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Biomedical subjects

R J Lamb

Publications and source records attributed to R J Lamb.

At least 55 records · Page 3Linked to original sources
PubMed1997

Multielemental stimulus control: effects of saccharin concentration on a discriminated morphine-saccharin taste aversion.

The effects of saccharin concentration on the stimulus control by a compound stimulus consisting of morphine, saccharin (0.01, 0.03, or 0.10%, wt/vol), and a ball bearing drinking nozzle in a discriminated taste aversion (DTA) procedure were examined in rats (Rattus norvegicus). In paired rats injections of lithium followed presentation of this compound stimulus, whereas in unpaired rats saline injections followed this stimulus. DTA acquisition was more rapid at higher saccharin concentrations. In testing with each individual stimulus element, stimulus control was clearly exerted by all 3 stimulus elements. When another stimulus element was presented jointly with saccharin, behavioral control was similar to that of saccharin alone. Behavioral control by saccharin increased with saccharin concentration. However, behavioral control by the 2 other stimulus elements was relatively unaffected when the saliency of the saccharin element was increased.

Animals↗
PubMed1996

Decline in self-reported dysphoria after treatment entry in inner-city cocaine addicts.

This study examined self-reported dysphoria in 82 consecutive admissions to intensive outpatient treatment for cocaine abuse on whom data for the Beck scales for depression, anxiety, and hopelessness were available for intake and 4 subsequent weeks with no more than 1 missing data point. Mean scores on the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI) decreased significantly between intake and Week 1, with no further significant changes from Weeks 1-4. Similar drops in the rate of clinically significant BDI and BAI scores also were observed. Scores on the Beck Hopelessness Scale (BHS) showed no significant changes. By Week 4, rates of clinically significant depression, anxiety, and hopelessness were similar (17%, 13%, and 16%, respectively). These findings suggest that assessing depression and anxiety using the BDI and BAI in this population should be postponed for at least 1 week after intake and that intake levels of self-reported mood may be inappropriate baseline measures for evaluating treatment effects.

Adult↗
PubMed1996

The accelerated intake: a method for increasing initial attendance to outpatient cocaine treatment.

We examined whether offering an accelerated (same-day) versus a standard (1- to 7-day delay) intake appointment increased initial attendance at an outpatient cocaine treatment program. Significantly more of the subjects who were offered an accelerated intake (59%) attended than those who were given a standard intake (33%), chi 2 (2, N = 78) = 4.198, p < .05. The accelerated intake procedure appears to be useful for enhancing enrollment in outpatient addiction treatment.

Adolescent↗
PubMed1995

Reduced surface expression of transforming growth factor beta receptor type II in mitogen-activated T cells from Sézary patients.

Sézary syndrome (SzS), the leukemic form of cutaneous T-cell lymphoma, is characterized by clonal proliferation of CD4+ T cells and immune dysfunctions, raising the possibility of cytokine-related abnormalities. We previously described a decreased response to the growth-inhibitory effects of transforming growth factor type beta (TGF-beta) in SzS T cells accompanied by apparent loss of surface type II TGF-beta receptor (TGF beta RII). To specifically determine if defects exist in TGF beta RII protein expression and/or transport in SzS patients, we developed a sensitive flow cytometric method to detect TGF beta RII on the surface and intracellularly in the CD4+ T cells. Our results indicate that unlike normal CD4+ T cells, CD4+ T cells from 9 of 12 SzS patients expressed little, if any, surface TGF beta RII in response to mitogen stimulation. At the intracellular level, however, pools of TGF beta RII were comparable to those in normal CD4+ T cells. This indicates that defective trafficking of this inhibitory cytokine receptor may contribute significantly to the development of this disease.

Base Sequence↗
PubMed1995

Cocaine use and HIV risk behavior in methadone maintenance patients.

This study examined sexual and drug use behavior in 247 methadone maintenance patients, to explore the association of cocaine use with human immunodeficiency virus (HIV) risk behavior. In univariate analyses, cocaine use was positively associated with any drug injection, number of injections, and sexual intercourse without condoms. These relationships remained significant after controlling for other drug use and demographic factors. Heroin use also contributed to injection-related risk. We conclude that cocaine use represents a continued source of risk for exposure to HIV in this population, and that more aggressive efforts are warranted to reduce illicit drug use, particularly of heroin and cocaine, in methadone patients.

Adult↗
PubMed1995

Results of the NIDA treatment demonstration grants' cocaine workgroup: characteristics of cocaine users and HIV risk behaviors.

This journal issue includes seven articles (six plus this introduction) from the "cocaine workgroup" of the National Institute on Drug Abuse (NIDA) treatment demonstration grants. In this introduction, results of the first attempts to compare data from seven disparate demonstration grant sites are summarized: Overall, rates of recent cocaine use were high in all locations, injection drug use was common, age of first drug use was between 14 and 17 years with age of first cocaine use between 20 and 25 years, arrests were common at all sites especially among cocaine injectors, and polydrug use was the norm. Interestingly, both gender and ethnic status were significantly associated with polydrug use and marijuana use among the cocaine users. These results indicated that it is possible to define variables precisely for analysis across sites and laid the groundwork for the next set of analyses in which the common theme of human immunodeficiency virus (HIV) risk behaviors among cocaine abusers was agreed upon. This next set of analyses are included in the following six papers. Overall, these reports confirm recent data about the association of cocaine use with HIV risk behaviors. They extend considerably the literature on the association of cocaine with HIV risk behaviors, and the report from New York in which therapeutic community treatment was shown to be feasible and possibly useful to methadone clients represents an interesting and new finding. In conclusion, cross-site collaborations can take different forms and this collection of papers represents one successful approach.

Adolescent↗
PubMed1995

Stages and processes of change among polydrug users in methadone maintenance treatment.

We applied the stages-of-change model of Prochaska and DiClemente to the problem of drug use among methadone maintenance patients to examine correlates of different stages of treatment readiness. The 276 subjects were divided into stage categories based on self-reported drug use and questionnaire responses regarding plans to discontinue unauthorized drug use in the future. Confirmatory factor analytic procedures validated four process scales derived from a 60-item questionnaire. Each stage was characterized by a profile of change-process scores largely consistent with predictions, though these scores did not distinguish stages as clearly as has been reported in previous research. Analysis of subject characteristics revealed that those in the Precontemplation stage reported significantly longer treatment tenures than subjects in any other stage besides Maintenance.

Adult↗
PubMed1995

Situations occasioning cocaine use and cocaine abstinence strategies.

We interviewed 265 cocaine-experienced methadone patients about situations that occasioned their cocaine use and strategies they used to avoid cocaine use. Subjects identified an average of 15 situations that occasioned cocaine use. The three most frequently identified were having the drug present (86% of subjects), being offered the drug (85%) and having money available (83%). Subjects reporting fewer situations also reported longer periods of lifetime abstinence (p < 0.01). A principal components analysis extracted 10 groups of situations that were most frequently identified in combination. Subjects identified a median of seven strategies for avoiding cocaine use; however, there was large inter-subject variability. This variance was not accounted for by demographic variables, employment status or treatment experience. The three strategies identified most frequently were avoiding people and places (81%), thinking about what they could lose (76%) and leaving the situation (66%). The total number and type (reactive vs. proactive) of strategies identified by subjects had no relationship to cocaine abstinence, although four specific strategies (thinking about what could be lost, leaving the situation, moving to a new area and using a different drug) were positively correlated with cocaine abstinence. We discuss implications of these results for clinical practice.

Adult↗
PubMed1994

Human d-amphetamine drug discrimination: methamphetamine and hydromorphone.

Standard measures of subjective and discriminative effects of drugs were compared in 5 human volunteers. Subjects responded on a second-order color-tracking procedure, where 30 mg of d-amphetamine served as a discriminative stimulus for one response and its absence as the discriminative stimulus for another response. Self-reported subjective effects were assessed concurrently using the single-dose questionnaire, subscales of the Addiction Research Center Inventory, and several analogue rating scales. On different days following discrimination acquisition, varying doses of d-amphetamine, methamphetamine, and hydromorphone were administered. In these test sessions, either response was reinforced. Methamphetamine and d-amphetamine occasioned dose-related increases in d-amphetamine appropriate responding; hydromorphone did not. Methamphetamine and d-amphetamine occasioned dose-related increases in reports of the drug received being most like "speed"; hydromorphone occasioned dose-related increases in reports of the drug received being most like "dope." All three drugs occasioned dose-related increases in reports of drug liking, and increases in the morphine-benzedrine group, amphetamine, and benzedrine group scales of the Addiction Research Center Inventory. This experiment demonstrated that although explicit discriminative control of behavior by a drug may covary with drug identification, it does not necessarily covary with other self-reported subjective effects. Thus, the complementary nature of the data provided by drug discrimination and standard subjective-effects measures provides quantitative and qualitative data useful in studying both relatively novel compounds and the behavioral biology of psychoactive drugs in general.

Adult↗
PubMed1993

Behavioral effects of pentobarbital, lorazepam, ethanol and chlorpromazine substitution in pentobarbital-dependent baboons.

Baboons were given continuous intragastric infusions of 100 mg/kg/day of pentobarbital before and during these experiments. The baboons responded under a fixed-ratio (FR) 30-response schedule of food presentation from 10:00 A.M. of one day to 8:00 A.M. of the next day. Terminating pentobarbital administration (i.e., substituting water for pentobarbital) from 8:00 A.M. of one day to 8:00 A.M. of the next day produced large decreases in the number of pellets earned. Repeated 24-h terminations of pentobarbital administration at 1-week intervals produced similar decreases in the pellets earned. In another experiment, the effects of terminating pentobarbital administration for several days were examined. The number of pellets earned decreased within 2 h of terminating pentobarbital administration was maximally suppressed during the first day, and recovered over 3 to 5 days. When different doses of pentobarbital were substituted for 24 h, the disruption of responding seen after pentobarbital termination was attenuated in a dose-dependent manner. In another experiment, the effects of substituting lorazepam, ethanol or chlorpromazine for pentobarbital for 24 h were examined. Lorazepam produced a dose-dependent attenuation of the effects of pentobarbital termination, whereas ethanol did not. Chlorpromazine did not attenuate the effects of pentobarbital termination in two of the three baboons tested, and produced erratic results in the third.

Animals↗
PubMed1992

Transforming growth factor-beta inhibits human T-cell proliferation through multiple targets.

This study investigates further the inhibitory effects of transforming growth factor-beta (TGF-beta) on human T-lymphocyte responses to mitogenic stimulation. T cells were stimulated either with mitogenic concentrations of PHA or with submitogenic concentrations of Con A followed by the addition of IL-2. DNA synthesis ([3H]thymidine incorporation) in both systems was inhibited by 60-69% in the presence of TGF-beta, with maximal reduction occurring on days 4 and 5 of culture. Cell surface expression of transferrin receptor (TfR) and IL-2 receptor-alpha (p55) were inhibited by 20-80% in the Con A/rIL-2 system and 20-45% in the PHA system in the presence of TGF-beta. In addition, mitogen-induced up-regulation of TfR and IL-2R mRNA levels were inhibited by TGF-beta. Finally, we investigated the effect of TGF-beta on the assembly of clathrin monomers into assembled coated pits and vesicles, and essential step in TfR and IL-2R alpha turnover. Stimulation of T cells using either mitogen system resulted in an increase in the level of assembled clathrin, which was almost completely inhibited by TGF-beta. These findings suggest that TGF-beta may act at several sites in mitogen-mediated proliferative pathways to contribute to the inhibition of T-cell proliferation.

Clathrin↗
PubMed1991

Protein kinase C regulates both production and secretion of interleukin 2.

Inhibiting protein kinase C (PKC) activity abrogated interleukin 2 (IL2) production by mitogen-stimulated human T lymphocytes. This effect was due partially to a 50% decrease in IL2 gene expression. However, when PKC inhibitors were added after IL2 gene transcription had already proceeded for 3-4 h, the IL2 in the culture supernatants was still reduced by 30-80%, and intracellular IL2 was increased by up to 50%. The inhibition of PKC affected the expression of IL2 receptors by these cells differently; it had little effect on gene expression or on the membrane-bound form of the receptor, but it decreased soluble receptors in the supernatants by 50-80%. These data indicate that in addition to its previously defined role in gene expression, PKC can also regulate extracellular secretion of proteins critical for T cell proliferation.

Alkaloids↗
PubMed1991

Self-injection of barbiturates, benzodiazepines and other sedative-anxiolytics in baboons.

Self-injection of 12 sedative-anxiolytics was examined in baboons. Intravenous injections and initiation of a 3-h time-out were dependent upon completion of a fixed-ratio schedule requirement, permitting eight injections per day. Before testing each dose of drug, self-injection performance was established with cocaine. Subsequently, a test dose was substituted for cocaine. At some doses, all five of the benzodiazepines examined (alprazolam, bromazepam, chlordiazepoxide, lorazepam, triazolam) maintained rates (number of injections per day) of drug self-injection above vehicle control in each of the baboons tested. Maximum rates of benzodiazepine self-injection were generally submaximal. Of the benzodiazepines examined, triazolam maintained the highest rates of self-injection. Among the three barbiturates tested, methohexital generally maintained high rates of self-injection in contrast to hexobarbital and phenobarbital, which only maintained low rates. Of the four non-benzodiazepine non-barbiturate sedatives examined, both chloral hydrate and methyprylon occasionally maintained high rates of self-injection. Although there were differences within and across animals, baclofen maintained intermediate rates of self-injection. The novel anxiolytic buspirone maintained only low rates of self-injection that were not different from vehicle. This study further validates the self-injection methodology for assessing sedative-anxiolytic abuse liability and provides new information about drug elimination rate as a determinant of drug self-administration.

Animals↗
PubMed1991

The reinforcing and subjective effects of morphine in post-addicts: a dose-response study.

The reinforcing and subjective effects of morphine were determined in five human volunteers with histories of i.v. heroin abuse. Subjects responded under a second-order schedule of i.m. injection. Under this schedule, every 100 lever presses produced a brief stimulus light [fixed ratio (FR) 100:s]; the 30th completion of the FR 100 requirement turned on the light for 15 min and the subject received an i.m. injection of morphine [FR 30 (FR 100:s)]. Once each weekday morphine or placebo was available under this schedule. Each drug dose was available for 1 week. Under these conditions placebo did not maintain responding; 3.75 mg of morphine maintained responding in four of five subjects, and higher morphine doses (7.5, 15 and 30 mg) maintained responding in all five subjects. Subjective effects were measured concurrently: these included measures of drug liking, the Morphine Benzedrine Group scale of the Addiction Research Center Inventory, drug detection and identification. Subjects did not report subjective effects different from placebo for the lowest dose of morphine; the intermediate doses of morphine produced inconsistent effects, and the highest dose of morphine occasioned reports of drug liking and "dope" identifications. These results indicate that there can be a significant dissociation of the reinforcing and the subjective effects of opioids, which has implications for theories of opioid abuse, particularly those assuming that the reinforcing effects are causally related to the euphoric effects of opioids. Furthermore, these results confirm that measures of reinforcing effects and measures of subjective effects do not necessarily lead to identical predictions when used to assess the liability for abuse of a substance.

Analgesia, Patient-Controlled↗
PubMed1990

Self-administration in baboons and the discriminative stimulus effects in rats of bupropion, nomifensine, diclofensine and imipramine.

The behavioral effects of the antidepressants nomifensine, diclofensine, bupropion, and imipramine were examined using a cocaine substitution drug self-administration procedure in baboons and a cocaine drug discrimination procedure in rats. Intravenous self-administration of the antidepressants was examined in baboons under conditions in which baseline responding was maintained by intravenous injections of cocaine HCl (0.32 mg/kg/injection). Drug was available under a fixed-ratio 80-response or 160-response schedule of intravenous injection. Each drug injection was followed by a 3-h time-out allowing a maximum of eight injections per day. The antidepressants or their vehicles were substituted for cocaine for a period of 15 days, followed by a return to the cocaine baseline. Nomifensine, diclofensine and bupropion all maintained self-administration behavior at levels above those maintained by their respective vehicles. Some doses of nomifensine, diclofensine, and bupropion maintained levels of behavior similar to those maintained under baseline cocaine conditions. High doses of imipramine maintained levels of behavior above those maintained by its vehicle, but the amount of behavior maintained under these conditions was extremely small. In a second experiment rats were trained to discriminate 32 mumol/kg cocaine (IP 10 min presession) from no drug in a two-lever food reinforced drug discrimination procedure in which responding on one lever was reinforced following ten consecutive responses when the session was preceded by cocaine administration, while responding on the other lever was similarly reinforced in the absence of cocaine pretreatment. Cocaine, nomifensine, diclofensine, and bupropion all dose-dependently occasioned cocaine-appropriate responding. Imipramine did not occasion cocaine-appropriate responding over a range of behaviorally active doses.

Animals↗
PubMed1990

Tuberculosis, AIDS, and i.v. drug abuse.

The number of tuberculosis cases reported has begun to rise. This rise in the number of cases may be due to HIV infection, particularly among intravenous drug abusers.

Acquired Immunodeficiency Syndrome↗