↗
PubMed1998

Substance P and vasoactive intestinal polypeptide but not calcitonin gene-related peptide concentrations are reduced in patients with moderate and severe ulcerative colitis.

BACKGROUND AND AIMS: Ulcerative colitis is a chronic inflammatory condition characterized by an altered intestinal immunoinflammatory response. Since increasing evidence indicates that neuropeptides play a key role in the regulation of gastrointestinal immune function, the aims of this study were: a) to determine tissue and plasma levels of Vasoactive Intestinal Polypeptide, Substance P, and Calcitonin Gene-Related Peptide in patients with ulcerative colitis, and b) to ascertain whether a relationship exists between tissue concentrations of neuropeptides and the histological grading of mucosal inflammation. METHODS: A total of 29 patients with active and 39 with inactive ulcerative colitis, and 16 control subjects took part in the study. Biopsy specimens of colonic mucosa and blood samples were obtained from each subject, and neuropeptide concentrations were measured by sensitive and specific radioimmunoassays. RESULTS: Both Vasoactive Intestinal Polypeptide and Substance P concentrations were found to be significantly reduced in endoscopic biopsy specimens of patients with ulcerative colitis compared to controls (p < 0.01 and p = 0.05, respectively), and the reduction appeared to be related to the degree of mucosal inflammation; in contrast, Calcitonin Gene-Related Peptide tissue levels were unchanged. In addition, there was no significant difference in the neuropeptide plasma levels between ulcerative colitis patients and control subjects. CONCLUSIONS: Taken together, our results suggest that the reduction of Vasoactive Intestinal Polypeptide and Substance P is probably a secondary phenomenon, correlated with the degree of mucosal inflammation; whatever the mechanism, the decreased availability of these neuropeptides in the local microenvironment may play an important role in the pathogenesis of ulcerative colitis, by affecting many components of the normal immune response. Moreover, based on our data, the measurement of neuropeptide plasma concentrations does not appear to be a useful tool to monitor disease activity.

Adult↗
PubMed2005

Patient defined dichotomous end points for remission and clinical improvement in ulcerative colitis.

BACKGROUND AND AIMS: Ulcerative colitis disease activity indices offer good statistical power but small changes in these indices may not be clinically important. There are no validated definitions of remission or of significant improvement for these indices. The use of clinically important end points would strengthen the validity of study outcomes. Our aims were to identify objective end points in standard disease activity indices for remission and for improvement in ulcerative colitis. METHODS: Sixty six consecutive patients with ulcerative colitis provided information about remission status and their disease activity. At a return visit 1-14 months later, these patients provided information about the change in their disease activity, and non-invasive indices were measured. RESULTS: Specific objective end points for determining remission with four standard indices and a quality of life instrument were determined (St Mark's <3.5, ulcerative colitis disease activity index <2.5, simple clinical colitis activity index (SCCAI) <2.5, Seo <120, and inflammatory bowel disease quality of life index (IBDQ) >205). These cut offs also identified patients who met a regulatory definition of remission. Specific objective end points for clinical improvement in two non-invasive indices and a quality of life instrument were determined with good sensitivity and specificity (SCCAI decrease >1.5, Seo decrease >30, IBDQ increase >20). CONCLUSIONS: We found specific cut off values for disease activity indices that identify patients who have significantly improved or achieved remission in an objective, sensitive, and specific manner. These cut offs should help in the interpretation of the outcomes of clinical trials in ulcerative colitis.

Adult↗
PubMed1986

Variation in the argyrophil cell population of the rectum in ulcerative colitis and adenocarcinoma.

Longstanding ulcerative colitis predisposes to carcinoma of the colon. Argyrophil cell hyperplasia has been observed in association with dysplasia and neoplasia in ulcerative colitis. As the argyrophil cell population includes those cells producing enterglucagon, a hormone thought to stimulate mucosal proliferation, this study was designed to determine whether there was any consistent variation in the argyrophil cell population in longstanding ulcerative colitis. Argyrophil cells were demonstrated by the Grimelius method of silver impregnation in sections of non-tumour bearing mucosa from the rectosigmoid colon of normal bowel, ulcerative colitis with and without tumour, and mucosa adjacent to, and distant from, carcinoma arising in otherwise normal bowel. Cell numbers were expressed as ratios of argyrophil cells per crypt, per mm of epithelium, and per mm of underlying muscularis mucosae. There was marked individual variation within all groups in all parameters. Between groups, the only significant difference was an increase in argyrophil cells per crypt in ulcerative colitis. The significance of this finding is discussed.

Adenocarcinoma↗
PubMed1997

Cytomegalic colitis after total colectomy in ulcerative colitis: report of a case.

A 58-year-old man with ulcerative colitis underwent total colectomy and ileorectal anastomosis. Steroid suppositories were administered postoperatively, and he had had no exacerbation in the residual rectum for 12 years. He suddenly presented with frequent bloody stools and anal pain. An intensive intravenous regimen of prednisolone was ineffective. Cytomegalic inclusion bodies were identified in biopsy specimens. Administration of ganciclovir reduced the ulcers remarkably. The clinical course suggested that this deterioration was caused by cytomegalovirus infection from the beginning. Cytomegalovirus colitis should be recognized as an exacerbating factor, even in ulcerative colitis patients who have undergone surgery, especially when the residual bowel inflammation is resistant to steroid therapy.

Colitis↗
PubMed2006

Pit patterns in rectal mucosa assessed by magnifying colonoscope are predictive of relapse in patients with quiescent ulcerative colitis.

BACKGROUND: Relapse of ulcerative colitis is difficult to predict by routine colonoscopy. A high-resolution video-magnifying colonoscope with chromoscopy enables the observation of colorectal mucosal pit patterns. AIMS: To investigate the association of pit patterns as assessed by magnifying colonoscopy (MCS) with histological inflammation and mucosal chemokine activity in patients with quiescent ulcerative colitis, and to prospectively analyse the prognostic factors that may predict exacerbations. METHODS: MCS was performed in 113 patients with ulcerative colitis in remission. Pit patterns in the rectal mucosa were classified into four MCS grades on the basis of size, shape and arrangement. Mucosal interleukin (IL) 8 activity was measured in biopsy specimens of rectal mucosa and the specimens were assessed for histological disease activity. The patients were then followed until relapse or for a maximum of 12 months. Multivariate survival analysis was carried out to determine the independent predictors of clinical relapse. RESULTS: A positive correlation was identified between MCS grade, histological grade (p = 0.001) and mucosal IL8 activity (p<0.001). Multivariate proportional hazard model analysis showed that MCS grade was a significant predictor of relapse (relative risk 2.06, p = 0.001). Kaplan-Meier estimate of relapse during 12 months of follow-up was found to increase with increasing MCS grade, with values of 0% for grade 1, 21% for grade 2, 43% for grade 3 and 60% for grade 4. CONCLUSION: MCS grading is associated with the degree of histological inflammation and mucosal IL8 activity in patients with quiescent ulcerative colitis, and may predict the probability of subsequent disease relapse in patients with ulcerative colitis in remission.

Adolescent↗
PubMed2006

Probiotics modulate inflammatory cytokine secretion from inflamed mucosa in active ulcerative colitis.

Enteric microflora of ulcerative colitis patients becomes aberrant. The abnormal interaction between microflora and intestinal mucosal immune system leads the mucosal inflammation. Probiotic administration may recover the commensal microflora and normalise the host-microbial interaction. In this experiment, we cocultured colonic biopsies from active ulcerative colitis patients with bifidobacterium to investigate the modulation effect of probiotics on inflamed colonic tissues and its possible mechanism. Colonic biopsies from active ulcerative colitis were cocultured for 24 h with Bifidobacterium longum. Tumour necrosis factor (TNF)-alpha and interleukin (IL)-8 in supernatants were measured using enzyme-linked immunosorbent assays, the biopsies were fixed using paraffin and the expression of NF-kappaB P65 of tissues was studied using immunohistochemical staining. The concentrations of TNF-alpha and IL-8 in supernatants of tissues cocultured with probiotics were lower than those cultured alone. The number of lamina propria mononuclear cells (LPMC) with nuclear factor-kappa B (NF-kappaB) P65 positive in cocultured tissues was also decreased. When cocultured with inflamed tissues of active ulcerative colitis, probiotics could inhibit NF-kappaB activation in LPMC and down-regulate inflammatory cytokine secretion from inflamed tissues of active ulcerative colitis.

Adolescent↗
PubMed1999

Colorectal cancer complicating ulcerative colitis: an institutional series.

Ulcerative colitis predisposes to colorectal cancer: the risk increases along with disease duration and extension. Also some subsets of patients are at increased risk, namely patients with early onset of colitis, and patients with primary sclerosing cholangitis. Cancer complicating ulcerative colitis affects evenly all the colon, and is not located more frequently in the rectum and in the sigmoid colon, as well as the sporadic counterpart. Multiple cancers and cancers associated with high grade dysplasia are not infrequent in ulcerative colitis; for this reason, and for controlling the colitis, the treatment of choice is total colectomy, with or without colostomy. The prognosis of cancer complicating ulcerative colitis is similar to the sporadic counterpart. The Authors present a colon cancers series as a complication of colitis occurred at Regina Elena Cancer Institute of Rome, Italy, over the period 1975-1998.

Adult↗
PubMed1999

Amino acid polymorphism at residue 71 in HLA-DR beta chain plays a critical role in susceptibility to ulcerative colitis.

The association of ulcerative colitis with distinct HLA-DRB1 alleles has not been easy to ascertain. Recent studies show that among HLA-DR2 alleles, DRB1*15 but not DRB1*16, is associated with the disease. Similarly, in the HLA-DR1 group, only DRB1*0103 is increased in ulcerative colitis patients. The aim of our study was to identify critical DRB1 residues that might account for these differences. We typed 121 patients with ulcerative colitis and 275 controls using gene amplification and sequence-specific oligonucleotide probing for HLA-DRB1 and DRB3. We observed a strong negative association between HLA-DRB1 alleles that encode lysine at position 71 in their beta-chain and susceptibility to ulcerative colitis. Differences in the prevalence among other alleles differing only in the third hypervariable region suggested a hierarchy of susceptible and protective class II alleles related to the presence of an acidic, neutral, or basic amino acid residue at position 71. These data implicate most strongly the amino acid residues in the third hypervariable region of the DRbeta chain, especially DRbeta71, in the association between ulcerative colitis and HLA. However, this does not exclude the contribution of other parts of the molecule and other immunoregulatory genes.

Adult↗
PubMed1997

Familial and psychological risk factors of ulcerative colitis.

BACKGROUND: The aetiology of ulcerative colitis is still unknown. Several theories have been proposed taking into account psychological influences. AIMS: The present study was undertaken to test the hypothesis of a relationship between certain individual psychological patterns, stress, some familial variables, and ulcerative colitis. PATIENTS: A series of 122 patients with ulcerative colitis and a matched hospital control population were independently studied by a team of physicians and a team of psychologists. METHODS: State-Trait Anxiety Inventory (Form Y) and Sacks' sentence completion tests were submitted to all subjects in both populations. RESULTS: Data showed significantly higher anxiety trait and state in ulcerative colitis patients, whilst 84% of ulcerative colitis patients showed a variety of obsessional traits and an affectivity state characterized by introversion and emotional immaturity. A link was found with regard to relationship with mother, to the condition of single children in the male ulcerative colitis population (41% vs 18% controls), and to last born daughters in the female ulcerative colitis group (47.5% vs 27.9% controls). In addition, a previous stressful life event within the 12-month period prior to the investigation was found in 44.3% of ulcerative colitis patients and in 10.7% of controls. CONCLUSIONS: Psychological disturbances and familial condition are proposed as risk factors, if not actual aetiological variables of ulcerative colitis.

Adult↗
PubMed1980

Ulcerative colitis and its treatment.

Ulcerative colitis and its epidemiology, etiology, pathophysiology, diagnosis, clinical findings, complications, treatment, and prognosis are reviewed. Ulcerative colitis, an inflammatory disease of unknown origin that varies in severity and clinical course, occurs most often in patients 30 to 70 years old. It appears to have a genetic component and to involve the immunological system. The cardinal symptom is usually bloody diarrhea, and the disease may be classified by either the severity of an attack, the clinical course, or by anatomic localization of inflammation. Initial treatment of ulcerative colitis generally includes corticosteroids administered either rectally, orally, or parenterally. Oral sulfasalazine has been found useful in treating this condition and is often used for prolonged therapy to prevent relapses. Azathioprine, cromolyn sodium, antidiarrheal/anticholinergic agents, and nutritional supplements are used at times. Surgery is indicated under certain conditions and usually involves panproctocolectomy with permanent ileostomy. The prognosis of ulcerative colitis depends upon the age of the patient, the extent of colonic involvement, and the severity of the attach.

Adrenal Cortex Hormones↗
PubMed2005

Cancer surveillance in ulcerative colitis.

BACKGROUND: Patients with ulcerative colitis are at a higher risk of developing colorectal cancer than those without the disease. Surveillance programmes are used routinely to detect dysplasia and cancer in patients with ulcerative colitis. However, such programmes are poorly effective. This article discusses possible improvements suggested by recent research. METHODS: Papers relating to cancer associated with ulcerative colitis and surveillance programmes to detect such cancer were identified using Medline searches. Further papers were identified from the reference lists of identified papers. RESULTS: The probability of cancer for all patients with ulcerative colitis regardless of disease extent was 2 per cent at 10 years, 8 per cent at 20 years and 18 per cent at 30 years; the overall prevalence of colorectal cancer in any patient was 3.7 per cent. Indications for colonoscopic surveillance are extensive disease for 8-10 years, especially in those with active inflammation, a family history of colorectal cancer and primary sclerosing cholangitis. Problems affecting surveillance include the diagnosis of dysplasia, difficulty in differentiating 'sporadic' adenomas from a dysplasia-associated lesion or mass, and decision making based on surveillance findings. Molecular genetic and endoscopic advances to alleviate these problems are discussed. CONCLUSION: Rates of detection of dysplasia can be improved by chromoendoscopy. Molecular genetics has the potential to identify patients most at risk of cancer and can differentiate between different types of lesion.

Aneuploidy↗
PubMed2002

Depletion of non specific esterase activity in the colonic mucosa of patients with ulcerative colitis.

BACKGROUND: Non specific esterases (NSE) are a group of cellular carboxylesterases, enzyme markers of monocytes/macrophages, whose tissue distribution in the human body and changes in various disease states have not been adequately studied. We investigate the presence and localization of NSE, in the normal and inflamed human colonic mucosa. DESIGN: NSE were studied histochemically and biochemically using alpha-naphthyl acetate as the substrate, in the colonic mucosa from 67 patients with colitis of various aetiologies and 10 normal controls. In addition, esterase activity was studied biochemically in serum from colitic patients and normal controls. RESULTS: Histochemical study of the colonic tissue demonstrated that NSE were localised in the epithelial brush border, the goblet cells of the glands and a macrophage population of the lamina propria in the colonic mucosa of normal controls and patients with non specific colitis. In active ulcerative colitis, esterase depletion and esterase negative macrophages were identified in parallel with goblet cell disappearance. Gradual reappearance of esterase activity was found after successful treatment. Biochemical study of NSE activity showed that serum and colonic tissue esterase levels were greatly (P < 0.001) reduced in active ulcerative colitis compared to the normal controls or non specific colitis patients and they were increased after successful treatment. Despite this increase, the esterase activity in the colonic tissue from ulcerative colitis patients after treatment was significantly reduced compared to the normal controls. Interestingly, the enzyme levels from non-inflamed areas of the bowel of patients with ulcerative colitis were also significantly (P < 0.01) decreased compared to the normal controls. CONCLUSIONS: These data suggest that esterase reduction in ulcerative colitis is not a simple result of the inflammatory process but rather it precedes its development. This enzyme depletion might have an important pathogenetic implication in the inflammatory process.

Adult↗
PubMed1998

Fecal hydrogen sulfide production in ulcerative colitis.

OBJECTIVE: Sulfide, a product of sulfate-reducing bacteria, has been proposed to play an etiologic role in ulcerative colitis. Ulcerative colitis feces have increased numbers and activity of sulfate-reducing bacteria, but only modestly increased sulfide. However, fecal sulfide exists largely in the volatile, highly toxic H2S form that moves rapidly from feces to surrounding gas. Our aim was to quantify the fecal release of H2S and other volatiles (CO2, H2, CH4, methanethiol, and dimethylsulfide). METHODS: Fecal samples from 25 subjects with ulcerative colitis and 17 controls were incubated in 4-L containers, and gas release was assessed at intervals over 24 h. RESULTS: H2S release by ulcerative colitis feces was elevated 3-4-fold at every measurement point compared with normal feces (p < 0.003 at 24 h). The only other significant difference was increased CO2 release by ulcerative colitis feces at 1 h. Supplementation of fecal homogenates with sulfur-containing substrates showed that organic compounds (mucin, cysteine, taurocholate) provided more readily utilizable substrate for H2S production than did sulfate. CONCLUSIONS: Increased H2S release is a relatively localized metabolic aberration of ulcerative colitis feces. This increased H2S may reflect abnormalities of the fecal bacteria and/or substrate availability.

Adolescent↗
PubMed2001

Low-dose low-molecular weight heparin (enoxaparin) is effective as adjuvant treatment in active ulcerative colitis: an open trial.

Ulcerative colitis is a chronic inflammatory bowel disorder of unknown etiology. Treatment of flare-ups is based on mesalamine and steroids. Treatment of moderate to severe ulcerative colitis with high-dose heparin and low-molecular-weight heparin was reported. The mechanism was assumed to be a combination of anti-coagulant and anti-inflammatory effects. Low-molecular-weight heparin is better and safer than unfractionated heparin. Studies of low-dose low-molecular-weight heparin in experimental models of inflammation and in inflammatory diseases demonstrated a beneficial effect. Our aim in this study was to evaluate the effect of low-dose, low-molecular-weight heparin in active ulcerative colitis. Twelve patients with flare-ups of colitis were prospectively enrolled. Subcutaneous injections of 5-mg enoxaparin were administered at weekly intervals for 12 weeks. Mesalamine doses remained unchanged. Clinical, laboratory, endoscopic, histologic, and quality-of-life scores were evaluated at the beginning and end of the study. Ten patients completed the study. Mean age was 40.1; the female-male ratio was 7:3. Mean Mayo scores were 9.0 +/- 0.94 at baseline and 3.4 +/- 2.0 at the end of the study (P = 0.0001). Endoscopic scores decreased from 2.2 +/- 0.4 to 1.2 +/- 1.0 (P = 0.049) and in 7 of 10 patients extent of disease shortened. A significant increase in IBDQL scores from 135.7 +/- 37.17 to 179.6 +/- 45.15 points was demonstrated (P = 0.0117). Adverse events were one hospitalization due to abdominal pain, arthralgia (1), transient peripheral edema (1), and elevation of alkaline phosphatase (1). During follow-up, one patient required colectomy and another experienced an exacerbation. In conclusion, low-dose low-molecular-weight heparin once a week, combined with mesalamine, may be an effective therapy for active ulcerative colitis. It may delay or preclude the need for steroid treatment. Controlled studies to evaluate efficacy are needed.

Adult↗