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Biomedical subjects

S J O'Leary

Publications and source records attributed to S J O'Leary.

At least 19 recordsLinked to original sources

A comparison of the monothermal and bithermal caloric tests.

This study considered whether the monothermal (MT) caloric test could predict the normality of the full conventional bithermal (BT) caloric test, and therefore be an alternative to full caloric investigation. This would have the advantages of reducing test time and patient discomfort as only two caloric tests would be needed instead of four. 744 BT caloric investigations were examined, and the unilateral weakness and directional preponderance calculated for the BT and the MT stimuli. By defining the BT results as the standard, the false-positive and false-negative results of the MT test were derived. Overall using very strict MT difference criteria of less than 5% and no spontaneous nystagmus, false-negative rates for the cool MT were very low (< 1%) and better than the warm MT (< 7.1%) suggesting that the cool MT was a reliable screen test. However, unacceptably high false-positive rates were produced reflecting more than 3/4 of normal BT results failing the MT criterion. This unacceptable false-positive rate decided against implementing the MT test at our facility. The results of this study however have guided the use of the cool air-stimulus first during BT testing and, when completion of the BT is not possible or inadvisable, satisfying the stringent MT criterion confidently indicates with a probability of > 99% the absence of an abnormal BT result.

Caloric Tests↗

Functional and morphological response of the stria vascularis following a sensorineural hearing loss.

Cochlear endolymph is maintained at a potential of (+)80 mV by an active transport mechanism involving the stria vascularis (SV). This so-called endocochlear potential (EP) is integral to hair cell transduction. We compared the EP with changes in SV area and Na(+),K(+)-ATPase expression following a sensorineural hearing loss. Guinea pigs were deafened using kanamycin and a loop diuretic, and the EP was measured at two, 14, 56, 112 or 224 days following deafening. Auditory brainstem responses were used to confirm that each animal had a severe-profound hearing loss. There was a significant reduction in EP following two days of deafness (normal, 73.5 mV S.E.M.=2.4; deaf, 42.1 mV, S.E.M.=2.8; P<0.0001, t-test). In animals deafened for 14 days the EP had partially recovered (65.2 mV, S.E.M.=5.08), while animals deafened for longer periods exhibited a complete recovery (56 days 80.5 mV, S.E.M.=5.36; 112 days 75.7 mV, S.E.M.=2.71; 224 days 81.0 mV; S.E.M.=6.0). Despite this recovery, there was a systematic reduction in SV area with duration of deafness over the first 112 days of deafness. Significant reductions were localised to the basal turn in animals deafened for two days, but had extended to all turns in animals deafened for 112 days. While there was a significant reduction in strial area, the optical density of Na(+),K(+)-ATPase within the remaining SV was normal. Since the treated animals exhibited essentially a complete elimination of all hair cells, the total K(+) leakage current from the scala media would be expected to be significantly reduced. The large reduction in the extent of the SV after deafening suggests that a reduced strial volume is capable of maintaining a normal EP under conditions of reduced K(+) leakage current.

Animals↗

Perilymphatic application of cisplatin over several days in albino guinea pigs: dose-dependency of electrophysiological and morphological effects.

Cisplatin, at 0, 3, 30 or 300 microg/ml in saline, was applied to the scala tympani of the cochlea of guinea pigs via osmotic mini-pumps, operating at a pump rate of 0.5 microl/h. Electrocochleographic recordings were made from an implanted round window electrode. When an electrocochleographic criterion of ototoxicity was reached (40 dB loss in compound action potential (CAP) threshold at 8 kHz), or after 1 week if this criterion was not reached, the animals were sacrificed for light microscopy. A subgroup of animals had endocochlear potentials (EPs) measured prior to sacrifice. Hearing remained stable in the 0 microg/ml control group, but a sudden drop of auditory sensitivity across the whole frequency range was observed in all other groups. It took 1-5 days before the drop occurred, dependent on cisplatin concentration. CAP and cochlear microphonics were lost simultaneously. The EP was severely depressed in the affected animals, suggesting that cisplatin effects on the EP are primary. However, histology revealed an accompanying loss of outer hair cells, primarily in the basal turn. It is concluded that if cisplatin is given until ototoxicity becomes apparent electrophysiologically, then the cochlear pathology from intrascalar cisplatin administration resembles that from daily parenteral administration at 1.5-2.0 mg/kg. The cochlear pathology from the parenteral treatment was greater than that observed with 30 microg/ml pumps, and less than that from 300 microg/ml pumps.

Action Potentials↗

Reversible cisplatin ototoxicity in the albino guinea pig.

Guinea pigs implanted with round window electrodes received daily doses (2.0 mg/kg) of cisplatin until a profound hearing loss occurred (> 40 dB at 8 kHz). Afterwards, pronounced recovery occurred. Recovery progressed over intervals up to 3 weeks before it saturated. Loss and recovery involved both the compound action potential and, less pronounced, the cochlear microphonics. Cochlear potentials evoked by lower frequencies recovered more fully than those evoked by higher frequencies. Loss and recovery was found also in the endocochlear potential. Outer hair cell counts did not change over the recovery period. These findings confirm our previously reported results on the reversibility of cisplatin damage. Further, they implicate the vascular stria as an important target for cisplatin in the cochlea.

Action Potentials↗

The photoreduction of H(2)O(2) by Synechococcus sp. PCC 7942 and UTEX 625.

It has been claimed that the sole H(2)O(2)-scavenging system in the cyanobacterium Synechococcus sp. PCC 7942 is a cytosolic catalase-peroxidase. We have measured in vivo activity of a light-dependent peroxidase in Synechococcus sp. PCC 7942 and UTEX 625. The addition of small amounts of H(2)O(2) (2.5 microM) to illuminated cells caused photochemical quenching (qP) of chlorophyll fluorescence that was relieved as the H(2)O(2) was consumed. The qP was maximal at about 50 microM H(2)O(2) with a Michaelis constant of about 7 microM. The H(2)O(2)-dependent qP strongly indicates that photoreduction can be involved in H(2)O(2) decomposition. Catalase-peroxidase activity was found to be almost completely inhibited by 10 microM NH(2)OH with no inhibition of the H(2)O(2)-dependent qP, which actually increased, presumably due to the light-dependent reaction now being the only route for H(2)O(2)-decomposition. When (18)O-labeled H(2)O(2) was presented to cells in the light there was an evolution of (16)O(2), indicative of H(2)(16)O oxidation by PS 2 and formation of photoreductant. In the dark (18)O(2) was evolved from added H(2)(18)O(2) as expected for decomposition by the catalase-peroxidase. This evolution was completely blocked by NH(2)OH, whereas the light-dependent evolution of (16)O(2) during H(2)(18)O(2) decomposition was unaffected.

Ammonium Hydroxide↗

Abnormal positive potentials in round window electrocochleography.

OBJECTIVE: To describe an atypical waveform, termed an abnormal positive potential (APP), on round window electrocochleograms (RW ECochG) of children and to relate its occurrence to clinical history. STUDY DESIGN: APPs were identified prospectively, and a retrospective analysis was made of these patients' clinical histories, audiograms, and auditory outcomes (hearing aid, cochlear implant, or nonauditory communication) SETTING: Tertiary referral teaching hospital, day surgery and clinics. PATIENTS: All 431 children <110 months of age suspected of a severe to profound hearing loss who underwent RW ECochG from January 1993 to August 1997. INTERVENTION: Diagnostic RW ECochG for auditory threshold estimation. MAIN OUTCOME MEASURE: The presence on the RW ECochG of the APP: an early positive potential in the absence of a compound action potential (CAP). RESULTS: An APP was observed in 34 children. The APP was most marked in response to clicks and 8-kHz tones. The APP click threshold averaged 70 dB hearing loss. The brainstem evoked potential of these children showed an absence of waves, or a broad positive wave with no subsequent waves. Twenty-nine of 30 behavioral audiograms obtained were indicative of severe to profound hearing loss. Auditory outcomes were available from 26 children; 45% of them derived no help from a hearing aid, and 8 children received a cochlear implant. Clinical factors frequently associated with APP were prematurity in combination with kemicterus or hypoxia. CONCLUSIONS: APP thresholds were lower than neural thresholds or behavioral thresholds. Children with APP need close follow-up, because half of those studied needed nonauditory strategies to develop effective communication.

Audiometry, Evoked Response↗

Surviving cochlear function in the presence of auditory nerve agenesis.

This case reports electrophysiological evidence for cochlear function in a child with radiological evidence of bilateral auditory nerve agenesis or severe hypoplasia. The diagnosis of auditory nerve agenesis was supported by a bilateral atresia of internal auditory canals on computed tomography (CT) scan and magnetic resonance imaging (MRI) absent auditory brainstem responses and absent behavioural responses to sound. Despite the apparent absence of an auditory nerve or spiral ganglion, electrocochleography revealed surviving cochlear function at 70-80 db HL and an abnormal electrocochleographic waveform. This case demonstrates that cochlear function may develop without afferent, or efferent innervation. It also emphasizes that cochlear function may occur in the presence of profound deafness.

Abnormalities, Multiple↗

A stochastic model of the electrically stimulated auditory nerve: single-pulse response.

Most models of neural response to electrical stimulation, such as the Hodgkin-Huxley equations, are deterministic, despite significant physiological evidence for the existence of stochastic activity. For instance, the range of discharge probabilities measured in response to single electrical pulses cannot be explained at all by deterministic models. Furthermore, there is growing evidence that the stochastic component of auditory nerve response to electrical stimulation may be fundamental to functionally significant physiological and psychophysical phenomena. In this paper we present a simple and computationally efficient stochastic model of single-fiber response to single biphasic electrical pulses, based on a deterministic threshold model of action potential generation. Comparisons with physiological data from cat auditory nerve fibers are made, and it is shown that the stochastic model predicts discharge probabilities measured in response to single biphasic pulses more accurately than does the equivalent deterministic model. In addition, physiological data show an increase in stochastic activity with increasing pulse width of anodic/cathodic biphasic pulses, a phenomenon not present for monophasic stimuli. These and other data from the auditory nerve are then used to develop a population model of the total auditory nerve, where each fiber is described by the single-fiber model.

Action Potentials↗

A stochastic model of the electrically stimulated auditory nerve: pulse-train response.

The single-pulse model of the companion paper [1] is extended to describe responses to pulse trains by introducing a phenomenological refractory mechanism. Comparisons with physiological data from cat auditory nerve fibers are made for pulse rates between 100 and 800 pulses/s. First, it is shown that both the shape and slope of mean discharge rate curves are better predicted by the stochastic model than by the deterministic model. Second, while interpulse effects such as refractory effects do indeed increase the dynamic range at higher pulse rates, both the physiological data and the model indicate that much of the dynamic range for pulse-train stimuli is due to stochastic activity. Third, it is shown that the stochastic model is able to predict the general magnitude and behavior of variance in discharge rate as a function of pulse rate, while the deterministic model predicts no variance at all.

Analysis of Variance↗

The effects of stochastic neural activity in a model predicting intensity perception with cochlear implants: low-rate stimulation.

Most models of auditory nerve response to electrical stimulation are deterministic, despite significant physiological evidence for stochastic activity. Furthermore, psychophysical models and analyses of physiological data using deterministic descriptions do not accurately predict many psychophysical phenomena. In this paper we investigate whether inclusion of stochastic activity in neural models improves such predictions. To avoid the complication of interpulse interactions and to enable the use of a simpler and faster auditory nerve model we restrict our investigation to single pulses and low-rate (< 200 pulses/s) pulse trains. We apply signal detection theory to produce direct predictions of behavioral threshold, dynamic range and intensity difference limen. Specifically, we investigate threshold versus pulse duration (the strength-duration characteristics), threshold and uncomfortable loudness (and the corresponding dynamic range) versus phase duration, the effects of electrode configuration on dynamic range and on strength-duration, threshold versus number of pulses (the temporal-integration characteristics), intensity difference limen as a function of loudness, and the effects of neural survival on these measures. For all psychophysical measures investigated, the inclusion of stochastic activity in the auditory nerve model was found to produce more accurate predictions.

Cochlear Implants↗

Development of cochlear sensitivity to aminoglycoside antibiotics.

This study examined the temporal relationship between aminoglycoside ototoxicity and the onset of auditory function in the rat. A single dose of gentamicin sulfate (200 mg/kg) and furosemide (100 mg/kg) was administered on postnatal day 6 (P6), P7, P8, P9, or P10, just before the onset of auditory function. Ototoxicity was assessed by the elevation of auditory brain stem response (ABR) thresholds, recorded once the rats had matured. The ABRs were evoked by acoustic clicks and tone pips. The thresholds of control and P6- and P7-treated animals did not differ significantly from each other. Thresholds of some P8- and all P9-treated animals were elevated. The P10-treated animals were deafened, according to these ABR criteria. These data suggest that the potential for aminoglycoside ototoxicity develops rapidly between P8 and P10, just before the onset of auditory function.

Animals↗

Loss of cochlear nucleus neurons following aminoglycoside antibiotics or cochlear removal.

This study compared the effects of aminoglycoside ototoxicity and surgical ablation of the cochlea in infancy on the survival of neurons in the rat cochlear nucleus (CN). Ototoxicity was induced by a single, systemic dose of gentamicin sulfate and furosemide on postnatal day 6 (P6), P7, or P10, and assessed by the elevation of auditory brain stem response thresholds, as described in a companion paper. Unilateral cochlear removals were performed under Saffan anesthesia on P6, P9, and P12. Rats were painlessly sacrificed in adulthood, and the formalin-perfused brains and cochleas were embedded in wax, sectioned, and stained. Ototoxic treatment at P6 through P10 did not reduce neuron counts in the CN. Cochlear removal at P6 resulted in a 40% loss of CN neurons, but removal at P12 did not result in CN neuron loss. These data suggest that the critical period for the dependence of CN neurons on afferent input from the cochlea ends at the same time that susceptibility to aminoglycoside ototoxicity begins.

Animals↗

Responses of dorsal cochlear nucleus single units to electrical pulse train stimulation of the auditory nerve with a cochlear implant electrode.

In response to 100-ms duration electrical stimulation within the range 50-400 pulses per second (pps), and at 1.6- to 2.4-mA stimulus current, a range of poststimulus time histogram (PSTH) patterns were observed from dorsal cochlear nucleus (DCN) units, they were usually primarylike, onset or "negative response" and occasionally buildup or pauser patterns. It appeared that the excitatory and suppressive processes, also termed neural drives, in response to 2.5-pps electrical stimulation were the main determinants of DCN unit responses to 50- to 400-pps stimulation. This was demonstrated by a model of DCN responses to electrical stimulation of the auditory nerve. The neural drives required to model the PSTH patterns were (i) an excitatory process with a latency of < 5 ms, (ii) a second excitatory process latency of 4.5-10 ms, (iii) a long acting suppressive process with a latency of < 15 ms and a duration of > 70 ms, (iv) a short acting suppressive response with a latency of 2.5-3.7 ms and a duration usually < 5 ms, but always < 20, and (v) a drive contributing spontaneous activity to the unit. In addition to these processes which were observed at 2.5 pps, an additional, transient suppressive process was postulated to operate only at 50-400 pps. It was postulated that the PSTH patterns observed were due to differences in the strengths of these drives between units.

Animals↗

Model of discharge rate from auditory nerve fibers responding to electrical stimulation of the cochlea: identification of cues for current and time-interval coding.

A model of the response of auditory nerve fibers to electrical stimulation of the cochlea is presented. Auditory nerve fiber responses are described in terms of cochlear regions activated by the stimulus: region A, in which the discharge rate equals a value of the pulse rate plus spontaneous activity, and region B, in which the discharge rate is less than pulse rate plus spontaneous activity but greater than spontaneous activity. The cues for intensity and time-interval coding provided by regions A and B are discussed.

Auditory Pathways↗

Discharge rate-level functions from dorsal cochlear nucleus single units in response to acoustic and electrical stimulation of the auditory nerve.

Discharge rate-level (I/O) functions possessed by dorsal cochlear nucleus (DCN) units were examined, in response to bipolar electrical stimulation of the cochlea of the barbiturate-anesthetized cat. Spontaneously active units usually possessed nonmonotonic functions with a minimum, and spontaneously inactive units usually possessed monotonic functions or nonmonotonic functions with a maximum (NM+). In response to acoustic high-pass filtered noise, the function relating discharge rate and cutoff frequency resembled the same unit's I/O function to electrical stimulation. The I/O functions to acoustic characteristic tones were usually monotonic or NM+. These results suggest that in the DCN, a prerequisite for the generation of acoustic-like responses with an electrical stimulus may be the matching of the cochlear place and spatial extent activated by each stimulus.

Acoustic Stimulation↗

Neural processes in the dorsal cochlear nucleus of the anaesthetised cat investigated from unit responses to electrical stimulation of the auditory nerve.

Extracellular responses of dorsal cochlear nucleus single units were recorded in response to biphasic, bipolar electrical stimulation of spiral ganglion cells and their peripheral processes using a banded electrode array in the scala tympani of the barbiturate anaesthetised cat. The DCN responses to this stimulus were the result of excitatory and suppressive (including inhibitory) processes. The excitatory responses from DCN units were usually within a range of 1.8-2.8 ms and these responses were probably the result of monosynaptic input from the auditory nerve. Latencies > 2.8 ms were most likely due to activation of di- and poly-synaptic pathways from auditory nerve fibres, except that latencies between 3.5-4.75 in hearing animals could have arisen from electrophonic mechanisms. Suppression of spontaneous activity was usually long acting, lasting > 70 ms following each pulse of the pulse train, but short acting suppression with a latency of 3.5-4.75 ms and a duration of < 10 ms was occasionally observed. These suppressive responses probably resulted from synaptic inhibitory input, but neural membrane properties may have contributed. In hearing animals, excitatory latencies within the range 1.8-5.2 ms were similar for units with different response area types or different PSTH patterns in response to acoustic CF tones or noise.

Acoustic Stimulation↗

The role of managed care in integrated delivery networks.

Health care reform, especially if as anticipated via a capitated payment system, will lead providers to integrate the services they provide to the community with those of other organizations. Vertical integration strategies, such as the formation of physician-hospital organizations, and horizontal integration through alliances and holding companies, are the primary vehicles that hospitals and other providers will use to establish integrated networks. By including insurers and primary care physicians in the network and developing information systems to support the delivery of high quality, cost-effective services, the networks can offer a full continuum of care and minimize service duplication.

Comprehensive Health Care↗