[Which prevention programs effectively reduce the risk of alcohol consumption in young people?]. / Quali programmi di prevenzione possono ridurre efficacemente il rischio di consumo di alcol nei giovani?

Alcohol consumption among young people is a major public health problem and the Italian National Health Institute considers it the leading cause of death for people under 24 years old, mainly due to road accidents. This study summarizes the evidence emerging from three Cochrane Collaboration reviews, aiming to orient the choice of alcohol prevention programs for young people. The first review considered schemes implemented at school to prevent alcohol consumption under 18 years of age; the second concerned studies on programs to reduce alcohol abuse by means of social norms; the third examined 56 trials on schemes for preventing young people from drinking. In the first review, 6 of 11 alcohol prevention schemes showed some signs of efficacy, and 14 of 39 schemes to combat substance abuse generally induced a significantly alcohol use reduction. The second review included three specific programs for alcohol-related problems with a > 17-month follow-up and they were effective. In the third review, 15 of 39 schemes proved effective in the short-term, 9 of 12 with medium follow-up were no longer effective (and alcohol consumption even increased in 2), while 3 long-term trials and 2 of 3 community schemes proved effective. These Cochrane reviews did not assess all strategies for preventing alcohol abuse in the young which have been implemented in different countries, because many interventions has been conducted spontaneously without any evaluation of their efficacy. An international registry on substance abuse prevention measures is warranted, with shared criteria for assessing their effects, to orient public health policies.

MRI in the assessment of muscular pathology: a comparison between limb-girdle muscular dystrophies, hyaline body myopathies and myotonic dystrophies.

PURPOSE: The continuous discovery of new subtypes of neuromuscular disorders demands more accurate imaging analyses. We set out to establish the specific patterns of muscular involution using magnetic resonance imaging (MRI). MATERIALS AND METHODS: A systematic clinical evaluation based on the Medical Research Council scale and MRI was completed in ten patients with calpainopathy [limb-girdle muscular dystrophy (LGMD)-2A], 16 with dysferlinopathy (LGMD-2B), ten with hyaline body myopathy (HBM), six with myotonic dystrophy (MD) types 1 and 5 with MD type 2. Severity of fibroadipose degeneration was specifically staged using T1-weighted sequences. Turbo inversion recovery magnitude (TIRM) sequences were used to assess oedema-like changes. RESULTS: T1 scans showed recurrent patterns of fibroadipose replacement, whereas TIRM images revealed differences in oedema-like changes between the various diseases. In LGMD, the posterior compartments are more vulnerable to degeneration. In HBM, fatty muscle degeneration and oedema are allocated to muscles of the posterior compartments of the leg. In MD, fatty muscle degeneration and oedematous changes are allocated to muscles of the anterior thigh and posterior lower leg. CONCLUSIONS: Imaging examination suggests a characteristic pattern of muscle involvement. MRI represents an important diagnostic technique useful in differential diagnosis, thanks to the distinctive patterns observed in the distribution of muscular changes between the different muscular diseases.

Alcohol- and substance-dependent subjects: the correlated factors in qualifying for liver transplantation.

OBJECTIVES: To identify the most significant variables in determining if candidates with past or current addictions can be considered for liver transplantation. METHODS: Data relating to 58 cases from January 2001 to December 2003 were collected and analyzed. RESULTS: The decisional algorithm identified by discriminant analysis is based on the following variables: the duration of remission, treatment adherence, and the presence of a valid help relationship. Candidates undergoing initial remission (up to 12 months) must demonstrate both adherence and affective support; those with over 5 years of remission, however, are considered sufficiently reliable. A positive judgment is significantly correlated to overall survival and clinical improvement even without transplantation. CONCLUSIONS: In toxicological evaluation, treatment adherence and the presence of a valid help relationship for patients in remission from addictions can improve the selection criteria for liver transplantation, making it more dependable.

Gamma-hydroxybutyric acid in the treatment of alcohol and heroin dependence.

We briefly review two double-blind, placebo-controlled surveys conducted in this laboratory with the aim of evaluating the efficacy of gamma-hydroxybutyric acid in the treatment of alcohol withdrawal syndrome as well as alcohol craving and consumption in alcoholics. In the first study, acute administration of 50 mg/kg gamma-hydroxybutyric acid, a nonhypnotic dose in alcoholic patients, resulted in a rapid and significant reduction of the severity score of alcohol withdrawal signs and symptoms that lasted as long as 7 hours. In the second study, treatment with 50 mg/kg/day gamma-hydroxybutyric acid for 3 consecutive months (1) reduced the number of daily drinks by approximately 50%, (2) increased the days of abstinence approximately threefold, and (3) reduced the alcohol craving score by up to 60%. These results feature gamma-hydroxybutyric acid as an effective agent for the treatment of alcohol dependence. Data on the effect of gamma-hydroxybutyric acid on opiate withdrawal syndrome also are reviewed. Administration of 25 mg/kg induced a marked reduction of opiate withdrawal score in both heroin- and methadone-dependent subjects. Finally, we report the cases of adverse reactions to and abuse of gamma-hydroxybutyric acid revealed in a retrospective analysis of patients recruited in this laboratory over a 10-year period.

Clinical efficacy of gamma-hydroxybutyric acid in treatment of opiate withdrawal.

This paper describes the role of gamma-hydroxybutyric acid (GHB) in the treatment of opiate withdrawal syndrome. In the two patients described, after having abruptly withdrawn from long-term methadone treatment, GHB was orally administered (each dose given every 4-6 h) for 8-9 days. The GHB showed both a high efficacy (some mild and transient symptoms attributable to opiate withdrawal were observed, but only in the first days of therapy) and a good tolerability (no clinical phenomena interpreted as GHB side effects were found). These results could be of interest in improving the pharmacological treatment of drug addiction.

Gamma-hydroxybutyric acid for treatment of opiate withdrawal syndrome.

In a double-blind placebo-controlled trial, gamma-hydroxybutyric acid (GHB) (25 mg/kg orally) suppressed most of the withdrawal symptomatology in 14 heroin addicts and 13 methadone-maintained subjects. The GHB effect was prompt (within 15 minutes) and persisted for between 2 and 3 hours. Subsequently, the same patients received GHB in an open study every 2 to 4 hours for the first 2 days and 4 to 6 hours for the following 6 days: most abstinence signs and symptoms remained suppressed and patients reported felling well. Urine analysis failed to detect any presence of opiate metabolites. No withdrawal symptomatology recurred after 8 days of treatment when GHB was suspended, and patients were challenged with an intravenous injection of 0.4 mg naloxone. The results indicate that GHB may be useful in the management of opiate withdrawal.

Therapeutic gamma-hydroxybutyric acid monitoring in plasma and urine by gas chromatography-mass spectrometry.

A gas chromatographic-mass spectrometric (GC-MS) method for the determination of therapeutic levels of gamma-hydroxybutyric acid (GHB) in plasma and urine samples is described. GHB is converted to its lactonic form gamma-butyrolactone (GBL) which is extracted from biological fluids after the addition of the internal standard delta-valerolactone. Final GC-MS analysis is obtained under electron impact selected ion monitoring (SIM) conditions. Mean relative recoveries of GHB from plasma and urine are 75.5% (RSD% = 2.2) and 76.4% (RSD% = 2.4), respectively. The assay is linear over a plasma GHB range of 2-200 micrograms ml-1 (r = 0.999) and a urine GHB range of 2-150 micrograms ml-1 (r = 0.998). Intra- and inter-assay relative standard deviations (n = 5) determined at 10 and 100 micrograms ml-1 are below 5%. The method is simple, specific and accurate, and may be applied for analytical purposes related to pharmacokinetic studies and therapeutic drug monitoring.

Dose-dependent absorption and elimination of gamma-hydroxybutyric acid in healthy volunteers.

Gamma-hydroxybutyric acid (GHB) is effective in treatment of the alcohol and opiate withdrawal syndromes. Its absorption and disposition kinetics have been studied in 8 healthy male volunteers following oral administration of single doses of 12.5, 25 and 50 mg kg-1. The AUC increased disproportionately with the dose and so the apparent oral clearance decreased significantly as the dose was increased, whereas the terminal half-life and mean residence time increased. The peak plasma concentrations normalised to the lowest dose fell significantly with increasing doses, whilst the corresponding peak times increased. These findings suggest that both the oral absorption and the elimination of GHB are capacity-limited processes. GHB did not bind to significant extent to plasma proteins over the therapeutic concentration range. The pharmacokinetic parameters in healthy volunteers were not significantly different from those previously observed in alcohol-dependent patients with compensated alcoholic liver disease.

Pharmacokinetics of gamma-hydroxybutyric acid in alcohol dependent patients after single and repeated oral doses.

1. The pharmacokinetics of gamma-hydroxybutyric acid (GHB) were studied in 10 alcohol dependent subjects after single and repeated therapeutic oral doses (25 mg kg-1 every 12 h for 7 days). 2. GHB was readily absorbed and rapidly eliminated (tmax = 20-45 min; mean t1/2z 27 +/- 5 s.d. min). Urinary recovery of unchanged GHB was negligible (less than 1% of the dose). gamma-butyrolactone was not detected in either plasma or urine, indicating that lactonization of GHB does not occur in vivo. 3. The multiple-dose regimen resulted neither in accumulation of GHB nor in time-dependent modification of its pharmacokinetics. 4. In five subjects, the data were consistent with nonlinear elimination kinetics of GHB. Administration of a 50 mg kg-1 dose to these subjects resulted in significant increases in dose-normalized AUC, t1/2z and mean residence time. 5. Doubling of the dose also resulted in a significant increase in tmax with little change in Cmax. 6. At the administered doses, GHB did not accumulate in the plasma and caused no serious side effects.

gamma-Hydroxybutyric acid in the treatment of alcohol dependence: a double-blind study.

The effect of gamma-hydroxybutyric acid on alcohol consumption and alcohol craving in alcoholics was investigated in a randomized double-blind study versus placebo. Patients were treated as outpatients during a three month period either with gamma-hydroxybutyric acid (50 mg/kg/day, divided into three daily doses) or with placebo. Of the 82 alcoholics that entered the study, 71 completed it, 36 in the gamma-hydroxybutyric acid and 35 in the placebo group. Alcohol consumption was assessed by the subject's self report. At the 3rd month of treatment, 11 patients in the gamma-hydroxybutyric acid group referred to be abstinent and 15 referred controlled drinking; while in the placebo group only two and six patients referred abstinence and controlled drinking, respectively. Serum-gammaglutamyl-transferase activity correlated with the admitted alcohol consumption. Gamma-hydroxybutyric acid treatment decreased alcohol craving during the 3 months of treatment. Transient side effects were noted by six patients on gamma-hydroxybutyric acid and two on placebo. The results suggest that gamma-hydroxybutyric acid may be useful in the treatment of alcohol dependence.

Pain symptoms in an adolescent Italian population.

We have assessed the incidence of four types of self-reported pain symptoms (headache, pain in heart or chest, pain in lower back and muscle soreness) in a randomised sample of 1413 persons from a population of 93481 students aged 14-16 years in the Veneto region of Italy. In males, 26% reported moderate and 1.2% severe pain distress. In female, 35% and 3.7% reported moderate and severe pain respectively. Pain symptoms were positively correlated with anxiety and depressive symptoms and were more frequent in females.

Gamma-hydroxybutyric acid for treatment of alcohol withdrawal syndrome.

The effect of gamma-hydroxybutyric acid (GHB) on ethanol withdrawal syndrome in alcoholics was investigated in a randomised double-blind study. Patients with withdrawal symptoms were treated either with GHB (orally in a syrup preparation) (11 patients) or with the syrup alone (12). GHB treatment (50 mg/kg) led to a prompt reduction in withdrawal symptoms, such as tremors, sweating, nausea, depression, anxiety, and restlessness. The only side-effect was dizziness. GHB may be useful in the management of alcohol withdrawal syndrome in man.

[Naltrexone and prevention of opiate dependence relapse. An Italian experience]. / Naltrexone e prevenzione della recaduta nella dipendenza da oppiacei. Una esperienza italiana.

A group of 93 patients consecutively treated for Opiate Dependence (DSM) III) was examined and the relationship between detoxification outcome and treatment with an opiate antagonist (naltrexone), sociodemographic characteristics and clinical features was studied. The treatment with naltrexone followed detoxification in 46 cases (50%). Average retention is 16.7 weeks, much longer than reported in the literature. This outcome is ascribed to: 1) better social adjustment of the population considered, in terms of employment, relatives' involvement in the treatment and Opiate Dependence in partners; 2) introduction of naltrexone in a multimodal program, including psychological and social support.

Locus of control, life events and treatment outcome in alcohol dependent patients.

We investigated the relationship of locus of control and life events to outcome of treatment at 6 months in 67 patients with alcohol dependence. Outcome was less favourable in patients with pre-treatment scores indicating external locus of control than in those with internal locus of control. Furthermore, patients with relapse in the follow-up period experienced more independent life events with moderate to severe objective negative impact than those with more favourable outcome. These results suggest that locus of control may be of clinical use in formulating treatment and prognosis, and that the occurrence of life events may influence outcome. The results are discussed in relation to strategies for treatment and prevention of relapse.

Alcohol intake and withdrawal: effects on branched chain amino acids and alanine.

The effects of chronic alcohol consumption on plasma branched chain amino acids and alanine concentrations were evaluated, and basal blood concentrations of these amino acids were determined after chronic ethanol intake and following a withdrawal period in 30 admitted alcoholics. After ethanol intake, alcoholics showed increased branched chain amino acid concentrations; the blood alanine concentrations were depressed after the withdrawal period. To evaluate the effect of ethanol on diurnal variations of these amino acids in the blood, a group of these patients underwent two isocaloric diets with and without wine. The diet with alcohol induced a sustained increase of branched chain amino acids persisting even after the postprandial phase with a decrease of alanine as compared to the diet without.