Complete traumatic backout of the blade of proximal femoral nail antirotation: a case report.

This article presents a rare case of traumatic complete expulsion of the helical blade after successful treatment of an intertrochanteric fracture with proximal femoral nail antirotation (PFNA). A 94-year-old woman sustained an intertrochanteric fracture of the left femur. Fracture fixation was performed by using PFNA-II. At six months FU, the patient presented with pain at the proximal lateral left thigh after she had fallen. A protrusion was noted. Radiographs showed a complete expulsion of the helical blade with a healed intertrochanteric fracture. The PFNA-II was removed and a cemented bipolar hemiarthroplasty was performed. At 5 months after surgery, the patient was able to walk with a walker without pain. Traumatic complete expulsion of the blade should be considered as a possible complication of PFNA/PFNA-II.

The osteogenic activity of human mandibular fracture haematoma-derived cells is stimulated by low-intensity pulsed ultrasound in vitro.

Low intensity pulsed ultrasound (LIPUS) stimulation is a clinically established treatment method used to accelerate long bone fracture healing; however, this method is currently not applied to mandibular fractures. In this study, we investigated the effects of LIPUS on human mandibular fracture haematoma-derived cells (MHCs) in order to explore the possibility of applying LIPUS treatment to mandibular fractures. MHCs were isolated from five patients. The cells were divided into two groups: (1) LIPUS (+) group: MHCs cultured in osteogenic medium with LIPUS treatment; and (2) LIPUS (-) group: MHCs cultured in osteogenic medium without LIPUS treatment. The osteogenic differentiation potential and proliferation of the MHCs were compared between the two groups. The waveform used was equal to the wave conditions of a clinical fracture healing system. The gene expression levels of ALP, OC, Runx2, OSX, OPN, and PTH-R1 and mineralization were increased in the LIPUS (+) group compared to the LIPUS (-) group. There were no significant differences in cell proliferation between the two groups. These findings demonstrate the significant effects of LIPUS on the osteogenic differentiation of MHCs. This study provides significant evidence for the potential usefulness of the clinical application of LIPUS to accelerate mandibular fracture healing.

Interleukin-6-induced satellite cell proliferation is regulated by induction of the JAK2/STAT3 signalling pathway through cyclin D1 targeting.

OBJECTIVES: To determine whether interleukin-6 (IL-6) stimulates rat muscle satellite cell proliferation in culture, and if so, to clarify the signalling mechanisms. MATERIALS AND METHODS: Primary satellite cells were isolated from thirty male F344 rats, 11 weeks of age. IL-6 at concentrations of 0.01, 0.1, 1, 10 or 100 ng/ml was added to culture media. RESULTS: IL-6 at 0.01-1 ng/ml induced dose-dependent increase in cell proliferation. After treatment with 1 ng/ml IL-6, cell proliferation increased by 31%, and p-STAT3(+) /MyoD(+) cells increased in number compared to those in control media (P < 0.05). Inhibitors of JAK2 (AG 490) and STAT3 (STAT3 peptide) blocked the increase in BrdUrd(+) cell numbers at 6 h post stimulation with 1 ng/ml IL-6 (P < 0.05). Furthermore, cyclin D1 mRNA expression and cyclin D1(+) /MyoD(+) cell numbers significantly increased in cultures treated with 1 ng/ml IL-6 compared to those in control media (P < 0.05). In contrast, treatment with 10 and 100 ng/ml IL-6 did not stimulate cell proliferation. Treatment with 10 ng/ml IL-6 induced greater SOCS3 mRNA expression than with 1 ng/ml IL-6 and control media. Moreover, co-localization of SOCS3 and myogenin was observed after treatment with 10 ng/ml IL-6. CONCLUSIONS: IL-6 induced dose-dependent increase in satellite cell proliferation by activating the JAK2/STAT3/cyclin D1 pathway.

Akt phosphorylation in human chondrocytes is regulated by p53R2 in response to mechanical stress.

OBJECTIVE: The p53 tumor-suppressor protein p53R2 is activated in response to various stressors that act on cell signaling. When DNA is damaged, phosphorylation of p53 at its Ser 15 residue induces p53R2 production. The role of p53R2 in chondrocytes remains poorly understood. In this study, we evaluated in chondrocytes, p53R2 expression and its regulation in response to mechanical stress. Furthermore, we investigated the function of p53R2 in relation to mechanotransduction. METHODS: Osteoarthritis (OA) cartilage obtained from total knee replacements and normal cartilage obtained from femoral neck fractures was used to measure p53R2 expression by using immunohistochemistry, western blotting, and real-time polymerase chain reaction (PCR). The OA chondrocytes were subjected to a high magnitude of cyclical tensile strain by using an FX-2000 Flexercell system. Next, sulfated glycosaminoglycan (sGAG) production was quantified in these cells. Protein expression of p53R2, and phosphorylation of Akt, p38MAPK, ERK1/2, and JNK was also detected using western blotting. Moreover, Akt phosphorylation was detected after transfecting the cells with p53R2-specific small interfering RNA (siRNA). RESULTS: Expression of p53R2 was significantly increased in OA chondrocytes and in chondrocytes after applying 5% tensile strain to the cells. However, Akt phosphorylation was down-regulated in OA chondrocytes after the strain, and was up-regulated after transfection of p53R2. sGAG protein as well as collagen type II and aggrecan mRNA was increased following transfection of p53R2-specific siRNA after 5% tensile strain. CONCLUSIONS: p53R2 could regulate matrix synthesis via Akt phosphorylation during chondrocyte mechanotransduction. Down-regulation of p53R2 may be a new therapeutic approach in OA therapy.

Satellite cell pool enhancement in rat plantaris muscle by endurance training depends on intensity rather than duration.

AIM: Increases in the number of satellite cells are necessary for the maintenance of normal muscle function. Endurance training enhances the satellite cell pool. However, it remains unclear whether exercise intensity or exercise duration is more important to enhance the satellite cell pool. This study examined the effects of different intensity and duration of endurance training on the satellite cell pool in rat skeletal muscle. METHODS: Forty-one 17-week-old female Sprague-Dawley rats were assigned to control (n = 8), high intensity and high duration (n = 7), high intensity and low duration (n = 8), low intensity and high duration (n = 9) and low intensity and low duration (n = 9) groups. Training groups exercised 5 days per week on a motor driven treadmill for 10 weeks. After the training period, animals were anaesthetized and the plantaris muscles were removed, weighed and analysed for immunohistochemical and histochemical properties. RESULTS: Although no significant differences were found in muscle mass, mean fibre area and myonuclei per muscle fibre between all groups, the percentage of satellite cells was significantly higher in the high-intensity groups than in the other groups (P < 0.05). CONCLUSION: Increases in the satellite cell pool of skeletal muscle following endurance training depend on the intensity rather than duration of exercise.

Boron neutron capture therapy for clear cell sarcoma (CCS): biodistribution study of p-borono-L-phenylalanine in CCS-bearing animal models.

Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake l-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of (10)B (45-74 ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of L-BPA-fructose complex (500 mg BPA/kg).

Evaluation of BPA uptake in clear cell sarcoma (CCS) in vitro and development of an in vivo model of CCS for BNCT studies.

Clear cell sarcoma (CCS), a rare malignant tumor with a predilection for young adults, is of poor prognosis. Recently however, boron neutron capture therapy (BNCT) with the use of p-borono-L-phenylalanine (BPA) for malignant melanoma has provided good results. CCS also produces melanin; therefore, the uptake of BPA is the key to the application of BNCT to CCS. We describe, for the first time, the high accumulation of boron in CCS and the CCS tumor-bearing animal model generated for BNCT studies.

DcR3 induces cell proliferation through MAPK signaling in chondrocytes of osteoarthritis.

INTRODUCTION: Decoy receptor 3 (DcR3), a soluble receptor belonging to the tumor necrosis factor (TNF) receptor superfamily, competitively binds and inhibits the TNF family including Fas-ligand (Fas-L), lymphotoxin-like inducible protein that competes with glycoprotein D for binding herpesvirus entry mediator on T-cells (LIGHT) and TNF-like ligand 1A (TL1A). In this study, we investigated the functions of DcR3 on osteoarthritis (OA) chondrocytes. METHODS: Expressions of DcR3 in chondrocytes were measured by realtime Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). Expression of DcR3 in sera and joint fluids was measured by enzyme-linked immunosorbent assay (ELISA). Chondrocytes were incubated with DcR3-Fc chimera protein (DcR3-Fc) before induction of apoptosis by Fas-L and apoptosis was detected with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labelling labeling (TUNEL) staining and Western blotting of caspase 8 and poly (ADP-ribose) polymerase (PARP). Chondrocytes were incubated with DcR3-Fc and the proliferation was analyzed by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST) assay. Phosphorylation of Extracellular Signal-Regulated Kinase (ERK), P38 mitogen-activated protein kinase (MAPK) and Jun N-terminal Kinase (JNK) in chondrocytes was measured by Western blotting after incubation with DcR3-Fc, Mitogen-activated protein kinase kinase (MEK1/2) inhibitor, or P38 MAPK inhibitor. Chondrocytes were treated with DcR3-Fc after pre-incubation with blocking antibody of Fas-L, LIGHT and TL1A, and proliferation or phosphorylation of ERK was analyzed. RESULTS: DcR3 was expressed in OA and normal chondrocytes. DcR3-Fc protects chondrocytes from Fas-induced apoptosis. DcR3-Fc increased chondrocytes proliferation and induced the phosphorylation of ERK specifically. DcR3-induced chondrocytes proliferation was inhibited by pre-incubation of PD098059 or blocking Fas-L antibody. DcR3 increased chondrocytes proliferation in OA chondrocytes, but did not in normal. CONCLUSION: DcR3 regulates the proliferation of OA chondrocytes via ERK signaling and Fas-induced apoptosis.

The impact of early rehabilitation on the duration of hospitalization in patients after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: We examined the relationship between the improved physical activity by early rehabilitation and the duration of hospitalization among patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Thirteen allo-HSCT patients with myeloablative conditioning regimens (group A) and 13 patients with nonmyeloablative conditioning regimens (group B) were assessed retrospectively in this study. All patients received physical exercise immediately after neutrophil engraftment at the class 10,000 bioclean room (class 10,000). The mean daily steps at class 10,000 were measured as a substitute for the amount of physical activity, and the duration of hospitalization as one of the clinical outcomes. RESULTS: The degree of physical activity showed a negative correlation with the duration of hospitalization in group A (r = -.71; P = .0071), regardless of complications such as acute graft-versus-host disease, infections, and cytomegalovirus reactivation. However, there was no significant association in group B (r = .09; P = .77). CONCLUSION: The improved physical activity through early rehabilitation may be an independent, favorable prognostic factor for allo-HSCT patients with myeloablative conditioning regimens.

Efficient cell-seeding into scaffolds improves bone formation.

Bone marrow stromal cells (BMSCs)/beta-tricalcium phosphate (beta-TCP) composites have attracted a great deal of attention in bone tissue engineering. If more effective bone regeneration is to be achieved, efficient cell-seeding systems need to be clarified. In this study, we investigated the number of cells contained in composites, and the in vitro/vivo osteogenic differentiation capacity of composites using 4 conventional systems of seeding rat BMSCs into beta-TCP: soak, low-pressure, pipette, and syringe systems. The highest number of cells was contained in the composites from the syringe group. Moreover, after two-week osteogenic induction in vitro, the composites in the syringe group exhibited the highest osteogenic potential, which continued at 8 weeks after subcutaneous implantation in vivo. Our results indicated that efficient and appropriate cell-seeding could improve in vitro/vivo bone formation in composites and thus make a potential clinical contribution to successful bone tissue engineering.

Acetabular development in the contralateral hip in patients with unilateral developmental dysplasia of the hip.

BACKGROUND: Adult patients may present with acetabular dysplasia without a history of developmental dysplasia of the hip. The purpose of the present study was to clarify the development of primary acetabular dysplasia in patients under the age of eighteen years by evaluating the contralateral hip in those with unilateral developmental dysplasia of the hip. METHODS: Radiographs of the contralateral hip of eighty-eight patients with unilateral developmental dysplasia of the hip were reviewed retrospectively. The center-edge angle was measured at the age of eighteen years. The primary acetabular dysplasia group included hips with a center-edge angle of <20 degrees , and the normal group included hips with an angle of > or =20 degrees . The acetabular index at the age of three years, the center-edge angle between the ages of three and eighteen years, and the acetabular angle of Sharp between the ages of six and eighteen years were measured. RESULTS: According to our classification system, twelve hips (13.6%) were assigned to the primary acetabular dysplasia group. At the age of three years, there were no significant differences between the two groups radiographically. A significant difference in the center-edge angle between the two groups was seen at each evaluation period after the age of six years. However, twenty-two patients in the normal group had poor acetabular coverage and three patients in the primary acetabular dysplasia group had good acetabular coverage at the age of nine years. After the age of nine years, improvements in the center-edge angle and the acetabular angle of Sharp were noted in the normal group, whereas no acetabular growth was seen in the primary acetabular dysplasia group. There was no patient with a center-edge angle of <15 degrees at the age of twelve years in the normal group. CONCLUSIONS: After the age of six years, a difference in acetabular growth develops between patients with primary acetabular dysplasia and those with normal hips. However a final prognosis for acetabular development appears to be difficult to determine until the age of twelve years.

Accumulation of MRI contrast agents in malignant fibrous histiocytoma for gadolinium neutron capture therapy.

Neutron-capture therapy with gadolinium (Gd-NCT) has therapeutic potential, especially that gadolinium is generally used as a contrast medium in magnetic resonance imaging (MRI). The accumulation of gadolinium in a human sarcoma cell line, malignant fibrosis histiocytoma (MFH) Nara-H, was visualized by the MRI system. The commercially available MRI contrast medium Gd-DTPA (Magnevist, dimeglumine gadopentetate aqueous solution) and the biodegradable and highly gadopentetic acid (Gd-DTPA)-loaded chitosan nanoparticles (Gd-nanoCPs) were prepared as MRI contrast agents. The MFH cells were cultured and collected into three falcon tubes that were set into the 3-tesra MRI system to acquire signal intensities from each pellet by the spin echo method, and the longitudinal relaxation time (T1) was calculated. The amount of Gd in the sample was measured by inductively coupled plasma atomic emission spectrography (ICP-AES). The accumulation of gadolinium in cells treated with Gd-nanoCPs was larger than that in cells treated with Gd-DTPA. In contrast, and compared with the control, Gd-DTPA was more effective than Gd-nanoCPs in reducing T1, suggesting that the larger accumulation exerted the adverse effect of lowering the enhancement of MRI. Further studies are warranted to gain insight into the therapeutic potential of Gd-NCT.

The intra-operative joint gap in cruciate-retaining compared with posterior-stabilised total knee replacement.

We have developed a new tensor for total knee replacements which is designed to assist with soft-tissue balancing throughout the full range of movement with a reduced patellofemoral joint. Using this tensor in 40 patients with osteoarthritis we compared the intra-operative joint gap in cruciate-retaining and posterior-stabilised total knee replacements at 0 degrees , 10 degrees , 45 degrees , 90 degrees and 135 degrees of flexion, with the patella both everted and reduced. While the measurement of the joint gap with a reduced patella in posterior-stabilised knees increased from extension to flexion, it remained constant for cruciate-retaining joints throughout a full range of movement. The joint gaps at deep knee flexion were significantly smaller for both types of prosthetic knee when the patellofemoral joint was reduced (p < 0.05).

Osteogenic activity of human fracture haematoma-derived progenitor cells is stimulated by low-intensity pulsed ultrasound in vitro.

The haematoma occurring at the site of a fracture is known to play an important role in bone healing. We have recently shown the presence of progenitor cells in human fracture haematoma and demonstrated that they have the capacity for multilineage mesenchymal differentiation. There have been many studies which have shown that low-intensity pulsed ultrasound (LIPUS) stimulates the differentiation of a variety of cells, but none has investigated the effects of LIPUS on cells derived from human fracture tissue including human fracture haematoma-derived progenitor cells (HCs). In this in vitro study, we investigated the effects of LIPUS on the osteogenic activity of HCs. Alkaline phosphatase activity, osteocalcin secretion, the expression of osteoblast-related genes and the mineralisation of HCs were shown to be significantly higher when LIPUS had been applied but without a change in the proliferation of the HCs. These findings provide evidence in favour of the use of LIPUS in the treatment of fractures.

Surgery for clavicular and humeral fractures in an osteopetrotic patient: a case report.

Osteopetrosis is a rare disease characterised by generalised sclerosis of the bone. Surgical treatment for fractures in osteopetrotic bones is difficult due to their hardness. We report successful surgical treatment of humeral and clavicular fractures in a 30-year-old osteopetrotic patient with severe multiple trauma. Two years after surgery, the patient had a full range of movement at the shoulder and elbow, with good bone union and alignment.

Repair of osteochondral defects with a new porous synthetic polymer scaffold.

We developed a new porous scaffold made from a synthetic polymer, poly(DL-lactide-co-glycolide) (PLG), and evaluated its use in the repair of cartilage. Osteochondral defects made on the femoral trochlear of rabbits were treated by transplantation of the PLG scaffold, examined histologically and compared with an untreated control group. Fibrous tissue was initially organised in an arcade array with poor cellularity at the articular surface of the scaffold. The tissue regenerated to cartilage at the articular surface. In the subchondral area, new bone formed and the scaffold was absorbed. The histological scores were significantly higher in the defects treated by the scaffold than in the control group (p<0.05). Our findings suggest that in an animal model the new porous PLG scaffold is effective for repairing full-thickness osteochondral defects without cultured cells and growth factors.

An in vitro study demonstrating that haematomas found at the site of human fractures contain progenitor cells with multilineage capacity.

We isolated multilineage mesenchymal progenitor cells from haematomas collected from fracture sites. After the haematoma was manually removed from the fracture site it was cut into strips and cultured. Homogenous fibroblastic adherent cells were obtained. Flow cytometry revealed that the adherent cells were consistently positive for mesenchymal stem-cell-related markers CD29, CD44, CD105 and CD166, and were negative for the haemopoietic markers CD14, CD34, CD45 and CD133 similar to bone-marrow-derived mesenchymal stem cells. In the presence of lineage-specific induction factors the adherent cells could differentiate in vitro into osteogenic, chondrogenic and adipogenic cells. Our results indicate that haematomas found at a fracture site contain multilineage mesenchymal progenitor cells and play an important role in bone healing. Our findings imply that to enhance healing the haematoma should not be removed from the fracture site during osteosynthesis.

Change in the cross-sectional area of a patellar tendon graft after anterior cruciate ligament reconstruction.

The purpose of this study was to clarify the change in the cross-sectional area (CSA) of a patellar tendon graft after anterior cruciate ligament (ACL) reconstruction, and its relationship with postoperative knee laxity. Forty patients (25 men and 15 women) were included in this study. Intraoperative CSA measurements were performed with an instrumented areamicrometer, while a magnetic resonance imaging (MRI) evaluation was utilized for the assessment postoperatively. For intraoperative measurement, the average CSA of a 10-mm wide patellar tendon graft was 32.3 +/- 7.0 mm2, while the average CSA measured at follow-up (mean: 14.8 months) was 48.8 mm2, showing a significant mean increase ratio of 49.4%. This value corresponded to 115% of the native ACL. The average CSA measured in 30 patients at 6 months was 49.7 mm2, almost equal to the value at the final follow-up (49.8 mm2) in the same patient group. Among potentially influential factors, postoperative notch width (available space for the ACL graft) had significant correlation with the CSA of the graft at follow-up. Finally, both intra- and postoperative CSA values did not correlate with postoperative knee laxity, indicating that a bigger graft does not guarantee a better laxity.

Treatment of a full-thickness articular cartilage defect in the femoral condyle of an athlete with autologous bone-marrow stromal cells.

OBJECTIVES: Human bone-marrow stromal cells are believed to be multipotent even in adults. This study assessed the effectiveness of autologous bone-marrow stromal cells, which were embedded within a collagen scaffold, to repair a full-thickness articular cartilage defect in the medial femoral condyle of an athlete. PATIENT AND METHODS: A 31-year-old male judo player suffering from pain in the right knee was reviewed. A 20 x 30-mm full-thickness cartilage defect (International Cartilage Repair Society classification (ICRS) grade IV) was revealed in the weight-bearing area of the medial femoral condyle. With the informed consent of the patient, the defect was treated with autologous bone-marrow stromal cells. Bone marrow was aspirated from the iliac crest of the patient 4 weeks before surgery. After removing the erythrocytes, the remaining cells were expanded in culture. Adherent cells were collected and embedded within a collagen gel, which was transferred to the articular cartilage defect in the medial femoral condyle. The implant was covered with an autologous periosteal flap. RESULTS: Seven months after surgery, arthroscopy revealed the defect to be covered with smooth tissues. Histologically, the defect was filled with a hyaline-like type of cartilage tissue which stained positively with Safranin-O. One year after surgery, the clinical symptoms had improved significantly. The patient had reattained his previous activity level and experienced neither pain nor other complications. CONCLUSIONS: Our findings indicate that the transplantation of autologous bone-marrow stromal cells can promote the repair of large focal articular cartilage defects in young, active patients.

Radiculopathy due to microfibrillar collagen hemostat mimicking recurrence of disc herniation.

Microfibrillar collagen hemostat (Avitene) is an absorbable topical hemostatic agent prepared from purified bovine corium collagen. A 65-year-old woman presented with left buttock and lower extremity radicular pain. The patient underwent a disc excision in which Avitene was used to control venous bleeding from the epidural space. Leg pain decreased postoperatively, but she developed radicular pain when she started walking 3 days after the operation. Magnetic resonance imaging (MRI) performed post-operatively showed there was a mass lesion located between the dural sac and L5 nerve root. The lesion exhibited high signal intensity on T1-weighted images and higher signal intensity at the rim of the mass on T2-weighted images. A second operation performed 10 days later revealed that the nerve root was adherent to an extradural granulomatous mass associated with Avitene. Macroscopically, the resected mass was found to be composed mainly of microfibrillar collagen hemostat materials. Hemostat agents may produce a clinically symptomatic, radiologically apparent mass lesion. When considering a mass lesion arising after spine surgery, the differential diagnosis should include foreign body granuloma along with recurrent disc herniation and peridural scar formation.