Background-Apelin, the endogenous ligand for the novel G protein-coupled receptor APJ, has major cardiovascular effects in preclinical models. The study objectives were to establish the effects of acute apelin administration on peripheral, cardiac, and systemic hemodynamic variables in healthy volunteers and patients with heart failure. Methods and Results-Eighteen patients with New York Heart Association class II to III chronic heart failure, 6 patients undergoing diagnostic coronary angiography, and 26 healthy volunteers participated in a series of randomized, double-blind, placebo-controlled studies. Measurements of forearm blood flow, coronary blood flow, left ventricular pressure, and cardiac output were made by venous occlusion plethysmography, Doppler flow wire and quantitative coronary angiography, pressure wire, and thoracic bioimpedance, respectively. Intrabrachial infusions of (Pyr 1 )apelin-13, acetylcholine, and sodium nitroprusside caused forearm vasodilatation in patients and control subjects (all PϽ0.0001). Vasodilatation to acetylcholine (Pϭ0.01) but not apelin (Pϭ0.3) or sodium nitroprusside (Pϭ0.9) was attenuated in patients with heart failure. Intracoronary bolus of apelin-36 increased coronary blood flow and the maximum rate of rise in left ventricular pressure and reduced peak and end-diastolic left ventricular pressures (all PϽ0.05). Systemic infusions of (Pyr 1 )apelin-13 (30 to 300 nmol/min) increased cardiac index and lowered mean arterial pressure and peripheral vascular resistance in patients and healthy control subjects (all PϽ0.01) but increased heart rate only in control subjects (PϽ0.01). Conclusions-Acute apelin administration in humans causes peripheral and coronary vasodilatation and increases cardiac output. APJ agonism represents a novel potential therapeutic target for patients with heart failure. (Circulation.
Four treatment regimens for patients with specified combinations of low back pain and sciatica were evaluated. The largest group studied had low back pain with limited straight-leg raising (SLR) and in them the beneficial effect of manipulation in hastening pain relief was highly significant. In similar patients without limitation of SLR, the effect was of borderline significance. In all the other groups, treated patients also recovered more quickly than their controls. Traction, for patients with low back pain and sciatica, and epidural injections when a root palsy was present also produced some significant pain relief. The effect of sclerosants for back pain was less clear.
From 1988 to 1991, 17 patients with malignant periacetabular tumors underwent limbsparing surgery and reconstruction using the saddle prosthesis. There were 8 patients with primary malignant lesions (Group l), and 9 patients with metastatic or systemic tumor involving the periacetabular pelvis (Group 2). All resections included excision of the acetabulum. Patients ranged in age from 24 to 76 years (average, 59.8 years). Local control was achieved in all patients. Wide margins were obtained in all patients with primary pelvic tumors. Functional outcomes were rated as follows excellent (lo), good (2), fair (l), and poor (4). Three patients, all of whom had pul-
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