Recent developments in the pharmacotherapy of alcohol dependence.

The effectiveness of a treatment for alcohol dependence can be appropriately determined only after controlling for the usual clinical course of alcoholism, subgroups of alcohol-dependent individuals, and placebo effects. The results of appropriate treatment trials must also be interpreted in light of the side effects and costs, and there must be assurances that the overall improvement in functioning observed with the drug is significant enough to outweigh the liabilities. In addition, medications are almost always used in combination with education, counseling, and behavioral therapies, and the impact of these additional treatments must be considered. Viewed from this perspective, 3 medications are quite promising regarding their potential future impact in the alcohol field, including naltrexone, the medication with the most available data in the United States. There are additional data regarding buspirone and acamprosate. Intriguing results have also been generated regarding medications that affect serotonin and dopamine brain activity and with alcohol-sensitizing drugs such as disulfiram. However, none of these medications has been proven to be clinically effective in the routine treatment of the average alcoholic… (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Thinking about thinking

BACKGROUND: The nursing leadership at a 900-bed tertiary-care facility in the southeast believed an opportunity existed to improve the critical thinking abilities of the professional nursing staff. METHOD: A team, consisting of a diversified group of nurse educators and managers, had the opportunity to gain understanding of the critical thinking process of the nursing staff as well as to develop a plan designed to improve critical thinking skills. RESULTS: Outputs of the team included development of a critical thinking model and process as well as an action plan that specifically outlined how it would implement the model within the organization using a preceptor-based educational process. CONCLUSION: Nursing leadership within this facility believes that nurturing critical thinking in the staff will have a positive impact on care delivery outcomes. Creating shared visions through the assumptions that the staff and organization hold is important to improving care provided. Assisting staff with using a critical thinking process in order to construct, tear down, and then reconstruct clinical incidents as encouraged by this model is one key to problem-solving.     

New thoughts about thinking.

Reviews the book, The Nature of Thought: Essays in Honor of D.O. Hebb edited by P.W. Jusczyk and R.M. Klein (1980). The phenomenon of thinking, the topic to which this important collection of essays is addressed, is one of the principal perennial concerns of psychology. It is as fundamental and as unsolved a problem today as at the time of experimental psychology's introspectionist beginnings and, through the ensuing decades, has never ceased to stimulate, fascinate, baffle, and bewilder the serious student of psychological phenomena. The present volume appropriately reflects a wide spectrum of specific concerns and approaches to this topic. Appropriate, as well, is its dedication in honour of D.O. Hebb, whose own approach to the study of thought is especially broad and encompassing. The book resulted from a recent series of lectures, in Hebb's honour, at Dalhousie University. This is not, however, a volume primarily addressed to Hebb's ideas. Rather, it is a collection of progress reports by a number of distinguished researchers in the fields of human and animal cognition on recent approaches to topics such as consciousness, mental imagery, problem solving, representation, attention, and skilled performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Advance thinking about advance directives

Stilboestrol tablets (20 x 1 mg) were given to 4 ostriches. Urine was collected over a period of 8 days and stored frozen at-20 degrees C pending analysis. Analyses were performed on a gas chromatograph-mass selective detector for the presence of parent compound and/or metabolites. Diethylstilbestrol and its metabolite, dienestrol, were detected in urine; dienestrol only for 1 day but diethylstilbestrol for 8 days after administration. Residue analysis for the use of diethylstilbestrol as growth promoter can be performed on the urine of ostriches by scanning for parent compound only since it can be detected longer than the metabolite.     

Meta-analysis of the effects of alcohol dehydrogenase genotype on alcohol dependence and alcoholic liver disease

The purpose of this paper is to assemble and evaluate existing data on the effect of genetic variation in ADH2 and ADH3 on the risk of alcohol dependence, and on the risk of alcoholic liver disease. Calculations of odds ratios and their confidence limits, and tests for heterogeneity of the results from the available studies, have been performed. It is clear that possession of the ADH2-2 allele decreases the risk of alcohol dependence, but it increases the risk of alcoholic liver disease among alcoholics. ADH3 variation also has significant effects on alcohol dependence, which may be due to linkage to ADH2; the ADH3 effect differs significantly between Asian and European subjects. Therefore ADH genotype has substantial effects on risk of alcohol dependence and alcoholic liver disease, but more work is needed on the generalizability of these findings to non-Asian populations, and on possible mechanisms.     

Personality and the genetic risk for alcohol dependence.

The extent to which the genetic risk for alcohol dependence (AD) and conduct disorder (CD) and their common genetic risk overlap with genetic factors contributing to variation in dimensions of personality was examined in a study of 6,453 individuals from 3,383 adult male and female same-sex and unlike-sex twin pairs from the Australian Twin Registry. The associations between the personality dimensions of positive emotionality, negative emotionality, and AD and CD risk were modest, whereas the associations between behavioral undercontrol and AD and CD risk were substantially higher. Genetic influences contributing to variation in behavioral undercontrol accounted for about 40% of the genetic variation in AD and CD risk and about 90% of the common genetic risk for AD and CD. These results suggest that genetic factors contributing to variation in dimensions of personality, particularly behavioral undercontrol, account for a substantial proportion of the genetic diathesis for AD and most of the common genetic diathesis for AD and CD among both men and women. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Human mu-opioid receptor variation and alcohol dependence

Mu-Opioid receptor-mediated neurotransmission is involved in the reward, tolerance, and withdrawal effects of alcohol. The present association study tested the hypothesis that the common Asn40Asp substitution polymorphism in the N-terminal domain of the human mu-opioid receptor (OPRM) confers vulnerability to subtypes of alcohol dependence. The genotypes of the Asn40Asp substitution polymorphism were assessed in 327 German alcohol-dependent subjects (according to ICD-10) and in 340 control subjects of German descent, using an assay based on allele-specific polymerase chain reaction. To select alcoholics with a presumed high genetic load, three subgroups were delineated, marked by (1) a family history of parental alcoholism (n = 114); (2) the inability to abstain from alcohol before the age of 26 years (n = 73); and (3) a history of alcohol withdrawal seizure or delirium (n = 107). The frequency of the Asp40 allele did not differ significantly between the controls [f(Asp40) = 0.078] and either the entire group of alcoholics [f(Asp40) = 0.107; p = 0.066], or the alcoholics with parental alcoholism [f(Asp40) = 0.114; p = 0.094], or the early-onset alcoholics [f(Asp40) = 0.096; p = 0.471,[ or the alcoholics with severe withdrawal symptoms [f(Asp40) = 0.098; p = 0.350]. Our results do not provide evidence that the common Asn40Asp substitution polymorphism of the OPRM gene contributes a major effect to the pathogenesis of alcohol dependence.     

Effect of alcohol on perceptual field dependence.

The stability of perceptual field dependence, as determined from rod-and-frame test (RFT) performance, when alcohol is ingested by nonalcoholic Ss was investigated. Ss randomly assigned to the experimental (Alcohol) and the control (No Alcohol) groups were found not to differ significantly on pretest RFT scores. A significant increase in perceptual field dependence occurred on the posttest for the Alcohol group, while the No Alcohol group showed no significant change. The difference between the change scores for the 2 groups was significant at p     

Prevalence of ICD-10 harmful use of alcohol and alcohol dependence among the rural population in Udmurtia

Aggressive treatment of thoracic malignancy may be complicated by complex defects in the chest wall. These may be associated with serious complications such as chronic infection, respiratory or cardiac failure, or major haemorrhage. Closure of the defect and restoration of the integrity of the chest wall is important for both functional and cosmetic reasons. Local flaps are often used, but may be inadequate or unavailable. Reconstruction with free flaps is better in these cases, as this provides as much abundant well-vascularised tissue as is required. We present 12 patients treated successfully for complex chest wall defects using various forms of local and free flap reconstruction. There were five complications, three healed spontaneously and two required secondary procedures before they healed.     

Prevalence of alcohol dependence and abuse in general practice

The aim of this study is to deliver representative epidemiological data about the prevalence of alcohol abuse and dependence in general practices in an urban area. In 12 general practices at Luebeck, a Northern German city with 220,000 inhabitants, a total of 929 patients (aged between 14 and 75 years) were screened using the CAGE and the Short Michigan Alcoholism Screening Test. If one of these screening questionnaires or the General Practitioners' assessment of the patient indicated an alcohol problem, the patient underwent a standardized diagnostic interview using the alcohol section of the Schedules for Clinical Assessment in Neuropsychiatry. The prevalence rates according to ICD-10 or DSM-III-R were 3.5% for alcohol abuse and 7.2% for alcohol dependence, the sex ratio was 1:2.8 (female:male). These results are compared with previous findings, and general epidemiological implications of this study are discussed.     

Naltrexone and alcohol dependence. Role of subject compliance

BACKGROUND: Two previous double-blind, placebo-controlled studies demonstrated that naltrexone (50 mg/d) reduces alcohol drinking in alcohol-dependent subjects. In both studies, treatment compliance was excellent. However, a robust treatment effect size for naltrexone relative to placebo has been shown for compliant subjects but not for subjects who missed research visits. The goal of this study was to determine the effectiveness of naltrexone in subjects who received psychosocial treatment in a more naturalistic setting with respect to the role of treatment attendance and medication compliance. METHODS: Ninety-seven alcohol-dependent subjects were randomly assigned to receive either naltrexone (n = 48) or matching placebo (n = 49) for 12 weeks. All subjects received individual counseling (twice per week for the first month followed by once per week). RESULTS: Overall, naltrexone showed only modest effects in reducing alcohol drinking for the 12 weeks of treatment. However, naltrexone treatment efficacy improved across a variety of outcome measures for subjects who completed treatment and were highly compliant with taking medication. CONCLUSIONS: Naltrexone is clinically effective relative to placebo in individuals who comply with the treatment protocol and take medication. The modest treatment effects in the entire sample suggest that the clinical efficacy of naltrexone could be improved by enhancing treatment compliance.     

ADH genotypes and alcohol use and dependence in Europeans

We have tested for effects of alcohol dehydrogenase (ADH) genotypes on self-reported alcohol consumption and symptoms of alcohol dependence, recorded on three occasions up to 15 years apart, in 377 male and female subjects of European descent. ADH2 genotype had significant effects on both consumption and dependence in the men, but not in the women. The effects of ADH3 genotype were considerably less than those of ADH2, but significant results could be demonstrated when the combined genotypes were considered. The direction of the effects on alcohol consumption and dependence risk were consistent with reports on Asian subjects, and with the in vitro properties of ADH isoenzymes. As with previous studies on the relationship between ADH type and alcohol use, population stratification cannot be excluded as a contributing factor in these results.     

Managing anxiety and depression in alcohol and drug dependence

Previous research has highlighted the high prevalence (30-60%) of comorbid anxiety and mood disorders in clients with substance misuse disorders and, equivalently, a third of those with affective disorder report a history of substance use disorder (Kessler et al., 1994; Regier et al., 1990; Robins & Regier, 1991). This article reviews the management of such cases and identifies key issues in the assessment process, as well as potential avenues for treatment. Other articles have highlighted the increased service utilisation and the cost of care and treatment of comorbidity. This article will primarily focus on the management of individual cases and will briefly refer to issues of service organisation. Although antidepressant or anxiolytic pharmacotherapy may have a role in the treatment of severe disorders, the benefits of using these medications must be balanced against the increased risk of side-effects or adverse reactions in individuals who continue to engage in substance misuse or who have medical complications associated with drug or alcohol dependency. Effective psychosocial approaches largely focus on brief, empirically tested manualised therapies such as cognitive therapy (Carroll, 1998a). However, modifications are required to such approaches to ensure that the interventions are tailored to the needs of clients exhibiting comorbidity. The data available demonstrate some evidence for the benefits of structured psychological approaches, but more sophisticated randomized controlled trials are required to evaluate the efficacy of both psychological and pharmacological approaches.     

Risk factors for alcohol dependence: a questionnaire survey

Several factors, known to associate with alcoholism, have not been studied together earlier as determinants of alcohol dependence, and taking into account possible interactions. A representative sample of 302 male and 312 female Finns, aged 19 to 81 years, answered a computerized questionnaire in January 1996. The diagnosis of alcohol dependence was based on the ICD-10 criteria. There were 66 (10.8%) subjects with current (past 12-month) ICD-10 alcohol dependence. After adjusting for other potential correlates in logistic regression analysis, alcohol dependence was more common among subjects high on both asocial behavior and on thinking that his or her behavior is determined mainly by chance or by other people (external control) than among the rest [odds ratio (OR) 4.4; 95% confidence interval (95% CI) 1.8-10.9]. Likewise, alcohol dependence was more common among subjects who recalled that they were highly stimulated when intoxicated by alcohol (OR 3.4; 95% CI 1.9-6.0). High predisposition to anxiety associated strongly with alcohol dependence among males (OR 13.8; 95% CI 4.4-43.1), but not among females (OR 2.5; 95% CI 0.7-9.1). Several of the aforementioned correlates may be modifiable risk factors for alcohol dependence.     

Effect of fetal alcohol exposure on adult symptoms of nicotine, alcohol, and drug dependence

The Tap (taxis toward peptides) receptor and the periplasmic dipeptide-binding protein (DBP) of Escherichia coli together mediate chemotactic responses to dipeptides. Tap is a low-abundance receptor. It is present in 5- to 10-fold-fewer copies than high-abundance receptors like Tar and Tsr. Cells expressing Tap as the sole receptor, even from a multicopy plasmid at 5- to 10-fold-overexpressed levels, do not generate sufficient clockwise (CW) signal to tumble and thus swim exclusively smoothly (run). To study the signaling properties of Tap in detail, we constructed reciprocal hybrids between Tap and Tar fused in the linker region between the periplasmic and cytoplasmic domains. The Tapr hybrid senses dipeptides and is a good CW-signal generator, whereas the Tarp hybrid senses aspartate but is a poor CW-signal generator. Thus, the poor CW signaling of Tap is a property of its cytoplasmic domain. Eighteen residues at the carboxyl terminus of high-abundance receptors, including the NWETF sequence that binds the CheR methylesterase, are missing in Tap. The Tart protein, created by removing these 18 residues from Tar, has diminished CW-signaling ability. The Tapl protein, made by adding the last 18 residues of Tar to the carboxyl terminus of Tap, also does not support CW flagellar rotation. However, Tart and Tapl cross-react well with antibody directed against the conserved cytoplasmic region of Tsr, whereas Tap does not cross-react with this antibody. Tap does cross-react, however, with antibody directed against the low-abundance chemoreceptor Trg. The hybrid, truncated, and extended receptors exhibit various levels of methylation. However, Tar and Tapl, which contain a consensus CheR-binding motif (NWETF) at their carboxyl termini, exhibit the highest basal levels of methylation, as expected. We conclude that no simple correlation exists between the abundance of a receptor, its methylation level, and its CW-signaling ability.