bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetisch bedingte Aortenerkrankungen – Empfehlungen für Kardiologen in Praxis und Klinik
Authors: Huntgeburth Michael , Neidenbach Rhoia , von Kodolitsch Yskert , Kaemmerer Harald 
Published: June 2018

ZusammenfassungErweiterungen der Aorta sind häufig. Erst die Kenntnis zugrunde liegender Ursachen und Mechanismen ermöglicht eine adäquate Diagnose und Beratung der Betroffenen. Genetisch bedingte Aortenerkrankungen sind mit einem erhöhten Risiko für Aortenkomplikationen wie Dissektion und Ruptur assoziiert. Die zugrunde liegenden Ursachen können syndromal (z. B. Marfan-, Loeys-Dietz-, vaskuläres Ehlers-Danlos-Syndrom) und nicht syndromal (z. B. isolierte bikuspide Aortenklappe – BAV, Aortenisthmusstenose, komplexe angeborene Herzfehler, familiäres thorakales Aortenaneurysma – FTAA, Dissektionen – TAAD) bedingt sein. Familienanamnese, klinische Merkmale, Bildgebung und genetische Testung werden zur Diagnosestellung herangezogen. Entscheidend ist eine genaue prognostische Einschätzung hinsichtlich möglicher Aortenkomplikationen. Das Management umfasst eine Modifikation der Lebensweise (z. B. bez. körperlicher Belastung bei Sport und Beruf), eine medikamentöse Prophylaxe einer progressiven Aortenerweiterung (Reduzierung der Wandspannung), eine elektive Aortenersatz-OP sowie regelmäßige Nachsorgeuntersuchungen. Aufgrund der Komplexität der Aortopathien ist eine multidisziplinäre Betreuung für eine optimale Patientenversorgung notwendig. Zudem sollte ein Familienscreening von Angehörigen ersten Grades erfolgen, um gefährdete Familienmitglieder identifizieren zu können.
Die Umsetzung des Präventionsgesetzes auf Länderebene: Eine Analyse der Landesrahmenvereinbarungen
Authors: Böhm Katharina , Klinnert Dorothea 
Published: June 2018

Zusammenfassung
Hintergrund 2015 wurde in Deutschland erstmals ein Präventionsgesetz verabschiedet. Zur Umsetzung auf Länderebene werden Landesrahmenvereinbarungen (LRVen) zwischen den Sozialversicherungsträgern und den zuständigen Landesministerien getroffen.
Ziel der Arbeit Der Beitrag gibt einen Überblick über die 15 bislang abgeschlossenen LRVen und arbeitet Unterschiede und Gemeinsamkeiten zwischen den Ländern heraus.
Methode Die LRVen wurden einer qualitativen Inhaltsanalyse unterzogen. Hierfür wurden zunächst für jeden Paragraphen Abweichungen von der von den Sozialversicherungsträgern auf Bundesebene konsentierten Mustervorlage festgestellt. In einem zweiten Schritt wurden die Abweichungen einander paragraphenweise gegenübergestellt und Unterkategorien gebildet. Anschließend wurden die Inhalte der Kategorien entsprechend ihrer Merkmalsausprägungen kodiert. Für diesen Beitrag wurden 4 Kategorien ausgewählt: Ziele und Handlungsfelder, Gremien und Regelungsstrukturen, Vorgaben zur Kooperation, sowie Zusammenarbeit mit weiteren Akteuren.
Ergebnisse In einigen LRVen werden über die Ziele der Bundesrahmenempfehlungen hinaus ergänzend landesspezifische Ziele formuliert. Ein Zieleplanungsprozess findet teils innerhalb der LRV-Gremien, teils in breiter angelegten Prozessen statt. Mit 2 Ausnahmen schaffen die LRVen in allen Ländern neue Regelungsstrukturen, welche sich jedoch in ihrer Interaktionsorientierung unterscheiden: in 4 Ländern sind dialogorientierte, in 3 Ländern abstimmungsorientierte und in 7 Ländern entscheidungsorientierte Gremien bzw. Foren in der LRV verankert. Die Vorgaben zur Koordinierung sind in den meisten LRVen weitgehend unverbindlich. Auch die Zusammenarbeit mit dem ÖGD und weiteren relevanten Akteuren wird zumeist nicht oder nur unverbindlich geregelt.
Schlussfolgerungen Die meisten LRVen sind sehr allgemein und wenig verbindlich formuliert; sie definieren lediglich den Rahmen, den es nun auszufüllen gilt. Eine Evaluation der Umsetzung wird daher erst in ein paar Jahren möglich sein.
Genetik von Vorhofflimmern
Authors: Sinner Moritz , Clauss Sebastian , Kääb Stefan 
Published: June 2018

ZusammenfassungVorhofflimmern ist die häufigste Herzrhythmusstörung und betrifft mehrere Millionen Menschen weltweit. Nachdem in den letzten Jahren bereits ein starker genetischer Einfluss auf die Entstehung von Vorhofflimmern nachgewiesen worden war, konnte eine Studie kürzlich die Heritabilität von Vorhofflimmern mit 22,1% quantifizieren. Klinisch spiegelt sich dies in der Bedeutung der Familienanamnese für Vorhofflimmern wider. Neben seltenen Mutationen, etwa in Ionenkanalgenen, stellen insbesondere häufige genetische Varianten, sog. Single Nucleotide Polymorphisms, einen entscheidenden Faktor der Heritabilität von Vorhofflimmern dar. Mithilfe genomweiter Assoziationsstudien konnten mittlerweile 97 Genorte identifiziert werden, die mit einem erhöhten Risiko für das Auftreten von Vorhofflimmern assoziiert sind. Obwohl die meisten dieser Polymorphismen in der Nachbarschaft von elektrophysiologisch relevanten Genen, kardialen Strukturgenen oder entwicklungsbiologisch relevanten Genen liegen, sind die dem erhöhten Vorhofflimmerrisiko zugrunde liegenden zellulären und molekularen Mechanismen in vielen Fällen unbekannt. Um dies aufzuklären, sind umfangreiche Untersuchungen in zell- und tierexperimentellen Modellen notwendig.
Rupture of the Free Left Ventricular Wall: A Novel Approach for Reconstruction
Authors: Fleißner Felix , Schmitto Jan , Napp L. Christian , Ismail Issam 
Published: June 2018

Background A rupture of the free wall of the left ventricle is a rarely seen complication of myocardial infarction and represents an absolute cardiac emergency.
Case Description We hereby present a case of a 64-year-old patient with a rupture of the free left ventricular wall. The patient was treated in an emergent operation with a novel reconstruction method of the left ventricular wall and was discharged 30 days after the initial operation.
Conclusion Left ventricular free wall rupture is rarely described in the literature, which might be because of high mortality in underdiagnosed cases. Therefore, early imaging by echo or computed tomography (CT) is essential for detecting this dangerous condition. Once diagnosed, urgent surgery is mandatory to save the life of the patient.
The Effects of Human Thrombomodulin on the Inactivation of Thrombin by Its Serum Inhibitors
Authors: Thompson E Anne , Salem Hatem H 
Published: June 2018

SummaryThrombomodulin is an endothelial cell protein which accelerates thrombin-dependent protein C activation by over 1000 fold. In this study, the effect of thrombomodulin on the inactivation of thrombin by its serum inhibitors was evaluated.
125I-thrombin was incubated at 37° C with serum and the resulting complexes separated by SDS-PAGE. Antithrombin III was the major complex formed with some 125I-thrombin bound to heparin cofactor II and highermolecular weight fractions. Inclusion of thrombomodulin at increasing concentrations inhibited 125I-thrombin binding to antithrombin III and the higher molecular weight fractions but had little effect on thrombin-heparin cofactorII complex formation. Similar results were obtained using a purified antithrombin III/heparin cofactor II system.Kinetic studies, using purified antithrombin III, revealed that thrombomodulin acts as a weak competitive inhibitor towards antithrombin III (Ki = 39 nM).We postulate that in the microcirculation, where the ratio of thrombomodulin to antithrombin III is relatively high, thrombin bound to thrombomodulin may be protected from inactivation by antithrombin III and can thus promote efficient activation of protein C.
Multicenter Evaluation of a Chromogenic Substrate Method for Photometric Determination of Prothrombin Time
Authors: Dati F , Barthels M , Conard J , Flückiger J , Girolami A , Hänseler E , Huber J , Keller F , Kolde H -J , Müller-Berghaus G , Samama M , Thiel W 
Published: June 2018

SummaryA multicenter study of a chromogenic substrate method for photometric determination of prothrombin time was conducted in order to evaluate its clinical application. Seven laboratories pailicipaled in the study using a total of 742 plasma samples from 417 patients on oral anticoagulant therapy, 261 healthy subjects and 64 patients with different diseases especially of the liver as well as 30 patients with hereditary deficiency of coagulation factors II, V, VII, X. The chromogenic PT method was compared to a standardized coagulometric PT assay which uses the same sensitive human placenta thromboplastin calibrated against international reference preparations. A high correlation of the prothrombin ratio values of the chromogenic and the coagulometric assay was obtained in 402 plasma samples (r = 0.940; y = 1.02x − 0.1). The study showed that the chromogenic PT reagent is sensitive to deficiency of the coagulation factors of the extrinsic pathway but not affected by heparin up to 1 IU/ml because of the heparin antagonist added. The precision (coefficient of variation) of the photometric method ranged between 0.6 and 3% (intraassay CV) and between 1.4 and 5.8 (interassay CV). The International Sensitivity Index (ISI) obtained for the used lot was 1.09. The therapeutical range in percentage activity for patients in a stable phase of an anticoagulant therapy was found to be from 15 to 27 percent of normal. The results of the clinical evaluation proved the good comparability of the new chromogenic PT test with coagulometric methods, its high factor sensitivity, good reproducibility and easy performance.
Measurement of Low Molecular Weight Heparin Ex Vivo Activities in Clinical Laboratories Using Various Anti-Xa Assays: Interlaboratory Variability and Requirement for an Agreed Low Molecular Weight Heparin Standard
Authors: Sié P , Aillaud M F , Prost D de , Droullé C , Forestier F , Guedj P , Juhan-Vague I , Polack B , Potron G , Roncato M , Roussi J , Sampol J , Aiach M 
Published: June 2018

SummaryThe only sensitive and convenient assay to assess the biological activity of low molecular weight heparins (LMWHs) is based on the potentiation of activated factor Xa inhibition. Several procedures for measuring the socalled anti Xa activity have been proposed. In this collaborative study including eight laboratories, we have used four different assays (three amidolytic and one clotting based methods) for measuring the anti Xa activity of ex vivo samples obtained after injecting three different LMWHs. The dispersion of the results obtained by calibration against standard heparin could be reduced by using any of the three LMWHs for calibration. A coefficient of variation less than 0.20 between values obtained in different laboratories using a variety of methods seems acceptable. However it is necessary to refer to a common international standard for expressing the results in units and to define, for each of the three products, the therapeutic range.
Deaggregation of In Vitro-Degranulated Human Platelets: Irreversibility of Aggregation May Be Agonist-Specific Rather Than Related to Secretion Per Se
Authors: Bauman Joan E , Joachim Reimers H , Heinrich Joist J 
Published: June 2018

SummaryBased on studies with thrombin, it has been proposed that human platelets exposed to strong release-inducing agents undergo irreversible aggregation and cannot be deaggregated without the use of proteolytic enzymes. We tested the hypothesis that irreversible human platelet aggregation occurs as a result of thrombin-specific platelet alterations rather than induction of the release reaction per se. Washed human platelets were exposed to either thrombin (THR) or the aminophospholipid N-(7-Nitro- 2,1,3-benzoxydiazol-4-yl) phosphatidylserine (NBD-PS) for 20 seconds. Both agents caused similarly extensive release of platelet dense- and α-granule contents. After neutralization of thrombin and NBD-PS, and addition of PGE1 and apyrase, the platelets were sedimented, resuspended and incubated at 37° C with gentle agitation. Single, disc-shaped, degranulated platelets which were recovered in both systems were capable of aggregation in response to a second exposure to aggregating and release- inducing stimuli. Deaggregation was more rapid, more extensive, and more reproducible with NBD-PS- than with THR-degranulated platelets. Platelets exposed to thrombin for longer than 20 seconds showed a progressive loss of deaggregability which was not observed after prolonged incubation with NBD-PS. These findings do not support the concept that extensive secretion per se causes irreversible aggregation of human platelets. Instead it appears that formation of irreversible linkages between platelets involves the specific, time-dependent interaction of THR with platelets, released fibrinogen and possibly one or more other substances secreted from platelets.
The Effect of the Intracellular Calcium Chelator Quin-2 on the Platelet Phosphoinositide Metabolism, Protein Phosphorylation and Morphology
Authors: de Chaffoy de Courcelles D , Roevens P , Verheyen F , Van Belle H , De Clerck F 
Published: June 2018

SummaryWhen human platelets prelabeled with [32P] orthophosphate were loaded with Quin-2, the 32P-incorporation in phosphatidic acid, phosphatidylinositol-4 phosphate and phosphatidylinositol-4,5 bisphosphate increased, that in phosphatidylinositol decreased. These effects occurred in a Quin-2-concentration- dependent manner. On stimulation of the serotonin-S2 receptor, signal transduction, measured as changes in labeling in phospholipids and phosphoproteins, was altered in the presence of the fluorophore. Microscopic evaluation illustrated that Quin-2 affected platelet morphology as well in resting as in stimulated platelets. A correlation between platelet shape change and myosin light chain phosphorylation was apparent.The data evidence that the Quin-2 that is widely used for fluorometric determination of intracellular Ca2+, affects the metabolism of inositol-containing phospholipids whose breakdown is a key event in Ca2i+-mobilization on excitatory platelet activation. These fluorophore-induced alterations might, besides the Ca2-chelating properties, play an important role in the Ca2+ dependent signalling processes in these cells.
Interaction of Thrombin and Factor Xa with Bovine Vascular Endothelial Cells, Smooth Muscle Cells and Rat Hepatoma Cells
Authors: Dryjski Maciej , Kuo Be-Sheng , Bjornsson Thorir D 
Published: June 2018

SummaryThe aims of the present investigation were to characterize the binding and inhibition of thrombin and factor Xa to bovine vascular endothelial cells (EC), bovine smooth muscle cells (SMC), and rat hepatoma cells (RHC), and to evaluate the effects of plasma constituents on their inhibition. The enzymatic activities of bovine thrombin and factor Xa were assayed using chromogenic substrates. After 10 min incubation with the cells, thrombin activity in the solution had decreased by about 20% and was subsequently recovered on the cell surfaces. When the cells with the surface-bound thrombin were incubated with defibrinogenated plasma or antithrombin III (AT-III) for 30 sec only about 10% and 20-40%, respectively, of the initial activity could be recovered. In similar experiments with factor Xa, initial activity in the solution had decreased by 10% after 10 min incubation, and was subsequently recovered from the cell surfaces. After 30 sec incubation with AT-III, no cell surface-bound factor Xa activity was detected, whereas 10% of the bound factor Xa activity was recovered after incubation with defibrinogenated plasma. It is concluded that thrombin and factor Xa are taken up and inhibited by EC, SMC and RHC cell surfaces in similar ratios, suggesting that cell surface-mediated inhibition of clotting factors is not restricted to vascular wall cells. The inactivation of factor Xa was dependent on AT-III, however, the inactivation of thrombin was further promoted by an additional unidentified plasma constituent.
An Approach to Assigning In Vitro Potency to Unfractionated and Low Molecular Weight Heparins Based on the Inhibition of Prothrombin Activation and Catalysis of Thrombin Inhibition
Authors: Ofosu F A , Smith L M , Anvari N , Blajchman M A 
Published: June 2018

SummaryUnfractionated and low molecular weight (LMW) heparins with good antithrombotic activity invariably catalyze thrombin inhibition and inhibit the appearance of thrombin activity in contact-activated plasma. Conversely, the antithrombotic efficacy of LMW heparins decreases as their ability to catalyze thrombin inhibition and to inhibit the appearance of thrombin activity in plasma decrease. The activated partial thromboplastin time (APTT) has proven a reliable test for assaying unfractionated heparin. We therefore compared 2 unfractionated and 3 LMW heparins on the basis of the minimum concentrations required to double the APTT of normal plasma and by then determined how this anticoagulant effect was achieved. The amount of unfractionated and LMW heparin which doubled the APTT was found to be equivalent to —0.25 antithrombin units. This concentration of each glycosaminoglycan completely inhibited prothrombin activation for 45 s after CaCl2 was added to contact-activated plasma; accelerated thrombin inhibition by purified antithrombin III by approximately 50-fold; and accelerated thrombin inhibition equally by anti thrombin III in undiluted plasma. This concentration of the three LMW heparins increased, by approximately 70fold, the rate of factor Xa inhibition by purified antithrombin III compared to the 50-fold increase seen with the two unfractionated heparins. These results thus suggest that tests based on the inhibition of prothrombin activation and/or on the catalysis of thrombin inhibition provide a useful basis for assigning in vitro potency to both unfractionated and LMW heparins.
Changes in Factor VIII Proteins After Cardiopulmonary Bypass in Man Suggest Endothelial Damage
Authors: Jones D K , Luddington R , Higenbottam T W , Scott J , Cavarocchi N , Reardon D , Calvin J , Wallwork J 
Published: June 2018

Summary16 patients undergoing coronary artery bypass grafting using cardiopulmonary bypass (CPB) had blood samples taken at various times before, during and up to 1 week after surgery for estimation of beta-thromboglobulin (BTG), alpha- 1-antichymo- trypsin (ACT), factor VIII procoagulant protein (VIII:C), von Willebrand factor antigen (vWF:Ag) and ristocetin co-factor (vWFiRiCoF). vWF:Ag and vWF:RiCoF rose during and following surgery in a different manner to ACT. At 1 week there was a significantly disproportionate rise in vWF: Ag compared to vWFiRiCoF which suggested a degree of pulmonary endothelial damage.Prostacyclin, which was administered to 8 of the patients during CPB, reduced platelet activation as measured by a reduction in the release of BTG and also attenuated the consumption of VIII: C. It had no effect on pulmonary endothelial damage as measured by the ratio of vWF: Ag to vWF: RiCoF.
Localization of the Inhibitory Site(s) of Pentosan Polysulphate in Blood Coagulation
Authors: Wagenvoord R , Hendrix H , Soria C , Hemker H C 
Published: June 2018

SummaryWe studied the inhibitory effect of pentosan polysulphate (PPS, Hémoclar®) on thrombin formation in blood coagulation. In contrast to a current hypothesis (1) the anti thrombin III independent effect of PPS on blood coagulation is not caused by preventing the binding of the factors IX, IXa, X, Xa, VIII, V, Va and II onto procoagulant phospholipids.We investigated the activation by thrombin of factors I, V and VIII. A strong inhibitory effect of PPS on factor VIII activation could be observed. Inhibition of the activation of factor V to the same extent requires about 30-fold higher concentrations of PPS, whereas the activation (clotting) of fibrinogen is not inhibited. The effect of PPS on factor VIIIa is two-fold: A) it inhibits its formation and B) it inhibits its function probably by the formation of a factor VIIIa-PPS complex.Prothrombinase, constituted of purified factors Xa, Va and phospholipids was not inhibited by PPS, neither were incomplete forms of this enzyme, lacking phospholipids or factor Va. The complete factor X activating enzyme (factors IXa, VIIIa and phospholipids), however, was strongly inhibited, but incomplete forms, lacking factor VIII, were not. The inhibition of the complete enzyme can be explained by reversible binding of PPS to factor VIIIa (causing an inhibition of its function) and it is not an effect on the enzymatic function of the complete enzyme. On saturation of the enzyme with an excess of factor VIIIa no inhibition by PPS is noticed.We postulate therefore that the antithrombin III independent inhibitory effect of PPS on thrombin generation on blood coagulation is by interaction with factor VIIIa. This effect is additional to the heparin-like action of PPS, i.e. potentiation of the activity of antithrombin III and/or heparin cofactor II. At concentrations attained during therapeutic use the action of pentosan polysulphate on factor VIIIa is the only one that will significantly inhibit the coagulation mechanism.
The Endothelial Cell and the Factor VIII Bypassing Activity of Prothrombin Complex Concentrate
Authors: Teitel Jerome M , Ni Hong-Yu , Freedman John J , Garvey M Bernadette 
Published: June 2018

SummarySome classical hemophiliacs have a paradoxical hemostatic response to prothrombin complex concentrate (PCC). We hypothesized that vascular endothelial cells (EC) may contribute to this “factor VIII bypassing activity”. When PCC were incubated with suspensions or monolayer cultures of EC, they acquired the ability to partially bypass the defect of factor VIII deficient plasma. This factor VIII bypassing activity distributed with EC and not with the supernatant PCC, and was not a general property of intravascular cells. The effect of PCC was even more dramatic on fixed EC monolayers, which became procoagulant after incubation with PCC. The time courses of association and dissociation of the PCC-derived factor VIII bypassing activity of fixed and viable EC monolayers were both rapid. We conclude that EC may provide a privileged site for sequestration of constituents of PCC which express coagulant activity and which bypass the abnormality of factor VIII deficient plasma.
Effects of Standard Heparin and a Low Molecular Weight Heparin (Kabi 2165) on Fibrinolysis
Authors: Agnelli Giancarlo , Borm Judocus , Cosmi Benilde , Levi Marcel , Cate Jan Wouter ten 
Published: June 2018

SummaryPrevious and recent reports have suggested a fibrinolysisenhancing property of standard heparin and low molecular weight heparins, but these observations have never been confirmed in a study fulfilling appropriate methodological criteria. The aim of this study was to evaluate the effect of standard heparin and a low molecular weight heparin (Kabi 2165) on fibrinolysis in a randomized cross-over double blind placebo controlled study. Six healthy volunteers received intravenously a bolus dose of the following treatments: placebo; standard heparin, 5,000 I.U.; Kabi 2165, 5,000 anti-Xa U; Kabi 2165,10,000 anti-Xa U. Before the injection and at established times thereafter, blood samples were collected for the following assays in plasma: t-PA activity, PA inhibitor activity, fibrin plate lysis area (FPLA), plasminogen, α2-antiplasmin, fibrinogen and anti-Xa activity. Placebo and Kabi 2165, 5,000 anti-Xa U, had no effect on t-PA plasma level. Standard heparin and Kabi 2165, 10,000 anti-Xa U, produced a statistically significant increase in t-PA level at 1 hour after the infusion. This increase lasted for at least 1 hour after the infusion. No effect of any treatment on PA inhibitor, plasminogen, FLPA, α2-antiplasmin and fibrinogen was observed. We conclude that an intravenous bolus dose of both standard heparin, 5,000 I.U. and Kabi 2165, 10,000 anti-Xa U produces a delayed and sustained increase in plasma t-PA.