Heterogeneity of HVR-1 quasispecies is predictive of early but not sustained virological response in genotype 1b-infected patients undergoing combined treatment with PEG- or STD-IFN plus RBV.

ISDR mutation pattern and HVR-1 quasispecies were analyzed in HCV genotype 1b-infected patients treated with either PEG- or STD-IFN plus ribavirin, in order to find virological correlates of therapy outcome. ISDR region analysis, performed at baseline (T0) and at 4 weeks of therapy (T1), indicated that ISDR mutation pattern was not predictive of response to treatment. Moreover, no selection of putative resistant strains in the first month of therapy was observed. Viral load was not correlated with any parameter of HVR-1 heterogeneity. Among the HVR-1 heterogeneity parameters considered, complexity was inversely correlated to viral load decline at T1. In univariate analysis, complexity, proportion of non synonymous substitutions (NS) and NS/S ratio were lower in patients showing virological response at 6 months of treatment. Complexity was the only parameter independently associated with both decline of viral load at T1 and virological response after 6 months, even after adjustment for confounding variables. At the end of treatment or later, these correlations were lost. Evolution pattern of the HVR-1 quasispecies indicated a strong selective pressure in sustained responders, with complete substitution of pre-existing quasispecies, while minor changes occured in non responders. In relapsers both patterns were present at a similar rate. In conclusion, this study shows that HVR-1 heterogeneity may be involved in the early response to combined IFN-RBV therapy. The loss of correlation between viral heterogeneity and therapy outcome at 6 months of therapy, or later, suggests that other factors may play a role in maintaining sustained response to treatment.

Long-term maintenance of sustained virological response in liver transplant recipients treated for recurrent hepatitis C.

BACKGROUND: The recurrence of hepatitis C viral infection is common after liver transplant, and achieving a sustained virological response to antiviral treatment is desirable for reducing the risk of graft loss and improving patients' survival. AIM: To investigate the long-term maintenance of sustained virological response in liver transplant recipients with hepatitis C recurrence. METHODS: 436 Liver transplant recipients (74.1% genotype 1) who underwent combined antiviral therapy for hepatitis C recurrence were retrospectively evaluated. RESULTS: The overall sustained virological response rate was 40% (173/436 patients), and the mean follow-up after liver transplantation was 11±3.5 years (range, 5-24). Patients with a sustained virological response demonstrated a 5-year survival rate of 97% and a 10-year survival rate of 93%; all but 6 (3%) patients remained hepatitis C virus RNA-negative during follow-up. Genotype non-1 (p=0.007), treatment duration >80% of the scheduled period (p=0.027), and early virological response (p=0.002), were associated with the maintenance of sustained virological response as indicated by univariate analysis. Early virological response was the only independent predictor of sustained virological response maintenance (p=0.008). CONCLUSIONS: Sustained virological response achieved after combined antiviral treatment is maintained in liver transplant patients with recurrent hepatitis C and is associated with an excellent 5-year survival.

Visual factors affecting the rod-and-frame illusion: role of gap size and frame components.

In two studies the effect of the distance between the tip of the rod and the frame sides (gap) in the rod-and-frame (RF) illusion was examined and the effect of a full-square condition was compared with that of two different frame amputations. In both studies, there were more rod-setting errors in the direction of the tilt of the inducing figure with a small gap than with a large one. These findings are consistent with the idea that in the case of small gap size local interactions contribute to determining the RF illusion. The actual length of the rod was varied in order to keep the gap constant across different frame tilts; therefore these findings cannot be due to the co-variation between gap size and frame tilt which is typical of standard apparatuses. The effect of frame amputations was compared to the full-square condition. According to Wenderoth and Beh, amputations that maintain the two orthogonal contours of the square produce the typical angular function of the RF illusion. This prediction was confirmed in both studies. However, results indicate that the full square has a stronger illusory effect in the case of a small degree of tilt of the inducing stimulus, irrespective of gap size. It is suggested that this 'square superiority' effect is related to global, not local, mechanisms. To pursue Wenderoth and Beh's observations, amputations close to the vertical meridian were used in one experiment and those close to the horizontal meridian in the second experiment. Contrary to predictions, these conditions produced overlapping results.

Modulation of the rod-and-frame illusion by additional external stimuli.

The presence of an additional external upright frame was studied in three experiments to separate the role of visuovestibular, global, and local mechanisms in the rod-and-frame illusion (RFI). In the first experiment, carried out in a dark room, the external frame surrounded a large tilted frame. Rod-setting errors to the vertical were abolished with the additional-frame condition (at 22 degrees inner-frame tilt) confirming earlier findings. However, small, residual direct (at 11 degrees inner-frame tilt) and indirect effects (at 33 degrees inner-frame tilt) were still present, indicating the persistence of global visual processing. In the second experiment, the RFI in the dark was compared with the RFI with the lights on. Turning the light on abolished the effect at 22 degrees and 33 degrees frame tilt; however, a small direct effect was maintained at 11 degrees frame tilt. These two studies indicate that the addition of veridical vertical information abolishes the effect owing to visuovestibular mechanisms. In the third experiment, a small rod and frame was used with the lights on (a condition abolishing visual-vestibular interaction). In the case of a small gap between the rod and the inducing frame (a condition which maximises local processing), the effect of the outer upright frame was negligible; this indicates that the additional frame had no effect on local processing. In the case of a large gap (a condition which minimises local processing), the external square reduced the illusion, indicating its modulating effect on visual global processing. Overall, an upright external frame exerts a differential influence depending on which mechanisms contribute most to the RFI in a given experimental condition.

Post-stroke depression, antidepressant treatment and rehabilitation results. A case-control study.

The aim of this study was to assess the specific influence of poststroke depression (PSD) on both basal functional status and rehabilitation results. We performed a case-control study in 290 stroke inpatients, matched for age (+/-1 year) and onset admission interval (+/-3 days) and divided in two groups according to the presence (PSD+) or absence (PSD-) of PSD. All PSD+ patients were treated with antidepressants (AD), mainly with fluoxetine. PSD+ patients, despite similar severity of stroke, showed greater disability in coping with activities of daily living (ADL) on admission and greater disability both in ADL and mobility at discharge than PSD- patients. Although both groups exhibited similar average functional improvement during rehabilitation, PSD- patients were nearly twice as likely to show excellent recovery both on ADL and mobility as PSD+ patients (OR = 1.95, 95% CI = 1.01-3.75 and OR = 2.23, 95% CI = 1.14-4.35, respectively). All AD drugs improved depressive symptoms. Few relevant side effects were observed: fluoxetine was discontinued in 2 patients because of insomnia and in 2 patients because of nausea; paroxetine was stopped in 1 patient because of nausea and dry mouth. Our results confirm the unfavorable influence of PSD on functional outcome, despite pharmacological treatment.