Blood pressure and risk of stroke in patients with cerebrovascular disease. The United Kingdom Transient Ischaemic Attack Collaborative Group.
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Biomedical subjects
Publications and source records attributed to J Slattery.
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BACKGROUND: A winter excess of ischaemic stroke has been found in mortality and hospital-based studies. It is often assumed that this is due to seasonal variation in stroke incidence and several pathophysiological explanations have been proposed. We studied the incidence of stroke in relation to season and outside temperature. METHODS: The data came from a community-based study of first ever in a lifetime stroke in a defined population of about 105 000. 675 such strokes were registered over four years and the month of inset was analysed separately for cerebral infarction, primary intracerebral haemorrhage, and subarachnoid haemorrhage. FINDINGS: There was no significant seasonal variation. The incidence of primary intracerebral haemorrhage was increased at low temperatures, but there was no significant relation between the incidence of ischaemic stroke or subarachnoid haemorrhage and temperature. INTERPRETATION: The widely reported winter excess of ischaemic strokes may be an artifact due to referral bias in hospital-based studies and increased case fatality during the winter in mortality studies.
We studied the reproducibility of metabolite signals (from N-acetyl aspartate [NAA], choline, and creatine) measured with a standard single-voxel proton magnetic resonance spectroscopy technique (PRESS, TE = 135 ms, 8 ml VOI) in vitro and in two groups of normal volunteers. Spectral peak areas were quantified both by integration and by curve-fitting. In the in vitro study, the "between-days" variability (coefficient of variation [CV]) of measurements ranged from 0.9% to 2.3%. In the first group of volunteers (n = 12), single voxel spectroscopic measurements (8 ml VOI, 256 acquisitions [ACQs]) were made from mirror-image parts of the right and left hemispheres on 2 separate days. The "between-days" CV of measurements ranged from 9% to 18% for metabolite areas, and from 10% to 26% for metabolite area ratios. There were no significant differences between quantification method or hemisphere. After checking and optimising the MR scanner performance (in fact, it was virtually optimal), the second group (n = 4) each had six sequential single voxel spectroscopic measurements (each of 64 ACQs) from the right hemisphere (without moving the voxel) on each of 4 separate days. Even when the metabolites were measured from the same place in the same hemisphere sequentially six times in a 20-min period, the "within-run" CVs ranged from 4.4% to 17.2% for metabolite areas and from 9.7% to 17.0% for metabolite area ratios. The between-days CVs for the subjects ranged from 7.7% to 25.8% (metabolite areas) and from 10.1% to 22.6% (metabolite area ratios). The variability is due to a combination of random noise, subject motion, baseline artefacts in the spectra, and uncertainties in repositioning the VOIs. It is likely to represent the best reproducibility possible with 8-ml VOIs in cooperative, healthy volunteers carefully positioned on each occasion in a standard clinical scanner. Changes in metabolite levels in individuals must therefore be of the order of 20-40% before we can be reasonably confident of measuring them. Reproducibility in patients, who may be less cooperative, will probably be no better, and this must be taken into account in the interpretation of MRS studies in patients with brain pathology; for example, stroke, head injury, and tumours.
OBJECTIVE: To determine how often observer variation in the interpretation of intra-arterial angiograms might alter the decision whether or not to refer patients for carotid surgery. METHODS: A prospective study was carried out in a consecutive series of 99 patients with transient ischaemic attacks and minor strokes. Interpretable angiographic films were available for 179 carotid artery bifurcations. Stenosis of the internal carotid artery was measured using mm scales, independently by three different radiologists (A, B, and C), using the European Carotid Surgery Trial method. RESULTS: An analysis of the grouped data showed good to moderate agreement by kappa statistics for radiologists A v B, B v C, and A v C of 0.68, 0.60, and 0.70 respectively. The mean absolute difference in the estimate of stenosis by each of the different radiologists (interobserver variation) was 9.5% and for each radiologist on two separate occasions (intraobserver variation) 8.4%. The degree of observer error was smallest among severely stenosed arteries. Although the absolute differences were small, "clinically important" differences which could change the treatment recommended from surgery to no surgery (or vice versa) occurred between radiologists A and B, B and C, and A and C in: seven (3.9%), six (3.4%), and 11 (6.1%) vessels respectively. CONCLUSIONS: Because observer variation affects all of the imaging methods (Doppler, duplex, contrast arteriography, and MR angiography) used to select patients with transient ischaemic attack and stroke, these findings are likely to be widely relevant. Any centre assessing patients with cerebrovascular disease will need to implement strict quality control measures in the interpretation of angiograms (and other vascular imaging procedures) to minimise observer error and thereby reduce the number of inappropriate decisions made to refer for carotid artery surgery or not.
BACKGROUND AND PURPOSE: Carotid endarterectomy reduces the risk of carotid territory ischemic stroke ipsilateral to a recently symptomatic severe carotid stenosis. However, the benefit is limited by the risks of stroke and death associated with the operation. Although reported surgical risks vary enormously, there has been no systematic review of the published literature. METHODS: We performed a systematic review of mortality and the risk of stroke and/or death due to endarterectomy for symptomatic carotid stenosis in studies published since 1980. RESULTS: Fifty-one studies fulfilled our criteria. Overall mortality was 1.62% (95% confidence interval [CI], 1.3 to 1.9), and the risk of stroke and/or death was 5.64% (95% CI, 4.4 to 6.9). However, there was significant heterogeneity of risk of stroke and/or death (P < .001). The risk varied systematically with the methods and the authorship of the study. The risk of stroke and/or death was highest in studies in which patients were assessed by a neurologist after surgery (7.7%; 95% CI, 5.0 to 10.2) and lowest in studies with a single author affiliated with a department of surgery (2.3%; 95% CI, 1.8 to 2.7). After correcting for study methodology, there was no temporal trend in the risk of stroke and/or death between 1980 and 1995. CONCLUSIONS: The reported risks of endarterectomy for symptomatic carotid stenosis show significantly greater variability than would be expected by chance. However, much of this variability can be accounted for by differences in methodology and authorship. The 5.6% overall risk of stroke and/or death is consistent with present guidelines.
BACKGROUND AND PURPOSE: There is some evidence that carotid endarterectomy reduces the risk of ipsilateral carotid territory ischemic stroke in patients with severe asymptomatic carotid stenosis. However, the benefit of endarterectomy is dependent on a low risk of stroke and/or death due to surgery. Whether the low operative risks reported in recent clinical trials and cited in recent guidelines are widely generalizable to clinical practice is unclear. Is endarterectomy for asymptomatic carotid stenosis really safer than surgery for recently symptomatic stenosis? METHODS: We performed a systematic review comparing the risks of stroke and death due to carotid endarterectomy, performed by the same surgeons or in the same institutions, for symptomatic and asymptomatic stenosis in studies published since 1980. RESULTS: Twenty-five studies fulfilled our criteria. Mortality within 30 days of endarterectomy was 1.31% for asymptomatic stenosis and 1.81% for symptomatic stenosis (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.49 to 0.99). The risks of fatal stroke were 0.47% and 0.91%, respectively (OR, 0.57; 95% CI, 0.34 to 0.98). The overall risk of stroke and/or death was 3.35% for asymptomatic and 5.18% for symptomatic stenosis (OR, 0.61; 95% CI, 0.51 to 0.74). CONCLUSIONS: Mortality and the risk of stroke and/or death due to carotid endarterectomy are significantly lower for asymptomatic than symptomatic stenosis. These findings are consistent across virtually all studies and are likely to be widely generalizable.
The ability to measure the pH of the apoplast in situ is of special interest as a test of the cell wall acidification theory. Optical sectioning of living seedlings of corn roots using the laser scanning confocal microscope (LSCM) permits us to make pH measurements in living tissue. The pH of the apoplast of corn roots was measured by this method after infiltration with Cl-NERF, a pH-sensitive dye, along with Texas Red Dextran 3000, a pH-insensitive dye, as an internal standard. In the elongation zone of corn roots, the mean apoplastic pH was 4.9. Upon gravitropic stimulation, the pH on the convex side of actively bending roots was 4.5. The lowering of the apoplastic pH by 0.4 units appears to be sufficient to account for the increased growth on that side. This technique provides site-specific evidence for the acid growth theory of cell elongation. The LSCM permits measurements of the pH of living tissues, and has a sensitivity of approximately 0.2 pH units.
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The pharmacokinetics, safety, and efficacy in marrow transplantation of FK506-based immunosuppression for graft-versus-host disease (GVHD) prophylaxis was evaluated in an open label pilot study of 18 patients. Patients more than 12 years of age (median, 35 years; range, 15 to 50 years) with advanced hematologic malignancies receiving HLA-matched sibling marrow grafts were randomized to receive FK506 alone, FK506 and methotrexate (MTX), or FK506 and methyl-prednisolone. Of 17 evaluable patients, all had evidence of sustained marrow engraftment. The median time to an absolute neutrophil count of greater than 500/microL was 15 days for patients receiving FK506 alone or FK506 plus methylprednisolone and 23 days for FK506 plus short MTX. Pharmacokinetic studies did not show any significant difference in clearance of FK506 when administered alone or in combination with methylprednisolone or MTX. The mean bioavailability after oral administration in these same three groups was 0.49 +/- 0.1, 0.27 +/- 0.12, and 0.16 +/- 0.08, respectively (P = .003). The decrease in bioavailability may have resulted from an exacerbation of radiation-induced gastroenteritis by MTX. The most significant adverse effect associated with the administration of FK506 was nephrotoxicity, which occurred in 14 of 18 patients (78%). The mean glomerular filtration rate, determined by clearance of (99MTc)DTPA, decreased to 56% (+/- 18%) of the pretransplant baseline level by week 8 (P = .002). Eight of 18 patients (44%) developed grades II-IV acute GVHD, predominantly of the skin and gastrointestinal tract. The actuarial probability of transplant-related mortality during the first 100 days was 24%. The actuarial probability of 1-year disease-free survival was 39%. In conclusion, although bioavailability of FK506 may be affected in patients receiving MTX, this study suggests that FK506 may have a role in the management of patients after allogeneic marrow transplantation.
We aimed to determine whether the angiographic characteristics of recently symptomatic carotid stenosis predict risk of subsequent ischaemic stroke independently of the degree of stenosis. First, two observers compared the angiographic characteristics of patients who subsequently suffered a carotid distribution ischaemic stroke ipsilateral to the stenosis (n = 50) with those of stroke-free controls (n = 100) matched for the degree of stenosis of the symptomatic internal carotid artery. No significant differences were found. Secondly, seven independent observers attempted to identify the angiograms of 50 patients who subsequently suffered a stroke from those of 50 stroke-free controls matched for degree of stenosis, age and sex. None of the observers identified the stroke case more often than was expected by chance alone. We conclude that clinicians cannot differentiate between 'high risk' and 'low risk' carotid stenoses on the basis of angiographic characteristics other than the degree of stenosis.
The sensitivity of three scales of performance and handicap to the presence and development of epilepsy in patients with brain tumours was studied. Two hypothetical cases had equivalent disability, in one case due to epilepsy and in the other to physical impairment. The second case later developed epilepsy. All consultant neurologists and neurosurgeons in Scotland were asked to grade the cases using three scales commonly used for patients with cerebral glioma. Consultants rated the patient with epilepsy alone as being less disabled and handicapped than the patient with physical impairment without seizures (sign test p < 0.003). At best 21% of clinicians (p = 0.03) were able to report a change in performance score in the second case when seizures developed. These scales do not reflect changes in handicap and performance associated with tumour associated epilepsy. Clinical trial protocols for treatments for brain tumours must state how performance and handicap related to epilepsy will be measured.
From 1979 to 1985 2435 patients having had transient ischaemic attacks (TIAs) or minor ischaemic strokes, were enrolled in the UK TIA trial and were randomised to receive either aspirin 300 mg, daily or aspirin 1200 mg or placebo. Analysis of reported upper gastrointestinal bleeding events (defined as haematemesis or melaena, or both) showed a risk of bleeding in a dose dependent manner, odds ratios (95% CI) for 300 mg of aspirin = 3.3 (1.2 to 9.0) and for 1200 mg = 6.4 (2.5 to 16.5) and, as would be expected, an increased risk of hospitalisation because of bleeding also in a dose dependent manner, odds ratio = 3.6 (0.7 to 17.2) for 300 mg and 8.7 (2.0 to 37.6) for 1200 mg. Further analysis suggested greater risks of bleeding from duodenal ulcers than gastric ulcers and that bleeding is more likely early in the course of treatment with aspirin used as secondary prevention. There was also an increased risk of lower gastrointestinal bleeding, defined as fresh blood per rectum for both doses of aspirin, odds ratio 1.8 (0.5 to 6.1) for 300 mg of aspirin, and 1.5 (0.4 to 5.3) for 1200 mg of aspirin.
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The criteria for clinical response to treatment in cerebral glioma remain poorly defined, but could be made more objective if simple measures of neurological impairments were included in the definitions. We assessed the utility of simple fast previously validated tests of limb impairment (Timed nine hole peg test and 10 meter walk), memory (Williams delayed recall test) and language (Boston Aphasia Severity Rating Scale) in fifty patients with primary brain tumours to see if they could act as a surrogate for neurological impairment. The tests were compared with established measures of physical disability (Barthel Disability Index [BDI]) and handicap. Timed tests of hand function and gait were sensitive to minor impairments and were abnormal in patients with physical disability on BDI. Timed tests correlated well with handicap (rank correlation 0.734). Short term memory was impaired more commonly with tumours involving the left hemisphere (p < 0.01). Dysphasia limited testing of memory in 8%. Depression was associated with problems in limb function (p < 0.01), memory (p < 0.001), language (p < 0.001), BDI (p < 0.001) and handicap (p < 0.001). The number of abnormal fast tests also correlated with the severity of handicap (rank correlation 0.786) indicating that memory impairment and aphasia contribute to handicap and should be assessed. Median time to complete all assessments was 7 minutes 20 seconds. Utilization of these simple tests will add sensitivity and objectivity to evaluation of neurological response in clinical trials and can be performed quickly by non medical staff.
BACKGROUND AND PURPOSE: There is confusion about how carotid stenosis should be measured on angiograms. If the results of research based on different methods of measurement of stenosis are to be discussed and the results of clinical trials properly applied to routine clinical practice, measurements made by the different methods must be formally compared. METHODS: The method of measurement of stenosis used in the European Carotid Surgery Trial (ECST), that used in the North American Symptomatic Carotid Endarterectomy Trial (NASCET), and a method based on measurement of the common carotid (CC) artery lumen diameter were compared. Carotid stenosis was measured by two observers, working independently and using the three different methods of measurement, on the angiographic view of the symptomatic carotid stenosis that showed the most severe disease in 1001 patients from the ECST. RESULTS: The results of using the ECST and CC methods differed from those of using the NASCET method in the classification of stenoses as mild (0% to 29%), moderate (30% to 69%), or severe (70% to 99%) in 51% of measurements. The ECST and CC methods indicated that twice as many stenoses were severe as did the NASCET method, and classified less than a third of the number of stenoses as mild. The results of the ECST and CC methods differed from each other in 15% of measurements. The relations between measurements made by each method to those made by the others were approximately linear, so a simple equation could be derived to convert measurements made by one method to measurements made by the others. CONCLUSIONS: There were major and clinically important disparities between measurements of stenosis made using different methods of measurement on the same angiograms. However, it is possible to convert measurements made by one method to those of another using a simple arithmetic equation.
BACKGROUND AND PURPOSE: The use of three methods of measuring carotid stenosis, which produce different values on the same angiograms, has caused confusion and reduced the generalizability of the results of research. If the results of future studies are to be properly applied to clinical practice, and if noninvasive methods of imaging are to be properly validated against angiography, a single, standard method of measurement of stenosis on angiograms must be adopted. This standard method should be selected on the bases of its ability to predict risk of ipsilateral carotid distribution ischemic stroke and its reproducibility. METHODS: The method of measurement of carotid stenosis used in the European Carotid Surgery Trial (ECST), that used in the North American Symptomatic Carotid Endarterectomy Trial (NASCET), and a method based on the measurement of the common carotid (CC) lumen diameter were studied. Their use in the prediction of ipsilateral carotid distribution ischemic stroke was assessed in 1001 consecutively selected patients randomly assigned to medical treatment in the ECST. Carotid stenosis was measured by two observers working independently, using all three methods, on the angiographic view that showed the most severe stenosis of the symptomatic carotid bifurcation. Interobserver agreement was determined, and 50 angiograms were remeasured to determine intraobserver agreement. RESULTS: There was little difference in the ability of the three methods to predict ipsilateral carotid distribution ischemic stroke. The CC method was consistently the most reproducible of the three, particularly for stenosis in the clinically important range of 50% to 90%. CONCLUSIONS: The CC method of measurement should be adopted as the standard method of measuring the degree of carotid stenosis on angiograms.