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Right ventricular (RV) function and autonomic dysfunction are important determinants of morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Although successful in animal studies, effects of beta-blocker therapy on RV function in clinical trials were disappointing. To understand this discrepancy, we studied whether beta-blocker therapy changes RV sympathetic activity. Idiopathic PAH (IPAH) patients received beta-blocker therapy (uptitrated to a maximal tolerated dose) and underwent cardiac magnetic resonance imaging, right heart catheterization, and a [ 11 C]-hydroxyephedrine positron emission tomography ([ 11 C]HED PET) scan at baseline to determine, respectively, RV ejection fraction (RVEF), RV pressures, and sympathetic activity. [ 11 C]HED, a norepinephrine analogue, allows determination of sympathetic innervation of the RV. [ 11 C]HED retention index reflects norepinephrine transporter activity. As a consequence of excessive catecholamine levels in the synaptic cleft, this transporter may be downregulated. Therefore, low [ 11 C]HED retention index indicates high sympathetic activity. 13 IPAH patients underwent [ 11 C]HED PET scans at baseline and after bisoprolol treatment. Although heart rate was reduced, systemic modulation of autonomic activity by bisoprolol did not affect local RV sympathetic nerve activity, RV function, or RV wall tension. In PAH patients, RV [ 11 C]HED retention index was lower compared to LV tracer uptake (p

Background Prevention guidelines for infants at high risk of allergic disease recommend hydrolysed formula if formula is introduced before 6 months, but evidence is mixed. Adding specific oligosaccharides may improve outcomes. Objective To evaluate whether partially hydrolysed whey formula containing oligosaccharides (0.8 g/100 ml) (pHF‐OS) can prevent eczema in high‐risk infants [ISRCTN65195597]. Methods We conducted a parallel‐group, multicentre, randomized double‐blind controlled trial of pHF‐OS vs standard cow's milk formula. Infants with a family history of allergic disease were randomized (stratified by centre/maternal allergy) to active (n = 432) or control (n = 431) formula until 6 months of age if formula was introduced before 18 weeks. Primary outcome was cumulative incidence of eczema by 12 months in infants randomized at 0–4 weeks (375 pHF‐OS, 383 control). Secondary outcomes were cumulative incidence of eczema by 12 or 18 months in all infants randomized, immune markers at 6 months and adverse events. Results Eczema occurred by 12 months in 84/293 (28.7%) infants allocated to pHF‐OS at 0‐4 weeks of age, vs 93/324 (28.7%) control (OR 0.98 95% CI 0.68, 1.40; P = 0.90), and 107/347 (30.8%) pHF‐OS vs 112/370 (30.3%) control in all infants randomized (OR 0.99 95% CI 0.71, 1.37; P = 0.94). pHF‐OS did not change most immune markers including total/specific IgE; however, pHF‐OS reduced cow's milk‐specific IgG1 (P < 0.0001) and increased regulatory T‐cell and plasmacytoid dendritic cell percentages. There was no group difference in adverse events. Conclusion pHF‐OS does not prevent eczema in the first year in high‐risk infants. The immunological changes found require confirmation in a separate cohort.

Atopic dermatitis (AD) is a complex disorder characterized by flares of red and itchy skin. Infants with AD often also suffer from food allergy. Both ingestion of and skin contact with the antigen can exacerbate the AD. The affected skin is characterized by oedema formation and shows typical Th2 responses by increased levels of IL-4 and IL-13, but not IFN-γ. Furthermore, there is an influx of eosinophils and CD4+ cells. The CD4+ cells are previously described to originate from the gut mucosa where they developed upon oral sensitization to the food allergen. From both specific oligosaccharides and TLR ligands, it is clinically demonstrated that it can affect the development of AD, by skewing the immune response away from an allergic phenotype. In this study, a mouse model to study the effect of dietary compounds on the development and treatment of food allergy-induced AD will be set-up. For this model, BALB/c mice are orally sensitized with ovalbumin (OVA; generally used to induce hen’s egg allergy) plus cholera toxin adjuvant once a week, for 5 consecutive weeks. One week after the last sensitization, the mouse skin will be challenged with OVA on tape-stripped back skin. This is repeated 3 days later, and again 4 days later, the mice are sacrificed. Outcome parameters as skin thickness, inflammatory cell influx and skin mucosal cytokine levels will be studied. Following development of the AD model the effect of dietary intenvention with a combination of specific OS and TLR ligands will be evaluated on the different outcome parameters.

In 20 patients with pure menstrual migraine either Estraderm TTS 50 patches (E) or placebo (P) patches were applied during three successive menstrual cycles, randomly allocated to the treatment sequences E-P-E or P-E-P. Clinical neurophysiological tests, contingent negative variation (CNV) and exteroceptive temporalis muscle suppression test (ETST) were performed before treatment. The predictive value of these tests regarding the efficacy of Estraderm TTS was studied. Neither the number, duration and severity of the migraine attacks, nor the consumption of analgesics and ergotamine differed significantly during Estraderm TTS and placebo treatment. The ETST was consistent with migraine in 35% (95% confidence interval 15.4 to 59.2) of the patients. The CNV in 55% (31.5 to 76.9), and both tests in 25% (8.7 to 49.1%). Regarding the prediction of the Estraderm TTS effect on the migraine attacks, the specificity of the ETST, CNV and the combination of ETST with CNV, calculated for the first two cycles, was respectively 81.8% (48.2 to 97.7), 45.5% (16.8 to 76.6) and 80% (28.4 to 99.5). For the last two cycles these values were respectively 75% (42.8 to 94.5), 50.0% (21.1 to 87.9) and 71.4% (29.0 to 96.3). The sensitivity of the tests was respectively 62.5% (24.5 to 91.5), 62.5% (24.5 to 91.5) and 66.7% (22.3 to 95.7) in the first 2 cycles. In the last 2 cycles 50.0% (15.1 to 84.3), 62.5% (24.5 to 91.5) and 60% (14.7 to 94.7). This study did not demonstrate an effectiveness of Estraderm TTS in perimenstrual migraine, except for the subgroup of perimenstrual migraine patients in whom the ETST test results were consistent with migraine.