The gastric hormone ghrelin, its expression in the upper gastrointestinal tract and its integration in known hormonal regulatory systems

Hintergrund und Ziele: Das Hormon Ghrelin, welches hauptsächlich im Magen, jedoch auch in anderen Geweben gebildet wird, wurde erstmalig 1999 von Kojima et al. entdeckt und spielt eine große Rolle in der Energiehomöostase des Körpers. Hauptsächlich wurde Ghrelin als serologischer Marker für Erkrankungen des Magen-Darm-Trakts untersucht. Über die Verteilung und Expression in krankhaft verändertem Gewebe ist wenig bekannt. Ziel dieser Arbeit war es, morphologische Veränderungen des Ghrelinzellbildes in entzündlichem und metaplastischem Gewebe des oberen Gastrointestinaltrakts herauszuarbeiten und mit gesundem Gewebe zu vergleichen. Ein besonderes Augenmerk wurde auf die Autoimmungastritis gelegt. Darüber hinaus sollte der Zusammenhang zwischen Ghrelin und Gastrin untersucht werden. Methoden: Verschiedene Gewebearten des oberen Gastrointestinaltrakts (Ösophagus, Magencorpus, Magenantrum, Duodenum, Pankreas, Refluxösophagitis, Barrett-Mucosa, Pankreatische Metaplasie, Autoimmungastritis, Hp-Gastritis, Gastrale Metaplasie) wurden immunhistochemisch bzw. mittels Doppelimmunfluoreszenzfärbung teils mit konventioneller Mikroskopie, teils mit konfokaler Lasermikroskopie untersucht. Weiterhin wurden das Serumghrelin und Serumgastrin von Autoimmungastritispatienten gemessen und mit Werten von gesunden Probanden verglichen. Ergebnisse: Ghrelinzellen konnten in normalem Gewebe wie erwartet bevorzugt im Magen detektiert werden. Das Ghrelinzellbild ändert sich in entzündlichen und metaplastischen Geweben deutlich. Hier entstehen teilweise Ghrelinkonglomerate und eine lineare Progression der Ghrelinzellen. Dies betrifft vor allem die Autoimmungastritis. Diskrete Veränderungen in diese Richtung zeigten sich auch in der Hp-Gastritis. Weiterhin wurde auf humanen Ghrelinzellen erstmalig der Gastrinrezeptor nachgewiesen, was bislang nur im Rattenmodell gezeigt wurde. Als serologischer Marker wurde Ghrelin bei Autoimmungastritispatienten, bei denen eine Hypergastrinämie vorherrscht, untersucht. Der Spiegel des aktiven Ghrelins war signifikant erniedrigt und korrelierte damit negativ zu den Gastrinwerten. Schlussfolgerungen: Mit dieser Studie ist es gelungen, ein differenziertes Modell der Ghrelinexpression in entzündlichen und metaplastischen Geweben des oberen Gastrointestinaltrakts zu zeichnen. Zudem konnte aufgrund des gefundenen Gastrinrezeptors auf humanen Ghrelinzellen, der starken Expression des Rezeptors bei der Autoimmungastritis, des Mitreagierens im Rahmen der endokrinen Zellknötchen und durch Blutanalysen Hinweise gesammelt werden, dass Ghrelin durch Gastrin wesentlich beeinflusst wird. Somit ermöglicht diese Arbeit eine Erweiterung und bessere Definition des komplex gesteuerten gastralen Hormonsystems.Objective: Ghrelin is a hormone which is mainly produced in the stomach but also in other tissues. It was detected in 1999 by Kojima et al. and plays an important role in the energy homeostasis of the body. So far, Ghrelin has been examined mainly as a serological marker for diseases of the gastrointestinal tract. Little is known about the distribution and expression of ghrelin cells in pathologically modified tissues. The aim of this study was to examine morphologic changes in inflammatory and metaplastic tissue and to compare it to normal tissue of the upper gastrointestinal tract. Special attention was payed to the autoimmune gastritis. Furthermore, the interaction of ghrelin and gastrin was investigated. Methods: Different types of tissue of the upper gastrointestinal tract (esophagus, gastric corpus, gastric antrum, duodenum, pancreas, reflux esophagitis, barrett mucosa, pancreatic metaplasia, autoimmune gastritis, Hp gastritis, gastral metaplasia) were examined using classic immunohistochemistry and double immunofluorescence. Conventional microscopy and confocal laser microscopy were applied. Moreover, serum ghrelin and serum gastrin levels of patients with autoimmune gastritis were measured and compared to levels of healthy subjects. Results: As expected, Ghrelin cells were detected in all normal tissues. The picture of ghrelin cells changes in inflammatory and metaplastic tissues. Conglomerates and linear progression occur especially concerning the autoimmune gastritis. The Hp gastritis also showed such modifications. Furthermore, the gastrin receptor, which had only been found on ghrelin cells of the rat, could be detected on human ghrelin cells. As a serological marker, ghrelin was examined in patients with autoimmune gastritis showing hypergastrinemia. Serum levels of active ghrelin were significantly lower and were negatively correlated with gastrin levels. Conclusions: This study shows a differentiated model of ghrelin expression in inflammatory and metaplastic tissues of the upper gastrointestinal tract. Moreover, evidences that ghrelin is essentially influenced by gastrin were found by the detected gastrin receptor on human ghrelin cells, the strong expression of this receptor in autoimmune gastritis, the reaction within the endocrine cell conglomerates and by serum assays. Therefore, this study is an enhancement and allows a better defini-tion of the complexly controlled gastric hormone system

Comparative evaluation of different medication safety measures for the emergency department: physicians’ usage and acceptance of training, poster, checklist and computerized decision support

Background Although usage and acceptance are important factors for a successful implementation of clinical decision support systems for medication, most studies only concentrate on their design and outcome. Our objective was to comparatively investigate a set of traditional medication safety measures such as medication safety training for physicians, paper-based posters and checklists concerning potential medication problems versus the additional benefit of a computer-assisted medication check. We concentrated on usage, acceptance and suitability of such interventions in a busy emergency department (ED) of a 749 bed acute tertiary care hospital. Methods A retrospective, qualitative evaluation study was conducted using a field observation and a questionnaire-based survey. Six physicians were observed while treating 20 patient cases; the questionnaire, based on the Technology Acceptance Model 2 (TAM2), has been answered by nine ED physicians. Results During field observations, we did not observe direct use of any of the implemented interventions for medication safety (paper-based and electronic). Questionnaire results indicated that the electronic medication safety check was the most frequently used intervention, followed by checklist and posters. However, despite their positive attitude, physicians most often stated that they use the interventions in only up to ten percent for subjectively “critical” orders. Main reasons behind the low usage were deficits in ease-of-use and fit to the workflow. The intention to use the interventions was rather high after overcoming these barriers. Conclusions Methodologically, the study contributes to Technology Acceptance Model (TAM) research in an ED setting and confirms TAM2 as a helpful diagnostic tool in identifying barriers for a successful implementation of medication safety interventions. In our case, identified barriers explaining the low utilization of the implemented medication safety interventions - despite their positive reception - include deficits in accessibility, briefing for the physicians about the interventions, ease-of-use and compatibility to the working environment