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Biomedical subjects

P Davis

Publications and source records attributed to P Davis.

At least 343 records · Page 19Linked to original sources
PubMed1986

Effect of diclofenac sodium, tolfenamic acid and indomethacin on the production of superoxide induced by N-formyl-methionyl-leucyl-phenylalanine in normal human polymorphonuclear leukocytes.

The effect of three non-steroidal anti-inflammatory drugs, diclofenac, indomethacin and tolfenamic acid, on the production of superoxide (O2-), by normal human polymorphonuclear leukocytes (PMNL) was studied, in vitro. The cells were activated with N-formyl-methionyl-leucyl-phenylalanine (FMLP) and O2- production was measured as superoxide dismutase inhibitable cytochrome c reduction. Cell viability was checked with assays of liberated LDH. Concentrations of the drugs considerably higher than those of therapeutic plasma were required to inhibit O2- production. The drug concentrations producing a 50% inhibition (IC50) of total O2- production were: diclofenac 2.7 X 10(-4) M, indomethacin 4.0 X 10(-4) M and tolfenamic acid 4.2 X 10(-4) M. At drug concentrations causing a significant suppression of O2- generation, diclofenac showed a slight and tolfenamic acid a marked inhibition of [3H]FMLP binding to its cellular receptor; indomethacin has earlier been shown to inhibit FMLP-binding slightly. No dismutating activity of the drugs could be demonstrated. It is concluded that the inhibition of O2- production is due to a combined effect on FMLP binding and on cellular O2- metabolism. Because of the high drug concentrations required to inhibit O2- production, this phenomenon is obviously of little significance for the anti-inflammatory effect obtained with therapeutic doses of the drugs studied.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1986

Effects of gold compounds on leukotriene B4, leukotriene C4 and prostaglandin E2 production by polymorphonuclear leukocytes.

The effects of auranofin (AF) and sodium aurothiomalate (GSTM) on the production of specific arachidonic acid metabolites by chemotactic tripeptide activated polymorphonuclear leukocytes has been investigated using radioimmunoassay techniques. AF insignificantly enhanced the production of leukotrienes B4 and C4 at a concentration of 0.5 microgram Au/ml. However, at increasing concentrations, this drug suppressed the production of these metabolites in a dose dependent manner. In contrast, GSTM did not affect the production of either leukotriene at the concentrations tested. Of particular interest, prostaglandin E2 production was not affected by either gold compound. Both leukotrienes and prostaglandins are metabolized from arachidonic acid and are potent mediators of inflammation. The inhibition of leukotriene production may be another mechanism by which AF manifests its antiinflammatory effects in patients with rheumatoid arthritis.

Adult↗
PubMed1985

Asthma mortality.

Explore the source record for details and available documents.

Adolescent↗
PubMed1985

Distal posterior interosseous nerve syndrome.

Six patients selected from 13 patients presenting with dorsal wrist pain related in onset to repetitive dorsiflexion maneuvers are described. Clinical examination revealed tenderness over the fourth extensor compartment. Wrist dorsiflexion reproduced their symptoms. All patients were relieved by selective bupivacaine (Marcaine) block of the posterior interosseous nerve 3 cm proximal to the wrist joint. Of the 13 patients presenting, seven improved on immobilization and anti-inflammatory drugs. The six patients not relieved underwent surgical exploration with the specific findings of an enlarged, fibrotic, posterior interosseous nerve. Histologic analysis revealed perineural fibrosis without inflammatory changes. The perineural fibrosis was four times greater in affected nerves than in control specimens. We propose distal posterior interosseous nerve syndrome as another entity causing dorsal wrist pain that is distinct from the usual causes, such as dorsal ganglia, degeneration of the scapholunate ligament, and dorsal wrist syndrome.

Adult↗
PubMed1985

A primate model (Macaca mulatta) to study the pharmacokinetics of heparin and its fractions.

We have extensively studied the hemostatic parameters and the responses to the anticoagulant action of heparin and its fractions in the primate model (M. mulatta) and found these to be identical to those obtained in humans. The functional properties of antithrombin III, alpha 2-antiplasmin, and platelet factor 4 were also identical to humans in amidolytic and coagulant assays. Human antibodies against FPA, B beta 15-42 peptide, platelet factor 4, and thromboxane B2 reacted with the primate antigen, and assays were developed to measure these parameters in primates. Infusion of activated prothrombin complex concentrates (more than 100 U/kg/day) on a continual basis up to 3 days resulted in a hypercoagulable state manifested by an elevation of FPA, thromboxane B2, and changes in the thrombelastographic patterns. Similarly, infusion of homologous primate serum also resulted in a hypercoagulable state, as was evident by a sharp increase in the FPA levels. The antithrombotic effects of intravenous and subcutaneous administration of heparin, its low molecular fraction, and their constituents were studied after intravenous and subcutaneous injections. The low molecular weight fractions showed the most effective antithrombotic effects, whereas somewhat milder protection was observed with the starting material and highly anionic fraction. The prolongation of global tests, such as the APTT, TT, and changes in the thromboelastogram did not correlate with the reduction in the blood markers of hypercoagulable state. A modified simplate bleeding time method was used to study the effect of heparin and its fractions on the bleeding profile of heparin fractions. The components of fibrinolytic systems were also measurable in both the clot-based and amidolytic methods to predict the profibrinolytic actions of heparin fractions in its mode. These studies suggest that plasma markers, such as the platelet release proteins, products of thrombin activation, and prostaglandin metabolites, may provide better indices in the monitoring of the antithrombotic actions of newer heparins and antithrombotic drugs. Studies suggest that the pathophysiologic responses after a thrombogenic trigger in the primate model are close to humans, and drug modulation of these may provide relevant clinical information. This model provides the most similar preclinical model to study the actions of heparin fractions.

Animals↗
PubMed1985

The behavioral high-risk paradigm and bipolar affective disorder, VIII: Serum free cortisol in nonpatient cyclothymic subjects selected by the General Behavior Inventory.

The degree of biologic concordance between bipolar affective disorder and cyclothymia was assessed within a 3-hour protocol of cortisol functioning. Cyclothymic subjects, selected by the General Behavior Inventory, showed cortisol hypersecretion approaching that of subjects with major affective disorders; they also showed poor modulation of cortisol levels over time, the degree of which was related to increased current level of depression and to a chronic, intermittent depressive course. These results not only support the validity of the General Behavior Inventory but also suggest that cyclothymic subjects with a chronic depressive course may experience persistent biologic disturbance similar to that found during episodes of major depression.

Adolescent↗
PubMed1985

Alcohol-related impairments in male alcoholics and the psychiatric symptoms of their spouses: an attempt to replicate.

This paper reports two attempts to replicate a recent finding by Steinglass linking social-behavioral consequences of drinking with the nonalcoholic spouse's psychiatric symptomatology. Only weak support was obtained for the original findings. Discussion focused on several variables which appeared to be importantly related to the strength and generalizability of relationships under investigation.

Adult↗