Saccadic eye movements are associated with a family history of alcoholism at baseline and after exposure to alcohol

OBJECTIVE: To evaluate the influence of family history of alcoholism (FHA) on the response of saccadic eye movements to alcohol. METHOD: Saccadic performance was evaluated in 54 healthy adult subjects with a FHA (family history-positive) and 49 controls (family history-negative). Alcohol and placebo sessions were presented in counterbalanced order. Alcohol was administered intravenously to achieve and maintain a target breath alcohol concentration of 60 mg/100 ml (60%) for 160 min in each subject. During each session, saccadic eye movement testing was performed at baseline (before infusion of alcohol) and twice during the steady-state target breath alcohol concentration. The saccadic testing elicited visually guided saccades (VGS) and antisaccades (AS). Saccadic latency and velocity and the percentage of AS errors were quantified and analyzed using multivariate analysis of variance. RESULTS: The family history-positive and family history-negative groups showed an overall difference at baseline in AS and VGS latencies and velocities in the alcohol and placebo sessions ( p= 0.006). Alcohol delayed saccades such that AS and VGS latencies increased (p = 0.0001) and slowed the execution of saccades such that peak velocities decreased ( p = 0.0002). The percentage of AS errors decreased after alcohol administration, but no significant effect of alcohol (alcohol versus placebo session) was observed (p = 0.1). Latency of AS saccades demonstrated a significant overall FHA effect (p = 0.02) and a significant interaction between FHA and response to alcohol over time (p = 0.02). CONCLUSIONS: Differences in operational characteristics of the saccadic control system are associated with FHA in adult social drinkers, both at baseline and when the brain is exposed to ethanol at 60 mg/100 ml.     

Self-reported subjective perception of intoxication reflects family history of alcoholism when breath alcohol levels are constant

BACKGROUND: The premise of this study is that the increased familial risk for alcoholism is associated with genetic determinants of the response to alcohol, characterized by sensitivity and adaptation. Following a single administration, sensitivity is the initial response to alcohol, expressed as the change in dependent measures from baseline. Adaptation of dependent measures within a single exposure to alcohol can be expressed as acute tolerance (recovery of dependent measures toward baseline values) or sensitization (movement of dependent measure further away from baseline values). This study tested the hypothesis that family history-positive (FHP) subjects are more sensitive and more adaptive to alcohol compared with family history-negative (FHN) subjects. METHODS: The initial response and development of adaptation to alcohol were assessed by using self-reported subjective perceptions during a breath alcohol concentration (BrAC) clamp of 60 mg%. The Biphasic Alcohol Effects Scale, the Sensation Scale and a visual analog scale of intoxication were acquired at baseline, after the BrAC clamp was established, and after maintenance of the clamp for 105 min. RESULTS: FHP subjects were more sensitive to alcohol compared with FHNs, as evidenced by greater changes in feelings of intoxication when the BrAC clamp was initially achieved. While the clamp was maintained, the FHP subjects adapted to the effects of alcohol and their perceptions of intoxication became indistinguishable from those of the FHN subjects. The FHP subjects had developed acute tolerance to alcohol, whereas the FHN subjects did not. Other self-reported perceptions of alcohol's effects did not distinguish between the groups. CONCLUSIONS: A differential family history of alcoholism was reflected in self-reported subjective perceptions of intoxication when the brain's exposure to a specified concentration of alcohol was held constant (BrAC of 60 mg%). FHP subjects reported greater intoxication after alcohol and subsequently developed acute tolerance to alcohol compared with FHN subjects.     

Subjective perceptions associated with the ascending and descending slopes of breath alcohol exposure vary with recent drinking history

Background: The differentiator model predicts that individuals with a positive family history of alcoholism (FHA) or heavy alcohol consumers will feel more sensitive to the effects of alcohol on the ascending phase of the blood alcohol content while feeling less sedated on the descending phase. This study tested whether subjective perceptions are sensitive to the slope of breath alcohol concentration (BrAC) and whether that sensitivity is associated with an FHA and/or recent drinking history (RDH). Methods: Family‐history‐positive (FHP, n = 27) and family‐history‐negative (FHN, n = 27) young adult nondependent drinkers were infused intravenously with alcohol in 2 sessions separated by 1 week. After 20 minutes, one session had an ascending BrAC (+3.0 mg%/min), while the other session had a descending BrAC (?1 mg%/min). The BrAC for both sessions at this point was approximately 60 mg%, referred to as the crossover point. Subjective perceptions of intoxication, high, stimulated, and sedation were sampled frequently and then interpolated to the crossover point. Within‐subject differences between ascending and descending responses were examined for associations with FHA and/or RDH. Results: Recent moderate drinkers reported increased perceptions of feeling intoxicated (p < 0.023) and high (p < 0.023) on the ascending slope compared with the descending slope. In contrast, recent light drinkers felt more intoxicated and high on the descending slope. Conclusions: Subjective perceptions in young adult social drinkers depend on the slope of the BrAC when examined in association with RDH. These results support the differentiator model hypothesis concerning the ascending slope and suggest that moderate alcohol consumers could be at risk for increased alcohol consumption because they feel more intoxicated and high on the ascending slope. Subjects did not feel less sedated on the descending slope, contrary to the differentiator model but replicating several previous studies.     

A Preliminary Study of Acute Responses to Clamped Alcohol Concentration and Family History of Alcoholism

BACKGROUND: The clamping method of alcohol administration was combined with a battery of dependent measures of frontal lobe brain function, and a novel index of acute adaptation, in a preliminary study in order to explore the paradigm's sensitivity to a familial history of alcoholism (FHA). METHODS: Ten family history-positive (FHP) and 10 family history-negative (FHN) adult social drinkers of both genders underwent alcohol clamping. Twenty minutes after the start of an intravenous infusion of alcohol, the breath alcohol concentration was clamped at a target of 60+/-5 mg/dl for 150 min. Initial and adaptive responses to alcohol were assessed using scalar indices of change. One index assessed initial improvements or impairments in brain function after alcohol. The other index assessed acute adaptation (tolerance or sensitization) to alcohol while the brain's exposure to alcohol was held constant. The battery of dependent measures included subjective perceptions, neuropsychological tests, saccadic eye-movement tasks, and event-related potential (ERP) tasks. Effect sizes for FHA were estimated for 10 dependent variables that showed adequate baseline test-retest reliability (r>0.6). RESULTS: FHP subjects showed less intense initial responses to alcohol in subjective perceptions, but greater changes in the latency of volitional saccades and ERP P3 components than did the FHN controls. FHP subjects generally showed greater acute tolerance to alcohol than did controls, who showed more instances of acute sensitization at this moderate breath alcohol concentration. Effect sizes for FHA exceeded 0.4 in more than half of the indices. CONCLUSIONS: The BrAC clamping paradigm assesses initial and adaptive responses of a battery of behavioral and electrophysiological measures of frontal lobe function to ethanol that appear both reliable and sensitive to FHA.     

Intravenous Ethanol Infusions Can Mimic the Time Course of Breath Alcohol Concentrations Following Oral Alcohol Administration in Healthy Volunteers

Background: Our previous studies have used intravenous (IV) clamping methods to demonstrate that family history positive (FHP) subjects exhibit a greater initial response to alcohol than family history negative (FHN) subjects. These results differ from other studies of family history of alcoholism (FHA) influences, most of which have used an oral alcohol challenge, suggesting that the route of administration may influence both the response to alcohol and FHA‐related differences in response. To examine this possibility, one approach would be to directly compare responses following oral and IV alcohol administration in the same subjects. There is, however, a 3‐ to 4‐fold variance, between‐ and within‐subjects, in the breath alcohol concentrations (BrACs) following oral alcohol administration. Thus, our objective was to characterize the between‐subject variability in the time course of BrACs following oral alcohol administration in healthy volunteers and to develop an IV infusion method to mimic the BrAC‐time course attained following oral alcohol in the same subject. Methods: This was a 2‐session study in young adult, healthy, nondependent drinkers. In the first session, subjects ingested an oral dose of alcohol, based on total body water, to achieve a target peak BrAC of 80 mg%. In the second session, subjects received an IV infusion of ethanol designed to achieve the same BrAC time course as that achieved in the first session. The individualized infusion‐rate profile was precomputed using a physiologically‐based pharmacokinetic (PBPK) model for alcohol with model parameters adjusted to the individual’s physiology. The peak BrACs (C_max), times of peak BrAC (T_max), and the areas under the BrAC vs. time curve (AUC) were compared between sessions to assess how closely the BrAC exposure during the IV infusion session mimicked the exposure following oral alcohol. Results: The time course of BrACs following oral alcohol administration showed a high degree of between‐subject variability. Mean C_max, T_max, and AUC did not differ by gender, indicating that calculation of oral doses based on total body water results in comparable BrAC‐time courses, on average, for females and males. The IV infusion driven BrAC‐time profiles demonstrated good fidelity to the BrAC‐time curves resulting from oral alcohol: the mean %difference in C_max and AUC were both 11%, while the mean %difference for T_max was 27%. This degree of variability is less than half that seen across individuals following oral alcohol administration, which was substantial [coefficient of variation (%CV) ranging from 22 to 52%]. Conclusions: Despite the use of standardized doses and controlled experimental conditions, there was substantial between‐subject variability in the BrAC time course following oral administration of alcohol. The PBPK‐model‐based infusion method can mimic the BrACs attained with oral alcohol for individual subjects. This method provides a platform to evaluate effects attributable to the route of administration on the response to alcohol, as well as the influence of determinants such as family history of alcoholism on the alcohol response.     

Sleep following alcohol intoxication in healthy, young adults: effects of sex and family history of alcoholism

Background: This study evaluated sex and family history of alcoholism as moderators of subjective ratings of sleepiness/sleep quality and polysomnography (PSG) following alcohol intoxication in healthy, young adults. Methods: Ninety‐three healthy adults [mean age 24.4 ± 2.7 years, 59 women, 29 subjects with a positive family history of alcoholism (FH+)] were recruited. After screening PSG, participants consumed alcohol (sex/weight adjusted dosing) to intoxication [peak breath alcohol concentration (BrAC) of 0.11 ± 0.01 g% for men and women] or matching placebo between 20:30 and 22:00 hours. Sleep was monitored using PSG between 23:00 and 07:00 hours. Participants completed the Stanford Sleepiness Scale and Karolinska Sleepiness Scale at bedtime and on awakening and a validated post‐sleep questionnaire. Results: Following alcohol, total sleep time, sleep efficiency, nighttime awakenings, and wake after sleep onset were more disrupted in women than men, with no differences by family history status. Alcohol reduced sleep onset latency, sleep efficiency, and rapid eye movement sleep while increasing wakefulness and slow wave sleep across the entire night compared with placebo. Alcohol also generally increased sleep consolidation in the first half of the night, but decreased it during the second half. Sleepiness ratings were higher following alcohol, particularly in women at bedtime. Morning sleep quality ratings were lower following alcohol than placebo. Conclusions: Alcohol intoxication increases subjective sleepiness and disrupts sleep objectively more in healthy women than in men, with no differences evident by family history of alcoholism status. Evaluating moderators of alcohol effects on sleep may provide insight into the role of sleep in problem drinking.     

Development and pilot validation of computer-assisted self-infusion of ethanol (CASE): a new method to study alcohol self-administration in humans

Background:  Human alcohol self-administration studies employing oral intake are subject to high variability of the resulting blood alcohol concentrations because of idiosyncrasies of gastrointestinal absorption kinetics among subjects. We sought to improve the subjects' opportunity to control their brain alcohol exposure by computer-assisted i.v. self-administration.
Methods:  Instead of drinking, subjects could request increments of their arterial blood alcohol concentration (aBAC) of precisely 7.5 mg% at any time they wanted by pressing a button, provided their aBAC would not exceed 100 mg%. The latency between pushing the button and reaching the new aBAC peak was preset to be 2.5 minutes on the first day and was randomly changed to 1.5 or 3.5 minutes on days 2 and 3 in a crossover design. The necessary rate and amount of alcohol infusion was calculated by the software about once every second. Nine healthy social drinkers (4 females/5 males; mean age 25.0 ± 4.0 year) participated in 3 sessions each. Outcome measures were mean and maximum observed aBAC, and the number of alcohol requests.
Results:  Maximum aBAC was 76.5 ± 26.3 mg% on average over all experiments. When grouping days 2 and 3 according to latency (1.5 vs. 3.5 minutes), maximum aBAC and the number of requests in the session were significantly higher with the faster rise and all 3 outcome measures were significantly correlated between days. No such correlations were found between the first and either of the following days.
Conclusions:  These data suggest that CASE is practical and safe, and results in considerable alcohol exposure that can be manipulated with parameters chosen for the incremental exposure. Following 1 practice day, test–retest stability was good, suggesting a potential for use in scientific studies.     

Idiographically Determined Versus Standard Absorption Periods in Alcohol Administration Studies

Background: Effects of alcohol vary depending on blood alcohol level and limb. Some researchers use standard absorption periods (SAPs) to determine when postdrinking experimental protocols should begin. Others use an idiographically determined absorption period (IDAP) based on criterion breath alcohol concentration (BrAC). We investigated and compared the characteristics of each method. Methods: Sixty‐eight social drinkers (47% women) consumed a bolus dose of alcohol intended to raise BrAC to 0.08%. BrACs were recorded every 3 minutes until beginning to descend. Minutes to reach criterion BrAC (0.06%) and between‐subjects postdrinking BrAC variability were analyzed. Results: Mean time to reach 0.06% BrAC was 22.9 ± 14.6 minutes. Standard deviations in BrAC were 4 times greater using SAPs compared to IDAPs. Ten percent of participants’ BrAC readings were on the descending limb 30 minutes postdrinking, and 25% were descending at 45 minutes postdrinking. Conclusions: IDAPs result in less BrAC variability and may reduce experimental noise relative to SAPs. Experimental control in future alcohol administration studies may be enhanced by the use of IDAPs instead of SAPs.     

The relationship between cardiometabolic and hemostatic variables: influence of race

Elevated concentrations of hemostatic variables such as fibrinogen, plasma activator inhibitor 1 (PAI-1), and tissue plasminogen activator (t-PA)/PAI-1 complex have been implicated in the pathogenesis of arterial lesion progression and subsequent cardiovascular disease. In the present study, traditional cardiometabolic variables (CMV) associated with cardiovascular disease risk were examined in relation to hemostatic variables in a group of 36 White American (WA) and 30 African American (AA) overweight/obese women. There were 9 CMV significantly related to PAI-1 and/or the t-PA/PAI-1 ratio, but not fibrinogen. A significant race effect was found for 5 CMV in relation to fibrinogen and/or the t-PA/PAI-1 ratio, but not PAI-1. Significant race and high-density lipoprotein cholesterol interactions were found for fibrinogen (P = .021); and significant race and waist to hip ratio (P = .015), diastolic blood pressure (P = .013), and insulin (P = .037) interactions were found for PAI-1. No interactions were found for the t-PA/PAI-complex. Both PAI-1 and the t-PA/PAI-1 ratio are favored above fibrinogen in the diagnostic evaluation of health risk in both WA and AA women. Because of differences by race, independent consideration should be given in the clinical management of WA and AA women presenting with elevated CMV. Our findings indicated the t-PA/PAI-1 complex to be the most global indicator of health risk in both WA and AA overweight/obese women.     

The biphasic effects of alcohol: comparisons of subjective and objective measures of stimulation, sedation, and physical activity

BACKGROUND: Alcohol produces biphasic effects of both stimulation and sedation. Sensitivity to these effects may increase the risk for the development of alcoholism. Alcohol-induced changes in stimulation and sedation are commonly assessed with self-report questionnaires in human research and with physical activity monitoring in animal research. However, little is known about the effects of alcohol on physical activity or the relationship between physical activity and subjective self-report measures of stimulation and sedation following alcohol consumption in humans. METHODS: Thirty healthy men and women (n = 15 each) from 21 to 38 years old completed daily measurements of physical activity and self-reports of stimulation and sedation following alcohol or placebo consumption. Across each of the four experimental days, all participants consumed a placebo, 0.4, 0.6, or 0.8 g/kg dose of 95% alcohol in a counterbalanced order. Breath alcohol concentrations, physical activity levels, and self-reported stimulation and sedation were measured at baseline and on the ascending and descending limbs of the breath alcohol concentration (BrAC) curve. RESULTS: All alcohol doses increased physical activity, but these increases were time- and dose-dependent. Increases in physical activity lasted across both ascending and descending limbs of the BrAC curve. Following the 0.6 g/kg dose, both physical activity and self-reported stimulation increased during the ascending BrAC. Separate analyses of self-reported sedation scores indicated that alcohol consumption also increased sedation for the 0.6 and 0.8 g/kg doses. Physical activity was not significantly correlated with either self-reported stimulation or sedation at any time point. CONCLUSIONS: These findings suggest that assessments of subjectively measured stimulation and sedation and objectively measured physical activity each assess unique aspects of the effects of alcohol. Used simultaneously, these measures may be useful for examining underlying mechanisms of the effects of alcohol on behavior.     

Comparison of lung antioxidant levels in humans and laboratory animals

Basal lung concentrations of ascorbic acid (AA), nonprotein sulfhydryls (NPSH), and alpha-tocopherol (alpha-T) were determined in rabbits, guinea pigs, rats, hamsters, mice, domestic pigs and sheep, and in human lung samples obtained from cancer surgery patients. Significant differences were found among the laboratory animals: AA levels ranged from 25.6 mg% (mg/100 g wet weight) in hamsters to 41.7 mg% in mice, NPSH from 50.9 mg% in rats to 84.7 mg% in rabbits, and alpha-T from 1.01 mg% in hamsters to 2.74 mg% in rats. Porcine lung AA and NPSH concentrations approximated those of the laboratory animals and their alpha-T levels were the highest of all species studied. Sheep lung AA levels were comparable to those in the other species, although their NPSH and alpha-T levels appeared to be lower. Human lung concentrations of NPSH (5.2 mg%) and alpha-T (0.85 mg%) appeared low, whereas the mean AA concentration (22.1 mg%) was similar to that of laboratory animals. A partial correlation was found between AA and alpha-T levels and between NPSH and alpha-T levels in the 5 laboratory animal species.     

Functional Imaging of Cognitive Control During Acute Alcohol Intoxication

Background: The anterior cingulate and several other prefrontal and parietal brain regions are implicated in error processing and cognitive control. The effects of different doses of alcohol on activity within these brain regions during a functional magnetic resonance imaging (fMRI) task where errors are frequently committed have not been fully explored. Methods: This study examined the impact of a placebo [breath alcohol concentration (BrAC) = 0.00%], moderate (BrAC = 0.05%), and high (BrAC = 0.10%) doses of alcohol on brain hemodynamic activity during a functional MRI (fMRI) Go/No‐Go task in 38 healthy volunteers. Results: Alcohol increased reaction time and false alarm errors in a dose‐dependent manner. fMRI analyses showed alcohol decreased activity in anterior cingulate, lateral prefrontal cortex, insula, and parietal lobe regions during false alarm responses to No‐Go stimuli. Conclusions: These findings indicate that brain regions implicated in error processing are affected by alcohol and might provide a neural basis for alcohol’s effects on behavioral performance.     

Sexuality of Alcoholic Postmenopausal Women:Effects of Duration of Alcohol Abstinence

Little is known about the sexuality of alcoholic postmenopausal women, and even less is known about the influence of abstinence on self-assessed measures of sexual function. We now report findings in 60 postmenopausal women to whom a standardized questionnaire was administered. The responses provided information related to not only perceptions of sexuality, but also sexual behavior and performance. Women were categorized as alcohol abstinent (AA) for >l year (long AA, n = 33) or el year (short AA, n = 27). There were no differences between the groups in age, age at menarche, age at menopause, or age at onset of heavy drinking and alcohol dependence. The mean response rate to 12 sexuality-related questions was comparable in the long AA and short AA groups (83.8% and 85.6%, respectively), and reflected the prevalence of having a regular sexual partner (76% and 85%, respectively). There were statistical differences between the two groups with respect to sexual desire, arousability, and responsiveness during alcohol abstinence, but not during alcohol dependence. Further, there were significant differences with respect to measures of current sexuality:higher proportions of long AA women reported sex being important, as well as their sexual life and intercourse being satisfying. Taken together, these findings suggest that alcoholic postmenopausal women abstinent from alcohol for longer than 1 year report greater satisfaction with the sexual aspects of their lives than women abstinent for a shorter period of time.     

Person and environment predictors of blood alcohol concentrations: a multi-level study of college parties

Aims:  This study builds upon previous research by assessing the relationship of breath blood alcohol concentrations (BrAC) to environmental and individual characteristics.
Design:  We conducted a multi-level study of college parties. Our design included observational measures of party environments, a brief self-administered questionnaire, and the collection of breath samples from partygoers.
Setting:  Data were collected in private residences of students living in a neighborhood adjacent to a large public university located in the Southwestern United States.
Participants:  A total of 1,304 individuals attending 66 parties participated in the study.
Measures:  Observational measures of party characteristics were made by 2 trained research assistants at each party. Four to 5 trained interviewers administered a brief field survey to partygoers at each party. In addition, the trained interviewers collected breath samples using handheld breathalyzer devices.
Findings:  Hierarchical linear modeling analyses revealed significant variation at the party and individual levels. At the individual level, motivations to socialize were significantly associated with lower BrAC, while drinking games and providing the sample after 11:00  pm were associated with higher BrACs. At the party level, large parties were significantly associated with lower BrACs while reports of many intoxicated partygoers were associated with higher BrACs. Finally, we identified a significant gender by theme party interaction, indicating women had higher BrACs at theme parties relative to nontheme parties; however, BrACs for men were similar regardless of the type of party attended.
Conclusions:  Alcohol consumption among young adults in natural settings is a function of both person and environmental factors.     

The effects of binge drinking on college students' next‐day academic test‐taking performance and mood state

Aim To assess the effects of binge drinking on students' next‐day academic test‐taking performance. Design A placebo‐controlled cross‐over design with randomly assigned order of conditions. Participants were randomized to either alcoholic beverage [mean = 0.12 g% breath alcohol concentration (BrAC)] or placebo on the first night and then received the other beverage a week later. The next day, participants were assessed on test‐taking, neurocognitive performance and mood state. Participants A total of 196 college students (≥21 years) recruited from greater Boston. Setting The trial was conducted at the General Clinical Research Center at the Boston Medical Center. Measurements The Graduate Record Examinations© (GREs) and a quiz on a lecture presented the previous day measured test‐taking performance; the Neurobehavioral Evaluation System (NES3) and the Psychomotor Vigilance Test (PVT) measured neurocognitive performance; and the Profile of Mood States (POMS) measured mood. Findings Test‐taking performance was not affected on the morning after alcohol administration, but mood state and attention/reaction‐time were affected. Conclusion Drinking to a level of 0.12 g% BrAC does not affect next‐day test‐taking performance, but does affect some neurocognitive measures and mood state.     

Low HDL-Cholesterol with Normal Triglyceride Levels is the Most Common Lipid Pattern in West Africans and African Americans with Metabolic Syndrome: Implications for Cardiovascular Disease Prevention

BACKGROUND: Although designed to predict cardiovascular disease and type 2 diabetes mellitus, the Metabolic Syndrome (MetSyn) under-predicts these conditions in African-Americans (AA). Failure of MetSyn in AA is often attributed to their relative absence of hypertriglyceridemia. It is unknown if the African experience with MetSyn will be similar or different to that in AA. Focusing on the lipid profile, our goal was to determine in West Africans (WA) and AA the pattern of variables that leads to the diagnosis of the MetSyn. METHODS: Cross-sectional analysis of 1296 subjects (364 WA, 44% male, 932 AA, 46% male). WA were from urban centers in Nigeria and Ghana and enrolled in the Africa America Diabetes Mellitus Study. AA lived in Washington, DC and participated in the Howard University Family Study. RESULTS: The prevalence of MetSyn was different in WA women and men: 42% vs.19%, P<0.001, and in AA women and men: 25% vs.17%, P<0.01. The three variables that most often led to the diagnosis of MetSyn in WA and AA were: low HDL-C, central obesity and hypertension. Less than 40% of AA and less than 25% of WA with the MetSyn had hypertriglyceridemia. CONCLUSIONS: Elevated triglyceride levels were uncommon in both WA and AA with MetSyn. As the relative absence of hypertriglyceridemia is associated with a lack of efficacy of MetSyn in AA, caution is warranted in diagnosing MetSyn in WA, the ancestral population of AA. Prospective studies are necessary to determine if an ethnic-specific reformulation of the MetSyn scoring system for lipids might optimize risk identification in black populations.     

Alcohol affects eye movements essential for visually guided stepping

BACKGROUND: To understand how and why alcohol intoxication affects visually guided stepping, the eye movements and performance of 6 subjects (aged 22-35 years) were monitored as they progressed along a pathway of 18 irregularly placed stepping stones before and after consumption of an acute oral dose of alcohol. METHODS: Horizontal eye movements were measured with infrared reflectometry; footfall on or off target was monitored via copper fabric soles stuck to subjects' footwear. Breath alcohol concentration was monitored with an Alco-Sensor III breathalyzer. RESULTS: After alcohol loading, both locomotor and oculomotor deficits were evident. All subjects increased their step cycle duration-with prolonged stance, swing, and double support phases-and occasionally missed footfall targets. A large proportion of saccades made to fixate successive stepping stones were inaccurate and were accompanied by one or more corrective saccades. These problems with looking and stepping to footfall targets tended to occur together and were comparable to those seen previously in cerebellar patients undertaking the same task. CONCLUSIONS: The fact that healthy subjects acutely intoxicated by alcohol show symptoms of cerebellar dysfunction suggests that alcohol acutely and adversely affects the cerebellar contribution to performance of visually guided movements.     

高密度脂蛋白胆固醇与冠心病的关系（附600例临床分析）

本文通过６００例临床分析发现并确认：（１）冠心病心梗组的ＨＤＬ－ｃｈ平均浓度为３８．４０～４１．３１ｍｇ％，非冠心病组的ＨＤＬ－ｃｈ平均浓度为４９．５２～５２．７９ｍｇ％，前者明显低于后者；（２）ＨＤＬ－ｃｈ值都在３９ｍｇ％以下；（３）６０岁以上的人群中ＴＣ水平与冠心病之间可能没有肯定的关系，而ＴＣ／ＨＤＬ－ｃｈ比值升高较单纯ＴＣ的升高对诊断ＡＳ更有意义，该比值＞４：１较比值＜４：１时，冠心病的比例明显增加：（４）吸烟，肥胖者ＨＤＬ－ｃｈ值较不吸烟，体重正常者明显降低，提示吸烟，肥胖也是通过降低ＨＤＬ－ｃｈ促成ＡＳ病变的；（５）通过增加体育活动，减轻体重，停止吸烟，以及使用某些降脂药，均可提高血清ＨＤＬ－ｃｈ水平，这有利于预防和控制ＡＳ的发生和发展。     

Simultaneously recorded single-exhalation profiles of ethanol, water vapour and CO(2) in humans: impact of pharmacokinetic phases on ethanol airway exchange

The breath alcohol concentration (BrAC) standardized to the alveolar water vapour concentration has been shown to closely predict the arterial blood alcohol (ethanol) concentration (ABAC). However, a transient increase in the ABAC/BrAC ratio has been noted, when alcohol is absorbed from the gastrointestinal tract (absorption phase) and the ABAC rapidly rises. We analysed the plot of simultaneously recorded alcohol, water vapour and CO(2)?against exhaled volume (volumetric expirogram) for respiratory dead space volume (VD), cumulative gas output and phase III slope within one breath to evaluate whether changes in the BrAC profile could explain this variability. Eight healthy subjects performed exhalations through pre-heated non-restrictive mouthpieces and the concentrations were measured by infrared absorption. In the absorption phase, the respiratory VD of alcohol was transiently increased and the exhaled alcohol was displaced to the latter part of the expirogram. In the post-absorption phase, the respiratory VD for alcohol and water vapour was stable and always less than the respiratory VD for CO(2), indicating that the first part of the exhaled alcohol and water originated from the conducting airway. The position of the BrAC profile between water vapour and CO(2)?in the post-absorptive phase indicates an interaction within the conducting airway, probably including a deposition of alcohol onto the mucosa during exhalation. We conclude that the increase in the ABAC/BrAC ratio during the absorption phase of alcohol coincides with a transient increase in respiratory VD of alcohol and a delay in the appearance of alcohol in the exhaled air as the exhalation proceeds compared with the post-absorption phase.     

Measuring Liability for Substance Use Disorder among College Students: Implications for Screening and Early Intervention

Background: Heavy drinking and illicit drug use among college students has been a longstanding public health concern. Current methods to screen and identify college students at-risk for the development of substance use disorders (SUD) are somewhat limited. Objectives: This study aimed to cross-validate the work by Kirisci et al. (), who developed the Transmissible Liability Index (TLI), by deriving a set of items that would be potentially useful for characterizing SUD risk across multiple dimensions among college students. We examined: 1) variations in the TLI-College Version (TLI-CV) by race, sex, SES, religiosity, and family history of substance use problems; 2) the association between the TLI-CV and alcohol and/or marijuana dependence, both cross-sectionally and prospectively, by race and sex; and, 3) the sensitivity and specificity of the TLI-CV for identifying cases of marijuana and/or alcohol dependence. Methods: Data from an ongoing longitudinal study of college students (n = 1,253) was used to conduct item response theory (IRT) analyses; the resulting TLI-CV consisted of 33 items. Results: The TLI-CV was significantly associated with baseline dependence and significantly higher for non-dependent individuals who later became dependent during the subsequent three years of college. These associations were observed for both sexes, Whites, Blacks/African-Americans, Asians, and other racial minorities. The sensitivity and specificity were suboptimal. Conclusions and Scientific Significance: The TLI-CV advances prior research to identify college students at risk for SUD. This approach holds potential promise to identify and ultimately modify the trajectories of college students who may be at risk for the development of SUD.