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Biomedical subjects

W R Miller

Publications and source records attributed to W R Miller.

At least 271 records · Page 15Linked to original sources
PubMed1983

Effects of drugs associated with hyperprolactinemia on plasma steroids and on steroid receptors and metabolism in human breast cancer.

Certain commonly taken pharmaceutical preparations induce increased levels of plasma prolactin. The effects of these drugs on (a) tumor steroid receptors and metabolism, and (b) plasma hormones and hormone binding proteins have been studied in postmenopausal women with breast cancer. Two groups have been compared, 18 patients on drug treatment for at least 2 months and 15 subjects with no history of drug ingestion. Patients taking medication had significantly higher levels of plasma prolactin compared with control women. No significant difference was observed between the groups with regard to the plasma concentrations of dehydroepiandrosterone (DHA) and its sulphate (DHS), testosterone, estrone, estradiol-17 beta, sex hormone binding globulin (SHBG), and albumin. Similarly, no difference was observed between these two groups with regard to estrogen receptor (ER), progestogen receptor (PR), or androgen receptor (AR) levels in the tumors nor their ability to metabolize (7(-3)H) testosterone. It is considered that the ingestion of these drugs does not affect tumor mechanisms involving steroids.

Aged↗
PubMed1983

Binding of [3H]-methyltrienolone (R1881) by human breast cancers.

The synthetic radioligand [3H]-R1881 binds to both androgen and progestogen receptors; these two types of receptor activity can be separated by competition experiments with radioinert steroids of defined biological activity. Using two standard tissues, rat prostate and human uterus, which are sources of androgen and progestogen receptors respectively, the optimal conditions for the determination of each type of activity were established. For the purposes of routine assay, androgen receptors were quantified after saturation of progestogen receptor sites with 125 nM radioinert R5020 using [3H]-R1881 and increasing concentrations of radioinert R1881. Progestogen receptor activity could be identified using the same radioligand and competition with radioinert progesterone or R5020, though for routine purposes, progestogen receptors were quantified using the more specific radioligand, [3H]-R5020. The binding of [3H]-R1881 to tumour cytosol was examined in 122 human breast cancers. Seventy-two tumours (59%) showed binding. Androgen receptor activity alone was present in 16 tumours, progestogen receptor activity alone in 30 tumours and both types in 26 tumours. Tumours containing progestogen receptor activity also showed binding to the progestogen [3H]-R5020, whilst those containing androgen receptors alone did not. Androgen receptor concentration varied from 17 to 210 fmol binding sites/mg cytosol protein (mean value 68) and the mean Kd was 2.15 X 10(-9) M. Progestogen receptor concentration varied from 25 to 1350 fmol binding sites/mg cytosol protein (mean value 410) and the mean Kd was 1.35 X 10(-9) M. The biological significance of the presence of these types of receptor in human breast cancers is currently being assessed from clinical follow-up.

Animals↗
PubMed1983

Addictive behaviors and life problems before and after behavioral treatment of problem drinkers.

The broader impact of a behavioral self-control training intervention focusing on the reduction of alcohol consumption was examined in a sample of 93 problem drinkers (55 male). Individual life problems were assessed via the method of goal attainment scaling before and after treatment and at 3-6 months, 12 months and 24 months following termination. Alcohol and drug use, smoking and weight were also evaluated. At intake, women were more likely than men to be unmarried, married to a problem drinking spouse, or taking psychoactive prescription medication but less likely to be using illicit drugs, smoking or gambling . For both men and women negative emotional states and family discord headed the list of current life problems. Although intervention focused primarily on drinking behavior, the majority of other life problems also showed improvement at all follow-up points. Remission of life problems was associated with decreased alcohol consumption. Body weight tended to increase slightly after treatment but typically returned to or below baseline by later follow-ups. Overall rates of drug use and smoking showed little change; however, smoking cessation was associated with successful control or cessation of alcohol use and relapse to smoking coincided with unremitted drinking. Implications for treatment are considered.

Adult↗
PubMed1983

Amount of therapist contact and outcome in a multidimensional depression treatment program.

An 8-week multidimensional program of behavioral management, cognitive restructuring, and assertiveness training was administered to depressed outpatients either individually with a single therapist (n = 12), in two small groups (n = 11), or one large group (n = 11), or as bibliotherapy (n = 12). A randomly assigned waiting list control group was also included (n = 10). Follow-up assessments were conducted at 18 weeks. Principal findings were that 1) there were no significant pretreatment differences among groups, 2) all treated groups including bibliotherapy improved substantially over the course of treatment, 3) the waiting list control group was unchanged during this same period, 4) there were no significant differences among treated groups at termination or at follow-up, nor did these groups change significantly over the period of follow-up. Thus the effectiveness of this multidimensional program was supported, but its efficacy was not systematically influenced by amount of therapist contact.

Adult↗
PubMed1983

Classification of human breast cysts according to electrolyte and androgen conjugate composition.

One hundred human breast cyst fluids have been analysed for sodium (Na+), potassium (K+) and dehydroepiandrosterone (DHA) sulphate. Concentrations varied greatly between individual cyst fluids, Na+ from 20 to 185 mmol/l, K+ from 5 to 160 mmol/l and DHA-sulphate from 1.5 to 87 mumol/l. Analysis of the inter-relationships between Na+, K+ and DHA sulphate revealed two major sub-populations of cyst fluids--one group in which Na+ levels were markedly in excess of K+ and DHA sulphate concentrations were low and the other in which K+ was the predominant cation and DHA sulphate concentrations were high.

Androgens↗
PubMed1982

Discriminant analysis and the selection of patients for controlled drinking programs: a methodological note.

The criterion group classification scheme commonly used in conjunction with discriminant function analysis places individuals in the group for which their membership probability is the highest. This optimizes the proportion of correctly classified cases. The clinical utility of a discriminant based scheme may, however, be underestimated if the proportion of correctly classified cases is the only concern. For clinical purposes, attention must also be paid to minimizing serious diagnostic errors and to improving predictions for individuals. Clinicians can address these concerns by considering membership probabilities for each criterion group of interest. The utility of this approach is illustrated using data from a study in which discriminant analysis was used to identify the characteristics of problem drinkers who abstained, controlled their drinking, or continued to drink heavily after treatment.

Alcohol Drinking↗
PubMed1982

Cellularity and the quantitation of estrogen receptors.

Fifty estrogen receptor (ER)-positive breast cancers have been studied to determine the best way of correcting for differences in cellularity when expressing ER concentration. ER concentration expressed on wet weight and tumour cytosol protein bases showed a positive correlation with tumour cellularity. In contrast, ER concentrations expressed on a DNA basis were not significantly related to cellularity. Although such a mode of correcting for differences in cellularity was imperfect, it did yield a receptor concentration which was less dependent upon tissue cellularity and which may reflect more accurately the inherent receptor status of the tumour cells.

Breast Neoplasms↗
PubMed1982

The relation of plasma androgen levels to sexual behaviors and attitudes of women.

Four androgens: dehydroepiandrosterone (DHEA), androstenedione (A), testosterone (T), and dihydrotestosterone (DHT), a variety of sexual behaviors and attitudes, and several moods were determined regularly in two groups of healthy, married women who differed by three decades in age. The younger women exhibited significantly higher levels of each androgen, the differences being almost entirely attributable to ovarian failure in the older group. Although the older women reported the same levels of sexual desire and sexual arousal as the younger women, their intercourse frequencies and self-rated sexual gratification scores were significantly lower than the values obtained for the younger wives. One or more of the androgen levels related significantly and in the expected direction to each stage of the four-stage sexual response process. Global measures of so-called "sexual adjustment" and estimates of anxiety, depression, and hostility feelings experienced by these women did not relate significantly to any of the four androgen levels.

Adult↗
PubMed1982

Androgen conjugates in human breast cyst fluids.

Dehydroepiandrosterone sulfate (DHAS) has been measured by radioimmunoassay in 100 breast cyst fluids obtained from 82 women. Values ranged from 1.5 to 1,155 microM with a median of 140 microM. These concentrations are in excess of those for plasma but are comparable or less than values for breast secretions obtained by nipple aspiration. Levels of DHAS in cyst fluid were not significantly affected by age, menopausal status, or parity of the subject or by the volume of cyst fluid obtained. In patients with multiple cysts, DHAS values from cysts aspirated from the same breast on the same data were relatively comparable, but wide variations were frequently observed between cysts aspirated on different occasions from the same breast and between cysts from different breasts of the same patient, whether sampled simultaneously or sequentially. Such variability must complicate comparative studies among women.

Adult↗
PubMed1982

Significance of aromatase activity in human breast cancer.

The significance of in vitro aromatization of [7 alpha-3H]testosterone to estradiol by human breast cancer has been investigated by correlation with (a) estrogen receptor activity and (b) clinical response to endocrine therapy. Evidence for estradiol synthesis was obtained in 66 and estrogen receptor activity in 81 of 110 tumors. Whereas most estrogen receptor-positive tumors synthesized estradiol, the majority of the receptor-negative tumors did not. This tendency for aromatization to be associated with estrogen receptor-positive tumors was statistically significant (p less than 0.005). Mean level of receptor was also significantly higher in tumors with aromatization than in tumors without estradiol synthesis (p less than 0.001). Forty patients with advanced breast cancer have been treated by endocrine therapy. There was a significant trend for tumors with aromatization to be associated with response to treatment (p less than 0.05), but the correlation was not absolute and may simply reflect the association between aromatase activity and estrogen receptors. Within the small subgroup of patients treated with aminoglutethimide or adrenalectomy, tumors with high aromatase activity responded whereas those without aromatization did not. Tumor estrogen biosynthesis may therefore be of clinical significance in selecting patients for treatments which remove sources of precursor for aromatization of inhibit aromatase activity itself.

Adrenalectomy↗
PubMed1981

Factors affecting dehydroepiandrosterone sulphate levels in human breast secretions.

Human breast secretions as collected by nipple aspiration have been analysed for dehydroepiandrosterone sulphate by radioimmunoassay. All secretions collected from non-lactating normal women contained remarkably high levels of dehydroepiandrosterone sulphate as compared with plasma taken at the same time. Although there was a large range of concentrations, levels were of a similar magnitude in different ducts from the same breast and in different breasts from the same individual. No significant difference was detected between secretions from pre and postmenopausal women. Sequential sampling of breast secretions through the menstrual cycle in two normal premenopausal women showed no cyclic variation in dehydroepiandrosterone sulphate concentration. There was also no significant difference between levels in breast secretions obtained from normal women and patients with either malignant or benign breast disease. Analysis of secretions from tumour and non-tumour bearing breasts in cancer patients failed to show consistent differences although, in contrast to normal women, the variation between breasts in individual patients was often marked.

Adult↗