In JoVE (1)

Other Publications (9)

Articles by Felix Erdfelder in JoVE

 JoVE Medicine

A Model to Simulate Clinically Relevant Hypoxia in Humans

1Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Bonn, 2Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn, 3Institute for Terrestrial and Aquatic Wildlife Research, University of Veterinary Medicine Hannover, 4Institute of Physiology 2, University of Bonn

JoVE 54933

Other articles by Felix Erdfelder on PubMed

The Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors Vatalanib and Pazopanib Potently Induce Apoptosis in Chronic Lymphocytic Leukemia Cells in Vitro and in Vivo

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. Jul, 2010  |  Pubmed ID: 20570929

There is evidence that vascular endothelial growth factor (VEGF) is a critical microenvironmental factor that exerts angiogenesis-independent effects on the survival of chronic lymphocytic leukemia (CLL) cells. Vatalanib and pazopanib are potent orally available VEGF receptor tyrosine kinase inhibitors. We investigated the efficacy and selectivity of both compounds in CLL cells, simulated potential combination with conventional cytostatics, and tested the effect of both substances on CLL-like tumor xenografts.

Flow Cytometry and Polymerase Chain Reaction-based Analyses of Minimal Residual Disease in Chronic Lymphocytic Leukemia

Advances in Hematology. 2010  |  Pubmed ID: 20886004

New therapeutic strategies developed recently for chronic lymphocytic leukemia (CLL) have led to remarkable treatment response rates and complete hematological remissions. This means highly sensitive and specific techniques are increasingly needed to evaluate minimal residual disease (MRD) in CLL patients. Quantitative MRD levels can be used as prognostic markers, where total MRD eradication is associated with prolonged survival. Nowadays, PCR and flow cytometry techniques used to detect MRD in CLL patients can generate reliable and quantitative results with the highest sensitivity. MRD Flow is based on four-color flow cytometry using specific antibody combinations. For allele specific oligonucleotide real-time quantification (ASO RQ) PCR individual primers are designed to detect a specific immunoglobulin heavy chain (IgH) rearrangement in each patient clone. Five comprehensive studies investigated and compared the sensitivity and specificity of both methods. Groups of patients receiving different therapies were analyzed at different time points to generate quantitative MRD levels and MRD kinetics. All studies confirmed that both methods generate equivalent results with regard to sensitivity and MRD quantification, although each method has advantages and disadvantages in the daily routine of a standard hematological laboratory. Here, we review these investigations and compare their results in the light of modern therapies.

High Lymphoid Enhancer-binding Factor-1 Expression is Associated with Disease Progression and Poor Prognosis in Chronic Lymphocytic Leukemia

Hematology Reports. Jan, 2010  |  Pubmed ID: 22184516

We determined lymphoid enhancer-binding factor-1 (LEF1) mRNA expression in 112 chronic lymphocytic leukemia (CLL) samples and assessed correlations with the prognostic markers ZAP70 and CD38, Binet stages, the percentage of lymphocytes in the peripheral blood, and fibromodulin (FMOD) transcripts. The mean LEF1 relative expression ratios (RER) were 53.72 and 37.10 in ZAP70-positive and ZAP70-negative patients, respectively (P=0.004). However, we did not observe a significant difference in LEF1 expression between CD38-positive and CD38-negative patients. Moreover, patients requiring treatment showed a mean LEF1 RER of 85.61 whereas patients in recently diagnosed Binet A stage had a mean of only 22.01 (P<0.001). We also found significant correlations of LEF1 with the percentage of lymphocytes and FMOD expression. Our results suggest that high LEF1 expression is associated with poor prognosis and disease progression. Thus, LEF1 might be involved in the process of disease progression and possibly can serve as a molecular parameter for risk assessment and/or monitoring of CLL.

CD44 in Hematological Neoplasias

Annals of Hematology. May, 2011  |  Pubmed ID: 21258793

The CD44 protein family spans a large group of transmembrane glycoproteins acquired by alternative splicing and post-translational modifications. The great heterogeneity in molecular structure is reflected in its various important functions: CD44 mediates (1) interaction between cell and extracellular matrix, (2) signal submission, e.g., by acting as co-receptor for membrane-spanning receptor tyrosine kinases or by association with intracellular molecules initiating several signaling pathways, and (3) anchor function connecting to the cytoskeleton via the ezrin-radixin-moesin protein family. The expression pattern of the different CD44 isoforms display strong variations dependent on cell type, state of activation, and differentiation stage. In hematopoietic cells, CD44 mediates interaction of progenitor cells and bone marrow stroma during hematopoiesis, regulates maturation, and activation-induced cell death in T cells, influences neutrophil and macrophage migration as well as cytokine production, and participates in lymphocyte extravasation and migration. CD44 is involved in development and progress of hematological neoplasias by enhancement of apoptotic resistance, invasiveness, as well as regulation of bone marrow homing, and mobilization of leukemia-initiating cells into the peripheral blood. Thereby altered CD44 expression functions as marker for worse prognosis in most hematological malignancies. Additionally, CD44 expression levels can be used to distinguish between different hematological neoplasias and subtypes. Concerning new treatment strategies, CD44 displays promising potential either by direct targeting of CD44 expressed on the malignant cells or reversing an acquired resistance to primary treatment mediated through altered CD44 expression. The former can be achieved by antibody or hyaluronan-based immunotherapy.

Use of the Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1) As a Diagnostic Tool in Chronic Lymphocytic Leukemia (CLL)

Leukemia Research. Oct, 2011  |  Pubmed ID: 21531460

Flow cytometry is commonly used to establish the diagnosis of chronic lymphocytic leukemia (CLL). A defined combination of antibodies discriminates between normal B cells and CLL cells (coexpression of CD5, CD19, and CD23). The receptor tyrosine-like orphan receptor one (ROR1) is an embryonic glycoprotein involved in several developmental processes. It was shown to be highly and specifically expressed on circulating B lymphoma cells, but not on normal B cells. Here, we examined the potential of ROR1 as a diagnostic marker in initial and follow-up diagnostics of patients with CLL. 105 untreated and 72 treated patients, as well as healthy volunteers were examined using flow cytometry assays. Furthermore, we examined 10 patients with various B cell non-Hodgkin lymphomas (B-NHL). ROR1 was detected using a directly labeled antibody. We detected uniformly high ROR1 expression levels in all CLL samples. In marked contrast, only low or absent ROR1 expression levels were found on B cells from healthy donors. ROR1 expression in CLL patients was not influenced by various treatments. Taken together, ROR1 may be used as a diagnostic marker for CLL. As it is the only antigen which can exclusively be detected on neoplastic B cells it may greatly increase both, specificity as well as sensitivity, in lymphoma diagnostics.

Monitoring of Cerebral Oxygen Saturation During Resuscitation in Out-of-hospital Cardiac Arrest: a Feasibility Study in a Physician Staffed Emergency Medical System

Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. Oct, 2014  |  Pubmed ID: 25286829

Despite recent advances in resuscitation algorithms, neurological injury after cardiac arrest due to cerebral ischemia and reperfusion is one of the reasons for poor neurological outcome. There is currently no adequate means of measuring cerebral perfusion during cardiac arrest. It was the aim of this study to investigate the feasibility of measuring near infrared spectroscopy (NIRS) as a potential surrogate parameter for cerebral perfusion in patients with out-of-hospital resuscitations in a physician-staffed emergency medical service.

Evaluation of Near-infrared Spectroscopy Under Apnea-dependent Hypoxia in Humans

Journal of Clinical Monitoring and Computing. Dec, 2015  |  Pubmed ID: 25649718

In this study we investigated the responsiveness of near-infrared spectroscopy (NIRS) recordings measuring regional cerebral tissue oxygenation (rSO2) during hypoxia in apneic divers. The goal was to mimic dynamic hypoxia as present during cardiopulmonary resuscitation, laryngospasm, airway obstruction, or the "cannot ventilate cannot intubate" situation. Ten experienced apneic divers performed maximal breath hold maneuvers under dry conditions. SpO2 was measured by Masimo™ pulse oximetry on the forefinger of the left hand. NIRS was measured by NONIN Medical's EQUANOX™ on the forehead or above the musculus quadriceps femoris. Following apnea median cerebral rSO2 and SpO2 values decreased significantly from 71 to 54 and from 100 to 65%, respectively. As soon as cerebral rSO2 and SpO2 values decreased monotonically the correlation between normalized cerebral rSO2 and SpO2 values was highly significant (Pearson correlation coefficient = 0.893). Prior to correlation analyses, the values were normalized by dividing them by the individual means of stable pre-apneic measurements. Cerebral rSO2 measured re-saturation after termination of apnea significantly earlier (10 s, SD = 3.6 s) compared to SpO2 monitoring (21 s, SD = 4.4 s) [t(9) = 7.703, p < 0.001, r(2) = 0.868]. Our data demonstrate that NIRS monitoring reliably measures dynamic changes in cerebral tissue oxygen saturation, and identifies successful re-saturation faster than SpO2. Measuring cerebral rSO2 may prove beneficial in case of respiratory emergencies and during pulseless situations where SpO2 monitoring is impossible.

Dynamic Prediction of the Need for Renal Replacement Therapy in Intensive Care Unit Patients Using a Simple and Robust Model

Journal of Clinical Monitoring and Computing. Dec, 2015  |  Pubmed ID: 26686690

We aimed at identifying a model that dynamically predicts future need for renal replacement therapy (RRT) in intensive care unit (ICU) patients and can easily be implemented for online monitoring at the bedside. 7290 interdisciplinary ICU admissions were investigated. Patients with <3 days of stay or RRT in the first 2 days were excluded. 1624 of the remaining 2625 patients had a normal serum creatinine at admission. Every second of these 1624 patients was used for model calibration whereas the other half and, in addition, the 1001 patients with elevated serum creatinine were exclusively used for validation. Discriminant analysis was used to determine and validate a combination of clinical parameters that predicts the need for RRT 72 h ahead. Based on the calibration sample, stepwise discriminant analysis selected the serum values of (1) current urea, (2) current lactate, (3) the ratio of current and admission serum creatinine, and (4) the mean urine output of the previous 24 h. In the validation datasets, the model reached areas under the receiver operating characteristic curve of 0.866 and 0.833 in patients with normal and elevated serum creatinine at admission, respectively. Moreover, the model's predictive value extended to at least 5 days prior to initiation of RRT and exceeded that of the RIFLE classification at all investigated prediction intervals. We identified a robust model that dynamically predicts the future need for RRT successfully. This tool may help improve timing of therapy and prognosis in ICU patients.

Nurse Staffing Calculation in the Emergency Department - Performance-Oriented Calculation Based on the Manchester Triage System at the University Hospital Bonn

PloS One. 2016  |  Pubmed ID: 27138492

To date, there are no valid statistics regarding the number of full time staff necessary for nursing care in emergency departments in Europe.

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