A CWR technique can provide improved intraoperative exposure of the middle ear and mastoid without creating a mastoid bowl and reduces the incidence of recurrent disease. A single procedure is used for all patients with acquired cholesteatoma, including children.
We have shown previously that BDNF, neurotrophin-3 (NT-3), chlorphenylthio-cAMP (cpt-cAMP) (a permeant cAMP analog), and membrane depolarization promote spiral ganglion neuron (SGN) survival in vitro in an additive manner, depolarization having the greatest efficacy. Expression of both BDNF and of NT-3 is detectable in cultured SGNs after plating in either depolarizing or nondepolarizing medium. These neurotrophins promote survival by an autocrine mechanism; TrkB-IgG or TrkC-IgG, which block neurotrophin binding to, respectively, TrkB and TrkC, partially inhibit the trophic effect of depolarization. The mitogen-activated protein kinase kinase inhibitor PD98059 and the phosphatidylinositol-3-OH kinase inhibitor LY294002 both abolish trophic support by neurotrophins but only partially inhibit support by depolarization. Inhibition by these compounds is not additive with inhibition by Trk-IgGs. The cAMP antagonist Rp-adenosine-3Ј,5Ј-cyclic-phosphorothioate (Rp-cAMPS) abolishes survival attributable to cptcAMP but has no effect on that attributable to neurotrophins, nor do inhibitors of neurotrophin-dependent survival affect survival attributable to cpt-cAMP. However, Rp-cAMPS does partially inhibit depolarization-dependent survival, an inhibition that is additive with that by Trk-IgGs, PD98059, or LY294002. Moreover, Rp-cAMPS prevents depolarization-dependent survival of PC12 cells maintained in subthreshold levels of NGF. Inhibition of Ca 2ϩ /calmodulin-dependent protein kinases (CaMKs) with KN-62 reduces SGN survival independently of Rp-cAMPS, Trk-IgGs, and LY294002 and additively with them. Combined inhibition of Trk, cAMP, and CaMK signaling prevents depolarization-dependent survival. Thus, survival of SGNs under depolarizing conditions involves additivity among a depolarization-independent autocrine pathway, a cAMPdependent pathway, and a CaMK-dependent pathway.
Patients with spontaneous CSF leak are more likely to be obese, have the diagnosis of OSA, and show thinning of their entire calvarium that is independent of BMI. These data suggest an additional obesity-associated intracranial process contributes to skull thinning.
Hypothesis-Elevated levels of hsa-microRNA-21 (miR-21) in vestibular schwannomas (VSs) may contribute to tumor growth by down-regulating the tumor suppressor gene phosphatase and tensin homolog (PTEN) and consequent hyperactivation of protein kinase B (AKT), a key signaling protein in the cellular pathways that lead to tumor growth.Background-VSs are benign tumors that arise from the vestibular nerve. Left untreated, VSs can result in hearing loss, tinnitus, vestibular dysfunction, trigeminal nerve dysfunction and can even become life threatening. Despite efforts to characterize the VS transcriptome, the molecular pathways that lead to tumorigenesis are not completely understood. MicroRNAs are small RNA molecules that regulate gene expression post-transcriptionally by blocking the production of specific target proteins.
Objective-To determine the ability of ErbB inhibitors to reduce the growth of vestibular schwannoma (VS) xenografts.Methods-VS xenografts were established in the interscapular fat pad in nude mice for 4 weeks. Initially, a small cohort of animals was treated with the ErbB2 inhibitor, trastuzumab, or saline for 2 weeks. Animals also received BrdU injections to label proliferating cells. In a longer-term experiment, animals were randomized to receive trastuzumab, erlotinib (an ErbB kinase inhibitor), or placebo for 12 weeks. Tumor growth was monitored by magnetic resonance imaging (MRI) over the treatment period. Cell death was analyzed by terminal dUTP nick end labeling (TUNEL).Results-Tumors could be distinguished with T2 weighted MRI sequences. Trastuzumab significantly reduced the proliferation of VS cells compared to control (p<0.01) as determined by BrdU uptake. Control tumors demonstrated slight growth over the 12 week treatment period. Both trastuzumab and erlotinib significantly reduced the growth of VS xenografts (p<0.05). Erlotinib, but not trastuzumab, resulted in a significant increase in the percent of TUNEL-positive VS cells (p<0.01).Conclusions-In this preliminary study, the ErbB inhibitors trastuzumab and erlotinib decreased growth of VS xenografts in nude mice raising the possibility of using ErbB inhibitors in the management of patients with schwannomas, particularly those with neurofibromatosis type 2.
Purpose of review Advancements in cochlear implant surgical approaches and electrode designs have enabled preservation of residual acoustic hearing. Preservation of low-frequency hearing allows cochlear implant users to benefit from electroacoustic stimulation, which improves performance in complex listening situations, such as music appreciation and speech understanding in noise. Despite the relative high rates of success of hearing preservation, postoperative acoustic hearing outcomes remain unpredictable. Recent findings Thin, flexible, lateral wall arrays are preferred for hearing preservation. Both shortened and thin, lateral wall arrays have shown success with hearing preservation and the optimal implant choice is an issue of ongoing investigation. Electrocochleography can monitor cochlear function during and after insertion of the electrode array. The pathophysiology of hearing loss acutely after cochlear implant may differ from that involved in delayed hearing loss following cochlear implant. Emerging innovations may reduce cochlear trauma and improve hearing preservation. Summary Hearing preservation is possible using soft surgical techniques and electrode arrays designed to minimize cochlear trauma; however, a subset of patients suffer from partial to total loss of acoustic hearing months to years following surgery despite evidence of residual apical hair cell function. Early investigations in robotic-assisted insertion and dexamethasone-eluting implants show promise.
Famciclovir administered preoperatively and after craniotomies resulted in a smaller percentage of patients developing delayed facial weakness. We are continuing the routine use of famciclovir in perioperative acoustic tumor management and recommend that others do so.
Objectives: To compare intraoperative intracochlear electrocochleography (ECochG) with hearing preservation outcomes in cochlear implant (CI) subjects. Design: Intraoperative electrocochleography was performed in adult CI subjects who were recipients of Advanced Bionics' Bionics LLC precurved HiFocus MidScala or straight HiFocus SlimJ electrode arrays. ECochG responses were recorded from the most apical electrode contact during insertion. No changes to the insertions were made due to ECochG monitoring. No information about insertion resistance was collected. ECochG drops were estimated as the change in amplitude from peak (defined as maximum amplitude response) to drop (largest drop) point after the peak during insertion was measured following the peak response. Audiometric thresholds from each subject were obtained before and approximately 1 month after CI surgery. The change in pure tone average for frequencies between 125 Hz and 500 Hz was measured after surgery. No postoperative CT scans were collected as part of this study. Results: A total of 68 subjects from five surgical centers participated in the study. The study sample included 30 MidScala and 38 SlimJ electrodes implanted by approximately 20 surgeons who contributed to the study. Although a wide range of results were observed, there was a moderate positive correlation (Pearson Correlation coefficient, r ¼ 0.56, p < 0.01) between the size of the ECochG drop and the magnitude of pure tone average change. This trend was present for both the MidScala and SlimJ arrays. The SlimJ and MidScala arrays produced significantly different hearing loss after surgery. Conclusion: Large ECochG amplitude drops observed during electrode insertion indicated poorer hearing preservation. Although the outcomes were variable, this information may be helpful to guide surgical decision-making when contemplating full electrode insertion and the likelihood of hearing preservation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.