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Biomedical subjects

C L Randall

Publications and source records attributed to C L Randall.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1993

Effects of prenatal ethanol exposure on later sensitivity to the low-dose stimulant actions of ethanol in mouse offspring: possible role of catecholamines.

The purpose of this study was to examine whether prenatal ethanol (EtOH) exposure alters later sensitivity to the low-dose stimulant effects of EtOH. Because the locomotor stimulant effects of EtOH are thought to be mediated, at least in part, by activation of brain monoamine systems, and because prenatal EtOH exposure has been shown to alter brain monoamine activity, it was hypothesized that prenatal EtOH exposure may alter sensitivity to the stimulant actions of EtOH. To test this hypothesis, sensitivity to the locomotor stimulant effects of various challenge doses of EtOH was examined in male and female offspring from prenatal alcohol (A), pair-fed (PF), and lab chow (LC) groups at different ages. In addition, to address the hypothesis further, sensitivity to the catecholamine synthesis inhibitor alpha-methyl-p-tyrosine (AMPT) was examined in these offspring, as well. Results indicated that male offspring prenatally exposed to EtOH exhibited reduced baseline activity and a blunted stimulant response to all challenge doses of EtOH (0.75-1.5 g/kg) in comparison with control offspring at 30 days of age, but these effects appeared to "normalize" at 70 days of age. Female EtOH-exposed offspring also exhibited a reduced baseline level of activity relative to control offspring, as well as a blunted stimulant response to the lowest challenge dose of EtOH (0.75 g/kg) at 30 days of age, and these effects persisted into adulthood. The stimulant response to higher doses of EtOH did not significantly differ among prenatal treatment groups in young or adult female offspring. However, because baseline activity was significantly lower in female EtOH-exposed offspring than control offspring, the stimulant response to these doses of EtOH (1.125 and 1.5 g/kg) was relatively greater than that for PF and LC offspring. Importantly, none of the differences in performance among the prenatal treatment groups could be attributed to an alteration in EtOH pharmacokinetics, because blood EtOH levels measured immediately following the 10-min test session were similar for all prenatal treatment groups across all of the EtOH test doses. Further, a similar response profile as that observed following EtOH challenge at 70 days of age was obtained following phenobarbital challenge (10-40 mg/kg). Finally, whereas AMPT (50-400 mg/kg) dose-dependently antagonized the stimulant effects of EtOH in all prenatal treatment groups, this effect of AMPT was significantly greater in mice prenatally exposed to EtOH in comparison with control offspring.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗
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↗
PubMed1988

PGE measurement in mouse embryos and uterine/embryo tissue.

Embryonic tissue of rodents and other species has been reported to produce prostaglandins (PG) of the E series during gestation. We attempted to establish the presence of PGE in C57BL/6J mouse embryos and peri-embryonic tissue as an initial step in examining the role of maternal ethanol treatment on PG production. Gestation day 10 embryos were found not to produce or degrade PGE. However, a tissue complex which included embryonic tissue, peri-embryonic membranes, placenta and uterus was capable of producing PGE from both endogenous and exogenous arachidonic acid. Furthermore, in vivo and in vitro aspirin was able to suppress PGE production from this tissue. It is concluded that gestation day 10 C57BL/6J mouse embryonic tissue, unlike that of rat, is not capable of measurable PGE production. However, uterine and peri-embryonic tissues, needed to support pregnancy, are capable of significant PGE production.

Analysis of Variance↗
PubMed1988

Role of alcohol-induced hypothermia in mediating the teratogenic effects of alcohol in C57BL/6J mice.

The purpose of this study was to determine the role of alcohol-induced maternal hypothermia in the teratogenic actions of alcohol. C57BL/6J mice were administered an acute dose of alcohol (5.8 g/kg orally) or isocaloric sucrose on day 10 of gestation. One half of each group was placed for 6 hr in an incubator set at 32 degrees C and the other half was housed in the incubator at room temperature (22 degrees C). As expected, acute prenatal alcohol exposure at this time of gestation was associated with decreased birth weight and an increase in limb and kidney malformations. The significant alcohol x environmental temperature interaction on these dependent variables indicated that the teratogenic insult was not attenuated, but was in fact even greater for the 32 degrees C/alcohol group. An absence of a main effect of environmental temperature indicated that the 32 degrees C environment, per se, was not teratogenic. Thus, maternal hypothermia is probably not an etiological factor in animal models of fetal alcohol syndrome. Moreover, antagonism of alcohol-induced maternal hypothermia exacerbates the teratogenic actions of alcohol observed at room temperature.

Abnormalities, Drug-Induced↗
PubMed1987

Effect of indomethacin on alcohol-induced morphological anomalies in mice.

The purpose of the present study was 1) to examine the effect of indomethacin (INDO), a prostaglandin synthesis inhibitor, on alcohol-induced growth and morphological impairment in C57BL/6J mice (Study 1) and 2) to determine if INDO crosses the placenta (Study 2). On day 10 of gestation, mice were injected (s.c.) acutely with either 0, 5, 10, or 20 mg/kg INDO, followed one hour later by alcohol (5.8 g/kg orally) or isocaloric sucrose. Fetuses were removed on day 19 of pregnancy, weighed, and examined for anomalous development. As expected, Study 1 demonstrated that maternal alcohol treatment decreased fetal weight and increased the number of fetuses with birth defects. INDO alone decreased fetal weight but did not affect morphologic development. More importantly, INDo antagonized alcohol-induced birth defects, but only at the highest dose. The results of Study 2 suggest that the relative ineffectiveness of INDO may be related to its inability to readily cross the placenta. Since high doses of INDO also caused maternal toxicity, the usefulness of this compound in future studies of this type was questioned.

Abnormalities, Drug-Induced↗