bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetic Studies with FVIII/von Willebrand Factor Concentrate Can Be a Diagnostic Tool to Distinguish between Subgroups of Patients with Acquired von Willebrand Syndrome
Authors: Lubetsky A. , Schliamser L. , Kotler A. , Tamarin I. , Luboshitz J. , Inbal A. 
Published: March 2018

SummaryAcquired von Willebrand syndrome (AVWS) has been associated mainly with monoclonal gammopathy of uncertain significance (MGUS), clonal lymphoproliferative or myeloproliferative disorders and autoimmunity. In the present work we studied 6 patients with AVWS: four with MGUS IgG (λ or κ), one with small lymphocytic lymphoma and one with agnogenic myeloid metaplasia (AMM). All the patients underwent a pharmacokinetic analysis at presentation in order to study potential differences in recovery, clearance (CL) or terminal half-life (THL) following administration of von Willebrand factor (VWF) concentrate. In all the patients with AVWS an increase in clearance and a decrease in THL was observed as compared to these parameters in patients with hereditary type 3 von Willebrand disease (VWD). No difference in recovery was observed among the groups. The increase in clearance and the decrease in THL were significantly more pronounced in the group of MGUS patients (57.93 ± 25.6 ml/h/kg, and 1.39 ± 0.5 h, respectively) as compared to these parameters in the AMM (8.06 ml/h/kg, and 6.96 h, respectively) or the lymphoma (4.76 ml/h/kg, and 6.76 h, respectively) patients (p = 0.03 for clearance and 0.001 for THL). These data indicate that the pharmacokinetic analysis can be a useful tool to distinguish between MGUS-related and other causes of AVWS, and to plan an appropriate treatment accordingly.
Extracellular Nucleotides ATP and UTP Induce a Marked Acute Release of Tissue-type Plasminogen Activator In Vivo in Man
Authors: Hrafnkelsdóttir Thórdís , Erlinge David , Jern Sverker 
Published: March 2018

SummaryExtracellular nucleotides such as ATP and UTP are released by activation of platelets and ischemic tissue injury. The aim of the present study was to investigate whether ATP and UTP can induce acute tPA release from the vascular endothelium in vivo. Nine healthy subjects were studied in a perfused-forearm model during stepwise intraarterial infusions of ATP and UTP (10-200 nmol/min), and UTP during inhibition of prostanoid and NO synthesis by indomethacin and L-NMMA. ATP and UTP induced a similar and marked stimulation of forearm tPA release which increased 11- and 18-fold above baseline (p ≤ 0.01 for both) in conjunction with pronounced vasodilation. Neither the acute tPA release nor the vasodilation could be abrogated by NO and prostanoid synthesis inhibition. The similar effect of ATP and UTP suggests that P2Y rather than adenosine receptors mediate the response. Release of extracellular nucleotides in ischemic tissue may induce a pronounced activation of the endogenous fibrinolytic system.
Telesprachtherapie (Synchrotel) bei Aphasie nach Schlaganfall
Authors: Richter J. , Scibor M. , Keidel M. , Vauth F. 
Published: March 2018

ZusammenfassungIn einer prospektiven Studie wurde die Effizienz telemedizinischer Online-Sprachtherapie bei Schlaganfall-Patienten überprüft. Studienziel war es, die Tele-Online-Therapie als neue zusätzliche Therapieform zu etablieren. Tele-Online-Sprachtherapie ist speziell für schwer und schwerstbetroffene chronische Patienten mit nicht flüssiger Aphasie geeignet. Sie bietet die Möglichkeit, Sprachtherapie hochfrequent und intensiv anzubieten. Dadurch können häufige Klinikaufenthalte eingespart werden. Es wurde eine neue Therapiemethode und spezifisch dafür konzipiertes Therapiematerial entwickelt: Das Konzept der interaktions-, emotions- und motivationsfokussierten Sprachtherapie. Die Ergebnisse bestätigen, dass Tele-Online-Therapie gleiche Wirkeffekte wie konventionelle Sprachtherapie zeigt. Entgegen der Ausgangserwartung zeigen sich häufiger positive Veränderungen in der Tele-Online-Therapiegruppe.
Pharmakotherapie des Parkinson
Authors: Ceballos-Baumann A. O. , Fietzek U. M. 
Published: March 2018

ZusammenfassungDie Suche nach besseren symptomatischen Parkinson-Therapeutika hat in den letzten Jahren zahlreiche Neuentwicklungen hervorgebracht. Levodopa ist weiterhin zentraler Therapiebaustein. Die Hersteller suchen nach Wegen, um den Nachteil der kurzen Plasmahalbwertszeit dieser Aminosäure zu kompensieren. In den USA ist eine neue Levodopa-Carbidopa-Galenik mit einer langsameren Wirkstoffreissetzung für fluktuierende Parkinson-Patienten neu auf dem Markt. Hierzu werden eine inhalative und eine subkutane Darreichungsform des Levodopa klinisch geprüft. Der einzige erst jüngst neu zugelassene neue Wirkstoff seit 2007, das Safinamid, beeinflusst die Monoaminooxidase (MAO) sowie den Glutamatstoffwechsel und verspricht mehr dopaminerge Wirkung ohne Auslösung von Dyskinesien. Neue COMT-Inhibitoren sollen ebenso das Levodopa mittels einer Hemmung dieses Abbauweges besser verfügbar machen. Ältere Substanzen wie der NMDA-Inhibitor Amantadin werden neu aufgelegt, um Levodopa induzierte Dyskinesien zu behandeln. Die Gruppe der mGluR5-Antagonisten zielen ebenso auf diese Indikation ab. Mehrere Adenosinantagonisten wurden entwickelt, um über nicht dopaminerge Mechanismen Parkinson-Symptome zu reduzieren. Das Pimavanserin ist ein inverser Serotoninagonist der an psychotischen Parkinson-Patienten erfolgreich geprüft wurde. Eine Studie zu parkinsonassoziierten Schmerzen untersuchte die Kombination Oxycodon und Naloxon bei schweren Schmerzen mit gemischten Ergebnissen. Noch nicht einzuschätzen sind die Möglichkeiten immunotherapeutischer Ansätze, z. B. die „Parkinson-Impfung“ und monoklonale Antikörper, gegen Alphasynuklein, die inzwischen klinisch untersucht werden.
Traumafolgestörungen in der Bundeswehr
Authors: Wesemann U. , Willmund G. , Alliger-Horn C. , Zimmermann P. 
Published: March 2018

ZusammenfassungDie Bundeswehr ist seit 1991 in Auslandseinsätzen engagiert. Der Stellenwert psychischer Erkrankungen hat sich in dieser Zeit deutlich erhöht und stellt nun eine erhebliche Herausforderung für Prävention und Therapie dar. Ziel dieses Beitrages ist es, einen Überblick über aktuelle Entwicklungen in den Bereichen Prävention, Behandlung, Begutachtung und Forschung zu psychischen Erkrankungen in der Bundeswehr zu geben und zu diskutieren.
Neuronale Korrelate emotionaler Dysregulation bei Patienten mit Borderline-Persönlichkeitsstörung
Authors: Viviani R. , Sosic-Vasic Z. , Schauer J. S. 
Published: March 2018

ZusammenfassungDie Borderline-Persönlichkeitsstörung (BPS) ist eine schwerwiegende psychiatrische Erkrankung, die insbesondere durch eine Störung der Emotionsregulation gekennzeichnet ist. Gängige neuronale Modelle der Emotionsregulation gehen davon aus, dass zwei Prozesse in diesem Zusammenhang von Bedeutung sind: einerseits ein ventrales neuronales Netzwerk, welches für die Emotionsentstehung entscheidend ist (bottom-up) und andererseits präfrontale neuronale Strukturen, die mittels kognitiver Kontrollmechanismen der Emotionsregulation dienen (top-down). Neuere Forschung weist auf die Bedeutung impliziter Emotionsregulation unabhängig von exekutiven Funktionen hin. Untersuchungen zu neuronalen Korrelaten emotionaler Dysregulation bei der BPS finden vor allem eine Hyperreaktivität der Amygdala, die als erhöhte Sensibilität für emotionale Reize und Grundlage emotionaler Instabilität gedeutet werden kann. Psychotherapeutische Ansätze zeigen dazu passend eine Reduktion dieser erhöhten emotionalen Sensitivität im Sinne reduzierter Amygdalaaktivierung in Folge der Behandlung. In Bezug auf die Mechanismen einer veränderten Emotionsregulation bleiben die Befunde uneindeutig, was der geringen Stichprobengröße und großen Methodenvariabilität, aber auch einer notwendigen Erweiterung von Emotions-regulationsmodellen geschuldet sein kann.
Clinical Prediction of Lower Limb Deep Vein Thrombosis in Symptomatic Hospitalized Patients
Authors: Nelzy M. L. , Salmi L. R. , Skopinski S. , Saby J. C. , Le Métayer P. , Morlat P. , Conri C. , Constans J. 
Published: March 2018

SummaryWe evaluated two clinical scores for the prediction of deep venous thrombosis (DVT) in hospitalized patients (Wells’ and Kahn’s). We included 273 patients referred to the vascular exploration unit for the suspicion of DVT. A clinical questionnaire was filled in by the practitioner and the scores were calculated from this form. 66 of the 273 patients had a DVT. When Wells’ score was 3, a DVT was found by duplex echography in 51% patients ; when the score was 0, a DVT was found in 9%. Kahn’s score was not adapted to this population. We then developed a new simple score (cancer, palsy or plaster immobilization, warmth, superficial venous dilation, unilateral pitting edema, other diagnosis). A DVT was found in 76% patients with a score of 3 and in 11% in those with a score of 0. We therefore propose a 6-item score whose main advantages are simplicity and usefulness in routine practice.
Creation of an Additional Glycosylation Site as a Mechanism for Type I Antithrombin Deficiency
Authors: Lewandowski Krzysztof , Olds Robin , Fitches Alison 
Published: March 2018

SummaryWe report the identification of a new mutation resulting in type I antithrombin (AT) deficiency and the mechanism by which the deficiency arose. The single base substitution of G to A at nucleotide 2709 was identified in a proband with a family history of venous thrombosis. The mutation results in a substitution of 82 Ser by Asn, creating a new glycosylation site. Expression studies were then carried out, to confirm Asn-linked glycosylation occurred at this consensus site and that this resulted in the AT deficient phenotype. Cell-free translations using rabbit reticulocyte lysate in the presence of microsomes demonstrated that the 82 Asn variant was post-translationally processed efficiently. The 82 Asn variant protein was of a higher molecular weight than normal AT, consistent with the addition of a fifth glycan chain. Incubation of translation product with endoglycosidase H, confirmed that the higher molecular weight product had resulted from additional carbohydrate. Expression of the 82 Asn variant in COS-7 cells resulted in intracellular accumulation, with a low level of secretion of the protein into culture supernatant, consistent with type I AT deficiency. The addition of an extra carbohydrate side chain to residue 82 of antithrombin may block post-translational folding, trapping the variant intracellulary.
The Role of Protein S in the Activation of Thrombin Activatable Fibrinolysis Inhibitor (TAFI) and Regulation of Fibrinolysis
Authors: Mosnier Laurent , Meijers Joost , Bouma Bonno 
Published: March 2018

SummaryThrombin activatable fibrinolysis inhibitor (TAFI) is a carboxypeptidase B-like proenzyme that after activation by thrombin downregulates fibrinolysis. Thrombomodulin stimulates the activation of both TAFI and protein C whereas activated protein C inhibits the activation of TAFI by downregulation of thrombin formation, a process in which protein S acts as a cofactor. Here we determined the role of protein S in the activation of TAFI and regulation of fibrinolysis. Depletion of protein S from plasma or inhibition of protein S by specific antibodies resulted in an increased rate of TAFI activation and in an increased maximum of TAFIa activity generated. The effect on the rate of TAFI activation could be attributed to the APC-independent anticoagulant function of protein S whereas the effect on the maximum activity could be attributed to the APC cofactor function of protein S. Therefore it is concluded that protein S inhibits TAFI activation in two ways. On one hand, protein S functions as a cofactor for APC which results in a reduction of the maximum induced TAFI activity and on the other hand protein S inhibits the initial thrombin formation independently of APC which results in a decreased rate of TAFI activation. The effect of the APC-independent anticoagulant activity of protein S on the activation of TAFI provides a new mechanism for the regulation of fibrinolysis in the early stages of clot formation.
A Hamster Antibody to the Mouse Fibrinogen Chain Inhibits Platelet-fibrinogen Interactions and FXIIIa-mediated Fibrin Cross-linking, and Facilitates Thrombolysis
Authors: JirouȈsková Markéta , Smyth Susan , Kudryk Bohdan , Coller Barry 
Published: March 2018

SummaryMurine models employing genetically altered mice have the potential to provide important new information about the hemostatic system, but before such data can be extrapolated to humans it is necessary to define the similarities and differences between murine and human hemostasis. After establishing the similarities of murine fibrinogen to human fibrinogen in its pattern of proteolysis in response to plasmin and its cross-linking by factor XIIIa, we studied a new hamster monoclonal antibody (mAb) 7E9 that reacts with the γ chain of mouse fibrinogen. This antibody inhibits platelet adhesion to fibrinogen, platelet-mediated clot retraction, platelet aggregation, and FXIIIa-mediated cross-linking of fibrin; it also facilitates tissue plasminogen activator (tPA)-mediated lysis of fibrin formed either in the absence or presence of platelets. These data provide evidence that the C-terminus of mouse fibrinogen γ chain, like that of human fibrinogen, is involved in fibrinogen binding to platelets and FXIIIa-mediated cross-linking of fibrin. Our data raise the possibility that a therapeutic agent that targets the C-terminus of the γ chain in human fibrinogen might have broad antithrombotic and profibrinolytic effects.
Alterations of Platelet Aggregation Kinetics with Ultraviolet Laser Emission: The “Stunned Platelet” Phenomenon
Authors: Minisi Anthony , Bernardo Nelson , McPherson Richard , Martin Erika , Carr Sheryl , Carr Marcus , Topaz On 
Published: March 2018

SummaryPlatelets, a major constituent of thrombus, play a crucial role in the pathogenesis of acute ischemic coronary syndromes. The effect of ultraviolet laser emission on platelets within thrombi is unknown. The effects of increasing levels of laser energy on platelets in whole blood were investigated. Blood samples were obtained by aseptic venipuncture and anticoagulated with 3.8% sodium citrate. Samples were exposed to increased levels (0, 30, 45, 60 mJ/mm2; 25 Hz) of ultraviolet excimer laser fluence (308 nm wave-length) and then tested for ADP and collagen induced platelet aggregation, platelet concentration, and for platelet contractile force (PCF) development. Scanning electron microscopy was used to detect laser induced morphologic changes of platelets and by flow cytometric analysis to detect changes in expression of platelet surface antigens p-selectin (CD 62) and glycoprotein IIb/IIIa (CD 43). Exposure to excimer laser energy produced dose dependent suppression of platelet aggregation and force development (“stunned platelets”). ADP aggregation decreased from 8.0 ± 1.1 Ohms (mean ± SEM) to 3.7 ± 0.8 Ohms (p 0.001) to 2.7 ± 0.6 Ohms (p 0.001) and to 1.8 ± 0.5 Ohms (p 0.001) as the laser energy increased from 0 to 30 to 45 to 60 mJ/mm2, respectively. Collagen induced aggregation decreased from 21.4 ± 1.4 Ohms to 15.7 ± 1.2 Ohms (p 0.001) to 11.7 ± 1.1 Ohms (p 0.001) and to 9.9 ± 1.0 Ohms (p 0.001), in response to the same incremental range of laser energy. Platelet contractile forces declined from 34,500 ± 3700 to 27,800 ± 2700 dynes as laser energy increased from 0 to 60 mJ/mm2 (p 0.03). Platelet concentration did not change with increasing laser energy. The expression of platelet surface antigen p-selectin (CD 62) remained stable through increasing levels of laser energy exposures while the percentage of CD 43 positive platelets significantly increased with exposure to laser energy, yet the level of expression did not exceed 0.5% of cells. Thus, aggregation kinetics are altered in platelets exposed to ultraviolet laser energy as manifested by decreased platelet aggregation and reduction in platelet force development capability. The response is dose dependent and most pronounced at higher energy levels such as 60 mJ/mm2.
Thrombin Induces Increased Expression and Secretion of VEGF from Human FS4 Fibroblasts, DU145 Prostate Cells and CHRF Megakaryocytes
Authors: Li J-J. , Hu L. , Lee M. , Karpatkin S. , Huang Y-Q. 
Published: March 2018

SummaryAngiogenesis is required for tumor growth and metastasis. It has recently been suggested that thrombin is a potent promoter of angio-genesis. We therefore examined the possibility that thrombin could be inducing the expression of vascular endothelial growth factor (VEGF), which promotes endothelial growth. Primary human FS4 fibroblasts as well as tumor cell lines: prostate DU145 and megakaryocyte CHRF were incubated with thrombin (0.25-1 unit/ml) for 1-8 hrs and then examined for mRNA by Northern Analysis. Enhanced mRNA (~3-4 fold over base line) was noted at 2-4 hrs, with 0.5 u/ml thrombin. The effect was specific for thrombin activity on its PAR-1 receptor, since equal units of hirudin completely inhibited the response and the thrombin effect could be mimicked with the 14 mer thrombin receptor activation peptide (TRAP). Upregulation of mRNA was associated with enhanced VEGF protein synthesis and secretion as assayed by immunoblot. Enhanced expression of VEGF mRNA was not secondary to enhanced transcription (nuclear run on experiments), but due to an >3 fold stabilization of mRNA (Actinomycin D chase experiment). Enhanced VEGF mRNA stabilization is promoted by the PI3Kinase and serine/threonine kinase pathways, since thrombin-induced mRNA expression is inhibited by Wortmanin and H7. No effect was noted with the MAPKinase inhibitor, PD98059. Thus, thrombin-induced tumori-genesis and metastasis is associated with enhanced VEGF protein synthesis and secretion via the stabilization of VEGF mRNA promoted by the PI3Kinase and serine/threonine kinase pathways. This could help explain how thrombin promotes angiogenesis.
Comparison of subchondral lesion size between clinical and non-clinical medial trochlear ridge talar osteochondritis dissecans in dogs
Authors: Van Ryssen B. , Coopman F. , van Bree H. , Gielen I. 
Published: March 2018

SummaryIn this retrospective study of nine dogs exhibiting bilateral medial trochlear ridge talar osteochondritis dissecans (MTRT-OCD) and unilateral hind limb lameness, we compared subchondral lesion size in limbs with visible lameness, with contralateral lesions that were not associated with any visible lameness. All MTRT-OCD lesions were imaged by radiography and computed tomography (CT). The dimensions of subchondral bone lesions were measured (length, width and depth) using CT software. Similar to a method used in humans, the estimated volume (length x width x depth) and cross sectional area (length x width) were calculated and compared. We found that MTRT-OCD lesions causing visible lameness were significantly larger, and were associated with more joint thickening and degenerative joint disease than contralateral lesions that were not associated with any apparent lameness. As in the disease of shoulder osteochondritis dissecans, there is probably a correlation between the size of MTRT-OCD lesions and the symptoms of lameness.
Optimization of corticosteroid induced osteoporosis in ovariectomized sheep
Authors: Schawalder P. , Rahn B. , Eckhardt C. , Schneider E. , Lill C. , Klopfenstein Bregger M. D. 
Published: March 2018

SummaryDuring osteoporosis induction in sheep, side effects of the steroids were observed in previous studies. The aim of this study was to improve the induction regimen consisting of ovariectomy, calcium/vitamin D- restricted diet and methylprednisolone (-MP)- medication with respect to the bone metabolism and to reduce the adverse side effects. Thirty-six ewes (age 6.5 ± 0.6 years) were divided into four MP-administration groups (n=9) with a total dose of 1800 mg MP: group 1: 20 mg/day, group 2: 60 mg/ every third day, group 3: 3x 500 mg and 1x 300 mg at intervals of three weeks, group 4: weekly administration, starting at 70 mg and weekly reduction by 10 mg. After double-labelling with Calcein Green and Xylenol Orange, bone biopsy specimens were taken from the iliac crest (IC) at the beginning and four weeks after the last MP injection, and additionally from the vertebral body (VB) at the end of the experiment. Bone samples were processed into stained and fluorescent sections, static and dynamic measurements were performed. There were no significant differences for static parameters between the groups initially. The bone perimeter and the bone area values were significantly higher in the VB than in the IC (Pm: 26%, p<0.0001, Ar: 11%, p<0.0166). A significant decrease (20%) of the bone area was observed after corticosteroid- induced osteoporosis (p<0.0004). For the dynamic parameters, no significant difference between the groups was found. Presence of Calcein Green and Xylenol Orange labels were noted in 50% of the biopsies in the IC, 100% in the VB. Group 3 showed the lowest prevalence of adverse side effects. The bone metabolism changes were observed in all four groups, and the VB bone metabolism was higher when compared to the IC. In conclusion, when using equal amounts of steroids adverse side effects can be reduced by decreasing the number of administrations without reducing the effect regarding corticosteroid- induced osteoporosis. This information is useful to reduce the discomfort of the animals in this sheep model of corticosteroid-induced osteoporosis.
Femoroazetabuläres Impingement
Authors: Messler J. , Seller M. , Rüther W. , Seitz S. 
Published: March 2018

ZusammenfassungDas femoroazetabuläre Impingement (FAI) ist als ein Engesyndrom am Hüftgelenk definiert, das durch einen abnormalen Kontakt zwischen vorderem Pfannenrand und dem Übergang Hüftkopf/Schenkelhals entsteht und vor allem bei jungen Erwachsenen auftritt. Abhängig von der Lokalisation der auftretenden Pathologie wird zwischen einem azetabulären Pince- rund einem femoralen Cam-Impingement unterschieden, wobei in der Mehrzahl der Fälle eine Kombination aus beiden besteht. Die Diagnostik beruht neben einem klinisch schleichenden Beschwerde - beginn und typischer Schmerzauslösung bei Adduktion und Innenrotation auf konventionell radiologischen und ergänzenden MR-tomografischen Aufnahmen. Die einzige kausale Therapie des femoroazetabulären Impingements besteht in der Behebung der mechanischen Enge mit dem Ziel, die Hüft - anomalie möglichst zu normalisieren, um die Arthroseentwicklung bei den meist jungen Erwachsenen zu vermeiden. Eine operative Therapie sollte daher frühzeitig eingeleitet werden. Dabei stellen heutzutage minimalinvasive und arthroskopische Techniken mit guten mittelfristigen Ergebnissen eine sehr gute Alternative zur chirurgischen Luxation dar.