Immune response to capsular polysaccharide and surface proteins of Streptococcus pneumoniae in patients with invasive pneumococcal disease

The immune response to pneumococcal capsular polysaccharides (CPSs) and to the pneumococcal surface proteins cell wall-associated serine proteinase A (PrtA), pneumococcal surface protein A (PspA), and Streptococcus pneumoniae pullulanase A was evaluated in 45 patients with invasive pneumococcal disease compared with healthy adults. In serum from patients with meningitis and pneumonia, CPS antibody levels were low, compared with healthy adults; antibody levels did not differ between groups and did not change between phases. Levels of immunoglobulin G directed against the investigated pneumococcal surface proteins in patients with invasive pneumococcal disease were in the same range as in healthy adults. However, median PrtA and PspA antibody levels tended to increase during early convalescent phase. Low levels of CPS antibody, rather than of antibodies directed against the pneumococcal surface proteins, may predispose to invasive pneumococcal infection.     

Controversies and open questions in the definitions and classification of the hypereosinophilic syndromes and eosinophilic leukemias

Eosinophilia is frequently detectable in certain myeloid neoplasms and various reactive conditions, but it may also occur in the absence of an apparent underlying disease, or, rarely, as a paraneoplastic feature with solid tumors. In myeloid neoplasms, eosinophils are considered to belong to the malignant clone in most cases, whereas in all other conditions, eosinophilia is a reactive process triggered by eosinopoietic cytokines. Excessive accumulation of eosinophils, also termed hypereosinophilia (HE), is typically seen in eosinophilic leukemias, but it may also occur in other neoplasms and reactive disorders. HE-related end organ damage may develop in patients with reactive HE but also in those with hematologic malignancies. During the past few years, our knowledge about HE and HE-related organ damage in hematologic and nonhematologic disorders has improved considerably. Moreover, proposals for the definition and classification of eosinophil disorders have been generated by various expert groups and by the World Health Organization (WHO). However, several questions related to eosinophils and HE remain open, and many aspects of the definition and classification of eosinophil disorders and related pathologies remain controversial. In the current article, these open issues are discussed with special reference to the 2008 WHO classification of myeloid neoplasms and other classifications proposed by immunologists and various expert panels, as well as definitions and criteria recently proposed in a multidisciplinary consensus proposal.     

Bimanual Recoupling by Visual Cueing in Callosal Disconnection

Abstract

The cerebral control of bimanual movements is not completely understood. We investigated a 59-year-old, right-handed man who presented with an acute bimanual coordination deficit. Magnetic resonance imaging showed a lesion involving the entire corpus callosum, which was found on stereotactic biopsy to be an ischemic infarct. Paired-pulse transcranial magnetic stimulation indicated that the patient had a lack of interhemispheric inhibition, while intracortical inhibition in motor cortex of either side was normal. Functional magnetic resonance imaging showed activation of the left SMA, the bilateral motor cortex and anterior cerebellum during spontaneous bimanual thumb-index oppositions, which were uncoupled as evident from simultaneous electromyographic recordings. In contrast, when the bimanual thumb-index oppositions were cued by a visual stimulus, the movements of both hands were tightly correlated. This synchronized activity was accompanied by additional activations bilateral in lateral occipital cortex, dorsal premotor cortex and cerebellum. The data suggest that the visually cued movements of both hands were recoupled by action of a bihemispheric motor network.     

Use of Imatinib in the Prevention of Heterotopic Ossification

Background

Heterotopic ossification (HO) is a common complication following orthopedic and trauma surgery, which may have substantial negative effects on the postoperative outcome. Angiogenesis appears to play a critical role in heterotopic ossification. One of the involved signaling molecules is platelet-derived growth factor (PDGF) which may be inhibited by imatinib.

Questions/Purposes

Our goal was to prevent HO by pharmacologically interfering with the molecular signaling pathways involved in the developmental process. We hypothesized that by administering a proven inhibitor of PDGF expression, heterotopic bone formation may be prevented.

Methods

The effect of imatinib on HO formation was studied in a murine model which reliably produces islets of HO within the soft tissue following Achilles tenotomy. The control group underwent Achilles tenotomy only. The imatinib group received imatinib mesylate. After trial completion, the limbs were harvested and scanned by micro-CT. Heterotopic bone volume was then identified and quantified.

Results

The mean volume of heterotopic bone formed in the control group was 0.976mm³ compared to 0.221 mm³ in the imatinib group. The volume of HO in the treatment group was reduced by 85% compared to the control group.

Conclusions

The administration of imatinib was associated with a significantly reduced volume of HO. This may be due to the inhibitory effect of imatinib on the PDGF signaling pathway during development of HO.

Clinical Relevance

The successful reduction of HO formation following imatinib administration has led to further insight concerning the pathogenesis of HO which in the future may lead to new clinical approaches towards the prevention of HO.

Electronic supplementary material

The online version of this article (doi:10.1007/s11420-013-9335-y) contains supplementary material, which is available to authorized users.