1,721,007 research outputs found
Levetiracetam therapeutic monitoring in patients with epilepsy: effect of concomitant antiepileptic drugs.
No full textHPLC-UV analysis of thymidine and deoxyuridine in plasma of patients with thymidine phosphorylase deficiency
No full textWe present a simple, fast and validated method for the determination of the two nucleosides thymidine (dThd) and deoxyuridine (dUrd) in plasma of patients with symptoms suggestive of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), using high performance liquid chromatography coupled with ultraviolet spectrophotometric detection (HPLC-UV). Plasma sample (100 mu L) pretreatment was based on simple deproteinization by 1.2 M perchloric acid, using theophylline as internal standard (I.S.). HPLC-UV analysis was carried out on a Synergi 4 mu m Hydro-RP, 150 x 4 mm I.D. column, at room temperature. The mobile phase was a mixture of potassium dihydrogen phosphate buffer (20 mM, pH 4.5) and acetonitrile (95:5, v/v), at an isocratic flow rate of 0.7 mL/min. The UV detector was set at 267 nm. The chromatographic run lasted 19 min. Similar pyrimidine nucleotides and nucleosides do not interfere with the assay. Calibration curves were linear for both dThd and dUrd over a range of 0.5 to 5.0 mu g/mL. The limit of quantitation was 0.5 mu g/mL for both nucleosides and the absolute recovery was >90% for dThd, dUrd and the I.S. Both intra- and inter-assay precision and accuracy were lower than 10% at all tested concentrations. The proposed method was successfully applied to measure plasma concentrations of dThd and dUrd in two MNGIE patients. This assay simplifies both plasma pretreatment and chromatographic conditions of previously reported procedures and describes the first validated method for the determination of the two nucleotides in human plasma
Development and validation of volumetric absorptive microsampling coupled with UHPLC-MS/MS for the analysis of gamma-hydroxybutyric acid in human blood
No full textA volumetric microsampling (VAMS) device (20 μl) was evaluated and validated for the analysis of γ-hydroxybutyric acid (GHB) in venous blood using a simple ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. GHB was extracted from VAMS device by acetonitrile, after a re-hydration step in a temperature-controlled ultrasonic bath at 60°C for 10 min. Chromatographic analysis was carried out on a Kinetex C18 column using 0.1% formic acid in water and acetonitrile as binary gradient mobile phase (from 5 to 95% of acetonitrile from 1 to 2.5 min) at a flow rate of 0.3 ml/min. The VAMS method was fully validated according to current guidelines with satisfactory results in terms of linearity, selectivity, precision, absolute recovery, matrix effect and stability. The linearity was determined from 0.5 to 200 μg/ml and the lower limit of quantitation was 0.5 μg/ml. The novel VAMS-UHPLC-MS/MS method was successfully compared with plasma-based method in a GHB-treated patient as a proof of concept
Mucuna pruriens in Parkinson Disease: A Kinetic-Dynamic Comparison With Levodopa Standard Formulations
No full textObjectives: We compared levodopa (LD) kinetic-dynamic profile of a
dose of LD/aromatic amino acid decarboxylase peripheral inhibitors versus
a nominally equivalent dose of a commercial Mucuna pruriens (Mucuna)
seeds extract in 2 patients with Parkinson disease chronically taking LD
standard combined with self-prescribed Mucuna.
Methods: Patients were challenged with a fasting morning dose of
100 mg LD/25 mg carbidopa (patient 1) or benserazide (patient 2) versus
100 mg LD from Mucuna capsules in 2 different sessions, after a 12-hour
standard LD formulations’ washout. They underwent kinetic-dynamic LD
monitoring based on LD dose intake and simultaneous serial assessments
of plasma drug concentrations and motor test performances. Quantitative
analysis of LD in Mucuna capsules was also performed.
Results: Levodopa bioavailability was markedly lower after Mucuna
administration compared with LD standard formulations: in patient 1, peak
plasma LD concentration (Cmax) decreased from 2.0 to 1.0 mg/L and the
area under the plasma concentration time curve from 137 to 33.6 mg/L
per minute; in patient 2, Cmax was 0.7 mg/L after LD/benserazide and
nearly undetectable afterMucuna. In patient 1, impaired LD bioavailability
from Mucuna resulted in reduced duration and overall extent of drug
response compared with LD/carbidopa. In patient 2, no significant subacute
LD motor response was observed in either condition. Quantitative
analysis of Mucuna formulation confirmed the 100 mg LD content for
the utilized capsules.
Conclusions: Our results show an impaired LD bioavailability from
Mucuna preparation, as expected by the lacking aromatic amino acid decarboxylase
inhibitors coadministration,whichmight explain the suggested lower
dyskinetic potential of Mucuna compared with standard LD formulations
Dyskinesia detection and monitoring by a single sensor in patients with Parkinson's disease
No full textIn current clinical practice, assessment of levodopa-induced dyskinesias (LIDs) in Parkinson's disease (PD) is based on semiquantitative scales or patients' diaries. We aimed to assess the feasibility, clinical validity, and usability of a waist-worn inertial sensor for discriminating between LIDs and physiological sway in both supervised and unsupervised settings
Intrasubject reproducibility of supine norepinephrine plasma concentrations in patients with cardiovascular sympathetic failure
No full textBackground: Plasma levels of the catecholamine norepinephrine (NE) has emerged as a useful tool to help differentiate pre- and post-ganglionic disorders in patients with cardiovascular autonomic failure (AF). However, data on intrasubject reliability in individuals with these conditions are limited. We evaluated the intrasubject reproducibility of supine plasma NE levels drawn across two consecutive time points under controlled conditions during head-up table testing in a large cohort of patients with alpha-synucleinopathies and both pre- and post-ganglionic cardiovascular AF. Methods: Antecubital venous blood drawn via an indwelling cannula with the subject supine was assayed for plasma level of catecholamines. We collected two consecutive samples, the first after 20 min of supine rest (NE1) and the second 5 min later (NE2), from a group of 279 participants including 57 with Parkinson's disease/Lewy body dementia (44 M; 65.5 ± 11.1 y), 131 with multiple system atrophy (81 M; 63.2 ± 8.5 y), 41 with pure autonomic failure (25 M, 65.1 ± 9.3 y), and 50 healthy controls (27 M; 46.7 ± 19.4 y). Results: We found no difference between NE1 and NE2 (p = 0.645), with a mean intrasubject reproducibility (NE maximum − NE minimum) × 100 / NE maximum) of 11.5 % ± 10.64. This finding was confirmed when controlling for diagnosis (p = 0.669), gender (p = 0.493), age (p = 0.865), disease duration (p = 0.596) or considering all factors together (p = 0.527). Conclusions: We found excellent test-retest reliability of consecutive supine NE measurements in patients with alpha-synucleinopathies and cardiovascular AF, independent of age, gender and disease duration. This lends evidence to support the use of a single supine NE measurement in these conditions
Going 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
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