Treatment for alcohol-abusing workers.
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Alcoholics Anonymous↗
Biomedical subjects
W R Miller
Publications and source records attributed to W R Miller.
The effectiveness of treatment for substance abuse. Reasons for optimism.
Reviews of treatment research have sometimes drawn gloomy conclusions which clash with the experience of clinicians. Yet the same literature provides reasons for optimism about the future of substance abuse treatment. There are treatment strategies with encouraging evidence of effectiveness that are only beginning to be applied in practice. Furthermore, research is clarifying the mechanisms and reasons for successful treatment, pointing to factors to be emphasized in therapy. Approaches that yield even short-term advantages can promote more rapid recovery, and may provide clues for how to prevent relapse. In difficult economic times, hope is also provided by evidence that even relatively brief treatment can be substantially more effective than none at all. Recent evidence also supports the importance of matching clients to alternative treatment strategies. To the extent that practitioners can keep abreast of such developments and adjust their clinical work accordingly, there is reason to believe that the effectiveness of substance abuse treatment can be greatly increased.
Alcoholism↗
Mitogenic effects of epidermal growth factor and transforming growth factor-alpha on EGF-receptor positive human ovarian carcinoma cell lines.
The role of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) in the growth modulation of three human ovarian adenocarcinoma cell lines, PEO1, PEO4 and PEO14, has been examined by measuring responses of the cells growing in monolayer culture to exogenous addition of the growth factors. The presence of EGF receptors in the cell lines has been confirmed by ligand binding and immunocytochemical staining using a monoclonal antibody directed against the EGF receptor. The growth of all three cell lines was stimulated by both EGF and TGF-alpha. Dose-response effects were noted with the greatest growth stimulation occurring at concentrations between 0.1 and 10 nmol/l. The stimulatory effects of EGF and TGF-alpha were accompanied by changes in the cell cycle distribution as detected by flow cytometric analysis. It is concluded that EGF and TGF-alpha are important growth regulators in these EGF-receptor positive ovarian cancer cells.
Adenocarcinoma↗
Transforming growth factor-beta mRNA expression and growth control of human ovarian carcinoma cells.
The pattern of TGF beta expression and in vitro response to TGF beta has been defined in three ovarian carcinoma cell lines (PEO1, PEO4 and PEO14). Marked differences in both mRNA expression and growth responses were detected between the cell lines. All expressed mRNA for TGF beta 3, PEO1 and PEO4 but not PEO14 expressed mRNA for TGF beta 1, whereas PEO14 but not PEO1 and PEO4 expressed TGF beta 2. Growth of PEO14 cells in culture was markedly inhibited by both TGF beta 1 and beta 2. PEO1 cells were inhibited by TGF beta 1, but not TGF beta 2 whilst growth of PEO4 cells were not affected by exposure to either of these peptides. These data indicate that several elements of potential autocrine loops involving TGF beta's are present within ovarian cancer cells.
Cell Cycle↗
Growth control by epidermal growth factor and transforming growth factor-alpha in human lung squamous carcinoma cells.
Although EGF receptor expression is generally elevated in human lung squamous carcinoma, the biological significance of this phenomenon and the role of EGF and TGF-alpha in this disease are poorly understood. We have investigated three human lung squamous carcinoma cell lines (NX002, CX140 and CX143) and have shown, using an antibody (EGFR1) directed against the EGF receptor, that the majority of cells in all three lines express the EGF receptor. Using a ligand binding assay, Scatchard analysis indicated high concentrations (1,300-2,700 fmol mg-1 protein) of a single low affinity binding site (Kd = 3-5 nM) within these lines. Addition of EGF or TGF-alpha at concentrations greater than 0.1 nM resulted in growth inhibition of all three lines and this was associated with an accumulation of cells in the G2/M phase of the cell cycle. Growth inhibitory effects were not explained by an enhancement of cellular differentiation as monitored by involucrin expression and the ability to form cornified envelopes. While the presence of EGF could not be detected in medium conditioned by the NX002 cell line, mRNA for TGF-alpha was detected in all three lines suggesting the possibility of an autocrine loop. These results together with reports of growth inhibition by EGF and TGF-alpha in other systems suggest that EGF and similar molecules might have a growth regulatory role in lung cancer cells and modulation of such may have therapeutic potential.
Carcinoma, Squamous Cell↗
12-O-tetradecanoylphorbol 13-acetate induced differentiation in human lung squamous carcinoma cells.
Three human lung squamous carcinoma cell lines (NX002, CX140 and CX143) demonstrate features of squamous differentiation including involucrin synthesis and competence to form cornified envelopes. 12-O-Tetradecanoylphorbol 13-acetate inhibits growth of these cell lines and this growth inhibition is associated with enhanced differentiation.
Antigens, Neoplasm↗
Prognostic factors in breast cancer.
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Breast Neoplasms↗
Acute myocarditis in fulminant systemic sclerosis.
Myositis and myocarditis have been reported in progressive systemic sclerosis, and these patients have had favorable therapeutic responses to intravenous pulse methylprednisolone. Thus far, premortem biopsy documentation of myocarditis and myocardial fibrosis has not been reported in such patients. We report the case of a patient with subacute congestive heart failure six months after she developed Raynaud's phenomenon. Clinical examination was typical of scleroderma but there was no proximal muscle weakness. She had elevated creatine kinase and MB-creatine kinase and laboratory evidence of hypothyroidism. Echocardiogram demonstrated four-chamber dilatation and severe left ventricular dysfunction. Cardiac catheterization revealed normal epicardial coronary arteries and severely decreased cardiac index. A skin biopsy specimen of the forearm was consistent with diffuse systemic sclerosis, and an endomyocardial biopsy specimen demonstrated mild fibrosis and lymphocytic infiltrate. Her heart failure initially improved with digoxin, furosemide, and enalapril. She also received L-thyroxine and intravenous methylprednisolone. The heart failure progressed over the next six weeks and she died. Patients with scleroderma and new-onset heart failure may have acute myocarditis.
Acute Disease↗
Long-term follow-up of behavioral self-control training.
Four samples of problem drinkers treated by behavioral self-control training were evaluated at 3.5, 5, 7 and 8 years following treatment, respectively. Of 140 cases, 99 (71%) were accounted for: 23 abstinent, 14 with controlled and asymptomatic drinking, 22 improved but still impaired, 35 unremitted and 5 deceased. Abstinent versus controlled-drinking outcomes were most strongly differentiated by pretreatment severity of alcohol problems and dependence and by the patients' pretreatment self-assessment and goals. Percentages of abstainers and of relapsed cases increased at long-term follow-ups. A reasonably constant percentage of known outcomes (14%) were clearly controlled and asymptomatic drinkers in each of the follow-up samples. Most of the long-term controlled drinkers had established this pattern within the first year following treatment. However, periods of controlled drinking during the first year did not reliably predict maintenance of this pattern. Successful asymptomatic drinkers were discriminable from other outcomes based on pretreatment characteristics.
Adaptation, Psychological↗
Using biological measurements, can patients with benign breast disease who are at high risk for breast cancer be identified?
In order to address the question of whether biological measurements might identify women with benign breast disease (BBD) at particular risk for breast cancer, analyses were performed on cyst fluids aspirated from patients presenting with palpable breast cysts. Electrolyte profiles showed that cyst fluids may be divided into major subpopulations which differ in terms of histological appearance of cyst lining epithelium, pattern of cyst presentation, and levels of other fluid constituents such as androgen conjugates and epidermal growth factor. Analysis of cyst fluids from 18 patients who subsequently developed breast cancer 1 to 8 years later showed that 12 individuals had group A cysts, three had group B cysts, and three presented with a mixture of the two types. Therefore, although this represents an increased proportion of group A cysts as compared with the total population of cyst fluids studied over the same time period, individuals subsequently developing breast cancer were not confined to one subgroup of cysts. Androgen conjugate and growth factor content also did not predict for subsequent cancer. At the present time, it is therefore concluded that biochemical measurements in cyst fluids cannot accurately identify women likely to develop breast cancer. However, the routine aspiration of cysts does provide the opportunity to monitor the local microenvironment of the breast.
Androgens↗
The Helpful Responses Questionnaire: a procedure for measuring therapeutic empathy.
The development and evaluation of a measure of accurate empathy is described. The Helpful Responses Questionnaire (HRQ) is a brief free response questionnaire that can be administered to groups. Interrater reliability coefficients for items range from .71 to .91, and reliability for total HRQ scores was found to be .93. HRQ scores rose significantly following a 2-day workshop on active listening and crisis intervention skills offered in 14 communities. Normative data are reported based on a sample of 190 paraprofessional trainees. Level of empathy was found to be modestly related to respondents' self-esteem.
Adult↗
Mutagens in human breast cyst fluid.
Cyst fluids aspirated from patients presenting with palpable cysts of the breast were analysed for mutagenic activity, as determined by the Ames test. Of the 439 women studied, 9.6% had mutagen-positive fluids. There was no obvious relationship between the presence of mutagen-positive fluids and clinical or epidemiological details of the women from which they were obtained. Preliminary characterisation of the mutagenic activity suggested that the responsible agents have diverse chemical properties.
Adult↗
Factors influencing the response of MCF-7 cells to an agonist of luteinising hormone-releasing hormone.
To clarify the mechanism by which the luteinising hormone-releasing hormone agonist, buserelin, may have direct effects on breast cancer cells, factors potentially influencing its action have been studied in the MCF-7 breast cancer cell line. Oestradiol and epidermal growth factor (EGF), which stimulate the growth of MCF-7 cells in culture, reversed, at least in part, the inhibitory effects of buserelin. Insulin also abolished growth inhibition. Quantitative effects of buserelin differed according to the batch of fetal calf serum used as media supplement. These data suggest that the direct inhibitory effects of buserelin on breast cancer cells are mediated at least in part by an antagonism of growth-promoting factors.
Breast Neoplasms↗
Zinc alpha-2 glycoprotein levels in serum and breast fluids: a potential marker of apocrine activity.
Zinc alpha-2 glycoprotein (ZnGP) was measured in human breast microcysts, breast secretions, breast cyst fluid and serum. Detectable amounts of ZnGP were found in all fluids but the highest levels were found in microcysts. Apocrine macrocysts had a higher ZnGP level than flattened macrocysts. In both cysts and secretions levels of ZnGP correlated with those of dehydroepiandrosterone sulphate. Levels were significantly higher in cyst fluids from women who developed further cysts during follow-up compared with those in fluid from women who did not. Concentrations of ZnGP in serum from breast cancer patients were significantly higher than controls but not women with breast cysts. Women with node positive breast cancer had higher serum levels compared with those in node negative patients. Women with more advanced breast cancer had higher serum ZnGP levels than those with earlier disease. ZnGP is a serum and breast marker of apocrine activity and may prove to be a useful prognostic marker in breast cancer.
Apocrine Glands↗
Warm turkey: other routes to abstinence.
The requirement of immediate and abrupt quitting ("cold turkey") can be an obstacle to the acceptance and accomplishment of abstinence as a long-term outcome. Three alternative "warm turkey" routes to abstinence are discussed: (a) sobriety sampling, (b) tapering down, and (c) trial moderation. Clinical research evidence and case examples are provided in support of these alternative approaches.
Adult↗
Aromatase activity in breast tissue.
Aromatase activity may be detected both in breast adipose tissue and breast cancer in levels similar to or greater than those in other peripheral tissues. Factors influencing such local biosynthesis have been sought. Of 247 primary breast cancers investigated, 178 showed evidence of oestrogen biosynthesis. No significant relationships were found between either the presence or levels of activity and tumour histopathology, patient characteristics (such as age and menopausal status), disease stage and prognosis (determined by disease-free interval and survival after primary treatment). Aromatase was more likely to be found in cellular cancers and those which were oestrogen receptor-positive, but these were not absolute associations, activity being detected in tumours with all degrees of cellularity and both receptor-positive and receptor-negative cancers. However, in a small group of patients with metastatic oestrogen receptor-positive tumours, response to the aromatase inhibitor, aminoglutethimide, seemed confined to tumours with aromatase activity. Oestrogen biosynthesis was detected in all specimens of breast adipose tissue examined. Activities were higher in fat from breast cancer patients compared with that from women with benign breast disease. In breasts with cancer, levels were higher in quadrants bearing tumour compared with those without evidence of malignancy. It is suggested that either enhanced aromatase in breast fat promotes the appearance of overt cancer or tumour factors induce aromatase in surrounding fat. Finally, although no significant correlations were detected in postmenopausal women between local aromatase activity and endogenous oestrogens in breast cancer, perfusion studies show that in situ oestrogen biosynthesis is primarily responsible for oestrogen levels in the majority of breast tissues. These data suggest that local aromatase activity may influence events within the breast and may be associated with the natural history and progression of certain malignancies.
Adipose Tissue↗
Characterisation and properties of a small cell lung cancer cell line and xenograft WX322 with marked sensitivity to alpha-interferon.
Controversy exists as to whether interferons usefully influence the growth of epithelial carcinomas. A small cell lung carcinoma (SCLC) cell line, WX322, has been derived which is greater than 1000-fold more sensitive to alpha-interferon (IFN) when grown in agar than other reported SCLC cell lines. The WX322 line has been characterised to prove its epithelial origin and its chemosensitivity compared with that of the NCI-H69 small cell line. The WX322 cell line expresses neuroendocrine and epithelial markers and possesses a morphology consistent with SCLC origin. A concentration of 5 IU ml-1 of IFN produced 50% inhibition of colony formation in agar in the WX322 line, whereas a concentration of greater than 10(5) IU ml-1 was required to produce a comparable effect with the NCI-H69 cell line. In contrast, WX322, possessed similar sensitivity to NCI-H69 cells when exposed to a range of cytotoxic agents. Analysis of the cell cycle indicated that IFN increased the percentage of cells in the G0/G1 phase for the WX322 cell line but increased the percentage in S phase for the NCI-H69 line. Growth of the xenograft, from which the cell line was derived, was also inhibited by IFN at doses greater than 10(5) IU/mouse/day. The WX322 cell line whether grown in agar or as a xenograft shows an unusually high sensitivity to IFN and provides an interesting model for studying mechanisms of IFN cytotoxicity to epithelial cells.
Animals↗
Growth inhibition observed following administration of an LHRH agonist to a clonal variant of the MCF-7 breast cancer cell line is accompanied by an accumulation of cells in the G0/G1 phase of the cell cycle.
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Breast Neoplasms↗