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Biomedical subjects

P Terry

Publications and source records attributed to P Terry.

At least 19 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

The effect of unilateral anteromedial cortex lesions on prey-catching and spatio-motor behaviour in the rat.

The neglect which follows a unilateral lesion of anteromedial cortex in rat was examined using two tasks. In the first task animals had to press the left bar of a two-bar Skinner box for food reward. In the second task animals captured live locusts presented in either their right or left visual field. The results showed that in the Skinner box there was a transitory spatial neglect contralateral to the lesion, which disappeared after 2-3 days. In the prey-catching task animals failed to target or track locusts when they were in the field contralateral to the lesion throughout the 4-day testing period. Capture and consummatory responses were normal when the locust was presented (or moved independently) into the ipsilateral (non-neglected) field. 60 days later the asymmetrical response to locusts in the contralateral field had disappeared.

Animals

Effects of propranolol on, and noradrenergic correlates of, the response to nonreward.

Rats were rewarded by food for running in a straight runway with short (15 sec) intertrial intervals. On the final day, animals were subjected to either 14 extinction trials or 14 rewarded trials. During acquisition, half of each group had been injected once daily for 15 days with propranolol (5 mg/kg IP), the remainder with saline vehicle. All animals were killed immediately after the final trial and the cerebral cortex taken for noradrenaline assay and radioligand binding to beta- and alpha 2-adrenoceptors. Propranolol increased running times early in extinction; this effect was replicated in a second experiment. Neither the drug injections nor the extinction procedure affected neurochemical measures. However, the rate of extinction correlated positively with both beta- and alpha 2-adrenoceptor number. Although consistent with the theory that beta-adrenoceptors are involved in adaptation to stress, these results differ from our previous findings. The relationship between beta-adrenoceptor number and the response to stress may depend on the severity of the stress.

Animals

Acute and chronic effects of propranolol on extinction of rewarded running in the rat.

Three experiments examined the effect of propranolol injected IP on a series of 16 extinction trials at 24-hour intertrial intervals after continuously rewarded running. In Experiment I, propranolol (1, 5 or 10 mg/kg) was injected, in different groups, shortly before or shortly after each extinction trial, but without effect. In Experiment II, the same doses were injected daily for 18 days preceding extinction, to allow longer for any long-term drug effect to accumulate. Propranolol (1 mg/kg) facilitated extinction. In Experiment III, a single dose (7.5 mg/kg) was injected before or after extinction trials as in Experiment I; the acute effect was to impair extinction. These results are consistent with previous findings in the Skinner box that propranolol has an acute disinhibitory effect on nonrewarded responses and a long-term inhibitory one. These effects have different dose-response relationships.

Animals

An update on HIV-testing at a London sexually transmitted diseases clinic: long-term impact of the AIDS media campaigns.

Trends in the number of tests for HIV-1 antibody at a London sexually transmitted diseases clinic showed substantial changes between September 1985 and June 1988. From an average of 100 tests per month between September 1985 and August 1986, the average increased to 365 tests per month for September 1986 to August 1987. This levelled off at 243 tests per month between September 1987 and June 1988. The average number of positive tests per month between September 1985 and June 1988 remained constant, though the number of seropositive tests in females increased. Male and female populations displayed similar temporal patterns. The greatest increase was seen in the tests generated by heterosexual males and females with no other risk factors. This group generated 42% of the 8012 tests performed during the study period. The Clinic's catchment area predominantly included London and surrounding areas and temporal patterns were similar for residents from each of the Thames Regions. The temporal patterns observed coincided with periods of increased media attention on HIV infection/AIDS and involved campaigns by the popular press, television, Department of Health Education Authority. The increase in tests during the time of maximum media exposure, the subsequent plateau at a level substantially higher compared with the period preceding the media campaigns and the large increase in heterosexual males and females tested, all suggest that the campaigns have contributed to increasing awareness of HIV infection/AIDS as a major contemporary public health problem.

AIDS Serodiagnosis

Anomalous patterns of response learning and transfer in decorticate rats.

Behavioural flexibility in decorticate rats was examined by testing response transfer in an obstructed alleyway. In the first experiment, rats were trained to push a ball out of a cylindrical alleyway in order to gain access to the goal box. When this 'push' habit was prevented by blocking forward movement of the ball, decorticate rats were much quicker than sham-operated rats in successfully developing the novel clearance response of pulling the ball into the start box. Both groups were subsequently able to reverse effectively between responses. In a second experiment, sham-operated and decorticate rats were first shaped to pull the ball clear from the alleyway, and then required to adopt a push-type clearance response when movement of the ball towards the start box was prevented. Here, the decorticates showed difficulty both in learning to pull the ball out of the alley and in transferring to a push-type clearance response, but having transferred they coped well with subsequent reversals. This asymmetrical pattern of transfer results is not readily attributed to response preference and raises the possibility that, in some situations at least, decorticated animals may show greater behavioural flexibility than had previously been supposed.

Animals

Computer analysis, using a digitizer, of ataxic mouse gait due to drugs.

A simple objective method using the irregularity of the spacing of rats' footprints to determine drug-induced locomotor ataxia has been adapted for mice and for computer analysis, by means of a digitizer-based program. Results obtained by the usual manual method of measuring and analyzing the records are compared with results of the computerized method. The computer method improves speed, and perhaps accuracy, of measurement and analysis, especially with large numbers of records, although manual scoring gives satisfactory results and remains essential for unusual records. Inter-observer agreement of the computerized method was high, and there was good agreement between measurements and subjective ratings of ataxia. The use of footprints to measure ataxia, with or without computer aid, is recommended as a routine test in laboratory evaluation of psychoactive drugs. Other uses discussed include determining changes in different characteristics of gait such as step width and step length in animal and human subjects affected not only by drugs, but also by movement disorders such as Parkinsonism.

Amobarbital

Risk factors for HIV-1 infection in a British population: lessons from a London sexually transmitted diseases clinic.

Between September 1985 and June 1988, 6923 people (4550 men and 2373 women) were tested for HIV-1 antibodies at a sexually transmitted disease clinic, London, UK. Of the 6923 individuals tested, 558 (8%) were seropositive, of whom 523 (94%) were men and 35 (6%) women. Of the seropositives, 84% were homosexual or bisexual men, 5% were intravenous drug users, 4% were heterosexual contacts of HIV seropositives, 4% had multiple risk factors, 2% were heterosexual contacts of central African partners and 1% were heterosexuals with no other risk factors. This prevalence pattern conforms to that observed in other industrialized nations. For the women, heterosexual intercourse with an HIV-infected partner, intravenous drug use and heterosexual contact with a partner from central Africa were the main risk factors for infection. The important risk factors among the men were heterosexual contact with an HIV-seropositive partner, being homosexual or bisexual, intravenous drug use and heterosexual contact with a resident from central Africa. heterosexual and homosexual transmission were implicated as the main routes for viral spread in this British population.

Acquired Immunodeficiency Syndrome