Laboratory tests in patients treated with isotretinoin: occurrence of liver and muscle abnormalities and failure of AST and ALT to predict liver abnormality.

Current laboratory monitoring may not be optimal. A retrospective chart review was performed on thelaboratory results of 246 patients who were treated with isotretinoin for acne over a 9-year period. Tests obtained were CBC, lipid panel, AST, ALT, CK, GGT,and C-reactive protein. Thirty-five patients had an elevated AST and 35 of these had an elevated CK; 32 had an elevated ALT and 11 of these had an elevated CK. Thirteen patients had an elevated GGT; in 5 this was the only abnormality, whereas 8 had a GGT elevation accompanied by an elevated AST or ALT. Two had an elevated GGT and an elevated CK with normal AST and ALT. Fifty-two patients had a single episode of elevated CK, of which 22 were female. However, 57 had multiple CK elevations and only one was female. Thirty-five patients had CK elevationsnormal; 38 had levels between 2 and 3 times normal, 18 had levels between 3 and 4 times normal, and 18 had levels greater than 4 times normal. We suggest that ALT and AST are not useful for monitoring isotretinoin therapy and that GGT and CK may be of greater value in managing patients

Portraits of people with dementia : three case studies of creating portraits

Peer reviewedPreprin

Pharmacological activation of endogenous protective pathways against oxidative stress under conditions of sepsis

Funding The study was funded entirely by institutional funds.Peer reviewedPostprin

Role of the exchange and correlation potential into calculating the x-ray absorption spectra of half-metallic alloys: the case of Mn and Cu K-edge XANES in Cu2_2MnM (M = Al, Sn, In) Heusler alloys

This work reports a theoretical study of the x-ray absorption near-edge structure spectra at both the Cu and the Mn K-edge in several Cu$_2$MnM (M= Al, Sn and In) Heusler alloys. Our results show that {\it ab-initio} single-channel multiple-scattering calculations are able of reproducing the experimental spectra. Moreover, an extensive discussion is presented concerning the role of the final state potential needed to reproduce the experimental data of these half-metallic alloys. In particular, the effects of the cluster-size and of the exchange and correlation potential needed in reproducing all the experimental XANES features are discussed.Comment: 15 pages, 5 figure

Experimental and finite element analysis of the mouse caudal vertebrae loading model: prediction of cortical and trabecular bone adaptation

In this study, we attempt to predict cortical and trabecular bone adaptation in the mouse caudal vertebrae loading model using knowledge of bone's local mechanical environment at the onset of loading. In a previous study, we demonstrated appreciable 25.9 and 11% increases in both trabecular and cortical bone volume density, respectively, when subjecting the fifth caudal vertebrae (C5) of C57BL/6 (B6) mice to an acute loading regime (amplitude of 8N, 3000 cycles, 10 Hz, 3 times a week for 4 weeks). We have also established a validated finite element (FE) model of the C5 vertebra using micro-computed tomography (micro-CT), which characterizes, in 3D, the micro-mechanical strains present in both cortical and trabecular compartments due to the applied loads. To investigate the relationship between load-induced bone adaptation and mechanical strains in-vivo and in-silico data sets were compared. Using data from the previous cross-sectional study, we divided cortical and trabecular compartments into 15 subregions and determined, for each region, a bone formation parameter ΔBV/BS (a cross-sectional measure of the bone volume added to cortical and trabecular surfaces following the described loading regime). Linear regression was then used to correlate mean regional values of ΔBV/BS with mean values of mechanical strains derived from the FE models which were similarly regionalized. The mechanical parameters investigated were strain energy density (SED), the orthogonal strains (e x , e y , e z ) and the three shear strains (e xy , e yz , e zx ). For cortical regions, regression analysis showed SED to correlate extremely well with ΔBV/BS (R 2 =0.82) and e z (R 2=0.89). Furthermore, SED was found to predict expansion of the cortical shell correlating significantly with the regional percentage increases in cortical tissue volume (R 2 = 0.92), cortical marrow volume (R 2 =0.91) and cortical thickness (R 2 = 0.56). For trabecular regions, FE parameters were found not to correlate with load-induced trabecular bone morphology. These results indicate that load-induced cortical morphology can be predicted from population data, whereas the prediction of trabecular morphology requires subject-specific micro- architectur

Effect of HIV infection and antiretroviral therapy on hepatitis B virus (HBV)-specific T cell responses in patients who have resolved HBV infection

Coinfection with hepatitis B virus (HBV) is a common occurrence in human immunodeficiency virus (HIV)–positive patients and an increasing cause of morbidity and mortality. The CD8+ T cell response is critical for long-term control of HBV in patients resolving acute infection. Here, we examine the effect of HIV on HBV-specific CD8+ T cell responses in patients who have resolved HBV infection. A cross-sectional study showed a reduction in HBV-specific CD8+ T cell responses in HIV-positive, HBV-immune patients, compared with those in HIV-negative, HBV-immune patients. A longitudinal study of a subgroup of patients examined whether this attrition could be reversed by effective antiretroviral therapy. The introduction of highly active antiretroviral therapy (HAART) resulted in reconstitution of some HBV-specific CD4+ and CD8+ T cell responses, in association with restoration of CD4+ T cell counts. These data provide a mechanism to account for the observed impairment of control of HBV infection in the setting of HIV infection and support the ability of HAART to reconstitute functionally active T cell responses

Modeling microevolution in a changing environment: The evolving quasispecies and the Diluted Champion Process

Several pathogens use evolvability as a survival strategy against acquired immunity of the host. Despite their high variability in time, some of them exhibit quite low variability within the population at any given time, a somehow paradoxical behavior often called the evolving quasispecies. In this paper we introduce a simplified model of an evolving viral population in which the effects of the acquired immunity of the host are represented by the decrease of the fitness of the corresponding viral strains, depending on the frequency of the strain in the viral population. The model exhibits evolving quasispecies behavior in a certain range of its parameters, ans suggests how punctuated evolution can be induced by a simple feedback mechanism.Comment: 15 pages, 12 figures. Figures redrawn, some additional clarifications in the text. To appear in Journal of Statistical Mechanics: Theory and Experimen