Whole body, adipose tissue, and forearm norepinephrine kinetics in lean and obese women.

We evaluated whole body and regional (subcutaneous abdominal adipose tissue and forearm) norepinephrine (NE) kinetics in seven lean (body mass index 21.3 +/- 0.5 kg/m2) and six upper body obese (body mass index 36.4 +/- 0.4 kg/m2) women who were matched on fat-free mass. NE kinetics were determined by infusing [3H]NE and obtaining blood samples from a radial artery, a deep forearm vein draining mostly skeletal muscle, and an abdominal vein draining subcutaneous abdominal fat. Mean systemic NE spillover tended to be higher in obese (2.82 +/- 0.49 nmol/min) than in lean (2.53 +/- 0.40 nmol/min) subjects, but the differences were not statistically significant. Adipose tissue and forearm NE spillover rates into plasma were greater in lean (0.91 +/- 0.08 pmol. 100 g tissue-1. min-1 and 1.01 +/- 0.09 pmol. 100 ml tissue-1. min-1, respectively) than in obese (0.26 +/- 0.05 pmol. 100 g tissue-1. min-1 and 0.58 +/- 0.11 pmol. 100 ml tissue-1. min-1, respectively) subjects (P < 0.01). These results demonstrate that adipose tissue is an active site for NE metabolism in humans. Adipose tissue NE spillover is considerably lower in obese than in lean women, which may contribute to the lower rate of lipolysis per kilogram of fat mass observed in obesity.

Recurrent gastrointestinal bleeding: use of thrombolysis with anticoagulation in diagnosis.

PURPOSE: To determine the safety and diagnostic accuracy of a provocative protocol with heparin and urokinase to induce bleeding and determine the source in patients with chronic gastrointestinal hemorrhage. MATERIALS AND METHODS: Nine patients had gastrointestinal bleeding from an indeterminate source and had negative results from esophagogastroduodenoscopy, colonoscopy, small-bowel examination, and angiography. Ten provocative bleeding studies were performed prospectively. Patients had no clinical evidence of bleeding within 2 days before the study. Intravenous administration of heparin and urokinase was performed systemically during a 4-hour period while scintigraphy was performed continuously. Mesenteric angiography was performed immediately in patients in whom substantial gastrointestinal bleeding was detected at scintigraphy. RESULTS: The provocative protocol was successful in inducing scintigraphically detectable hemorrhage in four (40%) studies within 4 hours. In two of these four studies, the source of hemorrhage was determined and treated with embolization or surgery. Three (30%) studies demonstrated scintigraphic evidence of hemorrhage only at delayed imaging (8-24 hours after initiation of the study). The remaining three (30%) studies did not show active bleeding. No complications occurred, including hemodynamic instability or uncontrollable decreases in hematocrit. CONCLUSION: Since this protocol with heparin and urokinase enabled determination of the bleeding source in only two of 10 studies, protocol modifications are necessary before this intervention is used widely.

Effects of antiplatelet drugs on dialysis-associated platelet deposition in polytetrafluoroethylene grafts.

Hemodialysis is associated with platelet deposition in polytetrafluoroethylene (PTFE) graft fistulas. We determined whether aspirin or ticlopidine would modify this response. Patients on chronic hemodialysis with forearm loop PTFE fistulas were studied. Platelets labeled with 111indium were injected and a baseline scan of the fistula arm was made with a large field of view gamma camera. After a routine dialysis treatment, a second scan was performed within 1 hour. Four weeks later, a repeat labeled platelet study was conducted after taking either aspirin 325 mg/d or ticlopidine 250 mg/d orally for 7 days. Images were computer analyzed by drawing seven standardized regions along each graft. The counts per second per pixel in postdialysis images were compared with predialysis images for each region and a percent uptake compared with the predialysis image was calculated. Regions with dialysis-induced uptake of more than 1.5-fold compared with the predialysis image before antiplatelet drug therapy were compared with these same regions after therapy. Six patients were studied before and after aspirin therapy. Uptakes larger than 1.5-fold over predialysis images were found in 12 of 40 regions and were 292% +/- 50% (+/-SEM) before and 193% +/- 25% of predialysis values after aspirin (P = 0.02, paired t-test). Uptakes in the remaining regions were 107% +/- 4% before and 115% +/- 6% after aspirin (P = NS). A second group was studied before and after ticlopidine (n = 5). Uptakes increased by more than 1.5-fold compared with predialysis images in 19 of 30 regions and had a median of 286% increased uptake (mean, 785% +/- 374%) before and 160% (153% +/- 10%) after drug therapy (P < 0.001, Wilcoxon). Uptakes in the remaining regions were 116% +/- 5% before and 134% +/- 13% after drug therapy (P = NS). Platelet aggregation studies suggested compliance with both drugs. These studies show that these antiplatelet drugs reduce, but do not completely prevent, dialysis-associated radiolabeled platelet deposition in PTFE grafts.