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Biomedical subjects

Lawrence R Lustig

Publications and source records attributed to Lawrence R Lustig.

15 recordsLinked to original sources
PubMed2006

Progressive deafness and altered cochlear innervation in knock-out mice lacking prosaposin.

After a yeast two-hybrid screen identified prosaposin as a potential interacting protein with the nicotinic acetylcholine receptor (nAChR) subunit alpha10, studies were performed to characterize prosaposin in the normal rodent inner ear. Prosaposin demonstrates diffuse organ of Corti expression at birth, with gradual localization to the inner hair cells (IHCs) and its supporting cells, inner pillar cells, and synaptic region of the outer hair cells (OHCs) and Deiters' cells (DCs) by postnatal day 21 (P21). Microdissected OHC and DC quantitative reverse transcriptase-PCR and immunohistology localizes prosaposin mRNA to DCs and OHCs, and protein predominantly to the apex of the DCs. Subsequent studies in a prosaposin knock-out (KO) (-/-) mouse showed intact but slightly reduced hearing through P19, but deafness by P25 and reduced distortion product otoacoustic emissions from P15 onward. Beginning at P12, the prosaposin KO mice showed histologic organ of Corti changes including cellular hypertrophy in the region of the IHC and greater epithelial ridge, a loss of OHCs from cochlear apex, and vacuolization of OHCs. Immunofluorescence revealed exuberant overgrowth of auditory afferent neurites in the region of the IHCs and proliferation of auditory efferent neurites in the region of the tunnel of Corti. IHC recordings from these KO mice showed normal I-V curves and responses to applied acetylcholine. Together, these results suggest that prosaposin helps maintain normal innervation patterns to the organ of Corti. Furthermore, prosaposin's overlapping developmental expression pattern and binding capacity toward the nAChR alpha10 suggest that alpha10 may also play a role in this function.

Acoustic Stimulation↗
PubMed2006

Nicotinic acetylcholine receptor structure and function in the efferent auditory system.

This article reviews and presents new data regarding the nicotinic acetylcholine receptor subunits alpha9 and alpha10. Although phylogentically ancient, these subunits have only recently been identified as critical components of the efferent auditory system and medial olivocochlear pathway. This pathway is important in auditory processing by modulating outer hair cell function to broadly tune the cochlea and improve signal detection in noise. Pharmacologic properties of the functionally expressed alpha9alpha10 receptor closely resemble the cholinergic response of outer hair cells. Molecular, immunohistochemical, and knockout mice studies have added further weight to the role this receptor plays in mediating the efferent auditory response. Alternate and complementary mechanisms of outer hair cell efferent activity might also be mediated through the nAChR alpha9alpha10, either through secondary calcium stores, second messengers, or direct protein-protein interactions. We investigated protein-protein interactions using a yeast-two-hybrid screen of the nAChR alpha10 intracellular loop against a rat cochlear cDNA library. Among the identified proteins was prosaposin, a precursor of saposins, which have been shown to act as neurotrophic factors in culture, can bind to a putative G0-coupled cell surface receptor, and may be involved in the prevention of cell death. This study and review suggest that nAChR alpha9alpha10 may represent a potential therapeutic target for a variety of ear disorders, including preventing or treating noise-induced hearing loss, or such debilitating disorders as vertigo or tinnitus.

Animals↗
PubMed2006

Cochlear implantation in patients with neurofibromatosis type 2 and bilateral vestibular schwannoma.

OBJECTIVE: To investigate the results of cochlear implantation in patients with neurofibromatosis Type 2 (NF2) and bilateral vestibular schwannoma. STUDY DESIGN: Retrospective case review. SETTING: Three academic tertiary referral centers. PATIENTS: Seven patients with NF2 and bilateral vestibular schwannoma who lost hearing in at least one ear after treatment of their tumor (surgery or radiation therapy). INTERVENTION: Cochlear implantation after treatment of their vestibular schwannoma. MAIN OUTCOME MEASURE: Postimplantation audiometric scores (pure-tone average thresholds, consonant-nucleus-consonant (CNC) words/phonemes, Central Institute for the Deaf (CID) sentences, Hearing in Noise Test (HINT) quiet/noise, and Monosyllable, Trochee, Spondee (MTS) recognition/category tests), patient satisfaction, and device use patterns. RESULTS: The average age at implantation was 40 years (range, 16-57 yr). Follow-up ranged from 6 to 88 months after implantation. Three patients were implanted with residual useful hearing in the contralateral ear, whereas four patients had no hearing in the contralateral ear. Hearing loss was due to surgical excision of tumor (n=5) or gamma-knife radiotherapy (n=2). Postactivation pure-tone average thresholds in the implanted ear ranged from 30 to 55 dB (average, 32.5 dB), although speech reception testing varied considerably among subjects. Despite this variability, all patients continue to use the device on a daily basis. CONCLUSION: In selected cases of deafness in patients with NF2 where there has been anatomic preservation of the auditory nerve after acoustic neuroma resection or radiation therapy, cochlear implantation may offer some improvement in communication skills, including the possibility of open-set speech communication in some patients. These results compare favorably to the auditory brainstem implant offering an alternative for hearing rehabilitation in patients with NF2.

Adolescent↗
PubMed2005

Sir Charles Alfred Ballance: contributions to otology and neurotology.

STUDY DESIGN: A review of primary and secondary historical and scientific literature concerning the life and writings of Sir Charles Alfred Ballance (1856-1936). RESULTS: Sir Charles Alfred Ballance was a pioneer in otology and neurotology, responsible for many "firsts" in the field, including the complete removal of a cerebellopontine angle tumor with significant patient survival and grafting the mastoid cavity with epithelium to speed healing. He was a strict abdicator of the complete mastoid operation with ligature of the jugular vein and drainage of the lateral sinus, and he advanced many other neurotologic procedures during his lifetime. He successfully sectioned the VIIIth cranial nerve, relieving a patient from intractable vertigo, developed a meticulous system for treating the complications of suppurative infections of the mastoid, diligently studied facial nerve reanastomosis, and was the first to perform a spinal accessory to facial nerve anastomosis for the relief of facial palsy. Ballance published over 75 original articles and was the primary author on two landmark books concerning temporal bone and neurologic surgery. He was the leader of many surgical societies and maintained a life of research and science until his death. CONCLUSION: Sir Charles Ballance was a pioneer in neurotologic and skull base surgery and greatly advanced the field during its inception. This work focuses on the otologic and neurotologic endeavors of Sir Charles Alfred Ballance, bringing his accomplishments into modern relief.

Ear Diseases↗
PubMed2004

Characterization of the human nicotinic acetylcholine receptor subunit alpha (alpha) 9 (CHRNA9) and alpha (alpha) 10 (CHRNA10) in lymphocytes.

Though the nicotinic acetylcholine receptor (nAChR) subunits alpha9 and alpha 10 have been thoroughly characterized within hair cells of the organ of Corti in the inner ear, prior studies have shown that they are also expressed in lymphocytes. In this report, we sought to more definitively characterize the nAChR subunits alpha9 and alpha10 within various populations of human lymphocytes. Using a combination of techniques, including RT-PCR, single-cell RT-PCR, Northern and western blot analysis, and immunofluorescence, expression of both alpha9 and alpha 10 was demonstrated in purified populations of T-cells (CD3+, CD4+, CD8+ and the Jurkat, MT2 and CEM T-cell lines) and B-cells (CD19+, CD80+ and EBV-immortalized B-cells). Single-lymphocyte recording techniques failed to identify an ionic current in response to applied acetylcholine in either T-cells or B-cells. These results clearly demonstrate the presence of these nicotinic receptor subunits within several populations of human lymphocytes, implicating their role in the immune response. However, a lack of demonstrated response to applied acetylcholine using standard single-cell recording techniques suggests a physiology different than that seen in hair cells of the inner ear.

Acetylcholine↗
PubMed2004

GJB2 gene mutations in cochlear implant recipients: prevalence and impact on outcome.

OBJECTIVE: To determine the prevalence of GJB2 gene mutations in patients undergoing cochlear implantation (CI) and their impact on rehabilitative outcome following implantation. DESIGN: Prospective determination of GJB2 mutation by sequence analysis by denaturing high-performance liquid chromatography and its correlation with outcome following CI. SETTINGS: Two tertiary academic medical centers. PATIENTS: Subjects who have met the audiologic criteria and have undergone CI. RESULTS: Of 77 cochlear implant recipients screened, 13 (18%) harbored a detectable sequence alteration in the GJB2 gene. Only 3 of these 13 patients had hearing loss clearly attributable to a biallelic GJB2 mutation. There were 2 patients with homozygous mutations, including a 35delG and a 167delT mutation, and a third with a compound heterozygous mutation. Of the remaining 10 patients, 8 had 1 deafness allele, while 2 had a normal polymorphism that was not believed to be implicated in the hearing loss. Six patients had the common 35delG mutation: 5 patients had heterozygous mutations, which are probably not related to the underlying hearing loss (a second deafness allele cannot be ruled out in these cases because of the screening methodology used), while 1 patient had a homozygous mutation, which was clearly implicated in the patient's deafness. Rehabilitative outcome among those with detectable sequence alterations, as well as the 3 patients with biallelic mutations, varied but were similar on average when compared with outcomes seen in our entire CI population. CONCLUSIONS: A large percentage of implant candidates harbor mutations or sequence alterations in the GJB2 gene, although only a small number of these changes are biallelic and a clear cause of the hearing loss. These results demonstrate that patients with GJB2-related deafness clearly benefit from CI.

Adolescent↗
PubMed2004

The history of intratympanic drug therapy in otology.

The application of drugs through the eardrum and into the middle ear to treat various otologic disorders has recently gained wide-spread popularity. Despite the relatively recent interest in this technique, if one considers any application of medication into the middle ear as intratympanic therapy, the roots of this method can really be considered to date back to antiquity. This article presents the development of intratympanic drug therapy from early times through the nineteenth century.

Administration, Topical↗
PubMed2003

Paget's disease and fibrous dysplasia.

Paget's disease and fibrous dysplasia are benign disorders that can involve the temporal bone and skull base. They commonly lead to otolaryngologic symptoms such as impingement of cranial nerves or the orbit or blockage of the external auditory canal or paranasal sinuses, although they can often be a challenge to diagnose because of their insidious presentation. Their benign nature and common presentation within the difficult-to-access confines of the skull base should lead the clinician to exercise caution in their treatment, reserving surgical intervention for either diagnosis or the relief of symptoms. As a better understanding of the etiology of these conditions develops and new pharmacotherapeutic agents are tested, it is likely that physicians will be able to turn to medical rather than surgical techniques to treat these disorders.

Ethmoid Bone↗
PubMed2003

Current digital imaging for the otolaryngologist.

Digital imaging has arrived as a standard tool for the otolaryngologist. There is no better evidence of this than the American Academy of Otolaryngology-Head and Neck Surgery moving to an all-digital format for its 2003 national meeting. No longer will 35-mm slide projectors be available for any presentations in the country's largest otolaryngology program. Also, all of the major journals in the field now accept or require digital files of illustrations and photographs. With this change in standard, the question is no longer if, or even when to incorporate digital imaging techniques, but how to do so most efficiently. This can be quite a challenge, given the ever-changing field of computer technology. This article is intended to introduce the fundamentals of digital imaging, and how this technology can best be integrated into an otolaryngology practice.

Computers↗
PubMed2003

Comparison of the bone anchored hearing aid implantable hearing device with contralateral routing of offside signal amplification in the rehabilitation of unilateral deafness.

OBJECTIVE: Monaural hearing imposes constraints under many listening conditions. The authors compared the effects of a semi-implantable bone conductor, the Entific bone anchored hearing aid, with conventional contralateral routing of offside signal amplification to assess rehabilitative benefit in adults with unilateral deafness. DESIGN: Prospective trials of subjects with unilateral deafness using benefit surveys, source identification testing, and hearing in noise testing. SETTING: Tertiary referral center, outpatient surgical and audiologic services. PATIENTS: Adults with unilateral deafness (pure tone average >90 dB, SD <20%) after acoustic neuroma excision (n = 7), meningitis (n = 1), sudden sensorineural hearing loss (n = 1), and sudden sensorineural hearing loss with chronic suppurative otitis media (n = 1). Entry criteria included normal hearing in the contralateral ear (pure tone average <25 dB, SD >80%). INTERVENTION: Subjects were fitted with contralateral routing of offside signal amplification devices for 1 month and tested with contralateral routing of offside signal before mastoid implantation of the deaf ear, fitting, and testing for bone anchored hearing aid. OUTCOME MEASURES: Subjects' assessment of experience with their devices and patterns of use, 2) source azimuth identification in noise test, and 3) speech discrimination in quiet and in noise under conditions of noise-front, noise-to-normal-ear, and noise-to-deaf-ear. RESULTS: There was consistent satisfaction with bone anchored hearing aid implantation and amplification, and poor acceptance of contralateral routing of offside signal amplification. Sound localization was poor at baseline and with both bone anchored hearing aid and contralateral routing of offside signal. Relative to baseline, contralateral routing of offside signal and bone anchored hearing aid produced significantly better speech recognition in noise under most conditions. The bone anchored hearing aid enabled significantly better speech recognition than contralateral routing of offside signal in quiet and in a composite of noise conditions. The advantages may relate to averting the interference of speech signals delivered to the better ear, as occurs with conventional contralateral routing of offside signal amplification. CONCLUSIONS: Preliminary data in subjects with normal monaural hearing indicate that vibromechanical stimulation with the bone anchored hearing aid overcomes some of the negative head shadow effects in unilateral deafness. The bone anchored hearing aid system, when placed on the side of a deaf ear, yields greater benefit in subjects with normal monaural hearing than does contralateral routing of offside signal amplification. It seems that this rehabilitative approach can expand the sound field of monaural listeners in further enhancing speech understanding. Observations suggest that further understanding of bone conduction as implemented in transcranial stimulation will guide further options for patients with monaural hearing. Longer follow-up will help to determine whether communicative skill improvements with the bone anchored hearing aid outweigh the disadvantages of implantation surgery, costs, and device maintenance.

Adult↗
PubMed2003

Dehiscence of bone overlying the superior canal as a cause of apparent conductive hearing loss.

OBJECTIVE: To identify patients with superior semicircular canal dehiscence and apparent conductive hearing loss and to define the cause of the air-bone gap. STUDY DESIGN: Prospective study of patients with superior canal dehiscence. SETTING Tertiary referral center. PATIENTS: Vestibular and/or auditory findings indicative of canal dehiscence and demonstration of superior canal dehiscence on computed tomography of the temporal bone. INTERVENTION: Vestibular-evoked myogenic potentials, three-dimensional eye movement recordings, and surgical resurfacing of the superior canal. OUTCOME MEASURE: Association of superior canal dehiscence with an air-bone gap on audiometry. RESULTS: Four patients with dehiscence of bone overlying the superior canal were found to have air-bone gaps in the affected ears that were greatest at lower frequencies and averaged 24 +/- 7 dB over the frequency range of 250 to 4,000 Hz. Three of these patients had undergone stapedectomy before the identification of superior canal dehiscence. The air-bone gap was unchanged postoperatively. Each patient had an intact vestibular-evoked myogenic potential (VEMP) response from the affected ear, a finding that would not have been expected based on a middle ear cause of conductive hearing loss. One patient underwent resurfacing of the superior canal through a middle fossa approach. Postoperatively, his vestibular symptoms were relieved, and his air conduction thresholds were improved by 20 dB. CONCLUSIONS: Superior canal dehiscence can result in apparent conductive hearing loss. The third mobile window created by the dehiscent superior canal results in dissipation of acoustic energy and is a cause of inner ear conductive hearing loss.

Adult↗
PubMed2003

Cochlear implantation in patients with bilateral Ménière's syndrome.

OBJECTIVE: To evaluate the indications and clinical outcomes (audiologic and vestibular) in patients with Ménière's syndrome who have undergone cochlear implantation. STUDY DESIGN: This is a retrospective review of patients at a large tertiary academic medical center. PATIENTS: Nine patients were included in the study with AAO-HNS criteria for diagnosis of Ménière's syndrome as well as bilateral severe to profound sensorineural hearing loss as an indication for undergoing cochlear implantation. Audiologic criteria for implantation were considered in the context of speech recognition performance with well-fit, powerful hearing aids noting large fluctuations in performance levels in some patients. In all cases, the poorer hearing ear was implanted. Seven subjects had bilateral disease and had progressed to profound sensorineural hearing loss. The average age of the patients was 61 years. Six patients had undergone previous surgery to control vertigo, including endolymphatic shunt surgery and vestibular nerve section. No patient had received previous treatment with intra-tympanic gentamicin. Symptoms of Ménière's syndrome had been present in all patients for at least 10 years before implantation. INTERVENTION: Cochlear Implantation. MAIN OUTCOME MEASURES: Pre- and Postoperative audiometric scores (monosyllable words/phonemes, Central Institute for the Deaf (CID) sentences, Hearing in Noise Test (HINT) in quite/noise (+10 db)), pre- and postoperative vestibular symptoms (number of vestibular attacks, aural fullness, tinnitus). RESULTS: Follow-up after implantation ranged from 1 to 5 years. Average 6 month postimplantation scores were: monosyllable words/phonemes = 52%/65%, CID sentences = 82%, HINT in quiet/noise = 70%/50%. Average 1-year postimplant scores were: monosyllable words/phonemes = 60%/76%, CID sentences = 97%, HINT in quiet/noise = 89%/78%. Postoperative speech recognition scores were, on average, substantially greater than preoperative scores. While there were few complications associated with implantation, some patients experienced alterations in their implant performance in association with fluctuations in vestibular symptoms. CONCLUSIONS: Patients with advanced binaural involvement with Ménière's Disease may present a challenge to conventional criteria for cochlear implant candidacy because of fluctuating symptoms. We observed significant benefit over baseline in a consecutive series of patients with Ménière's syndrome who progressed to bilateral, severe-to-profound sensorineural hearing loss and underwent cochlear implantation. Further, previous vestibular surgery, including labyrinthectomy, does not contraindicate cochlear implantation.

Adult↗
PubMed2002

Otolaryngologic aspects of the Lewis & Clark Expedition, 1803-1806.

Medical difficulties related to otolaryngology that occurred during the Lewis & Clark Expedition (1803-1806) are highlighted. These difficulties included ear and face frostbite, upper respiratory infections, temporal vessel laceration from an air gun accident, neck scrofula, and a pediatric neck mass. The custom of Clatsop Indian head flattening is also described. These descriptions also aim to illustrate the state of otolaryngology during the early 19th century in America.

Child↗