***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 — In animal models , the combination of caffeine and ethanol ( caffeinol ) provides robust neuroprotection at blood levels that should be easily and safely achieved in humans . This study was design ed to determine the safety and tolerability of ascending doses of this combination in stroke patients . Methods — This Food and Drug Administration – approved open-label , single-arm , dose-escalation study had 3 original dose groups : group 1 , caffeine 6 mg/kg plus ethanol 0.2 g/kg ; groups 2 and 3 , incremental increases of caffeine and ethanol by 2 mg/kg and 0.2 g/kg , respectively . Intravenous thrombolysis was encouraged if patients qualified . Drug was started within 6 hours of stroke onset , and blood levels of caffeine and ethanol were drawn at baseline and end of infusion . The target blood caffeine and ethanol ranges were 8 to 10 & mgr;g/mL and 30 to 50 mg/dL , respectively . Clinical outcome measurements included the National Institutes of Health Stroke Scale at the end of infusion , at 24 hours , and at discharge . Potential complications from caffeine and ethanol were recorded . Cases were review ed by an independent stroke neurologist for safety . Results — A total of 23 patients were recruited .  Target blood caffeine and ethanol levels were reached in 0 of the 4 patients in the first group . The second dose group ( caffeine 8 mg/kg plus ethanol 0.4 g/kg ) included 8 patients . The median end-of-infusion caffeine and ethanol levels were within the desired target ranges . Two days after infusion , 1 patient in this group with preexisting cardiac disease and end-of-infusion caffeine and ethanol levels of 10.7 & mgr;g/mL and 69 mg/dL developed reversible congestive heart failure and required transfer to an intensive care unit . The original third dose group was canceled given achievement of target blood caffeine and ethanol levels in group 2 . However , 3 new dose groups were created in an attempt to minimize the dose of ethanol . Although blood levels were proportional to dose , none of these new dose groups provided optimal blood levels . Congestive heart failure occurred in 1 other patient with previously asymptomatic cardiomyopathy . No other side effects were noted . Concomitant thrombolytic therapy was given in 8 patients , 1 of whom died of intracerebral hemorrhage . Conclusions — Caffeinol alone or combined with intravenous tissue plasminogen activator can be administered safely . Caffeine 8 mg/kg plus ethanol 0.4 g/kg produces target caffeine and ethanol levels of 8 to 10 & mgr;g/mL and 30 to 50 mg/dL , respectively . A r and omized , placebo-controlled trial is needed to determine the neuroprotective effect of this combination In patients with acute ischemic stroke , dramatic but often transient improvements have been noticed after theophylline injections . Whether better results could be obtained by continuous infusion of the drug was evaluated in a double‐blind study . Out of 46 patients with a mean age of 75 years , 22 got theophylline as aminophylline ( bolus dose of 230 mg followed by 0.5 mg/kg/h ) and 24 placebo during 3 days . The groups were comparable in all aspects at the outset of the trial . Serum theophylline concentrations were kept within the therapeutic range recommended for patients with asthma .  No significant difference in outcome was noticed between the groups during the hospital period when repeated neurological assessment s by two different scores and mortality were compared Acute ingestion of caffeine is known to reduce cerebral blood flow in normal volunteers and in certain patient groups . There is no evidence that this causes problems in the normal population . However , there may be implication s if a similar reduction occurs in patients recovering from an ischaemic stroke , in whom local blood flow has already been reduced . Transcranial Doppler provides a non-invasive method for measuring changes in middle cerebral artery ( mca ) blood velocity . A method for obtaining consistent . reliable measurements was developed and used in a double blind , r and omized , crossover study on 20 patients ( 18 M , 2 F ; mean age 70 ) recovering from ischaemic stroke in the mca territory .  Middle cerebral artery blood velocity was measured bilaterally using transcranial Doppler before and after 250 mg caffeine ( equivalent to about two cups of filter coffee ) or matched placebo . Caffeine caused an average 12 % reduction in blood velocity compared to placebo in the hemisphere affected by the stroke ( 95%c CI 8%-16 % , p < 0.00001 ) , and a 12 % reduction in the non-affected hemisphere ( 95 % CI 6%-18 % , p < 0.001 ) . The clinical implication s are unclear at present , and imaging techniques will be required to establish whether caffeine does reduce flow to hypo-perfused regions In a double‐blind trial intravenous aminophylline was compared with placebo in 79 patients with acute cerebral infa rct ion . Immediate improvement in the neurological evaluation score was significantly more frequent in patients receiving aminophylline ( 38 per cent ) than in those on placebo ( 15 per cent ) ; only patients with mild or moderately severe strokes responded to the injection . After 3 weeks , however , the treated patients did not fare significantly better than the controls in terms of neurological score and residual disability . Survival rate , length of stay in hospital , and social readaptation were similar in the two groups . It is concluded that intravenous aminophylline in patients with ischaemic strokes can bring about an immediate symptomatic relief , but without appreciably influencing the ultimate recovery 
    Output:
    
REVIEW ERS ' CONCLUSIONS There is not enough evidence to assess whether theophylline or its analogues , e.g. aminophylline , are safe and improve outcome in people with acute ischaemic stroke