Quality control in neurosurgery training

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41648/1/701_2003_Article_126.pd

Donald J. Reis, MD: Research Mentor Extraordinaire

Donald J. Reis, M.D., the late internationally reknowned neuroscientist, had a special talent for mentoring researchers early in their academic careers. His “hands-on” approach to laboratory investigation, his extraoridinary patience with novice researchers, his commitment to the scientific method, and his enthusiastic approach to the art of neuroscience all combined to make him the ideal mentor for many budding academics over the past four decades. The beauty of his scientific legacy is that he loved to each research. The following tribute is personal from one whose career was changed by a great mentor.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44283/1/10571_2004_Article_467228.pd

Quality control in neurosurgery training

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42455/1/31450241.pd

Increased leukotriene C 4 and vasogenic edema surrounding brain tumors in humans

Leukotrines are pharmacologically active compounds that promote vascular permeability. In this study we sought to determine whether tissue leukotriene–like immunoreactivity was increased in intracranial tumors associated with peritumoral edema. In 20 patients undergoing craniotomy tissue specimens were immediately frozen after removal and tissue leukotriene C 4 levels were determined by radioimmunoassay. An index of peritumoral edema was estimated from preoperative contrast-enhanced computed tomographic scans. There was a significant correlation between brain edema and tissue leukotriene levels ( p < 0.003). Metastatic tumors (n = 8) had the highest leukotriene C 4 level at 13.8 ± 8.5 pg/mg tissue (mean ± SE) and the highest index of edema 5.7 ± 1.8. The mean leukotriene C 4 level in the gliomas (n + 5) ws 6.2 ± 2.3 pg/mg tissue and the edema index was 2.1 ± 0.6. There was no edema and no neoplasma in he temporal lobes removed for seizure (n + 2), and their level of leukotriene C 4 was 0.4 ± 0.1 pg/mg tissue. The formation of leukotriene C 4 is stimulated by intracranial tumors. Leukotrienes increase blood–brain barrier permeability and may be important in the formation of vasogenic edema surrounding tumors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50315/1/410190613_ftp.pd

Glossopharyngeal schwannoma: review of five cases and the literature

Glossopharyngeal schwannomas are rare tumors in spite of the fact that acoustic schwannomas account for 8%-10% of intracranial tumors. There have been 23 reported cases in the literature. This report of five cases is the largest series of these tumors. The presentation, radiological workup, operation, and long-term postoperative results will be presented, along with a review of the literature.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29470/1/0000556.pd

Effect of intravenous eicosapentaenoic acid on cerebral blood flow, edema and brain prostaglandins in ischemic gerbils

Eicosapentaenoic acid is converted by cyclo-oxygenase to the prostacyclin, PGI3. Consequently eicosapentaenoic acid might protect the brain from the impairment in cerebral blood flow that follows temporary cerebral artirial occlusion. We studied the effect of 90% pure eicosapentaenoic acid, given intravenously, on cerebral blood flow, brain water and prostaglandins after ischemia in gerbils. Ischemia was produced by bilateral carotid occlusion for 15 min followed by reperfusion for 2 h. In experimental gerbils, 0.833 mg or 0.167 mg of eicosapentaenoic acid (Na salt) was given intravenously followed by a continuous infusion of 1 mg h-1. Control gerbils were given 0.167 mg of linoleic acid (Na salt) intravenously followed by a continuous infusion of 1 mg h-1 or a saline infusion. Regional cerebral blood flow was measured by the hydrogen clearance method and brain water by the specific gravity technique. Brain diene prostaglandins were measured by radioimmunoassay. In control gerbils cerebral blood flow decreased significantly during reperfusion and remained depressed after 2 h of reperfusion. In eicosapentaenoic acid treated gerbils blood flow decreased initially but after 2 h of reperfusion blood flow was significantly higher than in control gerbils. Brain edema and brain diene prostaglandins were not significantly different between control and experimental groups.Our study indicates that eicosapentaenoic acid, given intravenously, improves cerebral blood flow after ischemia and reperfusion. We speculate that this effect may be due to the formation of the prostacyclin, PGI3.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24690/1/0000109.pd

Management of anteriorly located C1-C2 neurofibromata

The authors discuss their recent experience with anteriorly located Cl-C2 neurofibromata in five patients with cervical myelopathy and magnetic resonance scans consistent with intradural extramedullary masses in this region. Surgery was performed using a posterolateral approach with microscopic intradural exploration. Gross total intradural tumor removal was achieved in all cases. Improvement in cervical myelopathy occurred in all patients.This report concludes that Cl-C2 neurofibromata located anterior to the spinal cord can be totally and safely removed using a posterolateral approach. Improvement in neurologic dysfunction accompanies posterior decompression and gross total intradural tumor removal.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28766/1/0000598.pd

Anterior cervical epidural abscess: The use of intraoperative spinal sonography

A case of acute cervical epidural abscess is presented. The use of intraoperative spinal sonography is discussed as a valuable adjunct in the evaluation and treatment of these uncommon lesions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26351/1/0000438.pd

The role of the coagulation cascade in brain edema formation after intracerebral hemorrhage

The coagulation cascade has a potential role in brain edema formation due to intracerebral hemorrhage. In this study blood and other solutions were injected stereotactically into the right basal ganglia in rats. Twenty-four hours following injection, brain water and ion contents were measured to determine the amount of brain edema. Intracerebral blood resulted in an increase in brain water content. The amount of brain edema surrounding the intracerebral hematoma was reduced by a thrombin inhibitor Na-(2-Naphthalenesulfonylglycyl)-4-amidino-DL-phenylalaninepiperidide, (α-NAPAP) infused into the hematoma after the clot had been allowed to solidify. The inhibitor did not alter the actual size of the clot mass. An artificial clot composed of fibrinogen, thrombin, and styrene microspheres also produced brain edema. A fibrin clot led to edema formation even in the absence of mass effect provided by the microspheres. The single component responsible for production of brain edema in all these models was thrombin. The edema was formed in response to a fibrinogen-independent pathway. These results indicate that the coagulation cascade is involved in brain edema that develops adjacent to an intracerebral hematoma.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41647/1/701_2005_Article_BF01420301.pd

The role of GLI-SOX2 signaling axis for gemcitabine resistance in pancreatic cancer

Pancreatic cancer, mostly pancreatic ductal adenocarcinomas (PDAC), is one of the most lethal cancers, with a dismal median survival around 8 months. PDAC is notoriously resistant to chemotherapy. Thus far, numerous attempts using novel targeted therapies and immunotherapies yielded limited clinical benefits for pancreatic cancer patients. It is hoped that delineating the molecular mechanisms underlying drug resistance in pancreatic cancer may provide novel therapeutic options. Using acquired gemcitabine resistant pancreatic cell lines, we revealed an important role of the GLI-SOX2 signaling axis for regulation of gemcitabine sensitivity in vitro and in animal models. Down-regulation of GLI transcriptional factors (GLI1 or GLI2), but not SMO signaling inhibition, reduces tumor sphere formation, a characteristics of tumor initiating cell (TIC). Down-regulation of GLI transcription factors also decreased expression of TIC marker CD24. Similarly, high SOX2 expression is associated with gemcitabine resistance whereas down-regulation of SOX2 sensitizes pancreatic cancer cells to gemcitabine treatment. We further revealed that elevated SOX2 expression is associated with an increase in GLI1 or GLI2 expression. Our ChIP assay revealed that GLI proteins are associated with a putative Gli binding site within the SOX2 promoter, suggesting a more direct regulation of SOX2 by GLI transcription factors. The relevance of our findings to human disease was revealed in human cancer specimens. We found that high SOX2 protein expression is associated with frequent tumor relapse and poor survival in stage II PDAC patients (all of them underwent gemcitabine treatment), indicating that reduced SOX2 expression or down-regulation of GLI transcription factors may be effective in sensitizing pancreatic cancer cells to gemcitabine treatment