Inflammatory bowel disease (IBD), characterized by chronic gastrointestinal inflammation, represents a significant childhood chronic disease. In this thesis, a case ascertainment definition of paediatric-onset IBD was validated using administrative data and developed the Ontario Crohn’s and Colitis Cohort (OCCC). The epidemiology of paediatric IBD in Ontario was described, demonstrating that Ontario has one of the highest worldwide incidence rates. Statistically significant increases in incidence were noted in 0-4 year olds (5.0%/year, p=0.03) and 5-9 year olds (7.6%/year, p<0.0001), but not in other age groups. Lower income children were more likely to be hospitalized at least once (hazard ratio (HR) 1.17, 95% confidence intervals (CI) 1.05-1.30) or visit the ED (HR 1.21, 95% CI 1.09-1.35) and had more IBD-related physician visits (odds ratio (OR) 3.73, 95% CI 1.05-13.27). Lower income children with Crohn's disease (CD) (not ulcerative colitis [UC]) were more likely to undergo intra-abdominal surgery within 3 years of diagnosis (OR 1.22, 95% CI 1.01-1.49), especially if diagnosed after 2000 (OR 1.79, 95% CI 1.27-2.53). Finally, changes in health services utilization and surgical rates were described, as were changes in specialist care provision and immunomodulator use in children with IBD between 1994-2007. The changes to care included increased outpatient care provided by paediatric gastroenterologists, and increased immunomodulator use. Children diagnosed with CD, but not UC, in recent years had lower surgical rates. In CD patients, intra-abdominal surgical rates within three years of diagnosis decreased from 18.8% in children diagnosed in 1994-1997 to 13.6% in those diagnosed in 2001-2004 (P = 0.035). When stratified by age at diagnosis, this decrease was significant in children diagnosed ≥10 years old (OR 0.67, 95% CI 0.48-0.93). The OCCC will continue to be used to investigate the epidemiology and burden of paediatric IBD and to improve the care received by children with IBD in Ontario.

Bakgrund: En kronisk oförutsägbar sjukdom som Crohns sjukdom framkallar fysisk, psykologisk och social stress. Sjukdomen påverkar vardagen, försämrar livskvalitet och skapar oro. För att bedriva personcentrerad vård krävs insikt i hur denna oro upplevs. Syfte: Syftet med studien var att belysa sjukdomsrelaterad oro hos personer med Crohns sjukdom. Metod: Åtta kvinnor och fyra män mellan 30 och 64 år som skattat sin sjukdomsrelaterade oro som hög eller mycket hög identifierades. Intervjuer genomfördes och analyserades med kvalitativ innehållsanalys. Resultat: Analysen genererade tre kategorier: (1) Oro för sjukdomen i sig, (2) känslor runt oron, (3) samt hantering av oron. Sjukdomens oförutsägbarhet samt nedsatt funktion till följd av trötthet och bristande kontroll över tarmfunktionen var de mest framträdande orsakerna till oro. Oron skapade känslor av stress, skuld och besvikelse. Deltagarna uttryckte önskemål att få prata om och synliggöra oron men hade också funnit egna sätt att hantera denna. Slutsats: Det finns ett kvarstående behov av att ventilera och få förståelse för sjukdomsrelaterad oro, även efter många års sjukdom. Personer med Crohns sjukdom måste få prata om sin oro, vara en aktiv partner i vården och tillsammans med vårdgivaren finna sätt att hantera oron så att denna kan lindras. / Background: A chronic, unpredictable disease as Crohn's disease provides physical, psychological and social stress. The disease affects everyday life, impairs quality of life and create worries. To conduct person-centered care requires insight into how this worry is experienced. Objective: To explore disease-related worries in persons with Crohn´s disease. Method: Eight women and four men between 30 and 64 who estimated their disease-related worries high or very high were identified. Interviews were conducted and analyzed with content analysis. Results: The analysis generated three categories: (1) Worries about the disease itself, (2) feelings around the worries, (3) management of the worries. The unpredictable course of the disease and the impaired function due to fatigue and lack of control of bowel function were the most prominent causes of worries. The worries created feelings of stress, guilt and disappointment. The participants expressed the wish to talk about and make the worries visible but had also found their own ways to handle it. Conclusion: There is a persistent need to vent and get an understanding of disease-related worries, even after many years of disease. Persons with Crohn's disease need to talk about their worries, be an active partner in healthcare and together with the health-care providers find ways to handle the worries so it can be relieved.

No description available.

Zurzeit existieren keine validen Biomarker, welche die Krankheitsaktivität oder das Rezidiv-Risiko von chronisch-entzündlichen Darmerkrankungen objektivierbar machen. Im Rahmen dieser Arbeit wurden neue Biomarker des Immunmonitorings auf ihren Nutzen bei der Beurteilung der Krankheitsaktivität von Patienten mit chronisch-entzündlichen Darmerkrankungen (CED) untersucht. Hierzu wurde bei 98 Patienten mit CED, nach positivem Votum der Ethikkommission, die intrazelluläre ATP-Konzentration der CD4+-Zellen gemessen, um diese mit der Krankheitsaktivität der Patienten in Bezug zu setzen. Die Patientendaten wurden zuvor mithilfe von standardisierten Fragebögen erhoben, um daraufhin die Krankheitsaktivitätsindices CDAI, HBI und SCCAI aus den klinischen Daten zu ermitteln. Es wurde keine signifikante Korrelation zwischen der ATP-Konzentrationen und der Krankheitsaktivität der Patienten festgestellt. Dies führte zu der Schlussfolgerung, dass Einzelmessungen der intrazellulären ATP-Konzentration von Lymphozyten nicht die Krankheitsaktivität von Patienten mit chronisch-entzündlichen Darmerkrankungen widerspiegeln. Ein signifikanter Unterschied der intrazellulären ATP-Konzentration CD4+-Zellen wurde allerdings zwischen Patienten mit und ohne Infliximab-Therapie nachgewiesen. Die Patienten, die unter einer Infliximab-Therapie standen, hatten signifikant niedrigere intrazelluläre ATP-Konzentrationen der Lymphozyten (p<0,01, Mann-Whitney-U). Dieses Ergebnis verdeutlicht, dass Infliximab als TNF-α-Blocker die Immunantwort bzw. die Aktivität von Lymphozyten inhibiert. Mithilfe der intrazellulären ATP-Konzentration wäre somit evtl. ein Werkzeug gegeben, um die Effektivität der Inhibierung der lymphozytären Immunreaktion durch TNF-α-Blocker zu kontrollieren. Weiterhin wurde bei 99 CED-Patienten die Anzahl regulatorischer T-Zellen im peripheren Blut bestimmt. Hierfür wurden die Zellen mithilfe von CD4-, CD25-, CD127- und FoxP3-Antikörpern angefärbt und mittels der FACS-Analytik quantifiziert. Anschließend wurde die so ermittelte Anzahl regulatorischer T-Zellen (CD4+CD25highCD127-FoxP3+-Zellen) mit der Krankheitsaktivität der Patienten korreliert. Auch dabei wurde keine signifikante Korrelation nachgewiesen. Bei der Unterteilung der Patienten in Gruppen mit erhöhter und erniedrigter Krankheitsaktivität deutete sich ein Unterschied bezüglich der Anzahl regulatorischer T-Zellen an, der jedoch nicht signifikant war (p=0,073, Mann-Whitney-U-Test). Diese Ergebnisse führten zu der Annahme, dass sich die durchflusszytometrisch quantifizierte Anzahl regulatorischer T-Zellen ebenfalls nicht als Surrogatmarker für die Krankheitsaktivität von Patienten mit chronisch-entzündlichen Darmerkrankungen eignet. Zudem wurde postuliert, dass die Quantifizierung von Tregs keine Hilfe bei der Unterscheidung zwischen den beiden Erkrankungen Morbus Crohn und Colitis ulcerosa liefern kann. Der tendenzielle Unterschied in der Anzahl von Tregs zwischen Patienten mit niedriger und erhöhter Krankheitsaktivität zeigt jedoch, dass regulatorische T-Zellen bei der Pathogenese von chronisch-entzündlichen Darmerkrankungen eine Rolle zu spielen scheinen. Allerdings deutet sich auch eine Abhängigkeit von weiteren pathogenen Faktoren in der komplexen Ätiologie von chronisch-entzündlichen Darmerkrankungen an. Bei 35 der CED-Patienten wurde zusätzlich eine weitere Methode zur Quantifizierung regulatorischer T-Zellen angewendet. Hierbei handelte es sich um einen DNA-Methylierungsassay, welcher die regulatorischen T-Zellen anhand einer spezifischen Demethylierungsregion der DNA (TSDR) ermittelt. Diese TSDR ist bei den Tregs demethyliert, während sie bei allen anderen Zellen des Blutes methyliert ist. Die Ergebnisse dieses Assays korrelierten jedoch nicht mit der Krankheitsaktivität der Patienten und korrelierten auch nicht mit den Ergebnissen für die Anzahl regulatorischer T-Zellen aus der FACS-Analytik. Diese Tatsache könnte zum einen darauf beruhen, dass in der FACS-Analytik im Gegensatz zum DNA-Methylierungsassay auch aktivierte T-Effektorzellen quantifiziert werden, welche nur transient FoxP3 exprimieren. Zum anderen werden mittels des DNA-Methylierungsassays auch CD8+FoxP3+-Zellen quantifiziert, welche keine oder geringe regulatorischen Eigenschaften besitzen und in der Durchflusszytometrie nicht quantifiziert werden. Zudem könnte eine fehlende Korrelation zwischen den Ergebnissen der beiden Verfahren auch daran liegen, dass sich die quantifizierten Tregs aus der Durchflusszytometrie auf die Gesamtheit der CD4+-Zellen beziehen, während sich die Tregs des DNA-Methylierungsassays auf die gesamten DNA-haltigen Zellen des Vollblutes beziehen. Zur besseren Vergleichbarkeit könnte in zukünftigen Studien ein Quotient aus Tregs und CD4+-Zellen gebildet werden. Zusammenfassend hat sich im Rahmen dieser Arbeit gezeigt, dass sich weder mithilfe der intrazellulären ATP-Konzentrationen von Lymphozyten noch der Anzahl regulatorischer T-Zellen eine Aussage bezüglich der Krankheitsaktivität oder des Rezidivrisikos von CED-Patienten treffen lässt. Da die chronisch-entzündlichen Darmerkrankungen derzeit nicht heilbar sind, werden weitere Surrogatmarker zum Objektivieren der Krankheitsaktivität benötigt, um Krankheitsrezidiven zeitnah entgegenwirken zu können.

The objectives of our study were to determine the potential of 1H MRS in detecting (1) early colonic inflammation, (2) effects of various fatty acids on normal colon and (3) their effects on IBD. Sprague dawley rat fed with 2% carrageenan was used as a model of IBD. Flaxseed oil served as ω-3, corn oil as ω-6 and beef tallow as saturated fatty acid sources. Control group animals were fed 5% corn oil, whereas, those in high-fat diet groups received an additional 7% of the respective fatty acids. After 2 weeks, 1H MRS and histology were conducted on excised colonic mucosa. Statistical classification strategy (SCS) used for analyzing 1H MRS data achieved an accuracy of 82 % in stage 1, 90-100% in stage 2 and 96-100% in stage 3. This implies that 1H MRS is a sensitive tool to diagnose early IBD and the effects of dietary fat on IBD.

Inflammatory bowel disease (IBD), comprises Crohn’s disease (CD) and ulcerative colitis (UC), and is a chronic relapsing inflammation of gastrointestinal tract without any known cause or cure. Currently, it is accepted that IBD is a result of a dysfunctional immune response to commensal bacteria in a genetically susceptible host, and that environmental factors can trigger the onset or reactivation of the disease. This thesis considers the possibility of a specific pathogenic agent as well as an imbalance in the composition of the normal microflora in the pathogenesis of IBD. Gut biopsy tissues were taken from a population-based case-control tissue bank held at the University of Manitoba. Automated ribosomal intergenic spacer analysis (ARISA) and terminal restriction fragment length polymorphisms (T-RFLP) were employed to assess the diversity of gut microbiota. The phylogenetic, virulence and biochemical characteristics of Escherichia coli isolated from IBD biopsies were examined using multi-locus sequence typing (MLST), DNA microarray technology and API 20E system. Utilizing ARISA and T-RFLP, a remarkable increase in the order of unclassified Clostridia was detected in inflamed tissues, particularly in CD patients (P < 0.05). Moreover, species richness and diversity were the highest in non-inflamed IBD biopsies. Culture-based quantification detected a significantly higher number of E. coli in IBD tissues (P < 0.05). Phylogenetic analysis revealed the tendency of E. coli isolated from IBD patients to be grouped into separate clonal clusters based on their allelic profiles (P = 0.02). A link was detected between uropathogenic E. coli (UPEC) CFT073 and strains isolated from IBD, with regards to gene distribution and virulence, using microarray technology. Amino acid substitutions N91S and S99N in FimH, the adhesive subunit of E. coli type I fimbria, were significantly associated to IBD (P < 0.05). This study demonstrated an increase in the microbial diversity of non-inflamed IBD tissues and suggested a recruitment phase of bacterial adherence and colonization, before the inflammation sets in. Furthermore, E. coli isolated from IBD tissues were distinct from commensal strains in both clonal and virulence characteristics and shared remarkable traits with extraintestinal pathogenic E. coli. Features involved in bacterial adhesion to epithelial cells may hold the key to E. coli pathogenesis in IBD.

Human alkaline phosphatase (ALP) comprises four isozymes, viz liver/bone/ kidney or tissue unspecific (AP), intestinal (LAP), placental (PLAP) and germ cell or PLAP-like alkaline phosphatase, with their main expression in specific tissues as indicated by their names. The isozymes are coded by different genes, but they are closely related, with more than 50% amino acid sequence homologies. Their biological function is unclear. In certain malignant and benign diseases, serum elevations of one or more of the isozymes occur, which is of diagnostic importance. In this study, the special expression of the intestinal isozyme in human tissues and sera, in normal as well as in pathological conditions, has been investigated by use of isozyme specific monoclonal antibodies. Monoclonal antibodies against the AP, IAP and PLAP isozymes were prepared, and specific assays developed, based on these monoclonal antibodies and the catalytic activity of the isozymes. By use of these assays the basal levels of all three isozymes were examined in selected normal organs. The isozymes were found to be expressed in measurable amounts in all the examined organs. IAP was immunohistochemically localized to the epithelial cells of membranes lining the ducts and tubules of the kidney, liver, pancreas and small intestine. Normal human serum contained all three isozymes. The AP isozyme constituted about 90% of the total ALP activity, the IAP isozyme less than 10% and the PLAP isozyme about 1%. Considerable interindividual variations of the serum IAP activity were observed. The serum activities of the IAP isozyme were related to the individual ABO blood group and secretor status. Non-secretors had low levels of IAP activity amounting to about one tenth of the activity in sera from blood group B or 0 secretors, while blood group A secretors had serum IAP activities in the same order as non-secretors. High individual day to day variations were observed. Fat absorption caused serum IAP to increase significantly for all persons, but it was rapidly cleared from the blood. We found that the release of IAP into the blood was linked to lipid absorption, but removal from the blood was not linked to lipoprotein clearance. Certain tumors of the testis expressed elevated levels of all three ALP isozymes. The highest activitiy of LAP was observed in one yolk sac tumor, in agreement with the endodermal origin of this tumor. In seminoma tissue the AP and PLAP isozymes were significantly, and IAP moderately elevated. Cirrhosis of the liver caused significantly increased serum levels of IAP besides the AP isozyme. In inflammatory diseases of the small intestine, normal serum IAP activities were observed. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 1992, härtill 7 uppsatser.</p> / digitalisering@umu

La maladie de Crohn et la rectocolite hémorragique font partie des maladies inflammatoires chroniques de l'intestin (MICI). Le principal objectif des traitements anti-inflammatoires est de favoriser la délivrance du principe actif localement, spécifiquement sur les zones enflammées et de limiter les effets indésirables. Ainsi, plusieurs systèmes à libération colonique de molécules actives ont été développés. Parmi eux, les pellets présentent de nombreux avantages par rapport aux formes solides unitaires conventionnelles. Dans un premier temps, des pellets comptant une substance anti-inflammatoire naturelle et nutritive, la rutine, ont été développés. L'intérêt de cette molécule est de réduire considérablement les effets secondaires qui constituent un véritable problème dans les traitements actuels des MICI. Les pellets ont été enrobé avec les polysaccharides naturels se dégradant avec la flore colonique. Les études in vitro ont démontré une libération minimale du principe actif au niveau de l'estomac et du petit intestin. Par contre, une libération rapide et totale a été observée lors de l'exposition des pellets dans les conditions du milieu colonique. Les résultats des tests in vivo ont démontré que la rutine a atténué considérablement l'inflammation au niveau de colon et les pellets enrobés ont été aussi efficaces que les pellets d'acide 5-aminosalicylique (5-ASA) commercialisés. L'administration orale de rutine via les pellets enrobés et préparés avec le chitosan semble être une approche prometteuse, permettant la libération du principe actif au niveau des zones enflammées, pour le traitement des MICI tout en réduisant les effets secondaires. Le deuxième but de notre travail était d'élucider l'impact du chitosan, un polymère mucoadhésif, sur l'efficacité thérapeutique. Les pellets de 5-ASA ont été préparés à partir de cellulose microcristalline avec ou sans chitosan. Un enrobage constitué d'un polymère pH dépendant,1' Eudragit® FS, a ensuite été réalisé autour du noyau. Les tests de dissolution ont montré que le principe actif n'était pas libéré du pellet après 2 h en milieu acide. En revanche,la libération était rapide dans un milieu simulant l'environnement colonique. Les tests ex vivo avec les pellets contenant le chitosan ont montré des propriétés mucoadhésives importantes qui ont été confirmées par la concentration élevée du métabolite de 5-ASA dans les tissus coloniques des rats. De plus, nous avons a démontré que les pellets permettaient d'atténuer de façon significative l'inflammation du côlon. Ainsi, les pellets bioadhésifs enrobés possèdent des propriétés bénéfiques supplémentaires pour la libération du 5-ASA au niveau du côlon par rapport à des formes multidoses commercialisées pour le traitement des MICI. / Crohn's disease and ulcerative colitis are two related but distinct chronic inflammatory disorders of gastrointestinal tract (GIT), commonly denoted as inflammatory bowel disease(IBD). The main goal of the anti-inflammatory treatment of this disorder is to achieve maximal drug concentration in inflamed area and reduce systemic adverse effects. For this purpose several colon-spécifie drug delivery systems have been investigated. In addition, the design of pellets as oral drug delivery systems may provide many advantages over single unit preparations and thus improve patient compliance. It is well known that most existing treatments of IBD are associated with significant side effects and for this reason the formulation with a " food like " composition was designed. In the first part of our study, therapeutic efficiency of rutin/chitosan pellets with coatings based on natural polysaccharides degraded by colonie microbiota compared to commercialized 5-aminosalicylic acid (5-ASA) pellets was investigated. Release profiles ofcoated pellets showed a minimal drug release in simulated stomach and small intestine following by rapid drug release upon exposure to the colonie fluid. The results from in vivo testing showed that rutin attenuated efficiently inflammation in the colon and coated pellets were as effective as 5-ASA pellets in mitigating experimental colitis. The studies demonstrated that rutin administration via chitosan core coated pellets seems to be apromising approach for colon-specific delivery since they could interact easily with the mucin layer and deliver drug especially to the inflamed colonie area to relieve symptoms of IBD omitting side effects related to conventional treatment. The second objective of this thesis was to explore the impact of additional mucoadhesive polymer chitosan in the pellets core on the therapeutic efficiency. For this purpose, 5-ASA loaded pellets were produced by extrusion/spheronisation method and subsequently coated with pH-sensitive polymer Eudragit® FS. No drug release at pH 1.2within 2 h, and release as intended in the simulated distal ileum and colon was observed. Chitosan-core pellets showed efficient mucoadhesive properties in ex vivo bioadhesion testing which were also confirmed by increased concentration of 5-ASA metabolite in the colonie tissues in rats. The pellets were tested in preexisting colitis and the results revealed significant attenuation of the colonie inflammation. We can conclude, that bioadhesive chitosan-corepellets showed additional beneficial properties for colonie 5-ASA delivery in the treatment of IBD over marketed dosage formulation.

Background: Inflammatory bowel disease (IBD) includes Crohn´s disease (CD) and ulcerative colitis (UK). The diseases are chronic and have a pattern of relapses interspersed with relatively symptom-free periods. Common symptoms during relapse are diarrhea, abdominal pain and weight loss. Since you have IBD for life it is important to find ways to relate to and cope with the disease. In that process a nurse can be of great help. Aim: The purpose of this literature review was to increase the understanding of how adult patients with inflammatory bowel disease experience their daily lives.   Method: The method used was a literature review. A literature search was performed in two separate databases which resulted in eleven examined and analyzed articles on the subject.  Results: After the analyze of the articles three different themes emerged: Limitations in daily life, Self-image and self-esteem and finally Self-care and strategies. Several individuals felt limited one way or the other in their daily life. They also described how their self-esteem was affected. Some positive changes due to the disease were also described. For example some changed their exercise and food habits for the better. Discussion: The results are discussed through the perspective of Antonovsky’s (1991/2005) salutogenic view and were connected to how the SOC (Sense of Coherence) was affected. The importance of relatives’ support and self-care was also discussed.

The objectives of our study were to determine the potential of 1H MRS in detecting (1) early colonic inflammation, (2) effects of various fatty acids on normal colon and (3) their effects on IBD. Sprague dawley rat fed with 2% carrageenan was used as a model of IBD. Flaxseed oil served as ω-3, corn oil as ω-6 and beef tallow as saturated fatty acid sources. Control group animals were fed 5% corn oil, whereas, those in high-fat diet groups received an additional 7% of the respective fatty acids. After 2 weeks, 1H MRS and histology were conducted on excised colonic mucosa. Statistical classification strategy (SCS) used for analyzing 1H MRS data achieved an accuracy of 82 % in stage 1, 90-100% in stage 2 and 96-100% in stage 3. This implies that 1H MRS is a sensitive tool to diagnose early IBD and the effects of dietary fat on IBD.