bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicentre evaluation of the Boehringer Mannheim/Hitachi 911 Analysis System
Authors: Zaman Z. , Blanckaert N. , Cobbaert Ch. , Gillery P. , Hagemann P. , Luthe H. , Motta R. , Patrono D. , Jionsué M.-A. , Torralba A. , Castiñeiras M. J. , Fuentes-Arderiu X. , Bablok W. , Domke I. , Stockmann W. 
Published: March 2007

The analytical performance and practicability of the Boehringer Mannheim (BM)/Hitachi 911 analysis system have been assessed in a multicentre evaluation, which involved six laboratories from European countries. Analytes commonly used in classical clinical chemistry were tested in a core programme, which mainly followed the ECCLS guidelines. In addition, a satellite programme covered other analytes, such as proteins, drugs and urine analytes. In total, the study comprised more than 100 000 data items collected over a three‐month period. The evaluation was supported with ‘Computer Aided Evaluation’ (CAEv) and telecommunications.Acceptance criteria for the results were established at the beginning of the study. Nearly all of the analytes met the imprecision limits: within‐run imprecision (as CVs) was 2% for enzyme and substrate assays, 1% for ISE methods and 5% for immunoassays; between‐day imprecision was 3l% for enzyme and substrate assays, 2% for ISE methods and 10% for immunoassays.No relevant drift effects (systematic deviation ≥ 3%) were observed over eight hours. The methods were linear over a wide range. Sample‐related and reagent‐dependent carry‐over can be reduced to a negligible amount by integration of a softwarecontrolled wash‐step.Endogenous interferences were found for creatinine (Jaffé method) and uric acid assays (caused by bilirubin), for creatine kinase, creatine kinase MB isoform and γ‐glutamyltransferase (caused by haemoglobin), and for immunoglobulin A (caused by lipaemia)Accuracy was checked by an interlaboratory survey, recovery studies in control materials and method comparison studies. The survey showed that, with the exception of cholesterol and iron in two laboratories, the recovery of analytes did not deviate by more than 5%. Sixty‐six of the 77 method comparisons performed met the acceptance criteria. The deviations of the remaining 11 results could be explained by differences in either calibration, application or by the use of different methods.Practicability was assessed using a questionnaire which covered all of the important aspects of an analysis system in the clinical laboratory. Twelve groups of attributes out of 14 were rater higher for the BM/Hitachi 911 than for the present situation in the laboratories concerned. Especially high scores were given for the versatility group.The acceptance criteria for the analytical performance of the BM/Hitachi 911 analysis system were fulfilled in all laboratory segments with few exceptions. The practicability exceeded the requirements in most of the attributes. The results of the study confirmed the usefulness of the system as a consolidated workstation in small‐ to medium‐sized clinical laboratories and in STAT laboratories, or as an instrument for special analytes like proteins and drugs, or for urinalysis in large laboratories.
Laboratory automation: a challenge for the 1990s
Authors: Mordini Claude 
Published: March 2007

There is tremendous pressure on industry and laboratories to develop
increasingly complex procucts: for example catalysts, chiral
chemicals, drugs and ceramics; conform to regulations; cope with
increasingly severe competition; and meet steadily increasing costs.
It is difficult, in this situation, to remain productive and competitive.
It is vital to be equipped with, and be able to use appropriately,
all the suitable methodologies and technologies. Working methods
and personnel have to be appropriate. The future depends on three
interdependent domains: automation in the broadest sense of the
word, instrumentation and information systems. The easy work
has already been done. Between 1984 and 1990, it was a question
of going from nothing to something; now, it is necessary to increase
and optimize.Therefore, the crucial question is now: ‘how can we go
quicker in experimentation and acquire more knowledge,
while spending less money?’ One solution is to use all
the aspects of automation (robotics, instrumentation, data).
Successful laboratory automation depends.on: shortened time to
market; improved efficiency/cost ratio; motivation/competence/
expertise; communication; and knowledge acquisition. This paper
examines some of the major technological areas of application.
The trials and tribulations of a robotic screening core
Authors: Babiak John , Lucotch Brian , Russo Anthony , Heydt Linda , Williams Sharon , McCaully Ronald 
Published: March 2007

It is well recognized within the pharmaceutical industry that high
throughput screening is a valuable and rapid tool to identify novel chemical compounds that may lead to tomorrow′s drugs. High throughput screening involves testing as many chemical compounds as quickly as possible against a defined molecular or cellular ‘target’ (for example an enzyme) in the hope that interacting compounds
may provide significant therapeutic benefits.At Wyeth‐Ayerst Research, a Robotics and Automation Research Core Group has been established which serves as the in‐house resource for high throughput screening. The robotics group has three missions: (1) develop and perform high throughput screens
for customers in all therapeutic departments in the company;
(2) educate customers in issues related to screen design; and (3) help
customers to bring automated workstations into their laboratories. The mission, therefore, requires the effective use of automation, as well as building a strong collaboration with customers.The challenges that have been faced fall into two categories: technology limiting and customer relations. Technological challenges arise because it is necessary to develop and implement assays with very different formats and biochemical endpoints within extremely
shortened time frames. The primary means to meet these challenges is with flexible robotics and flexible people. Challenges in the area of customer relations include setting realistic expectations, maintaining a sense of collaboration (and not merely service),
educating investigators as to how to deal with the huge amount of data generated and seeking feedback. Effective and frequent communication, and an awareness of each individual′s perspective, are essential to provide the most appropriate service.
Development and analytical performance of an automated screening method for cannabinoids on the Dimension clinical chemistry system
Authors: Obzansky D. M. , Gorman E. G. , Kramer S. P. , Masulli I. S. , Nuzzaci E. A. , Skogen W. F. 
Published: March 2007

A fully automated, random access method for the determination of cannabinoids (UTHC) was developed for the Dimension AR and XL clinical chemistry systems. The method utilizes Abuscreen ONLINE reagents and a multianalyte liquid calibrator containing 11‐nor‐Δ9‐THC‐9‐carboxylic acid. Within‐run and total reproducibility, determined using NCCLS protocol EP5‐T2, was less than 0.6% and 1.6% CV, respectively, at all concentrations. Calibration stability was retained for at least 30 days. An extensive evaluation of non‐structurally related drugs and various physiological substances indicated lack of interference in the method. No sample carry‐over was observed following a specimen containing 1886 ng/ml 11‐nor‐Δ9‐THC‐9‐carboxylic acid. A 99.1% agreement (N = 445 samples) was found between an EMIT based method on the aca discrete clinical analyser and the Dimension UTHC method.Dimension clinical chemistry system and aca discrete clinical analyser are registered trademarks of Dade International.
Activation of endothelial cells, coagulation and fibrinolysis in children with Dengue virus infection
Authors: Seksarn Panya , Pongsewalak Sureeporn , Thisyakorn Usa , Lusher Jeanne , Sosothikul Darintr 
Published: March 2007

SummaryDengue virus causes a febrile illness: Dengue fever (DF), and less frequently a life-threatening illness: Dengue hemorrhagic fever (DHF). Although severe bleeding remains a major cause of death in DHF, the pathogenesis of bleeding is poorly understood. This prospective cohort study was designed to determine the extent of activation of endothelial cells and the hemostatic system in correlation with clinical severity, and also to detect the best prognostic factor(s) for DHF. Endothelial cell activation, coagulation, anticoagulant and fibrinolysis parameters were measured in 42 children with Dengue infections (20 with DF and 22 with DHF) during three phases of illness. In DHF patients, during the febrile phase, vonWillebrand factor antigen (vWF:Ag),tissue factor (TF) and plasminogen activator inhibitor (PAI-1) were significantly elevated, while platelet counts andADAMTS 13 (a disintegrin and metalloprotease with thrombospondin repeats) were significantly low compared to DF patients. During the toxic phase, soluble thrombomodulin (sTM), tissue plasminogen activator (t-PA) and PAI-1 were also significantly increased, while ADAMTS 13 and thrombin activatable fibrinolysis inhibitor (TAFIa) were significantly low compared to DF patients. Abnormal vWF multimers were seen only in DHF patients. For endothelial cell injury and release of procoagulant components, activation of the coagulation cascade with thrombin generation, increased antifibrinolytic factors and consumption of natural anticoagulants, each appeared to play an important role in the development of hemorrhage in Dengue patients. Using logistic regression analysis, we found plasma VWF:Ag to be the best indicator of progression to DHF.
Genetic strain differences in platelet aggregation and thrombus formation of laboratory rats
Authors: Ito Hideki , Hayashi Hideki , Nagamura Yoshie , Toga Kazuyuki , Yamada Yoshihisa , Sudo Toshiki 
Published: March 2007

SummaryRats are employed to investigate the role of platelets in thrombus formation under flow conditions in vivo and to evaluate the pre-clinical potential of antiplatelet drugs. While Wistar and Sprague-Dawley (SD) strains are commonly used in thrombosis models, a number of rat strains have been established. Each strain possesses genetically unique characteristics such as hypertension, hyperglycemia or hyperlipidemia. The appropriate selection of a strain might have advantages for physiological and pharmacological studies. Comparative investigation of platelet aggregation among laboratory strains of rats is useful for the development of thrombosis models. In the present study, platelet aggregation response in eight laboratory rat strains, ACI, Brown Norway (BN), Donryu, Fischer 344 (F344), LEW, SD, Wistar and WKAH, were compared. Considerable strain differences were observed in ADP-, collagen- and TRAP-induced platelet aggregation. SD and BN are high-platelet-aggregation strains, while F344 and ACI are low-response strains. In the arteriovenous shunt thrombosis model, SD formed larger thrombi than F344 andWistar rats. In the FeCl 3 -induced thrombosis model with the carotid artery, the time to occlusion of SD was significantly shorter than of F344 and ACI rats. F344 and ACI rats had significantly increased bleeding times compared with SD rat. The present study demonstrates that there are considerable strain differences in platelet aggregation among laboratory rats, which reflect thrombus formation.
Tinzaparin and enoxaparin given at prophylactic dose for eight days in medical elderly patients with impaired renal function
Authors: Aghassarian Manvel , Drouet Ludovic , dit-Sollier Claire , Lacut Karine , Heilmann Jean-Jacques , Mottier Dominique , Bergmann Jean-François , Mahé Isabelle 
Published: March 2007

SummaryLow-molecular-weight heparins (LMWHs) accumulate in patients with impaired renal function. As this accumulation depends on heparin chain length and subsequent reticulo-endothelial/renal elimination, LMWHs might have different pharmacodynamic profiles. The primary objective was to examine if any accumulation effect of two LMWHs, enoxaparin and tinzaparin, occurred after repeated administration of a prophylactic dose over eight days in elderly patients (age >75 years) with creatinine clearance between 20 and 50 ml/min and body weight <65Kg. Patients were openly randomized to two groups (enoxaparin 4,000 IU or tinzaparin 4,500 IU once daily). Anti-Xa was measured on day 1 and day 8. Blood samples were taken at 0, 2, 4, 5, 6, 9, 12, 16 and 24 hours. The primary end point was the accumulation factor calculated as a ratio between the maximal anti-Xa activity on day 1and day 8. Fifty-five patients were included (mean age 87.9 ± 5.5 ).The creatinine clearance was 34.7 ± 11.4 ml/min; the body weight was 52.3 ± 8.6 kg. The accumulation factor defined was not significant for tinzaparin (1.05, p=0.29) while it was significantly enhanced for enoxaparin (1.22, p <0.0001). In this pharmacodynamic study performed in elderly patients with impaired renal function, a statistically significant accumulation effect was observed after eight days of prophylactic treatment with enoxaparin but not with tinzaparin, which are two LMWHs with different chain lengths. Trials based on clinical end points should be conducted to evaluate the clinical relevance of these observations.
Factor XIII Val34Leu variant and the risk of myocardial infarction
Authors: Shafey Mona , Anderson Josdalyne , Scarvelis Dimitri , Doucette Steven , Gagnon France , Wells Philip 
Published: March 2007

SummaryGenetic factors are thought to contribute to the pathogenesis of acute myocardial infarction (AMI).A common variant of factor XIII (FXIII), FXIII Val34Leu, may be protective against developing an AMI, but various studies show conflicting results. We performed a meta-analysis to determine whether the FXIII Val34Leu variant is associated with a decreased risk of AMI. One hundred ninety-five articles were reviewed and 12 case-control studies were selected. We included studies involving patients with objectively diagnosed AMIs (WHO criteria), provided that FXIII Val34Leu genotyping data were available. Inclusion decisions, quality assessment, and data extraction were conducted by two reviewers. Hypothesizing that the Leu allele was protective, we performed three analyses with the Val/Val genotype as the reference group. Pooled odds ratios (OR) and their 95% confidence intervals (95% CI) were determined. Prior to pooling, heterogeneity testing was performed using the I 2 statistic. These studies included a total of 8,743 patients, of which 3,663 were AMI patients and 5,080 were healthy controls. Using the random effects methods, protective effects were seen with the Leu/Val genotype alone (OR 0.79, 95% CI 0.68–0.93) and with Leu/Val and Leu/Leu genotypes combined (OR 0.79, 95% CI 0.66–0.93).There was also a protective effect with the Leu/Leu genotype alone, (not statistically significant: OR 0.83, 95% CI 0.61–1.12), likely due to the low frequency of this genotype. These results suggest that there is an association between the factor XIII Leu allele and a modest protective effect against AMI and may provide useful information in profiling susceptibility to myocardial infarction.
Haemostatic activation in post-menopausal women taking low-dose hormone therapy: Less effect with transdermal administration?
Authors: Sheppard Brian , Norris Lucy , Brosnan Jeanette 
Published: March 2007

SummaryHormone therapy (HT) increases the risk of cardiovascular and thromboembolic disease in post-menopausal women. Recent studies have suggested that prothrombotic mechanisms are likely to be involved. Transdermal HT avoids the first-pass effect of oestrogen in the liver and may have a less marked effect on the haemostatic system than equivalent oral preparations. The majority of studies have compared HT preparations that have different formulations as well as routes of administration. We investigated changes in the haemostatic system in post-menopausal women using two pharmacologically similar HT preparations, which differed only in their route of administration. Three hundred forty-four healthy post-menopausal women were randomised to six months treatment with either a transdermal matrix patch containing 25 µg 17 β -estradiol/125 µg norethisterone acetate (NETA) applied every 3–4 days, or an equivalent oral preparation (estradiol 1mg and NETA 0.5 mg given once daily). Oral treatment significantly reduced fibrinogen (p<0.003), factor VIIc (FVIIc) (p<0.00001), and antithrombin (AT) levels (p<0.005); the effects in the transdermal group were less marked with no reduction in fibrinogen levels and lesser effect on FVIIc (p<0.03) compared with oral treatment. Treatment type significantly affected fibrinolysis with lower plasminanti- plasmin (PAP) levels in the transdermal group (p<0.003) and lower plasminogen activator inhibitor-1 antigen (PAI-1) (p<0.012) and tissue plasminogen activator (tPA) antigen levels in the oral group (p<0.002). Prothrombin fragment 1.2 and activated protein C (APC) resistance were not affected by either treatment. Transdermal HT has a less marked effect on coagulation than an equivalent oral preparation. Randomised trials are required to investigate whether this translates into less risk of cardiovascular and thromboembolic disease.
Altered von Willebrand factor subunit proteolysis and multimer processing associated with the Cys2362Phe mutation in the B2 domain
Authors: Marco Luigi , Gallinaro Lisa , Sztukowska Maryta , Mazzuccato Mario , Battiston Monica , Pagnan Antonio , Ruggeri Zaverio , Casonato Alessandra 
Published: March 2007

SummaryThe normal von Willebrand factor (vWF) multimer pattern results from the ADAMTS-13 cleavage of the Tyr1605-Met1606 bond in the A2 domain of vWF. We identified a patient with severe von Willebrand disease (vWD) homozygously carrying a Cys to Phe mutation in position 2362 of vWF with markedly altered vWF multimers and an abnormal proteolytic pattern. The proband’s phenotype was characterized by a marked drop in plasma vWF antigen and ristocetin cofactor activity, and a less pronounced decrease in FVIII. The vWF multimers lacked any triplet structure, replaced by single bands with an atypical mobility, surrounded by a smear, and abnormally large vWF multimers. Analysis of the plasma vWF subunit's composition revealed the 225 kDa mature form and a single 205 kDa fragment, but not the 176 kDa and 140 kDa fragments resulting from cleavage by ADAMTS-13.The 205 kDa fragment was distinctly visible, along with the normal vWF cleavage products, in the patient's parents who were heterozygous for the Cys2362Phe mutation. Their vWF levels were mildly decreased and vWF multimers were organized in triplets, but also demonstrated abnormally large forms and smearing. Our findings indicate that a proper conformation of the B2 domain, which depends on critical Cys residues, may be required for the normal proteolytic processing of vWF multimers.
Protein disulphide isomerase-mediated LA419– NO release provides additional antithrombotic effects to the blockade of the ADP receptor
Authors: Vilahur Gemma , Pena Esther , Padró Teresa , Badimon Lina 
Published: March 2007

SummaryDespite the proven efficacy of current antithrombotic therapy in preventing ischemic heart disease (IHD), vascular events still occur. Our aims were i) to evaluate if combined oral treatment of clopidogrel and LA419, a novel nitric oxide donor with antiischemic and antiplatelet properties, provides additional antiplatelet effects to those of the blockade of P2Y12 receptor; and ii) to gain insight into the mechanism behind LA419 antiplatelet effects. Pigs (n=16) were randomized into four groups: 1) placebocontrol; 2) LA419; 3) clopidogrel; and 4) LA419+clopidogrel. Both compounds were administered orally: LA419 0.9 mg kg-1 twice daily for 10 days; clopidogrel 10 mg kg-1 day the three last days. Antithrombotic effects were assessed by measuring platelet deposition (PD) triggered by denuded and disrupted vessel wall placed on the Badimon chamber. LA419 effects on platelet aggregation, hemodynamic parameters, and platelet protein expression upon in vitro thrombin stimulation were also evaluated. Total PD on denuded vessels was similarly reduced by all treatments with respect to placebo (p<0.05). However, combination of LA419+clopidogrel largely reduced PD triggered by disrupted vessel wall by 80% versus placebo (p<0.005), 15% versus clopidogrel alone (p<0.01), and 30% versus LA419 alone (p<0.005). All treatments inhibited collagen- and ADP-induced platelet aggregation, and no variations were detected in hemodynamic parameters. Proteomic analysis revealed that LA419 was associated with an increase in membrane protein disulphide isomerase (protein implicated in nitric oxide release).Treatment with LA419 may result in additional antiplatelet effect to that of clopidogrel in addition to restoring impaired endothelial dependent vasodilation without hemodynamic side effects. Further studies in IHD patients seem warranted.
The risk for thromboembolic disease in lupus anticoagulant patients due to pathways involving P-selectin and CD154
Authors: Stamer Kathrin , Vormittag Rainer , Skeate Robert , Wahi Monika , Bugert Peter , Pabinger Ingrid , Panzer Simon 
Published: March 2007

SummaryIndividuals with lupus anticoagulants (LA) are at risk for thromboembolism(TE). Chronic inflammation is an important characteristicin LA patients which may dispose for TE. Platelets play akey role in inflammation and TE. We therefore investigated genepolymorphisms as well as plasma levels of platelet receptors aspredictors of TE in 107 LA patients. We compared 74 patientswith a history of thromboembolic disease (TE+),56 with venousthrombosis (VT), 12 with arterial thrombosis (AT), and six patientswho had both, with 33 LA patients without previousthrombosis (TE-).The P-selectin Pro715 allele was slightly morefrequent inVT (OR=3.167,95 % CI 0.955–10.503;p=0.0594),butno patient with AT had this allele (OR=0.099, 95 % CI0.001–0.790; p=0.0238) which therefore may protect from AT. Plasma levels of P-selectin, collected a median of 35 months(range 2–329 months) after the last thrombotic event, werehigher in patients withVT (p=0.0096) than inTE-,but not withAT(p=0.4713).These high P-selectin levels were not explained bythe P-selectin polymorphism. The CA repeat polymorphism inthe 3’-noncoding region of CD154 was significantly associatedwith the development of AT (OR=4.035, 95 % CI 1.329–12.249;p=0.0138). Plasma levels of CD154 were not significantly differentamong the subgroups. Thus, theThr715Pro polymorphism ofP-selectin and CA repeats of CD154 are differentiating betweenthe risk for VT and AT. Further, soluble P-selectin is elevated inLA patients with previousVT, but its role to predictVT needs to be evaluated in prospective studies.
Sport in Vampire Society
Authors: Heinemann Klaus , Puig Nuria 
Published: March 2007

Despite the impressive array of claims and accomplishments, it is our view that sociologists in general, and sport sociologists in particular, are extremely conservative in the challenges they choose to undertake. Sport sociologists have therefore confined their research activities to only the most obvious phenomena. A wide spectrum of questions, issues and problems numerous theoretically important and questions of practical consequence remain unanswered. In this article we use the results from some of our most recent research concerning sport in vampire society to indicate at least partial answers to some fundamental questions. In an empirical investigation using a questionnaire to 43 vampires (20 male, 23 female) we were able to point out that sport culture in vampire society depends on the specific way of life, nutrition and body existence found in that society. Sport is a mirror of society and the physical conditions of the beings therein. A factor analysis did not support a dichotomy but printed out four dimensions of the meaning of sport in vampire society.