Publications by authors named "Henry C Ou"

Drug-induced hearing injury (ototoxicity) is a common, debilitating side effect of many antibiotic regimens that can be worsened by adverse drug interactions. Such adverse drug interactions are often not detected until after drugs are already on the market because of the difficulty of measuring all possible drug combinations. While in vivo mammalian assays to screen for ototoxic damage exist, they are currently time-consuming, costly, and limited in throughput, which limits their utility in assessing drug interaction outcomes.

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Ototoxicity is a debilitating side effect of over 150 medications with diverse mechanisms of action, many of which could be taken concurrently to treat multiple conditions. Approaches for preclinical evaluation of drug-drug interactions that might impact ototoxicity would facilitate design of safer multi-drug regimens and mitigate unsafe polypharmacy by flagging combinations that potentially cause adverse interactions for monitoring. They may also identify protective agents that antagonize ototoxic injury.

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Ototoxicity is a debilitating side effect of over 150 medications with diverse mechanisms of action, many of which could be taken concurrently to treat multiple conditions. Approaches for preclinical evaluation of drug interactions that might impact ototoxicity would facilitate design of safer multi-drug regimens and mitigate unsafe polypharmacy by flagging combinations that potentially cause adverse interactions for monitoring. They may also identify protective agents that antagonize ototoxic injury.

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Importance: In the US, most childhood-onset bilateral sensorineural hearing loss is genetic, with more than 120 genes and thousands of different alleles known. Primary treatments are hearing aids and cochlear implants. Genetic diagnosis can inform progression of hearing loss, indicate potential syndromic features, and suggest best timing for individualized treatment.

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Purpose: The purpose of this study is to provide updated national estimates on the annual number, educational environments, and secondary school outcomes of students who are D/deaf and hard of hearing (D/HH) receiving special education (SpEd) and related services in the United States.

Method: We performed a retrospective cross-sectional descriptive analysis of Individuals with Disabilities Education Act, Part B, Section 618 data from 2012 to 2018. Participants included students 6-21 years old in SpEd with "hearing impairment" reported as their primary disability.

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Article Synopsis
  • - The study focuses on how well otolaryngology-head and neck surgery (OHNS) and audiology trainees understand Deaf culture, which is important for reducing health disparities in Deaf patients.
  • - A survey conducted among trainees from 10 large U.S. institutions showed that while 97.8% were aware of Deaf culture, their average knowledge score was 55%, better than general practitioners (43%) but lower than medical students specifically trained in Deaf culture (69%).
  • - The results suggest that OHNS and audiology trainees have some awareness of Deaf culture, but there is a need for more focused educational efforts to enhance their understanding and sensitivity.
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Unlabelled: Our goal was to standardize intraoperative analgesic regimens for pediatric ambulatory tonsillectomy by eliminating local anesthetic use and to determine its impact on postoperative pain measures, while controlling for other factors.

Methods: We assembled a quality improvement team at an ambulatory surgery center. They introduced a standardized anesthetic protocol, involving American Society of Anesthesiologists Classification 1 and 2 patients undergoing adenotonsillectomy.

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Objectives: Cochlear implant depth of insertion affects audiologic outcomes and can be measured in adults using plain films obtained in the "cochlear view." The objective of this study was to assess interrater and intrarater reliability of measuring depth of insertion using cochlear view radiography.

Study Design: Prospective, observational.

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COVID-19 is a rapidly growing global pandemic caused by a novel coronavirus. With no vaccine or definitive treatment, public health authorities have recommended a strategy of "social distancing," reducing individual interaction, canceling elective procedures, and limiting nonessential services. Health care providers must determine what procedures are considered "elective," balancing risk of treatment delays with that of coronavirus exposure to patient, family, and providers.

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Coronavirus disease 2019 (COVID-19) is a novel coronavirus resulting in high mortality in the adult population but low mortality in the pediatric population. The role children and adolescents play in COVID-19 transmission is unclear, and it is possible that healthy pediatric patients serve as a reservoir for the virus. This article serves as a summary of a single pediatric institution's response to COVID-19 with the goal of protecting both patients and health care providers while providing ongoing care to critically ill patients who require urgent interventions.

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Exposure to aminoglycoside antibiotics can lead to the generation of toxic levels of reactive oxygen species (ROS) within mechanosensory hair cells of the inner ear that have been implicated in hearing and balance disorders. Better understanding of the origin of aminoglycoside-induced ROS could focus the development of therapies aimed at preventing this event. In this work, we used the zebrafish lateral line system to monitor the dynamic behavior of mitochondrial and cytoplasmic oxidation occurring within the same dying hair cell following exposure to aminoglycosides.

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Neuregulin-1 (NRG1) ligand and its epidermal growth factor receptor (EGFR)/ERBB family regulate normal cellular proliferation and differentiation in many tissues including the cochlea. Aberrant NRG1 and ERBB signaling cause significant hearing impairment in mice. Dysregulation of the same signaling pathway in humans is involved in certain types of cancers such as breast cancer or non-small cell lung cancer (NSCLC).

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Hypothesis: The zebrafish lateral line can be used to identify small molecules that protect against cisplatin-induced hair cell death.

Background: Cisplatin is a commonly used chemotherapeutic agent, which causes hearing loss by damaging hair cells of the inner ear. There are currently no FDA-approved pharmacologic strategies for preventing this side effect.

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Objectives/hypothesis: Small, powerful magnets are increasingly available in toys and other products, and are responsible for increasing numbers of foreign body injuries in children. Small, spherical, neodymium magnets available since 2008 are of particular concern. We aimed to identify all cases of upper aerodigestive foreign bodies at our institution over 15.

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Cisplatin, one of the most commonly used anticancer drugs, is known to cause inner ear hair cell damage and hearing loss. Despite much investigation into mechanisms of cisplatin-induced hair cell death, little is known about the mechanism whereby cisplatin is selectively toxic to hair cells. Using hair cells of the zebrafish lateral line, we found that chemical inhibition of mechanotransduction with quinine and EGTA protected against cisplatin-induced hair cell death.

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Hypothesis: The "in-bone" method of culturing utricles described here is a reliable and atraumatic technique for culturing mature mouse hair cells and studying hair cell death and protection.

Background: The current in vitro technique for studying hair cells of the mature mouse utricle involves removal from the temporal bone and free floating culture in media. This technique can be problematic because of variability in the preservation of the sensory epithelium and a steep learning curve that results in injury of the sensory epithelium in less experienced hands.

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We have previously published results from a screen of 1,040 FDA-approved drugs and bioactives (NINDS Custom Collection) for drugs that protect against neomycin-induced hair cell death (Ou et al., J Assoc Res Otolaryngol 10:191-203, 2009). Further evaluation of this drug library identified eight protective drugs that shared a common quinoline scaffold.

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Inner ear hair cell loss is the most common pathology seen after ototoxic drug injury. While certain drugs such as aminoglycosides and cisplatin are well-known to have dramatic ototoxic effects, it is probable that there are other drugs that cause occult degrees of hair cell loss and lesser degrees of hearing loss. Anti-cancer drugs are particularly strong candidates due to their general cytotoxicity.

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Several animal models have been used for the study of mechanosensory hair cells and hearing loss. Because of the difficulty of tissue acquisition and large animal size, these traditional models are impractical for high-throughput screening. The zebrafish has emerged as a powerful animal model for screening drugs that cause and prevent hair cell death.

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Objective: To study routine culture-negative persistent cervical lymphadenitis in children treated surgically during a 10-year period (December 26, 1997, to October 1, 2007) at a single institution.

Design: Retrospective case series.

Setting: Tertiary university-based pediatric referral center.

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The hair cells of the larval zebrafish lateral line provide a useful preparation in which to study hair cell death and to screen for genes and small molecules that modulate hair cell toxicity. We recently reported preliminary results from screening a small-molecule library for compounds that inhibit aminoglycoside-induced hair cell death. To potentially reduce the time required for development of drugs and drug combinations that can be clinically useful, we screened a library of 1,040 FDA-approved drugs and bioactive compounds (NINDS Custom Collection II).

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The zebrafish is a valuable model for studying hair cell development, structure, genetics, and behavior. Zebrafish and other aquatic vertebrates have hair cells on their body surface organized into a sensory system called the lateral line. These hair cells are highly accessible and easily visualized using fluorescent dyes.

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We have used time-lapse imaging to study cisplatin-induced hair cell death in lateral line neuromasts of zebrafish larvae in vivo. We found that cisplatin-induced hair cell death occurred much more slowly than had been shown to occur in aminoglycoside-induced hair cell death. By prelabeling hair cells with FM1-43FX, and assessing hair cell damage, it was established that cisplatin causes hair cell loss in the lateral line in a dose-dependent fashion.

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