RESUMEN
OBJECTIVE: Cleft palate (CP) in children is frequently complicated by otitis media with effusion (OME) due to Eustachian tube dysfunction. Although tympanostomy tube (TT) placement can be beneficial in the treatment of OME to prevent short-term hearing loss, there is no consensus regarding the indications for and timing of TT insertion. The present study was performed to define the safety and effectiveness of simultaneous TT placement with palatoplasty during the language-acquisition period. METHODS: We retrospectively reviewed the medical charts of pediatric patients who underwent palatoplasty for CP in a tertiary medical center, Kyoto University Hospital, from June 2010 to October 2018. The TT retention time was estimated using the Kaplan-Meier method. The incidence of OME recurrence was compared among four Veau classification groups based on the patients' sex, type of CP, median TT retention time, and type of fluid. RESULTS: Seventy-six subjects (150 ears) were enrolled in the study. The median follow-up duration was 48.7 months (range, 18.2-108.0 months) after the first TT placement. A first TT retention time of <20.1 months was a significant risk factor for OME recurrence. Subjects with maxillofacial anomaly complex and subjects with cleft lip and palate and an alveolar cleft showed a significantly higher OME recurrence rate than subjects with clefts only in the hard and/or soft palate. There was no significant difference in the occurrence of sequelae between subjects with only a single TT placement and subjects with more than one TT placement. CONCLUSIONS: Based on the findings of the present study, it is reasonable to perform TT insertion at the same time as palatoplasty on patients who meet the indications. This technique may reduce the number of times the patient requires general anesthesia and maintain good middle ear condition during the period of language acquisition between 1 and 3 years of age.
Asunto(s)
Labio Leporino , Fisura del Paladar , Otitis Media con Derrame , Niño , Labio Leporino/cirugía , Fisura del Paladar/complicaciones , Fisura del Paladar/cirugía , Humanos , Lactante , Lenguaje , Desarrollo del Lenguaje , Ventilación del Oído Medio/efectos adversos , Otitis Media con Derrame/complicaciones , Otitis Media con Derrame/epidemiología , Otitis Media con Derrame/cirugía , Paladar Blando , Pronóstico , Estudios RetrospectivosRESUMEN
The OTOF gene (Locus: DFNB9), encoding otoferlin, is reported to be one of the major causes of non-syndromic recessive sensorineural hearing loss, and is also reported to be the most common cause of non-syndromic recessive auditory neuropathy spectrum disorder (ANSD). In the present study, we performed OTOF mutation analysis using massively parallel DNA sequencing (MPS). The purpose of this study was to reveal the frequency and precise genetic and clinical background of OTOF-related hearing loss in a large hearing loss population. A total of 2,265 Japanese sensorineural hearing loss (SNHL) patients compatible with autosomal recessive inheritance (including sporadic cases) from 53 otorhinolaryngology departments nationwide participated in this study. The mutation analysis of 68 genes, including the OTOF gene, reported to cause non-syndromic hearing loss was performed using MPS. Thirty-nine out of the 2,265 patients (1.72%) carried homozygous or compound heterozygous mutations in the OTOF gene. It is assumed that the frequency of hearing loss associated with OTOF mutations is about 1.72% of autosomal recessive or sporadic SNHL cases. Hearing level information was available for 32 of 39 patients with biallelic OTOF mutations; 24 of them (75.0%) showed profound hearing loss, 7 (21.9%) showed severe hearing loss and 1 (3.1%) showed mild hearing loss. The hearing level of patients with biallelic OTOF mutations in this study was mostly severe to profound, which is consistent with the results of past reports. Eleven of the 39 patients with biallelic OTOF mutations had been diagnosed with ANSD. The genetic diagnosis of OTOF mutations has significant benefits in terms of clinical decision-making. Patients with OTOF mutations would be good candidates for cochlear implantation; therefore, the detection of OTOF mutations is quite beneficial for patients, especially for those with ANSD.
Asunto(s)
Análisis Mutacional de ADN , Pérdida Auditiva Sensorineural/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Proteínas de la Membrana/genética , Mutación , Adulto , Femenino , Pérdida Auditiva Sensorineural/diagnóstico , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Hearing impairment is one of the most common sensory disorders that affect ~1 in 1000 children, and half of them are considered to be hereditary. Information about the carrier frequencies of mutations that underlie autosomal recessive disorders is indispensable for accurate genetic counseling to predict the probability of patients' children's disease. However, there have been few reports specific to the Japanese population. GJB2 mutations are reported to be the most frequent cause of hereditary hearing loss, and the mutation spectrum and frequency of GJB2 mutations were reported to vary among different ethnic groups. In this study, we investigated the carrier frequency of GJB2 mutations and the mutation spectrum in 509 individuals randomly selected from the general Japanese population. We show that the carrier frequencies of the two most common pathogenic mutations are 1.57% (8/509) for c.235delC and 1.77% (9/509) for p.Val37Ile. In addition to these mutations, we found two pathogenic variants (p.[Gly45Glu;Tyr136*] and p.Arg143Trp), and the total carrier frequency was estimated to be around 3.73% (19/509). We also detected six unclassified variants, including two novel variants (p.Cys60Tyr and p.Phe106Leu), with the former predicted to be pathogenic. These findings will provide indispensable information for genetic counseling in the Japanese population.
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Pueblo Asiatico/genética , Conexinas/genética , Frecuencia de los Genes , Pérdida Auditiva/genética , Adulto , Anciano , Anciano de 80 o más Años , Conexina 26 , Femenino , Pérdida Auditiva/epidemiología , Humanos , Japón/epidemiología , Masculino , Persona de Mediana EdadRESUMEN
Cisplatin is a widely used chemotherapeutic agent for the treatment of various malignancies. However, its maximum dose is often limited by severe ototoxicity. Cisplatin ototoxicity may require the production of reactive oxygen species (ROS) in the inner ear by activating enzymes specific to the cochlea. Molecular hydrogen was recently established as an antioxidant that selectively reduces ROS, and has been reported to protect the central nervous system, liver, kidney and cochlea from oxidative stress. The purpose of this study was to evaluate the potential of molecular hydrogen to protect cochleae against cisplatin. We cultured mouse cochlear explants in medium containing various concentrations of cisplatin and examined the effects of hydrogen gas dissolved directly into the media. Following 48-h incubation, the presence of intact auditory hair cells was assayed by phalloidin staining. Cisplatin caused hair cell loss in a dose-dependent manner, whereas the addition of hydrogen gas significantly increased the numbers of remaining auditory hair cells. Additionally, hydroxyphenyl fluorescein (HPF) staining of the spiral ganglion showed that formation of hydroxyl radicals was successfully reduced in hydrogen-treated cochleae. These data suggest that molecular hydrogen can protect auditory tissues against cisplatin toxicity, thus providing an additional strategy to protect against drug-induced inner ear damage.
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Antineoplásicos/toxicidad , Cisplatino/antagonistas & inhibidores , Cisplatino/toxicidad , Radicales Libres/toxicidad , Células Ciliadas Auditivas/efectos de los fármacos , Hidrógeno/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Enfermedades Cocleares/inducido químicamente , Enfermedades Cocleares/prevención & control , Relación Dosis-Respuesta a Droga , Gases , Ratones , Ratones Endogámicos ICR , Especies Reactivas de Oxígeno/metabolismo , Ganglio Espiral de la Cóclea/efectos de los fármacos , Ganglio Espiral de la Cóclea/metabolismoRESUMEN
HYPOTHESIS: Cochlear pathology can be evaluated in living animals using optical coherence tomography (OCT). BACKGROUND: The current imaging methods available for the detailed analysis of cochlear pathology in a clinical setting provide only limited information. Thus, a cochlear imaging modality with high definition is needed for improving the diagnosis of cochlear pathology. OCT has been used in other fields for obtaining high-resolution subsurface images, and its use could potentially be extended to the analysis of cochlear pathogenesis. METHODS: Slc26a4(-/-) mice, which generate endolymphatic hydrops, and their littermates were used in this study. Auditory function was monitored by the auditory brainstem responses (ABR). After the mice were placed under general anesthesia, OCT images of the cochlea were captured. The cochlea was subsequently dissected out and histologically evaluated. Three or 7 days later, the wild-type mice cochleae were visualized again. RESULTS: In ABR assessments, Slc26a4(-/-) mice showed severe hearing loss, while no significant hearing loss was found in Slc26a4(+/-) or Slc26a4(+/+) mice. OCT demonstrated normal morphology in the cochlea of both Slc26a4(+/-) and Slc26a4(+/+) mice, including the location of Reissner's membrane. Meanwhile, in Slc26a4(-/-) mice, obvious dislocation of Reissner's membrane was observed, indicating severe endolymphatic hydrops. These findings in the OCT images were consistent with the histologic results for the cochlear morphology, as observed with hematoxylin and eosin staining. Three or 7 days later, wild-type cochleae were successfully visualized using OCT, and no otitis media or labyrinthitis was observed. CONCLUSION: OCT can be applied in the detection of endolymphatic hydrops in living mice, indicating the potential of OCT for cochlear imaging analyses for clinical use in the near future.
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Cóclea/patología , Hidropesía Endolinfática/patología , Pérdida Auditiva/patología , Tomografía de Coherencia Óptica/métodos , Animales , Cóclea/fisiopatología , Hidropesía Endolinfática/fisiopatología , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Pérdida Auditiva/fisiopatología , RatonesRESUMEN
Newborn hearing screening (NHS) has been conducted widely in Japan in the last decade, however, there seems to be some confusion regarding the significance of NHS or management of the results obtained from NHS among clinics and practitioners. The system of NHS in Japan should be improved and refined through continuous evaluation of NHS, in terms of cost effectiveness in particular, so that NHS can be conducted more efficiently and effectively. To achieve this goal, the authors thought it important to clarify the current status and roles of our department as a facility for infants with congenital hearing impairment. In the present study, we studied 106 infant cases who were referred to the Department of Otolaryngology in Kyoto University Hospital after NHS before the age of twelve months in a period of seven years from 2006 to 2012 via retrospective chart reviewing. 79.2% of 96 infants who were qualified as referred either unilaterally or bilaterally following NHS were diagnosed as having hearing impairment in any form, either unilateral or bilateral, or conductive and/or sensorineural. The positive agreement rate was 88.7% in 53 cases who were qualified as referred bilaterally in NHS, demonstrating a high reliability of the NHS system. Twenty-four cases were diagnosed as having the need for hearing aids and were assigned to treatment and education. All the infants who underwent cochlear implantation in our department had severe bilateral hearing impairment of more than 105 dBnHL in both ears at the first examination. Moreover, a number of infants who were qualified as having passed in both ears in NHS or who had failed to receive NHS at birth were revealed as having hearing impairment and needed treatment later in the first year of their life, suggesting that NHS should be conducted in combination with periodical health checkups by family practitioners in order to identify infants with hearing impairment earlier in their life with higher efficacy.
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Tamizaje Neonatal , Trastornos de la Audición/congénito , Trastornos de la Audición/diagnóstico , Humanos , Lactante , Recién NacidoRESUMEN
Mammalian cochlear sensory epithelial cells are believed to possess minimal regenerative potential because they halt proliferation during late stage of embryogenesis and never regenerate after birth. This means that sensorineural hearing loss caused by the death of cochlear sensory epithelial cells is a permanent condition. However, stem cells were recently identified in neonatal mice following dissociation of their inner ear organs. This suggests that regenerative therapy for sensorineural hearing loss may be possible. Unfortunately, dissociation distorts the microanatomy of the inner ear, making it difficult to determine the precise location of stem cells in unaltered specimens. To develop new therapeutic approaches based on sensory epithelial cell regeneration, the location of these stem cells must be elucidated. Stem cells normally proliferate at a slow rate in adult organs. In fact, so-called label-retaining cells, or slow-cycling cells, of the brain and skin are recognized as stem cells. In this study, using the exogenous proliferation marker, 5'-bromo-2'-deoxyuridine (BrdU) in combination with the endogenous proliferation marker Ki-67, we identified tympanic border cells. These cells, which are located beneath the basilar membrane in vivo, represent slow-cycling cells of the murine cochlea. Immunohistochemically, these cells stained positive for the immature cell marker Nestin. But it will be difficult to achieve regeneration of the cochlear function because these slow-cycling cells disappear in the mature murine cochlea.