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  1. Article ; Online: Novel genetic approach to investigate the role of plasma secretory phospholipase A2 (sPLA2)-V isoenzyme in coronary heart disease: modified Mendelian randomization analysis using PLA2G5 expression levels.

    Holmes, Michael V / Exeter, Holly J / Folkersen, Lasse / Nelson, Christopher P / Guardiola, Montse / Cooper, Jackie A / Sofat, Reecha / Boekholdt, S Matthijs / Khaw, Kay-Tee / Li, Ka-Wah / Smith, Andrew J P / Van't Hooft, Ferdinand / Eriksson, Per / Franco-Cereceda, Anders / Asselbergs, Folkert W / Boer, Jolanda M A / Onland-Moret, N Charlotte / Hofker, Marten / Erdmann, Jeanette /
    Kivimaki, Mika / Kumari, Meena / Reiner, Alex P / Keating, Brendan J / Humphries, Steve E / Hingorani, Aroon D / Mallat, Ziad / Samani, Nilesh J / Talmud, Philippa J

    Circulation. Cardiovascular genetics

    2014  Volume 7, Issue 2, Page(s) 144–150

    Abstract: ... in atherosclerosis. sPLA2 activity encompasses several sPLA2 isoenzymes, including sPLA2-V. Although observational ... studies show a strong association between elevated sPLA2 activity and CHD, no assay to measure sPLA2-V ... levels exists, and the only evidence linking the sPLA2-V isoform to atherosclerosis progression comes ...

    Abstract Background: Secretory phospholipase A2 (sPLA2) enzymes are considered to play a role in atherosclerosis. sPLA2 activity encompasses several sPLA2 isoenzymes, including sPLA2-V. Although observational studies show a strong association between elevated sPLA2 activity and CHD, no assay to measure sPLA2-V levels exists, and the only evidence linking the sPLA2-V isoform to atherosclerosis progression comes from animal studies. In the absence of an assay that directly quantifies sPLA2-V levels, we used PLA2G5 mRNA levels in a novel, modified Mendelian randomization approach to investigate the hypothesized causal role of sPLA2-V in coronary heart disease (CHD) pathogenesis.
    Methods and results: Using data from the Advanced Study of Aortic Pathology, we identified the single-nucleotide polymorphism in PLA2G5 showing the strongest association with PLA2G5 mRNA expression levels as a proxy for sPLA2-V levels. We tested the association of this SNP with sPLA2 activity and CHD events in 4 prospective and 14 case-control studies with 27 230 events and 70 500 controls. rs525380C>A showed the strongest association with PLA2G5 mRNA expression (P=5.1×10(-6)). There was no association of rs525380C>A with plasma sPLA2 activity (difference in geometric mean of sPLA2 activity per rs525380 A-allele 0.4% (95% confidence intervals [-0.9%, 1.6%]; P=0.56). In meta-analyses, the odds ratio for CHD per A-allele was 1.02 (95% confidence intervals [0.99, 1.04]; P=0.20).
    Conclusions: This novel approach for single-nucleotide polymorphism selection for this modified Mendelian randomization analysis showed no association between rs525380 (the lead single-nucleotide polymorphism for PLA2G5 expression, a surrogate for sPLA2-V levels) and CHD events. The evidence does not support a causal role for sPLA2-V in CHD.
    MeSH term(s) Alleles ; Case-Control Studies ; Coronary Disease/blood ; Coronary Disease/enzymology ; Coronary Disease/genetics ; Genotype ; Group V Phospholipases A2/blood ; Group V Phospholipases A2/genetics ; Humans ; Isoenzymes/blood ; Isoenzymes/genetics ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide
    Chemical Substances Isoenzymes ; Group V Phospholipases A2 (EC 3.1.1.4) ; PLA2G5 protein, human (EC 3.1.1.4)
    Language English
    Publishing date 2014-02-21
    Publishing country United States
    Document type Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2477394-3
    ISSN 1942-3268 ; 1942-325X
    ISSN (online) 1942-3268
    ISSN 1942-325X
    DOI 10.1161/CIRCGENETICS.113.000271
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  2. Article ; Online: Myocardial uptake of 99mTc-annexin-V and 111In-antimyosin-antibodies after ischemia-reperfusion in rats.

    Sarda-Mantel, Laure / Hervatin, Florence / Michel, Jean-Baptiste / Louedec, Liliane / Martet, Geneviève / Rouzet, François / Lebtahi, Rachida / Merlet, Pascal / Khaw, Ban-An / Le Guludec, Dominique

    European journal of nuclear medicine and molecular imaging

    2008  Volume 35, Issue 1, Page(s) 158–165

    Abstract: ... detected in vivo by using (99m)Tc-annexin-V (ANX). Cardiomyocyte membrane disruption is detected in vivo ...

    Abstract Objectives: Phosphatidylserin exposure on cell surfaces occurs early during apoptosis and is detected in vivo by using (99m)Tc-annexin-V (ANX). Cardiomyocyte membrane disruption is detected in vivo by using (111)In-antimyosin-antibodies (AM). We aimed to determine if ANX and AM allow evaluation of the time-course of these two distinct cell death events after myocardial ischemia-reperfusion.
    Methods: Coronary tying (20 min) followed by reperfusion (IR) was performed in 31 rats. Twelve of the rats were injected with ANX, 11 with AM, and eight with both tracers. Myocardial uptake of tracers was studied 1-2 h, 4 h, or 24 h after IR by scintigraphy (ANX, n = 14) and autoradiography (all cases), and compared to histology and Apostain staining.
    Results: Scintigraphy was positive in all rats 2 h after IR and in three of five rats at 24 h. On autoradiography, ANX activity was intense in myocardial lesions as early as 1 h post-IR, whereas AM activity was mild at 2 h then increased at 4 h post-IR. ANX and AM uptakes evolved from mid-myocardium to endocardial and epicardial regions from 2 h to 24 h post-IR. Apostain staining was significant in myocardial lesions (p < 10(6) compared to six sham-operated rats). On histology, myocardial lesion was characterized by interstitial oedema, myocytes necrosis, and dramatic thinning at 24 h.
    Conclusion: These data suggest that ANX and AM allow temporal and regional evaluations of PS exposure and membrane disruption, respectively, during myocytes death after 20-min myocardial ischemia followed by reperfusion. Also, (i) apoptosis starts very early in injured myocardium, (ii) myocyte necrosis occurs later (3-4 h post-reperfusion), and (iii) most dead cells are removed from mid-myocardium between 6 h and 24 h after reperfusion.
    MeSH term(s) Animals ; Annexin A5/metabolism ; Antibodies, Monoclonal/metabolism ; Apoptosis ; Autoradiography ; Male ; Myocardium/metabolism ; Organometallic Compounds/metabolism ; Organotechnetium Compounds/metabolism ; Phosphatidylserines/metabolism ; Positron-Emission Tomography ; Rats ; Reperfusion Injury/diagnostic imaging ; Reperfusion Injury/metabolism ; Reperfusion Injury/pathology ; Reperfusion Injury/surgery ; Time Factors
    Chemical Substances Annexin A5 ; Antibodies, Monoclonal ; Organometallic Compounds ; Organotechnetium Compounds ; Phosphatidylserines ; technetium Tc 99m annexin V ; imciromab pentetate (3U979E1001)
    Language English
    Publishing date 2008-01
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 8236-3
    ISSN 1619-7089 ; 0340-6997 ; 1619-7070
    ISSN (online) 1619-7089
    ISSN 0340-6997 ; 1619-7070
    DOI 10.1007/s00259-007-0559-2
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  3. Article ; Online: Alcohol consumption and the risk of renal cancers in the European Prospective Investigation into Cancer and Nutrition (EPIC). Wozniak MB, Brennan P, Brenner DR, Overvad K, Olsen A, Tjønneland A, Boutron-Ruault MC, Clavel-Chapelon F, Fagherazzi G, Katzke V, Kühn T, Boeing H, Bergmann MM, Steffen A, Naska A, Trichopoulou A, Trichopoulos D, Saieva C, Grioni S, Panico S, Tumino R, Vineis P, Bueno-de-Mesquita HB, Peeters PH, Hjartåker A, Weiderpass E, Arriola L, Molina-Montes E, Duell EJ, Santiuste C, Alonso de la Torre R, Barricarte Gurrea A, Stocks T, Johansson M, Ljungberg B, Wareham N, Khaw KT, Travis RC, Cross AJ, Murphy N, Riboli E, Scelo G.Int J Cancer. 2015 Oct 15;137(8):1953-66. [Epub 2015 Apr 28]. doi: 10.1002/ijc.29559.

    Jay, Raman / Brennan, P / Brenner / Overvad, K / Olsen, A / Tjønneland, A / Boutron-Ruault, M C / Clavel-Chapelon, F / Fagherazzi / Katzke, V / Kühn, T / Boeing, H / Bergmann, M M / Steffen, A / Naska, A / Trichopoulou, A / Trichopoulos, D / Saieva, C / Grioni, S /
    Panico, S / Tumino, R / Vineis, P / Bueno-de-Mesquita, H B / Peeters, P H / Hjartåker, A / Weiderpass, E / Arriola, L / Molina-Montes, E / Duell, E J / Santiuste, C / Alonso de la Torre, R / Barricarte Gurrea, A / Stocks, T / Johansson, M / Ljungberg, B / Wareham, N / Khaw, K T / Travis, R C / Cross, A J / Murphy, N / Riboli, E / Scelo, G

    Urologic oncology

    2017  Volume 35, Issue 3, Page(s) 117

    Abstract: Epidemiologic studies have reported that moderate alcohol consumption is inversely associated with the risk of renal cancer. However, there is no information available on the associations in renal cancer subsites. From 1992 to 2010, 477,325 men and women ...

    Abstract Epidemiologic studies have reported that moderate alcohol consumption is inversely associated with the risk of renal cancer. However, there is no information available on the associations in renal cancer subsites. From 1992 to 2010, 477,325 men and women in the European Prospective Investigation into Cancer and Nutrition cohort were followed for incident renal cancers (n = 931). Baseline and lifetime alcohol consumption was assessed by country-specific, validated dietary questionnaires. Information on past alcohol consumption was collected by lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazard models. In multivariate analysis, total alcohol consumption at baseline was inversely associated with renal cancer; the HR and 95% CI for the increasing categories of total alcohol consumption at recruitment vs. the light drinkers category were 0.78 (0.62-0.99), 0.82 (0.64-1.04), 0.70 (0.55-0.90), and 0.91 (0.63-1.30), respectively, (ptrend = 0.001). A similar relationship was observed for average lifetime alcohol consumption and for all renal cancer subsites combined or for renal parenchyma subsite. The trend was not observed in hypertensive individuals and not significant in smokers. In conclusion, moderate alcohol consumption was associated with a decreased risk of renal cancer.
    MeSH term(s) Alcohol Drinking ; Female ; Humans ; Kidney Neoplasms ; Male ; Nutritional Status ; Proportional Hazards Models ; Prospective Studies ; Risk Factors
    Language English
    Publishing date 2017-02-01
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1336505-8
    ISSN 1873-2496 ; 1078-1439
    ISSN (online) 1873-2496
    ISSN 1078-1439
    DOI 10.1016/j.urolonc.2016.12.022
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  4. Article ; Online: Multiphase CT angiography perfusion maps for predicting target mismatch and ischemic lesion volumes.

    Chung, Kevin J / Pandey, Sachin K / Khaw, Alexander V / Lee, Ting-Yim

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 21976

    Abstract: The complexity of CT perfusion (CTP) acquisition protocols may limit the availability of target mismatch assessment at resource-limited hospitals. We compared CTP mismatch with a mismatch surrogate generated from a simplified dynamic imaging sequence ... ...

    Abstract The complexity of CT perfusion (CTP) acquisition protocols may limit the availability of target mismatch assessment at resource-limited hospitals. We compared CTP mismatch with a mismatch surrogate generated from a simplified dynamic imaging sequence comprising widely available non-contrast CT (NCCT) and multiphase CT angiography (mCTA). Consecutive patients with anterior circulation acute ischemic stroke who received NCCT, mCTA, and CTP were retrospectively included in this study. An mCTA-perfusion (mCTA-P) dynamic series was formed by co-registering NCCT and mCTA. We simulated an ideal mCTA-P study by down-sampling CTP (dCTP) dynamic images according to mCTA timing. Ischemic core and penumbra volumes were estimated by cerebral blood flow and Tmax thresholding, respectively, on perfusion maps calculated independently for CTP, dCTP, and mCTA-P by deconvolution. Concordance in target mismatch (core < 70 ml, penumbra ≥ 15 ml, mismatch ratio ≥ 1.8) determination by dCTP and mCTA-P versus CTP was assessed. Of sixty-one included patients, forty-six had a CTP target mismatch. Concordance with CTP profiles was 90% and 82% for dCTP and mCTA-P, respectively. Lower mCTA-P concordance was likely from differences in collimation width between NCCT and mCTA, which worsened perfusion map quality due to a CT number shift at mCTA. Moderate diagnostic agreement between CTP and mCTA-P was found and may improve with optimal mCTA scan parameter selection as simulated by dCTP. mCTA-P may be a pragmatic alternative where CTP is unavailable or the risks of additional radiation dose, contrast injections, and treatment delays outweigh the potential benefit of a separate CTP scan.
    MeSH term(s) Humans ; Computed Tomography Angiography/methods ; Stroke ; Ischemic Stroke ; Retrospective Studies ; Cerebral Angiography/methods ; Perfusion ; Brain Ischemia ; Cerebrovascular Circulation
    Language English
    Publishing date 2023-12-11
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-48832-9
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  5. Article: (99m)Tc-annexin V and (111)In-antimyosin antibody uptake in experimental myocardial infarction in rats.

    Sarda-Mantel, Laure / Michel, Jean-Baptiste / Rouzet, François / Martet, Geneviève / Louedec, Liliane / Vanderheyden, Jean-Luc / Hervatin, Florence / Raguin, Olivier / Vrigneaud, Jean-Marc / Khaw, Ban An / Le Guludec, Dominique

    European journal of nuclear medicine and molecular imaging

    2006  Volume 33, Issue 3, Page(s) 239–245

    Abstract: Purpose: (99m)Tc-annexin V (ANX) allows scintigraphic detection of apoptotic cells via specific ...

    Abstract Purpose: (99m)Tc-annexin V (ANX) allows scintigraphic detection of apoptotic cells via specific binding to exposed phosphatidylserine. In myocardial infarction, apoptosis of myocytes is variable and depends especially on the presence or absence of coronary reperfusion. In this study, ANX uptake in non-reperfused experimental myocardial infarcts was compared with uptake of a marker of myocyte necrosis ((111)In-antimyosin antibodies, AM) and an immunohistochemical marker of apoptosis (Apostain).
    Methods: The left anterior coronary artery was ligated in 47 Wistar rats, which were then injected with ANX (n=20), AM (n=21) or both (n=6). Myocardial uptake of ANX and AM was determined at 2 h (n=14), 4 h (n=14) and 24 h (n=19) after coronary ligation (CL), by quantitative autoradiography with (n=23) or without (n=24) gamma imaging. Heart-to-lung ratios (HLRs) and infarct-to-remote myocardium activity ratios (INRs) were calculated on the scintigrams and autoradiograms respectively. Cardiac sections were stained with haematoxylin-eosin and Apostain. The above studies were repeated in 12 normal rats.
    Results: All rats with CL showed increased ANX and AM uptake in cardiac areas on scintigrams 24 h after CL, with HLRs higher than in controls: 3.1+/-0.6 versus 1.5+/-0.3 (p=0.001) for ANX and 1.99+/-0.44 versus 1.01+/-0.05 (p<0.0005) for AM. Autoradiography showed intense ANX and AM uptake in infarcts, with comparable topography and INRs at 2 h, 4 h and 24 h after CL (4.6+/-0.9 versus 5.0+/-1.8 at 24 h), while Apostain staining was very low (0.06+/-0.06% of cells).
    Conclusion: In this model of persistent CL, we observed increased ANX uptake in injured myocardium, comparable in intensity, topography and kinetics to that of AM. There was only minimal Apostain staining in the same areas.
    MeSH term(s) Animals ; Annexin A5/pharmacokinetics ; Antibodies, Monoclonal/pharmacokinetics ; Apoptosis ; Heart/diagnostic imaging ; Indium Radioisotopes/pharmacokinetics ; Male ; Metabolic Clearance Rate ; Myocardial Infarction/diagnostic imaging ; Myocardial Infarction/metabolism ; Myocardial Infarction/pathology ; Myocardium/metabolism ; Myocardium/pathology ; Myosins/immunology ; Myosins/pharmacokinetics ; Organotechnetium Compounds/pharmacokinetics ; Radionuclide Imaging ; Radiopharmaceuticals/pharmacokinetics ; Rats ; Rats, Wistar ; Tissue Distribution
    Chemical Substances Annexin A5 ; Antibodies, Monoclonal ; Indium Radioisotopes ; Organotechnetium Compounds ; Radiopharmaceuticals ; technetium Tc 99m annexin V ; Myosins (EC 3.6.4.1)
    Language English
    Publishing date 2006-03
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 8236-3
    ISSN 1619-7089 ; 1619-7070 ; 0340-6997
    ISSN (online) 1619-7089
    ISSN 1619-7070 ; 0340-6997
    DOI 10.1007/s00259-005-1900-2
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  6. Article: Apolipoprotein A-V, triglycerides and risk of coronary artery disease: the prospective Epic-Norfolk Population Study.

    Vaessen, Stefan F C / Schaap, Frank G / Kuivenhoven, Jan-Albert / Groen, Albert K / Hutten, Barbara A / Boekholdt, S Matthijs / Hattori, Hiroaki / Sandhu, Manjinder S / Bingham, Sheila A / Luben, Robert / Palmen, Jutta A / Wareham, Nicholas J / Humphries, Steve E / Kastelein, John J P / Talmud, Philippa J / Khaw, Kay-Tee

    Journal of lipid research

    2006  Volume 47, Issue 9, Page(s) 2064–2070

    Abstract: In mouse models, apolipoprotein A-V (apoA-V) exhibits triglyceride (TG)-lowering effects ... We investigated the apoA-V/TG relationship and the association of apoA-V with coronary artery disease (CAD) risk ... by determining serum apoA-V levels and genotypes in a nested case-control (n = 1,034/2,031) study ...

    Abstract In mouse models, apolipoprotein A-V (apoA-V) exhibits triglyceride (TG)-lowering effects. We investigated the apoA-V/TG relationship and the association of apoA-V with coronary artery disease (CAD) risk by determining serum apoA-V levels and genotypes in a nested case-control (n = 1,034/2,031) study. Both univariate and multivariate apoA-V levels showed no association with future CAD (P = 0.4 and 0.5, respectively). Unexpectedly, there was a significant positive correlation between serum apoA-V and TG in men and women (r = 0.36 and 0.28, respectively, P < 0.001 each) but a negative correlation between apoA-V and LPL mass (r = -0.14 and -0.12 for men and women respectively, P < 0.001 each). The frequency of the c.56C>G polymorphism did not differ between cases and controls despite significant positive association of c.56G with both apoA-V and TG levels. For -1131T>C, the minor allele was significantly associated with lower apoA-V yet higher TG levels and was overrepresented in cases (P = 0.047). The association of -1131T>C with CAD risk, however, was independent of apoA-V levels and likely acts through linkage disequilibrium with APOC3 variants. The positive correlation of apoA-V levels with TG levels, negative correlation with LPL levels, and lack of association with CAD risk highlight the need for further human studies to clarify the role of apoA-V.
    MeSH term(s) Aged ; Apolipoprotein A-V ; Apolipoproteins/blood ; Apolipoproteins/genetics ; Apolipoproteins A ; Case-Control Studies ; Coronary Artery Disease/blood ; Coronary Artery Disease/genetics ; Female ; Gene Frequency/genetics ; Genotype ; Humans ; Linkage Disequilibrium/genetics ; Male ; Middle Aged ; Multivariate Analysis ; Polymorphism, Single Nucleotide/genetics ; Prospective Studies ; Risk Factors ; Triglycerides/blood ; United Kingdom
    Chemical Substances APOA5 protein, human ; Apolipoprotein A-V ; Apolipoproteins ; Apolipoproteins A ; Triglycerides
    Language English
    Publishing date 2006-06-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80154-9
    ISSN 1539-7262 ; 0022-2275
    ISSN (online) 1539-7262
    ISSN 0022-2275
    DOI 10.1194/jlr.M600233-JLR200
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  7. Article ; Online: The Quest of Characterizing Hemodynamic Failure in Patients With Cerebrovascular Disease.

    Khaw, Alexander V / Thiessen, Jonathan D / St Lawrence, Keith / Pandey, Sachin K

    Journal of the American Heart Association

    2023  Volume 12, Issue 24, Page(s) e032657

    MeSH term(s) Humans ; Acetazolamide ; Tomography, X-Ray Computed ; Positron-Emission Tomography/methods ; Cerebrovascular Disorders ; Hemodynamics
    Chemical Substances Acetazolamide (O3FX965V0I)
    Language English
    Publishing date 2023-12-12
    Publishing country England
    Document type Editorial ; Comment
    ZDB-ID 2653953-6
    ISSN 2047-9980 ; 2047-9980
    ISSN (online) 2047-9980
    ISSN 2047-9980
    DOI 10.1161/JAHA.123.032657
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  8. Book ; Thesis: Glykoconjugatmuster während der Entwicklung der menschlichen Wirbelsäule in der Fetalperiode

    Khaw, Alexander V.

    1999  

    Author's details vorgelegt von Alexander V. Khaw
    Language German
    Size 105 Bl., Ill.
    Edition [Mikrofiche-Ausg.]
    Publishing country Germany
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Mainz, Univ., Diss., 1999
    HBZ-ID HT013069281
    Database Catalogue ZB MED Medicine, Health

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  9. Article: Reactions towards organizational change: a systematic literature review.

    Khaw, Khai Wah / Alnoor, Alhamzah / Al-Abrrow, Hadi / Tiberius, Victor / Ganesan, Yuvaraj / Atshan, Nadia A

    Current psychology (New Brunswick, N.J.)

    2022  , Page(s) 1–24

    Abstract: Regardless of the prevalence and value of change initiatives in contemporary organizations, these often face resistance by employees. This resistance is the outcome of change recipients' cognitive and behavioral reactions towards change. To better ... ...

    Abstract Regardless of the prevalence and value of change initiatives in contemporary organizations, these often face resistance by employees. This resistance is the outcome of change recipients' cognitive and behavioral reactions towards change. To better understand the causes and effects of reactions to change, a holistic view of prior research is needed. Accordingly, we provide a systematic literature review on this topic. We categorize extant research into four major and several subcategories: micro and macro reactions. We analyze the essential characteristics of the emerging field of change reactions along research issues and challenges, benefits of (even negative) reactions, managerial implications, and propose future research opportunities.
    Language English
    Publishing date 2022-04-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2021598-8
    ISSN 1936-4733 ; 1046-1310
    ISSN (online) 1936-4733
    ISSN 1046-1310
    DOI 10.1007/s12144-022-03070-6
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  10. Article ; Online: Differences in Stroke Recurrence Risk Between Atrial Fibrillation Detected on ECG and 14-Day Cardiac Monitoring.

    Alvarado-Bolaños, Alonso / Ayan, Diana / Khaw, Alexander V / Mai, Lauren M / Mandzia, Jennifer L / Bogiatzi, Chrysi / Mrkobrada, Marko / Bres-Bullrich, Maria / Fleming, Lorraine A / Lippert, Corbin / Fridman, Sebastian / Sposato, Luciano A

    Stroke

    2023  Volume 54, Issue 8, Page(s) 2022–2030

    Abstract: Background: Ischemic stroke and transient ischemic attack (TIA) standard-of-care etiological investigations include an ECG and prolonged cardiac monitoring (PCM). Atrial fibrillation (AF) detected after stroke has been generally considered a single ... ...

    Abstract Background: Ischemic stroke and transient ischemic attack (TIA) standard-of-care etiological investigations include an ECG and prolonged cardiac monitoring (PCM). Atrial fibrillation (AF) detected after stroke has been generally considered a single entity, regardless of how it is diagnosed. We hypothesized that ECG-detected AF is associated with a higher risk of stroke recurrence than AF detected on 14-day Holter (PCM-detected AF).
    Methods: We conducted a retrospective, registry-based, cohort study of consecutive patients with ischemic stroke and TIA included in the London Ontario Stroke Registry between 2018 and 2020, with ECG-detected and PCM-detected AF lasting ≥30 seconds. We quantified PCM-detected AF burden. The primary outcome was recurrent ischemic stroke, ascertained by systematically reviewing all medical records until November 2022. We applied marginal cause-specific Cox proportional hazards models adjusted for qualifying event type (ischemic stroke versus TIA), CHA₂DS₂-VASc score, anticoagulation, left ventricular ejection fraction, left atrial size, and high-sensitivity troponin T to estimate adjusted hazard ratios for recurrent ischemic stroke.
    Results: We included 366 patients with ischemic stroke and TIA with AF, 218 ECG-detected, and 148 PCM-detected. Median PCM duration was 12 (interquartile range, 8.8-14.0) days. Median PCM-detected AF duration was 5.2 (interquartile range, 0.3-33.0) hours, with a burden (total AF duration/total net monitoring duration) of 2.23% (interquartile range, 0.13%-12.25%). Anticoagulation rate at the end of follow-up or at the first event was 83.1%. After a median follow-up of 17 (interquartile range, 5-34) months, recurrent ischemic strokes occurred in 16 patients with ECG-detected AF (13 on anticoagulants) and 2 with PCM-detected AF (both on anticoagulants). Recurrent ischemic stroke rates for ECG-detected and PCM-detected AF groups were 4.05 and 0.72 per 100 patient-years (adjusted hazard ratio, 5.06 [95% CI, 1.13-22.7];
    Conclusions: ECG-detected AF was associated with 5-fold higher adjusted recurrent ischemic stroke risk than PCM-detected AF in a cohort of ischemic stroke and TIA with >80% anticoagulation rate.
    MeSH term(s) Humans ; Atrial Fibrillation/complications ; Ischemic Attack, Transient/etiology ; Cohort Studies ; Retrospective Studies ; Stroke Volume ; Ventricular Function, Left ; Stroke ; Ischemic Stroke/complications ; Anticoagulants ; Electrocardiography ; Risk Factors
    Chemical Substances Anticoagulants
    Language English
    Publishing date 2023-06-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80381-9
    ISSN 1524-4628 ; 0039-2499 ; 0749-7954
    ISSN (online) 1524-4628
    ISSN 0039-2499 ; 0749-7954
    DOI 10.1161/STROKEAHA.123.043672
    Database MEDical Literature Analysis and Retrieval System OnLINE

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