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: We r and omly assigned 71 patients with active chronic Crohn 's disease who were resistant to or intolerant of corticosteroids to treatment with oral cyclosporine ( 5 to 7.5 mg per kilogram of body weight per day ) or placebo for three months . Disease activity was assessed on a clinical grading scale without knowledge of the treatment given . At the end of the treatment period , 22 of the 37 cyclosporine-treated patients ( 59 percent ) had improvement , as compared with 11 of the 34 placebo-treated patients ( 32 percent ) ( P = 0.032 ) . During cyclosporine treatment , there was significant improvement in plasma orosomucoid levels ( P = 0.0025 ) and the Crohn 's Disease Activity Index ( P = 0.00012 ) . The effect of treatment became evident after two weeks . In the subsequent three months , during which the patients were gradually withdrawn from treatment , the improvement continued in 14 of the 37 patients ( 38 percent ) in the cyclosporine group and in 5 of the 34 ( 15 percent ) in the placebo group ( P = 0.034 ) . No serious adverse events were observed . We conclude that cyclosporine has a beneficial therapeutic effect in patients with active chronic Crohn 's disease and resistance to or intolerance of corticosteroids The effect of azathioprine in patients with active Crohn 's disease has been evaluated in a double-blind cross-over trial . Fifteen patients were treated with both azathioprine and placebo : only two improved while on azathioprine , six got worse , and in seven there was no change . The drug seemed to be the cause of deterioration in two of the patients . Although the drug may be of some value in a few patients , it should be used with caution and only when other measures have failed BACKGROUND & AIMS Uncontrolled studies have suggested that methotrexate may be effective in patients with active ulcerative colitis . The aim of this study was to evaluate the effectiveness of oral methotrexate in chronic steroid-dependent ulcerative colitis in a r and omized , double-blind multicenter trial . METHODS Patients with active ulcerative colitis who have received steroids and /or immunosuppressives for at least 4 months during the preceding 12 months with a current Mayo Clinic score of > or = 7 were included in the study .  Methotrexate ( 12.5 mg ) or placebo was added to their treatment once weekly for 9 months . RESULTS Sixty-seven patients were included ( methotrexate , 30 patients , placebo , 37 patients ) . The proportion of patients entering first remission  ( methotrexate , 46.7 % ; placebo , 48.6 % ) , the time to reach first remission  ( methotrexate , 4.1 + /- 1.9 months ; placebo , 3.4 + /- 1.7 months ) , as well as the proportions of patients having a relapse after first remission  ( methotrexate , 64.3 % ; placebo , 44.4 % ) were not significantly different between the two groups . The mean Mayo Clinic score , the mean monthly steroid dose , and the proportion of abnormal laboratory results during the study were also similar . CONCLUSIONS Methotrexate at a weekly oral dose of 12.5 mg was not found to be better than placebo in the induction or maintenance of remission in patients with chronic active ulcerative colitis AIM : To prospect ively evaluate whether a relationship between thiopurine methyltransferase ( TPMT ) activity and incidence of adverse effects ( especially myelotoxicity ) exists , in a long-term follow-up study of a large group of patients with inflammatory bowel disease treated with azathioprine .  METHODS : TPMT activity in red blood cells ( RBC ) was measured by a radiochemical method in 394 consecutive patients with Crohn 's disease ( 238 ) or ulcerative colitis ( 156 ) starting treatment with azathioprine .  The relationship among several variables and TPMT values was assessed , and the correlation between such levels and the incidence of adverse effects was evaluated . RESULTS : Mean TPMT value was 18.6 ± 4 U/mL RBCs ( range 9.4–33.7 ) . No patient had low levels ( < 5 ) , 7.1 % had intermediate levels ( 5–13.7 ) , and 92.9 % had high levels ( > 13.8 ) . Differences ( P < 0.001 ) were demonstrated in TPMT activity depending on the type of inflammatory bowel disease , but not on the remaining variables ( including treatment with 5-aminosalycilates ) . Adverse effects were reported in 74 patients ( 18.8 % ) , the most frequent being gastrointestinal intolerance ( 9.1 % ) and myelotoxicity ( 4.3 % ) . No patient having adverse effects had low TPMT levels . However , mean TPMT activity was lower in those with adverse effects ( 16.6 ± 3 vs 19.1 ± 4 U/mL , P < 0.001 ) . Moreover , the probability of suffering myelotoxicity in the high TPMT group was only 3.5 % , compared with 14.3 % in the TPMT intermediate group ( 95 % CI = 1.37–14.9 ; OR = 4.5 ) . CONCLUSIONS : The strategy of determining TPMT activity in all patients prior to initiating treatment with azathioprine could help to minimize the risk of myelotoxicity , as patients with intermediate TPMT activity had fourfold more risk than high TPMT activity patients BACKGROUND / AIMS Immunosuppression with methotrexate may be useful in the treatment of Crohn 's disease . We tested the efficacy of methotrexate in refractory Crohn 's disease in a r and omized , controlled trial . METHODOLOGY R and omized , double-blind placebo-controlled trial of methotrexate in 33 patients with steroid-dependent Crohn 's disease , 33 % of whom had previously failed therapy with 6-mercaptopurine .  Patients were given placebo or oral methotrexate 15 mg/week , or adjusted up to 22.5 mg/week , for up to 1 year or until treatment failure . Outcome was assessed by reduction in prednisone dosage , Crohn 's Disease Activity Index , hospital admission , and laboratory parameters . RESULTS Four patients were dropped from the study for non-compliance and one because of intercurrent illness , and 28 patients could be evaluated . Fewer methotrexate-treated patients ( 6/13 or 46 % ) had flares of Crohn 's disease as compared to placebo-treated patients ( 12/15 or 80 % ) , but this did not achieve statistical significance ( p<0.1 ) . There was a non-significant trend toward an increased number of significant side effects in the methotrexate-treated patients ( 3/13 or 23 % ) as compared to the placebo-treated patients ( 0/15 or 0 % ) ( p<0.2 ) . Laboratory indices of inflammation did not differ between the two groups . CONCLUSIONS The  methotrexate-treated  group showed a trend toward fewer Crohn 's disease flares , balanced by an increased number of significant side effects BACKGROUND & AIMS No therapy has been shown to reliably prevent the evolution of postoperative recurrence of Crohn 's disease . The aim of the current trial was to compare 6-mercaptopurine ( 6-MP ) and mesalamine with placebo for the prevention of clinical , endoscopic , and radiographic recurrence of Crohn 's disease after resection and ileocolic anastomosis . METHODS Five centers r and omized 131 patients to receive 6-MP ( 50 mg ) , mesalamine  ( 3 g ) , or placebo daily in a double-blind , double-dummy trial . Patients had clinical assessment s at 7 weeks and then every 3 months ; colonoscopy at 6 , 12 , and 24 months ; and small bowel series at 12 and 24 months . End points were clinical , endoscopic , and radiographic recurrence rates at 24 months . RESULTS Clinical recurrence rates ( intent to treat ) by life-table analysis at 24 months were 50 % ( 95 % confidence interval [ CI ] , 34%-68 % ) , 58 % ( 95 % CI , 41%-75 % ) , and 77 % ( 95 % CI , 61%-91 % ) in patients receiving 6-MP , mesalamine , and placebo , respectively . Endoscopic recurrence rates were 43 % ( 95 % CI , 28%-63 % ) , 63 % ( 95 % CI , 47%-79 % ) , and 64 % ( 95 % CI , 46%-81 % ) , and radiographic recurrence rates were 33 % ( 95 % CI , 19%-54 % ) , 46 % ( 95 % CI , 29%-66 % ) , and 49 % ( 95 % CI , 30%-72 % ) , respectively . 6-MP was more effective than placebo ( P < 0.05 ) at preventing clinical and endoscopic recurrence over 2 years . Patient withdrawals result ed in 69 % of the study population evaluable for the clinical recurrence end point . CONCLUSIONS 6-MP , 50 mg daily , was more effective than placebo at preventing postoperative recurrence of Crohn 's disease and should be considered as a maintenance therapy after ileocolic resection Introduction : Azathioprine is effective for maintenance of remission in Crohn 's disease , however , duration of efficacy and the dose response relationship has not been fully evaluated Guidelines for clinical practice are intended to suggest preferable approaches to particular medical problems as established by interpretation and collation of scientifically valid research , derived from extensive review of published literature . When data that will withst and objective scrutiny are not available , a recommendation may be made based on a consensus of experts . Guidelines are intended to apply to the clinical situation for all physicians without regard to specialty . Guidelines are intended to be flexible , not necessarily indicating the only acceptable approach , and should be distinguished from st and ards of care that are inflexible and rarely violated . Given the wide range of choices in any health-care problem , the physician should select the course best suited to the individual patient and the clinical situation presented . These guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee . Expert opinion is solicited from the outset for the document . The quality of evidence upon which a specific recommendation is based is as follows : Grade A : Homogeneous evidence from multiple well- design ed r and omized ( therapeutic ) or cohort ( descriptive ) controlled trials , each involving a number of participants to be of sufficient statistical power . Grade B : Evidence from at least one large well- design ed clinical trial with or without r and omization , from cohort or case – control analytic studies , or well- design ed meta- analysis . Grade C : Evidence based on clinical experience , descriptive studies , or reports of expert committees . The Committee review s guidelines in depth , with participation from experienced clinicians and others in related fields . The final recommendations are based on the data available at the time of the production of the document and may be up date d with pertinent scientific developments at a later time BACKGROUND There has been no new effective drug therapy for patients with severe ulcerative colitis since corticosteroids were introduced almost 40 years ago . In an uncontrolled study , 80 percent of 32 patients with active ulcerative colitis refractory to corticosteroid therapy had a response to cyclosporine therapy . METHODS We conducted a r and omized , double-blind , controlled trial in which cyclosporine ( 4 mg per kilogram of body weight per day ) or placebo was administered by continuous intravenous infusion to 20 patients with severe ulcerative colitis whose condition had not improved after at least 7 days of intravenous corticosteroid therapy .  A response to therapy was defined as an improvement in a numerical symptom score ( 0 indicated no symptoms , and 21 severe symptoms ) leading to discharge from the hospital and treatment with oral medications . Failure to respond to therapy result ed in colectomy , but some patients in the placebo group who had no response and no urgent need for surgery were subsequently treated with cyclosporine . RESULTS Nine of 11 patients ( 82 percent ) treated with cyclosporine had a response within a mean of seven days , as compared with 0 of 9 patients who received placebo ( P < 0.001 ) . The mean clinical -activity score fell from 13 to 6 in the cyclosporine group , as compared with a decrease from 14 to 13 in the placebo group . All five patients in the placebo group who later received cyclosporine therapy had a response . CONCLUSIONS Intravenous cyclosporine therapy is rapidly effective for patients with severe corticosteroid-resistant ulcerative colitis Guidelines for clinical practice are aim ed to indicate preferred approaches to medical problems as established by scientifically valid research . Double-blind placebo controlled studies are preferable , but compassionate-use reports and expert review articles are used in a thorough review of the literature conducted through Medline with the National Library of Medicine . When only data that will not withst and objective scrutiny are available , a recommendation is identified as a consensus of experts . Guidelines are applicable to all physicians who address the subject regardless of specialty training or interests and are aim ed to indicate the preferable but not necessarily the only acceptable approach to a specific problem . Guidelines are intended 
    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: We r and omly assigned 71 patients with active chronic Crohn 's disease who were resistant to or intolerant of corticosteroids to treatment with oral cyclosporine ( 5 to 7.5 mg per kilogram of body weight per day ) or placebo for three months . Disease activity was assessed on a clinical grading scale without knowledge of the treatment given . At the end of the treatment period , 22 of the 37 cyclosporine-treated patients ( 59 percent ) had improvement , as compared with 11 of the 34 placebo-treated patients ( 32 percent ) ( P = 0.032 ) . During cyclosporine treatment , there was significant improvement in plasma orosomucoid levels ( P = 0.0025 ) and the Crohn 's Disease Activity Index ( P = 0.00012 ) . The effect of treatment became evident after two weeks . In the subsequent three months , during which the patients were gradually withdrawn from treatment , the improvement continued in 14 of the 37 patients ( 38 percent ) in the cyclosporine group and in 5 of the 34 ( 15 percent ) in the placebo group ( P = 0.034 ) . No serious adverse events were observed . We conclude that cyclosporine has a beneficial therapeutic effect in patients with active chronic Crohn 's disease and resistance to or intolerance of corticosteroids The effect of azathioprine in patients with active Crohn 's disease has been evaluated in a double-blind cross-over trial . Fifteen patients were treated with both azathioprine and placebo : only two improved while on azathioprine , six got worse , and in seven there was no change . The drug seemed to be the cause of deterioration in two of the patients . Although the drug may be of some value in a few patients , it should be used with caution and only when other measures have failed BACKGROUND & AIMS Uncontrolled studies have suggested that methotrexate may be effective in patients with active ulcerative colitis . The aim of this study was to evaluate the effectiveness of oral methotrexate in chronic steroid-dependent ulcerative colitis in a r and omized , double-blind multicenter trial . METHODS Patients with active ulcerative colitis who have received steroids and /or immunosuppressives for at least 4 months during the preceding 12 months with a current Mayo Clinic score of > or = 7 were included in the study .  Methotrexate ( 12.5 mg ) or placebo was added to their treatment once weekly for 9 months . RESULTS Sixty-seven patients were included ( methotrexate , 30 patients , placebo , 37 patients ) . The proportion of patients entering first remission  ( methotrexate , 46.7 % ; placebo , 48.6 % ) , the time to reach first remission  ( methotrexate , 4.1 + /- 1.9 months ; placebo , 3.4 + /- 1.7 months ) , as well as the proportions of patients having a relapse after first remission  ( methotrexate , 64.3 % ; placebo , 44.4 % ) were not significantly different between the two groups . The mean Mayo Clinic score , the mean monthly steroid dose , and the proportion of abnormal laboratory results during the study were also similar . CONCLUSIONS Methotrexate at a weekly oral dose of 12.5 mg was not found to be better than placebo in the induction or maintenance of remission in patients with chronic active ulcerative colitis AIM : To prospect ively evaluate whether a relationship between thiopurine methyltransferase ( TPMT ) activity and incidence of adverse effects ( especially myelotoxicity ) exists , in a long-term follow-up study of a large group of patients with inflammatory bowel disease treated with azathioprine .  METHODS : TPMT activity in red blood cells ( RBC ) was measured by a radiochemical method in 394 consecutive patients with Crohn 's disease ( 238 ) or ulcerative colitis ( 156 ) starting treatment with azathioprine .  The relationship among several variables and TPMT values was assessed , and the correlation between such levels and the incidence of adverse effects was evaluated . RESULTS : Mean TPMT value was 18.6 ± 4 U/mL RBCs ( range 9.4–33.7 ) . No patient had low levels ( < 5 ) , 7.1 % had intermediate levels ( 5–13.7 ) , and 92.9 % had high levels ( > 13.8 ) . Differences ( P < 0.001 ) were demonstrated in TPMT activity depending on the type of inflammatory bowel disease , but not on the remaining variables ( including treatment with 5-aminosalycilates ) . Adverse effects were reported in 74 patients ( 18.8 % ) , the most frequent being gastrointestinal intolerance ( 9.1 % ) and myelotoxicity ( 4.3 % ) . No patient having adverse effects had low TPMT levels . However , mean TPMT activity was lower in those with adverse effects ( 16.6 ± 3 vs 19.1 ± 4 U/mL , P < 0.001 ) . Moreover , the probability of suffering myelotoxicity in the high TPMT group was only 3.5 % , compared with 14.3 % in the TPMT intermediate group ( 95 % CI = 1.37–14.9 ; OR = 4.5 ) . CONCLUSIONS : The strategy of determining TPMT activity in all patients prior to initiating treatment with azathioprine could help to minimize the risk of myelotoxicity , as patients with intermediate TPMT activity had fourfold more risk than high TPMT activity patients BACKGROUND / AIMS Immunosuppression with methotrexate may be useful in the treatment of Crohn 's disease . We tested the efficacy of methotrexate in refractory Crohn 's disease in a r and omized , controlled trial . METHODOLOGY R and omized , double-blind placebo-controlled trial of methotrexate in 33 patients with steroid-dependent Crohn 's disease , 33 % of whom had previously failed therapy with 6-mercaptopurine .  Patients were given placebo or oral methotrexate 15 mg/week , or adjusted up to 22.5 mg/week , for up to 1 year or until treatment failure . Outcome was assessed by reduction in prednisone dosage , Crohn 's Disease Activity Index , hospital admission , and laboratory parameters . RESULTS Four patients were dropped from the study for non-compliance and one because of intercurrent illness , and 28 patients could be evaluated . Fewer methotrexate-treated patients ( 6/13 or 46 % ) had flares of Crohn 's disease as compared to placebo-treated patients ( 12/15 or 80 % ) , but this did not achieve statistical significance ( p<0.1 ) . There was a non-significant trend toward an increased number of significant side effects in the methotrexate-treated patients ( 3/13 or 23 % ) as compared to the placebo-treated patients ( 0/15 or 0 % ) ( p<0.2 ) . Laboratory indices of inflammation did not differ between the two groups . CONCLUSIONS The  methotrexate-treated  group showed a trend toward fewer Crohn 's disease flares , balanced by an increased number of significant side effects BACKGROUND & AIMS No therapy has been shown to reliably prevent the evolution of postoperative recurrence of Crohn 's disease . The aim of the current trial was to compare 6-mercaptopurine ( 6-MP ) and mesalamine with placebo for the prevention of clinical , endoscopic , and radiographic recurrence of Crohn 's disease after resection and ileocolic anastomosis . METHODS Five centers r and omized 131 patients to receive 6-MP ( 50 mg ) , mesalamine  ( 3 g ) , or placebo daily in a double-blind , double-dummy trial . Patients had clinical assessment s at 7 weeks and then every 3 months ; colonoscopy at 6 , 12 , and 24 months ; and small bowel series at 12 and 24 months . End points were clinical , endoscopic , and radiographic recurrence rates at 24 months . RESULTS Clinical recurrence rates ( intent to treat ) by life-table analysis at 24 months were 50 % ( 95 % confidence interval [ CI ] , 34%-68 % ) , 58 % ( 95 % CI , 41%-75 % ) , and 77 % ( 95 % CI , 61%-91 % ) in patients receiving 6-MP , mesalamine , and placebo , respectively . Endoscopic recurrence rates were 43 % ( 95 % CI , 28%-63 % ) , 63 % ( 95 % CI , 47%-79 % ) , and 64 % ( 95 % CI , 46%-81 % ) , and radiographic recurrence rates were 33 % ( 95 % CI , 19%-54 % ) , 46 % ( 95 % CI , 29%-66 % ) , and 49 % ( 95 % CI , 30%-72 % ) , respectively . 6-MP was more effective than placebo ( P < 0.05 ) at preventing clinical and endoscopic recurrence over 2 years . Patient withdrawals result ed in 69 % of the study population evaluable for the clinical recurrence end point . CONCLUSIONS 6-MP , 50 mg daily , was more effective than placebo at preventing postoperative recurrence of Crohn 's disease and should be considered as a maintenance therapy after ileocolic resection Introduction : Azathioprine is effective for maintenance of remission in Crohn 's disease , however , duration of efficacy and the dose response relationship has not been fully evaluated Guidelines for clinical practice are intended to suggest preferable approaches to particular medical problems as established by interpretation and collation of scientifically valid research , derived from extensive review of published literature . When data that will withst and objective scrutiny are not available , a recommendation may be made based on a consensus of experts . Guidelines are intended to apply to the clinical situation for all physicians without regard to specialty . Guidelines are intended to be flexible , not necessarily indicating the only acceptable approach , and should be distinguished from st and ards of care that are inflexible and rarely violated . Given the wide range of choices in any health-care problem , the physician should select the course best suited to the individual patient and the clinical situation presented . These guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee . Expert opinion is solicited from the outset for the document . The quality of evidence upon which a specific recommendation is based is as follows : Grade A : Homogeneous evidence from multiple well- design ed r and omized ( therapeutic ) or cohort ( descriptive ) controlled trials , each involving a number of participants to be of sufficient statistical power . Grade B : Evidence from at least one large well- design ed clinical trial with or without r and omization , from cohort or case – control analytic studies , or well- design ed meta- analysis . Grade C : Evidence based on clinical experience , descriptive studies , or reports of expert committees . The Committee review s guidelines in depth , with participation from experienced clinicians and others in related fields . The final recommendations are based on the data available at the time of the production of the document and may be up date d with pertinent scientific developments at a later time BACKGROUND There has been no new effective drug therapy for patients with severe ulcerative colitis since corticosteroids were introduced almost 40 years ago . In an uncontrolled study , 80 percent of 32 patients with active ulcerative colitis refractory to corticosteroid therapy had a response to cyclosporine therapy . METHODS We conducted a r and omized , double-blind , controlled trial in which cyclosporine ( 4 mg per kilogram of body weight per day ) or placebo was administered by continuous intravenous infusion to 20 patients with severe ulcerative colitis whose condition had not improved after at least 7 days of intravenous corticosteroid therapy .  A response to therapy was defined as an improvement in a numerical symptom score ( 0 indicated no symptoms , and 21 severe symptoms ) leading to discharge from the hospital and treatment with oral medications . Failure to respond to therapy result ed in colectomy , but some patients in the placebo group who had no response and no urgent need for surgery were subsequently treated with cyclosporine . RESULTS Nine of 11 patients ( 82 percent ) treated with cyclosporine had a response within a mean of seven days , as compared with 0 of 9 patients who received placebo ( P < 0.001 ) . The mean clinical -activity score fell from 13 to 6 in the cyclosporine group , as compared with a decrease from 14 to 13 in the placebo group . All five patients in the placebo group who later received cyclosporine therapy had a response . CONCLUSIONS Intravenous cyclosporine therapy is rapidly effective for patients with severe corticosteroid-resistant ulcerative colitis Guidelines for clinical practice are aim ed to indicate preferred approaches to medical problems as established by scientifically valid research . Double-blind placebo controlled studies are preferable , but compassionate-use reports and expert review articles are used in a thorough review of the literature conducted through Medline with the National Library of Medicine . When only data that will not withst and objective scrutiny are available , a recommendation is identified as a consensus of experts . Guidelines are applicable to all physicians who address the subject regardless of specialty training or interests and are aim ed to indicate the preferable but not necessarily the only acceptable approach to a specific problem . Guidelines are intended 
    Output:
    