human
***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: Cigarette smoking impairs endothelial function . Hydroxymethylglutaryl ( HMG ) CoA reductase inhibitors ( statins ) may favorably affect endothelial function via nonlipid mechanisms . We tested the hypothesis that statins would improve endothelial function independent of changes in lipids in cigarette smokers . Twenty normocholesterolemic cigarette smokers and 20 matched healthy control subjects were r and omized to atorvastatin 40 mg daily or placebo for 4 weeks , washed out for 4 weeks , and then crossed-over to the other treatment . Baseline low-density lipoprotein ( LDL ) levels were similar in smokers and healthy subjects , 103±22 versus 95±27 mg/dL , respectively ( P = NS ) and were reduced similarly in smokers and control subjects by atorvastatin , to 55±30 and 58±20 mg/dL , respectively ( P = NS ) . Vascular ultrasonography was used to determine brachial artery , flow-mediated , endothelium-dependent , and nitroglycerin-mediated , endothelium-independent vasodilation . To eluci date potential molecular mechanisms that may account for changes in endothelial function , skin biopsy specimens were assayed for eNOS mRNA , eNOS activity , and nitrotyrosine . Endothelium-dependent vasodilation was less in smokers than nonsmoking control subjects during placebo treatment , 8.0±0.6 % versus 12.1±1.1 % , ( P=0.003 ) . Atorvastatin  increased endothelium-dependent vasodilation in smokers to 10.5±1.3 % ( P=0.017 versus placebo ) but did not change endothelium-dependent vasodilation in control subjects ( to 11.0±0.8 % , P = NS ) . Endothelium-independent vasodilation did not differ between groups during placebo treatment and was not significantly affected by atorvastatin . Multivariate analysis did not demonstrate any association between baseline lipid levels or the change in lipid levels and endothelium-dependent vasodilation . Cutaneous nitrotyrosine levels and skin microvessel eNOS mRNA , but not ENOS activity , were increased in smokers compared with controls but unaffected by atorvastatin treatment . Atorvastatin  restores endothelium-dependent vasodilation in normocholesterolemic cigarette smokers independent of changes in lipids . These results are consistent with a lipid-independent vascular benefit of statins but could not be explained by changes in eNOS message and tissue oxidative stress . These findings implicate a potential role for statin therapy to restore endothelial function and thereby investigate vascular disease in cigarette smokers Phosphodiesterase-5 ( PDE-5 ) inhibitors are an effective therapy for the majority of men with erectile dysfunction ( ED ) . However , many men with ED still report a suboptimal or partial response even after an adequate trial of oral PDE-5 therapy . Since ED is associated with impaired vascular function and both atorvastatin and quinapril have been previously shown to improve vascular function , we examined the effects of adjunctive treatment with these medications in men with vasculogenic ED who were suboptimal responders to 100 mg of sildenafil . Men with ED and suboptimal response to sildenafil  were r and omly assigned to 3 months of treatment with atorvastatin 40 mg ( n = 12 ) , quinapril 10 mg ( n = 10 ) , or placebo ( n = 13 ) , along with continued adjunctive sildenafil use . Measured variables included : International Index of Erectile Function ( IIEF ) question naire , brachial artery flow-mediated dilation ( FMD ) , endothelium-independent dilation ( EID ) via nitroglycerin , penile Doppler blood flow , blood pressure ( BP ) , lipids , and C-reactive protein ( CRP ) . Compared to placebo , quinapril ( p < 0.01 ) significantly improved symptoms of ED as measured by the IIEF-5 question naire . There was a trend toward a significant improvement in IIEF-5 with atorvastatin . Similarly , quinapril significantly improved the IIEF ED Domain ( p < 0.05 ) . Other peripheral and penile vascular parameters were unchanged with drug therapy as compared to placebo . In conclusion , treatment with quinapril , in combination with sildenafil , improved ED in men with suboptimal response to sildenafil alone . Atorvastatin demonstrated a trend toward improved ED in this group INTRODUCTION Although penile blood flow ( PBF ) has been recommended as an additional diagnostic test in identifying erectile dysfunction ( ED ) patients at risk for latent cardiovascular disease , no study has ever assessed the possible association of PBF and the relational component of sexual function with incident major cardiovascular events ( MACE ) . AIM The aim of this study is to investigate whether severity of ED , PBF , and other factors related to a couple 's relationship predict incident MACE . METHODS A consecutive series of 1,687 patients was studied . Different clinical , biochemical , and instrumental  ( penile flow at color Doppler ultrasound )  parameters were evaluated . MAIN OUTCOME MEASURES Information on MACE was obtained through the City of Florence Registry Office . RESULTS During a mean follow-up of 4.3 + /- 2.6 years , 139 MACE , 15 of which were fatal , were observed . Cox regression analysis , after adjustment for age and Chronic Disease Score , showed that severe ED predicted MACE ( hazard ratio [ HR ] 1.75 ; 95 % confidence interval 1.10 - 2.78 ; P < 0.05 ) . In addition , lower PBF , evaluated both in flaccid ( before ) and dynamic ( after prostagl and in-E1 stimulation ) conditions , was associated with an increased risk of MACE ( HR = 2.67 [ 1.42 - 5.04 ] and 1.57 [ 1.01 - 2.47 ] , respectively , for flaccid [ < 13 cm/second ] and dynamic [ < 25 cm/second ] peak systolic velocity ; both P < 0.05 ) . Reported high sexual interest in the partner and low sexual interest in the patient proved to have a protective effect against MACE . CONCLUSIONS The investigation of male sexuality , and in particular PBF , and sexual desire , could provide insights not only into present cardiovascular status but also into prospect i ve risk BACKGROUND Sildenafil is a potent inhibitor of cyclic guanosine monophosphate hydrolysis [ corrected ] in the corpus cavernosum and therefore increases the penile response to sexual stimulation . We evaluated the efficacy and safety of sildenafil , administered as needed in two sequential double-blind studies of men with erectile dysfunction of organic , psychogenic , and mixed causes . METHODS In a 24-week dose-response study , 532 men were treated with oral sildenafil  ( 25 , 50 , or 100 mg ) or placebo . In a 12-week , flexible dose-escalation study , 329 different men were treated with sildenafil or placebo , with dose escalation to 100 mg based on efficacy and tolerance . After this dose-escalation study , 225 of the 329 men entered a 32-week , open-label extension study . We assessed efficacy according to the International Index of Erectile Function , a patient log , and a global-efficacy question . RESULTS In the dose-response study , increasing doses of sildenafil were associated with improved erectile function ( P values for increases in scores for questions about achieving and maintaining erections were < 0.001 ) . For the men receiving 100 mg of sildenafil , the mean score for the question about achieving erections was 100 percent higher after treatment than at base line ( 4.0 vs. 2.0 of a possible score of 5 ) . In the last four weeks of treatment in the dose-escalation study , 69 percent of all attempts at sexual intercourse were successful for the men receiving sildenafil , as compared with 22 percent for those receiving placebo ( P<0.001 ) . The mean numbers of successful attempts per month were 5.9 for the men receiving sildenafil and 1.5 for those receiving placebo ( P<0.001 ) . Headache , flushing , and dyspepsia were the most common adverse effects in the dose-escalation study , occurring in 6 percent to 18 percent of the men . Ninety-two percent of the men completed the 32-week extension study . CONCLUSIONS Oral sildenafil is an effective , well-tolerated treatment for men with erectile dysfunction PURPOSE We estimated the incidence of  erectile dysfunction in men 40 to 69 years old at study entry during an average 8.8-year followup , and determined how risk varied with age , socioeconomic status and medical conditions . MATERIAL S AND METHODS Data from a r and omly sample d population based longitudinal study of Massachusetts men were analyzed . A total of 1,709 men completed the baseline interview during 1987 to 1989 and 1,156 survivors completed followup from 1995 to 1997 . The analysis sample consisted of 847 men without erectile dysfunction at baseline and with complete followup information .  Erectile dysfunction was assessed by discriminant analysis of 13 questions from a self-administered sexual function question naire and a single global self-rating question . RESULTS The crude incidence rate for erectile dysfunction was 25.9 cases per 1,000 man-years ( 95 % confidence interval [ CI ] 22.5 to 29.9 ) . The annual incidence rate increased with each decade of age and was 12.4 cases per 1,000 man-years ( 95 % CI 9.0 to 16.9 ) , 29.8 ( 24.0 to 37.0 ) and 46.4 ( 36.9 to 58.4 ) for men 40 to 49 , 50 to 59 and 60 to 69 years old , respectively . The age adjusted risk of erectile dysfunction was higher for men with lower education , diabetes , heart disease and hypertension . Population projections for men 40 to 69 years old suggest that 17,781 new cases of erectile dysfunction in Massachusetts and 617,715 in the United States ( white males only ) are expected annually . CONCLUSIONS Although prevalence estimates and cross-sectional correlates of erectile dysfunction have recently been established , incidence estimates were lacking . Incidence is necessary to assess risk , and plan treatment and prevention strategies . The risk of erectile dysfunction was about 26 cases per 1,000 men annually , and increased with age , lower education , diabetes , heart disease and hypertension BACKGROUND Erectile dysfunction ( ED ) may be one manifestation of a generalized vascular disorder characterized by endothelial dysfunction . Statin drugs may improve endothelial function , even before altering the lipid profile . OBJECTIVE We sought to determine whether the addition of a statin with sildenafil would improve ED in men who initially responded poorly to sildenafil .  METHODS Men with moderate-to-severe ED despite an adequate sildenafil trial were enrolled in this r and omized , double-blind , placebo-controlled pilot study . ED was defined using a vali date d self-administered question naire as a score of < or=16 on the International Index of Erectile Function ( erectile function domain score range of 6 - 30 ) . Improvement in ED score with sildenafil was reassessed at 6 and 12 weeks of treatment with atorvastatin ( 80 mg daily ) or matching placebo . RESULTS Twelve men ( mean age 58 + /- 13 years ) with a mean domain score of 8.2 + /- 6.9 and a mean duration of ED of 3.7 years were enrolled in the study . Treatment with atorvastatin decreased mean low-density lipoprotein cholesterol by 43 % and result ed in an improvement with  sildenafil in domain score of 7.8 ( P = 0.036 ) ; an effect was apparent by 6 weeks . The increase in domain score in placebo patients was not statistically significant . CONCLUSIONS Treatment with atorvastatin improved sexual function and the response to oral sildenafil  in men who did not initially respond to treatment with sildenafil .  The results of this pilot study support the hypothesis that vascular endothelial dysfunction contributes to ED in sildenafil nonresponders and deserves further testing in a large clinical trial The aim of the study is to evaluate the effect of simvastatin in  erectile dysfunction ( ED ) secondary to endothelial dysfunction . This study is a double-blind , r and omized , placebo-controlled , clinical trial in patients with ED and endothelial dysfunction . Patients were r and omized to receive 20 mg simvastatin  ( n=21 ) or placebo  ( n=20 ) daily for 6 months and subsequently 10 mg of vardenafil on dem and for 4 weeks . Serum cholesterol , hormone profile , ultrasensitive C-reactive protein , the International Index of Erectile Dysfunction ( IIEF ) and the ED Index of Treatment Satisfaction were evaluated . There was a significant reduction in serum cholesterol in the treatment group . The hormonal profile remained unaltered 
    Output:
    
agent
RESULTS For the comparison of statins ( + /- sildenafil ) with placebo ( + /- sildenafil ) , the mean International Index of Erectile Function ( IIEF-5 ) ( the st and ardized mean difference [ SMD ] = 3.23 , 95 % confidence interval [ CI ] = -1.65 to 4.80 , P < 0.0001 ) indicated that statins ( + /- sildenafil ) showed statistically significantly greater improvements in the mean IIEF-5 compared with placebo ( + /- sildenafil ) .
For the comparison of statins plus sildenafil with placebo plus sildenafil , the mean IIEF-5 ( SMD = 3.60 , 95 % CI = 2.64 to 4.56 , P < 0.00001 ) , the IIEF domain ( SMD = 4.88 , 95%CI = 3.01 to 6.74 , P < 0.00001 ) , and the global efficacy question ( odds ratio = 6.44 , 95 % CI = 2.92 to 14.23 , P < 0.00001 ) showed that compared with placebo plus sildenafil , statins plus sildenafil clearly improved erectile function .
CONCLUSIONS This meta- analysis indicates that statins ( + /- sildenafil ) may improve ED compared with placebo ( + /- sildenafil )
***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: Cigarette smoking impairs endothelial function . Hydroxymethylglutaryl ( HMG ) CoA reductase inhibitors ( statins ) may favorably affect endothelial function via nonlipid mechanisms . We tested the hypothesis that statins would improve endothelial function independent of changes in lipids in cigarette smokers . Twenty normocholesterolemic cigarette smokers and 20 matched healthy control subjects were r and omized to atorvastatin 40 mg daily or placebo for 4 weeks , washed out for 4 weeks , and then crossed-over to the other treatment . Baseline low-density lipoprotein ( LDL ) levels were similar in smokers and healthy subjects , 103±22 versus 95±27 mg/dL , respectively ( P = NS ) and were reduced similarly in smokers and control subjects by atorvastatin , to 55±30 and 58±20 mg/dL , respectively ( P = NS ) . Vascular ultrasonography was used to determine brachial artery , flow-mediated , endothelium-dependent , and nitroglycerin-mediated , endothelium-independent vasodilation . To eluci date potential molecular mechanisms that may account for changes in endothelial function , skin biopsy specimens were assayed for eNOS mRNA , eNOS activity , and nitrotyrosine . Endothelium-dependent vasodilation was less in smokers than nonsmoking control subjects during placebo treatment , 8.0±0.6 % versus 12.1±1.1 % , ( P=0.003 ) . Atorvastatin  increased endothelium-dependent vasodilation in smokers to 10.5±1.3 % ( P=0.017 versus placebo ) but did not change endothelium-dependent vasodilation in control subjects ( to 11.0±0.8 % , P = NS ) . Endothelium-independent vasodilation did not differ between groups during placebo treatment and was not significantly affected by atorvastatin . Multivariate analysis did not demonstrate any association between baseline lipid levels or the change in lipid levels and endothelium-dependent vasodilation . Cutaneous nitrotyrosine levels and skin microvessel eNOS mRNA , but not ENOS activity , were increased in smokers compared with controls but unaffected by atorvastatin treatment . Atorvastatin  restores endothelium-dependent vasodilation in normocholesterolemic cigarette smokers independent of changes in lipids . These results are consistent with a lipid-independent vascular benefit of statins but could not be explained by changes in eNOS message and tissue oxidative stress . These findings implicate a potential role for statin therapy to restore endothelial function and thereby investigate vascular disease in cigarette smokers Phosphodiesterase-5 ( PDE-5 ) inhibitors are an effective therapy for the majority of men with erectile dysfunction ( ED ) . However , many men with ED still report a suboptimal or partial response even after an adequate trial of oral PDE-5 therapy . Since ED is associated with impaired vascular function and both atorvastatin and quinapril have been previously shown to improve vascular function , we examined the effects of adjunctive treatment with these medications in men with vasculogenic ED who were suboptimal responders to 100 mg of sildenafil . Men with ED and suboptimal response to sildenafil  were r and omly assigned to 3 months of treatment with atorvastatin 40 mg ( n = 12 ) , quinapril 10 mg ( n = 10 ) , or placebo ( n = 13 ) , along with continued adjunctive sildenafil use . Measured variables included : International Index of Erectile Function ( IIEF ) question naire , brachial artery flow-mediated dilation ( FMD ) , endothelium-independent dilation ( EID ) via nitroglycerin , penile Doppler blood flow , blood pressure ( BP ) , lipids , and C-reactive protein ( CRP ) . Compared to placebo , quinapril ( p < 0.01 ) significantly improved symptoms of ED as measured by the IIEF-5 question naire . There was a trend toward a significant improvement in IIEF-5 with atorvastatin . Similarly , quinapril significantly improved the IIEF ED Domain ( p < 0.05 ) . Other peripheral and penile vascular parameters were unchanged with drug therapy as compared to placebo . In conclusion , treatment with quinapril , in combination with sildenafil , improved ED in men with suboptimal response to sildenafil alone . Atorvastatin demonstrated a trend toward improved ED in this group INTRODUCTION Although penile blood flow ( PBF ) has been recommended as an additional diagnostic test in identifying erectile dysfunction ( ED ) patients at risk for latent cardiovascular disease , no study has ever assessed the possible association of PBF and the relational component of sexual function with incident major cardiovascular events ( MACE ) . AIM The aim of this study is to investigate whether severity of ED , PBF , and other factors related to a couple 's relationship predict incident MACE . METHODS A consecutive series of 1,687 patients was studied . Different clinical , biochemical , and instrumental  ( penile flow at color Doppler ultrasound )  parameters were evaluated . MAIN OUTCOME MEASURES Information on MACE was obtained through the City of Florence Registry Office . RESULTS During a mean follow-up of 4.3 + /- 2.6 years , 139 MACE , 15 of which were fatal , were observed . Cox regression analysis , after adjustment for age and Chronic Disease Score , showed that severe ED predicted MACE ( hazard ratio [ HR ] 1.75 ; 95 % confidence interval 1.10 - 2.78 ; P < 0.05 ) . In addition , lower PBF , evaluated both in flaccid ( before ) and dynamic ( after prostagl and in-E1 stimulation ) conditions , was associated with an increased risk of MACE ( HR = 2.67 [ 1.42 - 5.04 ] and 1.57 [ 1.01 - 2.47 ] , respectively , for flaccid [ < 13 cm/second ] and dynamic [ < 25 cm/second ] peak systolic velocity ; both P < 0.05 ) . Reported high sexual interest in the partner and low sexual interest in the patient proved to have a protective effect against MACE . CONCLUSIONS The investigation of male sexuality , and in particular PBF , and sexual desire , could provide insights not only into present cardiovascular status but also into prospect i ve risk BACKGROUND Sildenafil is a potent inhibitor of cyclic guanosine monophosphate hydrolysis [ corrected ] in the corpus cavernosum and therefore increases the penile response to sexual stimulation . We evaluated the efficacy and safety of sildenafil , administered as needed in two sequential double-blind studies of men with erectile dysfunction of organic , psychogenic , and mixed causes . METHODS In a 24-week dose-response study , 532 men were treated with oral sildenafil  ( 25 , 50 , or 100 mg ) or placebo . In a 12-week , flexible dose-escalation study , 329 different men were treated with sildenafil or placebo , with dose escalation to 100 mg based on efficacy and tolerance . After this dose-escalation study , 225 of the 329 men entered a 32-week , open-label extension study . We assessed efficacy according to the International Index of Erectile Function , a patient log , and a global-efficacy question . RESULTS In the dose-response study , increasing doses of sildenafil were associated with improved erectile function ( P values for increases in scores for questions about achieving and maintaining erections were < 0.001 ) . For the men receiving 100 mg of sildenafil , the mean score for the question about achieving erections was 100 percent higher after treatment than at base line ( 4.0 vs. 2.0 of a possible score of 5 ) . In the last four weeks of treatment in the dose-escalation study , 69 percent of all attempts at sexual intercourse were successful for the men receiving sildenafil , as compared with 22 percent for those receiving placebo ( P<0.001 ) . The mean numbers of successful attempts per month were 5.9 for the men receiving sildenafil and 1.5 for those receiving placebo ( P<0.001 ) . Headache , flushing , and dyspepsia were the most common adverse effects in the dose-escalation study , occurring in 6 percent to 18 percent of the men . Ninety-two percent of the men completed the 32-week extension study . CONCLUSIONS Oral sildenafil is an effective , well-tolerated treatment for men with erectile dysfunction PURPOSE We estimated the incidence of  erectile dysfunction in men 40 to 69 years old at study entry during an average 8.8-year followup , and determined how risk varied with age , socioeconomic status and medical conditions . MATERIAL S AND METHODS Data from a r and omly sample d population based longitudinal study of Massachusetts men were analyzed . A total of 1,709 men completed the baseline interview during 1987 to 1989 and 1,156 survivors completed followup from 1995 to 1997 . The analysis sample consisted of 847 men without erectile dysfunction at baseline and with complete followup information .  Erectile dysfunction was assessed by discriminant analysis of 13 questions from a self-administered sexual function question naire and a single global self-rating question . RESULTS The crude incidence rate for erectile dysfunction was 25.9 cases per 1,000 man-years ( 95 % confidence interval [ CI ] 22.5 to 29.9 ) . The annual incidence rate increased with each decade of age and was 12.4 cases per 1,000 man-years ( 95 % CI 9.0 to 16.9 ) , 29.8 ( 24.0 to 37.0 ) and 46.4 ( 36.9 to 58.4 ) for men 40 to 49 , 50 to 59 and 60 to 69 years old , respectively . The age adjusted risk of erectile dysfunction was higher for men with lower education , diabetes , heart disease and hypertension . Population projections for men 40 to 69 years old suggest that 17,781 new cases of erectile dysfunction in Massachusetts and 617,715 in the United States ( white males only ) are expected annually . CONCLUSIONS Although prevalence estimates and cross-sectional correlates of erectile dysfunction have recently been established , incidence estimates were lacking . Incidence is necessary to assess risk , and plan treatment and prevention strategies . The risk of erectile dysfunction was about 26 cases per 1,000 men annually , and increased with age , lower education , diabetes , heart disease and hypertension BACKGROUND Erectile dysfunction ( ED ) may be one manifestation of a generalized vascular disorder characterized by endothelial dysfunction . Statin drugs may improve endothelial function , even before altering the lipid profile . OBJECTIVE We sought to determine whether the addition of a statin with sildenafil would improve ED in men who initially responded poorly to sildenafil .  METHODS Men with moderate-to-severe ED despite an adequate sildenafil trial were enrolled in this r and omized , double-blind , placebo-controlled pilot study . ED was defined using a vali date d self-administered question naire as a score of < or=16 on the International Index of Erectile Function ( erectile function domain score range of 6 - 30 ) . Improvement in ED score with sildenafil was reassessed at 6 and 12 weeks of treatment with atorvastatin ( 80 mg daily ) or matching placebo . RESULTS Twelve men ( mean age 58 + /- 13 years ) with a mean domain score of 8.2 + /- 6.9 and a mean duration of ED of 3.7 years were enrolled in the study . Treatment with atorvastatin decreased mean low-density lipoprotein cholesterol by 43 % and result ed in an improvement with  sildenafil in domain score of 7.8 ( P = 0.036 ) ; an effect was apparent by 6 weeks . The increase in domain score in placebo patients was not statistically significant . CONCLUSIONS Treatment with atorvastatin improved sexual function and the response to oral sildenafil  in men who did not initially respond to treatment with sildenafil .  The results of this pilot study support the hypothesis that vascular endothelial dysfunction contributes to ED in sildenafil nonresponders and deserves further testing in a large clinical trial The aim of the study is to evaluate the effect of simvastatin in  erectile dysfunction ( ED ) secondary to endothelial dysfunction . This study is a double-blind , r and omized , placebo-controlled , clinical trial in patients with ED and endothelial dysfunction . Patients were r and omized to receive 20 mg simvastatin  ( n=21 ) or placebo  ( n=20 ) daily for 6 months and subsequently 10 mg of vardenafil on dem and for 4 weeks . Serum cholesterol , hormone profile , ultrasensitive C-reactive protein , the International Index of Erectile Dysfunction ( IIEF ) and the ED Index of Treatment Satisfaction were evaluated . There was a significant reduction in serum cholesterol in the treatment group . The hormonal profile remained unaltered 
    Output:
    