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Biomedical subjects

M Poullis

Publications and source records attributed to M Poullis.

At least 19 recordsLinked to original sources
PubMed2001

Concomitant thymectomy and cardiac operation in a patient with pure red cell aplasia.

Pure red cell aplasia is a rare condition resulting in severe anemia. Medical therapy is indicated, unless a thymoma is present. In patients with concurrent cardiac pathology requiring operation, simultaneous operation should be contemplated to avoid risky resternotomy. We describe an exceptionally rare case of a patient with pure red cell aplasia secondary to a thymoma who underwent concomitant thymectomy and coronary artery grafting with a successful surgical outcome.

Combined Modality Therapy↗
PubMed2001

The antithrombotic and antiinflammatory mechanisms of action of aprotinin.

Aprotinin (Trasylol) is generally regarded to be an effective hemostatic agent that prevents blood loss and preserves platelet function during cardiac surgery procedures requiring cardiopulmonary bypass (CBP). However, its clinical use has been limited by the concern that such a potent hemostatic agent might be prothrombotic, particularly in relation to coronary vein graft occlusion. In this review we present a mechanism of action that challenges such a viewpoint and explains how aprotinin can be simultaneously hemostatic and antithrombotic. Aprotinin achieves these two apparently disparate properties by selectively blocking the proteolytically activated thrombin receptor on platelets, the protease-activated receptor 1 (PAR1), while leaving other mechanisms of platelet aggregation unaffected. We also review recent research leading to the discovery of novel antiinflammatory targets for aprotinin. A better understanding of its mechanisms of action has led to the conclusion that aprotinin is a remarkable drug with the capacity to correct many of the imbalances that develop in the coagulation system and the inflammatory system after CPB. Nonetheless, it has been clinically underused for fear of causing thrombotic complications, a fear that in light of recent evidence may be unfounded.

Animals↗
PubMed2001

Preventing of chylothorax after oesophagectomy by routine pre-operative administration of oral cream.

The anatomy of the thoracic duct varies considerably. This can make it difficult to locate during oesophageal surgery, especially in the fasted patient. We describe the technique of administering cream orally before primary oesophageal surgery, to aid in the identification of the thoracic duct. The duct along with other lymphatic channels can then be ligated as appropriate, helping to reduce the incidence of post-operative chylothorax.

Administration, Oral↗
PubMed2001

Aprotinin: is it prothrombotic?

Controversy continues as to whether aprotinin (Trasylol) is prothrombotic. The recent discovery of the thrombin receptor family, known as the protease-activated receptor family (PAR) has been essential in aiding our understanding of the mechanism of action of aprotinin. Our results show that aprotinin has no effect on platelet aggregation induced by adrenaline, adenosine diphosphate, phorbol-12-myristate-13-acetate, collagen or PAR 1 agonist peptide. However, aprotinin inhibits thrombin-induced platelet activation as assessed by macroaggregation, microaggregation and platelet membrane calcium flux. Aprotinin inhibits proteolytic activation of platelets, but platelets can still be activated by non-proteolytic mechanisms.

Adenosine Diphosphate↗
PubMed2001

Effect of aprotinin (trasylol) on the inflammatory and thrombotic complications of conventional cardiopulmonary bypass surgery.

Before the discovery of its hemostatic properties, aprotinin was thought of as a potential anti-inflammatory agent. Its clinical introduction in 1987 to prevent blood loss during cardiac surgery [Royston 1987, van Oeveren 1987] led to its anti-inflammatory benefits being largely overlooked in favor of a vigorous debate centering on whether aprotinin may be pro-thrombotic when given to patients. In this article, we summarize evidence for the anti-inflammatory activity of aprotinin and discuss our recent contributions in this area. We also summarize the state of the thrombosis debate and discuss our recent evidence from purified platelets which shows that aprotinin is simultaneously hemostatic yet anti-thrombotic.

Animals↗
PubMed2000

The antithrombotic effect of aprotinin: actions mediated via the proteaseactivated receptor 1.

BACKGROUND: Despite aprotinin being in widespread clinical use to prevent bleeding during cardiac surgery, there remains concern that such a powerful hemostatic agent may also be prothrombotic, particularly in relation to coronary vein graft occlusion. The major thrombin receptor on platelets, protease-activated receptor 1 (PAR1) requires proteolytic cleavage to transmit activating signals. Here we have investigated the effect of aprotinin on thrombin-induced PAR1 activation of platelets. METHODS AND RESULTS: Proteolysis-dependent and -independent responses of washed platelets were studied in vitro. Platelet aggregation induced by trypsin was dependent on PAR1 (inhibited by the PAR1-specific antagonist peptide, FLLRN) and was completely blocked by aprotinin at doses more than 100 KIU/mL. Aggregation in response to thrombin, 1 nmol/L, was predominantly mediated through PAR1 and was inhibited 42.6% to 86.6% (P <.05-.001) by pharmacologic doses of aprotinin (50-160 KIU/mL). Aprotinin did not inhibit the nonproteolytic agonists collagen, epinephrine, adenosine diphosphate, or phorbol 12-myristate 13-acetate. Furthermore, blockade of the thrombin response by aprotinin did not prevent subsequent platelet aggregation through collagen or epinephrine. Experiments with intraplatelet Ca(2+) fluxes, which provided an earlier measure of platelet activation, placed the effect of aprotinin proximal to the PAR1 activation event. Since aprotinin did not inhibit platelet responses to the nonproteolytic PAR1 agonist peptide, SFLLRN, this implied that aprotinin acted by preventing PAR1 receptor cleavage by thrombin. CONCLUSIONS: Aprotinin inhibits thrombin-induced platelet activation by preventing proteolysis of the PAR1 receptor. These findings argue against aprotinin being prothrombotic and suggest instead that aprotinin may have significant antithrombotic effects.

Analysis of Variance↗