Disposition of total and unbound prednisolone in renal transplant patients receiving anticonvulsants

AbstractDisposition of total and unbound prednisolone in renal transplant patients receiving anticonvulsants. Kidney transplant patients receiving phenytoin or phenobarbital may have decreased graft survival. These drugs have been shown to enhance the metabolism of glucocorticoids. We determined the disposition of total and unbound prednisolone in six stable kidney transplant patients receiving prednisone for immunosuppression and phenytoin or phenobarbital for a seizure disorder. Six similar patients not on anticonvulsants served as controls. A single intravenous dose of prednisolone was administered, and plasma samples were analyzed for prednisolone using a high-performance liquid chromatographic assay. Equilibrium dialysis was used to determine unbound prednisolone concentrations. Pharmacokinetic analysis showed that the half-life of prednisolone was shorter in the anticonvulsant group compared to the controls, based on both total (2.3 ± 0.4 vs. 3.4 ± 0.2hr (SD), P < 0.01) and unbound (1.7 ± 0.3 vs. 2.4 ± 0.2 hr, P < 0.01) concentrations. Total drug clearance was 10.4 ± 2.8 liters/hr (0.171 ± 0.087 liters/hr · kg) in the anticonvulsant group versus 7.2 ± 1.2 liters/hr (0.100 ± 0.014 liters/hr · kg) in the controls (P < 0.05). Unbound prednisolone clearance was 57.2 ± 12.1 versus 46.4 ± 8.7 liters/hr (P > 0.05) and for weight-corrected estimates 0.886 ± 0.224 liters/hr · kg versus 0.644 ± 0.115 liters/hr · kg (P < 0.05) in the two groups, respectively. Thus, the disposition of prednisolone is altered by anticonvulsants in kidney transplant patients and may require dose alteration.Disparition de la prednisolone totale et libre chez des transplantés rénaux recevant des anticonvulsivants. Les transplantés rénaux recevant de la phénytoïne ou du phénobarbital pourraient avoir une survie du greffon diminuée. Ces médicaments se sont avérés capables de stimuler le métabolisme des glucocorticoïdes. Nous avons déterminé l'élimination de la prednisolone totale et libre chez six transplantés rénaux stables recevant de la prédnisone pour leur immunosuppression et de la phénytoïne ou du phénobarbital pour une épilepsie. Six malades identiques sans anticonvulsivants ont servi de contrôle. Une dose unique intraveineuse de prednisolone a été administrée, et des échantillons plasmatiques ont été analysés pour la prednisolone en utilisant un dosage par chromatographie liquide à haute pression. Une dialyse à l'équilibre a été utilisée pour déterminer les concentrations de prednisolone non liée. L'analyse pharmacocinétique a montré que la demi-vie de la prednisolone était plus courte dans le groupe aux anticonvulsivants par rapport aux contrôles, qu'il s'agisse des concentrations totales (2,3 ± 0,4 contre 3,4 ± 0,2hr (SD), P < 0,01) ou libres (1,7 ± 0,3 contre 2,4 ± 0,2 hr, P < 0,01). La clearance totale du médicament était de 10,4 ± 2,8 litres/hr (0,171 ± 0,087 litres/hr · kg) dans le groupe anticonvulsivant contre 7,2 ± 1,2 litres/hr (0,100 ± 0,014 litres/hr· kg) chez les contrôles (P < 0,05). La clearance de la prednisolone non liée était de 57,2 ±12,1 contre 46,4 ± 8,7 litres/hr (P > 0,05), et après correction pour le poids de 0,886 ± 0,224 litres/hr · kg contre 0,644 ± 0,115 litres/hr · kg (P < 0,05) dans les deux groupes, respectivement. Ainsi, l'élimination de la prednisolone est altérée par les anticonvulsivants chez les transplantés rénaux et peut imposer des modifications de la dose

The socialist blues? Citizenship, class and civil society

This article seeks to explore the relationship between the British labour movement, the Left and the Labour party. It does so through the intellectual prism of debates around citizenship and civil society. In this respect, I seek to recover a critical politics around questions of class from the New Left who were always critical of more mainstream ideas of citizenship. However, I also point to the limitations of those who have argued that meaningful forms of citizenship can no longer be connected to political parties and only occurs outside of state organizations. Political parties continue to need intellectual narratives to legitimate their role in society and to connect with the broader civil order.The Labour Party in this respect has seemingly broken with ‘New Labour’ and is searching for a new narrative. The rise of an intellectual grouping around ‘Blue Labour’ has made considerable headway recently and I seek to take a critical view of some of their ideas and ethical frameworks. Here I argue that changing class formations and a more pluralistic society potentially ask difficult questions of those who seek to revive the labour movement in troubled times

Oxygen-induced giant grain growth in Ag films

Thin film crystallites typically exhibit normal or abnormal growth with maximum grain size limited by energetic and geometric constraints. Although epitaxial methods have been used to produce large single crystal regions, they impose limitations that preclude some compelling applications. The generation of giant grain thin film materials has broad implications for fundamental property analysis and applications. This work details the production of giant grains in Ag films (2.5 μm-thick), ranging in size from 50 μm to 1 mm, on silicon nitride films upon silicon substrates. The presence of oxygen during film deposition plays a critical role in controlling grain size and orientation. Crystallography, Crystallographic defects, Epitaxy, Transition metals, Thin film deposition, Thermal effects, X-ray diffraction, Chemical elements, Mechanical stressUnited States. Office of Naval Research (ONR/NRL Core funding