1
April 2000 AGAA1359 60 80 ItiO "r"-------------, 100 120 140 improved. These findings support other research that suggests increased risk of Crohn s disease with improved early life conditions. 6187 PLATELET ACTIVATION IN PATIENTS WITH INFLAMMA- TORY BOWEL DISEASE. Silke Mortensen, Gerhard RogIer, Daniela Vogl, Juergen Schoelmerich, Tilo Andus, Mario Koksch, Dept of Internal Medicine I, Regen sburg, Germany; Dept of Internal Medicine I, Univ of Regensburg, Regensburg, Germany; Dept of Internal Medicine I, Leipzig, Germany. Background: Crohn's disease patients have an increased risk of thrombo- embolic diseases. This may be due to altered platelet function. Recently, we developed a whole blood flow cytometric assay for the quanti fication of the platelet activation marker P-selectin. In the present study we investi- gated platelet P-selectin expression in patients with inflammatory bowel disease to see whether there is a general risk associa ted with the diseas e or a specific risk during acute flares. Methods: Citrated blood samples were taken from 10 control patients and 17 patients with inflammatory bowel disease . Platelets were identified in whole blood using a phycoerythrin- labelled anti-fibrinogen receptor monoclonal antibody (mab). A fluoresce- in-isothiocya nate-conjugated mab was used for the quant ification of the P-selectin surface expression on non-stimulated and ADP-stimulated plate- lets. Results: Mean fluorescence intensity of anti-Pvselectin stained non- stimulated platelets in IBD patients were: 3.3 :!: 0.9 and in controls: 2.7 :!: 0.2. Mean fluorescence inten sity of ADP- stimulated platelets was 9.7 :!: 3.5 vs. 7.0 :!: 1.4 in the patient group compared to controls (p<0.05). Patients with C-reactive protein levels > 4 rng/l had significantly higher values (p<0.005) than patients with a CRP :s 4 mg/l (non-stimulated: 3.7 :!: 0,7 vs. 2.6 :!: 0.3 ; ADP : 12.6 :!: 4.8 vs. 7.6 :!: 3.3). A significant difference between patient group s was also obtained when stool frequency > 3 was used as indicator of disease activity. Patients in remission (stool fre- quency < 3, CRP < 4 rng/l) did not significantly differ from controls. Concl usion: Platele ts of patients with active inflammatory bowel disease are pre-activated and express higher levels of the activation marker P- selectin. Patients in remission do not differ from controls. During active disease platelets are systemically activated. lt61 .It i 1194( 194R Q 0 11 .. (]I lit Jt - 21 D ;rj III I -111 :II 40 50 6:) 'lO II 911 ------------------, 6186 IS THERE A BIRTH COHORT EFFECT FOR CROHN'S DIS- EASE? Daniell e L. Morris, David A. Leon, James Kyle, Scott M. Montgomery, Roy E. Pounder, Andrew 1. Wakefield , Royal Free and Univ Coll Med Sch, London , United Kingdom; London Sch of Hygiene & Tropical Medicine, London, United Kingdom; Univ of Aberde en Med Sch, Aberdeen, United Kingdom. Background: Birth cohort effects have been described for inflammatory bowel disease (lBD) in some countries (Sweden, Scotland) and for ulcer- ative colitis (UC) in others (England, Switzerland), but not for Crohn s disease alone. Aims: To look for specific birth coho rts at increased risk of later CD in a longitudinal study in Northeast Scotland. Methods: 855 patients with CD diagnosed 1955-1988 in Northeast Scotland. IO-year birth cohorts were used from 1893 to 1973. Indirect standardisation was used to account for the changing age distribution with time, to give an age- standardised cohort incidence ratio (SCIR). The age-specific incidence of all birth cohorts combined was the standard. Results: The highest incidence of CD was found in those born in the latest possible birth cohort for that age. The SCIR s shown below support this although only those cohorts born after 1943 show incidence risks greater than the weighted average . Discussion: Crohn s disease incidence increased with time especially in those born after World war II, when childhood material conditions had 6185 DOES THE RISING INCIDENCE OF CROHN'S DISEASE RE- FLECT IMPROVEMENT IN CHILDHOOD CIRCUMSTANCES? Danielle L. Morris, James Kyle, Scott M. Montgomery, Roy E. Pounder, Royal Free and Univ Coil Med Sch, London, United Kingdom; Univ of Aberdeen Med Sch, Aberdeen, United Kingdom. Background: Early environment and childhood infections may be impor- tant in Crohn s disease (CD) aetiology. Infant mortality is a proxy measure of these and is inversely associated with CD incidence in some countries. Aim: To assess the association of infant mortality rates (IMR) with CD incidence in different age groups in Northeast Scotland. Methods: All cases of CD (n= 856) in Northeast Scotland with onset between 1955 and 1988 were used with demograph ic records to create a dataset. Subjects were divided into < 15 yrs, 15-44 yrs, and > 44yrs. Linear regression was used to investigate relation ships between IMR in mean year of birth with age-specific CD incidence. Results: An inverse relatio nship is found in those with CD onset < 15 yrs, with a sharp increase in risk in those born > 1950. A similar rise is seen after 1950 in those age 15-44 yrs (below). In those with onset > 44 yrs (born < 1927) a linear relationship is seen. Conclusions: Changing conditions in early life may account for the in- creasing incidence of CD in this region. This is most marked for those born after WWII , following large improvements in material circumstances.

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April 2000 AGAA1359

60

80

ItiO "r"-------------,

100 +---......,..."----J~--_JL_----_1

120

140

improved. These findings support other research that suggests increasedrisk of Crohn s disease with improved early life conditions.

6187PLATELET ACTIVATION IN PATIENTS WITH INFLAMMA­TORY BOWEL DISEASE.Silke Mortensen, Gerhard RogIer, Daniela Vogl, Juergen Schoelmerich,Til o Andus, Mario Koksch, Dept of Internal Medi cine I, Regen sburg,Germany; Dept of Internal Medicine I, Univ of Regensburg, Regensburg,Germany; Dept of Internal Medicine I, Leipzig, Germany.

Background: Crohn' s disease patients have an increased risk of thromb o­embolic diseases . This may be due to altered platelet function. Recently,we developed a whole blood flow cytometric assay for the quanti fication ofthe platelet activation marker P-selectin. In the present study we investi­gated platelet P-selectin expression in patients with inflammatory boweldisease to see whether there is a general risk associa ted with the diseas e ora specific risk during acute flares. Methods: Citrated blood samples weretaken from 10 control patients and 17 patients with inflammatory boweldisease . Platelets were identified in whole blood using a phycoerythrin­labelled anti-fibrinogen receptor monoclonal antibody (mab). A fluoresce­in-isothiocya nate-conjugated mab was used for the quant ification of theP-selectin surface expre ssion on non-stimulated and ADP-stimulated plate­lets. Results: Mean fluorescence intensity of anti-Pvselectin stained non­stimulated platelets in IBD patients were: 3.3 :!: 0.9 and in controls: 2.7 :!:0.2. Mean fluorescence intensity of ADP-stimulated platelets was 9.7 :!: 3.5vs. 7.0 :!: 1.4 in the patient group compared to controls (p<0.05). Patientswith C-reactive protein levels > 4 rng/l had significantly higher values(p<0.005) than patients with a CRP :s 4 mg/l (non-stimulated: 3.7 :!: 0,7vs. 2.6 :!: 0.3 ; ADP : 12.6 :!: 4.8 vs. 7.6 :!: 3.3). A significant differencebetween patient group s was also obtained when stool frequency > 3 wasused as indica tor of disease activity . Patients in remission (stool fre­quency < 3, CRP < 4 rng/l) did not significantly differ from controls.Concl usion: Platele ts of patients with active inflammatory bowel diseaseare pre-activated and express higher levels of the activation marker P­selectin. Patient s in remission do not differ from controls. During activedisease platelets are systemically activated.

lt61.It

i 1194( 194RQ • IC~0 11 ..(]I lit

~Jt-~•21 D

;rjIII

I -111:II ~ 40 50 6:) 'lO II 911

------------------,

6186IS THERE A BIRTH COHORT EFFECT FOR CROHN'S DIS­EASE?Daniell e L. Morris, David A. Leon, James Kyle, Scott M. Montgomery,Roy E. Pounder, Andrew 1. Wakefield , Royal Free and Univ Coll Med Sch ,London , United Kingdom; London Sch of Hygiene & Tropical Medicine,London, United Kingdom; Univ of Aberde en Med Sch, Aberdeen, UnitedKingdom.

Background: Birth cohort effects have been described for inflammatorybowel disease (lBD) in some countries (Sweden, Scot land) and for ulcer­ative colitis (UC) in others (England, Switzerland), but not for Crohn sdisease alone. Aims: To look for specific birth coho rts at increased risk oflater CD in a longitud inal study in Northeast Scotland. Method s: 855patients with CD diagnosed 1955-1988 in Northeast Scotland. IO-year birthcohorts were used from 1893 to 1973. Indirect standardisation was used toaccount for the changing age distribution with time, to give an age­standardised cohort incidence ratio (SCIR). The age-specific incidence ofall birth cohorts combined was the standard. Results: The highest incidenceof CD was found in those born in the latest possible birth cohort for thatage. The SCIR s shown below support this although only those cohortsborn after 1943 show incidence risks greater than the weighted average .Discussion: Crohn s disease incidence increased with time espec ially inthose born after World war II, when childhood material conditio ns had

6185DOES THE RISING INCIDENCE OF CROHN'S DISEASE RE­FLECT IMPROVEMENT IN CHILDHOOD CIRCUMSTANCES?Danielle L. Morris, James Kyle, Scott M. Montgomery, Roy E. Pounder,Royal Free and Univ Coil Med Sch, London, United Kingdom; Univ ofAberdeen Med Sch, Aberdeen, United Kingdom.

Background: Early environment and childhood infections may be impor­tant in Crohn s disease (CD) aetiology. Infant mortality is a proxy measureof these and is inversely associated with CD incidence in some countries .Aim: To assess the association of infant mortali ty rates (IMR) with CDincidence in different age groups in Northeast Scotland. Methods: All casesof CD (n = 856) in Northeast Scotland with onset between 1955 and 1988were used with demograph ic records to create a dataset. Subjects weredivided into < 15 yrs, 15-44 yrs, and > 44yrs . Linear regression was usedto investigate relation ships between IMR in mean year of birth withage-specific CD incidence. Results: An inverse relatio nship is found inthose with CD onset < 15 yrs, with a sharp increase in risk in those born> 1950 . A similar rise is seen after 1950 in those age 15-44 yrs (below). Inthose with onset > 44 yrs (born < 1927) a linear relationship is seen.Conclusions: Changing conditions in ear ly life may account for the in­creasing incidence of CD in this region. This is most marked for those bornafter WWII , following large improvements in material circumstances .