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Biomedical subjects

R F Anton

Publications and source records attributed to R F Anton.

At least 55 records · Page 3Linked to original sources

Carbohydrate-deficient transferrin as an indicator of drinking status during a treatment outcome study.

Biological markers of alcohol consumption have been used in both clinical and research settings to aid in the identification of relapse drinking. Although carbohydrate-deficient transferrin (CDT) has been shown to be a sensitive and specific marker for the identification of heavy drinkers, little data are available as to its utility as a marker for relapse drinking during treatment, particularly in comparison with the more widely used serum gamma-glutamyltransferase (GGT). CDT and GGT were measured in 35 male alcoholics before entering, and every 4 weeks during, a 12-week outpatient treatment trial combining pharmacotherapy and cognitive behavioral therapy. CDT and GGT were again measured 14 weeks after completion of treatment. During the 12-week treatment period, CDT showed a significant difference in those individuals who abstained from drinking (30% decrease), compared with those who relapsed (10% increase). GGT decreased on average in all individuals, and the change from treatment entry did not differ significantly across the drinking outcome groups. The change in CDT, but not GGT, from study entry to termination, significantly correlated with total alcohol consumption during the trial. At the 14-week posttreatment, follow-up evaluation CDT showed about a 60% elevation and GGT showed a 30% elevation, on average, from study entry values in those individuals who had relapse drinking by self and/or collateral report. The change in both markers differed between those individuals who remained abstinent or relapsed during the poststudy period. In general, the change in CDT from pretreatment levels seemed more sensitive to drinking status during treatment and follow-up than GGT. This indicates that CDT may be more sensitive marker for evaluating drinking status during both clinical and research treatment trials.

Adult↗

Neurobehavioural basis for the pharmacotherapy of alcoholism: current and future directions.

Results from studies of pharmacotherapies for primary alcoholism are reviewed, including selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors (e.g. fluoxetine), opiate antagonists (e.g. naltrexone) and dopamine agonists (e.g. bromocriptine). Because there is considerable comorbidity between alcohol dependence, anxiety, and affective disorders, results from studies of medications used to treat these psychiatric disorders are also reviewed, including the 5-HT agonist buspirone and the noradrenergic agent desipramine. The neurobehavioural model of alcohol dependence implies that combinations of medications may lead to more effective treatment; thus, identifying subtypes of alcoholic patients will be important in determining which therapies or combinations of therapy will be most effective in treating alcohol dependence. For example, in an ongoing study, we are attempting to subtype an alcoholic population for treatment selection by measuring endogenous opioid activity. Because endogenous opioids are involved in analgesia, we exposed male and female subjects with alcoholism [some of whom had post-traumatic stress disorder (PTSD)] to cold-induced pain and measured their response before and after administration of naloxone or placebo. The naloxone injection reduced pain response. In addition, women who have PTSD are much more sensitive to stress, which may be related to levels of brain opioid activity.

Adult↗

Neurobehavioural basis for the pharmacotherapy of alcoholism: current and future directions.

Results from studies of pharmacotherapies for primary alcoholism are reviewed, including selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors (e.g. fluoxetine), opiate antagonists (e.g. naltrexone) and dopamine agonists (e.g. bromocriptine). Because there is considerable co-morbidity between alcohol dependence, anxiety, and affective disorders, results from studies of medications used to treat these psychiatric disorders are also reviewed, including the 5-HT agonist buspirone and the noradrenergic agent desipramine. The neurobehavioural model of alcohol dependence implies that combinations of medications may lead to more effective treatment; thus, identifying subtypes of alcoholic patients will be important in determining which therapies or combinations of therapy will be most effective in treating alcohol dependence. For example, in an ongoing study, we are attempting to subtype an alcoholic population for treatment selection by measuring endogenous opioid activity. Because endogenous opioids are involved in analgesia, we exposed male and female subjects with alcoholism [some of whom had post-traumatic stress disorder (PTSD)] to cold-induced pain and measured their response before and after administration of naloxone or placebo. The naloxone injection reduced pain response. In addition, women who have PTSD are much more sensitive to stress, which may be related to levels of brain opioid activity.

Alcoholism↗

The Obsessive Compulsive Drinking Scale: a self-rated instrument for the quantification of thoughts about alcohol and drinking behavior.

It has been suggested that a crucial dimension of alcohol "craving" includes the concept of both obsessive thoughts about alcohol use and compulsive behaviors toward drinking. An interview-based rating scale, the Yale-Brown Obsessive Compulsive Scale-heavy drinkers (YBOCS-hd), has been found useful in quantifying this concept in alcohol-dependent individuals. A self-rating scale, the Obsessive Compulsive Drinking Scale (OCDS) has been developed by us as a modification of the YBOCS-hd. The YBOCS-hd showed excellent interrater reliability in our hands. The correlation between the YBOCS-hd and the OCDS total scores obtained on 60 alcohol-dependent individuals was 0.83. The test-retest correlation for the OCDS total score was 0.96, and the obsessive and compulsive subscales test-retest correlations were 0.94 and 0.86, respectively. The internal consistency of the items in the OCDS was high (0.86) and did not improve significantly with removal of individual items. The shared variance between the OCDS scores and alcohol consumption during the period of evaluation was only approximately 20%, indicating that the dimension measured by the scale was somewhat independent of actual drinking. As such, it might act as an independent measure of the "state of illness" for alcohol-dependent individuals. When used during a prospective 12-week treatment research study, initial results indicate that the OCDS seems to validly measure a dimension of alcohol dependence, because it decreased from baseline during alcohol reduction and increased in relationship to relapse drinking.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Carbohydrate-deficient transferrin levels in a female population.

Female college students (n = 49) from a small southwestern United States university participated in the 9-month study. Data collected included the assessment of drinking habits and other related substance use habits and serum levels of carbohydrate-deficient transferrin (CDT). Each subject provided an interview and blood sample on three occasions at 90-day intervals. Appended to the interview were a series of questions regarding stage of menstrual cycle and the diagnoses of certain diseases. The CDT values obtained were consistent with those obtained in other studies. Moderate-drinking subjects had significantly higher CDT values than did the abstainers and light drinkers. Females using oral contraceptives had significantly higher CDT values than those who were not taking oral contraceptives. Finally, although CDT values varied over time, they did not appear to vary as a function of menstrual cycle stage.

Adolescent↗

Neurobehavioral aspects of the pharmacotherapy of alcohol dependence.

A neurobehavioral basis for the pharmacologic treatment of alcoholism is beginning to emerge. Preclinical and clinical findings have provided valuable information on which to build bridges of understanding regarding the biological causes and treatment of alcoholism. Reinforcement and stress reduction are prominent in the initiation of alcohol use, while neuroadaptation to chronic alcohol exposure and Pavlovian conditioning of alcohol-like effects appear to be involved in the development of alcohol dependence. Impulsivity may play a crucial role in the rapidity with which alcohol dependence develops. This article presents a model that attempts to integrate these neurobehavioral phenomena with neurochemical systems. The pharmacological agents that have been studied for the treatment of alcoholism are reviewed in the context of this model. While medications that affect the serotonin system have been the most widely studied for the treatment of alcoholism, their clinical effects have been modest or inconsistent. Medications that affect dopaminergic neurotransmission have received less research attention, and their potential clinical utility may be limited by their side effect profile. The most efficacious agents for the treatment of alcoholism have been the opiate antagonists, including naltrexone. Naltrexone recently received approval from the U.S. Food and Drug Administration for relapse prevention in alcoholism. A number of recent clinical and animal studies suggest potential mechanisms of action for opiate antagonists in the treatment of alcoholism. Knowledge in this field is advancing rapidly. Developments in neurobiology, coupled with improvements in both animal models of alcohol self-administration and clinical trial methodology will surely further our understanding of the pathophysiology and pharmacotherapy of alcohol dependence.

Alcohol Drinking↗

Mood congruent and incongruent psychotic depressions: are they the same?

DSM-III and DSM-III-R instruct the clinician, if possible, to classify major depression with psychotic features into either the mood congruent (MC) or mood incongruent (MI) subtype. Patients hospitalized on a psychiatric unit for major depression with psychotic features were classified as predominantly MC or MI. The MC and MI groups did not differ significantly on a number of demographic or symptom severity variables. Thirteen (50%) MI patients experienced at least one MC symptom and 10 (71%) MC patients experienced at least one MI symptom. Overall, 25 (58%) of these patients experienced both MC and MI symptoms. This study demonstrates that subtyping psychotic depression into MC and MI subtypes is seldom an 'either-or' decision. Indeed, these results combined with findings from previous research suggests that there is no compelling scientific evidence for subclassifying psychotic depression into subtypes.

Adult↗

Implications of recent neuropsychopharmacologic research for understanding the etiology and development of alcoholism.

Recent studies in animals and humans have begun to provide insight into the neuropsychopharmacologic basis of alcohol consumption and dependence. Studies involving the serotonergic and opioidergic neurotransmitter systems have shown the most consistent results. Concurrent nosologic developments have led to the identification of subtypes of alcoholism on the basis of their clinical features and patterns of inheritance of alcoholism. These subtypes, which have implications for both the etiology and development of alcoholism, have also been linked theoretically to specific neurotransmitter systems. Consequently, the typologies both provide a hypothetical basis for selecting specific pharmacotherapies and have implications for molecular genetic investigation. This article selectively reviews the literature in these various areas in an effort to enhance understanding of the etiology and development of alcoholism.

Alcohol Drinking↗

Carbohydrate-deficient transferrin as a measure of immoderate drinking: remaining issues.

A growing body of investigations demonstrate that elevated levels of carbohydrate-deficient transferrin (CDT) effectively distinguishes alcoholics recently consuming large amounts of alcohol from light social drinkers or teetotalers. Nevertheless, important questions still remain concerning the value of CDT as a more generalized marker of alcohol consumption. Most important, the nature of the drinking pattern, including quantity and frequency, necessary to raise levels of CDT significantly remains unclear. Neither has research convincingly demonstrated that CDT is as accurate a marker for women, young adults, or non-Caucasian ethnic groups as for White, middle-aged men. Whereas CDT might serve as a useful outcome measure in trials of alcoholism treatment effectiveness, current research suggests that CDT is of limited value in identifying problematic drinking in general medical or community settings in which a broad continuum of drinkers is represented. Combining CDT with other biochemical or self-report screening measures may, however, improve sensitivity in these contexts. At present, the most accurate laboratory technique to detect CDT seems to be isoelectric focusing. Additional research, however, is needed to resolve the issue of whether CDT is best quantitated as a simple value or if its ratio to total transferrin or non-CDT results in higher predictive validity.

Alcoholism↗

A correlational study of carbohydrate-deficient transferrin values and alcohol consumption among Hispanic college students.

One hundred and forty-eight U.S. college students from a small southwestern university were asked to provide or complete the following: the Michigan Alcoholism Screening Test (MAST), a structured alcohol-use interview, and a 10-ml blood sample to be assayed for carbohydrate-deficient transferrin (CDT) levels and gamma-glutamyl-transpeptidase (GGTP) activity. Using the data obtained in the interview, only 2 females and 5 males were identified as heavy drinkers. Conclusions regarding the efficacy of the biochemical markers are therefore limited. It was found that CDT levels were significantly and positively correlated with various measures of alcohol consumption among males. There was no similar association between CDT, or GGTP, and alcohol consumption within the female sample.

Adolescent↗

Carbohydrate-deficient transferrin and gamma-glutamyltransferase as markers of heavy alcohol consumption: gender differences.

Carbohydrate-deficient transferrin (CDT) has been described as a more specific and sensitive marker of recent heavy alcohol consumption as compared with the current tests now available, such as gamma-glutamyltransferase (GGT). Most of the data generated from European populations have not compared the utility of CDT and GGT in the detection of heavy alcohol consumption as a function of gender. We examined the ability of both CDT and GGT to discriminate between 42 men and 18 women with heavy alcohol consumption (> 60 g/day) admitted to an alcohol detoxification center and a group of controls matched for age, race, and gender. CDT was higher, but GGT lower, in control females compared with males. Both CDT and GGT were higher in patients of both genders. At specificities > 90%, the sensitivity of CDT for detecting male alcohol abusers was 79% and for female alcohol abusers 44%. For GGT, the sensitivities were 65% and 44%, respectively. When both tests were used simultaneously, the sensitivity for the detection of alcohol abusers increased to 95% for males and 72% for females. Receiver Operator Characteristic analysis tended to confirm the superiority of CDT over GGT in the detection of heavy alcohol consumption in males, but not in females. A positive relationship was found between serum iron levels and CDT in control females but in no other group. The concordant findings of this American study with those in similar French and Finnish clinical populations, utilizing similar assay techniques, suggest that the measurement of CDT is clinically more useful than GGT in detecting recent heavy alcohol consumption in males.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Issues in the definition and measurement of drinking outcomes in alcoholism treatment research.

This article reviews methodological and conceptual issues regarding the choice of drinking outcome measures in alcoholism treatment research. The following issues are discussed: Should drinking outcomes be conceptualized in terms of an underlying unitary disorder, or should provision be made for independent outcomes that cover a wide variety of dimensions? Which drinking outcomes are typically measured in treatment evaluation studies and how are they operationalized? What are the empirical associations among drinking outcome measures? If multiple outcomes are measured, which should be given primary importance? Over what period of time should treatment outcome be evaluated? What procedures can be used to detect, correct or prevent the response bias associated with verbal report methods? Because outcome measures need to fit the hypotheses and practical needs of a particular study, it is unlikely that complete standardization can be achieved across all studies. Nevertheless, given the importance of drinking outcomes and the need for economy, two primary dependent measures are recommended: (1) proportion of available drinking days abstinent; and (2) intensity of drinking, as defined by the total amount consumed (in ounces absolute alcohol) during the follow-up period divided by the number of actual drinking days. This article also proposes a strategy that may help to guide the selection of outcome measures in future research.

Alcoholism↗

Multisite clinical trials in alcoholism treatment research: organizational, methodological and management issues.

Multisite clinical trials have two major advantages over single-site studies: the large sample size of multisite studies allows for adequate statistical power and better representativeness of the population being studied. However, they are more complex to implement than single-site studies. This article reviews previous multisite clinical trials of alcohol abuse and alcoholism, reasons for selecting a multisite design, management of such studies, and some statistical issues.

Alcoholism↗

Assessment issues and strategies in alcoholism treatment matching research.

Sensitive and comprehensive client assessment entails complex conceptual and methodological considerations. Such activity is at the heart of matching clients to appropriate treatments. This article begins by specifying the goals and functions of assessment to support matching. This is followed by a discussion of the strategies employed in Project MATCH to identify matching and outcome variables. The assessment battery used in Project MATCH is next described. Finally, an overview of issues surrounding administration of assessment measures is provided. Particular attention is given to the topics of sequencing and timing of measures.

Alcoholism↗

Response of psychotic depression subtypes to pharmacotherapy.

Patients with psychotic depression respond well when treated with a combination of an antidepressant and antipsychotic medication. We previously reported that they will respond in a similar fashion when treated with amoxapine monotherapy. There are few prospective studies on the pharmacologic treatment response of psychotic depression subtypes. We treated 37 inpatients, 21 with mood congruent (MC) psychotic depression and 16 with mood incongruent (MI) psychotic depression, in a randomized double-blind fashion with either the combination of amitriptyline and perphenazine or with amoxapine for 4 weeks. Depression and psychosis ratings improved in a similar manner in both the MC or MI patients irrespective of medication treatment group. Global response rates were similar in the MI patients and MC patients. The data suggest that classifying psychotic depression into MC versus MI subtypes may have limited acute prognostic value in pharmacotherapy response rates.

Adult↗

A placebo-controlled trial of buspirone in anxious inpatient alcoholics.

The present study is a double-blind control trial of buspirone versus placebo in highly anxious alcoholics who recently completed inpatient detoxification for alcoholism. Subjects met DSM-III-R criteria for generalized anxiety syndrome and/or other nonpanic forms of anxiety disorders and alcohol dependence. Male veterans aged 21 to 65 were randomized to 45 to 60 mg/day of buspirone (n = 33) or placebo (n = 34). Anxiety scores, as measured by the Hamilton Anxiety Scale and other anxiety measures, declined significantly for both groups, but there were no differential group differences throughout the 6-month treatment period. Survival analysis measuring time to study drop out, time to first drink, time to 5 consecutive drinking days, and time to first intoxication indicated no significant differences between groups. The number of standard drinks per drinking day for nonabstainers also did not differ between groups. In the present study anxious alcoholics taking buspirone did not receive any benefit over placebo on a number of anxiety and alcohol use measures.

Adult↗

Aspirin dose-dependently reduces alcohol-induced birth defects and prostaglandin E levels in mice.

The purpose of the present study was threefold. The first purpose was to determine if aspirin (ASA) decreases alcohol-induced birth defects in mice in a dose-dependent fashion. The second purpose was to see if the antagonism of alcohol-induced birth defects afforded by ASA pretreatment was related to dose-dependent decreases in prostaglandin E (PGE) levels in uterine/embryo tissue. The third purpose was to determine if ASA pretreatment altered maternal blood alcohol level. In experiments 1 and 2, pregnant C57BL/6J mice were administered ASA (0, 18.75, 37.5, 75, 150, or 300 mg/kg) on gestation day 10. One hour following the subcutaneous injection of ASA, mice received alcohol (5.8 g/kg) or an isocaloric sucrose solution intragastrically. In experiment 1 the incidence of birth defects was assessed in fetuses delivered by caesarean section on gestation day 19. In experiment 2 uterine/embryo tissue samples were collected on gestation day 10 1 hr following alcohol intubation for subsequent PGE analysis. In experiment 3 blood samples were taken at five time points following alcohol intubation from separate groups of alcohol-treated pregnant mice pretreated with 150 mg/kg ASA or vehicle. The results from the three experiments indicated that 1) ASA dose-dependently reduced the frequency of alcohol-induced birth defects in fetuses examined at gestation day 19, (2) ASA decreased the levels of PGE in gestation day 10 uterine/embryo tissue in a similar dose-dependent fashion, and 3) ASA pretreatment did not significantly influence maternal blood alcohol levels. These results provide additional support for the hypothesis that PGs may play an important role in mediating the teratogenic actions of alcohol.

Abnormalities, Drug-Induced↗