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1.  Difference of Sagittal Spinopelvic Alignments between Degenerative Spondylolisthesis and Isthmic Spondylolisthesis 
Objective
The purpose of this study was to analyze the differences of spinopelvic parameters between degenerative spondylolisthesis (DSPL) and isthmic spondylolisthesis (ISPL) patients.
Methods
Thirty-four patients with DSPL and 19 patients with ISPL were included in this study. Spinopelvic parameters were evaluated on whole spine X-rays in a standing position. The following spinopelvic parameters were measured : pelvic incidence (PI), sacral slope, pelvic tilt (PT), lumbar lordosis (LL), and sagittal vertical axis from C7 plumb line (SVA). The population of patients was compared with a control population of 30 normal and asymptomatic adults.
Results
There were statistically significant differences in LL (p=0.004) and SVA (p=0.005) between the DSPL and ISPL group. The LL of DSPL (42±13°) was significantly lower than that of the control group (48±11°; p=0.029), but that of ISPL (55±6°) was significantly greater than a control group (p=0.004). The SVA of DSPL (55±49 mm) was greater than that of a control group (<40 mm), but that of ISPL (21±22 mm) was within 40 mm as that of a control group. The PT of DSPL (24±7°) and ISPL (21±7°) was significantly greater than that of a control group (11±6°; p=0.000).
Conclusion
Both symptomatic DSPL and ISPL patients had a greater PI than that of the asymptomatic control group. In conclusion, DSPL populations are likely to have global sagittal imbalance (high SVA) compared with ISPL populations because of the difference of lumbar lordosis between two groups.
doi:10.3340/jkns.2013.53.2.96
PMCID: PMC3611066  PMID: 23560173
Spinopelvic alignment; Pelvic incidence; Lumbar lordosis; Degenerative spondylolisthesis; Isthmic spondylolisthesis
2.  Association Study of Fibroblast Growth Factor 2 and Fibroblast Growth Factor Receptors Gene Polymorphism in Korean Ossification of the Posterior Longitudinal Ligament Patients 
Objective
The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) of fibroblast growth factor (FGF) 2 gene and fibroblast growth factor receptor (FGFR) genes are associated with ossification of the posterior longitudinal ligament (OPLL).
Methods
A total of 157 patients with OPLL and 222 controls were recruited for a case control association study investigating the relationship between SNPs of FGF2, FGFR1, FGFR2 and OPLL. To identify the association among polymorphisms of FGF2 gene, FGFR1, FGFR2 genes and OPLL, the authors genotyped 9 SNPs of the genes (FGF2 : rs1476217, rs308395, rs308397, and rs3747676; FGFR1 : rs13317 and rs2467531; FGFR2 : rs755793, rs1047100, and rs3135831) using direct sequencing method. SNPs data were analyzed using the SNPStats, SNPAnalyzer, Haploview, and Helixtree programs.
Results
Of the SNPs, a SNP (rs13317) in FGFR1 was significantly associated with the susceptibility of OPLL in the codominant (odds ratio=1.35, 95% confidence interval=1.01-1.81, p=0.048) and recessive model (odds ratio=2.00, 95% confidence interval=1.11-3.59, p=0.020). The analysis adjusted for associated condition showed that the SNP of rs1476217 (p=0.03), rs3747676 (p=0.01) polymorphisms in the FGF2 were associated with diffuse idiopathic skeletal hyperostosis (DISH) and rs1476217 (p=0.01) in the FGF2 was associated with ossification of the ligament flavum (OLF).
Conclusion
The results of the present study revealed that an FGFR1 SNP was significantly associated with OPLL and that a SNP in FGF2 was associated with conditions that were comorbid with OPLL (DISH and OLF).
doi:10.3340/jkns.2012.52.1.7
PMCID: PMC3440509  PMID: 22993671
OPLL; FGF2 gene; FGFR 1 & 2 genes; Polymorphism
3.  Lumbar Interbody Fusion Outcomes in Degenerative Lumbar Disease : Comparison of Results between Patients Over and Under 65 Years of Age 
Objective
To evaluate the clinical and radiological outcomes of lumbar interbody fusion and its correlation with various factors (e.g., age, comorbidities, fusion level, bone quality) in patients over and under 65 years of age who underwent lumbar fusion surgery for degenerative lumbar disease.
Methods
One-hundred-thirty-three patients with lumbar degenerative disease underwent lumbar fusion surgery between June 2006 and June 2007 and were followed for more than one year. Forty-eight (36.1%) were older than 65 years of age (group A) and 85 (63.9%) were under 65 years of age (group B). Diagnosis, comorbidities, length of hospital stay, and perioperative complications were recorded. The analysis of clinical outcomes was based on the visual analogue scale (VAS). Radiological results were evaluated using plain radiographs. Clinical outcomes, radiological outcomes, length of hospital stay, and complication rates were analyzed in relation to lumbar fusion level, the number of comorbidities, bone mineral density (BMD), and age.
Results
The mean age of the patients was 61.2 years (range, 33-86 years) and the mean BMD was -2.2 (range, -4.8 to -2.8). The mean length of hospital stay was 15.0 days (range, 5-60 days) and the mean follow-up was 23.0 months (range, 18-30 months). Eighty-five (64.0%) patients had more than one preoperative comorbidities. Perioperative complications occurred in 27 of 133 patients (20.3%). The incidence of overall complication was 22.9% in group A, and 18.8% in group B but there was no statistical difference between the two groups. The mean VAS scores for the back and leg were significantly decreased in both groups (p < 0.05), and bony fusion was achieved in 125 of 133 patients (94.0%). There was no significant difference in bony union rates between groups A and B (91.7% in group A vs. 95.3% in group B, p = 0.398). In group A, perioperative complications were more common with the increase in fusion level (p = 0.027). Perioperative complications in both groups A (p = 0.035) and B (p = 0.044) increased with an increasing number of comorbidities.
Conclusion
Elderly patients with comorbidities are at a high risk for complications and adverse outcomes after lumbar spine surgery. In our study, clinical outcomes, fusion rates, and perioperative complication rates in older patients were comparable with those in younger populations. The number of comorbidities and the extent of fusion level were significant factors in predicting the occurrence of postoperative complications. However, proper perioperative general supportive care with a thorough fusion strategy during the operation could improve the overall postoperative outcomes in lumbar fusion surgery for elderly patients.
doi:10.3340/jkns.2010.48.5.412
PMCID: PMC3030080  PMID: 21286477
Elderly patients; Lumbar interbody fusion; Comorbidities; Complications
4.  Total En Bloc Lumbar Spondylectomy of Follicular Thyroid Carcinoma 
The presence of distant metastases from differentiated thyroid carcinoma decreases the 10-year survival rates of patients by 50%. This is a report of a 61-year-old female with follicular thyroid carcinoma who presented initially with low back pain. 2-deoxy-2-[18F] fluoro-D-glucose whole-body positron emission tomography/computed tomography (PET/CT) demonstrated a hypointensity lesion in the left thyroid gland with malignant uptake in L1 vertebra and magnetic resonance images revealed paravertebral and epidural extension of mass in L1 vertebra. After thyroidectomy, histopathological study showed a follicular carcinoma. We performed L1 total en bloc spondylectomy with expandable cage for long-term local control. The technical details of total en bloc spondylectomy in follicular carcinoma are described herein.
doi:10.3340/jkns.2009.45.3.188
PMCID: PMC2666124  PMID: 19352484
Thyroid carcinoma; Total en bloc spondylectomy; Metastasis
5.  Anterior Interbody Grafting and Instrumentation for Advanced Spondylodiscitis 
Objective
To evaluate the surgical outcomes of ventral interbody grafting and anterior or posterior spinal instrumentation for the treatment of advanced spondylodiscitis in patients who had failed medical management.
Methods
A total of 28 patients were evaluated for associated medical illness, detected pathogen, level of involved spine, and perioperative complications. Radiological evaluation including the rate of bony union, segmental Cobb angle, graft- and instrumentation-related complications, and clinical outcomes by mean Frankel scale and VAS score were performed.
Results
There are 14 pyogenic spondylodiscitis, 6 postoperative spondylodiscitis, and 8 tuberculous spondylodiscitis. There were 21 males and 7 females. Mean age was 51 years, with a range from 18 to 77. Mean follow-up period was 10.9 months. Associated medical illnesses were 6 diabetes, 3 pulmonary tuberculosis, and 4 chronic liver diseases. Staphylococcus was the most common pathogen isolated (25%), and Mycobacterium tuberculosis was found in 18% of the patients. Operative approaches, either anterior or posterior spinal instrumentation, were done simultaneously or delayed after anterior aggressive debridement, neural decompression, and structural interbody bone grafting. All patients with neurological deficits improved after operation, except only one who died from aggravation as military tuberculosis. Mean Frankel scale was changed from 3.78±0.78 preoperatively to 4.78±0.35 at final follow up and mean VAS score was improved from 7.43±0.54 to 2.07±1.12. Solid bone fusion was obtained in all patients except only one patient who died. There was no need for prolongation of duration of antibiotics and no evidence of secondary infection owing to spinal instrumentations.
Conclusion
According to these results, debridement and anterior column reconstruction with ventral interbody grafting and instrumentation is effective and safe in patients who had failed medical management and neurological deficits in advanced spondylodiscitis.
doi:10.3340/jkns.2008.43.1.5
PMCID: PMC2588159  PMID: 19096537
Advanced spondylodiscitis; Ventral interbody grafting; Spinal instrumentation
6.  Factors Associated With the Time to Next Attack in Neuromyelitis Optica: Accelerated Failure Time Models With Random Effects 
PLoS ONE  2013;8(12):e82325.
Background and Objective
Neuromyelitis optica (NMO) is an inflammatory demyelinating disorder of the central nervous system with a relapsing and remitting course. We aimed to identify factors associated with the time to next attack, including the effect of the natural disease course and the diverse treatment regimens, by applying a longitudinal statistical analysis to the individual attacks of each patient.
Methods
In total, 184 acute attacks among 58 patients with either NMO or NMO spectrum disorder with anti-aquaporin-4 antibody were assessed retrospectively. Patient demographics, clinical characteristics at each attack, and type of treatment during inter-attack periods were assessed. The dependent variable was defined as the time from each attack to the next attack (inter-attack interval). An exponential accelerated failure time model with shared gamma frailty was adapted for statistical analysis.
Results
A multivariable analysis revealed that the time from each attack to the next attack in NMO increased independently by 1.31 times (95% confidence interval (CI), 1.02–1.67; p = 0.035) with each additional cumulative attack experienced, by 5.34 times (95% CI, 1.57–18.13; p = 0.007) with combined azathioprine treatment and continued oral prednisolone, and by 4.26 times (95% CI, 1.09–16.61; p = 0.037) with rituximab treatment.
Conclusion
The time to next attack in NMO can increase naturally in the later stages of the disease as the number of cumulative attacks increases. Nevertheless, both combined azathioprine treatment with continued oral prednisolone and rituximab treatment were also associated with a longer time to next attack, independently of the natural disease course of NMO.
doi:10.1371/journal.pone.0082325
PMCID: PMC3864949  PMID: 24358171
7.  Outcome and Efficacy of Height Gain and Sagittal Alignment after Kyphoplasty of Osteoporotic Vertebral Compression Fractures 
Objective
Although a significant correction of local kyphosis has been reported previously, only a few studies have investigated whether this correction leads to an improved overall sagittal alignment. The study objective was to determine whether an improvement in the local kyphotic angle improves the overall sagittal alignment. We examined and compared the effects of thoracic and lumbar level kyphoplasty procedures on local versus overall sagittal alignment of the spine.
Methods
Thirty-eight patients with osteoporotic vertebral compression fractures who showed poor response to conventional, palliative medical therapy underwent single-level kyphoplasty. The pertinent clinical data of these patients, from June 2006 to November 2006, were reviewed retrospectively. We measured preoperative and postoperative vertebral body heights, which were classified as anterior, middle, or posterior fractured vertebral body heights. Furthermore, the local and overall sagittal angles after polymethylmethacrylate deposition were measured.
Results
More height was gained at the thoracic level, and the middle vertebral height regained the most. A significant local kyphosis correction was observed at the fractured level, and the correction at larger spanning segments decreased with the distance from the fractured level.
Conclusion
The inflatable balloon kyphoplasty procedure was the most effective in regaining the height of the thoracic fractured vertebra in the middle vertebral body. The kyphosis correction by kyphoplasty was mainly achieved in the fractured vertebral body. Sagittal angular correction decreased with an increase in the distance from the fractured vertebra. No significant improvement was observed in the overall sagittal alignment after kyphoplasty. Further studies in a larger population are required to clarify this issue.
doi:10.3340/jkns.2007.42.4.271
PMCID: PMC2588214  PMID: 19096555
Kyphoplasty; Vertebral compression fracture; Sagittal alignment
8.  Intermittent Hypoxia Can Aggravate Motor Neuronal Loss and Cognitive Dysfunction in ALS Mice 
PLoS ONE  2013;8(11):e81808.
Background
Patients with ALS may be exposed to variable degrees of chronic intermittent hypoxia. However, all previous experimental studies on the effects of hypoxia in ALS have only used a sustained hypoxia model and it is possible that chronic intermittent hypoxia exerts effects via a different molecular mechanism from that of sustained hypoxia. No study has yet shown that hypoxia (either chronic intermittent or sustained) can affect the loss of motor neurons or cognitive function in an in vivo model of ALS.
Objective
To evaluate the effects of chronic intermittent hypoxia on motor and cognitive function in ALS mice.
Methods
Sixteen ALS mice and 16 wild-type mice were divided into 2 groups and subjected to either chronic intermittent hypoxia or normoxia for 2 weeks. The effects of chronic intermittent hypoxia on ALS mice were evaluated using the rotarod, Y-maze, and wire-hanging tests. In addition, numbers of motor neurons in the ventral horn of the spinal cord were counted and western blot analyses were performed for markers of oxidative stress and inflammatory pathway activation.
Results
Compared to ALS mice kept in normoxic conditions, ALS mice that experienced chronic intermittent hypoxia had poorer motor learning on the rotarod test, poorer spatial memory on the Y-maze test, shorter wire hanging time, and fewer motor neurons in the ventral spinal cord. Compared to ALS-normoxic and wild-type mice, ALS mice that experienced chronic intermittent hypoxia had higher levels of oxidative stress and inflammation.
Conclusions
Chronic intermittent hypoxia can aggravate motor neuronal death, neuromuscular weakness, and probably cognitive dysfunction in ALS mice. The generation of oxidative stress with activation of inflammatory pathways may be associated with this mechanism. Our study will provide insight into the association of hypoxia with disease progression, and in turn, the rationale for an early non-invasive ventilation treatment in patients with ALS.
doi:10.1371/journal.pone.0081808
PMCID: PMC3841127  PMID: 24303073
9.  Cell-Free microRNA-214 From Urine as a Biomarker for Non-Muscle-Invasive Bladder Cancer 
Korean Journal of Urology  2013;54(11):791-796.
Purpose
MicroRNAs are small noncoding RNAs and microRNA-214 (miR-214) has been associated with the inhibition of cancer cell growth, migration, and invasion. The aim of this study was to investigate whether cell-free miR-214 isolated from urine could be used as a biomarker for non-muscle-invasive bladder cancer (NMIBC).
Materials and Methods
A total of 138 patients with primary NMIBC and 144 healthy normal controls were enrolled in this study. By use of quantitative polymerase chain reaction (PCR), the urinary levels of cell-free miR-214 were measured and the clinicopathological parameters of patients with NMIBC were compared with those of the controls.
Results
The urinary levels of cell-free miR-214 were significantly higher in the NMIBC patients than in the controls (20.08±3.21 vs. 18.96±2.68, p=0.002). However, the urinary levels of cell-free miR-214 were neither graded nor staged for the NMIBC patients (p>0.05, each). When we compared the urinary levels of cell-free miR-214 according to clinical outcomes, patients with recurrence had lower levels of miR-214 than did those with no recurrence (19.24±2.67 vs. 20.41±3.41, p=0.023). By contrast, there were no significant differences in the urinary level of cell-free miR-214 between the NMIBC patients showing progression and those showing no progression (p=0.919). Multivariate Cox regression analysis revealed that urinary levels of cell-free miR-214 were an independent predictor of NMIBC recurrence (hazard ratio, 2.011; 95% confidence interval, 1.027 to 3.937; p=0.041).
Conclusions
Urinary levels of cell-free miR-214 could be an independent prognostic parameter for NMIBC recurrence. Thus, urinary cell-free microRNA-214 might be a useful prognostic marker for NMI BC.
doi:10.4111/kju.2013.54.11.791
PMCID: PMC3830974  PMID: 24255763
MicroRNAs; Neoplasms; Recurrence; Urinary bladder
10.  Nocturnal Hypoxia in ALS Is Related to Cognitive Dysfunction and Can Occur as Clusters of Desaturations 
PLoS ONE  2013;8(9):e75324.
Background
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that leads to progressive weakness of the respiratory and limb muscles. Consequently, most patients with ALS exhibit progressive hypoventilation, which worsens during sleep. The aim of this study was to evaluate the relationship between nocturnal hypoxia and cognitive dysfunction and to assess the pattern of nocturnal hypoxia in patients with ALS.
Method
Twenty-five patients with definite or probable ALS underwent neuropsychologic testing, nocturnal pulse oximetry, and capnography. Patients were grouped according to the presence of nocturnal hypoxia (SpO2<95% for ≥10% of the night) and their clinical characteristics and cognitive function were compared.
Results
Compared to patients without nocturnal hypoxia, those with nocturnal hypoxia (n = 10, 40%) had poor memory retention (p = 0.039) and retrieval efficiency (p = 0.045). A cluster-of-desaturation pattern was identified in 7 patients (70%) in the Hypoxia Group.
Conclusions
These results suggest that nocturnal hypoxia can be related to cognitive dysfunction in ALS. In addition, a considerable number of patients with ALS may be exposed to repeated episodes of deoxygenation–reoxygenation (a cluster-of-desaturation pattern) during sleep, which could be associated with the generation of reactive oxygen species. Further studies are required to define the exact causal relationships between these phenomena, the exact manifestations of nocturnal cluster-of-desaturation patterns, and the effect of clusters of desaturation on ALS progression.
doi:10.1371/journal.pone.0075324
PMCID: PMC3776791  PMID: 24058674
11.  Intraoperative Neurophysiologic Monitoring: Basic Principles and Recent Update 
Journal of Korean Medical Science  2013;28(9):1261-1269.
The recent developments of new devices and advances in anesthesiology have greatly improved the utility and accuracy of intraoperative neurophysiological monitoring (IOM). Herein, we review the basic principles of the electrophysiological methods employed under IOM in the operating room. These include motor evoked potentials, somatosensory evoked potentials, electroencephalography, electromyography, brainstem auditory evoked potentials, and visual evoked potentials. Most of these techniques have certain limitations and their utility is still being debated. In this review, we also discuss the optimal stimulation/recording method for each of these modalities during individual surgeries as well as the diverse criteria for alarm signs.
doi:10.3346/jkms.2013.28.9.1261
PMCID: PMC3763097  PMID: 24015028
Intraoperative Neurophysiologic Monitoring; Evoked Potential; Guideline
12.  A Case of Thyrotoxic Myopathy with Extreme Type 2 Fiber Predominance 
Experimental Neurobiology  2013;22(3):232-234.
In hyperthyroidism, many patients had neuromuscular symptoms and clinical weakness correlated with free thyroxine (T4) concentrations. The common clinical symptoms of chronic thyrotoxic myopathy were characterized by progressive weakness in proximal muscles and atrophy. A 55-year old woman was visited our hospital with two years of progressive weakness of both legs. Physical examination showed diffuse enlargement of the thyroid gland, muscle atrophy and tachycardia. Motor examination showed proximal weakness in both legs. Serum creatine phosphokinase was normal and electromyography showed a myopathic pattern. Serum thyroxine (T4) was greatly increased and serum thyroid stimulating hormone was very low. Muscle biopsy showed mild atrophic change and type 2 fiber predominance. The patient's symptoms were improved during treatment with methimazole. Herein we report a case of thyrotoxic myopathy with extreme type 2 fiber predominance histologically.
doi:10.5607/en.2013.22.3.232
PMCID: PMC3807010  PMID: 24167418
thyrotoxic myopathy; hyperthyroidism; type 2 fiber
13.  Effect of Oxcarbazepine on Background EEG Activity and Cognition in Epilepsy 
Background and Purpose:
Cognitive dysfunction related to antiepileptic drugs (AEDs) is an important issue in the management of patients with epilepsy. The aim of the present study was to evaluate relative long-term effects of oxcarbazepine (OXC) on cognition in drug-naive patients with epilepsy.
Methods:
Fifteen drug-naïve epilepsy patients were enrolled. Electroencephalogram (EEG) recordings and neuropsychological (NP) tests were performed before and after OXC monotherapy. The relative power of the discrete frequency bandwas obtained. In addition, interhemispheric and intrahemispheric spectral coherence was also calculated.
Results:
NP tests showed significant improvement in visuo-spatial, memory and executive function after OXC treatment. However, neither spectral power nor coherence changed significantly with OXC treatment.
Conclusions:
Our study supports the notion that OXC has no significant cognitive side effect in patients with epilepsy.
doi:10.14581/jer.13002
PMCID: PMC3957317  PMID: 24649465
Epilepsy; Oxcarbazepine; Cognition; Quantitative EEG; Coherence
14.  Voluntary movements as a possible non-reflexive pain assay 
Molecular Pain  2013;9:25.
Background
The quantification of pain intensity in vivo is essential for identifying the mechanisms of various types of pain or for evaluating the effects of different analgesics. A variety of behavioral tests for pain measurement have been devised, but many are limited because animals are physically restricted, which affects pain sensation. In this study, pain assessment was attempted with minimal physical restriction, and voluntary movements of unrestrained animals were used to evaluate the intensities of various types of pain.
Results
The number of times animals reared or total distances traveled was measured using a motion-tracking device and found to be markedly reduced in carrageenan-induced inflammatory, acetic acid-induced visceral, and streptozotocin-induced neuropathic pain tests. These two voluntary movement parameters were found to be highly correlated with paw withdrawal latency from irradiating heat. In addition, these parameters were markedly reversed by morphine and by non-steroidal anti-inflammatory drugs in inflammatory pain models. These parameters were also useful to detect hypoalgesia in TRPV1-/- mice.
Conclusions
These results suggest that parameters of voluntary movement, such as, number of rearing and total distance moved, are effective indicators of pain intensity for many types of pain and that they can be used to evaluate degree of pain perception.
doi:10.1186/1744-8069-9-25
PMCID: PMC3716716  PMID: 23688027
Voluntary movement; Rearing; Total distance moved; Inflammatory pain; Neuropathic pain; Visceral pain; TRPV1
15.  Potential Immunoinflammatory Role of Staphylococcal Enterotoxin A in Atopic Dermatitis: Immunohistopathological Analysis and in vitro Assay 
Annals of Dermatology  2013;25(2):173-180.
Background
The underlying mechanism of atopic dermatitis (AD) exacerbated by Staphylococcus aureus has not been established. However, we demonstrated recently that the majority of S. aureus strains colonized in the skin of Korean AD patients carried genes encoding staphylococcal enterotoxin A (SEA) and/or toxic shock syndrome toxin-1 (TSST-1).
Objective
To clarify the role of staphylococcal superantigen, SEA in AD.
Methods
With the lesional skin of 9 AD patients and normal looking skin of one healthy adult, we examined first the expression of SEA, staphylococcal enterotoxin B (SEB), and TSST-1 using immunohistochemical analysis. In addition, we investigated the effects of SEA on the expression of inflammation-related adhesion molecules and cytokines in human HaCaT keratinocytes and Human Umbilical Vein Endothelial Cells (HUVECs) by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and enzyme-linked immunosorbent assay.
Results
Staphylococcal protein A (SPA) and SEA were detected with increased immunoreactivity in AD patients. However, TSST-1 showed mild-to-moderate immunoreactivity in AD patients, whereas SEB was minimally detected. In the double immunofluorescence investigation, SEA and SPA were well co-localized. SEA induced upregulation of adhesion molecules and elicited inflammatory responses in HaCaT keratinocytes and HUVECs.
Conclusion
This study demonstrates the importance of SEA as an immunoinflammatory triggering factor of AD in Koreans.
doi:10.5021/ad.2013.25.2.173
PMCID: PMC3662910  PMID: 23717008
Atopic dermatitis; Staphylococcal enterotoxin A; Staphylococcus aureus
16.  Evaluation of the angiogenesis inhibitor KR-31831 in SKOV-3 tumor-bearing mice using 64Cu-DOTA-VEGF121 and microPET☆ 
Nuclear medicine and biology  2012;39(6):840-846.
KR-31831 ((2R,3R,4S)-6-amino-4-[N-(4-chloropheyl)-N-(1H-imidazol-2ylmethyl)amino]-3-hydroxyl-2-methyl-2-dimethoxymethyl-3,4-dihydro-2H-1-benzopyran), an angiogenesis inhibitor, was evaluated in tumor-bearing mice using molecular imaging technology. Pre-treatment microPET images were acquired on SKOV-3 cell-implanted nude mice after injection with 64Cu-DOTA-VEGF121. KR-31831 (50 mg/kg) was then injected intraperitoneally into the treatment group (n=3), while injection vehicle was injected into the control (n=4) and blocking (n=3) groups. After injections occurred daily for 28 days, all groups of mice underwent post-treatment microPET imaging after injection with 64Cu-DOTA-VEGF121. The post-treatment images showed high tumor uptake in the control group and reduced tumor uptake in both the blocking and treatment groups. ROI analysis of the tumor images revealed 6.25%±1.18% ID/g at 1 h, 6.55%±0.69% ID/g at 2 h, and 4.68%±0.63% ID/g at 16 h in the control group; 3.87%±0.45% ID/g at 1 h, 4.50%±0.44% ID/g at 2 h, and 3.63%±0.25% ID/g at 16 h in the blocking group; and 4.03%±0.74% ID/g at 1 h, 4.37%±0.67% ID/g at 2 h, and 3.83%±0.90% ID/g at 16 h in the treatment group. Biodistribution obtained after the post-treatment microPET imaging also demonstrated high tumor uptake (3.74%±0.27% ID/g) in the control group and reduced uptakes in both the blocking group (2.69%±0.73% ID/g, P<.05) and the treatment group (3.11%±0.25% ID/g, P<.05), which correlated well with microPET imaging data. Immunofluorescence analysis showed higher levels of VEGFR2 and CD31 expressions in tumor tissues of the control and blocking groups than in tumor tissues of the treatment group. These results suggest that the antiangiogenic activity of KR-31831 is mediated through VEGFR2 and microPET serves as a useful molecular imaging tool for evaluation of a newly developed angiogenesis inhibitor, KR-31831.
doi:10.1016/j.nucmedbio.2012.01.007
PMCID: PMC3629961  PMID: 22406249
KR-31831; 64Cu-DOTA-VEGF121; MicroPET; VEGFR2; Angiogenesis
17.  Hypolipidemia in Patients with Amyotrophic Lateral Sclerosis: A Possible Gender Difference? 
Background and Purpose
We compared the levels of serum lipid, protein, and glucose between patients with amyotrophic lateral sclerosis (ALS) and healthy controls.
Methods
The serum levels of lipids [including triglycerides, cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL)], protein, and glucose of 95 patients with ALS (60 men) were compared with those of 99 age- and sex-matched healthy controls (64 men). Both groups had normal dietary intakes.
Results
Total cholesterol (p=0.004), LDL (p=0.040), triglyceride (p=0.025), and protein (p=0.010) levels, and LDL/HDL ratios (p<0.001) in men with ALS were significantly lower than those in their control counterparts. There were no such significant differences in these parameters between female patients with ALS and female controls.
Conclusions
The serum levels of lipid and protein were significantly lower in male patients with ALS than in the male controls. Since we controlled for the confounding effects of dietary intake, hypolipidemia in ALS might be associated with the pathophysiology of the disease rather than being the result of the decreased dietary intake in ALS patients. Metabolic demand might increase in ALS, and it may be affected by gender.
doi:10.3988/jcn.2013.9.2.125
PMCID: PMC3633190  PMID: 23626651
amyotrophic lateral sclerosis; dyslipidemia; gender differences
18.  Clinical Features of Symptomatic Meckel's Diverticulum in Children: Comparison of Scintigraphic and Non-scintigraphic Diagnosis 
Purpose
Meckel's diverticulum (MD) has various clinical manifestations, and diagnosis or selectection of proper diagnostic tools is not easy. This study was conducted in order to assess the clinical differences of MD diagnosed by scintigraphic and non-scintigraphic methods and to find the proper diagnostic tools.
Methods
We conducted a retrospective review ofthe clinical, surgical, radiologic, and pathologic findings of 34 children with symptomatic MD, who were admitted to Gachon University Gil Medical Center, Inha University Hospital, and The Catholic University of Korea, Incheon St. Mary's Hospital between January 2000 and December 2012. The patients were evaluated according to scintigraphic (12 cases; group 1) and non-scintigraphic (22 cases; group 2) diagnosis.
Results
The male to female ratio was 7.5 : 1. The most frequent chief complaint was lower gastrointestinal (GI) bleeding in group 1 and nonspecific abdominal pain in group 2, respectively. The most frequent pre-operative diagnosis was MD in both groups. Red blood cell (RBC) index was significantly lower in group 1. MD was located at 7 cm to 85 cm from the ileocecal valve. Four patients in group 1 had ectopic gastric tissues causing lower GI bleeding. The most frequent treatment modality was diverticulectomy in group 1 and ileal resection in group 2, respectively.
Conclusion
To diagnose MD might be delayed unless proper diagnostic tools are considered. It is important to understand indications of scintigraphic and non-scintigraphic methods according to clinical and hematologic features of MD. Scintigraphy would be weighed in patients with anemia as well as GI symptoms.
doi:10.5223/pghn.2013.16.1.41
PMCID: PMC3746044  PMID: 24010105
Meckel's diverticulum; Scintigraphy; Meckel's scan; Diagnosis; Child; Radionuclide imaging
19.  Cervical Pedicle Screw Insertion Using the Technique with Direct Exposure of the Pedicle by Laminoforaminotomy 
Objective
To present the accuracy and safety of cervical pedicle screw insertion using the technique with direct exposure of the pedicle by laminoforaminotomy.
Methods
We retrospectively reviewed 12 consecutive patients. A total of 104 subaxial cervical pedicle screws in 12 patients had been inserted. We also assessed the clinical and radiological outcomes and analyzed the direction and grade of pedicle perforation (grade 0: no perforation, 1: <25%, 2: 20% to 50%, 3: >50% of screw diameter) on the postoperative vascular-enhanced computed tomography scans. Grade 2 and 3 were considered as incorrect position.
Results
The correct position was found in 95 screws (91.3%); grade 0-75 screws, grade 1-20 screws and the incorrect position in 9 screws (8.7%); grade 2-6 screws, grade 3-3 screws. There was no neurovascular complication related with cervical pedicle screw insertion.
Conclusion
This technique (technique with direct exposure of the pedicle by laminoforaminotomy) could be considered relatively safe and easy method to insert cervical pedicle screw.
doi:10.3340/jkns.2012.52.5.459
PMCID: PMC3539080  PMID: 23323166
Cervical pedicle screw; Laminoforaminotomy; Pedicle perforation
20.  A Surgical Option for Multilevel Anterior Lumbar Interbody Fusion with Ponte Osteotomy to Achieve Optimal Lumbar Lordosis and Sagittal Balance 
Objective
To document lumbar lordosis (LL) of the spine and its change during surgeries with the different height but the same angle setting of the anterior cage. Additionally, we attempted to determine if sufficient LL is achieved at different cage heights and to quantify the change in LL during multi-level anterior lumbar interbody fusion (ALIF).
Methods
The medical records and radiographs of 42 patients who underwent more than 2 level ALIFs between 2008 and 2009 were retrospectively reviewed. We evaluated 3 parameters seen on lateral whole spine radiographs : LL, pelvic incidence (PI), and sagittal vertical axis (SVA). The mean follow-up time was 28.1 months and the final follow-up radiographs of all patients were reviewed at least 2 years after surgery. Statistical analysis was performed using the paired t-tests.
Results
Lumbar lordosis had changed up to 30 degrees immediately and 2 years after surgery (preoperative mean LL, SVA : 22.45 degrees, 112.31 mm; immediate postoperative mean LL, SVA : 54.45 degrees, 37.36 mm; final follow-up mean LL, SVA : 49.56 degrees, 26.95 mm). Our goal of LL is to obtain as much PI as possible, preoperative mean PI value was 55.38±3.35. The pre-operative and two year post-surgery follow-up mean of the Japanese Orthopedic Association score were 9.2±0.6 and 13.2±0.6 (favorable outcome rate : 95%), respectively. In addition, we were able to obtain good clinical outcomes and sagittal balance with a subsidence rate of 22.7%.
Conclusion
We were able to achieve sufficient LL, such that it was similar to the PI, utilizing multi-level ALIF with the use of a tall cage with the same angle setting of the cage. We have found out that achieving sufficient lumbar lordosis and sagittal balance require an anterior lumbar cage with high angle and height.
doi:10.3340/jkns.2012.52.4.365
PMCID: PMC3488646  PMID: 23133726
ALIF; Anterior interbody fusion; Multilevel ALIF; Pelvic incidence; Anterior lumbar cage; Sagittal balance
21.  Thyroid Cancer Initially Presenting Compression Fracture without Common Thyroid Symptoms 
Annals of Rehabilitation Medicine  2012;36(5):735-738.
Thyroid carcinoma is the commonest endocrinological malignancy. After papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC) is the second most common histological subtype. Common presentations of FTC include a solitary thyroid nodule and cervical lymphadenopathy. The incidence of individuals diagnosed with thyroid cancer showing initially distant metastatic disease ranges from 1 to 9%. Also, the incidence of solitary bone metastasis from thyroid is only 2 to 3%. We report a case of a patient with FTC whose initial presentation was low back pain and right buttock pain due to vertebral metastasis rather than the usual neck lumps or symptoms of thyroid disease.
doi:10.5535/arm.2012.36.5.735
PMCID: PMC3503953  PMID: 23185742
Follicular thyroid carcinoma; Spinal metastasis; Compression fracture
22.  Atypical Thoracic Solitary Plasmacytoma 
Annals of Rehabilitation Medicine  2012;36(5):739-743.
Plasmacytoma is a rare disease, which afflicts 2 to 3 people per every 100,000 of the general population. Solitary plasmacytoma accounts for 5% of the plasma cell neoplasm. Solitary plasmacytoma of the bone appears more vividly in the axial skeleton (25-60%), which has the red marrow and usually affects the thoracic vertebrae. We report a case of 54-year-old man who has a chest pain on the right side. After being treated for the muscle pain, his symptoms of pain were changed into weakness and allesthesia. We checked the MRI and found a mass lesion in the T5 vertebra, but there were no significant laboratory findings, in blood and urine samples. Finally, he got an operation due to the aggravation of the weakness. The result of biopsy indicated that it was a solitary plasmacytoma of the spine. After 5 months later, the weakness and allesthesia had disappeared.
doi:10.5535/arm.2012.36.5.739
PMCID: PMC3503954  PMID: 23185743
Atypical plasmacytoma; Solitary spinal tumor
23.  Acute Recurrent Pericarditis Accompanied by Graves' Disease 
Korean Circulation Journal  2012;42(6):419-422.
The etiology of acute pericarditis is often thought to be autoimmune, and Graves' disease has been reported in a few series to manifest as acute pericarditis. Since the etiology of recurrent pericarditis is known to be more associated with autoimmune causes, recurrent acute pericarditis may be a potential cardiovascular complication of Graves' disease. We report a case of recurrent acute pericarditis that was presumed to be associated with Graves' disease which was controlled after management of the problem of the thyroid.
doi:10.4070/kcj.2012.42.6.419
PMCID: PMC3390428  PMID: 22787473
Pericarditis; Graves disease
24.  Complete Genome Sequence of Multidrug-Resistant Acinetobacter baumannii Strain 1656-2, Which Forms Sturdy Biofilm 
Journal of Bacteriology  2011;193(22):6393-6394.
Acinetobacter baumannii is a Gram-negative bacterium causing nosocomial infections worldwide. To gain quick insight into the molecular basis of biofilm formation in A. baumannii, we determined the complete genome sequence of A. baumannii strain 1656-2, which forms sturdy biofilm and is resistant to multiple drugs.
doi:10.1128/JB.06109-11
PMCID: PMC3209198  PMID: 22038960
25.  A Case of Hypereosinophilic Syndrome Presenting With Multiorgan Infarctions Associated With Disseminated Intravascular Coagulation 
Thromboembolism is one of the most critical complications of hypereosinophilic syndrome (HES). We report here a case of multi-organ infarctions related to HES. A 23-year-old woman was referred to our hospital with hemoptysis. Not only pulmonary, but also renal and splenic infarctions were detected on computed tomography images. Blood tests showed profound peripheral eosinophilia. She was diagnosed with HES with disseminated intravascular coagulation (DIC). We initiated infusion of corticosteroids, which effectively suppressed peripheral eosinophilia. However, consumptive coagulopathy did not improve and intracerebral hemorrhage related to thrombosis then developed. Addition of interferon-alpha resulted in the correction of the DIC associated with HES.
doi:10.4168/aair.2012.4.3.161
PMCID: PMC3328734  PMID: 22548210
Hypereosinophilic syndrome; eosinophilia; thromboembolism; disseminated intravascular coagulation; consumptive coagulopathy; interferon-alpha

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