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Mattsson N.,Sahlgrenska University Hospital | Mattsson N.,University of California at San Francisco | Andreasson U.,Sahlgrenska University Hospital | Persson S.,Sahlgrenska University Hospital | And 30 more authors.
Alzheimer's and Dementia | Year: 2013

Background: The cerebrospinal fluid (CSF) biomarkers amyloid beta 1-42, total tau, and phosphorylated tau are used increasingly for Alzheimer's disease (AD) research and patient management. However, there are large variations in biomarker measurements among and within laboratories. Methods: Data from the first nine rounds of the Alzheimer's Association quality control program was used to define the extent and sources of analytical variability. In each round, three CSF samples prepared at the Clinical Neurochemistry Laboratory (Mölndal, Sweden) were analyzed by single-analyte enzyme-linked immunosorbent assay (ELISA), a multiplexing xMAP assay, or an immunoassay with electrochemoluminescence detection. Results: A total of 84 laboratories participated. Coefficients of variation (CVs) between laboratories were around 20% to 30%; within-run CVs, less than 5% to 10%; and longitudinal within-laboratory CVs, 5% to 19%. Interestingly, longitudinal within-laboratory CV differed between biomarkers at individual laboratories, suggesting that a component of it was assay dependent. Variability between kit lots and between laboratories both had a major influence on amyloid beta 1-42 measurements, but for total tau and phosphorylated tau, between-kit lot effects were much less than between-laboratory effects. Despite the measurement variability, the between-laboratory consistency in classification of samples (using prehoc-derived cutoffs for AD) was high (>90% in 15 of 18 samples for ELISA and in 12 of 18 samples for xMAP). Conclusions: The overall variability remains too high to allow assignment of universal biomarker cutoff values for a specific intended use. Each laboratory must ensure longitudinal stability in its measurements and use internally qualified cutoff levels. Further standardization of laboratory procedures and improvement of kit performance will likely increase the usefulness of CSF AD biomarkers for researchers and clinicians. © 2013 The Alzheimer's Association. All rights reserved.

Mahmoudi A.,University of Paris 13 | Sellier N.,University of Paris 13 | Reboul-Marty J.,Service de sante publique | Chales G.,Rennes University Hospital Center | And 7 more authors.
Clinics and Research in Hepatology and Gastroenterology | Year: 2011

Background/aim: Cirrhosis is considered as a risk factor for osteoporosis whose prevalence is poorly known. The aim was to assess prospectively bone mineral density (BMD) in patients with alcoholic or viral compensated cirrhosis. Methods: From 2006 to 2008, patients with viral or alcoholic compensated cirrhosis had BMD assessment by dual-energy X-ray absorptiometry. The prevalence of osteopenia (-2.5 SD < T-score < -1 SD) and osteoporosis (T-score ≤ -2.5. SD), and the influence of age, gender and aetiology of cirrhosis were assessed using univariate and multiple regression analysis. Results: One hundred and nine patients were studied (72 men, 55.3 ± 11.4 years and 37 women, 65.2 ± 11.0); with HBV (n=35), HCV (n=43), or alcoholic cirrhosis (n=31). At the lumbar spine, 25 patients had osteopenia and 12 had osteoporosis. At the femoral site, 23 had osteopenia and 4 had osteoporosis. Female gender had an independent decreased effect on the total BMD. Conclusions: The prevalence of osteoporosis was up to 11% at the lumbar spine, greater in women independently of age, without significant difference according to the aetiology of cirrhosis. © 2011 Elsevier Masson SAS.

Dufour-Rainfray D.,Laboratoire Of Medecine Nucleaire | Dufour-Rainfray D.,University of Tours | Dufour-Rainfray D.,French Institute of Health and Medical Research | Moal V.,CHRU DAngers | And 16 more authors.
Annales de Biologie Clinique | Year: 2015

Steroid hormone measurement, first developed with radioimmunoassay, is now becoming easier with the use of automated platforms of immunoassay. However, some hormones remain uneasily detectable because of their low blood concentration, their structural homology or the presence of interferences. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) can be considered as an alternative to immunoassays. This approach allows the simultaneous determination of several parameters thanks to its selectivity led by the detector mass spectrometer and the separate dimension of chromatography liquid. In addition, recourse to UHPLC (ultra high performance liquid chromatography) allows improving selectivity and sensitivity while limiting the samples volumes. The "ready-to-use" kits are now available and added to the "homemade" techniques developed by laboratories, thus giving opportunity for measurement of a wide steroid panel with only one sample. Finally, mass spectrometry methods, including a prior extraction step, allow the use of varied biological fluids (blood, urine, saliva. . .). Also, several clinical indications could gain from mass spectrometry, especially when hormone levels are low, when several steroids have to be identified, when the sample volume is low. However, this technology represents an important financial investment and indepth staff training. In addition, some steroids are not easily quantifiable by mass spectrometry. It is likely by immunoassay and mass spectrometry, wellmatched technologies, that we could answer the best to clinical questions about steroids.

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