13-HODE increases intracellular calcium in vascular smooth muscle cells.

13-Hydroxyoctadecadienoic acid (HODE) (2 microM) consistently increased porcine aortic and pulmonary artery smooth muscle cell calcium concentrations ([Ca2+]i), whereas 9-HODE and linoleic acid had no significant effect in the aortic cells and a much lesser effect in the pulmonary artery cells. A transient increase in [Ca2+]i occurred with as little as 50 nM 13-HODE. Structural specificity for elevation of [Ca2+]i also was seen with the monohydroxyeicosatetraenoic acids (HETEs), with 12-HETE but not 5- or 15-HETE increasing [Ca2+]i. 13-HODE, but not 9-HODE, increased smooth muscle cell guanosine 3',5'-cyclic monophosphate (cGMP) levels. The [Ca2+]i increase produced by 13-HODE was dependent on extracellular calcium and was inhibited by the calcium channel blockers verapamil and nifedipine and by KT-5823, a cGMP-dependent kinase inhibitor. A similar increase in [Ca2+]i was produced by 8-bromo-cGMP. These results suggest that 13-HODE, a 15-lipoxygenase product formed from linoleic acid, can act as a lipid mediator in vascular smooth muscle. It raises smooth muscle cGMP, causing a secondary increase in [Ca2+]i due to Ca2+ influx through a cGMP kinase-dependent L-type channel.

Anaesthesia for resection of lesions of the trachea and main bronchi using the neodymium yttrium aluminium garnet (Nd YAG) laser. A report of 75 treatments in 52 patients.

The management of anaesthesia and outcome of 75 treatments in 52 patients are discussed. Total intravenous anaesthetic techniques were used with venturi ventilation via a rigid bronchoscope. A number of complications occurred, but there was no death or major surgical complication. All complications except one were apparent intraoperatively or in the recovery room. As the considerable risk of intraoperative hypoxia was considered to outweigh the minimal risk of intratracheal fire or explosion, no attempt was made to limit inspired oxygen concentration (FIO2) during the application of the laser. The results of ventilation/perfusion studies and a recent diagnostic bronchoscopy were very helpful in patient selection.

The relationship between venous pressure and vein wall fibrinolytic activity.

Vein wall fibrinolytic activity has been shown to be greater in the arms than the legs and it has been suggested that this difference is related to the greater hydrostatic venous pressure in the leg. Vein wall fibrinolytic activity and foot vein pressure has been measured in 40 legs from 30 patients, 25 with uncomplicated varicose veins and 15 with lipodermatosclerosis. No statistically significant correlation could be demonstrated between vein wall fibrinolytic activity and measured foot vein pressure.

Venous lipodermatosclerosis: treatment by fibrinolytic enhancement and elastic compression.

The value of fibrinolytic enhancement with an anabolic steroid (stanozolol) combined with elastic stockings in treating venous lipodermatosclerosis was assessed in a six-month double-blind cross-over trial. Thirty-four legs of 23 patients in whom other treatments had failed were studied. The patients were randomly divided into two groups who were treated with either stanozolol plus elastic stockings or placebo plus elastic stockings for three months, and then vice versa. Treatment with or without stanozolol caused the area of lipodermatosclerosis to decrease, but the rate of healing when patients took stanozolol was double that when they took the placebo, and this was assumed to be biologically important. Stanozolol also reduced the incidence of extravascular fibrin detected in skin biopsy specimens. The elastic stocking with placebo produced significant decreases in leg volume, ankle circumference, and skin thickness. Stanozolol is valuable in treating intractable lipodermatosclerosis, giving relief of pain and reducing induration, inflammation, tenderness, and pigmentation.

The fibrinolytic activity of varicose veins.

The plasma fibrinogen concentration, plasma fibrinolytic activity and the vein wall fibrinolytic activity of hand, groin, knee, ankle and perforating veins have been studied in 10 patients with skin changes in the lower leg secondary to venous disease (lipodermatosclerosis), in 10 patients with uncomplicated varicose veins and in 17 normal volunteers undergoing surgery. There was significantly more vein wall fibrinolytic activity in normal volunteers than in the patients with lipodermatosclerosis, not only in the ankle (P less than 0.001) but also in the hand (P less than 0.05). It is suggested that the reduced tissue fibrinolytic activity is a causative factor in the skin changes and ulceration of the post-phlebitic leg, and that since the reduced activity is not confined to the leg, it may be a primary systemic defect rather than a state secondary to venous congestion.

Treatment of Raynaud's phenomenon by fibrinolytic enhancement.

Twenty patients with advanced Raynaud's phenomenon, in 14 of whom it was secondary to scleroderma, were treated with stanozolol, an anabolic steroid that enhances natural fibrinolysis. All showed an increase in hand blood flow and a reduction in symptoms during treatment. This response may have been caused by the lysis of fibrin deposited in the digital arteries and the reduction of plasma viscosity. Stanozolol is a useful addition to the treatment of patients with advanced Raynaud's phenomenon who have trophic changes.

Treatment of liposclerosis of the leg by fibrinolytic enhancement: a preliminary report.

Fourteen patients with longstanding lipodermatosclerosis of their lower legs, secondary to venous disease in 11, were treated for three months with stanozolol, a drug that enhances fibrinolytic activity. No other treatment was given and no change made in existing treatment. All the patients improved. Two were cured in three months, three were able to stop treatment in the next three to 11 months, and the other nine continued to improve. Fibrinolytic enhancement, with stanozolol, seems to be a worthwhile addition to the treatment of venous liposclerosis and deserves further study.

Idiopathic recurrent superficial thrombophlebitis: treatment with fibrinolytic enhancement.

Sixteen patients with idiopathic recurrent superficial thrombophlebitis were shown to have a defect of blood and tissue fibrinolytic activity. After six months' treatment with stanozolol their mean dilute blood clot lysis time and plasma fibrinogen fell significantly and the mean fibrin plate lysis area increased. Attacks of thrombophlebitis stopped completely in 13 patients, though five patients later suffered recurrences and phenformin had to be added to their treatment. Fibrinolytic enhancement with stanozolol seems to be effective in this previously intractable condition, and regular blood studies will indicate which patients also need phenformin.

Blood and vein-wall fibrinolytic activity in health and vascular disease.

The resting blood fibrinolytic activity of 120 normal subjects and 294 patients with various forms of vascular disease was assessed by measuring the dilute blood clot lysis time and fibrin plate lysis area before and after 10 minutes of venous congestion. The tissue fibrinolytic activity of several of these subjects was assessed in vein biopsy specimens. The results suggested that there was a correlation between blood and tissue fibrinolytic activity and that certain venous diseases, particularly recurrent superficial thrombophlebitis and venous liposclerosis, were associated with a deficiency of blood and tissue fibrinolytic activity.

Changes in the blood fibrinolytic activity after surgery (the effect of deep vein thrombosis and malignant disease.

The changes in blood fibrinolytic activity before and after operation have been investigated in 56 patients. The results have been analysed to assess the effect of the presence of malignant disease and the development of deep vein thombosis. The results show that patients with malignant disease and those with thrombosis have a fibrinolytic shut-down. This shut-down appears to be secondary to these two conditions and not the cause of the thrombosis. Patients without carcinoma and without thrombosis do not have a significant shut-down. The fibrinolytic shut-down results from a reduced release of activator from the peripheral store, not a reduction in the size of the store itself.