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Biomedical subjects

G M Clark

Publications and source records attributed to G M Clark.

At least 307 records · Page 17Linked to original sources

Treatment decisions in axillary node-negative breast cancer patients.

Treatment decisions must be made on 9000 axillary node-negative breast cancer patients each month in the United States. Which of these patients will benefit from adjuvant therapy is a major question. Valid methods are needed to distinguish those patients who are "cured" from those who will suffer a cancer recurrence. A complex network of prognostic variables enters into the treatment decision, together with a risk-versus-benefit assessment. We are using a neural-network-based form of artificial intelligence that, once "trained" with data representing an event and its outcome, can identify subsets of patients with low recurrence risks. Larger data sets are being evaluated with the hope of introducing the neural-network technique to routine clinical practice.

Breast Neoplasms↗

Human cochlear nucleus: comparison of Nissl-stained neurons from deaf and hearing patients.

In this study of the effects of deafness on the morphology of the human cochlear nuclei, non-parametric statistical analysis is used to quantify differences in sizes and shapes of neuron somata. Data on 81,007 neuron somata from 11 patients are presented, as well as the total volume and surface area of the cochlear nuclei. Soma size of deaf patients, especially postlinguistically deaf ones, was smaller than that of controls, but not significantly so; the same was true for total cochlear nucleus volume. The data also indicate a greater soma size on the right side (as well as a greater ventral cochlear nucleus volume), a caudal-to-rostral decrease in soma size, and a correlation between soma size and shape. The data base is being continually extended and in future will allow comparisons with measurements from patients suffering from various forms of hearing loss.

Aged↗

Follow-up study of HER-2/neu amplification in primary breast cancer.

Amplification of the HER-2/neu oncogene was determined in 362 tumors from patients with primary breast cancer (185 node-positive patients and 177 node-negative patients). The overall amplification rate was 33% (30% for node-negative patients; 31% for patients with 1-3 positive nodes; 40% for patients with greater than 3 positive nodes). Gene copy number was not associated with axillary lymph node status, steroid receptor status, or patient age but was weakly correlated with the size of the primary tumor. Amplification of the HER-2/neu gene did not correlate with either disease-free or overall survival in univariate or multivariate analyses. The results were unambiguously negative for patients with node-negative disease. Although the univariate results for node-positive patients were marginally significant (P = 0.07), the significance was not retained in multivariate analyses. Thus, while HER-2/neu amplification may be biologically important in primary breast cancer, it will only be of marginal utility as a prognostic factor for predicting clinical outcome.

Breast Neoplasms↗

Scanning electron microscopy of platinum scala tympani electrodes following chronic stimulation in patients.

Platinum (Pt) electrodes from three auditory prostheses (Cochlear Pty Ltd) were examined for evidence of corrosion following implantation periods of up to 1000 days. These devices were used for periods ranging from 1600 to 10,400 h and developed maximum charge densities of 0.257 microC mm-2 geom. per phase. Scanning electron microscopy of the surface of the 66 stimulated electrodes examined showed no evidence of definitive Pt corrosion. Their surface features were essentially identical to control (unstimulated) electrodes. In addition, there was no evidence of any change in the surface morphology of the Silastic carrier adjacent to the stimulating electrodes. These results indicate that Pt is a suitable electrode material for neural prostheses that use relatively large surface area electrodes (0.1-1.0 mm2) and low to moderate charge densities (0.01-0.26 microC mm-2 geom. per phase).

Biocompatible Materials↗

Electrical stimulation of the auditory nerve in deaf kittens: effects on cochlear nucleus morphology.

The present study examines the effects of long-term electrical stimulation of the auditory nerve on the morphology of neurons in the cochlear nucleus in young, sensorineural deaf animals. Kittens, systemically deafened using kanamycin and ethacrynic acid, received bilateral cochlear implants and were stimulated unilaterally for periods of up to four months. After sacrifice, cross-sectional areas of neuron somata were measured with an image-analysis system and compared using nonparametric statistics. The areas of cell somata within the anteroventral cochlear nucleus (AVCN) on the stimulated side were significantly larger than those of corresponding somata on the control, unstimulated side (P less than 0.001). However, there was no statistically significant difference among dorsal cochlear nucleus (DCN) neurons. These results indicate that long-term electrical stimulation of the auditory nerve can at least partially negate some effects of early postnatal auditory deprivation at the level of the cochlear nucleus.

Animals↗

Association of INT2/HST1 coamplification in primary breast cancer with hormone-dependent phenotype and poor prognosis.

The human proto-oncogene INT2 (homologous to the mouse INT2 gene, implicated in proviral induced mammary carcinoma) has been mapped to chromosome 11q13 and found to share band localisation with, among others, the HST1 proto-oncogene. Both genes are members of the fibroblast growth factor family. In the present study, coamplification (2-15 copies) of the INT2/HST1 genes was found in 27 (9%) of 311 invasive human breast carcinomas using slot blot and Southern blot analyses. Amplification was not correlated to tumour size, axillary lymph node status or stage of disease, neither to patient age nor menopausal status. However, 26 (96%) of the 27 amplified tumours were, often strongly, Oestrogen receptor positive compared to 65% of the unamplified cases (P = 0.001). These findings are in sharp contrast to the strong correlations of HER-2/neu proto-oncogene amplification with advanced stage and steroid receptor negativity, previously observed in the same series of tumours. Patients with INT2/HST1 amplified breast cancer had a significantly shorter disease-free survival compared to those with unamplified genes (P = 0.015, median follow up 45 months). This correlation was confined to node-negative patients and persisted in multivariate analysis. No significant correlation to survival from breast cancer was found. It is concluded that amplification of the 11q13 region in breast cancer occurs in a particular subset of aggressive tumours, quite different from that identified by HER-2/neu amplification. It still remains to be shown that the selection for amplified genes at 11q13 is due to the activity of INT2, HST1 or yet another, still unidentified, neighbouring gene. However, the results are potentially of clinical value in separating a group of node-negative breast cancer for more intense treatment.

Adult↗

Role of a multichannel electrotactile speech processor in a cochlear implant program for profoundly hearing-impaired adults.

Four profoundly hearing-impaired adults who did not meet current selection criteria for implantation at the University of Melbourne were each fitted with a wearable multichannel electrotactile speech processor (Tickle Talker). The subjects were evaluated with a test battery of speech discrimination tests subsequent to training in use of the device. Thresholds for detection of pure tones were lower for the Tickle Talker than for hearing aids across the frequency range 250 to 4000 Hz. Mean speech detection thresholds for the Ling 5-sound test showed that all sounds were detected by users of the electrotactile device at normal conversational speech intensity levels. Mean speech discrimination scores were significantly higher (p less than 0.05) in the tactually aided condition as compared with the tactually unaided for identification of vowels and consonants, on open-set words, open-set sentences, and on connected discourse tracking. Mean scores increased by 20% for vowels, 19% for consonants, 30% for open-set words, and 25% for open-set sentences when the Tickle Talker was used in a multimodal combination with lipreading or lipreading and hearing aids. Speechtracking rates for three subjects showed increases of from 18 to 28 wpm when the tactile device was used. Comparison of tactually aided versus unaided tracking rates for two subjects with long-term experience shows continuing improvement with additional experience with the device. These results demonstrate that hearing-impaired adults not meeting selection criteria for cochlear implantation may benefit from use of an electrotactile speech processor, and highlight the potential benefits from integration of such devices into cochlear implant programs for profoundly hearing-impaired patients.

Acoustics↗

The Nucleus 22-channel cochlear implant system.

Cochlear implants have become the treatment of choice for profoundly deaf adults and children who obtain little or no benefit from conventional amplification. Sounds are translated into small electric currents that stimulate the auditory nerves in the cochlea and generate hearing sensations. The Nucleus cochlear implant is the result of more than 20 yr of research and development, first at the University of Melbourne, Australia and later by Cochlear Proprietary Limited (Sydney, Australia) in collaboration with the University of Melbourne. Today, the cochlear Mini-22 implant system is approved by the United States Food and Drug Administration (FDA) for use in adults and children, and has been implanted in more than 3000 patients worldwide. Although this chapter describes the cochlear implant system and clinical issues related to its use in children, much of the material has been derived from experience with adults. Furthermore, the Nucleus system is not static. It is being continually improved both in performance and ease of use. The purpose of this chapter is to describe developments leading up to and including the present Nucleus cochlear implant system. Other chapters in this issue present results and procedures relating to pediatric applications of the device.

Adult↗

Perception of multiple electrode stimulus patterns: implications for design of an electrotactile speech processor.

Identification of multiple-electrode stimulus patterns was evaluated in nine adult subjects, to assess the feasibility of providing additional speech information through the tactual display of an electrotactile speech processor. Absolute identification scores decreased from 97.8% for single electrodes, to 61.9% for electrode pairs, and, to 31.8% for electrode triplets. Although input information increased with paired-and triple-electrode stimuli, information transmission scores were not significantly increased for either electrode pairs (2.99 bits) or triplets (2.84 bits) as compared with single electrodes (2.84 bits). These results suggest that speech coding strategies using stimulus patterns of electrode pairs or triplets would provide little improvement beyond that found for the present single-electrode scheme. However, higher absolute identification scores (73.6%), and an increase in information transmission to 3.88 bits, were recorded for test stimuli containing all combinations of paired and single electrodes. Based on this finding, two stimulus sets using a restricted number of combinations of paired and single electrodes were evaluated. The two stimulus sets simulated the spatial patterns of paired and single electrodes arising from use of alternative speech coding schemes to increase consonant voicing information. Results for the two stimulus sets showed higher electrode identification scores (79.7% and 90.4%), as compared with paired-electrode stimuli. Although electrode identification score was not as high as for single electrodes, information transmission was increased to 3.31 bits for the VF2 stimulus set. Analysis of the responses also showed that scores for identification of simulated voicing information conveyed by the two stimulus sets were 99.4 and 90.4% correct.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A comparison of steady-state evoked potentials to modulated tones in awake and sleeping humans.

Steady-state evoked potential responses were measured to binaural amplitude-modulated (AM) and combined amplitude- and frequency-modulated (AM/FM) tones. For awake subjects, AM/FM tones produced larger amplitude responses than did AM tones. Awake and sleeping responses to 30-dB HL AM/FM tones were compared. Response amplitudes were lower during sleep and the extent to which they differed from awake amplitudes was dependent on both carrier and modulation frequencies. Background EEG noise at the stimulus modulation frequency was also reduced during sleep and varied with modulation frequency. A detection efficiency function was used to indicate the modulation frequencies likely to be most suitable for electrical estimation of behavioral threshold. In awake subjects, for all carrier frequencies tested, detection efficiency was highest at a modulation frequency of 45 Hz. In sleeping subjects, the modulation frequency regions of highest efficiency varied with carrier frequency. For carrier frequencies of 250 Hz, 500 Hz, and 1 kHz, the highest efficiencies were found in two modulation frequency regions centered on 45 and 90 Hz. For 2 and 4 kHz, the highest efficiencies were at modulation frequencies above 70 Hz. Sleep stage affected both response amplitude and background EEG noise in a manner that depended on modulation frequency. The results of this study suggest that, for sleeping subjects, modulation frequencies above 70 Hz may be best when using steady-state potentials for hearing threshold estimation.

Acoustics↗

Surgical complications with the cochlear multiple-channel intracochlear implant: experience at Hannover and Melbourne.

The surgical complications for the first 153 multiple-channel cochlear implant operations carried out at the Medizinische Hochschule in Hannover and the first 100 operations at the University of Melbourne Clinic, The Royal Victorian Eye and Ear Hospital, are presented. In the Hannover experience the major complications were wound breakdown, wound infection, electrode tie erosion through the external auditory canal, electrode slippage, a persistent increase in tinnitus, and facial nerve stimulation. The incidence of wound breakdown requiring removal of the package was 0.6% in Hannover and 1.0% in Melbourne. The complications for the operation at both clinics were at acceptable levels. It was considered that wound breakdown requiring implant removal could be kept to a minimum by making a generous incision and suturing the flap without tension.

Australia↗

Cochlear pathology following chronic electrical stimulation using non charge balanced stimuli.

During the course of a chronic intracochlear electrical stimulation study using charge balanced biphasic current pulses, one animal inadvertently received a short period of direct current (DC) stimulation at a level of approximately 1 microA. Subsequent, the animal was chronically stimulated using a poorly charge balanced waveform that produced a DC level of approximately 2 microA. Extensive pathological changes were observed within the cochlea. These changes included widespread spiral ganglion cell loss and new bone growth that extended throughout all turns of the cochlea. Significant changes in the morphology of the electrically evoked auditory brainstem response (EABR) were associated with these pathological changes. EABRs recorded prior to the DC stimulation exhibited a normal waveform morphology. However, responses recorded during the course of the DC stimulation were dominated by a short latency response believed to be vestibular in origin. The response thresholds were also significantly higher than levels recorded before the DC stimulation. In contrast, the contralateral cochlea, stimulated using charge balanced stimuli, showed no evidence of adverse pathological changes. Furthermore, EABRs evoked from this cochlea remained stable throughout the chronic stimulation period. Although preliminary, the present results illustrate the adverse nature of poorly charge balanced electrical stimuli. These results have important implications for both the design of neural prostheses and the use of DC stimuli to suppress tinnitus in patients.

Animals↗

Results of speech perception and speech production training for three prelingually deaf patients using a multiple-electrode cochlear implant.

Five studies were conducted to measure changes in the perception and production of selected speech targets, with training, in three prelingually deaf patients. The two adults and one adolescent were implanted with the Cochlear (Nucleus) multiple-electrode prosthesis. The studies were perception and production of nasal consonants; perception of syllable-final consonants; perception and production of alveolar consonants; auditory-visual perception of alveolar consonants; and perception and production of vowels. Perceptual data were collected in the audition (implant)-alone condition, except for the auditory-visual perception of alveolar consonants where the audition-alone, vision-alone, and auditory-visual conditions were used. Speech perception data in the audition-alone condition were also collected from four postlingually deaf adult implant patients, without training, to indicate differences between the two classes of patients. The three prelingually deaf patients generally showed some improvements in speech production. In perception, improvements were recorded only for individual patients in some studies. The performance of the adolescent was better than that of the two adults in all cases. The perceptual performance of the postlingually deaf patients was superior to that of the prelingually deaf patients in all cases.

Adolescent↗

Use of a multichannel electrotactile speech processor by profoundly hearing-impaired children in a total communication environment.

As part of a larger subject group, four profoundly hearing-impaired children enrolled in a total communication educational program were fitted with the University of Melbourne's multichannel electrotactile speech processor (Tickle Talker). Sound detection thresholds for pure tones were at lower levels with the tactile device than with hearing aids, especially for high frequency sounds above 2 kHz. Two of the children also detected all speech sounds of the Ling five-sound test at normal conversational levels using only the Tickle Talker. The children were able to use tactile input to achieve higher scores on three speech feature subtests of the PLOTT test when using the Tickle Talker plus hearing aids as compared to hearing aids alone. Mean improvements were 22.4 percent on vowel length, 28 percent on vowel identification, and 35 percent on consonant manner. Improvements were also shown by individual children on the closed-set WIPI and open-set PBK word tests, and on the open-set BKB sentence test, when the Tickle Talker was combined with hearing aids, and with hearing aids and lipreading. Comparisons of these results with those of children using the Tickle Talker in other educational settings show that children in a total communication environment can potentially benefit to a similar degree from use of tactual input. Anecdotal reports from the children and school staff members indicated that daily use of the Tickle Talker did not interfere with the signing aspects of total communication.

Adolescent↗