bluuebunny/crossref_metadata_2025_split huggingface dataset:
Behavioral Economics Interventions in Clinical Decision Support Systems
Authors: Cho Insook , Bates David 
Published: August 2018

Background: Clinical decision support (CDS) systems can improve safety and facilitate evidence-based practice. However, clinical decisions are often affected by the cognitive biases and heuristics of clinicians, which is increasing the interest in behavioral and cognitive science approaches in the medical field.
Objectives: This review aimed to identify decision biases that lead clinicians to exhibit irrational behaviors or responses, and to show how behavioral economics can be applied to interventions in order to promote and reveal the contributions of CDS to improving health care quality.
Methods: We performed a systematic review of studies published in 2016 and 2017 and applied a snowball citationsearch method to identify topical publications related to studies forming part of the BEARI (Application of Behavioral Economics to Improve the Treatment of Acute Respiratory Infections) multisite, cluster-randomized controlled trial performed in the United States.
Results: We found that 10 behavioral economics concepts with nine cognitive biases were addressed and investigated for clinician decision-making, and that the following five concepts, which were actively explored, had an impact in CDS applications: social norms, framing effect, status-quo bias, heuristics, and overconfidence bias.
Conclusions: Our review revealed that the use of behavioral economics techniques is increasing in areas such as antibiotics prescribing and preventive care, and that additional tests of the concepts and heuristics described would be useful in other areas of CDS. An improved understanding of the benefits and limitations of behavioral economics techniques is also still needed. Future studies should focus on successful design strategies and how to combine them with CDS functions for motivating clinicians.
OXYGEN FREE RADICAL-DEPENDENT STEP IN THE CYTOTOXICITY OF DEC-TREATED PLATELETS
Authors: Caebron J Y , Joseph M , Vorng H , Pincemail J , Lagaede M , Capron A 
Published: August 2018

Over the past 35 years, diethylcarbamazine (DEC) has been the most widely used agent for the treatment of filarial diseases. However, in spite of millions of individuals treated, the mode of action of this drug remained unexplained until recently when we reported that the microfilaricidal activity of DEC was mediated by blood platelets with the additional triggering of a filarial excretory antigen (FEA) (Nature, 1987).To set up the mechanism of the larvicidal action of platelets activatedby both DEC and FEA, various inhibitors of the arachidonic acid metabolism were added in the cytotoxic assay. Aspirin failed to modify the platelet activity, whilst nordihydroguaiaretic acid, esculetin, and 5,8,11,14-heneicosatetraynoic acid dose-dependently inhibited the killing of parasites. This relationship suggested the production of a putative cytotoxic lipoxygenase product. Surprisingly, no increase in oxygenated metabolites was noted both by thin layer chromatography and by high pressure liquid chromatography.Thus, we investigated the involvement of oxygen free radicals. The hydroxyl radical scavengers tested (benzoate, uric acid, mannitol, methylene blue... ) more or less inhibited the platelet killing activity. In addition, Fe2 + (down to 10-11M) enhanced the DEC-induced cytotoxicity which was abolished in the presence of the Fe2 + chelator o-phenantroline. Finally, using the electronspin resonance technique it was possible to drop OH radicals from platelets with DMPO, but only in the presence of both DEC and FEA.These results, taken with those concerning the interaction of either IgE/anti-IgE (Nature, 1983, 303, 810-812) or CRP (Science, 1986, 231, 153-156) with platelets, should be regarded as a significant insight into the involvement of platelets in various pathological processes.
PROSTACYCLIN (PGI2) FORMATION IN RELATION TO ANAPHYLATOXIN C5a GENERATION DURING RABBIT ENDOTOXIN SHOCK
Authors: Rampart M , Bult H , Herman A G , Jose P J , Williams T J 
Published: August 2018

Injection of endotoxin (LPS) in animals, a model for gram-negative septic shock, leads to intravascular activation of the complement system, and is one of the few conditions in which 6-oxo-PGF]CX and thromboxane (TX) B2 (non-enzymic metabolites of PGI2 and TXA2) can be detected in arterial blood. Previously we reported associations between complement activation, PGI2 biosynthesis and LPS-induced hypotension in rabbits. As C5a and C5adesArg trigger endothelial PGI2 formation in vitro, we have now measured the plasma levels of immunoreactive (ir) C5a in relation to generation of PGI2 and changes in arterial blood pressure in LPS shock. Pentobarbitone anaesthethized rabbits received LPS (E. coli 0111:B4, 0.5 mg/kg) or
saline via the marginal ear vein. A catheter in the left carotid artery was used to collect blood and to monitor mean arterial blood pressure (MABP). Platelet and leukocyte numbers, haemolytic complement titre (CH50), and plasma ir6-oxo-PGFioc , irTXB2 and irC5a were measured 15 min before and at different times after saline or LPS injection. LPS caused a dose- and time-dependent formation of irC5a in rabbit serum in vitro, predominantly via the classical pathway. LPS also activated complement in vivo, as indicated by about 20 % reduction of CH50 titre (measured after 3h) and a marked increase of arterial irC5a (20-120 ng/ml) in the first 2 to 5 min. After 30 min, irC5a had returned to baseline levels (< 2-5 ng/ml) and remained so up to 3h after injection of LPS. This irC5a peak correlated with a shortlasting initiation of PGI2 release (from < 20 pg/ml up to 550 pg/ml) and a drop in MABP (from about 95 mmHg to 50 mmHg) 2-5 min after LPS. None of these changes occurred after saline injection.In conclusion, LPS activates complement in vivo with concomitant formation of C5a. This peptide may trigger -either directly or after phagocyte activation - endothelial PGI2 biosynthesis, leading to arterial hypotension. This is supported by the suppression of the initial rise of arterial ir6-oxo-PGF1α and hypotension in complement-depleted rabbits. Inhibition of C5a formation or activity may prove to be a meaningful approach to the treatment of septic circulatory shock.
HEPARIN BINDING TO ENDOTHELIAL CELLS POTENTIATES THROMBINSTIMULATED PGI2 PRoDUCTION
Authors: Bårzu T , Molho P , Cariou R , Tobelem G , Caen J 
Published: August 2018

We studied the consequences of hepari n (H) binding to endothel iaI cells (EC) on their basal and thrombin-stimulated PGI2 production. Primary cultures of human umbilical vein EC were incubated with different H concentrations, in serum free medium for 5 hrs. The amount of 6-keto-pGF1α was measured in the medium after 5 hrs with an enzyme-linked inmunoassay. At all concentrations used (0.75 to 75 μg/ml) H did not alter the 5-hour basal production of PGI2 (control, 10.1 α 1.4 ng/106 cells; H 15 μg/m1 ; 10.8 ± 2.7 ng/106 cells). Basal or thrombin (0.1 U/m])-rtimulated (10 min) pGI2 production was then determined using EC bearing only bound heparin. The low, unstimulated PGI2 release (0.412 ± 0.04 ng/106 cells) was not significantly changed in the presence of bound H, but the thrombin-stimulated release was potentiated.The KD for H binding to EC is 2.5 μg/ml. Thus at 3 μg/ml, half maximal saturation of binding sites and maximal potentiation of thrombin action were achieved. This concentration of bound H shifted the dose-response curve of thrombin induced PGI2 production to the left. Similar effect was obtained with half maximal saturating concentration of low molecular weight H (CY 222). Neither arachinodate nor LC4-induced PGI2 release were modified by H binding to EC, suggesting that potentiation is specific to thrombin. Since bound H was shown to not modify the high affinity thrombin binding to EC, the potentiating effect of bound H could related rather to interference with the specific mechanism of thrombin-stimulation of PGI2 production.
A NEW FUNCTION OF HUMAN KININOGENS: THE AMINO-TERMINAL REGION OF DOMAIN 1 INVOLVES AN EF HAND-LIKE STRACTURE FOR METAL BINDING
Authors: Higashiyama S , Ohkubo I , Ishiguro H , Sasaki M 
Published: August 2018

Two types of kininogens in mammalian plasma, high molecular weight (HMW) and low molecular weight (LMW) kininogens, are the precursors of kinin. Especially, HMW kininogen circulates in the plasma as a complex with prekallikrein and factor XI, and functions as a cofactor in the initial phase reactions of intrinsic blood coagulation cascade. Recently, it has been found that the kininogens have inhibitory activity toward cysteine proteinases. The heavy chain portion, which is identical for HMW and LMW kininogens, is composed of three domains, domain 1, 2 and 3. Each the domain 2 and 3 has a reactive site as a cysteine proteinase inhibitor. However, physiological function of domain 1 remains still unknown. By using the antibody recognizing the interaction between HMW kininogen and Ca2+ (anti-HMW kininogen-Ca2+ antibody) as a probe, we newly found the Ca2+ binding site in the domain 1.Anti-HMW kininogen-Ca2+ antibody was isolated from anti-HMW kininogen antiserum as an antibody which bound to a HMW kininogen-Sepharose column equilibrated with 40 mM Tris-HCl buffer, pH 7.5, containing 1.0 M NaCl and 1 mM CaCl2, and was eluted with 3 mM EDTA. Resulting from the characterization by ELISA, this antibody specifically recognized the CB-1 region (CNBr-cleavage fragment 1: 1-160 amino acid sequence) of the heavy chain of kininogen molecules in the presence of Ca2+ or Mg2+. Furthermore, circular dichroism (CD) experiments showed that the conformational changes of HMW kininogen and heavy chain were induced by the addition of metal ions such as Ca2+ or Mg2+, and that this change was due to the conformational change of the CB-1 region. The dissociation constant (Kd) for heavy chain measured by Ca2+ titration analysis by CD at 214 nm was found to be 0.33 ± 0.09 mM. The number of Ca2+ binding sites of heavy chain calculated from Hill plot was 1.15 ± 0.04. The EF handlike structure found in the amino-terminal portion of the heavy chain of kininogen molecules strongly supported the above data. This indicates a possibility that kininogens play an important role as a Ca2+ binding protein.
EXPRESSION OF HUMAN FIBRINOGEN Aa CHAIN cDNA MUTANTS, TO STUDY THE ACCELERATION OF TISSUE PLASMINOGEN ACTIVATOR (t-PA) INDUCED PLASMIN FORMATION
Authors: Koopman Jaap , Lord Susan T , Haverkate F 
Published: August 2018

The capacity to accelerate t-PA induced plasminogen activation, is located on the Aa chain of fibrinogen.To determine more closely which parts of the Aa chain are involved in the accelerating activity, a number of deletion mutants were constructed using the cloned cDNA. The exact sequence of the mutated cDNA's was determined, using the dideoxy sequencing method according to Sanger et al. Plasmids containing the complete Aa cDNA or the constructed mutants were expressed in E. Coli cells. After treatment with thrombin, the cell lysates showed fibrinopeptide A levels ranging from 40 ng/ml to 200 ng/ml. Western Blotting of the cell lysates, using a monoclonal antibody which reacts specifically with the N-terminal part of the Aa chain of human fibrinogen (Koppert et al., Blood, 66, 503-507, 1985), showed protein bands of the molecular size as predicted by the DNA structure. The complete Aa chain expressed in E. Coli was equally effective in the acceleration of plasmin formation as Aa chain isolated from purified fibrinogen.Using a number of deletion mutants we showed that the accelerating capacity is associated with amino acids within the Aa stretch 44-199, which is in agreement with previous studies (Nieuwen-huizen, Biochim. Biophys. Acta, 748, 86-92, 1983). This result shows that the approach using molecular biology seems promising for further defining the site(s) involved in the acceleration of t-PA induced plasminogen activation.
AUTOLOGOUS ENDOTHELIAL SEEDING OF DACRON AORTIC BIFURCATION GRAFTS RESULTS IN DECREASED PLATELET ACCUMULATION
Authors: Örtenwall P , Wadenvik H , Kutti J , Risberg B 
Published: August 2018

Autologous endothelial seeding (AES) of vascular prostheses has been found to reduce thrombogenicity in dogs. In the present study, we evaluated the capability of AES to reduce platelet deposition on vascular prostheses in humans.One limb of an aortic Dacron bifurcation graft was seeded with autologous endothelial cells (EC), harvested from the distal portion of the saphenous vein by enzymatic treatment. The other graft limb was sham-seeded with culture medium, and was used as control. The deposition of Indium-111 labeled platelets was studied 1, 4 and 12 months after surgery. In 17 out of 20 patients, AES resulted in decreased accumulation of radiolabeled platelets, compared to control limbs (p < 0.002), when studied 1 month after surgery. A general reduction in platelet accumulation on vascular prostheses occurred during the first year after surgery. During this observation period a significant difference persisted (p < 0.01), in favor of seeded graft limbs.Although the seeding density was low (400-5000 EC/cm2), the observed reduction in platelet deposition for AES-treated graft limbs merits further investigation of this technique in humans.
LOCALIZATION OF FUNCTIONAL DOMAINS ON HUMAN PLATELET GP Ib-IX COMPLEX BY EPITOPE ANALYSIS WITH MONOCLONAL ANTIBODIES
Authors: Berndt M C , Du X , Beutler L , Booth W J , Castaldi P A 
Published: August 2018

There is now considerable evidence that glycoprotein (GP) Ib plays an important functional role in the von Willebrand factor (vWF)-dependent adhesion of platelets to exposed vascular subendothelium and in the a-thrombin activation of platelets, and that GP IX is important for quinine/quinidine drug-dependent antibody platelet recognition. GP Ib (Mr = 170 KD) consists of two disulfide-linked subunits, Iba (Mr = 135 KD) and Ibβ (Mr = 25 KD), and exists as a heterodimer complex with GP IX (Mr = 22 KD). In this study we have used a panel of 10 antiGP Ib-IX complex monoclonal antibodies to define the functional domains on this complex. Immunoprecipitation of trypsin-treated GP Ib-IX complex revealed that the monoclonal antibodies mapped into three distinct groups: FMC 25, AK 1 and SZ 1, epitopes on the membrane-associated fragment (GP IX and an ≃25 KD remnant of the α-chain disulfide linked to the β-chain); AK 3 and WM 23, epitopes on the central macroglycopeptide core (90 KD); AN 51, SZ 2, AK 2, AP 1 and HIP 1, epitopes on peptide tail (45 KD). Crossblocking studies indicated that with the exception of AK 1 and SZ 1, the monoclonal antibodies were directed against distinct epitopes. All five monoclonal antibodies directed against the peptide tail region blocked ristocetin-dependent vWF-platelet interaction whereas the other five monoclonal antibodies were without effect, indicating that the 45 KD peptide tail region at the plasma end of the α-chain of GP Ib contained the vWF binding domain. Similarly, only the three monoclonal antibodies directed against the membrane-associated region interfered with drug-dependent antibody-platelet interaction.By western blot analysis, α-thrombin bound to the 45 KD peptide tail region. However, only AP 1 interfered significantly with the α-thrombin-dependent aggregation of platelets. This panel of epitope-defined monoclonal antibodies should be of value in further defining the structure-function relationships of this important membrane complex.
PREHOSPITAL CORONARY THROMBOLYSIS: A NEW STRATEGY IN ACUTE MYOCARDIAL INFARCTION
Authors: Teddy Weiss A , Fine David G , Applebaum David , Welber Sima , Sapoznikov Dan , Lotan Chaim , Mosseri Morris , Hasin Yonathan , Gotsman Meryyn S 
Published: August 2018

Thirty-four patients with acute myocardial infarction were treated prospectively using a new strategy of pre-hospital intravenous streptokinase given by a physician-operated mobile intensive care unit. Prehospital treated patients who had experienced no previous myocardial infarction were compared to a similar group treated with streptokinase in-hospital. All patients underwent cardiac catheterization on day 6.Patients receiving streptokinase in the pre-hospital phase of acute myocardial infarction had smaller infarcts and better residual myocardial function than the group given streptokinase in-hospital in terms of peak creatine phosphokinase (900 v.1298 IU, p=0.023), ejection fraction (62 v. 55%, p=0,004), computer-derived dysfunction index (427 v. 727, p=0.003), and electrocardiographic QRS score (4.1 v. 6.4, p=0.001). The only difference between these groups at baseline was the duration of pain prior to initiation of streptokinase therapy (1.0 ± 0.4 hours vs. 1.9 ± 0.9 hours). There were no major complications related to pre-hospital administration of streptokinase.Pre-hospital stretokinase infusion is feasible, safe and practical. It reduces ischemia time because treatment is not delayed until hospital arrival and therapy limits infarct size. Thrombolytic therapy for acute myocardial infarction can be initiated at home and should not be limited to hospitalized patients.
CARDIAC ENZYME RELEASE AFTER FIBRINOLYTIC THERAPY WITH INTRAVENOUS (i.v.) APSAC OR INTRACORONARY (i.e.) STREPTOKINASE IN ACUTE MYOCARDIAL INFARCTION
Authors: Bonnier J J R M , de Swart J B R M , Hoffmann J J M L 
Published: August 2018

The release of CK, CK-MB and ASAT in patients with acute myocardial infarction (AMI) was studied on the relation to reperfusion. In a randomized trial 85 patients with proven AMI entered the study. The occlusion of the infarct related vessel and reperfusion were all assessed angiographically. Fibrinolytic therapy with anisoylated plasminogen streptokinase activator complex (APSAC) i.v. or with streptokinase (SK) i.e. was started within 4 (mean 2.4) hours of the onset of symptoms. 42 were treated with a single i.v. injection over 3-5 min. of APSAC (30U) and 43 with an i.e. infusion over 60 min. of SK (250.000U). Reperfusion was assessed angiographically at 90 min. after the start of treatment. Blood samples were taken before and every 4 hours after dosing up to 24 hours. 74 patients were evaluable for this analysis. The results are:Conclusion: a statistically significant difference (p < .05)** between the reperfused and non reperfused patients could only be demonstrated for the peak value of CK in the APSAC group and of CK-MB in the SK group.*On behalf of the Dutch Invasive Reperfusion Study Group.
PROGNOSTIC VALUE OF SPONTANEOUS PLATELET AGGREGATION IN SURVIVORS OF MYOCARDIAL INFARCTION DURING FOUR YEARS FOLLOW UP
Authors: Trip M D , Manger Cats V , Vreeken J 
Published: August 2018

Platelet aggregation has been implicated in the pathogenesis of atherosclerosis and its complications. We studied the prognostic value of the presence of spontaneous platelet aggregation (SPA) after myocardial infarction in 165 patients during a four years follow up period. Shortly after infarction 78 (47%) showed SPA and 87 (53%) showed no SPA. There were no differences in sex, age, infarct size or localisation and subsequent treatment between both groups. Patients in the SPA-positive group remained predominantely positive and patients in de SPA-negative group negative during the entire follow up period.In the SPA-positive group 25(32%) cardiac events (12 × cardiac death, 13× non fatal recurrent infarction) occurred.In the SPA-negative group 13(15%) cardiac events ( 5× cardiac death, 8× non fatal recurrent infarction) occurred (p < 0.01)In conclusion: the presence of spontaneous platelet aggregation after myocardial infarction is associated with a higher risk for fatal or non fatal recurrent myocardial infarction.
BLOOD TAURINE AFTER MYOCARDIAL INFARCTION
Authors: Sills T H , Heptinstall S 
Published: August 2018

Taurine, an amino acid that is present in high concentrations in the heart, is released from the heart after myocardial damage. There is evidence that the concentration of taurine in whole blood is raised after myocardial infarction (MI), and it has been suggested that blood taurine may be a measure of the degree of infarction. We have obtained serial measurements of blood taurine in patients admitted to a coronary care unit and have compared the results with those obtained for two cardiac enzymes (AST and HBD) and other blood parameters.The patients were divided into two groups: those for whom there was a peak of AST activity (> 40 i.u./l) (Group 1, n = 24) and those for whom AST and HBD was not raised (Group 2, n = 15). For Group 1 patients, mean results were obtained for each of the parameters for the day on which AST peaked (designated Day 0) and for preceeding and subsequent days. For Group 2 a single mean was obtained. Results marked * in the table differ significantly (p < 0.05 or lower) from those for Group 2:It can be seen that blood taurine was significantly raised after MI and followed a pattern similar to the neutrophil count. Furthermore, several positive correlations (r = 0.63-0.79) were obtained between taurine and neutrophil count in both groups, but not between taurine and AST or HBD.In another investigation we measured the amounts of taurine in neutrophils, platelets and plasma from patients with MI (n = 5) and controls (n = 9). We found no differences in the amounts present per neutrophil, per platelet or per ml of plasma.Our data suggest that the increased level of taurine in blood after MI merely reflects the increased number of neutrophils present in blood following the event.
Thrombolytic Properties of Pro-Urokinase, Plasminogen Proactivator (PPA)
Authors: Iga Y , Tanaka K , Tsukada M , Kameyama S , Morichi S , Suyama T 
Published: August 2018

Thrombolytic properties of highly purified plasminogen proactivator (PPA) isolated from culture medium of human kidney cells were compared with those of human urinary urokinase(u-UK). When 125-I-PPA or u-UK was added to whole blood perfusion medium containing preformed thrombi made from whole blood by Chandler loop method, the rates of uptake by the thrombi of PPA and u-UK for 4 hrs were only 2.5% and 2.7% respectively. Using the same thrombi and perfusion medium, an in vitro thrombolytic effect of PPA was examined over a 4 hr period. In early perfusion time, a lag phase was observed in the lysis-time curve of PPA, but not of u-UK. After the lag phase, the lysis by PPA increased linearly without early reaching a low level plateau that was characteristic of the lysis by u-UK. At 4hr, the PPA percent lysis was higher than the u-UK figure. Half lives in rabbit of 125-I-labelled PPA and u-UK iv doses were 5.1±0.2 min and 7.3±0.2 min respectively.The thrombolytic ability of PPA in vivo was evaluated in rabbit pulmonary embolism induced by iv 125-I-fibrin suspension as well as cynomolgus monkey femoral vein thrombosis produced by formation of 125-I-fibrinogen labelled clot in an isolated segment of the vein. In both models, PPA was as effective in thrombolysis as u-UK. However conversion to active UK form, consumptions of plsminogen and PI, fibrinogenolysis and prolongation of APTT in plasma were minor in the PPA group, but not in the u-UK group. It is thus suggested that PPA may cause a local activation limited on the fibrin to lead to a lysis of the thrombi without incurring systemic fibrinolysis