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PubMed1995

Microscopic colitis syndrome.

The colorectal biopsy specimens from 30 patients with chronic watery diarrhoea but normal endoscopic and radiographic findings were studied by light microscopy, morphometry, immunohistochemistry, and two patients with electron microscopy. The histological changes in the colorectum were originally diagnosed in six patients as lymphocytic colitis and in 24 patients as collagenous colitis. The analysis of the specimens for this study could delineate three distinct groups of microscopic colitis: lymphocytic colitis (six patients), collagenous colitis without lymphocytic attack on the surface epithelium (seven patients), and a mixed form presenting with both thickening of the collagen plate and increased number of intraepithelial lymphocytes (17 patients). No transformation was seen from one type to another during follow up of six patients for four to seven years. Increased numbers of active pericryptal myofibroblasts were found with the electron microscope in one patient with mixed microscopic colitis showing also myofibroblasts entrapped within the collagen layer. Hitherto undescribed flat mucosa of the ileum was found in one patient with lymphocytic colitis and both flat mucosa and thickening of the collagen plate in the ileum were seen in one patient with the mixed form of the disease. In another patient with mixed microscopic colitis, normalisation of the colorectal morphology occurred after temporary loop ileostomy, followed by the reappearance of both diarrhoea, inflammation, and thickening of the collagen plate after the ileostomy was reversed. No association was found between non-steroid anti-inflammatory drug (NSAID) consumption and collagenous or mixed microscopic colitis. The primary cause of microscopic colitis is probably an immunological reaction to luminal antigen/s, perhaps of ileal origin. The engagement of the pericryptal myofibroblasts in the disease process might result in the development of the various forms of microscopic colitis. An inverse relation between intraepithelial lymphocyte count and collagen thickness may indicate that microscopic colitis is a spectral disease.

Adult↗

PubMed2006

Agonists of cannabinoid receptor 1 and 2 inhibit experimental colitis induced by oil of mustard and by dextran sulfate sodium.

Oil of mustard (OM) is a potent neuronal activator that is known to elicit visceral hyperalgesia when given intracolonically, but the full extent to which OM is also proinflammatory in the gastrointestinal tract is not known. We have previously shown that male CD-1 mice given a single administration of 0.5% OM develop a severe colitis that is maximum at day 3 and that gradually lessens until essentially absent by day 14. OM-induced neuronal stimulation is reported to be reduced by cannabinoid agonists, and cannabinoid receptor 1 (CB1R)-/- mice have exacerbated experimental colitis. Therefore, we examined the role of cannabinoids in this OM-induced 3-day model of colitis in CD-1 mice and in a 7-day dextran sulfate sodium (DSS) colitis model in BALB/c mice. In OM colitis, the CB1R-selective agonist ACEA and the CB2R-selective agonist JWH-133 reduced (P < 0.05) colon weight gain (means +/- SE; 82 +/- 13% and 47 +/- 15% inhibition, respectively), colon shrinkage (98 +/- 24% and 42 +/- 12%, respectively), colon inflammatory damage score (49 +/- 11% and 40 +/- 12%, respectively), and diarrhea (58 +/- 12% and 43 +/- 11%, respectively). Histological damage was similarly reduced by these treatments. Likewise, CBR agonists attenuated DSS colitis, albeit at higher doses; ACEA at 10 mg/kg, twice daily, inhibited (P < 0.05) macroscopic and microscopic scores (46 +/- 9% and 63 +/- 7%, respectively); whereas 20 mg/kg, twice daily, of JWH-133 was required to diminish (P < 0.05) macroscopic and microscopic scores (29 +/- 7% and 43 +/- 5%, respectively). CB1R and CB2R immunostaining of colon sections revealed that CB1R in enteric neurons was more intense in colitic vs. control mice; however, CB1R was also increased in the endothelial layer in OM colitis only. CB2R immunostaining was more marked in infiltrated immune cells in OM colitis. These findings validate the OM colitis model with respect to the DSS model and provide strong support to the emerging idea that cannabinoid receptor activation mediates protective mechanisms in experimental colitis. The demonstration of CB1R agonist effects in colitis support the neurogenic nature of the OM-induced colitis model and reinforce the importance of neuronal activation in intestinal inflammation.

Animals↗

PubMedDate not supplied

Perinuclear antineutrophil cytoplasmic antibodies in collagenous or lymphocytic colitis with or without celiac disease.

Microscopic forms of colitis, including lymphocytic and collagenous colitis, have been observed in both those with and without celiac disease. Although perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) occur in most patients with ulcerative colitis, investigations in microscopic, particularly lymphocytic, colitis are still needed. In this study atypical p-ANCA was evaluated in 55 patients, including 27 with celiac disease alone, 13 with celiac disease and concomitant lymphocytic colitis, and 15 with microscopic forms of colitis, including lymphocytic and collagenous colitis. Nine patients (16.3%) had atypical p-ANCA, including six with celiac disease and three with a microscopic form of colitis alone. Although five of the six positive celiac disease patients had lymphocytic colitis, all three celiac disease patients with associated primary sclerosing cholangitis--a separate risk factor for a positive assay result--were serologically positive for atypical p-ANCA. These results indicate for the first time that this serological marker may occur in histologically defined celiac disease with or without concomitant lymphocytic colitis. Furthermore, these results suggest that the pathogenesis of ulcerative colitis differs from that of lymphocytic colitis and further emphasizes the heterogeneous nature of these newly recognized types of colonic inflammatory mucosal disorders.

Adolescent↗

PubMed2003

Adoptive transfer of ex vivo immune-programmed NKT lymphocytes alleviates immune-mediated colitis.

T lymphocyte-expressing natural killer (NK) cell markers (NKT cells) play a role in immune regulation. Our aim was to evaluate the in vivo effect of adoptive transfer of immune-programmed NKT cells. Colitis was induced in C57/B6 mice by 2,4,6-trinitrobenzenesulfonic acid. NKT, CD4, CD8 lymphocytes, and dendritic cells (DC) were prepared from spleens of naive mice, animals with colitis, and animals with colitis that were orally tolerized. Subsets of splenocytes, NKT, CD4, and CD8 and NKT+CD4, NKT+CD8, and NKT+DC lymphocytes were prepared. Assessment of the T helper cell type 1 (Th1)/Th2 cytokine secretion paradigm in vitro was performed before and following exposure to the antigen. Adoptive transfer of ex vivo immune-programmed lymphocytes from each group was performed into recipient mice, followed by colitis induction. Ex vivo exposure of NKT cells harvested from mice with colitis-to-colitis proteins [colitis-extracted proteins (CEP)] led to a Th2 cytokine shift. The interleukin (IL)-4/interferon-gamma (IFN-gamma) ratio increased for NKT harvested from colitis-harboring mice following exposure to CEP. Adoptive transfer of NKT lymphocytes harvested from colitis-harboring mice, which were ex vivo-educated, significantly alleviated experimental colitis in vivo. Intrahepatic NKT lymphocytes increased significantly in mice transplanted with NKT lymphocytes harvested from colitis-harboring donor mice, which were ex vivo-exposed to CEP, similar to mice transplanted with NKT lymphocytes harvested from tolerized donors. Exposure of NKT cells to the disease-target antigen induced a significant increase in the IL-4/IFN-gamma cytokine ratio. Adoptive transfer of a relatively small number of immune-programmed NKT cells induced a systemic Th1 to Th2-immune shift and alleviated immune-mediated colitis.

Adoptive Transfer↗

PubMed1997

Nicotine: does it have a role in the treatment of ulcerative colitis?

OBJECTIVES: To review the epidemiology, pathophysiology, diagnosis, clinical manifestations, and treatment of ulcerative colitis, with emphasis on the relationship between smoking, nicotine, and ulcerative colitis, and the most recent clinical trials on the use of nicotine in the treatment of ulcerative colitis. DATA SOURCES: A MEDLINE search (1966 to present) of English language literature regarding the use of various nicotine dosage forms in the treatment of ulcerative colitis. Additional literature was obtained from bibliographic literature searches of appropriate articles identified through this search. DATA SELECTION: All appropriate journal articles focusing on ulcerative colitis and current treatment options, with emphasis on clinical trials involving the use of nicotine, were considered by the authors for inclusion. DATA SYNTHESIS: Ulcerative colitis is a chronic inflammatory disease state of unknown etiology. Its progression is erratic, with patients experiencing periods of exacerbations and remissions. Current therapeutic options have yielded less than satisfactory results. With the discovery of the potential relationship between nonsmoking status and the onset of ulcerative colitis and the development of various nicotine dosage forms came the hypothesis that nicotine may play a protective role against the development of ulcerative colitis and maintenance of remission. Hence, investigators began conducting clinical trials on the use of available nicotine dosage forms in the management of ulcerative colitis. The most recent clinical trials on the use of nicotine in the management of ulcerative colitis have suggested that nicotine, in combination with conventional pharmacologic therapy, may result in clinical improvement in some patients. The use of nicotine as a single agent cannot be recommended at this time. Clinical trials have also revealed poor patient tolerability and long-term compliance due to nicotine's significant adverse effect profile. Overall, investigation of nicotine in the treatment of ulcerative colitis has yielded disappointing results. CONCLUSION: Nicotine cannot be recommended as adjunctive or single therapy for the treatment of ulcerative colitis and will not alter current treatment options. Further research in this area is necessary with focus on enhancing understanding of disease pathophysiology, therapeutic effects of nicotine, and reducing nicotine's adverse effect profile.

Clinical Trials as Topic↗

PubMed1991

A prospective evaluation of diversion colitis.

Numerous case reports suggest that diversion of the fecal stream results in nonspecific colitis, with abnormalities ranging from minimal friability to gross ulceration. Published reports consist largely of patients with symptomatic colitis, and there are scant data suggesting at what frequency diversion colitis actually occurs. In an attempt to identify the frequency of diversion colitis and any associated etiologic factors, 20 patients scheduled for colostomy closure at Grady Memorial Hospital between 8/1/88 and 6/15/89 underwent colonoscopy, including the excluded segment, to evaluate for diversion colitis. Colostomies were performed for the management of diverticulitis, trauma, cancer, protection of an anastomosis, and diversion of fecal fistula. Patients with ulcerative colitis or Crohn's disease were excluded. The colon was classified grossly as normal or colitis (including easy friability, edema, inflammation, and ulceration as colitis). Fourteen of the 20 patients (70%) had findings of diversion colitis (DC), while six had a normal exam (NL). Nine biopsies were performed in the DC group and all revealed microscopic abnormalities. One of the normal patients was also biopsied, revealing mild, nonspecific changes. There was no difference in mean age (DC 49.3, NL 48.2), interval from formation of colostomy (DC 9.21 +/- 7.27 months, NL 2.83 +/- 1.94 months), type of colostomy, or reason for colostomy in the two groups. None of the DC patients had symptoms of colitis (mucous or bloody discharge, tenesmus, or pain), and one of the DC patients manifested symptoms of colitis after colostomy closure. We conclude that diversion colitis is a common subclinical problem in patients with a diverting colostomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

PubMed1991

Phenotypes and spontaneous immunoglobulin production in mononuclear cells suspensions isolated from colonic biopsies of patients with mild active and quiescent ulcerative colitis.

Lamina propria mononuclear cells can be isolated from mucosal specimens of human colon. In the present study, we have explored whether both the phenotypes and functional properties can be studied in lamina propria mononuclear cell suspensions isolated from the same set of endoscopic biopsies in patients with ulcerative colitis. The counts of CD11b+ lamina propria mononuclear cells in mild active ulcerative colitis were significantly higher than those of both quiescent ulcerative colitis and controls. Similarly, the CD16+ and the CD19+ lamina propria mononuclear cells were significantly increased in mild ulcerative colitis patients in comparison to both quiescent ulcerative colitis and control lamina propria mononuclear cells. Lamina propria mononuclear cells from all the biopsy samples appeared to produce detectable amounts of immunoglobulins of the three classes. The production of IgG in mild ulcerative colitis cultures was significantly higher than that observed in quiescent ulcerative colitis and controls. In contrast, the production of IgA in active ulcerative colitis lamina propria mononuclear cell cultures appeared to be significantly lower than that of both quiescent ulcerative colitis and controls. This study shows that morphology, phenotypes, and functional properties can be assessed in lamina propria mononuclear cell suspensions obtained from the same set of endoscopic biopsy samples. We have also shown that changes in phenotypes and functional status of lamina propria mononuclear cells occurred in mild active ulcerative colitis while no significant abnormality of these parameters was found in quiescent ulcerative colitis. This indicates that a normalization of mucosal immune functions occurs in ulcerative colitis patients when complete clinical and histological remission is achieved.

Biopsy↗

PubMed1999

Clostridium difficile colitis after kidney and kidney-pancreas transplantation.

OBJECTIVE: To determine the timing and risk factors involved in the development of Clostridium difficile (CD) colitis in kidney and kidney-pancreas transplant recipients. BACKGROUND DATA: The incidence of CD colitis after kidney and kidney-pancreas transplantation has not been studied in detail. The question of whether the immunosuppressed transplant recipient is more prone to CD colitis and its complications (i.e., megacolon, perforations) and the risk factors involved have not been determined. METHODS: We retrospectively reviewed our experience in kidney and kidney-pancreas recipients who received transplants between January 1, 1985 and December 31, 1994. We divided these recipients into three groups: pediatric kidney recipients, adult kidney recipients, and kidney-pancreas recipients. For each group, we assessed the timing of infection, primary disease, colitis treatment, and any concurrent complications or risk factors. RESULTS: Of 1932 transplants, 159 recipients developed post-transplant CD colitis. 132 charts were available for review. Forty-three pediatric kidney recipients developed CD colitis. Their mean age was 3.2 yr; 74% (n = 37) of them developed their colitis during their initial hospital stay, with the mean timing of infection being 33 d. Forty-one (95%) had undergone intra-abdominal placement of the graft, with renal artery anastomoses to the aorta. Fifty adult kidney recipients developed CD colitis. Thirteen (26%) developed colitis during their initial hospital stay, with the mean timing of infection (for all adult kidney recipients) being 15 months. Thirty-nine kidney-pancreas recipients developed CD colitis. Mean timing of infection was 6 months. The overall incidence of CD colitis was 8%, with 16% in the pediatric kidney group, 15.5% in the kidney-pancreas group, and 3.5% in the adult kidney group. The difference in mean timing of infection was significant between the three groups (p < 0.001 for pediatric versus adult kidney recipients, p = 0.002 for pediatric kidney versus kidney-pancreas recipients, and p = 0.2846 for adult kidney versus kidney-pancreas recipients). CONCLUSION: The incidence of CD colitis is increased in pediatric kidney and kidney-pancreas recipients. Young recipient age ( < 5 yr), female gender, treatment of rejection with monoclonal antibodies, antibiotic use, and intra-abdominal graft placement have been shown to increase the incidence of this disease. Further studies concerning prevention in the high-risk groups are needed.

Adolescent↗

PubMed1996

Prognostic criteria in Clostridium difficile colitis.

OBJECTIVE: To determine the prognostic factors in Clostridium difficile (CD) colitis. METHODS: We conducted a retrospective study of proven cases of CD colitis in l8 months. Seventy six patients (from a 605-bed community hospital in the Bronx, NY) with proven CD colitis were studied. Mortality in patients with CD colitis was also examined. RESULTS: Seventy six patients with proven CD colitis were admitted between January 1993 and June 1994. Eighteen patients died during the same admission. Upon admission, serum albumin was less than 25 g/L in 12 (20.6%) of the survivors and in eight (44%) of the deceased patients (p <0.05). A fall in serum albumin levels was noted with the onset of symptoms of CD colitis in those who survived as well as in those who died, with a greater fall of 11.2 g/L (range 10-20 g/L) in patients who died compared with a fall of 6 g/L (range 5-10 g/L)in those who survived (p <0.05). Use of more than three antibiotics was noted in 13 (72%) of those who died and in 18 (31%) of those who survived (p <0.05). Persistence of CD cytotoxin 7 or more days after initiation of treatment was present in 14 (77%) of those who died and in eight (13%) of the survivors (p <0.01). Duration of hospitalization correlated with the development of CD colitis (35.89 vs 11.7 days) with no significant difference between survivors and deceased patients with CD colitis. Factors such as age, sex, residence, past medical history score, mean score of presenting complaints of CD colitis, history of prior episodes CD colitis, and mean number of recurrent episodes showed no difference in mortality. CONCLUSION: Factors predictive of an increased mortality in patients with CD colitis include a serum albumin of less than 25 g/L on admission, a fall in serum albumin level of greater than 11 g/L at the onset of symptoms of CD colitis, use of three or more antibiotics, and persistence of positive CD cytotoxin in the stool after completion of 7 or more days of treatment.

Adult↗

PubMed1991

Anti-neutrophil cytoplasmic antibodies in ulcerative colitis. Comparison with other colitides/diarrheal illnesses.

Previous studies from this laboratory showed that serum anti-neutrophil cytoplasmic antibodies, distinct from those associated with active Wegener's granulomatosis, are present in the majority of patients with ulcerative colitis. In this study, the specificity of anti-neutrophil cytoplasmic antibodies for ulcerative colitis as compared with other colitides and diarrheal illness was determined. In a blinded study, test samples of serum were screened for anti-neutrophil immunoglobulin G in a fixed neutrophil enzyme-linked immunosorbent assay. Levels of neutrophil binding by immunoglobulin G and titers of anti-neutrophil immunoglobulin G in sera from patients with ulcerative colitis and patients with ulcerative colitis post colectomy were each significantly greater than the levels and titers for normal controls and patients with a variety of other colitides and diarrheal illnesses. Levels of neutrophil binding for colonic Crohn's disease, bacterial/amoebic colitis, the irritable bowel syndrome with diarrhea, and other miscellaneous diarrheal illnesses were not significantly different than the levels for normal controls. Although the levels of binding for collagenous colitis were significantly less than the levels for ulcerative colitis, they were significantly greater than the levels for normal controls. Patterns of neutrophil binding by serum samples that were positive in the enzyme-linked immunosorbent assay were determined by indirect immunofluorescence. Perinuclear staining was the predominant pattern shown by sera from patients with ulcerative colitis. The combination of a positive value in the enzyme-linked immunosorbent assay and a perinuclear immunofluorescence pattern was 60% sensitive and 94% specific for ulcerative colitis. It is concluded that anti-neutrophil cytoplasmic antibodies in ulcerative colitis are not simply an epiphenomenon related to inflammation of the colon. Identification of the antigen(s) to which these autoantibodies are directed may facilitate understanding of the underlying immune response and may allow development of an assay that is more sensitive and specific for ulcerative colitis.

Adult↗

PubMed2001

Flow cytometric and histologic evaluation in a large cohort of patients with ulcerative colitis: correlation with clinical characteristics and impact on surveillance.

PURPOSE: To examine the prevalence of DNA aneuploidy as a function of the extent of ulcerative colitis and to study the correlation of aneuploidy with clinical characteristics. Furthermore, the occurrence of aneuploidy and dysplasia during colonoscopic surveillance was studied in a subset of these patients. METHODS: By analyzing 5404 biopsy samples of 368 patients with ulcerative colitis, we have evaluated the importance of DNA ploidy measured by flow cytometry. We have also investigated the influence of extent (219 patients with extensive or total colitis vs. 149 patients with localized colitis) and duration of colitis on the development of dysplasia (patients with biopsy specimens that showed inflammation alone were compared with those with biopsy specimens that were equivocal or positive for dysplasia) and aneuploidy. Included was a subgroup of patients with ulcerative colitis and primary sclerosing cholangitis (n = 16). RESULTS: Aneuploidy was found in 8.7 percent (32/368) of all patients. The prevalence of aneuploidy increased by the extent of ulcerative colitis (2 percent localized, 6.8 percent extensive colitis, 14.9 percent total colitis). The frequency of aneuploidy was higher in patients with disease duration longer than 10 years (P = 0.007). Patients with ulcerative colitis and primary sclerosing cholangitis were more likely to develop aneuploidy (9/16, 56.3 percent vs. 14/120, 11.7 percent; P < 0.001) and dysplasia (4/16, 25 percent vs. 10/120, 8.3 percent; P = 0.06) than patients without primary sclerosing cholangitis. CONCLUSION: Because DNA aneuploidy represents an early alteration during neoplastic transformation in ulcerative colitis, flow cytometry is a valuable tool in the surveillance of those patients. Primary sclerosing cholangitis represents an additional risk factor for the development of DNA aneuploidy and dysplasia.

Aneuploidy↗

PubMed1998

Mucosal metabolism in ulcerative colitis and Crohn's disease.

PURPOSE: Colonic mucosal metabolism of butyrate may be impaired in ulcerative colitis. In this study we sought to confirm this observation, to determine if a similar change occurs in Crohn's colitis, and to establish whether a panenteric disorder of butyrate metabolism exists in either condition. METHODS: With use of a microculture technique, mucosal metabolic fluxes of 14[C]-labeled butyrate and 14[C]-labeled glutamine were measured as 14[C] carbon dioxide production in mucosal biopsy specimens from the colon and ileum in patients with ulcerative colitis, Crohn's colitis, and healthy bowel. Results were expressed as pmol/microg biopsy DNA/hour. RESULTS: In the colon the mucosal metabolic fluxes of both butyrate and glutamine are reduced in both ulcerative colitis and Crohn's colitis compared with healthy controls. These changes were most marked in the presence of moderate to severe mucosal inflammation, there being no significant difference in mucosal metabolic flux between mildly inflamed mucosa and healthy controls. In the ileum the mucosal metabolic fluxes of butyrate and glutamine did not differ between healthy controls and those with either ulcerative colitis or Crohn's colitis. CONCLUSIONS: Changes in colonic mucosal metabolism of butyrate and glutamine in inflammatory bowel disease occur as a consequence of the inflammatory process and are not peculiar to ulcerative colitis. Ileal mucosal metabolism is unchanged in ulcerative colitis and Crohn's colitis, indicating the absence of a panenteric abnormality of mucosal metabolism in these two conditions.

Biopsy↗

PubMed1998

Cytokine production from colonic T cells in patients with ulcerative colitis with and without primary sclerosing cholangitis.

PURPOSE: Only five percent of all patients with ulcerative colitis develop primary sclerosing cholangitis. T cells accumulate at the sites of the colonic and bile duct inflammation in both ulcerative colitis and primary sclerosing cholangitis. T helper cell populations comprise functionally distinct subsets characterized by the cytokines they produce. Several alterations in cytokine production have been described in patients with ulcerative colitis. The aim of this study was to investigate possible differences in T helper subsets and cytokine production in peripheral blood and colonic mucosa among ulcerative colitis patients with and without primary sclerosing cholangitis. METHODS: Eleven patients with primary sclerosing cholangitis and extensive ulcerative colitis, 11 patients with extensive ulcerative colitis and no liver disease, and 5 patients without any history of liver disease who underwent routine colonoscopy because of previous polypectomy were included in the study. Colonoscopy with multiple biopsies was performed on all patients. Lamina propria mononuclear cells and peripheral blood mononuclear cells were isolated. A modified version of solid-phase enzyme-linked immunospot assay was used for the separate counting of cells producing interferon-gamma, interleukin-2 (T helper 1), and interleukin-4 (T helper 2). RESULTS: No differences in spontaneous production of cytokines from peripheral blood mononuclear cells was found among the three groups. Patients with primary sclerosing cholangitis compared with patients with ulcerative colitis without liver disease showed a significant increase in the number of cells secreting interferon-gamma after purified protein derivative stimulation (P < 0.02). More cells secreting interferon-gamma were found in the two ulcerative colitis groups than in the cell populations from healthy controls (P < 0.03). The number of cells secreting interferon-gamma in the primary sclerosing cholangitis group was significantly lower than in the ulcerative colitis group without liver disease (P < 0.04). The number of cells secreting interleukin-4 was lower in the primary sclerosing cholangitis group than among the patients with ulcerative colitis only (P = 0.05). CONCLUSION: Isolated lymphocytes from colonic mucosa differ in cytokine production in patients with ulcerative colitis with and without primary sclerosing cholangitis.

Cholangitis, Sclerosing↗

PubMed2001

Antibodies to neutrophil cytoplasma in patients with ulcerative colitis and their first-degree relatives in Thailand.

BACKGROUND: The prevalence of perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) does not significantly vary in ethnically diverse populations. The prevalence of p-ANCA is high in ulcerative colitis and primary sclerosing cholangitis. While the prevalence of ulcerative colitis in Asian populations is low, it is interesting to know the prevalence of p-ANCA in such a population. METHODS: Sera from 33 cases of ulcerative colitis diagnosed during the last 10 years at the diarrhea clinic, Division of Gastroenterology, Siriraj Hospital, were prospectively compared with case controls consisting of 15 cases of diarrhea from non-inflammatory bowel diseases and 25 non-diarrheic patients. Indirect immunofluorescence assay was used to detect p-ANCA in all the sera. RESULTS: Positive p-ANCA tests were found in 13 of the 33 patients with ulcerative colitis and in one of the 40 controls. Sensitivity of the test was 39.4% and the specificity was 97.5%. The one patient with positive p-ANCA in the control group was the patient with irritable bowel syndrome. Of the 13 p-ANCA-positive ulcerative colitis patients, two cases were found to have proctosigmoiditis, seven cases had left-sided colitis, and four cases had pancolitis. Perinuclear antineutrophil cytoplasmic antibodies was one of the 22 cases of first-degree relatives of ulcerative colitis patients (22 relatives from 12 index ulcerative colitis cases). There was no correlation between the positivity of p-ANCA and disease activity, and extent of the disease. CONCLUSION: The prevalence of p-ANCA in Thai patients with ulcerative colitis (39.4%) is lower than that in the Western population. Although the prevalence of p-ANCA is low in the Thai population, it should serve as a useful tool in diagnosing ulcerative colitis in this part of the world where the disease is uncommon and difficult to diagnose. The negativity of p-ANCA in almost all first-degree relatives of Thai ulcerative colitis patients should be further elucidated.

Adult↗

PubMed2002

Fusobacterium varium localized in the colonic mucosa of patients with ulcerative colitis stimulates species-specific antibody.

BACKGROUND: Microbial agents are a possible cause of ulcerative colitis. We have previously reported evidence of bacteria invading the colonic mucosa of patients with ulcerative colitis. We have isolated bacteria from inflamed colonic mucosa, examined the localization of the species in the mucosa, and assayed for serum antibodies to the bacteria. METHODS: Cohorts of 31 per group were enrolled from patients with active ulcerative colitis, Crohn's disease, ischemic colitis, and colon adenomas. A group of 31 healthy controls were also studied. The presence of bacteria in biopsies of patients with ulcerative colitis was analyzed by both isolation and immunohistochemistry. Sera from patients were tested for bacterial antibodies using both Western blots and enzyme-linked immunosorbent assay (ELISA). RESULTS: Only sera from patients with ulcerative colitis gave specific reactions with Fusobacterium varium in Western blot assays. The detection rate of specific bands was higher for patients with ulcerative colitis (61%) than for subjects with either Crohn's disease (13%) or healthy controls (29%) (P < 0.001 and P = 0.021, respectively). The ELISA showed that the mean optical densities with extracts of F. varium as antigen were significantly higher for ulcerative colitis patients than for subjects with either Crohn's disease or healthy controls (P < 0.001). Immunohistochemical detection of F. varium in colonic mucosa was significantly higher in patients with ulcerative colitis (84%) than for subjects with either Crohn's disease (16%) or other controls (3-13%) (P < 0.001). CONCLUSIONS: Fusobacterium varium bacteria were present in a significant number of patients with active ulcerative colitis, and should be tested in therapeutic trials in order to confirm the causal relationship between F. varium and ulcerative colitis.

Adolescent↗

PubMed1996

Butyrate enemas in experimental colitis and protection against large bowel cancer in a rat model.

BACKGROUND & AIMS: Butyrate is effective in experimental colitis by increasing transglutaminase activity. Because ulcerative colitis increases the risk of colonic neoplasia, the aim of this study was to investigate whether butyrate treatment reduces mucosal sensitivity to colon cancer development in rats with experimental colitis. METHODS: Colon cancer was induced by azoxymethane injections in 10 rats with trinitrobenzensulfonic acid-induced colitis and 10 rats without colitis. Three additional groups of rats with colitis were treated with butyrate, mesalamine, and saline enemas, respectively, twice daily for 8 weeks; 1 week after colitis induction, tumors were induced. Biopsy specimens for assessment of proliferation pattern and transglutaminase activity were obtained during the latent period of cancer development. Characteristics of tumors were recorded 27 weeks after the first exposure to azoxymethane. RESULTS: Experimental colitis enhanced carcinogenesis; butyrate therapy reduced both incidence and size of tumors and also affected colonic proliferation pattern. Transglutaminase levels were restored by butyrate treatment in rats with colitis. CONCLUSIONS: The protective effect of butyrate against large bowel cancer in experimental colitis suggests its usefulness in long-term therapy to decrease disease relapses and to reduce colon cancer risk in ulcerative colitis.

Animals↗

PubMed2003

The clinical significance of focal active colitis in pediatric patients.

The clinical significance of focal neutrophilic infiltrates in crypt epithelium in colorectal biopsies or focal active colitis has been studied in adult populations, but little is known about this entity in children. The incidence of Crohn's disease in adult patients presenting with focal active colitis has varied between 0% and 13% in previous studies, whereas the incidence of infectious-type colitis has been reported to be nearly 50%. We reviewed 31 cases of focal active colitis diagnosed in pediatric patients without a history of inflammatory bowel disease between 1989 and 2000. Pathologic variables studied included number and location of inflamed crypts and distribution and character of lamina propria inflammation. Clinical follow-up was obtained from patient charts. Two patients were lost to follow-up. Follow-up on the remaining 29 patients ranged from 4 months to 7 years with a mean of 4.2 years. Eight patients (27.6%) developed Crohn's disease. Nine patients (31%) appeared to have acute infectious-type colitis, one with C. difficile. Eight patients (27.6%) had focal active colitis, which did not correlate with their symptoms or ultimate clinical diagnosis. These were termed idiopathic focal active colitis. Two patients were found to have allergic colitis, one had ulcerative colitis, and one had Hirschsprung's disease. Pediatric patients with focal active colitis have a much higher incidence of Crohn's disease than adults with same entity. Hence, it is important to document the presence of focal active colitis in pediatric patients.

Adolescent↗

PubMed2001

Celiac disease is highly prevalent in lymphocytic colitis.

A high frequency of celiac disease is reported in patients with collagenous colitis. Limited information is available on the frequency of celiac disease in lymphocytic colitis. The aim of our study was to determine the prevalence of celiac disease in microscopic colitis (collagenous and lymphocytic colitis). Patients were identified from a pathology registry of microscopic colitis from 1987 to 1999. Pathology reports and medical records were reviewed for previous small bowel biopsies and/or celiac serology. We identified 113 patients with microscopic colitis, and 46 patients underwent a small bowel biopsy and/or celiac serology. Of these, 27 patients had lymphocytic colitis (63% female; age, 58.6 +/- 16.2 years) and 19 patients had collagenous colitis (79% female; age, 61.8 +/- 13.6 years). Small bowel biopsy alone was performed in 28 of 46 patients, celiac serology alone was performed in 10, and both small bowel biopsy and celiac serology were performed in 8. Celiac disease was identified in 4 patients by small bowel histology; all had lymphocytic colitis (4 of 27 patients, 15%). This frequency of celiac disease is significantly higher than the highest reported U.S. prevalence of celiac disease (4/1,000 individuals; p < 0.01). There is a high frequency of celiac disease in patients with lymphocytic colitis. Given the importance of the early detection of celiac disease, it should be excluded in all patients with lymphocytic colitis, particularly if diarrhea does not respond to conventional treatment.

Celiac Disease↗