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Biomedical subjects

P Terry

Publications and source records attributed to P Terry.

17 recordsLinked to original sources

Differential antagonism of the effects of dopamine D1-receptor agonists on feeding behavior in the rat.

A series of experiments was conducted to examine the effects of dopamine D1 receptor agonists on food intake in rats. In the first experiment, the D1 agonist SKF 38393 (3.0-30.0 mg/kg) dose-dependently suppressed feeding during a 40 min food-access period, both in food-deprived rats and in non-deprived rats fed a highly palatable diet. Non-deprived rats were more sensitive to these effects of SKF 38393. Using the limited-access, food-deprivation procedure, a comparison was made between the anorectic effects of three D1 agonists with differing intrinsic efficacies and receptor selectivities. Rank order of potencies for reducing food intake was SKF 82958 > SKF 77434 > SKF 38393 (ED50 values: 0.7, 3.6 and 15.7 mg/kg, respectively). Dose-related, surmountable antagonism by the D1 antagonist SCH 23390 (0.01 and 0.03 mg/kg) was only obtained with SKF 82958 (0.1-10.0 mg/kg). In contrast to the other compounds, the effects of SKF 38393 were not appreciably altered by the D1 antagonist. The effects of SKF 82958 were also antagonized by the D2 receptor antagonist spiperone (0.05 and 0.1 mg/kg), although not in a dose-dependent manner. The present results support a role for D1 receptors in central feeding mechanisms. They also suggest that the effects of SKF 38393 on feeding may not be mediated exclusively by the D1 receptor and, further, that SKF 38393 may not serve well in behavioral studies as a prototypical D1 agonist. The results also demonstrate the need for comparisons among several compounds in studies of D1 mediated behavioral effects.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben

Comparative behavioral pharmacology and toxicology of cocaine and its ethanol-derived metabolite, cocaine ethyl-ester (cocaethylene).

The present study compared the behavioral and toxic effects of cocaine and its ethanol derived metabolite, cocaine ethyl-ester (cocaethylene). Both drugs produced qualitatively similar psychomotor stimulant effects. Cocaine and cocaethylene increased locomotor activity in mice, with cocaine approximately four times more potent than cocaethylene. The durations of action of ED75 doses of each of the drugs were comparable. Each of the drugs also produced stimulation of operant responding in rats. In rats and squirrel monkeys trained to discriminate cocaine injections from saline, cocaine was approximately three to five times more potent than cocaethylene in producing these cocaine-like interoceptive effects. In contrast to the behavioral effects, cocaine and cocaethylene were equipotent in producing convulsions, and cocaethylene was more potent than cocaine in producing lethality. These results suggest that the conversion of cocaine to cocaethylene with simultaneous cocaine and alcohol use may produce an increased risk of toxicity due to a decrease in the potency of cocaethylene in producing psychomotor stimulant effects, and its increased potency in producing toxicity.

Animals

Differential effects of injection regimen on behavioral responses to cocaine.

Locomotor behavior was measured in mice receiving IP cocaine at 5, 10, 20, or 40 mg/kg. then with 5, 5, 10, and 20 mg/kg at 10-min intervals. In the single-dose treatment, mice received a single dose of cocaine at a time corresponding to the equivalent cumulative dose, with saline injections at other times. The single-injection treatment was similar, but saline injections were omitted. Locomotor activity was measured across each 10-min interval. Mice were retested 6 weeks later and 1 day after that. Dose-response curves were similar for all three treatments on the first test, but diverged markedly on subsequent tests. Significant locomotor sensitization occurred at the higher doses on the second test, particularly in the treatments receiving single cocaine injections. On the third test, convulsions occurred at 40 mg/kg, but only in the singly dosed treatments. The results demonstrate that injection parameters can modify both the behavioral and toxic effects of cocaine.

Animals

Survival in a cohort of human immunodeficiency virus-infected tuberculosis patients in New York City. Implications for the expansion of the AIDS case definition.

BACKGROUND: The occurrence of pulmonary tuberculosis in human immunodeficiency virus (HIV)-infected persons is believed to represent a less severe stage of HIV-related disease with a more favorable prognosis than other acquired immunodeficiency syndrome (AIDS)-defining conditions; therefore, it has been excluded from the AIDS definition established by the Centers for Disease Control (Atlanta, Ga) criteria. METHODS: To determine the prognosis of patients with HIV-related tuberculosis, we assessed the clinical, immunologic, and HIV infection status of a cohort of male subjects aged 20 to 44 years who were hospitalized with tuberculosis but without AIDS in New York City hospitals from 1985 through 1986, and we determined their mortality through May 1991. RESULTS: The 58 patients who agreed to participate were largely (90%) nonwhite and had a high prevalence of pulmonary tuberculosis (90%) and HIV infection (53%). Patients who were HIV seropositive had significantly lower CD4 cell counts (median, 0.136 x 10(9)/L; range, 0.013 x 10(9) to 2.314 x 10(9)/L vs median, 0.765 x 10(9)/L; range, 0.284 x 10(9) to 2.333 x 10(9)/L), and, during the follow-up period, an 83% mortality rate that was 7.5 times higher than the 11% rate in seronegative subjects. Survival analyses revealed that for all HIV-seropositive subjects the probability of death at 30 months was 72% and the median survival was 21 months (95% confidence interval, 15.5 to 26.5 months), while for HIV-seropositive subjects with CD4 cell counts of 0.2 x 10(9)/L or less, the probability of death at 30 months was 92% and the median survival was 15.75 months (95% confidence interval, 14.0 to 17.6 months). CONCLUSION: The prognosis for patients with HIV-related pulmonary tuberculosis is poor, and those with CD4 cell counts of 0.2 x 10(9)/L or less have survival patterns similar to that of patients with AIDS. We believe that these data support the expansion of the AIDS case definition to include persons with both pulmonary tuberculosis and severe HIV-related immunosuppression.

AIDS-Related Opportunistic Infections

The result of an educational intervention for physicians providing HIV-antibody testing and counseling.

Based upon our findings related to physicians' human immunodeficiency virus (HIV) antibody-testing practices in a multispecialty group practice, we randomly selected a group of family practice physicians and over six months provided them with patient education resources and information about HIV-antibody-testing guidelines and their own patient counseling practices. Following this intervention, a chart audit showed that documentation of patient counseling had doubled. We also noted positive, albeit minor, changes in obtaining informed consent. Physicians ordered fewer tests overall; however, we found a slight increase in testing for "inappropriate" reasons.

AIDS Serodiagnosis

Sympathoadrenal effects on extinction of rewarded running in the rat.

Two groups of rats underwent adrenal demedullation or sham surgery before being trained to run in a straight runaway for food reward at a short intertrial interval (90 s). Half of each group of animals were then injected IP with the sympathetic neurotoxin, 6-hydroxydopamine HBr (6-OHDA; 30 mg/kg); the remainder received saline vehicle. After 3 more days of acquisition training, running was extinguished over 12 trials in all rats. Running times were similar in all groups at the start of extinction. In saline-injected animals, extinction proceeded more slowly in the demedullated than in the sham-operated group, but this effect was largely abolished by 6-OHDA. Consistent with previous results, there was evidence that 6-OHDA facilitated extinction, irrespective of adrenal demedullation, but this effect was most apparent in the time taken to emerge from the start-box. The rats were killed two days after the end of the experiment; cardiac noradrenaline levels were depleted by 83% of control values in 6-OHDA-treated animals. The results suggest that the adrenal medulla and sympathetic neurones have opposing and interacting effects on the response to nonreward.

Adrenal Glands

Anxiolytic-like action of beta-blockers: effects of stimulus salience.

Eighteen rats were trained on a multiple schedule: lever pressing was rewarded on a Variable Interval (VI 20 s) in both components but, in addition, punished on a similar schedule in one. Shock intensity was individually adjusted to produce high or low degrees of response suppression during punishment periods in two different groups of animals. For some rats in each group, punishment periods were signalled by a flashing light; for others, by a steady light. d,l-Propranolol (2.5-7.5 mg/kg), l-propranolol (3.75, 7.5 mg/kg) and atenolol (20 mg/kg) released responding in animals in which suppression was low. These effects were restricted to the group for which the punishment signal was flashing light. The results are consistent with the view that activation of peripheral beta-adrenoceptors is involved in the suppression of responding by signals of punishment, but only in some conditions. Adding chlordiazepoxide (3.75 mg/kg) to d,l-propranolol (7.5 mg/kg) increased punished responding in the high-suppression group, but reduced it in the low-suppression group.

Adrenergic beta-Antagonists

Rapid development of ciprofloxacin resistance in methicillin-susceptible and -resistant Staphylococcus aureus.

The fluoroquinolones, particularly ciprofloxacin, have been suggested to treat methicillin-resistant Staphylococcus aureus (MRSA) infections and colonization and methicillin-susceptible S. aureus (MSSA) infections. The development of ciprofloxacin resistance in MRSA and MSSA was prospectively evaluated. After 3 months of ciprofloxacin use, high-level resistance (MIC90, 64 micrograms/ml) developed in MRSA and increased at an alarming rate, from none to 79% over a 1-year period. High-level ciprofloxacin resistance also developed in MSSA, increasing to 13.6% over the same period. Antibiograms, phage typing, and plasmid profile analysis suggest that more than one clone of MRSA developed resistance and that ciprofloxacin resistance is not associated with the acquisition of a new plasmid. Most patients had nosocomial acquisition and about one-half had a history of previous ciprofloxacin use. Ciprofloxacin resistance can develop rapidly in S. aureus; thus, ciprofloxacin appears to have limited usefulness in treating staphylococcal infections and colonization, especially those due to MRSA.

Ciprofloxacin

Behavioral effects of selective dopaminergic compounds in rats discriminating cocaine injections.

The involvement of dopamine receptor subtypes in the discriminative stimulus effects of cocaine was evaluated by the ability of a series of compounds selective for D1 or D2 dopamine receptors to produce discriminative stimulus effects comparable to cocaine. Male, Sprague-Dawley rats were trained to discriminate 10 mg/kg of cocaine HCI from saline in a two-lever discrimination procedure. Inhibitors of catecholamine and serotonin reuptake (GBR 12909, WIN 35,428 and mazindol), d-amphetamine, and the nonselective dopamine agonist, apomorphine, produced dose-dependent increases in cocaine-appropriate responding and fully substituted for cocaine. Cocaine methiodide, a charged, quaternary cocaine analog, did not substitute for cocaine. Neither pentobarbital, haloperidol nor SCH 23390 produced cocaine-like behavioral activity. Both D1- and D2-selective agonists with diverse structures partially substituted for cocaine, producing from 40 to 80% cocaine-appropriate responses. The D1 agonists studied were SKF 38393 and stereoisomers, SKF 75670 and CY 208-243. Dihydrexidine, a full D1 agonist for induction of adenylate cyclase activity, also only partially substituted for cocaine. The peripherally acting D1 agonist, fenoldopam, produced predominantly saline-appropriate responding that was unrelated to dose. The D2 agonists tested were pergolide, quinpirole, (-)-NPA, RU 24213, N-0434 and N-0437. The D2 antagonist haloperidol did not block the discriminative stimulus effects of cocaine. In contrast, the D1 antagonist SCH 23390 reduced the discriminative stimulus effects of cocaine by a maximum of 50%. These results suggest that both D1 and D2 receptors may play a role in the discriminative stimulus effects of cocaine but that stimulation of either dopamine receptor subtype alone is not sufficient.

Animals

Evaluations of continuing medical education for chronic obstructive pulmonary diseases.

A continuing medical education program which linked primary care physicians to a source of needed appropriate clinical knowledge at a relatively low cost has been demonstrated. Chronic obstructive pulmonary disease was identified as the health problem; the reference patient population was comprised of coal miner health fund beneficiaries living in a 10-county region. Primary care physicians treating beneficiaries in this region were the eligible program participants. Content of the program was based on multiple sources of information about actual practice needs. Several educational techniques were used in combination to convey the knowledge identified as appropriate in the diagnostic stage. A quasi-experimental program evaluation indicated significant changes in physician knowledge, judgment, and self-reported behavior related to diagnosis and treatment of chronic obstructive pulmonary disease.

Adult

Collateral ventilation.

Ventilation may bypass obstructed airways through collateral channels, including interalveolar pores of Kohn, bronchiole-alveolar communications of Lambert, and interbronchiolar pathways of Martin. Resistance through these channels, like resistance through small airways, increases with decreasing lung volume and with hypocapnia. But whereas the distention of collateral channels and small airways by a variety of factors is similar, the efficiency of ventilation through collateral channels is less than the efficiency through airways. Gas inspired through collateral channels is contaminated with alveolar gas from surrounding lung so that the dead space for collateral ventilation is increased. When one part of the lung ventilates out of phase with the surrounding lung, pulmonary interdependence promotes more homogeneous ventilation. In the presence of airways obstruction, interdependence may be a primary factor governing the rate of collateral ventilation. In man, collateral ventilation is unimportant in normal lungs. However, with disease, it may be critical in producing or compensating for abnormalities. For example, the long time constant for collateral ventilation in the middle lobe may be responsible for atelectasis, which results in the middle lobe syndrome. On the other hand, the short time constant for collateral ventilation in emphysema may be essential for the distribution of ventilation beyond obstructed airways.

Airway Resistance

Objective constructs and cognitive structure.

Some relations between objective content and concrete structure in cognitive systems are examined in repertory grids completed by 58 individuals. Predictions that systems with objective content would show less discrimination, differentiation and integration were unconfirmed, results tending in the opposite direction to that hypothesized. There was a similar outcome for six measures of cognitive style as dependent variables. It it suggested that objective-subjective constructs and their concrete-abstract use should be further investigated with the expectation of finding more complex relations in individuals' cognitive systems.

Adult

Bronchoscopic needle aspiration biopsy of paratracheal tumors.

Primary lung carcinoma adjacent to the trachea and paratracheal nodal metastasis without evidence of the primary tumor or airway invasion require invasive surgical procedures to obtain adequate diagnostic tissues. Adequate diagnostic tissue was obtained in 3 of 5 patients with paratracheal masses by means of a bronchoscopic needle aspiration technique. There were no complications.

Adult

Pulmonary function in young smokers: male-female differences.

To delineate the pattern of pulmonary function abnormalities and associated pathophysiologic mechanisms in young smokers, 205 volunteers between the ages of 18 and 25 were studied with a variety of pulmonary function tests. Differences between male and female smokers were observed. Pulmonary function abnormalities consistent with small airway dysfunction were noted in male smokers, but not in female smokers. Decreased forced expiratory flows at high lung volumes suggesting large airway dysfunction were noted in both male and female smokers. Decreases in diffusing capacity for CO consistent with abnormalities of the pulmonary vascular system were seen in smokers of both sexes, but were more prominent in females. Because men develop chronic obstruction pulmonary disease more frequently than do women even when adjustments for smoking are made, and because women develop primary pulmonary hypertension more frequently than do men, these chronic diseases may reflect distinct pathophysiologic response of the 2 sexes to agents such as cigarettes.

Adolescent