bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Risk Factors for Hepatocellular Carcinoma in Patients With HBs Antigen‐ and Anti‐HCV Antibody‐Negative Alcoholic Cirrhosis: Clinical Significance of Prior Hepatitis B Virus Infection
Authors: Uetake Shinichiro , Yamauchi Masayoshi , Itoh Shuji , Kawashima Osamu , Takeda Kunihiko , Ohata Mitsuru 
Published: November 2003

Background: The hepatitis B virus (HBV) or hepatitis C virus (HCV) markers frequently are detected in alcoholic patients with hepatocellular carcinoma (HCC). However, risk factors for the development of HCC in patients with HBs antigen (Ag)‐ and anti‐HCV antibody (anti‐HCV)‐negative alcoholic cirrhosis have not been clearly documented. The present study was conducted to elucidate the occurrence rates of HCC in HBs Ag‐ and anti‐HCV‐negative male alcoholic cirrhosis and to assess the risk factors for hepatocellular carcinogenesis.Method: We prospectively studied 91 consecutive patients with HBs Ag‐ and anti‐HCV‐negative alcoholic cirrhosis for 0.5 to 12.5 years (median 5.9 years). Potential risk factors assessed for liver carcinogenesis included the following six variables: age, total alcohol intake, association of continuing alcohol intake after diagnosis, indocyanine green retention rate at 15 min, anti‐HB core antibodies (anti‐HBc), and association of diabetes mellitus.Results: Cumulative occurrence rates of HCC were 6.4%, 18.9%, and 28.7% at the end of the 5th, 7th and 10th years, respectively. When classified by anti‐HBc, the occurrence rates of HCC in 31 patients with anti‐HBc and 60 patients without anti‐HBc were 15.6% and 2.9% at the 5th year, 28.4% and 13.5% at the 7th year, and 40.4% and 22.1% at the 10th year, respectively. The occurrence rates of HCC were also significantly related to the cumulative alcohol intake. Cox proportional hazard model identified that cumulative alcohol intake (p= 0.0047) and positive anti‐HBc antibodies (p= 0.0598) were independently associated with the occurrence rates of HCC.Conclusion: These epidemiologic results suggest that heavy cumulative alcohol intake and prior exposure to HBV infection are risk factors for the development of HCC in patients with HBs Ag‐ and anti‐HCV‐negative alcoholic cirrhosis.
Comprehensive Assessment of Insomnia in Recovering Alcoholics Using Daily Sleep Diaries and Ambulatory Monitoring
Authors: Currie Shawn R. , Clark Stewart , Rimac Stephen , Malhotra Sonya 
Published: November 2003

Background: Many alcoholics continue to experience disrupted sleep after quitting drinking. Previous studies with recovering alcoholics have relied on retrospective questionnaires and a single night of polysomnography to document sleep problems. In the present study, sleep was assessed at home over the course of a week using both subjective and objective sleep measures.Methods: A mixed gender group of alcoholics in recovery (n= 63) experiencing insomnia underwent a multimodal sleep assessment including a structured interview, daily sleep diaries, questionnaires, and ambulatory sleep monitoring. Alcoholics with short‐term (<12 months) and long‐term (>12 months) abstinence had their sleep monitored prospectively and were compared.Results: Over half of the participants reported sleep problems that predated the onset of alcohol dependence. Alcoholics with short‐ and long‐term abstinence had similarly disturbed sleep. Overall, problems with getting to sleep were worse than sleep maintenance difficulties. Severity of insomnia was unrelated to drinking history and modestly correlated with the current level of depressive symptoms. Poor sleep hygiene was evident in the sample.Conclusions: Alcoholics can experience sleep problems for many months after quitting drinking. Implications for sleep interventions with this population are discussed.
Methodological Characterization of the 2‐Keto [1‐13C]isocaproate Breath Test to Measure in Vivo Human Mitochondrial Function: Application in Alcoholic Liver Disease Assessment
Authors: Parra Dolores , González Alvaro , García‐Villarreal Luis , Martínez J. Alfredo 
Published: November 2003

Background: The 2‐keto[1‐13C]isocaproate oxidation measurement has been shown as a helpful tool in the in vivo assessment of liver mitochondrial function.Methods: The aim of this work was to study the variability of the 2‐keto[1‐13C]isocaproate breath test in 24 healthy controls (8 men and 16 women) and to evaluate its clinical usefulness in 20 patients (14 men and 6 women) with liver disease (7 men with history of alcoholism). Breath test was performed by measuring 13CO2 enrichment in breath before and after the oral administration of the tracer and by using isotope ratio mass spectrometry.Results: The intrasubject and intersubject variability of the percentage of tracer oxidized were 8 and 14%, respectively. The 2‐keto[1‐13C]isocaproate oxidation in women was faster (p= 0.004) and tended to be higher (p= 0.050) than in men. The percentage of oxidized tracer was lower in those patients with alcoholic liver disease than in healthy volunteers (p= 0.001) and in nonalcoholic patients (p= 0.003).Conclusions: The percentage of tracer oxidized appears as a convenient parameter to detect impairment in liver mitochondrial oxidation related to alcoholism by the 2‐keto[1‐13C]isocaproate breath test, establishing different cutoff values depending on gender.
Association Between Dopamine Receptor D1 Gene Dde I polymorphism and Sensation Seeking in Alcohol‐Dependent Men
Authors: Limosin Frédéric , Loze Jean‐Yves , Rouillon Frédéric , Adès Jean , Gorwood Philip 
Published: November 2003

Background: Among genetic and biopsychological factors involved in alcohol‐dependence vulnerability, dopamine receptor subtypes genes and temperament's dimensions, such as sensation seeking, have been particularly incriminated. Moreover, it is suggested that higher levels of sensation seeking could be associated with a modification of sensitivity to dopamine in postsynaptic receptors.Methods: We investigated whether the DRD1 Dde I polymorphism could be associated with the sensation‐seeking level among a sample of 72 alcohol‐dependent male and female patients. Analyses of variance were performed to test for an effect between the DRD1 Dde I genotypes and sensation‐seeking scores according to the 40‐item Zuckerman scale.Results: When comparing the DRD1 Dde I genotypes and the Zuckerman scores, we found a significant association only in men (p= 0.01).Conclusions: That is the first report of a male limited association between the DRD1 gene polymorphism and sensation‐seeking score in alcohol‐dependent subjects.
Alleles of a Functional Serotonin Transporter Promoter Polymorphism Are Associated With Major Depression in Alcoholics
Authors: Nellissery Maggie , Feinn Richard S. , Covault Jonathan , Gelernter Joel , Anton Raymond F. , Pettinati Helen , Moak Darlene , Mueller Timothy , Kranzler Henry R. 
Published: November 2003

Background: Serotonergic neurotransmission has been implicated in the pathogenesis of both alcohol dependence and mood disorders and may therefore be important in understanding the pathophysiology of comorbid alcohol dependence and major depression. Studies of the association of these disorders with a functional polymorphism in the promoter region of the gene encoding the serotonin transporter protein (locus SLC6A4) have yielded inconsistent results. Because the convergence of these disorders may provide a refined phenotype, we examined the association of serotonin (5‐HT) transporter linked polymorphic region (5‐HTTLPR) alleles to comorbid alcohol dependence and major depression.Methods: A sample of 296 European American and 16 African American patients with comorbid alcohol dependence and major depression was recruited from treatment studies. The control group included 260 European Americans and 43 African Americans; all were screened to exclude the presence of a mood or substance use disorder. DNA isolated from whole blood was polymerase chain reaction–amplified, and genotypes were assigned on the basis of agarose gel size fractionation.Results: The frequency of the short allele in the patient group was in the range of those previously reported for samples with unipolar depression but was significantly more common than among controls (short allele frequency of cases, 45.8%; controls, 39.8%; χ21= 4.02; p= 0.045).Conclusions: With respect to the frequency of the short allele at the SLC6A4 locus (5‐HTTLPR), major depression in alcoholics is similar to major depression in nonalcoholics. Further efforts to characterize depressed alcoholics and to examine genetic predictors of response to antidepressant treatment seem warranted.
Test‐Retest Reliability of the Alcohol Use Disorder Identification Test in a General Population Sample
Authors: Selin Klara Hradilova 
Published: November 2003

Background: A number of different screening tests are frequently used in alcohol research, but our knowledge about the reliability of many of them is quite limited. Recently, this problem has received more attention. This article examines the test‐retest reliability of one of these instruments—the Alcohol Use Disorder Identification Test (AUDIT)—in a general population sample.Methods: A general population sample (n= 457) was tested and, after approximately 1 month, was retested by using the AUDIT. Correlation between the two tests has been examined with the intraclass correlation coefficient and the κ coefficient in analysis of dichotomous variables. Specificity and sensitivity at a number of different cutoff scores have also been analyzed by using the first test as a criterion.Results: On the item level, the correlations ranged between 0.6 and 0.8. The overall reliability of total AUDIT scores was 0.84. When stratified by gender, age, and consumer status, the total score reliability approximated 0.80 for all the categories except low alcohol consumers (0.51). Agreement using the recommended cutoff score of 8+ was also examined. The reliability (κ) observed in the whole sample was 0.691, which was interpreted as a substantial agreement. By this cutoff, 91% were correctly classified at retest compared with the first test. AUDIT 8+ showed higher reliability for males, young people, and moderate consumers and low reliability among low consumers. In terms of reliability, the most optimal cutoff for women turned out to be 6 or more.Conclusions: According to these results, the test‐retest reliability of AUDIT is high. The next step might be to examine to what extent the findings apply within health‐care settings, which is what the test originally was designed for.
Effect of Ethanol on Reductions in Norepinephrine Electrochemical Signal in the Rostral Ventrolateral Medulla and Hypotension Elicited by I1‐Receptor Activation in Spontaneously Hypertensive Rats
Authors: Mao Limin , Li Guichu , Abdel‐Rahman Abdel A. 
Published: November 2003

Background: The mechanism of the antagonistic hemodynamic interaction between ethanol and centrally acting sympatholytics is not known. In this study, we tested the hypothesis that the imidazoline (I1)‐receptor modulation of norepinephrine (NE) release within the rostral ventrolateral medulla (RVLM) plays a pivotal role in this clinically relevant hemodynamic interaction.Method: In anesthetized spontaneously hypertensive rats, the effects of centrally acting sympatholytics on RVLM NE electrochemical signal were investigated by in vivo electrochemistry along with cardiovascular responses in the absence and presence of ethanol. In vivo microdialysis in conscious spontaneously hypertensive rats was used to confirm the electrochemical findings.Results: Clonidine (30 μg/kg, intravenously) or rilmenidine (400, 600, or 800 μg/kg) significantly reduced RVLM NE electrochemical signal (index of neuronal activity) and mean arterial pressure; rilmenidine effects were dose‐related, and ethanol (1 g/kg) counteracted these responses. Ethanol (1 g/kg) pretreatment increased both RVLM NE electrochemical signal and blood pressure but did not influence the reductions in both variables elicited by subsequently administered clonidine. The α2‐adrenergic antagonist 2‐methoxyidazoxan (30 μg/kg) counteracted rilmenidine (800 μg/kg)‐evoked responses. In vivo microdialysis in conscious spontaneously hypertensive rats confirmed the electrochemical findings since clonidine‐ (30 μg/kg, intravenously) evoked reductions in RVLM NE and the associated hypotension were counteracted by ethanol (1 g/kg).Conclusions: (1) Ethanol counteracts centrally mediated hypotension, at least in part, by increasing RVLM NE; (2) the interaction involves the I1 receptor modulation of RVLM neuronal activity; (3) the α2‐adrenergic receptor contributes to the electrochemical and cardiovascular effects of high doses of rilmenidine, and (4) the RVLM is a neuroanatomical target for systemically administered ethanol.
Psychometric Properties of the Short Index of Problems as a Measure of Recent Alcohol‐Related Problems
Authors: Feinn Richard , Tennen Howard , Kranzler Henry R. 
Published: November 2003

Background: The Drinker Inventory of Consequences (DrInC) measures overall consequences of drinking and yields five subscale scores. A short form of the DrInC, the Short Index of Problems (SIP), was developed for use when time does not permit completion of the DrInC. This study investigates the psychometric properties of the SIP.Methods: The study sample consisted of 153 problem drinkers who were participants in a placebo‐controlled trial of naltrexone and brief counseling.Results: The SIP showed good internal consistency, good concurrent validity, and adequate stability. Four of the five SIP subscales contributed unique variance beyond general drinking consequences.Conclusions: The SIP is useful for measuring drinking consequences in a sample of problem drinkers, and the subscale scores can be interpreted clinically. Further research on the SIP in other populations is warranted.
Ethanol Modulation of Excitatory and Inhibitory Synaptic Transmission in Rat and Monkey Dentate Granule Neurons
Authors: Ariwodola O. J. , Crowder T. L. , Grant K. A. , Daunais J. B. , Friedman D. P. , Weiner J. L. 
Published: November 2003

Background: The physiological mechanisms underlying the behavioral and cognitive effects of ethanol are not fully understood. However, there is now compelling evidence that ethanol acts, at least in part, by modulating the function of a small group of proteins that mediate excitatory and inhibitory synaptic transmission. For example, intoxicating concentrations of ethanol have been shown to enhance GABAergic synaptic inhibition and depress glutamatergic excitatory neurotransmission in a number of brain regions. Because all of these electrophysiological studies have been performed in rodent brain slice or neuronal culture preparations, direct evidence that ethanol exerts similar effects on synaptic transmission in the primate central nervous system is lacking.Methods: We have therefore developed methods to perform patch‐clamp electrophysiological recordings from neurons in acutely prepared monkey (Macaca fascicularis) hippocampal slices. We have used these methods to compare the acute effects of ethanol on excitatory and inhibitory synaptic transmission in rat and monkey dentate granule neurons.Results: Under our recording conditions, ethanol significantly potentiated γ‐aminobutyric acid type A inhibitory postsynaptic currents in both rat and monkey neurons. In addition, ethanol significantly inhibited NMDA, but not AMPA, excitatory postsynaptic currents in dentate granule neurons from both species. Notably, no significant differences were observed in any of the pharmacological properties of inhibitory or excitatory synaptic responses recorded from rat and monkey neurons.Conclusions: These data suggest that the differences in the behavioral effects of ethanol that have been observed between rats and higher‐order mammals, such as monkeys and humans, may not reflect differences in the sensitivity of some of the major synaptic sites of ethanol action. Moreover, our results provide empirical evidence for the use of rodent brain slice preparations in elucidating synaptic mechanisms of ethanol action in the primate central nervous system.
Recommendations on Use of Biomarkers in Alcoholism Treatment Trials
Authors: Allen John P. , Litten Raye Z. 
Published: November 2003

Background: Biochemical markers of heavy drinking are playing increasingly prominent roles in alcohol treatment efficacy studies, especially in those designed to evaluate medications. Among these roles are serving as inclusion or exclusion criteria for research participants, corroboration of self‐report of drinking status, assessment of the safety of the agent being evaluated, and determination of treatment outcome.Methods: Recent alcohol medication development trials that included biomarker information were reviewed and critiqued from the perspectives of how biomarker measures were used and how findings on them were reported.Results: Although generally the application of biomarkers as inclusion criteria is not recommended, they may aid in exclusion of potential subjects (e.g., elevated liver function measures in trials of agents that could result in liver damage). Biomarkers are most commonly used as indicators of outcome, usually serving as secondary outcome variables. The relationship of outcome findings on biomarker and self‐report measures is positive, but only moderate. As used to date, biomarkers of drinking tend to be less sensitive than well‐standardized and properly administered self‐report measures. Nevertheless, they do provide a useful, unique source of information on drinking status.Conclusions: The contribution of biomarkers to alcoholism clinical research would be enhanced if certain design strategies were incorporated into their application and if critical information were included in the research publication. This article offers a series of recommendations to improve on their use in a research context.
Hypericum perforatum CO2 Extract and Opioid Receptor Antagonists Act Synergistically to Reduce Ethanol Intake in Alcohol‐Preferring Rats
Authors: Perfumi Marina , Santoni Manuela , Cippitelli Andrea , Ciccocioppo Roberto , Froldi Rino , Massi Maurizio 
Published: November 2003

Background: Hypericum perforatum extracts attenuate ethanol intake in alcohol‐preferring rats. The opioid receptor antagonists, naloxone and naltrexone, reduce ethanol intake in rats and humans. The combination of different agents that reduce ethanol intake has been proposed as an approach to the pharmacotherapy of alcoholism. This study evaluated the effect on ethanol intake of the combined administration of a CO2H. perforatum extract and naloxone or naltrexone in genetically selected Marchigian Sardinian alcohol‐preferring rats.Methods: Ten percent (v/v) ethanol intake was offered 2 hr per day at the beginning of the dark phase of the reverse light‐dark cycle. H. perforatum CO2 extract was given intragastrically, 1 hr before access to ethanol. Naloxone or naltrexone was given by intraperitoneal injection 10 min before the extract.Results: H. perforatum CO2 extract reduced ethanol intake at 31 or 125 mg/kg, but not 7 mg/kg. These doses neither modified food or water intake during access to ethanol, nor reduce 0.2% saccharin intake. Naloxone reduced ethanol and food intake at 3 or 5 mg/kg, but not 1 mg/kg. When naloxone 1 mg/kg was combined with the three doses of H. perforatum CO2 extract, the attenuation of ethanol intake was more pronounced than that observed after the administration of the extract alone. Alcohol intake was also significantly reduced by 7 mg/kg of H. perforatum CO2 extract combined with naloxone 1 mg/kg. The combined treatments never modified the rat's locomotor activity nor the simultaneous intake of food, water or 0.2% saccharin. Naltrexone reduced ethanol intake at 1 and 3 mg/kg, but not at 0.5 mg/kg. When naltrexone 0.5 mg/kg was combined with H. perforatum CO2 extract 7 mg/kg, ethanol intake was markedly reduced.Conclusions: These findings provide evidence that H. perforatum CO2 extract and opiate receptor antagonists act synergistically to induce a pronounced and selective reduction of voluntary ethanol consumption in alcohol‐preferring rats.
Conserved Nucleotides within the J Domain of the Encephalomyocarditis Virus Internal Ribosome Entry Site Are Required for Activity and for Interaction with eIF4G
Authors: Clark Angela T. , Robertson Morwenna E. M. , Conn Graeme L. , Belsham Graham J. 
Published: November 2003

ABSTRACT
The internal ribosome entry site (IRES) elements of cardioviruses (e.g., encephalomyocarditis virus [EMCV] and foot-and-mouth disease virus) are predicted to have very similar secondary structures. Among these complex RNA structures there is only rather limited complete sequence conservation. Within the J domain of the EMCV IRES there are four highly conserved nucleotides (A704, C705, G723, and A724)., which are predicted to be unpaired and have been targeted for mutagenesis. Using an IRES-dependent cell selection system, we have isolated functional IRES elements from a pool of up to 256 mutants. All changes to these conserved nucleotides resulted in IRES elements that were less efficient at directing internal initiation of translation than the wild-type element, and even some of the single point mutants were highly defective. Each of the mutations adversely affected the ability of the RNAs to interact with the translation initiation factor eIF4G.
Rise and Survival of Bovine Herpesvirus 1 Recombinants after Primary Infection and Reactivation from Latency
Authors: Schynts Frédéric , Meurens François , Detry Bruno , Vanderplasschen Alain , Thiry Etienne 
Published: November 2003

ABSTRACTRecombination is thought to be an important source of genetic variation in herpesviruses. Several studies, performed in vitro or in vivo, detected recombinant viruses after the coinoculation of two distinguishable strains of the same herpesvirus species. However, none of these studies investigated the evolution of the relative proportions of parental versus recombinant progeny populations after coinoculation of the natural host, both during the excretion and the reexcretion period. In the present study, we address this by studying the infection of cattle with bovine herpesvirus 1 (BoHV-1). The recombination of two BoHV-1 mutants lacking either glycoprotein C (gC−/gE+) or E (gC+/gE−) was investigated after inoculation of cattle by the natural route of infection. The results demonstrated that (i) recombination is a frequent event in vivo since recombinants (gC+/gE+and gC−/gE−) were detected in all coinoculated calves, (ii) relative proportions of progeny populations evolved during the excretion period toward a situation where two populations (gC+/gE+and gC−/gE+) predominated without fully outcompeting the presence of the two other detected populations (gC+/gE−and gC−/gE−), and (iii) after reactivation from latency, no gC+/gE−and gC−/gE−progeny viruses were detected, although gC+/gE−mutants, when inoculated alone, were detected after reactivation treatment. In view of these data, the importance of gE in the biology of BoHV-1 infection and the role of recombination in herpesvirus evolution are discussed.