A Comparative Study of an Anti-Thrombotic Small-Diameter Vascular Graft with Commercially Available e-PTFE Graft in a Porcine Carotid Model

BACKGROUND@#We have designed a reinforced drug-loaded vascular graft composed of polycaprolactone (PCL) and polydioxanone (PDO) via a combination of electrospinning/3D printing approaches. To evaluate its potential for clinical application, we compared the in vivo blood compatibility and performance of PCL/PDO ? 10%DY grafts doped with an antithrombotic drug (dipyridamole) with a commercial expanded polytetrafluoroethylene (e-PTFE) graft in a porcine model. @*METHODS@#A total of 10 pigs (weight: 25–35 kg) were used in this study. We made a new 5-mm graft with PCL/PDO composite nanofiber via the electrospinning technique. We simultaneously implanted a commercially available e-PTFE graft (n = 5) and our PCL/PDO ? 10%DY graft (n = 5) into the carotid arteries of the pigs. No anticoagulant/antiplatelet agent was administered during the follow-up period, and ultrasonography was performed weekly to confirm the patency of the two grafts in vivo. Four weeks later, we explanted and compared the performance of the two grafts by histological analysis and scanning electron microscopy (SEM). @*RESULTS@#No complications, such as sweating on the graft or significant bleeding from the needle hole site, were seen in the PCL/PDO ? 10%DY graft immediately after implantation. Serial ultrasonographic examination and immunohistochemical analysis demonstrated that PCL/PDO ? 10%DY grafts showed normal physiological blood flow and minimal lumen reduction, and pulsed synchronously with the native artery at 4 weeks after implantation. However, all e-PTFE grafts occluded within the study period. The luminal surface of the PCL/PDO ? 10%DY graft in the transitional zone was fully covered with endothelial cells as observed by SEM. @*CONCLUSION@#The PCL/PDO ? 10%DY graft was well tolerated, and no adverse tissue reaction was observed in porcine carotid models during the short-term follow-up. Colonization of the graft by host endothelial and smooth muscle cells coupled with substantial extracellular matrix production marked the regenerative capability. Thus, this material may be an ideal substitute for vascular reconstruction and bypass surgeries. Long-term observations will be necessary to determine the anti-thrombotic and remodeling potential of this device.

Fluoxetine Simultaneously Induces Both Apoptosis and Autophagy in Human Gastric Adenocarcinoma Cells

Fluoxetine is used widely as an antidepressant for the treatment of cancer-related depression, but has been reported to also have anti-cancer activity. In this study, we investigated the cytotoxicity of fluoxetine to human gastric adenocarcinoma cells; as shown by the MTT assay, fluoxetine induced cell death. Subsequently, cells were treated with 10 or 20 μM fluoxetine for 24 h and analyzed. Apoptosis was confirmed by the increased number of early apoptotic cells, shown by Annexin V-propidium iodide staining. Nuclear condensation was visualized by DAPI staining. A significant increase in the expression of cleaved PARP was observed by western blotting. The pan-caspase inhibitor Z-VAD-FMK was used to detect the extent of caspase-dependent cell death. The induction of autophagy was determined by the formation of acidic vesicular organelles (AVOs), which was visualized by acridine orange staining, and the increased expression of autophagy markers, such as LC3B, Beclin 1, and p62/SQSTM 1, observed by western blotting. The expression of upstream proteins, such as p-Akt and p-mTOR, were decreased. Autophagic degradation was evaluated by using bafilomycin, an inhibitor of late-stage autophagy. Bafilomycin did not significantly enhance LC3B expression induced by fluoxetine, which suggested autophagic degradation was impaired. In addition, the co-administration of the autophagy inhibitor 3-methyladenine and fluoxetine significantly increased fluoxetine-induced apoptosis, with decreased p-Akt and markedly increased death receptor 4 and 5 expression. Our results suggested that fluoxetine simultaneously induced both protective autophagy and apoptosis and that the inhibition of autophagy enhanced fluoxetine-induced apoptosis through increased death receptor expression.

Suspicious T1 colon cancer with synchronous liver metastasis not detected by preoperative imaging study

Colorectal carcinoma invading the submucosa but not the muscularis propria (pT1) represents the earliest form of clinically relevant colorectal cancer in most patients. T1 colorectal cancer with synchronous liver metastasis is considered to be rare. We report a rare case of T1 colon cancer with synchronous liver metastasis not detected by preoperative imaging study. A 54-year-old male patient presented to our department for treatment of sigmoid colon cancer following an endoscopic submucosal dissection. Histopathological examination revealed the pedunculated mass was moderately differentiated adenocarcinoma without lymphovascular invasion and the depth of submucosal invasion was 2,000 µm, the resection margin was not involved. We performed a laparoscopic anterior resection with lymph node dissection. After the 3 months, the patient's carcinoembryonic antigen level elevated from 1.4 to 7.26 ng/mL (normal level: <1.5 ng/mL) and the abdominal computed tomography and FDG-PET/CT (positron emission tomography-computed tomography) showed multiple hepatic metastases in both hepatic lobes (SUVmax: 5.6) without evidence of local recurrence or lymphadenopathy. We strongly suspected a synchronous liver metastasis not detected by imaging study as opposed to a systemic recurrence. Therefore, evaluation and follow-up protocol of T1 colorectal cancer should be changed for discovery and prediction of synchronous liver metastasis; because we cannot exclude the possibility of synchronous liver metastasis.

Managing the behavior of a patient with autism by sedation via submucosal route during dental treatment

In sedation via the submucosal route, the drug is administered through the maxillary buccal submucosa. It is time saving, effective, and safe. Patients with autism, a mental disorder, often find it hard to make relationships with other people. These patients display a strong resistance to dental treatment and sedation. This study reports a successful case of behavioral management during dental treatment, using sedation via the submucosal route. The patient was strongly resistant to sedation via the oral, intramuscular, and intravenous routes. The drug used was 9 mg (0.1 mg/kg) of midazolam. Through this case report, we reaffirm the significance of sedation via the submucosal route, and expect that it will be used more frequently for patients with autism, who display behaviors that are difficult to manage, patients with other disabilities, and children.

GEE: An Informatics Tool for Gene Expression Data Explore / 대한의료정보학회지

OBJECTIVES: Major public high-throughput functional genomic data repositories, including the Gene Expression Omnibus (GEO) and ArrayExpress have rapidly expanded. As a result, a large number of diverse high-throughput functional genomic data retrieval systems have been developed. However, high-throughput functional genomic data retrieval remains challenging. METHODS: We developed Gene Expression data Explore (GEE), the first powerful, flexible web and mobile search application for searching whole-genome epigenetic data and microarray data in public databases, such as GEO and ArrayExpress. RESULTS: GEE provides an elaborate, convenient interface of query generation competences not available via various high-throughput functional genomic data retrieval systems, including GEO, ArrayExpress, and Atlas. In particular, GEE provides a suitable query generator using eVOC, the Experimental Factor Ontology (EFO), which is well represented with a variety of high-throughput functional genomic data experimental conditions. In addition, GEE provides an experimental design query constructor (EDQC), which provides elaborate retrieval filter conditions when the user designs real experiments. CONCLUSIONS: The web version of GEE is available at http://www.snubi.org/software/gee, and its app version is available from the Apple App Store.

Influence of old age on the postoperative outcomes of obstructive colorectal cancer surgery after the insertion of a stent

PURPOSE: In some patients more than 70 years of age with obstructive colorectal cancer, their concerns about the postoperative complications lead them to refuse surgery after the insertion of a stent. This study aimed to compare the postoperative outcomes between obstructive colorectal cancer patients aged less than 70 years and those aged 70 years and more who underwent surgery after the insertion of a colonoscopic stent. METHODS: Patients with obstructive colorectal cancer who underwent surgery after the insertion of a colonoscopic stent between March 2004 and March 2014 were reviewed retrospectively by using medical records. The patients were divided into two groups: 22 patients were aged less than 70 years (group A) and 30 patients were aged more than 70 years (group B). RESULTS: Although no significant difference in comorbidity was noted between the two groups, the American Society of Anesthesiologists (ASA) score was higher in group B. There was no significant difference in cancer location, stage, or the time from the insertion of the stent to operation. The perioperative results including operation time, blood loss, and length of stay were not significantly different between the groups. The postoperative complications were also not significantly different. CONCLUSION: The surgical outcomes of elderly patients were similar to those of younger patients, despite higher ASA scores. These results indicate that surgery can be performed safely in elderly patients with obstructive colorectal cancer after the insertion of a stent.

The Effect of Memantine on Experimentally Gentamicin Induced Vestibulotoxicity in Guinea Pigs / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: In general, aminoglycosides are known to cause ototoxicity through the glutamate induced nitric oxide production. The N-methyl-D-aspartate (NMDA) related glutamate receptors have a pivotal role in aminoglycoside induced ototoxicity. Memantine is known as a safe NMDA antagonist and is also used in some neurologic insults, such as the Alzheimer disease. In this study, we observed the effect of memantine on gentamicin induced vestibulotoxicity in an animal model. MATERIALS AND METHOD: Vestibulotoxicity was induced with intratympanic administration of gentamicin and memantine was injected intraperitoneally to a study group. Histomorphological studies for vestibule were performed via light and electron microscopy. Immunohistochemical studies were performed for iNOS, nitrotyrosine and apoptosis via TUNEL staining. RESULTS: The numbers of hair cells were decreased significantly in the gentamicin group than in the gentamicin-memantine group. Increased immunoreactivities for iNOS and nitrotyrosine were observed in the gentamicin group than in the memantine-pretreated gentamicin group. TUNEL positive cells were more frequently observed in the gentamicin group than in the memantinepretreated gentamicin group. CONCLUSION: This result shows that memantine has a protection effect on gentamicin-induced vestibulotoxicity in an animal model.

Hip Joint Surgery without Transfusion in Patients Who Were Jehovah's Witnesses: A Report of Two Cases

Jehovah's Witnesses are widely known for their prohibition for accepting blood transfusion. Because of the firm refusal to receive transfused blood and blood components by Jehovah's Witnesses, the management of Jehovah's Witness patients with severe bleeding is often complicated by medical, ethical and legal concerns. We report here on two cases of successful treatment of Jehovah's Witnesses who underwent total hip replacement for secondary osteoarthritis and Chiari osteotomy for acetabular dysplasia.

Robotic Total Knee Arthroplasty: Minimal Follow-up of 3 Years

PURPOSE: We wanted to evaluate the clinical and radiographic results of robotic-assisted implantation of TKAs with a minimum follow-up of three years. MATERIALS AND METHODS: 50 TKAs using ROBODOC(R) (Integrated Surgical Systems, Sacramento, CA, USA) were included in this study. We assessed the radiographic measurements with regard to the change of the mechanical axis and the inclination of the femoral and tibial components. The clinical results were evaluated with using the range of motion (ROM), the Hospital for Special Surgery (HSS) scores and the Western Ontario and McMaster University (WOMAC) scores. RESULTS: The angle formed by the mechanical axis of the femur and tibia was corrected from 6.57degrees varus to 0.49degrees valgus. The mean coronal inclination of the femoral and tibial components was 89.52degrees and 90.12degrees, respectively, and the mean sagittal inclination of the femoral and tibial components was 1.06degrees and 85.56degrees, respectively. There were 45 excellent and 5 acceptable results for the femoral component, and 38 excellent and 11 acceptable results for the tibial components. On the clinical assessment, the ROM improved from 124.9degrees to 128.4degrees, and the improvements of the HSS and WOMAC scores were 70.06 to 95.72 and 65.64 to 28.92, respectively. CONCLUSION: A surgical robot system that has the ability to execute highly precise preoperative planning and intraoperative procedure for TKA provides good clinical and radiographic results at three years follow-up.

Evaluation of a competitive ELISA for antibody detection against avian influenza virus

Active serologic surveillance is necessary to control the spread of the avian influenza virus (AIV). In this study, we evaluated a commercially-available cELISA in terms of its ability to detect AIV antibodies in the sera of 3,358 animals from twelve species. cELISA detected antibodies against reference H1- through H15-subtype AIV strains without cross reactivity. Furthermore, the cELISA was able to detect antibodies produced following a challenge of the AIV H9N2 subtype in chickens, or following vaccination of the AIV H9 or H5 subtypes in chickens, ducks and geese. Next, we tested the sensitivity and specificity of the cELISA with sera from twelve different animal species, and compared these results with those obtained by the hemagglutination-inhibition (HI) test, the "gold standard" in AIV sera surveillance, a second commercially-available cELISA (IZS ELISA), or the agar gel precipitation (AGP) test. Compared with the HI test, the sensitivities and specificities of cELISA were 95% and 96% in chicken, 86% and 88% in duck, 97% and 100% in turkey, 100% and 87% in goose, and 91% and 97% in swine, respectively. The sensitivities and specificities of the cELISA in this study were higher than those of IZS ELISA for the duck, turkey, goose, and grey partridge sera samples. The results of AGP test against duck and turkey sera also showed significant correlation with the results of cELISA (R-value >0.9). In terms of flock sensitivity, the cELISA correlated better with the HI test than with commercially-available indirect ELISAs, with 100% flock sensitivity.

Effects of Nasal Instillation of Staphylococcal Enterotoxin B on Allergic Inflammation in Mice / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The role of Staphylococcus aureus enterotoxin B (SEB) in allergic rhinitis remains controversial. We used a mouse model of airway allergy to determine the effects of nasal instillation of SEB on allergic inflammation. MATERIALS AND METHOD: BALB/c mice were intranasally sensitized with compound of Aspergillus melleus proteinase (AMp) and ovalbumin (ova) in the presence (group 3) or absence of SEB (group 2). Control mice were intranasally sensitized with either phosphate buffered saline (PBS)(group 1) or SEB (group 4) alone. The production of serum antigen-specific antibodies and total IgE, and concentrations of cytokines including interleukin-4 (IL-4), IL-5, interferon-gamma (IFN-gamma) in nasal lavage fluid (NLF) and broncoalveolar lavage fluid (BALF) were compared among the groups. Pathologic studies for eosinophilic infiltrations in the nasal mucosa and peribronchial area were also conducted. RESULTS: Serum ova-specific immunoglobulin E (IgE) & immunoglobulin G1 (IgG1) were significantly increased in group 2 and 3 compared to group 1. The concentrations of IL-4 in BALF were significantly increased in group 2, 3, and 4 compared to group 1. The concentrations of IL-5 in BALF and NLF were significantly increased in Group 2, 3, and 4 compared to group 1. The concentrations of IFN-gamma were significantly increased in group 3 and 4 compared to group 2 although there was no significant difference among the groups in NLF. Group 2 demonstrates increased infiltration of eosinophils in the nasal mucosa and peribronchial area compared to group 3 and 4. CONCLUSION: These results suggest that the nasal exposure to SEB did not aggravate inflammation in allergic mice.

In Vivo Comparison of Isometricity between Navigational and Conventional Technique in an ACL Reconstruction / 대한정형외과학회잡지

PURPOSE: To compare isometricity between the navigational and conventional technique during an anterior cruciate ligament (ACL) reconstruction before fixating the graft. MATERIALS AND METHODS: Twenty-three patients with an ACL insufficiency were enrolled in this study. After finishing the tibial tunnel preparation using a navigational technique, a femoral tunnel site was marked using either the navigational (Orthopilot(R)) or conventional (Arthrex(R) 5 mm off-set guide) technique. After passing the suture material attached to the guide pin through each femoral site, isometric tests were then performed using a specially designed device during full range of motion of the knee. RESULTS: An mean isometricity after the navigational and the conventional technique was 3.0 mm and 4.6 mm respectively. The isometricity after the navigational technique was significantly better than that after the conventional technique (p=0.000). The navigational isometric point was usually 0 to 5 mm anterior or antero-lateral to that at the point of the conventional technique. The mean distance between the tunnels by two techniques was 1.35 mm. There was a strong positive correlation between the difference in isometicity and the positional relationship of the femoral tunnel (r2=0.778, p=0.000). CONCLUSION: An ACL reconstruction using the navigational technique provides better isometricity than that obtained using the conventional technique.

A Case of Miller-Dieker Syndrome with Infantile Spasm and Lennox-Gastaut Syndrome / 대한소아신경학회지

Miller-Dieker syndrome is a contiguous gene deletion syndrome involving chromosome 17p13.3, which is characterized by type 1(classical) lissencephaly and typical craniofacial abnormalities. Children with Miller-Dieker syndrome have profound psychomotor retardation, seizures that often are intractable, chronic feeding problems that lead to recurrent pneumonia, and shortened lifespan. We have experienced a Miller-Dieker syndrome female who has lived to 8years, showing severe mental and motor retardation and intractable epilepsy. She was diagnosed as Miller-Dieker syndrome in the neonatal period, showing typical facial features, type 1 lissencephaly, and chromosome 17p13.3 microdeletion in fluorescence in situ hybridization. Infantile spasm occurred at 4 months of age and progressed to Lennox-Gastaut syndrome at 3 years and 6 months, both of which were not controlled by antiepileptic drugs.

A Case of Orgasmic Aura Associated with Temporal Lobe Epilepsy from the Nondominant Hemisphere

We experienced a patient with an orgasmic aura originating from the right mesial temporal structure. A 36-year-old right-handed woman suffered from a specific sensation of sexual arousal and orgasm-like euphoria lasting 1~2 minutes for several years. Video EEG monitoring ascertained those sensations as epileptic in nature arising from the right mesial temporal area through a foramen ovale electrode. The findings of 99mTc-ECD-SPECT and 18F-FDG PET were concordant with those of the brain MRI which was pathologically consistent with hippocampal sclerosis.

Development of a Knowledge Base for Korean Pharmacogenomics Research Network

Pharmacogenomics research requires an intelligent integration of large-scale genomic and clinical data with public and private knowledge resources. We developed a web-based knowledge base for KPRN (Korea Pharmacogenomics Research Network, http://kprn.snubi. org/). Four major types of information is integrated; genetic variation, drug information, disease information, and literature annotation. Eighteen Korean pharmacogenomics research groups in collaboration have submitted 859 genotype data sets for 91 disease-related genes. Integrative analysis and visualization of the large collection of data supported by integrated biomedical pathways and ontology resources are provided with a user-friendly interface and visualization engine empowered by Generic Genome Browser.

Rapid prenatal diagnosis for chromosomal aneuploidy using cDNA microarray-based comparative genomic hybridization / 대한산부인과학회지

OBJECTIVE: Prenatal cytogenetic diagnosis is limited to metaphase karyotype analysis of cultured cells obtained by amniocentesis or chorionic villus sampling. Moreover, genome wide analysis cannot be performed by FISH analysis using specific probe. Array comparative genomic hybridization (CGH) offers a number of advantages over conventional cytogenetic analysis and FISH. Microarray CGH can be highly comprehensive, amenable to very high resolution, sensitive and fast. The objective of this study was to determine the clinical use of cDNA microarray CGH for detection of fetal aneuploidy. METHODS: 21 amniotic fluid samples and 6 chorionic villi samples were obtained from 27 pregnant women in 9-19 gestational weeks. Genomic DNA was extracted from each sample and amplified. For cDNA microarray CGH analysis, test DNA sample and reference DNA sample were labeled with Cy3-dUTP and Cy5-dUTP, respectively. Each sample of labeled test and reference DNA was hybridized to microarray. The result was analysed with axon scanner and compared with cytogenetic analysis and FISH. RESULTS: In 27 cases, 3 cases with trisomy 21 and 1 case with trisomy 18 had increased hybridization signals on chromosome 21 and chromosome 18. One case with 45,X had decreased signals on chromosome X. One case with 46,X,i(Xq) had decreased signal on short arm of chromosome X and increased signal on long arm. And one case with 47,XYY had two fold increased signal on Y chromosome. cDNA microarray based CGH correctly identified fetal aneuploidy in all of the 7 cases with aneuploid fetuses. CONCLUSION: Prenatal genetic diagnosis by cDNA microarray-based CGH is an useful, innovative, rapid and accurate method. It is promising technique allowing rapid screening for whole chromosomal changes including aneuploidy, and may augment standard karyotyping techniques for prenatal genetic diagnosis by providing additional molecular information. This method may aid the discovery and description of minor genetic aberration, potentially enhancing future prenatal genetic diagnostic application.

A Case of Primary Small Cell Carcinoma of the Larynx / 대한이비인후과학회지

Small cell carcinoma mainly occurs in the lung and extrapulmonary primary small cell carcinoma is uncommon. In the head and neck region, small cell carcinoma most commonly arises in the larynx and has been reported in the nasal cavity, paranasal sinuses, tongue, salivary glands, esophagus, and trachea. We have recently experienced a case of primary small cell carcinoma of the supraglottis in a 69-year-old male. The patient was treated by sequential chemoradiotherapy. We reported this case with a review of the literature.

Xperanto: A Web-Based Integrated System for DNA Microarray Data Management and Analysis

DNA microarray is a high-throughput biomedical technology that monitors gene expression for thousands of genes in parallel. The abundance and complexity of the gene expression data have given rise to a requirement for their systematic management and analysis to support many laboratories performing microarray research. On these demands, we developed Xperanto for integrated data management and analysis using user-friendly web-based interface. Xperanto provides an integrated environment for management and analysis by linking the computational tools and rich sources of biological annotation. With the growing needs of data sharing, it is designed to be compliant to MGED (Microarray Gene Expression Data) standards for microarray data annotation and exchange. Xperanto enables a fast and efficient management of vast amounts of data, and serves as a communication channel among multiple researchers within an emerging interdisciplinary field.

Imaging Evidence of Basal Ganglia Pathology in Hemi choreoballistic Movement of the Patient with Nonketotic Hyperglycemia: Case Report with Serial Follow Up of Neuroimages

The mechanism of chorea underlying nonketotic hyperglycemia was controversial. Serial follow up of brain MRI, 99mTc-ECD SPECT, and 18F-FDG PET in conjunction with clinical observation was done to clarify the pathologic localization. From the functional neuroimages, according to the clinical improvement, the relevant pathology was localized on the lentiform nucleus, mainly on the putamen. In caudate, the mismatch between glucose metabolism and blood flow was observed during and after choreoballistic movement which suggested an important cue to understand the pathogenesis of chorea.

Anatomic Changes of Intranasal and Surrounding Bony Structures in Patients with Nasal Septal Deviation: A CT Analysis / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: In the cases of nasal septal deviation (NSD), bilateral nasal structures, such as inferior turbinate, nasal floor, or lateral nasal wall, are often asymmetric. These patterns may be somewhat uniform according to the direction of septal deviation. The aims of this study are to establish the anatomical patterns of the intranasal and surrounding bony structures in the cases of NSD by using radiologic measurement. SUBJECTS AND METHOD: We took OMU CT scans of 38 adult non-traumatic NSD patients without concurrent sinonasal inflammation. For each patient, we selected 4 consecutive coronal images of the most severely deviated portion for the measurement. We set various parameters which could reflect the anatomic patterns of the bony structures, then measured them in the selected images. RESULTS: The levels of bilateral nasal floors were not the same, and the floor of nasal cavity was significantly declined to convex side. The angle of lateral nasal wall was significantly larger in the concave side than in the convex side. The horizontal width or the angle of the inferior turbinate was significantly larger in the concave side than in the convex side. CONCLUSION: In the cases of NSD, the symmetry of bilateral intranasal or surrounding bony structures was altered significantly, and its pattern was uniform according to the direction of deviation. These findings suggest that non-traumatic NSD may be the result of asymmetric growth of facial bones.