Intestinal response to β-lactoglobulin in infants with cow's milk allergy
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A834 AGA ABSTRACTS GASTROENTEROLOGY, VoI. IOS, No. 4 • DIAGNOSISOF ILEAL CROHN'S DISEASE: A COMPARATIVESTUDY OF ILEOSCOPY VS. SMALL BOWEL MEAL WITH PNEUMOCOLON. J. Hewak. R. Farrow, C. Wright, S. Somers, R. Riddell, E.J. Irvine. MeMaster University, Hamilton, Ontario, Canada. Terminal ileal imaging is important for the diagnosis, extent and severity of Crohn's disease (CD). To evaluate the accuracy of imaging techniques to assess the terminal ileum, a retrospective review comparing small bowel meal with pneamocolon (SBMP) and colonoscopy/ileuscopy was performed. Between January, 1993 and May, 1994, 173 patients at MeMaster University Medical Centre had both SBMP and colonoscopy, The terminal ileal appearance was recorded in the colonoscopy report of 48 patients who comprised our study population. The mean age was 37 years (range 10 - 75) and 35 (73%) were female. Histology of the terminal ileum was available in 40 cases. SBMP radiographs or colonoseopy reports were reexamined by two radiologists or gastroenterologiats who independently scored each radiograph or colonoscopy report as definite CD, possible CD, other diagnosis or normal. The histology was reviewed in a blinded fashion by two G.I. pathologists. A gold standard diagnosis was determined for each patient by consensus of the investigators after compiling all available data: The gold standard diagnoses were CD in 14 patients, lymphoid nodular hyperpiasia (LNH) in 5 and normal in 29. The sensitivity and specificity of each imaging modality are listed below: Any abnormality Cr01~s disease LNH Suns. Spec. Suns. Spec. Suns. Spec. SBMP 86% 95% 100% 97% 40% 100% lleoseopy I 95% 86% 92% 100% 100%* 91% p < 0.01 Disagreement between SBMP and ileoseopy occurred in 5 .patients who were diagnosed to have CD or possible.CD by SBMP but had LNH or a normal exam at ileosc0py. Ileoseopy missed CD in one patient and over diagnosed LNH in 4. Conclusions: Ileoscopy appears to be superior for discriminating LNH from C D of the terminal ileum. Colonoscopy with ileoscopy should thus be performed to confirm isolated CD of the terminal ileum suggested by SBMP, prior to initiating therapy. A prospective study is needed to determine whether LNH detected by ileoscopy is indeed a false positve diagnosis. INTESTINAL RESPONSE TO ~-LACTOGLOBULIN IN INFANTS WITH COW'S MILK ALLERGY. M. Heyman, D. Sa'idi, O. Kheroua, G. Boudraa, P. Bylsma, R. Kerroucha, A. Chekroun, JA. Maragi, M. Touhami, .IF. Desjeux. Physiologic de la Nutrition, Universit6 d'Omn, Alg6rie, INSERM U290 Hrpital St Lazar±, Paris, France. Chronic diarrhea is the main digestive symptom in cow's milk allergy (CMA) in children. We tested the hypothesis that the bovine milk protein l~-lactoglobulin ([~-LG) may initiate a secretion at the human intestinal level. ~-LG or human ¢t-lactalbumin (h-et-LA, self antigen) was placed on the luminal surface of jejunal biopsies fi'om CMA infants, taken as part of the diagnosis procedure, mounted'in Uasing chambers, 2 days (Active CMA group, n=17} or 6 months (symptom-free group, n=6) after initiating a co~w'smilk free diet. On the same jejunal fragment we measured both short-circuit current lsc as;~in index of chloride secretion and protein transport using ]4C-~-LG or 14C-ct-LA. Degradation of t~-LG during transpor; was assessed by selective ~embrane ultrafiltration of serosal compartments. Results: 1) [~-LG absorption was greater in the Active CMA group (3315±323 ng/h.em 2) than in the!:~mptom-free group (1002e221 ng/h.em2). 2) Before addition of [~-LG, Isc was similar in both infant groups (-40 ttA/cm2). The mucosal addition of I~LG induced a significant rise in Isc up to 66 gA/cm2.in the Active CMA group only, while this stimulation was not observed in the ~ymptom-free group (33±6 IxA/cm2~! In the Active CMA group, h-a-LA failed to increase Isc. 3) 13-LG degradation during transepithelial transport was lower in Active CMA patients (77%) than in symptom-face patients (92%) 4) The electrical resistance of the biopsies was decreased in Active CMA group (18±2 f~.cm2) compared to the symptom-free group (31±7 ~.cm2) suggesting some alteration of the epithelial barrier. These results indicate that during the active phase of CMA, jejunal response to [~-LG challenge consist in an increase in chloride secretion and I~-LG absorption. This response may be specific to the bovine milk protein I~-LG as human a-LA did not stimulate chloride secretion. Both responses could explain the diarrhea observed in CMA and be secondary to a common mechanism depending on the activation of underlying sensitized immune cells. • ASPIRIN PROVOKES AN EXAGGERATED INCREASE IN THE LACTULOSE/MANNITOL PERMEABILITY INDEX IN FIRST- DEGREE RELATIVES OF CROHN'S PATIENTS. R.J. Hilsden, J. Meddings, L.R. Sutherland. GI Research Unit, University of Calgary, Calgary, Alberta. e have previously demonstrated that a :subsetof first-degree relatives o f Crohn's disease (CD) patients have an increased baseline intestinal permeability (IP). The purpose of this study was to determine if the detection of an ahnormality in IP in this group could be enhanced by pre-treatment with aspirin (ASA). Methods! Laetulose/mannitol permeability tests were administered before and after the ingestion of two 1.3 g doses of aspirin (at noon and 1 hr. before drinking the second test solution) in 12 healthy controls, 15 first-degree relatives, and 13 inactive (CDAI < 150) Crohn!s patients. The test solution (5 g lactu!ose, 2 g mannitol, 100 g sucrose in450 ml water) was administered at bedtime and urine was collected overnight for at least five hours in a container with 10% thymol in isopropanol as a preservative. The two tests were separated by 3 - 10 days. Urine sugar concentrations were measured by HPLC. Results are expressed as the ratio of the fractional excretion of lactulose to the fractional excretion of mannitol (L/M). Results: 1) 27% (95% CI, 8% - 55%) of relatives, 0% .(0% - 25%) o f Crohn's patients, and 8% (0% - 34%) of controls had an abnormal baseline L/M (> 0.022). 2) In those with a normal baseline L/M, 27% (6% - 6i%) of relatives; 23% (5% - 54%) of Crohn's patients and 0% (0% -29%)of controls had an abnormal increase after taking aspirin. 3) In total, 47% of relatives had either an abnormal baseline IP or abnormal increase post-ASA. Conclusions: 1) A subset of bealthy~ftrstdegree relatives of Croha's disease patients have abnormal baseline intestinal permeability, confirming previous restilts. 2) Relatives can be divided into three subgroups based on permeability testing: (I) normal iP, (II) abnormal baseline IP, (II~ exaggerated increase in IP in response to a damaging agent. First-degree relatives are known to be at the highest risk of developing eD. It is possible that those destined to develop CD may be categorized by one of these subgroups. IP testing may allow stratification of the risk of developing CD in relatives, though at present this is unproven. e GASTROSPIRILLUM-LIKE SPIRAL BACTERIA IN GASTRIC MUCOSAL BIOPSIES. N. Hil~enrat, E. Lamoureux, I. Weintrub, E. Alpert, M. Lichter, L. Alpert. Depts of Pathology and (Division of Gastroenterology) Medicine, Jewish General Hospital and McGill University, Montreal, Quebec, Canada. The presence of Helicobacter pylori in the stomach is highly associated with histological gastritis and peptic ulcer disease. Recent reports have suggested another spiral bacterium, Gastrospirillum hominis, as a less frequent gastric pathogen. Unusually long spiral bacteria, suggestive of G. hominis, were found in gastric biopsies from 4 patients during a 12 month period during which 1,042 upper endoscopies with biopsies were performed at the Jewish General Hospital, Montreal, Quebec. Among those 904 endoscopies in which H. pylori was actively saught histologically (Warthin-Starry stain was used when bacteria were not found on H+E-stained sections), H. pylori was found in 59% and G. hominis-like -spiral bacteria were found in 5 biopsies in 4 patients for a prevalence of 0.5%. These four patients presented with abdominal complaints and on endoscopy were found to have thickened gastric folds, antritis or peptic ulcers. Histologic gastritis was present in each patient. Serology for H.pylori was negative in three and positive in one. One patient's symptoms improved without therapy. One patient with dyspepsia was not treated. Two patients were treated with antibacterial therapy. One of these improved; no bacteria were documented on repeat biopsy. The other was coinfected with H. pylori on short term follow-up. This study suggests that G. hominis-like spiral bacteria may be a significant; though uncommon cause of gastric inflammation, that they can be distinguished from H. pylori on biopsy and that some patients infected with them may benefit from anti-H, pylori-antibiotic therapy.
Transcript of Intestinal response to β-lactoglobulin in infants with cow's milk allergy
A834 AGA ABSTRACTS GASTROENTEROLOGY, VoI. IOS, No. 4
• DIAGNOSIS OF ILEAL CROHN'S DISEASE: A COMPARATIVE STUDY OF ILEOSCOPY VS. SMALL BOWEL MEAL WITH PNEUMOCOLON. J. Hewak. R. Farrow, C. Wright, S. Somers, R. Riddell, E.J. Irvine. MeMaster University, Hamilton, Ontario, Canada.
Terminal ileal imaging is important for the diagnosis, extent and severity of Crohn's disease (CD). To evaluate the accuracy of imaging techniques to assess the terminal ileum, a retrospective review comparing small bowel meal with pneamocolon (SBMP) and colonoscopy/ileuscopy was performed. Between January, 1993 and May, 1994, 173 patients at MeMaster University Medical Centre had both SBMP and colonoscopy, The terminal ileal appearance was recorded in the colonoscopy report of 48 patients who comprised our study population. The mean age was 37 years (range 10 - 75) and 35 (73%) were female. Histology of the terminal ileum was available in 40 cases. SBMP radiographs or colonoseopy reports were reexamined by two radiologists or gastroenterologiats who independently scored each radiograph or colonoscopy report as definite CD, possible CD, other diagnosis or normal. The histology was reviewed in a blinded fashion by two G.I. pathologists. A gold standard diagnosis was determined for each patient by consensus of the investigators after compiling all available data: The gold standard diagnoses were CD in 14 patients, lymphoid nodular hyperpiasia (LNH) in 5 and normal in 29. The sensitivity and specificity of each imaging modality are listed below:
Any abnormality Cr01~s disease LNH
Suns. Spec. Suns. Spec. Suns. Spec.
SBMP 86% 9 5 % 100% 97% 40% 100%
lleoseopy I 95% 86% 92% 100% 100%* 91%
p < 0.01 Disagreement between SBMP and ileoseopy occurred in 5 .patients
who were diagnosed to have CD or possible.CD by SBMP but had LNH or a normal exam at ileosc0py. Ileoseopy missed CD in one patient and over diagnosed LNH in 4. Conclusions: Ileoscopy appears to be superior for discriminating LNH from C D of the terminal ileum. Colonoscopy with ileoscopy should thus be performed to confirm isolated CD of the terminal ileum suggested by SBMP, prior to initiating therapy. A prospective study is needed to determine whether LNH detected by ileoscopy is indeed a false positve diagnosis.
INTESTINAL RESPONSE TO ~-LACTOGLOBULIN IN INFANTS WITH COW'S MILK ALLERGY. M. Heyman, D. Sa'idi, O. Kheroua, G. Boudraa, P. Bylsma, R. Kerroucha, A. Chekroun, JA. Maragi, M. Touhami, .IF. Desjeux. Physiologic de la Nutrition, Universit6 d'Omn, Alg6rie, INSERM U290 Hrpital St Lazar±, Paris, France.
Chronic diarrhea is the main digestive symptom in cow's milk allergy (CMA) in children. We tested the hypothesis that the bovine milk protein l~-lactoglobulin ([~-LG) may initiate a secretion at the human intestinal level. ~-LG or human ¢t-lactalbumin (h-et-LA, self antigen) was placed on the luminal surface of jejunal biopsies fi'om CMA infants, taken as part of the diagnosis procedure, mounted'in Uasing chambers, 2 days (Active CMA group, n=17} or 6 months (symptom-free group, n=6) after initiating a co~w's milk free diet. On the same jejunal fragment we measured both short-circuit current lsc as;~in index of chloride secretion and protein transport using ]4C-~-LG or 14C-ct-LA. Degradation of t~-LG during transpor; was assessed by selective ~embrane ultrafiltration of serosal compartments.
Results: 1) [~-LG absorption was greater in the Active CMA group (3315±323 ng/h.em 2) than in the!:~mptom-free group (1002e221 ng/h.em2). 2) Before addition of [~-LG, Isc was similar in both infant groups (-40 ttA/cm2). The mucosal addition of I~LG induced a significant rise in Isc up to 66 gA/cm2.in the Active CMA group only, while this stimulation was not observed in the ~ymptom-free group (33±6 IxA/cm2~! In the Active CMA group, h - a - L A failed to increase Isc. 3) 13-LG degradation during transepithelial transport was lower in Active CMA patients (77%) than in symptom-face patients (92%) 4) The electrical resistance of the biopsies was decreased in Active CMA group (18±2 f~.cm 2) compared to the symptom-free group (31±7 ~.cm 2) suggesting some alteration of the epithelial barrier.
These results indicate that during the active phase of CMA, jejunal response to [~-LG challenge consist in an increase in chloride secretion and I~-LG absorption. This response may be specific to the bovine milk protein I~-LG as human a - L A did not stimulate chloride secretion. Both responses could explain the diarrhea observed in CMA and be secondary to a common mechanism depending on the activation of underlying sensitized immune cells.
• ASPIRIN PROVOKES AN EXAGGERATED INCREASE IN THE LACTULOSE/MANNITOL PERMEABILITY INDEX IN FIRST- DEGREE RELATIVES OF CROHN'S PATIENTS. R.J. Hilsden, J. Meddings, L.R. Sutherland. GI Research Unit, University of Calgary, Calgary, Alberta.
e have previously demonstrated that a :subset of first-degree relatives o f Crohn's disease (CD) patients have an increased baseline intestinal permeability (IP). The purpose of this study was to determine if the detection of an ahnormality in IP in this group could be enhanced by pre-treatment with aspirin (ASA). Methods! Laetulose/mannitol permeability tests were administered before and after the ingestion of two 1.3 g doses of aspirin (at noon and 1 hr. before drinking the second test solution) in 12 healthy controls, 15 first-degree relatives, and 13 inactive (CDAI < 150) Crohn!s patients. The test solution (5 g lactu!ose, 2 g mannitol, 100 g sucrose in450 ml water) was administered at bedtime and urine was collected overnight for at least five hours in a container with 10% thymol in isopropanol as a preservative. The two tests were separated by 3 - 10 days. Urine sugar concentrations were measured by HPLC. Results are expressed as the ratio of the fractional excretion of lactulose to the fractional excretion of mannitol (L/M). Results: 1) 27% (95% CI, 8% - 55%) of relatives, 0% .(0% - 25%) o f Crohn's patients, and 8% (0% - 34%) of controls had an abnormal baseline L/M (> 0.022). 2) In those with a normal baseline L/M, 27% (6% - 6i%) of relatives; 23% (5% - 54%) of Crohn's patients and 0% (0% -29%)of controls had an abnormal increase after taking aspirin. 3) In total, 47% of relatives had either an abnormal baseline IP or abnormal increase post-ASA. Conclusions: 1) A subset of bealthy~ftrst degree relatives of Croha's disease patients have abnormal baseline intestinal permeability, confirming previous restilts. 2) Relatives can be divided into three subgroups based on permeability testing: (I) normal iP, (II) abnormal baseline IP, (II~ exaggerated increase in IP in response to a damaging agent. First-degree relatives are known to be at the highest risk of developing eD. It is possible that those destined to develop CD may be categorized by one of these subgroups. IP testing may allow stratification of the risk of developing CD in relatives, though at present this is unproven.
e G A S T R O S P I R I L L U M - L I K E S P I R A L B A C T E R I A IN G A S T R I C M U C O S A L B I O P S I E S . N. H i l ~ e n r a t , E. Lamoureux , I. We in t rub , E. Alper t , M. Lichter , L. Alpert . Dep ts o f P a t h o l o g y and (D iv i s i on o f G a s t r o e n t e r o l o g y ) Medic ine , Jewish Genera l Hospi ta l and McGi l l Univers i ty , Montreal, Quebec, Canada.
The presence o f Helicobacter pylori in the s tomach is h igh ly assoc ia ted wi th h is to logical gastri t is and peptic u lcer d i sease . R e c e n t r epor t s have s u g g e s t e d ano the r sp i ra l bacter ium, Gastrospirillum hominis, as a less f requent gastric pathogen. Unusua l l y long spiral bacteria, sugges t ive o f G. hominis, were found in gastric biopsies f rom 4 patients dur ing a 12 mon th period dur ing which 1,042 upper endoscopies with b iops ies were p e r f o r m e d at the Jewish Genera l Hospi ta l , Montreal, Quebec. A m o n g those 904 endoscopies in which H. pylori was actively saugh t his tological ly (Warthin-Starry stain was used when bac te r i a were no t found on H+E-s t a in ed sect ions) , H. pylori was found in 59% and G. hominis-like
-spiral bacteria were found in 5 b iops ies in 4 pat ients for a p reva lence o f 0 .5%. These four pa t ien ts p resen ted wi th a b d o m i n a l compla in t s and on endoscopy were found to have th ickened gastr ic folds, antrit is or peptic ulcers . His to logic gastritis was p re sen t in each patient. Serology for H.pylori was negat ive in three and posit ive i n one. One patient 's s y m p to m s improved without therapy. One patient with dyspepsia was not treated. Two pat ients were treated with antibacterial therapy. One of these improved; no bacteria were documented on repeat biopsy. The other was coinfected with H. pylori on short te rm fol low-up. This s tudy sugges t s that G. hominis-like spiral bacter ia m a y be a s igni f icant ; t hough u n c o m m o n cause o f gastr ic in f lammat ion , that they can be d i s t inguished f rom H. pylori on biopsy and that some patients infected with them m a y benefit from anti-H, pylori-antibiotic therapy.
