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Biomedical subjects

W R Miller

Publications and source records attributed to W R Miller.

At least 91 records · Page 5Linked to original sources
PubMed1999

The community-reinforcement approach.

The community-reinforcement approach (CRA) is an alcoholism treatment approach that aims to achieve abstinence by eliminating positive reinforcement for drinking and enhancing positive reinforcement for sobriety. CRA integrates several treatment components, including building the client's motivation to quit drinking, helping the client initiate sobriety, analyzing the client's drinking pattern, increasing positive reinforcement, learning new coping behaviors, and involving significant others in the recovery process. These components can be adjusted to the individual client's needs to achieve optimal treatment outcome. In addition, treatment outcome can be influenced by factors such as therapist style and initial treatment intensity. Several studies have provided evidence for CRA's effectiveness in achieving abstinence. Furthermore, CRA has been successfully integrated with a variety of other treatment approaches, such as family therapy and motivational interviewing, and has been tested in the treatment of other drug abuse.

Adaptation, Psychological↗
PubMed1998

The primary use of endocrine therapies.

Primary endocrine therapy is potentially superior to primary chemotherapy in patients with ER-positive tumors. The ability to give endocrine therapy perioperatively may be a better test than chemotherapy of the hypothesis that the events accompanying surgery affect prognosis. However, a major problem in all studies of primary endocrine therapy is that there has been no clear experimental test of preoperative versus postoperative therapy. This is because the major thrust of treatment has been in the elderly with the purpose of determining whether surgery can be avoided altogether. The fact that in ER-positive tumors primary endocrine therapy is associated with similar response rates to chemotherapy make it an attractive therapy for older women. This is the group where adjuvant chemotherapy has not been adequately tested (> or = 70 years of age). In contradistinction, adjuvant endocrine therapy shows marked survival benefits in patients with ER-positive tumors in these age groups (Table 1). It appears likely that primary endocrine therapy will allow breast conservation and prognostic information as is seen with chemotherapy. A major question which requires answering is whether primary endocrine therapy will improve survival more than adjuvant therapy alone. Although ER status is a good marker of responsiveness, its specificity, in particular, is not optimal. The ability to assess the dynamic effects of primary endocrine therapy by sequential biopsy and measurement of biological responses to oestrogen deprivation may allow us to predict precisely the patients likely to benefit from treatment. This clinical scenario allows us to use other potentially useful assessments such as the non-invasive estimation of angiogenesis using quantitative imaging techniques of blood flow. The newer anti-estrogens and aromatase inhibitors appear ideally suited to primary therapy since they have rapid and profound inhibitory activities, few or no agonist effects, and low side effect profiles. A preoperative trial of Faslodex is planned by the EORTC and another with Arimidex is under consideration by the ATAC (Arimidex, tamoxifen and combined) Trialist Group (Fig. 7). The precise design of these studies will require considerable thought.

Aged↗
PubMed1998

Growth-inhibitory effects of the synthetic retinoid CD437 against ovarian carcinoma models in vitro and in vivo.

The activity of CD437¿6-[3-(1-adamantyl)-4 hydroxyphenyl]-2-naphthalene carboxylic acid¿, a relatively selective activator of RAR-gamma, was evaluated against four human ovarian-carcinoma cell lines : PE01, PE04 (a Pt-resistant in vivo-derived counterpart of PE01), PE01CDDP (a Pt-resistant in vitro-derived model of PE01) and PE014. Growth inhibition was observed after 3 and 6 days of exposure to sub-micromolar concentrations as assessed by a reduction in cell number. IC50 values against PE01, PE04, PE01CDDP and PE014 were 0.09, 0.21, 0.12 and 0.28 microM (day 3) and 0.1, 0.14, 0.07 and 0.17 microM (day 6), respectively. Cisplatin-resistant cell lines were as responsive as cisplatin-sensitive lines, indicating potential activity in resistant disease. CD437 was also evaluated against the PE04 xenograft grown in nude mice using daily doses of 20 (days 0-4) and 10 mg/kg (days 0-4 and 7-11) given either by i.p. delivery or oral administration. Significant growth inhibition (P < 0.05) was obtained for both doses and by both routes. These data provide further support for the view that retinoids have value for the treatment of ovarian cancer.

Administration, Oral↗
PubMed1998

Community reinforcement and family training (CRAFT): engaging unmotivated drug users in treatment.

Although motivation for drug abuse treatment is a substantial problem, unilateral intervention through concerned significant others (CSOs) represents a promising method for engaging unmotivated individuals. The Community Reinforcement and Family Training (CRAFT) program, based on principles of reinforcement was developed for this specific purpose. In Phase I, CSOs received the CRAFT intervention, whereby they were taught skills for modifying a loved one's drug-using behavior and for enhancing treatment engagement. CSOs were evaluated at 3 and 6 months. In Phase II, engaged drug users received treatment using the Community Reinforcement Approach (CRA). A total of 62 CSOs participated in this evaluation of the effectiveness of CRAFT. CSOs completed, on average, 87% of offered treatment sessions. During the 6-month study period, 74% succeeded in engaging their resistant loved one in treatment. Reported abstinence both from illicit drugs and alcohol increased significantly for drug users engaged in treatment, but not for unengaged cases. All CSOs showed significant reduction in depression, anxiety, anger, and physical symptoms, with average scores dropping into the normal range on all measures. CRAFT provides a promising alternative to confrontational and detachment approaches in counseling CSOs to help their loved ones.

Adolescent↗
PubMed1998

Antitumour activity and schedule dependency of 8-chloroadenosine-3',5'-monophosphate (8-ClcAMP) against human tumour xenografts.

8-Chloroadenosine-3',5'-monophosphate (8-ClcAMP) is a novel antitumour agent currently undergoing phase I clinical trials in several European centres. In this study, its antitumour activity against human tumour xenografts and its dependence on schedule were investigated. When administered by continuous infusion at doses of 100 or 50 mg/kg/day to nude mice bearing human tumour xenografts, 8-ClcAMP inhibited the growth of the HT 29 colorectal, ZR-75-1 breast, HOX 60 and PE04 ovarian and PANC-1 pancreatic carcinoma xenografts. However, these infusion schedules produced hypercalcaemia and severe weight loss. In an attempt to optimise antitumour activity and minimise toxicity, several other schedules were studied. In comparison with continuous administration of 8-ClcAMP at 50 mg/kg/day for 14 days which, although producing complete growth inhibition in the HOX 60 model, was associated with a marked body weight loss, schedules in which the infusion was interrupted (infusion on either days 0-4; 7-11 or days 0-2; 6-8) produced minimal weight loss but also reduced antitumour activity. However, co-administration of salmon calcitonin with continuous infusion of 8-ClcAMP prevented both hypercalcaemia and body weight loss in 3/6 animals while still producing marked inhibition of tumour growth. These data indicate that 8-ClcAMP has broad-spectrum antitumour activity and the major side-effect of hypercalcaemia may at least in part be ameliorated by the use of salmon calcitonin.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

Estrogen regulation of transforming growth factor-alpha in ovarian cancer.

Transforming growth factor alpha (TGFalpha) may be induced by estrogen in estrogen responsive systems and can contribute to the growth-modulatory effects of this hormone. To test whether TGFalpha contributes to estrogen-regulated growth in ovarian cancers, we have compared the effects of 17beta-estradiol (E2) and TGFalpha in a range of ovarian carcinoma cell lines. Addition of E2 to the estrogen receptor (ER)-positive cell lines (PE01, PE04 and PE01CDDP) produced a 2-4 fold increase in TGFalpha protein concentrations in media conditioned by the cells. Both E2 and TGFalpha stimulated the growth of the PE01 and PE04 lines and inhibited the growth of the PE01CDDP line. Furthermore, the E2-mediated growth effects could be reversed by an epidermal growth factor (EGF) receptor-targeted antibody. E2 also down-regulated EGF receptor expression in ER-positive cell lines. In a series of primary ovarian tumors, higher concentrations of ER were associated with an increased percentage of tumors expressing TGFalpha mRNA and a decreased percentage expressing EGF receptor protein. All these data are consistent with E2 increasing production of TGFalpha in ER-positive ovarian cancer and this in turn acting through the EGF receptor to modulate growth in an autocrine manner.

Antibodies, Monoclonal↗
PubMed1998

Clinical importance of intratumoral aromatase.

Evidence to support the contention that estrogen biosynthesis in breast cancers is of clinical significance has been sought by relating activity to (i) clinical response to aromatase inhibitors and (ii) tumor concentrations of estrogens. Significant correlations have been reported between the presence/high levels of tumor aromatase in vitro and likelihood of response to aminoglutethimide in patients with advanced breast cancer, but the association is not absolute and it has been more difficult to demonstrate similar relationships in patients with earlier stages of cancers treated with other more potent inhibitors. There are however data to suggest that in vitro measurements of aromatase may not reflect in situ estrogen synthesis. For example mammary adipose tissue fibroblasts preincubated with reversible aromatase inhibitors may paradoxically display elevated in vitro aromatase activity. Similar enhanced in vitro activity may be observed in breast material taken from patients treated neo-adjuvantly with aromatase inhibitors such as aminoglutethamide and letrozole. That this is an artifact of in vitro systems can be demonstrated by performing in situ assessments of aromatase activity in patients before and after treatment with aromatase inhibitors. Thus it can be shown that letrozole markedly inhibits in situ aromatase and reduces tumor levels of estrogens.

Adipose Tissue↗
PubMed1998

Why do people change addictive behavior? The 1996 H. David Archibald Lecture.

Although there are specialty journals and professions focusing on addictions treatment, the reasons why people change addictive behaviors are still not well understood. The simplistic account that people change because they receive treatment is wanting in many ways. Many people who recover do so without formal treatment. Even relatively brief interventions seem to trigger change, and the dose of treatment delivered is surprisingly unrelated to outcomes. Client compliance with many different approaches, including placebo medication, has been linked to better outcomes. Client outcomes also vary widely depending upon the therapist who delivers treatment. Various models are briefly considered that may help in understanding this intriguing puzzle of change.

Behavior, Addictive↗
PubMed1998

Researching the spiritual dimensions of alcohol and other drug problems.

Although religions have been far from silent on the use of psychoactive drugs, and spirituality has long been emphasized as an important factor in recovery from addiction, surprisingly little research has explored the relationships between these two phenomena. Current findings indicate that spiritual/religious involvement may be an important protective factor against alcohol/drug abuse. Individuals currently suffering from these problems are found to have a low level of religious involvement, and spiritual (re)engagement appears to be correlated with recovery. Reasons are explored for the lack of studies testing spiritual hypotheses, and promising avenues for future research are discussed. Comprehensive addictions research should include not only biomedical, psychological and socio-cultural factors but spiritual aspects of the individual as well.

Alcoholism↗
PubMed1998

Special populations in Alcoholics Anonymous.

The vast majority of Alcoholics Anonymous (AA) members in the United States are white, and only a few studies have investigated the program's effectiveness for ethnic minorities. Project MATCH, a multisite research study aimed at developing guidelines for assigning alcoholics to appropriate treatment approaches, also assessed AA effectiveness for minority clients. Some differences in AA attendance existed among white, African-American, and Hispanic Project MATCH participants who had received some inpatient treatment before entering the study, but not among participants who had not received inpatient treatment. Further analyses of white and Hispanic Project MATCH participants demonstrated that although Hispanic clients attended AA less frequently than white clients, their involvement with and commitment to AA was higher than among white clients. For both Hispanics and whites, AA involvement predicted increased abstinence.

Black or African American↗
PubMed1998

Functionality of the progesterone receptor in ovarian cancer and its regulation by estrogen.

Here, we sought to obtain evidence that the progesterone receptor (PR) may be functional in ovarian cancer and regulated by estrogen. Megestrol acetate inhibited growth of the PR-positive PE04 ovarian carcinoma xenograft but not the PR-negative HOX 60 xenograft. PR concentration was higher in early-stage (I/II) tumors than in advanced-stage (III/IV) tumors (P = 0.007) and in tumors of endometrioid histology compared to other carcinoma subtypes (P = 0.009). Patients with a tumor PR concentration of >40 fmol/mg protein had significantly improved survival over those patients whose tumors contained <40 fmol/mg (P = 0.0007; log-rank). Evidence of PR regulation by estrogen was obtained by endocrine manipulation of the PE04 xenograft. PR content of PE04 xenografts fell from 145 to 7 fmol/mg protein in ovariectomized mice and was 2 fmol/mg in male mice. Administration of 17-beta-estradiol increased PR content to 745 fmol/mg. In primary ovarian carcinomas, PR was significantly associated with ER concentrations (P < 0.0001), suggesting regulation of PR levels by estrogen. This association was present for tumors of endometrioid histology (P < 0.0001) but not for those with serous histology (P = 0.31). These data point to the regulation of PR levels by estrogen in ovarian cancer and to a mediatory role for PR in the inhibition of growth induced by progestin.

Animals↗
PubMed1997

Solid-phase extraction and high-performance liquid chromatographic determination of tamoxifen and its major metabolites in breast tumour tissues.

A sensitive (200 ng/g) and selective reversed-phase high-performance liquid chromatography separation has been developed to determine the levels of tamoxifen, 4-hydroxytamoxifen (4-OH) and desmethyltamoxifen (DMT) in tumour tissue taken from patients undergoing tamoxifen therapy. A muBondapak C18 10 microm column (30 cm x 3.8 mm I.D.) was used, with a mobile phase of methanol-1% triethylamine at pH 9 (89:11, v/v). Sample preparation was carried out using a C2 (500 mg sorbent, 3 ml reservoirs) solid-phase extraction method, and extraction efficiencies were followed in individual extracts using a [3H]TAM radiolabelled spike (10000 dpm), with a range of 60-90%. Accuracy and precision (standard deviation) as determined from tumour spiked with radioinert tamoxifen and its metabolites ranged from 83.4-92.3% (+/-23-33%) at 20 microg/g; 85.2-87.7% (+/-18-23%) at 2 microg/g; 88-101% (+/-15-50%) at 0.2 microg/g and 63-94% (+/-13-24%) at 0.02 microg/g. Results from seventy-two patients show mean values (+/-S.D.) of 174+/-203 ng/g for 4-OH; 783+/-1326 ng/g for DMT and 410+/-458 ng/g for TAM, variations reflecting heterogeneity in levels between patients. This methodology can be routinely applied to the determination of tamoxifen and its metabolites in tumour tissues from patients undergoing tamoxifen therapy.

Antineoplastic Agents, Hormonal↗
PubMed1997

Gender and patterns of alcohol problems: pretreatment responses of women and men to the comprehensive drinker profile.

Gender differences were analyzed in a sample of 233 (83 women, 150 men) problem drinkers treated at the same clinic. Demographic and family history measures showed few gender differences. Men reported more alcohol consumption than did women, but patterns of drinking and intoxication levels were similar. Males reported drinking and intoxication at an earlier age, more beer and less wine drinking and more drinking away from home and driving after drinking. Women reported more negative emotional effects of drinking and more spouses with alcohol problems. Despite similar problem duration, men showed more lifetime alcohol problems but not dependence signs. Men were more likely to accept a disease concept of alcoholism. Rates of smoking, other drug use, and other life problems were similar.

Adult↗
PubMed1997

Treatment approaches for pathological gamblers.

Outcome literature on the treatment of pathological gambling is reviewed, encompassing psychodynamic, behavioral, cognitive, cognitive-behavioral, multimodal, pharmacotherapeutic, and 12-step approaches. No properly controlled research has been conducted with psychodynamic or 12-step methods, and pharmacotherapies require replications with larger samples to determine their efficacy. Multimodal approaches have been tested most often in inpatient settings, and given the range of methods combined it is difficult to infer specific efficacy for treatment components. The largest volume of outcome research has focused on behavioral, cognitive, and combined cognitive-behavioral treatment methods, and findings from controlled and uncontrolled trials provide support for efficacy of these approaches. As a whole, the literature indicates that pathological gambling can be treated with highly successful outcomes. Needs for further research are considered.

Behavior Therapy↗
PubMed1997

Steroid hormones and cancer: (III) observations from human subjects.

Epidemiological evidence strongly suggests that steroid hormones are implicated in the risk of cancers of the breast, ovary and endometrium. However, it has proved difficult to implicate specific hormones or show that measurement of circulating hormones can identify women who will go on to develop malignant disease. There are, however, more convincing data that a proportion of established cancers are dependent upon steroid hormones for their continued growth and these underpin the use of endocrine manoeuvres in the treatment of these malignancies. Increased knowledge of the synthesis, release and mechanism of action of steroid hormones has led to the development of novel therapies for endocrine sensitive cancer and on-going research can reasonably be expected to identify tumour markers which can accurately predict hormone-dependency and provide better understanding of the mechanism by which response and resistance to therapy occur. The hope is that this knowledge will translate into more effective and rational endocrine treatment benefiting increased numbers of patients.

Antineoplastic Agents, Hormonal↗