***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: A double-blind , parallel group , multicenter clinical trial of pentoxifylline compared with placebo enrolled 150 patients with moderately severe chronic occlusive arterial disease ( COAD ) at three centers in Sc and inavia . The study consisted of a 4 - 6 week single-blind , placebo-controlled run-in phase , during which the stabilization of the initial claudication distance of all patients was assessed before r and omization to a 6-month double-blind observation period . The diagnosis of COAD was established by clinical findings , conventional angiography , and noninvasive peripheral Doppler pressure assessment at rest and after exercise . The results of the overall intention-to-treat analysis of the study population show statistically significant superiority of pentoxifylline over placebo for all absolute claudication distance summary and end point measures . By using two clinical ly relevant parameters , which are a resting ankle/arm pressure ratio 0.8 or less and a duration of COAD for greater than 1 year , a target population could be defined in whom trial results became highly significant . For nontarget patients with mild COAD , we conclude that basic therapeutic measures should include the treatment of risk factors and the initiation of physical training . For target patients , however , a multifactorial therapeutic approach , including the use of pentoxifylline , is justified The influence of the xanthine derivative pentoxifylline ( ' Trental ' or BL191 ; Hoechst-Roussel ) on exercise tolerance was measured in 38 subjects with stable , severe to moderately severe , intermittent claudication who completed a r and omised , double-blind , placebo controlled , cross-over clinical trial . Patients received placebo tablets or 400 mg slow-release pentoxifylline tablets ( ' Trental 400 ' ) twice a day for one week , followed by three times daily for seven weeks , and then crossed over to receive the alternate preparation for another eight weeks . Claudication distance and walking distance were measured on a treadmill before starting treatment and again at four-week intervals during the trial . At the same times , red blood cell filterability , plasma fibrinogen concentration and blood viscosity , resting and post-ischemic calf muscle blood flow , and the resting and post-exercise ankle/brachial systolic pressure ratio were also measured . In this study , the observed effects of  pentoxifylline treatment were no greater than those of placebo , even though serum levels of pentoxifylline and its hydroxy-metabolite were within the anticipated range . This was shown by a ' therapeutic effect ratio ' of 0.98 for treadmill claudication distance and 0.96 for treadmill walking distance after within-patient analysis at the end of the cross-over ( where a ratio of 1.0 means the test drug and placebo effects are identical ) . These ratios have 95 % confidence limits of 0.72 - 1.34 and 0.74 - 1.25 , respectively In a r and omized open study , the combination of either prostagl and in E1 ( PGE1 ) or pentoxifylline with controlled vascular training was compared with vascular training alone in patients with peripheral arterial occlusive disease in stage IIb . Forty-four patients were r and omly assigned to treatment either of intensive vascular training alone ( n = 15 ) or in combination with either i.v . pentoxifylline ( 200 mg over 2 hours BID , n = 15 ) or PGE1 ( 40 micrograms over 2 hours BID , n = 14 ) . The basic therapy was a well-defined routine for vascular training , which was identical for all groups . The duration of therapy was 4 weeks . In all three test groups , there was a significant increase in the walking distance . There was a 119 % increase in symptom-free walking distance in the exercise-only group . In comparison with exercise alone , the additional administration of pentoxifylline produced no greater effect ; the increase was 105 % . In contrast , administration of PGE1 combined with exercise achieved a remarkable improvement of 604 % . Between-group comparison revealed the significant superiority of treatment with PGE1 ( P < .05 ) . During the 1-year follow-up , there was a reduction in the walking performance in all groups , albeit of variable extent . In the exercise-only and the pentoxifylline groups , the maintained increase in walking distance was only 30 % compared with baseline values before the beginning of therapy . In the PGE1 group , on the other h and , the maintained improvement was 149 % . Nine of 14 patients were still in stage IIa of peripheral arterial occlusive disease 1 year after PGE1 therapy The efficacy , safety , and tolerance of pentoxifylline ( Trental , Hoechst-Roussel Pharmaceuticals , Inc. ) in the treatment of intermittent claudication associated with chronic occlusive arterial disease ( COAD ) were evaluated in a double-blind , placebo-controlled , parallel-group , multicenter clinical trial involving a total of 128 out patients . The response to treatment was ascertained at regular intervals during the trial by measuring the distance walked prior to the onset of claudication when patients were subjected to a st and ardized treadmill test . Pentoxifylline given orally in doses up to 1200 mg/day was significantly more effective than placebo in increasing both the initial and absolute claudication distances in patients with COAD . Reduction of lower limb paresthesias also suggested greater clinical improvement in the pentoxifylline treated patients . These results support the hypothesis that pentoxifylline reduces blood viscosity by improving red cell flexibility , and thereby enhances blood flow in patients with COAD . White the precise mode of therapeutic action requires clarification , pentoxifylline was well tolerated with minimal unwanted effects A multicenter , prospect i ve , pla cebo-controlled , double-blind trial was conducted to investigate the effi cacy of intravenous infusion therapy with pentoxifylline over fourteen days in patients suffering from angio graphically confirmed chronic pe ripheral occlusive arterial disease , Fontaine stage II , with at least a six- month history . After a washout phase of one week , the patients received in accordance with a r and omization scheme either an i.v . infusion of 300 mg of pentoxifylline ( 15 mL am poules ) or 15 mL of a 0.9 % NaCl so lution in 250 mL of 5 % laevulose , administered over three hours twice daily . The main efficacy parameters were treadmill-assessed initial claudi cation distance ( ICD ) and absolute claudication distance ( ACD ) . Base line testing revealed a mean ICD of 131 m in the pentoxifylline group and 126 m in the placebo cohort ; mean ACD values were 239 m and 225 m respectively . The group of patients treated with pentoxifylline ( n=75 ) displayed a significantly greater i m provement ( p < 0.0001 ) in ICD ( + 70 % ) and ACD ( + 60 % ) than the placebo group did ( + 33 % and 32 % , respectively ) ( n=79 ) . The infusions were well tolerated in both groups The efficacy of pentoxifylline ( PXF ) in severe intermittent claudication was studied comparing PXF and placebo . Patients were r and omized into two treatment plans : PXF ( 2400 mg , four 600-mg tablets daily ) or equivalent placebo was administered for 10 days . The exercise protocol associated with treatment was conducted under supervision . Skin flux ( RF ) was measured at rest and after 1 minute of exercise ( AEF = after exercise flux ; 3 km/hr , 12 % inclination ) with laser Doppler . PO2 and PCO2 were measured at the dorsum of the foot . All 20 included patients completed the study . The two groups were comparable . In the PXF group there was a significant increase in RF , AEF , and in PO2 ( p<0.05 ) ; PCO2 was decreased ( p<0.05 ) . There were also changes in the placebo group , significantly lower than those observed in the PXF group ( p<0.05 ) . In conclusion high-dose PXF treatments improved all microcirculatory parameters in subjects with short-range claudication even with a short period of treatment The effects of a five-week course of haemodilution or pentoxifylline were compared in two matched groups of 10 patients each ( 18 men , 2 women ; mean age 63 [ 47 - 77 ] years ) with peripheral vascular disease of the legs , using clinical findings and Doppler ultrasound measurements as the criteria . Ten patients ( group I ) had six venesections of 400 ml each followed by the injection of 500 ml low-molecular dextran ( 10 % ) , while the other ten ( group II ) received 400 mg pentoxifylline four times daily by mouth after initial intravenous loading . Pain-free and maximal walking distance increased in group I by 139 and 598 m , respectively ( P less than 0.01 ) , and by 155 ( P less than 0.01 ) and 191 m in group II . The greater increase in maximal walking distance in group I was significant as calculated by regression analysis ( P less than 0.05 ) . Only in group I was there a significant prestenotic maximal and effective increase in blood flow velocity ( by 66 % : P less than 0.001 and 68 % : P less than 0.05 , respectively ) , while the poststenotic effective velocity also increased significantly by 66 % ( P less than 0.01 ) . There was no significant change in group II patients The LONFLIT1 and 2 studies established that in high-risk subjects after long ( > 10 hours ) flights , the incidence of deep venous thrombosis ( DVT ) may be between 4 % and 6 % . The LONFLIT3 study aim ed to evaluate methods of prevention in high-risk subjects . Of 467 subjects contacted for the study , 300 were included . These 300 subjects at high risk for DVT were r and omized , after informed consent , into three groups : 1 ) a control group that had no prophylaxis ; 2 ) an aspirin treatment group , in which patients were treated with 400 mg , ( tablets of oral , soluble aspirin ; one dose daily for 3 days , starting 12 hours before the beginning of the flight ) ; and 3 ) a low-molecular-weight heparin ( LMWH ) group , in which one dose of enoxaparine was injected between 2 and 4 hours before the flight . The dose was weight-adjusted ( 1000 IU [ equivalent to 0.1 mL ] per 10 kg of body weight ) . Subjects with potential problems due to prophylaxis with aspirin or LMWH or at risk of drug interactions were excluded . Of the 100 included subjects in each group , a total of 249 subjects completed the study ( dropouts due to low compliance or traveling/connections problems were 17 % ) . Age and sex distribution were comparable in the three groups as well as risk distributions . Mean age was 47 ( range , 28 - 75 ; SD , 11 ; 65 % males ) . Of the 82 subjects in the control group , there were 4.82 % of subjects with DVT with two superficial thromboses . In total 4.8 % of limbs suffered a thrombotic event . Of 84 subjects in the aspirin treatment group , there were 3.6 % of patients with DVT and three superficial thrombosis . In total 3.6 % of limbs had a throm botic event . In the LMWH group ( 82 subjects ) , there were no cases of DVT . One superficial thrombosis was documented . In total only 0.6 % of limbs had a thrombotic event ( p < 0.002 in comparison with the other two groups ) . DVT was asymptomatic in 60 % of subjects ; 85 % of DVTs were observed in passengers in non-aisle seats . Mild gastrointestinal symptoms were reported in 13 % of patients taking aspirin . One dose of LMWH is an important option to consider in high-risk subjects during long-haul flights Peripheral artery disease is associated with altered blood rheologic properties , including increased viscosity and decreased red blood cell ( RBC ) deformability . Pentoxifylline and cilostazol are available therapies for intermittent claudication . Improvement of blood viscosity and erythrocyte deformability have been cited as potential mechanisms of action for pentox ifylline . Cilostazol is a new drug with antiplatelet and vasodilating activity , but the mechanism by which it promotes an improvement in walking is not known . This study was performed to evaluate and compare the hemorheologic effects of pentoxifylline and cilostazol on viscosity , fibrinogen levels , and erythrocyte deformability when administered to adults with moderate to severe claudication . A double-blind , controlled study was conducted and included 59 patients ( 46 male , 13 female ; mean age 65 yr ) r and omized to pentoxifylline 400 mg orally thrice daily ( n=20 ) , cilostazol 100 mg orally twice daily ( n=19 ) , or placebo ( n=20 ) ; all subjects were observed for 24 weeks . Walking ability was assessed before , during , and at the conclusion of treatment by st and ard constant speed , variable grade treadmill testing . Erythrocyte deforma bility was measured by passage of washed RBCs , 10 % hematocrit in phosphate buffered saline ( PBS ) , through a polycarbonate membrane with 4.7 to 5.0 μm pores . Whole blood and plasma viscos 
    Output:
    
Most included studies suggested improvement in PFWD and TWD for pentoxifylline over placebo and other treatments , but the statistical and clinical significance of findings from individual trials is unclear .
Pentoxifylline generally was well tolerated ; the most commonly reported side effects consisted of gastrointestinal symptoms such as nausea .
AUTHORS ' CONCLUSIONS Given the generally poor quality of published studies and the large degree of heterogeneity evident in interventions and in results , the overall benefit of pentoxifylline for patients with Fontaine class II intermittent claudication remains uncertain .
Pentoxifylline was shown to be generally well tolerated .
Based on total available evidence , high- quality data are currently insufficient to reveal the benefits of pentoxifylline for intermittent claudication