Continuous facial nerve monitoring during pleomorphic adenoma recurrence surgery

OBJECTIVES: Surgery of recurrent pleomorphic adenoma (RPA) is known to lead to a high facial nerve complication rate. The efficacy of the continuous facial nerve monitoring (CFNM) technique remains to be proven in RPA surgery. The goal was thus to evaluate facial nerve palsy rates and the recovery period after parotidectomy for RPA using CFNM by way of continuous electromyography and to compare these rates and the operation time with those of patients who had undergone surgery without facial nerve monitoring. DESIGN: Cohort study. PATIENTS: Forty-seven patients were referred for RPA (1981-2003). Among them, 32 (18 unmonitored and 14 monitored) patients displayed no preoperative facial palsy, and histologic analyses revealed evidence of recurrence. The operation time and the extent and duration of postoperative facial nerve palsy were examined in both groups (monitored vs. unmonitored). Both groups had a similar clinical appearance distribution. RESULTS: Facial nerve paralysis was estimated using the House-Brackmann grading scale. CFNM reduced the intensity of facial nerve paralysis independently of the kind of surgery performed. The complete deficit rates were 0% for the monitored group and 5.6% for the unmonitored group. Postoperative facial nerve paralysis was significantly lower (P = .01) in the monitored group than in the unmonitored group. CFNM improved the duration of facial paralysis (P = .001) in the monitored group. The operation time was significantly lower in the monitored group than in the unmonitored group (P = .001). CONCLUSIONS: Routine use of CFNM during RPA surgery improves the surgical outcome. The facial nerve deficit can be reduced, and the recovery of facial nerve function is faster.     

Differential induction of apoptosis by tumor necrosis factor-related apoptosis-inducing ligand in human ovarian carcinoma cells

OBJECTIVES: In this study, we examine the sensitivity of a panel of ovarian carcinoma cells, which includes four primary ovarian cancer cell samples, and four normal ovarian epithelium samples to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We also examine the intracellular regulation of TRAIL-mediated apoptosis. METHODS: The sensitivity to TRAIL was determined by short-term survival assays on seven ovarian carcinoma cell lines, four primary samples of ovarian cancer, and four normal ovarian epithelium samples. We assessed the activation of the apoptotic pathway in TRAIL-resistant and -sensitive tumor cells. The expression of TRAIL receptors was determined by flow cytometry. The protein expression of FADD, XIAP, caspase-8, caspase-3, BAX, and c-FLIP were determined by immunoblot analyses. RESULTS: We show that ovarian cancer cells display variable sensitivity to TRAIL-induced apoptosis although most cell lines have similar sensitivity to cisplatin. Normal ovarian epithelium samples were mostly sensitive to TRAIL. In sensitive cells, TRAIL induced caspase-8-dependent apoptosis, which subsequently led to activation of caspase-3. Both sensitive and resistant cells expressed caspase-8, caspase-3, FADD, XIAP, and c-FLIP at similar levels. A significant enhancement in cell death was observed in TRAIL-resistant cells when c-FLIP(L) levels were downregulated by RNA interference. CONCLUSIONS: These data suggest that sensitivity to TRAIL and chemotherapy does not necessarily correlate in human ovarian cancer cells. Cancerous cells isolated from patients with ovarian cancer show variable sensitivity to TRAIL but most normal ovarian epithelial cells are sensitive. In human ovarian cancer cells, c-FLIP(L) may participate to the regulation of the TRAIL signaling cascade.     

Large-displacement 3D structural analysis of an aortic valve model with nonlinear material properties

Grafts used in aortic valve-sparing procedures should ideally not only reproduce the geometry of the natural aortic root but also its material properties. Indeed, a number of studies using the finite element method have shown the importance of the natural sinus shape of the root in the functioning of the normal aortic valve, and the relative increase in stresses due to the replacement of the valve by a stiffer synthetic graft. Because of the wide range in experimentally measured values of aortic wall and leaflet material properties, studies by different research groups have incorporated very different material properties in their models. The aim of the present study was to investigate the influence of material properties on aortic wall displacements, and to determine which material properties would most closely match reported experimental data. Two geometrically accurate 3D models corresponding to the closed and open valve configurations were created in Pro/Engineer CAD software. Loads corresponding to systolic and diastolic pressures were specified and large-displacement structural analyses were carried out using the ANSYS package. Results have indicated that the closest match to experiments using isotropic material properties occurred for a Young's modulus of about 2000 KPa. Nonlinear models based on experimental stress-strain curves have shown similar displacements, but altered strain distribution patterns and significantly lower stresses. These results suggest that an accurate comparison of potential new graft models would have to be made with natural aortic valve models incorporating nonlinear material behavior.     

Polyelectrolyte Nanoparticles Mediate Vascular Gene Delivery

PURPOSE: The purpose is to develop a non-viral gene delivery system that meets the requirements of colloidal stability of DNA complexes expressed in terms of no particle aggregation under physiologic conditions. The system should be used to transfect cardiovascular tissues. METHODS: We used a strategy based on the formation of polyelectrolyte nanoparticles by deposition of alternatively charged polyelectrolytes onto a DNA core. Polyelectrolytes were transfer RNA as well as the synthetic polyanion, polyvinyl sulfate (PVS), and the polycation polyethylenimine (PEI). The PEI/DNA complex formed the DNA core. RESULTS: We observed that the DNA is condensed by polycations and further packaged by association with a polyanion. These nanoparticles exhibited negative surface charge and low aggregation tendency. In vivo rat carotid artery experiments revealed high transfection efficiency, not only with the reporter gene but also with the gene encoding human urokinase plasminogen activator (Hu-uPA). Hu-uPA is one of the proteins involved in the recovery of the blood vessels after balloon catheter injury and therefore clinically relevant. CONCLUSIONS: A strategy for in vivo gene transfer is proposed that uses the incorporation of polyanions as RNA or PVS into PEI/DNA complexes in order to overcome colloidal instability and to generate a negative surface charge. The particles proved to be transfectionally active in vascular gene transfer.     

Gene therapy strategies for X-linked adrenoleukodystrophy

X-linked adrenoleukodystrophy (ALD) is the most frequently seen genetic disorder involving the myelin of the central nervous system. The cerebral form affects mainly boys between five to 12 years, leading to vegetative state or death within two to four years. The adult form affects the spinal cord, leading to severe paraplegia often complicated by cerebral demyelination. The ALD gene encodes an ATP-binding cassette transporter involved in the transport of very long chain fatty acids into peroxysomes. Specific subpopulations of oligodendrocytes and microglia are particularly affected by the ALD gene mutation and thus should be the target cells of gene therapy approaches. Two different and potentially complementary therapeutic strategies are currently evaluated. The first approach aims at replacing the endogenous brain microglia from patients by autotransplantation of genetically corrected hematopoietic stem cells using a lentiviral vector. The second approach aims at targeting directly the ALD gene into brain glial cells using stereotactic injections of viral vectors.     

Chemokine-induced cell death in CCR5-expressing neuroblastoma cells

CCR5 is expressed in neurons but its function in this cellular context is hitherto poorly understood. We have generated CCR5-expressing SH-SY5Y neuroblastoma cells. CCR5 ligands induced cell death in these cells, but not in control neuroblastoma cells or in CCR5-expressing fibroblasts. CCR5-dependent killing of neuroblastoma cells occurred through apoptosis, since it was accompanied by caspase-3 activation and could be prevented by a caspase-3 inhibitor. Finally, cell killing by activated microglia was more rapid and extensive in CCR5-expressing neuroblastoma cells than in control cells. In summary, CCR5 may act as a death receptor in cells of neuronal lineage and therefore be involved in inflammatory neurodegeneration.