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Case: An 18-year-old man with Ullrich congenital muscular dystrophy (UCMD) noted difficulty of looking forward and discomfort swallowing and breathing because of his hyperextended neck. We treated his cervical deformity with posterior spinal correction and fusion alone. He underwent a tracheotomy because of lung function deterioration 2 years after cervical surgery. The tracheotomy was performed safely because the anterior cervical spine anatomy was normalized and soft tissues around trachea were preserved by the posterior cervical correction. Conclusion: Cervical hyperextension can be a problem in patients with UCMD. Posterior spinal correction and fusion may be a preferable solution. [ABSTRACT FROM AUTHOR]

Study Design: An experimental animal study. Purpose: To evaluate effects of anti-vascular endothelial growth factor (VEGF) on the content and distribution of the calcitonin generelated peptide (CGRP) in the dorsal ganglia in a rat model. Overview of Literature: Increased expression of VEGF in degenerative disc disease increases the levels of inflammatory cytokines and nerve ingrowth into the damaged discs. In animal models, increased levels of VEGF can persist for up to 2 weeks after an injury. Methods: Through abdominal surgery, the dorsal root ganglia (DRG) innervating L5/L6 intervertebral disc were labeled (FluoroGold neurotracer) in 24, 8-week old Sprague Dawley rats. The rats were randomly allocated to three groups of eight rats each. The anti- VEGF group underwent L5/6 intervertebral disc puncture using a 26-gauge needle, intradiscal injection of 33.3 μg of the pegaptanib sodium, a VEGF165 aptamer. The control-puncture group underwent disc puncture and intradiscal injection of 10 μL saline solution, and the sham-surgery group underwent labeling but no disc puncture. Two rats in each group were sacrificed on postoperative days 1, 7, 14, and 28 after surgery. L1-L6 DRGs were harvested, sectioned, and immunostained to detect the content and distribution of CGRP. Results: Compared with the control, the percentage of CGRP-positive cells was lower in the anti-VEGF group (p <0.05; 40.6% and 58.1% on postoperative day 1, 44.3% and 55.4% on day 7, and 42.4% and 59.3% on day 14). The percentage was higher in the control group compared with that of the sham group (p <0.05; sham group, 34.1%, 40.7%, and 33.7% on postoperative days 1, 7, and 14, respectively). Conclusions: Decreasing CGRP-positive cells using anti-VEGF therapy provides fundamental evidence for a possible therapeutic role of anti-VEGF in patients with discogenic lower back pain. [ABSTRACT FROM AUTHOR]

Several studies have implicated ß2-microglobulin (B2M) in osteoarthritis (OA) pathology. Of the main constituents of synovial tissue, synovial fibroblasts and macrophages, the latter play a pivotal role in inflammation. Although several studies have investigated the effects of B2M on synovial fibroblasts, few have examined the impact on synovial macrophages. Here, we investigated the effect of B2M on the expression profiles of inflammatory cytokines and matrix metalloproteases (MMPs) in synovial macrophages. Synovial macrophages were isolated from the osteoarthritic synovium using an anti-CD14 antibody and magnetic isolation system. Synovial macrophages were stimulated with B2M for 6 and 24 h. Following stimulation, cell surface marker (CD80, CD163, CD206), cytokine [interleukin (IL)-6, IL-8, tumor necrosis factor a (TNF-a)] and matrix metalloprotease (MMP; MMP-9 and MMP-13) genes were evaluated by real-time PCR. Additionally, cytokine concentrations in cell culture supernatant were determined using enzyme-linked immunosorbent assay (ELISA). B2M significantly increased CD80 and decreased CD163 expression. In addition, B2M stimulation increased inflammatory cytokines at both the mRNA and protein levels. While B2M likewise elevated MMP-13 levels, there was no difference in MMP-9 expression between vehicle and B2M-treated cells. B2M increased M1 macrophage marker, inflammatory cytokine, and MMP-13 expression in synovial macrophages. B2M-related activation of synovial macrophages may thus be associated with OA pathology. [ABSTRACT FROM AUTHOR]

Study Design: A retrospective cohort study. Purpose: This study aims to investigate postoperative shoulder imbalance (PSI) ≥5 years postoperatively in patients who underwent posterior spinal fusion using hooks at the upper instrumented vertebra (UIV) for Lenke type 1 adolescent idiopathic scoliosis (AIS). Overview of Literature: Studies have reported PSI due to excessive correction of the main thoracic curve. Methods: We examined 56 patients with AIS who underwent a posterior spinal fusion with hooks at the UIV from 2004 to 2010. Of these, we enrolled 14 patients who underwent surgery, at least, 5 years ago. X-rays and Scoliosis Research Society-22 (SRS-22) questionnaire were administered. To evaluate the shoulder balance, T1 vertebral tilt angle (T1 tilt), clavicle angle, and radiographic shoulder height (RSH) were measured. PSI was considered as the absolute value of the postoperative RSH being ≥20 mm. Based on radiographs obtained immediately postoperatively, we divided patients into two groups as follows: the balanced group (absolute value of RSH <20 mm) and imbalanced group (absolute value of RSH ≥20 mm). Results: The frequency of PSI was 28.6% immediately postoperatively, 0% 2 years postoperatively, and 7.1% at the last follow-up. In the balanced group, PSI did not occur even at 2 years postoperatively or at the last follow-up. In the imbalanced group, PSI was improved in all patients 2 years postoperatively and all patients, except one patient, at the last follow-up. No significant differences were noted in the frequency of distal adding-on at 2 years postoperatively or the last follow-up between the balanced group and the imbalanced group. We observed moderate negative correlations between the absolute value of T1 tilt and the SRS-22 pain and satisfaction at the last follow-up. Conclusions: Hooks at the UIV could adjust the shoulder balance to avoid long-term PSI in patients with AIS. [ABSTRACT FROM AUTHOR]

Study Design: An in vivo histologic and magnetic resonance imaging (MRI) study of lumbar intervertebral disc (IVD) degeneration was conducted. Purpose: To clarify the sensitivity and efficacy of T1ρ/T2 mapping for IVD degeneration, the correlation between T1ρ/T2 mapping and degenerative grades and histological findings in the lumbar IVD were investigated. Overview of Literature: The early signs of IVD degeneration are proteoglycan loss, dehydration, and collagen degradation. Recently, several quantitative MRI techniques have been developed; T2 mapping can be used to evaluate hydration and collagen fiber integrity within cartilaginous tissue, and T1ρ mapping can be used to evaluate hydration and proteoglycan content. Methods: Using New Zealand White rabbits, annular punctures of the IVD were made 10 times at L2/3, 5 times at L3/4, and one time at L4/5 using an 18-gauge needle (n=6) or a 21-gauge needle (n=6). At 4 and 8 weeks post-surgery, MRI was performed including T1ρ and T2 mapping. The degree of IVD degeneration was macroscopically assessed using the Thompson grading system. All specimens were cut for hematoxylin and eosin, safranin-O, and toluidine blue staining. Results: Disc degeneration became more severe as the number of punctures increased and when the larger needle was used. T1ρ and T2 values were significantly different between grade 1 and grade 3 IVDs, grade 1 and grade 4 IVDs, grade 2 and grade 3 IVDs, and grade 2 and grade 4 IVDs (p <0.05). There was a significant difference between grade 1 and grade 2 IVDs only in terms of T1ρ values (p <0.05). Conclusions: T1ρ and T2 quantitative MRI could detect these small differences. Our results suggest that T1ρ and T2 mapping are sensitive to degenerative changes of lumbar IVDs and that T1ρ mapping can be used as a clinical tool to identify early IVD degeneration. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective cohort study. Purpose: To investigate the effect of spinal correction on respiratory muscle strength in patients with Duchenne muscular dystrophy (DMD). Overview of Literature: Several studies have reported that scoliosis correction in patients with DMD does not improve pulmonary function. In these studies, pulmonary function was evaluated using the traditional spirometric values of percent vital capacity (%VC) and percent forced vital capacity (%FVC). However, traditional spirometry may not be suitable for patients with DMD because the results can be influenced by patient fatigue or level of understanding. Therefore, we evaluated respiratory function focusing on respiratory muscle strength using maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and sniff nasal inspiratory pressure (SNIP), in addition to %VC and %FVC. Methods: We retrospectively reviewed 16 patients with DMD who underwent spinal correction surgery between 2006 and 2011 at Kitasato University Hospital. All patients were males, and the mean age was 13.5 years. Respiratory muscle strength was evaluated using MIP, MEP, and SNIP. Measurements were obtained preoperatively and at 1 and 6 months postoperatively, and %VC and %FVC were obtained preoperatively and within 6 months postoperatively. Results: The mean preoperative and postoperative %VC values were 54.0% and 51.7%, whereas the mean %FVC values were 53.9% and 53.2%, respectively. The mean MIP, MEP, and SNIP values obtained preoperatively and at 1 and 6 months postoperatively were as follows: MIP, 40.5, 42.7 and 47.2 cm H2O; MEP, 26.0, 28.0, and 29.0 cm H2O; and SNIP, 33.4, 33.0, and 33.0 cm H2O; respectively. The mean MIP and MEP values significantly improved postoperatively. There were no significant differences in SNIP, %VC, or %FVC preand postoperatively. Conclusions: By focusing on respiratory muscle strength, our results suggest that scoliosis correction in patients with DMD might have a favorable effect on respiratory function. [ABSTRACT FROM AUTHOR]

Background: Recent studies have suggested that the tumor necrosis factor-α (TNF-α) pathway is a potential target for the management of osteoarthritis (OA). Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is essential in several cytokine-mediated cascades, including the TNF-α, interleukin-1 (IL-1), and TGF-β pathways. The role of TAK1 in synovial tissue in OA is not fully understood. Using synovial cells harvested from OA patients during surgery, we investigated whether TAK1 inhibition suppresses production of TNF-α-induced extracellular matrix degrading enzymes and expression of pain-related molecules.Methods: Synovial tissues were harvested from ten subjects with radiographic evidence of osteoarthritis (OA) during total knee arthroplasty. Synovial cells were cultured and stimulated with control (culture media), 10 ng/mL human recombinant TNF-α, or 10 ng/mL TNF-α and 10 μM of the TAK1 inhibitor (5Z)-7-oxozeaenol for 24 h. Real-time polymerase chain reaction (PCR) analysis was used to monitor expression of mRNA of the extracellular matrix degrading enzymes matrix metalloproteinase-3 (MMP-3) and a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 4 (ADAMTS-4); and of the pain-related molecules cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), and nerve growth factor (NGF). MMP-3 and NGF protein concentrations in cell supernatant were measured by enzyme-linked immunosorbent assay (ELISA). COX-2, mPGES-1 and ADAMTS-4 protein expression was also evaluated by western blotting.Results: TNF-α stimulated increases in ADAMTS-4 and MMP3 mRNA (2.0-fold and 1.6-fold, respectively, p < 0.05) and protein expression (21.5-fold and 2.0-fold, respectively). Treatment with the TAK1 inihibitor (5Z)-7-oxozeaenol reduced ADAMTS-4 and MMP3 mRNA (0.5-fold and 0.6-fold, respectively) and protein expression (1.4-fold and 0.5-fold, respectively) in OA synovial cells. COX-2, mPGES-1 and NGF mRNA (11.2-fold, 3.1-fold and 2.7-fold, respectively) and protein expression (3.0-fold, 2.7-fold and 2.2-fold, respectively) were increased by TNF-α. (5Z)-7-oxozeaenol treatment reduced mPGES1 and NGF mRNA (1.5-fold and 0.8-fold, respectively) and protein (1.5-fold and 0.5-fold, respectively).Conclusion: TAK1 plays an important role in the regulation of TNF-α induced extracellular matrix degrading enzymes and pain-related molecule expression. TAK1 may be a potential target for therapeutic strategies aimed at preventing osteoarthritis progression and pain. [ABSTRACT FROM AUTHOR]

Background: The infrapatellar fat pad (IPFP) has been implicated as a possible source of osteoarthritis (OA) development and knee pain due to the production of inflammatory mediators and the existence of nerve fibers within this structure. Calcitonin gene-related peptide (CGRP) is a vasodilatory neuropeptide that is localized to joint tissues and has recently been implicated in the development of knee OA and OA pain. To date, however, the expression levels of CGRP in the IPFP of human knee OA patients have not been examined. Methods: IFFP and synovial (SYN) tissues were harvested from 100 individuals with radiographic knee OA (unilateral Kellgren/Lawrence [K/L] grades 2-4) during total knee arthroplasty and subjected to immunohistochemical analysis for CGRP localization. In addition, the messenger RNA (mRNA) expression levels of CGRP and cyclooxygenase-2 (COX-2) in the collected tissues were evaluated and compared using real-time PCR analysis of total RNA extracts. CGRP and COX-2 mRNA expression were also compared among individuals with K/L grades 2-4. Results: CGRP-positive cells were detected in the capillaries within the IPFP and lining layer of SYN tissue. The expression levels of CGRP in the IPFP were positively correlated with COX-2 and were significantly higher than those in SYN tissue. CGRP expression in tissue from the KL4 group was twofold higher than that from the KL2 group. Conclusions: The IPFP of knee OA patients produces relatively high levels of CGRP, which may be regulated by COX-2 at the transcriptional level. Further studies are needed to determine if CGRP levels are directly linked to OA pathology. [ABSTRACT FROM AUTHOR]