Search PubMed⌕ Search

Biomedical subjects

A J Furlan

Publications and source records attributed to A J Furlan.

At least 19 recordsLinked to original sources
PubMed2001

Cerebral hemorrhage after intra-arterial thrombolysis for ischemic stroke: the PROACT II trial.

OBJECTIVE: To analyze the frequency, clinical characteristics, and predictors of symptomatic intracerebral hemorrhage (ICH) after intraarterial (IA) thrombolysis with recombinant pro-urokinase (r-proUK) in acute ischemic stroke. METHOD: The authors conducted an exploratory analysis of symptomatic ICH from a randomized, controlled clinical trial of IA thrombolysis with r-proUK for patients with angiographically documented occlusion of the middle cerebral artery within 6 hours from stroke onset. Patients (n = 180) were randomized in a ratio of 2:1 to either 9 mg IA r-proUK over 120 minutes plus IV fixed-dose heparin or IV fixed-dose heparin alone. As opposed to intention to treat, this analysis was based on "treatment received" and includes 110 patients given r-proUK and 64 who did not receive any thrombolytic agent. The remaining six patients received out-of-protocol urokinase and were excluded from analysis. The authors analyzed centrally adjudicated ICH with associated neurologic deterioration (increase in NIH Stroke Scale [NIHSS] score of > or =4 points) within 36 hours of treatment initiation. RESULTS: Symptomatic ICH occurred in 12 of 110 patients (10.9%) treated with r-proUK and in two of 64 (3.1%) receiving heparin alone. ICH symptoms in r-proUK-treated patients occurred at a mean of 10.2 +/- 7.4 hours after the start of treatment. Mortality after symptomatic ICH was 83% (10/12 patients). Only blood glucose was significantly associated with symptomatic ICH in r-proUK-treated patients based on univariate analyses of 24 variables: patients with baseline glucose >200 mg/dL experienced a 36% risk of symptomatic ICH compared with 9% for those with < or =200 mg/dL (p = 0.022; relative risk, 4.2; 95% CI, 1.04 to 11.7). CONCLUSIONS: Symptomatic ICH after IA thrombolysis with r-proUK for acute ischemic stroke occurs early after treatment and has high mortality. The risk of symptomatic ICH may be increased in patients with a blood glucose >200 mg/dL at stroke onset.

Acute Disease↗
PubMed2001

Community use of intravenous tissue plasminogen activator for acute stroke: results of the brain matters stroke management survey.

BACKGROUND AND PURPOSE: Little is known of neurologists' viewpoints regarding intravenous tPA use or institutional readiness to evaluate potential thrombolytic candidates. METHODS: Surveys were distributed at the Brain Matters Stroke Management Workshops held in 16 cities in the United States. RESULTS: Intravenous tPA was administered by 46.9% of responding neurologists. Almost 30% (29.9%) of surveyed neurologists were "very convinced" of its efficacy, whereas 61.6% were "very concerned" about the risk of intracranial hemorrhage. Only half of the respondents believed their institutions could meet all NINDS-recommended stroke-evaluation time targets. CONCLUSIONS: Neurologists' enthusiasm for the efficacy of intravenous tPA is tempered by their concern about intracranial hemorrhage. Institutional readiness for evaluating acute stroke patients is not optimized.

Acute Disease↗
PubMed2001

Cooling for acute ischemic brain damage (cool aid): an open pilot study of induced hypothermia in acute ischemic stroke.

BACKGROUND AND PURPOSE: Hypothermia is effective in improving outcome in experimental models of brain infarction. We studied the feasibility and safety of hypothermia in patients with acute ischemic stroke treated with thrombolysis. METHODS: An open study design was used. All patients presented with major ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score >15) within 6 hours of onset. After informed consent, patients with a persistent NIHSS score of >8 were treated with hypothermia to 32+/-1 degrees C for 12 to 72 hours depending on vessel patency. All patients were monitored in the neurocritical care unit for complications. A modified Rankin Scale was measured at 90 days and compared with concurrent controls. RESULTS: Ten patients with a mean age of 71.1+/-14.3 years and an NIHSS score of 19.8+/-3.3 were treated with hypothermia. Nine patients served as concurrent controls. The mean time from symptom onset to thrombolysis was 3.1+/-1.4 hours and from symptom onset to initiation of hypothermia was 6.2+/-1.3 hours. The mean duration of hypothermia was 47.4+/-20.4 hours. Target temperature was achieved in 3.5+/-1.5 hours. Noncritical complications in hypothermia patients included bradycardia (n=5), ventricular ectopy (n=3), hypotension (n=3), melena (n=2), fever after rewarming (n=3), and infections (n=4). Four patients with chronic atrial fibrillation developed rapid ventricular rate, which was noncritical in 2 and critical in 2 patients. Three patients had myocardial infarctions without sequelae. There were 3 deaths in patients undergoing hypothermia. The mean modified Rankin Scale score at 3 months in hypothermia patients was 3.1+/-2.3. CONCLUSION: Induced hypothermia appears feasible and safe in patients with acute ischemic stroke even after thrombolysis. Refinements of the cooling process, optimal target temperature, duration of therapy, and, most important, clinical efficacy, require further study.

Acute Disease↗
PubMed2000

Use of tissue-type plasminogen activator for acute ischemic stroke: the Cleveland area experience.

CONTEXT: Little is known regarding outcomes after intravenous tissue-type plasminogen activator (IV tPA) therapy for acute ischemic stroke outside a trial setting. OBJECTIVE: To assess the rate of IV tPA use, the incidence of symptomatic intracerebral hemorrhage (ICH), and in-hospital patient outcomes throughout a large urban community. DESIGN: Historical prospective cohort study conducted from July 1997 through June 1998. SETTING: Twenty-nine hospitals in the Cleveland, Ohio, metropolitan area. PATIENTS: A total of 3948 patients admitted to a study hospital with a primary diagnosis of ischemic stroke (International Classification of Diseases, Ninth Revision, Clinical Modification code 434 or 436). MAIN OUTCOME MEASURES: Rate of IV tPA use and occurrence of symptomatic ICH among patients treated with tPA; proportion of patients receiving tPA whose treatment deviated from national guidelines; in-hospital mortality among patients receiving tPA compared with that among ischemic stroke patients not receiving tPA and with mortality predicted by a model. RESULTS: Seventy patients (1.8%) admitted with ischemic stroke received IV tPA. Of those, 11 patients (15.7%; 95% confidence interval [CI], 8.1%-26.4%) had a symptomatic ICH (of which 6 were fatal) and 50% (95% CI, 37.8%-62.2%) had deviations from national treatment guidelines. In-hospital mortality was significantly higher among patients treated with tPA (15.7%) compared with patients not receiving tPA (5.1%, P<.001) and compared with the model's prediction (7.9%; P<.006). CONCLUSIONS: A small proportion of patients admitted with acute ischemic stroke in Cleveland received tPA; they experienced a high rate of ICH. Cleveland community experience with tPA for acute ischemic stroke may differ from that reported in clinical trials.

Aged↗
PubMed2000

Intra-arterial thrombolysis in acute stroke.

A relatively small number of studies were published on the intra-arterial therapy of stroke in the past year. Those reports, however, do offer strong evidence for the feasibility and safety of this therapeutic approach. Partly on the basis of these data it has become evident that the intra-arterial thrombolytic therapy of acute ischemic stroke is at least as effective as intravenous thrombolysis. There remain, however, many unresolved issues before such therapy can become a part of the standard of care.

Acute Disease↗
PubMed2000

Brain tissue sodium is a ticking clock telling time after arterial occlusion in rat focal cerebral ischemia.

BACKGROUND AND PURPOSE: Many patients with acute stroke are excluded from receiving thrombolysis agents within the necessary time limit (3 or 6 hours from stroke onset) because they or their family members are unable provide the time of stroke onset. Brain tissue sodium concentration ([Na(+)]) increases gradually and incessantly during the initial hours of experimental focal cerebral ischemia but only in severely damaged brain regions. We propose that this steady increase in [Na(+)] can be used to estimate the time after arterial occlusion in the rat middle cerebral artery occlusion model of ischemic stroke. METHODS: Sixteen anesthetized Sprague-Dawley rats underwent permanent middle cerebral artery occlusion combined with bilateral common artery occlusion. After 100 to 450 minutes, diffusion-weighted MRI was used to generate apparent diffusion coefficient (ADC) maps, cerebral blood flow (CBF) was determined with (14)C-iodoantipyrine (in a subset of 7 animals), and the brain was frozen. Autoradiographic CBF sections and punch samples for Na(+) analysis were obtained from the brain at the same level of the MR image. Severely at risk regions were identified with an ADC of <520 microm(2)/s and, in the subset, with both ADC of <520 microm(2)/s and CBF of <40 mL. 100 g(-1). min(-1). RESULTS: Both CBF and the ADC dropped quickly and remained stable in the initial hours after ischemic onset. Linear regression revealed strong linearity between [Na(+)] and time after onset, with a slope of 0.95 or 1.00 (mEq/kg DW)/min, with both ADC and ADC-plus-CBF criteria, respectively. The 95% CIs at 180 and 360 minutes were between 41 and 52 minutes. CONCLUSIONS: The time after ischemic onset can be estimated with this 2-step process. First, ADC and CBF are used to identify severely endangered regions. Second, the [Na(+)] in these regions is used to estimate time after onset. The favorable 95% CIs at the time limits for thrombolytic therapy and the availability of measurements of ADC, CBF, and [Na(+)] in humans through the use of MRI suggest that this time-estimation scheme could be used to assess the appropriateness of thrombolysis for patients who do not know when the stroke occurred.

Animals↗
PubMed2000

Stent-assisted angioplasty of intracranial vertebrobasilar atherosclerosis: an initial experience.

OBJECT: Patients with intracranial vertebrobasilar artery (VBA) atherosclerotic occlusive disease have few therapeutic options. Unfortunately, VBA transient ischemic attacks (TIAs) herald a lethal or devastating event within 5 years in 25 to 30% of patients. The authors report their initial experience with eight patients in whom medically refractory TIAs secondary to intracranial posterior circulation atherosclerotic occlusive lesions were treated with stent-assisted angioplasty. METHODS: Eight patients (six men), ranging in age from 43 to 77 years, experienced signs and symptoms of VBA insufficiency despite combination therapy with warfarin and antiplatelet agents. Angiographic studies revealed severe distal vertebral (four patients), proximal basilar (one patient), or proximal and midbasilar stenoses (three patients). Aspirin and clopidogrel were administered for 3 days before primary angioplasty and stent placement, and this regimen was maintained by the patients on discharge. Patients underwent heparinization during the procedure and were given a bolus and 12-hour infusion of abciximab. A neurologist specializing in stroke evaluated all patients before and after the procedure. The VBAs in all patients were successfully revascularized with 7 to 28% residual stenosis. Six patients experienced no neurological complications. One patient died the evening of the procedure due to a massive subarachnoid hemorrhage. Two patients had groin hematomas, one developed congestive heart failure, and one had transient encephalopathy. All surviving patients are asymptomatic up to 8 months postoperatively. CONCLUSIONS: Although primary intracranial VBA angioplasty with stent insertion is technically feasible, complications associated with the procedure can be life threatening. As experience is gained with this procedure, it may be offered routinely as an alternative therapy to patients with medically refractory posterior circulation occlusive disease that may develop into catastrophic VBA insufficiency.

Abciximab↗
PubMed1999

Intra-arterial thrombolysis for perioperative stroke after open heart surgery.

Recent major surgery is an exclusion criterion for thrombolysis. Six patients with acute ischemic stroke underwent intra-arterial thrombolysis after recent open heart surgery without clinically significant bleeding complications, although one patient developed a small, asymptomatic cerebellar hemorrhage. Intra-arterial thrombolysis may be an option for patients with cerebral embolism in the perioperative period.

Aged↗
PubMed1999

Cortical NOS inhibition raises the lower limit of cerebral blood flow-arterial pressure autoregulation.

The maintenance of constant cerebral blood flow (CBF) as arterial blood pressure is reduced, commonly referred to as CBF-pressure autoregulation, is typically characterized by a plateau until the vasodilatory capacity is exhausted at the lower limit, after which flow falls linearly with pressure. We investigated the effect of cortical, as opposed to systemic, nitric oxide synthase (NOS) inhibition on the lower limit of CBF-pressure autoregulation. Forty-four Sprague-Dawley rats were anesthetized with halothane and N2O in O2. With a closed cranial window placed the previous day in a ventilated and physiologically stable preparation, we determined the CBF using laser-Doppler flowmetry. Animals with low reactivity to inhaled CO2 and suffused ADP or ACh were excluded. Five arterial pressures from 100 to 40 mmHg were obtained with controlled hemorrhagic hypotension under cortical suffusion with artificial cerebrospinal fluid (aCSF) and then again after suffusion for 35 (n = 5) and 105 min (n = 10) with aCSF, 10(-3) M Nomega-nitro-L-arginine (L-NNA; n = 12), or 10(-3) M Nomega-nitro-D-arginine (D-NNA; n = 5). An additional group (n = 7) was studied after a 105-min suffusion of L-NNA followed by a single blood withdrawal procedure. The lower limit of autoregulation was identified visually by four blinded reviewers as a change in the slope of the five-point plot of CBF vs. mean arterial blood pressure. The lower limit of 90 +/- 4.3 mmHg after 105 min of 1 mM L-NNA suffusion was increased compared with the value in the time-control group of 75 +/- 5.3 mmHg (P < 0.01; ANOVA) and the initial value of 67 +/- 3.7 mmHg (P < 0.001). The lower limit of 84 +/- 5.9 mmHg in seven animals with 105 min of suffusion of 1 mM L-NNA without previous blood withdrawal was significantly increased (P < 0.01) in comparison with 70 +/- 1.9 mmHg from those with just aCSF suffusion (n = 37). No changes in lower limit for the other agents or conditions, including 105 or 35 min of aCSF or 35 min of L-NNA suffusion, were detected. The lack of effect on the lower limit with D-NNA suffusion suggests an enzymatic mechanism, and the lengthy L-NNA exposure of 105 min, but not 35 min, suggests inhibition of a diffusionally distant NOS source that mediates autoregulation. Thus cortical suffusion of L-NNA raises the lower limit of autoregulation, strongly suggesting that nitric oxide is at least one of the vasodilators active during hypotension as arterial pressure is reduced from normal.

Animals↗
PubMed1999

Acute ischemic stroke: new strategies for management and prevention. Interview by Wayne Kuznar.

Emergency thrombolysis in acute ischemic stroke now relies on the delivery of IV t-PA within 3 hours of stroke onset. Among the 20% of stroke patients who reach the hospital within that 3-hour window, few ultimately receive t-PA. The convergence of new imaging techniques and investigational intra-arterial therapy offers the potential to increase the number of successfully treated cases and improve functional outcomes. Stepped-up awareness campaigns can help reduce the time between stroke onset and hospitalization. Antiplatelet agents are showing promise for prevention of stroke. For patients at high risk, carotid endarterectomy and stenting may significantly reduce the likelihood of stroke occurrence.

Acute Disease↗
PubMed1998

PROACT: a phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke. PROACT Investigators. Prolyse in Acute Cerebral Thromboembolism.

BACKGROUND AND PURPOSE: To test the safety and recanalization efficacy of intra-arterial local delivery of plasminogen activators in acute ischemic stroke, a randomized trial of recombinant pro-urokinase (rpro-UK) versus placebo was undertaken in patients with angiographically documented proximal middle cerebral artery occlusion. METHODS: After exclusion of intracranial hemorrhage by CT scan, patients with abrupt onset of symptoms of focal ischemia likely to receive treatment within 6 hours who satisfied all clinical eligibility criteria underwent carotid angiography. Patients displaying Thrombolysis in Acute Myocardial Infarction grade 0 or 1 occlusion of the M1 or M2 middle cerebral artery were randomized 2:1 to receive rpro-UK (6 mg) or placebo over 120 minutes into the proximal thrombus face. All patients received intravenous heparin. Recanalization efficacy was assessed at the end of the 2-hour infusion, and intracerebral hemorrhage causing neurological deterioration was assessed at 24 hours. RESULTS: Of 105 patients who underwent angiography, 59 were excluded from randomization. Among the 46 patients randomized, 40 were treated with rpro-UK (n=26) or placebo (n=14) a median of 5.5 hours from symptom onset. Recanalization was significantly associated with rpro-UK (2P=.017). Hemorrhagic transformation causing neurological deterioration within 24 hours of treatment occurred in 15.4% of the rpro-UK-treated patients and 7.1% of the placebo-treated patients (2P=.64). Both recanalization and hemorrhage frequencies were influenced by heparin dose. CONCLUSIONS: Intra-arterial local rpro-UK infusion was associated with superior recanalization in acute thrombotic/ thromboembolic stroke compared with placebo. In this regimen, heparin dose influenced hemorrhage frequency and recanalization. Although symptomatic hemorrhage remains a concern, this study suggests that recanalization is enhanced with rpro-UK and heparin.

Acute Disease↗
PubMed1998

Is in-hospital stroke mortality an accurate measure of quality of care?

We examined the validity of using in-hospital stroke mortality as predicted by the Cleveland Hospital Outcomes Indicators of Care Evaluations (CHOICE) model as a measure of quality of care. A total of 223 patients admitted to the hospital for stroke were evaluated by the CHOICE model, which predicted that 19 stroke deaths would occur. We reviewed the 19 patients with the highest predicted mortality, according to CHOICE, and three additional patients who died following stroke. We found that The CHOICE model accurately predicts in-hospital stroke mortality for large populations but not for individual patients. CHOICE and other stroke outcome models rely heavily on early Do Not Resuscitate orders and coma but exclude important variables found in the literature on stroke. No correlation between in-hospital stroke mortality and quality of care was demonstrated. Mortality prediction models used to guide consumers on where to receive stroke care are potentially misleading, as they do not assess functional neurologic recovery or the process of care that are essential elements of quality.

Cerebrovascular Disorders↗
PubMed1997

When is thrombolysis justified in patients with acute ischemic stroke? A bioethical perspective.

BACKGROUND: Thrombolytic therapy for acute ischemic stroke raises several unsettled bioethical issues related to risk versus benefit. Excluding the National Institutes of Neurological Disorders and Stroke (NINDS) rt-PA trial, the risk of intracerebral hemorrhage averages 10.3%, and there is a 44% increase in the odds of death among fibrinolysis-treated patients. Some investigators have suggested that as yet unidentified subgroups may benefit despite an increased early risk of hemorrhage and death, while others have warned that the widespread use of thrombolysis cannot currently be recommended despite recent Food and Drug Administration approval. The NINDS rt-PA trial showed a net benefit, but the relative risk to benefit ratio in individual patients is uncertain because of incomplete subgroup analysis. We explore these and related issues by applying the bioethical principle of justification to the selection of stroke patients for thrombolysis. SUMMARY OF COMMENT: Justification of a therapy rests on the criteria of safety, efficacy (net benefit under ideal conditions), effectiveness (net benefit under routine conditions), efficiency (cost-effectiveness or cost benefit), and outcome (proportionality and informed consent). The ethical principal of proportionality states that positive outcomes must be proportional to negative outcomes; only the NINDS trial sets equipoise between risk and benefit. The relative risk to benefit ratio and cost-effectiveness of thrombolysis will likely vary among treating physicians and patient subgroups. Although some potential selection factors such as early CT changes, National Institutes of Health Stroke Scale score > 22, and age > 77 years have been identified, it is not yet possible to predict response to treatment in individual patients. The effectiveness of thrombolysis outside of a clinical trial has not yet been demonstrated, and it is not clear that thrombolysis is cost-effective for all potential patient subgroups. CONCLUSIONS: No stroke thrombolysis regimen has met all five justification criteria. Proportional outcome standards that take into account patient preferences must be established. The risk to benefit ratio of thrombolysis in patient subgroups requires clarification and should incorporate cost-efficiency analyses. These issues should be kept in mind when considering thrombolysis therapy in patients with acute ischemic stroke and when designing clinical trials.

Age Factors↗
PubMed1997

Intra-arterial thrombolysis of embolic proximal middle cerebral artery occlusion from presumed atrial myxoma.

The role of thrombolysis in brain ischemia in patients with atrial myxoma is unknown. A patient with acute brain ischemia and previously undiagnosed atrial myxoma recanalized an occluded middle cerebral artery with intra-arterial thrombolysis. Arterial occlusion from presumed myxoma may be amenable to fibrinolysis. Angiography before treatment in patients with atrial myxoma excludes a myxomatous pseudoaneurysm and permits site-specific thrombolytic instillment.

Carotid Arteries↗