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.
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.
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.
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.
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.
Steroid-induced osteonecrosis; Osteochodral autograft transplantation; Mosaicplasty; Femoral condyle
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.
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.
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.
We present a case of arthroscopic fixation for bony Bankart lesion using a double-threaded cannulated screw. A 39-year-old man sustained a left shoulder injury from a motorcycle accident. Radiographs showed bony Bankart lesion and CT revealed 40% defect of glenoid articular surface. Arthroscopic fixation was performed using double-threaded cannulated screw after the bony fragment was reduced by suturing the labrum at the edge with a suture anchor. Arthroscopic bony Bankart repair using double-threaded cannulated screw fixation is effective because compression force could be applied between bony fragments and the screw head is not exposed in the glenohumeral joint.
Intervertebral disc tissue homeostasis is modulated by a variety of molecules. Silent mating type information regulator 2 homolog 1 (SIRT1) plays a key role in various physiological processes. The aim of the present study was to verify the expression of SIRT1 and determine SIRT1 function in human intervertebral disc cell homeostasis.
Human nucleus pulposus (NP) cells were obtained from 24 surgical patients (mean age: 39.4 years) and monolayer-cultured. SIRT1 expression was investigated using RT-PCR analysis and immunohistochemical staining. Quantitative real-time RT-PCR was performed to detect mRNA expression of SIRT1 and other genes: aggrecan, collagen type 2 and Sox9. The effect of SIRT1 on the extracellular matrix metabolism of NP cells was examined using recombinant human SIRT1 protein and a protein delivery reagent. Cell number and proliferation activity were measured following SIRT1 treatment. To reveal the deacetylation potential of transfected recombinant human SIRT1, western blotting for acetylated p53 was utilized. R-phycoerythrin was used for the negative control.
SIRT1 expression was confirmed at both mRNA and protein levels in almost all NP cells. Real-time RT-PCR analysis showed SIRT1 mRNA expression significantly increased with donor age (P <0.05, ρ = 0.492). Pfirrmann grade 3 discs showed significantly higher SIRT1 mRNA expression than other grades. SIRT1 treatment significantly reduced aggrecan, Sox9 and collagen type 2 mRNA expression in a dose-dependent manner in all disease classes and disc degeneration grades. Proliferation activity was decreased by SIRT1 treatment in lumbar spinal stenosis and lumbar disc herniation, Pfirrmann grade 3 and grade 4 discs. In contrast, it was significantly upregulated in idiopathic scoliosis, Pfirrmann grade 2 discs. The negative control protein did not affect extracellular matrix metabolism or proliferation activity.
We demonstrate for the first time that SIRT1 is expressed by human NP cells. SIRT1 expression was significantly elevated in an early degeneration stage. SIRT1 affected both extracellular matrix metabolism and proliferation activity; the effect of SIRT1 was altered according to disease class and disc degeneration grade. SIRT1 appears to play a key role in homeostasis during the human intervertebral disc degeneration process.
This study evaluated the application of a layered cell free poly (L-lactic acid) (PLLA) scaffold to regenerate an infraspinatus tendon defect in a rabbit model. We hypothesized that PLLA scaffold without cultivated cells would lead to regeneration of tissue with mechanical properties similar to reattached infraspinatus without tendon defects.
Layered PLLA fabric with a smooth surface on one side and a pile-finished surface on the other side was used. Novel form of layered PLLA scaffold was created by superimposing 2 PLLA fabrics. Defects of the infraspinatus tendon were created in 32 rabbits and the PLLA scaffolds were transplanted, four rabbits were used as normal control. Contralateral infraspinatus tendons were reattached to humeral head without scaffold implantation. Histological and mechanical evaluations were performed at 4, 8, and 16 weeks after operation.
At 4 weeks postoperatively, cell migration was observed in the interstice of the PLLA fibers. Regenerated tissue was directly connected to the bone composed mainly of type III collagen, at 16 weeks postoperatively. The ultimate failure load increased in a time-dependent manner and no statistical difference was seen between normal infraspinatus tendon and scaffold group at 8 and 16 weeks postoperatively. There were no differences between scaffold group and reattach group at each time of point. The stiffness did not improve significantly in both groups.
A novel form of layered PLLA scaffold has the potential to induce cell migration into the scaffold and to bridge the tendon defect with mechanical properties similar to reattached infraspinatus tendon model.
A successful scaffold for use in tendon tissue engineering requires a high affinity for living organisms and the ability to maintain its mechanical strength until maturation of the regenerated tissue. We compared two types of poly(L-lactic acid) (PLLA) scaffolds for use in tendon regeneration, a plain-woven PLLA fabric (fabric P) with a smooth surface only and a double layered PLLA fabric (fabric D) with a smooth surface on one side and a rough (pile-finished) surface on the other side. These two types of fabric were implanted into the back muscles of rabbits and evaluated at three and six weeks after implantation. Histological examination showed collagen tissues were highly regenerated on the rough surface of fabric D. On the other hand, liner cell attachment was seen in the smooth surface of fabric P and fabric D. The total DNA amount was significantly higher in fabric D. Additionally, mechanical examination showed fabric P had lost its mechanical strength by six weeks after implantation, while the strength of fabric D was maintained. Fabric D had more cell migration on one side and less cell adhesion on the other side and maintained its initial strength. Thus, a novel form of double-layered PLLA fabric has the potential to be used as a scaffold in tendon regeneration.
Osteoarthritis of the talonavicular joint caused by inflammatory, degenerative, and post-traumatic arthritis has been commonly described, and isolated arthrodesis for talonavicular joint has usually been performed for such conditions. However, arthritis accompanied by pseudarthrosis of the navicular bone is an extremely rare case, and to the best of our knowledge, isolated arthrodesis for this situation has not been previously described in any published reports.
The patient was a 39-year-old Japanese man. He had complained of pain in his left middle foot since a fall from his motorcycle six months previously. Radiographs and computed tomography (CT) scans revealed pseudarthrosis of the navicular bone. MRI indicated mild arthritic change in the talonavicular joint and avascular necrosis of the navicular bone. We performed an isolated arthrodesis of the talonavicular joint with two 6.5 mm cancellous screws. One year after the operation, radiographical bone union had been obtained, and the patient reported no pain and complete satisfaction with the result.
Isolated talonavicular arthrodesis is one of the effective procedures for the treatment of traumatic talonavicular arthritis with pseudarthrosis of the navicular bone both in providing pain relief and functional improvement.
Carbon dioxide (CO2) therapy refers to the transcutaneous administration of CO2 for therapeutic purposes. This effect has been explained by an increase in the pressure of O2 in tissues known as the Bohr effect. However, there have been no reports investigating the oxygen dissociation of haemoglobin (Hb) during transcutaneous application of CO2 in vivo. In this study, we investigate whether the Bohr effect is caused by transcutaneous application of CO2 in human living body.
We used a novel system for transcutaneous application of CO2 using pure CO2 gas, hydrogel, and a plastic adaptor. The validity of the CO2 hydrogel was confirmed in vitro using a measuring device for transcutaneous CO2 absorption using rat skin. Next, we measured the pH change in the human triceps surae muscle during transcutaneous application of CO2 using phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in vivo. In addition, oxy- and deoxy-Hb concentrations were measured with near-infrared spectroscopy in the human arm with occulted blood flow to investigate O2 dissociation from Hb caused by transcutaneous application of CO2.
The rat skin experiment showed that CO2 hydrogel enhanced CO2 gas permeation through the rat skin. The intracellular pH of the triceps surae muscle decreased significantly 10 min. after transcutaneous application of CO2. The NIRS data show the oxy-Hb concentration decreased significantly 4 min. after CO2 application, and deoxy-Hb concentration increased significantly 2 min. after CO2 application in the CO2-applied group compared to the control group. Oxy-Hb concentration significantly decreased while deoxy-Hb concentration significantly increased after transcutaneous CO2 application.
Our novel transcutaneous CO2 application facilitated an O2 dissociation from Hb in the human body, thus providing evidence of the Bohr effect in vivo.
Osteochondrosis of the second or third metatarsal head is a rare condition called Freiberg's disease. To relieve foot pain, conservative treatment with a foot orthosis to reduce weight-bearing and immobilize the foot are recommended. In cases in which such treatments have proved to be ineffective, several surgical treatments have been performed. The appropriate surgical treatment for Freiberg's disease remains controversial.
We describe the case of a 20-year-old Japanese woman with a three-year history of right forefoot pain and no history of trauma. Two years after treatment by autologous osteochondral plug transplantation, she has neither complaints nor symptoms.
Autologous osteochondral plug transplantation represents a potentially successful surgical arthroplastic option in preserving the metatarsophalangeal joint in patients with Freiberg's disease.
Autologous chondrocyte implantation (ACI) is considered a promising choice for the treatment of cartilage defects. However, the application of ACI to osteoarthritic patients is, in general, contraindicated. The purpose of this study is to evaluate the efficiency of three-dimensionallystructured ACI (3D-ACI; CaReS) in a rat model of knee osteoarthritis (OA).
OA-like degenerative changes in the articular cartilage were created by transecting the anterior cruciate ligament (ACLT) in athymic nude rats. Two weeks later, CaReS was transplanted at the cartilage injury sites created by micro-drilling in the patella groove (Chondrocyte-implanted (CI) group: CaReS collagen with human chondrocytes; Collagen group: CaReS collagen without cells; and Sham group: sham operation; n = 15/group).
Reverse Transcription Polymerase Chain Reaction (RT-PCR) analysis demonstrated the expression of human-specific type 2 collagen and Sry-type high-mobility-group box 9 (SOX9) in the CI group—not in the other groups—throughout the study period. Double immunohistochemistry for human-specific type 2 collagen and human leukocyte antigen-abacavir (HLA-ABC) at week 4 showed positive staining in the CI group only. Macroscopic assessment showed better repair at the cartilage defect sites in the CI group, compared to the other groups. Histological assessment with toluidine blue staining showed that the thickness of the articular cartilage and semi-quantitative histological scores were higher in the CI group than in the other groups up to week 20.
We demonstrate, for the first time, that 3D-ACI is effective in repairing cartilage defects in a rat model of ACLT-induced OA.
Chondrocyte implantation; geriatrics; knee osteoarthritis; orthopedics
The therapeutic potential of hematopoietic stem cells/endothelial progenitor cells (HSCs/EPCs) for fracture healing has been demonstrated with evidence for enhanced vasculogenesis/angiogenesis and osteogenesis at the site of fracture. The adaptor protein Lnk has recently been identified as an essential inhibitor of stem cell factor (SCF)–cKit signaling during stem cell self-renewal, and Lnk-deficient mice demonstrate enhanced hematopoietic reconstitution. In this study, we investigated whether the loss of Lnk signaling enhances the regenerative response during fracture healing. Radiological and histological examination showed accelerated fracture healing and remodeling in Lnk-deficient mice compared with wild-type mice. Molecular, physiological, and morphological approaches showed that vasculogenesis/angiogenesis and osteogenesis were promoted in Lnk-deficient mice by the mobilization and recruitment of HSCs/EPCs via activation of the SCF–cKit signaling pathway in the perifracture zone, which established a favorable environment for bone healing and remodeling. In addition, osteoblasts (OBs) from Lnk-deficient mice had a greater potential for terminal differentiation in response to SCF–cKit signaling in vitro. These findings suggest that inhibition of Lnk may have therapeutic potential by promoting an environment conducive to vasculogenesis/angiogenesis and osteogenesis and by facilitating OB terminal differentiation, leading to enhanced fracture healing.
Nodular fasciitis is a rapidly growing mass, with high cellularity and mitotic activity, that can be both clinically and histologically misdiagnosed as a soft tissue sarcoma. Nodular fasciitis of the hand is an extremely rare condition. We report a 17-year-old male hand-ball player with nodular fasciitis in the dominant hand. The patient presented with a rapidly growing mass in his right hand and no history of major trauma. On physical examination, a painful mass measuring 2 cm in diameter was observed in the first web space. Magnetic resonance imaging (MRI) demonstrated a subcutaneous mass with isointensity on T1-weighted images and inhomogeneous high intensity on T2-weighted images. The lesion was inhomogeneously enhanced after intravenous administration of gadolinium. Moreover, thallium-201 scintigraphy showed high uptake at the early phase and no wash-out at the delayed phase. We performed an excisional biopsy. The mass was present subcutaneously and adhered to the interosseous muscle fascia. Although a pathological examination by frozen section during surgery showed a low-grade spindle cell sarcoma, the final histological diagnosis was nodular fasciitis. There was no evidence of local recurrence at the recent follow-up 2 years after the operation. We speculate that repeated small injuries as a result of sports activities played an important causative role in the nodular fasciitis.
Hand; hand-ball player; nodular fasciitis
A case of bilateral pedicle stress fracture of L4 in a patient with osteoporotic compression fracture of L5 and without a history of major trauma or surgery is reported, and the literature is reviewed. Bilateral pedicle fracture is a rare entity and few cases have been reported in the literature. All reported cases had some underlying causative factors like previous spine surgery or stress related activities. To the best of the authors’ knowledge, only one case of bilateral pedicle stress fracture without a history of trauma, previous spine surgery, or stress-related activities has been reported. A 77-year-old woman presented with severe low back pain and radiating pain in the right leg that was exacerbated after standing and walking. Plain radiograph showed pathological fracture at L5 level. Magnetic resonance imaging (MRI) revealed the compression of dural sac at L5 level. CT scan taken 3 months after admission revealed bilateral pedicle fractures through L4. The patient was treated with decompressive laminectomies of L4, followed by posterior spinal fusion with rigid pedicle screw fixation and autogenous bone graft mixed with hydroxyapatite. The patient achieved pain relief and returned to normal activity. Stress fracture of the pedicle within the proximal vertebra of an osteoporotic compression fracture of lumbar spine is an uncommon entity. It may, however, be an additional source of symptoms in patients with osteoporosis who present with further back pain. Surgeons caring for this group of patients should be aware of this condition.
Pedicle fracture; Stress fracture; Osteoporosis; Low back pain; Lumbar spine
Pneumocephalus is a well-known condition following head trauma, but is rare as an injury or as a result of surgery of the spine. We present a 76-year-old patient with a rare case of pneumocephalus associated with a cerebrospinal fluid fistula as a complication of surgical treatment for cervical myelopathy. Although cerebrospinal fluid leakage was noted and the injured dura was carefully sutured at operation, tension pneumocephalus occurred. The resultant pneumocephalus was diagnosed based on neurogenic symptoms including sudden convulsion, head radiograph, and computed tomography scan. The benign course of the pneumocephalus postdiagnosis did not require secondary operation.
We have made three types of poly (DL-lactide-co-glycolide) (PLG) scaffolds (porosity: scaffold I 80 ± 0.9%, II 85 ± 0.8%, III 92 ± 0.7%; compression module determined with 10% strain: scaffold I 0.26 MPa, II 0.091 MPa, III 0.0047 MPa). Osteochondral defects made in the femoral condyle of rabbits were treated with these scaffolds and the possibilities of cartilage repair were investigated histologically. At post-operative weeks 6 and 12, histological scores in the groups of scaffolds II and III were significantly higher than the score in the group of scaffold I. Scaffolds II and III, which have higher porosity than scaffold I, allow better migration of bone marrow cells and better replacement of the scaffold with bone and cartilage than scaffold I. This study suggests that higher porosity allowing bone marrow cells to migrate to the scaffold is important in repairing osteochondral defects.
Patients with neurosarcoidosis are usually initially treated with steroid administration even when they have concomitant cord compression on magnetic resonance imaging (MRI). Operative intervention may be indicated in patients with spinal cord sarcoidosis requiring either tissue biopsy for diagnosis or associated with progressive neurologic symptoms. However, there have been no previous reports describing clinical outcomes of laminoplasty for spinal cord sarcoidosis. The objectives of this study are to investigate whether extensive cervical laminoplasty is an effective treatment for spinal cord sarcoidosis combined with spondylotic changes and/or cervical spinal canal stenosis. Open-door laminoplasty was performed in three patients with spinal cord sarcoidosis. All patients received intensive corticosteroid therapy after the operation MRI imaging was performed in all patients before and after the operation. Operative outcomes were not satisfactory and the clinical courses of the patients fluctuated after corticosteroid therapy. Daily life activities were not significantly improved after treatments in any of the three patients, and in the long-term follow-up period the clinical course of one patient was one of inexorable deterioration to a state of quadriplegia. The possibility of spinal cord sarcoidosis should be included in the differential diagnosis, when a distinct high signal intensity area is observed within the spinal cord on T2-weighted MR images in patients with spondylotic changes. Laminoplasty is not an effective intervention for the treatment of spinal cord sarcoidosis even when patients have spondylotic changes and/or a constitutionally narrowing cervical spinal canal. Patients with neurosarcoidosis should be treated first with steroid administration even when they have concomitant cord compression on MRI.
Sarcoidosis; Spinal cord; Cervical spine; Laminoplasty; Spondylosis
RNA interference (RNAi) technology has recently emerged as an important biological strategy for gene silencing. Previously, the efficacies of RNAi in cultured nucleus pulposus cells in vitro have been reported. However, RNAi in the disc in vivo has never been reported. Therefore, the aims of the present study were to establish a method for RNAi in the disc in vivo and to evaluate the applicability of this technique for endogenous genes in the intervertebral discs using Fas Ligand (FasL) as a representative endogenous gene. To evaluate the efficacy of RNAi in vivo, two reporter luciferase plasmids (Firefly and Renilla) were used. These plasmids and unmodified short interference RNA (siRNA) duplex for targeting Firefly luciferase were co-transfected into coccygeal intervertebral disc of Sprague-Dawley rats in vivo using the ultrasound gene transfer technique. To evaluate the RNAi of the endogenous gene in vivo, siRNAs targeting rat FasL were transfected with the same technique. Non-specific siRNA was used as the negative control. The discs receiving no siRNAs were used as the control. The inhibitory effect of Firefly luciferase against Renilla luciferase was obtained using the results of dual-luciferase assay. Down-regulation of endogenous FasL was calculated by the data from real-time PCR. Our results showed that siRNA for Firefly luciferase can dramatically down-regulate the Firefly luciferase gene expression in vivo compared with Renilla luciferase. The inhibitory effects were maintained for at least 24 weeks and at 24 weeks post transfection, the inhibitory rate was 80% compared with the control group. Furthermore, the siRNA co-transfection group inhibited endogenous FasL expression by 53% compared with the control group. The present study demonstrates long-term down-regulation mediated by unmodified siRNA is possible not only for the exogenous reporter gene, but also for endogenous FasL expression in rat discs in vivo. This application of RNAi might be promising as a local therapy for disc degeneration and associated disorders by down-regulating some of the genes that are harmful for the normal physiology of the disc and may cause disc degeneration.
RNA interference (RNAi); Unmodified siRNA; Intervertebral disc; Animal model; Ultrasound gene therapy
In this study, we performed a mechanical analysis of the effect of fibroblast growth factor-2 (FGF-2) on autologous osteochondral transplantation in a rabbit model. A full-thickness cartilage defect (diameter: 5 mm; depth: 5 mm) made in the right femoral condyle was treated with osteochondral transplantation using an osteochondral plug (diameter: 6 mm; depth: 5 mm) taken from the left femoral condyle. The animals were divided into three groups: Group I, the defect was filled with 0.1 ml of gelatin hydrogel containing 1 μg of FGF-2; Group II, the defect was filled with 0.1 ml of gelatin hydrogel only; Group III, the defect was left untreated. Thereafter, osteochondral plugs were transplanted and the transplanted osteochondral grafts were evaluated mechanically and histologically at postoperative weeks 1, 3, 8 and 12. The structural property of the osteochondral graft was significantly greater in Group I than in Groups II and III at postoperative week 3. Histological analysis at 3 weeks revealed a tendency towards increased subchondral bone trabeculae in Group I compared with the other groups. Autologous osteochondral grafts transplanted with gelatin hydrogel containing FGF-2 acquired adequate stiffness at an early postoperative phase.