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Biomedical subjects

A Hume

Publications and source records attributed to A Hume.

12 recordsLinked to original sources

Behavioral and neurochemical effects of continuous infusion of cocaine in rats.

The ability of continuous intravenous infusion of cocaine (60 mg/kg per day for 11 or 12 days; by osmotic minipump) to alter responses to acute injection of cocaine (20 mg/kg, i.p.; given 24 hr after termination of the infusion by minipump) was tested in conscious, tethered Sprague-Dawley rats. Extracellular levels of cocaine, dopamine and metabolites of dopamine in the striatum were determined by in vivo microdialysis. Locomotor activity and stereotyped behavior were evaluated simultaneously during dialysis sampling. Prior infusion of cocaine blunted the ability of acute challenge with cocaine to increase the efflux of dopamine in the striatum, locomotor activity and stereotypy. Increases in extracellular levels of homovanillic acid in the striatum were significantly greater in cocaine-infused rats than vehicle-infused controls, both prior to and after acute injections of cocaine. However, no differences between these two groups were observed in levels of cocaine in the striatum after acute challenge. Extracellular levels of dopamine in the striatum correlated significantly (P less than 0.05) with stereotypy in both groups but with locomotor activity only in cocaine-infused rats. The results indicate that behavioral tolerance occurred after continuous intravenous infusions of cocaine, that this was correlated with neurochemical tolerance to acute cocaine challenge and that alterations in the metabolism of cocaine did not account for the observed behavioral responses.

3,4-Dihydroxyphenylacetic Acid

Cocaine elevates striatal dopamine efflux in spontaneously hypertensive and Wistar-Kyoto rats.

The effects of acute cocaine administration on central dopaminergic systems were examined in the striata of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats with the use of an in vivo microdialysis technique. Increased extracellular levels of dopamine were observed for 45 to 75 minutes following acute cocaine administration in both halothane-anesthetized and conscious SHR and WKY. However, no significant differences were noted between anesthetized and conscious SHR and WKY in either baseline levels or cocaine-induced changes in extracellular levels of dopamine and its metabolites. A positive, linear correlation between extracellular levels of dopamine and cocaine was demonstrated for the 60-min period following acute cocaine administration in both SHR and WKY. The slopes of the linear regression plots obtained from the data of each 15-min sample was slightly, but significantly, higher in conscious SHR than in conscious WKY. The present results suggest a transient and dose-related stimulation of striatal dopamine release following acute cocaine administration and a linear relationship between striatal extracellular levels of dopamine and cocaine in both SHR and WKY.

3,4-Dihydroxyphenylacetic Acid

MCMI differences between alcoholics and cocaine abusers: effect of age, sex, and race.

Samples of alcohol-dependent-only subjects (n = 164), cocaine-dependent-only subjects (n = 63), and subjects dependent on multiple substances, including alcohol and cocaine (n = 103), were administered the Millon Clinical Multiaxial Inventory (MCMI) as part of a routine clinical evaluation. The alcohol-only group was older (M = 38.7 years) and had a higher percentage of White subjects than other groups. The multiple-use (60%) group also had a higher percentage of White subjects than the cocaine only group (38%) and a higher percentage of male subjects (81%) than the alcohol-only group (67%). Although the MCMI characteristics of each diagnostic group paralleled previous findings, few MCMI differences were found after controlling for age, sex, and race effects. The implications of these results for treatment development are discussed.

Adult

Personality characteristics of alcohol dependent inpatients: relationship of MCMI subtypes to self-reported drinking behavior.

Recent cluster analytic research with alcoholic inpatients has demonstrated the existence of several Millon Clinical Multiaxial Inventory (MCMI) clusters that appear to be consistent across different subject samples. The validity of these data would be strengthened by a statistical demonstration of the similarity of attained clusters across studies--a demonstration of concordance of subject classification across different clustering techniques on the same data set- and the inclusion of external, independent measures against which to evaluate the predictive validity of the cluster typology. We found a high level of concordance in subject classification across different clustering methods on the same data set and a high level of agreement with cluster typologies attained in previous studies. Subsequent multivariate analyses employing independent scales measuring various aspects of alcohol use confirmed differences among cluster members on perceived benefits of alcohol use and deleterious effects of alcohol use. The prominent differences in alcohol use along with a rationale for their development are discussed.

Adolescent

The acute effects of cigarette smoking on cutaneous blood flow in smoking and non-smoking subjects with and without Raynaud's phenomenon.

The acute effects of smoking a single cigarette on peripheral blood flow were investigated by laser-Doppler flowmetry in nine patients with Raynaud's phenomenon and 12 normal controls. In regular smokers, a marked fall in finger blood flow was demonstrated, but this was not present in non- or irregular smokers. In addition, no effect on capillary blood flow was found. There was no difference between subjects with and without Raynaud's phenomenon. In five normal, non-smoking volunteers, 2.4 g of aspirin for 3 days resulted in a similar fall in blood flow due to a single cigarette. These results suggest that regular smoking sensitizes the peripheral vasculature to the vasoconstricting effects of the next cigarette, and that at least part of this sensitization is mediated by the inhibition of endothelial prostacyclin synthesis. Patients with Raynaud's phenomenon, either primary or secondary, are no more sensitive than normal subjects, but should nevertheless avoid cigarette smoking.

Adult

C4a anaphylatoxin levels as an indicator of disease activity in systemic lupus erythematosus.

The use of a synthetic protease inhibitor, nafamstat mesilate, has enabled reliable estimations of in vivo complement activation to be made in systemic lupus erythematosus (SLE). Elevation of C3a anaphylatoxins was found in two out of 24 patients and elevation of C4a anaphylatoxins was found in 20 out of 24 patients, confirming that complement activation, predominantly by the classical pathway, is a common occurrence in the disease. Significantly higher levels of C4a anaphylatoxin were found in 16 patients, with more aggressive disease requiring supplementary treatment with azathioprine, while the remaining eight patients, with less severe disease, required purely steroid therapy. Very strong associations between elevated C4a anaphylatoxins and raised DNA antibody titres, C1q binding activity and low complement C4 levels were also observed, suggesting that anaphylatoxin measurement may be a sensitive additional method for monitoring disease activity in SLE.

Adult

Complement activation in systemic sclerosis.

The use of a synthetic protease inhibitor, nafamstat mesilate, has enabled reliable estimations of in vivo complement activation to be made in patients with systemic sclerosis. Elevations of C3a and C4a anaphylatoxins were found in 2 and 24 out of 30 patients respectively, indicating that complement activation, predominantly by the classical pathway, is a common occurrence in the disease, even though complement C3 and C4 levels were within the reference range.

Adult

Antibody-dependent cellular cytotoxicity of vascular endothelium: characterization and pathogenic associations in systemic sclerosis.

Ten sera from 48 patients with systemic sclerosis were found to be capable of producing cytotoxicity of human umbilical venous and arterial endothelium when co-cultured with peripheral blood mononuclear cells. Fractionation of sera on Ultrogel and the preparation of monomeric IgG by ion exchange and affinity chromatography suggested that the cytotoxicity was mediated by anti-endothelial antibodies capable of pre-sensitizing target cells in a mechanism that resembled antibody-dependent cellular cytotoxicity. These anti-endothelial antibodies together with C1q-binding immune complexes and anti-cardiolipin antibodies were found in 18 of 28 patients so investigated, suggesting that multiple immunological mechanisms may be involved in the pathogenesis of the vascular lesion of systemic sclerosis.

Antibody-Dependent Cell Cytotoxicity

Reactive hyperemic responses in systemic sclerosis patients and healthy controls.

Hyperemic responses after arterial occlusion were investigated in patients with Raynaud's phenomenon due to systemic sclerosis (SSc) and in healthy controls. The hyperemia due to arterial occlusion for 2 min was measured by laser-Doppler flowmetry. If the hyperemic response was absent, the measurements were repeated after vasodilatation was induced by hand warming in warm water. Reactive hyperemia was absent in 12 patients when investigations were performed on the unwarmed hand, and these patients had very low resting blood flows. After vasodilatation was induced in these patients, and also in those patients whose resting blood flow was normal, hyperemic responses were comparable in magnitude with those in the controls. The slope of the hyperemic response was significantly less in the patients (1.11 +/- 0.02 V/s) than in the controls (1.28 +/- 0.03 V/s), and therefore, the time course of the hyperemia was lengthened in the patients with SSc, with a delay to achieving maximum blood flow of 2 min. Peak blood flow was directly related to the level of the initial blood flow. These findings support the view that reactive hyperemia is principally a mechanical phenomenon, and also that vessel wall reactivity is abnormal in SSc, producing delayed hyperemic responses. The magnitude of the hyperemia depends on initial flow rates, and the apparent lack of these responses in SSc is a result of their low, but reversible, resting blood flow.

Constriction

The effect of simple warming procedures on finger blood flow in systemic sclerosis.

Finger blood flow was measured by laser Doppler flowmetry in 15 patients with Raynaud's phenomenon (RP) due to systemic sclerosis (SS), and 15 normal controls. Measurements were performed in a temperature controlled room at 28 degrees C. The blood flow in the patients was significantly lower than in the controls (P less than 0.001). After hand warming in water at 35 degrees C for 10 min, blood flow in the patients and controls did not differ significantly. Following this, the response to a standardized cold stress produced similar falls in both groups to levels that were not significantly different and these occurred over a similar time course. After cold stress ended, there was recovery of blood flow in both groups, and blood flow after 20 min was not significantly different between the two groups. The induced vasodilatation persisted, in those patients in whom it was remeasured, for at least 2 h. Repeating the experiments at a room temperature of 24 degrees C produced similar results. This indicates that considerable vasodilatation is possible in these patients, and can be produced by simple means. It also indicates that local and central thermoregulatory reflexes are intact. Cold induced symptoms in patients with SS are related to low resting blood flow, not to cold sensitivity, and simple warming may provide a useful treatment.

Adult

Anticardiolipin antibodies in systemic sclerosis: immunological and clinical associations.

Anticardiolipin antibodies of IgG/IgM class were detected in seven of 28 patients with systemic sclerosis including five of 16 patients severely affected by extensive visceral disease. This severely affected sub-group also showed significant elevations of plasma levels of von Willebrand factor antigen in 10 cases and serum C1q binding activity in seven cases respectively. This triple association raises the possibility that multiple immunological mechanisms are involved in the pathogenesis of systemic sclerosis and its vascular lesions.

Adult

The value of embryo transfer to cattle breeding in Britain.

An analysis is made of the maximum expenditure which could be justified in embryo transfer in cattle is used to: increase the rate of genetic improvement of dairy or beef cattle; increase the frequency of twin-pregnancies; and expedite a change of breed. Estimates of maximum justifiable expenditure have been compared with an estimate of the cost of non-surgical transfer. Embryo transfer should be used in elite beef herds to increase selection intensity, particularly if bulls from such herds can be used for artificial insemination. Other commercial applications will not be economically justifiable until the cost of transfer has fallen by 50 to 80 per cent.

Animals