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Biomedical subjects

G M Clark

Publications and source records attributed to G M Clark.

At least 199 records · Page 11Linked to original sources
PubMed1995

Chronic middle ear disease and cochlear implantation.

We have presented three patients with bilateral CSOM who were otherwise suitable for cochlear implantation. These patients had conventional surgical management of CSOM and were implanted after a period of 6 months through apparently healthy middle ears. However, all three had a recurrence of middle ear disease requiring further surgery, and one had a potentially life-threatening complication necessitating removal of the implant. Before considering cochlear implantation in patients with bilateral CSOM, it is essential to eradicate all disease, and radical mastoidectomy with obliteration may be necessary. The use of a cochlear sealing device may further ensure prevention of infection spreading into the cochlea.

Aged↗
PubMed1995

Investigations on a curved intracochlear array.

A curved electrode array and inserting tool have been developed at the University of Melbourne. This electrode array can be successfully implanted with few modifications to the surgical procedure presently in use. When implanted, the curved electrode array adopts a position closer to the modiolus than does the standard straight electrode array.

Cochlear Implants↗
PubMed1995

Initial investigation of the efficacy and biosafety of sodium hyaluronate (Healon) as an aid to electrode array insertion.

Sodium hyaluronate has potential uses as an electrode lubricant in cochlear implant surgery. Deeper electrode insertions were achieved in six temporal bones implanted with sodium hyaluronate, compared to 22 patients implanted without sodium hyaluronate. Preliminary biosafety studies measuring hearing thresholds of six cats 4 months after implantation with dummy electrodes did not show evidence of ototoxicity caused by sodium hyaluronate. Until the biosafety studies are complete, we cannot recommend sodium hyaluronate for routine use, but the results so far are promising.

Animals↗
PubMed1995

Improved electrotactile speech processor: Tickle Talker.

The Tickle Talker, an eight-channel electrotactile speech processor, has been developed from continuing research at the University of Melbourne. The development of the device has focused on production of reliable speech-processing hardware, design of cosmetically and ergonometrically acceptable electrode transducers, implementation of acute and chronic biomedical studies demonstrating device safety, design and testing of alternative speech-encoding strategies to provide benefit to speech perception and production, and design and testing of appropriate training methods for optimizing benefits. The Tickle Talker has been shown to provide benefits in supplementing lipreading or aided residual hearing for hearing-impaired adults and children. Improvements in speech processing have resulted in an increase in benefits to speech perception, and open the way for more flexible approaches to encoding speech input. Continuing development of the electrode circuitry has now produced a device that is robust and has an extended battery life. Safety studies have clearly demonstrated that there are no long-term contraindications to device use. The results suggest that the device has a role to play in rehabilitation programs for severely and profoundly hearing-impaired adults and children.

Deafness↗
PubMed1995

Electrophysiologic effects following acute intracochlear direct current stimulation of the guinea pig cochlea.

Auditory brain stem responses to both acoustic (auditory brain stem response [ABR]) and electrical (electrically evoked auditory brain stem response [EABR]) stimuli, as well as the frequency-specific compound action potential (CAP), were recorded before and periodically following continuous intracochlear DC stimulation (2, 7, and 12 microA) for 2 hours in normal-hearing guinea pigs, by means of a banded intracochlear electrode array. Click-evoked ABR, frequency-specific CAP, and the EABR input-output function remained generally unchanged following stimulation at 2 microA DC. However, following stimulation at 7 and 12 microA, a significant decrement of the amplitude of the click-evoked ABR, frequency-specific CAP, and electrophonic component of the EABR was observed, while there was an increase in the amplitude of the EABR, associated with direct electrical stimulation of the auditory nerve.

Acoustic Stimulation↗
PubMed1995

Cochlear pathology following reimplantation of a multichannel scala tympani electrode array in the macaque.

The histopathologic consequence of removing and reimplanting intracochlear electrode arrays on residual auditory nerve fibers is an important issue when evaluating the safety of cochlear prostheses. The authors have examined this issue by implanting multichannel intracochlear electrodes in macaque monkeys. Macaques were selected because of the similarity of the surgical technique used to insert electrodes into the cochlea compared to that in humans, in particular the ability to insert the arrays into the upper basal turn. Five macaques were bilaterally implanted with the Melbourne/Cochlear banded electrode array. Following a minimum implant period of 5 months, the electrode array on one side of each animal was removed and another immediately implanted. The animals were sacrificed a minimum of 5 months following the reinsertion procedure, and the cochleas prepared for histopathologic analysis. Long-term implantation of the electrode resulted in a relatively mild tissue response within the cochlea. Results also showed that inner and outer hair cell survival, although significantly reduced adjacent to the array, was normal in 8 of the 10 cochleas apicalward. Moreover, the electrode reinsertion procedure did not appear to adversely affect this apical hair cell population. Significant new bone formation was frequently observed in both control and reimplanted cochleas close to the electrode fenestration site and was associated with trauma to the endosteum and/or the introduction of bone chips into the cochlea at the time of surgery. Electrode insertion trauma, involving the osseous spiral lamina or basilar membrane, was more commonly observed in reimplanted cochleas. This damage was usually restricted to the lower basal turn and resulted in a more extensive ganglion cell loss. Finally, in a number of cochleas part of the electrode array was located within the scala media or scala vestibuli. These electrodes did not appear to evoke a more extensive tissue response or result in more extensive neural degeneration compared with electrodes located within the scala tympani. In conclusion, the present study has shown that the reimplantation of a multichannel scala, tympani electrode array can be achieved with minimal damage to the majority of cochlear structures. Increased insertion trauma, resulting in new bone formation and spiral ganglion cell loss, can occur in the lower basal turn in cases where the electrode entry point is difficult to identify due to proliferation of granulation and fibrous tissue.

Animals↗
PubMed1994

Prediction of axillary lymph node status in breast cancer patients by use of prognostic indicators.

BACKGROUND: If axillary lymph node status of breast cancer patients could be accurately predicted from basic clinical information and from characteristics of their primary tumors, then many patients could be spared axillary lymph node dissection. Tumor size alone does not allow the identification of groups with very low or high risk of being axillary node positive. PURPOSE: Our goal was to investigate the possibility of using prognostic indicators to predict axillary node status of patients with primary breast cancer. METHODS: Data from 26,683 patients from the National Breast Cancer Tissue Resource were used in this study. Patients in this dataset were randomly assigned to a training set (patient information used to construct predictive models) or a validation set (patient information used to prospectively evaluate predictive models). The records of a total of 11,964 case patients that had complete prognostic factors and pathologic data were analyzed: 5963 patients in the training set and 6001 patients in the validation set. All of the patients studied had tumors 5 cm or less in size and at least 15 axillary lymph nodes that had been examined. Data used for construction of the predictive models were available for all patients and included tumor size, number of nodes positive, patient age, quantitative estrogen receptor levels, quantitative progesterone receptor (PgR) levels, DNA flow cytometry-derived ploidy, and S-phase fraction. Logistic regression models were used to predict nodal status. RESULTS: Multivariate predictive models were produced that used tumor size, patient age, S phase, and PgR as independent predictors. These models allowed identification of patient risks of being node positive ranging from 6%-79% and as having 10 or more positive nodes ranging from less than 1% to slightly more than 30%. CONCLUSION: Addition of prognostic indicator information to tumor size can refine estimates of whether a patient is likely to be node positive. However, no patient subsets could be identified as having greater than 95% chance of being node negative or node positive. IMPLICATIONS: These predictive models cannot alleviate the necessity of axillary node dissection for staging of breast cancer patients in situations in which nodal status would affect therapeutic decisions. Subsets of patients could be identified who had a less than 5% chance of having 10 or more positive nodes. Thus, some patients could be spared axillary dissection if it was being performed solely to identify patients with this high-risk feature.

Axilla↗
PubMed1994

Activity of DMP 840, a new bis-naphthalimide, on primary human tumor colony-forming units.

BACKGROUND: DMP 840 ((R,R)-2,2'-[1,2-ethanediylbis[imino(1-methyl-2,1-ethanediyl)]]- bis[5-nitro-1H-benz[de]-iso[quinoline-1,3(2H)-dione]dimethane- sulfonate; NSC-D640430) is one in a series of bis-naphthalimides that binds DNA with high affinity and has sequence specificity to multiple G and C bases. It is also a potent inhibitor of RNA synthesis. DMP 840 has been selected for clinical evaluation on the basis of a broad spectrum of activity (including cures) in human tumors in murine models. PURPOSE: We evaluated DMP 840 in a human tumor clonogenic assay to estimate what plasma concentrations may be necessary for clinical cytotoxic activity and to determine what types of tumors potentially might be primary targets for initial phase II studies. METHODS: A soft-agar cloning system assay was used to determine the in vitro effects of DMP 840 against cells from biopsy specimens of colorectal, breast, lung ovarian, renal cell, stomach, and bladder cancers and from other tumor types. A total of 260 human tumor specimens were exposed continuously during the assay to DMP 840; 103 were assessable (20 colonies or more on control plates and 30% or less survival for the positive control). An in vitro response was defined as at least a 50% decrease in tumor colony formation resulting from drug exposure compared with controls. RESULTS: In vitro responses were seen in 10% (one of 10), 54% (55 of 101), 80% (82 of 103), and 89% (82 of 92) of specimens tested at 0.01, 0.1, 1.0, and 10.0 micrograms/mL of DMP 840, respectively. At a concentration of 0.1 microgram/mL, specific activity was seen against melanoma (80%) and against renal cell (80%), ovarian (63%), breast (54%), non-small-cell lung (42%), and colorectal cancers (33%). DMP 840 demonstrated activity in tumor specimens resistant in vitro to methotrexate (88%), doxorubicin (58%), platinum (57%), cyclophosphamide (53%), vinblastine (53%), etoposide (53%), fluorouracil (37%), and paclitaxel (36%). CONCLUSIONS: At in vitro concentrations of 0.1 microgram/mL as a continuous exposure, DMP 840 has activity against a variety of human tumors, including a subgroup resistant in vitro to standard antineoplastic agents. IMPLICATIONS: Further clinical development of DMP 840 is warranted.

Antineoplastic Agents↗
PubMed1994

p53 protein accumulation detected by five different antibodies: relationship to prognosis and heat shock protein 70 in breast cancer.

Nuclear accumulation of p53 protein is associated with a poorer clinical outcome in breast cancer patients. Heat shock protein 70 (hsp70) is a chaperone that binds to mutant p53 and consequently could regulate its accumulation or localization. The aims of this study were to determine if the prognostic significance of p53 accumulation was dependent on the type of antibody used for detection and whether hsp70 was associated with this accumulation. Node-negative breast tumors (n = 169) were examined by immunohistochemistry for nuclear p53, cytoplasmic or nuclear hsp70, and for p53 gene alteration by single-strand conformation polymorphism analysis. Frozen sections of pulverized breast tumors were stained with five p53 antibodies (240, 1801, 421, BP53-12, and CM1), a cocktail of both 240 and 1801, and the hsp70 antibody C92. Protein level was expressed as the sum of a proportion and intensity score (total 0, 2-8) with > or = 2 defined as positive staining. The cocktail 240/1801 gave the highest rate of positive staining (45%), followed by BP53-12 (35%), 1801 (27%), 240 (25%), CM1 (24%), and 421 (18%), with a high correlation between antibodies. Positive staining with each individual antibody or the cocktail was significantly associated with estrogen receptor and progesterone receptor negativity, age < 50, and high S-phase fraction. Only staining detected by the 240/1801 cocktail was associated with significantly worse overall survival; 85 versus 70% at 5 years for p53-negative compared to p53-positive tumors, respectively (P = 0.02). There was no association between nuclear or cytoplasmic hsp70 staining and accumulation of p53. Patients that were p53-negative/cytoplasmic hsp70-positive had a better overall survival than those that were p53-negative/cytoplasmic hsp70-negative. No other combination of p53 and hsp70 status could further define subsets of patients with a significantly different prognosis compared to p53 status alone. Tumors without a detectable p53 gene alteration by single-strand conformation polymorphism but with accumulated p53 protein did not have relatively increased levels of hsp70. We conclude that in node-negative breast cancer, the cocktail of two antibodies, 240/1801, resulted in the highest rate of positive staining and was most strongly associated with overall survival compared with either antibody alone or with the other individual antibodies. By immunohistochemistry, nuclear accumulation of p53 was not associated with cytoplasmic or nuclear hsp70 levels.

Adult↗