bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug Therapy in the Elderly: The Clinical Pharmacology of Aging
Authors: Lee Peter V.
Published: February 2008

It is becoming increasingly apparent that age and the changes of aging are factors to be taken into account in drug therapy and in the study of drug actions. Older people have more adverse reactions to drugs than do younger people. Several studies in hospitalized patients have confirmed the fact that the incidence of untoward reactions to drugs increases with advancing age.
Alcoholism and Aviation Medical Certification
Authors: Pakull Barton
Published: February 2008

A “history” of alcoholism may be 2 mo old or 20 yr ago. No two individuals are completely alike, and it would be nearly impossible to write a satisfactory regulation that could define when an individual is medically safe to return to flying. Individual consideration would seem to be the fairest way to deal with this issue.
Alcohol Metabolism and Sensitivity Reactions Among the Reddis of South India
Authors: Schaefer James M.
Published: February 2008

Alcohol was given orally to 41 healthy young male volunteers from small Hindu (Reddis) farming villages in south and central Andhra Pradesh, India. A complete description of the Reddis study, plus transcultural group differences, is given, and the alcohol metabolism and sensitivity literature is critically reviewed.
Racial Differences in Circadian Variation of Ethanol Metabolism
Authors: Zeiner Arthur R. , Paredes Alfonso
Published: February 2008

In two experiments, independent groups of male social drinkers were administered equal doses of ethanol per unit of body weight (0.66 ml/kg) at different times during the day. Peak blood alcohol concentration (BAC) was achieved, and the time taken to return to a BAC of 20 mg/100 ml and the rate of ethanol metabolism per hour were determined.
Psychiatric Disturbances in Drunk Driving Offenders Referred for Treatment of Alcoholism
Authors: Mulligan Michael J. , Steer Robert A. , Fine Eric W.
Published: February 2008

The incidence of psychopathology in persons arrested for driving while intoxicated (DWI) has serious implications in both alcoholism treatment and in general highway safety. This study investigated the types of psychopathology, as measured by the Minnesota Multiphasic Personality Inventory (MMPI), in a sample of 116 males referred for treatment by a court diversion program.
Putative Role of Isoquinoline Alkaloids in Alcoholism: A Link to Opiates
Authors: Blum Kenneth , Hamilton Murray G. , Hirst Maurice , Wallace Jack E.
Published: February 2008

The purpose of this article is to review the present level of knowledge and provide new data with regard to delineating the possible role of isoquinoline alkaloids in ethanol's acute and chronic actions and how these alkaloids may serve as biochemical mediators to the highly addictive opiate(s).
The Synaptic Properties of Some Tetrahydroisoquinoline Alkaloids
Authors: Cohen Gerald
Published: February 2008

The ability of TIQs to alter the synaptic properties of catecholamines by interacting with receptor, transport, or metabolic mechanisms has been demonstrated.
Relationship between 3,4‐Dihydroxyphenylacetaldehyde Levels and Tetrahydropapaveroline Formation
Authors: Weiner Henry
Published: February 2008

It was demonstrated that DOPAL, the aldehyde derived from the action of MAO on dopamine, can condense with dopamine to form THP. This compound is of special interest, since it is an intermediate in the biosynthesis of morphine.
Inhibition of High Affinity Calcium Binding by Salsolinol
Authors: Ross David H.
Published: February 2008

Recently, the discovery of endogenous opiate peptides has reawakened new interest in the possibility that an endogenous chemical may mediate actions of alcohol and lead to ethanol dependence.
Alcohol Consumption in Pregnant Women and the Outcome of Pregnancy
Authors: Kaminski M. , Rumeau C. , Schwartz D.
Published: February 2008

This article presents the results of a study of the outcome of pregnancy and its relationship to alcohol use. The results are based on a prospective investigation of more than 9000 births.
Stability of Intelligence in the Fetal Alcohol Syndrome: A Preliminary Report
Authors: Streissguth Ann Pytkowicz , Herman Cynthia S. , Smith David W.
Published: February 2008

A clinical sample of 17 patients with fetal alcohol syndrome was given follow‐up IQ testing 1–4 yr after an initial evaluation. Although 77% of the patients had a retest IQ that was within 1 SD of their initial IQ, some individual children did manifest considerable change in scores on retest. Repeated psychologic evaluation at regular intervals is recommended for children with fetal alcohol syndrome so that appropriate educational programming can be maintained in order to promote maximum development in each child.
Alcoholic Liver Disease: The Problem of Diagnosis
Authors: Rankin J. G. D. , Orrego‐Matte H. , Deschênes J. , Medline A. , Findlay J. E. , Armstrong A. I. M.
Published: February 2008

The objective of this article is to draw attention to the serious lack of correlation that exists between the detection and specific diagnosis of liver disease in alcoholic patients, based on clinical findings and investigations other than liver biopsy and histologic diagnosis established by that technique.
The Prevention of Alcoholism: An Empirical Report on the Effects of Outlet Availability
Authors: Parker Douglas A. , Wolz Michael W. , Harford Thomas C.
Published: February 2008

Recent studies suggest that alcohol availability as measured by outlet rates is unrelated to per capita consumption or rates of alcoholism in the United States. Drawing from the same data bases, this article assesses the effects of outlet rates while controlling for the effects of per capita income, urbanism, and limitations by population on the number of sales outlets. The analysis discloses strong effects of outlet availability on per capita consumption and alcoholism rates in states that do not have restrictions on the number of outlets per unit of population.
The Navy Alcoholism Prevention Program—Worldwide
Authors: Brownell Stuart M.
Published: February 2008

Where we used to separate alcoholic members, we are now able to keep over 70% on active duty longer, which contributes to stability of the force, reductions in recruitment and training costs, and overall improved personnel readiness to support the Navy mission.
Methods for Detecting Disulfiram in Biologic Fluids: Application in Studies of Compliance and Effect of Divalent Cations on Bioavailability
Authors: Rogers Walter K. , Wilson K. Margaret , Becker Charles E.
Published: February 2008

Studies regarding the efficacy of disulfiram in the treatment of alcoholism have not included a method of evaluating compliance to the prescribed regimen. This article outlines current methods used to detect disulfiram in blood, breath, and urine.
The American Association for the Study and Cure of Inebriety
Authors: Blumberg Leonard
Published: February 2008

Beginning of the American Association for the Study and Cure of Inebriety (November 1870) and throughout its history, the leadership perceived that it was at the forefront of a therapeutic social movement—the pioneer of a new medical viewpoint as well as a new medical specialty.
An Analytic Comparison of Persons Arrested for Driving While Intoxicated and Alcohol Detoxification Patients
Authors: Ed.D. Roger A. Bell. , Warheit George J. , Bell Richard A. , Sanders Grover
Published: February 2008

This article presents findings on an analytic comparison of two groups of persons for whom alcohol is an identified clinical or social problem—247 patients currently under treatment in a detoxification unit in a general hospital and 118 individuals who had been arrested for driving while intoxicated (DWI) and were attending a DWI school. A systematic comparison of these two groups yielded several important, statistically significant differences and it becomes increasingly apparent that distinctions can be made that permit the identification of high‐risk segments of the DWI population, facilitating early diagnosis and differential treatment modes.
Effects of Alcohol on Plasma Testosterone and Luteinizing Hormone Levels
Authors: Mendelson Jack H. , Ellingboe James , Mello Nancy K. , Kuehnle John
Published: February 2008

The findings obtained in this study indicate that the major effect of ethanol on plasma testosterone levels is occurring at a peripheral (testicular) rather than central (hypothalamic‐pituitary) site.
The Effects of Alcoholic Liver Disease and Alcohol Ingestion on Sex Hormone Levels
Authors: Gordon Gary G. , Southren A. Louis , Lieber Charles S.
Published: February 2008

This study showed that alcohol significantly decreases plasma testosterone levels, with changes noted as early as the first day of alcohol use (loss of pulsatile secretion). This effect is due. in part, to a direct testicular action since it occurred without LH suppression and in the presence of elevated LH levels. More chronic use of alcohol resulted in a suppression of LH. Thus, alcohol use in nonalcoholic men is associated with an effect both at the testicular and hypothalamic‐pituitary levels.
Further Evidence for Hypothalamic‐Pituitary Dysfunction in Alcoholic Men
Authors: Thiel David H. Van , Lester Roger
Published: February 2008

Reduced plasma levels of testosterone and a high frequency of azoospermia have frequently been reported in alcoholic men. Despite the high grade of gonadal failure present, plasma gonadotropins have ranged from normal to only moderately increased. This has been interpreted as suggesting that a central hypothalamic‐pituitary defect also might exist in these men. Clomiphene stimulation studies have been consistent with the hypothesis of a central defect. The present work consists of studies utilizing luteinizing hormone‐releasing factor and thyrotropin‐releasing factor in an effort to examine the hypothesis of whether this central defect exists and, if so, whether at an anatomic, hypothalamic, or pituitary level.
Ethanol Increases Rate of Isolated Atria
Authors: Lake David A. , Chilian William M. , Roberts Lou Anne
Published: February 2008

Ethanol has a positive chronotropic and negative inotropic effect on isolated spontaneously beating rabbit atria. Both effects increased with increasing ethanol concentrations in the bathing medium. This response is apparently a direct action of ethanol on the myocardium and is not due to the release of catecholamines, acetylcholine, or acetaldehyde produced by the oxidative metabolism of ethanol. Ethanol is one of the few pharmacologic agents having opposite actions on heart rate and force of contraction.
Transient Suppression of Growth Hormone Secretion after Chronic Ethanol Intake
Authors: Ganda Om P. , Sawin Clark T. , Iber Frank , Glennon Joseph A. , Mitchell Marvin L.
Published: February 2008

Fifty‐two percent of patients with chronic heavy intake of ethanol had an abnormally low growth hormone (GH) response to propranolol‐glucagon. The effect of ethanol is transient, since the GH response was normal in patients studied 2 wk or more after withdrawal of ethanol. The low GH response was not due to a difference in the levels of glucose or insulin. Ethanol probably suppresses the GH response by acting on the hypothalamus or pituitary gland. Along with previous data suggesting transient ACTH deficiency in chronic alcoholic patients, our findings suggest that these patients may have multiple hypothalamic‐pituitary deficiencies.
Effect of an Acute Dose of Ethanol on Rat Liver Microsomal Mixed Function Oxygenase Components and Membrane Lipid Composition
Authors: Pennington Sam N. , Smith Carlton P. , Tapscott Edward B.
Published: February 2008

The lipid composition of rat liver microsomes was not altered in response to a single acute dose of ethanol relative to isocaloric glycerol‐treated controls. Microsomal cytochrome P‐450 was transiently elevated, the elevation paralleling blood ethanol levels. Microsomal NADPH oxidase was transiently elevated relative to the activity in isocaloric glycerol‐treated controls.
Changes in the Metabolism of Biogenic Amines in Alcoholism—Especially Regarding CSF Monoamine Metabolites and Serum DBH Activity
Authors: Kato Nobukatsu , Takahashi Saburo , Tani Naosuke , Iwase Norifumi , Odani Keiichi
Published: February 2008

Concentrations of the major metabolites of biogenic amines in cerebrospinal fluid and activity of serum dopamine‐β‐hydroxylase in abstinent alcoholics were measured, suggesting that withdrawal symptoms of alcoholics were based on the abnormality of serotonin and dopamine metabolism in the body.
Alterations in Phospholipid Composition in Ethanol Tolerance and Dependence
Authors: Littleton John M. , John Geryk R. , Grieve Susan J.
Published: February 2008

Mammalian cells may retain a limited capacity to alter membrane phospholipid fatty acid composition. This may play a role in adaptation to the presence of ethanol (cellular tolerance) and in the response to the removal of ethanol and the withdrawal syndrome.
Alcoholic Liver Damage is Provoked by 4‐Methylpyrazole, which Prolongs the Influence of Ethanol but Reduces Acetaldehyde Levels
Authors: Lindros Kai O. , Sipponen Pentti , Pikkarainen Pekka , Turunen Ulla , Salaspuro Mikko
Published: February 2008

Rats chronically led ethanol developed liver injury only if they also received low doses of the alcohol dehydrogenase inhibitor, 4‐methylpyrazole, suggesting that the consistency of the influence of ethanol and its metabolism, rather than the level of acetaldehyde or the degree of the metabolic effects, contributes to the pathogenesis of alcoholic liver damage.
Utilization of Medical Services by Alcoholics Participating in an Outpatient Treatment Program
Authors: Sherman Richard M. , Reiff Sidney , Forsythe Alan B.
Published: February 2008

Utilization of medical services by alcoholics participating in an outpatient alcoholism treatment program was examined, comparing these with alcoholics who chose not to participate.
Alterations in Zinc, Vitamin A, and Retinol‐Binding Protein in Chronic Alcoholics: A Possible Mechanism for Night Blindness and Hypogonadism
Authors: McClain Craig J. , Thiel David H. Van , Parker Shirley , Badzin Laurie K. , Gilbert Howard
Published: February 2008

Deficiencies in zinc and vitamin A may play a role in the night blindness and hypogonadism of some chronic alcoholics; abstinence and zinc and vitamin A therapy may be of some benefit in these processes.
On Being the Offspring of an Alcoholic: An Update
Authors: El‐Guebaly Nady , Offord David R.
Published: February 2008

Reporting on research advances in a previous review of the literature, this article discusses the relative lack of controlled and prospective studies, the need for more treatment resources, the vulnerability of children of alcoholic parents compared to those of parents with other psychiatric diagnoses, and speculates on the sources of strength of the competent child of alcoholic parents.
Experimental Fibrogenesis: Enhancement by Chronic Ethanol Administration
Authors: Orrego H. , Israel Y. , Tiefenbach H. , Saldivia V. , Varghese G. , Medline A.
Published: February 2008

The authors have presented a new, simple, and reproducible model of fibrogenesis and have shown that chronic alcohol treatment clearly stimulates the production of fibrous tissue in this model.
Effect of Disulfiram on Cognition, Subjective Response, and Cortical‐Event‐Related Potentials in Nonalcoholic Subjects
Authors: Peeke Shirley C. , Prael A. Ruth , Herning Ronald I. , Rogers Walter , Benowitz Neal L. , Jones Reese T.
Published: February 2008

The effect of 0.5 g of disulfiram per day for 2 wk on a battery of cognitive and corticalevent‐related potential tasks was studied in healthy, nonalcoholic volunteers.
Disulfiram‐Induced Disturbances in Hypothalamic‐Pituitary Function
Authors: Thiel David H. Van , Gavaler Judith S. , Paul Gwendolyn M. , Smith William I.
Published: February 2008

This report indicates that disulfiram at clinically useful doses is capable of altering the hypothalamic‐pituitary‐gonadal function of normal men.
Influence of Chronic Ethanol Vapor Inhalation on Hepatic Parenchymal and Kupffer Cell Function
Authors: Luzio N. R. Di , Stege T. E.
Published: February 2008

This report evaluates the influence of chronic ethanol vapor inhalation on various facets of liver function as well as induction of hepatic and pulmonary pathology in rats. Chronic ethanol inhalation is associated with minimal hepatic dysfunction, but pronounced induction of metabolic tolerance.
Result of a Low‐Cost Follow‐Up Study of Discharged Alcoholics
Authors: Kern Joseph C. , Schmelter William R.
Published: February 2008

This paper describes a simple procedure for determining which variables in treatment programs are related to treatment outcome.
Cupro‐Zinc Superoxide Dismutase:A Possible Biologic Marker for Alcoholism (Studies in Black Patients)
Authors: Villano Bert C. Del , Tischfield J. A. , Schacter Lee P. , Stilwil David , Miller Sheldon I.
Published: February 2008

Cupro‐zinc superoxide dismutase (SOD‐1) was measured by competition radioimmune assay of erythrocyte lysates of alcoholic and control subjects. Normal amounts of SOD‐1 were found in the extract from control subjects (815 ng/mg Hb) and from white alcoholics (874 ng/mg Hb). However, the level of SOD‐1 in lysates from black alcoholics (1033 ng/mg Hb) was significantly increased (p= 0.0001, rank‐sum test) compared with black and white controls. This increase was not related to any other observed hematologic disorder or to any historical, demographic, or laboratory value examined.
Toward a Rapprochement of Empirical and Clinical Inquiry in Evaluation of Psychologically Oriented Alcoholism Treatment
Authors: Athey George I. , Coyne Lolafaye
Published: February 2008

The need to synthesize clinical and empirical considerations in naturalistic studies of psychologically oriented alcoholism treatment is discussed. Well done naturalistic studies are viewed as a necessary complement to more traditional controlled studies of treatment in order to maintain an interface of clinical reality with scientific respectability. A general clinical framework and scientific model for naturalistic study are proposed by which scientific and clinical considerations may be reconciled.
Effect of Modification of Brain Serotonin (5‐HT) on Ethanol Tolerance
Authors: Khanna J. M. , Kalant H. , Le A. D. , LeBlanc A. E.
Published: February 2008

The effects of 5,7‐dihydroxytryptamine and L‐tryptophan treatment on ethanol tolerance in the rat, as measured by the moving‐belt test of motor impairment and by hypothermia, were examined in separate studies. A 2 × 2 design was used for all experiments. 5,7‐Dihydroxy‐tryptamine (200 μg in 20 μl CSF) or vehicle alone was administered once into both lateral ventricles of the rat. Desmethylimipramine was administered intraperitoneally prior to an intraventricular injection of 5,7‐dihydroxytryptamine to prevent the destruction of norepinephrine. L‐Tryptophan (75 mg/kg p.o. twice daily) or water was administered chronically. Ethanol (4‐5 g/kg p.o.) or sucrose was given daily, and the development of tolerance was monitored at5–7‐day intervals. Chronic ethanol treatment produced tolerance to both the motor impairment and hypothermia effects of ethanol. 5,7‐Dihydroxytryptamine and L‐tryptophan treatment did not alter either the motor impairment or hypothermia produced by the initial dose of ethanol. 5,7‐Dihydroxytryptamine produced a 75% depletion of brain 5‐HT and slowed the development of tolerance to ethanol in both measurements. In contrast, elevation of 5‐HT by L‐tryptophan (39% increase by a single dose) facilitated the development of tolerance to ethanol, as seen in both measures. These findings support our hypothesis that brain 5‐HT has a modulating role in the development of tolerance to ethanol.
Problems and Pitfalls in Acetaldehyde Determinations
Authors: Eriksson C. J. Peter
Published: February 2008

The determination of acetaldehyde in biologic samples is complicated by a variety of formation and disappearance reactions occurring in the present methods of acetaldehyde analyses. The acetaldehyde formation (ethanol oxidation) in deproteinized supernatant of tissue preparations is prevented by the use of thiourea. During deproteinization, however, it is not inhibited by thiourea, and this remains the main problem in blood acetaldehyde determinations. To circumvent this problem, the use of a correction curve is proposed which is generated by adding control blood samples to the deproteinizing agent such that the blood dilution, temperature, and the ethanol concentrations (the main factors affecting the artifactual acetaldehyde formation) in the controls are identical to those of the samples. Disappearance reactions mainly include loss of acetaldehyde due to binding and/or metabolism. The problem seems to be pronounced with human blood samples, and it is recommended that they be rapidly (<5 sec) deproteinized.
Concentration Dependency of Ethanol Elimination Rates in Baboons: Effect of Chronic Alcohol Consumption
Authors: Pikkarainen P. H. , Lieber C. S.
Published: February 2008

Ethanol elimination rates were measured in 7 baboons fed alcohol for 2–7 yr (and their controls) by using a constant ethanol infusion to maintain blood ethanol at three different levels; 5, 10, and 50 mM. Ethanol elimination rates were significantly faster at a blood ethanol level of 50 mM than at 10 or 5 mM in both alcohol‐fed and control animals. The difference between 50 mM and 5 mM concentration was 36% in alcohol‐fed and 25% in control animals. In baboons fed ethanol chronically, the ethanol elimination rates were significantly faster than in pair‐fed controls at 50 mM (179 ± 10.0 mg/kg/hr versus 144 ± 9.8) and at 10 mM (148 ± 4.1 versus 114 ± 8.2), but not at 5 mM. Even if one takes into account the extrahepatic losses, these differences cannot be explained solely by the elimination of ethanol through the low Km alcohol dehydrogenase pathway, and these observations indicate that a non‐ADH system significantly contributes to ethanol elimination in vivo, especially in alcohol‐fed baboons.
Endocrine Effects of Maternal Alcoholization: Plasma and Brain Testosterone, Dihydrotestosterone, Estradiol, and Corticosterone
Authors: Kakihana Ryoko , Butte John C. , Moore Jerome A.
Published: February 2008

Maternal ethanol consumption was associated with reduced levels of dihydrotestosterone in the brains of 1–2‐day‐old male rats when compared to those of sex‐matched pups obtained from dames that were fed sucrose. In contrast, brain levels of corticosterone were increased significantly in the pups of ethanol‐fed animals when compared to those from sucrose‐fed controls. Brain and plasma estradiol did not differ between groups. These results suggest that maternal ethanol consumption may influence the central nervous system and plasma levels6000 of certain steroidal hormones in the offspring.
Demonstration of Tolerance to Ethanol in Non‐Nervous Tissue: Effects on Vascular Smooth Muscle
Authors: Altura Bella T. , Pohorecky Larissa A. , Altura Burton M.
Published: February 2008

Rats were maintained on liquid diets containing ethanol (6.8% v/v) or sucrose (controls) for periods of 2 and 6 wk to determine whether excised aortic or venous (portal vein) smooth muscle would exhibit any change in tone or reactivity when exposed to vasoactive agonists or to added ethanol (ETOH) in vitro. The results indicate that portal veins (PV) from the 2‐wk ETOH group show marked attenuation of (A) spontaneous tone, (B) angiotensin and K+‐induced contractions, and (C) Ca2+‐induced contractions. In contrast, PV from rats on ETOH for 6 wk only show depression of tone and Ca2+‐induced responses when compared to sucrose‐fed controls. Exposure of the PV to ethanol in vitro inhibits spontaneous tone of control sucrose‐fed animals but exerts little action on PV obtained from ETOH‐maintained rats. Although the addition of a high bathing concentration of ETOH (430 m/W) can evoke potent contractions in normal aorta, it fails to exert such action in most aortas obtained from rats maintained on ETOH. In vitro ETOH also dose‐dependently inhibited all drug‐induced contractions of blood vessels from control rats, but exerted little inhibition on PV and aortas obtained from ETOH‐maintained rats. These data indicate (1) chronic ETOH ingestion can directly influence vasomotor tone, reactivity of vascular muscle, and permeability of vascular membranes to Ca2+; (2) chronic ETOH treatment can induce a progressive “tolerance” in vascular tissue; and (3) the development of tolerance in vascular smooth muscle to ETOH may aid in explaining why long‐term alcoholic animals and man do not develop signs of hypotension.
Characterization of Acute and Chronic Tolerance in Mice Selected for Inherent Differences in Sensitivity to Ethanol
Authors: Tabakoff Boris , Ritzmann Ronald F. , Raju T. S. , Deitrich Richard A.
Published: February 2008

Long sleep (LS) and short sleep (SS) mice have been selectively bred for differences in response to hypnotic doses of ethanol. In these studies, SS mice were found to develop functional tolerance faster than LS mice during a regimen of multiple injections of ethanol. No evidence for the development of acute tolerance was evident in mice of either of the selected lines or the offspring of an LS by SS cross (F.), and no metabolic tolerance developed during the 5‐day alcohol treatment period.
Enhancement of Host Susceptibility to Staphylococcus aureus Infection by Chronic Ethanol Ingestion–Modification by Glucan Immunostimulation
Authors: Luzio Nicholas R. Di , Williams David L.
Published: February 2008

The susceptibility of chronic ethanol‐treated mice to S. aureus infection was ascertained, as was the ability of the immunostimulant glucan to modify ethanol‐induced susceptibility to infection. Chronic alcohol‐treated mice showed enhanced sensitivity to S. aureus. The administration of glucan significantly prolonged survival in S. aureus infected control and chronic ethanol mice.
The Metabolism of 14 C‐Disulfiram by the Rat
Authors: Neiderhiser Dewey H. , Fuller Richard K.
Published: February 2008

After administration of 14C‐disulfiram to rats by stomach tube, we found that 87% of the radioactivity was excreted in urine and 7% in feces. Greater than 80% of the radioactivity was excreted by 48 hr. Small but measurable radioactivity was excreted in urine up to 144 hr after administration. Total recovery of radioactivity at 144 hr was 95% of the ingested dose with less than 1% in organs, blood, and carcass; the remainder was in urine and feces. Studies on specific radioactivity showed that diethylamine, a major urinary metabolite of disulfiram, is excreted in the urine undiluted with endogenous diethylamine. Pretreatment of rats with unlabeled disulfiram leads to a more rapid catabolism of the radioactive drug and more rapid excretion of radioactivity in the urine. Further, pretreatment appears to induce formation of a glucuronide conjugate of a disulfiram metabolite.
Life‐Table Analysis of Abstinence in a Study Evaluating the Efficacy of Disulfiram
Authors: Fuller Richard K. , Williford William O.
Published: February 2008

Data from a study evaluating the efficacy of disulfiram for the treatment of alcoholism were analyzed by life‐table methods. Previous analysis by more commonly used statistical tests showed a trend favoring disulfiram treatment, but the results were not statistically significant. Life‐table methods are the appropriate techniques for analyzing longitudinal studies because they evaluate response to treatment over time rather than at one point in time. Analysis of our data using these methods revealed that disulfiram, combined with medical care and counseling, was superior to medical care and counseling alone in 128 men followed for 1 yr. This report demonstrates: (A) the advantage of life‐table methods for evaluating treatment outcome data in alcoholism studies; and (B) the importance of disulfiram treatment in alcoholic patients similar to those we studied.
One Year Follow‐Up of Total Abstinence in Chronic Alcoholic Patients Following Emetic Counterconditioning
Authors: Neubuerger Otto W. , Matarazzo Joseph D. , Schmitz Robert E. , Pratt Herbert H.
Published: February 2008

The present study is a crossvalidation in the Fair Oaks Raleigh Hills Hospital of a 1970 outcome study by Wiens et al. from the Portland Raleigh Hills Hospital. The 1975 Fair Oaks crossvalidation sample included all 275 patients treated during 1975. These results were further recrossvalidated using all 290 patients treated in the Fair Oaks hospital during 1976. Results were 12‐mo abstinence levels of 63% for the 1970 Portland sample and 39% and 50%, respectively, for the two Fair Oaks cross‐validation samples. If the more stringent total abstinence without a slip of a single drink was the outcome measure used, these 1975 and 1976 12‐mo abstinence levels became 33% and 43%, respectively. Additional analyses revealed the important role in these outcome rates of such demographic variables as Medicare recipient status, marital status, employment status, and a combined status of married and employed.
The Role of Alcohol Metabolism in the Effect of Ethanol on Protein Synthesis in Isolated Rat Hepatocytes
Authors: Mjirland Jørg , Bessesen Atle , Svendsen Lene
Published: February 2008

Rat liver parenchymal cells were isolated and incubated for 1–2 hr in a buffered salt solution. The addition of increasing concentrations of ethanol (10–105 mM| to the suspensions was accompanied by a dose‐dependent reduction (5%‐60%) of 14C‐valine incorporation into medium and cell proteins. Ethanol metabolism by alcohol dehydrogenase (ADH) was maximal between 10 and 20 m/W ethanol and did not increase at higher ethanol concentrations. Four‐methylpyrazole (4‐MP) (0.5 m/W), which inhibited ADH. abolished the inhibitory effect of low concentrations of ethanol (8 m/W) on valine incorporation, while it could not prevent the. inhibition caused by higher concentrations of ethanol (16 and 65 m/W). D‐Penicillamine (2 and 4 m/W), which complexes acetaldehyde, did not influence the inhibitory effect of ethanol on valine incorporation into protein. Additions of acetate (5 and 10 m/W) or sorbitol (3.5 and 5 m/W) were not able to mimic the effect of ethanol, as neither could reduction of medium pH from 7.4 to 7.0. Propanol (6–32 m/W) as well as tertiary butanol (5 and 10 m/W) inhibited valine incorporation into protein in a dose‐dependent manner. When ethanol was added to hepatocytes prepared from animals fed ethanol for 6 wk, the same inhibition of valine incorporation into protein was found as for cells from previously untreated rats. It was concluded that the inhibition of valine incorporation into liver proteins, which previously has been shown to be due to reduced protein synthesis, may occur in two ways. Low concentrations of ethanol appear to exert its effect through ethanol metabolism, while probably a direct effect of ethanol (and other alcohols) becomes increasingly important as the alcohol concentration rises.
A Study of the Calcium Carbimide‐Ethanol Interaction in Man: Symptom Responses
Authors: Peachey J. E. , Brien J. F. , Loomis C. W. , Rogers B. J.
Published: February 2008

Oral administration of ethanol up to 24 hr following calcium carbimide (CO. 0.7 mg/kg, produced an increase in blood acetaldehyde level, tachycardia, and increased pulse pressure due mainly to decrease in diastolic blood pressure, with reports of palpitations, shortness of breath, and facial warmth by most subjects. Positive linear correlations existed between acetaldehyde level and physiologic changes and acetaldehyde level and symptom responses, but there was appreciable individual variability in these responses. The magnitude and duration of chemical and physiological changes were greatest for the 4‐hr CC pretreatment interval and the 0.5 g/kg ethanol dose. For the 12‐hr CC pretreatment interval, symptoms were reported for the times of increased acetaldehyde level and as the CC pretreatment interval was shortened, symptom responses were intense but more variable. Symptom response ceased before the acetaldehyde level decreased below 4.0 g/ml and the heart rate declined below 100 beats/min. Symptom responses were significant compared to control for the 0.5 g/kg ethanol dose only. Two of 11 subjects expressed the desire for more ethanol during the 0.5 g/kg ethanol‐12‐hr CC pretreatment interaction. The results are discussed with respect to the clinical use of CC in alcoholism treatment.
Neuropsychologic Decrements as a Function of Alcohol Intake in Male Students
Authors: Parker Elizabeth S. , Birnbaum Isabel M. , Boyd Rosemary A. , Noble Ernest P.
Published: February 2008

Drinking history and sober neuropsychologic performance were examined in 45 male university students between the ages of 21 and 30 yr. Sober performance on the Shipley‐Hartford Institute of Living Scale was significantly and inversely related to the amount of alcohol consumed per drinking event. Neither frequency of drinking nor lifetime alcohol consumption were significantly related to cognitive performance in controlled multiple regression equations. These findings emphasize the need for more information about the effects of social drinking on health.
Alcohol and Very Low Density Lipoprotein Synthesis and Secretion by Isolated Hepatocytes
Authors: Lakshmanan M. R. , Felver Michael E. , Veech Richard L.
Published: February 2008

Labeled leucine can be used to measure accurately the rate of both total and secretory protein synthesis by isolated hepatocytes if at least 1 mM leucine is added to the incubation medium, even in the presence of 50 mM ethanol. Using this technique it was found that ethanol caused a significant inhibition of very low density lipoprotein (VLDL) as well as total protein synthetic rates in hepatocytes from both fed and fasted rats. In contrast, a single acute oral dose of ethanol to fasted rats caused within 4 hr a threefold stimulation in the rate of VLDL synthesis without affecting the total protein synthetic rate in the hepatocyte system.
Propranolol and Chlordiazepoxide Effects on Cardiac Arrhythmias During Alcohol Withdrawal
Authors: Zilm D. H. , Jacob M. S. , MacLeod S. M. , Sellers E. M. , Ti.M.D. T. Y.
Published: February 2008

The pattern of cardiac arrhythmias and their treatment, by propranolol and chlordiazepoxide, during the first 48 hr of alcohol withdrawal has been studied. Prior to treatment, the incidence of serious and life‐threatening arrhythmias was found to be very low and uncorrelated with most biochemical parameters. Propranolol treatment, while efficacious in controlling arrhythmias, was limited due to its association with hallucinations. Chlordiazepoxide was associated with poor early control of arrhythmias. The combination of propranolol and chlordiazepoxide was found to perform best overall with substantial reductions in arrhythmias and the fewest treatment failures.
Alcoholism and Cerebral Atrophy: A Study of 50 Patients With CT Scan and Psychologic Testing
Authors: Lusins John , Zimberg Sheldon , Smokier Herbert , Gurley Katherine
Published: February 2008

A study of 50 alcoholic patients was carried out with CT scans of their brains and psychologic testing. These patients were alcohol and drug free, and without neurologic or psychiatric disorders at the time of the examinations. Fifty‐eight percent of the patients had cerebral atrophy. There was no correlation between the results of the psychologic testing and cerebral atrophy. The only factor that correlated to a significant degree with cerebral atrophy was the duration of problem drinking. Only the mean duration of problem drinking was statistically significantly longer in the patients with cerebral atrophy compared to those patients with normal CT scans. Implications of this finding of high prevalence of cerebral atrophy in alcoholics is discussed.
Identification of Alcohol Abuse: Thoracic Fractures on Routine Chest X‐Rays as Indicators of Alcoholism
Authors: Israel Y. , Orrego H. , Holt S. , Macdonald D. W. , Meema H. E.
Published: February 2008

In a retrospective study, rib and thoracic vertebral fractures were found to be present on postero‐anterior and lateral routine chest x‐rays of 57 (28.9%) of 198 alcoholic male patients and in 4 (1.8%) of 218 nonalcoholic male control subjects. The magnitude of the increased prevalence (16‐fold; p < 0.001) of rib and vertebral fractures in alcoholics suggest that routine chest x‐rays should be useful in the identification of problem drinking and may be used, along with other indices, in population screening for alcoholism.
The Effect of Alcohol on Dopamine Metabolism in the Caudate Nucleus of an Unanesthetized Monkey
Authors: Weiner H. , Myers R. D. , Simpson C. W. , Thurman J. A.
Published: February 2008

Previously it was shown that the acute administration of ethanol to the rat significantly alters the metabolism of the dopamine (DA) in liver but not in brain tissue. To extend this finding to the primate, two push‐pull perfusion cannulas were implanted in the regions of the left and right caudate nucleus of a Macaca nemistrina. After 14C‐DA was injected into the caudate, the site was perfused with an artificial CSF and the perfusate analyzed for the major metalolites of DA. Ethanol was then administered in a dose of 6 g/kg by the nasopharyngeal route. The results show that very little alteration occurs in the metabolism of DA during or postethanol intoxication.
Reduction of Alcohol Consumption During Pregnancy with Benefits to the Newborn
Authors: Rosett Henry L. , Weiner Lyn , Zuckerman Barry , McKinlay Sonia , Edelin Kenneth C.
Published: February 2008

Among a group of 69 pregnant women who drank heavily, 25 reduced alcohol consumption before the third trimester. Infants born to these women showed less growth retardation than did infants born to 44 women who continued to drink heavily throughout the pregnancy. Analysis of other risk factors showed little effect on outcome when third trimester drinking patterns were held constant. Identification and counseling of heavy‐drinking pregnant women should provide benefits for both the mother and her newborn.
Effects of Chronic Ethanol Administration on 02 Consumption in Whole Body and Perfused Liver of the Rat
Authors: Schaffer W. T. , Denckla W. D. , Veech R. L.
Published: February 2008

The effects of chronic ethanol consumption on thyroid hormone levels and the rates of whole animal and perfused liver oxygen consumption were determined to test the hypothesis that alcoholic liver damage is a result of thyroid mediated liver hypermetabolism (L. Videla, J. Bernstein, and Y. Israel: Biochem. J, 134: 507–514, 1973). Whole animal minimal oxygen consumption, a sensitive indicator of the effects of thyroid hormone (W. D. Denckla: J. Clin. Invest, 53:572–581, 1974) was unchanged in rats maintained 3 wk on a liquid diet containing 34% of the calories as ethanol (2.49 ± 0.06 ml of O2/min/1O0 g of fat‐free body weight) when compared to animals fed an equicaloric sucrose containing liquid diet (2.61 ± 0.20 ml of 02/min/100 g of fat‐free body weight) or Purina chow (2.50 ± 0.12 ml of O2/min/100 g of fat‐free body weight). Ethanol treatment lowered serum thyroxine (5.09 ± 0.20 pg/100 ml) compared to sucrose‐fed control rats (7.66 ± 0.40 pg/100 ml), while serum triiodothyronine was unaffected (59.3 ± 4.0 compared to 66.9 ± 3.1 ng/100 ml for controls). Measurement of O2 consumption in the isolated perfused rat liver showed no significant difference after chronic treatment with the ethanol diet compared to either the sucrose or chow control diets. Infusion of 10‐7 M norepinephrine into the perfusion medium resulted in an approximately 22% increase in O2 consumption in ethanol‐fed animal and sucrose controls, while a 31 % increase was observed for sucrose‐treated animals given 10 μg of T3/kg of body weight/day for 3 wk. These data indicate that T3 potentiates the ability of norepinephrine to increase O2 consumption. The data presented give no support to the concept that chronic ethanol ingestion results in hyperthyroidism or liver hypermetabolism and, consequently, the rationale for treatment of alcoholic hepatitis with the antithyroid drug, propylthiouracil, is incorrect (H. Orrego, H. Ka‐lant, Y. Israel, et al.: Gastroenterology, 76:105–115, 1979).
The Effects of Chronic Ethanol Ingestion on Ethanol Binding to Hepatic Cytochrome P‐450 and on Certain Hepatic and Renal Parameters in the “Long Sleep” and “Short Sleep” Mouse
Authors: Hjelle J. J. , Atkinson N. , Petersen D. R.
Published: February 2008

Male mice selected for genetic differences in ethanol‐induced sleep time, thereby designated long sleep (LS) and short sleep (SS), were treated with the Lieber‐DeCarli liquid diet for 25 days. This chronic ethanol treatment produced an increase in liver/body weight and kidney/body weight in SS mice only. In addition, chronic ethanol treatment produced significant increases in both LS and SS treated mice in in vivo ethanol elimination, hepatic cytochromes P‐450 and Bs, NADPH cytochrome c reductase and hepatic and renal 7‐ethoxycoumarin O‐de‐ethylase activity. Geno‐typic differences were observed in the magnitude of response of microsomal ethanol oxidation per mg of microsomal protein (SS > LS). Further, control LS and SS mice possessed substantially different activity of renal 7‐ethoxycoumarin O‐de‐ethylase. Both lines exhibited similar induced renal 7‐ethoxycoumarin O‐de‐ethylase activity after chronic ethanol ingestion. Ethanol binding spectra produced when ethanol was added to hepatic microsomes were examined using double reciprocal plots. Chronic ethanol ingestion produced genotypically related (LS > SS) increases in the absorbance change maximum per mg of microsomal protein. No significant changes in the spectral dissociation constant or absorbance change maximum per nM cytochrome P‐450 were observed following ethanol treatment.
Order of Appearance of Alcoholic Symptoms
Authors: Pokorny Alex D. , Kanas Tom , Overall John E.
Published: February 2008

An extensive alcoholism history questionnaire was administered individually to 102 alcoholics. The results were analyzed by averaging the mean age of first occurrence of each symptom for the whole group, and separately by focusing on the order of appearance within each individual subject. The results of these two approaches are presented and compared.
Effects of Ethanol on Hepatic Blood Flow in the Rat
Authors: Iturriaga Hernan , Bunout Daniel , Petermanri Margarita , Ugarte Guillermo , Israel Yedi
Published: February 2008

Hepatic blood flow measured by indocyanine green clearance was studied in rats after an acute intoxicating dose of ethanol (2 g/kg) or after chronic ethanol administration by feeding with alcohol liquid diets. Acute intoxication to normal animals did not modify hepatic blood flow. In chronically alcohol‐fed rats, hepatic blood flow was significantly decreased when measured after 15 hr of abstinence. If ethanol was not withdrawn and an acute dose of ethanol was given before the indocyanine green clearance, a decreased hepatic blood flow was not observed. It is suggested that the reduction of hepatic blood flow in recently abstinent chronically alcohol‐treated animals is related to the withdrawal syndrome.
Effect of Chronic Ethanol Feeding on Testicular Content of Enzymes Required for Testosteronogenesis
Authors: Chiao Yu‐Bin , Johnston David E. , Gavaler Judith S. , Thiel David H. Van
Published: February 2008

Ethanol is a known inducer of microsomal enzymes as well as a testicular toxin. In order to evaluate the effect of chronic ethanol ingestion upon the microsomal enzymes required for testosterone synthesis, we examined the activity of four testicular enzymes (3β‐hydrex‐ysteroid dehydrogenase/isomerase, 17α‐hydroxylase, 17,20‐lyase, and 17β‐hydroxysteroid dehydrogenase) in 14 pairs of adult chronic alcohol‐fed rats and their age‐matched isocaloric controls. Ethanol feeding enhanced the activity of 17,20‐lyase when expressed as either activity/mg of protein (p< 0.05) or activity/g of testis (p< 0.025). Similarly, the activity of 17α‐hydrox‐ylase was increased in testes of the alcohol‐fed animals (p < 0.025) compared to controls. In contrast, chronic ethanol feeding reduced total activity of 3β‐hydroxy‐steroid dehydrogenase/isomerase in alcohol‐fed animals (p< 0.05) compared to controls. No effect of ethanol feeding was seen on activity of 17β‐hydroxy‐steroid dehydrogenase. Based upon these studies we conclude that chronic ethanol ingestion (1) increases testicular 17α‐hydroxylase and 17,20‐tyase and (2) reduces 3β‐hydroxysteroid dehydrogenase/isomerase in rat testicular microsomes. Therefore, we would propose that the major effect of chronic ethanol ingestion upon the enzymes required for testosteronogenesis is the reduction of 3β‐hydroxysteroid dehydrogenase/ isomerase activity, the rate limiting step in sex steroid production from pregnenolone.
Fetal Exposure to Ethanol Enhances Pituitary‐Adrenal and Temperature Responses to Etanol in Adult Rats
Authors: Taylor Anna Newman , Branch Berrilyn J. , Liu Stephen H. , Wiechmann Allan F. , Hill Mary Ann , Kokka Norio
Published: February 2008

Long lasting effects of perinatal ethanol exposure were studied in adult rats who were the offspring of dams fed a 5.0% w/v ethanol‐containing liquid diet ad libitum or pair‐fed the isocaloric control diet during gestation weeks 2 and 3 or during postnatal week 1. Fetal exposure to ethanol reduced body weight of pups at birth unless the ethanol diet was supplemented with casein; neonatal exposure to the ethanol or pair‐fed diets, casein supplemented or not, reduced pup weights until day 21 postnatally when weights of all fetally or neo‐natalty exposed pups were normal. Between 52 and 120 days of age females were tested for pituitary‐adrenal and temperature responses to a challenge dose of ethanol. Prenatally ethanol‐exposed rats showed significantly higher plasma corticosterone titers and developed a greater hypothermia in response to an intraperitoneal injection of ethanol (0.75–1.5 g/kg) than did pair‐fed controls. Similar response enhancement did not occur in the postnatally ethanol‐exposed rats. Temporal patterns of blood ethanol levels after an intraperitoneal injection of ethanol (1.5 g/kg) were similar in prenatally ethanol‐exposed females and their pair‐fed controls. The data indicate that exposure to ethanol in utero exerts persistent effects on the offspring, rendering them more responsive to the hypothermic and pituitary‐adrenal activating effects of alcohol as adults.
An Evaluation of the Effects of Lithium in the Treatment of Chronic Alcoholism. II. Assessment of the Two‐Period Crossover Design
Authors: Peck Carl C. , Pond Susan M. , Becker Charles E. , Lee Kenneth
Published: February 2008

Analysis of self‐reported alcohol intake by alcoholic subjects participating in a two‐period crossover trial of lithium versus placebo failed to demonstrate a significant effect of lithium in reducing alcohol consumption. An appraisal of the adequacy of this study design to meet the original objective of the trial was undertaken. It was impossible under this study design to simultaneously and unequivocally estimate effects of treatment periods, drug carryover, sequence group and other period by treatment interactions in addiction to the lithium/placebo effects. Presence of one or more of these additional influences on the trial outcome not only complicated the interpretation of results but diminished the power of the trial design to test the major hypothesis of interest, that lithium could reduce alcohol intake. We conclude that the two‐period crossover design has serious drawbacks in this clinical trial setting and that alternative strategies need to be considered for future trials.
MembraneiBuffer Partition Coefficient for Ethanol in Dimyristoylphosphatidylcholine
Authors: Rowe Elizabeth S.
Published: February 2008

Phase transitions of dimyristoylphosphatidylcholine (DMPC) are followed using optical density measurements, as a function of aqueous ethanol concentration. The shift of the phase transition to lower temperatures is interpreted in terms of the thermodynamics of freezing point depressions. This analysis provides a partition coefficient of ethanol into DMPC of 0.07 liter of solution/kg membrane or 2.64 moles of solvent/mole of DMPC.