Discectomía cervical anterior y artrodesis con caja intersomática de titanio: experiencia clínica con 272 casos

El present estudi revisa l’experiència clínica quirúrgica en el servei de neurocirurgia de l’hospital universitari de Bellvitge amb 272 pacients sotmesos a discectomia cervical anterior i artrodesi amb caixa intersomàtica de titani per patologia degenerativa discal. Es revisen els resultats clínics, radiològics i les complicacions presentades. S’obtenen a l’any de la intervenció, resultats clínics excel•lents o bons en un 68.25 % dels pacients, una alta taxa de fusió cervical (97.34 %) i un baix índex de complicacions operatòries (4.41 %)

Distribution and genesis of the RFRP-producing neurons in the rat brain: comparison with melanin-concentrating hormone- and hypocretin-containing neurons.

Prepro-RFRP-containing neurons have recently been described in the mammalian brain. These neurons are only found in the tuberal hypothalamus. In this work, we have provided a detailed analysis of the distribution of cells expressing the RFRP mRNA, and found them in seven anatomical structures of the tuberal hypothalamus. No co-expression with melanin-concentrating hormone (MCH) or hypocretin (Hcrt), that are also described in neurons of the tuberal hypothalamus, was observed. Using the BrdU method, we found that all RFRP cell bodies are generated between E13 and E14. Thus, RFRP neurons form a specific cell population with a complex distribution pattern in the tuberal hypothalamus. However, they are generated in one peak. These observations are discussed with data concerning the distribution and genesis of the MCH and Hcrt cell populations that are also distributed in the tuberal hypothalamus.

Repair of non-circumferential cervical trachea defects by three different latissimus dorsi flaps. A comparative studyin an experimental setting.

BACKGROUND: Large intrathoracic airway defects may be closed using a pedicled latissimus dorsi (LD) flap, with rewarding results. This study addresses the question of whether this holds true for extrathoracic non-circumferential tracheal defects. METHODS: A cervical segment of the trachea of 4 x 1 cm was resected in 9 white male pigs. The defect was stented with a silicone stent for 3 months and closed either by an LD flap alone (group a, n = 3), an LD flap with an attached rib segment covered by pleura (group b, n = 3), or an LD flap reinforced by a perforated polylactide (MacroPore) plate (group c, n = 3). The trachea was assessed by rigid endoscopy at 3 and 4 months and histologically at 4 months postoperatively. RESULTS: The degree of stenosis at the level of the reconstruction at 4 months was 25, 50 and 75% in group a, 15, 50 and 60% in group b, and 20, 95 and 95% in group c, respectively. The percentage of the defect covered by columnar epithelium was 100% in all animals of group a, 60, 100 and 100% in group b, and 10, 0 and 0% in group c. Resorption of the rib was seen in all animals of group b and obstructive inflammatory polyps were found in 2 animals of group c. CONCLUSION: Pedicled LD flaps provided less satisfactory results for closure of large non-circumferential extrathoracic airway defects than observed after intrathoracic reconstruction. A pedicled rib segment added to the LD flap did not improve the results obtained from LD flap repair alone, and an embedded MacroPore prosthesis may result in severe airway stenosis due to plate migration and intense inflammatory reaction protruding into the tracheal lumen.

Brain-derived neurotrophic factor enhances the expression of the monocarboxylate transporter 2 through translational activation in mouse cultured cortical neurons.

MCT2 is the predominant neuronal monocarboxylate transporter allowing lactate use as an alternative energy substrate. It is suggested that MCT2 is upregulated to meet enhanced energy demands after modifications in synaptic transmission. Brain-derived neurotrophic factor (BDNF), a promoter of synaptic plasticity, significantly increased MCT2 protein expression in cultured cortical neurons (as shown by immunocytochemistry and western blot) through a translational regulation at the synaptic level. Brain-derived neurotrophic factor can cause translational activation through different signaling pathways. Western blot analyses showed that p44/p42 mitogen-activated protein kinase (MAPK), Akt, and S6 were strongly phosphorylated on BDNF treatment. To determine by which signal transduction pathway(s) BDNF mediates its upregulation of MCT2 protein expression, the effect of specific inhibitors for p38 MAPK, phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK), p44/p42 MAPK (ERK), and Janus kinase 2 (JAK2) was evaluated. It could be observed that the BDNF-induced increase in MCT2 protein expression was almost completely blocked by all inhibitors, except for JAK2. These data indicate that BDNF induces an increase in neuronal MCT2 protein expression by a mechanism involving a concomitant stimulation of PI3K/Akt/mTOR/S6, p38 MAPK, and p44/p42 MAPK. Moreover, our observations suggest that changes in MCT2 expression could participate in the process of synaptic plasticity induced by BDNF.

Role of the JNK pathway in NMDA-mediated excitotoxicity of cortical neurons.

Excitotoxic insults induce c-Jun N-terminal kinase (JNK) activation, which leads to neuronal death and contributes to many neurological conditions such as cerebral ischemia and neurodegenerative disorders. The action of JNK can be inhibited by the D-retro-inverso form of JNK inhibitor peptide (D-JNKI1), which totally prevents death induced by N-methyl-D-aspartate (NMDA) in vitro and strongly protects against different in vivo paradigms of excitotoxicity. To obtain optimal neuroprotection, it is imperative to elucidate the prosurvival action of D-JNKI1 and the death pathways that it inhibits. In cortical neuronal cultures, we first investigate the pathways by which NMDA induces JNK activation and show a rapid and selective phosphorylation of mitogen-activated protein kinase kinase 7 (MKK7), whereas the only other known JNK activator, mitogen-activated protein kinase kinase 4 (MKK4), was unaffected. We then analyze the action of D-JNKI1 on four JNK targets containing a JNK-binding domain: MAPK-activating death domain-containing protein/differentially expressed in normal and neoplastic cells (MADD/DENN), MKK7, MKK4 and JNK-interacting protein-1 (IB1/JIP-1).

Characterization of Nedd4-2 ubiquitin ligase expression in experimental neuropathic pain

Background: Neuropathic pain is associated with altered expression of voltage-gated sodium channels (VGSCs). The ubiquitin ligase Nedd4-2 regulates sodium channels and we have previously demonstrated in expression systems that this protein decreases the Nav1.7 current. Nav1.7 is the most abundant VGSC in dorsal root ganglion (DRG) and is a major contributor to pain perception. We hypothesize that Nedd4-2 modulates Nav1.7 channel density at the neuronal cell membrane and the goal of this present experiment is to characterize Nav1.7 and Nedd4-2 expression in the context of neuropathic pain. Methods: Biotinylation, Western Blot and Immunohistochemistry experiments for Nav1.7 and Nedd4-2 were performed in HEK transfected cells or in rodent DRGs 7 days after SNI surgery. We used antibodies against Nedd4-2 and Nav1.7 and several comarkers of DRG neurons (Peripherin for nociceptors, NF-200 for large myelinated cells, ATF3 for injured neurons). Data are expressed in proportion of positive cells (%) and protein signal ratio } SEM, n = 3-4 in each condition. Results: In HEK293 cells, upon co-expression of Nedd4-2, a decrease of 50% of Nav1.7 signal at the membrane is demonstrated (p ≤0.005). Immunofluorescence on DRGs neurons reveals a decreased number of positive Nedd4-2 cells in the SNI model (27.0 } 1.2%) versus sham group (43.4 } 3.5%) (p <0.005). Nedd4-2 is mainly colocalized with markers of small neurons and almost absent in large neurons. In addition, Nedd4-2 is predominantly decreased in injured ATF3 positive cells. Conclusion: Our results indicate that Nedd4-2 decreases Nav1.7 channels and currents at the cell membrane and that it is mainly expressed in nociceptors and downregulated after nerve injury. Taken together, our data suggest that the reduction of Nedd4-2, after nerve injury, modulates Nav1.7 activity and can contribute to neuropathic pain. We will further try to restore a normal level of Nedd4.2 via a gene therapy approach with viral vectors in order to soothe symptoms of neuropathic pain.

Multilevel oblique corpectomy for cervical spondylotic myelopathy preserves segmental motion.

PURPOSE: To document the neurological outcome, spinal alignment and segmental range of movement after oblique cervical corpectomy (OCC) for cervical compressive myelopathy. METHODS: This retrospective study included 109 patients--93 with cervical spondylotic myelopathy and 16 with ossified posterior longitudinal ligament in whom spinal curvature and range of segmental movements were assessed on neutral and dynamic cervical radiographs. Neurological function was measured by Nurick's grade and modified Japanese Orthopedic Association (JOA) scores. Eighty-eight patients (81%) underwent either a single- or two-level corpectomy; the remaining (19%) undergoing three- or four-level corpectomies. The average duration of follow-up was 30.52 months. RESULTS: The Nurick's grade and the JOA scores showed statistically significant improvements after surgery (p < 0.001). The mean postoperative segmental angle in the neutral position straightened by 4.7 ± 6.5°. The residual segmental range of movement for a single-level corpectomy was 16.7° (59.7% of the preoperative value), for two-level corpectomy it was 20.0° (67.2%) and for three-level corpectomies it was 22.9° (74.3%). 63% of patients with lordotic spines continued to have lordosis postoperatively while only one became kyphotic without clinical worsening. Four patients with preoperative kyphotic spines showed no change in spine curvature. None developed spinal instability. CONCLUSIONS: The OCC preserves segmental motion in the short-term, however, the tendency towards straightening of the spine, albeit without clinical worsening, warrants serial follow-up imaging to determine whether this motion preservation is long lasting.

Gonadotropin-releasing hormone secretion from hypothalamic neurons: stimulation by insulin and potentiation by leptin.

Insulin and leptin are peripheral metabolic factors signaling the body needs in energy to the central nervous system. Because energy homeostasis and reproductive function are closely related phenomena, we investigated the respective roles played by insulin and leptin in the hypothalamic control of GnRH secretion. We observed that increasing circulating insulin levels, by performing hyperinsulinemic clamp studies in male mice, was associated with a significant rise in LH secretion. This effect of insulin is likely mediated at the hypothalamic level, because it was also found to stimulate the secretion and the expression of GnRH by hypothalamic neurons in culture. Leptin was found to potentiate the effect of insulin on GnRH secretion in vitro but was devoid of any effect on its own. These data represent the first evidence of direct insulin sensing by hypothalamic neurons involved in activating the neuroendocrine gonadotrope axis. They also demonstrate that these neurons can integrate different hormonal signals to modulate net hypothalamic GnRH output. We propose that such integration is an essential mechanism for the adaptation of reproductive function to changes in the metabolic status of an individual.

Alteraciones posturográficas en fases agudas del latigazo cervical.

L’objectiu del treball és evidenciar l’existència d’alteracions posturogràfiques en la primera fase posterior a l’accident. Es realitzà un estudi prospectiu a 14 pacients utilitzant una plataforma dinamomètrica fixa. Predominà el sexe femení (79.9%) amb edat mitja de 29 anys. La mitjana del temps fins realitzar la valoració fou de 14 hores. Obtenim un patró de disfunció somatosensorial en 7 pacients (50%), 2 presentaren disfunció vestibular i 5 patró normal o compensat. La prova Romberg d’ulls tancats s’observaren les majors diferències. Conclusions : La postugrafia permet trobar diferències objectivables del control postural respecte la població normal.

Ca(2+) signaling by T-type Ca(2+) channels in neurons.

Among the major families of voltage-gated Ca(2+) channels, the low-voltage-activated channels formed by the Ca(v)3 subunits, referred to as T-type Ca(2+) channels, have recently gained increased interest in terms of the intracellular Ca(2+) signals generated upon their activation. Here, we provide an overview of recent reports documenting that T-type Ca(2+) channels act as an important Ca(2+) source in a wide range of neuronal cell types. The work is focused on T-type Ca(2+) channels in neurons, but refers to non-neuronal cells in cases where exemplary functions for Ca(2+) entering through T-type Ca(2+) channels have been described. Notably, Ca(2+) influx through T-type Ca(2+) channels is the predominant Ca(2+) source in several neuronal cell types and carries out specific signaling roles. We also emphasize that Ca(2+) signaling through T-type Ca(2+) channels occurs often in select subcellular compartments, is mediated through strategically co-localized targets, and is exploited for unique physiological functions.

Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome is linked to dysregulated monocyte IL-1β production.

BACKGROUND: The exact pathogenesis of the pediatric disorder periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome is unknown. OBJECTIVES: We hypothesized that PFAPA might be due to dysregulated monocyte IL-1β production linked to genetic variants in proinflammatory genes. METHODS: Fifteen patients with PFAPA syndrome were studied during and outside a febrile episode. Hematologic profile, inflammatory markers, and cytokine levels were measured in the blood. The capacity of LPS-stimulated PBMCs and monocytes to secrete IL-1β was assessed by using ELISA, and active IL-1β secretion was visualized by means of Western blotting. Real-time quantitative PCR was performed to assess cytokine gene expression. DNA was screened for variants of the MEFV, TNFRSF1A, MVK, and NLRP3 genes in a total of 57 patients with PFAPA syndrome. RESULTS: During a febrile attack, patients with PFAPA syndrome revealed significantly increased neutrophil counts, erythrocyte sedimentation rates, and C-reactive protein, serum amyloid A, myeloid-related protein 8/14, and S100A12 levels compared with those seen outside attacks. Stimulated PBMCs secreted significantly more IL-1β during an attack (during a febrile episode, 575 ± 88 pg/mL; outside a febrile episode, 235 ± 56 pg/mL; P < .001), and this was in the mature active p17 form. IL-1β secretion was inhibited by ZYVAD, a caspase inhibitor. Similar results were found for stimulated monocytes (during a febrile episode, 743 ± 183 pg/mL; outside a febrile episode, 227 ± 92 pg/mL; P < .05). Genotyping identified variants in 15 of 57 patients, with 12 NLRP3 variants, 1 TNFRSF1A variant, 4 MEFV variants, and 1 MVK variant. CONCLUSION: Our data strongly suggest that IL-1β monocyte production is dysregulated in patients with PFAPA syndrome. Approximately 20% of them were found to have NLRP3 variants, suggesting that inflammasome-related genes might be involved in this autoinflammatory syndrome.

Breast and cervical cancer screening programme implementation in 16 countries.

OBJECTIVES: There is a continuing need to monitor and evaluate the impact of organized screening programmes on cancer incidence and mortality. We report results from a programme assessment conducted within the International Cancer Screening Network (ICSN) to understand the characteristics of cervical screening programmes within countries that have established population-based breast cancer screening programmes. METHODS: In 2007-2008, we asked 26 ICSN country representatives to complete a web-based survey that included questions on breast and cervical cancer screening programmes. We summarized information from 16 countries with both types of organized programmes. RESULTS: In 63% of these countries, the organization of the cervical cancer screening programme was similar to that of the breast cancer screening programme in the same country. There were differences in programme characteristics, including year established (1962-2003 cervical; 1986-2002 breast) and ages covered (15-70+ cervical; 40-75+ breast). Adoption of new screening technologies was evident (44% liquid-based Pap tests; 13% human papillomavirus (HPV)-triage tests cervical; 56% digital mammography breast). There was wide variation in participation rates for both programme types (<4-80% cervical; 12-88% breast), and participation rates tended to be higher for cervical (70-80%) than for breast (60-70%) cancer screening programmes. Eleven ICSN member countries had approved the HPV vaccine and five more were considering its use in their organized programmes. CONCLUSION: Overall, there were similarities and differences in the organization of breast and cervical cancer screening programmes among ICSN countries. This assessment can assist established and new screening programmes in understanding the organization and structure of cancer screening programmes.

Modulation of the gap junction protein Connexin36 in neurons in a mouse model of transient focalcerebral ischemia

Intercellular communication is achieved at specialized regions of the plasma membrane by¦gap junctions. Gap junctions are transmembrane channels allowing direct contacts between¦the cytoplasms of neighboring cells. Each cell participates with one hemichannel, or¦connexon, made of six protein subunits named connexins. Thanks to these junctions, cells¦potentially share a pool of small molecules and metabolites, such as nucleotides, amino acids¦and second messengers.¦In an ischemic (i.e. non-perfused) territory of the brain, irreversible damage progresses over¦time from the centre of the most severe flow reduction to the periphery with less disturbed¦perfusion. Functionally impaired tissue can survive and recover if sufficient reperfusion is reestablished¦within a limited time period, which depends on various factors and mechanisms¦modulating the signaling pathways leading to cell death.¦Observations were made indicating the presence of electrical coupling between neurons which¦resist better to an ischemic insult. This electrical coupling is likely to be mediated by¦Connexin36 (Cx36), a neuron specific connexin isoform. It was demonstrated in the past that¦global ischemia induces a selective upregulation of Cx36 expression in regions with neurons¦that survive the insult whereas others undergo apoptosis and die. These observations raise the¦possibility that the neuronal gap junction Cx36 might play a role in the destiny of neurons¦after cerebral ischemia.¦The aim of this work was to characterize the regulation of Connexin36 in a mouse model of¦transient focal cerebral ischemia by immunofluorescence and Western blot analysis. Our¦immunofluorescence results suggest a specific increase in Cx36 in the penumbral region of¦the ischemic hemisphere.