bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Concentrations of Soluble CD40 Ligand, RANTES and GRO-α in Preeclampsia – Possible Role of Platelet Activation
Authors: Solum Nils Olav , Ueland Thor , Videm Vibeke , Aukrust Pål , Mellembakken Jan Roar 
Published: March 2018

SummaryActivated platelets may release inflammatory mediators that activate leukocytes and trigger inflammatory reactions in endothelial cells. We examined the concentrations of soluble CD40 ligand (sCD40L) and the chemokines RANTES and GRO-α in platelet-free plasma (PFP), and unstimulated and SFLLRN-stimulated platelet-rich plasma (PRP), as well as in platelet pellets before stimulation using enzyme immunoassays. Nineteen women with normal and twenty-one with preeclamptic pregnancies were studied, and several differences between these two groups of pregnancies were revealed (1). Women with preeclampsia had significantly increased concentrations of sCD40L and GRO-α in PFP (2). Platelets from these patients spontaneously released larger quantities of CD40L and RANTES ex vivo (3). When further activated ex vivo by SFLLRN, platelets from preeclamptic women released lower amounts per platelet of CD40L, RANTES and GRO-α (4). The platelet pellets in preeclamptic women contained decreased amounts of CD40L, RANTES and GRO-α per platelet. Our findings suggest enhanced platelet activation in vivo during preeclampsia resulting in increased release of inflammatory mediators, possibly contributing to inflammation, leukocyte activation and endothelial dysfunction in this disorder.
A Novel Transgenic Mouse Model of Hyperfibrinogenemia
Authors: Gulledge Alyssa , Rezaee Farhad , Verheijen Jan , Lord Susan 
Published: March 2018

SummaryHyperfibrinogenemia is a risk predictor in several diseases, including cardiovascular disease. Nevertheless, it remains unknown whether elevated fibrinogen has an etiologic role in or is a reflection of disease pathogenesis, or both. To examine this question, we generated a mouse model of hyperfibrinogenemia. We isolated the mouse fibrinogen locus, containing the three fibrinogen genes, in a single P1 clone. This ~ 100 kb clone was injected into C57Bl/6J zygotes. Three transgenic lines were identified, two with elevated fibrinogen, 1.4- and 1.7-fold relative to normal. We characterized the line with the higher level. Northern blots of total RNA showed transgene expression was liver specific, and the message levels were 2- to 3-fold enhanced. Fibrinogen in transgenic mice was normal in both immunologic and clotting assays. Our data indicate that over-expression of all three fibrinogen genes is necessary to achieve hyperfibrinogenemia. We saw no increase in mortality or morbidity, no gross abnormalities in the organs, and no histologic differences in lung, liver, spleen or kidney, in transgenic mice relative to normal littermates. We conclude that elevated fibrinogen did not cause disease in mice. We anticipate that breeding these mice to other mouse models of disease will demonstrate whether hyper-fibrinogenemia has a role in the initiation or progression of symptomatic disease.
Anticardiolipin Antibody Assay: a Methodological Analysis for a better Consensus in Routine Determinations
Authors: Allegri Flavio , Sanmarco Marielle , Cinquini Massimo , Taglietti Marco , Balestrieri Genesio , Koike Takao , Ichikawa Kenji , Meroni Pierluigi , Boffa Marie Claire , Tincani Angela 
Published: March 2018

SummaryDespite the widely recognized practical importance of anticardiolipin (aCL) ELISA, the reliability of this test has been recently discussed. In order to investigate this area on European scale, we sent to 30 experienced centers a questionnaire focusing on the diagnostic procedures applied to patients with antiphospholipid syndrome (APS) and on the detailed protocols used to perform aCL. Anticardiolipin ELISA was found to be the most frequently performed test in patients with suspected APS, but significant difference was shown among the various protocols. The cross-laboratory multiple examination of ten serum samples evaluated independently by the 24 centers pointed out the difficulty in getting comparable results. Therefore a “consensus” protocol was derived from the aCL methods giving the best performance. The materials and reagents necessary to perform the “consensus” method, including, as putative standards, one IgG and one IgM monoclonal antibody (HCAL and EY2C9) were distributed to 19 Centers. The results of one IgG and one IgM aCL high positive sera measured in serial dilutions were compared. A progressive decrease in the variability of the values obtained for a given sample appeared evident when all the laboratories used the same standard, in their own in-house ELISA and even more in the “consensus” ELISA.Our data show that aCL ELISA standardization is necessary in order to obtain comparable results in different laboratories.
β2-glycoprotein I-dependent Anticardiolipin Antibodies Preferentially Bind the Amino Terminal Domain of β2-glycoprotein I
Authors: McNeeley Patricia , Dlott Jeffrey , Furie Richard , Jack Richard , Triplett Douglas , Victoria Edward , Ortel Thomas , Linnik Matthew 
Published: March 2018

SummaryMany of the autoantibodies in antiphospholipid syndrome (APS) are directed against β2-glycoprotein I (β2-GPI). Recent studies from our laboratories have indicated that the immunodominant binding epitope(s) for high titer, affinity purified antibodies from 11 APS patients are localized to the amino terminal domain (domain 1) of β2-GPI. The present study employed surface plasmon resonance to localize the immunodominant domain in serum samples from a large cohort of patients with GPL values ranging from 21 to 230 units (n = 106 patients). Eighty-eight percent of patients showed ≥ threefold selectivity for β2-GPI containing domain 1 relative to the domain deletion mutant that lacked domain 1. The domain 1 binding activity in patient serum was abolished by removing the IgG fraction from the serum and the binding activity could be fully reconstituted with the IgG fraction. Thus, analysis of serum samples from a large cohort of APS patients indicates that the immunodominant binding epitope(s) for anti- 2 antibodies are localized to the amino terminal domain of β2-GPI.
Effect of Melagatran on Prothrombin Time Assays Depends on the Sensitivity of the Thromboplastin and the Final Dilution of the Plasma Sample
Authors: Menschiek-Lundin Angela , Wåhlander Karin , Lindahl Tomas , Mattsson Christer 
Published: March 2018

SummaryProthrombin time (PT) assays are clotting methods that measure the activity of vitamin K-dependent coagulation factors (F) II, VII, and X. There are three main types of PT assays in general usage, namely the Quick assay, Owren’s assay and PT dry chemistry test cards. PT assays were initially developed to monitor dose-adjustments of vitamin K antagonists such as warfarin. The aim of the present study was to investigate whether commercially available PT assays are suitable for evaluating the anticoagulant activity of direct thrombin inhibitors. Melagatran, a reversible direct thrombin inhibitor, was added to human plasma at concentrations ranging from 0.1 to 2.0 μmol/l. Seventeen different commercially available PT kits were used, including thirteen Quick reagents, two Owren reagents and two PT test cards. The sensitivity of the different reagents, expressed as the concentration of melagatran that doubled the prothrombin time (IC50) varied widely, with Thromboplastin S and Thromboplastin HS being the most sensitive (IC50 = 0.9 μmol/l). The reagents with apparently the lowest sensitivity were the two Owren reagents Nycotest PT and SPA 50 with an IC50 of 2.2 and 2.9 μmol/L, respectively. This is most likely due to a higher dilution of melagatran in these assays compared to the dilution in the Quick assays. The results were also dependent on the International Sensitivity Index (ISI) of each reagent. The concentration of melagatran that produced an International Normalized Ratio (INR) of 2 was calculated from dose-response curves for each assay, and these results revealed that reagents with a high ISI value gave an INR of 2 at much lower concentrations of melagatran (0.5-0.7 μmol/L) than those with an ISI-values around one (0.9-1.2 μmol/L). It was found that INR depends not only on the plasma concentration of melagatran, but also on the sensitivity of the PT reagent and on the final dilution of the plasma sample in the prothrombin time assay. Thus, since the same melagatran concentration can be associated with widely varying PT/INR results depending on the specific assay used it is concluded that PT assays and INR can not be used to monitor melagatran activity.
Expression of Protein S in the Murine Heart and Cultured Mouse Cardiomyocytes Is Down-regulated by Cytokines
Authors: Shimokawa Takayoshi , Yamafuji Eriko , Kojima Tetsuhito , Saito Hidehiko , Yamamoto Koji 
Published: March 2018

SummaryProtein S (PS), a co-factor of activated protein C, is a vitamin K-dependent anticoagulant protein and is known to be produced extrahepatically. In the present study, the concentration of PS mRNA was determined tissue by tissue in the mouse, and it was high in lung, adrenal and heart as well as in liver. We further investigated the effects of lipopolysaccharide (LPS), tumor necrosis factor-α (TNF-α), and interleukin-1 (IL-1) on the PS mRNA expression in murine tissues in vivo. Although LPS and TNF-α significantly decreased the expression level of PS mRNA in all tissues examined (e.g., lung, liver, heart, and kidney) and the PS antigen level in plasma, the suppressive effect of IL-1 on PS gene expression was limited to heart. More specifically, considerable amounts of PS mRNA and antigen were expressed in a cultured mouse cardiomyocyte cell line, and again, treatment with IL-1 decreased the PS expression in these cells. These observations raise a possibility that the expression of cardiac PS may contribute to the regional anticoagulant potential in heart, and suggest that the decreased PS expression by cytokines may result in an increase in the systemic and/or regional prothrombotic potential under inflammatory conditions.
Platelets and Phospholipids in Tissue Factor-initiated Thrombin Generation
Authors: Butenas Saulius , Branda Richard , van ’t Veer Cornelis , Cawthern Kevin , Mann Kenneth 
Published: March 2018

SummaryThe influence of platelets on tissue factor (TF)-initiated thrombin generation in a reconstituted model of blood coagulation and in whole blood was evaluated. No thrombin generation was observed over 15 min in the reconstituted model when either TF or platelets and phospholipids were omitted. At 25 pM TF, the rates of thrombin generation were platelet and PCPS concentration-dependent and achieved maximum (1.0 nM/s) in the physiological range of platelet concentration. Similar rates were achieved in the absence of platelets when 1-2 μM phospholipid was used. However, the maximum rates of thrombin generation (5.2-6.0 nM/s) and the shortest initiation phase (1 min) were attained between 25 and 100 μM phospholipid. In the reconstituted model, an increase in platelet concentration from 0.125 × 108/ml to 0.5 × 108/ml decreased the duration of the initiation phase (in the absence of phospholipids) from 4.3 min to 2 min. Further increases in platelet concentration did not affect this phase. Sequential whole blood studies were conducted in blood of a chemotherapy patient who developed reduced platelet counts. The TF (12.5 pM) initiated clotting of patient’s blood was accelerated from ~10 min to 5 min when the platelet concentration increased from 0.05 × 108/ml to 0.11 × 108/ml. Clotting times were essentially unchanged for platelet concentrations exceeding 0.5 × 108/ml (range 0.5-3.1 × 108/ml). Similarly, clotting of whole blood obtained from healthy volunteers was not affected by the platelet count, which varied from 1.5 × 108/ml to 3.1 × 108/ml (4.0 ± 0.5 min). The data obtained in both models are consistent with in vivo observations that clinical bleeding is most likely to occur at platelet counts <0.1 × 108/ml.Portions of this work were presented at the 40th Annual Meeting of the American Society of Hematology, December 4-8, 1998, Miami Beach, Florida (abstracts #140 and #738).
Antithrombotic Strategy in Stroke
Authors: Bousser Marie-Germaine 
Published: March 2018

SummaryNumerous randomised controlled trials have been devoted to antithrombotic strategy in stroke, thus making evidence-based recommendations possible. The use of antithrombotic drugs is crucial in the treatment of ischemic stroke though often limited by the inherent risk of intra-cerebral bleeding. In the prevention of stroke, the strategy depends on the underlying etiology: (i) antiplatelet drugs (with aspirin as first choice) in atherothrombotic stroke, and (ii) oral anticoagulants in cardioembolic stroke. In the acute treatment, the strategy depends on whether IV rt-PA can be performed; if rt-PA is available and approved, its use is recommended within 3 h of the onset of symptoms provided there is strict adherence to the inclusion and exclusion criteria. In all other cases, aspirin is the treatment of choice, associated with low dose LMWH in the event of restricted mobility. There is no evidence for efficacy of high dose heparin (or LMWH) in stroke, except in cerebral venous thrombosis.
Genetic Interactions between the Coagulation and Fibrinolytic Systems
Authors: Degen Jay 
Published: March 2018

SummaryNearly all of the genes encoding the established coagulation and fibrinolytic factors have been successfully altered or disrupted in transgenic mice. Although comprehensive studies of each of these genetargeted mouse lines are still ongoing, the initial findings have significantly refined our understanding of the roles of selected hemostatic factors in vivo, and occasionally altered long-standing concepts. This review summarizes some of the progress that has been made in the generation and phenotypic characterization of mice lacking key hemostatic factors, including coagulation, fibrinolytic, platelet and endothelial cell-associated factors. New insights regarding the role(s) and interplay of hemostatic factors that have emerged from detailed studies of mice carrying multiple deficits in coagulation and fibrinolytic system components are highlighted.
Tissue Plasminogen Activator in Nervous System Function and Dysfunction
Authors: Strickland Sidney 
Published: March 2018

SummaryThe extracellular protease tissue plasminogen activator (tPA) has been implicated in various normal and pathological situations in the mammalian nervous system. The availability of (i) transgenic and knock-out mice in which the expression level of tPA can be widely varied, (ii) in vivo models for studying function and disease, and (iii) culture models for examining cell behavior, has allowed a detailed evaluation of many of these proposed functions. This chapter summarizes the current state of knowledge of possible roles for the tPA/plasminogen system in neuronal function and dysfunction.
Cost-effective Diagnosis of Deep Vein Thrombosis and Pulmonary Embolism
Authors: Bounameaux Henri , Perrier Arnaud 
Published: March 2018

SummarySuspected acute venous thromboembolism is a frequent and challenging clinical problem. Phlebography and pulmonary angiography are costly and invasive and, hence, ill-suited for diagnosing a disease present in only 20% of patients in whom it is suspected. Novel noninvasive instruments, such as plasma D-dimer measurement, lower limb compression ultrasonography and helical CT scan are important breakthroughs in the management of patients with suspected venous thromboembolism. However, none of these instruments is ideal, and they must be combined in rational and cost-effective diagnostic algorithms including clinical assessment, which is increasingly standardized. Such strategies must be validated in management studies, in which patients without venous thromboembolism are not treated and followed up during 3 months. Suspected massive pulmonary embolism is a distinct clinical situation requiring a specific diagnostic approach, in which echocardiography plays a major role. This paper reviews the performance of clinical evaluation and diagnostic tests for venous thromboembolism, and recently validated diagnostic schemes.
Heparins and Venous Thromboembolism: Current Practice and Future Directions
Authors: Prandoni Paolo 
Published: March 2018

SummaryUnfractionated heparin (UFH) in adjusted doses and low-molecularweight heparins (LMWH) in fixed doses are the chosen therapy for the initial treatment of venous thromboembolism. The use of UFH protocols ensures that virtually all patients will promptly achieve the therapeutic range for the activated partial thromboplastin time. However, proper use of UFH requires considerable expertise, can cause inconvenience and has limitations. Unmonitored therapy with subcutaneous LMWH is at least as effective and safe as adjusted-dose UFH, is associated with a considerable reduction of mortality in cancer patients, and permits the treatment of suitable patients in an outpatient setting.LMWH in high prophylactic doses is more effective than UFH and oral anticoagulants for prevention of postoperative venous thrombosis in major orthopedic surgery. Whether thromboprophylaxis should be continued for a few additional weeks after hospital discharge is controversial. LMWH and UFH are equally effective for prevention of postoperative deep-vein thrombosis in cancer patients. In a recent controlled randomized trial, enoxaparin in high prophylactic doses was an effective and safe measure of thromboprophylaxis in ordinary bedridden patients.The efficacy and safety of pentasaccharide (the smallest antithrombin binding sequence of heparin) in the treatment and prevention of venous thromboembolic disorders is currently under investigation.
Zöliakie – keine Beschwerden und doch lebenslange Diät?!
Authors: Wimmer K. 
Published: March 2018

ZusammenfassungDie Therapie bei der Zöliakie besteht aus einer lebenslangen glutenfreien Ernährung, bei der die einheimischen Getreide und Getreideprodukte aus Weizen, Roggen und Gerste strikt gemieden werden müssen. Die Verwendung von sortenreinem Hafer im Rahmen der glutenfreien Diät wurde mit dem Erlass der S2k-Leitlinie Zöliakie geregelt, sollte aber für Kinder und Jugendliche aufmerksam betrachtet werden. Durch eine steigende Vielzahl von glutenfreien Diätprodukten und die Aufstellung glutenfreier, nicht diätetischer Lebensmittel der Deutschen Zöliakie-Gesellschaft e. V. (DZG) können Zöliakiebetroffene sich trotz Diät ausgewogen, abwechslungsreich und bedarfsdeckend ernähren.Mit der neuen Lebensmittelinformationsverordnung der EU (LMIV) vom 13. Dezember 2014 werden die Lebensperspektiven nochmals verbessert, da eine Kennzeichnung von Gluten für alle Lebensmittel Pflicht ist.
Strategien des Robert Koch-Instituts zum Monitoring der Gesundheit von in Deutschland lebenden Kindern und Jugendlichen
Authors: Kamtsiuris P. , Hölling H. , Mauz E. , Kurth B.-M. 
Published: March 2018

ZusammenfassungDas Robert Koch-Institut (RKI) als deutsches Public Health-Institut zählt zu seinen vornehmlichen Aufgaben das Monitoring der Gesundheit der in Deutschland lebenden Bevölkerung. Kinder und Jugendliche stellen dabei als vulnerable Gruppe einen besonderen Schwerpunkt dar. Die Arbeit beschreibt die Konzepte und Strategien des Instituts, um durch das Gesundheitsmonitoring für Kinder und Jugendliche Informationen zur gesundheitlichen Versorgung, zum Gesundheitsverhalten und dem Gesundheitszustand der jungen Generation in Deutschland zu sammeln. Ziel ist die Identifizierung von Handlungsbedarfen und die Evaluation Public Health-relevanter Maßnahmen. Dem Ganzen liegt der Gedanke der Vernetzung mit allen auf dem Gebiet der Kindergesundheit tätigen Akteuren zugrunde und manifestiert sich in der adressatengerechten Aufbereitung und Bereitstellung der erhobenen Daten.
Interdisziplinäre Versorgung in den Sozialpädiatrischen Zentren in Deutschland
Authors: Kretzschmar C. , Babitsch B. , Pöche-Guckelberger I. 
Published: March 2018

Zusammenfassung‚Neue Morbiditäten‘ mit ihren multifaktoriellen Ursachen erfordern eine komplexe interdisziplinäre Versorgung. Ein Vergleich der SPZ-Versorgung in Deutschland in 2006 und 2011 zeigte einen Anstieg der Quartalsüberweisungsscheine um 51 %. In beiden Jahren waren Kindergartenkinder im Alter von drei bis knapp sechs Jahren und Grundschüler die größten Patientengruppen. In 2011 waren Entwicklungsstörungen sowie Verhaltens- und emotionale Störungen die am häufigsten gestellten Diagnosen. Die Anzahl der Ärzte/innen und Psychologen/-innen ist im Vergleich von 2006 zu 2011 gestiegen, wohingegen die Anzahl der therapeutischen Mitarbeiter/-innen (Physiotherapie, Ergotherapie und Logopädie) sowie die der Heil- und Sozialpädagogen/-innen nahezu gleich blieb. Der Anstieg bei den Scheinen lässt auf einen erhöhten Versorgungsbedarf bei Kindern und Jugendlichen schließen. Ursachen für diesen Trend könnten in den veränderten Umgebungsbedingungen und vielfach schwierigen psychosozialen Lagen liegen. Um dem Bedarf von Kindern und Jugendlichen mit komplexen Krankheitsbildern gerecht werden zu können, sollten jedoch die therapeutischen Professionen sowie die der Heil- und Sozialpädagogen/innen stärker in den SPZ vertreten sein.
Schilddrüsenknoten im Kindes- und Jugendalter
Authors: Hennes P. , Schiller M. , Jung A.-M. , Rohrer T. R. 
Published: March 2018

ZusammenfassungSchilddrüsenknoten sind im Kindes- und Jugendalter deutlich seltener als bei Erwachsenen. Je nach Untersuchungsmethode und Population liegt ihre Häufigkeit bei pädiatrischen Patienten bei 0,7–1,8 %. Die Rate korrekt erfasster Malignome beträgt zwischen 0,5 % der entdeckten Knoten in sonografischen Screening-Untersuchungen an gesunden Kindern bis hin zu 25 % bei Beschränkung auf Patienten mit spezifischen Ultraschallkriterien für ein Malignom.Die Sonografie spielt als wichtigste bildgebende Diagnostik bei Schilddrüsenveränderungen eine entscheidende Rolle. Neben Laboranalyse und klinischer Untersuchung ist die korrekte Einordnung der Ultraschallbefunde von zentraler Bedeutung. Sowohl in der internistischen als auch der pädiatrischen Endokrinologie und Ultraschalldiagnostik führt eine strukturierte, standardisierte Befunderhebung zu einer besseren Auswahl von Patienten für Feinnadelpunktionen. Neuere technische Verfahren, wie die Elastografie sind ein hilfreiches Instrument, um die Patienten für eine ultraschallgesteuerte Feinnadelpunktion auszuwählen und anhand dieser Befunde die Entscheidung zu einer Operationsindikation fundiert stellen zu können.
Bedeutung der Genetik in der Kindernephrologie
Authors: Hoefele J. 
Published: March 2018

ZusammenfassungBei vielen kindernephrologischen Erkrankungen ist heutzutage eine genetische Ursache bekannt. Unter Verwendung neuester Technologien in der Humangenetik können diese Erkrankungen frühzeitig diagnostiziert, invasive klinisch-diagnostische Eingriffe bei diesen Patienten ggf. vermieden, mögliche Komplikationen der Erkrankungen durch entsprechende Therapie verhindert oder hinausgezögert und Kosten für die Therapien signifikant reduziert werden. Die molekulargenetische Untersuchung wird in den kommenden Jahren einen zunehmenden Stellenwert in der Kindernephrologie einnehmen. Im Folgenden wird ein Überblick über genetische Aspekte wesentlicher Erkrankungen in der Kindernephrologie sowie über empfohlene Untersuchungstechniken gegeben.