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Biomedical subjects

E S Parker

Publications and source records attributed to E S Parker.

At least 19 recordsLinked to original sources
PubMed1996

Low level hyperbaric antagonism of diazepam's locomotor depressant and anticonvulsant properties in mice.

Exposure to 12 atmospheres absolute (12 ATA) helium oxygen gas (heliox) (low level hyperbaric exposure) antagonizes the behavioral effects of ethanol and n-propanol, but not morphine. These and other results indicate that the mechanism of the antagonism is direct (pharmacodynamic) and selective. Our study further investigates the selectivity of low level hyperbaric antagonism by testing its effectiveness against diazepam, a high affinity binding drug that acts via allosteric modulation of GABAA receptors. C57BL/6J mice received injections i.p. of vehicle or diazepam, and were then exposed to 1 ATA air, 1 ATA heliox or 12 ATA heliox. Exposure to 12 ATA heliox antagonized the locomotor depressant effect of 4 and 6 mg/kg, but not 8 mg/kg diazepam. Hyperbaric exposure also antagonized the anticonvulsant effect of 8 and 24 mg/kg, but not 4 mg/kg, diazepam vs. 300 mg/kg isoniazid. Exposure to 12 ATA heliox did not significantly affect blood concentrations of diazepam or its metabolite n-desmethyl diazepam. The pharmacological characteristics of the antagonism (direct, surmountable, rightward shift in diazepam's dose-response curve) closely matched those seen in previous studies for hyperbaric antagonism of ethanol. The results add to the evidence that low level hyperbaric exposure is a direct, mechanistic antagonist that selectively antagonizes drugs that act via perturbation or allosteric modulation of receptor function. Moreover, the results suggest that allosteric coupling pathways, which transduce binding events on ligand-gated ion channels, may represent initial sites of action for ethanol.

Animals↗
PubMed1995

University of Southern California Repeatable Episodic Memory Test.

The University of Southern California Repeatable Episodic Memory Test (USC-REMT) was developed to provide a brief assay of memory in clinical drug trials where the same subject is tested multiple times over days or weeks. Therefore, it had to be minimally affected by repeated testing. The test also provides a measure of subjective organization, a cognitive strategy that might be sensitive to frontal lobe dysfunction and HIV-related memory deficits. The USC-REMT has seven different lists, each composed of 15 semantically unrelated, high-frequency nouns. The words are presented in a different order on three study-test trials. After each study trial the subject recalls the words in any order. The test takes about 10 min to administer and score. The recall protocol can be scored for (a) global mnemonic efficiency, (b) primary and secondary memory, (c) subjective organization, (d) recall consistency and (e) recall as a function of serial position. We report initial data showing that the test is sensitive to memory decrements. Thirty-six HIV-1 seropositive men, at various stages of illness, recalled significantly fewer words and exhibited less subjective organization than 14 matched controls. The test had no significant practice effects over the first three administrations when separated by several days. The seven alternate lists are essentially equivalent. The USC-REMT appears to complement currently published verbal memory tasks.

Adult↗
PubMed1995

Low-level hyperbaric exposure antagonizes locomotor effects of ethanol and n-propanol but not morphine in C57BL mice.

Low-level hyperbaric exposure antagonizes a broad range of behavioral effects of ethanol in a direct, reversible, and competitive manner. This study investigates the selectivity of the antagonism across other drugs. C57BL/6 mice were injected with saline, ethanol, n-propanol, or morphine sulfate, and then were exposed to 1 atmosphere absolute (ATA) air, 1 ATA helium-oxygen gas mixture (heliox), or 12 ATA heliox. Locomotor activity was measured from 10 to 40 min following injection. N-propanol produced a dose-dependent depression of locomotor activity from 1.0 g/kg. Morphine produced a dose-dependent stimulation of locomotor activity at doses of 3.75-12.0 mg/kg. Exposure to 12 ATA heliox significantly antagonized the locomotor depressant effects of 1.0 g/kg n-propanol and 2.5 g/kg ethanol, without significantly affecting blood concentrations of these drugs measured at 40 min postinjection. Exposure to 12 ATA heliox did not significantly antagonize the locomotor-stimulating effects of the two morphine doses tested (3.75 and 7.5 mg/kg). These findings suggest that exposure to 12 ATA heliox antagonizes the behavioral effects of intoxicant-anesthetic drugs like ethanol and n-propanol, which are believed to act via perturbation or allosteric modulation of functional proteins, but does not antagonize the effects of drugs like morphine, which act via more direct mechanisms. This demonstration of selective antagonism adds important support for the hypothesis that low-level hyperbaric exposure is a direct mechanistic ethanol antagonist, with characteristics similar to a competitive pharmacological antagonist.

1-Propanol↗
PubMed1994

High false alarm rates on a vigilance task may indicate recreational drug use.

Neuropsychologists need more sensitive methods to detect and measure recreational drug use in both research and clinical settings. In a study comparing the sensitivity of information processing tasks and neuropsychological instruments to detect early HIV-related cognitive decrements, 18 of 129 subjects tested positive for recreational drugs. Sixteen of these 18 subjects had elevated false alarm rates on one of the information processing tasks, the vigilance task. Another 45 subjects who tested negative for recreational drugs also had elevated false alarm rates. Neuropsychological measures of premorbid functioning, attention, speed of information processing, and manual dexterity were lower in the high false alarm subjects than in the remaining 66 drug-negative, low false alarm subjects. These results suggest that a high false alarm rate may reflect long-standing cognitive disturbances and the effects of drug use. The vigilance task may be a sensitive and efficient screening tool for recreational drug use.

AIDS Dementia Complex↗
PubMed1991

Specifying the relationship between alcohol use and cognitive loss: the effects of frequency of consumption and psychological distress.

Previous research has found a relationship between increased quantity of alcohol usually consumed per drinking occasion and decreased sober cognitive performance. It has been suggested that the effects of quantity of alcohol consumed may be conditional upon the frequency of alcohol use and that decreased performance in social drinkers may be a consequence of psychological distress (i.e., anxiety and depression). An analysis of data from a representative sample of employed men and women in metropolitan Detroit indicates that the relation between quantity of alcohol consumed per occasion and abstraction performance is conditional upon the frequency of alcohol use but that the relationship cannot be accounted for by psychological distress.

Adult↗
PubMed1991

Results of extended peptide T administration in AIDS and ARC patients.

We report here the extended Phase I testing of d-ala-Peptide-T-amide (Peptide T) in open trial. The drug was given intravenously in doses ranging from 0.1 to 3.2 mg/kg/day to 14 acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) patients for 12 weeks. Following a 4-week off-drug period, the first 6 patients finishing the intravenous testing were continued on intranasal drug, 25 mg/day, for 8 weeks. Control subjects were tested on the same neuropsychologic tests, but did not receive drug. Minimal evidence of toxicity was found. Performance increments in cognitive and neuromotor function were observed in patients with moderate neuropsychologic impairment compared with controls. Changes in constitutional symptoms included weight gain averaging 2 kg and reported improved sense of well-being. The latter findings were independent of variation in cognitive and neuromotor function. Measures of immunologic function and antiviral activity did not change significantly during the study. These data provide a scientific rationale for Phase II testing of Peptide T in human immunodeficiency virus-1 (HIV-1) patients focusing on neuropsychiatric outcome.

AIDS-Related Complex↗
PubMed1988

An atypical neurocognitive profile in alcoholic fathers and their sons.

Prepubescent boys and their recovering alcoholic fathers exhibited an Atypical Neurocognitive Profile consisting of (1) a reduction in amplitude of the late positive complex (LPC) of the event-related potential (ERP) during a complex visual discrimination task, and (2) reduced visuoperceptual performance evidenced by significantly lower scores on the Object Assembly, Block Design and Picture Completion subtests of the WISC-R and the Embedded Figures Test. Low LPC amplitudes were significantly correlated with poorer visuoperceptual performance. This Atypical Neurocognitive Profile may represent a marker for alcoholism.

Adult↗
PubMed1987

Alcohol use and depression symptoms among employed men and women.

A representative sample of 1,367 employed men and women in Detroit responded to questions about drinking practices and symptoms of depression. After controlling for age, education, family income, marital status, medication use, fathers' drinking, and other variables, increased quantity of alcohol consumed per drinking occasion was associated with increased depression symptoms in the sober state among men and women. Depression symptoms may be one of a group of not fully identified drug after-effect disorders involving psychological functioning.

Adult↗
PubMed1985

The impact of fathers' drinking on cognitive loss among social drinkers.

This chapter examines cognitive loss in social drinkers. The question of concern is whether the relationship between increased levels of alcohol consumption and reduced sober cognitive performance is misspecified. In particular, does reduced abstraction performance in social drinkers result from parental heavy drinking rather than, as we have proposed, from social drinkers' current use of alcohol. Because offspring of alcoholics may be at high risk for cognitive deficits even in childhood, these deficits may be transmitted in alcoholic families. Thus, the relationship between increased drinking and sober cognitive loss might be eliminated if parental drinking is controlled. We report here, however, that the effects of current alcohol use on abstraction performance in a representative sample of employed men and women cannot be accounted for by fathers' drinking. Our findings indicate the need for further research on both the cognitive effects of parental drinking and current alcohol use.

Adult↗
PubMed1984

Sequence of alcohol presentation is important in the potentiation of long-term events.

Animal and human studies have demonstrated that, depending upon the sequence of alcohol presentation, long-term memory of events can either be enhanced or diminished. In the present study a similar phenomenon is demonstrated in the neuronal excitability of slices of hippocampus from guinea pig brains. Alcohol given after, but not before, 3 days of pentylenetetrazol (PTZ) administration to the intact animal produced kindling equivalent to 5 days of PTZ given by itself. This effect appears to be independent of the known withdrawal effects of alcohol and lasts for at least 14 days after the alcohol and PTZ administration have been discontinued.

Action Potentials↗
PubMed1984

Intact retention in acute alcohol amnesia.

Research on alcohol amnesia has focused on memory processes that are disrupted during intoxication. The present experiment examined the possibility that certain memory processes might be resistant to the amnesic effects of alcohol. Intoxicated and sober subjects studied a list of 29 words. They were then given one of three different retention tests: free recall, identification of degraded words based on the procedure used by Warrington and Weiskrantz (1970), and yes/no recognition. As expected, free recall was significantly impaired by alcohol intoxication. In contrast, in the identification test, intoxicated subjects benefited to the same degree as sober subjects from prior exposure to the items. The two groups did not differ in immediate recognition memory. The results of the free-recall and identification tasks are similar to findings with chronic amnesic patients and suggest that perceptual fluency is not affected by alcohol, whereas elaborative processes supporting recall are particularly sensitive to disruption during intoxication. The failure to find recognition impairment at the level of intoxication used in this study distinguishes temporary alcohol amnesia from chronic amnesia.

Adult↗
PubMed1984

Enkephalinergic-dopaminergic "reward" pathways: a critical substrate for the stimulatory, euphoric and memory-enhancing actions of alcohol--a hypothesis.

Recent evidence indicates that alcohol (ethanol) exerts specific effects on dopaminergic-enkephalinergic neuronal pathways which are involved with natural drive-induction and have also been implicated in reward and memory consolidation. It is proposed herein that the euphorigenic and "paradoxical" memory-enhancing effects of low doses of alcohol are related to its direct actions on this specific brain substrate.

Animals↗
PubMed1983

Alcohol and sober mood state in female social drinkers.

The goals of the present study were to measure the relationship between alcohol consumption in 93 female social drinkers and their cognitive functioning and mood in the sober state, and to investigate the possible causal effects of alcohol consumption on these variables. In the first test session, a limited relationship was seen between previous alcohol consumption and sober cognitive performance. A strong relationship was found between alcohol consumption and self-reported depression and anger in the sober state. Either a prolonged reduction in alcohol consumption or a prolonged maintenance of alcohol consumption was undertaken by random subsets of the original sample. In the second test session 6 weeks later, women who had been randomly selected to reduce their alcohol intake showed decreases in depression, anger, and mental confusion when they were sober, relative to women who maintained or increased their alcohol consumption over the same period of time. We found no changes in cognitive performance in these groups. We concluded that the simplest explanation of the findings is that relatively low levels of alcohol consumption produce substantial increases in depression and anger in the sober state in female social drinkers. The value of considering alcohol consumption as a continuous variable rather than a dichotomous variable with "safe" and "unsafe" zones was discussed.

Adult↗
PubMed1983

Alcohol use and cognitive loss among employed men and women.

A representative sample of 1,367 employed men and women in Detroit responded to questions about their drinking practices and then completed a cognitive test which measures abstraction abilities. Abstraction, tested while respondents were sober, decreased significantly as reported quantity of alcohol usually consumed per drinking occasion increased. (Am J Public Health 1983; 73:521-526.)

Adolescent↗
PubMed1982

Lesion-induced sprouting in the rat dentate gyrus is inhibited by repeated ethanol administration.

The effect of ethanol on hippocampal axonal sprouting was studied with a histochemical technique for identifying acetylcholinesterase. Unilateral lesion of the entorhinal cortex in adult rats produced an increase in the density of acetylcholinesterase staining in the outer molecular layer and a concomitant increase in the width of the pale-staining commissural-associational zone of the dentate gyrus. Other rats were given ethanol (11.3 +/- 0.45 grams per kilogram) for 2 weeks before and 9 days after receiving the lesion. Ethanol abolished the expansion of the commissural-associated zone. The effect of ethanol on sprouting axons suggests that it may inhibit recovery of function after brain injury.

Animals↗