Recent advances in otitis media. 3. Animal models; anatomy and pathology; pathogenesis; cell biology and genetics.
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Animals↗
Biomedical subjects
Saumil N Merchant
Publications and source records attributed to Saumil N Merchant.
Mechanisms of hearing loss resulting from middle-ear fluid.
Fluid in the middle ear, a defining feature of otitis media with effusion (OME), is commonly associated with a 20- to 30-dB conductive hearing loss. The effects and relative importance of various mechanisms leading to conductive hearing loss were investigated in a human temporal bone preparation. Umbo velocity in response to ear-canal sound was measured with a laser vibrometer while saline and silicone fluids of viscosity 5-12,000 cSt were introduced into the middle ear to contact part or all of the tympanic membrane (TM) and fill part or all of the middle ear. At low frequencies, reductions in umbo velocity (deltaVU) of up to 25 dB depended on the percentage of the original middle-ear air space that remained air-filled, which suggests that the primary mechanism in hearing loss at low frequencies is a reduction of the admittance of the middle-ear air space due to displacement of air with fluid. At higher frequencies, deltaVU (of up to 35 dB) depended on the percentage of the TM contacted by fluid, which suggests that the primary mechanism at high frequencies is an increase in tympanic membrane mass by entrained fluid. The viscosity of the fluid had no significant effect on umbo velocity. deltaVU for the fluid-filled middle ear matched hearing losses reported in patients whose middle ear was believed to be completely filled with fluid. The difference between deltaVU for a partly-filled middle ear and hearing losses reported in patients whose middle ear was believed to be incompletely fluid-filled is consistent with the reported effect of middle-ear underpressure (commonly seen in OME) on umbo velocity. Small amounts of air in the middle ear are sufficient to facilitate umbo motion at low frequencies.
Aged↗
A normative study of tympanic membrane motion in humans using a laser Doppler vibrometer (LDV).
Laser Doppler vibrometry was used to measure the sound-induced tympanic membrane (TM) velocity, assessed near the umbo, in 56 normal hearing human subjects at nine sound frequencies. A second series of measurements was made in 47 subjects with sensorineural hearing loss (SNHL). Each set of measurements has features in common with previously published results. The measured velocity magnitude (normalized by the stimulus sound pressure) at any one frequency ranged among subjects by factors of 3-0.3 (+/-10 dB) from the mean and the phase angle of the normalized velocity ranged from +/-15 degrees around the mean at low frequencies to more than +/-200 degrees around the mean at 6 kHz. Measurements repeated after intervals of minutes to months were generally within 40% in magnitude (+/-3 dB) and 20 degrees in phase. Sources of variability included the effect of small differences in the location of the measurement on the TM and small static middle-ear pressures. No effects of stimulus level, ear sidedness (right or left), gender, age or the presence or absence of SNHL were found. These results provide a baseline normal response for studies of TM velocity with conductive hearing losses of different etiologies.
Acoustic Stimulation↗
Temporal bone histopathology in alport syndrome.
OBJECTIVE: To determine the histopathologic abnormalities within the cochlea in Alport syndrome. BACKGROUND: Alport syndrome, which manifests as hereditary nephritis and sensorineural hearing loss (SNHL), is caused by mutations in genes that code for the proportional, variant3, proportional, variant4, and proportional, variant5 chains of type IV collagen. The proportional, variant3, proportional, variant4, and proportional, variant5 chains of type IV collagen are present in the basement membrane of the organ of Corti. Previous temporal bone studies have failed to identify histopathologic correlates for the SNHL. METHODS: We examined temporal bones from nine individuals with a clinical diagnosis of Alport syndrome. One of our cases also had genetic testing that showed a mutation in the type IV collagen proportional, variant5 chain gene. RESULTS: By light microscopy, eight of nine cases demonstrated two unique pathologic changes: 1) a "zone of separation" between the basilar membrane and overlying cells of the organ of Corti and 2) presence of cells filling the tunnel of Corti and extracellular spaces of Nuel. The cytologic losses of hair cells, stria vascularis, and cochlear neuronal cells were insufficient to account for the observed SNHL in our cases. Electron microscopy was performed in four cases; all four demonstrated the following: 1) the zone of separation that was observed at light microscopy occurred between the basement membrane and the basilar membrane, 2) the cells within the tunnel of Corti and spaces of Nuel were morphologically similar to supporting cells, and 3) the basement membrane of strial capillaries and the spiral vessel (under the basilar membrane) were normal. CONCLUSIONS: The histopathologic correlates of cochlear involvement in Alport syndrome are abnormalities of the basement membrane of cells of the organ of Corti and dysmorphogenesis (cellular infilling of the tunnel and extracellular spaces) of the organ of Corti. We hypothesize that these abnormalities result in SNHL by altering cochlear micromechanics.
Adolescent↗
Axial mesodermal dysplasia sequence: autopsy findings.
We describe an infant with the phenotype of the "axial mesodermal dysplasia spectrum" who had the oculo-auriculo-vertebral sequence and caudal dysgenesis. Postmortem studies identified anomalies of the middle ear ossicles, and muscles, in association with microtia and atresia of the external auditory canals, but no cerebral abnormalities.
Abnormalities, Multiple↗
Superior semicircular canal dehiscence presenting as conductive hearing loss without vertigo.
OBJECTIVE: The objective of this study was to describe superior semicircular canal dehiscence (SSCD) presenting as otherwise unexplained conductive hearing loss without vestibular symptoms. STUDY DESIGN: Retrospective. SETTING: Tertiary referral center. PATIENTS: The study comprised 8 patients (10 ears), 5 males and 5 females aged 27 to 59 years. All 10 ears had SSCD on high-resolution computed tomography scan of the temporal bone. DIAGNOSTIC TESTS AND RESULTS: All 10 ears had significant conductive hearing loss. The air-bone gaps were largest in the lower frequencies at 250, 500, and 1000 Hz; the mean gaps for these 3 frequencies for the 10 ears were 49, 37, and 35 dB, respectively. Bone-conduction thresholds below 2000 Hz were negative (-5 dB to -15 dB) at one or more frequencies in 8 of the 10 ears. There were no middle ear abnormalities to explain the air-bone gaps in these 10 ears. Computed tomography scan and laboratory testing indicated lack of middle ear pathology; acoustic reflexes were present, vestibular evoked myogenic potentials (VEMPs) were present with abnormally low thresholds, and umbo velocity measured by laser Doppler vibrometry was above mean normal. Middle ear exploration was negative in six ears; of these six, stapedectomy had been performed in three ears and ossiculoplasty in two ears, but the air-bone gap was unchanged postoperatively. The data are consistent with the hypothesis that the SSCD introduced a third mobile window into the inner ear, which in turn produced the conductive hearing loss by 1) shunting air-conducted sound away from the cochlea, thus elevating air-conduction thresholds; and 2) increasing the difference in impedance between the oval and round windows, thus improving thresholds for bone-conducted sound. CONCLUSION: SSCD can present with a conductive hearing loss that mimics otosclerosis and could explain some cases of persistent conductive hearing loss after uneventful stapedectomy. Audiometric testing with attention to absolute bone-conduction thresholds, acoustic reflex testing, VEMP testing, laser vibrometry of the umbo, and computed tomograph scanning can help to identify patients with SSCD presenting with conductive hearing loss without vertigo.
Acoustic Impedance Tests↗
Clinical, experimental, and theoretical investigations of the effect of superior semicircular canal dehiscence on hearing mechanisms.
HYPOTHESIS: A superior semicircular canal dehiscence affects hearing by introducing a third window into the inner ear that 1) lowers cochlear input impedance, 2) shunts air-conducted sound away from the cochlea resulting in conductive hearing loss, and 3) improves bone-conduction thresholds by increasing the difference in impedance between the vestibule and the round window. BACKGROUND: Superior semicircular canal dehiscence has been linked to a "conductive" hearing loss characterized by a decrease in the sensitivity to air-conducted sound and hypersensitivity to bone-conducted sound. METHODS: Four investigations were performed: 1) laser-Doppler vibrometer measurements of sound-induced umbo velocity in patients with computed tomographic scan-confirmed superior semicircular canal dehiscence; 2) laser-Doppler vibrometry of sound-induced motions of the vestibular lymph (either perilymph or endolymph) exposed in a chinchilla model of superior semicircular canal dehiscence; 3) studies in chinchillas of the effect of superior semicircular canal dehiscence on the cochlea's sensitivity to bone-conducted sounds; and 4) anatomically based theoretical analyses of sound flow through the human cochlea and semicircular canals. RESULTS: The low-frequency umbo velocity in superior semicircular canal dehiscence patients without previous middle ear surgery ranged from normal through high normal. This tendency toward hypermobility suggests a decrease in cochlear impedance. Measurements of sound-induced velocity of the lymph within a superior semicircular canal dehiscence in chinchillas demonstrated sound flow through the dehiscence. Measurements of the cochlear potential demonstrated a superior semicircular canal dehiscence-induced increase in response to bone-conducted sound in eight of nine chinchillas. An anatomically based model of the human ear predicts changes in auditory sensitivity similar to audiometric changes in superior semicircular canal dehiscence. CONCLUSION: The results suggest that superior semicircular canal dehiscence can affect hearing function by introducing a third window into the inner ear.
Animals↗
Transverse fracture of the temporal bone.
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Accidental Falls↗
Postauricular periosteal-pericranial flap for mastoid obliteration and canal wall down tympanomastoidectomy.
OBJECTIVE: To describe an effective technique for mastoid cavity obliteration in canal wall down tympanomastoidectomy for chronic otitis media and review its efficacy in producing a dry, low-maintenance, small mastoid cavity. DESIGN: : Retrospective clinical study of a consecutive series of procedures from 1995 to 2000. SETTING: Tertiary referral center and institutional academic practice in otology and neurotology. PATIENTS: Sixty consecutive procedures for active chronic otitis media with a minimum follow-up of 12 months (mean, 31 mo; range, 12-80 mo). INTERVENTION: All patients had canal wall down mastoidectomy with simultaneous tympanoplasty including split-thickness skin grafting. An inferiorly pedicled, periosteal-pericranial flap was used in conjunction with autologous bone pate to obliterate the mastoid cavity. The additional length provided by the pericranial extension of the flap permitted it to reach superior to the lateral canal and into the sinodural angle, with improved coverage of bone pate and better reduction of cavity size. OUTCOME MEASURES: The primary outcome measure was control of suppuration and creation of a dry, low-maintenance mastoid cavity, which was assessed using a previously developed semiquantitative scale. This scale includes a temporal dimension to assess control of infection. Secondary outcome measures included postoperative complications (i.e., hematoma, infection, flap necrosis, and meatal stenosis) and incidence of recurrent or residual cholesteatoma. RESULTS: Forty-nine ears (82%) maintained a small, dry, healthy mastoid cavity. Five ears (8%) had intermittent otorrhea easily controlled by topical treatment. Six ears (10%) had suboptimal control of otorrhea, of which four had meatal stenosis. There were no residual or recurrent cholesteatomas. Outcomes remained stable over progressively longer follow-up, up to 80 months. CONCLUSION: Obliteration of a canal wall down mastoid cavity by a postauricular periosteal-pericranial flap with autologous bone pate is a reliable and effective technique that results in a dry, trouble-free mastoid cavity in 90% of patients with active chronic otitis media.
Adolescent↗
Association between osteoporosis and otosclerosis in women.
Similarities between osteoporosis and otosclerosis have been noted, including a similar association with the COL1A1 gene. Herein, the authors explore the possible clinical relationship between these two common disorders of bone. In this retrospective study, the medical charts of 100 women aged 50 through 75 years who had undergone stapedectomy for otosclerosis were reviewed and the prevalence of osteoporosis in these women was noted. Similarly, the prevalence of osteoporosis was determined in a control group of 100 women aged 50 to 75 years with presbycusis. Fifteen of 100 women with otosclerosis had a concomitant diagnosis of osteoporosis as compared with four of 100 women with presbycusis, yielding a significant clinical association (p = 0.007) between otosclerosis and osteoporosis. This study suggests an association between otosclerosis and osteoporosis, providing impetus and justification for future prospective clinical studies and related research.
Age Distribution↗
Temporal bone histopathological and quantitative analysis of mitochondrial DNA in MELAS.
OBJECTIVES/HYPOTHESIS: Although hearing loss is common in MELAS (syndrome of mitochondrial encephalopathy, lactic acidosis and stroke-like episodes), the histopathology of the temporal bone has not been reported. The majority of cases of MELAS are linked to a mitochondrial DNA (mtDNA) mutation at nucleotide 3243. In MELAS, normal mtDNA and mutant mtDNA coexist in a heteroplasmic manner. The purpose of the study was to report the otopathological findings from two patients with MELAS and quantitative mtDNA analysis in the inner ear of one of these patients. STUDY DESIGN: Basic scientific histopathological examination and quantitative mtDNA analysis of the temporal bone. METHODS: Temporal bones were embedded in celloidin and sectioned for light microscopic study. Graphic reconstruction of the cochlea was performed using the method described by Schuknecht. For quantitative mtDNA analysis, total DNA from the membranous part of the inner ear was collected, amplified by polymerase chain reaction, and digested with the restriction enzyme. The percentage of mutant/total mtDNA was measured by the ratio of fluorescence intensity. RESULTS: Histopathological examination revealed severe degeneration of the stria vascularis and degenerative change of spiral ganglion cells in both patients. The quantitative DNA studies showed that the proportion of mutant to wild-type mtDNA was similar in both histologically affected and histologically unaffected tissues within the inner ear. CONCLUSION: Dysfunction of the stria vascularis and spiral ganglion cells causes sensorineural hearing loss in MELAS.
Adult↗
Diagnostic utility of laser-Doppler vibrometry in conductive hearing loss with normal tympanic membrane.
HYPOTHESIS: It was hypothesized that laser-Doppler vibrometry measurements of umbo velocity in aerated middle ears with conductive loss can differentiate ossicular interruptions, stapes fixations, and mallear fixations. More generally, we hypothesize that laser-Doppler vibrometry measurements of umbo velocity can give information about how differences in the impedance that the ossicles work against affect middle-ear function. BACKGROUND: Laser-Doppler vibrometry is a well-established research tool for exploring middle-ear function. The authors wished to investigate its potential as a clinical tool for differential diagnosis of the cause of conductive hearing loss. METHODS: Laser-Doppler vibrometry was used to investigate the relationship between the sound-induced velocity of the tympanic membrane at the umbo and the cause of conductive hearing loss when the tympanic membrane was normal and the middle ear was aerated. The results of measurements in 17 adult ears before exploratory tympanotomy were compared with the surgically determined cause of the hearing loss. The authors also measured the motion of the umbo in 10 patients who had undergone successful small-fenestra stapedectomy procedures. In all the studied ears, pure-tone audiograms were measured at the time of laser-Doppler vibrometry testing. RESULTS: There were clear statistical differences between the umbo velocity in normal ears and in ears with different ossicular pathologic conditions. There was also a clear separation of the results between ears with ossicular interruptions and ossicular fixation. The pattern of laser-Doppler vibrometry measurements in poststapedectomy ears approximated the pattern in ears with ossicular interruptions. CONCLUSION: Comparison of laser-Doppler vibrometry results and audiometry may be a sensitive and selective indicator of ossicular pathologic conditions as well as a useful tool for investigating middle ear function.
Audiometry, Pure-Tone↗
Middle-ear mechanics of Type III tympanoplasty (stapes columella): I. Experimental studies.
OBJECTIVE: To investigate the mechanics of Type III tympanoplasty by developing a cadaveric temporal bone model. BACKGROUND: Type III stapes columella tympanoplasty involves the placement of a tympanic membrane graft, usually made of temporalis fascia, directly onto the stapes head. The procedure is usually done in conjunction with a canal wall down mastoidectomy. Postoperative hearing results vary widely, with air-bone gaps of 10 to 60 dB. The structural features responsible for the wide range in hearing results have not been systematically investigated. METHODS: Canal wall down Type III procedures were performed in eight cadaveric temporal bones. Acoustic stimuli were presented in the ear canal, and round window velocity VRW (used as an index of hearing) was measured, while systematically varying stapes mobility, mechanical properties of tympanic membrane graft, and tightness of connection between tympanic membrane graft and stapes. The effect of interposing a thin cartilage disc between the tympanic membrane graft and stapes head was also assessed. RESULTS: When the middle ear was aerated and the stapes was mobile, VRW was 15 to 30 dB lower than in an intact, normal ear. Stapes fixation led to a significant reduction in VRW; reduction was greatest at low frequencies. There was little effect of varying the tightness of connection between the tympanic membrane graft and stapes head. Sound energy was transmitted from the graft to the stapes as long as the graft was in physical contact with the stapes head. Different tympanic membrane graft materials with a range of mechanical properties (stiffness and mass) resulted in little variation in VRW. Interposing a thin cartilage disc between the tympanic membrane graft and stapes improved VRW in the lower frequencies by 5 to 10 dB. The authors hypothesize that the disc acted to increase the effective vibrating area of the graft. CONCLUSIONS: The feasibility of using a cadaveric temporal bone model to study the mechanics of Type III tympanoplasty was demonstrated. A mobile stapes and aerated middle ear were essential for a successful Type III tympanoplasty. There was little effect of varying the mechanical properties of the tympanic membrane graft or changing the tightness of connection between the graft and stapes head. Improved results were achieved by interposing a thin cartilage disc between the graft and stapes head to increase the effective vibrating area of the graft.
Aged↗
Middle ear mechanics of Type III tympanoplasty (stapes columella): II. Clinical studies.
OBJECTIVES: To determine the structural features that are responsible for the large variation in postoperative hearing results after Type III stapes columella tympanoplasty, to compare the clinical results after Type III tympanoplasty with predictions based on experimental investigations using a temporal bone model, and to investigate the effectiveness of a modification in surgical technique for Type III reconstruction. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. INCLUSION CRITERIA: The ear was healed with an intact tympanic membrane graft; the status of the stapes was known, whether mobile or fixed; and the postoperative status of aeration of the middle ear was known, whether aerated or not. MAIN OUTCOME MEASURE: Air-bone gap at frequencies 250, 500, 1,000, 2,000 and 4,000 Hz. RESULTS: In ears with temporalis fascia graft onto stapes head: mobile stapes and aerated middle ear (n = 34), mean air-bone gaps at audiometric frequencies were 15 to 30 dB, consistent with predictions of the experimental model; mobile stapes and nonaerated middle ear (n = 16), large air-bone gaps of 35 to 55 dB; fixed stapes and aerated middle ear (n = 4), large air-bone gaps of 30 to 50 dB; fixed stapes and nonaerated middle ear (n = 2), large air-bone gaps of 30 to 70 dB. In ears with a fascia-cartilage graft onto stapes head, where a thin disc of meatal cartilage, 0.3 to 0.5 mm thick and 4 to 6 mm in diameter was interposed between the fascia graft and the stapes head: mobile stapes and aerated middle ear (n = 9), mean air-bone gaps at audiometric frequencies were 10 to 25 dB, about 5 dB better at 250, 500, and 2,000 Hz than in ears with only a fascia graft ( <0.05), improvement consistent with that observed experimentally when a thin cartilage disc was used in the temporal bone model, hypothesis that the cartilage increased the effective vibrating area of the graft; mobile stapes and nonaerated middle ear (n = 2), air-bone gaps were 40 to 50 dB. CONCLUSIONS: Large air-bone gaps of 30 to 70 dB occurred as a result of stapes fixation, nonaeration of the middle ear, or both. When the stapes was mobile and the middle ear was aerated, a fascia graft resulted in air-bone gaps of 15 to 30 dB. Interposing a thin disc of cartilage between the fascia graft and stapes head to improve the effective vibrating graft area gave better hearing, with air-bone gaps of 10 to 25 dB. The clinical Type III results were consistent with predictions based on experimental investigations of mechanics of the Type III procedure in a temporal bone model.
Acoustic Impedance Tests↗
Erythromycin ototoxicity.
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Anti-Bacterial Agents↗
Deoxyribonucleic acid contamination in archival human temporal bones: a potentially significant problem.
HYPOTHESIS: Contamination of archival human temporal bones with extraneous deoxyribonucleic acid may represent a potentially significant problem in the analysis of nucleic acids isolated from archival specimens. BACKGROUND: During the past decade, there has been growing interest in the development of molecular biologic techniques that can be applied to the investigation of pathologic changes in archival human temporal bones. The impetus for the development of these techniques is in part related to the fact that the temporal bone collections represent a repository of archival material compiled over decades, which is not available from living patients. METHODS: An archival human temporal bone specimen from a male patient with the Mohr-Tranebjaerg syndrome (formerly called DFN-1) and a well-characterized mutation was analyzed for the presence of the mutation by a standard method for extraction, isolation, amplification, and sequencing of deoxyribonucleic acid. The experiment was repeated four times. RESULTS: The deoxyribonucleic acid sequence from three of four extractions was normal. The known mutation was easily and repeatedly demonstrated in a blood sample from the same individual. Because Mohr-Tranebjaerg syndrome is X-linked, there is only one allele, and therefore there is no potential endogenous source to account for the normal sequence that was amplified. Contamination of the tissue sections by extraneous deoxyribonucleic acid presumably occurred during acquisition and processing of the temporal bone. CONCLUSIONS: Contamination of archival temporal bones with exogenous deoxyribonucleic acid is a significant potential problem that must be considered in the interpretation of the results of deoxyribonucleic acid retrieved from archival sections. The authors recommend collecting blood samples from temporal bone donors in the future to ensure the availability of a reliable source of deoxyribonucleic acid.
Aged↗
Efficient method for the proteomic analysis of fixed and embedded tissues.
Formalin-fixed and paraffin-embedded (FFPE) tissues present a particular challenge for proteomic analysis. Yet, most of the archived tissues in hospitals and tissue banks worldwide are only available in this form. We have developed conditions for removal of the embedding medium and protein digestion, such that informative tryptic peptides are released from fixed proteins which are suitable for analysis by liquid chromatography-mass spectrometry (LC-MS). We demonstrate that the peptide identifications made by this approach compare favorably to those made from matched fresh frozen tissue. Moreover, we demonstrate that a high level of sequence coverage can be observed for proteins of interest.
Amino Acid Sequence↗