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ABSTRACT: INTRODUCTION: Single port laparoscopic surgery has been increasingly used for complex surgical procedures. To our knowledge, this is the first published report of a single port laparoscopic subtotal colectomy and ileostomy in an adolescent patient with ulcerative colitis. CASE REPORT: A 13-year old female patient with ulcerative colitis resistant to maximal medical therapy underwent a single port laparoscopic subtotal colectomy and ileostomy. Both the procedure and the postoperative recovery were uneventful and the patient was discharged home on the sixth postoperative day. Follow-up at 3 and 8weeks after surgery identified no early complications with a 4kg weight gain. DISCUSSION: Single port laparoscopic surgery is feasible in the adolescent population if there is appropriate surgical expertise and strict patient selection.
Journal of Crohn s and Colitis 04/2012; · 2.57 Impact Factor
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ABSTRACT: Enterotoxin-producing Staphylococcus aureus may cause severe inflammatory intestinal disease, particularly in infants or immunodeficient or elderly patients. They are also recognized to be associated with sudden infant death syndrome. Little is known, however, about mucosal responses to staphylococci.
The mucosal lesion in three infants with staphylococcal enterocolitis was assessed by immunohistochemistry and electron microscopy. The organisms underwent extensive molecular analysis. Their toxins were assessed for capacity to induce T-cell activation and host mucosal responses examined by in vitro organ culture. Epithelial responses were studied by coculture with HEp-2 and Caco-2 cells.
Intestinal biopsies from the patients showed marked epithelial damage with mucosal inflammation. The three staphylococci, representing two distinct clones, were methicillin-sensitive, producing SEG/I enterotoxins and Rho-inactivating EDIN toxins. Their enterotoxins potently activated T cells, but only whole organisms could induce in vitro enteropathy, characterized by remarkable epithelial desquamation uninhibited by tacrolimus. EDIN-producing staphylococci, but not their supernatants, induced striking cytopathy in HEp-2 epithelial cells but not in Caco-2 cells. Although HEp-2 and Caco-2 cells produced similar IL-8, CCL20, and cathelicidin LL37 responses upon bacterial exposure, only Caco-2 cells expressed mRNA for the β-defensins HBD2 and HBD3, while HEp-2 cells were unable to do so.
Staphylococci induce enterocolitis by a combination of direct enterocyte cytopathy mediated by EDIN toxins, disrupting the epithelial barrier, and enterotoxin superantigen-induced mucosal T-cell activation. Gut epithelial production of β-defensins may contribute to host defense against invasive staphylococcal disease.
Inflammatory Bowel Diseases 09/2011; 18(4):624-40. · 4.86 Impact Factor
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ABSTRACT: To assess feasibility of a finger prick-based kit as method for self-testing of first and second-degree relatives of coeliac disease (CD) patients.
A total number of 379 subjects were invited to participate in this study, consisting of 197 first-degree and 182 second-degree relatives of CD patients. The self-testing kit (Biocard™) was sent out with included instructions for use. Completed tests were sent back to the study coordinator for assessment.
One hundred and ninety-six invited relatives carried out the Biocard™ test at home. Amongst these, 70% were children. In 97% of the cases the test was performed correctly. Three tests revealed a positive result, all of which were later confirmed by serology and histology as coeliac disease.
Our study indicates that Biocard™ test is a reliable, easy to use and well-accepted tool for home testing of first- and second-degree relatives of CD patients.
World Journal of Gastroenterology 04/2011; 17(14):1840-3. · 2.47 Impact Factor
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Matthias Zilbauer,
Andreas Jenke,
Gundula Wenzel,
Jan Postberg,
Andreas Heusch,
Alan D Phillips,
Gabriele Noble-Jamieson, Franco Torrente,
Camilla Salvestrini,
Robert Heuschkel,
Stefan Wirth
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ABSTRACT: Human beta-defensins (hBDs) are antimicrobial peptides known to play a major role in intestinal innate host defence. Altered mucosal expression of hBDs has been suggested to be implicated in chronic inflammatory bowel disease pathogenesis. However, little is known about expression of these peptides in children.
Intestinal biopsies were obtained from the duodenum (n = 88), terminal ileum (n = 90) and ascending colon (n = 105) of children with Crohn's disease (n = 26), ulcerative colitis (n = 11) and healthy controls (n = 16). Quantitative real-time (RT) PCR was performed and absolute mRNA copy numbers analyzed for hBD1-3 as well as inflammatory cytokines IL-8 and TNF-alpha.
Significant induction of hBD2 and hBD3 was observed in the inflamed terminal ileum and ascending colon of IBD children. In the ascending colon induction of hBD2 was found to be significantly lower in children with Crohn's disease compared to ulcerative colitis. A strong correlation was found between inducible defensins hBD2 and 3 and the inflammatory cytokines IL-8 and TNF-alpha, both in the terminal ileum and ascending colon.
Our study demonstrates distinct changes in hBD expression throughout the intestinal tract of children with IBD, lending further support for their potential role in disease pathogenesis.
PLoS ONE 01/2010; 5(10):e15389. · 4.09 Impact Factor
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ABSTRACT: Although it is a well-described syndrome in infants, eosinophilic colitis is a loosely defined and poorly understood diagnosis in older children. The aims of this case series were to characterise colonic eosinophilia in children and to determine whether it represents a distinct clinicopathological condition.
We retrospectively reviewed symptomatic children older than 12 months with the principal diagnosis of colonic eosinophilia who presented between January 2000 and February 2007 (n = 38) and a further 10 children whose colonic biopsies were reported as histologically normal. The eosinophil density in all available gastrointestinal biopsies (n = 620) of these children was determined using a validated quantitative morphometric method. Patients were subdivided according to mean colonic eosinophil levels into 3 groups (marked, moderate, or minimal colonic eosinophilia). The following patient information was obtained and compared among patient groups: symptoms prompting endoscopy, atopic history, outcome, serum C-reactive protein and total immunoglobulin E (IgE) levels, erythrocyte sedimentation rate, blood eosinophil count, and endoscopic findings.
In all 3 patient groups, there was a colonic gradient of decreasing eosinophil density from caecum to rectum. Upper gastrointestinal tract biopsies did not exhibit eosinophilia. Although a significant association (P = 0.03) between abnormal total IgE levels and moderate or severe colonic eosinophilia was found, there was no significant difference (P > 0.05) in other patient characteristics. Furthermore, follow-up data did not show a consistent relation between eosinophil density and progression of symptoms.
We find no association between "eosinophilic colitis," defined as a histologically demonstrated marked colonic eosinophilia, and symptoms, history of atopy, inflammatory markers, or clinical outcome.
Journal of pediatric gastroenterology and nutrition 07/2009; 49(2):208-15. · 2.18 Impact Factor
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Beatrice Amadi,
Andrew O Fagbemi,
Paul Kelly,
Mwiya Mwiya, Franco Torrente,
Camilla Salvestrini,
Richard Day,
Michael H Golden,
Erik A Eklund,
Hudson H Freeze,
Simon H Murch
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ABSTRACT: Kwashiorkor, a form of severe malnutrition with high mortality, is characterized by edema and systemic abnormalities. Although extremely common, its pathophysiology remains poorly understood, and its characteristic physical signs are unexplained.
Because kwashiorkor can develop in protein-losing enteropathy, which is caused by a loss of enterocyte heparan sulfate proteoglycan (HSPG), and previous observations suggest abnormal sulfated glycosaminoglycan (GAG) metabolism, we examined whether intestinal GAG and HSPG are abnormal in children with kwashiorkor.
Duodenal biopsy samples collected from Zambian children with marasmus (n = 18), marasmic kwashiorkor (n = 8), and kwashiorkor (n = 15) were examined for expression of HSPG, GAGs, and immunologic markers and compared against reference samples from healthy UK control children. GAG and HSPG expression density and inflammatory cell populations were quantitated by computerized analysis.
The kwashiorkor group was less wasted and had a lower HIV incidence than did the other groups. All duodenal biopsy samples showed inflammation compared with the histologically uninflamed control samples. Biopsy samples from marasmic children had greater inflammation and greater CD3+ and HLA-DR (human leukocyte antigen DR)-positive cell densities than did samples from children with kwashiorkor. Expression of both HSPG and GAGs was similar between marasmic and well-nourished UK children but was markedly lower in children with kwashiorkor in both the epithelium and lamina propria. Although underglycosylated and undersulfated, epithelial syndecan-1 protein was normally expressed in kwashiorkor, which confirmed that abnormalities arise after core protein synthesis.
Intestinal HSPG loss occurs in kwashiorkor, which may precipitate protein-losing enteropathy to cause edema. If occurring systemically, impaired HSPG expression could cause several previously unexplained features of kwashiorkor. We speculate that a genetic predisposition to reduced HSPG biosynthesis may offer a contrasting selective advantage, by both diminishing protein catabolism during transient undernutrition and protecting against specific infectious diseases.
American Journal of Clinical Nutrition 01/2009; 89(2):592-600. · 6.67 Impact Factor
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Camilla Salvestrini,
John A McGrath,
Linda Ozoemena,
Khaled Husain,
Eman Buhamrah,
Nasim Sabery,
Alan Leichtner,
Paul A Rufo,
Antonio Perez-Atayde,
Cate H Orteu, Franco Torrente,
Robert B Heuschkel,
Michael A Thomson,
Simon H Murch
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ABSTRACT: Mutations in alpha6 or beta4 integrins (ITGA6, ITGB4) are known to cause junctional epidermolysis bullosa with pyloric atresia (JEB-PA), often lethal in infancy through skin desquamation. There is 1 report of pyloric atresia associated with a desquamatory enteropathy but without skin disease, of unknown molecular basis.
We report 2 Kuwaiti siblings with pyloric atresia and life-threatening intestinal desquamation without significant skin abnormality. The older sibling died of intractable diarrhoea, and the younger sibling suffered episodes of massive protein-losing enteropathy, triggered by viral infections, in addition to obstructive uropathy. Mutation analysis was performed for ITGA6 and ITGB4 and expression of ITGA6 and ITGB4 protein was examined in skin and intestinal biopsies. Her serum also was incubated with normal intestine.
We identified a novel mutation in ITGB4, with homozygous deletion of a single residue (isoleucine 1314) within the intracellular plectin-binding domain. Expression of ITGA6 and ITGB4 within skin, duodenal, and colonic epithelium was normal or minimally reduced, in contrast to previous reports. Biopsies taken during relapse showed accumulation of immunoglobulin G and C1q within intestinal basement membrane, whereas immunoglobulin G from her serum bound to basement membrane of normal small intestine. Immunomodulatory therapy induced significant improvement following relapses.
ITGB4 mutation may induce a desquamative enteropathy in infancy without significant skin disease. A history of pyloric atresia is important in infants with severe chronic diarrhoeal disease and should prompt investigation for JEB-PA associated mutations. Acquired immune responses may exacerbate primary genetic disorders of epithelial adhesion and immunomodulatory therapy may be beneficial.
Journal of pediatric gastroenterology and nutrition 12/2008; 47(5):585-91. · 2.18 Impact Factor
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Camilla Salvestrini,
John A McGrath,
Linda Ozoemena,
Khaled Husain,
Eman Buhamrah,
Nasim Sabery,
Alan Leichtner,
Paul A Rufo,
Antonio Perez-Atayde,
Cate H Orteu, Franco Torrente,
Robert B Heuschkel,
Michael A Thomson,
Simon H Murch
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ABSTRACT: Background: Mutations in α6 or β4 integrins (ITGA6, ITGB4) are known to cause junctional epidermolysis bullosa with pyloric atresia (JEB-PA), often lethal in infancy through skin desquamation. There is 1 report of pyloric atresia associated with a desquamatory enteropathy but without skin disease, of unknown molecular basis.
Patients and Methods: We report 2 Kuwaiti siblings with pyloric atresia and life-threatening intestinal desquamation without significant skin abnormality. The older sibling died of intractable diarrhoea, and the younger sibling suffered episodes of massive protein-losing enteropathy, triggered by viral infections, in addition to obstructive uropathy. Mutation analysis was performed for ITGA6 and ITGB4 and expression of ITGA6 and ITGB4 protein was examined in skin and intestinal biopsies. Her serum also was incubated with normal intestine.
Results: We identified a novel mutation in ITGB4, with homozygous deletion of a single residue (isoleucine 1314) within the intracellular plectin-binding domain. Expression of ITGA6 and ITGB4 within skin, duodenal, and colonic epithelium was normal or minimally reduced, in contrast to previous reports. Biopsies taken during relapse showed accumulation of immunoglobulin G and C1q within intestinal basement membrane, whereas immunoglobulin G from her serum bound to basement membrane of normal small intestine. Immunomodulatory therapy induced significant improvement following relapses.
Conclusions: ITGB4 mutation may induce a desquamative enteropathy in infancy without significant skin disease. A history of pyloric atresia is important in infants with severe chronic diarrhoeal disease and should prompt investigation for JEB-PA associated mutations. Acquired immune responses may exacerbate primary genetic disorders of epithelial adhesion and immunomodulatory therapy may be beneficial.
Journal of Pediatric Gastroenterology and Nutrition 10/2008; 47(5):585-591. · 2.30 Impact Factor
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Li Bai,
Stephanie Schüller,
Andrew Whale,
Aurelie Mousnier,
Olivier Marches,
Lei Wang,
Tadasuke Ooka,
Robert Heuschkel, Franco Torrente,
James B Kaper,
Tânia A T Gomes,
Jianguo Xu,
Alan D Phillips,
Gad Frankel
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ABSTRACT: Typical enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) employ either Nck, TccP/TccP2, or Nck and TccP/TccP2 pathways to activate the neuronal Wiskott-Aldrich syndrome protein (N-WASP) and to trigger actin polymerization in cultured cells. This phenotype is used as a marker for the pathogenic potential of EPEC and EHEC strains. In this paper we report that EPEC O125:H6, which represents a large category of strains, lacks the ability to utilize either Nck or TccP/TccP2 and hence triggers actin polymerization in vitro only inefficiently. However, we show that infection of human intestinal biopsies with EPEC O125:H6 results in formation of typical attaching and effacing lesions. Expression of TccP in EPEC O125:H6, which harbors an EHEC O157-like Tir, resulted in efficient actin polymerization in vitro and enhanced colonization of human intestinal in vitro organ cultures with detectable N-WASP and electron-dense material at the site of bacterial adhesion. These results show the existence of a natural category of EPEC that colonizes the gut mucosa using Nck- and TccP-independent mechanisms. Importantly, the results highlight yet again the fact that conclusions made on the basis of in vitro cell culture models cannot be extrapolated wholesale to infection of mucosal surfaces and that the ability to induce actin polymerization on cultured cells should not be used as a definitive marker for EPEC and EHEC virulence.
Infection and immunity 02/2008; 76(1):361-8. · 4.21 Impact Factor
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ABSTRACT: There is increasing recognition that Henoch-Schonlein purpura may present in an atypical form in which gastrointestinal symptoms may predominate, and classic cutaneous changes may be delayed or absent. This may lead to significant diagnostic delay. We report the case of a 9-year-old girl who presented acutely with life-threatening gastrointestinal haemorrhage from multiple intestinal sites, with no skin rash and only mild evidence of renal involvement. Henoch-Schonlein purpura was confirmed by finding IgA deposition on vessels within gastric and duodenal mucosa, while immunohistochemistry also identified dense focal T cell infiltration in gastric mucosa and within duodenal epithelium. After initial stabilisation, the patient became shocked due to further gastrointestinal haemorrhage. Isotope bleeding scan identified multiple bleeding sites. Her endoscopically confirmed gastritis was sufficiently severe to preclude corticosteroids, and she was thus treated with intravenous immunoglobulin. This therapy induced prompt and sustained resolution of symptoms, and she has remained well since. Our patient's response concords with previous reports in corticosteroid-resistant cases to suggest that severe intestinal Henoch-Schonlein purpura may respond preferentially to intravenous immunoglobulin (IVIG) therapy. In severe cases where there is significant gastritis, IVIG provides an effective alternative to corticosteroids that may be employed as first-line therapy.
European Journal of Pediatrics 10/2007; 166(9):915-9. · 1.88 Impact Factor
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ABSTRACT: Enterohaemorrhagic Escherichia coli (EHEC) are an important cause of diarrhoeal and renal disease in man. Studies of a single prototypic O157 : H7 strain have shown tropism for follicle-associated epithelium (FAE) of distal ileal Peyer's patches without colonization of either small or large intestine. This study determined tropism in a range of Shiga toxin (Stx)-negative EHEC strains and looked for factors that might induce colonic colonization using human in vitro intestinal organ culture (IVOC). An FAE-restricted colonization was confirmed in two strains; four strains additionally colonized ileal villous surfaces, and adhesion to proximal small intestinal FAE was observed. All strains showed minimal adhesion to non-FAE regions of proximal small intestinal and to the transverse colon. Extensive large-bowel IVOC studies using three O157 : H7 strains, an O26 : H11 and an O103 : H2 strain, and tissue from caecum to rectum found colonization and attaching/effacing lesion formation in only 4 of 113 (3.5 %) IVOCs. Colonic adhesion was not enhanced by altering the IVOC technique or environment. Co-incubation of O157 : H7-infected ileal FAE with colonic samples enhanced colonic colonization, producing a novel, non-intimate adhesive phenotype. Thus, in the initial stages of colonization Stx-negative EHEC preferentially infect FAE and villi of the terminal ileal region ex vivo; colonic colonization is infrequently observed as an initial event but may represent a subsequent stage of infection.
Microbiology 04/2007; 153(Pt 3):794-802. · 3.06 Impact Factor
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ABSTRACT: Shiga toxins are associated with haemolytic uraemic syndrome but human intestinal epithelium does not express the Gb3 receptor. We describe Gb3 expression and Shiga toxin binding in histologically normal intestine and demonstrate that the pattern is unaltered in inflammatory disease states. Gb3 expression and Shiga toxin binding were identified in Paneth cells in both normal and inflamed mucosae.
Microbes and Infection 02/2007; 9(1):35-9. · 3.10 Impact Factor
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ABSTRACT: A lymphocytic enterocolitis has been reported in a cohort of children with autistic spectrum disorder (ASD) and gastrointestinal (GI) symptoms. This study tested the hypothesis that dysregulated intestinal mucosal immunity with enhanced pro-inflammatory cytokine production is present in these ASD children. Comparison was made with developmentally normal children with, and without, mucosal inflammation. Duodenal and colonic biopsies were obtained from 21 ASD children, and 65 developmentally normal paediatric controls, of which 38 had signs of histological inflammation. Detection of CD3+ lymphocyte staining for spontaneous intracellular TNFalpha, IL-2, IL-4, IFNgamma, and IL-10, was performed by multicolor flow cytometry. Duodenal and colonic mucosal CD3+ lymphocyte counts were elevated in ASD children compared with noninflamed controls (p<0.03). In the duodenum, the proportion of lamina propria (LP) and epithelial CD3(+)TNFalpha+ cells in ASD children was significantly greater compared with noninflamed controls (p<0.002) but not coeliac disease controls. In addition, LP and epithelial CD3(+)IL-2+ and CD3(+)IFNgamma+, and epithelial CD3(+)IL-4+ cells were more numerous in ASD children than in noninflamed controls (p<0.04). In contrast, CD3(+)IL-10+ cells were fewer in ASD children than in noninflamed controls (p<0.05). In the colon, LP CD3(+)TNFalpha+ and CD3(+)IFNgamma+ were more frequent in ASD children than in noninflamed controls (p<0.01). In contrast with Crohn's disease and non-Crohn's colitis, LP and epithelial CD3(+)IL-10+ cells were fewer in ASD children than in nondisease controls (p<0.01). There was a significantly greater proportion of CD3(+)TNFalpha+ cells in colonic mucosa in those ASD children who had no dietary exclusion compared with those on a gluten and/or casein free diet (p<0.05). There is a consistent profile of CD3+ lymphocyte cytokines in the small and large intestinal mucosa of these ASD children, involving increased pro-inflammatory and decreased regulatory activities. The data provide further evidence of a diffuse mucosal immunopathology in some ASD children and the potential for benefit of dietary and immunomodulatory therapies.
Journal of Clinical Immunology 12/2004; 24(6):664-73. · 3.08 Impact Factor
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ABSTRACT: Immunohistochemistry allowed recent recognition of a distinct focal gastritis in Crohn's disease. Following reports of lymphocytic colitis and small bowel enteropathy in children with regressive autism, we aimed to see whether similar changes were seen in the stomach. We thus studied gastric antral biopsies in 25 affected children, in comparison to 10 with Crohn's disease, 10 with Helicobacter pylori infection, and 10 histologically normal controls. All autistic, Crohn's, and normal patients were H. pylori negative.
Snap-frozen antral biopsies were stained for CD3, CD4, CD8, gammadelta T cells, HLA-DR, IgG, heparan sulphate proteoglycan, IgM, IgA, and C1q. Cell proliferation was assessed with Ki67.
Distinct patterns of gastritis were seen in the disease states: diffuse, predominantly CD4+ infiltration in H. pylori, and focal-enhanced gastritis in Crohn's disease and autism, the latter distinguished by striking dominance of CD8+ cells, together with increased intraepithelial lymphocytes in surface, foveolar and glandular epithelium. Proliferation of foveolar epithelium was similarly increased in autism, Crohn's disease and H. pylori compared to controls. A striking finding, seen only in 20/25 autistic children, was colocalized deposition of IgG and C1q on the subepithelial basement membrane and the surface epithelium.
These findings demonstrate a focal CD8-dominated gastritis in autistic children, with novel features. The lesion is distinct from the recently recognized focal gastritis of Crohn's disease, which is not CD8-dominated. As in the small intestine, there is epithelial deposition of IgG.
The American Journal of Gastroenterology 05/2004; 99(4):598-605. · 7.28 Impact Factor
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ABSTRACT: Inflammatory intestinal pathology has been reported in children with regressive autism (affected children). Detailed analysis of intestinal biopsies in these children indicates a novel lymphocytic enterocolitis with autoimmune features; however, links with cognitive function remain unclear. To characterize further, the nature and extent of this disease we examined the mucosal infiltrate using flow cytometry. Duodenal, ileal, and colonic biopsies were obtained from 52 affected children, 25 histologically normal, and 54 histologically inflamed, developmentally normal controls. Epithelial and lamina propria lymphocyte populations were isolated and examined by multicolor flow cytometry. Adjacent biopsies were assessed by semiquantitative histopathology. At all sites, CD3(+) and CD3(+)CD8(+) IEL as well as CD3(+) LPL were significantly increased in affected children compared with developmentally normal noninflamed control groups (p<0.01) reaching levels similar to inflamed controls. In addition, two populations--CD3(+)CD4(+) IEL and LP CD19(+) B cells--were significantly increased in affected children compared with both noninflamed and inflamed control groups including IBD, at all sites examined (p<0.01). Histologically there was a prominent mucosal eosinophil infiltrate in affected children that was significantly lower in those on a gluten- and casein-free diet, although lymphocyte populations were not influenced by diet. The data provide further evidence of a pan-enteric mucosal immunopathology in children with regressive autism that is apparently distinct from other inflammatory bowel diseases.
Journal of Clinical Immunology 11/2003; 23(6):504-17. · 3.08 Impact Factor
