Search

Background: The Alcohol Use Disorders Identification Test (AUDIT) has been extensively researched to determine its capability to accurately and practically screen for alcohol problems. Methods: During the 5 years since our previous review of the literature, a large number of additional studies have been published on the AUDIT, abbreviated versions of it, its psychometric properties, and the applicability of the AUDIT for a diverse array of populations. The current article summarizes new findings and integrates them with results of previous research. It also suggests some issues that we believe are particularly in need of further study. Results: A growing body of research evidence supports the criterion validity of English version of the AUDIT as a screen for alcohol dependence as well as for less severe alcohol problems. Nevertheless, the cut-points for effective detection of hazardous drinking as well as identification of alcohol dependence or harmful use in women need to be lowered from the originally recommended value of 8 points. The AUDIT-C, the most popular short version of the AUDIT consisting solely of its 3 consumption items, is approximately equal in accuracy to the full AUDIT. Psychometric properties of the AUDIT, such as test–retest reliability and internal consistency, are quite favorable. Continued research is urged to establish the psychometric properties of non-English versions of the AUDIT, use of the AUDIT with adolescents and with older adults, and selective inclusion of alcohol biomarkers with the AUDIT in some instances. Conclusions: Research continues to support use of the AUDIT as a means of screening for the spectrum of alcohol use disorders in various settings and with diverse populations.

Successfully managing group dynamics of small, physically isolated groups is vital for long duration space exploration/habitation and for terrestrial CELSS (Controlled Environmental Life Support System) facilities with human participants. Biosphere 2 had important differences and shares some key commonalities with both Antarctic and space environments. There were a multitude of stress factors during the first two year closure experiment as well as mitigating factors. A helpful tool used at Biosphere 2 was the work of W.R. Bion who identified two competing modalities of behavior in small groups. Task-oriented groups are governed by conscious acceptance of goals, reality-thinking in relation to time and resources, and intelligent management of challenges. The opposing unconscious mode, the "basic-assumption" ("group animal") group, manifests through Dependency/Kill the Leader, Fight/Flight and Pairing. These unconscious dynamics undermine and can defeat the task group's goal. The biospherians experienced some dynamics seen in other isolated teams: factions developing reflecting personal chemistry and disagreements on overall mission procedures. These conflicts were exacerbated by external power struggles which enlisted support of those inside. Nevertheless, the crew evolved a coherent, creative life style to deal with some of the deprivations of isolation. The experience of the first two year closure of Biosphere 2 vividly illustrates both vicissitudes and management of group dynamics. The crew overrode inevitable frictions to creatively manage both operational and research demands and opportunities of the facility, thus staying 'on task' in Bion's group dynamics terminology. The understanding that Biosphere 2 was their life support system may also have helped the mission to succeed. Insights from the Biosphere 2 experience can help space and remote missions cope successfully with the inherent challenges of small, isolated crews.

Background Ethyl sulphate (EtS), a direct ethanol metabolite, appears to offer potential as a biomarker for recent alcohol consumption. Although its window of assessment is similar to that of ethyl glucuronide (EtG), there are differences between the two markers in their pathways for formation and degradation. Aims (a) To assess the excretion of EtS compared to EtG and ethanol in drinking experiments with healthy volunteers, and (b) to elucidate the possibility of using the two metabolites for monitoring abstinence in substance use disorder patients during rehabilitation treatment. Design, setting, participants (a) Nine drinking experiments were performed by six healthy volunteers (two females, four males), with a mean age of 34.1 years (20–62), average oral intake of 0.2 g/kg ethanol (0.1–0.61), and having 74 spot urine samples. (b) Thirty-six substance abuse patients (mean age 41.9 years, 20–59; 22 males, 14 females) in a rehabilitation programme after withdrawal, producing 98 urine samples. Ethyl glucuronide and ethyl sulphate were measured using liquid chromatography tandem mass spectrometry (LC-MS/MS) using d5-EtG and d5-EtS, respectively, as an internal standard. Findings (a) Volunteers: EtG and EtS were detectable for up to 36 hours and reached the limits of determination in urine at 20.6 hours and 21.2 hours (median), respectively, after ethanol intake. EtG-100 (standardized to a creatinine of 100 mg/dl) reached its maximum level at 2.8 hours and EtS-100 at 2.1 hours (median) after the beginning of the experiment. Of the ethanol ingested, 0.022% was excreted as EtS in one volunteer. Eight samples were positive for EtS only and six for EtG only. Spearman's rank correlation coefficients of 0.84 (P

As, for ethical reasons, it is difficult to investigate by an experiment the effect of acute intoxication on leptin levels in alcoholics, we tested the hypothesis of lowered levels as an effect of acute ethanol intake inhealthy volunteers. The subjects comprised (1) 17 healthy male participants, recruited via newspaper advertisements [age 29 + 3.75 years, body mass index (BMI) 24.3 + 3.5, leptin at baseline 3.3 + 3.1 ng/ml]; (2) for comparison, leptin levels of 16 male alcoholic patients at day I of withdrawal were used. They were characterized as follows: (mean, median, standard deviation and range) age in years (41.1, 40.5, 10.2, 24, 57), BMI (23.3, 21.7, 5.4, 16.6, 37.5), 1032g of ethanol (median) consumed within the last 7 days, leptin levels 2.3mglml. A placebo-controlled double-blind trial teas performed. Leptin levels of blood samples were taken at baseline (t 1 ), before ethanol intake (t 2 ), when blood alcohol had reached its maximum (t 3 ) and the morning after (t 4 ). The oral dose of ethanol administered was 0.6 g/kg ethanol. (1) Volunteers: (a) the ethanol and placebo group exhibited leptin levels corresponding closely with levels measured at baseline (t 1 ) (rs = 0.85, p < 0.0001) and follow-up (t 4 ) (r s = 0.768, p < 0.0001). (b) Leptin levels for the placebo and the alcohol-consuming (verum) group did not differ significantly at baseline, after ethanol intake or on the morning after [Mann - Whitney U-test (p = 0.669, p = 1.0 and p = 0.887, respectively)]. (2) Leptin levels in relation to BMI did not significantly differ at any measurement time in either group. (3) Leptin levels/BMI of the healthy volunteers at t 1 and t 4 were not significantly different from those of 16 alcoholics. The data do not support the hypothesis of a significant effect of acute moderate alcohol intake on leptin levels in healthy volunteers.

Background: Biochemical markers of heavy drinking are playing increasingly prominent roles in alcohol treatment efficacy studies, especially in those designed to evaluate medications. Among these roles are serving as inclusion or exclusion criteria for research participants, corroboration of self-report of drinking status, assessment of the safety of the agent being evaluated, and determination of treatment outcome. Methods: Recent alcohol medication development trials that included biomarker information were reviewed and critiqued from the perspectives of how biomarker measures were used and how findings on them were reported. Results: Although generally the application of biomarkers as inclusion criteria is not recommended, they may aid in exclusion of potential subjects (e.g., elevated liver function measures in trials of agents that could result in liver damage). Biomarkers are most commonly used as indicators of outcome, usually serving as secondary outcome variables. The relationship of outcome findings on biomarker and self-report measures is positive, but only moderate. As used to date, biomarkers of drinking tend to be less sensitive than well-standardized and properly administered self-report measures. Nevertheless, they do provide a useful, unique source of information on drinking status. Conclusions: The contribution of biomarkers to alcoholism clinical research would be enhanced if certain design strategies were incorporated into their application and if critical information were included in the research publication. This article offers a series of recommendations to improve on their use in a research context.

The unprecedented challenges of creating Biosphere 2, the world's first laboratory for biospherics, the study of global ecology and long-term closed ecological system dynamics, led to breakthrough developments in many fields, and a deeper understanding of the opportunities and difficulties of material closure. This paper will review accomplishments and challenges, citing some of the key research findings and publications that have resulted from the experiments in Biosphere 2. Engineering accomplishments included development of a technique for variable volume to deal with pressure differences between the facility and outside environment, developing methods of atmospheric leak detection and sealing, while achieving new standards of closure, with an annual atmospheric leakrate of less than 10%, or less than 300 ppm per day. This degree of closure permitted detailed tracking of carbon dioxide, oxygen, and trice gases such as nitrous oxide and ethylene over the seasonal variability of two years. Full closure also necessitated developing new approaches and technologies for complete air, water, and wastewater recycle and reuse within the facility. The development of a soil-based highly productive agricultural system was a first in closed ecological systems, and much was learned about managing a wide variety of crops using non-chemical means of pest and disease control. Closed ecological systems have different temporal biogeochemical cycling and ranges of atmospheric components because of their smaller reservoirs of air, water and soil, and higher concentration of biomass, and Biosphere 2 provided detailed examination and modeling of these accelerated cycles over a period of closure which measured in years. Medical research inside Biosphere 2 included the effects on humans of lowered oxygen: the discovery that human productivity can be maintained with good health with lowered atmospheric oxygen levels could lead to major economies on the design of space stations and planetary/lunar settlements. The improved health resulting from the calorie-restricted but nutrient dense Biosphere 2 diet was the first such scientifically controlled experiment with humans. The success of Biosphere 2 in creating a diversity of terrestrial and marine environments, from rainforest to coral reef, allowed detailed studies with comprehensive measurements such that the dynamics of these complex biomic systems are now better understood. The coral reef ecosystem, the largest artificial reef ever built, catalyzed methods of study now being applied to planetary coral reef systems. Restoration ecology advanced through the creation and study of the dynamics of adaptation and self-organization of the biomes in Biosphere 2. The international interest that Biosphere 2 generated has given new impetus to the public recognition of the sciences of biospheres (biospherics), biomes and closed ecological life systems. The facility, although no longer a materially-closed ecological system, is being used as an educational facility by Columbia University as an introduction to the study of the biosphere and complex system ecology and for carbon dioxide impacts utilizing the complex ecosystems created in Biosphere '.The many lessons learned from Biosphere 2 are being used by its key team of creators in their design and operation of a laboratory-sized closed ecological system, the Laboratory Biosphere, in operation as of March 2002, and for the design of a Mars on Earth ™ prototype life support system for manned missions to Mars and Mars surface habitats. Biosphere 2 is an important foundation for future advances in biospherics and closed ecological system research.

Research and design of subsurface flow wetland wastewater treatment systems for a ground-based experimental prototype Mars Base facility has been carried out, using a subsurface flow approach. These systems have distinct advantages in planetary exploration scenarios: they are odorless, relatively low-labor and low-energy, assist in purification of water and recycling of atmospheric CO2, and will support some food crops. An area of 6-8 m2 may be sufficient for integration of wetland wastewater treatment with a prototype Mars Base supporting 4-5 people. Discharge water from the wetland system will be used as irrigation water for the agricultural crop area, thus ensuring complete recycling and utilization of nutrients. Since the primary requirements for wetland treatment systems are warm temperatures and lighting, such bioregenerative systems may be integrated into early Mars base habitats, since waste heat from the lights may be used for temperature maintenance in the human living environment. "Wastewater gardens (TM)" can be modified for space habitats to lower space and mass requirements. Many of its construction requirements can eventually be met with use of in-situ materials, such as gravel from the Mars surface. Because the technology requires little machinery and no chemicals, and relies more on natural ecological mechanisms (microbial and plant metabolism), maintenance requirements are minimized, and systems can be expected to have long operating lifetimes. Research needs include suitability of Martian soil and gravel for wetland systems, system sealing and liner options in a Mars Base, and wetland water quality efficiency under varying temperature and light regimes.

The parallels between the challenges facing bioregenerative life support in artificial closed ecological systems and those in our global biosphere are striking. At the scale of the current global technosphere and expanding human population, it is increasingly obvious that the biosphere can no longer safely buffer and absorb technogenic and anthropogenic pollutants. The loss of biodiversity, reliance on non-renewable natural resources, and conversion of once wild ecosystems for human use with attendant desertification/soil erosion, has led to a shift of consciousness and the widespread call for sustainability of human activities. For researchers working on bioregenerative life support in closed systems, the small volumes and faster cycling times than in the Earth's biosphere make it starkly clear that systems must be designed to ensure renewal of water and atmosphere, nutrient recycling, production of healthy food, and safe environmental methods of maintaining technical systems. The development of technical systems that can be fully integrated and supportive of living systems is a harbinger of new perspectives as well as technologies in the global environment. In addition, closed system bioregenerative life support offers opportunities for public education and consciousness changing of how to live with our global biosphere.

Although the primary use of biochemical markers of heavy drinking is to assist in screening for alcohol problems, laboratory tests may also aid in early identification of relapse. This report reviews research findings on a new marker, carbohydrate deficient transferrin (CDT), in alcoholics receiving treatment or in follow-up. It also offers recommendations on how CDT may be employed by clinicians monitoring drinking status.

Alcoholism treatment research has traditionally focused on direct questions of efficacy, such as is a particular intervention better than no treatment or is one treatment more effective than another. Recent projects, however, have also attempted to identify variables explaining why treatments vary in their effects. Many of these variables relate to the process of treatment itself or changes that may occur within the patients. Clinicians also need to continuously monitor progress of patients in engaging in behaviors supportive of long-term sobriety and how well the values and behaviors fostered by the particular treatment regimen are being incorporated into daily life. Measurement of process variables may assist in both regards. In the last decade several psychometric instruments have been developed to elucidate the processes involved in Alcoholic Anonymous (AA), a key adjunct of most formal alcoholism programs in the United States. These instruments measure dimensions such as involvement in AA, completion of steps, and adoption of values encouraged by AA. Six such measures are summarized here and several fruitful topics for future research on the measures are suggested.

Objective Surveys assessing alcohol use among physicians have most commonly employed the Alcohol Use Disorders Identification Test (AUDIT) or the AUDIT-C, the most common short version of the AUDIT. As with other screeners, prevalence estimation is dependent on the accuracy of the test as well as choice of the cutoff value. The aim of the current study is to derive more precise prevalence estimates of alcohol problems in physicians by correcting for false-positive and false-negative results. Method In the context of a survey, the AUDIT was sent out via email or standard postal service to all 2484 physicians in Salzburg, Austria. A total of 456 physicians participated. A published correction formula was used to estimate the real prevalence of alcohol use problems. Results Applying a cutoff of 5 points for the AUDIT-C, 15.7% of female and 37.7% of male physicians screened positive. Use of a correction based on general population data and the sensitivity and specificity of the AUDIT-C resulted in much lower prevalence rates: 4.0% for female and 9.5% for male physicians. Using the full AUDIT, 19.6% of the female physicians and 48% of the male physicians were screened positive. Using the correction, the estimated prevalence rates for females and males were 6.3% and 15.5%, respectively. Conclusions Our findings demonstrate that uncorrected screening results may markedly overestimate the prevalence of physicians drinking problems.

Current trends in conceptions of alcohol problems and provision of health care put increased emphasis on identifying individuals whose alcohol use and problems cover a range of severity. The purpose of this study is to begin to provide information on the relative utility of self-report measures designed to identify (screen for) individuals with alcohol problems. To achieve this goal, the empirical literature on contrasts of self-report screening measures was reviewed, and 13 relevant studies across diverse settings and subject populations were identified. The review showed that the CAGE, the Michigan Alcoholism Screening Test (MAST), and the short MAST (sMAST) have been the most widely studied self-report instruments to screen for alcohol problems. Direct comparisons show the MAST to be more sensitive than the CAGE, but with elderly patients the CAGE may perform better than the MAST. Furthermore, available data suggest that the CAGE and the sMAST perform comparably. Finally, the CAGE, MAST, and sMAST all perform best when predicting criteria most similar to those the instruments were designed to reflect. The study concludes with a discussion of priorities for research on screening instruments.

The accurate assessment of drinking by patients with alcoholic liver disease is important both before and after liver transplantation. Unfortunately, self-reports by these individuals often underestimate their actual alcohol consumption. Several recently developed biochemical measures can provide additional information on a patient's use of alcohol. This article describes ethyl glucuronide, ethyl sulfate, phosphatidyl ethanol, and carbohydrate-deficient transferrin as biomarkers of drinking and summarizes research dealing with their application in patients with alcohol use disorders who are candidates for or recipients of liver transplantation. The article also offers suggestions for enhancing the reliability of self-report measures of drinking status.

Sensitive and comprehensive client assessment entails complex conceptual and methodological considerations. Such activity is at the heart of matching clients to appropriate treatments. This article begins by specifying the goals and functions of assessment to support matching. This is followed by a discussion of the strategies employed in Project MATCH to identify matching and outcome variables. The assessment battery used in Project MATCH is next described. Finally, an overview of issues surrounding administration of assessment measures is provided. Particular attention is given to the topics of sequencing and timing of measures.

During the past 20 years researchers have become increasingly interested in exploring the benefits of differential assignment of alcoholics to treatments based on client-specific characteristics, rather than searching for a single "most effective" intervention for all clients. Thirty-one empirical studies on "client-treatment matching" are reviewed, particularly from the perspective of how research methodology in this area has evolved. In addition, general observations are provided on how research methodology on this topic can be further enhanced. Finally, several promising interactions between client characteristics and particular interventions are noted, based on empirical studies to date.

A growing body of investigations demonstrate that elevated levels of carbohydrate-deficient transferrin (CDT) effectively distinguishes alcoholics recently consuming large amounts of alcohol from light social drinkers or teetotalers. Nevertheless, important questions still remain concerning the value of CDT as a more generalized marker of alcohol consumption. Most important, the nature of the drinking pattern, including quantity and frequency, necessary to raise levels of CDT significantly remains unclear. Neither has research convincingly demonstrated that CDT is as accurate a marker for women, young adults, or non-Caucasian ethnic groups as for White, middle-aged men. Whereas CDT might serve as a useful outcome measure in trials of alcoholism treatment effectiveness, current research suggests that CDT is of limited value in identifying problematic drinking in general medical or community settings in which a broad continuum of drinkers is represented. Combining CDT with other biochemical or self-report screening measures may, however, improve sensitivity in these contexts. At present, the most accurate laboratory technique to detect CDT seems to be isoelectric focusing. Additional research, however, is needed to resolve the issue of whether CDT is best quantitated as a simple value or if its ratio to total transferrin or non-CDT results in higher predictive validity.

Using items from the Composite International Diagnostic Interview, dimensionality of the alcohol dependence syndrome was assessed in clinical samples in the United States and Russia. In both groups, a single-factor model provided a high degree of goodness of fit thus demonstrating cross-cultural coherence of the construct. The item dealing with narrowing of the drinking repertoire is most disparate in each sample. Severity of alcohol consequences was moderately related to alcohol dependence in both samples. Demographic variables, however, correlated less with severity of consequences. After the effects of severity of dependence and demographics were removed, quantity/frequency of recent alcohol consumption did not contribute to severity of consequences. Country, however, remained a significant, but small, predictor of severity of alcohol consequences.

The clinical practice of alcoholism treatment can be enhanced by the judicious use of standardized psychometric instruments to characterize clients during the course of treatment. Knowledge of key behavioral, personality, and alcohol-specific factors will increase the clinician's ability to select the most appropriate treatment option, or, even if treatment options are limited, at least to develop a treatment plant with the patient's unique needs in mind. Monitoring of progress towards treatment goals can also be facilitated by the use of selected assessment tools. Seven examples of well-validated instruments are discussed, with suggestions on how data derived from them may be applied in the treatment planning process.

While extensive research has been conducted to determine internal and external stimuli for drinking by alcoholics, the topic of how demographic, diagnostic, and personality variables may relate to these precipitants is largely unexplored. This study suggests that stimuli to use alcohol or drugs differ partly as a function of diagnosis (alcohol dependence vs. concurrent alcohol and drug dependence). Age, education, and gender do not appear related to the stimuli in either diagnostic group. Personality characteristics of cognitive reflectiveness, impulse control, sociability, and intrapunitiveness, however, seem to be associated with certain classes of high risk stimuli.

No single treatment has emerged as effective for all persons diagnosed as alcoholics. "Patient-treatment matching" is a method of choosing between alternative treatment options based on particular patient characteristics that interact differentially with interventions to produce more beneficial results than if "matching" had not been done. This review distinguishes three models for interactions between patient characteristics and interventions in terms of their clinical implications. Supporting empirical evidence for matching is also summarized. Requirements for the future research agenda are discussed and the pros and cons of implementing patient treatment matching in the clinical setting are addressed.

As part of the ground-based preparation for creating long-term life systems needed for space habitation and settlement, Space Biopsheres Ventures (SBV) is undertaking the Biosphere 2 project near Oracle, Arizona. Biosphere 2, currently under construction, is scheduled to commence its operations in 1991 with a two-year closure period with a crew of eight people. Biosphere 2 is a facility which will be essentially materially-closed to exchange with the outside environment. It is open to information and energy flow. Biosphere 2 is designed to achieve a complex life-support system by the integration of seven areas or “biomes” — rainforest, savannah, desert, marsh, ocean, intensive agriculture and human habitat. Unique bioregenerative technologies, such as soil bed reactors for air purification, aquatic waste processing systems, real-time analytic systems and complex computer monitoring and control systems are being developed for the Biosphere 2 project. Its operation should afford valuable insight into the functioning of complex life systems necessary for long-term habitation in space. It will serve as an experimental ground-based prototype and testbed for the stable, permanent life systems needed for human exploration of Mars.

Several earlier studies have reported clinically relevant personality correlates of high vs low scores on the MacAndrew Scale ( Mac) of the MMPI. Unfortunately, these projects have not adjusted for age or nature of abuse. Also, most have assumed that the personality correlates are the same for female patients as for male patients. This study attempts to address these deficiencies. Even after correcting for age and diagnosis, high Mac patients differ from low Mac patients on major scales of the MMPI. The pattern of such differences varies considerably between men and women. Substance abuse treatment implications of these differences are discussed.

This article summarizes content proceedings of a symposium held at the 2004 Research Society on Alcoholism Scientific Annual Meeting in Vancouver, Canada. The chairs were Friedrich M. Wurst and Raye Litten. The presentations were (1) Introduction, by Raye Litten; (2) Direct Ethanol Metabolites--On the Threshold From Science to Routine Use, by Friedrich M. Wurst; (3) Sialic Acid Index of Plasma Apolipoprotein J (SIJ) as a Viable Marker for Chronic Alcohol Consumption, by Philippe Marmillot; (4) The Emergence of Ethyl Glucuronide (EtG) Testing as a Tool in Monitoring Healthcare Professionals, by Gregory E. Skipper; (5) Application of Biomarkers for Alcohol Use Disorders in Clinical Practice, by Tim Neumann; (6) Utility of Biomarkers in Assessing the Efficacy of Medications for Treating Alcoholism, by Marty Javors; and (7) Discussion, by Raye Litten.

Aims: Physicians recovering from substance-related disorders are usually allowed to return to practice if they agree to remain abstinent from drugs, including alcohol, and to undergo random urine testing. Over 9000 physicians are currently involved in such monitoring programs in the US. To date, it has been difficult to adequately monitor abstinence from alcohol due to the short half- life of alcohol and no other highly specific marker. Ethyl glucuronide (EtG), a direct metabolite of alcohol, offers an extended window for assessment of drinking status (up to 5 days). Our aim was to assess the potential value of EtG testing in abstinence-based monitoring programs. Patients and methods: Urine samples were obtained from 100 participants in a physician monitoring program and additional samples were subsequently obtained 'for cause', 'to verify positive urine alcohol, when drinking was denied' and 'in high risk individuals'. All participants had signed contracts agreeing to remain abstinent from mood-altering drugs, including alcohol, and had agreed to random urine testing. EtG was determined using LC/MS-MS in addition to standard testing. The main outcome measure were urine specimens positive for EtG versus those positive based on standard testing for alcohol and other drugs. Results: Among the initial 100 random samples collected, no sample was positive for alcohol using standard testing; however, seven were positive for EtG (0.5-196 mg/l), suggesting recent alcohol use. Subsequent EtG testing was performed clinically during the course of monitoring. Of the 18 tests performed to date, eight of eight tests performed 'for cause' were positive for EtG but negative for all other drugs including urine alcohol. All eight were confirmed positive by self reported drinking by the patient when confronted regarding the positive test result. Of six tests performed to 'confirm a positive urine alcohol' two were positive for EtG and confirmed positive by self reported drinking. For the other four samples, especially as two are from a diabetic, in vitro fermentation of ethanol is discussed. Conclusions: These data suggest that physicians in monitoring programs have a higher rate of unrecognized alcohol use than previously reported. Incorporation of EtG testing into alcohol abstinence monitoring can strengthen these programs.

Aims: In a variety of clinical and forensic situations long term use of alcohol must be monitored. In this project we explore the utility of fatty acid ethyl esters (FAEE) in this regard. Additionally, we propose a cut-off value of FAEE to distinguish teetotallers/moderate/social drinkers from alcoholics or individuals drinking at harmful levels. Patients and methods: FAEE levels from 18 alcohol-dependent patients in detoxification were contrasted with those of 10 social drinkers and 10 teetotallers. FAEE in hair were determined, using headspace solid phase microextraction and gas chromatography mass spectrometry. C FAEE , as sum of the concentrations of four esters, was compared to a major FAEE, ethyl palmitate. PEth was measured in heparinized whole blood with a high pressure liquid chromatography (HPLC) method. Drinking validation criteria include self reports, phosphatidyl ethanol (PEth) in whole blood as well as the traditional markers of heavy drinking, gamma glutamyl transpeptidase (GGT), mean corpuscular volume (MCV) and carbohydrate deficient transferrin (CDT). Results: Receiver-operating characteristic (ROC) curve analysis for C FAEE , indicated a sensitivity of 100% and a specificity of 90% for a cut-off of 0.29 ng/mg. By using a cut-off of 0.4 ng/mg, CFAEE identified 94.4% correctly. C FAEE and ethyl palmitate were significantly associated (r = 0.945; P < 0.001) as were C FAEE and PEth (r = 0.527; P = 0.025). No significant correlation was found between CFAEE and total grams of ethanol consumed last month, blood-alcohol concentration at admission to the hospital, CDT, MCV, or GGT. Among the serum and blood markers, %CDT identified 47.1%, MCV 38.8% and GGT 72.2% of patients with chronic intake of higher amounts of ethanol correctly, whereas PEth achieved 100% accuracy. Conclusions: The data suggest that C FAEE is a potentially valuable marker of chronic intake of high quantities of ethanol. Furthermore, the results indicate that a reasonable and provisional FAEE cut-off to distinguish between social/moderate and heavy drinking/alcoholism in hair is 0.4 ng/mg.

Several biochemical tests are available to screen for heavy drinking in patients. Most of these (e.g., liver function tests and macrocytic volume) rise due to adverse effects of alcohol on organs or the organ's functions. Carbohydrate-deficient transferrin, however, seems to elevate because of the direct action of alcohol or one of its metabolites. A second valuable contribution of biomarkers is identification of relapse events in recovering alcoholics that either would not be voluntarily reported or reported only much later. Finally, providing feedback to patients in treatment based on their biomarker values and changes in them during the course of treatment can enhance motivation, a key component in recovery from alcohol problems. The current article offers a clinical rationale for routine use of biomarkers of heavy drinking in health care practice and proposes recommendations on how they might be best used.

Since return to drinking is common in patients recovering from alcoholism, recognition of relapse should be an important component of treatment. Recurrent assessment with biochemical measures can provide clinicians with useful information on the drinking status of their patients. This chapter addresses issues surrounding the importance of early detection of relapse, describes biochemical markers that may assist in this, reviews relevant scientific investigations, and offers recommendations to researchers and clinicians.

Noteworthy advances have been made in methods of assessing patients suffering alcohol problems. More than one hundred measures are now available to assist clinicians and researchers in screening for such problems, diagnosing them, and developing treatment plans individualized according to relevant patient characteristics. This chapter reviews progress in assessment supporting each of these activities and suggests directions for future research. It concludes by identifying a series of research issues that cut across multiple domains of alcohol assessment.

For humans to survive during long-term missions on the Martian surface, bioregenerative life support systems including food production will decrease requirements for launch of Earth supplies, and increase mission safety. It is proposed that the development of “modular biospheres”- closed system units that can be air-locked together and which contain soil-based bioregenerative agriculture, horticulture, with a wetland wastewater treatment system is an approach for Mars habitation scenarios. Based on previous work done in long-term life support at Biosphere 2 and other closed ecological systems, this consortium proposes a research and development program called Mars On Earth™ which will simulate a life support system designed for a four person crew. The structure will consist of 6 × 110 square meter modular agricultural units designed to produce a nutritionally adequate diet for 4 people, recycling all air, water and waste, while utilizing a soil created by the organic enrichment and modification of Mars simulant soils. Further research needs are discussed, such as determining optimal light levels for growth of the necessary range of crops, energy trade-offs for agriculture (e.g. light intensity vs. required area), capabilities of Martian soils and their need for enrichment and elimination of oxides, strategies for use of human waste products, and maintaining atmospheric balance between people, plants and soils.

An isocratic HPLC procedure for the assessment of thiamine (T), thiamine monophosphate (TMP) and thiamine diphosphate (TDP) in human erythrocytes is described. Several aspects of the procedure make it suitable for both clinical and research purposes: limits of detection and quantification of 1 and 2.5 nmol/l, respectively, recovery of 102% on average (range 93-112%), intra- and inter-day precisions within 5 and 9%, respectively, total elution time 15 min. This analytical methodology was applied to a case-control study on erythrocyte samples from 103 healthy subjects and 36 alcohol-dependent patients at risk of thiamine deficiency. Mean control values obtained were: T=89.6+/-22.7 nmol/l, TMP=4.4+/-6.6 nmol/l and TDP=222.23+/-56.3 nmol/l. T and TDP mean values of alcoholics were significantly lower than those of control cases: T=69.4+/-35.9 nmol/l (P

Efficient, inexpensive screening for early stage alcohol problems is important in health care settings. The Alcohol Use Disorders Identification Test (AUDIT) has been studied extensively to establish its value in this regard.A literature search that used EtOH as a database was conducted to identify studies published on the AUDIT through September 2001. Keywords used for the search were "Alcohol Use Disorders Identification Test" and "AUDIT." All studies reporting psychometric properties of the measure were reviewed with particular attention being given to the period 1996 and later. A small number of additional references were located by noting their citation in other studies reviewed.Although more research is needed on non-English versions to establish their psychometric properties, at least in its English edition, the AUDIT demonstrates sensitivities and specificities comparable, and typically superior, to those of other self-report screening measures. Test-retest reliability and internal consistency are also quite favorable. For males, the AUDIT-C, a shortened version of the AUDIT, appears approximately equal in validity to the full scale.Recent research continues to support use of the AUDIT as a means of screening for alcohol use disorders in health care settings in the United States.

Background. Misuse of alcohol is associated with a range of medical problems. Fortunately, a simple pencil-and-paper measure, the Alcohol Use Disorders Identification Test, can effectively and efficiently screen for early-stage alcohol abuse as well as provide the physician information that can assist in brief intervention. Objective. The objective of this article is to briefly summarize research published on the Alcohol Use Disorders Identification Test and suggest its potential role in brief intervention in primary care settings. Methods. Scientific literature on the Alcohol Use Disorders Identification Test though 2000 was reviewed and synthesized to address issues relevant to use of the test in primary health care settings. Results. The Alcohol Use Disorders Identification Test is quite sensitive and specific and compares favorably with alternative self-report screens for alcohol problems.

The relationships of carbohydrate-deficient transferrin (CDT), gamma-glutamyltransferase (GGT) and their mathematical combination (gamma-CDT) with self-reported diseases were evaluated in a large cross-sectional risk factor survey. Significant gender effects were observed in associations of the markers with several medical conditions as well as with general health care utilization. In men, CDT was associated with rheumatoid arthritis. In both genders, GGT was positively associated with hypertension and diabetes. gamma-CDT was positively associated with hypertension in males and with asthma in females. This general population study demonstrates that these markers, although most commonly used to assess alcohol misuse, might also serve as health risk indicators.

Although assessment in the field of alcoholism treatment is generally verbal in nature, biological tests can also provide counselors and program evaluators useful and unique information. Five such laboratory measures are briefly described, with particular emphasis on carbohydrate deficient transferrin, a biomarker recently approved by the FDA. Applications for laboratory tests in alcohol screening, motivating patients, and monitoring treatment progress are also proposed.

The dose response to alcohol use of carbohydrate-deficient transferrin (CDT), gamma-glutamyltransferase (GGT), and their combination (gamma-CDT) was studied in an age- and gender-stratified, random sample from Finland in 1997. A linear association with a threshold between alcohol consumption and the three markers was observed. Body mass index was negatively associated with CDT and positively with GGT Age was positively associated with GGT and gamma-CDT In conclusion, CDT appears to be an early phase marker of alcohol consumption. The combined marker, gamma-CDT, was less associated with factors such as body mass index but more strongly correlated with alcohol consumption than were the two markers separately.

Whereas heavy alcohol consumption is known to elevate serum carbohydrate-deficient transferrin (CDT) and gamma-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.

Over the past decade, research on medications to treat alcohol problem has flourished. Naltrexone and acamprosate are tangible fruits of such endeavors and each has now earned approval in a large number of countries. Recent studies on naltrexone indicate that patient compliance is important if full benefits are to be achieved. Several laboratory studies with human subjects are beginning to elucidate the mechanisms underlying efficacy of naltrexone, as well as explaining variability of response among subpopulations of drinkers. In addition to these two agents, recent investigations have also demonstrated that the antidepressants desipramine, imipramine, and fluoxetine reduce mood-related symptoms and, to some extent, drinking itself in alcoholics who are depressed. Research to date suggests that opioid antagonists and selective serotonin reuptake inhibitors are more effective in reducing alcohol intake when used in combination. Clinical issues, methodology, and directions for future research are also reviewed in this article. In particular, issues addressed include alternative dosage regimens, necessary duration of treatment, employment of medications in combination, integration of pharmacologic agents with behavioral interventions, enhancement of patient compliance, and concurrent treatment of psychiatric comorbidity.

Both gamma-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.

Multisite clinical trials have two major advantages over single-site studies: the large sample size of multisite studies allows for adequate statistical power and better representativeness of the population being studied. However, they are more complex to implement than single-site studies. This article reviews previous multisite clinical trials of alcohol abuse and alcoholism, reasons for selecting a multisite design, management of such studies, and some statistical issues.

This project explores the cross-national construct validity of the Alcohol Dependence Syndrome. The investigation also examines basic psychometric properties of the Alcohol Dependence Scale (ADS), an instrument commonly employed to measure dependence. Subjects consisted of inpatients and outpatients in American and Russian alcoholism treatment programs. Despite some variations, an orthogonal four factor structure of the ADS appears similar across the two cultural samples, thus lending support to the alcohol dependence construct. Analyses of psychometric properties of the Scale generally support its value in future cross-cultural research on alcohol dependence.

Sensitivities, specificities, and odds ratios for hazardous drinking for various cut scores on the CAGE are computed for a large sample active duty Army personnel. Contrasts on these properties are made between the standard CAGE and a "modified CAGE" consisting of standard CAGE items and two other items dealing with problematic drinking. The role of demographic variables--gender, ethnicity, marital status, rank category, and age in mediating relationships of both versions of the screening test to hazardous drinking--is also explored. At a cutoff score of one endorsed item, odds ratios were highest for female personnel and commissioned officers. Language: en

Pharmacodynamic benefits of disulfiram in the treatment of alcoholism have yet to be clearly demonstrated. Nevertheless, research does suggest that disulfiram may well have positive effects on drinking if medicational compliance procedures are employed. This paper reviews research on four strategies for enhancing disulfiram compliance: implants, incentives, contracts, end patient information. Generalizations about the strategies are drawn and needs for future research are briefly addressed.

Constructed in 1986, the Biosphere 2 Test Module has been used since the end of that year for closed ecological systems experiments. It is the largest closed ecological facility ever built, with a sealed variable volume of some 480 cubic meters. It is built with a skin of steel spaceframes with double-laminated glass panels admitting about 65 percent Photosynthetically Active Radiation (PAR). The floor is of welded steel and there is an underground atmospheric connection via an air duct to a variable volume chamber (“lung”) permitting expansion and contraction of the Test Module's air volume caused by changes in temperature and barometric pressure, which causes a slight positive pressure from inside the closed system to the outside thereby insuring that the very small leakage rate is outward. Several series of closed ecological system investigations have been carried out in this facility. One series of experiments investigated the dynamics of higher plants and associated soils with the atmosphere under varying light and temperature conditions. Another series of experiments included one human in the closed system for three, five and twenty-one days. During these experiments the Test Module had subsystems which completely recycled its water and atmosphere; all the human dietary needs were produced within the facility, and all wastes were recycled using a marsh plant/microbe system. Other experiments have examined the capability of individual component systems used, such as the soil bed reactors, to eliminate experimentally introduced trace gases. Analytic systems developed for these experiments include continuous monitors of eleven atmospheric gases in addition to the complete gas chromatography mass spectrometry (GCMS) examinations of potable, waste system and irrigation water quality.

The past 10 years have witnessed important advances in research on pharmacotherapy for alcoholism. Promising drugs are discussed under six headings: agents to treat alcohol withdrawal; anticraving agents; agents that make drinking an aversive experience; agents to alleviate concomitant psychiatric problems; agents to treat concurrent drug abuse; and amethystic (“sobering-up”) agents. Research on the drug classes is summarized and clinical issues surrounding specific agents and alcoholism pharmacotherapy in general are discussed. Finally, long-range therapeutic implications of recent findings on the actions of alcohol on basic mechanisms of the brain are offered.

✓ The pituitary function of two patients with acromegaly was monitored before, during, and after selective transnasal pituitary adenomectomy. The purpose of the study was to verify the efficacy of this technique, and to see if there was normal function in the residual pituitary tissue. Following surgery, both patients showed clinical improvement with no evidence of significant anterior or posterior pituitary dysfunction. Concentrations of plasma growth hormone obtained serially during surgery were elevated prior to tumor removal but fell precipitously after adenomectomy. The half-life for immunoreactive growth hormone in these patients was less than 35 minutes. We conclude that selective transnasal pituitary adenomectomy is an effective treatment for pituitary tumors. Furthermore, our data suggest that the pituitary tumor in these patients did not arise because of excessive stimulation by hypothalamic growth hormone-releasing factor.

The alcoholism treatment service delivery system is described in terms of facility characteristics, funding, and demographics of clientele served. A brief discussion of the "Minnesota Model," the most pervasive therapeutic approach to alcoholism in the United States is then offered. The article concludes with a synopsis of key research findings and current public debate issues which may impact the future delivery of treatment services to alcoholics.

Melatonin levels exhibited a day-night rhythm with highest levels at night. Nocturnal plasma melatonin concentrations were unrelated to sleep stages, whereas secretion of GH was temporally related to slow wave sleep. Levels of corticotropin rose in the later sleep cycles. We found no relationship between endogenous nocturnal melatonin and adenohypophyseal hormone levels. The results indicate that in young men nocturnal levels of melatonin are controlled separately from those of LH, PRL, corticotropin, and GH.