Search PubMed⌕ Search

Biomedical subjects

G M Clark

Publications and source records attributed to G M Clark.

At least 235 records · Page 13Linked to original sources
PubMed1994

Speech processing for multichannel cochlear implants: variations of the Spectral Maxima Sound Processor strategy.

The Spectral Maxima Sound Processor (SMSP) incorporates a bank of 16 band-pass filters which are assigned to 16 intracochlear electrodes. In each stimulation period 6 electrodes are activated, based on the outputs of the filters with the largest amplitudes. The SMSP has previously been compared with the present MSP(MULTIPEAK) processor and found to improve speech comprehension results. The SMSP speech processing scheme has recently been implemented successfully in a new speech processor, also developed at the University of Melbourne, which utilises digital signal processing techniques. The programming flexibility of this processor has facilitated the investigation of variations of the SMSP strategy which might provide further enhancement of speech perception. Three variations have been investigated: firstly, increasing the constant pulse rate from the usual 250 Hz to 400 Hz; secondly, changing the number of electrodes selected in each stimulation period from 6 to numbers between 4 and 8; thirdly, sharpening the spectral peaks prior to selection of the active electrodes. The results of these studies showed that all three variations had minimal effect on speech perception in quiet, but that increasing the number of electrodes selected for stimulation to 8, or increasing the rate of stimulation, was advantageous for some subjects when listening in background noise.

Acoustic Stimulation↗
PubMed1994

Stimulation of residual hearing in the cat by pulsatile electrical stimulation of the cochlea.

Electrical stimulation of the cochlea may excite residual inner hair cells, either by direct electrical stimulation or through a mechanical event. Hair cell mediated responses of the auditory nerve to electrical stimulation were estimated from forward masking of the compound action potential evoked by an acoustic probe. Masking by a fixed electrical masker peaked for probes equal in frequency to the pulse repetition rate and its second harmonic, suggesting a spatially tuned profile of excitation within the cochlea. Furthermore, the tuning curves for masking of a fixed acoustic probe peaked for masker pulse rates close to the frequency of the probe. A secondary peak of masking was commonly seen for electrical stimulation at one half of the probe frequency, suggesting masking of the probe by the second harmonic of the electrical stimulus. These results suggest that pulsatile stimulation at the base of the cochlea generates a spectrally rich mechanical disturbance in which each component propagates to its place of resonance in the cochlea.

Acoustic Stimulation↗
PubMed1994

Cochlear implantation in children: labyrinthitis following pneumococcal otitis media in unimplanted and implanted cat cochleas.

Pneumococcal otitis media is frequent in young children and could lead to labyrinthitis post-implantation. To assess the risk, and methods of minimizing it by a graft to the round window around the electrode entry point, we have used a cat animal model of pneumococcal otitis media. Twenty-one kittens were used in the study. Thirty-two cochleas were implanted when the kittens were 2 months of age. Fourteen cochleas were implanted without using a graft (12 were available for study); 9 had a fascial graft, and 9 a Gelfoam graft (7 were available for study). The implanted kittens had their bullae inoculated with Streptococcus pneumoniae 2 months after implantation and were sacrificed 1 week later. There were also 9 unimplanted control ears which were inoculated when the animals were 4 months of age. Labyrinthitis occurred in 44% of unimplanted control, 50% of implanted ungrafted, and 6% of implanted grafted (fascia and Gelfoam) cochleas. There was no statistically significant difference between the unimplanted control and the implanted cochleas (p < 0.05). There was, however, a difference between the implanted-ungrafted and implanted grafted cochleas, but not between the use of fascia and Gelfoam to graft the round window entry point. As a result, the data indicates that cochlear implantation does not increase the risk of labyrinthitis following pneumococcal otitis media, but it is desirable to use fascia as a graft to the round window around the electrode entry point.

Animals↗
PubMed1994

Auditory steady-state evoked potential in newborns.

Steady-state evoked potential responses were recorded from 337 normal full-term sleeping newborns to combined amplitude and frequency modulated tones. Responses were automatically detected by statistical analysis of the response phase. Responses were most easily and consistently recorded at carrier frequencies of 500 Hz, 1500 Hz and 4000 Hz when the modulation frequency was between 60 Hz and 100 Hz. In this modulation frequency range, the response latencies were found to be between 11 ms and 15 ms, depending on carrier frequency, and the mean response thresholds for the three carrier frequencies were found to be 41.36 dB HL, 24.41 dB HL and 34.51 dB HL respectively. The results of this study suggest that steady-state evoked potentials at modulation rates in excess of 60 Hz may be useful for frequency specific, automated hearing screening in newborns.

Evoked Potentials↗
PubMed1994

Breast cancer outcome and predictors of outcome: are there age differentials?

Several questions were addressed regarding breast cancer outcome, predictors of outcome, and young age at diagnosis. Is there evidence that outcome is worse in younger women compared with other age groups? Do younger patients have a greater frequency of adverse prognostic factors? If younger age is associated with a poor outcome, is it an intrinsic independent adverse predictor, or is the outcome worse due to poor prognostic factor profiles? Several methods were used to answer these questions and applied to those reports in which age categories were carefully defined: 1) detailed review of population-based breast cancer outcome literature, 2) synthesis of published cooperative group and single institution univariate and multivariate analyses, and 3) a new analysis of the 8738-patient San Antonio database. Overall, epidemiologic studies suggested that younger women have the worst survival outcome, when matched with similarly staged older cohorts. Univariate trends analyses confirmed that younger women more often had more positive lymph nodes, larger tumors, and negative steroid hormone receptors. Significantly more cancers in women less than 35 years of age had high S-phase fractions and abnormal expression of p53. Multivariate modeling confirmed that young age was an independent adverse predictor when a few standard factors were considered in the model, but other descriptors such as tumor grade or high S-phase fraction were more important when available. These data support the conclusion that "young age" serves as a surrogate for a greater frequency of adverse prognostic factor profiles and suggest important questions for future study.

Adult↗
PubMed1994

Evaluation of a new spectral peak coding strategy for the Nucleus 22 Channel Cochlear Implant System.

Sixty-three postlinguistically deaf adults from four English-speaking countries participated in a 17-week field study of performance with a new speech coding strategy, Spectral Peak (SPEAK), and the most widely used strategy, Multipeak (MPEAK), both of which are implemented on wearable speech processors of the Nucleus 22 Channel Cochlear Implant System; MPEAK is a feature-extraction strategy, whereas SPEAK is a filterbank strategy. Subjects' performance was evaluated with an experimental design in which use of each strategy was reversed and replicated (ABAB). Average scores for speech tests presented sound-only at 70 dB SPL were higher with the SPEAK strategy than with the MPEAK strategy. For tests in quiet, mean scores for medial vowels were 74.8 percent versus 70.1 percent; for medial consonants, 68.6 percent versus 56.6 percent; for monosyllabic words, 33.8 percent versus 24.6 percent; and for sentences, 77.5 percent versus 67.4 percent. For tests in noise, mean scores for Four-Choice Spondees at +10 and +5 dB signal-to-noise ratio (S/N) were 88.5 percent versus 73.6 percent and 80.1 percent versus 62.3 percent, respectively; and for sentences at +15 dB, +10, and +5 dB S/N, 66.5 percent versus 43.4 percent, 61.5 percent versus 37.1 percent, and 60.4 percent versus 31.7 percent, respectively. Subjects showed marked improvement in recognition of sentences in noise with the new SPEAK filterbank strategy. These results agree closely with subjects' responses to a questionnaire on which approximately 80 percent reported they heard best with the SPEAK strategy for everyday listening situations.

Adult↗
PubMed1993

A randomized phase I trial of chronic oral etoposide with or without granulocyte-macrophage colony-stimulating factor in patients with advanced malignancies.

Data from an in vitro human tumor-cloning assay suggested synergistic cytotoxicity when etoposide (VP16) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were combined. To explore this potential, we undertook a prospectively randomized three-arm trial in a phase I setting with various schedules of VP16 and GM-CSF. Thirty-one patients were enrolled in the three-arm trial. Arm A consisted of oral VP16 daily for up to 21 days with cycles repeated every 35 days. Arm B included oral VP16 daily for up to 21 days plus concomitant GM-CSF at 5 micrograms/kg/day s.c. days 1-10. Arm C included oral VP16 daily for up to 21 days plus pretreatment with GM-CSF at the same dose for 5 days (days -6 to -2). VP16 was begun at 25 mg/m2/day on level 1 and increased to 50 mg/m2/day on level 2. Twenty-seven patients were evaluable for toxicity, nine on each arm (six patients on each arm on level 1, three patients on each arm on level 2). Neutropenia on arm B (concomitant VP16 and GM-CSF) was earlier and more profound than on arm A or C. The median absolute neutrophil count and day of nadir for arms A, B, and C were 3295, 988, and 1600/mm3 and days 23, 15, and 26, respectively. Thrombocytopenia was generally uncommon except on arm C level 2, where the median platelet count was 26,000/mm3. One partial response (arm B) in a patient with non-small cell lung cancer was seen. Dose intensity favored arm A. Neither concomitant therapy with VP16 and GM-CSF (arm B) nor pretreatment with GM-CSF (arm C) improved dose intensity over VP16 alone (arm A), and arms B and C were complicated by increased neutropenia and thrombocytopenia.

Adolescent↗
PubMed1993

Insulin-like growth factor-I receptors are overexpressed and predict a low risk in human breast cancer.

IGF-I receptor (IGFR) content and its prognostic significance were evaluated in human breast cancer specimens using a sensitive and specific radioimmunoassay (V. Pezzino et al., Metabolism, 40: 861, 1991). The prognostic significance of IGFR expression was investigated by two different approaches: (a) detectable IGFR content was measured in 82% of specimens in a consecutive series of 184 human breast cancers and in 32% of 19 normal breast tissues. The average IGFR content in breast cancer was nearly 10-fold higher than the value observed in normal breast tissue (7.6 +/- 0.8 versus 0.8 +/- 0.1 ng/0.1 mg protein, mean +/- SEM; P < 0.001). IGFR content was positively correlated with estrogen (ER) and insulin receptor content (r = 0.269 and 0.515, respectively, Pearson correlation) but not with progesterone receptors (PR). No significant correlation was observed between IGFR content and a variety of tumor parameters (tumor size, lymph node involvement, grade) and host characteristics (age, body mass index, menopausal status); (b) IGFR content was measured in a noncontinuous series of 265 primary breast cancer specimens subdivided into 136 high-risk and 129 low-risk specimens on the basis of being either negative (ER-/PR-/aneuploid/high S-phase) or positive (ER+/PR+/diploid/low S-phase) for four well-established prognostic factors. IGFR levels were significantly higher in the low-risk group (6.4 +/- 0.4 ng/0.1 mg protein, mean +/- SEM) than in the high-risk group (3.6 +/- 0.5; P < 0.0001, Wilcoxon sum rank test). In summary, our data indicate that there is an elevated IGFR content in most human breast cancers compared with normal breast tissue and that an elevated IGFR content is a favorable prognostic indicator.

Adult↗
PubMed1993

Heat shock protein hsp70 in patients with axillary lymph node-negative breast cancer: prognostic implications.

BACKGROUND: Cell synthesis of heat shock (stress-response) proteins is increased by a variety of environmental and pathophysiological stressful conditions. The 70-kd heat shock protein (hsp70) is thought to be involved in protein-protein interactions including those of the protein products of the human c-myc oncogene and the p53 (also known as TP53) tumor suppressor gene. PURPOSE: The purpose of this study was to investigate whether elevated hsp70 expression may be an indicator of biological stress experienced by a breast cancer and may, therefore, predict disease outcome. METHODS: Levels of hsp70 were determined by Western blot analysis in primary breast tumors from patients with negative axillary lymph nodes. We performed exploratory data analyses on a set of 162 primary breast cancers and constructed prognostic indexes of hsp70 expression levels. The optimal cutpoint for hsp70 expression was considered to be the value yielding the greatest separation for disease-free survival for the resulting two groups of patients. That cutpoint was then validated in a set of 345 tumors by univariate and multivariate analyses. Data were analyzed for overall survival, disease-free survival, tumor size, and patient age, as well as estrogen receptor and progesterone receptor status, ploidy (DNA content), and percentage of cells in S phase as determined by flow cytometry. RESULTS: Expression of hsp70 emerged as a useful prognostic factor, both in univariate and in multivariate analyses. Patients whose tumors had high expression of hsp70 had significantly shorter disease-free survival (P = .006). The other statistically significant factors were S-phase fraction (P = .008) and tumor size (P = .01). For patients who received adjuvant therapy, hsp70 was the only independent predictor of disease recurrence (P = .05). For those with tumors 1-3 cm in diameter, hsp70 (P = .008) and S-phase fraction (P = .02) were statistically significant predictors of recurrence. CONCLUSIONS: Measurement of hsp70 expression in primary tumors from patients with node-negative breast cancer may be useful in identifying patients at high risk for disease recurrence and thus may affect decisions regarding treatment after surgery. IMPLICATIONS: Future studies should be performed to determine if detection of hsp70 by immunohistochemistry can be used to predict clinical outcome and to better understand the relationships between hsp70 and the effects of various treatment modalities.

Analysis of Variance↗
PubMed1993

Applicability of flow cytometry in breast cancer.

The cumulative evidence indicates that flow cytometry can provide important information about the behavior of breast tumors. A particularly appealing aspect of this technology is the ability to determine flow cytometric parameters on fresh surgical samples, frozen biopsy specimens, and archival paraffin-embedded blocks. However, several issues regarding the standardization of tissue preparation and the cell cycle analyses must be addressed before flow cytometry can be routinely applied on a wide scale. Quality control standards are currently being discussed that will help to reduce interlaboratory variability, particularly with respect to absolute values of S-phase fraction.

Breast Neoplasms↗
PubMed1993

How to integrate steroid hormone receptor, flow cytometric, and other prognostic information in regard to primary breast cancer.

A large group of patients with node-positive breast cancer was divided into a training set (n = 851) and a validation set (n = 432) to demonstrate techniques for integrating steroid hormone receptor status, DNA flow cytometric findings, and other prognostic factors to predict patient survival. Multivariate analyses showed that estrogen receptor status, the number of involved axillary lymph nodes, patient age, S-phase fraction, progesterone receptor status, and tumor size were significant predictors of survival in patients with node-positive breast cancer. Techniques for optimizing and validating a cut point for a new prognostic factor and for examining alternative representations of prognostic factors were demonstrated. Prognostic indexes were created that could be used to identify patients with very good or very poor prognoses.

Aneuploidy↗
PubMed1993

Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer.

BACKGROUND: The p53 (also known as TP53) tumor suppressor gene encodes for a nuclear phosphoprotein thought to regulate proliferation of normal cells. Most p53 mutations result in a nonfunctional protein that accumulates in tumor cell nuclei. These common mutations appear to be involved in the development and/or progression of several neoplastic diseases including human breast cancer. PURPOSE: Our purpose was to investigate the relationships between levels of mutant p53 protein expression, tumor cell proliferation rate, and clinical outcome in patients with node-negative breast cancer. METHODS: Expression of mutant p53 protein was evaluated by frozen-section immunohistochemistry (IHC) and light microscopy in 700 breast cancers from axillary lymph node-negative patients with long-term follow-up (median, 54 months). The immunostaining signal was expressed as the sum of scores representing the proportion and staining intensity of negative and positive tumor cell nuclei (ranges, 0 and 2-8, respectively). Statistical comparisons were made between levels of p53 protein expression and disease-free survival, overall survival, and tumor proliferation rate expressed as the percentage of cells in the S phase (%S phase) as determined by flow cytometry. RESULTS: Of the 700 tumors, 362 (52%) showed positive nuclear immunostaining (IHC score > 0). Proliferation rates were significantly higher (P = .0001) in positive tumors (median %S phase, 7.1%) than in negative tumors (4.1%). In a univariate cutpoint analysis, negative tumors (n = 388) versus low-positive tumors (IHC score = 2-6; n = 263) versus high-positive tumors (IHC score > 6; n = 99) showed progressively reduced disease-free survival (80% versus 72% versus 58% at 5 years, respectively; P < or = .05 for all pairwise comparisons). Analogous results for overall survival were 88% versus 84% versus 74%; only the result for negative versus high positive tumors was significant (P = .003). In a multivariate analysis, expression of p53 protein and high %S phase were independently associated with reduced disease-free survival (P = .008 and .01, respectively). CONCLUSIONS: Expression of mutant p53 protein was associated with high tumor proliferation rate, early disease recurrence, and early death in node-negative breast cancer. Despite the strong direct correlation between accumulation of p53 protein and tumor proliferation rate, both factors were independently associated with poor prognosis, suggesting that p53 may have other biological functions in addition to cell-cycle regulation. IMPLICATIONS: This test, when combined with other prognostic factors, may enhance our ability to identify node-negative breast cancer patients at high risk for early disease recurrence and/or death, for whom the use of adjuvant chemotherapy is unequivocally justified.

Adult↗
PubMed1993

Combined electrical and acoustical stimulation using a bimodal prosthesis.

A new device incorporating a cochlear implant speech processor and a speech-processing hearing aid for the unimplanted ear has been designed and tested with four severely hearing-impaired patients. The aim of the device is to provide a more acceptable and effective combination of electrical and acoustic signals to the two ears. When used monaurally, and binaurally in conjunction with the cochlear implant, the speech-processing hearing aid mean scores for open-set sentences, words, and consonants were as good as or better than the mean scores for the patients' own conventional hearing aids. Some patients improved much more than did others. Although not conclusive, these results are encouraging, especially as they were achieved with a laboratory prototype that did not allow the patients to become accustomed to the processor in everyday situations.

Adult↗
PubMed1993

Pediatric cochlear implantation. Radiologic observations of skull growth.

We investigated the effects of long-term implantation of auditory prostheses on skull growth in young animals. Four monkeys were implanted with dummy cochlear implants at 6 months of age. To simulate implantation in children, the bed for the receiver-stimulator or interconnecting plug was drilled across a calvarial suture down to the underlying dura. Plain skull roentgenograms were periodically taken to monitor head growth for up to 3 years after implantation. These longitudinal measurements revealed no significant asymmetric skull growth. Postmortem measurements using computed tomographic scans confirmed these results and showed no significant difference in the intracranial volumes between the implanted and control sides of each animal or between experimental and nonimplanted control monkeys. These results suggest that long-term cochlear implantation in very young children will not cause any significant deformity of the skull.

Animals↗
PubMed1993

Neural Network Analysis of DNA flow cytometry histograms.

A pattern recognition system based on Neural Network Analysis, a form of artificial intelligence, was used to search DNA flow cytometry histograms for features that correlated with breast cancer patients' risk of relapse. DNA flow cytometry histograms and clinical follow-up information from 796 breast cancer patients were used to train a Neural Network to predict the clinical outcome of patients in a separate independent set of 794 patients. Median follow-up in this patient data base was short, 23 months. Neural Network Analysis resulted in a model that evaluated DNA flow cytometry histograms differently than conventional analysis, which categorizes the histograms by ploidy and S-phase fraction. Neural Network Analysis appeared to identify low risk and high risk subsets of patients as accurately as conventional analysis. Neural Network Analysis placed heavy emphasis on the region to the right of the diploid G2/M peak, where a subpopulation of nuclei with high DNA content is seen even in many histograms scored as diploid by conventional techniques. The number of nuclei in this region was found to be a powerful predictor of patient outcome, and multivariate analysis showed that the number of nuclei in this region and the S-phase fraction both were independently predictive of relapse. This pilot study suggests that conventional analysis (based on a mechanistic interpretation of regions in flow cytometry histograms) might be used in conjunction with and improved by pattern recognition systems or insights derived from them.

Breast Neoplasms↗
PubMed1993

Surrogate endpoints in chemoprevention of breast cancer: guidelines for evaluation of new biomarkers.

Markers of early events in the development of breast cancer are potential candidates for surrogate endpoints in chemoprevention trials. There are many such markers and the challenge is to identify truly relevant markers. If successful, surrogate endpoints offer several potential benefits in the conduct of prevention trials, including: shorter latency and hence shorter trials; reductions in size and cost of trials; and the opportunity to study prevention measures where use of primary outcomes would be excessively invasive or unethical. Although there are currently no validated surrogate endpoints for breast cancer, criteria for the discovery and validation of surrogates have been proposed. Putative surrogate endpoints should be biologically plausible, represent an early event in the causal pathway, be measurable by a standardized and reliable assay, and exhibit a dose-response. Perhaps most importantly, surrogates should statistically capture the effect of the intervention on outcome. The identification and establishment of a biomarker as a valid surrogate for cancer is a stepwise process that involves both smaller "transitional" studies and larger second-generation chemoprevention trials in which both primary outcome and putative surrogates are measured. Transitional studies are used to move new markers from the laboratory into use in human populations, and are designed to address specific questions of assay validity, treatment/marker associations, marker/disease associations, and inter- and intra-individual variability. Promising markers should be added to current and planned, large, traditionally designed chemoprevention trials in order to definitively address the issues of optimal representation, and to test the adequacy with which the marker(s) captures the effect of treatment on outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗