Short communication: liver toxicity of lopinavir-containing regimens in HIV-infected patients with or without hepatitis C coinfection

Liver toxicity is a common side effect of antiretroviral therapy, particularly in subjects coinfected with the hepatitis C virus (HCV). The incidence of severe liver toxicity after initiation of treatment with lopinavir (LPV) as well as its possible association with LPV plasma levels were assessed in 120 HIV-infected patients (52% coinfected by HCV). The incidence of severe liver toxicity at 3 months was 1.7% and the cumulative incidence at 12 months was 4%. The development of severe liver toxicity was associated with HCV coinfection but not with LPV plasma levels.     

Refractory bleeding after endoscopic sphincterotomy: a new indication for recombinant factor VII therapy?

The therapeutic approach in post-ERCP bleeding depends on the severity of the episode. In most instances early bleeding is self-limited, but when it is severe enough endoscopic injection of epinephrine (EP) is the usual treatment. Nevertheless, in some cases bleeding relapses, whereas in between 5% and 10% of patients the refractoriness to endoscopic management may even be fatal and other therapeutic alternatives would be needed. Otherwise, in a small subgroup of cases the bleeding becomes massive, the vision is obscured, and the injection may be very difficult in a situation of hemodynamic instability. We here report a case of refractory post-endoscopic sphincterotomy (ES) bleeding in a patient without preexisting coagulopathy, successfully treated with a single injection of rFVII. This novel experience suggests that rFVIIa, besides its actual high costs, might be useful and safe as a second-line, noninvasive, therapeutic tool in selected cases of massive, or refractory, post-ES bleeding.     

Insight in early psychosis: a 1-year follow-up

Insight was investigated in 180 individuals consecutively admitted to a comprehensive early psychosis treatment program. Insight was assessed on admission and after 3, 6 and 12 months. Insight improved significantly over 12 months, and was negatively correlated with both positive and negative symptoms, and positively correlated with depressive symptoms at admission. There were no associations with cognition.     

Kv3 voltage-gated potassium channels regulate neurotransmitter release from mouse motor nerve terminals

Voltage-gated potassium (Kv) channels are critical to regulation of neurotransmitter release throughout the nervous system but the roles and identity of the subtypes involved remain unclear. Here we show that Kv3 channels regulate transmitter release at the mouse neuromuscular junction (NMJ). Light- and electron-microscopic immunohistochemistry revealed Kv3.3 and Kv3.4 subunits within all motor nerve terminals of muscles examined [transversus abdominus, lumbrical and flexor digitorum brevis (FDB)]. To determine the roles of these Kv3 subunits, intracellular recordings were made of end-plate potentials (EPPs) in FDB muscle fibres evoked by electrical stimulation of tibial nerve. Tetraethylammonium (TEA) applied at low concentrations (0.05-0.5 mM), which blocks only a few known potassium channels including Kv3 channels, did not affect muscle fibre resting potential but significantly increased the amplitude of all EPPs tested. Significantly, this effect of TEA was still observed in the presence of the large-conductance calcium-activated potassium channel blockers iberiotoxin (25-150 nM) and Penitrem A (100 nM), suggesting a selective action on Kv3 subunits. Consistent with this, 15-microM 4-aminopyridine, which blocks Kv3 but not large-conductance calcium-activated potassium channels, enhanced evoked EPP amplitude. Unexpectedly, blood-depressing substance-I, a toxin selective for Kv3.4 subunits, had no effect at 0.05-1 microM. The combined presynaptic localization of Kv3 subunits and pharmacological enhancement of EPP amplitude indicate that Kv3 channels regulate neurotransmitter release from presynaptic terminals at the NMJ.     

Dimensional complexity of the neuronal activity in a rat model of depression

The Flinders sensitive line of rats is a widely accepted and validated model of depression. These rats demonstrate abnormalities in limbic dopamine neurotransmission, suggesting disturbed neuronal activity in the ventral tegmental area. Interspike interval time-series were recorded from the ventral tegmental area of control Sprague-Dawley and Flinder sensitive line rats. These data were analyzed using standard measures (mean firing rate, bursting activity and spectral analysis) as well as the pointwise correlation dimension, a nonlinear measurement characterizing the complexity degree of dynamic systems. Pointwise correlation dimension, but not standard analysis revealed a significant difference between the animal lines. Our results suggest that nonlinear analyses can detect dysregulation of the mesolimbic dopaminergic system and shed light on the pathophysiology of depression.     

Cognitive generation of affect in hypomania: an fMRI study

OBJECTIVE: To identify the brain regions associated with the cognitive generation of affect in hypomanic bipolar patients. METHODS: The study examined 10 hypomanic female subjects with bipolar affective disorder, and 10 age- and sex-matched comparison subjects using functional magnetic resonance imaging (fMRI) while viewing alternating blocks of captioned-pictures designed to evoke negative, positive or no affective change. The activation paradigm involved the presentation of the same visual materials over three experiments alternating (a) negative and reference, (b) positive and reference and (c) positive and negative captioned-pictures. RESULTS: The stimuli produced activation in both patients and comparison subjects in brain regions previously implicated in the generation and modulation of affect, in particular the prefrontal cortex. Activation in patients involved additional subcortical regions namely the caudate and thalamus. CONCLUSIONS: This preliminary study suggests that hypomanic patients recruit additional subcortical limbic systems for emotional evaluation when advanced prefrontal cortical processing is no longer sufficient. The differential patterns of activation inform us about bipolar disorder and may have potential diagnostic and therapeutic significance.