bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of over-the-scope-clip (OTSC) improves outcomes of high-risk adverse outcome (HR-AO) non-variceal upper gastrointestinal bleeding (NVUGIB)
Authors: Asokkumar Ravishankar , Soetikno Roy , Sanchez-Yague Andres , Kim Wei Lim , Salazar Ennaliza , Ngu Jing 
Published: July 2018

Abstract
Background and study aims Endoscopic treatment of non-variceal upper gastrointestinal bleeding (NVUGIB) with high-risk adverse outcome (HR-AO) features has a high risk of failure. We studied the safety and efficacy of over-the-scope clips (OTSC) to treat these lesions.
Patients and methods We included patients who were treated using OTSC for NVUGIB from January 2015 to October 2017. We studied rebleeding and mortality rates and used the Rockall data and our institution’s prior data for comparison. We used descriptive and chi-square statistics.
Results We studied 18 patients with 19 bleeding lesions: 9 (47 %) duodenal ulcers, 4 (21 %) Dieulafoy’s lesion, 3 (16 %) gastric ulcer, and 3 (16 %) bleeding after gastric biopsy, gastric polypectomy and endoscopic ultrasound-guided fine-needle aspiration of peri-gastric mass. We applied OTSC as the first-line treatment in 10 (53 %) and as the second-line treatment in 9 (47 %) bleeding lesions. Continued bleeding after OTSC occurred in six patients, but we treated it successfully and achieved complete hemostasis in all patients. We found OTSC use significantly decreased (0 % vs. 53 %, P < 0.01) and reduced (0 % vs. 24 %, P = 0.08) the rebleeding rate in our high-risk (RS ≥ 8) and intermediate-risk (RS = 4 – 7) Rockall score patients as compared to the rates reported by the Rockall study, respectively. When compared to our institution’s prior study, we found a decrease in the rebleeding rate with OTSC (0 % vs. 21 %, P = 0.06) in our intermediate-to-high risk Rockall score patients (RS ≥ 4). There was no difference in mortality rates as compared to both control studies.
Conclusion Use of OTSC is safe, efficacious and appears superior to standard treatment for HR-AO NVUGIB. OTSC should be considered as first-line treatment for HR-AO bleeding.
„Medikamentös ausbehandelte Fluktuationen“ trotz „optimierter peroraler/transdermaler Therapie“ bei Morbus Parkinson: Versuch einer pragmatischen Definition
Authors: Ebersbach Georg , Poewe Werner 
Published: July 2018

ZusammenfassungIm Verlauf der Behandlung des idiopathischen Parkinson-Syndroms (IPS) kann es dazu kommen, dass L-Dopa-induzierte motorische Komplikationen (Wirkfluktuationen und Dyskinesien) nicht mehr suffizient durch Anpassung der oralen oder transdermalen Medikation beherrschbar sind. Diese Situation wird unter anderem mit dem Begriff „medikamentös ausbehandelte Fluktuationen“ (MAF) umschrieben und bildet den Ausgangspunkt für eskalierende Therapieentscheidungen mit teilweise weitreichender Bedeutung für die Alltagsabläufe, Lebensqualität und Zukunftsperspektiven der betroffenen Patienten und für ihr Umfeld. Nationale und internationale Leitlinien empfehlen, zu diesem Zeitpunkt die (Differenzial-)Indikation für eine der derzeit etablierten eskalierten Therapien mittels tiefer Hirnstimulation (THS), kontinuierlicher subkutaner Apomorphin-Infusion (APO) oder intrajejunaler Infusion von Levodopa-Gel (IJLG) zu prüfen. Obwohl die Termini „medikamentös ausbehandelte“ bzw. „refraktäre“ Fluktuationen/Dyskinesien intuitiv genauso verständlich erscheinen wie der eng damit verbundene Begriff der „optimierten Medikation“, handelt es sich letztlich um Konstrukte, die in Leitlinien nicht konkret definiert und daher einer subjektiven individuellen Beurteilung anheimgestellt werden. Weil die Feststellung von „MAF“ weitreichende therapeutische Konsequenzen hat, wird in diesem Artikel ein pragmatischer Algorithmus für die Optimierung der Medikation bei Fluktuationen und Dyskinesien vorgestellt, der zur Operationalisierung des Begriffs der MAF beitragen soll. Außerdem soll die Frage diskutiert werden, ob und unter welchen Umständen bei der Indikationsstellung zur THS oder anderen Eskalationstherapien auf eine vorangehende Optimierung der oralen/transdermalen Medikation verzichtet werden kann. Neben einer methodischen Analyse der vorhandenen therapeutischen Optionen bedeutet die individuelle Festlegung, ab welchem Zeitpunkt Komplikationen der oral-medikamentösen Therapie als nicht mehr tolerabel betrachtet werden, immer auch eine Berücksichtigung der Präferenzen und Bedenken des einzelnen Patienten. Eine pragmatische Definition von MAF ersetzt daher nicht eine individualisierte Entscheidungsfindung für eine eskalierte Therapie im Sinne eines „shared informed decision making“, sondern soll dem Behandler therapeutische Grundregeln für diesen Prozess an die Hand geben.
Des-Gamma-Carboxyprothrombin (PIVKA II) and Plasma Vitamin K1 in Newborns and Their Mothers
Authors: von Kries R , Shearer M J , Widdershoven J , Motohara K , Umbach G , Göbel U 
Published: July 2018

SummaryAssessments of the vitamin K status in newborns and their mothers by means of des-γ-carboxy-prothrombin (PIVKA II) measurement have given equivocal results. Part of the variability could be attributed to differences in sensitivity (i.e. the ability to detect small concentrations) and validity (i.e. ability to detect vitamin K deficiency) of the methods applied. None of these methods have yet been validated with respect to plasma vitamin K1. In 22 healthy mother/infant pairs PIVKA II was determined using three different assays including ratio Xa/ecarin (Xa/ec), crossed immunoelectrophoresis (CIE), and an ELISA with a monoclonal antibody (MAB). The results were compared with conventional clotting tests and plasma vitamin K1. The following results were obtained:Cord blood: Clotting tests within age-related normal ranges; PIVKA II detection rates: 0/22 (Xa/ec), 1/22 (CIE), 4/22 (MAB); plasma vitamin K1: undetectable in 20/22.Mothers: Clotting tests all within normal range; PIVKA II detection rates: 1/22 (Xa/ec), 0/22 (CIE), 5/22 (MAB); plasma vitamin K1 (pg/ml) for all mothers (median; range): 186; 55–833; for PIVKA II positive mothers: 213; 59–699.PIVKA II detectability in newborns and mothers was not correlated. The results show an increase in sensitivity for PIVKA II detection in the order of MAB ≫CIE >Xa/ec. Due to the very low plasma vitamin K1 at birth, no correlation was possible between cord PIVKA II detectability and plasma vitamin K1. However, in mothers at term PIVKA II MAB appears to be unrelated to the vitamin K status.
Serum Osteocalcin as a Marker for Vitamin K-Status in Pregnant Women and Their Newborn Babies
Authors: Jie Kon-Siong G , Hamulyák Karly , Gijsbers Birgit L M G , Roumen Frans J M E , Vermeer Cees 
Published: July 2018

SummaryOsteocalcin (bone Gla-protein) is a vitamin K-dependent protein synthesized by osteoblasts. Its hydroxylapatite binding capacity (HBC) is generally used to estimate the Gla-content of circulating osteocalcin. Here we have used the HBC of serum osteocalcin as a marker for the vitamin K-status in pregnant women and their offspring. For all cases investigated the HBC values in the cord samples were substantially lower than in the corresponding maternal ones. Babies from mothers who had been treated with vitamin K during the last 6 weeks prior to delivery, had significantly higher HBC values than those from a placebo group. The results presented in this paper are indicative for a generally occurring vitamin K deficiency in newborns. At delivery the HBC in untreated women was low as well. In both the placebo- and the vitamin K-group a good correlation was found between the HBC values in paired samples from mother and child. Whether the maternal HBC value may be used as a prenatal marker for estimating the fetal vitamin K-status remains to be seen.
Multicentric Evaluation of a New Assay for Prothrombin Fragment F1+2 Determination
Authors: Bruhn H D , Conard J , Mannucci M , Monteagudo J , Pelzer H , Reverter J C , Samama M , Tripodi A , Wagner C 
Published: July 2018

SummaryA multicenter study of a recently developed ELISA for the determination of prothrombin fragment Fl+2 was performed in order to evaluate analytical and clinical aspects.Mean intra-assay and inter-assay reproducibility were found to be 11.0 and 12.6%, respectively. The measuring range covered by the calibration curve reaches from 0.04 to 10.0 nM/1 Fl+2. Testing 133 healthy subjects a reference range of 0.37 to 1.11 nM/1 Fl+2 (2.5–97.5 percentile) with a median of 0.66 nM/1 F1+2 was calculated. Minor difficulties with blood sampling (venous occlusion for 2 min) did not affect Fl+2 plasma concentrations.Significantly increased F1+2 levels were measured in patients with leukemia (p <0.0001), severe liver disease (p <0.005) and after myocardial infarction (p <0.01). Elevated F1+2 concentration before the beginning of heparin therapy (1.25 nM/1) decreased to 0.77 nM/1 (p <0.0001) after 1 day of therapy. For patients in the stable phase of oral anticoagulant therapy decreasing Fl+2 concentrations were measured with increasing INR. Fl+2 levels were already significantly reduced in patients with INR <2.0 (0.56 nM/1; p = 0.0005). Thus Fl+2 determination may be helpful in identifying activation processes as well as in monitoring anticoagulant therapy.
Collaborative Study of a Proposed International Standard for Plasma Fibrinogen Measurement
Authors: Gaffney Patrick J , Wong M Y 
Published: July 2018

SummaryThere is increased interest in the relationship between plasma fibrinogen levels and the incidence of coronary artery disease. The National Institute for Biological Standards and Control (UK) has completed a study to establish an International Standard for plasma fibrinogen. This study was conducted using a recommended assay procedure to measure the clottable material present in the proposed lyophilised Standard (coded 89/644). Twenty-two laboratories from nine countries took part in the study and analysis of the data allowed the calibration of 89/644 at 2.4 mg/ml clottable protein. Agreement with this figure was established in two laboratories using three or more different assays for plasma fibrinogen. Degradation studies of the proposed plasma fibrinogen Standard suggested that no loss of clottable protein was observed when the lyophilised material was stored at 20° C for 1 year.The Fibrinogen Sub-Committee of the ISTH (Amsterdam, The Netherlands, June 1991) supported the establishment of 89/644 as an International Standard. This collaborative study will be presented to the Expert Committee on Biological Standardisation of the World Health Organisation at their 1992 session. In the meantime 89/644 will be distributed as the proposed International Standard for plasma fibrinogen measurement containing 2.4 mg/ ml clottable protein.
Mutations in Severe, Type III von Willebrand’s Disease in the Dutch Population: Candidate Missense and Nonsense Mutations Associated with Reduced Levels of von Willebrand Factor Messenger RNA
Authors: Eikenboom Jeroen C J , Ploos van Amstel Hans K , Reitsma Pieter H , Briët Ernest 
Published: July 2018

SummaryThe von Willebrand factor (vWF) genes of nine unrelated, severe, type III von Willebrand’s disease (vWD) patients (six of Dutch origin) and four unrelated Dutch type I vWD patients were screened for mutations in exons that contain CGA codons (Arg), which are liable to mutation to TGA stop codons. The nine exons of the vWF gene (3, 8, 9, 10, 28, 31, 32, 43 and 45) that contain all the CGA codons (11 in total) of the vWF cDNA were amplified by the polymerase chain reaction and screened for mutations by single-strand conformation polymorphism analysis, restriction enzyme – and/or nucleotide sequence analysis. Three of the severe vWD patients were found to be heterozygous for a nonsense mutation: CGA Arg 2535 → TGA Stop. Three other severe vWD patients were homozygous for a single nucleotide substitution, AAC Asn 2546 → TAC Tyr. The transcription of these mutated alleles was tested by cDNA dependent amplification of platelet RNA. The level of transcription product was strongly reduced for either mutant allele.
A Specific Immunologic Assay for Functional Plasminogen Activator Inhibitor 1 in Plasma – Standardized Measurements of the Inhibitor and Related Parameters in Patients with Venous Thromboembolic Disease
Authors: Philips Malou , Juul Anne-Grethe , Selmer Johan , Lind Bent , Thorsen Sixtus 
Published: July 2018

SummaryA new assay for functional plasminogen activator inhibitor 1 (PAI-1) in plasma was developed. The assay is based on the quantitative conversion of PAI-1 to urokinase-type plasminogen activator (u-PA)-PAI-l complex the concentration of which is then determined by an ELISA employing monoclonal anti-PAI-1 as catching antibody and monoclonal anti-u-PA as detecting antibody. The assay exhibits high sensitivity, specificity, accuracy, and precision. The level of functional PAI-1, tissue-type plasminogen activator (t-PA) activity and t-PA-PAI-1 complex was measured in normal subjects and in patients with venous thromboembolism in a silent phase. Blood collection procedures and calibration of the respective assays were rigorously standardized. It was found that the patients had a decreased fibrinolytic capacity. This could be ascribed to high plasma levels of PAI-1. The release of t-PA during venous occlusion of an arm for 10 min expressed as the increase in t-PA + t-PA-PAI-1 complex exhibited great variation and no significant difference could be demonstrated between the patients with a thrombotic tendency and the normal subjects.
Comparative Arterial Antithrombotic Activity of Clopidogrel and Acetyl Salicylic Acid in the Pig
Authors: Samama Ch M , Bonnin Ph , Bonneau M , Pignaud G , Mazoyer E , Bailliart O , Maffrand J P , Viars P , Caen J P , Drouet L O 
Published: July 2018

SummaryWe investigated the comparative antithrombotic properties of clopidogrel, an analogue of ticlopidine, and aspirin, using the Folts' model on femoral arteries in 22 pigs. On each animal, clopidogrel or aspirin were used to treat the thrombotic process on the left femoral artery and to prevent this process on the right femoral artery. Sequentially: an injury and stenosis were carried out on the left femoral artery; the thrombotic process was monitored with a Doppler during a 30-min observation period for cyclic flow reductions or permanent cessation of flow; after the first cyclic flow reduction occurred, clopidogrel (5 mg kg-1) or aspirin (2.5, 5, 100 mg kg-1) were injected intravenously; if cyclic flow reductions were abolished, epinephrine (0.4 µg kg-1 min-1) was injected to try to restore cyclic flow reductions and/or permanent cessation of flow; then injury and stenosis were applied on the right femoral artery. Before and after injection of clopidogrel or aspirin, ear immersion bleeding times and ex-vivo platelet aggregation were performed. Clopidogrel (n = 7) abolished cyclic flow reductions in all animals and epinephrine did not restore any cyclic flow reduction. On the right femoral artery, cyclic flow reductions were efficiently prevented, even for two injuries. Basal bleeding time (5 min 28) was lengthened (>15 min, 30 min after clopidogrel and remained prolonged even after 24 h). ADP-induced platelet aggregation was inhibited (more than 78%). Comparatively, aspirin had a moderate and no dose-dependent effect. Aspirin 2.5 mg kg-1 (n = 6) abolished cyclic flow reductions in 2 animals, CFR reoccurred spontaneously in one animal and epinephrine restored it in a second animal. Aspirin 5 mg kg-1 (n = 6) abolished cyclic flow reductions in only 3 animals and epinephrine always restored it. Aspirin 100 mg kg-1 (n = 3) was unable to abolish cyclic flow reductions. On the right femoral artery, aspirin did not significantly prevent cyclic flow reductions which occurred in all animals after one (n = 14) or two injuries (n = 1), except for one animal. Basal bleeding time was lengthened but it shortened rapidly, reaching its basal value after 24 h. ADP-induced aggregation was not significantly inhibited, whereas arachidonic acid induced aggregation was always inhibited. Clopidogrel appears as a more potent antithrombotic drug than aspirin in this model, in treating and preventing spontaneous or epinephrine-induced cyclic flow reductions and lengthening bleeding time.
Structure, Kinetics, and Function of Human and Rhesus Plasma Prekallikreins Are Similar
Authors: Veloso Dulce , Smith Joseph I , Denny Stephen , Cosgriff Thomas M 
Published: July 2018

SummaryTo determine if rhesus monkeys (Macaca mulatta) could serve as a model for studying the role of the contact system in the pathophysiology of human infections, we compared structural, kinetic, and functional characteristics of plasma prekallikrein and its activation products in rhesus and humans. Three prekallikrein variants (85-, 89- and 93-kDa) were revealed in rhesus plasma as compared with the two variants (85- and 88-kDa) in human plasma by immunoblotting with the monoclonal antibody MAb 13G11. The prekallikrein concentration in rhesus plasma was 1.5-fold that in human plasma as determined by computerized immunoblot analyses (CIBA) and amidolytic activity. The electrophoretic mobility of prekallikrein from plasma of both species increased after deglycosylation. Inhibition of prekallikrein activation by MAb 13G11 was 55% (rhesus plasma) and 76% (human plasma), with similar inhibition curves. Immunoblots of activated rhesus plasma showed prekallikrein, complexes of kallikrein with C1 inhibitor, α2-macroglobulin and ~60-kDa inhibitor(s) (viz. antithrombin III), and 45-kDa fragments, like those in activated human plasma. Concentrations and molecular masses of factor XII and high molecular weight kininogen were similar in rhesus and human plasma. The activated partial thromboplastin time (APTT) and prothrombin time were 20.1 ± 1.6 and 9.7 ± 0.3 s for rhesus and 32.0 ±5.6 and 12 ± 0.5 s for human plasma. Human and rhesus APTTs were similar when prekallikrein concentrations in human and rhesus plasma became alike by adding human purified prekallikrein. We conclude that the contact systems of rhesus and humans are similar in many respects and that rhesus should be a useful model to study the role of the contact system in the pathophysiology of human infectious diseases.
The Influence of Glycosylation on the Catalytic and Fibrinolytic Properties of Pro-Urokinase
Authors: Lenich Catherine , Pannell Ralph , Henkin Jack , Gurewich Victor 
Published: July 2018

SummaryWe previously found that human pro-UK expressed in Escherichia coli is more active in fibrinolysis than recombinant human pro-UK obtained from mammalian cell culture media. To determine whether this difference is related to the lack of glycosylation of the E. coli product, we compared the activity of E. coli-derived pro-UK [(-)pro-UK] with that of a glycosylated pro-UK [(+)pro-UK] and of a mutant of pro-UK missing the glycosylation site at Asn-302 [(-) (302) pro-UK]. The latter two pro-UKs were obtained by expression of the human gene in a mammalian cell. The nonglycosylated pro-UKs were activated by plasmin more efficiently (≈2-fold) and were more active in clot lysis (1.5-fold) than the (+)pro-UK. Similarly, the nonglycosylated two-chain derivatives (UKs) were more active against plasminogen and were more rapidly inactivated by plasma inhibitors than the (+)UK.These findings indicate that glycosylation at Asn-302 influences the activity of pro-UK/UK and could be the major factor responsible for the enhanced activity of E. coli-derived pro-UK.
Adrenergic Stimulation of Regional Plasminogen Activator Release in Rabbits
Authors: Chandler W L , Loo S C , Mornin D 
Published: July 2018

SummaryThe purpose of this study was to determine whether different regions of the rabbit vascular system show variations in the rate of plasminogen activator (PA) secretion. To start, we evaluated the time course, dose response and adrenergic specificity of PA release. Infusion of 1 µg/kg of epinephrine stimulated a 116 ± 60% (SD) increase in PA activity that peaked 30 to 60 s after epinephrine administration. Infusion of 1 µg/kg of norepinephrine, isoproterenol and phenylephrine had no effect on PA activity. Pretreatment with phentolamine, an alpha adrenergic antagonist, blocked the release of PA by epinephrine while pretreatment with the beta blocker propranolol had no effect. This suggests that PA release in the rabbit was mediated by some form of alpha receptor.Significant arterio-venous differences in basal PA activity were found across the pulmonary and splanchnic vascular beds but not the lower extremity/pelvic bed. After stimulation with epinephrine, PA activity increased 46% across the splanchnic bed while no change was seen across the lower extremity/pelvic bed. We conclude that several vascular beds contribute to circulating PA activity in the rabbit, and that these beds secrete PA at different rates under both basal and stimulated conditions.
Human Platelets Exposed to Mechanical Stresses Express a Potent Lipoxygenase Product
Authors: Margalit Alon , Livne Avinoam A 
Published: July 2018

SummaryHuman platelets exposed to hypotonicity undergo regulatory volume decrease (RVD), controlled by a potent, yet labile, lipoxygenase product (LP). LP is synthesized and excreted during RVD affecting selectively K+ permeability. LP is assayed by its capacity to reconstitute RVD when lipoxygenase is blocked. Centrifugation for preparing washed platelets (1,550 × g, 10 min) is sufficient to express LP activity, with declining potency in repeated centrifugations, indicating that it is not readily replenish-able. When platelet suspension flows in a vinyl tubing (1 mm i.d.), at physiological velocity, controlled at 90–254 cm/s, LP formation increases as a function of velocity but declines as result of increasing the tubing length. Stirring the platelets in an aggregometer cuvette for 30 s, yields no LP unless the stirring is intermittent. No associated platelet lysis or aggregation are observed following the mechanical stress applications. These results demonstrate that although mechanical stresses result in LP production, the mode of its application plays a major role. These results may indicate that LP is synthesized under pathological conditions and could be of relevance to platelets behavior related to arterial stenosis.
Effect of Platelet Encapsulated lloprost on Platelet Aggregation and Adhesion to Collagen and Injured Blood Vessels In Vitro
Authors: El-Gamal B A B , Pfliegler G , Crawford N 
Published: July 2018

SummaryA novel approach to site-directed delivery of drugs in vivo using blood platelets as carrier vehicles is being investigated. In this context some initial studies are reported on the effect of platelet encapsulated anti-platelet drugs on platelet aggregation and adhesion to fibrillar collagen and injured arteries in vitro. The stable prostacyclin analogue lloprost has been encapsulated within human and pig platelets by high voltage electroporation (Hughes and Crawford 1989 and 1990). After resealing the platelets, the packaged drug has a negligible effect upon platelet adhesion to a surface of fibrillar collagen or to damaged aorta (stripped to the tunica media to simulate deep injury). The rate of platelet recruitment to the collagen shows no dose dependency with respect to intracellular lloprost concentrations. After high lloprost loading, as few as 2% drug loaded platelets in a mixture with control (sham encapsulated) platelets, inhibit agonist-induced platelet aggregation >50%. The prior deposition of a “lawn” of Iloprost-loaded platelets onto fibrillar collagen or damaged aorta has a substantial inhibitory effect (50–70%) upon the secondary recruitment of normal platelets compared with recruitment to a “lawn” of normal platelets. This inhibition of secondary recruitment occurs even in the presence of a platelet activator. If reduction of platelet recruitment to a vessel wall lesion results in a decrease in the local concentration of platelet granule-derived smooth muscle cell chemotactic and proliferative factors, this site-directed drug delivery may well have application for the prevention of restenosis following balloon angioplasty procedures.