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Biomedical subjects

C L Randall

Publications and source records attributed to C L Randall.

At least 19 recordsLinked to original sources
PubMed1995

Features of cocaine dependence with concurrent alcohol abuse.

In order to assess differences between cocaine dependence alone and cocaine dependence complicated by alcohol abuse, 34 subjects who met DSM-III-R criteria for alcohol abuse and cocaine dependence (COC-ETOH group) were compared with 39 subjects who met criteria for cocaine dependence only (COC-only group) with regard to demographics, substance use, and psychopathology. There were no differences between groups in age, race, employment or socio-economic status. The baseline depression and global severity scores in the COC-ETOH group were significantly higher than in the COC-only group. The COC-ETOH group was significantly more likely to experience a paranoid psychosis with cocaine use and significantly more likely to have abused additional substances in the month prior to study entry. The COC-ETOH group also attended significantly fewer medication management sessions during the 12-week trial. There were no differences between groups in the type or frequency of Axis 1 or Axis II disorders.

Adult↗
PubMed1995

Effect of ethanol on prostacyclin, thromboxane, and prostaglandin E production in human umbilical veins.

The purpose of this study was to determine the effects of ethanol on prostacyclin (PGI2), prostaglandin E (PGE), and thromboxane (TXA2) production in perfused human umbilical veins. PGI2, PGE, and TXA2 levels were measured from human umbilical veins perfused with either 25, 50, or 100 mM ethanol by radioimmunoassay of their stable metabolites. Alcohol content was measured by an enzymatic spectrophotometric assay. Data were analyzed by ANOVA and Fisher's Protected Least Significant Difference Test. Ethanol decreased PGI2 production in a concentration-dependent manner (p < 0.05). In a concentration of 25 mM, ethanol did not affect PGI2 production, whereas 50 mM decreased levels after 60 min of perfusion (p < 0.01). With 100 mM ethanol, PGI2 production was decreased after 15, 30, and 60 min of perfusion (ps < 0.05), and the TXA2/PGI2 ratio was significantly elevated at all time points (p < 0.01). Ethanol (100 mM) did not affect TXA2 or PGE production. Reduction of PGI2 levels and the increase in the TXA2/PGI2 ratio seen after ethanol perfusion in umbilical veins may cause vascular disruption in the umbilical-placental circulation. This may, in part, be a contributing mechanism to the teratogenic effects of ethanol.

Adult↗
PubMed1994

Issues in the definition and measurement of drinking outcomes in alcoholism treatment research.

This article reviews methodological and conceptual issues regarding the choice of drinking outcome measures in alcoholism treatment research. The following issues are discussed: Should drinking outcomes be conceptualized in terms of an underlying unitary disorder, or should provision be made for independent outcomes that cover a wide variety of dimensions? Which drinking outcomes are typically measured in treatment evaluation studies and how are they operationalized? What are the empirical associations among drinking outcome measures? If multiple outcomes are measured, which should be given primary importance? Over what period of time should treatment outcome be evaluated? What procedures can be used to detect, correct or prevent the response bias associated with verbal report methods? Because outcome measures need to fit the hypotheses and practical needs of a particular study, it is unlikely that complete standardization can be achieved across all studies. Nevertheless, given the importance of drinking outcomes and the need for economy, two primary dependent measures are recommended: (1) proportion of available drinking days abstinent; and (2) intensity of drinking, as defined by the total amount consumed (in ounces absolute alcohol) during the follow-up period divided by the number of actual drinking days. This article also proposes a strategy that may help to guide the selection of outcome measures in future research.

Alcoholism↗
PubMed1994

Multisite clinical trials in alcoholism treatment research: organizational, methodological and management issues.

Multisite clinical trials have two major advantages over single-site studies: the large sample size of multisite studies allows for adequate statistical power and better representativeness of the population being studied. However, they are more complex to implement than single-site studies. This article reviews previous multisite clinical trials of alcohol abuse and alcoholism, reasons for selecting a multisite design, management of such studies, and some statistical issues.

Alcoholism↗
PubMed1994

Issues in the development of subject recruitment strategies and eligibility criteria in multisite trials of matching.

Decision-making in selecting and recruiting subjects for treatment matching research is a complex process involving conceptual, methodological and practical considerations. In selecting clients, concerns arise about whether the criteria will produce a subject population that is (1) relevant to the dimensions associated with the treatment matching, (2) representative of persons typically seen in alcohol treatment settings and, for practical purposes, (3) able or willing to comply with the requirements of the study protocol. Also, in order to fulfill sampling requirements, it may be necessary to employ a variety of creative outreach methods. However, these recruitment mechanisms can pose additional logistical and methodological problems for the research. This article focuses on various issues arising in the selection and recruitment of subjects in matching research. Project MATCH serves to highlight issues related to client eligibility and recruitment and to discuss effective strategies for resolving these matters.

Adult↗
PubMed1992

Hypogastric arterial-vaginal fistula following multiple surgeries and pelvic radiotherapy.

A patient with recurrent sigmoid colon cancer developed an arterial-vaginal fistula after multiple surgeries and postoperative radiotherapy. Angiography revealed a fistula between the hypogastric artery and vaginal wall. Gelfoam and coil embolization controlled the hemorrhage and she recovered without incident. This case illustrates development of malignant fistula and intervention with embolization in a patient with multiple surgeries and postoperative irradiation in the pelvis.

Adenocarcinoma↗
PubMed1992

Aspirin pretreatment reduces ethanol withdrawal severity in a mouse model of binge drinking.

Nonsteroidal antiinflammatory drugs (NSAIDs) such as aspirin, ibuprofen, and indomethacin, which inhibit prostaglandin (PG) synthesis, have a pronounced effect on a broad range of ethanol (EtOH) actions. Given this, it is somewhat surprising that NSAID treatment has not been found to alter major signs of ethanol withdrawal. To date, the only effect found has been indirect, that is, NSAID treatment reduces the efficacy of PG precursor administration in the treatment of ethanol withdrawal via the inhibition of PG formation. However, in those studies reporting negative results NSAID administration was delayed until EtOH withdrawal. Studies demonstrating NSAID-related attenuation of other actions of EtOH have typically employed a pretreatment paradigm in which NSAIDs are administered prior to, not after, ethanol exposure. Thus, it may be that the point in the ethanol exposure/withdrawal episode at which NSAIDs are administered could be crucial in determining their effects of the ethanol withdrawal syndrome. To address this issue, we employed a multiple-exposure "binge drinking" model. On each of 6 treatment days, male BALB/c mice were injected subcutaneously with either acetylsalicylic acid (ASA, 150 mg/kg) or the buffer vehicle, followed 1 h later by either ethanol (4.0 g/kg) or saline (0.9%) by gavage. Ethanol withdrawal severity, as measured by handling-induced convulsions, was determined 2, 4, 6, 8, 10, 12, and 24 h after EtOH gavage. ASA pretreatment was found to significantly reduce handling-induced convulsions in ethanol-intubated animals. In fact, the attenuation was of such a magnitude that the ASA-pretreated ethanol group did not significantly differ in withdrawal severity from non-ethanol-exposed controls. This effect was not likely due to ASA-related alterations in ethanol pharmacokinetics. These findings have relevance for the understanding of the basic mechanisms underlying ethanol dependence, as well as the potential role of PGs in this phenomenon.

Alcoholism↗
PubMed1992

A placebo-controlled trial of buspirone in anxious inpatient alcoholics.

The present study is a double-blind control trial of buspirone versus placebo in highly anxious alcoholics who recently completed inpatient detoxification for alcoholism. Subjects met DSM-III-R criteria for generalized anxiety syndrome and/or other nonpanic forms of anxiety disorders and alcohol dependence. Male veterans aged 21 to 65 were randomized to 45 to 60 mg/day of buspirone (n = 33) or placebo (n = 34). Anxiety scores, as measured by the Hamilton Anxiety Scale and other anxiety measures, declined significantly for both groups, but there were no differential group differences throughout the 6-month treatment period. Survival analysis measuring time to study drop out, time to first drink, time to 5 consecutive drinking days, and time to first intoxication indicated no significant differences between groups. The number of standard drinks per drinking day for nonabstainers also did not differ between groups. In the present study anxious alcoholics taking buspirone did not receive any benefit over placebo on a number of anxiety and alcohol use measures.

Adult↗
PubMed1991

Aspirin dose-dependently reduces alcohol-induced birth defects and prostaglandin E levels in mice.

The purpose of the present study was threefold. The first purpose was to determine if aspirin (ASA) decreases alcohol-induced birth defects in mice in a dose-dependent fashion. The second purpose was to see if the antagonism of alcohol-induced birth defects afforded by ASA pretreatment was related to dose-dependent decreases in prostaglandin E (PGE) levels in uterine/embryo tissue. The third purpose was to determine if ASA pretreatment altered maternal blood alcohol level. In experiments 1 and 2, pregnant C57BL/6J mice were administered ASA (0, 18.75, 37.5, 75, 150, or 300 mg/kg) on gestation day 10. One hour following the subcutaneous injection of ASA, mice received alcohol (5.8 g/kg) or an isocaloric sucrose solution intragastrically. In experiment 1 the incidence of birth defects was assessed in fetuses delivered by caesarean section on gestation day 19. In experiment 2 uterine/embryo tissue samples were collected on gestation day 10 1 hr following alcohol intubation for subsequent PGE analysis. In experiment 3 blood samples were taken at five time points following alcohol intubation from separate groups of alcohol-treated pregnant mice pretreated with 150 mg/kg ASA or vehicle. The results from the three experiments indicated that 1) ASA dose-dependently reduced the frequency of alcohol-induced birth defects in fetuses examined at gestation day 19, (2) ASA decreased the levels of PGE in gestation day 10 uterine/embryo tissue in a similar dose-dependent fashion, and 3) ASA pretreatment did not significantly influence maternal blood alcohol levels. These results provide additional support for the hypothesis that PGs may play an important role in mediating the teratogenic actions of alcohol.

Abnormalities, Drug-Induced↗
PubMed1991

Psychosocial and psychopathology differences in hospitalized male and female cocaine abusers: a retrospective chart review.

While considerable amounts of psychological and pharmacological data have been collected on male substance abusers in public treatment facilities, relatively little information is available about the psychosocial characteristics of men in private treatment settings and of women presenting for substance abuse treatment. The present study reviewed the records of 100 male and female cocaine abusers admitted to a private substance abuse treatment program between 1987 and 1989. Patterns of cocaine use and levels of impairment were found to be similar for men and women, with male cocaine abusers more likely to abuse additional substances. Male cocaine abusers were employed more frequently than women and held higher status jobs despite equivalent levels of education. Female cocaine abusers were more likely to be diagnosed with concurrent psychiatric disorders and were more likely to report family histories of substance abuse. Both groups produced elevations on MMPI scales indicating depression, anxiety, paranoid features, and acting-out tendencies. These data suggest that while male and female cocaine abusers show similarities on some measures, there are significant gender differences that may have implications for both research and treatment.

Adult↗
PubMed1991

Increased severity of alcohol withdrawal in in-patient alcoholics with a co-existing anxiety diagnosis.

The purpose of this study was to determine whether alcoholics with a co-existing anxiety disorder (dual-diagnosed group) experienced different withdrawal symptomatology from alcoholics without an anxiety disorder (alcohol-only group). Symptoms of alcohol withdrawal were measured on admission to an in-patient treatment program and throughout treatment (days 0, 2, 7, 14 and 21) using the revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale. The dual-diagnosed group exhibited more severe alcohol withdrawal, as indicated by higher total CIWA-Ar scores, at all time points than the alcohol-only group. The possibility that anxiety disorders and alcohol withdrawal share a common neurochemical basis and that the CIWA-Ar scale may be useful as a screening instrument for anxiety disorders in alcoholics is discussed.

Adult↗
PubMed1991

Symptoms of anxiety in inpatient alcoholics with and without DSM-III-R anxiety diagnoses.

Self- and observer-rating scales were administered to alcohol-dependent inpatients during acute withdrawal and regularly for 3 weeks. Following a structured diagnostic interview (SCID) at the end of the 3rd week of hospitalization, subjects were divided into two groups: a dual-diagnosed group (alcohol dependence and anxiety disorder) and an alcohol-only group (no other current Axis I diagnosis). The results demonstrated that the dual-diagnosed subjects experienced higher anxiety levels during and after acute alcohol withdrawal. All rating scales (i.e., Sheehan Patient Rated Anxiety Scale, Spielberger State Anxiety Inventory, Zung Rating Scale for Anxiety, and Hamilton Rating Scale for Anxiety) were analyzed to obtain the best combination of sensitivity and specificity. Taken together, the results indicate that it may be possible to identify alcoholics who require additional psychiatric evaluation early in treatment. This would allow a treatment plan which could be used to address both psychiatric and substance abuse problems.

Adult↗
PubMed1991

Effect of ibuprofen on alcohol-induced teratogenesis in mice.

The purpose of the present study was to examine the effect of the prostaglandin synthetase inhibitor ibuprofen (IBU) on the teratogenic actions of alcohol. On day 10 of pregnancy, C57BL/6J mice were injected subcutaneously with 25 mg/kg IBU or vehicle control. One hour later, the mice were intubated with 5.8 g/kg alcohol or an isocaloric control solution. A group injected subcutaneously with 150 mg/kg aspirin, followed by 5.8 g/kg alcohol 1 hr later, served as a positive control. The results showed that maternal alcohol treatment resulted in significantly decreased fetal weight and an increased number of fetuses with limb and kidney defects. Implantation sites and prenatal mortality were not affected. IBU did not have any effect on these dependent variables. IBU statistically antagonized the teratogenic effects of alcohol on fetal weight and dysmorphology. These effects, however, were not as marked as in the Aspirin-Alcohol positive control group. These results are discussed in the context of clarifying the role of prostaglandins in the etiology of alcohol-induced birth defects.

Abnormalities, Drug-Induced↗
PubMed1990

Ethanol increases PGE and thromboxane production in mouse pregnant uterine tissue.

The teratogenic effect of ethanol in the C57BL/6J mouse can be attenuated by pretreatment with aspirin (ASA). One prominent effect of ASA is to inhibit prostaglandin (PGE) and thromboxane (TXB2) production. We examined the effect of in vivo ethanol exposure on PGE and TXB2 production in a uterine-embryo tissue sample of C57BL/6J mice either before or after in vivo ASA pretreatment on day 10 of gestation. Ethanol increased both PGE and TXB2 production by approximately 20%. ASA caused a marked reduction of PGE and TXB2 in both control and ethanol groups by approximately 80-90%. The mouse strain, gestation time, and study parameters used in this study were the same as in the previously reported ASA attenuation of the teratogenic effect of ethanol. Therefore, the present data add additional support to the hypothesis that prostaglandin and/or thromboxane production may be involved in at least some aspects of fetal alcohol syndrome.

Analysis of Variance↗
PubMed1990

Perspectives on the pathophysiology of fetal alcohol syndrome.

Fetal alcohol syndrome (FAS) is a major known cause of fetal malformations and mental retardation. Prevention/intervention of FAS can only be achieved with identification of the mechanisms by which alcohol induces birth defects. The purpose of this paper is to discuss the data on possible mechanisms of FAS, and to give a number of suggestions for future research areas.

Acetaldehyde↗
PubMed1989

Effects of prenatal ethanol exposure in C57BL mice on locomotor activity and passive avoidance behavior.

The purpose of this study was to examine the long-term behavioral effects of prenatal ethanol exposure in C57BL mice. Pregnant mice received free access to a liquid diet containing 25% ethanol-derived calories (EDC) from gestation days 6 to 18. Control animals were pair-fed an isocaloric 0% EDC diet during the same period of time. An additional control group was included that was maintained on standard lab chow and water throughout pregnancy. At 30 days of age, female offspring were tested for spontaneous locomotor activity in an open field under two lighting conditions (dim or bright illumination). Male offspring were tested in a passive avoidance task at 25 days of age. The activity results demonstrated that the 25% EDC female progeny were more active than controls. This hyperactivity was observed under both lighting conditions, despite the fact that all groups evidenced suppressed activity when tested under bright lights. With regard to passive avoidance behavior, male EtOH-exposed offspring required a greater number of trials to reach criterion than controls. Additionally, they exhibited shorter latencies to enter the shock-associated chamber after receiving a single shock. Taken together, these results confirm our previous findings and demonstrate that C57BL mice are sensitive to both the deleterious behavioral and morphological consequences of prenatal ethanol exposure.

Animals↗