bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNAi Supress VEGF, TERT, and Bcl‐xl in HEp‐2 Cells
Authors: Tao Ze‐Zhang , Yan Wang 
Published: August 2008

ProblemTo develop an RNA‐interference (RNAi) approach involving the hitting of multiple targets by a recombinant plasmid and evaluate its antitumor effect on laryngeal squamous carcinoma in vitro and in vivo.MethodsA plasmid containing 3 different short hairpin RNA (shRNA) segments termed pEGFP‐shVEGF‐shTERT‐shBcl‐xl was constructed. Plasmids containing single shRNA against each target (VEFG, TERT, BCL‐xl alone) individually were also constructed as control. Cells were treated with these plasmids. The expression of targeted genes as well as apoptosis of tumor cells were evaluated after treatment with multiple shRNA vectors or control vectors. The mRNA and protein expression were determined by RT‐PCR and western blotting. Cell viability was examined using the MTT assay. Apoptotic morphological alterations were observed by Hoechst staining and electron microscopy. The in vivo antitumor effect was characterized in a nude mice model of laryngeal squamous carcinoma.ResultsWe demonstrated that a recombinant plasmid containing multiple shRNAs could effectively and simultaneously inhibit VEGF, TERT and Bcl‐xl mRNA and protein expression in the HEp‐2 cells; the plasmid containing the 3 different shRNAs exhibited a potent antitumor effect on LSCC both in vitro and in vivo, and could much more effectively induced cell apoptosis than each single shRNA. We also demonstrated that the simultaneous blockage of these 3 genes have a better inhibitory effect on human HEp‐2 cells than the blockage of each single shRNA.ConclusionOur study demonstrates that the application of vector‐based RNAi technology that involves hitting multiple targets will be a promising therapeutic modality in the gene therapy of human laryngeal cancers.SignificanceOur study provides experimental evidence for the clinical application of this technology in the future.SupportThis work was supported by the grants from the National Natural Science Foundation of China (No. 30471873, No.30672313 and No.30740012).
Atypical Pharyngitis In Suppurative Otitis Media Cases
Authors: Abou‐Bieh Alaa A , Salama Mona F 
Published: August 2008

ProblemUnexplained persistent or recurrent bacterial pharyngitis in some patients who suffer from infected middle ear cleft.MethodsBacteriological swabs were obtained from both the ears and the pharynx of 37 cases with chronic otorrhea and perforation, whom complain of recurrent or persistent sore‐throat. Then isolation and identification of the micro‐organisms were done. This included examination of direct Gram stained films and cultures. Isolated Gram negative bacilli were subjected to further identification by the biochemical reactions and antibiotyping. Identical isolates from the same patient (ear and pharyngeal swabs) were subjected to further identification by genotyping using the pulsed field gel electrophoresis technique.Results6 cases (16%) showed identity in phenotypes and genotypes for ear and pharyngeal samples from the same patient. All pharyngeal isolates were Gram negative organisms. 4 of them were Pseudomonas aeruginosa, 1 was Proteus sp., and 1 was Escherichia coli. All of these 3 species are not known to be among the primary organisms which may cause pharyngitis.ConclusionBacterial pharyngitis in patients with chronically infected middle ear cleft may be attributed to the same organism invaded the middle ear mucosa. Also this study highlights some organisms as a pharyngeal invaders although they are not among the previously documented causatives of bacterial pharyngitis. But the study do not confirm the method of spread of these organisms and whether this was directly via the eustachian tube.SignificanceThe study correlates the causative organism of the middle ear infection and that infected the pharyngeal mucosa utilizing the advanced bacteriological identification and genotyping techniques.
Cochlear Soft Tissue Imaging Using In‐Line Phase Contrast
Authors: Fishman Andrew J , Christoph Rau , Lixin Fan , Richter Claus‐Peter 
Published: August 2008

ProblemMost contemporary imaging methods require invasive specimen preparation and/or are time consuming, or lack sufficient spatial resolution.MethodsExperiments were made at the Advanced Photon Source (APS), Argonne National Laboratory. The APS is a synchrotron radiation source of the third generation, for which the particular characteristic is the highly coherent X‐ray radiation. X‐rays are generated with an undulator, inserted in a straight section of the storage ring. Images taken with hard X‐rays and the grating interferometer were compared with images from the same specimen acquired with light microscopy.ResultsThe results show that imaging of cochlear soft tissue structures is possible with hard X‐rays and a grating interferometer.ConclusionImaging of cochlear soft tissue structures is possible with hard X‐rays and a grating interferometer.SignificanceIt is important to examine cochlear morphology from many points of view, including comparative anatomy, cochlear developmental changes, malformation caused by genetic defects, changes related to diseases, sensory physiology, and cochlear modeling. Best imaging results were obtained from in situ experiments in the absence of tissue distortion. However, most contemporary imaging methods require invasive specimen preparation and/or are time consuming, or lack sufficient spatial resolution. A method that potentially overcomes these shortcomings is presented in this paper and it uses hard X‐rays and a grating interferometer. Furthermore, hard X‐rays would allow imaging cochlear soft tissue structures without opening the cochlea itself.SupportThe UNICAT facility at the Advanced Photon Source is supported by the U.S. DOE under Award No. DEFG02‐91ER45439, through the Frederick Seitz Materials Research Laboratory at the University of Illinois at Urbana‐Champaign, the ORNL (U.S. DOE contract DE‐AC.
Customized Electric Suppression of Tinnitus in CI Subjects
Authors: Fine Esther L , Qing Tang , Rothholtz Vanessa S , Lu Thomas , Djalilian Hamid R , Zeng Fan‐Gang 
Published: August 2008

ProblemTo determine the degree of tinnitus suppression in cochlear implant patients by systematically varying stimulation parameters as a function of rate, level, and electrode.MethodsFive cochlear implant subjects with ipsilateral or bilateral tinnitus were included. Implants were stimulated at a basal, middle, and apical electrode, at 100pps and 5000 pps, at perceived level quieter than the tinnitus and at the most comfortable loudness level. Patients reported stimulus and tinnitus perception on a ten‐point scale every 30 seconds during and after stimulus delivery.ResultsAll subjects reported near or complete suppression of tinnitus under one or more test conditions. Complete accommodation to the stimulus occurred often, thus during suppression patients perceived very little sound or total silence. Residual inhibition lasted up to twenty minutes. Two of the subjects noted suppression when low rate stimulation was delivered to an apical electrode. One patient responded only to high rate stimulation to an apical electrode. The remaining two patients reported suppression under multiple conditions. One subject had the most dramatic and consistent effects with low rate stimulation to a middle electrode; high rate stimulation caused rebound tinnitus of up to five minutes.ConclusionAll patients experienced tinnitus suppression with electrical stimulation. Low rate stimulation overall was more effective in our subject group, and in two cases was the only effective suppressor.SignificancePrevious studies utilized only high rates of stimulation, and treatment failures occurred. Electrical stimulation is an effective, reproducible, and well‐tolerated treatment for tinnitus but stimulus customization is required on an individual basis.
Middle Ear Packing: Comparison Between Merogel and Gelfoam
Authors: Lipan Michael Julian , Ibraham Alava , Angeli Simon I , Van De Water Thomas R 
Published: August 2008

ProblemGelfoam has been used for decades in otologic surgery to support grafts and prostheses despite causing fibrosis and adhesions. More biocompatible packing materials could avoid these complications. This study compares Gelfoam with an injectable esterified hyaluronic acid, Merogel, as middle ear packing material after mucosal trauma.MethodsA randomized, blinded, controlled study was performed in 17 juvenile guinea pigs. Middle ear surgery with mucosal trauma was performed and middle ears were packed with Merogel or Gelfoam; unpacked contralateral ears were used as controls. Auditory brainstem response (ABR) thresholds were measured in 4 frequencies pre‐operatively, and repeated at 1, 2, and 6 weeks postoperatively. Gross analysis measured inflammatory reaction in each group. Statistical analysis was performed using ANOVA followed by post‐hoc analysis for ABR thresholds and packing remaining at 6 weeks. Non‐prametric tests were used for presence of mucosal inflammation, effusion and tympanic membrane perforation.ResultsABR threshold changes from baseline were minor and comparable between the Merogel group and the control group. Threshold change was higher in the Gelfoam group. This difference was seen in each frequency tested at each time interval (all p<0.05). Gross analysis showed 1) Mucosal inflammation higher in the Gelfoam group (p<0.05), 2) Effusions were higher in the Gelfoam group but the difference was not significant (p=0.07), 3) Tympanic membrane perforation was equally rare between groups (p>0.05), 4) Unabsorbed packing was higher in the Gelfoam group (p<0.05); little Merogel was detectable at time of sacrifice.ConclusionMiddle ear healing after surgery occurred similarly in the control group and the Merogel group. In contrast, the Gelfoam group demonstrated greater perturbation of hearing and a greater inflammatory reaction.SignificanceThese results support Merogel as an alternative to Gelfoam in middle ear packing after otologic surgery.SupportResearch grant from Medtronic ENT.
The Measurement of 2D Curvature of In‐Vivo Human Ear Canal
Authors: Yu Jen‐Fang , Chung‐chieh Fan , Chen Chin‐Kuo 
Published: August 2008

ProblemTo non‐invasively measure the 2D curvature of human ear canal and produce the earmold by the non‐invasive 3D ear impression.MethodsThe images of external ear were scanned by high‐resolution computed tomography (HRCT). The resolution for each slice was 512⋉512 pixels. The pixel size was 0.188⋉0.188mm and the slice thickness was 0.625mm. The boundary between tympanic membrane and external auditory meatus was enhanced by image processing. Additionally, 3D model of ear canal was reconstructed by 2D images. The length and angle of first and second bends of canal were measured based on the 3D model. 2D curvature of first and second bends of canal was then computed by sine and cosine laws.ResultsThe volume of ear canal was 862.0 cubic mm. The angle and curvature of superior wall of first bend at axial view were 121.5 degrees and 0.0685; of inferior wall of first bend were 246 degrees and −0.1102; of superior wall of second bend were 227.8 degrees and −0.0332; of inferior wall of second bend were 143.1 degrees and 0.0130 respectively. 2D curvature of superior and inferior wall of first and second bends was diagrammed.ConclusionThe 2D curvature of ear canal at first and second bends could be measured and produce the ear impression non‐invasively. The geometry of canal changed by tumors is a common syndrome in ear disease. Therefore, the geometry of ear canal can be tracked after the otoplasty.SignificanceThe 3D geometry of canal can help physicians diagnose the syndrome of external canal before otoplasty. Moreover, the hearing aid earmold can be made by non‐invasive ear impression instead of invasive ear impression.
Volumetric Rendering of Human Inner Ear by MR Imaging
Authors: Yu Jen‐Fang , Chin Wei‐Chung , Wu Che‐Ming , Ng Shu‐Hang 
Published: August 2008

ProblemTo non‐invasively measure in‐vivo human inner ear by MRI and measure the geometry of vestibule by the reconstructed 3D model of inner ear for further diagnosis of large vestibular aqueduct syndrome (LVAS).Methods3‐T MR scanner, MAGNETOM Trio made by Siemens, was utilized. The TR/TE for MR imaging of 7 patients was 5.65/2.6 ms and the voxel size was 0.5 mm X 0.5 mm X 0.5 mm for single slice of 48 slices. The configuration of semicircular canals, vestibule and cochlea could be detected by threshold. The 3D geometry of inner ear was then computed based on the thickness of slice.ResultsThe surface area and volume of semicircular canals for 7 normal ears were 217.85 square mm and 63.56 cubic mm; of vestibule were 105.88 square mm and 56.36 cubic mm; of cochlea were 171.84 square mm and 81.29 cubic mm respectively. The variation of volumes of vestibule and cochlea could be quantified non‐invasively. The correlation between the volume and the level of LVAS will be analyzed once the number of volunteer reaches a statistically significant level.ConclusionThe variation for the geometry of vestibule could be measured non‐invasively. The grade of LVAS can be assessed by the obtained 3D model of semi‐circular canal, vestibule and cochlea.SignificanceAccording to the 3D model, the geometry of inner ear can be measured, and the syndrome can be revealed directly to help clinical diagnosis of LVAS more accurately.
Evaluation of the PEAK PlasmaBlade for ENT Surgery
Authors: Chang Kay W , Carlson Grace A , Eric Huang 
Published: August 2008

ProblemTraditional electrosurgical instruments are known to have an associated zone of thermal injury to the residual tissue. The compromised tissue left behind in the body may compromise wound healing and also may cause post operative pain. The PEAK PlasmaBlade is a new tissue dissection tool that uses pulsed radiofrequency energy to generate a highly focused plasma field at the tip of the device. This creates an effective cutting edge with simultaneous hemostasis while the blade remains near body temperature. A comparative study of tissue cutting and hemostasis was conducted to evaluate the characteristics of this technology.MethodsPorcine mucosal and lymphoid tissue was subjected to a series of surgical incisions using the PlasmaBlade, a scalpel, a traditional electrosurgery (bovie) blade style tip, and a Coblation EVac 70 wand. Both low and high settings were evaluated for PlasmaBlade, bovie, and Coblation. Blood loss following the cut was evaluated. Histology samples were harvested immediately after and evaluated for collateral tissue damage at the incision site. Thermal imaging of all the devices in an active cutting mode was also conducted.ResultsHistological evaluation of the tissue samples showed that the PlasmaBlade cuts produced minimal collateral damage compared to cuts made with the other electrosurgical instruments, which demonstrated greater thermal damage. Bleeding control (hemostasis) was equivalent for the Plasma‐Blade versus bovie and Coblation. Thermal imaging showed the PlasmaBlade operating in a range of 40 to 100 C which was similar to the Coblation operating temperatures. Traditional electrosurgery produced temperatures well in excess of 200 C.ConclusionThe PEAK PlasmaBlade is a promising new instrument which provides atraumatic, scalpel–like, cutting and bovie‐like hemostasis, resulting in minimal bleeding and tissue injury.SignificanceThere is great potential for this becoming an important tool for common ENT procedures such as tonsillectomy and adenoidectomy, specifically in reducing the pain and morbidity of recovery.
Fgf8 is Necessary for Normal Frontonasal Development
Authors: Wittkopf Maria , Goudy Steven L 
Published: August 2008

ProblemCraniofacial development is a complex process. We explore the role of ectodermal Fgf8 during craniofacial development in mice. Fgf8 is a multi‐functional growth factor known to induce cell migration and differentiation. We hypothesize that Fgf8 is necessary for frontonasal development. To determine its role, we selectively removed Fgf8 signaling in cells expressing the AP2 gene.MethodsWe generated AP2 Cre Fgf8 f/f R26R mice at e13–18. The embryos are harvested and fixed. They are dehydrated or saturated in 30% sucrose, then embedded in paraffin or OCT compound, respectively, for sectioning. The paraffin sections are used for morphologic examination following H&E and PAS staining. The cryosections are used for X‐gal staining and immunofluorescence. Skeletal preparations are used to assess the craniofacial skeleton.ResultsAP2 Cre mice are examined identifying AP2 expression in the developing epithelium. Gross examination of the AP2 Cre Fgf8 f/f mice reveals severe mid‐face shortening and micrognathia. These mice are nonviable due to their severe facial abnormalities. Close inspection reveals prominent eyes that appear normally formed but lack eyelids. The skeletal preparation of the AP2 Cre Fgf8 f/f mouse demonstrates almost absent mandibular development and hypoplastic maxilla. This correlates with the hypoplastic, ill‐organized sinus cavities with lack of nasal septum development seen on histologic sections. Examination of the epithelium and oral mucosa of these mutant mice demonstrates a verrucous morphology with poor differentiation.ConclusionFgf8 expression in the ectoderm appears to be necessary for frontonasal development in mice. Without epithelial Fgf8 expression, the craniofacial and epidermal development is severely affected. Future studies will further characterize the epithelial and mesenchymal phenotype of the AP2 Cre Fgf8 f/f mutant mice.SignificanceThe Fibroblast Growth Factor (Fgf) family is involved in multiple steps of craniofacial formation. Further studies elucidating the specific roles of its members, including Fgf8, will help better understand and manage craniofacial malformations.
Growth Factors in Infantile Hemangiomas
Authors: Tan‐Geller Melin , Min‐Jung O Teresa , Zaida Alipio , Fink Louis , Yongming Ma , Waner Milton 
Published: August 2008

ProblemInfantile hemangiomas have a well‐known distinct proliferative phase characterized by rapid proliferation of capillaries, followed by an involuting phase characterized by spontaneous and steady regression of the tumor. Histologically, proliferating hemangiomas are composed of masses of compact capillaries lined by plump endothelial cells with high mitotic rates. As the lesions involute, mitosis gradually decreases with increased apoptosis of endothelial cells, and vascular tissue is gradually replaced with fibrofatty tissue. Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) are among several markers that have been qualitatively found in proliferating and involuting phases of infantile hemangiomas, respectively. The purpose of this study is to quantitatively measure growth factors in proliferating and involuting hemangiomas.MethodsA high‐throughput xMAP multiplex immunobead assay technology (Luminex Corp., Austin, TX) was used to test VEGF, FGF, endothelial growth factor (EGF), and granulocyte‐colony stimulating factor (G‐CSF) in 22 infantile hemangioma specimens, 8 plasma specimens from hemangioma patients, and normal skin. Results were then correlated to histologic findings at the time of surgical removal.ResultsWhen compared to plasma and normal skin as controls, infantile hemangiomas demonstrated increased amounts of VEGF and EGF in actively proliferating hemangiomas and increased amounts of FGF, in both proliferating and involuting hemangiomas. G‐CSF was insignificant in hemangioma specimens.ConclusionVEGF, EGF and FGF are upregulated in infantile hemangiomas and may represent important therapeutic targets.SignificanceThis is the first study to quantitatively measure growth factors in infantile hemangiomas at different growth stages. Definitive evidence of increased growth factors in proliferating hemangiomas may lead to further consideration of angiogenic inhibitors as an alternative treatment modality to surgery, laser or steroids.SupportThis research study was supported by the Vascular Birthmarks Foundation.
The Leicester Olfactometer
Authors: Philpott Carl M , Goodenough Paul C , Allan Clark , Murty George E 
Published: August 2008

ProblemThe objective of this study was to develop a useful and cost‐effective olfactometer for routine clinical use. The apparatus was developed to provide a standardized threshold test for patients with olfactory disorders presenting in the ENT clinic.MethodsA prospective study of olfactory thresholds in 48 healthy volunteers on 2 consecutive occasions, undergoing quantitative testing with an olfactometer. Further studies of 10 subjects performing 20 tests and 100 subjects performing a single test were also performed. An olfactometer was designed to deliver a semi‐automated threshold test for an odor. It was designed as a device containing 8 logarithmic dilutions of an odor along with a control valve operated by software from a laptop computer. Common potential variables for olfactory threshold testing were considered including peak inspiratory flow rate and smoking status. The odors used for the studies were phenethyl alcohol (PEA) and eucalyptol. Subjects were asked to perform 2 tests within 1 month of each other and the mean threshold score for each test was calculated to help derive a test‐retest score.ResultsConsistent olfactory thresholds for PEA were achieved with a mean concentration of 10–4. Test‐retest reliability scores for the olfactometer were rx = 0.78 (95% CI 0.67 to 0.89). Common variables thought to affect olfactory testing including peak inspiratory flow rate and smoking were not found to have a significant effect on the threshold scores.ConclusionThe Leicester Olfactometer provides a simple and cost‐effective method of reliably assessing olfactory thresholds in the outpatient clinic.SignificanceRoutine testing of olfaction can be provided with a sophisticated yet user friendly format that overcomes the expense of single use test kits and other commercially available kits.SupportDepartmental research funds used.
R406 – Treatment of Squamous Cell Carcinoma of the Hypopharynx
Authors: Chedid Helma Maria , Lehn Carlos Neutzling 
Published: August 2008

ProblemSquamous cell carcinoma of the hypopharynx has been diagnosed at a late stage, including in developed countries, thus denoting worse prognosis. An association between surgery and radiotherapy is the standard treatment for advanced clinical stages. Our aim was to assess the clinical and treatment factors of tumors of the hypopharynx that were treated surgically and with postoperative radiotherapy.MethodsThis was a retrospective study on 174 patients, among whom two patients were in clinical stage (CS) I, four in CS II, 46 in CS III, and 122 in CS IV. Among these, 222 neck dissections were performed, of which 48 were bilateral. Statistic analysis: Kaplan‐Meier methods.ResultsThe mean follow‐up was 31 months, and histological examinations showed that two patients were pT1, 15 pT2, 100 pT3 and 57 pT4. With regard to lymph nodes, 25 patients were pN0 and 149 patients were pN+. The disease‐free survival in CS III was 75%, versus 28% in CS IV (p=0.001). The disease‐free survival was 35% and the overall survival was 28%.ConclusionSurgical treatment for tumors of the hypopharynx occurred in advanced CS, with disease‐free survival of 35%.SignificanceThe overall survival and disease free‐survival among patients with squamous cell carcinoma of the hypopharynx undergoing surgery.