Disulfiram, cocaine, and alcohol: two outcomes for the price of one?

The concurrent abuse of cocaine and alcohol is a common phenomenon,and is increasingly recognized as a difficult clinical issue.Several effective pharmacotherapies for substance dependencedisorders have been identified, though the search for an effectivepharmacotherapy for cocaine dependence has proved difficult.However, it has been suggested that disulfiram may offer a promisingtreatment option. The randomized, placebo-controlled study of Carroll et al. (2004)provides some of the strongest evidence to date regarding theeffectiveness of disulfiram treatment in reducing cocaine use.In a large     

Determination of ethyl glucuronide in hair samples

Ethyl glucuronide (EtG) is a non-volatile, water-soluble, stable-upon-storage,direct metabolite of ethanol and can be detected in body fluidsand tissues (and also in post-mortem material) for an extendedtime period after the complete elimination of alcohol from thebody (Alt et al., 1997; Schmitt et al., 1997; Seidl et al.,1998; Wurst et al., 1999a,b). The aim of the present Letteris to emphasize . . . [Full Text of this Article]FOOTNOTESREFERENCES     

Alcohol and hypertension: an old relationship revisited

The American comedian Henny Youngman (1906–1998) oncesaid, ‘When I read about the evils of drinking, I gaveup reading.’ Ironic, but interestingly as though witha sense of foresight, he did not speak of giving up drinking!It is despite the fact that alcohol is responsible for increasedillness, being causally related to more than 60 different medicalconditions (Rehm et al., 2003). Around 4% of the global diseaseburden is also thought to be alcohol related, which is comparablewith that attributed to the effects of tobacco (4.1%) and highblood pressure (4.4%) (Ezzati et al., 2002; WHO, 2002). For most diseases related to alcohol consumption, a dose–responserelationship exists with risk of the disease increasing withgreater amounts of alcohol intake, with cardiovascular     

Separate and Joint Effects of Alcohol and Smoking on the Risks of Cirrhosis and Gallbladder Disease in Middle-aged Women

The separate and joint effects of alcohol and smoking on incidencesof liver cirrhosis and gallbladder disease were examined ina prospective study of 1,290,413 United Kingdom women (meanage, 56 years) recruited during 1996–2001. After a meanfollow-up of 6.1 years (1996–2005), incidence rates ofcirrhosis and gallbladder disease were 1.3 per 1,000 persons(n = 2,105) and 15 per 1,000 persons (n = 23,989), respectively,over 5 years. Cirrhosis risk increased with increasing alcoholconsumption, while the risk of gallbladder disease decreased(P_trend < 0.0001 for each). Comparing women who drank 15units/week with those who drank 1–2 units/week, the relativerisk was 4.32 (95% confidence interval (CI): 3.71, 5.03)) forcirrhosis and 0.59 (95% CI: 0.55, 0.64) for gallbladder disease.Increasing numbers of cigarettes smoked daily increased therisk of both conditions (P_trend < 0.0001 for each). Comparingcurrent smokers of 20 cigarettes/day with never smokers, therelative risk was 3.76 (95% CI: 3.25, 4.34) for cirrhosis and1.29 (95% CI: 1.22, 1.37) for gallbladder disease. Effects ofalcohol and smoking were more than multiplicative for cirrhosis(P_interaction = 0.02) but not for gallbladder disease (P_interaction= 0.4). Findings indicate that alcohol and smoking affect therisks of the 2 conditions in different ways. For cirrhosis,alcohol and smoking separately increase risk, and their jointeffects are particularly hazardous. For gallbladder disease,alcohol reduces risk and smoking results in a small risk increase. alcohol drinking; gallbladder diseases; liver cirrhosis; liver diseases, alcoholic; prospective studies; smoking     

Detection times for urinary ethyl glucuronide and ethyl sulfate in heavy drinkers during alcohol detoxification

Aims: Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are conjugatedethanol metabolites formed in low amounts after alcohol consumption.Compared with ethanol, EtG and EtS are excreted in urine fora prolonged time, making them useful as sensitive alcohol biomarkers.This study determined the detection times for EtG and EtS inalcoholic patients undergoing alcohol detoxification. Methods:Alcohol-dependent patients (n = 32) with an initial alcoholconcentration 1 g/L based on breath testing were followed duringdetoxification. Urine samples for determination of EtG, EtS,ethanol and creatinine were collected on admission to the hospitaland thereafter once daily for several days. EtG and EtS measurementswere performed by liquid chromatography-mass spectrometry (LC-MS)and EtG also using an immunochemical assay (DRI-EtG EIA, ThermoFisher/Microgenics).Results: The detection time for urinary EtG was weakly correlated(r = 0.434, P = 0.013) with the initial alcohol concentration(range 1.0–3.4 g/L). For EtG, the individual time rangeuntil return to below the applied cut-off limit (<0.5 mg/L)was 40–130 h (median 78) with a similar time course observedfor EtS. After correction for urine dilution, the time untilan EtG/creatinine ratio <0.5 mg/g was 40– 90 h (median65). The detection times after an estimated zero ethanol concentrationwere 30–110 h (median 66) for EtG and 30– 70 h (median56) for EtG/creatinine. The EtG results by LC-MS and the immunoassaywere in good agreement. Conclusions: During alcohol detoxification,EtG and EtS remained detectable in urine for several days. Thedetection times showed wide inter-individual variations, alsoafter adjusting values for urine dilution and to the estimatedtimes for a completed ethanol elimination.     

Intravenous injection of alcohol by drug injectors: report of three cases

The injection of psychoactive drugs, usually by the intravenousroute, has been recognized for more than a century, and hasbecome more widespread over recent decades (Golding, 1993; Derricotet al., 1999). We have been unable to identify any publishedexamples of the recreational injection of alcohol. We describehere three cases in which intravenous injection of alcohol isreported. Case 1 was a 29-year-old, single, unemployed and homeless man,admitted to hospital for alcohol and diazepam detoxification.He fulfilled ICD-10 criteria . . . [Full Text of this Article]FOOTNOTESREFERENCES     

The volume of the liver in patients correlates to body weight and alcohol consumption

The measurement of liver volume has gained practical use inrelation to liver transplantation (Kawasaki et al., 1993). Livervolume may also relate to the many metabolic processes in whichthe liver is engaged (Homeida et al., 1979; Marchesini et al.,1988; Murry et al., 1995; Reichel et al., 1997; Kwo et al.,1998; Andersen et al., 1999). The present study was undertakento measure liver . . . [Full Text of this Article]FOOTNOTESREFERENCES     

Is daily single dosage of diazepam as effective as chlordiazepoxide in divided doses in alcohol withdrawal--a pilot study

We report on a pilot double-blind study on the effectivenessof divided doses of chlordiazepoxide and a single daily doseof diazepam in the treatment of the alcohol-withdrawal syndrome.While a variety of drugs (chlormethiazole, propranolol and clonidine)have been used for treatment of alcohol-withdrawal symptoms,benzodiazepines remain the drugs of choice for alcohol detoxification(Mayo-Smith, 1997). Diazepam and chlordiazepoxide are both . . . [Full Text of this Article]APPENDIXFOOTNOTESREFERENCES     

Gamma-hydroxybutyrate (GHB)-deficiency in alcohol-dependence?

I wish to propose a hypothesis that could help explain someof the effects of baclofen in alcohol dependence that are describedin Dr. Bucknam's case study (Bucknam, 2007) and in my self-casereport (Ameisen, 2005). At a behavioural     

EFFECTS OF VARIOUS CYTOCHROME P-450 INDUCERS ON TESTOSTERONE METABOLISM AND SEVERAL MONOOXYGENASE ACTIVITIES IN SPRAGUEDAWLEY (SpD), HIGH ALCOHOL SENSITIVITY (HAS) AND LOW ALCOHOL SENSITIVITY (LAS) RATS

Hydroxylation of testosterone (TST) has been shown to be regio-and stereo-specific for a number of cytochrome P-450 isoenzymes.Three rat lines [Sprague-Dawley (SpD), high alcohol sensitivity(HAS) and low alcohol sensitivity (LAS)] were tested for thisenzymatic specificity after treatment with phenobarbital, clofibrate,3-methylcholanthrene and pregnenolone-16-carbonitrile. Thesecompounds are known to induce cytochrome P-450 2B, 4A, 1A and3A1. respectively, in the rat. Induction efficiency was establishedby using the usual enzyme activities specific for these P-450s(pentoxyresorufin, lauric acid, ethoxyresorufin and nifedipineoxidase). Five mono hydroxylated TST metabolites were separatedusing a sensitive HPLC procedure. The hydroxylation of TST wasfound to be significantly different between the lines even inthe uninduced state. The formation of the metabolites of TST,hydroxylated on 2 or 7 or 16 positions and oxidated on carbon17 (4), was found to be significantly increased in SpD ratswhen compared with the HAS-LAS lines (P < 0.0001 in eachcase). When the HAS-LAS lines were compared, the quantity of2 and 16 hydroxylated metabolites was found to be significantlylower in LAS rats (P < 0.05). These differences persisted,although in the opposite direction, after 3-methylcholanthrene(P < 0.01 for both 2 and 16) and phenobarbital induction(P < 0.01 for 2). In conclusion, large differences in TSThydroxylation were found between the SpD and HAS-LAS rats whilemore subtle differences were found between the more closelyrelated HAS-LAS lines especially after phenobarbital and 3-methylcholanthreneadministration as confirmed by our enzyme activity results.The above differences in steroid metabolism between HAS andLAS rats may help to explain their contrasting sensitivitiesto alcohol.     

PREVALENCE AND CORRELATES OF DSM-IV AND ICD-10 ALCOHOL DEPENDENCE: 1990 US NATIONAL ALCOHOL SURVEY

This paper describes DSM-IV and ICD-10 alcohol dependence prevalencerates and sociodemographic and drinking correlates. The sampleunder analysis (n = 2058) constitutes a multicluster probabilitysample of the US adult household population. The study responserate is 71%. The prevalence rate for current (past 12 month)DSM-IV alcohol dependence is 3.9%, and for current ICD-10 itis 5.5%. Agreement between DSM-IV and ICD-10 on whether respondentsare dependent or not is less than optimal (Kappa = 0.67). Thepredictors of ICD-10 alcohol dependence are the frequency ofdrinking five or more drinks on occasion and age (inverse relationship).For DSM-IV alcohol dependence the correlates are drinking fiveor more drinks on occasion, being unemployed and age (also aninverse relationship). Differences in results underline theimportance of understanding the variations among DSM-IV andICD-10 criteria for alcohol dependence and the implicationsof these differences for epidemiological research. The highprevalence of dependence among young men may be the result ofrecognizing consequences of episodic heavy drinking as signsof alcohol dependence.     

INCREASED SERUM ACETATE AS A MARKER OF PROBLEM DRINKING AMONG DRUNKEN DRIVERS

727 consecutive drunken drivers were studied for laboratorymarkers of excessive alcohol consumption. Serum -glutamyltransferaseand alanine aminotransferase showed no differences and aspartateaminotransferase and blood alcohol concentration only smalldifferences between groups of first and repeating drunk drivingoffenders. The best laboratory test to differentiate the repeatingoffenders with probably more serious alcohol problems from thefirst offenders was in our material serum acetate, the meanserum acetate level of the repeating offenders being highlysignificantly (P<0.001) higher than that of the first offendersor nonalcoholic controls. Serum acetate also differentiatedfirst offenders from nonalcoholic controls (P<0.001). Ourresults suggest that serum acetate could be used for the screeningof problem drinking among drunken drivers.     

Adverse Childhood Events and Lifetime Alcohol Dependence

Objectives. We sought to study the association between adverse events occurring in childhood and adolescence and lifetime alcohol dependence in a representative sample of American adults.Methods. With data from the National Epidemiologic Survey on Alcohol and Related Conditions, we conducted logistic regression multivariate analyses to examine the impact of adverse events occurring in childhood (aged < 18 years) on the lifetime prevalence of alcohol dependence. We controlled for age at drinking onset, binge drinking, alcoholism in parents and grandparents of respondents, and demographic characteristics.Results. Adverse childhood events were associated with familial alcoholism and with early and binge drinking, and therefore, we controlled for these potential confounders. Experiencing 2 or more adverse childhood events, compared with none, significantly increased the risk for alcohol dependence, even after we controlled for sociodemographic variables and disorder-specific potential confounders not considered in the extant literature (adjusted odds ratio = 1.37; 95% confidence interval = 1.06, 1.77).Conclusions. Individuals who experienced 2 or more adverse childhood events are at increased risk for lifetime alcohol dependence. A better understanding of the factors underlying the risk for alcohol dependence is important for developing better prevention and early intervention measures.Alcohol dependence is a major public health problem. National findings indicate that nearly an eighth of Americans (12.5%) met criteria at some point in their lives for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV),¹ alcohol dependence² and that alcohol dependence is associated with significant disability and with poor mental health.³ A better understanding of the factors underlying the risk for alcohol dependence is important for developing better prevention and early intervention measures.Research in treated and untreated populations consistently shows that adverse childhood events (i.e., events occurring before the child is aged 18 years) predict alcohol dependence.^2,4–6 Data from a survey conducted in the early 1990s suggested that several adverse events increased the risk for alcohol dependence after sociodemographic variables were controlled for, and the joint effect of exposure to multiple adverse events was stronger than the effect of a single adverse event.² A questionnaire survey of health maintenance organization (HMO) members suggested a linear relationship between the number of adverse childhood events and the probability of responding positively to single questions on having an alcohol problem or considering oneself alcoholic.⁵ For example, compared with those not reporting any adverse childhood events, individuals reporting 1 and 2 adverse childhood events were 2 and 4 times more likely, respectively, to consider themselves alcoholics. These studies suggest that the number of adverse childhood events is a more powerful predictor of adult alcohol-use disorders than any specific adverse childhood event.The cumulative stress associated with experiencing several adverse childhood events has been associated with increased risk for negative mental health outcomes⁷ and might explain the increased propensity to use alcohol and eventually become alcohol dependent, perhaps seeking relief from the enduring impact of these events. Even though adverse childhood events have been shown to be associated with alcohol dependence, information is lacking on whether this association remains significant after one controls for other known strong risk factors that may confound the association.Three such strong risk factors arise from an extensive literature. First, familial alcoholism is a strong risk factor for alcohol dependence.^8–10 Second, early drinking onset predicts alcohol dependence in both cross-sectional and prospective studies,^11,12 and twin studies suggest that the association is because of familial sources, reflecting shared environmental and genetic factors¹² and unique environmental factors.¹¹ Third, binge drinking is associated with the onset and chronicity of alcohol dependence in cross-sectional¹³ and prospective studies.^14–16 Whether the association between adverse childhood events and lifetime alcohol dependence remains significant after one controls for these strong risk factors is unknown.We addressed this question with data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a large, nationally representative survey of American adults that includes information about adverse childhood events, age at drinking onset, binge drinking, and alcoholism in parents and grandparents of respondents. The NESARC data provide a uniquely advantageous opportunity to study the impact of adverse childhood events on alcohol dependence among adults. We hypothesized that adverse childhood events would be significantly associated with lifetime alcohol dependence and that the magnitude of this association would remain significant after we controlled for alcoholism in the 2 preceding generations and for binge and early drinking.     

BEHAVIORAL THERMOREGULATION IN THE RAT FOLLOWING THE ORAL ADMINISTRATION OF ETHANOL

To assess if ethyl alcohol (ethanol) causes a reduction in theset-point for control of body temperature, behavioral thermoregulatoryresponses in the Fischer rat were measured following a singleoral administration of ethanol. In a preliminary study, fiverats were given 3.0 g/kg ethanol dissolved in saline (20%; v/v)by gavage and placed in a longitudinal temperature gradientfor 2 hr. The temperature gradient permitted the rats to behaviorallythermoregulate (i.e. select a thermal preferendum). The selectedambient temperature (T) in the temperature gradient was notablylower during the initial and final stages of the test periodwhen compared to the response of rats administered similar volumesof saline. Colonic temperature upon removal from the gradientwas approximately 1.0°C below that of the saline-treatedanimals. In a followup study, rats were placed in the temperaturegradient for 1 hr for accommodation purposes. The rats werethen gavaged with 0,1.0 or 3.0 g/kg ethanol and placed backin the gradient for another 2 hr. Selected T was significantlyreduced in the 3.0 g/kg group during the second hour post-ethanolexposure. The 1.0 g/kg dosage had little effect on selectedT. As in the preliminary study, the colonic temperature of therats in the follow up study given 3.0 g/kg was 1.0°C belowthat of the control at 2 hr post-injection. Because the 3.0g/kg treated animals were significantly hypothermic and selectedcooler Ts in the temperature gradient, it was concluded thatethanol exerted a lowering of the set-point for control of bodytemperature.     

Alcohol exposure in utero and breast cancer risk later in life

Since the pioneering work of Hiatt and Bawol (1984), there hasamassed a considerable amount of evidence that moderate-to-heavyalcohol consumption increases risk of breast cancer in women(Willett et al., 1987; Longnecker, 1999). A plausible mechanismis by alcohol's effects on circulating hormone levels. Alcoholadministration has been reported to increase circulating oestradiollevels in pre-menopausal women (Reichman et al., 1993); theevidence is mixed in . . . [Full Text of this Article]FOOTNOTESREFERENCES     

Predictors of cardiovascular health knowledge among suburban cable TV subscribers and non-subscribers

This study focused on how social-psychological and demographicfactors combined to predict information-holding about cardiovasculardisease prevention among subscribers and non-subscribers toa suburban Midwest cable television system. Data come from oneof three education communities of the Minnesota Heart HealthProgram, a research and demonstration project to reduce communitylevels of heart attack and stroke. A principal component factoranalysis of the total sample (N = 635) extracted two factorsfrom variables operationalizing involvement, self-efficacy andsalience: ‘orientation to health behavior change’,and ‘orientation to disease consequences’. Separatefactor analyses for non-subscribers (N = 228) and subscribers(N = 407) showed a similar factor structure for the former,but the addition of a ‘transitional orientation’factor for the latter characterized by less orientation to healthbehavior change, but greater awareness of increasing informationabout heart disease prevention. These factors together withvariables of gender, age, education, occupation, family compositionand television use were entered into multiple regression analysesfor the total sample (P 0.001), and separately for subscribers(P 0.01) and non-subscribers (P 0.01). In general, gender,education and age emerged as significant predictors with healthorientation and television exposure marginally predictive amongcable-subscribers only.     

Prevalence of asthma in schoolchildren under-represents those from socially deprived areas

We were interested to read the excellent study by McCann etal. in the February edition of Health Education Research (McCannet al., 2002). We have recently conducted a similar, but smaller,study that sheds some light upon their results. Our study aimedto assess the impact of our local asthma health promotion schemefor schools [Asthma Friendly Schools (AFS) Initiative], whichhad been in place for 5 years and had been adopted by abouthalf of all Portsmouth schools. We     

BMI, lipid profile, physical fitness and smoking habits of young male adults and the association with parental education

Background: Few studies have focused on the potential relationshipbetween parental educational level and cardiovascular risk factorsamong young male adults. The aim of this study was to investigatecardiovascular disease risk factors among young men and whetherbody mass index (BMI), serum lipids, physical fitness and smokinghabits were related to paternal and maternal education. Methods: In this cross-sectional study 750 18- to 26-year-oldmale recruits participated. Results: Linear regression analyses showed that the paternaleducation was inversely associated with BMI (P = 0.035) andthe concentration of total cholesterol (P = 0.003) and low-densitylipoprotein (LDL) (P = 0.014). Running performance was inverselyrelated to cigarette smoking (P = 0.022) and the concentrationof triacylglycerol (P = 0.001). BMI was positively related tothe concentration of LDL (P = 0.002), total cholesterol/high-densitylipoprotein (HDL) ratio (P < 0.001) and inversely relatedto the concentration of HDL (P < 0.001), running performance(P < 0.001) and muscular strength (P = 0.011). Recruits withlow BMI, both high and low fitness, had a significantly betterlipid profile than recruits with high BMI and low fitness (P 0.016). A lower concentration of triacylglycerol (P 0.001)and a higher concentration of HDL (P = 0.034) were further shownamong recruits with high BMI/high fit compared to recruits withhigh BMI/low fit. Conclusions: High paternal educational level was associatedwith a lower BMI and a better lipid profile among young adultmen. Furthermore, men with low BMI, both high and low fit, hada better lipid profile than those with high BMI/low fit. Menwith high BMI/high fit had a better lipid profile that thosewith high BMI/low fit.     

META-ANALYSIS OF THE EFFECTS OF ALCOHOL DEHYDROGENASE GENOTYPE ON ALCOHOL DEPENDENCE AND ALCOHOLIC LIVER DISEASE

The purpose of this paper is to assemble and evaluate existingdata on the effect of genetic variation in ADH2 and ADH3 onthe risk of alcohol dependence, and on the risk of alcoholicliver disease. Calculations of odds ratios and their confidencelinuts, and tests for heterogeneity of the results from theavailable studies, have been performed. It is clear that possessionof the ADH2-2 allele decreases the risk of alcohol dependence,but it increases the risk of alcoholic liver disease among alcoholics.ADH3 variation also has significant effects on alcohol dependence,which may be due to linkage to ADH2; the ADH3 effect differssignificantly between Asian and European subjects. ThereforeADH genotype has substantial effects on risk of alcohol dependenceand alcoholic liver disease, but more work is needed on thegeneralizability of these findings to non-Asian populations,and on possible mechanisms.     

Double jeopardy--drug and sex risks among Russian women who inject drugs: initial feasibility and efficacy results of a small randomized controlled trial

Background

Alcohol problems are a major health issue in Nepal and remain under diagnosed. Increase in consumption are due to many factors, including advertising, pricing and availability, but accurate information is lacking on the prevalence of current alcohol use disorders. The AUDIT (Alcohol Use Disorder Identification Test) questionnaire developed by WHO identifies individuals along the full spectrum of alcohol misuse and hence provides an opportunity for early intervention in non-specialty settings. This study aims to validate a Nepali version of AUDIT among patients attending a university hospital and assess the prevalence of alcohol use disorders along the full spectrum of alcohol misuse.

Methods

This cross-sectional study was conducted in patients attending the medicine out-patient department of a university hospital. DSM-IV diagnostic categories (alcohol abuse and alcohol dependence) were used as the gold standard to calculate the diagnostic parameters of the AUDIT. Hazardous drinking was defined as self reported consumption of ≥21 standard drink units per week for males and ≥14 standard drink units per week for females.

Results

A total of 1068 individuals successfully completed the study. According to DSM-IV, drinkers were classified as follows: No alcohol problem (n=562; 59.5%), alcohol abusers (n= 78; 8.3%) and alcohol dependent (n=304; 32.2%). The prevalence of hazardous drinker was 67.1%. The Nepali version of AUDIT is a reliable and valid screening tool to identify individuals with alcohol use disorders in the Nepalese population. AUDIT showed a good capacity to discriminate dependent patients (with AUDIT ≥11 for both the gender) and hazardous drinkers (with AUDIT ≥5 for males and ≥4 for females). For alcohol dependence/abuse the cut off values was ≥9 for both males and females.

Conclusion

The AUDIT questionnaire is a good screening instrument for detecting alcohol use disorders in patients attending a university hospital. This study also reveals a very high prevalence of alcohol use disorders in Nepal.