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Role of gamma delta T cells in the inflammatory response of experimental colitis mice.

We examined the severity of experimental colitis induced by dextran sulfate sodium (DSS) using immunologically manipulated mice. C57BL/6 mice showed more severe colitis than BALB/c mice, but mice of both strains recovered fully from the disease after the removal of DSS from their drinking water. The infiltrated cells at the lesions were mainly granulocytes in normal littermates. However, C.B-17 scid, IL-7Ralpha deficient, and TCR-Cbetadelta double-deficient mice showed severe colitis and did not recover from the disease even after the removal of DSS. It was found that the infiltrated cells at the lesions in the lethal strains were monocytes. Although both TCR-Cdelta(-/-) and TCR-Cbeta(-/-) mice showed severe colitis phenotypes, infiltration in the former is monocyte-dominant while that in the latter is granulocyte-dominant. Thus the type of cells that infiltrate at the lesions of DSS-induced experimental colitis may be controlled by functional T cell subsets. Immunohistological and RT-PCR analyses of the inflamed colon revealed that the murine homologue of human GROalpha released by some cells under the control of gammadeltaT cells is a possible candidate determining the severity of DSS-induced experimental colitis.

Animals↗

Microscopic colitis.

Microscopic colitis has 2 main subtypes, collagenous colitis and lymphocytic colitis, that are similar clinically and histologically and are distinguished mainly by the presence or absence of a thickened subepithelial collagen band. Microscopic colitis accounts for approximately 10% of chronic watery diarrhea and may be associated with abdominal pain and mild weight loss. It is typically diagnosed in the sixth to eighth decade of life, and there is a female pre-dominance that is more striking for collagenous colitis than for lymphocytic colitis. Endoscopic and radiographic findings of the colon appear normal. Diagnosis is made by colonic biopsy, which shows an intraepithelial lymphocytosis and a mixed inflammatory infiltrate in the lamina propria. Many potential treatments have been reported, but few have been subjected to controlled treatment trials. A stepwise approach to therapy often leads to satisfactory control of symptoms.

Anti-Inflammatory Agents↗

Chronic colitis associated with human immunodeficiency virus infection.

OBJECTIVE: A clinical and pathological description of chronic colitis associated with human immunodeficiency virus (HIV) infection. DESIGN: A retrospective case review. SETTING: Tertiary referral institution and specialist gastroenterology practice. PATIENTS: A series of six patients with human immunodeficiency virus infection and chronic colitis observed for up to four years. RESULTS: The six patients had chronic diarrhoea for longer than six months, rectal bleeding, abdominal pain and stool leukocytosis. The mucosal pattern on colonoscopy showed diffuse proctocolitis, consisting of contact bleeding, superficial ulcerations, exudates, and/or loss of vascular pattern. Colonic biopsies showed a persisting diffuse colitis characterised principally by a mixed inflammatory cell infiltrate (mononuclear cells and neutrophils) and essentially preserved crypt architecture after six to 39 months of histological follow-up. The histopathology over this time frame was not typical of ulcerative colitis or Crohn's disease, nor of the conventionally described forms of infective colitis. HIV nucleic acid was identified by insitu hybridisation in colonic biopsies from four patients. In two of three patients tested, the presence of HIV DNA was confirmed by Southern blot analysis. No other microbial agent could be demonstrated as the cause of diarrhoea. At presentation all patients had CD4+ lymphocyte counts greater than 265 x 10(6)/L and none had the acquired immunodeficiency syndrome. Four patients have gone into remission, the other two patients were not in remission at four and a half to five years after onset. CONCLUSION: We suggest that chronic colitis may represent a new entity related to infection of the colon with human immunodeficiency virus.

Acquired Immunodeficiency Syndrome↗

[Pathophysiology and diagnosis of ischemic colitis].

Ischemic colitis is the most common manifestation of gastrointestinal ischemia. The presumed etiologies are numerous; however, it typically develops spontaneously. It is classified into the transient type, stricture type, and gangrenous type. The majority of patients with ischemic colitis, excluding the gangrenous type, follow a benign clinical course in the absence of major vasculature occlusion. It usually presents as an acute abdominal illness with bloody diarrhea. Diagnosis is confirmed by colonoscopy and/or barium enema. Nongangrenous ischemic colitis usually requires only conservative therapy, including repeated careful assessment, pain control, and fluid replacement, and is associated with a good prognosis. It may lead to the sequela of persistent segmental colitis or colonic strictures, occasionally requiring surgery. Urgent surgery and high morbidity and mortality rates are hallmarks of the gangrenous type. Special consideration must be given to those patients in whom ischemic colitis develops in the context of colon cancer or obstructive colonic lesions. Successful management of a patient with ischemic colitis requires a high degree of clinical suspicion, early diagnosis, careful follow-up, and prompt recognition of persistent disease.

Colitis, Ischemic↗

[Ticlopidine-induced lymphocytic colitis].

Lymphocytic colitis is a clinico-pathological syndrome characterized by chronic diarrhea, normal endoscopy, diffuse colonic mucosal inflammatory changes. Collagenous colitis is defined by a thickening of the collagen plate. The etiology is unknown but immune disorders have been frequently associated with it and it has been linked with the taking of certain drugs such as nonsteroïd anti-inflammatory drugs or veinotonics. We are reporting a case of microscopic colitis associating both lymphocytic and collagenous colitis, wich induced chronic diarrhea in a 65-year-old man. It appeared after he had taken ticlopidine. Diarrhea stopped after he had discontinuated ticlopidine, and recurred after he resumed taking the drug. Histological damages from lymphocytic colitis improved six month after he had stopped taking ticlopidine. Chronic diarrhea induced by ticlopidine might be caused by lymphocytic colitis.

Aged↗

Nutritional therapies for ulcerative colitis: literature review, chart review study, and future research.

Few clinical studies suggest a significant influence of diet or nutritional supplementation on ulcerative colitis. One reason is that ulcerative colitis, like many chronic diseases, is multifactorial. This article will describe and review the relevant literature on ulcerative colitis, including studies of (1) diet and intravenous therapy, (2) nutritional status and nutritional supplementation, and (3) bowel flora and immune function and their influences. Also, results of a retrospective chart review study that was done at a complementary medicine office will be presented. Finally, suggestions for future research will be discussed based on a nutritional model of ulcerative colitis. Taken together, it is hoped that these areas will clarify the current status of ulcerative colitis research and promote the types of investigations that are necessary to establish the validity of nutritional influences on ulcerative colitis as well as the mechanisms that are involved.

Adolescent↗

[Indeterminate colitis (nonspecific inflammatory bowel disease)].

Distinguishing of indeterminate colitis from ulcerative colitis or Crohn's disease in more than 10% of IBD cases as separate diagnostic category (IIBD) is defined by: first, overlapping or paucity of features of two major IBD forms in acute fulminant colitides and few chronic slowly progressive cases without differentiating markers of chronicity, and second, inability to reach specific diagnosis during or after completed clinical, radiological, endoscopical and histopathological examination of chronic colitis with inconclusive presentation of IBD-compatible cases. It implicates the contemporary category of IIBD, until some new relevant data of further clinical (preferably natural history and course of the disease) and histopathological examination of prior biopsies will possibly reclassify 20-75% of these cases into ulcerative colitis category (up to 40%) or Crohn's disease (up to 25%) at a median of 10 years' follow-up. The presence of ileal and/or perianal disease as well as later evident granulomatous and/or fissuring disease, including cases with pouchitis and diversion colitis in addition, could be helpful in favouring of Crohn's disease. Lacking specific signs of disease, IIBD is not a distinct entity. Still, many patients remain in this category. The most far is acute fulminant disease in adolescents and young adults with unusual distribution of transmural inflammation with deep fissuring ulcerations, sometimes of "collar-stud" type and normal mucosa between them, often with relative rectal sparing. There is significant risk of relapse and complications, but mild clinical course and even spontaneous regression are also reported. Failure of ileal pouch-anal anastomosis surgery is about 20% more frequent then in ulcerative colitis with overall worse prognosis in life expectations. Diagnostic problems and the main presentations are discussed in detail, as well as genetic and etiopathogenetic basis for heterogeneity of IBD.

Adult↗

[Generalized intestinal CMV infection with protein-losing syndrome in ulcerative colitis].

Infection by cytomegalovirus (CMV) in immunocompetent patients is rare, and if it occurs it is most often associated with ulcerative colitis. This case illustrates a CMV infection in a patient with an ulcerative colitis combined with CMV-induced protein losing enteropathy, a condition reported in immunocompetent individuals in only a very few cases worldwide. It demonstrates the importance of differentiating between a flare-up of ulcerative colitis and CMV colitis. The indication for antiviral therapy is discussed. A 76-years-old patient with a 23-year history of leftsided ulcerative colitis presented with acute pancolitis sparing the rectum. He showed no evidence of impaired host defence, nor has he ever had taken immunosuppressive drugs. Disseminated primary CMV infection involving of the colon, the oesophagus and the small intestine with protein losing enteropathy was diagnosed on the basis of histology, culture and serology. In view of the long duration of the illness and the highly active infection, antiviral therapy with ganciclovir was given and led to a dramatical improvement of all disease manifestations. The patient subsequently remained in remission from ulcerative colitis for three years.

Aged↗

Carcinoma and epithelial dysplasia complicating ulcerative colitis.

The pathology of 19 specimens of carcinoma complicating ulcerative colitis, resected in the University Department of Surgery of the General Infirmary at Leeds, was reviewed with particular reference to the incidence of epithelial dysplasia. The carcinomas were found to be more frequently multiple, more evenly distributed in the large bowel, and much more often of atypical macroscopic appearances and of mucoid histological type than ordinary colorectal carcinomas, but the proportion of poorly differentiated tumours complicating ulcerative colitis was not as high as previously reported. Of the patients in our series 26% are alive and well at least 5 years after surgery. Unequivocal epithelial dysplasia was demonstrated in some part of the large intestine in 15 of 19 specimens with colitis carcinoma, but was also found in 4 of 14 specimens from a "control" series of patients with longstanding total colitis but without carcinoma. Clearly, therefore, the finding of dysplasia in a rectal biopsy of a patient with colitis is not a reliable guide to the presence of a frank carcinoma elsewhere in the bowel. Whether it indicates a special predisposition to the development of a growth in the future, as might be postulated from the analogy of similar changes in other organs, cannot be determined on the data of this study. The fact that epithelial dysplasia when present in colitis is often patchy in distribution and frequently spares the rectum even in patients with definite carcinomas makes a negative rectal biopsy particularly unreliable in deciding on the absence of a tumour or the lack of predisposition to it. Multiple biopsies from different parts of the colon as well as the rectum would thus seem to be desirable if mucosal sampling is to be employed as a screening test.

Adult↗

Obliterative arteritis with nitric oxide synthase and HLA-DR expression in Crohn's colitis.

BACKGROUND/AIMS: To cast light on whether inflammatory vascular injury is a possible pathogenic mechanism in Crohn's disease, the histological characteristics of vascular lesions were investigated. METHODOLOGY: Affected vessels in surgically resected colons from 23 patients with Crohn's disease, 20 with ulcerative colitis, 7 with ischemic colitis, and 9 normal controls were analyzed by Victoria blue and hematoxylin and eosin staining as well as immunohistochemistry for HLA-DR, nitric oxid synthase, vascular endothelial growth factor and E-cadherin. RESULTS: Inflammatory-cell infiltrates affecting arteries, accompanied by obliterative intimal thickening, were more frequent in Crohn's disease cases than in the other groups (P < 0.05-0.0001). Crohn's disease activity was positively correlated with the degree of obliterative arteritis. Granulomatous vasculitis was found exclusively in Crohn's disease (10 cases; 43.5%). In addition, focally enhanced endothelial staining of HLA-DR, with expression in granulomas adjacent to vessels was occasionally observed. In the endothelium of affected vessels, strong expression of HLA-DR was more prevalent in Crohn's disease and/or ulcerative colitis as compared with the ischemic colitis and controls (P < 0.05-0.01). In the involved arteries, enhanced endothelial nitric oxide synthase expression was most common in Crohn's disease among the groups (P < 0.05). A few cases of Crohn's disease, ulcerative colitis and ischemic colitis were positive for inducible nitric oxide synthase, vascular endothelial growth factor or E-cadherin in the vessel walls. CONCLUSIONS: The presence of characteristic obliterative arteritis and granulomatous vasculitis, a possible cause of ischemic injury, supports, in part, a vascular hypothesis for the pathogenesis of Crohn's disease. Enhanced expression of endothelial nitric oxide synthase and HLA-DR possibly reflects compensatory endothelium-mediated vasodilation and amplification of the immune response, respectively.

Adult↗

[Evolution and treatment response in microscopic colitis].

AIM: To study the clinical characteristics, treatment response and evolution in patients with microscopic colitis. MATERIAL AND METHODS: We performed a retrospective analysis of 24 patients (15 with collagenous colitis and 9 with lymphocytic colitis). Clinical and diagnostic features, treatment response and evolution according to the presence of maintenance therapy were evaluated. RESULTS: The mean age of the patients was 59.7 years and most were male. Nine patients took non-steroidal anti-inflammatory drugs (NSAID). No significant association was found with other drugs. Four patients presented associated rheumatological disease. Most patients presented insidious-onset diarrhea without pathological products, which was frequently associated with other symptoms (abdominal pain, bloating, weight loss, asthenia, tenesmus, and incontinence). Seven patients showed a slight increase in globular sedimentation rate. Fat in stools and radiological investigations (transit and opaque enema) were normal in patients who underwent these tests. Endoscopy revealed non-specific alterations in 42% of the patients while results were normal in the remaining patients. One patient showed clinical improvement on withdrawal of NSAIDs and 4 patients improved spontaneously. Clinical response was achieved in 7 of 13 patients treated with antimotility drugs, in 8 of 9 patients treated with salicylates, in 3 treated with oral corticoids, in 1 treated with cholestyramine and in 1 treated with topical budesonide. Nineteen patients required no maintenance therapy, 4 were administered salicylates and 1 was administered cholestyramine. After a mean follow-up of 42 months, evolution was chronic and intermittent in 14 patients and chronic and continuous in 1; 9 patients presented a single episode. No significant differences were found between patients administered maintenance therapy and those who were not or between collagenous colitis and lymphocytic colitis in the parameters analyzed. CONCLUSIONS: Microscopic colitis constitutes a group of diseases characterized by chronic diarrhea, few systemic effects and minimal radiological and/or endoscopic alterations. Evolution is characterized by recurrent episodes, with good response to treatment with cholestyramine, salicylates or corticoids when required.

Adult↗

[Colonic malacoplakia and ulcerative colitis: report of a case].

Malacoplakia is a form of chronic granulomatous inflammatory reaction that rarely affects the digestive tract and has exceptionally been reported in association with ulcerative colitis. We report a new case in a 58-year-old woman suffering from ulcerative colitis. As colitis worsened, the patient received systemic steroid therapy but symptoms did not improve. As colonic perforation was suspected, a sub-total colectomy was performed. Histopathological study revealed a diffuse infiltration of the colonic mucosa by sheets of large macrophages with eosinophilic granular cytoplasm and characteristic cytoplasmic inclusions (Michaelis-Gutmann bodies) together with active and chronic lesions of ulcerative colitis. Malacoplakia gradually disappeared under antibiotics and did not recur whereas ulcerative colitis remained active. In our case, as in three similar published cases associated with ulcerative colitis or Crohn's disease, malacoplakia was probably triggered by steroid therapy and was not clinically suspected. This particular and potentially severe inflammation must be recognized and treated in order to prevent worsening of the associated bowel disease.

Adrenal Cortex Hormones↗

Doppler US of superior mesenteric artery in the assessment of ulcerative colitis. A prospective study.

BACKGROUND/AIMS: The purpose of this study was to correlate blood flow velocity in the superior mesenteric artery and activity of ulcerative colitis. METHODOLOGY: Doppler spectral analysis of superior mesenteric artery blood flow velocities were obtained in a blind study from 28 patients after fasting (A1: 13 patients with pancolitis, A2: 5 patients with subtotal colitis, B: 10 patients with left-sided colitis) and 50 healthy volunteers (control group). Disease activity was determined with clinical and endoscopic findings. RESULTS: A significant increase in superior mesenteric artery blood flow measurements was observed in the active pancolitis group A1 [Vsyst = 3.64 +/- 0.18 m/sec and Vdiast = 0.94 +/- 0.09 m/sec as compared with healthy volunteers (Vsyst = 1.14 +/- 0.07 m/sec, Vdiast = 0.38 +/- 0.04 m/sec) P < 0.01. A minor increase in superior mesenteric artery blood flow velocity was observed in patients with subtotal colitis, group A2 (Vsyst = 2.06 +/- 0.14 m/sec, Vdiast = 0.45 +/- 0.05 m/sec) as compared with healthy volunteers P < 0.01. In group B with left sided colitis superior mesenteric artery velocity changes were not statistically significant (P > 0.05). CONCLUSIONS: Doppler US velocity measurement of superior mesenteric artery may be used as an adjunct in the assessment of ulcerative colitis extension and activity.

Adult↗

Three cases of primary sclerosing cholangitis associated with ulcerative colitis; diagnostic usefulness of magnetic resonance cholangiopancreatography.

BACKGROUND/AIMS: Primary sclerosing cholangitis is often accompanied by inflammatory bowel disease in western countries. However, the incidence of primary sclerosing cholangitis in patients with ulcerative colitis appears to be much lower in Japan. METHODOLOGY: Between 1980 and 1998, a total of 402 patients with ulcerative colitis were seen in our department. The patients were evaluated by abdominal ultrasonography, endoscopic retrograde cholangiopancreatography, and/or magnetic resonance cholangiopancreatography when persisting abnormalities of biochemical findings suggested the presence of hepatobiliary diseases. RESULTS: Of the 402 patients with ulcerative colitis, 3 patients with primary sclerosing cholangitis were found. There were 2 men and 1 woman. One patient had left-sided colitis while 2 had total colitis. Magnetic resonance cholangiopancreatography was done in 2 of these 3 patients and demonstrated diagnostic features of primary sclerosing cholangitis. All 3 patients had intra- and extrahepatic involvement by primary sclerosing cholangitis. One male patient died due to progressive hepatic failure. The other male patient was treated with ursodeoxycholic acid, but serum alkaline phosphatase level remained above the normal range. The female patient maintained normal serum alkaline phosphatase levels without specific medication. CONCLUSIONS: Magnetic resonance cholangiopancreatography is the most safe and convincing tool for the diagnosis of coexistent primary sclerosing cholangitis in the patients with ulcerative colitis.

Adult↗

[Zinc acts as a protective agent on the mucosal barrier in experimental TNBS colitis].

The aim of this study was to analyze the effect of enterally given zinc on the impaired epithelial barrier function in experimental TNBS colitis in rats. Rats in therapy group were zinc-fed in therapeutic dose. 48 hours after induction of TNBS colitis the rats were killed, the distal colon was resected and mounted into an Ussing chamber. The following electrophysiological measurements were carried out: 1. Flux measurements for Na+ and mannitol as a parameter of paracellular permeability, 2. Resistance measurements of the colon, distinguishing between pure epithelial resistance and resistance of the subepithelial tissue. In TNBS colitis we found a marked increase of both fluxes as a parameter of enhanced paracellular permeability (factor 3). Further there was a drastic reduction of total resistance, and especially of pure epithelial resistance indicating a massive epithelial barrier defect. In rats treated by zinc the increase of paracellular permeability was increased only by a factor of 2, and there was only a moderate decrease of resistance. For the first time we demonstrated zinc to have a protective effect on damaged mucosal barrier function in TNBS colitis. These results confirm the data collected in guinea pigs with malnutrition, whose intestinal integrity could be improved by zinc. Further studies are necessary in order to test whether this protective effect of zinc on mucosa barrier in experimental colitis may be relevant also in human ulcerative colitis.

Administration, Oral↗

[DNA ploidy and dysplasia in ulcerative colitis--interim analysis of a prospective study].

DNA ploidy and cell cycle phases were evaluated by flow cytometry in colonic biopsy specimens from 107 patients with ulcerative colitis in order to analyse the prevalence of DNA aneuploidy as an indicator of numerical chromosomal aberrations and the cell proliferation in all forms of ulcerative colitis. Whereas G2/M-phase fractions in ulcerative colitis and in controls were comparable (2.7 +/- 1.1% vs. 2.8 +/- 1.1%), S-phase fractions in ulcerative colitis exceeded those of controls (7.5 +/- 3.2% vs. 6.5 +/- 2.3%; p < 0.01). In 28 control patients, only diploid DNA histograms existed. Single or multiple aneuploid stem lines were detected in 10 patients with ulcerative colitis (9.3%). Aneuploidy was nearly exclusively associated with pancolitis. Dysplasia was present in 13 patients (indefinite: 8; low-grade: 5), of whom 5 patients also showed DNA aneuploidy. 5 patients with non-dysplastic mucosa exhibited DNA aneuploidy. Because dysplasia and DNA aneuploidy can be discordant and might therefore identify different subgroups at risk, flow cytometry might play a role as a valuable complement to histological examination in surveillance programs of ulcerative colitis.

Adult↗

[Effects of tanguticum maxim polysaccharide on ulcerative colitis induced by TNBS in rats].

OBJECTIVE: To evaluate the effects of Tanguticum Maxim polysaccharide (TMP-1) on TNBS-induced colitis in rats. METHOD: Rats with TNBS/ethanol-induced colitis were used and treated with TMP-1 and dexamethasone (DX). Seventy-two rats, including animals with TNBS-induced colitis, were treated with saline, TMP-1 (100, 200, 400 mg.kg-1) and DX. White blood cells were counted on the fifth day and the rats were killed by ether on the sixth day. SOD activity in serum, MPO and SOD activity of colonic tissue were measured. RESULT: The remarkable effects of TMP-1 at dosage of 200, 400 mg.kg-1 on TNBS-induced colitis were observed. The ulcerative area was diminished and weight of colon was reduced. White blood cell population was reduced, SOD activity in serum and SOD activity of colon tissue were remarkably increased, and, MPO activity of colonic tissue was reduced. CONCLUSION: TMP-1 has significant effects on TNBS-induced colitis in rats with lower side effects, which suggests the effective component of rhubarb on colitis perhaps is TMP. The mechanism of the actions of TMP may relate to its antiflammation, antioxidation and immunoloregulation.

Animals↗

[Morphological, histochemical and immunochemical characteristics of the terminal ileum of patients with ulcerative colitis. Relationship with the development of pouchitis].

UNLABELLED: Pouchitis is the most frequent long-term complication of the ileoanal reservoirs. Its etiology is unknown and it is currently believed to be a recurrence of ulcerative colitis in the mucosa of the ileal reservoir. AIM: To evaluate whether the mucosa of the terminal ileum of patients with ulcerative colitis is different from that of patients free of this disease and whether there are morphological and immunological alterations which might predispose to inflammation of the reservoir. PATIENTS AND METHODS: Colectomy samples from the terminal ileum of 20 patients (12 women, 8 men) with ulcerative colitis who had undergone restorative proctocolectomy with ileoanal reservoir and of 10 controls who had undergone right hemicolectomy for other causes were studied. During follow-up (46.9 months) seven patients were diagnosed with pouchitis (Sandborn > 7). In all patients, morphometric histopathologic, histochemical and immunohistochemical studies of the ileal mucosa were performed. RESULTS: Chronic inflammatory infiltrate and the degree of villous atrophy and of global chronic inflammation were significantly higher in the terminal ileum of patients with ulcerative colitis than in the control group. There were no differences in the mucin content between the two groups and IgA, IgG and B lymphocyte expression was significantly higher in the terminal ileum of patients with ulcerative colitis. Chronic inflammatory infiltrate, degree of atrophy, villous atrophy and of global chronic infiltration, macrophage and CD8 lymphocyte expression were higher in the terminal ileum of patients with pouchitis, but differences was not significant. CONCLUSIONS: The terminal ileum of patients with ulcerative colitis has histopathologic, morphometric and immunohistochemical characteristics that are different from those of patients without this disease. These results may eventually lead to an association between alterations in the ileum and the subsequent development of pouchitis.

Adult↗