Multiplicity of cerebrospinal fluid functions: New challenges in health and disease

This review integrates eight aspects of cerebrospinal fluid (CSF) circulatory dynamics: formation rate, pressure, flow, volume, turnover rate, composition, recycling and reabsorption. Novel ways to modulate CSF formation emanate from recent analyses of choroid plexus transcription factors (E2F5), ion transporters (NaHCO3 cotransport), transport enzymes (isoforms of carbonic anhydrase), aquaporin 1 regulation, and plasticity of receptors for fluid-regulating neuropeptides. A greater appreciation of CSF pressure (CSFP) is being generated by fresh insights on peptidergic regulatory servomechanisms, the role of dysfunctional ependyma and circumventricular organs in causing congenital hydrocephalus, and the clinical use of algorithms to delineate CSFP waveforms for diagnostic and prognostic utility. Increasing attention focuses on CSF flow: how it impacts cerebral metabolism and hemodynamics, neural stem cell progression in the subventricular zone, and catabolite/peptide clearance from the CNS. The pathophysiological significance of changes in CSF volume is assessed from the respective viewpoints of hemodynamics (choroid plexus blood flow and pulsatility), hydrodynamics (choroidal hypo- and hypersecretion) and neuroendocrine factors (i.e., coordinated regulation by atrial natriuretic peptide, arginine vasopressin and basic fibroblast growth factor). In aging, normal pressure hydrocephalus and Alzheimer's disease, the expanding CSF space reduces the CSF turnover rate, thus compromising the CSF sink action to clear harmful metabolites (e.g., amyloid) from the CNS. Dwindling CSF dynamics greatly harms the interstitial environment of neurons. Accordingly the altered CSF composition in neurodegenerative diseases and senescence, because of adverse effects on neural processes and cognition, needs more effective clinical management. CSF recycling between subarachnoid space, brain and ventricles promotes interstitial fluid (ISF) convection with both trophic and excretory benefits. Finally, CSF reabsorption via multiple pathways (olfactory and spinal arachnoidal bulk flow) is likely complemented by fluid clearance across capillary walls (aquaporin 4) and arachnoid villi when CSFP and fluid retention are markedly elevated. A model is presented that links CSF and ISF homeostasis to coordinated fluxes of water and solutes at both the blood-CSF and blood-brain transport interfaces

Present and future evolution of advanced breast cancer therapy

Although the introduction of novel therapies and drug combinations has improved the prognosis of metastatic breast cancer, the disease remains incurable. Increased knowledge of the biology and the molecular alterations in breast cancer has facilitated the design of targeted therapies. These agents include receptor and nonreceptor tyrosine kinase inhibitors (epidermal growth factor receptor family), intracellular signaling pathways (phosphatidylinositol-3-kinase, AKT, mammalian target of rapamycin) angiogenesis inhibitors and agents that interfere with DNA repair (poly(ADP-ribose) polymerase inhibitors). In the present review, we present the most promising studies of these new targeted therapies and novel combinations of targeted therapies with cytotoxic agents

Resultados de una encuesta sobre tratamiento de la cifosis torácica causada por enfermedad de Scheuermann Resultados de uma pesquisa sobre o tratamento da cifose torácica de Scheuermann Results of a survey on the treatment of thoracic Scheuermann´s kyphosis

OBJETIVO: Conocer que parámetros se deben considerar para encarar el tratamiento de la cifosis torácica causada por la enfermedad de Scheuermann. MÉTODO: Se realizó una recolección de informaciones consistente en aplicar un cuestionario a 25 informantes calificados, colegas de diferentes países de Íbero/Latinoamérica miembros de SILACO (Sociedad Íbero/Latinoamericana de Columna) y se analizaron los resultados de las mismas. RESULTADOS: Como tratamiento ortopédico, la mayoría se inclinó por el uso del corsé de Milwaukee, indicado en pacientes prepúberes y pospúberes con curvas mayores de 60º y en curvas de menos de 60º si tienen dolor. El tiempo de uso: 22 hrs por día, su mantenimiento hasta llegar a Risser 4 o 5. Se observó una tasa de abandono de 48% al plan terapéutico. En lo referente a tratamiento quirúrgico, las indicaciones surgen: por localización de la deformidad, el valor angular, dolor, edad y estética. La extensión del área a fusionar fue determinada con los espinogramas y radiografías dinámicas. Se eligió la vía posterior como vía de abordaje con barras y tornillos, y en algunos casos la combinación con ganchos. Se evaluaron los resultados del tratamiento quirúrgico (de acuerdo a la opinión del médico), que fueron catalogados como buenos en un 64%. CONCLUSIONES: Se realizó una encuesta de opinión sobre el tratamiento de la cifosis torácica causada por enfermedad de Scheuermann .y se analizaron 25 formularios de respuestas de calificados cirujanos de columna, de diferentes países de Ibero/Latinoamérica miembros de SILACO. La encuesta ha permitido establecer normas de conducta terapéuticas (ortopédicas y quirúrgicas) para el tratamiento de esta afección.<br>OBJETIVO: Obter os parâmetros a serem considerados para realizar o tratamento da cifose torácica de Scheuermann. MÉTODOS: Os dados foram obtidos por meio de um questionário que foi respondido por 25 membros da SILACO (Sociedad Ibero-Latino-americana de Columna) e análise dos resultados das respostas. RESULTADOS: Como tratamento ortopédico, a maioria optou pelo uso do colete de Milwaukee indicado para pacientes pré-púberes e pós-púberes com curvas maiores que 60° e curvas de menos de 60° acompanhadas de dor. O tempo de uso diário do colete foi de 22 horas até atingir Risser 4 ou 5. A taxa de abandono do plano terapêutico foi de 48%. Em relação ao tratamento cirúrgico, a maioria afirmou que as indicações estão relacionadas com localização da deformidade, valor angular, dor, idade e a estética. A extensão da área da artrodese foi determinada por meio de radiografias totais de coluna e dinâmicas. A abordagem posterior foi escolhida como a via de acesso preferida, utilizando-se hastes, parafusos e associação com ganchos. CONCLUSÃO: Realizamos uma pesquisa sobre o tratamento da cifose torácica decorrente de doença Scheuermann. Analisamos 25 formulários de resposta de cirurgiões de coluna qualificados de diferentes países membros da SILACO. A pesquisa permitiu estabelecer normas de conduta terapêutica (ortopédicas e cirúrgicas) para tratamento dessa afecção.<br>OBJECTIVE: To determine which parameters should be considered to address the treatment of thoracic Scheuermann kyphosis. METHOD: A survey information with a questionnaire applied to 25 informants, colleagues from different countries of Ibero-Latin American members of SILACO (Sociedad Ibero-Latinoamericana de Columna) and to analyze the results. RESULTS: Regarding to the orthopedic treatment the majority tended towards the use of Milwaukee brace for pre-pubertal and post-pubertal patients with curves greater than 60º and in curves of less than 60º if they had pain. Time of use: Twenty two hours per day until reaching Risser of 4 or 5. The rejection rate of the therapeutic plan was 48%. Regarding surgical treatment, the majority established that the indications are related to the location of the deformity, the angular value, pain, age and aesthetics. The extension of the area to be fused was determined by the total column and dynamic X-rays. Posterior approach was chosen to access; rod and screws, and in some cases the combination with hooks. CONCLUSION: We conducted a survey about the treatment of thoracic kyphosis due to Scheuermann disease and analyzed 25 response forms of qualified spine surgeons from different countries that are SILACO members. The survey has allowed to establish standards of management (orthopedic and surgical) for the treatment of this condition

Biomechanical evaluation of a new fixation device for the thoracic spine

The technology used in surgery for spinal deformity has progressed rapidly in recent years. Commonly used fixation techniques may include monofilament wires, sublaminar wires and cables, and pedicle screws. Unfortunately, neurological complications can occur with all of these, compromising the patients’ health and quality of life. Recently, an alternative fixation technique using a metal clamp and polyester belt was developed to replace hooks and sublaminar wiring in scoliosis surgery. The goal of this study was to compare the pull-out strength of this new construct with sublaminar wiring, laminar hooks and pedicle screws. Forty thoracic vertebrae from five fresh frozen human thoracic spines (T5–12) were divided into five groups (8 per group), such that BMD values, pedicle diameter, and vertebral levels were equally distributed. They were then potted in polymethylmethacrylate and anchored with metal screws and polyethylene bands. One of five fixation methods was applied to the right side of the vertebra in each group: Pedicle screw, sublaminar belt with clamp, figure-8 belt with clamp, sublaminar wire, or laminar hook. Pull-out strength was then assessed using a custom jig in a servohydraulic tester. The mean failure load of the pedicle screw group was significantly larger than that of the figure-8 clamp (P = 0.001), sublaminar belt (0.0172), and sublaminar wire groups (P = 0.04) with no significant difference in pull-out strength between the latter three constructs. The most common mode of failure was the fracture of the pedicle. BMD was significantly correlated with failure load only in the figure-8 clamp and pedicle screw constructs. Only the pedicle screw had a statistically significant higher failure load than the sublaminar clamp. The sublaminar method of applying the belt and clamp device was superior to the figure-8 method. The sublaminar belt and clamp construct compared favorably to the traditional methods of sublaminar wires and laminar hooks, and should be considered as an alternative fixation device in the thoracic spine