Alcohol and Alcoholism - recent issues

The Pervading Influence of Alcoholic Liver Disease in Hepatology

Williams, R. — 2008-06-24

Rising levels of alcohol consumption in the UK are leading to substantial increases in morbidity and mortality from liver disease. Drinking is starting at an earlier age with binging an increasing common pattern, and women are overtaking men in the consumption. Manifestations of liver damage range from fatty liver to end-stage cirrhosis, but it is the increasing number of cases presenting with an acute alcoholic hepatitis (AAH) that are the cause for greatest concern. Development of well-validated prognostic scoring systems (Maddrey Modified Discriminant Function, Glasgow Alcohol Score) makes it possible to select those patients with AAH who are most likely to respond to corticosteroids. The results of early pilot studies of a number of anti-TNF agents are encouraging and with infliximab, reduction in portal pressure has been demonstrated to be consequent on controlling inflammatory processes in the liver. For those deteriorating to the stage of liver failure, artificial liver support with MARS is of value in correcting major pathophysiological disturbances and as a bridge to liver transplantation, the results of which both for end-stage alcoholic cirrhosis and for AAH—of which there is limited experience, are excellent. Even as the stringent regulatory measures needed to control rising alcohol consumption are introduced by government, the burden of liver disease in the UK will remain high for years to come.

The Short Allele of the Serotonin Transporter Promoter Polymorphism Influences Relapse in Alcohol Dependence

2008-06-24

Aims: The short (S) allele of the serotonin transporter gene promoter polymorphism (5-HTTLPR) contributes to the risk of alcohol dependence and co-occurring clinical features. We studied the putative link between this allele and relapse. Methods: 48 alcohol-dependent male patients were recruited and genotyped for the 5-HTTLPR. Relapse to alcohol drinking was monitored during 3 months after standardized withdrawal. Results: The S allele was significantly associated with relapse (p = 0.008) while no other factor that was measured played a significant role. Conclusions: The S allele of the 5-HTTLPR polymorphism may influence the risk of relapse in abstinent alcohol-dependent patients, possibly through intermediate phenotypes.

Distribution and Differential Induction of CYP2E1 by Ethanol and Acetone in the Mesocorticolimbic System of Rat

Sanchez-Catalan, M. J., Hipolito, L., Guerri, C., Granero, L., Polache, A. — 2008-06-24

Aims: The expression of cytochrome P4502E1 (CYP2E1) in the brain has been demonstrated in several regions, nevertheless there is a lack of specific studies on the constitutive expression and induction at the mesocorticolimbic system, the most relevant brain pathway in the context of drug addiction and alcoholism. Hence, we have performed a detailed study of the CYP2E1 expression and induction in three key areas of the mesocorticolimbic system of the rat brain: prefrontal cortex (PFC), nucleus accumbens (NAc), and ventral tegmental area (VTA). Methods: Expression levels of CYP2E1 were analyzed by Western blot. The induction of the enzyme in the selected brain areas by chronic acetone (1% v/v acetone in drinking water for 11 days) and ethanol (3 g/kg by gavage for 7 days) was also assessed. Results: (i) CYP2E1 was expressed in PFC, Nac, and VTA, with the order of magnitude of the levels being VTA ~ PFC > Nac, and approximately 3–13% of it was encountered in liver; (ii) acetone treatment significantly increased CYP2E1 expression in Nac, up to 212% of the control levels, whereas not significant changes were observed in VTA and PFC; (iii) chronic ethanol treatment only resulted in a significant induction of enzyme levels in VTA (124%). A similar enhancement, though not significant, was found to occur in NAc. Conclusions: CYP2E1 was present in the mesocorticolimbic system at different levels of expression. Chronic acetone and ethanol treatments are able to increase enzyme levels in specific areas of this system with the pattern of induction of the two agents being different.

Red Wine, but not Port Wine, Protects Rat Hippocampal Dentate Gyrus Against Ethanol-Induced Neuronal Damage--Relevance of the Sugar Content

Carneiro, A., Assuncao, M., Freitas, V. D., Paula-Barbosa, M. M., Andrade, J. P. — 2008-06-24

Aims: Chronic ethanol consumption leads to oxidative damage in the central nervous system inducing neuronal degeneration and impairment of brain functions. Nevertheless, it has been reported that grape polyphenols might prevent the alluded ethanol effects. We have reported that prolonged red wine intake improves hippocampal formation oxidative status, a finding not replicated using Port wine. Thus, we thought of interest to compare the effects of chronic ingestion of these wines in the morphology of dentate gyrus (DG) neurons that are particularly vulnerable to alcohol effects. Methods: Six-month-old Wistar rats were fed either with red wine or Port wine (both with 20% ethanol content, v/v), and the results were compared with 20% (v/v) ethanol-treated, ethanol/glucose and pair-fed control groups. After 6 months of treatment, the layer volumes of the DG and the total number of granule and hilar neurons were estimated. The dendritic trees of granule cells were also studied in Golgi-impregnated material. Results: The number of granule cells and the DG layer volumes were similar among all groups. However, the number of hilar neurons was reduced in Port wine, ethanol-treated and ethanol/glucose animals. Furthermore, the granule cells from these groups showed a decrease in the total dendritic length. Conclusions: Although the Port wine and red wine have similar amounts of flavanols with identical ability to protect against oxidative stress, the differences observed are probably related to the very dissimilar processes of wine production, leading in Port wine to a high content of sugars, which are known to have potent pro-oxidant effects.

Chronic Liver Disease--An Increasing Problem: A Study of Hospital Admission and Mortality Rates in England, 1979-2005, with Particular Reference to Alcoholic Liver Disease

2008-06-24

Aims: To determine time trends in hospital admissions for chronic liver disease in England between 1989/1990 and 2002/2003, mortality rates in England and Wales between 1979 and 2005, and the influence of alcohol-related disease on these trends. Methods: Hospital episode statistics for admissions in England were obtained from the Information Center for Health and Social Care and mortality data for England and Wales from the Office for National Statistics. Results: Hospital admission rates for chronic liver disease increased by 71% in males and 43% in females over the study period. This increase was largely due to alcoholic liver disease, admission rates for which more than doubled between 1989/1990 and 2002/2003. While there was a smaller rise for chronic viral hepatitis B and C, admission rates declined for hepatitis A, autoimmune hepatitis, and primary biliary cirrhosis. Mortality rates for chronic liver disease more than doubled between 1979 and 2005. Two thirds of these deaths were attributable to alcohol-related liver disease in 2005. The highest rate of alcoholic liver disease mortality was in the 45–64 age group, and the largest percentage increase between 1979 and 2005 occurred in the 25–34 age group. Conclusions: Hospital admissions and mortality in England from chronic liver disease are increasing. The underlying reasons are complex, but alcohol-induced liver disease makes a major contribution. There are clear social and health implications if the trend continues and addressing alcohol-related liver disease should be a public health priority.

Neuropsychological Function and Platelet Monoamine Oxidase Activity Levels in Type I Alcoholic Patients

Pombo, S., Levy, P., Bicho, M., Ismail, F., Cardoso, J M N. — 2008-06-24

Aims: To explore neuropsychological function in two differentiated patterns of platelet monoamine oxidase B (MAO B) activity in alcoholic patients. Methods: Neuropsychological examination and platelet MAO B activity extracted from blood were collected from 42 alcohol-dependent patients recruited in the alcoholism unit (NETER) of the Psychiatric Service of Santa Maria University Hospital. Results: Alcoholics presented significantly low levels of platelet MAO B activity, when compared with control subjects; platelet MAO B activity in alcoholics classified as "under average subgroup" showed significant lower scores in the Raven Progressive Matrix and higher scores in hostility dimension, when compared with platelet MAO B activity in "above average subgroup." Conclusions: Results suggested platelet MAO B as a trait marker also to type I alcohol-dependent patients and the two observed associations between platelet MAO B activity with neurocognitive measures of executive functions (nonverbal reasoning) and psychopathological dimension such as hostility may support the notion about the effect of platelet MAO B activity in the further development of an impulsive cognitive style.

Value of Ethyl Glucuronide in Plasma as a Biomarker for Recent Alcohol Consumption in the Emergency Room

2008-06-24

Aim: This emergency department (ED) study compared the value of plasma ethyl glucuronide (EtG) testing with the information about alcohol consumption obtained using the standard alcohol biomarkers gamma-glutamyltransferase (GGT) and carbohydrate-deficient transferring (CDT) and the AUDIT questionnaire. Methods: Minimally injured and clinically non-intoxicated male patients (n = 81) admitted to an ED were screened regarding their alcohol consumption, using the computerized AUDIT questionnaire and a paper-and-pencil assessment including the type, amount and time of alcohol intake. Blood samples were collected for determination of ethanol, EtG (LC-MS) and GGT in plasma and %CDT in serum (Axis-Shield %CDT immunoassay). Results: Out of the 81 patients, 23 (28%) were positive (≥8 points) on the AUDIT questionnaire. Only 3 (4%) showed a detectable ethanol concentration (range 0.01–0.07 g/L) but 31 (38%) showed a detectable EtG (0.16–39.5 mg/L). In four patients, EtG was detectable in plasma for >48 h after estimated completed elimination of ethanol. EtG was not correlated with the long-term biomarkers %CDT or GGT, or the AUDIT results, but with the time since estimated completed ethanol elimination. Conclusion: EtG testing in blood was found useful in the ED as a way to detect recent drinking, even in cases of a negative ethanol test, and to confirm abstinence from alcohol. This sensitive and specific short-term biomarker provides valuable additional information about individual drinking habits and might also be helpful to identify an alcohol hangover.

Clinical Characteristics of Carbohydrate-Deficient Transferrin (%Disialotransferrin) Measured by HPLC: Sensitivity, Specificity, Gender Effects, and Relationship with other Alcohol Biomarkers

Bergstrom, J. P., Helander, A. — 2008-06-24

Aims: The sensitivity and specificity of the relative disialotransferrin amount (%DST), considered the primary single target for measurement of the alcohol biomarker carbohydrate-deficient transferrin (CDT), were compared with the absolute CDT amount determined by the CDTect assay and with GGT and AST. Methods: Serum samples (n = 1387) were collected within the WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence. The subjects had been classified as "nondrinkers" (26%), "light/moderate drinkers" (50%), or "heavy drinkers" (24%) by use of the WHO/ISBRA Interview Schedule. An HPLC candidate reference method for CDT was used to quantify individual transferrin glycoforms. Results: No gender difference in %DST was noted for nondrinkers, but light/moderate and heavy drinking males had significantly higher levels than females. Of the alcohol biomarkers examined, %DST showed the strongest correlation with self-reported alcohol intake, except for female heavy drinkers. The area under the %DST ROC curve for male (0.83) and female (0.82) heavy drinkers was significantly higher compared with CDT by CDTect (0.68) and GGT (0.69). At the 40, 60, or 80 g ethanol/day thresholds, %DST showed lower test sensitivity in women but there was no significant gender difference in overall accuracy according to ROC curve analysis. Conclusions: %DST measured by HPLC showed overall higher sensitivity for "heavy drinking" and better correlation with recent high alcohol intake, compared with the absolute CDT amount, and GGT and AST. The observation that several "light/moderate drinkers" had elevated %DST levels and some also a measurable asialotransferrin indicated misclassification with the WHO/ISBRA Interview Schedule and emphasize the limitations of self-reports of drinking.

Audit Questionnaire as Part of Community Action Against Heavy Drinking

Kaariainen, J., Aalto, M., Kaariainen, M., Seppa, K. — 2008-06-24

Aims: The purpose of the present study was to find out how well the alcohol questionnaire, AUDIT, as part of a wide community action was noticed, and if it had any effects especially among heavy drinkers. Methods: As part of local community action campaign (‘Booze Weeks’), the AUDIT pamphlet was delivered to all households (90,000) in Tampere, Finland, and 500 randomly selected inhabitants were interviewed on telephone. Results: More than three quarters of those consuming alcohol had noticed the ‘Booze Weeks’ campaign and considered it necessary. Inhabitants who drank most frequently were also the most likely to have noticed the campaign and the AUDIT pamphlet. Conclusions: As part of a wide community action, home-delivered self-help material is often noticed especially by heavy drinkers. They might come to realize their own heavy drinking and seek professional treatment.

The Effect of the Binge Drinking Session on the Activity of Salivary, Serum and Urinary {beta}-Hexosaminidase: Preliminary Data

2008-06-24

Our report is the first to show that an acute ingestion (6 h) of a relatively large, yet tolerable dose of alcohol (120–160 g), significantly increases activity of total serum β-hexosaminidase (total β-HEX), β-HEX A and β-HEX B isoenzymes, as well as salivary total β-HEX and urinary β-HEX A, in eight infrequent binge drinkers. An increase in the activity of serum and urinary total HEX is mainly due to its secretory isoenzyme β-HEX A.

Pilot Study of Assertive Community Treatment Methods to Engage Alcohol-Dependent Individuals

Passetti, F., Jones, G., Chawla, K., Boland, B., Drummond, C. — 2008-06-24

Aims: Assertive approaches to treatment, which are becoming established for individuals with severe and enduring mental illness, may also be beneficial for engaging alcohol-dependent individuals without severe psychiatric co-morbidity, but so far there has been little research on this. This pilot study looked at the feasibility and potential benefits of introducing assertive community methods into the treatment of alcohol-dependent individuals with a history of poor engagement. Methods: Non-randomized parallel cohort study comparing a Flexible Access Clinic employing assertive community treatment methods with the Usual Care Clinic. Participants were individuals re-referred to our service after they had previously disengaged from treatment. Results: Patients receiving assertive treatment attended assessment a mean of 14 days earlier than those receiving treatment as usual. Treatment at the Flexible Access Clinic was associated with significantly higher rates of completing assisted alcohol withdrawal (35% versus 26%) and entering an aftercare placement (23% versus 14%). Aftercare was entered significantly earlier in the Flexible Access Clinic group (93 days versus 125 days). Conclusions: These promising results point to the feasibility and potential efficacy of assertive community treatment methods for alcohol dependence, and the need for a randomized controlled trial of effectiveness and cost effectiveness.

Valproate Treatment of Acute Alcohol Hallucinosis: A Double-Blind, Placebo-Controlled Study

Aliyev, Z. N., Aliyev, N. A. — 2008-06-24

Aims: The aim of this study was to compare the efficacy and safety of valproate (Depakine-Chrono) versus placebo for the treatment of acute alcohol hallucinosis. Methods: 10 days’ randomized, double-blind, parallel study was conducted; 40 patients with an ICD-10 diagnosis of acute alcohol hallucinosis were randomized to valproate (Depakine-Chrono) 3000 mg/day (n = 20) or placebo (n = 20). The primary efficacy measure was the Clinical Global Improvement (CGI) and the Positive and Negative Syndrome Scale (PANSS), subscale for hallucinosis. Results: Valproate-treated patients demonstrated a greater improvement than placebo-treated patients in CGI (P < 0.001) and PANSS subscale for verbal hallucinosis (P < 0.001). Conclusion: Valproate is effective in the treatment of acute hallucinosis and is generally well tolerated.

Childhood and Current Determinants of Heavy Drinking in Early Adulthood

2008-06-24

Aims: To explore the association of parental education, childhood living conditions and several adversities with heavy drinking in early adulthood, and to analyze the effect of the respondent's current circumstances on these associations. Method: The analyses were conducted in a sample of 1234 adults aged 18–29 years participating in the Finnish Health 2000 Survey (65% of the original representative two-stage cluster sample, N = 1894). The outcome measure was heavy drinking measured by g/week for pure alcohol (for men ≥280 g/week and for women ≥140 g/week). Results: 8% of young adult men and 5% of women were heavy drinkers. In both genders, parental alcohol problems and other childhood adversities, poor own education, and unemployment status increased the risk of heavy drinking. The impact of childhood on heavy drinking was partly independent and partly mediated by adult characteristics, in particular, for both genders, low level of education. Conclusions: Childhood adversities are associated with heavy drinking in early adulthood among both genders. Childhood social circumstances as well as low educational level and unemployment should be taken into account in planning preventive policies to tackle the harms caused by excessive alcohol use at the individual and population level.

Prevention of "Risky" Drinking among Students at a Brazilian University

2008-06-24

Aim: The aim of this paper was to compare the quantity and frequency of alcohol use and its associated negative consequences between two groups of college students who were identified as being "risky drinkers." Subjects were randomly allocated in a clinical trial to intervention or control groups. Methods: Risky drinking use was defined as Alcohol Use Disorders Identification Test (AUDIT) ≥8 and/or Rutgers Alcohol Problem Index (RAPI) ≥5 problems in the previous year. Students who had undergone the Brief Alcohol Screening and Intervention for College Students (BASICS) (N = 145 at baseline; 142 at 12 months, and 103 at 24 months, loss of 29.7%) were compared with a control group (N = 121 at baseline; 121 at 12 months and 113 at 24 months, loss of 9.3%), the nonintervention group. Variables included drinking frequency, quantity and peak consumption, dependence assessment, and family and friends’ abuse assessment. Results: Treated students at a 24-month follow-up decreased quantity of alcohol use per occasion and lowered AUDIT and RAPI scores. Conclusions: This is the first brief intervention work on risky drinking with college students in Brazil and the results are encouraging. However, it is difficult to conduct individual prevention strategies in a country where culture fosters heavy drinking through poor public policy on alcohol and lack of law enforcement.

Alcohol Consumption in The Netherlands in the Last Decade: Sharp Decreases in Binge Drinking, Especially among Youngsters

Garretsen, H.F.L., Rodenburg, G., van de Goor, L.A.M., van den Eijnden, R.J.J.M. — 2008-06-24

Aim: The aim of this study was to examine the development of alcohol consumption and ‘binge drinking’ in The Netherlands over the period 1997–2005. Methods: Data from three national population surveys commissioned by the Dutch Ministry of Health were compared. Results: Decreases in binge drinking have appeared, especially for youngsters, which are not explained by changes in the composition of the population according to religious orientation, and for which no other explanation can be given at present. Conclusion: Trends in binge drinking in The Netherlands can vary over relatively short spaces of time.

Mediators and Moderators of Parental Alcoholism Effects on Offspring Self-Esteem

Rangarajan, S. — 2008-06-24

Aims: The goal of the proposed study was fourfold: (i) to examine the effects of parental alcoholism on adult offspring's self-esteem; (ii) to identify and test possible mediators and moderators of parental alcoholism effects on the self-esteem of adult offspring; (iii) to examine the utility and relevance of attachment theory (Bowlby J. (1969) Attachment and Loss: Vol. 1. Attachment. New York: Basic Books) in explaining parental alcoholism effects on self-esteem and (iv) to address some of the methodological limitations identified in past research on adult children of alcoholics (ACOA). Methods: Participants (N = 515) completed retrospective reports of parental alcoholism, family stressors, family communication patterns, parental attachment and a current measure of self-esteem. Results: The results showed support for the detrimental effects of parental alcoholism on offspring self-esteem and offered partial support for family stressors as a mediator of parental alcoholism effects on parental attachment and parental attachment as a mediator of parental alcoholism effects on offspring self-esteem, respectively. Finally, support was found for family communication patterns as a moderator of the effects of family stressors on attachment. Conclusions: The study findings offer preliminary support for the utility of attachment theory in explicating parental alcoholism effects on the self-esteem of adult offspring. Findings from the present study make salient the need to consider factors beyond the identification of parental alcohol abuse when explicating individual differences in offspring self-esteem in adulthood. The identification of protective and risk factors can contribute to the development of optimal intervention strategies to help ACOAs better than simply the knowledge of family drinking patterns.

Peer-Group and Price Influence Students Drinking along with Planned Behaviour

Jamison, J., Myers, L. B. — 2008-06-24

Aims: To examine the theory of planned behaviour (TPB), as a framework for explaining binge drinking among young adults. Methods: One hundred and seventy-eight students in a cross-sectional design study completed self-report questionnaires examining attitudes to drinking, intention to drink and drinking behaviour in university. Binge drinking was defined for females (and males) as consuming ‘four (males—five) or more pints of beer/glasses of wine/measures of spirits’ in a single session. Results: Drinking alcohol was common; 39.6% of males and 35.9% of females reported binge drinking. The TPB explained 7% of the variance in intention to drink. Overall, 43% of the variance in intention, 83% of the variance in total weekly consumption and 44% of the variance in binge drinking was explained. The frequency of drinking and the drinking behaviour of friends significantly predicted intention to drink and binge drinking, respectively. Binge drinkers were influenced by peers and social-situational factors. Pressure to drink was greater for males; undergraduates were influenced by the size of the drinking group, ‘special offer’ prices, and the availability of alcohol. Conclusions: The TPB appeared to be a weak predictor of student drinking but this may be a result of how constructs were measured. With friends’ drinking behaviour emerging as a significant predictor of alcohol consumption, interventions seeking to reduce excessive drinking should target the role of peers and the university environment in which drinking occurs.

Residual Effects of Alcohol on Skilled Performance

Lemon, J. — 2008-06-24

A Response to the Paper 'Investigation of the "Hangover" Effects of an Acute Dose of Alcohol on Psychomotor Performance' by Lemon

Stephens, R., Ling, J., Heffernan, T. M., Heather, N., Jones, K. — 2008-06-24

Rethinking Substance Abuse. Edited by William R. Miller and Kathleen M. Carroll

Paton, A. — 2008-06-24

Evidence-Based Treatments for Alcohol and Drug Abuse: A Practitioner's Guide to Theory, Methods, and Practice. By Paul M. G. Emmelkamp and Ellen Vedel

Hore, B. D — 2008-06-24

Drinking in Context--Patterns, Interventions and Problems. Edited by G. Stimson, M. Grant, M. Choquet and P. Garrison

Ritson, B. — 2008-06-24

Alterations of serum brain-derived neurotrophic factor levels in early alcohol withdrawal

2008-05-03

Aims: Alcohol withdrawal-enhanced neurotoxicity contributes to the addictive process. Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal plasticity and learning. In this study, we explored the changes of serum BDNF levels in alcoholic patients at baseline and after one-week alcohol withdrawal. Methods: Twenty-five alcoholic patients were admitted for alcohol detoxification treatment, and 22 healthy control subjects were also enrolled. We collected blood samples of the patient group on the first and seventh day of alcohol withdrawal, and measured serum BDNF level with sandwich enzyme-linked immunosorbent assay. The severity of withdrawal symptoms was evaluated by the Clinical Institute Withdrawal Assessment-Alcohol, Revised every eight hours. Results: Serum BDNF levels did not differ significantly between alcoholic patients and control subjects. But BDNF levels were found to be significantly increased one week after alcohol withdrawal (from 13.9 ± 3.8 ng/ml to 15.4 ± 3.8 ng/ml, P = 0.03). A significant positive correlation was found between baseline BDNF level and baseline withdrawal severity (r = 0.45, P = 0.03). Conclusions: The present study suggests that elevated serum BDNF levels were found in early alcohol withdrawal, implying that BDNF may involve in neuroadaptation during the period.

Protective effects of sericin protein on alcohol-mediated liver damage in mice

Li, Y.-G., Ji, D.-F., Chen, S., Hu, G.-Y. — 2008-05-03

Aims: The purpose of this study was to investigate the protective effects of sericin protein (SP) on alcohol-induced hepatic injury in mice and the possible mechanisms. Methods: SP (0.375, 0.75 and 1.50 g/kg body weight) was dissolved in distilled water and given to mice by gavage 1 hour before the alcohol (56% wt/vol, 14.2 ml/kg b.w.) treatment for 30 days, then blood, urine and liver were collected, processed and used for alcohol concentration mensuration, various biochemical estimations and histopathological examination. Results: The concentration of alcohol evidently decreased in serum and increased in urine in SP treated mice as compared to alcohol-administered animals. Chronic alcohol administration resulted in significantly increase in the levels of transaminase (AST and ALT) and malondialdehyde (MDA) but decrease of glutathione (GSH), glutathione peroxidase (GSH-PX), catalase (CAT) and superoxide dismutase (SOD) in the serum and liver. Hepatic triglyceride (TG) also increased. When mice ingested high doses of SP (0.75 and 1.50 g/kg b.w.) the levels of antioxidant enzymes in the serum were restored to normal. However, hepatic CAT and GSH were still below normal, although a trend of significant increases was observed in comparison with alcohol treatment group. Conclusions: The results indicated that SP was able to hasten the alcohol elimination through urine directly and enhance the ethanol oxidation rate in liver. Simultaneously, SP may exert a protective effect against lipid peroxidation by scavenging reactive oxygen species and elevating the activity of antioxidant enzymes, in consequence prevented the peroxidative deterioration of structural lipids in membranous organelles, especially mitochondria and karyon.

Chronic alcohol feeding induces biochemical, histological, and functional alterations in rat retina

2008-05-03

Aims: Ethanol consumption originates a wide spectrum of disorders, including alteration of visual function. Oxidative stress is included among the mechanisms by which alcohol predisposes nervous tissue to injury. Retina, which is the neurosensorial eye tissue, is particularly sensitive to oxidative stress. Methods: In this study we analyze the effect of long-term alcohol consumption on oxidative stress parameters of the rat retina, and its correlation to retinal function, as well as to the expression of the antiapoptotic protein Bcl-2. We also study the protective effect of ebselen, a synthetic selenoorganic antioxidant. Results: Herein we show that ethanol has a toxic effect on rat retina associated with oxidative stress. Decreases in retina glutathione concentration and increases in malondialdehyde content in whole eye homogenate significantly correlate with ERG b-wave decrease and Bcl-2 overexpression. We also show how ebselen is able to prevent all the alterations observed. Conclusion: Chronic ethanol consumption induces oxidative stress in rat retina associated with an impairment of ERG and Bcl-2 overexpression, suggesting a role for glial cells. All these alterations in the rat allow the proposal of an alcoholic retinopathy in this species.

Alcohol exposure alters cell cycle and apoptotic events during early neurulation

Anthony, B., Zhou, F. C., Ogawa, T., Goodlett, C. R., Ruiz, J. — 2008-05-03

Background: Fetal alcohol exposure causes growth deficits, microencephaly, and neurological abnormalities. Although the effects of alcohol on developmental delay and growth-related deficits have been hypothesized, little is understood about how alcohol alters, in particular, the cyclin pathway within the cell cycle, which is critical to proliferation and apoptotic control. In this study, we examined cell cycle proteins pertinent to the G1–S phase transition and apoptosis, to determine if cell cycle misregulation can be attributed to apoptotic induction and growth defects. Methods: We examined cell cycle regulation during G1 and S-phase, and DNA fragmentation damage, using E14 dorsal root ganglia neural stem cells (DRG-NC), and cultured mouse embryos exposed to 200 and 400 mg/dl ethanol. Results: Alcohol-exposed DRG-NC demonstrated a dose-dependent increase in cells expressing increased cyclin D1 protein, and increased DNA fragmentation. Western blot analysis, using embryos, demonstrated an overexpression of cyclin D1, D2, and E2F1, key G1 to S-phase cell cycle regulatory components, and increases in p53, linking the cell cycle and apoptotic pathways. Bromodeoxyuridine incorporation indicated reduced DNA synthesis and growth in several embryonic regions. Propidium iodide staining demonstrated decreases in DNA content and increases in DNA fragmentation in several embryonic tissues. Conclusions: This study indicated that retarded growth of DRG-NC and embryos, induced by alcohol, is associated with altered expression of cell cycle and apoptotic proteins and concurrent inhibition of proliferation and increased DNA fragmentation. We suggest that alcohol induces an increase in cyclin D1 expression, premature S-phase entry, and disjointed DNA synthesis with increased apoptosis.

Associations of alcohol drinking and cigarette smoking with serum lipid levels in healthy middle-aged men

Wakabayashi, I. — 2008-05-03

Aims: The aim of this study is to determine whether influences of drinking alcohol on serum lipid levels are different in smokers and non-smokers. Methods: Subjects were 25,689 healthy male workers aged 40 to 59 years. Serum total and HDL cholesterol and triglyceride concentrations were measured and LDL cholesterol concentrations were estimated by using the Friedewald formula. The subjects were divided into three groups by average daily consumption of cigarettes (non-smokers; light smokers, less than 20 cigarettes per day; heavy smokers, 20 or more cigarettes per day) and by average daily alcohol consumption (non-drinkers; light drinkers, less than 30 g of ethanol per day; heavy drinkers, 30 g or more of ethanol per day). Results: In overall subjects, serum HDL, LDL and total cholesterol were significantly lower and triglyceride was significantly higher in heavy smokers than in non-smokers. In the smoker groups, serum total cholesterol was significantly lower in heavy drinkers than in non-drinkers, while no difference in total cholesterol was observed in non- and heavy drinkers of the non-smoker group. Both in the smoker and non-smoker groups, HDL cholesterol was higher and LDL cholesterol was lower in drinkers than in non-drinkers. The difference in LDL cholesterol between non-drinkers and drinkers was more prominent in smokers than in non-smokers. The above associations were not altered after the adjustment for age, body weight and alcohol intake. Conclusions: The results suggest that smoking increases the lowering effect of alcohol drinking on LDL cholesterol, but does not affect the relationship of alcohol drinking with HDL cholesterol.

Kinetics and isoforms of serum glutamate dehydrogenase in alcoholics

Kravos, M., Malesic, I. — 2008-05-03

Aims: The goal of this paper was to determine Glutamate dehydrogenase's (GLDH) increased activity and rapid decrease in alcoholics according to last consumption of alcohol as well as to confirm that quick normalisation cannot be a sign of hepatocyte necrosis and that GLDH from rough endoplasmic reticulum exists in the serum of alcoholics. Methods: GLDH activity was assed in 238 alcoholics admitted to hospital. A blood sample was taken from every subject three times: on admission to hospital, after 24 hours and after 7 days. We established our own reference activities for GLDH in serum, i.e., up to 124.0 nkat/l in males and 64.5 nkat/l in females. Results: Alcoholics were ascertained to have statistically significantly higher mean GLDH serum activities (men 351.53 nkat/L, women 296.08 nkat/L); the higher the level, the less elapsed time there was after the latest alcohol intake. There was an increased GLDH activity in 65.5% of alcoholics; furthermore, the percentage rose sharply to 72.2% with those who had last consumed alcohol within 48 hours. In the serum of alcoholics, it was found that, on average, it was 32.4% thermo-stable and 67.6% thermo-labile GLDH, which means that almost one third of GLDH serum originates from rough endoplasmic reticulum and rest from mitochondria. This is a completely new finding. Conclusions: A statistically significant fast decrease of GLDH serum activity after a break in alcohol consumption has been confirmed. It is estimated that increased GLDH activity in the sera of alcohol dependents and its fast decrease after total abstinence has been restored are specific for alcohol addiction.

Pathways to substance-related disorder: a structural model approach exploring the influence of temperament, character, and childhood adversity in a national cohort of prisoners

Lukasiewicz, M., Neveu, X., Blecha, L., Falissard, B., Reynaud, M., Gasquet, I. — 2008-05-03

Aims: Using Cloninger's model of personality, we aimed to specify the relative influence of the more biologically determined variables, temperament and character and more environmentally driven influence, childhood adversity in the development of addiction; and to compare patterns found among alcoholics with those found among drug addicts. Methods: We studied a group of prisoners, at a high risk of substance abuse and past history of childhood adversity. Using a stratified random strategy we selected (i) 23 prisons among the different types of prison in France, (ii) 998 prisoners. Each prisoner was assessed by two psychiatrists—one junior, using a structured interview (MINI 5 plus), and one senior, completing the procedure with an open clinical interview. At the end of the interview the clinicians met and agreed on a list of diagnoses. Cloninger's Temperament and Character Inventory was used to measure personality. Structural equations models, which have been advocated to disentangle the respective influence of complex risk factors, were used. Results: the "novelty seeking" temperament was a crucial vulnerability factor, for both alcoholics and drug addicts, in the same proportion. Character and childhood adversity played a significant part only in the development of drug abuse. Conclusions: In a prison population, a common biological loaded factor, novelty seeking is found both at the core of alcohol- and drug-related disorder whereas environmentally loaded factors play a greater role in drug problems.

Hippocampal volume loss in patients with alcoholism is influenced by the consumed type of alcoholic beverage

2008-05-03

Aims: The individual extent of structural brain tissue changes in patients with alcohol dependence is influenced by genetic factors, gender, age and possibly a dose/duration-effect. Aim of the present study was to investigate different types of alcoholic beverages with regard to hippocampal volume loss in patients suffering from alcoholism. Methods: We included 52 patients with alcohol dependence and divided them according to their preferred type of beverage consumption (beer, wine, and spirits). Hippocampal volumes were determined using volumetric high-resolution MR imaging. Results: There was a significant difference in hippocampal volumes between patients consuming different beverages (ANOVA: F = 7.454; df = 2; P = 0.0015) with the smallest volumes in the wine group, followed by the spirits group. Furthermore, patients with a preferred spirits consumption showed significantly higher plasma homocysteine levels (ANOVA: F = 3.39; df = 2; P = 0.042). Linear regression analyses revealed an association of homocysteine and hippocampal volume only in the group of patients preferring spirits (R² = 0.364; P = 0.008). Conclusions: Homocysteine-mediated excitotoxicity may be an important pathophysiological mechanism in ethanol-related brain damage, particularly in patients consuming wine and spirits. The extent of brain atrophy in beer consuming patients seems to be more moderate.

Comorbidity of alcohol and substance dependence with attention-deficit/hyperactivity disorder (ADHD)

2008-05-03

Aims: Attention-deficit/hyperactivity disorder (ADHD) is of great clinical importance not only because of its high prevalence but also due to the frequent comorbid illnesses that are connected with this disorder. Several studies were able to demonstrate that ADHD constitutes a significant risk factor for the exacerbation of habit-forming illnesses, i.e. addictions. Methods: We conducted a study on 152 adult patients with alcohol dependence (n = 91) or multiple substance addiction (n = 61) to determine whether or not these patients were affected by ADHD. For retrospective assessment of childhood ADHD, the WURS-k was used as well as the DSM-IV symptom checklist for ADHD. The CAARS was used to assess the persisting symptoms of ADHD in adults. Results: 20.9% (WURS-k) or 23.1% (DSM-IV diagnostic criteria) of the alcohol-dependent patients showed evidence of retrospective ADHD affliction in childhood. With the help of CAARS, ADHD was proved to be persistent in 33.3% of the adult patients. In the group of substance-addicted patients 50.8% (WURS-k) and 54.1% (DSM-IV) presented with diagnostic criteria for ADHD in childhood and 65.5% (CAARS) showed evidence of ADHD persisting in adulthood. Conclusions: These results reveal that habit-forming illnesses can be associated with a high comorbidity with ADHD, expressed in the form of alcohol abuse and also in consumption of illegal drugs. The results underline the great importance of early and adequate diagnostics and therapy of ADHD for the prevention of habit-forming illnesses.

Complaints about sleep in trauma patients in an emergency department in respect to alcohol use

Neumann, T., Neuner, B., Weiss-Gerlach, E., Spies, C. — 2008-05-03

Among other lifestyle problems, sleeping problems have been related to alcohol use. Aim: The aim of this study was to evaluate complaints about sleep in trauma patients in an emergency department and its relation to alcohol use disorders (AUD). Method: In an emergency department, trauma patients (1014 females, 1680 males) were screened using a computerized questionnaire addressing AUD (AUD identification test, AUDIT), smoking, drug and medication use, and sleep (presence of difficulties in falling asleep and/or sleeping through). Age, BMI, income, employment, partner status, and "feeling fit" were additionally assessed. Results: An AUDIT score ≥8 points was found in 24.2% of the males and 8.3% of the females. Complaints about sleep were reported by 28% and 34% of the patients, respectively. These complaints about sleep were more likely in males at-risk drinkers (AUDIT ≥ 8 versus 1–4 points (Adjusted odds ratio: AOR = 1.60, P = 0.001) or abstainers (AUDIT = 0 versus 1–4 points, AOR = 1.55, P = 0.029), and with increasing age (AOR = 1.01, P = 0.010), in patients not feeling "fit" (AOR = 2.15, P < 0.001), and users of pain (AOR = 2.24, P < 0.001) and sleep medication (AOR = 8.03, P < 0.001). In females, complaints about sleep were more likely with higher age (AOR = 1.04, P = 0.023), higher BMI (AOR = 1.04, P = 0.023), with not-feeling-fit (AOR = 1.87, P < 0.001) and sleep medication (AOR = 5.24, P < 0.001), and less likely in patients with a higher education (AOR = 0.57, P < 0.001). Conclusion: Complaints about sleep were reported frequently by trauma patients. There was an association between AUDs and sleep complaints (mainly problems about sleeping through) in males, but not in females.

Prognostic value of nutritional status in alcoholics, assessed by double-energy X-ray absorptiometry

2008-05-03

Objectives: This study was performed in order to assess nutritional status of 77 alcoholic patients. Methods: Patients underwent a total body double-energy X-ray absorptiometry (DEXA) analysis, with estimation of lean and fat mass at different parts of the body. Results: Lean mass, but not fat mass, was significantly reduced among alcoholics, compared to 31 age-matched controls, especially at right arm, legs, and total body. Lean mass at both arms was significantly related to liver function parameters (albumin, prothrombin activity, bilirubin) and, inversely, with ethanol consumption. The 24 patients who died during a follow-up period of 88 months showed less lean mass at both arms, trunk, and left leg, and also less fat at the left arm, than survivors. When right and left arm lean mass were classified in quartiles, Kaplan–Meier curves showed significant differences between dead and survivors. Left arm lean mass was the parameter which was independently related to mortality when encephalopathy was not included in a stepwise Cox regression analysis, but was displaced by this last parameter when it was also introduced in the analysis. Conclusion: lean mass is reduced in alcoholics, is related to liver function derangement and ethanol consumption, and is related to mortality.

Improving alcohol and tobacco history taking by junior medical officers

Proude, E. M., Conigrave, K. M., Britton, A., Haber, P. S. — 2008-05-03

Aims: We aimed to determine the effectiveness of individual feedback and group feedback in improving recording, assessment, and management of risky alcohol use and of tobacco smoking by Junior Medical Officers (JMOs). Method: Medical records of patients admitted by JMOs were examined for recording of alcohol use, alcohol withdrawal, intervention for alcohol, a consultation with the Drug and Alcohol team, tobacco use, and prescription of nicotine replacement therapy (NRT). In year 1, JMOs from hospital 1 received printed individual feedback on their own and their group's performance, while JMOs at hospital 2 attended a presentation of their group feedback. The following year, they reversed roles. Results: A total of 3025 patient records were examined for 130 JMOs. After individual feedback, the percentage of alcohol histories that were quantified rose significantly, from 69% to 82%. More smokers were detected, and NRT prescribing rates rose significantly. Group feedback showed no change. Logistic regression showed that JMOs were significantly more likely to record an alcohol history if located at the smaller hospital and in first year of hospital practice, if the patient was admitted during business hours, was male, and/or was younger than the median age of 70 years; JMOs were significantly more likely to quantify alcohol consumption after individual feedback, but this had no effect on tobacco history recording. Conclusion: Our study suggests that individual feedback on performance with education about desired standards is effective in improving the quality of recording of alcohol histories by Junior Medical Officers.

The latent structure of alcohol use disorders: A taxometric analysis of structured interview data obtained from male federal prison inmates

Walters, G. D. — 2008-05-03

Aims: Archival data from structured interviews of 1193 male prison inmates were subjected to taxometric analysis to determine the latent structure of the alcohol use disorder construct. Methods: Analyses were performed using three taxometric procedures: mean above minus below a cut (MAMBAC), maximum eigenvalue (MAXEIG), and latent mode factor analysis (L-Mode). Results: The outcomes were based on three indicators: (1) DSM-IV alcohol dependence criteria 1 and 2 (tolerance/withdrawal), (2) DSM-IV alcohol dependence criteria 3, 4, and 5 and DSM-IV alcohol abuse criterion 3 (loss of control), and (3) DSM-IV alcohol dependence criteria 6 and 7 and DSM-IV alcohol abuse criteria 1, 2, and 4 (negative social/psychological consequences). The outcomes revealed consistent support for a taxonic (categorical) interpretation of alcohol use disorders. Conclusions: There may be a taxonic boundary separating those who do and do not qualify for a diagnosis of alcohol dependence or abuse with important implications for diagnosis and treatment.

Gender differences in the efficacy of brief interventions with a stepped care approach in general practice patients with alcohol-related disorders

Reinhardt, S., Bischof, G., Grothues, J., John, U., Meyer, C., Rumpf, H.-j. — 2008-05-03

Aim: To analyse gender differences in the efficacy of stepped care brief interventions for general practice patients with alcohol problems. Methods: Data are part of "Stepped Interventions for Problem Drinkers," in which 10,803 patients from 85 general practitioners were screened using alcohol related questionnaires; 408 patients were randomized (32% were female) to a control (booklet only) or two different intervention groups: stepped care (feedback, manual, and up to three counselling sessions depending on the success of the previous intervention) and fixed care (four sessions). Response rate for the 12 months follow-up was 91.7%. Results: Regression analysis revealed a significant effect size only in women (P = 0.039). After excluding alcohol dependents and binge drinkers, an effect size (R²) of 0.031 (P = 0.050) in women and an effect size (R²) of 0.069 (P = 0.057) in men was obtained. Among the patients in stepped care who, by the first assessment point, had reduced drinking to within safe-drinking limits, there was a tendency for females to have achieved this more often than males (40% vs. 24%; P = 0.089). Conclusions: In a heterogeneous sample, the intervention was only effective for women. Women tended to profit more from the first, less intensive intervention than men. When analysis was limited to those reporting "at risk" average daily consumption and "alcohol abuse," the gender differences in efficacy appeared to be less, but the study was not sufficiently powered to affirm that.

Neurobiology and treatment in alcoholism--recent findings regarding lesch's typology of alcohol dependence

Hillemacher, T., Bleich, S. — 2008-05-03

Subtyping in alcohol dependence has become an important issue as studies have proposed different neurobiological mechanisms in alcoholism in the recent years. Studies have shown that alcohol dependence reflects a wide range of different phenotypes, including psychological, social, and neurobiological factors. Different ways of subtyping have been proposed in the last decades, one of them being Lesch's typology of alcohol dependence. Recent investigations have shown that different subtypes of Lesch's typology are associated with specific neurobiological factors which may have important implications for clinical practice. This applies in particular for genetic and neuroendocrinological factors, differences in the regulation of NMDA receptor-mediated glutamatergic neurotransmission, and in response to acamprosate and naltrexone treatment.

Improvement of knowledge, attitude, and behavior about oral health in a population of alcohol addicted persons

Barbadoro, P., Lucrezi, D., Prospero, E., Annino, I. — 2008-05-03

Aims: To improve knowledge, attitude, and behavior about oral health and oral cancer prevention in a population of alcohol-addicted persons involved in a residential rehabilitation program in Italy. Methods: A questionnaire was administered to obtain socioeconomic and oral risk factors data, and a complete dental examination was performed. A lecture on oral health risk factors and healthy behaviors was delivered. A pre–post test questionnaire was used to assess the short-term effectiveness of the intervention. Long-term effectiveness was assessed by a follow-up interview at 1 year from the intervention. The independent effect of several covariates on oral health at baseline and on the outcome of the intervention was evaluated. Results: Seventy-six individuals from the residential alcohol rehabilitation program participated in our study. About half had been addicted to alcohol for more than 10 years; 81.6% smoked at the time of survey; 31.0% declared that they never used toothbrushes or that they brushed less than once/day. We found an improvement of 25.0% in exact answers between the pre–post test questionnaire. At 1 year from the intervention, the 42 participants who reached follow up showed a great improvement in knowledge and attitude towards oral health. In particular, toothbrushing had become a daily routine after every meal for 67.1% of participants. Conclusions: Education of alcohol-dependent individuals in a rehabilitation setting may contribute to their attention to oral health and willingness to change habits.

Hazardous alcohol drinking in the former soviet union: a cross-sectional study of eight countries

Pomerleau, J., McKee, M., Rose, R., Haerpfer, C. W., Rotman, D., Tumanov, S. — 2008-05-03

Background: Hazardous consumption of large quantities of alcohol is a major cause of ill-health in the former Soviet Union (fSU). The objective of this study was to describe episodic heavy drinking and other hazardous drinking behaviors in eight countries of the fSU. Methods: Data from national surveys of adults conducted in Armenia, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Russia, and Ukraine in 2001 were used (overall sample size 18,428; response rates 71–88%). Heavy episodic drinking, high alcohol intake, drinking alcohol during the working day, and using illegally produced strong spirits were examined. Results: On average, 23% of men and 2% of women were defined as heavy episodic drinkers (≥2 l of beer or ≥750 g bottle of wine or ≥200 g strong spirits at least once every 2–3 weeks). This was more common in young males, women who are single or who are divorced/separated/widowed, in smokers, and in frequent alcohol drinkers. About half the respondents who drank strong spirits obtained at least some alcohol from private sources. Among drinkers, 11% of males and 7% of women usually took their first drink before the end of working day. Conclusions: Heavy episodic alcohol drinking is frequent in males throughout the region—although prevalence rates may have been affected by underreporting—but is still relatively rare in women. Alcohol policies in the region should address hazardous drinking patterns and the common use of illegally produced alcohol.

Prevalence and the factors associated with binge drinking, alcohol abuse, and alcohol dependence: a population-based study of chinese adults in Hong Kong

Kim, J. H., Lee, S., Chow, J., Lau, J., Tsang, A., Choi, J., Griffiths, S. M. — 2008-05-03

Aims: To examine the patterns of drinking, the relationship between binge drinking, alcohol abuse, and dependence, and the sociodemographic factors associated with problem drinking among Hong Kong Chinese. Method: An anonymous, random telephone survey was conducted on 9860 Hong Kong Chinese adults from April to June, 2006. Results: The age-adjusted prevalence amongst men for binge drinking was 14.4% with 5.3% of males being alcohol abusers and 2.3% dependent on alcohol. The corresponding figures for women were all lower at 3.6%, 1.4%, and 0.7%, respectively. Younger age groups showed the highest prevalence of these drinking problems. Among male binge drinkers, 18.7% were also alcohol abusers and 12.3% were alcohol dependent. Among female binge drinkers, 16% reported alcohol abuse and 9.9% reported dependence. Male binge drinkers were less likely to be older, less likely to be students but more likely to be employed in the service industry. Female binge drinkers were less likely to be over 60 years of age or married but more likely to be smokers. In both genders, smoking was significantly associated with the likelihood of binge drinking (OR = 3.6–12.3), alcohol abuse (OR = 3.0–12.1), and dependence (OR = 5.2–20.6). Conclusions: Although binge drinking has been well tolerated in Chinese culture, it is strongly associated with alcohol abuse and dependence in both genders in Hong Kong. Our findings suggest that prevalence of problematic alcohol consumption warrants greater promotion of alcohol harms awareness. Higher rates of heavy drinking in younger-aged individuals may reflect changing lifestyle behaviors and herald higher future levels of alcohol-related health and social problems.

Association between smoking and the risk of heavy drinking among young women: a prospective study

Morgen, C. S., Bove, K. B., Larsen, K. S., Kjaer, S. K., Gronbaek, M. — 2008-05-03

Aim: To address the association between smoking habits and the risk of later heavy drinking among young women. Methods: Repeated assessments of alcohol and smoking habits were obtained in 1991–93 and 1999–2000 in a Danish representative cohort in Copenhagen. A total of 6369 non- to moderate-drinking Danish women, aged 20–29 years at baseline, attended a follow-up examination and were included in the study. The risk of becoming a heavy drinker (more than 14 drinks per week) 8 years after enrolment was analyzed by means of logistic regression. Results: A total of 177 women became heavy drinkers during follow-up. Daily smoking at baseline was associated with an increased risk of becoming a heavy drinker 8 years later. Relative to nonsmokers, the adjusted odds ratios (OR) for becoming a heavy drinker associated with smoking 1–14, 15–24, or more than 24 cigarettes per day were 1.6 (95% confidence intervals (CI) 1.1–2.4), 1.7 (CI 1.1–2.6), and 2.3 (CI 0.9–5.9), respectively. Age at sexual debut modified the effect of smoking, and women with a debut before the age of 15 years had an adjusted OR of 2.9 (CI 1.1–3.9) compared to never-smokers while there seemed to be no effect among women with a sexual debut after the age of 18. In addition, relative to nondrinkers, all of the moderate (1–5 units per week), medium (6–10 units), and large (10–14 units) alcohol consumption at baseline were associated independently with becoming a heavy drinker 8 years later. Conclusions: This study suggests that smoking is an important predictor of later heavy drinking among young women and that this relatively elevated risk is most pronounced among women with an early sexual debut.

Alcohol consumption, abstaining, health utility, and quality of life - a general population survey in finland

2008-05-03

Aims: To examine the associations between alcohol consumption and utility-based health-related quality of life (HRQoL), subjective quality of life (QoL), self-rated health (SRH), and mental distress. Methods: Representative general population survey in Finland, with 5871 persons aged 30–64 years. HRQoL was measured with two health utility instruments (15D and EQ-5D), QoL and SRH were measured with RATING scales, and mental distress with a General Health Questionnaire (GHQ-12). Past alcohol problems were diagnosed with a structured psychiatric interview known as the composite international diagnostic interview (CIDI). Alcohol consumption was examined with a self-report questionnaire. Results: Negative associations between alcohol and well-being were observed on several measures for women consuming more than 173 g and men more than 229 g per week. Former drinkers scored worst on most measures, even in comparison to the highest drinking decile. For men, all statistically significant associations between moderate drinking and well-being disappeared when sociodemographic factors and former drinkers were controlled for. For women, moderate alcohol use associated with better SRH and EQ-5D as compared to abstainers. However, the possible health utility benefits associated with moderate alcohol consumption were of clinically insignificant magnitude. Conclusions: Failure to separate former drinkers and other abstainers produces a significant bias favoring moderate drinkers. As the possible health utility benefits of moderate alcohol use were clinically insignificant, it suffices to investigate mortality, when estimating the public health impact of moderate alcohol consumption using quality-adjusted life years.

Evidence-Based Treatments for Alcohol and Drug Abuse: A Practitioner's Guide to Theory, Methods and Practice. By Paul M. G. Emmelkamp and Ellen Vedel

Hore, B. D. — 2008-05-03

Alcohol Use Disorders. By Stephen A. Maisto, Gerard J. Connors and Ronda L. Dearing

Paton, A. — 2008-05-03

Alcohol-related deaths by occupation: what do data for england and wales in 2001-2005 tell us about doctors' mortality?

Baker, A. — 2008-03-26

Russell Bennetts. Alcohol: Price, Policy and Public Health

Bennetts, R. — 2008-03-26

The alcohol hangover-a puzzling phenomenon

Verster, J. C. — 2008-03-26

Cytogenetic effects of ethanol on chronic alcohol users

Demirhan, O., Tastemir, D. — 2008-03-26

Aim: Alcoholism is a significant public health problem that is also associated with a complex genetic trait. Fragile sites (FS) are potentially informative endpoints for the study of clinical disorders. We aimed to find chromosomal damages in chronic alcohol users for the purpose of finding the correlation between alcohol and chromosomal anomalies. Methods: The potential roles/effects of ethanol on chromosome(s) were assessed in this study by investigating its cytotoxic effects in lymphocyte cultures from chronic alcoholics and controls. Results: Alcoholics revealed a significantly higher frequency of FS and chromosomal aberrations (CA), and the FS clusters in specific chromosomal regions: 1q12, 1q21, 1q32, 2p13, 2q21, 2q31, 3p14, 3p25, 3q21, 4q21, 4q31, 5q31, 6p21, 7q22, 7q32, 9q13, 9q22, 10q22, 11q23, and 12q13. We also observed a significantly greater number of numerical and structural CA in alcoholics. The most frequent exchange types were deletions and polymorphic variations. CA could be due to the cumulative effect of both alcohol and smoking. The loci 1q12, 3p25, 4q31, 6p21, and 12q13 were not reported previously in alcoholics and may be hot spots for alcoholism. The overall FS frequencies were not statistically different between smoker and non-smoker controls, but smoking significantly increased the expression of 1p36, 3q21, and 5p15 sites. These sites have important clinical significance. Conclusions: Chronic alcohol abuse and the smoking habit can lead to chromosome damages that are especially influential on oncogenic regions, which may persist for a long time, and constitute a relevant factor of risk for the development of neoplasias.

Cytokines and lipid peroxidation in alcoholics with chronic hepatitis C virus infection

2008-03-26

A major cause of liver cirrhosis and hepatocarcinoma is chronic infection by hepatitis C virus. Ethanol consumption is the most significant environmental factor that exacerbates the progression of chronic hepatitis C to liver cirrhosis and hepatocarcinoma, perhaps due to increased cytokine secretion together with increased lipid peroxidation. In this study, we compare the intensity of lipid peroxidation (estimated as malondialdehyde (MDA) serum levels), the antioxidant status, (measured as glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities in red blood cells), and levels of cytokines derived from Th1 cells (such as interferon gamma (IFNG)), Th2 cells (such as interleukin (IL)-4), Th3 cells (such as transforming growth factor beta (TGF-β)), and IL-6, IL-8, and tumor necrosis factor (TNF)- in patients affected by chronic hepatitis C virus infection, 26 drinkers of alcohol and 40 nondrinkers of alcohol. Patients showed significantly higher TNF- (Z = 4.92, P < 0.001), IL-8 (Z = 4.95, P < 0.001), IFNG (Z = 2.81, P = 0.005), TGF-β (t = 2.12, P = 0.037), MDA (Z = 5, P < 0.001), but lower IL-6 (Z = 3.61, P < 0.001) and GPX (F = 4.30, P < 0.05) than controls, whereas no differences were observed regarding IL-4 (Z = 0.35, P = 0.72), GPX and SOD activities. Alcoholics showed significantly higher TNF-, but lower IL-4, MDA, and GPX, than nonalcoholics. TNF- was significantly related to albumin and prothrombin activity, whereas TGF-β was significantly related to MDA levels. Thus, cytokine secretion is altered in HCV infection. This alteration mainly consists of a stimulation of Th1 cytokines and an inhibition—or at least, no stimulation—of Th2 cytokines; these changes are especially marked among alcoholics with HCV infection, and are accompanied by raised TGF-β.

Association of alcohol dehydrogenase 2 and aldehyde dehydrogenase 2 genotypes with fasting plasma glucose levels in Japanese male and female workers

Dakeishi, M., Murata, K., Sasaki, M., Tamura, A., Iwata, T. — 2008-03-26

Aims: The objective was to clarify the effect of alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2) genotypes on the diabetic risk in Japanese workers. Methods: At the time of mandatory health checkup, the ADH2 and ALDH2 genotypes, as well as fasting plasma glucose (FPG) levels, body mass index (BMI), smoking habit, and weekly alcohol intake, were examined in 492 men and 183 women working at motor vehicle dealerships. Results: In using two-way analysis of variance to manipulate ADH2 and ALDH2 genotypes and alcohol intake (>70 g/week for men and >35 g/week for women), the FPG level after the adjustment for age, BMI, smoking habit, and another genotype was significantly higher in the men with ADH2*1/1 genotype than in those with the other genotypes, but there was no significant difference in the FPG level between the men with and without ALDH2*1/1 genotype. In contrast, the women with ALDH2*1/1 genotype had significantly lower FPG levels than those with the other genotypes, but there was no significant difference in the FPG level between the women with and without ADH2*1/1 genotype. Also, a significant interaction between ethanol intake and ALDH2 genotypes was seen only in the women. Conclusions: These findings suggest that genotypes of ADH2 and ALDH2 can modify the diabetic risk, irrespective of amounts of alcohol consumed. Also, there may be sex differences in the effect of these enzyme genotypes on glucose metabolism.

Invited Commentary * Serotonin transporter (SERT) brain density and neurobiological cloninger subtypes model: a lesson by human autoradiography studies

Leggio, L., Addolorato, G. — 2008-03-26

Cloninger proposed a neurochemical model of alcoholism suggesting that type 2 alcoholics have serotonergic deficits with intact dopaminergic system, whereas the type 1 alcoholics have defected dopaminergic system. The work by Storvik and colleagues recently published on Alcohol and Alcoholism shows some interesting differences on the SERT brain density between the type I and type II alcoholic subtypes. Critically, these findings on different serotonergic role in subtypes of alcohol-dependence revive the concept that alcohol addiction is a heterogeneous disorder associated with varying neurochemical abnormalities. Studies testing serotonergic medications in alcohol-dependent patients classified according to subtypes have shown interesting findings. Accordingly, the identification and standardization of alcoholic subtypes could be useful in guiding research on treatment. New developments in the neurobiological understanding of subtypes of alcoholic patients, could led to get the basis for a more personalized pharmacological therapy.

Effects of stress on emotional reactivity in hostile heavy social drinkers following dietary tryptophan enhancement

Nesic, J., Duka, T. — 2008-03-26

Aim: Because individuals high on hostility may be at risk for alcohol abuse due to serotonergic dysfunction and greater reactivity to stress, we examined the effects of acute dietary tryptophan enhancement and stress on mood and craving for alcohol in low-hostile (LoH) and high-hostile (HiH) individuals. Methods: Thirty-four LoH and 33 HiH heavy social drinkers [selection based on the Hostility scale from the Buss and Perry Aggression Questionnaire (1992)] received either tryptophan-enriched or control diet and underwent a stress-induction procedure. Trait differences between the two hostile groups were explored using personality, anxiety, and depression questionnaires. Mood, craving for alcohol, and salivary cortisol levels (CORT) were measured before and after tryptophan and after stress-induction. Heart rate (HR) was measured during stress-induction. Results: HiHs compared to LoHs scored higher on the depression and anxiety trait scales as well in the character dimension Harm Avoidance and reported more of stress exposure over the past month. They also showed more negative mood and higher craving for alcohol. Diet alone did not produce any subjective or physiological effects. Stress increased CORT, HR, negative mood, and craving for alcohol. HiHs displayed higher CORT increase and lower cardiovascular reactivity in response to stress compared to LoHs. Opposite to the predictions, tryptophan enhancement selectively facilitated stress-induced increase in craving in the HiHs. Conclusion: Among heavy drinkers HiHs report higher craving for alcohol and show greater reactivity to stress as measured by CORT and negative mood. The effects of stress on craving in HiHs may be mediated by a serotonergic mechanism.

Review * A review of the literature on the cognitive effects of alcohol hangover

Stephens, R., Ling, J., Heffernan, T. M., Heather, N., Jones, K. — 2008-03-26

Aims: Alcohol misuse is a prime social and health problem in the UK. This paper presents a critical review of literature on the performance effects in the morning after binge drinking – during the alcohol hangover. Several pathophysiological changes that both follow and outlast acute intoxication may give rise to alcohol hangover effects. We have identified 27 English language peer-reviewed studies that investigate aspects of psychological performance during alcohol hangover following controlled alcohol ingestion. However, the majority of studies had basic methodological shortcomings. Of eight laboratory studies rigorous enough to warrant serious attention, only two showed effects. We interpret these largely negative findings as evidence of an insensitivity that is intrinsic to laboratory-based studies of performance under the influence of alcohol. Several studies have investigated the cognitive consequences of hangover subsequent to naturalistic consumption, where participants have chosen what and where to drink. Although these studies have tended to show effects, participants were always informed at the outset that hangover effects were to be assessed, and participants knew which was the hangover condition. Under these circumstances expectancy effects have possibly contaminated the results significantly. Therefore, naturalistic alcohol consumption studies (and laboratory studies that did not employ a placebo) can be considered as being suggestive of hangover effects, but should not be interpreted as providing definitive evidence of such effects. In conclusion, although there is empirical evidence showing impaired performance as a result of the alcohol hangover, future studies should confirm these findings and overcome the shortcomings of previous research.

Illicit alcohol consumption and neuropathy - a preliminary study in Sri Lanka

Ferdinandis, T. G. H. C., De Silva, H. J. — 2008-03-26

Aims: To compare the effects on peripheral and autonomic nerve functions of Sri Lankan illicitly distilled alcohol consumption versus legal spirit consumption. Methods: Peripheral nerve conduction and autonomic nerve functions were assessed in 40 healthy control subjects and two groups of chronic heavy drinkers: 41 illicit spirit drinkers and 17 legal spirit drinkers. Results: Lower-limb motor and sensory nerve conduction parameters were affected in both groups of alcoholics. When compared with controls, in illicit spirit drinkers the mean heart rate indexes of all parasympathetic tests were lower while in legal spirit drinkers the heart rate response to standing was affected. There were no differences in the results of the above tests when the two groups of heavy drinkers were compared. Conclusions: Though chronic alcoholism results in peripheral and autonomic nerve damage, the damage caused by consumption of illicitly distilled spirit is not worse than the damage caused by consumption of legal spirits.

Review * Wernicke's encephalopathy revisited * Translation of the case history section of the original manuscript by Carl Wernicke 'Lehrbuch der Gehirnkrankheiten fur Aerzte and Studirende' (1881) with a commentary

2008-03-26

Aims: 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. Methods: 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. Results: The translation was subsequently agreed by native German speaking referees, and minor changes made. Conclusions: 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.

Wernicke's encephalopathy: 'plus ca change, plus c'est la meme chose'

2008-03-26

Aims: To develop clinical guidelines to identify individuals who misuse alcohol and are at risk of developing Wernicke's Encephalopathy (WE). Method: Non-systematic literature review of studies which includes a careful clinical record of the development of signs and symptoms of thiamine deficiency and in which the diagnosis of WE has been confirmed at autopsy. Results: The review of the clinical findings in cases of WE, diagnosed at autopsy, shows a consistent pattern of signs and symptoms. The pattern appears to be similar regardless of whether the thiamine deficiency is related to nutritional problems alone or associated with alcohol misuse. Conclusions: The assessment of the degree of thiamine deficiency and the diagnosis of WE remain a clinical evaluation, and guidelines are suggested to help the clinician. Since neurotoxicity due to the metabolism of excessive alcohol in patients with chronic and severe alcohol dependence may be an important factor in determining long-term outcome of treatment, this must form part of the overall evaluation.