Acute effects of nicotine on attention and response inhibition

Smoking is highly prevalent among patients with Attention Deficit Hyperactivity Disorder (ADHD). Previous studies using the reversed continuous performance task (R-CPT) have suggested that nicotine reduces inattention. Since especially adults with ADHD have been claimed to suffer from a core deficit in inhibitory control, this study aimed at determining whether nicotine improves response inhibition in addition to attention. Sixteen healthy regular smokers participated in a pre/post treatment design in which transdermal patches containing 7 and 21 mg nicotine per day were administered in a counterbalanced, double-blind manner. In a second study, patches containing 0 mg (placebo) and 21 mg per day were administered to a different group of regular smokers. For replication purposes, the R-CPT and the profile of mood states (POMS) were administered. Furthermore, a different version of the continuous performance task (CPT-AX) and the stop-signal task, traditionally used to measure response inhibition, were presented. The high dose of nicotine was found to relieve self-reported Depression in Study 1 and Fatigue in Study 2. Performance data indicated acute effects of nicotine on attention-related, but not on inhibition-related measures. Especially the comparison with placebo revealed decreases in reaction time and variability of responding. The results imply that patients with ADHD smoke to reduce inattention.     

Alterations in nitric oxide production in 8-week-old lambs with increased pulmonary blood flow

Nitric oxide (NO) is an important mediator of pulmonary vascular reactivity, and decreased NO synthase expression has been demonstrated in children with advanced pulmonary hypertension secondary to congenital heart disease and increased pulmonary blood flow. Using aortopulmonary vascular graft placement in the fetal lamb, we have established a unique animal model of pulmonary hypertension with increased pulmonary blood flow. At 4 wk of age, these lambs display an early, selective impairment in agonist-induced NO responses, but an up-regulation of basal NO activity and gene expression. We hypothesized that further exposure to increased flow and/or pressure results in progressive endothelial dysfunction and a subsequent decrease in basal NO production. The objective of this study was to characterize potential later alterations in agonist-induced NO responses and basal NO activity and gene expression induced by 8 wk of increased pulmonary blood flow and pulmonary hypertension. Twenty-two fetal lambs underwent in utero placement of an aortopulmonary vascular graft (shunt), and were studied 8 wk after delivery. Both in vivo and in isolated pulmonary arteries, the pulmonary vasodilating response to endothelium-dependent agents was attenuated in shunted lambs (p < 0.05), whereas the response to endothelium-independent agents was unchanged. The pulmonary vasoconstricting responses to Nomega-nitro-L-arginine, and lung tissue endothelial NO synthase mRNA, endothelial NO synthase protein, NO synthase activity, and NO(X) levels were all unchanged. These data suggest that the increase in basal NO activity demonstrated after 4 wk of increased pulmonary blood flow is lost by 8 wk of age, whereas the attenuation of agonist-induced responses persists. We speculate that the progressive decrease in basal NO activity participates in the development of pulmonary hypertension secondary to increased pulmonary blood flow.     

Haematological parameters of HIV-1-uninfected infants born to HIV-1-infected mothers

Aim: To investigate haematological parameters in infants born to HIV-1-infected mothers and exposed to combination antiretroviral therapy (ART) used to prevent mother-to-child transmission (MTCT). Methods: A 2-y single-centre follow-up study performed in 109 infants born to HIV-1-positive mothers. Exclusion criteria for the infants were HIV-1 infection, perinatal death, or insufficient information. Haematological parameters of the remainder of 92 infants born to HIV-1-infected mothers and exposed to ART in utero and neonatally were compared with 75 matched non-ART-exposed children. Results: Transmission rate of HIV-1 was 1.8% and occurred when the mother was not compliant with the treatment. In the HIV-1/ART-exposed children there was a long-lasting reduction in absolute neutrophil counts (ANC) until at least 8 mo of age. According to PACTG toxicity scores, 16 infants were suffering from grade II or more (moderate-to-severe) toxicity of ART on ANC. In a multivariable analysis of maternal and neonatal risk factors, pregnancy duration was correlated with moderate-to-severe toxicity on ANC. There were no clinical implications detected, e.g. increased infections or antibiotic treatment.

Conclusion: ART is successful in preventing MTCT, but alterations in haematological parameters may persist for a long period. The clinical implications remain uncertain. This suggestion increases the importance to continue prospective follow-up on the haematological parameters in ART/HIV-exposed children.