In febrile neutropenic patients, systematic CT scan allows earlier diagnosis of IPA. Early antifungal treatment, combined with surgical resection if necessary, improves IPA prognosis dramatically in these patients.

No abstract

Patients with haematological malignancies requiring an antifungal therapy were randomly assigned to receive amphotericin B diluted in either 5% dextrose or in fat emulsion (Intralipid). Twenty-one patients were included in each group. Mean duration of amphotericin B therapy was 8.4 days in the dextrose group and 12.8 days in the Intralipid group. Amphotericin B infusion induced chills in 16 of 21 patients in the dextrose group and in 5 of 21 in the Intralipid group (P = 0.0008). Serum creatinine increased > 75% from baseline in ten patients in the dextrose group compared with only two in the Intralipid group (P = 0.007). A > or = 50% decrease of creatinine clearance was observed in 14 of 21 patients in the dextrose group compared with seven of 21 patients in the Intralipid group (P = 0.025). No difference was found between the two groups with regard to potassium and sodium requirement. Among patients who did not receive magnesium before antifungal therapy, magnesium supplementation was required more frequently in the dextrose group (8/12 vs 2/11; P = 0.02). Concomitant amikacin dosage reduction was more frequent in the dextrose group due to nephrotoxicity (7/19 vs 2/20; P = 0.045). A similar difference in vancomycin dosage reduction was observed between the two groups (12/20 vs 5/19; P = 0.03).

1 The possible existence of a b 3 -adrenoceptor (b 3 -AR) in human near-term myometrium was investigated by in vitro functional and biochemical studies and analysis of mRNA expression. 2 SR 59119A and SR 59104A and CGP 12177 (two selective agonists and a partial agonist, respectively, of the b 3 -AR), salbutamol and terbutaline (b 2 -AR agonists) each produced a concentration-dependent relaxation of the myometrial spontaneous contractions. There were no di erences in pD 2 values for the relaxing potencies of terbutaline, salbutamol, CGP 12177 and SR 59119A. The rank order for their relaxing e cacies was SR 59119A4SR 59104A4terbutali-ne&salbutamol&CGP 12177 (E max =52+7%, 42+12% and&30% respectively). 3 Propranolol, a b 1 -and b 2 -AR antagonist, and ICI 118551, a b 2 -AR antagonist (both at 0.1 mM), did not a ect the SR 59119A-induced relaxation whereas SR 59230A, a selective b 3 -AR antagonist (1 mM), signi®cantly reduced the maximal relaxing e ect of SR 59119A. 4 SR 59119A and salbutamol induced a signi®cant increase in cyclic AMP levels that was antagonized by SR 59230A but not by propranolol for SR 59119A, and by propranolol but not by SR 59230A for salbutamol. 5 The b 3 -AR mRNA was positively expressed in myometrium preparations in a reverse transcription polymerase chain assay. 6 The results presented provide the ®rst evidence for the existence of the b 3 -AR subtype in human near-term myometrium and suggest that the e ects of SR 59119A might be mediated through an increase in cyclic AMP level.

HMG-CoA reductase inhibitors improve endothelial function and exert antiproliferative effects on vascular smooth muscle cells of systemic vessels. This study was aimed to assess the protective effects of pravastatin (an HMG-CoA reductase inhibitor) against monocrotaline-induced pulmonary hypertension in rats. Pravastatin (PS, 10 mg/kg/day) or vehicle were given orally for 28 days to Wistar male rats injected or not with monocrotaline (MC, 60 mg/kg intraperitonealy) and treated or not by N(omega)-nitro-L-arginine methyl ester (L-NAME) 15 mg/kg/day. At 4 weeks, monocrotaline-injected rats developed severe pulmonary hypertension, with an increase in right ventricular pressure (RVP) and right ventricle/left ventricle+septum weight ratio (RV/LV+S), associated with a decrease in pulmonary artery dilation induced either by acetylcholine or sodium nitroprusside. Hypertensive pulmonary arteries exhibited an increase in medial thickness, medial wall area, endothelial cell apoptosis, and a decrease of endothelial nitric oxide synthase (eNOS) expression. Monocrotaline-rat lungs showed a significant decrease of eNOS expression (4080+/-27 vs 12189+/-761 arbitrary density units [ADU] for MC and control groups respectively, P<0.01) and a significant increase of cleaved caspase-3 expression by western blotting (Control=11628+/-2395 vs MC=2326+/-2243 ADU, P<0.05). A non-significant trend toward a reduced mortality was observed with pravastatin (relative risk of death = 0.33; 95% confidence interval [0.08-1.30], P= 0.12 for MC+PS vs MC groups). Pravastatine induced a protection against the development of the pulmonary hypertension (RVP in mmHg: 30+/-3 vs 45+/-4 and RV/LV+S: 0.46+/-0.04 vs 0.62+/-0.05 for MC+PS and MC groups respectively, P<0.05) and was associated with a significant reduction of MC-induced thickening (61+/-6 mum vs 81+/-3 mum for MC+PS and MC groups respectively, P= 0.01) of the medial wall of the small intrapulmonary arteries. Pravastatin partially restored acetylcholine-induced pulmonary artery vasodilation in MC rats (Emax=65+/-5% and 46+/-3% for MC+PS and MC group respectively, P<0.05) but had no effect on acetylcholine-induced pulmonary artery vasodilation in MC+L-NAME rats. It also prevented apoptosis and restored eNOS expression of pulmonary artery endothelial cells, as well as in the whole lung. Pravastatin reduces the development of monocrotaline-induced pulmonary hypertension and improves endothelium-dependent pulmonary artery relaxation, probably through a reduced apoptosis and a restored eNOS expression of endothelial cells.