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Billetoft, Birgitte ; Winter-Huneck, Brünhild ; Schnitter, Peer ; Frank, Dieter ; Bäse, Wolfgang ; Bartels, Roland ; Burger, Frank ; Dorn, Manfred ; Dornbusch, Gunthard ; Gohr, Friedemann ; Grosser, Clemens ; Gruschwitz, Wolfgang ; Haferkorn, Jörg ; Hanelt, Dorothea ; Hanelt, Peter ; Hohmann, Matthias ; Jäger, Urs G. ; Jage, Horst ; Jährling, Martina ; Jentzsch, Matthias ; Kammerad, Bernd ; Karisch, Timm ; Kleinsteuber, Wolfgang ; Körnig, Gerhard ; Komposch, Christian ; Lübke-Al Hussein, Marita ; Malchau, Werner ; Meyer, Frank ; Müller, Joachim ; Neumann, Volker ; Ohlendorf, Bernd ; Peterson, Jens ; Röhricht, Wieland ; Ruhnke, Haike ; Sacher, Peter ; Schmidt, Peter ; Schneider, Karla ; Scholz, Peter ; Scholze, Paul ; Schütze, Peter ; Schönborn, Christoph ; Spitzenberg, Dietmar ; Stark, Andreas ; Steglich, Rosmarie ; Stolle, Eckart ; Tappenbeck, Lutz ; Täuscher, Lothar ; Trost, Martin ; Wallaschek, Michael ; Wendt, Wolfgang ; Witsack, Werner ; Wüstemann, Otfried
Die vegetationskundliche und strukturelle Zuordnung der Lebensraumtypen erfolgt nach der vorrangig von Braun-Blanquet entwickelten Vegetationsklassifizierung, einer hierarchischen Gliederung der Vegetationstypen (Syntaxonomie), die die Ebenen der Assoziation, des Verbandes, der Ordnung und der Klasse umfasst. Hierbei ist die Assoziation die grundlegende Einheit, in der die Pflanzengesellschaften zusammengefasst werden, die sich durch gleiche charakteristische Arten(gruppen)kombinationen auszeichnen. Der Verband vereinigt ähnliche Assoziationen. Das sind bereits umfassendere, jedoch standörtlich noch recht einheitliche Vegetationseinheiten. In Ordnungen werden ähnliche Verbände zusammengefasst. Die Klasse vereinigt ähnliche Ordnungen.
Wöckel, Achim ; Festl, Jasmin ; Stüber, Tanja ; Brust, Katharina ; Stangl, Stephanie ; Heuschmann, Peter Ulrich ; Albert, Ute Susann ; Budach, Wilfried ; Follmann, Markus ; Janni, Wolfgang ; Kopp, Ina ; Kreienberg, Rolf ; Kühn, Thorsten ; Langer, Thomas ; Nothacker, Monika ; Scharl, Anton ; Schreer, Ingrid ; Link, Hartmut ; Engel, Jutta ; Fehm, Tanja ; Weis, Joachim ; Welt, Anja ; Steckelberg, Anke ; Feyer, Petra ; König, Klaus ; Hahne, Andrea ; Kreipe, Hans H. ; Knoefel, Wolfram Trudo ; Denkinger, Michael ; Brucker, Sara ; Lüftner, Diana ; Kubisch, Christian ; Gerlach, Christina ; Lebeau, Annette ; Siedentopf, Friederike ; Petersen, Cordula ; Bartsch, Hans Helge ; Schulz-Wendtland, Rüdiger ; Hahn, Markus ; Hanf, Volker ; Müller-Schimpfle, Markus ; Henscher, Ulla ; Roncarati, Renza ; Katalinic, Alexander ; Heitmann, Christoph ; Honegger, Christoph ; Paradies, Kerstin ; Bjelic-Radisic, Vesna ; Degenhardt, Friedrich ; Wenz, Frederik ; Rick, Oliver ; Hölzel, Dieter ; Zaiss, Matthias ; Kemper, Gudrun ; Budach, Volker ; Denkert, Carsten Michael ; Gerber, Bernd ; Tesch, Hans ; Hirsmüller, Susanne ; Sinn, Hans-Peter ; Dunst, Jürgen ; Münstedt, Karsten ; Bick, Ulrich ; Fallenberg, Eva ; Tholen, Reina ; Hung, Roswita ; Baumann, Freerk T. ; Beckmann, Matthias Wilhelm ; Blohmer, Jens-Uwe ; Fasching, Peter Andreas ; Lux, Michael Patrick ; Harbeck, Nadia ; Hadji, Peyman ; Hauner, Hans ; Heywang-Köbrunner, Sylvia H. ; Huober, Jens ; Hübner, Jutta ; Jackisch, Christian ; Loibl, Sibylle ; Lück, Hans-Jürgen ; Minckwitz, Gunter von ; Möbus, Volker ; Müller, Volkmar ; Nöthlings, Ute ; Schmidt, Marcus ; Schmutzler, Rita Katharina ; Schneeweiss, Andreas ; Schütz, Florian ; Stickeler, Elmar ; Thomssen, Christoph ; Untch, Michael ; Wesselmann, Simone ; Bücker, Arno ; Krockenberger, Mathias Heinric
Ziele: Das Ziel dieser offiziellen Leitlinie, die von der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG) und der Deutschen Krebsgesellschaft (DKG) publiziert und koordiniert wurde, ist es, die Früherkennung, Diagnostik, Therapie und Nachsorge des Mammakarzinoms zu optimieren.
Methoden: Der Aktualisierungsprozess der S3-Leitlinie aus 2012 basierte zum einen auf der Adaptation identifizierter Quellleitlinien und zum anderen auf Evidenzübersichten, die nach Entwicklung von PICO-(Patients/Interventions/Control/Outcome-)Fragen, systematischer Recherche in Literaturdatenbanken sowie Selektion und Bewertung der gefundenen Literatur angefertigt wurden. In den interdisziplinären Arbeitsgruppen wurden auf dieser Grundlage Vorschläge für Empfehlungen und Statements erarbeitet, die im Rahmen von strukturierten Konsensusverfahren modifiziert und graduiert wurden.
Empfehlungen: Der Teil 1 dieser Kurzversion der Leitlinie zeigt Empfehlungen zur Früherkennung, Diagnostik und Nachsorge des Mammakarzinoms: Der Stellenwert des Mammografie-Screenings wird in der aktualisierten Leitlinienversion bestätigt und bildet damit die Grundlage der Früherkennung. Neben den konventionellen Methoden der Karzinomdiagnostik wird die Computertomografie (CT) zum Staging bei höherem Rückfallrisiko empfohlen. Die Nachsorgekonzepte beinhalten Untersuchungsintervalle für die körperliche Untersuchung, Ultraschall und Mammografie, während weiterführende Gerätediagnostik und Tumormarkerbestimmungen bei der metastasierten Erkrankung Anwendung finden.
Wöckel, Achim ; Festl, Jasmin ; Stüber, Tanja ; Brust, Katharina ; Stangl, Stephanie ; Heuschmann, Peter Ulrich ; Albert, Ute Susann ; Budach, Wilfried ; Follmann, Markus ; Janni, Wolfgang ; Kopp, Ina ; Kreienberg, Rolf ; Kühn, Thorsten ; Langer, Thomas ; Nothacker, Monika ; Scharl, Anton ; Schreer, Ingrid ; Link, Hartmut ; Engel, Jutta ; Fehm, Tanja ; Weis, Joachim ; Welt, Anja ; Steckelberg, Anke ; Feyer, Petra ; König, Klaus ; Hahne, Andrea ; Kreipe, Hans H. ; Knoefel, Wolfram Trudo ; Denkinger, Michael ; Brucker, Sara ; Lüftner, Diana ; Kubisch, Christian ; Gerlach, Christina ; Lebeau, Annette ; Siedentopf, Friederike ; Petersen, Cordula ; Bartsch, Hans Helge ; Schulz-Wendtland, Rüdiger ; Hahn, Markus ; Hanf, Volker ; Müller-Schimpfle, Markus ; Henscher, Ulla ; Roncarati, Renza ; Katalinic, Alexander ; Heitmann, Christoph ; Honegger, Christoph ; Paradies, Kerstin ; Bjelic-Radisic, Vesna ; Degenhardt, Friedrich ; Wenz, Frederik ; Rick, Oliver ; Hölzel, Dieter ; Zaiss, Matthias ; Kemper, Gudrun ; Budach, Volker ; Denkert, Carsten Michael ; Gerber, Bernd ; Tesch, Hans ; Hirsmüller, Susanne ; Sinn, Hans-Peter ; Dunst, Jürgen ; Münstedt, Karsten ; Bick, Ulrich ; Fallenberg, Eva ; Tholen, Reina ; Hung, Roswita ; Baumann, Freerk T. ; Beckmann, Matthias Wilhelm ; Blohmer, Jens-Uwe ; Fasching, Peter Andreas ; Lux, Michael Patrick ; Harbeck, Nadia ; Hadji, Peyman ; Hauner, Hans ; Heywang-Köbrunner, Sylvia H. ; Huober, Jens ; Hübner, Jutta ; Jackisch, Christian ; Loibl, Sibylle ; Lück, Hans-Jürgen ; Minckwitz, Gunter von ; Möbus, Volker ; Müller, Volkmar ; Nöthlings, Ute ; Schmidt, Marcus ; Schmutzler, Rita Katharina ; Schneeweiss, Andreas ; Schütz, Florian ; Stickeler, Elmar ; Thomssen, Christoph ; Untch, Michael ; Wesselmann, Simone ; Bücker, Arno ; Krockenberger, Mathias Heinric
Purpose: The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer.
Methods: The process of updating the S3 guideline dating from 2012 was based on the adaptation of identified source guidelines which were combined with reviews of evidence compiled using PICO (Patients/Interventions/Control/Outcome) questions and the results of a systematic search of literature databases and the selection and evaluation of the identified literature. The interdisciplinary working groups took the identified materials as their starting point to develop recommendations and statements which were modified and graded in a structured consensus procedure.
Recommendations: Part 1 of this short version of the guideline presents recommendations for the screening, diagnosis and follow-up care of breast cancer. The importance of mammography for screening is confirmed in this updated version of the guideline and forms the basis for all screening. In addition to the conventional methods used to diagnose breast cancer, computed tomography (CT) is recommended for staging in women with a higher risk of recurrence. The follow-up concept includes suggested intervals between physical, ultrasound and mammography examinations, additional high-tech diagnostic procedures, and the determination of tumor markers for the evaluation of metastatic disease.
Kreuter, Matthias-Heinrich ; Bernd, August ; Holzmann, Hans ; Müller-Klieser, Wolfgang ; Maidhof, Armin ; Weißmann, Norbert ; Kljajić, Zoran ; Batel, Renato ; Schröder, Heinz C. ; Müller, Werner E. G.
(±)-Aeroplysinin-1, an optically active 1.2-dihydroarene-1.2-diol. was isolated from the marine sponges Verongia aerophoba (+-isomer) and lanthella ardis (--isomer). For the experiments presented we used the +-isomer from Verongia aerophoba. Here we describe the hitherto unknown biological and pharmacological property of this compound to display pronounced anticancer activity against L5178y mouse lymphoma cells (ED50: 0.5 μm). Friend erythroleukemia cells (ED50: 0.7μm) , human mamma carcinoma cells (ED50: 0.3μm) and human colon carcinoma cells (ED50: 3.0 μm) in vitro. Furthermore, aeroplysinin caused a preferential inhibition of [3H]thymidine (dThd) incorporation rates in L5178y mouse lymphoma cells if compared with murine spleen lymphocytes in vitro. At concentrations between 1.1 and 28.5 μm, the [3H]dThd incorporation rates in L5178y cells were suppressed to 28% -0% but only to 78% -18% in murine spleen lymphocytes. The same differential effect in vitro was found with the following epithelial cells: 14.70 μm of the compound were required to inhibit normal human fibroblasts to 50% , but only 2.9 μm in the assays with human malign keratinocytes or malignant melanoma cells to observe the same inhibitory effect. Moreover, aeroplysinin-1 displayed antileukemic activity in vivo using the L5178y cell/NMRI mouse system; administered at a dose of 50 mg/kg for five consecutive days, the T/C (% ) value was determined to be 338. Preliminary toxicology studies revealed an acute LD50 of 202 mg/kg and a subacute LD50 of 150 mg/kg. Aeroplysinin-1 is neither a direct mutagen nor a premutagen in the umu/Salmonella typhimurium test system.
Middeke, Jan Moritz ; Metzeler, Klaus Hans ; Röllig, Christoph ; Krämer, Michael ; Eckardt, Jan-Niklas ; Stasik, Sebastian ; Greif, Philipp ; Spiekermann, Karsten ; Rothenberg-Thurley, Maja ; Krug, Utz ; Braess, Jan ; Krämer, Alwin ; Hochhaus, Andreas ; Brümmendorf, Tim Henrik ; Naumann, Ralph ; Steffen, Björn ; Einsele, Hermann ; Schaich, Markus ; Burchert, Andreas ; Neubauer, Andreas ; Görlich, Dennis ; Sauerland, Cristina ; Schäfer-Eckart, Kerstin ; Schliemann, Christoph ; Krause, Stefan W. ; Hänel, Mathias ; Frickhofen, Norbert ; Noppeney, Richard ; Kaiser, Ulrich ; Kaufmann, Martin ; Kunadt, Désirée ; Wörmann, Bernhard ; Sockel, Katja ; Bonin, von Malte ; Herold, Tobias ; Müller-Tidow, Carsten ; Platzbecker, Uwe ; Berdel, Wolfgang E. ; Serve, Hubert ; Baldus, Claudia ; Ehninger, Gerhard ; Schetelig, Johannes ; Hiddemann, Wolfgang ; Bornhäuser, Martin ; Stölzel, Friedrich ; Thiede, Christian
Mutations of the isocitrate dehydrogenase-1 (IDH1) and IDH2 genes are among the most frequent alterations in acute myeloid leukemia (AML) and can be found in ∼20% of patients at diagnosis. Among 4930 patients (median age, 56 years; interquartile range, 45-66) with newly diagnosed, intensively treated AML, we identified IDH1 mutations in 423 (8.6%) and IDH2 mutations in 575 (11.7%). Overall, there were no differences in response rates or survival for patients with mutations in IDH1 or IDH2 compared with patients without mutated IDH1/2. However, distinct clinical and comutational phenotypes of the most common subtypes of IDH1/2 mutations could be associated with differences in outcome. IDH1-R132C was associated with increased age, lower white blood cell (WBC) count, less frequent comutation of NPM1 and FLT3 internal tandem mutation (ITD) as well as with lower rate of complete remission and a trend toward reduced overall survival (OS) compared with other IDH1 mutation variants and wild-type (WT) IDH1/2. In our analysis, IDH2-R172K was associated with significantly lower WBC count, more karyotype abnormalities, and less frequent comutations of NPM1 and/or FLT3-ITD. Among patients within the European LeukemiaNet 2017 intermediate- and adverse-risk groups, relapse-free survival and OS were significantly better for those with IDH2-R172K compared with WT IDH, providing evidence that AML with IDH2-R172K could be a distinct entity with a specific comutation pattern and favorable outcome. In summary, the presented data from a large cohort of patients with IDH1/2 mutated AML indicate novel and clinically relevant findings for the most common IDH mutation subtypes.
Lux, Michael Patrick ; Nabieva, Naiba ; Hartkopf, Andreas ; Huober, Jens ; Volz, Bernhard ; Ţăran, Florin-Andrei ; Overkamp, Friedrich ; Kolberg, Hans-Christian ; Hadji, Peyman ; Tesch, Hans ; Häberle, Lothar ; Ettl, Johannes ; Lüftner, Diana ; Wallwiener, Markus ; Müller, Volkmar ; Beckmann, Matthias Wilhelm ; Belleville, Erik ; Wimberger, Pauline ; Hielscher, Carsten ; Geberth, Matthias ; Abenhardt, Wolfgang ; Kurbacher, Christian M. ; Würstlein, Rachel ; Thomssen, Christoph ; Untch, Michael ; Fasching, Peter Andreas ; Janni, Wolfgang ; Fehm, Tanja ; Wallwiener, Diethelm ; Schneeweiss, Andreas ; Brucker, Sara
This study presents comprehensive real-world data on the use of anti-human epidermal growth factor receptor 2 (HER2) therapies in patients with HER2-positive metastatic breast cancer (MBC). Specifically, it describes therapy patterns with trastuzumab (H), pertuzumab + trastuzumab (PH), lapatinib (L), and trastuzumab emtansine (T-DM1). The PRAEGNANT study is a real-time, real-world registry for MBC patients. All therapy lines are documented. This analysis describes the utilization of anti-HER2 therapies as well as therapy sequences. Among 1936 patients in PRAEGNANT, 451 were HER2-positive (23.3%). In the analysis set (417 patients), 53% of whom were included in PRAEGNANT in the first-line setting, 241 were treated with H, 237 with PH, 85 with L, and 125 with T-DM1 during the course of their therapies. The sequence PH → T-DM1 was administered in 51 patients. Higher Eastern Cooperative Oncology Group (ECOG) scores, negative hormone receptor status, and visceral or brain metastases were associated with more frequent use of this therapy sequence. Most patients received T-DM1 after treatment with pertuzumab. Both novel therapies (PH and T-DM1) are utilized in a high proportion of HER2-positive breast cancer patients. As most patients receive T-DM1 after PH, real-world data may help to clarify whether the efficacy of this sequence is similar to that in the approval study.
Hans Joachim Schädlich ist einer der renommiertesten, literarisch bedeutendsten Autoren aus dem Kreis derer, die seit 1976 die DDR verließen. Er war ein Schriftsteller, den man nicht veröffentlichen ließ, und ein bekennender Demokrat, der alle Vorstellungen seiner Intellektuellen-Kollegen, den "realen Sozialismus" vielleicht doch noch reformieren und zum "wahren Sozialismus" machen zu können, für illusionär hielt. Der Gang der deutschen Dinge seit 1989 hat ihn ohne Einschränkung bestätigt. Zur DDR-Literatur wollte und will Schädlich eigentlich nicht gehören - und muß es doch hinnehmen, wenn er zumindest partiell in Kontexten von DDR-Literatur gesehen und analysiert wird, ohne daß jemand auf die Idee käme, seine Texte mit denen von Hermann Kant und Erik Neutsch, ja, nicht einmal mit denen von Christa Wolf und Volker Braun in eins zu setzen.
Continuous blood glucose monitoring reveals enormous circadian variations in pregnant diabetic rats
(2018)
Golic, Michaela ; Kräker, Kristin ; Fischer, Caroline ; Alenina, Natalia ; Haase, Nadine ; Herse, Florian ; Schütte, Till ; Henrich, Wolfgang ; Müller, Dominik N. ; Busjahn, Andreas ; Bader, Michael ; Dechend, Ralf
Aim: Diabetes in pregnancy is a major burden with acute and long-term consequences. Its treatment requires adequate diagnosis and monitoring of therapy. Many experimental research on diabetes during pregnancy has been performed in rats. Recently, continuous blood glucose monitoring of non-pregnant diabetic rats revealed an increased circadian variability of blood glucose that made a single blood glucose measurement per day inappropriate to reflect glycemic status. Continuous blood glucose measurement has never been performed in pregnant rats. We wanted to perform continuous blood glucose monitoring in pregnant rats to decipher the influence of pregnancy on blood glucose in diabetic and normoglycemic status.
Methods: We used the transgenic Tet29 diabetes rat model with an inducible knock down of the insulin receptor via RNA interference upon application of doxycycline (DOX) leading to insulin resistant type II diabetes. All Tet29 rats received a HD-XG telemetry implant (Data Sciences International, USA) that measured blood glucose and activity continuously. Rats were divided into four groups and blood glucose was monitored until end of pregnancy or the corresponding period: Tet29 + DOX (diabetic) non-pregnant, Tet29 + DOX (diabetic) pregnant, Tet29 (normoglycemic) non-pregnant, Tet29 (normoglycemic) pregnant.
Results: All analyzed rats displayed a circadian variation in blood glucose concentration. Circadian variability was much more pronounced in pregnant diabetic rats than in normoglycemic pregnant rats. Pregnancy ameliorated variation in blood glucose in diabetic situation. Pregnancy continuously decreased blood glucose during normoglycemic pregnancy. Diabetic rats were less active than normoglycemic rats. We performed a calculation showing that application of continuous blood glucose measurement reduces animal numbers needed to detect a given effect in experimental setting by decreasing variability and SD.
Interpretation: Continuous blood glucose monitoring via a telemetry device in pregnant rats provides a more informative picture of the glycemic situation in comparison to single measurements. This could improve diagnosis and therapy of diabetes, decrease animal numbers within experimental settings, and add another physiological parameter (activity) to the analysis that could be helpful in testing therapeutic concepts targeting blood glucose levels and peripheral muscle function. We propose continuous glucose monitoring as a new tool for the evaluation of pregnant diabetic rats.