Anila Syed - Academia.edu (original) (raw)

Papers by Anila Syed

Research paper thumbnail of The incidence of corpora amylacea (CA) in the optic nerve of patients with Alzheimer's disease

Corpora amylacea (CA) are spherical or ovoid bodies 50-50 microns in diameter. They have been des... more Corpora amylacea (CA) are spherical or ovoid bodies 50-50 microns in diameter. They have been described in normal elderly brain as well as in a number of neurodegenerative disorders. In this study, the incidence of CA in the optic nerves of Alzheimer's disease (AD) patients was compared with normal elderly controls. Samples of optic nerves (MRC Brain Bank, Institute of Psychiatry) were taken from 12 AD patients (age range 69-94 years) and 18 controls (43-82 years). Optic nerves were fixed in 2% buffered glutaraldehyde, post-fixed in osmium tetroxide, embedded in epoxy resin and then sectioned to a thickness of 2 microns. Sections were stained with toluidine blue. CA were present in all of the optic nerves examined. In addition, a number of similarly stained but more irregularly shaped bodies were present. Fewer CA were found in the optic nerves of AD patients compared with controls. By contrast, the number or irregularly shaped bodies was increased in AD. In AD, there may be a p...

Research paper thumbnail of Quantification of axonal loss in Alzheimer’s disease: an image analysis study

The density of axons in the optic nerve, olfactory tract and corpus callosum was quantified in no... more The density of axons in the optic nerve, olfactory tract and corpus callosum was quantified in non-demented elderly subjects and in Alzheimer’s disease (AD) using an image analysis system. In each fibre tract, there was significant reduction in the density of axons in AD compared with non-demented subjects, the greatest reductions being observed in the olfactory tract and corpus callosum. Axonal loss in the optic nerve and olfactory tract was mainly of axons with smaller myelinated cross-sectional areas. In the corpus callosum, a reduction in the number of ‘thin’ and ‘thick’ fibres was observed in AD, but there was a proportionally greater loss of the ‘thick’ fibres. The data suggest significant degeneration of white matter fibre tracts in AD involving the smaller axons in the two sensory nerves and both large and small axons in the corpus callosum. Loss of axons in AD could reflect an associated white matter disorder and/or be secondary to neuronal degeneration.

Research paper thumbnail of A quantitative analysis of optic nerve axons in elderly control subjects and patients with Alzheimer's disease

Folia neuropathologica / Association of Polish Neuropathologists and Medical Research Centre, Polish Academy of Sciences, 2005

To study the density and cross-sectional area of axons in the optic nerve in elderly control subj... more To study the density and cross-sectional area of axons in the optic nerve in elderly control subjects and in cases of Alzheimer's disease (AD) using an image analysis system. Sections of optic nerves from control and AD patients were stained with toluidine blue to reveal axon profiles. The density of axons was reduced in both the center and peripheral portions of the optic nerve in AD compared with control patients. Analysis of axons with different cross-sectional areas suggested a specific loss of the smaller sized axons in AD, i.e., those with areas less that 1.99 microm2. An analysis of axons >11 microm2 in cross-sectional area suggested no specific loss of the larger axons in this group of patients. The data suggest that image analysis provides an accurate and reproducible method of quantifying axons in the optic nerve. In addition, the data suggest that axons are lost throughout the optic nerve with a specific loss of the smaller-sized axons. Loss of the smaller axons ma...

Research paper thumbnail of Lack of reproducibility of assessment of aspirin responsiveness by optical aggregometry and two platelet function tests

Platelets, 2008

The term aspirin-resistance describes the failure of aspirin to inhibit thromboxane A(2) producti... more The term aspirin-resistance describes the failure of aspirin to inhibit thromboxane A(2) production. Many new tests have become available for potentially measuring aspirin responses but some are non-specific and do not isolate COX-1 activity. We previously demonstrated that agreement between two tests (PFA-100 and VerifyNow-ASA) and light transmission aggregation (LTA) was no greater than would be expected by chance. In this study we re-tested the same patients using identical methods after 1 year to determine whether poor agreement might have been due to assessment in the acute phase and whether the results of the individual tests are consistent over time. Platelet function by all three tests was re-tested in the 72 patients who were alive and still receiving low dose ASA therapy one year after the first tests were performed. On re-testing the prevalence of ASA non-responsiveness compared with baseline was 10% vs 17% by the VerifyNow-ASA test, 25% vs 22% by the PFA-100(R), and 1% vs 5% by LTA. Agreement between the tests at 1 year remained poor (kappas: 0.02-0.17) and only one patient was identified as a non-responder by all three tests, in keeping with the theoretical differences between the tests. Within test comparisons of baseline vs 1 year showed moderate agreement for the PFA-100(R) (kappa = 0.44, 95% CI 0.19-0.68, p = 0.0006), a fair agreement for VerifyNow-ASA (kappa = 0.34, 0.04-0.64, p = 0.12) and poor agreement for LTA (kappa = 0.14, -0.11 -0.39, p = 0.24 for ADP; kappa = 0.09, -0.21-0.39, p = 0.41 for arachidonic acid). Agreement between the three tests in identifying aspirin non-responsiveness remained poor in patients who had been taking aspirin for at least 1 year follow-up. Reproducibility over time was no greater than chance for LTA and only moderate for VerifyNow-ASA and PFA-100(R). Lack of consistency over time in identification of apparently non-responsiveness individuals is likely to substantially undermine any ability of these tests to predict risk of recurrent vascular events.

Research paper thumbnail of Density and cross-sectional areas of axons in the olfactory tract in control subjects and Alzheimer’s disease: an image analysis study

Neurological Sciences, 2008

Using an image analysis system to determine whether there is loss of axons in the olfactory tract... more Using an image analysis system to determine whether there is loss of axons in the olfactory tract (OT) in Alzheimer's disease (AD). A retrospective neuropathological study. Nine control patients and eight clinically and pathologically verified AD cases. There was a reduction in axon density in AD compared with control subjects in the central and peripheral regions of the tract. Axonal loss was mainly of axons with smaller (<2.99 microm(2)) myelinated cross-sectional areas. The data suggest significant degeneration of axons within the OT involving the smaller sized axons. Loss of axons in the OT is likely to be secondary to pathological changes originating within the parahippocampal gyrus rather than to a pathogen spreading into the brain via the olfactory pathways.

Research paper thumbnail of Mitochondrial DNA haplogroups and risk of transient ischaemic attack and ischaemic stroke: a genetic association study

The Lancet Neurology, 2010

Background Genetic factors have a role in the pathogenesis of ischaemic stroke, but the main gene... more Background Genetic factors have a role in the pathogenesis of ischaemic stroke, but the main genes involved have yet to be defi ned. Mitochondrial mechanisms have been implicated in the pathophysiology of acute stroke, but the role of mitochondrial DNA (mtDNA) has not been comprehensively studied. We investigated whether there is an association between mtDNA haplotypes and incidence of stroke. Methods The major European mtDNA haplogroups were identifi ed in two independent subpopulations (n=950) from a study of occurrence of transient ischaemic attack (TIA) and ischaemic stroke and were compared with those of patients with acute coronary syndromes from the same populations (n=340) and with those of independent population controls (n=2939). Findings The presence of mtDNA sub-haplogroup K was signifi cantly less frequent in patients with TIA or stroke than in controls in both subpopulations separately and in a pooled analysis (odds ratio 0•54, 95% CI 0•39-0•75, p<0•00001). This association remained highly signifi cant after adjustment for multiple haplogroup comparisons. The association was signifi cant for patients with TIA and stroke separately and was independent of known risk factors, but was not found for patients with acute coronary events. The mtDNA sub-haplogroup K was present in 8•7% of the total UK population controls and therefore confers a 4•0% (95% CI 2•2-5•7) reduction in population attributable risk of TIA and stroke. Interpretation Genetic variation of mtDNA sub-haplogroup K is an independent determinant of risk of cerebral, but not coronary, ischaemic vascular events. These fi ndings implicate mitochondrial mechanisms in the aetiology of ischaemic stroke and provide a new means for the identifi cation of individuals with a high susceptibility of developing ischaemic stroke.

Research paper thumbnail of Lack of Predictive Value of High Shear Platelet Function in a Population Based Cohort Study of Acute Vascular Events

Journal of Thrombosis and Haemostasis, 2007

Research paper thumbnail of Alzheimer's Disease and the Eye☆

Journal of Optometry, 2009

Dementia, including Alzheimer's disease (AD), is a major disorder causing visual problems in the ... more Dementia, including Alzheimer's disease (AD), is a major disorder causing visual problems in the elderly population. The pathology of AD includes the deposition in the brain of abnormal aggregates of β-amyloid (Aβ) in the form of senile plaques (SP) and abnormally phosphorylated tau in the form of neurofibrillary tangles (NFT). A variety of visual problems have been reported in patients with AD including loss of visual acuity (VA), colour vision and visual fields; changes in pupillary response to mydriatics, defects in fixation and in smooth and saccadic eye movements; changes in contrast sensitivity and in visual evoked potentials (VEP); and disturbances of complex visual functions such as reading, visuospatial function, and in the naming and identification of objects. Many of these changes are controversial with conflicting data in the literature and no ocular or visual feature can be regarded as particularly diagnostic of AD. In addition, some pathological changes have been observed to affect the eye, visual pathway, and visual cortex in AD. The optometrist has a role in helping a patient with AD, if it is believed that signs and symptoms of the disease are present, so as to optimize visual function and improve the quality of life.

Research paper thumbnail of Histological Features of Symptomatic Carotid Plaques in Patients with Impaired Glucose Tolerance and Diabetes (Oxford Plaque Study)

Cerebrovascular Diseases, 2008

Background: Diabetes is associated with an increased risk of incident stroke and both early and l... more Background: Diabetes is associated with an increased risk of incident stroke and both early and late recurrent stroke after transient ischaemic attack. Some small studies have suggested that atherosclerotic plaques from diabetics have a higher prevalence of unstable features than plaques from non-diabetics but results have been inconsistent. Method: We made detailed histological assessments of 526 plaques from consecutive patients undergoing carotid endarterectomy for recently symptomatic stenosis and related these to the presence of diabetes and impaired glucose tolerance (IGT). Results: 53 (10.1%) patients had diabetes, 26 (5%) had IGT and 447 (84.9%) had normal glucose tolerance (NGT). The overall prevalence of unstable plaque features was similar across these groups. However, whereas plaques removed >60 days after last symptoms in patients with NGT had less surface thrombus (OR = 0.61, 95% CI = 0.40–0.92, p = 0.02), fewer plaque macrophages (OR = 0.78, 95% CI = 0.51–1.19, p &...

Research paper thumbnail of Large diameter optic nerve axon fibres in Alzheimer's disease

A variety of visual symptoms have been associated with Alzheimer's disease (AD). These includ... more A variety of visual symptoms have been associated with Alzheimer's disease (AD). These include delays in flash visual evoked potentials which indicate a disruption of the integrity of the visual pathway. Examination of the visual cortex has revealed the presence of both senile plaques and neurofibrillary tangles. The purpose of this study was to determine whether there were differences in the number and/or size of optic nerve axons between AD patients and non-demented age-matched controls. Five optic nerves from AD patients and five from age-matched controls were embedded in epon resin and 1 micron sections prepared on a Reichert ultramicrotome. The sections were then stained in toluidine blue and examined at x400 magnification. The numbers of axons were counted in photographs of three fields taken at random from each section. To evaluate the axon diameters, 70 axons were chosen at random from each patient and measured using a calibrated eyepiece graticule. The total axon counts revealed no significant differences between the AD optic nerves and the age-matched controls. However, the frequency distribution of axon diameters was significantly different in the two groups. In particular, there were fewer larger diameter axons in patients with AD as previously reported. Degeneration of the large diameter axons suggests involvement of the magnocellular as opposed to the parvocellular pathways. Hence, there could be differences in visual performance of AD patients compared with normals which could be important in clinical diagnosis.

Research paper thumbnail of Lack of association between aspirin responsiveness and seven candidate gene haplotypes in patients with symptomatic vascular disease

Thrombosis and haemostasis, 2009

We studied the effect of prophylactic aspirin (ASA) ingestion on platelet function in 463 patient... more We studied the effect of prophylactic aspirin (ASA) ingestion on platelet function in 463 patients with stroke, transient ischemic attack (TIA) or acute coronary disease (ACD), using the Platelet Function Analyzer-100 (PFA-100). We correlated ASA responsiveness with haplotypes of seven candidate genes, selected for their documented role in platelet function, namely, the genes for integrins alpha2beta1and alphaIIbbeta3 (ITGA2, ITGA2B, and ITGB3), platelet glycoproteins Ibalpha and VI (GPIBA and GP6), the purinergic receptor P2Y1 (P2RY1), and prostaglandin H synthase 1 (PTGS1 = COX1). Non-responsiveness to ASA was defined as the failure of prior ASA ingestion to prolong the PFA-100 closure time (CT) when blood was perfused through cartridges coated with collagen plus epinephrine (CEPI-CT). ASA non-responsiveness was observed in 114 of 463 patients (24.6 %), but was not associated with haplotypes of any of the seven candidate genes. There was also no association between any haplotypes ...

Research paper thumbnail of The incidence of corpora amylacea (CA) in the optic nerve of patients with Alzheimer's disease

Corpora amylacea (CA) are spherical or ovoid bodies 50-50 microns in diameter. They have been des... more Corpora amylacea (CA) are spherical or ovoid bodies 50-50 microns in diameter. They have been described in normal elderly brain as well as in a number of neurodegenerative disorders. In this study, the incidence of CA in the optic nerves of Alzheimer's disease (AD) patients was compared with normal elderly controls. Samples of optic nerves (MRC Brain Bank, Institute of Psychiatry) were taken from 12 AD patients (age range 69-94 years) and 18 controls (43-82 years). Optic nerves were fixed in 2% buffered glutaraldehyde, post-fixed in osmium tetroxide, embedded in epoxy resin and then sectioned to a thickness of 2 microns. Sections were stained with toluidine blue. CA were present in all of the optic nerves examined. In addition, a number of similarly stained but more irregularly shaped bodies were present. Fewer CA were found in the optic nerves of AD patients compared with controls. By contrast, the number or irregularly shaped bodies was increased in AD. In AD, there may be a p...

Research paper thumbnail of Quantification of axonal loss in Alzheimer’s disease: an image analysis study

The density of axons in the optic nerve, olfactory tract and corpus callosum was quantified in no... more The density of axons in the optic nerve, olfactory tract and corpus callosum was quantified in non-demented elderly subjects and in Alzheimer’s disease (AD) using an image analysis system. In each fibre tract, there was significant reduction in the density of axons in AD compared with non-demented subjects, the greatest reductions being observed in the olfactory tract and corpus callosum. Axonal loss in the optic nerve and olfactory tract was mainly of axons with smaller myelinated cross-sectional areas. In the corpus callosum, a reduction in the number of ‘thin’ and ‘thick’ fibres was observed in AD, but there was a proportionally greater loss of the ‘thick’ fibres. The data suggest significant degeneration of white matter fibre tracts in AD involving the smaller axons in the two sensory nerves and both large and small axons in the corpus callosum. Loss of axons in AD could reflect an associated white matter disorder and/or be secondary to neuronal degeneration.

Research paper thumbnail of A quantitative analysis of optic nerve axons in elderly control subjects and patients with Alzheimer's disease

Folia neuropathologica / Association of Polish Neuropathologists and Medical Research Centre, Polish Academy of Sciences, 2005

To study the density and cross-sectional area of axons in the optic nerve in elderly control subj... more To study the density and cross-sectional area of axons in the optic nerve in elderly control subjects and in cases of Alzheimer's disease (AD) using an image analysis system. Sections of optic nerves from control and AD patients were stained with toluidine blue to reveal axon profiles. The density of axons was reduced in both the center and peripheral portions of the optic nerve in AD compared with control patients. Analysis of axons with different cross-sectional areas suggested a specific loss of the smaller sized axons in AD, i.e., those with areas less that 1.99 microm2. An analysis of axons >11 microm2 in cross-sectional area suggested no specific loss of the larger axons in this group of patients. The data suggest that image analysis provides an accurate and reproducible method of quantifying axons in the optic nerve. In addition, the data suggest that axons are lost throughout the optic nerve with a specific loss of the smaller-sized axons. Loss of the smaller axons ma...

Research paper thumbnail of Lack of reproducibility of assessment of aspirin responsiveness by optical aggregometry and two platelet function tests

Platelets, 2008

The term aspirin-resistance describes the failure of aspirin to inhibit thromboxane A(2) producti... more The term aspirin-resistance describes the failure of aspirin to inhibit thromboxane A(2) production. Many new tests have become available for potentially measuring aspirin responses but some are non-specific and do not isolate COX-1 activity. We previously demonstrated that agreement between two tests (PFA-100 and VerifyNow-ASA) and light transmission aggregation (LTA) was no greater than would be expected by chance. In this study we re-tested the same patients using identical methods after 1 year to determine whether poor agreement might have been due to assessment in the acute phase and whether the results of the individual tests are consistent over time. Platelet function by all three tests was re-tested in the 72 patients who were alive and still receiving low dose ASA therapy one year after the first tests were performed. On re-testing the prevalence of ASA non-responsiveness compared with baseline was 10% vs 17% by the VerifyNow-ASA test, 25% vs 22% by the PFA-100(R), and 1% vs 5% by LTA. Agreement between the tests at 1 year remained poor (kappas: 0.02-0.17) and only one patient was identified as a non-responder by all three tests, in keeping with the theoretical differences between the tests. Within test comparisons of baseline vs 1 year showed moderate agreement for the PFA-100(R) (kappa = 0.44, 95% CI 0.19-0.68, p = 0.0006), a fair agreement for VerifyNow-ASA (kappa = 0.34, 0.04-0.64, p = 0.12) and poor agreement for LTA (kappa = 0.14, -0.11 -0.39, p = 0.24 for ADP; kappa = 0.09, -0.21-0.39, p = 0.41 for arachidonic acid). Agreement between the three tests in identifying aspirin non-responsiveness remained poor in patients who had been taking aspirin for at least 1 year follow-up. Reproducibility over time was no greater than chance for LTA and only moderate for VerifyNow-ASA and PFA-100(R). Lack of consistency over time in identification of apparently non-responsiveness individuals is likely to substantially undermine any ability of these tests to predict risk of recurrent vascular events.

Research paper thumbnail of Density and cross-sectional areas of axons in the olfactory tract in control subjects and Alzheimer’s disease: an image analysis study

Neurological Sciences, 2008

Using an image analysis system to determine whether there is loss of axons in the olfactory tract... more Using an image analysis system to determine whether there is loss of axons in the olfactory tract (OT) in Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD). A retrospective neuropathological study. Nine control patients and eight clinically and pathologically verified AD cases. There was a reduction in axon density in AD compared with control subjects in the central and peripheral regions of the tract. Axonal loss was mainly of axons with smaller (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;2.99 microm(2)) myelinated cross-sectional areas. The data suggest significant degeneration of axons within the OT involving the smaller sized axons. Loss of axons in the OT is likely to be secondary to pathological changes originating within the parahippocampal gyrus rather than to a pathogen spreading into the brain via the olfactory pathways.

Research paper thumbnail of Mitochondrial DNA haplogroups and risk of transient ischaemic attack and ischaemic stroke: a genetic association study

The Lancet Neurology, 2010

Background Genetic factors have a role in the pathogenesis of ischaemic stroke, but the main gene... more Background Genetic factors have a role in the pathogenesis of ischaemic stroke, but the main genes involved have yet to be defi ned. Mitochondrial mechanisms have been implicated in the pathophysiology of acute stroke, but the role of mitochondrial DNA (mtDNA) has not been comprehensively studied. We investigated whether there is an association between mtDNA haplotypes and incidence of stroke. Methods The major European mtDNA haplogroups were identifi ed in two independent subpopulations (n=950) from a study of occurrence of transient ischaemic attack (TIA) and ischaemic stroke and were compared with those of patients with acute coronary syndromes from the same populations (n=340) and with those of independent population controls (n=2939). Findings The presence of mtDNA sub-haplogroup K was signifi cantly less frequent in patients with TIA or stroke than in controls in both subpopulations separately and in a pooled analysis (odds ratio 0•54, 95% CI 0•39-0•75, p<0•00001). This association remained highly signifi cant after adjustment for multiple haplogroup comparisons. The association was signifi cant for patients with TIA and stroke separately and was independent of known risk factors, but was not found for patients with acute coronary events. The mtDNA sub-haplogroup K was present in 8•7% of the total UK population controls and therefore confers a 4•0% (95% CI 2•2-5•7) reduction in population attributable risk of TIA and stroke. Interpretation Genetic variation of mtDNA sub-haplogroup K is an independent determinant of risk of cerebral, but not coronary, ischaemic vascular events. These fi ndings implicate mitochondrial mechanisms in the aetiology of ischaemic stroke and provide a new means for the identifi cation of individuals with a high susceptibility of developing ischaemic stroke.

Research paper thumbnail of Lack of Predictive Value of High Shear Platelet Function in a Population Based Cohort Study of Acute Vascular Events

Journal of Thrombosis and Haemostasis, 2007

Research paper thumbnail of Alzheimer's Disease and the Eye☆

Journal of Optometry, 2009

Dementia, including Alzheimer's disease (AD), is a major disorder causing visual problems in the ... more Dementia, including Alzheimer's disease (AD), is a major disorder causing visual problems in the elderly population. The pathology of AD includes the deposition in the brain of abnormal aggregates of β-amyloid (Aβ) in the form of senile plaques (SP) and abnormally phosphorylated tau in the form of neurofibrillary tangles (NFT). A variety of visual problems have been reported in patients with AD including loss of visual acuity (VA), colour vision and visual fields; changes in pupillary response to mydriatics, defects in fixation and in smooth and saccadic eye movements; changes in contrast sensitivity and in visual evoked potentials (VEP); and disturbances of complex visual functions such as reading, visuospatial function, and in the naming and identification of objects. Many of these changes are controversial with conflicting data in the literature and no ocular or visual feature can be regarded as particularly diagnostic of AD. In addition, some pathological changes have been observed to affect the eye, visual pathway, and visual cortex in AD. The optometrist has a role in helping a patient with AD, if it is believed that signs and symptoms of the disease are present, so as to optimize visual function and improve the quality of life.

Research paper thumbnail of Histological Features of Symptomatic Carotid Plaques in Patients with Impaired Glucose Tolerance and Diabetes (Oxford Plaque Study)

Cerebrovascular Diseases, 2008

Background: Diabetes is associated with an increased risk of incident stroke and both early and l... more Background: Diabetes is associated with an increased risk of incident stroke and both early and late recurrent stroke after transient ischaemic attack. Some small studies have suggested that atherosclerotic plaques from diabetics have a higher prevalence of unstable features than plaques from non-diabetics but results have been inconsistent. Method: We made detailed histological assessments of 526 plaques from consecutive patients undergoing carotid endarterectomy for recently symptomatic stenosis and related these to the presence of diabetes and impaired glucose tolerance (IGT). Results: 53 (10.1%) patients had diabetes, 26 (5%) had IGT and 447 (84.9%) had normal glucose tolerance (NGT). The overall prevalence of unstable plaque features was similar across these groups. However, whereas plaques removed >60 days after last symptoms in patients with NGT had less surface thrombus (OR = 0.61, 95% CI = 0.40–0.92, p = 0.02), fewer plaque macrophages (OR = 0.78, 95% CI = 0.51–1.19, p &...

Research paper thumbnail of Large diameter optic nerve axon fibres in Alzheimer's disease

A variety of visual symptoms have been associated with Alzheimer's disease (AD). These includ... more A variety of visual symptoms have been associated with Alzheimer's disease (AD). These include delays in flash visual evoked potentials which indicate a disruption of the integrity of the visual pathway. Examination of the visual cortex has revealed the presence of both senile plaques and neurofibrillary tangles. The purpose of this study was to determine whether there were differences in the number and/or size of optic nerve axons between AD patients and non-demented age-matched controls. Five optic nerves from AD patients and five from age-matched controls were embedded in epon resin and 1 micron sections prepared on a Reichert ultramicrotome. The sections were then stained in toluidine blue and examined at x400 magnification. The numbers of axons were counted in photographs of three fields taken at random from each section. To evaluate the axon diameters, 70 axons were chosen at random from each patient and measured using a calibrated eyepiece graticule. The total axon counts revealed no significant differences between the AD optic nerves and the age-matched controls. However, the frequency distribution of axon diameters was significantly different in the two groups. In particular, there were fewer larger diameter axons in patients with AD as previously reported. Degeneration of the large diameter axons suggests involvement of the magnocellular as opposed to the parvocellular pathways. Hence, there could be differences in visual performance of AD patients compared with normals which could be important in clinical diagnosis.

Research paper thumbnail of Lack of association between aspirin responsiveness and seven candidate gene haplotypes in patients with symptomatic vascular disease

Thrombosis and haemostasis, 2009

We studied the effect of prophylactic aspirin (ASA) ingestion on platelet function in 463 patient... more We studied the effect of prophylactic aspirin (ASA) ingestion on platelet function in 463 patients with stroke, transient ischemic attack (TIA) or acute coronary disease (ACD), using the Platelet Function Analyzer-100 (PFA-100). We correlated ASA responsiveness with haplotypes of seven candidate genes, selected for their documented role in platelet function, namely, the genes for integrins alpha2beta1and alphaIIbbeta3 (ITGA2, ITGA2B, and ITGB3), platelet glycoproteins Ibalpha and VI (GPIBA and GP6), the purinergic receptor P2Y1 (P2RY1), and prostaglandin H synthase 1 (PTGS1 = COX1). Non-responsiveness to ASA was defined as the failure of prior ASA ingestion to prolong the PFA-100 closure time (CT) when blood was perfused through cartridges coated with collagen plus epinephrine (CEPI-CT). ASA non-responsiveness was observed in 114 of 463 patients (24.6 %), but was not associated with haplotypes of any of the seven candidate genes. There was also no association between any haplotypes ...