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Biomedical subjects

D J Sutherland

Publications and source records attributed to D J Sutherland.

At least 37 records · Page 2Linked to original sources

The use of endocrine therapy.

Endocrine therapy is still a mainstay in the treatment of metastatic breast cancer. It has been observed that about one third of women with metastatic breast cancer will respond to endocrine therapy. This response rate is surprisingly consistent for a wide variety of endocrine approaches, with a few exceptions, such as the use of corticosteroids, androgens, or danazol for which the response rate appears lower. Endocrine therapy is, in general, considerably less toxic than single or combination chemotherapy, but toxicities within the endocrine therapies may vary considerably. Thus, the choice and optimal sequencing of endocrine maneuvers relate largely to minimizing toxicity and optimizing total duration of benefit. A number of newer endocrine approaches including the antiestrogens and aminoglutethimide have recently provided a variety of less toxic choices. Even more recently, compounds such as the LHRH agonists and antiandrogens are being tested, although their use remains experimental. Combinations of two or more endocrine therapies or of chemotherapy and endocrine therapy are currently, also a subject of considerable interest. No studies to date, however, have shown a clear advantage to concurrent chemotherapy endocrine combinations or to the use of two or more concurrent hormonal maneuvers, with the possible exception of the combination of prednisolone with tamoxifen or with oophorectomy, which has improved overall survival in two trials.

Adrenalectomy↗

Gynecologic-obstetric changes after loss of massive excess weight following bariatric surgery.

A clinical study was undertaken to assess gynecologic-obstetric changes in morbidly obese women who lost greater than or equal to 50% of their excess weight with bariatric surgery. The 138 females (109 of reproductive age), age 35 +/- 9 SD yr, weighed 124 +/- 23 kg before surgery and 79 +/- 13 kg after weight loss had stabilized. Menstrual irregularities were present in 40.4% of premenopausal patients preoperatively; after massive weight loss, cycles were abnormal in 4.6% (p less than 0.001). Infertility problems were present preoperatively in 29.3% Of these, nine tried to conceive after weight loss and were successful. During past pregnancies, medical complications were frequent (hypertension 26.7%, pre-eclampsia 12.8%, diabetes 7.0%, and deep vein thrombosis 7.0%). After weight-loss stabilization, these obstetric complications did not occur. Incidence of urinary stress incontinence decreased from 61.2% to 11.6% (p less than 0.001). Gynecologic-obstetric changes tended to normalize after loss of massive body weight.

Adolescent↗

Susceptibility status of Aedes albopictus to three topically applied adulticides.

The baseline susceptibility of Aedes albopictus (Sabah strain) to malathion was determined. Both laboratory-colonized and field-collected Ae. albopictus at Harris County, TX are resistant to malathion but susceptible to Scourge. The acute toxicity of bendiocarb to Ae. albopictus is confounded by its rapid knockdown and delayed recovery syndrome of poisoning.

Aedes↗

Role and mechanism of action of tamoxifen in premenopausal women with metastatic breast carcinoma.

Tamoxifen was evaluated as initial hormone therapy for metastatic breast cancer in 85 premenopausal patients. Tamoxifen responders continued on tamoxifen, while tamoxifen failures and initial responders who later progressed were to receive ovarian ablation next. Of 74 evaluable patients, 5 had complete responses (CR) and 15 had partial responses (PR) while 12 remained stable (ST), giving response rates of 27% (CR + PR) or 43% (CR + PR + ST). Of the 23 patients who initially responded (CR + PR + ST) to tamoxifen but then progressed and received ovarian ablation alone, 15 are assessable. Nine (60%) responded (CR + PR + ST) to ovarian ablation. Sixteen patients who failed tamoxifen had ovarian ablation alone, and of 14 assessable patients 2 had ST while 12 progressed. Thus response to tamoxifen strongly predicted response to ovarian ablation (P = 0.021). Serial follicle stimulating hormone, prolactin, and estradiol levels suggested that tamoxifen does not act by induction of a "medical ovariectomy" or by alteration of prolactin levels in premenopausal patients.

Breast Neoplasms↗

Inter-laboratory quality control of estrogen and progesterone receptor assays in breast cancer tissue using lyophilised cytosols.

In 1981 a quality control (QC) program for estrogen and progesterone receptor assays was organized among six laboratories in Ontario, Canada. Twenty-three vials of lyophilised cytosol prepared from human breast tumor tissues were analysed by each laboratory over a two-year period. Samples of each batch of QC material were analysed at least twice: either in the same batch or on separate occasions. The present study demonstrates the stability of the QC material, defines the relative accuracy of the receptor assays, and provides estimates of within-batch and between-batch precision of the receptor assays.

Breast Neoplasms↗

Exercise electrocardiographic mapping in normal subjects.

To investigate the spectrum of change in multiple-lead exercise electrocardiograms, 120-lead body surface potential maps (BSPM) in normal adult subjects during upright, graded, submaximal exercise testing were recorded. Results showed that in the normal group, exercise was associated with substantial electrocardiographic changes on the body surface, many of which persisted during early recovery. The QRS waveform was minimally altered during exercise. Despite, however, no change in QRS duration, there was significant reduction in QRS potential range with consequent reduction QRS integral value. The ST waveforms changed markedly with exercise, showing abbreviated duration and increased slope. This was reflected by significantly increased ST potential range from rest to immediate cessation of exercise, which returned towards resting value during recovery. The effect of the altered ST-segment waveform was also reflected in torso potential distributions at two time instants during the ST-segment. When a spatially-fixed position on the ST-T waveform was evaluated (ST-segment offset), exercise resulted in small potential changes, especially over the torso area occupied by the standard V1 to V6 chest leads. However, when a temporally-fixed point (80 ms after QRS offset) was evaluated, there were large increases in potential over the precordium with exercise. Isointegral ST-segment maps, which reflect both spatial and temporal ST properties, showed that exercise was associated with substantial decreases in values over the precordium and inferior torso, and although diminished, they tended to persist through five minutes of recovery. Thus, electrocardiographic repolarization parameters are particularly affected by physiological exercise and, although the underlying causes of these changes remain undefined, they should be taken into account when evaluating the population at risk.

Adult↗

The effect of caffeine on cardiac rate, rhythm, and ventricular repolarization. Analysis of 18 normal subjects and 18 patients with primary ventricular dysrhythmia.

To determine clinical electrophysiologic effects of a moderate dose of caffeine, we compared prevailing cardiac rhythm and rate, the prevalence and frequency of ventricular dysrhythmia, and Q-T intervals in two populations over an initial 24-hour caffeine-free period and a subsequent 24-hour period in which caffeine was ingested in a dosage of 1 mg/kg of body weight at intervals of one half-life during waking hours. Group 1 was composed of 18 clinically normal subjects; group 2 was 18 subjects with frequent ventricular ectopic beats (VEBs) and no (n = 16) or minor (n = 2) cardiac disease. Sinus rhythm was the prevailing rhythm in all subjects at all times. For group 1, the mean sinus rate during the caffeine-free period was 77 +/- 10 beats per minute, compared to 73 +/- 9 beats per minute during the period of caffeine ingestion (not significant). Similarly, for group 2, the average sinus rate during the caffeine-free period was 76 +/- 11 beats per minute, not significantly different from the average sinus rate during the test period, 76 +/- 10 beats per minute. During abstention from caffeine, four of 18 subjects in group 1 had infrequent (less than 1/hr) VEBs, compared to nine of 18 during caffeine ingestion (not significant). In group 2, some 16 of the 18 subjects had VEBs during the caffeine-free period, with the frequencies varying from less than one VEB per hour to 1,449 VEBs per hour. During the test period, 14 of the 18 subjects in group 2 increased their VEB frequency, and the group's mean frequency rose from 207 +/- 350 VEBs per hour (control period) to 307 +/- 414 VEBs per hour (test period) (p less than 0.01). The Q-T interval in group 1, measured as the corrected Q-T interval (Q-Tc), averaged 0.430 +/- 0.027 during the caffeine-free period, not significantly different from the test period (0.425 +/- 0.019). The comparable Q-Tc values for group 2 were 0.424 +/- 0.018 during the caffeine-free period and 0.433 +/- 0.025 for the period of caffeine ingestion (not significant).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Plasminogen activator activity in human breast cancer cytosols.

Plasminogen activators are an enzyme complex which first appears in the trophoblast and may contribute to the invasive and metastatic process in neoplastic growth. In this study, 102 cytosols from human breast cancer biopsies were analyzed for PAA (with the chromogenic tripeptide S2251 KABI), steroid receptors (ER and PR), age, nodal and menopausal status. The data were submitted to log (X + 1) transformation and the raw and transformed data were analyzed for distribution. Because of the largely non-normal distribution of the data, Spearman's rank order correlation coefficients were generated to test for relationships between these differentiation markers and the clinical data. Nodal and menstrual status groups were compared for PAA and receptor levels using the Wilcoxon rank sum test. We found significant positive correlations between net PAA and ER (p = 0.0001), net PAA and PR (p = 0.0001), and net PAA and age (p less than 0.05). PAA levels for nodal status groups were found to be significantly different (negative at p less than 0.05). Nodal metastases predict poor prognosis while higher receptor levels indicate a better prognosis. As PAA levels correlate with the above biologic properties of breast tumors, they may provide additional prognostic information, especially in cases in whom auxiliary node status is unknown.

Breast Neoplasms↗

Distribution of heavy metals and radionuclides in sediments, water, and fish in an area of Great Bear Lake contaminated with mine wastes.

The concentrations of heavy metals and radionuclides in the sediments and water of Great Bear Lake were determined during 1978 near an operating silver mine and an abandoned uranium mine. Additional information on the level of mercury in fish tissues were also collected. The mines, situated on the same site, deposited tailings and other waste material directly into the lake. The concentrations of mercury, lead, manganese, and nickel in the sediments were highest near the tailings deposit and decreased significantly as the distance from the mine increased. Although there were also significant positive correlations between these metals and the organic content of the sediments, water depth and slope of the bottom had no impact on metal distribution. Since the concentrations of arsenic, cobalt, copper, 226radium, 210lead and 230thorium varied inconsistently throughout the study area, the distribution of these substances could not be related to any of the environmental factors that were measured. There were, however, significant negative correlations between the concentrations of 232thorium and 228thorium and distance from the mine and organic content of the sediments. Heavy metal and radionuclide levels in water were generally below detectable limits, reflecting the strong chemical bonding characteristics of the sediments. The low concentrations of mercury in the tissues of lake trout Salvelinus namaycush were probably related to low uptake rates and the ability of this species to move into uncontaminated areas of the lake.

Animals↗

Body weight and prognosis in breast cancer.

We have examined the relationship between risk factors for breast cancer incidence and the subsequent prognosis of breast cancer among patients in a randomized controlled trial of adjuvant ovarian ablation. Body weight was the only risk factor found to be associated with statistically significant differences in survival. This finding could not be explained by a disproportionate number of anatomically more advanced tumors in the heavier women. In premenopausal women aged 45 years or more, the only group to benefit from adjuvant ovarian ablation, there was an interaction of treatment and weight, suggesting that weight exerts its influence on prognosis by a hormonal mechanism. The prognostic effect of weight was generally most marked in patients with tumors whose prognostic characteristics were favorable, and in these patients weight loss as an adjuvant treatment may reduce the frequency of disease recurrence.

Adult↗

Chemotherapy for adenocystic carcinoma.

Seventeen patients with adenocystic carcinoma have received 34 adequate trials of chemotherapy at Princess Margaret Hospital since 1969. There have been five objective responses to chemotherapy in 4 cases, lasting from five to 24 months, and 3 other patients have had stabilized disease for a period of five to seven months. Responding and stabilized patients all had symptomatic improvement. Most responses were to 5-fluorouracil, the preferred drug for initial treatment of metastatic disease or locoregional disease that cannot be controlled by means of surgery or radiation therapy.

Alkylating Agents↗

Plasminogen-activating activity: association with steroid binding by cytosols of human breast cancers.

Plasminogen-activating activity (PAA) was determined on cytosols prepared from human breast cancers. Coincident assays of steroid-binding proteins were obtained for 119 patients. Significant positive correlations were found between PAA and binding of: 1) estrogen (P less than 0.01), 2) progestin (P less than 0.001), and 3) triamcinolone (P = 0.01). Stepwise regression analysis indicated that variations in the levels of progestin binding accounted for 17% (P less than 0.01) and variations in the levels of triamcinolone binding for 3% (P = 0.05) of the variation observed in PAA. Use of the median value of each assay to discriminate positive from negative values accentuated the positive correlation between PAA and binding of 1) estrogen (P = 3.9 X 10(-5), 2) progestin (P = 1.9 X 10(-4), and 3) triamcinolone (P = 6.1 X 10(-5). Preliminary results suggested that values of PAA equal to or greater than the median correlated positively with response to treatment by hormone manipulation (P = 0.0549). Possible significance of these observations was discussed.

Breast Neoplasms↗

Carcinoembryonic antigen in breast cancer.

Carcinoembryonic antigen (CEA) levels were determined in 742 postoperative patients with breast cancer. Within this group the percentage of elevated (greater than or equal to 4.0 ng/ml) assays increased with UICC clinical stage and was 14.8% (12/81), 23.7% (27/114), 73.1% (190/260) and 20.0% (49/245) for stages I, II, III, IV and X (unstagable due to insufficient data) patients. We have now followed the above 482 stages I, II, III and X patients in whom CEA was performed less than or equal to 3 months after initial surgery at a time when there was no evidence of residual disease, for an average interval of 255 days from date of diagnosis. At present 16.2% (17/105) of patients with elevated CEA values compared to only 4.8% (18/377) of patients with normal values have developed recurrent disease (p less than .0005). There is an association of elevation of CEA postoperatively with different clinical stages of breast cancer. Elevated CEA levels postoperatively are associated with an increased risk of development of recurrent disease in breast cancer patients.

Breast Neoplasms↗