CSF leaks: correlation of high-resolution CT and multiplanar reformations with intraoperative endoscopic findings.

BACKGROUND AND PURPOSE: Skull base defects can result in CSF leaks, with meningitis as a potential complication. Surgeons are now routinely repairing these leaks via a nasal endoscopic approach. Accurate preoperative imaging is essential for surgical planning. A variety of imaging regimens have been employed, including axial and direct coronal CT, CT cisternography with iodinated contrast, radionuclide cisternography, and MR imaging. Now that multidetector helical CT is available, the purpose of this study was to determine how well coronal and sagittal multiplanar reformatted (MPR) images generated from a high-resolution axial dataset correlate with intraoperative findings in a group of patients with clinically proved CSF leaks. MATERIALS AND METHODS: We retrospectively reviewed imaging findings and surgical records of 19 patients who presented to our tertiary care institution during a 2.5-year period with clinically proved CSF leak. Patients underwent preoperative imaging with high-resolution helical CT (section collimation, 10 patients with 0.625-mm and 9 patients with 1.25-mm images), with MPR images processed by a neuroradiologist at a workstation. Two neuroradiologists, blinded to the intraoperative findings, determined the location and size of the skull base defects. All patients underwent endoscopic evaluation by an experienced sinonasal otolaryngologist, who confirmed the site of the CSF leak by direct inspection and measured the corresponding osseous defect. CT was considered accurate if it correctly localized the CSF leak and was within 2 mm of the endoscopic measurement. RESULTS: At endoscopy, 22 leaks of CSF were identified in 18 of 19 patients. CT correctly predicted the site of the leak in 20 (91%) of 22 cases and was accurate (within 2 mm of the endoscopic measurement) in 15 (75%) of 20 cases preoperatively localized. The CT measurement of the skull base defect differed from the endoscopic size in 5 (25%) of 20 cases, ranging from 7.4 mm below to 13 mm above the intraoperative measurement. When analysis was limited to the subgroup of 10 patients who had 0.625-mm axial images, the accuracy was improved, and of the 11 CSF leaks described at CT, all were verified at endoscopy. In addition, the submillimeter CT accurately measured the size of the osseous defect in 9 (82%) of 11 cases. In the remaining 2 (18%) of 11 cases, CT minimally overestimated the size of the osseous defect by only 3 mm. CONCLUSION: Axial images, and coronal, sagittal, and oblique MPR images generated from high-resolution axial CT performed well preoperatively, localizing the skull base defect responsible for the CSF leak. However, active manipulation of the axial dataset at a workstation is crucial in identifying and correctly describing these lesions. When submillimeter collimation is available, measurement of the osseous defects are accurate most of the time.

Induction of endothelial-leukocyte interaction by interferon-gamma requires coactivation of nuclear factor-kappaB.

To determine whether nuclear factor (NF)-kappaB is necessary to confer endothelial cell responsiveness to interferon (INF)-gamma in terms of vascular cell adhesion molecule (VCAM)-1 expression and leukocyte adhesion, human endothelial cells were treated with IFN-gamma in the presence of low concentrations (LCs) of interleukin (IL)-1alpha (

Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors.

BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) causes endothelial dysfunction in part by decreasing the availability of endothelial nitric oxide (NO). Although HMG CoA reductase inhibitors restore endothelial function by reducing serum cholesterol levels, it is not known whether they can also directly upregulate endothelial NO synthase (ecNOS) activity. METHODS AND RESULTS: Human saphenous vein endothelial cells were treated with ox-LDL (50 microg/mL thiobarbituric acid reactive substances 12 to 16 nmol/mg) in the presence of HMG CoA reductase inhibitors simvastatin and lovastatin. In a time-dependent manner, ox-LDL decreased ecNOS mRNA and protein levels (91+/-4% and 67+/-8% reduction after 72 hours, respectively). Both simvastatin (1 micromol/L) and lovastatin (10 micromol/L) upregulated ecNOS expression by 3.8-fold and 3.6-fold, respectively, and completely prevented its downregulation by ox-LDL. These effects of simvastatin on ecNOS expression correlated with changes in ecNOS activity. Although L-mevalonate alone did not affect ecNOS expression, cotreatment with L-mevalonate completely reversed ecNOS upregulation by simvastatin. Actinomycin D studies revealed that simvastatin stabilized ecNOS mRNA (tau1/2, 43 versus 35 hours). Nuclear run-on assays and transient transfection studies with a -1.6 kb ecNOS promoter construct showed that simvastatin did not affect ecNOS gene transcription. CONCLUSIONS: Inhibition of endothelial HMG CoA reductase upregulates ecNOS expression predominantly by posttranscriptional mechanisms. These findings suggest that HMG CoA reductase inhibitors may have beneficial effects in atherosclerosis beyond that attributed to the lowering of serum cholesterol by increasing ecNOS activity.

Hydrogen peroxide-mediated transcriptional induction of macrophage colony-stimulating factor by TGF-beta1.

TGF-beta1 and macrophages are important regulators of tissue fibrosis and remodeling. Here we show that TGF-beta1 induces the expression of macrophage-CSF (M-CSF) in vascular endothelial cells via a signaling pathway(s) involving hydrogen peroxide (H2O2). In a time-dependent manner, TGF-beta1 produced a 10- and a 6-fold increase in M-CSF mRNA and protein levels after 12 h, respectively. This increase in M-CSF expression was attenuated by a nitric oxide donor, S-nitrosoglutathione (GSNO), and by a nonspecific oxidase inhibitor, diphenylene iodonium. Furthermore, the TGF-beta1-induced M-CSF mRNA expression was inhibited by catalase, but not by superoxide dismutase, suggesting that H2O2 rather than superoxide anion (O2.-) is the primary mediator of the effects of TGF-beta1. Transient transfection studies using deletional M-CSF promoter constructs demonstrated that TGF-beta1 produced a 13-fold induction in M-CSF promoter activity that was repressed by >85% with GSNO and catalase, in part through inhibitory effects on kappaB cis-acting elements. Electrophoretic mobility shift assays revealed that the activation of nuclear factor-kappaB by TGF-beta1 was also inhibited by GSNO and catalase, but not by superoxide dismutase. In a concentration-dependent manner, treatment with exogenous H2O2 produced 14- and 4.6-fold increases in M-CSF promoter activity and mRNA expression, respectively. These results indicate that the generation of H2O2 and activation of NF-kappaB by TGF-beta1 are required for the induction of M-CSF gene transcription.