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Kennedy R Lees

Publications and source records attributed to Kennedy R Lees.

44 records · Page 3Linked to original sources
PubMed2003

Low triglyceride, not low cholesterol concentration, independently predicts poor outcome following acute stroke.

BACKGROUND: Recent data have shown an unexpected association between poor outcome after acute stroke and lower serum cholesterol. Triglyceride concentration has been linked to coronary heart disease and stroke; however, there are currently no data on the relationship between triglyceride and stroke outcome. Such information may yield further mechanistic information on the relationship between lipids and stroke outcome. METHODS: We studied 1,310 nondiabetic patients presenting to our acute stroke unit with computed tomography-confirmed acute stroke. Fasting blood samples were drawn within 24 h of admission for glucose, lipids and a standard battery of biochemistry and hematological tests. Information on age, stroke type, admission blood pressure, smoking status, presence of atrial fibrillation, resolution time of symptoms and Oxfordshire Community Stroke Project clinical classification was collated. Stepwise proportional hazards regression was used to estimate the effect of the above variables on survival following stroke. RESULTS: Increased age (p < 0.0001), presence of atrial fibrillation (p = 0.009), hyperglycemia (p = 0.0005) and lower triglyceride level (p < 0.0001) independently predicted higher mortality; early resolution of symptoms (p = 0.005) independently predicted lower mortality. Although serum cholesterol level predicted outcome after adjusting for other prognostic factors, it did not remain significant when triglyceride level was entered into the model. The relative hazard per additional quartile of triglyceride was 0.84 (95% confidence interval 0.77-0.91). CONCLUSIONS: Low triglyceride concentration strongly predicts higher mortality following stroke, whereas serum cholesterol level is not an independent predictor. Outcome following stroke is thus related more strongly to triglyceride-rich than to cholesterol-rich lipoprotein concentrations. The mechanisms explaining this require further investigation.

Acute Disease↗
PubMed2002

A multicentre observational study of presentation and early assessment of acute stroke.

OBJECTIVE: To investigate delays in the presentation to hospital and evaluation of patients with suspected stroke. DESIGN: Multicentre prospective observational study. SETTING: 22 hospitals in the United Kingdom and Dublin. PARTICIPANTS: 739 patients with suspected stroke presenting to hospital. MAIN OUTCOME MEASURES: Time from onset of stroke symptoms to arrival at hospital, and time from arrival to evaluation by a senior doctor. RESULTS: The median age of patients was 75 years, and 400 were women. The median delay between onset of symptoms and arrival at hospital was 6 hours (interquartile range 1 hour 48 minutes to 19 hours 12 minutes). 37% of patients arrived within 3 hours, 50% within 6 hours. The median delay for patients using the emergency service was 2 hours 3 minutes (47 minutes to 7 hours 12 minutes) compared with 7 hours 12 minutes (2 hours 5 minutes to 20 hours 37 minutes) for referrals from general practitioners (P<0.0001). Use of emergency services reduced delays to hospital (odds ratio 0.45, 95% confidence interval 0.23 to 0.61). The median time to evaluation by a senior doctor was 1 hour 9 minutes (interquartile range 33 minutes to 1 hour 50 minutes) but was undertaken in only 477 (65%) patients within 3 hours of arrival. This was not influenced by age, sex, time of presentation, mode of referral, hospital type, or the presence of a stroke unit. Computed tomography was requested within 3 hours of arrival in 166 (22%) patients but undertaken in only 60 (8%). CONCLUSION: Delays in patients arriving at hospital with suspected stroke can be reduced by the increased use of emergency services. Over a third of patients arrive at hospital within three hours of stroke; their management can be improved by expediting medical evaluation and performing computed tomography early.

Acute Disease↗
PubMed2002

Management of acute stroke.

Acute stroke is a medical emergency. The outcome is influenced by the rapidity and quality of initial care, which is best delivered by specialists with appropriate facilities, including 24 h access to computed tomography. Stroke management requires attention to simple details and has been summarised in clinical guidelines. General measures include control of blood glucose concentration, temperature, fluid balance, and oxygenation. Blood-pressure management is a matter for continuing research. Aspirin should be started early in ischaemic stroke, but heparin has doubtful value; antiembolism stockings may be preferable. Thrombolysis has a substantial benefit in selected circumstances, and trials continue to examine a wider role. Neuroprotection remains experimental, though magnesium is potentially of interest. Early neurosurgery has a role limited to decompression of lesions in the posterior fossa but is under trial for large hemispheric infarcts and moderate intracerebral bleeds.

Animals↗
PubMed2002

AMPA antagonist ZK200775 in patients with acute ischemic stroke: possible glial cell toxicity detected by monitoring of S-100B serum levels.

BACKGROUND AND PURPOSE: S-100B and neuron-specific enolase (NSE) serum concentrations can be used as peripheral markers of glial cell and neuronal damage, respectively. We investigated these markers in a clinical trial with the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) antagonist ZK200775 in acute ischemic stroke patients. METHODS: In a multicenter, double-blind, randomized, placebo-controlled phase 2 trial, 61 ischemic stroke patients were treated with either placebo or active drug in a dose-finding design. Twenty-five patients received placebo, 12 patients received a total dose of 262.5 mg in 48 hours (dose group 1), and 13 patients received a total dose of 525 mg in 48 hours (dose group 2). Eleven patients received a total dose of 105 mg over a period of 6 hours (dose group 3; reduction of total dose and infusion time because of adverse events in group 2). Serum concentrations of S-100B and NSE were analyzed with the use of a monoclonal sandwich immunoluminometric assay. Neurological outcome was assessed with the National Institutes of Health Stroke Scale (NIHSS). RESULTS: In group 2 there was a significant transient worsening in the mean NIHSS score 48 hours after the start of treatment. The mean increase was 11 points. This was due to reduction of consciousness (stupor and coma) in 8 of 13 patients. Neurological deterioration in group 2 was associated with a higher increase of S-100B concentrations, but not of NSE concentrations, than in the placebo group. The trial was stopped prematurely for safety reasons. CONCLUSIONS: The AMPA antagonist ZK200775 transiently worsened the neurological condition in patients with acute ischemic stroke. Our results suggest that in addition to neuronal dysfunction, glial cell toxicity may have occurred. It may be useful to introduce monitoring of serum markers of brain damage in phase 2 trials with glutamate receptor antagonists.

Acute Disease↗
PubMed2002

Turbulence and circulating cerebral emboli detectable at Doppler ultrasonography: a differentiation study in a stenotic middle cerebral artery model.

BACKGROUND AND PURPOSE: Blood flow within the middle cerebral artery can be monitored by transcranial Doppler (TCD) ultrasonography. Arterial stenosis can produce turbulent flow, but controversy remains regarding the degree of stenosis needed to cause TCD-detectable turbulence. Furthermore, cerebral emboli and turbulent flow may coexist in the same patient. The current study was designed to study the relationship between stenotic degree and TCD-detectable turbulent flow and its differentiation from cerebral emboli. METHODS: A stenotic middle cerebral artery model was constructed to allow the study of different degrees of stenosis. TCD was used to detect the turbulent flow and embolic materials in the circulation model, and signal intensities were analyzed. RESULTS: Turbulent flow was generated with a series of short, asymmetric stenoses in this test. Transition of turbulence from laminar flow began to occur at a moderate degree of stenosis (55% reduction of cross-sectional area) but became dampened at the high degrees of stenoses (>/=75%). Turbulence caused a notable increase in average Doppler signal intensity. However, the degree of stenosis was not associated with signal intensity at the region where turbulence existed, but rather was related to the mean flow velocity measured at the narrowed region. Embolic materials such as air bubbles (30 micro m) and platelet-rich clots (100 micro m) had notably higher Doppler signal intensity than that produced by turbulence. CONCLUSION: TCD-detectable turbulence predominantly developed at a moderate arterial stenosis and its acoustic signature with TCD is different from that caused by air bubbles and platelet-rich clots.

Blood Flow Velocity↗
PubMedDate not supplied

Elevated serum urate concentration independently predicts poor outcome following stroke in patients with diabetes.

BACKGROUND: Type 2 diabetes is a risk factor for stroke and confers increased risk of poor outcome and further vascular events following stroke. Hyperuricaemia occurs commonly in patients with type 2 diabetes, but its significance as a predictor of outcome following stroke is uncertain. We sought to investigate the prognostic significance of elevated serum urate concentration in diabetic subjects following stroke. METHODS: We studied a cohort of type 2 diabetes patients presenting to our unit with computed tomography-confirmed acute stroke. Fasting blood samples were drawn within 24 h of admission for urate concentration and standard battery of biochemistry and hematological tests. Information on age, stroke type, prior hypertension, smoking status, resolution time of symptoms and National Institutes of Health Stroke Score was collated. The main outcome event was time to myocardial infarction, recurrent stroke or vascular death, as defined in the CAPRIE trial. Stepwise proportional hazards regression was used to estimate the effect of the above variables on event-free survival following stroke. RESULTS: One hundred and forty patients were studied. Median follow-up duration was 974 days (IQR 163 to 1830 days). Sixty-four patients suffered an outcome event. Urate levels of greater than 0.42 mmol/L (p < 0.001) and an increasing NIHSS score (p < 0.001) independently predicted increased likelihood of suffering an event. CONCLUSION: Elevated urate concentration is significantly and independently associated with increased risk of future vascular events in diabetic stroke patients. Further studies to elucidate the mechanism of this observation are required.

Aged↗
PubMedDate not supplied

Halving effort in acute stroke trials.

The expense and substantial effort required to conduct multicenter acute stroke trials are potentially limiting factors for progress in this field. To facilitate future work, we need to expand on collaborative approaches to learn from existing trial data sets, for example, using the Virtual International Stroke Trials Archive. Using these networks, we can identify ways of reducing future effort in trials. The interaction between two or more selection criteria can be considered and can allow trials to concentrate on the most informative patients. This has the potential to shorten the recruitment period and increase power simultaneously. Through enhanced training and certification of investigators in assessing outcomes, the main outcome measures may be assessed more accurately. This also should enhance study power. The choice of outcome scale and its method of analysis can have a profound effect on trial power and likely success. The Rankin scale may have advantages over the Barthel index. By combining these various approaches, acute stroke trials can be much more efficient.

Acute Disease↗