γ-Glutamyltranspeptidase and Carbohydrate Deficient Transferrin: Alternative Measures of Excessive Alcohol Consumption

Both γ-glutamyltranspeptidase and carbohydrate-deficient transferrin have been extensively researched as biological markers of heavy alcohol consumption. The current study briefly describes each test, identifies subject variables that influence their relative sensitivities and specificities, and examines issues surrounding use of the two markers in combination. In addition, this study suggests five design features that should characterize projects evaluating the validity of biochemical markers.     

The Effect of Drinking Intensity and Frequency on Serum Carbohydrate-Deficient Transferrin and γ- Glutamyl Transferase Levels in Outpatient Alcoholics

Whereas heavy alcohol consumption is known to elevate serum carbohydrate-deficient transferrin (CDT) and γ-glutamyl transferase (GGT) levels, the contribution of drinking pattern to these effects is not completely understood. We present data on 423 men and 146 women evaluated 1 year after treatment in a large-scale alcoholism treatment study (Project MATCH). Relationships between drinking frequency (number of days drinking), intensity (drinks per drinking day), and blood levels of CDT and GGT were analyzed by using response surface regression models and thin-plate spline-smoothing techniques. Both models indicated differences between CDT- and GGT-drinking pattern relationships in men and, also, a difference between men and women in CDT drinking-pattern relationships. For men, CDT levels appeared to respond primarily to frequency of drinking, whereas GGT was influenced primarily by drinking intensity. For women, both CDT and GGT were influenced more by drinks per drinking day (intensity) than by number of days drinking (frequency). The data confirm both the independent nature of these biological markers of alcohol consumption and gender differences in alcohol-induced CDT response reported previously.     

A Comparison of the Self-Reported Problems of Alcoholics,Drug Dependent Persons,and Multiple Drug Dependent Persons at Admission

Four diagnostic groups of newly admitted patients to Eagleville Hospital's Inpatient Program (A-alcohol dependence only; A + D-primary alcohol dependence, with secondary drug dependence or abuse; D - drug dependence only; D + A-primary drug dependence, with secondary alcohol dependence or abuse) were compared with respect to their self-reported problems on the Substance Abuse Problem Checklist (SAPC). When statistical controls were exercised for sex and age in a threeway ANOVA, the four diagnostic groups evidenced more similarities than differences. Main effect results for diagnosis, independent of age and sex, indicated that multiple substance abusers (MSA's), the A + D and D + A patients, reported significantly more problems on the SAPC than did the single substance abusers (SSA's), the A only and D only patients. This result is believed to be due to the MSA group's greater willingness to report problems early in treatment than the SSA groups.     

Isoelectric Focusing/Western Blotting: A Novel and Practical Method for Quantitation of Carbohydrate-Deficient Transferrin in Alcoholics

Carbohydrate-deficient transferrin (CDT) has been described as the single, most accurate marker of chronic alcohol consumption. Rapid, sensitive, and specific measurement of serum CDT levels can thus provide important clinical information concerning patient diagnosis and treatment. To date, however, methods used for assessing CDT concentrations [e.g., analytical isoelectric focusing combined with immunofixation and micro anion-exchange chromatography followed by radioimmunoassay (RIA)] have not been practical enough for widespread laboratory application. In the present study, we examined the use of a different technique, namely isoelectric focusing (IEF) combined with Western blotting (IEF/WB). Serum proteins (20-40 micrograms) were first focused according to isoelectric points (pI) on high-resolution agarose IEF gels (ampholyte pH range of 5-8) containing nonionic detergent. The focused proteins were transferred electrophoretically to nitrocellulose filters, and then stained immunochemically with antihuman transferrin IgG. IEF/WB completely resolved CDT (focusing at pI 5.7 and 5.9) from other serum transferring isoforms, as assessed with neuraminidase-generated CDT standards. Computerized densitometric scanning of the immunoblots allowed CDT levels to be quantitated directly rather than as a quotient. Serum CDT content determined by IEF/WB was highly correlated (r2 = 0.962; n = 17) with values determined previously by RIA. In a larger subject group, CDT levels (mg/liter) measured by IEF/WB were 139 +/- 54 in recently-drinking alcoholics (n = 58), 81 +/- 8 in abstaining alcoholics (n = 7), and 68 +/- 16 in healthy control subjects (n = 16).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cognitive Performance of Alcoholics: A Longitudinal Evaluation of the Role of Drinking History, Depression, Liver Function, Nutrition, and Family History

To assess the role of drinking history, depression, liver function, nutrition, and family history on cognitive performance, 171 detoxified male alcoholics were administered a brief neuropsychological examination at admission and discharge from an inpatient treatment program and at a 3-month follow-up evaluation. Regression analyses showed that at admission, depression and liver function were significant predictors of neuropsychological performance, whereas at discharge 3 to 4 weeks later only age and an estimate of premorbid intelligence were significant predictors. At the 3-month follow-up, estimates of drinking following discharge and severity of depressive symptoms were major significant predictors of neuropsychological performance. Indices of drinking prior to admission to the treatment program, nutrition, and family history for alcoholism did not predict performance on any of the three test occasions. These findings indicate that in addition to the chronic neurotoxic effect of alcohol a number of different medical and psychiatric factors, as well as the acute effects of alcohol, contribute to the cognitive scores of patients at various points in the clinical course.     

Sensitivity and Specificity of Carbohydrate-Deficient Transferrin as a Marker of Alcohol Abuse Are Significantly Influenced by Alterations in Serum Transferrin: Comparison of Two Methods

Despite a number of investigations suggesting the value of carbohydrate-deficient transferrin (CDT) as a marker of alcohol abuse, a variety of issues on the applicability of CDT measurements in clinical settings have remained unexplored. Earlier studies in this field have focused on the relationship of CDT and the amount of alcohol consumption or presence of liver disease, whereas the influence of alterations in serum transferrin concentrations on CDT has received less attention. In this study, we compared two different methods for measuring CDT (CDTect and %CDT) and total transferrin concentrations in a sample of 83 alcohol abusers (20 patients with alcoholic liver disease and 63 heavy drinkers who were devoid of liver disease, despite excessive alcohol consumption) and 89 controls, who were social drinkers or abstainers. The control population included 53 hospitalized patients with expected abnormalities in serum transferrin concentrations caused by conditions such as negative iron balance, pregnancy, or nonalcoholic liver disease. Both methods gave significantly higher values in alcohol abusers than in controls (p < 0.01), but the overall sensitivity for detecting alcohol abuse was clearly higher for CDTect (59%) than for %CDT (34%). The correlation between the results obtained by the two methods (r= 0.629) significantly improved, when the CDTect values were replaced by the ratio of CDTect/total transferrin (r= 0.770) (p < 0.05). There was a positive correlation between the CDTect and serum transferrin (r= 0.201, p < 0.01), which was significant both in the alcoholics (r= 0.240, p < 0.05), and especially in the controls (r= 0.727, p < 0.001). A significant inverse correlation emerged between %CDT and total transferrin (r= -0.302, p < 0.01). The sensitivities of CDTect and %CDT for correctly classifying alcohol abusers in the subgroup of alcoholic liver disease patients were 90% and 70% and in the subgroup of heavy drinkers without liver disease (49% and 22%), respectively. Specificities for CDTect and %CDT in this sample were 81% and 100%, respectively. However, in the subgroup of hospitalized control patients with abnormal serum transferrin, the specificity of CDTect was only 48%. According to present data, CDTect seems to be more sensitive than %CDT for detecting alcohol abuse. However, any alteration in serum total transferrin concentration markedly decreases the assay specificity. This should be considered when interpreting the assay results in patients with elevated serum transferrin, such as iron deficiency, pregnancy, or liver diseases.     

Detection of Relapses in Alcohol-Dependent Patients: Comparison of Carbohydrate-Deficient Transferrin in Serum, 5-Hydroxytryptophol in Urine, and Self-Reports

In this study, detection of relapses in male alcohol-dependent patients by biochemical markers and self-reports of alcohol consumption were examined. The patients were trying to stay abstinent from alcohol for 6 months. Four of 15 patients dropped out from treatment after 50–110 days. Ratios of urinary 5-hydroxytryptophol (S-HTOL)/5-hydroxyindole-3-acetic acid and 5-HTOL/creatinine were measured daily and serum carbohydrate-deficient transferrin (CDT) once a week. Clinical ratings and self-reports about alcohol consumption were performed three times a week. According to the self-reports, 3 of the patients drank alcohol frequently, 5 of them sporadically, and 7 of the patients reported no alcohol intake at all. According to the 5-HTOL marker, 4 of the patients drank alcohol frequently, and 11 of them sporadically. No one had all urinary levels of 5-HTOL marker below the reference level. According to the CDT, 3 of the patients drank alcohol frequently, 3 sporadically, and in 9 of the patients no elevated levels of CDT were found. Elevated levels of CDT were preceded by increased values of 5-HTOL marker. The combined results suggested that no one of the patients was totally abstinent from alcohol during the treatment period. The 5-HTOL marker seemed to be useful to reveal recent alcohol drinking, and CDT proved to be useful to validate the patients' self-reports. Together the two biochemical markers showed complementary properties in early detection of relapse and treatment monitoring.     

Immunochemical Determination of Serum Transferrin: Reference Values,Correlation with Serum Total Iron-Binding Capacity and Value in the Diagnosis of Iron Deficiency Anaemia and Anaemia of Chronic Disorders

Immunologically determined reference values of serum transferrin are presented for adults and children. A good correlation between serum transferrin and total iron-binding capacity values was found. In 2 groups of anaemic patients - 51 patients with iron deficiency anaemia and 45 patients with anaemia of chronic disorders - serum transferrin determination distinguishes the two groups of anaemic patients from normals somewhat better than TIBC determination.     

A Double-Blind, Placebo-Controlled Study of Nortriptyline and Bromocriptine in Male Alcoholics Subtyped by Comorbid Psychiatric Disorders

This double-blind, placebo-controlled, 6-month follow-up treatment study investigated the efficacy of bromocriptine and nortriptyline in attenuating drinking behavior and psychiatric symptoms in 216 male alcoholic patients subtyped by comorbid psychiatric disorder(s). Three well-defined subtypes were examined: alcoholism only, alcoholism + affective/anxiety disorder, and alcoholism + antisocial personality disorder. It was hypothesized that both medications would relieve negative affective symptoms associated with alcohol use and would be particularly effective for the affective/anxiety subgroup. Contrary to our predictions, the only significant effects found were with the antisocial personality disorder patients who were receiving nortriptyline. One interpretation of the results was that nortriptyline may have reduced impulsive drinking in the antisocial personality disorder subgroup by actions on serotonergic neurotransmission.     

Alcoholics Committed to Treatment: A Prospective Long-Term Study of Behavioral Characteristics, Mortality, and Social Adjustment

Three hundred eighty-three alcoholics, who had at least once been ordered supervision or compulsory treatment at an institution for alcoholics by the Temperance Board, were compared with 383 other alcoholics matched for age and sex. All the alcoholics were first admitted to the Department of Psychiatry, University Hospital, Lund, during the years 1949 to 1969 and followed up until January 1, 1981. They were systematically rated concerning symptoms and etiological factors at first admission. According to a stepwise logistic regression analysis, the following initial symptoms were positively associated with later compulsory treatment: slight cerebral dysfunction/personality change, antisociality/criminality, and impaired social and work performance. Social pressure/responsibility/conflict, slight depression, and continuous drinking were positively associated with the controls. There were 168 deaths in the compulsory treatment group and 124 in the control group (p less than 0.01). The excess deaths in the compulsory treatment group were mainly caused by accidents, poisoning, and violence (21 cases) and sudden cardiac death (10 cases), while there were no differences concerning alcohol-related neoplasms and liver cirrhosis. The compulsory treatment group had a worse long-term social adjustment. The findings indicate that compulsory treatment was related to behavioral patterns showing a stability over time, supporting the validity of subclassification of alcoholics using social data.     

Alcohol-induced Enhancement of Intestinal γ-Glutamyl Transpeptidase Activity in Rats and Humans: A Possible Role in Increased Serum γ-Glutamyl Transpeptidase Activity in Alcoholics

It is a well-known phenomenon that serum gamma-glutamyltranspeptidase (gamma-GTP, EC 2.3.2.2.) activity is increased after chronic consumption of ethanol, and gamma-GTP has been, therefore, widely used as a sensitive marker for detection of alcoholism and its related liver disease. However, the precise mechanisms whereby the chronic ethanol consumption leads to an increase in serum gamma-GTP activity are not fully understood. In the present study, we investigated the relationship between the intestinal and serum gamma-GTP activities after chronic ethanol consumption both in rats and humans. Chronic ethanol feeding to rats resulted in a significant increase in serum gamma-GTP activity associated with a significant increment of the intestinal gamma-GTP activity. The histochemical staining of gamma-GTP in the mucosa of the small intestine of these animals demonstrated enhanced gamma-GTP activity at the microvilli of the brush border membrane, lamina propria of the mucosa, and endoplasmic reticulum of the intestinal epithelial cell. The augmented activity in the lamina propria was mainly localized at the submucosal lymphatics. Histology of the small intestine of human alcoholics was, more or less, similar to those observed in alcoholic rats. We further investigated the gamma-GTP activity in the mesenteric lymph using the animal model of lymphorrhea, and found that the gamma-GTP activity was increased by 83% when expressed per unit of lymph in the ethanol-fed rat, accompanied by a marked decrease of serum gamma-GTP activity, suggesting a close relationship between the serum and the intestinal gamma-GTP via the lymphatic channel.(ABSTRACT TRUNCATED AT 250 WORDS)     

Drinking Patterns and Problems among Female Children and Adolescents: A Comparison of Abstainers,Past Users,and Current Users

The sociopsychological factors that underlie drinking behavior among 197 young girls, ages 9 through 17, are explored. Three groups-youthful abstainers, former users, and current users-were interviewed, as were their parents. These comparison groups are contrasted on 110 variables. The relative merits of four competing explanations of youthful drinking behavior-deprivation, personal deficiency, hedonistic peer culture, and family pathology-are assessed.     

Physical,Chemical, Mechanical,and Biological Properties of Four Different Commercial Root-End Filling Materials: A Comparative Study

Commercial mineral trioxide aggregate (MTA) materials such as Endocem MTA (EC), Dia-Root Bio MTA (DR), RetroMTA (RM), and ProRoot MTA (PR) are increasingly used as root-end filling materials. The aim of this study was to assess and compare the physicochemical and mechanical properties and cytotoxicity of these MTAs. The film thicknesses of EC and DR were considerably less than that of PR; however, RM’s film thickness was greater than that of PR. In addition, the setting times of EC, DR, and RM were shorter than that of PR (p < 0.05). The solubility was not significantly different among all groups. The three relatively new MTA groups (EC, DR, and RM) exhibited a significant difference in pH variation and calcium ion release relative to the PR group (p < 0.05). The radiopacity of the three new MTAs was considerably less than that of PR. The mechanical strength of RM was not significantly different from that of PR (p > 0.05); however, the EC and DR groups were not as strong as PR (p < 0.05). All MTA groups revealed cytocompatibility. In conclusion, the results of this study confirmed that EC, RM, DR, and PR exhibit clinically acceptable physicochemical and mechanical properties and cell cytotoxicity.