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  • 1
    Language: English
    In: Neuropharmacology, 2012, Vol.62(2), pp.1028-1033
    Description: There is growing interest in understanding the neurobiological foundations of attention. To examine whether attentional processes in a change detection task are modulated by dopamine signalling, we investigated the influence of two polymorphisms, i.e. Val158Met (rs4680) in the catechol-O-methyl transferase ( ) and a variable number of tandem repeats polymorphism (VNTR, rs28363170) in the dopamine transporter ( ). The Met allele, which results in lower enzyme activity and therefore probably enhanced PFC dopamine signalling, was significantly associated with task-performance and modulated executive control: Homozygous Met/Met allele carriers had difficulties when performing a change detection task, particularly showing the greatest difficulties in case cognitive and behavioural flexibility was necessary and the required reaction was not part of the subject’s primary task set. Contrary, no difference between the two genotype groups were evident, when an attentional conflict emerged and attentional control was needed for adequate responding. No association with variation in was observed. The results indicate a dissociation of the prefrontal and striatal dopamine system for attentional control and behavioural flexibility in a change detection task: While prefrontal dopamine turnover seems to modulate performance, putatively via difficulties in set shifting leading to behavioural inflexibility in COMT Met allele carriers, striatal dopamine turnover seems less important in this regard. With respect to other studies examining mechanisms of attentional functions in different paradigms, the results suggest that behavioural flexibility and attentional control as two executive subprocesses are differentially influenced by genetic polymorphisms within the dopaminergic system. This article is part of a Special Issue entitled ‘Post-Traumatic Stress Disorder’. ► COMT genotype differentially affects behavioural flexibility and attentional control. ► Met/Met carriers reveal behavioural rigidity but unaffected attentional control. ► DAT1 genotype does not affect behavioural flexibility and attentional control. ► Dissociation of of striatal . neocortical DA system for executive subprocesses.
    Keywords: Behavioural Flexibility ; Comt Val158met ; Dat1 ; Change Detection ; Attention ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0028-3908
    E-ISSN: 1873-7064
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  • 2
    Language: English
    In: The American Journal of Cardiology, 2011, Vol.108(5), pp.639-643
    Description: The association between circulating levels of cardiac troponins and angiographic severity of coronary artery disease (CAD) has not been studied. We investigated whether there is an association between the level of high-sensitivity troponin T (hs-TnT) and angiographic severity of CAD and whether this association is independent of conventional risk factors, N-terminal pro–brain natriuretic peptide (NT–pro-BNP) and C-reactive protein (CRP). This case–control study included 904 patients with stable CAD (cases) and 412 patients with chest pain but without significant CAD on coronary angiogram (controls). Diagnosis of CAD was confirmed or excluded by coronary angiography. Cardiac TnT was measured with conventional and high-sensitivity assays in parallel using the same plasma sample. In patients with no CAD and in those with 1-, 2-, or 3-vessel disease, hs-TnT levels (median, twenty-fifth to seventy-fifth percentiles) were 0.005 μg/L (〈0.003 to 0.009), 0.006 μg/L (0.003 to 0.011), 0.008 μg/L (0.004 to 0.013), and 0.010 μg/L (0.006 to 0.017), respectively (p 〈0.001). In multivariable analysis adjusting for cardiovascular risk factors and clinical variables including NT–pro-BNP and CRP, hs-TnT was an independent predictor of presence of CAD (adjusted odds ratio 1.30, 95% confidence interval 1.07 to 1.59, p = 0.009). In conclusion, in patients with stable and angiographically proved CAD, hs-TnT level is increased compared to subjects without CAD and correlates with angiographic atherosclerotic extent and burden. The association between increased levels of hs-TnT and presence of CAD was independent of traditional cardiovascular risk factors, NT–pro-BNP, and CRP.
    Keywords: Medicine
    ISSN: 0002-9149
    E-ISSN: 1879-1913
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  • 3
    Language: English
    In: Tetrahedron, 02 December 2014, Vol.70(48), pp.9230-9239
    Description: The spatial magnetic properties (Through Space NMR Shieldings— ) of a variety of porphyrins, hemiporphyrazines and tetraoxo[8]circulenes have been computed, visualized as Iso-chemical Shielding Surfaces ( ) of various size and direction, and were examined subject to the interplay of present (para)-diatropic ring currents [(anti)aromaticity] and influences on the latter property originating from the macrocyclic ring conformation, further annelation and partial to complete hydrogenation of aromatic ring moieties. Caution seems to be indicated when concluding from a single NICS parameter to present (para)diatropic ring currents [(anti)aromaticity].
    Keywords: Porphyrins ; Hemiporphyrazines ; Tetraoxocirculenes ; (Anti)Aromaticity ; Anisotropy Effect ; Theoretical Calculations ; Chemistry
    ISSN: 0040-4020
    E-ISSN: 1464-5416
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  • 4
    Language: English
    In: Journal of the American College of Cardiology, 31 July 2012, Vol.60(5), pp.369-377
    Description: The ISAR-REACT 4 (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment-4) platelet substudy aimed to determine the relevance of high on-clopidogrel treatment platelet reactivity (HPR) in non–ST-segment elevation myocardial infarction patients that received abciximab with unfractionated heparin (UFH) or bivalirudin during percutaneous coronary intervention (PCI). In patients undergoing PCI, HPR has been linked to a higher risk for ischemic events. The influence of HPR on clinical outcomes may differ with regard to the adjunctive antithrombotic treatment administered. In ISAR-REACT 4, bivalirudin treatment showed similar efficacy profiles as compared to abciximab with UFH. The impact of HPR on clinical outcomes in abciximab with UFH versus bivalirudin treated non–ST-segment elevation myocardial infarction patients has never been investigated specifically. A total of 564 patients (274 in abciximab/UFH group vs. 290 in bivalirudin group) were enrolled in this study. Presence or absence of HPR following clopidogrel loading was determined by platelet function testing on a Multiplate analyzer (Verum Diagnostica, Munich, Germany). Per study group and stratified in HPR and no-HPR patients, the 30-day incidence of a combined efficacy endpoint (death, myocardial infarction, urgent target vessel revascularization) was determined. For abciximab with UFH, the incidence of the efficacy endpoint was similar in HPR versus no-HPR patients (9.4% vs. 6.7%; odds ratio: 1.4; 95% confidence interval: 0.6 to 3.5; p = 0.43). For bivalirudin, the incidence of the efficacy endpoint was significantly higher in HPR versus no-HPR patients (22.0% vs. 5.0%; odds ratio: 5.4; 95% confidence interval: 2.4 to 12.1; p 〈 0.0001). For patients with a risk profile similar to the subjects enrolled in this platelet substudy, the impact of HPR on clinical outcomes may depend on the type of adjunctive antithrombotic therapy used during PCI. Further investigations are warranted to clarify whether assessment of platelet function may help tailoring antithrombotic therapy during PCI. (Randomized Comparison of Abciximab Plus Heparin With Bivalirudin in Acute Coronary Syndrome [ISAR-REACT 4]; )
    Keywords: Abciximab ; Bivalirudin ; Clopidogrel ; Medicine
    ISSN: 0735-1097
    E-ISSN: 1558-3597
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  • 5
    Language: English
    In: Journal of the American College of Cardiology, 29 October 2013, Vol.62(18), pp.B248-B248
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jacc.2013.08.1574 Byline: Ilka Ott, Stefanie Schulz, Salvatore Cassese, Robert Byrne, Adnan Kastrati Author Affiliation: (1) Deutsches Herzzentrum, Munchen, Germany (2) Deutsches Herzzentrum, Munich, BAVARIA (3) Deutsches Herzzentrum Munich, Munich, Germany
    Keywords: Medicine
    ISSN: 0735-1097
    E-ISSN: 1558-3597
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  • 6
    In: Circulation, 2011, Vol.124(5), pp.624-632
    Description: BACKGROUND—: Durable polymer coatings have been implicated in mid- and long-term adverse events after drug-eluting stent implantation. A polymer-free dual-drug sirolimus- and probucol-eluting stent and a new generation permanent polymer zotarolimus-eluting stent are recently developed technologies demonstrating encouraging results. METHODS AND RESULTS—: In a clinical trial with minimal exclusion criteria, we randomly assigned 3002 patients to treatment with sirolimus- and probucol-eluting stents versus zotarolimus-eluting stents. The trial was designed to demonstrate noninferiority of the sirolimus- and probucol-eluting stents. The primary end point was the combined incidence of cardiac death, target-vessel–related myocardial infarction, or target-lesion revascularization at 1-year follow-up. Follow-up angiography was scheduled at 6 to 8 months.The sirolimus- and probucol-eluting stent was noninferior to the zotarolimus-eluting stent in terms of occurrence of the primary end point (13.1% versus 13.5%, respectively, Pnoninferiority=0.006; hazard ratio=0.97, 95% confidence interval, 0.78 to 1.19; Psuperiority=0.74). The incidence of definite/probable stent thrombosis was low in both groups (1.1% versus 1.2%, respectively; hazard ratio=0.91 [95% confidence interval, 0.45 to 1.84], P=0.80). With regard to angiographic efficacy, there were no differences between the sirolimus- and probucol-eluting stent and the zotarolimus-eluting stent in terms of either in-segment binary angiographic restenosis (13.3% versus 13.4% respectively; P=0.95) or in-stent late luminal loss (0.31±0.58 mm versus 0.29±0.56 mm, respectively; P=0.46). CONCLUSION—: In this large-scale study powered for clinical end points, a polymer-free sirolimus- and probucol-eluting stent was noninferior to a new generation durable polymer-based zotarolimus-eluting stent out to 12 months. CLINICAL TRIAL REGISTRATION—: http://www.clinicaltrials.gov. Unique identifier NCT 00598533.
    Keywords: Medicine ; Anatomy & Physiology;
    ISSN: 0009-7322
    E-ISSN: 15244539
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  • 7
    Language: English
    In: Circulation, March 20, 2012, Vol.125(11), p.1424-1431
    Keywords: Cardiac Patients -- Health Aspects ; Coronary Heart Disease -- Risk Factors ; Coronary Heart Disease -- Care And Treatment ; Fibrinolytic Agents -- Usage ; Hematologic Diseases -- Causes Of
    ISSN: 0009-7322
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  • 8
    Language: English
    In: Neuropharmacology, August 2012, Vol.63(2), pp.259-265
    Description: Appropriate attention levels are pivotal for cognitive processes, and individual differences in attentional functioning are related to variations in the interplay of neurotransmitters. The attention network theory reflects attention as a non-homogenous set of separate neural networks: alerting, orienting and conflicting. In the present study, the role of variations in , which encodes the NR2B subunit of -methyl- -aspartate (NMDA) receptors, was explored with regard to the regulation of arousal and attention by comparing the efficiency of the three attentional networks as measured with the Attention Network Test (ANT). Two synonymous SNPs in , rs1806201 (T888T) and rs1806191 (H1178H) were genotyped in 324 young Caucasian adults. Results revealed a highly specific modulatory influence of SNP rs1806201 on alerting processes with subjects homozygous for the frequent C allele displaying higher alerting network scores as compared to the other two genotype groups (CT and TT). This effect is due to the fact that in the no cue condition faster reaction times were evident in participants carrying at least one of the rare T alleles, possibly as a result of more effective glutamatergic neurotransmission. The results might be further explained by a dissociation between tonic and phasic alertness modulated by the genotype and by a ceiling effect, meaning that subjects cannot be phasicly alert in excess to a certain level. Altogether, the results show that variations in have to be taken into consideration when examining attentional processes. ► rs1806201 genotypes differentially affect attentional networks. ► C/C carriers show low tonic but unaffected phasic alertness. ► Carrying at least one rare T allele leads to higher tonic alertness. ► Level of tonic alertness is possibly due to more efficient glutamatergic neurotransmission.
    Keywords: Grin2b ; Alertness ; Phasic Alertness ; Glutamate ; Noradrenaline ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0028-3908
    E-ISSN: 1873-7064
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  • 9
    In: The New England Journal of Medicine, 2011, Vol.365(21), pp.1980-1989
    Description: Background The combination of glycoprotein IIb/IIIa inhibitors and heparin has not been compared with bivalirudin in studies specifically involving patients with non–ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention (PCI). We compared the two treatments in this patient population. Methods Immediately before PCI, we randomly assigned, in a double-blind manner, 1721 patients with acute non–ST-segment elevation myocardial infarction to receive abciximab plus unfractionated heparin (861 patients) or bivalirudin (860 patients). The study tested the hypothesis that abciximab and heparin would be superior to bivalirudin with respect to the primary composite end point of death, large recurrent myocardial infarction, urgent target-vessel revascularization, or major bleeding within 30 days. Secondary end points included the composite of death, any recurrent myocardial infarction, or urgent target-vessel revascularization (efficacy end point) and major bleeding (safety end point) within 30 days. Results The primary end point occurred in 10.9% of the patients in the abciximab group (94 patients) and in 11.0% in the bivalirudin group (95 patients) (relative risk with abciximab, 0.99; 95% confidence interval [CI], 0.74 to 1.32; P=0.94). Death, any recurrent myocardial infarction, or urgent target-vessel revascularization occurred in 12.8% of the patients in the abciximab group (110 patients) and in 13.4% in the bivalirudin group (115 patients) (relative risk, 0.96; 95% CI, 0.74 to 1.25; P=0.76). Major bleeding occurred in 4.6% of the patients in the abciximab group (40 patients) as compared with 2.6% in the bivalirudin group (22 patients) (relative risk, 1.84; 95% CI, 1.10 to 3.07; P=0.02). Conclusions Abciximab and unfractionated heparin, as compared with bivalirudin, failed to reduce the rate of the primary end point and increased the risk of bleeding among patients with non–ST-segment elevation myocardial infarction who were undergoing PCI. (Funded by Nycomed Pharma and others; ISAR-REACT 4 ClinicalTrials.gov number, NCT00373451 .) This trial compared the combination of abciximab and unfractionated heparin with bivalirudin in patients with non–ST-segment elevation MI who were undergoing coronary stenting. The two regimens had similar efficacy, but there was more bleeding with abciximab and heparin. An invasive strategy of coronary angiography, with revascularization when appropriate, is recommended for high-risk patients who have an acute coronary syndrome.1,2 Owing to the key role that the rupture of an atherosclerotic plaque, which is highly prothrombotic, plays in the pathogenesis of these syndromes,3 identifying the most appropriate adjunctive antithrombotic therapy before, during, and after percutaneous coronary intervention (PCI) has been the target of extensive research for the past three decades. Abciximab is a glycoprotein IIb/IIIa inhibitor with potent platelet-antiaggregative effects.4 Although the administration of abciximab during PCI was not associated with a clinical benefit in patients in stable . . .
    Keywords: Adult–Drug Therapy ; Aged–Adverse Effects ; Angina Pectoris–Therapeutic Use ; Angioplasty, Balloon, Coronary–Adverse Effects ; Antibodies, Monoclonal–Therapeutic Use ; Anticoagulants–Chemically Induced ; Double-Blind Method–Adverse Effects ; Drug Therapy, Combination–Therapeutic Use ; Female–Adverse Effects ; Hemorrhage–Adverse Effects ; Heparin–Therapeutic Use ; Hirudins–Drug Therapy ; Humans–Mortality ; Immunoglobulin Fab Fragments–Therapy ; Male–Adverse Effects ; Middle Aged–Therapeutic Use ; Myocardial Infarction–Adverse Effects ; Peptide Fragments–Therapeutic Use ; Recombinant Proteins–Antagonists & Inhibitors ; Recurrence–Antagonists & Inhibitors ; Thrombin–Antagonists & Inhibitors ; Abridged ; Antibodies, Monoclonal ; Anticoagulants ; Hirudins ; Immunoglobulin Fab Fragments ; Peptide Fragments ; Recombinant Proteins ; Heparin ; Thrombin ; Bivalirudin ; Abciximab;
    ISSN: 0028-4793
    E-ISSN: 1533-4406
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  • 10
    Language: English
    In: Circulation, Oct 23, 2012, Vol.126(17), p.E276-E277
    Description: To the Editor: We recognize the high value of the Bleeding Academic Research Consortium (BARC) validation study reported by Ndrepepa et al1 in this journal. However, although important, their results should be interpreted within the context of the specific study limitations. As stressed in the accompanying editorial, the newly proposed BARC bleeding definitions rely heavily on …
    Keywords: Angioplasty -- Usage ; Angioplasty -- Patient Outcomes ; Hemorrhage -- Analysis ; Hemorrhage -- Risk Factors ; Coronary Heart Disease -- Care And Treatment ; Coronary Heart Disease -- Patient Outcomes
    ISSN: 0009-7322
    E-ISSN: 15244539
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