Charles G. Wright

The mouse Ames waltzer hearing-loss mutant is caused by mutation of Pcdh15 , a novel protocadherin gene

The neuroepithelia of the inner ear contain hair cells that function as mechanoreceptors to transduce sound and motion signals. Mutations affecting these neuroepithelia cause deafness and vestibular dysfuction in humans. Ames waltzer (av) is a recessive mutation found in mice that causes deafness and a balance disorder associated with the degeneration of inner ear neuroepithelia. Here we report that the gene that harbours the av mutation encodes a novel protocadherin. Cochlear hair cells in the av mutants show abnormal stereocilia by 10 days after birth (P10). This is the first evidence for the requirement of a protocadherin for normal function of the mammalian inner ear.

Cochlear implant electrode insertion: the round window revisited.

Objective: To examine aspects of round window (RW) anatomy that are relevant to its use as a portal for atraumatic insertion of cochlear implant electrodes.

Inner ear histopathology in patients treated with Cis-Platinum.†‡

Temporal bone histopathology was studied in five patients (aged 51–67) who received cis‐diamminedichloroplatinum (DDP) chemotherapy for head and neck squamous cell carcinoma. In each case, a sensorineural hearing loss occurred during the course of treatment and temporal bones were acquired 3–5 hours postmortem for anatomical study.

Surgical Aspects of Cochlear Implantation: Mechanisms of Insertional Trauma

The development of hybrid electroacoustic devices has made conservation of residual hearing an important goal in cochlear implant surgery. Our laboratory has recently conducted anatomical studies directed toward better understanding mechanisms underlying loss of residual hearing associated with electrode insertion. This paper provides an overview of observations based on microdissection, scanning electron microscopy and temporal bone histology relating to inner ear injury that may occur during implant surgery. Trauma to cochlear structures including lateral wall tissues, the basilar membrane, the osseous spiral lamina and the modiolus is considered in relation to the implications of specific types of injury for hearing preservation. These findings are relevant to the design of future implant devices and to various important issues regarding the surgical technique used for implantation, including the possible use of the round window as a portal of entry for electrode insertion.

Ototoxicity of otic drops applied to the middle ear in the chinchilla

Previous studies have shown that the application of topical otic drops to the external ear canals of animals with patent tympanostomy tubes may result in hearing impairment and cochlear hair cell loss. Otic drops are used in patients with tympanostomy tubes or tympanic membrane perforations and could have deleterious effects on the human membranous labyrinth. This report describes the inner ear damage that occurred after direct application of aminoglycoside-containing otic drops to the middle ears of experimental animals. The membranous labyrinths of 25 chinchillas were studied two days to five months after application of Cortisporin otic suspension (which contains neomycin, polymyxin B, hydrocortisone, and propylene glycol) to the middle ear cavity. Application of 0.5 ml of Cortisporin resulted in degeneration of all inner and outer hair cells throughout the cochlea, as well as severe damage to the stria vascularis. Moderate to severe degeneration of the vestibular receptor organs was also observed. The endolymphatic sacs showed dark-staining endolymph, cellular debris, and macrophages in the sac lumina, as well as increased activity of the epithelial lining.

Auditory and temporal bone abnormalities in charge association

CHARGE association is a recently described cluster of congenital defects including ocular coloboma, heart disease, choanal atresia, retarded development and/or CNS abnormalities, genital hypoplasia, and ear anomalies. Although congenital hearing loss has been reported in CHARGE association, no information regarding the underlying temporal bone disease is available in the literature to date. The authors evaluated four patients with multiple anomalies consistent with CHARGE syndrome. Two surviving patients have bilateral severe hearing loss on auditory brain stem response testing. Two patients did not survive, and their temporal bones were obtained at autopsy for histologic examination. All four temporal bones showed severe middle ear defects including ossicular deformities, absence of the stapedius muscle, absence of the oval window, aberrant course of the facial nerve, and dehiscence of the facial nerve canal. In the more severely affected case, a Mondini-type malformation of the cochlea was present, together with multiple anomalies of the vestibular apparatus. Vestibular defects also occurred in the other case; however, the cochleae were found to be normally developed.

Tympanostomy tubes and otic drops

Otic drops have been proposed as a form of prophylaxis against the otitis media which follows middle ear contamination by water in patients with tympanostomy tubes. The potential adverse effects of this form of therapy were studied in chinchillas with tympanostomy tubes; 31 chinchillas underwent bilateral tympanostomy tube insertion. Seven animals had a mixture of green dye and Cortisporinotic suspension placed in both external auditory canals 24 hours following the placement of tympanostomy tubes and were sacrificed 30 minutes later for gross examination; 3 of these animals had previous eustachian tube obstruction with Silastic sponge. Twenty‐one animals had Cortisporinotic suspension placed in the right external auditory canal on postoperative days 3, 4, 5, 6 and 7. No otic drops were placed in the left ear. Ten of these 20 animals had VIIIth nerve action potentials measured on postoperative day 17 and the other 11 animals had VIIIth nerve action potentials measured on postoperative day 42 followed by immediate sacrifice for histological examination and scanning electronmicroscopy. The remaining 3 animals had VIIIth nerve action potentials measured 21 days following tympanostomy tube insertion and served as electrophysiological controls.

Middle ear cholesteatoma: An animal model

Topical otic preparations now in clinical use contain a variety of antibiotics and solvents that may produce severe inflammation if they reach the middle ear cavity. This report describes the response of the chinchilla middle ear to direct application of one such preparation that appears to act as a nonspecific irritant. Cortisporin otic suspension (containing neomycin, polymyxin B, hydrocortisone, and propylene glycol) was introduced into the bullae of 32 chinchillas that were kept alive for four days to five months before histologic examination of their temporal bones. All the experimental animals had tissue damage and inflammation within the middle ear. The changes observed included proliferation of ciliated and secretory columnar cells, formation of granulation tissue, bone erosion, and osteoneogenesis. Some areas of the mucosa underwent metaplasia to stratified squamous epithelium; this metaplastic epithelium, however, did not produce keratin. In the majority of animals kept for two months or more, cholesteatoma was identified in the middle ear. The cholesteatomas appeared to develop as a result of penetration of external canal epidermis through intact tympanic membranes or as the result of migration of epidermis through perforations. The experimental cholesteatomas behaved like those seen clinically in humans, with extensive erosion of bony structures within the middle ear.

Cis‐platinum vestibular toxicity

Cis‐diamminedichloroplatinum has been proven to be an effective neoplastic agent. Nephrotoxicity and ototoxicity are two prominent side effects of this drug. Investigation of ototoxicity has been limited to auditory function. This report details the first known case of vestibular toxicity following platinum therapy. In addition, a prospective vestibular testing program is reported. Cancer 47:857–8589, 1981.

Neuroepithelial defects of the inner ear in a new allele of the mouse mutation Ames waltzer

This report presents new findings regarding a recessive insertional mutation in the transgenic line TgN2742Rpw that causes deafness and circling behavior in mice homozygous for the mutation. The mutant locus was mapped to a region on mouse chromosome 10 close to three spontaneous recessive mutations causing deafness: Ames waltzer (av), Waltzer (v), and Jackson circler (jc). Complementation testing revealed that the TgN2742Rpw mutation is allelic with av. Histological and auditory brainstem response (ABR) evaluation of animals that have the new allele balanced with the av(J) allele (called compound heterozygotes, TgN2742Rpw/av(J)) supports our genetic analysis. ABR evaluation shows complete absence of auditory response throughout the life span of TgN2742Rpw/av(J) compound heterozygotes. Scanning electron microscopy revealed abnormalities of inner and outer hair cell stereocilia in the cochleae of TgN2742Rpw mutants at 10 days after birth (DAB). The organ of Corti subsequently undergoes degeneration, leading to nearly complete loss of the cochlear neuroepithelium in older mutants by about 50 DAB. The vestibular neuroepithelia remain morphologically normal until at least 30 DAB. However, by 50 days, degenerative changes are evident in the saccular macula, which progresses to total loss of the saccular neuroepithelium in older animals. The new allele of av reported here will be designated av(TgN2742Rpw).