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  • 1
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    Distinct serum and cerebrospinal fluid cytokine and chemokine profiles in autoantibody-associated demyelinating diseases
    SAGE Publications ; 2019
    In:  Multiple Sclerosis Journal - Experimental, Translational and Clinical Vol. 5, No. 2 ( 2019-04), p. 205521731984846-
    Details
    In: Multiple Sclerosis Journal - Experimental, Translational and Clinical, SAGE Publications, Vol. 5, No. 2 ( 2019-04), p. 205521731984846-
    Abstract: Demyelinating diseases of the central nervous system associated with autoantibodies against aquaporin-4 and myelin-oligodendrocyte-glycoprotein are mediated by different immunopathological mechanisms compared to multiple sclerosis. Objective The purpose of this study was to evaluate serum and cerebrospinal fluid cytokine/chemokine profiles in patients with autoantibodies against aquaporin-4 or autoantibodies against myelin-oligodendrocyte-glycoprotein-associated demyelination compared to multiple sclerosis and autoimmune encephalitis. Methods Serum and cerebrospinal fluid cytokine/chemokine levels were analysed using Procartaplex Multiplex Immunoassays. First, we analysed a panel of 32 cytokines/chemokines in a discovery group (nine aquaporin-4-antibody seropositive, nine myelin oligodendrocyte glycoprotein-antibody seropositive, eight encephalitis, 10 multiple sclerosis). Significantly dysregulated cytokines/chemokines were validated in a second cohort (11 aquaporin-4-antibody seropositive, 18 myelin oligodendrocyte glycoprotein-antibody seropositive, 18 encephalitis, 33 multiple sclerosis). Results We found 11 significantly altered cytokines/chemokines in cerebrospinal fluid and serum samples in the discovery group (a proliferation-inducing ligand, fractalkine=CX3CL1, growth-regulated oncogene-α, interleukin-1 receptor antagonist, interleukin-6, interleukin-8=CXCL8, interleukin-10, interleukin-21, interferon-ɣ-induced protein-10=CXCL10, monokine induced by interferon-ɣ=CXCL9, macrophage inflammatory protein-1ß=CCL4). Most of these cytokines/chemokines were up-regulated in autoantibodies against aquaporin-4 or autoantibodies against myelin-oligodendrocyte-glycoprotein positive patients compared to multiple sclerosis. We confirmed these results for cerebrospinal fluid interleukin-6 and serum interleukin-8, growth-regulated oncogene-α, a proliferation-inducing ligand and macrophage inflammatory protein-1β in the validation set. Receiver-operating characteristic analysis revealed increased levels of cerebrospinal fluid interleukin-6, serum interleukin-8 and growth-regulated oncogene-α in most patients with autoantibody-associated neurological diseases. Conclusion This study suggests that distinctive cerebrospinal fluid and serum cytokine/chemokine profiles are associated with autoantibody-mediated demyelination, but not with multiple sclerosis.
    Type of Medium: Online Resource
    ISSN: 2055-2173 , 2055-2173
    URL: Article
    DOI: 10.1177/2055217319848463
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2019
    detail.hit.zdb_id: 2841884-0
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  • 2
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    Effect of intra-aortic balloon pump support on microcirculation during high-risk percutaneous intervention
    SAGE Publications ; 2009
    In:  Perfusion Vol. 24, No. 6 ( 2009-11), p. 417-421
    Details
    In: Perfusion, SAGE Publications, Vol. 24, No. 6 ( 2009-11), p. 417-421
    Abstract: Background: Intra-aortic balloon counter-pulsation (IABP) is recommended for hemodynamic support in cardiogenic shock. In addition, it can be applied during high-risk percutaneous interventions (PCI). While IABP support improves microflow in cardiogenic shock, its effect in hemodynamically stable patients is still unclear. We, therefore, sought to evaluate the effect of IABP treatment on microflow in hemodynamically stable patients undergoing elective high-risk PCI. Methods: In six patients with 〉 " xbd="892" xhg="869" ybd="1310" yhg="1284"/ 〉 50% left main stenosis, microflow was evaluated according to current guidelines, using side-stream dark-field microscopy, visualizing microcirculatory vessels without using fluorescent dyes. Microflow was analyzed separately for each vessel category (diameter: 10-25µm and 26-50µm), using a semiquantitative system (0= no flow; 1= intermittent flow; 2= sluggish flow; 3= continuous flow) by a trained investigator. Steady state recordings and additional recordings twenty seconds after discontinuation of the electively implanted IABP were acquired. Results: Microflow in vessel categories 10-25µm and 26-50µm increased in this group of hemodynamically stable patients on use of IABP. Microflow decreased from 2.73±0.39 (p=0.052; 26-50µm: 2.88±0.20, p=0.008) to 2.22±0.23 (2.18±0.45) after stopping the IABP and increased to 2.90±0.14 (p=0.009; 2.85±0.28, p=0.009) after restart of the IABP. Conclusions: Circulatory support with IABP increases microcirculatory flow in the smallest vessels of the sublingual mucosa. Our data support the hypothesis that intra-aortic balloon counter-pulsation increases coronary and microvascular perfusion, thus, improving microcirculation even in hemodynamically stable patients. The use of IABP may increase safety of complex PCI and decrease the risk of deleterious complications.
    Type of Medium: Online Resource
    ISSN: 0267-6591 , 1477-111X
    URL: Article
    DOI: 10.1177/0267659109358208
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2009
    detail.hit.zdb_id: 2029611-3
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  • 3
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    New, optimized, dual-lumen cannula for veno-venous ECMO
    SAGE Publications ; 2018
    In:  Perfusion Vol. 33, No. 1_suppl ( 2018-05), p. 18-23
    Details
    In: Perfusion, SAGE Publications, Vol. 33, No. 1_suppl ( 2018-05), p. 18-23
    Abstract: The present study was designed to assess in vivo a new, optimized, virtually wall-less, dual-lumen, bi-caval cannula for veno-venous ECMO in comparison to a commercially available cannula. Methods: Veno-venous extracorporeal membrane oxygenation (ECMO) was carried out in a bovine study (n=5, bodyweight 75±5kg). Following systemic heparinization, ECMO was established in a trans-jugular fashion through a calibrated 23F orifice, using a new, optimized, virtually wall-less, dual-lumen, bi-caval 24F cannula (Smartcanula LLC, Lausanne, Switzerland) versus a commercially available 23F bi-caval, dual-lumen control cannula (Avalon Elite ® , Maquet, Rastatt, Germany) in a veno-venous ECMO setup. Veno-venous ECMO was initiated at 500 revolutions per minute (RPM) and increased by incremental steps of 500 RPM up to 2500 RPM. Catheter outlet pressure, catheter inlet pressure, oxygen saturation and pump flow were recorded at each stage. Results: Mean flow accounted for 0.37±0.04 L/min for wall-less versus 0.29± 0.07 L/min for control at 500 RPM, 0.97±0.12 versus 0.67±0.06 at 1000 RPM, 1.60±0.14 versus 1.16±0.08 at 1500 RPM, 2.31±0.13 versus 1.52±0.13 for 2000 RPM and 3.02±0.5 versus 2.11±0.18 (p 〈 0.004). The mean venous suction required was 19±8 mmHg for wall-less versus 20±3 mmHg for control at 500 RPM, 7±3 versus 9±4 for 1000 RPM, -11±10 versus -12±8 at 1500 RPM, -39±15 versus -49±10 for 2000 RPM and -60±28 versus -94±7 for 2500 RPM. The mean venous injection pressure accounted for 29±7 mmHg for wall-less versus 27±5 mmHg for control at 500 RPM, 50±6 versus 61±7 at 1000 RPM, 89±10 versus 99±17 for 1500 RPM, 142±14 versus 161±9 at 2000 RPM and 211±41 versus 252 ±3 for 2500 RPM. Conclusion: Compared to the commercially available control cannula, the new, optimized, virtually wall-less, dual-lumen, bi-caval 24F cannula allows for significantly higher blood flows, requires less suction and results in lower injection pressures in vivo.
    Type of Medium: Online Resource
    ISSN: 0267-6591 , 1477-111X
    URL: Article
    DOI: 10.1177/0267659118765597
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2018
    detail.hit.zdb_id: 2029611-3
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  • 4
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    Acute right heart failure: future perspective with the PERKAT RV pulsatile right ventricular support device
    SAGE Publications ; 2020
    In:  Therapeutic Advances in Cardiovascular Disease Vol. 14 ( 2020-01), p. 175394471989590-
    Details
    In: Therapeutic Advances in Cardiovascular Disease, SAGE Publications, Vol. 14 ( 2020-01), p. 175394471989590-
    Abstract: Acute right heart failure is associated with impaired prognosis in cardiogenic shock. Since most pharmacological therapies are not evaluated for the failing right ventricle, or even contraindicated, there is a need for rapid minimal invasive circulatory right heart support. The PERKAT RV is such a device for acute therapy in congestive heart failure. It reduces the central venous pooling by pumping blood from the inferior vena cava into the pulmonary artery with flow rates of up to 4 litres/min. The device was evaluated in an animal model of acute pulmonary embolism after careful in vitro tests. PERKAT RV increased cardiac output by 59% in sheep suffering from acute right heart failure. We await the first human implantation in the near future. Based on the PERKAT concept, future devolvement will also focus on left heart support.
    Type of Medium: Online Resource
    ISSN: 1753-9447 , 1753-9455
    URL: Article
    DOI: 10.1177/1753944719895902
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
    detail.hit.zdb_id: 2387507-0
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  • 5
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    New bidirectional arterial perfusion device
    SAGE Publications ; 2020
    In:  The International Journal of Artificial Organs Vol. 43, No. 7 ( 2020-07), p. 433-436
    Details
    In: The International Journal of Artificial Organs, SAGE Publications, Vol. 43, No. 7 ( 2020-07), p. 433-436
    Type of Medium: Online Resource
    ISSN: 0391-3988 , 1724-6040
    URL: Article
    DOI: 10.1177/0391398820901842
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
    detail.hit.zdb_id: 1474999-3
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  • 6
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    In vitro Evaluation of a Novel Pulsatile Right Heart Assist Device - the Perkat System
    SAGE Publications ; 2015
    In:  The International Journal of Artificial Organs Vol. 38, No. 10 ( 2015-10), p. 537-541
    Details
    In: The International Journal of Artificial Organs, SAGE Publications, Vol. 38, No. 10 ( 2015-10), p. 537-541
    Abstract: Acute right ventricular failure is a life-threatening condition with poor prognosis. It occurs as a result of right ventricular infarction, postcardiac transplantation, or postimplantation of a left ventricular assist device. Temporary mechanical right ventricular support could be a reasonable treatment option. Therefore, we developed a novel percutaneously implantable device. Methods The PERKAT device consists of a self-expandable chamber covered with multiple inflow valves carrying foils. A flexible outlet tube with a pigtail tip is attached to the distal end. PERKAT is designed for percutaneous implantation through the femoral vein (18 French sheath). The chamber is expanded in the inferior vena cava while the outlet tube bypasses the right heart and the pigtail tip is lying in the pulmonary trunk. An IABP balloon is inserted into the chamber and connected to an IABP console. Balloon deflation generates blood flow from the vena cava into the chamber through the foil valves. During inflation blood is pumped through the tube into the pulmonary arteries. Results In vitro experiments were performed using 30 mL and 40 mL IABP balloons. IABP inflation/deflation times were set to 80, 90, 100, and 110 per min with an afterload of 22 mmHg and 44 mmHg. PERKAT generated flow rates between 1.6 to 3.1 l/min, depending on balloon size, pump cycle, and afterload. Conclusions The novel percutaneously implantable right ventricular assist device offers emergency support of up to 3 l/min. Based on the successful in vitro evaluation, we recommend the system as a promising approach for treatment of patients in need of RV support.
    Type of Medium: Online Resource
    ISSN: 0391-3988 , 1724-6040
    URL: Article
    DOI: 10.5301/ijao.5000440
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2015
    detail.hit.zdb_id: 1474999-3
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  • 7
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    Understanding migraine using dynamic network biomarkers
    SAGE Publications ; 2015
    In:  Cephalalgia Vol. 35, No. 7 ( 2015-06), p. 627-630
    Details
    In: Cephalalgia, SAGE Publications, Vol. 35, No. 7 ( 2015-06), p. 627-630
    Abstract: Mathematical modeling approaches are becoming ever more established in clinical neuroscience. They provide insight that is key to understanding complex interactions of network phenomena, in general, and interactions within the migraine-generator network, in particular. Purpose In this study, two recent modeling studies on migraine are set in the context of premonitory symptoms that are easy to confuse for trigger factors. This causality confusion is explained, if migraine attacks are initiated by a transition caused by a tipping point. Conclusion We need to characterize the involved neuronal and autonomic subnetworks and their connections during all parts of the migraine cycle if we are ever to understand migraine. We predict that mathematical models have the potential to dismantle large and correlated fluctuations in such subnetworks as a dynamic network biomarker of migraine.
    Type of Medium: Online Resource
    ISSN: 0333-1024 , 1468-2982
    URL: Article
    DOI: 10.1177/0333102414550108
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2015
    detail.hit.zdb_id: 2019999-5
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  • 8
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    Acute treatment of migraine with the selective 5-HT 1F receptor agonist lasmiditan – A randomised proof-of-concept trial
    SAGE Publications ; 2010
    In:  Cephalalgia Vol. 30, No. 10 ( 2010-10), p. 1170-1178
    Details
    In: Cephalalgia, SAGE Publications, Vol. 30, No. 10 ( 2010-10), p. 1170-1178
    Abstract: Introduction: Lasmiditan (COL-144; LY573144) is a novel, highly selective and potent agonist at 5-HT 1F receptors that lacks vasoconstrictor activity. Preclinical and early clinical experiments predict acute antimigraine efficacy of COL-144 that is mediated through a non-vascular, primarily neural, mechanism. Subjects and methods: In a randomised, multicentre, placebo-controlled, double-blind, group-sequential, adaptive treatment-assignment, proof-of-concept and dose-finding study, we treated 130 subjects in-hospital during a migraine attack. Subjects were allocated to an intravenous dose level of lasmiditan or placebo in small cohorts. The starting dose was 2.5 mg. Subsequent doses were adjusted, up or down, according to the safety and efficacy seen in the preceding cohort. The primary outcome measure was headache response defined as improvement from moderate or severe headache at baseline to mild or no headache at 2 h post-dose. The study was designed to explore the overall dose response relationship but was not powered to differentiate individual doses from placebo, nor to detect effect differences for other migraine symptoms. Results: Forty-two subjects received placebo and 88 received lasmiditan in doses of 2.5–45 mg. Subjects were observed in the clinic for 4 h after treatment and used a diary card to record symptoms and adverse events for up to 24 h. The study was terminated when the 20 mg dose met predefined efficacy stopping rules. Of subjects treated in the 10, 20, 30 and 45 mg lasmiditan dose groups, 54–75% showed a 2 h headache response, compared to 45% in the placebo group ( P = 0.0126 for the linear association between response rates and dose levels). Patient global impression at 2 h and lack of need for rescue medication also showed statistically significant linear correlations with dose. Lasmiditan was generally well tolerated. Adverse events were reported by 65% of subjects on lasmiditan and by 43% on placebo and were generally mild. Dizziness, paresthesia and sensations of heaviness (usually limb) were more common on lasmiditan. Conclusions: At intravenous doses of 20 mg and higher, lasmiditan proved effective in the acute treatment of migraine. Further studies to assess the optimal oral dose and full efficacy and tolerability profile are under way. The non-vascular, neural mechanism of action of lasmiditan may offer an alternative means to treat migraine especially in patients who have contra-indications for agents with vasoconstrictor activity. The clinicaltrials.gov identifier for this study is NCT00384774.
    Type of Medium: Online Resource
    ISSN: 0333-1024 , 1468-2982
    URL: Article
    DOI: 10.1177/0333102410375512
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2010
    detail.hit.zdb_id: 2019999-5
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  • 9
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    Recording, analysis, and interpretation of spreading depolarizations in neurointensive care: Review and recommendations of the COSBID research group
    SAGE Publications ; 2017
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 37, No. 5 ( 2017-05), p. 1595-1625
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    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 37, No. 5 ( 2017-05), p. 1595-1625
    Abstract: Spreading depolarizations (SD) are waves of abrupt, near-complete breakdown of neuronal transmembrane ion gradients, are the largest possible pathophysiologic disruption of viable cerebral gray matter, and are a crucial mechanism of lesion development. Spreading depolarizations are increasingly recorded during multimodal neuromonitoring in neurocritical care as a causal biomarker providing a diagnostic summary measure of metabolic failure and excitotoxic injury. Focal ischemia causes spreading depolarization within minutes. Further spreading depolarizations arise for hours to days due to energy supply-demand mismatch in viable tissue. Spreading depolarizations exacerbate neuronal injury through prolonged ionic breakdown and spreading depolarization-related hypoperfusion (spreading ischemia). Local duration of the depolarization indicates local tissue energy status and risk of injury. Regional electrocorticographic monitoring affords even remote detection of injury because spreading depolarizations propagate widely from ischemic or metabolically stressed zones; characteristic patterns, including temporal clusters of spreading depolarizations and persistent depression of spontaneous cortical activity, can be recognized and quantified. Here, we describe the experimental basis for interpreting these patterns and illustrate their translation to human disease. We further provide consensus recommendations for electrocorticographic methods to record, classify, and score spreading depolarizations and associated spreading depressions. These methods offer distinct advantages over other neuromonitoring modalities and allow for future refinement through less invasive and more automated approaches.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    URL: Article
    DOI: 10.1177/0271678X16654496
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2017
    detail.hit.zdb_id: 2039456-1
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