Fibrinolytic markers and vasodilatory capacity following acute exercise among men of differing training status.

We evaluated the effect of differing physical activity patterns on fibrinolysis and vasodilatory capacity using a cross-sectional design with 16 endurance-trained (ET) (mean+/-SE) (28+/-6 years), 14 resistance-trained (RT) (28+/-7 years), and 10 untrained (UT) (26+/-7 years) men. t-PA and PAI-1 activity and t-PA antigen were measured before and after a maximal treadmill test (VO2peak). Vasodilatory capacity was assessed using strain-gauge plethysmography on the forearm following reactive hyperemia (RH) before and after the treadmill test. The ET group had a smaller body mass index (BMI) (22.8+/-0.5 ET, 26.4+/-0.4 RT, 25.1+/-0.8 UT kg m(-2)) (P<0.05) and a greater VO2peak (57+/-1 ET, 42+/-2 RT, 45+/-2 UT mL min(-1) kg(-1)) (P<0.05). Peak vasodilatory capacity (29.7+/-2 ET, 32.0+/-2 RT, 27.4+/-2 UT mL min(-1) 100 mL of tissue) was similar between groups before and after exercise. Area under the curve for forearm blood flow was greater following acute exercise (212 vs. 122, P<0.05), again with no differences between groups. t-PA activity and antigen increased following maximal exercise in all groups (P<0.0001), with no group differences. PAI-1 activity decreased the least in RT after exercise (70% decrease vs. 86% ET and 82% UT; P<0.05). The change in t-PA activity with exercise was not related to exercise-induced change in overall vasodilatory capacity. These findings demonstrate that in healthy young men different physical activity patterns do not appear to impact the exercise-induced changes in fibrinolysis or vasodilatory capacity.

Changes in blood coagulation markers associated with uterine artery embolization for leiomyomata.

PURPOSE: To determine whether a transient hypercoagulable state is induced by the uterine artery embolization (UAE) procedure. MATERIALS AND METHODS: Serial periprocedure blood samples were obtained from 27 patients undergoing the UAE procedure. Five blood samples were obtained from each patient at set time intervals: before the procedure (for baseline determination), immediately before and after embolization of the uterine arteries, 90 minutes after conclusion of the procedure, and between 18 and 24 hours later. Each blood sample was analyzed for the peripheral levels of the following parameters: thrombin-antithrombin complex (TAT), prothrombin fragment 1.2 (F1.2), platelet factor 4 (PF4), D-dimer, and plasmin-alpha(2)-antiplasmin complex (PAP). For each parameter, the baseline values were statistically compared with the pre- and postembolization values for each individual to detect change over time. Overall and global occasion effects for continuous variables were assessed with the Friedman statistic and individual comparisons between occasions with the Wilcoxon signed-rank test. RESULTS: No evidence was found for a difference in coagulability among the five occasions for D-dimer (P =.7645) or PF4 (P =.09). All three of the remaining measures were found to have statistically significant differences (P <.0001 for F1.2, P =.0026 for PAP, and P =.0006 for TAT). No evidence was found for a difference between preprocedure and preembolization levels for these three latter parameters (P =.595 for F1.2, P =.128 for PAP, P =.9705 for TAT). Hypercoagulability potential as measured by prothrombinase and F1.2 generation increased between preembolization samples and each of the successive postprocedure samples (P <.0001, P <.0001, P =.0082), whereas PAP increased at 90 minutes (P =.0023) and TAT increased immediately after embolization (P <.0001). No clinically apparent thrombotic complications occurred among any of the patients studied. CONCLUSIONS: Surrogate markers of hypercoagulability increase as a result of UAE, suggesting that a prothrombotic state may result after the procedure.

Initial clinical trial of oral TAC-101, a novel retinoic acid receptor-alpha selective retinoid, in patients with advanced cancer.

PURPOSE: The goals of this study were to determine the safety, toxicity, and pharmacokinetics of TAC-101, a novel synthetic retinoic acid receptor-alpha (RAR-alpha) selective retinoid, in patients with advanced cancer. PATIENTS AND METHODS: Twenty-nine patients at two centers received oral TAC-101 at doses ranging from 12 to 34 mg/m(2)/d. Pharmacokinetic sampling was performed on days 1 and 28. RESULTS: The most frequent toxicities were myalgia/arthralgia, fatigue, and triglyceridemia. No dose-limiting toxicities were observed within the first 28 days up to 28 mg/m(2). However, seven of 21 patients experienced venous thromboembolic events (VTEs) during TAC-101 treatment. Eight additional patients who received 34 mg/m(2) were treated after a hypercoagulable work-up to exclude potential risk factors for VTE, and two of eight patients subsequently experienced VTEs. The maximum tolerated dose was exceeded at 34 mg/m(2)/d within the first 28 days, with one grade 3 hypertriglyceridemia, two grade 3 myalgia/arthralgia, and one grade 3 fatigue. One patient with advanced non-small-cell lung cancer had a complete response. No other responses were observed. No autoinduction of metabolism was observed with dosing over 28 days. CONCLUSION: This is the first human clinical study with TAC-101, a RAR-alpha selective retinoid. Musculoskeletal toxicity and hypertriglyceridemia were observed characteristics of previously studied retinoids. The recommended phase II dose is 24 mg/m(2) with this treatment schedule. Alternative treatment schedules and prospective evaluation of thrombotic risk will be investigated in subsequent studies.