bluuebunny/crossref_metadata_2025 huggingface dataset:
A Critical Overview of Evaluations of Alcoholism Treatment
Authors: Mandell Wallace
Published: February 2008

Most alcoholism treatment evaluations do not use adequate evaluation research designs or an adequate array of outcome measures whose reliability and validity have been established. Data about the durability of treatment effects are also missing. As a result, many evaluation study findings are open to question. Measures of alcohol addiction, general morbidity, and mortality are proposed as essential in evaluating treatment effects, along with the more usual reports of work and criminal history. Estimates of quantity and frequency of alcohol consumption are deemed preferable to current categorizations of alcohol consumption after treatment into moderate or heavy drinking. A large proportion of alcoholics who seek treatment seem to do well even when they do not continue in it. The type of treatment provided does not seem to improve chances of success. Lifestyle and community factors are probably influencing outcomes of treatment; however, these have not been taken into account in most studies. Attempts to improve treatment program management by evaluation studies hold promise. Review by professional standards, management by exception, and cost effectiveness studies have been undertaken in isolated instances. Several cost effectiveness indicators for state alcoholism and treatment programs are proposed for use with available data.
Benefit‐Cost Methodology in the Evaluation of Therapeutic Services for Alcoholism
Authors: Rundell O.H. , Paredes Alfonso
Published: February 2008

Benefit‐cost analysis as a form of “social profitability analysis” can be a powerful tool in the overall evaluation of alcoholism treatment efforts. Alcoholism treatment potentially leads to a multiplicity of benefits in addition to sobriety. Benefit‐cost analysis provides a methodology for converting many of these diverse benefits into a common metric (dollars). thereby allowing the comparison of aggregate benefits and treatment costs. The analysis thus leads to the expression of treatment outcome in terms of the return on investment. A benefit‐cost analysis conducted on 3034 clients from the Oklahoma data base indicated a return to society of $1.98 for every $1 invested in alcoholism treatment. Such data may represent a critical portion of the information required for responsible resource allocation decisions.
Life‐Table Analysis of Treatment Outcome Following 185 Consecutive Alcoholism Halfway House Discharges
Authors: A.C.S.W. Jacquelyn Dwoskin , Gordis Enoch , Dorph Douglas
Published: February 2008

We define a halfway house as a transitional residence where patients learn skills and acquire confidence to function independently after discharge to a noninstitutionalized setting. Accordingly, our residents are provided shelter, food, counseling, group therapy, and medical care, but are expected to do assigned housework, attend AA, take disulfiram, obtain outside work, pay some rent, and find a place to live. The life‐table method examines outcome for all patients seen up to the time of analysis and allows for different lengths of time that patients are known to the program. With this method, we calculated probability of not drinking (“survival“) for successive 2‐mo intervals after discharge from the house, based on the fate of all 185 patients known to us in August 1977. At least 101 patients drank during the first 2 mo. Cumulative probabilities of abstinence were 0.37 at 2 mo, 0.28 at 4 mo, 0.21 at 6 mo. and 0.19 for several months thereafter. Survival curves calculated for subsets of the population were similar when we classified for race, sex, prior inpatient rehabilitation, or employment at discharge. Patients older than 40 did slightly better. We conclude that (1) most patients will do well while in a sheltered environment, no matter what it is called, and (2) social rehabilitation itself does not produce sobriety. We will prevent relapses more effectively only when we better understand the physiology of alcohol hunger.
Alterations in Neurotransmitter Activity After Acute and Chronic Ethanol Treatment: Studies of Transmitter Interactions
Authors: Hunt Walter A. , Majchrowicz Edward , Dalton Thomas K. , Swartzwelder H. S. , Wixon Henry
Published: February 2008

Acute and chronic ethanol treatment has multiple effects on the neurotransmitter systems in the nigrostriatal complex. A single dose of ethanol increases striatal dopamine release at low doses, but depresses it at high doses. In ethanol‐dependent rats, dopamine release is accelerated during intoxication, but is reduced during a withdrawal syndrome. Concomitantly, high‐affinity choline uptake, an index of cholinergic activity, is elevated at times when dopamine release is depressed. Changes in dopaminergic or cholinergic receptor activity do not induce or result from these effects. Neither has a role for GABA or substance P yet been implicated. The data suggest that interactions between at least two transmitters in the caudate nucleus may occur after acute and chronic ethanol treatment.
Interaction of Salsolinol and Tetrahydropapaveroline with Catecholamines
Authors: Melchior Christine L.
Published: February 2008

Formation of aberrant amine metabolites, tetrahydroisoquinolines (TIQs), has been hypothesized to account for some of the effects of ethanol. These compounds have been shown to interact with catecholamine neurons in a variety of ways by in vitro techniques. The most interesting facet of these alkaloids, however, is the fact that they cause an increase in preference for and voluntary consumption of ethanol when administered into the ventricle of the rat in exceedingly low amounts. Investigation of the neurochemical effects in vivo of two of the TIQs, tetrahydropapaveroline (THP) and salsolinol, indicates that they influence several aspects of presynaptic catecholamine function when examined acutely. The mechanism of action responsible for the radical long‐lasting behavioral effects of these substances has yet to be defined.
Pharmacokinetics of Ethanol: A Review
Authors: Wilkinson PaulK.
Published: February 2008

The pharmacokinetics of ethanol in man are reviewed from a historical perspective from the earliest attempts at kinetic analysis of urinary data in 1899 to the present nonlinear analysis of blood alcohol concentration (BAC) and time data. Review of the various kinetic theories that have been utilized to describe the kinetics of alcohol metabolism is provided. Extensive review is made of recent investigations supporting the application of Michaelis‐Menten enzyme kinetics to describe alcohol metabolism. Results of direct, nonlinear least‐squares computer fitting of BAC following intravenous and oral feeding of alcohol both in the fasting and fed states are presented with appropriate theory. The kinetics of the oral absorption of alcohol and the relationship among stomach emptying rate, the apparent absorption rate, and the area under the BAC‐time curve are discussed and data presented. The kinetics of multiple Michaelis‐Menten pathways are discussed with application to the (potential) contributions of the MEOS and/or ADH systems to the observed BAC curve and resultant kinetic parameters. Several methods of obtaining pharmacokinetic (Michaelis‐Menten) parameters from BAC curves and their interpretation and usage in comparative studies are presented.
The Effects of Acetaldehyde and Disulfiram on Albumin Synthesis in the Isolated Perfused Rabbit Liver
Authors: Rothschild Marcus A. , Oratz Murray , Schreiber Sidney S. , Mongelli Joseph
Published: February 2008

Acetaldehyde infusions inhibit albumin synthesis in the liver from fed donors but not in the livers from fasted donors. The inhibition of acetaldehyde metabolism with 4‐MP and disulfiram reverses this finding, suggesting that acetaldehyde per se is not the toxic agent. Disulfiram stimulates albumin synthesis in livers from fasted donors, and the presence of acetaldehyde does not prevent this process. The effects of ethanol infusions cannot be explained as due to the presence of acetaldehyde; some intermediate metabolic step may be the basis of the inhibition of albumin production and polysome disaggregation in the presence of ethanol.
Interaction of Sted‐eze, Nikethamide, Pipradrol, or Ammonium Chloride with Ethanol in Human Males
Authors: Alkana Ronald L. , Parker Elizabeth S. , Cohen Harry B. , Birch Herman , Noble Ernest P.
Published: February 2008

The central stimulants, pipradrol and nikethamide, the commercially available purported ethanol antagonist vitamin compound, Stedeze, and the acidifying diuretic, ammonium chloride, were tested for their efficacy in reversing acute ethanol intoxication in humans. Male moderate drinkers ingested ethanol (0.8 g/kg) and then either pipradrol (2.5 mg), nikethamide (1.25 g), Stedeze (4 tablets: 160 mg vitamin B, 160 mg vitamin B2, 45 mg niacin, 1 g yeast), ammonium chloride (1.0 g), or placebo according to double‐blind, within‐subjects, crossover designs. Subjects were individually tested on a battery of physiologic and behavioral measures of intoxication that included platform‐balance, divided attention and memory performance, electroencephalographic recordings, mood adjective check list, and objective and subjective inebriation ratings. In addition, blood ethanol concentrations (BECs) were monitored throughout each session. Although some antagonistic effects were found with nikethamide and ammonium chloride, none of the agents consistently reduced the degree of ethanol intoxication on the measures employed. In no instance did treatment with Stedeze significantly reduce intoxication when compared to placebo treatment (t test paired data or Wilcoxon signed‐ranks matched‐pairs test). These results indicate that none of the tested drugs represent effective sobering agents at the doses employed.
Corneal Arcus as a Sign of Possible Alcoholism
Authors: Ewing John A. , Rouse Beatrice A.
Published: February 2008

North Carolina males with alcoholism showed significantly greater age‐adjusted prevalence rates of corneal arcus than those without alcoholism. Thus, arcus senilis should always indicate to the physician the need to explore the possibility of alcoholism, particularly when it is detected in males under the age of 60.
Alcohol and Benzodiazepines: Withdrawal Syndromes
Authors: Benzer David , Cushman Paul
Published: February 2008

A mixed alcohol‐benzodiazepine (BD) addiction was recognized in 25 alcoholics who were admitted for detoxification. They experienced a withdrawal syndrome, atypical for alcoholics, starting 2–10 days after abrupt discontinuation of drugs and characterized by more psychomotor and less autonomic nervous system signs than is usual in alcohol withdrawal. The timing and nature of the specific symptoms in the mixed sedative addiction resembled BD withdrawal. Treatment with tapering oral barbiturates after sedative tolerance tests was effective. Awareness of the mixed alcohol‐BD addiction should result in improved recognition and treatment.
Acute Effects of Ethanol on Liver Blood Circulation in the Anesthetized Dog
Authors: Bravo I. R. , Acevedo C. G. , Gallardo V.
Published: February 2008

A single, intraportal injection of ethanol (0.01 g/kg body weight) in the pentobarbital anesthetized dog elicited an immediate rise in the hepatic resistance to both portal and hepatic blood flows. Similar effects were produced by norepinephrine and these, as well as those of ethanol, were significantly reduced by yohimbine. Increased levels of noradrenaline were found in hepatic venous effluent during the vasoconstriction period induced by ehtanol. We postulate that noradrenaline liberated from sympathetic nervous endings of the liver may be involved in vascular response to ethanol.
Mechanisms of Host Defense in Well Nourished Patients With Chronic Alcoholism
Authors: Ericsson Charles D. , Kohl Steve , Pickering Larry K. , Davis Jan , Glass George S. , Faillace Louis A.
Published: February 2008

Tests of immune function were performed on five recently abstinent, well nourished, and disease‐free patients with chronic alcoholism. No significant defects in adherence, metabolic, or bactericidal activity of polymorphonuclear leukocytes were found when compared to sex‐matched controls. Antibody‐dependent and natural killer cellular cytotoxicity of monocyte‐macrophages and lymphocytes also were normal. These data support the concept that immunity might be intact in the group of patients with chronic alcoholism who are recently sober, well nourished, and free of underlying disease.
Prolonged Ethanol Consumption Produces Persistent Alterations of Cholinergic Function in Rat Brain
Authors: Pelham R. W. , Marquis J. K. , Kugelmann K. , Munsat T. L.
Published: February 2008

Prolonged ethanol consumption produces neuropathology and neurologic symptoms in humans and experimental animals. As a means of understanding the central nervous system (CNS) consequences of ethanol abuse, we sought whether cholinergic neurochemical functions were altered by long‐term ethanol consumption by rats. Eighteen weeks of ethanol consumption in a liquid diet reduced rat striatal and mammillary body choline acetylase (ChAT) by 53% and 58%, respectively. In these same regions, the density of muscarinic cholinergic receptors was elevated 117% and 12%. No such alterations were observed in cortex or in hippocampus. No alterations followed short‐term ethanol consumption (2 wk), but they persisted after ethanol withdrawal (4 wk). After 13 mo of ethanol consumption, the number of neuroleptic binding sites in striatum was diminished by 29%. These results demonstrate a persistent, possibly permanent, alteration in brain cholinergic function as a consequence of long‐term ethanol ingestion. Since brain acetylcholine is involved in numerous neurologic functions, including memory processes, these findings may be relevant to the lasting memory disorder and other permanent effects associated with chronic alcoholism.
Learning and Memory Impairments in Young and Old Alcoholics: Evidence for the Premature‐Aging Hypothesis
Authors: Ryan Christopher , Butters Nelson
Published: February 2008

A battery of cognitive tests was administered to groups of younger (34–49) and older (50–59) alcoholics and nonalcoholic control subjects. Regardless of age, alcoholics were found to be impaired on essentially all measures of learning and memory. The relevance of these findings to the premature‐aging hypothesis is discussed.
Receptor‐Mediated Dopaminergic Function After Ethanol Withdrawal
Authors: Black Richard F. , Hoffman Paula L. , Tabakoff Boris
Published: February 2008

Striatal dopamine (DA) synthesis, measured in vivo as accumulation of DOPA after aromatic amino acid decarboxylase inhibition, is increased by neuroleptics and decreased by DA agonists as a result of their interactions with regulatory receptors. A sensitive high performance liquid chromatography (HPLC) technique has been developed, which allows the evaluation of both increases and decreases in DOPA levels in response to agonists and antagonists, and simultaneously permits measurement of DA levels as an indication of DA neuronal activity. C57BL mice, after chronic ethanol treatment and withdrawal, demonstrate significantly decreased responses, in terms of DOPA accumulation and DA release, to both haloperidol, a DA antagonist, and apomorphine, a DA agonist. These effects cannot be interpreted as resulting either from DA receptor subsensitivity or supersensitivity, but suggest instead that coupling between DA receptors and tyrosine hydroxylase is perturbed by ethanol treatment.
Effects of Alcohol on Psychomotor Performance of Women: Interaction With Menstrual Cycle
Authors: Linnoila M. , Erwin C. W. , Ramm D. , Cleveland W. P. , Brendle A.
Published: February 2008

The effects of alcohol on performance were investigated in 10 ovulating young women. Placebo drink and three doses of alcohol were administered in a random order both during follicular and luteal phases of the menstrual cycle. The women had significantly slower verbal information processing rate and poorer visual detection performance during the follicular than the luteal phase of the menstrual cycle. In psychomotor tasks other than tracking. dose‐response relationships of alcohol were different during the different phases of the menstrual cycle.
Chronic Alcohol Abuse and High Density Lipoprotein Cholesterol
Authors: Barboriak Joseph J. , Jacobson George R. , Cushman Paul , Herrington Roland E. , Lipo Robert F. , Daley Mark E. , Anderson Alfred J.
Published: February 2008

The possible use of high density lipoprotein cholesterol (HDLC) as a marker of alcohol abuse was studied in 92 alcoholic patients entering an inpatient treatment program. The average HDLC levels of 68 male patients (66 ± 23 mg/dl) and 24 female patients (83 ± 18 mg/dl) were significantly higher than the values for the corresponding control groups of similar ages. Approximately 20% of the male patients had HDLC levels over the mean ± 2 SD over the control groups. Following 2 wk of alcohol abstinence. the HDLC levels decreased to the control range. HDLC, as a measure of alcohol abuse, may be especially useful in combination with determination of gamma glutamyl transpeptidase (GGT), since these two tests singly or in combination were elevated in 65% of the male and 85% of the female patients.
Antagonism of Ethanol Narcosis in Mice by Hyperbaric Pressures of 4–8 Atmospheres
Authors: Alkana Ronald L. , Malcolm Richard D.
Published: February 2008

Hyperbaric treatment with 100% oxygen or oxygen‐helium mixtures at 4–8 atmospheres absolute significantly reduced ethanol sleep‐time and increased wake‐up blood ethanol concentrations in C57 mice. The results indicate that the antagonsim does not result from direct effects of oxygen nor from enhanced ethanol elimination, but appears to involve a direct effect of hyper‐baric treatment.
Individual Differences in Blood and Breath Acetaldehyde Levels and Urinary Excretion of Catecholamines After Alcohol Intake
Authors: Mizoi Yasuhiko , Hishida Shigeru , Ijiri Iwao , Maruyama Jun , Asakura Satoshi , Kijima Tetsuka , Okada Takako , Adachi Junko
Published: February 2008

Sixty three male Japanese, aged 20–40 yr were evaluated as to the degree of facial flushing following a controlled dose of ethanol either as Japanese rice wine or ethanol 0.4 g kg body weight. Thirty four subjects responded with overt facial flushing. The acetaldehyde levels in blood and expired air were significantly higher in the flushing group without a change in ethanol elimination rate. Urinary excretion of Vanilmandelic acid (VMA) and 3 methyoxy‐4‐Hydroxyphenylgiycol (MHPG) are reported.
Ethanol Oxidation by Rat Brain in Vivo
Authors: Cohen Gerald , Sinet Pierre M. , Heikkila Richard
Published: February 2008

Can brain metabolize ethanol? We present data demonstrating that brain catalase in conjunction with endogenous H2O2 will oxidize ethanol in vivo. The method is based on an H2O2‐dependent inhibition of brain catalase in vivo by 3‐amino‐1,2.4‐triazole and its prevention by ethanol. The irreversible inhibition of catalase by aminotriazole is known to proceed via the reaction of (catalase‐H2O2) compound I with aminotriazole. Inhibition can be prevented by compounds that are oxidized by compound I. Ethanol is one such compound. Prevention of the inhibition of brain catalase in vivo by prior administration of ethanol constitutes indirect evidence for the oxidation of ethanol to acetalde‐hyde in rat brain. The catalase content of the tissues represented catalase in the brain parenchyma, from which erythrocytes and capillaries had been excluded. Ethanol did not alter the levels of aminotriazole in brain. These results constitute the first demonstration of ethanol oxidation by living brain.
Correlation Between Medical and Behavioral Data in the Assessment of Alcoholism
Authors: Skinner Harvey A. , Holt Stephen , Allen Barbara A. , Haakonson Lt. Col. N. Harvey
Published: February 2008

Using the Munich Alcoholism Test, this study examined the prevalence and interrelationships of medical and sociobehavioral disorders in a nonhospitalized sample of 106 males who had been referred to a medical officer for “suspected” problems related to drinking. A further objective was to evaluate measurement properties of the Munich Alcoholism Test (MALT), a new diagnostic instrument for alcoholism. Self‐report items focusing on the recognition of drinking problems formed a homogeneous and quite reliable scale. However, clinical signs and symptoms of disorders related to alcohol abuse occurred with relative independence of each other. In this predominantly young group of subjects, many individuals recognized that they had sociobehavioral problems, but few had clinical or laboratory manifestations of diseases associated with chronic alcohol abuse. These findings underscored the advantages of including both biomedical and sociobehavioral data for the early identification of alcohol abuse and dependence.
Methanol Toxicity: Treatment With Folic Acid and 5‐Formyl Tetrahydrofolic Acid
Authors: Noker P. E. , Eells J. T. , Tephly T. R.
Published: February 2008

After methanol administration to monkeys, an accumulation of formate in blood occurs coincident with the development of metabolic acidosis and a depletion of blood bicarbonate. Formate metabolism in monkeys depends upon and is regulated by a folate‐dependent system; therefore, the effect of folic acid pretreatment and 5‐formyl tetrahydrofolic acid administration on methanol toxicity was investigated. Treatment of monkeys with repetitive doses of either sodium folate (48, 24, 12, and 4 hr prior to methanol) or 5‐formyl tetrahydrofolic acid (2 mg/kg at 0, 4, 8, 12, and 18 hr after methanol) resulted in a marked decrease in the levels of blood formate and an absence of both metabolic acidosis and depletion of blood bicarbonate following methanol administration. Also, 5‐formyl tetrahydrofolic acid reversed methanol toxicity once it was established in the monkey. The results indicate that folate compounds decrease formate accumulation after methanol by stimulating formate oxidation or utilization and suggest a possible use for folates in the treatment of certain cases of human methanol poisoning.
Nonlinear Pharmacokinetics Of Ethanol: The Disproportionate AUC‐Dose Relationship
Authors: Wilkinson P. K. , Reynolds G. , Yang S. , Wilkin L. O.
Published: February 2008

Whole venous blood concentrations of ethyl alcohol were measured following the constant rate intravenous infusion of ethanol to four Beagle dogs. Five different doses (0.1–0.8 g ethanol/kg body weight) were administered at scheduled intervals. The area under the blood ethanol concentration‐time curves (AUC) was found to demonstrate a markedly nonlinear relationship with the administered dose. Simulations of one and two compartment open models with Michaelis‐Menten elimination kinetics and zero‐order input are presented with their theoretical AUC‐dose relationships.
Disulfiram Distribution and Elimination in the Rat After Oral and Intraperitoneal Administration
Authors: Faiman Morris D. , Artman Linda , Haya Katsuji
Published: February 2008

35S disulfiram (DSF), 7 mg/kg, was administered as a single dose to rats both orally (p.o.) or intraperitoneally (i.p.). The 35S DSF was rapidly absorbed by either route. Kidney, pancreas, liver, and the gastrointestinal tract exhibited the greatest uptake of radioactivity, while the least was found in brain. Preferential tissue uptake was similar with both routes of administration. Seven percent of the dose was excreted in the feces. Approximately 12% of the dose was eliminated by the breath as CS2. The 35S‐DSF was rapidly metabolized to the 35S‐diethyldi‐thiocarbamate‐glucuronide and 3BS inorganic sulfate. Approximately 93% of the radioactivity was accounted for 48 hr after p.o. or i.p. 35S administration.
Biochemical Evidence for an Interaction of Ethanol and Stress: Preliminary Studies
Authors: Pohorecky L. A. , Rassi E. , Weiss J. M. , Michalak V.
Published: February 2008

Studies were carried out to examine the interaction of stress and ethanol. Ethanol (0.5 g/kg)‐treated, stressed (electric foot shocks) rats exhibited less marked elevations in plasma levels of nonesterified fatty acids and of corticosterone compared to saline‐treated stressed subjects. Stress alone markedly elevated these two parameters in plasma. Ethanol treatment alone also resulted in small elevations in both parameters. Results provide support for a significant interaction of ethanol and stress, and might provide some basis for the purported stress‐relieving effect of low doses of ethanol.
Fetal Alcohol Syndrome in Sinclair(S‐l) Miniature Swine
Authors: Dexter James D. , Tumbleson Myron E. , Decker John D. , Middleton Charles C.
Published: February 2008

Piglets from 12 litters farrowed by 18‐mo‐old, first litter (L1) alcohol‐consuming dams were evaluated for altered morphology. A second group of piglets, farrowed by six 3‐yr‐old, second litter (L2) alcohol‐consuming dams, was also evaluated. Litters from 6 non‐alcohol‐consuming gilts and 6 non‐alcohol‐consuming sows were used as controls. Mean litter size and birth weight for L, and L2 piglets were significantly less than controls. Fetal mortality rates for L, and L2 piglets were much greater than controls. Anomaly rates observed in fetal deaths were 11% and 100% for L1 and L2, respectively; no anomalies were seen in the control group piglets. Anomalies observed in group L1 included prolapsed rectum, undescended testicle, hypoplastic testicular tissue, and microphthalmia. Anomalies seen in group L2 included one occurrence of each of the following: anencephaly, microcephaly, cranial bone hypoplasia, microphthalmia, cleft palate, hypoplasia of extremities, hypodactylia, poly‐dactylia, cryptorchism, hypoplastic gonadal tissue, cloacal atresia, and two occurrences of micrognathia, syndactylia, and hypoplasia of tail. Open‐field activity behavioral studies show significantly greater activity in the offspring of alcohol‐consuming dams. The data from Sin‐clair(S‐l) miniature swine support the data from other species, establishing the relationship between maternal alcohol consumption and fetal anomalies.
Effect of Ethanol and Ethanol‐Induced Hypothermia on Protein Synthesis in Pregnant and Fetal Rats
Authors: Henderson George I. , Hoyumpa Anastacio M. , Rothschild Marcus A. , Schenker Steven
Published: February 2008

The effects of acute and chronic maternal ethanol intake and concomitant hypothermia on in vivo net protein synthesis in maternal and fetal tissues were investigated. No consistent effect on net protein synthesis was found in rats chronically exposed to ethanol if they were tested at a time when blood alcohol levels averaged 0.76 mg/ml and body temperatures were normal (38°C). If rats chronically exposed to ethanol were given ethanol acutely, which raised blood ethanol levels to 3 mg/ml and reduced maternal body temperature by 2.3°C, net protein synthesis was significantly (p < 0.05) reduced in maternal brain and viscera, placenta, and in fetal brain and viscera. Acute ethanol exposure alone, yielding blood levels of 2.7 mg/ml and reducing maternal body temperature by over 2°C, also significantly (p < 0.05) reduced net protein synthesis in the same tissues. In both groups of animals hypothermia was then eliminated to assess the effects of ethanol alone on protein synthesis. The etha‐nol‐induced hypothermia was found to be the major contributor to the observed depression in net protein synthesis in maternal brain and heart and in fetal brain. However, at high blood ethanol levels, ethanol directly, independent of hypothermia, also reduced net protein synthesis in maternal kidney, liver, and placenta, and in fetal heart, kidney, and liver. In conclusion, both ethanol‐induced hypothermia (to a major degree) and ethanol per se, at blood ethanol levels in excess of 1 mg/ml, depress net protein synthesis in vivo in rats.
Altered Immunity in Male Patients with Alcoholic Liver Disease: Evidence for Defective Immune Regulation
Authors: Smith William I. , Thiel David H. Van , Whiteside Teresa , Janoson Bernard , Magovern James , Puet Terry , Rabin Bruce S.
Published: February 2008

We sought evidence for altered immunity in patients with alcoholic liver disease, and we correlated the observed immunologic abnormalities with the extent of histologically proven liver disease. Total circulating lymphocytes and the absolute number of T lymphocytes were decreased in alcoholics (p < 0.01) compared to controls. Immunoglobulins G and A were elevated significantly (p < 0.05) in alcoholic patients with hepatic fibrosis or cirrhosis compared to controls and alcoholics without such liver histopathology. In alcoholics with fibrosis or cirrhosis at time of admission, IgE levels were also elevated (p < 0.01) but decreased 50% during hospitalization. Forty‐eight percent of the patients with alcoholic liver disease had antibodies to small bowel epithelium, and 33% had antibodies to fibroblast cytoplasm. In addition, we found that alcoholics immunized with polyvalent pneumococcal polysaccharide responded with significantly elevated (p < 0.025) antibody titers compared to hospitalized controls. In aggregate, these findings in patients with alcoholic liver disease are consistent with a defect in immune regulation.
Effect of Ethanol Feeding upon Levels of a Male‐Specific Hepatic Estrogen‐Binding Protein: A Possible Mechanism for Feminization
Authors: Eagon Patricia K. , Porter Lynne E. , Gavaler Judith S. , Egler Kimberly M. , Thiel David H. Van
Published: February 2008

Male, but not female, rat liver cytosol contains an estrogen‐binding protein with unique properties: rapid binding of estradiol, high binding capacity, moderate affinity for estradiol, and specificity for steroidal estrogens and weak androgens, but not for nonsteroidal estrogens or other steroids. The estradiol‐binding activity of this protein is reduced in cytosol from livers of alcohol‐fed rats as compared to that from their isoca‐lorically fed controls. The properties of this male‐specific hepatic estrogen‐binding protein suggest a role for this protein in the regulation of estrogen levels in the male animal. Moreover, the reduction in activity of this unique protein in the liver of alcohol‐fed animals may explain, at least in part, the feminization commonly seen in chronic alcoholic men.
HLA Antigen Frequencies in Cirrhotic and Noncirrhotic Male Alcoholics: A Controlled Study
Authors: Rada Richard T. , Knodell Robert G. , Troup Gary M. , Keilner Robert , Hermanson Susan M. , Richards Meri
Published: February 2008

Although epidemiological data suggest that the development of cirrhosis in alcohol abusers is related to the duration and amount of ethanol intake, the fact that only a small percentage of alcohol abusers develop cirrhosis remains unexplained and suggests a possible predisposing genetic factor. Several previous studies have reported an association between various human leucocyte antigens (HLA) and alcoholic cirrhosis. In this study HLA antigen frequencies were determined in Anglo‐ and Spanish‐American cirrhotic and noncirrhotic alcoholics and in a control group of nonalcoholic patients without liver disease. No statistically significant differences in HLA frequencies among the groups were found. Our comparisons of HLA frequencies between cirrhotic and noncirrhotic alcoholic patients do not support the hypothesis that individual susceptibility to the development of alcoholic cirrhosis is genetically determined.
Effect of Chronic Ethanol Administration on Plasma Levels of LH and the Estrous Cycle in the Female Rat
Authors: Eskay Robert L. , Ryback Ralph S. , Goldman Mark , Majchrowicz E.
Published: February 2008

Intragastric intubation of 4 or 8 g/kg of body weight of ethanol per day for 12 consecutive days disrupted the normal estrous cycle in female rats as monitored by vaginal epithelial cell changes. Plasma luteinizing hormone levels were unchanged suggesting that blood ethanol in the 50–100 mg/100 ml range acted as a direct gonadal toxin and not at the hypothalamic‐pitui‐tary gland level.
Sterol Metabolism in the Rat: Effect of Alcohol on Sterol Metabolism in Two Strains of Rats
Authors: Cohen Bertram I. , Raicht Robert F.
Published: February 2008

Sterol metabolism studies usinag a combination of iso‐topic and chromatographic procedures were carried out in two strains of rats fed 5% ethanol (36% of calories) in the diet.

Feeding ethanol to the Fisher rat over 17 days produced no significant changes in body weight. Cholesterol levels in various tissues were elevated in the ethanol‐fed group: plasma cholesterol, +61%; liver cholesterol, +47%; and bile cholesterol, +57%. The alcohol‐fed Fisher rat showed several changes in sterol metabolism over controls: fecal acidic steroid output, + 13%; fecal neutral sterol output, +51%; endogenous neutral sterol output, +107%; cholesterol turnover, + 54%; and cholesterol balance, +18%.

Ethanol feeding to the Spraque Dawley rat showed similar differences between ethanol‐fed vs. control rats. Cholesterol levels were significantly elevated in plasma (+35%) and in the liver (+81%). Sterol metabolism data showed the following differences (alcohol vs. control): fecal acidic steroid output, +9%; fecal neutral sterol output, +17%; endogenous neutral sterol output, +72%; cholesterol turnover, +33%; and cholesterol balance, +13%.

The Fisher rat maintained almost constant weight throughout the experimental period and is a preferable strain for sterol balance studies using liquid diets. A major finding of these experiments was the increased concentration of cholesterol in liver, plasma, and bile in both strains of rats. The sterol balance measurements indicated that this tissue accumulation of cholesterol was due to enhanced cholesterol synthesis as well as inhibition of bile acid synthesis.
An Evaluation of the Effects of Lithium in the Treatment of Chronic Alcoholism, Clinical Results
Authors: Pond Susan M. , Becker Charles E. , Vandervoort Ruth , Phillips Michael , Bowler Rose Marie , Peck Carl C.
Published: February 2008

To evaluate the efficacy of lithium in chronic alcoholism, we enrolled 47 male alcoholics in a prospective double‐blind two‐period crossover study. Nineteen subjects completed the 6‐mo study during which they received lithium and placebo each for a 3‐mo period. Self‐reported alcohol intake and social and psychological factors were monitored. Three subjects claimed that they did not drink during the study. Mean self‐reported alcohol intake of the remaining 16 was less during lithium therapy but was also less during the first treatment period. Neither of these differences reached statistical significance. The nine depressed patients, diagnosed from their profiles on the Minnesota Multiphasic Personality Inventory did not consume significantly less alcohol and did not change scores for depression significantly during lithium therapy. We could not demonstrate that lithium therapy was of benefit in our group of alcoholic patients.
Plasma α‐Amino‐n‐Butyric Acid/Leucine Ratio in Alcoholics
Authors: Jones James D. , Morse Robert M. , Hurt Richard D.
Published: February 2008

Fasting free amino acid concentrations in plasma of 20 control and 18 alcoholic subjects were compared in an attempt to validate previous reports that the molar ratio of α‐amino‐n‐butyric acid/leucine (A/L ratio) is a marker for alcoholism. We were unable to confirm the observations of either altered α‐amino‐n‐butyric acid or leucine concentrations or an increased A/L ratio in alcoholic subjects, and we conclude that the A/L ratio is not a biochemical marker for alcoholism.
Medical Status and Cognitive Functioning in Alcoholic Women
Authors: Jones‐Saumty Deborah J. , Fabian Marjorie S. , Parsons Oscar A.
Published: February 2008

The prevalence of physical health disorders and measures of cognitive functioning were compared for 100 alcoholic and 100 nonalcoholic women matched on age and education. Alcoholic women were less healthy and more impaired on visual‐spatial tasks than nonalcoholic women, and there were no relationships between health and cognitive functioning for either group.
Differential Effects of TRH, Amphetamine, Naloxone, and Fenmetozole on Ethanol Actions: Attenuation of the Effects of Punishment and Impairment of Aerial Righting Reflex
Authors: Vogel R. A. , Frye G. D. , Koepke K. Mann , Mailman R. B. , Mueller R. A. , Breese G. R.
Published: February 2008

The effects of four putative ethanol antagonists [thyrotropin releasing hormone (TRH), naloxone, d‐amphetamine, and fenmetozole] on two distinct behavioral actions of ethanol were compared. TRH (20–40 mg/kg) reduced ethanol‐induced impairment of the aerial righting reflex (ARR) but enhanced the ethanol‐induced increase in punished drinking (anticonflict effect). Naloxone antagonized both actions of ethanol but only at high doses (20–60 mg/kg). Amphetamine (1–4 mg/kg) abolished the ethanol effect on punished drinking but did not alter its impairment of the ARR (1 ‐8 mg/kg). Conversely, fenmetozole antagonized the ethanol impairment of the ARR (15–30 mg/kg) but not ethanol's anticonflict action. The inconsistent pattern of “antagonist” interactions of these drugs with the behavioral actions of ethanol suggests that ethanol alters several neurochemical systems to produce its behavioral effects.
Effect of Dietary Ethanol and Cholesterol on Metabolic Functions of Hepatic Mitochondria and Microsomes from the Monkey, Macaca nemestrina
Authors: Cunningham Carol C. , Sinthusek Govit , Spach Priscilla I. , Leathers Charles
Published: February 2008

Monkeys (Macaca nemestrina) were divided into four groups, and each group was fed a particular diet. The variables in the diets were as follows: diet A, 0.3 mg cholesterol/kcal nutrient; diet B, 1.0 mg cholesterol/kcal nutrient; diet C, 0.3 mg cholesterol/kcal nutrient, ethanol (36% of calories); diet D, i.O mg cholesterol/ kcal nutrient, ethanol (36% of calories). Monkeys on the diets containing ethanol developed fatty liver. Mitochondria from ethanol‐fed animals demonstrated significant decreases in uncoupler‐stimulated, state 3, and state 4 succinate oxidation activity; respiratory control ratio; and ATP content. Liver microsomes isolated from the ethanol‐fed groups demonstrated increased ethanol oxidizing activity with either NADPH or H2O2 as cosubstrate. Aniline hydroxylase and ami‐nopyrine‐N‐demethylase activities were also elevated in ethanol‐fed animals. The alterations in these functional properties were related primarily to ethanol in the diets. Cholesterol, while being less of a perturbant than ethanol, did elicit a significant decrease in cytochrome oxidase activity of mitochondria and a small but statistically significant increase in microsomal‐associated ethanol oxidation activity. It appeared to potentiate the effect of ethanol in lowering mitochondrial respiratory control and ATP concentrations.
Effect of Dietary Ethanol and Cholesterol on Phospholipid Composition of Hepatic Mitochondria and Microsomes from the Monkey, Macaca nemestrina
Authors: Cunningham Carol C. , Sinthusek Govit , Spach Priscilla I. , Leathers Charles
Published: February 2008

Monkeys (Macaca nemestrina) were divided into four groups, and each group was fed a particular diet. The variables in the diets were as follows: diet A, 0.3 mg cholesterol/kcal nutrient; diet B, 1.0 mg cholesterol/kcal nutrient; diet C, 0.3 mg cholesterol/kcal nutrient, ethanol (36% of calories); diet D, 1.0 mg cholesterol/ kcal nutrient, ethanol (36% of calories). Monkeys on the diets containing ethanol developed fatty liver. Mitochondria and microsomes isolated from these livers demonstrated ethanol‐elicited alterations in metabolic functions as is described in the preceding paper.1 Accompanying these changes in metabolic activities were alterations in organelle phospholipids that were influenced by both dietary ethanol and cholesterol. The changes that could be attributed to ethanol were as follows. Phosphatidyl ethanolamine was decreased in microsomes and increased in mitochondria; the sphingomyelin content in microsomes was increased significantly. The levels of stearic and arachidonic acid were elevated, and palmitic and oleic acid decreased, in phospholipids from both mitochondria and microsomes. Cholesterol influenced the fatty acid composition of several phospholipids, usually in a direction opposite to those alterations attributed to ethanol. Cholesterol feeding increased levels of palmitic and oleic acid and decreased amounts of stearic, linoleic, and arachidonic acid in several phospholipids. The significant ethanol‐ and cholesterol‐elicited alterations observed in this study suggest the possibility that the changes in metabolic functions in mitochondria and microsomes are controlled, at least in part, by alterations in the phospholipid compositions of these organmicrosomes are controlled, at least In part, by alterations in the phospholipid compositions of these organelles.
Outcome of Alcoholism Treatment Among 5578 Patients in an Urban Comprehensive Hospital‐Based Program: Application of a Computerized Data System
Authors: Gordis Enoch , Dorph Douglas , Sepe Vincent , Smith Harry
Published: February 2008

The Elmhurst Alcoholism Program data system relate* fraction of time patients are in remission to length of time they are known, and permits a systematic search for groups of variables which predict greater abstinence rates. Our program (inpatient detoxification ward, multidisciplinary outpatient clinic, and halfway house) sets abstinence as a goal. After initial data collection (social and demographic variables, income, education, residence, drinking and drug history, legal problems, and prior treatment), we collect data at 30 days after admission and at 2‐ or 3‐month intervals thereafter from all patients who remain in contact. Forty‐five percent of all patients are lost before 30 days. Only 32% of those still under observation at 1 yr and 27% of those still under observation at 2 yr claim continual abstinence. From among many combinations of variables examined for predictive power, a group of five was chosen as best. Patients who at their first follow‐up interview reported attending AA meetings and taking Antabuse and who in addition had a job at admission, were older, and were admitted through the clinic rather than through inpatient detoxification had a greater fraction of time abstinent. Nevertheless, the best cluster of predictor variables did not account for more than 25% of the variation in rates of abstinence. Many social variables are not independent, and some may merely be indicators of duration or severity of alcoholism. Contemporary alcoholism treatment is, at best, of limited effectiveness.
The Disulfiram (Antabuse)‐Alcohol Reaction in Male Alcoholics: Its Efficient Management by 4‐Methylpyrazole
Authors: Lindros Kai O. , Stowell Allan , Pikkarainen Pekka , Salaspuro Mikko
Published: February 2008

4‐Methylpyrazole (4‐MP), an inhibitor of alcchol dehydrogenase, rapidly abolished the accumulation of acetaldehyde following alcohol ingestion both in volunteers pretreated with the Antabuse analog calcium carbimide and in an Antabuse‐treated alcoholic. 4‐MP also attenuated other typical symptoms, including facial flushing and tachycardia, thus suggesting its usefulness in the acute treatment of severe disulfiram‐alcohol reactions.
Ethanol‐Induced Changes in Cardiac Lipid Metabolism
Authors: Somer John B. , Colley Peter W. , Pirola Romano C. , Wilson Jeremy S.
Published: February 2008

The influence of ethanol on cardiac lipid metabolism has been investigated in the rat. Acute in vitro ethanol significantly stimulated the incorporation of 14C‐1‐acetate but not 14C‐U‐glucose into cardiac lipid in rats fed a diet free of ethanol for 3 weeks. Stimulation of incorporation was not uniform but was confined to the diglyceride and triglyceride fractions. This response of cardiac tissue lipid metabolism to acute ethanol was not observed in rats pair fed an isocaloric diet containing 36% of calories as ethanol. Chronic ethanol feeding significantly increased cardiac triglyceride content when compared with pair‐fed controls. It also stimulated oxidation of labeled palmitate, but did not affect in vitro lipogenesis.
Gamma‐Glutamyl Transpeptidase and High‐Density Lipoproteins Cholesterol in Male Problem Drinkers: Advantages of a Composite Index for Predicting Alcohol Consumption
Authors: Sanchez‐Craig Martha , Annis Helen M.
Published: February 2008

Forty mate problem drinkers, participants of a treatment follow‐up study, were assessed for levels of y‐glutamyl transpeptidase (GGTP) and high‐density lipoproteins cholesterol (HDL‐C) in relationship to self‐reported alcohol consumption over the previous 3‐week period. A composite index of GGTP and HDL‐C was superior to GGTP or HDL‐C alone in discriminating abstinent/light, moderate, and heavy drinkers.
Ether Inhibition of Ethanol Metabolism in Isolated Rat Liver Parenchymal Cells
Authors: Aune Hakon , Stowell Allan R. , Morland Jorg
Published: February 2008

The effect of diethyl ether on ethanol metabolism was studied in isolated rat hepatocytes and ether was found to inhibit ethanol oxidation in a dose‐dependent manner. At ethanol concentrations of approximately 30 DIM, diethyl ether inhibited ethanol oxidation by approximately 58%, 40%, and 20% at ether concentrations of 30,20, and 10 mm, respectively. This inhibition was also seen at a low ethanol concentration (5.4 MM) and in pyruvate (5 mM)‐stimulated hepatocytes which exhibited increased rates of ethanol metabolism closer to in vivo rates. Accumulation of acetaldehyde from ethanol in cyanamide (400 μM)‐treated hepatocyte suspensions was also reduced by approximately 16% by 30 HIM ether, ft was concluded that inhibition of ethanol metabolism by diethyl ether might be of practical importance in studies of ethanol metabolism in ether anesthetized animals.
Altered Invertebrate Nerve Function after Chronic Exposure to Low Concentrations of Alcohol
Authors: Borowsky Stephen A. , Junge Douglas
Published: February 2008

Previous studies of direct alcohol toxicity on nerve tissue have been carried out using acute, extremely high doses of alcohol. Chronic administration of 20 mM ethanol to the mollusc Aplysia californica was achieved by adding ethanol to surrounding seawater. Although the animals appeared healthy, isolated ganglion cells from treated animals had significantly decreased mean action potential amplitudes and prolonged mean action potential durations compared to controls. These findings suggest that chronic exposure to a low concentration of ethanol comparable to that producing drunke‐ness in humans may have a direct toxic effect on invertebrate nerve tissue.
Sex‐Related Differences in Ethanol‐Induced Liver Disease: Artifactual or Real?
Authors: Gavaler Judith S.
Published: February 2008

The cross‐sectional, observational studies from four groups which have reported a difference between males and females in susceptibility to ethanol‐induced liver disease are reviewed. Crucial factors of representativeness of sampled groups, certainty of cirrhosis diagnosis, and quantitation of ethanol intake are examined. Attention is given to the direction of differences between males and females in the variables suggestive of differential susceptibility: age at presentation, years of excessive drinking, age at which excessive drinking began, percent of alcoholics of each sex diagnosed as having cirrhosis, age at death due to cirrhosis, daily ethanol intake, and the male to female ratio among cirrhotics as compared to alcoholics. Based on the consistency of findings among the studies reviewed, as demonstrated by replication of results obtained under different conditions of time, place, methodology, and subsamples of alcoholics studied, a conclusion of enhanced susceptibility to ethanol‐induced liver disease among women is reached. Finally, factors which may lend biological plausibility to the above susceptibility differential are considered.