PubMed Health⌕ Search

Biomedical subjects

J Wardlaw

Publications and source records attributed to J Wardlaw.

At least 19 recordsLinked to original sources
PubMed2006

Magnetic resonance perfusion diffusion mismatch and thrombolysis in acute ischaemic stroke: a systematic review of the evidence to date.

BACKGROUND: The mismatch between perfusion and diffusion lesions on magnetic resonance perfusion-weighted imaging (PWI)/diffusion-weighted imaging (DWI) may help identify patients for thrombolysis. Evidence underlying this hypothesis was assessed. METHODS: All papers describing magnetic resonance PWI/DWI findings in patients with acute ischaemic stroke, and their functional and/or radiological outcome at 1 month, with or without thrombolysis were systematically reviewed. RESULTS: 11 papers fulfilled the inclusion criteria. Among these, there were 5 different mismatch definitions and at least 7 different PWI methods. Only 3 papers including 61 patients with and 18 without mismatch provided data on mismatch, outcome and influence of thrombolysis. Mismatch (v no mismatch) without thrombolysis was associated with a non-significant twofold increase in the odds of infarct expansion (odds ratio (OR) 2.2, 95% confidence interval (CI) 0.34 to 14.1), which did not change with thrombolysis (OR 2.0, 95% CI 0.37 to 10.9). Half of the patients without mismatch also had infarct growth (with or without thrombolysis). No data were available on functional outcome. CONCLUSIONS: Standardised definitions of mismatch and perfusion are needed. Infarct growth may occur even in the absence of mismatch. Currently, data available on mismatch are too limited to guide thrombolysis in routine practice. More data are needed from studies including patients with and without mismatch, and randomised treatment allocation, to determine the role of mismatch.

Diffusion Magnetic Resonance Imaging↗
PubMed2004

Thrombolysis (different doses, routes of administration and agents) for acute ischaemic stroke.

BACKGROUND: Thrombolytic therapy is effective for acute myocardial infarction, a disease with some similarities to acute ischaemic stroke. Meta-analyses suggest a net benefit in acute ischaemic stroke. OBJECTIVES: To assess different thrombolytic agents, and different regimens, in acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (last searched to June 2003), MEDLINE (1966 to July 2003) and EMBASE (1980 to July 2003). We handsearched four Japanese journals, contacted researchers and pharmaceutical companies, and attended relevant conferences. SELECTION CRITERIA: Randomised and quasi-randomised trials of different doses of a thrombolytic agent, or different agents, or the same agent given by different routes, in people with confirmed acute ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility and quality, and extracted the data. MAIN RESULTS: Ten trials involving 1641 patients, 8 conducted in Japan, 1 in China and 1 in the USA, were included. Concealment of allocation was poorly described. Different doses (of tissue plasminogen activator or urokinase) were compared in seven trials (n = 1072 patients). Different agents (tissue plasminogen activator versus urokinase; tissue-cultured urokinase versus conventional urokinase) were compared in three trials (n = 688 patients). One trial compared different routes of administration (intravenous plus intraarterial tissue plasminogen activator versus intraarterial tissue plasminogen activator alone, n = 35 patients). As some trials compared different agents and different doses, some patients contributed to two analyses. A higher dose of thrombolytic therapy was associated with a three-fold increase in fatal intracranial haemorrhages (Odds ratio (OR) 3.25, 95% confidence interval (CI) 1.32 to 7.97) compared with a lower dose of the same agent (based on 16 events among 539 higher-dose patients and 4 events among 533 lower-dose patients in 7 trials). There was no statistically significant difference in early (OR 1.01, 95% CI 0.58 to 1.74) or late (OR 0.94, 95% CI 0.58 to 1.53) deaths between lower and higher doses. Data were inadequate to assess the effect of dose on functional outcome. No statistically significant difference was shown between different thrombolytic agents tested. The data from the pilot trial comparing different routes of administration were inconclusive. REVIEWERS' CONCLUSIONS: These scant data suggest that higher doses of thrombolytic agents may lead to higher rates of bleeding. However, the evidence is inadequate to conclude whether lower doses of thrombolytic agents are more effective than higher doses, or whether one agent is better than another, or which route of administration is the best, in acute ischaemic stroke.

Brain Ischemia↗
PubMed2004

Low myo-inositol and high glutamine levels in brain are associated with neuropsychological deterioration after induced hyperammonemia.

The neuropsychological effect of hyperammonemia is variable. This study tests the hypothesis that the effect of ammonia on the neuropsychological function in patients with cirrhosis is determined by the ability of the brain to buffer ammonia-induced increase in glutamine within the astrocyte by losing osmolytes like myo-inositol (mI) and not by the magnitude of the induced hyperammonemia. Fourteen cirrhotic patients with no evidence of overt hepatic encephalopathy were given a 75-g amino acid (aa) solution mimicking the hemoglobin molecule to induce hyperammonemia. Measurement of a battery of neuropsychological function tests including immediate memory, ammonia, aa, and short-echo time proton magnetic resonance spectroscopy were performed before and 4 h after administration of the aa solution. Eight patients showed deterioration in the Immediate Memory Test at 4 h. Demographic factors, severity of liver disease, change in plasma ammonia, and aa profiles after the aa solution were similar in those that showed a deterioration compared with those who did not. In patients who showed deterioration in the memory test, the mI-to-creatine ratio (mI/Cr) was significantly lower at baseline than those that did not deteriorate. In contrast, the glutamate/glutamine-to-Cr ratio was significantly greater in the patients that deteriorated. The observation that deterioration in the memory test scores was greater in those with lower mI/Cr supports the hypothesis that the neuropsychological effects of induced hyperammonemia is determined by the capacity of the brain to handle ammonia-induced increase in glutamine.

Adult↗
PubMed2003

Increased blood-brain barrier permeability in type II diabetes demonstrated by gadolinium magnetic resonance imaging.

OBJECTIVES: Patients with type II diabetes are at increased risk of cognitive impairment. The retinal and renal complications of diabetes follow microvascular damage permitting small arterioles to leak, hence the cerebral damage might also follow loss of blood-brain barrier (BBB) integrity. Magnetic resonance (MR) brain imaging with intravenous gadolinium (Gd) diethylenetriamine pentaacetic acid (Gd-DTPA) was used to identify increased BBB permeability. METHODS: Ten well controlled type II diabetic patients aged 65-70 years and 10 controls underwent MR brain imaging with fluid attenuated inversion recovery (FLAIR); T1 weighted (T1W) volumetric imaging before; and T1W volumetric imaging at 5, 15, 30, 45, 60, and 90 minutes after intravenous Gd-DTPA. The T1W image before Gd-DTPA was subtracted from the images at each time point after Gd-DTPA. Net signal intensity was plotted against time for different brain regions. White matter hyperintensities were scored from the FLAIR image. RESULTS: The signal intensity/time curves showed that brain signal intensity increased more in the diabetic group than controls during the first 15 minutes after Gd-DTPA, particularly in the basal ganglia (p=0.018). Signal intensity in controls peaked at five minutes and diabetics at 15 minutes. Subjects with more white matter hyperintensities had greater signal increase after Gd-DTPA, whether diabetic or not (p=0.001). CONCLUSIONS: Increased BBB permeability with MR imaging was detected in patients with type II diabetes or white matter hyperintensities. Increased permeability of the BBB might account for some of the cerebral effects of type II diabetes, and so possibly also for the effect of other conditions that affect the microvasculature (like hypertension), on the brain.

Aged↗
PubMed2002

Repeatability of long and short echo-time in vivo proton chemical-shift imaging.

We carried out long (145 ms) and short (25 ms) echo time spectroscopic imaging of the brain (chemical-shift imaging, CSI) on two occasions 1 week apart on 15 healthy individuals. We found coefficients of variation (CVs) generally in the range 10-25% for long and 15-30% for short echo-time measurements. The CVs of metabolite ratios were higher by about 5-10%. Limits of agreement (defined as mean+/-2 SD of the week 1-week 2 differences) were wider at the shorter echo time. The modest repeatability may be due in part to the difficulty of repositioning spectroscopic voxels at a scale of 1 mm. The generally higher CVs and wider limits of agreement at TE25 ms suggest that the increased spectral complexity more than offsets the theoretical advantage of increased signal at short echo-times. Analysis of variance general linear modelling of metabolites and metabolite ratios showed that, in general, the subject, region of the brain and hemisphere were more important than the occasion in explaining the variability of results. Unless information on short-T2 metabolites is specifically required, better results can probably be achieved with longer echo-times. The magnitude of the CVs needs to be taken into account in the calculation of sample size for cross-sectional or linear studies.

Adult↗
PubMed2002

Magnetic resonance brain imaging in people with dizziness: a comparison with non-dizzy people.

BACKGROUND: Dizziness is a common symptom affecting about 30% of people over the age of 65. OBJECTIVE: To investigate the hypothesis that structural abnormalities of the brain and cervical cord are more common in dizzy than in non-dizzy subjects. METHODS: A case-control study of subjects over the age of 65 with and without dizziness: 125 dizzy subjects and 86 non-dizzy subjects were recruited from the community through articles in the local press. Magnetic resonance imaging (MRI) of the brain and neck was performed, and was read by a consultant neuroradiologist blind to the clinical details. RESULTS: All dizzy subjects and all controls had at least one structural abnormality. Cerebral atrophy was found in 86% of dizzy subjects and 85% controls (p = 1.0) At least one white matter lesion was found in 69% of dizzy subjects and 78% controls (p = 0.21). White matter lesions in the midbrain were more common in dizzy than in non-dizzy subjects (22% v 4%, p < 0.001). There were no significant differences in the prevalence of cord compression, cervical subluxation, facet joint degeneration, vertebral artery compression, or vertebral artery occlusion between dizzy and non-dizzy subjects. CONCLUSIONS: Structural abnormalities of the brain and neck are common in both dizzy and non-dizzy subjects. "Routine" MRI is unlikely to reveal a specific cause for dizziness. The observation of more frequent white matter lesions in the midbrain in dizzy subjects requires further study to determine whether small vessel changes could cause dizziness in older people.

Aged↗
PubMed2000

Fibrinogen depleting agents for acute ischaemic stroke.

BACKGROUND: Fibrinogen depleting agents reduce fibrinogen in blood plasma, reduce blood viscosity and hence increase blood flow. This may help remove the blood clot blocking the artery and re-establish blood flow to the affected area of the brain after an ischaemic stroke. The risk of haemorrhage may be less than with thrombolytic agents. OBJECTIVES: The objective of this review was to assess the effect of fibrinogen depleting agents in people with acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register, Embase (to January 1996) and the Index of scientific and technical proceedings (1982 to 1996). We handsearched 10 Chinese journals and the proceedings of the 4th Chinese Stroke Conference (1995). We contacted Chinese and Japanese researchers, and drug companies. SELECTION CRITERIA: Randomised and quasi-randomised trials of fibrinogen depleting agents started within 14 days of stroke onset, compared with control in patients with definite or possible ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion criteria, assessed trial quality and extracted the data. MAIN RESULTS: Three trials involving 182 patients were included. All trials tested ancrod. Allocation concealment was adequate in two trials. Fibrinolytic therapy appeared to reduce the number of deaths during the scheduled treatment period (odds ratio 0.33, 95% confidence interval 0.13 to 0.85). There was no difference in death from all causes at the end of follow-up (odds ratio 0.57, 95% confidence interval 0.27 to 1.23). The risk of haemorrhage appeared to be small, but there were too few data to be conclusive. One trial in 132 people showed a statistically non-significant decrease in the odds of being dead or disabled at the end of follow-up (odds ratio 0.52, 95% confidence interval 0.26 to 1.03). REVIEWER'S CONCLUSIONS: Although ancrod appears to be promising, it is not possible to draw reliable conclusions from the available data.

Ancrod↗
PubMed2000

Thrombolysis (different doses, routes of administration and agents) for acute ischaemic stroke.

BACKGROUND: Thrombolytic therapy is effective for acute myocardial infarction, a vascular disease with some similarities to acute ischaemic stroke. OBJECTIVES: The objective of this review was to assess the effect of different thrombolytic agents, and different regimens in acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register and Embase (1980 to 1997). We handsearched Japanese and Chinese journals. We contacted researchers in the field and pharmaceutical companies. SELECTION CRITERIA: Randomised and quasi-randomised trials of different doses of a thrombolytic agent, or one thrombolytic agent compared with another, or the same agent given by different routes, in people with confirmed acute ischaemic stroke. Trials were included if treatment was started within 14 days of stroke onset. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed eligibility, trial quality and extracted the data. MAIN RESULTS: Eight trials involving 1334 people were included. Concealment of allocation was generally adequate. All the trials were conducted in Japan. Different doses (of tissue plasminogen activator or urokinase) were compared in seven trials. Different agents (tissue plasminogen activator versus urokinase, or tissue-cultured urokinase versus conventional urokinase) were compared in three trials. Few data were available for functional outcomes. A higher dose of thrombolytic therapy was associated with a five-fold increase in fatal intracranial haemorrhages (odds ratio 5.02, 95% confidence interval 1.56 to 16. 18). This was based on 11 events among 369 higher-dose patients and one event among 356 lower-dose patients in six trials. There was a non-significant trend towards more early deaths or clinically significant intracranial haemorrhages. No difference in late deaths or extra-cranial haemorrhages was shown between low and higher doses. However, very few of these events occurred. No difference was shown between the different thrombolytic agents tested. REVIEWER'S CONCLUSIONS: There is not enough evidence to conclude whether lower doses of thrombolytic agents might be safer or more effective than higher doses in acute ischaemic stroke. It is not possible to conclude whether one agent might be better than another, or which route of administration might be best. No comparative data for streptokinase have been found.

Brain Ischemia↗
PubMed2000

What pathological components indicate carotid atheroma activity and can these be identified reliably using ultrasound?

OBJECTIVE: The aim of this project was to determine whether histological features of 'active' plaque as described in the coronary circulation following acute myocardial infarction were similar in the carotid circulation, and whether these factors could be detected ultrasonically. METHOD: Endarterectomy specimens were prospectively collected, and examined histologically and assessed by two observers for ulceration, inflammation, size of necrotic core, thickness of fibrous cap, haemorrhage and luminal thrombosis. Ultrasound of the plaque obtained preoperatively was similarly coded (blind to pathology) and compared with the pathology. RESULTS: In 42 endarterectomy specimens, there was a highly significant relationship between a thin fibrous cap and a large necrotic core (P<0.002), irregular plaque contour (P<0.05) and ulceration (P<0.01) and between a large necrotic core (P<0.002) and ulceration and inflammation (P<0.05). Increasing amounts of necrosis were associated with more surface thrombosis (P<0.02). Ultrasound detected the thickness of the fibrous cap and 'any necrosis or haemorrhage' with some reliability (kappas are 0.53 and 0.5, respectively), but not ulceration, necrosis or haemorrhage on their own. CONCLUSION: Features corresponding to active atheromatous plaque are similar in the carotid and coronary arteries, and some of these, namely lucent areas in the plaque (corresponding to necrosis or haemorrhage) and the thickness of the fibrous cap, can be determined reliably with ultrasound.

Arteriosclerosis↗
PubMed2000

Critical appraisal of the design and reporting of studies of imaging and measurement of carotid stenosis.

BACKGROUND AND PURPOSE: Several hundred studies have been published over the last few years on imaging and measurement of carotid stenosis. Despite all this research, there is still no consensus about how best to image and measure stenosis. One possible explanation for this is that many of the studies have not been large enough or methodologically sound enough to allow useful conclusions to be drawn. We aimed to assess the design and methods of a random sample of published studies of imaging and measurement of carotid stenosis using 9 simple criteria. METHODS: A formal literature search was performed for studies of imaging and measurement of carotid stenosis. Two subsets were randomly selected for detailed assessment: 20 studies published before 1991 and 20 published between 1993 and 1997 (some years after the initial publication of the ECST and NASCET trials). The criteria used to assess the selected studies were as follows: prospective rather than retrospective study design; patient selection based on a consecutive series or a random sample; adequate detail of study population; adequate detail of imaging techniques; inclusion of all investigations, ie, patients with poor-quality imaging were not excluded; blinded assessment of images; adequate detail of derivation of measurement of stenosis from images or data; adequate data on the reproducibility of measurements of stenosis; and study powered according to a sample-size calculation. RESULTS: There were many basic methodological deficiencies in both subsets of studies, with relatively little evidence of improvement with time. For example, only 33% of studies were prospective, only 45% studied a consecutive or random selection of patients, and only 38% reported any data on the reproducibility of measurements. More than half of the studies satisfied < or =4 of the 9 quality criteria. However, there was considerable variation between studies, with 7 studies satisfying > or = 7 criteria and 10 studies satisfying < or =2. No study was based on a sample-size calculation. The number of patients studied was often small, particularly in the more recent studies: median sample size was 100 in the 1970-1990 studies and 58 in the 1993-1997 studies (P<0.0001). CONCLUSIONS: The design and reporting of published studies of imaging and measurement of carotid stenosis are poor and have not improved much in recent years. The majority of published studies are not of a sufficient standard to enable the results to be used to inform clinical practice. The utility of future studies could be improved considerably by better adherence to 9 simple methodological guidelines.

Carotid Stenosis↗
PubMed1999

Delays in stroke referrals.

Assessment of acute stroke by hospital physicians will have to speed up if we are to expect referral to hospital and computed tomography (both previously targets of criticism) to improve.

Acute Disease↗
PubMed1999

Research funding.

Explore the source record for details and available documents.

Biomedical Research↗
PubMed1999

Atherosclerotic plaque at the carotid bifurcation: CT angiographic appearance with histopathologic correlation.

BACKGROUND AND PURPOSE: The likelihood that carotid plaque will give rise to cerebral ischemia probably relates to the degree of arterial stenosis and to plaque morphology. The aim of this study was to assess whether features seen at CT angiography might be used to predict carotid plaque stability by comparing CT angiograms with histopathologic examinations of the carotid artery bifurcation. METHODS: Nine patients with symptomatic severe carotid stenosis at intraarterial angiography had CT angiography of the carotid bifurcation before carotid endarterectomy. After endarterectomy, multiple sections of the specimens through the carotid bifurcation were examined histologically. Plaque characteristics recorded included the proportion of necrotic/lipid core, presence of hemorrhage, extent of fibrosis, ulceration, calcification, inflammatory cell infiltrate, and fibrous cap thickness. Corresponding CT angiograms were assessed for plaque size, distribution, and radiodensity as well as presence of calcific density and ulceration. Histologic findings and CT angiograms were compared. RESULTS: Plaque with a large necrotic/lipid core, which was often hemorrhagic, was found in 16 of 23 sections, and in 15 of these this histologic appearance corresponded with patchy or homogeneous low density on CT angiograms. Six of seven predominantly fibrous plaques were of soft-tissue density on CT angiograms. High density consistent with calcification was seen more frequently on CT angiograms than it was detected histologically, but CT angiography depicted plaque ulceration poorly (four ulcers at histology; two false-positive and two false-negative findings at CT angiography). CONCLUSION: CT angiography is a promising method for assessing the lumen and wall of the carotid artery. The apparent correlation between histologic appearance and plaque density on CT angiograms has important implications for the prediction of plaque stability, even though ulceration is shown inconsistently.

Arteriosclerosis↗
PubMed1999

Dsyembryoplastic neuroepithelial tumour with discrete bilateral multifocality: further evidence for a germinal origin.

We report the case of a middle aged woman who developed refractory complex partial seizures in her early twenties. She had a right coloboma and neurological examination was normal. Neuropsychological assessments revealed mild impairments of non-verbal memory, and visuospatial and constructional difficulties. Serial CT and MRI showed multiple nodular abnormalities in her mid-brain, diencephalon, subependymal region and both mesial temporal lobes. EEG recording revealed a right medial temporal focus. She underwent en bloc temporal lobectomy. The surgical pathology revealed mesial temporal dysembryoplastic neuroepithelial tumour (DNET) in association with extensive, contiguous neocortical dysplasia. The proliferation marker MIB-1 revealed up to 2% labelling in tumour areas resembling conventional oligodendroglioma. In the two years since surgery she has been seizure free and the remaining MR brain abnormalities have not changed. The very unusual centripetal MRI pattern of discrete multifocal lesions with the characteristic T1 and T2 features of DNET would support the dysembyroplastic germinal origin that was proposed by Daumas-Duport et al. (1988) in their original description of the lesion. The neuroradiological, neuropathological and clinical features of this case are compared with the two previous cases of multifocal DNET.

Adult↗
PubMed1998

A flow model of cerebral aneurysms for use with power Doppler studies.

It has recently been observed using power Doppler that cerebral aneurysms appear to change size through the cardiac cycle. The purpose of this study was to develop a pulsatile flow model of cerebral aneurysm expansion and to investigate whether the observations of pulsation could be confirmed using the model. The model consisted of a latex bubble glued onto the side of a latex tube. A computer controlled pump was used to generate pulsatile flow. The degree of bubble expansion was adjusted by the use of flow restrictor placed in the downstream section of the flow rig. Ultrasound images were acquired using an Acuson 128 XP/10V colour flow scanner. True expansion (maximum area/minimum area) was measured from the B-scan image using a 7 MHz probe. Three observers measured expansion of the simulated aneurysm from the power Doppler images using a 2 MHz probe. Expansion measured with the power Doppler decreased as the colour gain setting increased, and decreased as the persistence increased. The true expansion of 1.43 was comparable with the colour gain set optimally for a persistence value of 3. The model allows simple investigations of the relationship between true aneurysm expansion and that measured from the power Doppler images. Colour gain and persistence settings must be standardized in clinical studies.

Humans↗