Search tips
Search criteria

Results 1-13 (13)

Clipboard (0)

Select a Filter Below

Year of Publication
1.  At Least One Cyclic Teriparatide Administration Can Be Helpful to Delay Initial Onset of a New Osteoporotic Vertebral Compression Fracture 
Yonsei Medical Journal  2014;55(6):1576-1583.
Teriparatide markedly increases bone formation and strength, while reducing the incidence of new-onset osteoporotic vertebral compression fractures (OVCFs). In some countries, expenses for teriparatide use are covered by medical insurance for up to 6 months; however, the national medical insurance of the authors' country does not cover these expenses. This retrospective cohort study compared the therapeutic effects of teriparatide on the initial onset of a new OVCF after treatment of osteoporosis and/or related OVCFs with regard to therapeutic durations of longer than 3 months (LT3M) or shorter than 3 months (ST3M).
Materials and Methods
From May 2007 to February 2012, 404 patients who were prescribed and administered teriparatide and who could be followed-up for longer than 12 months were enrolled. They were divided into two groups depending on teriparatide duration: LT3M (n=132) and ST3M (n=272).
The group with the teriparatide duration of LT3M showed significantly less development of an initial OVCF within 1 year (p=0.004, chi-square). Duration of teriparatide use, body mass index, pre-teriparatide lowest spinal bone mineral density, and severity of osteoporosis significantly affected multiple regression analysis results (p<0.05). Survival analysis of first new-onset OVCFs demonstrated a significantly better survival rate for the LT3M group (log rank, p=0.005). Also, the ST3M group showed a higher odds ratio of 54.00 for development of an initial OVCF during follow-up than the LT3M group (Mantel-Haenzel common odds ratio, p=0.006).
At least one cyclic teriparatide administration is recommended to provide a protective effect against the initial onset of a new OVCF for up to one year after therapy.
PMCID: PMC4205697  PMID: 25323894
Osteoporosis; teriparatide; duration; vertebral compression fracture
2.  A Comparison of Assay Performance Between the Calcium Mobilization and the Dynamic Mass Redistribution Technologies for the Human Urotensin Receptor 
The popular screening method for urotensin (UT) receptor antagonists is to measure the intracellular calcium concentration with a calcium-sensitive fluorescent dye. This assay format has an inherent limitation on the problem related to the fluorescence interference as it involves fluorescent dyes. In the present study, a label-free assay for the screening of UT receptor antagonists was developed by using dynamic mass redistribution (DMR) assay based on label-free optical biosensor. The addition of urotensin II (UII) stimulated a DMR profile to HEK293 cells stably expressing the human UT receptor (HEK293UT cells) but not on parental cells. The EC50 value of UII in label-free assay was 4.58 nM, which is very similar to that in conventional calcium mobilization assay (4.15 nM). Compared with the calcium mobilization assay for UII (Z′ factor, 0.77), the current label-free assay presented improved Z′ factor (0.81), with a relatively similar S/B ratio (28.0 and 25.6, respectively). The known high-affinity UT receptor antagonists, SB657510, GSK562590, and urantide, exhibited comparable IC50 values but rather less potent in the DMR assay than in calcium mobilization. Our DMR assay was able to present various functional responses, including inverse agonism in SB657510 and GSK1562590 as well as partial agonism in urantide. Moreover, the DMR assay exerted the stable antagonist window upon the minimal agonist stimulus. These results suggest that the label-free cell-based UT receptor assay can be applicable to evaluate the various functional activities of UT receptor-related drug candidates.
PMCID: PMC4142844  PMID: 25147908
3.  Transpedicular curettage and drainage versus combined anterior and posterior surgery in infectious spondylodiscitis 
Indian Journal of Orthopaedics  2014;48(1):74-80.
Hematogeneous infectious spondylodiscitis usually occurs in older immunocompromised patients with other comorbidities. They are usually unable to undergo reconstructive anterior and posterior surgeries. Therefore, an alternative, less aggressive surgical method of transpedicular curettage and drainage was suggested. This study was designed to compare the surgical outcomes for the treatment of hematogeneous infectious spondylodiscitis between transpedicular curettage and drainage technique and conventional combined anterior and posterior surgery.
Materials and Methods:
Between January 2002 and July 2011, 26 patients underwent surgical treatment for hematogeneous infectious spondylodiscitis. The patients were classified into two groups depending on surgical modality: a transpedicular curettage and drainage (TCD) group and a combined anterior and posterior surgery (CAPS) group.
The TCD group consisted of 10 patients (mean age 68.0 years), and the CAPS group consisted of 16 patients (mean age 58.4 years). The mean postoperative followup periods were 36.9 (months) in the TCD group and 69.9 (months) in the CAPS group. The operation time was 180.6 ± 33.6 minutes in the TCD group and 332.7 ± 74.5 minutes in the CAPS group (P < 0.05). Postoperative independent ambulation began at postoperative 4.9 ± 2.4 days in the TCD group but at postoperative 15.1 ± 15.3 days in the CAPS group (P < 0.05). The postoperative hospital stays were 19.9 ± 7.8 days in the TCD group and 35.4 ± 33.3 days in the CAPS group (P < 0.05). The level of C-reactive proteins decreased significantly in both groups after surgery (P < 0.05).
Transpedicular curettage and drainage technique proved to be a useful technique for treating hematogeneous infectious spondylodiscitis in patients who were in poor heath with multiple comorbidities unable to undergo the conventional combined anterior and posterior surgery in a single day in terms of earlier ambulation, shorter hospitalization and similar clinical success rate.
PMCID: PMC3931157  PMID: 24600067
Curettage; drainage; infectious; spondylodiscitis; transpedicular
4.  Inhibitory Effect of an Urotensin II Receptor Antagonist on Proinflammatory Activation Induced by Urotensin II in Human Vascular Endothelial Cells 
Biomolecules & Therapeutics  2013;21(4):277-283.
In this study, we investigated the effects of a selective urotensin II (UII) receptor antagonist, SB-657510, on the inflammatory response induced by UII in human umbilical vein endothelial cells (EA.hy926) and human monocytes (U937). UII induced inflammatory activation of endothelial cells through expression of proinflammatory cytokines (IL-1β and IL-6), adhesion molecules (VCAM-1), and tissue factor (TF), which facilitates the adhesion of monocytes to EA.hy926 cells. Treatment with SB-657510 significantly inhibited UII-induced expression of IL-1β, IL-6, and VCAM-1 in EA.hy926 cells. Further, SB-657510 dramatically blocked the UII-induced increase in adhesion between U937 and EA.hy926 cells. In addition, SB-657510 remarkably reduced UII-induced expression of TF in EA.hy926 cells. Taken together, our results demonstrate that the UII antagonist SB-657510 decreases the progression of inflammation induced by UII in endothelial cells.
PMCID: PMC3819900  PMID: 24244812
Urotensin II; Urotensin II receptor antagonist; Adhesion molecules; Cytokines; Tissue factor; Endothelial cells
5.  External Validation of the Acute Physiology and Chronic Health Evaluation II in Korean Intensive Care Units 
Yonsei Medical Journal  2013;54(2):425-431.
This study was designed to validate the usefulness of the Acute Physiology and Chronic Health Evaluation (APACHE) II for predicting hospital mortality of critically ill Korean patients.
Materials and Methods
We analyzed data on 826 patients who had been admitted to nine intensive care units and were included in the Fever and Antipyretics in Critical Illness Evaluation study cohort.
Among the patients enrolled, 62% (512/826) were medical and 38% (314/826) were surgical patients. The median APACHE II score was 17 (11 to 23 interquartile range), and the hospital mortality rate was 19.5%. Age, underlying diseases, medical patients, mechanical ventilation, and renal replacement therapy were independently associated with hospital mortality. The calibration of APACHE II was poor (H=57.54, p<0.0001; C=55.99, p<0.0001), and the discrimination was modest [area under the receiver operating characteristic (aROC)=0.729]. Calibration was poor for both medical and surgical patients (H=63.56, p<0.0001; C=73.83, p<0.0001, and H=33.92, p<0.0001; C=33.34, p=0.0001, respectively), while discrimination was poor for medical patients (aROC=0.651) and modest for surgical patients (aROC=0.704). At the predicted risk of 50%, APACHE II had a sensitivity of 36.6% and a specificity of 87.4% for hospital mortality.
For Koreans, the APACHE II exhibits poor calibration and modest discrimination for hospital mortality. Therefore, a new model is needed to accurately predict mortality in critically ill Korean patients.
PMCID: PMC3575980  PMID: 23364977
APACHE II; calibration; discrimination; intensive care units; illness severity
7.  Transpedicular Curettage and Drainage of Infective Lumbar Spondylodiscitis: Technique and Clinical Results 
Clinics in Orthopedic Surgery  2012;4(3):200-208.
Infective spondylodiscitis usually occurs in patients of older age, immunocompromisation, co-morbidity, and individuals suffering from an overall poor general condition unable to undergo reconstructive anterior and posterior surgeries. Therefore, an alternative, less aggressive surgical method is needed for these select cases of infective spondylodiscitis. This retrospective clinical case series reports our novel surgical technique for the treatment of infective spondylodiscitis.
Between January 2005 and July 2011, among 48 patients who were diagnosed with pyogenic lumbar spondylodiscitis or tuberculosis lumbar spondylodiscitis, 10 patients (7 males and 3 females; 68 years and 48 to 78 years, respectively) underwent transpedicular curettage and drainage. The mean postoperative follow-up period was 29 months (range, 7 to 61 months). The pedicle screws were inserted to the adjacent healthy vertebrae in the usual manner. After insertion of pedicle screws, the drainage pedicle holes were made through pedicles of infected vertebra(e) in order to prevent possible seeding of infective emboli to the healthy vertebra, as the same instruments and utensils are used for both pedicle screws and the drainage holes. A minimum of 15,000 mL of sterilized normal saline was used for continuous irrigation through the pedicular pathways until the drained fluid looked clear.
All patients' symptoms and inflammatory markers significantly improved clinically between postoperative 2 weeks and postoperative 3 months, and they were satisfied with their clinical results. Radiologically, all patients reached the spontaneous fusion between infected vertebrae and 3 patients had the screw pulled-out but they were clinically tolerable.
We suggest that our method of transpedicular curettage and drainage is a useful technique in regards to the treatment of infectious spondylodiscitic patients, who could not tolerate conventional combined anterior and posterior surgery due to multiple co-morbidities, multiple level infectious lesions and poor general condition.
PMCID: PMC3425650  PMID: 22949951
Spondylodiscitis; Curettage; Drainage; Surgery; Transpedicular
8.  Osteoporotic profiles in elderly patients with symptomatic lumbar spinal canal stenosis 
Indian Journal of Orthopaedics  2012;46(3):279-284.
The osteoporosis and lumbar canal stenosis, in elderly patients are under diagnosed and under reported. We report a cross sectional study to demonstrate the osteoporotic profile in patients with lumbar spinal stenosis (LSS) and to determine the proportion of patients with LSS who need to be treated for osteoporosis.
Materials and Methods:
One hundred and six postmenopausal patients with symptomatic LSS were evaluated for osteoporotic profile, which included lumbar and hip bone mineral density (BMD), serum vitamin D concentration, bone resorption and formation markers. Demographic and disease related variables were analyzed to identify the association with the risk of osteoporosis or osteopenia. Statistical analysis used were multivariate logistic regression with a forward stepwise procedure.
Twenty-four patients (22.6%) had osteoporosis and 60 (56.6%) had osteopenia. Overall, 84 patients (79.2%) with symptomatic LSS had osteoporosis or osteopenia. Fifty-nine patients (55.6%) had hypovitaminosis D. All bone turnover makers [alkaline phosphatase, osteocalcin, urinary-N-terminal telopeptide (u-NTx)] were demonstrated to be within normal range. Only age was associated with the risk of osteoporosis or osteopenia in the hip region. In the lumbar spine, all variables were not associated with osteoporosis or osteopenia. 44 patients (41.5%) required treatment for osteoporosis as per risk factors for osteoporosis. According to the guidelines from the Health Insurance Review Agency, however, only 20 patients (18.8% required) qualified for reimbursement for osteoporosis medications.
LSS is associated with osteopenia, osteoporosis, and hypovitaminosis D, which should prompt careful screening and treatment in cases of osteoporosis and osteoarthritis.
PMCID: PMC3377137  PMID: 22719113
Bone mineral density; bone turnover marker; hypovitaminosis D; lumbar spinal stenosis; osteoporosis
9.  Prevalence of hip pathology in patients over age 50 with spinal conditions requiring surgery 
Indian Journal of Orthopaedics  2012;46(3):291-296.
The objective of this study was to evaluate of prevalence of co-existing spine and hip disease using initial screening kidney–ureter–bladder (KUB) radiograph in patients over 50 who underwent spinal surgery.
Materials and Methods:
The study subjects were 388 patients (male: female=117:271; mean age 62.0 years) who underwent spinal surgery between 2008 and 2010. We retrospectively reviewed the initial KUB radiographs used to diagnose the spine and hip disease. Depending on the extent of acetabular and hip joint visualization in KUB, we divided the subjects into three groups: Acetabulum, hip joint, and femoral neck visualization. The hip visualization rate was also assessed with respect to patient height. χ2 and logistic regression test were used for statistical analysis.
126 (32.5%) cases had significant hip pathology including hip osteoarthritis (Kellgren/Lawrence grade 3 in 123 cases, grade 4 in 3 cases) and avascular necrosis (1 case each of Ficat stage IIA and IIB), and 8 cases had other morphologic abnormalities. Regarding acetabulum–hip visualization in KUB, 7 (1.8%) cases had acetabulum visualization only, 16 (4.1%) had hip joint visualization, and 365 (94.1%) had femoral neck including lesser trochanter visualization. Patients were categorized into four groups according to height (less than 150 cm, 150–159 cm, 160–169 cm, greater than 170 cm). The hip visualization rates differed significantly among these four groups (P<0.05).
The prevalence of discernible hip pathology in patients who underwent spinal surgery was 32.5%. Hip joint visualization was excellent (98.2%) in KUB radiographs. Hence, spinal surgeons should pay attention to hip pathology in surgically indicated spinal patients.
PMCID: PMC3377139  PMID: 22719115
Hip pathology; spinal surgery; elderly
10.  Association of body temperature and antipyretic treatments with mortality of critically ill patients with and without sepsis: multi-centered prospective observational study 
Critical Care  2012;16(1):R33.
Fever is frequently observed in critically ill patients. An independent association of fever with increased mortality has been observed in non-neurological critically ill patients with mixed febrile etiology. The association of fever and antipyretics with mortality, however, may be different between infective and non-infective illness.
We designed a prospective observational study to investigate the independent association of fever and the use of antipyretic treatments with mortality in critically ill patients with and without sepsis. We included 1,425 consecutive adult critically ill patients (without neurological injury) requiring > 48 hours intensive care admitted in 25 ICUs. We recorded four-hourly body temperature and all antipyretic treatments until ICU discharge or 28 days after ICU admission, whichever occurred first. For septic and non-septic patients, we separately assessed the association of maximum body temperature during ICU stay (MAXICU) and the use of antipyretic treatments with 28-day mortality.
We recorded body temperature 63,441 times. Antipyretic treatment was given 4,863 times to 737 patients (51.7%). We found that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen independently increased 28-day mortality for septic patients (adjusted odds ratio: NSAIDs: 2.61, P = 0.028, acetaminophen: 2.05, P = 0.01), but not for non-septic patients (adjusted odds ratio: NSAIDs: 0.22, P = 0.15, acetaminophen: 0.58, P = 0.63). Application of physical cooling did not associate with mortality in either group. Relative to the reference range (MAXICU 36.5°C to 37.4°C), MAXICU ≥ 39.5°C increased risk of 28-day mortality in septic patients (adjusted odds ratio 8.14, P = 0.01), but not in non-septic patients (adjusted odds ratio 0.47, P = 0.11).
In non-septic patients, high fever (≥ 39.5°C) independently associated with mortality, without association of administration of NSAIDs or acetaminophen with mortality. In contrast, in septic patients, administration of NSAIDs or acetaminophen independently associated with 28-day mortality, without association of fever with mortality. These findings suggest that fever and antipyretics may have different biological or clinical or both implications for patients with and without sepsis.
Trial registration NCT00940654
PMCID: PMC3396278  PMID: 22373120
body temperature; antipyretic; fever; critical illness; mortality
11.  Airway fire injury during rigid bronchoscopy in a patient with a silicon stent -A case report- 
Korean Journal of Anesthesiology  2012;62(2):184-187.
Therapeutic bronchoscopy is widely employed as an effective first-line treatment for patients with central airway obstructions. Airway fires during rigid bronchoscopy are rare, but can have potentially devastating consequences. Pulmonologist and anesthesiologist undertaking this type of procedure should be aware of this serious problem and be familiar with measures to avoid this possibly fatal complication. We report the case of a 24-year-old patient with a silicone stent who experienced an electrocautery-induced airway fire during rigid bronchoscopy.
PMCID: PMC3284744  PMID: 22379577
Airway fire; Electrocautery; Rigid bronchoscopy; Silicone stent
12.  IKKβ inhibitor identification: a multi-filter driven novel scaffold 
BMC Bioinformatics  2010;11(Suppl 7):S15.
Nuclear factor kappa B (NF-κB) is a chief nuclear transcription factor that controls the transcription of various genes; and its activation is tightly controlled by Inhibitor kappa B kinase (IKK). The irregular transcription of NF-κB has been linked to auto-immune disorders, cancer and other diseases. The IKK complex is composed of three units, IKKα, IKKβ, and the regulatory domain NEMO, of which IKKβ is well understood in the canonical pathway. Therefore, the inhibition of IKKβ by drugs forms the molecular basis for anti-inflammatory drug research.
The ligand- and structure-based virtual screening (VS) technique has been applied to identify IKKβ inhibitors from the ChemDiv database with 0.7 million compounds. Initially, a 3D-QSAR pharmacophore model has been deployed to greatly reduce the database size. Subsequently, recursive partitioning (RP) and docking filters were used to screen the pharmacophore hits. Finally, 29 compounds were selected for IKKβ enzyme inhibition assay to identify a novel small molecule inhibitor of IKKβ protein.
In the present investigation, we have applied various computational models sequentially to virtually screen the ChemDiv database, and identified a small molecule that has an IC50 value of 20.3μM. This compound is novel among the known IKKβ inhibitors. Further optimization of the hit compound can reveal a more potent anti-inflammatory agent.
PMCID: PMC2957683  PMID: 21106122
13.  Involvement of GADD153 and cardiac ankyrin repeat protein in cardiac ischemia-reperfusion injury 
Experimental & Molecular Medicine  2009;41(4):243-252.
Oxidative stress is critical for causing cardiac injuries during ischemia-reperfusion (IR), yet the molecular mechanism for this remains unclear. In the present study, we observe that hypoxia and reoxygenation, a component of ischemia, effectively induces apoptosis in the cardiac myocytes from neonatal rats and it concomitantly leads to induction of GADD153, an apoptosis-related gene. Furthermore, IR injury of rat heart showed a GADD153 overexpression in the ischemic area where the TUNEL reaction was positive. A downregulation of cardiac ankyrin repeat protein (CARP) was also observed in this ischemic area. Promoter deletion and reporter analysis revealed that hypoxia transcriptionally activates a GADD153 promoter through the AP-1 element in neonatal cardiomyocytes. Ectopic overexpression of GADD153 resulted in the downregulation of CARP expression. Accordingly, the induction of GADD153 mRNA were followed by the CARP down-regulation in an in vivo rat coronary ischemia/reperfusion injury model. These results suggest that GADD153 over-expression and the resulting downregulation of CARP may have causative roles in apoptotic cell death during cardiac IR injury.
PMCID: PMC2679233  PMID: 19299913
ANKRD1 protein, human; apoptosis; heart; reperfusion injury; transcription factor CHOP

Results 1-13 (13)