bluuebunny/crossref_metadata_2025 huggingface dataset:
Congenital Leukemia Cutis
Authors: Fender Anne B. , Gust Anthony , Wang Nancy , Scott Glynis A. , Mercurio Mary Gail
Published: February 2008

Abstract:  We describe a premature neonate who was born with pancytopenia and a single subcutaneous nodule on her right lower extremity. A biopsy specimen from the nodule demonstrated a dense infiltrate of pleomorphic mononuclear cells that extended throughout the dermis and into the subcutaneous tissue. Immunohistochemical stains and bone marrow examination confirmed a diagnosis of acute myelogenous leukemia. Cytogenetic studies on peripheral blood by G‐banding analysis revealed an abnormal karyotype of 46, XX, ins[inv(10)(p11.2q22.2);11](q22.2;q13.2q23.2). A split in the mixed lineage leukemia gene was identified by fluorescence in situ hybridization. Induction chemotherapy was started but was complicated by multiorgan failure. The patient died on the eleventh day of life. As leukemia cutis more typically presents as multiple infiltrative papules, nodules, or plaques, we stress the importance of including leukemia in the differential diagnosis of a solitary nodule in a neonate.
Sclerosing Sweat Duct Carcinoma in a 6‐Year‐Old African American Child
Authors: Nelson Peter S. , Bourgeois Kristal M. , Nicotri Thomas , Chiu Ernest S. , Poole Jeffrey C.
Published: February 2008

Abstract:  Sclerosing sweat duct carcinoma is a rare, locally aggressive adnexal tumor that frequently occurs on the face of middle‐aged adults, invades deeply, and has a propensity to recur. We report a rare instance of sclerosing sweat duct carcinoma occurring in a 6‐year‐old African American child and review the literature of this infrequently observed neoplasm.
Giant Ceribriform Intradermal Nevus on the Back of a Newborn
Authors: Quaedvlieg Patricia J.F. , Frank Jorge , Vermeulen Anton H.M. , Toonstra Johan , Van Neer Francoise J.M.A
Published: February 2008

Abstract:  A male newborn had a large cerebriform tumor covering his shoulders and almost the entire surface of his back. After exclusion of further abnormalities, the diagnosis of cerebriform intradermal nevus was made. This particular variant of giant melanocytic nevus should always be differentiated from cutis verticis gyrata, if located on the vertex. The clinical manifestation of cerebriform intradermal nevi as giant melanocytic nevi on the back is extremely rare, with only one instance reported to date. Such nevi are a therapeutic challenge, particularly if the skin lesion covers a large surface of the body, as in the patient presented here.
Giant Bilateral Becker Nevus: A Rare Presentation
Authors: Khatami Alireza , Seradj Mehran Heydari , Gorouhi Farzam , Firooz Alireza , Dowlati Yahya
Published: February 2008

Abstract:  A 14‐year‐old boy had giant confluent brown patches that were bilaterally distributed on his back, chest, and upper arms, and partially covered by dark coarse hairs. A clinical diagnosis of Becker nevus was made and confirmed histopathologically. We report this patient for the rarity of presentation. Different clinical features of Becker nevi, associated findings, differential diagnoses, and treatment options are discussed.
Neonatal Eosinophilic Pustulosis in a 2‐Month Old
Authors: Ladrigan Manasi Kadam , LeBoit Philip E. , Frieden Ilona J.
Published: February 2008

Abstract:  We describe a 2‐month‐old preterm neonate presenting with neonatal eosinophilic pustulosis, manifesting as grouped pustules on the cheeks, leukocytosis and marked blood eosinophilia, and histology demonstrating abundant eosinophils without follicular involvement. Complete resolution of his skin lesions occurred spontaneously by 4 months of age, paralleling a decline in his eosinophil count. We discuss the relationship of this eruption to other pustular disorders of infancy and hypothesize a mechanism that may initiate the eruption.
Hair Follicle Nevus in a 2‐Year Old
Authors: Motegi Sei‐ichiro , Amano Hiroo , Tamura Atsushi , Ishikawa Osamu
Published: February 2008

Abstract:  We report a 2‐year‐old boy with an elastic soft, flatly elevated, skin‐colored nodule on his nasal ala. Histologic examination revealed numerous small hair follicles in several stages of maturation in the dermis. Serial sections did not show any cartilage or a central epithelial lined cystic structure. Based on clinico‐pathologic findings, we diagnosed this lesion as a hair follicle nevus. Hair follicle nevus is quite rare. Histologically, it is very important not to find cartilage or a central epithelial lined cystic structure for distinction from an accessory auricle and from a trichofolliculoma, respectively. Awareness of the clinical and pathologic characterization of hair follicle nevus is an aid to a correct diagnosis.
Patch Testing: Another Steroid‐Sparing Agent to Consider in Children
Authors: Jacob Sharon E. , Burk Cynthia J. , Connelly Elizabeth Alvarez
Published: February 2008

Abstract:  The burden of children suffering from chronic severe dermatitis and especially from undiagnosed confounding allergic contact dermatitis can be overwhelming for not only the patients and their families but also for their dermatologists. We report our protocol for pediatric patch testing and three pediatric cases, with severe and recalcitrant dermatitis unresponsive to systemic therapies, in whom comprehensive patch testing played a key role in management. Comprehensive patch testing allowed for the culprit allergens to be detected and subsequently avoided. With strict compliance, we were able to cease the use of systemic immunosuppressive therapy. These cases illustrate the importance of patch testing in recalcitrant dermatitis within the pediatric population.
Linear Nevoid Hypertrichosis Without Underlying Hypopigmentation or Extracutaneous Abnormalities
Authors: SUCHTER MARK F. , KHAN MISBAH , MILGRAUM SANDY
Published: February 2008

Abstract:  An 8‐year‐old Caucasian girl presented with a linear patch of excessive hair growth involving her left posterolateral leg without any underlying hypopigmentation or associated abnormalities. This is an unusual presentation given that the literature describing nevoid hypertrichosis in a linear distribution is associated with either underlying skin or hair hypopigmentation or other extracutaneous manifestations.
Multiple Giant Pilomatricoma in Familial Sotos Syndrome
Authors: GILABERTE YOLANDA , FERRER‐LOZANO MARTA , OLIVÁN MARÍA JESÚS , COSCOJUELA CARMEN , ABASCAL MANUEL , LAPUNZINA PABLO
Published: February 2008

Abstract:  Cerebral giantism or Sotos syndrome consists of a pre‐ and postnatal overgrowth whose genetic basis are mutations and deletions of the nuclear receptor‐binding SET domain containing protein gene. These patients have an increased risk of developing neoplasms, especially in adulthood. We report a 9‐year‐old boy, diagnosed with familial Sotos syndrome, who had two pilomatrixoma, symmetrically located on both sides of the neck, measuring 4 cm in diameter. Genetic study of the tumor tissue showed deletion of exon 22 of the NSD1 gene, whereas β‐catenin gene mutations were not detected. To the best of our knowledge, presentation of multiple pilomatricomas with Sotos syndrome has never been reported. Therefore their association probably is incidental. Nevertheless, the unusual size of our patient’s pilomatricomas could be due to deletion of the NSD1 gene, which characterizes Sotos syndrome.
Response of Juvenile Circumscribed Pityriasis Rubra Pilaris to Topical Tazarotene Treatment
Authors: KARIMIAN‐TEHERANI DANIELA , PARISSA MASTAN , TANEW ADRIAN
Published: February 2008

Abstract:  We report juvenile circumscribed pityriasis rubra pilaris (type IV) in a 12‐year‐old Afghani girl in whom local therapy with tazarotene led to rapid, sustained remission. Tazarotene might be considered a useful treatment for circumscribed pityriasis rubra pilaris.
Nevirapine‐Induced Stevens–Johnson Syndrome in a Pediatric Patient
Authors: MASON ASHLEY R. , CORTES GIL Y. , POLLACK ROSS B.
Published: February 2008

Abstract:  Nevirapine is a non‐nucleoside reverse transcriptase inhibitor commonly used in human immunodeficiency virus‐1 multidrug regimens and associated with life‐threatening cutaneous reactions. Here, we report the successful use of intravenous immunoglobulin in a pediatric patient with Stevens–Johnson syndrome and highlight the risk of nevirapine usage in human immunodeficiency virus postexposure prophylaxis.
Transient Dermatographism Presenting Within the First 18 Hours After Birth in an Otherwise Healthy Newborn
Authors: LA SHELL MAJ MARK S. , TANKERSLEY LT COL MICHAEL S.
Published: February 2008

Abstract:  We present the first reported instance of transient dermatographism occurring within 18 hours after birth in an otherwise healthy term newborn. The infant’s dermatographism resolved without intervention or sequelae, and this report provides guidance for the clinician to follow when presented with similar presentations.
Congenital Syringocystadenoma Papilliferum
Authors: KARG ESZTER , KOROM IRMA , VARGA ERIKA , BAN GYULA , TURI SANDOR
Published: February 2008

Abstract:  We present a boy with a congenital, ulcerated nodule on the scalp. At birth, the lesion was considered to be the result of a traumatic injury, but a biopsy at the age of 6 months pointed to a diagnosis of syringocystadenoma papilliferum. We draw attention to the difficulty of identifying head lesions in young children from clinical signs alone.
The Disabled Doctors Program of Georgia
Authors: Talbott G. Douglas
Published: February 2008

Georgia's statewide medical society program to aid physicians suffering from the disease of chemical dependency, drug abuse and psychiatric disorders is presented and reviewed after one year of operation. Its applicability to other state's Disabled Doctors Programs is suggested. Though still administratively and operationally improving and evolving, the efficacy of the program is attested to by the fact that one physician per month is being placed back in practice.
Ethanol Withdrawal: Altered Ambient Temperature Selection in Rats
Authors: Brick John , Pohorecky Larissa A.
Published: February 2008

Ethanol withdrawal in rats previously on an ethanol‐containing diet for 6 wk resulted in prolonged (4–6 days) alteration in ambient temperature selection. When placed in a T‐maze with a cold (2° C), a neutral (19° C), and a warm (30° C) alley, control and ethanol‐imbibing animals chose to remain in the neutral alley. In contrast, during and up to 6 days after ethanol withdrawal, animals consistently preferred the warm alley of the T‐maze. The withdrawal animals showed less locomotor activity, but lack of mobility, differences in body temperature, and direct disturbances in central monoamines probably were not responsible for the warm‐alley preference. Impaired ambient temperature selection was less if animals were on the ethanol‐containing diet for only 2 wk. It is suggested that longer lasting hormonal and/or metabolic derangements were possibly responsible for the impaired ambient temperature selection by animals undergoing withdrawal from ethanol.
Disulfiram Therapy in Alcoholism: Patient Compliance Studied with a Urine‐Detection Procedure
Authors: Gordis Enoch , Peterson Karen
Published: February 2008

A simple urine test to verify disulfiram (Antabuse®) use has been developed. Compliance with disulfiram therapy was determined in 95 consecutive abstinent alcoholic patients in an outpatient clinic. All patients were allegedly taking disulfiram. Twenty percent of them were found not to be using the drug, even though they said they were. Disulfiram is unusual because it is probably the patient's belief that he is taking it that is therapeutic, not the action of the drug. Because of this, it is difficult to incorporate placebo controls and double‐blind procedures into studies of disulfiram efficacy. However, with any research design, no conclusions will be valid if based solely on patients' reports of use.
Education of Nonscientists About New Alcohol Research: Results of Two Types of Presentations Plus 6‐Month Follow‐up
Authors: Erickson Carlton K. , Wilcox Richard E. , Littlefield John H. , Hendricson William D.
Published: February 2008

Education of nonscientists by scientists is assumed to be beneficial for enhancing public understanding of the research process and increasing public excitement about science. However, evaluation of audience response to receiving such information has rarely been performed. In particular, the effectiveness of communicating new research on alcohol abuse and alcohol dependence has never been evaluated. Evaluation data in the present study show significant knowledge transfer, belief changes, and participant reports of possible behavioral changes in targeted audiences. These occur when alcohol researchers present basic neuropharmacological concepts and new neurobiological research to audiences consisting primarily of chemical dependency counselors, social workers, criminal justice workers, physicians, nurses, family, clergy, and others interested in alcohol‐related problems (defined as “clinicians” and the “reachable public”). Together, these results suggest that it is possible to change the beliefs, knowledge, and behavior of chemical dependency clinicians and the reachable public about alcoholism, its causes, and its treatment.
Antisocial Personality Disorder and Alcohol‐Induced Aggression
Authors: Moeller F. Gerard , Dougherty Donald M. , Lane Scott D. , Steinberg Joel L. , Cherek Don R.
Published: February 2008

This study compared the effects of alcohol on aggressive responding between subjects with antisocial personality disorder (ASPD) and subjects without ASPD. Eighteen alcohol drinking subjects (10 subjects without ASPD and 8 subjects with ASPD) underwent testing on a laboratory measure of aggression, the Point Subtraction Aggression Paradigm, after consumption of placebo and three doses of alcohol (0.25 g/kg, 0.5 g/kg, and 1.0 g/kg). There was a significant difference in the effect of alcohol on aggressive responding on the Point Subtraction Aggression Paradigm between subjects with ASPD and subjects without ASPD. Subjects with ASPD had a greater increase in aggressive responding after alcohol, compared with non‐ASPD subjects. There was no difference between the two groups in the effect of alcohol on monetary‐reinforced responding.
Genetic Correlation Between Performance on an Appetitive‐Signaled Nosepoke Task and Voluntary Ethanol Consumption
Authors: Logue Sheree F. , Swartz Roxanna J. , Wehner Jeanne M.
Published: February 2008

The present study used a signaled appetitive nosepoke task as a measure of behavioral control or impulsivity related to reward system function in mice and determined how impulsivity correlated with voluntary ethanol consumption. Thirteen inbred strains were trained to nosepoke for food rewards and eventually trained to nosepoke for reward when an auditory signal was presented. Efficiency in the signaled nosepoke task indicated the ability of the mice to withhold the nosepoke response until the signal to respond for a reward was given and was considered indicative of behavioral control or impulsivity. After completion of the nosepoke task, the mice were tested for ethanol consumption in a three‐bottle choice test at 3 and 10% (v/v) ethanol concentrations. Behavioral measures from the nosepoke task and ethanol consumption measures were correlated to determine a genetic relationship. High efficiency, the ability to withhold nosepoking until signaled, was negatively correlated with ethanol consumption. Thus, the strains who were better able to control their behavioral responding (i.e., less impulsive) consumed less ethanol, and strains who were more impulsive consumed more ethanol. This genetic relationship may be a mouse behavioral model for some of the neuropsychological traits demonstrated in human subjects who are family history‐positive for alcoholism.
Comparison of Carbohydrate‐Deficient Transferrin, Immunoglobulin A Antibodies Reactive with Acetaldehyde‐Modified Protein and Acetaldehyde‐Modified Albumin with Conventional Markers of Alcohol Consumption
Authors: Worrall Simon , de Jerseyy John , Wilce Peter A. , Seppa Kaija , Hurme Liisa , Sillanaukee Pekka
Published: February 2008

Carbohydrate‐deficient transferrin (CDT) has emerged as the best new marker for alcohol abuse. Recently plasma immunoglobulin A (IgA) reactivity with acetaldehyde (AcH)‐modified proteins, or the modified proteins per se, have been proposed as a markers for high levels of alcohol consumption. In this study, we have compared CDT, IgA reactivity with AcH adducts (IgA ASR), and AcH‐modified albumin with conventional markers of high alcohol intake in groups with well‐defined drinking histories. The plasma activity of ALT, AST, and γ‐glutamyltransferase increased steadily with increasing alcohol consumption. CDT and AcH‐modified albumin showed a similar pattern, whereas IgA ASR appeared only to be elevated after a threshold level of consumption had been reached. Neither CDT IgA ASR or AcH‐modified albumin correlated strongly with any of the conventional markers or each other. This study shows that CDT, IgA ASR, AcH‐modified albumin, and the conventional markers are not related, but suggests that the concurrent use of CDT and IgA ASR may lead to better identification of high alcohol intake.
Differences in Alcohol Expectancy Between Aggressive and Nonaggressive Social Drinkers
Authors: Bjork James M. , Dougherty Donald M.
Published: February 2008

Previous reports have shown that drinkers with aggressive personalities not only hold the strongest beliefs that alcohol facilitates aggressive behavior, but they also display the greatest increases in laboratory aggression after receiving alcohol. Given that several studies have demonstrated that a portion of the behavioral and subjective effects of alcohol are due to psychological expectancy, this study explored whether aggressive drinkers have elevated intoxication expectancies from laboratory beverages with unknown alcohol content. The rates of aggressive responses emitted in a money subtraction aggression model under baseline conditions were used to select an aggressive group and a nonaggressive group, each with five male and five female participants. Subjects then ingested and rated each of three placebo (1 ml alcohol) beverages administered hourly during a subsequent laboratory visit, and rated a series of three 0.35 g/kg of alcohol beverages the following day. Whereas nonaggressive subjects clearly discriminated the relative alcohol content of alcohol and placebo drinks, aggressive subjects gave progressively elevated shot equivalent ratings to placebo drinks, similar to their ratings of alcohol doses. However, despite similar self‐reported drinking histories, aggressive subjects reported anticipating only half the intoxication from the alcohol doses (and in fact achieved a lower peak breath alcohol concentration) than was expected by nonaggressive subjects.
What Do Physicians Know and Say about Fetal Alcohol Syndrome: A Survey of Obstetricians, Pediatricians, and Family Medicine Physicians
Authors: Abel Ernest L. , Kruger Michael
Published: February 2008

Pediatricians, obstetricians, and family practice physicians in Michigan were surveyed by mail for their knowledge and opinions about Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Effects (FAE). Physicians said that about 67% of their patients raised questions about drinking during pregnancy but only 2% specifically referred to FAS or FAE. Most physicians were uncertain about whether their colleagues were sufficiently aware of FAS, whether FAS could be diagnosed at birth, or if physicians were acquainted with the syndrome's major criteria. However, most believed FAS was not being overdiagnosed and believed that making a diagnosis of FAS at birth could lead to improved treatment of an affected child. Physicians also believed that physician counseling was a more effective way of reducing the incidence of FAS/FAE than warning labels. Forty‐one percent of the physicians placed the threshold for FAS at one to three drinks per day and 38% placed the threshold at one or fewer drinks a day. Thirty‐five percent placed the estimated incidence of FAS at 1 to 2 per 1000 in the United States. We conclude that physicians are in relative agreement about the effects of drinking during pregnancy and the value of physician counseling but are misguided as to what constitutes a true risk level of drinking as far as the etiology of FAS is concerned.
Effects of Abstinence and Family History for Alcoholism on Platelet Adenylyl Cyclase Activity
Authors: Menninger John A. , Barón Anna E. , Tabakoff Boris
Published: February 2008

Platelet adenylyl cyclase (AC) activity was measured in 32 alcohol‐dependent subjects and 27 control subjects who were categorized as either family history‐positive (FHP) or family history‐negative (FHN) for alcoholism. The interview and blood sample collections were performed shortly after cessation of heavy drinking in the alcoholic group, and repeat blood samples were obtained at the end of the first and second weeks of monitored abstinence. Control subjects received the same interview and provided blood samples at the time of the interview. When subjects were not segregated for FHP or FHN status, there were no statistically significant differences in basal, cesium fluoride (CsF)‐, orforskolin‐stimulated mean AC activities between the controls and the alcoholics, at study entry or with 1 or 2 weeks of abstinence. On the other hand, over the 2‐week course of sobriety from heavy drinking, the CsF‐stimulated AC activity of FHP alcohol‐dependent subjects decreased significantly (p = 0.03). FHP alcohol‐dependent subjects after 2 weeks of sobriety had significantly lower mean CsF‐stimulated AC activity than FHN controls (p = 0.04), whereas the FHN alcoholic subjects' CsF‐stimulated AC activity did not differ significantly from FHN controls at this point in time. When all subjects were pooled and then categorized as either FHP or FHN, there was a significant difference in mean CsF‐stimulated AC activity (p = 0.02) between the FHP and FHN subject groups. Genetic factors and abstinence appear to have roles in determining low platelet AC activity in alcoholic and nonalcoholic subjects. CsF‐stimulated platelet AC activity, in particular, appears to act as a trait marker for a genetic vulnerability to developing alcoholism, but recent heavy drinking in male alcoholics is a factor that can mask differences between FHP and FHN subjects.
Behavioral Outcomes among Children of Alcoholics During the Early and Middle Childhood Years: Familial Subtype Variations
Authors: Puttler Leon I. , Zucker Robert A. , Fitzgerald Hiram E. , Bingham C. Raymond
Published: February 2008

This study examined early behavioral outcomes among young children of alcoholics (COAs) as a function of differences in subtype of paternal alcoholism. Participants were 212 children (106 girls and 106 boys, ages 3 through 8) and both of their biological parents. Families were characterized as antisocial alcoholics, nonantisocial alcoholics, and nonalcoholic controls. There were significant familial subtype group differences on parent report measures of children's total behavior problems, externalizing behavior, and internalizing behavior, and on measures of children's intellectual functioning and academic achievement. In all instances, COAs had poorer functioning than controls. In the behavior problem domain, but not for the domain of intellectual functioning, children from antisocial alcoholic families had greater problems than children from nonantisocial alcoholic families. In addition to the subtype effects, boys had higher levels of behavior problems than girls in all three areas, and older children had more internalizing problems than younger children. Maternal functioning pertaining to lifetime alcohol problem involvement and antisocial behavior also contributed to child subtype differences in internalizing behavior. Results indicate that, even at very early ages, male and female COAs are heterogeneous populations that are distinguishable by way of familial subtype membership, as well as distinguishable from their non‐COA peers. Thus, findings underscore the need to consider the heterogeneity of alcoholism when looking at its effects on child development
Clinical Correlations with Carbohydrate‐Deficient Transferrin Levels in women with Alcoholism
Authors: Oslin David W. , Pettinati Helen M. , Luck Gary , Semwanga Ann , Cnaan Avital , O'Brien Charles P.
Published: February 2008

Carbohydrate‐deficient transferrin (CDT) has received increasing attention as a potential biological marker for heavy drinking or as an objective marker of relapse in patients who are treated for alcohol dependence. Previous studies have demonstrated the utility of CDT among men, but there are fewer and inconsistent reports on the utility of CDT among women. This study reports in a sample of 40 alcohol‐dependent women, the association between CDT levels, and several different types of measures of drinking intensity including frequency of heavy drinking. Although the majority of drinking indices correlated with CDT levels in men, among women, CDT levels were significantly correlated with the percentage of days of heavy drinking when heavy drinking day was defined as drinking 6 or more drinks per drinking day. The results also support an association between current menstrual function, CDT levels, and drinking indices. These findings suggest that the pattern of drinking (combining high frequency and high intensity) may be an important determinant of CDT levels in women with alcohol dependence, compared with men.
Alcohol Consumption in Emergency Room Patients and the General Population: A Population‐Based Study
Authors: Borges Guilherme , Cherpitel Cheryl J. , Median‐Morea Maria E. , Mondraon Lilian , Casanova Leticia
Published: February 2008

Our purpose was to obtain epidemiological measures of the association between habitual alcohol consumption, alcohol consumption before the event and alcohol abuse/dependence, and emergency room (ER) attendance compared to the general population in Pachuca‐Hidalgo, a city located in the central area of Mexico. The study was a population based case‐control design. Data consisted of breath samples to estimated blood alcohol concentration, as well as an interviewer‐administered questionnaire, collected on a 24‐hr basis, during the entire week, in each of the three main ERs of Pa‐chuca. Cases were all patients who visited the three main hospitals ERs during the study period, classified according to their status as an injured or noninjured (medically ill) patient (n= 1511). The general population sample (n= 920) serves as a comparison group for both types of patients. Injured patients in the ER sample were significantly more likely to report high frequency/high quantity of drinking during the last 12 months than the general population [odds ratio and 95% confidence intervals = 5.55 (1.72–17.97)] and to report drinking within 6 hr before the injury. These relationships did not hold for noninjured patients. Both types of patients were more likely to report high frequency of drunkenness during the preceding 12 months, to be positive for alcohol dependence and to report drug use. We found in the city of Pachuca, a large relationship between habitual alcohol consumption and ER injuries. These findings support associations of alcohol consumption and admission to an emergency room found in ER and general population studies in other countries. Due to the increases in the risk found for abuse/dependent in both injured and noninjured patients, they both would benefit with a brief intervention strategy for reducing their alcohol consumption.
Age‐Related Differences in Risks of Drinking and Driving in Gender and Ethnic Groups
Authors: Johnson Fred W. , Gruenewald Paul J. , Treno Andrew J.
Published: February 2008

We examine the extent to which empirically observed age‐related differences in rates of drinking and driving can be explained by concurrent differences in drinking patterns. Building on previous research showing significant age differences in drinking patterns between men and women and among three ethnic groups, Whites, Blacks, and Hispanics, our study considers whether there are unique gender and ethnic group differences in patterns of drinking and driving. Data were from 4395 respondents 12 to 80 years old in a general population survey of 20 urban areas in the United States. During the month preceding the interview, 1130 (25.7%) of all respondents had driven after having one or more drinks. Drinking pattern measures included drinking frequency, average drinking quantity, and the variance in the number of drinks consumed per occasion. To assess the relationships of drinking patterns to drinking and driving across age groups, two sets of analyses were conducted, one set in which age differences in drinking patterns were statistically controlled and one set in which they were not Although the statistical control for drinking patterns reduced age differences between gender and ethnic groups, it did not eliminate them. The reduction demonstrated that part of observed group differences in driving after drinking over age among gender and ethnic groups is due to age‐related differences in drinking patterns. However, despite controlling drinking patterns young respondents remained more likely to drink and drive. A supplementary analysis of self‐reported incidents of driving while intoxicated (i.e., driving after having five or mora drinks) further indicated that, controlling for drinking patterns, young respondents are most at risk.
The Human Innunodeficiency Virus Type I Tatt Protein Potentiates Ethanol‐Induced Neutrophil Functional Impairment in Transgenic Mice
Authors: Prakash Om , Zhang Ping , Xie Ming , Ali Manzoor , Zhou Peng , Coleman Roy , Stoltz David A. , Bagby Gregory J. , Shellito Judd E. , Nelson Steve
Published: February 2008

Neutropenia and impairment of neutrophil function are commonly observed in patients with human immunodeficiency virus (HIV) infections. The HIV regulatory protein Tat is known to exert immunosuppressive effects. Alcohol is known also to be an immunosuppressive factor, and as alcohol abuse is common among HIV infected hosts, both factors may interact in an additive or synergistic fashion to further impair the host defenses of these patients. In order to test this possibility, endotoxin‐induced neutrophil β2‐integrins CD11b and CD18 expression, phagocytosis, and hydrogen, peroxide generation were examined in normal and HIV‐1 Tat‐transgenic mice in the absence and presence of ethanol intoxication. Acute ethanol intoxication was induced in mice (body weight of 25 ± 1 g) by an intraperitoneal Op) injection of ethanol (3 g/kg, 20% in normal saline). Thirty min later, the animals were given an ip injection of endotoxin (20 tig in 0.2 ml of saline/mouse). Vehicle‐treated controls received an ip injection of saline without ethanol or endotoxin. Two hr after endotoxin administration, the animals were killed to determine neutrophil functions with flow cytometry. The baseline expression of CD11b and CD18 was similar in normal nontransgenic and Tat‐transgenic mice. Endotoxin administration significantly up‐regulated CD11b and CD18 expression in normal mice. This up‐regulation was suppressed in Tat‐transgenic mice. Ethanol intoxication inhibited endotoxin‐induced CD11b and CD18 expression in normal mice and totally abolished endotoxin‐induced C011b and CD18 expression in Tat‐transgenic mice. Neutrophil phagocytic activity in normal and Tat‐transgenic mice was similar. Ethanol intoxication produced a similar inhibition of phagocytosis in both study groups. Endotoxin suppressed phagocytosis in normal mice, and this suppression was more pronounced in Tat‐transgenic mice. Spontaneous and phorbol myristate acetate (PMA)‐stimulated hydrogen peroxide generation by circulating neutrophils (PMNs) were similar in normal and Tat‐transgenic mice. Neither ethanol nor endotoxin affected hydrogen peroxide generation by PMNs. These data show that both Tat and alcohol significantly impair PMN function, and this may be a mechanism leading to the increased susceptibility of the HIV‐infected host to bacterial infection.
Defensive Burying and Stress Gastric Erosions in Alcohol‐Preferring AA and Alcohol‐Avoiding ANA Rats
Authors: Sandbak Tone , Murison Robert , Sarviharju Maija , Hyytia Petri
Published: February 2008

The aim of this study was to investigate differences in shock‐prod induced defensive burying and vulnerability to stress gastric ulcerations in two lines of rats selectively bred for alcohol‐preference (AA) and alcohol‐avoidance (ANA). Alcohol‐naïve animals from the AA and ANA lines were tested in the shock‐prod defensive burying test and (after an interval of approximately 2 months) in a 75 min water‐immersion stress ulceratjon‐inducing procedure. The AA rats showed longer latencies (327.5 s) for burying after shock‐prod compared with the ANA animals (128.0 s). Furthermore, the ANA rats developed more stomach ulcerations (12.35 mm) compared with the AA rats (1.30 mm). Animals also differed based on whether they had been tested for defensive burying or not, with the tested animals showing less ulceration development than the control group. We hypothesize that the difference between AA and ANA rats is controlled by some common biochemical mechanism. One likely candidate is the dopaminergic system, which is involved in both the motivational effects of alcohol, as well as anxiety and stomach ulceration. In addition, the alcohol‐preferring strain seems to be less fearful and generally may be less sensitive to aversive stimuli, be it shock prod, the aversive properties of alcohol, or water immersion stress.
Effects of Chronic Ethanol Consumption and Withdrawal on the Neuroactive Steroid 3α‐Hydroxy‐5α‐pregnan‐20‐one in Male and Female Rats
Authors: Janis Gregory C. , Devaud Leslie L. , Mitsuyama Hiroki , Morrow A. Leslie
Published: February 2008

Prolonged alcohol (ethanol) consumption leads to the development of alcohol tolerance and cross‐tolerance to some benzodiazepines and barbiturates. In contrast, rats undergoing alcohol withdrawal are sensitized to the anticonvulsant effects of the endogenous GABAA receptor modulator, 3α‐hydroxy‐5α‐pregnan‐20‐one (3α, 5α‐THP). Alterations in endogenous, cerebral cortical levels of 3α, 5α‐THP during alcohol withdrawal could contribute to the observed sensitization to 3α, 5α‐THP. Therefore, this study investigated plasma and brain levels of 3α,5α‐THP, progesterone, and corticosterone during alcohol dependence and withdrawal in the rat. Plasma corticosterone, progesterone (a precursor of 3α,5α‐THP) and 3α,5α‐THP levels were unchanged in alcohol‐dependent animals. Cerebral cortical levels of 3α,5α‐THP decreased in dependent male animals, but not in dependent female rats. During alcohol withdrawal, plasma corticosterone and progesterone levels increased in male, but not female rats. However, neither plasma nor cerebral cortical 3α,5α‐THP levels were altered from control levels in male or female rats during alcohol withdrawal. Plasma and brain levels of 3α,5α‐THP were markedly higher in female compared with male rats. Cerebral cortical levels of 3α,5α‐THP during the diestrus phase of the estrus cycle were ˜4 to 6 ng/g, a concentration that may approach physiological relevance. These findings suggest that sensitization to 3α,5α‐THP during alcohol withdrawal is not mediated by elevations in brain levels of endogenous 3α,5α‐THP in male or female rats. However, elevations in circulating corticosterone and progesterone levels during ethanol withdrawal in male rats may underlie gender differences in allopreg‐nanolone sensitivity during ethanol withdrawal.
Dietary Magnesium Supplementation Attenuates Ethanol‐Induced Myocardial Dysfunction
Authors: Brown Ricardo A. , Crawford Michelle , Natavio Melissa , Petrovski Pauline , Ren Jun
Published: February 2008

Hypomagnesemia is positively correlated with a number of cardiovascular abnormalities and recent evidence suggests that magnesium supplementation prevents ethanol‐induced development of hypertension. The purpose of our study was to assess whether dietary magnesium supplementation effectively reverses or attenuates chronic ethanol‐induced cardiac dysfunction, both at the tissue and the cellular level. Therefore, the influence of dietary magnesium supplementation during chronic ethanol ingestion on the mechanical properties of cardiac muscle was studied using isolated papillary muscles and ventricular myocytes from rat heart. In addition, the acute effects of ethanol on cardiac muscle from animals chronically exposed to ethanol in the absence and presence of dietary magnesium supplementation were also examined. Chronic ethanol exposure caused significant cardiac, hepatic, and renal enlargement, increased systolic blood pressure, and produced hypomagnesemia. After chronic ethanol exposure, the baseline force generating capacity of papillary muscles was markedly depressed and was associated with a significant slowing in the maximum velocities of contraction and relaxation. By contrast, in isolated myocytes, long‐term ethanol exposure increased the extent of cell shortening associated with a significant reduction in the duration of relengthening and an increase in both the maximum velocities of shortening and relengthening. Dietary magnesium supplementation among animals chronically ingesting ethanol effectively normalized heart size, systolic blood pressure, and reduced plasma ethanol concentration. Magnesium supplementation also attenuated chronic ethanol‐induced depression of contractile force and increased the extent of cell shortening. As expected, acute ethanol exposure caused a dose‐dependent inhibition of both isometric force and isotonic shortening associated with a decrease in the intracellular calcium transient. However, the extent of the acute ethanol‐induced reduction in isometric force and isotonic shortening was always slightly greater among preparations from animals chronically exposed to ethanol. Dietary magnesium supplementation normalized the acute inhibitory action of ethanol on isometric force, isotonic shortening, and the intracellular calcium transient. Our results suggest that dietary magnesium supplementation may attenuate chronic ethanol‐induced alterations in baseline myocardial mechanical function and normalize the cardiac response to acute ethanol exposure.
Ethanol Inhibition of Insulin Signaling in Hepatocellular Carcinoma Cells
Authors: Banerje Kakoli , Mohry Leonhard , Wands Jack R. , de la Monte Suzanne M.
Published: February 2008

Chronic ethanol toxicity impairs liver regeneration, inhibits DNA synthesis, and mutes cellular responses to growth factor stimulation. Previous studies demonstrated that the adverse effects of ethanol are mediated by inhibition of tyrosyi phosphorylation of the insulin receptor and the insulin receptor substrate‐type 1 (IRS‐1). However, overexpression of IRS‐1 leads to increased DNA synthesis and cellular transformation due to constitutive activation of mitogen‐activated protein (MAP) kinase. The present study examines the effects of ethanol on insulin signaling through IRS‐1 in FOCUS hepatocellular carcinoma cells, which overexpress IRS‐1, to determine whether such ceils were resistant to the inhibitory effects of ethanol. The results demonstrated that ethanol treatment (100 mM) caused 30 to 50% reductions in the levels of insulin‐stimulated tyrosyi phosphorylation of the insulin receptor β‐subunit, tyrosyi phosphorylation of IRS‐1, phosphorylation of Erk2,association of phosphatidylinositol‐3 kinase with tyrosyl‐phosphorylated IRS‐1, and MAP kinase and phosphatidylinositol‐3 kinase activities. In contrast, ethanol treatment had no effect on epidermal growth factor‐stimulated tyrosyi phosphorylation of She. Corresponding with the pronounced inhibition of MAP kinase, ethanol treatment resulted in 30 to 50% reductions in the expression levels of two important insulin‐responsive genes: glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) and proliferating cell nuclear antigen (PCNA). The findings suggest that, in FOCUS hepatocellular carcinoma cells, which overexpress IRS‐1, ethanol treatment substantially inhibits IRS‐1 and MAP kinase signaling and growth‐associated gene expression, but has no effect on She phosphorylation, which activates p21ras through an IRS‐1 independent pathway.
Human μ‐Opioid Receptor Variation and Alcohol Dependence
Authors: Sander Thomas , Gscheidel Nicola , Wendel Birgit , Samochowiec Jerzy , Smolka Michael , Rommelspacher Hans , Schmidt Lutz G. , Hoehe Margret R.
Published: February 2008

μ‐Opioid receptor‐mediated neurotransmission is involved in the reward, tolerance, and withdrawal effects of alcohol. The present association study tested the hypothesis that the common Asn40Asp substitution polymorphism in the N‐terminal domain of the human fi‐opioid receptor (OPRM)confers vulnerability to subtypes of alcohol dependence. The genotypes of the AsrvWAsp substitution polymorphism were assessed in 327 German alcohol‐dependent subjects (according to ICD‐10) and in 340 control subjects of German descent, using an assay based on allele‐specific polymerase chain reaction. To select alcoholics with a presumed high genetic load, three subgroups were delineated, marked by (1) a family history of parental alcoholism (n= 114); (2) the inability to abstain from alcohol before the age of 26 years (n = 73); and (3) a history of alcohol withdrawal seizure or delirium (n= 107). The frequency of the Asp40 allele did not differ significantly between the controls [f(Asp40) = 0.078] and either the entire group of alcoholics [f(Asp40) = 0.107; p= 0.066], or the alcoholics with parental alcoholism [f(Asp40) = 0.114; p= 0.094], or the early‐onset alcoholics [f (Asp40) = 0.096; p= 0.471] or the alcoholics with severe withdrawal symptoms [f(Asp40) = 0.098; p= 0.350]. Our results do not provide evidence that the common Asn40Asp substitution polymorphism of the OPRMgene contributes a major effect to the pathogenesis of alcohol dependence. Key Words: Alcohol Dependence, OPRMfi‐Opioid Receptor, Association, Genetics.
Prenatal Ethanol Exposure Selectively Reduces the mRNA Encoding α‐1 Thyroid Hormone Receptor in Fetal Rat Brain
Authors: Scott Heather C. , Sun Grace Y. , Zoeller R. Thomas
Published: February 2008

Some of the developmental defects characteristic of congenital or experimental hypothyroidism are also observed in children or experimental animals prenatally exposed to ethanol, suggesting that a subset of neurological defects attributable to ethanol exposure are produced by interfering with thyroid hormone action. In this article, we tested whether an ethanol treatment regimen known to produce neurological damage in rats can alter the expression of the mRNAs encoding the thyroid hormone receptor isoforms (TR α‐1, TR α‐2, and TR α‐1) in the fetal rat brain neocortex and hippocampus. Rats were fed an ethanol‐containing diet beginning on gestational day (G) 6 and continuing until sacrifice on G15, G17, or G21; controls included animals pair‐fed a liquid control diet or fed lab chow. Ethanol selectively reduced the expression of TR a‐1 mRNA in the neocortex and hippocampus on G21, compared with pair‐fed and control fetuses. In contrast, pair‐feeding selectively reduced TR a‐2 mRNA in both neocortex and hippocampus on G21, and increased TR 0–1 mRNA on G17. These data support the hypothesis that ethanol may interfere with thyroid hormone action during fetal brain development In addition, these data indicate that ethanol and pair‐feeding exert independent effects on thyroid hormone receptor expression in the developing brain.
Early Alcoholic Liver Injury: Formation of Protein Adducts with Acetaldehyde and Lipid Peroxidation Products, and Expression of CYP2E1 AND CYP3A
Authors: Niemelä Onni , Parkkila Seppo , Pasanen Markku , Limuro Yuji , Bradford Blair , Thurman Ronald G.
Published: February 2008

The formation of protein adducts with reactive aldehydes resulting from ethanol metabolism and lipid peroxidation has been suggested to play a role in the pathogenesis of alcoholic liver injury. To gain further insight on the contribution of such aldehydes in alcoholic liver disease, we have compared the appearance of acetaldehyde, malondialdehyde, and 4‐hydroxynonenal adducts with the expression of cytochrome P‐450IIE1, and cytochrome P‐4503A enzymes in the liver of rats fed alcohol with a high‐fat diet for 2 to 4 weeks according to the Tsukamoto‐French procedure and in control rats (high‐fat liquid diet or no treatment). Urine alcohol and serum aminotransferase levels were recorded, and the liver pathology was scored from 0 to 10 according to the presence of steatosis, inflammation, necrosis, and fibrosis. The ethanol treatment resulted in the accumulation of fat, mild necrosis and inflammation, and a mean liver pathology score of 3 (range: 1 to 5). Liver specimens from the ethanol‐fed animals with early alcohol‐induced liver injury were found to contain perivenular, hepatocellular acetaldehyde adducts. Malondialdehyde and 4‐hydroxynonenal adducts were also present showing a more diffuse staining pattern with occasional sinusoidal reactions. In the control animals, a faint positive reaction for the hydroxynonenal adduct occurred in some of the animals fed the high fat diet, whereas no specific staining was observed in the livers from the animals receiving no treatment Expression of both CYP2E1 and CYP3A correlated with the amount of protein adducts in the liver of alcohol‐treated rats. Distinct CVP2E1 ‐positive immunohistochemistry was seen in 3 of 7 of the ethanol‐fed animals. In 5 of 7 of the ethanol‐fed animals, the staining intensities for CYP3A markedly exceeded those obtained from the controls. The present findings indicate that acetaldehyde and lipid peroxidatjon‐derived adducts are generated in the early phase of alcohol‐induced liver disease. The formation of protein adducts appears to be accompanied by induction of both CVP2E1 and CVP3A.
Respective Roles of Human Cytochrome P‐4502E1, 1A2, and 3A4 in the Hepatic Microsomal Ethanol Oxidizing System
Authors: Salmela Katja S. , Kessova Irina G. , Tsyrlov Ilya B. , Lieber Charles S.
Published: February 2008

The microsomal ethanol oxidizing system comprises an ethanolinducible cytochrome P‐4502E1, but the involvement of other P‐450s has also been suggested. In our study, human CYP2E1, CYP1A2, and CYP3A4 were heterologously expressed in HepG2 cells, and their ethanol oxidation was assessed using a corresponding selective inhibitor: all three P‐450 isoenzymes metabolized ethanol. Selective inhibitors‐4‐methylpyrazole (CYP2E1), furafylline (CYP1A2), and troleandomycin (CYP3A4)?also decreased microsomal ethanol oxidation in the livers of 18 organ donors. The P‐450‐dependent ethanol oxidizing activities correlated significantly with those of the specific monooxygenases and the immunochemically determined microsomal content of the respective P‐450. The mean CYP2E1‐dependent ethanol oxidation in human liver microsomes [1.41 ± 0.11 nmol min‐1 (mg protein)‐1] was twice that of CYP1A2 (0.61 ± 0.07) or CYP3A4 (0.73 ± 0.11) (p < 0.05). Furthermore, CYP2E1 had the highest (p < 0.05) specific activity [28 ± 2 nmol min‐1 (nmol CYP2E1)‐1 versus 17 ± 3 nmol min‐1 (nmol CYP1A2)‐1, and 12 ± 2 nmol min‐1 (CYP3A4)‐1, respectively]. Thus, in human liver microsomes, CYP2E1 plays the major role. However, CYP1A2 and CYP3A4 contribute significantly to microsomal ethanol oxidation and may, therefore, also be involved in the pathogenesis of alcoholic liver disease.