The A1 allele of the D2 dopamine receptor gene is associated with high dopamine transporter density in detoxified alcoholics

The A1 allele of TaqI A restriction fragment length polymorphism(RFLP) in the D₂ receptor (DRD₂) gene locus has been suggestedto be associated with low D₂ receptor density in man. Striataldopamine transporter (DAT) densities were studied with [¹²³I]2-ß-carbometoxy-3ß(4-iodophenyl)tropaneand single-photon emission tomography in 29 detoxified alcoholics,who were also genotyped for the two alleles of TaqI A RFLP atthe DRD2 receptor gene locus. Alcoholics with the A1/A2 genotypes(n = 10) had statistically significantly higher DAT densitiesthan subjects with the A2/A2 genotypes [n = 19; 8.0 ±1.2 (mean ± SD) vs 6.9 ± 1.1, P = 0.035]. We suggestthat the TaqI A RFLP is in linkage disequilibrium with a genevariant modifying DAT density in alcoholics.     

5-HT1A Receptors in the Frontal Cortical Brain Areas in Cloninger Type 1 and 2 Alcoholics Measured by Whole-Hemisphere Autoradiography

Aims: The Cloninger type 1 alcoholics are prone to anxiety,and in many cases patients have begun to use alcohol in orderto relieve their anxiety. We have previously reported a decreaseof the serotonin transporter density in the perigenual anteriorcingulate cortex (pACC) in type 1 alcoholics. The 5-HT_1A receptorsare the binding sites for anxiolytic drug buspirone. We aimedto investigate the alteration in the density of 5-HT_1A receptors,that may also alter the effect of serotonin in the pACC in alcoholics.Methods: The density of the serotonin receptor 5-HT_1A amongCloninger type 1 and 2 alcoholics (nine and eight subjects,respectively) and 10 control subjects were determined by postmortemwhole-hemisphere autoradiography with WAY-100635. Results: Substantiallysparser 5-HT_1A (by –31%, P = 0.010) density was observedin the pACC of alcoholic subjects in relation to non-alcoholiccomparison subjects. In a secondary analysis for the differencebetween the alcoholic subtypes and controls, the 5-HT_1A densitywas decreased significantly by –32% (P = 0.015) in theupper level of pACC in type 1 alcoholics. Conclusions: The detecteddecrease of 5-HT_1A receptor density on the pACC suggests furtherthat the serotoninergic system is defected in the so-calledaffect region, especially in the type 1 alcoholics.     

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     

Secondary depression in weaned alcoholics: implications of Lesch's typology of chronic alcoholism

Schuckit (1983) described two types of alcohol-related depression:(1) the common type, in which secondary depression disappearswithout treatment within the first few weeks of abstinence;(2) a less frequent type, primary depression, requiring specifictreatment. It is difficult to anticipate whether an alcoholicpatient needs antidepressive treatment or whether depressionwill remit spontaneously. A potential guide to differentiatedepressed alcoholic patients who might need specific treatmentfor depression could be the typology of Lesch et al. (1990).Based on . . . [Full Text of this Article]ConclusionFOOTNOTESREFERENCES     

Translation problems of the Spanish version of the Readiness to Change Questionnaire

The Readiness to Change Questionnaire instrument by Rollnicket al. (1992) has become a standard in assessing stages of changeamong substance users. It has found such widespread acceptancethat recently it has been translated into Spanish by Rodriguez-Martoset al. (2000). . . . [Full Text of this Article]FOOTNOTESREFERENCES     

Reversal of ethanol-induced hepatic steatosis and lipid peroxidation by taurine: a study in rats

We read with interest the study reported by Kerai et al. inthe July–August (1999) issue of Alcohol and Alcoholism.The authors concluded that hepatic steatosis and lipid peroxidationcaused by chronic alcohol consumption in rats can be reversedby administration of taurine. Furthermore, . . . [Full Text of this Article]FOOTNOTESREFERENCES     

D2 DOPAMINE RECEPTOR TaqI ALLELES IN MEDICALLY ILL ALCOHOLIC AND NONALCOHOLIC PATIENTS

The prevalence of TaqI A alleles of the D₂ dopamine receptor(DRD2) gene was examined in two subgroups of medically ill nonalcoholics(more prevalent and less prevalent substance users, MPSU andLPSU, respectively) and in two subgroups of medically ill alcoholics(more severe and less severe alcoholics, MSA and LSA, respectively).The prevalence of the Al allele in the 80 nonalcoholic and 73alcoholic patients was 30.0% and 52.1%, respectively (P = 0.009).In the four subgroups of these patients, the prevalence of thisallele was: LPSU = 18.2%, MPSU = 34.5%, LSA = 44.4% and MSA= 58.3%. Linear trend analysis showed that as the use of substancesand severity of alcoholism increase, so does Al prevalence (P= 0.001). Specific, subgroup comparisons showed Al prevalencein MSA to be about 3-fold (P = 0.007) and 1.5-fold (P = 0.04)higher than in LPSU and MPSU subgroups, respectively. Similarly,in a combined analysis of independent studies, Al prevalencein MSA was higher when compared to LSA (P < 5 x 10^–3),MPSU (P < l0^–4 and LPSU (P < l0^–8) subgroups.There was virtually no difference in the prevalence of the Alallele between LSA and MPSU subgroups. None of the specificmedical or neuropsychiatric complications of alcoholism wasassociated with the Al allele. In conclusion, the severity ofalcohol dependence in alcoholics and of substance use behaviorsin controls are important variables in DRD2 allelic association.The present report and converging lines of evidence suggestthat the DRD2 locus could represent a prominent gene risk factorfor susceptibility to severe alcoholism. However, other genesand environmental factors, when combined, still play the largerrole.     

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     

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     

ALCOHOLICS WITH REDUCED DOPAMINE D2 RECEPTOR FUNCTION POSSESS NORMAL PLATELET MONOAMINE OXIDASE ACTIVITY

Platelet monoamine oxidase (MAO) activity, proposed to be amarker for central 5- hydroxytryptamine (5-HT) capacity, wasinvestigated in 14 severely alcohol-dependent subjects withreduced dopamine (DA) D₂ receptor function, as assessed by thegrowth hormone responses to apomorphine. Twelve healthy menwere used as controls. Platelet MAO activity in the alcohol-dependent subjects was not different from that in controls.The finding from this preliminary study suggests that severelyalcohol-dependent subjects with reduced DA D₂ receptor functionhave normal 5-HT capacity.     

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     

The value of oral thiamine

Cook (2000) advocated parental replacement of thiamine as aroutine accompaniment to in-patient alcohol detoxification.The justification is . . . [Full Text of this Article]REFERENCES     

ON INTRACELLULAR FORMATION OF ETHANOL AND ITS POSSIBLE ROLE IN ENERGY METABOLISM

Despite a great number of papers devoted to studies of the influenceof alcohol on man's health, very few of them discuss the issueof the presence of ethanol in the human body not connected withalcohol consumption. Such ethanol is commonly called endogenous.It is believed to originate from the microbial fermentationof the carbohydrates in the gastro-intestinal tract (Krebs andPerkins, . . . [Full Text of this Article]REFERENCES     

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     

Introduction to personality-biological interactions in alcoholism: 'The Markku Linnoila Memorial Symposium'.

Although a number of specific personality disorders, includinganti-social personality, passive-dependent personality, andexplosive personality, have been associated with the diagnosisof alcoholism, studies of the relationship of underlying personalityand/or temperament to the nature, phenomenology, psychobiology,prognosis, and treatment of alcoholism have occurred much lessfrequently. However, there is a growing body of evidence thatcore or underlying personality and temperament are . . . [Full Text of this Article]FOOTNOTES     

PLASMA LIPIDS AND ALCOHOL CONSUMPTION IN ALCOHOLIC MEN: EFFECT OF WITHDRAWAL

This study examines the effect of alcohol withdrawal on plasmalipids and particularly on HDL-cholesterol subfractions, in18 middle-aged, clinically healthy but chronically drinkingmen, institutionalized for withdrawal therapy. Plasma lipids,total HDL and HDL₃-cholesterol, Apo A-I and Apo B were assayedbefore and after 30–86 days of abstinence. A 38% decreasein mean total HDL-cholesterol levels was observed after withdrawaltherapy (P = 0.0002), and this was due mainly to a drop in HDL₃-cholesterolconcentrations (–43%, P = 0.0002). The decrease in HDL₂-cholesterolconcentrations was also significant (–21%, P < 0.005)but less marked. These results were not dependent on quantitiesof alcohol ingested before therapy, on duration of hospitalizationand on changes in dietary fat intake or smoking habits. ApoA-I levels decreased (–39%, P = 0.0002) and the magnitudeof the decrease after alcohol withdrawal was positively relatedto the duration of hospitalization. Apo B levels increased (+24%,P < 0.005). Among the anthropometric parameters, arm musclearea was significantly higher after alcohol withdrawal. Theenergy and macronutrient intakes did not significantly changeduring hospitalization. It is concluded that the modificationsof HDL-cholesterol, HDL₃-cholestercol, HDL₂-cholesterol ApoA-I and Apo B values were induced by alcohol withdrawal in thispopulation of chronic French alcoholics.     

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     

REDUCED [3H]SCH 23390 BINDING AND DA-SENSITIVE ADENYLYL CYCLASE IN THE LIMBIC SYSTEM OF ETHANOL-PREFERRING RATS

Dopamine (DA) D₁ receptors and the response of adenylyl cyclase(AC) to dopamine stimulation were studied in the limbic areasand the caudate-putamen of Sardinian ethanol-preferring (SP),Sardinian ethanol-non-preferring (SNP) and Wistar unselected(UW) rats. SP rats exhibited a significantly lower number ofD₁ receptors, measured using [³H]SCH 23390 binding, and a decreasedresponse to DA stimulation than SNP and UW animals. Since SPrats have also a low number of D2 receptors, the results suggestthat an altered dopaminergic transmission may underlie theirinnate alcohol preference     

Effect of Helicobactor pylori eradication therapy on dyspeptic symptoms in primary care

OBJECTIVE: The aim was to explore the effect of eradication therapy ondyspeptic symptoms in patients with known peptic ulcer disease(PUD). METHOD: A total of 164 known dyspeptics and 147 non-dyspeptic attendersat six UK general practices were recruited. The Helisal RapidBlood test was performed in the practices and eradication therapyleft to the preference of the general practitioner. Patientswere followed prospectively by a Likert scaled symptom questionnaireand record review. The symptom questionnaire distinguished betweenpatients known to have dyspepsia and those not. RESULTS: There was a statistically significant decrease in dyspepticsymptoms in patients with known PUD who received eradicationtherapy (n = 43, Z = –2.63, P = 0.009). CONCLUSIONS: Eradication of Helicobacter pylori in primary care can leadto a reduction in consumption of H2 receptor antagonists andhence cost savings. This study demonstrates that dyspeptic symptomsalso decrease. The questionnaire could be used in further studiesto evaluate the effect of management on dyspeptic symptoms inthe primary care setting. Keywords. Dyspepsia, Helicobactor pylori, primary care, therapy, outcome measures.     

Effects of a 10-week exercise intervention programme on exercise and work capacities in Belfast's ambulancemen

The objective of the present study was to investigate the occupationalbenefits of an exercise intervention programme, including changesin physical working capacity and other physical fitness measureson a group of Belfast ambulancemen. Physical training was performedtwice weekly for 10 weeks and consisted primarily of indoorsoccer and circuit-training sessions. Both experimental (n=8)and control subjects (n=6) were assessed for height (HT), weight(WT), body composition (percentage fat), standing broad jump(SBJ), flexibility (Flex), and sit-up performance (SU). Theexperimental group was further assessed for blood pressure (BP),hand grip strength (HGS), maximal oxygen consumption ($$$O₂max), end lactate concentration (EL), anaerobic threshold (AT)and leg strength (LS). Working capacity was also assessed duringa staged emergency incident, using a portable telemetric gasanalyser. Significant changes in the experimental group werefound following training for Flex, SU, SBJ, $$$O₂ max (all P<0.05),EL and AT (P<0.01). A significant drop in the metabolic costof the simulated emergency incident was also noted followingtraining. No significant differences were found for the controlgroup over the experimental period. The present study indicatedthat a twice-weekly exercise intervention programme was effectivein improving the physical fitness of Belfast's ambulancemen.Such a programme could prove cost-effective by increasing workcapacity and decreasing absenteeism related to musculoskeletalinjury.