Background Crohn’s disease, a form of inflammatory bowel disease, resembles s ome aspects of tuberculosis, leprosy, and paratuberculosis. The role of Mycobact erium avium subspecies paratuberculosis (MAP) in Crohn’s...Background Crohn’s disease, a form of inflammatory bowel disease, resembles s ome aspects of tuberculosis, leprosy, and paratuberculosis. The role of Mycobact erium avium subspecies paratuberculosis (MAP) in Crohn’s disease is controversi al. Methods We tested for MAP by PCR and culture in buffy coat preparations from 28 individuals with Crohn’s disease, nine with ulcerative colitis, and 15 with out inflammatory bowel disease. Findings MAP DNA in uncultured buffy coats was i dentified by PCR in 13 (46%) individuals with Crohn’s disease, four (45%) wit h ulcerative colitis, and three (20%) without inflammatory bowel disease. Viabl e MAP was cultured from the blood of 14 (50%) patients with Crohn’s disease, t wo (22%) with ulcerative colitis, and none of the individuals without inflammat ory bowel disease. Current use of immunosuppressive medication did not correlate with a positive MAP culture. Sequencing of PCR products from MAP cultures confi rmed the presence of the MAP-specific IS900 fragment. Among 11 MAP isolates ass essed, we identified nine strains that were not identical. Interpretation We det ected viable MAP in peripheral blood in a higher proportion of individuals with Crohn’s disease than in controls. These data contribute to the evidence that MA P might be a cause of Crohn’s disease.展开更多
BACKGROUND: Sargramostim, granulocyte-macrophage colony-stimulating factor, a hematopoietic growth factor, stimulates cells of the intestinal innate immune system. Preliminary studies suggest sargramostim may have act...BACKGROUND: Sargramostim, granulocyte-macrophage colony-stimulating factor, a hematopoietic growth factor, stimulates cells of the intestinal innate immune system. Preliminary studies suggest sargramostim may have activity in Crohn’s d isease. To evaluate this novel therapeutic approach, we conducted a randomized, placebocontrolled trial. METHODS: Using a 2∶1 ratio, we randomly assigned 124 patients with moderatetosevere active Crohns disease to receive 6 μg of sargramostim per kilogram per day or placebo subcutaneously for 56 days. Antibio tics and aminosalicylates were allowed; immunosuppressants and glucocorticoids w ere prohibited. The primary end point was a clinical response, defined by a decr ease from baseline of at least 70 points in the Crohns Disease Activity Index (CDAI) at the end of treatment (day 57). Other end points included changes in di sease severity and the healthrelated quality of life and adverse events. RESUL TS: There was no significant difference in the rate of the primary end point of a clinical response defined by a decrease of at least 70 points in the CDAI scor e on day 57 between the sargramostim and placebo groups (54 percent vs. 44 perce nt, P=0.28). However, significantly more patients in the sargramostim group than in the placebo group reached the secondary end points of a clinical response de fined by a decrease from baseline of at least 100 points in the CDAI score on da y 57 (48 percent vs. 26 percent, P=0.01) and of remission, defined by a CDAI sco re of 150 points or less on day 57 (40 percent vs. 19 percent, P=0.01). The rate s of either type o f clinical response and of remission were significantly higher in the sargramost im group than in the placebo group on day 29 of treatment and 30 days after trea tment. The sargramostim group also had significant improvements in the quality o f life. Mildtomoderate injectionsite reactions and bone pain were more com mon in the sargramostim group, and three patients in this group had serious adve rse events possibly or probably related to treatment. CONCLUSIONS: This study wa s negative for the primary end point, but findings for the secondary end points suggest that sargramostim therapy decreased disease severity and improved the qu ality of life in patients with active Crohns disease.展开更多
文摘Background Crohn’s disease, a form of inflammatory bowel disease, resembles s ome aspects of tuberculosis, leprosy, and paratuberculosis. The role of Mycobact erium avium subspecies paratuberculosis (MAP) in Crohn’s disease is controversi al. Methods We tested for MAP by PCR and culture in buffy coat preparations from 28 individuals with Crohn’s disease, nine with ulcerative colitis, and 15 with out inflammatory bowel disease. Findings MAP DNA in uncultured buffy coats was i dentified by PCR in 13 (46%) individuals with Crohn’s disease, four (45%) wit h ulcerative colitis, and three (20%) without inflammatory bowel disease. Viabl e MAP was cultured from the blood of 14 (50%) patients with Crohn’s disease, t wo (22%) with ulcerative colitis, and none of the individuals without inflammat ory bowel disease. Current use of immunosuppressive medication did not correlate with a positive MAP culture. Sequencing of PCR products from MAP cultures confi rmed the presence of the MAP-specific IS900 fragment. Among 11 MAP isolates ass essed, we identified nine strains that were not identical. Interpretation We det ected viable MAP in peripheral blood in a higher proportion of individuals with Crohn’s disease than in controls. These data contribute to the evidence that MA P might be a cause of Crohn’s disease.
文摘BACKGROUND: Sargramostim, granulocyte-macrophage colony-stimulating factor, a hematopoietic growth factor, stimulates cells of the intestinal innate immune system. Preliminary studies suggest sargramostim may have activity in Crohn’s d isease. To evaluate this novel therapeutic approach, we conducted a randomized, placebocontrolled trial. METHODS: Using a 2∶1 ratio, we randomly assigned 124 patients with moderatetosevere active Crohns disease to receive 6 μg of sargramostim per kilogram per day or placebo subcutaneously for 56 days. Antibio tics and aminosalicylates were allowed; immunosuppressants and glucocorticoids w ere prohibited. The primary end point was a clinical response, defined by a decr ease from baseline of at least 70 points in the Crohns Disease Activity Index (CDAI) at the end of treatment (day 57). Other end points included changes in di sease severity and the healthrelated quality of life and adverse events. RESUL TS: There was no significant difference in the rate of the primary end point of a clinical response defined by a decrease of at least 70 points in the CDAI scor e on day 57 between the sargramostim and placebo groups (54 percent vs. 44 perce nt, P=0.28). However, significantly more patients in the sargramostim group than in the placebo group reached the secondary end points of a clinical response de fined by a decrease from baseline of at least 100 points in the CDAI score on da y 57 (48 percent vs. 26 percent, P=0.01) and of remission, defined by a CDAI sco re of 150 points or less on day 57 (40 percent vs. 19 percent, P=0.01). The rate s of either type o f clinical response and of remission were significantly higher in the sargramost im group than in the placebo group on day 29 of treatment and 30 days after trea tment. The sargramostim group also had significant improvements in the quality o f life. Mildtomoderate injectionsite reactions and bone pain were more com mon in the sargramostim group, and three patients in this group had serious adve rse events possibly or probably related to treatment. CONCLUSIONS: This study wa s negative for the primary end point, but findings for the secondary end points suggest that sargramostim therapy decreased disease severity and improved the qu ality of life in patients with active Crohns disease.
