***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: Bosentan ( Ro 47‐0203 ) is a potent and mixed ETA‐ and ETB‐receptor antagonist . Its activity has been studied in a variety of pre clinical disease models Objectives Ischaemic digital ulcers ( DUs ) are common in patients with systemic sclerosis ( SSc ) and are a cause of disease-related morbidity . In an earlier trial , treatment with bosentan , an oral endothelin receptor antagonist , reduced the occurrence of new DUs by 48 % . The present study ( RAPIDS-2 , for ‘ R And omized , double-blind , Placebo-controlled study with bosentan on healing and prevention of Ischemic Digital ulcers in patients with systemic Sclerosis ’ ) was conducted to more fully evaluate the effects of bosentan treatment on DUs associated with SSc . Methods This double-blind , placebo-controlled trial conducted at 41 centres in Europe and North America r and omised 188 patients with SSc with at least 1 active DU ( ‘ cardinal ulcer ’ ) to bosentan 62.5 mg twice daily for 4 weeks and 125 mg twice daily thereafter for 20 weeks ( n=98 ) or matching placebo ( n=90 ; total 24 weeks ) . The two primary end points were the number of new DUs and the time to healing of the cardinal ulcer . Secondary end points included pain , disability and safety . Results Over 24 weeks , bosentan treatment was associated with a 30 % reduction in the number of new DUs  compared with placebo ( mean±st and ard error : 1.9±0.2 vs 2.7±0.3 new ulcers ; p=0.04 ) . This effect was greater in patients who entered the trial with more DUs . There was no difference between treatments in healing rate of the cardinal ulcer or secondary end points of pain and disability . Peripheral oedema and elevated aminotransferases were associated with bosentan treatment . Conclusions Bosentan treatment reduced the occurrence of new DUs in patients with SSc but had no effect on DU healing . Bosentan was well tolerated and may be a useful adjunct in the management of patients with SSc with recurrent DUs Treatment with pyridinolcarbamate for obstructive diseases of the peripheral arteries could be evaluated in 21 patients . The results of the treatment were good in 10 patients and satisfactory in another 6 patients . Angiography showed improvement in only one . Twenty patients experienced slight side effects , appearing during the first 10 days , lasting not more than 6 days and subsiding spontaneously . In none of the patients was it necessary to interrupt or discontinue the treatment . In view of these results we consider pyridinolcarbamate indicated in patients with advanced stages of peripheral arterial occlusive disease , when other treatments have failed . The present results do not allow evaluation of Anginine treatment in earlier stages of the disease AIM The aim of this study was to compare the effects of iloprost and lumbar sympathectomy ( LS ) in the treatment of Buerger 's disease . METHODS Two hundred patients with rest pain and /or ischemic ulcers were r and omized to undergo LS or 28-day intravenous treatment of iloprost . The primary endpoint was complete healing without pain or major amputation at 4 and 24 weeks . The secondary endpoints were analgesic requirement , reduction in the ulcer size , 50 % reduction of the ulcer , and shift in the modified SVS/ISCVS clinical status grading scale . RESULTS The comparison was carried out in 162 patients ( iloprost : n=84 ; LS : n=78 ) . Complete healing rate was 61.9 % in the iloprost group , but 41 % in the LS group at the 4th week ( P=0.012 ) ; respective values for the 24th week were 85.3 % , 52.3 % , P<0.001 . Analgesic requirement was lower in the iloprost group at the 4th and 24th weeks ( P=0.01 , and P=0.098 , respectively ) . The size of the ulcers decreased more in the iloprost group than the LS group ( P=0.044 and P=0.035 at 4th and 24th weeks ) ; 50 % reduction in the ulcer size in the iloprost group was greater than in the LS group ( P=0.001 and P=0.009 at 4th and 24th weeks ) . SVS/ISCVS grading scale demonstrated a better clinical benefit in patients treated with iloprost ( P<0.001 at 4th week , and P<0.001 and at 24th week ) . CONCLUSIONS The results of this independent study indicate that using iloprost relieves ischemic symptoms better than LS . In the era of stable prostacyclin analogues , there is no reliable evidence to support the use of LS in Buerger 's disease Background : The mechanism underlying Buerger 's disease ( BD ) is still unknown . Recently , thrombophilic conditions predisposing to a hypercoagulable state have been hypothesized as triggers for BD . The aim of the study is to evaluate the prevalence of the hyperhomocysteinemia and level of the anticardiolipin antibodies , and the role of folic acid on the hyperhomocysteinemia and on the rate of the amputations in the patients with BD . Material s and Methods : In an experimental placebo-controlled double-blinded study , between 2004 and 2010 , thirty patients with BD were r and omly assigned into two groups ( 14 patients in a drug group and 16 patients in the placebo group ) . Drug or placebo was administered , and they were followed in 2 and 6 months for homocysteine , Anticardiolipin antibodies and the risk of amputations . Results : At the beginning of the study homocysteine level was higher than normal in 19 patients ( 63 % ) . There was a significant decrease in homocysteine level during 6 months in folic acid group ( P < 0.001 ) , but there was no change in the placebo group . None of our patients had elevated Anticardiolipin antibodies , and there was no change in the level of Anticardiolipin antibody during study . High level of homocysteine did not associate with more amputations during 6 months of study ( P > 0.05 ) . Conclusion : This study shows the hyperhomocysteinemia in BD , and the benefit of folic acid treatment in homocysteine lowering , but folic acid does n’t inhibit the risk of major and minor amputation during 6 months of follow-up . Longer follow-up may reveal the role of folic acid in these 152 patients with thromboangiitis obliterans ( Buerger 's disease ) and pain from critical leg ischaemia were r and omly allocated to receive iloprost , a chemically stable prostacyclin analogue , or low-dose aspirin , for 28 days in a double-blind trial . On review , 19 patients did not fulfil the stringent entry criteria . Of the other 133 patients , 98 also had leg ulcers . After 21 - 28 days , 58 ( 85 % ) of 68 iloprost-treated patients showed ulcer healing or relief of ischaemic pain , compared with 11 ( 17 % ) of 65 in the aspirin-treated group . 43 ( 63 % ) on iloprost treatment had complete relief of pain , compared with 18 ( 28 % ) on aspirin . Ulcers healed completely in 18 of 52 ( 35 % ) who received iloprost compared with 6 of 46 ( 13 % ) who received aspirin . 6 months after the start of treatment , the response rate was 45 of 51 ( 88 % ) patients treated with iloprost compared with 12 of 44 ( 21 % ) patients treated with aspirin We studied the effects of prostacyclin ( PGI2 ) and its stable analog , iloprost , on blood fibrinolytic activity in 33 patients with peripheral arterial disease . Ten subjects ( group A ) received three 5-hour infusions of iloprost on three consecutive days . The remaining 23 patients received three different 5-hour infusions ( placebo , iloprost 2 ng/kg/min , PGI2 5 ng/kg/min ) . Tissue plasminogen activator ( t-PA ) , total plasma fibrinolytic activity and euglobulin clot lysis time ( ECLT ) were determined in patients before and after each infusion , both in freely flowing blood sample s and following 10 min venous occlusion . In patients of group A , ECLT at rest was significantly shortened after all three iloprost infusions ( on average by about 5 - 11 % ) . First and third infusions produced also shortening of ECLT after venostasis ( by 21 and 32 % ) . Statistically significant rise in t-PA activity ( by about 68 % on average ) accompanied only the first infusion . In patients of the group B iloprost provoked significant fall in ECLT at rest ( by about 19 % on average ) only . PGI2 shortened ECLT both at rest and after venous occlusion ( by about 17 % and 20 % on average , respectively ) and led to a rise in t-PA activity after venous occlusion by about 33 % on average . Our results indicate that prostacyclin and its stable analog , iloprost , enhance fibrinolytic activity in man by releasing or facilitating the release of tissue plasminogen activator from the vessel wall Seven patients ( 5 with arteriosclerosis obliterans and 2 with Buerger 's disease ) completed a two‐phase double‐blind crossover trial of  propranolol in intermittent claudication . Performance was measured on a moving treadmill . In the initial phase , the patients were hospitalized in order to determine an “ effective ” dose of propranolol . Improvement was noted in all : after 1,600 mg in 5 and after 240 mg and 600 mg in the others . The controlled phase was carried out on an outpatient basis over 8 weeks , the patients receiving propranolol and placebo in a r and om manner , each for two 2‐week periods . Comparison of matched periods of drug and placebo revealed no advantage  for propranolol . Patients ’ performances deteriorated with time . None of the patients evidence d deterioration of occlusive peripheral arterial disease that could be attributed to propranolol , in spite of the high doses used 
    Output:
    
When comparing folic acid with placebo in patients with Buerger 's disease and hyperhomocysteinaemia , pain scores were similar , there were no new cases of amputation in either group , and ulcer healing was not assessed ( very low quality evidence ) .Treatment side effects such as headaches , flushing or nausea were not associated with treatment interruptions or more serious consequences .
Moderate quality evidence suggests that intravenous iloprost ( prostacyclin analogue ) is more effective than aspirin for eradicating rest pain and healing ischaemic ulcers in Buerger 's disease , but oral iloprost is not more effective than placebo .
Verylow and low quality evidence suggests there is no difference between prostacyclin ( iloprost and clinprost ) and the prostagl and in analogue alprostadil for healing ulcers and relieving pain respectively in severe Buerger 's disease .
Very-low quality evidence suggests there is no difference in pain scores and amputation rates between folic acid and placebo , in people with Buerger 's disease and hyperhomocysteinaemia .