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Search Results: 1 - 10 of 401665 matches for " Gillian M. Sare "
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A Randomised Controlled Trial of Triple Antiplatelet Therapy (Aspirin, Clopidogrel and Dipyridamole) in the Secondary Prevention of Stroke: Safety, Tolerability and Feasibility
Nikola Sprigg, Laura J. Gray, Tim England, Mark R. Willmot, Lian Zhao, Gillian M. Sare, Philip M. W. Bath
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0002852
Abstract: Background Aspirin, dipyridamole and clopidogrel are effective in secondary vascular prevention. Combination therapy with three antiplatelet agents might maximise the benefit of antiplatelet treatment in the secondary prevention of ischaemic stroke. Methodology/Principal Findings A randomised, parallel group, observer-blinded phase II trial compared the combination of aspirin, clopidogrel and dipyridamole with aspirin alone. Adult patients with ischaemic stroke or transient ischaemic attack (TIA) within 5 years were included. The primary outcome was tolerability to treatment assessed as the number of patients completing randomised treatment. Recruitment was halted prematurely after publication of the ESPRIT trial (which confirmed that combined aspirin and dipyridamole is more effective than aspirin alone). 17 patients were enrolled: male 12 (71%), mean age 62 (SD 13) years, lacunar stroke syndrome 12 (71%), median stroke/TIA onset to randomisation 8 months. Treatment was discontinued in 4 of 9 (44%) patients receiving triple therapy vs. none of 8 taking aspirin (p = 0.08). One recurrent stroke occurred in a patient in the triple group who was noncompliant of all antiplatelet medications. The number of patients with adverse events and bleeding complications, and their severity, were significantly greater in the triple therapy group (p<0.01). Conclusions/Significance Long term triple antiplatelet therapy was asociated with a significant increase in adverse events and bleeding rates, and their severity, and a trend to increased discontinuations. However, the patients had a low risk of recurrence and future trials should focus on short term therapy in high risk patients characterised by a very recent event or failure of dual antiplatelet therapy. Trial Registration Controlled-Trials.com ISRCTN83673558
Effect of Telmisartan on Cerebral and Systemic Haemodynamics in Patients with Recent Ischaemic Stroke: A Randomised Controlled Trial
Gillian M. Sare,Andrew Ghadami,Sandeep Ankolekar,Timothy England,Fiona Hammonds,Margaret Adrian,Judith Clarke,Lynn Stokes,Dorothee Auer,Philip M. W. Bath
ISRN Stroke , 2013, DOI: 10.1155/2013/587954
Abstract: High blood pressure (BP) is common in acute stroke and is independently associated with a poor outcome. Lowering BP might improve outcome if cerebral blood flow (CBF) is unaffected in the presence of dysfunctional autoregulation. We investigated the effect of telmisartan on systemic and cerebral haemodynamics in patients with recent stroke. Patients with ischaemic stroke (<5 days) were randomised to 90 days of telmisartan (80?mg) or placebo. CBF (primary outcome) was measured using xenon CT at baseline and 4 hours. BP and transcranial doppler (TCD) were performed at baseline, 4 hours after-treatment, and on days 4, 7, and 90. Cerebral perfusion pressure and zero filling pressure (ZFP) were calculated. Of a planned 24 patients, 17 were recruited. Telmisartan significantly accentuated the fall in systolic and diastolic BP over 90 days (treatment-time interaction , resp.) but did not alter BP at 4 hours after treatment (171/99 versus 167/87?mmHg), CBF, or CBF velocity. ZFP was significantly lower in the treatment group . Impairment at 7 days and dependency at 90 days did not differ between the groups. In this underpowered study, telmisartan did not significantly alter BP or CBF after the first dose. Telmisartan reduced BP over the subsequent 90 days and significantly lowered ZFP. This trial is registered with ISRCTN 41456162. 1. Introduction High blood pressure (BP) is common and associated independently with a poor outcome in patients with acute stroke [1–3]. However, there are no definitive data guiding the management of high BP. Individual small studies of BP modifying agents in acute stroke have indicated potential efficacy [4–6] or harm [7, 8]. A metaregression analysis of these and other trials suggested that systolic BP reductions in the order of 10–15?mmHg reduction were associated with a trend to reduced death at the end of trial, although the confidence intervals were wide and compatible with benefit or harm [9]; more extreme BP lowering or any form of BP elevation was associated with harm [3, 9]. The recently published large SCAST trial showed that candesartan only modestly lowered BP and had no beneficial effect on dependency or further vascular events [10]. Further large trials of BP lowering in acute stroke are underway including ENOS and INTERACT-2 [11]. However, since antihypertensive agents vary in their mode of action and their potential effects on cerebral blood flow, trials of individual agents may not be generalisable across all antihypertensive agents. Cerebral autoregulation is dysfunctional in acute stroke [12] and BP lowering could
Determining the Feasibility of Ambulance-Based Randomised Controlled Trials in Patients with Ultra-Acute Stroke: Study Protocol for the “Rapid Intervention with GTN in Hypertensive Stroke Trial” (RIGHT, ISRCTN66434824)
Sandeep Ankolekar,Gillian Sare,Chamila Geeganage,Michael Fuller,Lynn Stokes,Nikola Sprigg,Ruth Parry,A. Niroshan Siriwardena,Philip M. W. Bath
Stroke Research and Treatment , 2012, DOI: 10.1155/2012/385753
Abstract: Background. Time from acute stroke to enrolment in clinical trials needs to be reduced to improve the chances of finding effective treatments. No completed randomised controlled trials of ambulance-based treatment for acute stroke have been reported in the UK, and the practicalities of recruiting, consenting, and treating patients are unknown. Methods. RIGHT is an ambulance based, single-blind, randomised controlled trial with blinded-outcome assessment. The trial will assess feasibility of using ambulance services to deliver ultra-acute stroke treatments; a secondary aim is to assess the effect of glyceryl trinitrate (GTN) on haemodynamic variables and functional outcomes. Initial consent, randomisation, and treatment are performed by paramedics prior to hospitalisation. Patients with ultra-acute stroke (≤4 hours of onset) are randomised to transdermal GTN (5?mg/24 hours) or gauze dressing daily for 7 days. The primary outcome is systolic blood pressure at 2 hours. Secondary outcomes include feasibility, haemodynamics, dependency, and other functional outcomes. A nested qualitative study is included. Trial Status. The trial has all relevant ethics and regulatory approvals and recruitment started on February 15, 2010. The trial stopped recruitment in December 2011 after 41 patients were recruited. Trial Registration. The trial registration number is ISRCTN66434824 and EudraCT number is 2007-004766-40. 1. Background Finding acute interventions which reduce early brain damage and improve outcome after acute stroke is of major importance and has proved challenging. Irreversible brain damage starts in the first minutes to hours after a stroke [1] and acute stroke treatments can be highly time dependent; outcomes after stroke thrombolysis are better when treatment is given early [2]. Ambulance administration of emergency treatment is standard in acute medical emergencies such as acute myocardial infarction and asthma; thrombolysis for MI was given 45 minutes earlier if administered in an ambulance than at hospital [3]. Treatments for acute ischaemic stroke (AIS) are not routinely administered prior to hospital since current therapies reduce haemostasis (e.g., aspirin and alteplase) and need neuroimaging to exclude primary intracerebral haemorrhage (PICH). However, other potential treatments for acute stroke such as neuroprotection and management of physiological disturbances (e.g., high blood pressure [BP], hyperglycaemia and pyrexia) do not necessarily need prior neuroimaging and could be delivered before hospitalisation. As benefits of such interventions
Open questions: missing pieces from the immunological jigsaw puzzle
Griffiths Gillian M
BMC Biology , 2013, DOI: 10.1186/1741-7007-11-10
Global Diversity and Review of Siphonophorae (Cnidaria: Hydrozoa)
Gillian M. Mapstone
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0087737
Abstract: In this review the history of discovery of siphonophores, from the first formal description by Carl Linnaeus in 1785 to the present, is summarized, and species richness together with a summary of world-wide distribution of this pelagic group within the clade Hydrozoa discussed. Siphonophores exhibit three basic body plans which are briefly explained and figured, whilst other atypical body plans are also noted. Currently, 175 valid siphonophore species are recognized in the latest WoRMS world list, including 16 families and 65 genera. Much new information since the last review in 1987 is revealed from the first molecular analysis of the group, enabling identification of some new morphological characters diagnostic for physonect siphonophores. Ten types of nematocysts (stinging cells) are identified in siphonophores, more than in any other cnidarian; these are incorporated into batteries in the side branches of the tentacles in most species (here termed tentilla), and tentilla are reviewed in the last section of this paper. Their discharge mechanisms are explained and also how the tentilla of several physonect siphonophores are modified into lures. Of particular interest is the recent discovery of a previously unknown red fluorescent lure in the tentilla of the deep sea physonect Erenna, the first described example of emission of red light by an invertebrate to attract prey.
Land of a Couple of Dances: Global and Local Influences on Freestyle Play in Dance Dance Revolution
Fibreculture Journal , 2006,
Abstract: This paper traces successful and unsuccessful attempts to shape the meanings of the video game Dance Dance Revolution, specifically with reference to what "dancing" means in this context, as the game moves between various interested parties - game developers, players, Internet forum participants, and other media producers. Drawing on Actor-Network Theory and the network analyses of Manuel Castells, the paper reconstructs the forces shaping players' stylistic decisions through an analysis of dance game machines and software, and of a single forum thread on DDRFreak.com, a major website in the dance game community. The paper asks who decides how DDR players dance and at what times? Are the decisions about play made in the development meeting, the arcade, competitions, online or around the home console? Globally, how do some regions or groups emerge as experts or leaders in play style? Analysis indicates that within the United States, Californian players from major cities dominate discussion, supported by the global flows of people, resources, and capital through the state. The dominant players support their stated norms for play through recourse to mainstream conceptions of masculinity, rap music and associated styles of dance.
Lifestyle in adults aged 35 years who were born with open spina bifida: prospective cohort study
Gillian M Hunt, Pippa Oakeshott
Fluids and Barriers of the CNS , 2004, DOI: 10.1186/1743-8454-1-4
Abstract: Ascertainment was 100%. There had been 63 deaths, mainly of the most severely affected. The mean age of the 54 survivors was 35 years. The outcome in terms of disability ranged from apparent normality to total dependency. It reflected both the neurological deficit, which had been recorded in infancy in terms of sensory level, and events in the CSF shunt history. Overall about 2 in 5 of the survivors lived independently in the community, 2 in 5 drove a car, 1 in 5 was in competitive employment and 1 in 5 could walk 50 metres.Although those who survived to age 35 years tended to be less disabled, 2 in 5 continued to need daily care.Neurosurgical intervention in babies with open spina bifida had dramatic results in terms of survival. However, the disability and the complications of the survivors were often severe [1-5]. Many efforts were made to enable them to walk, to control their urinary incontinence while safeguarding renal function, and to overcome problems associated with the shunt treatment of hydrocephalus. Promising new methods of management, such as the psoas transplant, urinary diversion and artificial urinary sphincters, which seemed highly successful in the short term, lost favour after 10 or 15 years because of disappointing long-term results. In this unsteady course of progress it is helpful to have a long term follow up of a complete cohort of patients with open spina bifida as a realistic basis for helping parents facing the difficult decisions about termination of an affected pregnancy or treatment after birth.In 1963 the Regional Neurosurgical Unit at Addenbrooke's Hospital, Cambridge, England offered treatment to all cases of open spina bifida, without any attempt at selection. Between 1963 and 1971, after a detailed neurological examination, 117 babies (50 male, 67 female) had their open spinal defects closed within 48 hours of birth. A ventriculo-atrial cerebrospinal fluid (CSF) shunt was inserted for hydrocephalus when required.In 2002 all surviv
Lost in the Forest, Stuck in the Trees: Dispositional Global/Local Bias Is Resistant to Exposure to High and Low Spatial Frequencies
Gillian Dale, Karen M. Arnell
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0098625
Abstract: Visual stimuli can be perceived at a broad, “global” level, or at a more focused, “local” level. While research has shown that many individuals demonstrate a preference for global information, there are large individual differences in the degree of global/local bias, such that some individuals show a large global bias, some show a large local bias, and others show no bias. The main purpose of the current study was to examine whether these dispositional differences in global/local bias could be altered through various manipulations of high/low spatial frequency. Through 5 experiments, we examined various measures of dispositional global/local bias and whether performance on these measures could be altered by manipulating previous exposure to high or low spatial frequency information (with high/low spatial frequency faces, gratings, and Navon letters). Ultimately, there was little evidence of change from pre-to-post manipulation on the dispositional measures, and dispositional global/local bias was highly reliable pre- to post-manipulation. The results provide evidence that individual differences in global/local bias or preference are relatively resistant to exposure to spatial frequency information, and suggest that the processing mechanisms underlying high/low spatial frequency use and global/local bias may be more independent than previously thought.
Mechanisms of HIV Transcriptional Regulation and Their Contribution to Latency
Gillian M. Schiralli Lester,Andrew J. Henderson
Molecular Biology International , 2012, DOI: 10.1155/2012/614120
Abstract: Long-lived latent HIV-infected cells lead to the rebound of virus replication following antiretroviral treatment interruption and present a major barrier to eliminating HIV infection. These latent reservoirs, which include quiescent memory T cells and tissue-resident macrophages, represent a subset of cells with decreased or inactive proviral transcription. HIV proviral transcription is regulated at multiple levels including transcription initiation, polymerase recruitment, transcription elongation, and chromatin organization. How these biochemical processes are coordinated and their potential role in repressing HIV transcription along with establishing and maintaining latency are reviewed. 1. Introduction A critical step in the HIV life cycle is transcriptional regulation of the integrated provirus. Robust transcription assures that sufficient mRNA and genomic RNA are produced for efficient virus assembly and infectivity. Repression of HIV transcription leads to the establishment of HIV latency, which creates repositories for infectious and drug-resistant viruses that reemerge upon treatment failure or interruption [1–4]. The existence of long-lived stable HIV reservoirs was demonstrated by the rebound of virus replication following highly active antiretroviral therapy (HAART) interruption [5–8]. These latent reservoirs, which include quiescent memory T cells, tissue-resident macrophages [9, 10], and potentially hematopoietic stem cells [11], although this is still controversial [12], represent long-lived subsets of cells with decreased or inactive proviral transcription. In general, studies with chronically and acutely infected cells show that mutations in Tat [13, 14], absence of cellular transcription factors [15–18], miRNA machinery [19, 20], and proviral integration into transcriptionally silent sites contribute to postintegration latency [21, 22]. Although there may not be a common mechanism that promotes HIV latency, it is critical to understand the molecular events that establish and maintain latency if strategies to reduce or purge HIV from latent reservoirs are to be devised [9, 23, 24]. HIV transcription is regulated at multiple levels including transcription initiation, polymerase recruitment, transcriptional elongation, and chromatin organization. How these events are coordinated and their role in HIV latency will be reviewed. In particular, mechanisms that contribute to repressing HIV transcription will be highlighted. 2. LTR and Transcription Factors Although viral accessory proteins, such as Vpr, and putative elements within the HIV
TRY-5 Is a Sperm-Activating Protease in Caenorhabditis elegans Seminal Fluid
Joseph R. Smith,Gillian M. Stanfield
PLOS Genetics , 2011, DOI: 10.1371/journal.pgen.1002375
Abstract: Seminal fluid proteins have been shown to play important roles in male reproductive success, but the mechanisms for this regulation remain largely unknown. In Caenorhabditis elegans, sperm differentiate from immature spermatids into mature, motile spermatozoa during a process termed sperm activation. For C. elegans males, sperm activation occurs during insemination of the hermaphrodite and is thought to be mediated by seminal fluid, but the molecular nature of this activity has not been previously identified. Here we show that TRY-5 is a seminal fluid protease that is required in C. elegans for male-mediated sperm activation. We observed that TRY-5::GFP is expressed in the male somatic gonad and is transferred along with sperm to hermaphrodites during mating. In the absence of TRY-5, male seminal fluid loses its potency to transactivate hermaphrodite sperm. However, TRY-5 is not required for either hermaphrodite or male fertility, suggesting that hermaphrodite sperm are normally activated by a distinct hermaphrodite-specific activator to which male sperm are also competent to respond. Within males, TRY-5::GFP localization within the seminal vesicle is antagonized by the protease inhibitor SWM-1. Together, these data suggest that TRY-5 functions as an extracellular activator of C. elegans sperm. The presence of TRY-5 within the seminal fluid couples the timing of sperm activation to that of transfer of sperm into the hermaphrodite uterus, where motility must be rapidly acquired. Our results provide insight into how C. elegans has adopted sex-specific regulation of sperm motility to accommodate its male-hermaphrodite mode of reproduction.
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