***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 —Cigarette smoking causes endothelial dysfunction , possibly through increased oxidant stress . The enzyme xanthine oxidase produces oxidative free radicals . We tested the hypothesis that xanthine oxidase contributes to endothelial dysfunction in cigarette smokers by administering the inhibitor allopurinol . Methods and Results —Fourteen cigarette smokers ( 31±4 pack years ) and 14 age- and sex-matched healthy non-smoking control subjects participated in a single-blinded , r and omized , 2-phase crossover study . All subjects had no other risk factors for atherosclerosis . Inhibition of xanthine oxidase was achieved by a single oral dose of 600 mg of allopurinol on the day of the study . Stimulated nitric oxide endothelial responses were assessed by forearm blood flow responses to intraarterial administration of acetylcholine and bradykinin 4 to 7 hours later ; basal nitric oxide was assessed using the nitric oxide synthase inhibitor NG-monomethyl-l-arginine ( L-NMMA ) ; and nitroprusside was used to assess sensitivity to nitric oxide . Dilatation produced by acetylcholine was significantly less in smokers ( 254±57 % ) than healthy controls ( 390±55 % ) ( P = 0.009 ) . Allopurinol reversed endothelial dysfunction in smokers ( acetylcholine , 463±78 % , P = 0.001 ) without affecting responses in non-smokers ( 401±80 % ) . Bradykinin responses were also impaired in smokers ( P = 0.003 ) , and improved with allopurinol , though not significantly ( P = 0.06 ) . Responses to nitroprusside and L-NMMA were not significantly different between smokers and controls and were not altered by allopurinol . Conclusions —Smoking-induced endothelial dysfunction of resistance vessels is rapidly reversed with oral allopurinol . These data suggest that xanthine oxidase contributes importantly to endothelial dysfunction caused by cigarette smoking Background —Endothelial function is impaired in coronary artery disease and may contribute to its clinical manifestations . Increased oxidative stress has been linked to impaired endothelial function in atherosclerosis and may play a role in the pathogenesis of cardiovascular events . This study was design ed to determine whether endothelial dysfunction and vascular oxidative stress have prognostic impact on cardiovascular event rates in patients with coronary artery disease . Methods and Results —Endothelium-dependent and -independent vasodilation was determined in 281 patients with documented coronary artery disease by measuring forearm blood flow responses to acetylcholine and sodium nitroprusside using venous occlusion plethysmography . The effect of the coadministration of vitamin C ( 24 mg/min ) was assessed in a subgroup of 179 patients .  Cardiovascular events , including death from cardiovascular causes , myocardial infa rct ion , ischemic stroke , coronary angioplasty , and coronary or peripheral bypass operation , were studied during a mean follow-up period of 4.5 years . Patients experiencing cardiovascular events ( n=91 ) had lower vasodilator responses to acetylcholine ( P < 0.001 ) and sodium nitroprusside ( P < 0.05 ) , but greater benefit from vitamin C ( P < 0.01 ) . The Cox proportional regression analysis for conventional risk factors demonstrated that blunted acetylcholine-induced vasodilation ( P = 0.001 ) , the effect of vitamin C ( P = 0.001 ) , and age ( P = 0.016 ) remained independent predictors of cardiovascular events . Conclusions —Endothelial dysfunction and increased vascular oxidative stress predict the risk of cardiovascular events in patients with coronary artery disease . These data support the concept that oxidative stress may contribute not only to endothelial dysfunction but also to coronary artery disease activity Background —Dilated cardiomyopathy is characterized by an imbalance between left ventricular performance and myocardial energy consumption . Experimental models suggest that oxidative stress result ing from increased xanthine oxidase ( XO ) activity contributes to this imbalance . Accordingly , we hypothesized that XO inhibition with intracoronary allopurinol improves left ventricular efficiency in patients with idiopathic dilated cardiomyopathy . Methods and Results — Patients ( n=9 ; ejection fraction , 29±3 % ) were instrumented to assess myocardial oxygen consumption ( M&OV0312;o2 ) , peak rate of rise of left ventricular pressure ( dP/dtmax ) , stroke work ( SW ) , and efficiency ( dP/dtmax/M&OV0312 ; o2 and SW/M&OV0312;o2 ) at baseline and after sequential infusions of intracoronary allopurinol ( 0.5 , 1.0 , and 1.5 mg/min , each for 15 minutes ) . Allopurinol caused a significant decrease in M&OV0312;o2 ( peak effect , −16±5%;P < 0.01 ; n=9 ) with no parallel decrease in dP/dtmax or SW and no change in ventricular load . The net result was a substantial improvement in myocardial efficiency ( peak effects : dP/dtmax/M&OV0312 ; o2 , 22±9 % , n=9 ; SW/M&OV0312 ; o2 , 40±17 % , n=6 ; both P < 0.05 ) . These effects were apparent despite concomitant treatment with st and ard heart failure therapy , including ACE inhibitors and & bgr;-blockers . XO and its parent enzyme xanthine dehydrogenase were more abundant in failing explanted human myocardium on immunoblot . Conclusions —These findings indicate that XO activity may contribute to abnormal energy metabolism in human cardiomyopathy . By reversing the energetic inefficiency of the failing heart , pharmacological XO inhibition represents a potential novel therapeutic strategy for the treatment of human heart failure Background and Purpose — Elevated serum uric acid level is associated with poor outcome and increased risk of recurrent events after stroke . The xanthine oxidase inhibitor allopurinol lowers uric acid but also attenuates expression of inflammatory adhesion molecules in murine models , reduces oxidative stress in the vasculature , and improves endothelial function . We sought to investigate whether allopurinol alters expression of inflammatory markers after acute ischemic stroke . Methods — We performed a r and omized , double-blind , placebo-controlled trial to investigate the safety , tolerability , and effect of 6 weeks ' treatment with high- ( 300 mg once a day ) or low- ( 100 mg once a day ) dose allopurinol on levels of uric acid and circulating inflammatory markers after ischemic stroke . Results — We enrolled 50 patients with acute ischemic stroke ( 17 , 17 , and 16 in the high , low , and placebo groups , respectively ) . Mean ( ±SD ) age was 70 ( ±13 ) years . Groups had similar characteristics at baseline . There were no serious adverse events . Uric acid levels were significantly reduced at both 7 days and 6 weeks in the high-dose group ( by 0.14 mmol/L at 6 weeks , P=0.002 ) . Intercellular adhesion molecule-1 concentration ( ng/mL ) rose by 51.2 in the placebo group , rose slightly ( by 10.6 ) in the low-dose allopurinol group , but fell in the high-dose group ( by 2.6 ; difference between groups P=0.012 , Kruskal-Wallis test ) . Conclusion — Allopurinol treatment is well tolerated and attenuates the rise in intercellular adhesion molecule-1 levels seen after stroke . Uric acid levels were lowered with high doses . These findings support further evaluation of allopurinol as a preventive measure after stroke Increased oxidative stress in obstructive sleep apnoea is thought to contribute to endothelial dysfunction . The objective of this study was to test the hypothesis that inhibition of xanthine oxidase by allopurinol can improve endothelial function in patients with obstructive sleep apnoea . A r and omised double-blind placebo-controlled crossover study was performed on 12 patients with moderate-to-severe obstructive sleep apnoea , comparing 300 mg allopurinol daily for 2 weeks with placebo . Endothelial function was assessed using hyperaemia-induced flow-mediated vasodilation ( FMD ) at baseline and following treatment . Plasma malondialdehyde levels were compared in order to assess significant changes in oxidative stress . Baseline FMD correlated significantly with the severity of sleep apnoea and the time spent with an arterial oxygen saturation of < 90 % . Allopurinol caused a significant increase in FMD compared to placebo ( 10.4±3.2 versus 7.4±2.8 % , respectively ) . Plasma malondialdehyde levels were significantly reduced with allopurinol treatment ( 1.5±0.3 versus 1.2±0.3 μmol·L−1 ) , consistent with reduced oxidative stress . Allopurinol improves endothelial dysfunction in patients with moderate-to-severe obstructive sleep apnoea . These observations suggest that xanthine oxidase contributes significantly to vasodilatory impairment AIMS Allopurinol improves endothelial function in chronic heart failure by reducing oxidative stress . We wished to explore if such an effect would attenuate autonomic dysfunction in CHF in line with many other effective therapies in CHF . METHODS We performed a prospect i ve , r and omized , double-blind cross-over study in 16 patients with NYHA Class II-IV chronic heart failure ( mean age 67 + /- 10 years , 13 male , comparing allopurinol ( 2 months ) at a daily dose of 300 mg ( if creatinine < 150 micromol l-1 ) or 100 mg ( if creatinine > 150 micromol l-1 ) with matched placebo .  Mean heart rate and dysrhythmia counts were recorded from 24 h Holter tapes at monthly intervals for 6 months . We assessed autonomic function using st and ard time domain heart rate variability parameters ( HRV ) : SDNN , SDANN , SDNN index , rMSSD and TI . RESULTS Allopurinol had no significant effect on heart rate variability compared with placebo ; the results are expressed as a difference in means + /- s.d . with 95 % confidence interval ( CI ) between allopurinol and placebo : SDNN mean = 6.5 + /- 4.8 ms , P = 0.18 and 95 % CI ( -3.7 , 17 ) ; TI mean = -2.1 + /- 1.4 , P = 0.16 and 95 % CI ( -5.2 , 0.8 ) ; SDANN mean = -2.8 + /- 7 ms , P = 0.68 and 95 % CI ( -18 , 12 ) ; SDNNi mean = 2 + /- 6.6 , P = 0.7 and 95 % CI ( -12 , 16 ) ; RMSSD mean = -0.9 + /- 2 , P = 0.68 and 95 % CI ( -5.6 , 3.7 ) . For mean heart rate the corresponding results were 0.9 + /- 1.4 , P = 0.5 and 95 % CI ( -2 , 3.8 ) . Log 24 h ventricular ectopic counts ( VEC ) were 0.032 + /- 0.37 , P = 0.7 and 95 % CI ( -0.1 , 0.2 ) . Patient compliance with study medication was good since allopurinol showed its expected effect of reducing plasma uric acid ( P < 0.001 ) . CONCLUSIONS Allopurinol at doses , which are known to reduce oxidative stress appear to have no significant effect on resting autonomic tone , as indicated by time domain heart rate variability or on dysrhythmia count in stable heart failure patients Background —In patients with chronic heart failure ( CHF ) , hyperuricemia is a common finding and is associated with reduced vasodilator capacity and impaired peripheral blood flow . It has been suggested that the causal link of this association is increased xanthine oxidase (XO)–derived oxygen free radical production and endothelial dysfunction . We therefore studied the effects of XO inhibition with allopurinol on endothelial function and peripheral blood flow in CHF patients after intra-arterial infusion and after oral administration in 2 independent placebo-controlled studies . Methods and Results —In 10 CHF patients with normal serum uric acid ( UA ) levels ( 315±42 & mgr;mol/L ) and 9 patients with elevated UA ( 535±54 & mgr;mol/L ) , endothelium-dependent ( acetylcholine infusion ) and endothelium-independent  ( nitroglycerin infusion ) vasodilation of the radial artery was determined . Coinfusion of allopurinol ( 600 & mgr;g/min ) 
    Output:
    
XOI improves endothelial function and circulating markers of oxidative stress in patients with , or at risk of , cardiovascular disease .