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- Clanet, M, et al.
(författare)
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A randomized, double-blind, dose-comparison study of weekly interferon beta-1a in relapsing MS
- 2002
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Ingår i: Neurology. - 1526-632X. ; 59:10, s. 1507-1517
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Tidskriftsartikel (refereegranskat)abstract
- Background: Interferon beta-1a (IFNbeta-1a; Avonex) is effective for the treatment of relapsing MS; however, the optimal dose of IFNbeta-1a is not known. Objective: To determine whether IFNbeta-1a 60 mug IM once weekly is more effective than IFNbeta-1a 30 mug IM once weekly in reducing disability progression in relapsing MS. Methods: In a double-blind, parallel-group, dose-comparison study, 802 patients with relapsing MS from 38 centers in Europe were randomized to IFNbeta-1a 30 mug (n = 402) or 60 mug (n = 400) IM once weekly for greater than or equal to36 months. The primary endpoint was disability progression, defined as time to a sustained increase of greater than or equal to1.0 point on the Expanded Disability Status Scale (EDSS) persisting for 6 months. Additional endpoints included relapses, MRI, safety, immunogenicity, and subgroup analyses of disability progression. Results: Both groups showed equal rates of disability progression (hazard ratio, 0.96; 95% CI, 0.77 to 1.20; p = 0.73). In both groups the proportion of subjects with progression of disability by 36 months estimated from Kaplan-Meier curves was 37%. No dose effects were observed on any of the secondary clinical endpoints. Only one MRI measure at one time point, number of new or enlarging T2 lesions at month 36 compared with month 24, showed a difference favoring the 60-mug dose. Both doses were well tolerated; however, slightly higher incidences of flulike symptoms and muscle weakness were observed in the 60-mug group. The incidences of neutralizing antibodies (titers greater than or equal to20) were 2.3% in the 30-mug group and 5.8% in the 60-mug group. Conclusion: There was no difference between IFNbeta-1a 30 mug and 60 mug IM in clinical or MRI measures.
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| 3. |
- Hohlfeld, Jens M., et al.
(författare)
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Eosinophil cationic protein alters pulmonary surfactant structure and function in asthma
- 2004
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 113:3, s. 496-502
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Impaired surfactant function has been demonstrated in patients with asthma. Inhibitory proteins originating from plasma or inflammatory mediators are good candidates to contribute to this dysfunction. Eosinophils are potent effector cells in asthma, which, on activation, release inflammatory mediators, especially reactive granula proteins such as eosinophil cationic protein (ECP). OBJECTIVE: Because the potential role of ECP in the inhibition of surfactant function is not known, we tested the hypothesis of whether ECP levels in bronchoalveolar lavage fluid (BALF) of patients with asthma after segmental allergen provocation correlate to surfactant dysfunction. Furthermore, we tested the effect of purified ECP on surfactant function and structure in vitro. METHODS: Surfactant isolated from BALF of asthmatic patients was assessed for biophysical function with the Pulsating Bubble Surfactometer and the Capillary Surfactometer and correlated to ECP levels. Purified ECP and plasma proteins at various concentrations were incubated with natural surfactant. Surfactant function was studied with the Capillary Surfactometer, and surfactant structure was determined by electron microscopy. RESULTS: ECP is elevated in BALF from patients with asthma after allergen challenge compared with baseline. ECP levels after allergen challenge correlate well to surfactant dysfunction. In vitro, ECP induces a concentration-dependent inhibition of surfactant function that can be inhibited by antibodies against ECP. ECP is more potent compared with albumin or fibrinogen. Finally, ECP induces severe ultrastructural changes to surfactant vesicles that are more pronounced than changes induced by either fibrinogen or albumin. CONCLUSIONS: ECP contributes to surfactant dysfunction in asthma, which in turn could lead to airway obstruction.
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