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: A double-blind controlled clinical trial has shown no benefit from the use of sulphadoxine-pyrimethamine over a 12-month period in chronically active Crohn ’s disease A mycobacterial infection may be the cause of Crohn ’s disease in some patients . Measurement of intestinal permeability may identify Crohn ’s disease patients with a high likelihood of relapse and may quantify the severity of intestinal injury One hundred and thirty patients with active symptoms of Crohn 's disease were treated in a double blind r and omised controlled trial with rifampicin , isoniazid , and ethambutol , or identical placebos for up to two years . All other treatment considered necessary was continued . Analyses were based on 126 patients , 63 in each treatment group . Thirty seven in the active and 30 in the placebo group had previous surgical procedures . There was no difference in concomitant treatment between the two groups . Thirty in the active and 46 in the placebo groups were taking corticosteroids at entry to the trial . Forty eight of 63 patients in the active and 49 of 63 in the placebo group , completed at least 12 months ' therapy . Reasons for early withdrawal included pregnancy , adverse reaction , and failure to comply . There was no significant difference in the mean number of months completed between the two groups . Nineteen adverse reactions were recorded for 17 patients in the active group compared with three reactions in patients on placebo . All of the nine patients withdrawn early because of adverse reactions were in the active group . Fifteen patients on active treatment and 14 on placebo had surgery during the trial with no difference in the type of surgery required between the groups . Radiological assessment s based on 98 patients at the end of the trial showed no significant differences between groups in changes of extent of disease . More patients developed strictures on placebo compared with active treatment but without a statistically significant difference . No differences were found between groups for the total prednisolone dose or the number of days on which prednisolone dose was 10 mg or above . Serial measurements of body weight and Crohn 's disease activity index ( CDAI ) together with blood values for albumin , haemoglobin , white cell count , and platelets showed no consistent different differences between groups . There were occasional significant differences for some of these values between groups , which were not sustained . The trail provides little evidence of tangible benefit from the trail treatment Fifty-two patients with severe Crohn 's disease were enrolled in this study . Six ( 11.5 % ) were intolerant of the medication and had to be excluded . The remaining 46 patients were treated with rifabutin in combination with a macrolide antibiotic ( clarithromycin or azithromycin ) .  Patients were treated for a mean of 18.7 ( range 6 - 35 ) months and followed up for 25.1 ( range 7 - 41 ) months . Of the 19 patients who were steroid dependent at the start of this study , only two continued to require steroids when treatment was established . A reduction in the Harvey-Bradshaw Crohn 's disease activity index occurred after 6 months ' treatment ( P = 0.004 , paired Wilcoxon test ) and was maintained at 24 months ( P < 0.001 ) . An improvement in inflammatory parameters was observed as measured by a reduction in erythrocyte sedimentation rate ( P = 0.009 ) and C-reactive protein ( P = 0.03 ) at 18 months compared with pretreatment levels , and an increase in serum albumin at 12 months ( P = 0.04 ) . When subsets of the study population were analysed , patients with pan-intestinal disease achieved better remission at 2 years than did those with less extensive involvement ( P = 0.04 , Mann-Whitney U-test ) . No difference in treatment response by age , disease duration , the presence of granulomas on histology , or the occurrence of drug-induced side-effects , was observed . These data suggest that treatment with rifabutin and clarithromycin or azithromycin may result in a substantial clinical improvement in Crohn 's disease and justify the conduct of a r and omized controlled trial BACKGROUND & AIMS Mycobacterium avium subspecies paratuberculosis has been proposed as a cause of Crohn 's disease . We report a prospect i ve , parallel , placebo-controlled , double-blind , r and omized trial of 2 years of clarithromycin , rifabutin , and clofazimine in active Crohn 's disease , with a further year of follow-up . METHODS Two hundred thirteen patients were r and omized to clarithromycin 750 mg/day , rifabutin 450 mg/day , clofazimine 50 mg/day or placebo  , in addition to a 16-week tapering course of prednisolone . Those in remission ( Crohn 's Disease Activity Index < or=150 ) at week 16 continued their study medications in the maintenance phase of the trial . Primary end points were the proportion of patients experiencing at least 1 relapse at 12 , 24 , and 36 months . RESULTS At week 16 , there were significantly more subjects in remission in the antibiotic arm ( 66 % ) than the placebo arm ( 50 % ; P=.02 ) . Of 122 subjects entering the maintenance phase , 39 % taking antibiotics experienced at least 1 relapse between weeks 16 and 52 , compared with 56 % taking placebo ( P=.054 ) . At week 104 , the figures were 26 % and 43 % , respectively ( P=.14 ) . During the following year , 59 % of the antibiotic group and 50 % of the placebo group relapsed ( P=.54 ) . CONCLUSIONS Using combination antibiotic therapy with clarithromycin , rifabutin , and clofazimine for up to 2 years , we did not find evidence of a sustained benefit . This finding does not support a significant role for Mycobacterium avium subspecies paratuberculosis in the pathogenesis of Crohn 's disease in the majority of patients . Short-term improvement was seen when this combination was added to corticosteroids , most likely because of nonspecific antibacterial effects We pursued the possibility that Mycobacterium kansasii might be an aetiological agent in Crohn 's disease by carrying out a trial of treatment with antimycobacterial drugs .  Twenty seven patients with Crohn 's disease took part in a two year r and omised double blind , crossover , controlled trial of rifampicin plus ethambutol against placebo .  Fourteen patients completed the trial ; four required an operation ; five were withdrawn as poor compliers , and four because of adverse effects . There was no significant difference in response to the active drugs compared with placebo when expressed in terms of a Crohn 's disease activity index or any clinical indicator of disease activity . There was no suggestion that any subgroup of patients - for example , different regions of bowel affected or previous operation - were favourably affected by the drugs . There was no consistent pattern of change in  prednisolone requirements although eight patients on long term sulphasalazine had a significant reduction in their plasma sulphapyridine concentrations during the active treatment period . A significant reduction in total white blood count and an increase in plasma ALT were seen during active therapy . The results of the study do not suggest that rifampicin and ethambutol have a role to play in the treatment of Crohn 's disease UNLABELLED Several recent reports have suggested an association of atypical mycobacteria with Crohn 's disease . OBJECTIVES The goal of this double-blind , placebo-controlled trial was to determine the efficacy of treatment with antimycobacterial drugs in maintaining clinical remission and in reducing active inflammatory lesions . METHODS Forty patients ( 15 male ) with refractory , steroid-dependent Crohn 's disease were r and omized to receive 2 months of tapering steroids plus either a 9-month regimen of ethambutol , clofazimine , dapsone and 1-day dose only of rifampicin ( n = 22 ) , or identical placebo . RESULTS Three patients ( two on active drug ) were unable to discontinue steroids , and one patient on active drug was withdrawn for side effects during the first 2 months . Three of the remaining 19 patients on active drug relapsed during the study period , compared with 11 of 17 on placebo ( log likelihood ratio = 4.6 ; p = 0.03 ) . Another patient was withdrawn in remission at 5 months for anemia related to dapsone . Nine patients whose disease relapsed or persisted on placebo were crossed over to active drug ; five achieved sustained remission , two failed , and two were withdrawn for side effects . Substantial endoscopic or radiologic healing did not occur . CONCLUSION This study suggests that the treatment regimen with rifampicin , ethambutol , clofazimine , and dapsone is effective in relief of symptoms and maintenance of remission in some Crohn 's disease patients Background : Recent studies indicate that persistent intestinal inflammation in patients with Crohn 's disease ( CD ) might be caused by abnormal intestinal microbiota . This hypothesis may suggest a beneficial effect of antibiotics in CD therapy . So far , guidelines do not recommend antibiotics except in the treatment of complicated CD , and there are few studies on the effects of rifaximin in these patients . Methods : Between December 2011 and December 2012 , we performed a blinded r and omized trial in 168 patients with a previous history of moderately active CD concerning the efficacy of rifaximin .  All the patients had previously achieved remission with st and ard therapy ( prednisone/budesonide ) . Data from patients receiving 800 mg of rifaximin ( 83 patients ) twice a day for 12 weeks were compared with those from patients who received placebo ( 83 patients ) . The primary endpoint was maintaining remission during the follow-up . Results : All the patients ( 100 % ; 83/83 ) on 800 mg of rifaximin were in remission after 12 weeks of treatment in comparison with 84 % ( 70/83 ) of the placebo group . This significant difference was also persistent at the 24-week follow-up [ 78 % ( 65/83 ) vs. 41 % ( 34/83 ) , respectively ] . The last evaluation performed at 48 weeks revealed disease activity in 45 % ( 38/83 ) of the patients of the rifaximin group , i.e. a significant decrease compared with the placebo group [ 75 % ( 63 of 83 ) ] . Conclusions : Remission previously obtained with st and ard treatment can be sustained in patients with moderately active CD after the administration of 800 mg of rifaximin BACKGROUND AND AIM The pathogenesis of Crohn 's disease is unclear , but many studies suggest that luminal bacteria play an important role in chronic intestinal inflammation in patients with this condition . Clarithromycin is a macrolide antibiotic with immunomodulatory activity . The aim of this study was to evaluate the effect of clarithromycin therapy in Japanese patients with Crohn 's disease . METHODS Fourteen patients with active Crohn 's disease ( 12 with ileocolonic , one with colonic , one with small bowel type ) were treated with oral clarithromycin 200 mg twice daily for 4 weeks . Patients who showed a clinical response within 4 weeks continued the therapy for up to 24 weeks . Four patients also received azathioprine . Clinical activity was assessed with the Crohn 's Disease Activity Index ( CDAI ) at entry and at 4 , 12 , and 24 weeks after starting clarithromycin . RESULTS The mean CDAI score at entry was 343.5 . Within 4 weeks , eight ( 57.1 % ) of the 14 patients showed clinical improvement , and five ( 35.7 % ) of the eight patients achieved remission . All of those eight patients continued clarithromycin therapy after 4 weeks , and six ( 42.9 % ) were in clinical remission at 12 weeks . Of the 14 total patients , four ( 28.6 % ) continued clarithromycin for more than 24 weeks , and have remained in remission . Patients who received azathioprine concomitantly had a better response to clarithromycin therapy . No severe side-effects were observed during the study period . CONCLUSIONS This open label study showed encouraging results of clarithromycin therapy in Japanese patients with active Crohn 's disease Crohn ’s disease seems likely to be due in some way to bacteria . Clarithromycin is a broad spectrum macrolide antibiotic with good penetration into macrophages and may be effective in eradicating the organisms that are presumed to be at the centre of the granulomatous reaction in Crohn ’s disease In order to study the effect of clofazimine , a powerful antimycobacterial and antiinflammatory agent , 49 patients with active Crohn 's disease were r and omized to either corticosteroids plus clofazimine 100 mg daily ( N=25 ) or to steroids and matching placebo ( N=24 ) . A total of 28 patients ( 58 % ) went into disease remission ( clofazimine 16 , placebo 12;P = NS ) with a fall in disease activity score from 10.5±4.4 to 3.3±3.5 . Patients were treated for a further eight months with clofazimine or placebo and 18 of 28 maintained their remission and completed the study ( clofazimine 12 , placebo 6;P = NS ) . Side effects were minor and consisted of skin rash and increased pigmentation  . Clofazimine as a solitary antimycobacterial agent appears ineffective in inducing remission in Crohn 's disease but may have a role in either disease maintenance or combination chemotherapy OBJECTIVES Bacteria in the gut lumen may play a role in the 
    Output:
    
agent
***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 controlled clinical trial has shown no benefit from the use of sulphadoxine-pyrimethamine over a 12-month period in chronically active Crohn ’s disease A mycobacterial infection may be the cause of Crohn ’s disease in some patients . Measurement of intestinal permeability may identify Crohn ’s disease patients with a high likelihood of relapse and may quantify the severity of intestinal injury One hundred and thirty patients with active symptoms of Crohn 's disease were treated in a double blind r and omised controlled trial with rifampicin , isoniazid , and ethambutol , or identical placebos for up to two years . All other treatment considered necessary was continued . Analyses were based on 126 patients , 63 in each treatment group . Thirty seven in the active and 30 in the placebo group had previous surgical procedures . There was no difference in concomitant treatment between the two groups . Thirty in the active and 46 in the placebo groups were taking corticosteroids at entry to the trial . Forty eight of 63 patients in the active and 49 of 63 in the placebo group , completed at least 12 months ' therapy . Reasons for early withdrawal included pregnancy , adverse reaction , and failure to comply . There was no significant difference in the mean number of months completed between the two groups . Nineteen adverse reactions were recorded for 17 patients in the active group compared with three reactions in patients on placebo . All of the nine patients withdrawn early because of adverse reactions were in the active group . Fifteen patients on active treatment and 14 on placebo had surgery during the trial with no difference in the type of surgery required between the groups . Radiological assessment s based on 98 patients at the end of the trial showed no significant differences between groups in changes of extent of disease . More patients developed strictures on placebo compared with active treatment but without a statistically significant difference . No differences were found between groups for the total prednisolone dose or the number of days on which prednisolone dose was 10 mg or above . Serial measurements of body weight and Crohn 's disease activity index ( CDAI ) together with blood values for albumin , haemoglobin , white cell count , and platelets showed no consistent different differences between groups . There were occasional significant differences for some of these values between groups , which were not sustained . The trail provides little evidence of tangible benefit from the trail treatment Fifty-two patients with severe Crohn 's disease were enrolled in this study . Six ( 11.5 % ) were intolerant of the medication and had to be excluded . The remaining 46 patients were treated with rifabutin in combination with a macrolide antibiotic ( clarithromycin or azithromycin ) .  Patients were treated for a mean of 18.7 ( range 6 - 35 ) months and followed up for 25.1 ( range 7 - 41 ) months . Of the 19 patients who were steroid dependent at the start of this study , only two continued to require steroids when treatment was established . A reduction in the Harvey-Bradshaw Crohn 's disease activity index occurred after 6 months ' treatment ( P = 0.004 , paired Wilcoxon test ) and was maintained at 24 months ( P < 0.001 ) . An improvement in inflammatory parameters was observed as measured by a reduction in erythrocyte sedimentation rate ( P = 0.009 ) and C-reactive protein ( P = 0.03 ) at 18 months compared with pretreatment levels , and an increase in serum albumin at 12 months ( P = 0.04 ) . When subsets of the study population were analysed , patients with pan-intestinal disease achieved better remission at 2 years than did those with less extensive involvement ( P = 0.04 , Mann-Whitney U-test ) . No difference in treatment response by age , disease duration , the presence of granulomas on histology , or the occurrence of drug-induced side-effects , was observed . These data suggest that treatment with rifabutin and clarithromycin or azithromycin may result in a substantial clinical improvement in Crohn 's disease and justify the conduct of a r and omized controlled trial BACKGROUND & AIMS Mycobacterium avium subspecies paratuberculosis has been proposed as a cause of Crohn 's disease . We report a prospect i ve , parallel , placebo-controlled , double-blind , r and omized trial of 2 years of clarithromycin , rifabutin , and clofazimine in active Crohn 's disease , with a further year of follow-up . METHODS Two hundred thirteen patients were r and omized to clarithromycin 750 mg/day , rifabutin 450 mg/day , clofazimine 50 mg/day or placebo  , in addition to a 16-week tapering course of prednisolone . Those in remission ( Crohn 's Disease Activity Index < or=150 ) at week 16 continued their study medications in the maintenance phase of the trial . Primary end points were the proportion of patients experiencing at least 1 relapse at 12 , 24 , and 36 months . RESULTS At week 16 , there were significantly more subjects in remission in the antibiotic arm ( 66 % ) than the placebo arm ( 50 % ; P=.02 ) . Of 122 subjects entering the maintenance phase , 39 % taking antibiotics experienced at least 1 relapse between weeks 16 and 52 , compared with 56 % taking placebo ( P=.054 ) . At week 104 , the figures were 26 % and 43 % , respectively ( P=.14 ) . During the following year , 59 % of the antibiotic group and 50 % of the placebo group relapsed ( P=.54 ) . CONCLUSIONS Using combination antibiotic therapy with clarithromycin , rifabutin , and clofazimine for up to 2 years , we did not find evidence of a sustained benefit . This finding does not support a significant role for Mycobacterium avium subspecies paratuberculosis in the pathogenesis of Crohn 's disease in the majority of patients . Short-term improvement was seen when this combination was added to corticosteroids , most likely because of nonspecific antibacterial effects We pursued the possibility that Mycobacterium kansasii might be an aetiological agent in Crohn 's disease by carrying out a trial of treatment with antimycobacterial drugs .  Twenty seven patients with Crohn 's disease took part in a two year r and omised double blind , crossover , controlled trial of rifampicin plus ethambutol against placebo .  Fourteen patients completed the trial ; four required an operation ; five were withdrawn as poor compliers , and four because of adverse effects . There was no significant difference in response to the active drugs compared with placebo when expressed in terms of a Crohn 's disease activity index or any clinical indicator of disease activity . There was no suggestion that any subgroup of patients - for example , different regions of bowel affected or previous operation - were favourably affected by the drugs . There was no consistent pattern of change in  prednisolone requirements although eight patients on long term sulphasalazine had a significant reduction in their plasma sulphapyridine concentrations during the active treatment period . A significant reduction in total white blood count and an increase in plasma ALT were seen during active therapy . The results of the study do not suggest that rifampicin and ethambutol have a role to play in the treatment of Crohn 's disease UNLABELLED Several recent reports have suggested an association of atypical mycobacteria with Crohn 's disease . OBJECTIVES The goal of this double-blind , placebo-controlled trial was to determine the efficacy of treatment with antimycobacterial drugs in maintaining clinical remission and in reducing active inflammatory lesions . METHODS Forty patients ( 15 male ) with refractory , steroid-dependent Crohn 's disease were r and omized to receive 2 months of tapering steroids plus either a 9-month regimen of ethambutol , clofazimine , dapsone and 1-day dose only of rifampicin ( n = 22 ) , or identical placebo . RESULTS Three patients ( two on active drug ) were unable to discontinue steroids , and one patient on active drug was withdrawn for side effects during the first 2 months . Three of the remaining 19 patients on active drug relapsed during the study period , compared with 11 of 17 on placebo ( log likelihood ratio = 4.6 ; p = 0.03 ) . Another patient was withdrawn in remission at 5 months for anemia related to dapsone . Nine patients whose disease relapsed or persisted on placebo were crossed over to active drug ; five achieved sustained remission , two failed , and two were withdrawn for side effects . Substantial endoscopic or radiologic healing did not occur . CONCLUSION This study suggests that the treatment regimen with rifampicin , ethambutol , clofazimine , and dapsone is effective in relief of symptoms and maintenance of remission in some Crohn 's disease patients Background : Recent studies indicate that persistent intestinal inflammation in patients with Crohn 's disease ( CD ) might be caused by abnormal intestinal microbiota . This hypothesis may suggest a beneficial effect of antibiotics in CD therapy . So far , guidelines do not recommend antibiotics except in the treatment of complicated CD , and there are few studies on the effects of rifaximin in these patients . Methods : Between December 2011 and December 2012 , we performed a blinded r and omized trial in 168 patients with a previous history of moderately active CD concerning the efficacy of rifaximin .  All the patients had previously achieved remission with st and ard therapy ( prednisone/budesonide ) . Data from patients receiving 800 mg of rifaximin ( 83 patients ) twice a day for 12 weeks were compared with those from patients who received placebo ( 83 patients ) . The primary endpoint was maintaining remission during the follow-up . Results : All the patients ( 100 % ; 83/83 ) on 800 mg of rifaximin were in remission after 12 weeks of treatment in comparison with 84 % ( 70/83 ) of the placebo group . This significant difference was also persistent at the 24-week follow-up [ 78 % ( 65/83 ) vs. 41 % ( 34/83 ) , respectively ] . The last evaluation performed at 48 weeks revealed disease activity in 45 % ( 38/83 ) of the patients of the rifaximin group , i.e. a significant decrease compared with the placebo group [ 75 % ( 63 of 83 ) ] . Conclusions : Remission previously obtained with st and ard treatment can be sustained in patients with moderately active CD after the administration of 800 mg of rifaximin BACKGROUND AND AIM The pathogenesis of Crohn 's disease is unclear , but many studies suggest that luminal bacteria play an important role in chronic intestinal inflammation in patients with this condition . Clarithromycin is a macrolide antibiotic with immunomodulatory activity . The aim of this study was to evaluate the effect of clarithromycin therapy in Japanese patients with Crohn 's disease . METHODS Fourteen patients with active Crohn 's disease ( 12 with ileocolonic , one with colonic , one with small bowel type ) were treated with oral clarithromycin 200 mg twice daily for 4 weeks . Patients who showed a clinical response within 4 weeks continued the therapy for up to 24 weeks . Four patients also received azathioprine . Clinical activity was assessed with the Crohn 's Disease Activity Index ( CDAI ) at entry and at 4 , 12 , and 24 weeks after starting clarithromycin . RESULTS The mean CDAI score at entry was 343.5 . Within 4 weeks , eight ( 57.1 % ) of the 14 patients showed clinical improvement , and five ( 35.7 % ) of the eight patients achieved remission . All of those eight patients continued clarithromycin therapy after 4 weeks , and six ( 42.9 % ) were in clinical remission at 12 weeks . Of the 14 total patients , four ( 28.6 % ) continued clarithromycin for more than 24 weeks , and have remained in remission . Patients who received azathioprine concomitantly had a better response to clarithromycin therapy . No severe side-effects were observed during the study period . CONCLUSIONS This open label study showed encouraging results of clarithromycin therapy in Japanese patients with active Crohn 's disease Crohn ’s disease seems likely to be due in some way to bacteria . Clarithromycin is a broad spectrum macrolide antibiotic with good penetration into macrophages and may be effective in eradicating the organisms that are presumed to be at the centre of the granulomatous reaction in Crohn ’s disease In order to study the effect of clofazimine , a powerful antimycobacterial and antiinflammatory agent , 49 patients with active Crohn 's disease were r and omized to either corticosteroids plus clofazimine 100 mg daily ( N=25 ) or to steroids and matching placebo ( N=24 ) . A total of 28 patients ( 58 % ) went into disease remission ( clofazimine 16 , placebo 12;P = NS ) with a fall in disease activity score from 10.5±4.4 to 3.3±3.5 . Patients were treated for a further eight months with clofazimine or placebo and 18 of 28 maintained their remission and completed the study ( clofazimine 12 , placebo 6;P = NS ) . Side effects were minor and consisted of skin rash and increased pigmentation  . Clofazimine as a solitary antimycobacterial agent appears ineffective in inducing remission in Crohn 's disease but may have a role in either disease maintenance or combination chemotherapy OBJECTIVES Bacteria in the gut lumen may play a role in the 
    Output:
    