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Biomedical subjects

Kyle D Weaver

Publications and source records attributed to Kyle D Weaver.

6 recordsLinked to original sources

Anterior endoscopic skull-base surgery getting started: an otolaryngologist's perspective.

PURPOSE OF REVIEW: Anterior endoscopic skull-base surgery is a relatively new field requiring new levels of cooperation between otolaryngology and neurosurgery. The formation of these teams is discussed along with their challenges. RECENT FINDINGS: A significant amount of literature has been produced in the last few years, chronicling new and innovative techniques for anterior endoscopic skull-base surgery. These techniques are requiring close coordination between otolaryngologist and neurosurgeon in a multidisciplinary approach. However, there are obstacles to overcome in forming these teams. SUMMARY: Anterior endoscopic skull-base surgery is a technically challenging skill set which requires multiple factors to perform successfully. Factors to overcome require surgical training, appropriate patient base, specialized equipment and institutional inertia. These obstacles may be overcome in the majority of centers.

Endoscopes↗

Methylated tumor-specific DNA as a plasma biomarker in patients with glioma.

OBJECTIVE: Patients with systemic malignancies have substantial quantities of tumor-specific DNA in their plasma which may serve as a potential biomarker for tumor burden. This approach has not been studied in gliomas. METHODS: Methylation specific polymerase chain reaction (MSP) was used to determine the methylation status the promoters for p16/(INK4a), MGMT, p73, and RARbeta within glioma tissue and plasma. Blood was collected prior to craniotomy in 10 patients with glioma. DNA was extracted from tumor and plasma samples and assayed with MSP. Total plasma DNA also was quantified. Tumor-specific plasma DNA was defined as identification of the same methylated promoter (MP) in both tumor and plasma. RESULTS: Total plasma DNA concentration was markedly elevated (mean 6,503 ng/ml, SEM 1,400 ng/ml). Glioma tissue contained methylation of at least one promoter in 9 out of 10 (90 percent) of patients studied. Of these patients, 6 out of 9 (67 percent) demonstrated methylation of at least one of the same promoters in plasma. Five of these had one MP identified in the plasma and one had 2 MP. Overall, glioma-specific plasma DNA was present in plasma of 6 out of 10 (60 percent) of patients. Each MP DNA marker found in the plasma also was present in the intracranial tumor. CONCLUSIONS: Patients with high grade gliomas have large amounts of DNA in the plasma. Of these primary brain tumors, 90 percent contained methylated gene promoters, and in over 60 percent of these patients the same methylated promoters present in the tumor also were found in the plasma. This represents the first step to developing a quantitative plasma biomarker that could be used to monitor glioma status.

Adult↗

Immunohistochemical analysis of metastatic neoplasms of the central nervous system.

Metastatic neoplasms to the central nervous system are often encountered in the practice of surgical neuropathology. It is not uncommon for patients with systemic malignancies to present to medical attention because of symptoms from a brain metastasis and for the tissue samples procured from these lesions to represent the first tissue available to study a malignancy from an unknown primary. In general surgical pathology, the evaluation of a metastatic neoplasm of unknown primary is a very complicated process, requiring knowledge of numerous different tumor types, reagents, and staining patterns. The past few years, however, have seen a remarkable refinement in the immunohistochemical tools at our disposal that now empower neuropathologists to take an active role in defining the relatively limited subset of neoplasms that commonly metastasize to the central nervous system. This information can direct imaging studies to find the primary tumor in a patient with an unknown primary, clarify the likely primary site of origin in patients who have small tumors in multiple sites without an obvious primary lesion, or establish lesions as late metastases of remote malignancies. Furthermore, specific treatments can begin and additional invasive procedures may be prevented if the neuropathologic evaluation of metastatic neoplasms provides information beyond the traditional diagnosis of "metastatic neoplasm." In this review, differential cytokeratins, adjuvant markers, and organ-specific antibodies are described and the immunohistochemical signatures of metastatic neoplasms that are commonly seen by neuropathologists are discussed.

Algorithms↗

A method to track cortical surface deformations using a laser range scanner.

This paper reports a novel method to track brain shift using a laser-range scanner (LRS) and nonrigid registration techniques. The LRS used in this paper is capable of generating textured point-clouds describing the surface geometry/intensity pattern of the brain as presented during cranial surgery. Using serial LRS acquisitions of the brain's surface and two-dimensional (2-D) nonrigid image registration, we developed a method to track surface motion during neurosurgical procedures. A series of experiments devised to evaluate the performance of the developed shift-tracking protocol are reported. In a controlled, quantitative phantom experiment, the results demonstrate that the surface shift-tracking protocol is capable of resolving shift to an accuracy of approximately 1.6 mm given initial shifts on the order of 15 mm. Furthermore, in a preliminary in vivo case using the tracked LRS and an independent optical measurement system, the automatic protocol was able to reconstruct 50% of the brain shift with an accuracy of 3.7 mm while the manual measurement was able to reconstruct 77% with an accuracy of 2.1 mm. The results suggest that a LRS is an effective tool for tracking brain surface shift during neurosurgery.

Algorithms↗

Potentiation of chemotherapeutic agents following antagonism of nuclear factor kappa B in human gliomas.

Future success using chemotherapy against human gliomas may result from exploiting unique molecular vulnerabilities of these tumors. Chemotherapy frequently results in DNA damage. When such damage is sensed by the cell, programmed cell death, or apoptosis, may be initiated. However, chemotherapy-induced DNA damage may activate nuclear factor kappa B (NF-kappaB) and block apoptosis. We inhibited NF-kappaB using a gene therapy approach to determine whether this would render human glioma cells more susceptible to chemotherapy. U87 and U251 glioma cell lines were infected with either treatment adenovirus containing the gene for a mutant non-degradable form of IkappaBalpha, which is an inhibitor of NF-kappaB nuclear translocation, or empty control virus. Following viral infection, cells were treated either with BCNU, carboplatin, tumor necrosis factor alpha (TNF-alpha), or SN-38. Chemotherapy resulted in a marked increase in active intranuclear NF-kappaB. This response was greatly decreased by insertion of the mutant repressor gene. Similarly, a significant increase in cell killing by all chemotherapy age was demonstrated following infection with treatment virus. Expression of the mutant repressor gene also resulted in increased apoptosis by TUNEL assay following chemotherapy. Numerous genes are responsible for glioma chemoresistance. DNA damage by chemotherapy may induce the antiapoptotic factor NF-kappaB and prevent programmed cell death. Insertion of a mutant inhibitor of NF-kappaB strips cells of this antiapoptotic defense and renders them more susceptible to killing by chemotherapy via increased apoptosis.

Adenoviridae↗

Successful transarterial Guglielmi detachable coil embolization of posttraumatic posterior communicating artery-cavernous sinus fistula: technical note.

OBJECTIVE: Carotid-cavernous fistulae are uncommon but well-documented sequelae of craniofacial trauma. A rare subset may arise from the posterior communicating artery instead of from the carotid artery proper. The presentation is similar to that of carotid-cavernous fistulae, with ocular pain, chemosis, and proptosis being the common symptoms. The first successful transarterial coil embolization of this type of lesion is described. METHODS: A 42-year-old man presented with severe craniocerebral injury, including multiple craniofacial fractures, after an industrial accident. He required emergent craniotomy for an open depressed cranial fracture and epidural hematoma. Six weeks after presentation, the patient began to exhibit progressive chemosis and proptosis. Magnetic resonance imaging revealed findings consistent with a carotid-cavernous fistula. RESULTS: Angiography revealed a fistula between the posterior communicating artery and the cavernous sinus. The origin of the fistula in the posterior communicating artery was successfully obliterated with Guglielmi detachable coiling. Subsequent studies demonstrated no flow through the fistula and good opacification of the ipsilateral posterior cerebral artery by the vertebrobasilar system. CONCLUSION: Posterior communicating artery-cavernous fistulae are a rare sequel of trauma. They may be treated successfully with the use of transarterial coil embolization.

Adult↗