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- Ljung, Tryggve, et al.
(författare)
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Granulocyte, monocyte/macrophage apheresis for inflammatory bowel disease : the first 100 patients treated in Scandinavia
- 2007
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Ingår i: Scandinavian Journal of Gastroenterology. - Oslo : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 42:2, s. 221-227
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Selective leukocyte apheresis is a new type of non-pharmacological treatment for patients with active ulcerative colitis and Crohn's disease. Preliminary data have indicated that this type of therapy is safe and efficacious, and large sham-controlled studies are currently in progress. In Scandinavia, a substantial number of patients with chronic inflammatory bowel disease have already received leukocyte apheresis on a compassionate use basis and the aim of this study was to report the clinical outcome and adverse events in the first patients treated. MATERIAL AND METHODS: Clinical details of the first consecutive 100 patients with inflammatory bowel disease treated with granulocyte, monocyte/macrophage (Adacolumn) apheresis in Scandinavia were prospectively registered. Median length of follow-up was 17 months, (range 5-30). RESULTS: The study population comprised 52 patients with ulcerative colitis, 44 patients with Crohn's disease and 4 patients with indeterminate colitis. In 97 patients the indication for Adacolumn treatment was steroid-refractory or steroid-dependent disease. Clinical remission was attained in 48% of the patients with ulcerative colitis, and an additional 27% had a clinical response to the apheresis treatment. The corresponding figures for patients with Crohn's disease were 41% and 23%, respectively. Complete steroid withdrawal was achieved in 27 out of the 50 patients taking corticosteroids at baseline. Adverse events were reported in 15 patients and headache was most frequently reported (n=7). CONCLUSIONS: Granulocyte, monocyte/macrophage apheresis treatment seems to be a valuable adjuvant therapy in selected patients with refractory inflammatory bowel disease. The risk for toxicity or severe adverse events appears to be low.
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- von Delwig, Alexei, et al.
(författare)
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Inhibition of macropinocytosis blocks antigen presentation of type II collagen in vitro and in vivo in HLA-DR1 transgenic mice
- 2006
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Professional antigen-presenting cells, such as dendritic cells, macrophages and B cells have been implicated in the pathogenesis of rheumatoid arthritis, constituting a possible target for antigen-specific immunotherapy. We addressed the possibility of blocking antigen presentation of the type II collagen (CII)-derived immunodominant arthritogenic epitope CII259-273 to specific CD4 T cells by inhibition of antigen uptake in HLA-DR1-transgenic mice in vitro and in vivo. Electron microscopy, confocal microscopy, subcellular fractionation and antigen presentation assays were used to establish the mechanisms of uptake, intracellular localization and antigen presentation of CII by dendritic cells and macrophages. We show that CII accumulated in membrane fractions of intermediate density corresponding to late endosomes. Treatment of dendritic cells and macrophages with cytochalasin D or amiloride prevented the intracellular appearance of CII and blocked antigen presentation of CII259-273 to HLA-DR1-restricted T cell hybridomas. The data suggest that CII was taken up by dendritic cells and macrophages predominantly via macropinocytosis. Administration of amiloride in vivo prevented activation of CII-specific polyclonal T cells in the draining popliteal lymph nodes. This study suggests that selective targeting of CII internalization in professional antigen-presenting cells prevents activation of autoimmune T cells, constituting a novel therapeutic strategy for the immunotherapy of rheumatoid arthritis.
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- Wiberg-Itzel, E, et al.
(författare)
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Determination of pH or lactate in fetal scalp blood in management of intrapartum fetal distress: randomised controlled multicentre trial
- 2008
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Ingår i: BMJ (International Edition). - : BMJ. - 0959-8146 .- 0959-8138 .- 1756-1833. ; 63:11, s. 687-689
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Tidskriftsartikel (refereegranskat)abstract
- Objective To examine the effectiveness of pH analysis of fetal scalp blood compared with lactate analysis in identifying hypoxia in labour to prevent acidaemia at birth. Design Randomised controlled multicentre trial. Setting Labour wards. Participants Women with a singleton pregnancy, cephalic presentation, gestational age >= 34 weeks, and clinical indication for fetal scalp blood sampling. Interventions Standard pH analysis (n=1496) or lactate analysis (n=1496) with an electrochemical microvolume (5 mu l) test strip device. The cut-off levels for intervention were pH < 7.21 and lactate > 4.8 mmol/l, respectively. Main outcome measure Metabolic acidaemia (pH < 7.05 and base deficit > 12 mmol/l) or pH < 7.00 in cord artery blood. Results Metabolic acidaemia occurred in 3.2% in the lactate group and in 3.6% in the pH group (relative risk 0.91, 95% confidence interval 0.61 to 1.36). pH <7.00 occurred in 1.5% in the lactate group and in 1.8% in the pH group (0.84, 0.47 to 1.50). There was no significant difference in Apgar scores < 7 at 5 minutes (1.15, 0.76 to 1.75) or operative deliveries for fetal distress (1.02, 0.93 to 1.11). Conclusion There were no significant differences in rate of acidaemia at birth after use of lactate analysis or pH analysis of fetal scalp blood samples to determine hypoxia during labour.
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