Targeted naltrexone treatment of early problem drinkers.

Naltrexone is approved for daily use in the treatment of alcohol dependence. We evaluated the feasibility of using targeted naltrexone (i.e., on an "as-needed" basis) to treat early problem drinkers. Twenty-one subjects (52% male) received brief coping skills training weekly for 4 weeks, along with naltrexone (50 mg), which they were instructed to use 2 to 5 times per week in anticipation of high-risk drinking situations. During treatment, statistically and clinically significant declines were observed across a variety of drinking-related outcomes, including the intensity of drinking, the decline in which was correlated with medication use. Beneficial effects of the intervention were still evident during the 3-month posttreatment period. Further research, including a placebo-controlled evaluation of targeted naltrexone, is needed to determine the optimal treatment strategy for early problem drinkers, many of whom are seen in the primary-care medical setting.

Measuring intracavity phase changes by use of double pulses in a linear cavity.

We report the use of a mode-locked linear-cavity Ti:sapphire laser as a sensitive phasemeter. We were able to generate two pulses in the cavity by placing an absorbing-dye jet in the middle of the cavity. A voltage applied to an intracavity LiNbO(3) crystal modified the phase velocity for one of the two pulses at each of its passes. We could then measure accurately the change in optical cavity length by observing a beat frequency between the two pulses. We measured the ratio of the r(33) to r(13) electro-optic coefficients in LiNbO(3) to be 3.57+/-0.1 , in close agreement with the accepted value of 3.62.

Ritanserin in the treatment of alcohol dependence--a multi-center clinical trial. Ritanserin Study Group.

Four hundred and twenty-three alcohol dependent subjects were enrolled into a 12-week randomized, double-blind, placebo-controlled study to determine the safety and efficacy of the 5-HT2 receptor antagonist, ritanserin (2.5 mg/day or 5 mg/day), in reducing alcohol intake and craving. All subjects received 1 week of single-blind placebo prior to randomization into the 11-week double-blind phase. Additionally, all subjects received weekly individual sessions of manual-guided cognitive-behavioral therapy. Comparing the single-blind period with endpoint, there was approximately a 23% reduction in drinks/day; 34% fall in the total number of drinking days/week; 22% decrease in drinks/drinking day; and a 37% diminution in alcohol craving for all treatment groups. All treatment groups experienced a beneficial clinical outcome as assessed by the Clinical Global Impression Scale. There was, however, no significant difference between treatment groups on any of these measures of alcohol drinking, craving, or clinical outcome. Subjects were of relatively high social functioning at baseline, and this did not change significantly during treatment. Treatment groups did not differ significantly on either medication compliance or reported adverse events. Ritanserin treatment was associated with a dose-related prolongation of subjects' QTc interval recording on the electrocardiogram. These results suggest that alcohol dependent subjects can show marked clinical improvement within a structured alcohol treatment program. These findings do not support an important role for ritanserin in the treatment of alcohol dependence.

Psychometric properties and validity of the obsessive-compulsive drinking scale.

Abstinent alcoholics' self-reports of distressing alcohol-associated thoughts and compulsions to drink were evaluated by the Obsessive-Compulsive Drinking Scale (OCDS). Exploratory and confirmatory factor analyses on separate subject samples revealed that subjects' OCDS responses were best described by four correlated dimensions: alcohol obsessions, alcohol consumption, automaticity, and interference due to drinking. The validity of this four-factor solution was supported by the pattern of associations with drinking and coping style measures. In particular, alcohol obsessions were positively associated with alcohol dependence and use of passive/ avoidant coping. Automaticity was positively associated with the intensity and salience of drinking, and inversely associated with use of active/approach coping, as well as abstinence duration. The obsession and automaticity subscales of the OCDS may be useful in evaluating cognitive-motivational processes associated with recovery from alcoholism.

The Alcohol Use Disorders Identification Test (AUDIT): validation of a screening instrument for use in medical settings.

OBJECTIVE: The concurrent, construct, and discriminant validity of the Alcohol Use Disorders Identification Test (AUDIT) were evaluated. AUDIT consists of a 10-item Core questionnaire and an 8-item Clinical procedure. AUDIT was designed to identify hazardous drinkers (whose drinking increases their risk of alcohol-related problems, though alcohol-associated harm has not yet occurred); harmful drinkers (who have had recent physical or mental harm from their drinking, but who are not alcohol-dependent); and people with alcohol dependence. METHOD: Known alcoholics (n = 65) and general medical patients (n = 187) completed self-report questionnaires and underwent a diagnostic interview, physical examination and laboratory testing. RESULTS: AUDIT scores correlated significantly with scores on the MAST and MacAndrew alcoholism screening tests, and with ALAT, ASAT, GGT and MCV levels, which reflect recent heavy drinking. AUDIT scores were correlated with measures of alcoholism vulnerability (e.g., familial alcoholism and sociopathy), and with somatic and affective consequences of drinking. Receiver operating characteristic and discriminant function analyses indicated that the AUDIT Core and Clinical Instruments were sensitive and specific in discriminating alcoholics from medical patients, most of whom were nonalcoholics. The AUDIT Core was superior to the MAST and the AUDIT Clinical in discriminating hazardous drinkers from nonhazardous drinkers. It was also superior to the AUDIT Clinical in discriminating harmful from nonharmful drinkers. CONCLUSIONS: The AUDIT Core Instrument is useful for early detection of hazardous or harmful drinking, while the AUDIT Clinical Instrument is better applied to identification and/or confirmation of cases of alcohol dependence.

Development and initial validation of a measure of drinking urges in abstinent alcoholics.

Although drinking urges and cravings are commonly reported by alcoholics, prospective studies have found inconsistent associations between such urges and drinking relapses. Previous studies have measured drinking urges by use of single-item ratings of alcohol craving or other measures of unknown reliability and validity. To permit improved evaluation of hypotheses regarding alcohol craving, a 49-item questionnaire that reflects several urge-related domains was developed and pretested. Items assessed subjects' desire for a drink, expectations of positive effects following drinking, relief of withdrawal and negative affect following drinking, and intention to drink. Exploratory and confirmatory factor analyses of the responses of 351 abstinent, treatment-seeking alcoholics indicated that alcohol urges are best described by a single factor. Based on these analyses, an internally consistent, reliable, and psychometrically valid 8-item scale, the Alcohol Urge Questionnaire (AUQ), was developed. Data indicated that AUQ scores were strongly related to alcohol dependence severity and to cognitive preoccupation with alcohol, and that they declined with prolonged abstinence. The AUQ may be useful in alcoholism treatment research and in laboratory studies of reactivity to alcohol or other manipulations.

Placebo-controlled trial of fluoxetine as an adjunct to relapse prevention in alcoholics.

OBJECTIVE: The authors tested the hypothesis that fluoxetine, when used in combination with relapse prevention psychotherapy, directly reduces relapse frequency and severity for alcoholics. METHOD: The authors conducted a randomized, placebo-controlled trial of fluoxetine (up to a maximum of 60 mg/day) for 12 weeks in combination with weekly psychotherapy for 101 alcohol-dependent subjects who were not selected on the basis of comorbid major depression. Outcomes were measured at the end of treatment and 6 months after treatment. RESULTS: Placebo-treated subjects were more complaint with the medication regimen and remained in the study longer than fluoxetine-treated subjects. There was significantly less alcohol consumption in both groups during treatment than before treatment. These effects persisted during the posttreatment period. Although fluoxetine treatment had no significant effects on alcohol consumption, it reduced Hamilton Depression Rating Scale scores more than placebo treatment among subjects with current major depression. CONCLUSIONS: Fluoxetine at a dose of 60 mg/day is probably not of use for relapse prevention in alcoholics with mild to moderate alcohol dependence and no comorbid depression. In alcoholics with major depression, the drug may reduce depressive symptoms. Subsequent studies with fluoxetine should probably focus on more severely alcohol-dependent subjects or those with comorbid depression.

Buspirone treatment of anxious alcoholics. A placebo-controlled trial.

BACKGROUND: Symptoms of anxiety are common in alcoholics and may contribute to relapse following initiation of abstinence. Buspirone hydrochloride, a serotonin1A partial agonist, has a pharmacologic profile that may be particularly suited to the treatment of anxious alcoholics. METHODS: We conducted a randomized, 12-week, placebo-controlled trial of buspirone in 61 anxious alcoholics, all of whom also received weekly relapse prevention psychotherapy. Outcomes were measured at the end of treatment and at a 6-month follow-up evaluation. RESULTS: Buspirone therapy was associated with greater retention in the 12-week treatment trial, reduced anxiety, a slower return to heavy alcohol consumption, and fewer drinking days during the follow-up period. CONCLUSIONS: Buspirone appears to have a useful role in the treatment of anxious alcoholics. Further research is needed to clarify which patient characteristics and concomitant treatments result in optimal response to buspirone therapy.

Alcoholism.

Several medications may help improve treatment of alcoholic patients. Medications that effectively and specifically reverse symptoms of alcohol intoxication or coma currently are lacking. Benzodiazepines remain the most effective medications for the treatment of alcohol withdrawal and for the prevention of withdrawal seizures and delirium, even though the adrenergic agents clonidine or atenolol may hasten resolution of withdrawal symptoms and facilitate outpatient detoxification. Psychosocial rehabilitation of alcoholics may be improved by judicious addition of the alcohol-sensitizing agents disulfiram and carbimide, the serotonergic drugs fluoxetine and buspirone, the opiate antagonist naltrexone, and, for primarily depressed alcoholics, tricyclic antidepressants. As in psychosocial alcohol rehabilitation, patient-treatment matching may improve results of pharmacotherapeutic intervention.

Comparative study of cefazolin, cefamandole, and vancomycin for surgical prophylaxis in cardiac and vascular operations. A double-blind randomized trial.

Three-hundred twenty-one adults undergoing cardiac or major vascular operations were randomized to receive intravenous cefazolin, cefamandole, or vancomycin for prophylaxis against surgical infection in a double-blind trial. All three regimens provided therapeutic blood levels throughout operation in patients studied undergoing cardiopulmonary bypass. The prevalence of surgical wound infection was lowest with vancomycin (4 infections [3.7%] versus 14 [12.3%] and 13 [11.5%] in the cefazolin and cefamandole groups, respectively; p = 0.05); there were no thoracic wound infections in cardiac operations in the vancomycin group (p = 0.04). The mean duration of postoperative hospitalization was lowest in the vancomycin group (10.1 days; p < 0.01) and highest in the cefazolin group (12.9 days). Prophylaxis with vancomycin or cefamandole, compared with cefazolin, did not prevent nosocomial cutaneous colonization by methicillin-resistant coagulase-negative staphylococci; colonization or infection with vancomycin-resistant staphylococci or enterococci was not detected. Adverse effects attributable to the prophylactic regimen were infrequent in all three groups. Eight patients given vancomycin became hypotensive during administration of a dose, despite infusion during a 1-hour period; however, slowing the rate of administration and pretreating with diphenhydramine allowed vancomycin to be resumed and prophylaxis completed uneventfully in five of the patients. We conclude that administration of vancomycin (approximately 15 mg/kg), immediately preoperatively, provides therapeutic blood levels for surgical prophylaxis throughout most cardiac and vascular operations, resulting in protection against postoperative infection superior to that obtained with cefazolin or cefamandole. Vancomycin deserves consideration for inclusion in the prophylactic regimen (1) for prosthetic valve replacement and prosthetic vascular graft implantation, to reduce the risk of implant infection by methicillin-resistant coagulase-negative staphylococci and enterococci; (2) for any cardiovascular operation if the patient has recently received broad-spectrum antimicrobial therapy; and (3) for all cardiovascular operations in centers with a high prevalence of surgical infection with methicillin-resistant staphylococci or enterococci. Guidelines for dosing and administration of vancomycin for cardiovascular surgical prophylaxis are provided.

A hospital discharge code review of toxic shock syndrome in Wisconsin.

The Wisconsin Division of Health conducted a review of discharge coding for 142 (97%) of the state's general care hospitals for the period 1980-1983 to evaluate the use of International Classification of Diseases codes for toxic shock syndrome and to estimate completeness of reporting of recognized hospitalized cases of the syndrome to the Division of Health. Hospital use of code 040.89 (other bacterial diseases-other) recommended for toxic shock syndrome by the National Center for Health Statistics in January 1981 increased from 23% of Wisconsin hospitals in 1980 to 92% in 1983. The sensitivity of this code for toxic shock syndrome increased from 54% to 85% from 1981 to 1983; study population specificity was stable at approximately 95%, and the predictive value was 65% in 1981 and 70% in 1983. The use of codes 785.50 (shock, unspecified) and 785.59 (nontraumatic shock-other) frequently assigned to toxic shock syndrome was also assessed; all measures of their utility decreased in proportion to the increasing use of 040.89. The coding review identified 20 previously unreported cases of toxic shock syndrome; the 10 confirmed and 10 probable cases represent 4% and 21% of the state's 223 confirmed and 47 probable cases with onsets in 1980-1983. Results indicate that a National Center for Health Statistics coding recommendation for a disease of emerging significance can result in relatively uniform coding of the illness, which can provide a tool for case finding and surveillance evaluation for hospitalized cases.

SV40 viral minichromosome: preferential exposure of the origin of replication as probed by restriction endonucleases.

Isolated SV40 minichromosomes [1-3] were treated with different single-cut restriction endonucleases to probe the arrangement of nucleosomes in relation to the SV70 DNA sequence. While Eco RI and Bam HI each cut 22-27% of the SV40 minichromosomes under limit-digest conditions, Bgl I, which cuts SV40 DNA at or very near the origin of replication [4,5], cleaves 90-95% of the minichromosomes in a preparation. Similar results were obtained with minichromosomes which had been fixed with formaldehyde before endonuclease treatment. One possible interpretation of these findings is that the arrangement of nucleosomes in the compact SV40 minichromosomes is nonrandom at least with regard to sequences near the origin of DNA replication.