Bacterial meningitis: Mechanisms of disease and therapy

Bacterial meningitis continues to be a serious infectious disease with a high morbidity and mortality in young children. Early recognition and initiation of adequate treatment are the major determinants for a good outcome. Recent advances in our understanding of the host inflammatory response by cytokines may result in the use of new therapeutic strategies. Such modulation of the inflammatory response may reduce the incidence of sequelae and death. The use of steroids as adjunctive therapy in children with bacterial meningitis probably has beneficial effects although the available data are still controversial. Additionally, studies in experimental meningitis models indicate that non-steroidal anti-inflammatory drugs and monoclonal antibodies against bacterial products, cytokines and CD18 on leucocytes reduce the extent of the meningeal inflammation. Human studies to evaluate the efficacy of these immune modulators are expected to start soon. However, prevention of bacterial meningitis by conjugate vaccines againstStreptococcus pneumoniae andNeisseria meningitidis will be the most promising development in the next decade

Glafenine-associated anaphylaxis as a cause of hospital admission in The Netherlands

Summary. In 1981 generalized anaphylaxis was registered on 166 occasions in Dutch general an

Bench-to-bedside review: genetic influences on meningococcal disease

This review discusses the possible involvement of a variety of genetic polymorphisms on the course of meningococcal disease. It has been shown that several common genetic polymorphisms can either influence the susceptibility to meningococcal disease or can account for a higher mortality rate in patients. Gene polymorphisms concerning antibody receptors, lipopolysaccharide (LPS) binding receptors or proteins, innate complement proteins as well as cytokines and hemostatic proteins are described. The study of genetic polymorphisms might provide important insights in the pathogenesis of meningococcal disease and could make it possible to identify individuals who are at risk of either contracting or dying from meningococcal disease

Correlated evolution of nucleotide substitution rates and allelic variation in Mhc-DRB lineages of primates

<p>Abstract</p> <p>Background</p> <p>The major histocompatibility complex (MHC) is a key model of genetic polymorphism. Selection pressure by pathogens or other microevolutionary forces may result in a high rate of non-synonymous substitutions at the codons specifying the contact residues of the antigen binding sites (ABS), and the maintenance of extreme MHC allelic variation at the population/species level. Therefore, selection forces favouring MHC variability for any reason should cause a correlated evolution between substitution rates and allelic polymorphism. To investigate this prediction, we characterised nucleotide substitution rates and allelic polymorphism (i.e. the number of alleles detected in relation to the number of animals screened) of several <it>Mhc </it>class II <it>DRB </it>lineages in 46 primate species, and tested for a correlation between them.</p> <p>Results</p> <p>First, we demonstrate that species-specific and lineage-specific evolutionary constraints favour species- and lineage-dependent substitution rate at the codons specifying the ABS contact residues (i.e. certain species and lineages can be characterised by high substitution rate, while others have low rate). Second, we show that although the degree of the non-synonymous substitution rate at the ABS contact residues was systematically higher than the degree of the synonymous substitution rate, these estimates were strongly correlated when we controlled for species-specific and lineage-specific effects, and also for the fact that different studies relied on different sample size. Such relationships between substitution rates of different types could even be extended to the non-contact residues of the molecule. Third, we provide statistical evidence that increased substitution rate along a MHC gene may lead to allelic variation, as a high substitution rate can be observed in those lineages in which many alleles are maintained. Fourth, we show that the detected patterns were independent of phylogenetic constraints. When we used phylogenetic models that control for similarity between species, due to common descent, and focused on variations within a single lineage (<it>DRB1*03</it>), the positive relationship between different substitution rates and allelic polymorphisms was still robust. Finally, we found the same effects to emerge in the analyses that eliminated within-species variation in MHC traits by using strictly single population-level studies. However, in a set of contrasting analyses, in which we focused on the non-functional <it>DRB6 </it>locus, the correlation between substitution rates and allelic variation was not prevalent.</p> <p>Conclusion</p> <p>Our results indicate that positive selection for the generation of allelic polymorphism acting on the functional part of the protein has consequences for the nucleotide substitution rate along the whole exon 2 sequence of the <it>Mhc-DRB </it>gene. Additionally, we proved that an increased substitution rate can promote allelic variation within lineages. Consequently, the evolution of different characteristics of genetic polymorphism is not independent.</p

Electronic transport coefficients from ab initio simulations and application to dense liquid hydrogen

Using Kubo's linear response theory, we derive expressions for the frequency-dependent electrical conductivity (Kubo-Greenwood formula), thermopower, and thermal conductivity in a strongly correlated electron system. These are evaluated within ab initio molecular dynamics simulations in order to study the thermoelectric transport coefficients in dense liquid hydrogen, especially near the nonmetal-to-metal transition region. We also observe significant deviations from the widely used Wiedemann-Franz law which is strictly valid only for degenerate systems and give an estimate for its valid scope of application towards lower densities

Molecular epidemiology of penicillin-nonsusceptible Streptococcus pneumoniae among children in Greece

A total of 145 penicillin-nonsusceptible Streptococcus pneumoniae strains were isolated from young carriers in Greece and analyzed by antibiotic susceptibility testing, serotyping, restriction fragment end labeling (RFEL), and penicillin-binding protein (PBP) genotyping. The serotypes 23A and 23F (54%), 19A and 19F (25%), 9V (5%), 15A, 15B, and 15C (4%), 6A and 6B (4%), and 21 (4%) were most prevalent in this collection. Fifty-three distinct RFEL types were identified. Sixteen different RFEL clusters, harboring 2 to 32 strains each, accounted for 82% of all strains. Eight of these genetic clusters representing 60% of the strains were previously identified in other countries. A predominant lineage of 66 strains (46%) harboring five RFEL types and the serotypes 19F and 23F was closely related to the pandemic clone Spain(23F)-1 (genetic relatedness of > or =85%). Another lineage, representing 11 strains, showed close genetic relatedness to the pandemic clone France(9V)-3. Another lineage of 8 serotype 21 strains was Greece specific since the RFEL types were not observed in an international collection of 193 genotypes from 16 different countries. Characterization of the PBP genes pbp1a, pbp2b, and pbp2x revealed 20 distinct PBP genotypes of which PBP type 1-1-1, initially observed in the pandemic clones 23F and 9V, was predominantly present in 11 RFEL types in this Greek collection of penicillin-nonsusceptible strains (55%). Sixteen PBP types covering 52 strains (36%) were Greece specific. This study underlines the strong contribution of penicillin-resistant international clones to the prevalence and spread of penicillin-nonsusceptible pneumococci among young children in Greece