Expression of proinflammatory cytokines and proinsulin by bone marrow-derived cells for fracture healing in long-term diabetic mice.

BACKGROUND: Diabetes mellitus (DM) causes bone dysfunction due to poor bone quality, leading to severe deterioration in patient of quality of life. The mechanisms of bone metabolism in DM remain unclear, although chemical and/or mechanical factors are known to disrupt the homeostasis of osteoblasts and osteoclasts. The purpose of this study was to identify the changes of osteoblasts and osteoclasts under long-term hyperglycaemic conditions, using a mouse fracture model of long-term hyperglycemia (LT-HG). METHODS: C57BL/6J mice and green fluorescent protein (GFP) -positive bone marrow transplanted C57BL/6J mice with LT-HG, maintained under a state of hyperglycaemia for 2 months, were used in this study. After the experimental fracture, we examined the immunohistochemical expression of proinsulin and tumor necrosis factor (TNF) -α at the fracture site. C57BL/6J fracture model mice without hyperglycaemia were used as controls. RESULTS: In the LT-HG mice, chondrocyte resorption was delayed, and osteoblasts showed an irregular arrangement at the callus site. The osteoclasts were scattered with a decrement in the number of nuclei. The expression of proinsulin was confirmed in bone marrow derived cells (BMDCs) with neovascularization 2 and 3 weeks after fracture. Immunopositivity for TNF-α was also confirmed in immature chondrocytes and BMDCs with neovascularization at 2 weeks, and the number of positive cells was not decreased at 3 weeks. Examination of GFP-grafted hyperglycaemic mice showed that the majority of cells at the fracture site were GFP-positive. Immunohistochemistry showed that the rate of double positives was 15% for GFP and proinsulin and 47% for GFP and TNF-α. CONCLUSION: LT-HG induces an increase in the number of proinsulin and TNF-α positive cells derived from BMDCs. We suggest that proinsulin and TNF-α positive cells are involved in both bone formation and bone resorption after fracture under hyperglycaemic conditions, resulting in the delay of bone healing.

Consideration of differences in drug usage between young-onset and elderly-onset rheumatoid arthritis with target of low disease activity.

OBJECTIVES: Elderly-onset rheumatoid arthritis (EORA) is reported to differ from young-onset rheumatoid arthritis (YORA) with regard to patient background and drug treatment. We examined the amount of drug administered to patients who achieved low disease activity (LDA) for rheumatoid arthritis at our hospital. METHODS: Demographics, clinical history, and treatments were compared between patients with EORA (n = 70) and YORA (n = 190). RESULTS: There was a significant difference in the average age (73.8 vs. 57.8 years), disease duration (6.66 vs. 14.7 years), and sex (62.9% males vs. 83.7% females), but no difference in rheumatoid factor positivity (85.3% vs. 80.7%), anti-citrullinated peptide antibody positivity (86.5% vs. 87.7%), simplified disease activity index (4.28 vs. 4.59), or disease activity score 28-CRP (1.99 vs. 2.04) in the EORA and YORA groups, respectively. There were also no significant differences in prednisolone use (37.1% vs. 36.3%), amount of methotrexate administered (MTX) (1.45 vs. 1.41 mg), and MTX use (55.7% vs. 65.3%). However, the MTX dose (2.89 vs. 4.09 mg/week, p = .011) and overall biologics use (32.9% vs. 56.3%, p = .0012) were significantly lower in patients with EORA than in those with YORA. CONCLUSION: Patients with EORA may be able to achieve LDA with lower drug dosage than those with YORA.

ß-Angles of hips with femoroacetabular impingement versus asymptomatic normal hips in a Japanese population: A CT-based observational clinical study.

BACKGROUND: The beta angle (ß-angle)-although used to assess femoroacetabular impingement (FAI)-has not been well evaluated. This study aimed to measure the ß-angle on multiradial computed tomography (CT) slice images of both hips with symptomatic FAI and asymptomatic normal hips to determine its optimal cutoff value for detecting FAI in a Japanese population. METHODS: CT was performed with each subject supine. The ß-angle was measured on seven radial slices (designated R0, R15, R30, R45, R60, R75, R90) that were generated at 15° intervals from the oblique axial slice through the center of the femoral neck. An a priori power analysis was performed. The measurements were made in 20 FAI hips (FAI group) and 23 asymptomatic normal hips (ANH group). Cutoff values were evaluated using receiver operating characteristic curves. RESULTS: The mean ß-angles of the FAI and ANH groups at R0, R15, R30, R45, R60, R75, and R90° were, respectively, 73.6° and 84.2°, 66.0° and 79.3°, 57.2° and 69.2°, 48.1° and 63.1°, 46.7° and 62.5°, 50.0° and 63.7°, and 53.7° and 65.9°. For all slices, the ß-angle was significantly smaller in the FAI group than the ANH group. The optimal ß-angle cutoff values for diagnosing FAI at R0, R15, R30, R45, R60, R75, and R90 were 73.9°, 70.2°, 61.4°, 55.7°, 53.6°, 59.4°, and 60.9°, respectively. The respective specificities and sensitivities of the cutoff values at R0, R15, R30, R45, R60, R75, and R90 were 78.3% and 65.0%, 82.6% and 70.0%, 73.9% and 60.0%, 73.9% and 75.0%, 95.7% and 75.0%, 69.6% and 95.0%, and 78.3% and 80.0%. CONCLUSIONS: In all radial slices, the ß-angle was significantly smaller in the hips with symptomatic FAI than in the asymptomatic normal hips. The most useful cutoff value for diagnosing FAI was a ß-angle of 53.6° at R60.

Aortic pulsation prevents the development of ossification of anterior longitudinal ligament toward the aorta in patients with diffuse idiopathic skeletal hyperostosis (DISH) in Japanese: Results of chest CT-based cross-sectional study.

BACKGROUND: The development and etiology of diffuse idiopathic skeletal hyperostosis (DISH) were far from complete understanding. Even the precise mechanism of the development of its typical right-sided ossification of the anterior longitudinal ligament (OALL) frequently compared to 'flowing candle wax', a hallmark of DISH, remains unknown. METHODS: The participants of this study were 261 individuals (31 females and 230 males) diagnosed as DISH according to the criteria established by Resnick and Niwayama extracted from a consecutive 3013 patients who have undergone chest CT for the examination of pulmonary diseases in our institute. The patients with previous thoracic spine surgery and younger than 15 years old were excluded. Chest CT data were converted to the condition suitable for bone evaluation by the software application. The positional relationship between thoracic aorta and OALL, the morphology of the OALL adjacent to the aorta and the presence of calcification of the aortic wall adjacent to the OALL were studied. RESULTS: Of 261 individuals with DISH, we found that thoracic aorta was localized adjacent to the OALL (AD-group) in 123 cases (47%), whereas 138 cases (53%) were not (NAD-group). All OALL in AD-group was localized between T6 and T12. The shape of the OALL adjacent to the aorta was either flat or concave except for one. No case showed obvious calcification of the aortic wall adjacent to the OALL in AD-group. CONCLUSIONS: The aortic pulsation might play an important role in inhibit the development of the OALL toward the aorta in DISH. It is likely that establishment of the optimal condition of the pulsation stress simulating aortic pulsation and its delivery system can achieve arresting, slowing the progression and/or changing the morphology of the ossified lesions.

Wnt signaling pathway correlates with ossification of the spinal ligament: A microRNA array and immunohistochemical study.

BACKGROUND: Ossification of the posterior longitudinal ligament or the ligamentum flavum parallels endochondral ossification. Cell differentiation at the ossification front is known to be important during this process, although the factors regulating its initiation and progression are still unclear. The purpose of this study was to identify factors important for the regulation of chondrocyte/osteoblast differentiation during spinal ossification. METHODS: Ligamentum flavum tissue was isolated from 25 patients who underwent decompressive surgery for cervical ossification of the posterior longitudinal ligament. Tissue sections were used for in vitro culture to obtain primary cells through migration methods. To identify microRNAs associated with ossification of the posterior longitudinal ligament, cultured cells were prepared from the ligamentous tissue (n = 4; continuous type) or from control ligamentous samples harvested from patients with cervical spondylosis without spinal ossification, and analyzed using a microRNA array. The ligamentous sections were also examined by immunohistochemistry for the expression of candidate microRNA target genes. RESULTS: The microRNA array identified 177 factors; 12 of which were expressed at significantly different levels in patients with ossification of the posterior longitudinal ligament compared to those in control patients. The hsa-miR-487b-3p was down-regulated in patients with ossification of the posterior longitudinal ligament, which met the false discovery rate of <0.05. This microRNA was predicted to regulate the expression of genes involved in Wnt signaling. Furthermore, immunohistochemistry of Wnt signaling proteins, including Wnt 3a, LRP5/6, and beta-catenin, revealed positive expression in mesenchymal cells and/or premature chondrocytes at the ossification front. CONCLUSION: Our results suggested that down-regulation of miR-487b-3p plays an important role in the initiation of Wnt signaling during the ossification process. Wnt signaling may regulate both chondrocyte and osteoblast differentiation and the specification of endochondral ossification in the pathogenesis of ossification of the posterior longitudinal ligament or the ligamentum flavum.

Knee joint synovial hemangioma treated with arthroscopic resection without hemarthrosis: A case report.

INTRODUCTION: Intra-articular synovial hemangioma of the knee is a relatively rare benign tumor that if left undiagnosed and treated may be followed by degenerative cartilaginous changes and osteoarthritis. However, the non-specific symptoms of synovial hemangiomas limit its early diagnosis. We report our encounter with synovial hemangioma of the knee in which the diagnosis was based on a > 20-year history of chronic pain without joint swelling or hematoma. PRESENTATION OF CASE: A 34-year-old man with a localized vascular malformation on the upper edge of the left patella presented with pain and a restricted range of motion. CT and MRI revealed a tumorous lesion at this location. Upon excision of the lesion, the patient's symptoms disappeared, with no recurrence at the 1-year follow-up. DISCUSSION: Accurate diagnosis and appropriate early treatment are necessary for synovial hemangiomas to forestall articular cartilage degeneration due to recurrent intra-articular hemorrhages. CONCLUSION: Synovial hemangioma should be considered when a patient presents with recurrent knee pain, even in the absence of swelling or episodes of joint effusion.

Modified metaphyseal-loading anterolaterally flared anatomic femoral stem: five- to nine-year prospective follow-up evaluation and results of three-dimensional finite element analysis.

We have designed a proximal-fitting, anterolaterally flared, arc-deposit hydroxyapatite-coated anatomical femoral stem (FMS-anatomic stem; KYOCERA Medical, Osaka, Japan) for cementless total hip arthroplasty (THA) for Japanese patients with dysplastic hip osteoarthritis, using a nonlinear three-dimensional finite element analysis simulating loading conditions. The Anatomic Fit stem was modified in the region of the arc-sprayed surface, to allow more proximal appearance of spot welds. The aim of the present study was to analyze the clinical and radiographic outcomes of patients who underwent THA using this stem. We reviewed 73 consecutive patients (79 hips; 13 men 16 hips; 60 women 63 hips; age at surgery, 57.6 years, range, 35-78) who underwent cementless THA using the Anatomic Fit stem, at a follow-up period of 7.1 years (range, 5.1-9.4). Harris Hip score improved from 40.7 ± 17.1 before surgery to 91.0 ± 5.2 points at follow-up. The 7.1-year stem survival rate was 100%. Radiographs at follow-up confirmed the stability of the femoral stems within the femoral canal in all cases, with sufficient bone ingrowth. None of the patients had subsidence of the stem exceeding 2.0 mm within the femoral canal or changes in varus or valgus position of more than 2.0°. The Anatomic Fit stem provided excellent results. The nonlinear three-dimensional finite element analysis demonstrated that the stem-bone relative motion was 10 µm at the proximal end of the stem and proximal load transfer. Our analysis confirmed reduced radiolucency around the stem, minimal subsidence, appropriate stress shielding, and promising medium-term stability within the femoral canal.

Dislocated intra-articular femoral head fracture associated with fracture-dislocation of the hip and acetabulum: report of 12 cases and technical notes on surgical intervention.

This report describes case series of the femoral head fractures associated with fracture-dislocation of the hip joint to evaluate the mid- and long-term outcomes and to highlight the surgical technique of fixation of the femoral head from the posterior trochanteric flip osteotomy approach. Twelve patients (6 men and 6 women) with dislocated femoral head fractures (mean age at the time of injury, 56 years; range, 23-80) were followed up for mean period of 9.7 years (range, 5-20). All dislocations were reduced within less than 6 h after the injury. The type of femoral head fracture was classified according to the Pipkin classification on radiographs and CT. Five patients were classified as type I, 2 as type II, 2 as type III, and 3 as type IV. The clinical and radiological outcomes were assessed by Thompson and Epstein's regimen. Excluding 2 patients with Pipkin type III, the outcome of 9 patients was excellent/good, and poor in 1. The latter patient sustained Pipkin type IV and developed osteoarthritis 1 year after surgery and consequently required total hip arthroplasty. We conclude that small fragment of the femoral head less than 1 cm can be removed, while larger fragments should be fixed by bioabsorbable screws or pins in all types of femoral head fractures. In Pipkin type IV fractures, surgeons should always take anatomical reduction in the acetabulum into consideration during surgery.

Fracture of the acetabulum: a retrospective review of ninety-one patients treated at a single institution.

Acetabular fracture result in fairly good outcome after the anatomic reduction in the displaced fracture fragments and damaged joint structure, but some patients will inevitably suffer from hip joint problems during their courses after the insult. We retrospectively reviewed 91 patients with acetabular fractures to investigate the causes of clinical failure and relationship among the fracture types, selected treatment options and their courses. Ninety-one patients (73 men and 18 women) with an average age of 49 years (range 18-80) at the time of injury were followed up for an average of 8.6 years (range 2-18). Judet-Letournel classification of fracture type and Matta's rating regimen of functional and radiographic patient' assessment were conducted. Conservative treatment was provided in 20 patients, in which 19 attained excellent/good, and one fair clinical results. All achieved excellent/good radiographic outcome. Surgically treated patients (n = 71) with critical dislodgement of the fracture fragment showed that 64 (90%) attained excellent/good and 7 (10%) fair/poor clinical outcomes. Sixty-three (89%) attained excellent/good and 8 (11%) fair/poor postoperative radiographic outcome. Five patients with poor radiographic outcome after surgery subsequently required total hip arthroplasty, due to the development of hip joint osteoarthritis in 3 and femoral head avascular necrosis in 2. We conclude that displacement of the joint surface should be reduced to less than 3 mm in accordance with the selection of the most appropriate surgical approach for open reduction/fixation in each fracture type; however, comminuted fracture and avascular necrosis of the femoral head may be the cause of poor clinical results.

Increased Cellular Expression of Interleukin-6 in Patients With Ossification of the Posterior Longitudinal Ligament.

STUDY DESIGN: We performed histologic, immunohistochemical, immunoblot examination and suspension array analyses of cytokine expression in cultured cells derived from human cervical ossification of the posterior longitudinal ligament (OPLL). OBJECTIVE: To determine the roles of interleukin-6 (IL-6) during the maturation of osteoblasts and chondrocytes associated with the development of OPLL. SUMMARY OF BACKGROUND DATA: Ectopic OPLL affects ~3% of the general population, with a higher incidence in Asian ethnic groups. Alterations in cytokine profiles may influence osteoblast differentiation, but the mechanisms and signaling pathways associated with the ossification process remain unclear. METHODS: Samples were collected from 14 patients with OPLL who had undergone spinal surgery and seven with cervical spondylotic myelopathy without OPLL. Tissue sections were used for histologic and immunohistochemical studies, and primary cells from ligamentum samples were used for cytokine array and immunoblotting. A suspension array was used to measure the concentrations of 27 inflammatory cytokines or growth factors. RESULTS: Suspension array and immunoblot analyses revealed significantly elevated levels of IL-6 in OPLL patients. Alterations in IL-6 concentrations were found to alter the expression of the genes Sox9 , Runx2 , and SIRT1 . In addition, immunohistochemical analysis revealed that these factors are present in mesenchymal cells within the degenerative portion of the ligament matrix that is adjacent to the ossification front. CONCLUSIONS: IL-6 plays a profound role in the osteoblast differentiation process along with the induction of chondrocyte hypertrophy and cell apoptosis in the early stages of ossification in OPLL. These changes in cytokine profiles are essential factors for regulation of the ectopic ossified plaque in OPLL.

Onset of Chronic Expanding Hematoma 25 Years After Total Hip Arthroplasty.

Chronic expanding hematoma (CEH) is a rare anatomical condition that gradually expands due to trauma or surgery. We report the case of a 56-year-old woman who developed CEH 25 years after metal-on-polyethylene total hip arthroplasty. She presented with swelling and radiating pain in the right inguinal region. Tocilizumab was administered for treating rheumatoid arthritis and renal amyloid A amyloidosis. Diagnostic imaging and partial resection revealed a soft tissue mass and a CEH, respectively. The symptoms recurred 6 months later; dialysis was initiated, and the CEH was resected under general anesthesia, leading to improvement. This case report emphasizes the importance of prompt diagnosis and intervention in CEH management for preventing further complications and improving the patient's quality of life.

Changes in gait pattern and hip muscle strength after open reduction and internal fixation of acetabular fracture.

OBJECTIVES: To characterize changes in the gait pattern at 3 and 12 months after surgery for acetabular fracture, to assess the relationship between various gait parameters and hip muscle strength, and to determine the factors associated with gait disorders that correlate with gait parameters measured at 12 months after surgery. DESIGN: Prospective cohort study. SETTING: University hospital. PARTICIPANTS: Patients (N=19) with acetabular fractures were treated by open reduction and internal fixation (ORIF) and examined at 3 and 12 months postoperatively. The study also included a similar number of sex- and age-matched control subjects. INTERVENTIONS: Postoperative rehabilitation program. MAIN OUTCOME MEASURES: Spatiotemporal, kinematic, and kinetic variables of gait and strength of hip flexor, adductor, and abductor muscles at 3 and 12 months after ORIF. RESULTS: Walking velocity at 3 months after ORIF was slower in the patients than in the control subjects; however, walking velocity at 12 months was similar in the 2 groups. Although most of the kinematic and kinetic variables showed recovery to control levels at 3 and 12 months after ORIF, recovery was incomplete for pelvic forward tilt and hip abduction moment even at 12 months after ORIF. The greatest loss of muscle strength was noted in the hip abductors, where the average deficit was 35.4% at 3 months and 24.6% at 12 months. There was a significant relationship between hip abductor muscle strength and hip abduction moment at 3 months (R(2)=.63); however, this relationship diminished at 12 months (R(2)=.14). The presence of associated injuries correlated with lack of recovery of the peak hip abduction moment. CONCLUSIONS: Pelvic forward tilt and peak hip abduction moment showed incomplete recovery at 12 months after ORIF with subsequent conventional and home exercise rehabilitation programs. Our results suggest that improvement of hip abductor muscle strength in the early postoperative period could improve the peak hip abduction moment.

Initiation and progression of ossification of the posterior longitudinal ligament of the cervical spine in the hereditary spinal hyperostotic mouse (twy/twy).

INTRODUCTION: Ossification of the posterior longitudinal ligament (OPLL) is a significantly critical pathology that can eventually cause serious myelopathy. Ossification commences in the vertebral posterior longitudinal ligaments, and intensifies and spreads with the progression of the disease, resulting in osseous projections and compression of the spinal cord. However, the paucity of histological studies the underlying mechanisms of calcification and ossification processes remain obscure. The pathological process could be simulated in the ossifying process of the ligament in mutant spinal hyperostotic mouse (twy/twy). The aim of this study is to observe that enlargement of the nucleus pulposus followed by herniation, disruption and regenerative proliferation of annulus fibrosus cartilaginous tissues participated in the initiation of ossification of the posterior longitudinal ligament of twy/twy mice. MATERIALS AND METHODS: The mutant twy/twy mice (6 to 22-week-old) were used in the present study. The vertebral column was analyzed histologically and immunohistochemically. RESULTS: We observed that the enlargement of the nucleus pulposus followed by herniation, disruption and regenerative proliferation of annulus fibrosus cartilaginous tissues participated in the initiation of ossification of posterior longitudinal ligament of twy/twy mice. In this regards, the cells of the protruded hyperplastic annulus fibrosus invaded the longitudinal ligaments and induced neovascularization and metaplasia of primitive mesenchymal cells to osteoblasts in the spinal ligaments of twy/twy mice. CONCLUSION: Since genetic mechanisms could play a role in human OPLL, the age-related enlargement of the nucleus pulposus in the twy/twy mouse may primarily occur as a result of overproduction of mucopolysaccharide matrix material induced by certain genetic abnormalities.

Apoptosis of neurons and oligodendrocytes in the spinal cord of spinal hyperostotic mouse (twy/twy): possible pathomechanism of human cervical compressive myelopathy.

INTRODUCTION: Cervical compressive myelopathy is the most serious complication of cervical spondylosis or ossification of the posterior longitudinal ligament (OPLL) and the most frequent cause of spinal cord dysfunction. There is little information on the exact pathophysiological mechanism responsible for the progressive loss of neural tissue in the spinal cord of such patients. In this study, we used the spinal hyperostotic mouse (twy/twy) as a suitable model of human spondylosis, and OPLL to investigate the cellular and molecular changes in the spinal cord. Mutant twy/twy mouse developed ossification of the ligamentum flavum at C2-C3 and exhibited progressive paralysis. MATERIALS AND METHODS: The mutant twy/twy mice, aged 16 and 24 weeks, were used in the present study. The cervical spinal cord was analyzed histologically and immunohistochemically. RESULTS: We observed that a significant correlation between the proportion of apoptotic oligodendrocytes in the compressed area of the spinal cord and the magnitude of cord compression. Immunohistochemical analysis indicated overexpression of TNFR1, CD95, and p75NTR in the twy/twy mice, which was localized by the immunofluorescence in the neurons and oligodendrocytes. CONCLUSION: The expression of such factors seems to play at least some role in the apoptotic process, which probably contributes to axonal degeneration and demyelination in the twy/twy mice spinal cords with severe compression.

Surgical treatment of wrist joint dysfunction in rheumatoid arthritis: A report of two cases.

In rheumatoid arthritis (RA), it is important to actively treat wrist dysfunction to improve patient outcomes. Herein, we report two cases of wrist dysfunction in RA patients who required partial wrist fusion soon after drug initiation. Case 1: A 38-year-old woman was referred to our hospital because of left wrist joint pain. At the time of examination, swelling and tenderness of the left wrist joint were observed. After 6 months of medication, no improvement in symptoms was noted; therefore, partial wrist fusion was performed. Case 2: A 38-year-old woman was referred to our hospital because of right wrist joint pain. A plain X-ray image showed fusion of the carpal bones. Due to previous failure of drug treatment, the patient opted for arthrodesis. The postoperative course was good in both cases, and the pain improved. In these cases of monoarthritic RA, synovitis and bone destruction were observed, but blood tests showed no features of active disease, and drug treatment was ineffective. In such cases, early surgical treatment should be considered, rather than continuing conservative treatment, to ensure the best outcomes.

Cytokine Profile From the Ligamentum Flavum in Patients with Ossification of the Posterior Longitudinal Ligament in the Cervical Spine.

STUDY DESIGN: Histological, immunohistochemical, and suspension array analyses of cytokine expression in human cervical ossification of the posterior longitudinal ligament (OPLL). OBJECTIVES: The aim of this study was to determine whether changes in the cytokine profile reflect the maturation of chondrocytes and osteoblasts are associated with OPLL development. SUMMARY OF BACKGROUND DATA: OPLL progresses gradually over a prolonged period and may lead to serious spinal cord complications. However, treatment methods only include conservative therapy for neurological symptoms or surgical decompression, whereas preventive therapy for OPLL remains nonexistent. METHODS: Ligamentous samples were harvested from 24 patients with OPLL who underwent spinal surgery, and five control samples from cervical spondylotic myelo/radiculopathy patients without OPLL. Tissue sections were used for immunohistochemical studies and primary cells were cultured from the ligamentous samples for cytokine profiling. Using a suspension array system, concentrations of 27 inflammatory cytokines or growth factors were measured to generate the cytokine profiles. RESULTS: Suspension array and immunoblot analysis revealed significant increments in the levels of interleukin (IL)-6, IL-1α, basic fibroblast growth factor, and RANTES in patients with OPLL. Immunohistochemical analysis further revealed that these factors were present in mesenchymal cells within the degenerative portion of the ligamentous matrix. CONCLUSION: Our findings suggest that specific changes in the cytokine profile during ossification promote osteoblast differentiation, thereby providing new insights into OPLL pathogenesis. Moreover, this work supports the development of a new therapeutic method for preventing OPLL progression by regulating the cytokine profiles.Level of Evidence: 3.

Lidocaine cytotoxicity to the bovine articular chondrocytes in vitro: changes in cell viability and proteoglycan metabolism.

PURPOSE: A lot of studies on the effect of intra-articular injections are clinical, but many questions on the effect of lidocaine to articular chondrocytes remain unanswered. This study was performed to determine the effects of varying concentrations and exposure times of lidocaine on the viability and proteoglycan metabolism of chondrocytes in vitro. METHOD: Cartilage was obtained from metatarsal joints of adult bovines. Chondrocytes in alginate beads were cultured in medium containing 6% fetal calf serum at 370 mOsmol at cell densities of 4 million cells/ml. They were then cultured for 24 h under 21% oxygen with 0.125, 0.25, 0.5, and 1% lidocaine and without lidocaine as control. The cell viability profile across intact beads was determined by manual counting using fluorescent probes and transmission electron microscopy. RESULT: Lactate production was measured enzymatically as a marker of energy metabolism. Glycosaminoglycan (GAG) accumulation was measured using a modified dimethylmethylene blue assay. Cell viability decreased in a time- and dose-dependent manner in the concentration range of 0.125-1.0% lidocaine under the confocal microscope. Under the electron microscope, apoptosis increased as the concentration of lidocaine increased. GAG accumulation/tissue volume decreases as the concentration of lidocaine increased. However, GAG produced per million cells and the rate of lactate production per live cell were significantly higher for cells cultured at 0.5 and 1% lidocaine than the control group. Bovine chondrocytes cultured in alginate beads under high oxygen pressure are negatively influenced by increasing concentrations of lidocaine. CONCLUSION: Cell viability and proteoglycan production (GAG accumulation/tissue volume) decreased as the concentration of lidocaine increased. These data suggest caution in prolonged exposure of cartilage to high concentration lidocaine. Repeated joint injection of lidocaine potentially worsens osteoarthrosis by accelerating cartilage degradation.

Incidence of Cranial Adjacent Segment Disease after Posterior Lumbar Interbody Fusion Using the Cortical Bone Trajectory Technique for the Treatment of Single-Level Degenerative Lumbar Spondylolisthesis; More than a 2-Year Follow-Up.

INTRODUCTION: Posterior lumbar interbody fusion (PLIF) is a widely used effective, safe, and established treatment for degenerative spinal disorders. Adjacent segment disease (ASD) is one of the serious concerns governing the clinical results following spinal fusion surgery. Cortical bone trajectory (CBT) is an alternative and less-invasive technique for lumbar pedicle screw placement. Its unique medial and caudal entry point has the potential to prevent an iatrogenic facet joint violence leading to the ASD; however, the incidence of ASD following PLIF using the CBT technique (CBT-PLIF) remains unknown. METHODS: Among patients surgically treated with CBT-PLIF in our institute, 52 consecutive patients (13 males, 39 females) with single-level degenerative lumbar spondylolisthesis (DLS) who were followed up for at least 24 months were exclusively enrolled. Their clinical and radiological features, including the incidence of radiographical and symptomatic ASD and significantly associated factor for the developing radiographical ASD, were retrospectively measured. RESULTS: In the present study, we could confirm significant neurological improvement and reduction of the spondylolisthesis with mean follow-up period of 43 months. Radiographical and symptomatic ASD was observed in 14 (27%) and 2 (3.8%) cases, respectively. We compared these two groups and found that the latest lumbar lordosis was significantly different between the two groups, but not in age, body mass index, and Japan Orthopaedic Association score. Two patients with symptomatic ASD required additional surgical treatment around 1 year following the initial surgery. CONCLUSIONS: The present study, even though it is preliminary, revealed that CBT-PLIF can achieve a neurological improvement and an effective reduction of spondylolisthesis for the treatment of single-level DLS. The CBT technique is capable of reducing the incidence of ASD compared with the traditional technique; however, we must keep in mind that appropriate postoperative lumbar lordosis should be achieved. Larger, longer-term follow-up studies are required to elucidate the clinical output of CBT-PLIF.

Microarray analysis of expression of cell death-associated genes in rat spinal cord cells exposed to cyclic tensile stresses in vitro.

BACKGROUND: The application of mechanical insults to the spinal cord results in profound cellular and molecular changes, including the induction of neuronal cell death and altered gene expression profiles. Previous studies have described alterations in gene expression following spinal cord injury, but the specificity of this response to mechanical stimuli is difficult to investigate in vivo. Therefore, we have investigated the effect of cyclic tensile stresses on cultured spinal cord cells from E15 Sprague-Dawley rats, using the FX3000 Flexercell Strain Unit. We examined cell morphology and viability over a 72 hour time course. Microarray analysis of gene expression was performed using the Affymetrix GeneChip System, where categorization of identified genes was performed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) systems. Changes in expression of 12 genes were validated with quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The application of cyclic tensile stress reduced the viability of cultured spinal cord cells significantly in a dose- and time-dependent manner. Increasing either the strain or the strain rate independently was associated with significant decreases in spinal cord cell survival. There was no clear evidence of additive effects of strain level with strain rate. GO analysis identified 44 candidate genes which were significantly related to "apoptosis" and 17 genes related to "response to stimulus". KEGG analysis identified changes in the expression levels of 12 genes of the mitogen-activated protein kinase (MAPK) signaling pathway, which were confirmed to be upregulated by RT-PCR analysis. CONCLUSIONS: We have demonstrated that spinal cord cells undergo cell death in response to cyclic tensile stresses, which were dose- and time-dependent. In addition, we have identified the up regulation of various genes, in particular of the MAPK pathway, which may be involved in this cellular response. These data may prove useful, as the accurate knowledge of neuronal gene expression in response to cyclic tensile stress will help in the development of molecular-based therapies for spinal cord injury.

Metaphyseal-loading anterolaterally-flared femoral stem in cementless total hip arthroplasty: five- to eleven-year follow-up evaluation.

Using a nonlinear three-dimensional finite element analysis simulating loading conditions, we designed a new type of proximal-fitting, anterolaterally-flared, arc-deposit hydroxyapatite-coated anatomical femoral stem (FMS-anatomic stem; Japan Medical Materials, Osaka, Japan) for cementless total hip arthroplasty (THA) for Japanese patients with dysplastic hip osteoarthritis. The aim of the present study was to analyze the clinical and radiographic outcomes of the new stem. We reviewed 143 consecutive patients (164 hips; 13 men, 14 hips; 130 women, 150 hips; age at surgery, 56.6 +/- 7.6 years, mean +/- SD, range, 30-74) who underwent cementless THA using the FMS-anatomic stem at a single institution, with a follow-up period of 7.6 +/- 1.6 years (range, 5.3-11.0). Harris Hip score improved from 46.1 +/- 12.6 before surgery to 90.0 +/- 8.9 points post-THA. The 7.6-year survival rate of the stem was 99.0% after revision for aseptic loosening. Radiographs at follow-up confirmed the stability of the femoral stems within the femoral canal in all cases, with sufficient bone ingrowth. None of the patients had subsidence of the stem exceeding 2.0 mm within the femoral canal or changes in varus or valgus position of more than 2.0 degrees . The FMS-anatomic stem provided excellent results in patients with dysplastic hip osteoarthritis. Our analysis confirmed reduced radiolucency around the stem in Gruen zones, minimal subsidence, appropriate stress shielding, and promising medium-term stability within the femoral canal in our patients.