RESUMEN
BACKGROUND AND PURPOSE: Malignant electroencephalography patterns are considered predictive of poor outcome in comatose survivors of cardiac arrest. We hypothesized that malignant patterns on electroencephalography are associated with evidence of more severe brain injury on MR imaging. MATERIALS AND METHODS: Retrospective review of clinical, imaging, and electroencephalography data of 33 adult comatose survivors of cardiac arrest following therapeutic hypothermia was performed. Outcomes measured included discharge destination and survival. Imaging studies were visually scored for severity of brain injury. Mean whole-brain apparent diffusion coefficient and percentage of severely injured brain (ADC < 700 × 10-6 mm2/s) were calculated. Continuous electroencephalographic interpretation was characterized as malignant or nonmalignant. Nonparametric tests were performed to assess the relationship of patient outcome, MR imaging, and electroencephalography patterns. RESULTS: Subjects with anatomic evidence of diffuse brain injury were less likely to have malignant electroencephalography patterns. Subjects with malignant electroencephalography patterns, invariably associated with bad outcomes, were observed to have whole-brain apparent diffusion coefficient measures similar to those in subjects with nonmalignant electroencephalography patterns and good outcome and different from those in subjects with nonmalignant electroencephalography patterns and bad outcomes. Regional hippocampal or basal ganglia injury was associated with a bad outcome regardless of electroencephalography findings. CONCLUSIONS: We found discordant evidence of brain injury by MR imaging and electroencephalography, refuting our initial hypothesis. Malignant electroencephalography patterns were generally more frequent in subjects with less severe brain injury by MR imaging. These findings suggest a complementary role of MR imaging and electroencephalography and support the aggressive treatment of malignant electroencephalography patterns in this population.
RESUMEN
alpha(2)-Macroglobulin (alpha(2)M) functions as a proteinase inhibitor and as a carrier of diverse growth factors. In this study, we localized binding sites for platelet-derived growth factor-BB (PDGF-BB) and nerve growth factor-beta (NGF-beta) to a linear sequence in the 180-kDa human alpha(2)M subunit which includes amino acids 591-774. A glutathione S-transferase fusion protein containing amino acids 591-774 (FP3) bound PDGF-BB and NGF-beta in ligand blotting assays whereas five other fusion proteins, which collectively include amino acids 99-590 and 775-1451 did not. The K(D) values for PDGF-BB and NGF-beta binding to immobilized FP3 were 300 +/- 40 and 180 +/- 30 nM, respectively; these values were comparable with those determined using methylamine-modified alpha(2)M, suggesting that higher-order alpha(2)M structure is not necessary for PDGF-BB and NGF-beta binding. PDGF-BB and NGF-beta blocked the binding of transforming growth factor-beta1 (TGF-beta1) to FP3. Furthermore, murinoglobulin, which is the only known member of the alpha-macroglobulin family that does not bind TGF-beta, also failed to bind PDGF-BB and NGF-beta. These results support the hypothesis that either a single linear sequence in human alpha(2)M or overlapping sequences are responsible for the binding of TGF-beta, PDGF-BB, and NGF-beta, even though there is minimal sequence identity between these three growth factors. FP3 blocked the binding of PDGF-BB to a purified chimeric protein, in which the extracellular domain of the PDGF beta receptor was fused to the IgG(1) Fc domain, and to PDGF receptors on NIH 3T3 cells. Thus, FP3 may inhibit the activity of PDGF-BB.