The Group IVA cytosolic phospholipase A(2) (GIVA PLA(2)) is a particularly attractive target for drug development because it is the rate-limiting provider of proinflammatory mediators. We previously reported the discovery of novel 2-oxoamides that inhibit GIVA PLA(2) [Kokotos, G.; et al. J. Med. Chem. 2002, 45, 2891-2893]. In the present work, we have further explored this class of inhibitors and found that the 2-oxoamide functionality is more potent when it contains a long 2-oxoacyl residue and a free carboxy group. Long-chain 2-oxoamides based on gamma-aminobutyric acid and gamma-norleucine are potent inhibitors of GIVA PLA(2). Such inhibitors act through a fast and reversible mode of inhibition in vitro, are able to block the production of arachidonic acid and prostaglandin E(2) in cells, and demonstrate potent in vivo anti-inflammatory and analgesic activity.

This study assessed inter-and intrarater reliability and sensitivity to change of the 2-, 6-, and 12-minute walk tests following stroke. A convenience sample of patients enrolled in an inpatient stroke rehabilitation program participated in the standardization protocol. The 2-, 6-, and 12-minute walk tests were performed and inter-and intrarater reliability and responsiveness to change assessed. The interrater intraclass correlation coefficients (ICCs) for the 2-, 6-, and 12-minute walk tests were, respectively, 0.85, 0.78, and 0.68 (p < 0.0007 for each). The intrarater ICCs were 0.85, 0.74, and 0.71 (p < 0.0003 for each). Responsiveness to change as measured by standardized response mean (SRM) scores was, respectively, 1.34, 1.52, and 1.90 (F = 24.24, p < 0.001). Pearson correlations for the 2-, 6-, and 12-minute walk tests by the same rater on the same day were 2 versus 6 minutes, r = 0.997; 2 versus 12 minutes, r = 0.993; and 6 versus 12 minutes, r = 0.994 (p < 0.0001 for each). The 2-, 6-, and 12-minute walk tests show acceptable inter-and intrarater reliability and high intertest correlations when they are used for the assessment of walking following stroke. The SRM statistic indicates that the 12-minute walk test is the most responsive to change.

Donor variables correlated with CD34+ cell yield only weakly, so no particular clinical characteristic can be used to exclude an individual as a PBPC donor if he or she is otherwise suitable for the apheresis procedure.