ddc:600

Die Transplantatvaskulopathie (TVP) stellt im Langzeitverlauf noch immer die Haupttodesursache herztransplantierter Patienten dar und limitiert somit deren Langzeitüberleben entscheidend. Bisher ist die Pathogenese dieser besonderen Form der Atherosklerose weitgehend ungeklärt und die Diagnostik nur mit invasiven Methoden möglich. Da sich inzwischen die Hinweise für eine Beteiligung zirkulierender vaskulärer Progenitoren bei der Entwicklung der klassischen Atherosklerose mehren, untersuchten wir die Rolle endothelialer und glattmuskulärer Progenitorzellen bei der Entwicklung der Transplantatvaskulopathie. In diese prospektive Studie wurden 207 herztransplantierte Patienten eingeschlossen. Die zirkulierenden Progenitoren wurden durchflusszytometrisch als % der mononukleären Zellen in Blutproben aus dem peripheren Blut bestimmt. Dabei wurden die endothelialen Progenitoren als CD34/KDR doppeltpositiv, die glattmuskulären Progenitoren als CD34/PDGFR-ß doppeltpositiv identifiziert. Die Schwere der TVP wurde zum Einen angiographisch im Rahmen einer Koronarangiographie und zum Anderen bei einer Subpopulation von 40 Patienten auch mittels intravaskulärem Ultraschall (IVUS) und der Methode der „virtuellen Histologie“ ermittelt. Für die mittels IVUS untersuchten Patienten ergab sich eine gute Korrelation zwischen der Prävalenz der angiographisch diagnostizierten TVP und den erhobenen IVUS Daten. Des Weiteren zeigte sich im Rahmen der virtuellen Histologie, dass sich die Zusammensetzung der Plaquekomponenten im zeitlichen Verlauf nach Herztransplantation von fibrotischen zugunsten von kalkhaltigen Anteilen verändert. Bezüglich der Progenitoren ließ sich kein signifikanter Zusammenhang zwischen der Entwicklung einer TVP und dem Nachweis von endothelialen Vorläuferzellen zeigen. Allerdings fiel eine deutlich höhere Anzahl glattmuskulärer Progenitoren bei Patienten mit angiographisch nachweisbarer TVP als bei Patienten ohne TVP auf. Damit deuten die Ergebnisse dieser Studie erstmals darauf hin, dass glattmuskuläre Progenitorzellen an der Entwicklung der TVP beteiligt sein könnten.

In the presented thesis, matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry was used for the proteomic analysis of gastric cancer tissue samples, with the aims of 1) identifying proteins that predict disease outcome of patients with intestinal-type gastric cancer after surgical resection, and 2) generating a proteomic classifier that determines HER2-status in order to aid in therapy decision with regard to trastuzumab (Herceptin) administration. In the first study, a seven-protein signature was found to be associated with an unfavorable overall survival independent of major clinical covariates after analyzing 63 intestinal-type primary resected gastric cancer samples by MALDI imaging. Of these seven proteins, three could be identified as CRIP1, HNP-1, and S100-A6, and validated immunohistochemically on tissue microarrays of an independent validation cohort (n=118). While HNP-1 and S100-A6 were found to further subdivide early (UICC-I) and late stage (UICC-II-III) patients into different prognostic groups, CRIP1, a protein previously unknown in gastric cancer, was confirmed as a novel and independent prognostic factor for all patients in the validation cohort. The protein pattern described here serves as a new independent indicator of patient survival complementing the previously known clinical parameters in terms of prognostic relevance. In the second study, we hypothesized that MALDI imaging mass spectrometry may be useful for generating a classifier that may determine HER2-status in gastric cancer. This assumption was based on previous results where HER2-status could be reliably predicted in breast cancer patients. Here, 59 gastric cryo tissue samples were analyzed by MALDI imaging and the obtained proteomic profiles were used to create HER2 prediction models using different classification algorithms. Astonishingly, the breast cancer proteomic classifier from the previous study was able to correctly predict HER2-status in gastric cancers with a sensitivity of 65% and a specificity of 92%. In order to create a universal classifier for HER2-status, breast and non-breast cancer samples were combined, which increased sensitivity to 78%; specificity was 88%. This study provides evidence that HER2-status can be identified on a proteomic level across different cancer types suggesting that HER2 overexpression may constitute a widely spread molecular event independent of the tumor entity.

The core aim of nursing practice is to improve or maintain the person’s well-being and quality of life. The use of standardized classifications and terminologies can contribute to this aim by facilitating intra- and inter-professional communication. Therefore, it is important to explore approaches that enhance common use of the current standard classifications of all health-care professions. The overall objective of this doctoral thesis was to investigate whether the International Classification of Functioning, Disability and Health (ICF) is a practicable and useful classification for nurses - using spinal-cord injury (SCI) nursing as an example. This doctoral thesis comprises the research, results and conclusions of two original studies published in the nursing journal “Journal of Advanced Nursing” first authored by the doctoral candidate. The objective of the first study was to identify the conceptual and practical relationships between the inter-professional ICF and the nursing-specific NANDA-I Taxonomy II for nursing diagnoses. The specific research questions were: (1) What are the commonalities and differences between the conceptional frameworks and assessment principles of the ICF and the NANDA-I Taxonomy II? and (2) Can the two classifications serve as a combined approach in SCI nursing practice? The discussion of the conceptual and practical relationships between the ICF and the NANDA-I Taxonomy II is based on (1) the most recently published descriptions of both classifications and (2) the illustration of a SCI-specific case example presenting the combined use of both classifications. The objective of the second study was to analyse the extent to which the intervention goals of nurses when caring for persons with SCI can be expressed in the standardized language of the ICF. The specific research questions were: (1) Which problems, resources and aspects of the environment of persons with SCI relevant to nurses can be translated into the ICF language? and (2) Which problems, resources and aspects of the environment relevant to nurses are still missing in the ICF? The method used to answer these questions was a worldwide Delphi Survey with SCI nurses. The results of this doctoral thesis shed light on the use of the ICF in nursing practice. First, I discuss the commonalities and differences between the ICF and the NANDA-I Taxonomy II that should be taken into account when implementing both 10 classifications in nursing practice. Important clinical requirements that are exclusive to nursing can be met with the NANDA-I Taxonomy II. The application of the ICF helps nurses communicate abbreviated nursing issues with other health professionals in a common language. A combined application of the ICF and the NANDA-I Taxonomy II is valuable, and they can complement each other to enhance the quality of clinical teamwork and nursing practice. Second, I provide a list of patients’ problems, patients’ resources or aspects of their environment treated by SCI nurses that might be introduced in nursing practice for a comprehensive standardized documentation and for a better exchange of information in a common language with other health professionals. Third, I show the strengths and weaknesses of the ICF when used in nursing care specific to SCI and provide evidence for the update and future revisions of the ICF. For example, I propose to add two qualifiers, one for “Risk for” and one for “Resource for” to the existing qualifier scale. Several recommendations for future research are based on the results of this doctoral thesis. First, there is a need to continue exploring the simultaneous use of the ICF and NANDA-I Taxonomy II. A complete linking of both classifications could reveal their commonalities and differences in a more detailed way and identify all missing elements in the ICF for nursing purposes. Second, the list of patients’ problems, patients’ resources or aspects of their environment treated by SCI nurses should be validated in different nursing settings (e.g. acute hospital care, rehabilitative care and community care). This list should also be compared with the existing Comprehensive ICF Core Sets for SCI in the early post-acute context and long-term context. Third, the personal factors identified should be taken into account when developing the ICF component Personal Factors.

Schönheit und Ästhetik des menschlichen Gesichts werden stark von der Ohrmuschel bestimmt. Obwohl eine abstehendes Ohr per se direkt keinen Krankheitswert hat, können u.a. Hänseleien krankhafte Zustände generieren. Zur operativen Korrektur abstehender Ohren gibt es mittlerweile eine breites Spektrum an Methoden. In der vorliegenden Arbeit sollte nun per retrospektivem Studiendesign die Nachttechnik nach Mustardé vor allem bezüglich der gesunheitsbezogenen Lebensqualität und der Komplikationsrate evaluiert werden. Zusammenfassend lässt sich hierbei ein sehr positiver Effekt bezüglich der Lebensqualität bei gleichzeitig vertretbarer Komplikationsrate konstatieren.