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1.  The EC50 of remifentanil to minimize the cardiovascular changes during head holder pinning in neurosurgery 
Korean Journal of Anesthesiology  2012;63(4):327-333.
Background
During neuroanesthesia, head holder pinning commonly results in sympathetic stimulation manifested by hemodynamic changes, such as increased heart rate and arterial blood pressure. Remifentanil has been used successfully to control acute autonomic responses during neurosurgical procedures. The objective of this study was to determine effect-site concentration of remifentanil for suppressing the hemodynamic response to head holder pinning with the probability of 50% (EC50).
Methods
Forty-one ASA physical status I or II patients, between the ages of 20-70, who were scheduled for neurosurgery were recruited into this study. After arrival in the operating room, standard monitoring was applied throughout the study, which included a bispectral index monitor. Both propofol and remifentanil were administered by Target-control infusion device. The Dixon "up-and-down" sequential allocation method was used to determine the EC50 of remifentanil.
Results
The EC50 of remifentanil was 2.19 ± 0.76 ng/ml by the turning point estimate (TPE). In probit analysis, EC50 was 2.42 ng/ml (95% CI : -0.62-4.66) and EC95 was 5.70 ng/ml (95% CI : 4.02-67.53). The EC50 estimator comes from isotonic regression is 2.90 ng/ml (95% CI : 1.78-3.65). The EC95 estimator comes from isotonic regression is 4.28 ng/ml (95% CI : 3.85-4.41).
Conclusions
This study showed that EC50 of remifentanil was 2.19 ± 0.76 ng/ml by TPE. EC50 was 2.42 ng/ml (95% CI -0.62-4.66) in probit analysis, as back up analysis. The EC50 estimator comes from isotonic regression is 2.90 ng/ml (95% CI : 1.78-3.65).
doi:10.4097/kjae.2012.63.4.327
PMCID: PMC3483491  PMID: 23115685
Hemodynamics; Neurosurgery; Propofol; Remifentanil
2.  Prediction of Chronicity of Anterior Cruciate Ligament Tear Using MRI Findings 
Clinics in Orthopedic Surgery  2013;5(1):19-25.
Background
The estimation of anterior cruciate ligament (ACL) tear is required in certain cases involving legal and financial administration, such as the worker's compensation and/or insurance. The aim of this study is to propose and evaluate a quantitative evaluation instrument to estimate the chronicity of the ACL tear, based on the four magnetic resonance imaging (MRI) findings.
Methods
One hundred and fifty one cases of complete ACL tear confirmed by arthroscopy were divided into 4 groups according to the time from ACL injury to MRI acquisition: acute (< 6 weeks), subacute (6 weeks to 3 months), intermediate (3 months to 1 year), and chronic (> 1 year). The four MRI findings including ACL morphology, joint effusion, posterior cruciate ligament angle, and bone bruise were analyzed for temporal changes among the 4 groups. Binary logistic regression equations were formulated using the MRI findings to estimate the chronicity of ACL tear in a quantitative manner, and the accuracy of the formulated regression equations was evaluated.
Results
The four MRI findings showed substantial temporal correlation with the time-limits of ACL injury to be included in the estimation model. Three predictive binary logistic equations estimated the probability of the ACL injury for the three cutoff time-limits of 6 weeks, 3 months, and 1 year with accuracies of 82.1%, 89.4%, and 89.4%, respectively.
Conclusions
A series of predictive logistic equations were formulated to estimate the chronicity of ACL tear using 4 MRI findings with chronological significance.
doi:10.4055/cios.2013.5.1.19
PMCID: PMC3582867  PMID: 23467216
Anterior cruciate ligament; Chronicity; Magnetic resonance imaging; Predictive model
3.  Eruptive Penile Syringomas Spreading to the Pubic Area and Lower Abdomen 
Annals of Dermatology  2013;25(1):116-118.
doi:10.5021/ad.2013.25.1.116
PMCID: PMC3582913  PMID: 23463834
4.  Relation of Absolute or Relative Adiposity to Insulin Resistance, Retinol Binding Protein-4, Leptin, and Adiponectin in Type 2 Diabetes 
Diabetes & Metabolism Journal  2012;36(6):415-421.
Background
Central fat mass (CFM) correlates with insulin resistance and increases the risk of type 2 diabetes and cardiovascular complications; however, peripheral fat mass (PFM) is associated with insulin sensitivity. The aim of this study was to investigate the relation of absolute and relative regional adiposity to insulin resistance index and adipokines in type 2 diabetes.
Methods
Total of 83 overweighted-Korean women with type 2 diabetes were enrolled, and rate constants for plasma glucose disappearance (KITT) and serum adipokines, such as retinol binding protein-4 (RBP4), leptin, and adiponectin, were measured. Using dual X-ray absorptiometry, trunk fat mass (in kilograms) was defined as CFM, sum of fat mass on the lower extremities (in kilograms) as PFM, and sum of CFM and PFM as total fat mass (TFM). PFM/TFM ratio, CFM/TFM ratio, and PFM/CFM ratio were defined as relative adiposity.
Results
Median age was 55.9 years, mean body mass index 27.2 kg/m2, and mean HbA1c level 7.12±0.84%. KITT was positively associated with PMF/TFM ratio, PMF/CFM ratio, and negatively with CFM/TFM ratio, but was not associated with TFM, PFM, or CFM. RBP4 levels also had a significant relationship with PMF/TFM ratio and PMF/CFM ratio. Adiponectin, leptin, and apolipoprotein A levels were related to absolute adiposity, while only adiponectin to relative adiposity. In correlation analysis, KITT in type 2 diabetes was positively related with HbA1c, fasting glucose, RBP4, and free fatty acid.
Conclusion
These results suggest that increased relative amount of peripheral fat mass may aggravate insulin resistance in type 2 diabetes.
doi:10.4093/dmj.2012.36.6.415
PMCID: PMC3530712  PMID: 23275935
Adiponectin; Adiposity; Insulin resistance; Leptin; Retinol binding protein-4
5.  The median effective effect-site concentration of remifentanil for minimizing the cardiovascular changes to endotracheal intubation during desflurane anesthesia in pediatric patients 
Korean Journal of Anesthesiology  2012;63(4):314-320.
Background
Desflurane has the most rapid onset and offset of action among the volatile anesthetic agents used for general anesthesia, but it can cause airway reactivity, tachycardia, and hypertension during induction, especially in pediatric patients. This study was designed to determine a median effective effect-site concentration (EC50) of remifentanil to prevent the cardiovascular changes due to tracheal intubation during the 1 minimum alveolar concentration (MAC) desflurane inhalation, which was required to prevent movement in response to a noxious stimulus in 50% of subjects, in pediatric patients.
Methods
Twenty-four pediatric patients between the ages 5-15 years were enrolled in this study. We injected thiopental intravenously, at the same time remifentanil was infused by Target Controlled Infusion (TCI) device. When the target effect-site concentration (Ce) of remifentanil reached a preset level, desflurane was administrated through the facial mask. Then, we assessed the signs of desflurane related airway reactivity and cardiovascular changes for 2 min. The up-and-down criteria was a 20% change in systolic blood pressure (SBP) and a heart rate (HR) between just prior to intubation and 1 min after intubation. The EC50 of remifentanil was calculated from 8 independent pairs using Dixon's up-and-down method.
Results
We studied 24 pediatric patients in range of 1-5 ng/ml of the Ce of remifentanil. No patient showed airway reactivity during the study. The EC50 of remifentanil to suppress the hemodynamic changes after tracheal intubation during desflurane anesthesia was calculated as 3.4 ± 0.9 ng/ml.
Conclusions
In pediatric anesthesia, the EC50 of remifentanil to minimize the cardiovascular changes due to tracheal intubation during 1 MAC desflurane anesthesia was 3.4 ± 0.9 ng/ml.
doi:10.4097/kjae.2012.63.4.314
PMCID: PMC3483489  PMID: 23115683
Child; Desflurane; Endotracheal intubation; Heart rate; Remifentanil; Systolic pressure
6.  Clinical significance of standardized uptake value and maximum tumor diameter in patients with primary extranodal diffuse large B cell lymphoma 
The Korean Journal of Hematology  2012;47(3):207-212.
Background
Maximum standardized uptake value (SUVmax) and maximum tumor diameter (MTD) have been shown to reflect survival outcome in diffuse large B cell lymphoma (DLBCL). However, applying these values to primary extranodal DLBCL is difficult because they are separate nosological entities with differences in genetic origin. We therefore decided to evaluate whether SUVmax and MTD on 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (18-FDG) positron emission tomography (PET) would affect the survival outcome in primary extranodal DLBCL.
Methods
From October 2005 to November 2010, 76 primary extranodal DLBCL patients receiving R-CHOP therapy were analyzed. All patients had undergone an initial 18-FDG PET/CT and conventional computed tomography (CT) of the neck, chest, abdomen, and pelvis for staging. Median follow-up period was 35 months.
Results
The SUVmax and MTD cut-off values were 11.0 and 7.5 cm, respectively. SUVmax≥11.0 predicted a short progression free survival (PFS, P=0.002) and overall survival (OS, P=0.002). MTD≥7.5 cm was associated with poor PFS (P=0.003) and OS (P=0.003). High International Prognostic Index (IPI) was also associated with the survival outcome (PFS, P=0.046; OS, P=0.030). Multivariate analysis revealed that SUVmax≥11.0 (PFS, hazard ratio [HR]=10.813, P=0.024; OS, HR=6.312, P=0.015); MTD≥7.5 cm (PFS, HR=5.631, P=0.008; OS, HR=4.072, P=0.008); and high IPI (PFS, P=0.027; OS, P=0.046) were independent prognostic factors.
Conclusion
It appears that both MTD and SUVmax can be independent prognostic factors in primary extranodal DLBCL.
doi:10.5045/kjh.2012.47.3.207
PMCID: PMC3464338  PMID: 23071476
Lymphoma; Large B-cell; Extranodal
7.  Evaluation of an Experimentally Designed Stereotactic Guidance System for Determining Needle Entry Point during Uniplanar Fluoroscopy-guided Intervention 
The Korean Journal of Pain  2012;25(2):81-88.
Background
In discography performed during percutaneous endoscopic lumbar discectomy (PELD) via the posterolateral approach, it is difficult to create a fluoroscopic tunnel view because a long needle is required for discography and the guide-wire used for consecutive PELD interrupts rotation of fluoroscope. A stereotactic system was designed to facilitate the determination of the needle entry point, and the feasibility of this system was evaluated during interventional spine procedures.
Methods
A newly designed stereotactic guidance system underwent a field test application for PELD. Sixty patients who underwent single-level PELD at L4-L5 were randomly divided into conventional or stereotactic groups. PELD was performed via the posterolateral approach using the entry point on the skin determined by premeasured distance from the midline and angles according to preoperative magnetic resonance imaging (MRI) findings. Needle entry accuracy provided by the two groups was determined by comparing the distance and angle measured by postoperative computed tomography with those measured by preoperative MRI. The duration and radiation exposure for determining the entry point were measured in the groups.
Results
The new stereotactic guidance system and the conventional method provided similarly accurate entry points for discography and consecutive PELD. However, the new stereotactic guidance system lowered the duration and radiation exposure for determining the entry point.
Conclusions
The new stereotactic guidance system under fluoroscopy provided a reliable needle entry point for discography and consecutive PELD. Furthermore, it reduced the duration and radiation exposure associated with determining needle entry.
doi:10.3344/kjp.2012.25.2.81
PMCID: PMC3324745  PMID: 22514774
equipment design; fluoroscopy; needle; percutaneous discectomy; stereotactic technique
8.  The changes of mitochondrial cytochrome c and GABAergic neuron in neuropathic pain model 
Korean Journal of Anesthesiology  2012;62(4):365-370.
Background
Role of cytochrome c (Cyt c) is an apoptogenic agent under certain conditions. The mitochondrial permeability transition pore (MPTP) plays an important role in cell death since it opens, leading to mitochondrial swelling and release of Cyt c, which initiates apoptosis. By inhibiting the opening of MPTP, cyclosporine A (CSA) may contribute to maintaining mitochondrial homeostasis. We investigate the effects of the partial sciatic nerve injury (PSNI)-induced neuropathic pain model on mitochondrial Cyt c release and the effects of CSA on neuroprotection by mitochondrial stabilizing activity in PSNI rats.
Methods
Rats were assigned to two groups that received different operations (Group P; PSNI operation, Group S; sham operation). The changes of cyt c and GABAergic neuron were evaluated in the spinal cord tissue. After which, PSNI rats randomly received CSA (Group C) or saline (Group S), and the changes of mechanical thresholds with Cyt c and GABAergic neuron were checked.
Results
PSNI in rats increased the release of cytosolic Cyt c. However, GABAergic cells were not decreased in the spinal cord level on the ipsilateral side to the PSNI. The second experiment reveal a reduction in Cyt c release, using CSA in PSNI model. Rats receiving CSA were afforded the antiallodynia without decrease of GABAergic cell.
Conclusions
The Cyt c probably contributes to nerve dysfunction after PSNI. PSNI induced neuropathic pain was profoundly linked to mitochondrial stabilization. Thus, the potent neuroprotector, CSA, might produce antiallodynia through its capability to inhibit the opening of MPTP.
doi:10.4097/kjae.2012.62.4.365
PMCID: PMC3337384  PMID: 22558504
Allodynia; Cyclosporine A; Cytochrome c; Mitochondrial permeability transition pore; Neuropathic pain
9.  Severe airway obstruction in an infant with congenital tracheal stenosis and congenital heart disease -A case report- 
Korean Journal of Anesthesiology  2012;62(3):285-288.
Congenital tracheal stenosis (CTS), though rare, is important because the mortality and morbidity rates are high in infants. Especially, associated congenital heart disease (CHD) in these infants may compound the effects of airway pathology. A 3-week-old patient with long-segmental tracheal stenosis below an anomalous right-upper lobe (RUL) bronchus had undergone a total correction of double outlet right ventricle. On third postoperative day, hypercarbia developed, and severe airway obstruction and atelectasis were detected. An emergency slide tracheoplasty was performed under cardiopulmonary bypass (CPB). The patient recovered well after the surgery. Thus, special attention needs to be paid during the postoperative intensive care of patients with congenital tracheal anomalies. Early detection and prompt diagnosis of airway obstruction can help reduce the morbidity and mortality rates. Further, it is important to select the suitable treatment of CTS associated with CHD.
doi:10.4097/kjae.2012.62.3.285
PMCID: PMC3315662  PMID: 22474559
Airway obstruction; Congenital; Heart disease; Tracheal stenosis
10.  The Effects of Glyburide on Apoptosis and Endoplasmic Reticulum Stress in INS-1 Cells in a Glucolipotoxic Condition 
Diabetes & Metabolism Journal  2011;35(5):480-488.
Background
β-cell death due to endoplasmic reticulum (ER) stress has been regarded as an important pathogenic component of type 2 diabetes. The possibility has been suggested that sulfonylurea, currently being used as one of the main oral hypoglycemic agents of type 2 diabetes, increases ER stress, which could lead to sulfonylurea failure. The authors of the present study examined ER stress of β-cells in a glucolipotoxic condition using glyburide (GB) in an environment mimicking type 2 diabetes.
Methods
Apoptosis was induced by adding various concentrations of GB (0.001 to 200 µM) to a glucolipotoxic condition using 33 mM glucose, and the effects of varied concentrations of palmitate were evaluated via annexin V staining. The markers of ER stress and pro-apoptotic markers were assessed by Western blotting and semi-quantitative reverse transcription-polymerase chain reaction. Additionally, the anti-apoptotic markers were evaluated.
Results
Addition of any concentration of GB in 150 µM palmitate and 33 mM glucose did not increase apoptosis. The expression of phosphorylated eukaryotic initiation factor (eIF-2α) was increased and cleaved caspase 3 was decreased by adding GB to a glucolipotoxic condition. However, other ER stress-associated markers such as Bip-1, X-box binding protein-1, ATF-4 and C/EBP-homologous protein transcription factor and anti-apoptotic markers phosphor-p85 phosphatidylinositol 3-kinase and phosphorylation of Akt did not change significantly.
Conclusion
GB did not show further deleterious effects on the degree of apoptosis or ER stress of INS-1 cells in a glucolipotoxic condition. Increased phosphorylation of eIF-2α may attenuate ER stress for adaptation to increased ER protein load.
doi:10.4093/dmj.2011.35.5.480
PMCID: PMC3221023  PMID: 22111039
Apoptosis; Endoplasmic reticulum stress; Glyburide; Insulin-secreting cells
11.  The effects of sevoflurane and propofol anesthesia on cerebral oxygenation in gynecological laparoscopic surgery 
Korean Journal of Anesthesiology  2011;61(3):225-232.
Background
Both the Trendelenburg position and pneumoperitoneum with carbon dioxide have been reported to increase intracranial pressure (ICP) and to alter cerebral blood flow or cerebral blood volume. Also anesthetic agents have variable effects on cerebral hemodynamics and ICP. The present study was conducted to determine whether regional cerebral oxygen saturation (rSO2) values differ between propofol and sevoflurane anesthesia during laparoscopic surgery in the Trendelenburg position.
Methods
Thirty-two adult women undergoing gynecological laparoscopic surgery were divided into sevoflurane and propofol groups. rSO2 values were recorded at 10 min after induction in the neutral position (Tpre), 10 min after the pneumoperitoneum in the Trendelenburg position (Tpt) and 10 min after desufflation in the neutral position (Tpost). For analysis of rSO2, we did ANOVA and univariate two-way ANCOVA with covariates being mean arterial pressure and end tidal carbon dioxide tension.
Results
Between sevoflurane and propofol groups, the change in rSO2 was significantly different even after ANCOVA. rSO2 at Tpt (76.3 ± 5.9% in sevoflurane vs 69.4 ± 5.8% in propofol) and Tpost (69.5 ± 7.1% in sevoflurane vs 63.8 ± 6.6% in propofol) were significantly higher in the sevoflurane group compared with the propofol group. In the propofol group, rSO2 at Tpost was significantly lower than at Tpre (71.1 ± 4.8%) and cerebral oxygen desaturation occurred in two patients (14.3%).
Conclusions
Significantly lower rSO2 values were observed in the propofol group during gynecological laparoscopic surgery. The possibility of cerebral oxygen desaturation should not be overlooked during propofol anesthesia even after desufflation of the abdomen in the neutral position.
doi:10.4097/kjae.2011.61.3.225
PMCID: PMC3198184  PMID: 22025945
Cerebral hypoxia; Head-down tilt; Near-infrared spectroscopy; Pneumoperitoneum; Propofol; Sevoflurane
12.  Subcutaneous versus Intraarticular Indwelling Closed Suction Drainage after TKA: A Randomized Controlled Trial 
Background
TKA can involve substantial bleeding, and the issue regarding whether vacuum drainage should be used during TKA continues to be debated as both methods have disadvantages.
Questions/purposes
We therefore asked whether subcutaneous indwelling vacuum drainage is advantageous over intraarticular indwelling vacuum drainage in terms of blood drainage, bleeding-related complications, and functional outcomes in primary TKA.
Patients and methods
We randomized 111 patients undergoing TKAs to have either a subcutaneous indwelling or an intraarticular indwelling catheter and compared the two groups for blood loss (hemoglobin decrease, transfusion requirements, hypotension episode), incidence of wound problems (requirements for dressing reinforcement, oozing, hematoma, hemarthrosis, ecchymosis, infection), and functional outcomes (recovery of motion arc, American Knee Society, WOMAC, and SF-36 scores) at 12 months after surgery.
Results
The mean vacuum drainage volume was less in the subcutaneous indwelling group than in the intraarticular indwelling group (140 mL versus 352 mL). The groups were similar in terms of decreases in hemoglobin after 2 and 5 days (3.0 versus 3.3 g/dL and 3.3 versus 3.7 g/dL, respectively), allogenic transfusion requirements (4% versus 11%), incidence of wound problems, and functional scores.
Conclusions
The data suggest subcutaneous indwelling closed-suction drainage is a reasonable alternative to intraarticular indwelling closed-suction drainage and to no suction drainage.
Level of Evidence
Level I, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-010-1243-6
PMCID: PMC2895852  PMID: 20127212
13.  The proper effect site concentration of remifentanil for prevention of myoclonus after etomidate injection 
Korean Journal of Anesthesiology  2011;61(2):127-132.
Background
Etomidate frequently induces myoclonus when administered intravenously with bolus injection during anesthetic induction. This can be bothersome for the anesthesiologist. The dose of remifentanil appropriate for preventing myoclonus without side effects was investigated.
Methods
All patients with American Society of Anesthesiologists (ASA) physical status I-III were divided into three groups (n = 33 per group) according to the pretreatment effect site concentration of remifentanil (Ultiva, Glaxo-Wellcome, München, Germany) of 0, 2 or 4 ng/ml (Group N: 0 ng/ml, Group R: 2 ng/ml, Group Q: 4 ng/ml) by a target controlled infusion (TCI) system. After a 0.3 mg/kg dose of etomidate was injected intravenously for over 1 minute for anesthetic induction, myoclonus was observed. Before the etomidate injection, the patients were pretreated with remifentanil and their side effects were monitored.
Results
The number of patients showing myoclonus was significantly different among the groups. The incidence of myoclonus was 81%, 12% and 0% (groups N, R, and Q, respectively, P < 0.01). Side effects including bradycardia and hypotension did not occur in either Group R or Q. Chest wall rigidity occured in 45% of patients in Group Q.
Conclusions
Administration with a 2 ng/ml effect site concentration of remifentanil could reduce the incidence of myoclonus caused by etomidate bolus injection without chest wall rigidity.
doi:10.4097/kjae.2011.61.2.127
PMCID: PMC3167131  PMID: 21927682
Etomidate; Myoclonus; Remifentanil
14.  Gender Differences in the Correlation between Symptom and Radiographic Severity in Patients with Knee Osteoarthritis 
Background
The effects of gender on the relationship between symptom manifestations and radiographic grades of knee osteoarthritis are not well understood.
Questions/purposes
We therefore determined the increments of symptom progression with regard to radiographic grades of knee osteoarthritis and asked if those increments differed by gender and whether symptom severity was differentially manifested by gender within the same grade.
Methods
We recruited 660 community residents; 368 (56%) women and 292 (44%) men. The mean subject age was 71.5 years (range, 65–91 years). Severity of symptoms was measured using the WOMAC and SF-36 scales, and the radiographic severity using Kellgren–Lawrence grades. Incremental changes in WOMAC and SF-36 scores were compared between adjacent Kellgren–Lawrence grades separately in men and women, and in the overall population. We compared symptom severity between men and women with the same radiographic grade.
Results
For the entire cohort, the mean incremental change in symptom severity was not gradual between the adjacent radiographic grades but was greater between Kellgren–Lawrence Grades 1 and 2 and Grades 2 and 3 than between Grades 0 and 1 or Grades 3 and 4. The patterns of incremental changes in symptom severity differed between men and women: women had more severe symptom progression between Kellgren–Lawrence Grades 2 and 3 and Grades 3 and 4 than men. Furthermore, women had worse mean WOMAC and SF-36 scores than men with the same radiographic grade of knee osteoarthritis.
Conclusions
These data suggest symptom progression is not gradual between adjacent radiographic grades, and for the same radiographic grade, symptoms are worse in women.
Level of Evidence
Level III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-010-1282-z
PMCID: PMC2881984  PMID: 20204559
15.  Animal Models of Periventricular Leukomalacia 
Laboratory Animal Research  2011;27(2):77-84.
Periventricular leukomalacia, specifically characterized as white matter injury, in neonates is strongly associated with the damage of pre-myelinating oligodendrocytes. Clinical data suggest that hypoxia-ischemia during delivery and intrauterine or neonatal infection-inflammation are important factors in the etiology of periventricular leukomalacia including cerebral palsy, a serious case exhibiting neurobehavioral deficits of periventricular leukomalacia. In order to explore the pathophysiological mechanisms of white matter injury and to better understand how infectious agents may affect the vulnerability of the immature brain to injury, novel animal models have been developed using hypoperfusion, microbes or bacterial products (lipopolysaccharide) and excitotoxins. Such efforts have developed rat models that produce predominantly white matter lesions by adopting combined hypoxia-ischemia technique on postnatal days 1-7, in which unilateral or bilateral carotid arteries of animals are occluded (ischemia) followed by 1-2 hour exposure to 6-8% oxygen environment (hypoxia). Furthermore, low doses of lipopolysaccharide that by themselves have no adverse-effects in 7-day-old rats, dramatically increase brain injury to hypoxic-ischemic challenge, implying that inflammation sensitizes the immature central nervous system. Therefore, among numerous models of periventricular leukomalacia, combination of hypoxia-ischemia-lipopolysaccharide might be one of the most-acceptable rodent models to induce extensive white matter injury and ensuing neurobehavioral deficits for the evaluation of candidate therapeutics.
doi:10.5625/lar.2011.27.2.77
PMCID: PMC3145996  PMID: 21826166
Periventricular leukomalacia; white matter injury; cerebral palsy; hypoperfusion (hypoxia-ischemia); inflammation (lipopolysaccharide); premyelinating oligodendrocytes
16.  Different Antiulcer Activities of Pantoprazole in Stress, Alcohol and Pylorus Ligation-Induced Ulcer Models 
Laboratory Animal Research  2011;27(1):47-52.
Antiulcer effects of pantoprazole, a proton-pump inhibitor, on water-immersion restraint stress (WIRS)-, alcohol (ethanol)- and pylorus ligation-induced gastric ulcers were investigated in male rats. Rats were orally administered with pantoprazole 30 min prior to exposure to various types of ulcer inducers. In stress-induced ulcer model, rats were subjected to WIRS at 22℃ for 4 hours, and the degree of ulcer (in mm) was evaluated. In alcohol-induced ulcer model, rats were orally administered with pure (100%) ethanol (1 mL/kg), and the ulcer lesions were measured 1 hour after ethanol challenge. In pylorus ligation-induced ulcer model, rats were subjected to pylorus ligation, and the degree of erosions and ulcers was scored 17 hours after the operation. Pantoprazole attenuated the ulcer lesions induced by WIRS in a dose-dependent manner, exhibiting a median effective dose (ED50) value of 0.78 mg/kg. By comparison, pantoprazole was effective at relatively-high doses for the improvement of ethanol-induced ulcers, showing an ED50 value of 20.5 mg/kg. Notably, pantoprazole was practically ineffective (ED50>50.0) in pylorus ligation model. Taken together, it was confirmed that pantoprazole showed inhibitory activity on gastric ulcers induced by stress and alcohol, but was ineffective on pylorus ligation-induced ulcer. Therefore, the results indicate that proton-pump inhibitors including pantoprazole might reveal highly-different effects according to the type of ulcer inducers, and that the prescription of antiulcer agents should be carefully selected.
doi:10.5625/lar.2011.27.1.47
PMCID: PMC3145982  PMID: 21826160
Pantoprazole; gastric ulcer; stress; alcohol; pylorus ligation
17.  Increased Nephrotoxicity after Combined Administration of Melamine and Cyanuric Acid in Rats 
Laboratory Animal Research  2011;27(1):25-28.
Renal toxicity by melamine in combination with cyanuric acid (1:1) was investigated. Male rats were orally administered melamine plus cyanuric acid (5, 50 or 400 mg/kg each) for 3 days. In contrast to a negligible effect by melamine alone (50 mg/kg, a no-observed-adverse-effect-level: NOAEL), co-administration with cyanuric acid markedly increased the concentrations of blood urea nitrogen and creatinine, as well as kidney weight. A high dose (400 mg/kg) of melamine plus cyanuric acid induced more severe kidney toxicity. The increased blood parameters for kidney toxicity and organ weight lasted longer than 4 days. Combined treatment with melamine and cyanuric acid (50-400 mg/kg each) resulted in many gold-brown crystals and toxic lesions in renal tubules, which were not observed in animals treated with melamine alone (50 mg/kg). These results indicate that only a 3-day exposure to melamine in combination with cyanuric acid causes severe renal damage, even at a NOAEL for melamine found in a 13-week toxicity study. Therefore, it is suggested that the tolerable daily intake or regulatory/management levels of melamine need to be re-considered for cases of co-exposure with cyanuric acid.
doi:10.5625/lar.2011.27.1.25
PMCID: PMC3145992  PMID: 21826156
Melamine; cyanuric acid; nephrotoxicity; renal crystal
18.  Adiponectin is a potential catabolic mediator in osteoarthritis cartilage 
Arthritis Research & Therapy  2010;12(6):R231.
Introduction
Adiponectin has been implicated in the pathogenesis of osteoarthritis (OA). We studied the effects of adiponectin on the OA cartilage homeostasis.
Methods
Immunohistochemical analysis was performed to evaluate differential expression of adiponectin receptors (AdipoRs) in nonlesional and lesional areas of OA cartilage. Cartilage and chondrocytes from the knee joints of primary OA patients were cultured in the presence of adiponectin (0~30 μg/ml). The levels of total nitric oxide (NO), matrix metalloproteinase (MMP)-1, -3, and -13, and tissue inhibitor of metalloproteinase (TIMP)-1 were measured in the conditioned media. The levels of inducible NO synthase (iNOS) and MMPs were determined with the quantitative real-time reverse transcription-polymerase chain reaction. The concentrations of collagenase-cleaved type II collagen neoepitope (C1-2C) were determined in the supernatant of adiponectin-stimulated OA cartilage explants. The effects of kinase and NOS inhibitors were evaluated in the adiponectin-stimulated chondrocytes.
Results
The expression levels of both AdipoR1 and AdipoR2 were significantly higher in lesional than in nonlesional areas of OA cartilage. The increased rate of AdipoR1-positive chondrocytes was twice that of AdipoR2-positive chondrocytes when compared between nonlesional and lesional areas. Adiponectin-stimulated OA chondrocytes showed increased total NO and MMP-1, -3, and -13 levels compared with nonstimulated cells. The TIMP-1 level was not affected. The C1-2C levels were increased by adiponectin in OA cartilage explant culture. AMP-activated protein kinase (AMPK) and c-Jun N-terminal kinase (JNK) inhibitors (compound C and SP600125) significantly suppressed adiponectin-induced production of total NO and MMP-1, -3, and -13. Inducible NOS inhibitors enhanced the expression of the adiponectin-induced MMPs.
Conclusions
Adiponectin causes matrix degradation in OA cartilage and increases MMPs and iNOS expression via the AMPK and JNK pathways in human OA chondrocytes. The catabolic effects of adiponectin may be counteracted by NO.
doi:10.1186/ar3218
PMCID: PMC3046544  PMID: 21194467
19.  Intradural Extramedullary Tuberculoma Mimicking En Plaque Meningioma 
Clinics in Orthopedic Surgery  2010;2(4):260-263.
A 24-year-old man with tuberculosis meningitis developed acute paraplegia and sensory disturbances 5 weeks after receiving conventional antituberculous therapy. Magnetic resonance imaging revealed an intradural extramedullary long segmental mass mimicking en plaque meningioma at the T2-T6 vertebrae levels. Prompt surgical decompression was performed. A histology examination of the mass revealed a tuberculoma. After surgery, the patient showed improved motor power and a normal bladder function. Intradural extramedullary tuberculoma of the spinal cord is rare complication of tuberculosis meningitis, which can occur as a response to conventional antituberculous therapy.
doi:10.4055/cios.2010.2.4.260
PMCID: PMC2981785  PMID: 21119945
Tuberculoma; Spinal cord; En plaque meningioma
20.  Improved Early Clinical Outcomes of RP/PS Mobile-Bearing Total Knee Arthroplasties 
The rotating-platform posterior-stabilized (RP/PS) prosthesis was developed to take advantage of the benefits of the traditional RP mobile-bearing system and the posterior-stabilized design. This nonconsecutive cohort study compared the clinical outcomes of TKAs performed using a RP/PS mobile system or a floating-platform (FP) system. The clinical outcomes of 93 TKAs with a RP/PS prosthesis were compared with the same number of TKAs with a FP mobile-bearing prosthesis at 6, 12, and 24 months after surgery. Clinical outcomes differed between the FP and RP/PS groups as a function of length of followup. In the FP group, most outcomes peaked at 12 months and then deteriorated, whereas in the RP/PS group, outcomes stabilized or continued to improve between 12 and 24 months. The RP/PS group had greater maximum flexion throughout followup and better clinical outcomes 24 months after surgery. Patient satisfaction was superior in the RP/RS group. This study suggests the RP/PS prosthesis provides better functional outcomes, including greater maximum flexion and better patient satisfaction. We propose the RP/PS mobile-bearing system is a more attractive option than the FP mobile-bearing system for patient populations of elderly women similar to patients enrolled in our study.
Level of Evidence: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-009-0787-9
PMCID: PMC2758967  PMID: 19296186
21.  Bone Mineral Density in Prediabetic Men 
Korean Diabetes Journal  2010;34(5):294-302.
Background
There are many studies regarding the effects of insulin on bone metabolism and changes in bone mineral density (BMD) in the setting of diabetes. The effect of prediabetes on BMD is not known.
Methods
A total of 802 men participated in the Korea Rural Genomic Cohort Study (in Geumsan County). According to the results of an oral glucose tolerance test, subjects were classified into normal, prediabetic, and diabetic categories. One hundred twenty-four subjects diagnosed with type 2 diabetes were excluded, leaving 678 subjects for the study inclusion. BMD was estimated with a quantitative ultrasonometer.
Results
The average BMD T scores of normal and prediabetic subjects were -1.34 ± 1.42 and -1.33 ± 1.30, respectively; there was no significant difference in the BMD T scores between these groups. The BMD T score was inversely associated with age and positively correlated with body weight, body mass index, total cholesterol, low density lipoprotein cholesterol, and HbA1c. On multiple linear regression analysis, low density lipoprotein cholesterol was the only statistically significant variable for prediabetes (β = 0.007, P = 0.005). On the stepwise regression analysis, age (β = -0.026, P < 0.001), the body mass index (β = 0.079, P < 0.001), and low density lipoprotein cholesterol (β = 0.004, P = 0.016) were significant variables for prediabetes.
Conclusions
There was no significant difference in the BMD T score between the normal and prediabetic subjects. Further studies are needed regarding the association of fracture risk and changes in BMD with the development of overt diabetes.
doi:10.4093/kdj.2010.34.5.294
PMCID: PMC2972489  PMID: 21076577
Bone density; Insulin; Prediabetic state
22.  Differences between Sagittal Femoral Mechanical and Distal Reference Axes Should Be Considered in Navigated TKA 
In computer-assisted TKA, surgeons determine positioning of the femoral component in the sagittal plane based on the sagittal mechanical axis identified by the navigation system. We hypothesized mechanical and distal femoral axes may differ on lateral views and these variations are influenced by anteroposterior bowing and length of the femur. We measured angles between the mechanical axis and distal femoral axis on 200 true lateral radiographs of the whole femur from 100 adults. We used multivariate linear regression to identify predictors of differences between the axes. Depending on the method used to define the two axes, the mean angular difference between the axes was as much as 3.8° and as little as 0.0°, with standard differences ranging from 1.7° to 1.9°. Variation between the two axes increased with increased femoral bowing and increased femoral length. Surgeons should consider differences between the mechanical axes and distal femoral axes when they set the sagittal plane position of a femoral component in navigated cases. Our findings also may be relevant when measuring rotation of the femoral component in the sagittal plane from postoperative radiographs or when interpreting femoral component sagittal rotation results reported in other studies.
Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-009-0762-5
PMCID: PMC2866923  PMID: 19242764
23.  Comparison of Ultrasonography- and Fluoroscopy-Guided Facet Joint Block in the Lumbar Spine 
Asian Spine Journal  2010;4(1):15-22.
Study Design
Retrospective study.
Purpose
Facet joint block is performed for diagnostic or therapeutic purposes and generally carried out under computerd tomography (CT) or radiologic fluoroscopy guidance. Ultrasonography-guided facet block has recently been attempted. So, we compared the results of ultrasonography-guided facet joint block with the results of fluoroscopy-guided facet joint block.
Overview of Literature
Because fluoroscopic or CT guided facet joint block has been reported side effects, we performed spinal facet block using a fluoroscopy-guided method.
Methods
We selected 133 patients who had lumbar pain or referred pain. They were diagnosed as having spinal stenosis and hospitalized from January 2008 to June 2008. As the subjects, we selected 105 patients who had been follow-up for more than 6 months and carried out a prospective study.
Twenty six subjects were male and 25 were female in the fluoroscopy group (group 1) and their mean age was 56.1 years (range, 45 to 79 years). Twenty one were male and 33 were female in the ultrasonography-guided group (group 2). Their mean age was 58.3 years (range, 47 to 83 years). We studied the average time of the procedures, complications, the difference of the therapeutic cost between the two groups. We also evaluated the visual analogue scale (VAS) score and the Oswestry disability index.
Results
The procedure in group 2 averaged 4 minutes and 25 seconds, and in group 1, 4 minutes and 7 seconds. The coast was an average of 38,000 won in group 2 and 25,000 won in group 1. The VAS score was improved from an average of 7.5 (range, 5 to 9) to 2.8 (range, 2 to 6) in group 2 and from 7.8 (range, 4 to 10) to 2.7 (range, 2 to 5) in group 1. The Oswestry disability index was improved from an average of 32.3 (range, 28 to 41) to 23.5 (range, 17 to 26) in group 2 and from 34.2 (range, 29 to 43) to 24.8 (range, 18 to 28) in group 1. As for complications, worsening of lumbar pain, paresthesia, headache and allergic reaction were detected in 5 cases of group 2 and in 3 of group 1. Those symptoms were improved within several hours. One case of superficial infection that developed in group 2 was improved within several days.
Conclusions
We should consider that ultrasonography-guided facet joint block is a minimal invasive procedure that is easily carried out without radiation exposure.
doi:10.4184/asj.2010.4.1.15
PMCID: PMC2900164  PMID: 20622950
Lumbar pain; Ultrasonography; Facet joint block
24.  Clinical Implications of Anthropometric Patellar Dimensions for TKA in Asians 
Anthropometric patellar dimensions can influence implant design and surgical techniques in patellar resurfacing for TKA. We measured anthropometric patellar dimensions in 752 osteoarthritic knees (713 in females and 39 in males) treated with TKA in 466 Korean patients and compared them with reported dimensions for Western patients. We investigated the effects of postoperative overall thickness deviations, residual bony thickness after bone resection, and postoperative deviations of component center positions from median ridge positions versus clinical and radiographic outcomes evaluated 1 year after surgery. Korean patients undergoing TKA had thinner and smaller patellae than Western patients. We found no associations between preoperative to postoperative overall thickness differences and clinical and radiographic outcomes and no differences between knees with a residual bony thickness 12 mm or greater and knees with a residual thickness less than 12 mm, with the exception of WOMAC pain scores. We found no associations between postoperative deviations of component center position and clinical or radiographic outcomes. Our findings indicate bone resection for patellar resurfacing can be flexible without jeopardizing clinical outcome.
Level of Evidence: Level IV, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-008-0557-0
PMCID: PMC2650045  PMID: 18855087
25.  Ethanol extract of Angelica gigas inhibits croton oil-induced inflammation by suppressing the cyclooxygenase - prostaglandin pathway 
Journal of Veterinary Science  2010;11(1):43-50.
The anti-inflammatory effects of an ethanol extract of Angelica gigas (EAG) were investigated in vitro and in vivo using croton oil-induced inflammation models. Croton oil (20 µg/mL) up-regulated mRNA expression of cyclooxygenase (COX)-I and COX-II in the macrophage cell line, RAW 264.7, resulting in the release of high concentrations of prostaglandin E2 (PGE2). EAG (1~10 µg/mL) markedly suppressed croton oil-induced COX-II mRNA expression and PGE2 production. Application of croton oil (5% in acetone) to mouse ears caused severe local erythema, edema and vascular leakage, which were significantly attenuated by oral pre-treatment with EAG (50~500 mg/kg). Croton oil dramatically increased blood levels of interleukin (IL)-6 and PGE2 without affecting tumor-necrosis factor (TNF)-α and nitric oxide (NO) levels. EAG pre-treatment remarkably lowered IL-6 and PGE2, but did not alter TNF-α or NO concentrations. These results indicate that EAG attenuates inflammatory responses in part by blocking the COX-PGE2 pathway. Therefore, EAG could be a promising candidate for the treatment of inflammatory diseases.
doi:10.4142/jvs.2010.11.1.43
PMCID: PMC2833429  PMID: 20195064
Angelica gigas; croton oil; cyclooxygenase-II; inflammation; prostaglandin E2

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