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Biomedical subjects

M J McCoy

Publications and source records attributed to M J McCoy.

12 recordsLinked to original sources
PubMed1995

Targeted disruption of the murine VCAM1 gene: essential role of VCAM-1 in chorioallantoic fusion and placentation.

Vascular cell adhesion molecule-1 (VCAM-1) is expressed on vascular endothelium in a variety of inflammatory conditions and mediates leukocyte recruitment from blood into tissues. In this study we report a novel role for VCAM-1 in the formation of the umbilical cord and placenta during development. The murine VCAM1 gene was disrupted by targeted homologous recombination, and a distinct phenotype was found in VCAM-1-deficient embryos. At 8.5 days of gestation, the allantois failed to fuse to the chorion, resulting in abnormal placental development and embryonic death within 1-3 days. In addition, a role for VCAM-1 in early placental formation after chorioallantoic fusion was observed. In a minority of VCAM-1-deficient embryos, the allantois was able to fuse with the chorion, but the allantoic mesoderm was abnormally distributed over the chorionic surface. A small number of VCAM-1-deficient embryos survived, presumably by circumventing the placentation defects. They became viable and fertile adult mice with lack of VCAM-1 expression, normal organs, and an elevated number of circulating blood mononuclear leukocytes.

Allantois↗
PubMed1995

New approaches to the evaluation of the auditory system and a current analysis of otoacoustic emissions.

Healthy ears generate low-level sounds known as otoacoustic emissions that are produced by the normal workings of the inner ear. By placing a specially constructed probe containing an assembly of miniature microphones in the ear canal, hearing investigators can listen to these sounds. Before emissions were discovered, the only methods available to explore the ordinarily inaccessible structures of the cochlea involved invasive and, thus damaging, experiments, which could only be performed on animals. With the discovery of otoacoustic emissions, noninvasive research on the inner ear became possible, thus allowing study of the fundamental processes that determine the excellent sensitivity and fine frequency tuning that are uniquely associated with human hearing. The results of these basic experiments have made it possible to develop a number of useful clinical applications based on emissions testing. One noteworthy benefit is the use of emissions as a screening test that objectively assesses the functional integrity of peripheral processing in patients who are difficult to examine, such as infants and young children. Other applications take advantage of the test's diagnostic strength as an indicator of the sensory component of a sensorineural hearing loss. Finally, because emissions testing can be conducted rapidly and accurately under computer control, it has proved useful in the serial monitoring of ear performance in instances where a progressive hearing impairment is suspected.

Hearing Disorders↗
PubMed1995

Time-windowing of click-evoked otoacoustic emissions to increase signal-to-noise ratio.

OBJECTIVE: To investigate the effects of decreasing the response-window duration on the signal-to-noise ratio (S/N) of click-evoked otoacoustic emissions (CEOAEs). DESIGN: The ILO88 (Otodynamics, Ltd.) was used to measure CEOAEs from 149 normal adult ears, and 75 adult ears with high-frequency sensorineural hearing loss. Data were collected using the default response window of 2.5 to 20.5 msec post-click. Each response was rewindowed, post-hoc, from 2.5 to 7.5 msec, 2.5 to 9 msec, 7.75 to 14.25 msec, and 13 to 19.5 msec post-click. For each window, spectra of the CEOAE and of the background noise were determined. The S/N was estimated by subtracting the noise level from the CEOAE amplitude. RESULTS: The 13- to 19.5-msec window contained little CEOAE energy relative to earlier windows. Relative to the 2.5- to 20.5-msec window, the 2.5- to 7.5- and 2.5- to 9-msec windows reduced noise levels more than CEOAE amplitudes, yielding increased S/N, and greater "reproducibility" values. The increased S/N of the 2.5- to 7.5- and 2.5- to 9-msec windows allowed measurement of greater CEOAE-amplitude reductions in the impaired ears relative to the normal ears. With short-duration windows, click-presentation rate could be increased, allowing more responses to be averaged in a given time, thus further decreasing noise levels. Although click rate was not varied in the present study, the decrease of noise levels is predictable. Accounting for this factor, it is expected that a specified S/N would be obtained about five times faster using the 2.5- to 7.5-msec window with a 7.5-msec interstimulus interval, than when using the default window. CONCLUSIONS: Decreasing the response-window duration substantially increases the measurement efficiency of CEOAEs in adults, and thus may enhance clinical-test performance.

Acoustic Stimulation↗
PubMed1995

Dependence of distortion-product otoacoustic emissions on primary levels in normal and impaired ears. I. Effects of decreasing L2 below L1.

The 2f1-f2 distortion-product otoacoustic emission (DPOAE) is evoked by two primary tones of frequencies f1 < f2, and levels L1 and L2. Previous reports indicate that decreasing L2 below L1 = L2 can; (1) increase DPOAE amplitude in normal ears, and (2) increase the degree to which DPOAE amplitudes are reduced by cochlear trauma. Although both of these factors could be advantageous for clinical applications of DPOAEs, neither has been explored in detail. In the present study, 2f1-f2 DPOAE-amplitude frequency functions were collected from normal and impaired ears of rabbits and humans, with L1 = L2, and with L2 < L1, at each of three values of L1. In rabbits, controlled tonal or noise overexposures were used to produce permanent reductions of DPOAE amplitudes. Comparison of pre- and postexposure DPOAE-amplitude frequency functions demonstrated that the frequency-specific reductions of DPOAEs were enhanced by decreasing L2 below L1. In humans, DPOAE-amplitude frequency functions obtained with the various L1 and L2 combinations were collected from 16 normal ears to provide preliminary normative data for each stimulus-level condition. The L1-L2 that produced the maximum DPOAE amplitude in normal ears was systematically dependent on L1. Thus at most frequencies, decreasing L2 below L1 = L2 substantially reduced mean DPOAE amplitude when L1 > or = 75 dB SPL, but increased mean DPOAE amplitudes at L1 = 65 dB SPL. However, the increase of mean DPOAE amplitude obtained by decreasing L2 below L1 = 65 dB SPL was small, being less than 3.5 dB at most frequencies. More importantly, at L1 = 65 dB SPL, L2 could be decreased considerably below L1 = L2 without reducing mean DPOAE amplitude relative to that at L1 = L2. Inspection of DPOAE-amplitude frequency functions obtained from subjects with mild or moderate sensorineural hearing losses indicated that, in frequency regions of hearing impairment, decreasing L2 below L1 can enhance the degree of reduction of DPOAEs below the corresponding normative amplitudes, without reducing the normative amplitude. It is concluded that decreasing L2 below L1 = L2 has the potential to enhance the performance of DPOAEs in clinical applications.

Acoustic Stimulation↗
PubMed1995

Dependence of distortion-product otoacoustic emissions on primary levels in normal and impaired ears. II. Asymmetry in L1,L2 space.

Previous studies indicate that the amplitude of 2f1-f2 distortion-product otoacoustic emissions (DPOAEs), evoked by two tones of frequencies f1 < f2, demonstrates a complex dependence on the levels (L1 and L2) of the primary tones. In the present study, 2f1-f2 DPOAE amplitudes were measured over a wide range of L1 and L2 in normal human ears, allowing a systematic, level-dependent asymmetry of DPOAE amplitude in L1,L2 space to be characterized. The L1,L2 at which DPOAEs were largest was close to L1 = L2 at high stimulus levels, but moved monotonically toward L1 > L2 as stimulus levels decreased. A related observation was that DPOAE amplitude had a greater dependence on L1 and on L2. These asymmetries were quantified in normal human ears, and compared to the corresponding asymmetries apparent in data from animal models. Recent studies have demonstrated that the reduction of DPOAE amplitude by cochlear trauma is greater when L1 > L2 than when L1 = L2, suggesting that the reduction of DPOAEs by trauma demonstrates an asymmetry in L1,L2 space that is qualitatively similar to that of normative DPOAE amplitude. To investigate this issue, 2f1-f2 DPOAE amplitudes were measured over a wide range of L1 and L2 in rabbit ears pre- and postinjection of the ototoxic loop-diuretic ethacrynic acid. The results indicate that the asymmetry in L1,L2 space of the reduction of DPOAEs by trauma is both qualitatively and quantitatively similar to the asymmetry in L1,L2 space of normative DPOAE amplitude. Specifically, the L1 values that maximized normative DPOAE amplitudes for any specified L2 (or, equivalently, the L1 values that allowed L2 to be minimized for any specified normative DPOAE amplitude) also yielded the greatest reduction of DPOAEs by the diuretic. In humans, the L1 values that maximize normative DPOAE amplitudes for any specified L2 are well approximated by a simple equation, with parameters that vary with frequency and f2/f1. It is suggested that the L1,L2 values defined by this equation may be optimum for use in clinical applications.

Acoustic Stimulation↗
PubMed1995

Monitoring cochlear function intraoperatively using distortion product otoacoustic emissions.

Distortion product otoacoustic emissions (DPOAEs) elicited by a bitonal stimulus complex are low-level sounds that are generated within the cochlea, and are easily measured by a miniature microphone system placed in the external auditory canal. Under conditions of rapid measurement, DPOAEs have been shown in an animal model to be exquisitely sensitive to interruption of the blood supply to the inner ear. Currently, there is no real-time procedure available for monitoring hearing function intraoperatively during neurotologic surgery. The goal of the present study was to determine the utility of DPOAEs in monitoring cochlear status intraoperatively, particularly during procedures commonly used to remove acoustic neuromas. Distortion product otoacoustic emissions were measured pre- and intraoperatively in 11 patients, who were under general anesthesia for a variety of otolaryngologic procedures, including acoustic neuroma resection. High frequency emissions (i.e., > or = 4 kHz) were less affected by the elevated levels of acoustic noise present in the operating-room environment, thus permitting emitted responses to be updated as quickly as every 2 seconds. However, a number of technical problems were encountered and addressed during development of the emission monitoring technique. Despite these difficulties, overall, DPOAEs appear to be a promising adjunct to the intraoperative monitoring of auditory function.

Acoustic Impedance Tests↗
PubMed1994

Angina and myocardial infarction with use of leuprolide acetate.

Use of leuprolide acetate (Lupron) has been associated with angina in men, but there have been no previous reports of angina or myocardial infarction associated with its use in women. The first case of angina and myocardial infarction occurring in a woman undergoing treatment with leuprolide acetate depot is reported.

Adult↗
PubMed1993

Clinical testing of distortion-product otoacoustic emissions.

Otoacoustic emissions have great promise for use in clinical tests of the functional status of outer hair cells, which represent cochlear structures that make a major contribution to the hearing process. A substantial literature is available concerning the evaluation of outer hair cell function by transiently evoked otoacoustic emissions. However, relatively little attention has been focused on the benefits of testing with distortion-product otoacoustic emissions. The purpose of this presentation is to provide knowledge of the principal advantages offered by distortion-product emissions testing.

Acoustic Impedance Tests↗
PubMed1993

Otoacoustic emissions in children with normal ears, middle ear dysfunction, and ventilating tubes.

The clinical utility of otoacoustic emissions (OAEs) has been well established in adults. The purpose of this investigation was to determine the efficacy of OAE testing in children. Distortion-product OAE (DPOAE) audiograms, response/growth functions, and transiently evoked OAEs elicited with clicks were measured from the ears of both healthy volunteers, aged 4 to 13 years, and children with confirmed middle ear disorders. These measures established the means and variabilities for DPOAE and noise-floor amplitudes of normal and diseased young ears. Compared with adult emissions, the healthy young ears exhibited greater mean DPOAE and noise-floor amplitudes. In contrast, ears with type B and type C tympanogram patterns showed absent or markedly reduced OAE amplitudes, when compared with emissions measured in their control counterparts. Finally, ears with ventilating tubes exhibited OAE amplitudes lower than amplitudes from healthy ears, but higher than those of the untreated diseased ears. Although these findings imply that using OAEs to test the outer hair-cell reserve of infected ears is problematic, emitted responses provide useful information concerning the normalcy of middle ear function.

Acoustic Impedance Tests↗
PubMed1992

Test/retest reliability of distortion-product and transiently evoked otoacoustic emissions.

Otoacoustic emissions can be used to study cochlear function in an objective and noninvasive manner. These features of emitted responses have stimulated a great deal of investigation into the utility of evoked emissions as clinical tests of hearing. One practical and essential aspect of any clinical measure is the consistency of its result upon repeated testing of the same individual (i.e., its test/retest reliability). The goal of the present work was to conduct a systematic study of the test/retest reliability of the two evoked emission types, the transiently evoked and the distortion-product otoacoustic emissions, that have the greatest promise of becoming clinically useful. Toward this end, the short- and long-term reliabilities of these two response measures were examined in 12 normally hearing adults. The results of these experiments showed that the consistency of both measures of evoked otoacoustic emissions was generally excellent.

Adult↗