Thirty years of experience with alumina-on-alumina bearings in total hip arthroplasty

Alumina-on-alumina bearings in total hip arthroplasty have been developed in an attempt to minimise debris and the occurrence of osteolytic lesions. The outstanding tribological properties of this bearing system are explained by low surface roughness, high hardness for major scratch resistance, and high wettability. Since the 1970s, technological improvements in the manufacturing process of alumina components together with a better understanding of Morse taper technology have provided a surgical grade material with high density, high purity and small grains. Published studies on the outcome of total hip arthroplasty performed with this new generation of implants showed high survivorship especially in young and active patients, with survival rates free of revision of 90.8% to 97.4% at ten years. However, concern remains over ceramic liner fracture and squeaking, which has been noted recently with increasing prevalence. This review will discuss the current knowledge on the use of alumina-on-alumina bearings.     

Differential language markers of pathology in Autism,Pervasive Developmental Disorder Not Otherwise Specified and Specific Language Impairment

Language impairment is a common core feature in Pervasive Developmental Disorders (PDD) and Specific Language Impairment (SLI). Many studies have tried to define the specific language profiles of these disorders, some claiming the existence of overlaps, and others conceiving of them as separate categories. Fewer have sought to determine whether and how PDD-NOS language profile, including prosody, differs from those of Autistic Disorder (AD) and SLI. Here, 12 children with AD (mean age 9.75; sd 3.5), 10 with PDD-NOS (mean age 9.83; sd 2.17), and 13 children with SLI (mean age 9.17; sd 3.9) matched for age, sex and academic skills were explored for both receptive and expressive language skills. Prosody was also assessed with an intonation imitation task analyzed through automatic speech processing and compared to 70 typical developing controls matched for age and sex. A similar delay in phonology and vocabulary was observed in the three groups as were significant but variable differences between the groups in syntax, pragmatics and prosody. SLI showed correlations between chronological age and raw scores in all language tasks, while AD and PDD-NOS did not. Furthermore, SLI showed correlation within all raw scores in language tasks. Most of those correlations were also found in PDD-NOS but not in AD. In conclusion, these findings support the hypothesis that language skills in AD and SLI rely on different mechanisms, while PDD-NOS show an intermediate profile sharing some characteristics of both AD and SLI. They also suggest that expressive syntax, pragmatic skills and some intonation features could be considered as language differential markers of pathology, challenging the DSM-V proposal of broad criteria.     

In vitro activities of new 2-substituted quinolines against Leishmania donovani

A series of 9 quinolines and 18 styrylquinolines was evaluated for the drugs' in vitro antileishmanial activities and cytotoxicities. The 7-aroylstyrylquinoline scaffold appeared to be the most promising one, with the most interesting compound, no. 35, exhibiting a 50% inhibitory concentration (IC(50)) of 1.2 μM and a selectivity index value of 121.5. Compound 35 was 10-fold and 8-fold more active than miltefosine and sitamaquine, the reference compounds, with selectivity indexes 607-fold and 60-fold higher, respectively.     

Prior caspofungin exposure in patients with hematological malignancies is a risk factor for subsequent fungemia due to decreased susceptibility in Candida spp.: a case-control study in Paris, France

Infections due to caspofungin-resistant Candida isolates in patients exposed to caspofungin therapy are increasing. We report here a nested case-control study which aimed at identifying factors associated with bloodstream infections caused by Candida spp. having reduced susceptibility to caspofungin (CRSC) in adults suffering from hematological malignancies. In univariate and multivariate analyses, infections with CRSC were associated with caspofungin exposure in the previous 30 days (odds ratio [OR] = 5.25; 95% confidence interval [95% CI], 1.68-16.35) and with an age of ≤ 65 years (OR = 3.27; 95% CI, 1.26-8.50).     

Population pharmacokinetics of nevirapine in HIV-1-infected pregnant women and their neonates

The aim of the present study was to describe the nevirapine (NVP) pharmacokinetics (PK) in pregnant women and their neonates and to evaluate the transplacental drug transfer and administration scheme for the prevention of mother-to-child transmission. Thirty-eight HIV-1-infected pregnant women were administered one tablet of NVP (200 mg) and two tablets of tenofovir-emtricitabine (Truvada) at the initiation of labor. Children were given NVP syrup (2 mg/kg of body weight) as a single dose (sdNVP) on the first day of life. By pair, NVP concentrations were measured in 11 maternal, 1 cord blood, and 2 neonatal plasma samples and analyzed by a population approach. A one-compartment model was used for mothers and neonates; the absorption rate constants for mothers and neonates were 0.95 h(-1) (intersubject variability, 111%) and 0.39 h(-1), respectively; the apparent elimination clearances were 1.42 liter·h(-1) (intersubject variability, 22%) and 0.035 liter·h(-1), respectively; and apparent volumes of distribution were 87.3 liters (intersubject variability, 25%) and 5.65 liters, respectively. An effect compartment was linked to maternal circulation by mother-to-cord and cord-to-mother rate constants of 1.10 h(-1) and 1.43 h(-1), respectively. Placental transfer, expressed as the fetal-to-maternal area under the curve ratio, was 75%. Neonates had a very long half-lives (110 h) compared to adults. In the 38 mothers, the simulated median individual predicted time during which the NVP concentration remained above the half-maximal inhibitory concentration (IC(50)) was 13.2 days (range, 12 to 19.2 days). Thus, the administration of tenofovir-emtricitabine for at least 3 weeks after delivery should be considered to prevent the emergence of resistant viruses. The neonate must receive sdNVP immediately after birth when the infant is born less than 30 min after maternal drug intake to keep NVP concentrations above the IC(50).