Tumor necrosis factor-alpha (TNF) is upregulated after nerve injury, causes pain on injection, and its blockade reduces pain behavior resulting from nerve injury; thus it is strongly implicated in neuropathic pain. We investigated responses of intact and nerve-injured dorsal root ganglia (DRG) neurons to locally applied TNF using parallel in vivo and in vitro paradigms. In vivo, TNF (0.1-10 pg/ml) or vehicle was injected into L5 DRG in naive rats and in rats that had received L5 and L6 spinal nerve ligation (SNL) immediately before injection. In naive rats, TNF, but not vehicle, elicited long-lasting allodynia. In SNL rats, subthreshold doses of TNF synergized with nerve injury to elicit faster onset of allodynia and spontaneous pain behavior. Tactile allodynia was present in both injured and adjacent uninjured (L4) dermatomes. Preemptive treatment with the TNF antagonist etanercept reduced SNL-induced allodynia by almost 50%. In vitro, the electrophysiological responses of naive, SNL-injured, or adjacent uninjured DRG to TNF (0.1-1000 pg/ml) were assessed by single-fiber recordings of teased dorsal root microfilaments. In vitro perfusion of TNF (100-1000 pg/ml) to naive DRG evoked short-lasting neuronal discharges. In injured DRG, TNF, at much lower concentrations, elicited earlier onset, markedly higher, and longer-lasting discharges. TNF concentrations that were subthreshold in naive DRG also elicited high-frequency discharges when applied to uninjured, adjacent DRG. We conclude that injured and adjacent uninjured DRG neurons are sensitized to TNF after SNL. Sensitization to endogenous TNF may be essential for the development and maintenance of neuropathic pain.
To investigate posterior external ear canal wall reconstruction with a composite cartilage titanium mesh graft in canal wall down tympanoplasty and revision surgery for open mastoids.Retrospective case review.Tertiary referral centre.As a preliminary study, 15 selected patients underwent reconstruction of a posterior ear canal wall defect with titanium mesh. Large defects of the posterior external auditory canal wall, resulting from canal wall down tympanoplasty or present in revision surgery, were eliminated by reconstruction using a titanium mesh. The mesh was covered with conchal cartilage and attached to the cortical mastoid bone using 3-mm titanium screws.All patients maintained a normal contour of the external ear canal, without depression, extrusion or infection. There were no failures, based on short-term post-operative controls. However, two procedures had to be revised due to incomplete coverage of the titanium mesh.This study shows that reconstruction of the posterior ear canal wall with a composite cartilage titanium mesh is a valuable method for preserving the morphology of the external auditory canal in selected cases. Problems occurring in canal wall down tympanomastoidectomy and radical cavities may therefore be avoided. However, long-term results have yet to be evaluated.
Tumor necrosis factor-α (TNF) is upregulated after nerve injury, causes pain on injection, and its blockade reduces pain behavior resulting from nerve injury; thus it is strongly implicated in neuropathic pain. We investigated responses of intact and nerve-injured dorsal root ganglia (DRG) neurons to locally applied TNF using parallel in vivo and in vitro paradigms. In vivo , TNF (0.1–10 pg/ml) or vehicle was injected into L5 DRG in naive rats and in rats that had received L5 and L6 spinal nerve ligation (SNL) immediately before injection. In naive rats, TNF, but not vehicle, elicited long-lasting allodynia. In SNL rats, subthreshold doses of TNF synergized with nerve injury to elicit faster onset of allodynia and spontaneous pain behavior. Tactile allodynia was present in both injured and adjacent uninjured (L4) dermatomes. Preemptive treatment with the TNF antagonist etanercept reduced SNL-induced allodynia by almost 50%. In vitro , the electrophysiological responses of naive, SNL-injured, or adjacent uninjured DRG to TNF (0.1–1000 pg/ml) were assessed by single-fiber recordings of teased dorsal root microfilaments. In vitro perfusion of TNF (100–1000 pg/ml) to naive DRG evoked short-lasting neuronal discharges. In injured DRG, TNF, at much lower concentrations, elicited earlier onset, markedly higher, and longer-lasting discharges. TNF concentrations that were subthreshold in naive DRG also elicited high-frequency discharges when applied to uninjured, adjacent DRG. We conclude that injured and adjacent uninjured DRG neurons are sensitized to TNF after SNL. Sensitization to endogenous TNF may be essential for the development and maintenance of neuropathic pain.
Low-pressure chemical vapor deposition of tungsten silicide has been done and the properties of the deposited films have been studied to determine the process compatibility and suitability to form gate electrodes and interconnections in MOS VLSI applications. The silicide was deposited on single-crystal silicon and on oxidized silicon with and without a coating of polycrystalline silicon film. Auger analysis of the As-deposited films showed absence of any contaminants in it. X-ray diffraction and transmission electron microscopy showed that As-deposited films were microcrystalline with grains smaller than 30 Å and upon annealing became polycrystalline WSi 2 with hexagonal structure at 500°C and tetragonal structure at or above 600°C with a corresponding decrease in resistivity from 600-900 µΩ . cm to 35-60 µΩ . cm depending upon anneal temperature and time. No appreciable change in the thickness of the silicide was found during the high-temperature anneals. Silicon-rich silicide films remained stable, smooth, and free of cracks through high-temperature anneals and oxidations, and their adherence to the wafer remained excellent. On the other hand, metal-rich films had overall inferior properties. Thermal oxidation of WSi 2 on polysilicon in dry oxygen in the temperature range of 900 to 1100°C was found to be similar to that of silicon except the linear regime of oxidation was extremely rapid and the entire process could be modeled by a parabolic equation X^{2) = Bt with an activation energy of 1.7 eV. MOS capacitors were fabricated with silicide and polycide gate electrodes. Polysilicon thickness variation from 0 to 5000 Å had no adverse effect on the electrical characteristics or mechanical integrity of the devices. In all cases, low values of N f (1 × 10 10 -7 × 10 10 cm -2 ) and N it (< 10 10 cm -2 . eV -1 ) and high gate oxide dielectric strength ( \sime 8 MV/cm) were obtained.
Tumor necrosis factor-alpha (TNF) appears as a key player at both central and peripheral terminals in early degenerative pathology and pain behavior after peripheral nerve injury. Recent studies suggest that TNF may be axonally transported and thereby contribute to these central and peripheral actions. To characterize this transport, we used a double ligation (DL) procedure that distinguishes between anterograde and retrograde flow to visualize the axonal transport of endogenous TNF compared with the neurotrophin nerve growth factor (NGF) and to the neuropeptide calcitonin gene-related peptide (CGRP). In the intact nerve, TNF and CGRP immunoreactivity predominantly accumulated proximal to the DL (anterograde transport), whereas NGF displayed exclusive retrograde transport. At 20 hr after chronic constrictive injury (CCI), the anterograde transport of TNF and CGRP to the nerve injury site was dramatically increased. The results were corroborated by the analysis of axonal transport of exogenously applied 125I-TNF and 125I-NGF. After intraneural injection, 125I-TNF accumulated proximally to a DL, suggesting anterograde transport. In the unligated nerve, 125I-TNF was specifically transported anterogradely to the innervated muscle but not to skin. After CCI, 125I-TNF accumulated proximally to the peripheral nerve injury site, and endogenous TNF was exclusively increased in medium-sized and large dorsal root ganglion (DRG) neurons, suggesting that DRG neurons are a major contributing source of increased TNF traffic in the injured sciatic nerve. Our results suggest that anterograde transport of TNF plays a major role in the early neuronal response to peripheral nerve injury at sites distal to the cell body.
Objective--Neurotrophins and extracellular matrix (ECM) molecules are involved in neurite guidance during the development of spiral ganglion (SG) neurons. Several intracellular signaling molecules can be activated by ECMs and neurotrophins via their cognate receptors. In other systems these include the Rho small GTPases, which influence reorganization of the actin cytoskeleton that is required for axon growth. The aim of this study was to determine whether neurotrophin-3 (NT-3)-mediated SG neurite outgrowth on laminin-1 (LN) is dependent on the activation of the small GTPases Rho/Rac/Cdc42. Material and methods--SG explants from postnatal Day 4 rats were cultured on LN with and without NT-3 and increasing concentrations of Clostridium difficile Toxin B, an inhibitor of Rho GTPases. After fixation and immunocytochemical labeling, neurite growth was evaluated. Results--Treatment with C. difficile Toxin B without NT-3 lead to a dose-dependent decrease in the length and number of processes on LN. In contrast, C. difficile Toxin B had no significant effect on NT-3-mediated stimulation of neurite growth on LN, in terms of either number or length. Conclusion--The results suggest that the Rho GTPases (Rho, Rac and Cdc42) are not involved in the pathways linking NT-3 signals to neurite outgrowth, but appear to be involved in LN signaling in these neurons. However, NT-3 can override or bypass LN signaling to promote neurite extension.
Surgery is the most common treatment for angiofibromas, but the approach is still a major point of discussion. Five cases of angiofibroma with typical localisation were treated surgically by an endonasal approach at the Fulda Academic Teaching Hospital from 1994 to 1997. This article presents an analysis of the clinical findings, computer tomography and magnetic resonance imaging, preoperative embolization, operative technique and complications. Endoscopic and radiologic follow-up ranging from 5 to 39 months excluded any residual tumour or recurrence. The endonasal microendoscopic approach with adequate preoperative embolization should be considered as an useful technique for removing tumours with considerable size without using an external incision.
