Faculty Bibliography

Platelet activating factor (PAF) enhances polymorphonuclear leukocyte (PMN) superoxide (.O2-) production, CD11b expression, and elastase release, all essential components in the pathophysiology of multiple-organ failure. This study was designed to determine the effects of Lexipafant, a PAF receptor antagonist, on PAF-mediated PMN functions. PMNs from 10 healthy volunteers were isolated and pretreated with various concentrations of Lexipafant (0-100 microM). PMNs were then incubated for 5 min with 200 nM PAF for .O2- detection or 2000 nM PAF for elastase measurement and activated with 1 microM N-formylmethionylleucylphenylalanine. The mean rate of .O2- production was determined by a cytochrome c reduction assay (nmole .O2-/min/1.33 x 10(5) PMN +/- SEM). Elastase release was measured by the cleavage of the synthetic elastase substrate Meo-Suc-Ala-Ala-Pro-Val-pNA (mean elastolytic activity +/- SEM). In parallel experiments, PMNs were incubated with 200 nM PAF for 30 min following pre-treatment with Lexipafant and CD11b expression was determined by flow cytometry (mean fluorescence intensity +/- SEM). Statistical analysis was performed using repeated-measures ANOVA (P < 0.05). Lexipafant inhibited PAF-enhanced PMN .O2- generation, CD11b expression and elastase release in a dose dependent fashion. The IC50 of Lexipafant for .O2- production, CD11b expression, and elastase release was 0.046, 0.285, and 0.05 microM, respectively. Lexipafant attenuated the PAF-mediated upregulation of PMN .O2- production, CD11b expression, and elastase release in a dose dependent fashion. These data support the hypothesis that Lexipafant may reduce the severity of the inflammatory response to injury produced by PAF-enhanced activation of PMNs

PURPOSE: To evaluate gadolinium-enhanced three-dimensional magnetic resonance (MR) angiography for thoracic aortic disease and to compare this technique with conventional thoracic MR imaging. MATERIALS AND METHODS: One hundred eight consecutive patients underwent 122 thoracic MR examinations, including conventional MR imaging followed by enhanced three-dimensional MR angiography. A gradient-echo sequence was used at 1.5 T (116 examinations) and 1.0 T (6 examinations) during infusion of 0.2 mmol/kg gadopentetate dimeglumine. Two independent readers (A and B), with varied experience in thoracic MR angiography, retrospectively evaluated the images for presence of aortic dissection, aneurysm, arch vessel disease, and protruding atheroma. Correlation with findings of surgery or other imaging modalities was available in 98 cases. RESULTS: Enhanced MR angiography was sensitive (92%-96%) and specific (100%) for acute and chronic aortic dissection (n = 26) and was as useful as conventional MR imaging in the diagnosis of aneurysm (n = 43) and arch vessel disease (n = 7). One of two intramural hematomas were overlooked at MR angiography by reader A, and both were overlooked by reader B. CONCLUSION: Enhanced three-dimensional MR angiography is a rapid and accurate imaging modality in diagnosis of thoracic aortic disease but is insensitive to intramural hematoma

BACKGROUND: A variety of surgical techniques has been developed to attempt to minimize the risk of paraplegia after descending thoracic aortic aneurysm repair. This study reviews our institutional experience with several basic techniques over a period of 10 years. METHODS: Seventy-eight consecutive patients underwent repair of descending thoracic aortic aneurysm between 1983 and 1993. Two basic repair strategies were used: (1) distal perfusion with somatosensory evoked potential monitoring (n = 54) and (2) cross-clamping (n = 24), alone (n = 6) or with controlled distal exsanguination (n = 18). RESULTS: The operative mortality rate was 6.5% for elective repair (n = 62), 25.0% for emergent repair (n = 16), and 10.3% overall. Univariate predictors of increased operative risk were emergent operation, rupture, and shock. Neither death nor paraplegia was related to the operative technique used. The incidence of paraplegia was 3.7% in perfused patients and 4.2% in cross-clamping patients (p > 0.05). Paraplegia did not occur after any elective operation (zero of 62) but occurred in 18.6% of emergent cases (p < 0.01). In perfused patients, paraplegia did not occur when the distal pressure was maintained above 55 mm Hg and somatosensory evoked potentials remained intact. When somatosensory evoked potentials were lost (n = 7) in perfused patients, the operative technique was altered successfully in 5 patients, whereas in 2 patients (28.6%), paraplegia developed. CONCLUSIONS: The risks associated with elective descending thoracic aortic aneurysm repair were extremely low using an operative strategy that was flexible but skewed toward perfusion with somatosensory evoked potential monitoring. In perfused patients, paraplegia did not occur when distal pressure was greater than 55 mm Hg and somatosensory evoked potentials remained intact. However, the risks of death and paraplegia were primarily related to emergent presentation, not to technique, and the technique of cross clamping with controlled distal exsanguination was found to be valuable in unstable or in anatomically complicated subsets of patients