Biomedical subjects

G M Clark

Publications and source records attributed to G M Clark.

At least 55 records · Page 3Linked to original sources

PubMed2000

Pitch estimation by early-deafened subjects using a multiple-electrode cochlear implant.

Numerical estimates of pitch for stimulation of electrodes along the 22-electrode array of the Cochlear Limited cochlear implant were obtained from 18 subjects who became deaf very early in life. Examined were the relationships between subject differences in pitch estimation, subject variables related to auditory deprivation and experience, and speech-perception scores for closed-set monosyllabic words and open-set Bamford-Kowal-Bench (BKB) sentences. Reliability in the estimation procedure was examined by comparing subject performance in pitch estimation with that for loudness estimation for current levels between hearing threshold and comfortable listening level. For 56% of subjects, a tonotopic order of pitch percepts for electrodes on the array was found. A deviant but reliable order of pitch percepts was found for 22% of subjects, and essentially no pitch order was found for the remaining 22% of subjects. Subject differences in pitch estimation were significantly related to the duration of auditory deprivation prior to implantation, with the poorest performance for subjects who had a longer duration of deafness and a later age at implantation. Subjects with no tonotopic order of pitch percepts had the lowest scores for the BKB sentence test, but there were no differences across subjects for monosyllabic words. Performance in pitch estimation for electrodes did not appear to be related to performance in the estimation procedure, as all subjects were successful in loudness estimation for current level.

Adolescent↗

PubMed2000

Calculation of interspike intervals for integrate-and-fire neurons with poisson distribution of synaptic inputs.

We present a new technique for calculating the interspike intervals of integrate-and-fire neurons. There are two new components to this technique. First, the probability density of the summed potential is calculated by integrating over the distribution of arrival times of the afferent post-synaptic potentials (PSPs), rather than using conventional stochastic differential equation techniques. A general formulation of this technique is given in terms of the probability distribution of the inputs and the time course of the postsynaptic response. The expressions are evaluated in the gaussian approximation, which gives results that become more accurate for large numbers of small-amplitude PSPs. Second, the probability density of output spikes, which are generated when the potential reaches threshold, is given in terms of an integral involving a conditional probability density. This expression is a generalization of the renewal equation, but it holds for both leaky neurons and situations in which there is no time-translational invariance. The conditional probability density of the potential is calculated using the same technique of integrating over the distribution of arrival times of the afferent PSPs. For inputs with a Poisson distribution, the known analytic solutions for both the perfect integrator model and the Stein model (which incorporates membrane potential leakage) in the diffusion limit are obtained. The interspike interval distribution may also be calculated numerically for models that incorporate both membrane potential leakage and a finite rise time of the postsynaptic response. Plots of the relationship between input and output firing rates, as well as the coefficient of variation, are given, and inputs with varying rates and amplitudes, including inhibitory inputs, are analyzed. The results indicate that neurons functioning near their critical threshold, where the inputs are just sufficient to cause firing, display a large variability in their spike timings.

Action Potentials↗

PubMed2000

Comparison of young clinical investigators' accuracy and reproducibility when measuring pulmonary and skin surface nodules using a circumferential measurement versus a standard caliper measurement: American Association for Cancer Research/American Society of Clinical Oncology Clinical Trials Workshop.

PURPOSE: The clinical investigator must understand that errors in measuring tumors can greatly affect such clinical-trial end points as tumor response. We performed a prospective, controlled study of tumor measurements that compared circumferential measurements made with a loop planimeter with linear measurements made with a standard caliper. METHODS: Using a cross-over design, 76 clinical oncology fellows/junior oncology faculty members attending a Methods in Clinical Cancer Research Workshop sponsored by the American Association for Cancer Research and the American Society of Clinical Oncology measured five pulmonary nodule phantoms that ranged in size from 1.76 to 13.21 cm(2) and five surface nodule phantoms with sizes ranging from 2.3 to 12.9 cm(2). To perform these measurements, they used both a loop planimeter and a caliper. Forty-two and 40 participants repeated measurements 3 days later on pulmonary and surface nodules. Accuracy, reproducibility, and time efficiency were evaluated. RESULTS: The linear caliper measurements overestimated pulmonary nodule and surface nodule size by a median of 37% and 23%, respectively. Circumferential loop planimeter measurements overestimated pulmonary nodule size and surface nodule size by a median of 8% and 17%, respectively. Interobserver reproducibility for the planimeter was greater than that for the caliper, as evidenced by thinner measurement interquartile ranges. Furthermore, intraobserver reproducibility was higher for the planimeter, with its variability being only 31.4% and 25.5% as large as that of the caliper when measuring the pulmonary and surface nodules, respectively. CONCLUSION: Circumferential measurements provide better accuracy, reproducibility, and speed in measuring both pulmonary and surface nodules than do perpendicular diameters.

Adult↗

PubMed2000

Prognostic value of p53 for local failure in mastectomy-treated breast cancer patients.

PURPOSE: The loss of p53 function is a recognized adverse prognostic factor in invasive breast cancer. Several studies have shown a relationship between the nuclear accumulation of p53 protein (a surrogate marker of p53 inactivation) and poor disease-free and overall survival. In general, however, these studies did not report the prognostic value of p53 for local failure, which we have therefore assessed retrospectively here. MATERIALS AND METHODS: Accumulation of p53 protein was evaluated by immunohistochemistry in 1,530 mastectomy-treated breast cancer patients (259 radiation therapy [RT]- and 1,271 mastectomy only [No RT]-treated patients). Statistical comparisons were made between p53 protein accumulation, estrogen/progesterone receptors, nodal status, tumor size, and local failure rate (LFR). Local failure was defined as tumor recurrence involving the chest wall and/or the ipsilateral supraclavicular/axillary lymph nodes. The median follow-up period was 62 months. RESULTS: In the No RT group, the LFR was 9.1% and 16. 5% in p53-negative and p53-positive patients, respectively (P<.001). Multivariate analysis revealed that p53 protein accumulation was significantly associated with an increased risk of local relapse (relative risk [RR], 1.7; 95% confidence interval [CI], 1.2 to 2.4). Nodal status and tumor size were also significant factors. In the RT group, the LFR was 9.3% and 21.5% in p53-negative and p53-positive patients, respectively (P = .009). Multivariate analysis revealed that p53 protein accumulation was significantly associated with an increased risk of local relapse (RR, 2.5; 95% CI, 1.1 to 5.7), as was nodal status. CONCLUSION: Nuclear accumulation of p53 protein is independently associated with a significantly increased local failure rate in breast cancer patients treated with mastectomy, with or without radiation.

Adult↗

PubMed2000

Multichannel auditory brainstem implantation: the Australian experience.

The multichannel auditory brainstem implant (ABI) provides the potential for hearing restoration in patients with neurofibromatosis type 2 (NF2). Programmes for auditory brainstem implantation have been established in two Australian centres. Eight patients have been implanted under the protocol of an international multi-centre clinical trial. Three patients had ABI insertion at the time of first side tumour removal, four at second side tumour removal and one after previous bilateral surgery where there was some residual tumour. The translabyrinthine approach was used in all cases. Successful positioning of the electrode array was achieved in seven of eight patients, all of whom achieved auditory perception with electrical stimulation. Intra-operative electrically evoked auditory brainstem response testing was successful in four patients and was useful in confirming correct electrode position. In six cases post-operative psychophysical and auditory perception testing demonstrated that useful auditory sensations were achieved. Five of these patients regularly used the implant. In one patient electrode placement was unsuccessful and only non-auditory sensations occurred on stimulation. In the remaining patients non-auditory sensations were minimal and avoidable by selective electrode programming. Auditory brainstem implantation should be considered in patients with NF2. The greatest benefit is seen in patients without debilitating disease who have non-aidable hearing in the contralateral ear.

Adolescent↗

PubMed2000

Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999.

BACKGROUND: Under the auspices of the College of American Pathologists, a multidisciplinary group of clinicians, pathologists, and statisticians considered prognostic and predictive factors in breast cancer and stratified them into categories reflecting the strength of published evidence. MATERIALS AND METHODS: Factors were ranked according to previously established College of American Pathologists categorical rankings: category I, factors proven to be of prognostic import and useful in clinical patient management; category II, factors that had been extensively studied biologically and clinically, but whose import remains to be validated in statistically robust studies; and category III, all other factors not sufficiently studied to demonstrate their prognostic value. Factors in categories I and II were considered with respect to variations in methods of analysis, interpretation of findings, reporting of data, and statistical evaluation. For each factor, detailed recommendations for improvement were made. Recommendations were based on the following aims: (1) increasing uniformity and completeness of pathologic evaluation of tumor specimens, (2) enhancing the quality of data collected about existing prognostic factors, and (3) improving patient care. RESULTS AND CONCLUSIONS: Factors ranked in category I included TNM staging information, histologic grade, histologic type, mitotic figure counts, and hormone receptor status. Category II factors included c-erbB-2 (Her2-neu), proliferation markers, lymphatic and vascular channel invasion, and p53. Factors in category III included DNA ploidy analysis, microvessel density, epidermal growth factor receptor, transforming growth factor-alpha, bcl-2, pS2, and cathepsin D. This report constitutes a detailed outline of the findings and recommendations of the consensus conference group, organized according to structural guidelines as defined.

Breast Neoplasms↗

PubMed2000

Statistical issues in tumor marker studies.

CONTEXT: Inferences from tumor marker studies are complicated by a variety of statistical concerns, which can make proper interpretation of results difficult. This article focuses on important issues that should be addressed when designing, conducting, and analyzing tumor marker studies. OBJECTIVE: To highlight the importance of considering statistical significance, risk ratios, statistical power, reproducibility, multiple testing, confirmatory studies, and missing data in the design of marker studies used for prognosis. RESULTS: Suggestions are provided for more effectively conducting marker studies. These include more careful attention to adequacy of the number of subjects for a marker study and improved documentation and standardization of assay methods. The importance of complete reporting of study results and description of the statistical analysis methods used is also emphasized. CONCLUSION: Cooperation among clinicians, laboratory scientists, and statisticians will be required to conduct statistically sound tumor marker studies and to facilitate prioritizing markers for new and confirmatory studies in an environment of limited patient and specimen resources.

Biomarkers, Tumor↗

PubMed2000

Cochlear view: postoperative radiography for cochlear implantation.

OBJECTIVE: This study aimed to define a spatial position of the cochlea in the skull based on anatomical studies and to design an appropriate method of skull radiography for demonstration of the multichannel intracochlear electrode array and the structures of the inner ear, for use in evaluating the electrode position and its related pitch perception. BACKGROUND: The conventional skull radiograph (plain radiograph) can offer a complete and direct image of an intracochlear electrode array, if the x-ray is directed to the cochlea and parallel to the axis of the cochlea. METHODS: Measurement from computed tomography imaging and three-dimensional reconstruction were performed to define the spatial position of the cochlea in the skull. RESULTS: A radiographic projection, the cochlear view, was designed. A detailed radiographic method and radiologic interpretation of the cochlear view is described. An improved clinical method for measuring the longitudinal and angular position of the electrodes from the cochlear view is recommended. CONCLUSIONS: The application of the cochlear view has proved that it is beneficial postoperatively in documenting the results of cochlear implantation, and in evaluating the depth of insertion and position of individual electrodes. It serves as a valuable reference for managing frequency mapping, optimizing speech processing strategies, and further research purposes. The method can be widely used in cochlear implant clinics because of its simplicity, low radiation, speed, and minimal cost.

Adolescent↗

PubMed2000

Elevated levels of p66 Shc are found in breast cancer cell lines and primary tumors with high metastatic potential.

The adapter molecule Shc has been implicated in specific steps of metastasis. In the current study, we show that the expression and activation of the p66 Shc isoform increased in a highly metastatic variant (F-11) of the human breast cancer cell line MDA-MB-231 compared to the parent cell line, whereas the p46 and p52 Shc isoforms were unchanged. Despite reports that p66 Shc can negatively regulate epidermal growth factor signaling to the mitogen-activated protein kinase pathway, we found no change in epidermal growth factor-stimulated activation of mitogen-activated protein kinase in the F-11 cell line. We determined the level of Shc expression by immunoblot in primary breast cancer specimens obtained from patients with or without axillary node involvement. p66 Shc expression increased in tumors obtained from node-positive patients (Spearman correlation coefficient = 0.43377; P = 0.0058) compared to the node-negative specimens. Furthermore, increasing levels of p66 Shc correlated with an increasing number of positive nodes (P = 0.032). This study shows that p66 Shc expression increased in cultured breast cancer cells selected for metastasis and in primary human breast cancer specimens obtained from patients with lymph node involvement, suggesting a possible role for Shc in human breast cancer metastasis.

Adaptor Proteins, Signal Transducing↗

PubMed2000

A comparative study of skeletal and dental stability between rigid and wire fixation for mandibular advancement.

This study examined the skeletal and dental stability after mandibular advancement surgery with rigid or wire fixation for up to 2 years after the surgery. Subjects for this multisite, prospective, randomized, clinical trial were assigned to receive rigid (n = 64) or wire (n = 63) fixation. The rigid cases received three 2-mm bicortical position screws bilaterally and elastics; the wire fixation subjects received inferior border wires and 6 weeks of skeletal maxillomandibular fixation with 24-gauge wires. Cephalometric films were obtained before surgery, and at 1 week, 8 weeks, 6 months, 1 year, and 2 years after surgery. Skeletal and dental changes were analyzed using the Johnston's analysis. Before surgery both groups were balanced with respect to linear and angular measurements of craniofacial morphology. Mean anterior advancement of the mandibular symphasis was 5.5 mm (SD, 3.2) in the rigid group and 5.6 mm (SD, 3.0) in the wire group. Two years after surgery, mandibular symphasis was unchanged in the rigid group, whereas the wire group had 26% of sagittal relapse. Dental compensation occurred to maintain the corrected occlusion, with the mandibular incisor moving forward in the wire group and posteriorly in the rigid group. However, at 2 years after surgery, when most subjects were without braces, the overjet and molar discrepancy had relapsed similarly in both groups.

Adolescent↗

PubMed2000

HET/SAF-B overexpression causes growth arrest and multinuclearity and is associated with aneuploidy in human breast cancer.

HET/SAF-B was originally cloned as a nuclear matrix protein that bound to matrix attachment regions and as a transcriptional repressor of the small heat shock protein hsp27. In addition, we have found recently that HET/SAF-B is also a corepressor of estrogen receptor activity. Estrogen receptor has a very well-described role in breast cancer, and aberrant expression of nuclear matrix and heat shock proteins has also been implicated in breast tumorigenesis. Therefore, we asked whether HET/SAF-B itself could be important in breast cancer. Toward this goal we examined its expression in breast cancer cell lines and asked whether HET/SAF-B can affect breast cancer cell proliferation. Finally, we studied HET/SAF-B expression in clinical breast cancer samples. HET/SAF-B protein and mRNA were detected at varying levels in all of the eight breast cancer cell lines examined. Using a number of different approaches to modulate the level of HET/SAF-B protein in the cell, we found that HET/SAF-B levels are inversely correlated with cell proliferation. In addition,transfection of HET/SAF-B fused to the green fluorescent protein led to the formation of multinucleated cells not observed in cells transfected with green fluorescent protein alone, suggesting that this effect is a direct result of HET/SAF-B overexpression. Western blot analysis of HET/SAF-B in 61 human breast tumors revealed widely varying levels of HET/SAF-B expression, with some tumors (16%) lacking any detectable HET/SAF-B. Statistical analysis showed that high HET/SAF-B expression in these tumors was associated with low S-phase fraction and with aneuploidy, consistent with our results from transfection experiments in tissue culture cells. We conclude that HET/SAF-B plays an important role in breast cancer, and we discuss possible mechanisms of the involvement of HET/SAF-B in cell proliferation and division.

3T3 Cells↗

PubMed1999

Loss of heterozygosity at D14S62 and metastatic potential of breast cancer.

BACKGROUND: In breast cancer progression, the prevalence of damage at specific genetic loci often increases with the stage of the lesion (i.e., from noninvasive to invasive to metastatic). By use of genetic markers and analysis of allelic imbalances (loss of heterozygosity [LOH]) to compare DNA samples from paired normal and breast tumor tissues, we examined whether specific genetic changes in primary breast cancers can serve as biomarkers of metastatic potential. METHODS: DNA samples from 76 patients with primary breast cancer (42 with axillary lymph node-negative disease and 34 with axillary lymph node-positive disease) were genotyped with four genetic markers spanning chromosome 14q31-q32. The intensity ratios of the two genetic alleles in normal-tumor DNA pairs were examined in genetically informative individuals. LOH was scored when the tumor allele intensity ratio (tumor allele 1/tumor allele 2) divided by the normal allele intensity ratio (normal allele 1/normal allele 2) was either less than 0.71 (tumor allele 1 LOH) or greater than 1. 4 (tumor allele 2 LOH). RESULTS/CONCLUSIONS: Contrary to our expectations, we found statistically significantly more LOH events at markers D14S62 (two-sided P =.001) and D14S51 (two-sided P =.02) in primary breast cancers from patients with lymph node-negative disease versus lymph node-positive disease, suggesting the presence of a gene in this region that affects metastatic potential. Analysis of small interstitial or terminal deletions in the tumors of six especially informative patients with lymph node-negative disease places the putative metastasis-related gene in a 1490-kilobase region near D14S62. IMPLICATIONS: LOH in the D14S62 region may impede the process of metastasis. Therefore, the D14S62 region LOH profile may have prognostic implications, and the isolation of the metastasis-related gene(s) in this region may lead to better diagnosis and treatment of breast cancer.

Biomarkers, Tumor↗

PubMed1999

Analysis of integrate-and-fire neurons: synchronization of synaptic input and spike output.

A new technique for analyzing the probability distribution of output spikes for the integrate-and-fire model is presented. This technique enables us to investigate models with arbitrary synaptic response functions that incorporate both leakage across the membrane and a rise time of the postsynaptic potential. The results, which are compared with numerical simulations, are exact in the limit of a large number of small-amplitude inputs. This method is applied to the synchronization problem, in which we examine the relationship between the spread in arrival times of the inputs (the temporal jitter of the synaptic input) and the resultant spread in the times at which the output spikes are generated (output jitter). The results of previous studies, which indicated that the ration of the output jitter to the input jitter is consistently less than one and that it decreases for increasing numbers of inputs, are confirmed for three classes of the integrate-and-fire model. In addition to the previously identified factors of axonal propagation times and synaptic jitter, we identify the variation in the spike-generating thresholds of the neurons and the variation in the number of active inputs as being important factors that determine the timing jitter in layered networks. Previously observed phase differences between optimally and suboptimally stimulated neurons may be understood in terms of the relative time taken to reach threshold.

Action Potentials↗

PubMed1999

Condylar position with rigid fixation versus wire osteosynthesis of a sagittal split advancement.

PURPOSE: In this randomized clinical study, two groups of patients who underwent a bilateral sagittal split osteotomy and either wire osteosynthesis or rigid fixation were compared. PATIENTS AND METHODS: Cephalometric radiographs obtained before surgery, immediately after surgery, and at 8 weeks, 6 months, and 1 and 2 years after surgery were available for 125 of these patients, 63 with wire fixation and 62 with rigid fixation. All were traced by an independent examiner, and vertical and horizontal changes in condylar position were recorded for each period. RESULTS: Condylar movement was slightly different with the two fixation techniques beyond 8 weeks postsurgery, but the ultimate position of the condyle was not different. The condyles in both groups moved posterior and superior. There initially was a correlation between the amount of advancement and the amount the condyle moved inferior in both groups, but this diminished with time. In addition, there was a weak but significant positive relationship between forward rotation of the proximal segment and superior condylar position immediately after surgery, which did not exist at later periods. CONCLUSIONS: Whether wire osteosynthesis or rigid fixation was used, the ultimate condylar position was posterior and superior after a bilateral sagittal split osteotomy to advance the mandible. No single factor could be identified to account for this change. It is suggested that change in mechanical load may have resulted in remodeling and adaptation of the condyles.

Adolescent↗

PubMed1999

The neurotrophins act synergistically with LIF and members of the TGF-beta superfamily to promote the survival of spiral ganglia neurons in vitro.

A number of growth factor families have been implicated in normal inner ear development, auditory neuron survival and protection. Several growth factors, including transforming growth factor-beta5 (TGF-beta5) and TGF-beta3, neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF) and leukemia inhibitory factor (LIF) were tested for their ability, individually or in combination, to promote auditory neuron survival in dissociated cell cultures of early rat post-natal spiral ganglion cells (SGCs). The results indicate that at discrete concentrations all growth factors act in an additive fashion and some in synergy when promoting neuronal survival. These findings support the hypothesis that growth factors from different families may be interdependent when sustaining neuronal integrity.

Animals↗

PubMed1999

Psychological function in orthognathic surgical patients before and after bilateral sagittal split osteotomy with rigid and wire fixation.

A multisite randomized controlled trial was conducted to compare the psychological function of patients who undergo surgical correction of a Class II malrelation with bilateral sagittal split osteotomy with either wire or rigid fixation. Subjects were 31 male and 86 female patients referred by orthodontists. Psychopathological symptoms and psychological distress were measured with the Symptom Checklist-90 Revised at the following times: before placement of orthodontic appliances, 1 to 2 weeks presurgery, and 1 week, 8 weeks, 6 months, and 2 years postsurgery. Patients' satisfaction with their surgical outcome was measured with a 3-item questionnaire. Results showed no statistically significant differences in psychological function or satisfaction between patients treated with wire or rigid fixation. Psychological function was within normal limits immediately before surgery. Psychological parameters did not determine patient satisfaction, even among patients who met an operational definition of "psychopathological caseness." Psychological symptoms and general distress increased modestly immediately after surgery for both groups and then progressively declined over the succeeding 2 years, eventually reaching levels that were significantly lower than presurgical levels. It was concluded that (1) rigid and wire fixation do not differ in their effects on psychological function and satisfaction; (2) patients who seek orthognathic surgery for a Class II malocclusion are psychologically healthy, ie, comparable to normal populations, immediately before surgery; (3) presurgical psychological function does not determine satisfaction with surgical outcome; and (4) psychological function tends to improve during the 2 years after surgery.

Adult↗

PubMed1999

Enhanced prediction of breast cancer prognosis by evaluating expression of p53 and prostate-specific antigen in combination.

p53 gene mutation is the most common genetic alteration in neoplastic diseases, including breast cancer, for which p53 alteration may indicate poor prognosis. Recent clinical evidence suggests that prostate-specific antigen (PSA) expression may identify breast cancer patients with favourable outcome. Assessment of p53 and PSA in combination, potentially offering improved prediction, has not yet been performed. Extracts from 952 primary breast carcinomas were assayed for PSA and p53 by quantitative enzyme-linked immunosorbent assays (ELISAs) developed by the authors. Concentrations of each marker were classified as negative or positive on the basis of median and 30th percentile cut-off points for p53 and PSA respectively. Patients followed for a median of 6 years having different combinations of negative or positive status for PSA and p53 were compared with respect to the relative risks (RRs) for relapse and death by Cox proportional hazards regression analysis, in which an interaction term was also evaluated, and with respect to disease-free survival (DFS) and overall survival (OS) probabilities by Kaplan-Meier plots and log-rank tests. Multivariate models were adjusted for oestrogen and progesterone receptor status, nodal status, patient age, tumour size, DNA ploidy, S phase fraction and receipt of chemotherapy. Interactions were not found between the status of PSA and p53 in the Cox models, in which PSA-negativity (RR = 1.47, P = 0.020 for DFS, and RR = 1.49, P = 0.023 for OS) and p53-positivity (RR = 1.46, P = 0.017 for DFS, and RR = 1.41, P = 0.033 for OS) were individually associated with prognosis. Evaluation of a combined three-level variable revealed that PSA(-)/p53(+) patients had significantly higher risks for relapse (RR = 2.13, P < 0.001) and death (RR = 2.08, P = 0.001) than PSA(+)/p53(-) patients, and that patients positive or negative for both markers had intermediate risks for the outcome events in the same multivariate analysis (RR = 1.45 for both DFS and OS). The results of our study demonstrate that the assessment of combined PSA and p53 expression status by ELISAs, easily applicable to breast tumour extracts prepared for steroid hormone receptor analyses, may stratify breast cancer patients into groups differing by relapse and death risks of greater magnitude than offered by the assessment of either p53 or PSA alone.

Age Factors↗

PubMed1999

Chronic electrical stimulation of the auditory nerve using non-charge-balanced stimuli.

This study was designed to evaluate the pathophysiological response of the cochlea following long-term intracochlear electrical stimulation using a poorly charge-balanced stimulus regime, leading to direct current (DC) levels >0.1 microA. Four normal-hearing adult cats were bilaterally implanted with scala tympani electrode arrays and unilaterally stimulated for periods up to 2200 h. Stimuli consisted of 50 micros monophasic current pulses presented at 2000 pulses per second (pps) per channel, and resulted in DC levels of 0.4-2.8 microA. Both acoustic and electrical (EABR) evoked potentials were periodically recorded during the stimulation program. Frequency-specific stimuli indicated that an extensive and widespread hearing loss occurred over the 4-24 KHz region in all stimulated cochleae, although the 2 KHz region exhibited thresholds close to normal in some animals, despite long-term implantation and chronic stimulation. Longitudinal EABRs showed a statistically significant increase in threshold for three of the four animals. Histopathological evaluation of the cochleae revealed a highly significant reduction in ganglion cell density in stimulated cochleae compared with their controls. Spiral ganglion cell loss was significantly correlated with the degree of inflammation, duration of electrical stimulation, and the level of DC. In conclusion, the present study highlights the potential for neural damage following stimulation using poorly charge-balanced stimuli.

Action Potentials↗