This preliminary analysis of a phase II study suggests that high-dose rTNF alpha can be administered with acceptable toxicity by ILP with dopamine and hyperhydration. Tumor responses can be evidenced in melanoma and sarcoma. Furthermore, combination of rTNF alpha, rIFN-gamma, and melphalan seems to achieve high efficacy with minimal toxicity, even after failure of prior therapy with melphalan alone.

Brimioulle, Serge, Pierre Wauthy, Patricia Ewalenko, Benoît Rondelet, Franç oise Vermeulen, Franç ois Kerbaul, and Robert Naeije. Single-beat estimation of right ventricular end-systolic pressure-volume relationship. Am J Physiol Heart Circ Physiol 284: H1625-H1630, 2003. First published January 16, 2003 10.1152/ajpheart.01023.2002.-Assessement of right ventricular (RV) contractility from endsystolic pressure-volume relationships (ESPVR) is difficult due to problems in measuring RV instantaneous volume and to effects of changes in RV preload or afterload. We therefore investigated in anesthetized dogs whether RV ESPVR and contractility can be determined without measuring RV volume and without changing RV preload or afterload. The maximal RV pressure of isovolumic beats (P max) was predicted from isovolumic portions of RV pressure during ejecting beats and compared with Pmax measured during the first beat after pulmonary artery clamping. In RV pressure-volume loops obtained from RV pressure and integrated pulmonary arterial flow, end-systolic elastance (Ees) was assessed as the slope of Pmax-derived ESPVR, pulmonary artery effective elastance (Ea) as the slope of end-diastolic to end-systolic relation, and coupling efficiency as the Ees-to-Ea ratio (Ees/ Ea). Predicted Pmax correlated with observed Pmax (r ϭ 0.98 Ϯ 0.02). Dobutamine increased Ees from 1.07 to 2.00 mmHg/ml and Ees/Ea from 1.64 to 2.49, and propranolol decreased Ees/Ea from 1.64 to 0.91 (all P Ͻ 0.05). After adrenergic blockade, preload reduction did not affect Ees, whereas hypoxia and arterial constriction markedly increased Ea and somewhat increased Ees due to the Anrep effect. Low preload did not affect Ees/Ea and high afterload decreased Ees/Ea. In conclusion, in the right ventricle 1) Pmax can be calculated from normal beats, 2) Pmax can be used to determine ESPVR without change in load, and 3) Pmax-derived ESPVR can be used to assess ventricular contractility and ventricular-arterial coupling efficiency. contractility; preload; afterload; pulmonary hypertension; hypoxia LEFT VENTRICULAR CONTRACTILITY is commonly defined by the end-systolic pressure-volume relationship (ESPVR) (15,16,24). In the right ventricle (RV), the concept of ESPVR is also valid (8, 20) but it is difficult to apply in practice. The major problem is the difficulty in measuring instantaneous RV volume in vivo. In 1988, Kass (13) summarized the limitations of available methods and mentioned the potential of conductance volumetry. Although not completely validated for measurement of instantaneous volume, conductance has been used repeatedly to generate pressure-volume loops in animals and humans (34). The method remains difficult and time consuming and is therefore predominantly used as a research tool (31). A second problem may be the identification of end systole on triangle-shaped RV pressure-volume curves. Several investigators (9, 20) determined ESPVR from end-ejection pressures and volumes, but end ejection and end systole are known to occur at different times in the ...

A transient increase in PA pressure persistently worsens PA hemodynamics, RV contractility, RV-PA coupling, and cardiac output. Dobutamine restores RV-PA coupling and cardiac output better than norepinephrine because of its more pronounced inotropic effect.

Postoperative nausea and vomiting (PONV) are unpleasant, often underestimated side effects of anaesthesia and surgery, not devoid of medical complications. Prevention with antiemetics is only partially effective. Propofol has been shown recently to possess antiemetic properties in several situations. In this prospective, randomized, controlled trial, we have compared the antiemetic efficacy of subhypnotic doses of propofol, with Intralipid as placebo, after thyroidectomy. We studied 64 patients of both sexes, aged 22-71 yr, ASA I or II, undergoing thyroidectomy. After premedication with a benzodiazepine, balanced anaesthesia was produced with isoflurane and nitrous oxide in oxygen, and supplementary analgesia with fentanyl i.v. as required. Postoperative analgesia was provided with non-opioids, and piritramide 0.25 mg kg-1 i.m. on demand. Patients were allocated randomly and blindly to receive a 20-h infusion of either propofol or 10% Intralipid 0.1 ml kg-1 h-1. Intralipid, the excipient of propofol, was chosen as placebo as it is devoid of antiemetic effects. Sedation scores, respiratory and cardiovascular variables, and incidence of PONV were assessed every 4 h for 24 h. Pulse oximetry and ECG were monitored continuously. Both groups were comparable in characteristics, surgical and anaesthesia procedures, amount of opioids given during and after operation, and total amount of the study drug infused after operation. Occurrence of PONV was similar before the start (propofol 41%, Intralipid 50%) and after completion (propofol 0.64%, Intralipid 1.6%) of infusion and decreased with time in both groups during the infusion. However, symptoms were reduced to nil with propofol but persisted and were more severe with Intralipid during infusion (P < or = 0.01). The overall incidence of PONV during infusion was 10% (three of 32 patients) in the propofol group and 65% (21 of 32 patients) in the Intralipid group. Cardiovascular and respiratory variables, and SpO2 were unaltered, and sedation decreased similarly with time in both groups. We conclude that propofol, given at subhypnotic doses, effectively reduced the incidence of PONV without untoward sedative or cardiovascular effects.