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Cochlear implants rely on the integrity and correct functioning of auditory nerves. However, after sensorineural hearing loss there is a well-characterised degeneration of auditory nerves. One proposed mechanism of this degeneration is a reduction in the levels of neurotrophins, which are naturally occurring proteins that aid the growth and maintenance of neurons. Neurotrophin application to the cochlea of animals prevent morphological degeneration of the auditory nerves after deafness, making it a promising treatment for improving cochlear implant outcomes. The current study examined the effects of two major neurotrophins present in the cochlea, brain-derived neurotrophic factor and neurotrophic factor-3, on the function of individual auditory nerve fibres to cochlear implant stimulation. Guinea pigs were ototoxically deafened and then divided into groups that received treatment for four weeks with either brain derived neurotrophic factor, neurotrophin factor-3 or Ringer's solution as a control. Treatments were administered one week after deafening and delivered to the left cochlea through a combined cannula-electrode array that was attached to a mini-osmotic pump. Additional control groups included guinea pigs deafened for five weeks and an acutely deafened group. At the end of the treatment period responses of individual auditory nerve fibres to acute electrical stimulation of the cochlea at rates from 200-5000 pulses per second were recorded. Both brain derived neurotrophic factor and neurotrophin-3 treatment generally normalized the reduction in spike latency of auditory nerve fibres observed after deafness. BDNF significantly reduced thresholds compared to all control groups, while NT-3 did not. Both BDNF and NT-3 increased the first-spike dynamic range compared to untreated groups. These results were largely similar regardless of the stimulus rate used. These results suggest that neurotrophin treatment of the cochlea after deafness appears to preserve the latency of auditory nerve fibres, but may alter the response threshold and dynamic range. Further investigations are required to determine if neurotrophins are likely to preserve or improve auditory nerve function when used with a cochlear implant. [ABSTRACT FROM AUTHOR]

Although a previous genetic mixed-stock analysis (gMSA) conducted in the early 1990s showed that marine-captured New York Bight Atlantic sturgeon Acipenser oxyrinchus oxyrinchus almost exclusively originated from the Hudson River, fish from southern U.S. rivers were well represented within this contemporary sample ( n = 364 fish), at least during the autumn. Widely distributed spawning stocks are therefore exposed to heavy fishing activity and habitat degradation in this relatively small area, illustrating the need for spatial management across multiple management jurisdictions and routine gMSA to account for temporal change. [ABSTRACT FROM AUTHOR]

This prospective, double-blind controlled, randomized clinical trial of 43 adults showed that topical methylprednisolone applied to the round window during cochlear implantation was effective in protecting inner ear function. Postoperative vestibular disturbance was significantly lower in the steroid group (5%) than the control group (29%). Electrode impedances from the middle portion of the electrode array (electrodes 10-13) were significantly reduced in steroid-treated recipients compared to controls. Hearing and vestibular function analyses were under-powered to detect any drug changes due to limited participant data. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Fluctuations in cochlear implant impedance are associated with inner ear pathology after implantation. The current research explores whether these fluctuations coincide with episodes of hearing loss and/or vertigo, with a comparison between lateral wall and peri-modiolar electrode arrays. Seven-hundred and seventy recipients of Cochlear's slimstraight, lateral wall electrode (CI422) or peri-modiolar (CI512) electrode were investigated for impedance fluctuations. Impedance fluctuations were defined as a median rise of ≥ 4 kΩ across all intra-cochlear electrodes from baseline measurements taken two weeks after switch-on. Medical records were analysed from 193 of the 770 patients selected so that a comparable number would have impedance fluctuations as did not, for both electrode types. The slim straight, lateral wall electrode was found to fluctuate in impedance at a small, but significantly higher rate than the peri-modiolar array (17% vs 12% respectively). Impedance fluctuations were found to significantly correlate with medical events (either hearing loss, vertigo, or tinnitus). Overall, in the "fluctuation" group, 42 out of 75 patients (56%) demonstrated a clinical event during the impedance fluctuation, whereas 26 out of 118 patients (22%) of the "non-fluctuation" group had a clinical event. This significant difference existed with both implant type. The Positive Predictive Value (PPV) of the impedance fluctuation being associated with a clinical event is 0.56, and the Negative Predictive Value (NPV) is 0.78. There were no significant differences in the demographics of those who had an impedance fluctuation compared with those who did not. These results support the relationship between fluctuations in cochlear implant impedances and post-operative clinical events, including the loss of residual hearing and vertigo. Monitoring cochlear implant impedance may be a method for early detection, and so the prevention, of these events in the future. [ABSTRACT FROM AUTHOR]

Objective: To describe the experience and outcomes with the Slim Modiolar cochlear Implant Electrode. Materials and Methods: Retrospective review of all patients receiving the new CI532 implant. Outcome measures include; pre and postoperative speech perception, operative report details, electrode position as determined by X-ray in all cases and also Cone Beam CT in adults. Comparison was made with prior experience with the Contour perimodiolar CI512 electrode. Results: 135 CI532 implants were implanted prior to 30/01/2018. 43 in children and 92 in adults. Tip fold over occurred in 6 cases (4.4%). 4 were recognized and corrected intra-operatively, 2 recognized on post op CBCT required revision surgery. Of the 92 adults, CBCT confirmed scala tympani position in all but one case where placement had been into scala vestibuli. There were no translocations from ST to SV. This compares favourably with CI512 translocation rate of 17%. Speech perception outcomes demonstrated good performance with mean pre-op phoneme scores of 21.8 (+/- 15) increasing to 3 month post op of 61.2% (+/- 23). Where 12 month phoneme scores are available, CI532 compared favourably with a matched group of 512 recipients, 79.5 (14) vs 69.4 (17) respectively. Conclusion: The slim modiolar, CI532 electrode has provided very reliable scala tympani position with a low rate of tip fold over. The speech perception outcomes achieved compare favourably with our experience with previous perimodiolar electrodes. [ABSTRACT FROM AUTHOR]

Aim: To explore morphological or electrophysiological evidence for the presence of endolymphatic hydrops (EH) in guinea pig cochleae in the first 3 months after cochlear implantation., Methods: Dummy silastic electrodes were implanted atraumatically into the basal turn of scala tympani via a cochleostomy. Round window electrocochleography (ECochG) was undertaken prior to and after implantation. Animals survived for 1, 7, 28 or 72 days prior to a terminal experiment, when ECochG was repeated. The cochleae were imaged using micro-CT after post-fixing with osmium tetroxide to reveal the inner ear soft tissue structure. EH was assessed by visual inspection at a series of frequency specific places along the length of the cochlea, and the extent to which Reissner's membrane departed from its neutral position was quantified. Tissue response volumes were calculated. Using ECochG, the ratio of the summating potential to the action potential (SP/AP ratio) was calculated in response to frequencies between 2 and 32 kHz., Results: There was minimal evidence of electrode trauma from cochlear implantation on micro-CT imaging. Tissue response volumes did not change over time. EH was most prevalent 7 days after surgery in implanted ears, as determined by visual inspection. Scala media areas were increased, as expected in cases of EH, over the first month after cochlear implantation. SP/AP ratios decreased immediately after surgery, but were elevated 1 and 7 days after implantation., Conclusions: EH is prevalent in the first weeks after implant surgery, even in the absence of significant electrode insertion trauma., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Aims: The objective of the study was to isolate the microalgae strains from treated municipal wastewater in both summer and winter seasons in order to identify strains better suited for nutrient remediation and biofuel production under either cooler or warmer temperatures., Methods and Results: Fifty-six strains in total were isolated and identified by DNA sequencing from effluent samples collected from a local wastewater treatment plant during the summer and winter of 2011. Screening of 41 isolates based on the fatty acid productivity at either 22 or 10°C resulted in the selection of 12 strains organized into two groups of 6-the M (mild) and C (cool) groups, respectively. Four of the C-group strains were isolated from the winter sample, while four of the M-group isolates were isolated from the summer sample. Fatty acid pools in M-group strains were heavily regulated in response to growth temperature while C-group strains were more insensitive. In three of the six C-group strains, the rates of biomass and fatty acid productivity at 10°C exceeded the corresponding rates at 22°C. Conversely, M group were always more productive at 22 compared to 10°C. Mixotrophic strategies to enhance productivity were generally unsuccessful in M-group strains at 22°C but proved to be more effective in C-group cultures at 10°C., Conclusions: In general, C-group strains appeared better suited for growth in municipal wastewater at 10°C, while M-group strains were better suited at 22°C. On balance, C-group isolates were more likely to come from winter wastewater samples while M-group strains were more likely to come from the summer sample., Significance and Impact of the Study: Our results demonstrate that the effects of temperature on microalgal growth for wastewater remediation can be mitigated somewhat by isolation and careful selection of strains adapted to seasonal wastewater conditions., (© 2015 Her Majesty the Queen in Right of Canada © 2015 The Society for Applied Microbiology. Reproduced with the permission of the Director General of the National Research Council Canada.)

Clinically, gentamicin has been used extensively to treat the debilitating symptoms of Mèniére's disease and is well known for its vestibulotoxic properties. Until recently, it was widely accepted that the round window membrane (RWM) was the primary entry route into the inner ear following intratympanic drug administration. In the current study, gentamicin was delivered to either the RWM or the stapes footplate of guinea pigs (GPs) to assess the associated hearing loss and histopathology associated with each procedure. Vestibulotoxicity of the utricular macula, saccular macula, and crista ampullaris in the posterior semicircular canal were assessed quantitatively with density counts of hair cells, supporting cells, and stereocilia in histological sections. Cochleotoxicity was assessed quantitatively by changes in threshold of auditory brainstem responses (ABR), along with hair cell and spiral ganglion cell counts in the basal and second turns of the cochlea. Animals receiving gentamicin applied to the stapes footplate exhibited markedly higher levels of hearing loss between 8 and 32 kHz, a greater reduction of outer hair cells in the basal turn of the cochlea and fewer normal type I cells in the utricle in the vestibule than those receiving gentamicin on the RWM or saline controls. This suggests that gentamicin more readily enters the ear when applied to the stapes footplate compared with RWM application. These data provide a potential explanation for why gentamicin preferentially ablates vestibular function while preserving hearing following transtympanic administration in humans., (Copyright © 2013 Elsevier B.V. All rights reserved.)

This study reviews the cochlear histology from four hearing preservation cochlear implantation experiments conducted on 73 guinea pigs from our institution, and relates histopathological findings to residual hearing. All guinea pigs had normal hearing prior to surgery and underwent cochlear implantation via a cochleostomy with a silastic-platinum dummy electrode. Pure tone auditory brainstem response (ABR) thresholds from 2 to 32 kHz were recorded prior to surgery, and at one and four weeks postoperatively. The cochleae were then fixed in paraformaldehyde, decalcified, paraffin embedded, and mid-modiolar sections were prepared. The treatment groups were as follows: 1) Systemic dexamethasone, 0.2 mg/kg administered 1 h before implantation, 2) Local dexamethasone, 2% applied topically to the round window for 30 min prior to cochlear implantation, 3) Local n-acetyl cysteine, 200 μg applied topically to the round window for 30 min prior to implantation, 4) inoculation to keyhole-limpet hemocyanin (KLH) prior to implantation, and 5) untreated controls. There was a significant correlation between the extent of the tissue reaction in the cochlea and the presence of foreign body giant cells (FBGCs), new bone formation and injury to the osseous spiral lamina (OSL). The extent of the tissue response, as a percentage of the area of the scala tympani, limited the best hearing that was observed four weeks after cochlear implantation. Poorer hearing at four weeks correlated with a more extensive tissue response, lower outer hair cell (OHC) counts and OSL injury in the basal turn. Progressive hearing loss was also correlated with the extent of tissue response. Hearing at 2 kHz, which corresponds to the region of the second cochlear turn, did not correspond with loco-regional inner hair cell (IHC), OHC or SGC counts. We conclude that cochlear injury is associated with poorer hearing early after implantation. The tissue response is related to indices of cochlear inflammation and injury. An extensive tissue response limits hearing at four weeks, and correlates with progressive hearing loss. These latter effects may be due to inflammation, but would also be consistent with interference of cochlear mechanics., (Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.)

Locally applied drugs can protect residual hearing following cochlear implantation. The influence of cochlear implantation on drug levels in the scala tympani (ST) after round window application was investigated in guinea pigs using the marker trimethylphenylammonium (TMPA) measured in real time with TMPA-selective microelectrodes. TMPA concentration in the upper basal turn of the ST rapidly increased during implantation and then declined due to cerebrospinal fluid entering the ST at the cochlear aqueduct and exiting at the cochleostomy. The TMPA increase was found to be caused by the cochleostomy drilling if the burr tip partially entered the ST. TMPA distribution in the second turn was less affected by implantation procedures. These findings show that basal turn drug levels may be changed during implantation and the changes may need to be considered in the interpretation of therapeutic effects of drugs in conjunction with implantation., (Copyright © 2013 S. Karger AG, Basel.)

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.

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.

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.

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.

In a recent set of modeling studies we have developed a stochastic threshold model of auditory nerve response to single biphasic electrical pulses (Bruce et al., 1999c) and moderate rate (less than 800 pulses per second) pulse trains (Bruce et al., 1999a). In this article we derive an analytical approximation for the single-pulse model, which is then extended to describe the pulse-train model in the case of evenly timed, uniform pulses. This renewal-process description provides an accurate and computationally efficient model of electrical stimulation of single auditory nerve fibers by a cochlear implant that may be extended to other forms of electrical neural stimulation.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

The current distribution of bipolar electrodes implanted into the scala tympani of the cat cochlea was investigated using a two-electrode masking technique. Two electrode masking is a non-invasive technique which requires two electrically independent electrodes and relies upon the forward masking of the electrically evoked brainstem response to a probe stimulus by that of a preceding test stimulus. The technique was described in terms of a model, which enabled an approach for estimating the scala tympani length constant to be established. Model results have shown good agreement with electrophysiological results. Application of the model confirmed the scala tympani length constant within the basal turn of the cochlea to lie between 3 and 4 mm.