8 results on '"Klaus Tenbrock"'
Search Results
2. Time of Disease‐Modifying Antirheumatic Drug Start in Juvenile Idiopathic Arthritis and the Likelihood of a Drug‐Free Remission in Young Adulthood
- Author
-
Martina Niewerth, Johannes-Peter Haas, Ariane Klein, Gerd Horneff, Jens Klotsche, Peer Aries, Kirsten Minden, Eva Seipelt, Stefanie Tatsis, Ivan Foeldvari, Martin Aringer, Klaus Tenbrock, and Angela Zink
- Subjects
Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Remission, Spontaneous ,Arthritis ,03 medical and health sciences ,Juvenile Arthritis Disease Activity Score ,0302 clinical medicine ,Rheumatology ,Quality of life ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Young adult ,Disease-modifying antirheumatic drug ,Child ,Prospective cohort study ,030203 arthritis & rheumatology ,business.industry ,medicine.disease ,Arthroplasty ,Arthritis, Juvenile ,Treatment Outcome ,Antirheumatic Agents ,Female ,Methotrexate ,business ,Follow-Up Studies ,medicine.drug - Abstract
Objective To study juvenile idiopathic arthritis (JIA) long-term outcomes in relation to the time of initiation of biologic disease-modifying antirheumatic drug (bDMARD). Methods Outcomes of JIA patients prospectively followed by the Biologika in der Kinderrheumatologie (BiKeR) and Juvenile Arthritis Methotrexate/Biologics Long-Term Observation (JuMBO) registers were analyzed with regard to drug-free remission and inactive disease, functional status and quality of life, and surgery. To analyze the influence of early bDMARD therapy on outcomes, patients were assigned to 3 groups based on the time from symptom onset to bDMARD start (G1: ≤2 years, G2: >2 to ≤5 years, and G3: >5 years). Propensity score-adjusted outcome differences were analyzed by multinomial logistic regression analyses among the groups. Results A total of 701 JIA patients were observed for mean ± SD 9.1 ± 3.7 years. At the last follow-up (disease duration mean ± SD 14.3 ± 6.1 years), 11.7% of patients were in drug-free remission, and 40.0% had inactive disease. More than half of the patients reported no functional limitation, while 5% had undergone arthroplasty, and 3% had eye surgery. At the 10-year time point, patients in G1 (n = 108) were significantly more likely to be in drug-free remission than those patients who began treatment later (G2, n = 199; G3, n = 259), with 18.5%, 10.1%, and 4.9%, respectively. Patients in G1 had significantly lower disease activity (clinical Juvenile Arthritis Disease Activity Score in 10 joints = 4.9), a better overall well-being (18.2% patient global assessment score = 0), and higher functional status (59.2% Health Assessment Questionnaire score = 0), compared to patients in G3 (7.1, 8.4%, and 43.7%, respectively). G1 patients required arthroplasty significantly less frequently than G3 patients and had significantly lower disease activity over time than patients in both G2 and G3. Conclusion Early DMARD treatment is associated with better disease control and outcomes, which supports the concept of a "window of opportunity" for JIA.
- Published
- 2019
3. Flow-volume loops measured with electrical impedance tomography in pediatric patients with asthma
- Author
-
Steffen Leonhardt, Chuong Ngo, Klaus Tenbrock, Falk Dippel, and Sylvia Lehmann
- Subjects
Male ,Pulmonary and Respiratory Medicine ,Spirometry ,medicine.medical_specialty ,Adolescent ,medicine.drug_class ,medicine.medical_treatment ,0206 medical engineering ,02 engineering and technology ,Pulmonary function testing ,03 medical and health sciences ,FEV1/FVC ratio ,0302 clinical medicine ,Bronchodilator ,Internal medicine ,Electric Impedance ,medicine ,Humans ,Child ,Lung ,Tomography ,Electrical impedance tomography ,Asthma ,Mechanical ventilation ,medicine.diagnostic_test ,business.industry ,medicine.disease ,020601 biomedical engineering ,Respiratory Function Tests ,030228 respiratory system ,Pediatrics, Perinatology and Child Health ,Breathing ,Cardiology ,Female ,business - Abstract
Background Electrical impedance tomography (EIT) provides information on global and regional ventilation during tidal breathing and mechanical ventilation. During forced expiration maneuvers, the linearity of EIT and spirometric data has been documented in healthy persons. The present study investigates the potential diagnostic use of EIT in pediatric patients with asthma. Methods EIT and spirometry were performed in 58 children with asthma (average age ± SD: 11.86 ± 3.13 years), and 58 healthy controls (average age ± SD: 12.12 ± 2.9 years). The correlation between EIT data and simultaneously acquired spirometric data were tested for FEV1, FEV0.5 , MEF75 , MEF50 , and MEF25 . Binary classification tests were performed for the EIT-derived Tiffeneau index FEV1 /FVC and the bronchodilator test index ΔFEV1 . Average flow-volume (FV) loops were generated for patients with pathologic spirometry to demonstrate the feasibility of EIT for graphic diagnosis of asthma. Results Spirometry and global EIT-based FV loops showed a strong correlation (P 0.9 in FEV1 and FEV0.5 ). In all criteria, the binary classification tests yielded high specificity (>93%), a high positive predictive value (≥75%) and a high negative predictive value (>80%), while sensitivity was higher in ΔFEV1 (86.67%) and lower in FEV1 /FVC (25% and 35.29%). A typical concave shape of the EIT-derived average FV loops was observed for asthmatic children with improvement after bronchospasmolysis. Conclusions Global FV loops derived from EIT correlate well with spirometry. Positive bronchospasmolysis can be observed in EIT-derived FV loops. Flow-volume loops originated from EIT have a potential to visualize pulmonary function.
- Published
- 2018
4. Author response for 'Nrf2 expression driven by Foxp3 specific deletion of Keap1 results in loss of immune tolerance in mice'
- Author
-
Angela Schippers, Kim Ohl, Tobias Bopp, Christoph Jan Wruck, Patricia Klemm, Norbert Wagner, Klaus Tenbrock, Anandhi Rajendiran, and Athanassios Fragoulis
- Subjects
Expression (architecture) ,FOXP3 ,Biology ,KEAP1 ,Cell biology ,Immune tolerance - Published
- 2019
5. Electrical impedance tomography as possible guidance for individual positioning of patients with multiple lung injury
- Author
-
Chuong Ngo, Sylvia Lehmann, Konrad Heimann, Lukas Bergmann, Simone Schrading, Steffen Leonhardt, Klaus Tenbrock, and Norbert Wagner
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Lung ,Supine position ,Respiratory rate ,business.industry ,030208 emergency & critical care medicine ,Lung injury ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,030228 respiratory system ,medicine ,Breathing ,Immunology and Allergy ,Lung volumes ,Radiology ,business ,Electrical impedance tomography ,Genetics (clinical) ,Tidal volume - Abstract
Introduction Electrical Impedance Tomography (EIT) is a tomographic, radiation-free technique based on the injection of a harmless alternating current. Objective As electrical impedance strictly correlates with the variation of air content, EIT delivers highly dynamic information about global and regional ventilation. We want to demonstrate the potential of EIT individualizing ventilation by positioning. Methods Gravity-dependent EIT findings were analyzed retrospectively in a critically ill mechanically ventilated pediatric patient with cystic fibrosis and coincident lung diseases. To further evaluate gravity-dependent changes in ventilation, six adult healthy and spontaneously breathing volunteers were investigated during simultaneous detection of EIT, breathing patterns, tidal volume (VT) and breathing frequency (BF). Results EIT findings in healthy lungs in five positions showed gravity-dependent effects of ventilation with overall ventilation of predominantly the right lung (except during left-side positioning) and with the ventral lung in supine, prone and upright position. These EIT-derived observations are in line with pathophysiological mechanisms and earlier EIT studies. Unexpectedly, the patient with cystic fibrosis and lobectomy of the right upper and middle lobe one year earlier, showed improvement of global and regional ventilation in the right position despite reduced lung volume and overinflation of this side. This resulted in individualized positioning and improvement of ventilation. Conclusions Although therapeutic recommendations are available for gravitational influences of lung ventilation, they can be contradictory depending on the underlying lung disease. EIT has the potential to guide therapists in the positioning of patients according to their individual condition and disease, especially in case of multiple lung injury.
- Published
- 2016
6. Efficacy and Safety of Etanercept in Patients With the Enthesitis-Related Arthritis Category of Juvenile Idiopathic Arthritis: Results From a Phase III Randomized, Double-Blind Study
- Author
-
Klaus Tenbrock, Kirsten Minden, Gerd Horneff, Gerd Ganser, Hans-Iko Huppertz, Ivan Foeldvari, Jasmin Kümmerle-Deschner, and Ralf Trauzeddel
- Subjects
musculoskeletal diseases ,medicine.medical_specialty ,Ankylosing spondylitis ,business.industry ,Immunology ,Arthritis ,Placebo ,medicine.disease ,Rheumatology ,Etanercept ,Surgery ,Juvenile Arthritis Disease Activity Score ,Internal medicine ,medicine ,Clinical endpoint ,Back pain ,Immunology and Allergy ,medicine.symptom ,skin and connective tissue diseases ,business ,medicine.drug - Abstract
Objective To evaluate the efficacy and safety of etanercept in patients with enthesitis-related arthritis (ERA) in juvenile idiopathic arthritis (JIA). Methods This was a 2-phase study in JIA patients with active, refractory ERA. Phase I was an open-label, uncontrolled 24-week study period in which all patients were administered etanercept. Patients considered to be treatment responders at week 24 according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) criteria for improvement in juvenile arthritis entered the second phase, a 24-week randomized, double-blind, placebo-controlled withdrawal study, for an additional 24 weeks, for evaluation of the primary end point, occurrence of a disease flare from week 24 to week 48, based on the ACR preliminary definition of disease flare in juvenile arthritis. Results Forty-one patients were enrolled. At week 24, treatment with etanercept resulted in response rates of 93%, 93%, 80%, 56%, and 54% based on the ACR Pedi 30, Pedi 50, Pedi 70, Pedi 90, and Pedi 100 criteria, respectively. In addition, a marked decrease in all disease activity measures was observed. The mean number of tender joints, swollen joints, and joints with active arthritis decreased by 91%, 97%, and 94%, respectively. Physician's global assessment of disease activity, parent's assessment of patient's overall well-being, and the Childhood Health Assessment Questionnaire disability index improved by 91%, 80%, and 86%, respectively. The number of tender enthesis sites and total scores for back pain, nocturnal pain, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, and Juvenile Arthritis Disease Activity Score based on 10-joint counts (JADAS10) decreased by 75%, 72%, 81%, 72%, 85%, and 87%, respectively. In phase II, 38 patients were randomly assigned to receive placebo (n = 18) or to continue receiving etanercept (n = 20). Up to week 48, 12 disease flares occurred, in 9 patients receiving placebo and 3 patients receiving etanercept (odds ratio 6.0, P = 0.02). There were no serious infections, malignancies, or deaths. Conclusion In this study of patients with the ERA category of JIA, etanercept proved effective, as indicated by high ACR Pedi response rates and JADAS10 response rates at week 24. Patients who continued treatment with etanercept had significantly fewer flares than those who received placebo, although 50% of patients in the placebo group did not experience a flare. Treatment suspension may be a consideration for patients with the ERA category of JIA who achieve remission.
- Published
- 2015
7. Regulatory T cells in systemic lupus erythematosus
- Author
-
Kim Ohl and Klaus Tenbrock
- Subjects
Autoimmune disease ,business.industry ,Immunology ,FOXP3 ,hemic and immune systems ,chemical and pharmacologic phenomena ,medicine.disease ,Treg cell ,Pathogenesis ,immune system diseases ,medicine ,Immunology and Allergy ,skin and connective tissue diseases ,business ,Ex vivo - Abstract
Systemic lupus erythematosus (SLE), an autoimmune disease, develops when immunologic self-tolerance fails. Treg cells are a subset of CD4(+) T cells that maintain self-tolerance by suppressing autoreactive lymphocytes. Defects in Treg cells are therefore considered to be an aspect of SLE pathogenesis. Nevertheless, reports on the numbers and function of Treg cells in SLE are contradictory and the definitive role of Treg cells in SLE remains unclear. In this review, we summarize findings from murine models and ex vivo experiments, which provide insights into the mechanisms that result in the breakdown of tolerance. We also include recent findings about Treg-cell subsets and their markers in human SLE. The identification of unique markers to identify bona fide Treg cells, as well as therapies to reconstitute the balance between Treg cells and autoreactive T cells in SLE, are the future challenges for SLE research.
- Published
- 2014
8. The p38-Mediated Rapid Down-Regulation of Cell Surface gp130 Expression Impairs Interleukin-6 Signaling in the Synovial Fluid of Juvenile Idiopathic Arthritis Patients
- Author
-
Nora Honke, Jeff Bierwagen, Kim Ohl, Rainer Fischer, Joachim Peitz, Stefano Di Fiore, Stefan Wüller, Norbert Wagner, Anastasia Wiener, and Klaus Tenbrock
- Subjects
medicine.diagnostic_test ,biology ,business.industry ,Immunology ,Cell ,Arthritis ,medicine.disease ,Flow cytometry ,Cell biology ,Proinflammatory cytokine ,medicine.anatomical_structure ,Rheumatology ,medicine ,biology.protein ,Immunology and Allergy ,Synovial fluid ,Signal transduction ,Receptor ,Interleukin 6 ,business - Abstract
Objective Interleukin-6 (IL-6) signaling plays an important proinflammatory role, but this role is restricted by regulatory mechanisms that, for example, reduce the cell surface availability of the signal-transducing chain of the IL-6 receptor, gp130. The aim of this study was to determine whether the inflammatory environment in arthritic joints has an impact on monocytic gp130 surface expression and the extent to which regulatory processes in the synovial fluid (SF) can be reproduced in an in vitro model. Methods Flow cytometry and live cell imaging were used to measure the cell surface expression and internalization of gp130. STAT-3 phosphorylation was monitored by flow cytometry and Western blotting. Results In patients with juvenile idiopathic arthritis (JIA), levels of cell surface gp130 expression in SF monocytes were reduced compared to those in peripheral blood (PB) monocytes. These reduced levels were reproduced when PB monocytes from healthy donors were stimulated with SF, and this reduction was dependent on p38 MAPK. The induction of p38 by IL-1β in PB monocytes interfered with IL-6 signaling due to the reduced cell surface expression of gp130. Conclusion These results suggest that p38-mediated proinflammatory stimuli induce the down-regulation of gp130 on monocytes and thus restrict gp130-mediated signal transduction. This regulatory mechanism could be of relevance to processes in the inflamed joints of patients with JIA.
- Published
- 2014
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.