It is unknown whether and to what extent changes in various endothelial functions and adrenergic responsiveness are related to the development of microvascular complications in type 1 diabetes. Therefore, endothelium-dependent and endothelium-independent vasodilatation, endothelium-dependent hemostatic factors, and one and two adrenergic vasoconstrictor responses were determined in type 1 patients with and without microvascular complications. A total of 34 patients with type 1 diabetes were studied under euglycemic conditions on two occasions (11 without microangiopathy, 10 with proliferative and preproliferative retinopathy previously treated by laser coagulation, 13 with microalbuminuria, and 12 healthy volunteers also were studied). Forearm vascular responses to brachial artery infusions of N(G)-monomethyl-L-arginine (L-NMMA), sodium nitroprusside, acetylcholine (ACh), clonidine, and phenylephrine were determined. The ACh infusions were repeated during coinfusion of L-arginine. Furthermore, plasminogen activator inhibitor type 1 (PAI-1) activity, tissue plasminogen activator antigen levels, von Willebrand factor antigen levels, tissue factor pathway inhibitor (TFPI) activity, and endothelin-1 levels were measured. No differences in endothelium-dependent or endothelium-independent vasodilatation or adrenergic constriction were observed between the diabetic patients and the healthy volunteers. In comparison to the first ACh infusion, the maximal response to repeated ACh during L-arginine administration was reduced in the diabetic patients, except in the patients with proliferative and preproliferative retinopathy previously treated by laser coagulation. In these patients, the combined infusion of L-arginine and ACh resulted in an enhanced response. TFPI activity was elevated, and PAI-1 activity was reduced in the type 1 diabetic patients. Furthermore, PAI-1 activity was positively correlated with urinary albumin excretion (r = 0.48, P < 0.01) and inversely correlated with the vasodilatory response to the highest ACh dose (r = -0.37, P < 0.05). The response to the highest ACh and L-NMMA dose were positively correlated with mean arterial blood pressure (r = 0.32, P < 0.01; r = 0.41, P < 0.01, respectively). Forearm endothelium-dependent and endothelium-independent vasodilatation and adrenergic responsiveness were unaltered in type 1 diabetic patients with and without microvascular complications. Relative to healthy control subjects, endothelium-dependent vasodilatation was depressed during a repeated ACh challenge (with L-arginine coinfusion) in the diabetic patients without complications or with microalbuminuria. In contrast, this vasodilatation was enhanced in the patients with retinopathy. Elevation of TFPI was the most consistent marker of endothelial damage of all the endothelial markers measured.

This prospective non blind study in nine male experienced androgenic-anabolic steroid (AAS) users shows that AAS use is significantly associated with enhanced fibrinolytic activity compared with confirmed non using male bodybuilders as controls. Venous occlusion does not seem to have additional value in documenting this enhanced activity. It remains to be established whether this enhanced fibrinolytic activity is secondary to enhanced thrombin generation.

The aim of this study was to investigate the effects of eight weeks self-administration of high doses androgenic-anabolic steroids (AAS) in a stacking way on fibrinolytic activity in non elite male bodybuilders. A prospective, non blinded study design was chosen. The AAS group (AAS-G, n=7) consisted of experienced AAS users who were drug free for more than 3 months at start of the study. Non using bodybuilders served as controls (CO-G, n=7). Both groups were comparable with respect to age (32.3±6.8 vs.32.1±2.9, AAS-G resp. CO-G), height (179±4 vs. 174±6 cm), weight (82.8±8.7 vs. 85.2±8.4 kg), strength training experience (8.5±2.4 and 8.4±3.8 years) and weekly training hours(9.1±3.2 resp. 8.9±3.0). At start and after eight weeks training with (AAS-G) or without (CO-G) AAS use in all subjects blood samples before and after 10 minutes venuous occlusion (VO) were taken using a Biopool Stabilyte blood collection device. In each sample euglobulin clot lysis time(ECLT) was determined. Data are presented as mean ± s.d. ANOVA for repeated measures and paired t-tests for intra-group changes were used for statistical analysis. Level of significance was set at P<0.05. At start ECLT of both groups was comparable (101.3±15.4 and 106.8±17.4 minutes, AAS-G resp. CO-G). After eight weeks AAS use, ECLT before VO in the AAS-G was significantly decreased (101.3±15.4 to 80.2±25.0 min., P<0.02), whereas ECLT after VO remained unchanged. In CO-G no significant changes were observed after eight weeks. In conclusion, eight weeks self administration of high doses AAS in a stacking way enhances fibrinolytic activity as measured by euglobulin clot lysis time in non elite bodybuilders.

Chronic venous insufficiency is a common disease with skin changes, varicosity and leg ulceration. Several theories have been proposed to explain all the changes that occur. We recently saw several patients with Klinefelter's syndrome complicated by leg ulceration and all the typical skin changes of venous insufficiency. The underlying disease was however lacking. They all showed disturbances in their fibrinolytic parameters. In this article we discuss (local) fibrinolytic disturbances as a possible factor in the pathogenesis of the skin changes in chronic venous insufficiency.

Klinefelter's syndrome is the most frequent major abnormality of sexual differentiation in men with two or more X-chromosomes, and affects one in 500 males. The syndrome is characterized by eunuchoid body proportions, scanty facial and body hair, gynaecomastia, and small firm testes. Leg ulcers, especially in combination with hyperpigmentation, have been reported in association with Klinefelter's syndrome. Thromboembolic processes are also frequently observed. The leg ulcers in patients with Klinefelter's syndrome are usually attributed to venous insufficiency. We describe two patients with Klinefelter's syndrome associated with recurrent ulcers and hyperpigmentation on both legs, in whom no venous or other underlying cause could be found. The patients were not taking any drugs, in particular no supplemental androgen therapy. Both had normal plasma testosterone values. We detected increased activity of plasminogen activator inhibitor 1 (PAI-1), with only a partial decrease upon venous occlusion. A possible role for this inhibitor of fibrinolysis in the pathogenesis of ulceration is discussed.