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Biomedical subjects

G M Clark

Publications and source records attributed to G M Clark.

At least 379 records · Page 21Linked to original sources

Preliminary evaluation of a multichannel electrotactile speech processor.

Speech discrimination testing, using both open- and closed-set materials, was carried out with four severely to profoundly hearing impaired adults and seven normally hearing subjects to assess performance of a wearable eight-channel electrotactile aid (Tickle Talker). Significant increases in speechtracking rates were noted for all subjects when using the electrotactile aid. After 70 h of training, mean tracking rate in the tactile plus lipreading condition was 55 words per minute (wpm), as compared with 36 wpm for lipreading alone, for the normally hearing group. For the hearing impaired group, the mean tracking rate in the aided condition was 37 wpm, as compared with 24 wpm for lipreading alone, following 35 h of training. Performance scores on Central Institute for the Deaf (CID) everyday sentences, Consonant Nucleus Consonant (CNC) words, and closed-set vowel and consonant identification were significantly improved when using the electrotactile aid. Performance scores, using the aid without lipreading, were well above chance on consonant and vowel identification and on elements of the Minimal Auditory Capabilities Battery. Two hearing impaired subjects have used the device satisfactorily in the home environment.

Adult↗

Synthetic vowel studies on cochlear implant patients.

Speech perception studies were conducted on three cochlear implant patients to investigate the relative merits of six speech processing schemes for presenting speech information to these patients. Electrical stimuli, described in this article as synthetic vowels, were constructed using tabulated data of formant frequencies of natural vowels. The six schemes differed in the number of formant frequencies encoded on the electrical signal dimension of electrode position, and/or in the range of electrode position used for encoding each formant frequency. Eleven synthetic vowels (i, I, E, ae, a, c, U, u, v, E, D) were used and were presented in a single-interval procedure for absolute identification. Single-formant vowels were used in two of the six schemes, two-formant vowels in three schemes, and three-formant vowels in the remaining scheme. The confusion matrices were subjected to conditional information transmission analysis on the basis of previous psychophysiological findings. Comparisons among the schemes in terms of the analyzed results showed that training, experience, and adaptability to new speech processing schemes were major factors influencing the identification of synthetic vowels. For vowels containing more than one formant, the information about each formant affected the perception of the other formants. In addition, there appeared to be differences between the perceptual processes for vowels containing more than one formant and the processes for single-formant vowels. Taking into consideration the effects of training, experience, and adaptability, the three-formant speech processing scheme appeared, on the basis of perceptual performance comparisons among the six schemes, to be the logical choice for implementation in speech processors for cochlear implant patients.

Aged↗

Perceptual studies on cochlear implant patients with early onset of profound hearing impairment prior to normal development of auditory, speech, and language skills.

Psychophysical studies were conducted on three prelingual and two postlingual cochlear implant patients. Auditory sensations were produced by electrical stimulation of the residual nerve fibers of the auditory nerve by means of a multiple-electrode cochlear implant. The psychophysical performance of the prelinguals was, in general, poorer than that of the postlinguals; prelingual performance was poorer for repetition rate and electrode position identification, gap detection, and durational and numerosity judgments. Improved performance with time, however, was consistently observed for the prelinguals in the above-mentioned psychophysical tasks. There were significant individual differences in the amount of improvement among the three prelinguals. Speech perception studies were also conducted on the three prelingual patients. The speech perception performance of the three prelingual patients was much poorer than that of postlingual patients in general, and was consistent with their poorer psychophysical performance described above.

Adolescent↗

Effect of tamoxifen on oestrogen binding, lipid and lipoprotein concentrations and blood clotting parameters in premenopausal women with breast pain.

As part of a controlled trial of the use of tamoxifen for the treatment of mastalgia, some of the metabolic and haematological effects of this agent were measured. A panel of haemostatic variables including prothrombin time, kaolin cephalin clotting time, fibrinogen, euglobulin lysis time, factor VII, factor VIII, protein C and anti-thrombin III were determined. In addition, levels of sex hormone-binding globulin and both total and free oestradiol were estimated. No alteration in clotting function was found during the administration of tamoxifen, although hepatic function did alter during this period with an increase in concentration of sex hormone-binding globulin. There was a significant increase in total oestradiol and free oestradiol although the percentage of biologically available free oestradiol fell slightly during the course of tamoxifen treatment. There was a slight reduction in low-density lipoprotein cholesterol with an increase in HDL2, a subclass of high-density lipoprotein (HDL) cholesterol, consistent with an oestrogen-agonist effect. These data suggest that tamoxifen administration does not adversely influence haemostatic mechanisms or lipoprotein metabolism in the short term.

Adult↗

Initial experience with children using the Nucleus 22 Channel cochlear implant.

The Nucleus 22 Channel cochlear prosthesis developed by the University of Melbourne and Cochlear Pty Ltd is now being used in over 90 clinics worldwide, in fourteen countries and fifteen languages. A total of thirty adolescents and thirty-nine children have now been implanted in Australia, America and more recently Germany. There have been no significant postoperative complications, and the device has been successfully programmed in children as young as two years nine months. Comprehensive evaluation and training programs are being undertaken with each implanted child to assess long term development of speech perception and communication skills. The average postoperative stimulation time for most of the children implanted is around 3 months, so as yet, little data has been recorded on these patients. However, the two original children implanted in Melbourne have now been using their speech processors in excess of 18 months. The focus of this paper will be on the performance of these two children.

Child↗

Steroid receptors and other prognostic factors in primary breast cancer.

A review and update of published studies on prognostic factors support the following conclusions: The number of axillary lymph nodes involved with tumor remains the most important prognostic factor for women with primary breast cancer. In stage I disease, the lack of estrogen receptor (ER) seems to be the most important factor for predicting earlier recurrence and poorer survival. In stage II breast cancer, progesterone receptor (PgR) content appears to be better than ER content in predicting disease-free and overall survival. Measurement of proliferative activity (S-phase DNA) by thymidine labeling or flow cytometry (FCM) and of aneuploidy by FCM also provides prognostic information. Patients with aneuploid tumors, or with high S-phase diploid tumors, are at increased risk for relapse. Amplification of oncogenes, particularly HER-2/neu, may provide additional prognostic information in combination with other established prognostic factors.

Breast Neoplasms↗

The biologic safety of the Cochlear Corporation multiple-electrode intracochlear implant.

Studies have been undertaken to confirm the biologic safety of the Cochlear Corporation multi-electrode intracochlear implant. The materials used are biocompatible. The electrode array is flexible: it can be inserted with minimal or no trauma, providing the insertion is stopped when resistance is first felt. An atraumatic insertion is facilitated if a good view is obtained along the scala tympani of the basal turn of the cochlea by drilling through the crista fenestrae. The passage of the electrode around the cochlea can be facilitated if the electrode is rotated during insertion (clockwise for the left and anticlockwise for the right cochlea). The electrode can be explanted and another one reinserted with minimal or no trauma. A seal established around the electrode after an implantation period of 2 weeks can prevent infection extending from the middle to the inner ear. The electrical stimulus parameters produced by the Nucleus receiver-stimulator cause no loss of spiral ganglion cells or corrosion of the platinum band electrodes. Long-term stimulation has been carried out for up to 8 years in patients without affecting their clinical performance.

Animals↗

A radiometric method for evaluation of chemotherapy sensitivity: results of screening a panel of human breast cancer cell lines.

We have used a radiometric method to screen for chemotherapy sensitivity among a panel of human breast cancer cell lines. This method utilizes the inhibition of conversion of [14C]glucose to 14CO2 as an index of cytotoxicity. Nine different breast cancer cell lines were exposed for 1 h to 4 different concentrations of several antineoplastic agents with and without documented clinical activity against breast cancer. Cytotoxic effects were analyzed as a function of the ratio of the concentration required to inhibit cell growth to 50% of control to 1/10 of the known peak plasma concentration in humans for each particular drug. The drug-induced inhibition of 14C production by breast cancer tumor cells correlated strongly with the drug-induced antiproliferative effect (P less than 0.002) and with the inhibition of colony formation in a soft agar cloning assay (P less than 0.05). The HS578T cell line and one of the MCF7 cell lines exhibited a chemosensitivity pattern consistent with the clinical responsiveness of human breast cancer to the agents tested. Most of the other cell lines exhibited resistance to clinically active agents, especially the cell lines obtained from patients exposed to prior chemotherapy. These results suggest that this radiometric method measures a drug-induced metabolic effect that correlates with the antiproliferative activity of antineoplastic agents on breast cancer cells. The HS578T and the MCF7-KO cell lines, tested in this system, could be a useful screen for new anticancer compounds with activity against human breast cancer.

Antineoplastic Agents↗

Evaluation of a modeling system for S-phase estimation in breast cancer by flow cytometry.

Using software programs provided by Coulter Electronics, we have developed an analysis system that would address problems encountered in DNA flow cytometric analysis of heterogeneous solid tumor populations, especially where the G2-M phase of the diploid population contaminates the S-phase of the aneuploid population, causing an overestimation of cells in S phase. We used the PARA 1 and PARA 2 programs in concert and developed three analysis models: (a) for euploid tumors; (b) for hyperdiploid tumors with overlapping populations; and (c) for near-diploid aneuploid tumors. Our purpose in this paper is to determine the limits and reproducibility of this analysis system with an emphasis on tumors with overlapping populations. Aliquots of frozen, pulverized breast tumor tissue (50 to 100 mg), routinely used in the steroid receptor assay, were used for routine flow cytometric measurement of the DNA index and S-phase fraction. To determine the accuracy of the analysis when overlapping populations were present, we mixed an aneuploid breast cancer cell line with human blood lymphocytes in varying ratios. A 10% mixture of aneuploid cells, the lowest mixture tested, still allowed analysis results within 95% confidence limits. Reproducibility of the system was assessed on frozen breast tumor tissue by intra- and interassay variation studies measuring cell cycle parameters and coefficient of variation of the G0-G1 peak width. Within any sample the amount of variation (+/- 2 SD) for the G0-G1 value was +/- 4.40 for intraassay and +/- 4.60 for interassay, and the amount of variation for S phase was +/- 3.0 and +/- 3.2 for intraassay and interassay, respectively. There was no difference in the variation of estimates for G2-M (+/- 2.6 for both intra- and interassay). In this study, the coefficient of variation of the G0-G1 peak greater than 5% was defined as unacceptable for accurate analysis, with the conclusion that S-phase fractions in aneuploid tumors can be routinely analyzed in human breast tumor biopsies despite tumor cell heterogeneity.

Aneuploidy↗

Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.

The HER-2/neu oncogene is a member of the erbB-like oncogene family, and is related to, but distinct from, the epidermal growth factor receptor. This gene has been shown to be amplified in human breast cancer cell lines. In the current study, alterations of the gene in 189 primary human breast cancers were investigated. HER-2/neu was found to be amplified from 2- to greater than 20-fold in 30% of the tumors. Correlation of gene amplification with several disease parameters was evaluated. Amplification of the HER-2/neu gene was a significant predictor of both overall survival and time to relapse in patients with breast cancer. It retained its significance even when adjustments were made for other known prognostic factors. Moreover, HER-2/neu amplification had greater prognostic value than most currently used prognostic factors, including hormonal-receptor status, in lymph node-positive disease. These data indicate that this gene may play a role in the biologic behavior and/or pathogenesis of human breast cancer.

Axilla↗

Cancer and resuscitation. Does the diagnosis affect the decision?

We asked if physicians are less likely to resuscitate patients with cancer because of the diagnostic label alone. We composed a questionnaire of nine patient vignettes with similar expected mortality rates, identical quality of life, and witnessed cardiopulmonary arrest. Internists and neurologists in a university training program were asked to decide, for each "patient," whether to administer cardiopulmonary resuscitation (CPR) before and after being informed of similar mortality rates. Decisions for CPR were less frequent for cancer vignettes than for vignettes of other chronic medical illnesses before and after mortality information was given. Analysis indicated that decisions varied among physicians according to their subspecialties. Overall, women favored resuscitation less often than did men. The diagnosis of cancer appears to have a negative impact on physicians' CPR decisions over and above that due to inaccurate prognostic assumptions about cancer. A physician's subspecialty and gender may also influence resuscitation decisions for patients in general.

Aged↗

A multiple-electrode intracochlear implant for children.

A multiple-electrode intracochlear implant that provides 21 stimulus channels has been designed for use in young children. It is smaller than the adult version and has magnets to facilitate the attachment of the headset. It has been implanted in two children aged 5 and 10 years. The two children both lost hearing in their third year, when they were still learning language. Following implantation, it was possible to determine threshold and comfortable listening levels for each electrode pair. This was facilitated in the younger child by prior training in scaling visual and electrotactile stimuli. Both children are regular users of the implant, and a training and assessment program has been commenced.

Child↗

Centrifugal ultrafiltration-dialysis for non-protein-bound oestradiol in blood: importance of the support.

The percentage of non-protein-bound oestradiol in serum or other fluid measured by centrifugal ultrafiltration-dialysis was critically dependent on the supporting medium used to collect the ultrafiltrate. When either Whatman No. 1 filter paper discs, Whatman GF/D glass fibre discs or Celite were used, the ratios of 3H-steroid to [14C]glucose on the support were found to change with centrifugation time. This occurred when serum or protein-free filtrates were analysed and was eliminated when silanised Celite was employed as the support. It was also observed that when serum was analysed, the [3H]/[14C] ratio inside the cell increased linearly with centrifugation time and this was ascribed to the small changes in volume which occurred inside the cell as ultrafiltrate accumulated on the support. It was concluded that the correct time to sample the ratio of [3H]/[14C] inside was before centrifugation.

Carbon Radioisotopes↗