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Biomedical subjects

L Wechsler

Publications and source records attributed to L Wechsler.

At least 19 recordsLinked to original sources

Pretreatment ipsilateral regional cortical blood flow influences vessel recanalization in intra-arterial thrombolysis for MCA occlusion.

BACKGROUND AND PURPOSE: The aim of acute stroke interventions is to achieve recanalization of the target occluded artery. We sought to determine whether pretreatment cortical cerebral blood flow (CBF) was associated with vessel recanalization in patients undergoing intra-arterial therapy. METHODS: This is a retrospective analysis of patients who underwent a quantitative xenon CT blood flow study and were noted to have a documented M1 middle cerebral artery (MCA) or carotid terminus occlusion less than 6 hours from symptom onset between January 1997 and April 2001. Twenty-three patients who underwent intra-arterial thrombolysis were included in the analysis. Univariate and multivariate analyses were performed to determine whether pretherapy CBF was correlated to the likelihood of recanalization. RESULTS: A total of 23 patients were studied in this analysis with a median age of 69 (range 32-81) and median National Institutes of Health Stroke Score of 19 (range, 8-22). Twelve patients (52%) underwent combined intravenous/intra-arterial therapy, and 11 patients (48%) were treated with intra-arterial thrombolytics alone. Successful vessel recanalization (Thrombolysis in Myocardial Infarction classification 2 or 3 flow) occurred in 13 patients (57%). The only variable associated with recanalization in multivariate modeling was mean ipsilateral MCA CBF (odds ratio, 1.25; 95% confidence interval, 1.01-1.54; P = .035). A receiver operating characteristic curve was generated, and a mean ipsilateral MCA CBF threshold of 18 mL/100 g/min was found to be the threshold for successful recanalization. CONCLUSIONS: Our study suggests that patients with higher mean ipsilateral MCA CBF are more likely to recanalize. The threshold for successful revascularization may be 18 mL/100 g/min. Further study is required to determine whether pretreatment CBF is related to recanalization success.

Adult↗

Clinical importance of microbleeds in patients receiving IV thrombolysis.

BACKGROUND: Cerebral microbleeds (MBs) detected on gradient echo (GRE) imaging may be a risk factor for hemorrhagic complications in patients with stroke treated with IV tissue plasminogen activator (tPA). METHODS: The authors prospectively evaluated patients with acute ischemic stroke treated with IV tPA between 3 and 6 hours of symptom onset. MRI scans, including GRE imaging, were performed prior to tPA treatment, 3 to 6 hours after treatment and at day 30. The authors compared the frequency of hemorrhagic complications after thrombolysis in patients with and without MBs on their baseline GRE imaging. RESULTS: Seventy consecutive patients (mean age, 71 +/- 29 years; 31 men, 39 women) were included. MBs were identified in 11 patients (15.7%) on baseline GRE imaging. There was no significant difference in the frequency of either symptomatic or asymptomatic hemorrhagic complications after thrombolysis between patients with and without MBs at baseline. None of the 11 patients with MBs (0%) at baseline had a symptomatic intracerebral hemorrhage compared with 7 of 59 patients who did not have baseline MBs (11.9%). In addition, no patients with baseline MBs had asymptomatic hemorrhagic transformation observed at the site of any pre-treatment MB. CONCLUSIONS: The presence of cerebral microbleeds on gradient echo imaging does not appear to substantially increase the risk of either symptomatic or asymptomatic brain hemorrhage following IV tissue plasminogen activator administered between 3 and 6 hours after stroke onset.

Adult↗

Changes in cognitive function after neuronal cell transplantation for basal ganglia stroke.

Reported is the change in cognitive function after neuronal cell transplantation as a treatment for basal ganglia stroke. Nine subjects (two controls, seven transplants), all over 2 years post stroke, completed a comprehensive neuropsychological test battery prior to and 6 months after treatment. Four transplanted subjects who had strokes in the nondominant hemisphere showed marked improvement on the Rey Complex Figure, a test of visuospatial/constructional ability and nonverbal memory.

Aged↗

Clomethiazole Acute Stroke Study in ischemic stroke (CLASS-I): final results.

BACKGROUND AND PURPOSE: A previous trial (the Clomethiazole Acute Stroke Study) generated the hypothesis that clomethiazole is effective in patients with a major ischemic stroke (total anterior circulation syndrome), and this was tested in the present study. METHODS: A total of 1198 patients with major ischemic stroke and a combination of limb weakness, higher cortical dysfunction, and visual field deficits were randomly assigned to clomethiazole (68 mg/kg IV over 24 hours) or placebo. The study drug was initiated within 12 hours of symptom onset. Functional outcome and neurological recovery were assessed at days 7, 30, and 90, with the proportion of patients with a Barthel Index > or =60 at last follow-up as the primary outcome measure. RESULTS: The patients were randomly assigned equally, and the two treatment groups were well matched for baseline characteristics, including stroke severity (mean National Institutes of Health Stroke Scale score 16.9+/-5.2). Ninety-six percent were classified as total anterior circulation syndrome. The proportion of patients reaching a Barthel Index score of > or =60 was 42% in the clomethiazole-treated group and 46% in the placebo-treated group (odds ratio, 0.81; 95% CI, 0.62 to 1.05; P=0.11). There was no evidence of efficacy on any secondary outcome variables (modified Rankin Score, National Institutes of Health Stroke Scale, Scandinavian Stroke Scale, and 30-day CT infarct volumes) compared with placebo. Subgroup analysis showed a similar lack of treatment effect in patients treated early (<6 hours) and in those treated later (6 to 12 hours). Somnolence was an expected pharmacological effect of clomethiazole, and this occurred during treatment as an adverse event in half of the patients randomly assigned to study drug. CONCLUSIONS: The target population was selected, and sufficient drug was given to produce the expected pharmacological effect in the brain. Clomethiazole does not improve outcome in patients with major ischemic stroke.

Acute Disease↗

Serial [18F] fluorodeoxyglucose positron emission tomography after human neuronal implantation for stroke.

OBJECTIVE: There is no known effective treatment for chronic stroke. In this report, we used positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) to map the metabolic brain response to neuronal cell implantation in the first human neuroimplantation trial for stroke. METHODS: Twelve patients (nine men, three women; mean age +/- standard deviation, 60.8+/-8.3 yr) with chronic basal ganglia infarction and persistent motor deficit underwent FDG PET within 1 week before and 6 and 12 months after stereotactic implantation of human neuronal cells. Serial neurological evaluations during a 52-week postoperative period included the National Institutes of Health stroke scale and the European stroke scale. RESULTS: Alterations in glucose metabolic activity in the stroke and surrounding tissue at 6 and 12 months after implantation correlated positively with motor performance measures. CONCLUSION: FDG PET performed as part of an initial open-label human trial of implanted LBS-Neurons (Layton BioScience, Sunnyvale, CA) for chronic stroke demonstrates a relationship between relative regional metabolic changes and clinical performance measures. These preliminary findings suggest improved local cellular function or engraftment of implanted cells in some patients.

Aged↗

Transplantation of cultured human neuronal cells for patients with stroke.

Transplantation of cultured neuronal cells is safe in animal models and improves motor and cognitive deficits in rats with stroke. The authors studied the safety and feasibility of human neuronal cellular transplantation in patients with basal ganglia stroke and fixed motor deficits, including 12 patients (aged 44 to 75 years) with an infarct 6 months to 6 years previously (stable for at least 2 months). Serial evaluations (12 to 18 months) showed no adverse cell-related serologic or imaging-defined effects. The total European Stroke Scale score improved in six patients (3 to 10 points), with a mean improvement 2.9 points in all patients (p = 0. 046). Six of 11 PET scans at 6 months showed improved fluorodeoxyglucose uptake at the implant site. Neuronal transplantation is feasible in patients with motor infarction.

Adult↗

Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism.

CONTEXT: Intravenous tissue-type plasminogen activator can be beneficial to some patients when given within 3 hours of stroke onset, but many patients present later after stroke onset and alternative treatments are needed. OBJECTIVE: To determine the clinical efficacy and safety of intra-arterial (IA) recombinant prourokinase (r-proUK) in patients with acute stroke of less than 6 hours' duration caused by middle cerebral artery (MCA) occlusion. DESIGN: PROACT II (Prolyse in Acute Cerebral Thromboembolism II), a randomized, controlled, multicenter, open-label clinical trial with blinded follow-up conducted between February 1996 and August 1998. SETTING: Fifty-four centers in the United States and Canada. PATIENTS: A total of 180 patients with acute ischemic stroke of less than 6 hours' duration caused by angiographically proven occlusion of the MCA and without hemorrhage or major early infarction signs on computed tomographic scan. INTERVENTION: Patients were randomized to receive 9 mg of IA r-proUK plus heparin (n = 121) or heparin only (n = 59). MAIN OUTCOME MEASURES: The primary outcome, analyzed by intention-to-treat, was based on the proportion of patients with slight or no neurological disability at 90 days as defined by a modified Rankin score of 2 or less. Secondary outcomes included MCA recanalization, the frequency of intracranial hemorrhage with neurological deterioration, and mortality. RESULTS: For the primary analysis, 40% of r-proUK patients and 25% of control patients had a modified Rankin score of 2 or less (P = .04). Mortality was 25% for the r-proUK group and 27% for the control group. The recanalization rate was 66% for the r-proUK group and 18% for the control group (P<.001). Intracranial hemorrhage with neurological deterioration within 24 hours occurred in 10% of r-proUK patients and 2% of control patients (P = .06). CONCLUSION: Despite an increased frequency of early symptomatic intracranial hemorrhage, treatment with IA r-proUK within 6 hours of the onset of acute ischemic stroke caused by MCA occlusion significantly improved clinical outcome at 90 days.

Aged↗

Depictions of the kidney through the ages.

Recent publications [American Journal of Nephrology (1985-1995)] have contributed much to our understanding of the history of nephrology. Whether the earliest medical knowledge of the kidney was kindled in Egypt, by the Hindus in India, in ancient China, or by Assyro-Babylonians we cannot determine with certainty. What is known is that the invention of the printing press (circa 1450 AD), with the subsequent availability of translations of earlier writings plus new text editions, contributed in prodigious measure to the development of the critical and questioning character of medicine. The availability of different book illustration techniques also contributed to the development of medical knowledge. We have examined major descriptions of the kidney in 16th-, 17th- and 18th-century original works, all held by the Becker Medical Library, Washington University. The accuracy of illustrations of the observed kidney was highly variable, but each description has its place in book and 'kidney' history.

Anatomy, Artistic↗

Lung cancer in chromate-exposed aerospace workers.

A retrospective cohort study evaluated the risk of lung cancer in aerospace workers with minimum of 6 months' employment in jobs with chromium [VI] exposure (n = 2429). Standardized incidence ratios (SIR) estimated the risk of lung cancer by duration of employment in chromate-exposure jobs and cumulative exposure based on industrial hygiene and work-history data. The overall SIR for lung cancer was 0.8 (observed [Obs] = 15). Lung cancer risk was inversely related to estimates of cumulative chromate exposure and duration of employment as a painter. Although based on few cases, an elevated lung cancer risk was found in subjects who had worked for 5 or more years as a chrome plater or surface processor tank tender (Obs = 2, SIR = 1.9) and sander/masker or polisher (Obs = 3, SIR = 2.7). A clear association was not observed between chromate exposure and the risk of lung cancer in this population of workers.

Adult↗

Recent developments in transcranial Doppler sonography.

Transcranial Doppler mapping, dual monitoring, color imaging, emboli detection, and insonation after administration of contrast media are recent technological advances that promise to bring new capabilities to transcranial Doppler ultrasonography, and are likely to change its applications in the near future. This article presents a critical review of these developments.

Cerebrovascular Disorders↗

CT after intracranial intraarterial thrombolysis for acute stroke.

PURPOSE: To determine the incidence, appearance, and clinical significance of lesions mimicking intraparenchymal hemorrhages on CT in patients treated with intracranial intraarterial thrombolysis for acute strokes. METHODS: Ten cases of acute stroke treated with direct intraarterial urokinase infusion were retrospectively reviewed. Clinical and radiographic findings before and after therapy were all evaluated. RESULTS: Six (60%) of the 10 patients showed areas of increased attenuation on CT shortly after thrombolytic therapy. The lesions were associated with clinical deterioration in two cases (20%); in these two cases the lesions persisted on CT for several days. The lesions were asymptomatic in two (20%) cases; the lesions cleared on CT within 24 hours in those two patients. In two (20%) patients, immediate clinical improvement was evident despite the radiodense areas. These lesions also cleared within 24 hours. CT Hounsfield unit measurements of four of the lesions revealed very high Hounsfield units in two lesions, only one of which was a symptomatic lesion. MR in two cases revealed residue of hemorrhage. CONCLUSION: Intraparenchymal areas of increased attenuation may be seen on the CT scans of patients after intraarterial thrombolysis. The density is often at least partially attributable to contrast extravasation. The lesions should not necessarily be interpreted as hemorrhage alone, especially in the absence of clinical deterioration. Rapid clearing may be a positive prognostic sign.

Acute Disease↗

Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke.

An open angiography-based, dose rate escalation study on the effect of intravenous infusion of recombinant tissue plasminogen activator (rt-PA) on cerebral arterial recanalization in patients with acute focal cerebral ischemia was performed at 16 centers. Arterial occlusions consistent with acute ischemia in the carotid or vertebrobasilar territory in the absence of detectable intracerebral hemorrhage were prerequisites for treatment. After the 60-minute rt-PA infusion, arterial perfusion was assessed by repeat angiography and computed tomography scans were performed at 24 hours to assess hemorrhagic transformation. Of 139 patients with symptoms of focal ischemia, 80.6% (112) had complete occlusion of the primary vessel at a mean of 5.4 +/- 1.7 hours after symptom onset. No dose rate response of cerebral arterial recanalization was observed in 93 patients who completed the rt-PA infusion. Middle cerebral artery division (M2) and branch (M3) occlusions were more likely to undergo recanalization by 60 minutes than were internal carotid artery occlusions. Hemorrhagic infarction occurred in 20.2% and parenchymatous hematoma in 10.6% of patients over all dose rates, while neurological worsening accompanied hemorrhagic transformation (hemorrhagic infarction and parenchymatous hematoma) in 9.6% of patients. All findings were within prospective safety guidelines. No dose rate correlation with hemorrhagic infarction, parenchymatous hematoma, or both was seen. Hemorrhagic transformation occurred significantly more frequently in patients receiving treatment at least 6 hours after symptom onset. No relationship between hemorrhagic transformation and recanalization was observed. This study indicates that site of occlusion, time to recanalization, and time to treatment are important variables in acute stroke intervention with this agent.

Acute Disease↗

Correlative angiographic and pathologic findings in the diagnosis of ulcerated plaques in the carotid artery.

We determined the accuracy of angiography in the diagnosis of internal carotid ulcers by comparing the angiographic reports with the pathologic findings in 36 endarterectomy specimens. Eighteen of these specimens had microscopic ulcerations, and the observer with the highest accuracy rate read 12, of which ten were ulcerated. These results revealed a sensitivity of 56%, a specificity of 89%, and an overall accuracy of 61% for angiography. The ulcers were classified into types A, B, and C to assess the interobserver agreement rate among three readers. This resulted in a 4% interobserver agreement among a total of 75 ulcers. Because of the high interobserver disagreement and the poor correlation between angiographic and pathologic findings in the surgical specimens, we conclude that the diagnosis of carotid artery ulceration by angiography is not reliable.

Angiography↗

Transcranial Doppler in brain death.

Transcranial Doppler examinations (TCD) of 24 brain-dead adult patients demonstrated persistent movement of blood within the middle cerebral arteries in 21. The characteristic pattern of Doppler shift frequencies, seen in 14, was a sharply contoured, brief anterograde systolic envelope with reversed diastolic flow. Five others had variants of this pattern, and two had anterograde flow throughout the cardiac cycle, except at the end of diastole. This suggests that the internal carotid and proximal middle cerebral artery circulation remains patent, but distal resistance to flow in the brain is very high in the majority of brain-dead patients. Three other patients with absent brainstem reflexes but persistent EEG activity had normal TCD patterns. The characteristic pattern on TCD may be a useful ancillary finding in the diagnosis of brain death, and normal TCD patterns probably exclude the diagnosis.

Brain↗

Swallowing syncope: observations in the absence of conduction system or esophageal disease.

A patient is described with the clinical syndrome of "swallowing syncope" who reproducibly demonstrated sinus bradycardia, A-H prolongation, and intranodal atrioventricular block in response to swallowing during electrophysiologic study. Baseline electrophysiologic and esophageal manometric results were normal, as was his response to other vagal maneuvers. Demand ventricular pacing alleviated his symptoms. These findings suggest that "swallowing syncope" is mediated via an esophageocardiac reflex and can occur in the absence of cardiac conduction system or esophageal disease.

Bradycardia↗

Quantitation of regional cerebral glucose metabolism.

Kinetic analysis of 18F-labeled 2-fluoro-2-deoxy-D-glucose (2FDG) has been carried out in 28 studies on 25 subjects. The object of the analysis was to determine the practical problems of quantitation of glucose metabolic rate (GMR) using the Sokoloff model with 2FDG. We found that arterial and venous plasma concentration of 2FDG yielded equivalent values of the integrated plasma concentration (IPC*) and that one arterial or venous plasma sample at 30 min serves to predict IPC* to within +/- 7%. These observations suggest that quantitation is indeed possible in such subjects without using complex arterial or venous sampling procedures. The average values of K1, K2, and K3 are observed to be 0.14 +/- 0.08, 0.20 +/- 0.10, and 0.030 +/- 0.012 min-1. The data are consistent with a value of lumped constant of 0.4 and a considerable spread in global values of GMR (30%) in an unselected group of subjects.

Blood Glucose↗