Two novel oral anticoagulants, namely the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitor rivaroxaban, have recently been approved for treatment of atrial fibrillation. They ...differ in many ways from vitamin K antagonists, including rapid onset of action, shorter half-life, fewer drug-drug interactions, lack of a need for monitoring and no need for titration or dose adjustments. Commonly available global coagulation time assessments (e.g. prothrombin time and activated partial thromboplastin time) are highly influenced by rivaroxaban and dabigatran but these assays are relatively insensitive. Ideally these anticoagulant agents would be assessable using a sensitive and standardized test with a linear dose-response curve. Optimized assays are currently under investigation and may quantify the anticoagulant effect. At present the therapeutic ranges for dose adjustment have not yet been established.
The etiology of osteoporosis comprises environmental and genetic factors. This study investigated vitamin D deficiency and specific genetic alterations of bone metabolism in a group of 183 Turkish ...immigrants in Germany in comparison with 46 age and sex matched healthy German controls (females in both groups were pre-menopausal).
Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Serum levels of osteologic parameters were determined after overnight fasting. Polymorphisms of the vitamin D receptor (VDR) and lactase genes were genotyped using genomic DNA from peripheral leukocytes. Statistical analysis comprised student's t-test, Mann-Whitney rank sum test, Chi-square analysis and Fisher's exact test.
Severe 25-OH D₃ hypovitaminosis (83.1%) and elevated parathyroid hormone (82%) were common among immigrants. Osteoporosis but not osteopenia was more prevalent in immigrants. Among immigrants with osteoporosis, TRAP5b was elevated in 26.7%, and β-crosslaps in 13.3%. Only the FokI FF VDR-gene-polymorphism was significantly more prevalent among immigrants. In contrast, Ff-genotyped Turkish women exhibited significantly decreased BMD. Lactase polymorphisms were significantly more common among immigrants (84.2% vs. 30.4%) and the CC genotype was commonly associated with reduced BMD (41.6%) but rarely osteoporosis (8.4%).
Vitamin D deficiency, secondary hyperparathyroidism and osteoporosis are common among Turkish immigrants in Germany. Thus, in this population osteologic parameters and BMD should be analyzed and deficiencies be treated. Specifically, the VDR gene polymorphism FokI Ff is of clinical value in identifying females at risk of osteoporosis. In contrast, LCT polymorphisms, though common, do not appear to be a risk factor.
Based on a state-of-the-art review of prior research in all related domains, this book makes precise predictions about the expected effects of specific type and token frequency distributions in input ...floods and tests these in the second language classroom context.
Zusammenfassung
Die neuen Antikoagulanzien Rivaroxaban und Dabigatran wurden vor Kurzem zur Prophylaxe kardioembolischer Komplikationen bei Vorhofflimmern zugelassen. Weitere Substanzen werden ...demnächst folgen. Die neuen Antikoagulanzien unterscheiden sich in wesentlichen Punkten von den Vitamin-K-Antagonisten: Ihre Wirksamkeit tritt schneller ein, die inter- und intraindividuellen Schwankungen sind wesentlich geringer, sie haben eine deutlich kürzere Halbwertszeit und zeigen eine geringe Arzneimittelinteraktion. Im Alltag sind daher kein Monitoring und keine Dosisanpassung erforderlich. Rivaroxaban und Dabigatran können fast alle Gerinnungstests beeinflussen. Daher müssen das Antikoagulans und der Zeitpunkt der letzten Einnahme bei der Interpretation von Gerinnungsbefunden berücksichtigt werden. Zum Monitoring von Rivaroxaban und Dabigatran sollten Testsysteme verwendet werden, die eine möglichst lineare Dosis-Wirkungs-Beziehung zeigen. Für den direkten Faktor-Xa (FXa)-Inhibitor Rivaroxaban ist die Bestimmung der Anti-FXa-Einheiten und der Thromboplastinzeit (TPZ), gemessen in Sekunden, möglich; für den Thrombininhibitor Dabigatran sind die Thrombinzeit und die aktivierte partielle Thromboplastinzeit (APTT) geeignete Testparameter. Optimierte Gerinnungstests stehen inzwischen für beide Präparate zur Verfügung. Der Umkehrschluss, nämlich vom Ausmaß eines veränderten Gerinnungstests auf die Wirksamkeit einer Antikoagulation zu schließen, ist aktuell mit keinem Testsystem möglich.
Die neuen Antikoagulanzien Rivaroxaban und Dabigatran wurden vor Kurzem zur Prophylaxe kardioembolischer Komplikationen bei Vorhofflimmern zugelassen. Weitere Substanzen werden demnächst folgen. Die ...neuen Antikoagulanzien unterscheiden sich in wesentlichen Punkten von den Vitamin-K-Antagonisten: Ihre Wirksamkeit tritt schneller ein, die inter- und intraindividuellen Schwankungen sind wesentlich geringer, sie haben eine deutlich kürzere Halbwertszeit und zeigen eine geringe Arzneimittelinteraktion. Im Alltag sind daher kein Monitoring und keine Dosisanpassung erforderlich. Rivaroxaban und Dabigatran können fast alle Gerinnungstests beeinflussen. Daher müssen das Antikoagulans und der Zeitpunkt der letzten Einnahme bei der Interpretation von Gerinnungsbefunden berücksichtigt werden. Zum Monitoring von Rivaroxaban und Dabigatran sollten Testsysteme verwendet werden, die eine möglichst lineare Dosis-Wirkungs-Beziehung zeigen. Für den direkten Faktor-Xa (FXa)-Inhibitor Rivaroxaban ist die Bestimmung der Anti-FXa-Einheiten und der Thromboplastinzeit (TPZ), gemessen in Sekunden, möglich; für den Thrombininhibitor Dabigatran sind die Thrombinzeit und die aktivierte partielle Thromboplastinzeit (APTT) geeignete Testparameter. Optimierte Gerinnungstests stehen inzwischen für beide Präparate zur Verfügung. Der Umkehrschluss, nämlich vom Ausmaß eines veränderten Gerinnungstests auf die Wirksamkeit einer Antikoagulation zu schließen, ist aktuell mit keinem Testsystem möglich. Two novel oral anticoagulants, namely the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitor rivaroxaban, have recently been approved for treatment of atrial fibrillation. They differ in many ways from vitamin K antagonists, including rapid onset of action, shorter half-life, fewer drug-drug interactions, lack of a need for monitoring and no need for titration or dose adjustments. Commonly available global coagulation time assessments (e.g. prothrombin time and activated partial thromboplastin time) are highly influenced by rivaroxaban and dabigatran but these assays are relatively insensitive. Ideally these anticoagulant agents would be assessable using a sensitive and standardized test with a linear dose-response curve. Optimized assays are currently under investigation and may quantify the anticoagulant effect. At present the therapeutic ranges for dose adjustment have not yet been established.PUBLICATION ABSTRACT
Lepirudin, a recombinant hirudin, is a direct acting thrombin inhibitor that has been used as a heparin alternative in patients with heparin-induced thrombocytopenia requiring on-pump cardiac ...surgery. To evaluate the efficacy, safety, and clinical utility of lepirudin as a cardiopulmonary bypass (CPB) anticoagulant, we compared lepirudin with heparin in a routine CPB setting.
Twenty patients were randomly assigned to receive lepirudin (0.25 mg/kg b. w. bolus and 0.2 mg/kg b. w. added to the CPB priming) or heparin (400 U/kg b. w. bolus) with protamine reversal. Lepirudin and heparin anticoagulation during CPB was monitored using the ecarin clotting time or ACT, respectively and additional lepirudin (5 mg) or heparin (5000 U) boluses were administered.
The CPB circuit was performed in both groups without thromboembolic complications. Median blood loss during the first 36 hours was statistically higher ( P = 0.007) in the lepirudin group (1.226 +/- 316 ml) compared to the heparin group (869 +/- 189 ml). One patient of the lepirudin group developed pulmonary embolism 24 hours after surgery. This patient was tested homozygous for the FV-Leiden mutation.
Lepirudin provides effective CPB anticoagulation but induces a higher postoperative blood loss than heparin. Lepirudin should be restricted to patients undergoing CPB who cannot be exposed to heparin.
Heparin-induced thrombocytopenia is a strong risk factor for the development of arterial and venous thromboembolic events. In patients clinically suspected for HIT, immediate cessation of heparin ...treatment and continuation of anticoagulant treatment using alternative anticoagulants is mandatory in order to minimize the risk of thrombotic events. Alternative anticoagulants that have been successfully used in HIT include the direct acting thrombin inhibitors hirudin, bivalirudin and argatroban, and the heparinoid orgaran. In addition, there is growing evidence that the synthetic pentasaccharide fondaparinux is usable for the treatment of HIT patients. This short review summarizes the strategies of alternate anticoagulant treatment in HIT patients and also describes long-term treatment of HIT patients.
A first explicit connection between finitely presented commutative monoids and ideals in polynomial rings was used in 1958 by Emelichev yielding a solution for the word problem in commutative monoids ...by deciding the ideal membership problem. The aim of this paper is to show how congruences on monoids and groups can be characterized by ideals in the corresponding monoid and group rings. These characterizations allow to transfer well known results from the theory of string rewriting systems for presenting monoids and groups to the algebraic setting of subalgebras and ideals in monoid and group rings. Moreover, natural one-sided congruences defined by subgroups of a group are connected to one-sided ideals in the respective group ring and hence the subgroup problem and the ideal membership problem are directly related. For several classes of finitely presented groups we show explicitly how Gröbner basis methods are related to existing solutions of the subgroup problem that are based on rewriting methods. For the case of general monoids and submonoids weaker results are presented. In fact it becomes clear that string rewriting methods for monoids and groups can be lifted in a natural way to define reduction relations in monoid and group rings.
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