bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Enoxaparin, Hirulog, and Heparin as Adjunctive Antithrombotic Therapy during Thrombolysis with rtPA in the Stenosed Canine Coronary Artery
Authors: Leadley Robert J , Kasiewski Charles J , Bostwick Jeffrey S , Bentley Ross , McVey Matthew J , White Francis J , Perrone Mark H , Dunwiddie Christopher T 
Published: July 2018

SummaryA canine model of electrolytic injury-induced coronary artery thrombosis and rtPA-induced thrombolysis was used to evaluate the relative antithrombotic efficacy of enoxaparin (a low molecular weight heparin), conventional therapy (heparin or heparin plus aspirin), and hirulog (a direct thrombin inhibitor), when used as adjunctive therapy during thrombolysis. After 60 min of clot aging, adjunctive therapy was begun at doses which elevated APTT approximately 2-fold over baseline. Fifteen minutes after the start of adjunctive therapy, recombinant tissue plasminogen activator (rtPA) was administered (100 μg/kg i.v. bolus + 20 μg/kg/min for 60 min). Adjunctive therapy continued for 1 h after termination of rtPA and blood flow was monitored for two additional hours. Enoxaparin (1 mg/kg i.v. bolus + 30 μg/kg/min, n = 10 for each treatment group) was the only adjunctive treatment that significantly increased the total minutes of flow (143 ± 25 min out of a possible 240 min, vs 54 ± 25 min for vehicle, p <0.05) and decreased thrombus mass (6.0 ± 1.3 mg vs 11.8 ± 3.2 mg for vehicle). Although hirulog (2 mg/kg i.v. bolus + 40 μg/kg/min) did not significantly increase the minutes of flow (120 ± 27 min, p <0.06) or decrease thrombus mass (8.7 ± 1.7 mg) compared to vehicle, these values were not significantly different than those measured in the enoxaparin group. However, the results with hirulog were achieved at the expense of a significantly greater increase in template bleeding time than that measured during enoxaparin treatment. Minutes of flow for heparin (50 U/kg i.v. bolus + 0.6 U/kg/min) and heparin plus aspirin (5 mg/kg i.v. bolus) were 69 ± 20 and 60 ± 23 min, respectively; thrombus masses were 8.2 ±1.3 and 7.3 ±1.0 mg, respectively. In summary, enoxaparin was more effective than conventional therapy in this model in terms of vessel patency and thrombus mass, and was as effective as hirulog, at least at a dose of hirulog that only modestly impaired hemostasis. Therefore, enoxaparin may prove to be a safe and effective alternative agent for adjunctive therapy during thrombolysis with rtPA.
Shunt Dependency Syndrome after Cyst-Peritoneal Shunt Resolved by Keyhole Microsurgical Cyst Resection: Two Case Reports and Literature Review
Authors: Dong Fangyong , Wang Zhen , Li Yakun , Chen Zirong , Zhang Suojun , Wan Feng 
Published: July 2018

Objective Shunt dependency syndrome after cyst-peritoneal (CP) shunt is a rare but serious complication which leads to increased intracranial pressure and neurological deficit. The possible mechanism still remains in controversy. We present our experience on the treatment of the complication and attempt to find a better therapy strategy for the complication.
Methods Two children with middle fossa arachnoid cysts underwent CP shunt with fixed pressure catheters at an opening pressure of 7 cmH2O and then developed dependency syndrome. Both patients were effectively treated by mini-invasive cyst wall excision with the shunts reserved. The clinical manifestation, radiological findings, treatment methods, and therapeutic outcomes were reviewed retrospectively.
Results The time from shunt surgery to shunt dependency syndrome occurrence was 4 and 2 years, respectively. Computed tomography/magnetic resonance findings of the brain showed remarkably collapsed cysts with normal or small ventricles. Both patients underwent secondary mini-invasive cyst wall excision and shunt catheters were reserved. After the operations, their symptoms were resolved except one case with marginally improved visual impairment.
Conclusion Shunt dependency syndrome is a rare but dangerous complication of CP shunt and should be treated in time. Collapsed and thickened cyst wall intermittent covering the catheter head end, decreased brain compliance due to chronic fibrosis, as well as regression of cerebrospinal fluid absorption could be the pathogenesis. We suggest keyhole resection of the residual cyst wall as an effective and mini-invasive treatment option.
Factor V Leiden and Thermolabile Methylenetetrahydrofolate Reductase in Extreme Old Age
Authors: Rees D C , Liu Y T , Cox M J , Elliott P , Wainscoat J S 
Published: July 2018

SummaryBoth factor V Leiden and the C677T methylenetetrahydrofolate reductase (MTHFR) gene mutation are associated with premature vascular disease, and yet are found at surprisingly high allele frequencies in European populations, 2.7% and 35% respectively. We have investigated the prevalence of these mutations in 87 UK residents over the age of ninety, to look for any evidence of their association with premature death.Five factor V Leiden heterozygotes were found, giving an allele frequency of 2.9%, similar to that in the general UK population. The frequency of the thermolabile C677T MTHFR mutation was 36% with 11% homozygotes, again similar to that in the UK population; these genotypes are in Hardy-Weinberg equilibrium, suggesting that there is not strong selection against the homozygous state. One person was both heterozygous for factor V Leiden and homozygous for the C677T mutation. This study suggests that neither factor V Leiden nor thermolabile MTHFR are risk factors for premature death.
Antithrombotic and Hemorrhagic Effects of DX-9065a, a Direct and Selective Factor Xa Inhibitor: Comparison with a Direct Thrombin Inhibitor and Antithrombin Ill-Dependent Anticoagulants
Authors: Morishima Yoshiyuki , Tanabe Kiyoshi , Terada Yasuko , Hara Tsuyoshi , Kunitada Satoshi 
Published: July 2018

Summary(+)-2S-2-[4-[[(3S)-l-acetimidoyl-3- pyrrolidinyl]oxy]phenyl]-3-[7-amidino-2-naphthyl]propanoic acid hydrochloride pentahydrate (DX- 9065a) is an antithrombin III (AT III)-independent and selective inhibitor of activated blood coagulation factor X (FXa). The aim of the present study was to compare the antithrombotic and hemorrhagic effects of DX-9065a with a direct thrombin inhibitor and AT Ill-dependent anticoagulants in rat models of thrombosis and bleeding.Rats were administered intravenously DX-9065a (0.1-1 mg/kg/h), argatroban (0.1-1 mg/k/h), low molecular weight heparin (25-100 anti- XaU/kg/h), unfractionated heparin (25-100 anti-XaU/kg/h) or Orgaran (30-300 anti-XaU/kg/h) for 1 h. DX-9065a dose-dependently inhibited both thrombus formation and elevation in plasma thrombin-AT III complex (TAT) level in a copper wire-inserted arteriovenous (AV) shunt model in rats. The dose required for 50% inhibition of thrombus formation was 0.27 mg/kg/h. DX-9065a did not prolong transection bleeding time up to 7.78 mg/kg/h. Argatroban and AT Ill-dependent anticoagulants also inhibited both thrombus formation and TAT elevation, but prolonged bleeding time at a slightly higher dose than the effective dose. These results suggest that direct and selective inhibition of factor Xa by DX-9065a is preferable for the treatment of thrombosis in the aspect of lack of compromising primary hemostasis.
Enhancement by Ticlopidine of the Inhibitory Effect on In Vitro Platelet Aggregation of the Glycoprotein IIb/IIIa Inhibitor Tirofiban
Authors: Umemura K , Kondo K , Ikeda Y , Nakashima M 
Published: July 2018

SummaryWe determined the effects of combining the glycoprotein IIb/IIIa inhibitor tirofiban (MK-383, Aggrastat) and ticlopidine on inhibition of ADP-induced platelet aggregation, inhibition of collagen-induced platelet aggregation, and prolongation of bleeding time in 5 healthy male volunteers. The study consisted of 2 periods. In period 1, tirofiban was administered intravenously as a bolus injection at a dose of 5.0 µg/kg for 5 min, then as a continuous infusion at a rate of 0.05 µg/kg/min for 5 h 55 min. In period 2, ticlopidine was given orally at a dose of 200 mg once daily for 4 days, after which tirofiban was administered in the same manner as in period 1, starting 2 h after the last dose of ticlopidine. The percent inhibition of platelet aggregation induced by ADP 5 µM at the end of tirofiban infusion in periods 1 and 2 was 73.6 ± 2.6 and 87.1 ± 5.7% (mean ± SD), respectively. The corresponding values for inhibition of platelet aggregation induced by collagen 2 µg/ml were 45.4 ± 36.1 and 82.8 ± 27.0%, respectively. In contrast, the percent inhibition of platelet aggregation induced by ADP and collagen after treatment with ticlopidine alone was 15.8 ± 20.2 and p ± 4.8%, respectively. Compared with tirofiban alone, the combination of tirofiban and ticlopidine significantly enhanced inhibition of platelet aggregation induced by both ADP and collagen (p <0.02 and p <0.012, respectively). The inhibitory effects of ticlopidine alone were not statistically significant. Tirofiban prolonged bleeding time both in period 1 and in period 2. However, tirofiban and ticlopidine combined did not affect bleeding time. Ticlopidine administration did not alter the pharmacokinetics of tirofiban. In conclusion, at the doses of tirofiban and ticlopidine used in this study, the combination of the two drugs enhanced inhibition of platelet aggregation but did not prolong bleeding time, suggesting that appropriate doses of tirofiban can be used concomitantly with ticlopidine with no further safety concerns but with potential additional clinical effects.
Prothrombin Synthesis in the Adult and Fetal Liver
Authors: Cohen Leon , McKinnell James , Puglisi Vincent , Greco Alba , Nardi Michael , Lee Margaret , Karpatkin Margaret 
Published: July 2018

SummaryPlasma levels of blood coagulation zymogens are lower in the newborn than in the adult, with the lowest levels being in preterm infants. It is not known if the lower coagulation factor levels reflect differences in synthesis, secretion or catabolism.Using a rabbit model we have compared prothrombin synthesis in the fetus and adult. In previous studies we attempted to compare transcription in the adult and fetal liver by extraction of mRNA, immobilization on a membrane and hybridization with a labeled cDNA for rabbit prothrombin. Comparison was impaired by the markedly dissimilar composition of fetal and adult rabbit liver; fetal liver is approximately fifty percent hematopoietic tissue even at term (1). In the present study, to obtain a more meaningful comparison we have employed in situ hybridization to compare directly prothrombin expression in adult and fetal liver. We report here that fetal liver contains more prothrombin mRNA than does adult liver. We have further compared prothrombin levels in protein extracts of adult and fetal liver and found that per microgram of extract, fetal liver contains as much prothrombin as does the adult. We conclude that the lower plasma prothrombin levels in the fetus do not reflect a lower rate of synthesis.
Selective Screening for the Factor V Leiden Mutation: Is it Advisable prior to the Prescription of Oral Contraceptives?
Authors: Schambeck Christian M , Schwender Stefan , Haubitz Imme , Geisen Ulrich E , Grossmann Ralf E , Keller Franz 
Published: July 2018

SummaryThe cumulative thrombotic risk of Factor V (FV) Leiden and oral contraceptives (OC) recommends screening for the mutation. Assuming that a family history of thrombosis increases the patient’s likelihood of bearing FV Leiden, a selective rather than universal screening would be performed. We studied the utility of a family history of thrombosis for screening of FV Leiden before prescription of OC and, furthermore, the utility of screening even if oral contraception is favoured. 101 patients who had their first and single thromboembolic event while using OC were interviewed. 609 women without any history of thromboembolism recruited by gynecologists completed a standard questionnaire. 101 of these women, age-matched and currently using OC, were selected for a case-control study. Regarding patients with previous thromboembolism, a family history in a first-degree relative had a positive predictive value (PPV) of only 14% for FV Leiden. A PPV of 12% was calculated by investigating the 609 thrombosis-free women. Inherited FV Leiden (odds ratio = 4.9) and acquired risk factors (odds ratio = 10.1) were both found to be the most prominent, but independent additional risks. Nevertheless, FV Leiden carriers, both heterozygotes and homozygotes, did not suffer earlier from thromboembolism than patients without the mutation. In conclusion, family history is an unreliable criterion to detect FV Leiden carriers. Screening for factor V Leiden can be worthwhile even if the advantages of oral contraception are higher assessed than the thrombotic risk. Affected women knowing about their additional risk could contribute to the prevention of thrombosis in risk situations.
Human Tissue Factor Pathway Inhibitor Fused to CD4 Binds both FXa and TF/FVIIa at the Cell Surface
Authors: Riesbeck Kristian , Dorling Anthony , Kemball-Cook Geoffrey , McVey John H , Jones Mick , Tuddenham Edward G D , Lechler Robert I 
Published: July 2018

SummaryTissue factor pathway inhibitor (TFPI) is one of the main regulators of the tissue factor (TF) pathway of coagulation. To tether human TFPI to the cell surface, full length or truncated TFPI lacking the third Kunitz domain were fused with domains three and four and the carboxy-termi- nal sequence of human CD4. Constructs were transfected into a mouse fibroblast cell line and individual clones were checked for expression using monoclonal antibodies directed against the first two TFPI Kunitz domains and against CD4. Specific human FXa binding was detected by flow cytometry using an anti-FX polyclonal antibody, and inhibition of FXa proteolytic activity was verified by chromogenic substrate assay using S-2765. In addition, TFPI-CD4-expressing cells, preincubated with FXa, specifically bound human TF-FVIIa complexes as revealed with an anti-human TF polyclonal antibody. No functional difference was observed between full length or truncated TFPI-CD4. These results demonstrate that functionally intact TFPI can be tethered to the cell surface. Genetic manipulation of, for example, endothelial cells leading to the stable expression of TFPI may inhibit the development of coronary artery heart disease following cardiac allotransplantation, and may inhibit thrombosis in the context of xenotransplantation.
Small, Dense LDL Particle Concentration Correlates with Plasminogen Activator Inhibitor Type-1 (PAI-1) Activity
Authors: Väisänen Sari , Baumstark Manfred W , Penttilä Ilkka , Bouchard Claude , Halonen Pirjo , Rankinen Tuomo , Berg Aloys , Rauramaa Rainer 
Published: July 2018

SummaryThe relation between LDL subtractions and fibrinolytic activity was studied in 150 men aged 53 to 63 years. Apolipoprotein B (apoB) concentration in the most dense LDL-5 (r = 0.39, p <0.001) and LDL-6 (r = 0.43, p <0.001) subtractions associated with plasminogen activator inhibitor type-1 (PAI-1) activity. Subjects in the highest LDL-6 apoB tortile had higher PAI-1 (24.7 vs. 13.1 AU/ml, p <0.001) and lower t-PA (0.26 vs. 0.54 IU/ml, p <0.001) activities than men in the lowest tortile. The difference in PAI-1 remained after adjusting for either triglycerides (p = 0.039) or insulin (p = 0.015) with cardiorespiratory fitness as an additional covariate, and history of cardiovascular disease and smoking as factors. In a regression analysis, plasma insulin and LDL-6 apoB, but not plasma triglycerides and body mass index, entered the model, and explained 30.6 and 3.9 % of the variance in PAI-1 activity, respectively. The novel finding of the present study was the independent association between small, dense LDL particles and PAI-1 activity in middle-aged men.
Up-regulation of Tissue Factor Expression by Platelet-derived Growth Factor in Human Vascular Smooth Muscle Cells in Culture
Authors: Xuereb J M , Sié P , Boneu B , Constans J 
Published: July 2018

SummaryHuman vascular smooth muscle cells (SMCs) isolated from normal adult arteries were investigated for the expression of Tissue Factor (TF) procoagulant activity at their membrane surface and TF antigen in lysed cells. In growing conditions, SMCs expressed high levels of TF activity and antigen. When cells were made quiescent by 72 h of subculture in serum-poor medium, these levels fell to about one third of the initial values. Platelet-derived growth factor BB (PDGF) up-regulated in a dose-dependent manner TF expression with a significant increase (1.8 fold) within five hours. PD 98059, a specific inhibitor of mitogen-activated protein kinase (MAPK) pathway involved in cell response to PDGF, also prevented TF up-regulation. Short-term treatment by Pentoxifylline and dibutyryl cAMP also completely prevented induced TF up-regulation, but remained without effect on baseline levels of quiescent, unstimulated cells. At their effective concentrations, pentoxifylline and dibutyryl cAMP also inhibited the activation of MAPK induced by PDGF. The rapid induction of TF upon growth factor stimulation may be important in circumstances where SMCs proliferate, such as vascular events or vessel development.
Creation and Use of an Electronic Health Record Reporting Database to Improve a Laboratory Test Utilization Program
Authors: Kurant Danielle , Baron Jason , Strazimiri Genti , Lewandrowski Kent , Rudolf Joseph , Dighe Anand 
Published: July 2018

Objectives Laboratory-based utilization management programs typically rely primarily on data derived from the laboratory information system to analyze testing volumes for trends and utilization concerns. We wished to examine the ability of an electronic health record (EHR) laboratory orders database to improve a laboratory utilization program.
Methods We obtained a daily file from our EHR containing data related to laboratory test ordering. We then used an automated process to import this file into a database to facilitate self-service queries and analysis.
Results The EHR laboratory orders database has proven to be an important addition to our utilization management program. We provide three representative examples of how the EHR laboratory orders database has been used to address common utilization issues. We demonstrate that analysis of EHR laboratory orders data has been able to provide unique insights that cannot be obtained by review of laboratory information system data alone. Further, we provide recommendations on key EHR data fields of importance to laboratory utilization efforts.
Conclusion We demonstrate that an EHR laboratory orders database may be a useful tool in the monitoring and optimization of laboratory testing. We recommend that health care systems develop and maintain a database of EHR laboratory orders data and integrate this data with their laboratory utilization programs.
Adverse Outcomes due to Aggressive Fluid Resuscitation in Children: A Prospective Observational Study
Authors: Muttath Anand , Annayappa Venkatesh Lalitha , Jose Joe , Vasudevan Anil , Ghosh Santu 
Published: July 2018

AbstractFluid management has a major impact on the duration, severity, and outcome of critically ill children. The aim of this study was to examine the relationship between cumulative fluid overload (CFO) with mortality and morbidity in critically ill children. This was a prospective observational study wherein children (1 month–16 years) who were critically ill (with shock requiring inotropes and/or mechanically ventilated) were enrolled. CFO was defined as the sum of daily fluid balances. Daily fluid balance was calculated as a difference between fluid intake (oral and intravenous) and output (urine output, discharge from nasogastric tube) in 24 hours. Percentage of fluid overload (FO) (PFO) was calculated as the ratio of CFO with weight at admission in kilogram. The CFO and PFO at 24, 48, 72 hours and at 7 days or end of PICU stay were calculated. A total of 291 children (244 survivors and 47 non-survivors; 47% males) were included in the final analysis. A higher mortality was observed in children with higher PFO (>20% FO: 45.8% mortality vs. 14.5% < 10% FO, p < 0.01) and CFO (10.97 ± 6.4 mL/kg in survivors vs. 13.95 ± 9.6 mL/kg in non-survivors; p = 0.022) at 72 hours. A 1% increase in fluid overload was associated with 6% and 4% increase in mortality at 72 hours and 7 days, respectively. Similarly, the impact of every 1% increase in fluid overload on both ventilation (yes/no) and acute kidney injury (AKI; yes/no) were found to be significant for both parameters at 72 hours, but only AKI had significant correlation on seventh day. In the multivariate stepwise Cox's proportional hazard model for PICU stay and hospital stay, 3% (p < 0.05) and 2% (p > 0.05) increase were found for every 1% increase in fluid overload, respectively. Oxygenation index is also associated with fluid overload with the adjusted model estimated 0.27 units (95% confidence interval: 0.18–0.36) increase per 1% increase in fluid overload. FO was associated with increased mortality and morbidity in critically ill children.
How do students cope with machine translation output of multiword units? An exploratory study
Authors: Daems Joke , Carl Michael , Vandepitte Sonia , Hartsuiker Robert J. , Macken Lieve 
Published: July 2018

Abstract
In this chapter, we take a closer look at students’ post-editing of multiword units (MWUs) from English into Dutch. The
data consists of newspaper articles post-edited by translation students as collected by means of advanced keystroke
logging tools.
We discuss the quality of the machine translation (MT) output for various types of MWUs, and compare this with the
final post-edited quality. In addition, we examine the external resources consulted for each type of MWU. Results
indicate that contrastive MWUs are harder to translate for the MT system, and harder to correct by the student
post-editors than non-contrastive MWUs. We further find that consulting a variety of external resources helps student
post-editors solve MT problems.
Multiword expressions in multilingual information extraction
Authors: Thurmair Gregor 
Published: July 2018

Abstract
Multilingual Information Extraction requires significant Multiword Expressions (MWE) processing as many such items are
multiwords. The lexical representation of MWEs supports large bilingual lexicons (for Persian, Pashto, Turkish,
Arabic); multiwords are represented like single words, extended by two annotations: MWE head, and lemma plus part of
speech for the MWE parts. In text analysis, MWEs are recognised as part of the parsing process, mot as pre- or
post-processing components. The analysis design extends the X-bar scheme by a level for multiword rules. In transfer,
MWEs are translated as elementary nodes like single word lemmata, to present key concepts for relevance judgement in
Information Extraction. Evaluation shows that 90% of the MWE patterns in the lexicon can be analysed with about 150
MWE-specific rules, and that more than 90% of text document tokens are covered by the proposed integrated single and
multiword processing.
A native origin for Present-Day Englishthey, their, them
Authors: Cole Marcelle 
Published: July 2018

AbstractIt is commonly held that Present-Day Englishthey, their, themare not descended from Old English but derive from the Old Norse third-person plural pronounsþeir, þeira, þeim. This paper argues that the early northern English orthographic and distributional textual evidence agrees with an internal trajectory for the ‘þ-’ type personal pronouns in the North and indicates an origin in the Old English demonstrativesþā, þāra, þām. The Northern Middle English third-person plural pronominal system was the result of the reanalysis from demonstrative to personal pronoun that is common cross-linguistically in Germanic and non-Germanic languages alike.