***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND AND PURPOSE Diaspirin cross-linked hemoglobin ( DCLHb ) is a purified , cell-free human hemoglobin solution . In animal stroke models its use led to a significant reduction in the extent of brain injury . The primary objective of this study was to evaluate the safety of DCLHb in patients with acute ischemic stroke . METHODS DCLHb or saline was administered to 85 patients with acute ischemic stroke in the anterior circulation , within 18 hours of onset of symptoms , in a multicenter , r and omized , single-blind , dose-finding , controlled safety trial , consisting of 3 parts : 12 doses of 25 , 50 , and 100 mg/kg DCLHb over 72 hours . RESULTS DCLHb caused a rapid rise in mean arterial blood pressure . The pressor effect was not accompanied by complications or excessive need for antihypertensive treatment . Two patients in the 100 mg/kg group had adverse events that were possibly drug related : one suffered fatal brain and pulmonary edema , the other transient renal and pancreatic insufficiency . Multivariate logistic regression analysis showed that a severe stroke at baseline and treatment with DCLHb ( OR , 4.0 ; CI , 1.4 to 12.0 ) were independent predictors of a worse outcome ( Rankin Scale score of 3 to 6 ) at 3 months . CONCLUSIONS Outcome scale scores were worse in the DCLHb group , and more serious adverse events and deaths occurred in DCLHb-treated patients than in control patients . We recommend that additional safety studies be performed , preferably with a second generation , genetically engineered hemoglobin BACKGROUND AND PURPOSE Reduction in infa rct volume is the st and ard measure of therapeutic success in animal stroke models . Reduction in infa rct volume has been advocated as a biological surrogate or auxiliary outcome measure for human stroke clinical trials to replace or supplement deficit , disability , and global clinical scales . However , few studies have investigated correlations between infa rct volume and clinical end points in acute ischemic stroke patients . METHODS CT scans at days 6 to 11 were acquired prospect ively in 191 fully eligible patients enrolled in the R and omized Trial of Tirilazad Mesylate in Patients With Acute Stroke ( RANTTAS ) . Patients were enrolled within 6 hours of onset of stroke in any vessel distribution .  Infa rct volume was measured by operator-assisted computerized planimetry . RESULTS One hundred thirty-two patients had visible new supratentorial infa rcts , with median infa rct volume of 28.0 cm3 ( interquartile range , 9.0 to 93.0 cm3 ) . Fifty-nine patients had no visible new infa rct . Correlations with st and ard 3-month outcome scales and mortality were as follows : Barthel Index , r=0.43 ; Glasgow Outcome Scale , r=0.53 ; National Institutes of Health Stroke Scale , r=0.54 ; mortality , r=0.31 . For visible infa rcts alone , correlations were as follows : BI , r=0.46 ; GOS , r=0.59 ; NIHSS , r=0.56 ; mortality , r=0.32 . CONCLUSIONS Subacute CT infa rct volume correlates moderately with 3-month clinical outcome as assessed by widely used neurological and functional assessment scales . The modesty of this linkage constrains the use of infa rct volume as a surrogate end point in ischemic stroke clinical trials BACKGROUND In laboratory animals , cerebral ischaemia is worsened by hyperthermia and improved by hypothermia . Whether these observations apply to human beings with stroke is unknown . We therefore examined the relation between body temperature on admission with acute stroke and various indices of stroke severity and outcome . METHODS In a prospect i ve and consecutive study 390 stroke patients were admitted to hospital within 6 h after stroke ( median 2.4 h ) . We determined body temperature on admission , initial stroke severity , infa rct size , mortality , and outcome in survivors . Stroke severity was measured on admission , weekly , and at discharge on the Sc and inavian Stroke Scale ( SSS ) . Infa rct size was determined by computed tomography . Multiple logistic and linear regression outcome analyses included relevant confounders and potential predictors such as age , gender , stroke severity on admission , body temperature , infections , leucocytosis , diabetes , hypertension , atrial fibrillation , ischaemic heart disease , smoking previous stroke , and comorbidity . FINDINGS Mortality was lower and outcome better in patients with mild hypothermia on admission ; both were worse in patients with hyperthermia . Body temperature was independently related to initial stroke severity ( p < 0.009 ) , infa rct size ( p < 0.0001 ) , mortality ( p < 0.02 ) , and outcome in survivors ( SSS at discharge ) ( p < 0.003 ) . For each 1 degrees C increase in body temperature the relative risk of poor outcome ( death or SSS score on discharge < 30 points ) rose by 2.2 ( 95 % CI 1.4 - 3.5 ) ( p < 0.002 ) . INTERPRETATION We have shown that , in acute human stroke , an association exists between body temperature and initial stroke severity , infa rct size , mortality , and outcome . Only intervention trials of hypothermic treatment can prove whether this relation is causal BACKGROUND AND PURPOSE The great variability of outcome seen in stroke patients has led to an interest in identifying predictors of outcome . The combination of clinical and imaging variables as predictors of stroke outcome in a multivariable risk adjustment model may be more powerful than either alone . The purpose of this study was to determine the multivariable relationship between infa rct volume , 6 clinical variables , and 3-month outcomes in ischemic stroke patients . METHODS Included in the study were 256 eligible patients from the R and omized Trial of Tirilazad Mesylate in Acute Stroke ( RANTTAS ) . Six clinical variables and 1-week infa rct volume were the prespecified predictor variables . The National Institutes of Health Stroke Scale , Barthel Index , and Glasgow Outcome Scale were the outcomes . Multivariable logistic regression techniques were used to develop the model equations , and bootstrap techniques were used for internal validation . Predictive performance of the models was assessed for discrimination with receiver operator characteristic ( ROC ) curves and for calibration with calibration curves . RESULTS The predictive models had areas under the ROC curve of 0.79 to 0.88 and demonstrated nearly ideal calibration curves . The areas under the ROC curves were statistically greater ( P<0.001 ) with both clinical and imaging information combined than with either alone for predicting excellent recovery and death or severe disability . CONCLUSIONS Combined clinical and imaging variables are predictive of 3-month outcome in ischemic stroke patients . Demonstration of this relationship with acute clinical variables and 1-week infa rct information supports future attempts to predict 3-month outcome with all acute variables Background The 21-aminosteroids are a series of compounds design ed to inhibit lipid peroxidation in the cell , and , as such , may have cerebral protective effects . The current study was performed to evaluate the effect of a 21-aminosteroid , tirilazad mesylate ( U74006F ) , on cerebral blood flow , metabolism , and carbon dioxide reactivity . Methods Using a double-blind study design , eight volunteers received tirilazad mesylate  , and eight others received only vehicle . The cerebral blood flow was measured by single photon emission computerized tomography using 133Xe inhalation in the resting condition at the beginning of the study and after infusion of tirilazad mesylate ( 1.5 mg/kg ) or vehicle .  Cerebral oxygen metabolism was calculated from the cerebral blood flow and the measured cerebral arteriovenous oxygen content difference . After both of the above cerebral blood flow measurements , arterial carbon dioxide tension was decreased by voluntary hyperventilation , and , later , Increased by breathing an air/carbon dioxide mixture . The relative changes in cerebral blood flow Induced by the Paco2 , variations were estimated from the changes in the arteriovenous oxygen content difference . Results Blood pressure , pulse rate , and Paco2 , were similar before and after the infusion of tirilazad mesylate in both groups , and there was no difference between the groups . The cerebral blood flow and oxygen metabolism did not change after the tirilazad mesylate infusion . The slope of the regression line of relative change of estimated cerebral blood flow and Paco2 , ( regression coefficients in both groups , > 0.90 ) was unchanged after Infusion . Conclusions Tirilazad mesylate has no effect on cerebral blood flow , cerebral oxygen metabolism , or reactivity of cerebral blood flow to carbon dioxide in healthy volunteers 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 r and omized , 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 infa rct ion signs on computed tomographic scan . INTERVENTION Patients were r and omized 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 CONTEXT Approved treatment options for acute ischemic stroke in the United States and Canada are limited at present to intravenous tissue-type plasminogen activator , but bleeding complications , including intracranial hemorrhage , are a recognized complication . OBJECTIVE To evaluate the efficacy and safety of the defibrinogenating agent ancrod in patients with acute ischemic stroke . DESIGN The Stroke Treatment with Ancrod Trial ( STAT ) , a r and omized , parallel-group , double-blind , placebo-controlled trial conducted between August 1993 and January 1998 . SETTING Forty-eight centers , primarily community hospitals , in the United States and Canada . PATIENTS A total of 500 patients with an acute or progressing ischemic neurological deficit were enrolled and included in the intent-to-treat analysis . INTERVENTIONS Patients were r and omly assigned to receive ancrod ( n=248 ) or placebo ( n = 252 ) as a continuous 72-hour intravenous infusion beginning within 3 hours of stroke onset , followed by infusions lasting approximately 1 hour at 96 and 120 hours . The ancrod regimen was design ed to decrease plasma fibrinogen levels to 1.18 to 2.03 micromol/L. MAIN OUTCOME MEASURES The primary efficacy end point was functional status , with favorable functional status defined as survival to day 90 with a Barthel Index of 95 or more or at least the prestroke value , compared by treatment group . Primary safety variables included symptomatic intracranial hemorrhage and mortality . RESULTS Favorable functional status was achieved by more patients in the ancrod group ( 42.2 % ) than in the placebo group ( 34.4 % ; P=.04 ) by the prespecified covariate-adjusted analysis . Mortality was not different between treatment groups ( at 90 days , 25.4 % for the ancrod group and 23 % for the placebo group ; P=.62 ) , and the proportion of severely disabled patients was less in the ancrod group than in the placebo group ( 11.8 % vs 19.8 % ; P=.01 ) . The favorable functional status observed with ancrod vs placebo was consistent in 
    Output:
    
REVIEW ER 'S CONCLUSIONS Tirilazad mesylate increased the combined end-point of ' death or disability ' by about one-fifth , but did not alter case fatality , when given to patients with acute ischaemic stroke .