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Biomedical subjects

G M Clark

Publications and source records attributed to G M Clark.

At least 361 records · Page 20Linked to original sources
PubMed1989

Implantation of the Melbourne/Cochlear multiple-electrode extracochlear prosthesis.

The Melbourne/Cochlear multiple-electrode extracochlear implant is designed for deaf patients who are unsuited to multiple-electrode intracochlear implantation. The implant consists of a receiver-stimulator package connected via a lead wire assembly to six individual stimulating electrodes. There is a choice of two alternative surgical procedures, both of which are via a combined middle ear approach using anterior and posterior tympanotomies. Four active electrodes shaped into compressible platinum-iridium soft-balls are fed through the mastoid cavity and across the facial recess, and placed into cavities that are made over the cochlear turns that project to the medial wall of the middle ear. One hard-ball active electrode is placed into the round window niche. One hard-ball reference electrode is placed into the hypotympanum. An additional electrode wrapped around the lead wire assembly can be used as an alternative reference electrode. A specially designed insertion needle facilitates the placement and the fixation of the soft-ball electrodes.

Cochlear Implants↗
PubMed1989

HER-2/neu oncogene protein and prognosis in breast cancer.

Amplification of the HER-2/neu oncogene was recently reported to predict poor clinical outcome in node-positive breast cancer patients. Since expression of the oncogene as its protein product might be even more closely related than gene amplification to disease progression, we have now examined levels of the HER-2/neu oncogene protein for its prognostic potential in both node-positive and node-negative breast cancer. Using Western blot analysis, levels of this protein were determined in 728 primary human breast tumor specimens. We examined relationships between this protein and other established markers of prognosis, as well as clinical outcome. In node-negative patients (n = 378), the HER-2/neu protein failed to predict disease outcome. However, in node-positive patients (n = 350), those patients with higher HER-2/neu protein had statistically shorter disease-free (P = .0014) and overall survival (P less than .0001) than patients with lower levels of the protein. Higher HER-2/neu protein was found in tumors without estrogen receptor (ER) (P = .02) or progesterone receptor (PgR) (P = .0003), and in patients with more than three positive lymph nodes (P = .04). A significant correlation between levels of the HER-2/neu gene protein and amplification of the gene itself was also found (n = 48, P less than .001). Multivariate analyses in these patients showed that the HER-2/neu protein is a significant independent predictor of both the disease-free and the overall survival in node-positive breast cancer, even when other prognostic factors are considered.

Antibody Specificity↗
PubMed1989

Speech perception using combinations of auditory, visual, and tactile information.

Four normally-hearing subjects were trained and tested with all combinations of a highly-degraded auditory input, a visual input via lipreading, and a tactile input using a multichannel electrotactile speech processor. The speech perception of the subjects was assessed with closed sets of vowels, consonants, and multisyllabic words; with open sets of words and sentences, and with speech tracking. When the visual input was added to any combination of other inputs, a significant improvement occurred for every test. Similarly, the auditory input produced a significant improvement for all tests except closed-set vowel recognition. The tactile input produced scores that were significantly greater than chance in isolation, but combined less effectively with the other modalities. The addition of the tactile input did produce significant improvements for vowel recognition in the auditory-tactile condition, for consonant recognition in the auditory-tactile and visual-tactile conditions, and in open-set word recognition in the visual-tactile condition. Information transmission analysis of the features of vowels and consonants indicated that the information from auditory and visual inputs were integrated much more effectively than information from the tactile input. The less effective combination might be due to lack of training with the tactile input, or to more fundamental limitations in the processing of multimodal stimuli.

Adult↗
PubMed1989

New biologic prognostic factors in breast cancer.

Long-accepted prognostic factors for breast cancer patients include the number of axillary lymph nodes positive for cancer; size of the primary; histopathologic features such as nuclear grade, histologic grade, and mitotic index; and the estrogen and progesterone receptor status. Unfortunately, these factors are relatively insensitive in predicting which women are particularly at risk of relapse. Newer discoveries which are or may be better prognosticators of a breast cancer patient's future course include growth factors, oncogenes, thymidine labeling index, and measurement of DNA ploidy status by flow cytometry.

Axilla↗
PubMed1988

Phase I clinical trial of carbetimer.

Carbetimer (carbethimer, N-137, NED-137, carboxyimamidate) is a low molecular weight polyelectrolyte with antitumor activity in a variety of tumor models. This phase I trial evaluated a single dose of carbetimer infused over 1-2 h every 28 days. Forty-three patients received 71 courses of the drug at doses ranging from 180 to 8500 mg/m2. The dose-limiting toxicity was hypercalcemia (serum calcium greater than 12.5 mg/dl) noted in two of three patients at a dose of 8500 mg/m2. Serum calcium levels between 10.5 and 12.5 mg/dl were noted in an additional three patients treated at doses greater than or equal to 1600 mg/m2. Calcium balance studies in three patients treated at 6500 mg/m2 revealed an increase in urinary cyclic AMP and phosphate excretion after treatment accompanied by a mild elevation of serum parathyroid hormone. Immunological studies in these patients revealed a statistically significant increase in the percentage of peripheral T-helper cells. An increase in the T-helper/suppressor cell ratio was observed in two of the three patients studied. Interleukin 2 production by phytohemagglutinin-stimulated peripheral mononuclear cells was increased in two of three patients. One patient with a renal cell carcinoma showed a mixed response. The recommended dose for phase II trials as assessed from this study is 6500 mg/m2 as a single dose every 28 days.

Adult↗
PubMed1988

Immunoreactive alpha transforming growth factor activity in effusions from cancer patients as a marker of tumor burden and patient prognosis.

alpha Transforming growth factors (alpha-TGFs) are polypeptides that stimulate anchorage-independent growth of various nontransformed cells in vitro and are believed to be involved in autocrine stimulation of tumor cells. alpha-TGF activity is secreted by a variety of human cancers leading to the possibility that it may serve as a tumor marker. alpha-TGF activity was measured in 130 effusions from patients with various types of cancer with a radioimmunoassay using sheep antibodies against the C-terminal 17 amino acids of linear rat alpha-TGF. Forty-two % of the effusions contained immunoreactive alpha transforming growth factor (Ir-alpha-TGF) activity, including 13 of 34 (38%) breast cancer, 12 of 24 (50%) lung cancer, and 13 of 31 (42%) ovarian cancer specimens. Concentrations ranged from 1.56 to 50 ng/ml. Only 3 of 17 control effusions from noncancer patients had low levels of activity, all less than 2 ng/ml. The presence of Ir-alpha-TGF activity correlated with patients' performance status (PS) and tumor burden. It was present in 18 of 67 (27%) effusions of patients with PS less than or equal to 2 and in 23 of 33 (70%) with PS 3 or 4 (P less than 0.0001). Only 2 of 43 (4%) patients with one site of metastatic disease had detectable Ir-alpha-TGF (mean, 0.23 ng/ml); 18 of 37 (48%) with two sites (mean, 5.22 ng/ml, P less than 0.0001); and 33 of 34 (97%) with greater than two sites (mean, 5.93 ng/ml, P = 0.002). It was present in a larger percentage of effusions from breast cancer patients with estrogen- and progesterone receptor-negative tumors. Univariate analysis revealed that detectable Ir-alpha-TGF activity, PS 3 or 4, and the number of sites of disease correlated with a shorter survival. Only Ir-alpha-TGF and PS 3 or 4 retained significance in a multivariate analysis. In conclusion, Ir-alpha-TGF is frequently detectable in effusions from cancer patients, it correlates with other known adverse prognostic factors, and its presence predicts for a poor survival. Further studies of alpha-TGF activity in more readily accessible body fluids such as serum or urine are warranted.

Ascitic Fluid↗
PubMed1988

Determination of transforming growth factor activity in effusions from cancer patients.

Transforming growth factors (TGF) are polypeptides that stimulate anchorage-independent growth of various nontransformed cells in vitro. Transforming growth factors have been found in tumor extracts and in the urine of cancer patients. The specific questions of our study were whether TGF activity can be detected in malignant effusions, how different assays for TGF correlate with each other, and how assays for TGF correlate with soft agar tumor colony formation as measured by the human tumor cloning assay (HTCA). The TGF activity was measured by a normal rat kidney transformation assay (NRKA), a 125I-EGF radioreceptor assay (RRA), and a radioimmunoassay (RIA) for TGF-alpha. Cells from effusions were cytologically examined and plated in the HTCA. A total of 104 effusions from cancer patients and 17 effusions from non-cancer patients was tested. Transforming growth factor activity was detected in some specimens. Only the TGF-alpha RIA and the HTCA showed significant differences between cancer and noncancer patients. Immunoreactive TGF-alpha was measurable in some cases by RIA even when cytologic testing failed to detect malignant cells. Spearman correlations between assays indicated that RIA results correlate significantly with all other assays. It is concluded that TGF-alpha activity might be important for in vitro colony formation of human tumor cells.

Ascitic Fluid↗
PubMed1988

DNA flow cytometry and prognostic factors in 1331 frozen breast cancer specimens.

Breast cancer proliferative capacity as determined by the DNA thymidine labeling index, along with estrogen and progesterone receptor status, is highly predictive for risk of relapse and overall survival. Recently, DNA ploidy and proliferative capacity (S-phase fraction [SPF]) as determined by flow cytometry have also shown significant prognostic value. The authors have developed a technique which allows a 50 to 100 mg aliquot of the same frozen breast tumor specimen routinely employed in steroid receptor assays, to be assayed for both DNA ploidy and SPF by flow cytometry. Of the 1331 tumors examined, DNA histograms were evaluable for ploidy in 89% (1184) of specimens examined; 57% of these were aneuploid. Adapting a trapezoidal model to estimate SPF in both diploid and aneuploid tumors, the authors found 81% (1084) to be evaluable for SPF, with a median SPF of 5.8% for the entire population. The median SPF was significantly lower in diploid tumors (2.6%) than in aneuploid tumors (10.3%, P less than 0.0001). Both aneuploidy and high SPF were strongly associated with absence of steroid receptors. Aneuploid tumors showed more striking differences in the frequency of high S-phase values with respect to receptor status and age or menopausal status, whereas diploid but not aneuploid tumors showed lower SPF in node-negative versus node-positive patients. Because it is particularly important to identify the high-risk minority of node-negative patients, the authors examined the node-negative group separately. High SPF subgroups appeared in each category of receptor status and age or menopausal status within the node-negative group, suggesting that SPF will be an independent prognostic factor. With the DNA flow cytometric methods used here, it is now practical to determine ploidy and SPF for nearly every breast cancer patient. These factors, which show associations with established prognostic factors, such as receptor status can now be fully evaluated for their prognostic significance in broad patient populations.

Aneuploidy↗
PubMed1988

Application of a new preclinical drug screening system for cancer of the large bowel.

We report a prospective evaluation of three human, continuous colorectal cancer cell lines and a new semiautomated radiometric technique (Bactec system) as a primary screening procedure for cytotoxic compounds with activity against cancer of the large bowel. COLO 320DM, Ht-29, and the metastatic OM-1 colon cancer cell line that have previously been shown to yield clinically relevant information in terms of drug sensitivity patterns in humans were all tested against 11 new compounds currently being investigated in phase I or early phase II clinical trials. Our results suggest that trimetrexate, DUP-785, didemnin B, and flavone-8-acetic acid may be clinically effective for the treatment of colorectal cancer.

Colonic Neoplasms↗
PubMed1988

Effects of prednisolone on sex hormone binding globulin during primary endocrine treatment of advanced breast cancer.

Serum sex hormone binding globulin (SHBG) was measured in 21 pre and 39 postmenopausal women with advanced breast cancer before treatment and 1, 3, 6, 9 and 12 months after ovarian irradiation or during continuous administration of tamoxifen at a dose of 10 mg twice daily, respectively; some patients received additional prednisolone at a dose of 5 mg twice a day. Ovarian irradiation was associated with a 25% reduction in serum SHBG levels 3 to 6 months after treatment whilst patients on tamoxifen experienced a rise of about 80% in serum SHBG levels after 1 to 3 months. In postmenopausal women prednisolone markedly dampened the effect of tamoxifen, reducing a 80% rise to about 20%. There was no relationship between SHBG levels and response to treatment.

Breast Neoplasms↗
PubMed1988

Cytotoxic activity of 9-beta-D-arabinofuranosyl-2-fluoroadenine 5-monophosphate (fludarabine, NSC 312887) in a human tumor cloning system.

A human tumor cloning system was utilized to screen for in vitro antitumor effects of the new purine antimetabolite 9-beta-D-arabinofuranosyl-2-fluoroadenine 5-monophosphate. Two hundred and thirty-one specimens were evaluable for drug sensitivity information (i.e. greater than or equal to 20 colonies on control plates). The overall in vitro response rates (defined as a less than or equal to 50% survival of tumor colony forming units) at two different concentrations of the new drug (0.1; 1.0 micrograms/ml) were between 21 and 24%. The new drug had significant antitumor activity (i.e. in more than 35% of specimens of those with at least five tested specimens) only against non-Hodgkin's lymphoma and breast cancer.

Antimetabolites, Antineoplastic↗
PubMed1988

The surgical anatomy for multiple-electrode extracochlear implant operations.

Direct access to the whole length of the cochlear turns via endaural middle ear approach for the placement of extracochlear electrodes is severely restricted. Approximately 10 mm. of the cochlear turns are accessible, being less than a third of their length. The middle cranial fossa, the facial nerve, the internal carotid artery and the temporomandibular joint restrict the access. A further restriction is caused by the position of the cochlea and the direction of its axis. The anterior part of the cochlea lies anterior to the tympanic membrane and medial to the temporomandibular joint, thus limiting an endaural approach to a postero-lateral direction. Despite this limitation small sections of the basal, middle and apical turns of the cochlea can be reached.

Cochlea↗
PubMed1988

Underlying structure of auditory-visual consonant perception by hearing-impaired children and the influences of syllabic compression.

The identification of consonants in (a)-C-(a) nonsense syllables, using a fourteen-alternative forced-choice procedure, was examined in 4 profoundly hearing-impaired children under five conditions: audition alone using hearing aids in free-field (A), vision alone (V), auditory-visual using hearing aids in free-field (AV1), auditory-visual with linear amplification (AV2), and auditory-visual with syllabic compression (AV3). In the AV2 and AV3 conditions, acoustic signals were binaurally presented by magnetic or acoustic coupling to the subjects' hearing aids. The syllabic compressor had a compression ratio of 10:1, and attack and release times were 1.2 ms and 60 ms. The confusion matrices were subjected to two analysis methods: hierarchical clustering and information transmission analysis using articulatory features. The same general conclusions were drawn on the basis of results obtained from either analysis method. The results indicated better performance in the V condition than in the A condition. In the three AV conditions, the subjects predominantly combined the acoustic parameter of voicing with the visual signal. No consistent differences were recorded across the three AV conditions. Syllabic compression did not, therefore, appear to have a significant influence on AV perception for these children. A high degree of subject variability was recorded for the A and three AV conditions, but not for the V condition.

Adolescent↗
PubMed1988

Phonemic information transmitted by a multichannel electrotactile speech processor.

A wearable electrotactile speech processor was evaluated in a study with seven normally hearing and four hearing-impaired subjects. The processor estimated the fundamental frequency, the second-formant frequency, and amplitude of the acoustic speech signal. These parameters were presented as a pattern of electrical pulses applied to eight electrodes positioned over the digital nerve bundles on one hand. The device was shown to provide useful information for the recognition of phonemes in closed sets of words using tactile information alone. The device also supplemented lipreading to improve the recognition of open-set words. The recognition of duration and first- and second-formant frequencies of vowels and the recognition of voicing and manner of consonants were improved over recognition with lipreading alone. Recognition of final consonants was improved more than recognition of initial consonants. These results indicate that the device may be useful to both severely and profoundly hearing-impaired people.

Adult↗
PubMed1988

The binding of blood-borne estrogens in normal vegetarian and omnivorous women and the risk of breast cancer.

Serial blood samples were taken at two-hour intervals over a 24-hour period from 25 premenopausal vegetarians (12 vegans and 13 ovolactovegetarians) and from 21 omnivorous controls. All members of the former group had been on a vegetarian diet for a minimum of three years. The mean proportion of estradiol unbound to blood proteins was similar in both vegetarians (1.26%) and meat eaters (1.16%). However, the amount bound to albumin was significantly raised in vegetarians (50.1% vs. 43.1%, p less than 0.009), whereas that bound to sex hormone-binding globulin (SHBG) was correspondingly lower (48.7% vs. 55.8%, p = 0.01). Mean levels of SHBG were similar in vegetarians (59.9 nmole/l) and omnivores (62.0 nmole/l), as was the total amount of free fatty acid (0.42 mmole/l for both). Within the vegetarian group, no differences were detected between vegans and ovolactovegetarians.

Adult↗
PubMed1988

Steroid receptors, cellular kinetics, and lymph node status as prognostic factors in breast cancer.

Steroid receptor status, cellular kinetics, abnormal proto-oncogene presence, and lymph node metastases all have been shown to provide prognostic information in breast cancer. The factors guide the choice of therapy and predict the course of the disease. Both disease-free survival and overall survival are predicted by these variables. Steroid receptors are the most reliable predictor of hormonal responsiveness. Lymph node involvement is crucial in determining the extent of the disease and the need for adjuvant therapy. Cellular kinetics and abnormal proto-oncogene presence predict tumor aggressiveness. Together these prognostic factors provide considerable information to the clinician.

Breast Neoplasms↗