1999 Media Guide

1999 Men\u27s Track and Field Media Guide, George Fox College

Genome-wide and gene-specific epigenomic platforms for hepatocellular carcinoma biomarker development trials

The majority of the epigenomic reports in hepatocellular carcinoma have focused on identifying novel differentially methylated drivers or passengers of the oncogenic process. Few reports have considered the technologies in place for clinical translation of newly identified biomarkers. The aim of this study was to identify epigenomic technologies that need only a small number of samples to discriminate HCC from non-HCC tissue, a basic requirement for biomarker development trials. To assess that potential, we used quantitative Methylation Specific PCR, oligonucleotide tiling arrays, and Methylation BeadChip assays. Concurrent global DNA hypomethylation, gene-specific hypermethylation, and chromatin alterations were observed as a hallmark of HCC. A global loss of promoter methylation was observed in HCC with the Illumina BeadChip assays and the Nimblegen oligonucleotide arrays. HCC samples had lower median methylation peak scores and a reduced number of significant promoter-wide methylated probes. Promoter hypermethylation of RASSF1A, SSBP2, and B4GALT1 quantified by qMSP had a sensitivity ranging from 38% to 52%, a specificity of 100%, and an AUC from 0.58 to 0.75. A panel combining these genes with HCC risk factors had a sensitivity of 87%, a specificity of 100%, and an AUC of 0.91

Genome-Wide and Gene-Specific Epigenomic Platforms for Hepatocellular Carcinoma Biomarker Development Trials

The majority of the epigenomic reports in hepatocellular carcinoma have focused on identifying novel differentially methylated drivers or passengers of the oncogenic process. Few reports have considered the technologies in place for clinical translation of newly identified biomarkers. The aim of this study was to identify epigenomic technologies that need only a small number of samples to discriminate HCC from non-HCC tissue, a basic requirement for biomarker development trials. To assess that potential, we used quantitative Methylation Specific PCR, oligonucleotide tiling arrays, and Methylation BeadChip assays. Concurrent global DNA hypomethylation, gene-specific hypermethylation, and chromatin alterations were observed as a hallmark of HCC. A global loss of promoter methylation was observed in HCC with the Illumina BeadChip assays and the Nimblegen oligonucleotide arrays. HCC samples had lower median methylation peak scores and a reduced number of significant promoter-wide methylated probes. Promoter hypermethylation of RASSF1A, SSBP2, and B4GALT1 quantified by qMSP had a sensitivity ranging from 38% to 52%, a specificity of 100%, and an AUC from 0.58 to 0.75. A panel combining these genes with HCC risk factors had a sensitivity of 87%, a specificity of 100%, and an AUC of 0.91

Ocular cranial nerve palsies secondary to sphenoid sinusitis

Objective: The clinical presentation of sphenoid sinusitis can be highly variable. Rarely, sphenoid sinusitis may present with cranial nerve complications due to the proximity of these structures to the sphenoid sinus. Method: A case series from Rabin Medical Center and all cases of cranial nerves palsies secondary to sphenoid sinusitis that have been reported in the literature were reviewed. Results: Seventeen patients were identified. The abducent nerve was the most common cranial nerve affected (76%), followed by the oculomotor nerve (18%). One patient had combined oculomotor, trochlear and abducent palsies. The most common pathology was isolated purulent sphenoid sinusitis in 64% followed by allergic fungal sinusitis (AFS) in 18%, and fungal infection in 18%. 94% had an acute presentation. The majority (85%) received a combined intravenous antibiotics and surgical treatment. The remainder received conservative treatment alone. Complete recovery of cranial nerve palsy was noted in 82% during follow up. Conclusion: Sphenoid sinusitis presenting as diplopia and headaches is rare. A neoplastic process must be ruled out and early surgical intervention with intravenous antimicrobial therapy carry an excellent outcome with complete resolution of symptoms. Keywords: Sphenoid, Sinusitis, Sphenoiditis, Ocular, Cranial nerve, Pals

A prospective, feasibility study to evaluate the efficacy and usability of a novel drivable endoscope in patients with chronic rhinosinusitis

Purpose To carry out a pilot study to evaluate the efficacy of a novel, drivable endoscope (the Peregrine (TM) Drivable ENT Scope), compared to standard rigid endoscopes in the access, visualization, and irrigation of the paranasal sinus anatomy. Methods A prospective, multi-center, feasibility study was conducted on seventeen subjects who underwent primary functional endoscopic sinus surgery and were evaluated with the drivable endoscope and standard, rigid endoscopes (0 degrees, 30 degrees and 70 degrees, as applicable). A CT scan was available for image guidance, as needed. The primary efficacy endpoint was the ability to access and visualize sinonasal anatomic landmarks. Secondary endpoints included device usability, as measured by a usability questionnaire given to surgeons postoperatively; the device's ability to irrigate the sinuses and patient reports of tolerability and pain during postoperative procedures. Results The drivable endoscope success rate in visualizing all paranasal sinus anatomic landmarks was 55.6% better than the standard rigid endoscopes: 98.3% (178/181) versus 42.7% (76/178); p < 0.001. Surgeons rated scores of over 4 (on a 1-5 scale) for the usability of the drivable endoscope to enter the maxillary, frontal and sphenoid sinuses. The ability to irrigate the sinuses using the drivable endoscope was given a mean score of 4.3, and image quality was given a mean score of 3.4. The three patients evaluated postoperatively reported low pain and high tolerability scores with the drivable endoscope. Conclusions These preliminary results indicate that the drivable endoscope is effective, easy to use and highly tolerable in sinonasal endoscopy

Spontaneous sphenoid wing meningoencephaloceles with lateral sphenoid sinus extension: the endoscopic transpterygoid approach.

Spontaneous meningoencephalocele (SME) of the sphenoid wing is a rare cause of cerebrospinal fluid (CSF) leakage. Surgical closure of the fistula is usually required. The approach taken depends on the location of the defect and the extension of the meningoencephalocele. The endoscopic transpterygoid approach may be useful. We prospectively analyzed the three cases of SME of the sphenoid wing with lateral sphenoid sinus extension treated endoscopically at Stanford over the last 3 years with regard to imaging findings, operative technique, and operative morbidity. In our three cases, the extent of pterygopalatine fossa (PPF) exposure undertaken, complete in one and partial in two, depended on the defect site. Follow-up ranged from 17 to 25 months. The fistula was completely closed in all three cases. Extant literature reports a 97% rate of successful closure (N = 65 of 67, with a mean follow-up of 25 months) and no major complications. Endoscopic transpterygoid repair is a useful, safe alternative to traditional approaches for repair of SME of the sphenoid wing. Its feasibility depends on the site of the defect, which can be identified by preoperative imaging. Larger PPF exposure and postoperative lumbar drainage of CSF can be useful and have a low risk of morbidity

Spontaneous Sphenoid Wing Meningoencephaloceles with Lateral Sphenoid Sinus Extension: The Endoscopic Transpterygoid Approach

Spontaneous meningoencephalocele (SME) of the sphenoid wing is a rare cause of cerebrospinal fluid (CSF) leakage. Surgical closure of the fistula is usually required. The approach taken depends on the location of the defect and the extension of the meningoencephalocele. The endoscopic transpterygoid approach may be useful. We prospectively analyzed the three cases of SME of the sphenoid wing with lateral sphenoid sinus extension treated endoscopically at Stanford over the last 3 years with regard to imaging findings, operative technique, and operative morbidity. In our three cases, the extent of pterygopalatine fossa (PPF) exposure undertaken, complete in one and partial in two, depended on the defect site. Follow-up ranged from 17 to 25 months. The fistula was completely closed in all three cases. Extant literature reports a 97% rate of successful closure (N = 65 of 67, with a mean follow-up of 25 months) and no major complications. Endoscopic transpterygoid repair is a useful, safe alternative to traditional approaches for repair of SME of the sphenoid wing. Its feasibility depends on the site of the defect, which can be identified by preoperative imaging. Larger PPF exposure and postoperative lumbar drainage of CSF can be useful and have a low risk of morbidity

Prenatal exposure to tobacco smoke leads to increased mitochondrial DNA content in umbilical cord serum associated to reduced gestational age

<p>We investigated if prenatal exposures to tobacco smoke lead to changes in mitochondrial DNA content (mtDNA) in cord serum and adversely affect newborns’ health. Umbilical cord serum cotinine levels were used to determine in utero exposure to smoking. Cord serum mtDNA was measured by quantitative polymerase chain reaction analysis of the genes coding for cytochrome c oxidase1 (<i>MT</i>-<i>CO1</i>) and cytochrome c oxidase2 (<i>MT</i>-<i>CO2</i>). Log transformed levels of mtDNA coding for <i>MT</i>-<i>CO1</i> and <i>MT</i>-<i>CO2</i> were significantly higher among infants of active smokers with higher serum level of cotinine (<i>p</i> < 0.05) and inversely associated with gestational age (<i>p</i> = 0.08; <i>p</i> = 0.02). Structural equation modeling results confirmed a positive association between cotinine and <i>MT</i>-<i>CO1</i> and2 (<i>p</i> < 0.01) and inverse associations with gestational age (<i>p</i> = 0.02) and <i>IGF</i>-<i>1</i> (<i>p</i> < 0.01). We identified a dose-dependent increase in the level of <i>MT</i>-<i>CO1</i> and <i>MT</i>-<i>CO2</i> associated to increased cord serum cotinine and decreased gestational age.</p

Clinical and public health research using methylated DNA immunoprecipitation (MeDIP) A comparison of commercially available kits to examine differential DNA methylation across the genome

The methylated DNA immunoprecipitation method (MeDIP) is a genome-wide, high-resolution approach that detects DNA methylation with oligonucleotide tiling arrays or high throughput sequencing platforms. A simplified high-throughput MeDIP assay will enable translational research studies in clinics and populations, which will greatly enhance our understanding of the human methylome. We compared three commercial kits, MagMeDIP Kit TM (Diagenode), Methylated-DNA IP Kit (Zymo Research) and Methylamp (TM) Methylated DNA Capture Kit (Epigentek), in order to identify which one has better reliability and sensitivity for genomic DNA enrichment. Each kit was used to enrich two samples, one from fresh tissue and one from a cell line, with two different DNA amounts. The enrichment efficiency of each kit was evaluated by agarose gel band intensity after Nco I digestion and by reaction yield of methylated DNA. A successful enrichment is expected to have a 1:4 to 10:1 conversion ratio and a yield of 80% or higher. We also evaluated the hybridization efficiency to genome-wide methylation arrays in a separate cohort of tissue samples. We observed that the MagMeDIP kit had the highest yield for the two DNA amounts and for both the tissue and cell line samples, as well as for the positive control. In addition, the DNA was successfully enriched from a 1:4 to 10:1 ratio. Therefore, the MagMeDIP kit is a useful research tool that will enable clinical and public health genome-wide DNA methylation studies