bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paraneoplastische erosive Arthritis, Rheumafaktor- und Anti-CCP-positiv, bei B-Zell-Lymphom
Authors: Matveev I. , Hartig I. , Braun M. 
Published: March 2018

ZusammenfassungWir berichten von einem 73-jährigen Patienten, der sich mit einer symmetrischen poly artikulären Arthritis, primär die MCPund MTP-Gelenke betreffend, vorstellte. Serologisch erhöhtes CRP und Nachweis eines Anti-CCP-Antikörpers und Rheumafaktors. Radiologisch zeigten sich zystisch erosive Veränderungen an den MCP- und MTP-Gelenken. Eine rheumatoide Arthritis wurde diagnostiziert und eine Basistherapie mit MTX, begleitend Prednisolon, eingeleitet. Im Verlauf traten Schmerzen der distalen Tibia auf, in der Knochenszintigrafie zeigte sich eine Mehr belegung, in der CT fiel eine zystisch destruierende Läsion auf. Die Histologie dieser Läsion ergab eine Infiltration eines CD20+-B-Zell-Lymphoms. Paraneoplastische Syndrome müssen immer differenzialdiagnostisch bei neu auftretenden Arthritiden erwogen werden. Die differenzialdiagnostischen Erwägungen paraneoplastischer Syndrome mit Arthritiden werden diskutiert.
Das Laufverhalten von Patienten mit künstlichem Hüftgelenkersatz und dessen Folgeerscheinungen: Ein systematisches Review zum aktuellen Forschungsstand
Authors: Pohl T. , Horstmann T. , Perschke S. 
Published: March 2018

ZusammenfassungLaufen wird als Sportart mit hoher Stoßbelastung eingestuft und Patienten mit einem künstlichen Hüftgelenk nicht empfohlen. Entgegen dieser Empfehlungen kehren einige Läufer nach einer Operation dennoch zum Laufsport zurück. Es sind wissenschaftliche Erkenntnisse zum allgemeinen postoperativen Sportverhalten vorhanden, allerdings kaum Ergebnisse zum Laufen im Speziellen. Auf Basis der aktuellen Datenlage soll dieses Review die Fragen bearbeiten, (1) wie hoch der Läuferanteil unter den Patienten ist, (2) welche Trainingsparameter festzustellen sind und (3) ob negative Folgeerscheinungen für die Prothesenhaltbarkeit auftreten. In PubMed wurde mit einer spezifischen MeSH-Term-Suche gearbeitet. Nach der Analyse von Titel, Abstract und Volltext erfüllten drei von ursprünglich 39 Artikeln die Einschlusskriterien. Postoperativ betrug der Anteil an joggenden Patienten zwischen 3,8 % und 16,3 %. Nur zwei der Studien berichteten von Trainingsparametern: Die wöchentliche Trainingsfrequenz lag bei 3,5–4-Mal pro Woche mit Läufen zwischen 14,4–28,4 km, 116–186 Minuten und 7,7–9,2 km/h. Ein Patient nahm sogar an einem Marathon über 42,5 km teil. In der eingeschlossenen Literatur wurde in keinem Fall von Prothesenlockerung oder erhöhter Abnutzung berichtet. Positiv ist, dass die Läufer eine bessere körperliche Funktion und weniger Schmerzen zeigten als nicht laufende Hüftprothesen-Patienten. Es bleibt zu beachten, dass die eingeschlossene Literatur keine ausreichende Evidenz über Langzeiteffekte auf Hüftgelenkersatz durch Laufen liefert. Erstens ist die Anzahl an Studien mit hoher Qualität gering und zweitens lagen die beobachteten Follow-Up-Längen bei 3,9 Jahren und sind folglich unzulänglich kurz. Neben Longitudinalstudien würde eine biomechanische Untersuchung helfen, die Empfehlungen zum Laufen nach Hüftgelenkersatz weiterzuentwickeln.
Risk of Venous Thromboembolism Recurrence: High Negative Predictive Value of D-dimer Performed after Oral Anticoagulation Is Stopped
Authors: Legnani Cristina , Cosmi Benilde , Guazzaloca Giuliana , Pancani Claudia , Coccheri Sergio , Palareti Gualtiero 
Published: March 2018

SummaryIn some patients with previous venous thromboembolism (VTE) D-dimer levels (D-Dimer) tend to increase after oral anticoagulant therapy (OAT) is stopped. The aim of our study was to evaluate the predictive value of D-Dimer for the risk of VTE recurrence after OAT withdrawal. After a first episode of deep vein thrombosis (DVT) of the lower limbs and/or pulmonary embolism (PE), 396 patients (median age 67 years, 198 males) were followed from the day of OAT discontinuation for 21 months. D-dimer was measured on the day of OAT withdrawal (T1), 3-4 weeks (T2) and 3 months (+/− 10 days, T3) thereafter. The main outcome events of the study were: objectively documented recurrent DVT and/or PE. D-dimer was found to be increased in 15.5%, 40.3% and 46.2% of the patients at T1, T2 and T3, respectively. In 199 (50.2%) patients, D-dimer levels were elevated in at least one measurement. During a follow-up of 628.4 years, 40 recurrences were recorded (10.1% of patients; 6.4% patient-years of follow-up). D-dimer was increased in at least one measurement in 28 of these cases, but remained normal in 11 subjects (three of whom had recurrent events triggered by circumstantial factors, three with malignancyassociated factors) (in one subject D-dimer was not measured). The negative predictive value (NPV) of D-dimer was 95.6% (95% CI 91.6-98.1) at T3 and was even higher (96.7%; 95% CI 92.9-98.8) after exclusion of the six recurrences due to circumstantial factors. Only five idiopathic recurrences occurred in the 186 patients with consistently normal D-dimer. In conclusion, D-dimer has a high NPV for VTE recurrence when performed after OAT discontinuation.
FV HR2 Haplotype as Additional Inherited Risk Factor for Deep Vein Thrombosis in Individuals with a High-Risk Profile
Authors: Bossone Anna , Coalizzo Donatella , D’Andrea Giovanna , Brancaccio Vincenzo , Ciampa Antonio , Grandone Elvira , Di Minno Giovanni , Margaglione Maurizio 
Published: March 2018

SummaryA number of strongly linked polymorphisms within the Factor V gene (FV HR2 haplotype) has been identified as a cause of resistance to activated protein C, and has suggested a modest risk factor for vein thrombosis. We investigated the frequency of the HR2 haplotype in 433 consecutive patients with confirmed deep vein thrombosis and 326 controls. The HR2 haplotype was more frequent in patients (15.2%) than in controls (10.1%). The risk of thrombosis among carriers of this haplotype was significantly increased (odds ratio: 1.6 [95% CI: 1.0-2.5]). The estimated risk associated with the HR2 haplotype was 1.8 (95% CI: 1.1-2.9) in subjects with (n = 255), and 1.4 (95% CI: 0.8-2.4) in those without (n = 178) acquired risk factors for vein thrombosis. After adjustment for sex, FV Leiden and FII A20210 mutations, the estimated risk of vein thrombosis among carriers of the HR2 haplotype was 1.8 (95% CI: 1.1-2.8). Present data indicate that the HR2 haplotype is independently associated with vein thrombosis among individuals with a highrisk profile.
Plasma Protein Oxidation Is Associated with an Increase of Procoagulant Markers Causing an Imbalance between Pro- and Anticoagulant Pathways in Healthy Subjects
Authors: Rocca Bianca , Marchioli Roberto , Landolfi Raffaele , De Cristofaro Raimondo 
Published: March 2018

SummaryThe aim of the present study was to investigate whether the overall oxidation state of plasma proteins is associated with changes of circulating pro- and anticoagulant markers in healthy subjects (n = 99, 49 males, 50 females, aged from 6 to 91 yrs.). The carbonyl content of plasma proteins was measured and validated as an ex vivo index of the overall protein oxidation state due to its correlation with the plasma level of o-tyrosine (r = 0.87, P <0.0001), which is a well known oxidized product of L-phenylalanine. Using a multivariate analysis the carbonyl content of plasma protein was positively associated with procoagulant markers such as prothrombin F1 + 2 (r = 0.28, P = 0.0019) and fibrinopeptide A, (FpA) (r = 0.278, P = 0.003), as well as with the soluble derivative of the endothelial protein thrombomodulin (TM) (r = 0.469, P <0.0001). The procoagulant marker of thrombin activity, FpA, was significantly and positively correlated with the anticoagulant product of thrombin, namely the Protein C activation peptide (PCP), only in the tertile with low protein carbonyl content. At higher tertiles this correlation was no longer observed, thus suggesting a detrimental effect of oxidative stress on the TM/Protein C anticoagulant pathway. In 15 subjects with high carbonyl content of plasma protein, treatment for 18 days with 600 mg/d of vitamin E did not substantially modify the protein carbonyl content, the anticoagulant markers APC/PCP, and all procoagulant markers except F1+2, whose value significantly decreased by 25%.In conclusion, the present study shows that a high plasma protein oxidation ex vivo is associated with an overall hemostatic imbalance, which favors procoagulant markers. Vitamin E treatment in vivo restores only in part the equilibrium between pro- and anticoagulant pathways. This may open the way to further studies aimed at elucidating the mechanisms by which the oxidative stress is linked to activation of the coagulation system in atherothrombotic disorders.
Abbreviations: APC: activated Protein C; F1+2: prothrombin fragment 1+2; FpA: fibrinopeptide A; PCP: Protein C activation peptide; TM: thrombomodulin
Evaluation of Frozen Plasma Calibrants for Enhanced Standardization of the International Normalized Ratio (INR): A Multi-Center Study
Authors: Johnston Marilyn , Adcock Dorothy 
Published: March 2018

SummaryLocal ISI calibration has been proposed to improve INR accuracy and inter-laboratory precision. We evaluated the affect of local PT calibration on INR precision and accuracy using six levels of frozen plasma calibrants prepared and pooled from normal donors and patients stabilized on sodium warfarin (coumarin) based oral anticoagulant therapy (OAT). Reference prothrombin time (PT) and INR values were assigned to these calibrants in accordance with World Health Organization (WHO) procedure using rTF 95 international reference preparation (IRP) of thromboplastin (human recombinant). These calibrants, along with five similarly characterized individual OAT patient plasmas, were distributed to 127 laboratories in a multi-center study. Calibrant plasmas were evaluated and INR’s subsequently determined on the 5 OAT test samples using: 1) the ISI and MNPT in place before the study (the local system), 2) the locally calibrated ISI value (local system with ISI calibration) and 3) a PT-INR calibration curve. Precision of INR results improved across the study group using the local system with ISI calibration and the PT-INR calibration curve methods, while accuracy of INR results improved using the PT-INR calibration curve approach only and not the local ISI calibration. The authors conclude that frozen plasma calibrants can be used locally to enhance precision and accuracy of PT results as reported in INR. These calibrants are effective over a range of reagents and instrument combinations. Furthermore, the PT-INR calibration curve appears to be the superior method for local calibration.
Synergistic Effect of Thrombomodulin Promoter -33G/A Polymorphism and Smoking on the Onset of Acute Myocardial Infarction
Authors: Li Yi-Heng , Tsai Wei-Chuan , Chao Ting-Hsing , Guo How-Ran , Tsai Liang-Miin , Wu Hua-Lin , Shi Guey-Yueh , Chen Jyh-Hong 
Published: March 2018

SummaryThrombomodulin is an endothelial cell surface receptor for thrombin. It plays an important role in the regulation of blood coagulation by decreasing thrombin activity and activating protein C. This study examined the possible association between the thrombomodulin -33G/A polymorphism and acute myocardial infarction. We recruited 278 patients (mean age 57.5 years, 241 men) with documented myocardial infarction and 450 age-and sex-matched control subjects. Polymerase chain reaction and single-strand conformation polymorphism was used to define the thrombomodulin -33G/A polymorphism. The frequency of the thrombomodulin GA+AA genotype among patients with myocardial infarction was higher than that in control subjects (22.7% vs. 16.2%, odds ratio [OR] 1.5, 95% confidence interval [CI] 1.0 to 2.2). The -33G/A polymorphism (GA+AA genotype) was significantly associated with myocardial infarction (OR 1.6, 95% CI 1.1 to 2.5) as was hypertension, diabetes mellitus and smoking. Among young myocardial infarction patients (age ≤45 years, n = 72), the frequency of -33G/A polymorphism was more significantly higher than that in control subjects (29.2% vs. 16.2%, OR 2.1, 95% CI 1.2 to 3.8). The -33G/A polymorphism (OR 2.3, 95% CI 1.3 to 4.1) and smoking (OR 4.5, 95% CI 2.5 to 7.9) were the only independent risk factors for young myocardial infarction. Furthermore, among patients who did not smoke, the polymorphism was associated with a nonsignificant increase in the risk of young myocardial infarction (OR 1.9, 95% CI 0.6 to 5.6); whereas, in the presence of smoking, the increase was statistically significant (OR 2.3, 95% CI 1.2 to 4.7). Smoking carriers of the thrombomodulin -33G/A polymorphism had a nearly 10-fold increased risk of young myocardial infarction (OR 9.8, 95% CI 4.3 to 22.4) when compared with nonsmoking non-carriers. We concluded that there was a significant association between the thrombomodulin -33G/A polymorphism and myocardial infarction in our population, especially in young patients. The clinical effect of this genetic factor was enhanced by smoking.
Short-Term Inhibition of ADP-Induced Platelet Aggregation by Clopidogrel Ameliorates Radiation-Induced Toxicity in Rat Small Intestine
Authors: Wang Junru , Albertson Christopher , Zheng Huaien , Fink Louis , Herbert Jean-Marc , Hauer-Jensen Martin 
Published: March 2018

SummaryEndothelial dysfunction and increased platelet aggregation may be involved in the pathogenesis of normal tissue radiation toxicity. This study assessed clopidogrel, an inhibitor of ADP-induced platelet aggregation, as a modulator of intestinal radiation injury (radiation enteropathy).Rat small intestine was exposed to 21 Gy X-radiation. Clopidogrel (20 mg/kg/day) or vehicle was administered from 2 days before to 10 days after irradiation. Structural radiation injury, neutrophil infiltration, smooth muscle cell proliferation, collagen content, and TGF-β1 expression were assessed 2 weeks (early phase) and 26 weeks (delayed phase) after irradiation, using quantitative histology and immunohistochemistry, morphometry, and real-time fluorogenic probe RT-PCR.Irradiated intestine exhibited significant histopathologic injury, reduced mucosal surface area, vascular sclerosis, intestinal wall fibrosis, increased collagen content, and increased TGF-β1 expression. Clopidogrel reduced ADP-induced platelet aggregation by 93% and significantly attenuated the severity of post-radiation vascular sclerosis (p = 0.004 and p = 0.02) and the loss of mucosal surface area (p = 0.0008 and p = 0.003) at both 2 and 26 weeks. Clopidogrel also ameliorated overall histopathologic injury (p = 0.02), relative intestinal collagen content (p = 0.03), and collagen III immunoreactivity levels 2 weeks after irradiation, and caused a borderline reduction in the radiation-induced increase in extracellular matrix-associated TGF-β immunoreactivity at 26 weeks (p = 0.04). The effects of clopidogrel on steady-state TGF-β1 mRNA levels and neutrophil infiltration were not statistically significant.Short-term clopidogrel administration affords protection against early and, to a lesser extent, delayed radiation enteropathy. Modulation of platelet aggregation should be subject to further studies as a potential method to increase safety and efficacy of radiation therapy.
Human Platelet Gαq Deficiency Is Associated with Decreased Gαq Gene Expression in Platelets but not Neutrophils
Authors: Gabbeta J. , Vaidyula V. R. , Dhanasekaran D. N. , Rao A. K. 
Published: March 2018

SummaryG-proteins play an important role in platelet signal transduction and regulate responses upon activation of G-protein coupled receptors (GPCR). We have previously reported a patient with impaired platelet responses associated with deficiency in platelet Gαq. To understand the molecular basis for this defect, the cDNA sequence encoding Gαq (1080 bp) was obtained by reverse-transcription and polymerase chain reaction of platelet RNA; the cDNA sequence showed no mutations in the patient. Platelet Gαq mRNA levels were decreased by >50% compared to normal subjects; platelet Gαi2 mRNA levels were normal. Neutrophil calcium mobilization and elastase secretion, upon activation with several agonists, and neutrophil Gαq mRNA and protein levels were normal. These studies demonstrate that the patient has a defect in Gαq gene expression in platelets but not neutrophils, possibly due to defects in transcriptional regulation or mRNA stability, and suggest a hematopoietic-lineage specific defect.
Laboratory Diagnosis of Lupus Anticoagulants for Patients on Oral Anticoagulant Treatment
Authors: Chantarangkul Veena , Clerici Marigrazia , Mannucci Pier , Tripodi Armando 
Published: March 2018

SummaryThe detection of lupus anticoagulant (LA) in plasmas from patients on oral anticoagulants is problematic because of their prolonged clotting times. Mixing of patients and normal plasmas prior to testing for LA is employed to overcome this problem. We investigated the diagnostic efficacy of silica clotting time (SCT) and dilute Russell viper venom test (dRVVT) performed at low and high phospholipid concentrations, to diagnose LA in patients on oral anticoagulants, in comparison with Staclot® LA (Stago) performed with and without hexagonal phospholipids and normal plasma. Case materials were 114 filtered plasmas from patients on oral anticoagulants with (n = 62) and without (n = 52) the antiphospholipid syndrome. Plasmas were considered LA-positive when Staclot® LA (taken as the “gold standard”) was diagnostic for LA. Forty-four plasmas were positive with Staclot® LA. Forty and 39 of these were also positive with SCT and dRVVT (sensitivity relative to Staclot® LA was 91% and 89%, respectively). Seventy plasmas were negative with Staclot® LA. Three of these were positive with both SCT and dRVVT (specificity relative to Staclot® LA was 96%). Kappa values for measure of agreement were 0.87 and 0.85 (p <0.001), respectively. In conclusion, SCT and dRVVT performed at low and high phospholipid concentrations without normal plasma can be considered as reliable as Staclot® LA peformed with hexagonal phospholipids and normal plasma to diagnose LA in patients on oral anticoagulants. Advantages of SCT and dRVVT over Staclot® LA are easy automation, no need for normal plasma and relatively low cost.
Effects of Transdermal and Oral Oestrogen Replacement Therapy on C-Reactive Protein Levels in Postmenopausal Women: A Randomised, Placebo-Controlled Trial
Authors: Post M. S. , Stehouwer C. D. A. , van Baal W. M. , Mijatovic V. , Schalkwijk C. G. , Kenemans P. , van der Mooren M. J. 
Published: March 2018

SummaryTo investigate the effect of postmenopausal oral and transdermal hormone therapy on plasma levels of C-reactive protein (CRP), we performed a randomised, double-blind, double-dummy, placebo-controlled, 15-month study. One hundred and fifty-two healthy hysterectomised postmenopausal women received daily either placebo (n = 49), or transdermal 17 β-oestradiol (E2) 50 µg (tE2 group, n = 33), or oral E2 1 mg (oE2 group, n = 37), or oral E2 1 mg combined with gestodene 25 µg (oE2 + G group, n = 33) for thirteen 28-day treatment cycles, followed by four cycles placebo for each group. Data were collected at baseline and in cycles 4, 13 and 17. In cycle 13, CRP was significantly increased in the oE2 group compared to placebo (P = 0.004). The median percentage change from baseline versus placebo was +75% (P <0.001). In cycle 17, significantly lower values were observed in the oE2 group compared to cycle 13 and to the placebo group (-49%, P <0.001). There were no significant changes versus placebo in the other groups. In conclusion, oral E2 significantly increased CRP levels. This change was larger than the increase found during oral E2 + G. Transdermal E2 did not affect CRP levels.
Protein C Deficiency caused by Homozygosity for a Novel PROC D180G Mutation – in vitro Expression and Structural Analysis of the Mutation
Authors: Gedde-Dahl Tobias , Tjønnfjord Geir , Villoutreix Bruno , Brosstad Frank , Lind Bent 
Published: March 2018

SummryHomozygosity for a novel D180G mutation in the protease domain of protein C, associated with plasma protein C activity and antigen levels of 8% of normal was identified in a thrombosis prone family. Transient expression of protein C in HK-293 cells and analysis of protein C antigen in culture media and cell lysates showed that the secretion of mutant protein as compared with wild-type protein was reduced by 79% while the intracellular contents were similar. Computer analysis of the X-ray structure of activated protein C and of a theoretical model of the zymogen predicts that the mutation destabilises the molecule locally. Our results are compatible with a relatively unstable mutant molecule that could be trapped inside the cell and degraded. However, if secreted the mutant molecule could have a relatively normal catalytic activity and structure consistent with the plasma levels of protein C activity and the late onset of thrombosis.
Aurintricarboxylic Acid Attenuates Intimal Thickening after Balloon Injury of the Rabbit Aorta
Authors: Waissbluth Alvaro , Abendschein Dana , Eisenberg Paul , Ghigliotti Giorgio , Schwartz David 
Published: March 2018

SummaryInjury to the arterial wall initiates a cascade of events including platelet deposition and an increase in procoagulant activity of the vessel wall that is associated with intimal thickening and vascular wall remodeling. This study was designed to characterize the effects of aurintricarboxylic acid (ATA), an inhibitor of von Willebrand factor function, on vascular procoagulant activity and the development of intimal thickening after balloon-induced injury to the rabbit aorta.Treatment with ATA, aspirin, or the combination of agents at doses that attenuated platelet aggregation decreased platelet deposition and procoagulant activity bound to the vessel wall after injury. Treatment with ATA reduced the intimal thickening observed 2 weeks after injury. Surprisingly, aspirin treatment had no effect on intimal thickening. These data indicate that inhibition of platelet deposition, while it is able to attenuate local thrombin elaboration, is not alone sufficient to attenuate subsequent intimal thickening that occurs in response to arterial injury.
Overanticoagulation Associated with Combined Use of Antibacterial Drugs and Acenocoumarol or Phenprocoumon Anticoagulants
Authors: Visser Loes , Penning-van Beest Fernie , Kasbergen A. A. , De Smet Peter , Vulto Arnold , Hofman Albert , Stricker Bruno H. 
Published: March 2018

SummarySeveral case reports associated combined use of coumarins and antibacterial drugs with overanticoagulation. Despite the fact that these drugs are frequently prescribed concurrently, there is little quantitative information on the risks of such complications.To study which antibacterial drugs are associated with overanticoagulation during therapy with coumarins.Population-based cohort study in a sample of the Rotterdam Study.All patients who were treated with acenocoumarol or phenprocoumon in the study period from April 1, 1991 through December 31, 1998 and for whom INR data were available.Patients were followed until an INR 2: 6.0, the end of their treatment, death or end of the study period. Proportional hazards regression analysis was used to estimate the risk of an INR 2: 6.0 in relation to concomitant use of an oral anticoagulant and antibacterial drugs after adjustment for several potentially confounding factors such as age, gender, hepatic dysfunction, malignancies, and heart failure.Of the 1124 patients in the cohort, 351 developed an INR 2: 6.0. The incidence rate was 6.9 per 10,000 treatment days. Sulfamethoxazole combined with trimethoprim most strongly increased the risk of overanticoagulation with an adjusted relative risk of 20.1 (95% CI: 10.7-37.9). Stratification showed that the induction period of overanticoagulation varied between different antibacterial drugs.In this study among outpatients of an anticoagulation clinic using acenocoumarol or phenprocoumon, several antibacterial drugs strongly increased the risk of overanticoagulation. Awareness of these drug interactions and more frequent monitoring of INR values during the initial stages of antibacterial drug therapy are warranted to minimize the risk of bleeding complications.