Alcohol and Alcoholism

Published by Oxford University Press (OUP)
Online ISSN: 1464-3502
Publications
Proportion of fatal accidents involving alcohol using the FARS imputed BAC (Texas, January 1995-September 2002). 
Time-series (ARIMA) models of FARS data for fatal accidents a 
Time-series (ARIMA) models of DPS data for all accidents using proxy measure of alcohol use by driver a 
Article
The purpose of the present study was to assess the effects on alcohol-involved traffic crashes and fatalities of the 0.08 blood alcohol concentration (BAC) per se law introduced in the state of Texas in 1999. Data pertaining to alcohol-involved traffic crashes and fatalities were extracted from two datasets: the Fatality Analysis Reporting System (FARS) compiled by the National Highway Traffic Safety Administration (for the period January 1995-September 2002), and the Texas Department of Public Safety (DPS) reports of Alcohol Related Motor Vehicle Traffic Accidents and Casualties (for the period January 1995-December 2000). The data were analysed using time-series methods (ARIMA routines). The effects of the law on all drivers were assessed, along with the effects among gender, racial, and age subgroups and crash location (urban vs rural). Separate time-series analyses were conducted with all alcohol-involved and fatal alcohol-involved crashes from the DPS dataset and fatal alcohol-involved crashes from the FARS dataset as the outcome variables. None of the effects for either the total sample or any of the subgroups analysed was statistically significant (this was true of both the FARS and DPS datasets). While there is a growing body of evidence that indicates that 0.08 BAC laws can be effective in reducing alcohol-involved traffic accidents and fatalities, the present study shows that this was not the case in Texas. Future research should move beyond the simple question of whether or not 0.08 BAC laws 'work' and instead explore in more detail the conditions, such as publicity and enforcement, under which the law does or does not contribute to a decline in alcohol-involved accidents and fatalities.
 
Article
Low amounts of 1,2-dibromoethane (DBE), not able per se to exert pro-oxidant and cytotoxic activity on rat hepatocyte suspensions, become effective when administered with carbon tetrachloride (CCl4), due to impairment of the glutathione transferase detoxication pathway by CCl4. Treatment of rats with a single dose of ethanol (2.5 g/kg body wt) 2 h before liver cell isolation potentiates the effect of DBE alone on both malonaldehyde formation and lactate dehydrogenase release by the hepatocyte. The potentiation of the DBE effects by ethanol may be through a series of mechanisms, such as a strong inactivation of hepatocyte glutathione transferase similar to that caused by CCl4, an increased basal level of lipid peroxidation and a significant loss of total glutathione.
 
Article
Previous experiments with hepatocytes isolated from ethanol-treated rats showed that alcohol potentiates the toxic action of 1,2-dibromoethane (DBE) by inhibiting its metabolism via glutathione-S-transferase. The aim of this study was to investigate whether acetaldehyde, the main product of ethanol metabolism, may be responsible for such inactivation. By pretreatment with 4-methylpyrazole, an inhibitor of acetaldehyde formation, the ethanol inactivation of glutathione transferase was actually prevented. As a consequence of this protective action, 4-methylpyrazole also prevented the high basal lipid peroxidation and the potentiated DBE toxicity observed in hepatocytes from ethanol-dosed animals. Finally, the inactivation of glutathione-S-transferase by concentrations of acetaldehyde likely to occur in the ethanol-intoxicated animal was confirmed in an in vitro model by direct aldehyde addition to hepatocyte suspensions.
 
Radioactive phospholipid incorporation into rat cerebellar membranes 
Article
In this study, we have analysed the effect of ethanol and phosphatidylethanol, a unique phospholipid formed only in the presence of ethanol, on the binding of [3H]inositol 1,4,5-trisphosphate to rat cerebellar membranes. Rats were intraperitoneally injected daily with 3 g of ethanol/kg body weight for different periods of time. Repeated administration of ethanol induced a reduction in the binding capacity (Bmax) without affecting the affinity constant (Kd). A significant 32% reduction was observed after 21 days of exposure (from control Bmax values of 25 +/- 3 pmol/mg and Kd values of 9 +/- 2 nM). In an in-vitro assay, phosphatidylethanol (500 microM) and phosphatidic acid (500 microM, but no other phospholipids tested, induced a reduction in Bmax (39% and 43%, respectively). The observed effect displayed by phosphatidylethanol was not due to its degradation to phosphatidic acid or other phospholipids. The results emphasize the importance of examining phosphatidylethanol (PEth) as a possible mediator of the effects of ethanol on cellular processes. However, the role of PEth in the observed effect of long-term ethanol exposure still needs further consideration.
 
Article
Chronic alcohol intake produces an increase in the concentration of glucose 1,6-bisphosphate and fructose 2,6-bisphosphate in human muscle before the first sign of myopathy appears. When myopathy was present both sugars decreased to the levels of healthy humans. These changes could contribute to the decline in skeletal muscle performance.
 
Article
A computer-assisted and cross-reference literature search identified trials of therapy for alcohol withdrawal symptoms. Those with a randomized, double-blind placebo-controlled design were systematically assessed for quality of methodology. Fourteen studies were identified investigating 12 different drugs. The quality of methodological design, even among this highly selected group of published studies, was often poor. Study populations were generally under-defined, most studies excluded severely ill patients, control groups were poorly matched, and the use of additional medication may have confounded results in some studies. Twelve different rating scales were used to assess severity of symptoms. All 12 compounds investigated were reported to be superior to placebo, but this has only been replicated for benzodiazepines and chlormethiazole. Further research using better methods is required to allow comparison of different drugs in the treatment of alcohol withdrawal symptoms. On the evidence available, a long-acting benzodiazepine should be the drug of first choice.
 
Article
Plasma-HDL-cholesterol levels were determined in 104 patients (92 males and 12 females) with a mean age of 43 years (range 20–70 years). All were admitted to a clinic for alcoholics and had a mean drinking history of 13 years with a mean consumption of 48.2 1 of pure ethanol per year. There was no correlation between HDL-cholesterol level and the total ethanol consumption in the year before admission or in the month before admission. However, weak negative correlations between HDL-cholesterol and smoking habits (r=−0.26, P± 0.001) and body weight (r=−0.34, P± 0.001) were found. In 40 patients the mean HDL-cholesterol level decreased from 1.94 ± 0.75 mmol/l (SD) at admission to 1.29 f 0.36 mmol/l after 16 days of abstinence. Altogether, 33 (31.6%) of 104 patients had a HDL-cholesterol level above our reference value of 2 mmol/l while alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT) and gamma-glutamyltranspeptidase (GGT) were increased in 49, 52.9 and 70.3%, of the cases respectively. Although screening programmes have shown an association between plasma-HDL-cholesterol and the number of drinks consumed per day, no such association could be found in a sample of alcoholics. Decrease of HDL-cholesterol during abstinence, however, seems to be a marker in alcoholics.
 
Article
The effect of the selective 5-HT3 receptor antagonist MDL 72222 on voluntary ethanol consumption was examined in Sardinian ethanol-preferring (SP) rats in a free choice (10% ethanol and water) experiment. SP rats consumed 8.1 +/- 1.1 g/kg ethanol daily. MDL 72222 treatment (3.0, 5.0 and 7.0 mg/kg i.p. 3 times daily for 6 days) inhibited ethanol consumption during the 6 days of treatment by 25%, 50% and 75%, respectively, without modifying total fluid intake. We suggest that 5-HT3 receptor activation plays a permissive role in alcohol preference.
 
Article
Alcohol misuse is a common presentation to the Emergency Department (ED). The International Classification of Diseases ICD-10 for alcohol misuse, both under F10 and Y90/Y91, is not straightforward. The practicalities of coding ED attendances reveal an increasing detachment from ICD-10 (currently under review). Early identification [sometimes using blood alcohol concentrations (BACs)] and brief advice (IBA) can reduce unscheduled alcohol-related ED re-attendance. The UK Government Department of Health has implemented use of the terms 'Hazardous Drinking', 'Harmful Drinking' and 'Dependent Drinking' in its Public Service Agreements aimed at reducing harm by alcohol. Simplifying coding might increase IBA usage. We suggest that coding improvements in ICD-11 should update Y91 (currently 'clinical assessment')-with ICD-10 Y90 remaining for BAC to classify a patient's 'alcohol status'. Y90 and Y91 together would indicate the urgency for early IBA and/or speciality referral, aiming to reduce the prevalence of 'Dependent Drinking'.
 
Org 25935 decreases ethanol intake and preference in EP<60 male Wistar rats, n = 14-15. Data from Experiment 2, during baseline and Org 25935 administration, 6 mg/kg, i.p. Day 4-15, AD Day 16-29, reintroduction of Org 6 mg/kg Day 30-36. EtOH intake (a), EtOH preference (b), Water intake (c) and Total fluid intake (d). For statistics: see text.
Org 25935 decreases ethanol intake and preference in EP<60 male Wistar rats, n = 14–15. Data from Experiment 2, during baseline and Org 25935 administration , 6 mg/kg, i.p. Day 4–15, AD Day 16–29, reintroduction of Org 6 mg/kg Day 30–36. EtOH intake (a), EtOH preference (b), Water intake (c) and Total fluid intake (d). For statistics: see text.  
Article
Previous findings from our group indicate that accumbal glycine receptors (GlyRs) are involved in mediating the dopamine (DA) activating effects of ethanol (EtOH), and that administration of glycine locally into the nucleus accumbens (nAc) reduces EtOH consumption in EtOH high-preferring rats. The present study examines the influence of a systemically administered glycine reuptake inhibitor, Org 25935, on EtOH preference and intake, in male Wistar rats with an EtOH preference >60% (during continuous access to a bottle of EtOH, 6% v/v, and a bottle of water), called EP>60 rats, as well as in animals with an EtOH preference <60%, called EP<60 rats. Org 25935 is an inhibitor of the glycine transporter 1 (GlyT1) protein with negligible action on the glycine transporter 2 (GlyT2) protein. Both EP>60 and EP<60 rats were limited to drink 2.5 h/day. Org 25935 or vehicle was administered intraperitoneally approximately 40 min before the rats were presented to a choice of drinking EtOH or water. Org 25935 decreased EtOH intake and EtOH preference, as compared with vehicle, whereas water intake was unaffected. This effect was dose-dependent, developed gradually and was sustained for up to 40 days, also after introduction of an alcohol deprivation period. It is suggested that Org 25935, and possibly also other GlyT1 inhibitors, can represent a new pharmacological treatment principle for alcohol dependence or abuse.
 
Article
The O-dealkylation of various substituted alkoxyphenoxazones by liver microsomes from rats chronically fed ethanol is compared with that from pair-fed controls to determine whether there is any catalytic selectivity which could serve as an indicator for induction of cytochrome P-450j. Microsomes derived from animals pretreated with the better characterized inducers phenobarbital and Aroclor 1254 were also studied as positive controls. The specific activities (units/mg microsomal protein) but not the turnover numbers (units/nmol cytochrome P-450) were significantly increased by ethanol ingestion compared to pair-fed controls for methoxy-, ethoxy-, and pentoxy-resorufin O-dealkylation. Ethanol ingestion produced a significant increase in both specific activity and turnover number for the O-dealkylation of benzyloxy-resorufin. The degrees of induction of alkoxyresorufin-O-dealkylation activity measured for EtOH-induced microsomes range from 1.7 for methoxyresorufin to 4.8 for benzyloxyresorufin and are small in comparison to the values for phenobarbital and Aroclor 1254. This pattern of induction suggests that the minor isoforms induced by phenobarbital may be propagated by chronic ethanol ingestion.
 
Article
Dopamine D2 receptors in nucleus accumbens, olfactory tubercle and caudate nucleus of Sardinian ethanol-preferring (SP), and non-preferring (SNP) rats were compared by using [3H]YM-09151-2 binding. SP rats exhibited, in each area, lower density of D2 receptors than SNP and unselected Wistar (UW) rats. The results suggest that reduction in D2 receptors in SP rats may be relevant to their innate preference for alcohol.
 
Article
Research has demonstrated that diagnostic orphans (i.e. individuals who experience only one to two criteria of DSM-IV alcohol dependence) can encounter significant health problems. Using the SF-12v2, this study examined the general health functioning of alcohol users, and in particular, diagnostic orphans. Current drinkers (n = 26,913) in the National Epidemiologic Survey on Alcohol and Related Conditions were categorized into five diagnosis groups: no alcohol use disorder (no-AUD), one-criterion orphans, two-criterion orphans, alcohol abuse and alcohol dependence. Latent variable modelling was used to assess the associations between the physical and mental health factors of the SF-12v2 and the diagnosis groups and a variety of background variables. In terms of mental health, one-criterion orphans had significantly better health than two-criterion orphans and the dependence group, but poorer health than the no-AUD group. No significant differences were evident between the one-criterion orphan group and the alcohol abuse group. One-criterion orphans had significantly poorer physical health when compared to the no-AUD group. One- and two-criterion orphans did not differ in relation to physical health. Consistent with previous research, diagnostic orphans in the current study appear to have experienced clinically relevant symptoms of alcohol dependence. The current findings suggest that diagnostic orphans may form part of an alcohol use disorders spectrum severity.
 
Article
Time-series studies in 13 nations for the period 1950-72 indicated that suicide and homicide rates were usually, but not always, positively associated with the per capita consumption of alcohol.
 
Article
This study was conducted to compare the validity of a new screening instrument developed by the World Health Organization, the Alcohol Use Disorders Identification Test (AUDIT), to the short version of the MAST in 287 primary care patients. Subjects were classified as meeting a lifetime or current DSM-III diagnosis of alcohol misuse and/or dependence based on the DIS-R interview schedule. Using the original WHO guidelines (score of 11 or more), 37 (13%) scored positive on the AUDIT and 103 (36%) had a weighted score of 5 or more on the SMAST-13. The internal reliability of the AUDIT was 0.86, compared to the SMAST-13 at 0.85. Cut-off scores in this sample for current alcohol problems, utilizing Receiver Operating Curves, were 7-8 for the AUDIT and 5 for the SMAST. This study confirms the utility of the AUDIT for current alcohol problems and the SMAST-13 for lifetime or past problems in a rural clinical sample.
 
Article
Aims: Dopamine receptors are associated with reward and dependence towards alcohol. The polymorphisms of dopamine D2 receptor (DRD2) genes have been reported to be involved in susceptibility to alcoholism. Therefore, we investigated the association of three single-nucleotide polymorphisms (SNPs) in DRD2 and ankyrin repeat and kinase domain containing one (ANKK1) genes with alcohol dependence in Korean subjects, who were classified by the criteria of the Lesch typology. Methods: The DRD2 -141C (Insertion (Ins)/Deletion (Del)), exon8 (A/G) and the ANKK1 TaqIA (A1/A2) polymorphisms were genotyped in a case-control sample consisting of 245 alcohol-dependent (AD) patients and 110 healthy controls. AD patients were classified into four subtypes by the Lesch typology. The majority of them (77.1%) were Lesch type 1. Differences in genotype and allele frequencies were examined between the AD patients and the controls. Also those analyses were done between the Lesch type 1 group and the controls. Results: There were significant differences in the genotype and allele frequencies of -141C Ins/Del and TaqIA A1/A2 between the AD patients and the controls. However, there were no significant differences in genotype or allele frequencies of exon8 A/G between the AD patients and the controls. The -141C Ins/Ins and TaqIA A1+ variants were associated with Lesch type 1 AD patients. When analysing haplotypes of three SNPs, the odds ratio of -141C Ins-A-A1 was 2.286, while the odds ratio of -141C Del-G-A2 was 0.323. Conclusion: The present study showed a significant difference in DRD2 -141C and ANKK1 TaqIA polymorphisms between the AD patients and the controls. Our findings suggest that -141C Ins and TaqIA A1 alleles can be a predisposing factor for alcohol dependence in the Korean population.
 
Effects of ethanol on hormone-sensitive lipase (HSL) activity and cAMP accumulation in brown adipose tissue. Hormone-sensitive lipase activity (a) is expressed as nmol free fatty acids released per min per mg of tissue protein. cAMP accumulation (b) is expressed as nmol/mg of tissue protein. Acute ethanol treatment was a single dose of 2.5 g/kg i.p. 60 min prior to the assays. Chronic ethanol treatment consisted of 20% ethanol as sole drinking fluid for 4 weeks. The results are shown as means ± SEM from 20-24 mice for lean groups and 8-10 mice for obese groups. *P < 0.05, **P < 0.01 ethanol group < control; ¶P < 0.05, ethanol group > control; †P < 0.05, lean versus obese control.
Effects of ethanol on hormone-sensitive lipase (HSL) activity and cAMP accumulation in white adipose tissue. Hormone-sensitive lipase activity (a) is expressed as nmol of free fatty acids released per min per mg of tissue protein. cAMP accumulation (b) is expressed as nmol/mg of tissue protein. Acute ethanol treatment was a single dose of 2.5 g/kg i.p. 60 min prior to the assays. Chronic ethanol treatment consisted of 20% ethanol as sole drinking fluid for 4 weeks. The results are shown as means ± SEM from 20-24 mice for lean groups and 8-10 mice for obese groups. ¶P < 0.05, ¶ ¶P < 0.01 ethanol > control.
Article
Untreated (control) obese CBA mice had lower hormone-sensitive lipase (HSL) activity and cAMP levels in brown adipose tissue than normal lean mice, but white adipose tissue HSL activity and cAMP were similar in obese and lean mice. In the obese mice, chronic ethanol treatment increased HSL activity and cAMP levels in both brown and white adipose tissue to above the levels in lean mice. In the lean mice, chronic ethanol only stimulated white adipose tissue. UK 14304 [5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline: 2 mg/kg] inhibited HSL activity in both brown and white adipose tissues in lean mice, but a higher dose (3 mg/kg) was required to produce the same inhibition in obese mice. After chronic ethanol adipose tissues were more sensitive to UK 14304; only half the dose being required to produce the same level of lipase inhibition. We propose that, although chronic ethanol consumption increases cAMP levels in adipose tissue, particularly in obese mice, it also sensitizes the tissues to alpha(2)-adrenoceptor stimulation. These effects may explain the increased sympathetic nervous system activity observed in alcohol withdrawal.
 
Article
To evaluate the prevalence of externalizing symptoms, such as attention problems, aggression and delinquency in the offspring of alcoholics. A total of 146 children were divided into three groups with no (group 1, n = 28), one or two (group 2, n = 103) and three or more (group 3, n = 15) first- or second-degree relatives with an alcohol use disorder. The group comparisons revealed that the children of group 3 had significantly higher values for the Child Behavior Checklist scales of attention and delinquent behavioural problems. The results remained significant after controlling for some additional factors such as antisocial personality disorder and drug dependence in the parents.
 
Article
When heparinised whole blood was incubated with 5, 10, 45 or 180 microM 14C-acetaldehyde for 1 hr, an average of 33%, 34%, 33% and 41%, respectively, of the radioactivity was associated with red cells and the remainder with plasma. Although 71-80% of the radioactivity in the plasma was TCA-precipitable, only 0.9-3.1% was non-dialysable after 48 hr of dialysis, indicating that much of the acetaldehyde was reversibly bound to protein. When blood was incubated with 10-180 microM 14C-acetaldehyde for 1 hr and the plasma subjected to Sephacryl S300 gel filtration, 0.3-1.9% of the added radioactivity was found in the albumin and IgG fractions; this radioactivity is presumed to reside in both unstable and stable acetaldehyde-protein adducts. Plasma derived from whole blood which was incubated with 5-180 microM acetaldehyde and dialysed for 24 hr displayed cytotoxic activity against A9 cells. These data indicate that when 14C-acetaldehyde is incubated with whole blood, even at concentrations as low as 5-10 microM, a substantial proportion of the radioactive molecules form unstable cytotoxic adducts with plasma proteins and a much smaller proportion form stable adducts. Blood cells (mainly red cells) that were incubated with 14C-acetaldehyde were able to transfer radioactivity to cocultured K562 cells, supporting the possibility that not only acetaldehyde-modified plasma proteins but also acetaldehyde-modified blood cells may transport acetaldehyde and be cytotoxic in vivo.
 
Article
The influence of alcohol on the brain serotonergic system has been studied for several decades with some discordant results. The effects of continuous and constant treatment with ethanol on the rates of serotonin [5-hydroxytryptamine (5-HT)] synthesis in discrete regions of the rat brain were studied. 5-HT synthesis rates were measured using the alpha-[(14)C]methyl-l-tryptophan autoradiographic method. The rats in the experimental group were treated with 50% ethyl alcohol and those in the control group received distilled water. The fluid was delivered subcutaneously by implanted osmotic mini-pumps for 14 days at the rate of 5 micro l/h or 0.12 ml/day (0.06 ml of alcohol per day). Chronic ethanol treatment, as delivered in the present experiment, induced a significant increase in the rate of 5-HT synthesis in descending serotonergic cell bodies (raphe pallidum, raphe obscurus, raphe magnus), nigrostriatal structures, the hippocampus and cortices. No significant changes were observed in the dorsal and median raphe nuclei or pineal body. The results suggest that there may be differences in the regulation of 5-HT synthesis in different brain structures after 14 days of continuous (subcutaneous) injection of 50% alcohol. Chronic ethanol treatments using osmotic mini-pumps induce non-uniform increases in 5-HT synthesis in the rat brain.
 
Measures of alcohol-use in restricted (complete case) and unrestricted (all available data) samples
Risk factors for class membership (partially observed data for latent class models)
Predicting harmful/hazardous alcohol use at age 16 using patterns of alcohol frequency and consumption
Resulting patterns from LLCA (partially observed data).
Article
Teenagers in the UK report some of the highest rates of alcohol use in Europe. We identify patterns of alcohol use in early adolescence and relate these to hazardous and harmful alcohol use at age 16. In a UK birth cohort, we analysed repeated measures of alcohol use from age 13 to 15 in a sample of 7100 adolescents. Data on drinking frequency and typical consumption when drinking were modelled separately using a pair of latent class models. Classes of alcohol-use behaviour were contrasted across a range of risk factors and then to hazardous and harmful alcohol use as assessed using the Alcohol Use Disorders Identification Test scale at age 16. Heterogeneity in drinking frequency and consumption could each be captured with three classes corresponding to low, medium and high levels. In total, 14.2% were classified as high-frequency and 8.9% as high consumption alcohol users. Socio-demographic factors, maternal substance use and the young persons' use of tobacco and cannabis were associated with class membership. At age 16, 29% were drinking hazardously and a further 5.6% were assessed as harmful drinkers. Young people in the high drinking frequency or consumption class had a 9-fold increased risk of reporting harmful drinking at age 16. By the age of 16, a substantial proportion of teenagers in this sample were drinking at levels that could be considered hazardous or harmful for an adult. Patterns of alcohol exposure in early adolescence were strongly associated with later alcohol use. Altering drinking patterns in middle adolescence has the potential to reduce harmful use in later adolescence.
 
Article
Multi-buy is one method by which retailers discount alcoholic beverage sales. It is common in the UK. A Scottish ban on multi-buys had an immediate impact on sales. Because other methods for lowering price as a marketing tool will be used, the longer-term impact is unknown. Legislating a minimum price per unit of alcohol may have a longer lasting effect on overall alcohol consumption.
 
Article
We report the results of an "open' multicentre study evaluating the use, tolerability and therapeutic efficacy of the sodium salt of 4-hydroxybutyric acid (GHB) for the medium-term treatment of withdrawal symptoms in 179 patients with alcohol dependence followed up as outpatients. The follow-up of patients was 6 and 12 months after drug discontinuation. Following a daily oral administration of 50 mg/kg for approximately 6 months, no serious systemic or single-organ consequences leading to drug discontinuation were reported, and tolerability was fair in all patients. Eleven subjects (10.1%) showed craving for the drug and voluntarily increased their doses (6-7 times the recommended levels). GHB led to complete abstinence during drug administration in 78.0% of the patients. A significant reduction of compulsive desire ("craving') was observed in parallel, as deduced from evaluation of a specific questionnaire, the Alcohol Craving Scale. At follow-up examination, 43 of the treated subjects remained abstinent at 6 months, and 30 subjects were abstinent for 1 year after drug discontinuation.
 
Severity of nicotine dependence and bivariate odds ratios for outcome variables 
Associations of THC use with other psychoactive substances 
Article
To assess recent drug use through urine testing as well as the prevalence of tobacco and alcohol dependence among young males and to analyse the associations between tobacco dependence and cannabis use (delta-9-tetrahydrocannabinol, THC), tobacco dependence, and alcohol dependence as well as between THC use and other illicit drug use. Urine samples were collected, and nicotine and alcohol questionnaires were administered. Carbon monoxide was assessed in exhaled air. Data from young males from representative, selected districts of Lower Austria were recorded during the annual physical examination for mandatory military service. Out of all 18-year-old males in Austria 3.8% (n = 1902) were included in the study. Prevalence of recent illicit drug use, tobacco dependence (heavy smoking index, HSI), alcohol dependence (The 4-item cutting down, annoyance by criticism, guilty feeling, and eye-openers (CAGE) questionnaire), and associations between substance categories by means of logistic regression analyses were calculated. Alcohol abuse was found in 15.1% and alcohol dependence was found in 3.2%. According to the HSI 51.5% of males reported daily smoking, of whom 43.7% showed a mild level, and 7.8% a high level, of nicotine dependence. About 5.1% of the sample evidenced THC in urine. Opiates were identified in 2.7% of urine samples. Smokers showed a higher risk of THC use. THC users had a tendency to use cocaine and amphetamines more frequently than THC abstainers. Nicotine and alcohol dependence is common among young males. Biological assessment of illicit drug use seems to confirm previous questionnaire-based findings of associations between THC use and other illicit drugs. Urine testing seems to be an adequate method to analyse associations of THC use and other illicit drugs. In combination with questionnaires urine testing may be used for the assessment of associations of tobacco dependence and recent illicit drug use based on epidemiological surveys.
 
Frequencies and univariate associations between drunkenness frequency and significant explanatory variables 
Frequencies and univariate associations between drunkenness and significant explanatory variables 
Results of the multivariate analysis with YASR syndrome scales 
Article
To study the associations between drunkenness frequency and adaptive functioning, psychopathology and service use among 18-year-old Finnish boys in a nation-wide population-based study. Information about drunkenness frequency within the previous six months was collected from the Finnish boys born in 1981 (n = 2306) at the boys' obligatory military call-up in 1999. Self-report questionnaires were used to study demographic factors, adaptive functioning, risk behaviour, life events, and mental health service use. Psychopathology and adaptive functioning was assessed with the Young Adult Self-Report (YASR) questionnaire. Of the boys, 85% reported drunkenness within the previous 6 months. Most of the subjects were occasionally drunk: 39% reported drunkenness less than a month, and 35% less than once a week, while 10% reported being frequently drunk once a week or more often. Occasional drunkenness was associated with better adaptive functioning and psychosocial well-being in general. Refraining from drunkenness was associated with suicidal ideation and internalizing problems in the YASR scale. Frequent drunkenness associated with daily smoking, illicit drug use, and externalizing problems in the YASR scale, especially delinquent behaviour. In the multivariate analysis, number of friends, having a regular relationship and cigarette smoking had a linear association with frequency of drunkenness, while drunkenness-related alcohol use was less common among those with poor friendship quality. Among the participants, entering substance use treatment was rare (0.2%). Frequent drunkenness was found to be common among mental health service users. Among late-adolescent boys, occasional drunkenness is a normative alcohol use pattern and associates with social competence and good psychosocial functioning. Late-adolescent boys refraining from drunkenness in addition to those with frequent drunkenness may be in a need of mental health assessment. As entering substance use treatment is infrequent, establishing integrated services with multi-professional co-operation for late-adolescent males with frequent drunkenness is emphasized.
 
Numbers (percentages) of never-drinkers, according to gender and age, HSfE 1994-2003 
Fully adjusted percentages reporting as never-drinkers, by period, where there is evidence of effect modification by period (P < 0.10) 
Article
This paper describes prevalences, time-trends and characteristics of self-reported never-drinkers, during the period 1994-2003, focussing particularly on white adults aged 18-54. Data on 122,809 adults (18 + ) were obtained from the Health Survey for England (HSfE). Logistic regressions were used to estimate time trends in self-reported never-drinking, and associations between never-drinking and living alone, and educational qualification. Analyses were stratified by gender, age group and period. The overall proportion of white, female never-drinkers was 5.5%, rising monotonically with age. Proportions among men were much lower, with the lowest proportion (1.1%) in the 30-54 age group. Odds of never-drinking increased by 3% per year in those aged 30-54, a trend not explained by any covariates. Smaller increases were seen among those aged 18-29. Never-drinking was strongly associated with living with another adult and with lower qualification. The association with qualification increased over time among young women, and the association with living with another adult increased among men aged 30-54. Never-drinkers are a significant minority in England, whose prevalence rose, between 1994 and 2003, among adults aged under 55 years. The prevalence varies considerably by age, sex, and social characteristics, and the social discrepancies in never-drinking appear to be widening.
 
Article
The self-rating of drinking habits was compared to DSM-III-R diagnoses of alcohol abuse and dependence in 181 men with an average age (+/- SD) of 38.7 +/- 1.91 years. Results indicate that the 150 subjects without alcohol-related diagnosis (Group 1) rated themselves as 'non-problem drinker', in categories from 'non-drinker' to 'heavy drinker'. Among the 15 individuals with alcohol abuse (Group 2), none rated their drinking pattern as 'problem drinker'. Two (12.5%) subjects in the group of 16 individuals with alcohol dependence (Group 3) rated themselves as 'problem drinker', while most did not consider their drinking patterns as problematic. Within subjects who identified themselves as the same type of drinker (e.g. 'infrequent drinker', 'moderate drinker', etc ...), the quantity, frequency, and number of alcohol-related problems were higher in Groups 2 and 3, compared to Group 1. The self-rating of drinking habits using a single question failed to identify over 90% of the subjects diagnosed with alcohol use disorder (100% of those with alcohol abuse and 87.5% of those with alcohol dependence), and did not differentiate between levels of alcohol intake and number of alcohol-related problems for subjects who identified as a particular drinking type.
 
Wernicke (1881) Lehrbuch der Gehirnkrankheiten fur Aerzte und Studirende. Vol 2 Kassel Theodor Fischer 229–242. 
Article
A translation into English of the case history section of Carl Wernicke's original manuscript of 1881, with a discussion on its relevance for clinicians today. A copy of Carl Wernicke's original German text was obtained by one of the authors (CCHC) and translated into English from the old German by a professional translator. The translation was subsequently agreed by native German speaking referees, and minor changes made. The authors studied the translation in detail and concluded that Wernicke's description had stood the test of time. The diagnosis of Wernicke's Encephalopathy remains a clinical one.
 
Article
Relative contributions of earlier drinking and smoking vs mental health risk factors in predicting alcohol intake and heavy drinking in young adulthood were assessed. Higher average alcohol intake and heavy drinking (13 or more drinks on one occasion) in 1995 were significantly related to male gender and earlier high scores in 1990 of relief smoking, relief drinking, and their interaction. Parental alcohol problems, social group, perceived degree of social support, trait anxiety, number of negative life events, self-esteem, grade-point average, somatic symptoms score, or immature, neurotic, or mature defence style measured in 1990 did not predict alcohol intake or heavy drinking 5 years later. The findings suggest that alcohol intake and heavy drinking in young adulthood can be predicted by earlier self-reports on relief smoking and alcohol intake in adolescence.
 
Article
Mononuclear phagocytes from healthy human donors were incubated with or without ethanol (12-55 mM, initial concentration) in non-sealed wells in an atmosphere of 5% CO2 in air for 6 or 24 hr on day 1 or day 7 in culture. The actual ethanol concentration was assayed in the media at the beginning and at the end of each incubation period. The ethanol content was reduced to about 70% of the initial concentration after 6 hr incubation, and to below 20% after 24 hr incubation. Binding properties of the Fc-receptors, and their associated phagocytic activity, were tested after ethanol exposure of the cells. An initial concentration of 12 or 22 mM ethanol caused no differences from controls at any time in culture. Mononuclear phagocytes assayed on day 1 (= monocytes) showed reduced binding (60% of control) as well as internationalization (70% of control) of particles via the Fc-receptors after addition of 55 mM ethanol and incubation for 6 or 24 hr. Incubation in corresponding ethanol concentration for 6 hr had no effect on cells cultured for 7 days (= macrophages), whereas 24 hr incubation depressed the Fc-receptor function in these cells also. There were no changes in viability, morphology or spreading ability after ethanol treatment.
 
Article
The effect of Ro 19-4603, a novel potent partial inverse agonist of benzodiazepine (BZ) receptors, on voluntary ethanol intake was examined in a rat line selectively bred for ethanol preference (Sardinian ethanol preferring, sP, rats). Ro 19-4603, 1 mg/kg i.p., three times daily, reduced voluntary ethanol consumption by about 40% during 7 days of treatment, but failed to reduce water intake. The results suggest that the GABA/BZ receptor complex may play a role in the reinforcing property of ethanol.
 
Article
Blood group and secretor status were determined in 89 heavy drinkers receiving outpatient treatment at a district general hospital in north-west London, and compared with 89 age-, sex- and ethnic origin-matched controls drawn from a panel of 1700 patients from a contiguous general practice. There were no significant differences in the distribution of ABO types and secretor status in the two groups. Differences in salivary mucins were investigated by assaying levels of sialylated and non-sialylated Lewis antigens and blood group antigens ABH in both patients and controls. Although there were no differences in the mean antigen levels for H, A, B Le a and Le b antigens, using the monoclonal antibody 19.9 (to sialylated Lewis a antigen), higher levels were found for groups O and B/AB non-secretors and for group A secretors in alcoholics compared with controls. In addition, inappropriate Lea and 19.9 immuno-reactivities were detected in the saliva samples of a group O Le a−b− secretor alcoholic and a group A Le a−b− secretor alcoholic, respectively. It is suggested that these changes in glycosylation of salivary proteins relate to the increased parotid gland cell proliferation known to occur in chronic alcoholics.
 
Age-standardized male mortality rate, per 1000 populations (solid line), alcohol consumption, litres pure alcohol per capita 15 and older (dotted line), tobacco consumption, kilograms per capita (dashed line), 1911 – 2006. 
Article
Aims: Given the variety of relationships found between alcohol consumption and health using individual data (both negative and positive), the likely impact of changes in population-level alcohol consumption on health at the population level is not clear. This paper uses historical data from 1911 to 2006 to assess the relationship between changes in per-capita alcohol consumption on total male mortality in Australia. Methods: A longitudinal aggregate study using Australian per-capita alcohol consumption and mortality data from 1911 to 2006. Analysis is undertaken using autoregressive integrated moving average time-series methods. Results: Per-capita pure alcohol consumption has a significant association with male all-cause mortality, with an increase (decrease) of 1 l per-capita per year associated with a 1.5% increase (decrease) in male mortality (controlling for female mortality and smoking rates). The association between per-capita consumption and mortality was significant for all age groups, with a particularly strong effect among 15-29 year olds. Conclusion: These results place Australia in the group of countries for which a positive association between per-capita alcohol consumption and total mortality can be demonstrated. Thus, despite the beneficial effects of alcohol consumption on health found in many studies, increases in consumption at the population level in Australia are associated with declines in population health. Thus, per-capita alcohol consumption in Australia is a significant contributor to rates of male mortality, particularly among young adults, suggesting an interaction between per-capita consumption and risky episodic drinking. The policies aiming to reduce population-level alcohol consumption and episodic risky drinking have the potential to substantially improve population-health outcomes in Australia, particularly among young men.
 
Total, male and female mortality from liver disease in Australia from 1935 to 2006. 
Estimated effects of weighted alcohol consumption on overall, male and female cirrhosis mortality in Australia from 1935 to 2006 a
Trends in pure alcohol consumption per inhabitant age 15 years and above in total and for spirits, wine and beer in Australia from 1935 to 2006. 
Article
The aim of the study was to examine for Australia whether the link between population alcohol consumption and liver disease mortality varies over time, using 71 years of data. Overall and gender-specific rates of liver disease mortality were analysed in relation to total alcohol consumption as well as for different beverage types by using autoregressive integrated moving average (ARIMA) time series methods. Separate models were developed for the entire time period and for two sub-periods (1935-1975, 1976-2006). A 1-l increase in adult per capita consumption of pure alcohol led to a rise of ∼10% in overall liver disease mortality rates and a 11 and 9% increase in female and male liver disease mortality, respectively. The strength of the relationship between per capita consumption and liver disease mortality diminished over time. Spirits consumption was found to be the main driving factor in liver mortality rates between 1935 and 1975, while beer consumption was found to be the most significant predictor in liver diseases in the last three decades. In a comparative perspective, the effect of per capita alcohol consumption on liver disease in Australia is similar to the USA, Southern and Eastern Europe countries, but weaker than in Canada and western European countries. An increase in per capita alcohol consumption in Australia is likely to lead to an increase in liver disease. Changes in the most important beverage over the study period suggest substantial shifts in drinking patterns and preferences among the heaviest Australian drinkers.
 
Article
Professor Dharam P. Agarwal of the Institute of Human Genetics, University of Hamburg, Germany, has just passed away at the age of 64 years. His death is a severe loss to the scientific community and especially to those who were very close to him. Actually, Dharam never overcame the early death of his beloved wife, Krishna, who died shortly before him. He leaves behind two children, Kamayni, now an anaesthesiologist in Hamburg, and Prabhat, a senior scientist in Brussels. Dharam was Indian by birth, but lived in Germany for more than 35 years, first in Freiburg and later in Hamburg. But, truly, Dharam was a real world citizen, who had friends all over the globe. I met Dharam for the first time in the mid-1980s when he was already in Hamburg, shortly after …
 
Article
![][1] Martin’s death on 16 March 2010 at an early age has deprived the international community of addiction researchers of one of its leading and most influential figures. He was not only a skilled research worker but also a passionate believer in turning research into action. He worked tirelessly to influence public opinion both nationally and internationally. His research interests varied widely and included epidemiological and behavioural aspects of drug and alcohol misuse, sex industry workers and problems of HIV/AIDS. Through all of these, one can detect a desire to study individuals who have commonly been stigmatized or ostracized by society. His willingness to pursue causes which were neglected or even unpopular and to speak out against ill-informed opinion made him enemies as well as friends, but he was never daunted by this and his courage in this respect was outstanding. Martin was a mountaineer and one of his first acts on coming to Edinburgh in the early 1970s was to help form a mountaineering club called ‘The Jacobites’. At that time the Scottish Mountaineering Club did not admit women members, so Martin and some friends set up … [1]: /embed/graphic-1.gif
 
Article
Aims: The aim of this study was to estimate the overall impact of alcohol on US race- and sex-specific age-adjusted cirrhosis mortality rates and to consider beverage-specific effects that represent changes in drinking patterns over time, comparing states with large and small African-American/White cirrhosis mortality differentials. Methods: Using series data from 1950 to 2002, the effects of per capita alcohol consumption on cirrhosis mortality for African American and White men and women were estimated using generalized least squares panel models on first-differenced data. Granger causality tests explored geographic patterning of racial differences in cirrhosis mortality. Results: Cirrhosis mortality was significantly positively related to apparent consumption of alcohol, with an overall impact of 8-14%/l of ethanol. This effect was driven by spirits which were more strongly associated with mortality for African-American women and for African-American men in states with larger mortality differentials. This disparity first emerged in New York and spread through the Northeast and into Midwestern states. Conclusion: Differences in the contribution of alcohol to cirrhosis mortality rates suggest variation by race and gender in life-course patterns of heavy consumption, illicit liquor and spirits use, as well as birth cohort effects.
 
Highest frequency of alcohol consumption (combining individual responses going back in time) previously reported by 45-year-old (a) ‘never’ and (b) ‘occasional-only’ drinkers. 
The alcohol consumption categories used in this report, by the response options for items given at ages 16, 23, 33, and 42
Article
To investigate the validity of retrospective items used to distinguish people who have rarely or never consumed alcohol. The 1958 British Birth Cohort Study has followed 9377 individuals until age 45. Previous drinking (at 16, 23, 33 and 42 years) was investigated for two groups of 45-year-old non-drinkers, those reporting never having consumed alcohol ('never drinkers', n = 143, 1.5%), and having only consumed very infrequently ('occasional-only drinkers', n = 1149, 12.3%). 67% of never drinkers previously reported drinking, 25% were past weekly/daily drinkers; 56% of occasional-only drinkers reported weekly/daily consumption. The validity of the retrospective items was progressively questionable when presumed to cover longer time periods. Substantial measurement error was evident when identifying 'occasional-only' and 'never' drinkers using retrospective items covering the lifecourse. Researchers investigating potential health benefits associated with moderate drinking need to incorporate more sophisticated methods when identifying sub-groups of non-drinkers.
 
Article
We studied the relationship between drunk driving offences, school performance and adult educational achievements. Data from the Northern Finland 1966 Birth Cohort were linked with official criminality files and National Education registers. The cohort members were studied prospectively covering the period from pregnancy to 31 years of age. Drunk driving (one to two arrests) and recidivist drunk driving (three or more arrests) were treated as outcome variables and their relation to school performance was studied by cross-tabulation and to adult educational achievements (two levels of education) by logistic regression analysis, adjusting for parental social class and psychiatric morbidity. Drunk drivers had a statistically significantly worse school performance compared with controls. Male cohort members who had remained at the basic educational level had an elevated risk for drunk driving [odds ratio (OR) 3.0, 95% confidence interval (CI) 2.3-3.8]. The corresponding adjusted ORs for recidivist drunk driving and female drunk driving were 8.6 (95% CI 5.1-14.4) and 7.0 (95% CI 3.3-14.8), respectively. These results are unlikely to be directly causal; however, educational failures seem to be part of the complex causal pathway to drunk driving and even to alcohol-related disorders.
 
Article
To analyse the effects of age, period and cohort (APC) on light and binge drinking in the general population of Finland over the past 40 years. All analyses were based on six Drinking Habits Surveys between 1968 and 2008 of representative samples of the Finnish population aged between 15 and 69 (n = 16,400). The number of drinking occasions per year involving 1-2 drinks (light) and 4+ or 6+ drinks (binges) was used as a dependent variable in APC modelling. Descriptive cohort profiles and negative binomial models were used to assess the effects of APC. Descriptive cohort profiles differed for light and binge drinking. No substantial differences were found across cohort profiles for light drinking, while APC modelling predicted declining cohort and increasing period effects. Differences between cohorts were found for binge drinking, with predictions of slightly declining or increasing period and increasing cohort effects. Light drinking has increased over time for each cohort, with no substantial differences between cohort profiles. Binge drinking has increased with more recent cohorts and there are distinct differences between cohort profiles, especially among women.
 
Article
In a prospective population study of women in Gothenburg, Sweden, three examinations were conducted with 12-year intervals between 1968-1969 and 1992-1993. There were 1462 participants aged 38-60 years in the baseline study in 1968-1969, with a participation rate of 90.1%. This paper describes longitudinal changes and secular trends with respect to women's alcohol habits. An alcohol frequency questionnaire was validated at baseline and was re-administered at all examinations. Between 1968-1969 and 1980-1981, the proportion of alcohol abstainers decreased significantly both in 38-year-old and 50-year-old women. Women reporting alcohol intake at least once per week had higher socio-economic status and higher education than other women. Serum gamma-glutamyl transpepsidase concentration was higher in women with the heavier alcohol intake, while a number of potential cardiovascular risk indicators were higher in women with the lower intake. Daily intake of wine and spirits was about as common at all three examinations, whereas moderate intake of wine and spirits was more common in 1980-1981 and 1992-1993 than in 1968-1969. There seemed to be an increase in overall consumption of alcohol, mainly due to the increase in moderate drinking, but there was no indication of a large increase in heavy consumption of alcohol.
 
Article
A review is presented of British research related to alcohol use and misuse by adolescents in the period 1970 to 1991. The stability of alcohol use among this age group is emphasised by a succession of studies which indicate the normality of alcohol consumption among its members, most of whom drink in moderation. It is noted that a succession of 'moral panics' amplified in the popular media have led to public concern about an 'epidemic' of alcohol misuse by young people, but that research evidence does not sustain this popular supposition. Nevertheless, the available evidence does support the conclusion that alcohol misuse is a major problem for a small proportion of young people.
 
Article
This paper is concerned with underage drinking in the United Kingdom since 1971 and public policy relating to this issue. Research into youthful drinking and the relevant licensing laws are summarised. Data obtained from surveys and from statistics relating to offences against the licensing laws are presented, which together illustrate the difficulty in enforcing this legislation. It is concluded that there is no evidence that 'underage' drinking has either increased or decreased over the past 20 years, and that the criminal statistics give little indication of the regularity with which the licensing legislation is breached. Reasons for this include difficulty in assessing the age of young people and the complicated nature of the licensing laws.
 
Article
Neuropathy is one of the most severe side effects of disulfiram therapy. We report the case of a young man who developed a neuropathy following disulfiram administration, with a virtually complete recovery in 14 months. We then discuss 37 cases of disulfiram neuropathy reported since 1971. Evidence is given that: (1) there is no numerical sex prevalence, although the incidence of the disease in women is probably disproportionately high; (2) symptom onset latency is dose-dependent, being longer at 250 mg/day or less; (3) neurological deficits are also dose-dependent, being milder at 250 mg/day or less; (4) the two previous findings and single observations suggest that disulfiram neuropathy is a dose-dependent phenomenon; (5) recovery probably follows a course which depends primarily on the initial degree of impairment; (6) the genetic mechanism probably involves carbon disulfide and a hypothesis as to the possible biochemical mechanism is proposed; (7) chloral hydrate can bear a potentiation effect on neuropathy, and the association with disulfiram is best avoided. Further, we give guidelines for the differentiation between alcoholic and disulfiram neuropathy, advise prescribing the drug at 250 mg daily or less, if possible, and stress the utmost importance of an early diagnosis.
 
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Antoni Gual
  • Hospital Clínic de Barcelona
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Allan DAVID Thomson
  • University College London