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: Background —We previously reported beneficial effects of pentoxifylline , a xanthine-derived agent known to inhibit the production of tumor necrosis factor-&agr ; , in patients with idiopathic dilated cardiomyopathy treated with diuretics , digoxin , and ACE inhibitors .  Since then , 3 large clinical trials showed important clinical benefits of & bgr;-blockers in this population . Therefore , we design ed the present study to establish whether in patients with heart failure already receiving treatment with ACE inhibitors and & bgr;-blockers , the addition of pentoxifylline would have an additive beneficial effect . Methods and Results —In a single-center , prospect i ve , double-blind , r and omized , placebo-controlled study , 39 patients with idiopathic dilated cardiomyopathy were r and omized to pentoxifylline 400 mg TID ( n=20 ) or placebo ( n=19 ) if they had a left ventricular ejection fraction < 40 % after 3 months of therapy with digoxin , ACE inhibitors , and carvedilol . Primary end points were New York Heart Association functional class , exercise tolerance , and left ventricular function . Patients were followed up for 6 months . Five patients died ( 3 in the placebo group ) . Patients treated with pentoxifylline had a significant improvement in functional class compared with the placebo group ( P = 0.01 ) , with an increment in exercise time from 9.5±5 to 12.3±6 minutes ( P = 0.1 ) . Left ventricular ejection fraction improved from 24±9 % to 31±13 % , P = 0.03 , in the treatment group . Conclusions —In patients with idiopathic dilated cardiomyopathy , the addition of pentoxifylline to treatment with digoxin , ACE inhibitors , and carvedilol is associated with a significant improvement in symptoms and left ventricular function BACKGROUND Since inflammation is believed to have a role in the pathogenesis of cardiovascular events , measurement of markers of inflammation has been proposed as a method to improve the prediction of the risk of these events . METHODS We conducted a prospect i ve , nested case-control study among 28,263 apparently healthy postmenopausal women over a mean follow-up period of three years to assess the risk of cardiovascular events associated with base-line levels of markers of inflammation . The markers included high-sensitivity C-reactive protein ( hs-CRP ) , serum amyloid A , interleukin-6 , and soluble intercellular adhesion molecule type 1 ( sICAM-1 ) . We also studied homocysteine and a variety of lipid and lipoprotein measurements .  Cardiovascular events were defined as death from coronary heart disease , nonfatal myocardial infa rct ion or stroke , or the need for coronary-revascularization procedures . RESULTS Of the 12 markers measured , hs-CRP was the strongest univariate predictor of the risk of cardiovascular events ; the relative risk of events for women in the highest as compared with the lowest quartile for this marker was 4.4 ( 95 percent confidence interval , 2.2 to 8.9 ) . Other markers significantly associated with the risk of cardiovascular events were serum amyloid A ( relative risk for the highest as compared with the lowest quartile , 3.0 ) , sICAM-1 ( 2.6 ) , interleukin-6 ( 2.2 ) , homocysteine ( 2.0 ) , total cholesterol ( 2.4 ) , LDL cholesterol ( 2.4 ) , apolipoprotein B-100 ( 3.4 ) , HDL cholesterol ( 0.3 ) , and the ratio of total cholesterol to HDL cholesterol ( 3.4 ) . Prediction models that incorporated markers of inflammation in addition to lipids were significantly better at predicting risk than models based on lipid levels alone ( P<0.001 ) . The levels of hs-CRP and serum amyloid A were significant predictors of risk even in the subgroup of women with LDL cholesterol levels below 130 mg per deciliter ( 3.4 mmol per liter ) , the target for primary prevention established by the National Cholesterol Education Program . In multivariate analyses , the only plasma markers that independently predicted risk were hs-CRP ( relative risk for the highest as compared with the lowest quartile , 1.5 ; 95 percent confidence interval , 1.1 to 2.1 ) and the ratio of total cholesterol to HDL cholesterol ( relative risk , 1.4 ; 95 percent confidence interval , 1.1 to 1.9 ) . CONCLUSIONS The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying persons at risk for cardiovascular events Despite the beneficial effects of blockade of the renin-angiotensin system in diabetic nephropathy ( DN ) , albuminuria and progression of renal disease are not completely halted by these agents . Therefore , it is necessary to explore potential antiproteinuric and renoprotective effects of innovative therapeutic approaches . This study tested the hypothesis that the combination of pentoxifylline ( PTF ) with angiotensin II receptor blockers in normotensive patients with type 2 diabetes produces an additive antiproteinuric effect .  Sixty-one patients with DN and residual albuminuria despite treatment with the recommended doses of ARB for > 1 yr were r and omly assigned to receive the addition of 1200 mg of PTF daily ( n = 30 ) or to a control group ( n = 31 ) . Baseline characteristics were similar between groups , and correlation analysis showed a significant association between urinary albumin excretion ( UAE ) and urinary TNF-alpha ( R = 0.53 , P < 0.001 ) . After 4 mo , albuminuria showed a significant decrease in patients who received PTF , from 900 mg/24 h ( 466 to 1542 mg/d ) to 791 mg/24 h ( 309 to 1400 mg/d ; P < 0.001 ) , whereas no significant changes were observed in the control group : 920 mg/24 h ( 450 to 1489 mg/d ) at baseline , and 900 mg/24 h ( 428 to 1800 mg/d ) at the end of the study . The mean percentage variation of UAE in the treatment and control groups was -16.7 and 5.5 % , respectively ( between-group comparison , P < 0.001 ) . This additive antiproteinuric effect was not dependent on changes in BP or metabolic control . However , both serum and urinary levels of TNF-alpha also decreased in patients who received PTF , from 6.4 pg/ml ( 2.1 to 9.7 ) and 16 pg/mg ( 8 to 29 ) at baseline to 4.6 pg/ml ( 0.4 to 9 ) and 14.2 pg/mg ( 3 to 26 ) at the end of the study , respectively ( P < 0.01 ) , without significant variations in control patients . Moreover , regression analysis at the end of the study showed a correlation between the change in UAE and the change in urinary TNF-alpha in patients who were treated with PTF ( R = 0.49 , P < 0.001 ) . In conclusion , administration of PTF to patients who have type 2 diabetes and are under long-term treatment with an ARB produces a significant additive antiproteinuric effect associated with a reduction of urinary TNF-alpha excretion Background —Inflammatory immune activation commonly occurs in heart failure and may perpetuate this syndrome . We sought to determine whether the immunomodulating agent pentoxifylline enhances left ventricular function in patients with ischemic cardiomyopathy . We also investigated the effect of therapy on levels of brain natriuretic peptide ( NT-pro BNP ) , C-reactive protein ( CRP ) , tumor necrosis factor-&agr ; ( TNF-&agr ; ) , and the marker of apoptosis , Fas/Apo-1 . Methods and Results —In a single-center , prospect i ve , r and omized , double-blind , placebo-controlled  study , 38 patients with ischemic cardiomyopathy received pentoxifylline 400 mg TID or placebo in addition to st and ard therapy .  Clinical assessment , radionuclide ventriculography , echocardiography , and blood analyses were performed at baseline and after 6 months . There were no differences in baseline characteristics between the groups . Five patients died  ( 4 in the placebo group ) . Pentoxifylline treatment result ed in an improvement in functional class ( P < 0.005 ) and an increase in systolic blood pressure ( P < 0.05 ) and left ventricular radionuclide ejection fraction ( P < 0.05 ) compared with the placebo-treated group . There were reductions in plasma concentrations of CRP , NT-pro BNP , TNF-&agr ; , and Fas/Apo-1 in the pentoxifylline compared with the placebo-treated group . Conclusions —In patients with heart failure due to ischemic left ventricular dysfunction , the addition of pentoxifylline to st and ard therapy results in improvements in clinical status and radionuclide ejection fraction , which are accompanied by reductions in plasma markers of inflammation , prognosis , and apoptosis Background Untreated HIV may increase the risk of cardiovascular events . Our preliminary in vitro and in vivo research suggests that pentoxifylline ( PTX ) reduces vascular inflammation and improves endothelial function in HIV-infected persons not requiring antiretroviral therapy . Methods We performed a r and omized , placebo-controlled trial of PTX 400 mg orally thrice daily for 8 weeks in 26 participants . The primary endpoint was change in flow-mediated dilation ( FMD ) of the brachial artery after 8 weeks . Nitroglycerin-mediated dilation ( NTGMD ) and circulating markers of inflammation , cellular immune activation , coagulation , and metabolism were also assessed . Results The difference in mean absolute change ( SD ) in FMD after 8 weeks between the placebo [ −1.06 (1.45)% ] and PTX [ −1.93 (3.03)% ] groups was not significant ( P = 0.44 ) . No differences in NTGMD were observed . The only significant between-group difference in the changes in biomarkers from baseline to week 8 was in soluble tumor necrosis factor receptor-1 ( sTNFRI ) [ −83.2 pg/mL in the placebo group vs. + 65.9 pg/mL in the PTX group ; P = 0.03 ] . PTX was generally well-tolerated . Conclusions PTX did not improve endothelial function and unexpectedly increased the inflammatory biomarker sTNFRI in HIV-infected participants not requiring antiretroviral therapy . Additional interventional research is needed to reduce inflammation and cardiovascular risk in this population . Trial Registration Clinical Trials.gov Although blockade of renin-angiotensin system have been cited as the first line of therapy for the management of diabetic nephropathy ( DN ) , however in a substantial number of patients , progression of renal disease are not completely halted by these agents . We have conducted a double blinded clinical trial to assess the additive effect of pentoxifylline on reduction of proteinuria among patients with type 2 DM under blockade of angiotensin system . The dosage of PTX used in our trial was at a low dosage of 400 mg daily and to our knowledge , we did not found article which evaluated the antiproteinuric effect of pentoxifylline in this dosage . One hundred patients with DN and persistent proteinuria despite treatment with losartan and enalapril in at least 3 months before inclusion in the study were r and omly assigned to two groups . Control group ( n=50 , 26 males and 24 females ) received losartan and enalapril , while treatment group ( PTX Group ) ( n=50 , 28 males and 22 females ) was given losartan , enalapril and pentoxifylline 400mg/day for 6 months . At the beginning of the study there were no significant differences in demographic and clinical characteristics of patients including serum creatinine , HbA1c , blood pressure and urinary protein excretion between two groups ( P>.05 ) . In the PTX group , the mean rate of urinary protein excretion have significantly decreased from 616.66 mg to 378.24 after 3 months ( P=.000 ) and to 192.05 mg after 6 months ( P=.000 ) whereas no significant changes were observed in the control group . The beneficial antiproteinuric effect of PTX was not associated to the degree of metabolic control and a reduction of blood pressure . In addition , at the end of study , the mean clearance of creatinine was significantly higher in PTX group ( P=.04 ) . In conclusion , PTX can significantly provide additive antiproteinuric effect and slow the decrease in GFR among patients with type 2 DM under blockade of angiotensin system INTRODUCTION The burden of non-alcoholic steatohepatitis ( NASH ) is growing and current pharmacologic treatments are limited by side effects and inconsistent efficacy . Pilot studies suggest that pentoxifylline ( PTX ) can reduce liver injury in patients with NASH . OBJECTIVE We sought to determine the tolerability of PTX and its effect on aminotransferases and liver histology in patients with NASH . MATERIAL AND METHODS Thirty patients with bi 
    Output:
    
agent
No alteration in plasma IL-6 concentration was observed .
Pentoxifylline did not alter BP or plasma IL-6 concentration , but significantly reduced circulating TNF-α and CRP concentrations
***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 —We previously reported beneficial effects of pentoxifylline , a xanthine-derived agent known to inhibit the production of tumor necrosis factor-&agr ; , in patients with idiopathic dilated cardiomyopathy treated with diuretics , digoxin , and ACE inhibitors .  Since then , 3 large clinical trials showed important clinical benefits of & bgr;-blockers in this population . Therefore , we design ed the present study to establish whether in patients with heart failure already receiving treatment with ACE inhibitors and & bgr;-blockers , the addition of pentoxifylline would have an additive beneficial effect . Methods and Results —In a single-center , prospect i ve , double-blind , r and omized , placebo-controlled study , 39 patients with idiopathic dilated cardiomyopathy were r and omized to pentoxifylline 400 mg TID ( n=20 ) or placebo ( n=19 ) if they had a left ventricular ejection fraction < 40 % after 3 months of therapy with digoxin , ACE inhibitors , and carvedilol . Primary end points were New York Heart Association functional class , exercise tolerance , and left ventricular function . Patients were followed up for 6 months . Five patients died ( 3 in the placebo group ) . Patients treated with pentoxifylline had a significant improvement in functional class compared with the placebo group ( P = 0.01 ) , with an increment in exercise time from 9.5±5 to 12.3±6 minutes ( P = 0.1 ) . Left ventricular ejection fraction improved from 24±9 % to 31±13 % , P = 0.03 , in the treatment group . Conclusions —In patients with idiopathic dilated cardiomyopathy , the addition of pentoxifylline to treatment with digoxin , ACE inhibitors , and carvedilol is associated with a significant improvement in symptoms and left ventricular function BACKGROUND Since inflammation is believed to have a role in the pathogenesis of cardiovascular events , measurement of markers of inflammation has been proposed as a method to improve the prediction of the risk of these events . METHODS We conducted a prospect i ve , nested case-control study among 28,263 apparently healthy postmenopausal women over a mean follow-up period of three years to assess the risk of cardiovascular events associated with base-line levels of markers of inflammation . The markers included high-sensitivity C-reactive protein ( hs-CRP ) , serum amyloid A , interleukin-6 , and soluble intercellular adhesion molecule type 1 ( sICAM-1 ) . We also studied homocysteine and a variety of lipid and lipoprotein measurements .  Cardiovascular events were defined as death from coronary heart disease , nonfatal myocardial infa rct ion or stroke , or the need for coronary-revascularization procedures . RESULTS Of the 12 markers measured , hs-CRP was the strongest univariate predictor of the risk of cardiovascular events ; the relative risk of events for women in the highest as compared with the lowest quartile for this marker was 4.4 ( 95 percent confidence interval , 2.2 to 8.9 ) . Other markers significantly associated with the risk of cardiovascular events were serum amyloid A ( relative risk for the highest as compared with the lowest quartile , 3.0 ) , sICAM-1 ( 2.6 ) , interleukin-6 ( 2.2 ) , homocysteine ( 2.0 ) , total cholesterol ( 2.4 ) , LDL cholesterol ( 2.4 ) , apolipoprotein B-100 ( 3.4 ) , HDL cholesterol ( 0.3 ) , and the ratio of total cholesterol to HDL cholesterol ( 3.4 ) . Prediction models that incorporated markers of inflammation in addition to lipids were significantly better at predicting risk than models based on lipid levels alone ( P<0.001 ) . The levels of hs-CRP and serum amyloid A were significant predictors of risk even in the subgroup of women with LDL cholesterol levels below 130 mg per deciliter ( 3.4 mmol per liter ) , the target for primary prevention established by the National Cholesterol Education Program . In multivariate analyses , the only plasma markers that independently predicted risk were hs-CRP ( relative risk for the highest as compared with the lowest quartile , 1.5 ; 95 percent confidence interval , 1.1 to 2.1 ) and the ratio of total cholesterol to HDL cholesterol ( relative risk , 1.4 ; 95 percent confidence interval , 1.1 to 1.9 ) . CONCLUSIONS The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying persons at risk for cardiovascular events Despite the beneficial effects of blockade of the renin-angiotensin system in diabetic nephropathy ( DN ) , albuminuria and progression of renal disease are not completely halted by these agents . Therefore , it is necessary to explore potential antiproteinuric and renoprotective effects of innovative therapeutic approaches . This study tested the hypothesis that the combination of pentoxifylline ( PTF ) with angiotensin II receptor blockers in normotensive patients with type 2 diabetes produces an additive antiproteinuric effect .  Sixty-one patients with DN and residual albuminuria despite treatment with the recommended doses of ARB for > 1 yr were r and omly assigned to receive the addition of 1200 mg of PTF daily ( n = 30 ) or to a control group ( n = 31 ) . Baseline characteristics were similar between groups , and correlation analysis showed a significant association between urinary albumin excretion ( UAE ) and urinary TNF-alpha ( R = 0.53 , P < 0.001 ) . After 4 mo , albuminuria showed a significant decrease in patients who received PTF , from 900 mg/24 h ( 466 to 1542 mg/d ) to 791 mg/24 h ( 309 to 1400 mg/d ; P < 0.001 ) , whereas no significant changes were observed in the control group : 920 mg/24 h ( 450 to 1489 mg/d ) at baseline , and 900 mg/24 h ( 428 to 1800 mg/d ) at the end of the study . The mean percentage variation of UAE in the treatment and control groups was -16.7 and 5.5 % , respectively ( between-group comparison , P < 0.001 ) . This additive antiproteinuric effect was not dependent on changes in BP or metabolic control . However , both serum and urinary levels of TNF-alpha also decreased in patients who received PTF , from 6.4 pg/ml ( 2.1 to 9.7 ) and 16 pg/mg ( 8 to 29 ) at baseline to 4.6 pg/ml ( 0.4 to 9 ) and 14.2 pg/mg ( 3 to 26 ) at the end of the study , respectively ( P < 0.01 ) , without significant variations in control patients . Moreover , regression analysis at the end of the study showed a correlation between the change in UAE and the change in urinary TNF-alpha in patients who were treated with PTF ( R = 0.49 , P < 0.001 ) . In conclusion , administration of PTF to patients who have type 2 diabetes and are under long-term treatment with an ARB produces a significant additive antiproteinuric effect associated with a reduction of urinary TNF-alpha excretion Background —Inflammatory immune activation commonly occurs in heart failure and may perpetuate this syndrome . We sought to determine whether the immunomodulating agent pentoxifylline enhances left ventricular function in patients with ischemic cardiomyopathy . We also investigated the effect of therapy on levels of brain natriuretic peptide ( NT-pro BNP ) , C-reactive protein ( CRP ) , tumor necrosis factor-&agr ; ( TNF-&agr ; ) , and the marker of apoptosis , Fas/Apo-1 . Methods and Results —In a single-center , prospect i ve , r and omized , double-blind , placebo-controlled  study , 38 patients with ischemic cardiomyopathy received pentoxifylline 400 mg TID or placebo in addition to st and ard therapy .  Clinical assessment , radionuclide ventriculography , echocardiography , and blood analyses were performed at baseline and after 6 months . There were no differences in baseline characteristics between the groups . Five patients died  ( 4 in the placebo group ) . Pentoxifylline treatment result ed in an improvement in functional class ( P < 0.005 ) and an increase in systolic blood pressure ( P < 0.05 ) and left ventricular radionuclide ejection fraction ( P < 0.05 ) compared with the placebo-treated group . There were reductions in plasma concentrations of CRP , NT-pro BNP , TNF-&agr ; , and Fas/Apo-1 in the pentoxifylline compared with the placebo-treated group . Conclusions —In patients with heart failure due to ischemic left ventricular dysfunction , the addition of pentoxifylline to st and ard therapy results in improvements in clinical status and radionuclide ejection fraction , which are accompanied by reductions in plasma markers of inflammation , prognosis , and apoptosis Background Untreated HIV may increase the risk of cardiovascular events . Our preliminary in vitro and in vivo research suggests that pentoxifylline ( PTX ) reduces vascular inflammation and improves endothelial function in HIV-infected persons not requiring antiretroviral therapy . Methods We performed a r and omized , placebo-controlled trial of PTX 400 mg orally thrice daily for 8 weeks in 26 participants . The primary endpoint was change in flow-mediated dilation ( FMD ) of the brachial artery after 8 weeks . Nitroglycerin-mediated dilation ( NTGMD ) and circulating markers of inflammation , cellular immune activation , coagulation , and metabolism were also assessed . Results The difference in mean absolute change ( SD ) in FMD after 8 weeks between the placebo [ −1.06 (1.45)% ] and PTX [ −1.93 (3.03)% ] groups was not significant ( P = 0.44 ) . No differences in NTGMD were observed . The only significant between-group difference in the changes in biomarkers from baseline to week 8 was in soluble tumor necrosis factor receptor-1 ( sTNFRI ) [ −83.2 pg/mL in the placebo group vs. + 65.9 pg/mL in the PTX group ; P = 0.03 ] . PTX was generally well-tolerated . Conclusions PTX did not improve endothelial function and unexpectedly increased the inflammatory biomarker sTNFRI in HIV-infected participants not requiring antiretroviral therapy . Additional interventional research is needed to reduce inflammation and cardiovascular risk in this population . Trial Registration Clinical Trials.gov Although blockade of renin-angiotensin system have been cited as the first line of therapy for the management of diabetic nephropathy ( DN ) , however in a substantial number of patients , progression of renal disease are not completely halted by these agents . We have conducted a double blinded clinical trial to assess the additive effect of pentoxifylline on reduction of proteinuria among patients with type 2 DM under blockade of angiotensin system . The dosage of PTX used in our trial was at a low dosage of 400 mg daily and to our knowledge , we did not found article which evaluated the antiproteinuric effect of pentoxifylline in this dosage . One hundred patients with DN and persistent proteinuria despite treatment with losartan and enalapril in at least 3 months before inclusion in the study were r and omly assigned to two groups . Control group ( n=50 , 26 males and 24 females ) received losartan and enalapril , while treatment group ( PTX Group ) ( n=50 , 28 males and 22 females ) was given losartan , enalapril and pentoxifylline 400mg/day for 6 months . At the beginning of the study there were no significant differences in demographic and clinical characteristics of patients including serum creatinine , HbA1c , blood pressure and urinary protein excretion between two groups ( P>.05 ) . In the PTX group , the mean rate of urinary protein excretion have significantly decreased from 616.66 mg to 378.24 after 3 months ( P=.000 ) and to 192.05 mg after 6 months ( P=.000 ) whereas no significant changes were observed in the control group . The beneficial antiproteinuric effect of PTX was not associated to the degree of metabolic control and a reduction of blood pressure . In addition , at the end of study , the mean clearance of creatinine was significantly higher in PTX group ( P=.04 ) . In conclusion , PTX can significantly provide additive antiproteinuric effect and slow the decrease in GFR among patients with type 2 DM under blockade of angiotensin system INTRODUCTION The burden of non-alcoholic steatohepatitis ( NASH ) is growing and current pharmacologic treatments are limited by side effects and inconsistent efficacy . Pilot studies suggest that pentoxifylline ( PTX ) can reduce liver injury in patients with NASH . OBJECTIVE We sought to determine the tolerability of PTX and its effect on aminotransferases and liver histology in patients with NASH . MATERIAL AND METHODS Thirty patients with bi 
    Output:
    