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Biomedical subjects

S T Higgins

Publications and source records attributed to S T Higgins.

At least 19 recordsLinked to original sources

Psychiatric symptom severity in cocaine-dependent outpatients: demographics, drug use characteristics and treatment outcome.

Psychiatric symptom severity and associated characteristics were assessed in 185 individuals seeking outpatient treatment for cocaine dependence. The sample was divided into groups of low, medium and high psychiatric symptom severity based on Addiction Severity Index psychiatric composite scores. Patients with high symptom severity reported poorer pre-treatment functioning and more adverse consequences of cocaine use than the lower severity groups. Relationships between psychiatric severity and treatment outcome variables were assessed in a subset of 123 patients who received one of three 24-week psychosocial treatments for cocaine abuse: (i) behavioral treatment with a voucher-based incentive program; (ii) the same behavioral treatment without vouchers; (iii) or drug abuse counseling. Psychiatric symptom severity failed to influence treatment outcome with any of these treatments. Thus, in this study the authors found no evidence to indicate that high psychiatric severity predicts poor response to psychosocial treatment for cocaine abuse.

Adult

Alternate-day buprenorphine dosing is preferred to daily dosing by opioid-dependent humans.

Alternate-day buprenorphine dosing was compared to daily dosing in opioid-dependent outpatients and choice of alternate-day versus daily dosing was assessed. Four dosing schedules were presented in random order under blind and open dosing conditions. Subjects received two exposures to each dosing schedule. During daily dosing, subjects received maintenance doses every 24 h. During blind alternate-day dosing, subjects received double maintenance doses every 48 h; placebo was interposed on intervening days. During open alternate-day dosing, subjects received twice their maintenance dose on Monday, Wednesday and Friday and maintenance doses on Sunday. After completing two exposures to each dosing schedule, subjects chose either daily or alternate-day schedules each week for 1 month. Study participation was contingent on daily attendance and opioid abstinence. Ten subjects were exposed to the four conditions once. Seven subjects repeated these conditions and participated in the choice phase. The effects of daily versus alternate-day dosing were not influenced by blind or open dosing conditions. Subjects' ratings of withdrawal, "sick" and sedation were lower during daily than during alternate-day dosing, but the difference between treatments was small. Nonetheless, subjects still chose alternate-day dosing on 96% of occasions, suggesting that the subject-rated differences between dosing schedules were not influential. These results extend prior findings to open-dosing conditions, and replicate the safety and acceptability of alternate-day buprenorphine treatment. Choice of alternate-day buprenorphine administration underscores the procedure's clinical utility and potential use as a positive reinforcer to enhance opioid treatment.

Adult

Use of monetary reinforcement to reduce the cigarette smoking of persons with schizophrenia: a feasibility study.

The feasibility of using monetary reinforcement to promote abstinence from substance use in adult individuals with schizophrenia was addressed. Cigarette smoking was studied as an exemplar of drug use in 11 individuals with schizophrenia by use of a within-subject experimental design. The study duration was 3 weeks, with weeks 1 and 3 serving as baseline conditions and week 2 serving as the intervention condition; in the latter, patients could earn money by abstaining from cigarette smoking. Abstinence was significantly greater during the intervention condition than during the baseline conditions. These results illustrate the potential sensitivity of drug use in this population to reinforcement contingencies, suggesting that contingency-management interventions are a feasible option for treating the substance abuse of individuals with schizophrenia.

Adult

The influence of alternative reinforcers on cocaine use and abuse: a brief review.

This report reviews experimental studies conducted with nonhuman and human subjects demonstrating that: a) cocaine's abuse liability is, in part, a function of its positive reinforcing effects, b) cocaine use is operant behavior, c) the degree of behavioral control that cocaine exerts as a reinforcer is malleable and dependent on environmental context, and d) increasing the availability of alternative, nondrug reinforcers can significantly disrupt the acquisition and maintenance of cocaine use and abuse. Implications of these observations for effective prevention and treatment of cocaine abuse are discussed.

Animals

Effects of adding behavioral treatment to opioid detoxification with buprenorphine.

This trial assessed whether behavioral treatment improves outcome during a 26-week outpatient opioid detoxification. Thirty-nine opioid-dependent adults were assigned randomly to a buprenorphine dose-taper combined with either behavioral or standard treatment. Behavioral treatment included (a) a voucher incentive program for providing opioid-free urine samples and engaging in verifiable therapeutic activities and (b) the community reinforcement approach, a multicomponent behavioral treatment. Standard treatment included lifestyle counseling. Fifty-three percent of the patients receiving behavioral treatment completed treatment, versus 20% receiving standard treatment. The percentage of patients achieving 4, 8, 12, and 16 weeks of continuous opioid abstinence were 68, 47, 26, and 11 for the behavioral group and 55, 15, 5, and 0 for the standard group, respectively. Behavioral treatment improved outcomes during outpatient detoxification.

Adult

Cocaine use can increase cigarette smoking: evidence from laboratory and naturalistic settings.

Two studies examined the effects of cocaine use on cigarette smoking. Study 1 was conducted with 10 healthy volunteers under controlled laboratory conditions. Participants received double-blind doses of intranasal cocaine HCl (100 mg) or placebo in separate sessions, with each being followed by a 3-hr period of monitored cigarette smoking. Latency to the first cigarette and the mean interval between cigarettes was significantly shorter and the total number of cigarettes smoked was greater after cocaine than placebo administration. Study 2 was conducted by using urine specimens from 9 ambulatory cocaine-dependent patients. Urine cotinine (nicotine metabolite) levels on days when urinalysis testing indicated recent cocaine use were compared with levels on days when urinalysis testing indicated no recent use. Cotinine levels were significantly higher on cocaine-positive days, indicating that cocaine use was associated with greater cigarette smoking. Overall results provide evidence that acute cocaine administration can increase cigarette smoking.

Adolescent

Exudative lung injury is associated with decreased levels of surfactant proteins in a rat model of meconium aspiration.

OBJECTIVE: Meconium aspiration syndrome remains a common cause of respiratory failure in neonates. The acute effects of meconium aspiration are inactivation of lung surfactant in vivo and in vitro. This study investigated the delayed effects of meconium on alveolar surfactant phospholipids and protein levels in spontaneously breathing animals. METHODS: Twenty-two adult rats were given 4.3 mg of dry weight human meconium after endotracheal intubation. Rats were briefly mechanically ventilated in room air, extubated, then killed after 16 (n = 6), 24 (n = 6), 48 (n = 6), and 72 hours (n = 4). Control animals received the same volume of normal saline (n = 7) or no meconium (n = 7). Bronchoalveolar lavage and tissue specimens were evaluated for inflammatory cells, total proteins, surfactant phospholipids, and surfactant proteins. RESULTS: Meconium caused exudative lung injury that was reflected in increased cell counts and proteins in alveolar lavage fluid. The peak injury occurred at 16 hours after instillation, whereas recovery occurred by 72 hours. Although total lavage fluid phospholipids did not change over time, phospholipid and dipalmitoyl phosphatidylcholine in large aggregates tended to decrease at 24 hours. Western blot analysis demonstrated time-dependent qualitative decreases in surfactant proteins A and B (SP-A, SP-B) in meconium-instilled animals compared with the controls. ELISA for SP-B confirmed the Western blot findings with total SP-B in large aggregate decreasing from 25 +/- 4 microg in controls to 6.6 +/- 0.8 microg at 24 hours of injury. CONCLUSIONS: Our study suggests that the exudative lung injury with meconium instillation is associated with decreased levels of SP-A and SP-B in the large aggregate fraction of lung surfactant. We speculate that decreased secretion and/or increased degradation accounts for lower levels of SP-B in bronchoalveolar lavage fluid.

Animals

Sustained cocaine abstinence in methadone maintenance patients through voucher-based reinforcement therapy.

BACKGROUND: Chronic cocaine abuse remains a serious and costly public health problem. This study assessed the effectiveness of a voucher-based reinforcement contingency in producing sustained cocaine abstinence. METHODS: A randomized controlled trial compared voucher-based reinforcement of cocaine abstinence to noncontingent voucher presentation. Patients were selected from 52 consecutively admitted injecting heroin abusers in a methadone maintenance treatment program. Patients with heavy cocaine use during baseline period (N = 37) participated. Except where otherwise indicated, the term cocaine abuse is used in this article in a generic sense and not according to the DSM-III-R definition. Patients exposed to abstinence reinforcement received a voucher for each cocaine-free urine sample (ie, negative for benzoylecgonine) provided three times per week throughout a 12-week period; the vouchers had monetary values that increased as the number of consecutive cocaine-free urine samples increased. Control patients received noncontingent vouchers that were matched in pattern and amount to the vouchers received by patients in the abstinence reinforcement group. RESULTS: Patients receiving vouchers for cocaine-free urine samples achieved significantly more weeks of cocaine abstinence (P = .007) and significantly longer durations of sustained cocaine abstinence (P = .001) than controls. Nine patients (47%) receiving vouchers for cocaine-free urine samples achieved between 7 and 12 weeks of sustained cocaine abstinence; only one control patient (6%) achieved more than 2 weeks of sustained abstinence. Among patients receiving vouchers for cocaine-free urine samples, those who achieved sustained abstinence ( > or = 5 weeks) had significantly lower concentrations of benzoylecgonine in baseline urine samples than those who did not achieve sustained abstinence (P < or = .01). Patients receiving voucher reinforcement rated the overall treatment quality significantly higher than controls (P = .002). CONCLUSION: Voucher-based reinforcement contingencies can produce sustained cocaine abstinence in injecting polydrug abusers.

Adult

Alcohol pretreatment increases preference for cocaine over monetary reinforcement.

Non-dependent cocaine users participated in a two-phase experiment conducted under controlled laboratory conditions. During phase 1, subjects sampled intranasal cocaine (100 mg) and placebo (96 mg lactose + 4 mg cocaine) in separate sessions and under double-blind conditions. Sampling sessions were followed by a single choice session in which subjects made a maximum of ten choices between 10 mg unit doses of cocaine or placebo. Only subjects who reliably (> or = 70%) chose cocaine over placebo in phase 1 participated in phase 2. During phase 2, subjects participated in a series of nine experimental sessions conducted on different days in which they were pretreated with varying doses of alcohol (placebo, 0.5, and 1.0 g/kg) and made a maximum of ten choices between 10 mg unit doses of cocaine and an alternative reinforcer (i.e., varying amounts of money). Visual-analog ratings of drug effects and cardiac function were monitored across all experimental sessions. Cocaine was reliably chosen over placebo by the majority (9 of 11) of subjects during phase 1, demonstrating that the drug functioned as a reinforcer. During phase 2, alcohol pretreatment significantly increased choice of cocaine over the alternative reinforcer, while increasing monetary value decreased cocaine choice. Ratings on some visual-analog scales (e.g., good effects) paralleled cocaine choice, with alcohol pretreatment increasing ratings and greater monetary value decreasing them. Cardiac output increased above baseline levels across all alcohol and monetary conditions, but maximal effects were observed during sessions involving pretreatment with the active alcohol doses. Overall, these results demonstrate (a) that alcohol can increase preference for cocaine over alternative reinforcers and thereby may thwart efforts to reduce or abstain from cocaine use, (b) that availability of an alternative, non-drug reinforcer can effectively decrease preference for cocaine, and (c) that combined use of alcohol and cocaine increases cardiac risk compared to use of cocaine alone.

Adult

A comparison of cocaine-dependent cigarette smokers and non-smokers on demographic, drug use and other characteristics.

Cigarette smoking (n = 156) and non-smoking (n = 43) individuals seeking out-patient treatment for cocaine-dependence were compared on demographic, drug use and other variables. Smokers were younger, less educated, earned less money, began cocaine use at an earlier age, used cocaine more frequently, were more likely to inject or smoke cocaine, were more likely to report legal troubles and having harmed someone physically as consequences of their cocaine use, and had more severe employment and legal problems than non-smokers as measured by the Addiction Severity Index. Smoking remained a significant predictor of more frequent cocaine use, using more grams of cocaine per week and using cocaine via an injection or smoking route even after adjusting for demographic differences between smokers and non-smokers via regression analyses. Smoking status was not significantly related to treatment outcome. Overall, these results indicate that cocaine-dependent smokers represent a more high-risk group than non-smokers. This relationship between smoking, cocaine use, and associated problems merits further investigation.

Adult

Increasing opiate abstinence through voucher-based reinforcement therapy.

Heroin dependence remains a serious and costly public health problem, even in patients receiving methadone maintenance treatment. This study used a within-subject reversal design to assess the effectiveness of voucher-based abstinence reinforcement in reducing opiate use in patients receiving methadone maintenance treatment in an inner-city program. Throughout the study subjects received standard methadone maintenance treatment involving methadone, counseling, and urine monitoring (three times per week). Thirteen patients who continued to use opiates regularly during a 5-week baseline period were exposed to a 12-week program in which they received a voucher for each opiate-free urine sample provided: the vouchers had monetary values that increased as the number of consecutive opiate-free urines increased. Subjects continued receiving standard methadone maintenance for 8 weeks after discontinuation of the voucher program (return-to-baseline). Tukey's posthoc contrasts showed that the percentage of urine specimens that were positive for opiates decreased significantly when the voucher program was instituted. (P < or = 0.01) and then increased significantly when the voucher program was discontinued during the return-to-baseline condition (P < or = 0.01). Rates of opiate positive urines in the return-to-baseline condition remained significantly below the rates observed in the initial baseline period (P < or = 0.01). Overall, the study shows that voucher-based reinforcement contingencies can decrease opiate use in heroin dependent patients receiving methadone maintenance treatment.

Adult

Developmental changes in renal artery blood flow velocity during the first three weeks of life in preterm neonates.

Changes in color Doppler imaging measurements of renal artery blood flow velocity have been reported previously during fetal life and during the first week postnatally in term and preterm infants. This study reports longitudinal, developmental changes in renal artery and aortic blood flow velocities occurring postnatally, from birth to day 1 of life, at 1 week, and at 2 to 3 weeks of age in 14 premature babies (mean gestation, 30 +/- 4 (SD) weeks; birth weight, 1.45 +/- 0.57 kg), and identified by means of color Doppler imaging and pulsed Doppler spectral analysis. Results indicate that a significant increase in renal artery systolic blood flow velocity occurs within the first week of life (from 40 +/- 3 (SEM) cm/sec at birth or on day 1, to 53 +/- 3 cm/sec on day 7, to 51 +/- 4 cm/sec on day 14 to 21; repeated-measures analysis of variance, p = 0.004), concurrently with a significant increase in abdominal aortic blood flow velocities, both systolic (from 40 +/- 4 at birth or on day 1, to 70 +/- 8 on day 7, to 76 +/- 8 cm/sec on day 14 to 21; p <0.001) and diastolic (from 4 +/- 2 at birth or on day 1, to 11 +/- 2 on day 7, to 11 +/- 2 cm/sec on day 14 to 21; p = 0.00 1). Systemic blood pressure did not increase concomitantly during the some period. Neither the presence of respiratory distress syndrome or patent ductus arteriosus nor treatment with indomethacin altered developmental increases in observed renal artery blood flow velocities. The presence of an umbilical artery catheter in the high thoracic position in five infants, however, created turbulence at the level of the renal arteries, significantly increasing renal artery systolic flow velocity from 32 +/- 4 to 44 +/- 5 cm/sec (p = 0.009) and increasing renal resistive index from 0.90 +/- 0.03 to 0.96 +/- 0.04 (p = 0.046). These results suggest that renal artery blood flow velocity increases during the first postnatal week in preterm infants and is likely related to increases in aortic blood flow velocity and reduction in renal vascular resistance.

Analysis of Variance

Meconium increases surfactant secretion in isolated rat alveolar type II cells.

One of the underlying causes of pathophysiology of meconium aspiration syndrome is access of meconium to the alveolar space and inhibition of activity of lung surfactant. This study examines the effects of meconium on type II cell function by following surfactant secretion. Isolated rat alveolar type II cells were labeled with [methyl-3H]choline during the initial 21-22 h of incubation. During the subsequent 150 min of incubation, phosphatidylcholine (PC) secretion in the presence of 1% meconium was increased 250 +/- 11% (mean +/- SE, n = 23) over controls. The secretagogue effect was concentration-dependent and reached a maximum at 0.5% meconium. The meconium effect was not due to cellular toxicity as evaluated by vital dye exclusion, lactate dehydrogenase release, and PC synthesis. The secretagogue effect of meconium was associated with the particulate fraction pelleted by centrifugation of the suspension for 1 h at 100,000 x g. Heat treatment of meconium decreased the effect, suggesting the active component to be a protein. The effect of meconium was additive with that of 0.1 mM terbutaline, or 1 mM ATP, suggesting different pathways of action of each agent. The effect of meconium was reduced in the presence of 0.1 mM 4,4'-diisothiocyanato-2,2'-disulfonic acid, or 100 ng/mL surfactant protein A. These agents were previously shown to inhibit surfactant secretion in a stimulus-independent manner. Our results suggest that meconium at low concentrations is not toxic to type II cells, and a component of meconium, possibly a protein, increases PC secretion.

Animals

An experimental comparison of three different schedules of reinforcement of drug abstinence using cigarette smoking as an exemplar.

The efficacy of three different schedules of reinforcement for promoting and sustaining drug abstinence was compared in this study. Cigarette smoking was studied as an exemplar of stimulant drug self-administration. Sixty cigarette smokers were assigned to one of three groups (progressive rate of reinforcement, fixed rate of reinforcement, and yoked control). Participants in all three groups were asked to refrain from smoking for 1 week. Participants in the progressive and fixed groups achieved greater mean levels of abstinence than those in the control group. Participants in the progressive group were significantly less likely to resume smoking when they became abstinent than participants in the other groups.

Adolescent

The behavioral economics of concurrent drug reinforcers: a review and reanalysis of drug self-administration research.

In economics, goods can function as substitutes, complements, or be independent of one another. These concepts refer to increases, decreases, or no change in the consumption of one item as the price of a second item increases. This review examined whether these economic terms can be used to describe relationships between concurrently available reinforcers in drug self-administration research. Sixteen drug self-administration studies that examined the effects of concurrent reinforcers were identified through a MEDLINE search. Across these studies, the following substances were employed: caffeinated coffee, cocaine, etonitazene, ethanol, heroin, food, methadone, morphine, nicotine cigarettes, pentobarbital, phencyclidine, sucrose and water. These studies were reanalyzed and the results were shown to be consistent with these economic notions. These analyses also showed that relationships among the concurrently available reinforcers were reliable within and across studies, that concurrently available reinforcers can affect each other asymmetrically, and that the relative price may determine the magnitude of effect for substitutes. These findings suggest that these economic concepts may be useful in characterizing the type and magnitude of interactions between concurrently available reinforcers and may suggest potential mechanisms that determine these relationships.

Alcohol Drinking

Incentives improve outcome in outpatient behavioral treatment of cocaine dependence.

OBJECTIVE: To assess whether incentives improved treatment outcome in ambulatory cocaine-dependent patients. METHOD: Forty cocaine-dependent adults were randomly assigned to behavioral treatment with or without an added incentive program. The behavioral treatment was based on the Community Reinforcement Approach and was provided to both groups. Subjects in the group with incentives received vouchers exchangeable for retail items contingent on submitting cocaine-free urine specimens during weeks 1 through 12 of treatment, while the group without incentives received no vouchers during that period. The two groups were treated the same during weeks 13 through 24. RESULTS: Seventy-five percent of patients in the group with vouchers completed 24 weeks of treatment vs 40% in the group without vouchers (P = .03). Average durations of continuous cocaine abstinence documented via urinalysis during weeks 1 through 24 of treatment were 11.7 +/- 2.0 weeks in the group with vouchers vs 6.0 +/- 1.5 weeks in the group without vouchers (P = .03). At 24 weeks after treatment entry, the voucher group evidenced significantly greater improvement than the no-voucher group on the Drug scale of the Addiction Severity Index (ASI), and only the voucher group showed significant improvement on the ASI Psychiatric scale. CONCLUSIONS: Incentives delivered contingent on submitting cocaine-free urine specimens significantly improve treatment outcome in ambulatory cocaine-dependent patients.

Adult