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Biomedical subjects

G M Clark

Publications and source records attributed to G M Clark.

At least 433 records · Page 24Linked to original sources
PubMed1985

A comparison of three speech coding strategies using an acoustic model of a cochlear implant.

Three alternative speech coding strategies suitable for use with cochlear implants were compared in a study of three normally hearing subjects using an acoustic model of a multiple-channel cochlear implant. The first strategy (F2) presented the amplitude envelope of the speech and the second formant frequency. The second strategy (F0 F2) included the voice fundamental frequency, and the third strategy (F0 F1 F2) presented the first formant frequency as well. Discourse level testing with the speech tracking method showed a clear superiority of the F0 F1 F2 strategy when the auditory information was used to supplement lipreading. Tracking rates averaged over three subjects for nine 10-min sessions were 40 wpm for F2, 52 wpm for F0 F2, and 66 wpm for F0 F1 F2. Vowel and consonant confusion studies and a test of prosodic information were carried out with auditory information only. The vowel test showed a significant difference between the strategies, but no differences were found for the other tests. It was concluded that the amplitude and duration cues common to all three strategies accounted for the levels of consonant and prosodic information received by the subjects, while the different tracking rates were a consequence of the better vowel recognition and the more natural quality of the F0 F1 F2 strategy.

Adult↗
PubMed1985

Clinical results with a hearing aid and a single-channel vibrotactile device for profoundly deaf adults.

The speech perception of a group of 19 adults with post-lingual profound to total hearing loss was tested with nine closed-set speech tests without lipreading, two open-set tests without lipreading and two open-set speech tests with lipreading. The subjects were all prospective cochlear implant patients participating in a clinical trial of the implant and the results reported here were obtained as part of the pre-operative assessment. They were divided into groups on the basis of their prior experience with the aid(s), their speech detection thresholds with the two aids and their personal preferences. Seven of the subjects used a hand-held single-channel vibrotactile device and the other 12 used a powerful conventional hearing aid. Subjects from each group scored significantly better than chance on the closed set tests without lipreading. Training or regular hearing aid use was correlated with good performance on the closed-set tests. No subject showed a significant improvement of the lipreading score when the aid was used as a supplement. The use of sophisticated wearable tactile devices and extensive training may allow a better result, but in this clinical program, neither a hearing aid nor a single-channel vibrotactile device greatly benefited the postlingually profoundly deaf adults.

Adult↗
PubMed1985

Breast cancer prognosis in a mixed Caucasian-Hispanic population.

Prognostic factors were compared between 1,249 Caucasian and 360 Hispanic women with breast cancer. A significantly greater proportion of Hispanic women were less than 50 years of age at diagnosis compared to Caucasian women (P less than .0001). Significantly more Hispanic women presented with tumors larger than 3 cm in diameter and with positive axillary lymph nodes than did Caucasian women (P = .004 and P = .0001, respectively). Significantly more Hispanic women were estrogen receptor (ER) negative (P = .005). However, when examined by age groups, the relationships between ethnicity and extent of disease and ER status were observed only among women over 50 years of age. Multivariate analyses demonstrated that there was no difference in survival between Caucasian and Hispanic women once adjustments were made for the number of positive lymph nodes and ER status. Although complete data were not available, it appeared that the incidence of breast cancer is lower in this population of Hispanic women than in Caucasian women.

Age Factors↗
PubMed1985

Effect of estrogens and antiestrogens on growth of human breast cancer cells in athymic nude mice.

Endocrine therapy with estrogen deprivation or with antiestrogens results in tumor regression in a subset of patients with advanced breast cancer. To better understand the mechanisms by which estrogens and antiestrogens modulate breast cancer growth in vivo, we have studied the effects of endocrine manipulation on the development and growth of tumors derived from cultured human breast cancer cells in the athymic nude mouse. MCF-7 breast cancer cells were inoculated into 6-week-old female BALB/c athymic nude mice. Tumor growth did not occur in ovariectomized mice. Cells remained viable, however, since estrogen supplementation more than 30 days later resulted in tumor formation. Minimal tumor growth was observed in intact female nude mice which have low circulating estrogen levels. Tumor development and growth in ovariectomized or intact mice supplemented with 17 beta-estradiol in the form of a s.c. pellet were dose dependent; growth rates increased with estrogen doses ranging from 0.01 to 0.5 mg. Antiestrogen treatment with either tamoxifen or LY156758 caused transient stimulation of tumor growth, followed by a prolonged stationary phase. Growth resumed with estrogen supplementation. Treatment of mice bearing established MCF-7 tumors with estrogen withdrawal (removal of estrogen pellet) resulted in cessation of tumor growth, but not in tumor regression. Growth inhibition was also observed with antiestrogens and was dose dependent. However, tumor regression did not occur, even in mice treated with high doses of tamoxifen (serum concentration of 1.0 microM) for as long as 60 days. Tumor growth was restored in these mice with estrogen replenishment. Tumor cells also remained viable histologically despite prolonged (1 month) estrogen deprivation or antiestrogen therapy, although the mitotic index was markedly reduced. Similar observations were made with mice inoculated with the hormone-responsive ZR75-1 human breast cancer cells, but not with hormone-independent MDA-231 cells which were not influenced by estrogen or antiestrogen treatment. In summary, development and growth of MCF-7 and ZR75-1 tumors in nude mice are estrogen dependent. Endocrine therapy by estrogen deprivation or antiestrogen treatment inhibits tumor cell proliferation in nude mice, but does not cause tumor regression or loss of cell viability.

Animals↗
PubMed1985

Role of progesterone receptors in breast cancer.

It has been demonstrated that progesterone receptor (PR) is at least as valuable as estrogen receptor (ER) for predicting the outcome in breast cancer patients. Retrospective analysis indicates that presence of PR may be the second most critical factor, after the number of positive nodes, in predicting for disease-free survival, with a correlation between length of survival and number of tumor PR. The presence of PR has been shown to be of value for predicting response in both early and advanced breast cancer patients. In studies of assay consistency, major discordance rates were minimal in simultaneous assays but extremely high in sequential assays of tumors that were PR positive in initial assay. The responsible factor was interim endocrine therapy, and it was subsequently determined that prognosis was worse for those patients whose tumors lost PR between assays.

Breast Neoplasms↗
PubMed1985

Phase I evaluation and pharmacokinetics of tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, NSC 286193).

Tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, TCAR, Riboxamide, NSC 286193) is a novel C-nucleoside with antitumor activity against several murine tumor models, including Lewis lung carcinoma. The mechanism whereby this compound exerts its antineoplastic effects is most likely related to a state of guanine nucleotide depletion whereby the anabolite, thiazole-4-carboxamide adenine dinucleotide, potently inhibits inosine-5'-monophosphate dehydrogenase. This Phase I study was designed to determine the maximally tolerated dose of Tiazofurin administered on a 5-day, every-28-day schedule. Tiazofurin levels were measured using a high-pressure liquid chromatography assay, and pharmacokinetic studies were performed in patients treated at each dose level. Nineteen patients received a total of 24 courses of the drug in doses ranging from 550 to 2200 mg/sq m. The dose-limiting toxicities were pleuropericarditis and a general illness best described as a "viral-like" syndrome (manifested by severe malaise, headaches, myalgias, fever, nausea, vomiting, and diarrhea). Other toxicity included myelosuppression, hyperuricemia, elevated serum creatine phosphokinase and serum glutamic oxaloacetic transaminase, conjunctivitis, mucositis, and desquamation of the palms of the hands. Plasma clearance of Tiazofurin followed a biexponential pattern with a harmonic mean terminal half-life of 7.6 h. The mean volume of distribution at steady state was 30 liters/sq m, and the mean plasma clearance was 3 liters/h/sq m. The total cumulative urinary excretion ranged from 15 to 49%. The maximally tolerated dose of Tiazofurin on a 5-day schedule was 1650 mg/sq m. The recommended dose for Phase II evaluations is 1100 mg/sq m for 5 days. However, exploration of other schedules which might allow administration of more Tiazofurin combined with biochemical studies including thiazole-4-carboxamide adenine dinucleotide measurements would be desirable.

Adult↗
PubMed1985

In vitro comparison of vinzolidine and vinblastine: a model for methods of evaluation of analogues in a human tumor cloning system.

Four statistical techniques are described for comparing the in vitro cytotoxic activity of an analogue and its parent compound in the human tumor cloning system. These techniques include: the Spearman rank correlation coefficient; a sequential pairwise analysis; the kappa statistic for measuring agreement; and the McNemar test of symmetry. These statistical procedures were applied to results from 54 human tumor specimens that were simultaneously tested against multiple concentrations of the Vinca alkaloid vinblastine and its semisynthetic analogue, vinzolidine. Based on the percentage of survival of tumor colony-forming units in the human tumor cloning system, vinzolidine was shown to have a 26% in vitro response rate with a spectrum of activity across major tumor types. However, all four statistical procedures indicated that the activity of vinzolidine was not superior to that of its parent compound. Of the four statistical procedures examined, the sequential pairwise design appears to be best suited for comparing in vitro activity of an analogue and its parent compound and could result in a savings of both time and resources required for such comparisons.

Cell Survival↗
PubMed1984

Factors that influence growth of head and neck squamous carcinoma in the soft agar cloning assay.

A soft agar cloning assay was used to culture 158 specimens of head and neck tumors. Fifty-seven (36%) tumors were successfully cloned, 56 (35%) specimens failed to grow, and 45 (29%) were contaminated. There was no correlation of growth or cloning efficiency with the age of the patient, stage of the disease, degree of histologic differentiation, previous exposure to radiation therapy or chemotherapy, or subsequent survival. Sufficient cells were available to perform one to six (median, 2) chemosensitivity tests (total of 81) on specimens from 31 patients. Using 30% or less in vitro survival as the criterion for chemosensitivity, four patients were sensitive to one or more drugs. Only one of these patients received the same drug tested in vitro, and this tumor proved to be resistant. The cloning assay has not yet proved useful in predicting chemosensitivity in individual patients because of technical difficulties (low percentage of successful growth and high contamination rates).

Age Factors↗
PubMed1984

Southwest Oncology Group study of Mitoxantrone for treatment of patients with advanced squamous cell carcinoma of the head and neck.

Twenty-two patients are evaluable for response in a Phase II trial of Mitoxantrone for advanced squamous cell carcinoma of the head and neck. One patient had a partial response, one an improvement and twenty had progressive disease. The major toxicities were leukopenia and thrombocytopenia. There was no significant antitumor activity of Mitoxantrone in this group of patients with head and neck cancer, most of whom were previously treated with radiation and chemotherapy.

Adult↗
PubMed1984

Speech processing for cochlear implant prostheses.

The transformation of speech into electrical signals which can stimulate the auditory nerve in order to create hearing sensations that carry speech information depends on many factors. These include the limitations imposed by the current state-of-the-art in otological surgery, microelectronic and micromechanical technology, and knowledge of the functioning of the auditory system under both acoustic and electrical stimulation. Sufficient advances have been made in all these areas to enable several research centers to develop cochlear prostheses which give some hearing to certain totally deaf persons. The work of these centers towards the goal of full unaided speech perception via the prosthesis is examined and evaluated.

Adolescent↗
PubMed1984

Predictive value of trypan blue exclusion viability measurements for colony formation in a human tumor cloning assay.

Specimens (173) were evaluated to assess the predictive value of cell viability as measured by Trypan Blue exclusion on colony formation in a human tumor cloning system. Overall, there was no significant correlation between Trypan Blue exclusion-determined viability and colony formation in soft agar for these specimens (p = 0.43). This lack of significant correlation was maintained for primary, metastatic, solid, and fluid tumor specimens. These data suggest that, in this soft agar system, specimens containing cells with low Trypan Blue exclusion viability should not be excluded from testing, and that it may not be advantageous to plate on the basis of "viable cells" as measured by Trypan Blue exclusion.

Cell Survival↗
PubMed1984

Phase II trial of vindesine in patients with squamous cell cancer of the head and neck.

Fifteen patients with advanced squamous cell cancer of the head and neck received weekly vindesine at doses of 3 mg/m2. No patient had received prior chemotherapy, though all had received either radiotherapy or radiotherapy and surgery. Fourteen patients were evaluable for response. Two patients had documented partial remissions. Dose-limiting neutropenia was the primary toxic effect observed. It was frequent and occasionally life-threatening. Vindesine has minor but real activity in this group of patients with advanced head and neck cancer who have not received prior chemotherapy.

Aged↗
PubMed1984

Clinical trial of a multi-channel cochlear prosthesis: results on 10 postlingually deaf patients.

The clinical trial of a multi-channel cochlear prosthesis has been carried out on 10 profoundly-totally deaf adult patients. Speech perception tests have shown that all the patients received significant benefit from the device. They obtained improvements in understanding running speech from 47% to 550% when using the device in conjunction with lipreading compared to lipreading alone. With an open-set CID sentence test, three patients obtained scores showing an ability to understand speech without the need to lipread, and a further three patients had scores indicating they could also receive useful information without lipreading. In two patients, very limited open-set scores for electrical stimulation alone were obtained. This was most probably due to the fact that only a few channels of stimulation were possible due to cochlear disease, and they were therefore receiving information more like a single-channel device. The prosthesis has also been found to provide considerable help in hearing and recognizing everyday sounds.

Adult↗
PubMed1984

Underlying dimensions and individual differences in auditory, visual, and auditory-visual vowel perception by hearing-impaired children.

Vowel perception studies were conducted on a group of four adolescent children with congenital profound sensorineural hearing impairments in the three conditions of audition alone, vision alone, and audition plus vision. Data were analyzed using the ALSCAL multidimensional scaling procedure to identify the underlying dimensions and individual differences in dimension emphasis. The three dimensions obtained from the analysis of data for the audition alone condition were interpreted as the parameters of first and second formant frequencies, and vowel length. The one dimension for the vision alone condition was interpreted as the parameter of the width of the internal lip opening. The three dimensions for the audition plus vision condition were interpreted as the parameters of first formant frequency, vowel length, and the width of the internal lip opening. Subject variations in parameter preferences were observed for the audition alone and audition plus vision conditions but not for the vision alone condition.

Adolescent↗
PubMed1984

An acoustic model of a multiple-channel cochlear implant.

A set of bandpass filtered, pulsed noise stimuli presented to three normally hearing subjects was found to have psychophysical properties similar to those of a set of pulsed electrical stimuli presented to two cochlear implant patients. Identical procedures were used to compare the performances of the two groups of subjects in the following tasks: (a) pulse rate difference limen measurements, (b) pitch scaling for stimuli differing in pulse rate, (c) pitch scaling and categorization of stimuli differing in filter frequency or electrode position, and (d) similarity judgments of stimuli differing in pulse rate and filter frequency or electrode position. By choosing the parameters of the acoustic stimuli appropriately, a high level of agreement between the two sets of results was achieved. Electrical stimuli on electrodes at different sites in the cochlea were matched with pulsed noise passed through bandpass filters with different center frequencies. Matching was achieved for equal electrical and acoustic pulse rates.

Adult↗
PubMed1984

Speech processing studies using an acoustic model of a multiple-channel cochlear implant.

The speech perception of two multiple-channel cochlear implant patients was compared with that of three normally hearing listeners using an acoustic model of the implant for 22 different speech tests. The tests used included a minimal auditory capabilities battery, both closed-set and open-set word and sentence tests, speech tracking and a 12-consonant confusion study using nonsense syllables. The acoustic model represented electrical current pulses by bursts of noise and the effects of different electrodes were represented by using bandpass filters with different center frequencies. All subjects used a speech processor that coded the fundamental voicing frequency of speech as a pulse rate and the second formant frequency of speech as the electrode position in the cochlea, or the center frequency of the bandpass filter. Very good agreement was found for the two groups of subjects, indicating that the acoustic model is a useful tool for the development and evaluation of alternative cochlear implant speech processing strategies.

Aged↗
PubMed1984

Correlations between estrogen receptor, progesterone receptor, and patient characteristics in human breast cancer.

The relationships between estrogen receptor, progesterone receptor, and a variety of patient characteristics are described for 2,977 women with primary breast cancer. Older women were more likely to be estrogen-receptor positive than younger women. When patient age and menopausal status were analyzed together, age was found to be the primary determinant of increased estrogen-receptor concentrations. There appeared to be no relationship with progesterone receptor for either age or menopausal status when these variables were analyzed separately. But premenopausal women had higher progesterone receptor concentrations than postmenopausal women when patients of the same age were compared, perhaps reflecting greater estrogen-mediated synthesis of progesterone receptor. Tumor size was negatively related to steroid receptor concentrations, but no relationships were observed between steroid receptors and either the number of positive axillary lymph nodes or the location of the primary tumor.

Adult↗