bluuebunny/crossref_metadata_2025_split huggingface dataset:
Einfluss der Atmungstherapie auf die Inzidenz von nosokomialen Pneumonien in der neurologisch-neurochirurgischen Frührehabilitation: Ergebnisse einer Fall-Kontroll-Analyse
Authors: Schmidt Simone Bianca , Boltzmann Melanie , Rollnik Jens Dieter 
Published: July 2018

Zusammenfassung
Hintergrund In der neurologisch-neurochirurgischen Frührehabilitation (NNFR) gehen viele Krankheitsbilder mit einem erhöhten Risiko von Pneumonien einher. Vor einigen Jahren wurde die Disziplin der Atmungstherapie etabliert, um respiratorische Komplikationen abzuwenden. Derzeit gibt es allerdings keine Studien, die die Effektivität der Atmungstherapie im Hinblick auf die Inzidenz von Pneumonien in der NNFR belegen könnten.
Methode In die Studie wurden 81 Phase-B-Patienten, die während ihres Aufenthaltes eine Atmungstherapie erhalten haben, und 81 Kontrollpatienten eingeschlossen. Routinemäßig erhobene Daten wie Alter, Geschlecht, Diagnosen, Komorbiditäten, Behandlungsdauer sowie Informationen zum Beatmungsstatus und der Entstehung von Pneumonien wurden retrospektiv analysiert.
Ergebnisse Die Entstehung einer Pneumonie war mit einer längeren Behandlungsdauer, einer höheren Anzahl an Beatmungsstunden, dem Vorhandensein einer Trachealkanüle und einem tendenziell niedrigerem Frühreha-Barthel-Index bei Aufnahme assoziiert. Die Inzidenzrate nosokomialer Pneumonien lag in beiden Studiengruppen bei 20%. Die Gruppen unterschieden sich signifikant in der Krankheitsschwere bei Aufnahme, der Behandlungsdauer, der Anzahl an Dysphagie-Patienten sowie in den Therapieintensitäten der Physio-und Sprachtherapie.
Schlussfolgerung Ein direkter Zusammenhang zwischen der Atmungstherapieintensität und der Pneumonieinzidenz in der NNFR konnte aufgrund der unzureichenden Vergleichbarkeit beider Studiengruppen nicht abschließend nachgewiesen werden. Die Intensität der Dysphagie-Therapie war neben der Beatmungsdauer der stärkste die Pneumonieinzidenz beeinflussende Faktor.
Application of Metathesis Reactions in the Synthesis and Transformations of Functionalized β-Amino Acid Derivatives
Authors: Kiss Loránd , Kardos Márton , Vass Csaba , Fülöp Ferenc 
Published: July 2018

Because of their biological relevance, cyclic β-amino acids have generated increasing interest and had significant impact in drug research over the past two decades. Their preparation and further functionalization towards new types of molecular entities have received large interest in synthetic and medicinal chemistry. Various types of metathesis reactions, such as ring-opening (ROM), ring-closing (RCM), or cross metathesis (CM) are used widely for access to either alicyclic β-amino acids or other densely functionalized derivatives of this group of compounds. This account intends to provide an insight into the most relevant synthetic routes to this class of derivatives with the application of metathesis reactions. The review focuses on the presentation of selective and stereocontrolled methodologies in view of versatility, robustness, limitations and efficiency.1	Introduction2	Synthesis and Transformation of Cyclic β-Amino Acids through
Metathesis Reactions2.1	Synthesis of Five- and Six-Membered Cyclic β-Amino Acids by
Ring-Closing Metathesis2.2	Synthesis of Five- and Six-Membered Cyclic β-Amino Acids by
Cross Metathesis2.3	Synthesis of β-Amino Acids with Larger Ring Systems by Ring-
Closing Metathesis2.4	Synthesis of β-Amino Acids with Condensed Ring Systems by
Ring-Rearrangement Metathesis2.5	Stereocontrolled One-Step Synthesis of Functionalized Cispentacin
and Transpentacin Derivatives2.5.1 Stereocontrolled Synthesis of Functionalized Cispentacin and
Transpentacin Derivatives through Ring-Opening Metathesis of
Norbornene β-Amino Acid Derivatives2.5.2 Stereocontrolled Synthesis of Functionalized Azetidinones and
β-Amino Acid Derivatives from Condensed Ring β-Lactams by
Ring-Opening Metathesis2.5.3 Carbon–Carbon Double Bond Functionalization of β-Amino Acid
Derivatives and β-Lactams with α,β-Unsaturated Carbonyl	Compounds through Cross Metathesis2.5.4 Synthesis of Functionalized β-Amino Acid Derivatives and	β-Lactams through Chemoselective Cross Metathesis3	Conclusions and Outlook
Development of Novel C–H Bond Transformations and Their Application to the Synthesis of Organic Functional Molecules
Authors: Kuninobu Yoichiro 
Published: July 2018

This personal account summarizes our recent progress in the development of C–H transformations. We achieved ortho-selective C–H borylations and silylations by using Lewis acid–base interaction between two substrates and we achieved meta- and ortho-selective C–H borylations by using hydrogen bonding or Lewis acid–base interaction between a hydrogen donor or Lewis acid unit of a ligand and a functional group of a substrate. Regioselective C–H trifluoromethylations and related reactions of six-membered heteroaromatic compounds were realized at their 2- and 4-positions and at their benzylic positions. In addition, we developed C–H transformations directed towards the synthesis of organic functional materials, such as highly soluble polyimides or π-conjugated molecules containing either heteroatom(s) or a Lewis acid–base interaction.1	Introduction2	Regioselective C–H Transformations Controlled by Noncovalent Bond Interactions2.1	Regioselective C–H Transformations Controlled by Lewis Acid–Base Interaction between Two Substrates2.2	Regioselective C–H Transformation Controlled by Hydrogen Bonding between Ligand and Substrate2.3	Regioselective C–H Transformations Controlled by Lewis Acid–Base Interactions between Ligands and Substrates3	Trifluoromethylation and Related Transformations of Six-Membered Heteroaromatic Compounds3.1	2-Position-Selective C–H Trifluoromethylation of Six-Membered Heteroaromatic Compounds3.2	4-Position-Selective C–H Trifluoromethylation of Six-Membered Heteroaromatic Compounds3.3	Benzyl Position-Selective C–H Trifluoromethylation of Six-Membered Heteroaromatic Compounds4	C–H Transformations Leading to the Synthesis of Organic Functional Materials4.1	Heteroatom-Containing π-Conjugated Molecules4.2	π-Conjugated Molecules Containing a Lewis Acid–Base Interaction4.3	Soluble Polyimide Derivatives5	Conclusions
Thrombotic Risk of Women with Hereditary Antithrombin III-, Protein C- and Protein S-Deficiency Taking Oral Contraceptive Medication
Authors: Pabinger Ingrid , Schneider Barbara , Scharrer I , Hach-Wunderle V , Lechner K , Eichinger S , Kyrle P A , Vinazzer H , Lämmle B , Demarmels-Biasiutti F , Tilsner V , Marx G , Scifricd E , Gabelmann A , Aspöck G , Fischer M , Halbmaycr W M ,   The GTH Study Group on Natural Inhibitors,   GTH (Gesellschaft für Thrombose- und Hämostaseforschung) Study Group on Natural Inhibitors:
Published: July 2018

SummaryThe thrombotic risk of women with a heterozygous natural clotting inhibitor deficiency taking oral contraceptives (OC) has not been evaluated. Therefore, a retrospective collaborative controlled cohort-study was carried out in 8 coagulation laboratories and thrombosis units in Austria, Germany and Switzerland.The incidence of thromboembolism in 48 females heterozygous for hereditary type I deficiency of antithrombin ITT (n = 1.5), protein C. (n = 16) or protein S (n = 17), who had taken OC at least once in their life were compared with that of 48 deficient women, who had never taken OC (controls). Diagnosis of the deficiency state was made in the participating centers. Data on the onset and duration of OC intake and the date and site of thrombotic events were obtained from a questionnaire filled in by the patient or a physician during a visit at a participating center. The observation period in the OC patients was started with onset of OC intake and was terminated when a thromboembolic event had occurred or when OC medication were discontinued. In the patients without OC, the observation period began at an age matched to that of the OC patient and ended when a thromboembolic event had occurred or was continued as long as the corresponding OC patient was on treatment.In AT Ill-deficient females the probability for thrombosis was significantly higher for patients taking OC compared to the non-OC-patients (Wilcoxon test p = 0.004, Log Rank test p = 0.005). In patients with protein C- ((3-error 0.8) and protein S-deficiency ((3-error 0.05) there was no significant difference between the OC- and non-OC-group. The incidence of thrombosis/patient year in AT III-, PC- and PS-deficient females on OC was 27.5%, 12% and 6.5%, respectively and 3.4%, 6.9% and 8.6%, respectively, in the control patients.We conclude that females with hereditary antithrombin Ill-deficiency are at high risk for venous thromboembolism when taking OC. Therefore, OC should be strictly avoided in these females and AT III measurement is mandatory in female relatives of AT Ill-deficient patients at young age before starting OC. There is no evidence for an excess thrombotic risk by OC intake in PS-deficient females. In protein C-deficient women OC medication was not associated with a significant increase of thrombosis, but an increased risk cannot be excluded.
Heparin-Associated Thrombocytopenia: The Effects of Various Intravenous lgG Preparations on Antibody Mediated Platelet Activation - A Possible New Indication for High Dose i.v. IgG
Authors: Greinacher A , Liebenhoff U , Kiefel V , Presek P , Mueller-Eckhardt C 
Published: July 2018

SummaryThe immunologic type of heparin-associated thrombocytopenia (HAT) is caused by antibodies which activate platelets via the Fc-re- ceptor in the presence of polysulfated oligosaccharides. The antigen is formed by a releasable platelet protein (in many cases PF4) complexed to heparin. Since the role of GP Ilb/IIIa in platelet activation by HAT antibodies is controversial, we investigated platelet activation by antibodies related to HAT. We used normal platelets and platelets from a patient with Glanzmann’s thrombasthenia (GT) lacking GP Ilb/IIIa. Heparin and sera from patients with HAT stimulated GT platelets in the same manner as determined by 14C-serotonin release and the changes in phosphorylation of p20 and p47. Platelet activation could be inhibited by an anti FcRII monoclonal antibody (IV. 3, Fab-fragments), and by Fc-fragments, but not by F(ab’)2-fragments of human IgG. The effect of four different, commercially available preparations of intact i.v. IgG on the platelet activation by six HAT sera was investigated by 14C-seroto- nin release. The inhibitory effect was strongly dependent upon the manufacturing process. At a concentration of 20 mg/ml only IgG that had been subjected to low pH and traces of pepsin sufficiently inhibited platelet activation. IgG treated with polyethylenglycol or sulfitolysis was less effective, whereas beta-propiolactone-treated IgG almost completely lost the ability to inhibit platelet activation by antibodies related to HAT. We conclude that inhibition of GP Ilb/IIIa-fibrinogen interaction is insufficient for preventing platelet activation in HAT. This is, however, possible by high dose i.v. IgG, whereby inhibition of FcRII on platelets strongly depends upon the process by which the i.v. IgG preparation was manufactured.
A Collaborative Study to Establish the 2nd International Standard for Tissue Plasminogen Activator (t-PA)
Authors: Gaffney P J , Curtis A D 
Published: July 2018

SummaryAn international collaborative study involving ten laboratories located in eight different countries was undertaken in order to replace the current International Standard (I.S.) for tissue plasminogen activator (t-PA). Two lyophilised candidate preparations of high purity were assessed in comparison with the current I.S. for t-PA using only a clot lysis assay. One preparation (coded 861670) was purified from a cultured melanoma cell supernatant and was about 98% single chain t-PA while the other preparation (coded 861624) was derived from Chinese hamster ovary (CHO) cells following DNA recombinant procedures and was 75% single chain t-PA.Both candidate preparations of t-PA compared in quite a satisfactory manner with the current I.S. from the viewpoint of the biometrics of parallel line bioassays and both preparations were quite stable for long periods at low temperatures and stable from up to 1 month at temperatures of 20° and 38° C. Both fultil the criteria to serve as a satisfactory Znd International Standard for t-PA. The Fibrinolysis Subcommittee of the International Committee for Thrombosis and Haemostasis recommended the melanoma source t-PA (861670) as the next I.S. in order to maintain continuity with the 1st I.S. which was also a melanomatype preparation. The data from the ten laboratories indicated that each ampoule of the new proposed standard contains 850 international units of t-PA activity by the clot lysis assay. It is planned to present the results of this study to the Expert Committee on Biological Standardization of the World Health Organization at its next meeting and to request that the preparation of t-PA, coded 861670, be established as the 2ndlnternational Standard for t-PA.
Hemostasis in Patients Undergoing Extracorporeal Circulation: The Effect of Aprotinin (Trasylol)
Authors: Lu He , Soria Claudine , Commin Pierre-Louis , Soria Jeannette , Piwnica Armand , Schumann Friedrich , Regnier Odile , Legrand Yves , Caen Jacques Philippe 
Published: July 2018

SummaryThe administration of aprotinin during extracorporeal circulation (ECC) reduces blood loss. To explore the mechanism of this effect, a placebo-controlled double-blind study was performed in 20 patients (10 were administered with a high dose of aprotinin, 10 with placebo) undergoing a primary, elective operation of coronary artery bypass grafting (CABG) with ECC. Biological tests were performed at 4 different time points during the operation.A marked reduction in the placebo group of ristocetin-induced platelet agglutination (binding of von Willebrand factor [vWF] to platelet glycoprotein [GP] Ib) was shown during ECC and at the end of surgery, but not in the aprotinin group. This abnormality is not related to the hydrolysis of vWF or GP Ib, since washed platelets were resuspended in pooled normal plasma which provided a constant amount of vWF in this test and since the plasma concentration of the fragment of GP Ib (glycocalicin) did not correlate with this abnormality.Despite a high concentration of heparin (5-7 IU/ml) in patient's plasma during bypass, activation of blood coagulation in both groups was evidenced by an increase in ATm (thrombin-modified antithrombin III) level. The level of ATm in the placebo group reached a maximum at the end of ECC during rewarming, while in the aprotinin group, ATm level at this time point was significantly lower than in the control group. In comparison to the placebo group, the generation of the fibrin degradation products (DDE complexes) was inhibited by aprotinin during ECC, but the level of DDE complexes in the aprotinin group was slightly elevated after ECC, although much less than in the placebo group. Other parameters measured did not show significant differences between the two groups.These results indicate that the hemostatic defect in patients during and after ECC may result, at least in part, from the impairment of GP Ib-dependent platelet adhesion. Therefore, the administration of aprotinin in ECC may improve hemostasis by abrogating this impairment, in addition to the protective effect of aprotinin on hemostatic plug. Activation of blood coagulation occurs during cardiopulmonary bypass despite heparin therapy and this activation seems to be partially inhibited by aprotinin administration.
Treatment of Uremic Anemia with Recombinant Erythropoietin also Reduces the Defects in Platelet Adhesion and Aggregation Caused by Uremic Plasma
Authors: Zwaginga Jaap J , IJsseldijk Martin J W , de Groot Philip G , Kooistra Menno , Vos Jaap , van Es A , Koomans Hein A , Struyvenberg A , Sixma Jan J 
Published: July 2018

SummaryIn the present study, uremic patients on chronic maintenance hemodialysis were treated with recombinant erythropoietin. Before and after 20 weeks of treatment, platelet adhesion and aggregation were studied with perfusions over a sprayed collagen surface and over matrix of cultured endothelial cells with high tissue factor activity. The influence of the erythropoietin induced raise in hematocrit on platelet transport and adhesion was excluded by performing the perfusions at a standard red blood cell concentration. The present study clearly demonstrates that erythropoietin treatment improves platelet adhesion and aggregation in addition to and independent of its effect on the hematocrit.Studies with control platelets resuspended in plasma of untreated patients showed that a uremic plasma factor reduced adhesion and thrombin- and collagen-dependent aggregation. Patient platelets resuspended in control plasma showed no defects. After erythropoietin treatment, the plasma-induced inhibition of adhesion and aggregation had almost completely disappeared from patient plasma.The beneficial effect of the erythropoietin treatment on uremic hemostasis is therefore twofold. The increase of the red blood cell mass improves transport of platelets, and thus adhesion to the vessel wall. The intrinsic defect due to the presence of an inhibitory toxin in uremic plasma is, in large part, corrected. Improved neutralization of uremic toxins by red blood cells or less production of toxins by better oxygenated tissue might play a role in the observed phenomena.
Effects on Coagulation and Fibrinolysis of Desmopressin in Patients Undergoing Total Hip Replacement
Authors: Flordal Per Anders , Ljungström Karl-Gösta , Svensson Jan , Ekman Brenda , Neander Gustaf 
Published: July 2018

SummaryTwelve patients undergoing total hip replacement, with regional anaesthesia and with dextran infusion for plasma expansion and thromboprophylaxis, were given the vasopressin analogue desmopressin (DDAVP) or placebo in a randomized, double-blind prospective study. In controls (n = 6) we found a prolongation of the bleeding time, low factor VIII (FVIII) and von Willebrand factor (vWF) and a decrease in antithrombin III to levels known to be at risk for venous thrombosis. Desmopressin shortened postoperative bleeding time, gave an early FVIII/vWF complex increase, prevented antithrombin III from falling to critically low values and appeared to activate the fibrinolytic system, both by tPA increase and PAI-1 decrease.Thus in the controls we found changes in both coagulation and fibrinolysis indicating a haemorrhagic diathesis as well as a risk for thromboembolism. Desmopressin induced factor changes that possibly reduce both risks.
Inhibitory Effect of Retinoids on the Generation of Procoagulant Activity by Blood Mononuclear Phagocytes
Authors: Conese M , Montemurro P , Fumarulo R , Giordano D , Riccardi S , Colucci M , Semeraro N 
Published: July 2018

SummaryRetinoids are known to modulate several functions of mononuclear phagocytes. We have studied the effect of retinyl acetate (RAc) and retinoic acid (RA) on the production of procoagulant activity (PCA) by human peripheral blood mononuclear cells stimulated with endotoxin (1 εg/ml, 4 or 20 h at 37°C). Both compounds caused a dose-dependent reduction in the expression of cell-associated PCA (from 86 to <10% of control in the range of concentration comprised between 0.1 and 100 εM). This effect was also observed when the cells were exposed to retinoids for 10 min and washed before challenge with endotoxin, indicating that it is rapid and irreversible. In contrast, incubation of RAc or RA for 3 h at 37° C with cells that have been already stimulated with endotoxin (20 h at 37° C) remained without influence on cell PCA. The inhibitory action of retinoids was also observed when monocyte-enriched (>85%) preparations or highly purified monocyte-derived macrophages (>99%) were used instead of whole mononuclear cells. BW755C, an inhibitor of cyclo-oxygenase and lipoxygenase, reversed the inhibitory effect of retinoids, whereas acetylsalycilic acid, an inhibitor of cyclo-oxygenase, was inactive, suggesting the involvement of a lipoxygenase product. The inhibition of monocyte/macrophage PCA production and the subsequent reduction of cell potential for fibrin deposition might represent one of the mechanisms whereby retinoids exert their antiinflammatory and immunomodulatory activities.
In Vitro Studies of Antiphospholipid Antibodies and Its Cofactor, β2-Glycoprotein I, Show Negligible Effects on Endothelial Cell Mediated Protein C Activation
Authors: Oosting Janine D , Derksen Ronald H W M , Hackeng Tilman M , van Vliet Marja , Preissner Klaus T , Bouma Bonno N , de Groot Philip G 
Published: July 2018

SummaryThe effect of sera and purified IgG isolated from plasma of 46 patients with systemic lupus erythematosus (SLE) and 9 healthy donors on the endothelial cell (EC) mediated protein C activation was investigated. Out of the 46 SLE sera used, 19 were antiphospholipid antibodies (aPL) positive. From 12 patients IgG was isolated, of which 6 contained aPL. EC were first incubated with IgG (7 mg/ml) or serum (1: 1 diluted) for 1 h and then tested for their ability to promote protein C activation by thrombin, with the cells either in a monolayer or in a suspension. The normal range (mean of control values ± 2 SD) of protein C activation was 80-120%. In contrast to others, we could not detect an inhibition of protein C activation by any of the patient IgG's or sera.The recently described cofactor for binding of antiphospholipid antibodies to phospholipids, β2-glycoprotein I, was purified and added to the purified IgG's. A combination of these two components did not inhibit the EC mediated protein C activation by thrombin.This study suggests that the inhibition of the protein C activation, mediated by EC, is not a general mechanism by which aPL related thrombosis can be explained.
Influence of Intrinsic and Extrinsic Plasminogen upon the Lysis of Thrombi In Vitro
Authors: Nishino N , Kakkar V V , Scully M F 
Published: July 2018

SummaryWhen the rate of lysis of artificial thrombi (prepared from plasma or whole blood) was expressed according to the concentration of tissue type plasminogen activator (t-PA) or single chain urokinase type plasminogen activator (sc-uPA) then bell-shaped dose response curves were obtained, low rates being observed at concentrations of activator greater than 500 units/ml. Bell-shaped dose response curves were not observed for rate of lysis of artificial thrombi over the concentrations of streptokinase tested (SK) or for the lysis of plasma gel clots by any of the activators tested. Further investigation indicated that the preponderant mechanism for dissolution of thrombi at 500 units/ml of t-PA was by activation of the plasminogen within the thrombus (intrinsic) since the plasminogen present in the plasma perfusing the thrombus (extrinsic) rapidly became depleted. On the other hand, at 50 units/ml t-PA the lysis was observed to be due preponderantly to the action of plasmin arising from extrinsic rather than intrinsic plasminogen. If "plasminogen enriched" thrombi were prepared in the presence of Lys plasminogen (Lys-Plg) faster rates of lysis occurred and bell-shaped biometric curves were not observed.