C L McGuinness

The Role of the Monocyte in the Generation and Dissolution of Arterial and Venous Thrombi

Monocyte infiltration into forming thrombus has been demonstrated in experimental models of venous thrombosis developed in our laboratories. These cells produce and release plasminogen activators as the thrombus organises and resolves. Monocytes are also capable of assembling and releasing procoagulant factors and the evidence for their importance in thrombogenesis is reviewed. The ability of monocytes to maintain this fibrinolytic balance suggests that they may have a role in both thrombosis and thrombus resolution. Control of the mechanisms which regulate these activities may therefore be important in preventing thrombus formation or stimulating its resolution.

Randomized clinical trial of three-layer paste and four-layer bandages for venous leg ulcers†‡

Both four‐layer and three‐layer paste bandages are widely used in the treatment of venous leg ulcers. The aim of this study was to compare the efficacy of these two bandaging regimens.

HIGH AND CONSTANT PLASMA LEVELS OF TISSUE PLASMINOGEN ACTIVATOR AND PEG-HIRUDIN CAN BE ACHIEVED BY SUBCUTANEOUS DELIVERY

Intramural thrombosis is a consistent finding in the arteries of patients who die following coronary angioplasty. This thrombosis is thought to have a role in restenosis, which is a common complication of coronary angioplasty. It has been hypothesised that antithrombotics such as hirudin or tissue-type plasminogen activator (tPA), may be therapeutically useful following angioplasty. This report describes the bioavailability of both agents following subcutaneous (sc) injection in cholesterol-fed rabbits. Intravenously delivered tPA has a half-life of 3-5 minutes. The half-life of intravenously administered hirudin is less than one hour in many species. In order to prolong the duration of action recombinant hirudin was conjugated to polyethylene glycol (PEG). Polyethylene glycol conjugated recombinant hirudin (PEG-rH) (0.7 mg/kg) antigen and activity were measurable after just 1 hr, reaching a maximum (663 and 884 ng/ml respectively) at 12 hours. Significant levels were present in rabbit plasma 24 hours after injection. Subcutaneously delivered recombinant (r-tPA) (1 mg/kg) was present in significant amounts 1 hr after injection, reaching a maximum (92 IU/ml) at 2 hours. Levels of tPA at 9 hours were approximately 80x normal circulating levels. High and constant levels of functional activity of both PEG-rH and r-tPA in rabbit plasma are achieved by subcutaneous delivery.

Evaluation of duplex ultrasonography versus other investigations in the diagnosis of ‘venous aetiology’ in patients with leg ulcers

The aim was to compare duplex imaging, venography, foot volumetry and air plethysmography in patients with healed leg ulcers considered to be caused by venous disease to discover whether duplex scanning alone could confirm a venous aetiology. The importance of isolated reflux in a segment of the deep system below a competent valve was assessed.