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Mucosal Biopsies (mucosal + biopsy)
Kinds of Mucosal Biopsies Selected AbstractsColonic left-side increase of eosinophils: a clue to drug-related colitis in adultsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009G. CASELLA Summary Background, The colon shows frequent eosinophilic infiltration in allergic proctocolitis of infants, whereas in adults, eosinophilic infiltration of the colon is less defined and may be found in different conditions including drug-induced colitis, even though the pathological findings are often inconsistent. Aim, To quantify eosinophils in the mucosa of normal controls and to compare them with those of patients with abdominal symptoms related to ,drug colitis'. Methods, Mucosal biopsies were obtained during colonoscopy in 15 controls and in 27 patients with abdominal symptoms, a history of probable ,drug-related colitis' and without obvious causes of eosinophilia. Results, The drugs related to the patient symptoms were nonsteroidal anti-inflammatory drugs (70%), antiplatelet agents (19%) and oestroprogestinic agents (11%). Colonoscopy was normal in 30% of patients and abnormal in 70%. Histology showed low content of inflammatory cells and normal crypt architecture in-patients with endoscopy similar to inflammatory bowel diseases. The eosinophil score was significantly higher in the left side of the colon in the patient group compared with controls. Conclusions, The finding of an increased eosinophil count limited to the left (descending and sigmoid) colon is an important clue towards a diagnosis of drug-related colitis [source] Review article: 5-aminosalicylate formulations for the treatment of ulcerative colitis , methods of comparing release rates and delivery of 5-aminosalicylate to the colonic mucosaALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2008G. R. LICHTENSTEIN Summary Background, Many oral 5-aminosalicylic acid (5-ASA) formulations are designed to maximize 5-ASA release in the colon where it acts topically on the colonic mucosa. Delayed-release formulations and azo-prodrugs minimize 5-ASA absorption in the upper gastrointestinal (GI) tract. Aims, To review methods for assessing 5-ASA release and colonic distribution from oral formulations, and the potential use of this information for guiding clinical decisions. Methods, PubMed and recent conference abstracts were searched for articles describing techniques used to assess 5-ASA release from ulcerative colitis (UC) therapies. Results, In-vitro GI models, although unable to simulate more complex aspects of GI physiology, can provide useful data on 5-ASA release kinetics and bioaccessibility. Gamma-scintigraphy is useful for investigating GI disintegration of different formulations, but may not accurately reflect 5-ASA distribution. Plasma pharmacokinetic studies provide data on systemic exposure, but not on colonic distribution or mucosal uptake. Mucosal biopsies provide direct evidence of colonic distribution and may predict clinical efficacy, but must be interpreted cautiously because of considerable inter-subject variability and other confounding factors. Conclusion, While assessment of 5-ASA release is important, limitations of individual measurement techniques mean that randomized clinical studies in UC patients remain the best guide for dosing and treatment regimen decisions. [source] Halophilic archaea in the human intestinal mucosaENVIRONMENTAL MICROBIOLOGY, Issue 9 2010Andrew P. A. Oxley Summary The human gastrointestinal tract microbiota, despite its key roles in health and disease, remains a diverse, variable and poorly understood entity. Current surveys reveal a multitude of undefined bacterial taxa and a low diversity of methanogenic archaea. In an analysis of the microbiota in colonic mucosal biopsies from patients with inflammatory bowel disease we found 16S rDNA sequences representing a phylogenetically rich diversity of halophilic archaea from the Halobacteriaceae (haloarchaea), including novel phylotypes. As the human colon is not considered a salty environment and haloarchaea are described as extreme halophiles, we evaluated and further discarded the possibility that these sequences originated from pre-colonoscopy saline lavage solutions. Furthermore, aerobic enrichment cultures prepared from a patient biopsy at low salinity (2.5% NaCl) yielded haloarchaeal sequence types. Microscopic observation after fluorescence in situ hybridization provided evidence of the presence of viable archaeal cells in these cultures. These results prove the survival of haloarchaea in the digestive system and suggest that they may be members of the mucosal microbiota, even if present in low numbers in comparison with methanogenic archaea. Investigation of a potential physiological basis of this association may lead to new insights into gastrointestinal health and disease. [source] Detection of Helicobacter species DNA by quantitative PCR in the gastrointestinal tract of healthy individuals and of patients with inflammatory bowel diseaseFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2004Xander W. Huijsdens Abstract In many animal species different intestinal Helicobacter species have been described and a few species are associated with intestinal infection. In humans, the only member of the Helicobacter family which is well described in literature is Helicobacter pylori. No other Helicobacter -associated diseases have definitely been shown in humans. We developed a sensitive quantitative PCR to investigate whether Helicobacter species DNA can be detected in the human gastrointestinal tract. We tested gastric biopsies (including biopsies from H. pylori positive persons), intestinal mucosal biopsies and fecal samples from healthy persons, and intestinal mucosal biopsies from patients with inflammatory bowel disease (IBD) for the presence of Helicobacter species. All gastric biopsies, positive for H. pylori by culture, were also positive in our newly developed PCR. No Helicobacter species were found in the mucosal biopsies from patients with IBD (n=56) nor from healthy controls (n=25). All fecal samples were negative. Our study suggests that Helicobacter species, other than H. pylori, are not present in the normal human gastrointestinal flora and our results do not support a role of Helicobacter species in IBD. [source] Discrimination of Normal Gastric Mucosa from Helicobacter pylori Gastritis using Standard Endoscopes and a Single Observation Site: Studies in Children and Young AdultsHELICOBACTER, Issue 2 2004Yoshiko Nakayama ABSTRACT Background., In the Helicobacter pylori -negative normal stomach, collecting venules are visible in the gastric corpus as numerous minute points. This finding has been termed ,regular arrangement of collecting venules' (RAC). The aim of the present study was to investigate the reliability of the presence of the RAC pattern for discrimination of normal gastric mucosa from H. pylori gastritis in pediatric patients. Methods., Fifty-two consecutive children, adolescents and young adults (male:female 24 : 28; median age 15 years, range 8,29 years) referred for endoscopy and assessed for H. pylori infection were prospectively studied. The lower lesser curvature of the corpus near the incisura was evaluated for the RAC pattern using a standard endoscope with the tip close to, but not in contact with, the gastric surface. Gastric biopsies were taken after the endoscopic observation. Results., In all the 29 RAC-positive patients, active H. pylori gastritis was absent, whereas H. pylori gastritis was found in 20 of 23 RAC-negative patients (86.9%). Conclusions., Identification of the RAC pattern at the lower lesser curvature of the corpus using close observation with a standard endoscope proved to be an effective and practical marker to discriminate normal histology from H. pylori gastritis among both children and young adults. Absence of the RAC pattern should prompt gastric mucosal biopsies despite otherwise normal-appearing gastric mucosa. [source] Anti tumour necrosis-, therapy increases the number of FOXP3+ regulatory T cells in children affected by Crohn's diseaseIMMUNOLOGY, Issue 2 2008Ida Ricciardelli Summary Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. Its pathogenesis is not completely understood, though the prevailing model is that the intestinal flora drives a strong intestinal T helper 1 (Th1)/Th17 type immune response and inflammation in the genetically susceptible host. This leads to overly aggressive T-cell responses to normal bacteria causing tissue damage. Intestinal homeostasis and maintenance of tolerance to harmless antigens in the intestine has been shown to be maintained by CD4+ CD25+ T regulatory cells (Treg) in animal models of inflammatory bowel diseases. Here we investigated whether Infliximab, a chimeric monoclonal antibody directed against tumour necrosis factor (TNF)-, shown to be highly effective in the treatment of CD, has any effect on mucosal CD4+ CD25+ (FOXP3+) Tregs. Colonic mucosal biopsies from children with active Crohn's disease treated in vivo with Infliximab and controls were analysed to determine FOXP3 expression by immunofluorescence and reverse transcription,polymerase chain reaction. We observed that FOXP3+ T cells were significantly reduced in mucosa of CD patients with active disease compared with controls and restored to normal following Infliximab treatment. The frequency of FOXP3+ cells and mRNA expression was significantly increased in CD mucosa from patients treated in vivo with Infliximab compared with CD patients treated with conventional therapies. In conclusion, we show that Infliximab treatment does not solely neutralize soluble TNF-,, but also affects activation and possibly expansion of mucosal regulatory T cells. We suggest that anti TNF-, immunotherapy can also restore mucosal homeostasis in Crohn's disease. [source] Interleukin-16 inhibits interleukin-13 production by allergen-stimulated blood mononuclear cellsIMMUNOLOGY, Issue 1 2006Souad El Bassam Summary Expression of interleukin (IL)-16 is increased in bronchial mucosal biopsies of atopic asthmatics compared to normal controls. The functional significance of increased expression of IL-16 at sites of allergic inflammation is not yet clear. We have previously shown that IL-16 inhibits IL-5 secretion by allergen-stimulated peripheral blood mononuclear cells (PBMC). We investigated whether IL-16 inhibits the production of other T helper 2 cytokines, namely IL-13 and IL-4, by allergen-specific T cells. PBMC from ragweed-sensitive atopic subjects were stimulated with allergen extract for cytokine production in the presence or absence of rhIL-16. Production of cytokines was assessed by enzyme-linked immunosorbent assay and reverse transcription,polymerase chain reaction. To evaluate whether the modulatory effect of IL-16 on cytokine synthesis was mediated by interferon-, (IFN-,), IL-10, IL-12 or IL-18, allergen-stimulated PBMC were cultured in presence of IL-16 and neutralizing concentrations of relevant antibodies. Allergen-stimulated PBMC produced significantly elevated levels of IL-13 (90,740 pg/ml) as compared to unstimulated PBMC (0,375 pg/ml, P < 0·01). Addition of rhIL-16 resulted in down-regulation of IL-13 mRNA expression as well as significantly reduced amounts of IL-13 released by allergen-stimulated PBMC (0,457 pg/ml, P < 0·001), as observed for IL-5. No effect of IL-16 was observed on IL-4 mRNA expression. Treatment with IL-16 resulted in increased levels of IL-10 and IL-18 in allergen-stimulated cell culture. Neutralization of IFN-,, IL-12, IL-10 or IL-18 did not alter the inhibitory effects of IL-16 on IL-13 and IL-5 secretion by allergen-stimulated PBMC. IL-16 did not modify IL-13 synthesis by anti-CD3-stimulated CD4+ T cells, but it significantly reduced the production of IL-5. These data suggest that IL-16 may play an important immunoregulatory role in allergic states in response to allergen. [source] Probiotic administration in patients with ileal pouch,anal anastomosis for ulcerative colitis is associated with expansion of mucosal regulatory cellsINFLAMMATORY BOWEL DISEASES, Issue 5 2008Annamaria Pronio MD Abstract Background: Probiotics have anti-inflammatory effects in patients with inflammatory bowel disease and appear to regulate mucosal immune response through reductions in proinflammatory cytokines. The probiotic VSL#3 prevents pouchitis if started within a week of ileostomy closure and maintains remission following antibacterial treatment in patients with refractory or recurrent pouchitis. However, the efficacy of probiotics and their effects on regulatory cells if started at a greater time after surgery in patients undergoing ileal pouch anal anastomosis (IPAA) for ulcerative colitis are unknown. Methods: We conducted an open-label study in which 31 patients at different periods from surgery without signs and symptoms of pouchitis were randomized to 2 sachets of VSL#3 once daily or no treatment for 12 months. Pouchitis disease activity index (PDAI) was evaluated at baseline and after 3, 6, and 12 months. The percentage of CD4+ T lymphocytes expressing CD25 and the inactive form of transforming growth factor-, [latency-associated peptide (LAP)] were evaluated at baseline and after 3 and 6 months in peripheral-blood mononuclear cells and mucosal biopsies. Variation in tissue interleukin-1, and Foxp3 mRNA expression was also evaluated. Results: During the study period, VSL#3-treated patients showed a significant reduction in PDAI score and a significant increase in the percentage of mucosal CD4+CD25high and CD4+ LAP-positive cells compared with baseline values. Tissue samples at different points showed a significant reduction in IL-1, mRNA expression, and a significant increase in Foxp3 mRNA expression. Conclusions: We conclude that VSL#3 administration in patients with IPAA modulates the PDAI and expands the number of mucosal regulatory T cells. (Inflamm Bowel Dis 2008) [source] Mucosal NOD2 expression and NF-,B activation in pediatric Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 3 2008Laura Stronati PhD Abstract Background: Recent advances in the pathogenesis of Crohn's disease (CD) have suggested that an aberrant innate immune response initiates the cascade of events leading to T-cell activation and to disease development. NOD2 protein, which is mainly expressed by innate immunity cells, appears to play a key role against bacteria by triggering a host defense response through the activation of the transcriptor factor NF-,B and a consequent proinflammatory cytokine production. The present study was aimed at investigating the expression and activity of NOD2, NF-,B, and of 2 proinflammatory cytokines, TNF, and IL-1,, in mucosal biopsies of CD affected children compared to healthy controls. Methods: In all, 22 children with active CD and 10 matched controls were entered in the study. mRNA and protein expressions were detected using reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blot; NF-,B binding activity was assessed by electromobility gel shift assay (EMSA). Results: NOD2 and IL-1, mRNAs were upregulated in CD children. Protein levels of NOD2, TNF,, and nuclear NF-,B, as well as the binding activity of NF-,B to a consensus DNA sequence, were significantly increased in inflamed mucosa of patients as compared to controls. Moreover, NF-,B activity was strongly upregulated in patients also when bound to the NOD2 promoter site. No difference was seen between patients and controls when NF-,B binding activity was determined in the uninflamed tissue. Conclusions: This study suggests that altered mechanisms regulating NOD2 induction, NF-,B activation and cytokine production may contribute to dysregulate the innate immune response underlying pediatric CD. (Inflamm Bowel Dis 2007) [source] Local and systemic interleukin-18 and interleukin-18-binding protein in children with inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 1 2008Steven T. Leach Abstract Background: Interleukin-18 (IL-18) is increased in the inflamed mucosa of patients with Crohn's disease (CD). The balance between this pleiotropic proinflammatory cytokine and its natural inhibitor, IL-18-binding protein (IL-18BP), may contribute to the pathogenesis of inflammatory bowel disease (IBD). Methods: Serum and mucosal biopsies were collected from children with IBD, from children with celiac disease, and from controls. Biopsies were maintained in culture for 24 hours, and supernatant was collected. Serum and supernatant IL-18 and IL-18BPa concentrations were measured by immunoassay. Disease activity score (PCDAI) and standard serum inflammatory markers (albumin, platelets, ESR, and CRP) were recorded. Results: Serum IL-18 was greater in children with CD (537 pg/mL) than in controls (335 pg/mL; P < 0.05) but not in children with ulcerative colitis (UC) or IBD type unclassified (IBDU). Mucosal IL-18 was greater in children with CD and UC/IBDU than in controls (P < 0.01). Serum IL-18BPa was increased in children with CD compared with that in controls (3.9 versus 2.6 ng/mL; P < 0.05), but was not elevated in children with UC/IBDU. Furthermore, calculated free-serum IL-18 was elevated in CD, but not UC/IBDU, compared with that in controls (P = 0.001). Total and free-serum IL-18 were elevated in severe CD relative to in mild/moderate disease. Conclusions: IL-18, produced in the colons of children with IBD, may contribute to local inflammatory changes. Systemic IL-18 level may be a useful indicator of gut inflammation. Furthermore, free IL-18 is greatly elevated in children with CD, suggesting that compensatory increases in IL-18BPa are insufficient. Further exploration of the role of this cytokine in the pathogenesis of IBD is now required. (Inflamm Bowel Dis 2007) [source] Impact of elemental diet on mucosal inflammation in patients with active Crohn's disease: Cytokine production and endoscopic and histological findingsINFLAMMATORY BOWEL DISEASES, Issue 6 2005Takayuki Yamamoto MD Abstract Background: The aim of this study was to examine the impact of elemental diet on mucosal inflammation in Crohn's disease (CD), mainly by cytokine measurements. Methods: Twenty-eight consecutive patients with active CD were treated with an elemental diet (Elental) for 4 weeks. The mucosal biopsies were obtained from the terminal ileum and large bowel before and after treatment. As a control group, mucosal biopsies were obtained from 20 patients without inflammation. Mucosal cytokine concentrations were measured by enzyme-linked immunosorbent assay. Results: After treatment, clinical remission was achieved in 20 patients (71%). Endoscopic healing and improvement rates were 44% and 76% in the terminal ileum and 39% and 78% in the large bowel, respectively. Histologic healing and improvement rates were 19% and 54% in the terminal ileum and 20% and 55% in the large bowel, respectively. Before treatment, the mucosal concentrations of interleukin (IL)-1,, IL-1 receptor antagonist (IL-1ra), IL-6, IL-8, and tumor necrosis factor-, in the ileum and large bowel were significantly higher than in controls. These cytokine concentrations decreased to the levels of control after treatment. IL-1ra/IL-1, ratio in the ileum and large bowel was significantly lower than in controls before treatment. The ratio increased to the level of controls after treatment. The endoscopic and histologic healing of the mucosal inflammation was associated with a decline of the mucosal cytokines and an increase of the IL-1ra/IL-1, ratio. Conclusions: The elemental diet (Elental) reduced mucosal cytokine production and corrected an imbalance between proinflammatory and anti-inflammatory cytokines in CD. [source] Colonic sarcoidosis, infliximab, and tuberculosis: A cautionary taleINFLAMMATORY BOWEL DISEASES, Issue 4 2004Prof. Dario Sorrentino MD Abstract The antitumor necrosis factor, infliximab, has been recently shown to be effective in refractory sarcoidosis including the intestinal form of this disease. We have tried this therapy in a 55-year-old woman under immunosuppressive therapy for longstanding sarcoidosis presenting with abdominal pain apparently caused by a colonic localization of the disease. The latter diagnosis was based, as recommended, on the presence of nonnecrotizing granulomas in mucosal biopsies, the presence of systemic disease, and the careful exclusion of other granulomatous diseases, including tuberculosis. After the first IV infusion (10 mg/kg BW), she quickly improved, but the wellbeing lasted approximately 4 weeks. She then received another dose of infliximab, but she soon developed low-grade fever and weakness and shortly succumbed of miliary tuberculosis. Likely, infliximab precipitated a pre-existing mycobacterial infection of the intestine. Given the likelihood of underdiagnosing intestinal tuberculosis,and the risks associated with infliximab treatment,this case suggests that this drug should be used with extreme caution, if at all, when a diagnosis of colonic sarcoidosis is suspected. [source] Multiple biopsies of normal-looking urothelium in patients with superficial bladder cancer: Are they necessary?INTERNATIONAL JOURNAL OF UROLOGY, Issue 12 2003NAOHIRO FUJIMOTO Abstract Background:, The objective of the study presented here was to assess the usefulness and indications of multiple biopsies of normal-appearing urothelium in patients with superficial bladder cancer. Methods:, Between December 1996 and December 2002, multiple biopsies of normal-appearing bladder mucosa were performed in 100 patients with superficial bladder transitional cell carcinoma. Biopsy specimens were taken from seven different sites in females and nine different sites in males. Results:, In eight of 100 patients, bladder cancers were detected in the biopsy specimens. Three cases were Ta and five were Tis. All of the five patients with carcinoma in situ (CIS) in their biopsy specimens had multiple papillary broad-base tumors and positive urinary cytology. The detection ratio of CIS in patients with these findings was 17.9% (5/28). No concomitant CIS was detected in the 72 patients who had a solitary tumor, pedunculated tumor(s), or negative urinary cytology. Conclusion:, Multiple mucosal biopsies of normal-appearing urothelium are not necessary for all patients with superficial bladder cancer. They are, however, necessary for patients with multiple papillary broad-base tumors and positive urinary cytology. [source] Calcium Channel TRPV6 Expression in Human Duodenum: Different Relationships to the Vitamin D System and Aging in Men and Women,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2006FRCP, Julian RF Walters MA Abstract Intestinal absorption of calcium affects bone mineralization and varies greatly. In human duodenum, expression of the calcium channel TRPV6 was directly related to blood 1,25-dihydroxyvitamin D in men, but effects of age with lower median vitamin D receptor levels were more significant in women. Introduction: The TRPV6 calcium channel/transporter is implicated in animal studies of intestinal calcium absorption, but in humans, its role and relationship to differences in mineral metabolism is unclear. We aimed to characterize TRPV6 expression in human intestine including defining relationships to the vitamin D endocrine system. Materials and Methods: TRPV6 transcript expression was determined in endoscopic mucosal biopsies obtained from normal duodenum. Expression was compared with that in ileum and with in situ hybridization in archival tissues and related to sequence variants in genomic DNA. TRPV6 expression was related in 33 subjects to other transcripts involved in calcium absorption including the vitamin D receptor (VDR) and to blood vitamin D metabolites including 1,25-dihydroxyvitamin D [1,25(OH)2D]. Results: TRPV6 transcripts were readily detected in duodenum but not in ileum. Expression was highest in villous epithelial cells. Sequence variants in the coding and upstream regions of the gene did not affect TRPV6 expression. The relationship between duodenal TRPV6 expression and 1,25(OH)2D differed in men and women. In men, linear regression showed a strong association with 1,25(OH)2D (r = 0.87, p < 0.01), which was unaffected by age. In women, there was no significant overall relationship with 1,25(OH)2D, but there was a significant decrease with age (r = ,0.69, p < 0.001). Individual expression of TRPV6 and VDR was significantly correlated. The group of older women (>50) had lower median levels of both TRPV6 and VDR transcripts than younger women (p < 0.001 and 0.02, respectively). Conclusions: Duodenal TRPV6 expression is vitamin D dependent in men, but not in older women, where expression of TRPV6 and VDR are both reduced. These findings can explain, at least in part, the lower fractional calcium absorption seen in older postmenopausal women. [source] Quantification of mitochondrial DNA mutation loadAGING CELL, Issue 5 2009Laura C. Greaves Summary Mitochondrial DNA (mtDNA) mutations are an important cause of genetic disease and have been proposed to play a role in the ageing process. Quantification of total mtDNA mutation load in ageing tissues is difficult as mutational events are rare in a background of wild-type molecules, and detection of individual mutated molecules is beyond the sensitivity of most sequencing based techniques. The methods currently most commonly used to document the incidence of mtDNA point mutations in ageing include post-PCR cloning, single-molecule PCR and the random mutation capture assay. The mtDNA mutation load obtained by these different techniques varies by orders of magnitude, but direct comparison of the three techniques on the same ageing human tissue has not been performed. We assess the procedures and practicalities involved in each of these three assays and discuss the results obtained by investigation of mutation loads in colonic mucosal biopsies from ten human subjects. [source] Gastroduodenal opportunistic infections and dyspepsia in HIV-infected patients in the era of Highly Active Antiretroviral TherapyJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 1 2009Ana Luiza Werneck-Silva Abstract Background and Aim:, Dyspeptic symptoms are frequently reported by human immunodefficiency virus (HIV)-infected patients under highly active antiretroviral therapy. Whether opportunistic infections are a cause of dyspepsia is still unknown. In this study we prospectively compare the prevalence of gastrointestinal opportunistic infections in dyspeptic versus non-dyspeptic HIV-infected patients with advanced immunodeficiency. Patients and Methods:, Six hundred and ninety HIV-infected patients under highly active antiretroviral therapy underwent esophagogastroduodenoscopy with mucosal biopsies from the stomach and duodenum. Group 1: 500 patients (161 women, 339 men; mean age 38.8 years; mean CD4 count 154.3 cells/mm3 with dyspeptic symptoms such as epigastric pain, nausea, vomiting and fullness. Group 2: 190 patients (169 men, 21 women; mean age 40.7 years; mean CD4 count 171.6 cell/mm3) with no dyspeptic symptoms. Results:, Group 1: Gastrointestinal opportunistic infections were observed in eight (1.6%), and non-opportunistic parasites in two (0.4%), patients. They were: Cytomegalovirus (four patients), Cryptosporidium sp. (two patients), Schistosoma mansoni sp. (one patient), Strongyloides stercoralis (one patient) and Giardia sp. (two patients). In five patients esophagogastroduodenoscopy showed no mucosal lesions. Group 2: Giardia sp. was detected in two patients (1.1%: P = 0.07947). Conclusion:, Gastrointestinal opportunistic infections were shown in a small number of HIV-infected patients under highly active antiretroviral therapy with advanced immunodeficiency. Although gastrointestinal opportunistic infections were detected exclusively in the dyspeptic patient group, they could not be related to these symptoms, since the number of infected patients was not statistically significant. To correctly diagnose opportunistic infections, multiple biopsy specimens may be necessary even from normal-appearing mucosa. [source] Detection of Chlamydia pneumoniae by polymerase chain reaction,enzyme immunoassay in intestinal mucosal biopsies from patients with inflammatory bowel disease and controlsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2002Wangxue Chen Abstract Background and Aim : It has been suggested that Chlamydia is an organism that may have the potential to cause inflammatory bowel disease (IBD) in susceptible individuals. Chlamydia pneumoniae has emerged as an important human pathogen in the last decade. The objective of the present study was to investigate the frequency of the presence of C. pneumoniae DNA in intestinal biopsies from patients with IBD and from non-IBD controls. Methods : The DNA was extracted from 222 colonoscopic biopsies, which were obtained from 11 patients with Crohn's disease (CD), 18 patients with ulcerative colitis (UC) and from 37 non-IBD control patients. The presence of the C. pneumoniae omp1 gene and C. trachomatis 16S rRNA gene was determined using a rapid and sensitive polymerase chain reaction-enzyme immunoassay (PCR-EIA). Results : The C. pneumoniae -specific DNA was detected in 32 (14.4%) of 222 endoscopic biopsies. Among them, C. pneumoniae DNA were found in nine of 42 (21.4%) biopsies from patients with CD, nine of 59 (15.3%) biopsies from patients with UC, and 14 out of 122 (11.4%) biopsies from non-IBD control patients, respectively. Moreover, the percentage of patients with at least one biopsy positive for C. pneumoniae was higher, although not statistically significant, in CD (36.4%) and UC patients (38.9%) compared to non-IBD controls (16.2%). In contrast, C. trachomatis DNA was detected in only two of 222 (0.9%) biopsy samples. Conclusion : The C. pneumoniae DNA was detected in the intestine of both patients with IBD and in non-IBD control patients, probably reflecting the high prevalence of this organism in the environment. The moderate yield of positive biopsies in our IBD patients and the fact that the detection rate of C. pneumoniae DNA was similar in endoscopic biopsies from IBD patients and non-IBD controls does not support a direct role for this organism in the pathogenesis of IBD. © 2002 Blackwell Publishing Asia Pty Ltd [source] Alcohol Stimulates Activation of Snail, Epidermal Growth Factor Receptor Signaling, and Biomarkers of Epithelial,Mesenchymal Transition in Colon and Breast Cancer CellsALCOHOLISM, Issue 1 2010Christopher B. Forsyth Background:, Alcohol consumption is associated with the risk of progressive cancers including colon and breast cancer. The mechanisms for the alcohol-induced aggressive behavior of these epithelial cancer cells have not been fully identified. Epithelial,mesenchymal transition (EMT) is a developmental program recently shown to play a role in cancer progression and metastases. We hypothesized that alcohol might promote cancer progression by inducing EMT in cancer cells and tested this hypothesis by assessing alcohol-stimulated changes in phenotypic markers of EMT as well as the EMT transcription factor Snail and its related cell signaling. Methods:, Colon and breast cancer cell lines and a normal intestinal epithelial cell line were tested as well as colonic mucosal biopsy samples from alcoholic subjects. Cells were treated with alcohol and assessed for EMT-related changes using immunofluorescent microscopy, western blotting, reporter assays, RT-PCR, and knockdown of Snail with siRNA. Results:, We show alcohol upregulated the signature EMT phenotypic marker vimentin as well as matrix metalloprotease (MMP)-2, MMP-7, and MMP-9 and cell migration in colon and breast cancer cells,all characteristics of EMT. Alcohol also stimulated nuclear localization of Snail phosphorylated at Ser246, transcription from a Snail reporter plasmid, and Snail mRNA expression by RT-PCR. Snail siRNA knockdown prevented alcohol-stimulated vimentin expression. In vivo, Snail expression was significantly elevated in colonic mucosal biopsies from alcoholics. Also, we found alcohol stimulated activation of epidermal growth factor receptor (EGFR) signaling and an EGFR inhibitor blocked alcohol-induced cell migration and Snail mRNA expression. Conclusions:, Collectively, our data support a novel mechanism for alcohol promoting cancer progression through stimulating the EMT program in cancer cells via an EGFR-Snail mediated pathway. This study reveals new pathways for alcohol-mediated promotion of cancer that could be targeted for therapy or prevention of alcohol-related cancers. [source] Intestinal Crypt Lesions Associated with Protein-Losing Enteropathy in the DogJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2000M.D. Willard Six dogs were diagnosed with protein-losing enteropathy (PLE). There was no evidence of inappropriate inflammatory infiltrates or lymphangiectasia in multiple mucosal biopsies of the small intestine of 4 of the dogs. The 5th and 6th dogs had obvious lymphangiectasia and a moderate infiltrate of inflammatory cells in the intestinal mucosa. All 6 dogs had a large number of dilated intestinal crypts that were filled with mucus, sloughed epithelial cells, and/or inflammatory cells. Whether PLE occurs in these dogs because of protein lost from the dilated crypts into the intestinal lumen or whether the dilated crypts are a mucosal reaction due to another undetermined lesion that is responsible for alimentary tract protein loss is unknown. However, when large numbers of dilated intestinal crypts are present, they appear to be associated with PLE even if there are no other remarkable lesions in the intestinal mucosa. [source] Ridogrel, a dual thromboxane synthase inhibitor and receptor antagonist: anti-inflammatory profile in inflammatory bowel diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2000Carty Background: Thromboxanes, prostaglandins, reactive oxygen metabolites and pro-inflammatory cytokines are produced in excess in inflammatory bowel disease. Preliminary reports suggest that ridogrel, a thromboxane synthesis inhibitor and receptor blocker, may have therapeutic benefits in ulcerative colitis. Aims: To investigate the anti-inflammatory profile of ridogrel. Methods: The effects of ridogrel on the production of eicosanoids, reactive oxygen metabolites and cytokines by cultured inflamed colorectal mucosal biopsies were made using ELISA and chemiluminescence, reactive oxygen metabolite generation in a cell-free system, and platelet activation using flow cytometry. The effects of oral ridogrel on mucosal release of eicosanoids in two patients with active ulcerative colitis were assessed using rectal dialysis. Results: Ridogrel significantly reduced the release of thromboxane B2, but not prostaglandin E2 or tumour necrosis factor-,, from biopsies (P < 0.01 for 10 ,M ridogrel). Ridogrel showed no direct antioxidant activity but significantly reduced reactive oxygen metabolite production from cultured biopsies (P < 0.01 for 10 ,M ridogrel). Platelet activation in vitro was inhibited by ridogrel (P , 0.05 for , 10 ,M ridogrel). Mean rectal mucosal thromboxane B2 release was reduced to 86% of pre-treatment levels in two patients treated with oral ridogrel. Conclusions: Its inhibition of mucosal production of thromboxane B2, reactive oxygen metabolites, and of platelet activation, suggests that ridogrel could have a therapeutic role in inflammatory bowel disease. [source] Post inflammatory damage to the enteric nervous system in diverticular disease and its relationship to symptomsNEUROGASTROENTEROLOGY & MOTILITY, Issue 8 2009J. Simpson Abstract:, Some patients with colonic diverticula suffer recurrent abdominal pain and exhibit visceral hypersensitivity, though the mechanism is unclear. Prior diverticulitis increases the risk of being symptomatic while experimental colitis in animals increases expression of neuropeptides within the enteric nervous system (ENS) which may mediate visceral hypersensitivity. Our aim was to determine the expression of neuropeptides within the ENS in diverticulitis (study 1) and in patients with symptomatic disease (study 2). Study 1 , Nerves in colonic resection specimens with either acute diverticulitis (AD, n = 16) or chronic diverticulitis (CD, n = 16) were assessed for neuropeptide expression recording % area staining with protein gene product (PGP9.5), substance P (SP), neuropeptide K (NPK), pituitary adenylate cyclase activating polypeptide (PACAP), vasoactive intestinal polypeptide (VIP) and galanin. Study 2 , Seventeen symptomatic and 15 asymptomatic patients with colonic diverticula underwent flexible sigmoidoscopy and multiple peridiverticular mucosal biopsies. Study 1, Neural tissue, as assessed by PGP staining was increased to a similar degree in circular muscle in both AD and CD. The CD specimens showed significant increases in the immunoreactivity of SP, NPK and galanin in both mucosal and circular muscle layer compared with controls. Study 2 , Mucosal histology was normal and PGP9.5 staining was similar between groups however patients with symptomatic diverticular disease demonstrated significantly higher levels of SP, NPK, VIP, PACAP and galanin within the mucosal plexus. Patients with symptomatic diverticular disease exhibit increased neuropeptides in mucosal biopsies which may reflect resolved prior inflammation, as it parallels the changes seen in acute and chronic diverticulitis. [source] Oral and Maxillofacial Pathology: Bcl-2 expression in sequential biopsies of potentially malignant oral mucosal lesions assessed by immunocytochemistryORAL DISEASES, Issue 5 2000RL McAlinden OBJECTIVE: To examine, for the first time Bcl-2 expression in sequential (autogenous) oral mucosal biopsies taken from the same sites in a gender, risk-factor matched, Caucasoid sample, over a 21-year period. DESIGN: Retrospective immunocytochemical longitudinal study of archival serial biopsies. MATERIALS AND METHODS: Computer records were used to identify biopsy specimens derived from 12 patients. These were divided into four groups: (1) Histologically innocuous lesions which remained histologically innocuous. (2) Dysplastic lesions which remained dysplastic. (3) Histologically innocuous lesions which later progressed to squamous cell carcinoma (SCC). (4) Dysplastic lesions which later progressed to SCC. This represented 65 biopsies in total. Bcl-2 expression was studied using mouse antihuman BCL-2 oncoprotein clone 124 (Dako, Denmark). RESULTS: Generally, there was a lack of Bcl-2 immuno-reactivity in the epithelium, with one exception in dysplastic epithelium from a group (3) patient. CONCLUSION: These findings suggest that in our series, Bcl-2 is not expressed early in oral premalignant lesions and appears to contradict previous reports. Possible explanations for this disparity are considered. [source] S-phase fraction and DNA ploidy in oral leukoplakiaANZ JOURNAL OF SURGERY, Issue 7-8 2010Rahul Khanna Abstract Background:, The risk of malignant conversion in oral leukoplakia is well documented. Histological findings are often unreliable and it is difficult to predict on the basis of clinical and histopathological changes which leukoplakic lesion will turn malignant. Methods:, We used the technique of flow cytometry to evaluate the ploidy status, DNA index and S-phase fraction in leukoplakia, oral cancer and normal oral mucosal biopsies and compared it with histological findings. The study was carried out on 30 patients with oral cancer, 60 with leukoplakia and 30 with normal oral mucosal biopsies. Results:, The aneuploidy rate in oral cancers was 64%, for leukoplakia 20%, while all normal mucosal biopsies were diploid. Aneuploid lesions also had a greater S-phase fraction (SPF). The DNA Index (DI) of aneuploid oral cancers was 1.72 and aneuploid leukoplakias was 1.24. Leukoplakia specimens which showed histological evidence of dysplasia had aneuploidy rate of 38%, DI of 1.19 and SPF of 6.2%. The corresponding values for leukoplakia specimens without dysplasia were 14%, 1.09 and 4.1%, respectively. Conclusion:, The method of flow cytometry can be used to identify the subset of leukoplakia patients who are at a higher risk of malignant conversion. These patients could undergo more rigid surveillance or undergo excision biopsy of their lesions. [source] Cyclooxygenase-2 immunoreactivity in collagenous colitisAPMIS, Issue 7 2009SIGNE WILDT Collagenous colitis (CC) is an inflammatory bowel disease of unknown aetiology and pathogenesis. In ulcerative colitis and Crohn's disease, prostaglandins may be involved in the pathogenesis of inflammation, and increased expression of cyclo-oxygenase-2 (COX-2) has been detected. The purpose of this study was to examine the presence and cellular localization of COX-2 in colonic mucosa of patients with CC. Using immunohistochemistry, immunoflouresence and Western blot analysis, COX-2 expression was evaluated in colonic mucosal biopsies from 10 patients with active untreated CC, and compared with samples from eight normal controls, and samples from eight patients with ulcerative colitis or Crohn's disease. Specimens from patients with CC expressed COX-2 protein in increased amounts compared with controls, but similar to patients with ulcerative colitis and Crohn's disease. COX-2 expression was localized to the mononuclear cells of the lamina propria. COX-2 expression was most evident in macrophages. Co-localization of COX-2 and macrophages was increased in number in comparison with controls. In conclusion COX-2 is expressed in increased amounts primarily in the macrophage subpopulation of the inflammatory infiltrate of lamina propria in CC. Increased recruitment of macrophages, increased expression of COX-2 and increased prostaglandin synthesis may be involved in the pathogenesis of CC. [source] Pathological and clinical significance of increased intraepithelial lymphocytes (IELs) in small bowel mucosa,APMIS, Issue 6 2005Review article Intestinal intraepithelial lymphocytes (IELs) belong to a unique T-cell population interspersed between epithelial cells of both the small and large intestine. It is becoming increasingly recognised that an increased number of IELs with a normal villous architecture is within the wide spectrum of histological abnormalities observed in coeliac disease. An increased number of IELs is the earliest pathological change following gluten challenge and a high IEL count may be the only sign of gluten sensitivity. Therefore, the finding of a raised IEL count with normal villous architecture is of sufficient clinical importance to be reported in routine small bowel biopsies. However, it is evident that not all small intestinal biopsy specimens showing increased IELs are explained by gluten sensitivity. Increased IELs in small bowel mucosa have also been associated with autoimmune disorders, tropical sprue, food protein intolerance, Helicobacter pylori -associated gastritis, peptic duodenitis, parasitic and viral infections, as well as the development of intestinal lymphoma. Histological examination of a biopsy specimen of the small bowel remains the diagnostic gold standard for coeliac disease. There will be an ever increasing demand for histological confirmation of gluten sensitivity in patients in whom the classic microscopic appearance of flattened villi may not have fully developed. The more widespread recognition by histopathologists of the pattern of injury manifested by increased numbers of IELs in intestinal biopsy specimens will certainly help in early diagnosis of coeliac disease, lessen diagnostic confusion and influence the modern practice of gastrointestinal tract medicine. This review discusses some of the recent developments in clinical pathology pertaining to increased IELs in small bowel mucosal biopsies. [source] Successful granulocyte-colony stimulating factor treatment of Crohn's disease is associated with the appearance of circulating interleukin-10-producing T cells and increased lamina propria plasmacytoid dendritic cellsCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2009P. J. Mannon Summary Granulocyte-colony stimulating factor (G-CSF) has proved to be a successful therapy for some patients with Crohn's disease. Given the known ability of G-CSF to exert anti-T helper 1 effects and to induce interleukin (IL)-10-secreting regulatory T cells, we studied whether clinical benefit from G-CSF therapy in active Crohn's disease was associated with decreased inflammatory cytokine production and/or increased regulatory responses. Crohn's patients were treated with G-CSF (5 µg/kg/day subcutaneously) for 4 weeks and changes in cell phenotype, cytokine production and dendritic cell subsets were measured in the peripheral blood and colonic mucosal biopsies using flow cytometry, enzyme-linked immunosorbent assay and immunocytochemistry. Crohn's patients who achieved a clinical response or remission based on the decrease in the Crohn's disease activity index differed from non-responding patients in several important ways: at the end of treatment, responding patients had significantly more CD4+ memory T cells producing IL-10 in the peripheral blood; they also had a greatly enhanced CD123+ plasmacytoid dendritic cell infiltration of the lamina propria. Interferon-, production capacity was not changed significantly except in non-responders, where it increased. These data show that clinical benefit from G-CSF treatment in Crohn's disease is accompanied by significant induction of IL-10 secreting T cells as well as increases in plasmacytoid dendritic cells in the lamina propria of the inflamed gut mucosa. [source] Oro-facial granulomatosis: Crohn's disease or a new inflammatory bowel disease?INFLAMMATORY BOWEL DISEASES, Issue 9 2005FRCP, Jeremy Sanderson MD Abstract Background: Oro-facial granulomatosis (OFG) is a rare chronic inflammatory disorder presenting characteristically with lip swelling but also affecting gingivae, buccal mucosa, floor of mouth, and a number of other sites in the oral cavity. Histologically, OFG resembles Crohn's disease (CD), and a number of patients with CD have oral involvement identical to OFG. However, the exact relationship between OFG and CD remains unknown. Methods: Thirty-five patients with OFG and no gut symptoms were identified from a combined oral medicine/gastroenterology clinic. All underwent a standardized assessment of the oral cavity and oral mucosal biopsy to characterize the number of sites affected and the type of inflammation involved. Hematological and biochemical parameters were also recorded. All 35 patients underwent ileocolonoscopy and biopsy to assess the presence of coexistent intestinal inflammation. Results: Ileal or colonic abnormalities were detected in 19/35 (54%) cases. From gut biopsies, granulomas were present in 13/19 cases (64%). An intestinal abnormality was significantly more likely if the age of OFG onset was less than 30 years (P = 0.01). Those with more severe oral inflammation were also more likely to have intestinal inflammation (P = 0.025), and there was also a correlation between the histologic severity of oral inflammation and the histologic severity of gut inflammation (P = 0.047). No relationship was found between any blood parameter and intestinal involvement. Conclusions: Endoscopic and histologic intestinal abnormalities are common in patients with OFG with no gastrointestinal symptoms. Younger patients with OFG are more likely to have concomitant intestinal involvement. In these patients, granulomas are more frequent in endoscopic biopsies than reported in patients with documented CD. OFG with associated intestinal inflammation may represent a separate entity in which granulomatous inflammation occurs throughout the gastrointestinal tract in response to an unknown antigen or antigens. [source] Routine colonic mucosal biopsy and ileoscopy increases diagnostic yield in patients undergoing colonoscopy for diarrheaJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 3 2002IAN F YUSOFF Abstract Background and Aims: In patients undergoing colonoscopy for diarrhea, when the examination is normal, the role of routine mucosal biopsy remains controversial, particularly in the open-access setting. It is uncertain whether routine ileoscopy adds anything to colonoscopy alone. We aimed to assess the yield of mucosal biopsy and ileoscopy in patients with diarrhea. Methods: We retrospectively reviewed all colonoscopies performed for diarrhea over a 9-year period in a tertiary referral center with an open-access service. We then selected cases where the examination was normal and biopsies were performed. The histopathology reports of these selected cases were then reviewed. Results There were 1131 cases identified. The mucosal examination was normal in 465 cases (41%); 362 of these had colonic biopsies performed. Histology was normal in 316 cases (87%) and was non-specific in 28 cases (8%). Significant histopathology was present in 18 cases (5%) with a significantly higher prevalence of microscopic colitis in patients above 60 years old. Ileoscopy was performed in 508 cases and was abnormal in 26 cases (5%). The abnormality on ileoscopy was the sole abnormality in 13 cases (3%). Conclusions Routine colonic mucosal biopsy and ileoscopy each identify significant additional pathology in 5% of cases when investigating patients with diarrhea, and are recommended as routine practice in this setting. We found ileal biopsy unhelpful when ileoscopy was normal. © 2002 Blackwell Science Asia Pty Ltd [source] Lichenoid and granulomatous stomatitis: an entity or a non-specific inflammatory process?JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 5 2006C. Max Robinson Background:, The presence of lichenoid or granulomatous inflammation in an oral mucosal biopsy usually suggests a distinct range of diagnostic possibilities. However, the presence of both patterns of inflammation in the same biopsy is uncommon. Methods:, A clinico-pathological study of six patients. Results:, All the patients in this study presented with similar mucosal lesions of the upper lip. Microscopically the lesions were characterized by the presence of lichenoid inflammation with concomitant granulomatous inflammation. The lesions were persistent and refractory to treatment with steroid medications, but remained localized and did not appear to herald the onset of systemic inflammatory or neoplastic disease. Conclusion:, We propose the designation ,lichenoid and granulomatous stomatitis' for the cases described in this study. The clinico-pathological features of a subset of these cases suggest an unusual drug eruption. [source] A systematic review on the clinical diagnosis of gastrointestinal stromal tumorsJOURNAL OF SURGICAL ONCOLOGY, Issue 5 2008Marco Scarpa MD Abstract Background The aim of this work was to assess the prevalence of symptoms of gastrointestinal stromal tumors (GISTs) and the diagnostic yield of clinical procedures for its diagnosis. Methods Medical databases were consulted between 1998 and 2006 for potentially relevant publications. All studies dealing with the clinical presentation of GIST and related diagnostic procedures were included. Two researchers worked independently on the study selection, quality assessment, data extraction, and analysis phases of the study. Results Forty-six observational studies were included with a total of 4,534 patients. Gastrointestinal bleeding was the most common clinical presentation. Twenty studies provided adequate information on the diagnostic yield of various procedures. The pooled diagnostic yield of endoscopy,+,mucosal biopsy and of intestinal contrast radiography was 33.8% (0,100%) and 35.1% (11,100%), respectively, while that of EUS and that of EUS-FNA was 68.7% (40,100%) and 84.0% (73.8,100%), respectively. Abdominal CT scan and MRI had similar pooled diagnostic yields: 73.6% (34.8,100%), and 91.7% (75,100%), respectively. Conclusion Endoscopy,+,mucosal biopsy should be reserved to patients with gastrointestinal bleeding. EUS-FNA provides direct visualization of the neoplasm and adequate samples for molecular diagnosis. EUS, abdominal CT and MRI may be considered valid alternatives whenever EUS-FNA is unavailable or a cytological diagnosis is unnecessary. J. Surg. Oncol. 2008;98:384,392. © 2008 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||