160 research outputs found
Ville de sable. Projet de Killoffer et Senges
No full textMaterials such as asphalt, steel, cement, glass interact with the space producing it or transforming it. Launched a critical look at Montesquieu's Lettres persanes, the project of urbanism in the making, developed by the author Pierre Senges and by illustrator Killoffer, puts it to the test the tightness of the sand. Controversial element in architecture because of its brittleness, could it support the writing of a city? This study questions the nodes Géométrie dans la poussière (Verticales, 2004), a work in which the relationship between geology and geometry generates a model phased, dismantling the utopian temptations without being absorbed nor the exotic nor the descriptive
ein Konzept zur Optimierung und Vernetzung der prä- und inhospitalen Therapie ; Erfahrungen und Ergebnisse aus den Jahren 1999 - 2001
No full textAnfang der 90er Jahre entwickelten sich neue pharmakologische Behandlungsstrategien des akuten Myokardinfarktes durch GP IIb/IIIa- Rezeptorantagonisten. Der optimale Zeitpunkt der Administration und die Wahl des Therapieregimes ist Diskussionsstoff. Ziel dieses Konzeptes ist es, mit der Verlagerung des Therapiebeginns in die Prähospitalphase die Zeit bis zur Reperfusion des Infarktareals zu minimieren. Die Schaffung einer Hotline zum Kardiologen bietet dem Notarzt fachlichen Rat. Bestehen keine logistischen Hindernisse innerhalb von 60 Minuten wird eine Herzkatheteruntersuchung, bei Überschreiten wird die Kombinationslysetherapie mit interventioneller Versorgung des Infarktgefäßes binnen 24 Stunden durchgeführt. Ziel der Datenanalyse war nachzuweisen, ob die Sterblichkeit von bis zu 15% im Vergleich zu Registerstudien gleicher Konzeption niedriger und die Krankenhausverweildauer von 12 Tagen kürzer ist. Im Erfassungszeitraum wurden 347 Patienten, davon 254 Männer (73%) und 93 Frauen (27%) behandelt. Das Alter im Median betrug 62 Jahre. 57 (16%) Patienten wurden prähospital lysiert, 81 (20%) inhospital. 218 (63%) wurden mittels primärer interventioneller Therapie behandelt. Die Aufenthaltsdauer im Krankenhaus aller Patienten betrug 6 Tage. Der Aufenthalt im Median auf der Intensivstation betrug in der Gruppe der lysierten Patienten 1,0 Tage (prähospital 0,8 vs inhospital 1,3 Tage), in der primären Herzkathetergruppe 0,9 Tage. 8 MACE traten auf. Die Kankenhausmortalität betrug 6,3 %, in der Gruppe der mittels Lyse behandelten Patienten 9,3% (prähospital 12,3%, inhospital 6,9%) und in der primär interventionell versorgten Gruppe 4,6%. Die Mortalität der initial hämodynamisch stabilen Patienten lag unter 3%. Die 180 Tage Mortalität betrug gesamt 10,8%, in der Lyse Gruppe 11,7% (prähospital 14,0% vs. inhospital 9,9%) und 9,2% in der interventionell behandelten Gruppe. Zu keinem Zeitpunkt bestanden signifikante Unterschiede. Die aggressive Therapie des akuten Myokardinfarkts beinhaltet diesen Daten zufolge kein Risiko für die Patienten und zeigt im Vergleich zu Registerstudien ähnlicher Konzeption eine niedrigere Krankenhaussterblichkeit und eine kürzere Krankenhausverweildauer. Diese Arbeit ist der Erinnerung an meinem geschätzten Freund und Kollegen Oberarzt Dr. med. Torsten Thieme gewidmet, der viel zu früh verstorben ist.In the early 90’s a new class of agents blocking the GPIIb/IIIa-receptors on the platelet surface was developed capable of speeding up pharmacological reopening of infarct related arteries. The optimal time of administration remains subject of discussion. Despite these advantages hospital mortality in great registries is still more than 15% and hospital stay 12 days. By January 1st, 1999 a hotline between ambulance car and the interventional cardiologist was instituted. In each case management with either immediate PCI under GPIIb/IIIa-inhibition or half dose thrombolytics and full dose GPIIb/IIIa-inhibitors, if possible, started out of hospital. The approach was to see if the mortality was lower and the hospital stay shorter than in comparable registries. During September 1999 – December 2001 347 patients aged 26 to 92 years (60 plus minus 13) were treated. Median age was 62 years. There were 93 female (27%) and 254 male patients (73%). 57 (16%) patients received out of hospital thrombolysis, 81 (20%) were treated inhospital and 218 (63%) patients underwent primary cardiac catheterization. Overall inhospital median stay was 6.0 days. The median ICU-time for all thrombolysed patient was 1,0 days (prehospital 0,8 vs inhospital 1,3 days) and in the interventionally treated group 0,9 days. In all patients .8 MACE events occurred. Overall hospital mortality was 6,3 %, in the group of thrombolysed patients 9,3% (prehospital 12,3%, inhospital 6,9%). Shock excluded mortality was below 3%. 346/347 patients reached 180 days of follow-up. 180 days mortality overall was 10,8%, for the thrombolysed group 11,7% (prehospital 14,0% vs. inhospital 9,9%) and 9,2% in the interventionally treated group. There was no statistical significant difference. The time optimized individualized treatment assignment to pharmacological therapy followed by routine facilitated PCI within 24 hours is an approach that is more aggressive than currently recommended in the guidelines, but seems to offer further improvements of outcome with no further riscs for patients with AMI in comparison to other registries. This work is published in memory of my beloved friend and colleague Torsten Thieme, MD, who died much to young
Percutaneous mitral valve repair with the MitraClip system according to predicted risk by logistic EuroSCORE: first results from the German Mitral Valve registry
No full textComparison of Proteomic Responses
No full textTo support antibiotic mechanism of action characterization we developed an approach to compare the proteomic responses of bacteria to sublethal doses of antibiotics, called Comparison of Proteomic Responses (CoPR). Through comparison of profiles of known and unknown mechanisms, this approach allows rapid distinction between antibiotics of precedent and unprecedent mechanisms of action. The python script provided here shall simplify the calculation of CoPR scores, which allow the comparison of proteomic responses. Using an excel library (.xslx) of upregulated marker proteins from B. subtilis or P. aeruginosa as input, CoPR.py generates a similarity matrix as an .csv output and a visualization of response similarities using t-distributed stochastic neighbor embedding.The script works with Python 3 (3.8), matplotlib (3.3.4), numpy (1.20.1), pandas (1.2.2), scikit-learn (0.24.1), and openpyxl (3.0.6).
The approach was first described in Senges CHR, Stepanek JJ, Wenzel M, Raatschen N, Ay Ü, Märtens Y, Prochnow P, Vázquez Hernández M, Yayci A, Schubert B, Janzing NBM, Warmuth HL, Kozik M, Bongard J, Alumasa JN, Albada B, Penkova M, Lukežič T, Sorto NA, Lorenz N, Miller RG, Zhu B, Benda M, Stülke J, Schäkermann S, Leichert LI, Scheinpflug K, Brötz-Oesterhelt H, Hertweck C, Shaw JT, Petković H, Brunel JM, Keiler KC, Metzler-Nolte N, Bandow JE. 2021. Comparison of proteomic responses as global approach to antibiotic mechanism of action elucidation. Antimicrob Agents Chemother 65:e01373-20. https://doi.org/10.1128/AAC.01373-20.
The python script was first described in Yayci A, Schäkermann S, Berscheid A, Oesterhelt F, Miess H, Senges CHR, Gross H, Klöckner A, Schneider T, Brötz-Oesterhelt H, Bandow JE. 2021. The lipopeptide brabantamide A impairs cell envelop integrity in Gram-positive bacteria TBD.
The data collected in the libraries (Excel-files) originate from a variety of publications:
Bacillus subtilis:
Eymann C, Homuth G, Scharf C, Hecker M. 2002 Bacillus subtilis functional genomics: global characterization of the stringent response by proteome and transcriptome analysis. J. Bacteriol. 184:2500–2520 https://doi.org/10.1016/j.bbamem.2015.11.009
Bandow JE, Brötz H, Leichert LI, Labischinski H, Hecker M. 2003. Proteomic approach to understanding antibiotic action. 2003. Antimicrob. Agents Chemother. 47:948–955. https://doi.org/10.1128/aac.47.3.948-955.2003
Sender U, Bandow J, Engelmann S, Lindequist U, Hecker M. 2004. Proteomic signatures for daunomycin and adriamycin in Bacillus subtilis. 2004. Die Pharmazie 59:65–70
Brötz-Oesterhelt H, Beyer D, Kroll H-P, Endermann R, Ladel C, Schroeder W, Hinzen B, Raddatz S, Paulsen H, Henninger K, Bandow JE, Sahl H-G, Labischinski H. 2005. Dysregulation of bacterial proteolytic machinery by a new class of antibiotics. Nat. Med. 11, 1082–1087. https://doi.org/10.1038/nm1306
Wenzel M, Patra M, Albrecht D, Chen DY-K, Nicolaou KC, Metzler-Nolte N, Bandow JE. 2011. Proteomic signature of fatty acid biosynthesis inhibition available for in vivo mechanism-of-action studies. Antimicrob. Agents Chemother. 55:2590–2596 https://doi.org/10.1128/aac.00078-11
Wenzel M, Kohl B, Münch D, Raatschen N, Albada HB, Hamoen L, Metzler-Nolte N, Sahl H-G, Bandow JE. 2012 Proteomic response of Bacillus subtilis to lantibiotics reflects differences in interaction with the cytoplasmic membrane. Antimicrob. Agents Chemother. 56:5749–5757 https://doi.org/10.1128/aac.01380-12
Raatschen N, Wenzel M, Leichert LIO, Düchting P, Krämer U, Bandow JE. 2013. Extracting iron and manganese from bacteria with ionophores - a mechanism against competitors characterized by increased potency in environments low in micronutrients. Proteomics 13:1358–1370 https://doi.org/10.1002/pmic.201200556
Wenzel M, Patra M, Senges CHR, Ott I, Stepanek JJ, Pinto A, Prochnow P, Vuong C, Langklotz S, Metzler-Nolte N, Bandow JE. 2013. Analysis of the mechanism of action of potent antibacterial hetero-tri-organometallic compounds: a structurally new class of antibiotics. ACS chemical biology 8:1442–1450 https://doi.org/10.1021/cb4000844
Wenzel M, Chiriac AI, Otto A, Zweytick D, May C, Schumacher C, Gust R, Albada HB, Penkova M, Krämer U, Erdmann R, Metzler-Nolte N, Straus SK, Bremer E, Becher D, Brötz-Oesterhelt H, Sahl H-G, Bandow JE. 2014 Small cationic antimicrobial peptides delocalize peripheral membrane proteins. Proc. Natl. Acad. Sci. USA 111:E1409-E1418 https://doi.org/10.1073/pnas.1319900111
Münch D, Müller A, Schneider T, Kohl B, Wenzel M, Bandow JE, Maffioli S, Sosio M, Donadio S, Wimmer R, Sahl H-G. 2014. The lantibiotic NAI-107 binds to bactoprenol-bound cell wall precursors and impairs membrane functions. J. Biol. Chem. 289:12063–12076 https://doi.org/10.1074/jbc.m113.537449
Wenzel M, Senges CHR, Zhang J, Suleman S, Nguyen M, Kumar P, Chiriac AI, Stepanek JJ, Raatschen N, May C, Krämer U, Sahl H-G, Straus SK, Bandow JE. 2015. Antimicrobial peptides from the aurein family form ion-selective pores in Bacillus subtilis. ChemBioChem 16:1101–1108. https://doi.org/10.1002/cbic.201500020
Wenzel M, Schriek P, Prochnow P, Albada HB, Metzler-Nolte N, Bandow JE. 2016. Influence of lipidation on the mode of action of a small RW-rich antimicrobial peptide. BBA - Biomembranes 1858:004–1011 https://doi.org/10.1016/j.bbamem.2015.11.009
Stepanek JJ, Schäkermann S, Wenzel M, Prochnow P, Bandow JE. 2016. Purine biosynthesis is the bottleneck in trimethoprim-treated Bacillus subtilis. Proteomics. Clin. Appl. 10:1036–1048 https://doi.org/10.1002/prca.201600039
Stepanek JJ, Lukežič T, Teichert I, Petković H, Bandow JE, Dual mechanism of action of the atypical tetracycline chelocardin. 2016. BBA - Proteins and Proteomics 1864:645–654 https://doi.org/10.1016/j.bbapap.2016.03.004
Müller A, Wenzel M, Strahl H, Grein F, Saaki TNV, Kohl B, Siersma T, Bandow JE, Sahl H-G, Schneider T, Hamoen LW. 2016. Daptomycin inhibits cell envelope synthesis by interfering with fluid membrane microdomains. Proc. Natl. Acad. Sci USA 113:E7077-E7086 https://doi.org/10.1073/pnas.1611173113
Scheinpflug K, Wenzel M, Krylova O, Bandow JE, Dathe M, Strahl H. Antimicrobial peptide cWFW kills by combining lipid phase separation with autolysis. 2017. Sci. Rep. 7:44332 https://doi.org/10.1038/srep44332
Saising J, Nguyen M-T, Härtner T, Ebner P, Bhuyan AAM, Berscheid A, Muehlenkamp M, Schäkermann S, Kumari N, Maier ME, Voravuthikunchai SP, Bandow J, Lang F, Brötz-Oesterhelt H, Götz F. 2018. Rhodomyrtone (Rom) is a membrane-active compound. BBA - Biomembranes 1860:1114–1124 https://doi.org/10.1016/j.bbamem.2018.01.011
Meier D, Vázquez Hernández M, van Geelen L, Muharini R, Proksch P, Bandow JE, Kalscheuer R. 2019. The plant-derived chalcone Xanthoangelol targets the membrane of Gram-positive bacteria. Bioorg Med Chem. 27:115151 https://doi.org/10.1016/j.bmc.2019.115151
Wüllner D, Haupt A, Prochnow P, Leontiev R, Slusarenko AJ, Bandow JE. 2019 Interspecies comparison of the bacterial response to allicin reveals species-specific defense strategies. Proteomics 19:1900064(1-12). https://doi.org/10.1002/pmic.201900064
Senges CHR, Stepanek JJ, Wenzel M, Raatschen N, Ay Ü, Märtens Y, Prochnow P, Vázquez Hernández M, Yayci A, Schubert B, Janzing NBM, Warmuth HL, Kozik M, Bongard J, Alumasa JN, Albada B, Penkova M, Lukežič T, Sorto NA, Lorenz N, Miller RG, Zhu B, Benda M, Stülke J, Schäkermann S, Leichert LI, Scheinpflug K, Brötz-Oesterhelt H, Hertweck C, Shaw JT, Petković H, Brunel JM, Keiler KC, Metzler-Nolte N, Bandow JE. 2021. Comparison of proteomic responses as global approach to antibiotic mechanism of action elucidation. Antimicrob Agents Chemother 65:e01373-20. https://doi.org/10.1128/AAC.01373-20.
Yayci A, Schäkermann S, Berscheid A, Oesterhelt F, Miess H, Senges CHR, Gross H, Klöckner A, Schneider T, Brötz-Oesterhelt H, Bandow JE. 2021. The lipopeptide brabantamide A impairs cell envelop integrity in Gram-positive bacteria TBD.
Pseudomonas aeruginosa:
Wüllner D, Haupt A, Prochnow P, Leontiev R, Slusarenko AJ, Bandow JE. 2019 Interspecies comparison of the bacterial response to allicin reveals species-specific defense strategies. Proteomics 19:1900064(1-12). https://doi.org/10.1002/pmic.201900064
Wüllner D, Thomsen J, Gesper M, Haupt A, Zhoud P, Narberhaus F, Bandow JE. 2021. Proteomic response of Pseudomonas aeruginosa to antibiotic treatment. TBD.
We gratefully acknowledge funding from the German Research Foundation (BA 4193/6-1); the German Federal State of North Rhine-Westphalia for the mass spectrometer (Forschungsgroßgeräte der Länder); NRW grant Translation of Innovative Antibiotics; the German Federal State of North Rhine-Westphalia and the European Union, European Regional Development Fund, Investing in Your Future (Innovative Antibiotics from NRW and the Research Infrastructure Center for System-Based Antibiotic Research [CESAR])
Comparative cost-effectiveness analyses of cardiovascular magnetic resonance and coronary angiography combined with fractional flow reserve for the diagnosis of coronary artery disease.
No full textAccording to recent guidelines, patients with coronary artery disease (CAD) should undergo revascularization if significant myocardial ischemia is present. Both, cardiovascular magnetic resonance (CMR) and fractional flow reserve (FFR) allow for a reliable ischemia assessment and in combination with anatomical information provided by invasive coronary angiography (CXA), such a work-up sets the basis for a decision to revascularize or not. The cost-effectiveness ratio of these two strategies is compared
Percutaneous mitral valve repair with the MitraClip system according to predicted risk by logistic EuroSCORE: first results from the German Mitral Valve registry
No full text
Clinical effects of long-term cardiac contractility modulation (CCM) in subjects with heart failure caused by left ventricular systolic dysfunction
No full textINTRODUCTION: Heart failure is a major cause of morbidity and mortality throughout the world. Despite advances in therapy, nearly half of patients receiving guideline-directed medical therapy remain limited by symptoms. Cardiac contractility modulation (CCM) can improve symptoms in this population, but efficacy and safety in prospective studies has been limited to 12 months of follow-up. We report on the first 2 year multi-site evaluation of CCM in patients with heart failure. METHODS: One hundred and forty-three subjects with heart failure and reduced ejection fraction were followed via clinical registry for 24 months recording NYHA class, MLWHFQ score, 6 min walk distance, LVEF, and peak VO2 at baseline and 6 month intervals as clinically indicated. Serious adverse events, and all cause as well as cardiovascular mortality were recorded. Data are presented stratified by LVEF (all subjects, LVEF <35%, LVEF ≥35%). RESULTS: One hundred and six subjects from 24 sites completed the 24 month follow-up. Baseline parameters were similar among LVEF groups. NYHA and MLWHFQ improved in all 3 groups at each time point. LVEF in the entire cohort improved 2.5, 2.9, 5.0, and 4.9% at 6, 12, 18, and 24 months, respectively. Insufficient numbers of subjects had follow-up data for 6 min walk or peak VO2 assessment, precluding comparative analysis. Serious adverse events (n = 193) were observed in 91 subjects and similarly distributed between groups with LVEF <35% and LVEF ≥35%, and similar to other device trials for heart failure. Eighteen deaths (7 cardiovascularly related) over 2 years. Overall survival at 2 years was 86.4% (95% confidence intervals: 79.3, 91.2%). CONCLUSION: Cardiac contractility modulation provides safe and effective long-term symptomatic and functional improvement in heart failure. These benefits were independent of baseline LVEF and were associated with a safety profile similar to published device trials
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