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\(\textit {Hintergrund:}\) Die Befunde der bisherigen Untersuchungen legen nahe, dass die Angst vor dem Tod ein wichtiger Faktor bei der Entstehung psychischer Erkrankungen ist. Insbesondere die Terror-Management-Theorie geht davon aus, dass Menschen zwei verschiedene Strategien anwenden, um mit Todesangst umzugehen: (1) Sie versuchen, ihren Selbstwert zu steigern; (2) sie halten die Werte ihrer Kultur hoch. \(\textit {Patienten und Methoden:}\) Im Rahmen einer prospektiven Studie wurden 56 ambulante Psychotherapie-Patienten (29 Frauen, Alter 42,8 Jahre, SD 13,8) vornehmlich mit depressiven Störungen mittels Interview/Fragebögen u.a. zu Angst vor dem Tod (BOFRETTA) sowie Religiosität untersucht. \(\textit {Ergebnisse:}\) Die Angst vor dem Tod korrelierte signifikant mit der Schwere der psychischen Symptomatik (BDI), Neurotizismus (NEO-FFI) sowie dem Hochhalten kultureller Werte (LeBe). Erwartungsgemäß zeigte sich ein signifikanter negativer Zusammenhang von Selbstwert und Angst vor dem Tod. Dieser zeigte sich nicht bei Vergleichsvariablen wie Lebenssinn, Religiosität und Spiritualität. \(\textit {Diskussion und Schlussfolgerungen:}\) Die Angst vor dem Tod spielt bei der Entstehung und Aufrechterhaltung psychischer Probleme eine wesentliche Rolle. Ein wichtiger protektiver Faktor gegen diese scheint das Selbstwertgefühl zu sein. Es lässt sich vermuten, dass das Hochhalten kultureller Werte zwar ein unbewusster Versuch ist, gegen die Angst vor dem Tod (und die psychische Symptomatik) vorzugehen, dieser allerdings nicht wirksam ist. \(\textit {Background:}\) The findings of previous studies suggest that death anxiety is an important factor for the development of mental disorders. Especially, terror management theory assumes that human beings use 2 different strategies to prevent death anxiety: (1) they try to increase "self-worth"; (2) they uphold the values of their culture. \(\textit {Patients and Methods:}\) Within the framework of this prospective study, 56 outpatients under psychotherapy (29 females, age 42.8 years, SD 13.8), mainly with depressive disorders, were investigated by interviews/surveys concerning death anxiety (BOFRETTA) as well as religiosity, among other things. \(\textit {Results:}\) Death anxiety was significantly correlated with the severity of psychic symptomatology (BDI), neuroticism (NEO-FFI), and upholding of cultural values (LeBe). As expected, there was a significant negative relationship between self-worth and death anxiety. This was not observed regarding other parameters, such as sense of life, religiosity, and spirituality. \(\textit {Discussion and Conclusions:}\) Death anxiety seems to play an important role in the development and continuation of mental problems. An important protective factor seems to be self-worth. It is assumed that upholding of cultural values is an unconscious attempt to reduce death anxiety and mental symptomatology; however, this is not effective.

\(\textbf {Background:}\) Open-door policies in psychiatry are discussed as a means to improve the treatment of involuntarily committed patients in various aspects. Current research on open-door policies focuses mainly on objective effects, such as the number of coercive interventions or serious incidents. The aim of the present study was to investigate more subjective perceptions of different psychiatric inpatient settings with different door policies by analyzing ward atmosphere and patient satisfaction. \(\textbf {Methods:}\) Quantitative data on the ward atmosphere using the Essen Climate Evaluation Scale (EssenCES) and on patient satisfaction (ZUF-8) were obtained from involuntarily committed patients (\(\it n\) = 81) in three psychiatric hospitals with different ward settings and door policies (open, facultative locked, locked). Furthermore, qualitative interviews with each of 15 patients, nurses, and psychiatrists were conducted in one psychiatric hospital with a facultative locked ward comparing treatment in an open vs. a locked setting. \(\textbf {Results:}\) Involuntarily committed patients rated the EssenCES’ subscale "Experienced Safety" higher in an open setting compared with a facultative locked and a locked setting. The subscale "Therapeutic Hold" was rated higher in an open setting than a locked setting. Regarding the safety experienced from a mental health professionals’ perspective, the qualitative interviews further revealed advantages and disadvantages of door locking in specific situations, such as short-term de-escalation vs. increased tension. Patient satisfaction did not differ between the hospitals but correlated weakly with the EssenCES’ subscale "Therapeutic Hold". \(\textbf {Conclusion:}\) Important aspects of the ward atmosphere seem to be improved in an open vs. a locked setting, whereas patient satisfaction does not seem to be influenced by the door status in the specific population of patients under involuntary commitment. The ward atmosphere turned out to be more sensitive to differences between psychiatric inpatient settings with different door policies. It can contribute to a broader assessment by including subjective perceptions by those who are affected directly by involuntary commitments. Regarding patient satisfaction under involuntary commitment, further research is needed to clarify both the relevance of the concept and its appropriate measurement.

Background: Open-door policies in psychiatry are discussed as a means to improve the treatment of involuntarily committed patients in various aspects. Current research on open-door policies focuses mainly on objective effects, such as the number of coercive interventions or serious incidents. The aim of the present study was to investigate more subjective perceptions of different psychiatric inpatient settings with different door policies by analyzing ward atmosphere and patient satisfaction. Methods: Quantitative data on the ward atmosphere using the Essen Climate Evaluation Scale (EssenCES) and on patient satisfaction (ZUF-8) were obtained from involuntarily committed patients (n = 81) in three psychiatric hospitals with different ward settings and door policies (open, facultative locked, locked). Furthermore, qualitative interviews with each of 15 patients, nurses, and psychiatrists were conducted in one psychiatric hospital with a facultative locked ward comparing treatment in an open vs. a locked setting. Results: Involuntarily committed patients rated the EssenCES’ subscale “Experienced Safety” higher in an open setting compared with a facultative locked and a locked setting. The subscale “Therapeutic Hold” was rated higher in an open setting than a locked setting. Regarding the safety experienced from a mental health professionals’ perspective, the qualitative interviews further revealed advantages and disadvantages of door locking in specific situations, such as short-term de-escalation vs. increased tension. Patient satisfaction did not differ between the hospitals but correlated weakly with the EssenCES’ subscale “Therapeutic Hold.” Conclusion: Important aspects of the ward atmosphere seem to be improved in an open vs. a locked setting, whereas patient satisfaction does not seem to be influenced by the door status in the specific population of patients under involuntary commitment. The ward atmosphere turned out to be more sensitive to differences between psychiatric inpatient settings with different door policies. It can contribute to a broader assessment by including subjective perceptions by those who are affected directly by involuntary commitments. Regarding patient satisfaction under involuntary commitment, further research is needed to clarify both the relevance of the concept and its appropriate measurement.

Duisburg, Essen, Univ., Diss., 2007 Somatostatin ist ein im menschlichen Körper weit verbreitetes Hormon, das nahezu alle endo- und exokrinen Sekretionen hemmt. Es spielt ebenfalls eine wichtige Rolle als Inhibitor der Zellproliferation. Die unterschiedlichen Effekte von Somatostatin werden durch Bindung des Hormons an seine spezifischen Membranrezeptoren vermittelt. Bislang konnten fünf humane Somatostatin-Rezeptorsubtypen (sst1-sst5) identifiziert werden. Im Rahmen dieser Arbeit konnte die mRNA-Expression der fünf Somatostatin-Rezeptorsubtypen in der gesunden Nebenniere und Nebennierentumoren unterschiedlicher Ätiologien nachgewiesen werden. Während in der gesunden Nebenniere die Expression aller fünf ssts identifiziert wurde, zeigten die verschiedenen Nebennierentumoren ein sich jeweils von der gesunden Nebenniere unterscheidendes Expressionsmuster. Die unterschiedliche Expression könnte auf neue Aspekte in der Pathogenese dieser Tumoren deuten. Die differenzierte Expression könnte zudem die diagnostischen und therapeutischen Strategien in der Behandlung solcher Tumoren mit Einsatz spezifischer Analoga von Somatostatin in Abhängigkeit von der Tumorart und dem exprimierten Rezeptorsubtyp erweitern. In der Kultur vitaler Nebennierenzellen scheinen die verwendeten Somatostatin-Analoga im Rahmen einer Rückkopplung die Expression einzelner ssts zu regulieren. Der in in-vitro Experimenten demonstrierte hemmende Effekt von Somatostatin und SOM230 auf die Hormonsekretion von Phäochromozytomzellen macht einen Einsatz von Somatostatin bzw. SOM230 in der Therapie dieser Tumorentität denkbar. Zur genaueren Charakterisierung der molekularen Regulation wurden die bekannten Promotorregionen der einzelnen Somatostatin-Rezeptorsubtypgene bezüglich ihrer transkriptionellen Bedeutung in Nebennieren-Modellsystemen untersucht. Während in Nebennierenrinden-Zelllinien bekannte sst-Promotorsequenzen aktiv waren, lässt die Fehlende Aktivität in der Nebennierenmarkzelllinie auf alternative Promotoren schließen. Das Hormon Ghrelin ist an der Regulation von Appetit, endokriner Sekretion und auch der Zellproliferation beteiligt und interagiert mit der Hypothalamus-Hypophysen-Nebennieren-Achse. In den vorgelegten Untersuchungen konnte eine sehr starke Expression von Ghrelin in der Nebenniere sowohl auf RNA wie auch auf Protein-Ebene gezeigt werden, die höher als in den meisten zum Vergleich untersuchten Geweben war. Ein Einfluss der Nebenniere auf die Appetitregulation und den Stoffwechsel unter Vermittlung von Ghrelin erscheint somit denkbar. In Nebennierentumoren war eine signifikante Abnahme der Ghrelin-Expression zu beobachten, deren pathophysiologische Relevanz noch unklar ist.

Rationale: Respiratory tract infections are common in patients suffering from pulmonary fibrosis. The interplay between bacterial infection and fibrosis is poorly characterized. It is still unclear whether bacterial infections in IPF are merely a secondary complication in a high-risk patient group, or if they can also worsen the underlying fibrosis. Therefore, we here analyzed the effect of Gram-positive bacterial infection on fibrosis exacerbation in mice. Methods: Fibrosis progression in response to S. pneumoniae was examined in two different mouse models of pulmonary fibrosis. The first model consists of adenoviral vector delivery of active transforming growth factor- 1 (TGF1) gene into the lungs of mice to induce pulmonary fibrosis. The other mouse model consists of diphtheria toxin (DT) administration to transgenic SPC-DTR mice to cause repetitive alveolar type II epithelial cell injury and subsequent pulmonary fibrosis. As a second hit, mice with established lung fibrosis underwent pulmonary infection with the prototypic community-acquired lung pathogen Streptococcus pneumoniae (Spn). Results: We demonstrate that wild-type (WT) mice exposed to adenoviral vector delivery of active transforming growth factor-1 (TGF1) or transgenic SPC-DTR mice exposed to diphtheria toxin to induce pulmonary fibrosis developed progressive fibrosis following infection with Spn, without exhibiting impaired lung protective immunity against Spn. Antibiotic treatment abolished infection-induced fibrosis progression. The cytotoxin pneumolysin (Ply) of Spn caused this phenomenon in a TLR4-independent manner, as Spn lacking Ply (Spnply) failed to trigger progressive fibrogenesis, whereas purified recombinant Ply did. Progressive fibrogenesis was also observed in AdTGF1-exposed, Ply-challenged TLR4 KO mice. Increased apoptotic cell death of alveolar epithelial cells along with an attenuated intrapulmonary release of antifibrogenic prostaglandin E2 was found to underlie progressive fibrogenesis in Ply-challenged AdTGF1exposed mice. Importantly, vaccination of mice with the non-cytotoxic Ply derivative PdB substantially attenuated Ply-induced progression of lung fibrosis in AdTGF1 exposed mice. Conclusions: Our data unravel a novel mechanism by which infection with Spn through Ply release induces progression of established lung fibrosis, which can be attenuated by protein-based vaccination of mice.