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| 1 | Clopidogrel with aspirin in High- risk patients with Acute Non- disabling Cerebrovascular Events II (CHANCE-2): rationale and design of a multicentre randomised trial显示文摘Background In patients with a minor ischaemic stroke or transient ischaemic attack(TIA),separate trials have shown that dual antiplatelet therapy with clopidogrel plus aspirin(clopidogrel-aspirin)or ticagrelor plus aspirin(ticagrelor-aspirin)are more effective than aspirin alone in stroke secondary prevention.However,these two sets of combination have not been directly compared.Since clopidogrel was less effective in stroke patients who were CYP2C19 loss-of function(LOF)allele carriers,whether ticagrelor-aspirin is clinically superior to clopidogrel-aspirin in this subgroup of patients with stroke is unclear.Aim To describe the rationale and design considerations of the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events(CHANCE-2)trial.Design CHANCE-2 is a randomised,double-blind,double-dummy,placebo-controlled,multicentre trial that compares two dual antiplatelet strategies for minor stroke or TIA patients who are CYP2C19 LOF allele carriers:ticagrelor(180 mg loading dose on day 1 followed by 90 mg twice daily on days 2-90)or clopidogrel(300 mg loading dose on day 1 followed by 75 mg daily on days 2-90),plus open-label aspirin with a dose of 75-300 mg on day 1 followed by 75 mg daily on day 2-21.All will be followed for 1 year.Study outcomes The primary efficacy outcome is any stroke(ischaemic or haemorrhagic)within 3 months and the primary safety outcome is any severe or moderate bleeding event within 3 months.Discussion The CHANCE-2 trial will evaluate whether ticagrelor-aspirin is superior to clopidogrel-aspirin for minor stroke or TIA patients who are CYP2C19 LOF allele carriers. | Yongjun Wang Claiborne Johnston Philip M Bath Xia Meng Jing Jing Xuewei Xie Anxin Wang Yuesong Pan Anding Xu Qiang Dong Yilong Wang Xingquan Zhao Zixiao Li Hao Li | 2021 | Stroke & Vascular Neurology2021,6,2: | 10 |
| 2 | Blood pressure management in acute stroke显示文摘Blood pressure(BP)is elevated in 75%or more of patients with acute stroke and is associated with poor outcomes.Whether to modulate BP in acute stroke has long been debated.With the loss of normal cerebral autoregulation,theoretical concerns are twofold:high BP can lead to cerebral oedema,haematoma expansion or haemorrhagic transformation;and low BP can lead to increased cerebral infarction or perihaematomal ischaemia.Published evidence from multiple large,high-quality,randomised trials is increasing our understanding of this challenging area,such that BP lowering is recommended in acute intracerebral haemorrhage and is safe in ischaemic stroke.Here we review the evidence for BP modulation in acute stroke,discuss the issues raised and look to on-going and future research to identify patient subgroups who are most likely to benefit. | Jason P Appleton Nikola Sprigg Philip M Bath | 2016 | Stroke & Vascular Neurology2016,1,2: | 7 |
| 3 | It is safe to use transdermal glyceryl trinitrate to lower blood pressure in patients with acute ischaemic stroke with carotid stenosis显示文摘Background There is concern that blood pressure(BP)lowering in acute stroke may compromise cerebral perfusion and worsen outcome in the presence of carotid stenosis.We assessed the effect of glyceryl trinitrate(GTN)in patients with carotid stenosis using data from the Efficacy of Nitric Oxide in Stroke(ENOS)Trial.Methods ENOS randomised 4011 patients with acute stroke and raised systolic BP(140-220 mm Hg)to transdermal GTN or no GTN within 48 hours of onset.Those on prestroke antihypertensives were also randomised to stop or continue their medication for 7 days.The primary outcome was the modified Rankin Scale(mRS)at day 90.Ipsilateral carotid stenosis was split:<30%;30-<50%;50-<70%;≥70%.Data are ORs with 95%CIs adjusted for baseline prognostic factors.results 2023(60.5%)ischaemic stroke participants had carotid imaging.As compared with<30%,≥70%ipsilateral stenosis was associated with an unfavourable shift in mRS(worse outcome)at 90 days(OR 1.88,95%CI 1.44 to 2.44,p<0.001).Those with≥70%stenosis who received GTN versus no GTN had a favourable shift in mRS(OR 0.56,95%CI 0.34 to 0.93,p=0.024).In those with 50-<70%stenosis,continuing versus stopping prestroke antihypertensives was associated with worse disability,mood,quality of life and cognition at 90 days.Clinical outcomes did not differ across bilateral stenosis groups.Conclusions Following ischaemic stroke,severe ipsilateral carotid stenosis is associated with worse functional outcome at 90 days.GTN appears safe in ipsilateral or bilateral carotid stenosis,and might improve outcome in severe ipsilateral carotid stenosis. | Jason P Appleton Lisa J Woodhouse Andrew Belcher Daniel Bereczki Eivind Berge Valeria Caso Hui Meng Chang Hanne K Christensen Ronan Collins John Gommans Ann C Laska George Ntaios Serefnur Ozturk Gillian M Sare Szabolcs Szatmari Yongjun Wang Joanna M Wardlaw Nikola Sprigg Philip M Bath for the ENOS investigators | 2019 | Stroke & Vascular Neurology2019,4,1: | 6 |
| 4 | Increased catabolism and decreased unsaturation of ganglioside in patients with inflammatory bowel disease显示文摘AIM: To investigate whether accelerated catabolism of ganglioside and decreased ganglioside content contribute to the etiology of pro-inflammatory intestinal disease. METHODS: Intestinal mucosa from terminal ileum or colon was obtained from patients with ulcerative colitis or inflammatory Crohn's disease(n = 11) undergoing bowel resection and compared to control samples of normal intestine from patients with benign colon polyps(n = 6) and colorectal cancer(n = 12) in this observational case-control study. Gangliosides and phospholipids of intestinal mucosa were characterized by class and ceramide or fatty acid composition using liquid chromatography triple-quad mass spectrometry. Content and composition of ganglioside classes GM1, GM3, GD3, GD1 a, GT1 and GT3 were compared among subject groups. Content and composition of phospholipid classes phosphatidylcholine(PC) and phosphatidylethanolamine were compared among subject groups. Unsaturation index of individual ganglioside and phospholipid classes was computed and compared among subject groups. Ganglioside catabolism enzymes beta-hexosaminidase A(HEXA) and sialidase-3(NEU3) were measured in intestinal mucosa using western blot and compared among subject groups. RESULTS: Relative GM3 ganglioside content was 2-fold higher(P < 0.05) in intestine from patients with inflammatory bowel disease(IBD) compared to control intestine. The quantity of GM3 and ratio of GM3/GD3 was also higher in IBD intestine than control tissue(P < 0.05). Control intestine exhibited 3-fold higher(P < 0.01) relative GD1 a ganglioside content than IBD intestine. GD3 and GD1 a species of ganglioside containing three unsaturated bonds were present in control intestine, but were not detected in IBD intestine. The relative content of PC containing more than two unsaturated bonds was 30% lower in IBD intestine than control intestine(P < 0.05). The relative content of HEXA in IBD intestine was increased 1.7-fold(P < 0.05) and NEU3 was increased 8.3-fold(P < 0.01) compared to normal intestine. Intestinal mucosa in IBD is characterized by increased GM3 content, decreased GD1 a, and a reduction in polyunsaturated fatty acid constituents in GD3, GD1 a and PC.CONCLUSION: This study suggests a new paradigm by proposing that IBD occurs as a consequence of increased metabolism of specific gangliosides. | John J Miklavcic Glen K Shoemaker Vera C Mazurak M Tom Clandinin Tasha DL Hart Kareena L Schnabl Gordon M Lees Bodil MK Larsen Oliver F Bathe Alan BR Thomson M Tom Clandinin | 2015 | World Journal of Gastroenterology2015,21,35: | 3 |
| 5 | Remote platelet function testing using P-selectin expression in patients with recent cerebral ischaemia on clopidogrel显示文摘Background Antiplatelet agents reduce recurrence after cerebral ischaemia but are not effective in all patients,in part because of treatment resistance.The primary aim was to assess the proportion of patients who are insensitive to clopidogrel.The secondary aim was to assess the association between insensitivity to clopidogrel and recurrent cerebrovascular events.Methods Following written informed consent,independent patients with a recent non-cardioembolic ischaemic stroke or transient ischaemic attack,and taking clopidogrel,were enrolled.Platelet function was assessed with remote measurement of surface expression of P-selectin(CD62P)using commercial kits sensitive to aspirin or clopidogrel.Participants’general practitioners provided details on recurrent vascular events at least 90 days later.Data are mean(SD)and median[IQR].Resistance was defined as:aspirin median fluorescence(MF)>500 units,clopidogrel MF>860 units.Non-parametric descriptors and tests were used.Results 63 patients were recruited:mean age 64(13.7)years,women 47%.At baseline,59(95%)patients were taking clopidogrel alone with 3(5%)on combined clopidogrel and aspirin.Assessment of platelet surface P-selectin revealed:aspirin test 528[317,834],>50054.8%;clopidogrel test 429[303,656],>86011.3%.No participants on aspirin and clopidogrel showed aspirin resistance.Thirteen(20.6%)patients had a recurrent cerebrovascular event;those with an ischaemic stroke had a non-significantly higher baseline P-selectin using the clopidogrel test as compared with those with no recurrence:626[380,801]versus 406[265,609],p=0.08.Conclusions Remote measurement of platelet function assessed using the platelet surface expression of P-selectin is feasible.11%of patients taking clopidogrel showed resistance.No significant associations were noted between clopidogrel resistance and recurrent ischaemic events. | Jason Philip Appleton Carla Richardson Natalia Dovlatova Jane May Nikola Sprigg Stan Heptinstall Philip M Bath | 2021 | Stroke & Vascular Neurology2021,6,1: | 2 |
| 6 | PCR-SSCP comparison of 16S rDNA sequence diversity in soil DNA obtained using different isolation and purification methods 显示文摘 | Stach J E M Bathe S Clapp J P | 2001 | FEMS Microbiology Ecology2001,36,: | 2 |
| 7 | 轻型缺血性卒中或短暂性脑缺血发作的早期双联抗血小板治疗显示文摘王拥军及同事探讨了应用双联抗血小板治疗预防卒中复发或短暂性脑缺血发作的最新证据。轻型缺血性卒中和短暂性脑缺血发作(TIA)患者在头几周内有较高的卒中及其他血管事件的复发风险(5%~11.7%严。双联抗血小板治疗,包括氯吡格雷和阿司匹林,是减少卒中复发的有效治疗策略Magic Group的专家小组(http://gffzz25d7f5dd9bdf4c9ehc0bnbx5bwf5f6vvw.ffgz.tsg.suse.edu.cn/)最近在The BMJ中发表了一个强烈的快速推荐建议,即对于轻型缺血性卒中和TIA患者应在症状出现24小时内开始双联抗血小板治疗,并持续10~21天3。 | 王拥军 S. Claiborne Johnston Philip M Bath James C. Grotta 潘岳松 Pierre Amarenco 王伊龙 Tabassome Simon Jong Sung Kim Jiann-Shing Jeng 刘丽萍 林毅 Ka Sing Lawrence Wong David Wang 李昊 | 2019 | 英国医学杂志中文版2019,22,5: | 2 |
| 8 | Finite element formulation and solution of nonlinear heat transfer显示文摘 | Bathe K J Khoshgoftaar M R | 1979 | Nuclear Engineering and Design1979,51,: | 2 |
| 9 | High blood pressure in acute stroke and subsequent outcome: a systematic review 显示文摘 | Willmot M Leonardi-Bee J Bath PM | 2004 | Hypertension2004,43,1: | 1 |
| 10 | High blood pressure in acute stroke and subsequent outcome: a systematic review显示文摘 | Willmot M Leonardi-Bee J Bath PM | 2004 | Hypertension2004,43,1: | 1 |
| 11 | Finite element free surface seepage analysis without mesh iteration显示文摘 | Bathe K J Khoshgoftaar M R | 1979 | Numerical analytical methods in Geomechanics1979,3,1: | 1 |
| 12 | Serum S - 100 protein,relationship to clinical outcome in acute stroke显示文摘 | Abraha H D Butterworth R J Bath P M | 1997 | Ann Clin Biochem1997,34,4: | 1 |
| 13 | High blood pressure in a-cute stroke and subsequent outcome:a systematic review显示文摘 | Willmot M Leonardi-Bee J Bath PM | 2004 | Hy-pertension2004,43,1: | 1 |
| 14 | Bmi1 transgene induces lymphomas and collaborates with myc in tumorigenesis显示文摘 | Haupt Y Bath M L Harris A W | 1993 | Oncogene1993,8,11: | 1 |
| 15 | Bmi1 transgene induces lymphomas and collaborates with myc in tumorigenesis显示文摘 | Haupt Y Bath M L Harris A W | 1993 | Oncogene1993,8,11: | 1 |
| 16 | The architecture of complex weighted networks显示文摘 | Barrat A Bathélemy M Pastor-Satorras R | 2004 | Proc Natl Acad Sci USA2004,101,11: | 1 |
| 17 | High blood pressure in acute stroke and subsequent outcome: a systematic review 显示文摘 | Willmot M Leonardi-Bee J Bath PM | 2004 | Hypertension2004,43,1: | 1 |
| 18 | Bmi1 transgene induces lymphomas and collaborates with myc in tumorigenesis显示文摘 | Haupt Y Bath M L Harris A W | 1993 | Oncogene1993,8,11: | 1 |
| 19 | Genotyping of environmental and clinical Stenotrophomonas maltophilia:emerging disease patterns and challenges for treatment显示文摘 | Adamek M Overhage J Bathe S | 2011 | Expert Rev Anti Infect Ther2011,9,4: | 1 |
| 20 | Interventions for deliberately alteringblood pressure in acute stroke显示文摘 | Geeganage C M Bath P M | 2009 | Stroke2009,40,8: | 1 |