Long-term complications and risk of other serious infections following invasive Haemophilus influenzae serotype b disease in vaccinated children

This study describes the long-term complications in children with Haemophilus influenzae serotype b (Hib) vaccine failure and to determine their risk of other serious infections. The families of 323 children with invasive Hib disease after appropriate vaccination (i.e. vaccine failure) were contacted to complete a questionnaire relating to their health and 260 (80.5%) completed the questionnaire. Of the 124 children with meningitis, 18.5% reported serious long-term sequelae and a further 12.1% of parents attributed other problems to Hib meningitis. Overall, 14% (32/231 cases) of otherwise healthy children and 59% (17/29 cases) of children with an underlying condition developed at least one other serious infection requiring hospital admission. In a Poisson regression model, the risk of another serious infection was independently associated with the presence of an underlying medical condition (incidence risk ratio (IRR) 7.6, 95% CI 4.8–12.1; p < 0.0001), both parents having had a serious infection (IRR 4.1, 95% CI 1.6–10.3; p = 0.003), requirement of more than two antibiotic courses per year (IRR 2.3, 95% CI 1.4–3.6; p = 0.001) and the presence of a long-term complication after Hib infection (IRR 1.8, 95% CI 1.1–3.1; p = 0.03). Thus, rates of long-term sequelae in children with vaccine failure who developed Hib meningitis are similar to those in unvaccinated children in the pre-vaccine era. One in seven otherwise healthy children (14%) with Hib vaccine failure will go on to suffer another serious infection requiring hospital admission in childhood, which is higher than would be expected for the UK paediatric population.     

Antiepileptic drugs in development

BACKGROUND: Despite the success of several new antiepileptic drugs, about one third of patients with epilepsy are not seizure free on medication. Improvement in this situation might lie in drugs that are currently in development. RECENT DEVELOPMENTS: Some new antiepileptic drugs are modifications of those already available, referred to in this Rapid Review as evolutionary drugs. These modifications of existing drugs are developed to improve effectiveness, often by increasing tolerability. Other drugs work by new mechanisms and are usually discovered through screening of animal models. WHERE NEXT? The large number of drugs currently in clinical trials provides a measure of hope for patients whose epilepsy is not controlled with currently available medication. In the future, this range of antiepileptic drugs will probably increase because of the use of new animal models, discovery of new basic mechanisms of epileptogenesis, acceleration of proof of principle studies in people, and development of new methods of drug delivery.     

Anodal motor cortex stimulation paired with movement repetition increases anterograde interference but not savings

Retention of motor adaptation is evident in savings, where initial learning improves subsequent learning, and anterograde interference, where initial learning impairs subsequent learning. Previously, we proposed that use‐dependent movement biases induced by movement repetition contribute to anterograde interference, but not to savings. Here, we evaluate this proposal by limiting or extending movement repetition while stimulating the motor cortex (M1) with anodal transcranial direct current stimulation (tDCS), a brain stimulation technique known to increase use‐dependent plasticity when applied during movement repetition. Participants first adapted to a counterclockwise rotation of visual feedback imposed either abruptly (extended repetition) or gradually (limited repetition) in a first block (A1), during which either sham or anodal tDCS (2 mA) was applied over M1. Anterograde interference was then assessed in a second block (B) with a clockwise rotation, and savings in a third block (A2) with a counterclockwise rotation. Anodal M1 tDCS elicited more anterograde interference than sham stimulation with extended but not with limited movement repetition. Conversely, anodal M1 tDCS did not affect savings with either limited or extended repetition of the adapted movement. Crucially, the effect of anodal M1 tDCS on anterograde interference did not require large errors evoked by an abrupt perturbation schedule, as anodal M1 tDCS combined with extended movement repetition within a gradual perturbation schedule similarly increased anterograde interference but not savings. These findings demonstrate that use‐dependent plasticity contributes to anterograde interference but not to savings.     

aFGF, bFGF and flg mRNAs Show Distinct Patterns of Induction in the Hippocampus Following Kainate-induced Seizures

We report that kainic acid-induced seizures lead to marked increases in mRNAs encoding basic and acidic fibroblast growth factors (bFGF and aFGF, respectively) and fig, one of their receptors, in the rat hippocampus. Anticonvulsant pretreatment inhibits the up-regulation of these mRNAs. The observed increase in fig mRNA levels involves the pyramidal cells of all hippocampal subfields and the granular ceils of the dentate gyrus. The increased expression of aFGF and bFGF mRNAs is limited to neuron populations that are resistant to seizure-induced injury, the granular cells of dentate gyrus and pyramidal cells of CA1 region, respectively. The results suggest that the increase in the FGFs and fig may play pivotal roles in neuron survival and in long-term changes occurring in the hippocampus following seizure activity.     

Oral Absorption of D-Oligopeptides in Rats via the Paracellular Route

Purpose. This study was undertaken to examine the structural determinants of oral bioavailability in the rat of a set of oligopeptides comprising D-amino acids, which were taken to be absorbed paracellularly based on a pronounced sensitivity of permeability to electrical resistance in Caco-2 cell monolayers. Methods. The study series comprised eleven D-oligopeptides, designed not to be recognised by peptidases or transport proteins, and to have molecular weights between 222 and 406 daltons with different net electrical charges and composition of D-amino acids. All the peptides were [³H]-radiolabelled and analyzed by HPLC with radiometric detection. Bioavailability was estimated based on 24-hr urinary excretion of unchanged peptide after oral and intravenous administrations. Results. As expected, the series proved metabolically stable. Bioavailability was independent of oral dose when varied by a factor of 10,000, suggesting passive absorption. Whereas bioavailability decreased sharply from 30% to 1% with increasing molecular weight, net charge showed little, if any, effect on bioavailabilty. Conclusions. This D-oligopeptide model series served as a useful probe for the structural requirements for paracellular absorption in vivo. A critical determinant of bioavailability is molecular size, expressed as molecular weight in this study; net charged appeared of much lesser importance.