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Biomedical subjects

G M Clark

Publications and source records attributed to G M Clark.

At least 325 records · Page 18Linked to original sources
PubMed1991

Multichannel cochlear implantation in children: a summary of current work at the University of Melbourne.

This paper summarizes research work relating to multichannel cochlear implantation in children at the University of Melbourne. Ongoing safety studies relating to the implantation of young children are discussed. Results of these studies suggest that special design considerations are necessary for a prosthesis to be implanted in children under the age of 2 years. Results of clinical assessment of implanted children and adolescents are also discussed in terms of speech perception, speech production, and language development, and some possible predictive factors are suggested. Preliminary data suggests that a high proportion of young children can achieve open-set speech perception with the cochlear implant given appropriate training and support. Initial results with adults using new speech processing hardware and a new coding scheme are also presented. These suggest that improved speech perception in quiet and competing noise is possible with the new system.

Adolescent↗
PubMed1990

HER-2/neu amplification predicts poor survival in node-positive breast cancer.

HER-2/neu protooncogene amplification and protein expression were analyzed with slot blot and Western blot techniques, respectively, in more than 300 invasive primary breast tumors of all stages. Amplification (2- greater than 30 copies) was found in 17% of these tumors and high expression was seen in 19%. There was a striking coincidence between gene amplification and high expression. Tumors associated with many involved axillary lymph nodes or with Stage IV disease were more often HER-2/neu amplified or overexpressed. Furthermore, gene alteration was strongly correlated with the absence of steroid receptors and with larger tumor size. High expression without gene amplification was seen in a minor subset of tumors of less aggressive character. Neither amplification nor overexpression was correlated with disease outcome for patients with negative axillary lymph nodes. For node-positive patients, however, HER-2/neu amplification was a significant predictor of early relapse and death (median follow-up = 45 months), and a similar trend, although not significant, existed for high gene expression. Multivariate analyses indicated that HER-2/neu alterations were not independent predictors of patient outcome.

Amino Acid Sequence↗
PubMed1990

Association of the 323/A3 surface glycoprotein with tumor characteristics and behavior in human breast cancer.

We have earlier described a monoclonal antibody (323/A3) against a Mr 43,000 surface glycoprotein of MCF-7 human breast cancer cells which shows considerable specificity for primary and metastatic breast tumors (Cancer Res., 46: 1306-1317, 1986). Here we report the occurrence of the 323/A3 antigen in a large cohort of primary breast tumors (m = 384) and its interrelationship with several clinically important variables. Frozen, stored tumor tissues were examined by a Western blot procedure, and the level of 323/A3 protein in individual tumors was calculated in arbitrary units based on the integrated Mr 43,000 signal in tumors compared with an MCF-7 internal standard. Thirty-six % (139 of 384) of tumors were found to be positive for 323/A3. Higher frequencies of 323/A3 protein were found in tumors larger than 2 cm (P = 0.03), tumors with infiltrated lymph nodes (P = 0.01), and tumors without estrogen receptor (P = 0.006). No significant relationship was found with patient age, menopausal status, or progesterone receptor status. Of the newer clinical determinants proliferative rate (% S phase), DNA ploidy, and the lysosomal protease cathepsin D, but not the HER-2/neu oncogene protein, were significantly correlated with 323/A3. The presence of 323/A3 protein was also related to increased recurrence (P = 0.003) and mortality (P = 0.036) after primary treatment. As an exposed surface antigen, this glycoprotein might be a useful target in radioimaging and immunotherapy of some human breast tumors, especially those having large size, infiltrated lymph nodes, deficient estrogen receptor, high proliferative rate, abnormal DNA content, and high levels of cathepsin D, all of which are ominous indicators of tumor behavior.

Adult↗
PubMed1990

Cathepsin D and prognosis in breast cancer.

We investigated the possibility that cathepsin D, an estrogen-induced lysosomal protease, might have value as a prognostic factor in breast cancer by studying frozen tissue specimens from 397 patients. We measured the 34-kd mature form of the enzyme by Western blot assay and densitometry. Among 199 patients with node-negative disease, but not among 198 with node-positive disease, high levels of cathepsin D proved to be a significant predictor of reduced disease-free survival (median follow-up, 64 months), either as a continuous variable (log cathepsin D; P = 0.018) or as a dichotomous variable with an optimized cutoff point (P = 0.0001). Results were similar for overall survival (P = 0.009 and 0.0001, respectively). Relating the level of cathepsin D to other prognostic factors in the patients with node-negative disease, we found an association with aneuploidy but none with estrogen or progesterone receptors, tumor size, or the age of the patient. In multivariate analyses, a high level of cathepsin D was the most important independent factor in predicting shorter disease-free and overall survival in patients with node-negative disease. As compared with the risk in women with low levels of cathepsin D, the relative risk of tumor recurrence was 2.6 (95 percent confidence interval, 1.6 to 4.4) and the relative risk of death was 3.9 (95 percent confidence interval, 2.1 to 7.3) among those with high levels of cathepsin D. For disease-free survival, cathepsin D status was predictive of outcome primarily among those with aneuploid tumors; the actuarial five-year recurrence rates of aneuploid tumors were 60 percent among women with high levels of cathepsin D and 29 percent among those with low levels, as compared with 22 percent for all diploid tumors. We conclude that cathepsin D may be an independent predictor of early recurrence and death in node-negative breast cancer.

Biomarkers, Tumor↗
PubMed1990

Selection of cancer chemotherapy for a patient by an in vitro assay versus a clinician.

One hundred thirty-three patients with advanced metastatic cancer were randomized to receive single-agent chemotherapy selected by either a medical oncologist or an in vitro capillary cloning system. Thirty-six of the 65 patients (55%) who were randomly assigned to selection of a drug by the clinician actually received a drug; these patients were able to be evaluated for clinical response. Of these 36 patients, one had a partial tumor response (3%). Only 19 of the 68 patients (28%) who were randomly assigned to selection of a drug by the capillary system actually received a drug; these patients were able to be evaluated for clinical response. Of these 19 patients, four (21%) had partial tumor responses. In the assessable patients (36 in the clinician's choice group, 19 in the capillary cloning group), the partial response rate was superior for drug selection by the capillary cloning system (P = .04). For all patients randomly assigned to a group (65 in the clinician's choice group, 68 in the capillary cloning group), the response rate was not significantly different (1.5% and 5.9%, respectively; P = .37). When overall survival rates for patients in the two groups were compared, there was no difference. We conclude that drug sensitivity testing in capillary tubes can improve the response rate for patients with advanced malignancies. This improved response rate, however, does not translate into improved survival times for these patients.

Antineoplastic Agents↗
PubMed1990

A comparison of two training strategies for speech recognition with an electrotactile speech processor.

Seven normally hearing adults were trained in the use of a multiple-channel electrotactile speech processor for 70 hours over a 6-month period. Two training strategies were used on each of the subjects: (1) analytic-plus-synthetic (AS), and (2) synthetic (S). The speech perception abilities of the subjects were assessed with closed sets of vowels and consonants, open sets of words and sentences, and speech tracking, for the tactile-plus-lipreading, tactile, and lipreading conditions. The subjects were tested on three separate occasions: (1) at the beginning of the study, (2) after 35 hours of training, and (3) after a further 35 hours of training. Wilcoxon matched-pair signed-ranks (MPSR) tests showed that improvements observed with both the AS and S strategies were significantly (p less than .05) greater than zero for most tests and conditions. The Wilcoxon MPSR test showed that the difference in improvements between the training strategies was significant for only the vowel and consonant tests in the tactile condition.

Adolescent↗
PubMed1990

Testosterone, sex hormone-binding globulin, calculated free testosterone, and oestradiol in male vegans and omnivores.

Total testosterone (T), total oestradiol (E2) and sex hormone-binding globulin (SHBG) concentrations were measured in plasma samples from fifty-one male vegans and fifty-seven omnivores of similar age. Free T concentration was estimated by calculation. In comparison with the omnivores, the vegans had 7% higher total T (P = 0.250), 23% higher SHBG (P = 0.001), 3% lower free T (P = 0.580), and 11% higher E2 (P = 0.194). In a subset of eighteen vegans and twenty-two omnivores for whom 4 d diet records were available, there were statistically significant correlations between T and polyunsaturated fatty acids (r 0.37), SHBG and fat (r 0.43 for total fat, 0.46 for saturated fatty acids and 0.33 for polyunsaturated fatty acids), and SHBG and alcohol (r-0.39). It is concluded that a vegan diet causes a substantial increase in SHBG but has little effect on total or free T or on E2.

Adult↗
PubMed1990

Speech feature recognition by profoundly hearing impaired children using a multiple-channel electrotactile speech processor and aided residual hearing.

A group of prelinguistically hearing impaired children, between 7 and 11 years of age, were trained in the perception of vowel duration and place, the fricative /s/, and manner of articulation (/m/ vs /b/ and /s/ vs /t/) distinctions, using information provided by a multiple-channel electrotactile aid (Tickle Talker), and through aided hearing. Training was provided in the tactile-plus-aided hearing (TA) and tactile (T) conditions. Speech feature recognition tests were conducted in the TA, T, and aided hearing (A) conditions, during pretraining, training, and post-training phases. Test scores in the TA and T conditions were significantly greater than scores in the A condition for all tests, suggesting that perception of these features was improved when the tactile aid was worn. Test scores in the training and post-training phases were significantly greater than in the pretraining phase, suggesting that the training provided was responsible for the improvement in feature perception. Statistical analyses demonstrated a significant interaction between the main effects of condition and phase, suggesting that training improved perception in the TA and T conditions, but not in the A condition. Post-training and training test scores were similar suggesting that the perceptual skills acquired during training were retained after the removal of training. Recognition of trained features improved for trained, as well as for untrained words.

Child↗
PubMed1990

Perception of sentences, words, and speech features by profoundly hearing-impaired children using a multichannel electrotactile speech processor.

Fourteen prelinguistically profoundly hearing-impaired children were fitted with the multichannel electrotactile speech processor (Tickle Talker) developed by Cochlear Pty. Ltd. and the University of Melbourne. Each child participated in an ongoing training and evaluation program, which included measures of speech perception and production. Results of speech perception testing demonstrate clear benefits for children fitted with the device. Thresholds for detection of pure tones were lower for the Tickle Talker than for hearing aids across the frequency range 250-4000 Hz, with the greatest tactual advantage in the high-frequency consonant range (above 2000 Hz). Individual and mean speech detection thresholds for the Ling 5-sound test confirmed that speech sounds were detected by the electrotactile device at levels consistent with normal conversational speech. Results for three speech feature tests showed significant improvement when the Tickle Talker was used in combination with hearing aids (TA) as compared with hearing aids along (A). Mean scores in the TA condition increased by 11% for vowel duration, 20% for vowel formant, and 25% for consonant manner as compared with hearing aids alone. Mean TA score on a closed-set word test (WIPI) was 48%, as compared with 32% for hearing aids alone. Similarly, mean WIPI score for the combination of Tickle Talker, lipreading, and hearing aids (TLA) increased by 6% as compared with combined lipreading and hearing aid (LA) scores. Mean scores on open-set sentences (BKB) showed a significant increase of 21% for the tactually aided condition (TLA) as compared with unaided (LA). These results indicate that, given sufficient training, children can utilize speech feature information provided through the Tickle Talker to improve discrimination of words and sentences. These results indicate that, given sufficient training, children can utilize speech feature information provided through the Tickle Talker to improve discrimination of words and sentences. These results are consistent with improvement in speech discrimination previously reported for normally hearing and hearing-impaired adults using the device. Anecdotal evidence also indicates some improvements in speech production for children fitted with the Tickle Talker.

Adolescent↗
PubMed1990

Place coding of vowel formants for cochlear implant patients.

Four multiple-channel cochlear implant patients were tested with synthesized versions of the words "hid, head, had, hud, hod, hood" containing 1, 2, or 3 formants, and with a natural 2-formant version of the same words. The formant frequencies were encoded in terms of the positions of electrical stimulation in the cochlea. Loudness, duration, and fundamental frequency were kept fixed within the synthetic stimulus sets. The average recognition scores were 47%, 61%, 62%, and 79% for the synthesized 1-, 2-, and 3-format vowels and the natural vowels, respectively. These scores showed that the place coding of the first and second formant frequencies accounted for a large part of the vowel recognition of cochlear implant patients using these coding schemes. The recognition of the natural stimuli was significantly higher than recognition of the synthetic stimuli, indicating that extra cues such as loudness, duration, and fundamental frequency contributed to recognition of the spoken words.

Attention↗
PubMed1990

Perception of amplitude envelope variations of pulsatile electrotactile stimuli.

Gross variations of the speech amplitude envelope, such as the duration of different segments and the gaps between them, carry information about prosody and some segmental features of vowels and consonants. The amplitude envelope is one parameter encoded by the Tickle Talker, an electrotactile speech processor for the hearing impaired which stimulates the digital nerve bundles with a pulsatile electric current. Psychophysical experiments measuring the duration discrimination and identification, gap detection, and integration times for pulsatile electrical stimulation are described and compared with similar auditory measures for normal and impaired hearing and electrical stimulation via a cochlear implant. The tactile duration limen of 15% for a 300-ms standard was similar to auditory measures. Tactile gap detection thresholds of 9 to 20 ms were larger than for normal-hearing but shorter than for some hearing-impaired listeners and cochlear implant users. The electrotactile integration time of about 250 ms was shorter than previously measured tactile values but longer than auditory integration times. The results indicate that the gross amplitude envelope variations should be conveyed well by the Tickle Talker. Short bursts of low amplitude are the features most likely to be poorly perceived.

Adult↗
PubMed1990

Dimensions of the scala tympani in the human and cat with reference to cochlear implants.

The width, height, and cross-sectional area of the scala tympani in both the human and cat were measured to provide dimensional information relevant to the design of scala tympani electrode arrays. Both the height and width of the human scala tympani decreased rapidly within the first 1.5 mm from the round window. Thereafter, they exhibit a gradual reduction in their dimension with increasing distance from the round window. The cross-sectional area of the human scala tympani reflects the changes observed in both the height and width. In contrast, the cat scala tympani exhibits a rapid decrease in its dimensions over the first 6 to 8 mm from the round window. However, beyond this point the cat scala tympani also exhibits a more gradual decrease in its dimensions. Finally, the width of the scala tympani, in both human and cat, is consistently greater than the height.

Anatomy, Comparative↗
PubMed1990

Perceptual-oral training of two hearing-impaired children in the recognition and production of /s/ and /z/.

Two hearing-impaired children were tested and trained in the utilization of an artificial acoustic cue that signalled the presence of /s/ and /z/ in verbal stimuli. These sounds, chosen because they are among the most important morphemes in English, were both perceived and produced significantly better by the subjects following only seven training sessions when the cue, automatically signalled by a specially designed laboratory device, was presented at a 20 dB sensation level in a frequency range immediately above the subjects' upper limits of hearing for amplified speech. The implications of the study are briefly discussed in relation to testing and training procedures involving sensory aids.

Auditory Threshold↗
PubMed1990

Comparison of two speech processing schemes using normal-hearing subjects.

Two speech processing schemes have been implemented on a real-time laboratory speech processor for speech perception studies on normal-hearing subjects. The first scheme presents the information of two spectral components, the first and second formant of the speech signal, and will be referred to as the ZC (zero-crossing) scheme. The second scheme presents the information of four spectral components, four spectral peaks of the speech signal determined from the output of a filter bank, and will be referred to as the FB (Filter-bank) scheme. Perceptual studies were conducted on 4 normal-hearing subjects. Two of the 4 subjects were first trained and tested using the ZC scheme while the other 2 used the FB scheme. The training and testing schedules were then repeated for the unused scheme. Vowel perception performance was similar across subjects and speech processing schemes. Percentage correct scores for consonant perception in noise were higher for the FB scheme than for the ZC scheme at signal-to-noise ratios ranging from 5 to 20 dB. Percentage correct scores for open set CNC words and speech tracking scores were also better for FB than for ZC.

Cochlear Implants↗
PubMed1989

Prediction of relapse or survival in patients with node-negative breast cancer by DNA flow cytometry.

More accurate prediction of the prognosis in women with node-negative breast cancer may improve physicians' ability to identify the patients most likely to benefit from systematic adjuvant therapy. With this in mind, we performed DNA flow-cytometric measurements of ploidy and the fraction of cells in the synthesis phase of the cell cycle (S-phase fraction) on 395 specimens of node-negative breast cancer from our bank of frozen tumors, using the aliquots of pulverized frozen tissue from steroid-receptor assays. The median duration of follow-up in patients still alive at the time of analysis was 59 months. Thirty-two percent of the 345 specimens that could be evaluated were diploid, and 68 percent were aneuploid. The probability of disease-free survival at five years was 88 +/- 3 percent in patients with diploid tumors and 74 +/- 3 percent in those with aneuploid tumors (P = 0.02). The S-phase fraction was not a significant additional predictor of disease-free survival in patients with aneuploid tumors. However, the probability of disease-free survival in patients with diploid tumors and low S-phase fractions was 90 +/- 3 percent at five years, as compared with 70 +/- 13 percent in those with diploid tumors and high S-phase fractions (P = 0.007). Similar differences in overall survival were noted. We conclude that DNA flow-cytometric measurements of ploidy and S-phase fraction can be performed on frozen specimens of tumors and are potentially important predictors of disease-free and overall survival in patients with node-negative breast cancer.

Breast Neoplasms↗