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Biomedical subjects

W R Miller

Publications and source records attributed to W R Miller.

At least 235 records · Page 13Linked to original sources

Techniques to modify hazardous drinking patterns.

There is an enormous empirical literature evaluating and comparing the effectiveness of the many available intervention techniques for alcohol abuse. This chapter is restricted to a description and evaluation of methods designed to modify hazardous drinking patterns at early stages, before the emergence of severe problems and dependence. Thus, the methods described are not limited to interventions with an intended goal of total abstinence. Their common aim is to decrease the quantity and frequency of alcohol consumption to a level at which drinking no longer presents a significant risk to the individual's physical and psychological health. The complete cessation of drinking represents one way in which this can be accomplished, but a more common outcome is moderate and nonproblem drinking.

Alcohol Drinking↗

Fundamental research leading to improved endocrine therapy for breast cancer.

Whilst endocrine therapy has a long-established role in the management of patients with advanced breast cancer, current therapies produce remission in, at best, only between 30 and 40% of cases. The most efficient use of hormonal measures therefore requires the accurate identification of individuals with hormone-responsive tumours. Oestrogen receptor measurements are useful but not fully discriminatory and additional predictive factors are required. Markers, such as specific hormonally induced proteins and mRNA, and antagonistic systems, such as epidermal growth factor receptors and cyclic AMP binding proteins are currently being evaluated. In terms of therapy, surgical manoeuvres such as adrenalectomy and hypophysectomy have already been replaced by the medical administration of anti-oestrogens, progestogens and drug regimes such as aminoglutethimide-hydrocortisone. Although castration by surgery or radiation remains the first-line treatment in premenopausal women with advanced disease, the advent of depot preparations of LHRH agonists offers the opportunity of performing medical ovariectomies which have the added advantage of being reversible. As a result of laboratory studies, more potent anti-oestrogens and more specific "suicide" aromatase inhibitors are entering into clinical practice. These can be expected to increase efficacy of treatment whilst reducing its side-effects. Research using cell-lines of human breast cancer also suggests that anti-progestins and agents capable of antagonizing steroid-induced growth factors will inhibit tumour growth. Such novel therapies potentially could make a major impact in the endocrine management of breast cancer. Lastly, although the primary management of early breast cancer predominantly involves non-hormonal modalities, clinical trials are now providing evidence of survival benefit from adjuvant endocrine therapy. The knowledge accrued from the use of newer endocrine agents in advanced cancer could therefore ultimately be relevant to the treatment of earlier stages of the disease.

Adrenal Cortex Hormones↗

New Roads: assessing and treating psychological dependence.

The "New Roads" approach provides a practical tool for explaining and assessing dimensions of psychological dependence. It connects common triggers for relapse and the effects that the client intends to achieve through substance use. Among its clinical applications are (a) preventive education, (b) assessing high risk situations, (c) tracing pathways of psychological dependence, and (d) devising alternative coping strategies. This simple technique is compatible with a wide range of treatment settings, goals, and approaches.

Adaptation, Psychological↗

Prostaglandins and prognosis in human breast cancer.

Prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha) were measured by gas liquid chromatography--mass spectrometry (glc-ms) in extracts of primary tumours from 78 patients with early breast cancer. These levels have been related to factors of established prognostic value and the patients disease-free interval. Although there was a wide variation in amounts of both prostaglandins extracted from different tumours, no significant relationship was observed between levels of prostaglandins and oestrogen receptors (ER), tumour size, presence of lymph node involvement and disease-free interval following primary treatment. It therefore seems unlikely that the level of these particular prostaglandins within breast carcinomas plays a fundamental role in the prognosis of the disease.

Breast Neoplasms↗

Aromatase activity in breast adipose tissue from women with benign and malignant breast diseases.

In order to determine the significance of local oestrogen biosynthesis within the breast, aromatase activity has been measured in adipose tissue from the breasts of women with either benign (n = 36) or malignant breast disease (n = 51). Particulate fractions from all samples possessed aromatase activity, but levels in adipose tissue adjacent to malignant tumours were significantly higher than those in tissue close to benign breast lesions (P less than 0.0001). Elevated aromatase activity in adipose tissue from breast cancer patients may be of importance in view of the central role played by oestrogen in the natural history of breast cancer.

Adipose Tissue↗

DNA analysis of breast tumour fine needle aspirates using flow cytometry.

Cellular DNA was analysed by flow cytometry in fine needles aspirates (FNA) from both benign and malignant breast lesions in order to determine the feasibility of flow cytometric analysis. In 22 of 26 (84%) benign and 69 of 74 (93%) malignant aspirates, sufficient cells were present to produce good quality DNA histograms. DNA in all 22 benign lesions was diploid. In contrast, of the 69 cancers with sufficient cells for analysis, 40.6% had a diploid DNA content alone, whilst 59.4% had an additional DNA aneuploid line. These results indicate that the majority of FNAs provide sufficient material for flow cytometric analysis of DNA profiles. Such aspirates taken in a sequential manner may also prove to be an ideal method of studying tumour response to therapy.

Adult↗

An immunohistochemical study of the tissue distribution of the breast cyst fluid protein, zinc alpha 2 glycoprotein.

Zinc alpha 2 glycoprotein is one of the proteins present in breast cyst fluids, being found at levels 30-50 times its plasma concentration. Using an immunoperoxidase technique the distribution of this glycoprotein has been studied in a range of non-mammary tissues and carcinomas, as well as in normal, benign and malignant breast specimens. The breast cyst fluid protein was detected in all apocrine cells of skin and in the apocrine metaplastic epithelium lining of breast cysts. A progression was apparent from normal to hyperplastic breast in the number of cells reacting, particularly of cystically dilated acini, to a final consistent staining of apocrine-lined cysts. Zinc alpha 2 glycoprotein was demonstrated in 16 of 33 invasive carcinomas, 15 of which were eosinophilic on haematoxylin and eosin staining, and in one of three non-invasive carcinomas. No staining was apparent in other non-mammary tissues and carcinomas apart from weak reactivity of serous cells of the parotid gland. Zinc alpha 2 glycoprotein is, therefore, a reliable immunohistochemical marker of apocrine cell differentiation.

Apocrine Glands↗

Experimental infection of dogs with Brucella abortus.

Thirteen female dogs, which included eight principals that were fed approximately 4.4 X 10(10) colony forming units (cfu) of Brucella abortus strain 2308 and five sentinels that were housed with the principals, were examined for serologic responses, blood culture, tissue distribution of the organisms and pathologic lesions. Serum samples from each dog were tested on the day of exposure and on post exposure days 5, 7, 10, 14, 21, 28, 35, 42 and 49 for antibodies to B. abortus, using the brucellosis card (BC), standard tube agglutination (STA), 2-mercaptoethanol (ME) and rivanol (RIV) tests. Antibodies were detected in the principals by day 5 and increased through day 21. The STA test was the first to become positive, followed by the BC, ME and RIV tests. After 28 days, the serologic titers receded. From day 14 through day 42, all principals had greater than or equal to 1:50 STA titers. On day 49, seven principals had greater than or equal to 1:50 STA titers and one had a 1:25 STA titer. The sentinels were negative for all tests, except sentinel number 9 which had STA titers ranging from 1:25 to 1:50 on day 14 through day 35. Blood cultures that were obtained from each principal at intervals from one hour after exposure through 49 days were negative. Brucella abortus was isolated from various lymph nodes of the eight principals and from sentinel number 9, which was apparently infected by ingesting brucellae contaminated feces from the principals. Microscopic lesions were not observed in the culture-positive tissues examined.

Animals↗

A human tumour model.

An approach to the management of patients with large (greater than 4 cm) operable breast cancers is described. The conventional sequence of mastectomy followed by systemic therapy is reversed, allowing accurate measurements of response to individual forms of endocrine therapy or chemotherapy. Such a method not only permits individual selection of appropriate systemic therapy, but also allows clinical response to be related to histological and biochemical tumour parameters. A response was observed in eleven of twenty-three patients to endocrine treatment and in twelve of thirteen to combination chemotherapy. In five of the latter the response was histologically complete.

Antineoplastic Combined Chemotherapy Protocols↗

Pulmonary effects of sulfur dioxide and respirable carbon aerosol.

Four-hour individual and combined exposures to 1.0 ppm sulfur dioxide (SO2) and 0.5 mg/m3 (1.5 micron mass median diameter) activated carbon aerosol (ACA) were studied in 20 healthy nonsmoking subjects to determine if activated carbon as a "carrier" aerosol can augment the pulmonary response to SO2. Fifteen-minute exercise stints (VE = 35 liters/min) were performed at commencement and completion of each 4-hr period. Significant increases in nose or throat irritation occurred with the SO2 and SO2 + ACA exposures and in eye irritation with the SO2 + ACA exposure. Small, statistically significant decrements in spirometric function were observed following the first exercise (t = 17 min) for both the SO2 and SO2 plus ACA exposures; no significant changes were associated with the ACA exposure. Comparing function changes between the SO2 and the SO2 + ACA exposures demonstrated no statistically significant differences, thus a lack of SO2 response enhancement by the carbon aerosol. The determination that the activated carbon sorbed only 1% of the SO2 challenge concentration could explain the observed lack of SO2 response enhancement.

Adult↗