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Biomedical subjects

G M Clark

Publications and source records attributed to G M Clark.

At least 451 records · Page 25Linked to original sources
PubMed1984

Implanted material tolerance studies for a multiple-channel cochlear prosthesis.

We have performed a number of temporal bone and animal studies in order to evaluate the histopathological effects of intracochlear electrode implantation and chronic electrical stimulation. Our results indicate that (a) the insertion of a free-fit scala tympani array results in minimal damage to the membranous labyrinth; (b) the materials used in the electrode array evoke mild tissue reactions when implanted subcutaneously, in muscle, or within the scala tympani; (c) intracochlear electrical stimulation for periods of 500 to 2000 hours, using carefully controlled biphasic pulses, does not adversely affect the population or neural activity of the primary auditory neurones; (d) labyrinthine infection severely reduces the number of viable spiral ganglion cells; (e) an adequate fibrous tissue seal of the round window can prevent the spread of infection from the bulla to the implanted cochlea in cats, following inoculation of the bulla cavity with bacteria; (f) bone growth is not associated with electrical stimulation per se; (g) the electrode arrays show minimal platinum dissolution and no apparent degradation of the Silastic carrier following periods of long-term intracochlear electrical stimulation.

Animals↗
PubMed1984

Interaction of oxygen-carrying resuscitation fluids with morphine.

The oxygen-carrying resuscitation fluids, Fluosol DA 20% and stroma-free hemoglobin, are currently being evaluated for efficacy and effects in vivo. Because these fluids may be administered to trauma victims, the pharmacokinetics of morphine was studied in rats after transfusion with one of these fluids. During development of high-performance liquid chromatography assay for morphine in plasma, an in vitro interaction between plasma, Fluosol DA, or stroma-free hemoglobin and morphine was observed at pH greater than 10.5. This interaction was dependent on pH and was specific to morphine, compared with codeine. The interaction between stroma-free hemoglobin and morphine appeared to be covalent in nature. The t1/2 of morphine was significantly prolonged from 1.02 +/- 0.50 hours (mean +/- SD) to 2.46 +/- 2.68 hours (p = 0.03) after transfusion with stroma-free hemoglobin, and to 2.05 +/- 0.95 hours (p = 0.006) after transfusion with Fluosol DA. The volume of distribution was increased from 1.35 +/- 0.81 L X kg-1 to 2.99 +/- 1.45 L X kg-1 (p = 0.004) after transfusion with stroma-free hemoglobin; no such difference was observed after transfusion with fluosol DA (p = 0.86). The area under the time-concentration curve was increased from 2.37 +/- 1.78 mg X hr X L-1 to 6.02 +/- 6.61 mg X hr X L-1 (p = 0.02), and total body clearance was decreased from 1.02 +/- 0.53 L X hr-1 X kg-1 to 0.55 +/- 0.36 L X hr-1 X kg-1 (p = 0.01) after transfusion with Fluosol DA. No significant differences were observed in these parameters after transfusion with stroma-free hemoglobin (p = 0.48 and p = 0.81, respectively). These data show that stroma-free hemoglobin prolongs the t1/2 of morphine by altering the volume of distribution. In contrast, Fluosol DA prolongs the t1/2 of morphine by altering the total body clearance. These data may have important therapeutic implications.

Animals↗
PubMed1984

A signal processor for a multiple-electrode hearing prosthesis.

A 22-electrode implantable hearing prosthesis uses a wearable speech processor which estimates three speech signal parameters. These are voice pitch, second formant frequency and flattened spectrum amplitude. The signal is monitored continuously for periodicity in the range 80-400 Hz and, if this is present, stimulation occurs at the same rate. Otherwise, as in the case of unvoiced sounds, it occurs at the random rate of fluctuation of the signal envelope. The second formant is obtained by filtering to extract the dominant peak in the midband region and by continuous measurement of the zero crossing rate. The amplitude measured is that of the whole speech spectrum, pre-emphasized by differentiation. The values that are presented to the patient are the parameter estimates immediately prior to the stimulation pulse. Second formant frequency is coded by selection of an appropriate electrode in the cochlea and amplitude by a suitably controlled current. Automatic gain control is used to keep the dynamic range of the amplitude estimate within the 30 dB range of the circuitry.

Cochlear Implants↗
PubMed1984

Clinical results using a multiple-channel cochlear prosthesis.

A total of eight profoundly deaf patients have been implanted with the Nucleus Limited multiple-channel cochlear prosthesis at the University of Melbourne since it became available in late 1982. All patients are everyday users of the device. Speech testing using the device alone has shown consistently high scores for a variety of closed set tests and significant levels of open set speech understanding in most of the patients. Lipreading assessment with phoneme, word, sentence and speech tracking material shows significant improvement when using the prosthesis for all patients tested. Other benefits reported are recognition of environmental sounds, decrease in tinnitus, increased confidence in social and vocational situations and improved voice control. One patient is able to cope with interactive conversations over the telephone and three others are able to use the telephone in a limited way without special codes.

Adult↗
PubMed1984

Multiple progesterone receptor assays in human breast cancer.

A review of assay results from more than 5500 patients revealed 283 patients in whom multiple breast cancer specimens were analyzed for progesterone receptor (PGR). All assays were performed in a single laboratory between 1975 and 1982 using the sucrose gradient technique. We considered only the 8S fraction of PGR. Simultaneous assays in 109 patients yielded 14% discordance [one assay with greater than 10 fmol/mg cytosol protein (PGR+) and one assay with less than 5 fmol/mg protein (PGR-)]. Among 161 sequential assays, there was an overall discordance of 19%: 8% (nine of 106) when the initial assay was PGR-, but 44% (24 of 55) when the initial assay was PGR+. Among PGR+ patients initially assayed at the time of diagnosis, there was a tendency to greater receptor loss in patients with positive axillary lymph nodes (44 versus 11%). The length of time between biopsies did not increase the discordance, but endocrine therapy within this interval did increase it (56% of initially PGR+ patients who received interim endocrine therapy were PGR- at second biopsy). to evaluate the significance of interval loss of PGR, we compared survival from first biopsy in initially PGR+ patients who subsequently lost their receptor versus those whose receptor persisted. The latter group experienced a significantly longer survival (p less than 0.02). In summary, we observed an ominous loss of PGR in sequential biopsies, particularly with intervening endocrine therapy, and those patients whose tumor cells lost PGR experienced poorer survival than did patients retaining PGR. Therefore, patients with PGR+ primary tumors require repeat biopsy for PGR upon disease recurrence for optimal treatment planning.

Biopsy↗
PubMed1983

Progesterone receptors as a prognostic factor in Stage II breast cancer.

The presence of estrogen receptors in breast cancers is now accepted as a predictor of extended disease-free survival, but the relative value of progesterone receptors for this purpose has not been established. We have examined both receptors along with other risk factors in 189 patients receiving adjuvant therapy for Stage II breast cancer. The presence of either estrogen receptors or progesterone receptors was positively correlated with disease-free survival when analyzed separately, whether or not the adjuvant regimen included an endocrine component. However, when estrogen receptors and progesterone receptors were analyzed together in multivariate models, the presence of progesterone receptors was more significant than that of estrogen receptors for predicting time to recurrence, regardless of what other variables were included in the model. These data suggest that determination of the progesterone-receptor concentration is of equal or greater value than determination of the estrogen-receptor concentration for predicting the disease-free survival of patients with breast cancer. Future trials should include measurement of progesterone receptors.

Breast Neoplasms↗
PubMed1983

Clinical trial of a multiple-channel cochlear prosthesis. An initial study in four patients with profound total hearing loss.

The clinical trial of a multiple-channel cochlear prosthesis was undertaken in four patients with postlingual deafness and profound total hearing loss. The results of open-set speech tests confirmed that, using electrical stimulation alone, one patient could have a meaningful conversation without resorting to lipreading (for example, this patient uses the prosthesis to converse with her husband on the telephone). The results of closed-set speech tests also suggested that a multiple-channel stimulator is more effective than a single-channel one in conveying speech information. The cochlear prosthesis was especially effective in all four patients when it was used in conjunction with lipreading, and speech-tracking tests showed that the patients could combine the information obtained from both electrical stimulation and lipreading.

Adult↗
PubMed1983

Two-component hearing sensations produced by two-electrode stimulation in the cochlea of a deaf patient.

Dissimilarities in perception elicited by stimulation with two electrodes were estimated. A two-dimensional spatial configuration was found to be suitable to represent the dissimilarity data, and the two dimensions could be interpreted as corresponding to the position of the apical and basal electrode of the two-electrode combination. A speech-processing strategy that converts acoustic, first and second formants to two-electrode stimulation is proposed.

Cochlea↗
PubMed1983

Comparative cytotoxicity of adriamycin, mitoxantrone and bisantrene as measured by a human tumor cloning system.

A human tumor cloning system was used to assess the cytotoxicity of adriamycin, mitoxantrone and bisantrene at concentrations that are equitoxic in man. There were 989 specimens evaluable for drug sensitivity analysis. Overall, adriamycin showed in vitro cytotoxicity (greater than or equal to 50% decrease in tumor colony forming units) 14% of the time; mitoxantrone, 21% of the time; and bisantrene, 31% of the time. Three hundred ninety-nine of these evaluable specimens were simultaneously tested against more than one of the agents, providing 631 two-way drug comparisons. For these comparisons, there was lack of co-resistance 27-34% of the time, with mitoxantrone being more active than adriamycin (p less than .05) and bisantrene being more active than adriamycin (p less than .01) or mitoxantrone (p less than .01). These data suggest that comparative and sequential clinical use of these agents should be investigated.

Anthracenes↗
PubMed1983

Progesterone receptors and 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 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 the end product of estrogen action. We have examined the relationship between progesterone receptor and response of advanced breast cancer tumors to hormonal manipulations. Promising retrospective results indicate the need for new, prospective clinical trials to further define the prognostic value of progesterone receptor for these tumors. We have also analyzed the disease-free intervals of patients with primary disease and found that progesterone receptor was 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, and that the results of these assays will help the physician individualize therapy for breast cancer patients.

Breast Neoplasms↗
PubMed1983

Prognostic factors in primary breast cancer.

Estrogen receptor (ER) has been well documented as an important predictor of long disease-free intervals and survival for patients with primary breast cancer (1). In advanced breast cancer it has been hypothesized that the presence of progesterone receptor (PR) might be a more sensitive marker for predicting response to endocrine therapy (2, 3). We have recently found that PR was more important than ER in predicting disease-free survival for a group of patients with stage-II breast disease that was treated according to a randomized protocol (Clark et al., submitted for publication). This report examines the generality of that result by extending our analysis to include patients from other institutions. The additional patients were not treated according to a rigid clinical protocol, but rather received treatments in much the same way as the majority of breast cancer patients in a community practice. Of interest was whether the relationship between steroid receptors and disease-free survival that we have previously reported would hold with this new group of patients with different demographic and treatment profiles. The relationships between steroid receptor levels and both disease-free and overall survival were examined in detail.

Antineoplastic Combined Chemotherapy Protocols↗