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Different effects of stress on alcohol drinking behaviour in male and female mice selectively bred for high alcohol preference.

AIMS: The purpose of the present study was to examine the effects of stress on alcohol drinking behaviour in male and female mice with a genetic predisposition toward high alcohol preference (HAP2 line). METHODS: Alcohol-naïve male (n = 22) and female (n = 23) HAP2 mice were assigned to a restraint stress or no stress control group. Stress was initially applied for 2 h per day on 10 consecutive days. All mice were then given daily 2 h limited-access to a 10% v/v alcohol solution or water, with food freely available, for 21 days. Over the next 20 days, 2 h restraint stress was applied every other day immediately prior to 2 h access to alcohol and water. On intervening days, all mice received 2 h access to alcohol and water in the absence of stress. Following this phase of the study, the effects of restraint stress on acoustic startle reactivity was assessed in all mice. Finally, all mice were given continuous access to alcohol and water for 8 days. RESULTS: Ten days of prior stress exposure did not significantly alter the acquisition of limited-access alcohol drinking. Subsequent exposures to intermittent restraint stress produced subtle but consistent effects on alcohol intake that differed in males vs females: stress increased alcohol intake in males and decreased alcohol intake in females. Restraint stress did not alter acoustic startle reactivity. Under continuous-access conditions after stress termination, the stress-induced increase in alcohol intake in males became more robust; however, in females, alcohol intake returned to the control group level. CONCLUSIONS: These findings suggest that the effects of stress on alcohol drinking in mice with a genetic predisposition toward high alcohol preference depend on sex.

Acoustic Stimulation↗

Increased P3 amplitudes induced by alcohol-related pictures in patients with alcohol dependence.

BACKGROUND: Alcohol craving, a key element in alcohol dependence, is recognized as being a kind of motivational or emotional state. It is meaningful in research and clinical practice involving alcohol dependence to explore ways of measuring alcohol craving. The aim of this study was to measure the P3 event-related potentials induced by alcohol-related pictures in patients with alcohol dependence; these potentials are considered to constitute a neuronal correlate of alcohol craving. METHODS: On the basis of our previous study, six alcohol-related pictures and six neutral pictures were chosen as the visual stimuli. Each set of stimuli consisted of alcohol-related or neutral pictures as the target stimuli and same-sized checkerboards as the nontarget stimuli. The stimuli were presented by using the oddball paradigm for 300 msec, with an interstimulus interval of 1000 msec, in 12 controls and 16 abstinent patients with alcohol dependence. Each electroencephalography session consisted of three blocks: a practice block, a neutral block, and an alcohol-craving block. RESULTS: The amplitudes of P3 elicited by the alcohol-related pictures were significantly larger than those elicited by the neutral pictures in the patients with alcohol dependence, whereas there was no significant difference according to the stimuli in the P3 amplitudes of controls. Repeated-measures ANOVA on the amplitudes of P3 revealed that there was a significant interaction effect of block by subject group. CONCLUSIONS: These results suggest that event-related potentials can be used as a neuronal correlate of alcohol craving in alcohol-dependent patients. Future investigations will be needed to assess the frequency of relapse in the patients included in this study, to elucidate the meaning of the observed results with regard to the therapeutic outcomes.

Adult↗

EEG alpha and level of response to alcohol in Hispanic- and non-Hispanic-American young adults with a family history of alcoholism.

OBJECTIVE: A person's level of response to alcohol is associated with family history of alcoholism, ethnic heritage and electroencephalogram (EEG) phenotype. The present study's aims were to investigate EEG alpha and response to alcohol in Hispanic-American and non-Hispanic-American young adults. METHOD: EEG power in the slow and fast alpha frequency ranges (7.5-9 Hz, 9-12 Hz) was obtained at baseline and at 74 minutes following the administration of alcohol to Hispanic-American (n = 79) and white non-Hispanic-American (n = 208) young adult men and women (18-25 years old), all of whom had a family history but no personal history of alcohol dependence. Measures of breath alcohol concentrations and subjective responses to alcohol (Subjective High Assessment Scale [SHAS]) also were ascertained. RESULTS: Alcohol was found to produce significant effects on EEG power in the slow (F = 79.5, p < .0001) alpha frequency range. Although no overall effects of alcohol were found in the fast alpha frequency range, Hispanic participants had decreases in EEG fast alpha activity following alcohol administration, whereas non-Hispanics had alcohol-induced increases in power in this frequency range (F = 4.0, p < .04). EEG power, in the fast alpha frequency range (9-12 Hz) at baseline, also was found to be negatively associated with level of response to alcohol, as indexed by SHAS scores (F = 5.2, 2/283 df, p < .023). CONCLUSIONS: Previous studies in Native Americans, Asians and Euro-Americans have suggested genetic stratification in EEG response to alcohol as well as significant associations with family history of alcoholism. The present results extend previous studies to Hispanics and further confirm that increased EEG alpha power at baseline is predictive of a less intense response to alcohol, as indexed by the SHAS.

Adolescent↗

Structural equation model tests of patterns of family interaction, peer alcohol use, and intrapersonal predictors of adolescent alcohol use and misuse.

A survey of 1,340 students in grades six through twelve was conducted to test, in the context of structural equation models, the predictive validity of a theoretical model of antecedents of adolescent alcohol use and misuse. Constructs including parents' alcohol use, older siblings alcohol use, parents' approval of students alcohol use, older sibling approval of students alcohol use, peer use and approval of alcohol use (PUA), parental nurturance, parental permissiveness, child's grade in school, susceptibility to peer pressure (SPP), and deviant self-image, were included. The final iterations of the models accounted for more than half of the variance in both alcohol use and alcohol misuse. In a standardized solution, the two largest direct effects on both adolescent alcohol use and misuse were from SPP and PUA. When a seven item measure of SPP, including three items specific to alcohol use was used, the SPP latent variable accounted for a somewhat greater percentage of the variance in adolescent alcohol use and misuse than did the latent variable of PUA. When the three alcohol-specific items were deleted from SPP, however, PUA accounted for more variance than SPP. Other predictors, including parental behaviors, proved to be significant when their indirect effects were evaluated. Models predicting alcohol use and alcohol misuse were similar. SPP, PUA, and other significant predictors should be included in future models predicting adolescent alcohol use and misuse, as well as in future interventions targeting these behaviors. Longitudinal studies should be used to test these findings. Evaluation of prevention should include examination of possible interactions of these predictors with each other and with subject subgroup classifications.

Adolescent↗

Detectable blood alcohol after a motor vehicle crash and screening for alcohol abuse/dependence.

OBJECTIVE: To determine the percentage of patients hospitalized after an alcohol-related motor vehicle crash (MVC) who underwent a screening evaluation for alcohol abuse/dependence and had a diagnosis of alcohol abuse/dependence. PATIENTS AND METHODS: Medical and emergency trauma records were reviewed retrospectively for 1994 through 1996 to identify patients who were hospitalized as a result of being involved in an MVC with any detected blood alcohol at the time of admission to a large midwestern Level I trauma center. The primary outcome measure was the performance of alcohol abuse/dependence screening by a psychiatrist or a chemical dependency counselor. A univariate analysis was performed to identify factors associated with the performance of alcohol abuse/dependence screening. The Fisher exact test and the 2-sample rank sum test were used in the analyses. RESULTS: Of the 294 study patients, 78 (26.5%) underwent a screening evaluation for alcohol abuse/dependence by a psychiatrist or a chemical dependency counselor during hospitalization, and 69 (88%) of the 78 patients screened had a diagnosis of alcohol abuse/dependence. Factors associated with the performance of alcohol abuse/dependence evaluation included a known prior history of alcohol abuse, suspicion of alcohol consumption documented by emergency department personnel, higher blood alcohol level at admission, and longer length of hospitalization (all P < .001). CONCLUSION: While the high rate of alcohol abuse/dependence may be explained partially by distinguishing factors in those screened, these findings suggest that routine alcohol abuse/dependence screening of persons presenting with a detectable blood alcohol level following an MVC may identify patients who would benefit from a chemical dependency intervention.

Accidents, Traffic↗

Limited access alcohol drinking in high- and low-alcohol preferring selected lines of mice.

BACKGROUND: Selection studies and genetic analyses of drinking behavior in rodents often involved unlimited access to alcohol over a period of weeks, with water and food freely available. Most studies investigating the pharmacology of alcohol drinking, on the other hand, use procedures in which access to alcohol is limited to a particular time each day. Reconciliation of findings between these two conditions likely depends on their sharing common genetic mechanisms as indicated, for example, by covariation in response to selection. To this end, high- and low-alcohol preferring (HAP and LAP, respectively) mice, selected for differences in 24-hr access alcohol drinking over a 4-week period, were subjected to a limited access alcohol drinking protocol. METHODS: During 2-hr sessions, mice had access to various concentrations of alcohol (7-15%, v/v) in the home cage for 2 hr a day, with ad libitum access to food and water. Additional sessions were conducted with no food present. RESULTS: Although both strains consumed alcohol and water during these sessions, HAP mice drank far more alcohol than did LAP mice. HAP but not LAP mice drank alcohol at a high rate early in the session compared with later in the session. Additionally, HAP mice responded to changes in alcohol concentration, whereas LAP mice did not. Removal of food did not influence alcohol drinking, although water drinking decreased following food removal. HAP mice reached appreciable blood alcohol concentrations after limited access. CONCLUSIONS: These findings indicate that in these selectively bred mice, alcohol drinking during limited and unlimited access may be genetically related, and that drinking during limited access sessions in HAP mice is likely for the pharmacological properties of alcohol.

Alcohol Drinking↗

Sertraline treatment for alcohol dependence: interactive effects of medication and alcoholic subtype.

BACKGROUND: Characteristic behaviors of some alcohol-dependent individuals, e.g., binge drinking, comorbid psychopathology, and some types of alcohol-related problems, have been linked to abnormalities in serotonergic neurotransmission. However, studies that have evaluated serotonergic pharmacotherapy for reducing drinking have yielded conflicting results. One explanation for these findings is a general failure to distinguish alcohol subgroups that may be differentiated on the basis of serotonergic abnormalities. However, in 1996, Kranzler and colleagues reported that Type B alcoholics, who are characterized by high levels of premorbid vulnerability, alcohol dependence severity, and comorbid psychopathology, showed less favorable drinking outcomes in response to treatment with fluoxetine, a serotonin reuptake inhibitor, than with placebo. This medication effect was not seen in Type A alcoholics, i.e., those with lower risk/severity of alcoholism and psychopathology. The aim of the present study was to explore the validity of differential responding by alcohol-dependent subtypes using the serotonin reuptake inhibitor, sertraline. METHODS: A k-means clustering procedure was applied to a sample of alcohol-dependent subjects enrolled in a 14-week, placebo-controlled trial of 200 mg/day of sertraline, classifying them into lower-risk/severity (Type A: n = 55) and higher-risk/severity (Type B: n = 45) subgroups. RESULTS: A significant interaction between alcoholic subtype and medication condition was found, confirming the findings of Kranzler and colleagues that alcoholic subtypes responded differentially to serotonergic medication. Somewhat at variance with their results, however, the present study showed that the lower risk/severity (Type A) subjects had more favorable outcomes when treated with sertraline compared to placebo. CONCLUSIONS: Alcoholic subtypes differentially responded to sertraline when used as a treatment to reduce alcohol drinking, with one subtype having more favorable outcomes. Subtyping alcoholics may help to resolve conflicting findings in the literature on serotonergic treatment of alcohol dependence.

Adolescent↗

Alcohol in alcoholic liver disease is a causative factor for development of allergic skin manifestations.

BACKGROUND: We frequently observed allergic skin reactions in patients with documented history of alcoholic liver disease (ALD). To assess the potential association between alcohol-induced liver damage and urticaria a prospective randomized trial investigating immunologic parameters in various stages of alcoholic liver disease was designed. Fifty patients were available for analysis. METHODS: By means of a multivariate discriminant analysis seven out of a number of laboratory and clinical parameters (level of serum proteins, serum globulins, gamma globulins, albumin/globulin ratio, and immunoglobulins A, E, and G) have been found important for analysis. They were compared with age, general clinical status, degree of progression of alcoholic liver disease, and frequency of appearance of type I skin reactions. Results were further processed by means of logistic general linear models, Chi-square test, and summarized in a structural equation model. RESULTS: Alcoholic liver disease does not influence IgA, IgG, and A/G Index directly, but it increases levels of IgE. About 13% of variance of IgA, IgG, and A/G Index are affected by group membership only in non-alcoholic liver disease, and 27% of variance of IgE can be explained by alcoholic liver disease. There were striking differences in IgE content between alcoholic liver disease and control groups. Degree of liver disease had a negative impact on A/G Index, and on IgA, and a positive on IgG. About 16% of variance can be explained by degree of liver disease. IgE is not degree related. Alcoholic liver disease as a disease was found as the most important predictor of skin reactivity (p = 0.0046). Of all immunologic parameters investigated IgE followed by A/G Index was found as the most significant predictor of allergic skin reactions. The extent of alcoholic liver disease plays not a role in allergic skin manifestations. Alcoholic nature of liver disease itself is a significant factor causing allergic skin reactions (p = 0.0002), but alcoholism itself as an independent factor contributes to increased incidence of skin allergies. CONCLUSIONS: Alcoholic liver disease plays an important role in development of type I allergic skin manifestations. This effect has a direct mechanism through alcohol itself, and an indirect through elevation of IgE. Alcohol in liver disease and not liver disease causes immunologic abnormalities and accounts significantly for increased appearance of allergic skin reactions regardless of the extent of underlying liver disease.

Adult↗

Effect of prenatal alcohol exposure on neonatal sleep-wake behaviour and adult alcohol consumption in the AA and ANA rat lines.

To study the role of genetic factors in the effects of prenatal alcohol exposure on behaviour, dams of two rat lines developed to differ in voluntary alcohol intake, alcohol-preferring (AA) and alcohol-avoiding (ANA) rats were given a 5-10% alcohol solution mixed with a 1% sucrose solution as a sole drinking liquid throughout gestation. Sleep-wake behaviour of the offspring was studied at the ages of 7, 14 and 20 days, using a movement-sensitive mattress. In ANA rats, sleep recordings showed that prenatal alcohol exposure increased the percentage of waking but decreased the percentage of active sleep. Sleep-wake behaviour of the AA rats was not affected by alcohol exposure in utero. Prenatal alcohol exposure did not change open field behaviour in 1 month old rats, except that the alcohol-exposed AA rats' defaecation was decreased. When rats were 3 months old, voluntary intake of 10% (v/v) alcohol increased for alcohol-exposed ANA rats and decreased for alcohol-exposed AA rats as compared to the controls. The results indicate that AA rats may compensate for the effects of prenatal alcohol exposure on behaviour, whereas offspring of the alcohol-exposed ANA dams suffer from severe behavioural disturbances. These findings further suggest that genetic factors are responsible for the differences in the susceptibility of rat foetuses to alcohol-induced long-term effects on behaviour.

Alcohol Drinking↗

Carbohydrate-deficient transferrin as a marker of change in alcohol intake in men drinking 20 to 60 g of alcohol per day.

We evaluated carbohydrate-deficient transferrin (CDT) and gamma-glutamyltranspeptidase (gamma-GT) as markers of alcohol intake and change in alcohol intake in white Australian men aged 20 to 63 years who regularly drank 20 to 60 g of alcohol/day (2 to 6 standard drinks), either as weekend (n = 14) or daily drinkers (n = 41). After 4 weeks of familiarization on usual alcohol intake, men were provided with low alcohol beer (24 x 375 ml cans, 0.9%, v/v, two-weekly), and, for 4 weeks, consumed as much or as little as they wished with no additional alcohol permitted. In an alternate 4-week period, the same amount of full-strength beer (4.9%, v/v) was provided, whereas subjects continued their usual amount and pattern of alcohol consumption. The order of experimental conditions was randomized. Retrospective 7-day diaries documented weekly alcohol intake during 4 weeks of familiarization and 8 weeks of intervention. Mean alcohol intake was 345 g/week of alcohol (SD 97) during familiarization. During the last 4 weeks of intervention (study weeks 8 to 12), mean alcohol intake either increased by 360 g/week (SD 138) with the switch from low to high alcohol or decreased by 328 g/week (SD 120) with the reverse. During familiarization (study weeks 1 to 4), alcohol intake was significantly related independently (R2 = 0.21) to mean corpuscular volume (p = 0.008) and uric acid (p = 0.003), but not to gamma-GT (p = 0.22) nor CDT (p = 0.94). Change in alcohol intake was predicted independently (R2 = 0.60) by change in CDT (p < 0.0001) and gamma-GT (p = 0.0003), but not by change in uric acid or mean corpuscular volume. A 10% change in CDT gave 70% sensitivity and 80% specificity to detect a change of at least 2 standard drinks/day; respective values were 68% and 0 for 10% change in gamma-GT. Results were not related to drinking pattern, smoking, age, or weight. CDT, particularly when used as a continuous variable, may have a place in monitoring alcohol consumption, even in men whose alcohol intake is in the 20 to 60 g/day range.

Adult↗

Activation of prefrontal cortex and anterior thalamus in alcoholic subjects on exposure to alcohol-specific cues.

BACKGROUND: Functional imaging studies have recently demonstrated that specific brain regions become active in cocaine addicts when they are exposed to cocaine stimuli. To test whether there are regional brain activity differences during alcohol cue exposure between alcoholic subjects and social drinkers, we designed a functional magnetic resonance imaging (fMRI) protocol involving alcohol-specific cues. METHODS: Ten non-treatment-seeking adult alcoholic subjects (2 women) (mean [SD] age, 29.9 [9.9] years) as well as 10 healthy social drinking controls of similar age (2 women) (mean [SD] age, 29.4 [8.9] years) were recruited, screened, and scanned. In the 1.5-T magnetic resonance imaging scanner, subjects were serially rated for alcohol craving before and after a sip of alcohol, and after a 9-minute randomized presentation of pictures of alcoholic beverages, control nonalcoholic beverages, and 2 different visual control tasks. During picture presentation, changes in regional brain activity were measured with the blood oxygen level-dependent technique. RESULTS: Alcoholic subjects, compared with the social drinking subjects, reported higher overall craving ratings for alcohol. After a sip of alcohol, while viewing alcohol cues compared with viewing other beverage cues, only the alcoholic subjects had increased activity in the left dorsolateral prefrontal cortex and the anterior thalamus. The social drinkers exhibited specific activation only while viewing the control beverage pictures. CONCLUSIONS: When exposed to alcohol cues, alcoholic subjects have increased brain activity in the prefrontal cortex and anterior thalamus-brain regions associated with emotion regulation, attention, and appetitive behavior.

Alcohol Drinking↗

Pharmacogenetics of alcohol metabolism and alcoholism.

The pharmacogenetic differences among individuals in their capacity to metabolize ingested alcohol are possibly responsible for the large inter-individual and inter-ethnic variations observed in the outcome of alcohol use and misuse. Based on results of adoption, twin, and family studies it is now widely accepted that the vulnerability to alcoholism is determined by genetic factors as well as by environment. There is a constant search for biological markers and specific genes which could identify individuals genetically predisposed to alcohol abuse and alcoholism. Numerous 'candidate genes' for alcoholism have been suggested including the alcohol metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Both ADH and ALDH exhibit genetic heterogeneity. An atypical form of ADH (ADH2), which contains a variant beta 2 subunit instead of the usual beta 1 subunit, differs substantially from the usual form in its kinetic properties and is found more frequently among the Japanese, Chinese and other Mongoloid populations than in Caucasoids and Negroids. A widely prevalent genetic polymorphism has been observed for ALDH; about 50% of Japanese and Chinese livers possess an inactive ALDH (ALDH2 isozyme) whereas none of the Caucasian or Negroid populations show this isozyme abnormality. These metabolic polymorphisms seem to contribute to differences in the in vivo elimination rate of ethanol and acetaldehyde, and may explain differences in alcohol-related behaviour and its disease outcome. Taken together, Orientals who possess an atypical ALDH2 gene are more sensitive to acute responses to alcohol, tend to be discouraged from drinking alcohol, and consequently are at lower risk of developing alcohol-related disorders. However, more work is needed to support these findings. Recent advances in molecular genetics have made it possible to analyze directly the human genome. This may help in a better understanding of the complex genetic and environmental factors in alcohol abuse by providing prospects for identification of gene loci which may be responsible for predisposition to, and protection from, alcoholism.

Alcohol Dehydrogenase↗

The effect of tryptophan depletion on alcohol self-administration in non-treatment-seeking alcoholic individuals.

BACKGROUND: Alcohol self-administration in the laboratory has been used to evaluate pharmacological treatments and neurobiological mechanisms that underlie alcohol use in alcohol-dependent individuals. This study evaluated whether attenuation of serotonin synthesis via depletion of its precursor tryptophan reduces the amount of alcohol consumed in a self-administration paradigm in non-treatment-seeking individuals with alcohol use disorders. METHODS: Individuals with alcohol dependence (n = 8) and alcohol abuse (n = 4) who were not seeking treatment were recruited by advertisement and participated in two test days, 1 week apart. Each test session was preceded by administration of a concentrated amino acid drink that resulted in a rapid and significant decline in plasma free tryptophan (active depletion) or a similar drink containing tryptophan (placebo depletion). Tests were conducted in a randomized, double-blind fashion. The test session began with a cue exposure session where subjects were exposed to their favorite alcoholic beverage and asked to rate their craving for alcohol. After this, subjects were administered a priming drink designed to raise blood alcohol levels to 0.02 g%. Subjects then had the opportunity to drink up to eight additional drinks, each designed to raise blood alcohol levels by 0.02 g%, or to receive $3 for each drink not consumed over a 2-hr period. RESULTS: There were no significant differences in alcohol consumed or subjective intoxication with active tryptophan depletion compared with placebo. Self-reported craving correlated with the amount of alcohol consumed in the session. CONCLUSIONS: These data question the dependence of alcohol self-administration on the ongoing synthesis of serotonin.

Adolescent↗

Incidence of alcoholic pancreatitis in Japanese alcoholics: survey of male sobriety association members in Japan.

OBJECTIVE: To estimate the incidence of alcoholic pancreatitis, a dependence questionnaire survey was administered to male members of the sobriety association in Japan. METHODS: Questionnaires asking about age, age at start of alcohol drinking, amount of alcohol consumption, duration of drinking, the initiated age of abstinence, medical history of pancreatitis, the age at diagnosis of pancreatitis, and the etiology of pancreatitis were sent to 7876 male members of a sobriety association in Japan. RESULTS: Of 4120 members who replied to the questionnaire, 857 (20.8%) had a medical history of pancreatitis. Of these 857 members, 418 (10.1%) had been diagnosed with alcoholic pancreatitis, 32 (0.8%) as gallstone pancreatitis, and 407 (9.9%) with unknown etiology or etiology forgotten. A clear history of pancreatitis and information on habitual heavy drinking and the consumed amount of alcohol could be obtained from 373 of the 418 members diagnosed with alcoholic pancreatitis and from 345 of the 407 members with pancreatitis of unknown etiology. These 718 respondents were considered to be true alcoholic pancreatitis cases, with an extrapolated incidence of 9.1% (718/7876) to 17.4% (718/4120) cases of alcoholic pancreatitis in alcoholics in Japan. Alcoholics with a history of pancreatitis began drinking at relatively younger age and consumed a significantly greater amount of alcohol per day compared with 3113 alcoholics without a medical history of pancreatitis. CONCLUSION: This survey suggests that the incidence of alcoholic pancreatitis in alcoholics is much higher than previously reported.

Adult↗

Alcohol-predictive cues enhance tolerance to and precipitate "craving" for alcohol in social drinkers.

This study attempts to show that tolerance to alcohol is in large part a "learned" response, precipitated by contextual cues predictive of the unconditional drug effect. It also aims to show that the contextual cues integral to such "environment-dependent" tolerance function to increase motivational desire to drink alcohol. Male students (N = 40), drinking on average 10-20 units of alcohol per week, were randomly assigned to one of four groups. Two groups ingested 1.2ml/kg alcohol: one (AL-EXPT) with exteroceptive contextual cues typically associated with alcohol use, and the other (AL-UNEXPT) in a context not normally associated with alcohol. A third group (placebo) believed that they were drinking alcohol but, in fact, consumed a nonalcoholic beverage in the alcohol-expected context. The fourth group drank juice in the alcohol-unexpected context. As predicted, tolerance to the deleterious effects of alcohol on cognition and motor-performance, and subjective desire to consume alcohol, were influenced by the alcohol-predictive contextual cues. A physiological index (pulse rate) also tended to confirm that these cues elicited a conditioned compensatory response to alcohol. The implications of these findings for tolerance to and motivation to drink alcohol in a nonpathological population are discussed.

Adult↗

[Evaluation of an increased blood level of GGT, CDT, methanol, acetone and isopropanol in alcohol intoxicated automobile drivers. Alcoholism indicators instead of medical-psychological examination].

Several thousand blood samples were taken from alcoholized drivers at the Blood Alcohol Examination Centre of the Institute of legal Medicine at Cologne University. These samples showed blood alcohol contents (BAC) as well as GGT, CDT, methanol, acetone and isopropanol levels which indicated alcohol addiction. The blood samples were selected by the drivers' ages and their BAC, but in some cases the GGT also played a role. In the majority of cases 1 or 2 parameters were measured. In 200 cases all four indicators were determined. The four parameters characterize a different problematic drinking behaviour. GGT characterizes chronic, long-term misuse, CDT characterizes occasional misuse, methanol characterizes current addicted drinking and acetone and isopropanol characterize metabolic disorders caused by alcohol. The importance of parameters is thoroughly discussed, also in relation to incorrectly measured positive values and the relation between alcohol consumption and -problems. Methanol values above 10 mg/kg, GGT activities above 100 U/l and CDT levels above 60 U/l provide sufficient proof of there being an alcohol problem which requires treatment. The levels of other indicators need not be above normal to determine this. The proportion of drivers under the influence of alcohol with problematic alcohol levels increases significantly when the BAC is above 2.0 per mille. However, there have been drivers with alcohol problems with lower BAC levels. DUI offenders addicted to alcohol are quite frequently over 40 years old. A correlation between the single indicators and the BAC is rarely found. If a correlation is to be found, it would be most likely with drivers whose BAC lies above 2.0 per mille. The mentioned indicators would detect an alcohol problem from the blood sample taken for the blood alcohol test. Alcohol problems may be detected and treated shortly after the DUI offence. This method is comparatively cheaper than medical-psychological-examinations as well as being based on objective and verifiable parameters.

1-Propanol↗

The effect of changes in alcohol consumption on mortality and admissions with alcohol-related diagnoses in Stockholm County--a time series analysis.

AIM: To study the effect of changes in per capita alcohol sales and indicators of alcoholism treatment on admissions to inpatient care and mortality for liver cirrhosis and alcoholism, alcohol intoxication and alcohol psychosis (AAA). DESIGN: Bivariate and multivariate time series analyses was conducted by applying the ARIMA-modelling technique. SETTING AND PARTICIPANTS: All analyses were conducted on quarterly data from Stockholm County 1980-94 with a population of 1.7 million people. MEASUREMENTS: Data on sales of alcohol and disulfiram/calcium carbimide were used as input variables. Inpatient data (from the Stockholm Inpatient Care Register) and mortality data (from the Cause of Death Register) on all cases with alcoholism, alcohol psychosis and alcohol intoxication (AAA) and liver cirrhosis as underlying or contributory diagnoses were used as output variables. FINDINGS: Alcohol sales affected the cirrhosis rate. For cirrhosis mortality, but not for cirrhosis admissions, the effect was not only direct but also distributed over time. Significant direct and time lag effects of alcohol sales on both AAA series and cirrhosis admissions were found only during earlier, shorter periods, e.g. 1980-90. All four output series showed significant effects of sales of disulfiram/calcium carbimide and were the only significant predictors for the two AAA endpoints for the whole study period. CONCLUSIONS: These results suggest that to reduce the rate of alcohol-related problems caused by socially deteriorated and severely alcohol-dependent subjects (i.e. AAA), reduction of overall consumption should be complemented by treatment of alcohol-dependent subjects.

Alcohol Drinking↗

Distinct patterns of chemokine expression are associated with leukocyte recruitment in alcoholic hepatitis and alcoholic cirrhosis.

Alcoholic liver disease is associated with three histologically distinct processes: steatosis (parenchymal fat accumulation), alcoholic hepatitis (characterized by parenchymal infiltration by neutrophil polymorphs), and alcoholic cirrhosis (in which chronic inflammation and fibrosis dominate). Chemokines are cytokines that promote subset-specific leukoycte recruitment to tissues and could therefore play a crucial role in determining which leukocyte subsets are recruited to the liver in alcoholic liver disease. This paper reports that chemokine expression is increased in the liver of patients with alcoholic liver disease and, moreover, that distinct patterns of chemokine expression are associated with the different inflammatory responses to alcohol. Interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1 alpha), and MIP-1 beta were all detected in the parenchyma at sites of inflammation in alcoholic hepatitis, whereas in alcoholic cirrhosis, chemokines were restricted to inflammatory cells and endothelium in the fibrous septa and portal tracts. In alcoholic hepatitis, chemokine transcription was localized to sinusoidal cells, leukocytes, and fibroblasts in areas of parenchymal inflammation, but hepatocytes, despite staining strongly for chemokine protein, were negative. In alcoholic cirrhosis, chemokine mRNA was detected in portal tract endothelium, leukocytes, and fibroblasts. Thus, alcoholic hepatitis and alcoholic cirrhosis are associated with distinct patterns of chemokine expression that are likely to be important factors in determining whether a patient develops acute parenchymal inflammation and alcoholic hepatitis, or chronic septal inflammation and alcoholic cirrhosis.

Chemokine CCL2↗