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Biomedical subjects

G M Clark

Publications and source records attributed to G M Clark.

At least 469 records · Page 26Linked to original sources
PubMed1983

Current distributions in cochlear stimulation.

Animal experimental studies have shown length constants of 2-4 mm for bipolar and 8-16 mm for monopolar stimulations. Studies in models using saline-solution-filled tubes have allowed us to examine the radial and longitudinal current distribution for pseudobipolar stimulation and have demonstrated that current localization is the same for bipolar and pseudobipolar stimulation over a 6-10-dB operating range. With coincident pseudobipolar multiple-channel stimulation there was suppression of the current between the stimulus maxima and enhancement at the edges leading to less stimulus interaction. Experiments performed with a pseudobipolar electrode implanted into the human cochlea showed that there was significant spread of current along the ground electrode because the electrode ground impedance was significantly greater than the cochlear tissue impedances. Because this leads to less current returned at each ground electrode, the pseudobipolar array will result in less interaction for coincident stimulation.

Animals↗
PubMed1983

Percepts from scala tympani stimulation.

The characteristics of the sensations produced by activating one electrode at a time are summarized as follows: (a) Loudness was found to increase with current level and pitch with repetition rate. (b) Pitch and sharpness increased in the apical-to-basal direction, and vowel labels could be assigned to sensations produced by individual electrodes in accordance with the tonotopical organization of the cochlea. (c) Results from triadic comparisons provided evidence that the sensations produced by repetition rate and electrode position are perceptually separable. (d) For short-duration stimuli, the discrimination performance for electrode trajectories was much better than that for repetition rate trajectories. For noncoincidental two-electrode stimulation, triadic comparisons showed that two perceptual components, one related to the more basal electrode and the other to the more apical one, could be discerned. Speech-coding considerations based on these psychophysical results are discussed.

Cochlea↗
PubMed1983

Psychophysical studies evaluating the feasibility of a speech processing strategy for a multiple-channel cochlear implant.

This paper reports further psychophysical studies on a multiple-channel cochlear implant patient evaluating the feasibility of a speech processing strategy which converts the acoustic fundamental frequency to electric repetition rate, the second-formant frequency to electrode position, and the acoustic amplitude to current level. The first four studies evaluated the use of a special pulse pattern to minimize the loudness variation with electric repetition rate. The chosen pulse pattern consisted of multiple pulses occurring in the first half of each repetitive period (MPP) in contrast to the more conventional pattern with a single pulse per period (SPP). The results showed that MPP approximately equalized the loudness variation with repetition rate. The dynamic range of current, the pitch variation with repetition rate, and the difference limens for repetition rate were found to be similar to MPP and SPP. Two other studies investigated interaction between electrode position and repetition rate (RR). The first of these showed that the patient could make use of information provided by rising or falling RR trajectories superimposed on individual electrodes or electrode trajectories as an indicator of the direction of intonation variation. The second of these studies showed that the dissimilarities amongst the hearing sensations produced by steady-state stimuli differing in electrode position and repetition rate were characterized by two perceptual components, relating to the two electric parameters, respectively.

Cochlear Implants↗
PubMed1983

Intracochlear electrical stimulation of normal and deaf cats investigated using brainstem response audiometry.

Brainstem response audiometry for intracochlear electrical stimulation of normal-hearing and deafened cats was investigated. In normal cochleas the brainstem response amplitude grew slowly near threshold as a current-amplitude dependent process, identified as electrophonic in origin. This terminated in a rapidly growing charge-dependent process at approximately 20 dB above threshold, identified as direct electrical stimulation of the auditory nerve. Small levels of white noise (25-35 dB SPL) were sufficient to mask most of the electrophonic response, leaving the direct stimulation process essentially unmodified. In cochleas damaged with d.c. currents and loud sounds, only a rapidly growing charge-dependent process was observed which grew similarly to that in normal-hearing cats but occurred at lower currents. This indicates that possibly the electrical properties of the cochlea were altered in the deafening process, suggesting the inadequacy of normal animals as deaf models for electrical stimulation. Using the technique of derived brainstem responses, it was shown that direct electrical stimulus components were localized to the vicinity of the stimulus electrode with electrophonic components distributed more widely. However, at high currents there was some evidence of the stimulus spreading into the internal auditory meatus.

Animals↗
PubMed1983

Chronic electrical stimulation of the auditory nerve in cats. Physiological and histopathological results.

The ability of spiral ganglion cells to survive long-term electrical stimulation is a precondition for the success of cochlear prostheses. In this study 10 cats were implanted bilaterally with bipolar scala tympani electrodes, and stimulated for periods of up to 2029 hours using charge balanced biphasic current pulses. The status of the auditory nerve was monitored periodically by recording electrically evoked auditory brainstem responses. At the conclusion of the stimulation program, spiral ganglion cell survival was assessed for stimulated and control cochleas; comparison of the two groups showed no statistically significant difference. The results of this study indicate that long-term intracochlear electrical stimulation, using carefully controlled biphasic pulses, does not adversely affect the spiral ganglion cell population.

Animals↗
PubMed1983

Preoperative hearing and evaluations for cochlear implant patients. A preliminary report using a Minimal Auditory Capabilities battery.

Two profoundly deaf patients were evaluated using the Minimal Auditory Capabilities (MAC) battery of speech discrimination tests. One patient was a multiple-channel cochlear implant patient (MC1) using a wearable speech-processor, the other a prospective cochlear implant patient using a hearing aid (HA). Results from the MAC battery showed that MC1 received significantly more auditory information via the speech-processor than was provided by the hearing aid to HA. These results indicated that the cochlear implant could be a suitable alternative for HA. However, the results indicated that HA gained some minimal benefit from the hearing aid and these results should be taken into consideration when deciding which ear should be implanted.

Cochlear Implants↗
PubMed1983

Prospective clinical trial of a human tumor cloning system.

A prospective clinical trial was performed to evaluate the usefulness of a human tumor cloning system for selecting single-agent chemotherapy for patients with advanced cancers. Six hundred four single-agent trials were performed in the 470 patients whose tumors were submitted for drug sensitivity testing. Only 246 of these 604 trials (41%) could be directed by the cloning system results because of inadequate tumor growth and other difficulties. In these 246 prospective trials, there was a 60% true positive and an 85% true negative rate for predicting for response or lack of response of an individual patient's tumor to the single agent. There was also a relationship between the percentage of decrease in survival of tumor colony-forming units and the probability of a clinical response of the patient's tumor to the same drug used in vivo. Despite these encouraging findings, work to improve tumor growth and additional prospective clinical trials of the system are needed before the system can be recommended for routine clinical use.

Breast Neoplasms↗
PubMed1983

Distribution of 17 beta-estradiol in the sera of normal British and Japanese women.

Normal Japanese women had significantly more of their blood 17 beta-estradiol (E2) bound to sex hormone-binding globulin (SHBG) (53%) than British women (30%) and conversely less bound to albumin. While the proportion of SHBG-bound E2 increased with SHBG capacity and while binding fell as weight increased, the differences between the races do not appear to be explicable in terms of SHBG capacity or weight. At a given SHBG capacity, the Japanese women had more E2 bound to the protein than the British women. Where weights in the 2 populations overlapped, the Japanese women still had more of their E2 bound to SHBG than did the British women. Our results suggested that the affinity of albumin for E2 is lower in Japanese women.

Adult↗
PubMed1983

The prognostic role of progesterone receptors in human breast cancer.

Estrogen-receptor protein is known to be an important prognostic factor for patients with breast cancer. The presence of estrogen receptor correlates with response to endocrine therapy in patients with metastatic disease and is associated with prolonged disease-free survival and overall survival in patients with primary disease. But the correlation between estrogen-receptor positivity and endocrine dependence is not perfect--approximately 40% of estrogen-receptor-positive tumors fail to regress with endocrine therapy. It has been hypothesized that another protein, progesterone receptor, may be a more effective marker of endocrine responsiveness since progesterone receptor is an end product of estrogen action. Promising retrospective results indicate the need for new, prospective clinical trials to define further the prognostic value of progesterone receptor for patients with advanced disease. For patients with primary breast cancer, we have found that progesterone receptor appears to be more important than estrogen receptor for predicting time to recurrence. We suggest that both estrogen receptor and progesterone receptor be routinely measured in all breast cancer tumors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Multiple estrogen receptor assays in human breast cancer.

A review of assay results from more than 6000 patients revealed 232 patients in whom multiple breast cancer specimens were analyzed for estrogen receptor (ER). All assays were performed in a single laboratory. Specimens were considered estrogen receptor positive (ER+) if the ER level was greater than 10 fmol/mg protein and estrogen receptor negative (ER-) if the ER level was less than 3. ER values between 3 and 10 fmol/mg protein were considered borderline. Simultaneous assays were performed in 58 patients with 3% major discordance (i.e., one assay ER- and one assay ER+). Major discordance for sequential biopsies was 19% (16 of 82) when the initial assay was ER+ and 13% (eight of 63) when the initial assay was ER-. (Apparent change from ER- to ER+ status was observed in five of nine patients with primary tumors less than 2 cm in diameter, suggesting that an inadequate amount of tissue may have been submitted for initial ER analysis.) There was no significant relationship between the time interval between sequential biopsies and the rate of discordance. Marked decreases in ER levels and 78% discordance were seen if rebiopsy was performed within 2 months of tamoxifen treatment. When these tamoxifen cases were excluded from the analysis, neither intervening endocrine therapy nor chemotherapy significantly altered discordance rates.

Adult↗
PubMed1983

Effects of tamoxifen on human breast cancer cell cycle kinetics: accumulation of cells in early G1 phase.

We have studied the effects of tamoxifen on the cell cycle kinetics of the endocrine-responsive MCF-7 human breast cancer cells. Tamoxifen inhibits proliferation of MCF-7 cells. The tritiated thymidine labeling index is markedly reduced by tamoxifen, indicating a reduction in the fraction of cells in S phase. Flow cytometry of mithramycin-stained cells reveals that cells accumulate in G1 phase, with a concomitant depletion of S- and G2-M-phase cells with tamoxifen. Mapping of G1-phase cells by morphology of prematurely condensed chromosomes demonstrated that tamoxifen-treated cells accumulate in early G1. These studies indicate that tamoxifen inhibits proliferation of MCF-7 human breast cancer cells by invoking a transition delay early in the G1 phase of the cell cycle.

Breast Neoplasms↗
PubMed1983

A test for serial correlation in univariate repeated-measures analysis.

A popular design in biostatistics and psychometrics is the time-factor experiment involving one grouping factor, e.g. treatment or drug, and one repeated-measures factor, e.g. time or visit. If F tests involving the repeated-measures factor are to be valid, univariate analytic procedures require special assumptions for covariance matrices across groups. The robustness of these univariate procedures is investigated when the covariance matrices do not satisfy these assumptions but have a frequently occurring form, namely the serial correlation or simplex pattern. A table is presented which shows that, for some matrices that fit the pattern, the main-effect repeated-measures estimated actual probability level is more than three times the .05 nominal level. A likelihood ratio test for the serial correlation pattern is presented, along with an example from the field of biostatistics.

Biofeedback, Psychology↗
PubMed1982

Serum concentrations of total and non-protein-bound oestradiol in patients with breast cancer and in normal controls.

In premenopausal women with breast cancer, total serum oestradiol (E2) concentrations are normal but nonprotein-bound E2 concentration are significantly raised. This is not due to low sex-hormone-binding-globulin (SHBG) binding capacities which are within the normal range and is unlikely to be due to the small but significant decrease in albumin concentrations. In post-menopausal patients, both total and non-protein-bound E2 are significantly raised: this may be explained partially by lower SHBG binding capacities. In patients and controls there is a highly significant correlation between non-protein-bound E2 and SHBG but, for a given SHBG binding capacity, the patients have more non-bound E2 than controls. It is concluded that the breast in women with breast cancer may be exposed to elevated levels of biologically active E2 although the reasons for this remain obscure.

Adult↗