46 results on '"Nöldge-Schomburg, Gabriele"'
Search Results
2. Rocuronium is more hepatotoxic than succinylcholine in vitro
- Author
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Sauer, Martin, Piel, Ines, Haubner, Cristof, Richter, Georg, Mann, Miriam, Nöldge-Schomburg, Gabriele, and Mencke, Thomas
- Published
- 2017
- Full Text
- View/download PDF
3. Procalcitonin Impairs Endothelial Cell Function and Viability
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Wagner, Nana-Maria, Van Aken, Caroline, Butschkau, Antje, Bierhansl, Laura, Kellner, Patrick, Schleusener, Viola, Seggewiss, Jochen, Vollmar, Brigitte, Nöldge-Schomburg, Gabriele, and Roesner, Jan Patrick
- Published
- 2017
- Full Text
- View/download PDF
4. Rosiglitazone Dampens Pulmonary Inflammation in a Porcine Model of Acute Lung Injury
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Mirakaj, Valbona, Mutz, Christian, Vagts, Dierk, Henes, Janek, Haeberle, Helene A., Husung, Susanne, König, Tony, Nöldge-Schomburg, Gabriele, and Rosenberger, Peter
- Published
- 2014
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- View/download PDF
5. Laryngeal injuries following endotracheal intubation in ENT surgery: predictive value of anatomical scores
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Böttcher, Arne, Mencke, Thomas, Zitzmann, Amelie, Knecht, Rainald, Jowett, Nathan, Nöldge-Schomburg, Gabriele, Pau, Hans Wilhelm, and Dommerich, Steffen
- Published
- 2014
- Full Text
- View/download PDF
6. A double blind, single centre, sub-chronic reperfusion trial evaluating FX06 following haemorrhagic shock in pigs
- Author
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Roesner, Jan P., Petzelbauer, Peter, Koch, Alexander, Tran, Nguyen, Iber, Thomas, Mutz, Christian, Vollmar, Brigitte, Nöldge-Schomburg, Gabriele E.F., and Zacharowski, Kai
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- 2009
- Full Text
- View/download PDF
7. Accurate and continuous measurement of oxygen deficit during haemorrhage in pigs
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Roesner, Jan P., Koch, Alexander, Bateman, Richard, Scheeren, Thomas W.L., Zander, Rolf, Nöldge-Schomburg, Gabriele E.F., and Zacharowski, Kai
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- 2009
- Full Text
- View/download PDF
8. Impaired cell functions of hepatocytes incubated with plasma of septic patients
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Sauer, Martin, Haubner, Cristof, Mencke, Thomas, Nöldge-Schomburg, Gabriele, Mitzner, Steffen, Altrichter, Jens, and Stange, Jan
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- 2012
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- View/download PDF
9. Comparison of heart rate variability response in children undergoing elective endotracheal intubation with and without neuromuscular blockade: a randomized controlled trial
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Janda, Matthias, Bajorat, Jörn, Kudlik, Christiana, Pohl, Birgit, Schubert, Agnes, Nöldge-Schomburg, Gabriele, Hofmockel, Rainer, and Cote, Charles
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- 2013
- Full Text
- View/download PDF
10. Management of pulmonary aspiration
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Janda, Matthias, Scheeren, Thomas W.L., and Nöldge-Schomburg, Gabriele F.E.
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- 2006
- Full Text
- View/download PDF
11. In-Hospital Outcome of Patients with Severe Mitral Valve Regurgitation Classified as Inoperable and Treated with the MitraClip® Device
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DIVCHEV, DIMITAR, KISCHE, STEPHAN, PARANSKAYA, LILIYA, SCHNEIDER, HENRIK, REHDERS, TIM, ORTAK, JASMIN, AKIN, IBRAHIM, TURAN, GÖKMEN, TURAN, CEM HAKAN, STEINHOFF, GUSTAV, NÖLDGE-SCHOMBURG, GABRIELE, NIENABER, CHRISTOPH A., and INCE, HÜSEYIN
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- 2012
- Full Text
- View/download PDF
12. Correction: The prognostic value of neurofilament levels in patients with sepsis-associated encephalopathy - A prospective, pilot observational study (PLoS One (2019) 14:1 (e0211184) DOI: 10.1371/journal.pone.0211184)
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Ehler, Johannes, Petzold, Axel, Wittstock, Matthias, Kolbaske, Stephan, Gloger, Martin, Henschel, J. rg, Heslegrave, Amanda, Zetterberg, Henrik, Lunn, Michael P., Rommer, Paulus S., Grossmann, Annette, Sharshar, Tarek, Richter, Georg, Nöldge-Schomburg, Gabriele, Sauer, Martin, APH - Methodology, and APH - Mental Health
- Abstract
In Fig 3, the headings above the graph are incorrectly swapped. The left heading should be “No Brain Dysfunction” and the right heading should be “Brain Dysfunction.” The authors have provided a corrected version here. (Figure Presented).
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- 2019
13. The prognostic value of neurofilament levels in patients with sepsis-associated encephalopathy – A prospective, pilot observational study
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Ehler, Johannes, Petzold, Axel, Wittstock, Matthias, Kolbaske, Stephan, Gloger, Martin, Henschel, Jörg, Heslegrave, Amanda, Zetterberg, Henrik, Lunn, Michael P., Rommer, Paulus S., Grossmann, Annette, Sharshar, Tarek, Richter, Georg, Nöldge-Schomburg, Gabriele, Sauer, Martin, APH - Methodology, and APH - Mental Health
- Subjects
Male ,Physiology ,Intermediate Filaments ,Social Sciences ,Pilot Projects ,Pathology and Laboratory Medicine ,Severity of Illness Index ,Nervous System ,Diagnostic Radiology ,Medicine and Health Sciences ,Psychology ,Prospective Studies ,Brain Damage ,Cerebrospinal Fluid ,Aged, 80 and over ,Clinical Neurophysiology ,Brain Diseases ,Brain Mapping ,Cognitive Neurology ,Radiology and Imaging ,Electroencephalography ,Middle Aged ,Shock, Septic ,Magnetic Resonance Imaging ,Hospitals ,Body Fluids ,Survival Rate ,Electrophysiology ,Intensive Care Units ,Bioassays and Physiological Analysis ,Brain Electrophysiology ,Neurology ,Medicine ,Female ,Anatomy ,Research Article ,Critical Care ,Imaging Techniques ,Science ,Cognitive Neuroscience ,Neurophysiology ,Neuroimaging ,Research and Analysis Methods ,Disease-Free Survival ,Signs and Symptoms ,Diagnostic Medicine ,Neuropsychology ,Sepsis ,Humans ,Aged ,Neuropsychological Testing ,Electrophysiological Techniques ,Correction ,Biology and Life Sciences ,Health Care ,Health Care Facilities ,Lesions ,Cognitive Science ,Clinical Medicine ,Neuroscience - Abstract
Sepsis-associated encephalopathy (SAE) contributes to mortality and neurocognitive impairment of sepsis patients. Neurofilament (Nf) light (NfL) and heavy (NfH) chain levels as biomarkers for neuroaxonal injury were not evaluated in cerebrospinal fluid (CSF) and plasma of patients with sepsis-associated encephalopathy (SAE) before. We conducted a prospective, pilot observational study including 20 patients with septic shock and five patients without sepsis serving as controls. The assessment of SAE comprised a neuropsychiatric examination, electroencephalography (EEG), magnetic resonance imaging (MRI) and delirium screening methods including the confusion assessment method for the ICU (CAM-ICU) and the intensive care delirium screening checklist (ICDSC). CSF Nf measurements in sepsis patients and longitudinal plasma Nf measurements in all participants were performed on days 1, 3 and 7 after study inclusion. Plasma NfL levels increased in sepsis patients over time (p = 0.0063) and remained stable in patients without sepsis. Plasma NfL values were significantly higher in patients with SAE (p = 0.011), significantly correlated with the severity of SAE represented by ICDSC values (R = 0.534, p = 0.022) and correlated with a poorer functional outcome after 100 days (R = -0.535, p = 0.0003). High levels of CSF Nf were measured in SAE patients. CSF NfL levels were higher in non-survivors (p = 0.012) compared with survivors and correlated with days until death (R = -0.932, p
- Published
- 2019
14. The Effects of Thoracic Epidural Anesthesia on Hepatic Perfusion and Oxygenation in Healthy Pigs During General Anesthesia and Surgical Stress
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Vagts, Dierk A., Iber, Thomas, Puccini, Marcus, Szabo, Bela, Haberstroh, Jörg, Villinger, Florian, Geiger, Klaus, and Nöldge-Schomburg, Gabriele F. E.
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- 2003
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15. Extracorporeal Detoxification Using the Molecular Adsorbent Recirculating System for Critically Ill Patients with Liver Failure
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Mitzner, Steffen R., Stange, Jan, Klammt, Sebastian, Peszynski, Piotr, Schmidt, Reinhardt, and Nöldge-Schomburg, Gabriele
- Published
- 2001
16. Effects of bioreactor‐oxygenation during extracorporeal granulocytes treatment in septic patients
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Sauer, Martin, Richter, Georg, Altrichter, Jens, Wild, Thomas, Doß, Fanny, Mencke, Thomas, Ehler, Johannes, Doß, Sandra, Koch, Stephanie, Schubert, Anton, Nöldge-Schomburg, Gabriele, Mitzner, Steffen R., and Publica
- Abstract
A granulocyte bioreactor for the extracorporeal treatment was developed to enhance the immune cell function in patients with severe sepsis. The influence of oxygenation on the used cells was tested in a prospective clinical study. Ten patients with severe sepsis were treated twice with the granulocyte bioreactor. The used cells were screened for functionality; values of blood gases, glucose and lactate were obtained from the recirculating bioreactor circuit. Five patients were treated with an oxygenator setup (Oxy group), five without oxygenator (Non-Oxy group). The overall in-hospital mortality was 50%. Significantly lower values of oxygen saturation, partial oxygen pressure, lactate, oxyburst and phagocytosis were seen in the Non-Oxy group compared with the Oxy group in the bioreactor circuit. Further studies with this approach are encouraged and should focus on the influence of oxygenation on production of reactive oxygen species and cytokines of used cells.
- Published
- 2018
17. Impaired cell viability and functionality of hepatocytes after incubation with septic plasma
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Sauer, Martin, Haubner, Cristof, Richter, Georg, Ehler, Johannes, Mencke, Thomas, Mitzner, Steffen, Margraf, Stefan, Altrichter, Jens, Doss, Sandra, Nöldge-Schomburg, Gabriele, and Publica
- Subjects
inflammation ,liver failure ,cytotoxicity ,hepatocytes ,biosensing techniques - Abstract
Liver dysfunction (LD) and liver failure are associated with poor outcome in critically ill patients. In patients with severe sepsis or septic shock, LD occurred in nearly 19% of patients. An early diagnosis of LD at time of initial damage of the liver can lead to a better prognosis of these patients because an early start of therapy is possible. We performed a second prospective study with septic patients to test a new cell-based cytotoxicity device (biosensor) to evaluate clinical relevance for early diagnosis of LD and prognostic capacity. In the clinical study, 99 intensive care unit patients were included in two groups. From the patients of the septic group (n = 51, SG), and the control (non-septic) group [n = 49, control group (CG)] were drawn 20 ml blood at inclusion, after 3, and 7 days for testing with the biosensor. Patients' data were recorded for hospital survival, organ function, and demographic data, illness severity [acute physiology and chronic health evaluation (APACHE) II-, sepsis-related organ failure assessment (SOFA) scores], cytokines, circulating-free deoxyribonucleic acid/neutrophil-derived extracellular traps (cf-DNA/NETs), microbiological results, and pre-morbidity. For the developed cytotoxicity test, the human liver cell line HepG2/C3A was used. Patients' plasma was incubated in a microtiter plate assay with the test cells and after 6 days incubation the viability (trypan blue staining, XTT-test) and functionality (synthesis of albumin, cytochrome 1A2 activity) was analyzed. An impairment of viability and functionality of test cells was only seen in the SG compared with the CG. The plasma of non-survivors in the SG led to a more pronounced impairment of test cells than the plasma of survivors at inclusion. In addition, the levels of cf-DNA/NETs were significantly higher in the SG at inclusion, after 3, and after 7 days compared with the CG. The SG showed an in-hospital mortality of 24% and the values of bilirubin, APACHE II-, and SOFA scores were markedly higher at inclusion than in the CG. Hepatotoxicity of septic plasma was already detected with the liver cell-based biosensor at inclusion and also in the course of disease. The biosensor may be a tool for early diagnosis of LD in septic patients and may have prognostic relevance.
- Published
- 2018
18. Bioartificial therapy of sepsis
- Author
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Sauer, Martin, Altrichter, Jens, Haubner, Cristof, Pertschy, Annette, Wild, Thomas, Doß, Fanny, Mencke, Thomas, Thomsen, Maren, Ehler, Johannes, Henschel, Jörg, Doß, Sandra, Koch, Stephanie, Richter, Georg, Nöldge-Schomburg, Gabriele, Mitzner, Steffen R., and Publica
- Abstract
Purpose: Granulocyte transfusions have been used to treat immune cell dysfunction in sepsis. A granulocyte bioreactor for the extracorporeal treatment of sepsis was tested in a prospective clinical study focusing on the dosage of norepinephrine in patients and influence on dynamic and cell based liver tests during extracorporeal therapies. Methods and Patients: Ten patients with severe sepsis were treated twice within 72 h with the system containing granulocytes from healthy donors. Survival, physiologic parameters, extended hemodynamic measurement, and the indocyanine green plasma disappearance rate (PDR) were monitored. Plasma of patients before and after extracorporeal treatments were tested with a cell based biosensor for analysis of hepatotoxicity. Results: The observed mortality rate was 50% during stay in hospital. During the treatments, the norepinephrine-dosage could be significantly reduced while mean arterial pressure was stable. In the cell based analysis of hepatotoxicity, the viability and function of sensor-cells increased significantly during extracorporeal treatment in all patients and the PDR-values increased significantly between day 1 and day 7 only in survivors. Conclusion. The extracorporeal treatment with donor granulocytes showed promising effects on dosage of norepinephrine in patients, liver cell function, and viability in a cell based biosensor. Further studies with this approach are encouraged.
- Published
- 2016
19. Role of different replacement fluids during extracorporeal treatment in a pig model of sepsis
- Author
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Sauer, Martin, Altrichter, Jens, Mencke, Thomas, Klöhr, Sven, Thomsen, Maren, Kreutzer, Hans J., Nöldge-Schomburg, Gabriele, Mitzner, Steffen, and Publica
- Subjects
centrifugation ,colloids ,extracorporeal therapy ,septic shock ,plasma - Abstract
In an extracorporeal combination therapy, the impact of different replacement fluids on survival was tested in a bacterial sepsis model in pigs. In an animal study 19 pigs, weighing 7.5-11.1 kg, were included. All groups received an intravenous lethal dose of live Staphylococcus aureus over 1 h. The animals were treated by an extracorporeal circuit consisting of online centrifugation and subsequent plasma filtration for 4 h. The extracorporeal circuit was pre-filled with 400 mL replacement fluid. In the P0 group 100% hydroxyethyl starch 130/0.4 was used as replacement fluid; in the P30 group 30% pig plasma and 70% hydroxyethyl starch; and in the P100 group 100% pig plasma. The observation time was 7 days. All animals of the group P100 survived, while all animals of group P0 and five out of seven animals of the P30 group died during the observation time. Extracorporeal therapy consisting of online centrifugation and plasma filtration with 100% pig plasma as replacement fluid significantly improved survival in a pig model of sepsis. Further studies with this approach are encouraged.
- Published
- 2013
20. Impaired Cell Viability and Functionality of Hepatocytes After Incubation With Septic Plasma—Results of a Second Prospective Biosensor Study.
- Author
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Sauer, Martin, Haubner, Cristof, Richter, Georg, Ehler, Johannes, Mencke, Thomas, Mitzner, Steffen, Margraf, Stefan, Altrichter, Jens, Doß, Sandra, and Nöldge-Schomburg, Gabriele
- Subjects
LIVER cells ,SEPSIS - Abstract
Liver dysfunction (LD) and liver failure are associated with poor outcome in critically ill patients. In patients with severe sepsis or septic shock, LD occurred in nearly 19% of patients. An early diagnosis of LD at time of initial damage of the liver can lead to a better prognosis of these patients because an early start of therapy is possible. We performed a second prospective study with septic patients to test a new cell-based cytotoxicity device (biosensor) to evaluate clinical relevance for early diagnosis of LD and prognostic capacity. In the clinical study, 99 intensive care unit patients were included in two groups. From the patients of the septic group (
n = 51, SG), and the control (non-septic) group [n = 49, control group (CG)] were drawn 20 ml blood at inclusion, after 3, and 7 days for testing with the biosensor. Patients’ data were recorded for hospital survival, organ function, and demographic data, illness severity [acute physiology and chronic health evaluation (APACHE) II-, sepsis-related organ failure assessment (SOFA) scores], cytokines, circulating-free deoxyribonucleic acid/neutrophil-derived extracellular traps (cf-DNA/NETs), microbiological results, and pre-morbidity. For the developed cytotoxicity test, the human liver cell line HepG2/C3A was used. Patients’ plasma was incubated in a microtiter plate assay with the test cells and after 6 days incubation the viability (trypan blue staining, XTT-test) and functionality (synthesis of albumin, cytochrome 1A2 activity) was analyzed. An impairment of viability and functionality of test cells was only seen in the SG compared with the CG. The plasma of non-survivors in the SG led to a more pronounced impairment of test cells than the plasma of survivors at inclusion. In addition, the levels of cf-DNA/NETs were significantly higher in the SG at inclusion, after 3, and after 7 days compared with the CG. The SG showed an in-hospital mortality of 24% and the values of bilirubin, APACHE II-, and SOFA scores were markedly higher at inclusion than in the CG. Hepatotoxicity of septic plasma was already detected with the liver cell-based biosensor at inclusion and also in the course of disease. The biosensor may be a tool for early diagnosis of LD in septic patients and may have prognostic relevance. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
21. Translational evidence for two distinct patterns of neuroaxonal injury in sepsis: a longitudinal, prospective translational study.
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Ehler, Johannes, Barrett, Lucinda K., Taylor, Valerie, Groves, Michael, Scaravilli, Francesco, Wittstock, Matthias, Kolbaske, Stephan, Grossmann, Annette, Henschel, Jörg, Gloger, Martin, Sharshar, Tarek, Chretien, Fabrice, Gray, Francoise, Nöldge-Schomburg, Gabriele, Singer, Mervyn, Sauer, Martin, and Petzold, Axel
- Subjects
BRAIN abnormalities ,RAT anatomy ,BRAIN diseases ,ANIMALS ,AUTOPSY ,BIOLOGICAL models ,BRAIN ,ELECTROENCEPHALOGRAPHY ,INTENSIVE care units ,LONGITUDINAL method ,MAGNETIC resonance imaging ,NERVE tissue proteins ,NERVOUS system ,PROGNOSIS ,PROTEIN precursors ,RATS ,DISEASE complications - Abstract
Background: Brain homeostasis deteriorates in sepsis, giving rise to a mostly reversible sepsis-associated encephalopathy (SAE). Some survivors experience chronic cognitive dysfunction thought to be caused by permanent brain injury. In this study, we investigated neuroaxonal pathology in sepsis.Methods: We conducted a longitudinal, prospective translational study involving (1) experimental sepsis in an animal model; (2) postmortem studies of brain from patients with sepsis; and (3) a prospective, longitudinal human sepsis cohort study at university laboratory and intensive care units (ICUs). Thirteen ICU patients with septic shock, five ICU patients who died as a result of sepsis, fourteen fluid-resuscitated Wistar rats with fecal peritonitis, eleven sham-operated rats, and three human and four rat control subjects were included. Immunohistologic and protein biomarker analysis were performed on rat brain tissue at baseline and 24, 48, and 72 h after sepsis induction and in sham-treated rats. Immunohistochemistry was performed on human brain tissue from sepsis nonsurvivors and in control patients without sepsis. The clinical diagnostics of SAE comprised longitudinal clinical data collection and magnetic resonance imaging (MRI) and electroencephalographic assessments. Statistical analyses were performed using SAS software (version 9.4; SAS Institute, Inc., Cary, NC, USA). Because of non-Gaussian distribution, the nonparametric Wilcoxon test general linear models and the Spearman correlation coefficient were used.Results: In postmortem rat and human brain samples, neurofilament phosphoform, β-amyloid precursor protein, β-tubulin, and H&E stains distinguished scattered ischemic lesions from diffuse neuroaxonal injury in septic animals, which were absent in controls. These two patterns of neuroaxonal damage were consistently found in septic but not control human postmortem brains. In experimental sepsis, the time from sepsis onset correlated with tissue neurofilament levels (R = 0.53, p = 0.045) but not glial fibrillary acidic protein. Of 13 patients with sepsis who had clinical features of SAE, MRI detected diffuse axonal injury in 9 and ischemia in 3 patients.Conclusions: Ischemic and diffuse neuroaxonal injury to the brain in experimental sepsis, human postmortem brains, and in vivo MRI suggest these two distinct lesion types to be relevant. Future studies should be focused on body fluid biomarkers to detect and monitor brain injury in sepsis. The relationship of neurofilament levels with time from sepsis onset may be of prognostic value.Trial Registration: ClinicalTrials.gov, NCT02442986 . Registered on May 13, 2015. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
22. Bioartificial Therapy of Sepsis: Changes of Norepinephrine-Dosage in Patients and Influence on Dynamic and Cell Based Liver Tests during Extracorporeal Treatments.
- Author
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Sauer, Martin, Altrichter, Jens, Haubner, Cristof, Pertschy, Annette, Wild, Thomas, Doß, Fanny, Mencke, Thomas, Thomsen, Maren, Ehler, Johannes, Henschel, Jörg, Doß, Sandra, Koch, Stephanie, Richter, Georg, Nöldge-Schomburg, Gabriele, and Mitzner, Steffen R.
- Subjects
SEPTICEMIA treatment ,APACHE (Disease classification system) ,ARTERIES ,ARTIFICIAL blood circulation ,BLOOD pressure ,CELL culture ,CELL physiology ,CYTOKINES ,GRANULOCYTES ,HEMODYNAMICS ,HEPATOTOXICOLOGY ,LIVER function tests ,LONGITUDINAL method ,NORADRENALINE ,PROBABILITY theory ,RESEARCH funding ,PRE-tests & post-tests ,DATA analysis software ,DESCRIPTIVE statistics ,MANN Whitney U Test ,KRUSKAL-Wallis Test ,FRIEDMAN test (Statistics) - Abstract
Purpose. Granulocyte transfusions have been used to treat immune cell dysfunction in sepsis. A granulocyte bioreactor for the extracorporeal treatment of sepsis was tested in a prospective clinical study focusing on the dosage of norepinephrine in patients and influence on dynamic and cell based liver tests during extracorporeal therapies. Methods and Patients. Ten patients with severe sepsis were treated twice within 72 h with the system containing granulocytes from healthy donors. Survival, physiologic parameters, extended hemodynamic measurement, and the indocyanine green plasma disappearance rate (PDR) were monitored. Plasma of patients before and after extracorporeal treatments were tested with a cell based biosensor for analysis of hepatotoxicity. Results. The observed mortality rate was 50% during stay in hospital. During the treatments, the norepinephrine-dosage could be significantly reduced while mean arterial pressure was stable. In the cell based analysis of hepatotoxicity, the viability and function of sensor-cells increased significantly during extracorporeal treatment in all patients and the PDR-values increased significantly between day 1 and day 7 only in survivors. Conclusion. The extracorporeal treatment with donor granulocytes showed promising effects on dosage of norepinephrine in patients, liver cell function, and viability in a cell based biosensor. Further studies with this approach are encouraged. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
23. Awake Extracorporeal Membrane Oxygenation (ECMO) as Bridge to Recovery After Left Main Coronary Artery Occlusion: A Promising Concept of Haemodynamic Support in Cardiogenic Shock
- Author
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Alozie, Anthony, Kische, Stephan, Birken, Thomas, Kaminski, Alexander, Westphal, Bernd, Nöldge-Schomburg, Gabriele, Ince, Hüseyin, and Steinhoff, Gustav
- Published
- 2014
- Full Text
- View/download PDF
24. Hydrocortisone Reduces the Beneficial Effects of Toll-Like Receptor 2 Deficiency on Survival in a Mouse Model of Polymicrobial Sepsis.
- Author
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Bergt, Stefan, Wagner, Nana-Maria, Heidrich, Manja, Butschkau, Antje, Nöldge-Schomburg, Gabriele E. F., Vollmar, Brigitte, and Roesner, Jan P.
- Published
- 2013
- Full Text
- View/download PDF
25. Design and implementation of a control system reflecting the level of analgesia during general anesthesia.
- Author
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Janda, Matthias, Schubert, Agnes, Bajorat, Jörn, Hofmockel, Rainer, Nöldge-Schomburg, Gabriele F.E., Lampe, Bernhard P., and Simanski, Olaf
- Published
- 2013
- Full Text
- View/download PDF
26. Plasma Separation by Centrifugation and Subsequent Plasma Filtration: Impact on Survival in a Pig Model of Sepsis.
- Author
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Sauer, Martin, Altrichter, Jens, Mencke, Thomas, Klöhr, Sven, Thomsen, Maren, Kreutzer, Hans J., Nöldge-Schomburg, Gabriele, and Mitzner, Steffen R.
- Abstract
The impact on survival of a combination of plasma separation by centrifugation and subsequent plasma filtration was tested in a bacterial sepsis model in pigs. In this animal study 19 pigs were included. Groups II and III received an intravenous lethal dose of live Staphylococcus aureus over 1 h; group I received saline (non-septic control-NC). Groups I and II were treated by an extracorporeal circuit consisting of online centrifugation and subsequent plasma filtration (group II: treated group-TG) for 4 h; group III had no specific treatment (septic control, SC). The observation time was 7 days. All animals of group I (NC) and group II (TG) survived, while all animals of group III (SC) died during the observation time. Extracorporeal therapy with online centrifugation and plasma filtration significantly improved survival in a pig model of sepsis. Further studies with this approach are encouraged. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
27. THERAPEUTIC INJECTION OF PARP INHIBITOR INO-1001 PRESERVES CARDIAC FUNCTION IN PORCINE MYOCARDIAL ISCHEMIA AND REPERFUSION WITHOUT REDUCING INFARCT SIZE.
- Author
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Roesner, Jan P., Mersmann, Jan, Bergt, Stefan, Bohnenberg, Karl, Barthuber, Carmen, Szabo, Csaba, Nöldge-Schomburg, Gabriele E. F., and Zacharowski, Kai
- Published
- 2010
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- View/download PDF
28. A COMPREHENSIVE STUDY OF SURVIVAL, TISSUE DAMAGE, AND NEUROLOGICAL DYSFUNCTION IN A MURINE MODEL OF CARDIOPULMONARY RESUSCITATION AFTER POTASSIUM-INDUCED CARDIAC ARREST.
- Author
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Menzebach, Axel, Bergt, Stefan, Waldthausen, Philine Von, Dinu, Christian, Nöldge-Schomburg, Gabriele, and Vollmar, Brigitte
- Published
- 2010
- Full Text
- View/download PDF
29. Safety Evaluation for a Cell-based Immune Support System in an Ex Vivo Rat Model of Gram-negative Sepsis.
- Author
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Sauer, Martin, Altrichter, Jens, Kreutzer, Hans-Jürgen, Schmidt, Heidrun, Nöldge-Schomburg, Gabriele, Schmidt, Reinhard, and Mitzner, Steffen R
- Abstract
Granulocyte dysfunction is a central component of immunodeficiency in septic patients. Granulocyte transfusions appear to be pathophysiologically useful; however, they cause unwanted side-effects in the lungs and other organs. This study evaluates the safety of an extracorporeal immune support system with granulocytic cells in a rat model of Gram-negative sepsis. Three groups of male CD rats received either saline (control group, I), a dose of Escherichia coli O7:K1 lethal to 90% of the animals (LD90) (septic group, II), or an LD90 dose of E. coli that was incubated with the human promyelocytic leukemia cell line (HL-60) (differentiated into the granulocytic direction) for 20 min prior to infusion (second septic group, III). The animals were observed for seven days. Pre-treatment with HL-60 cells resulted in no adverse effects in the group III animals. Significantly lower bacterial counts and endotoxin levels in the plasma were detected after 24 h as compared to group II ( P < 0.05). Group III animals had better weight gain and more stable hemodynamics than group II animals ( P < 0.01). Seven day survival was 0/8 in group II, 6/8 in group III, and 8/9 in group I (log–rank test: II–III: P < 0.001). The data suggest that extracorporeal use of granulocytes allows the therapeutic use of these cells while avoiding unwanted effects resulting from direct contact to internal organs. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
30. A surgical technique for catheterization of the sagittal sinus in pigs.
- Author
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Schütze, Michael, Janda, Matthias, Bajorat, Jörn, Piek, Juergen, Nöldge-Schomburg, Gabriele F. E., and Hofmockel, Rainer
- Subjects
VETERINARY medicine ,LABORATORY animals ,ANIMAL experimentation ,BLOOD gases ,OPERATIVE surgery - Abstract
The purpose of our study was to describe an efficient, reliable and inexpensive surgical method for cerebral venous blood gas sampling in acutely instrumented pigs in a research setting. Parameters from the blood samples are used to monitor brain perfusion and oxygenation in different animal models. To the authors' knowledge, this is the first detailed description of an accurate surgical technique for catheterization of the sagittal sinus in pigs. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
31. A novel visually CO_{2} controlled alveolar breath sampling technique.
- Author
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Birken, Thomas, Schubert, Jochen, Miekisch, Wolfram, and Nöldge-Schomburg, Gabriele
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BLOOD gases ,GASES ,ARTIFICIAL respiration ,RESPIRATORY therapy ,PATIENTS - Abstract
Background: A crucial issue in the analysis of exhaled breath is the collection of gaseous samples. The analysis of pure alveolar gas is the method of choice if contamination of samples is to be minimized. Monitoring of expired CO_{2} can be used to identify alveolar gas. The purpose of this study was to evaluate a bed side version of this technique using visual CO_{2} control by means of a capnometer. Methods: 22 mechanically ventilated patients of an ICU were enrolled into the study. Alveolar and mixed expiratory gas, and arterial blood were sampled. PCO_{2} in blood and gas was determined in a blood gas analyzer. End tidal PCO_{2} was monitored in all patients by a fast responding main stream capnometry. Taking the gaseous samples was visually synchronized with the expired CO_{2}. Results: Alveolar CO_{2} contents measured during two different respiratory cycles were identical (p 0.86). The variation of the CO_{2} content during 10 measurements in one patient was lower than 4%. Arterial PCO_{2}, PCO_2 in alveolar gas and end tidal PCO_{2} showed positive correlation. Conclusions: The visually CO_{2}-controlled sampling technique of alveolar gas is a reliable and reproducible method. It represents an important step in simplifying and standardizing breath analysis. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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32. Sickle Cell Anemia: Conclusions from a Forensic Case Report of a Young African Woman Who Died After Anesthesia.
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Hammer, Ulrich, Wegener, Rudolf, Nizze, Horst, Wöhlke, Gunther, Kruse, Christine, Dworniczak, Bernd, Kühn-Velten, W. Nikolaus, Nöldge-Schomburg, Gabriele, Hofmockel, Rainer, and Jonas, Ludwig
- Subjects
ANESTHESIA complications ,PREANESTHETIC medication ,FORENSIC serology ,ELECTROPHORESIS ,ELECTRON microscopy ,DISEASES in women - Abstract
A 20-year old African woman underwent anesthesia for interruption of an unwanted pregnancy. As a consequence of the anesthesia, she went into coma because of an as yet unknown and untested homozygotic state of sickle cell anemia. Her vital functions were maintained for more than 1 year by intensive medicine, but she died finally in multiorgan failure and aspiration pneumonia. Because of the complications under anesthesia and the missing preanesthetic test for hemoglobinopathy, autopsy was conducted in the forensic medicine department and not in the department of pathology. The sickle cell disease was diagnosed by electrophoresis of the blood, by molecular detection of mutation in the hemoglobin gene, as well as by postmortem light and electron microscopy. Sickle cells were found in capillaries of brain, liver, lung, bone marrow, and spleen. Electrophoretic analysis revealed 80.2% HbS in addition to 3.2% HbA2 and 16.6% HbF, whereas no HbA0 could be detected in blood, confirming the homozygosity of sickle cell anemia. Because of sickle cell crisis, occluded blood vessels, and severe brain cortex necrosis, the patient died in spite of reanimation and intensive medicine. This case demonstrates that it is still important to realize the possibility of this disease and diagnostic obstacles even in regions where its manifestation is not endemic, as in Northern and Central Europe. [ABSTRACT FROM AUTHOR]
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- 2006
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33. Impact of Toll-Like Receptor 2 Deficiency on Survival and Neurological Function after Cardiac Arrest: A Murine Model of Cardiopulmonary Resuscitation.
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Bergt, Stefan, Güter, Anne, Grub, Andrea, Wagner, Nana-Maria, Beltschany, Claudia, Langner, Sönke, Wree, Andreas, Hildebrandt, Steve, Nöldge-Schomburg, Gabriele, Vollmar, Brigitte, and Roesner, Jan P.
- Subjects
TOLL-like receptors ,CARDIAC arrest ,CARDIOPULMONARY resuscitation ,INFLAMMATION ,REPERFUSION injury ,IMMUNOGLOBULINS ,LABORATORY mice - Abstract
Background:Cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR) is associated with poor survival rate and neurofunctional outcome. Toll-like receptor 2 (TLR2) plays an important role in conditions of sterile inflammation such as reperfusion injury. Recent data demonstrated beneficial effects of the administration of TLR2-blocking antibodies in ischemia/reperfusion injury. In this study we investigated the role of TLR2 for survival and neurofunctional outcome after CA/CPR in mice. Methods:Female TLR2-deficient (TLR2
-/- ) and wild type (WT) mice were subjected to CA for eight min induced by intravenous injection of potassium chloride and CPR by external chest compression. Upon the beginning of CPR, n = 15 WT mice received 5 µg/g T2.5 TLR2 inhibiting antibody intravenously while n = 30 TLR2-/- and n = 31 WT controls were subjected to injection of normal saline. Survival and neurological outcome were evaluated during a 28-day follow up period. Basic neurological function, balance, coordination and overall motor function as well as spatial learning and memory were investigated, respectively. In a separate set of experiments, six mice per group were analysed for cytokine and corticosterone serum levels eight hours after CA/CPR. Results:TLR2 deficiency and treatment with a TLR2 blocking antibody were associated with increased survival (77% and 80% vs. 51% of WT control; both P < 0.05). Neurofunctional performance was less compromised in TLR2-/- and antibody treated mice. Compared to WT and antibody treated mice, TLR2-/- mice exhibited reduced IL-6 (both P < 0.05) but not IL-1β levels and increased corticosterone plasma concentrations (both P < 0.05). Conclusion:Deficiency or functional blockade of TLR2 is associated with increased survival and improved neurofunctional outcome in a mouse model of CA/CPR. Thus, TLR2 inhibition could provide a novel therapeutic approach for reducing mortality and morbidity after cardiac arrest and cardiopulmonary resuscitation. [ABSTRACT FROM AUTHOR]- Published
- 2013
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34. The Treatment of Patients With Severe and Multiple Traumatic Injuries.
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Neugebauer, Edmund A. M., Waydhas, Christian, Lendemans, Sven, Rixen, Dieter, Eikermann, Michaela, Nöldge-Schomburg, Gabriele, Van Aken, Hugo, Böttiger, Bernd W., Siebert, Hartmut, Pohlemann, and Bouillon, Bertil
- Abstract
A letter to the editor is presented in response to the article "The Treatment of Patients With Severe and Multiple Traumatic Injuries," by the authors Edmund A. M. Neugebauer, Christian Waydhas, Sven Lendemans, Dieter Rixen, Michaela Eikermann, and Tim Pohlemann.
- Published
- 2012
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35. Extracorporeal cell therapy of septic shock patients with donor granulocytes: a pilot study.
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Altrichter, Jens, Sauer, Martin, Kaftan, Katharina, Birken, Thomas, Gloger, Doris, Gloger, Martin, Henschel, Jörg, Hickstein, Heiko, Klar, Ernst, Koball, Sebastian, Pertschy, Annette, Nöldge-Schomburg, Gabriele, Vagts, Dierk A, and Mitzner, Steffen R
- Abstract
Introduction: Neutrophil granulocytes are the first defense line in bacterial infections. However, granulocytes are also responsible for severe local tissue impairment. In order to use donor granulocytes, but at the same time to avoid local side effects, we developed an extracorporeal immune support system. This first-in-man study investigated whether an extracorporeal plasma treatment with a granulocyte bioreactor is tolerable in patients with septic shock. A further intention was to find suitable efficacy end-points for subsequent controlled trials.Methods: The trial was conducted as a prospective uncontrolled clinical phase I/II study with 28-day follow-up at three university hospital intensive care units. Ten consecutive patients (five men, five women, mean age 60.3 ± 13.9 standard deviation (SD) years) with septic shock with mean ICU entrance scores of Acute Physiology and Chronic Health Evaluation (APACHE) II of 29.9 ± 7.2 and of Simplified Acute Physiology Score (SAPS) II of 66.2 ± 19.5 were treated twice within 72 hours for a mean of 342 ± 64 minutes/treatment with an extracorporeal bioreactor containing 1.41 ± 0.43 × 10E10 granulocytes from healthy donors. On average, 9.8 ± 2.3 liters separated plasma were treated by the therapeutic donor cells. Patients were followed up for 28 days.Results: Tolerance and technical safety during treatment, single organ functions pre/post treatment, and hospital survival were monitored. The extracorporeal treatments were well tolerated. During the treatments, the bacterial endotoxin concentration showed significant reduction. Furthermore, noradrenaline dosage could be significantly reduced while mean arterial pressure was stable. Also, C-reactive protein, procalcitonin, and human leukocyte antigen DR (HLA-DR) showed significant improvement. Four patients died in the hospital on days 6, 9, 18 and 40. Six patients could be discharged.Conclusions: The extracorporeal treatment with donor granulocytes appeared to be well tolerated and showed promising efficacy results, encouraging further studies.Trial Registration: ClinicalTrials.gov Identifier: NCT00818597. [ABSTRACT FROM AUTHOR]- Published
- 2011
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36. Diagnostic value of NT-proCNP compared to NSE and S100B in cerebrospinal fluid and plasma of patients with sepsis-associated encephalopathy.
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Ehler, Johannes, Saller, Thomas, Wittstock, Matthias, Rommer, Paulus S., Chappell, Daniel, Zwissler, Bernhard, Grossmann, Annette, Richter, Georg, Reuter, Daniel A., Nöldge-Schomburg, Gabriele, and Sauer, Martin
- Subjects
- *
CEREBROSPINAL fluid , *BARTHEL Index , *BRAIN natriuretic factor , *SEPSIS , *DELIRIUM , *MAGNETIC resonance imaging - Abstract
Highlights • Plasma NT-proCNP levels are highly elevated in sepsis patients with SAE. • Plasma NT-proCNP levels might be of clinical value for the detection of SAE. • CSF and plasma NT-proCNP levels correlate in patients with SAE. • This correlation suggests a link between systemic and neuroinflammation in SAE. • Plasma NT-proCNP measurement might be superior to S100B and NSE in SAE. Abstract Sepsis-associated encephalopathy (SAE) has significant impact on the neurocognitive outcome of sepsis survivors. This study was conducted to analyze the amino-terminal propeptide of the C-type natriuretic peptide (NT-proCNP) as a biomarker for SAE in comparison to neuron-specific enolase (NSE) and S100B protein. Cerebrospinal fluid (CSF) and plasma samples from twelve septic patients with SAE and nine non-septic controls without encephalopathy were analyzed. The assessment of SAE comprised a neuropsychiatric examination, delirium screening using the confusion assessment method in the ICU (CAM-ICU) and magnetic resonance imaging (MRI) in all participants. NSE, S100B and NT-proCNP were measured in plasma at study days 1, 3 and 7 in sepsis patients, once in controls and once in the CSF of both groups. The long-term outcome was assessed using the validated Barthel index (BI). Plasma NT-proCNP levels were significantly higher in the sepsis cohort compared to controls with peak concentrations at study day 1 (10.1 ± 6.6 pmol/l vs. 3.3 ± 0.9 pmol/l; p < 0.01) and a decrease over time. Plasma NT-proCNP levels at day 7 correlated with NT-proCNP in CSF (r = 0.700, p < 0.05). A comparable decrease of significantly higher plasma S100B values in sepsis patients compared to controls was observed. Plasma NSE levels were not significantly different between both groups. CSF NT-proCNP levels just tended to be higher in sepsis patients compared to controls and tended to be higher in patients with septic brain lesions seen on MRI. In the sepsis cohort CSF NT-proCNP levels correlated with CSF Interleukin-6 (IL-6) levels (r = 0.616, p < 0.05) and systemic inflammation represented by high plasma procalcitonin (PCT) levels at day 3 (r = 0.727, p < 0.05). The high peak concentration of plasma NT-proCNP in the early phase of sepsis might help to predict the emergence of SAE during the further course of disease. NT-proCNP in plasma might, in contrast to CSF, indicate neurological impairment in patients with SAE. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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37. Correction: The prognostic value of neurofilament levels in patients with sepsis-associated encephalopathy - A prospective, pilot observational study.
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Ehler J, Petzold A, Wittstock M, Kolbaske S, Gloger M, Henschel J, Heslegrave A, Zetterberg H, Lunn MP, Rommer PS, Grossmann A, Sharshar T, Richter G, Nöldge-Schomburg G, and Sauer M
- Abstract
[This corrects the article DOI: 10.1371/journal.pone.0211184.].
- Published
- 2019
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38. Effects of Bioreactor-Oxygenation During Extracorporeal Granulocytes Treatment in Septic Patients.
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Sauer M, Richter G, Altrichter J, Wild T, Doß F, Mencke T, Ehler J, Doß S, Koch S, Schubert A, Nöldge-Schomburg G, and Mitzner SR
- Subjects
- Adult, Aged, Blood Gas Analysis, Cytokines metabolism, Glucose metabolism, Hospital Mortality, Humans, Lactates metabolism, Male, Middle Aged, Oxygen metabolism, Prospective Studies, Reactive Oxygen Species metabolism, Sepsis immunology, Sepsis physiopathology, Bioreactors, Extracorporeal Circulation methods, Granulocytes metabolism, Sepsis therapy
- Abstract
A granulocyte bioreactor for the extracorporeal treatment was developed to enhance the immune cell function in patients with severe sepsis. The influence of oxygenation on the used cells was tested in a prospective clinical study. Ten patients with severe sepsis were treated twice with the granulocyte bioreactor. The used cells were screened for functionality; values of blood gases, glucose and lactate were obtained from the recirculating bioreactor circuit. Five patients were treated with an oxygenator setup (Oxy group), five without oxygenator (Non-Oxy group). The overall in-hospital mortality was 50%. Significantly lower values of oxygen saturation, partial oxygen pressure, lactate, oxyburst and phagocytosis were seen in the Non-Oxy group compared with the Oxy group in the bioreactor circuit. Further studies with this approach are encouraged and should focus on the influence of oxygenation on production of reactive oxygen species and cytokines of used cells., (© 2018 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)
- Published
- 2018
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39. Toll-like receptor 2-blocking antibodies promote angiogenesis and induce ERK1/2 and AKT signaling via CXCR4 in endothelial cells.
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Wagner NM, Bierhansl L, Nöldge-Schomburg G, Vollmar B, and Roesner JP
- Subjects
- Animals, Cells, Cultured, Chemokine CXCL12 metabolism, Endothelial Cells cytology, Endothelial Cells immunology, Endothelial Cells metabolism, Hindlimb blood supply, Ischemia immunology, Ischemia metabolism, Ischemia physiopathology, Mice, Mice, Knockout, Muscle, Skeletal blood supply, Peripheral Arterial Disease metabolism, Peripheral Arterial Disease physiopathology, Proto-Oncogene Proteins c-akt metabolism, RNA, Small Interfering genetics, Receptors, CXCR4 genetics, Receptors, CXCR4 immunology, Toll-Like Receptor 2 genetics, Toll-Like Receptor 2 metabolism, p38 Mitogen-Activated Protein Kinases metabolism, Antibodies, Blocking pharmacology, MAP Kinase Signaling System immunology, Neovascularization, Physiologic immunology, Peripheral Arterial Disease immunology, Receptors, CXCR4 metabolism, Toll-Like Receptor 2 immunology
- Abstract
Objective: Toll-like receptor 2 (TLR2) inhibition by function blocking antibodies (ABs) is associated with enhanced preservation of endothelial cell function during vascular disease. In the present study, we investigated the capacity of TLR2-blocking ABs to modulate the angiogenic response of endothelial cells in vitro and in vivo., Approach and Results: Incubation of endothelial cells with mono- or polyclonal anti-TLR2 ABs resulted in increased tube formation, sprouting, and migration of endothelial cells compared with controls. In a mouse model of hindlimb ischemia, using TLR2-deficient or anti-TLR2 AB-treated wild-type mice resulted in increased new capillary formation and enhanced reperfusion. The effects of anti-TLR2 ABs were similar to those exerted by stromal cell-derived factor-1, and we show that anti-TLR2 ABs yet not TLR2 ligands lead to comparable activation of extracellular signal-regulated kinase1/2 and AKT but not p38 mitogen-activated protein kinase as activation of the CXCR4 canonical signal transduction pathways by stromal cell-derived factor-1. Immunoprecipitation of TLR2 revealed that anti-TLR2 ABs initiate an association of TLR2 with CXCR4 and mitogen-activated protein kinase activation. The proangiogenic properties of anti-TLR2 ABs were abolished by both G-protein inhibition and CXCR4 knockdown in endothelial cells., Conclusions: Our results provide evidence for a proangiogenic effect of TLR2-blocking ABs on endothelial cells in vitro and in vivo. They identify a novel molecular mechanism linking TLR2 to angiogenic processes that is independent from the activation of inflammatory cascades and further support the concept of a beneficial effect of TLR2 inhibition for endothelial cell function in vascular disease.
- Published
- 2013
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40. Design and implementation of a control system reflecting the level of analgesia during general anesthesia.
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Janda M, Schubert A, Bajorat J, Hofmockel R, Nöldge-Schomburg GF, Lampe BP, and Simanski O
- Subjects
- Adult, Algorithms, Analgesics, Opioid administration & dosage, Anesthetics, General administration & dosage, Feedback, Female, Humans, Male, Middle Aged, Remifentanil, Reproducibility of Results, Sensitivity and Specificity, Treatment Outcome, Anesthesia, General methods, Artificial Intelligence, Blood Pressure Determination methods, Drug Therapy, Computer-Assisted methods, Electrocardiography methods, Monitoring, Intraoperative methods, Piperidines administration & dosage
- Abstract
Introduction: Measuring and ensuring an adequate level of analgesia in patients are of increasing interest in the area of automated drug delivery during general anesthesia. Therefore, the aim of this investigation was to develop a control system that may reflect the intraoperative analgesia value. Our hypothesis was that a feedback controller could be applied in clinical practice safely and at an adequate quality of analgesia. The purpose of this study was to evaluate the practical feasibility of such a system in a clinical setting., Methods: The control system for the level of analgesia described in this paper relies on a parameter combination of heart rate variability (HRV), heart rate (HR), and blood pressure (mean arterial pressure, MAP), which serve as input variables for an expert system. For this fuzzy system, the experience of the participating anesthesiologists was translated into a set of fuzzy rules. In a pilot trial, the control system for automated titration of remifentanil, a short-acting opioid, was tested combined with a closed-loop propofol infusion system for hypnosis. Ten adult patients (4 women, 6 men), aged 22-52 years (median, 45 years; range, 29-49 years), with an American Society of Anesthesiologists physical status class I or II and who were scheduled for elective trauma surgery in a supine position were enrolled in this prospective trial. The precision of the system was calculated using internationally defined performance parameters., Results: There was no human intervention necessary during the computer-controlled administration of propofol and remifentanil, and operating conditions were satisfactory in all patients. All patients assessed the quality of anesthesia as "good" to "very good". Median performance error, median absolute performance error, and wobble for HR and MAP during maintenance of anesthesia were -8.98 (5.32), 10.08 (4.17), and 2.68 (1.29) and -4.51 (12.73), 13.63 (2.27), and 3.90 (2.08) [mean (SD)], respectively., Conclusion: The control system, reflecting the level of analgesia during general anesthesia designed and evaluated in this study, allows for a clinically practical, nearly fully automated infusion of an opioid during medium-length surgical procedures with acceptable technical requirements and an adequate precision.
- Published
- 2013
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41. Role of different replacement fluids during extracorporeal treatment in a pig model of sepsis.
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Sauer M, Altrichter J, Mencke T, Klöhr S, Thomsen M, Kreutzer HJ, Nöldge-Schomburg G, and Mitzner SR
- Subjects
- Animals, Disease Models, Animal, Female, Hydroxyethyl Starch Derivatives administration & dosage, Plasma Substitutes administration & dosage, Sepsis microbiology, Staphylococcal Infections microbiology, Staphylococcus aureus isolation & purification, Survival Rate, Swine, Extracorporeal Circulation methods, Fluid Therapy methods, Sepsis therapy, Staphylococcal Infections therapy
- Abstract
In an extracorporeal combination therapy, the impact of different replacement fluids on survival was tested in a bacterial sepsis model in pigs. In an animal study 19 pigs, weighing 7.5-11.1 kg, were included. All groups received an intravenous lethal dose of live Staphylococcus aureus over 1 h. The animals were treated by an extracorporeal circuit consisting of online centrifugation and subsequent plasma filtration for 4 h. The extracorporeal circuit was pre-filled with 400 mL replacement fluid. In the P0 group 100% hydroxyethyl starch 130/0.4 was used as replacement fluid; in the P30 group 30% pig plasma and 70% hydroxyethyl starch; and in the P100 group 100% pig plasma. The observation time was 7 days. All animals of the group P100 survived, while all animals of group P0 and five out of seven animals of the P30 group died during the observation time. Extracorporeal therapy consisting of online centrifugation and plasma filtration with 100% pig plasma as replacement fluid significantly improved survival in a pig model of sepsis. Further studies with this approach are encouraged., (© 2012 The Authors. Therapeutic Apheresis and Dialysis © 2012 International Society for Apheresis.)
- Published
- 2013
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42. Correspondence (letter to the editor): Team Leadership in the emergency room.
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Nöldge-Schomburg G, Van Aken H, and Böttiger BW
- Subjects
- Humans, Emergency Medical Services standards, Multiple Trauma diagnosis, Multiple Trauma therapy, Practice Guidelines as Topic, Traumatology standards
- Published
- 2012
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43. The neuronal guidance protein netrin-1 reduces alveolar inflammation in a porcine model of acute lung injury.
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Mutz C, Mirakaj V, Vagts DA, Westermann P, Waibler K, König K, Iber T, Nöldge-Schomburg G, and Rosenberger P
- Subjects
- Acute Lung Injury drug therapy, Animals, Cell Movement drug effects, Cell Movement physiology, Disease Models, Animal, Female, Inflammation pathology, Inflammation prevention & control, Nerve Growth Factors administration & dosage, Netrin-1, Neurons drug effects, Pulmonary Alveoli drug effects, Swine, Tumor Suppressor Proteins administration & dosage, Acute Lung Injury pathology, Nerve Growth Factors physiology, Neurons pathology, Pulmonary Alveoli pathology, Tumor Suppressor Proteins physiology
- Abstract
Introduction: Acute lung injury (ALI) is an inflammatory disorder of pulmonary or extrapulmonary origin. We have previously demonstrated that netrin-1 dampens murine ALI, and in an attempt to advance this finding into future clinical practice we evaluated whether netrin-1 would reduce alveolar inflammation during porcine ALI., Methods: This was a controlled in vivo experimental study in pigs. We induced ALI through lipoploysaccharide (LPS) infusion (50 μg/kg) for 2 hours. Following this, we exposed animals to either vehicle, intravenous netrin-1 (netrin-1 i.v.) or inhaled netrin-1 (netrin-1 inh.). Serum samples and bronchoalveolar lavage (BAL) were obtained to determine levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, interleukin-6 and interleukin-8 at baseline and 6 hours following treatment. Myeloperoxidase activity (MPO) and protein levels were determined in the BAL, and tissue samples were obtained for histological evaluation. Finally, animals were scanned with spiral CT., Results: Following LPS infusion, animals developed acute pulmonary injury. Serum levels of TNF-α and IL-6 were significantly reduced in the netrin-1 i.v. group. BAL demonstrated significantly reduced cytokine levels 6 hours post-netrin-1 treatment (TNF-α: vehicle 633 ± 172 pg/ml, netrin-1 i.v. 84 ± 5 pg/ml, netrin-1 inh. 168 ± 74 pg/ml; both P < 0.05). MPO activity and protein content were significantly reduced in BAL samples from netrin-1-treated animals. Histological sections confirmed reduced inflammatory changes in the netrin-1-treated animals. Computed tomography corroborated reduced pulmonary damage in both netrin-1-treated groups., Conclusions: We conclude that treatment with the endogenous anti-inflammatory protein netrin-1 reduces pulmonary inflammation during the initial stages of ALI and should be pursued as a future therapeutic option.
- Published
- 2010
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44. Bbeta15-42 (FX06) reduces pulmonary, myocardial, liver, and small intestine damage in a pig model of hemorrhagic shock and reperfusion.
- Author
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Roesner JP, Petzelbauer P, Koch A, Tran N, Iber T, Vagts DA, Scheeren TW, Vollmar B, Nöldge-Schomburg GE, and Zacharowski K
- Subjects
- Animals, Humans, Lung Injury physiopathology, Male, Models, Animal, Reperfusion Injury physiopathology, Shock, Hemorrhagic physiopathology, Swine, Fibrin Fibrinogen Degradation Products therapeutic use, Heart Injuries prevention & control, Intestine, Small injuries, Liver injuries, Lung Injury prevention & control, Peptide Fragments therapeutic use, Reperfusion Injury prevention & control, Shock, Hemorrhagic drug therapy
- Abstract
Objective: The fibrin-derived peptide Bbeta15-42 (also called FX06) has been shown to reduce myocardial infarct size following ischemia/reperfusion. Hemorrhagic shock (HS) followed by volume resuscitation represents a similar scenario, whereby a whole organism is vulnerable to reperfusion injury., Design: We subjected male farm-bred landrace pigs ( approximately 30 kg) to HS by withdrawing blood to a mean arterial pressure of 40 mm Hg for 60 minutes. Pigs were then resuscitated with shed blood and crystalloids for 60 minutes, and at this time, FX06 (2.4 mg/kg, n = 8) or vehicle control (phosphate buffered saline; 2.4 mg/kg, n = 7) was injected as an intravenous bolus., Setting: University hospital laboratory., Subjects: Anesthetized male farm-bred landrace pigs., Measurements and Main Results: Data are presented as mean +/- sd. Five hours after resuscitation, controls presented acute lung injury (Pao2/Fio2-ratio <300 mm Hg; extra-vascular lung water index (marker for lung injury): 9.0 +/- 1.8 mL/kg) and myocardial dysfunction/damage (cardiac index: 4.3 +/- 0.25 L/min/m; stroke volume index: 30 +/- 6 mL/m; cardiac TnT levels: 0.58 +/- 0.25 ng/mL). In contrast, FX06-treated animals showed significantly improved pulmonary and circulatory function (Pao2/Fio2-ratio >*400 mm Hg; extra-vascular lung water index: *5.2 +/- 2.1 mL/kg, cardiac index: *6.3 +/- 1.4 L/min/m; stroke volume index: *51 +/- 11 mL/m; cardiac TnT levels: *0.11 +/- 0.09 ng/mL; *p < 0.05). Also, tissue oxygenation (tpO2; mm Hg) was significantly improved during reperfusion in FX06-treated pigs when compared with controls (liver 51 +/- 4 vs. *65 +/- 4; serosa 44 +/- 5 vs. *55 +/- 7; mucosa 14 +/- 4 vs. *26 +/- 4). Finally, FX06 reduced accumulation of myeloperoxidase-positive cells (mainly neutrophils) in myocardium, liver, and small intestine and reduced interleukin-6 plasma levels (*p < 0.05; compared with controls)., Conclusion: We conclude that in a pig model of HS and reperfusion, administration of FX06 during reperfusion protects shock- susceptible organs such as heart, lung, liver, and small intestine.
- Published
- 2009
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45. Extracorporeal cell therapy with granulocytes in a pig model of Gram-positive sepsis.
- Author
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Sauer M, Altrichter J, Kreutzer HJ, Lögters T, Scholz M, Nöldge-Schomburg G, Schmidt R, and Mitzner SR
- Subjects
- Animals, Female, Gram-Positive Bacterial Infections microbiology, HL-60 Cells, Humans, Plasmapheresis methods, Prospective Studies, Sepsis blood, Staphylococcus aureus isolation & purification, Survival Analysis, Swine, Disease Models, Animal, Gram-Positive Bacterial Infections therapy, Granulocytes transplantation, Renal Dialysis methods, Sepsis therapy
- Abstract
Objectives: Granulocyte transfusions have been used to treat immune cell dysfunction in sepsis. As granulocyte transfusions can trigger tissue injury via local effects of neutrophils, we hypothesized that extracorporeal treatment of plasma using granulocytes would prove beneficial while having less side effects., Design: Prospective controlled three-armed animal study., Setting: Research laboratory., Subjects: Twenty-one female immature pigs (7.5-12 kg, 7-9 weeks old)., Interventions: Three groups of spontaneously breathing, sedated pigs (n = 7 each) received an intravenous lethal dose of live Staphylococcus aureus over 1 hour. Although group I had no specific treatment (control), group II and III were subsequently treated for 4 hours with an extracorporeal device containing either no cells (sham control, group II) or human cell line-derived granulocytic cells (group III). Survival time and physiologic, biochemical, and hematologic parameters were monitored for 7 days., Measurements and Main Results: All animals of group I died during the observation time (mean survival time: 70 hours). In group II, two of seven and in group III, six of seven animals survived the observation time (mean survival: 75 and 168 hours, respectively). Survival differences were significant between group I and III (p < 0.001) and between group II and III (p < 0.05) but not between group I and II (p = 0.43). Furthermore, group differences in bacterial blood concentrations, differential blood count, blood gases, lactate, and interleukins were observed. The extracorporeal cell treatment was well tolerated by the animals., Conclusions: Extracorporeal therapy with granulocytic cells significantly improved survival in a pig model of sepsis. Further studies with this approach are encouraged.
- Published
- 2009
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46. Breath analysis in critically ill patients: potential and limitations.
- Author
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Schubert JK, Miekisch W, Geiger K, and Nöldge-Schomburg GF
- Subjects
- Cholesterol metabolism, Equipment Design, Graft Rejection, Humans, Hydrocarbons analysis, Hydrocarbons metabolism, Lipid Peroxidation, Liver Diseases metabolism, Models, Theoretical, Renal Insufficiency metabolism, Respiration, Artificial instrumentation, Volatilization, Biomarkers analysis, Breath Tests, Critical Illness
- Abstract
Breath tests are attractive since they are noninvasive and can be repeated frequently in the dynamically changing state of critically ill patients. Volatile organic compounds can be produced anywhere in the body and are transported via the bloodstream and exhaled through the lung. They can reflect physiologic or pathologic biochemical processes such as lipid peroxidation, liver disease, renal failure, allograft rejection, and dextrose or cholesterol metabolism. This review describes the diagnostic potential of endogenous organic volatile substances in the breath of critically ill patients. Since many of these patients require ventilatory support, aspects of breath analysis under mechanical ventilation will be addressed. Analytical procedures, problems concerning the physiologic meaning of breath markers and future developments will be discussed.
- Published
- 2004
- Full Text
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