RESUMEN
Postoperative resynostosis and secondary craniofacial growth abnormalities are common sequelae after craniofacial surgery. It has been suggested that an overexpression of transforming growth factor-beta2 (Tgf-beta2) may be related to craniosynostosis and contribute to postoperative resynostosis. Interference with Tgf-beta2 function using neutralizing antibodies may inhibit resynostosis and improve postoperative craniofacial growth; the present study was designed to test this hypothesis. Twenty-nine New Zealand white rabbits with bilateral coronal suture synostosis were used: 1) suturectomy controls (n=9); 2) suturectomy with nonspecific, control IgG antibody (n=9); and 3) suturectomy with anti-Tgf-beta2 antibody (n=11). At 10 days of age, a 3 mm x 15-mm coronal suturectomy was performed. The sites in groups 2 and 3 were immediately filled with 0.1 cc of a slow resorbing collagen gel mixed with either IgG (100 microg/suture) or anti-Tgf-beta2 (100 microg/suture). Three-dimensional computed tomography scan reconstructions of the skulls and cephalographs were obtained at 10, 25, 42, and 84 days of age. Computed tomography scan data revealed patent suturectomy sites and significantly (P<0.05) greater intracranial volumes by 84 days of age in rabbits treated with anti-Tgf-beta2 compared with controls. Cephalometric analysis revealed significant (P<0.05) differences in craniofacial, cranial vault, and cranial base growth by 84 days of age in rabbits treated with anti-Tgf-beta2 compared with controls. These data support the initial hypothesis that interference with Tgf-beta2 function inhibited postoperative resynostosis and improved cranial vault growth in this rabbit model. Thus, this biologically based therapy may be a potential surgical adjunct in the treatment of infants with craniosynostosis.
Asunto(s)
Anticuerpos/uso terapéutico , Craneosinostosis/prevención & control , Craneosinostosis/cirugía , Factores Inmunológicos/uso terapéutico , Factor de Crecimiento Transformador beta2/antagonistas & inhibidores , Análisis de Varianza , Animales , Encéfalo/crecimiento & desarrollo , Cefalometría , Craneosinostosis/etiología , Craneotomía/efectos adversos , Cuidados Posoperatorios , Conejos , Distribución Aleatoria , Prevención Secundaria , Cráneo/crecimiento & desarrollo , Tomografía Computarizada por Rayos XRESUMEN
Two cases are reported of inappropriate implantable cardioverter-defibrillator shocks due to external alternating current leak. Electromagnetic interference (EMI) can mimic cardiac signals and cause inappropriate implantable cardioverter-defibrillator (ICD) shocks. EMI can arise from the normal functioning of electrical appliances or from alternating current leak. The two cases had inappropriate ICD shocks due to alternating current leak from a power drill in one and a washing machine in the other. The need for detailed advice on handling electrical equipment is emphasized.
Asunto(s)
Desfibriladores Implantables/efectos adversos , Electricidad/efectos adversos , Taquicardia Ventricular/terapia , Adulto , Electrocardiografía , Falla de Equipo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Vascular endothelial growth factor (VEGF) plays a critical role during normal embryonic angiogenesis and also in the pathological angiogenesis that occurs in a number of diseases, including cancer. Initial attempts to block VEGF by using a humanized monoclonal antibody are beginning to show promise in human cancer patients, underscoring the importance of optimizing VEGF blockade. Previous studies have found that one of the most effective ways to block the VEGF-signaling pathway is to prevent VEGF from binding to its normal receptors by administering decoy-soluble receptors. The highest-affinity VEGF blocker described to date is a soluble decoy receptor created by fusing the first three Ig domains of VEGF receptor 1 to an Ig constant region; however, this fusion protein has very poor in vivo pharmacokinetic properties. By determining the requirements to maintain high affinity while extending in vivo half life, we were able to engineer a very potent high-affinity VEGF blocker that has markedly enhanced pharmacokinetic properties. This VEGF-Trap effectively suppresses tumor growth and vascularization in vivo, resulting in stunted and almost completely avascular tumors. VEGF-Trap-mediated blockade may be superior to that achieved by other agents, such as monoclonal antibodies targeted against the VEGF receptor.