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Biomedical subjects

P A Barber

Publications and source records attributed to P A Barber.

At least 19 recordsLinked to original sources
PubMed2006

Kir6.2-containing ATP-sensitive potassium channels protect cortical neurons from ischemic/anoxic injury in vitro and in vivo.

ATP-sensitive potassium (K(ATP)) channels are weak inward rectifiers that appear to play an important role in protecting neurons against ischemic damage. Cerebral stroke is a major health issue, and vulnerability to stroke damage is regional within the brain. Thus, we set out to determine whether K(ATP) channels protect cortical neurons against ischemic insults. Experiments were performed using Kir6.2(-/-) K(ATP) channel knockout and Kir6.2(+/+) wildtype mice. We compared results obtained in Kir6.2(-/-) and wildtype mice to evaluate the protective role of K(ATP) channels against focal ischemia in vivo, and, using cortical slices, against anoxic stress in vitro. Immunohistochemistry confirmed the presence of K(ATP) channels in the cortex of wildtype, but not Kir6.2(-/-), mice. Results from in vivo and in vitro experimental models indicate that Kir6.2-containing K(ATP) channels in the cortex provide protection from neuronal death. Briefly, in vivo focal ischemia (15 min) induced severe neurological deficits and large cortical infarcts in Kir6.2(-/-) mice, but not in wildtype mice. Imaging analyses of cortical slices exposed briefly to oxygen and glucose deprivation (OGD) revealed a substantial number of damaged cells (propidium iodide-labeled) in the Kir6.2(-/-) OGD group, but few degenerating neurons in the wildtype OGD group, or in the wildtype and Kir6.2(-/-) control groups. Slices from the three control groups had far more surviving cells (anti-NeuN antibody-labeled) than slices from the Kir6.2(-/-) OGD group. These findings suggest that stimulation of endogenous cortical K(ATP) channels may provide a useful strategy for limiting the damage that results from cerebral ischemic stroke.

Animals↗
PubMed2006

Ethnic differences in syringomyelia in New Zealand.

OBJECTIVE: To determine the prevalence of syringomyelia in a defined population in New Zealand and measure the prevalence of syringomyelia in the three main ethnic groups (Maori, Pacific people and Caucasians/others) living in this region. METHODS: A retrospective study of all confirmed cases of syringomyelia diagnosed in residents of northern New Zealand from 1961 to 2003. RESULTS: In all, syringomyelia was diagnosed in 137 patients. The mean age at onset of symptoms was 27.5 years and mean age at diagnosis was 32.6 years. The incidence of new cases increased from 0.76/100,000 a year between 1962 and 1971 to 4.70/100,000 a year by 1992-2001. The prevalence of syringomyelia in 2003 was 8.2/100,000 people: 5.4/100,000 in Caucasians or others, 15.4/100,000 in Maori and 18.4/100,000 in Pacific people (chi2 = 37.0, p<0.0001). Syringomyelia was more often associated with an isolated Chiari I malformation in Pacific people (84.4%) as compared with 42.9% of Maori and 38.2% of Caucasians or others (chi2 = 62.3, p<0.0001). CONCLUSION: The prevalence of syringomyelia is higher in northern New Zealand than in studies carried out before the advent of magnetic resonance imaging. The prevalence is particularly high in Maori and Pacific people. The cause of the ethnic differences in the prevalence of syringomyelia identified in this study is unexplained and warrants further investigation.

Adolescent↗
PubMed2006

Changing attitudes to the management of ischaemic stroke between 1997 and 2004: a survey of New Zealand physicians.

AIM: In 1997, a survey of New Zealand physicians' opinions on the management of stroke was carried out. Since then, there have been a number of advances in stroke therapy. We have repeated the 1997 survey to assess changes in physicians' opinions on stroke management. METHODS: A questionnaire was sent to 293 physicians responsible for patients admitted with acute stroke to hospitals throughout New Zealand. It included questions on the management of acute stroke and secondary prevention and was based on the 1997 questionnaire. RESULTS: Responses were received from 211 physicians of whom 174 (82%) managed patients with an acute stroke. The number of respondents who thought that stroke units were efficacious has increased (57% in 1997 to 89%, P < 0.001). The use of aspirin acutely (P < 0.001) and intravenous tissue plasminogen activator (P = 0.006) has also increased. In 2004, antihypertensive therapy for secondary stroke prevention would be commenced if the blood pressure was 150/90 by 98% of respondents and 140/90 by 70% of respondents. In 2004, a statin would be commenced if the total cholesterol level was 4.0 mmol/L by 56% of respondents and 5.0 mmol/L by 91% of respondents. CONCLUSIONS: This survey has shown important changes in the management of ischaemic stroke over the past 7 years.

Antihypertensive Agents↗
PubMed2006

Insular cortical ischaemia does not independently predict acute hypertension or hyperglycaemia within 3 h of onset.

OBJECTIVES: To test the hypothesis that insular cortical ischaemia is associated with acute hypertension and hyperglycaemia. METHODS: From the Canadian Activase for Stroke Effectiveness Study, which included only patients treated with thrombolysis hyperacutely (ie, within 3 h of onset of stroke), 966 patients were identified with ischaemia affecting (n = 685), or sparing (n = 281), the insular cortex. Demographic and clinical data, pretreatment indices of blood pressure, blood glucose, atrial fibrillation, and clinical imaging and outcome measures were compared between the two groups. Multivariable linear regression was used to assess predictors of systolic blood pressure and glucose levels before thrombolysis. RESULTS: Pretreatment hypertension (p = 0.009), but not hyperglycaemia (p = 0.32), was predicted by insular ischaemia in univariable linear regression analyses. After adjusting for other factors, however, insular cortical ischaemia was not found to be an independent predictor for acute hypertension or hyperglycaemia. CONCLUSIONS: Raised blood pressure or serum glucose levels in hyperacute (<3 h) cerebral ischaemia is not independently predicted by insular involvement. Several hours are required for sympathetic manifestations of insular ischaemia to evolve.

Acute Disease↗
PubMed2005

Imaging of the brain in acute ischaemic stroke: comparison of computed tomography and magnetic resonance diffusion-weighted imaging.

BACKGROUND AND OBJECTIVES: Controversy exists about the optimal imaging technique in acute stroke. It was hypothesised that CT is comparable with DWI, when both are read systematically using quantitative scoring. METHODS: Ischaemic stroke patients who had CT within six hours and DWI within seven hours of onset were included. Five readers used a quantitative scoring system (ASPECTS) to read the baseline (b) and follow up CT and DWI. Use of MRI in acute stroke was also assessed in patients treated with tissue plasminogen activator (tPA) by prospectively recording reasons for exclusion. Patients were followed clinically at three months. RESULTS: bDWI and bCT were available for 100 consecutive patients (admission median NIHSS = 9). The mean bDWI and bCT ASPECTS were positively related (p<0.001). The level of interrater agreement ranged from good to excellent across all modalities and time periods. Bland-Altman plots showed more variability between bCT and bDWI than at 24 hours. The difference between bCT and bDWI was < or =2 ASPECTS points. Of bCT scans with ASPECTS 8-10, 81% had DWI ASPECTS 8-10. Patients with bCT ASPECTS of 8-10 were 1.9 times more likely to have a favourable outcome at 90 days than those with a score of 0-7 (95% CI 1.1 to 3.1, p = 0.002). The relative likelihood of favourable outcome with a bDWI ASPECTS 8-10 was 1.4 (95% CI 1.0 to 1.9, p = 0.10). Of patients receiving tPA 45% had contraindications to urgent MRI. CONCLUSION: The differences between CT and DWI in visualising early infarction are small when using ASPECTS. CT is faster and more accessible than MRI, and therefore is the better neuroimaging modality for the treatment of acute stroke.

Aged↗
PubMed2005

Refining the perfusion-diffusion mismatch hypothesis.

BACKGROUND AND PURPOSE: The Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) tests the hypothesis that perfusion-weighted imaging (PWI)-diffusion-weighted imaging (DWI) mismatch predicts the response to thrombolysis. There is no accepted standardized definition of PWI-DWI mismatch. We compared common mismatch definitions in the initial 40 EPITHET patients. METHODS: Raw perfusion images were used to generate maps of time to peak (TTP), mean transit time (MTT), time to peak of the impulse response (Tmax) and first moment transit time (FMT). DWI, apparent diffusion coefficient (ADC), and PWI volumes were measured with planimetric and thresholding techniques. Correlations between mismatch volume (PWIvol-DWIvol) and DWI expansion (T2(Day 90-vol)-DWI(Acute-vol)) were also assessed. RESULTS: Mean age was 68+/-11, time to MRI 4.5+/-0.7 hours, and median National Institutes of Health Stroke Scale (NIHSS) score 11 (range 4 to 23). Tmax and MTT hypoperfusion volumes were significantly lower than those calculated with TTP and FMT maps (P<0.001). Mismatch > or =20% was observed in 89% (Tmax) to 92% (TTP/FMT/MTT) of patients. Application of a +4s (relative to the contralateral hemisphere) PWI threshold reduced the frequency of positive mismatch volumes (TTP 73%/FMT 68%/Tmax 54%/MTT 43%). Mismatch was not significantly different when assessed with ADC maps. Mismatch volume, calculated with all parameters and thresholds, was not significantly correlated with DWI expansion. In contrast, reperfusion was correlated inversely with infarct growth (R=-0.51; P=0.009). CONCLUSIONS: Deconvolution and application of PWI thresholds provide more conservative estimates of tissue at risk and decrease the frequency of mismatch accordingly. The precise definition may not be critical; however, because reperfusion alters tissue fate irrespective of mismatch.

Aged↗
PubMed2005

Intra-arterial thrombolysis for retinal artery occlusion: the Calgary experience.

INTRODUCTION: Retinal artery occlusion represents a medical emergency with poor prognosis for visual recovery. Spontaneous improvement is estimated to occur in less than 15% of central retinal artery occlusion (CRAO) cases and conventional treatments have provided only limited benefit. Intra-arterial thrombolysis has been reported as a potentially efficacious and safe treatment. METHODS: We performed a retrospective chart review of all retinal artery occlusion cases treated with intra-arterial recombinant tissue-type plasminogen activator (rtPA) from January 1998 to May 2004. Patients received Goldmann perimetry visual field testing at a variable interval following the procedure (2 days-2.5 years). Visual acuity (VA) was re-assessed in May 2004. RESULTS: Eight cases (59-77 years) were treated for CRAO, 6-18 hours post-onset with intra-arterial rtPA (10-20 mg over 15-60 minutes); one case of branch occlusion (BRAO) was treated with 30 mg rtPA over 75 minutes, 12 hours post-onset. Among the six patients with CRAO assessed in clinic, three experienced improvement in VA by two or more gradations (Snellen lines); three improved by one gradation. However, none achieved a final VA better than 20/300. The case of branch occlusion improved to a VA of 20/20. All patients had residual monocular field defects. CONCLUSIONS: Our findings reveal a limited benefit for intra-arterial tPA compared to the rate of spontaneous improvement and conventional forms of therapy for retinal artery occlusion.

Adult↗
PubMed2004

The probability of middle cerebral artery MRA flow signal abnormality with quantified CT ischaemic change: targets for future therapeutic studies.

OBJECTIVES: In this study we define the probability of vascular abnormality in the middle cerebral artery (MCA) territory according to the extent of ischaemic change seen using computed tomography (CT). We assessed the sensitivity and specificity of the hyperdense middle cerebral artery (HMCA) and the "dot" sign using magnetic resonance angiography (MRA). METHODS: Patients presenting with ischaemic stroke had a CT scan (<6 h) prior to MRI (<7 h). A quantitative CT scoring system (ASPECTS) was applied to CT and diffusion weighted images (DWI) at baseline and follow up (24 h) by five independent observers. The presence of HMCA and the MCA "dot" sign was also evaluated. An expert reader assessed the 3D time of flight (TOF) MRA in the anterior circulation for areas of decreased vascular signal in the MCA territory, with an absent signal taken to represent severely reduced or absent flow. RESULTS: A total of 100 consecutive patients had baseline CT and MR scans. The median NIHSS was 9. The median CT ASPECTS was 8 and equalled the median DWI ASPECTS. There were a total of 10 HMCA and 19 MCA "dot" signs, with four patients having both HMCA and "dot" signs. A total of 47 MRA flow signal abnormalities were observed in the anterior circulation. CONCLUSIONS: In the absence of accessible neurovascular imaging, the extent of CT ischaemia (ASPECTS) is a strong predictor of vascular occlusion. The CT hyperdense artery signs have a high positive predictive value but low negative predictive value.

Aged↗
PubMed2004

The rise and fall of NMDA antagonists for ischemic stroke.

It has long been accepted that high concentrations of glutamate can destroy neurons, and this is the basis of the theory of excitotoxicity during brain injury such as stroke. Glutamate N-methyl-D-aspartate (NMDA) receptor antagonists such as Selfotel, Aptiganel, Gavestinel and others failed to show neuroprotective efficacy in human clinical trials or produced intolerable central nervous system adverse effects. The failure of these agents has been attributed to poor studies in animal models and to poorly designed clinical trials. We also speculate that NMDA receptor antagonism may have hindered endogenous mechanisms for neuronal survival and neuroregeneration. It remains to be proven in human stroke whether NMDA receptor antagonism can be neuroprotective.

Animals↗
PubMed2003

Hemi-orolingual angioedema and ACE inhibition after alteplase treatment of stroke.

One hundred seventy-six consecutive patients treated with IV tissue plasminogen activator (tPA) for acute ischemic stroke were examined prospectively, and orolingual angioedema was found in nine (5.1%; 95% CI 2.3 to 9.5). The reaction was typically mild, transient, and contralateral to the ischemic hemisphere. Risk of angioedema was associated with angiotensin-converting enzyme inhibitors (relative risk [RR] 13.6; 95% CI 3.0 to 62.7) and signs on initial CT of ischemia in the insular and frontal cortex (RR 9.1; 95% CI 1.4 to 30.0).

Aged↗
PubMed2001

Symptomatic hemorrhage after alteplase therapy not due to silent ischemia.

BACKGROUND: Stroke thrombolysis-related intracerebral hemorrhage may occur remotely from the anatomical site of ischemia. One postulated mechanism for this is simultaneous multiple embolization with hemorrhage into a "silent" area of ischemia. RESULTS: A patient suffered a disabling stroke affecting the right cerebral hemisphere. He was treated with intravenous alteplase and underwent extensive early imaging with multimodal MRI. Several hours after treatment he developed a brainstem hemorrhage despite having no evidence of ischemia on DWI MRI in the brainstem. CONCLUSION: Not all occurrences of remote ICH after stroke thrombolysis are secondary to multiple emboli with silent ischemia.

Aged↗
PubMed2001

A three-item scale for the early prediction of stroke recovery.

BACKGROUND: Accurate assessment of prognosis in the first hours of stroke is desirable for best patient management. We aimed to assess whether the extent of ischaemic brain injury on magnetic reasonance diffusion-weighted imaging (MR DWI) could provide additional prognostic information to clinical factors. METHODS: In a three-phase study we studied 66 patients from a North American teaching hospital who had: MR DWI within 36 h of stroke onset; the National Institutes of Health Stroke Scale (NIHSS) score measured at the time of scanning; and the Barthel Index measured no later than 3 months after stroke. We used logistic regression to derive a predictive model for good recovery. This logistic regression model was applied to an independent series of 63 patients from an Australian teaching hospital, and we then developed a three-item scale for the early prediction of stroke recovery. FINDINGS: Combined measurements of the NIHSS score (p=0.01), time in hours from stroke onset to MR DWI (p=0.02), and the volume of ischaemic brain tissue on MR DWI (p=0.04) gave the best prediction of stroke recovery. The model was externally validated on the Australian sample with 0.77 sensitivity and 0.88 specificity. Three likelihood levels for stroke recovery-low (0-2), medium (3-4), and high (5-7)-were identified on the three-item scale. INTERPRETATION: The combination of clinical and MR DWI factors provided better prediction of stroke recovery than any factor alone, shortly after admission to hospital. This information was incorporated into a three-item scale for clinical use.

Activities of Daily Living↗
PubMed2001

Why are stroke patients excluded from TPA therapy? An analysis of patient eligibility.

BACKGROUND: Thrombolytic therapy for acute stroke (<3 hours) will not have a major impact on death and dependency unless it is accessible to more patients. OBJECTIVE: To determine why patients with ischemic stroke did not receive IV TPA and assess the availability of this therapy to patients with ischemic stroke. METHODS: Consecutive patients with acute ischemic stroke were prospectively identified at a university teaching hospital between October 1996 and December 1999. Additional patients with ischemic stroke were identified that were admitted to one of three other hospitals in the Calgary region during the study period. The Oxford Community Stroke Programme Classification was used to record type and side of stroke. RESULTS: Of 2165 stroke patients presenting to the university hospital, 1168 (53.9%) were diagnosed with ischemic stroke, 31.8% with intracranial hemorrhage (intracerebral, subarachnoid, or subdural), and 13.9% with TIA. Delay in presentation to emergency department beyond 3 hours excluded 73.1% (854/1168). Major reasons for delay included uncertain time of onset (24.2%), patients waited to see if symptoms would improve (29%), delay caused by transfer from an outlying hospital (8.9%), and inaccessibility of treating hospital (5.7%). Twenty-seven percent of patients with ischemic stroke (314/1168) were admitted within 3 hours of sympton onset and of these 84 (26.7%) patients received IV TPA. The major reasons for exclusion in this group of patients (<3 hours) were mild stroke (13.1%), clinical improvement (18.2%), perceived protocol exclusions (13.6%), emergency department referral delay (8.9%), and significant comorbidity (8.3%). Of those patients who were considered too mild or were documented to have had significant improvement, 32% either remained dependent at hospital discharge or died during hospital admission. Throughout the region there was a total of 1806 ischemic stroke patients (admitted to all four Calgary hospitals). During this study period, 4.7% received IV TPA. CONCLUSIONS: The majority of patients are unable to receive TPA for acute ischemic stroke because they do no not reach the hospital soon enough. Of those patients presenting within 3 hours, 27% received the therapy but a further 31% were excluded because their symptoms were either considered too mild or were rapidly improving. Subsequently, a third of these patients were left either dependent or dead, bringing into question the initial decision not to treat.

Aged↗
PubMed2001

Prediction of the final infarct volume within 6 h of stroke using single photon emission computed tomography with technetium-99m hexamethylpropylene amine oxime.

BACKGROUND: A simple method to predict the final infarct volume within 6 h of onset of hemispheric ischemic stroke based on the measurement of cerebral blood flow (CBF) using single photon emission computed tomography (SPECT) with techneticum-99m hexamethylpropylene amine oxime ((99m)Tc-HMPAO) was investigated in a clinical model involving patients without definite early reperfusion or clinical recovery. METHODS: A group of 16 patients (group 1) was used to establish the methodology, which was then validated in a second group of 14 patients (group 2). The final infarct volume was defined using computed tomography (CT) performed at least 7 days after stroke. The relative CBF threshold value, expressed as a percentage of the mean contralateral hemispheric value, which most closely estimated the final infarct size on coregistered CT was established for each patient. RESULTS: The mean threshold CBF value for group 1 was 63.7%. When this value was used to predict infarct size in group 2, a close correlation was observed between the actual and the estimated sizes (r = 0.973, p < 0.0001). This value was not time dependent. CONCLUSIONS: If no significant early reperfusion or clinical recovery occurs, a CBF threshold value of 63.7% on (99m)Tc-HMPAO SPECT performed within 6 h of stroke onset will reliably predict the final infarct size.

Aged↗
PubMed2001

Comparison of MRI perfusion imaging and single photon emission computed tomography in chronic stroke.

There have been few direct comparisons between MR perfusion-weighted imaging (PWI) and established perfusion imaging techniques, and none in chronic stroke. We therefore studied 17 chronic hemispheric infarction patients (mean, 90 days) and compared hypoperfusion volumes determined from PWI maps of relative cerebral blood flow (rCBF) and volume (rCBV), and mean transit time (rMTT) with those measured with (99)Tc-HMPAO single photon emission computed tomography (SPECT). Comparisons were also made between infarct size (T(2)-WI) and clinical scales. Correlations were found between lesion location and volume in all three PWI hemodynamic parameter maps with clinical state and lesions on SPECT and T(2)-WI. In 3 patients, rCBF and rCBV lesions extended well beyond the borders of moderate-sized infarctions. We conclude that in chronic stroke, PWI can delineate regions of abnormal perfusion that reflect the degree of functional impairment and structural damage. The finding of peri-infarct hypoperfusion suggests that PWI may have the potential to provide a rapid and non-invasive template against which interventional strategies aimed at promoting functional recovery may be investigated.

Aged↗
PubMed2001

Hyperdense sylvian fissure MCA "dot" sign: A CT marker of acute ischemia.

BACKGROUND AND PURPOSE: The hyperdense appearance of the main middle cerebral artery (HMCA) is now a familiar early warning of large cerebral infarction, brain edema, and poor prognosis. This article describes the hyperdensity associated with embolic occlusion of branches of the middle cerebral artery in the sylvian fissure (MCA "dot" sign). We define it and determine its incidence, diagnostic value, and reliability. METHODS: CT scans performed on patients with acute ischemic stroke within 3 hours of symptom onset were analyzed for signs of thromboembolic stroke and evidence of early CT ischemia. Two neuroradiologists and 2 stroke neurologists initially blinded to all clinical information and then with knowledge of the affected hemisphere evaluated scans for the presence of the MCA dot sign, the HMCA sign, and early MCA territory ischemic changes. RESULTS: Of 100 consecutive patients who presented within 3 hours of symptom onset, 91 were considered at symptom onset to have anterior circulation stroke syndromes. Early CT ischemia was seen in 74% of these baseline CT scans. The HMCA sign was seen in 5% of CT scans, whereas the MCA dot sign was seen in 16%. All patients then received intravenous tissue plasminogen activator. All 5 patients with an HMCA sign, including 2 with an associated MCA dot sign, were either dead or dependent at 3 months. The 14 patients with an MCA dot sign alone were independent at 3 months in 64% of cases, compared with 50% without the sign (Fisher's exact test P:=0.79). Balanced kappa statistics for both the HMCA and the MCA dot sign were in the moderate to good range when the stroke symptom side was given. CONCLUSIONS: The MCA dot sign is an early marker of thromboembolic occlusion of the distal MCA branches seen in the sylvian fissure and is associated with better outcome than the HMCA sign.

Acute Disease↗