61 results on '"Rosenberger, Peter"'
Search Results
2. Characterization of Shear Stress Mediated Platelet Dysfunction: Data from an Ex Vivo Model for Extracorporeal Circulation and a Prospective Clinical Study
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Hidiatov, Oleg, Gaupp, Alisha, Marini, Irene, Pelzl, Lisann, Wagner, Miriam, Rigoni, Flavianna, Witzemann, Andreas, Häberle, Helene, Martus, Peter, Ngamsri, Kristian-Christos, Konrad, Franziska M., Rosenberger, Peter, Straub, Andreas, Bakchoul, Tamam, and Althaus, Karina
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- 2023
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3. Blutungsrisiko im Kanülenbereich bei physiotherapeutischer Mobilisation unter extrakorporaler Membranoxygenierung
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Baasner, Ann-Kathrin, Koeppen, Michael, and Rosenberger, Peter
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Hintergrund: Patient*innen, die an einem akuten Atemnotsyndrom leiden, erhalten als letztmögliche Therapie eine extrakorporale Membranoxygenierung (ECMO). Am Universitätsklinikum Tübingen werden diese Patient*innen während dieser Phase durch ein speziell geschultes Team physiotherapeutisch behandelt, um einer körperlichen Dekonditionierung entgegenzuwirken. Ziel der Arbeit: In dieser Arbeit wurde das Risiko einer Blutung im Bereich der Kanüleneinstichstelle während der physiotherapeutischen Mobilisation untersucht und eine Einschätzung der Sicherheitsaspekte beschrieben. Methodik: Auf der anästhesiologischen Intensivstation des Universitätsklinikums Tübingen wurden in dem Zeitraum von 2013–2018 n= 83 Patient*innen behandelt, die den Einschlusskriterien entsprachen. Die Datensätze wurden mittels einer Fall-Kontroll-Studie retrospektiv analysiert. Die Patient*innen wurden nach ihrem erreichten Mobilisationsstand in eine passive Kontrollgruppe und in eine aktive Interventionsgruppe unterteilt. Blutungsereignisse, Implantationsdauer der ECMO und weitere Aspekte wurden in dieser Analyse besonders betrachtet. Ergebnisse und Schlussfolgerung: Es traten sowohl in der passiven als auch in der aktiven Gruppe jeweils 2 Blutungsereignisse auf, die jedoch nicht im Zusammenhang mit der physiotherapeutischen Mobilisation standen. Die Implantationsdauer der ECMO variiert insgesamt zwischen einem und 77 Tagen. Eine physiotherapeutische Mobilisation durch ein speziell geschultes Team erhöhte das Blutungsrisiko im Kanülenbereich nicht.
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- 2023
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4. Preexisting comorbidities shape the immune response associated with severe COVID-19.
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Kreutmair, Stefanie, Kauffmann, Manuel, Unger, Susanne, Ingelfinger, Florian, Núñez, Nicolás Gonzalo, Alberti, Chiara, De Feo, Donatella, Krishnarajah, Sinduya, Friebel, Ekaterina, Ulutekin, Can, Babaei, Sepideh, Gaborit, Benjamin, Lutz, Mirjam, Jurado, Nicole Puertas, Malek, Nisar P., Göpel, Siri, Rosenberger, Peter, Häberle, Helene A., Ayoub, Ikram, and Al-Hajj, Sally
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Comorbidities are risk factors for development of severe coronavirus disease 2019 (COVID-19). However, the extent to which an underlying comorbidity influences the immune response to severe acute respiratory syndrome coronavirus 2 remains unknown. Our aim was to investigate the complex interrelations of comorbidities, the immune response, and patient outcome in COVID-19. We used high-throughput, high-dimensional, single-cell mapping of peripheral blood leukocytes and algorithm-guided analysis. We discovered characteristic immune signatures associated not only with severe COVID-19 but also with the underlying medical condition. Different factors of the metabolic syndrome (obesity, hypertension, and diabetes) affected distinct immune populations, thereby additively increasing the immunodysregulatory effect when present in a single patient. Patients with disorders affecting the lung or heart, together with factors of metabolic syndrome, were clustered together, whereas immune disorder and chronic kidney disease displayed a distinct immune profile in COVID-19. In particular, severe acute respiratory syndrome coronavirus 2–infected patients with preexisting chronic kidney disease were characterized by the highest number of altered immune signatures of both lymphoid and myeloid immune branches. This overall major immune dysregulation could be the underlying mechanism for the estimated odds ratio of 16.3 for development of severe COVID-19 in this burdened cohort. The combinatorial systematic analysis of the immune signatures, comorbidities, and outcomes of patients with COVID-19 has provided the mechanistic immunologic underpinnings of comorbidity-driven patient risk and uncovered comorbidity-driven immune signatures. [Display omitted] [ABSTRACT FROM AUTHOR]
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- 2022
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5. Association of Three-Dimensional Mesh-Derived Right Ventricular Strain with Short-Term Outcomes in Patients Undergoing Cardiac Surgery
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Keller, Marius, Heller, Tim, Duerr, Marcia-Marleen, Schlensak, Christian, Nowak-Machen, Martina, Feng, You-Shan, Rosenberger, Peter, and Magunia, Harry
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Three-dimensional (3D) right ventricular (RV) strain analysis is not routinely performed perioperatively. Although 3D RV strain adds incrementally to outcome prediction in various cardiac diseases, its role in the perioperative setting is not sufficiently understood. The aim of this study was to investigate the association between 3D RV strain measured on RV meshes created from 3D transesophageal echocardiographic data and short-term outcomes among patients undergoing cardiac surgery.
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- 2022
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6. Upregulation of cAMP prevents antibody-mediated thrombus formation in COVID-19
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Zlamal, Jan, Althaus, Karina, Jaffal, Hisham, Häberle, Helene, Pelzl, Lisann, Singh, Anurag, Witzemann, Andreas, Weich, Karoline, Bitzer, Michael, Malek, Nisar, Göpel, Siri, Bösmüller, Hans, Gawaz, Meinrad, Mirakaj, Valbona, Rosenberger, Peter, and Bakchoul, Tamam
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Thromboembolic events are frequently reported in patients infected with the SARS-CoV-2 virus. The exact mechanisms of COVID-19-associated hypercoagulopathy, however, remain elusive. Recently, we observed that platelets (PLTs) from patients with severe COVID-19 infection express high levels of procoagulant markers, which were found to be associated with increased risk for thrombosis. In the current study, we investigated the time course as well as the mechanisms leading to procoagulant PLTs in COVID-19. Our study demonstrates the presence of PLT-reactive IgG antibodies that induce marked changes in PLTs in terms of increased inner-mitochondrial transmembrane potential (Δψ) depolarization, phosphatidylserine (PS) externalization, and P-selectin expression. The IgG-induced procoagulant PLTs and increased thrombus formation were mediated by ligation of PLT Fc-γ RIIA (FcγRIIA). In addition, contents of calcium and cyclic-adenosine-monophosphate (cAMP) in PLTs were identified to play a central role in antibody-induced procoagulant PLT formation. Most importantly, antibody-induced procoagulant events, as well as increased thrombus formation in severe COVID-19, were inhibited by Iloprost, a clinically approved therapeutic agent that increases the intracellular cAMP levels in PLTs. Our data indicate that upregulation of cAMP could be a potential therapeutic target to prevent antibody-mediated coagulopathy in COVID-19 disease.
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- 2022
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7. Upregulation of cAMP prevents antibody-mediated thrombus formation in COVID-19
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Zlamal, Jan, Althaus, Karina, Jaffal, Hisham, Häberle, Helene, Pelzl, Lisann, Singh, Anurag, Witzemann, Andreas, Weich, Karoline, Bitzer, Michael, Malek, Nisar, Göpel, Siri, Bösmüller, Hans, Gawaz, Meinrad, Mirakaj, Valbona, Rosenberger, Peter, and Bakchoul, Tamam
- Abstract
Thromboembolic events are frequently reported in patients infected with the SARS-CoV-2 virus. The exact mechanisms of COVID-19-associated hypercoagulopathy, however, remain elusive. Recently, we observed that platelets (PLTs) from patients with severe COVID-19 infection express high levels of procoagulant markers, which were found to be associated with increased risk for thrombosis. In the current study, we investigated the time course as well as the mechanisms leading to procoagulant PLTs in COVID-19. Our study demonstrates the presence of PLT-reactive IgG antibodies that induce marked changes in PLTs in terms of increased inner-mitochondrial transmembrane potential (Δψ) depolarization, phosphatidylserine (PS) externalization, and P-selectin expression. The IgG-induced procoagulant PLTs and increased thrombus formation were mediated by ligation of PLT Fc-γ RIIA (FcγRIIA). In addition, contents of calcium and cyclic-adenosine-monophosphate (cAMP) in PLTs were identified to play a central role in antibody-induced procoagulant PLT formation. Most importantly, antibody-induced procoagulant events, as well as increased thrombus formation in severe COVID-19, were inhibited by Iloprost, a clinically approved therapeutic agent that increases the intracellular cAMP levels in PLTs. Our data indicate that upregulation of cAMP could be a potential therapeutic target to prevent antibody-mediated coagulopathy in COVID-19 disease.
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- 2022
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8. Severe SARS-CoV-2 Infection Inhibits Fibrinolysis Leading to Changes in Viscoelastic Properties of Blood Clot: A Descriptive Study of Fibrinolysis in COVID-19
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Hammer, Stefanie, Häberle, Helene, Schlensak, Christian, Bitzer, Michael, Malek, Nisar P., Handgretinger, Rupert, Lang, Peter, Hörber, Sebastian, Peter, Andreas, Martus, Peter, Mirakaj, Valbona, Gawaz, Meinrad, Geisler, Tobias, Althaus, Karina, Rosenberger, Peter, and Bakchoul, Tamam
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- 2021
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9. The use of IV immunoglobulin in the treatment of vaccine-induced immune thrombotic thrombocytopenia
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Uzun, Günalp, Althaus, Karina, Singh, Anurag, Möller, Peter, Ziemann, Ulf, Mengel, Annerose, Rosenberger, Peter, Guthoff, Martina, Petzold, Gabor C., Müller, Jens, Büchsel, Martin, Feil, Katharina, Henkes, Hans, Heyne, Nils, Maschke, Matthias, Limpach, Caroline, Nagel, Simon, Sachs, Ulrich J., Fend, Falko, and Bakchoul, Tamam
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- 2021
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10. The use of IV immunoglobulin in the treatment of vaccine-induced immune thrombotic thrombocytopenia
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Uzun, Günalp, Althaus, Karina, Singh, Anurag, Möller, Peter, Ziemann, Ulf, Mengel, Annerose, Rosenberger, Peter, Guthoff, Martina, Petzold, Gabor C., Müller, Jens, Büchsel, Martin, Feil, Katharina, Henkes, Hans, Heyne, Nils, Maschke, Matthias, Limpach, Caroline, Nagel, Simon, Sachs, Ulrich J., Fend, Falko, and Bakchoul, Tamam
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- 2021
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11. Antibody-induced procoagulant platelets in severe COVID-19 infection
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Althaus, Karina, Marini, Irene, Zlamal, Jan, Pelzl, Lisann, Singh, Anurag, Häberle, Helene, Mehrländer, Martin, Hammer, Stefanie, Schulze, Harald, Bitzer, Michael, Malek, Nisar, Rath, Dominik, Bösmüller, Hans, Nieswandt, Bernard, Gawaz, Meinrad, Bakchoul, Tamam, and Rosenberger, Peter
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The pathophysiology of COVID-19–associated thrombosis seems to be multifactorial. We hypothesized that COVID-19 is accompanied by procoagulant platelets with subsequent alteration of the coagulation system. We investigated depolarization of mitochondrial inner transmembrane potential (ΔΨm), cytosolic calcium (Ca2+) concentration, and phosphatidylserine (PS) externalization. Platelets from COVID-19 patients in the intensive care unit (ICU; n = 21) showed higher ΔΨm depolarization, cytosolic Ca2+, and PS externalization compared with healthy controls (n = 18) and non-ICU COVID-19 patients (n = 4). Moreover, significant higher cytosolic Ca2+and PS were observed compared with a septic ICU control group (ICU control; n = 5). In the ICU control group, cytosolic Ca2+and PS externalization were comparable with healthy controls, with an increase in ΔΨm depolarization. Sera from COVID-19 patients in the ICU induced a significant increase in apoptosis markers (ΔΨm depolarization, cytosolic Ca2+, and PS externalization) compared with healthy volunteers and septic ICU controls. Interestingly, immunoglobulin G fractions from COVID-19 patients induced an Fcγ receptor IIA–dependent platelet apoptosis (ΔΨm depolarization, cytosolic Ca2+, and PS externalization). Enhanced PS externalization in platelets from COVID-19 patients in the ICU was associated with increased sequential organ failure assessment score (r= 0.5635) and D-dimer (r= 0.4473). Most importantly, patients with thrombosis had significantly higher PS externalization compared with those without. The strong correlations between markers for apoptosic and procoagulant platelets and D-dimer levels, as well as the incidence of thrombosis, may indicate that antibody-mediated procoagulant platelets potentially contributes to sustained increased thromboembolic risk in ICU COVID-19 patients.
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- 2021
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12. Antibody-induced procoagulant platelets in severe COVID-19 infection
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Althaus, Karina, Marini, Irene, Zlamal, Jan, Pelzl, Lisann, Singh, Anurag, Häberle, Helene, Mehrländer, Martin, Hammer, Stefanie, Schulze, Harald, Bitzer, Michael, Malek, Nisar, Rath, Dominik, Bösmüller, Hans, Nieswandt, Bernard, Gawaz, Meinrad, Bakchoul, Tamam, and Rosenberger, Peter
- Abstract
The pathophysiology of COVID-19–associated thrombosis seems to be multifactorial. We hypothesized that COVID-19 is accompanied by procoagulant platelets with subsequent alteration of the coagulation system. We investigated depolarization of mitochondrial inner transmembrane potential (ΔΨm), cytosolic calcium (Ca2+) concentration, and phosphatidylserine (PS) externalization. Platelets from COVID-19 patients in the intensive care unit (ICU; n = 21) showed higher ΔΨm depolarization, cytosolic Ca2+, and PS externalization compared with healthy controls (n = 18) and non-ICU COVID-19 patients (n = 4). Moreover, significant higher cytosolic Ca2+ and PS were observed compared with a septic ICU control group (ICU control; n = 5). In the ICU control group, cytosolic Ca2+ and PS externalization were comparable with healthy controls, with an increase in ΔΨm depolarization. Sera from COVID-19 patients in the ICU induced a significant increase in apoptosis markers (ΔΨm depolarization, cytosolic Ca2+, and PS externalization) compared with healthy volunteers and septic ICU controls. Interestingly, immunoglobulin G fractions from COVID-19 patients induced an Fcγ receptor IIA–dependent platelet apoptosis (ΔΨm depolarization, cytosolic Ca2+, and PS externalization). Enhanced PS externalization in platelets from COVID-19 patients in the ICU was associated with increased sequential organ failure assessment score (r = 0.5635) and D-dimer (r = 0.4473). Most importantly, patients with thrombosis had significantly higher PS externalization compared with those without. The strong correlations between markers for apoptosic and procoagulant platelets and D-dimer levels, as well as the incidence of thrombosis, may indicate that antibody-mediated procoagulant platelets potentially contributes to sustained increased thromboembolic risk in ICU COVID-19 patients.
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- 2021
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13. Defibrotide for the Treatment of Pediatric Inflammatory Multisystem Syndrome Temporally Associated With Severe Acute Respiratory Syndrome Coronavirus 2 Infection in 2 Pediatric Patients.
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Lang, Peter, Eichholz, Thomas, Bakchoul, Tamam, Streiter, Monika, Petrasch, Maurice, Bösmüller, Hans, Klein, Reinhild, Rabsteyn, Armin, Lang, Anne-Marie, Adams, Constantin, Klingel, Karin, Gessner, Michaela, Rosenberger, Peter, Ruef, Peter, and Handgretinger, Rupert
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The pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 infection is a severe complication of coronavirus disease 2019. Since impaired coagulation and thrombosis/endotheliitis are suspected pathomechanisms, we treated 2 patients with defibrotide, a profibrinolytic, antithrombotic, antiinflammatory oligonucleotide. Symptoms resolved during treatment. Moreover, coagulation parameters indicating hypofibrinolysis and complement activation normalized. The pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 infection is a severe complication of coronavirus disease 2019. Since impaired coagulation and thrombosis/endotheliitis are suspected pathomechanisms, 2 patients received defibrotide, a profibrinolytic, antithrombotic, antiinflammatory oligonucleotide. Symptoms resolved and hypofibrinolysis/complement activation normalized during treatment.
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- 2020
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14. Regional Right Ventricular Volume and Function Analysis Using Intraoperative 3-Dimensional Echocardiography–Derived Mesh Models.
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Nowak-Machen, Martina, Lang, Tobias, Schilling, Andreas, Mockenhaupt, Lisa, Keller, Marius, Rosenberger, Peter, and Magunia, Harry
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In daily echocardiographic practice, the right ventricle (RV) is assessed using mostly 2-dimensional (2D) echocardiography. Parameters measuring longitudinal shortening (eg, tricuspid annular plane systolic excursion) or changes in areas (eg, fractional area change) are used as surrogates for right ventricular function. Three-dimensional (3D) echocardiography–based techniques allow for cardiac magnetic resonance imaging–validated assessment of the RV. Depiction of regional right ventricular function is of increasing clinical interest. This study aimed to calculate regional volumetric changes in the right ventricular inlet, apical section, and outflow tract. Correlations between traditional parameters and regional right ventricular function were studied. Retrospective cohort study on patients scheduled for cardiac surgery. Tertiary care university hospital. The study comprised 80 patients scheduled for cardiac surgery. Based on 3D echocardiographic datasets, mesh models of the RV were generated on a vendor-independent platform. The meshes were further cut into the following 3 regions: the inlet part, the apical section, and the outflow tract. The regional volumes and ejection fractions were compared with the global right ventricular and left ventricular functions. Regional volumes were correlated linearly with the global end-diastolic volume. The right ventricular outflow tract demonstrated a significantly lower ejection fraction than the inlet part (34% ± 11% v 28% ± 11%; p = 0.0054). The function in the right ventricular outflow tract was reduced significantly compared with the global right ventricular function in patients with severely reduced left ventricular ejection fraction (<20%). The different parts of the RV seem to have different ejection fractions. Different regions of the RV are affected differently by reduced left ventricular ejection fraction. Regional right ventricular analyses could help clinicians better understand pathologic states of the RV. [ABSTRACT FROM AUTHOR]
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- 2019
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15. Semaphorin 7A coordinates neutrophil response during pulmonary inflammation and sepsis
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Granja, Tiago, Köhler, David, Tang, Linyan, Burkard, Philipp, Eggstein, Claudia, Hemmen, Katherina, Heinze, Katrin G., Heck-Swain, Ka-Lin, Koeppen, Michael, Günther, Sven, Blaha, Maximilian, Magunia, Harry, Bamberg, Maximilian, Konrad, Franziska, Ngamsri, Kristian-Christos, Fuhr, Anika, Keller, Marius, Bernard, Alice M., Haeberle, Helene A., Bakchoul, Tamam, Zarbock, Alexander, Nieswandt, Bernhard, and Rosenberger, Peter
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•Sema7A controls neutrophil chemotaxis in vitro and the formation of platelet-neutrophil complexes in vivo.•Sema7A influences the early phase of inflammation, which is relevant to the outcome in murine experimental sepsis.
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- 2024
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16. Statistical analysis plan for the Biomarker-guided intervention to prevent acute kidney injury after major surgery (BigpAK-2) study - an international randomised controlled multicenter trial
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von Groote, Thilo, Danzer, Moritz Fabian, Meersch, Melanie, Zarbock, Alexander, Gerß, Joachim, Wempe, Carola, Storck, Michael, Brix, Tobias, Strauss, Christian, Sadjadi, Mahan, Weiss, Raphael, Booke, Hendrik, Loomann, Lisa, Amini, Wida, Meschede, Dana, Göbel, Ulrich, Haaker, Jan Gerrit, Brenner, Thorsten, Espeter, Florian, Rahmel, Tim, Adamzik, Michael, Brandenburger, Timo, Putensen, Christian, Bode, Christian, Kruse, Philippe, Wild, Lennart, Rosenberger, Peter, Bernard, Alice, Jung-König, Mona, Larmann, Jan, Reutershan, Jörg, Arndt, Christian, Vojnar, Benjamin, Spieth, Peter M., Schneider, Antoine, Monard, Céline, Mura, Benedetta, Villa, Gianluca, Laici, Cristiana, Siniscalchi, Antonio, Capozzi, Chiara, Sita, Marco, Cattin, Lucia, de Rosa, Silvia, Spadaro, Savino, Franco, D'Arcangelo Benito, Ostermann, Marlies, Gossage, James, Verzelloni, Alessandra, Scaramuzzi, Marco, Glass, Adam, Silversides, Jon, Lonsdale, Elliot, Forni, Lui G., Haider, Syeda, Rossiter, Adam, Welters, Ingeborg, Hoste, Eric, Hollmann, Markus W., Ripollés-Melchor, Javier, Fernández-Valdes-Bango, Paula, Parise-Roux, Diego, Martin González, Maria Carmen, Bathal, Irene Romero, Jáuregui, Maider Puyada, Navarro-Perez, Rosalía, De Soto, Inés, García-Álvarez, Raquel, Sánchez, Elena Murcia, Suarez-de-la-Rica, Alejandro, and Lalande, Robin
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Acute kidney injury (AKI) is a common and often severe complication after major surgery. Postoperative AKI is associated with a considerable increase in morbidity and mortality. As no specific treatments exist, prevention of AKI is of high importance.
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- 2024
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17. Impact of P-selectin–PSGL-1 Axis on Platelet-Endothelium-Leukocyte Interactions in Fatal COVID-19
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Granai, Massimo, Warm, Verena, Vogelsberg, Antonio, Milla, Jakob, Greif, Karen, Vogel, Ulrich, Bakchoul, Tamam, Rosenberger, Peter, Quintanilla-Martinez, Leticia, Schürch, Christian M., Klingel, Karin, Fend, Falko, and Bösmüller, Hans
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In critically ill patients infected with SARS-CoV-2, early leukocyte recruitment to the respiratory system was found to be orchestrated by leukocyte trafficking molecules accompanied by massive secretion of proinflammatory cytokines and hypercoagulability. Our study aimed to explore the interplay between leukocyte activation and pulmonary endothelium in different disease stages of fatal COVID-19. Our study comprised 10 COVID-19 postmortem lung specimens and 20 control lung samples (5 acute respiratory distress syndrome, 2 viral pneumonia, 3 bacterial pneumonia, and 10 normal), which were stained for antigens representing the different steps of leukocyte migration: E-selectin, P-selectin, PSGL-1, ICAM1, VCAM1, and CD11b. Image analysis software QuPath was used for quantification of positive leukocytes (PSGL-1 and CD11b) and endothelium (E-selectin, P-selectin, ICAM1, VCAM1). Expression of IL-6 and IL-1β was quantified by RT-qPCR. Expression of P-selectin and PSGL-1 was strongly increased in the COVID-19 cohort compared with all control groups (COVID-19:Controls, 17:23, P< .0001; COVID-19:Controls, 2:75, P< .0001, respectively). Importantly, P-selectin was found in endothelial cells and associated with aggregates of activated platelets adherent to the endothelial surface in COVID-19 cases. In addition, PSGL-1 staining disclosed positive perivascular leukocyte cuffs, reflecting capillaritis. Moreover, CD11b showed a strongly increased positivity in COVID-19 compared with all controls (COVID-19:Controls, 2:89; P = .0002), indicating a proinflammatory immune microenvironment. Of note, CD11b exhibited distinct staining patterns at different stages of COVID-19 disease. Only in cases with very short disease course, high levels of IL-1β and IL-6 mRNA were observed in lung tissue. The striking upregulation of PSGL-1 and P-selectin reflects the activation of this receptor–ligand pair in COVID-19, increasing the efficiency of initial leukocyte recruitment, thus promoting tissue damage and immunothrombosis. Our results show that endothelial activation and unbalanced leukocyte migration play a central role in COVID-19 involving the P-selectin–PSGL-1 axis.
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- 2023
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18. Echocardiographic Features of the Fully Magnetically Levitated LVAD.
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Magunia, Harry, Schibilsky, David, Hilberath, Jan N., Schlensak, Christian, Rosenberger, Peter, and Nowak-Machen, Martina
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- 2017
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19. 2D Echocardiographic Evaluation of Right Ventricular Function Correlates With 3D Volumetric Models in Cardiac Surgery Patients.
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Magunia, Harry, Schmid, Eckhard, Hilberath, Jan N., Häberle, Leo, Grasshoff, Christian, Schlensak, Christian, Rosenberger, Peter, and Nowak-Machen, Martina
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Objectives The early diagnosis and treatment of right ventricular (RV) dysfunction are of critical importance in cardiac surgery patients and impact clinical outcome. Two-dimensional (2D) transesophageal echocardiography (TEE) can be used to evaluate RV function using surrogate parameters due to complex RV geometry. The aim of this study was to evaluate whether the commonly used visual evaluation of RV function and size using 2D TEE correlated with the calculated three-dimensional (3D) volumetric models of RV function. Design and Setting Retrospective study, single center, University Hospital. Participants and Intervention Seventy complete datasets were studied consisting of 2D 4-chamber view loops (2-3 beats) and the corresponding 4-chamber view 3D full-volume loop of the right ventricle. RV function and RV size of the 2D loops then were assessed retrospectively purely qualitatively individually by 4 clinician echocardiographers certified in perioperative TEE. Corresponding 3D volumetric models calculating RV ejection fraction and RV end-diastolic volumes then were established and compared with the 2D assessments. Measurements and Main Results 2D assessment of RV function correlated with 3D volumetric calculations (Spearman’s rho –0.5; p<0.0001). No correlation could be established between 2D estimates of RV size and actual 3D volumetric end-diastolic volumes (Spearman’s rho 0.15; p = 0.25). Conclusion The 2D assessment of right ventricular function based on visual estimation as frequently used in clinical practice appeared to be a reliable method of RV functional evaluation. However, 2D assessment of RV size seemed unreliable and should be used with caution. [ABSTRACT FROM AUTHOR]
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- 2017
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20. Resolution of inflammation and sepsis survival are improved by dietary O-3 fatty acids
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Körner, Andreas, Schlegel, Martin, Theurer, Julia, Frohnmeyer, Hannes, Adolph, Michael, Heijink, Marieke, Giera, Martin, Rosenberger, Peter, and Mirakaj, Valbona
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Critical conditions such as sepsis following infection or traumatic injury disturb the complex state of homeostasis that may lead to uncontrolled inflammation resulting in organ failure, shock and death. They are associated with endogenous mediators that control the onset of acute inflammatory response, but the central problem remains the complete resolution of inflammation. Omega-3 enriched lipid emulsions (?-3+LEs) were used in experimental studies and clinical trials to establish homeostasis, yet with little understanding about their role on the resolution of inflammation and tissue regeneration. Here, we demonstrate that ?-3 lipid emulsions (LEs) orchestrate inflammation-resolution/regeneration mechanism during sterile peritonitis and murine polymicrobial sepsis. ?-3+LEs recessed neutrophil infiltration, reduced pro-inflammatory mediators, reduced the classical monocyte and enhanced the non-classical monocytes/macrophages recruitment and finally increased the efferocytosis in sepsis. The actions of ?-3+LE were 5-lipoxygenase (5-LOX) and 12/15-lipoxygenase (12/15-LOX) dependent. ?-3+LEs shortened the resolution interval by 56%, stimulated the endogenous biosynthesis of resolution mediators lipoxin A4, protectin DX and maresin 1 and contributed to tissue regeneration. ?-3+LEs protected against hypothermia and weight loss and enhanced survival in murine polymicrobial sepsis. We highlighted a role of ?-3+LEs in regulating key mechanisms within the resolution terrain during murine sepsis. This might form the basis for a rational design of sepsis specific clinical nutrition.
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- 2018
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21. Whole-body perfusion improves intraoperative transfusions in neonatal aortic arch surgery
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Sandoval Boburg, Rodrigo, Berger, Rafal, Mustafi, Migdat, Faust, Charlotte, Magunia, Harry, Neunhoeffer, Felix, Hofbeck, Michael, Rosenberger, Peter, and Schlensak, Christian
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Aortic arch reconstruction surgery represents a challenge for the whole team involved in the treatment of these complex patients, especially in neonates and infants.
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- 2023
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22. Effects of Mechanical Ventilation on Heart Geometry and Mitral Valve Leaflet Coaptation During Percutaneous Edge-to-Edge Mitral Valve Repair.
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Patzelt, Johannes, Zhang, Yingying, Seizer, Peter, Magunia, Harry, Henning, Andreas, Riemlova, Veronika, Patzelt, Tara A.E., Hansen, Marc, Haap, Michael, Riessen, Reimer, Lausberg, Henning, Walker, Tobias, Reutershan, Joerg, Schlensak, Christian, Grasshoff, Christian, Simon, Dan I., Rosenberger, Peter, Schreieck, Juergen, Gawaz, Meinrad, and Langer, Harald F.
- Abstract
Objectives This study sought to evaluate a ventilation maneuver to facilitate percutaneous edge-to-edge mitral valve repair (PMVR) and its effects on heart geometry. Background In patients with challenging anatomy, the application of PMVR is limited, potentially resulting in insufficient reduction of mitral regurgitation (MR) or clip detachment. Under general anesthesia, however, ventilation maneuvers can be used to facilitate PMVR. Methods A total of 50 consecutive patients undergoing PMVR were included. During mechanical ventilation, different levels of positive end-expiratory pressure (PEEP) were applied, and parameters of heart geometry were assessed using transesophageal echocardiography. Results We found that increased PEEP results in elevated central venous pressure. Specifically, central venous pressure increased from 14.0 ± 6.5 mm Hg (PEEP 3 mm Hg) to 19.3 ± 5.9 mm Hg (PEEP 20 mm Hg; p < 0.001). As a consequence, the reduced pre-load resulted in reduction of the left ventricular end-systolic diameter from 43.8 ± 10.7 mm (PEEP 3 mm Hg) to 39.9 ± 11.0 mm (PEEP 20 mm Hg; p < 0.001), mitral valve annulus anterior-posterior diameter from 32.4 ± 4.3 mm (PEEP 3 mm Hg) to 30.5 ± 4.4 mm (PEEP 20 mm Hg; p < 0.001), and the medio-lateral diameter from 35.4 ± 4.2 mm to 34.1 ± 3.9 mm (p = 0.002). In parallel, we observed a significant increase in leaflet coaptation length from 3.0 ± 0.8 mm (PEEP 3 mm Hg) to 5.4 ± 1.1 mm (PEEP 20 mm Hg; p < 0.001). The increase in coaptation length was more pronounced in MR with functional or mixed genesis. Importantly, a coaptation length >4.9 mm at PEEP of 10 mm Hg resulted in a significant reduction of PMVR procedure time (152 ± 49 min to 116 ± 26 min; p = 0.05). Conclusions In this study, we describe a novel ventilation maneuver improving mitral valve coaptation length during the PMVR procedure, which facilitates clip positioning. Our observations could help to improve PMVR therapy and could make nonsurgical candidates accessible to PMVR therapy, particularly in challenging cases with functional MR. [ABSTRACT FROM AUTHOR]
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- 2016
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23. Echocardiography for Less-Invasive Implantation of Left Ventricular Assist Devices
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Magunia, Harry, Schlensak, Christian, Schibilsky, David, Hilberath, Jan N., Rosenberger, Peter, and Nowak-Machen, Martina
- Abstract
Supplemental Digital Content is available in the text.New surgical techniques aim for less-invasive implantation of left ventricular assist devices (LVADs) viasmall surgical incision sites. Echocardiography plays an important role during patient selection and guidance of the procedure. The surgical incision site can be identified preoperatively by transthoracic echocardiography. Intraoperative identification of left ventricular apex, de-airing, and monitoring heart function is performed by transesophageal echocardiography. This article highlights special echocardiographic considerations during less-invasive LVAD implantation surgeries.
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- 2017
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24. Systolic heart failure: diagnosis and therapy
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Henes, Janek and Rosenberger, Peter
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- 2016
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25. Hypoxia-Inducible Factor–Dependent Repression of Equilibrative Nucleoside Transporter 2 Attenuates Mucosal Inflammation During Intestinal Hypoxia.
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Morote–Garcia, Julio C., Rosenberger, Peter, Nivillac, Nicole M.I., Coe, Imogen R., and Eltzschig, Holger K.
- Subjects
TRANSCRIPTION factors ,HYPOXEMIA ,INTESTINAL mucosa ,NUCLEOSIDES ,ADENOSINES ,SMALL interfering RNA ,INFLAMMATION ,CELL receptors - Abstract
Background & Aims: The surface of the intestinal mucosa is particularly prone to hypoxia-induced inflammation. Previous studies implicated signaling via extracellular adenosine in endogenous attenuation of intestinal inflammation; we investigated whether epithelial adenosine transport could reduce hypoxia-induced inflammation of the mucosa. Methods: We performed in vitro studies of epithelial adenosine uptake and nucleoside transport using cultured epithelial cells. In vivo studies of ambient hypoxia levels were performed using mice with conditional loss of hypoxia-inducible factor (HIF)-α expression in the colon. Results: Studies of epithelial adenosine transport under hypoxic conditions showed that extracellular adenosine uptake occurs mainly at the apical surface of epithelial cells and is attenuated by hypoxia. Subsequent transcriptional studies suggested high expression levels of the equilibrative nucleoside transporter-2 (ENT2) in human epithelial cells and revealed ENT2 repression during hypoxia. Studies with promoter constructs, including site-directed mutagenesis, transcription factor binding assays, and HIF loss and gain of function showed a central role of HIF-1α in transcriptional repression of ENT2 during hypoxia. Similarly, transcriptional repression of ENT2 by ambient hypoxia was abolished in conditional HIF-1α mutant mice in vivo. Functional studies using RNA interference showed that loss of epithelial ENT2 was associated with reduced adenosine uptake in vitro, whereas pharmacologic inhibition of ENT2 attenuated hypoxia-induced inflammation of the mucosa in vivo. Conclusions: HIF-1α–dependent repression of ENT2 increases mucosal adenosine signaling and attenuates hypoxia-associated inflammation of the intestine. [Copyright &y& Elsevier]
- Published
- 2009
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26. Impact of Intraoperative Transesophageal Echocardiography on Surgical Decisions in 12,566 Patients Undergoing Cardiac Surgery.
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Eltzschig, Holger K., Rosenberger, Peter, Löffler, Michaela, Fox, John A., Aranki, Sary F., and Shernan, Stanton K.
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CARDIAC surgery patients ,ECHOCARDIOGRAPHY ,CARDIOGRAPHY ,PATIENTS - Abstract
Background: The utility of intraoperative transesophageal echocardiography (TEE) for different types of cardiac surgical procedures has not been thoroughly investigated despite its increasing popularity. Therefore, we retrospectively evaluated the impact of before and after cardiopulmonary bypass (CPB) TEE on surgical decisions in 12,566 consecutive patients undergoing cardiac surgery at a single institution. Methods: We analyzed all patients undergoing cardiac surgical procedures who had an intraoperative TEE examination between 1990 and 2005 at the Brigham and Women’s Hospital. Results of the TEE examinations were entered into a database. Previously undiagnosed TEE findings from the pre- and post-CPB examinations that directly impacted surgical decisions were evaluated. Results: Before and after CPB TEE examinations influenced surgical decision making in 7.0% and 2.2%, respectively, of all evaluated patients (n = 12,566). In patients undergoing only coronary artery bypass graft surgery (CABG [n = 3,835]), surgical decisions were influenced by 5.4% of the pre-CPB and 1.5% of the post-CPB TEE examinations, and in 6.3% and 3.3%, respectively, of those patients undergoing isolated valve procedures (n = 3,840). In combined CABG and valve procedures (n = 2,944), surgical decisions were influenced by 12.3% of the pre-CPB and 2.2% of the post-CPB TEE examinations. Conclusions: Intraoperative TEE influences cardiac surgical decisions in more than 9% of all patients in the presented study population, with the greatest observed impact in patients undergoing combined CABG and valve procedures. [Copyright &y& Elsevier]
- Published
- 2008
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27. The Influence of Epiaortic Ultrasonography on Intraoperative Surgical Management in 6051 Cardiac Surgical Patients.
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Rosenberger, Peter, Shernan, Stanton K., Löffler, Michaela, Shekar, Prem S., Fox, John A., Tuli, Jayshree K., Nowak, Martina, and Eltzschig, Holger K.
- Subjects
PATIENTS ,DECISION making ,CATHETERIZATION complications ,MEDICAL care - Abstract
Background: Intraoperative echocardiography has become a mainstay monitor of cardiac function and a popular diagnostic tool in patients undergoing cardiac procedures. Previous reports suggest that epiaortic ultrasonography (EU) is superior to transesophageal echocardiography and manual palpation in identifying ascending aortic atheroma. Its impact on surgical decision making has not been thoroughly investigated, however. Methods: We retrospectively analyzed the medical records of 6051 consecutive patients who underwent EU of their ascending aorta during cardiac operations between 1996 and 2006 to determine a potential impact on intraoperative surgical decision making. Aortic atheroma was graded according to standard classification. Neurologic complications were evaluated according to the Society of Thoracic Surgeon definition for stroke and transient ischemic attack (TIA). Results: The overall impact of EU on surgical decision making was 4.1% and included a change in the technique for inducing cardiac arrest in 1.8%, aortic atherectomy or replacement surgery in 0.8%, requirement for off-pump coronary artery bypass grafting (CABG) in 0.6%, avoidance of aortic cross-clamping and use of ventricular fibrillatory arrest in 0.5%, change in arterial cannulation site in 0.2%, or avoidance of aortic cannulation in 0.2%. The greatest affect of EU was observed in patients undergoing combined CABG with aortic/mitral valve procedures (6.7%). The smallest impact was seen in patients undergoing mitral valve operations (1.4%). Aortic atheroma was more frequent on the anterior aspect of the aorta (n = 171) in patients with a change in surgical plan than on the posterior aspect (n = 78). The overall stroke rate was lower in patients with intraoperative EU compared with all patients undergoing surgical procedures. Conclusions: Epiaortic ultrasonography is a useful technique to detect ascending aortic atheroma, has a significant impact on surgical decision making in more than 4% of cardiac surgical patients, and might result in improved perioperative neurologic outcome. [Copyright &y& Elsevier]
- Published
- 2008
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28. Transesophageal echocardiography for detecting extrapulmonary thrombi during pulmonary embolectomy.
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Rosenberger, Peter, Shernan, Stanton K., Mihaljevic, Tomislav, and Eltzschig, Holger K.
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EMBOLISMS ,ARTERIAL occlusions ,TRANSESOPHAGEAL echocardiography ,RIGHT heart ventricle ,THROMBOEMBOLISM - Abstract
Background: Pulmonary embolectomy is an evolving surgical procedure for the treatment of severe pulmonary embolism. In addition to removing pulmonary thromboemboli, the achievement of optimal results also requires identification and extraction of intrathoracic, extrapulmonary thromboemboli from the right atrium, right ventricle, and the superior or inferior vena cava. Otherwise, these thromboemboli may become the source of recurrent pulmonary embolism. Intraoperative transesophageal echocardiography is frequently used during pulmonary embolectomy as a guide for the surgeon and a monitor of cardiac performance. However, its utility for detecting concurrent intrathoracic, extrapulmonary thromboemboli has not been thoroughly investigated.Methods: The study population included 50 consecutive patients undergoing emergent pulmonary embolectomy. Results from preoperative diagnostic studies including transthoracic echocardiography; ventilation/perfusion scan, pulmonary angiography, and computed tomography were reviewed, along with the intraoperative echocardiographic reports for the presence of intrathoracic extrapulmonary thromboemboli. In addition, the surgical operative notes were consulted to determine the impact of intraoperative transesophageal echocardiography on surgical decision making.Results: Extrapulmonary intrathoracic thromboemboli were identified preoperatively in 8 patients (16%). Intraoperatively, thromboemboli were identified in 5 additional patients by transesophageal echocardiography, adding to a total of 13 patients with extrapulmonary thrombi (26%). Intraoperative transesophageal echocardiography provided the sole source of evidence that directed surgical management in 10% (5 of 50) of all patients undergoing pulmonary emboletcomy.Conclusions: Intraoperative transesophageal echocardiography identified intrathoracic, extrapulmonary thomboemboli in 26% of patients undergoing pulmonary embolectomy, resulting in an alteration of surgical management in 10% of patients. These findings support the critical role of intraoperative echocardiography during pulmonary embolectomy. [Copyright &y& Elsevier]
- Published
- 2004
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29. Vagus nerve controls resolution and pro-resolving mediators of inflammation
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Mirakaj, Valbona, Dalli, Jesmond, Granja, Tiago, Rosenberger, Peter, and Serhan, Charles N.
- Abstract
Resolution of inflammation is now recognized as a biosynthetically active process involving pro-resolving mediators. Here, we show in zymosan-initiated peritoneal inflammation that the vagus nerve regulates local expression of netrin-1, an axonal guidance molecule that activates resolution, and that vagotomy reduced local pro-resolving mediators, thereby delaying resolution. In netrin-1+/− mice, resolvin D1 (RvD1) was less effective in reducing neutrophil influx promoting resolution of peritonitis compared with Ntn1+/+. Netrin-1 shortened the resolution interval, decreasing exudate neutrophils, reducing proinflammatory mediators, and stimulating the production of resolvins, protectins, and lipoxins. Human monocytes incubated with netrin-1 produced proresolving mediators, including resolvins and lipoxins. Netrin-1 and RvD1 displayed bidirectional activation in that they stimulated each other’s expression and enhanced efferocytosis. These results indicate that the vagus nerve regulates both netrin-1 and pro-resolving lipid mediators, which act in a bidirectional fashion to stimulate resolution, and provide evidence for a novel mechanism for local neuronal control of resolution.
- Published
- 2014
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30. Selective induction of endothelial P2Y6 nucleotide receptor promotes vascular inflammation
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Riegel, Ann-Kathrin, Faigle, Marion, Zug, Stephanie, Rosenberger, Peter, Robaye, Bernard, Boeynaems, Jean-Marie, Idzko, Marco, and Eltzschig, Holger K.
- Abstract
During a systemic inflammatory response endothelial-expressed surface molecules have been strongly implicated in orchestrating immune responses. Previous studies have shown enhanced extracellular nucleotide release during acute inflammatory conditions. Therefore, we hypothesized that endothelial nucleotide receptors could play a role in vascular inflammation. To address this hypothesis, we performed screening experiments and exposed human microvascular endothelia to inflammatory stimuli, followed by measurements of P2Y or P2X transcriptional responses. These studies showed a selective induction of the P2Y6 receptor (> 4-fold at 24 hours). Moreover, studies that used real-time reverse transcription–polymerase chain reaction, Western blot analysis, or immunofluorescence confirmed time- and dose-dependent induction of P2Y6 with tumor necrosis factor α or Lipopolysaccharide (LPS) stimulation in vitro and in vivo. Studies that used MRS 2578 as P2Y6 receptor antagonist showed attenuated nuclear factor κB reporter activity and proinflammatory gene expression in human microvascular endothelial cells in vitro. Moreover, pharmacologic or genetic in vivo studies showed attenuated inflammatory responses in P2Y6−/− mice or after P2Y6 antagonist treatment during LPS-induced vascular inflammation. These studies show an important contribution of P2Y6 signaling in enhancing vascular inflammation during systemic LPS challenge and implicate the P2Y6 receptor as a therapeutic target during systemic inflammatory responses.
- Published
- 2011
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31. Selective induction of endothelial P2Y6nucleotide receptor promotes vascular inflammation
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Riegel, Ann-Kathrin, Faigle, Marion, Zug, Stephanie, Rosenberger, Peter, Robaye, Bernard, Boeynaems, Jean-Marie, Idzko, Marco, and Eltzschig, Holger K.
- Abstract
During a systemic inflammatory response endothelial-expressed surface molecules have been strongly implicated in orchestrating immune responses. Previous studies have shown enhanced extracellular nucleotide release during acute inflammatory conditions. Therefore, we hypothesized that endothelial nucleotide receptors could play a role in vascular inflammation. To address this hypothesis, we performed screening experiments and exposed human microvascular endothelia to inflammatory stimuli, followed by measurements of P2Y or P2X transcriptional responses. These studies showed a selective induction of the P2Y6receptor (> 4-fold at 24 hours). Moreover, studies that used real-time reverse transcription–polymerase chain reaction, Western blot analysis, or immunofluorescence confirmed time- and dose-dependent induction of P2Y6with tumor necrosis factor α or Lipopolysaccharide (LPS) stimulation in vitro and in vivo. Studies that used MRS 2578 as P2Y6receptor antagonist showed attenuated nuclear factor κB reporter activity and proinflammatory gene expression in human microvascular endothelial cells in vitro. Moreover, pharmacologic or genetic in vivo studies showed attenuated inflammatory responses in P2Y6−/−mice or after P2Y6antagonist treatment during LPS-induced vascular inflammation. These studies show an important contribution of P2Y6signaling in enhancing vascular inflammation during systemic LPS challenge and implicate the P2Y6receptor as a therapeutic target during systemic inflammatory responses.
- Published
- 2011
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32. HIF-1–dependent repression of adenosine kinase attenuates hypoxia-induced vascular leak
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Morote-Garcia, Julio C., Rosenberger, Peter, Kuhlicke, Johannes, and Eltzschig, Holger K.
- Abstract
Extracellular adenosine has been implicated in vascular adaptation to hypoxia. Based on the observation that increases in intracellular adenosine can effectively elevate extracellular adenosine, we studied the contribution of adenosine kinase (AK, intracellular conversion of adenosine to adenosine monophosphate [AMP]) to vascular adenosine responses. Initial in vitro studies of ambient hypoxia revealed prominent repression of endothelial AK transcript (85% ± 2% reduction), protein, and function. Transcription factor binding assays and hypoxia inducible factor 1-α (HIF-1α) loss- and gain-of-function studies suggested a role for HIF-1α in transcriptional repression of AK. Moreover, repression of AK by ambient hypoxia was abolished in conditional HIF-1α mutant mice in vivo. Studies of endothelial barrier function revealed that inhibition or siRNA repression of AK is associated with enhanced adenosine-dependent barrier responses in vitro. Moreover, in vivo studies of vascular barrier function demonstrated that AK inhibition with 5′-iodotubericidin (1 mg/kg prior to hypoxia) significantly attenuated hypoxia-induced vascular leakage in multiple organs and reduced hypoxia-associated increases in lung water. Taken together, our data reveal a critical role of AK in modulating vascular adenosine responses and suggest pharmacologic inhibitors of AK in the treatment of conditions associated with hypoxia-induced vascular leakage (eg, sepsis or acute lung injury).
- Published
- 2008
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33. HIF-1–dependent repression of adenosine kinase attenuates hypoxia-induced vascular leak
- Author
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Morote-Garcia, Julio C., Rosenberger, Peter, Kuhlicke, Johannes, and Eltzschig, Holger K.
- Abstract
Extracellular adenosine has been implicated in vascular adaptation to hypoxia. Based on the observation that increases in intracellular adenosine can effectively elevate extracellular adenosine, we studied the contribution of adenosine kinase (AK, intracellular conversion of adenosine to adenosine monophosphate [AMP]) to vascular adenosine responses. Initial in vitro studies of ambient hypoxia revealed prominent repression of endothelial AK transcript (85% ± 2% reduction), protein, and function. Transcription factor binding assays and hypoxia inducible factor 1-α (HIF-1α) loss- and gain-of-function studies suggested a role for HIF-1α in transcriptional repression of AK. Moreover, repression of AK by ambient hypoxia was abolished in conditional HIF-1α mutant mice in vivo. Studies of endothelial barrier function revealed that inhibition or siRNA repression of AK is associated with enhanced adenosine-dependent barrier responses in vitro. Moreover, in vivo studies of vascular barrier function demonstrated that AK inhibition with 5′-iodotubericidin (1 mg/kg prior to hypoxia) significantly attenuated hypoxia-induced vascular leakage in multiple organs and reduced hypoxia-associated increases in lung water. Taken together, our data reveal a critical role of AK in modulating vascular adenosine responses and suggest pharmacologic inhibitors of AK in the treatment of conditions associated with hypoxia-induced vascular leakage (eg, sepsis or acute lung injury).
- Published
- 2008
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34. Endothelial catabolism of extracellular adenosine during hypoxia: the role of surface adenosine deaminase and CD26
- Author
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Eltzschig, Holger K., Faigle, Marion, Knapp, Simone, Karhausen, Jorn, Ibla, Juan, Rosenberger, Peter, Odegard, Kirsten C., Laussen, Peter C., Thompson, Linda F., and Colgan, Sean P.
- Abstract
Extracellular levels of adenosine increase during hypoxia. While acute increases in adenosine are important to counterbalance excessive inflammation or vascular leakage, chronically elevated adenosine levels may be toxic. Thus, we reasoned that clearance mechanisms might exist to offset deleterious influences of chronically elevated adenosine. Guided by microarray results revealing induction of endothelial adenosine deaminase (ADA) mRNA in hypoxia, we used in vitro and in vivo models of adenosine signaling, confirming induction of ADA protein and activity. Further studies in human endothelia revealed that ADA-complexing protein CD26 is coordinately induced by hypoxia, effectively localizing ADA activity at the endothelial cell surface. Moreover, ADA surface binding was effectively blocked with glycoprotein 120 (gp120) treatment, a protein known to specifically compete for ADA-CD26 binding. Functional studies of murine hypoxia revealed inhibition of ADA with deoxycoformycin (dCF) enhances protective responses mediated by adenosine (vascular leak and neutrophil accumulation). Analysis of plasma ADA activity in pediatric patients with chronic hypoxia undergoing cardiac surgery demonstrated a 4.1 ± 0.6-fold increase in plasma ADA activity compared with controls. Taken together, these results reveal induction of ADA as innate metabolic adaptation to chronically elevated adenosine levels during hypoxia. In contrast, during acute hypoxia associated with vascular leakage and excessive inflammation, ADA inhibition may serve as therapeutic strategy.
- Published
- 2006
- Full Text
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35. Endothelial catabolism of extracellular adenosine during hypoxia: the role of surface adenosine deaminase and CD26
- Author
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Eltzschig, Holger K., Faigle, Marion, Knapp, Simone, Karhausen, Jorn, Ibla, Juan, Rosenberger, Peter, Odegard, Kirsten C., Laussen, Peter C., Thompson, Linda F., and Colgan, Sean P.
- Abstract
Extracellular levels of adenosine increase during hypoxia. While acute increases in adenosine are important to counterbalance excessive inflammation or vascular leakage, chronically elevated adenosine levels may be toxic. Thus, we reasoned that clearance mechanisms might exist to offset deleterious influences of chronically elevated adenosine. Guided by microarray results revealing induction of endothelial adenosine deaminase (ADA) mRNA in hypoxia, we used in vitro and in vivo models of adenosine signaling, confirming induction of ADA protein and activity. Further studies in human endothelia revealed that ADA-complexing protein CD26 is coordinately induced by hypoxia, effectively localizing ADA activity at the endothelial cell surface. Moreover, ADA surface binding was effectively blocked with glycoprotein 120 (gp120) treatment, a protein known to specifically compete for ADA-CD26 binding. Functional studies of murine hypoxia revealed inhibition of ADA with deoxycoformycin (dCF) enhances protective responses mediated by adenosine (vascular leak and neutrophil accumulation). Analysis of plasma ADA activity in pediatric patients with chronic hypoxia undergoing cardiac surgery demonstrated a 4.1 ± 0.6-fold increase in plasma ADA activity compared with controls. Taken together, these results reveal induction of ADA as innate metabolic adaptation to chronically elevated adenosine levels during hypoxia. In contrast, during acute hypoxia associated with vascular leakage and excessive inflammation, ADA inhibition may serve as therapeutic strategy.
- Published
- 2006
- Full Text
- View/download PDF
36. Decreased Proopiomelanocortin mRNA in Lymphocytes of Chronic Alcoholics After Intravenous Human Corticotropin Releasing Factor Injection
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Rosenberger, Peter, Mühlbauer, Eckhard, Weissmüller, Thomas, Rommelspacher, Hans, Sinha, Pranav, Wernecke, Klaus D., Finckh, Ulrich, Rettig, Jordan, Kox, Wolfgang J., and Spies, Claudia D.
- Abstract
Background: Alcohol abuse may involve an altered neuroendocrine response that mediates lymphocyte‐derived proopiomelanocortin (POMC) production and inflammation. We investigated POMC messenger RNA (mRNA) expression in human lymphocytes ex vivo and their relation to plasma ACTH and immunoreactive β‐endorphin (IR‐β‐EP) after intravenous injection of human corticotropin releasing factor (hCRF) in chronic alcoholics (n= 12) and nonalcoholics (n= 12) before surgery. Lipopolysaccharide‐stimulated interleukin (IL)‐1 receptor antagonist (IL‐1 Ra) as a marker for chronic inflammation was determined.
- Published
- 2003
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37. LABORATORY DIAGNOSIS
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Rosenberger, Peter B. and Timmel, Gretchen
- Abstract
From the physician's perspective, the laboratory diagnosis of learning disabilities is essentially corroborative of history and physical examination. However, since many psychologists and educators tend to think of these disorders in terms of test scores, it is especially important for the physician to understand the common test instruments. The distinctions between aptitude and achievement, between general and specific aptitudes, and between age equivalents and grade equivalents are among those essential to proper interpretation of test scores. An understanding of what physiologically oriented laboratory tests do and do not contribute to diagnosis will help the physician adopt sensible criteria for ordering these tests.
- Published
- 2002
38. MANAGEMENT OF LEARNING DISABILITIES
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Rosenberger, Peter B. and Timmel, Gretchen
- Abstract
Management of a case of learning disability is nearly always the task of a team of which the physician is but one member. Because consultation to the physician is often of the nature of “second opinion,” diplomacy is critical. It is helpful for all to understand that the biological perspective is only 1 of several. The physician has a role not only in evaluation, but also in follow-up over the long term. An especially important distinction is that between remedial instruction and curriculum support.
- Published
- 2002
39. INTRODUCTION
- Author
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Rosenberger, Peter B.
- Abstract
Neurologists are called upon with increasing frequency to provide advice to children and adults who are having difficulty coping with academic challenges. An understanding of specific handicaps to academic function (learning disabilities) is essential to this task. The nature of learning and learning ability (intelligence) must first be grasped, especially the distinction between aptitude and skill. Specific learning disabilities must then be understood as restricted deficits in aptitude for learning.
- Published
- 2002
40. Intelligence and physical features of children of women with epilepsy
- Author
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Holmes, Lewis B., Rosenberger, Peter B., Harvey, Elizabeth A., Khoshbin, Shahram, and Ryan, Louise
- Abstract
The teratogenicity of maternal epilepsy has been attributed to several factors, including the antiepileptic drugs taken to prevent seizures during pregnancy, the occurrence of seizures during pregnancy, and the factors in the mother that caused her to have epilepsy. We have addressed the hypothesis that the children of women who have a history of epilepsy (seizure history), but who took no antiepileptic drugs (AED) and had no tonic-clonic seizures in pregnancy, have an increased risk of malformations and diminished intelligence. The frequency of cognitive dysfunction was determined in 57 seizure history and 57 matched control children aged 6l6 years. The masked evaluation of the children included a physical and neurologic examination and testing with the Wechsler Intelligence Scale for Children-Revised (WISC-R) and a systematic physical examination for the features of the fetal AED syndrome. The evaluation of both parents of each child included a test of reasoning (Ravens Progressive Matrix) and a physical examination. There were no differences between the two groups of children in either IQ scores or physical features; none of the seizure history children was judged to have the anticonvulsant face or digit hypoplasia. This study had 80% power to rule out a difference of seven or more IQ points between the two groups, based on a two-sided test at a 5% level of significance. Our confidence in concluding that there was no difference between seizure history and control infants was strengthened by the fact that no statistically significant differences were observed with respect to multiple outcomes, including eight related measures of intelligence. Thirty (53%) of the seizure history mothers resumed taking AED after the birth of the child we evaluated. Additional studies are needed to address the teratogenicity of the antiepileptic drugs as monotherapy. Teratology 61:196202, 2000. © 2000 Wiley-Liss, Inc.
- Published
- 2000
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41. Autism and unfavorable left-right asymmetries of the brain
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Hier, Daniel, LeMay, Marjorie, and Rosenberger, Peter
- Abstract
Utilizing computerized brain tomography, left-right morphologic asymmetries of the parietooccipital region were judged in 16 autistic patients, 44 mentally retarded patients, and 100 miscellaneous neurological patients. In 57% of the autistic patients the right parietooccipital region was wider than the left, while this pattern of cerebral asymmetry was found in only 23% of the mentally retarded patients and 25% of the neurological patients. It is suggested that unfavorable morphologic asymmetries of the brain near the posterior language zone may contribute to the difficulties autistic children experience in acquiring language.
- Published
- 1979
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42. Discriminative aspects of visual hemiinattention
- Author
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ROSENBERGER, PETER B.
- Abstract
Deficits in visual discrimination were examined in 30 combat soldiers with head wounds, 20 of whom had unilateral lesions (10 right and 10 left) of the posterior cerebral hemispheres and 10 of whom had frontal lobe wounds, left, right or bilateral. Seven of the patients with posterior lesions, but none with frontal lesions, showed visual spatial disorientation as demonstrated by a shift in the peak of the stimulus generalization gradient of an experimentally conditioned sensory discrimination. The peak shift occurred to the side opposite the cerebral lesion in all cases, and the deficit did not occur when the task was presented as a match to sample.
- Published
- 1974
43. Acute Confusion and Mutism as a Presentation of Thalamic Strokes Secondary to Deep Cerebral Venous Thrombosis
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Kothare, Sanjeev V., Ebb, David H., Rosenberger, Peter B., Buonanno, Ferdinando, Schaefer, Pamela W., and Krishnamoorthy, Kalpathy S.
- Published
- 1998
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44. Visual Matching and Clinical Findings Among Good and Poor Readers
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Rosenberger, Peter B.
- Abstract
Certain clinical tests of widely reputed importance to reading disability have been applied, together with semi-automated visual sample-matching tasks, to a randomly selected school population of good and poor readers. Those performance deficits found with significant frequency among the poor readers of normal intelligence include laterality awareness of body parts (although not laterality preference), and visual sample-matching with three-letter words where the match involved only the order of letters within the word. Coincidence of these two findings suggests that further study might elucidate some more general deficit of laterality awareness in significant portions of the total population of normally intelligent poor readers.
- Published
- 1970
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45. Inter- and Intramodality Matching Deficits in a Dysphasic Youth
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Rosenberger, Peter B., Mohr, Jay P., Stoddard, Lawrence T., and Sidman, Murray
- Abstract
THE SUBJECT of this report suffered a stroke at the age of 14, and the available evidence suggests extensive damage to the left (dominant) cerebral hemisphere. During the two years since onset of his illness we have carried out a series of behavioral studies relevant to the general problem of interhemispheric relations, with particular reference to language function.Clinical tests indicated that the patient was unable to write single letters to dictation, or even to select a dictated letter from several available visual choices. He was, however, able to deal fairly effectively with simple words on these tasks. It was this apparent discrepancy which prompted us to seek through special testing techniques a more precise delineation of his behavioral deficits.An additional, although not secondary, purpose of this report is to describe an investigative methodology. As is so often the case, our patient's almost complete lack of oral speech
- Published
- 1968
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46. Habituation and Urinary Retention
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Jammes, Juan L., Tigchelaar, Peter V., and Rosenberger, Peter B.
- Abstract
Four subjects with partial or episodic complete urinary retention and bladder hypotonicity with large urinary residuals underwent "habituation" treatment. Results indicated an exponential decrease in urinary residuals to 0 ml and disappearance of partial or complete urinary retention within 20 weeks. This study is presented as an example of how conditioning therapy may be applied to the treatment of certain neurological disorders.(JAMA 232:1264-1266, 1975)
- Published
- 1975
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47. Developmental Dyslexia: Evidence for a Subgroup With a Reversal of Cerebral Asymmetry
- Author
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Hier, Daniel B., LeMay, Marjorie, Rosenberger, Peter B., and Perlo, Vincent P.
- Abstract
• The computerized brain tomograms of 24 patients with developmental dyslexia were analyzed for cerebral asymmetry. Ten patients showed a reversal of the pattern of asymmetry regularly observed in normal right-handed individuals so that the right parietooccipital region was wider than the left. The ten dyslexic patients with this reversal of cerebral asymmetry had a lower mean verbal IQ than the other 14 dyslexic patients in this study. The reversal of cerebral asymmetry that occurred in ten of the dyslexic patients may result in language lateralization to a cerebral hemisphere that is structurally less suited to support language function and thus act as a risk factor for the development of reading disability.
- Published
- 1978
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48. Big brain/smart brain.
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Rosenberger, Peter B. and Adams, Heather R.
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- 2011
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49. Literature Review.
- Author
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Collard, C. David, Rosenberger, Peter, and Eltzschig, Holger K.
- Published
- 2005
- Full Text
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50. Transesophageal Echocardiography for Pulmonary Embolectomy.
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Rosenberger, Peter, Shernan, Stanton K., Mihaljevic, Tomislav, and Eltzschig, Holger K.
- Published
- 2005
- Full Text
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