ORCID Profile
0000-0001-9866-4734
Current Organisation
The University of Edinburgh
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Publisher: Elsevier BV
Date: 2006
Publisher: Elsevier BV
Date: 03-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-09-2003
DOI: 10.1212/01.WNL.0000078033.81925.80
Abstract: The APOE -ε4 allele is associated with risk for Alzheimer’s disease (AD) and poorer outcome after head injury. Several studies show that polymorphisms in the promoter that influence APOE expression also increase risk for AD. The authors’ data from a study of 92 patients are consistent with a possible influence of the G-219T promoter polymorphism on outcome after head injury. The group with unfavorable outcome had a genotype frequency distribution similar to that found in AD.
Publisher: American Medical Association (AMA)
Date: 03-03-2010
Abstract: A low ankle brachial index (ABI) indicates atherosclerosis and an increased risk of cardiovascular and cerebrovascular events. Screening for a low ABI can identify an asymptomatic higher risk group potentially amenable to preventive treatments. To determine the effectiveness of aspirin in preventing events in people with a low ABI identified on screening the general population. The Aspirin for Asymptomatic Atherosclerosis trial was an intention-to-treat double-blind randomized controlled trial conducted from April 1998 to October 2008, involving 28,980 men and women aged 50 to 75 years living in central Scotland, free of clinical cardiovascular disease, recruited from a community health registry, and had an ABI screening test. Of those, 3350 with a low ABI (< or = 0.95) were entered into the trial, which was powered to detect a 25% proportional risk reduction in events. Once daily 100 mg aspirin (enteric coated) or placebo. The primary end point was a composite of initial fatal or nonfatal coronary event or stroke or revascularization. Two secondary end points were (1) all initial vascular events defined as a composite of a primary end point event or angina, intermittent claudication, or transient ischemic attack and (2) all-cause mortality. After a mean (SD) follow-up of 8.2 (1.6) years, 357 participants had a primary end point event (13.5 per 1000 person-years, 95% confidence interval [CI], 12.2-15.0). No statistically significant difference was found between groups (13.7 events per 1000 person-years in the aspirin group vs 13.3 in the placebo group hazard ratio [HR], 1.03 95% CI, 0.84-1.27). A vascular event comprising the secondary end point occurred in 578 participants (22.8 per 1000 person-years 95% CI, 21.0-24.8) and no statistically significant difference between groups (22.8 events per 1000 person-years in the aspirin group vs 22.9 in the placebo group HR, 1.00 95% CI, 0.85-1.17). There was no significant difference in all-cause mortality between groups (176 vs 186 deaths, respectively HR, 0.95 95% CI, 0.77-1.16). An initial event of major hemorrhage requiring admission to hospital occurred in 34 participants (2.5 per 1000 person-years) in the aspirin group and 20 (1.5 per 1000 person-years) in the placebo group (HR, 1.71 95% CI, 0.99-2.97). Among participants without clinical cardiovascular disease, identified with a low ABI based on screening a general population, the administration of aspirin compared with placebo did not result in a significant reduction in vascular events. isrctn.org Identifier: ISRCTN66587262.
Publisher: Wiley
Date: 09-2002
DOI: 10.1046/J.1528-1157.2002.45401.X
Abstract: This randomised, double-blind study compared the newer antiepileptic drugs (AEDs) gabapentin (GBP) and lamotrigine (LTG) as monotherapy in newly diagnosed epilepsy. Patients with partial seizures with and/or without secondary generalization or primary generalized tonic-clonic seizures were randomized to either GBP or LTG. During 2- and 6-week titration periods, respectively, GBP dosage reached 1,800 mg/day, and LTG, 150 mg/day. In the subsequent 24-week maintenance phase, the dose could be adjusted based on seizure control or adverse events between 1,200 and 3,600 mg/day for GBP and 100 and 300 mg/day for LTG. The primary end point was time to exit, a composite of efficacy and tolerability. Evaluable patients were used for the primary efficacy analysis, whereas tolerability was examined on an intent-to-treat basis. A total of 309 patients was randomized, and 291 (148 GBP, 143 LTG) were included in the evaluable population. Nineteen patients in each group had an exit event. The median time to exit was 69 days for GBP and 48 days for LTG. The hazard ratio was estimated as 1.043 (90% confidence intervals, 0.602-1.809). Overall, 106 (71.6% of the evaluable population) GBP-treated and 96 (67.1%) LTG-treated patients completed the study. Of those, 80 (75.5%) patients taking GBP and 73 (76.0%) taking LTG remained seizure free during the final 12 weeks of treatment. Only 14 (8.9%) GBP-treated patients and 15 (9.9%) LTG-treated patients withdrew because of study drug-related adverse events. GBP and LTG monotherapy were similarly effective and well tolerated in patients with newly diagnosed epilepsy.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2009
Publisher: Springer Science and Business Media LLC
Date: 23-01-2011
DOI: 10.1007/S10519-011-9449-2
Abstract: There is increasing evidence to suggest that elevated plasma levels of fibrinogen are associated with late-life cognitive performance. This study tested the association of single nucleotide polymorphisms in the fibrinogen α (FGA) and β (FGB) genes with cognitive performance. Data were analysed from three community-dwelling populations of older persons (>50 years) in central Scotland: the Aspirin for Asymptomatic Atherosclerosis (AAA) Trial (n = 2,091), the Edinburgh Type 2 Diabetes Study (ET2DS, n = 1,066), and the Lothian Birth Cohort 1936 (LBC1936, n = 1,091). Cognition was assessed using a battery of five, seven, and four psychometric tests, respectively. This information was used to derive a general cognitive factor. Weakly significant associations were found between the rs4220 (FGB), and rs2227412 (FGB) SNPs and a single test of cognitive performance in the AAA Trial (p < 0.05). These findings did not replicate in the LBC1936 or ET2DS cohorts, except for the rs2227412 SNP, which was significantly associated with the general cognitive factor in the ET2DS (p = 3.3 × 10(-4)). A summary term that combined results from all three studies suggested that the rs2227412 genotype associated with reduced cognitive ability also associated with higher plasma fibrinogen levels. These findings suggest a tentative role for fibrinogen as a determinant of late-life cognitive performance and justify further attempts at replication in older persons.
Publisher: Elsevier BV
Date: 11-2011
DOI: 10.1111/J.1538-7836.2011.04486.X
Abstract: Deep vein thrombosis (DVT) is an important complication of stroke, but the evidence to support commonly used prophylactic strategies is conflicting. To describe the incidence, extent, associated clinical features and evolution of DVT after stroke. The CLOTS trials 1 and 2 together randomized 5632 immobile stroke patients in 135 hospitals in nine countries. We screened patients for asymptomatic DVT with compression duplex ultrasound (CDU) at about 7-10 days and again at about 25-30 days after enrollment. Six hundred and forty-one (11.4%) of 5632 patients had DVT detected on the first CDU scan at a median of 8 days (interquartile range [IQR] 7-10 days) after enrollment, and an additional 176 (3.1%) had a DVT on the second CDU scan at a median of 28 days (IQR 26-30 days). Of the 817 with DVTs, 289 (35%) were symptomatic and 39 (5%) had pulmonary embolism (PE) confirmed by imaging. Six hundred and seventy-six (83%) were unilateral, 141 (17%) were bilateral, 322 (39%) were limited to calf veins, 172 (21%) were popliteal, and 323 (40%) were femoral. Among the 542 patients with DVT and a weak leg, the DVT affected the weaker leg in 396 (73%), the stronger leg in 59 (11%), and was bilateral in 87 (16%). Among the 318 patients with a DVT detected on the first CDU scan who had a second scan, the DVT regressed in 148 (47%), stayed the same in 140 (44%), and progressed in only 30 (9%). Although most DVTs develop within the first week, some develop later, and some early DVTs progress. Any prophylaxis needs to be started early but ideally continued for at least 4 weeks.
Publisher: Oxford University Press (OUP)
Date: 02-08-2010
Abstract: Patients with medically unexplained symptoms (MUS) are commonly referred to specialist clinics. Repeated referrals suggest unmet patient need and inefficient use of resources. How often does this happen, who are the patients and how are they referred? The design of the study is a case-control survey. The setting of the study is five general practices in Scotland, UK. The cases were 193 adults with three or more referrals over 5 years, at least two of which resulted in a diagnosis of MUS. The controls were (i) patients referred only once over 5 years and (ii) patients with three or more referrals with symptoms always diagnosed as medically explained. The measures of the study are SF-12 physical and mental component summaries symptom count and number of referrals, number of different GPs who had referred and number of specialist follow-up appointments. A total of 1.1% [95% confidence interval (CI) 1.0-1.2%] of patients had repeated (median 3, range 2-6) referrals with MUS. Compared to infrequently referred controls, they were older and more likely to be female, living alone and unemployed. Compared to controls with medically explained symptoms, their health status was comparable or worse: odds ratio for SF-12 physical component summary<40, 1.2 (95% CI 0.72-2.0) SF-12 mental component summary<40, 1.8 (95% CI 1.1-3.0) reporting eight or more physical symptoms, 2.2 (95% CI 1.2-3.8). They were referred by more GPs and received less specialist follow-up. A small proportion of primary care patients are repeatedly referred to specialist clinics where they receive multiple diagnoses of MUS. The needs of these patients and how they are managed merits greater attention.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2012
Publisher: Elsevier BV
Date: 02-2005
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-07-2014
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.NEULET.2009.04.050
Abstract: We report on the association of KIBRA with memory in two s les of older in iduals assessed on either memory for semantically unrelated word stimuli (Rey Auditory Verbal Learning Test, n=2091), or a measure of semantically related material (the WAIS Logical Memory Test of prose-passage recall, n=542). SNP rs17070145 was associated with delayed recall of semantically unrelated items, but not with immediate recall for these stimuli, nor with either immediate or delayed recall for semantically related material. The pattern of results suggests a role for the T-->C substitution in intron 9 of KIBRA in a component of episodic memory involved in long-term storage but independent of processes shared with immediate recall such as rehearsal involved in acquisition and rehearsal or processes.
Publisher: Elsevier BV
Date: 06-2012
Publisher: Oxford University Press (OUP)
Date: 02-03-2010
Abstract: the association between the rheological factors haematocrit and plasma viscosity and cognitive ability has not been extensively studied. It is possible that blood viscosity affects cerebral blood flow and cognitive function. This study tested the contemporaneous associations between these two markers of rheology and cognitive ability and estimated lifetime cognitive change in an elderly population with type 2 diabetes. a cross-sectional cohort of 1,066 men and women with type 2 diabetes (Edinburgh Type 2 Diabetes Study) was used for the analysis. Plasma viscosity and haematocrit were measured in venous blood s les at baseline. Contemporaneously, a battery of seven cognitive tests was administered to all participants. These data were used to derive a general intelligence factor, g. A vocabulary-based test was also administered as an estimate of prior intelligence, and adjustment for scores on this test was used to estimate lifetime cognitive decline. increased plasma viscosity was associated with poorer age- and sex-adjusted scores on the cognitive domains of processing speed, mental flexibility and general intelligence, g, with standardised regression coefficients -0.092 (P < 0.01), -0.077 (P < 0.05) and -0.093 (P < 0.01), respectively. After adjusting for vocabulary, education level, cardiovascular dysfunction, duration of diabetes and glycaemic control, the associations remained significant for the measure of processing speed and g, with standardised regression coefficients -0.059 (P < 0.05) and -0.051 (P < 0.05). Increased haematocrit was significantly associated with better age- and sex-adjusted cognitive scores on the majority of the tests and with g. However, significant associations were not retained after adjustments for additional covariates. increased plasma viscosity is associated with decreased cognitive ability and increased estimated lifetime cognitive decline. The relationship between haematocrit and cognitive ability requires further study.
Publisher: BMJ
Date: 09-2008
DOI: 10.1136/BMJ.A1198
Publisher: Springer Science and Business Media LLC
Date: 10-10-2009
DOI: 10.1007/S10519-009-9302-Z
Abstract: It is unknown whether the relationship between raised inflammatory biomarker levels and late-life cognitive ability is causal. We explored this issue by testing the association between genetic regulators of plasma C-reactive protein (CRP) and cognition. Data were analysed from four cohorts based in central Scotland (Total N = 4,782). Associations were tested between variants in the CRP gene and both plasma CRP levels and a battery of neuropsychological tests, including a vocabulary-based estimate of peak prior cognitive ability and a general (summary) cognitive factor score, or 'g'. CRP levels were associated with a number of variants in the CRP gene (SNPs), including rs1205, rs1130864, rs1800947, and rs1417938 (P range 4.2e-06 to 0.041). Higher CRP levels were also associated with vocabulary-adjusted cognitive ability, used here to estimate lifetime cognitive change (P range 1.7e-04 to 0.038). After correction for multiple testing and adjustment for age and sex, no statistically significant associations were found between the SNPs and cognition. CRP is unlikely to be a causal determinant of late-life cognitive ability.
Publisher: Springer Science and Business Media LLC
Date: 22-06-2010
DOI: 10.1007/S10519-010-9372-Y
Abstract: The dopaminergic neurotransmitter system of the brain is involved in working memory and other cognitive functions. Studies suggest an important role for dopamine synthesis and uptake in modulation of human cognitive processes. We studied the association between polymorphisms in the catechol-o-methyl transferase (COMT) and dopamine receptor D2 (DRD2) genes and general cognitive ability in a secondary analysis of 2091 men and women, aged 55-80 years living in Scotland. General cognitive ability 'g' was derived from five cognitive tests of different domains. COMT was not associated with cognitive ability in this population. The DRD2 C:C genotype of rs6277 was associated with decreased general cognitive ability 'g' (p = 0.003), and DRD2 rs1800497 heterozygotes had lowest mean general cognitive ability 'g' (p = 0.007). There was an indication of a potential interaction between the DRD2 SNPs.
Publisher: SAGE Publications
Date: 09-03-2012
Publisher: Elsevier BV
Date: 12-2008
Publisher: American Diabetes Association
Date: 03-12-2009
DOI: 10.2337/DB09-1163
Abstract: To determine whether circulating levels of the inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-α are associated with cognitive ability and estimated lifetime cognitive decline in an elderly population with type 2 diabetes. A cross-sectional study of 1,066 men and women aged 60–75 years with type 2 diabetes and living in Lothian, Scotland (the Edinburgh Type 2 Diabetes Study), was performed. Seven cognitive tests were used to measure abilities in memory, nonverbal reasoning, information processing speed, executive function, and mental flexibility. The results were used to derive a general intelligence factor (g). A vocabulary–based test was administered as an estimate of peak prior cognitive ability. Results on the cognitive tests were assessed for statistical association with inflammatory markers measured in a venous blood s le at the time of cognitive testing. Higher IL-6 and TNF-α levels were associated with poorer age- and sex-adjusted scores on the majority of the in idual cognitive tests. They were also associated with g using standardized regression coefficients −0.074 to −0.173 (P & 0.05). After adjusting for vocabulary, education level, cardiovascular dysfunction, duration of diabetes, and glycemic control, IL-6 remained associated with three of the cognitive tests and with g. In this representative population of people with type 2 diabetes, elevated circulating levels of inflammatory markers were associated with poorer cognitive ability. IL-6 levels were also associated with estimated lifetime cognitive decline.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2014
DOI: 10.1161/STROKEAHA.113.004362
Abstract: Intravenous recombinant tissue-type plasminogen activator (r-tPA), despite a risk of early symptomatic intracranial hemorrhage (sICH), is of net clinical benefit to acute stroke patients. We tested if predictive models could identify patients least likely to be harmed by sICH or those who gained no net benefit. We used the Third International Stroke Trial (IST-3) trial data set, an international, multicenter, open treatment randomized trial of 0.9 mg/kg r-tPA versus control in 3035 patients with acute ischemic stroke. We compared the discrimination and calibration of previously developed predictive models for ICH and poststroke poor outcome and developed a new model using variables selected by systematic review. We calculated the absolute and relative risk reduction of death or dependency with r-tPA in patients at a low, medium, or high predicted risk of sICH or poor functional outcome. Prediction models for sICH or poor outcome (Hemorrhage After Thrombolysis [HAT] Sugar, Early Infarct Signs, Dense Artery, Age, National Institutes of Health (NIH) Stroke Score (SEDAN) Glucose Race Age Sex Pressure Stroke Severity [GRASPS] Stroke Thrombolytic Predictive Instrument Dense Artery, Rankin Score, Age, Glucose, Onset to Treatment Time, NIHSS [DRAGON] Totaled Health Risks in Vascular Events [THRIVE] our new model and a model with National Institutes of Health Stroke Scale and age) had similar area under receiver operator characteristic curves (AUROCC) to predict sICH ( P for difference .05). The simplest model (with covariates National Institutes of Health Stroke Scale and age) predicted both sICH (AUROCC, 0.63 95% CI, 0.58–0.68) and poststroke poor functional outcome (AUROCC, 0.80 95% CI, 0.77–0.82) similarly to complex models. There was no evidence that the effect of r-tPA in patients at high predicted risk of sICH or poor functional outcome after stroke was less than in those at lower risk. There is a clinically relevant net positive effect of r-tPA in patients with acute stroke at a high predicted risk of sICH or poor functional outcome. URL: www.controlled-trials.com . Unique identifier: ISRCTN25765518.
Publisher: Springer Science and Business Media LLC
Date: 02-2014
Publisher: Wiley
Date: 04-2010
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Gordon Murray.