Revealing alcohol abuse: to ask or to test?
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Accidents, Traffic↗
Biomedical subjects
A Helander
Publications and source records attributed to A Helander.
Blood-borne factors possibly associated with post-operative nausea and vomiting: an explorative study in women after breast cancer surgery.
BACKGROUND: The pathophysiology behind post-operative nausea and vomiting (PONV) is still not fully understood, especially with respect to gender. According to PONV risk scores, female gender is the strongest predictor for PONV. The risk for PONV after general anaesthesia for breast cancer surgery is 50-80%. The aim of the present explorative study was to identify blood-borne factors that might be associated with the development of PONV in women undergoing breast cancer surgery as a basis for further studies. METHODS: Fifty patients were enrolled prospectively in the study. A standardized sevoflurane-based anaesthetic was used. Blood samples for the analysis of vasopressin, gastrin, cholecystokinin, epinephrine, norepinephrine, dopamine, serotonin, platelet count and blood glucose were taken at six pre-determined time points peri-operatively, and PONV was assessed during 24 h. RESULTS: PONV was found in 27 of 47 patients completing the study. Patients with PONV had a larger variability of the platelet count (P = 0.001), a reduced platelet count on the first post-operative day (P = 0.02) and a less pronounced relationship between the platelet count and whole blood serotonin (P = 0.004) compared with non-PONV patients. A lack of a decrease in epinephrine levels in response to the induction of anaesthesia (P = 0.03) and increased levels of vasopressin (P < 0.001), epinephrine (P = 0.005) and blood glucose (P = 0.004) were observed in the early post-operative period in PONV patients. CONCLUSION: Three different platelet-associated factors and an altered epinephrine pattern were found to be associated with the occurrence of PONV after breast cancer surgery.
Adult↗
Ethyl glucuronide concentrations in two successive urinary voids from drinking drivers: relationship to creatinine content and blood and urine ethanol concentrations.
The concentrations of alcohol in blood (BAC) and two successive urine voids (UAC) from 100 drunk drivers were compared with the concentration of ethyl glucuronide (EtG), a minor metabolite of ethanol in urine, and the urinary creatinine content as an indicator of dilution. The subjects consisted of 87 men with mean age 42.2+/-14.2 years (+/-standard deviation, S.D.) and 13 women with mean age 42.5+/-14.4 years. Ethanol was measured in blood and urine by headspace gas chromatography (GC) and EtG was determined in urine by liquid chromatography-mass spectrometry (LC-MS). The mean UAC was 2.53+/-1.15g/l for first void compared with 2.35+/-1.17g/l for second void, decreasing by 0.18+/-0.24g/l on average (P<0.001 in paired t-test). The ratios of UAC/BAC were 1.35+/-0.25 for first void and 1.20+/-0.16 for second void and the difference of 0.15+/-0.27 was statistically significant (P<0.001). The UAC/BAC ratio was not correlated with creatinine content of the urine specimens, whereas the concentration of urinary EtG was positively correlated with creatinine (r=0.64 for first void and r=0.62 for second void). The UAC was not correlated with urinary EtG directly (r=-0.03 for first void and r=0.08 for second void) but after adjusting for the relative dilution of the specimens (EtG/creatinine ratio) statistically significant positive correlations were obtained (r=0.58 for first void and r=0.57 for second void). The dilution of the urine, as reflected in creatinine content, is important to consider when EtG measurements are interpreted. The excretion of EtG in urine, like glucuronide conjugates of other drugs, is influenced by diuresis. EtG represents a sensitive and specific marker of acute alcohol ingestion with applications in clinical and forensic medicine.
Adult↗
Biological markers in alcoholism.
Alcohol biomarkers include tests indicative of acute or chronic alcohol consumption (state markers), and markers of a genetic predisposition to develop alcohol dependence after chronic exposure (trait markers). While a comprehensive trait marker for alcohol dependence has not been identified, a number of successful state markers for monitoring drinking status are used clinically. These tests provide direct or indirect ways to estimate the amounts of alcohol consumed and the duration of ingestion, and to detect any harmful effects on body functions resulting from long-term misuse. The most obvious method to prove recent drinking is by demonstrating the presence of ethanol in body fluids or breath, but, because ethanol is cleared fairly rapidly from the body, this method is limited to detect only very recent drinking. Measurement of urinary 5-hydroxytryptophol or ethyl glucuronide provide more sensitive methods to disclose recent drinking, because their washout constants are much longer than for ethanol. The liver functions test (GGT, AST and ALT in serum) and the mean corpuscular volume of erythrocytes (MCV) are among the standard diagnostic tools used to identify chronic alcohol exposure. The main disadvantage with these measures is that they have low sensitivity for recent excessive intake, and that raised levels may result from several causes besides heavy drinking, implying a low specificity for alcohol. Carbohydrate-deficient transferrin (CDT), which refers to changes in the carbohydrate composition of serum transferrin, is a more specific marker for identifying excessive alcohol consumption and monitoring abstinence during outpatient treatment. The alcohol biomarkers improves knowledge of drinking patterns in both individuals and populations, and they are also valuable tools for the objective evaluation of treatment efforts. Alcohol markers have, for example, found uses in early identification of at-risk and harmful drinking, and they help to monitor abstinence and relapse in response to outpatient treatment.
Alcoholism↗
An outbreak of gastroenteritis in Osaka, Japan due to Escherichia coli serogroup O166:H15 that had a coding gene for enteroaggregative E. coli heat-stable enterotoxin 1 (EAST1).
In an outbreak of gastroenteritis on 23 July 1996, in Osaka, Japan, 54 of 91 persons who had attended a meeting the previous day became ill. Escherichia coli O166:H15 was isolated from stool specimens of patients (29/33, 88%). Laboratory tests for other bacterial pathogens and viruses were negative. The E. coli 0166 organisms did not adhere to HEp-2 cells in a localized, diffuse, or enteroaggregative manner. The organisms did not express known enterotoxigenic E. coli (ETEC) colonization factors. In polymerase chain reaction tests, the bacteria did not have coding genes for shigatoxin of enterohemorrhagic E. coli (EHEC), heat-labile, or heat-stable enterotoxin of ETEC, attachment and effacement (eaeA) of EPEC, or invasion (invE) of enteroinvasive E. coli (EIEC). Consequently, they could not be assigned to any of the recognized diarrhoeagenic groups of E. coli: EPEC, ETEC, EHEC, EIEC, enteroaggregative E. coli (EAggEC), or diffusely adhering E. coli. However, the organisms possessed the EAggEC heat-stable enterotoxin (EAST1) gene. To our knowledge, this is the first report of an outbreak caused by E. coli that did not have well-characterized virulence genes other than EAST1. The isolates showed the same DNA banding pattern in pulsed-field gel electrophoresis after digestion with the restriction enzymes XbaI or NotI. Three O166:H15 strains isolated from two sporadic cases and another outbreak during 1997-8 were distinct, indicating that multiple clones have spread already. We propose that diarrhoeal specimens should be examined for E. coli possessing the EAST1 gene.
Base Sequence↗
The effect of total body water on the relationship between alcohol consumption and carbohydrate-deficient transferrin.
BACKGROUND: Clinicians agree that alcoholism commonly is overlooked in their patients, and that treating the symptoms without directing therapy to the underlying cause at best delays an inevitable decline in the patient's general health and well-being. The current analysis focused on carbohydrate-deficient transferrin (CDT), a promising biological marker of dangerous alcohol consumption. METHODS: Included in our study were men (730) and women (613) from study sites in Canada, Brazil, and Japan. All subjects were participants in the WHO/ISBRA Study on State and Trait Markers of Alcoholism, who completed an extensive demographic, medical, and behavioral survey and provided blood samples for determination of CDT levels. ANOVA and chi2 test for equality were used to examine the effect of total body water (TBW) on the alcohol consumption/CDT relationship. To examine whether accounting for differences in TBW improved the diagnostic properties of CDT when used as a state marker for alcohol consumption, odds ratios were calculated for men and women separately. RESULTS: Our results show that accounting for individual differences in TBW significantly influenced the alcohol consumption/CDT dose-response relationship. The effect of TBW was different for men compared with women. When we used a consumption cutoff value of 40 g/day and the CDTect recommended cutoffs (20 for men; 27 for women), adjusting for differences in TBW significantly increased diagnostic performance of CDT in men but not women. CONCLUSIONS: The dependence of CDT measures on body water content needs to be taken into account to maximize the performance of CDT as an effective state marker of alcohol consumption in males.
Adolescent↗
[Is it possible to boil away alcohol from the glogg-wine?].
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Cooking↗
[CDT a valuable marker of overconsumption of alcohol. Guidelines for its use in connection with automobile driver examination].
According to the medical regulations for obtaining a driver's license in Sweden, alcohol abuse/dependency constitutes sufficient grounds for denial. In the case of a conviction for gross drunk driving, it is incumbent upon the offender to present a medical certificate verifying a "sober lifestyle". Biological markers are important tools for proving alcohol abuse in each of these contexts. In this connection, CDT analyses play a key role through their high marked specificity for increased alcohol consumption. The authors have agreed upon the guidelines as presented in this paper for determining sobriety as it pertains to possession of a driver's license. Special emphasis is placed on how CDT tests should be used and interpreted in such contexts, as well as their value as evidence in the case of increased CDT levels.
Alcohol Drinking↗
Comparison of self-reported alcohol intake with the urinary excretion of 5-hydroxytryptophol:5-hydroxyindole-3-acetic acid, a biomarker of recent alcohol intake.
Under-reporting of alcohol intake has been frequently reported. However, due to the lack of an objective reference method, e.g. a biomarker, information about the extent of under-reporting of alcohol intake obtained with dietary assessment instruments is not available. The objective of this study was to compare reported alcohol intake data derived from a 24 h recall with a biomarker of recent alcohol intake, the urinary excretion of 5-hydroxytryptophol (5-HTOL):5-hydroxyindole-3-acetic acid (5-HIAA). Embedded into the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study, Germany, a validation study that collected 24 h recall data and 24 h urine samples was conducted. Cohort study participants (n 107) volunteered to participate in this validation study. Among them were five subjects who reported no consumption of alcoholic beverages but had a 5-HTOL:5-HIAA ratio that indicated recent alcohol intake when the clinical cut-off point was taken as a judging criterion. After exclusion of these under-reporters, the Pearson's correlation coefficient between reported alcohol intake and the 5-HTOL:5-HIAA ratio was 0.92 (P<0.0001). Except for low alcohol intake of <0.1 g/kg body mass, a significant increase in 5-HTOL:5-HIAA excretion was observed with increasing amounts of alcohol intake. In conclusion, the 5-HTOL:5-HIAA excretion ratio appears to be a valuable quantitative biomarker of recent alcohol consumption. Denial of alcohol intake can be detected, but for the quantification of under-reporting of alcohol intake 24 h reference data are not yet available. With these data at hand, however, 5-HTOL:5-HIAA could become a biomarker for validation purposes in nutritional epidemiology.
5-Hydroxytryptophan↗
WHP/ISBRA study on state and trait markers in alcoholism.
This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chair was Boris Tabakoff. The presentations were (1) Overview of the WHO/ISBRA study on state and trait markers in alcoholism, by Boris Tabakoff; (2) Biochemical markers of acute and chronic drinking: Results of the WHO/ISBRA study, by Anders Helander; (3) The impact of country of recruitment and body mass index on biological marker dose-response curves in the WHO/ISBRA Study, by Kate M. Conigrave; (4) Relationship of body water to carbohydrate-deficient transferrin measures, by Larry Martinez; and (5) Platelet adenylyl cyclase activity as a trait marker of alcohol dependence, by Paula L. Hoffman.
Adenylyl Cyclases↗
Perioperative morbidity and mortality in chronic alcoholic patients.
This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Claudia Spies and Hanne Tønnesen. The presentations were (1) Relevance of alcohol misuse in surgical patients, by Hanne Tønnesen; (2) Diagnosis of alcohol abuse and alcohol dependence, by Sven Andreasson; (3) Diagnosis of acute alcohol misuse, by Anders Helander; (4) Preoperative intervention for excessive alcohol consumption, by Kate Conigrave; and (5) Prevention and treatment of perioperative complications in chronic alcoholics, by Claudia Spies.
Alcoholism↗
Interference of transferrin isoform types with carbohydrate-deficient transferrin quantification in the identification of alcohol abuse.
BACKGROUND: Isoforms of transferrin interfere with measurement of carbohydrate-deficient transferrin (CDT) as a marker of heavy alcohol consumption. We evaluated the rate of inaccurate CDT results by immunoassays. METHODS: We studied 2360 consecutive sera (1614 individuals) submitted for CDT assay without clinical information as well as samples from 1 patient with a congenital disorder of glycosylation (CDG Ia) and from 6 healthy carriers of CDG Ia. The CDTect, %CDT-TIA, and new %CDT immunoassays were compared with HPLC (%CDT-HPLC). Transferrin isoform pattern were evaluated by isoelectric focusing (IEF). RESULTS: Transferrin BC and CD heterozygotes were found at frequencies of approximately 0.7% and approximately 0.2%, respectively. Another transferrin C subtype, where di- and trisialotransferrin partly coeluted (tentatively identified as C2C3), was observed in approximately 0.6%. Compared with the %CDT-HPLC method, the immunoassays often produced low results for transferrin BC and high results for transferrin CD and "C2C3". A very high trisialotransferrin value (frequency approximately 1%) often produced high CDT immunoassay results. In four of six healthy carriers of CDG Ia, a- and disialotransferrin were highly increased and the HPLC and IEF isoform patterns were indistinguishable from those in alcohol abuse. CONCLUSIONS: Rare transferrin isoform types and abnormal amounts of trisialotransferrin (total frequency approximately 2-3%) may cause incorrect determination of CDT with immunoassays. The observed variants were readily identified by HPLC and IEF, which can be recommended for verification of CDT immunoassay results in doubtful cases. In healthy carriers of CDG Ia, CDT is high by all assays.
Alcoholism↗
Dietary serotonin and alcohol combined may provoke adverse physiological symptoms due to 5-hydroxytryptophol.
The urinary excretion products of serotonin (5-hydroxytryptamine, 5HT) are 5-hydroxyindole-3-acetic acid (5HIAA) and 5-hydroxytryptophol (5HTOL), and the ratio of 5HTOL to 5HIAA is normally very low (< 0.01 ) in man. Intake of foods rich in 5HT (high amounts in banana, pineapple, and walnuts) induces a general increase in the output of 5HT metabolites, without affecting the 5HTOL/5HIAA ratio. In contrast, during metabolism of ethanol there is a shift in the catabolic pattern of 5HT, and the formation of 5HTOL increases appreciably at the expense of 5HIAA. Accordingly, the urinary 5HTOL/ 5HIAA ratio increases and does not recover to baseline levels until several hours after ethanol has been cleared from the body. When 10 healthy subjects ingested a moderate dose of ethanol (0.5 g/kg), the urinary 5HTOL/SHIAA ratio was increased approximately 70-fold on average at 4 h after intake. When the same amount of ethanol was ingested together with 3 bananas (approximately 10 mg 5HT), this ratio was increased approximately 100-fold at 4 h and still significantly higher than baseline levels at 24 h. Starting at 3-4 h after the combined intake of ethanol and banana, 7 subjects experienced one or more unpleasant symptoms (diarrhea, headache, and fatigue) which are associated with the 5HT system. The events were transient but typically lasted for several hours, and the duration correlated with the time period during which 5HTOL levels were raised. Intake of ethanol and banana separately produced much lower increases in 5HTOL output and caused no corresponding effects. This observation indicate that dietary 5HT intake together with even a moderate dose of ethanol can provoke unpleasant physiological symptoms. The symptoms may be attributed to the high concentration of 5HTOL.
Adult↗
Human antibody response to longus type IV pilus and study of its prevalence among enterotoxigenic Escherichia coli in Bangladesh by using monoclonal antibodies.
Mouse monoclonal antibodies (MAbs) were derived against longus (CS20), a type IV pilus expressed by human enterotoxigenic Escherichia coli (ETEC). One MAb (ICA39) detected longus in 56 (8.5%) of 662 ETEC isolates obtained from a routine surveillance of diarrheal stools from children and adults. Five patients with diarrhea from whom longus-positive ETEC were isolated were also recruited. Of these 61 isolates, 50 were positive for other colonization factors (CFs; 61% for CFA/II and 21% for CFA/I), and 11 were negative for any of the other 8 CFs that were tested. They were either positive for the heat-stable enterotoxin (ST; n=29) or for the heat-labile enterotoxin (LT) and ST (n=32). All longus-positive ETEC were confirmed by polymerase chain reaction to harbor lngA, the longus structural pilin gene. Sera and/or fecal extracts from the patients reacted with the 22-kDa pilin polypeptide in immunoblots and ELISA. These studies show that longus is prevalent among ETEC in Bangladesh and that longus gives rise to IgA antibody responses in patients.
Adult↗
Studies on the interaction between ethanol and serotonin metabolism in rat, using deuterated ethanol and 4-methylpyrazole.
The metabolic interaction between ethanol and serotonin (5-hydroxytryptamine) via alcohol dehydrogenase (ADH; EC 1.1.1.1) was studied in tissue homogenates of Sprague-Dawley rats by following the transfer of deuterium from deuterated ethanol over endogenous NADH to 5-hydroxytryptophol (5HTOL). Homogenates of whole brain, lung, spleen, kidney, liver, stomach, jejunum, ileum, colon, and caecum were incubated in the presence of [2H2]ethanol and 5-hydroxyindole-3-acetaldehyde (5HIAL), and the [2H]5HTOL formed was identified and quantified using gas chromatography-mass spectrometry. ADH activity was most abundant in liver, kidney, and within the gastrointestinal tract. The highest incorporation of deuterium was obtained in homogenates of kidney, lung, and colon, whereas in brain, which contains very low ADH activity, no incorporation could be demonstrated. Addition of extra NAD+ (2.4 mM) increased the formation of [2H]5HTOL 2.6-fold in liver homogenates, but only 1.2-fold in kidney homogenates. 4-Methylpyrazole, a potent inhibitor of class I ADH, inhibited the 5HIAL reduction in homogenates of lung, kidney, jejunum, ileum, and colon, and caused a marked drop in 5HTOL oxidation in all tissues except stomach and spleen. These results demonstrate that in the rat a metabolic interaction between ethanol and serotonin via the ADH pathway may take place in several tissues besides the liver, which is the main tissue for ethanol detoxification.
Alcohol Dehydrogenase↗
Misleading results of ethanol analysis in urine specimens from rape victims suffering from diabetes.
We report appreciably high concentrations of ethanol (82 and 102 mg/dL) in specimens of urine collected from two victims of date rape. Both girls (aged 15 and 18 years) suffered from diabetes mellitus, but adamantly denied drinking any alcohol before or after the incident. The presence of glycosuria and high risk of fungal infections in female diabetics suggests that ethanol was produced in vitro by fermentation after voiding. Making a routine test for sugar in the urine and ensuring that the sampling tubes contain sufficient sodium or potassium fluoride to inhibit glycolysis are recommended practices. A specific marker for post-sampling synthesis of ethanol might also be used such as the 5HTOL/5HIAA ratio.
Journal Article↗
The Alcohol Use Disorders Identification Test (AUDIT) and carbohydrate-deficient transferrin (CDT) in a routine workplace health examination.
BACKGROUND: Only a few studies on workplaces have examined the Alcohol Use Disorders Identification Test (AUDIT) or carbohydrate-deficient transferrin (CDT) as screening instruments for the early identification of elevated and risky levels of alcohol consumption. The purpose of this study was to compare the performances of AUDIT, CDT, and gamma-glutamyltransferase (GGT) in a routine health examination (alcohol screening) in the workplace. METHODS: The study, carried out over 16 months in a large workplace in the transport sector, was part of an on-going controlled study. Employees who came to the company health service for a routine health examination were offered the opportunity to undergo an alcohol screening and check their alcohol habits. RESULTS: Of the 570 subjects who participated, 105 (18.4%) screened positive according to AUDIT, CDT, or both. Only 7.6% of the persons who screened positive did so according to both instruments. If GGT had been included as a screening instrument, the proportion of positive results would have increased to 22.0%. If we had only used AUDIT in the screening process, the proportion of positives would have fallen by nearly half. CONCLUSIONS: The present findings suggest that AUDIT and CDT are complementary instruments for alcohol screening in a routine workplace health examination, and each has value for identifying a different segment of the risky drinking population.
Adult↗
Platelet adenylyl cyclase activity as a trait marker of alcohol dependence. WHO/ISBRA Collaborative Study Investigators. International Society for Biomedical Research on Alcoholism.
BACKGROUND: There is compelling evidence that genetic factors play a major role in the development of alcohol dependence. Platelet adenylyl cyclase (AC) activity has been proposed as a biochemical marker for differentiating alcohol-dependent and nondependent subjects, but the sensitivity and specificity of this marker have not been ascertained. The objective of this study was to determine the sensitivity and specificity of platelet AC activity in identifying alcohol-dependent subjects and to ascertain the effect of medical/ psychiatric variables, drinking and smoking history, and age and body weight on AC activity. METHODS: The cross-sectional study was conducted from 1995 to 1998. Participants were 210 Australian White men who were community volunteers and alcohol treatment inpatients in Sydney, Australia. There were 41 nondrinkers, 140 drinkers, and 29 men who were entering alcohol treatment. The main outcome measure was platelet AC activity. Classification variables were plasma ethanol, gamma-glutamyltransferase, aspartate aminotransferase, serum carbohydrate-deficient transferrin (CDT), and urinary 5-hydroxytryptophol/5-hydroxyindoleacetic acid (5-HTOL/5-HIAA) levels, and World Health Organization/International Society for Biomedical Research on Alcoholism Interview Schedule variables, which included alcohol use and dependence criteria. RESULTS: Among subjects who reported abstinence for at least 4 days, both cesium fluoride (CsF)- and forskolin-stimulated platelet AC activities were significantly lower in those with a lifetime history of alcohol dependence compared with those with no such history (p < 0.005 and p < 0.05, respectively). The sensitivity and specificity of CsF-stimulated AC activity to discriminate individuals with a lifetime history of alcohol dependence were 75% and 79%, respectively. Similar values for sensitivity and specificity for CsF-stimulated AC activity were calculated when discriminating current alcohol dependence in the subjects in our sample. Irrespective of the history of alcohol dependence, persons who had consumed alcohol recently (within the last 3-4 days) showed significantly higher mean basal, CsF-stimulated, and forskolin-stimulated AC activity (p < 0.001), as did those who had elevated 5-HTOL/5-HIAA ratios or CDT levels, indicative of recent (heavy) drinking. The "normalization" of platelet AC activity to baseline levels after an individual stops drinking may be related to the generation of new platelets during the abstinence period. Conduct disorder and antisocial personality disorder were not associated with low AC activity, but low forskolin-stimulated AC activity was associated with major depression. CONCLUSIONS: We found that CsF- and forskolin-stimulated platelet AC activity discriminates between subjects with and without alcohol dependence in a population of subjects who had not consumed significant quantities of ethanol recently. Recent alcohol consumption is a confounding variable that can alter the measured levels of AC activity. Forskolin-stimulated platelet AC activity also may be influenced by a history of major depression.
Adenylyl Cyclases↗