Claudius Thomé

RWTH Aachen University, Aachen, North Rhine-Westphalia, Germany

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Publications (95)241.28 Total impact

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    ABSTRACT: Spontaneous intracerebral hemorrhage (ICH) is associated with high morbidity and mortality. Cortical spreading depolarizations (CSDs) increase brain matrix metalloproteinase (MMP)-9 activity leading to perihematomal edema expansion in experimental ICH.
    Neurocritical Care 08/2014; · 3.04 Impact Factor
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    ABSTRACT: Background Three-dimensional (3D) culture in porous biomaterials as well as stimulation with growth factors are known to be supportive for intervertebral disc cell differentiation and tissue formation. Unless sophisticated releasing systems are used, however, effective concentrations of growth factors are maintained only for a very limited amount of time in in vivo applications. Therefore, we investigated, if an initial boost with transforming growth factor-beta 1 (TGF-beta 1) is capable to induce a lasting effect of superior cartilaginous differentiation in slightly and severely degenerated human annulus fibrosus (AF) cells.Methods Human AF tissue was harvested during surgical treatment of six adult patients with lumbar spinal diseases. Grading of disc degeneration was performed with magnet resonance imaging. AF cells were isolated and expanded in monolayer culture and rearranged three-dimensionally in a porous biomaterial consisting of stepwise absorbable poly-glycolic acid and poly-(lactic-co-glycolic) acid and a supportive fine net of non-absorbable polyvinylidene fluoride. An initial boost of TGF-beta 1 or TGF-beta 1 and hyaluronan was applied and compared with controls. Matrix formation was assessed at days 7 and 21 by (1) histological staining of the typical extracellular matrix molecules proteoglycan and type I and type II collagens and by (2) real-time gene expression analysis of aggrecan, decorin, biglycan, type I, II, III, and X collagens as well as of catabolic matrix metalloproteinases MMP-2 and MMP-13.ResultsAn initial boost with TGF-beta 1 or TGF-beta 1 and hyaluronan did not enhance the expression of characteristic AF matrix molecules in our 3D culture system. AF cells showed high viability in the progressively degrading biomaterial. Stratification by grade of intervertebral disc degeneration showed that AF cells from both, slightly degenerated, or severely degenerated tissue are capable of significant up-regulations of characteristic matrix molecules in 3D culture. AF cells from severely degenerated tissue, however, displayed significantly lower up-regulations in some matrix molecules such as aggrecan.Conclusions We failed to show a supportive effect of an initial boost with TGF-beta 1 in our 3D culture system. This underlines the need for further investigations on growth factor releasing systems.
    Journal of Orthopaedic Surgery and Research 08/2014; 9(1):73. · 1.01 Impact Factor
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    ABSTRACT: Elevated brain potassium ([K+]) levels are associated with neuronal damage in experimental models. The role of brain extracellular [K+] in patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) and its association with hemorrhage load, metabolic dysfunction and outcome has not been studied so far.
    Critical care (London, England) 06/2014; 18(3):R119. · 4.72 Impact Factor
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    ABSTRACT: Recent evidence suggests axonal injury after aneurysmal subarachnoid haemorrhage (aSAH). The microtubule-associated protein, tau, has been shown to be elevated in the cerebrospinal fluid after aSAH, however, brain extracellular tau levels and their relation to long-term neurological and cognitive outcomes have not been investigated. Serial cerebral microdialysis (CMD) samples were collected from 22 consecutive aSAH patients with multimodal neuromonitoring to determine CMD-total-tau by ELISA. CMD-total-tau was analysed considering other brain metabolic parameters, brain tissue oxygen tension (PbtO2), and functional and neuropsychological outcome at 12 months. All outcome models were analysed using generalised estimating equations with an autoregressive working correlation matrix to account for multiple measurements of brain extracellular proteins per subject. CMD-total-tau levels positively correlated with brain extracellular fluid levels of lactate (r=0.40, p<0.001), glutamate (r=0.45, p<0.001), pyruvate (r=0.26, p<0.001), and the lactate-pyruvate ratio (r=0.26, p<0.001), and were higher in episodes of hypoxic (PbtO2<20 mm Hg) brain extracellular lactate elevation (>4 mmol/L) (p<0.01). More importantly, high CMD-total-tau levels were associated with poor functional outcome (modified Rankin Scale ≥4) 12 months after aSAH even after adjusting for disease severity and age (p=0.001). A similar association was found with 3/5 neuropsychological tests indicative of impairments in cognition, psychomotor speed, visual conceptualisation and frontal executive functions at 1 year after aSAH (p<0.01). These results suggest that CMD-total tau may be an important biomarker for predicting long-term outcome in patients with severe aSAH. The value of axonal injury needs further confirmation in a larger patient cohort, preferably combined with advanced imaging techniques.
    Journal of neurology, neurosurgery, and psychiatry 04/2014; · 4.87 Impact Factor
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    ABSTRACT: Degenerative disc disease (DDD) of the cervical spine is common after middle age and can cause loss of disc height with painful nerve impingement, bone and joint inflammation. Despite the clinical importance of these problems, in current publications the pathology of cervical disc degeneration has been studied merely from a morphologic view point using magnetic resonance imaging (MRI), without addressing the issue of biological treatment approaches. So far a wide range of endogenously expressed bioactive factors in degenerative cervical disc cells has not yet been investigated, despite its importance for gene therapeutic approaches. Although degenerative lumbar disc cells have been targeted by different biological treatment approaches, the quantities of disc cells and the concentrations of gene therapeutic factors used in animal models differ extremely. These indicate lack of experimentally acquired data regarding disc cell proliferation and levels of target proteins. Therefore, we analysed proliferation and endogenous expression levels of anabolic, catabolic, ant-catabolic, inflammatory cytokines and matrix proteins of degenerative cervical disc cells in three-dimensional cultures. Preoperative MRI grading of cervical discs was used, then grade III and IV nucleus pulposus (NP) tissues were isolated from 15 patients, operated due to cervical disc herniation. NP cells were cultured for four weeks with low-glucose in collagen I scaffold. Their proliferation rates were analysed using 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide. Their protein expression levels of 28 therapeutic targets were analysed using enzyme-linked immunosorbent assay. During progressive grades of degeneration NP cell proliferation rates were similar. Significantly decreased aggrecan and collagen II expressions (P<0.0001) were accompanied by accumulations of selective catabolic and inflammatory cytokines (disintegrin and metalloproteinase with thrombospondin motifs 4 and 5, matrix metalloproteinase 3, interleukin-1β, interleukin-1 receptor) combined with low expression of anti-catabolic factor (metalloproteinase inhibitor 3) (P<0.0001). This study might contribute to inhibit inflammatory catabolism of cervical discs.
    PLoS ONE 01/2014; 9(5):e96870. · 3.73 Impact Factor
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    ABSTRACT: Annulus fibrosus repair techniques for the intervertebral disc (IVD) address the unsolved problem of reherniation after IVD herniation and might facilitate the development of nucleus pulposus replacement techniques for IVD diseases. This study investigates the suitability of a bio-integrative annulus implant.Standardized box defects were applied to the annulus L3/4 and L4/5 of 16 sheep, followed by randomized insertion of the textile polyglycolic acid/polyvinylidene fluoride annulus implant in one of the defects. Explantation was conducted after 2, 6 and 12 weeks, followed by provocative pressure testing and histological analysis. At 2 weeks' follow-up, all specimens of the control defect group demonstrated uncontained herniated nucleus pulposus tissue in the annulus defects. For the treated specimens, the annulus implant consistently provided an effective barrier for herniating nucleus pulposus tissue, with no implant dislocation at all time-points. After 2 weeks, a homogeneous cell infiltration of the annulus implant was observed, leading to a progressive directional matrix build-up. Repair tissue thickness was significantly stronger with the annulus implant at all follow-ups (p < 0.01). No pronounced foreign body reaction and no difference in the amount of supra-annular scar tissue over the defect sites were observed. The implantation procedure inflicted annulus damage adjacent to the defect. At later time-points, however, no difference in comparison with the control defect group was evident. The investigated biointegrative annulus implant showed promising results with regard to biointegration, enhancement of repair tissue and function as a mechanical barrier in an ovine model. © 2013 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons, Ltd.
    Journal of Tissue Engineering and Regenerative Medicine 11/2013; · 4.43 Impact Factor
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    ABSTRACT: Moyamoya disease (MMD) is characterized by unique angiographic features of collateralization. However, a detailed quantification as well as comparative analysis with cerebrovascular atherosclerotic disease (CAD) and healthy controls have not been performed to date. We reviewed 67 patients with MMD undergoing Xenon-enhanced computed tomography, as well as 108 patients with CAD and 5 controls. In addition to cortical, central, and infratentorial regions of interest, particular emphasis was put on regions that are typically involved in MMD (pericallosal territory, basal ganglia). Cerebral blood flow (CBF), cerebrovascular reserve capacity (CVRC), and hemodynamic stress distribution were calculated. MMD is characterized by a significant, ubiquitous decrease in CVRC and a cortical but not pericallosal decrease in CBF when compared with controls. Baseline perfusion is maintained within the basal ganglia, and hemodynamic stress distribution confirmed a relative preservation of central regions of interest in MMD, indicative for its characteristic proximal collateralization pattern. In MMD and CAD, cortical and central CBF decreased significantly with age, whereas CVRC and hemodynamic stress distribution are relatively unaffected by age. No difference in CVRC of comparable regions of interest was seen between MMD and CAD, but stress distribution was significantly higher in MMD, illustrating the functionality of the characteristic rete mirabilis. Our data provide quantitative support for a territory-specific perfusion pattern that is unique for MMD, including central preservation of CBF compared with controls and patients with CAD. This correlates well with its characteristic feature of proximal collateralization. CVRC and hemodynamic stress distribution seem to be more robust parameters than CBF alone for assessment of disease severity.
    Stroke 11/2013; · 6.16 Impact Factor
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    ABSTRACT: Study Design. prospective cohort studyObjective. to determine the value of routine postoperative MR imaging early after lumbar decompression in patients with non-specific symptoms.Summary of background data. Imaging after lumbar surgery may be performed more readily even with non-specific symptoms and without neurological deficit.Methods. Patients undergoing elective lumbar decompression surgery completed standardized questionnaires, were assessed neurologically on admission, and underwent MRI scanning within 72h after surgery. Residual stenosis was graded as absent or mild (outcome A) or moderate to severe (outcome B). Surgical technique and intraoperative complications and postoperative neurological status were recorded.Results. We recruited 28 consecutive patients who reported significant improvement of preoperative symptoms. In 2/3 of all patients, postoperative imaging showed at least one segment with moderate or severe residual stenosis (B). Radiological outcome did not correlate with postoperative pain. Patient satisfaction index was comparable in group A and B. The cross section of the spinal canal was significantly wider with a drain in situ. This did not, however, translate into a difference in overall VAS or wound discomfort. Patients tended to report more back and leg pain with drains and were less satisfied with the result of the operation.Conclusions. Early postoperative MR imaging in patients with non-specific symptoms frequently shows radiologically relevant stenosis, which is neither associated with outcome nor patient satisfaction. Drain placement is associated with less radiological narrowing, but with lower patient satisfaction. Imaging without clinical correlate may yield non-discriminatory information likely to unsettle and puzzle both patient and health care provider.
    Spine 09/2013; 38(20):E1263-8. · 2.16 Impact Factor
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    ABSTRACT: Cerebral revascularization procedures are a treatment option in Moyamoya disease patients, but recent studies failed to show an immediate benefit in cerebrovascular atherosclerotic disease. To facilitate optimal efficacy of the procedure, a detailed characterization of a representative perioperative complication rate and the role of potential risk factors such as underlying pathology, antiplatelet therapy and the type of surgery performed is warranted and the purpose of this study. We included 158 consecutive patients with Moyamoya disease or cerebrovascular atherosclerotic disease undergoing 168 direct revascularization procedures. Type of disease, antiplatelet therapy, coagulation disorders, surgical technique, intraoperative complications, postoperative imaging, the need for revision and outcome at time of discharge were analyzed. Complication rate was low with a high patency rate of 97%. Six hemispheres (3.6%) needed to undergo surgical revision, early morbidity was 10.7% with no mortality, with evidence of ischemia in 6.9% of patients. Type of pathology treated and surgical technique did not influence outcome. Antiplatelet treatment was not associated with an increased risk for hemorrhage or revision, but improved outcome (p<0.05). Ischemia, hemorrhage and the need for revision aggravated outcome at time of discharge. EC-IC bypass surgery remains a treatment option in patients with Moyamoya disease, while its use in the context of atherosclerotic disease was recently put into question. Regardless, a detailed characterization of perioperative risk factors is needed to optimize a potential longterm benefit of surgery. At a high-volume center, the complication rate is low independent from the underlying pathology with a high patency rate. Antiplatelet treatment does not increase the risk of hemorrhagic complications, but may improve outcome. Longer follow-up is required to adequately assess the true efficacy of revascularization on stroke prevention.
    World Neurosurgery 07/2013; · 1.77 Impact Factor
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    ABSTRACT: INTRODUCTION: Diclofenac, a nonsteroidal anti-inflammatory drug, is commonly used as antipyretic therapy in intensive care. The purpose of this study was to investigate the effects of parenteral diclofenac infusion on brain homeostasis including brain tissue oxygen tension (PbtO2) and brain metabolism after aneurismal subarachnoid hemorrhage (aSAH). METHODS: We conducted a prospective, observational study with retrospective analysis of 21 consecutive aSAH patients with multimodal neuromonitoring. Cerebral perfusion pressure (CPP), mean arterial pressure (MAP), intracranial pressure (ICP), body temperature and PbtO2 were analyzed after parenteral diclofenac infusion administered over 34 minutes (20-45 IQR). Data are given as mean+/-standard error of mean and median with interquartile range (IQR) as appropriate. Time-series data were analyzed using a general linear model extended by generalized estimation equations (GEE). RESULTS: One-hundred-twenty-three interventions were analyzed. Body temperature decreased from 38.3+/-0.05degreesC by 0.8+/-0.06degreesC (P<0.001). A 10% decrease in MAP and CPP (P<0.001) necessitated an increase of vasopressors in 26% (N=32), colloids in 33% (N=41) and cristalloids in 5% (N=7) of interventions. PbtO2 decreased by 13% from a baseline value of 28.1+/-2.2mmHg, resulting in brain tissue hypoxia (PbtO2<20mmHg) in 38% (N=8) of patients and 35% (N=43) of interventions. PbtO2 < 30mmHg before intervention was associated with brain tissue hypoxia after parenteral diclofenac infusion (Likelihood ratio 40; AUC 93%; 95% CI 87-99%; P<0.001). Cerebral metabolism showed no significant changes after parenteral diclofenac infusion. CONCLUSIONS: Parenteral diclofenac infusion after aSAH effectively reduces body temperature, but may lead to CPP decrease and brain tissue hypoxia, which were both associated with poor outcome after aSAH.
    Critical care (London, England) 05/2013; 17(3):R88. · 4.72 Impact Factor
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    ABSTRACT: Painful degenerative disc diseases have been targeted by different biological treatment approaches. Nucleus pulposus (NP) cells play a central role in intervertebral disc (IVD) maintenance by orchestrating catabolic, anabolic and inflammatory factors that affect the extracellular matrix. IVD degeneration is associated with imbalances of these factors, resulting in a catabolic inflammatory metabolism. Therefore, accurate knowledge about their quantity and quality with regard to matrix synthesis is vital for a rational gene therapeutic approach. NP cells were isolated from 63 patients operated due to lumbar disc herniation (mean age 56 / range 29 - 84 years). Then, three-dimensional culture with low-glucose was completed in a collagen type I scaffold for four weeks. Subsequently cell proliferation evaluation was performed using 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide and intracellular concentration of 28 endogenously expressed anabolic, catabolic, inflammatory factors and relevant matrix proteins was determined by enzyme-linked immunosorbent assay. Specimen-related grades of degeneration were confirmed by preoperative magnetic resonance imaging. Independent from gender, age and grade of degeneration proliferation rates remained similar in all groups of NP cells. Progressive grades of degeneration, however, showed a significant influence on accumulation of selective groups of factors such as disintegrin and metalloproteinase with thrombospondin motifs 4 and 5, matrix metalloproteinase 3, metalloproteinase inhibitor 1 and 2, interleukin-1β and interleukin-1 receptor. Along with these changes, the key NP matrix proteins aggrecan and collagen II decreased significantly. The concentration of anabolic factors bone morphogenetic proteins 2, 4, 6 and 7, insulin-like growth factor 1, transforming growth factor beta 1 and 3, however, remained below the minimal detectable quantities. These findings indicate that progressive degenerative changes in NP may be problematic with regard to biologic treatment strategies. Hence, gene therapeutic interventions regulating relevant bioactive factors identified in this work might contribute to the development of regenerative treatment approaches for degenerative disc diseases.
    PLoS ONE 01/2013; 8(11):e81467. · 3.73 Impact Factor
  • Seizure 12/2012; · 2.00 Impact Factor
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    ABSTRACT: Regardless of current multimodal treatment strategies, the prognosis of patients harboring glioblastoma multiforme (GBM) is still dismal. The introduction of concomitant radiochemotherapy and adjuvant cyclic temozolomide has significantly improved the overall survival, compared to postoperative radiotherapy-alone. Furthermore this regimen shows a lower toxicity profile compared to previous nitrosourea-based chemotherapy and can easily be applied on an outpatient basis, thus potentially facilitating chemotherapy in rural and more remote areas. The distance to the oncological center has been shown to be a negative prognostic parameter in other types of cancer. Therefore, we aimed to investigate whether the introduction of temozolomide as the standard regimen in the treatment of GBM has influenced the administration of chemotherapy and the prognosis of patients depending on the distance to our neurooncological center. A total of 208 patients diagnosed with GBM (M:F=1.4:1), surgically resected between 1990 and 2009, thus covering the pre-temozolomide and the temozolomide-era, were included retrospectively in this analysis. The distance from the patients' residences to the neurooncological center was determined and statistical analysis was performed to assess its influence on overall survival and administration of adjuvant treatment (radiotherapy-only, nitrosourea-based chemotherapy and adjuvant temozolomide). Overall, 41.3% of the cohort underwent subtotal surgical resection, whereas a gross total resection was accomplished in 57.2%. The median distance to the neurooncological center was 75 km (range=1-870 km). Postoperatively, 68 patients (32.7%) received concomitant and adjuvant radiochemotherapy with temozolomide, 31 (14.9%) were treated with nitrosourea other than the Procarbazin, Lomustin, Vincristin (PCV), 34 (16.3%) with PCV, and 71 patients (34.1%) had radiotherapy-alone. The distance to the neurooncological center had a significant influence on overall survival for the whole cohort (p=0.027) and patients with increasing distances, were significantly less often treated with chemotherapy (p=0.05). With the introduction of temozolomide this relation was lost (overall survival, temozolomide and other agents: p=0.685/p=0.007; administration of adjuvant chemotherapy in the temozolomide-era/whole cohort: p=0.612/p=0.05). The distance to the neurooncological center negatively-influenced the prognosis of patients with GBM. Patients were less often treated with adjuvant chemotherapy in the pre-temozolomide era with increasing distance to the neurooncological center. Although the introduction of temozolomide as the standard chemotherapeutic agent in GBM treatment changed this fact, the influence of the distance to the specialized center should be kept in mind as a prognostic factor for this disease.
    Anticancer research 12/2012; 32(12):5515-9. · 1.71 Impact Factor
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    ABSTRACT: BACKGROUND: Regardless of current multimodal treatment strategies, the prognosis of patients harboring glioblastoma multiforme (GBM) is still dismal. The introduction of concomitant radiochemotherapy and adjuvant cyclic temozolomide has significantly improved the overall survival, compared to postoperative radiotherapy-alone. Furthermore this regimen shows a lower toxicity profile compared to previous nitrosourea-based chemotherapy and can easily be applied on an outpatient basis, thus potentially facilitating chemotherapy in rural and more remote areas. The distance to the oncological center has been shown to be a negative prognostic parameter in other types of cancer. Therefore, we aimed to investigate whether the introduction of temozolomide as the standard regimen in the treatment of GBM has influenced the administration of chemotherapy and the prognosis of patients depending on the distance to our neurooncological center. PATIENTS AND METHODS: A total of 208 patients diagnosed with GBM (M:F=1.4:1), surgically resected between 1990 and 2009, thus covering the pre-temozolomide and the temozolomide-era, were included retrospectively in this analysis. The distance from the patients' residences to the neurooncological center was determined and statistical analysis was performed to assess its influence on overall survival and administration of adjuvant treatment (radiotherapy-only, nitrosourea-based chemotherapy and adjuvant temozolomide). RESULTS: Overall, 41.3% of the cohort underwent subtotal surgical resection, whereas a gross total resection was accomplished in 57.2%. The median distance to the neurooncological center was 75 km (range=1-870 km). Postoperatively, 68 patients (32.7%) received concomitant and adjuvant radiochemotherapy with temozolomide, 31 (14.9%) were treated with nitrosourea other than the Procarbazin, Lomustin, Vincristin (PCV), 34 (16.3%) with PCV, and 71 patients (34.1%) had radiotherapy-alone. The distance to the neurooncological center had a significant influence on overall survival for the whole cohort (p=0.027) and patients with increasing distances, were significantly less often treated with chemotherapy (p=0.05). With the introduction of temozolomide this relation was lost (overall survival, temozolomide and other agents: p=0.685/p=0.007; administration of adjuvant chemotherapy in the temozolomide-era/whole cohort: p=0.612/p=0.05). CONCLUSION: The distance to the neurooncological center negatively-influenced the prognosis of patients with GBM. Patients were less often treated with adjuvant chemotherapy in the pre-temozolomide era with increasing distance to the neurooncological center. Although the introduction of temozolomide as the standard chemotherapeutic agent in GBM treatment changed this fact, the influence of the distance to the specialized center should be kept in mind as a prognostic factor for this disease.
    Anticancer research 12/2012; 32(12):5515-9. · 1.71 Impact Factor
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    ABSTRACT: Closure and biological repair of anulus fibrosus (AF) defects in intervertebral disc diseases is a therapeutic challenge. The aim of our study was to evaluate the anabolic properties of bioactive factors on cartilaginous matrix formation by AF cells. Human AF cells were harvested from degenerated lumbar AF tissue and expanded in monolayer culture. AF cell differentiation and matrix formation was initiated by forming pellet cultures and stimulation with hyaluronic acid (HA), human serum (HS), fibroblast growth factor-2 (FGF-2), transforming growth factor-β3 (TGF-β3) and TGF-β3/FGF-2 for up to 4 weeks. Matrix formation was assessed histologically by staining of proteoglycan, type I and type II collagens and by gene expression analysis of typical extracellular matrix molecules and of catabolic matrix metalloproteinases MMP-2 and MMP-13. AF cells, stimulated with HS, FGF-2 and most pronounced with TGF-β3 or TGF-β3/FGF-2 formed a cartilaginous matrix with significantly enhanced expression of matrix molecules and of MMP-13. Stimulation of AF cells with TGF-β3 was accompanied by induction of type X collagen, known to occur in hypertrophic cartilage cells having mineralizing potential. HA did not show any chondro-inductive characteristics. These findings suggest human serum, FGF-2 and TGF-β3 as possible candidates to support biological treatment strategies of AF defects.
    Tissue and Cell 10/2012; · 1.04 Impact Factor
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    ABSTRACT: Intervertebral disc (IVD) degeneration has been described as an aberrant, cell-mediated, age- and genetics-dependent molecular degeneration process, which can be accelerated by nutritional, mechanical and toxic factors. Collective involvement of these factors can result in structural failures, which are often associated with pain. Current treatment approaches are restricted to symptomatic therapies, not addressing options of restoring structural or biological deterioration of the IVD as the underlying problem. Therapeutic potentials of IVD cell transplantation, biomaterials, inhibiting or activating bioactive factors, including gene-therapeutic approaches, have been shown in vitro or in small animal models. Since human degenerative IVD cells display distinctive features with regard to cell biology and regenerative potential, we attempted a systematic review, investigating the in vitro response of human nucleus pulposus cells to different stimuli. Therefore, we conducted an electronic database search on Medline through July 2011 to identify, compare and discuss publications concerning the effects of cell-cell stimulation, bioactive factors, biomaterials and combinations thereof in terms of cell isolation, proliferation, differentiation and matrix protein synthesis. This survey and discussion might serve as a source for designing future biological treatment strategies for the human IVD. Copyright © 2012 John Wiley & Sons, Ltd.
    Journal of Tissue Engineering and Regenerative Medicine 08/2012; · 4.43 Impact Factor
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    ABSTRACT: BACKGROUND:: Acute neurological deficits after SAH correlate with outcome, and a phase of acute hypoperfusion has been characterized recently. ICG videography is an established intraoperative imaging technique with important descriptive potential. OBJECTIVE:: To analyze whether ICG can be used to analyze and confirm perfusion changes early after SAH. METHODS:: We prospectively enrolled 11 patients with acute SAH within the last 24hrs and 14 patients undergoing surgery for unruptured aneurysms. Cortical ICG videography was performed, and offline analysis included the arterial, parenchymal, and venous cortical compartment. Transit times, signal gradient, maximum of fluorescence intensity, as well as the area under the curve were calculated as surrogate markers for perfusion characteristics. RESULTS:: Arterial, parenchymal, and venous transit times were comparable in both groups. Velocity of signal change in SAH patients was significantly lower in all three compartments (p<0.001, p<0.01, p<0.001 resp.), as was the peak fluorescence intensity (p<0.001). In SAH patients, fluorescence intensity did not vary between areas with and without diffuse cortical blood. Area under the curve analysis showed significantly lower values in SAH patients compared to the control group (p<0.001). CONCLUSION:: Cortical ICG videography and analysis is feasible during surgery. Patients early after SAH feature a significantly lower velocity of signal change, lower peak of fluorescence intensity, and lower overall area under the curve, but similar transit times. This technique can be used to quantify perfusion alteration, in this case acute SAH, and may be used as an adapted measurement tool for intraoperative therapy.
    Neurosurgery 06/2012; · 2.53 Impact Factor
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    ABSTRACT: BACKGROUND: Vasospasm-related delayed cerebral ischemia (DCI) significantly impacts on outcome after aneurysmal subarachnoid hemorrhage (SAH). Erythropoietin (EPO) may reduce the severity of cerebral vasospasm and improve outcome, however, underlying mechanisms are incompletely understood. In this study, the authors aimed to investigate the effect of EPO on cerebral metabolism and brain tissue oxygen tension (PbtO2). METHODS: Seven consecutive poor grade SAH patients with multimodal neuromonitoring (MM) received systemic EPO therapy (30.000 IU per day for 3 consecutive days) for severe cerebral vasospasm. Cerebral perfusion pressure (CPP), mean arterial blood pressure (MAP), intracranial pressure (ICP), PbtO2 and brain metabolic changes were analyzed during the next 24 hours after each dose given. Statistical analysis was performed with a mixed effects model. RESULTS: A total of 22 interventions were analyzed. Median age was 47 years (32-68) and 86% were female. Three patients (38%) developed DCI. MAP slightly decreased 2 hours after intervention (P<0.04) without significantly affecting CPP and ICP. PbtO2 significantly increased over time (P<0.05) to a maximum of 7+/-4mmHg increase 16 hours after infusion. Brain metabolic parameters did not change over time. CONCLUSIONS: EPO increases PbtO2 in poor grade SAH patients with severe cerebral vasospasm. The effect on outcome needs further investigation.
    BMC Neurology 06/2012; 12(1):32. · 2.56 Impact Factor
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    ABSTRACT: Biological repair strategies for the treatment of degenerated intervertebral discs are of growing interest. In addition to the development of nucleus pulposus implants to restore disc height and relieve pain, there is growing demand for an appropriate method for reconstructing the anulus fibrosus (AF). The aim of this pilot study was to evaluate the applicability of a resorbable 3D polymer of pure polyglycolic acid (PGA) combined with hyaluronan for the use in cell-free and cell-based regeneration and repair of the AF. Adult human AF cells were expanded in vitro using human serum and rearranged three dimensionally in hyaluronan-PGA scaffolds that were stabilized with fibrin for in vitro analyses. The capacity of dedifferentiated AF cells to redifferentiate was evaluated after 2 weeks of culture, using propidium iodide/fluorescein diacetate staining, gene expression analysis of typical marker genes, and histological staining of proteoglycans. The propidium iodide/fluorescein diacetate staining demonstrated that vital human AF cells were evenly distributed within the construct. The induction of typical AF marker genes such as collagen Types I-III indicated the initiation of AF redifferentiation by 3D assembly in hyaluronan-PGA. Histological analysis of the constructs showed initial formation of an AF-like matrix comprising proteoglycans. The results suggest that the 3D arrangement of human AF cells in resorbable hyaluronan-PGA scaffolds cultured in the presence of human serum is an excellent system for AF cell redifferentiation.
    Journal of neurosurgery. Spine 05/2012; 17(2):177-83. · 1.61 Impact Factor
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    ABSTRACT: Xenon-enhanced computed tomography (XeCT) allows quantification of hemodynamic insufficiency in the setting of cerebrovascular atherosclerotic disease (CAD). However, data regarding the relationship between hemodynamic indices [cerebral blood flow (CBF) and cerebrovascular reserve capacity (CVRC)] and normal subjects (with aging) and pathology (progression of CAD or development of stroke symptoms) are limited. In this study, we analyzed 103 consecutive patients undergoing XeCT according to age, anatomical location and disease severity. We stratified anatomically defined ROIs according to a classification system that observes the presence of proximal stenosis (class I vs. class II/III) as well as the presence of neurological symptoms (class II vs. III); CBF, CVRC and hemodynamic stress distribution were calculated. Supratentorial CBF decreases significantly with age, but not infratentorially. Cortical CVRC remains stable over time. Our classification of disease severity correlated highly significantly with a decrease in supratentorial CBF and CVRC, though CVRC is less sensitive to age-related changes. Regression analysis delineated a CVRC of 34% to discriminate between ROI classes. Age-dependent perfusion characteristics in normal vascular territories were characterized. In CAD, CVRC remains the most sensitive parameter. A simplified classification of ROIs according to disease severity correlates well with established markers for hemodynamic insufficiency. It may facilitate comparison of different pathologies such as CAD and Moyamoya disease and will be the focus of further studies.
    Translational Stroke Research 03/2012; 3(1):122-9.

Publication Stats

1k Citations
241.28 Total Impact Points

Institutions

  • 2013
    • RWTH Aachen University
      Aachen, North Rhine-Westphalia, Germany
    • University Hospital RWTH Aachen
      Aachen, North Rhine-Westphalia, Germany
  • 2010–2013
    • University of Innsbruck
      • Institute of Analytical Chemistry and Radiochemistry
      Innsbruck, Tyrol, Austria
  • 2000–2013
    • Universität Heidelberg
      • • Faculty of Medicine Mannheim and Clinic Mannheim
      • • Surgical Hospital
      Heidelburg, Baden-Württemberg, Germany
  • 2008–2012
    • Charité Universitätsmedizin Berlin
      Berlín, Berlin, Germany
  • 2011
    • Medizinische Universität Innsbruck
      • Univ.-Klinik für Neurochirurgie
      Innsbruck, Tyrol, Austria
  • 2003–2011
    • Universität Mannheim
      Mannheim, Baden-Württemberg, Germany