RESUMEN
Rapid allograft infection complicates liver transplantation (LT) in patients with hepatitis C virus (HCV). Pegylated interferon-α and ribavirin therapy after LT has significant toxicity and limited efficacy. The effect of a human monoclonal antibody targeting the HCV E2 glycoprotein (MBL-HCV1) on viral clearance was examined in a randomized, double-blind, placebo-controlled pilot study in patients infected with HCV genotype 1a undergoing LT. Subjects received 11 infusions of 50 mg/kg MBL-HCV1 (n=6) or placebo (n=5) intravenously with three infusions on day of transplant, a single infusion on days 1 through 7 and one infusion on day 14 after LT. MBL-HCV1 was well-tolerated and reduced viral load for a period ranging from 7 to 28 days. Median change in viral load (log10 IU/mL) from baseline was significantly greater (p=0.02) for the antibody-treated group (range -3.07 to -3.34) compared to placebo group (range -0.331 to -1.01) on days 3 through 6 posttransplant. MBL-HCV1 treatment significantly delayed median time to viral rebound compared to placebo treatment (18.7 days vs. 2.4 days, p<0.001). As with other HCV monotherapies, antibody-treated subjects had resistance-associated variants at the time of viral rebound. A combination study of MBL-HCV1 with a direct-acting antiviral is underway.
Asunto(s)
Anticuerpos Monoclonales/farmacología , Hepacivirus/fisiología , Hepatitis C/tratamiento farmacológico , Trasplante de Hígado , Anciano , Biopsia , Método Doble Ciego , Femenino , Genotipo , Hepatitis C/virología , Humanos , Hígado/patología , Masculino , Persona de Mediana Edad , Proyectos Piloto , ARN Viral/análisis , Factores de Tiempo , Proteínas del Envoltorio Viral/inmunologíaRESUMEN
This study investigated the effect of regular feedback of listener-judged speech naturalness ratings on the speech of stutterers. Six adult stutterers each participated in a time-series ABA experiment. During the treatment phase the stutterer was instructed to improve a clinician's rating, on a 9-point scale, of the naturalness of each 30-s interval of the stutterer's spontaneous speech. The results indicate that the naturalness ratings and stuttering for 5 of the subjects made favorable changes during the treatment phase. Analyses of the findings show that only some of the naturalness judgments were influenced by stuttering frequency and speech rate. A perceptual analysis of the speech of 2 subjects suggested that the speech naturalness ratings were also probably influenced by other less obvious variables.