Publications (18) View all
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Article: Long-term Experience with Chiari’s Osteotomy
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ABSTRACT: Fifty-six years after the introduction of Chiari’s pelvic osteotomy, we report the long-term function scores and radiographic grade of osteoarthritis in 66 patients with 80 pelvic osteotomies with a minimum followup time of 27years (average, 32years; range, 27–48years). These 66 patients were those who could be contacted and who returned for a followup visit from among 450 patients operated between 1961 and 1981. Thirty-two hips (40%) in 28 patients had undergone a total joint arthroplasty after an average 26years (range, 13–41years). Forty-eight hips in 41 patients (60%) were not replaced, their Harris hip score being a median of 82 points (range, 37–100 points). For the 22 patients for whom we had complete radiographs the average preoperative CE angle was 11.6°, 48.6° (range, 31°–82.8°) immediately postoperatively, and 41.6° (range, 13.7°–90°) at last followup . Despite a functional hip score in most patients retaining their native hip, the degree of osteoarthritis progressed at last followup. We observed a similar mean age at the time of osteotomy in patients converted to total hip arthroplasty and those retaining their native hip. Age at time of surgery was inversely correlated (r = −0.78) with the interval between the osteotomy and THA. In this select patient group we found good functional outcome in patients who underwent Chiari pelvic osteotomy, with a conversion rate of 40% to total hip arthroplasty a mean of 32years after the procedure. Level of Evidence: Level IV, case series. See Guidelines for Authors for a complete description of levels of evidence.Clinical Orthopaedics and Related Research 04/2012; 467(9):2215-2220. · 2.53 Impact Factor -
Article: Polyethylene terephthalate (PET) enhances chondrogenic differentiation of ovine meniscocytes in a hyaluronic acid/polycaprolactone scaffold in vitro.
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ABSTRACT: The purpose of this study was to assess the effect of polyethylene terephthalate (PET) on proliferation, differentiation, and attachment of ovine meniscocytes seeded in a hyaluronic acid/polycaprolactone biomaterial (BF-1) BF-1 (30 % hyaluronic acid and 70 % polycaprolactone) cylinders with PET (CO-PET) or without PET, were seeded with 2 x 10(6) ovine meniscus cells. The specimens were harvested in triplets at 12 hours, seven, 14, 21 and 28 days. DNA content was measured to test proliferation, histological analysis for cell morphology, and biochemical assessment of glycosaminoglycan content and RT-PCR for type I and II collagen were used to assess differentiation, with immunohistochemistry as post-translational control. Attachment was evaluated by electronic microscopy at 28 days. DNA content was consistent and equal across groups, suggesting no effect of PET on cell proliferation. However, the BF-1 CO-PET showed a higher percentage of cells with spherical morphology which is typical for a chondrocytic phenotype. This biomaterial with PET also showed a higher type II collagen mRNA expression and an eightfold higher GAG-content than the material without PET. Small amounts of type I collagen mRNA expression were present on both materials at all time points. PCR results were confirmed by immunohistochemistry. Addition of PET to a hyaluronic acid/polycaprolactone biomaterial enhances a cartilaginous phenotype, increased type II collagen mRNA expression and a higher GAG production in ovine mensicocytes.International Orthopaedics 04/2012; 36(9):1953-60. · 2.03 Impact Factor -
Article: Anti-inflammatory activity of an ethanolic Caesalpinia sappan extract in human chondrocytes and macrophages.
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ABSTRACT: Caesalpinia sappan is a common remedy in Traditional Chinese Medicine and possesses diverse biological activities including anti-inflammatory properties. Osteoarthritis (OA) is a degenerative joint disease with an inflammatory component that drives the degradation of cartilage extracellular matrix. In order to provide a scientific basis for the applicability of Caesalpinia sappan in arthritic diseases, the present study aimed to assess the effects of an ethanolic Caesalpinia sappan extract (CSE) on human chondrocytes and macrophages. Primary human chondrocytes were isolated from cartilage specimens of OA patients. Primary cells, SW1353 chondrocytes and THP-1 macrophages were serum-starved and pretreated with different concentrations of CSE prior to stimulation with 10 ng/ml of interleukin-1beta (IL-1β) or lipopolysaccharide (LPS). Following viability tests, nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) were evaluated by Griess assay and ELISA, respectively. Using validated real-time PCR assays, mRNA levels of IL-1β, TNF-α, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were quantified. SW1353 cells were cotransfected with a COX-2 luciferase reporter plasmid and nuclear factor-kappa-B (NF-κB) p50 and p65 expression vectors in the presence or absence of CSE. CSE dose-dependently inhibited the expression of pro-inflammatory cytokines IL-1β and TNF-α in IL-1β-stimulated chondrocytes and LPS-stimulated THP-1 macrophages. CSE further suppressed the synthesis of NO in primary OA chondrocytes by blocking iNOS mRNA expression. The inhibition of COX-2 transcription was found to be related with the CSE inhibition of the p65/p50-driven transactivation of the COX-2 promoter. The present report is first to demonstrate the anti-inflammatory activity of CSE in an in vitro cell model of joint inflammation. CSE can effectively abrogate the IL-1β-induced over-expression of inflammatory mediators at the transcriptional level in human chondrocytes and macrophages, most likely by inhibiting NF-κB (p65/p50) signaling. Blockade of IL-1β-induced NF-κB signaling and its downstream pro-inflammatory targets by CSE may be beneficial for reducing cartilage breakdown in arthritis.Journal of ethnopharmacology 09/2011; 138(2):364-72. · 2.32 Impact Factor -
Article: Caesalpinia sappan extract inhibits IL1β-mediated overexpression of matrix metalloproteinases in human chondrocytes.
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ABSTRACT: Exacerbated production of matrix metalloproteinases (MMPs) is a key event in the progression of osteoarthritis (OA) and represents a promising target for the management of OA with nutraceuticals. In this study, we sought to determine the MMP-inhibitory activity of an ethanolic Caesalpinia sappan extract (CSE) in human OA chondrocytes. Thus, human articular chondrocytes isolated from OA cartilage and SW1353 chondrocytes were stimulated with Interleukin-1beta (IL1β), without or with pretreatment with CSE. Following viability assays, the production of MMP-2 and MMP-13 was assessed using ELISA, whereas mRNA levels of MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-13 and TIMP-1, TIMP-2, TIMP-3 were quantified using RT-qPCR assays. Chondrocytes were co-transfected with a MMP-13 luciferase reporter construct and NF-kB p50 and p65 expression vectors in the presence or absence of CSE. In addition, the direct effect of CSE on the proteolytic activities of MMP-2 was evaluated using gelatin zymography. We found that CSE significantly suppressed IL1β-mediated upregulation of MMP-13 mRNA and protein levels via abrogation of the NF-kB(p65/p50)-driven MMP-13 promoter activation. We further observed that the levels of IL1β-induced MMP-1, MMP-3, MMP-7, and MMP-9 mRNA, but not TIMP mRNA levels, were down-regulated in chondrocytes in response to CSE. Zymographic results suggested that CSE did not directly interfere with the proteolytic activity of MMP-2. In summary, this study provides evidence for the MMP-inhibitory potential of CSE or CSE-derived compounds in human OA chondrocytes. The data indicate that the mechanism of this inhibition might, at least in part, involve targeting of NF-kB-mediated promoter activation.Genes & Nutrition 08/2011; 7(2):307-18. · 2.51 Impact Factor -
Article: Critical-size defect induces unicompartmental osteoarthritis in a stable ovine knee.
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ABSTRACT: Animal models simulating osteoarthritis are frequently associated with irreversible changes in biomechanics. Although these models successfully induce osteoarthritis, results of experimental repair procedures are impaired by biomechanical problems. The aim of this study was to define the critical size of a chondral lesion to induce unicompartmental osteoarthritis in a stable joint. Sixteen sheep were randomly divided into four treatment groups. A cartilage defect (7- or 14-mm diameter) was created in the weight-bearing zone of the medial femoral condyle. The sheep were mobilized for 6 or 12 weeks. Osteoarthritis was determined by gross assessment, India ink staining, histology (Mankin score), and analysis of COMP in the serum. In the 6-week group, only minor osteoarthritis was registered for either defect size. After 12 weeks, the 14-mm defect induced minor osteoarthritis at the femoral condyle and caused significant degenerative changes at the tibial articular cartilage and the meniscus. The 7-mm defect created focal unicompartmental osteoarthritis at the medial femoral condyle and minor degenerative changes at the corresponding tibia. A 7-mm full-thickness chondral defect with a weight-bearing regimen of 12 weeks induced local osteoarthritis at the medial compartment in an otherwise stable joint as aimed.Journal of Orthopaedic Research 08/2011; 30(2):214-20. · 2.81 Impact Factor
