Incidence and risk factors for pulmonary exacerbation treatment failures in cystic fibrosis patients chronically infected with Pseudomonas aeruginosa

Background: Pulmonary exacerbations (PEx) are responsible for much of the morbidity and mortality associated with cystic fibrosis (CF). However, there is a paucity of data on outcomes in CF PEx and factors influencing outcomes.

Methods: We reviewed all PEx in patients infected with Pseudomonas aeruginosa treated with parenteral antibiotics over 4 years at our center. Treatment failures were categorized a priori as those PEx requiring antibiotic regimen change, prolongation of therapy > 20 days because of failure to respond, an early recurrent event within < 45 days, or failure to recover lung function to > 90% of baseline FEV1.

Results: A total of 101 patients were followed for 452 PEx. Treatment failures were observed in 125 (28%) of PEx; antibiotic regimen change was observed in 27 (6%), prolongation of therapy in 29 (6%), early recurrent events in 63 (14%), and failure to recover lung function to > 90% of baseline FEV1 in 66 (15%). Demographic factors associated with one or more treatment failures per year included advanced airways disease, use of enteric feeds, CF-related diabetes, and CF liver disease but did not include female sex or F508del homozygosity. Increased treatment failure risk was associated with lower admission FEV1 and increased markers of inflammation. At therapeutic completion, increased inflammatory markers correlated with treatment failure. Failure rates decreased with increasing number of active antimicrobial agents used based on in vitro susceptibility (zero, 28/65 [43%]; one, 38/140 [27%]; two, 59/245 [24%]; three, 0/2 [0%]; P = .02).

Conclusions: One-fourth of PEx fail to respond adequately to initial management. Patient demographic and episode-specific clinical information can be used to identify individuals at increased risk of initial management failure.

Adventures in the pharmacological analysis of P2 receptors

The pharmacological classification of P2 receptors owes its origin to the pioneering efforts of Geoff Burnstock and those who followed him, research that was conducted primarily in physiological experimental systems. Over recent years, the techniques of molecular biology have been increasingly applied in the study of P2 receptors while, at the same time, advances in their pharmacological analysis have been limited by a lack of potent and selective agonist or antagonist ligands. This has resulted in a classification scheme which is largely structural in nature, with relatively little contribution from pharmacology. Our endeavours in this area have been directed towards the discovery of ligands with which the pharmacological analysis and definition of P2 receptors could be advanced, the ultimate goal being the design of therapeutic agents. This article will describe some of our experiences in this challenging but rewarding Nea. (C) 2000 Elsevier Science B.V. All rights reserved.

ADP can induce aggregation of human platelets via both P2Y(1) and P-2T receptors

1 In the present study we have investigated the roles of P2Y(1) and P-2T receptor subtypes in adenosine 5'-diphosphate (ADP)-induced aggregation of human platelets in heparinized platelet rich plasma.

Biaxial Deformation and Experimental Study of PET at Conditions Applicable to Stretch Blow Molding

This article is concerned with understanding the behavior of polyethylene terephthalate (PET) in the injection stretch blow molding (ISBM) process where it is typically biaxially stretched to form bottles for the packaging industry. A comprehensive experimental study was undertaken, analyzing the behavior of three different grades of PET under constant width (CW), simultaneous (EB), and sequential (SQ) equal biaxial deformation. Experiments were carried out at temperature and strain rate ranges of 80–110C and 1 /s to 32 /s, respectively, to different stretch ratios. Results show that the biaxial deformation behavior of PET exhibits a strong dependency on forming temperature, strain rate, stretch ratio,deformation mode, and molecular weight. The tests were also monitored via a high speed thermal image camera which showed an increase in temperature between 5C and 15C observed depending on the stretch conditions.

Experimental Investigation of Stretch Blow Molding, Part 2: Analysis of Process Variables, Blowing Kinematics, and Bottle Properties

The work presented in this paper takes advantage of newly developed instrumentation suitable for in process monitoring of an industrial stretch blow molding machine. The instrumentation provides blowing pressure and stretch rod force histories along with the kinematics of polymer contact with the mould wall. A Design of Experiments pattern was used to qualitatively relate machine inputs with these process parameters and the thickness distribution of stretch blow molded PET (polyethylene terephtalate) bottles. Material slippage at the mold wall and thickness distribution is also discussed in relation to machine inputs. The key process indicators defined have great potential for use in a closed loop process control system and for validation of process simulations.

Assembly of a coordination cage with four aromatic channel receptors on the outside

Silver salts and triphosphine ligands with biphenyl substituents assemble to give coordination cages with four external aromatic channel receptors in a pseudo-tetrahedral arrangement.