Background and aims: Ulcerative colitis disease activity indices offer good statistical power but small changes in these indices may not be clinically important. There are no validated definitions of remission or of s...Background and aims: Ulcerative colitis disease activity indices offer good statistical power but small changes in these indices may not be clinically important. There are no validated definitions of remission or of significant improvement for these indices. The use of clinically important end points would strengthen the validity of study outcomes. Our aims were to identify objective end points in standard disease activity indices for remission and for improvement in ulcerative colitis. Methods: Sixty six consecutive patients with ulcerative colitis provided information about remission status and their disease activity. At a return visit 1-14 months later, these patients provided information about the change in their disease activity, and non-invasive indices were measured. Results: Specific objective end points for determining remission with four standard indices and a quality of life instrument were deter mined (St Mark’s < 3.5, ulcerative colitis disease activity index < 2.5, simple clinical colitis activity index (SCCAI) < 2.5, Seo < 120, and inflammatory bowel disease quality of life index (IBDQ) >205). These cut offs also identified patients who met a regulatory definition of remission. Specific objective end points for clinical improvement in two non-invasive indices and a quality of life instrument were determined with good sensitivity and specificity (SCCAI decrease >1.5, Seo decrease >30, IBDQ increase >20). Conclusions: We found specific cut off values for disease activity indices that identify patients who have significantly improved or achieved remission in an objective, sensitive, and specific manner. These cut offs should help in the interpretation of the outcomes of clinical trials in ulcerative colitis.展开更多
Background: In previous studies, distinct immunological abnormalities have been reported in localized scleroderma (LS). Several pro-inflammatory cytokines have been dem- onstrated at increased levels in sera of patien...Background: In previous studies, distinct immunological abnormalities have been reported in localized scleroderma (LS). Several pro-inflammatory cytokines have been dem- onstrated at increased levels in sera of patients with LS in parallel with disease activity. Human β-defensins (hBDs) are peptides with antimicrobial activity,but have been also shown to be implicated in tissue injury, scarring and wound healing. hBD expression in LS, a condition resembling pathological scarring due to excessive stimulation of matrix synthesis and fibroblast activation, has so far not been investigated. Ultraviolet (UV) A1 phototherapy, the most recent advance in the treatment of LS, targets T-cell dermal inflammatory infiltrates via induction of various cytokines and soluble factors besides well-known effects on collagen metabolism. Objectives: We sought to investigate the effects of UVA1 on the expression and modulation of hBDs and several pro-inflammatory cytokines in LS. Methods: UVA1 phototherapy was performed five times weekly for 8 weeks resulting in a total of 40 treatment sessions (single dose 20 J cm-2, cumulative dose 800 J cm-2). hBD-1, hBD-2 and hBD-3mRNA as well as tumour necrosis factor-α, transforming growth factor-β, interleukin (IL) -2, IL-4, IL-6 and IL-8 mRNA expression were determined by quantitative real-time reverse transcriptionpolymerase chain reaction in lesional and unaffected skin of patients with LS. Results: Skin status markedly improved in all 14 patients, resulting in a significant reduction of the clinical score from baseline to the end of treatment. hBD-1, hBD-2 and hBD-3 mRNA levels were higher in lesional skin compared with unaffected skin and skin from healthy volunteers. Following UVA1 phototherapy, hBD-1 mRNA decreased in lesional, but not in unaffected skin. hBD-3 mRNA levels significantly decreased after UVA1 in lesional skin, whereas an increase of hBD-3 was observed in unaffected skin. IL-6 and IL-8 mRNA levels were significantly elevated in lesional skin and significantly decreased after UVA1 irradiation, whereas mRNA for both cytokines remained unchanged in irradiated unaffected skin. The decrease of hBD-1, hBD-3, IL-6 and IL-8 mRNA paralleled the extent of disease and response to UVA1 phototherapy. Conclusions: hBDs and IL-6 and IL-8, cytokines with pivotal importance in sclerotic skin diseases, are downregulated by UVA1 in the lesional skin of patients with LS. Their pathogenetic relevance with respect to clinical improvement needs further investigation.展开更多
Background: Factors affecting the angiographic recanalization (AR) and clinica l improvement (CI) still remain unclear in pa tients receiving thrombolytic the rapy. Objectives: To elucidate factors related to AR and e...Background: Factors affecting the angiographic recanalization (AR) and clinica l improvement (CI) still remain unclear in pa tients receiving thrombolytic the rapy. Objectives: To elucidate factors related to AR and early CI in patients wi th middle cerebral artery (MCA) or internal carotid artery (ICA) occlusion. Desi gns: Retrospective study. Sotting: Department of Neurology, Asan Medical Center, Seoul, South Korea. Patients: We studied 42 patients who (1) underwent diffu sion weighted magnetic resonance (MR) imaging and MR angiography within 6 hou rs after onset, (2) had MCA territory infarction, (3) had nonvisualization of th e MCA or the ICA on initial MR angiography, (4) were treated with thrombolytics, and (5) underwent followup MR imaging and MR angiography at day 2 or 3. Results :Successful AR and CI were achieved in 31 and 16 patients,respectively. Angiogra phic recanalization was related to CI (P<.01), lower follow up National Institu tes of Health Stroke Scale scores (P<.05), the absence of a dominant ipsilateral posterior cerebral artery (P<.01) on initial MR angiography, and the sparing of the internal capsule on both initial (P<.05) and follow up (P<.01) MR imaging. Clinical improvement was associated with the absence of ICA (vs MCA) flow signa ls (P<.05), the sparing of the internal capsule (P<.01), and marginally, with th e infarct volume change (P=.06). Conclusions: In patients with MCA or ICA occlus ion, CI after thrombolysis is related to the AR and the sparing of the critical motor pathway. The presence of a dominant ipsilateral posterior cerebral artery may predict poor AR after thrombolysis.展开更多
文摘Background and aims: Ulcerative colitis disease activity indices offer good statistical power but small changes in these indices may not be clinically important. There are no validated definitions of remission or of significant improvement for these indices. The use of clinically important end points would strengthen the validity of study outcomes. Our aims were to identify objective end points in standard disease activity indices for remission and for improvement in ulcerative colitis. Methods: Sixty six consecutive patients with ulcerative colitis provided information about remission status and their disease activity. At a return visit 1-14 months later, these patients provided information about the change in their disease activity, and non-invasive indices were measured. Results: Specific objective end points for determining remission with four standard indices and a quality of life instrument were deter mined (St Mark’s < 3.5, ulcerative colitis disease activity index < 2.5, simple clinical colitis activity index (SCCAI) < 2.5, Seo < 120, and inflammatory bowel disease quality of life index (IBDQ) >205). These cut offs also identified patients who met a regulatory definition of remission. Specific objective end points for clinical improvement in two non-invasive indices and a quality of life instrument were determined with good sensitivity and specificity (SCCAI decrease >1.5, Seo decrease >30, IBDQ increase >20). Conclusions: We found specific cut off values for disease activity indices that identify patients who have significantly improved or achieved remission in an objective, sensitive, and specific manner. These cut offs should help in the interpretation of the outcomes of clinical trials in ulcerative colitis.
文摘Background: In previous studies, distinct immunological abnormalities have been reported in localized scleroderma (LS). Several pro-inflammatory cytokines have been dem- onstrated at increased levels in sera of patients with LS in parallel with disease activity. Human β-defensins (hBDs) are peptides with antimicrobial activity,but have been also shown to be implicated in tissue injury, scarring and wound healing. hBD expression in LS, a condition resembling pathological scarring due to excessive stimulation of matrix synthesis and fibroblast activation, has so far not been investigated. Ultraviolet (UV) A1 phototherapy, the most recent advance in the treatment of LS, targets T-cell dermal inflammatory infiltrates via induction of various cytokines and soluble factors besides well-known effects on collagen metabolism. Objectives: We sought to investigate the effects of UVA1 on the expression and modulation of hBDs and several pro-inflammatory cytokines in LS. Methods: UVA1 phototherapy was performed five times weekly for 8 weeks resulting in a total of 40 treatment sessions (single dose 20 J cm-2, cumulative dose 800 J cm-2). hBD-1, hBD-2 and hBD-3mRNA as well as tumour necrosis factor-α, transforming growth factor-β, interleukin (IL) -2, IL-4, IL-6 and IL-8 mRNA expression were determined by quantitative real-time reverse transcriptionpolymerase chain reaction in lesional and unaffected skin of patients with LS. Results: Skin status markedly improved in all 14 patients, resulting in a significant reduction of the clinical score from baseline to the end of treatment. hBD-1, hBD-2 and hBD-3 mRNA levels were higher in lesional skin compared with unaffected skin and skin from healthy volunteers. Following UVA1 phototherapy, hBD-1 mRNA decreased in lesional, but not in unaffected skin. hBD-3 mRNA levels significantly decreased after UVA1 in lesional skin, whereas an increase of hBD-3 was observed in unaffected skin. IL-6 and IL-8 mRNA levels were significantly elevated in lesional skin and significantly decreased after UVA1 irradiation, whereas mRNA for both cytokines remained unchanged in irradiated unaffected skin. The decrease of hBD-1, hBD-3, IL-6 and IL-8 mRNA paralleled the extent of disease and response to UVA1 phototherapy. Conclusions: hBDs and IL-6 and IL-8, cytokines with pivotal importance in sclerotic skin diseases, are downregulated by UVA1 in the lesional skin of patients with LS. Their pathogenetic relevance with respect to clinical improvement needs further investigation.
文摘Background: Factors affecting the angiographic recanalization (AR) and clinica l improvement (CI) still remain unclear in pa tients receiving thrombolytic the rapy. Objectives: To elucidate factors related to AR and early CI in patients wi th middle cerebral artery (MCA) or internal carotid artery (ICA) occlusion. Desi gns: Retrospective study. Sotting: Department of Neurology, Asan Medical Center, Seoul, South Korea. Patients: We studied 42 patients who (1) underwent diffu sion weighted magnetic resonance (MR) imaging and MR angiography within 6 hou rs after onset, (2) had MCA territory infarction, (3) had nonvisualization of th e MCA or the ICA on initial MR angiography, (4) were treated with thrombolytics, and (5) underwent followup MR imaging and MR angiography at day 2 or 3. Results :Successful AR and CI were achieved in 31 and 16 patients,respectively. Angiogra phic recanalization was related to CI (P<.01), lower follow up National Institu tes of Health Stroke Scale scores (P<.05), the absence of a dominant ipsilateral posterior cerebral artery (P<.01) on initial MR angiography, and the sparing of the internal capsule on both initial (P<.05) and follow up (P<.01) MR imaging. Clinical improvement was associated with the absence of ICA (vs MCA) flow signa ls (P<.05), the sparing of the internal capsule (P<.01), and marginally, with th e infarct volume change (P=.06). Conclusions: In patients with MCA or ICA occlus ion, CI after thrombolysis is related to the AR and the sparing of the critical motor pathway. The presence of a dominant ipsilateral posterior cerebral artery may predict poor AR after thrombolysis.
