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Biomedical subjects

Peter Jun

Publications and source records attributed to Peter Jun.

8 recordsLinked to original sources

Accuracy over space and time of computer-assisted fluoroscopic navigation in the lumbar spine in vivo.

OBJECTIVE: The integration of digital image-guided surgical navigation with C-arm fluoroscopy, known as virtual fluoroscopy (VF), has been shown to enhance the safety of spine surgery in vitro. Few clinical studies have assessed the accuracy of VF during actual spinal surgery, and no studies have investigated variations in accuracy over the course of a series of measurements obtained during operative cases. We sought to study the intraoperative accuracy of VF over time and space during lumbar pedicle screw placement in human patients. METHODS: Fluoroscopic images of the lumbar spine were obtained, calibrated, and saved to the Stealth Station (FluoroNav) on seven patients undergoing lumbar fusion surgery. The tracking arc was attached to an exposed lumbar spinous process, which was designated the index level. With use of anatomic surface irregularities in the laminae and spinous processes, several points were identified and registered on three different vertebrae directly adjacent to the index level vertebra. Every 15 minutes, throughout the operative case, the probe was brought to each point and the apparent distance from the original location recorded (as measured by the FluoroNav system). Measurements were collected from three vertebral levels adjacent to the index level over a time course of 120 minutes during the operation. RESULTS: At the index, index +1, index +2, and index +3 levels, 89%, 81%, 92%, and 64% of measurements were within <2 mm, whereas 97%, 96%, 97%, and 91% were within <3 mm, respectively. At 15, 30, 45, 60, 75, 90, 105, and 120 minutes, 96%, 89%, 85%, 61%, 85%, 90%, 93%, and 50% of measurements were within <2 mm, whereas 100%, 93%, 100%, 83%, 100%, 90%, 100%, and 100% of measurements were within <3 mm, respectively. The error in millimeters tended to increase as the distance from the index level increased (R = 0.19, P < 0.05) and as operative time increased (R = 0.26, P < 0.01). Calibration studies of intraoperative VF (IoVF) in the lumbar spine documented a reasonable degree of accuracy. The majority of sequential measurements obtained during IoVF in the lumbar spine were within an error range of <3 mm. CONCLUSIONS: Our results suggest that the use of VF is a reliable method of verifying the use of anatomic and/or radiographic landmarks for guidance during lumbar pedicle screw placement.

Adult↗

The supratonsillar approach to the inferior cerebellar peduncle: anatomy, surgical technique, and clinical application to cavernous malformations.

OBJECTIVE: To introduce the supratonsillar approach, an approach that traverses the tonsillobiventral fissure in a trajectory over the cerebellar tonsil to the inferior cerebellar peduncle, and to demonstrate the utility of this approach for resecting peduncular cavernous malformations. METHODS: Anatomy of the cerebellar tonsil and surrounding fissures, arteries, and veins are reviewed using cadaveric brain specimens. The surgical approach uses the three-quarter prone position, a suboccipital craniotomy, and wide splitting of the tonsillobiventral fissure. RESULTS: Of our experience with 171 patients with cavernous malformations, six patients had lesions in the inferior cerebellar peduncle that were resected using the supratonsillar approach. All cavernous malformations were removed completely and no patients experienced surgical complications or new deficits. CONCLUSION: The supratonsillar approach differs from the transvermian and telovelar approaches to the fourth ventricle, with a more superolateral trajectory that leads instead to the inferior cerebellar peduncle. By splitting the tonsillobiventral fissure and mobilizing the tonsil inferomedially, the point of access to the lesion is deepened and transgression of normal cerebellar tissue is minimized. This elegant approach is ideally suited to the removal of cavernous malformations.

Adult↗

Meningioma transcript profiles reveal deregulated Notch signaling pathway.

Meningiomas constitute the second most common central nervous system tumor, and yet relatively little is known about the molecular events that are important for the pathogenesis and malignant progression of these tumors. We have used serial analysis of gene expression to compare the transcriptomes of nonneoplastic meninges and meningiomas of all malignancy grades. A novel finding from this screen is the induction of three components of the Notch signaling pathway: the transcription factor, hairy and enhancer of Split1 (HES1) and two members of the Groucho/transducin-like enhancer of Split family of corepressors, TLE2 and TLE3. TLE corepressors interact and modulate the activity of a wide range of transcriptional regulatory systems, one of which is HES1. We have shown that the transcript and protein levels of HES1, the Notch2 and Notch1 receptors and the Jagged1 ligand are induced in meningiomas of all grades, whereas induction of TLE2 and TLE3 occurs specifically in higher-grade meningiomas. Meningioma cell lines express components of the Notch signaling pathway and an inhibitor of this pathway suppresses meningioma cell survival. These results suggest that deregulated expression of the Notch pathway is a critical event in meningioma pathogenesis and that modulation of this and potentially other signaling pathways by TLE corepressors leads to a more malignant phenotype.

Basic Helix-Loop-Helix Proteins↗

Epigenome analyses using BAC microarrays identify evolutionary conservation of tissue-specific methylation of SHANK3.

CpG islands are present in one-half of all human and mouse genes and typically overlap with promoters or exons. We developed a method for high-resolution analysis of the methylation status of CpG islands genome-wide, using arrays of BAC clones and the methylation-sensitive restriction enzyme NotI. Here we demonstrate the accuracy and specificity of the method. By computationally mapping all NotI sites, methylation events can be defined with single-nucleotide precision throughout the genome. We also demonstrate the unique expandability of the array method using a different methylation-sensitive restriction enzyme, BssHII. We identified and validated new CpG island loci that are methylated in a tissue-specific manner in normal human tissues. The methylation status of the CpG islands is associated with gene expression for several genes, including SHANK3, which encodes a structural protein in neuronal postsynaptic densities. Defects in SHANK3 seem to underlie human 22q13 deletion syndrome. Furthermore, these patterns for SHANK3 are conserved in mice and rats.

Animals↗

Shared epigenetic mechanisms in human and mouse gliomas inactivate expression of the growth suppressor SLC5A8.

Tumors arise in part from the deleterious effects of genetic and epigenetic mechanisms on gene expression. In several mouse models of human tumors, the tumorigenic phenotype is reversible, suggesting that epigenetic mechanisms also contribute significantly to tumorigenesis in mice. It is not known whether these are the same epigenetic mechanisms in human and mouse tumors or whether they affect homologous genes. Using an integrated approach for genome-wide methylation and copy number analyses, we identified SLC5A8 on chromosome 12q23.1 that was affected frequently by aberrant methylation in human astrocytomas and oligodendrogliomas. SLC5A8 encodes a sodium monocarboxylate cotransporter that was highly expressed in normal brain but was significant down-regulated in primary gliomas. Bisulfite sequencing analysis showed that the CpG island was unmethylated in normal brain but frequently localized methylated in brain tumors, consistent with the tumor-specific loss of gene expression. In glioma cell lines, SLC5A8 expression was also suppressed but could be reactivated with a methylation inhibitor. Expression of exogenous SLC5A8 in LN229 and LN443 glioma cells inhibited colony formation, suggesting that it may function as a growth suppressor in normal brain cells. Remarkably, 9 of 10 murine oligodendroglial tumors (from p53+/- or ink4a/arf+/- animals transgenic for S100beta-v-erbB) showed a similar tumor-specific down-regulation of mSLC5A8, the highly conserved mouse homologue. Taken together, these data suggest that SLC5A8 functions as a growth suppressor gene in vitro and that it is silenced frequently by epigenetic mechanisms in primary gliomas. The shared epigenetic inactivation of mSLC5A8 in mouse gliomas indicates an additional degree of commonality in the origin and/or pathway to tumorigenesis between primary human tumors and these mouse models of gliomas.

Animals↗

The sonographic features of papillary thyroid carcinomas: pictorial essay.

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy in children and adults, with an incidence of 22,000 cases per year in the United States. Differentiating PTC from more frequently occurring benign thyroid nodules has proved challenging as there may be significant overlap in their clinical presentation and sonographic appearance. That said, high-resolution ultrasound provides a safe and affordable way of identifying and characterizing thyroid nodules and guiding percutaneous biopsies. Although no single sonographic feature is pathognomonic for PTC, certain features should raise suspicion and the combination of several features may be even more suggestive. In this pictorial essay, we describe the high-resolution sonographic features of pathologically proven PTCs. The nodule number, echo texture, internal architecture, calcifications, margins, contours, vascularity, and lymph nodes are considered. While the classic sonographic description of PTC is a solitary, hypoechoic solid nodule with microcalcifications and intrinsic vascularity, in practice, PTC may manifest with a myriad of sonographic appearances making biopsy necessary for a definitive diagnosis.

Biopsy, Fine-Needle↗

Airbag deployment and improperly restrained children: a lethal combination.

BACKGROUND: Airbag deployment is an acknowledged mechanism of serious trauma in children involved in motor vehicle crashes. From a review of national databases, we determined the number and types of fatal and nonfatal injuries to children caused by airbag deployment and child restraint system use. We also reviewed the relevant literature and provide information useful for caregivers and health care professionals in hopes of reducing future injuries. METHODS: We retrospectively reviewed 263 reported cases in which airbag deployment caused fatal or nonfatal injuries in children from reports released by the National Highway and Transportation Safety Administration and the National Pediatric Trauma Registry. Data were collected from January 1993 to December 2002 and imported into a database program for analysis. RESULTS: Of the 263 pediatric injuries caused by airbag deployment, 159 were fatal, and 104 were nonfatal. The peak incidence occurred in 1998, when 58 children were reported injured. Head injuries were most frequent, involving 170 children (64.6%), followed by spinal injuries, involving 100 children (38.0%). For children in their first year of life, head injuries were the sole mechanism of fatality. Of all children studied, only six (2.3%) were properly restrained. CONCLUSION: Airbag deployment in motor vehicle crashes is a well-recognized mechanism of morbidity and mortality in the pediatric population. Most injuries include trauma to the head and spine, which can have significant long-term consequences. Although the reported incidence of such injuries is decreasing, many children are improperly restrained. In our study, only 2.3% of children were properly restrained, suggesting that proper child restraint and seating position could have prevented most injuries.

Accidents, Traffic↗

General principles in the medical and surgical management of spinal infections: a multidisciplinary approach.

OBJECT: Infections along the spinal axis are characterized by an insidious onset, and the resulting delays in diagnosis are associated with serious neurological consequences and even death. Infections of the spine can affect the vertebral bodies, intervertebral discs, spinal canal, and surrounding soft tissues. Neurological dysfunction occurs when the spinal cord becomes compressed, edematous, or ischemic due to compression by abscess or vascular compromise. The aim of this paper was to detail general diagnostic and management principles for this disease. METHODS: Recent progress in medical technologies, including the development of potent antimicrobial drugs, advanced imaging, and improved surgical methods, have dramatically reduced morbidity and mortality rates for spinal infections; however, debate still exists on the proper management of this disease. In this paper, the authors review the current management protocols for spinal infections at their institution, focusing on medical and surgical treatments for vertebral osteomyelitis, intervertebral disc space infections, and spinal canal and soft-tissue abscesses. CONCLUSIONS: Technological advances in imaging modalities, pharmaceutics, and surgery have resulted in excellent outcomes and have greatly reduced the morbidity and mortality rates associated with spinal infections. Currently, treatment of spinal infections requires a multidisciplinary team that includes infectious diseases experts, neuroradiologists, and spine surgeons. The key to successful management of spinal infections is early detection.

Bacterial Infections↗