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Abdominal pain is a common presentation of giardia lamblia in children and adolescents
A944
AGA ABSTRACTS
• DOES APPENDECTOMY REALLY PROTECT A G A I N S T ULCERATIVE COLITIS? B L Woods, E N Steinberg, C A Homung, R Vasudeva, C W Howden, Department of Medicine, University of South Carolina School of Medicine, Columbia, SC. Aims : This study was designed to examine the recent European claim (Rutgeerts et al., Gastroenterol 1994; 106: 1251-3) that appendectomy protects against the development of ulcerative colitis (UC). The influence of appendectomy and tonsillectomy (also removal of lymphoid tissue) on development of UC and Crohn's disease (CD) were studied. Methods : Patients with UC or CD attending out-patient clinics of two teaching hospitals were interviewed by telephone, or their charts were reviewed. Patients with hypertension served as controls. Patients and controls were asked about previous appendectomy and tonsillectomy and data were also collected on age, sex, race, other past medical and surgical history, smoking and alcohol use, 65 patients with UC, 51 with CD, and 1O3 controls were evaluated. Mean ages were 53.9, 42.5, and 55.4 respectively. Results : Appendectomy had been performed in 10/65 UC patients (15.4%), 8/51 CD patients (15.7%) and 10/103 controls (9.7%). Odds ratio (OR) for development of UC after appendectomy was 1.69 (95% CI = 0.60-4.74 ; P=0.27). OR for CD was 1.73 (95% CI = 0.57-5.19 ; P=0.19). OR for either UC or CD was 1.71 (95% CI = 0,70-4.27 ; P=0.19). ORs for development of UC, CD and either UC or CD after tonsillectomy were 0.71 (95% CI = 0.30-1.68 ; P=0.39), 1.07 (95% CI = 0.45-2.54 ; P=0.87) and 0.86 (95% CI = 0.43-1.73 ; P=0:65) i'espectively. Conclusions : The results of this US-based study do not support the recent observation that appendectomy protects against development of UC. In addition, appendectomy does not protect against CD. Tonsillectomy does not protect against development of UC or CD.
• INFLAMMATORY MACROPHAGES BUT NOT RESIDENT MACROPHAGES EXPRESS MEMBRANE-BOUND CD14, A RECEPTOR FOR LIPOPOLYSACCHARIDE, IN A MOUSE MODEL OF ULCERATIVE COLITIS. A. Wozniak, E. Van de Pol, W.F. Doe. Div. of Clinical Sciences, John Curiin School of Medical Research, Australian N~ational University, Canberra, ACT, Australia. CD14 is a receptor for LPS complexed with a soluble LPS-binding protein (LBP) and is found on the surface of monocytes, macmphages and neutrophlls and in a soluble form in serum. Recent findings suggest that other bacterial constituents may also bind and activate the CD14 receptor. Binding of LPS-LBP complexes to CD14 at nanomolar concentrations leads to cell activation and release of proinflammatory cytokines. Since large quantities of LPS and other bacterial products are present in the colon and terminal ileum, we have investigatedCD14 expression in colonic tissue, to identify cell types likely to be activated by these products. : Colitis was induced reproducibly in BALB/c mice using oral 5% dextran sodium sulphate (DSS). This model allows the examination of CDI4 expression throughout the development of the inflammatory response. Mice exposed for four days to DSS developed diarrhea and then rectal bleeding on day 5 or6. Histological changes in the colon were assessed after 4,6 and 8 days of exposure to DSS. lmmunohistochemistry was performed using the avidinbiotin-peroxidase technique on serial sections to study the cell membrane expression of CDI4, and to identify cell types. Monoclonal antibody F4/80 and RB6 8C5 were used tO identify macrophages and neutrophils respectively. Immunohistochemical staining revealed the presence of CD14 on inflammatory macrophages and neutrophils in the inflamed colon. Infiltrating macrophages were strongly CD14 positive and were identified in the lamina propia and submucosa of colons isolated on day 6 and 8. Neutrophils, the first cells recruited to the acute colitis lesion (day 4), demonstrated variable CD14 expression. Newly arrived neutrophils, localised close to blood vessels, were more positive than neutrophils more distant from blood vessels in the mucosa or submucosa. Many neutrophils were CD14 negative, suggesting that the level of expression of CD 14 on neutrophils is only transiently upregulated or that the CD14 receptor is shed from the cell surface. By contrast, resident macrophages in uninflamed colonic mucosa were found to be CD14 negative and remained CD14 negative during the progression of coIonic inflammation. These findings suggest that (i) newly arrived inflammatory macrophages and neutrophils in inflamed colon may have a heightened response to bacterial products and that (ii) normal colonic macrophages differ from other tissue macrophages (alveolar, peritoneal, Kupffer ceils) in that they are CD14 negative and this may be an advantage in the LPS-rich intestinal environment.
GASTROENTEROLOGY, VOI. 108, No. 4
• DEPLETION OF NEUTROPHILS DEE~,EASES DISEASE SEVERITY AND MORTALITY IN A MOUSE MODEL OF ULCERATIVE COLITIS. A. Wozniak, *D.P. Sharma, E. Van de Pol, S.R. McColl, W.F. Doe. Div. of Clinical Sciences and *Div. of Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia. Neutrophlls are the primary'effector cells in many inflammatory diseases and are thought to contribute to tissue destruction via release of lytic enzymes and toxic free oxygen and nitrogen radicals. Although neutrophils are recruited in large numbers to inflamed colon in ulcerative colitis (UC)i their contribution to the mucosal damage has not been well characterised. To examine the role of neutrophlls in the pathogenesis of experimental colitis, we have studied the effect of selective in vivo neutrophil depletion on the development and severity of acute colitis in mice. Colitis was induced in BALB/c mice by supplementing drinking water with 5% dextran sodium sulphate (DSS) for nine days. The disease was assessed by monitoring diarrhoea, rectal bleeding, weight loss and mortality up to day 15. Histological changes in the colon were assessed after 4,6 and 8 days of exposure to DSS. lmmunohistochemistry was performed using the avidinbiotin-peroxidase technique and specific anti-neutrophil antibody, RB6 8C5. Mice were depleted of neutrophlls using antibody RB6 8C5. The control mice received an irrelevant antibody (anti-I~ galactosidase), GL 113. Depletion of neutrophils dramatically reduced rectal bleeding and the overall mortality caused by exposure to DSS. While 48% of mice treated with control antibody had developed rectal bleeding after six days of exposure to DSS, only 2% of neutrophil-depleted mice showed signs of bleeding: By day 9, 80% of control mice and 17% of mice in the neutrophil-depleted group had rectal bleeding. By contrast, diarrhoea was not affected by the anti-neutrophil antibody treatment. By day 7, 73% of control mice and 63% of neutrophildepleted mice had diarrhoea. Histological evidence of breaches in small blood vessel wall integrity and marked neutropbil extravasation was associated with increased severity of disease symptoms, including weight loss and resulted in a high mortality rate in the control group. This mucosal vessel damage was largely prevented by depletion of neutrophils. By day 15, only 20% of mice in the control group survived the nine day exposure to DSS while the survival rate in neutrophil-depleted mice was 75%. These fmdings demonstrate that neutrophils infiltrating inflamed colonic mucosa in acute colitis contribute to the severity of the disease and that this ~ correlates with damage to mucosal blood vessels, possibly resulting in gross bleeding. Neutrophil-mediated damage may be so severe that it prevents recovery from the disease induced acutely by DSS, as reflected in the high mortality rate.
ABDOMINAL PAIN IS A COMMON PRESENTATION OF GIARDIA LAMBLIA N CHILDREN AND ADOLESCENTS. J.A. Wriqht, J. Odom. F.A. Franklin, R. Figueroa. Ped Gastro/Nutrition and Ped Virology, Dept. Ped., U. AI. Birmingham and The Children's Hospital of AI., Birmingnam, AL Diarrhea(D) is felt to be the usual presentation of Giardia lamblia(G). Abdominal pain(AP) and nausea(N) and/or vomiting(V) are also associated with G. After several patients with AP, but without D were diagnosed with G, we retrospectively reviewed all patients referred to the Pediatric GI clinic with nonspecific AP, D, or V who were diagnosed with G and determined their symptoms and response to therapy. Between 6/91 and 6/94, G was diagnosed in 60 patients by an ELISA assay for a G antigen in a stool sample (TrendScientific, St. Paul, MN). We found a striking difference in symptoms at presentation between patients < 36 months(too) and those > 36 too. The older patients had an unexpected distribution of symptoms. For the 39 patients > 36 mo(3.5-16yr), AP was the most common symptom, present in 27(69%). D was present in 14(36%), while N/V Was present in 9(23%). Of the 27 with AP, 13(48%) had no other symptoms. 21(78%) of those with AP did not have D. 5(18%) of the patients with AP did not respond to therapy. Three of these had additional diagnosis which could explain their pain (GER, cystic fibrosis), and two were eventually diagnosed as having irritable bowel syndrome. All patients with AP and additional symptoms responded to therapy. For the 21 patients < 36 mo, 17(81%) had D. With therapy 16(94%) of the patients with D improved. The symptoms of G differ for children of different ages. IN older children and adolescents, abdominal pain, without diarrhea, is a frequent manifestation. G should be investigated in patients with chronic abdominal pare.
AGA ABSTRACTS
• DOES APPENDECTOMY REALLY PROTECT A G A I N S T ULCERATIVE COLITIS? B L Woods, E N Steinberg, C A Homung, R Vasudeva, C W Howden, Department of Medicine, University of South Carolina School of Medicine, Columbia, SC. Aims : This study was designed to examine the recent European claim (Rutgeerts et al., Gastroenterol 1994; 106: 1251-3) that appendectomy protects against the development of ulcerative colitis (UC). The influence of appendectomy and tonsillectomy (also removal of lymphoid tissue) on development of UC and Crohn's disease (CD) were studied. Methods : Patients with UC or CD attending out-patient clinics of two teaching hospitals were interviewed by telephone, or their charts were reviewed. Patients with hypertension served as controls. Patients and controls were asked about previous appendectomy and tonsillectomy and data were also collected on age, sex, race, other past medical and surgical history, smoking and alcohol use, 65 patients with UC, 51 with CD, and 1O3 controls were evaluated. Mean ages were 53.9, 42.5, and 55.4 respectively. Results : Appendectomy had been performed in 10/65 UC patients (15.4%), 8/51 CD patients (15.7%) and 10/103 controls (9.7%). Odds ratio (OR) for development of UC after appendectomy was 1.69 (95% CI = 0.60-4.74 ; P=0.27). OR for CD was 1.73 (95% CI = 0.57-5.19 ; P=0.19). OR for either UC or CD was 1.71 (95% CI = 0,70-4.27 ; P=0.19). ORs for development of UC, CD and either UC or CD after tonsillectomy were 0.71 (95% CI = 0.30-1.68 ; P=0.39), 1.07 (95% CI = 0.45-2.54 ; P=0.87) and 0.86 (95% CI = 0.43-1.73 ; P=0:65) i'espectively. Conclusions : The results of this US-based study do not support the recent observation that appendectomy protects against development of UC. In addition, appendectomy does not protect against CD. Tonsillectomy does not protect against development of UC or CD.
• INFLAMMATORY MACROPHAGES BUT NOT RESIDENT MACROPHAGES EXPRESS MEMBRANE-BOUND CD14, A RECEPTOR FOR LIPOPOLYSACCHARIDE, IN A MOUSE MODEL OF ULCERATIVE COLITIS. A. Wozniak, E. Van de Pol, W.F. Doe. Div. of Clinical Sciences, John Curiin School of Medical Research, Australian N~ational University, Canberra, ACT, Australia. CD14 is a receptor for LPS complexed with a soluble LPS-binding protein (LBP) and is found on the surface of monocytes, macmphages and neutrophlls and in a soluble form in serum. Recent findings suggest that other bacterial constituents may also bind and activate the CD14 receptor. Binding of LPS-LBP complexes to CD14 at nanomolar concentrations leads to cell activation and release of proinflammatory cytokines. Since large quantities of LPS and other bacterial products are present in the colon and terminal ileum, we have investigatedCD14 expression in colonic tissue, to identify cell types likely to be activated by these products. : Colitis was induced reproducibly in BALB/c mice using oral 5% dextran sodium sulphate (DSS). This model allows the examination of CDI4 expression throughout the development of the inflammatory response. Mice exposed for four days to DSS developed diarrhea and then rectal bleeding on day 5 or6. Histological changes in the colon were assessed after 4,6 and 8 days of exposure to DSS. lmmunohistochemistry was performed using the avidinbiotin-peroxidase technique on serial sections to study the cell membrane expression of CDI4, and to identify cell types. Monoclonal antibody F4/80 and RB6 8C5 were used tO identify macrophages and neutrophils respectively. Immunohistochemical staining revealed the presence of CD14 on inflammatory macrophages and neutrophils in the inflamed colon. Infiltrating macrophages were strongly CD14 positive and were identified in the lamina propia and submucosa of colons isolated on day 6 and 8. Neutrophils, the first cells recruited to the acute colitis lesion (day 4), demonstrated variable CD14 expression. Newly arrived neutrophils, localised close to blood vessels, were more positive than neutrophils more distant from blood vessels in the mucosa or submucosa. Many neutrophils were CD14 negative, suggesting that the level of expression of CD 14 on neutrophils is only transiently upregulated or that the CD14 receptor is shed from the cell surface. By contrast, resident macrophages in uninflamed colonic mucosa were found to be CD14 negative and remained CD14 negative during the progression of coIonic inflammation. These findings suggest that (i) newly arrived inflammatory macrophages and neutrophils in inflamed colon may have a heightened response to bacterial products and that (ii) normal colonic macrophages differ from other tissue macrophages (alveolar, peritoneal, Kupffer ceils) in that they are CD14 negative and this may be an advantage in the LPS-rich intestinal environment.
GASTROENTEROLOGY, VOI. 108, No. 4
• DEPLETION OF NEUTROPHILS DEE~,EASES DISEASE SEVERITY AND MORTALITY IN A MOUSE MODEL OF ULCERATIVE COLITIS. A. Wozniak, *D.P. Sharma, E. Van de Pol, S.R. McColl, W.F. Doe. Div. of Clinical Sciences and *Div. of Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia. Neutrophlls are the primary'effector cells in many inflammatory diseases and are thought to contribute to tissue destruction via release of lytic enzymes and toxic free oxygen and nitrogen radicals. Although neutrophils are recruited in large numbers to inflamed colon in ulcerative colitis (UC)i their contribution to the mucosal damage has not been well characterised. To examine the role of neutrophlls in the pathogenesis of experimental colitis, we have studied the effect of selective in vivo neutrophil depletion on the development and severity of acute colitis in mice. Colitis was induced in BALB/c mice by supplementing drinking water with 5% dextran sodium sulphate (DSS) for nine days. The disease was assessed by monitoring diarrhoea, rectal bleeding, weight loss and mortality up to day 15. Histological changes in the colon were assessed after 4,6 and 8 days of exposure to DSS. lmmunohistochemistry was performed using the avidinbiotin-peroxidase technique and specific anti-neutrophil antibody, RB6 8C5. Mice were depleted of neutrophlls using antibody RB6 8C5. The control mice received an irrelevant antibody (anti-I~ galactosidase), GL 113. Depletion of neutrophils dramatically reduced rectal bleeding and the overall mortality caused by exposure to DSS. While 48% of mice treated with control antibody had developed rectal bleeding after six days of exposure to DSS, only 2% of neutrophil-depleted mice showed signs of bleeding: By day 9, 80% of control mice and 17% of mice in the neutrophil-depleted group had rectal bleeding. By contrast, diarrhoea was not affected by the anti-neutrophil antibody treatment. By day 7, 73% of control mice and 63% of neutrophildepleted mice had diarrhoea. Histological evidence of breaches in small blood vessel wall integrity and marked neutropbil extravasation was associated with increased severity of disease symptoms, including weight loss and resulted in a high mortality rate in the control group. This mucosal vessel damage was largely prevented by depletion of neutrophils. By day 15, only 20% of mice in the control group survived the nine day exposure to DSS while the survival rate in neutrophil-depleted mice was 75%. These fmdings demonstrate that neutrophils infiltrating inflamed colonic mucosa in acute colitis contribute to the severity of the disease and that this ~ correlates with damage to mucosal blood vessels, possibly resulting in gross bleeding. Neutrophil-mediated damage may be so severe that it prevents recovery from the disease induced acutely by DSS, as reflected in the high mortality rate.
ABDOMINAL PAIN IS A COMMON PRESENTATION OF GIARDIA LAMBLIA N CHILDREN AND ADOLESCENTS. J.A. Wriqht, J. Odom. F.A. Franklin, R. Figueroa. Ped Gastro/Nutrition and Ped Virology, Dept. Ped., U. AI. Birmingham and The Children's Hospital of AI., Birmingnam, AL Diarrhea(D) is felt to be the usual presentation of Giardia lamblia(G). Abdominal pain(AP) and nausea(N) and/or vomiting(V) are also associated with G. After several patients with AP, but without D were diagnosed with G, we retrospectively reviewed all patients referred to the Pediatric GI clinic with nonspecific AP, D, or V who were diagnosed with G and determined their symptoms and response to therapy. Between 6/91 and 6/94, G was diagnosed in 60 patients by an ELISA assay for a G antigen in a stool sample (TrendScientific, St. Paul, MN). We found a striking difference in symptoms at presentation between patients < 36 months(too) and those > 36 too. The older patients had an unexpected distribution of symptoms. For the 39 patients > 36 mo(3.5-16yr), AP was the most common symptom, present in 27(69%). D was present in 14(36%), while N/V Was present in 9(23%). Of the 27 with AP, 13(48%) had no other symptoms. 21(78%) of those with AP did not have D. 5(18%) of the patients with AP did not respond to therapy. Three of these had additional diagnosis which could explain their pain (GER, cystic fibrosis), and two were eventually diagnosed as having irritable bowel syndrome. All patients with AP and additional symptoms responded to therapy. For the 21 patients < 36 mo, 17(81%) had D. With therapy 16(94%) of the patients with D improved. The symptoms of G differ for children of different ages. IN older children and adolescents, abdominal pain, without diarrhea, is a frequent manifestation. G should be investigated in patients with chronic abdominal pare.