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Biomedical subjects

A M Walker

Publications and source records attributed to A M Walker.

At least 307 records · Page 17Linked to original sources

Oral contraceptives and breast cancer.

The incidence of breast cancer among users and non-users of oral contraceptives (OCs) was determined at Group Health Cooperative of Puget Sound, Seattle, Washington, a health care organization which maintains computer files of diagnoses and outpatient drug use. In women 45 years of age or younger, the incidence was nearly identical in users and non-users. In premenopausal women over 45 years of age, there was a positive association between current OC use and breast cancer, the risk ratio estimates and 90% confidence intervals being 4.0 (1.8-9.0) in women 46-50 years of age and 15.5 (5.2-46) in women 51-55 years of age.

Adult↗

Replacement estrogens and breast cancer.

The relation between replacement estrogens and breast cancer in menopausal women (age 45-64 years) was evaluated in the Group Health Cooperative of Puget Sound, Washington State, a prepaid health care organization with fully computerized information on outpatient drug use and hospital diagnoses. Little association between current estrogen use and breast cancer was noted in women with a previous hysterectomy (relative risk (RR) = 1.1; 90% confidence interval (Cl), 0.7-1.8). In women with a natural menopause there was a positive association between current estrogen use and breast cancer (RR = 3.4; 90% Cl, 2.1-5.6). This association was strong in naturally menopausal women aged 45-54 years (RR = 10.2) and weaker in the older age group (RR = 1.9).

Breast Neoplasms↗

Multiple sclerosis in the Orkney and Shetland Islands. II: The search for an exogenous aetiology.

In Orkney and Shetland, a survey of lifetime events was undertaken in multiple sclerosis patients and two control groups to define shared exposure to an exogenous agent or environmental insult. Analyses of demographic factors, diet, social class and occupation, housing and environment, animal exposure, schooling, travel, infectious disease, and medical history disclosed a remarkable similarity in responses between patients and controls for a majority of questions. However, differences were noted for sanitation, place of residence at onset, and animal exposure. The data give additional support for an exogenous aetiology of multiple sclerosis.

Animal Population Groups↗

Effect of alpha-adrenergic agonist and antagonist infusion on the umbilical and uterine circulations of pregnant sheep.

The effects of the alpha-adrenergic agonists, norepinephrine and methoxamine, and the alpha-antagonist, phenoxybenzamine, on umbilical and uterine blood flows, fetal and maternal heart rates, arterial and venous pressures were examined in near-term chronic sheep preparations. Norepinephrine injection or methoxamine infusion to either fetus or ewe resulted n a respective unilateral fetal or maternal pressur response associated with bradycardial. Uterine blood flow decreased significantly with alpha-agonist administration to either fetus or ewe. Umbilical blood flow did not change with either, but an increase in calculated umbilicalo vascular resistance did occur after fetal administrations of the alpha-agonist. Thus, both the uterine and umbilical vascular beds are responsive to alpha-agonism, but maternal uteroplacental perfusion appears to be more sensitive. alpha-Blockade in either fetus or mother produced no significant changes in umbilical or uterine blood flows or fetal or maternal perfusion pressure suggesting that basal alpha-adrenergic tone is unnecessary for normal maintenance of either fetal or maternal uteroplacental circulation.

Adrenergic alpha-Agonists↗

Preferential release of newly synthesized prolactin granules is the result of functional heterogeneity among mammotrophs.

Pituitary cells maintained in monolayer culture for 48 h were used for double isotope labeling to study the release of newly synthesized vs. old PRL. The intracellular pathway taken by newly synthesized PRL was studied by autoradiography. For double labeling the cells were first incubated in a 14C-labeled amino acid (4 h) and then in a 3H-labeled amino acid (1 h), each followed by a 1-h chase. Total PRL (RIA) and radiolabeled PRL (immunoprecipitation) were determined in both cells and media. Thre rate of release of PRL (RIA) was stable throughout the experimental period. In unstimulated cells the ratio of 3H- to 14C-labeled PRL in the medium at the end of a 1-h incubation following the second chase was twice that in the cells at the beginning of this incubation, indicating that newly synthesized [3H]PRL was preferentially released. Stimulation with TRH resulted in increased release of older [14C]PRL. The earliest that radiolabeled (14C or 3H) PRL could be detected in the medium was 15--30 min after exposure of the cells to isotope. For autoradiography, cells were given a 5-min pulse of [3H]leucine, followed by chase periods of 30--180 min. Grain counts indicated that mammotrophs maintained in culture for 48 h transported and packaged PRL with the same time course as those preparations studied previously. Analysis of the distribution of total grains per cell in mammotrophs revealed the presence of several functional subpopulations with different numbers of total grains per cell, indicating that some cells were manufacturing and secreting PRL at a very fast rate. It is concluded that 1) preferential release of newly synthesized PRL is due to preferential discharge of newly synthesized granules, since release occurs at a time when labeled hormone is already in the granules; 2) there is no evidence that the established secretory pathway is bypassed, since transport, concentration, and granule formation occur; and 3) preferential release of newly synthesized PRL is the result of functional heterogeneity within the mammotroph population. Functional heterogeneity is illustrated by major differences in both synthetic rates and TRH responsiveness.

Animals↗

The epidemic of endometrial cancer: a commentary.

Vital statistics show that a rise in incidence of endometrial cancer began in the mid-1960s on the West Coast of the United States. This rise was continuous and reached a peak in 1975. Elsewhere, incidence rates for endometrial cancer rose during the 1970s. It now seems evident that much of the rise in all areas of the country was due to replacement estrogen treatment. We estimated from data obtained from the Commission on Professional and Hospital Activities-Professional Activity Study of Ann Arbor, Michigan, that over 15,000 cases of endometrial cancer were caused by replacement estrogens during the five-year period 1971--1975 alone. This represents one of the largest epidemics of serious iatrogenic disease that has ever occurred in this country. With the substantial fall in estrogen sales starting in January 1976, there has been an associated decline in the incidence rates of endometrial cancer nationwide.

Aged↗

Assessment of the response of tumours to radiation: clinical and experimental studies.

There is an important and active research programme at the laboratory and clinical level to develop indicators of the ultimate local response of tumours to radiation. In order to be of great value clinically indicators should yield a high true positivity and a low false positivity so that revisions of therapeutic strategy will be made only when there is a real need for such a change. The available data in the literature from the clinical studies, when analysed in terms of the true and false positive rates, indicate that the extent of regression at the completion of external beam therapy is not a useful prognostic indicator. This pertains to populations of tumour of a specific histopathological type, tumour size and anatomic site. Studies of laboratory animal tumour models have shown that regression patterns may be useful prognostic indicators for a tumour which is characterized by moderate immunogenicity and where there is close correlation between complete regression and permanent control. In contrast for tumours which are weakly or nonimmunogenic and which regress completely even at low tumour control probabilities, the pattern of regression has not been demonstrated to be of prognostic value.

Animals↗

Periodic breathing in siblings of sudden infant death syndrome victims.

To determine the incidence of periodic breathing (PB) episodes during sleep, 48 subsequent sudden infant death syndrome siblings and 48 control infants, matched by sex, gestational age, and chronologic age, were studied by home pneumogram technique. The sudden infant death syndrome siblings had a statistically significant increase in the percent of sleep time spent in PB, in the number of episodes/100 minutes of PB, in the longest episode PB, and in the average duration of all episodes of PB. We conclude that PB is present in a higher amount in sudden infant death syndrome siblings as compared to control infants.

Cheyne-Stokes Respiration↗

Declining rates of endometrial cancer.

In the United States edometrial cancer among women in their fifties has been declining since 1975 after having risen throughout the earlier part of the decade. Rates for older women have continued to rise steadily, suggesting that the early postmenopausal population may have determinants of endometrial cancer not shared by other age groups.

Adult↗

Drug-related superinfection in hospitalized patients.

In a series of 14,077 hospitalized medical patients receiving antibiotics, superinfection developed in 95 (0.7%) during drug therapy. The majority were yeast and fungal infections, and serious infections occurred with a frequency of less than one per 1,000 patients treated. Concurrent immunosuppression and impaired renal function increased the risk of new infections.

Adult↗

Replacement estrogens and endometrial cancer.

We examined the incidence of endometrial cancer in a large prepaid group practice in the Seattle area. From July, 1975, to July, 1977, there was a sharp downward trend in the incidence of endometrial cancer that paralleled a substantial reduction in prescriptions for replacement estrogens. Incidence rates were estimated for estrogen users and nonusers among women 50 to 64 years of age with intact uteri; current long-term users had an annual risk for endometrial cancer between 1 and 3 per cent, whereas nonusers had a risk less than 1/10th as great. These incidence rates remained fairly constant over time among users and nonusers; the drop in overall incidence soon after estrogen use declined suggests that the increased risk associated with estrogens falls quickly after discontinuation. The reduction in incidence of endometrial cancer in this group practice was part of a general decline in the United States after 1975.

Estrogens↗

Temporal and regional variation in hysterectomy rates in the United States, 1970--1975.

Regional hysterectomy rates in the United States for 1970 and 1975 have been estimated from a one per cent sample of hospital discharges. All rates have been corrected for the number of women truly at risk, that is, with uteri intact, and regional and age-specific estimates of uterine prevalence in 1975 are provided. The rates rose by one-third in 1970-1975, with the increase taking place nearly uniformly over all ages below 65 years. Rates were greatest for 40--44-year-old women, but in 1970 there was a secondary peak for women between the ages of 65 and 69 years. That peak disappeared with rising rates for younger women in 1975. For women under age 35 years, the hysterectomy rate in the South was three times higher than that in the Northeast.

Adult↗

Cancer of the corpus uteri: increasing incidence in the United States, 1970--1975.

Incidence rates of cancer of the corpus uteri have been estimated from a one per cent sample of hospital discharges in the United States for the years 1970--1975. Among postmenopausal women, rates rose sharply in 1970--1975, while for younger women there was little net change. There were substantial regional variations in incidence, which were largest between the ages of 65 and 69 years. All rates have been corrected for the numbers of women in each region and age group with uteri intact.

Adult↗

Age-dependent pattern of autonomic heart rate control during hypoxia in fetal and newborn lambs.

Autonomic nervous control of heart rate (HR) during hypoxia was studied longitudinally using 9 chronically catheterized fetal lambs (109 day to term) and 10 newborn lambs (2--28 days old). Changes in heart rate (deltaHR) during hypoxia were age-dependent. Before 120 days of gestation deltaHR was insignificant, but between 120 days to term bradycardia occurred. The newborn response was marked tachycardia. Autonomic influences on HR were quantified using atropine and propranolol blockade. In fetal lambs, antagonistic increases in parasympathetic and sympathetic outflows were evident during hypoxia. In hypoxic lambs 120 days to term, net bradycardia reflected predominant parasympathetic cardio-deceleration; before 120 days of gestation both the parasympathetic and sympathetic outflows increased, but no net deltaHR occurred. In hypoxic newborn lambs, sympathetic and parasympathetic changes contributed synergistically to the net tachycardia. Thus the pattern of autonomic control of HR during hypoxia differs in fetal and newborn lambs. Changes in sympathetic and parasympathetic influences are antagonistic in the fetus, but synergistic in the newborn.

Age Factors↗