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- Palhagen, S., et al.
(författare)
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Selegiline slows the progression of the symptoms of Parkinson disease
- 2006
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 66:8, s. 1200-1206
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study the long-term effects of selegiline in monotherapy and in combination with levodopa in the early phase of Parkinson disease (PD). Methods: One hundred fifty-seven de novo PD patients were randomized in a double-blind, placebo-controlled study of 7 years' duration. In the monotherapy part, selegiline significantly delayed the initiation of levodopa therapy vs placebo. The authors now report the results from the combination part of the study, in which 140 patients received selegiline or placebo in addition to individually tailored levodopa therapy. Results: Compared with placebo, selegiline slowed the progression of disease disability as measured by the Unified Parkinson Disease Rating Scale (UPDRS) total score (p = 0.003) or by motor (p = 0.002) and Activities of Daily Living (p = 0.0002) subscores. After 5 years in combination therapy, the mean difference in the UPDRS total score was nearly 10 points, with patients receiving placebo having 35% higher scores. Simultaneously, patients receiving placebo needed progressively higher doses of levodopa than patients receiving selegiline, after 5 years, the mean dosage of levodopa was 19% higher with placebo than with selegiline (p = 0.0002). Considering the entire (monotherapy and combination therapy) 7-year study time, there was a trend for selegiline to delay the start of wearing-off fluctuations (hazard ratio 0.55, p = 0.08). In both phases of the study, selegiline was safe and well tolerated. Conclusions: The results of this long-term study confirm earlier findings indicating that selegiline delays the progression of the signs and symptoms of Parkinson disease. Copyright © 2006 by AAN Enterprises, Inc.
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| 2. |
- Sahlin, Sven, et al.
(författare)
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Effect of eyelid botulinum toxin injection on lacrimal drainage
- 2000
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Ingår i: American Journal of Ophthalmology. - 0002-9394 .- 1879-1891. ; 129:4, s. 481-486
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE:To determine the effect of eyelid botulinum toxin injection on the lacrimal drainage and to assess the use of botulinum toxin in dry eye conditions. METHODS: Prospectively, three test groups were examined and one lacrimal system investigated in each person in each group. Botulinum toxin A (3.75 IU) was injected into the medial part of 13 lower eyelids of 13 normal test subjects and the medial part of nine lower eyelids in nine patients with dry eyes. A dose of 2.5 IU was injected into the medial part of 10 lower eyelids and the medial part of 10 upper eyelids of 10 patients with dry eyes. The drop test was used to determine the lacrimal drainage capacity and the blink output, before and after the injection. The subjective effect of the botulinum toxin injection on eye comfort was investigated. RESULTS: Three weeks after lower eyelid botulinum toxin injection, the mean blink output was reduced to 64% (1.19 of 1.87, P < .001) and 70% (0.94 of 1.35, P < .001) of the baseline values in the groups of normal subjects and patients, respectively. After injection in both the upper and lower eyelid, the mean blink output was reduced to 38% (0.54 of 1.41, P < .001) of the baseline value. The patients with dry eyes reported an improved eye comfort in six of nine cases after injection in the lower eyelid and in seven of 10 cases after injection in both the upper and lower eyelid. Adverse effects included one case of increased discomfort for 3 weeks after injection. CONCLUSION: Injection of botulinum toxin into the medial part of the eyelids decreased the lacrimal drainage, suggesting a new way to treat dry eye conditions. Further studies are required to assess the clinical value of this treatment. Copyright (C) 2000 Elsevier Science Inc.
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| 3. |
- Synofzik, M., et al.
(författare)
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Mutant superoxide dismutase-1 indistinguishable from wild-type causes ALS
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP): Policy B - Oxford Open Option B. - 0964-6906 .- 1460-2083. ; 21:16, s. 3568-3574
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Tidskriftsartikel (refereegranskat)abstract
- A reason for screening amyotrophic lateral sclerosis (ALS) patients for mutations in the superoxide dismutase-1 (SOD1) gene is the opportunity to find novel mutations with properties that can give information on pathogenesis. A novel c.352Cgreater thanG (L117V) SOD1 mutation was found in two Syrian ALS families living in Europe. The disease showed unusually low penetrance and slow progression. In erythrocytes, the total SOD1 activity, as well as specific activity of the mutant protein, was equal in carriers of the mutation and family controls lacking SOD1 mutations. The structural stabilities of the L117V mutant and wild-type SOD1 under denaturing conditions were likewise equal, but considerably lower than that of murine SOD1. As analyzed with an ELISA specific for misfolded SOD1 species, no differences were found in the content of misfolded SOD1 protein between extracts of fibroblasts from wild-type controls and from an L117V patient. In contrast, elevated levels of misfolded SOD1 protein were found in fibroblasts from ALS patients carrying seven other mutations in the SOD1 gene. We conclude that mutations in SOD1 that result in a fully stable protein are associated with low disease penetrance for ALS and may be found in cases of apparently sporadic ALS. Wild-type human SOD1 is moderately stable, and was found here to be within the stability range of ALS-causing SOD1 variants, lending support to the hypothesis that wild-type SOD1 could be more generally involved in ALS pathogenesis.
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