Determinants of prostate cancer-specific survival after radiation therapy for patients with clinically localized prostate cancer.

PURPOSE: Identifying pretreatment and posttreatment predictors of time to prostate cancer-specific death (PCSD) after external-beam radiation therapy (RT) was the subject of this study. PATIENTS AND METHODS: A Cox regression analysis was used to evaluate the ability of the pretreatment risk group to predict time to PCSD for 381 patients who underwent RT for clinically localized prostate cancer. Posttreatment factors analyzed for the 94 patients who experienced prostate-specific antigen (PSA) failure included the time to PSA failure, the posttreatment PSA doubling time (DT), and the timing of salvage hormonal therapy. RESULTS: Despite the median age of 73 years at diagnosis, 45% of patients with high-risk disease were estimated to die from prostate cancer within 10 years after RT compared with 0% (P =.004) and 6% (P =.05) for patients with low- or intermediate-risk disease, respectively. Predictors of time to PCSD after PSA failure included PSA DT (P =.01) and delayed use of hormonal therapy (P 相似文献   

Monoclonal antibodies protect against respiratory syncytial virus infection in mice.

Twenty-five monoclonal antibodies (Mab) to respiratory syncytial virus (RSV) and two to hepatitis B virus were inoculated intravenously into mice. Twenty-four hours later the mice were challenged intranasally with RSV. Eleven of 14 Mab against fusion protein and four out of six Mab against a larger glycoprotein (GP84) significantly reduced the titre of RSV in the lungs when mice were killed 5 days later. Five Mab against three other RSV proteins and two Mab against hepatitis B virus had no significant effect on RSV infection. These results indicated that serum IgG against one epitope on the fusion protein and another on the larger glycoprotein (GP84) will completely protect mice against challenge. These epitopes are primary candidates for an RSV vaccine produced by techniques of gene cloning and peptide synthesis.     

Alpha1-adrenergic stimulation of ACTH secretion in vivo in the rat

The α-adrenergio agonist phenylephrine (100 μg, i.v.) causes a rapid 5- to 10-fold elevation of plasma ACTH levels 5 min after its administration in adult ovariectomized rats, the concentration of the hormone remaining elevated up to at least 2h. Epinephrine (10 μg) causes also a rapid but shorter-lived stimulation of ACTH secretion. While having no effect alone under basal conditions (conscious freely-moving animals), the highly specific α₁-adrenergic antagonist prazosin (0.25 μg) almost completely reverses the stimulatory effect of phenylephrine. Pretreatment with dexamethasone inhibits basal plasma ACTH levels by 70% and almost completely prevents the stimulatory effect of phenylephrine on this parameter. Plasma levels of α-MSH, on the other hand, are only stimulated 1-fold above control 5 min after the administration of phenylephrine and are insensitive to corticosteroid treatment. Based on the specificity of action of prazosin on postsynaptic α₁-adrenergic receptors and of dexamethasone on the anterior lobe of the pituitary gland, the present data indicate that phenylephrine is a potent stimulator of ACTH secretion by a direct action on an α₁-adrenergic receptor in corticotrophs of the adenohypophysis. They also support the suggestion that epinephrine and/or norepinephrine could be involved as physiological corticotropin-releasing factor(s).     

Pharmacokinetics of etoricoxib in patients with renal impairment

The effect of renal insufficiency on the pharmacokinetics of etoricoxib, a selective inhibitor of cyclooxygenase-2, was examined in 23 patients with varying degrees of renal impairment (12 moderate [creatinine clearance between 30 and 50 mL/min/1.73 m2], 5 severe [creatinine clearance below 30 mL/min/1.73 m2], and 6 with end-stage renal disease requiring hemodialysis) following administration of single 120-mg oral doses of etoricoxib. Even the most severe renal impairment was found to have little effect on etoricoxib pharmacokinetics. The low recovery of etoricoxib in dialysate (less than 6% of the dose) supports that hemodialysis also has little effect on etoricoxib pharmacokinetics, and binding of etoricoxib to plasma proteins was generally unaffected by renal disease. Single doses of etoricoxib were generally well tolerated by patients with renal impairment. Based on pharmacokinetic considerations, dosing adjustments are not necessary for patients with any degree of renal impairment. However, because patients with advanced renal disease (creatinine clearance below 30 mL/min/1.73 m2) are likely to be very sensitive to any further compromise of renal function, and there is no long-term clinical experience in these patients, the use of etoricoxib is not recommended in patients with advanced renal disease.