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Biomedical subjects

D Stanton

Publications and source records attributed to D Stanton.

17 recordsLinked to original sources

Comparative effects of antiglaucoma drugs on voltage-dependent calcium channels.

BACKGROUND: Experimental evidence suggests that substances able to interact with voltage-dependent Ca2+ channels (VDCCs) might be beneficial in glaucoma management. It was therefore of significance to show that beta-adrenoceptor antagonists used in glaucoma directly interact with L-type VDCCs. In the present study, the affinity of several antiglaucoma drugs (betaxolol, carteolol, levobunolol, timolol, brimonidine, dorzolamide, latanoprost and pilocarpine) for these and other VDCCs was investigated using radioligand binding assays. Experiments were also carried out to assess the effect of antiglaucoma drugs on the NMDA-stimulated Ca2+ influx into isolated rat retinas. METHODS: Competition radioligand binding studies to L-, N- and P/Q-type VDCCs were performed in rat cortical homogenates. The effects of antiglaucoma drugs on the NMDA-stimulated influx of 45Ca2+ were studied in isolated rat retinas. RESULTS: Only beta-adrenoceptor antagonists significantly interacted with radioligand binding to L-type VDCCs, with betaxolol displaying the highest potency. None of the antiglaucoma drugs tested showed any significant affinity for either N- or P/Q-type VDCCs. Only beta-adrenoceptor antagonists attenuated the NMDA-stimulated 45Ca2+ influx into isolated rat retinas, with betaxolol exhibiting at least 10 times higher potency than timolol. Brimonidine, dorzolamide, latanoprost and pilocarpine did not elicit any significant effect on the NMDA-stimulated 45Ca2+ influx. Additional experiments strongly suggested that the effect of betaxolol on the NMDA-stimulated 45Ca2+ resulted from inhibition of L-type VDCCs. CONCLUSION: Of the antiglaucoma drugs investigated, betaxolol displays the greatest L-type VDCC-blocking activity and this may be of clinical relevance. Such a characteristic could account for some of its described ocular actions.

Adrenergic beta-Antagonists↗

Behavioral and biologic evidence of persistent high-risk behavior in an HIV primary care population.

OBJECTIVE: To define the prevalence of gonorrhea, chlamydial infection, and high-risk sexual behavior in an HIV primary care clinic. DESIGN: Subjects enrolling in this cross-sectional study answered a brief interviewer-administered questionnaire and provided a urine sample for gonorrhea and chlamydia testing. SETTING: A large urban HIV primary care clinic. PARTICIPANTS: HIV-infected patients presenting for a scheduled medical visit from June 1997 to April 1998. MAIN OUTCOME MEASURES: Prevalence of self-reported high-risk sexual behavior and gonorrhea and chlamydial infection. RESULTS: Of 691 patients consenting to the study over a 10-month period, 58% reported sexual activity in the past 90 days, 7.4% reported multiple sexual partners in the past month, and 34.6% did not use a condom at last sexual encounter. Overall, 4.6% reported a history of either gonorrhea or a chlamydial infection in the past year. Of 637 giving a urine sample for testing, the prevalence of chlamydial infection was 2.4%; the prevalence of gonorrhea was 1.6%. Overall, 7.5% of those screened had either current or recent (within 1 year) gonorrhea or chlamydial infection. Current or recent gonorrhea or chlamydial infection was not associated with age, gender, HIV transmission risk, CD4 cell count, HIV viral load, symptoms, or self-reported risk behavior. CONCLUSION: High-risk sexual behavior and unrecognized sexually transmitted diseases (STD) are common among HIV-infected persons followed in primary medical care. Enhanced detection of treatable STD among this population coupled with improved risk-reduction counselling may be important clinical practice measures that can curb the spread of HIV.

Adult↗

Dual displays.

The study examined whether the simultaneous presentation of different map displays can aid situational awareness in spatial tasks relying on ego-centred and world-centred reference frames. Two commonly used aircraft displays, track-up and north-up maps, were compared with a dual aircraft display consisting of both track-up and north-up maps. Participants took part in two tasks: one relied on an ego-centred reference frame (ERF) and the other on a world-centred reference frame (WRF). The ERF task involved left/right judgements with respect to the aircraft's current heading while in the WRF task participants were asked to identify the compass heading associated with a landmark. A moderate amount of training resulted in a significant improvement with the dual maps in both the WRF task (relative to track-up maps) and the ERF task (relative to north-up maps). The findings are discussed with reference to how attention is allocated to visual displays.

Adolescent↗

A rejoinder.

Explore the source record for details and available documents.

Persons with Disabilities↗

Uses of virtual reality in clinical training: developing the spatial skills of children with mobility impairments.

In this chapter we review some of the ways in which the skills learned in virtual environments (VEs) transfer to real situations, and in particular how information about the spatial layouts of virtual buildings acquired from the exploration of three-dimensional computer-simulations transfers to their real equivalents. Four experiments are briefly described which examined VR use by disabled children. We conclude that spatial information of the kind required for navigation transfers effectively from virtual to real situations. Spatial skills in disabled children showed progressive improvement with repeated exploration of virtual environments. The results are discussed in relation to the potential future benefits of VR in special needs education and training.

Computer Simulation↗

Virtual reality, disability and rehabilitation.

Virtual reality, or virtual environment computer technology, generates simulated objects and events with which people can interact. Existing and potential applications for this technology in the field of disability and rehabilitation are discussed. The main benefits identified for disabled people are that they can engage in a range of activities in a simulator relatively free from the limitations imposed by their disability, and they can do so in safety. Evidence that the knowledge and skills acquired by disabled individuals in simulated environments can transfer to the real world is presented. In particular, spatial information and life skills learned in a virtual environment have been shown to transfer to the real world. Applications for visually impaired people are discussed, and the potential for medical interventions and the assessment and treatment of neurological damage are considered. Finally some current limitations of the technology, and ethical concerns in relation to disability, are discussed.

Activities of Daily Living↗

Deducing the pattern of arthropod phylogeny from mitochondrial DNA rearrangements.

The origins of arthropods and the phylogenetic relationships among their three major living groups (atelocerates, crustaceans and chelicerates) are vigorously contended. To help resolve this, we determined mitochondrial gene arrangements for a chelicerate, a myriapod, two crustaceans, an onychophoran, a mollusc and an annelid, and compared them with published gene orders of other species. The result strongly supports the monophyly of Arthropoda and of Mandibulata (atelocerates plus crustaceans) and refutes the Uniramia (atelocerates plus onychophorans). Gene arrangement comparisons are emerging as a powerful new tool for resolving ancient phylogenetic relationships.

Animals↗

Racial differences in the use of drug therapy for HIV disease in an urban community.

BACKGROUND: Guidelines for drug therapy in human immunodeficiency virus (HIV) disease are based primarily on the stage of the disease. To determine whether sociodemographic characteristics of patients influence drug therapy in practice, we analyzed the use of antiretroviral therapy and prophylactic therapy for Pneumocystis carinii pneumonia (PCP) in an urban population infected with HIV. METHODS: All patients presenting for the first time to our HIV clinic from March 1990 through December 1992 were enrolled. Data on sociodemographic and clinical variables and on drug use were collected at the time of presentation and after six months. We asked whether patients with CD4+ cell counts of 500 or less per cubic millimeter were receiving antiretroviral therapy at the time of presentation, and whether patients with CD4+ cell counts of 200 or less per cubic millimeter were receiving PCP prophylaxis. RESULTS: Among the 838 patients enrolled, 656 (79 percent) were blacks, 167 (20 percent) were non-Hispanic whites, and 15 (2 percent) were Asian or Hispanic descent or were not racially classified. There were no racial differences in the stage of HIV disease at the time of presentation. However, there were racial disparities in the receipt of antiretroviral therapy: 63 percent of eligible whites but only 48 percent of eligible blacks received such therapy (P = 0.003). PCP prophylaxis was received by 82 percent of eligible whites but only 58 percent of eligible blacks (P < 0.001). There were no significant differences in the receipt of drug therapy with respect to age, sex, mode of HIV transmission, type of insurance, income, education, or place of residence. In a logistic-regression analysis, race was the feature most strongly associated with the receipt of drug therapy. When blacks were compared with whites, the adjusted relative odds were 0.59 (95 percent confidence interval, 0.38 to 0.93) for the receipt of an antiretroviral agent and 0.27 (95 percent confidence interval, 0.13 to 0.56) for the receipt of PCP prophylaxis. CONCLUSIONS: Among patients infected with HIV, blacks were significantly less likely than whites to have received antiretroviral therapy or PCP prophylaxis when they were first referred to an HIV clinic. This disparity suggests a need for culturally specific interventions to ensure uniform access to care, including drug therapy, and uniform standards of care.

AIDS-Related Opportunistic Infections↗

Depolymerization of heparin by complexed ferrous ions.

Treatment of porcine heparin with the ferrous-EDTA complex and ascorbic acid for 24 h at 37 degrees C results in the degradation of most of the glycosaminoglycan to smaller fragments. About 65% of the products comprise oligosaccharides composed of less than 30 sugar units. The extent of depolymerization is decreased significantly if ascorbate or EDTA is not included in the reaction mixture. Gel filtration of the reaction products yielded fractions with narrow chain length ranges. The sulfate content of the fractions and their electrophoretic mobilities on cellulose acetate indicate that the components have equivalent charge densities. Depolymerization products with 20 or more sugar units retain significant anticoagulant potencies as measured by their effect in accelerating the neutralization of factor Xa by antithrombin.

Animals↗

Diagnostic accuracy of three clinical case definitions for advanced HIV disease.

OBJECTIVE: To assess the accuracy of three clinical case definitions for advanced HIV disease: the World Health Organization (WHO) case definition, and the original and revised Caracas case definitions. DESIGN: Retrospective chart review. SETTING: A clinic for patients with all stages of HIV infection at the Johns Hopkins Hospital, Baltimore, [correction of Bethesda] Maryland, USA, a tertiary care university hospital. PATIENTS, PARTICIPANTS: Two hundred and twenty-four HIV-positive adults who underwent initial evaluation between 1 January 1990 and 31 December 1990. MAIN OUTCOME MEASURES: A score for each definition was assigned based on initial evaluation. The sensitivity, specificity, and predictive values were calculated using the Centers for Disease Control (CDC) staging criteria, and results were correlated with total CD4 cell counts. RESULTS: The sensitivities of the WHO, and the original and revised Caracas definitions were 40, 67, and 60%, respectively, using CDC disease stage IV as a positive standard. Specificities were between 99 and 100%, using CDC stage II-III disease as a negative standard. Mean CD4 cell counts for patients with positive scores were 184, 160, and 158 x 10(6)/l, respectively, compared to 191 x 10(6)/l for CDC stage IV patients. Sensitivity was lower when the positive standard was expanded to include all patients with CD4 cell counts less than 200 x 10(6)/l. CONCLUSIONS: In our study population, case definitions were specific, but only moderately sensitive for advanced HIV disease. Prospective studies should be conducted in diverse geographic regions, using lymphocyte or CD4 cell counts when possible.

Acquired Immunodeficiency Syndrome↗

Protection by cysteine esters against chemically induced pulmonary oedema.

Perfluoroisobutene (PFIB) is a hydrophobic reactive gas produced by the pyrolysis of polytetrafluoroethane which induces pulmonary oedema similar to that induced by phosgene when inhaled. When a lethal dose is inhaled by Porton strain rats total non-protein thiol (NPSH) and glutathione (GSH) in the lung are reduced by between 30 and 49%, respectively. If the endogenous levels of thiols in the lung are reduced by pretreatment with buthionine sulfoximine (BSO) 16 hr before exposure to PFIB, the rats become more susceptible to the effects of the gas. The effect of BSO pretreatment on toxicity was prevented by pretreatment 30 min before exposure, with 5 mmol/kg N-acetylcysteine (NAc). NAc increased the levels of cysteine (CySH) in the lung by 150% and GSH was unaffected. Similarly pretreatment with 3 mmol/kg CySH also protected against toxicity and raised CySH levels by 100%. A series of cysteine esters and cystine dimethyl ester (CDME) have been synthesised which selectively raise lung levels of CySH in the rat lungs after intraperitoneal (i.p.) injection. The methyl ester and CDME raised lung levels of CySH by 4000 and 2000%, respectively, 10 min after i.p. injection whilst GSH levels remained unchanged. Cysteine isopropyl ester raised lung levels of CySH by 10,600% but liver levels by only 1400%. All esters except the t-butyl ester (CTBE) also raised maximal plasma levels of NPSH by up to 500%; however, when NAc was injected plasma levels increased by over 1500%. Rats treated with these esters at 3 mmol/kg and with NAc at 5 mmol/kg were protected against lethal doses of PFIB in all cases except when CTBE was used. It appears that these cysteine esters may distribute preferentially into the lung, unlike NAc. The selective enhancement of pulmonary CySH levels may provide a method for the protection of lungs against inhaled reactive toxicants by increasing intracellular CySH. Levels of CySH may also be raised in epithelial lining fluid thus reducing access of gaseous toxicants to pulmonary tissue.

Acetylcysteine↗