bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stability of coagulation assays performed in plasma from citrated whole blood transported at ambient temperature
Authors: Zürcher Manuel , Sulzer Irmela , Barizzi Gabriela , Lämmle Bernhard , Alberio Lorenzo 
Published: January 2008

SummaryMany preanalytical variables affect the results of coagulation assays. A possible way to control some of them would be to accept blood specimens shipped in the original collection tube. The aim of our study was to investigate the stability of coagulation assays in citrated whole blood transported at ambient temperature for up to two days after specimen collection. Blood samples from 59 patients who attended our haematology outpatient ward for thrombophilia screening were transported at ambient temperature (outdoor during the day, indoor overnight) for following periods of time: <1 hour, 4–6, 8–12, 24–28 and 48–52 hours prior to centrifugation and plasma-freezing. The following coagulation tests were performed: PT, aPTT, fibrinogen, FII:C, FV:C, FVII:C, FVIII:C, FIX:C, FX:C, FXI:C,VWF:RCo,VWF:Ag, AT, PC activity, total and free PS antigen, modified APC-sensitivity-ratio, thrombin-antithrombin-complex and D-dimer. Clinically significant changes, defined as a percentage change of more than 10% from the initial value, were observed for FV:C, FVIII:C and total PS antigen starting at 24–28 hours, and for PT, aPTT and FVII:C at 48–52 hours. No statistically significant differences were seen for fibrinogen, antithrombin, or thrombin-antithrombin complexes (Friedman repeated measures analysis of variance).The present data suggest that the use of whole blood samples transported at ambient temperature may be an acceptable means of delivering specimens for coagulation analysis. With the exception of factorV andVIII coagulant activity, and total PS antigen all investigated parameters can be measured 24–28 hours after specimen collection without observing clinically relevant changes.
Construction and functional evaluation of hirudin derivatives with low bleeding risk
Authors: Yuan Bin , Dong Chunna , Yu Hongyang , Wang Lisheng , Zhang Chuanling , Yu Aiping , Wu Chutse 
Published: January 2008

SummaryThe purpose of this study was to design and evaluate hirudin (HIR) derivatives with low bleeding risk. In these derivatives, the factor (F) XIa, FXa, and thrombin recognition peptides (EPR, GVYAR, and LGPR, respectively) were linked to the N-terminus of HIR. The intact derivatives have no anticoagulant activity because of the extension of the N-terminus of HIR. After cleavage by the corresponding coagulation factor that occurs on the activation of the coagulation system and in the presence of the thrombus, its activity is released. This limited the anticoagulant activity of these derivatives to the vicinity of the thrombus, and as a result, systemic bleeding complications were avoided. The definite antithrombotic effect and low bleeding parameters of these derivatives were investigated in rat carotid artery and inferior vena cava thrombosis models. In both models, the three derivatives showed significant antithrombotic effects, indicating that anticoagulant activity could be successfully released in vivo. Moreover, the bleeding parameters of these derivatives were lower than that of HIR as indicated by the values of activated partial thromboplastin time (APTT) and thrombin time (TT). To further assess the safety of these derivatives, bleeding time was measured in a mouse tail-cut model. Although the derivatives had obvious effects on bleeding at a dose of 6 mg/kg, the effect of these derivatives on bleeding was significantly weaker than that of HIR at a dose of 1.5 mg/kg. Thus, the benefit-to-risk profiles of the derivatives were superior to that of HIR.
Congenital disorders associated with platelet dysfunctions
Authors: Nurden Paquita , Nurden Alan T. 
Published: January 2008

SummaryGenetic defects of the megakaryocyte lineage give rise to bleeding syndromes of varying severity. Blood platelets are unable to fulfill their hemostatic function of preventing blood loss on vessel injury. Spontaneous bleeding is mostly mucocutaneous in nature. Most studied are deficiencies of glycoprotein (GP) mediators of adhesion (Bernard-Soulier syndrome) and aggregation (Glanzmann thrombasthenia) which concern the GPIb-IX-V complex and the integrin αIIbβ3, respectively. Defects of primary receptors for stimuli include the P2Y12 ADP receptor pathology. Agonist-specific deficiencies in the platelet aggregation response and abnormalities of signaling pathways are common and lead to trauma-related bleeding. Inherited defects of secretion from storage organelles, of ATP production, and of the generation of procoagulant activity are also encountered. In some disorders, such as the Chediak-Higashi, Hermansky-Pudlak, Wiskott-Aldrich and Scott syndromes, the molecular lesion extends to other cells. In familial thrombocytopenia (FT), platelets are produced in insufficient numbers to assure haemostasis. Some of these disorders affect platelet morphology and give rise to the so-called ‘giant platelet’ syndromes (MYH9-related diseases) with changes in megakaryocyte maturation within the bone marrow and premature release of platelets. Diseases of platelet production may extend to other cells and in some cases interfere with development. Transfusion of platelets remains the most common treatment of severe bleeding, management with desmopressin is common for mild disorders. Substitute therapies are available including rFVIIa and the potential use of TPO analogues for FT. Stem cell or bone marrow transplanation is being used for severe diseases while gene therapy may be on the horizon.
Prophylactic P-selectin inhibition with PSI-421 promotes resolution of venous thrombosis without anticoagulation
Authors: Myers Daniel D. , Wrobleski Shirley K. , Zajkowski Paul J. , Hawley Angela E. , Bedard Patricia W. , Ballard Nicole E. , Londy Frank J. , Kaila Neelu , Vlasuk George P. , Wakefield Thomas W. , Meier Thomas R. , Schaub Robert G. 
Published: January 2008

SummaryP-selectin inhibition has been evaluated as a therapeutic for prevention and treatment of venous thrombosis. In this study, a novel oral small-molecule inhibitor of P-selectin, PSI-421, was evaluated in a baboon model of stasis induced deep vein thrombosis (DVT). Experimental groups included i) primates receiving a single oral dose of 1 mg/kg PSI-421 two days prior and continued six days after thrombosis (n=3); ii) primates receiving a single daily subcutaneous dose of 0.57 mg/kg enoxaparin sodium two days prior and continued six days post thrombosis (n=3); and iii) primates receiving no treatment (n=3).PSI-421 treated primates had greater percent vein reopening and less vein wall inflammation than the enoxaparin and controls at day 6. Microparticle tissue factor activity (MPTFA) was significantly lower in the animals receiving PSI-421 immediately after thrombosis (T+6 hours day 0) suggesting lower potential for thrombogenesis in these animals. PSI-421 also reduced soluble P-selectin levels versus controls at T+6 hours day 0, day 2 and 6. Experimental animals in any group showed no adverse effects on coagulation. This study is the first to demonstrate a reduction in MPTFA associated with vein reopening and reduced vein inflammation due to oral P-selectin inhibition in a baboon model of DVT.
How to optimise clopidogrel therapy? Reducing the low-response incidence by aggregometry-guided therapy modification
Authors: Lask Sebastian , Engelhardt Andreas , Mügge Andreas , Neubauer Horst 
Published: January 2008

SummaryThe inhibitory platelet effect of clopidogrel is insufficient in approximately 5 to 30% of patients. These low responders (LR) face a significantly higher risk of cardiovascular complications. The therapeutic management of LR is still undefined. In the present study, we evaluate a novel therapeutic algorithm to reduce the incidence of clopidogrel resistance. One hundred sixty-one patients on 100 mg ofAspirin co-medication underwent elective coronary stenting and were given an initial dosage of 600 mg clopidogrel, followed by 75 mg clopidogrel daily. 48 h later, the platelet responsiveness was tested with ADP (5–20 μM) stimulation by impedance aggregometry (Chronolog 590). A significant rise in impedance (> 5 Ω after 6 minutes, aggregation index > 65%) was defined as LR. In this subgroup, platelets were stimulated with the selective P2Y12-ADP receptor antagonist 2-MeS AMP. One hundred twenty-three patients were clopidogrel-responders (76.4%) and 38 patients were LR (23.6%). A defect of the ADP-receptor P2Y12 was found in three out of 38 LR (7.9%). Inhibition of platelet aggregation indicating clopidogrel-responsiveness was achieved with either a clopidogrel high-dose regimen (22/38, 57.9%); a repeat loading dose, doubling the maintenance dose) or with an alternative therapy with ticlopidine (8/38 (21.1%); 250 mg twice daily).Thus the incidence of LR was reduced from 23.6% to 5.0%. Our aggregometer–guided therapeutic algorithm reduced the relative percentage of clopidogrel LR by 78.9%.This approach could prove to be helpful in achieving a further decrease in the incidence of clopidogrel resistance.
Targeting phosphoinositide 3-kinase γ to fight inflammation and more
Authors: Barberis Laura , Hirsch Emilio 
Published: January 2008

SummaryThe family of class I phosphoinositide-3-kinase (PI3K) is composed of four lipid kinases involved at multiple levels in innate and adaptive immune responses. Class I PI3Ks are divided into two subclasses, IA and IB, sharing a similar catalytic core. Whereas class IA PI3Ks are primarily activated by receptor tyrosine kinases, the unique element of class IB PI3K (PI3Kγ) is activated by G protein coupled receptors (GPCRs), like chemokine receptors. PI3Kγ is mainly expressed in leukocytes where it plays a significant role in chemotaxis. Here, we report recent advances in the analysis of the role of PI3Kγ in leukocytes and in endothelial cells. Results, derived from studies based on both pharmacological and genetic approaches, confirm PI3Kγ as an attractive target for drug discovery. PI3Kγ specific inhibition has gained increasing attention for the treatment of allergic, autoimmune and inflammatory diseases. Development of inhibitors has already provided series of hits, whose efficacy is currently under scrutiny worldwide.
Inversion of Perceived Direction of Motion Caused by Spatial Undersampling in Two Children with Periventricular Leukomalacia
Authors: Morrone Maria Concetta , Guzzetta Andrea , Tinelli Francesca , Tosetti Michela , Del Viva Michela , Montanaro Domenico , Burr David , Cioni Giovanni 
Published: January 2008

Abstract
We report here two cases of two young diplegic patients with cystic periventricular leukomalacia who systematically, and with high sensitivity, perceive translational motion of a random-dot display in the opposite direction. The apparent inversion was specific for translation motion: Rotation and expansion motion were perceived correctly, with normal sensitivity. It was also specific for random-dot patterns, not occurring with gratings. For the one patient that we were able to test extensively, contrast sensitivity for static stimuli was normal, but was very low for direction discrimination at high spatial frequencies and all temporal frequencies. His optokinetic nystagmus movements were normal but he was unable to track a single translating target, indicating a perceptual origin of the tracking deficit. The severe deficit for motion perception was also evident in the seminatural situation of a driving simulation video game. The perceptual deficit for translational motion was reinforced by functional magnetic resonance imaging studies. Translational motion elicited no response in the MT complex, although it did produce a strong response in many visual areas when contrasted with blank stimuli. However, radial and rotational motion produced a normal pattern of activation in a subregion of the MT complex. These data reinforce the existent evidence for independent cortical processing for translational, and circular or radial flow motion, and further suggest that the two systems have different vulnerability and plasticity to prenatal damage. They also highlight the complexity of visual motion perception, and how the delicate balance of neural activity can lead to paradoxical effects such as consistent misperception of the direction of motion. We advance a possible explanation of a reduced spatial sampling of the motion stimuli and report a simple model that simulates well the experimental results.
Combining Path Analysis with Time-resolved Functional Magnetic Resonance Imaging: The Neurocognitive Network Underlying Mental Rotation
Authors: Ecker Christine , Brammer Michael J. , Williams Steven C. 
Published: January 2008

Abstract
There is strong evidence to suggest that the complex cognitive process underlying mental rotation does not have a discrete neural correlate, but is represented as a distributed neural system. Although the neuroanatomical nodes of this so-called rotation network are well established, there is as yet little empirical evidence to indicate how these nodes interact during task performance. Using an optimized, event-related paradigm, this study aimed to test a previously proposed hypothetical neurocognitive network for mental rotation in female subjects with path analysis, and to examine changes in effective connections across different levels of task difficulty. Path analysis was carried out in combination with a time-resolved functional magnetic resonance imaging (fMRI) analysis in order to relate the observed changes on the network level to changes in specific temporal characteristics of the hemodynamic response function on the level of individual neuroanatomical nodes. Overall, it was found that the investigated sequential model did not provide an adequate fit to the data and that a model with parallel information processing was superior to the serial model. This finding challenges traditional cognitive models describing the complex cognitive process underlying mental rotation by a set of sequentially organized, functionally distinct processing stages. It was further demonstrated that the observed in interregional effective connectivity changes with the level of task demand. These changes were directly related to the time course of the experimental paradigm. The results of path analysis in fMRI should therefore only be interpreted in the light of a specific experimental design and should not be considered as general indicators of effective connections.
Examining a Supramodal Network for Conflict Processing: A Systematic Review and Novel Functional Magnetic Resonance Imaging Data for Related Visual and Auditory Stroop Tasks
Authors: Roberts Katherine L. , Hall Deborah A. 
Published: January 2008

Abstract
Cognitive control over conflicting information has been studied extensively using tasks such as the color-word Stroop, flanker, and spatial conflict task. Neuroimaging studies typically identify a fronto-parietal network engaged in conflict processing, but numerous additional regions are also reported. Ascribing putative functional roles to these regions is problematic because some may have less to do with conflict processing per se, but could be engaged in specific processes related to the chosen stimulus modality, stimulus feature, or type of conflict task. In addition, some studies contrast activation on incongruent and congruent trials, even though a neutral baseline is needed to separate the effect of inhibition from that of facilitation. In the first part of this article, we report a systematic review of 34 neuroimaging publications, which reveals that conflict-related activity is reliably reported in the anterior cingulate cortex and bilaterally in the lateral prefrontal cortex, the anterior insula, and the parietal lobe. In the second part, we further explore these candidate “conflict” regions through a novel functional magnetic resonance imaging experiment, in which the same group of subjects perform related visual and auditory Stroop tasks. By carefully controlling for the same task (Stroop), the same to-be-ignored stimulus dimension (word meaning), and by separating out inhibitory processes from those of facilitation, we attempt to minimize the potential differences between the two tasks. The results provide converging evidence that the regions identified by the systematic review are reliably engaged in conflict processing. Despite carefully matching the Stroop tasks, some regions of differential activity remained, particularly in the parietal cortex. We discuss some of the task-specific processes which might account for this finding.
Seeing Sounds and Hearing Sights: The Influence of Prior Learning on Current Perception
Authors: Ryan Jennifer D. , Moses Sandra N. , Ostreicher Melanie L. , Bardouille Timothy , Herdman Anthony T. , Riggs Lily , Tulving Endel 
Published: January 2008

Abstract
It is well known that previous perceptual experiences alter subsequent perception, but the details of the neural underpinnings of this general phenomenon are still sketchy. Here, we ask whether previous experiences with an item (such as seeing a person's face) leads to the alteration of the neural correlates related to processing of the item as such, or whether it creates additional associative connections between such substrates and those activated during prior experience. To address this question, we used magnetoencephalography (MEG) to identify neural changes accompanying subjects' viewing of unfamiliar versus famous faces and hearing the names of unfamiliar versus famous names. We were interested in the nature of the involvement of auditory brain regions in the viewing of faces, and in the involvement of visual regions in the hearing of names. Evoked responses from MEG recordings for the names and faces conditions were localized to auditory and visual cortices, respectively. Unsurprisingly, peak activation strength of evoked responses was larger for famous versus nonfamous names within the superior temporal gyrus (STG), and was similar for famous and nonfamous faces in the occipital cortex. More relevant to the issue of experience on perception, peak activation strength in the STG was larger for viewed famous versus nonfamous faces, and peak activation within the occipital cortex was larger for heard famous versus nonfamous names. Critically, these experience-related responses were present within 150–250 msec of stimulus onset. These findings support the hypothesis that prior experiences may influence processing of faces and names such that perception encompasses more than what is imparted on the senses.
A pilot randomized controlled trial to evaluate the benefit of the cardiac rehabilitation paradigm for the non-acute ischaemic stroke population
Authors: Lennon Olive , Carey Aisling , Gaffney Niamh , Stephenson Julia , Blake Catherine 
Published: January 2008

Objective: To evaluate risk factor reduction and health-related quality of life following a 10-week cardiac rehabilitation programme in non-acute ischaemic stroke subjects. Design: Single-blinded randomized control trial. Setting: Outpatient rehabilitation. Subjects: Forty-eight community-dwelling ischaemic stroke patients (38 independently mobile, 9 requiring assistance, 1 non-ambulatory) were randomly assigned to intervention or control groups by concealed allocation. Intervention: The trial consisted of a 10-week schedule with measures taken at weeks 1 and 10. Both groups continued usual care (excluding aerobic exercise); intervention subjects attended 16 cycle ergometry sessions of aerobic-training intensity and two stress-management classes. Main outcome measures: Cardiac risk score (CRS); VO2 (mL O2/kg per minute) and Borg Rate of Perceived Exertion (RPE) assessed during a standardized ergometry test; Hospital Anxiety and Depression Scale (HADS); Frenchay Activity Index; Fasting Lipid Profiles and Resting Blood Pressure. Results: Group comparison with independent t-tests showed significantly greater improvement at follow-up by intervention subjects than controls in VO2 (intervention 10.6 ±1.6 to 12.0 ± 2.2, control 11.1 ±1.8 to 11.1 ±1.9 t=4.734, P<0.001) and CRS (intervention 13.4 ±10.1 to 12.4 ±10.5, control 9.4 ±6.7 to 15.0 ±6.1 t=-2.537, P<0.05). RPE rating decreased in intervention subjects (13.4 ±12.2 to 12.4 ±2.0) and increased in controls (13.8 ±1.8 to 14.4 ±1.6); Mann—Whitney U (U = 173.5, P<0.05). Within-group comparison showed significant decrease in the HADS depression subscale in the intervention group alone (5.1 ±3.4 to 3.0 ±2.8) (Wilcoxon signed ranks test Z=-3.278, P<0.001). Conclusion: Preliminary findings suggest non-acute ischaemic stroke patients can improve their cardiovascular fitness and reduce their CRS with a cardiac rehabilitation programme. The intervention was associated with improvement in self-reported depression.
A novel cause of intrathecal baclofen overdosage: lessons to be learnt
Authors: Dalton Catherine , Keenan Elizabeth , Stevenson Val 
Published: January 2008

Case presentation: A serious intrathecal baclofen overdose occurred in a 45-year-old woman with primary progressive multiple sclerosis following a catheter dye study with concomitant change in baclofen concentration. The pump and catheter were emptied of baclofen 2000 μg/mL, refilled and primed with baclofen 1000 μg/mL. No correction was made for the `dead space' between the reservoir and catheter access port, which contained baclofen 2000 μg/mL. Failure of the priming bolus to account for the residual baclofen concentration within the dead space resulted in a serious overdose. Action: Amendments are being made to both our local and the Medtronic protocols. Conclusion: We hope that by reporting this incident the risk of this potentially fatal error re-occurring is minimized.
Switching from serotonin reuptake inhibitors to duloxetine in patients with resistant obsessive compulsive disorder: a case series
Authors: Dell'Osso Bernardo , Mundo Emanuela , Marazziti Donatella , Altamura A Carlo 
Published: January 2008

Obsessive compulsive disorder (OCD) is a chronic disorder, currently recognized as one of the most common psychiatric disorder as well as one of the most disabling of all medical disorders. OCD is characterized by high rates of partial and/or absent response to standard, recommended treatments (serotonin reuptake inhibitors and psychotherapy). Recent investigation showed that Venlafaxine, a dual serotonin and norepinephrine reuptake inhibitor (SNRI), may be a valid alternative for some treatment-refractory patients. We present the cases of four OCD patients with comorbid mood or anxiety disorders, who were treated with serotonin reuptake inhibitors (SRIs) at adequate doses for at least 12 weeks, showing partial/no response. Patients were then switched to Duloxetine up to 120 mg/day and followed up for 12 weeks. Three out of four patients showed a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score reduction ≥35%. Duloxetine may be helpful in patients with treatment-resistant OCD, although larger and controlled studies are warranted to confirm this preliminary observation.