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Biomedical subjects

T L Wall

Publications and source records attributed to T L Wall.

At least 37 records · Page 2Linked to original sources

The firewater myth and response to alcohol in Mission Indians.

OBJECTIVE: This study aimed to assess empirically the intensity of reaction to alcohol in a group of Native Americans. METHOD: Forty healthy, nonalcoholic Mission Indian men between the ages of 18 and 25 years were tested before and after ingestion of placebo and 0.75 ml/kg of alcohol. Subjective (self-report of feelings) and objective (blood pressure, pulse rate, and plasma cortisol level) measures of intoxication were taken before ingestion of alcohol and placebo and at 15, 30, 60, 90, and 120 minutes after ingestion. Overall effects of alcohol were evaluated, and the responses of subjects with less than 50% Native American heritage (N = 19) were compared with the responses of subjects with at least 50% Native American heritage (N = 21). RESULTS: Alcohol did not produce any significant effects on any of the objective measures of intoxication; however, the subjects reported significant subjective effects of alcohol. Subjects with at least 50% Native American heritage reported less intense effects of alcohol than did those with less than 50% Native American heritage, despite equivalent blood alcohol concentrations. CONCLUSIONS: These results contradict the "firewater myth"--the theory that Native Americans are more sensitive to the effects of alcohol. Rather, the data indicate that Mission Indian men generally may be less sensitive to alcohol's effects, a physiological characteristic that has been shown to be associated with a greater risk for alcoholism in Caucasian populations. In addition, individuals with a greater percentage of Native American heritage may be less sensitive to the subjective effects of alcohol than individuals with a smaller percentage of Native American heritage.

Adolescent↗

Alcohol elimination in Native American Mission Indians: an investigation of interindividual variation.

The high prevalence of alcohol abuse and alcohol dependence among Native Americans may be mediated by unique environmental and genetic factors in this population. One factor that may influence the development of alcoholism is variability in alcohol metabolism. To determine factors that contribute to differences in alcohol elimination rates within a Native American population, this study evaluated healthy southern California Mission Indian men between the ages of 18 and 25 years. Each man drank a dose of alcohol, 0.56 g/kg of body weight as a 20% by volume solution, at approximately 9:00 AM after eating a low-fat breakfast and having fasted overnight. The drink was consumed within 7 min, and the concentrations of alcohol in blood were determined before and at 15, 30, 60, 90, 120, and 150 min after beverage ingestion. Rates of alcohol elimination were calculated from the pseudolinear slope of the blood alcohol versus time curve. The influences of estimated body water, recent drinking history, recent smoking history, polymorphism at the ADH2 and ADH3 loci, family history of alcoholism, and percentage Native American heritage on alcohol elimination rate were determined using multiple regression analyses. Estimated body water accounted for a significant proportion of the variance in alcohol elimination rate. There was also a nonsignificant trend for subjects with an ADH2*3 allele (n = 6) to have faster rates of alcohol elimination than those with ADH2*1 alleles only (n = 33). Given the high prevalence of alcoholism and alcohol-related health problems among Native Americans, the results from this study suggest that evaluation of alcohol metabolism and genotypes of the alcohol-metabolizing enzymes in Native American populations merits further study.

Adolescent↗

Alcohol expectancies in a Native American population.

Native Americans, as a group, have a high prevalence of alcohol abuse and alcohol dependence, although specific risk factors for alcoholism among this population have yet to be clearly identified. One set of factors that may contribute to the development of alcoholism are expectations of alcohol's effects. Previous research has shown that heavy drinkers and alcoholics have higher alcohol-related expectancies. Some studies have also shown an association between alcohol expectancies and a positive familial history of alcoholism. To examine factors that are related to expectations of alcohol's effects in a Native American population, this study evaluated healthy, nonalcoholic Mission Indian men between the ages of 18 and 25 years using the short form of the Alcohol Expectancy Questionnaire (AEQ). The influence of recent drinking history, family history of alcoholism, and degree of Native American heritage on alcohol-related expectancies was determined using regression analyses for the total AEQ score and for each of the six AEQ subscales. Recent drinking history accounted for a significant proportion of the variance in the total score, as well as scale I (global positive changes) and scale VI (arousal and power) of the AEQ. Degree of Native American heritage and family history of alcoholism did not account for a significant amount of variability in alcohol expectancies. These results suggest that, consistent with findings in other populations, alcohol expectancies are related to drinking patterns in Mission Indians. However, no association with two other potential risk factors were found in this sample of Native Americans.

Adolescent↗

Investigator-observed alcohol-induced flushing but not self-report of flushing is a valid predictor of ALDH2 genotype.

OBJECTIVE: This article presents data on the validity of using self-report of alcohol-induced flushing and actual investigator-observed flushing following alcohol challenge to predict ALDH2 genotype in Asian-American men. METHOD: Men between the ages of 21 and 25 years who were of Chinese, Japanese or Korean descent completed questionnaires about their drinking history and their alcohol-induced flushing history and associated symptoms. Fifty men selected for participation in the study were genotyped for alleles of ALDH2 and individually tested on two separate occasions following oral administration of placebo and 0.75 ml/kg (0.56 g/kg) alcohol. Facial flushing was assessed at baseline and at intervals over a 150-minute period after drinking using observational ratings. RESULTS: By comparing the results of ALDH2 genotype with investigator-observed flushing and with previous self-report of facial flushing, it was found that investigator-observed flushing is both a sensitive (100%) and specific (96%) predictor of ALDH2 genotype, whereas self-report of facial flushing is a sensitive (100%) but not a specific (68%) predictor of ALDH2 genotype. CONCLUSIONS: The results suggest that investigator-observed flushing provides a valid estimate of ALDH2 genotype, but that self-report of facial flushing is biased, giving a substantial overestimate. Due to an increase in error variance, studies that rely solely on self-report of flushing will more often lead to the conclusion that no association exists. This study supports the importance of using ALDH2 genotype, rather than self-report of flushing or ALDH2 phenotype, when examining factors associated with differences in drinking behavior, response to alcohol and risk for alcoholism or alcohol-related disease among Asians.

Adult↗

Psychiatric morbidity, illicit drug use and adherence to zidovudine (AZT) among injection drug users with HIV disease.

This study describes the relationship between the need for psychiatric consultation, illicit drug use, and zidovudine (AZT) adherence in HIV-infected injection drug users (IDUs) in methadone maintenance treatment (MMT). The treatment records of 57 IDUs in MMT who had been prescribed AZT between May and August of 1991 were reviewed. Those who required psychiatric consultation (P+, N = 46, 81%) were compared with those who did not require psychiatric consultation (P-, N = 11, 19%) on adherence to AZT treatment (using the mean corpuscular volume [MCV] as a biological marker), on recent illicit drug use, and on CD4 lymphocyte (T cell) count changes from the beginning to the end of AZT treatment. The P+ subjects were less likely than P- subjects to adhere to AZT treatment: fewer in the P+ group had an MCV outside of the normal range, and P+ subjects had a lower average monthly increase in MCV since the beginning of AZT treatment. Recent illicit drug use and CD4 lymphocyte count changes from the beginning to the end of AZT treatment did not show group differences. Psychiatric morbidity among HIV-infected IDUs in MMT is common, and may contribute to poor adherence to AZT treatment. Psychiatric screening and adherence-enhancing interventions should be targeted to IDUs entering drug treatment programs.

Adult↗

Adherence to zidovudine (AZT) among HIV-infected methadone patients: a pilot study of supervised therapy and dispensing compared to usual care.

Twenty-seven HIV-infected methadone maintenance patients who demonstrated problems adhering to zidovudine (AZT) were randomly assigned to a group that received eight weeks of weekday supervised therapy and dispensing of AZT or a group that received usual care of the clinic. Adherence was assessed by self-report, erythrocyte mean corpuscular volume (MCV), Medication Event Monitoring Systems (MEMS), and pill counts. Subjects in the intervention group demonstrated significantly higher MCV levels during the intervention period than usual care subjects, with similar but non-significant trends for the three other adherence measures. MEMS percent indicated significant group differences on weekdays, but not weekend days. There were no differences at a one-month follow-up. Results suggest supervised therapy and dispensing may be an effective strategy for improving AZT adherence, but only while provided. Further research is needed to establish the effects of larger and longer lasting interventions.

Adult↗

Acute effects of alcohol on P300 in Asians with different ALDH2 genotypes.

Asian men were genotyped for alleles of aldehyde dehydrogenase (ALDH2) and tested on two separate occasions following oral administration of placebo and 0.75 ml/kg alcohol. Sixty minutes after beverage ingestion, event-related potentials were elicited using an auditory oddball paradigm. Repeated measures ANOVA revealed that alcohol produced significant increases in P300 latency and significant decreases in P300 amplitude compared with placebo. Subjects with ALDH2*1/2*2 genotype (n = 14) demonstrated some significantly greater P300 effects after alcohol than subjects with ALDH2*1/2*1 genotype (n = 15), despite equivalent blood alcohol concentrations. These data suggest that neurocognitive functioning may be more impaired following alcohol in subjects with an ALDH2*2 allele. These findings further suggest that a genetically controlled factor (deficiency in ALDH enzyme activity) might contribute to a decreased likelihood of alcohol intake and protection from alcoholism, because of an enhanced sensitivity to alcohol.

Adult↗

Cortisol responses following placebo and alcohol in Asians with different ALDH2 genotypes.

Alcohol-induced flushing occurs in Asians who possess ALDH2*2 alleles. This study genotyped 30 Asian American men for ALDH2 and evaluated them on two separate occasions where they received in random order placebo and 0.75 ml/kg alcohol. Blood samples were drawn at baseline and 15, 30, 60, 90, 120 and 150 minutes after beverage administration for subsequent estimation of blood alcohol and plasma cortisol levels. Subjects with ALDH2*2 alleles demonstrated significantly higher cortisol levels after alcohol consumption than subjects with ALDH2*1/2*1 genotype, despite equivalent blood alcohol concentrations. One subject who was homozygous for ALDH2*2 had extraordinarily high cortisol levels at 90, 120 and 150 minutes after alcohol. These data are consistent with the hypothesis that Asians with ALDH2*2 alleles, who flush after drinking, experience more intense reactions to alcohol than nonflushing Asians with ALDH2*1/2*1 genotype.

Adult↗

Effects of acute alcohol administration on verbal and spatial learning.

The effects of alcohol and placebo on cognitive functioning in male, Asian-American college students were evaluated with a double-blind, placebo-controlled cross-over design using a multi-trial learning test in which verbal and spatial learning were simultaneously assessed. Verbal recall was impaired consistently across learning trials, while impairment of spatial recall was evident only on later learning trials. Recall of spatial information was influenced by order of presentation and amount of exposure time of items. Results do not support a theory that spatial learning is more impaired by alcohol than verbal learning, and thus do not lend support for the hypothesis that alcohol has a greater effect on right than left hemisphere functioning. Results provide evidence that alcohol increases susceptibility to interference effects.

Adult↗

Coupons attract high-risk untreated heroin users into detoxification.

This study examined the degree that the distribution of coupons brought drug users at risk of HIV infection into outpatient detoxification treatment. Demographic characteristics and outcome indicators were compared for patients recruited through coupon redemption (n = 238) versus other referral channels (n = 1129). Significantly more coupon subjects had no previous drug treatment, compared with non-coupon subjects (28% vs. 13%), had shared needles in the previous 30 days (39% vs. 31%) and more were ethnic minorities and men. Length of treatment stay and program completion rates did not differ between the groups. Within a year of the coupon project's end 43% of coupon subjects returned to the treatment program. Results suggest untreated heroin users will utilize drug treatment if more is available.

Adult↗

Corticotropin releasing factor (CRF): studies in alcohol preferring and non-preferring rats.

Electroencephalographic (EEG) responses to corticotropin releasing factor (CRF) as well as CRF concentrations in several brain regions were measured in two lines of rats which have been genetically selected for alcohol preferring (P) or non-preferring (NP) behaviors. Fifteen rats were implanted with chronic electrodes and EEG spectra were evaluated following intracerebroventricular (ICV) administration of CRF (0.15 nmol) or saline. P rats demonstrated a significantly increased EEG response to CRF in the theta frequency range (ANOVA: PREF x DRUG 4-6 Hz, P less than 0.03; 6-8 Hz, P less than 0.05) in frontal cortex. A significantly lower concentration of CRF was found in the P rats in hypothalamus (P less than 0.02), amygdala (P less than 0.003), prefrontal cortex (P less than 0.01), and cingulate cortex (P less than 0.02). The finding that P rats had an increased response to exogenously administered CRF, taken together with decreased CRF concentrations, suggests that CRF receptors may be up-regulated in these animals. Differences in the regulation of CRF neurons may contribute to the expression of behavioral preference for ethanol consumption in these rat lines.

Alcohol Drinking↗

Effects of dizocilpine (MK-801) and ethanol on the EEG and event-related potentials (ERPS) in rats.

Recent neurophysiological data have suggested an interaction of ethanol (EtOH) with the glutamate-NMDA receptor complex. For instance, low levels of alcohol have been found to inhibit the ion current, activated by NMDA in in vitro preparations. The present study extends these paradigms in order to evaluate the electrophysiological effects of ethanol and the nonspecific NMDA receptor antagonist, dizocilpine (MK-801) in awake, conscious rats. Twenty Wistar rats were stereotaxically implanted with electrodes, aimed at dorsal hippocampus, amygdala, thalamus and frontal cortex. Rats received the following drugs: saline (s.c.), 0.01 and 0.1 mg/kg MK-801 (s.c.); EtOH, 0.75 g/kg (i.p.); 0.75 kg EtOH plus 0.01 mg/kg MK-801; 0.75 g/kg EtOH plus 0.10 mg/kg MK-801. Five minutes of EEG was collected and event-related potentials (ERPs) recorded in response to an auditory "oddball" paradigm. Spectral analysis revealed that MK-801 (0.1 m/kg) produced significant increases in low frequency EEG components, at all sites (1-6 Hz) and decreases in higher frequencies (16-32 Hz). Whereas ethanol (0.75 g/kg) produced decreases in power in all frequency bands. The combined administration of EtOH and MK-801 produced some antagonistic effects on the EEG in the low frequency range. Evaluation of ERPs revealed that MK-801 (0.1 mg/kg) produced significant decreases in amplitude of the N1 and P2 components in the cortex, decreases in the P1 and N2 in the thalamus and a profound decrease in the P3 components in hippocampus and amygdala. Ethanol was also found to produce decreases in the N1 component in cortex. The administration of MK-801 and ethanol together did not produce significant interactions on ERPs. These studies suggest that antagonism of the NMDA receptor by MK-801 may produce some effects similar to those of ethanol, however, their combined administration did not produce synergistic effects within these dose ranges.

Amygdala↗

Subjective feelings of alcohol intoxication in Asians with genetic variations of ALDH2 alleles.

Asian-American men who possess ALDH2*2 alleles and who experience a facial flush after consuming alcohol were carefully matched on drinking history and demographic variables with nonflushing Asian males with only ALDH2*1 alleles. Each man was tested following placebo and a challenge dose of 0.75 ml/kg alcohol. Following alcohol, flushers reported experiencing significantly more positive feelings of intoxication than nonflushers, despite equivalent blood alcohol concentrations. These data suggest that Asians who flush after drinking, particularly those with ALDH2*1/2*2 genotype, have a more intense, although not necessarily a more negative, response to alcohol than comparable nonflushing Asians. This alcohol sensitivity reaction that many Asian flushers experience may contribute to their lower tendency to drink excessively, even though their response to alcohol is not predominantly negative.

Adult↗

Long latency event-related potentials in rats: effects of dopaminergic and serotonergic depletions.

The effects of serotonergic and dopaminergic depletions on event-related potentials (ERPs) generated by an auditory "oddball" paradigm were evaluated. Eighteen rats received either sham or six-hydroxydopamine (6-OHDA) lesions to the ventral tegmental area (VTA), and were subsequently implanted with electrodes in the frontal cortex, dorsal hippocampus (DHPC), and amygdala (AMYG). In these animals, a series of large amplitude potentials in the 10-200 ms latency range could be recorded from all the brain areas tested. In addition, late positivities (in the 300-400 ms range) were identified in DHPC and AMYG. 6-OHDA lesions to the VTA were found to produce a 30-46% reduction in dopamine, but did not significantly alter any of the ERP components. A second series of rats were implanted with electrodes in cortex and DHPC. These rats then received vehicle injections and subsequently injections of parachlorophenylalanine (PCPA). PCPA produced a 50% depletion of serotonin concomitant with significant reductions in the negative components in the 50-100 ms range recorded in hippocampus and cortex. These studies support a role for serotonin but not dopamine in the processing of passively presented auditory stimuli and further suggest that the rat may be a good model for the exploration of long latency ERPs.

Amygdala↗

Differential effects of ethanol on punished responding in the P and NP rats.

The effects of ethanol administration (0, 0.25, 0.5, 0.75 and 1.0 g/kg intraperitoneal) were examined in a conflict test in 24 alcohol-preferring (P)-rats, 17 alcohol-nonpreferring (NP)-rats, and 24 heterogeneous Wistar rats. The conflict test was a modified Geller-Seifter procedure employing an unpunished random interval 30-sec component and an incremental shock conflict component. Heterogeneous Wistar rats displayed significant increases in punished responding with doses of 0.5, 0.75, and 1.0 g/kg of ethanol. P-rats did not show a significant increase in punished responding until 0.75 g/kg ethanol. NP rats displayed significant increases in punished responding with all doses tested (0.25, 0.5, and 0.75 g/kg). There were no group differences in the effects of ethanol on unpunished responding. Thus NP-rats were more sensitive and P-rats were less sensitive to the anticonflict effects of ethanol than heterogeneous Wistar rats. The results suggest that the P and NP rats may show a profile of sensitivity to the anticonflict effects of ethanol similar to the sensitivity to the intoxicating effects of ethanol observed in family history positive and family history negative human subjects.

Alcoholism↗

Nucleus accumbens as a substrate for the aversive stimulus effects of opiate withdrawal.

Previous studies from our laboratory using methylnaloxonium, a hydrophilic antagonist, showed that opiate receptors in the region of the nucleus accumbens are important for the acute reinforcing effects of heroin in non-dependent rats. A similar increased sensitivity to the response disruptive effects of intracerebrally injected methylnaloxonium in opiate dependent rats was observed in a fixed-ratio (FR) baseline of operant behaviors. These results suggest that the same opiate receptors in the region of the nucleus accumbens important for the positive reinforcing stimulus properties of opiates may also be responsible for the response disruptive, aversive stimulus properties of opiate withdrawal. These results also suggest that the neural substrates of some aspects of dependence may be partly related to those of the reinforcing effects of opiates. In particular, it is hypothesized that "euphoria" and "dysphoria" induced by opiates may reflect opponent motivational processes operating at a cellular level within the nucleus accumbens.

Animals↗

EEG spectral characteristics following ethanol administration in young men.

The effects of consumption of low doses of ethanol (0.75 mg/kg) on spectral components of the EEG were investigated in 24 21-25-year-old males. A comparison of mean spectral power in 4 frequency bands (4-7 Hz, 7.5-9 Hz, 9-12 Hz, and 12-20 Hz) at 90 min post consumption revealed that ethanol, as opposed to placebo, significantly increased power in the two slower frequency bands, in both posterior and anterior leads. A reduction in the frequency at which power values peaked in the theta (4-7 Hz), fast alpha (9-12 Hz), and beta (12-20 Hz) frequency ranges was also seen following ethanol consumption. The ethanol induced lowering of peak power in the fast alpha range was observed in all 4 leads (F4-C4, P4-O2, F3-C3, and P3-O1), whereas the frequency changes in the theta and beta frequencies were only significant in a frontal lead. Ethanol was also noted to produce a decrease in the stability of the EEG in the fast alpha band as quantified by the coefficient of variation of power. Subjective response to ethanol was observed to vary depending on the subjects' pre-drug EEG pattern. Men with high amounts of fast alpha activity at baseline, in lead P4-O2, reported feeling less 'high' and less overall feelings of intoxication after ethanol than the men with lower amounts of pre-drug fast alpha waves. In addition, subjects were sorted into 'low' and 'moderate' drinkers depending on their quantity and frequency of drinking over the previous 6 month period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of alcohol on the EEG in Asian men with genetic variations of ALDH2.

Approximately 50% of Asians experience a facial flush following alcohol ingestion. These individuals have an inactive form of mitochondrial aldehyde dehydrogenase (ALDH) encoded by the ALDH2*2 allele. This study matched 15 flushing and 15 nonflushing Asian men on demographics and drinking histories. The 30 subjects were genotyped for ALDH2 and were evaluated both before and following placebo and 0.75 ml/kg alcohol. The two groups did not differ significantly on blood alcohol concentrations after drinking, but did differ in electroencephalographic (EEG) response on the falling phase of the blood alcohol curve. Nonflushing subjects displayed significant increases in slow-alpha EEG activity (7.5-9.0 Hz) at 90 and 150 min post-alcohol consumption, compared to flushing subjects who did not show characteristic increases in this frequency band at these timepoints. These data suggest flushers, those with at least one ALDH2*2 allele, have less of slow-alpha wave EEG response to alcohol than nonflushers with ALDH2*1/2*1 genotype.

Adult↗