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Biomedical subjects

T L Thompson

Publications and source records attributed to T L Thompson.

At least 19 recordsLinked to original sources
PubMed1996

Efficacy of a therapeutic cocaine vaccine in rodent models.

Cocaine abuse is a major medical and public health concern in the United States, with approximately 2.1 million people dependent on cocaine. Pharmacological approaches to the treatment of cocaine addiction have thus far been disappointing, and new therapies are urgently needed. This paper describes an immunological approach to cocaine addiction. Antibody therapy for neutralization of abused drugs has been described previously, including a recent paper demonstrating the induction of anti-cocaine antibodies. However, both the rapidity of entry of cocaine into the brain and the high doses of cocaine frequently encountered have created challenges for an antibody-based therapy. Here we demonstrate that antibodies are efficacious in an animal model of addiction. Intravenous cocaine self-administration in rats was inhibited by passive transfer of an anti-cocaine monoclonal antibody. To actively induce anti-cocaine antibodies, a cocaine vaccine was developed that generated a high-titer, long-lasting antibody response in mice. Immunized mice displayed a significant change in cocaine pharmacokinetics, with decreased levels of cocaine measured in the brain of immunized mice only 30 seconds after intravenous (i.v.) administration of cocaine. These data establish the feasibility of a therapeutic cocaine vaccine for the treatment of cocaine addiction.

Animals↗
PubMed1995

In vivo stimulated dopamine release in the nucleus accumbens: modulation by the prefrontal cortex.

In vivo voltammetry was used to measure stimulated dopamine (DA) release in the nucleus accumbens following 6-hydroxydopamine (6-OHDA) lesions of the medial prefrontal cortex (PFC). Lesions of the PFC resulted in a significant potentiation of K(+)-stimulated DA release (383% of control). These data are in agreement with other studies which suggest DAergic activation of cortical sites can alter the activity of DAergic neurons at subcortical sites. Specifically these results suggest that DAergic nerve terminals in the nucleus accumbens are tonically inhibited by DAergic activity in the PFC and that alleviation of this tonic inhibition produces hyperresponsiveness in the nucleus accumbens.

Animals↗
PubMed1995

Recognizing and managing depression in primary care.

Depression is a common disorder in the primary care setting; it is associated with considerable distress and dysfunction. The management of depressed primary care patients can be complicated by the fact that these patients may lack insight into the cause of their symptoms and report only the somatic manifestations of their disorder to their physicians. Primary care patients may also be reluctant to accept a diagnosis of depression or referral to a mental health specialist. Primary care physicians may feel they lack the time or the training to adequately address their patients' depressive disorders. This paper presents a model for identifying, evaluating, and treating depression which has been specifically developed to help primary care physicians overcome these barriers.

Antidepressive Agents↗
PubMed1995

Reproducibility of the Glaucoma-scope in cadaver eyes.

We evaluated the intra- and inter-observer variability of depth measurements of the optic disc in cadaver eyes using the Glaucoma-scope. Intra-observer variation of 10 separately captured images became significantly greater with increasing depth of the optic cup (p < 0.001). The standard deviation of depth measurements were 9.06 mu over the neural rim, 25.00 mu along the cup wall, and 40.94 mu at the bottom of the optic cup. However, intra-observer variation of a single captured image did not increase with greater optic cup depth. Intra-observer variation, but not inter-observer variation, generally was greater when measuring the superior than inferior optic disc (p < 0.05). This study suggests that when capturing separate optic disc images with the Glaucoma-scope, increased variation in depth measurements can be expected with greater optic cup depth and in the superior portion of the optic disc.

Cadaver↗
PubMed1994

Estrogen regulation of dopamine release in the nucleus accumbens: genomic- and nongenomic-mediated effects.

The ability of estrogen to modulate mesolimbic dopamine (DA) was examined using in vivo voltammetry. Estrogen priming (5 micrograms, 48 h) of ovariectomized (ovx) female rats resulted in a slight decrease in K(+)-stimulated DA release measured in the nucleus accumbens: this decrease was accompanied by a significant increase in both DA reuptake and DA clearance times. Following estrogen priming nomifensine, a potent inhibitor of the DA uptake carrier, was still able to potentiate K(+)-stimulated DA release and alter the time course of DA availability, but the response was attenuated compared with ovx controls. Direct infusion of 17 beta-estradiol hemisuccinate (17 beta-E, 20-50 pg) into the nucleus accumbens resulted in a biphasic potentiation of K(+)-stimulated release. An initial increase in release was observed 2 min after 17 beta-E infusion; this increase, although reduced by 15 min, was still significantly higher than control values. A subsequent potentiation was observed 60 min after the initial 17 beta-E infusion; this response remained for at least an additional 60 min. Nomifensine did not significantly alter K(+)-stimulated DA release following 17 beta-E infusion, but was still able to potentiate the total time DA was available extracellularly. These data suggest that the mesolimbic A10 DA neurons that terminate in the nucleus accumbens can be modulated in vivo by estrogen and that this modulation may be mediated by both genomic (long term) and nongenomic (short term) mechanisms.

Analysis of Variance↗
PubMed1993

Testicular weight, Sertoli cell number, daily sperm production, and sperm output of sexually mature rabbits after neonatal or prepubertal hemicastration.

The present study was conducted to investigate the influence of hemicastration and age at hemicastration on the subsequent testicular development of male rabbits through sexual maturity. Thirty New Zealand white rabbits were left intact or were hemicastrated on Day 35, 49, 77, or 105 postconception. Beginning at 7 mo of age, ejaculates were collected every other day for 1 mo, and the last ten ejaculates were used to quantify daily sperm output. At 8 mo, the rabbits were killed and their carcases, testes, testicular capsules, and epididymides were weighed. Testicular tissue was processed for quantification of sperm production rates by enumeration of homogenization-resistant spermatids and via histometric evaluation. Regardless of the age at hemicastration, this manipulation did not alter the development of the remaining testis as assessed from testis weight, numbers of Sertoli cells per testis, daily sperm production, or sperm output (p > 0.05). On the basis of these findings, it would appear that the development of the spermatogenic capacity of the remaining testis of the rabbit is not altered appreciably by hemicastration at a young age.

Animals↗
PubMed1993

The critical times: meeting parental communication needs throughout the NICU experience.

The parental stresses caused by a premature birth and the NICU experience may create problems in the parent-child relationship. These problems may lead to subsequent difficulty in bonding or parenting, and may even be related to child neglect and abuse. The NICU staff is in a unique position to help minimize parental stress by providing information, support, and understanding to facilitate coping with fear and uncertainty. Parents need help in adjusting their expectations to reality, especially during the early days in the NICU. While the mother is still hospitalized, the father is in an especially vulnerable position, as he may be unprepared to be a primary caregiver, threatened by the female staff, and expected to assume a focal role while he may need comfort himself. Information that is most helpful to parents is that which helps return some control to them. Involving parents in the child's caregiving and in decision making also helps increase parental feelings of control and decrease feelings of stress. Attention should be paid to the questions and nonverbal communication of the parents to ascertain when communication is especially important. Key times during which communication is typically crucial are identified.

Adaptation, Psychological↗
PubMed1992

Effect of Kuwait oil field fires on human comfort and environment in Jubail, Saudi Arabia.

The plumes from the Kuwait oil field fires reduced hemispheric (total) solar radiation by 26-36% during January-June 1991 in Jubail (300 km SE of Kuwait City), Saudi Arabia. Residents feel noticeably cooler even though air temperatures have not been lowered significantly (up to June 1991). These observations support human comfort theories and demonstrate the importance of shade to comfort. The desirability of complete solar radiation measurements, including those of diffuse radiation, is indicated.

Air Pollutants↗
PubMed1991

Concomitant sensitization of amphetamine-induced behavioral stimulation and in vivo dopamine release from rat caudate nucleus.

Rats were treated twice daily either with saline or d-amphetamine (5 mg/kg) for 5 days. When challenged approximately 15 days later with an injection of 0.5 mg/kg amphetamine, the chronic amphetamine animals showed (1) an augmented release of dopamine in the caudate nucleus in vivo and (2) an increase in stereotyped behavior compared to the chronic saline animals. These results suggest that an increase in dopamine release from the caudate may contribute to amphetamine-induced behavioral sensitization.

Animals↗
PubMed1990

Lack of efficacy of hydergine in patients with Alzheimer's disease.

BACKGROUND: There is no effective pharmacologic treatment for Alzheimer's disease, the most common dementing illness in the United States. Hydergine, a combination of ergoloid mesylates, is the only approved medication for Alzheimer's disease, but despite widespread use its efficacy remains to be established. We conducted a clinical trial of Hydergine-LC, a newer preparation of ergoloid mesylates in the form of a liquid in a capsule (LC) that may have greater bioavailability, to determine its value in patients with Alzheimer's disease. METHODS AND RESULTS: Eighty older adults with probable Alzheimer's disease participated in this double-blind, placebo-controlled trial of Hydergine-LC for 24 weeks. The recommended dose of 1 mg orally three times daily was used. Cognition and behavior were evaluated before and after the trial, and the patients were monitored for adverse effects. The medication was safe and well tolerated. The Hydergine-LC group did not perform better after treatment than the placebo group on any test, and its performance was worse (P less than 0.01 and P less than 0.02, respectively) on one cognitive measure (Wechsler Adult Intelligence Scale Digit Symbol Substitution Task) and on one behavioral scale (the Geriatric Evaluation by Relatives Rating Instrument). CONCLUSIONS: Hydergine-LC appears to be ineffective as a treatment for Alzheimer's disease.

Aged↗
PubMed1990

Activation of striatal tyrosine hydroxylase by in vivo electrical stimulation: comparison with cyclic AMP-mediated activation.

These studies were carried out to characterize the activation of rat striatal tyroxine hydroxylase produced by depolarization of the medial forebrain bundle and to evaluate the possible role of cyclic AMP as a mediator of this activation. The enzymatic properties of tyrosine hydroxylase following in vivo depolarization were compared to those produced by treatment of striatal synaptosomes with dibutyryl cyclic AMP (dbcAMP). Similar effects were observed with regard to enzyme distribution, altered sensitivity to dopamine-induced inhibition, and activity as a function of tyrosine concentration. However, differences between the two treatments were also apparent. First, treatment with dbcAMP shifted the pH optimum from 6.2 to 7.0. In contrast, electrical stimulation decreased the rate of decline in activity as the pH was increased above the optimum, but did not shift the pH optimum. Second, plots of tyrosine hydroxylase activity versus cofactor concentration revealed two enzyme forms for both control and electrically stimulated preparations. However, dbcAMP treatment converted the enzyme to a single high affinity form. These results can be explained by one of the following: (1) cyclic AMP is the sole mediator of enzyme activation, but does not produce a maximally activated enzyme following in vivo depolarization, (2) cyclic AMP is only one of several mediators involved or (3) cyclic AMP is not involved in depolarization-induced activation, with activation occurring via the mediation of other intracellular messengers, such as calcium.

Animals↗