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Biomedical subjects

G M Clark

Publications and source records attributed to G M Clark.

At least 415 records · Page 23Linked to original sources
PubMed1986

Selection of chemotherapy for patient treatment utilizing a radiometric versus a cloning system.

From the 1950s to the 1970s, a number of in vitro systems that measured inhibition of glucose metabolism were used to predict the responsiveness of patients' tumors to chemotherapy. In vitro-in vivo correlations were excellent, with true positive predictions ranging from 68% to 96% and true negative predictions of 95% to 100%. The radiometric system is a new in vitro technique that measures the conversion of 14C-glucose to 14CO2. The system already has been utilized to screen prospective new antineoplastic agents for cytotoxicity. The present study was undertaken to determine if the radiometric system might be used to predict correctly the responsiveness of an individual patient's tumor to single-agent or combination-agent chemotherapy. Fifty-six tumor specimens were divided and tested for drug sensitivity in the radiometric system and a conventional human tumor clonning system. Overall, there was a significant correlation between in vitro and in vivo results for the conventional cloning system (P = 0.03). However, there was no significant relationship between in vitro and in vivo results for the radiometric system. The radiometric system consistently failed to predict the tumor's clinical sensitivity to single agents. A radiometric system is not useful in predicting the responsiveness of a patient's tumor to single agent chemotherapy and is not a replacement for the more biologically attractive human tumor cloning system.

Antineoplastic Agents↗
PubMed1986

In vitro activity of the novel antitumor antibiotic fostriecin (CI-920) in a human tumor cloning assay.

A human tumor cloning assay was utilized to evaluate the antineoplastic activity of the novel antitumor antibiotic fostriecin (CI-920). Initial screening with 10.0 mcg/ml continuous exposure against a variety of histologic tumor types resulted in 14/51 (27%) in vitro responses (defined as greater than 50% decrease in TCFUs). Further investigation of the compound was performed in 1-hr preincubation experiments. The in vitro response rate at a concentration of 1.0 mcg/ml (which was considered to correspond to a clinically achievable concentration) was 15/43 (35%). Response rates for specific tumor types included: 5/15 in ovarian cancer, 5/12 in breast, and 4/11 in human lung cancer. The impression of significant antitumor activity of the compound at this dose was further substantiated by comparing its in vitro activity with a variety of simultaneously tested standard anticancer agents. In addition, these data indicated the possibility of non-cross resistance of CI-920 to several established cytostatics. CI-920 is a compound with good in vitro activity which should be further developed for clinical trials.

Alkenes↗
PubMed1986

Salivary oestradiol and progesterone levels in premenopausal women with breast cancer.

The concentrations of oestradiol and progesterone have been measured in salivary specimens collected daily over a complete menstrual cycle in 12 patients with operable breast cancer and 12 normal control volunteers. There was no significant difference (P greater than 0.05) for either hormone between these two groups. Both showed a mid-cycle rise in oestradiol levels followed by a smaller but sustained increase during the luteal phase. The progesterone concentration increased markedly during the luteal phase of the cycle. Total or non-protein bound oestradiol levels measured in blood samples from 19 normal women were both linearly correlated (P less than 0.001) with the concentration of oestradiol in matched saliva samples. The amount of free oestradiol in blood was about twice that found in saliva.

Adult↗
PubMed1986

Loudness summation, masking, and temporal interaction for sensations produced by electric stimulation of two sites in the human cochlea.

Three psychophysical studies were conducted on two multichannel cochlear implant patients. The first study investigated the amount of loudness summation as a function of the spatial separation between two bipolar electrode pairs in the cochlea. Summation was found to increase in an orderly way with the separation between the two electrode pairs. This observation suggested that loudness was related to the distribution of discharge rate of auditory neurons along the cochlea for electric stimulation, and a model of loudness summation formulated on the basis of a functional relationship between loudness and the discharge rate distribution was proposed. The second study investigated the possibility of estimating the discharge rate distribution by means of masking. The amount of masking was found to decrease in an orderly fashion with the spatial separation between the masker and probe electrode pairs. This pattern of masking is consistent with the physiological and modeling observation that the current and neural discharge rate distributions produced by an electrode pair (masker) in the cochlea are approximately bell shaped with gradually decaying borders. The third study investigated the just-discriminable changes in the temporal delay between two interleaving pulse trains delivered, respectively, to two electrode pairs in the cochlea. Discrimination performance was found to decrease with the spatial separation between the two electrode pairs.

Cochlea↗
PubMed1986

Use of in vitro dose response effects to select antineoplastics for high-dose or regional administration regimens.

Several preclinical and clinical studies have documented that dose or dose intensity of chemotherapeutic agents are important factors for response of patients' tumors. This finding has prompted empiric trials of certain chemotherapeutic agents in high-dose or regional administration treatment regimens. The present study was performed to identify agents that would be particularly good candidates for high-dose or regional administration regimens against particular types of tumors. Using a human tumor cloning technique, we constructed dose in vitro response lines for ten different chemotherapeutic agents against seven different histologic types of malignancies. Slopes of the lines indicated the agents with the greatest increases of in vitro response per increment in dose of the agent. Tumors against which the agents gave the steepest dose response lines included lymphoma, head and neck cancer, ovarian cancer, and small-cell lung cancer, while the dose response lines for non-small-cell lung cancer, breast cancer, and colon cancer were quite flat. Suggestions for clinical trials based on these findings include the use of high-dose melphalan for patients with lymphoma, head and neck, and ovarian cancer; the use of mitoxantrone in high-dose regimens for patients with breast cancer; high-dose cisplatin regimens for patients with small-cell lung cancer; high-dose bleomycin regimens for patients with non-small-cell lung and head and neck cancer; and regional perfusion of liver metastases from colorectal cancer with cisplatin. Prospective testing of high-dose or regional administration regimens suggested by this new model should indicate its use for prediction of the best agent to use in high-dose regimens against a particular tumor type.

Antineoplastic Agents↗
PubMed1986

New screening system for selection of anticancer drugs for treatment of human colorectal cancer.

We report an evaluation of a new radiometric technique (BACTEC assay) as a potential screening system for cytotoxic compounds with activity against cancer of the large bowel. Exponentially growing cells of nine different human colorectal cancer cell lines were exposed to a variety of standard anticancer agents with or without documented clinical activity. Each drug was tested in a series of 1-h and continuous exposure studies utilizing three different concentrations. Antineoplastic effects were analyzed as a function of in vivo achievable serum concentrations, namely by a ratio of the concentration required to decrease cell growth to 10% of control to one-tenth of the peak plasma concentration in humans. Our results suggest that COLO 320DM, OM-1, and Ht-29 cells manifest responsiveness to anticancer drugs consistent with that noted in clinical studies with most agents tested. The radiometric technique provides several advantages for a screening system, including reproducibility, a good agreement with the cloning assay, speed, and low costs. The combined use of the BACTEC technique and the three colon cancer cell lines could prove useful as a screen for new anticancer compounds with activity in colorectal cancer.

Antineoplastic Agents↗
PubMed1986

Identification of women at high risk of breast cancer.

Prospective studies of risk factors for breast cancer have been carried out since 1961 on a normal population which now comprises some 15,000 women. Classical (anamnestic) factors such as ages at menarche, menopause, or at first child, post-menopausal weight and high parity are not strong determinants of risk. Measurements of various aspects of endocrine function are more successful in identifying women at risk, as is assessment of mammographic parenchymal patterns but, again, these variables are not effective enough to make an intervention strategy imperative. However, the combination of classical, endocrinological, and radiological factors appears to achieve this aim. A substantial sub-set of women who have a four-fold risk of breast cancer may be identifiable.

Adult↗
PubMed1986

Role of steroid hormone receptors as prognostic factors in primary breast cancer.

A review and update of published studies on estrogen receptor (ER) and progesterone receptor (PgR) as prognostic factors in breast cancer support the following conclusions. In stage I breast cancer, the lack of ER seems to be the most important factor for predicting earlier recurrence and poorer survival. In stage II breast cancer, PgR content appears to be better than ER content in predicting disease-free survival and PgR content is as important as ER content in predicting overall survival. The benefits of adjuvant endocrine therapy are better predicted by the presence or absence of PgR than by the presence or absence of ER. Measurement of proliferative activity (S-phase DNA) by thymidine labeling or flow cytometry and of aneuploidy by flow cytometry also provides prognostic information. The strong correlations between tumor receptor content, percent S-phase cells, and aneuploidy suggest that these measurements in concert might identify a subset of stage I breast cancer patients at increased risk for recurrence, who would thus be potential candidates for adjuvant therapy.

Adult↗
PubMed1986

Model for estimation of clinically achievable plasma concentrations for investigational anticancer drugs in man.

A major problem related to in vitro testing of new investigational anticancer compounds is the lack of accurate pharmacokinetic data for the drugs in man. Based on the concept of a relationship between certain toxicologic endpoints in animal systems and maximally tolerated doses in man, we hypothesized that a comparable agreement might exist between these experimental animal toxicology data and clinically achievable peak plasma concentrations (PPCs). A retrospective analysis of the known data pairs of 28 commonly used cytotoxic compounds supports the existence of a reasonably good correlation between ip LD50 values (Pearson test) in nontumored mice and PPCs in man (r2 = 0.501; P less than 0.0001). Our data suggest that by use of the resultant statistical regression model a rational starting point can be selected for in vitro screening of entirely new agents for which human PPCs are not available. Additionally, application of this approach may also prove useful in relation to selecting in vitro doses for chemosensitivity assays intended for predictive correlation with clinical response in cancer patients.

Animals↗
PubMed1985

Scanning electron microscopy of chronically stimulated platinum intracochlear electrodes.

Platinum electrodes were examined for evidence of corrosion using a scanning electron microscope (SEM). In vivo electrodes, stimulated using charge-balanced biphasic pulses for periods of up to 2000 h at charge densities of 0.18-0.32 microC mm-2 geom. per phase, were compared with in vitro electrodes stimulated in inorganic saline using similar stimulus parameters, and with in vivo control electrodes. The in vitro stimulated electrodes showed evidence of platinum corrosion at high charge density and aggregate charge injection. Significantly, the in vivo stimulated electrodes showed no evidence of stimulus induced corrosion. Indeed, their surfaces were similar to the in vivo control electrodes. In vitro electrochemical studies have demonstrated that proteins play a significant role in the inhibition of platinum dissolution: the present study has demonstrated an inhibitory effect in vivo. This may be due to the presence of proteins.

Animals↗
PubMed1985

Progressive ototoxicity of neomycin monitored using derived brainstem response audiometry.

Progressive hearing loss following the systemic administration of neomycin was investigated using derived brainstem response audiometry. Cats were given three to five times the maximum recommended clinical dose of neomycin over a period of 10 days. Their hearing was monitored prior to and during the administration of the drug, and periodically following its completion. The results of this study showed that the induced hearing loss generally proceeded from high to low frequencies as an advancing lesion, with regions apical to the lesion functioning normally. Although considerable variability in response to the drug existed among animals, the evoked responses from both ears of each animal showed close bilateral symmetry during the deafening process. Furthermore, the present results highlight the long-term ongoing ototoxicity associated with neomycin, and the importance of monitoring high frequencies for initial signs of an aminoglycoside induced hearing loss.

Animals↗
PubMed1985

Current distributions in the cat cochlea: a modelling and electrophysiological study.

The current distribution of bipolar electrodes implanted into the scala tympani of the cat cochlea was investigated using a two-electrode masking technique. Two electrode masking is a non-invasive technique which requires two electrically independent electrodes and relies upon the forward masking of the electrically evoked brainstem response to a probe stimulus by that of a preceding test stimulus. The technique was described in terms of a model, which enabled an approach for estimating the scala tympani length constant to be established. Model results have shown good agreement with electrophysiological results. Application of the model confirmed the scala tympani length constant within the basal turn of the cochlea to lie between 3 and 4 mm.

Animals↗
PubMed1985

Telephone use by a multi-channel cochlear implant patient. An evaluation using open-set CID sentences.

A totally deaf person with a multiple-channel cochlear prosthesis obtained open-set speech discrimination using the telephone. CID Everyday Sentences were presented by telephone to the patient, who repeated an average of 21 per cent of key words correctly on the first presentation, and 47 per cent when a repeat of the sentences was permitted. This result is consistent with the patient's reports of telephone usage.

Adult↗
PubMed1985

Absolute identification of electric pulse rates and electrode positions by cochlear implant patients.

In a single interval task, multichannel cochlear implant patients were asked to identify the members of a set of seven electric stimuli differing in electric pulse rate or electrode position. The perceptual sensitivity index (d') between successive stimuli in a stimulus set was calculated from the confusions among the seven stimuli. The results showed that the pulse rate above which the identification task became difficult varied from 200 to 600 pps from patient to patient. For the identification of the positions of seven bipolar electrode pairs, d' measures for stimulus sets differing in spatial separation or spatial extent were compared. Spatial separation is defined as the fixed distance between the two basal (or apical) electrodes of two successive bipolar electrode pairs in a stimulus set, while spatial extent is defined as the fixed distance between the apical and basal electrodes of each bipolar electrode pair in a stimulus set. The results showed that perceptual performance improved in an orderly way with spatial separation, but was not significantly affected by spatial extent.

Adult↗
PubMed1985

A wearable multiple-electrode electrotactile speech processor for the profoundly deaf.

A versatile, battery-powered device for the representation of speech information as patterns of tactile stimulation has been developed. The features of this device that are different from other electrotactile speech processors are the site of stimulation, the proposed strategy for the representation of speech information, and the small size of the device.

Communication Devices for People with Disabilities↗