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1.  Voltage Regulation of Connexin Channel Conductance 
Yonsei Medical Journal  2014;56(1):1-15.
Voltage is an important parameter that regulates the conductance of both intercellular and plasma membrane channels (undocked hemichannels) formed by the 21 members of the mammalian connexin gene family. Connexin channels display two forms of voltage-dependence, rectification of ionic currents and voltage-dependent gating. Ionic rectification results either from asymmetries in the distribution of fixed charges due to heterotypic pairing of different hemichannels, or by channel block, arising from differences in the concentrations of divalent cations on opposite sides of the junctional plaque. This rectification likely underpins the electrical rectification observed in some electrical synapses. Both intercellular and undocked hemichannels also display two distinct forms of voltage-dependent gating, termed Vj (fast)-gating and loop (slow)-gating. This review summarizes our current understanding of the molecular determinants and mechanisms underlying these conformational changes derived from experimental, molecular-genetic, structural, and computational approaches.
doi:10.3349/ymj.2015.56.1.1
PMCID: PMC4276742  PMID: 25510741
Connexin; voltage dependence; rectification; gating
2.  Efficacy of Surgical Treatment for Brain Metastasis in Patients with Non-Small Cell Lung Cancer 
Yonsei Medical Journal  2014;56(1):103-111.
Purpose
Patients with non-small cell lung cancer (NSCLC) and simultaneously having brain metastases at the initial diagnosis, presenting symptoms related brain metastasis, survived shorter duration and showed poor quality of life. We analyzed our experiences on surgical treatment of brain metastasis in patients with NSCLC.
Materials and Methods
We performed a single-center, retrospective review of 36 patients with NSCLC and synchronous brain metastases between April 2006 and December 2011. Patients were categorized according to the presence of neurological symptoms and having a brain surgery. As a result, 14 patients did not show neurological symptoms and 22 patients presented neurological symptoms. Symptomatic 22 patients were divided into two groups according to undergoing brain surgery (neurosurgery group; n=11, non-neurosurgery group; n=11). We analyzed overall surgery (OS), intracranial progression-free survival (PFS), and quality of life.
Results
Survival analysis showed there was no difference between patients with neurosurgery (OS, 12.1 months) and non-neurosurgery (OS, 10.2 months; p=0.550). Likewise for intracranial PFS, there was no significant difference between patients with neurosurgery (PFS, 6.3 months) and non-neurosurgery (PFS, 5.3 months; p=0.666). Reliable neurological one month follow up by the Medical Research Council neurological function evaluation scale were performed in symptomatic 22 patients. The scale improved in eight (73%) patients in the neurosurgery group, but only in three (27%) patients in the non-neurosurgery group (p=0.0495).
Conclusion
Patients with NSCLC and synchronous brain metastases, presenting neurological symptoms showed no survival benefit from neurosurgical resection, although quality of life was improved due to early control of neurological symptoms.
doi:10.3349/ymj.2015.56.1.103
PMCID: PMC4276743  PMID: 25510753
Non-small cell lung cancer; brain metastasis; neurosurgery; quality of life; treatment outcome
3.  The Effect of Bortezomib on Expression of Inflammatory Cytokines and Survival in a Murine Sepsis Model Induced by Cecal Ligation and Puncture 
Yonsei Medical Journal  2014;56(1):112-123.
Purpose
Although the proteasome inhibitor known as bortezomib can modulate the inflammatory process through the nuclear factor-kappa B signaling pathway, the immunomodulatory effect of pre-incubated bortezomib has not been fully evaluated for inflammation by infectious agents. Therefore, we evaluated the effect of bortezomib on the expression of inflammatory cytokines and mediators in macrophage cell lines and on survival in a murine peritonitis sepsis model.
Materials and Methods
Bortezomib was applied 1 hr before lipopolysaccharide (LPS) stimulation in RAW 264.7 cells. The cecal ligation and puncture (CLP) experiments were performed in C57BL/6J mice.
Results
Pre-incubation with bortezomib (25 nM or 50 nM) prior to LPS (50 ng/mL or 100 ng/mL) stimulation significantly recovered the number of viable RAW 264.7 cells compared to those samples without pre-incubation. Bortezomib decreased various inflammatory cytokines as well as nitric oxide production in LPS-stimulated cells. The 7-day survival rate in mice that had received bortezomib at 0.01 mg/kg concentration 1 hr prior to CLP was significantly higher than in the mice that had only received a normal saline solution of 1 mL 1 hr prior to CLP. In addition, the administration of bortezomib at 0.01 mg/kg concentration 1 hr before CLP resulted in a significant decrease in inflammation of the lung parenchyma. Collectively, pretreatment with bortezomib showed an increase in the survival rate and changes in the levels of inflammatory mediators.
Conclusion
These results support the possibility of pretreatment with bortezomib as a new therapeutic target for the treatment of overwhelming inflammation, which is a characteristic of severe sepsis.
doi:10.3349/ymj.2015.56.1.112
PMCID: PMC4276744  PMID: 25510754
Bortezomib; proteasome inhibitor; lipopolysaccharide; inflammatory cytokines; cecal ligation and puncture
4.  Risk Factors for Osteoarthritis and Contributing Factors to Current Arthritic Pain in South Korean Older Adults 
Yonsei Medical Journal  2014;56(1):124-131.
Purpose
Although previous studies have focused on risk factors for osteoarthritis, there is some debate on this issue. Furthermore, associated factors with arthritic symptom (arthralgia) have not been sufficiently investigated, despite its clinical importance in the management of osteoarthritis. This study was performed to examine the risk factors for osteoarthritis and the contributing factors to current arthritic pain in older adults.
Materials and Methods
The Fourth Korean National Health and Nutrition Examination Surveys was conducted in 2009. Therein, 720 males and 1008 females aged 65 years and older were included. Comprehensive data on habitual, socioeconomic, medical, nutritional, and psychological factors were collected along with the presence of osteoarthritis and arthritic pain. After univariate analysis, binary logistic regression analysis was performed to identify risk factors for osteoarthritis and contributing factors to current arthritic pain.
Results
Age (p=0.005), female gender (p<0.001), higher body mass index (BMI) (p<0.001), and osteoporosis (p<0.001) were significant risk factors for osteoarthritis, while higher education level (p=0.025) was a protective factor for osteoarthritis. Higher BMI (p=0.047), lack of weekly moderate intensity activity (p<0.001), and unfavorable subjective health status (p<0.001) were significant factors contributing to current arthritic pain among subjects with osteoarthritis. Both osteoarthritis and current arthritic pain adversely affected health related quality of life.
Conclusion
Higher BMI, lack of weekly moderate intensity activity, and unfavorable subjective health status were significant factors contributing to current arthritic pain. More attention needs to be paid to psychiatric effects on osteoarthritis and joint related pain.
doi:10.3349/ymj.2015.56.1.124
PMCID: PMC4276745  PMID: 25510755
Osteoarthritis; joint related pain; risk factors; older adults
5.  Characteristics and Trends of Published Adult Hip Research over the Last Decade 
Yonsei Medical Journal  2014;56(1):132-138.
Purpose
We designed this study to demonstrate recent trends in the proportion of adult hip research in orthopedics, to identify countries leading the adult hip research, and to evaluate the relationship between the economic power of the countries and their contributions.
Materials and Methods
Studies published in seven select orthopedic journals were retrieved from PubMed. Among them, we determined the number of adult hip studies. The countries-of-origin of adult hip studies, and the economic power of the countries were investigated.
Results
A total of 7218 orthopedic publications and 1993 (27.6%) addressed adult hip research were identified. Adult hip studies increased from 313 (23.7%) in 2000 to 555 (27.9%) in 2011. Twenty-five countries accounted for 97.6% of the total number of adult hip studies, and gross domestic product correlated with publication volume (Spearman's rho, 0.723; p=0.000).
Conclusion
Researchers from a limited number of developed countries have published their studies in the adult hip discipline.
doi:10.3349/ymj.2015.56.1.132
PMCID: PMC4276746  PMID: 25510756
Hip; research; publishing; trends; PubMed
6.  Incidence of Deep Vein Thrombosis after Major Lower Limb Orthopedic Surgery: Analysis of a Nationwide Claim Registry 
Yonsei Medical Journal  2014;56(1):139-145.
Purpose
We aimed to evaluate the nationwide incidence and risk factors for symptomatic deep vein thrombosis (DVT) after major lower limb orthopedic surgeries.
Materials and Methods
The Korean Health Insurance Review and Assessment Service database was used to retrospectively identify International Classification of Disease-10 codes for DVT and operation codes representing hip arthroplasty, knee arthroplasty, and hip fracture surgeries. The age- and gender-adjusted annual incidence of DVT, rates of major lower limb orthopedic surgeries, and the postoperative incidence of DVT according to the surgical procedure were assessed.
Results
The age- and gender-adjusted annual incidence of DVT was 70.67 per 100000 persons/year. Compared to patients aged <49 years, the relative risk of DVT was five times higher in patients aged 50-69 and 10 times higher in patients aged >70 years (p<0.001). Females showed a greater relative risk for DVT than males (1.08; p<0.001). The incidence of postoperative DVT, according to the type of surgery, was significantly greater for knee replacement arthroplasty than for other forms of surgery (p<0.002). The relative risk of postoperative DVT was higher in females in knee replacement arthroplasty (1.47) and hip fracture surgery (2.25) groups, although relatively lower in those who underwent hip replacement arthroplasty (0.97).
Conclusion
Among major lower limb surgeries, advanced age, female gender, and undergoing a knee replacement arthroplasty were found to be risk factors for developing postoperative DVT. These findings further emphasize the need for orthopedic surgeons to consider the development of DVT after surgery in high-risk patients.
doi:10.3349/ymj.2015.56.1.139
PMCID: PMC4276747  PMID: 25510757
Deep vein thrombosis; incidence; hip arthroplasty; knee arthroplasty; hip fracture surgery
7.  Finite Element Analysis for Comparison of Spinous Process Osteotomies Technique with Conventional Laminectomy as Lumbar Decompression Procedure 
Yonsei Medical Journal  2014;56(1):146-153.
Purpose
The purpose of this study was to evaluate and compare the biomechanical behavior of the lumbar spine after posterior decompression with the spinous process osteotomy (SPiO) technique or the conventional laminectomy (CL) technique using a finite element (FE) model.
Materials and Methods
Three validated lumbar FE models (L2-5) which represented intact spine and two decompression models using SPiO and CL techniques at the L3-4 segment were developed. In each model, the ranges of motion, the maximal von Mises stress of the annulus fibrosus, and the intradiscal pressures at the index segment (L3-4) and adjacent segments (L2-3 and L4-5) under 7.5 Nm moments were analyzed. Facet contact forces were also compared among three models under the extension and torsion moments.
Results
Compared to the intact model, the CL and SPiO models had increased range of motion and annulus stress at both the index segment (L3-4) and the adjacent segments under flexion and torsion. However, the SPiO model demonstrated a reduced range of motion and annulus stress than the CL model. Both CL and SPiO models had an increase of facet contact force at the L3-4 segment under the torsion moment compared to that of the intact model. Under the extension moment, however, three models demonstrated a similar facet contact force even at the L3-4 model.
Conclusion
Both decompression methods lead to postoperative segmental instability compared to the intact model. However, SPiO technique leads to better segmental stability compared to the CL technique.
doi:10.3349/ymj.2015.56.1.146
PMCID: PMC4276748  PMID: 25510758
Lumbar spinal stenosis; spinous process osteotomies; conventional laminectomy; finite element model
8.  Effect of the Starting Point of Half-Pin Insertion on the Insertional Torque of the Pin at the Tibia 
Yonsei Medical Journal  2014;56(1):154-159.
Purpose
The authors have observed a failure to achieve secure fixation in elderly patients when inserting a half-pin at the anteromedial surface of the tibia. The purpose of this study was to compare two methods for inserting a half-pin at tibia diaphysis in elderly patients.
Materials and Methods
Twenty cadaveric tibias were divided into Group C or V. A half-pin was inserted into the tibias of Group C via the conventional method, from the anteromedial surface to the interosseous border of the tibia diaphysis, and into the tibias of Group V via the vertical method, from the anterior border to the posterior surface at the same level. The maximum insertion torque was measured during the bicortical insertion with a torque driver. The thickness of the cortex was measured by micro-computed tomography. The relationship between the thickness of the cortex engaged and the insertion torque was investigated.
Results
The maximum insertion torque and the thickness of the cortex were significantly higher in Group V than Group C. Both groups exhibited a statistically significant linear correlation between torque and thickness by Spearman's rank correlation analysis.
Conclusion
Half-pins inserted by the vertical method achieved purchase of more cortex than those inserted by the conventional method. Considering that cortical thickness and insertion torque in Group V were significantly greater than those in Group C, we suggest that the vertical method of half-pin insertion may be an alternative to the conventional method in elderly patients.
doi:10.3349/ymj.2015.56.1.154
PMCID: PMC4276749  PMID: 25510759
Fracture; tibia; diaphysis; external fixation
9.  Feasibility of Translaminar Screw Placement in Korean Population: Morphometric Analysis of Cervical Spine 
Yonsei Medical Journal  2014;56(1):159-166.
Purpose
To analyze the feasibility of unilateral and bilateral translaminar screw placement in Koran population, and compare the acceptance rate using previously reported data in American population.
Materials and Methods
The translaminar lengths, thickness, heights, and sagittal-diagonal measurements were performed. The feasibility analysis was performed using unilateral and bilateral 3.5 mm cervical screw placement on the CT scans within 0.5 mm of safety margin. We also performed radiographic analysis of the morphometric dimensions and the feasibility of unilateral and bilateral translaminar screw placement at C3-C7.
Results
Korean population had similar or significantly shorter translaminar lengths and thickness (lengths and thickness in C7 among males; lengths in C6-C7 and thickness in C4 among females) than American population, but had similar or significantly longer translaminar heights and sagittal-diagonal measurements (heights in C3-C7 and sagittal-diagonal measurements in C3-C6 among males; heights in C7 and sagittal-diagonal measurements in C3-C7 among females). Unilaterally, translaminar screw acceptance rates in C3-C7 were similar between Korean and American male population, but the rates in C4-C6 were significantly smaller between Korean and American female population. Bilaterally, translaminar screw acceptance rates in C3 and C5-C6 were significantly larger between Korean and American male population, but the rates in C3-C7 were similar between Korean and American female population.
Conclusion
The feasibility of unilateral and bilateral translaminar screw placement is different depending on different ethnics. Subaxial cervical unilateral translaminar screw placement among Korean male population and bilateral placement at C4-C7 among Korean female population are more acceptable than American population.
doi:10.3349/ymj.2015.56.1.159
PMCID: PMC4276750  PMID: 25510760
Translaminar; cervical fusion; cervical spine; ethics; Korean; American
10.  Anthocyanin Induces Apoptosis of DU-145 Cells In Vitro and Inhibits Xenograft Growth of Prostate Cancer 
Yonsei Medical Journal  2014;56(1):16-23.
Purpose
To investigate the effects of anthocyanins extracted from black soybean, which have antioxidant activity, on apoptosis in vitro (in hormone refractory prostate cancer cells) and on tumor growth in vivo (in athymic nude mouse xenograft model).
Materials and Methods
The growth and viability of DU-145 cells treated with anthocyanins were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and apoptosis was assessed by DNA laddering. Immunoblotting was conducted to evaluate differences in the expressions of p53, Bax, Bcl, androgen receptor (AR), and prostate specific antigen (PSA). To study the inhibitory effects of anthocyanins on tumor growth in vivo, DU-145 tumor xenografts were established in athymic nude mice. The anthocyanin group was treated with daily oral anthocyanin (8 mg/kg) for 14 weeks. After 2 weeks of treatment, DU-145 cells (2×106) were inoculated subcutaneously into the right flank to establish tumor xenografts. Tumor dimensions were measured twice a week using calipers and volumes were calculated.
Results
Anthocyanin treatment of DU-145 cells resulted in 1) significant increase in apoptosis in a dose-dependent manner, 2) significant decrease in p53 and Bcl-2 expressions (with increased Bax expression), and 3) significant decrease in PSA and AR expressions. In the xenograft model, anthocyanin treatment significantly inhibit tumor growth.
Conclusion
This study suggests that anthocyanins from black soybean inhibit the progression of prostate cancer in vitro and in a xenograft model.
doi:10.3349/ymj.2015.56.1.16
PMCID: PMC4276751  PMID: 25510742
Prostatic neoplasms; anthocyanins; apoptosis
11.  Various Applications of Deep Temporal Fascia in Rhinoplasty 
Yonsei Medical Journal  2014;56(1):167-174.
Purpose
In Asians, nasal dorsal and tip augmentation procedures are usually performed at the same time, and most dorsal augmentations use implants. In this study, dorsal augmentation was given by various types of grafts using deep temporal fascia (DTF) for primary rhinoplasty cases using only autologous tissues to improve the curve of hump noses and depressions. For secondary rhinoplasty cases, DTF was used to improve implant demarcation and transparency. Such effectiveness and utility of DTF is discussed.
Materials and Methods
Between May 2009 and May 2012, we performed rhinoplasty using DTF in 175 patients, which included 78 secondary surgery patients and 128 female patients. The mean age of the patients was 31.4. DTF was utilized with various types of grafts without implants to improve the curve in dorsal augmentation of hump noses and cases that required curve betterment. DTF was used to improve implant demarcation and transparency for secondary cases.
Results
The mean follow-up duration was 1.5 years. Of the 175 patients, 81% were satisfied with the natural correction achieved, whereas 19% complained of undercorrection, which was resolved with additional surgery. No specific complications such as nasal inflammation or contractures were observed.
Conclusion
DTF can be used with various graft methods for correction of radix, dorsal, and tip irregularities. It can also be used to correct implant contour transparency in secondary rhinoplasty and thus may be considered as a useful supplementary graft material in rhinoplasty for Asians.
doi:10.3349/ymj.2015.56.1.167
PMCID: PMC4276752  PMID: 25510761
Deep temporal fascia; rhinoplasty
12.  Clinical Implications of Microsatellite Instability in T1 Colorectal Cancer 
Yonsei Medical Journal  2014;56(1):175-181.
Purpose
The estimation of regional lymph node metastasis (LNM) risk in T1 colorectal cancer is based on histologic examination and imaging of the primary tumor. High-frequency microsatellite instability (MSI-H) is likely to decrease the possibility of metastasis to either regional lymph nodes or distant organs in colorectal cancers. This study evaluated the clinical implications of MSI in T1 colorectal cancer with emphasis on the usefulness of MSI as a predictive factor for regional LNM.
Materials and Methods
A total of 133 patients who underwent radical resection for T1 colorectal cancer were included. Genomic DNA was extracted from normal and tumor tissues and amplified by polymerase chain reaction (PCR). Five microsatellite markers, BAT-25, BAT-26, D2S123, D5S346, and D17S250, were used. MSI and clinicopathological parameters were evaluated as potential predictors of LNM using univariate and multivariate analyses.
Results
Among 133 T1 colorectal cancer patients, MSI-H, low-frequency microsatellite instability (MSI-L), and microsatellite stable (MSS) colorectal cancers accounted for 7.5%, 6%, and 86.5%, respectively. MSI-H tumors showed a female predominance, a proximal location and more retrieved lymph nodes. Twenty-two patients (16.5%) had regional LNM. Lymphovascular invasion and depth of invasion were significantly associated with LNM. There was no LNM in 10 MSI-H patients; however, MSI status was not significantly correlated with LNM. Disease-free survival did not differ between patients with MSI-H and those with MSI-L/MSS.
Conclusion
MSI status could serve as a negative predictive factor in estimating LNM in T1 colorectal cancer, given that LNM was not detected in MSI-H patients. However, validation of our result in a different cohort is necessary.
doi:10.3349/ymj.2015.56.1.175
PMCID: PMC4276753  PMID: 25510762
Microsatellite instability; lymph node metastasis; early colorectal cancer; T1; prognosis
13.  Overcoming the Limitations of Fine Needle Aspiration Biopsy: Detection of Lateral Neck Node Metastasis in Papillary Thyroid Carcinoma 
Yonsei Medical Journal  2014;56(1):182-188.
Purpose
Ultrasound (US) and US-guided fine needle aspiration biopsies (FNAB) are considered the modalities of choice for assessing lymph nodes suspected of containing metastases, but the sensitivity of FNAB varies and is specific to the operator. We analyzed the risk of FNAB providing false negative results of lateral neck node metastasis, and evaluated diagnostic accuracy of FNAB, in patients with papillary thyroid cancer.
Materials and Methods
FNAB was performed in 242 patients suspected of having lateral neck node metastasis on preoperative imaging. Thyroglobulin in the fine-needle aspirate washout (FNA wash-out Tg) and computed tomography enhancement (Hounsfield units) were measured. Patients with negative results on FNAB were examined by intraoperative frozen section. The false negative and true negative groups were compared.
Results
Of the 242 patients, 130 were confirmed as having lateral neck node metastases. In 74 patients, the metastasis was identified by FNAB. False positive results were observed in 2 patients (0.8%) and false negatives in 58 (44.6%). Risk analysis showed that patient age <45 years (p=0.006), tumor size >1 cm (p=0.008) and elevated FNA wash-out Tg (p=0.004) were significantly associated with false negative results on FNAB. The accuracy of FNAB increased significantly when combined with FNA wash-out Tg (p=0.003).
Conclusion
To reduce the false negative rate of FNAB, patient age (<45 years), tumor size (>1 cm) and FNA wash-out Tg (>34.8 ng/mL) should be considered in preoperative planning. Accuracy may be improved by combining the results of FNAB and FNA wash-out Tg.
doi:10.3349/ymj.2015.56.1.182
PMCID: PMC4276754  PMID: 25510763
Papillary thyroid carcinoma; metastasis
14.  The First Experiences of Robotic Single-Site Cholecystectomy in Asia: A Potential Way to Expand Minimally-Invasive Single-Site Surgery? 
Yonsei Medical Journal  2014;56(1):189-195.
Purpose
Herein, we firstly present the robotic single-site cholecystectomy (RSSC) as performed in Asia and evaluate whether it could overcome the limitations of conventional laparoscopic single-site cholecystectomy.
Materials and Methods
From October 2013 to November 2013, RSSC for benign gallbladder (GB) disease was firstly performed consecutively in five patients. We evaluated these early experiences of RSSC and compared factors including clinicopathologic factors and operative outcomes with our initial cases of single-fulcrum laparoscopic cholecystectomy (SFLC).
Results
Four female patients and one male patient underwent RSSC. Neither open conversion nor bile duct injury or bile spillage was noted during surgery. In comparisons with SFLC, patient-related factors in terms of age, sex, Body Mass Index, diagnosis, and American Society of Anesthesiologist score showed no significant differences between two groups. There were no significant differences in the operative outcomes regarding intraoperative blood loss, bile spillage during operation, postoperative pain scale values, postoperative complications, and hospital stay between the two groups (p<0.05). Actual dissection time (p=0.003) and total operation time (p=0.001) were significantly longer in RSSC than in SFLC. There were no drain insertion or open conversion cases in either group.
Conclusion
RSSC provides a comfortable environment and improved ergonomics to laparoscopic single-site cholecystectomy; however, this technique needs to be modified to allow for more effective intracorporeal movement. As experience and technical innovations continue, RSSC will soon be alternative procedure for well-selected benign GB disease.
doi:10.3349/ymj.2015.56.1.189
PMCID: PMC4276755  PMID: 25510764
Robotic; single-site; single port; cholecystectomy
15.  Attenuation of Peripheral Regulatory T-Cell Suppression of Skin-Homing CD8+T Cells in Atopic Dermatitis 
Yonsei Medical Journal  2014;56(1):196-203.
Purpose
Cutaneous lymphocyte-associated antigen (CLA)-expressing CD8+T cells have been known to play an important role in the pathogenesis of atopic dermatitis (AD). However, the mechanisms underlying the loss of self-tolerance remain unclear. Regulatory T cells (Tregs) play a key role in the development of homeostasis in the immune system. We, therefore, hypothesized that a reduced ability of Tregs to inhibit autologous CD8+CLA+T cells might be underlying mechanism in AD.
Materials and Methods
CD8+CLA+T cells and Tregs were obtained from the peripheral blood of AD patients and control volunteers. The frequencies of CD8+CLA+T cells were evaluated. The proliferative responses of CD8+CLA+T cells were assessed by flow cytometry, and the levels of transforming growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) in culture supernatants were detected by enzyme-linked immunosorbent assay.
Results
Our results revealed higher frequency and increased expression of perforin and granzyme-B in peripheral CD8+CLA+T cells in AD, and lower inhibitory ability of Tregs on proliferation of CD8+CLA+T cells in AD. Meanwhile, the levels of TGF-β1 produced by Tregs were significantly lower in AD, and anti-TGF-β1 abolished such suppression.
Conclusion
The attenuated inhibitory ability of Tregs on hyper-activated autologous CD8+CLA+T cells, mediated by TGF-β1, plays an important role in the pathogenesis of AD.
doi:10.3349/ymj.2015.56.1.196
PMCID: PMC4276756  PMID: 25510765
Cutaneous lymphocyte-associated antigen; CD8+T cell; regulatory; T cells; atopic dermatitis
16.  NGF and HB-EGF: Potential Biomarkers that Reflect the Effects of Fesoterodine in Patients with Overactive Bladder Syndrome 
Yonsei Medical Journal  2014;56(1):204-211.
Purpose
To determine whether levels of nerve growth factor (NGF) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) can be used to objectively assess overactive bladder syndrome (OAB) treatment outcome and to evaluate the effects of fixed-dose fesoterodine on OAB symptoms.
Materials and Methods
This study included 124 participants (62 patients with OAB and 62 controls) in Severance Hospital between 2010 and 2012. In patients with OAB, 4 mg fesoterodine was administered once daily. Repeated evaluations of putative biomarker levels, urine creatinine (Cr) levels, and questionnaire responses, including the Overactive Bladder Symptom Score (OABSS) and the Overactive Bladder Questionnaire (OAB q), were performed from baseline to 16 weeks.
Results
Urinary levels of NGF/Cr (OAB: 1.13±0.9 pg/mg; control: 0.5±0.29 pg/mg) and HB-EGF/Cr (OAB: 8.73±6.55 pg/mg; control: 4.45±2.93 pg/mg) were significantly higher in subjects with OAB than in controls (p<0.001). After 16 weeks of fixed-dose fesoterodine treatment, urinary NGF/Cr levels (baseline: 1.13±0.08 pg/mg; 16 weeks: 0.60±0.4 pg/mg; p=0.02) and HB-EGF/Cr levels significantly decreased (baseline: 8.73±6.55 pg/mg; 16 weeks: 4.72±2.69 pg/mg; p=0.03, respectively). Both the OABSS and OAB q scores improved (p<0.001). However, there were no a statistically significant correlations between these urinary markers and symptomatic scores.
Conclusion
Urinary levels of NGF and HB-EGF may be potential biomarkers for evaluating outcome of OAB treatment. Fixed-dose fesoterodine improved OAB symptoms. Future studies are needed to further examine the significance of urinary NGF and HB-EGF levels as therapeutic markers for OAB.
doi:10.3349/ymj.2015.56.1.204
PMCID: PMC4276757  PMID: 25510766
Heparin-binding EGF-like growth factor; nerve growth factor; overactive bladder; questionnaire; urinary biomarkers
17.  Efficacy of Veno-Venous Extracorporeal Membrane Oxygenation in Severe Acute Respiratory Failure 
Yonsei Medical Journal  2014;56(1):212-219.
Purpose
The objective of this study was to evaluate our institutional experience with veno-venous (VV) extracorporeal membrane oxygenation (ECMO) in patients with severe acute respiratory failure (ARF).
Materials and Methods
From January 2007 to August 2013, 31 patients with severe ARF that was due to various causes and refractory to mechanical ventilation with conventional therapy were supported with VV ECMO. A partial pressure of arterial oxygen (PaO2)/inspired fraction of oxygen (FiO2) <100 mm Hg at an FiO2 of 1.0 or a pH <7.25 due to CO2 retention were set as criteria for VV ECMO.
Results
Overall, 68% of patients survived among those who had received VV ECMO with a mean PaO2/FiO2 of 56.8 mm Hg. Furthermore, in trauma patients, early use of ECMO had the best outcome with a 94% survival rate.
Conclusion
VV ECMO is an excellent, life-saving treatment option in patients suffering from acute and life-threatening respiratory failure due to various causes, especially trauma, and early use of VV ECMO therapy improved outcomes in these patients.
doi:10.3349/ymj.2015.56.1.212
PMCID: PMC4276758  PMID: 25510767
Acute respiratory failure; extracorporeal membrane oxygenation; mechanical ventilation; survival rate
18.  Epidemiology of Trauma Patients and Analysis of 268 Mortality Cases: Trends of a Single Center in Korea 
Yonsei Medical Journal  2014;56(1):220-226.
Purpose
There is an increasing incidence of mortality among trauma patients; therefore, it is important to analyze the trauma epidemiology in order to prevent trauma death. The authors reviewed the trauma epidemiology retrospectively at a regional emergency center of Korea and evaluated the main factors that led to trauma-related deaths.
Materials and Methods
A total of 17007 trauma patients were registered to the trauma registry of the regional emergency center at Wonju Severance Christian Hospital in Korea from January 2010 to December 2012.
Results
The mean age of patients was 35.2 years old. The most frequent trauma mechanism was blunt injury (90.8%), as well as slip-and-fall down injury, motor vehicle accidents, and others. Aside from 142 early trauma deaths, a total of 4673 patients were admitted for further treatment. The most common major trauma sites of admitted patients were on the extremities (38.4%), followed by craniocerebral, abdominopelvis, and thorax. With deaths of 126 patients during in-hospital treatment, the overall mortality (142 early and 126 late deaths) was 5.6% for admitted patients. Ages ≥55, injury severity score ≥16, major craniocerebral injury, cardiopulmonary resuscitation at arrival, probability of survival <25% calculated from the trauma and injury severity score were independent predictors of trauma mortality in multivariate analysis.
Conclusion
The epidemiology of the trauma patients studied was found to be mainly blunt trauma. This finding is similar to previous papers in terms of demographics and mechanism. Trauma patients who have risk factors of mortality require careful management in order to prevent trauma-related deaths.
doi:10.3349/ymj.2015.56.1.220
PMCID: PMC4276759  PMID: 25510768
Trauma; epidemiology; mortality; injury severity score; predictor
19.  A Polymorphism of the Renin Gene rs6682082 Is Associated with Essential Hypertension Risk and Blood Pressure Levels in Korean Women 
Yonsei Medical Journal  2014;56(1):227-234.
Purpose
The aim of the present study was to investigate associations between the renin gene (REN) and the risk of essential hypertension and blood pressure (BP) levels in Koreans.
Materials and Methods
To outline the functional role of a single nucleotide polymorphism in the transcription of the REN gene, we conducted a case-control study of 1975 individuals: 646 hypertension (HT) patients and 1329 ethnically and age-matched normotensive subjects.
Results
Logistic regression analysis indicated that the genotypes AA/AG were strongly associated with risk of HT (odds ratio, 1.493; 95% confidence interval, 1.069-2.086, p=0.018) in female subjects. The genotypes AA/AG also showed significant association with higher blood pressure levels, both systolic and diastolic, in postmenopausal HT women (p=0.003 and p=0.017, respectively). Analysis of the promoter containing rs6682082 revealed a 2.4±0.01-fold higher activity in the A variant promoter than the G variant promoter, suggesting that rs6682082 is itself a functional variant.
Conclusion
We suggest that the A allele of rs6682082 is a positive genetic marker for predisposition to essential hypertension and high BP in Korean women and may be mediated through the transcriptional activation of REN.
doi:10.3349/ymj.2015.56.1.227
PMCID: PMC4276760  PMID: 25510769
Essential hypertension; renin; polymorphism; association
20.  The Effects of Different Noise Types on Heart Rate Variability in Men 
Yonsei Medical Journal  2014;56(1):235-243.
Purpose
To determine the impact of noise on heart rate variability (HRV) in men, with a focus on the noise type rather than on noise intensity.
Materials and Methods
Forty college-going male volunteers were enrolled in this study and were randomly divided into four groups according to the type of noise they were exposed to: background, traffic, speech, or mixed (traffic and speech) noise. All groups except the background group (35 dB) were exposed to 45 dB sound pressure levels. We collected data on age, smoking status, alcohol consumption, and disease status from responses to self-reported questionnaires and medical examinations. We also measured HRV parameters and blood pressure levels before and after exposure to noise. The HRV parameters were evaluated while patients remained seated for 5 minutes, and frequency and time domain analyses were then performed.
Results
After noise exposure, only the speech noise group showed a reduced low frequency (LF) value, reflecting the activity of both the sympathetic and parasympathetic nervous systems. The low-to-high frequency (LF/HF) ratio, which reflected the activity of the autonomic nervous system (ANS), became more stable, decreasing from 5.21 to 1.37; however, this change was not statistically significant.
Conclusion
These results indicate that 45 dB(A) of noise, 10 dB(A) higher than background noise, affects the ANS. Additionally, the impact on HRV activity might differ according to the noise quality. Further studies will be required to ascertain the role of noise type.
doi:10.3349/ymj.2015.56.1.235
PMCID: PMC4276761  PMID: 25510770
Autonomic nervous system; heart rate variability; noise
21.  Adjuvant Radiotherapy Outcome of Stage I Testicular Seminoma: A Single Institution Study 
Yonsei Medical Journal  2014;56(1):24-30.
Purpose
To analyze treatment outcome and side effects of adjuvant radiotherapy using radiotherapy fields and doses which have evolved over the last two decades in a single institution.
Materials and Methods
Forty-one patients received radiotherapy after orchiectomy from 1996 to 2007. At our institution, the treatment field for stage I seminoma has changed from dog-leg (DL) field prior to 2003 to paraaortic (PA) field after 2003. Fifteen patients were treated with the classic fractionation scheme of 25.5 Gy at 1.5 Gy per fraction. Other patients had been treated with modified schedules of 25.05 Gy at 1.67 Gy per fraction (n=15) and 25.2 Gy at 1.8 Gy per fraction (n=11).
Results
With a median follow-up of 112 months, the 5-year and 10-year survival rates were 100% and 96%, respectively, and 5-year and 10-year relapse-free survival rates were both 97.1%. No in-field recurrence occurred. Contralateral seminoma occurred in one patient 5 years after treatment. No grade III-IV acute toxicity occurred. An increased rate of grade 1-2 acute hematologic toxicity was found in patients with longer overall treatment times due to 1.5 Gy per fraction. The rate of grade 2 acute gastrointestinal toxicity was significantly higher with DL field than with PA field and also higher in the 1.8-Gy group than in the 1.5-Gy and 1.67-Gy groups.
Conclusion
Patients with stage I seminoma were safely treated with PA-only radiotherapy with no pelvic failure. Optimal fractionation schedule needs to be explored further in order to minimize treatment-related toxicity.
doi:10.3349/ymj.2015.56.1.24
PMCID: PMC4276762  PMID: 25510743
Testicular seminoma; para-aortic radiotherapy; late complication; secondary malignancy
22.  Effects of Diabetic Case Management on Knowledge, Self-Management Abilities, Health Behaviors, and Health Service Utilization for Diabetes in Korea 
Yonsei Medical Journal  2014;56(1):244-252.
Purpose
This study aimed to evaluate the effects of a case management program for diabetics, using a pre-post comparison design.
Materials and Methods
The study population comprised 6007 diabetics who received case management intervention in 2006 and were sampled nationwide in Korea. Before and after the intervention, the study population answered questions regarding their knowledge of diabetes, self-management ability, and health behaviors. Body mass index (BMI) was also calculated. Healthcare service utilization for diabetes was extracted from health insurance claim data from 2005 to 2007.
Results
The case management program significantly improved the study population's knowledge of diabetes and ability to self-manage nutrition, blood glucose monitoring, foot and oral care, and medications. This program also significantly changed the study population's health behaviors regarding smoking, alcohol drinking, and exercise, and BMI was positively affected. In the over-serviced subgroup, there was a significant decrease in the number of consultations (mean=7.0; SD=19.5) after intervention. Conversely, in the under-serviced subgroup, there was a significant increase in the number of consultations (mean=3.2; SD=7.9) and the days of prescribed medication (mean=66.4; SD=120.3) after intervention.
Conclusion
This study showed that the case management program led the study population to improve their knowledge, self-management ability, health behaviors, and utilization of health care. It is necessary in future studies to evaluate the appropriateness of healthcare usage and clinical outcome by using a control group to determine the direct effectiveness of this case management program.
doi:10.3349/ymj.2015.56.1.244
PMCID: PMC4276763  PMID: 25510771
Case management; diabetes; intervention; Korea
23.  Quantitative Analysis of the Effect of Iterative Reconstruction Using a Phantom: Determining the Appropriate Blending Percentage 
Yonsei Medical Journal  2014;56(1):253-261.
Purpose
To investigate the optimal blending percentage of adaptive statistical iterative reconstruction (ASIR) in a reduced radiation dose while preserving a degree of image quality and texture that is similar to that of standard-dose computed tomography (CT).
Materials and Methods
The CT performance phantom was scanned with standard and dose reduction protocols including reduced mAs or kVp. Image quality parameters including noise, spatial, and low-contrast resolution, as well as image texture, were quantitatively evaluated after applying various blending percentages of ASIR. The optimal blending percentage of ASIR that preserved image quality and texture compared to standard dose CT was investigated in each radiation dose reduction protocol.
Results
As the percentage of ASIR increased, noise and spatial-resolution decreased, whereas low-contrast resolution increased. In the texture analysis, an increasing percentage of ASIR resulted in an increase of angular second moment, inverse difference moment, and correlation and in a decrease of contrast and entropy. The 20% and 40% dose reduction protocols with 20% and 40% ASIR blending, respectively, resulted in an optimal quality of images with preservation of the image texture.
Conclusion
Blending the 40% ASIR to the 40% reduced tube-current product can maximize radiation dose reduction and preserve adequate image quality and texture.
doi:10.3349/ymj.2015.56.1.253
PMCID: PMC4276764  PMID: 25510772
CT Image quality; iterative reconstruction; filtered back projection; radiation dose reduction; texture analysis
24.  Characteristics of Inpatient Care and Rehabilitation for Acute First-Ever Stroke Patients 
Yonsei Medical Journal  2014;56(1):262-270.
Purpose
The purpose of this study was to analyze the status of inpatient care for acute first-ever stroke at three general hospitals in Korea to provide basic data and useful information on the development of comprehensive and systematic rehabilitation care for stroke patients.
Materials and Methods
This study conducted a retrospective complete enumeration survey of all acute first-ever stroke patients admitted to three distinct general hospitals for 2 years by reviewing medical records. Both ischemic and hemorrhagic strokes were included. Survey items included demographic data, risk factors, stroke type, state of rehabilitation treatment, discharge destination, and functional status at discharge.
Results
A total of 2159 patients were reviewed. The mean age was 61.5±14.4 years and the ratio of males to females was 1.23:1. Proportion of ischemic stroke comprised 54.9% and hemorrhagic stroke 45.1%. Early hospital mortality rate was 8.1%. Among these patients, 27.9% received rehabilitation consultation and 22.9% underwent inpatient rehabilitation treatment. The mean period from admission to rehabilitation consultation was 14.5 days. Only 12.9% of patients were transferred to a rehabilitation department and the mean period from onset to transfer was 23.4 days. Improvements in functional status were observed in the patients who had received inpatient rehabilitation treatment after acute stroke management.
Conclusion
Our analysis revealed that a relatively small portion of patients who suffered from an acute first-ever stroke received rehabilitation consultation and inpatient rehabilitation treatment. Thus, applying standardized clinical practice guidelines for post-acute rehabilitation care is needed to provide more effective and efficient rehabilitation services to patients with stroke.
doi:10.3349/ymj.2015.56.1.262
PMCID: PMC4276765  PMID: 25510773
Stroke; inpatients; acute management; rehabilitation; Korea
25.  Reliability and Validity of the Upper Limb Physician's Rating Scale in Children with Cerebral Palsy 
Yonsei Medical Journal  2014;56(1):271-276.
Purpose
The Upper Limb Physician's Rating Scale (ULPRS) is a tool that assesses movement quality of the upper limbs. It is used as an outcome measure after botulinum toxin type A injection in children with cerebral palsy (CP). This study aimed to investigate the reliability and validity of the ULPRS in children with spastic CP.
Materials and Methods
Thirty children with spastic CP (M:F=17:13) aged 5 to 13 years old were recruited. The ULPRS was scored based on recorded videotapes by four physicians on two separate occasions. The Melbourne Assessment of Unilateral Upper Limb Function (MUUL) was scored by an occupational therapist. Intraclass correlation coefficients (ICCs), 95% confidence intervals and weighted kappa statistics were calculated for the scores of ULPRS to obtain interrater and intrarater reliability. The relationship between ULPRS and MUUL was assessed using Pearson correlation coefficients.
Results
The ICCs for the total ULPRS scores were 0.94 between raters and 0.99 to 1.00 within raters. The weighted kappa statistics for subitem scores for the ULPRS ranged from 0.67 to 1.00 within raters and from 0.46 to 0.86 between raters. The relationship between ULPRS and MUUL was strong (Pearson correlation coefficient=0.751; p<0.05).
Conclusion
The results demonstrated the high reliability of the total ULPRS score within and between raters. A significant concurrent validity between ULPRS and MUUL also supports the clinical utility of the ULPRS as an outcome measure of spastic upper limb in children with CP.
doi:10.3349/ymj.2015.56.1.271
PMCID: PMC4276766  PMID: 25510774
Upper extremity; botulinum toxin type A injection; outcome measure; Melbourne assessment; unilateral upper limb function

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