Estimating Alcohol Involvement in Trauma Patients: Search for a Surrogate

This study explores the potential for the development of a surrogate for alcohol-involved traumatic injury. It presents a bivariate probit analysis that simultaneously models likelihoods of patients being tested for blood alcohol content (BAC) and having positive BACs given testing using 17,356 adult trauma cases selected from the California Regional Trauma Registry. It concludes that patient and injury characteristics predict both testing and BAC, and that a weighting scheme may be profitably used to determine changes in levels of alcohol-involved trauma in populations over time in the absence of empirical measurement of BAC.     

The Role of Equine Herpesvirus Type 4 Glycoprotein K in Virus Replication

Equine herpesvirus 4 (EHV-4) is an important equine pathogen that causes respiratory tract disease among horses worldwide. Glycoprotein K (gK) homologues have been identified in several alphaherpesviruses as a major player in virus entry, replication, and spread. In the present study, EHV-4 gK-deletion mutant has been generated by using bacterial artificial chromosome technology and Red mutagenesis to investigate the role of gK in EHV-4 replication. Our findings reported here show that gK is essential for virus replication in vitro and that the gK-negative strain was not able to be reconstituted in equine cells. It is noteworthy that these findings agree with the previously published study describing gK deletion in other alphaherpesviruses.     

An Exploratory Analysis of Women and Men Within a Self-Help,Communal-Living Recovery Setting: A New Beginning in a New House

In the present exploratory study, women without children (n = 13) and women with children (n = 23) were compared to men (n = 35) on demographic and self-reported variables on entering a communal-living, self-help recovery program called Oxford House. Men were more often hospitalized for their addiction than either group of women, and men and women with children were older and had been previously hospitalized longer for their addiction than women without children. There were no significant differences among groups in terms of their codependency on others, and men felt a stronger sense of camaraderie with other residents than women with or without children. Men and women with children also tended to feel they shared more in the decisions within their house than did women without children. Further, with partial correlates (controlling for the number of children), women with children indicated that the greater their self-reported codependency, the less accepting they were of their children and the more depressed they were about their parenting abilities. Dysfunctional characteristics of the children also were related to negative characteristics in the children reported by their mothers. In short, men and women with and without children entering an Oxford House have similar profiles, yet women with children have additional stressors associated with parental responsibilities.     

Fine structure mapping of a gene-rich region of wheat carrying Ph1, a suppressor of crossing over between homoeologous chromosomes

The wheat gene-rich region (GRR) 5L0.5 contains many important genes, including Ph1, the principal regulator of chromosome pairing. Comparative marker analysis identified 32 genes for the GRR controlling important agronomic traits. Detailed characterization of this region was accomplished by first physically localizing 213 wheat group 5L-specific markers, using group 5 nulli-tetrasomics, three Ph1 gene deletion/insertion mutants, and nine terminal deletion lines with their breakpoints around the 5L0.5 region. The Ph1 gene was localized to a much smaller region within the GRR (Ph1 gene region). Of the 61 markers that mapped in the four subregions of the GRR, 9 mapped in the Ph1 gene region. High stringency sequence comparison (e < 1 x10(-25)) of 157 group 5L-specific wheat ESTs identified orthologs for 80% sequences in rice and 71% in Arabidopsis. Rice orthologs were present on all rice chromosomes, although most (34%) were on rice chromosome 9 (R9). No single collinear region was identified in Arabidopsis even for a smaller region, such as the Ph1 gene region. Seven of the nine Ph1 gene region markers mapped within a 450-kb region on R9 with the same gene order. Detailed domain/motif analysis of the 91 putative genes present in the 450-kb region identified 26 candidates for the Ph1 gene, including genes involved in chromatin reorganization, microtubule attachment, acetyltransferases, methyltransferases, DNA binding, and meiosis/anther specific proteins. Five of these genes shared common domains/motifs with the meiosis specific genes Zip1, Scp1, Cor1, RAD50, RAD51, and RAD57. Wheat and Arabidopsis homologs for these rice genes were identified.     

Unrelated donor bone marrow transplantation using a chemotherapy-only preparative regimen for adults with high-risk acute myelogenous leukemia

Limited data are available for adults undergoing unrelated donor (URD) BMT for AML using chemotherapy-only preparative regimens. Previous studies incorporated irradiation, included adults and children, and excluded secondary leukemia. Herein we report long-term outcomes for adults with poor-prognostic AML receiving a novel regimen of busulfan (16 mg/kg), cytarabine (8,000 mg/m(2)), and cyclophosphamide (120 mg/kg) (BAC), followed by URD BMT. From June 1995 through October 2001, 45 adults were enrolled. Adverse features included unfavorable cytogenetics (49%), secondary AML (47%), leukemia at transplant (42%), and extramedullary disease (16%). At time of BMT, 23 were in remission (12 CR1) while 22 had leukemia. Four (9%) died early. Acute and chronic GVHD rates were 44 and 67%, respectively. Seventeen (38%) were disease-free 52 months post-BMT; 13 were leukemia-free (eight CR1) at transplant. Eleven relapsed. Three-year DFS and OS were 42 and 46%, respectively. DFS and OS were longer, and relapses less, for those in CR at time of BMT. Secondary leukemia, cytogenetics, cell dose, and GVHD did not influence outcome. In poor-risk AML, BAC provided cytoreduction comparable to reported TBI-containing regimens, when administered for URD BMT. With decreasing treatment-related mortality, it is justified to proceed early to URD BMT for patients with poor prognostic features.     

A cross-national meta-analysis of alcohol and injury: data from the Emergency Room Collaborative Alcohol Analysis Project (ERCAAP)

Aims To examine the relationship of acute alcohol consumption with an injury compared to a non‐injury event in the emergency room across ERs in five countries. Design Meta‐analysis was used to evaluate the consistency and magnitude of the association of a positive blood alcohol concentration (BAC) at the time of arrival in the ER and self‐reported consumption within 6 hours prior to the event with admission to the ER for an injury compared to a non‐injury, and the extent to which contextual (socio‐cultural and organizational) variables explain effect sizes. Findings When controlling for age, gender and drinking five or more drinks on an occasion at least monthly, pooled effect size was significant and of a similar magnitude for both BAC and self‐reported consumption, with those positive on either measure over half as likely again to be admitted to the ER with an injury compared to a medical problem. Effect sizes were found to be homogeneous across ERs for BAC, but not for self‐report. Trauma center status and legal level of intoxication were positively predictive of self‐reported consumption effect size on injury. Conclusions These data suggest a moderate, but robust association of a positive BAC and self‐report with admission to the ER with an injury, and that contextual variables also appear to play a role in the alcohol–injury nexus.     

Cloning human herpes virus 6A genome into bacterial artificial chromosomes and study of DNA replication intermediates

Cloning of large viral genomes into bacterial artificial chromosomes (BACs) facilitates analyses of viral functions and molecular mutagenesis. Previous derivations of viral BACs involved laborious recombinations within infected cells. We describe a single-step production of viral BACs by direct cloning of unit length genomes, derived from circular or head-to-tail concatemeric DNA replication intermediates. The BAC cloning is independent of intracellular recombinations and DNA packaging constraints. We introduced the 160-kb human herpes virus 6A (HHV-6A) genome into BACs by digesting the viral DNA replicative intermediates with the Sfil enzyme that cleaves the viral genome in a single site. The recombinant BACs contained also the puromycin selection gene, GFP, and LoxP sites flanking the BAC sequences. The HHV-6A-BAC vectors were retained stably in puromycin selected 293T cells. In the presence of irradiated helper virus, supplying most likely proteins enhancing gene expression they expressed early and late genes in SupT1 T cells. The method is especially attractive for viruses that replicate inefficiently and for viruses propagated in suspension cells. We have used the fact that the BAC cloning “freezes” the viral DNA replication intermediates to analyze their structure. The results revealed that HHV-6A-BACs contained a single direct repeat (DR) rather than a DR-DR sequence, predicted to arise by circularization of parental genomes with a DR at each terminus. HHV-6A DNA molecules prepared from the infected cells also contained DNA molecules with a single DR. Such forms were not previously described for HHV-6 DNA.     

Mutation profile of <Emphasis Type="Italic">EGFR</Emphasis> gene detected by denaturing high-performance liquid chromatography in Japanese lung cancer patients

Purpose EGFR mutations in lung cancer increase sensitivity to an EGFR tyrosine kinase inhibitor, gefitinib. Mutation analysis of EGFR is essential for prediction of gefitinib response and avoidance of the coincidental severe side effects for the unresponsive population. The purpose of the present study is to apply DHPLC as a screening system of detection of EGFR mutations for large scaled population.Methods EGFR mutations were detected by both DHPLC procedure and direct sequencing using lung cancer tissue samples obtained from 97 patients (81 surgical specimens and 16 pleural effusions of non-resectable lung cancer patients).Results DHPLC analysis detected EGFR mutations in 5 h as opposed to 18 h by direct sequencing for ten samples, and it costs eightfold more expensive by direct sequencing than DHPLC. In addition, DHPLC analysis was sixfold more sensitive than sequencing analysis for detection of the point mutation of exon 21, L858R. Using this system, EGFR mutations in exons 18, 19 and 21 were found in 34 of 97 patients (36%). Thirteen of the 15 patients with exon 21 mutations (87%) were female non-smokers, who were diagnosed with adenocarcinomas with the feature of BAC. Eight of the 18 patients with exon 19 mutations (44%) were 7 male and 1 female current or former smokers, and BAC feature was observed in 61% (8/18).Conclusion DHPLC analysis for screening followed by sequencing analysis appears to be more sensitive and accurate, as well as easier and faster. In addition, these results suggest different mutagenesis and carcinogenesis pathways for mutations.     

Alcohol Consumption and Alcohol Pharmacokinetics: Interactions Within the Normal Population

We have analyzed the interrelationships between habitual alcohol consumption, peak blood alcohol concentration after a standard dose, and rate of alcohol metabolism in a group of 199 male and 213 female twins. Both peak concentration and rate of metabolism are strongly associated with alcohol consumption levels, even in the range of 0-10 g of alcohol/day. The peak concentration and rate of metabolism were strongly correlated in both men and women; this is not due to their common dependence on alcohol intake nor to experimental error. These results show that the threshold for effects of habitual consumption on alcohol pharmacokinetics is much lower than previously suspected, and that there are factors that reduce preabsorptive or first-pass metabolism but increase postabsorptive metabolism.     

Alcohol-Related Aggression in Males and Females: Effects of Blood Alcohol Concentration, Subjective Intoxication, Personality, and Provocation

This study tested the combined predictive ability of blood alcohol concentration (BAC), subjective intoxication, and aggressive personality traits on physical aggression in males and females in Highland Low-provocation conditions. Sixty intoxicated White social drinkers (30 males and 30 females) competed against a fictitious opponent on a modified version of the Taylor aggression paradigm in which subjects both received and delivered electric shocks to their opponents in provoking and nonprovoking conditions. Provocation conditions (High and Low) were defined by the intensity of the shocks the subjects received. Aggression was operationalized as the intensity of the shocks selected by the subjects. Results indicated that, for males in the High-provocation condition, aggressive personality traits, subjective intoxication, and BAC were effective predictors of physical aggression. However, in the Low-provocation condition, only aggressive personality traits and BAC predicted aggression. None of the variables were effective predictors of aggression for intoxicated females.     

The effectiveness of a 0.05 blood alcohol concentration (BAC) limit for driving in the United States

The National Transportation Safety Board recently recommended that states establish a per se blood alcohol concentration (BAC) limit of 0.05 or lower for all drivers who are not already required to adhere to lower BAC limits in a national effort to reduce alcohol‐impaired driving. There is strong evidence for adopting this recommendation. A comprehensive review of the literature on BAC limits was conducted. The research indicates that virtually all drivers are impaired regarding at least some driving performance measures at a 0.05 BAC. The risk of being involved in a crash increases significantly at 0.05 BAC and above. The relative risk of being killed in a single‐vehicle crash with BACs of 0.05–0.079 is 7–21 times higher than for drivers at 0.00 BAC. Lowering the BAC limit from 0.08 to 0.05 has been a proven effective countermeasure in numerous countries around the world. Most Americans do not believe a person should drive after having two or three drinks in 2 hours. It takes at least four drinks for the average 170‐pound male to exceed 0.05 BAC in 2 hours (three drinks for the 137‐pound female). Most industrialized nations have established a 0.05 BAC limit or lower for driving. Progress in reducing the proportion of drivers in fatal crashes with illegal BACs has stalled over the past 15 years. Lowering the BAC limit for driving from the current 0.08 to 0.05 has substantial potential to reduce the number of people who drink and drive in the United States and get involved in fatal crashes.     

Identifying drunkenness in the night-time economy

BACKGROUND: Prohibiting the sale of alcohol to intoxicated patrons by licensees and their staff requires definitions of drunkenness. AIMS: To assess the relationship between blood alcohol concentration (BAC) and indicators used in field sobriety tests putatively associated with intoxication. DESIGN, PARTICIPANTS, SETTING, MATERIAL AND METHODS: A random sample of 314 female and 579 male city centre drinkers. Surveyors scored respondents' and non-respondents' gait, eyes and speech for signs of drunkenness as well as their drunkenness on a 10-point Likert scale. Breath analysis was used to determine respondents' BAC. FINDINGS: Combinations of slurred speech, staggering gait and glazed eyes significantly predicted levels of BAC with a staggering gait indicating highest levels of intoxication. CONCLUSIONS: Subjective ratings of drunkenness by trained observers corresponded with BAC. Transition BACs denoting observable behaviour change associated with intoxication have been identified. Observations of gait, combined with assessment of slurred speech should be the basis of estimates of drunkenness.     

携带BARF1基因的重组巨细胞病毒的构建

目的 依据细菌人工染色体(Bacterial artificial chromosome,BAC)能够克隆大段DNA病毒的特点,通过galk为基础的同源重组,将EB病毒编码BARF1基因插入巨细胞病毒(cytomegalovirus,CMV),构建重组病毒。方法 PCR扩增带有巨细胞病毒UL57基因左右同源臂的galk及BARF1基因片段,经过电转化,进行同源重组,经含有galk培养基及脱galk培养基筛选,获得带有BARF1的巨细胞病毒细菌人工染色体克隆,提取质粒,转染到ARPE-19细胞,观察带有BARF1基因的巨细胞病毒对ARPE-19细胞的影响。结果 感染带有BARF1基因的巨细胞病毒的ARPE-19细胞形态由原来的长梭形变为变圆、肿胀、胞浆颗粒增多,并且细胞生长失去接触抑制,出现重叠生长现象。结论 建立了携带BARF1基因的重组巨细胞病毒;同时表明利用细菌人工染色体,可方便地对病毒基因组进行准确操作。     

Biphasic Effects of Alcohol on Heart Rate Are Influenced by Alcoholic Family History and Rate of Alcohol Ingestion

The present study investigated cardiac response to acute alcohol challenge along the blood alcohol concentration (BAC) curve in two groups of young adult nonalcoholic men with (MFH) and without (FH-) multigenerational family histories of alcoholism, matched for drinking history. BACs and resting heart rate measurements were recorded every 10 min for 3 hr after ingestion of a 1.0 ml/kg dose of 95% USP alcohol at two different rates: one of 20 min (slow drinking) and the other of 5 min (fast drinking). Several analyses of variance were performed for each of the dependent measures [BAC and heart rate change from baseline (HRCH)]. A significant risk × BAC phase interaction emerged from the HRCH analysis, indicating that the MFH group was characterized by a significantly greater increase in resting heart rate along the ascending limb of the BAC curve. A significant risk × BAC phase × rate interaction indicated that, when alcohol was consumed at a faster rate, men with multigenerational family histories of alcoholism demonstrated a greater HRCH, which persisted throughout the BAC curve.     

Alcohol and Heightened Aggression in Individual Mice

The objective of the current research was to study the large individual differences in alcohol effects on aggressive behavior under systematically varied conditions in experimental protocols with mice. Three experiments were conducted with outbred Swiss-Webster derived mice that identified those individuals whose aggressive behavior was reliably heightened by low acute alcohol doses. In all experimental protocols, low alcohol doses were orally administered to a “resident” male mouse that subsequently confronted an “intruder” opponent for 5 min while all salient elements of aggressive behavior and motor activities were quantified. In all three experiments, alcohol (1.0 g/kg) heightened aggressive behavior by at least two standard deviations of the individual's water vehicle control mean in 27% of the mice. In 64% of mice, no reliable change in aggressive behavior was detected after the identical alcohol treatment, and in 9% of the mice alcohol decreased aggressive behavior. Experiments differed in protocol indicating that these aggression-heightening effects were evident in resident mice that were either maintained at restricted or unlimited amounts of food, housed singly or in breeding pairs with a female partner, and conditioned to perform daily a food-reinforced task or remained undisturbed. The first experiment found the aggression-heightening effects to persist during weekly challenges for at least 2 months (n= 8 of 30). The second experiment showed these effects at intervals from 5 to 60 min after alcohol administration. Blood alcohol concentrations reached peak level within 5 to 10 min after oral administration in mice that had confronted an intruder. Those mice in whom alcohol heightened aggressive behavior (n= 21) did not differ from those that showed suppressed levels (n= 9) in terms of blood alcohol concentrations (79.6 vs. 82.4 mg%), suggesting that the intensity and frequency of aggressive behavior after alcohol were not directly dependent on the amount of alcohol in the circulation. The third experiment revealed that alcohol's (0.1 to 5.6 g/kg) effects on heightened aggressive behavior (n= 11) are dissociated from those on concurrently measured high- or low-rate operant performance as engendered by a multiple FR 30-FI 600 sec schedule of reinforcement. Current results indicate that this alcohol effect is relatively specific to aggressive behavior in individual animals, offering the opportunity for neuropharmacological and molecular characterization.     

Alcohol affects executive cognitive functioning differentially on the ascending versus descending limb of the blood alcohol concentration curve

BACKGROUND: Executive cognitive functioning (ECF), a construct that includes cognitive abilities such as planning, abstract reasoning, and the capacity to govern self-directed behavior, has been recently researched as an antecedent to many forms of psychopathology and has been implicated in alcohol-related aggression. This study was designed to examine whether differential ECF impairments can be noted on the ascending versus the descending limbs of the blood alcohol concentration curve. METHODS: Forty-one male university students participated in this study. Twenty-one subjects were given 1.32 ml of 95% alcohol per kilogram of body weight, mixed with orange juice, and the remaining 20 were given a placebo. Participants were randomly assigned to either an ascending or descending blood alcohol group and were tested on six tests of ECF on their assigned limb. Subjective mood data were also collected. RESULTS: Intoxicated participants on both limbs demonstrated ECF impairment; the descending-limb group showed greater impairment than their ascending-limb counterparts. Intoxicated subjects were significantly more anxious at baseline than placebo subjects. The introduction of this covariate nullified any significant differences in subjective mood found on either limb of the blood alcohol concentration curve, but ECF impairments remained robust. CONCLUSIONS: Our results support the conclusion that alcohol negatively affects cognitive performance and has a differential effect on the descending versus the ascending limb of the blood alcohol concentration curve. The latter finding may have important ramifications relating to the detrimental consequences of alcohol intoxication.