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3.
Inflamm Bowel Dis ; 16(2): 296-304, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19824071

ABSTRACT

BACKGROUND: Crohn's disease (CD) is a multifactorial syndrome with genetic and environmental contributions. Mycobacterium avium subspecies paratuberculosis (MAP) has been frequently isolated from mucosal tissues of patients with CD but the cellular immune response to this bacterium has been poorly described. Our aim was to examine the influence of MAP on T-cell proliferation and cytokine responses in patients with inflammatory bowel disease (IBD). METHODS: Peripheral blood mononuclear cells (PBMCs) and mesenteric lymph node cells (MLNCs) were obtained from IBD patients and non-IBD controls. PBMC T-cell proliferation in response to MAP was determined using CFSE labeling and flow cytometry. The specificity of cytokine responses to MAP was controlled by parallel exposure to Listeria monocytogenes (LM) or Salmonella typhimurium (ST). RESULTS: Coincubation of PBMCs with MAP induced significantly more T-cell proliferation (P < 0.0001) in PBMCs isolated from CD patients compared to PBMCs obtained from ulcerative colitis (UC) patients or healthy volunteers. In addition, PBMCs from CD patients secreted significantly higher (P < 0.05) levels of tumor necrosis factor-alpha (TNF-alpha; 2302 +/- 230 pg/mL) and interleukin (IL)-10 (299 +/- 48 pg/mL) in response to MAP compared to UC patients (TNF-alpha: 1219 +/- 411 pg/mL; IL-10: 125 +/- 19 pg/mL) and controls (TNF-alpha: 1447 +/- 173 pg/mL; IL-10: 127 +/- 12 pg/mL). No difference in cytokine responses was observed in response to LM or ST. MLNCs from both CD and UC patients secreted significantly more TNF-alpha and IL-8 in response to MAP compared to MLNCs from non-IBD control patients. CONCLUSIONS: Increased proliferation of T cells and an altered cytokine response suggest that prior exposure to MAP and engagement of the immune system is common in patients with CD. This does not imply causation but does support further examination of this bacterium as an environmental modifying factor.


Subject(s)
Crohn Disease/microbiology , Mycobacterium avium subsp. paratuberculosis , Paratuberculosis/complications , Adolescent , Adult , Aged , Aged, 80 and over , Crohn Disease/complications , Crohn Disease/immunology , Cytokines/blood , Cytokines/physiology , Female , Humans , Interleukin-10/blood , Interleukin-10/physiology , Lymphocyte Activation , Male , Middle Aged , Paratuberculosis/immunology , T-Lymphocytes/physiology , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/physiology , Young Adult
4.
Surg Laparosc Endosc Percutan Tech ; 19(4): e146-8, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19692868

ABSTRACT

The finding of heterotopic gastric mucosa in the rectum is rare, with less than 40 reported cases in the literature. A condition of unknown etiology, several hypotheses exist including infectious and congenital. We report a case of ectopic gastric tissue in the rectum of a 47-year-old female, and her subsequent clinical course. Furthermore for the first time, we present immunohistologic evidence of the presence of Helicobacter pylori in rectal ectopic gastric tissue.


Subject(s)
Choristoma/complications , Choristoma/microbiology , Gastric Mucosa/microbiology , Helicobacter Infections/complications , Helicobacter pylori , Rectal Diseases/complications , Choristoma/diagnosis , Female , Humans , Middle Aged , Rectal Diseases/diagnosis
5.
Am J Gastroenterol ; 104(4): 1013-23, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19259080

ABSTRACT

Ileal pouch-anal anastomosis is the procedure of choice in the surgical management of refractory ulcerative colitis. Pouchitis affects up to 60% of patients following ileal pouch-anal anastomosis for ulcerative colitis. It overlaps significantly with ulcerative colitis such that improvements in our understanding of one will impact considerably on the other. The symptoms are distressing and impinge significantly on patients' quality of life. Despite 30 years of scientific and clinical investigation, the pathogenesis of pouchitis is unknown; however, recent advances in molecular and cell biology make a synergistic hypothesis possible. This hypothesis links interaction between epithelial metaplasia, changes in luminal bacteria (in particular sulfate-reducing bacteria), and altered mucosal immunity. Specifically, colonic metaplasia supports colonization by sulfate-reducing bacteria that produce hydrogen sulfide. This causes mucosal depletion and subsequent inflammation. Although in most cases antibiotics lead to bacterial clearance and symptom resolution, immunogenetic subpopulations can develop a chronic refractory variant of pouchitis. The aims of this paper are to discuss proposed pathogenic mechanisms and to describe a novel mechanism that combines many hypotheses and explains several aspects of pouchitis. The implications for the management of both pouchitis and ulcerative colitis are discussed.


Subject(s)
Bacteria/growth & development , Intestinal Mucosa/pathology , Pouchitis , Anal Canal/microbiology , Anal Canal/pathology , Anal Canal/surgery , Anastomosis, Surgical/methods , Anti-Bacterial Agents/therapeutic use , Colitis, Ulcerative/surgery , Colonic Pouches/microbiology , Colonic Pouches/pathology , Diagnosis, Differential , Humans , Intestinal Mucosa/microbiology , Metaplasia/pathology , Postoperative Complications , Pouchitis/diagnosis , Pouchitis/drug therapy , Pouchitis/etiology
6.
Dis Colon Rectum ; 51(5): 561-7, 2008 May.
Article in English | MEDLINE | ID: mdl-18299930

ABSTRACT

PURPOSE: We characterized the expression of sialomucin and sulphomucin in pouches fashioned for familial adenomatous polyposis and ulcerative colitis. We correlated sulphomucin expression with bacterial colonization and mucosal inflammation. METHODS: Ethical approval and informed consent were obtained. Mucosal biopsies from 9 patients with familial adenomatous polyposis and 12 with ulcerative colitis were obtained. Sulphomucin levels were assessed by using the high iron-diamine stain. Mucous gel layer composition was correlated with villous height, crypt depth, and total mucosal thickness. Mucous gel layer composition was correlated with acute and chronic inflammatory infiltrates. Colonization by a panel of seven bacterial species (including sulphate reducing bacteria) was established and correlated with sulphomucin levels. RESULTS: High-iron-diamine positivity (i.e., sulphomucin expression) was greater in ulcerative colitis pouch mucous gel (2.083 +/- 0.5 vs. 0.556 +/- 0.4, P = 0.003). Sulphomucin expression correlated with reduced crypt depth, villous height, and total mucosal thickness. In the ulcerative colitis group, chronic inflammatory infiltrate scores were significantly greater for high-iron-diamine-positive patients. Colonization by sulphate reducing bacteria was increased in high-iron-diamine-positive patients. CONCLUSIONS: Sulphomucin expression is increased in the mucous gel layer of the ulcerative colitis pouch compared with that of the familial adenomatous polyposis pouch. Sulphomucin expression is associated with colonization by sulphate-reducing bacteria and increased chronic inflammation.


Subject(s)
Adenomatous Polyposis Coli/metabolism , Colitis, Ulcerative/metabolism , Colonic Pouches/microbiology , Mucins/metabolism , Adenomatous Polyposis Coli/surgery , Biopsy , Colitis, Ulcerative/surgery , Female , Humans , Male , Statistics, Nonparametric
7.
Eur J Gastroenterol Hepatol ; 19(4): 347-9, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17353702

ABSTRACT

Over 400 000 cases of tuberculosis existed in Europe in 2002, 1% of which were intestinal tuberculosis. With population migrations on the increase, physicians may have to face an increase in intestinal tuberculosis. One of the attributes of intestinal tuberculosis is its ability to present in nonspecific ways and to mimic other disorders, in particular inflammatory bowel disease. We present a case series of intestinal tuberculosis presenting as inflammatory bowel disease and referred for management to a specialized clinic in inflammatory bowel disease, followed by a discussion of the difficulties encountered with this condition. We highlight the consequences that misdiagnosis can have, in an era where population demographics are changing in Europe and where immunomodulators and biological agents have the potential to do more harm than good.


Subject(s)
Colonic Diseases/microbiology , Crohn Disease/diagnosis , Mycobacterium tuberculosis , Tuberculosis, Gastrointestinal/diagnosis , Adolescent , Adult , Colonoscopy , Diagnosis, Differential , Female , Humans , Male
8.
Surg Infect (Larchmt) ; 7(4): 355-60, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16978078

ABSTRACT

BACKGROUND: Perioperative antimicrobial therapy has demonstrated efficacy in reducing the rate of surgical site infections in clinical trials. With the emergence of antibiotic resistance, the risk of reaction, and the inevitable financial repercussions, use of prophylactic antibiotics is not a panacea, and their misuse may have considerable implications. The aim of this study was to assess the use of antibiotics in the perioperative period in both general and vascular surgery procedures. METHODS: A prospective study was undertaken of 131 patients with a mean age of 43 years (range one month-88 years), of whom 68 (51%) were male, who underwent twenty-seven different general or vascular surgery procedures over a four-week period. Each patient was evaluated from the time of antibiotic commencement through their operative procedure until the treatment was discontinued. RESULTS: A total of 73 patients (54%) received ten antibiotics, with 71 (97%) of these uses being prophylactic. Of the 15 appendectomies performed for uncomplicated appendicitis, the mean number of prophylactic antibiotic doses was 5.3 (range 1-12). Where they were documented, written postoperative directives were not adhered to in 18/27 prescriptions (66%). CONCLUSION: This study has demonstrated a lack of adherence to guidelines in the perioperative administration of antimicrobial agents. In addition, it calls attention to the economic implications of unnecessary prophylaxis.


Subject(s)
Ambulatory Surgical Procedures/methods , Antibiotic Prophylaxis , Perioperative Care/methods , Adolescent , Adult , Aged , Aged, 80 and over , Bacterial Infections/prevention & control , Child , Child, Preschool , Cross Infection/prevention & control , Drug Utilization , Female , Guideline Adherence , Hospitals, University , Humans , Infant , Infant, Newborn , Male , Middle Aged , Practice Guidelines as Topic , Practice Patterns, Physicians' , Prospective Studies , Surgical Wound Infection/prevention & control
9.
Am J Physiol Gastrointest Liver Physiol ; 290(4): G839-45, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16293657

ABSTRACT

Resident host microflora condition and prime the immune system. However, systemic and mucosal immune responses to bacteria may be divergent. Our aim was to compare, in vitro, cytokine production by human mononuclear and dendritic cells (DCs) from mesenteric lymph nodes (MLNs) and peripheral blood mononuclear cells (PBMCs) to defined microbial stimuli. Mononuclear cells and DCs isolated from the MLN (n = 10) and peripheral blood (n = 12) of patients with active colitis were incubated in vitro with the probiotic bacteria Lactobacillus salivarius UCC118 or Bifidobacterium infantis 35624 or the pathogenic organism Salmonella typhimurium UK1. Interleukin (IL)-12, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, and IL-10 cytokine levels were quantified by ELISA. PBMCs and PBMC-derived DCs secreted TNF-alpha in response to the Lactobacillus, Bifidobacteria, and Salmonella strains, whereas MLN cells and MLN-derived DCs secreted TNF-alpha only in response to Salmonella challenge. Cells from the systemic compartment secreted IL-12 after coincubation with Salmonella or Lactobacilli, whereas MLN-derived cells produced IL-12 only in response to Salmonella. PBMCs secreted IL-10 in response to the Bifidobacterium strain but not in response to the Lactobacillus or Salmonella strain. However, MLN cells secreted IL-10 in response to Bifidobacteria and Lactobacilli but not in response to Salmonella. In conclusion, commensal bacteria induced regulatory cytokine production by MLN cells, whereas pathogenic bacteria induce T cell helper 1-polarizing cytokines. Commensal-pathogen divergence in cytokine responses is more marked in cells isolated from the mucosal immune system compared with PBMCs.


Subject(s)
Cytokines/metabolism , Dendritic Cells/metabolism , Inflammatory Bowel Diseases/metabolism , Inflammatory Bowel Diseases/microbiology , Lymph Nodes/metabolism , Lymph Nodes/microbiology , Adult , Bifidobacterium/isolation & purification , Female , Humans , Lactobacillus/isolation & purification , Male , Mesentery/metabolism , Mesentery/microbiology , Middle Aged , Salmonella typhimurium/isolation & purification
10.
Hepatobiliary Pancreat Dis Int ; 4(1): 126-9, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15730936

ABSTRACT

BACKGROUND: The exact mechanism by which cyclooxygenase-2 (COX-2) promotes inflammation in pancreatitis in obscure. This study was undertaken to investigate the role of COX-2 inhibition in an animal model of pancreatitis, a disease process characterized by a systemic inflammatory response and ensuing neutrophil-mediated lung injury. METHODS: Pancreatitis was induced in 24 Sprague-Dawley rats by intraperitoneal injection of 20% L-arginine (500 mg/100 g body weight). The animals were randomized into 3 groups (8 rats in each group): controls and rats with pancreatitis intravenously resuscitated with either normal saline (0.9% NaCl 3 ml/kg)at 24 and 48 hours or COX-2 inhibitor (parecoxib 1 mg/kg). Pancreatic and lung injuries were assessed histologically. Lung injury was assessed utilizing wet:dry ratio and myeloperoxidase activity to indicate pulmonary neutrophil infiltration. A Western blot was used to determine COX-2 protein expression in pancreatic tissue. RESULTS: The animals treated with COX-2 inhibitors displayed significantly less pancreatic and lung injuries than their normal saline counterparts. Histological pancreatic and lung injury scores were significantly reduced (P<0.05) in the COX-2 treated group. Lung wet:dry ratios were significantly improved and pulmonary neutrophil infiltration was attenuated in the COX-2 group (P<0.05). Western blot analysis confirmed attenuated COX-2 protein expression. CONCLUSION: This study shows, for the first time in a rat model, that adjuvant COX-2 inhibition significantly attenuates the severity of both pancreatitis and its associated systemic inflammatory response and end-organ injury.


Subject(s)
Cyclooxygenase Inhibitors/pharmacology , Lung Diseases/pathology , Lung Injury , Pancreatitis/pathology , Prostaglandin-Endoperoxide Synthases/drug effects , Prostaglandin-Endoperoxide Synthases/metabolism , Animals , Arginine , Biopsy, Needle , Blotting, Western , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Disease Models, Animal , Immunohistochemistry , Lung Diseases/complications , Male , Pancreatitis/complications , Probability , Random Allocation , Rats , Rats, Sprague-Dawley , Reference Values , Risk Factors , Sensitivity and Specificity , Statistics, Nonparametric , Up-Regulation
11.
Ann Surg ; 238(2): 249-57, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12894019

ABSTRACT

OBJECTIVE: This study sought to determine whether hypertonic saline (HTS) infusion modulates the host response to bacterial challenge. METHODS: Sepsis was induced in 30 Balb-C mice by intraperitoneal injection of Escherichia coli (5 x 107 organisms per animal). In 10 mice, resuscitation was performed at 0 and 24 hours with a 4 mL/kg bolus of HTS (7.5% NaCl), 10 animals received 4 mL/kg of normal saline (0.9% NaCl), and the remaining animals received 30 mL/kg of normal saline. Samples of blood, spleen, and lung were cultured at 8 and 36 hours. Polymorphonucleocytes were incubated in isotonic or hypertonic medium before culture with E. coli. Phagocytosis was assessed by flow cytometry, whereas intracellular bacterial killing was measured after inhibition of phagocytosis with cytochalasin B. Intracellular formation of free radicals was assessed by the molecular probe CM-H(2)DCFDA. Mitogen-activated protein (MAP) kinase p38 and ERK-1 phosphorylation, and nuclear factor kappa B (NFkappaB) activation were determined. Data are represented as means (SEM), and an analysis of variance test was performed to gauge statistical significance. RESULTS: Significantly reduced bacterial culture was observed in the animals resuscitated with HTS when compared with their NS counterparts, in blood (51.8 +/- 4.3 vs. 82.0 +/- 3.3 and 78.4 +/- 4.8, P = 0.005), lung (40.0 +/- 4.1 vs. 93.2 +/- 2.1 and 80.9 +/- 4.7, P = 0.002), and spleen (56.4 +/- 3.8 vs. 85.4 +/- 4.2 and 90.1 +/- 5.9, P = 0.05). Intracellular killing of bacteria increased markedly (P = 0.026) and superoxide generation was enhanced upon exposure to HTS (775.78 +/- 23.6 vs. 696.57 +/- 42.2, P = 0.017) despite inhibition of MAP kinase and NFkappaB activation. CONCLUSIONS: HTS significantly enhances intracellular killing of bacteria while attenuating receptor-mediated activation of proinflammatory cascades.


Subject(s)
Escherichia coli Infections/therapy , Neutrophils/metabolism , Saline Solution, Hypertonic/therapeutic use , Superoxides/metabolism , Analysis of Variance , Animals , Computer Graphics , Disease Models, Animal , Enzyme Activation , Humans , Male , Mice , Mice, Inbred BALB C , Mitogen-Activated Protein Kinase Kinases/metabolism , NF-kappa B/metabolism , Phagocytosis/drug effects , Random Allocation , Survival Analysis
12.
Arch Surg ; 138(1): 9-14, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12511143

ABSTRACT

HYPOTHESIS: Inhibition of neutrophil-endothelial cell interactions by hypertonic saline (HTS) may confer protection against organ injury in states of immunologic disarray. This study tested the hypothesis that infusion of HTS modulates the development of end-organ injury in a model of lower-torso ischemia-reperfusion injury. DESIGN: Ischemia-reperfusion injury was induced in 30 male Sprague-Dawley rats by infrarenal aortic cross-clamp for 30 minutes, followed by reperfusion for 2 hours. At 0 and 60 minutes of reperfusion, intravenous HTS (7.5% sodium chloride, 4 mL/kg) was administered to 6 rats each, and another 12 received either 4 or 30 mL/kg of isotonic sodium chloride solution. Six rats received HTS, 4 mL/kg, before ischemia. At 2 hours, we assessed liver function, pulmonary injury, neutrophil infiltration (myeloperoxidase activity), endothelial permeability (bronchoalveolar lavage and wet-dry weight ratios), and proinflammatory cytokine levels (tumor necrosis factor alpha and interleukin 6). RESULTS: Infusion with HTS before or after ischemia significantly reduced end-organ injury. Histopathologic pulmonary injury scores were markedly attenuated in the HTS group (5.82 +/- 1.3) and the HTS pretreated group (4.91 +/- 1.6) compared with the isotonic sodium chloride solution groups (8.54 +/- 1.1) (P =.04). Pulmonary neutrophil sequestration (2.07 +/- 0.23) and increased endothelial permeability (4.68 +/- 0.44) were manifest in animals resuscitated with isotonic sodium chloride solution compared with HTS treatment (1.54 +/- 0.19 [P =.04] and 2.06 +/- 0.26 [P =.02]) and pretreatment (1.18 +/- 0.12 [P =.04] and 1.25 +/- 0.07 [P =.002]). In addition, a significant reduction in serum tumor necrosis factor alpha (P =.04) and interleukin 6 (P =.048) levels was observed, whereas HTS resuscitation attenuated the upsurge in aspartate transaminase (P =.03) and alanine transaminase levels (P =.047). CONCLUSIONS: Resuscitation with HTS attenuates the pulmonary edema and tissue injury due to lower-torso ischemia-reperfusion and maintains a more benign immunologic profile.


Subject(s)
Lung Diseases/immunology , Lung Diseases/prevention & control , Reperfusion Injury/immunology , Reperfusion Injury/prevention & control , Saline Solution, Hypertonic/administration & dosage , Animals , Aorta, Thoracic , Cell Communication/immunology , Constriction , Endothelium/physiopathology , Infusions, Intravenous , Interleukin-6/blood , Interleukin-6/immunology , Liver/physiopathology , Lung Diseases/pathology , Lung Diseases/therapy , Male , Models, Animal , Permeability/drug effects , Peroxidase/analysis , Peroxidase/immunology , Rats , Rats, Sprague-Dawley , Reperfusion Injury/pathology , Reperfusion Injury/therapy , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/immunology
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