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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

The past decade has witnessed major advances in understanding of neural functioning and neurobiological bases of alcohol consumption. Concurrent with this, a range of exciting investigations have been conducted on pharmacologic agents that may curb drinking behavior. Research is reviewed on several promising medications influencing neurotransmitter and endocrine systems with particular attention to the serotonergic and opioid systems. Following this overview, recommendations are offered regarding research methodology to support future pharmacotherapy trials.

Alcoholism is an exceedingly common and serious problem in our society. State-of-the-art estimation procedures place the number of alcohol-dependent persons in the United States at approximately 9 million with an additional 6 million persons diagnosable as nondependent alcohol abusers. Alcohol abuse and alcohol dependence are most prevalent among younger males. For both genders these problems tend to decrease with age (Williams, Grant, Harford, & Noble, 1989).

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.

Transferring the results of scientific research into practical applications that benefit society has been and continues to be a challenging task.Technology transferis one term used to describe this process. This term was coined to refer to incorporating technology developed for the space program into useful consumer products. Another commonly used term isknowledge utilization.These terms are used interchangeably throughout this chapter. Technology transfer or knowledge utilization is probably performed most effectively in the field of agriculture. Historically, agricultural technology transfer has its modern beginnings in the 1920s with efforts to disseminate agricultural science to farmers.1

The past 10 years have witnessed dramatic growth in alcoholism research. In particular, attention has been focused intensely on techniques that diagnose and treat alcoholism more effectively. The evolution and expansion of this important area is reflected by the fact that in 1990, the National Institute on Alcohol Abuse and Alcoholism, the major funding source for alcoholism research in the world, expended over $22 million on investigations primarily oriented toward treatment issues, whereas the comparable figure a decade earlier was below $2 million. In light of the magnitude as well as the economic and personal cost of alcoholism, public support for research on treatment is likely to be sustained and, in fact, strengthened in the future.

The past decade has witnessed a burgeoning of pharmacotherapy research directed toward the resolution of acute and chronic problems with alcohol. Because of the multifaceted nature of alcohol abuse and alcoholism, a correspondingly wide range of possible medications are being actively investigated, and several show promise in managing the diverse alcohol-related problems that present in clinical practice.(SeeLitten and Allen1for review.)

This chapter offers a general summary and perspective on measures of alcohol consumption. In it, we address five issues: 1. Differences between verbal and biochemical techniques to assess alcohol consumption, 2. Features that are desirable in measures of consumption, 3. Comparisons of specific techniques according to these standards, 4. Possible strategies for measuring consumption in various settings, and 5. Needs for further research.

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.

Considering the prevalence of excessive alcohol use, its adverse consequences on physical and emotional well-being, and the high degree of responsivity of early-stage drinking problems to brief intervention, screening for alcohol abuse is warranted in medical practice. We describe several practical self-report tests that can help primary care physicians screen their patients for alcohol abuse. Two of the more popular tests, the Michigan Alcoholism Screening Test and the CAGE (an acronym for questions about cutting down on drinking, annoyance at others' concern about drinking, feeling guilty about drinking, and using alcohol as an eye-opener in the morning), are comparable in sensitivity and specificity. Either test is appropriate, but the brevity of CAGE generally gives it an advantage in a busy medical office. Three new tests, the Alcohol Use Disorders Identification Test, the Adolescent Drinking Index, and the TWEAK also are promising. We offer guidelines for selection of screening tests for primary care practice. (Arch Intern Med. 1995;155:1726-1730)

✓ 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.

The Institute of Ecotechnics operates its projects in seven countries and on a ship that voyages the tropic oceans, the Mediterranean, and the Amazon. Fourteen associates initially founded the Institute with a capital of US$ 25 000 to make the down payment and start up operations on a badly eroded ranch in New Mexico in 1969, with the purpose of beginning and developing a new discipline; interrelating ecosystems, including man, his cultures, and his technosphere with the evolving biospheric totality on the planet earth. In addition they forwent all pay for the first year, an equivalent of over US$ 200 000. The initial associates included an MBA entrepreneur engineer, an artist, a dancer, the former Head of the Computer Users Consultancy Department of Lawrence Radiation Laboratory, a philosopher, a chemist, a communicat ions technician, a union organizer, and an AIA a rch i t ec t s tuden t of Frank Lloyd Wright and Bruce Goff, and five young 'all-rounders', all ready to commence the endeavor of creating the beginning of the new discipline seen as critical for themselves personally, their society, and for Nature.

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.

SUMMARY In order to define nyctohemeral plasma ACTH secretory patterns, frequent plasma ACTH samples were obtained in seven patients with untreated Cushing's disease (i.e. pituitary-dependent Cushing's syndrome), five Cushing's patients treated by bilateral adrenalectomy, four of whom had Nelson's syndrome, and one patient with 21-hydroxylase deficiency (congenital adrenal hyperplasia). A nyctohemeral rhythm of plasma ACTH concentration was apparent in the one patient with the adrenogenital syndrome but not in those with Nelson's syndrome or Cushing's disease. The effect of graded doses of dexamethasone, 2, 8 or 32 mg per 24 h period, on plasma ACTH concentrations was studied in patients with untreated or treated Cushing's disease or Nelson's syndrome. In all of these hypercorticotrophic states, the mean plasma ACTH concentration was not significantly affected by the smallest dose of dexamethasone, was partially suppressed by the intermediate dose, and further suppressed by the largest dose. In contrast, the patient with congenital adrenal hyperplasia and elevated plasma ACTH concentrations showed complete suppression of plasma ACTH levels following the smallest dose of dexamethasone. These findings indicate that there is resistance to ACTH suppression by dexamethasone in all stages of Cushing's disease and suggest that negative feedback of glucocorticoids may be involved in the pathogenesis of this disease.

(1) The nocturnal rise in plasma melatonin concentration continued through two cycles with continuous light occlusion by blindfolds in normal subjects. A daytime nap did not disturb the rhythm. (2) The plasma melatonin rhythm was present in patients with pituitary-adrenal and pituitary-gonadal failure, but appeared diminished or absent in patients bearing lesions at different points in the pineal afferent pathway. (3) In other patients and subjects who showed normal response of cortisol, growth hormone or prolactin after stimuli including hypoglycemia, pneumoencephalography, exercise or administration of l -dopa during the daytime, there was no stimulation of plasma melatonin concentration. (4) Melatonin was not correlated with prolactin in blood or cerebrospinal fluid of patients with a wide range of plasma prolactin levels. (5) The adult human melatonin rhythm is relatively independent from pituitary, gonadal, and adrenal function, but may rely on a neural pathway similar to that controlling the rhythm in lower animals. The human melatonin rhythm may represent the output of a stable oscillator with a signal relatively free from acute perturbation by sleep, darkness, or stress sufficient to cause changes in other hormones.

The circadian secretion of ACTH and corticosterone was assessed by measuring immunoreactive ACTH concentration in the plasma and ACTH content in the anterior and posterior pituitary over a 30 h period in groups of both male and female rats and comparing these data to fluorometric corticosterone concentration in the plasma and corticosterone content in the adrenal. A circadian rhythm of plasma corticosterone levels and adrenal content was apparent in both males and females with the highest levels at the onset of darkness. In contrast, there was no significant circadian rhythm in plasma ACTH levels or anterior or posterior ACTH pituitary content. Because the ACTH and corticosterone rhythms were dissociated, rhythmic corticosterone secretion is not entirely dependent on ACTH secretion.

In 35 daytime paired blood and cerebrospinal fluid (CSF) samples from 15 patients, melatonin levels in CSF were undetectable or detectable but not higher than blood levels. During pneumoencephalography in 6 patients, no significant elevation of blood melatonin levels was observed, whereas cortisol concentration increased.

Two methods for arriving at optimum, individual phenytoin dosage regimens have been evaluated in 12 patients. (1) Individual Michaelis-Menten pharmacokinetic parameters for phenytoin were estimated from two reliable steady-state phenytoin serum concentrations resulting from different daily doses: The observed steady-state phenytoin serum levels obtained after 3 to 8 wk of compliance with dosage regimens calculated from the individual pharmacokinetic parameters agreed well with predicted levels (r = 0.824, p less than 0.02). The average deviation between observed and predicted levels was 0.04 mug/ml (range, +/- 3.2 mug/ml). (2) A previously published nomogram for making adjustments in phenytoin dosage regimens: The serum phenytoin concentration actually expected from the dose indicated by the nomogram was calculated using individual pharmacokinetic parameters. The daily dose for one patient would have exceeded his estimated maximal rate of metabolism. The correlation between calculated and predicted phenytoin serum levels in the other 11 patients was weak but significant (r= 0.360, p less than 0.05). The average deviation was --3 mug/ml (range, 3.9 to --11.3 mug/ml). It was concluded that the use of individual pharmacokinetic parameters is practical and is also superior to the nomogram.

A previous report of the presence of ACTH in cerebrospinal fluid (1) prompted an investigation of its concentration in the CSF of patients with nonendocrine disease and of the mechanism by which it enters this fluid. The mean immunoreactive ACTH concentration in 22 patients was 98 pg/ml which slightly, but not significantly, exceeded the mean concentration in simultaneously obtained plasma specimens (74 pg/ml). However, there was no correlation (r = 0.2) between the concentrations of individual pairs of ACTH values obtained from plasma and CSF. The transport of ACTH between the blood and CSF compartments was investigated in man and the cat. After 48 hr administration of exogenous ACTH in man, when the plasma concentration was very high, the CSF ACTH concentration remained low. During infusion of labeled ACTH in cats, a steadystate plasma/CSF radioactivity ratio was obtained after 4–6 hr, at which time the concentration of radioactivity attributable to labelled ACTH was 100 times higher in plasma ...

Recent findings in the area of interactions among alcohol, opiates, and opiate receptors are reviewd. In the laboratory animal, alcohol dependency is associated with an increased intake of morphine as well as an increased sensitivity to morphine toxicity. Acute administration of alcohol is associated with elevations of plasma β-endorphin similar in magnitude to that seen with acute morphine administration. Opiate antagonists can precipitate alcohol and other central nervous system depressants. These data support the clinical observations of alcohol-opiate interactions in narcotic addicts as well as explain the increased morbidity seen with concurrent alcohol use in persons on methadone maintenance.

SummaryComplete or anterolateral, but not anterior, basal hypothalamic deafferen-tation prevented the increased basal secretion of ACTH in chronically adrenalecto-mized rats. ACTH secretion in response to ether stress was at least as great in the de-afferented, adrenalectomized rats as in intact controls. The data suggest that extra-hypothalamic influences which enter the lateral basal hypothalamus are necessary to achieve a high basal ACTH secretion when plasma ghicocorticoids are depressed.

Adaptation to a repeated stress in male rats was studied by measuring plasma ACTH by radioimmunoassay 2.5 min or plasma corticosterone by acid fluorescence 20 min alter initiation of the stress. No adaptation was seen in the secretion of ACTH in response to ether, tourniquet, or leg-break stresses repeated at 90 min intervals 1–3 times. A marked rise in plasma ACTH concentration was produced within 2.5 min after application of each stress. Plasma ACTH always returned to basal levels by 90 rain after application of stress. Ether stress repeated at 24-hr intervals for 3 days did not produce any decrease in either the plasna ACTH or corticosterone response by the third day. These data indicate that no adaptation in ACTH secretion in response to repeated stress occurs under the conditions of our experiments.

The endocrine function in a fullterm 2.1 kg female anencephalic infant was studied by measuring immunoreactive ACTH, growth hormone, insulin, TSH, T4, and T3 concentrations in umbilical cord blood and serial venous plasma samples obtained at 10–30-min intervals until death. In addition, plasma cortisol and T4 concentrations were determined by competitive protein binding. The following materials were given: TRF (100 mg, iv) at 86 mins; lysinevasopressin (LVP) (2.5U, iv) at 125 mins; α1-24 ACTH (1 mg, im) at 160 min; and TSH (5U, im) at 221 min. Plasma TSH and ACTH concentrations were low in the infant until stimulation by TRF and LVP, respectively. Plasma TSH and ACTH concentrations then increased significantly. There were no corresponding changes in plasma T4, T3, or cortisol concentrations following the elevation in plasma TSH and ACTH concentration. A spike in plasma insulin concentration occurred following injection of vasopressin with a subsequent fall in the plasma glucose concentration. The...

This experience with strokes induced by hyperventilation during repose in patients with SS is presented to caution against its use in patients with SS. We have discontinued hyperventilation during EEC in all of our patients with SS. Cheatham and Brackett12 and Richards and Nulsen13 state that the risks of angiography in patients with SS are significant. However, Stockman et al. have recently demonstrated that with repeated exchange transfusion preparation, angiography can be carried out without incident. Even so, we did not feel these patients were surgical candidates; therefore, angiography was not performed. If further experience with hypertransfusion should prove effective in producing clinical and functional neurological improvement, angiography would be a useful tool in following the course of the vascular disease. Certainly, the angiographic reversal of the vascular disease would suggest that hypertransfusion may be helpful in patients with SS who have had transient cerebral episodes.

During the past twenty-five years much research has dealt with the factorial structure of measures of mental ability among groups of American children differing in ethnicity and socio-economic status. These investigations are relevant to determining the fairness and appropriateness of general mental ability tests when employed with minority or economically deprived children. In fact, general employment of these tests is predicated on the assumption that they measure the same factors of ability in all students. For the most part studies suggest that test factorial structure is unaffected by ethnic or socio-economic differences (Mitchell, 1956; Osborne, 1963, 1964; McGaw & Joreskog, 1970; Wasik & Wasik, 1970; Silverstein, 197 3; Kaufman & Hollenbeck, 1974; Kaufman & Di Cuio, 1975; Reschly, 1978; Mishra, 1981). Only two studies report some faccorial variation. Semler and Iscoe (1966) found that while both white and black children under 10 yr. of age show a comparable verbal comprehension factor on the Wechsler Intelligence Scale for Children, they differ on two other test factors. In a project of extreme interest to us because it also employed the Iowa Tests of Basic Skills, Thornson, Alston, and Say (1978) noted some factorial incongruity across Anglo, black, and Mexican-American sixth graders. Unfortunately, this effort was flawed in several respects such as very small Ns for the item-by-item factor analyses, retention of a large number of factors (36f) apparently solely on the basis of statistical rather than conceptual considerations, and failure to modify the Kaiser rule-of-thumb congruence index of .85 suggesting factorial similarity across groups (Kaiser, Hanka, & Bianchini, 1969), by mitigating parameters such as the number of subjects, number of factors, and number of underlying test items (see Korth & Tucker, 1975). While the bulk of research argues for factorial similarity of measures of mental ability across groups of children of varying ethnicity and socio-economic status, no past investigations were found which looked at the invariance of cog

Various levels of lower body negative pressure (LBNP) were applied to human volunteers and plasma ACTH and Cortisol levels measured. There were no significant alterations in plasma ACTH and Cortisol concentrations suggesting that LBNP is a mild stressor.