1,720,993 research outputs found
Intermittent vs continuous levodopa administration in patients with advanced Parkinson disease: a clinical and pharmacokinetic study.
No full textBACKGROUND: Levodopa-related motor complications can be an important source of disability for patients with advanced Parkinson disease. Current evidence suggests that these motor complications are related to the relatively short half-life of levodopa and its potential to induce pulsatile stimulation of striatal dopamine receptors. Motor complications can be diminished with a continuous infusion of levodopa. OBJECTIVE: To investigate the specific pharmacokinetic changes associated with the benefits of levodopa infusion. DESIGN: We performed an open-label study in 6 patients with Parkinson disease who experienced severe motor complications while receiving standard oral formulations of levodopa/carbidopa. Patients were subsequently treated for 6 months with continuous daytime intraintestinal infusions of levodopa methyl ester. Levodopa pharmacokinetic studies were performed at baseline and 6 months in 3 of these patients. RESULTS: Compared with treatment with intermittent doses of a standard oral formulation of levodopa, continuous infusion provided significant improvement in both "off periods" and dyskinesia. Results of plasma pharmacokinetic studies demonstrated that compared with oral administration, continuous levodopa infusion was associated with a significant increase in the levodopa area under the curve and avoided the low plasma trough levels seen with oral drug administration. CONCLUSIONS: This study confirms that a continuous levodopa infusion is associated with reduced motor complications compared with the standard oral formulation of the drug in patients with advanced PD. Pharmacokinetic studies demonstrate that reduced motor complications are associated with avoiding low plasma levodopa trough levels and are not adversely affected by relatively high plasma levodopa concentrations. We propose that if levodopa/carbidopa could be administered orally in a manner that mirrors the pharmacokinetic pattern of the infusion, it might lead to a similar reduction in motor complications
Pros and cons of a prion-like pathogenesis in Parkinson's disease
Full text linkBackground: Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder which affects widespread areas of the brainstem, basal ganglia and cerebral cortex. A number of proteins are known to accumulate in parkinsonian brains including ubiquitin and alpha-synuclein. Prion diseases are sporadic, genetic or infectious disorders with various clinical and histopathological features caused by prion proteins as infectious proteinaceous particles transmitting a misfolded protein configuration through brain tissue. The most important form is Creutzfeldt-Jakob disease which is associated with a self-propagating pathological precursor form of the prion protein that is physiologically widely distributed in the central nervous system. Discussion: It has recently been found that alpha-synuclein may behave similarly to the prion precursor and propagate between cells. The post-mortem proof of alpha-synuclein containing Lewy bodies in embryonic dopamine cells transplants in PD patient suggests that the misfolded protein might be transmitted from the diseased host to donor neurons reminiscent of prion behavior. The involvement of the basal ganglia and brainstem in the degenerative process are other congruencies between Parkinson's and Creutzfeldt-Jakob disease. However, a number of issues advise caution before categorizing Parkinson's disease as a prion disorder, because clinical appearance, brain imaging, cerebrospinal fluid and neuropathological findings exhibit fundamental differences between both disease entities. Most of all, infectiousness, a crucial hallmark of prion diseases, has never been observed in PD so far. Moreover, the cellular propagation of the prion protein has not been clearly defined and it is, therefore, difficult to assess the molecular similarities between the two disease entities. Summary: At the current state of knowledge, the molecular pathways of transmissible pathogenic proteins are not yet fully understood. Their exact involvement in the pathophysiology of prion disorders and neurodegenerative diseases has to be further investigated in order to elucidate a possible overlap between both disease categories that are currently regarded as distinct entities
Perampanel in Parkinson disease fluctuations: a double-blind randomized trial with placebo and entacapone.
No full textGoing Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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