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Alcohol Related Birth Injury (FAS/FAE) Resource Site Health Care Professional Centre
Biomarker Abstracts
Title Biochemical markers of alcohol use and abuse: experiences from the Pilot Study of the WHO/ISBRA Collaborative Project on state and trait markers of alcohol. International Society for Biomedical Research on Alcoholism. Author Helander A; Tabakoff B Address Karolinska Institute, Department of Clinical Neuroscience, St Gorans Hospital, Stockholm, Sweden. Source Alcohol Alcohol, 1997 Mar, 32:2, 133-44 Abstract The development of reliable diagnostic tools for assessing alcoholism and harmful alcohol consumption is an utmost necessity for the success of efforts to prevent and treat alcohol-induced damage to both individuals and to society. A multinational study is underway to aid in the development of biological screening tools (state markers) which can, with good sensitivity and specificity, identify problem drinkers. To attain this goal information needs to be available on an individual's drinking history and habits and related factors. A detailed instrument has been developed to obtain this information. The second goal of the study was to begin to develop diagnostic 'trait markers' which provide biological information on genetically determined predisposing and protective factors in the development of alcoholism. The developed questionnaire also provides background information on subject characteristics necessary for the development of trait markers. Centres will assay the obtained biological samples for 'traditional' and newly identified state markers of excessive alcohol consumption. These will include methanol measurements, gamma-glutamyltransferase, aspartate aminotransferase, carbohydrate-deficient transferrin, serotonin metabolite ratios, and erythrocyte aldehyde dehydrogenase. DNA obtained from the lymphocytes of subjects will be assayed for polymorphisms of alcohol- and aldehyde-metabolizing enzymes and dopamine receptor polymorphisms which can provide insights into protective and predisposing factors in alcoholism. The platelet enzymes, monoamine oxidase and adenylyl cyclase, will be assayed to assess the relationships between these putative trait markers and the genetic and environmental factors contributing to the aetiology of alcoholism.
The current report is meant to introduce the study design and present a portion of the
preliminary data gathered in the process of establishing this research
program.
Title Low-molecular-weight metabolites relevant to ethanol metabolism: correlation with alcohol withdrawal severity and utility for identification of alcoholics. Author Pronko PS; Velichko MG; Moroz AR; Rubanovich NN Address Institute of Biochemistry, Academy of Sciences of Belarus', Grodno, Belarus'. Source Alcohol Alcohol, 1997 Nov, 32:6, 761-8 Abstract The blood levels of ethanol, acetaldehyde, acetate, methanol, acetone, lactate, pyruvate, and glucose were measured in 23 male alcohol-dependent patients on days 2 to 6 after hospitalization and in 22 healthy male blood donors. Correlations between the biochemical parameters and 17 symptoms of the alcohol-withdrawal syndrome (AWS) were calculated. Abnormally high levels of ethanol, methanol, acetate, and acetone as well as hypoglycaemia were found on day 2, but lactacidaemia and pyruvataemia were pronounced throughout the observation period. AWS severity correlated positively with the acetone content on day 2 and with the acetate content on days 2 to 6.
Negative correlations were found between ethanol levels and craving
for alcohol, methanol levels and craving for alcohol, and between
psychopathologic disorders and the total AWS severity score. The
results suggest that concentrations of blood ethanol, methanol,
acetate, and acetone exceeding their normal endogenous levels can be
used only as indicators of recent heavy drinking. Linear discriminant
analysis using the levels of the nine parameters studied enabled the
correct classification of 91% to 96% of alcoholic patients during 1
week of abstinence and 100% of control subjects. The most informative
parameters in the discrimination between alcoholics and controls were
lactate, pyruvate, the lactate/pyruvate ratio, acetate, and acetone.
Title Decreased inositol 1,4,5-trisphosphate-specific binding in platelets from alcoholic subjects. Author Saito H; Nishida A; Shimizu M; Motohashi N; Yamawaki S Address Department of Psychiatry and Neurosciences, Hiroshima University School of Medicine, Japan. Source Biol Psychiatry, 1996 Nov, 40:9, 886-91 Abstract We measured the degree of inositol 1,4,5-triphosphate (IP3)-specific binding in platelets from alcoholic and nonalcoholic subjects. IP3-specific binding in alcoholic subjects was 45% less than that in nonalcoholic subjects. There was no significant difference in the number of IP3 receptors as detected immunologically in the platelet membrane fractions from alcoholic and nonalcoholic subjects.
These results indicate that the decrease in IP3-specific binding in
alcoholic subjects may have been due to a decreased affinity, but not
number of IP3 binding sites. In contrast to the decrease in IP3
receptor binding, there were no significant changes in phospholipase-C
activity or immunoreactivity of phospholipase C-beta 1 in platelet
membranes from alcoholic subjects. The decreased IP3-specific binding
in platelets may allow for the development of biological markers for
alcoholism.
Title Post mortem markers of chronic alcoholism. Author Sadler DW; Girela E; Pounder DJ Address Department of Forensic Medicine, University of Dundee, Royal Infirmary, UK. Source Forensic Sci Int, 1996 Sep, 82:2, 153-63 Abstract We compared the post mortem diagnostic value of gamma-glutamyltransferase (GGT), carbohydrate-deficient transferrin (CDT), alcoholic liver disease (ALD), blood alcohol concentration (BAC), the presence of multiple bruises and poor hygiene of the feet as markers of chronic alcoholism (heavy continuous drinking) in 32 alcoholics with 32 age-sex matched controls drawn from a forensic autopsy population. Alcoholics and controls were selected on the basis of positive and negative medical history but controls were excluded if BAC exceeded 70 mg%. Femoral venous blood, urine and vitreous humour alcohol concentrations were determined by headspace gas chromatography (GC). BAC was positive in 19 alcoholics (mean 234 mg%, range 2-570 mg%) and six controls (mean 32 mg%, range 2-52 mg%). Serum GGT was measured by a kinetic photometric method, and CDT by both isoelectric focusing/laser densitometry and by a commercial radioimmunoassay kit (CDTect).
Features of alcoholic liver disease were graded
histologically using two weighted scoring systems. Eleven alcoholics
tested positive for GGT, CDTq and ALD, nine were positive for two
tests, five for one test and three were negative for all three tests.
No controls were positive for all three tests but six were positive
for two tests and nine for only one test; 17 were negative for all
three tests. Using the normal clinical cut-off values GGT, CDTq and
CDTect gave poor specificity which was improved at moderate cost to
sensitivity by raising cut off values for each test. Comparison of
receiver operating characteristic curves, likelihood ratios and
post-test odds showed CDT to be the best individual test, followed by
ALD and GGT. Quantitation of CDT by IEF/laser densitometry performed
slightly better than MAEC/RIA by CDTect. CDT shows considerable
promise as a post mortem marker of chronic alcoholism.
Title New 'state' markers for the detection of alcoholism. Author Lesch OM; Walter H Address Universitatsklinik fur Psychiatrie, Vienna, Austria. Source Alcohol Alcohol, 1996 Mar, 31 Suppl 1:, 59-62 Abstract Specific laboratory tests can be used to identify patients who are alcohol-dependent. The laboratory values of a number of biological 'markers', including carbohydrate-deficient transferrin, are often elevated in cases of chronic and acute alcohol abuse. Trait markers reflect a predisposition for alcoholism; state markers reflect actual alcohol consumption. It has been suggested that state markers can be subdivided into screening and relapse markers, and even further subdivided into pre-relapse markers, i.e. craving markers. We hypothesize that methanol metabolism and the presence of condensation products in the blood may serve as state and pre-relapse markers for alcoholism. Since the sensitivities and specificities of laboratory screening tests vary, and an absolute marker for alcoholism has yet to be identified, research in the area of biological markers for alcoholism should continue. Language of Publication English Publication Type Journal Article; Review; Review, Tutorial ISSN 0735-0414 Country of Publication England
Title The "WAM" score: sensitivity and specificity of a user friendly biological screening test for alcohol problems in trauma patients. Author Nilssen O; Ries R; Rivara FP; Gurney JG; Jurkovich GJ Address Department of Psychiatry and Behavioral Sciences, University of Washington, USA. Source Addiction, 1996 Feb, 91:2, 255-62 Abstract Based on a weighted aggregation of three biological alcohol markers (gamma-glutamyltransferase, blood alcohol and mean corpuscular volume), this study presents a screening instrument for alcohol problems in trauma patients. The sex-specific performance of this instrument was explored on 1088 male and 352 female patients, 18 years or older, admitted with blunt or penetrating trauma during a 30-month period to a regional level one trauma center in Seattle, Washington (USA). The sum of the differentially weighted alcohol markers ("WAM"), determined from one blood sample, formed a "score continuum" ranging from 0 to 24. The WAM scores distributed themselves across the trauma population with higher WAM scores being correlated to higher screening instrument scores for alcohol problems. By using two of the best established screening tests for alcohol problems (CAGE and SMAST) to define cut-off points for likely "alcohol abuse/dependence", the WAM score of > or = 7 in males showed 75% sensitivity and 83% specificity, whereas the WAM score of > or = 6 for females displayed 85% sensitivity and 85% specificity.
We conclude that a weighted combination of biological alcohol markers (WAM score) is a useful tool
for identifying alcohol problems among trauma patients. Representing
an alternative or addition to a more extensive interview, it could be
used as a routine part of the care of trauma patients.
Title Enhanced sensitivity of pituitary beta-endorphin to ethanol in subjects at high risk of alcoholism [published erratum appears in Arch Gen Psychiatry 1996 Jun;53(6):555] Author Gianoulakis C; Krishnan B; Thavundayil J Address Department of Psychiatry, McGill University, and Douglas Hospital Research Centre, Verdun, Quebec. Source Arch Gen Psychiatry, 1996 Mar, 53:3, 250-7 Abstract BACKGROUND: Previous studies have demonstrated that a moderate dose of ethanol induced a significant increase in the plasma beta-endorphin content of subjects from families with a history of alcoholism (high risk (HR)), but not subjects from families without a history of alcoholism (low risk (LR)). The objective of this study was to examine the response of the pituitary beta-endorphin and adrenal cortisol systems to various concentrations of ethanol in male and female subjects at high and low risk of the future development of alcoholism. METHODS: All subjects participated in four experimental sessions. In each session the subjects were given a drink containing one of the following doses of ethanol: 0, 0.25, 0.50, and 0.75 g of ethanol per kilogram of body weight (for a 60- to 70-kg individual). Blood samples were taken at 0 minutes and at 15, 45, 120, and 180 minutes after the drink for estimation of the blood alcohol, plasma beta-endorphin, and plasma cortisol levels. RESULTS: The concentration of alcohol in the blood at various intervals after the drink was similar among the subjects, regardless of the risk group. Ethanol increased the plasma level of beta-endorphin-related peptides of the HR but not of the LR subjects in a dose-dependent manner. All subjects showed a small decrease in plasma cortisol level with time, but ethanol ingestion did not significantly alter the plasma cortisol levels.
CONCLUSION: This study indicates that the pituitary beta-endorphin system, but not the
adrenal cortisol system, of the HR subjects shows an enhanced
sensitivity to ethanol, which may be an important factor in
controlling ethanol consumption.
Title Identification of heavy drinkers using a combination of laboratory tests. Author Hartz AJ; Guse C; Kajdacsy Balla A Address College of Medicine, University of Iowa, Dept. of Family Medicine, Iowa City 52242-1097, USA. Source J Clin Epidemiol, 1997 Dec, 50:12, 1357-68 Abstract OBJECTIVE: This study derived and evaluated a model that used results of commonly performed laboratory tests to identify men who are heavy drinkers. METHOD: The results of 40 commonly available laboratory tests were obtained on a diverse sample of 426 heavy drinkers and 188 light drinkers. A logistic regression equation for identifying heavy drinkers was derived in a training data set of 411 subjects and tested in a validation data set of 203 subjects. RESULTS: Ten laboratory measurements were included in the final regression equation: chloride, sodium, ratio of direct to total bilirubin level, blood urea nitrogen, high density lipoproteins, monocyte count, phosphorus, platelets, aspartate aminotransferase, and mean corpuscular hemoglobin. In the validation data this model correctly identified 98% of the 161 heavy drinkers and 95% of the 42 light drinkers. Other models reported in previous literature were applied to these subjects and did not perform as well. The model performed better for subjects of lower socioeconomic status.
CONCLUSIONS: The laboratory tests in our model
may help identify heavy drinkers. The performance of models to
identify heavy drinkers depends on the demographic characteristics of
the subjects.
Title [Carbohydrate-deficient transferrin: a new biochemical marker for chronic excessive alcohol consumption] Author van Pelt J Address St.-Maartens Gasthuis, Klinisch Chemisch en Hematologisch Laboratorium, Venlo. Source Ned Tijdschr Geneeskd, 1997 Apr, 141:16, 773-7 Abstract OBJECTIVE: To assess the usefulness of the biochemical marker 'carbohydrate deficient transferrin' (CDT) in relation to conventional markers for chronic excessive alcohol use. DESIGN: Prospective. SETTING: Addiction clinic Paschalis, Wanssum, the Netherlands. METHOD: Addicts for weaning (n = 125) were questioned at admission about their drinking habits in the last two weeks. Based on the criterion more or less than 60 g alcohol per day, the group was divided into excessive and nonexcessive alcohol users (men: 52 abusers, 51 non-abusers; women: 12 abusers, 10 non-abusers). Mean cell volume (MCV), gamma-glutamyl transpeptidase (gamma GT) and total transferrin were measured in blood collected 2 days after admission, as well as CDT by two methods (CDTect and % CDTriTIA). RESULTS: In men the CDTect test was the most sensitive: sensitivity 82% with specificity 88%. The sensitivity and specificity were 62% and 86% for gamma GT, 50% and 95% for % CDTriTIA, and 34% and 98% for MCV. The combination of a positive CDTect result and a positive gamma GT result gave a predictive value of use of alcohol > 60 g/day of 100%. The results of CDT and gamma GT were also used for a logistic regression model, giving a statistical prediction for excessive alcohol use. The subgroups of women were too small to detect statistical significant differences between tests.
CONCLUSION: The CDTect test was more sensitive for the detection of
chronic excessive alcohol use than the conventional markers. The
combination of gamma GT and CDTect results increased the positive
predictive value.
Title New ways to use biochemical indicators of alcohol abuse to regrant licences in a fairer manner after drunken driving in Germany. Author Iffland R Address Institut fur Rechtsmedizin, Koln, Germany Source Alcohol Alcohol, 1996 Nov, 31:6, 619-20 Abstract The failure of medical-psychological examination to provide convincing recommendations concerning the regranting of licences in a significant number of cases illustrates the need for objective laboratory testing. Experience in Germany shows that blood-alcohol concentration alone could lead to misleading recommendations, and suggests that laboratory testing is best done on samples taken at the time of the offence, rather than subsequently at medical-psychological investigation. Language of Publication English Publication Type Journal Article ISSN 0735-0414 Country of Publication England
Title An 8-year follow-up of 450 sons of alcoholic and control subjects. Author Schuckit MA; Smith TL Address Department of Psychiatry, School of Medicine, University of California-San Diego, San Diego, USA. Source Arch Gen Psychiatry, 1996 Mar, 53:3, 202-10 Abstract BACKGROUND: Between 1978 and 1988, 453 sons (age range, 18-29 years) of alcoholic and control subject were evaluated for their level of reaction (LR) to alcohol. This article presents the results of the 8.2-year follow-up of 450 of these men. The three goals were (1) to attempt to replicate results of the follow-up of the first 223 subjects, (2) to evaluate the potential impact of the quantity and frequency of drinking at the time of the original study on the relationship between LR and alcoholic outcome (ALC), and, most importantly, (3) to test if the relationship between family history (FH) and ALC might be mediated by LR in a subset of the sample. METHODS: Face-to-face structured follow-up interviews were carried out with the subjects and separately with an additional informant, and blood samples, as well as urine specimens, were obtained for determination of state markers of heavy drinking and drug toxicology screens. RESULTS: First, the rate of development of DSM-III-R abuse and dependence on alcohol was 14.1% and 28.6%, respectively, for family history positive (FHP) subjects, compared with 6.6% and 10.8%, respectively, for family history negative (FHN) men. Second, neither consideration of the quantity nor the frequency of drinking at the time of the original study, nor their combination, effectively diminished the relationships between LR and ALC. Third, among men who drank and demonstrated the 15% highest and lowest scores of LR at about the age of 20 years (ie, 30% of the relevant population), the correlation between FH and ALC was greatly reduced when LR was considered, but the correlation between LR and ALC was not greatly diminished when the impact of FH was evaluated.
CONCLUSIONS: In this sample of moderately functional white men, the development of
alcoholism occurred in relationship to an FH of alcoholism, but
alcohol abuse or dependence was unrelated to prior psychiatric
disorders. For this group, LR at the age of 20 years was associated
with future alcoholism in a manner that was independent of the
drinking practices at the time of the original study. At least among
those men with clearly high and low LR scores, these data are
consistent with the conclusion that LR might be a mediator of the
alcoholism risk.
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