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Anne‐Grete Mrtson Anette Veringa Edwin R. van den Heuvel Martijn Bakker Daan J. Touw Tjip S. van der Werf Lambert F. R. Span Jan‐Willem C. Alffenaar 《Mycoses》2019,62(8):698-705
Posaconazole is indicated for prophylaxis and treatment of invasive aspergillosis. Therapeutic drug monitoring (TDM) of posaconazole is used to optimise drug exposure. The aim of this study was to analyse and describe the TDM practices and exposure of posaconazole tablets. Patients who received posaconazole for treatment or prophylaxis of fungal infections were included in the study. The following therapeutic window was defined: if concentration was low (<0.7 mg/L for prophylaxis or < 1.5 mg/L for treatment) or high (>3.75 mg/L), the hospital pharmacist provided the physician with dosage advice, which implementation to patient care was analysed. A longitudinal analysis was performed to analyse if different confounding variables had an effect on posaconazole concentrations. Forty‐seven patients were enrolled resulting in 217 posaconazole trough concentrations. A median of 3 (IQR 1‐7) samples was measured per patient. The median concentration was 1.7 mg/L (IQR 0.8‐2.7) for prophylaxis and 1.76 mg/L (IQR 1.3‐2.3) for treatment. Overall, 78 posaconazole concentrations were out of the therapeutic window. For 45 (54%) of these concentrations, a dosage change was recommended. In the longitudinal analysis, the laboratory markers and patient baseline variables did not have an effect on posaconazole concentrations. Adequate posaconazole exposure was shown in 64% (affected 28 patients) of the measured concentrations. TDM practice of posaconazole can be improved by increasing the implementation rate of dose recommendation by a multidisciplinary antifungal stewardship team. 相似文献
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Hiroko Morisaki Gretchen MacCarrick Mark Lindsay David Liang Sarju G. Mehta Jennifer Hague Judith Verhagen Ingrid van de Laar Marja Wessels Yvonne Detisch Mieke van Haelst Annette Baas Klaske Lichtenbelt Kees Braun Denise van der Linde Jolien Roos‐Hesselink George McGillivray Josephina Meester Isabelle Maystadt Paul Coucke Elie El‐Khoury Sandhya Parkash Birgitte Diness Lotte Risom Ingrid Scurr Yvonne Hilhorst‐Hofstee Takayuki Morisaki Julie Richer Julie Désir Marlies Kempers Andrea L. Rideout Gabrielle Horne Chris Bennett Elisa Rahikkala Geert Vandeweyer Maaike Alaerts Aline Verstraeten Hal Dietz Lut Van Laer Bart Loeys 《Human mutation》2018,39(5):621-634
The Loeys–Dietz syndrome (LDS) is a connective tissue disorder affecting the cardiovascular, skeletal, and ocular system. Most typically, LDS patients present with aortic aneurysms and arterial tortuosity, hypertelorism, and bifid/broad uvula or cleft palate. Initially, mutations in transforming growth factor‐β (TGF‐β) receptors (TGFBR1 and TGFBR2) were described to cause LDS, hereby leading to impaired TGF‐β signaling. More recently, TGF‐β ligands, TGFB2 and TGFB3, as well as intracellular downstream effectors of the TGF‐β pathway, SMAD2 and SMAD3, were shown to be involved in LDS. This emphasizes the role of disturbed TGF‐β signaling in LDS pathogenesis. Since most literature so far has focused on TGFBR1/2, we provide a comprehensive review on the known and some novel TGFB2/3 and SMAD2/3 mutations. For TGFB2 and SMAD3, the clinical manifestations, both of the patients previously described in the literature and our newly reported patients, are summarized in detail. This clearly indicates that LDS concerns a disorder with a broad phenotypical spectrum that is still emerging as more patients will be identified. All mutations described here are present in the corresponding Leiden Open Variant Database. 相似文献
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Gottfried Mayer Vitali Vogel J?rg Weyermann Dirk Lochmann Jacomina A van den Broek Christos Tziatzios Winfried Haase Daan Wouters Ulrich S Schubert Andreas Zimmer J?rg Kreuter Dieter Schubert 《Journal of controlled release》2005,106(1-2):181-187
Nanoparticles prepared by self-assembly from oligonucleotides (ONs), protamine free base, and human serum albumin ("ternary proticles") are spheres of diameters around 200 nm. Substitution of the protamine free base by protamine sulfate leads to proticles of only around 40 nm in diameter with otherwise unchanged properties. The availability of drug delivery systems of very similar composition but grossly different size may be advantageous when dealing with cells which show size-dependent particle uptake. These nanoparticles are promising candidates for ON delivery to cells because of the following reasons: (1) They are stable for several hours in solutions of up to physiological ionic strength; (2) they are efficiently taken up by cells; (3) after cellular uptake, they easily release the ONs even when these are present as phosphorothioates. 相似文献
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