Recombinant human platelet-activating factor acetylhydrolase for treatment of severe sepsis: results of a phase III, multicenter, randomized, double-blind, placebo-controlled, clinical trial.

Objective: Platelet-activating factor (PAF) and structurally-related oxidized phospholipids are proinflammatory mediators in systemic inflammatory states such as severe sepsis. The enzyme platelet-activating factor acetylhydrolase (PAF-AH) rapidly degrades PAF and oxidized phospholipids into inactive metabolites. Reduced PAF-AH activity has been observed in patients with severe sepsis and may contribute to their systemic inflammatory response and organ dysfunction.

Multiple-center, randomized, placebo-controlled, double-blind study of the nitric oxide synthase inhibitor 546C88: effect on survival in patients with septic shock.

Objective: To assess the safety and efficacy of the nitric oxide synthase inhibitor 546C88 in patients with septic shock. The predefined primary efficacy objective was survival at day 28.

Design: Multiple-center, randomized, two-stage, double-blind, placebo-controlled, safety and efficacy study.

Cardiovascular effects of the nitric oxide synthase inhibitor NG-methyl-L-arginine hydrochloride (546C88) in patients with septic shock: results of a randomized, double-blind, placebo-controlled multicenter study (study no. 144-002).

Objective: To assess the hemodynamic effects of the nitric oxide synthase inhibitor 546C88 in patients with septic shock, although this was not a stated aim of the protocol. The predefined primary efficacy objective of the protocol was resolution of shock determined at the end of a 72-hr treatment period.

Design: Multicentered, randomized, placebo-controlled, safety and efficacy study.

Drotrecogin alfa (activated) (recombinant human activated protein C) reduces host coagulopathy response in patients with severe sepsis.

Drotrecogin alfa (activated) improved survival in patients with severe sepsis in PROWESS, a double-blind, study of 1690 adult patients randomized to drotrecogin alfa (activated) at 24 microg/kg/h (N=850) or placebo (N=840) infused for 96 hours. Pharmacodynamic effects of drotrecogin alfa (activated) were assessed with 15 prospectively defined systemic biomarkers of hemostasis, inflammation and endothelial injury. The last-observation-carried-forward (LOCF) method of imputation for missing observations was the prospectively defined statistical method.

The 2000-2001 GEP-ISFG Collaborative Exercise on mtDNA: assessing the cause of unsuccessful mtDNA PCR amplification of hair shaft samples.

We report the results of Spanish and Portuguese working group (GEP) of International Society of Forensic Genetics (ISFG) Collaborative Exercise 2001-2002 on mitochondrial DNA (mtDNA) analysis. 64 laboratories from Spain, Portugal and several Latin-American countries participated in this quality control exercise. Five samples were sent to the participating laboratories, four blood stains (M1-M4) and a sample (M5) consisting of two hair shaft fragments.

Interaction between hemoglobin and glutathione in the regulation of blood flow in normal and septic pigs.

Background: Hemoglobin (Hb) induces vasoconstriction by heme group binding nitric oxide in an irreversible fashion. Recent in vitro studies indicate that the thiol groups in Hb reversibly bind nitric oxide and participate in trans-nitrosylation reactions with other thiols. Sepsis is a pathophysiologic state characterized by vasodilation mediated, at least in part, by an excessive release of nitric oxide.

Hemiscrotectomy with contralateral testicular transposition for scrotal cancer.

Purpose: Wide excision of scrotal tumors results in serious defects to such an extent that in some cases the contents of the scrotum cannot be preserved. We describe a hemiscrotectomy technique with transposition of the testis to the contralateral hemiscrotum that facilitates closure of the surgical wound and allows preservation of the testis.

Materials And Methods: Our procedure was used in 3 patients with scrotal neoplasia, including 2 with squamous cell carcinoma and 1 with extramammary Paget's disease.

Results of the 1999-2000 collaborative exercise and proficiency testing program on mitochondrial DNA of the GEP-ISFG: an inter-laboratory study of the observed variability in the heteroplasmy level of hair from the same donor.

The Spanish and Portuguese working group (GEP) of international society for forensic genetics (ISFG) 1999-2000 collaborative exercise on mitochondrial DNA (mtDNA) included the analysis of four bloodstain samples and one hair shaft sample by 19 participating laboratories from Spain, Portugal and several Latin-American countries. A wide range of sequence results at position 16,093 of the HV1 (from T or C homoplasmy to different levels of heteroplasmy) were submitted by the different participating laboratories from the hair shaft sample during the first phase of this exercise. During the discussion of these results in the Annual GEP-ISFG 2000 Conference a second phase of this exercise was established with two main objectives: (i) to evaluate the incidence of the HV1 sequence heteroplasmy detected in Phase I across different sample types from the same donor including blood, saliva, and hair shafts, (ii) to perform a technical review of the electropherograms to evaluate the relative levels of heteroplasmies obtained by the different laboratories and also to examine the source of possible errors detected in Phase I.

Increase of bone alkaline phosphatase after androgen deprivation therapy in patients with prostate cancer.

Objectives: To evaluate the behavior of bone alkaline phosphatase (BAP) after androgen deprivation therapy in patients with prostate cancer.

Methods: BAP was determined in the serum of 35 patients with nonmetastatic prostate cancer before maximal androgen blockade. During 5 years of follow-up, BAP was determined annually.