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1.  Palatal Implants for Persistent Snoring and Mild Obstructive Sleep Apnea After Laser-Assisted Uvulopalatoplasty 
Laser-assisted uvulopalatoplasty (LAUP) was widely performed in 1990s as a surgical therapeutic procedure to improve snoring or mild obstructive sleep apnea (OSA). However, LAUP is not currently recommended as a treatment for OSA because the evidence for its efficacy is insufficient. Little is known about alternative minimally invasive surgery in patients who refuse continuous positive airway pressure or oral appliance after failed LAUP. We present a case of successful surgical treatment of persistent snoring and mild OSA with palatal implants after LAUP. This case suggests that palatal implants may be offered as an alternative surgical procedure for selective patients with persistent or recurrent snoring or mild OSA after LAUP.
PMCID: PMC3932353  PMID: 24587885
Obstructive sleep apnea; Snoring; Palate; Implants
2.  Effect of Isolated Uvulopalatopharyngoplasty on Subjective Obstructive Sleep Apnea Symptoms 
The aims of this study were 1) to evaluate the effect of isolated uvulopalatopharyngoplasty (UPPP) on subjective obstructive sleep apnea (OSA) symptoms in adult patients regardless of the response to surgery, and ultimately 2) to investigate the differences in changes in subjective OSA symptoms between successful and unsuccessful surgery groups.
Twenty consecutive adult patients who underwent isolated UPPP were enrolled. Pre- and postoperative subjective OSA symptoms (snoring, witnessed apnea, daytime sleepiness, morning headache, daytime fatigue, restless sleep, difficulty with morning arousal) and polysomnographic data were evaluated in all subjects. Changes in subjective OSA symptoms before and after surgery were investigated in the successful (n=11) and unsuccessful (n=9) groups. Surgical success was defined as a reduction of at least 50% in the preoperative apnea-hypopnea index (AHI) and a postoperative AHI less than 20 per hour.
After isolated UPPP, all subjective OSA symptoms changed significantly in the patients, especially in the successful group. In the unsuccessful group, snoring, witnessed apnea and daytime fatigue changed significantly, while other symptoms did not change significantly after surgery.
Isolated UPPP may improve subjective OSA symptoms in adult patients whom surgery was successful or unsuccessful. However, after isolated UPPP, the improvements in subjective OSA symptoms in the unsuccessful group may be different from those in the successful group.
PMCID: PMC3781229  PMID: 24069519
Adult; Obstructive sleep apnea; Polysomnography; Surgery; Symptom
3.  Cerebral Microbleeds: Their Associated Factors, Radiologic Findings, and Clinical Implications 
Journal of Stroke  2013;15(3):153-163.
Cerebral microbleeds (CMBs) are tiny, round dark-signal lesions that are most often detected on gradient-echo MR images. CMBs consist of extravasations of blood components through fragile microvascular walls characterized by lipohyalinosis and surrounding macrophages. The prevalence of CMBs in elderly subjects with no history of cerebrovascular disease is around 5%, but is much higher in patients with ischemic or hemorrhagic stroke. Development of CMBs is closely related to various vascular risk factors; in particular, lobar CMBs are thought to be associated with cerebral amyloid angiopathy. The presence of CMBs has been hypothesized to reflect cerebral-hemorrhage-prone status in patients with hypertension or amyloid microangiopathy. Stroke survivors with CMBs have been consistently found to have an elevated risk of subsequent hemorrhagic stroke or an antithrombotic-related hemorrhagic complication, although studies have failed to establish a link between CMBs and hemorrhagic transformation after thrombolytic treatment. A large prospective study is required to clarify the clinical significance of CMBs and their utility in a decision-making index.
PMCID: PMC3859003  PMID: 24396809
Cerebral microbleed; Ischemic stroke; Intracerebral hemorrhage; Antithrombotics; Gradient-echo MRI
4.  Spontaneous Carotid Cavernous Fistula in a Case with Protein S Deficiency that Newly Developed Ophthalmoplegia after Embolization 
Carotid cavernous fistula (CCF) is an abnormal communication between the carotid artery and the cavernous sinus. The pathogenesis of spontaneous CCF remains unclear, although sinus thrombosis is known to be a predisposing factor for dural arteriovenous fistula. Because spontaneous CCFs are mainly of the dural type, we considered that thrombogenic conditions, such as, protein S deficiency might be associated with CCF.
Case Report
A 42-year-old woman complained of conjunctival injection and retro-orbital pain that first appeared 1-month before visiting our hospital. She had no history of head trauma or intracranial surgery. Exophthalmos and chemosis were observed in her left eye, which also had lower visual acuity and higher intraocular pressure than the right eye. Magnetic resonance images and cerebral angiography revealed a left dural CCF. Her protein S was low, at 41% (normal range: 70-140%), but other hematologic values related to coagulation were normal. Her symptoms were relieved after initial transvenous coil embolization. However, a newly developed sixth-nerve palsy was detected 4 days after initial embolization. Follow-up angiography revealed a minimal shunt, and thus transvenous coil embolization was repeated. Two days later, the ophthalmoplegia started reducing, and 1-month later it had almost disappeared.
To the best of our knowledge, this is the first report of spontaneous dural CCF in a Korean patient with concurrent protein S deficiency. Interestingly, transient sixth-nerve palsy developed after transvenous coil embolization in this patient. This additional symptom caused by the residual fistula was relieved after additional transarterial embolization.
PMCID: PMC3212604  PMID: 22087212
carotid cavernous fistula; protein S deficiency; transvenous embolization; sixth-nerve palsy; complication
5.  Surgical Outcomes of Hemorrhagic Metastatic Brain Tumors 
Hemorrhagic metastatic brain tumors are not rare, but little is known about the surgical outcome following treatment. We conducted this study to determine the result of the surgical outcome of hemorrhagic metastatic brain tumors.
Materials and Methods
From July 2001 to December 2008, 21 patients underwent surgery for hemorrhagic metastatic brain tumors at our institution. 15 patients had lung cancer, 3 had hepatocellular carcinoma, and the rest had rectal cancer, renal cell carcinoma, and sarcoma. 20 patients had macroscopic hemorrhage in the tumors, and one patient had intracerebral hemorrhage surrounding the tumor. A retrospective clinical review was conducted focusing on the patterns of presenting symptoms and signs, as well as local recurrence following surgery.
Among 21 hemorrhagic brain metastases, local recurrence developed in two patients. The 12 month progression free survival rate was 86.1%. Mean time to progression was 20.8 months and median survival time after surgery was 11.7 months.
The results of our study showed that hemorrhagic metastatic brain tumors rarely recurred after surgery. Surgery should be considered as a good treatment option for hemorrhagic brain metastasis, especially in cases with increased intracranial pressure or severe neurologic deficits.
PMCID: PMC3138913  PMID: 21811426
Neoplasm metastasis; Brain; Hemorrhage; Local neoplasm recurrences; Surgery
6.  Role of hyaluronan in glioma invasion 
Cell Adhesion & Migration  2008;2(3):202-207.
Gliomas are the most common primary intracranial tumors. Their distinct ability to infiltrate into the extracellular matrix (ECM) of the brain makes it impossible to treat these tumors using surgery and radiation therapy. A number of different studies have suggested that hyaluronan (HA), the principal glycosaminoglycan (GAG) in the ECM of the brain, is the critical factor for glioma invasion. HA-induced glioma invasion was driven by two important molecular events: matrix metalloproteinase (MMP) secretion and upregulation of cell migration. MMP secretion was triggered by HA-induced focal adhesion kinase (FAK) activation, which transmits its signal through ERK activation and nuclear factor kappa B (NFκB) translocation. Another important molecular event is osteopontin (OPN) expression. OPN expression by AKT activation triggers cell migration. These results suggest that HA-induced glioma invasion is tightly regulated by signaling mechanisms, and a detailed understanding of this molecular mechanism will provide important clues for glioma treatment.
PMCID: PMC2634087  PMID: 19262113
hyaluronan; matrix metalloproteinase; osteopontin; emodin; invasion; glioma
7.  Silent Microbleeds and Hemorrhagic Conversion of an Embolic Infarction 
We report a patient with multiple simultaneous embolic infarctions with localized hemorrhagic conversion. A 75-year-old male patient had several silent microbleeds (SMBs) exclusively in the cerebral cortex, and underwent angioplasty and stenting for bilateral carotid stenosis. He subsequently experienced embolic infarctions in the cortex and the striatum: the cortical infarction, where an SMB had been present, showed hemorrhagic conversion, whereas the striatal infarction did not. This case suggests that SMBs are indicators of an underlying hemorrhage-prone state.
PMCID: PMC2686849  PMID: 19513282
Ischemic stroke; Stroke assessment; Microbleeds; Hemorrhage
8.  Development of the Korean Version of the Sleep Apnea Quality of Life Index 
Obstructive sleep apnea (OSA) is a disorder characterized by repetitive partial or complete occlusion of the upper airway during sleep that affects quality of life. The aim of this study was to develop the Korean version of the sleep apnea quality of life index (K-SAQLI) and apply it in Korean patients with OSA.
Ninety-three patients with OSA completed the K-SAQLI. Its construct validity and responsiveness were tested by comparing the baseline and change scores obtained in each domain (i.e., daily functioning, social interactions, emotional functioning, and symptoms) using the medical outcome survey-short form 36 (SF-36).
The Cronbach α coefficients of internal reliability exceeded 0.60 in all the domains (daily functioning, 0.89; social interactions, 0.88; emotional functioning, 0.92; symptoms, 0.67; and total, 0.94). The K-SAQLI had a high test-retest correlation coefficient of 0.73 in the 20 randomized selected patients. The construct validity was confirmed by significant correlations with SF-36 subscale scores.
The results of this study demonstrate that the K-SAQLI may be applicable for clinical purposes.
PMCID: PMC3932345  PMID: 24587877
Obstructive sleep apnea; Questionnaires; Quality of life; Medical outcome survey-short form 36; Calgary sleep apnea quality of life index
9.  Protective Role of Trimetazidine Against Neomycin-induced Hair Cell Damage in Zebrafish 
Trimetazidine (TMZ) is known to reduce the generation of oxygen-derived free radicals. The objective of the present study was to evaluate the effects of TMZ on neomycin-induced ototoxicity in transgenic zebrafish (Brn3C: EGFP).
Five-day, postfertilization zebrafish larvae were exposed to 125 µM neomycin and one of the following TMZ concentrations for 1 hour: 10 µM, 100 µM, 500 µM, 1,000 µM, 1,500 µM, or 2,000 µM. Hair cells within the neuromasts of the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1) lateral lines were analyzed using fluorescence microscopy and confocal microscopy (n=10). Hair cell survival was calculated as a percentage of hair cells in the control group that were not exposed to neomycin. Ultrastructural changes were evaluated using scanning electron microscopy.
TMZ protected against neomycin-induced hair cell loss in the neuromasts (TMZ 1,000 µM, 11.2±0.4 cells; 125 µM neomycin only, 4.2±0.5 cells; n=10; P<0.05) and decreased the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) reaction. In the ultrastructural analysis, structures of mitochondria and hair cells within the neuromasts were preserved in zebrafish exposed to 125 µM neomycin and 1,000 µM TMZ.
TMZ attenuated neomycin-induced hair cell loss in zebrafish. The results of this study suggest that neomycin induces apoptosis, and that apoptotic cell death can be prevented by treatment with tremetazidine.
PMCID: PMC3863670  PMID: 24353861
Trimetazidine; Neomycin; Ototoxicity; Zebrafish
11.  Paradoxical effect of obesity on hemorrhagic transformation after acute ischemic stroke 
BMC Neurology  2013;13:123.
Among the patients with established coronary artery diseases, obese patients tend to have a more favorable prognosis, which is called as obesity paradox. Interestingly, mildly obese patients who underwent coronary revascularization had a lower risk of bleeding. In this context, we have investigated the association between obesity and hemorrhagic transformation (HTf) after acute ischemic stroke.
A total of 365 patients with first-ever acute ischemic stroke were included in this study. Demographic, clinical and radiological information was collected and HTf was evaluated through follow-up T2*-weighted gradient-recalled echo MRI performed usually within 1 week after occurrence of stroke. Body mass index was calculated, and obesity was defined using the World Health Organization Western Pacific Regional Office criteria.
The HTf was identified in 59 patients (16.2%). As the severity of obesity increased, the occurrence of HTf decreased. Compared with the normal weight group and after controlling possible confounders including acute and previous treatment, stroke severity and subtype, the risk of HTf decreased significantly in the obese group (odds ratio, 0.39; 95% confidence interval, 0.17-0.87).
The better outcome for HTf seen in obese patients suggests the existence of a “bleeding-obesity paradox” in acute ischemic stroke.
PMCID: PMC3848776  PMID: 24053109
Obesity; Hemorrhagic transformation; Bleeding-obesity paradox; Ischemic stroke; Body mass index
12.  Ultrafast refractive index control of a terahertz graphene metamaterial 
Scientific Reports  2013;3:2135.
Modulation of the refractive index of materials is elementary, yet it is crucial for the manipulation of electromagnetic waves. Relying on the inherent properties of natural materials, it has been a long-standing challenge in device engineering to increase the index-modulation contrast. Here, we demonstrate a significant amount of ultrafast index modulation by optically exciting non-equilibrium Dirac fermions in the graphene layer integrated onto a high-index metamaterial. Furthermore, an extremely-large electrical modulation of refractive index up to Δn ~ −3.4 (at 0.69 THz) is achieved by electrical tuning of the density of the equilibrium Dirac fermion in the graphene metamaterial. This manifestation, otherwise remaining elusive in conventional semiconductor devices, fully exploits the characteristic ultrafast charge relaxation in graphene as well as the strong capacitive response of the metamaterial, both of which enable us to drastically increase the light-matter interaction of graphene and the corresponding index contrast in the graphene metamaterials.
PMCID: PMC3701168  PMID: 23823715
13.  Serum Uric Acid Levels and Cerebral Microbleeds in Patients with Acute Ischemic Stroke 
PLoS ONE  2013;8(1):e55210.
Unlike experimental studies indicating a neuroprotective property of uric acid, clinical studies have shown that elevated levels of uric acid are associated with a risk of ischemic stroke. However, the association of uric acid with cerebral hemorrhage has seldom been tested. We aimed to elucidate the association between uric acid and cerebral microbleeds (CMBs), a hemorrhage-prone cerebral microangiopathy. Seven hundred twenty-four patients with ischemic stroke who were consecutively admitted to our hospital were included in this study. We collected demographic, clinical, and laboratory data, including uric acid level, and examined the presence of CMBs using T2*-weighted gradient-echo MRI. We used logistic regression analysis to examine an independent association between uric acid and CMBs. Two-hundred twenty-six patients had CMBs (31.2%). After adjusting for possible confounders, elevated uric acid was independently associated with the presence of CMBs (the highest quartile vs. lowest quartile, adjusted odd ratio [OR], 1.98; 95% confidence interval [CI], 1.16–3.39). This association retained in patients with deep or infratentorial CMBs (with or without lobar CMBs) but not among those with lobar CMBs. In addition, this association was robust among patients with hypertension (the highest quartile vs. lowest quartile, adjusted OR, 2.74; 95% CI, 1.43–5.24). In contrast, we did not find the association in patients without hypertension. We demonstrated that serum uric acid is independently associated with the presence of CMBs. In particular, the relation between uric acid and CMBs was robust in hypertensive patients.
PMCID: PMC3555938  PMID: 23372838
14.  Non Small Cell Carcinoma Metastasis to Meningioma 
"Tumor-to-tumor" metastasis is a rare event; meningioma has been reported as the most common primary intracranial tumor to harbor cancer metastases. Several hypotheses have been previously proposed to explain this occurrence, but the exact mechanism by which these metastases develop into meningiomas is not yet understood. Magnetic resonance imaging and spectroscopy have been valuable diagnostic tools, but preoperative diagnosis of metastasis to meningioma remains highly difficult. We present a case report of a metastasis of non-small cell lung cancer into an intracranial meningioma.
PMCID: PMC3579081  PMID: 23441002
Metastasis; Meningioma; Lung cancer; Non-small cell; Tumor-to-tumor; Harbor cancer
15.  Impact of CHADS2 Score on Neurological Severity and Long-Term Outcome in Atrial Fibrillation-Related Ischemic Stroke 
Background and Purpose
The CHADS2 (an acronym for congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack or thromboembolism) score is a widely used system for estimating the risk of stroke in patients with atrial fibrillation. However, how the CHADS2 score is related to stroke severity and outcome in patients with strokes due to atrial fibrillation has not yet been elucidated.
We enrolled patients with atrial fibrillation who visited our stroke center within 7 days after the onset of acute ischemic stroke between October 2002 and September 2008. CHADS2 scores were categorized into three groups: 0 points, low risk; 1 or 2 points, intermediate risk; and 3-6 points, high risk. Poor neurological state was defined as follows: a National Institutes of Health Stroke Scale (NIHSS) score of ≥2, and a modified Rankin Scale (mRS) score of ≥3 at discharge. Mortality information was ascertained as at December 2008.
A cohort of 298 patients with atrial-fibrillation-related stroke was included in this study. A high-risk CHADS2 score at admission was a powerful predictor of poor neurological outcome [for NIHSS: odds ratio (OR), 4.17; 95% confidence interval (CI), 1.76-9.87; for mRS: OR, 2.97; 95% CI, 1.23-7.16] after controlling for all possible confounders. In addition, a high-risk CHADS2 score was an independent predictor of all causes of death during the follow-up [hazard ratio (HR), 3.01; 95% CI, 1.18-7.65] and vascular death (HR, 12.25; 95% CI, 1.50-99.90).
Although the CHADS2 score was originally designed to distinguish patients with a future risk of stroke, our study shows that it may also be used to predict poor neurological outcome after atrial-fibrillation-related stroke.
PMCID: PMC3540283  PMID: 23323132
atrial fibrillation; ischemic stroke; CHADS2 score; neurological severity; outcome
16.  A Quantitative Comparison of the Vertebral Artery and Transverse Foramen Using CT Angiography 
Background and Purpose
The vertebral artery (VA) is important for the development of the transverse foramen (TF). Most studies of these structures have focused on anatomical anomalies. Therefore, we investigated quantitatively the association between the relative sizes of the TF and VA.
We recruited a consecutive series of subjects who underwent CT angiography to estimate the relative sizes of the VA and TF in axial source images. Two neurologists independently reviewed the axial CT images of 208 patients who had no history of transient ischemic attack or stroke. Averaged areas of the VA and TF were defined by the sum of the areas at each level from C3 to C6, divided by 4. Correlation analyses were adjusted for age, sex, and vascular risk factors.
The mean age of the subjects was 53 years. The interobserver and intraobserver reliabilities of TF size were good. There was a linear relationship between the sizes of the VA and TF on each side (right side: r2=0.58, p<0.001; left side: r2=0.62, p<0.001). The area of the VA was significantly associated with that of the TF after adjusting for vascular risk factors.
The size of the VA is strongly and linearly correlated with the size of the TF. These findings suggest that measurement of the TF and VA with CT angiography is a reliable method for evaluating VA diseases, and may provide new insight into the differentiation between VA hypoplasia and atherosclerosis of the VA.
PMCID: PMC3540284  PMID: 23323133
vertebral artery; transverse foramen; CT angiography; hypoplasia
17.  Incidence and Risk Factors for Leptomeningeal Carcinomatosis in Breast Cancer Patients with Parenchymal Brain Metastases 
The objective of study is to evaluate the incidence of leptomeningeal carcinomatosis (LMC) in breast cancer patients with parenchymal brain metastases (PBM) and clinical risk factors for the development of LMC.
We retrospectively analyzed 27 patients who had undergone surgical resection (SR) and 156 patients with whole brain radiation therapy (WBRT) as an initial treatment for their PBM from breast cancer in our institution and compared the difference of incidence of LMC according to clinical factors. The diagnosis of LMC was made by cerebrospinal fluid cytology and/or magnetic resonance imaging.
A total of 27 patients (14%) in the study population developed LMC at a median of 6.0 months (range, 1.0-50). Ten of 27 patients (37%) developed LMC after SR, whereas 17 of 156 (11%) patients who received WBRT were diagnosed with LMC after the index procedure. The incidence of LMC was significantly higher in the SR group compared with the WBRT group and the hazard ratio was 2.95 (95% confidence interval; 1.33-6.54, p<0.01). Three additional factors were identified in the multivariable analysis : the younger age group (<40 years old), the progressing systemic disease showed significantly increased incidence of LMC, whereas the adjuvant chemotherapy reduce the incidence.
There is an increased risk of LMC after SR for PBM from breast cancer compared with WBRT. The young age (<40) and systemic burden of cancer in terms of progressing systemic disease without adjuvant chemotherapy could be additional risk factors for the development of LMC.
PMCID: PMC3483318  PMID: 23115660
Brain metastasis; Breast cancer; Leptomeningeal carcinomatosis; Surgery; Whole brain radiation therapy
18.  Differential Expression of Extracellular Matrix Proteins in Senescent and Young Human Fibroblasts: a Comparative Proteomics and Microarray Study 
Molecules and Cells  2011;32(1):99-106.
The extracellular matrix (ECM) provides an essential structural framework for cell attachment, proliferation, and differentiation, and undergoes progressive changes during senescence. To investigate changes in protein expression in the extracellular matrix between young and senescent fibroblasts, we compared proteomic data (LTQ-FT) with cDNA microarray results. The peptide counts from the proteomics analysis were used to evaluate the level of ECM protein expression by young cells and senescent cells, and ECM protein expression data were compared with the microarray data. After completing the comparative analysis, we grouped the genes into four categories. Class I included genes with increased expression levels in both analyses, while class IV contained genes with reduced expression in both analyses. Class II and Class III contained genes with an inconsistent expression pattern. Finally, we validated the comparative analysis results by examining the expression level of the specific gene from each category using Western blot analysis and semiquantitative RT-PCR. Our results demonstrate that comparative analysis can be used to identify differentially expressed genes.
PMCID: PMC3887658  PMID: 21573704
extracellular matrix; microarray; proteomics
19.  Branch Atheromatous Plaque: A Major Cause of Lacunar Infarction (High-Resolution MRI Study) 
Lacunar infarctions account for up to 25% of all ischemic strokes and, thus, constitute a numerically important subgroup. It is important that the two pathogeneses of lacunar infarction, that is, small-vessel occlusion and branch atheromatous disease, be differentiated because prognoses and treatment strategies differ. The authors evaluated the presence of branch atheromatous plaque in parent arteries that supply lacunar infarcts by high-resolution magnetic resonance imaging (HR-MRI).
HR-MRI was performed in 15 patients with (1) a clinical presentation consistent with classical lacunar syndromes; (2) an acute lacunar infarction by diffusion-weighted imaging, measuring ≤20 mm in maximal diameter; (3) a magnetic resonance angiography showing a normal middle cerebral artery or basilar artery supplying the ischemic lesion, and (4) no other obvious etiology for small-vessel distribution ischemic stroke.
The median time of vessel wall imaging after index events was 4 days (range, 2–15 days). Six of the 15 patients had a lacunar infarction in the middle cerebral artery territory, and 9 had a lesion in the basilar artery territory. HR-MRI detected underlying atheromatous plaques in 9 patients (60%) with a lacunar infarction. In these 9 patients, asymptomatic intracranial atherosclerotic stenosis was more frequent compared to patients without branch atheromatous plaque (55.6 vs. 16.7%). In pontine infarctions, ischemic lesions that extended to the pial base of the pons were more frequent in patients with branch atheromatous plaques (83.3 vs. 33.3%), and all the ischemic lesions and atheromatous plaques were on the same side (right, n = 2; left, n = 4). All plaques responsible for acute symptomatic lacunar infarction were enhanced in contrast-enhanced T1-weighted HR-MR images.
HR-MRI results enabled underlying symptomatic branch atheromatous disease to be detected in lacunar infarction patients. The experience gained during this study indicates that HR-MRI better delineates intracranial arterial lesions, suggesting that its use will lead to a further understanding of the mechanisms involved in stroke.
PMCID: PMC3468813  PMID: 23060895
High-resolution MRI; Lacunar infarction; Branch atheromatous disease
20.  A Prospective Population-based Study of Total Nasal Resistance in Korean Subjects 
Rhinomanometry is a widely accepted method for objective assessment of nasal patency. However, few studies have reported the values of otherwise healthy population for nasal resistance in East Asians. The purpose of this study was to measure normal total nasal resistance (TNR) values in a large sample of Korean adults and to reveal parameters contributing to TNR values.
Subjects were enrolled from a cohort of the Korean Genome and Epidemiology Study. They were evaluated by anthropometry, questionnaire, and active anterior rhinomanometry at transnasal pressures of 100 and 150 Pascal (Pa).
The study sample consisted of 2,538 healthy subjects (1,298 women and 1,240 men) aged 20 to 80 years. Normal reference TNR values were 0.19±0.08 Pa/cm3/second at 100 Pa and 0.22±0.09 Pa/cm3/second at 150 Pa. The TNR of women was significantly higher than that of men (P<0.0001). TNR decreased with increasing age in both genders (P<0.05). In women, lower body weight was related to increasing TNR. In men, current smokers had higher TNR than ex-smokers and never smokers.
The results of the present study provide information regarding the values of otherwise healthy population of TNR and parameters associated with TNR in Korean adults.
PMCID: PMC3314804  PMID: 22468201
Adult; Body weight; Nasal obstruction; Reference values; Rhinomanometry; Smoking
21.  Chemotherapy for Malignant Gliomas Based on Histoculture Drug Response Assay : A Pilot Study 
The Histoculture Drug Response Assay (HDRA), which measures chemosensitivity using minced tumor tissue on drug-soaked gelfoam, has been expected to overcome the limitations of in vitro chemosensitivity test in part. We analyzed interim results of HDRA in malignant gliomas to see if the test can deserve further clinical trials.
Thirty-three patients with malignant gliomas were operated and their tumor samples were examined for the chemosensitivity to 10 chosen drugs by HDRA. The most sensitive chemotherapy regimen among those pre-established was chosen based on the number of sensitive drugs or total inhibition rate (IR) of the regimen. The response was evaluated by 3 month magnetic resonance image.
Among 13 patients who underwent total resection of the tumor, 12 showed no evidence of disease and one patient revealed progression. The response rate in 20 patients with residual tumors was 55% (3 complete and 8 partial responses). HDRA sensitivity at the cut-off value of more than one sensitive drug in the applied regimen showed a sensitivity of 100%, specificity of 60% and predictability of 70%. Another cut-off value of >80% of total IR revealed a sensitivity of 100%, specificity of 69%, and predictability of 80%. For 12 newly diagnosed glioblastoma patients, median progression-free survival of the HDRA sensitive group was 21 months, while that of the non-sensitive group was 6 months (p=0.07).
HDRA for malignant glioma was inferred as a feasible method to predict the chemotherapy response. We are encouraged to launch phase 2 clinical trial with chemosensitivity on HDRA.
PMCID: PMC3259462  PMID: 22259689
Chemotherapy; Drug sensitivity tests; Malignant glioma
22.  Dynamic Temporal Change of Cerebral Microbleeds: Long-Term Follow-Up MRI Study 
PLoS ONE  2011;6(10):e25930.
Cerebral microbleeds (MBs) are understood as an important radiologic marker of intracerebral hemorrhage. We sought to investigate the temporal changes of MBs and clinical factors associated with the changes using long-term follow-up MRI.
Methods/Principal Findings
From October 2002 to July 2006, we prospectively enrolled patients with stroke or transient ischemic attack, and followed-up their brain MRIs with an interval >12 mo. We compared demographic factors, vascular risk factors, laboratory findings, and radiologic factors according to the presence or changes of MBs. A total of 224 patients successfully completed the follow-up examinations (mean, 27 months). Newly developed MBs were noted in 10 patients (6.8%) among those without MBs at baseline (n = 148), and in those with MBs at baseline (n = 76), the MB count had decreased in 11 patients (14.5%), and increased in 41 patients (53.9%). The estimated annual rate of change of MB numbers was 0.80 lesions per year in all patients, a value which became greater in those patients who exhibited MBs at baseline (MBs≥5, 5.43 lesions per year). Strokes due to small vessel occlusion and intracerebral hemorrhage, as well as white matter lesions were independently associated with an increased MB count, whereas the highest quartile of low-density lipoprotein (LDL) cholesterol was associated with a decreased MB count.
During the follow-up period, most of MBs showed dynamic temporal change. Symptomatic or asymptomatic small vessel diseases appear to act as risk factors while in contrast, a high level of LDL cholesterol may act as a protective factor against MB increase.
PMCID: PMC3191164  PMID: 22022473
23.  Involvement of mTOR signaling in sphingosylphosphorylcholine-induced hypopigmentation effects 
Sphingosylphosphorylcholine (SPC) acts as a potent lipid mediator and signaling molecule in various cell types. In the present study, we investigated the effects of SPC on melanogenesis and SPC-modulated signaling pathways related to melanin synthesis.
Melanin production was measured in Mel-Ab cells. A luciferase assay was used to detect transcriptional activity of the MITF promoter. Western blot analysis was performed to examine SPC-induced signaling pathways.
SPC produced significant hypopigmentation effects in a dose-dependent manner. It was found that SPC induced not only activation of Akt but also stimulation of mTOR, a downstream mediator of the Akt signaling pathway. Moreover, SPC decreased the levels of LC3 II, which is known to be regulated by mTOR. Treatment with the mTOR inhibitor rapamycin eliminated decreases in melanin and LC3 II levels by SPC. Furthermore, we found that the Akt inhibitor LY294002 restored SPC-mediated downregulation of LC3 II and inhibited the activation of mTOR by SPC.
Our data suggest that the mTOR signaling pathway is involved in SPC-modulated melanin synthesis.
PMCID: PMC3166904  PMID: 21838918
Akt/LC3 II/Melanocytes/mTOR/sphingosylphosphorylcholine
24.  Endoscopic Third Ventriculostomy in Patients with Shunt Malfunction 
This paper presents data from a retrospective study of endoscopic third ventriculostomy (ETV) in patients with shunt malfunction and proposes a simple and reasonable post-operative protocol that can detect ETV failure.
We enrolled 19 consecutive hydrocephalus patients (11 male and 8 female) who were treated with ETV between April 2001 and July 2010 after failure of previously placed shunts. We evaluated for correlations between the success rate of ETV and the following parameters : age at the time of surgery, etiology of hydrocephalus, number of shunt revisions, interval between the initial diagnosis of hydrocephalus or the last shunt placement and ETV, and the indwelling time of external ventricular drainage.
At the time of ETV after shunt failure, 14 of the 19 patients were in the pediatric age group and 5 were adults, with ages ranging from 14 months to 42 years (median age, 12 years). The patients had initially been diagnosed with hydrocephalus between the ages of 1 month 24 days and 32 years (median age, 6 years 3 months). The etiology of hydrocephalus was neoplasm in 7 patients; infection in 5; malformation, such as aqueductal stenosis or megacisterna magna in 3; trauma in 1; and unknown in 3. The overall success rate during the median follow-up duration of 1.4 years (9 days to 8.7 years) after secondary ETV was 68.4%. None of the possible contributing factors for successful ETV, including age (p=0.97) and the etiology of hydrocephalus (p=0.79), were statistically correlated with outcomes in our series.
The use of ETV in patients with shunt malfunction resulted in shunt independence in 68.4% of cases. Age, etiology of hydrocephalus, and other contributing factors were not statistically correlated with ETV success. External ventricular drainage management during the immediate post-ETV period is a good means of detecting ETV failure.
PMCID: PMC3098424  PMID: 21607179
Shunt failure; Secondary endoscopic third ventriculostomy; Hydrocephalus
25.  Acupuncture for sequelae of Bell's palsy: a randomized controlled trial protocol 
Trials  2011;12:71.
Incomplete recovery from facial palsy has a long-term impact on the quality of life, and medical options for the sequelae of Bell's palsy are limited. Invasive treatments and physiotherapy have been employed to relieve symptoms, but there is limited clinical evidence for their effectiveness. Acupuncture is widely used on Bell's palsy patients in East Asia, but there is insufficient evidence for its effectiveness on Bell's palsy sequelae. The objective is to evaluate the efficacy and safety of acupuncture in patients with sequelae of Bell's palsy.
This study consists of a randomized controlled trial with two parallel arms: an acupuncture group and a waitlist group. The acupuncture group will receive acupuncture treatment three times per week for a total of 24 sessions over 8 weeks. Participants in the waitlist group will not receive any acupuncture treatments during this 8 week period, but they will participate in the evaluations of symptoms at the start of the study, at 5 weeks and at 8 weeks after randomization, at which point the same treatment as the acupuncture group will be provided. The primary outcome will be analyzed by the change in the Facial Disability Index (FDI) from baseline to week eight. The secondary outcome measures will include FDI from baseline to week five, House-Brackmann Grade, lip mobility, and stiffness scales.
Trial registration
Current Controlled-Trials ISRCTN43104115; registration date: 06 July 2010; the date of the first patient's randomization: 04 August 2010
PMCID: PMC3062611  PMID: 21388554

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