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Biomedical subjects

H Hill

Publications and source records attributed to H Hill.

At least 55 records · Page 3Linked to original sources

Concentration-related effects of morphine on cognition and motor control in human subjects.

Morphine and other opioid analgesics may interfere with normal cognition and motor function when the drugs are used for long-term treatment of pain. We used individually tailored steady-state drug infusions to identify the nature and extent of cognitive and motor effects of the mu-receptor-selective opioid morphine in healthy volunteers. The tailored infusions allowed evaluation of cognitive and motor effects at three sequential, constant plasma concentrations of morphine in each subject. Compared with functional assessments obtained in a separate saline infusion day, infusions of morphine to plasma concentrations in the usual therapeutic range for analgesia caused significant impairments of some but not all elements of cognitive and motor function. The time needed to encode and process serially presented verbal information increased and the ability to maintain low consistent levels of force decreased during the morphine infusion. We also assessed verbal recall 3 hours after the morphine and saline infusions. Delayed recall of information presented during the morphine infusion was significantly impaired. Our results demonstrate that morphine can interfere with cognitive and motor performance at plasma drug concentrations within the usual therapeutic range.

Adult↗

The detection of antibodies to the glycoprotein X antigen of pseudorabies virus.

The persistence of antibodies to glycoprotein X (gpX) in the serum of pigs experimentally infected with pseudorabies virus (PRV) was determined using an anti-gpX enzyme-linked immunosorbent assay (ELISA). Antibodies to gpX were detected for at least 365 days postchallenge in nonvaccinated pigs. Previous sensitization of pigs by vaccination with S/PRV had no apparent effect on the antibody response of pigs to gpX postchallenge. In determining previous exposure of pigs to PRV strains containing the gpX gene, the anti-gpX ELISA was highly specific, but its sensitivity was lower than the standard serological procedures currently used for detecting PRV antibodies.

Animals↗

Comparison of bile porphyrin concentrations in cattle and human beings with protoporphyria.

Blood and bile porphyrin concentrations were measured in cattle with protoporphyria and compared with those in human beings with the disease. Whereas the mean RBC porphyrin concentration in cattle was 18-fold greater than in human beings, the mean bile porphyrin concentration was only 78% greater. Sequential measurements over a 30-hour period in 1 animal with a bile fistula indicated that the ratio of total porphyrin to total bile acid in bile varied minimally. When the animal was given an IV infusion of taurocholate, the biliary excretion rate of porphyrin increased in parallel with that of bile acid, because of enhancement of bile flow. Thus, in cattle with protophorphyria, the concentration of porphyrin in bile is low compared with that of porphyrin in RBC, in contrast with findings in human beings, and adequate amounts of bile acids are secreted to maintain efficient protoporphyrin excretion. This explains, in part, why hepatobiliary disease has not been observed in cattle with protoporphyria, but has been seen in human beings with the disease.

Animals↗

Dose effects of alfentanil in human analgesia.

Alfentanil, a rapidly acting opioid, was given in subanesthetic doses to 10 subjects in a laboratory setting. Analgesia was assessed from the subjects' responses to painful dental stimulation. A subjective pain report (PR) and brain evoked potential (EP) amplitude were obtained repeatedly before and after injection on each of 4 testing days, on which the following intravenous doses were administered: 0 (saline solution), 5, 10, and 15 micrograms/kg. Significant dose effects were observed for EP amplitude during but not beyond the distributional t1/2 of the drug, but significant effects on the PR extended beyond this time point. Mean volume of distribution, total body clearance, and distribution t1/2 did not differ significantly across the doses of alfentanil. Strong correlations between each effect measure and plasma drug concentration were observed at all doses and were significant at P less than 0.01. The EP scores tracked the distribution of alfentanil very closely, but the correlation between EP amplitude and plasma alfentanil concentration was lower during the elimination phase. In contrast, the PR effects closely tracked the elimination of alfentanil but not its distribution. These findings suggest that EP amplitude and the PR represent two different central effects in opioid analgesia.

Adult↗

The role of prostaglandins in cercarial (Schistosoma mansoni) response to free fatty acids.

In examining the structure-activity relationship of a diverse group of chemicals reported to prevent cercarial penetration after topical application, we noticed a moiety that was common to free fatty acids and prostaglandins. Because unsaturated fatty acids have been reported to stimulate cercarial penetration, we hypothesized that cercarial stimulation by skin and fatty acids may invoke prostaglandin mechanisms in cercariae, skin, or both. Thus we compared the stimulation of cercariae by a series of essential and nonessential fatty acids and demonstrated an inhibition of this response by ibuprofen and aspirin, known cyclo-oxygenase inhibitors, and by 13-azaprostanoic acid, a potent antagonist of the thromboxane/endoperoxide receptor. These data led us to postulate a major role for prostaglandins in the cercarial penetration response.

Animals↗

EPA health and environmental effects data analysis system.

This paper discusses the development of a system to organize, store, retrieve, and correlate data pertaining to chemicals and their biological and environmental effects. The particular problems of data identification, acquisition, classification, and automation are discussed in relation to existing data sources and methods of data collection and analysis. The problems of computer software development are also addressed, and a design overview of the system is presented.

Animals↗

Resumption of treatment with penicillamine after proteinuria.

Penicillamine has been successfully reintroduced and continued for a minimum of 13 months in 5 patients who developed proteinuria during the first course of the drug. The daily maintenance dose during the second course was 150--250 mg taken midway between 2 meals. Proteinuria did not recur; no significant excretion of fibrin degradation products occurred; complement, urea, creatinine, and serum albumin remained within normal limits. Urine microscopy showed no abnormality.

Arthritis, Rheumatoid↗

On the significance of the increase in homovanillic acid (HVA) caused by antipsychotic drugs in corpus striatum and limbic forebrain.

The effect of various antipsychotic drugs on the blockade of dopaminergic receptors in striatum and limbic forebrain was examined by establishing dose-response curves for the increase in HVA and for the antagonism of d-amphetamine-induced rotation in rats with unilateral lesions of the substantia nigra. A good quantitative correlation was found between dopaminergic blockade in the striatum as reflected by the ED100 for striatal HVA increase and the ED50 for rotational antagonism and the occurrence of extrapyramidal side effects in man. The ED100 for the increase in HVA in the limbic forebrain showed the same rank order of potency as those in the striatum: Haloperidol greater than primozide greater than chlorpromazine greater than thioridazine greater than clozapine. The results thus demonstrate a very good correlation between the degree of dopaminergic blockade and the increase of extrapyramidal side effects in man, but suggest the possibility of a dissociation between dopaminergic blockade and antipsychotic activity.

Animals↗