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1.
Sci Rep ; 9(1): 10402, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31320653

RESUMO

Fast Field-Cycling (FFC) is a well-established Nuclear Magnetic Resonance (NMR) technique that exploits varying magnetic fields to quantify molecular motion over a wide range of time scales, providing rich structural information from nanometres to micrometres, non-invasively. Previous work demonstrated great potential for FFC-NMR biomarkers in medical applications; our research group has now ported this technology to medical imaging by designing a whole-body FFC Magnetic Resonance Imaging (FFC-MRI) scanner capable of performing accurate measurements non-invasively over the entire body, using signals from water and fat protons. This is a unique tool to explore new biomarkers related to disease-induced tissue remodelling. Our approach required making radical changes in the design, construction and control of MRI hardware so that the magnetic field is switched within 12.5 ms to reach any field strength from 50 µT to 0.2 T, providing clinically useful images within minutes. Pilot studies demonstrated endogenous field-dependant contrast in biological tissues in good agreement with reference data from other imaging modalities, confirming that our system can perform multiscale structural imaging of biological tissues, from nanometres to micrometres. It is now possible to confirm ex vivo results obtained from previous clinical studies, offering applications in diagnosis, staging and monitoring treatment for cancer, stroke, osteoarthritis and oedema.

2.
Kidney Int Rep ; 3(5): 1064-1076, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30197973

RESUMO

Introduction: Stroke rate and mortality are greater in individuals with end-stage renal disease (ESRD) than in those without ESRD. We examined discrepancies in stroke care in ESRD patients and their influence on mortality. Methods: This is a national record linkage cohort study of hospitalized stroke individuals from 2005 to 2013. Presentation, measures of care quality (admission to stroke unit, swallow assessment, antithrombotics, or thrombolysis use), and outcomes were compared in those with and without ESRD after propensity score matching (PSM). We examined the effect of being admitted to a stroke unit on survival using Kaplan-Meier and Cox survival analyses. Results: A total of 8757 individuals with ESRD and 61,367 individuals with stroke were identified. ESRD patients (n =486) experienced stroke over 34,551.9 patient-years of follow-up; incidence rates were 25.3 (dialysis) and 4.5 (kidney transplant)/1000 patient-years. After PSM, dialysis patients were less likely to be functionally independent (61.4% vs. 77.7%; P < 0.0001) before stroke, less frequently admitted to stroke units (64.6% vs. 79.6%; P < 0.001), or to receive aspirin (75.3% vs. 83.2%; P = 0.01) than non-ESRD stroke patients. There were no significant differences in management of kidney transplantation patients. Stroke with ESRD was associated with a higher death rate during admission (dialysis 22.9% vs.14.4%, P = 0.002; transplantation: 19.6% vs. 9.3%; P = 0.034). Managing ESRD patients in a stroke unit was associated with a lower risk of death at follow-up (hazard ratio: 0.68; 95% confidence interval: 0.55-0.84). Conclusion: Stroke incidence is high in ESRD. Individuals on dialysis are functionally more dependent before stroke and less frequently receive optimal stroke care. After a stroke, death is more likely in ESRD patients. Acute stroke unit care may be associated with lower mortality.

3.
Lancet ; 391(10134): 2019-2027, 2018 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-29864018

RESUMO

BACKGROUND: Stroke disproportionately affects people in low-income and middle-income countries. Although improvements in stroke care and outcomes have been reported in high-income countries, little is known about practice and outcomes in low and middle-income countries. We aimed to compare patterns of care available and their association with patient outcomes across countries at different economic levels. METHODS: We studied the patterns and effect of practice variations (ie, treatments used and access to services) among participants in the INTERSTROKE study, an international observational study that enrolled 13 447 stroke patients from 142 clinical sites in 32 countries between Jan 11, 2007, and Aug 8, 2015. We supplemented patient data with a questionnaire about health-care and stroke service facilities at all participating hospitals. Using univariate and multivariate regression analyses to account for patient casemix and service clustering, we estimated the association between services available, treatments given, and patient outcomes (death or dependency) at 1 month. FINDINGS: We obtained full information for 12 342 (92%) of 13 447 INTERSTROKE patients, from 108 hospitals in 28 countries; 2576 from 38 hospitals in ten high-income countries and 9766 from 70 hospitals in 18 low and middle-income countries. Patients in low-income and middle-income countries more often had severe strokes, intracerebral haemorrhage, poorer access to services, and used fewer investigations and treatments (p<0·0001) than those in high-income countries, although only differences in patient characteristics explained the poorer clinical outcomes in low and middle-income countries. However across all countries, irrespective of economic level, access to a stroke unit was associated with improved use of investigations and treatments, access to other rehabilitation services, and improved survival without severe dependency (odds ratio [OR] 1·29; 95% CI 1·14-1·44; all p<0·0001), which was independent of patient casemix characteristics and other measures of care. Use of acute antiplatelet treatment was associated with improved survival (1·39; 1·12-1·72) irrespective of other patient and service characteristics. INTERPRETATION: Evidence-based treatments, diagnostics, and stroke units were less commonly available or used in low and middle-income countries. Access to stroke units and appropriate use of antiplatelet treatment were associated with improved recovery. Improved care and facilities in low-income and middle-income countries are essential to improve outcomes. FUNDING: Chest, Heart and Stroke Scotland.


Assuntos
Padrões de Prática Médica , Acidente Vascular Cerebral/terapia , Idoso , Estudos de Casos e Controles , Países Desenvolvidos , Países em Desenvolvimento , Medicina Baseada em Evidências , Feminino , Acesso aos Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Pobreza , Inquéritos e Questionários , Análise de Sobrevida , Resultado do Tratamento
4.
Artigo em Inglês | MEDLINE | ID: mdl-29069522

RESUMO

Background: The risk of stroke in end-stage renal disease (ESRD) on renal replacement therapy (RRT) is up to 10-fold greater than the general population. However, whether this increased risk differs by RRT modality is unclear. Methods: We used data contained in the Scottish Renal Registry and the Scottish Stroke Care Audit to identify stroke in all adult patients who commenced RRT for ESRD from 2005 to 2013. Incidence rate was calculated and regression analyses were performed to identify variables associated with stroke. We explored the effect of RRT modality at initiation and cumulative dialysis exposure by time-dependent regression analysis, using transplant recipients as the reference group. Results: A total of 4957 patients commenced RRT for ESRD. Median age was 64.5 years, 41.5% were female and 277 patients suffered a stroke (incidence rate was 18.6/1000 patient-years). Patients who had stroke were older, had higher blood pressure and were more likely to be female and have diabetes. On multivariable regression older age, female sex, diabetes and higher serum phosphate were associated with risk of stroke. RRT modality at initiation was not. On time-dependent analysis, haemodialysis (HD) exposure was independently associated with increased risk of stroke. Conclusions: In patients with ESRD who initiate RRT, HD use independently increases risk of stroke compared with transplantation. Use of peritoneal dialysis did not increase risk on adjusted analysis.

5.
Trials ; 18(1): 162, 2017 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-28381307

RESUMO

BACKGROUND: Recruitment to randomised prevention trials is challenging, not least for intracerebral haemorrhage (ICH) associated with antithrombotic drug use. We investigated reasons for not recruiting apparently eligible patients at hospital sites that keep screening logs in the ongoing REstart or STop Antithrombotics Randomised Trial (RESTART), which seeks to determine whether to start antiplatelet drugs after ICH. METHOD: By the end of May 2015, 158 participants had been recruited at 108 active sites in RESTART. The trial coordinating centre invited all sites that kept screening logs to submit screening log data, followed by one reminder. We checked the integrity of data, focused on the completeness of data about potentially eligible patients and categorised the reasons they were not randomised. RESULTS: Of 108 active sites, 39 (36%) provided usable screening log data over a median of ten (interquartile range = 5-13) months of recruitment per site. During this time, sites screened 633 potentially eligible patients and randomised 53 (8%) of them. The main reasons why 580 patients were not randomised were: 43 (7%) patients started anticoagulation, 51 (9%) patients declined, 148 (26%) patients' stroke physicians were not uncertain about using antiplatelet drugs, 162 (28%) patients were too unwell and 176 (30%) patients were not randomised due to other reasons. CONCLUSION: RESTART recruited ~8% of eligible patients. If more physicians were uncertain about the therapeutic dilemma that RESTART is addressing, RESTART could have recruited up to four times as many participants. The trial coordinating centre continues to engage with physicians about their uncertainty. TRIAL REGISTRATION: EU Clinical Trials, EudraCT 2012-003190-26 . Registered on 3 July 2012.


Assuntos
Hemorragia Cerebral/prevenção & controle , Definição da Elegibilidade , Fibrinolíticos/efeitos adversos , Seleção de Pacientes , Inibidores da Agregação de Plaquetas/efeitos adversos , Pesquisadores , Tamanho da Amostra , Prevenção Secundária/métodos , Atitude do Pessoal de Saúde , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/diagnóstico , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Papel do Médico , Reino Unido
6.
Age Ageing ; 46(3): 421-426, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-27810853

RESUMO

Introduction: physicians are often asked to prognosticate soon after a patient presents with stroke. This study aimed to compare two outcome prediction scores (Five Simple Variables [FSV] score and the PLAN [Preadmission comorbidities, Level of consciousness, Age, and focal Neurologic deficit]) with informal prediction by physicians. Methods: demographic and clinical variables were prospectively collected from consecutive patients hospitalised with acute ischaemic or haemorrhagic stroke (2012-13). In-person or telephone follow-up at 6 months established vital and functional status (modified Rankin score [mRS]). Area under the receiver operating curves (AUC) was used to establish prediction score performance. Results: five hundred and seventy-five patients were included; 46% female, median age 76 years, 88% ischaemic stroke. Six months after stroke, 47% of patients had a good outcome (alive and independent, mRS 0-2) and 26% a devastating outcome (dead or severely dependent, mRS 5-6). The FSV and PLAN scores were superior to physician prediction (AUCs of 0.823-0.863 versus 0.773-0.805, P < 0.0001) for good and devastating outcomes. The FSV score was superior to the PLAN score for predicting good outcomes and vice versa for devastating outcomes (P < 0.001). Outcome prediction was more accurate for those with later presentations (>24 hours from onset). Conclusion: the FSV and PLAN scores are validated in this population for outcome prediction after both ischaemic and haemorrhagic stroke. The FSV score is the least complex of all developed scores and can assist outcome prediction by physicians.


Assuntos
Isquemia Encefálica/diagnóstico , Técnicas de Apoio para a Decisão , Médicos , Acidente Vascular Cerebral/diagnóstico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/psicologia , Isquemia Encefálica/terapia , Comorbidade , Estado de Consciência , Avaliação da Deficiência , Feminino , Avaliação Geriátrica , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Escócia , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/psicologia , Acidente Vascular Cerebral/terapia , Reabilitação do Acidente Vascular Cerebral , Fatores de Tempo
8.
BMC Res Notes ; 7: 728, 2014 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-25322939

RESUMO

BACKGROUND: Although pontine strokes account for a small percentage of all ischaemic events, they can be associated with significant initial disability. These lesions may be missed on computed tomography and therefore magnetic resonance imaging is generally preferred for the assessment of brainstem strokes. The aetiopathogenesis of isolated pontine infarcts, not due to a significant compromise (occlusion or dissection) in the vertebrobasilar territory, still remains to be fully characterised. These strokes present with different symptoms, depending on the lesion location and size, partly reflecting the anatomical variability of the vertebrobasilar vessels. Progressive neurological deterioration is relatively common and has been associated with the extension of such lesions. However, many patients with significant infarcts in the pons will do well in the future and initial diffusion-weighted imaging may not add useful prognostication to the clinical assessment. We discuss here a case where an initially progressive presentation was associated with a marked improvement in both clinical and radiological assessments at 42 days. CASE PRESENTATION: A 49-year-old white British man presented with left-sided weakness, incoordination, unsteadiness, cerebellar ataxic dysarthria and dysphonia. A baseline magnetic resonance imaging scan with diffusion-weighted imaging, T1-weighted and T2-weighted sequences showed an acute bilateral pontine infarct. On a repeat scan at 42 days, there was a 57.5% decrease in the size of the lesion on the high-resolution three-dimensional T1-weighted image and a corresponding improvement in the symptoms and the clinical assessments of this patient. The reduction in infarct size was also comparable to the decrease calculated between the baseline diffusion-weighted and the follow-up fluid attenuated inversion recovery sequences. CONCLUSION: This case report discusses the significant clinical improvement and corresponding lesion reduction in a patient that presented with worsening neurological symptoms and was diagnosed with acute bilateral ischaemic pontine infarction. Further studies, utilising structural and functional magnetic resonance imaging with follow-up scans, are needed to provide better insights into the underlying aetiopathology and recovery mechanisms of pontine stroke. These will help define the relationship between imaging parameters and outcome allowing for better prognosis along with the development of relevant rehabilitation programs for this group of patients.


Assuntos
Isquemia Encefálica/diagnóstico , Imagem de Difusão por Ressonância Magnética , Ponte/irrigação sanguínea , Acidente Vascular Cerebral/diagnóstico , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/reabilitação , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/fisiopatologia , Reabilitação do Acidente Vascular Cerebral , Fatores de Tempo , Resultado do Tratamento
9.
J Neuroimaging ; 24(6): 562-568, 2014 Nov-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25039499

RESUMO

BACKGROUND AND PURPOSE: Computed tomography perfusion provides information on tissue viability according to proposed thresholds. We evaluated thresholds for ischemic core and tissue at risk and subsequently tested their accuracy in independent datasets. MATERIALS AND METHODS: Tissue at risk was evaluated in patients with persistent arterial occlusions, and ischemic core thresholds in patients with recanalization and major clinical improvement. Scans were randomly allocated to derivation or validation groups for tissue at risk and core analysis. Optimum thresholds using mean transit time (MTT), cerebral blood flow (CBF), cerebral blood volume, and delay time (DT) were assessed. RESULTS: Absolute MTT, relative MTT and DT were best derived predictors of tissue at risk with thresholds of ≥ 7 seconds, ≥ 125%, and ≥ 2 seconds respectively. DT ≥ 2 seconds was the best predictor in the validation dataset (95% agreement levels = -44 to +30 mL, Bias = -6.9). Absolute and relative MTT were the best derived predictors of infarct volume in the core group (8 seconds and 125% respectively) but relative CBF of ≤ 45% performed best in the core validation dataset. CONCLUSIONS: Time-based perfusion thresholds perform well as predictors of tissue at risk of infarction with DT the best predictor. Relative CBF was the best predictor of ischemic core. Evaluation in larger populations is needed to confirm the performance of tissue viability thresholds.


Assuntos
Velocidade do Fluxo Sanguíneo , Angiografia Cerebral/métodos , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/fisiopatologia , Circulação Cerebrovascular , Angiografia por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Medição de Risco/métodos , Escócia , Sensibilidade e Especificidade
10.
PLoS One ; 9(1): e79802, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24404122

RESUMO

OBJECTIVES: Study objectives were to investigate the prevalence and causes of prescribing errors amongst foundation doctors (i.e. junior doctors in their first (F1) or second (F2) year of post-graduate training), describe their knowledge and experience of prescribing errors, and explore their self-efficacy (i.e. confidence) in prescribing. METHOD: A three-part mixed-methods design was used, comprising: prospective observational study; semi-structured interviews and cross-sectional survey. All doctors prescribing in eight purposively selected hospitals in Scotland participated. All foundation doctors throughout Scotland participated in the survey. The number of prescribing errors per patient, doctor, ward and hospital, perceived causes of errors and a measure of doctors' self-efficacy were established. RESULTS: 4710 patient charts and 44,726 prescribed medicines were reviewed. There were 3364 errors, affecting 1700 (36.1%) charts (overall error rate: 7.5%; F1:7.4%; F2:8.6%; consultants:6.3%). Higher error rates were associated with : teaching hospitals (p<0.001), surgical (p = <0.001) or mixed wards (0.008) rather thanmedical ward, higher patient turnover wards (p<0.001), a greater number of prescribed medicines (p<0.001) and the months December and June (p<0.001). One hundred errors were discussed in 40 interviews. Error causation was multi-factorial; work environment and team factors were particularly noted. Of 548 completed questionnaires (national response rate of 35.4%), 508 (92.7% of respondents) reported errors, most of which (328 (64.6%) did not reach the patient. Pressure from other staff, workload and interruptions were cited as the main causes of errors. Foundation year 2 doctors reported greater confidence than year 1 doctors in deciding the most appropriate medication regimen. CONCLUSIONS: Prescribing errors are frequent and of complex causation. Foundation doctors made more errors than other doctors, but undertook the majority of prescribing, making them a key target for intervention. Contributing causes included work environment, team, task, individual and patient factors. Further work is needed to develop and assess interventions that address these.


Assuntos
Prescrições de Medicamentos/estatística & dados numéricos , Prescrições de Medicamentos/normas , Erros de Medicação/estatística & dados numéricos , Médicos/normas , Competência Clínica , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Estudos Prospectivos , Autoeficácia , Inquéritos e Questionários
11.
Proc Natl Acad Sci U S A ; 110(45): 18333-8, 2013 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-24145420

RESUMO

Significantly above-chance detection of stimuli presented within the field defect of patients with postgeniculate lesions is termed "blindsight." It has been proposed that those with blindsight are more likely to benefit from visual rehabilitation by repeated stimulation, leading to increased visual sensitivity within their field defect. Establishing the incidence of blindsight and developing an objective and reliable method for its detection are of great interest. Sudden onsets of a grating pattern in the absence of any change in light flux result in a transient constriction of the pupil, termed "pupil grating response." The existence of pupil grating responses for stimuli presented within the blindfield has previously been reported in a hemianopic patient and two monkeys with removal of the primary visual cortex unilaterally. Here, we have systematically investigated the presence of a spatial channel of processing at a range of spatial frequencies using a psychophysical forced-choice technique and obtained the corresponding pupil responses in the blindfield of 19 hemianopic patients. In addition, in 13 cases we determined the pupil responses in a sighted field location that matched the blindfield eccentricities. Our findings demonstrate that blindfield pupil responses are similar to those for the sighted field, but attenuated in amplitude. Pupillometry correctly characterized the presence or absence of a significant psychophysical response and thus is worth measuring in the cortically blindfields as a predictor of intact psychophysical capacity. The incidence of blindsight where detection performance had been investigated psychophysically over a range of spatial frequencies was 70%.


Assuntos
Hemianopsia/fisiopatologia , Pupila/fisiologia , Visão Ocular/fisiologia , Humanos , Estimulação Luminosa , Psicofísica , Escócia
12.
Br J Clin Pharmacol ; 76(6): 980-7, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23627415

RESUMO

AIMS: The aim of the study was to explore and compare junior doctors' perceptions of their self-efficacy in prescribing, their prescribing errors and the possible causes of those errors. METHODS: A cross-sectional questionnaire study was distributed to foundation doctors throughout Scotland, based on Bandura's Social Cognitive Theory and Human Error Theory (HET). RESULTS: Five hundred and forty-eight questionnaires were completed (35.0% of the national cohort). F1s estimated a higher daytime error rate [median 6.7 (IQR 2-12.4)] than F2s [4.0 IQR (0-10) (P = 0.002)], calculated based on the total number of medicines prescribed. The majority of self-reported errors (250, 49.2%) resulted from unintentional actions. Interruptions and pressure from other staff were commonly cited causes of errors. F1s were more likely to report insufficient prescribing skills as a potential cause of error than F2s (P = 0.002). The prescribers did not believe that the outcomes of their errors were serious. F2s reported higher self-efficacy scores than F1s in most aspects of prescribing (P < 0.001). CONCLUSION: Foundation doctors were aware of their prescribing errors, yet were confident in their prescribing skills and apparently complacent about the potential consequences of prescribing errors. Error causation is multi-factorial often due to environmental factors, but with lack of knowledge also contributing. Therefore interventions are needed at all levels, including environmental changes, improving knowledge, providing feedback and changing attitudes towards the role of prescribing as a major influence on patient outcome.


Assuntos
Competência Clínica/normas , Prescrições de Medicamentos/normas , Erros de Medicação/psicologia , Padrões de Prática Médica/normas , Autoeficácia , Atitude do Pessoal de Saúde , Competência Clínica/estatística & dados numéricos , Estudos Transversais , Prescrições de Medicamentos/estatística & dados numéricos , Erros de Medicação/estatística & dados numéricos , Padrões de Prática Médica/tendências , Escócia , Inquéritos e Questionários , Carga de Trabalho
13.
BMJ Qual Saf ; 22(2): 97-102, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23112288

RESUMO

INTRODUCTION: Prescribing errors are a major cause of patient safety incidents. Understanding the underlying factors is essential in developing interventions to address this problem. This study aimed to investigate the perceived causes of prescribing errors among foundation (junior) doctors in Scotland. METHODS: In eight Scottish hospitals, data on prescribing errors were collected by ward pharmacists over a 14-month period. Foundation doctors responsible for making a prescribing error were interviewed about the perceived causes. Interview transcripts were analysed using content analysis and categorised into themes previously identified under Reason's Model of Accident Causation and Human Error. RESULTS: 40 prescribers were interviewed about 100 specific errors. Multiple perceived causes for all types of error were identified and were categorised into five categories of error-producing conditions, (environment, team, individual, task and patient factors). Work environment was identified as an important aspect by all doctors, especially workload and time pressures. Team factors included multiple individuals and teams involved with a patient, poor communication, poor medicines reconciliation and documentation and following incorrect instructions from other members of the team. A further team factor was the assumption that another member of the team would identify any errors made. The most frequently noted individual factors were lack of personal knowledge and experience. The main task factor identified was poor availability of drug information at admission and the most frequently stated patient factor was complexity. CONCLUSIONS: This study has emphasised the complex nature of prescribing errors, and the wide range of error-producing conditions within hospitals including the work environment, team, task, individual and patient. Further work is now needed to develop and assess interventions that address these possible causes in order to reduce prescribing error rates.


Assuntos
Causalidade , Competência Clínica/normas , Pacientes Internados , Erros de Medicação/psicologia , Médicos/psicologia , Padrões de Prática Médica/normas , Barreiras de Comunicação , Prescrições de Medicamentos/normas , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Entrevistas como Assunto , Masculino , Corpo Clínico Hospitalar/psicologia , Erros de Medicação/classificação , Erros de Medicação/prevenção & controle , Equipe de Assistência ao Paciente , Segurança do Paciente , Percepção , Relações Médico-Paciente , Pesquisa Qualitativa , Escócia/epidemiologia , Carga de Trabalho
15.
Neuropsychologia ; 46(3): 879-85, 2008 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-18158164

RESUMO

The term blindsight, coined by Larry Weiskrantz, describes those discrimination abilities that can be elicited with visual stimuli restricted to the blindfield of a patient with occipital brain lesion or damaged optic radiation. Over the past 3 decades, many aspects of blindsight have been investigated including detection of basic stimulus attributes such as structure, colour and movement as well as more complex tasks such as discrimination of facial expressions and semantic processing. The neuronal mechanisms mediating blindsight rely on processing in subcortical and/or extrastriate areas. It appears that following the occipital brain damage, there is a restricted "window of processing" and stimulus parameters mainly outside this window may not lead to blindsight performance. Here we report how the restricted "window of processing" appears to have a specific spatio-temporal response profile, mainly tuned to low spatial frequencies and intermediate temporal frequencies. In addition, in a group of blindsight patients, we demonstrate that above chance detection performance is related to the target size. The findings have implications both for the reported incidence of blindsight and development of rehabilitation strategies.


Assuntos
Mapeamento Encefálico , Discriminação (Psicologia)/fisiologia , Hemianopsia/patologia , Percepção Espacial/fisiologia , Córtex Visual/fisiopatologia , Campos Visuais/fisiologia , Adulto , Idoso , Comportamento de Escolha/fisiologia , Feminino , Hemianopsia/etiologia , Hemianopsia/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa/métodos , Psicofísica , Vias Visuais/patologia , Vias Visuais/fisiopatologia
16.
BMC Med Genet ; 8: 30, 2007 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-17553166

RESUMO

BACKGROUND: Ischaemic stroke is a common disorder with genetic and environmental components contributing to overall risk. Atherothromboembolic abnormalities, which play a crucial role in the pathogenesis of ischaemic stroke, are often the end result of dysregulation of lipid metabolism. The ATP Binding Cassette Transporter (ABCA1) is a key gene involved in lipid metabolism. It encodes the cholesterol regulatory efflux protein which mediates the transfer of cellular phospholipids and cholesterol to acceptor apolipoproteins such as apolipoprotein A-I (ApoA-I). Common polymorphisms in this gene affect High Density Lipoprotein Cholesterol (HDL-C) and Apolipoprotein A-I levels and so influence the risk of atherosclerosis. This study has assessed the distribution of ABCA1 polymorphisms and haplotype arrangements in patients with ischaemic stroke and compared them to an appropriate control group. It also examined the relationship of these polymorphisms with serum lipid profiles in cases and controls. METHODS: We studied four common polymorphisms in ABCA1 gene: G/A-L158L, G/A-R219K, G/A-G316G and G/A-R1587K in 400 Caucasian ischaemic stroke patients and 487 controls. Dynamic Allele Specific Hybridisation (DASH) was used as the genotyping assay. RESULTS: Genotype and allele frequencies of all polymorphisms were similar in cases and controls, except for a modest difference in the ABCA1 R219K allele frequency (P-value = 0.05). Using the PHASE2 program, haplotype frequencies for the four loci (158, 219, 316, and 1587) were estimated in cases and controls. There was no significant difference in overall haplotypes arrangement in patients group compared to controls (p = 0.27). 2211 and 1211 haplotypes (1 = common allele, 2 = rare allele) were more frequent in cases (p = 0.05). Adjusted ORs indicated 40% and 46% excess risk of stroke for these haplotypes respectively. However, none of the adjusted ORs were statistically significant. Individuals who had R219K "22" genotype had a higher LDL level (p = 0.001). CONCLUSION: Our study does not support a major role for the ABCA1 gene as a risk factor for ischaemic stroke. Some haplotypes may confer a minor amount of increased risk or protection. Polymorphisms in this gene may influence serum lipid profile.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Isquemia Encefálica/genética , Lipídeos/sangue , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/genética , Transportador 1 de Cassete de Ligação de ATP , Idoso , Alelos , Isquemia Encefálica/sangue , Feminino , Frequência do Gene , Marcadores Genéticos , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/sangue
17.
Proc Natl Acad Sci U S A ; 103(40): 14971-6, 2006 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-17000999

RESUMO

Lesions of the occipital cortex result in areas of cortical blindness affecting the corresponding regions of the patient's visual field. The traditional view is that, aside from some spontaneous recovery in the first few months after the damage, when acute effects have subsided the areas of blindness are absolute and permanent. It has been found, however, that within such field defects some residual visual capacities may persist in the absence of acknowledged awareness by the subject (blindsight type 1) or impaired awareness (type 2). Neuronal pathways mediating blindsight have a specific and narrow spatial and temporal bandwidth. A group of cortically blind patients (n = 12) carried out a daily detection "training" task over a 3-month period, discriminating grating visual stimuli optimally configured for blindsight from homogeneous luminance-matched stimuli. No feedback was given during the training. Assessment of training was by psychophysical measurements carried out before and after training and included detection of a range of spatial frequencies (0.5-7 cycles per degree), contrast detection at 1 cycle per degree, clinical perimetry, and subjective estimates of visual field defect. The results show that repeated stimulation by appropriate visual stimuli can result in improvements in visual sensitivities in the very depths of the field defect.


Assuntos
Cegueira Cortical/fisiopatologia , Percepção Visual/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Conscientização , Estudos de Casos e Controles , Sensibilidades de Contraste , Discriminação (Psicologia) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais , Estimulação Luminosa , Psicofísica , Testes de Campo Visual , Campos Visuais/fisiologia
18.
BMC Med Genet ; 7: 28, 2006 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-16551349

RESUMO

BACKGROUND: Paraoxonase (PON) has anti-atherogenic activity due to its protective function against low density lipoprotein (LDL) oxidation. Alteration of enzyme activity due to polymorphisms in the PON genes may influence the development of atheroma and thus affect stroke risk. Three PON genes (PON1, PON2 and PON3) have been identifiedand mapped to chromosome 7. METHODS: We looked at the distribution of paraoxonase polymorphisms and haplotype arrangement in 397 Caucasian ischaemic stroke patients and 405 controls. We investigated 6 different common single nucleotide polymorphisms (SNP) in PON genes; two substitutions in PON1 ["A/G": Gln (Q)/Arg (R)] at codon 192 and ["T/A": Leu (L)/Met (M)] at codon 55, two in PON2 at codon 311 ["G/A": Cys (C)/Ser (S)] and codon 148 ["C/G": Ala (A)/Gly (G)] and two SNPs, both "A" to "G" substitutions, in PON3--intronic rs2074353, which we designated PON3-1 and [Ala (A)/Ala (A)] at codon 99, designated as PON3-3. Dynamic Allele Specific Hybridisation (DASH) was used as the genotyping assay. Haplotype analysis was performed using both PHASE and EHPLUS programs. RESULTS: Genotype and allele frequencies were similar in cases and controls. Lipid profiles were not influenced by PON genotype. Haplotype frequencies for the six loci (PON2-148, PON2-311, PON3-3, PON3-1, PON1-55 and PON1-192) were estimated. Comparison of the two programs showed a significant difference in haplotype arrangements with EHPLUS (p-value = 0.005) but not with PHASE Ver.2 (p-value = 0.12). The 112211 (1 = frequent allele, 2 = rare allele) haplotype arrangement was commoner in cases than controls (p = 0.015), and the 111121 haplotype was commoner in controls (p = 0.006). CONCLUSION: Our study did not identify a role for individual paraoxonase gene polymorphisms in the pathogenesis of ischaemic stroke. Findings of haplotype differences should be confirmed in large scale studies. The importance of using a well-validated haplotype analysis program is also underlined.


Assuntos
Arildialquilfosfatase/genética , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/genética , Idoso , Estudos de Casos e Controles , Esterases/genética , Feminino , Frequência do Gene , Haplótipos , Humanos , Lipídeos/sangue , Masculino , Acidente Vascular Cerebral/diagnóstico
19.
Eur J Neurosci ; 18(5): 1189-96, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12956717

RESUMO

Blindsight is the ability of some cortically blind patients to discriminate visual events presented within their field defect. We have examined a fundamental aspect of visual processing, namely the detection of spatial structures presented within the field defect of 10 cortically blind patients. The method outlined is based on the detection of high-contrast stimuli and is effective in flagging a 'window of detection' in the spatial frequency spectrum, should it exist. Here we report on the presence of a narrowly tuned psychophysical spatial channel optimally responding to frequencies less than 4 cycles/ degrees in eight out of 10 patients tested. The two patients who did not show any evidence of blindsight appear to have intact midbrain structures, but have lesions that extend from the occipital cortex to the thalamus. In addition, we have recorded subjective reports of awareness of the visual events in each trial. Detection scores of eight blindsight patients were subsequently subdivided based on the subjective reports of awareness. It appears that the psychophysical spatial channel-mediating responses in the absence of any awareness of the visual event have a narrower frequency response than those involved when the patients report some awareness of the visual event. The findings are discussed in relation to previous reports on the incidence of blindsight and performance on tasks involving spatial processing.


Assuntos
Cegueira Cortical/fisiopatologia , Percepção Espacial/fisiologia , Campos Visuais/fisiologia , Adulto , Idoso , Conscientização , Mapeamento Encefálico , Sensibilidades de Contraste/fisiologia , Discriminação (Psicologia) , Feminino , Humanos , Imagem por Ressonância Magnética/instrumentação , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa
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