The association of leukocytes with secondary brain injury

Shock increases mortality from brain injuries, but the mechanism is poorly understood. We hypothesized that brain injury followed by shock and resuscitation leads to a secondary reperfusion injury mediated in part by polymorphonuclear leukocytes (PMNs). To validate this hypothesis, we studied cerebral perfusion pressure (CPP), intracranial pressure (ICP), cerebral blood flow (CBF), cortical water content (CWC), and hemodynamic variables in a porcine model of focal cryogenic brain injury and hemorrhagic shock. Cerebral PMN accumulation (CPMN) in the injured and uninjured hemispheres was determined histologically from the total PMNs in five high-power fields (400x). Twenty-nine mature swine were randomized to four groups. Group 1, the control group, was instrumented only. Group 2 animals had a brain injury alone and were studied for 24 hours. Group 3 animals had a brain injury and hemorrhagic shock. Group 4 animals had hemorrhagic shock alone. Brain injury followed by shock caused a significantly greater ICP and a significantly lower CBF than brain injury or shock alone. There was no significant difference in CPP between groups after resuscitation. The CWC of the lesioned area was similar in both brain-injured groups but was significantly increased when compared with the controls and the shock-only group. The CWC of the nonlesioned hemisphere was higher in group 3 than in group 2. The CPMN in both hemispheres in group 3 was significantly greater than in either group 2 or group 4. There was a significant positive correlation between CPMN and both ICP and CWC, and a significant negative correlation between CPMN and CBF. These data suggest an association between CPMN accumulation and secondary brain injury.     

Non-peptidic HIV protease inhibitors: C2-symmetry-based design of bis-sulfonamide dihydropyrones

Potent, non-peptidic, dihydropyrone sulfonamide HIV protease inhibitors have been previously described. Crystallographic analysis of dihydropyrone sulfonamide inhibitor/HIV protease complexes suggested incorporation of a second, C2 symmetry-related sulfonamide group. Selected bis-sulfonamide dihydropyrone analogues display high HIV protease inhibitory activity.     

Transmission-based scatter correction of 180 degrees myocardial single-photon emission tomographic studies

Meaningful comparison of single-photon emission tomographic (SPET) reconstructions for data acquired over 180 degrees or 360 degrees can only be performed if both attenuation and scatter correction are applied. Convolution subtraction has appeal as a practical method for scatter correction; however, it is limited to data acquired over 360 degrees. A new algorithm is proposed which can be applied equally well to data acquired over 180 degrees or 360 degrees. The method involves estimating scatter based on knowledge of reconstructed transmission data in combination with a reconstructed estimate of the activity distribution, obtained using attenuation correction with broad beam attenuation coefficients. Processing is implemented for planes of activity parallel to the projection images for which a simplified model for the scatter distribution may be applied, based on the measured attenuation. The appropriate broad beam (effective) attenuation coefficients were determined by considering the scatter buildup equation. It was demonstrated that narrow beam attenuation coefficients should be scaled by 0.75 and 0.65 to provide broad beam attenuation coefficients for technetium-99m and thallium-201 respectively. Using a thorax phantom, quantitative accuracy of the new algorithm was compared with conventional transmission-based convolution subtraction (TDCS) for 360 degrees data. Similar heart to lung contrasts were achieved and correction of 180 degrees data yielded a 10.4% error for cardiac activity compared to 5.2% for TDCS. Contrast for myocardium to ventricular cavity was similarly good for scatter-corrected 180 degrees and 360 degrees data, in contrast to attenuation-corrected data, where contrast was significantly reduced. The new algorithm provides a practical method for correction of scatter applicable to 180 degrees myocardial SPET.