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S N Merchant

Publications and source records attributed to S N Merchant.

At least 19 recordsLinked to original sources
PubMed2004

A decrease in effective diameter of rat mesenteric venules due to leukocyte margination after a bolus injection of pentoxifylline--digital image analysis of an intravital microscopic observation.

The ability of leukocytes to adhere to endothelial cells (EC) and then to migrate out of the blood stream into tissues enable them to perform their surveillance functions. Adhesion of leukocytes to EC is, however, only possible if the cells have marginated as a result of rheological interaction with other blood cells in flow. Using Pentoxifylline (PTX), a rheologically active drug, to manipulate this interaction, we have imaged and quantified this margination phenomenon in vivo. A system has been developing to perform this imaging via an intravital microscope connected to an image processing system. Albino rats were anesthetized and cannulated for intravenous bolus injection (0.5 ml) of PTX (1.25 mg/ml) through the femoral vein. A longitudinal incision exposed the mesentery, part of which was observed under microscope to visualize microcirculation. The image of interest was then stored on computer hard drive. Individual leukocyte velocities were determined before and after PTX infusion. The leukocytes, marginating and sticking after PTX infusion either remained attached, constituting the peripheral marginating leukocyte pool in the postcapillary venules, or detached with different step velocities. The reduction in effective venular diameters as a result of leukocyte margination was estimated to be 32-44%. These results demonstrate the biological importance of hemodynamic displacement leading to docking, adhesion, rolling and migration processes of leukocytes in blood.

Animals↗
PubMed2001

Histopathology and molecular genetics of hearing loss in the human.

Hearing loss is among the most common disabilities of man. It has been estimated that over 70 million individuals in the world are hearing impaired with pure tone averages greater than 55 dB. A genetic etiology is thought to be responsible for over half of early onset hearing loss and at least one third of late onset hearing loss. In this review, examples of the histopathology of the inner ear in known genetic syndromes in the human will be presented in order to provide a structural basis for understanding molecular mechanisms of development and maintenance in the inner ear, and to serve the essential function of validating the applicability of animal genetic models of hearing loss to the human condition.

Abnormalities, Multiple↗
PubMed2001

How do tympanic-membrane perforations affect human middle-ear sound transmission?

Although tympanic-membrane (TM) perforations are common sequelae of middle-ear disease, the hearing losses they cause have not been accurately determined, largely because additional pathological conditions occur in these ears. Our measurements of acoustic transmission before and after making controlled perforations in cadaver ears show that perforations cause frequency-dependent loss that: (1) is largest at low frequencies; (2) increases as perforation size increases; and (3) does not depend on perforation location. The dominant loss mechanism is the reduction in sound-pressure difference across the TM. Measurements of middle-ear air-space sound pressures show that transmission via direct acoustic stimulation of the oval and round windows is generally negligible. A quantitative model predicts the influence of middle-ear air-space volume on loss; with larger volumes, loss is smaller.

Ear, Middle↗
PubMed2001

Histologic studies of the posterior stapediovestibular joint in otosclerosis.

OBJECTIVE: To determine the prevalence of ankylosis or otosclerosis at the posterior stapediovestibular joint (SVJ) in temporal bones with otosclerosis, with special reference to stapes surgery. BACKGROUND: Long-term success of the laser stapedotomy minus prosthesis (STAMP) procedure, anterior crurotomy, and similar partial stapedectomy procedures depends on lack of ankylosis and lack of otosclerosis involving the posterior SVJ. Previous work has shown that the air-bone gap in otosclerosis correlates with narrowing and loss of the SVJ space. However, the prevalence and histologic features of otosclerotic involvement of the posterior SVJ space have not been well characterized. METHODS: Histologic assessment of serial sections through the oval window niche in 140 temporal bones with otosclerosis that had been sectioned in the axial plane (age range 20-95 years, mean 68). Bones with stapes mobilization or stapedectomy were excluded. RESULTS AND CONCLUSIONS: Two of 140 bones had otosclerosis exclusively at the posterior SVJ. Of the remaining 138 bones, all of which had otosclerosis at the anterior SVJ, 82 bones also had otosclerosis at the posterior joint. Of the 56 bones without otosclerosis of the posterior joint, there was bony ankylosis of the posterior joint in 3 bones. Thus, 53 bones (38%) had neither ankylosis nor otosclerosis involving the posterior joint, and they would be potentially suitable for a laser STAMP or a similar procedure. There was no correlation between otosclerosis at the posterior SVJ and age, sex, or duration of conductive hearing loss. Otosclerosis at the posterior joint in one ear was significantly associated with its presence at the posterior joint in the opposite ear (p = 0.01). The audiogram could not be used to reliably predict otosclerotic involvement of the posterior SVJ or the degree of footplate pathologic changes, such as ankylosis.

Adult↗
PubMed2001

Temporal bone histopathologic and genetic studies in Mohr-Tranebjaerg syndrome (DFN-1).

OBJECTIVE: To describe the temporal bone histopathologic and genetic abnormalities in a case of Mohr-Tranebjaerg syndrome. BACKGROUND: Mohr-Tranebjaezrg syndrome (DFN-1) is an X-linked, recessive, syndromic hearing loss, characterized by postlingual sensorineural hearing loss with onset in childhood, followed in adult life by progressive dystonia, spasticity, dysphagia, and optic atrophy. The syndrome is caused by mutations in the DDP (deafness/dystonia peptide) gene, which are thought to result in mitochondrial dysfunction with subsequent neurodegeneration. The temporal bone pathologic changes in this syndrome have not been reported. METHODS: Hearing loss developed in the patient at age 4, blindness at age 48, and dystonia at age 57. Genetic studies on peripheral blood showed a l51delT mutation in his DDP gene. He died at age 66. The right temporal bone was subjected to light microscopy and polymerase chain reaction-based analysis of the DDP gene sequence. RESULTS: There was near complete loss of spiral ganglion cells with loss of nearly all peripheral and central processes. Only 1,765 spiral ganglion cells remained (8.5% of mean normal for age). The organ of Corti (including hair cells), stria vascularis, and spiral ligament were preserved. There was also a severe loss of Scarpa's ganglion cells with preservation of vestibular hair cells. The population of geniculate and trigeminal ganglion cells appeared normal. Sequence analysis from temporal bone DNA showed the 15ldelT DDP gene mutation. CONCLUSION: Sensorineural hearing loss in Mohr-Tranebjaerg syndrome is the result of a postnatal, progressive, severe auditory neuropathy.

Child, Preschool↗
PubMed2001

Decreasing hair cell counts in aging humans.

Deterioration of balance with advancing age is a well-known fact of life. Some investigators have reported a 50% prevalence of dizziness in the elderly. Clinically, progressive dysequilibrium of aging presents as gradually worsening balance due to age-related decline in function of the peripheral vestibular system, central nervous system, vision, and musculoskeletal system. Vestibular function testing has shown clear evidence of age-related changes in peripheral and central sites. Histopathologic changes in the vestibular sensory organs include progressive hair cell degeneration, otoconial degeneration in the otolith organs, and decreasing number of Scarpa's ganglion neurons. Recently, a new quantitative method of assessing vestibular otopathology has been described, utilizing Nomarski differential interference contrast microscopy. This technique has been applied to 67 human temporal bones of individuals from birth to age 100 to create a normative database of total, type I, and type II hair cell counts as a function of age. Results show a highly significant continuous decrease in all counts from birth to age 100, best fit by a linear regression model. Type I hair cell counts in all three semicircular canal cristae decrease at a similar rate, significantly faster than the degeneration observed in type I hair cells of the maculae. Type II hair cell counts decline at the same rate for all 5 sensory epithelia. These normative data provide the basis for comparisons to hair cell counts made in temporal bones from subjects with known vestibular disorders. They also provide a basis for drawing correlations between vestibular function testing and vestibular otopathology.

Aged↗
PubMed2001

Middle-ear function with tympanic-membrane perforations. I. Measurements and mechanisms.

Sound transmission through ears with tympanic-membrane (TM) perforations is not well understood. Here, measurements on human-cadaver ears are reported that describe sound transmission through the middle ear with experimentally produced perforations, which range from 0.5 to 5.0 mm in diameter. Three response variables were measured with acoustic stimulation at the TM: stapes velocity, middle-ear cavity sound pressure, and acoustic impedance at the TM. The stapes-velocity measurements show that perforations cause frequency-dependent losses; at low frequencies losses are largest and increase as perforation size increases. Measurements of middle-ear cavity pressure coupled with the stapes-velocity measurements indicate that the dominant mechanism for loss with TM perforations is reduction in pressure difference across the TM; changes in TM-to-ossicular coupling generally contribute less than 5 dB to the loss. Measurements of middle-ear input impedance indicate that for low frequencies, the input impedance with a perforation approximates the impedance of the middle-ear cavity; as the perforation size increases, the similarity to the cavity's impedance extends to higher frequencies. The collection of results suggests that the effects of perforations can be represented by the path for air-volume flow from the ear canal to the middle-ear cavity. The quantitative description of perforation-induced losses may help clinicians determine, in an ear with a perforation, whether poor hearing results only from the perforation or whether other pathology should be expected.

Acoustic Stimulation↗
PubMed2001

Middle-ear function with tympanic-membrane perforations. II. A simple model.

A quantitative model of the human middle ear with a tympanic-membrane (TM) perforation is developed. The model is constrained by several types of acoustic measurements made on human cadaver ears, which indicate that perforation-induced changes in transmission result primarily from changes in driving pressure across the TM and that perforation-induced change in the structure of the TM and its coupling to the ossicles contributes a substantially smaller component. The model represents the effect of a perforation on the pressure difference across the TM by inclusion of a path for sound coupling through the perforation from the ear canal to the middle-ear cavity. The model implies that hearing loss with perforations depends primarily on three quantities: the perforation diameter, sound frequency, and the volume of air in the middle-ear cavity. For the conditions that produce the largest hearing loss (low frequency and large perforation), the model yields a simple dependence of loss on frequency, perforation diameter, and middle-ear cavity volume. Predictions from this model may be useful to clinicians in determining whether, in particular cases, hearing losses are explainable by the observed perforations or if additional pathology must be involved.

Deafness↗
PubMed2001

Otopathology in a case of type I Waardenburg's syndrome.

We report a case of type I Waardenburg's syndrome that provides insight into the etiopathogenesis of sensorineural hearing loss (SNHL) in this syndrome. The subject, a 76-year-old woman with type I Waardenburg's syndrome (dystopia canthorum, heterochromia irides, and white hair), had congenital low-frequency SNHL in her right ear only, which had remained relatively stable throughout her life. Blood leukocyte DNA studies revealed a PAX-3 mutation with a 1 base pair C-to-A substitution in exon 5 at base 602. Light microscopic studies of the right cochlea showed intact neurosensory structures in only the lower basal turn, with the remainder of the cochlea showing absence of melanocytes, absence of stria vascularis, missing hair cells, dysmorphogenesis of the tectorial membrane, and lack of peripheral processes of the spiral ganglion cells. There was pathological alteration of the vestibular dark cells with marked reduction of melanocytes associated with these dark cells. The left inner ear was normal, with a full complement of neurosensory structures, including melanocytes. Because the PAX-3 gene is involved in neural crest development and melanocytes migrate from the neural crest to the ear, the findings in this case are consistent with the hypothesis that defective melanocyte migration or defective melanocyte function results in defective development of the stria vascularis (and perhaps other structures of the ear), leading to SNHL.

Cochlea↗
PubMed2000

Neurotologic manifestations and treatment of multiple spontaneous tegmental defects.

OBJECTIVE: To describe the causes, histopathologic features, manifestations, and treatment of symptomatic multiple spontaneous tegmental defects. STUDY DESIGN: Retrospective review of three clinical cases and one temporal bone histopathology report. CLINICAL FEATURES: Varied, including spontaneous cerebrospinal fluid otorhinorrhea, conductive hearing loss, chronic headaches, pneumocephalus, extradural abscess, and meningitis. A notable common feature was multiple (8-15) tegmental defects, 1 to 6 millimeters in diameter. Three of the four cases also included associated dural defects and small meningoencephaloceles or arachnoid granulations. Imaging studies generally underestimated the number of defects. INTERVENTION AND OUTCOMES: Successful middle cranial fossa repair with temporalis fascia was accomplished in the three clinical cases. Extension of exposure anteriorly and medially was necessary. Closure of the defects with a bone graft or equivalent synthetic material was not always possible, given the anatomic and pathologic features. Our data suggest that there are both congenital and acquired causes of the tegmental dehiscences. CONCLUSIONS: Multiple tegmen defects constitute a special entity. Successful repair requires a middle fossa craniotomy with extended exposure.

Aged↗
PubMed2000

Acoustic responses of the human middle ear.

Measurements on human cadaver ears are reported that describe sound transmission through the middle ear. Four response variables were measured with acoustic stimulation at the tympanic membrane: stapes velocity, middle-ear cavity sound pressure, acoustic impedance at the tympanic membrane and acoustic impedance of the middle-ear cavity. Measurements of stapes velocity at different locations on the stapes suggest that stapes motion is predominantly 'piston-like', for frequencies up to at least 2000 Hz. The measurements are generally consistent with constraints of existing models. The measurements are used (1) to show how the cavity pressure and the impedance at the tympanic membrane are related, (2) to develop a measurement-based middle-ear cavity model, which shows that the middle-ear cavity has only small effects on the motion of the tympanic membrane and stapes in the normal ear, although it may play a more prominent role in pathological ears, and (3) to show that inter-ear variations in the impedance at the tympanic membrane and the stapes velocity are not well correlated.

Acoustic Impedance Tests↗
PubMed2000

Effect of freezing and thawing on stapes-cochlear input impedance in human temporal bones.

The use of thawed frozen temporal bones offers advantages over fresh bones in the study of middle-ear and inner-ear mechanical function. We show, however, that freezing and thawing can cause a reduction in the magnitude of the input impedance of the stapes and cochlea Z(SC) in unfixed temporal bones from human cadavers of as much as a factor of 3-10 over the frequency range 25 Hz-7 kHz. Z(SC) is considered to be the sum of the impedances of the annular ligament Z(S) and the cochlea Z(C) and has been shown to be controlled by Z(S) below 1 kHz and by Z(C) at higher frequencies [Merchant et al., 1996. Hear. Res. 97, 30-45]. Experiments in which the inner ear was opened, drained, and refilled identified two mechanisms by which freezing and thawing can cause a reduction in the magnitude of Z(SC) (/Z(SC)/). Freezing can allow air to enter the inner ear, with the result that /Z(C)/ is reduced above about 1 kHz; and freezing can reduce /Z(S)/ which causes a reduction in /Z(SC)/ below 1 kHz. Changes in the phase angle of Z(SC) induced by freezing were small and were consistent with changes in /Z(SC)/. Removing air from the inner ear returned Z(C) to near its value in fresh bones, but /Z(SC)/ remained lower in some thawed bones by a factor of 2-3. Investigations of middle-ear function for which Z(SC) is critical should use fresh temporal bones only or should allow for the possible reduction in /Z(SC)/ in thawed frozen bones.

Aged↗
PubMed2000

Middle ear pathology can affect the ear-canal sound pressure generated by audiologic earphones.

OBJECTIVE: To determine how the ear-canal sound pressures generated by earphones differ between normal and pathologic middle ears. DESIGN: Measurements of ear-canal sound pressures generated by the Etymtic Research ER-3A insert earphone in normal ears (N = 12) were compared with the pressures generated in abnormal ears with mastoidectomy bowls (N = 15), tympanostomy tubes (N = 5), and tympanic-membrane perforations (N = 5). Similar measurements were made with the Telephonics TDH-49 supra-aural earphone in normal ears (N = 10) and abnormal ears with mastoidectomy bowls (N = 10), tympanostomy tubes (N = 4), and tympanic-membrane perforations (N = 5). RESULTS: With the insert earphone, the sound pressures generated in the mastoid-bowl ears were all smaller than the pressures generated in normal ears; from 250 to 1000 Hz the difference in pressure level was nearly frequency independent and ranged from -3 to -15 dB; from 1000 to 4000 Hz the reduction in level increased with frequency and ranged from -5 dB to -35 dB. In the ears with tympanostomy tubes and perforations the sound pressures were always smaller than in normal ears at frequencies below 1000 Hz; the largest differences occurred below 500 Hz and ranged from -5 to -25 dB. With the supra-aural earphone, the sound pressures in ears with the three pathologic conditions were more variable than those with the insert earphone. Generally, sound pressures in the ears with mastoid bowls were lower than those in normal ears for frequencies below about 500 Hz; above about 500 Hz the pressures showed sharp minima and maxima that were not seen in the normal ears. The ears with tympanostomy tubes and tympanic-membrane perforations also showed reduced ear-canal pressures at the lower frequencies, but at higher frequencies these ear-canal pressures were generally similar to the pressures measured in the normal ears. CONCLUSIONS: When the middle ear is not normal, ear-canal sound pressures can differ by up to 35 dB from the normal-ear value. Because the pressure level generally is decreased in the pathologic conditions that were studied, the measured hearing loss would exaggerate substantially the actual loss in ear sensitivity. The variations depend on the earphone, the middle ear pathology, and frequency. Uncontrolled variations in ear-canal pressure, whether caused by a poor earphone-to-ear connection or by abnormal middle ear impedance, could be corrected with audiometers that measure sound pressures during hearing tests.

Acoustic Impedance Tests↗
PubMed2000

Temporal bone studies of the human peripheral vestibular system. Normative vestibular hair cell data.

Quantitative studies of the vestibular system with serially sectioned human temporal bones have been limited because of difficulty in distinguishing hair cells from supporting cells and type I from type II hair cells. In addition, there is only a limited amount of normative data available regarding vestibular hair cell counts in humans. In this study, archival temporal bone sections were examined by Nomarski (differential interference contrast) microscopy, which permitted visualization of the cuticular plate and stereociliary bundle so as to allow unambiguous identification of hair cells. The density of type I, type II, and total numbers of vestibular hair cells in each of the 5 sense organs was determined in a set of 67 normal temporal bones that ranged from birth through 100 years of age. The mean total densities at birth were 76 to 79 cells per 0.01 mm2 in the cristae, 68 cells per 0.01 mm2 in the utricle, and 61 cells per 0.01 mm2 in the saccule. The ratio of type I to type II hair cells at birth was 2.4:1 in the cristae and 1.3:1 in the maculae. There was a highly significant age-related decline in all sense organs for total, type I, and type II hair cell densities that was best fit by a linear regression model. The cristae lost type I cells with advancing age at a significantly greater rate than the maculae, whereas age-related losses for type II cells occurred at the same rate for all 5 sense organs. Hair cell densities in the cristae were significantly higher at the periphery than at the center. There were no significant sex or interaural differences for any of the counts. Mathematical models were developed to calculate the mean and 95% prediction intervals for the total, type I, and type II hair cell densities in each sense organ on the basis of age. There was overall good agreement between the hair cell densities determined in this study and those reported by others using surface preparation techniques. Our data and related models will serve as a normative database that will be useful for comparison to counts made from subjects with known vestibular disorders.

Adolescent↗
PubMed2000

Temporal bone studies of the human peripheral vestibular system. Normative Scarpa's ganglion cell data.

Scarpa's ganglion cell counts were performed in 106 serially sectioned, normal human temporal bones from 75 individuals. Of these 106 bones, 15 were from neonates less than 30 days old, 14 were from infants between the ages of 1 and 12 months, and the remainder were distributed throughout each decade of life, with sample sizes ranging from 4 to 10 per decade. All temporal bones had to meet 2 criteria: no symptoms or signs of inner ear disease except for presbycusis in the medical case history and no abnormality in the inner ear on light microscopy. The total ganglion cell counts declined significantly with age at an average rate of 57 cells per year. The age-related decline was significantly greater in the superior division than in the inferior division. There was also a significant sex effect, independent of age: for any age, the count in men averaged 1,526 cells higher than in women. There was no significant interaural difference. Mathematical models were developed to compute the mean and 95% prediction intervals for Scarpa's ganglion cell counts in terms of age and sex parameters. The counts and models will serve as a normative database against which to compare counts made in temporal bones from subjects with known vestibular disorders.

Adolescent↗