Biomedical subjects

S N Merchant

Publications and source records attributed to S N Merchant.

At least 37 records · Page 2Linked to original sources

PubMed2000

Temporal bone studies of the human peripheral vestibular system. Aminoglycoside ototoxicity.

Quantitative assessments of vestibular hair cells and Scarpa's ganglion cells were performed on 17 temporal bones from 10 individuals who had well-documented clinical evidence of aminoglycoside ototoxicity (streptomycin, kanamycin, and neomycin). Assessment of vestibular hair cells was performed by Nomarski (differential interference contrast) microscopy. Hair cell counts were expressed as densities (number of cells per 0.01 mm2 surface area of the sensory epithelium). The results were compared with age-matched normal data. Streptomycin caused a significant loss of both type I and type II hair cells in all 5 vestibular sense organs. In comparing the ototoxic effect on type I versus type II hair cells, there was greater type I hair cell loss for all 3 cristae, but not for the maculae. The vestibular ototoxic effects of kanamycin appeared to be similar to those of streptomycin, but the small sample size precluded definitive conclusions from being made. Neomycin did not cause loss of vestibular hair cells. Within the limits of this study (maximum postototoxicity survival time of 12 months), there was no significant loss of Scarpa's ganglion cells for any of the 3 drugs. The findings have implications in several clinical areas, including the correlation of vestibular test results to pathological findings, the rehabilitation of patients with vestibular ototoxicity, the use of aminoglycosides to treat Meniere's disease, and the development of a vestibular prosthesis.

Adult↗

PubMed2000

Temporal bone studies of the human peripheral vestibular system. Meniere's disease.

Quantitative assessments of vestibular hair cells and Scarpa's ganglion cells were performed on temporal bones from 24 patients with well-documented Meniere's disease. Of these, 18 had unilateral disease and 6 had bilateral disease. Vestibular hair cell counts were made in each of the 5 sense organs by Nomarski (differential interference contrast) microscopy. Hair cell counts were expressed as densities: number of cells per 0.01 mm2 surface area of the sensory epithelium. The results were compared with age- and sex-matched normal data. The type I hair cell densities for all vestibular sense organs were within the range for normative data. On the other hand, there was a significant loss (p < .01) of type II hair cells for all 3 cristae and both maculae. There was also a significant loss of Scarpa's ganglion cells (p < .001) when compared with normative data. The findings indicate a selective loss of type II hair cells and Scarpa's ganglion cells in Meniere's disease. These new observations have implications regarding the pathophysiological mechanism and clinical manifestations of Meniere's disease.

Adult↗

PubMed1999

Prevention of hearing loss in experimental pneumococcal meningitis by administration of dexamethasone and ketorolac.

Pneumococcal meningitis remains a significant cause of morbidity, particularly sensorineural hearing loss. Recent literature has suggested that a vigorous host immune response to Streptococcus [corrected] pneumoniae is responsible for much of the neurologic sequelae, including deafness, after bacterial meningitis. This study used a rabbit model of hearing loss in experimental pneumococcal meningitis to evaluate the therapeutic effect of two anti-inflammatory agents, dexamethasone and ketorolac, coadministered with ampicillin. Both adjunctive drugs minimized or prevented sensorineural hearing loss compared with placebo. Dexamethasone, administered 10 min before ampicillin, was particularly effective in minimizing mean hearing threshold change compared with placebo for both clicks (dexamethasone: 6.7-dB sound pressure level [SPL] vs. placebo: 33. 4-dB SPL, P=.0078) and 10-kHz tone bursts (dexamethasone: 8.4-dB SPL vs. placebo: 53.4-dB SPL, P=.0003). These findings support the beneficial role of anti-inflammatory agents in reducing the incidence of hearing loss from pneumococcal meningitis, especially if therapy is instituted early in the course of infection.

Acoustic Stimulation↗

PubMed1999

A method for quantitative assessment of vestibular otopathology.

BACKGROUND: Quantitative studies of the vestibular system using serial sections from human temporal bones have been limited because it has been generally difficult to reliably differentiate hair cells from supporting cells and type I from type II hair cells. OBJECTIVES: 1. To develop a new method to overcome the above limitations and permit quantitative assessments of types I and II vestibular hair cells in archival temporal bone sections. 2. To demonstrate that this method is reliable, valid, and repeatable. 3. To describe the advantages of this method compared with other traditional techniques. 4. To discuss the potential of this method to provide new insight into the etiology, pathology, and pathophysiology of vestibular disorders. STUDY DESIGN: Examination of archival human temporal sections prepared for conventional light microscopy. METHODS: The method used Nomarski (differential interference contrast) microscopy to permit visualization of the cuticular plate and stereociliary bundle, to allow unambiguous identification of hair cells. Types I and II hair cells were distinguished by their morphological characteristics. The method was used to measure the density of types I and II hair cells in each vestibular sense organ. Raw-density counts were corrected for potential double counting using Abercrombie's formula. RESULTS: Intrarater and interrater reliability was strong as judged by high Pearson and Spearman correlation values (P < .01). Abercrombie's formula was shown to be valid by comparison with counts made by an unbiased calibration technique using the optical disector principle (correlation coefficients > 0.9, P < .01). CONCLUSIONS: The method described in this report has several advantages when compared with alternative techniques such as surface preparations. The method is applicable to archival bones, permits simultaneous evaluation of the rest of the labyrinth, is relatively inexpensive, and does not preclude other techniques of study (e.g., polymerase chain reaction and immunostaining). Case studies of temporal bones with aminoglycoside ototoxicity and Meniere's disease are used to show how this method has the potential to provide new insight into the pathology and pathophysiology of vestibular disorders.

Cell Count↗

PubMed1999

Does otosclerosis occur only in the temporal bone?

HYPOTHESIS: Otosclerosis does not occur outside the temporal bone. BACKGROUND: The widely accepted assumption that otosclerosis is confined to the temporal bone has never been tested. It is important to investigate this issue, particularly because of evidence that otosclerosis may be a systemic (genetic) disease that could affect other bones. METHODS: Biopsies from 9 to 11 skeletal sites were obtained from 2 patients with clinical otosclerosis. Two hundred forty-one nontemporal bone sections were examined by light microscopy. RESULTS: No nontemporal skeletal bone section showed histologic evidence of otosclerosis. The data indicate, with 95% confidence, that the true prevalence of otosclerosis in the extratemporal skeleton of the 2 patients examined was < 3%. CONCLUSIONS: These findings suggest that otosclerosis is unlikely to occur outside the temporal bone. Factors unique to the otic capsule that may predispose it to otosclerosis are lack of bone remodeling and the presence of globuli interossei.

Adult↗

PubMed1998

Current status and future challenges of tympanoplasty.

Four decades after the introduction of tympanoplasty, the goal of achieving stable and long-term hearing improvement after tympanoplasty surgery for chronic otitis media continues to be elusive. In this review, we focus on the current status of our understanding of the mechanics and pathology of the middle ear after tympanoplasty surgery. We also analyze some problems and challenges faced by clinicians and basic scientists in the quest for improved postoperative hearing results.

Chronic Disease↗

PubMed1998

Acoustic mechanisms: canal wall-up versus canal wall-down mastoidectomy.

The contribution of the middle ear air spaces to sound transmission through the middle ear in canal wall-up and canal wall-down mastoidectomy was studied in human temporal bones by measurements of middle ear input impedance and sound pressure difference across the tympanic membrane for the frequency range 50 Hz to 5 kHz. These measurements indicate that, relative to canal wall-up procedures, canal wall-down mastoidectomy results in a 1 to 5 dB decrease in middle ear sound transmission below 1 kHz, a 0 to 10 dB increase between 1 and 3 kHz, and no change above 3 kHz. These results are consistent with those reported by Gyo et al. (Arch Otolaryngol Head Neck Surg 1986;112:1262-8), in which umbo displacement was used as a measure of sound transmission. A model analysis suggests that the reduction in sound transmission below 1 kHz can be explained by the smaller middle ear air space volume associated with the canal wall-down procedure. We conclude that as long as the middle ear air space is aerated and has a volume greater than 0.7 ml, canal wall-down mastoidectomy should generally cause less than 10 dB changes in middle ear sound transmission relative to the canal wall-up procedure.

Acoustic Impedance Tests↗

PubMed1998

Toynbee Memorial Lecture 1997. Middle ear mechanics in normal, diseased and reconstructed ears.

A review of the structure-function relationships in normal, diseased and reconstructed middle ears is presented. Variables used to describe the system are sound pressure, volume velocity and acoustic impedance. We discuss the following: (1) Sound can be transmitted from the ear canal to the cochlea via two mechanisms: the tympanoossicular system (ossicular coupling) and direct acoustic stimulation of the oval and round windows (acoustic coupling). In the normal ear, middle-ear pressure gain, which is the result of ossicular coupling, is frequency-dependent and smaller than generally believed. Acoustic coupling is negligibly small in normal ears, but can play a significant role in some diseased and reconstructed ears. (2) The severity of conductive hearing loss due to middle-ear disease or after tympanoplasty surgery can be predicted by the degree to which ossicular coupling, acoustic coupling, and stapes-cochlear input impedance are compromised. Such analyses are used to explain the air-bone gaps associated with lesions such as ossicular interruption, ossicular fixation and tympanic membrane perforation. (3) With type IV and V tympanoplasty, hearing is determined solely by acoustic coupling. A quantitative analysis of structure-function relationships can both explain the wide range of observed post-operative hearing results and suggest surgical guidelines in order to optimize the post-operative results. (4) In tympanoplasty types I, II and III, the hearing result depends on the efficacy of the reconstructed tympanic membrane, the efficacy of the reconstructed ossicular chain and adequacy of middle-ear aeration. Currently, our knowledge of the mechanics of these three factors is incomplete. The mechanics of mastoidectomy and stapedectomy are also discussed.

Biomechanical Phenomena↗

PubMed1998

Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction.

DFNA9 is an autosomal dominant, nonsyndromic, progressive sensorineural hearing loss with vestibular pathology. Here we report three missense mutations in human COCH (previously described as Coch5b2), a novel cochlear gene, in three unrelated kindreds with DFNA9. All three residues mutated in DFNA9 are conserved in mouse and chicken Coch, and are found in a region containing four conserved cysteines with homology to a domain in factor C, a lipopolysaccharide-binding coagulation factor in Limulus polyphemus. COCH message, found at high levels in human cochlear and vestibular organs, occurs in the chicken inner ear in the regions of the auditory and vestibular nerve fibres, the neural and abneural limbs adjacent to the cochlear sensory epithelium and the stroma of the crista ampullaris of the vestibular labyrinth. These areas correspond to human inner ear structures which show histopathological findings of acidophilic ground substance in DFNA9 patients.

Amino Acid Sequence↗

PubMed1998

Correlations between pathologic changes in the stapes and conductive hearing loss in otosclerosis.

The goal of this temporal bone study was to quantify the relationship between specific histologic changes at the stapes footplate and the magnitude of the air-bone gap in otosclerosis. The study material comprised 26 specimens with otosclerosis and 37 age-matched controls. Detailed anatomic measurements were made on each histologic section through the stapes footplate in each bone, resulting in 30 different measurement parameters for each bone. For frequencies 250 to 2,000 Hz, the conductive hearing loss correlated highly with (p < .01) and appeared to be caused primarily by narrowing and loss of the annular ligament, especially at the posterior stapediovestibular joint space. The size of the air-bone gap appeared to be determined by the extent and degree of this pathologic change. Schuknecht's hypothesis that bony ankylosis of the footplate would be associated with an air-bone gap of >30 dB was supported by our data. However, the degree and extent of bony footplate ankylosis could not be reliably predicted by the size of the air-bone gap.

Aged↗

PubMed1997

Anatomy of the normal human cochlear aqueduct with functional implications.

There is great variation in published descriptions of the shape, size, and patency of the human cochlear aqueduct. The first part of this paper describes the anatomy of the normal human cochlear aqueduct as determined from a study of 101 temporal bones. Nineteen bones aged 0-1 years and approximately 10 bones per decade of life until age 100 years were examined. The aqueduct was found to have a funnel shaped aperture at the cranial end with a dural sheath extending into it for a varying distance. The rest of the aqueduct was filled with a meshwork of loose connective tissue, often with a central lumen within it. Four types of patencies were noted: central lumen patent throughout length of aqueduct (34%), lumen filled with loose connective tissue (59%), lumen occluded by bone (4%), and obliteration of the aqueduct (3%). The mean value (+/- SD) of the narrowest portion was 138 (+/- 58) microns which occurred 200-300 microns from the cochlear end of the aqueduct. There was no correlation between age and narrowest diameter, or between age and category of patency. In the second part of this paper, we propose quantitative models of aqueduct function, based on measurements of ductal dimensions and known acoustical properties of the inner ear. Our model analyses suggest that in normal ears, the aqueduct (1) cannot support fluid flows large enough to explain stapedectomy gushers, (2) does filter out cardiac- and respiration-induced pulses in CSF and prevents them from affecting cochlear function, and (3) has little effect on normal ossicular transmission of sound for frequencies above 20 Hz. In pathological ears, such as those with ossicular disruption or after a type IV tympanoplasty, a patent aqueduct might affect hearing for frequencies below 150 Hz.

Acoustics↗

PubMed1997

Efficacy of tympanomastoid surgery for control of infection in active chronic otitis media.

The efficacy of surgery in controlling infection in 272 tympanomastoidectomy procedures for chronic otitis media (COM) was assessed by means of a four-point rating scale that incorporated both symptoms and signs, such as the presence or absence of otorrhea and granulation tissue. Of the 272 procedures, 170 were performed for COM with cholesteatoma and 102 were for active COM with granulation tissue but no cholesteatoma. Forty-seven percent were primary procedures, and 53% were revisions. Minimum follow-up was 12 months for all cases, with a mean of 30 months. Adequate control of infection occurred in 248 (91%) of the 272 cases. Of the 24 cases (9%) that developed persistent infection, 10 were controlled with a combination of oral and topical antibiotics and/or delayed skin grafting in the office. Thus overall satisfactory control of infection was achieved in 258 of 272 cases (95%). The outcome was influenced by the diagnostic category of COM: COM with cholesteatoma did significantly better than COM with granulation tissue (P = 0.02). The outcome was not influenced by the following variables: primary versus revision surgery, canal wall-up versus canal wall-down surgery, and extent of disease. The results suggest that active COM with granulation tissue may be more difficult to control than COM with cholesteatoma.

Administration, Oral↗

PubMed1997

Mechanics of type IV tympanoplasty: experimental findings and surgical implications.

In a type IV tympanoplasty, the stapes footplate is directly exposed to incoming sound while the round window is "shielded," usually with a fascia graft. Postoperative hearing results are quite variable, with air-bone gaps ranging from 10 to 60 dB. A cadaveric human temporal bone preparation was developed to investigate the middle ear mechanics of this operation to identify causes of variable results and to test predictions of a recently described theoretic model of type IV tympanoplasty. The ear canal, tympanic membrane, malleus, and incus were removed so as to expose the stapes and round window to the sound stimulus. A "cavum minor" chamber (air space adjacent to the round window) was constructed around the round window niche. The round window could be isolated from sound by placing an acoustic shield over this chamber. The mechanical properties of the shield, cavum minor, annular ligament, and round window membrane were varied experimentally. Stapes velocity as determined by an optical motion sensor was used as a measure of hearing level. The largest stapes velocity occurred with a mobile stapes and round window, a stiff shield, and a well-aerated cavum minor. Partial fixation of the stapes or round window caused a decrease in stapes velocity. Acoustic shields of conchal cartilage or Silastic silicone rubber sheeting (approximately 1 mm thick) provided near-optimal shielding. A temporalis fascia shield resulted in a stapes velocity 10 to 20 dB less than that seen with a cartilage or Silastic silicone rubber shield at low frequencies. A cavum minor air space as small as 16 microL was sufficient for unrestricted stapes motion, provided the air was in contact with the round window membrane. These results qualitatively matched predictions of our model, but there were some quantitative differences. The clinical implications of our results are that in order to optimize postoperative hearing, the surgeon should 1) preserve normal stapes mobility, preferably by covering the footplate with a very thin split-thickness skin graft, not a fascia graft; 2) reinforce a fascia shield with cartilage or Silastic silicone rubber; 3) create conditions that promote aeration of the round window niche; and 4) preserve the mobility of the round window membrane.

Adult↗

PubMed1997

Histopathology of labyrinthine fistulae in chronic otitis media with clinical implications.

The objective of this study was to describe the light microscopic pathology of labyrinthine fistulae in chronic otitis media (COM) in seven temporal bones and to discuss clinical and surgical implications. In COM, labyrinthine fistulae are usually caused by cholesteatoma, with the lateral semicircular canal being the most commonly affected site. Some fistulae are asymptomatic, whereas, others affect the auditory and vestibular systems to varying degrees. Surgical removal of cholesteatoma matrix over a fistula carries a risk of sensorineural hearing loss. Knowledge of the pathology of fistulae may provide a better understanding of their clinical manifestations and may allow a more rational approach to surgical management. The Massachusetts Eye and Ear Infirmary temporal bone collection contains 115 specimens with COM, of which seven specimens show pathologic fistulization of the bony labyrinth. Histologic sections from these seven bones were evaluated with respect to type of COM, location and size of fistula, changes in the inner ear adjacent to the fistula, middle ear and mastoid disease, and pathology in the vestibular and cochlear sense organs. The following conclusions are presented (a) Labyrinthine fistulae can be caused not only by cholesteatoma, but also by granulomatous COM without cholesteatoma and even by localized infection within a canal-down mastoid cavity. (b) Cholesteatoma matrix or inflammatory tissue usually becomes apposed to the endosteum or membranous labyrinth within the fistula. In most cases, reactive inner ear changes do not occur at the fistula site. Occasionally, there is thickening of the endosteum or chronic localized labyrinthitis. (c) Most bones do not show any alterations of the vestibular and cochlear sense organs. Occasionally, there is serous labyrinthitis, which might lead to partial sensorineural hearing loss. (d) A protective "walling-off" phenomenon in the labyrinth is not common. Therefore, if overwhelming infection or surgical trauma breaches the natural barriers of the endosteum/membranous labyrinth, then the fistula may allow rapid dissemination of infection throughout the inner ear.

Adolescent↗

PubMed1997

Analysis of middle ear mechanics and application to diseased and reconstructed ears.

OBJECTIVE: To review current concepts of the mechanical processes of the human middle ear, and to apply them to practical issues in clinical otology and tympanoplasty surgery. BACKGROUND: The wide range of conductive hearing losses associated with middle ear pathology and reconstruction cannot be adequately explained by simple models of middle ear function. METHODS: Variables used to describe the system are sound pressure, volume velocity, and acoustic impedance. The relationship between specific middle ear structures and these variables is described such that inferences can be drawn regarding sound conduction in the normal, diseased, and reconstructed middle ear. RESULTS AND CONCLUSIONS: Sound can be transmitted from the car canal to the cochlea via two mechanisms: the tympano-ossicular system (ossicular coupling) and direct acoustic stimulation of the oval and round windows (acoustic coupling). Acoustic coupling is negligibly small in normal ears, but can play a significant role in some diseased and reconstructed ears. In the normal ear, middle ear pressure gain (which is the result of ossicular coupling) is frequency-dependent and less than generally believed. The severity of conductive hearing loss due to middle-ear disease or after tympanoplasty surgery can be predicted by the degree to which ossicular coupling, acoustic coupling, and stapescochlear input impedance are altered. Hearing after type IV and V tympanoplasty is determined solely by acoustic coupling. The difference in magnitude between the oval- and round-window pressures is more important than the difference in phase in determining cochlear input. In tympanoplasty types I, II, and III, adequate middle-ear and round-window aeration is necessary and the tympanic membrane-ossicular configuration may be less crucial.

Acoustics↗

PubMed1996

A gene for non-syndromic autosomal dominant progressive postlingual sensorineural hearing loss maps to chromosome 14q12-13.

We report a novel locus responsible for postlingual progressive sensorineural hearing loss (designated DFNA9) that maps to chromosome 14q12-13. A large kindred with autosomal dominant transmission of non-syndromic hearing loss was clinically studied. Hearing in affected individuals deteriorated at approximately 20 years of age and progressed to anacusis in the fifth decade. A random genome-wide search using polymorphic short tandem repeats demonstrated linkage with D14S121 (maximum two point LOD score = 6.19, theta = 0). Haplotype analysis of recombination events defined a 9 cM disease interval, between D14S252 and D14S49.

Adult↗

PubMed1996

A human temporal bone study of changes in the basilar membrane of the apical turn in endolymphatic hydrops.

We observed that some temporal bones with endolymphatic hydrops (EH) showed varying degrees of basalward displacement (towards the scala tympani) of the basilar membrane (BM) in the apical turn of the cochlea. In some, the BM was adherent to the bony wall of the scala tympani (i.e., the interscalar septum). Such mechanical distortion of the BM could conceivably alter cochlear mechanics and lead to sensorineural hearing loss. The results of a systematic evaluation of 234 temporal bones to characterize, quantify and determine the functional significance of this observation are presented. Four groups of bones were evaluated: normal (N = 78), presbycusis (N = 96), Ménière's disease (N = 23), and EH secondary to labyrinthitis (N = 37). The incidence of extreme displacement of the BM in the apical turn such that it adhered to the interscalar septum was 52% in Ménière's disease, 57% in EH secondary to labyrinthitis, 10% in presbycusis, and 1% in normals. These differences were significant and could not be explained on the basis of age, sex, postmortem time, or artifact of technique or processing. Displacement of the BM was not observed in other turns of the cochlea. Its pathogenesis is not known, but may be related to atrophy of the spiral ligament. It is likely that such BM displacement results in sensorineural hearing loss. However, our data and theoretical analyses both indicate that such a loss will be restricted to frequencies below 100 Hz and that this pathologic change alone is not likely to cause appreciable hearing loss at clinically tested frequencies of 250 HZ and higher. Hence, even though this pathologic finding is common in endolymphatic hydrops, it cannot explain the low-frequency hearing lost observed in Ménière's disease.

Adult↗

PubMed1996

A human temporal bone study of acute bacterial meningogenic labyrinthitis.

It is well established that sensorineural hearing loss (SNHL) is an important sequela of acute bacterial meningitis. Previous human temporal bone histopathologic studies have suggested that such hearing loss is due to labyrinthitis. This study involved a detailed and systematic evaluation of the auditory and vestibular end-organs in 41 human temporal bones from patients with acute bacterial meningitis, aimed at describing the spectrum of histopathologic changes within the labyrinth, ascertaining likely routes for spread of infection from the meninges to the inner ear, and comparing the data from humans with those described in a rabbit model of meningogenic labyrinthitis. Our study revealed the following: (a) Suppurative labyrinthitis occurred in 20 (49%) bones. Of these 20 bones, the cochlea was affected in all, whereas the vestibular organs were involved in 10. Eosinophilic staining of inner ear fluids without the presence of inflammatory cells (so-called "serous" labyrinthitis) occurred in 14 of the remaining 21 bones. This staining occurred primarily within the vestibular system. Its significance and pathogenesis remains unknown; (b) Sensory and neural structures of the inner ear appeared intact in the majority of specimens, including bones with suppurative labyrinthitis and those with eosinophilic staining of inner ear fluids. This finding raises the possibility of preventing or reversing SNHL by therapeutic intervention. Spiral ganglion cells were severely degenerated in 12% of bones, indicating a retrocochlear site of hearing loss in addition to the cochlea. This subset of patients may perform poorly after cochlear implantation; (c) It has been traditionally assumed that irreversible and permanent SNHL is caused by suppurative labyrinthitis, whereas reversible SNHL is caused by serous labyrinthitis. Our findings question the validity of these assumptions; (d) The data were consistent with the hypothesis that both the cochlear modiolus and cochlear aqueduct can serve as potential pathways for spread of infection from the meninges to the inner ear; (e) There were many similarities in the histopathology of the inner ear in humans when compared with the rabbit model of meningogenic labyrinthitis. A notable difference was that the cochlear aqueduct appeared to be the sole pathway for spread of infection in the rabbit, whereas in the human, both the modiolus and aqueduct were possible pathways.

Adolescent↗