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Biomedical subjects

G M Clark

Publications and source records attributed to G M Clark.

At least 343 records · Page 19Linked to original sources
PubMed1989

High-dose cisplatin for locally advanced or metastatic head and neck cancer. A phase II pilot study.

High-dose cisplatin (40 mg/m2 every day X5) was administered to 14 patients (11 men, three women) with locally advanced or metastatic head and neck cancer not curable by surgery or refractory to previous chemotherapy and/or radiation therapy. All 14 patients were evaluable for toxicity; one patient was inevaluable for response due to early death. A total of 24 courses of therapy were administered. The dose-limiting toxicity was myelosuppression with 73% of patients experiencing Grade III or IV neutropenia. Grade II or above thrombocytopenia occurred in 30% of the patients. Renal and neurologic toxicity was minimal. Two patients experienced laryngeal edema from vigorous hydration with one of them requiring a tracheostomy for respiratory compromise. Partial responses were seen in six patients (46%). Two of the six patients had received previous treatment with standard dose cisplatin. Two patients achieved long-term responses (54+, 44+ months, respectively). Both of these patients were previously untreated, inoperable (T4N3M0, T3N1M0), and subsequently received radiation therapy after two cycles of chemotherapy. Median duration of response in the remaining responders was 3 months (range, 3-10 months). High-dose cisplatin may benefit selected patients with inoperable, advanced head and neck tumors. However, further randomized trials need to be conducted before firm conclusions can be established.

Adult↗
PubMed1989

Evaluation of factors associated with stability of anticoagulation therapy.

Eighty-two patients receiving long-term warfarin therapy provided 199.34 patient-years of data that were evaluated to determine if certain variables could identify those who might be monitored safely at less frequent intervals. Most patient demographics, social habits, medical histories, indications for anticoagulation, and concurrent therapy were not useful in discriminating between patients with stable (n = 67) and unstable (n = 15) anticoagulation. A few trends were noted, but they failed to achieve statistical significance. Patients who never achieved stability (the unstable group) tended to be younger than those who did (p 0.13). Among the stable patients, those with a diagnosis of deep vein thrombosis or pulmonary embolus, or with elevated alanine aminotransferase values, were significantly more likely to require a dosage change. The probability of requiring a dosage change at monthly visits did not correlate with the time required to become stable, but it did correlate inversely with the duration of stable anticoagulation. This probability declined from almost 16% when monitoring frequency was first extended to monthly intervals to less than 8% at 2 months of stable anticoagulation, and tended to decline further with longer periods of stable therapy. Of the 67 patients who became stable, 23 did not require a dosage change during an average of 526 days of follow-up. Among the 44 stable patients who required a dosage change, the mean time to the change was 250 days after becoming stable. Few complications occurred, almost all of them early in therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

The safety and effectiveness of long-term warfarin therapy in an anticoagulation clinic.

Whenever long-term anticoagulation is prescribed, the risks of such therapy must be evaluated accurately. Whether these risks are influenced by the duration of therapy, the indication for therapy, patient demographics and social habits, or the use of an anticoagulation clinic is controversial. This study examined the occurrence rates of major hemorrhage, minor hemorrhage, and thromboembolic events among an inception cohort of 82 patients receiving long term-warfarin therapy in an anticoagulation clinic. During 199.34 patient-years of observation, there were 4 major hemorrhages (0.0201/patient-year), 31 minor hemorrhages (0.1555/patient-year), and 7 thromboembolic events (0.0351/patient-year). Although each type of event tended to occur during the first 6 months of therapy, this trend was not statistically significant. Failure to demonstrate statistically significant influence of any of the evaluated variables may have been due to the unusually low rate of complications, a finding that may reflect the safety of anticoagulant therapy when managed by a specialized clinic.

Adult↗
PubMed1989

A method for the evaluation of dose-toxicity relationships in clinical trials.

This paper considers a proportional hazards model that describes the relationship between time-dependent cumulative dose of drug and development of toxicity. We estimate probabilities of developing toxicity in both the presence and the absence of competing risks and provide variances for the latter case. Mitoxantrone data collected in Southwest Oncology Group studies illustrate the methods.

Adult↗
PubMed1989

Prognostic factors in breast cancer.

There are several independent but interrelated prognostic factors predictive of recurrence and survival in breast cancer. These include axillary nodal status, histopathology, steroid receptors, proliferative rate, ploidy, and oncogene amplification. Axillary nodal status has been the traditional mainstay predictor for recurrence and survival in primary breast cancer. In addition, the presence of the estrogen and progesterone receptors has correlated with longer disease-free interval and overall survival in stage I and II breast cancer. Thymidine-labeling index and percent S-phase as measured by flow cytometry are indices of cell proliferation that correlate with relapse rate in pre- and postmenopausal women with breast cancer. Estrogen and progesterone receptor-negative tumors are more commonly aneuploid, and have higher percent S-phase, factors that predict for recurrence in Stage I breast cancer.

Axilla↗
PubMed1989

Evaluation of an amsacrine analog in a human tumor cloning system.

A human tumor-cloning system was used to compare the antitumor activity of CI-921, a new amsacrine analog with that of its parent compound (amsacrine gluconate). A total of 48 specimens of 9 histologically different types of human malignancy were evaluable for a direct comparison of the cytotoxic activity. Both compounds were tested simultaneously at 10 micrograms/ml final concentration under continuous exposure. The overall activity was similar for both drugs, but the degree of cross-resistance was low. We concluded that in patients, CI-921 might have a different spectrum of antitumor activity from that of its parent compound.

Amsacrine↗
PubMed1989

Prognostic factors for recurrence and survival in axillary node-negative breast cancer.

The question of which node-negative breast cancer patients should be treated with adjuvant systemic therapy is a debatable topic. Our approach in San Antonio is to examine the risk profile for an individual patient and attempt to classify the patient into a good risk group or a high risk group in terms of disease recurrence. Features such as small tumor size (less than 2 cm), diploid tumors with low proliferative rate, and nuclear grade I, all indicate a good prognosis with a disease-free survival of approx. 90% at 5 yr. Examination of the cost vs benefits in this category of patients suggest that routine treatment with systemic adjuvant therapy is not appropriate.

Biomarkers, Tumor↗
PubMed1989

Thyroid dose distribution in dental radiography.

The anatomic position and proven radiosensitivity of the thyroid gland make it an organ of concern in dental radiography. A calibrated thermoluminescent dosimetry system was used to investigate the absorbed dose (microGy) to the thyroid gland resultant from a minimum irradiated volume, intraoral full-mouth radiography technique with the use of rectangular collimation with a lead-backed image receptor, and conventional panoramic radiography performed with front and rear lead aprons. Use of the minimum irradiated volume technique resulted in a significantly decreased absorbed dose over the entire thyroid region ranging from 100% to 350% (p less than 0.05). Because this intraoral technique results in radiographs with greater image quality and also exposes the thyroid gland to less radiation than the panoramic, this technique may be an alternative to the panoramic procedure.

Equipment Design↗
PubMed1989

Phase I trial of echinomycin (NSC 526417), a bifunctional intercalating agent, administered by 24-hour continuous infusion.

Echinomycin was administered to 43 patients with advanced cancer in escalating doses ranging from 60 to 2128 mcg/m2. The dose-limiting toxicity of echinomycin administered as a 24-h continuous infusion every 28 days was nausea and vomiting beginning at the end of the 24 h infusion and lasting from 3 to 8 days. Other toxicities included sporadic thrombocytopenia and biochemical evidence of liver dysfunction characterized by elevations in SGOT. Peripheral vein phlebitis was noted in 100% of patients, and watery diarrhea of 24-48-h duration was noted in 7% of patients. The maximally tolerated dose of echinomycin was 2128 mcg/m2. The recommended dose for phase II trials utilizing the 24-h continuous infusion schedule is 1600 mcg/m2 repeated every 28 days with pretreatment antiemetics.

Adult↗
PubMed1989

The relationships of SHBG with current and previous use of oral contraceptives and oestrogen replacement therapy.

Sex hormone binding globulin (SHBG) concentration was measured in serum samples from 2077 premenopausal and 901 naturally postmenopausal women who had no history of disease or of recent drug use likely to affect SHBG. Current users of oral contraceptives (OCs) and of oestrogen replacement therapy had higher mean SHBG values than non-current users. Both premenopausal and postmenopausal women who had previously used OCs had a lower mean SHBG concentration than never users of OCs. Previous use of oestrogen replacement therapy was not related to SHBG.

Adult↗
PubMed1989

A new in vitro screening system for anticancer drugs for the treatment of non-small cell lung cancer.

We have evaluated a semiautomated radiometric assay (BACTEC 460 system) for screening of activity of anticancer drugs against human non-small cell lung cancer cell lines. Cells from seven cell lines were exposed to standard antineoplastic agents at four different concentrations using a 1-h incubation. Alpha 2-interferon was tested using a continuous incubation. In vitro drug activity was analyzed as a function of the clinically achievable serum concentration. Our results indicate that two cell lines (CALU-3, SK-MES-1) exhibit in vitro drug sensitivity patterns closest to those observed in clinical studies. These two cell lines might therefore be most useful for screening new anticancer compounds for activity against non-small cell lung cancer. The radiometric assay is a semiautomated system which has advantages over other, more time-consuming screening systems.

Antineoplastic Agents↗
PubMed1989

Technique-dependent decrease in thyroid absorbed dose for dental radiography.

A LiF thermoluminescent dosimetry (TLD) system, calibrated in the tissue of interest with the beam used for experimentation, was employed to investigate dosages (muGy) to the thyroid region of an anthropomorphic phantom resultant from two dental complete-mouth radiographic procedures. Both techniques were compared in terms of dosages associated with combinations of lead apron and thyroid collar shielding while using a 70-kVp or 90-kVp x-ray beam for a 20-film complete-mouth series. Lead shielding significantly decreased the dose to the thyroid using both techniques (p less than 0.05). The use of the 90-kVp beam resulted in a significant reduction in the thyroid absorbed dose when using the bisecting angle technique (p less than 0.05) but caused a significant increase in the thyroid absorbed dose when the paralleling technique was used (p less than 0.05). The implementation of higher kilovoltage techniques in dental offices must therefore be dependent on the radiographic technique employed.

Humans↗
PubMed1989

Use of a simulation model in occupational dose assessment at a high-level radioactive waste repository.

Occupational radiation dose assessment at a nuclear facility can benefit from a systems approach that recognizes the complex dynamics of the facility. A simulation model can be a useful tool for accomplishing this goal. This technique can quantify the uncertainty in estimates of occupational dose equivalent and illustrate the effects of system interactions. A simulation model of operations at a high-level radioactive waste repository together with a radiological dose assessment model were used to illustrate this technique. Annual individual and collective occupational dose equivalents were estimated in the truck cask receiving and handling stations at a repository. The uncertainty of these estimates is shown through the use of complementary cumulative distribution functions. The effects of changing parameters in cask handling operations are examined.

Computer Simulation↗
PubMed1989

Speech perception studies using a multichannel electrotactile speech processor, residual hearing, and lipreading.

Three studies are reported on the speech perception of normally hearing and hearing-impaired adults using combinations of visual, auditory, and tactile input. In study 1, mean scores for four normally hearing subjects showed that addition of tactile information, provided through the multichannel electrotactile speech processor, to either audition alone (300-Hz low-pass-filtered speech) or lipreading plus audition resulted in significant improvements in phoneme and word discrimination scores. Information transmission analyses demonstrated the effectiveness of the tactile aid in providing cues to duration, F1 and F2 features for vowels, and manner of articulation features for consonants, especially features requiring detection and discrimination of high-frequency information. In study 2, six different cutoff frequencies were used for a low-pass-filtered auditory signal. Mean scores for vowel and consonant identification were significantly higher with the addition of tactile input to audition alone at each cutoff frequency up to 1500 Hz. The mean speechtracking rate was also significantly increased by the additional tactile input up to 1500 Hz. Study 3 examined speech discrimination of three hearing-impaired adults. Additional information available through the tactile aid was shown to improve speech discrimination scores; however, the degree of increase was inversely related to the level of residual hearing. Results indicate that the electrotactile aid may be useful for patients with little residual hearing and for the severely to profoundly hearing impaired, who could benefit from the high-frequency information presented through the tactile modality, but unavailable through hearing aids.

Adult↗
PubMed1989

Results for two children using a multiple-electrode intracochlear implant.

Assessments in speech perception, speech production, and language skills were conducted on two children, 5 and 10 years old at the time of surgery, using the Nucleus multiple-electrode cochlear implant. Data were collected pre- and post-operatively to measure changes in performance over time. For closed-set speech perception tests in the audition alone condition, post-operative performance was generally better than pre-operative performance and performance improved post-operatively for both patients. In closed-set vowel and consonant identification and open-set sentence perception for the older patient, post-operative improvements from the vision alone to the auditory-visual condition were recorded and performance improved post-operatively in both conditions. In all measures of speech production for both patients, post-operative scores were higher than pre-operative scores and performance improved post-operatively. In language skills, post-operative scores were higher than pre-operative scores and scores improved post-operatively in all measures for both patients.

Child↗
PubMed1989

Forward masking patterns produced by intracochlear electrical stimulation of one and two electrode pairs in the human cochlea.

Three psychophysical forward masking studies were conducted on a multichannel cochlear implant patient. The first study investigated the masking pattern produced by a bipolar electrode pair at different stimulus currents. It was found that the masking pattern for a single-masker bipolar electrode pair had a maximum located at an electrode position where the masker and probe coincided. The spread of the masking pattern was not symmetrical about the maximum. The amount of masking decreased very rapidly toward the apical direction and less rapidly toward the basal direction from the position of the maximum. As the stimulus current increased, the amount of masking at the maximum increased and the masking pattern broadened toward the base. The second study investigated the masking pattern produced by the activation of single bipolar electrode pairs with different spatial extents. The spatial extent of a bipolar electrode pair is defined as the distance between the apical and basal electrode members of the bipolar pair. With a small spatial extent (1.5 mm), the more basal electrode pairs (higher threshold and smaller dynamic range) produced broader masking patterns than the more apical electrode pairs (lower threshold and wider dynamic range), suggesting that there was more current spread at the basal region. With a larger spatial extent (4.5 mm), an additional secondary masking maximum was observed in the vicinity of the apical electrode member of the masker; this was observed only when the apical electrode member lay within the low-threshold apical region. The third study investigated the masking patterns produced by two loudness balanced bipolar masker electrode pairs activated within a stimulus period (inverse of the pulse repetition rate). The biphasic current pulses delivered to the two electrode pairs were nonoverlapping in time. It was found that, at any probe electrode position, the amount of masking produced by the two combined bipolar electrode pairs approximately followed the greater of the two maskings produced respectively by the two individual bipolar masker electrode pairs.

Cochlea↗