Doppler ultrasound in the measurement of pulse wave velocity: agreement with the Complior method

Aortic stiffness is an independent predictor factor for cardiovascular risk. Different methods for determining pulse wave velocity (PWV) are used, among which the most common are mechanical methods such as SphygmoCor or Complior, which require specific devices and are limited by technical difficulty in obtaining measurements. Doppler guided by 2D ultrasound is a good alternative to these methods. We studied 40 patients (29 male, aged 21 to 82 years) comparing the Complior method with Doppler. Agreement of both devices was high (R = 0.91, 0.84-0.95, 95% CI). The reproducibility analysis revealed no intra-nor interobserver differences. Based on these results, we conclude that Doppler ultrasound is a reliable and reproducible alternative to other established methods for themeasurement of aortic PWV

Chirurgie [Trends in surgery]

More than the number of real novelties, trends and preliminary results characterise the annual development in surgery. The wealth and diversity of topics to be covered require arbitrary choices, therefore not necessarily complete. The constant development of choledocolithiasis management, dominated by minimal invasive technology, treatments of unusual nature of two frequent proctological conditions, fistulae and haemorrhoids, the increasing importance of metabolic bariatric surgery, as well as the strict rules of effective melanoma treatment, represent as many directions in which the operating procedure, although unseen, continue to gain quality and security.

Prise en charge des jeunes patients avec endocrinopathies pediatriques chroniques: les défis d'une transition souvent difficile [Caring for patients with pediatric endocrinopathies and diabetes into adulthood: challenges of an often difficult transition].

The success of therapies for a number of pediatric disorders has posed new challenges for the long-term follow-up of adolescents with chronic endocrinopathies. Unfortunately, too many patients are lost during the transfer from pediatric to adult clinics. The transition process should be well-organized and include the young person and family. Recognizing the special needs of these adolescents is an important step in developing patient-centered approaches to care that enable patients to develop autonomy and self care skills. Key elements in this process include structured policies and guidelines, communication and close collaboration between pediatric and adult clinics, and integrating nurse clinicians in the transition process to help close the gaps in care.

Immunosuppresseurs: usages systémiques et neurologiques [Systemic and neurological uses of immunosuppressive agents].

Involvement of the central or peripheral nervous system, frequently present in systemic inflammatory immune disorders, has to be considered a severe threat and requires aggressive immunosuppressive treatment to achieve rapid remission. This is usually obtained with high-dose systemic corticosteroids combined with cyclophosphamide. Once remission is obtained, immunosuppressive agents with a more favorable safety profile are needed to exert a corticosteroid-sparing effect and minimize adverse events. New therapeutic approaches are currently developed to treat autoimmune diseases, mostly linked to the definition of new indications for biological agents such as TNF-alpha antagonists and rituximab.

Transcriptional and functional profiles of voltage-gated Na(+) channels in injured and non-injured DRG neurons in the SNI model of neuropathic pain.

Changes in expression and function of voltage-gated sodium channels (VGSC) in dorsal root ganglion (DRG) neurons may play a major role in the genesis of peripheral hyperexcitability that occurs in neuropathic pain. We present here the first description of changes induced by spared nerve injury (SNI) to Na(v)1 mRNA levels and tetrodotoxin-sensitive and -resistant (TTX-S/TTX-R) Na(+) currents in injured and adjacent non-injured small DRG neurons. VGSC transcripts were down-regulated in injured neurons except for Na(v)1.3, which increased, while they were either unchanged or increased in non-injured neurons. TTX-R current densities were reduced in injured neurons and the voltage dependence of steady-state inactivation for TTX-R was positively shifted in injured and non-injured neurons. TTX-S current densities were not affected by SNI, while the rate of recovery from inactivation was accelerated in injured neurons. Our results describe altered neuronal electrogenesis following SNI that is likely induced by a complex regulation of VGSCs.

Chemotherapy-induced peripheral neuropathies: an integrative review of the literature

OBJECTIVE: To identify scientific studies and to deepen the knowledge of peripheral neuropathies induced by chemotherapy antineoplastic, seeking evidence for assistance to cancer patients. METHOD: Integrative review of the literature conducted in the databases Latin American and Caribbean Health Sciences (LILACS), Scientific Electronic Library Online (SciELO), Medical Literature Analysis (PubMed/MEDLINE), the Cochrane Library and the Spanish Bibliographic Index Health Sciences (IBECS). RESULTS: The sample consisted of 15 studies published between 2005-2014 that met the inclusion criteria. Studies showed aspects related to advanced age, main symptoms of neuropathy and chemotherapy agents as important adverse effect of neuropathy. CONCLUSION: We identified a small number of studies that addressed the topic, as well as low production of evidence related to interventions with positive results. It is considered important to develop new studies proposed for the prevention and/or treatment, enabling adjustment of the patient's cancer chemotherapy and consequently better service.

The expansion of 300 CTG repeats in myotonic dystrophy transgenic mice does not induce sensory or motor neuropathy.

Although many studies have been carried out to verify the involvement of the peripheral nervous system (PNS) in dystrophia myotonica (DM1) patients, the results remain controversial. The generation of DM1 transgenic mice displaying the human DM1 phenotype provides a useful tool to investigate the type and incidence of structural abnormalities in the PNS. In the present study, the morphological and morphometric analysis of semi-thin sections of sciatic and sural nerves, lumbar dorsal root ganglia (DRG) and lumbar spinal cords revealed that in DM1 transgenic mice carrying 300 CTG repeats, there is no change in the number and diameter of myelinated axons compared to wild type. Only a non-significant reduction in the percentage of thin myelinated axons was detected in electron micrographs of ultra-thin sciatic nerve sections. Analysis of the number of neurons did not reveal a loss in number of either sensory neurons in the lumbar DRG or motor neurons in the lumbar spinal cord in these DM1 mice. Furthermore, in hind limb muscle sections, stained with a neurofilament antibody and alpha-bungarotoxin, the intramuscular axon arborization appeared normal in DM1 mice and undistinguishable from that in wild-type mice. Moreover, in DM1 mice, there was no irregularity in the structure or an increase in the endplate area. Also statistical analysis did not show an increase in endplate density or in the concentration of acetylcholine receptors. Altogether, these results suggest that 300 CTG repeats are not sufficient to induce axonopathy, demyelination or neuronopathies in this transgenic mouse model.

Lentiviral vectors: a powerful tool to target astrocytes in vivo.

The morphological and functional diversity of astrocytes, and their essential contribution in physiological and pathological conditions, are starting to emerge. However, experimental systems to investigate neuron-glia interactions and develop innovative approaches for the treatment of central nervous system (CNS) disorders are still very limited. Fluorescent reporter genes have been used to visualize populations of astrocytes and produce an atlas of gene expression in the brain. Knock-down or knock-out of astrocytic proteins using transgenesis have also been developed, but these techniques remain complex and time-consuming. Viral vectors have been developed to overexpress or silence genes of interest as they can be used for both in vitro and in vivo studies in adult mammalian species. In most cases, high transduction efficiency and long-term transgene expression are observed in neurons but there is limited expression in astrocytes. Several strategies have been developed to shift the tropism of lentiviral vectors (LV) and allow local and controlled gene expression in glial cells. In this review, we describe how modifications of the interaction between the LV envelope glycoprotein and the surface receptor molecules on target cells, or the integration of cell-specific promoters and miRNA post-transcriptional regulatory elements have been used to selectively express transgenes in astrocytes.

Neuropathies périphériques d'origine médicamenteuse [Drug-induced peripheral neuropathy].

Drug-induced peripheral neuropathies are common, secondary to multiple drug classes, in particular chemotherapeutic agents. They have an important impact on patients' quality of life. In recent years, significant progress has been made in the understanding of some pathophysiological mechanisms. The use of more objective assessment tools should allow the development of individualized and more effective therapeutic strategies.

Conditional BDNF release under pathological conditions improves Huntington's disease pathology by delaying neuronal dysfunction

Background Brain-Derived Neurotrophic Factor (BDNF) is the main candidate for neuroprotective therapy for Huntington's disease (HD), but its conditional administration is one of its most challenging problems. Results Here we used transgenic mice that over-express BDNF under the control of the Glial Fibrillary Acidic Protein (GFAP) promoter (pGFAP-BDNF mice) to test whether up-regulation and release of BDNF, dependent on astrogliosis, could be protective in HD. Thus, we cross-mated pGFAP-BDNF mice with R6/2 mice to generate a double-mutant mouse with mutant huntingtin protein and with a conditional over-expression of BDNF, only under pathological conditions. In these R6/2:pGFAP-BDNF animals, the decrease in striatal BDNF levels induced by mutant huntingtin was prevented in comparison to R6/2 animals at 12 weeks of age. The recovery of the neurotrophin levels in R6/2:pGFAP-BDNF mice correlated with an improvement in several motor coordination tasks and with a significant delay in anxiety and clasping alterations. Therefore, we next examined a possible improvement in cortico-striatal connectivity in R62:pGFAP-BDNF mice. Interestingly, we found that the over-expression of BDNF prevented the decrease of cortico-striatal presynaptic (VGLUT1) and postsynaptic (PSD-95) markers in the R6/2:pGFAP-BDNF striatum. Electrophysiological studies also showed that basal synaptic transmission and synaptic fatigue both improved in R6/2:pGAP-BDNF mice. Conclusions These results indicate that the conditional administration of BDNF under the GFAP promoter could become a therapeutic strategy for HD due to its positive effects on synaptic plasticity.