Steroid-induced cataract: new perspective from in vitro and lens culture studies

Serum levels of carbohydrate-deficient transferrin (CDT) were measured in subjects of two independent studies using two different commercial kits. The kits measure CDT either as a percentage of total transferrin (AXIS %CDT, AXIS Biochemicals AS, Norway), or as the absolute amount (CDTect, Pharmacia, Sweden). In a population of males (mean age 41 years) consisting of alcoholics, heavy, moderate and non-drinkers, a strong correlation was found between AXIS %CDT and CDTect results (r = 0.92, n = 58, P < 0.001). Sensitivity and specificity in detecting chronic alcoholic drinking of over 60 g/day were 78 and 94% for the AXIS assay, and 83 and 88% for the CDTect assay, respectively. In a population from a birth cohort study, consisting of 21-year-old males and females with less excessive alcohol consumption, the correlation between AXIS %CDT and CDTect CDT was weaker but still statistically significant (r = 0.46, n = 212, P < 0.001). In this population, with specificities > 83% in detecting alcohol consumption levels of > or = 6 drinks per week, the sensitivities were low with both CDT assays (< 43% for > or = 6 drinks per week, and < 44% for > or = 16 drinks per week). These results suggest that (a) both assays are equally effective in detecting chronic drinking over 60 g/day in older alcoholic males, and (b) both assays are similarly ineffective in detecting less excessive regular drinking in young males and females.     

Characteristic magnetic resonance imaging entheseal changes of knee synovitis in spondylarthropathy

Although studies generally support a positive association between alcohol consumption and lung-cancer risk, the relationship between specific alcoholic beverages and lung-cancer risk has been inconsistent. We examined recent and past alcoholic beverage intake among 261 incident cases and 615 population controls enrolled in a lung-cancer case-control study of African Americans and Caucasians in Los Angeles County between 1991 and 1994. An in-person interview elicited information about past alcohol intake from ages 30 to 40 y, smoking, other lung-cancer risk factors, as well as recent intake of alcohol, and recent dietary intake. An association was observed between recent hard-liquor consumption and lung-cancer risk. The odds ratio (OR) for 1 or more drinks (1.5 oz or 0.051 mL) per day of hard liquor compared with infrequent liquor drinking (0-3 drinks per month), adjusted for smoking, the matching factors, saturated fat and other alcoholic beverages was 1.87 [95% confidence interval (CI) = 1.02-3.42]. No appreciable association was observed for total alcohol, whereas small inverse associations were observed for beer and wine, although confidence intervals were wide. An elevated lung-cancer risk was also observed for past liquor consumption (between ages 30 and 40 y). The adjusted OR for 1 or more drinks per day of liquor compared with infrequent drinkers was 1.83 (95% CI = 1. 06-3.15). Confounding of the association between alcohol and lung cancer by smoking was apparent. Although we devoted considerable efforts to adjusting for smoking in our analyses, residual confounding is still possible because smoking and alcohol are closely associated. In addition, case-control studies including this study should be viewed with caution because of possible selection bias. An increased risk of lung cancer might occur with moderate drinking of hard liquor but confirmation is required in larger studies.     

Screening for problem drinking: comparison of CAGE and AUDIT. Ambulatory Care Quality Improvement Project (ACQUIP). Alcohol Use Disorders Identification Test

OBJECTIVE: To compare self-administered versions of three questionnaires for detecting heavy and problem drinking: the CAGE, the Alcohol Use Disorders Identification Test (AUDIT), and an augmented version of the CAGE. DESIGN: Cross-sectional surveys. SETTING: Three Department of Veterans Affairs general medical clinics. PATIENTS: Random sample of consenting male outpatients who consumed at least 5 drinks over the past year ("drinkers"). Heavy drinkers were oversampled. MEASUREMENTS: An augmented version of the CAGE was included in a questionnaire mailed to all patients. The AUDIT was subsequently mailed to "drinkers." Comparison standards, based on the tri-level World Health Organization alcohol consumption interview and the Diagnostic Interview Schedule, included heavy drinking (> 14 drinks per week typically or > or = 5 drinks per day at least monthly) and active DSM-IIIR alcohol abuse or dependence (positive diagnosis and at least one alcohol-related symptom in the past year). Areas under receiver operating characteristic curves (AUROCs) were used to compare screening questionnaires. MAIN RESULTS: Of 393 eligible patients, 261 (66%) returned the AUDIT and completed interviews. For detection of active alcohol abuse or dependence, the CAGE augmented with three more questions (AUROC 0.871) performed better than either the CAGE alone or AUDIT (AUROCs 0.820 and 0.777, respectively). For identification of heavy-drinking patients, however, the AUDIT performed best (AUROC 0.870). To identify both heavy drinking and active alcohol abuse or dependence, the augmented CAGE and AUDIT both performed well, but the AUDIT was superior (AUROC 0.861). CONCLUSIONS: For identification of patients with heavy drinking or active alcohol abuse or dependence, the self-administered AUDIT was superior to the CAGE in this population.     

Screening trauma patients for alcoholism according to NIAAA guidelines with alcohol use disorders identification test questions

Drinking pattern criteria (drinking frequency and number of drinks per occasion) issued by the National Institute on Alcohol and Abuse and Alcoholism (NIAAA) to screen primary practice patients for alcohol problems were evaluated in 1216 injured patients treated in a regional trauma center. Vehicular crash victims predominated (50.2%, of whom 64.5% were drivers), followed by victims of violence (31.2%) and nonviolent-injury victims (18.5%). Alcohol Use Disorders Identification Test (AUDIT) questions #1 (drinking frequency) and #2 (drinks/day) were used to assess the patients for current alcohol dependence (CAD). AUDIT responses roughly approximating NIAAA guidelines (high threshold: drinks > or = 4 times/week, > or = 5 drinks/day) and those indicating less drinking (low threshold: drinks > or = 2-3 times/ week, > or = 3 drinks/day) were chosen. Comparisons were made relative to sensitivity and specificity of responses in detecting CAD. When low threshold responses were used for either question, sensitivity to detect CAD increased overall (#1 from 0.53 to 0.80, #2 from 0.62 to 0.88) as well as among the subgroups of patients, whereas specificity remained high or at acceptable levels overall (#1 from 0.95 to 0.82, #2 from 0.92 to 0.71) and among the subgroups of patients. Study findings suggest that, among injured drivers and other groups of trauma center patients, lesser amounts of drinking should be used as screening criteria for CAD than are used for the general population.     

Association between low contents of dopamine and serotonin in the nucleus accumbens and high alcohol preference

The contents of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were determined in the nucleus accumbens (ACB), frontal cortex (FR), anterior striatum (AST), and hippocampus (HIP) of adult male rats from the F2 generation of P x NP intercrosses. Rats were tested for their alcohol preference and were divided into two groups, depending on their alcohol intake. Rats in the high drinking group (n = 11) had ethanol intakes > 5g/kg/day, whereas the low drinking group (n = 15) had values < 1 g/kg/day. The content of DA in the ACB was lower (p < 0.001) in the high alcohol drinking group (46 +/- 2 pmol/mg tissue) than in the low intake rats (61 +/- 3 pmol/mg tissue). However, the contents of DOPAC and HVA in the ACB were similar for both groups. There were no differences between the two groups in the contents of DA in the FR or AST. The content of 5-HT in the ACB was lower (p < 0.05) in high alcohol drinking rats (6.3 +/- 0.3 pmol/mg tissue) than in the low intake group (7.0 +/- 0.2 pmol/mg tissue). The content of 5-HIAA in the ACB of the high intake rats was also lower than the level for the low drinking rats. There were no differences in the contents of 5-HT or 5-HIAA in the FR, HIP, and AST between the two groups. The results confirm a phenotypic association between abnormal DA and 5-HT systems projecting to the ACB and high alcohol drinking behavior in the P line of rats.     

Comparison of screening instruments for alcohol problems between black and white emergency room patients from two regions of the country

A number of brief screening instruments to identify alcohol dependence exist, but the validity of these instruments across ethnic groups or regions of the country is not well established. The sensitivity and specificity of a number of standard screening instruments (CAGE, brief MAST, AUDIT, TWEAK, and RAPS), as well as other measures (History of Trauma Scale, breathalyzer reading, self-reported drinking before the event, and consuming five or more drinks at a sitting at least monthly) are compared against ICD-10 and DSM-IV criteria for alcohol dependence between probability samples of Black and White emergency room patients in Santa Clara County, CA (n = 716) and in Jackson, MS (n = 1330). Variability in the sensitivity of screening instruments among current drinkers was found to be greater between samples for both Blacks and Whites, than for Blacks compared with Whites within the same sample. The AUDIT, TWEAK, and RAPS seemed to perform well by gender and injury status for both Blacks and Whites in the two samples, and no significant differences were found in the performance of these instruments across sample sites. To evaluate the influence of regional differences in alcohol dependence on differences found in the performance of screening instruments, using logistic regression with the simultaneous entry of demographic variables (age, gender, ethnicity, injury status, and site) and drinking variables (breathalyzer reading, self-reported drinking before the event, and drinking five or more drinks at a sitting at least monthly) to predict alcohol dependence in a merged sample of these patients (Jackson vs. Santa Clara) site was not found to be significant. Data suggest that, whereas region of the country may not be important in predicting alcohol dependence in emergency room populations, regional differences in the performance of screening instruments for alcohol dependence may exist, even when ethnicity is taken into account. Given distinct regional differences in drinking patterns and problems in the U.S., further research on commonly used screening instruments is needed to determine those screeners most efficient for identifying problem drinking.     

Sensitivity to change of the Roland-Morris Back Pain Questionnaire: part 2

OBJECTIVE: To determine whether blood pressure is reduced for at least 6 months with an intervention to lower alcohol intake in moderate to heavy drinkers with above optimal to slightly elevated diastolic blood pressure, and whether reduction of alcohol intake can be maintained for 2 years. DESIGN: A randomized controlled trial. METHODS: Six hundred forty-one outpatient veterans with an average intake of 3 or more alcoholic drinks per day in the 6 months before entry into the study and with diastolic blood pressure 80 to 99 mm Hg were randomly assigned to a cognitive-behavioral alcohol reduction intervention program or a control observation group for 15 to 24 months. The goal of the intervention was the lower of 2 or fewer drinks daily or a 50% reduction in intake. A subgroup with hypertension was defined as having a diastolic blood pressure of 90 to 99 mm Hg, or 80 to 99 mm Hg if recently taking medication for hypertension. RESULTS: Reduction in average weekly self-reported alcohol intake was significantly greater (P<.001) at every assessment from 3 to 24 months in the intervention group vs the control group: levels declined from 432 g/wk at baseline by 202 g/wk in the intervention group and from 445 g/wk by 78 g/wk in the control group in the first 6 months, with similar reductions after 24 months. The intervention group had a 1.2/0.7-mm Hg greater reduction in blood pressure than the control group (for each, P = .17 and P = .18) for the 6-month primary end point; for the hypertensive stratum the difference was 0.9/0.7 mm Hg (for each, P = .58 and P = .44). CONCLUSIONS: The 1.3 drinks per day average difference between changes in self-reported alcohol intake observed in this trial produced only small nonsignificant effects on blood pressure. The results from the Prevention and Treatment of Hypertension Study (PATHS) do not provide strong support for reducing alcohol consumption in nondependent moderate drinkers as a sole method for the prevention or treatment of hypertension.     

Mortality and light to moderate alcohol consumption after myocardial infarction

BACKGROUND: Although heavy alcohol consumption increases total mortality, light to moderate consumption decreases cardiovascular and all-cause mortality in apparently healthy people. Since data are sparse on the relation of light to moderate alcohol intake to mortality in patients with previous myocardial infarction, we did a prospective study of mortality in men. METHOD: Of 90,150 men in the Physicians' Health Study enrollment cohort who provided information on alcohol intake and who had no history of cancer, stroke, or liver disease, 5358 had a previous myocardial infarction. We estimated alcohol consumption by food-frequency questionnaire. FINDINGS: During a mean follow-up of 5 years, 920 men died. After adjustment for several potential confounders, moderate alcohol intake was associated with a significant decrease in total mortality (p=0.016). Compared with men who rarely or never drank alcohol, those who drank one to four drinks per month had a relative risk for total mortality of 0.85 (95% CI 0.69-1.05); for two to four drinks per week, the relative risk was 0.72 (0.58-0.89); for one drink per day 0.79 (0.64-9.96); and for two or more drinks per day 0.84 (0.55-1.26). INTERPRETATION: Men with previous myocardial infarction who consume small to moderate amounts of alcohol have a lower total mortality.     

Effect of kainate on the membrane conductance of hilar glial precursor cells recorded in the perforated-patch configuration

OBJECTIVE: To determine discontinuation effects of ipsapirone, a novel azapirone and partial 5-HTIA agonist that has anxiolytic effects clinically and has not caused dependence or withdrawal symptoms in animals, and to compare these effects with those of the benzodiazepine lorazepam, owing to concern about dependence or withdrawal symptoms following use of these drugs. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: Outpatient and inpatient treatment. PARTICIPANTS: Sixty-five healthy male volunteers who had experience with sedative-hypnotics or anxiolytics and did not meet DSM-III-R criteria for abuse or dependence. INTERVENTIONS: Participants were randomized to receive ipsapirone 15 mg per day (n = 17), ipsapirone 22.5 mg per day (n = 16), lorazepam 3 mg per day (n = 16), or placebo (n = 16) as outpatients for 36 days (treatment) followed by single-blind placebo as inpatients for 3 days and as outpatients for 6 days (withdrawal). OUTCOME MEASURES: Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Scale (HAM-D), Spielberger State Anxiety Scale, Sleep Quality Questionnaire, General Symptom Checklist, self-rated intoxication, Clinical Institute Withdrawal Assessment--Benzodiazepines (CIWA-Benzo), psychomotor testing and urine drug screen. RESULTS: Only 45 subjects completed the study; discontinuation rates did not significantly differ among treatment groups. At day 39, fewer and less severe symptoms (e.g., insomnia and fatigue) were found on the CIWA-Benzo scale after treatment with ipsapirone or placebo than after treatment with lorazepam (p < 0.05). Subjects reported longer sleep latency and poorer sleep quality after receiving lorazepam than after receiving ipsapirone or placebo. Scores on the HAM-D, Spielberger State Anxiety and HAM-A scales did not change from baseline. CONCLUSIONS: Withdrawal symptoms were detected after discontinuation of therapeutic doses of lorazepam. Significantly fewer symptoms were observed after withdrawal from anxiolytic doses of ipsapirone.     

Mechanical and chemical consequences of the residual stresses in plasma sprayed hydroxyapatite coatings

PURPOSE: To describe a preliminary investigation of a model of naltrexone therapy and counselling for use by primary care providers and evaluate its impact on drinking behaviors in a cohort of alcohol-dependent subjects. PATIENTS AND METHODS: The subjects enrolled in this study were 29 alcohol-dependent individuals. They were managed within a primary care treatment model located at a university-affiliated substance research program in New Haven, Connecticut. Subjects were assigned to a primary care provider for treatment of their alcohol dependence and were placed on naltrexone at a dose of 50 mg per day. They were seen for an initial "new patient" visit and 7 "brief" follow-up visits during the 10-week study. The primary outcomes for this study were completion of treatment, change in drinking behaviors from baseline, change in liver enzymes from baseline, provider ratings of improvement, and patient ratings of improvement and satisfaction with treatment. RESULTS: Of the 29 subjects: 21 (72%) completed treatment, and 10 (35%) relapsed to heavy drinking. All drinking behaviors improved significantly from baseline: percent of days abstinent increased from 36.6% to 88.8% (P < 0.0001), percent days abstinent from heavy drinking increased from 48.7% to 97.3% (P < 0.0001), and mean number of drinks per occasion decreased from 9.5 to 2.5 (P < 0.0001). The mean serum gamma glutamyl transferase (GGT) for the group decreased from 67.1 U/L to 45.3 U/L (P < 0.0001). CONCLUSIONS: In this preliminary investigation, treatment of alcohol dependence with our model of naltrexone and counselling by primary care providers appeared to be both feasible and effective.     

Characteristics of target-reaching in cats. III. Lifting and protraction with an obstacle in the movement path and after its removal

We have established a rat model that reflects the course of development of alcohol and opiate addiction. The present study with d-amphetamine aimed to define general principles in the development of an addiction. Male rats had a continuous free choice between d-amphetamine solutions (100, 200 and 400 mg/l) and water for 47 weeks. An initial intake of high doses of d-amphetamine during the first weeks of drug choice was followed by an individually stable pattern of drug consumption of moderate drug doses. During this period of controlled consumption (from week 10 to week 40), the voluntary intake of d-amphetamine depended on individual factors (dominant rats: 0.37+/-0.02 mg/kg per day, subordinate rats: 0.57+/-0.05 mg/kg per day) and environmental variables (group housing: 0.21+/-0.02 mg/kg per day, single housing: 0.41+/-0.03 mg/kg per day). Beginning with week 41, voluntary d-amphetamine consumption progressively increased (1.9+/-0.2 mg/kg per day in week 47), although the experimental conditions remained unchanged. Drug intake during a retest (free choice as before) after 6 months of drug deprivation revealed that the rats had persistently lost their control over drug intake and were no longer able to adjust drug taking to internal and external conditions. These addicted rats took very high drug doses, even when all d-amphetamine solutions but not water were adulterated with bitter tasting quinine (6.6+/-0.6 mg/kg per day; age-matched controls: 0.37+/-0.04 mg/kg per day). Forced intake of d-amphetamine for 47 weeks (7.1+/-0.3 mg/kg per day) via the drinking fluid caused physical dependence (hyperreactivity during withdrawal) but did not lead to drug addiction (voluntary intake in the retest with adulteration: 0.42+/-0.04 mg/kg per day). Both the temporal development and the prerequisites of psychostimulant addiction were in principle the same as for alcohol and opiates.     

A randomized trial of a brief primary-care based intervention for reducing at-risk drinking practices.

This randomized trial evaluated an intervention for reducing at-risk drinking practices in a sample of 307 patients. Eligible drinking patterns included chronic drinking (≥ 2 drinks per day in the past month), binge drinking (≥ 5 drinks per occasion at least twice in the past month), and drinking and driving (driving after ≥ 2 drinks in the past month). Members of the intervention group received a message from their physician during their regularly scheduled visit, a self-help manual, written personalized feedback, and up to 3 telephone counseling calls. Dropout was significantly higher in the intervention than control group. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evaluation of acetaldehyde-modified hemoglobin and other markers of chronic heavy alcohol use: effects of gender and hemoglobin concentration

The present study examined whether measurement of hemoglobin-acetaldehyde (HbA1-AcH) using an improved methodology may be useful as a biological marker of alcohol abuse. Red blood cell hemolysates of 182 patients consecutively admitted to the drug and alcohol treatment unit of our institution were analyzed for HbA1-AcH concentration using cation exchange HPLC. Mean HbA1-AcH of those who claimed to drink > or = 6 drinks/day [mean = 0.055 (% total hemoglobin), SD = 0.051] was significantly higher than the mean of those who drank < 6 drinks/day (mean = 0.026, SD = 0.0174). The greatest sum of sensitivity (67%) and specificity (77%) came with a cut-score of 0.030 area% of total hemoglobin. A cut-score of 0.080 produced a 100% specificity, but lowered the sensitivity to 20%. The Pearson product moment correlation (r) between HbA1-AcH and reported drinks per day was r = 0.30 (p < 0.001). There was no significant difference in the association of HbA1-AcH and reported drinking between males and females, and the small difference observed was shown to be entirely associated with differences in hemoglobin levels between the sexes. Cocaine use did not significantly alter the correlation between reported drinking and HbA1-AcH levels. Hemoglobin levels were shown to have a significant correlation with HbA1-AcH independent of drinking. HbA1-AcH was shown to have a better sensitivity and specificity than gamma-glutamyltransferase, ALT, AST, or mean corpuscular volume in this population. The results suggest that HbA1-AcH may be a useful marker to help detect alcohol abuse, especially in populations where other markers have been shown to fail.     

The effect of drinking intensity and frequency on serum carbohydrate-deficient transferrin and gamma-glutamyl transferase levels in outpatient alcoholics

Whereas heavy alcohol consumption is known to elevate serum carbohydrate-deficient transferrin (CDT) and gamma-glutamyl transferase (GGT) levels, the contribution of drinking pattern to these effects is not completely understood. We present data on 423 men and 146 women evaluated 1 year after treatment in a large-scale alcoholism treatment study (Project MATCH). Relationships between drinking frequency (number of days drinking), intensity (drinks per drinking day), and blood levels of CDT and GGT were analyzed by using response surface regression models and thin-plate spline-smoothing techniques. Both models indicated differences between CDT- and GGT-drinking pattern relationships in men and, also, a difference between men and women in CDT drinking-pattern relationships. For men, CDT levels appeared to respond primarily to frequency of drinking, whereas GGT was influenced primarily by drinking intensity. For women, both CDT and GGT were influenced more by drinks per drinking day (intensity) than by number of days drinking (frequency). The data confirm both the independent nature of these biological markers of alcohol consumption and gender differences in alcohol-induced CDT response reported previously.     

Aggressive treatment of childhood asthma with local steroids. Good or bad?

OBJECTIVES: Lipoprotein(a) consists of an LDL-particle attached to apolipoprotein(a), which is made by the liver. Diterpenes present in boiled coffee raise serum levels of LDL cholesterol and of the liver enzyme alanine aminotransferase in man. We investigated the association between intake of boiled coffee and serum levels of lipoprotein(a). DESIGN, SETTING AND SUBJECTS: Healthy Norwegians 40-42 years of age, who habitually consumed five or more cups of boiled coffee per day (n = 150) were compared with matched filter coffee consumers (n = 159) in a cross-sectional study, as part of the Norwegian National Health Screening in 1992. RESULTS: The median lipoprotein(a) level was 13.0 mg dL-1 (10th and 90th percentile: 2.5 and 75.0 mg dL-1, respectively) on boiled and 7.9 mg dL-1 (10th and 90th percentile: 1.9 and 62.5 mg dL-1, respectively) on filter coffee (P = 0.048). Means +/- SE were 25.8 +/- 2.4 mg dL-1 and 19.6 +/- 2.0 mg dL-1, respectively (P = 0.04). Although not statistically significant, subjects consuming nine or more cups of coffee per day had higher lipoprotein(a) levels than those drinking five to eight cups per day in both coffee groups. CONCLUSION: Chronic consumers of unfiltered, boiled coffee have higher serum levels of lipoprotein(a) than filter coffee drinkers.     

Drinking patterns as predictors of alcohol withdrawal reactions in DBA/2J mice

Individually housed DBA/2J mice were fed a liquid diet in which ethanol supplied 33% of the calories. The level of physical dependence that developed was estimated by scoring convulsions, elicited by handling the mice, after discontinuing the alcohol diet. The severity of the withdrawal reaction increased progressively with duration (5-12 days) of alcohol administration. A 2-day period on the diet produced no withdrawal reaction. Pretreatment of the mice with alcohol in their drinking water slightly increased the subsequent intake of the liquid diet. "Effective" alcohol intake was defined as uninterrupted alcohol consumption above 10 g/kg/day. Withdrawal scores correlated better with effective intake than with total intake under a variety of conditions. We interpret this to mean that brief interruptions in drinking (1 day) may allow the accrued physical dependence to disappear. On the basis of their effective alcohol intake, mice could be assigned to nondependent, moderately dependent or severely dependent groups for further study of the nature of physical dependence.     

Sensible drinking limits

A large number of prospective population studies from many countries have described a J- or U-shaped relation between alcohol intake and mortality. Both heavy drinkers and abstainers are at a higher risk of dying from all causes than individuals with light to moderate alcohol intake. This makes information to the public about sensible drinking limits more complex than, eg, that concerning smoking. The present paper aims at identifying upper thresholds for harmless alcohol intake. The review is mainly based on epidemiological evidence concerning somatic morbidity and mortality. It is concluded that the present Danish recommendations--14 drinks per week for women and 21 drinks per week for men--should be maintained. It is emphasized that these limits apply to adults who are at no risk of dependency and that they do not apply to pregnant women. Information about a potentially beneficial effect of a moderate alcohol intake should be reserved for individuals already at risk of coronary events.     

Alcohol and breast cancer in the Swiss Canton of Vaud

The relationship between alcoholic beverage drinking and the risk of breast cancer was considered using data from a case-control study of breast cancer conducted between 1990 and 1995 in the Swiss Canton of Vaud on 230 incident cases of breast cancer below age 75 years, linked with the Vaud Cancer Registry, and 507 controls admitted to the same network of hospitals for a wide spectrum of acute, non-neoplastic, non-hormone-related conditions. Overall, 70.4% of cases versus 57.4% of controls consumed alcohol, corresponding to a multivariate odds ratio (OR) of 1.5 (95% confidence interval (CI): 1.1-2.2). The ORs were 1.3 for < 1 drink per day, 1.8 for 1 to 2, 1.5 for 2 to 4, and 2.7 for > 4 drinks per day, and the trend in risk with dose was significant. The association was consistent for wine (OR = 2.0), beer (OR = 2.6) and spirits (OR = 2.0) and was apparently stronger in premenopausal women, whereas no noticeable interaction was observed with any of the hormonal or reproductive risk factors for breast cancer. The alcohol-related risk was unrelated to duration; the OR was 1.8 for women who started drinking below the age of 30 years and 1.4 for those starting at the age of > or = 30 years. Thus, the present study confirms that alcohol is a correlate of breast cancer risk in this European population, where alcohol drinking among women is common and relatively high. Assuming that this association reflects causality, in terms of attributable risk, alcohol could explain 25% (8-42%) of breast cancer cases.     

Effects of alcohol on sympathetic activity, hemodynamics, and chemoreflex sensitivity

Alcohol intake has been shown to worsen obstructive sleep apnea and increase nocturnal hypoxemia. The mechanisms of this action are unclear. Animal studies suggest that a reduction in chemoreflex sensitivity may be implicated. Using a double-blind, randomized, vehicle-controlled design, we tested the hypothesis that oral alcohol intake depresses chemoreflex sensitivity in humans. We examined the effects of oral alcohol intake (1.0 g/kg body wt) on blood pressure, heart rate, heart rate variability, muscle sympathetic nerve activity, forearm vascular resistance, and minute ventilation in 16 normal male subjects. Peripheral and central chemoreflex sensitivity were measured in response to hypoxia (n = 10) and hypercapnia (n = 6), respectively. Plasma alcohol increased from 0 to 23.2 +/- 1.5 mmol/L (107 +/- 7 mg/dL) at 60 minutes and 20.2 +/- 1 mmol/L (93 +/- 4 mg/dL) at 85 minutes after alcohol intake (P < .0001). Alcohol induced an increase in heart rate from 59 +/- 2 to 66 +/- 2 beats per minute (P < .01) and increased the ratio of low- to high-frequency variability of heart rate (P < .05). Although alcohol increased sympathetic nerve activity by up to 239 +/- 22% of baseline values (P < .01), forearm vascular resistance after alcohol was lower than that after vehicle (P < .05). Blood pressure did not increase compared with the vehicle session. Oxygen saturation during hypoxia after alcohol was 4 +/- 1% lower than it was during hypoxia after vehicle (P < .05) although arterial blood PO2 was unchanged. Alcohol did not affect the cardiovascular, sympathetic, or ventilatory responses to either hypoxia or hypercapnia. Acute increases in plasma alcohol increase heart rate and sympathetic nerve activity; blood pressure is not increased, probably because of vasodilator effects of alcohol. Alcohol does not alter chemoreflex responses to hypoxia or hypercapnia; thus, alterations in chemoreflex sensitivity are unlikely to explain the effects of alcohol on sleep apnea. Alcohol may reduce the affinity of hemoglobin for oxygen.     

A controlled trial of cue exposure treatment in alcohol dependence.

The clinical effectiveness of cue exposure (CE) treatment in alcohol dependence was evaluated in a controlled trial. 35 men who were detoxified and severely alcohol dependent received either CE or relaxation control (RC) treatment. CE Ss had 400 min exposure to the sight and smell of preferred drinks over 10 days in a laboratory setting. RC Ss spent identical time in the laboratory but had relaxation therapy and only 20 min exposure to alcohol cues. During 6-mo follow-up, personal interview was achieved with 91% of Ss. CE Ss had a more favorable outcome than the RC Ss in terms of latency (length of time) to relapse of heavy drinking (p?