A randomized trial of amantadine and interferon versus interferon alone as initial treatment for chronic hepatitis C.

The aim of this study was to compare, in an open-label study, the efficacy and safety of a combination of interferon (IFN) and amantadine (AMA) with that of IFN alone in previously untreated patients with chronic hepatitis C. A total of 200 patients were randomized to 6 MU of IFN-alpha2a 3 times per week, with 200 mg of AMA daily (n = 99) or to an identical dose of interferon alpha2a (n = 101). Patients were treated for 12 months and observed for 6 months' posttreatment. At the completion of treatment, 28.7% of patients in the monotherapy group and 45.5% in the combination group had a virologic response (P =.014). At 6 months' posttreatment, a sustained virologic response was observed in 16.8% (95% CI: 9-23) of patients with IFN alone versus 29.3% (95% CI: 19-37) of patients who were treated with combination therapy (P =.036). In each of the 2 treatments, genotype was the only predictive parameter for a sustained response. At the logistic regression analysis, therapy and genotype were the only 2 parameters with an independent predictive value. In the combination group, at examination of month 3, hepatitis C virus (HCV)-RNA status had a 97.6% (95% CI: 93-102) positive predictive value and a 50% (95% CI: 37-63) negative predictive value for a sustained virologic clearance. A substantial proportion of naïve patients with chronic hepatitis C have an end-of-treatment and end-of-follow-up virologic and biochemical response to a combination of IFN and AMA. This new treatment appears safe and well tolerated.

Activation of the ornithine decarboxylase-polyamine system and induction of c-fos and p53 expression in relation to excitotoxic neuronal apoptosis in normal and microencephalic rats.

Microencephalic rats obtained by gestational treatment with the DNA alkylating agent methylazoxymethanol, show a remarkable lack of sensitivity to excitotoxic neuropathology caused by systemic injections of the convulsant neurotoxin kainic acid. Taking advantage of this, we have studied in these rats, as well as in normal rats, the relationship between the induction of cellular signals supposedly related to cell death and the neuronal apoptosis consequent to kainic acid administration. While normal rats responded to the excitatory insult with a large and relatively long lasting increase of the activity of the enzyme ornithine decarboxylase and of the concentration of putrescine in some brain regions, these alterations were much smaller in microencephalic rats. Expression of c-fos in brain regions sensitive to kainic acid was quicker but lasted a noticeably shorter time in microencephalic rats as compared to normal animals. A profusion of apoptotic neurons, labeled by an in situ technique, were observed in the olfactory cortex, amygdala and hippocampus of normal rats injected with kainic acid, in particular 48 h and 72 h after drug administration. At corresponding time intervals and with similar topographic localization, neurons expressing p53 protein were observed. By contrast, microencephalic rats displayed only in a few cases and in a small number apoptotic neurons in restricted areas of the ventral hippocampus and entorhinal cortex. Noticeably, in these cases small populations of p53-expressing neurons were also present in the same areas. The present observations clearly show that oncogenes such as c-fos and p53, as well as ornithine decarboxylase which behaves as an immediate-early gene in the brain under certain circumstances, undergo noticeably lower and/or shorter induction in microencephalic rats exposed to excitotoxic stimuli. In these rats, therefore, the cellular signalling pathways studied here and related to excitotoxic sensitivity and commitment to cell death are downregulated as a probable consequence of altered brain wiring.

Apoptosis is induced by excitotoxicity in goldfish retina.

Apoptosis is an important mechanism of cell death that occurs physiologically during development. Recently, it has been shown that the selective pattern of neuronal degeneration in some brain disorders or in excitotoxic animal models, can reveal signs of apoptosis. This work produces evidence that kainic acid, a non-NMDA receptor agonist, induces apoptotic cell death in the goldfish retina. DNA breaks are in situ detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL). This reaction shows a large number of positive cells in the inner nuclear layer 48 hours after intravitreal kainic acid administration. TUNEL staining of apoptotic death was prevented by the non-NMDA glutamate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) but not by the NMDA receptor antagonist MK-801 administration. Ultrastructural changes that occur in kainic acid affected retinal neurons (hypercondensation and clumping of the chromatin and shrinkage of the cytoplasm) are consistent with those described in programmed cell death. Our results indicate that the excitotoxicity of intravitreally injected kainic acid causes the degeneration of those neurons in the goldfish retina, that underwent apoptotic death.

[Mental distress, psychoactive drug use and psychosomatic disorders in two groups of subjects at high risk for the burnout syndrome]. / Disagio mentale, uso di psicofarmaci e malattie psicosomatiche in due gruppi di soggetti a rischio per la sindrome del burnout.

This paper discusses the problem whether burnout is an evidence of a psychological distress subsequently resulting in a clear psychiatric disorder or can be deemed an already well-defined psychiatric syndrome. The aim of this study was: 1) To assess the frequency of psychological distress in two groups of subjects at high risk for burnout; such perceived psychological distress was self-rated as anxiety, depression or impulse dyscontrol by the subjects. 2) To evaluate whether subjects reporting anxiety, depression or impulse dyscontrol showed an higher emotional and mental exhaustion (EME); EME was intended as a marker of burnout. 3) To investigate relationships between self-reported psychoactive drug use or psychosomatic disorders and levels of EME score. 109 air traffic controllers (ATC) and 88 health service professionals (HSP) were given a questionnaire, the Rome burnout inventory (RBI) developed as an easy-to-administer, easy-to-complete self-rating tool to be filled out during breaks in working environments. RBI assessed: a) EME; b) physical exhaustion; c) social support by components of the social network; d) work- and non-work-related stressors; e) self-reported psychosomatic disorders and perceived psychological distress in terms of anxiety, depression, impulse dyscontrol; f) psychoactive drug use. EME was positively related to years in office and was higher in ATC independently from the different seniority between professional groups. By using a factorial ANOVA, subjects with self-reported psychological distress (anxiety, depression, impulse dyscontrol) showed higher levels of the EME score although these levels were not higher in individuals reporting psychoactive drug intake. These findings were the same in both the professional groups. Psychosomatic disorders were significantly more frequent in ATC (chi 2 with Yates' correction); this is likely to be due to an higher overall level of EME score in ATC but ATC and HSP with self-reported psychosomatic disorders did not show higher levels of EME score. There was a different way to refer to perceived psychological distress in the two professional groups. ATC mainly emphasized the role of impulse dyscontrol as a way to express the subjective feelings of an augmenting distress. Otherwise, HSP seemed to stress depression as the proper descriptor of their own psychological distress.

Burnout and health status in Italian air traffic controllers.

This study investigated burnout in air traffic controllers (ATC's). There were 109 Italian ATC's who filled out the Rome Burnout Inventory, a new tool for burnout assessment, during breaks in the working environment. The questionnaire assessed: 1) emotional-mental exhaustion (EME); 2) physical exhaustion (PE); 3) social support by components of the social network; 4) work- and nonwork-related stressors; 5) self-reported psychosomatic and psychiatric disorders. Our data show that the burnout syndrome is closely and positively related to age, years spent in air traffic control, professional dissatisfaction, and to work stressors, but not to nonwork stressors. In our sample, burnout was negatively correlated with social support provided by friends and family. The PE construct seemed to be unreliable in detecting physical burnout in Italian ATC's. Using analysis of variance, subjects with self-reported psychosomatic disorders did not show higher levels of EME scores. Further, EME was positively correlated with self-perceived psychological distress (anxiety, depression and impulse discontrol), but not with physician-rated psychopathology, as revealed by psychoactive drug intake. We suggest that burnout is a construct independent from clinical anxiety or depression.