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Thesis (Doctoral)--Københavns universitet, 2005. / Includes bibliographical references.

Nowadays exists large amount of data which characterizes environment on base of different parametres. Due to existence of such large amount of data which is difficult to understand and comprehensively visualize, it is necessary to find tools for their proper visualization. The main goal of this thesis is present current environment in place of residence and show possible influence of environmental factors on health. For achieving the goal it was necessary to obtain individual sets of data and prepare them for each analysis and also for their presentation. In thesis there are described various aspects of environment in the area of Příbram region. Also in text is described in detail spatial determined medical data. Thesis contains O2PLS analysis which will create regression model for thyroid function parameters. Output of whole thesis is creating a web application that clearly presents input data (environmental and medical), geostatical and 02PLS analysis. Due to this work has been developed procedure how to prepare a analyze different type of data and also created detailed describtion of presentation results. Till now has not been proven what aspects can affect thyroid function. Many diseases are affected by the environment. This thesis focuses on influence of environment on thyroid function. Main...

Die vorliegende Dissertation befasst sich mit der Diagnostik und Therapie des primären Hyperaldesteronismus und im speziellen mit der selektiven Nebennierenvenenkatheteruntersuchung (NNVK). Hierfür wurden alle Patienten die innerhalb des Zeitraums von 2002-2017 am Universitätsklinikum Leipzig eine NNVK Untersuchung erhalten haben nachbeobachtet und der Therapieerfolg beurteilt. Zudem wurden systematisch klinische und präklinische Daten der Patienten analysiert um Rückschlüsse auf diagnostische Abläufe, den Stellenwert der NNVK Untersuchungen und Verbesserungsmöglichkeiten in der Patientenversorgung für Patienten mit einem primären Hyperaldosteronismus zu beurteilen.:Inhaltsverzeichnis 1. Einleitung 1 1.1. Pathophysiologie 1 1.2. Ätiologie 4 1.3. Epidemiologie 5 1.4. Diagnostik 6 1.4.1. Aldosteron-Renin-Quotient 7 1.4.1.1. Testbedingungen für ARQ 8 1.4.2. Bestätigungstest 9 1.4.3. Bildgebung 9 1.4.4. Selektive Nebennierenvenenkatheter-Untersuchung 10 1.4.4.1. Kontroverse zum NNVK 13 1.4.5. Orthostasetest 15 1.4.6. PET-CT Untersuchungen 16 1.5. Therapie 16 1.5.1. Kriterien für den Therapieerfolg 17 1.6. Komplikationen 18 2. Aufgabenstellung 19 3. Patienten und Methoden 20 3.1. Patienten vor NNVK-Untersuchung 21 3.2. Patienten in der Nachbeobachtung 22 3.3. Methoden 23 4. Ergebnisse 24 4.1. Eingangsdiagnostik 24 4.1.1. Fallerfassung 24 4.1.2. ARQ 25 4.1.3. Bestätigungstest 26 4.1.4. Bildgebung 26 4.1.5. Orthostasetest 27 4.2. Auswertung der NNVK-Untersuchung 28 4.2.1. Erfolgsquote und angewandter Selektionsindex 28 4.2.2. Angewandter Lateralisationsindex 30 4.2.3. Kongruenz von Bildgebung und NNVK 30 4.2.4. Therapieentscheidung 31 4.2.5. Komplikationen 32 4.2.6. Strahlenbelastung 33 4.3. Outcome der operativ behandelten Patienten 35 4.3.1. Blutdruck 37 4.3.2. Blutdruckmedikation 38 4.3.3. Kardiovaskuläre Ereignisse 39 4.3.4. Niedrigster gemessener Kaliumwert 40 4.3.5. ARQ 40 4.4. Outcome der konservativ behandelten Patienten 41 4.4.1. Blutdruck 41 4.4.2. Blutdruckmedikation 43 4.4.3. Kardiovaskuläre Ereignisse 43 4.4.4. Niedrigster gemessener Kaliumwert 44 4.4.5. ARQ 44 4.5. Vergleich Outcome Operativ vs. Konservativ 45 4.5.1. Blutdruck 45 4.5.2. Blutdruckmedikation 46 4.5.3. Niedrigster gemessener Kalium Wert 47 4.6. Besondere Patientengruppen 48 5. Diskussion 49 5.1. Diagnostischer Ablauf 49 5.2. Divergenz zwischen Bildgebung und NNVK-Ergebnis 50 5.3. Erfolgsquote des NNVK 51 5.4. Komplikationsrate des NNVK 51 5.5. Strahlenbelastung 52 5.6. Therapieentscheidung 53 5.7. Outcome 55 5.8. Limitationen 60 6. Zusammenfassung 62 Literaturverzeichnis 66 Anlagen 77

The adrenal glands are two major endocrine organs responsible for multiple physiological processes, including the stress response, modulating the immune system and metabolism. The adrenal is composed of an outer cortex and an inner medulla with distinct developmental origin and function. While tissue-specific stem/progenitor populations of the adrenal cortex have been widely identified and characterised, the presence of a functional stem/progenitor population in the medulla is unclear. Establishing cell hierarchy of the adrenal medulla essential to understand normal homeostasis, disease pathogenesis and establishing regenerative medicine strategies, therefore the identification of a stem/progenitor population would provide an important starting point for further basic and translational studies. Cell composition of the adrenal medulla includes three main cell types: chromaffin cells, which secrete catecholamines, neurons, which stimulate catecholamine production, and a third cell type with an unspecified “support” function called sustentacular cells. Using transcriptomics and genetic approaches in mouse, I established that a population of sustentacular cells express the stem/progenitor marker SOX2. These cells are present throughout life and have a developmental origin congruent with the rest of the gland. Through genetic lineage-tracing using the Sox2CreERT2 strain, I demonstrate that SOX2+ cells are an expanding population, capable of giving rise to the catecholamine-producing chromaffin cells, consistent with a stem cell role in vivo. I further demonstrate the self-renewal potential of SOX2+ cells through in vitro isolation and expansion, using a Sox2eGFP mouse line. Analysis of SOX2+ cells in physiological organ challenge suggests potential involvement of these cells in the response to perturbation of normal homeostasis. Through analysis of FFPE sections of human adrenals, I confirm the presence of SOX2+ cells in the normal adult organ, as well as in pheochromocytomas. Taken together, these data support the identification of a previously undescribed stem cell population in the mammalian adrenal medulla and confirm its functional relevance.

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