@article{AlbertWeissenbergerVarrallyayRaslanetal.2012,
  author    = {Albert-Weißenberger, Christiane and V{\´a}rrallyay, Csan{\´a}d and Raslan, Furat and Kleinschnitz, Christoph and Sir{\´e}n, Anna-Leena},
  title     = {An experimental protocol for mimicking pathomechanisms of traumatic brain injury in mice},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75368},
  year      = {2012},
  abstract  = {Traumatic brain injury (TBI) is a result of an outside force causing immediate mechanical disruption of brain tissue and delayed pathogenic events. In order to examine injury processes associated with TBI, a number of rodent models to induce brain trauma have been described. However, none of these models covers the entire spectrum of events that might occur in TBI. Here we provide a thorough methodological description of a straightforward closed head weight drop mouse model to assess brain injuries close to the clinical conditions of human TBI.},
  subject      = {Medizin},
  language  = {en}
}
@phdthesis{Aumann2018,
  author    = {Aumann, Ralf},
  title     = {Vorkommen und Expression des opcA Gens in Meningokokkenst{\"a}mmen von Erkrankten und asymptomatischen Tr{\"a}gern},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157278},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {Das Opc-Protein ist ein Außenmembranprotein von Meningokokken, das {\"u}ber extrazellul{\"a}re Matrixproteine mit Integrinen der Wirtszelle interagiert. Opc ist in Menschen immunogen und induziert bakterizide Antik{\"o}rper. Das Opc-Protein wurde daher als aussichtsreicher Impfstoff-Kandidat angesehen, da es außerdem relativ gut konserviert ist. Allerdings wird das Opc-Protein nicht von allen Meningokokkenst{\"a}mmen exprimiert. Einerseits fehlt das opc-Gen in einigen klonalen Komplexen (z.B. ST-8, ST-11, ST-53), andererseits ist die Opc-Expression nicht konstitutiv wegen einer phasenvariablen Transkription, die auf einem Poly-Cytidin-Bereich im Promotor des opc-Gens beruht. In dieser Arbeit wurde die Pr{\"a}senz des opc-Gens und die Opc-Expression in zwei großen Sammlungen deutscher Meningokokkenisolate von invasiven Erkrankungen (n=1141) und gesunden Tr{\"a}gern (n=792) untersucht. Das opc-Gen war bei 71\% der invasiven und 77\% der Tr{\"a}gerst{\"a}mme nachweisbar. Der gr{\"o}ßte Teil der opc-Gen negativen St{\"a}mme geh{\"o}rte zu den klonalen Komplexen ST-8, ST-11, ST-213, ST-231, ST-334 und ST-53. Der Anteil opc-positiver St{\"a}mme, die Opc in vitro exprimieren, war bei den invasiven St{\"a}mmen kleiner als bei den Tr{\"a}gerst{\"a}mmen (13\% vs. 29\%, p<0,001, Chi-square-Test). Der gr{\"o}ßere Anteil Opc-exprimierender Tr{\"a}gerst{\"a}mme ist u.a. am ehesten mit der {\"U}berrepr{\"a}sentation von wenig pathogenen klonalen Komplexen (ST-23, ST-35, ST-198) mit einer hohen Opc-Expressionsrate zu erkl{\"a}ren. 24 von den 176 invasiven St{\"a}mmen mit einer Anzahl von 11 - 14 Cs in der Promotor-Region, die die Opc-Expression beg{\"u}nstigt, zeigten weder im ELISA noch im Westernblot eine Opc-Expression. Bei 14 dieser 24 St{\"a}mme wurde als Ursache ein phasenvariabler, intragenischer Poly-Adenin-Bereich identifiziert, der zu einer Leserasterverschiebung f{\"u}hrte. Die Vermutung mehrerer Autoren, dass die Opc-Expression mit dem klinischen Bild der Meningitis verkn{\"u}pft ist, konnte mit der hier genutzten großen Stammsammlung nicht best{\"a}tigt werden. Invasive St{\"a}mme, die das Opc-Protein exprimierten, wurden genauso h{\"a}ufig von Patienten mit dem klinischen Bild der Meningitis isoliert wie St{\"a}mme, die das Opc-Protein nicht exprimierten (46\% vs. 47\%, Chi-square-Test: p<0,9). Allerdings gibt es eine starke Assoziation der Gegenwart des opc-Gens mit dem klinischen Merkmal Meningitis. Dieser Befund gibt Anlass zu der Hypothese, dass in vitro und in vivo Expression von Opc sich unterscheiden. Zusammenfassend l{\"a}sst sich festhalten, dass das Opc-Protein nur in 19,8\% aller Isolate (invasive und Tr{\"a}gerst{\"a}mme zusammengenommen) exprimiert wurde. Es zeigte sich eine Tendenz zu h{\"a}ufigerer Opc-Expression in apathogenen Tr{\"a}gerisolaten. Das Vorhandensein des opc-Gens, nicht aber die in vitro Expression konnten mit dem klinischen Merkmal Meningitis assoziiert werden. Zus{\"a}tzlich wurde ein weiterer Mechanismus der intragenischen Phasenvariation beschrieben.},
  subject      = {Neisseria meningitidis},
  language  = {de}
}
@article{BeckerSchmidtkeStoeberetal.1994,
  author    = {Becker, T. and Schmidtke, A. and St{\"o}ber, Gerald and Franzek, E. and Teichmann, E. and Hofmann, E.},
  title     = {Hyperintense Marklagerl{\"a}sionen bei psychiatrischen Patienten: r{\"a}umliche Verteilung und psychopathologische Symptome},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-78288},
  year      = {1994},
  abstract  = {In einem Kollektiv von 130 MR-tomographisch untersuchten psychiatrischen Patienten (axiale T2-SE-Sequenz) wurden Zahl und r{\"a}umliche Verteilung von hyperintensen Marklagerl{\"a}sionen ("white matter lesions"; WM L) erfaßt und die Ventricle-to-brain-Ratio (VBR) bestimmt. Eine Konfigurationsfrequenzanalyse auf der Grundlage der r{\"a}umlichen WMLVerteilung erlaubte die Abgrenzung von vier Patientengruppen: 1. keine WML (n = 35), 2. WML rechts frontotemporal (n = 23), 3. WML bifrontal (n = 12), 4. WML ubiquit{\"a}r (n = 16). Die w{\"a}hrend 3 Jahren beobachteten psychopathologischen Symptome dieser Patienten wurden retrospektiv nach dem AMDP-Systemdokumentiert. In der Gruppe mit ubiquit{\"a}ren WML {\"u}berwogen organisch-psychopathologische Ttems, die VER war gr{\"o}ßer als in den anderen Gruppen (ANOVA;p < 0,001). Die r{\"a}umliche W M L- Verteilung erkl{\"a}rte 10,24 \% der Gesamtvarianz psychopathologischer M erkmalsverteilung in den Gruppen. Das Patientenalter (MANCOVA; p < 0,021), nicht aber die VER hattesignifikanten Einfluß auf das psychopathologische Symptomprofil. Nach Ausblendung der Patientengruppe mit ubiquit{\"a}ren WMLblieb der Einfluß der WML-Verteilung auf die psychopathologische Symptomatiksignifikantc (p <0,05). Bifrontale WML waren mit Denkst{\"o}rung, rechts frontotemporale WML mit affektiven Symptomen assoziiert. Die Befunde sprechen f{\"u}r einen Einfluß der r{\"a}umlichen Verteilung unspezifischer Marklagerl{\"a}sionen auf die psychopathologische Symptomatik.},
  subject      = {Medizin},
  language  = {de}
}
@article{BenkertDietzHartmannetal.2012,
  author    = {Benkert, Thomas F. and Dietz, Lena and Hartmann, Elena M. and Leich, Ellen and Rosenwald, Andreas and Serfling, Edgar and Buttmann, Mathias and Berberich-Siebelt, Friederike},
  title     = {Natalizumab Exerts Direct Signaling Capacity and Supports a Pro-Inflammatory Phenotype in Some Patients with Multiple Sclerosis},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-77905},
  year      = {2012},
  abstract  = {Natalizumab is a recombinant monoclonal antibody raised against integrin alpha-4 (CD49d). It is approved for the treatment of patients with multiple sclerosis (MS), a chronic inflammatory autoimmune disease of the CNS. While having shown high therapeutic efficacy, treatment by natalizumab has been linked to progressive multifocal leukoencephalopathy (PML) as a serious adverse effect. Furthermore, drug cessation sometimes induces rebound disease activity of unknown etiology. Here we investigated whether binding of this adhesion-blocking antibody to T lymphocytes could modulate their phenotype by direct induction of intracellular signaling events. Primary CD4+ T lymphocytes either from healthy donors and treated with natalizumab in vitro or from MS patients receiving their very first dose of natalizumab were analyzed. Natalizumab induced a mild upregulation of IL-2, IFN-c and IL-17 expression in activated primary human CD4+ T cells propagated ex vivo from healthy donors, consistent with a pro-inflammatory costimulatory effect on lymphokine expression. Along with this, natalizumab binding triggered rapid MAPK/ERK phosphorylation. Furthermore, it decreased CD49d surface expression on effector cells within a few hours. Sustained CD49d downregulation could be attributed to integrin internalization and degradation. Importantly, also CD4+ T cells from some MS patients receiving their very first dose of natalizumab produced more IL-2, IFN-c and IL-17 already 24 h after infusion. Together these data indicate that in addition to its adhesion-blocking mode of action natalizumab possesses mild direct signaling capacities, which can support a pro-inflammatory phenotype of peripheral blood T lymphocytes. This might explain why a rebound of disease activity or IRIS is observed in some MS patients after natalizumab cessation.},
  subject      = {Medizin},
  language  = {en}
}
@phdthesis{Betz2005,
  author    = {Betz, Christian},
  title     = {Scalable authoring of diagnostic case based training systems},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-17885},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2005},
  abstract  = {Diagnostic Case Based Training Systems (D-CBT) provide learners with a means to learn and exercise knowledge in a realistic context. In medical education, D-CBT Systems present virtual patients to the learners who are asked to examine, diagnose and state therapies for these patients. Due a number of conflicting and changing requirements, e.g. time for learning, authoring effort, several systems were developed so far. These systems range from simple, easy-to-use presentation systems to highly complex knowledge based systems supporting explorative learning. This thesis presents an approach and tools to create D-CBT systems from existing sources (documents, e.g. dismissal records) using existing tools (word processors): Authors annotate and extend the documents to model the knowledge. A scalable knowledge representation is able to capture the content on multiple levels, from simple to highly structured knowledge. Thus, authoring of D-CBT systems requires less prerequisites and pre-knowledge and is faster than approaches using specialized authoring environments. Also, authors can iteratively add and structure more knowledge to adapt training cases to their learners needs. The theses also discusses the application of the same approach to other domains, especially to knowledge acquisition for the Semantic Web.},
  subject      = {Computerunterst{\"u}tztes Lernen},
  language  = {en}
}
@article{BeyrichLoefflerKobsaretal.2011,
  author    = {Beyrich, Claudia and L{\"o}ffler, J{\"u}rgen and Kobsar, Anna and Speer, Christian P. and Kneitz, Susanne and Eigenthaler, Martin},
  title     = {Infection of Human Coronary Artery Endothelial Cells by Group B Streptococcus Contributes to Dysregulation of Apoptosis, Hemostasis, and Innate Immune Responses [Research Article]},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68834},
  year      = {2011},
  abstract  = {Early onset sepsis due to group B streptococcus leads to neonatal morbidity, increased mortality, and long-term neurological deficencies. Interaction between septicemic GBS and confluent monolayers of human coronary artery endothelial cells (HCAECs) was analyzed by genome wide expression profiling. In total, 124 genes were differentially expressed (89 upregulated, 35 downregulated) based on a more than 3-fold difference to control HCAEC. Regulated genes are involved in apoptosis, hemostasis, oxidative stress response, infection, and inflammation. Regulation of selected genes and proteins identified in the gene array analysis was confirmed by Real-time RT-PCR assay (granulocy te chemotactic protein 2), ELISA (urokinase, cyclooxygenase 2, granulocyte chemotactic protein 1), and western blotting (Heme oxygenase1, BCL2 interacting protein) at various time points between 4 and 24 hours. These results indicate that GBS infection might influence signalling pathways leading to impaired function of the innate immune system and hemorrhagic and inflammatory complications during GBS sepsis.},
  subject      = {Medizin},
  language  = {en}
}
@article{BuschTschernitzThurneretal.2013,
  author    = {Busch, Albert and Tschernitz, Sebastian and Thurner, Anette and Kellersmann, Richard and Lorenz, Udo},
  title     = {Fatal Paraneoplastic Embolisms in Both Circulations in a Patient with Poorly Differentiated Neuroendocrine Tumour},
  series = {Case Reports in Vascular Medicine},
  journal   = {Case Reports in Vascular Medicine},
  doi       = {10.1155/2013/739427},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97335},
  year      = {2013},
  abstract  = {Arterial embolism with lower limb ischemia is a rare manifestation of paraneoplastic hypercoagulability in cancer patients. We report a unique case of fatal thromboembolism involving both circulations associated with a poorly differentiated neuroendocrine tumor of the lung with rapid progress despite high doses of unfractioned heparin and review the current literature on anticoagulative regimen in tumour patients.},
  language  = {en}
}
@incollection{CantoreggiGuptaLutz1993,
  author    = {Cantoreggi, S. and Gupta, R. C. and Lutz, Werner K.},
  title     = {An improved 32P-postlabelling assay for detection and quantitation of styrene 7,8-oxide-DNA adducts},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86305},
  publisher      = {Universit{\"a}t W{\"u}rzburg},
  year      = {1993},
  abstract  = {Using DNA modified with [7-3H]styrene 7,8-oxide (SO) in vitro we have standardized the 32P-postlabelling assay for detecting SO-DNA adducts. Nuclease P 1-enriched adducts were 32P-labelled and purified by high-salt ( 4.0 M ammonium formate, pH 6.1} C1s reverse-phase TLC. After elution from the layer with 2-butoxyethanol:H20 (4:6), adducts were separated by two-dimensional PEI cellulose TLC in non-urea solvents (2.0 M ammonium formate, pH 3.5, and 2.7 M sodium phosphate, pH 5.6). One major, three minor and several trace adducts were detected. The efficiency of the kinase reaction depended on the ATP concentration. Use of standard labelling conditions (['Y· 32P]ATP, <3000 Ci/mmol; <2 Mikromol) resulted in poor ( 4-7\%) adduct recovery. An ATP concentration of 40 Mikromol, however, increased the labeJling efficiency by a factor of 5-8 (35-55\% based on 3H-SO labelied DNA). The results indicate that the new separation technique is suitable for the relatively polar SO-DNA adducts and that high labelling efficiency can be achieved.},
  subject      = {Medizin},
  language  = {en}
}
@article{ChenPalmLeschetal.2011,
  author    = {Chen, Y. and Palm, F. and Lesch, K. P. and Gerlach, M. and Moessner, R. and Sommer, C.},
  title     = {5-hydroxyindolacetic acid (5-HIAA), a main metabolite of serotonin, is responsible for complete Freund's adjuvant-induced thermal hyperalgesia in mice},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68858},
  year      = {2011},
  abstract  = {Background: The role of serotonin (5-hydroxytrptamine, 5-HT) in the modulation of pain has been widely studied. Previous work led to the hypothesis that 5-hydroxyindolacetic acid (5-HIAA), a main metabolite of serotonin, might by itself influence pain thresholds. Results: In the present study, we investigated the role of 5-HIAA in inflammatory pain induced by intraplantar injection of complete Freund's adjuvant (CFA) into the hind paw of mice. Wild-type mice were compared to mice deficient of the 5-HT transporter (5-HTT-/- mice) using behavioral tests for hyperalgesia and high-performance liquid chromatography (HPLC) to determine tissue levels of 5-HIAA. Wild-type mice reproducibly developed thermal hyperalgesia and paw edema for 5 days after CFA injection. 5-HTT-/- mice treated with CFA had reduced thermal hyperalgesia on day 1 after CFA injection and normal responses to heat hereafter. The 5-HIAA levels in spinal cord and sciatic nerve as measured with HPLC were lower in 5-HTT-/- mice than in wild-type mice after CFA injection. Pretreatment of wild-type mice with intraperitoneal injection of para-chlorophenylalanine (p-CPA), a serotonin synthesis inhibitor, resulted in depletion of the 5-HIAA content in spinal cord and sciatic nerve and decrease in thermal hyperalgesia in CFA injected mice. The application of exogenous 5-HIAA resulted in potentiation of thermal hyperalgesia induced by CFA in 5-HTT-/- mice and in wild-type mice pretreated with p- CPA, but not in wild-type mice without p-CPA pretreatment. Further, methysergide, a broad-spectrum serotonin receptor antagonist, had no effect on 5-HIAA-induced potentiation of thermal hyperalgesia in CFA-treated wildtype mice. Conclusion: Taken together, the present results suggest that 5-HIAA plays an important role in modulating peripheral thermal hyperalgesia in CFA induced inflammation, probably via a non-serotonin receptor mechanism.},
  subject      = {Medizin},
  language  = {en}
}
@article{ChenBoettgerReifetal.2010,
  author    = {Chen, Yong and Boettger, Michael K. and Reif, Andreas and Schmitt, Angelika and Ueceyler, Nurcan and Sommer, Claudia},
  title     = {Nitric oxide synthase modulates CFA-induced thermal hyperalgesia through cytokine regulation in mice},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68349},
  year      = {2010},
  abstract  = {Background: Although it has been largely demonstrated that nitric oxide synthase (NOS), a key enzyme for nitric oxide (NO) production, modulates inflammatory pain, the molecular mechanisms underlying these effects remain to be clarified. Here we asked whether cytokines, which have well-described roles in inflammatory pain, are downstream targets of NO in inflammatory pain and which of the isoforms of NOS are involved in this process. Results: Intraperitoneal (i.p.) pretreatment with 7-nitroindazole sodium salt (7-NINA, a selective neuronal NOS inhibitor), aminoguanidine hydrochloride (AG, a selective inducible NOS inhibitor), L-N(G)-nitroarginine methyl ester (L-NAME, a non-selective NOS inhibitor), but not L-N(5)-(1-iminoethyl)-ornithine (L-NIO, a selective endothelial NOS inhibitor), significantly attenuated thermal hyperalgesia induced by intraplantar (i.pl.) injection of complete Freund's adjuvant (CFA). Real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed a significant increase of nNOS, iNOS, and eNOS gene expression, as well as tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1b), and interleukin-10 (IL-10) gene expression in plantar skin, following CFA. Pretreatment with the NOS inhibitors prevented the CFA-induced increase of the pro-inflammatory cytokines TNF and IL-1b. The increase of the antiinflammatory cytokine IL-10 was augmented in mice pretreated with 7-NINA or L-NAME, but reduced in mice receiving AG or L-NIO. NNOS-, iNOS- or eNOS-knockout (KO) mice had lower gene expression of TNF, IL-1b, and IL-10 following CFA, overall corroborating the inhibitor data. Conclusion: These findings lead us to propose that inhibition of NOS modulates inflammatory thermal hyperalgesia by regulating cytokine expression.},
  subject      = {Medizin},
  language  = {en}
}
@phdthesis{Ehrmann2007,
  author    = {Ehrmann, Christian},
  title     = {Outsourcing von medizinischen Daten - strafrechtlich betrachtet -},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-28917},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2007},
  abstract  = {Nach der vorliegenden Untersuchung zum Outsourcing medizinischer Daten aus strafrechtlicher Sicht kann folgendes Gesamtergebnis festgehalten werden. Beim Outsourcing medizinischer Daten sind regelm{\"a}ßig personenbezogene Informationen betroffen. Personenbezogene Information umfasst als Oberbegriff „Geheimnisse" i.S.v. \S 203 StGB sowie personenbezogene Daten im Sinne des Datenschutzrechts. Bei der Bestimmung des Personenbezuges ist es trotz der grunds{\"a}tzlichen Parallelgeltung von Datenschutzrecht und \S 203 StGB zul{\"a}ssig, auf Grunds{\"a}tze aus dem Datenschutzrecht zur{\"u}ckzugreifen. F{\"u}r den Outsourcer medizinischer Daten droht eine Strafbarkeit nach \S 203 StGB, wenn private IT-Dienstleistungsunternehmen vom schweigepflichtigen Outsourcer zur Erledigung von Aufgaben herangezogen werden und in Kontakt mit den Geheimnissen geraten. Daneben kann sich eine Strafbarkeit im Wege der Teilnahme an einer nach \S 203 StGB strafbaren Geheimnisverletzung ergeben. Bei Sachverhalten mit Auslandsbezug kann es dabei zu einer Anwendung deutschen Strafrechts kommen, wenn die Teilnahmehandlung im Inland sich auf ein im Ausland erfolgendes Outsourcing bezieht oder die Teilnahmehandlung im Ausland sich auf ein im Inland erfolgendes Outsourcing bezieht. Bei \S 85a SGB X und \S 44 BDSG k{\"o}nnen sich ausl{\"a}ndische Outsourcingpartner auch als Mitt{\"a}ter strafbar machen, da es sich bei diesen Delikten nicht um Sonderdelikte handelt. Allerdings l{\"a}sst sich durch eine entsprechende Gestaltung des Outsourcingvorhabens im Einzelfall, unabh{\"a}ngig davon, ob ein Schweigepflichtiger nach \S 203 Abs. 1 oder Abs. 2 StGB betroffen ist, eine Strafbarkeit vermeiden. Ansatz ist dabei die Tatbestandsebene des \S 203 StGB, n{\"a}mlich das Merkmal „Geheimnis" sowie das Merkmal „Offenbaren". So kann einerseits durch eine wirksame Verschl{\"u}sselung ein „Geheimnis" i.S.v. \S 203 StGB entfallen. Andererseits besteht die M{\"o}glichkeit, Mitarbeiter des privaten externen Dienstleistungsunternehmens als Gehilfen in den Kreis der zum Wissen Berufenen zu integrieren. Hierzu muss der Dritte an die Funktion des Schweigepflichtigen so angebunden werden, dass aus objektiv-normativer Sicht von einer tatbestandlichen Verantwortungseinheit gesprochen werden kann. Auf der Ebene der Rechtswidrigkeit l{\"a}sst sich der Gefahr einer Strafbarkeit nach \S 203 StGB durch eine Einwilligung begegnen. Außerhalb des Rechtfertigungsgrundes der Einwilligung bestehen f{\"u}r das Outsourcing von medizinischen Daten regelm{\"a}ßig keine strafrechtlichen Erlaubniss{\"a}tze. Allenfalls in unvorhergesehenen Ausnahmesituationen ist eine Rechtfertigung nach \S 34 StGB denkbar. F{\"u}r den Regelfall des Outsourcings ist \S 34 StGB nicht als Rechtfertigungsgrund tauglich. Neben einer Strafbarkeit nach \S 203 StGB kommt beim Outsourcing medizinischer Daten eine Strafbarkeit nach \S 44 BDSG bzw. nach entsprechenden Vorschriften der Landesdatenschutzgesetze sowie eine Strafbarkeit nach \S 85a SGB X in Betracht. Die Gefahr einer Strafbarkeit kann ausgeschlossen werden, wenn das Outsourcing datenschutzrechtlich bzw. sozialrechtlich zul{\"a}ssig ist. Neben der M{\"o}glichkeit einer Einwilligung, die nur ausdr{\"u}cklich erfolgen kann, ist die Zul{\"a}ssigkeit eines Outsourcings medizinischer Daten {\"u}ber eine Ausgestaltung als Auftragsdatenverarbeitung erreichbar. Vorschriften zur Auftragsdatenverarbeitung existieren sowohl im Datenschutzrecht als auch im Sozialrecht. Diese Vorschriften erm{\"o}glichen, sofern nicht spezielle Vorschriften des sektorspezifischen Datenschutzrechts wie beispielsweise Art. 27 Bayerisches Krankenhausgesetz entgegenstehen, in bestimmten Grenzen ein Outsourcing medizinischer Daten unter Beteiligung privater IT-Dienstleistungsunternehmen. Die Normen der Auftragsdatenverarbeitung erm{\"o}glichen nicht eine selbst{\"a}ndige und eigenverantwortliche Aufgabenerf{\"u}llung durch den Outsourcingnehmer im Sinne einer Funktions{\"u}bertragung. Vielmehr muss der Outsourcer nach einer Gesamtbetrachtung das Gesamtgeschehen erkennbar beherrschen und steuern. Die Aufgabe darf nicht durch den Auftraggeber insgesamt aus den H{\"a}nden gegeben werden. Andere Vorschriften, die eine Funktions{\"u}bertragung beim Outsourcing medizinischer Daten erm{\"o}glichen w{\"u}rden, bestehen nicht. Die straflose M{\"o}glichkeit des Outsourcings medizinischer Daten h{\"a}ngt von der Gestaltung im Einzelfall ab. Dies kann unter dem Aspekt der Rechtssicherheit und Rechtsklarheit beklagt werden. W{\"u}nschenswert ist eine bundeseinheitliche Regelung, die das Outsourcing strafrechtlich regelt. Unter den verschiedenen gesetzgeberischen M{\"o}glichkeiten ist eine Neuregelung des \S 203 StGB zu favorisieren.},
  subject      = {Schweigepflicht},
  language  = {de}
}
@article{FassnachtSbieraDexneitetal.2011,
  author    = {Fassnacht, Martin and Sbiera, Silviu and Dexneit, Thomas and Reichardt, Sybille D. and Michel, Kai D. and van den Brandt, Jens and Schmull, Sebastian and Kraus, Luitgard and Beyer, Melanie and Mlynski, Robert and Wortmann, Sebastian and Allolio, Bruno and Reichardt, Holger M.},
  title     = {Influence of Short-Term Glucocorticoid Therapy on Regulatory T Cells In Vivo},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-74749},
  year      = {2011},
  abstract  = {Background: Pre- and early clinical studies on patients with autoimmune diseases suggested that induction of regulatory T(Treg) cells may contribute to the immunosuppressive effects of glucocorticoids(GCs). Objective: We readdressed the influence of GC therapy on Treg cells in immunocompetent human subjects and na{\i}¨ve mice. Methods: Mice were treated with increasing doses of intravenous dexamethasone followed by oral taper, and Treg cells in spleen and blood were analyzed by FACS. Sixteen patients with sudden hearing loss but without an inflammatory disease received high-dose intravenous prednisolone followed by stepwise dose reduction to low oral prednisolone. Peripheral blood Treg cells were analyzed prior and after a 14 day GC therapy based on different markers. Results: Repeated GC administration to mice for three days dose-dependently decreased the absolute numbers of Treg cells in blood (100 mg dexamethasone/kg body weight: 2.861.86104 cells/ml vs. 336116104 in control mice) and spleen (dexamethasone: 2.861.96105/spleen vs. 956226105/spleen in control mice), which slowly recovered after 14 days taper in spleen but not in blood. The relative frequency of FOXP3+ Treg cells amongst the CD4+ T cells also decreased in a dose dependent manner with the effect being more pronounced in blood than in spleen. The suppressive capacity of Treg cells was unaltered by GC treatment in vitro. In immunocompetent humans, GCs induced mild T cell lymphocytosis. However, it did not change the relative frequency of circulating Treg cells in a relevant manner, although there was some variation depending on the definition of the Treg cells (FOXP3+: 4.061.5\% vs 3.461.5\%*; AITR+: 0.660.4 vs 0.560.3\%, CD127low: 4.061.3 vs 5.063.0\%* and CTLA4+: 13.8611.5 vs 15.6612.5\%; * p,0.05). Conclusion: Short-term GC therapy does not induce the hitherto supposed increase in circulating Treg cell frequency, neither in immunocompetent humans nor in mice. Thus, it is questionable that the clinical efficacy of GCs is achieved by modulating Treg cell numbers.},
  subject      = {Medizin},
  language  = {en}
}
@article{FehrholzBersaniKrameretal.2012,
  author    = {Fehrholz, Markus and Bersani, Iliana and Kramer, Boris W. and Speer, Christian P. and Kunzmann, Steffen},
  title     = {Synergistic Effect of Caffeine and Glucocorticoids on Expression of Surfactant Protein B (SP-B) mRNA},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-77927},
  year      = {2012},
  abstract  = {Administration of glucocorticoids and caffeine is a common therapeutic intervention in the neonatal period, but possible interactions between these substances are still unclear. The present study investigated the effect of caffeine and different glucocorticoids on expression of surfactant protein (SP)-B, crucial for the physiological function of pulmonary surfactant. We measured expression levels of SP-B, various SP-B transcription factors including erythroblastic leukemia viral oncogene homolog 4 (ErbB4) and thyroid transcription factor-1 (TTF-1), as well as the glucocorticoid receptor (GR) after administering different doses of glucocorticoids, caffeine, cAMP, or the phosphodiesterase-4 inhibitor rolipram in the human airway epithelial cell line NCI-H441. Administration of dexamethasone (1 mM) or caffeine (5 mM) stimulated SP-B mRNA expression with a maximal of 38.8611.1-fold and 5.261.4-fold increase, respectively. Synergistic induction was achieved after coadministration of dexamethasone (1 mM) in combination with caffeine (10 mM) (206659.7-fold increase, p,0.0001) or cAMP (1 mM) (2136111-fold increase, p = 0.0108). SP-B mRNA was synergistically induced also by administration of caffeine with hydrocortisone (87.9639.0), prednisolone (154666.8), and betamethasone (12366.4). Rolipram also induced SP-B mRNA (64.9621.0-fold increase). We detected a higher expression of ErbB4 and GR mRNA (7.0- and 1.7-fold increase, respectively), whereas TTF-1, Jun B, c-Jun, SP1, SP3, and HNF-3a mRNA expression was predominantly unchanged. In accordance with mRNA data, mature SP-B was induced significantly by dexamethasone with caffeine (13.869.0-fold increase, p = 0.0134). We found a synergistic upregulation of SP-B mRNA expression induced by co-administration of various glucocorticoids and caffeine, achieved by accumulation of intracellular cAMP. This effect was mediated by a caffeinedependent phosphodiesterase inhibition and by upregulation of both ErbB4 and the GR. These results suggested that caffeine is able to induce the expression of SP-transcription factors and affects the signaling pathways of glucocorticoids, amplifying their effects. Co-administration of caffeine and corticosteroids may therefore be of benefit in surfactant homeostasis.},
  subject      = {Medizin},
  language  = {en}
}
@article{FeuersteinSiren1987,
  author    = {Feuerstein, G. and Sir{\´e}n, Anna-Leena},
  title     = {Cardiovascular effects of enkephalins},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-49048},
  year      = {1987},
  abstract  = {Enkephalins and their receptors are found in neurons and nerve terminals known to be involved in central cardiovascular control as well as the peripheral sympathetic and parasympathetic systems. Enkephalins and opioid receptors were also iden tified in the heart, kidneys, and blood vessels. The enkephalins interact with several specific receptors, of which p, 0, and K have been best characterized. Enkephalins administered to humans or animals produce cardiovascular effects which depend on the spedes, route of administration, anesthesia, and the selectivity for receptor subtype. While little information exists on the role of enkephalins in normal cardiovascular control, current data suggest that enkephalins might have a role in cardiovascular stress responses such os in shock and trauma.},
  subject      = {Medizin},
  language  = {en}
}
@article{FeuersteinSiren1986,
  author    = {Feuerstein, G. and Sir{\´e}n, Anna-Leena},
  title     = {Effect of naloxone and morphine on survival of conscious rats after hemorrhage},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-48669},
  year      = {1986},
  abstract  = {The endogenous opioid system has been reported to depress the cardiovascular system during shock states, since naloxone, a potent opiate antagonist, enhances recovery of hemodynamic variables in various shock states. However, the effect of naloxone on long-term survival of experimental animals exposed to hypovolemic hypotension is not clear. The present studies tested the capacity of various doses of naloxone to protect conscious rats from mortality following various bleeding paradigms. In addition, the effect of morphine on survival of rats exposed to hemorrhage was also examined. In the six different experimental protocols tested, naloxone treatments failed to improve short- or long-term survival; in fact, naloxone treatment reduced short-term survival in two of the experimental protocols. Morphine injection, however, enhanced the mortality of rats exposed to hemorrhage in a dose-dependent manner. It is concluded that while opiates administered exogenously decrease survival after acute bleeding, naloxone has no protective action in such states and, like morphine, it may decrease survival in some situations.},
  subject      = {Medizin},
  language  = {en}
}
@article{FeuersteinSirenGoldsteinetal.1989,
  author    = {Feuerstein, G. and Sir{\´e}n, Anna-Leena and Goldstein, DS and Johnson, AK and Zerbe, RL},
  title     = {The effect of morphine on the hemodynamic and neuroendocrine responses to hemorrhagic shock in conscious rats},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-49033},
  year      = {1989},
  abstract  = {We have previously reported that analgesic doses of morphine accelerate mortality of rats exposed to hemorrhage (Feuerstein and Siren: Circ Shock 19:293-300, 1986). To study the potential mechanisms involved in this phenomenon, rats were chronically implanted with catheters in the femoral vessels and morphine (1.5 or 5 mg/kg) was administered 30 min or 24 hr after bleeding (8.5 mll300 g over 5 min) while arterial blood pressure and heart rate were continuously monitored. Furthermore, the effect of morphine (5 mg/kg) on cardiac output (CO) response to hemorrhage was studied in rats chronically equipped with a mini thermistor for CO monitoring by a thermodilution technique. In addition, plasma catecholamines (HPLC), plasma renin activity (PRA, RIA), vasopressin (RIA), pH, and blood gases were also determined. Morphine administration 30 min after hemorrhage produced a pressor response and tachycardia which were in marked contrast to its depressor effect in intact rats. Morphine elevated PRA and epinephrine but not vasopressin, while blood pH and gases showed no consistent change as compared to salinetreated hemorrhaged rats. Morphine given after the bleeding resulted in enhanced cardiac depression in response to a second bleed of 2 m1l300 g. Our data suggest that activation of pressor mechanisms by morphine during hypovolemic hypotension might enhance vasoconstriction in essential organs, depress cardiac function, and further reduce effective tissue perfusion.},
  subject      = {Medizin},
  language  = {en}
}
@article{FeuersteinSiren1987,
  author    = {Feuerstein, Giora and Sir{\´e}n, Anna-Leena},
  title     = {The Opioid System in cardiac and vascular regulation of normal and hypertensive states},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-47418},
  year      = {1987},
  abstract  = {The endogenous opioid system includes three major families of peptides: dynorphins (derived from pre-proenkephalin B), endorphins (derived from pre-proopiomelanocortin), and enkephalins (derived from pre-proenkephalin A). Multiple species of opioid peptides are derived from these major precursors and many of them possess potent cardiovascular properties. Opioid peptides and opioid receptors, of which multiple forms have been defined, are present in the central nervous system and peripheral neural elements. In the central nervous system, opioid peptides and receptors are found in forebrain and hindbrain nuclei involved in baroregulation, sympathoadrenal activation, and several other vital autonomic functions. In the periphery, opioid peptides are found in autonomic ganglia, adrenal gland, heart, and other organs; multiple opioid receptors are also found in vascular tissue, heart, and kidneys. Although little is known to date on the regulatory mechanisms of the opioid system in normal cardiovascular states, it became clear that cardiovascular stress situations substantially modify the activity of the endogenous opioid system. The purpose of this review is to clarify the sites of interaction of the opioid system with all major components of the cardiovascular system and indicate the potential role of this system in the ontogenesis of cardiac malfunction, vascular diseases, and hypertension.},
  subject      = {Medizin},
  language  = {en}
}
@article{FreyHoubenBroecker2010,
  author    = {Frey, Li­dia M. and Houben, Roland and Br{\"o}cker, Eva-B.},
  title     = {Pigmentation, Melanocyte Colonization, and p53 Status in Basal Cell Carcinoma},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68283},
  year      = {2010},
  abstract  = {Basal cell carcinoma (BCC) is the most common neoplasm in the Caucasian population. Only a fraction of BCC exhibits pigmentation. Lack of melanocyte colonization has been suggested to be due to p53-inactivating mutations in the BCC cells interfering with the p53-proopiomelanocortin pathway and the production of alpha melanocyte-stimulating hormone in the tumor. To evaluate this, we determined tumor pigmentation as well as expression of melan-A and of p53 in 49 BCC tissues bymeans of immunohistochemistry. As expected, we observed a positive relation between tumor pigmentation and melan-A positive intratumoral melanocytes.Melanocyte colonization and, to a lesser extent, p53 overexpression showed intraindividual heterogeneity in larger tumors. p53 overexpression, which is indicative of p53 mutations, was not correlated to melanocyte colonization of BCC. Sequencing of exon 5-8 of the p53 gene in selected BCC cases revealed that colonization by melanocytes and BCC pigmentation is neither ablated by p53 mutations nor generally present in BCCs with wild-type p53.},
  subject      = {Medizin},
  language  = {en}
}
@article{FreyJansenDohtetal.2013,
  author    = {Frey, S{\"o}nke Percy and Jansen, Hendrik and Doht, Stefanie and Filgueira, Luis and Zellweger, Rene},
  title     = {Immunohistochemical and Molecular Characterization of the Human Periosteum},
  series = {The Scientific World Journal},
  journal   = {The Scientific World Journal},
  doi       = {10.1155/2013/341078},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96623},
  year      = {2013},
  abstract  = {Purpose. The aim of the present study was to characterize the cell of the human periosteum using immunohistological and molecular methods. Methods. Phenotypic properties and the distribution of the cells within the different layers were investigated with immunohistochemical staining techniques and RT-PCR, focussing on markers for stromal stem cells, osteoblasts, osteoclasts and immune cells. Results. Immunohistochemical results revealed that all stained cells were located in the cambium layer and that most cells were positive for vimentin. The majority of cells consisted of stromal stem cells and osteoblastic precursor cells. The density increased towards the deeper layers of the cambium. In addition, cells positive for markers of the osteoblast, chondrocyte, and osteoclast lineages were found. Interestingly, there were MHC class II-expressing immune cells suggesting the presence of dendritic cells. Using lineage-specific primer pairs RT-PCR confirmed the immunofluorescence microscopy results, supporting that human periosteum serves as a reservoir of stromal stem cells, as well as cells of the osteoblastic, and the chondroblastic lineage, osteoclasts, and dendritic cells. Conclusion. Our work elucidates the role of periosteum as a source of cells with a high regenerative capacity. Undifferentiated stromal stem cells as well as osteoblastic precursor cells are dominating in the cambium layer. A new outlook is given towards an immune response coming from the periosteum as MHC II positive immune cells were detected.},
  language  = {en}
}
@article{GattenloehnerJoerissenHuhnetal.2010,
  author    = {Gattenloehner, Stefan and Joerissen, H. and Huhn, M. and Vincent, A. and Beeson, D. and Tzartos, S. and Mamalaki, A. and Etschmann, B. and Muller-Hermelink, H. K. and Koscielniak, E. and Barth, S. and Marx, A.},
  title     = {A Human Recombinant Autoantibody-Based Immunotoxin Specific for the Fetal Acetylcholine Receptor Inhibits Rhabdomyosarcoma Growth In Vitro and in a Murine Transplantation Model [Research Article]},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68200},
  year      = {2010},
  abstract  = {Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumor in children and is highly resistant to all forms of treatment currently available once metastasis or relapse has commenced. As it has recently been determined that the acetylcholine receptor (AChR) γ-subunit, which defines the fetal AChR (fAChR) isoform, is almost exclusively expressed in RMS post partum, we recombinantly fused a single chain variable fragment (scFv) derived from a fully human anti-fAChR Fab-fragment to Pseudomonas exotoxin A to generate an anti-fAChR immunotoxin (scFv35-ETA).While scFv35-ETA had no damaging effect on fAChR-negative control cell lines, it killed human embryonic and alveolar RMS cell lines in vitro and delayed RMS development in a murine transplantation model. These results indicate that scFv35-ETA may be a valuable new therapeutic tool as well as a relevant step towards the development of a fully human immunotoxin directed against RMS. Moreover, as approximately 20\% of metastatic malignant melanomas (MMs) display rhabdoid features including the expression of fAChR, the immunotoxin we developed may also prove to be of significant use in the treatment of these more common and most often fatal neoplasms.},
  subject      = {Medizin},
  language  = {en}
}
@article{GeisWeishauptGruenewaldetal.2011,
  author    = {Geis, Christian and Weishaupt, Andreas and Gr{\"u}newald, Benedikt and Wultsch, Thomas and Reif, Andreas and Gerlach, Manfred and Dirkx, Ron and Solimena, Michele and Perani, Daniela and Heckmann, Manfred and Toyka, Klaus V. and Folli, Franco and Sommer, Claudia},
  title     = {Human Stiff-Person Syndrome IgG Induces Anxious Behavior in Rats},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-74757},
  year      = {2011},
  abstract  = {Background: Anxiety is a heterogeneous behavioral domain playing a role in a variety of neuropsychiatric diseases. While anxiety is the cardinal symptom in disorders such as panic disorder, co-morbid anxious behavior can occur in a variety of diseases. Stiff person syndrome (SPS) is a CNS disorder characterized by increased muscle tone and prominent agoraphobia and anxiety. Most patients have high-titer antibodies against glutamate decarboxylase (GAD) 65. The pathogenic role of these autoantibodies is unclear. Methodology/Principal Findings: We re-investigated a 53 year old woman with SPS and profound anxiety for GABA-A receptor binding in the amygdala with (11)C-flumazenil PET scan and studied the potential pathogenic role of purified IgG from her plasma filtrates containing high-titer antibodies against GAD 65. We passively transferred the IgG fraction intrathecally into rats and analyzed the effects using behavioral and in vivo electrophysiological methods. In cell culture, we measured the effect of patient IgG on GABA release from hippocampal neurons. Repetitive intrathecal application of purified patient IgG in rats resulted in an anxious phenotype resembling the core symptoms of the patient. Patient IgG selectively bound to rat amygdala, hippocampus, and frontal cortical areas. In cultured rat hippocampal neurons, patient IgG inhibited GABA release. In line with these experimental results, the GABA-A receptor binding potential was reduced in the patient's amygdala/hippocampus complex. No motor abnormalities were found in recipient rats. Conclusion/Significance: The observations in rats after passive transfer lead us to propose that anxiety-like behavior can be induced in rats by passive transfer of IgG from a SPS patient positive for anti-GAD 65 antibodies. Anxiety, in this case, thus may be an antibody-mediated phenomenon with consecutive disturbance of GABAergic signaling in the amygdala region.},
  subject      = {Medizin},
  language  = {en}
}
@article{GeissingerSadlerRothetal.2010,
  author    = {Geissinger, Eva and Sadler, Petra and Roth, Sabine and Grieb, Tina and Puppe, Bernhard and Mueller, Nora and Reimer, Peter and Vetter-Kauczok, Claudia S. and Wenzel, Joerg and Bonzheim, Irina and Ruediger, Thomas and Mueller-Hermelink, Hans Konrad and Rosenwald, Andreas},
  title     = {Disturbed expression of the T-cell receptor/CD3 complex and associated signaling molecules in CD30(+) T-cell lymphoproliferations},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68179},
  year      = {2010},
  abstract  = {Background CD30+ T-cell lymphoproliferations comprise a spectrum of clinically heterogeneous entities, including systemic anaplastic large cell lymphomas (ALK- and ALK+) and primary cutaneous CD30+ T-cell lymphoproliferative disorders. While all these entities are characterized by proliferation of highly atypical, anaplastic CD30+ T cells, the expression of T-cell specific antigens in the tumor cells is not consistently detectable. Design and Methods We evaluated biopsies from 19 patients with primary cutaneous CD30+ lymphoproliferative disorders, 38 with ALK- and 33 with ALK+ systemic anaplastic large cell lymphoma. The biopsies were examined for the expression of T-cell receptoraβ/CD3 complex (CD3γ, δ, ε, ζ), transcription factors regulating T-cell receptor expression (ATF1, ATF2, TCF-1, TCF-1a/LEF-1, Ets1), and molecules of T-cell receptor-associated signaling cascades (Lck, ZAP-70, LAT, bcl-10, Carma1, NFATc1, c-Jun, c-Fos, Syk) using immunohistochemistry. Results In comparison to the pattern in 20 peripheral T-cell lymphomas, not otherwise specified, we detected a highly disturbed expression of the T-cell receptor/CD3 complex, TCF-1, TCF- 1a/LEF-1, Lck, ZAP-70, LAT, NFATc1, c-Jun, c-Fos and Syk in most of the systemic anaplastic large cell lymphomas. In addition, primary cutaneous CD30+ lymphoproliferative disorders showed such a similar expression pattern to that of systemic anaplastic large cell lymphomas, that none of the markers we investigated can reliably distinguish between these CD30+ T-cell lymphoproliferations. Conclusions Severely altered expression of the T-cell receptor/CD3 complex, T-cell receptor-associated transcription factors and signal transduction molecules is a common characteristic of systemic and cutaneous CD30+ lymphoproliferations, although the clinical behavior of these entities is very different. Since peripheral T-cell lymphomas, not otherwise specified retain the full expression program required for functioning T-cell receptor signaling, the differential expression of a subset of these markers might be of diagnostic utility in distinguishing peripheral T-cell lymphomas, not otherwise specified from the entire group of CD30+ lymphoproliferations.},
  subject      = {Medizin},
  language  = {en}
}
@article{GrimmLazariotouKircheretal.2010,
  author    = {Grimm, Martin and Lazariotou, Maria and Kircher, Stefan and Stuermer, Luisa and Reiber, Christoph and Hoefelmayr, Andreas and Gattenloehner, Stefan and Otto, Christoph and Germer, Christoph T. and von Rahden, Burkhard H. A.},
  title     = {MMP-1 is a (pre-)invasive factor in Barrett-associated esophageal adenocarcinomas and is associated with positive lymph node status},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68293},
  year      = {2010},
  abstract  = {Background: Esophageal adenocarcinomas (EACs) arise due to gastroesophageal reflux, with Barrett's esophagus (BE) regarded as precancerous lesion. Matrix metalloproteinases (MMPs) might play a role during the multistep carcinogenetic process. Methods: Expression of MMP-1 and -13 was analyzed in esophageal cancer (n = 41 EAC with BE, n = 19 EAC without BE, and n = 10 esophageal squamous-cell carcinomas, ESCC), furthermore in BE without intraepithelial neoplasia (IN) (n = 18), and the cell line OE-33. MMP-1 was co-labelled with Ki-67 (proliferation), Cdx-2 (marker for intestinal metaplasia, BE) and analyzed on mRNA level. MMP-1 staining results were correlated with clinicopatholocical parameters. Results: On protein level, MMP-1 expression was found in 39 of 41 (95\%) EAC with BE, in 19 of 19 (100\%) EAC without BE, in 6 of 10 (60\%) ESCC, and in 10 of 18 (56\%) BE without IN. No expression of MMP-13 was found in these specimens. Quantification showed 48\% MMP-1 positive cells in EAC with BE, compared to 35\% in adjacent BE (p < 0.05), 44\% in EAC without BE, 32\% in ESCC, and 4\% in BE without IN. Immunofluorescence double staining experiments revealed increased MMP-1 expressing in proliferating cells (MMP-1+/Ki-67+) (r = 0.943 for BE and r = 0.811 for EAC). On mRNA-level, expression of MMP-1 was significantly higher in EAC compared to BE (p = 0.01) and confirmed immunohistochemical staining results. High MMP-1 levels were associated with lymph node metastases but not with poorer survival (p = 0.307). Conclusions: Our findings suggest that MMP-1 plays a role as preinvasive factor in BE-associated EAC. Expression of MMP-1 in proliferating BE and EAC cells suggest malignant proliferation following the clonal expansion model.},
  subject      = {Medizin},
  language  = {en}
}
@article{GuckenbergerAlexandrowFlentje2012,
  author    = {Guckenberger, Matthias and Alexandrow, Nikolaus and Flentje, Michael},
  title     = {Radiotherapy alone for stage I-III low grade follicular lymphoma: long-term outcome and comparison of extended field and total nodal irradiation},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75702},
  year      = {2012},
  abstract  = {Background: To analyze long-term results of radiotherapy alone for stage I-III low grade follicular lymphoma and to compare outcome after extended field irradiation (EFI) and total nodal irradiation (TNI). Methods and materials: Between 1982 and 2007, 107 patients were treated with radiotherapy alone for low grade follicular lymphoma at Ann Arbor stage I (n = 50), II (n = 36) and III (n = 21); 48 and 59 patients were treated with EFI and TNI, respectively. The median total dose in the first treatment series of the diaphragmatic side with larger lymphoma burden was 38 Gy (25 Gy - 50 Gy) and after an interval of median 30 days, a total dose of 28 Gy (12.6 Gy - 45 Gy) was given in the second treatment series completing TNI. Results: After a median follow-up of 14 years for living patients, 10-years and 15-years overall survival (OS) were 64\% and 50\%, respectively. Survival was not significantly different between stages I, II and III. TNI and EFI resulted in 15-years OS of 65\% and 34\% but patients treated with TNI were younger, had better performance status and higher stage of disease compared to patients treated with EFI. In multivariate analysis, only age at diagnosis (p<0.001, relative risk [RR] 1.06) and Karnofsky performance status (p = 0.04, RR = 0.96) were significantly correlated with OS. Freedom from progression (FFP) was 58\% and 56\% after 10-years and 15-years, respectively. Recurrences outside the irradiated volume were significantly reduced after TNI compared to EFI; however, increased rates of in-field recurrences and extra-nodal out-of-field recurrence counterbalanced this effect resulting in no significant difference in FFP between TNI and EFI. In univariate analysis, FFP was significantly improved in stage I compared to stage II but no differences were observed between stages I/II and stage III. In multivariate analysis no patient or treatment parameter was correlated with FFP. Acute toxicity was significantly increased after TNI compared to EFI with a trend to increased late toxicity as well. Conclusions: Radiotherapy alone for stage I and II follicular lymphoma resulted in long-term OS with high rates of disease control; no benefit of TNI over EFI was observed. For stage III follicular lymphoma, TNI achieved promising OS and FFP and should be considered as a potentially curative treatment option.},
  subject      = {Medizin},
  language  = {en}
}
@article{GuckenbergerHawkinsFlentjeetal.2012,
  author    = {Guckenberger, Matthias and Hawkins, Maria and Flentje, Michael and Sweeney, Reinhart A.},
  title     = {Fractionated radiosurgery for painful spinal metastases: DOSIS - a phase II trial},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75853},
  year      = {2012},
  abstract  = {Background One third of all cancer patients will develop bone metastases and the vertebral column is involved in approximately 70 \% of these patients. Conventional radiotherapy with of 1-10 fractions and total doses of 8-30 Gy is the current standard for painful vertebral metastases; however, the median pain response is short with 3-6 months and local tumor control is limited with these rather low irradiation doses. Recent advances in radiotherapy technology - intensity modulated radiotherapy for generation of highly conformal dose distributions and image-guidance for precise treatment delivery - have made dose-escalated radiosurgery of spinal metastases possible and early results of pain and local tumor control are promising. The current study will investigate efficacy and safety of radiosurgery for painful vertebral metastases and three characteristics will distinguish this study. 1) A prognostic score for overall survival will be used for selection of patients with longer life expectancy to allow for analysis of long-term efficacy and safety. 2) Fractionated radiosurgery will be performed with the number of treatment fractions adjusted to either good (10 fractions) or intermediate (5 fractions) life expectancy. Fractionation will allow inclusion of tumors immediately abutting the spinal cord due to higher biological effective doses at the tumor - spinal cord interface compared to single fraction treatment. 3) Dose intensification will be performed in the involved parts of the vertebrae only, while uninvolved parts are treated with conventional doses using the simultaneous integrated boost concept. Methods / Design It is the study hypothesis that hypo-fractionated image-guided radiosurgery significantly improves pain relief compared to historic data of conventionally fractionated radiotherapy. Primary endpoint is pain response 3 months after radiosurgery, which is defined as pain reduction of ≥2 points at the treated vertebral site on the 0 to 10 Visual Analogue Scale. 60 patients will be included into this two-centre phase II trial. Conclusions Results of this study will refine the methods of patient selection, target volume definition, treatment planning and delivery as well as quality assurance for radiosurgery. It is the intention of this study to form the basis for a future randomized controlled trial comparing conventional radiotherapy with fractionated radiosurgery for palliation of painful vertebral metastases. Trial registration ClinicalTrials.gov Identifier: NCT01594892},
  subject      = {Medizin},
  language  = {en}
}
@article{GuckenbergerMantelGersztenetal.2014,
  author    = {Guckenberger, Matthias and Mantel, Frederick and Gerszten, Peter C. and Flickinger, John C. and Sahgal, Arjun and L{\´e}tourneau, Daniel and Grills, Inga S. and Jawad, Maha and Fahim, Daniel K. and Shin, John H. and Winey, Brian and Sheehan, Jason and Kersh, Ron},
  title     = {Safety and efficacy of stereotactic body radiotherapy as primary treatment for vertebral metastases: a multi-institutional analysis},
  doi       = {10.1186/s13014-014-0226-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-110638},
  year      = {2014},
  abstract  = {Purpose To evaluate patient selection criteria, methodology, safety and clinical outcomes of stereotactic body radiotherapy (SBRT) for treatment of vertebral metastases. Materials and methods Eight centers from the United States (n = 5), Canada (n = 2) and Germany (n = 1) participated in the retrospective study and analyzed 301 patients with 387 vertebral metastases. No patient had been exposed to prior radiation at the treatment site. All patients were treated with linac-based SBRT using cone-beam CT image-guidance and online correction of set-up errors in six degrees of freedom. Results 387 spinal metastases were treated and the median follow-up was 11.8 months. The median number of consecutive vertebrae treated in a single volume was one (range, 1-6), and the median total dose was 24 Gy (range 8-60 Gy) in 3 fractions (range 1-20). The median EQD210 was 38 Gy (range 12-81 Gy). Median overall survival (OS) was 19.5 months and local tumor control (LC) at two years was 83.9\%. On multivariate analysis for OS, male sex (p < 0.001; HR = 0.44), performance status <90 (p < 0.001; HR = 0.46), presence of visceral metastases (p = 0.007; HR = 0.50), uncontrolled systemic disease (p = 0.007; HR = 0.45), >1 vertebra treated with SBRT (p = 0.04; HR = 0.62) were correlated with worse outcomes. For LC, an interval between primary diagnosis of cancer and SBRT of ≤30 months (p = 0.01; HR = 0.27) and histology of primary disease (NSCLC, renal cell cancer, melanoma, other) (p = 0.01; HR = 0.21) were correlated with worse LC. Vertebral compression fractures progressed and developed de novo in 4.1\% and 3.6\%, respectively. Other adverse events were rare and no radiation induced myelopathy reported. Conclusions This multi-institutional cohort study reports high rates of efficacy with spine SBRT. At this time the optimal fractionation within high dose practice is unknown.},
  language  = {en}
}
@article{GuckenbergerRoeschBaieretal.2012,
  author    = {Guckenberger, Matthias and Roesch, Johannes and Baier, Kurt and Sweeney, Reinhart A. and Flentje, Michael},
  title     = {Dosimetric consequences of translational and rotational errors in frame-less image-guided radiosurgery},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75669},
  year      = {2012},
  abstract  = {Background: To investigate geometric and dosimetric accuracy of frame-less image-guided radiosurgery (IG-RS) for brain metastases. Methods and materials: Single fraction IG-RS was practiced in 72 patients with 98 brain metastases. Patient positioning and immobilization used either double- (n = 71) or single-layer (n = 27) thermoplastic masks. Pre-treatment set-up errors (n = 98) were evaluated with cone-beam CT (CBCT) based image-guidance (IG) and were corrected in six degrees of freedom without an action level. CBCT imaging after treatment measured intra-fractional errors (n = 64). Pre- and posttreatment errors were simulated in the treatment planning system and target coverage and dose conformity were evaluated. Three scenarios of 0 mm, 1 mm and 2 mm GTV-to-PTV (gross tumor volume, planning target volume) safety margins (SM) were simulated. Results: Errors prior to IG were 3.9 mm± 1.7 mm (3D vector) and the maximum rotational error was 1.7° ± 0.8° on average. The post-treatment 3D error was 0.9 mm± 0.6 mm. No differences between double- and single-layer masks were observed. Intra-fractional errors were significantly correlated with the total treatment time with 0.7mm±0.5mm and 1.2mm±0.7mm for treatment times ≤23 minutes and >23 minutes (p<0.01), respectively. Simulation of RS without image-guidance reduced target coverage and conformity to 75\% ± 19\% and 60\% ± 25\% of planned values. Each 3D set-up error of 1 mm decreased target coverage and dose conformity by 6\% and 10\% on average, respectively, with a large inter-patient variability. Pre-treatment correction of translations only but not rotations did not affect target coverage and conformity. Post-treatment errors reduced target coverage by >5\% in 14\% of the patients. A 1 mm safety margin fully compensated intra-fractional patient motion. Conclusions: IG-RS with online correction of translational errors achieves high geometric and dosimetric accuracy. Intra-fractional errors decrease target coverage and conformity unless compensated with appropriate safety margins.},
  subject      = {Medizin},
  language  = {en}
}
@article{GunrebenGeisKleinschnitz2013,
  author    = {Gunreben, Ignaz and Geis, Christian and Kleinschnitz, Christoph},
  title     = {Acute tetraparesis secondary to bilateral precentral gyral cerebral ischemia: a case report},
  series = {Journal of Medical Case Reports},
  journal   = {Journal of Medical Case Reports},
  doi       = {10.1186/1752-1947-7-61},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96179},
  year      = {2013},
  abstract  = {Introduction Sudden tetraparesis represents a neurological emergency and is most often caused by traumatic spinal cord injury, spinal epidural bleeding or brainstem ischemia and less frequently by medial disc herniation or spinal ischemia. Case presentation Here we report the rare case of an 82-year-old Caucasian man who developed severe tetraparesis four days after radical cystoprostatectomy. An emergency diagnostic study for spinal cord affection was normal. Brain magnetic resonance imaging revealed acute bilateral ischemic strokes in the precentral gyri as the underlying cause. Conclusions This case report underlines the need to also consider unusual causes of tetraparesis in an emergency situation apart from spinal cord or brain stem injury in order not to leave severe symptomatology unclear and possibly miss therapeutic options.},
  language  = {en}
}
@article{GuederBrennerAngermannetal.2012,
  author    = {G{\"u}der, G{\"u}lmisal and Brenner, Susanne and Angermann, Christiane E. and Ertl, Georg and Held, Matthias and Sachs, Alfred P. and Lammers, Jan Willem and Zanen, Peter and Hoes, Arno W. and St{\"o}rk, Stefan and Rutten, Frans H.},
  title     = {"GOLD or lower limit of normal definition? a comparison with expert-based diagnosis of chronic obstructive pulmonary disease in a prospective cohort-study"},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75193},
  year      = {2012},
  abstract  = {Background: The Global initiative for chronic Obstructive Lung Disease (GOLD) defines COPD as a fixed postbronchodilator ratio of forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC) below 0.7. Agedependent cut-off values below the lower fifth percentile (LLN) of this ratio derived from the general population have been proposed as an alternative. We wanted to assess the diagnostic accuracy and prognostic capability of the GOLD and LLN definition when compared to an expert-based diagnosis. Methods: In a prospective cohort study, 405 patients aged ≥ 65 years with a general practitioner's diagnosis of COPD were recruited and followed up for 4.5 (median; quartiles 3.9; 5.1) years. Prevalence rates of COPD according to GOLD and three LLN definitions and diagnostic performance measurements were calculated. The reference standard was the diagnosis of COPD of an expert panel that used all available diagnostic information, including spirometry and bodyplethysmography. Results: Compared to the expert panel diagnosis, 'GOLD-COPD' misclassified 69 (28\%) patients, and the three LLNs misclassified 114 (46\%), 96 (39\%), and 98 (40\%) patients, respectively. The GOLD classification led to more false positives, the LLNs to more false negative diagnoses. The main predictors beyond the FEV1/FVC ratio for an expert diagnosis of COPD were the FEV1 \% predicted, and the residual volume/total lung capacity ratio (RV/TLC). Adding FEV1 and RV/TLC to GOLD or LLN improved the diagnostic accuracy, resulting in a significant reduction of up to 50\% of the number of misdiagnoses. The expert diagnosis of COPD better predicts exacerbations, hospitalizations and mortality than GOLD or LLN. Conclusions: GOLD criteria over-diagnose COPD, while LLN definitions under-diagnose COPD in elderly patients as compared to an expert panel diagnosis. Incorporating FEV1 and RV/TLC into the GOLD-COPD or LLN-based definition brings both definitions closer to expert panel diagnosis of COPD, and to daily clinical practice.},
  subject      = {Medizin},
  language  = {en}
}
@article{Heinsen1977,
  author    = {Heinsen, Helmut},
  title     = {Quantitative anatomical studies on the postnatal development of the cerebellum of the albino rat},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-59881},
  year      = {1977},
  abstract  = {The quantitative postnatal changes of the cerebella of 65 Wistar rats aged 2-120 days have been examined. The cerebellar volume increases in two phases: The first phase lasts from birth to the seventh postnatal week. The second phase begins ten weeks post parturn and lasts for a Ionger period than the first phase. The cerebellar surface increases continuously from birth to the end of the seventh week. The volume of the external granular layer is maximal when the organ grows rapidly. The external granular layer has nearly disappeared 24 days after birth; the volume of the interaal granular layer is maximal at this time. Later on, the volume and the width of the interaal granular layer decrease. Myelinization of the cerebellar fibers and growth of the molecular layer run parallel to this decrease. The second late, but protracted growth of the cerebellum, ten weeks after birth, is due to an increase of the molecular and medullary layer. These findings are in good accord with histological, histochemical, and ultrastructural observations of other authors.},
  subject      = {Medizin},
  language  = {en}
}
@article{Heinsen1979,
  author    = {Heinsen, Helmut},
  title     = {Lipofuscin in the cerebellar cortex of albino rats: an electron microscopic study},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-59891},
  year      = {1979},
  abstract  = {The ultrastructure of autofluorescent, PAS-positive lipofuscin in Purkinje, granule, Golgi epithelial, basket and stellate, microglial and perivascular cells in the cerebellar cortex of senescent rats is described. The membrane- bounded pigment is composed ofthree elements: 1) electron-lucent homogeneaus droplets, 2) a granular matrix and 3) intensely osmiophilic patches. The proportians ofthese three components vary between cell types and one can grossly differentiate a neuronal and a gliallipofuscin. The lipofuscin granules of stellate and perivscular cells are different from lipofuscin of other cerebellar neurons and glia. lt can be concluded from these morphological observations that each cerebellar cell type has its distinct lipofuscin.},
  subject      = {Medizin},
  language  = {en}
}
@article{Heinsen1981,
  author    = {Heinsen, Helmut},
  title     = {Regional differences in the distribution of lipofuscin in Purkinje cell perikarya : a quantitative Pigmentarchitectonic study of the Cerebellar Cortexof Senile Albino Rats},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-59904},
  year      = {1981},
  abstract  = {The distribution of lipofuscin in the perikarya of Purkin je cells of vermal and hemispheric lobules has been determined quantitatively in 7 rats, 30-38 months old, by the point-counting method. On the basis of morphologically and statistically significant differences a pigmentarchitectonics of the cerebellar cortex is established. The Purkinje cells of lobule VIa (Larsell 1952) are extremely lipofuscin-rich. The Purkinje cells of the hemispheres, lobules V, Vlb + c and VII contain considerable amounts of a finely granular lipofuscin, the Purkinje cells of lobules I-III and VIII- IXa a globular type of lipofuscin. The Purkinje cells of sublobule XI d c and X are lipofuscin-poor cells. Three types of lipofuscin ha ve been identified in the light microscope.},
  subject      = {Medizin},
  language  = {en}
}
@article{HeinsenHeinsen1983,
  author    = {Heinsen, Helmut and Heinsen, Y. L.},
  title     = {Quantitative studies on regional differences in Purkinje cell dendritic spines and parallel fiber synaptic density},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-59917},
  year      = {1983},
  abstract  = {No abstact available},
  subject      = {Medizin},
  language  = {en}
}
@article{HeinsenHeinsen1983,
  author    = {Heinsen, Helmut and Heinsen, Y. L.},
  title     = {Cerebellar capillaries: qualitative and quantitative observations in young and senile rats},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-59924},
  year      = {1983},
  abstract  = {Ultrastructural changes including reduced electron density, reduction in polysemes and cisternae of rough endoplasmic reticulum occur in the cytoplasrn of endothelial cells and pericytes in the cerebellar cortex of senile virgin female Han: WIST-rats in cornparison to 3-month old virgin rats. Processes of pericytes cover less of the capillary surface in the cerebellar cortex of senile rats; moreover, arithmetic and harmonic mean thickness of the endothelium and relative volume of mitochondria in endothelial cells and pericytes are reduced, w hereas the luminal diameter of the capillaries, harmonic and arithmetic mean thickness of pericytes and their processes and of the basal laminae between endothelial cells and astrocytes (abbreviated BAL 1), pericytes and astrocytes (BAL 2) and endothelial cells and pericytes (BAL 3) increase. The increase in harmonic mean thickness of the basal laminae is statistically significant (α<=0.05) and compensates for a decrease in thickness of capillary endothelium. Consequently, the total barrier mass and thickness of cerebellar cortical capillaries in senile animals is higher than in young individuals.},
  subject      = {Medizin},
  language  = {en}
}
@article{HeinsenHeinsenBeckmannetal.1989,
  author    = {Heinsen, Helmut and Heinsen, Y. L. and Beckmann, H. and Gallyas, F. and Haas, S. and Scharff, G.},
  title     = {Laminar neuropathology in Alzheimer's disease by a modified Gallyas impregnation},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-59933},
  year      = {1989},
  abstract  = {No abstract available},
  subject      = {Medizin},
  language  = {en}
}
@article{HeinsenHennEisenmengeretal.1994,
  author    = {Heinsen, Helmut and Henn, R. and Eisenmenger, W. and G{\"o}tz, M. and Bohl, J. and Bethke, B. and Lockermann, U. and P{\"u}schel, K.},
  title     = {Quantitative investigations on the human entorhinal area: left - right asymmetry and age-related changes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-59946},
  year      = {1994},
  abstract  = {The total nerve cell numbers in the right and in the left human entorhinal areas have been calculated by volume estimations with the Cavalieri principle and by cell density determinations with the optical disector. Thick gallocyanin-stained serial frozen sections through the parahippocampal gyrus of 22 human subjects (10 female, 12 male) ranging from 18 to 86 years were analysed. The laminar composition of gallocyanin (Nissl)-stained sections could easily be compared with Braak's (1972, 1980) pigmentoarchitectonic study, and Braak's nomenclature of the entorhinal laminas was adopted. Cellsparse laminae dissecantes can more clearly be distinguished in Nissl than in aldehydefuchsin preparations. These cell-poor dissecantes, lamina dissecans extema (dis-ext), lamina dissecans 1 (dis-1) and lamina dissecans 2 (dis-2), were excluded from nerve cell nurober determinations. An exact delineation of the entorhinal area is indispensable for any kind of quantitative investigation. We have defined the entorhinal area by the presence of pre-alpha ceil clusters and the deeper layers of lamina principalis externa (pre-beta and gamma) separated from lamina principalis interna (pri) by lamina dissecans 1 (dis-1). The human entorhinal area is quantitatively characterized by a left-sided (asymmetric) higher pre-alpha cell number and an age-related nerve cell loss in pre as well as pri layers. At variance with other CNS cortical and subcortical structures, the neuronal number of the entorhinal area appears to decrease continuously from the earliest stages analysed, although a secular trend has to be considered. The asymmetry in pre-alpha cell number is discussed in the context of higher human mental capabilities, especially language.},
  subject      = {Medizin},
  language  = {en}
}
@article{HeinsenStrikLutheretal.1994,
  author    = {Heinsen, Helmut and Strik, M. and Luther, K. and Ulmar, G. and Gangnus, D. and Jungkunz, G. and Eisenmenger, W. and G{\"o}tz, M. and Bauer, M.},
  title     = {Cortical and striatal neurone number in Huntington's disease},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-55217},
  year      = {1994},
  abstract  = {The total cortical and striatal neurone and glial numbers were estimated in five cases of Huntington's disease (three males, two females) and five ageand sex-matched control cases. Serial 500-l-lm-thick gallocyanin-stained frontal sections through the left hemisphere were analysed using Cavalieri's principle for volume and the optical disector for cell density estimations. The average cortical neurone number of five controls (mean age 53±13 years, range 36-72 years) was 5.97x 109±320x 106 , the average number of small striatal neurones was 82 X 106± 15.8 X 106• The left striatum (caudatum, putamen, and accumbens) contained a mean of 273 X 106±53 X 106 glial cells (oligodendrocytes, astrocytes and unc1assifiable glial profiles). The mean cortical neurone number in Huntington's disease patients (mean age 49±14 years, range 36-75 years) was diminished by about 33 \% to 3.99x109±218x106 nerve cells (P ::;:::: 0.012, MannWhitney V-test). The mean number of small striatal neurones decreased tremendously to 9.72 X 106 ± 3.64 X 106 (-88 \% ). The decrease in total glial cells was less pronounced (193 X 106±26 X 106) but the mean glial index, the numerical ratio of glial cells per neurone, increased from 3.35 to 22.59 in Huntington's disease. Qualitatively, neuronal loss was most pronounced in supragranular layers of primary sensory areas (Brodmann's areae 3,1,2; area 17, area 41). Layer HIc pyramidal cells were preferentially lost in association areas of the temporal, frontal, and parietal lobes, whereas spared layer IV granule cells formed a conspicuous band between layer IH and V in these fields. Methodological issues are discussed in context with previous investigations and similarities and differences of laminar and lobar nerve cellloss in Huntington's disease are compared with nerve cell degent-ration in other neuropsychiatric diseases.},
  subject      = {Medizin},
  language  = {en}
}
@incollection{Herbert1994,
  author    = {Herbert, M. K.},
  title     = {Analgetikaeinsatz beim geriatrischen Patienten},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-78001},
  publisher      = {Universit{\"a}t W{\"u}rzburg},
  year      = {1994},
  abstract  = {Nicht nur bei traumatologischen, sondern auch bei vielen internistischen und neurologischen Notf{\"a}llen ist der Schmerz das oder eines der Leitsymptome. Neben der Wiederherstellung und Sicherung der Vitalfunktionen ist die rasche und effiziente Schmerzlinderung eine der wichtigsten Aufgaben des Notarztes. Eine erfolgreiche analgetische Therapie verbessert zum einen die subjektive Befindlichkeit des Patienten und unterbricht zum anderen die durch starke Schmerzen initiierten und unterhaltenen sympathiko-adrenergen und metabolisch-endokrinen Streßreaktionen, mit all ihren nachteiligen Auswirkungen auf die H{\"a}modynamik und Respiration. Letzteres ist eine wichtige, positive Wirkung einer guten analgetischen Therapie, insbesondere beim kranken geriatrischen Patienten, der in den Kompensationsm{\"o}glichkeiten einzelner Organsysteme oft deutlich eingeschr{\"a}nkt ist. L{\"a}nger fortbestehende starke Schmerzen w{\"u}rden gerade bei diesen Patienten eine Einschr{\"a}nkung der H{\"a}modynamik und Respiration perpetuieren.},
  subject      = {Medizin},
  language  = {de}
}
@article{HerbertHolzer1994,
  author    = {Herbert, M. K. and Holzer, P.},
  title     = {Nitric oxide mediates the amplification by interleukin-1β of neurogenic vasodilatation in the rat skin},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-59969},
  year      = {1994},
  abstract  = {No abstract available.},
  subject      = {Medizin},
  language  = {en}
}
@article{HerbertSchmidt1992,
  author    = {Herbert, M. K. and Schmidt, R. F.},
  title     = {Activation of normal and inflamed fine articular afferent units by serotonin},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-59952},
  year      = {1992},
  abstract  = {In cats anesthetized with alpha-chloralose, extracellular recordings were made from fine afferent units belonging to the medial articular nerve (MAN) of the knee joint. The excitatory and sensitizing effects on articular afferents of serotonin (5-HT) applied intra-arterially close to the joint were examined. The joints were either normal or an experimental arthritis had been induced some hours before the recording session. Bolus injections of 1.35-135 p,g 5-HT excited about 43\% of group 111 (CV: 2.5-20 m/sec) and 73\% of group IV units (CV: < 2.5 mjsec) from normal joints. The latency was usually between 10 and 30 sec, and the duration and size of the responses were dose-dependent. Fast group 111 units (CV: > 16 mjsec) and group li units (CV: > 20 m/sec) were never excited by 5-HT. Repetitiveadministration led to pronounced tachyphylaxis of the 5-HT response. Inflammation induced an enhanced sensitivity of group III articular afferent units to close intra-arterial application of 5-HT. In particular the total duration of each response was considerably prolonged (4-10 min against 1-2 min under normal conditions). At the same time the tachyphylaxis seen under normal conditions was gteatly reduced. In contrast, group IV articular afferent units did not become sensitized to 5-HT in the course of inflammation. In normal joints 5-HT did not sensitize fineafferent units for movement-induced responses. However, after inflammation, a distinct sensitization to such movements by 5-HT application could be observed bothin group 111 and group IV fiber ranges. The sensitization had a short time course not exceeding 7 min. The tonic component of the movement-induced response was more enhanced than the phasic one. The bolus application of 5-HT led to temporary vasoconstriction of the knee joint vessels. This vasoconstriction was especially pronounced in inflamed joints and impeded the access of subsequently applied substances to the terminal regions of the afferent units under observation. lt is concluded that the present results support the notion that 5-HT may participate in the mediation of pain from inflamed tissue such as an arthritic joint by exciting and sensitizing fine afferent units. During inflammation group 111 units are particularly sensitive to 5-HT and, thus, may carry the bulk of the 5-HT-induced nociceptive messages.},
  subject      = {Medizin},
  language  = {en}
}
@article{HolzapfelRechlLehneretal.2011,
  author    = {Holzapfel, Boris Michael and Rechl, Hans and Lehner, Stefan and Pilge, Hakan and Gollwitzer, Hans and Steinhauser, Erwin},
  title     = {Alloplastic Reconstruction of the Extensor Mechanism after Resection of Tibial Sarcoma [Research Article]},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-69072},
  year      = {2011},
  abstract  = {Reconstruction of the extensor mechanism is essential for good extremity function after endoprosthetic knee replacement following tumor resection. Only a few biological methods have been able to reliably restore a functional extensor mechanism, but they are often associated with significant complication rates. Reattachment of the patellar tendon to the prosthesis using an alloplastic patellar ligament (Trevira cord) can be an appropriate alternative. In vivo and in vitro studies have already shown that complete fibrous ingrowth in polyethylene chords can be seen after a period of six months. However, until now, no biomechanical study has shown the efficacy of an alloplastic cord and its fixation device in providing sufficient stability and endurance in daily life-activity until newly formed scar tissue can take over this function. In a special test bench developed for this study, different loading regimes were applied to simulate loads during everyday life. Failure loads and failuremodes were evaluated. The properties of the cord were compared before and after physiological conditioning. It was shown that rubbing was the mode of failure under dynamic loading. Tensile forces up to 2558N did not result in material failure. Thus, using an artificial cord together with this fixation device, temporary sufficient stable fixation can be expected.},
  subject      = {Medizin},
  language  = {en}
}
@article{HomolaJbabdiBeckmannetal.2012,
  author    = {Homola, Gy{\"o}rgy A. and Jbabdi, Saad and Beckmann, Christian F. and Bartsch, Andreas J.},
  title     = {A Brain Network Processing the Age of Faces},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75513},
  year      = {2012},
  abstract  = {Age is one of the most salient aspects in faces and of fundamental cognitive and social relevance. Although face processing has been studied extensively, brain regions responsive to age have yet to be localized. Using evocative face morphs and fMRI, we segregate two areas extending beyond the previously established face-sensitive core network, centered on the inferior temporal sulci and angular gyri bilaterally, both of which process changes of facial age. By means of probabilistic tractography, we compare their patterns of functional activation and structural connectivity. The ventral portion of Wernicke's understudied perpendicular association fasciculus is shown to interconnect the two areas, and activation within these clusters is related to the probability of fiber connectivity between them. In addition, post-hoc age-rating competence is found to be associated with high response magnitudes in the left angular gyrus. Our results provide the first evidence that facial age has a distinct representation pattern in the posterior human brain. We propose that particular face-sensitive nodes interact with additional object-unselective quantification modules to obtain individual estimates of facial age. This brain network processing the age of faces differs from the cortical areas that have previously been linked to less developmental but instantly changeable face aspects. Our probabilistic method of associating activations with connectivity patterns reveals an exemplary link that can be used to further study, assess and quantify structure-function relationships.},
  subject      = {Medizin},
  language  = {en}
}
@article{JakubietzGruenertJakubietz2011,
  author    = {Jakubietz, Michael G. and Gruenert, Joerg G. and Jakubietz, Rafael G.},
  title     = {The use of beta-tricalcium phosphate bone graft substitute in dorsally plated, comminuted distal radius fractures},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68829},
  year      = {2011},
  abstract  = {Background: Intraarticular distal radius fractures can be treated with many methods. While internal fixation with angle stable implants has become increasingly popular, the use of bone graft substitutes has also been recommended to address comminution zones and thus increase stability. Whether a combination of both methods will improve clinical outcomes was the purpose of the study Methods: The study was thus conducted as a prospective randomized clinical trial. 39 patients with unilateral, intraarticular fractures of the distal radius were included and randomized to 2 groups, one being treated with internal fixation only, while the second group received an additional bone graft substitute. Results: There was no statistical significance between both groups in functional and radiological results. The occurrence of complications did also not show statistical significance. Conclusions: No advantage of additional granular bone graft substitutes could be seen in this study. Granular bone graft substitutes do not seem to provide extra stability if dorsal angle stable implants are used. Dorsal plates have considerable complication rates such as extensor tendon ruptures and development of CRPS.},
  subject      = {Medizin},
  language  = {en}
}
@article{KannenHintzscheZanetteetal.2012,
  author    = {Kannen, Vinicius and Hintzsche, Henning and Zanette, Dalila L. and Silva Jr., Wilson A. and Garcia, Sergio B. and Waaga-Gasser, Anna Maria and Stopper, Helga},
  title     = {Antiproliferative Effects of Fluoxetine on Colon Cancer Cells and in a Colonic Carcinogen Mouse Model},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75879},
  year      = {2012},
  abstract  = {The antidepressant fluoxetine has been under discussion because of its potential influence on cancer risk. It was found to inhibit the development of carcinogen-induced preneoplastic lesions in colon tissue, but the mechanisms of action are not well understood. Therefore, we investigated anti-proliferative effects, and used HT29 colon tumor cells in vitro, as well as C57BL/6 mice exposed to intra-rectal treatment with the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) as models. Fluoxetine increased the percentage of HT29 cells in the G0/G1 phase of cell-cycle, and the expression of p27 protein. This was not related to an induction of apoptosis, reactive oxygen species or DNA damage. In vivo, fluoxetine reduced the development of MNNG-induced dysplasia and vascularization-related dysplasia in colon tissue, which was analyzed by histopathological techniques. An anti-proliferative potential of fluoxetine was observed in epithelial and stromal areas. It was accompanied by a reduction of VEGF expression and of the number of cells with angiogenic potential, such as CD133, CD34, and CD31-positive cell clusters. Taken together, our findings suggest that fluoxetine treatment targets steps of early colon carcinogenesis. This confirms its protective potential, explaining at least partially the lower colon cancer risk under antidepressant therapy.},
  subject      = {Medizin},
  language  = {en}
}
@article{KleinertRollBaumgaertneretal.2012,
  author    = {Kleinert, Stefan and Roll, Petra and Baumgaertner, Christian and Himsel, Andrea and Burkhardt, Harald and Mueller, Adelheid and Fleck, Martin and Feuchtenberger, Martin and Janett, Manfred and Tony, Hans-Peter},
  title     = {Renal Perfusion in Scleroderma Patients Assessed by Microbubble-Based Contrast-Enhanced Ultrasound},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75207},
  year      = {2012},
  abstract  = {Abstract: Objectives: Renal damage is common in scleroderma. It can occur acutely or chronically. Renal reserve might already be impaired before it can be detected by laboratory findings. Microbubble-based contrast-enhanced ultrasound has been demonstrated to improve blood perfusion imaging in organs. Therefore, we conducted a study to assess renal perfusion in scleroderma patients utilizing this novel technique. Materials and Methodology: Microbubble-based contrast agent was infused and destroyed by using high mechanical index by Siemens Sequoia (curved array, 4.5 MHz). Replenishment was recorded for 8 seconds. Regions of interests (ROI) were analyzed in renal parenchyma, interlobular artery and renal pyramid with quantitative contrast software (CUSQ 1.4, Siemens Acuson, Mountain View, California). Time to maximal Enhancement (TmE), maximal enhancement (mE) and maximal enhancement relative to maximal enhancement of the interlobular artery (mE\%A) were calculated for different ROIs. Results: There was a linear correlation between the time to maximal enhancement in the parenchyma and the glomerular filtration rate. However, the other parameters did not reveal significant differences between scleroderma patients and healthy controls. Conclusion: Renal perfusion of scleroderma patients including the glomerular filtration rate can be assessed using microbubble-based contrast media.},
  subject      = {Medizin},
  language  = {en}
}
@article{KleinschnitzMeuthMagnusetal.2012,
  author    = {Kleinschnitz, Christph and Meuth, Sven G. and Magnus, Tim and Korn, Thomas and Linker, Ralf A.},
  title     = {Report on the 3'rd scientific meeting of the "Verein zur F{\"o}rderung des Wissenschaftlichen Nachwuchses in der Neurologie" (NEUROWIND e.V.) held in Motzen, Germany, Nov. 4'th - Nov. 6'th, 2011},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75388},
  year      = {2012},
  abstract  = {From November 4th- 6th 2011, the 3rd NEUROWIND e.V. meeting was held in Motzen, Brandenburg, Germany. Like in the previous years, the meeting provided an excellent platform for scientific exchange and the presentation of innovative projects for young colleagues in the fields of neurovascular research, neuroinflammation and neurodegeneration. As kick-off to the scientific sessions, Reinhard Hohlfeld, Head of the Institute for Clinical Neuroimmunology in Munich, gave an illustrious overview on the many fascinations of neuroimmunologic research. A particular highlight on the second day of the meeting was the award of the 1'st NEUROWIND e.V. prize for young academics in the field of experimental neurology. This award is posted for young colleagues under the age of 35 with a significant achievement in the field of neurovascular research, neuroinflammation or neurodegeneration and comprises an amount of 20.000 Euro, founded by Merck Serono GmbH, Darmstadt. Germany. The first prize was awarded to Ivana Nikic from Martin Kerschensteiner's group in Munich for her brilliant work on a reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis, published in Nature Medicine in 2011. This first prize award ceremony was a great incentive for the next call for proposals now upcoming in 2012.},
  subject      = {Medizin},
  language  = {en}
}
@article{KlementKaemmerer2011,
  author    = {Klement, Rainer and K{\"a}mmerer, Ulrike},
  title     = {Is there a role for carbohydrate restriction in the treatment and prevention of cancer?},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-69178},
  year      = {2011},
  abstract  = {Over the last years, evidence has accumulated suggesting that by systematically reducing the amount of dietary carbohydrates (CHOs) one could suppress, or at least delay, the emergence of cancer, and that proliferation of already existing tumor cells could be slowed down. This hypothesis is supported by the association between modern chronic diseases like the metabolic syndrome and the risk of developing or dying from cancer. CHOs or glucose, to which more complex carbohydrates are ultimately digested, can have direct and indirect effects on tumor cell proliferation: first, contrary to normal cells, most malignant cells depend on steady glucose availability in the blood for their energy and biomass generating demands and are not able to metabolize significant amounts of fatty acids or ketone bodies due to mitochondrial dysfunction. Second, high insulin and insulin-like growth factor (IGF)-1 levels resulting from chronic ingestion of CHO-rich Western diet meals, can directly promote tumor cell proliferation via the insulin/IGF1 signaling pathway. Third, ketone bodies that are elevated when insulin and blood glucose levels are low, have been found to negatively affect proliferation of different malignant cells in vitro or not to be usable by tumor cells for metabolic demands, and a multitude of mouse models have shown antitumorigenic properties of very low CHO ketogenic diets. In addition, many cancer patients exhibit an altered glucose metabolism characterized by insulin resistance and may profit from an increased protein and fat intake. In this review, we address the possible beneficial effects of low CHO diets on cancer prevention and treatment. Emphasis will be placed on the role of insulin and IGF1 signaling in tumorigenesis as well as altered dietary needs of cancer patients.},
  subject      = {Medizin},
  language  = {en}
}
@article{KlingelhoefferKaemmererKoospaletal.2012,
  author    = {Klingelhoeffer, Chr{\´i}stoph and K{\"a}mmerer, Ulrike and Koospal, Monika and M{\"u}hling, Bettina and Schneider, Manuela and Kapp, Michaela and K{\"u}bler, Alexander, and Germer, Christoph-Thomas and Otto, Christoph},
  title     = {Natural resistance to ascorbic acid induced oxidative stress is mainly mediated by catalase activity in human cancer cells and catalase-silencing sensitizes to oxidative stress},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75142},
  year      = {2012},
  abstract  = {Background: Ascorbic acid demonstrates a cytotoxic effect by generating hydrogen peroxide, a reactive oxygen species (ROS) involved in oxidative cell stress. A panel of eleven human cancer cell lines, glioblastoma and carcinoma, were exposed to serial dilutions of ascorbic acid (5-100 mmol/L). The purpose of this study was to analyse the impact of catalase, an important hydrogen peroxide-detoxifying enzyme, on the resistance of cancer cells to ascorbic acid mediated oxidative stress. Methods: Effective concentration (EC50) values, which indicate the concentration of ascorbic acid that reduced the number of viable cells by 50\%, were detected with the crystal violet assay. The level of intracellular catalase protein and enzyme activity was determined. Expression of catalase was silenced by catalase-specific short hairpin RNA (sh-RNA) in BT-20 breast carcinoma cells. Oxidative cell stress induced apoptosis was measured by a caspase luminescent assay. Results: The tested human cancer cell lines demonstrated obvious differences in their resistance to ascorbic acid mediated oxidative cell stress. Forty-five percent of the cell lines had an EC50>20 mmol/L and fifty-five percent had an EC50<20 mmol/L. With an EC50 of 2.6-5.5 mmol/L, glioblastoma cells were the most susceptible cancer cell lines analysed in this study. A correlation between catalase activity and the susceptibility to ascorbic acid was observed. To study the possible protective role of catalase on the resistance of cancer cells to oxidative cell stress, the expression of catalase in the breast carcinoma cell line BT-20, which cells were highly resistant to the exposure to ascorbic acid (EC50: 94,9 mmol/L), was silenced with specific sh-RNA. The effect was that catalase-silenced BT-20 cells (BT-20 KD-CAT) became more susceptible to high concentrations of ascorbic acid (50 and 100 mmol/L). Conclusions: Fifty-five percent of the human cancer cell lines tested were unable to protect themselves against oxidative stress mediated by ascorbic acid induced hydrogen peroxide production. The antioxidative enzyme catalase is important to protect cancer cells against cytotoxic hydrogen peroxide. Silenced catalase expression increased the susceptibility of the formerly resistant cancer cell line BT-20 to oxidative stress.},
  subject      = {Medizin},
  language  = {en}
}
@article{KniesSchusterAmezianeetal.2012,
  author    = {Knies, Kerstin and Schuster, Beatrice and Ameziane, Najim and Rooimans, Martin and Bettecken, Thomas and de Winter, Johan and Schindler, Detlev},
  title     = {Genotyping of Fanconi Anemia Patients by Whole Exome Sequencing: Advantages and Challenges},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-77985},
  year      = {2012},
  abstract  = {Fanconi anemia (FA) is a rare genomic instability syndrome. Disease-causing are biallelic mutations in any one of at least 15 genes encoding members of the FA/BRCA pathway of DNA-interstrand crosslink repair. Patients are diagnosed based upon phenotypical manifestationsand the diagnosis of FA is confirmed by the hypersensitivity of cells to DNA interstrand crosslinking agents. Customary molecular diagnostics has become increasingly cumbersome, time-consuming and expensive the more FA genes have been identified. We performed Whole Exome Sequencing (WES) in four FA patients in order to investigate the potential of this method for FA genotyping. In search of an optimal WES methodology we explored different enrichment and sequencing techniques. In each case we were able to identify the pathogenic mutations so that WES provided both, complementation group assignment and mutation detection in a single approach. The mutations included homozygous and heterozygous single base pair substitutions and a two-base-pair duplication in FANCJ, -D1, or - D2. Different WES strategies had no critical influence on the individual outcome. However, database errors and in particular pseudogenes impose obstacles that may prevent correct data perception and interpretation, and thus cause pitfalls. With these difficulties in mind, our results show that WES is a valuable tool for the molecular diagnosis of FA and a sufficiently safe technique, capable of engaging increasingly in competition with classical genetic approaches.},
  subject      = {Medizin},
  language  = {en}
}
@article{KrannichThereseBroscheitetal.2012,
  author    = {Krannich, Jens-Holger and Therese, Tobias and Broscheit, Jens and Leyh, Rainer and M{\"u}llges, Wolfgang},
  title     = {Diabetes severely affects attentional performance after coronary artery bypass grafting},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75320},
  year      = {2012},
  abstract  = {Background: Diabetes is a risk factor for (micro) vascular damage of the brain, too. Therefore cognitive performance after coronary artery bypass grafting may be hypothesized worse in diabetics. To avoid observational errors a reliable tool for testing attentional performance was used. We evaluated whether diabetes mellitus disposes to distinct cognitive dysfunction after coronary artery bypass grafting (CABG). Methods: Three aspects in attentional performance were prospectively tested with three different tests (alertness: composed of un-cued and cued reaction, divided attention, and selective attention) by a computerized tool one day before and seven days after CABG in a highly selected cohort of 30 males, 10 of whom had diabetes. Statistical comparisons were done with analysis of variance for repeated measurements and Fisher´s LSD. Results: Prior to CABG there was no statistically meaningful difference between diabetics and non-diabetics. Postoperatively, diabetic patients performed significantly worse than non-diabetics in tests for un-cued (p=0.01) and cued alertness (p=0.03). Test performance in divided attention was worse after CABG but independent of diabetes status. Selective attention was neither affected by diabetes status nor by CABG itself. Conclusions: Diabetes may have an impact on cognitive performance after CABG. More severe deficits in alertness may point to underlying microvascular disease.},
  subject      = {Medizin},
  language  = {en}
}