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1.  Dreams come true: the soul and spirit of orthopaedics 
PMCID: PMC3960481  PMID: 24595646
2.  The influence of patella height on soft tissue balance in cruciate-retaining and posterior-stabilised total knee arthroplasty 
International Orthopaedics  2012;37(3):421-425.
Although the patella reduced or everted position has recently been recognised as an important factor influencing soft tissue balance during assessment in total knee arthroplasty (TKA), the influence of patella height on soft tissue balance has not been well addressed. Therefore, the relationship between soft tissue balance and patella height was investigated and differences between cruciate-retaining (CR) and posterior-stabilised (PS) TKA were compared.
Forty consecutive patients blinded to the type of implant received, were randomised prospectively. Using lateral radiographs, pre-operative patella height was measured. Using an offset-type tensor designed to measure the soft tissue balance with a reduced patellofemoral (PF) joint and femoral component in place, soft tissue balance was intra-operatively assessed in CR TKA (n = 20) and PS TKA (n = 20) in osteoarthritic patients. The joint component gap and varus ligament balance at zero, ten, 45, 90 and 135° of knee flexion with the patella reduced were measured.
In PS TKA, the joint component gap positively correlated with patella height at 90 and 135° of knee flexion. However, there was no correlation between joint component gap and patella height at other flexion angles in PS TKA and any flexion angle in CR TKA. Varus ligament balance showed no significant correlation with patella height in either CR or PS TKA.
Analysis of soft tissue balance and patella height only showed a positive correlation in joint component gap at a high flexion angle (90 and 135°) in PS TKA but not in other parameters examined. Pre-operative measurement of patella height may be an important factor for predicting an intra-operative flexion gap in PS TKA.
PMCID: PMC3580105  PMID: 23275081
3.  Notochordal cell disappearance and modes of apoptotic cell death in a rat tail static compression-induced disc degeneration model 
The intervertebral disc has a complex structure originating developmentally from both the mesenchyme and notochord. Notochordal cells disappear during adolescence, which is also when human discs begin to show degenerative signs. During degeneration later in life, disc cells decline because of apoptosis. Although many animal models have been developed to simulate human disc degeneration, few studies have explored the long-term changes in cell population and phenotype. Our objective was to elucidate the time-dependent notochordal cell disappearance and apoptotic cell death in a rat tail static compression-induced disc degeneration model.
Twenty-four 12-week-old male Sprague–Dawley rat tails were instrumented with an Ilizarov-type device and loaded statically at 1.3 MPa for up to 56 days. Loaded and distal-unloaded discs were harvested. Changes in cell number and phenotype were assessed with histomorphology and immunofluorescence. Apoptosis involvement was determined with terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and immunohistochemistry.
The number of disc nucleus pulposus and annulus fibrosus cells decreased with the loading period; particularly, the decrease was notable at day 7 in larger, vacuolated, cytokeratin-8- and galectin-3-co-positive cells, indicating notochordal origin. Subsequently, the proportion of cells positive for TUNEL and cleaved caspase-3, markers of apoptosis induction, increased from day 7 through day 56. Although the percentage of cells immunopositive for cleaved caspase-8, a marker of apoptosis initiation through the death-receptor pathway, increased only at day 7, the percentage of cells immunopositive for cleaved caspase-9 and p53-regulated apoptosis-inducing protein 1 (p53AIP1), markers of apoptosis initiation through the p53-mediated mitochondrial pathway, increased from day 7 through day 56. The percentage of cells immunopositive for B-cell lymphoma 2 (Bcl-2) and silent mating type information regulation 2 homolog 1 (SIRT1), antiapoptotic proteins, decreased consistently with compression.
This rat tail model mimics notochordal cell disappearance and apoptotic cell death in human disc aging and degeneration. Sustained static compression induces transient activation of apoptosis through the death-receptor pathway and persistent activation of apoptosis through the p53-mediated mitochondrial pathway in disc cells. The increased proapoptotic and decreased antiapoptotic proteins observed at all time points signify static compression-induced disc cell death and degeneration.
PMCID: PMC3979117  PMID: 24472667
4.  Obese patients may have more soft tissue impingement following primary total hip arthroplasty 
International Orthopaedics  2012;36(12):2419-2423.
Several studies have reported a risk of dislocation in obese patients after total hip arthroplasty. In this study, we evaluated the interaction between obesity and dislocation by kinematic analysis using a navigation system.
The intraoperative range of motion (ROM) and postoperative impingement-free ROM were measured in 38 patients, and we compared the impingement-free ROM in obese and non obese patients.
The postoperatively simulated ROM was similar in the obese and non obese groups. The intraoperative ROM was smaller in the obese group. The difference values between the intraoperative ROM and postoperatively simulated ROM were larger in the obese group. These results indicate that obese patients have less ROM following primary total hip arthroplasty even when the implant positioning is performed correctly.
Dislocations are multifactorial problems including soft tissue impingement. Therefore, the risk of dislocation caused by soft tissue impingement in obese patients may be increased.
PMCID: PMC3508038  PMID: 23135350
5.  Osteochondral autograft transplantation for juvenile osteochondritis dissecans of the knee: a series of twelve cases 
International Orthopaedics  2012;36(11):2243-2248.
The purpose of this study was to evaluate the clinical outcomes of osteochondral autograft transplantation (OAT) for juvenile osteochondritis dissecans (JOCD) lesions of the knee, especially time to return to sports.
Twelve knee JOCD lesions with OCD grade 3 and 4 categorised by magnetic resonance imaging (MRI) were treated with OAT. Nine male and two female skeletally immature patients averaging 13.7 years old were included. The OCD lesions were assessed arthroscopically and then fixed in situ using multiple osteochondral plugs harvested under fluoroscopy from the distal femoral condyle without damaging the physis. International Cartilage Repair Society (ICRS) score and Lysholm score were assessed pre- and postoperatively.
After a mean follow-up of 26.2 ± 15.1 months, the International Knee Documentation Committee (IKDC) subjective score significantly improved (p < 0.01). According to the IKDC score, objective assessment showed that ten of 12 (83 %) had excellent results (score: A) after OAT and significantly improved (p < 0.01). Based on ICRS criteria, results were satisfactory in all patients. No patients experienced complications at the graft harvest site. All patients returned to their previous level of athletic activity at an average of 5.7 months after the surgery.
OAT for JOCD of the knee provided satisfactory results in all patients at a mean follow-up of 26.2 months.
PMCID: PMC3479294  PMID: 22955675
6.  Ligament regeneration using an absorbable stent-shaped poly-l-lactic acid scaffold in a rabbit model 
International Orthopaedics  2012;36(11):2379-2386.
Ligaments are frequently damaged in sports activities and trauma, and severe ligament injury can lead to joint instability and osteoarthritis. In this study, we aimed to regenerate the medial collateral ligament (MCL) using an absorbable stent-shaped poly-l-lactic acid (PLLA) scaffold in a rabbit model to examine the biocompatibility and mechanical properties.
Twenty-three Japanese white rabbits were used in this study. MCL defects were surgically created in the knee joints and then reconstructed using stent-shaped PLLA scaffolds. As controls, flexor digitorum longus (FDL) tendons were implanted into the contralateral knees. Seven rabbits were sacrificed at three time points, conducted four, eight and 16 weeks after the operation. The regenerated tissues were histologically evaluated using fibre alignment scoring, morphology of fibroblast scoring and immunohistochemical analysis of types I and III collagen. The regenerated tissues were also biomechanically evaluated by measuring the ultimate failure load and stiffness.
At four weeks post-operation, spindle-shaped cells were observed on the inside of the scaffolds. At eight weeks, maturation of the regenerated tissues and collagen fibre alignment parallel to the ligaments was observed. At 16 weeks, the fibre alignment had become denser. The fibre alignment and morphology of fibroblast scores significantly increased in a time-dependent manner. Expression of type I collagen was more strongly observed in the scaffold group at eight and 16 weeks post-operation than at four weeks. Type III collagen was also observed at four, eight and 16 weeks post-operation. A thin layer of fibrocartilage was observed at the ligament-bone junction at eight and 16 weeks. The ultimate failure load of the scaffold group was 46.7 ± 20.7 N, 66.5 ± 11.0 N and 74.3 ± 11.5 N at four, eight and 16 weeks post-operation, respectively. There was no statistical difference between the normal MCL and the scaffold group at 16 weeks post-operation.
The stent-shaped PLLA scaffold allowed for MCL regeneration with type I collagen expression and fibrocartilage formation and resulted in sufficient mechanical function.
PMCID: PMC3479301  PMID: 22976595
7.  In vivo comparisons of patellofemoral kinematics before and after ADVANCE® Medial-Pivot total knee arthroplasty 
International Orthopaedics  2012;36(10):2073-2077.
ADVANCE® Medial-Pivot (MP) (Wright Medical Technology, Arlington, TN, USA) total knee arthroplasty (TKA) was developed to replicate normal tibiofemoral knee joint kinematics, allowing medial-pivot knee motion. The design concept of the prosthesis is unique; therefore, the influence on the patellofemoral knee joint remains unclear at present. The purpose of this study was to determine the in vivo patellofemoral kinematics with ADVANCE® MP TKA and compare them with the pre-operative conditions.
ADVANCE® MP TKA was performed in ten subjects with osteoarthritis (OA). At before and one month after surgery, lateral radiographs with weight-bearing at maximum extension, 30, 60 and 90° were taken, and patella flexion angle (PF), tibiopatellar angle (TP) and estimated patellofemoral contact point (PC) were evaluated, according to a previously reported method.
In PF and TP, there was no statistically significant change between pre-operative and postoperative values. Pre-operative PC reached its peak at 90°; however, its peak was at 60° at one month after surgery. Postoperative PC at maximum extension was significantly higher compared to before surgery.
The results in this study indicated that ADVANCE® MP TKA changed patellofemoral joint kinematics compared to before surgery. Early postoperative evaluation is the limitation of this study; however, we consider that the results in this study might be one of the keys to resolving the kinematic features of this prosthesis, helping clinicians to comprehend this prosthesis.
PMCID: PMC3460083  PMID: 22885803
8.  Sequential MR Images and Radiographs of Epiphyseal Osteomyelitis in the Distal Femur of an Infant 
Case Reports in Radiology  2013;2013:672815.
Magnetic resonance imaging (MRI) plays an important role in the diagnosis of osteomyelitis, especially during the early phase of the disease. The findings of sequential MRIs during the course of treatment in acute osteomyelitis in children have not yet been reported in the literature. We present a case of acute epiphyseal osteomyelitis in the distal femur of an infant. We monitored imaging changes by sequential MRIs and radiographs. MRI was more useful than radiograph for early diagnosis and evaluation of therapeutic response.
PMCID: PMC3793311  PMID: 24175108
9.  Novel Surgical Treatment for Refractory Heel Ulcers in Werner's Syndrome 
Case Reports in Orthopedics  2013;2013:287025.
Patients with Werner's syndrome frequently develop chronic leg ulcers that heal poorly. We present a patient who suffered from this rare syndrome and developed typical heel ulcers. Treatment of the ulcer is challenging, as flap options are limited over the lower third of the leg and skin grafting is not easy as there is a lack of healthy granulations. We successfully treated the ulcer with osteomyelitis by drilling the bone and applying an ultrathin split thickness skin graft with the thigh skin as the donor site.
PMCID: PMC3770039  PMID: 24062960
10.  ‘Decoy’ and ‘non-decoy’ functions of DcR3 promote malignant potential in human malignant fibrous histiocytoma cells 
International Journal of Oncology  2013;43(3):703-712.
Decoy receptor 3 (DcR3) is a soluble secreted protein that belongs to the tumor necrosis factor receptor (TNFR) superfamily. DcR3 inhibits the Fas ligand (FasL)/Fas apoptotic pathway by binding to FasL, competitively with Fas receptor. Previous studies have reported that overexpression of DcR3 has been detected in various human malignancies and that DcR3 functions as a ‘decoy’ for FasL to inhibit FasL-induced apoptosis. In addition, recent studies have revealed that DcR3 has ‘non-decoy’ functions to promote tumor cell migration and invasion, suggesting that DcR3 may play important roles in tumor progression by decoy and non-decoy functions. We have previously reported that overexpression of DcR3 was observed in human malignant fibrous histiocytoma (MFH), however, the roles of DcR3 in MFH have not been studied. In the present study, to elucidate the roles of DcR3 in tumor progression of MFH, we examined the effects of DcR3 inhibition on cell apoptosis, migration and invasion in human MFH cells. siRNA knockdown of DcR3 enhanced the FasL-induced apoptotic activity and significantly decreased cell migration and invasion with a decrease in the activation of phosphatidylinositol 3 kinase (PI3K)/Akt and matrix metalloproteinase (MMP)-2. The findings in this study strongly suggest that DcR3 plays important roles in tumor progression of human MFH by decoy as well as non-decoy functions and that DcR3 may serve as a potent therapeutic target for human MFH.
PMCID: PMC3787885  PMID: 23817777
DcR3; apoptosis; migration; invasion; matrix metalloproteinase
11.  Periprosthetic bone mineral density with a cementless triple tapered stem is dependent on daily activity 
International Orthopaedics  2011;36(6):1137-1142.
Periprosthetic bone loss around the femoral stem is frequently found after total hip arthroplasty. We have shown that periprosthetic bone mineral density (BMD) loss using the triple tapered stem is consistently much less in comparison with the straight type component. In this study, we compared periprosthetic BMD change with clinical factors.
Postoperative dual-energy X-ray absorptiometry was evaluated at follow-up. BMD was determined based on seven Gruen zones. We further compared BMD with clinical examination: body mass index (BMI), age, Harris hip score (HHS) or University of California at Los Angeles (UCLA) activity rating score.
Periprosthetic BMD loss of the triple tapered stem was maintained. Especially, BMD in Gruen zone 1 which was maintained at 96% in comparison with the straight tapered stem. We compared the BMD change with clinical factors. There is no correlation between BMD and BMI, age or HHS. However, we found significant correlation between BMD and UCLA activity rating score in Gruen zones 1 and 2 of the triple tapered stem. Further, the correlation coefficient was increased at 48 months in comparison with 24 months.
The cementless triple tapered stem maintains periprosthetic bone mineral density. Activity may reflect improving periprosthetic bone quality after THA using a triple tapered stem.
Electronic supplementary material
The online version of this article (doi:10.1007/s00264-011-1407-3) contains supplementary material, which is available to authorized users.
PMCID: PMC3353079  PMID: 22127382
12.  Development of percutaneously insertable/removable interspinous process spacer for treatment of posture-dependent lumbar spinal-canal stenosis: preclinical feasibility study using porcine model 
European Spine Journal  2011;21(6):1178-1185.
A procedure using an interspinous process spacer (IPS) was recently developed for the treatment of posture-dependent lumbar spinal-canal stenosis (LSS) patients. We developed a novel IPS which can be inserted with simpler procedures and removed percutaneously. The objectives of this study were: (1) to evaluate the feasibility and safety of this novel technique, and (2) to assess the effectiveness of this spacer in terms of preventing an increase of epidural pressure in lumbar extension using a porcine model.
Eight young pigs were used. Under general anesthesia and image guidance, the spacers were inserted. Three months after operation, MR images were taken and all spacers were removed. Blood samples were obtained before and 1, 3, 7 days after surgery. After killing the animals, the lumbar spines were observed macroscopically. Another six animals were used. Under general anesthesia and image guidance, a flexible pressure transducer was inserted into the epidural space and epidural pressure was measured in neutral and at maximum extension with and without spacer insertion.
Percutaneous insertion and removal of the spacer was successful for all animals through small skin incisions. MR images showed minimal damage to the muscle. No significant up-regulation of Interleukin-6 (IL-6) and CRP was detected. Macroscopic observation of the lumbar spine 3 months after the operation revealed that the area of the interspinous process contacting with the inserted spacer showed some bone erosion/remodeling. Insertion of the spacer did not affect the epidural pressure in neutral but significantly prevented an increase of epidural pressure in lumber extension.
This study demonstrated that the percutaneous insertion and removal of a novel IPS was feasible and safe using a simple technique. Furthermore, this procedure can be recognized as minimally invasive surgery from the viewpoint of skin incision, short insertion track, inflammatory mediators, and muscle damage. Improvements should be attempted in future studies using softer or more elastic materials for the spacer to lessen bone erosion/remodeling at contacting area of the inserted spacer.
PMCID: PMC3366124  PMID: 22201010
Lumbar spinal-canal stenosis; Minimally invasive surgery; Interspinous process spacer; Big animal study; Epidural pressure
13.  Breakage of a Third Generation Gamma Nail: A Case Report and Review of the Literature 
Case Reports in Orthopedics  2013;2013:172352.
The use of intramedullary nails to treat trochanteric fractures of the femur has increased with the increasing size of the elderly population. The third generation Gamma nail is currently one of the most popular devices for the treatment of trochanteric fractures. Nail breakage is a rare complication, possibly resulting from fatigue fracture of the implant. We present the first reported case of breakage of a third generation Gamma nail that was not used to treat a pathological fracture. An 83-year-old woman with an unstable trochanteric fracture of the femur was treated using a third generation Gamma nail. She was referred to our hospital 14 months postoperatively with nail breakage at the opening for the lag screw. The breakage was secondary to nonunion, which was thought to be mainly due to insufficient reduction of the fracture. The broken nail was removed, and the patient underwent cemented bipolar hemiarthroplasty. At followup 18 months later, she was mobile with a walker and asymptomatic with no complications. This case shows that inadequate operation such as insufficient reduction of the trochanteric fracture may result in nonunion and implant breakage, even when using a high-strength, well-designed implant.
PMCID: PMC3671522  PMID: 23762698
14.  Soft tissue balance using the tibia first gap technique with navigation system in cruciate-retaining total knee arthroplasty 
International Orthopaedics  2011;36(5):975-980.
The procedures of bone cut and soft tissue balancing in total knee arthroplasty (TKA) are usually performed using the measured resection technique or the gap technique; however, the superiority of these techniques is controversial. An increase of extension gap after resection of the femoral posterior condyle and a difference between gaps before and after femoral component placement have been reported. We therefore postulated that the use of the tibia first gap technique might have an advantage in avoiding the mismatch before and after resection of the femoral posterior condyle and femoral component placement.
We performed cruciate-retaining TKAs for 60 varus type osteoarthritic patients with tibia first gap technique using a CT-free navigation system. A TKA tensor designed to facilitate soft tissue balance measurements throughout the range of motion with a reduced and repaired patello-femoral joint was used to assess soft tissue balance (joint gap and varus ligament balance) at extension and flexion between the basic value after tibial cut and the final value following femoral cut and with the femoral component in place.
Whereas varus ligament balance at flexion showed significant decrease in the final value at flexion due to the amount of femoral rotation, the basic value of the joint gap before femoral osteotomy reflected the final value following femoral cut and with the femoral component in place.
The tibia first gap technique may have the advantage that surgeons can predict final soft tissue balance before femoral osteotomies.
PMCID: PMC3337096  PMID: 22038438
Medicine & Public Health; Orthopedics
15.  Sacral Fracture Nonunion Treated by Bone Grafting through a Posterior Approach 
Case Reports in Orthopedics  2013;2013:932521.
Nonunion of a sacral fracture is a rare but serious clinical condition which can cause severe chronic pain, discomfort while sitting, and significant restriction of the level of activities. Fracture nonunions reportedly occur most often after nonoperative initial treatment or inappropriate operative treatment. We report a case of fracture nonunion of the sacrum and pubic rami that resulted from non-operative initial treatment, which was treated successfully using bone grafting through a posterior approach and CT-guided percutaneous iliosacral screw fixation combined with anterior external fixation. Although autologous bone grafting has been the gold standard for the treatment of pelvic fracture nonunions, little has been written describing the approach. We utilized a posterior approach for bone grafting, which could allow direct visualization of the nonunion site and preclude nerve root injury. By this procedure, we were able to obtain the healing of fracture nonunion, leading to pain relief and functional recovery.
PMCID: PMC3657433  PMID: 23738173
16.  Isolation and Characterization of Human Anterior Cruciate Ligament-Derived Vascular Stem Cells 
Stem Cells and Development  2011;21(6):859-872.
The anterior cruciate ligament (ACL) usually fails to heal after rupture mainly due to the inability of the cells within the ACL tissue to establish an adequate healing process, making graft reconstruction surgery a necessity. However, some reports have shown that there is a healing potential of ACL with primary suture repair. Although some reports showed the existence of mesenchymal stem cell-like cells in human ACL tissues, their origin still remains unclear. Recently, blood vessels have been reported to represent a rich supply of stem/progenitor cells with a characteristic expression of CD34 and CD146. In this study, we attempted to validate the hypothesis that CD34- and CD146-expressing vascular cells exist in hACL tissues, have a potential for multi-lineage differentiation, and are recruited to the rupture site to participate in the intrinsic healing of injured ACL. Immunohistochemistry and flow cytometry analysis of hACL tissues demonstrated that it contains significantly more CD34 and CD146-positive cells in the ACL ruptured site compared with the noninjured midsubstance. CD34+CD45− cells isolated from ACL ruptured site showed higher expansionary potentials than CD146+CD45− and CD34−CD146−CD45− cells, and displayed higher differentiation potentials into osteogenic, adipogenic, and angiogenic lineages than the other cell populations. Immunohistochemistry of fetal and adult hACL tissues demonstrated a higher number of CD34 and CD146-positive cells in the ACL septum region compared with the midsubstance. In conclusion, our findings suggest that the ACL septum region contains a population of vascular-derived stem cells that may contribute to ligament regeneration and repair at the site of rupture.
PMCID: PMC3871494  PMID: 21732814
17.  Nonunion with Breakage of Gamma Nail and Subsequent Fracture in the Ipsilateral Femur 
Case Reports in Medicine  2013;2013:534570.
We describe a rare case with breakage of gamma nail accompanied by nonunion of the original fracture and a subsequent new fracture in the ipsilateral femur. A 73-year-old woman suffered a subtrochanteric fracture of the femur, and the fracture was fixed with gamma nail at a previous hospital. However, fracture reduction was not adequately achieved and a large gap remained between the fracture fragments. The fracture demonstrated atrophic nonunion 10 months after surgery, and autologous bone grafting was performed at the same hospital. Two months after the second surgery, a breakage of the nail at the distal screw hole was observed. Twenty-six months after the second surgery, the patient fell and a fracture occurred at the level of the nail breakage. The atrophic nonunion site and fresh fracture site were very close thus demonstrating a segmental fracture. We exchanged the original gamma nail with a long gamma nail and performed autologous bone grafting at the nonunion site. Both the fresh fracture site and the nonunion site obtained bony union. This tragic chain of events was caused by inappropriate initial treatment and replacing the nail to a longer nail and autologous bone grafting were effective as salvage surgery.
PMCID: PMC3600130  PMID: 23533430
18.  Radiation-Associated Fracture Nonunion of the Clavicle Treated with Locking Plate Fixation and Autologous Bone Grafting 
Case Reports in Medicine  2012;2012:407349.
We describe a case of radiation-associated fracture nonunion of the clavicle, which was treated by locking plate fixation and autologous bone grafting. The patient was a 67-year old man who received 70 Gy radiation therapy to treat nasopharyngeal carcinoma. Eight years later, he suffered a pathological fracture of the right clavicle. One year after the fracture, surgical treatment was performed due to persistent pain and weakness. Radiographs demonstrated atrophic nonunion. Bone scan demonstrated hot uptake at both ends of the fractured bone. MRI demonstrated a formation of pseudoarthrosis with fluid collection and suggested bone marrow edema at both ends of the fracture fragments. In surgery, fibrous pseudoarthrosis tissue was excised and both ends of the fracture fragments were refreshed to identify bleeding. Open reduction and internal fixation using a 7-hole locking plate and autologous bone grafting were performed. Successful bony union was obtained 1 year postoperatively, and no adverse events were observed up to 52 months after the operation. Our case suggests that a locking plate provides sufficient fixation and autologous bone grafting is effective in enhancing bone healing in a radiation-associated fracture nonunion of the clavicle in which it is difficult to achieve bony union.
PMCID: PMC3541794  PMID: 23326273
19.  A Case of Acute Prosthesis Migration after Femoral Head Replacement due to Osteomalacia by FGF23-Induced Tumor 
Case Reports in Medicine  2012;2012:503956.
Fibroblast growth factor 23 (FGF23) was recently identified as an important factor involved in the development of hypophosphatemic rickets and osteomalacia. We experienced a rare case of acute prosthesis migration after hemihip arthroplasty due to FGF23-induced tumor. The patient underwent femoral head replacement because of femoral neck fracture, but prosthesis migration was occurred at 1 week after operation. The patient took various examinations, and FGF23-induced tumor was found in his right wrist. The tumor was resected, and he underwent total hip arthroplasty 8 month later. Finally, he was able to obtain free gait without pain.
PMCID: PMC3521639  PMID: 23251177
20.  Transcutaneous Application of Carbon Dioxide (CO2) Induces Mitochondrial Apoptosis in Human Malignant Fibrous Histiocytoma In Vivo 
PLoS ONE  2012;7(11):e49189.
Mitochondria play an essential role in cellular energy metabolism and apoptosis. Previous studies have demonstrated that decreased mitochondrial biogenesis is associated with cancer progression. In mitochondrial biogenesis, peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) regulates the activities of multiple nuclear receptors and transcription factors involved in mitochondrial proliferation. Previously, we showed that overexpression of PGC-1α leads to mitochondrial proliferation and induces apoptosis in human malignant fibrous histiocytoma (MFH) cells in vitro. We also demonstrated that transcutaneous application of carbon dioxide (CO2) to rat skeletal muscle induces PGC-1α expression and causes an increase in mitochondrial proliferation. In this study, we utilized a murine model of human MFH to determine the effect of transcutaneous CO2 exposure on PGC-1α expression, mitochondrial proliferation and cellular apoptosis. PGC-1α expression was evaluated by quantitative real-time PCR, while mitochondrial proliferation was assessed by immunofluorescence staining and the relative copy number of mitochondrial DNA (mtDNA) was assessed by real-time PCR. Immunofluorescence staining and DNA fragmentation assays were used to examine mitochondrial apoptosis. We also evaluated the expression of mitochondrial apoptosis related proteins, such as caspases, cytochorome c and Bax, by immunoblot analysis. We show that transcutaneous application of CO2 induces PGC-1α expression, and increases mitochondrial proliferation and apoptosis of tumor cells, significantly reducing tumor volume. Proteins involved in the mitochondrial apoptotic cascade, including caspase 3 and caspase 9, were elevated in CO2 treated tumors compared to control. We also observed an enrichment of cytochrome c in the cytoplasmic fraction and Bax protein in the mitochondrial fraction of CO2 treated tumors, highlighting the involvement of mitochondria in apoptosis. These data indicate that transcutaneous application of CO2 may represent a novel therapeutic tool in the treatment of human MFH.
PMCID: PMC3499556  PMID: 23166610
21.  Intra-articular injection of tranexamic acid reduces not only blood loss but also knee joint swelling after total knee arthroplasty 
International Orthopaedics  2011;35(11):1639-1645.
This is a randomised controlled trial to examine whether intra-articular injection of tranexamic acid (TXA) decreases blood loss, as well as reducing leg swelling after total knee arthroplasty (TKA).
We performed 100 TKA in osteoarthritis patients. At closure, a total of 2,000 mg/20 ml TXA was injected into the knee joint through a closed suction drain (TXA group). For the control group, the same volume of physiological saline was injected. The pre-operative condition of the patients, post-operative haemoglobin (Hb) levels, discharge volumes from drain, D-dimer and needs for transfusion were compared between these two groups. Furthermore, leg diameters (thigh, suprapatellar portion and calf girth) were measured pre- and post-operatively to investigate whether TXA has an influence on leg swelling after surgery.
The results revealed that post-operative decrease in Hb level was significantly reduced in the TXA group. Furthermore, knee joint swelling after operation was significantly suppressed in the TXA group compared to the control group.
The results revealed intra-articular administration of TXA decreased not only blood loss, but also knee joint swelling after TKA.
PMCID: PMC3193960  PMID: 21253725
22.  Autogenous osteochondral graft transplantation for steroid-induced osteonecrosis of the femoral condyle: A report of three young patients 
Steroid-induced osteonecrosis of the femoral condyle is a relatively uncommon condition and is often difficult to select appropriate treatment especially in young patients. Three young men (aged 25, 18, and 24) presented with severe pain and dysfunction of the knee diagnosed as steroid-induced osteonecrosis of the femoral condyle by magnetic resonance imaging (MRIs). Full-thickness cartilage defects sized 20 × 10, 15 × 10, and 30 × 20 mm respectively were classified as International Cartilage Repair Society Grade IV lesions and treated with osteochondral autograft transplantation. They were treated successfully with osteochondral autograft transplantation certificated by post-operative MRI and second look arthroscopy.
PMCID: PMC3414816  PMID: 22537556
Steroid-induced osteonecrosis; Osteochodral autograft transplantation; Mosaicplasty; Femoral condyle
23.  Bilateral Insufficiency Fracture of the Pelvis Following THA: A Case Report 
Case Reports in Medicine  2012;2012:170736.
Insufficiency fracture is of the stress fractures and is caused by repetitive stress on fragile bone. Insufficiency fractures of pubic rami are rare occurrences in association with total hip arthroplasty (THA). Postoperative stress fractures occur due to increase of patients activity following years of disability. The physician should consider the possibility of a pelvic insufficiency fracture in patients with RA after THA, if the patients present with groin pain. We demonstrate here the first case of bilateral insufficiency fracture of pubic rami and iliac bone following THA.
PMCID: PMC3318264  PMID: 22536261
24.  Rat tail static compression model mimics extracellular matrix metabolic imbalances of matrix metalloproteinases, aggrecanases, and tissue inhibitors of metalloproteinases in intervertebral disc degeneration 
The longitudinal degradation mechanism of extracellular matrix (ECM) in the interbertebral disc remains unclear. Our objective was to elucidate catabolic and anabolic gene expression profiles and their balances in intervertebral disc degeneration using a static compression model.
Forty-eight 12-week-old male Sprague-Dawley rat tails were instrumented with an Ilizarov-type device with springs and loaded statically at 1.3 MPa for up to 56 days. Experimental loaded and distal-unloaded control discs were harvested and analyzed by real-time reverse transcription-polymerase chain reaction (PCR) messenger RNA quantification for catabolic genes [matrix metalloproteinase (MMP)-1a, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and ADAMTS-5], anti-catabolic genes [tissue inhibitor of metalloproteinases (TIMP)-1, TIMP-2, and TIMP-3], ECM genes [aggrecan-1, collagen type 1-α1, and collagen type 2-α1], and pro-inflammatory cytokine genes [tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1β, and IL-6]. Immunohistochemistry for MMP-3, ADAMTS-4, ADAMTS-5, TIMP-1, TIMP-2, and TIMP-3 was performed to assess their protein expression level and distribution. The presence of MMP- and aggrecanase-cleaved aggrecan neoepitopes was similarly investigated to evaluate aggrecanolytic activity.
Quantitative PCR demonstrated up-regulation of all MMPs and ADAMTS-4 but not ADAMTS-5. TIMP-1 and TIMP-2 were almost unchanged while TIMP-3 was down-regulated. Down-regulation of aggrecan-1 and collagen type 2-α1 and up-regulation of collagen type 1-α1 were observed. Despite TNF-α elevation, ILs developed little to no up-regulation. Immunohistochemistry showed, in the nucleus pulposus, the percentage of immunopositive cells of MMP-cleaved aggrecan neoepitope increased from 7 through 56 days with increased MMP-3 and decreased TIMP-1 and TIMP-2 immunopositivity. The percentage of immunopositive cells of aggrecanase-cleaved aggrecan neoepitope increased at 7 and 28 days only with decreased TIMP-3 immunopositivity. In the annulus fibrosus, MMP-cleaved aggrecan neoepitope presented much the same expression pattern. Aggrecanase-cleaved aggrecan neoepitope increased at 7 and 28 days only with increased ADAMTS-4 and ADAMTS-5 immunopositivity.
This rat tail sustained static compression model mimics ECM metabolic imbalances of MMPs, aggrecanases, and TIMPs in human degenerative discs. A dominant imbalance of MMP-3/TIMP-1 and TIMP-2 relative to ADAMTS-4 and ADAMTS-5/TIMP-3 signifies an advanced stage of intervertebral disc degeneration.
PMCID: PMC3446417  PMID: 22394620
25.  A prospective randomised study of anatomical single-bundle versus double-bundle anterior cruciate ligament reconstruction: quantitative evaluation using an electromagnetic measurement system 
International Orthopaedics  2010;35(3):439-446.
We conducted a prospective randomised study of anatomical single-bundle (A-SB group) versus double-bundle (A-DB group) anterior cruciate ligament (ACL) reconstruction using the hamstrings tendons. Twenty patients with unilateral ACL deficiency were randomised into two groups. We created the bone tunnels at the position of the original insertion of the anteromedial bundle footprint and posterolateral bundle footprint in the A-DB group and at the central position between these two bundles in the A-SB group. All of the patients were tested before ACL reconstruction and one year after surgery. The KT-1000 measurements, isokinetic muscle peak torque and heel-height difference were evaluated and the general knee condition was assessed by Lysholm score. For pre- and postoperative stability assessment, we used the six-degrees-of-freedom of knee kinematic measurement system using an electromagnetic device (the EMS) for quantitative assessment during the Lachman test and the pivot shift test. There were no significant differences in the KT-1000 measurements, isokinetic muscle peak torque, heel-height difference, and Lysholm score at one-year follow-up between these two groups. The EMS data showed there were significant differences in the acceleration of the pivot shift test between the operated knee and the contralateral normal knees in the A-SB group. In conclusion, clinical outcomes were equally good in both groups. However, the EMS data showed the anatomical double-bundle ACL reconstruction tended to be biomechanically superior to the single-bundle reconstruction.
PMCID: PMC3047641  PMID: 20734043

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