bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of Ultrasound in the Diagnostic Work-Up of Adult Intussusception – A Multicenter Retrospective Analysis
Authors: Klinger Christoph , Riecken Bettina , Dietrich Christoph Frank , Dirks Klaus , Caca Karel , Fröhlich Eckhart 
Published: July 2018

Abstract
Purpose To evaluate the use of ultrasound (US) in the diagnostic work-up of adult intussusception (AI).
Methods This multicenter study includes 26 consecutive patients diagnosed with AI between January 2010 and November 2017. A retrospective chart analysis was conducted with a focus on abdominal US findings and diagnostic accuracy of different imaging modalities (ultrasound, computed tomography (CT), magnetic resonance imaging). If available, surgical and pathological findings served as the gold standard (76.9 %). US examiners certified according to DEGUM grade 2 or 3 were classified as experts. Otherwise, they were regarded to have basic skills.
Results During diagnostic work-up, 92.3 % underwent abdominal US. US was the first-line imaging modality in 88.5 % of cases. The accuracy regarding the detection of AI (85 %), correct localization (95 %) and detection of complications (100 %) was excellent and comparable with CT (81 %, 90.5 %, and 91.7 %) when performed by experts. 72.7 % of tumorous lead points were detected by experienced examiners. In contrast, AI was detected in only 45.5 % of cases by examiners with basic skills. AI was diagnosed prior to surgery in all patients.
Conclusion US is reliable in the diagnostic work-up of AI when performed by experienced examiners with high-quality equipment. US, CT and MRI should be used in a complementary fashion since combination provides excellent sensitivity regarding the detection and correct localization of AI as well as the detection of complications. The impact of real-time imaging is illustrated by supplementary videos.
A Novel Study Design to Systematically Explore the Impact of Trial Methodology on Psychopharmacological Treatment Outcome in Patients with Depression
Authors: Severus Emanuel , Sauer Cathrin , Bauer Michael , Ostacher Michael , Anghelescu Ion-George 
Published: July 2018

Abstract
Introduction Randomized, double-blind, placebo-controlled trials were developed to draw rather unbiased conclusions regarding the efficacy of antidepressants in the treatment of a major depressive episode (internal validity), mostly with the purpose of formal approval of new compounds in this indication. However, at the same time, data suggest that the very process of randomization and blinded administrations of placebo will have a significant impact on the efficacy of the antidepressant tested and therefore may limit the external validity of results obtained from this type of studies. Therefore, there is an urgent need to systematically study the impact of randomization/placebo control/blinding on patient population, efficacy, tolerability, and external validity in the psychopharmacological treatment of patients with a major depressive episode.
Methods To develop a study design that allows the systematic exploration of the impact of trial design on characteristics of included patient population and outcome.
Results We propose a study design including sample size calculation and statistical analysis in which patients with a major depressive episode are randomized to 3 distinct study designs that differ with regard to control, randomization, and blindness.
Discussion The results of the proposed study design may have substantial consequences when it comes to how to best interpret the results of traditional randomized, double-blind, placebo-controlled trials in the acute treatment of major depressive disorder. Furthermore, they may lead to the implementation of new study designs that may be more suitable for assessing the effectiveness of new antidepressant compounds in everyday clinical practice.
A Comparative Analysis of D-Dimer Assays in Patients with Clinically Suspected Pulmonary Embolism
Authors: van Beek Edwin J R , van den Ende Bram , Berckmans René J , van der Heide Yvonne T , Brandjes Dees P M , Sturk Augueste , ten Cate Jan W 
Published: July 2018

SummaryTo avoid angiography in patients with clinically suspected pulmonary embolism and non-diagnostic lung scan results, the use of D-dimer has been advocated. We assessed plasma samples of 151 consecutive patients with clinically suspected pulmonary embolism. Lung scan results were: normal (43), high probability (48) and non-diagnostic (60; angiography performed in 43; 12 pulmonary emboli). Reproducibility, cut-off values, specificity, and percentage of patients in whom angiography could be avoided (with sensitivity 100%) were determined for two latex and four ELISA assays.The latex methods (cut-off 500 μg/1) agreed with corresponding ELISA tests in 83% (15% normal latex, abnormal ELISA) and 81% (7% normal latex, abnormal ELISA). ELISA methods showed considerable within- (2–17%) and between-assay Variation (12–26%). Cut-off values were 25 μg/l (Behring), 50 μg/l (Agen), 300 μg/l (Stago) and 550 μg/l (Organon). Specificity was 14–38%; in 4–15% of patients angiography could be avoided.We conclude that latex D-dimer assays appear not useful, whereas ELISA methods may be of limited value in the exclusion of pulmonary embolism.
Molecular Conversions of Recombinant Staphylokinase During Plasminogen Activation in Purified Systems and in Human Plasma
Authors: Ueshima S , Silence K , Collen D , Lijnen H R 
Published: July 2018

SummaryRecombinant staphylokinase (STAR) is produced as a 136 amino acid protein with NH2-terminal sequence Ser-Ser-Ser (mature STAR, HMW-STAR), which may be converted to lower molecular weight forms (LMW-STAR) by removal of the first six residues (yielding STAR-Δ6 with NH2-terminal Gly-Lys-Tyr-) or the first ten residues (yielding STAR-Δ10 with NH2-terminal Lys-Gly-Asp-). In the present study the occurrence and effects of these conversions during plasminogen activation by HMW-STAR were studied in purified systems and in human plasma.In stoichiometric mixtures of HMW-STAR and native human plasminogen (Glu-plasminogen), rapid and quantitative conversion of HMW-STAR to LMW-STAR occurred, concomitant with exposure of the active site in the plasmin-STAR complex. NH2-terminal amino acid sequence analysis revealed the sequence Lys-Gly-Asp- in addition to the known sequences of the Lys-plasmin chains, identifying STAR-Δ10 as the derivative generated from HMW-STAR. In mixtures of catalytic amount of HMW-STAR and human plasminogen, plasmin generation occurred progressively, following an initial lag phase, during which HMW-STAR was converted to LMW-STAR. Plasmin-mediated conversion of HMW-STAR to LMW-STAR obeyed Michaelis-Menten kinetics with K
m = 3.6 μM and k
2 = 0.38 s−1. The specific clot lysis activities of HMW-STAR (122,000 ± 8,000 units/mg) and LMW-STAR (129,000 ± 8,000 units/mg) were indistinguishable.In an in vitro system consisting of a 60 μl plasma clot submerged in 250 μl plasma, 80% clot lysis within 1 h was obtained with 70 nM HMW-STAR. This was associated with fibrinogen depletion and conversion of 20% of the HMW-STAR to LMW-STAR. Addition of 100 nM HMW-STAR to human plasma in the absence of a clot did not induce significant fibrinogen breakdown (≥ 90% residual fibrinogen after 2 h), and was not associated with significant coversion to LMW-STAR (≤10% within 2 h). With 400 nM HMW-STAR, fibrinogen depletion in plasma occurred within 1 h, and 80% conversion to LMW-STAR was observed. Thus, at fibrinolytically active concentrations which do not cause fibrinogen breakdown, no significant conversion of HMW-STAR to LMW-STAR occurs in human plasma in the absence of a clot.These findings indicate that the conversion of HMW-STAR to LMW-STAR may occur in association with clot lysis, but is not required to induce it.
Influence of Variability of Interpretation of Contrast Venography for Screening of Postoperative Deep Venous Thrombosis on the Results of a Thromboprophylactic Study
Authors: Couson Frédéric , Bounameaux Colette , Didier Cominique , Geiser Daniel , Meyerovitz Michael F , Schmitt Hans-Erich , Schneider Pierre-Alain , Bounameaux Henri 
Published: July 2018

SummaryTo assess interobserver variability of venography for screening for postoperative deep venous thrombosis (DVT), we used 185 bilateral ascending contrast venograms (366 lower limbs) which were performed using the long-leg film technique, in the frame of a trial of the efficacy of two low-molecular-weight-heparin fractions (initial evaluation). These venograms were submitted in a multicenter setting to three further readers who performed a serial scoring as DVT, no DVT or non-evaluable. DVTs were diagnosed in 78, 55 and 59/366 limbs (initial evaluation: 58). The proximal locations of DVTs were 16, 9 and 16 (initial evaluation: 15) and the non evaluable limbs 3, 5 and 18 (initial evaluation: 0). Apparent pairwise agreement between the three readers ranged from 87 to 90% (true coefficient of agreement Kappa 0.63-0.70). It ranged from 89 to 93% (Kappa 0.63-0.74) for the comparison between the readers and the initial evaluation. This considerable degree of disagreement among experienced readers should be taken into account in calculating sample sizes in prospective thromboprophylactic studies. Indeed, one of the two prophylactic regimens proved to be significantly (p = 0.012, p = 0.031, p = 0.049) or non-significantly (p = 0.073) superior to the other one depending upon the reading of venograms.
ARIC Hemostasis Study - III. Ouality Control
Authors: Chambless Lloyd E , McMahon Robert , Finch Andrea , Sorlie Paul , Heiss Gerardo , Lyles Robert , Wu Kenneth K 
Published: July 2018

SummaryMethods and results from the quality assurance program of the Atherosclerosis Risk in Communities (ARIC) Study regarding hemostasis variables are presented, following up previous reports in this journal on standardized procedures for blood collection and processing (7) and an organized plan for the performance of those procedures (8). Efforts were made to control for and assess all sources of variability, from venipuncture to laboratory analysis, including also local field center processing and sample shipping. The quality control program included (a) a standardized protocol for blood collection and processing; (b) training, certification, and annual recertification of field center personnel for blood collection and processing; (c) monitoring of fasting times, phlebotomy times, processing times, and shipping problems; (d) hemostatic laboratory internal quality control; (e) a replicate blood sample program; (f) an intraindividual variability study; and (g) continual monitoring of quality control and study participants’ data. This paper focused on items (c), (d), and (e). Measures of Variation, generally Standard deviations and coefficients of Variation, are estimated for replicate blood sampling and internal quality control data, for activated partial thromboplastin time, fibrinogen, factor VII and VIII activity, von Willebrand factor, antithrombin-III, and protein C. The results demonstrate that it is possible to reliably measure these hemostatic variables in a large multicenter study.
Antibodies to β2-Glycoprotein I Inhibit Phospholipid Dependent Coagulation Reactions
Authors: Brandt John T 
Published: July 2018

SummaryLupus anticoagulants are antibodies that inhibit phospholipid dependent coagulation reactions in vitro. These antibodies are of clinical interest because of their association with a variety of clinical manifestations characterized by microvascular thrombosis. Although these antibodies were originally thought to be directed at negatively charged phospholipid, recent studies have suggested that they may be directed at phospholipid-protein complexes. The effect of antibodies directed against β2-glycoprotein I (β2-GP I, apolipoprotein H) on phospholipid-dependent coagulation reactions has been studied. Polyclonal and monoclonal antibodies to β2-GP I were found to inhibit thrombin generation in a dose dependent manner. Inhibition of thrombin formation was due to specific interaction with β2-GP I. There was no evidence that inhibition was due to crossreactivity with other proteins involved in the prothrombinase complex. These findings document that antibodies directed against β2-GP I can have anticoagulant activity analogous to lupus anticoagulant activity and are consistent with the recent observation of such activity in lupus anticoagulant patient samples.
A Quantitative Thrombin Time for Determining Levels of Hirudin and Hirulog™
Authors: Reid Thomas J , Alving Barbara M 
Published: July 2018

SummaryThe anticoagulant effect of recombinant hirudin (rHir) and HirulogTM has been monitored in patients with the activated partial thromboplastin time. Accurate monitoring with this test cannot be achieved if plasmas contain heparin, lupus anticoagulants, low concentrations of fibrinogen or other factors, or elevated fibrinogen-fibrin degradation products (FDP). We have therefore developed a simple, rapid, sensitive clot-based method, the quantitative thrombin time (QTT), to measure levels of rHir and HirulogTM in patient plasma (or whole blood). The QTT is performed by mixing a 1:10 dilution of patient plasma (50 μl) with human fibrinogen (50 μl, 128 mg/dl) at 37° C; the clotting time is initiated by adding human thrombin (50 μl, 5-7.5 U/ml). The concentration of HirulogTM or rHir in plasma can be determined by comparing the QTT in patient plasma with a Standard curve that is generated by adding different concentrations of anticoagulant to pooled normal plasma. Studies with whole blood using the same procedure yield similar results. In the absence of HirulogTM or rHir, the baseline QTT is the same in normal and abnormal plasmas (fibrinogen <150 mg/dl and FDP as high as 1024 μg/ml, elevated FDP alone, lupus anticoagulant, or heparin <0.9 U/ml). When known concentrations of either rHir or HirulogTM are added to abnormal plasmas, the mean observed concentrations as determined by the QTT deviate from the expected values by less than 10% (range 0-19%). The data indicate that the QTT is a simple, rapid, and accurate test for the determination of levels of rHir and HirulogTM in plasma or whole blood.
Continuous Registration of Thrombin Generation in Plasma, Its Use for the Determination of the Thrombin Potential
Authors: Hemker H C , Wielders S , Kessels H , Béguin S 
Published: July 2018

SummaryA method is described by which the time-course of thrombin generation in plasma can be obtained from a continuous optical density recording of p-nitroaniline (pNA) production in a 2:3 diluted plasma. A chromogenic substrate, methylmalonyl-methylanalyl-arginyl-pNA (SQ68), is used that is specifically split by thrombin but at a low rate. The thrombin that appears and disappears in the plasma does not split more than 5% of the substrate added, so the rate of substrate conversion is in good approximation proportional to the amidolytic activity in the plasma over the entire period of thrombin generation. The course of the enzyme concentration can be calculated from the amidolytic activity curve. It is shown that the thrombin generation curves obtained in this way are essentially identical to those obtained via the classical subsampling method.The presence of SQ 68 influences the amount of free thrombin that appears in plasma because it competitively inhibits the inactivation of thrombin by AT III and α2 macroglobulin. The inhibition of the thrombin peak by heparin, relative to an uninhibited control, remains unaltered by the presence of the substrate.From the course of thrombin activity and the prevailing decay constants, the course of prothrombin conversion velocity can be calculated. Prothrombin conversion was seen to be inhibited at high (>500 μM) substrate concentrations only, and experimental conditions are found under which the inhibition of the clotting process by the substrate is negligibleThe amidolytic activity is the sum of the activities of free thrombin and of the α2 macroglobulin-thrombin complex formed. Via a mathematical procedure the amount of SQ 68 that has been split by thrombin alone and not by the a2 macroglobulin-thrombin complex, can be derived from the course of the optical density.The total amount of SQ 68 eventually split by thrombin alone is proportional to the surface under the thrombin generation curve, i. e. to the time-integral of free thrombin. This value, that we call the thrombin potential (TP), directly indicates how much of any physiological substrate can potentially be split by the thrombin being generated in the plasma.
Correlation Between Platelet Aggregation and Dephosphorylation of a 68 kDa Protein Revealed through the Use of Putative PKC Inhibitors
Authors: Turini Marco E , Gaudette Douglas C , Holub Bruce J , Kirkland James B 
Published: July 2018

SummaryThe efficacy of two structurally and functionally unrelated protein kinase C (PKC) inhibitors, chelerythrine and calphostin C, was assessed in intact human platelets by studying platelet aggregation in response to Stimulation with phorbol 12-myristate 13-acetate (PMA) or the thromboxane-A2 mimetic, U46619. Surprisingly, both inhibitors increased aggregation in response to PMA, but decreased aggregation in response to U46619. To further explore this phenomenon, gel electrophoresis of 32P-labelled proteins from PMA- or U46619-stimulated platelets in the presence and absence of the two putative PKC inhibitors was performed. Although neither chelerythrine nor calphostin C proved to be effective PKC inhibitors in intact human platelets, a strong correlation between the dephosphorylation of a 68 kDa protein and the rate of platelet aggregation was observed. From these results, the indiscriminate use of PKC inhibitors in whole platelets is questioned and attention is drawn to the role of protein dephosphorylation in platelet activation. The 68 kDa protein was the major phosphorylated substrate in resting platelets. Okadaic acid increased phosphorylation of this band, indicating active phosphate group turnover under resting conditions.
The Difference Between Platelet and Plasma FXIII Used to Study the Mechanism of Platelet Microvesicle Formation
Authors: Holme Pål André , Brosstad Frank , Solum Nils Olav 
Published: July 2018

SummaryThe formation of microvesicles from platelets was induced either by activation of the complement system by a monoclonal antibody to CD9, or by incubation of platelets with the calcium ionophore A23187. A filter technique to isolate the microvesicles without plasma contamination is described. The microvesicles contained FXIIIa2 from the platelet cytoplasm which shows that these particles contain significant amounts of intracellular material. This was shown by the use of crossed immunoelectrophoresis with rabbit antibodies to total human platelet proteins in the second dimension gel and polyclonal antibodies against the a- and b-subunit of FXIII in the intermediate gel. The FXIIIa2 in the microvesicle was found to be functional as an enzyme. To prove this, it was shown that FXIII in its immunoprecipitate arc could catalyze the incorporation of monodansylcadaverine into casein as identified by fluorescence of this arc in ultraviolet light. The observation that the plasma form of FXIII (FXIIIa2b2) was absent from the microvesicles collected by the filtration technique, whereas it was present in platelet fragments obtained by mechanical disruption by ultrasonication, indicates that the activation-dependent microvesicles are formed by a true budding process with the inclusion of intracellular, but not extracellular material.
Autopsy Findings in Three Patients with von Willebrand Disease Type IIB and Type III: Presence of Atherosclerotic Lesions without Occlusive Arterial Thrombi
Authors: Federici A B , Mannucci P M , Fogato E , Ghidoni P , Matturri L 
Published: July 2018

SummaryIt has been reported that pigs with severe von Willebrand disease (vWd) are protected from spontaneous and diet-induced atherosclerosis, but there are very few studies in human patients. Autopsies were carried out on three patients with vWd (one case with the type IIB variant and two cases with type III, a variant similar to that protecting pigs from atherosclerosis), aged 73, 44 and 52 years at the time of death. Hemorrhagic diathesis was an important cause of death for these patients. Atherosclerosis lesions were found in all patients, though of different extent and localization: severe lesions in all vascular areas in the patient with type IIB, few and slighter in all areas in the two patients with type III, except that in one of them there were moderately severe lesions in the coronary arteries. There was no clinical or pathologic evidence of thrombosis in the coronary arteries or other arteries. These data indicate that severe vWd did not protect completely against the development of atherosclerosis, although it is possible that intensive lifelong treatment with plasma concentrates had a modifying influence in these patients.
Inhibitory Effect of Staphylokinase on Platelet Aggregation
Authors: Suehiro Akira , Oura Yoshio , Ueda Motoo , Kakishita Eizo 
Published: July 2018

SummaryWe investigated the effect of staphylokinase (SAK), which has specific thrombolytic properties, on human platelet aggregation. Platelet aggregation induced with collagen was observed following preincubation of platelets in platelet-rich plasma (PRP) or washed platelet suspension (WP) with SAK at 37° C for 30 min. SAK inhibited platelet aggregation in PRP only at the highest examined concentration (1 x 10-4 g/ml). Although SAK did not inhibit platelet aggregation in WP which contained fibrinogen, it did when the platelets had been preincubated with SAK and plasminogen. The most effective concentration in WP was 1 x 10-6 g/ml. The effect could be inhibited by adding aprotinin or α2-antiplasmin. The highest generation of plasmin in the same preincubation fluid was detected at 1 x 10-6 g/ml SAK. We concluded that SAK can inhibit platelet aggregation in WP by generating plasmin and/or fibrinogen degradation products, but is only partially effective in PRP because of the existence of α2-antiplasmin.
Multicentre Evaluation of Commercial Kit Methods: Plasminogen Activator Inhibitor Activity
Authors: Gram J , Declerck P J , Sidelmann J , Jespersen J , Kluft C 
Published: July 2018

SummaryIn order to study the analytical performance of different commercial kits for determination of plasminogen activator inhibitor (PAI) activity we distributed eight selected split samples to 11 European laboratories experienced with haemostasis testing. Three different laboratories were involved in the production of data from each of the commercial kits tested. A considerable variation of PAI activity results reported from the laboratories testing the same commercial kits was observed. The range of reported results could in individual samples exceed the median value indicating an interlaboratory variation of more than 100%.When we harmonized the results reported from different kits in different laboratories by means of an international standard from National Institute for Biological Standards and Control (NIBSC) we still observed that the results produced by some kits deviated systematically from results produced by other kits. Also, the harmonized results were used to estimate the overall coefficient of variation (CV) of PAI activity determined in various laboratories by different kits. We observed an inverse correlation between the PAI activity level and the CV with a CV of about 10Q% for low PAI activity levels and a CV of about 16% for high PAI activity levels. The high imprecision of the kits in the low concentration range of PAI activity indicates that unspecific factors in plasma may interfere with determination of active PAI. This was confirmed by the evaluation of the results from one of the plasma samples, which was PAI-1 depleted. The laboratories involved in the testing reported for this sample a mean value of 6.1 IU/ml.In conclusion, the currently available kits for determination of PAI activity are not accurate for measurement of PAI-1 in plasma, and the kits give imprecise results particularly at low activity levels.