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1.
Acta Neurochir (Wien) ; 164(3): 669-677, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34642820

RESUMEN

BACKGROUND: Translabyrinthine approaches (TLAs) for resection of skull base neoplasms are complex with variable reconstruction techniques. Fat grafts in conjunction with hydroxyapatite bone cement techniques have seldom been described in terms of possible superiority to other skull base reconstruction techniques. We sought to determine the impact of this skull base reconstruction technique on clinical outcomes and patient's satisfaction. METHOD: We performed a retrospective analysis of all patients who underwent translabyrinthine approaches for resection of CPA lesions over a 5-year period. Both post-op objective and subjective markers of reconstruction, as well as postoperative complications, were collected and analyzed. RESULTS: Sixty-nine patients were included, 34 underwent reconstruction with hydroxyapatite and fat (rHAC) and 35 with fat alone (rF). rHAC was associated with fewer cranial wound superficial infection/dehiscence (0% vs 14.3%; p = 0.029) and shorter length of stay (mean ± standard deviation) (6.9 ± 7.4 vs 4.4 ± 3.7 days, p = 0.008). Postoperative subjective characterization of rHAC demonstrated improved satisfaction scores (1.38 ± 0.5 vs 1.83 ± 1; p = 0.049) and fewer reports of post-operative irregularities (11.5% vs 37.5%; p = 0.017). CONCLUSION: The use of hydroxyapatite for cranial reconstruction after translabyrinthine approaches has improved patient satisfaction and decreased cranial defects in our small series. Postoperative complications are consistent with other described methods, but with shorter hospital stay, decreased risk of superficial wound dehiscence/infection, and a perceived superiority in preventing percutaneous post-op CSF leaks.


Asunto(s)
Procedimientos de Cirugía Plástica , Calidad de Vida , Durapatita/uso terapéutico , Estética , Humanos , Hidroxiapatitas , Satisfacción Personal , Complicaciones Posoperatorias/etiología , Procedimientos de Cirugía Plástica/métodos , Estudios Retrospectivos , Base del Cráneo/cirugía
2.
Am J Hum Genet ; 103(5): 679-690, 2018 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-30401457

RESUMEN

Non-secretor status due to homozygosity for the common FUT2 variant c.461G>A (p.Trp154∗) is associated with either risk for autoimmune diseases or protection against viral diarrhea and HIV. We determined the role of FUT2 in otitis media susceptibility by obtaining DNA samples from 609 multi-ethnic families and simplex case subjects with otitis media. Exome and Sanger sequencing, linkage analysis, and Fisher exact and transmission disequilibrium tests (TDT) were performed. The common FUT2 c.604C>T (p.Arg202∗) variant co-segregates with otitis media in a Filipino pedigree (LOD = 4.0). Additionally, a rare variant, c.412C>T (p.Arg138Cys), is associated with recurrent/chronic otitis media in European-American children (p = 1.2 × 10-5) and US trios (TDT p = 0.01). The c.461G>A (p.Trp154∗) variant was also over-transmitted in US trios (TDT p = 0.01) and was associated with shifts in middle ear microbiota composition (PERMANOVA p < 10-7) and increased biodiversity. When all missense and nonsense variants identified in multi-ethnic US trios with CADD > 20 were combined, FUT2 variants were over-transmitted in trios (TDT p = 0.001). Fut2 is transiently upregulated in mouse middle ear after inoculation with non-typeable Haemophilus influenzae. Four FUT2 variants-namely p.Ala104Val, p.Arg138Cys, p.Trp154∗, and p.Arg202∗-reduced A antigen in mutant-transfected COS-7 cells, while the nonsense variants also reduced FUT2 protein levels. Common and rare FUT2 variants confer susceptibility to otitis media, likely by modifying the middle ear microbiome through regulation of A antigen levels in epithelial cells. Our families demonstrate marked intra-familial genetic heterogeneity, suggesting that multiple combinations of common and rare variants plus environmental factors influence the individual otitis media phenotype as a complex trait.


Asunto(s)
Fucosiltransferasas/genética , Variación Genética/genética , Otitis Media/genética , Animales , Células COS , Línea Celular , Chlorocebus aethiops , Oído Medio/microbiología , Exoma/genética , Femenino , Células HEK293 , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Microbiota/fisiología , Otitis Media/microbiología , Linaje , Galactósido 2-alfa-L-Fucosiltransferasa
3.
Hum Mutat ; 40(8): 1156-1171, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31009165

RESUMEN

A genetic basis for otitis media is established, however, the role of rare variants in disease etiology is largely unknown. Previously a duplication variant within A2ML1 was identified as a significant risk factor for otitis media in an indigenous Filipino population and in US children. In this report exome and Sanger sequencing was performed using DNA samples from the indigenous Filipino population, Filipino cochlear implantees, US probands, Finnish, and Pakistani families with otitis media. Sixteen novel, damaging A2ML1 variants identified in otitis media patients were rare or low-frequency in population-matched controls. In the indigenous population, both gingivitis and A2ML1 variants including the known duplication variant and the novel splice variant c.4061 + 1 G>C were independently associated with otitis media. Sequencing of salivary RNA samples from indigenous Filipinos demonstrated lower A2ML1 expression according to the carriage of A2ML1 variants. Sequencing of additional salivary RNA samples from US patients with otitis media revealed differentially expressed genes that are highly correlated with A2ML1 expression levels. In particular, RND3 is upregulated in both A2ML1 variant carriers and high-A2ML1 expressors. These findings support a role for A2ML1 in keratinocyte differentiation within the middle ear as part of otitis media pathology and the potential application of ROCK inhibition in otitis media.


Asunto(s)
Regulación hacia Abajo , Perfilación de la Expresión Génica/métodos , Mutación , Otitis Media/genética , Análisis de Secuencia de ADN/métodos , alfa-Macroglobulinas/genética , Adolescente , Adulto , Niño , Preescolar , Femenino , Finlandia , Regulación de la Expresión Génica , Predisposición Genética a la Enfermedad , Humanos , Lactante , Masculino , Persona de Mediana Edad , Pakistán , Linaje , Filipinas , Análisis de Secuencia de ARN , Transducción de Señal , Estados Unidos , Adulto Joven
4.
Nature ; 455(7212): 537-41, 2008 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-18754012

RESUMEN

Sensory hair cells in the mammalian cochlea convert mechanical stimuli into electrical impulses that subserve audition. Loss of hair cells and their innervating neurons is the most frequent cause of hearing impairment. Atonal homologue 1 (encoded by Atoh1, also known as Math1) is a basic helix-loop-helix transcription factor required for hair-cell development, and its misexpression in vitro and in vivo generates hair-cell-like cells. Atoh1-based gene therapy to ameliorate auditory and vestibular dysfunction has been proposed. However, the biophysical properties of putative hair cells induced by Atoh1 misexpression have not been characterized. Here we show that in utero gene transfer of Atoh1 produces functional supernumerary hair cells in the mouse cochlea. The induced hair cells display stereociliary bundles, attract neuronal processes and express the ribbon synapse marker carboxy-terminal binding protein 2 (refs 12,13). Moreover, the hair cells are capable of mechanoelectrical transduction and show basolateral conductances with age-appropriate specializations. Our results demonstrate that manipulation of cell fate by transcription factor misexpression produces functional sensory cells in the postnatal mammalian cochlea. We expect that our in utero gene transfer paradigm will enable the design and validation of gene therapies to ameliorate hearing loss in mouse models of human deafness.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Cóclea/citología , Cóclea/metabolismo , Células Ciliadas Auditivas/fisiología , Transfección , Útero , Animales , Cóclea/embriología , Cóclea/crecimiento & desarrollo , Cóclea/inervación , Sordera/genética , Sordera/terapia , Modelos Animales de Enfermedad , Dineínas/metabolismo , Conductividad Eléctrica , Femenino , Terapia Genética , Células Ciliadas Auditivas/citología , Humanos , Mecanotransducción Celular , Ratones , Miosina VIIa , Miosinas/metabolismo , Embarazo , Sinapsis/metabolismo
5.
Ann Otol Rhinol Laryngol ; 122(4): 269-72, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23697325

RESUMEN

OBJECTIVES: We describe the clinical evaluation and operative management of posterior semicircular canal dehiscence caused by a high jugular bulb. METHODS: We performed a retrospective case report. RESULTS: The patient had clinical and audiometric findings consistent with semicircular canal dehiscence and imaging findings that demonstrated erosion of the posterior semicircular canal by a high jugular bulb. Resurfacing of the eroded canal provided resolution of the vestibular symptoms without damage to the inner ear. CONCLUSIONS: Dehiscence of the posterior semicircular canal can cause clinical and audiometric findings similar to those of superior semicircular canal dehiscence syndrome. Resurfacing of the area of dehiscence can successfully relieve the vestibular symptoms. In the case of dehiscence of the posterior canal from a high jugular bulb, resurfacing may offer advantages over canal plugging for definitive management.


Asunto(s)
Venas Yugulares , Canales Semicirculares/cirugía , Acúfeno/cirugía , Vértigo/cirugía , Audiometría , Medidas del Movimiento Ocular , Humanos , Masculino , Estudios Retrospectivos , Canales Semicirculares/patología , Canales Semicirculares/fisiopatología , Acúfeno/etiología , Vértigo/etiología , Potenciales Vestibulares Miogénicos Evocados , Adulto Joven
6.
Otol Neurotol ; 44(2): e73-e80, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36624593

RESUMEN

HYPOTHESIS: To assess whether cochlear implant (CI)-related magnetic resonance imaging (MRI) artifact and visibility of the internal auditory canal (IAC) can be improved with head positioning and select MRI sequences. BACKGROUND: CI-related MRI artifact limits the use of CIs in otherwise good candidates because of the need for serial MRIs for monitoring of pathology. This most notably impacts patients with tumors of the cerebellopontine angle and IAC. METHODS: Two cadaver heads were implanted with either a Med-El CONCERT (fixed magnet) or SYNCHRONY (rotating magnet) device. Each head was imaged in a 1.5T scanner in 11 different positions. The SYNCHRONY-implanted head was also imaged in a 3.0T scanner in seven positions. Artifact size and IAC visibility (graded on a Likert scale) were measured for each head position by a neuroradiologist. RESULTS: The CONCERT CI produced significantly smaller artifact than the SYNCHRONY CI (effect size, 14.65 mm; p < 0.001). There was no significant difference between CI models in regard to IAC visibility. No head positions were statistically significantly better than neutral position for minimizing artifact size or IAC visibility, although some positions resulted in significantly larger artifact (effect sizes, 2.1-14.3 mm; p < 0.05) or significantly poorer IAC visibility (effect size, 1.4; p < 0.01). The T2 three-dimensional (CISS/FIESTA) sequence demonstrated significantly smaller artifact than T1 sequences, whereas T1 sequences demonstrated significantly better IAC visibility than T2 sequences. CONCLUSION: Head positioning and magnetic resonance sequence selection impact CI-related artifact size and IAC visibility.


Asunto(s)
Implantación Coclear , Implantes Cocleares , Humanos , Artefactos , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética
7.
Ann Otol Rhinol Laryngol ; 132(12): 1686-1689, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37243327

RESUMEN

INTRODUCTION: Aminoglycoside antibiotics such as gentamicin are bactericidal and effective against gram negative organisms and act synergistically against gram positive organisms, including Staphylococcus aureus. However, they have serious adverse effects such as nephrotoxicity and ototoxicity. Gentamicin ototoxicity may occur after a single dose and results in decreased vestibular function, which is frequently debilitating and often permanent. OBJECTIVE: To emphasize the risk of gentamicin ototoxicity and suggest alternative antibiotics in penicillin-allergic patients undergoing surgery. CASE SUMMARY: We present a case of a woman with preexisting Meniere's Disease who received gentamicin 400 mg perioperatively for a sigmoidectomy due to a penicillin allergy listed in the patient's medical record. The patient developed severe ototoxicity preventing her from working or driving. Physical examination was remarkable for a broad-based gait requiring assistance to walk and bilateral corrective saccades. Vestibular testing revealed high-grade bilateral vestibular loss associated with all semicircular canals, a considerable decline compared to her function 3 years prior. DISCUSSION: Gentamicin is indicated for surgical prophylaxis when a patient has a true allergy to penicillins and cannot receive cephalosporins, though alternatives exist. True allergies include IgE-mediated illness (anaphylaxis, bronchospasm, or urticaria 30-60 minutes after administration) or exfoliative reactions (Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis). The authors encourage more prudent use of gentamicin, especially in patients susceptible for debilitating otologic insults, and offer recommendations for alternative agents prior to using gentamicin.


Asunto(s)
Gentamicinas , Ototoxicidad , Femenino , Humanos , Antibacterianos/efectos adversos , Gentamicinas/efectos adversos , Hipersensibilidad , Ototoxicidad/etiología , Penicilinas/efectos adversos
8.
Otolaryngol Head Neck Surg ; 168(3): 462-468, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-35671134

RESUMEN

OBJECTIVE: Sensorineural hearing loss is a known complication of stapes surgery. We previously showed that laser stapedotomy can result in intracochlear pressures that are comparable to high sound pressure levels. Optimizing laser settings to those that correspond with the lowest pressure changes may mitigate risk for postoperative hearing loss. Here we quantify the effects of various laser parameters on intracochlear pressures and test the hypothesis that intracochlear pressure changes are proportional to the laser energy delivered. STUDY DESIGN: Basic and translational science. SETTING: Cadaveric dissection and basic science laboratory. METHODS: Cadaveric human heads underwent mastoidectomies. Intracochlear pressures were measured via fiber-optic pressure probes placed in scala vestibuli and tympani. Pulses of varied stimulus power and duration from a 980-nm diode laser were applied to the stapes footplate. RESULTS: Sustained high-intensity pressures were observed in the cochlea during all laser applications. Observed pressure magnitudes increased monotonically with laser energy and rose linearly for lower stimulus durations and powers, but there was increased variability for laser applications of longer duration (200-300 ms) and/or higher power (8 W). CONCLUSIONS: Results confirm that significant pressure changes occur during laser stapedotomy, which we hypothesize may cause injury. Overall energy delivered depends predictably on duration and power, but surgeons should use caution at the highest stimulus levels and longest pulse durations due to the increasing variability in intracochlear pressure under these stimulus conditions. While the risk to hearing from increased intracochlear pressures from laser stapedotomy remains unclear, these results affirm the need to optimize laser settings to avoid unintended injury.


Asunto(s)
Terapia por Láser , Cirugía del Estribo , Humanos , Cóclea/cirugía , Audición , Rayos Láser , Cadáver , Terapia por Láser/efectos adversos
9.
Genes (Basel) ; 14(4)2023 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-37107589

RESUMEN

Vertigo due to vestibular dysfunction is rare in children. The elucidation of its etiology will improve clinical management and the quality of life of patients. Genes for vestibular dysfunction were previously identified in patients with both hearing loss and vertigo. This study aimed to identify rare, coding variants in children with peripheral vertigo but no hearing loss, and in patients with potentially overlapping phenotypes, namely, Meniere's disease or idiopathic scoliosis. Rare variants were selected from the exome sequence data of 5 American children with vertigo, 226 Spanish patients with Meniere's disease, and 38 European-American probands with scoliosis. In children with vertigo, 17 variants were found in 15 genes involved in migraine, musculoskeletal phenotypes, and vestibular development. Three genes, OTOP1, HMX3, and LAMA2, have knockout mouse models for vestibular dysfunction. Moreover, HMX3 and LAMA2 were expressed in human vestibular tissues. Rare variants within ECM1, OTOP1, and OTOP2 were each identified in three adult patients with Meniere's disease. Additionally, an OTOP1 variant was identified in 11 adolescents with lateral semicircular canal asymmetry, 10 of whom have scoliosis. We hypothesize that peripheral vestibular dysfunction in children may be due to multiple rare variants within genes that are involved in the inner ear structure, migraine, and musculoskeletal disease.


Asunto(s)
Sordera , Enfermedad de Meniere , Trastornos Migrañosos , Escoliosis , Adulto , Adolescente , Niño , Animales , Ratones , Humanos , Calidad de Vida , Escoliosis/complicaciones , Vértigo , Sordera/complicaciones , Trastornos Migrañosos/genética , Trastornos Migrañosos/complicaciones , Proteínas de la Matriz Extracelular
10.
Ann Otol Rhinol Laryngol ; 121(8): 521-4, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22953658

RESUMEN

OBJECTIVES: We seek to describe an individual with bilateral duplicated internal carotid arteries (ICAs) presenting as middle ear masses, to discuss the anatomy and characteristic imaging findings associated with this condition, and to familiarize clinicians with effective methods to prevent and manage complications related to this entity. METHODS: The clinical presentation of an individual with this unusual vascular anomaly was reviewed. A literature search was then performed to identify previously reported studies describing aberrant ICAs in order to characterize the presentation, anatomy, imaging findings, and management of this condition. RESULTS: An aberrant ICA presenting as a middle ear mass is uncommon; there are only approximately 45 reported cases to date. The majority of these cases presented as a unilateral anomaly without a duplication, were associated with pulsatile tinnitus and hearing loss, and were diagnosed during middle ear procedures. Bilateral aberrant ICAs are exceedingly rare, with only 14 existing reports. Only 1 of these cases presented with duplicated ICAs. Our report demonstrates an unusual presentation of aberrant ICAs, as pulsatile tinnitus was absent and previous middle ear surgery had been performed without establishing this diagnosis and without any resulting complications. Furthermore, this case represents the first known instance of a bilateral duplicated ICA system without persistent stapedial arteries. Although vascular middle ear anomalies are unusual, complications of surgical manipulation have been documented. CONCLUSIONS: The clinician must have a high index of suspicion for vascular lesions in patients presenting with a retrotympanic mass. Appropriate diagnostic imaging studies should be performed to exclude this diagnosis before middle ear exploration. Should injury to the carotid artery occur, surgeons should follow specific guidelines to avoid potentially serious complications.


Asunto(s)
Arteria Carótida Interna/anomalías , Adolescente , Arteria Carótida Interna/patología , Audífonos , Perdida Auditiva Conductiva-Sensorineural Mixta/etiología , Perdida Auditiva Conductiva-Sensorineural Mixta/terapia , Humanos , Imagenología Tridimensional , Angiografía por Resonancia Magnética , Masculino , Otitis Media/complicaciones , Otitis Media/cirugía , Tomografía Computarizada por Rayos X
11.
Neurosurg Focus ; 33(3): E11, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22937845

RESUMEN

Of the presigmoid approaches, the translabyrinthine approach is often used when a large exposure is needed to gain access to the cerebellopontine angle but when hearing preservation is not a concern. At the authors' institution, this approach is done with the aid of ENT/otolaryngology for temporal bone drilling and exposure. In the present article and video, the authors demonstrate the use of the translabyrinthine approach for resection of a large cystic vestibular schwannoma, delineating the steps of positioning, opening, temporal bone drilling, tumor resection, and closure. Gross-total resection was achieved in the featured case. The patient's postoperative facial function was House-Brackmann Grade II on the side ipsilateral to the tumor, although function improved with time. The translabyrinthine route to the cerebellopontine angle is an excellent approach for masses that extend toward the midline or anterior to the pons. Although hearing is sacrificed, facial nerve function is generally spared.


Asunto(s)
Quistes del Sistema Nervioso Central/cirugía , Neuroma Acústico/cirugía , Procedimientos Neuroquirúrgicos/métodos , Hueso Temporal/cirugía , Vestíbulo del Laberinto/cirugía , Quistes del Sistema Nervioso Central/complicaciones , Humanos , Imagen por Resonancia Magnética , Neuroma Acústico/complicaciones , Neuroma Acústico/patología , Estudios Retrospectivos , Resultado del Tratamiento
12.
Front Genet ; 13: 1033965, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36699445

RESUMEN

Cholesteatoma is a rare and benign disease, but its propensity to cause erosive damage through uninhibited growth can be detrimental to hearing and health. Prior reports indicated a genetic component to pathogenesis in at least a subset of patients. In this study, we aimed to identify rare DNA variants in affected patients. The salivary DNA of six patients whose middle ear tissues were obtained during tympanoplasty/mastoidectomy surgeries were submitted for exome sequencing. Tissue samples from the same patients were previously submitted for mRNA sequencing and analyzed for differentially expressed genes (DEGs). From the generated exome sequence data, rare predicted-to-be-damaging variants were selected within previously identified DEGs, and the candidate genes within which these rare variants lie were used for network analysis. Exome sequencing of six DNA samples yielded 5,078 rare variants with minor allele frequency <.001. A total of 510 variants were predicted to be deleterious and 52 were found to lie within previously identified DEGs. After selecting variants based on quality control measures, 12 variants were identified all from one pediatric patient. Network analysis identified ten significant cellular pathways, including protein transport, viral process, regulation of catalytic activity and cell cycle, and apoptotic and rhythmic processes. We hypothesize that the candidate genes identified in this study may be part of key signaling pathways during the mucosal response to middle ear infection. The occurrence of multiple rare variants may play a role in earlier onset of cholesteatoma formation in chronic otitis media.

13.
Hear Res ; 404: 108215, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33677192

RESUMEN

Efferent innervation of the inner hair cells changes over time. At an early age in mice, inner hair cells receive efferent feedback, which helps fine-tune tonotopic maps in the brainstem. In adulthood, inner hair cell efferent innervation wanes but increases again in older animals. It is not clear, however, whether age-related inner hair cell efferents increase along the entire range of the cochlear frequencies, or if this increase is restricted to a particular frequency-region, and whether this phenomenon occurs in both sexes. Age-related hearing loss, presbycusis, affects men and women differently. In mice, this difference is also strain specific. In aging black six mice, the auditory brainstem response thresholds increase in females earlier than in males. Here, we study age-related increase of the inner hair cell efferent innervation throughout the cochlea before hearing onset, in one month old and in ten months old and older male and female black six mice. We collected confocal images of immunostained inner hair cell efferents and quantified the labeled terminals in the entire cochlea using a machine learning algorithm. The overall number of the inner hair cell efferents in both sexes did not change significantly between age-groups. The distribution of the inner hair cell efferent innervation did not differ across frequencies in the cochlea. However, in females, inner hair cells received on average up to four times more efferent innervation than in males per each of the frequency regions tested. Sex differences were also found in the oldest age-group tested (≥ 10 months) where on average inner hair cells received six times more efferents in females than in males of matching age. Our findings emphasize the importance of including both sexes in sensorineural hearing loss research.


Asunto(s)
Células Ciliadas Auditivas Internas , Caracteres Sexuales , Envejecimiento , Animales , Cóclea , Femenino , Masculino , Ratones , Neuronas Eferentes , Sinapsis
14.
Stem Cell Res Ther ; 12(1): 352, 2021 06 19.
Artículo en Inglés | MEDLINE | ID: mdl-34147129

RESUMEN

BACKGROUND: Hearing loss affects 25% of the population at ages 60-69 years. Loss of the hair cells of the inner ear commonly underlies deafness and once lost this cell type cannot spontaneously regenerate in higher vertebrates. As a result, there is a need for the development of regenerative strategies to replace hair cells once lost. Stem cell-based therapies are one such strategy and offer promise for cell replacement in a variety of tissues. A number of investigators have previously demonstrated successful implantation, and certain level of regeneration of hair and supporting cells in both avian and mammalian models using rodent pluripotent stem cells. However, the ability of human stem cells to engraft and generate differentiated cell types in the inner ear is not well understood. METHODS: We differentiate human pluripotent stem cells to the pre-placodal stage in vitro then transplant them into the mouse cochlea after selective and complete lesioning of the endogenous population of hair cells. RESULTS: We demonstrate that hair cell ablation prior to transplantation leads to increased engraftment in the auditory sensory epithelium, the organ of Corti, as well as differentiation of transplanted cells into hair and supporting cell immunophenotypes. CONCLUSION: We have demonstrated the feasibility of human stem cell engraftment into an ablated mouse organ of Corti.


Asunto(s)
Células Madre Embrionarias Humanas , Células Madre Pluripotentes , Animales , Diferenciación Celular , Cóclea , Células Ciliadas Auditivas , Humanos , Ratones , Trasplante de Células Madre
15.
Ann Otol Rhinol Laryngol ; 130(11): 1213-1219, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33813907

RESUMEN

OBJECTIVE: To describe a case of benign paroxysmal positional vertigo (BPPV) resulting in reversible horizontal semicircular canalith jam successfully treated with horizontal canal occlusion. A brief literature review of similar cases was performed. METHODS: Case report and literature review. RESULTS: A 68-year-old female presented with apogeotropic positional nystagmus, attributed to reversible horizontal canalith jam mimicking cupulolithiasis that was refractory to tailored repositioning maneuvers across months. She was unable to work due to the severity of her symptoms. She underwent surgical occlusion of the affected canal with immediate resolution of her symptoms. A literature review revealed similar cases of canalith jam mimicking cupulolithiasis. CONCLUSIONS: Reversible canalith jam, in which particles moving with horizontal head position alternate between obstructing the semicircular canal and resting on the cupula, can mimic signs of cupulolithiasis. This variant of BPPV can be effectively managed with surgical canal occlusion should symptoms fail to resolve after tailored repositioning maneuvers.


Asunto(s)
Vértigo Posicional Paroxístico Benigno , Laberintitis , Membrana Otolítica , Canales Semicirculares , Enfermedades Vestibulares/diagnóstico , Anciano , Vértigo Posicional Paroxístico Benigno/diagnóstico , Vértigo Posicional Paroxístico Benigno/etiología , Vértigo Posicional Paroxístico Benigno/fisiopatología , Vértigo Posicional Paroxístico Benigno/cirugía , Diagnóstico Diferencial , Técnicas de Diagnóstico Otológico , Femenino , Humanos , Laberintitis/diagnóstico , Laberintitis/fisiopatología , Laberintitis/cirugía , Litiasis/diagnóstico , Membrana Otolítica/patología , Membrana Otolítica/fisiopatología , Procedimientos Quirúrgicos Otológicos/métodos , Canales Semicirculares/patología , Canales Semicirculares/cirugía , Resultado del Tratamiento
16.
Front Cell Infect Microbiol ; 11: 798246, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35096646

RESUMEN

Otitis media (OM) is a leading cause of childhood hearing loss. Variants in FUT2, which encodes alpha-(1,2)-fucosyltransferase, were identified to increase susceptibility to OM, potentially through shifts in the middle ear (ME) or nasopharyngeal (NP) microbiotas as mediated by transcriptional changes. Greater knowledge of differences in relative abundance of otopathogens in carriers of pathogenic variants can help determine risk for OM in patients. In order to determine the downstream effects of FUT2 variation, we examined gene expression in relation to carriage of a common pathogenic FUT2 c.461G>A (p.Trp154*) variant using RNA-sequence data from saliva samples from 28 patients with OM. Differential gene expression was also examined in bulk mRNA and single-cell RNA-sequence data from wildtype mouse ME mucosa after inoculation with non-typeable Haemophilus influenzae (NTHi). In addition, microbiotas were profiled from ME and NP samples of 65 OM patients using 16S rRNA gene sequencing. In human carriers of the FUT2 variant, FN1, KMT2D, MUC16 and NBPF20 were downregulated while MTAP was upregulated. Post-infectious expression in the mouse ME recapitulated these transcriptional differences, with the exception of Fn1 upregulation after NTHi-inoculation. In the NP, Candidate Division TM7 was associated with wildtype genotype (FDR-adj-p=0.009). Overall, the FUT2 c.461G>A variant was associated with transcriptional changes in processes related to response to infection and with increased load of potential otopathogens in the ME and decreased commensals in the NP. These findings provide increased understanding of how FUT2 variants influence gene transcription and the mucosal microbiota, and thus contribute to the pathology of OM.


Asunto(s)
Fucosiltransferasas , Infecciones por Haemophilus , Microbiota , Nasofaringe , Otitis Media , Animales , Oído Medio , Fucosiltransferasas/genética , Infecciones por Haemophilus/metabolismo , Haemophilus influenzae/genética , Humanos , Ratones , Microbiota/genética , Nasofaringe/microbiología , Otitis Media/genética , Otitis Media/metabolismo , ARN Ribosómico 16S/genética , Galactósido 2-alfa-L-Fucosiltransferasa
17.
Hear Res ; 394: 107934, 2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32204962

RESUMEN

The application of gene therapy is widely expanding in research and continuously improving in preparation for clinical applications. The inner ear is an attractive target for gene therapy for treating environmental and genetic diseases in both the auditory and vestibular systems. With the lack of spontaneous cochlear hair cell replacement, hair cell regeneration in adult mammals is among the most important goals of gene therapy. In addition, correcting gene defects can open up a new era for treating inner ear diseases. The relative isolation and small size of the inner ear dictate local administration routes and carefully calculated small volumes of reagents. In the current review, we will cover effective timing, injection routes and types of vectors for successful gene delivery to specific target cells within the inner ear. Differences between research purposes and clinical applications are also discussed.


Asunto(s)
Oído Interno , Enfermedades del Laberinto , Terapia Genética , Células Ciliadas Auditivas , Humanos , Enfermedades del Laberinto/genética , Enfermedades del Laberinto/terapia , Sistema Vestibular
18.
Ann Otol Rhinol Laryngol ; 129(11): 1135-1143, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32486832

RESUMEN

BACKGROUND: Recommendations regarding head and neck paragangliomas (HNPGL) have undergone a fundamental reorientation in the last decade as a result of increased understanding of the genetic and pathophysiologic basis of these disorders. OBJECTIVE: We aim to provide an overview of HNPGL and recent discoveries regarding their molecular genetics, along with updated recommendations on workup, treatment, and surveillance, and their implications for otolaryngologists treating patients with these disorders. RESULTS: SDHx susceptibility gene mutations, encoding subunits of the enzyme succinate dehydrogenase (SDH), give rise to the Hereditary Pheochromocytoma/Paraganglioma Syndromes. SDHA, SDHB, SDHC, SDHD, and SDHAF2 mutations each result in unique phenotypes with distinct penetrance and risk for variable tumor development as well as metastasis. Genetic and biochemical testing is recommended for every patient with HNPGL. Multifocal disease should be managed in multi-disciplinary fashion. Patients with SDHx mutations require frequent biochemical screening and whole-body imaging, as well as lifelong follow-up with an expert in hereditary pheochromocytoma and paraganglioma syndromes. CONCLUSION: Otolaryngologists are likely to encounter patients with HNPGL. Keeping abreast of the latest recommendations, especially regarding genetic testing, workup for additional tumors, multi-disciplinary approach to care, and need for lifelong surveillance, will help otolaryngologists appropriately care for these patients.


Asunto(s)
Neoplasias de Cabeza y Cuello/genética , Proteínas de la Membrana/genética , Mutación , Otorrinolaringólogos , Paraganglioma/genética , Pruebas Genéticas , Neoplasias de Cabeza y Cuello/metabolismo , Humanos , Proteínas de la Membrana/metabolismo , Paraganglioma/metabolismo , Fenotipo
19.
Otol Neurotol ; 41(3): 308-317, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31746814

RESUMEN

HYPOTHESIS: Surgical manipulations during laser stapedotomy can produce intracochlear pressure changes comparable to pressures created by high-intensity acoustic stimuli. BACKGROUND: New-onset sensorineural hearing loss is a known risk of stapes surgery and may result from pressure changes from laser use or other surgical manipulations. Here, we test the hypothesis that high sound pressure levels are generated in the cochlea during laser stapedotomy. METHODS: Human cadaveric heads underwent mastoidectomy. Fiber-optic sensors were placed in scala tympani and vestibuli to measure intracochlear pressures during key steps in stapedotomy surgery, including cutting stapedius tendon, lasering of stapedial crurae, crural downfracture, and lasering of the footplate. RESULTS: Key steps in laser stapedotomy produced high-intensity pressures in the cochlea. Pressure transients were comparable to intracochlear pressures measured in response to high intensity impulsive acoustic stimuli. CONCLUSION: Our results demonstrate that surgical manipulations during laser stapedotomy can create significant pressure changes within the cochlea, suggesting laser application should be minimized and alternatives to mechanical downfracture should be investigated. Results from this investigation suggest that intracochlear pressure transients from stapedotomy may be of sufficient magnitude to cause damage to the sensory epithelium and affirm the importance of limiting surgical traumatic exposures.


Asunto(s)
Terapia por Láser , Cirugía del Estribo , Cóclea/cirugía , Oído Medio , Humanos , Terapia por Láser/efectos adversos , Rayos Láser , Rampa Timpánica , Cirugía del Estribo/efectos adversos
20.
Otol Neurotol ; 41(5): 679-685, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32150025

RESUMEN

OBJECTIVE: To determine short- and intermediate-term hearing preservation rates after microsurgical resection of vestibular schwannoma (VS). DATA SOURCES: Systematic review of the Ovid, Cochrane, EMBASE, and Web of Science databases. STUDY SELECTION: This study was restricted to full-text English-language articles detailing VS resection via the middle cranial fossa or retrosigmoid approaches. Documentation of pre- and posttreatment hearing outcomes with American Academy of Otolaryngology-Head and Neck Surgery, Gardner-Robertson, or word recognition score scales, as well as time to follow-up were required. Duplicate data sets, studies with >10% of patients with neurofibromatosis two, previous or nonsurgical VS treatment, case reports with

Asunto(s)
Neuroma Acústico , Fosa Craneal Media/cirugía , Audición , Pruebas Auditivas , Humanos , Microcirugia , Neuroma Acústico/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
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