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This review discusses some of our recent studies on rat basophilic leukaemia (RBL) cells, a model cell line for mast cell function. Our interest in these cells is a consequence of the role played by mast cells in the allergic response. Thus far we have described the identification of several spots, and their pI/M(r) co-ordinates. Here we describe how we can further decipher the mast cell proteome using a variety of staining/immuno-blotting procedures. We demonstrate the sensitivity of staining procedures and immuno-blotting using an anti-phosphotyrosine antibody. Our aim is to contribute to the ever-expanding two-dimensional gel and phosphoprotein databases currently available.

Background: We examined the effects of disulfiram versus placebo on cocaine dependence in buprenorphine-maintained subjects., Methods: Opioid and cocaine dependent subjects (n = 20) were induced onto buprenorphine maintenance, then randomized to disulfiram (250 mg q.d. ; n = 11) or placebo (n = 9) treatment for 12 weeks., Results: Groups were comparable at baseline on demographic measures and on baseline measures of drug-use severity. Fifteen subjects completed the study, including 8 subjects randomized to disulfiram (72.7%) and 7 subjects randomized to placebo (77.8%). The total number of weeks abstinent from cocaine was significantly greater on disulfiram versus placebo (mean +/- SD: 7.8 +/- 2.6 vs. 3.3 +/- 0.5, p <.05) and the number of days to achieving 3 weeks (24.6 +/- 15.1 vs. 57.8 +/- 7.7, p <.01) of continuous cocaine abstinence was significantly lower in disulfiram compared with placebo. The number of cocaine-negative urine tests during the trial were also higher on disulfiram (14.7) than on placebo (8.6); furthermore, subjects in the disulfiram group achieved consistently higher rates of cocaine-negative urine tests in each 3-week interval and the increase over time was faster in the disulfiram compared with placebo., Conclusions: This preliminary study suggests the potential efficacy of disulfiram versus placebo for treatment of cocaine dependence in buprenorphine-maintained patients.

The Yale Adherence and Competence Scale (YACS) is a general system for rating therapist adherence and competence in delivering behavioral treatments for substance use disorders. The system includes three scales measuring 'general' aspects of drug abuse treatment (assessment, general support, goals of treatment), as well as three scales measuring critical elements of three treatments that are frequently implemented as control or comparison treatments in clinical research in the addictions (clinical management (CM), twelve step facilitation (TSF), and cognitive behavioral therapy (CBT)). Validation of the YACS using data from a randomized clinical trial indicated that the scales have excellent reliability, factor structure, concurrent and discriminant validity. Correlations between adherence and competence scores within scales were in the moderate range, indicating independence (and thus nonredundancy) of these dimensions. Strategies for using the YACS in both psychotherapy and pharmacotherapy research in the addictions are described.

Rigorous clinical trials have been criticized as having limited external validity, and specifically that subjects participating in clinical trials are not representative of individuals seen in clinical practice. To assess the representativeness of subjects participating in clinical trials, 243 research subjects participating in clinical trials of treatments for cocaine dependence were compared to a sub-sample of 213 individuals being treated for cocaine dependence in outpatient clinical settings from a large national database. The data suggest that research findings are not invariably based on less challenging patients with mild forms of substance dependence and related problems; moreover research patients may be similar to, if not more severe than, individuals with cocaine problems seen in regular clinical settings in the community.

This study tested the effectiveness of fluoxetine as a treatment for depression in a population of methadone-maintained opioid addicts. Methadone-maintained opioid addicts (44) with depression received fluoxetine or placebo in addition to their methadone, in a double-blind randomized trial, for 12 weeks. Depressive symptoms decreased significantly overall with no significant differences between the groups treated with fluoxetine versus placebo. In addition, drug use outcomes, including cocaine and heroin self-reported use and urine toxicology were measured. There was a significant decrease in heroin use in treatment, but no medication effect. Cocaine use, was unchanged from pre-treatment to endpoint. In separately analyzing data for the subsample of subjects with the most severe depression, there was a significant decrease in depression during treatment and a significant decrease in self-reported cocaine use, but no medication effect on either depressive symptoms or on cocaine use. This study suggests that fluoxetine is not an effective agent in treating depression or cocaine use in this population.

Despite the historical importance of tolerance and withdrawal in the substance abuse nomenclature, empirical evaluations of tolerance and withdrawal relative to other, non-physical, dependence criteria have been infrequent. Based on data from 521 subjects from a newly completed survey evaluating proposed options for DSM-IV substance use disorders, we found, first, across classes of drugs, requiring tolerance or withdrawal had little effect on rates of dependence, as most subjects who met dependence criteria for each drug class also reported tolerance. Second, tolerance and withdrawal did not emerge as superior to the other dependence criteria on several indicators of concurrent and predictive validity, including severity.