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Christophe Nich,
Yuya Takakubo,
Jukka Pajarinen,
Mari Ainola,
Abdelhakim Salem,
Tarvo Sillat,
Allison J Rao,
Milan Raska,
Yasunobu Tamaki, Michiaki Takagi,
Yrjö T Konttinen,
Stuart B Goodman,
Jiri Gallo
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ABSTRACT: The generation of wear debris is an inevitable result of normal usage of joint replacements. Wear debris particles stimulate local and systemic biological reactions resulting in chronic inflammation, periprosthetic bone destruction, and eventually, implant loosening, and revision surgery. The latter may be indicated in up to 15% patients in the decade following the arthroplasty using conventional polyethylene. Macrophages play multiple roles in both inflammation and in maintaining tissue homeostasis. As sentinels of the innate immune system, they are central to the initiation of this inflammatory cascade, characterized by the release of proinflammatory and pro-osteoclastic factors. Similar to the response to pathogens, wear particles elicit a macrophage response, based on the unique properties of the cells belonging to this lineage, including sensing, chemotaxis, phagocytosis, and adaptive stimulation. The biological processes involved are complex, redundant, both local and systemic, and highly adaptive. Cells of the monocyte/macrophage lineage are implicated in this phenomenon, ultimately resulting in differentiation and activation of bone resorbing osteoclasts. Simultaneously, other distinct macrophage populations inhibit inflammation and protect the bone-implant interface from osteolysis. Here, the current knowledge about the physiology of monocyte/macrophage lineage cells is reviewed. In addition, the pattern and consequences of their interaction with wear debris and the recent developments in this field are presented. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Journal of Biomedical Materials Research Part A 04/2013; · 2.63 Impact Factor
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ABSTRACT: Biologic antirheumatic drugs (BIO) have been reported to be potent therapeutic agents in the prevention of inflammatory joint destruction in rheumatoid arthritis (RA). The aim of this study was to investigate the immune-inflammatory cells, including Toll-like receptor (TLR)-equipped cells, in synovial tissue samples from RA patients on BIO compared to patients, who are only on conventional disease-modifying antirheumatic drug (DMARD). We analyzed immune-inflammatory cells in RA synovitis in patients of BIO group (n = 20) or DMARD group (n = 20). The grading scores of synovitis was 1.7 and 1.8 in each BIO and DMARD group and correlated best with the CD3(+) T (r = 0.71/0.70, p < 0.05) and CD20(+) B (r = 0.80/0.84, p < 0.05) cells in the both groups, but less well with the CD68(+) macrophages and S-100(+) dendritic cells (DCs). Interestingly, both T (116 vs. 242, p < 0.05) and B (80 vs. 142, p < 0.05) cell counts were lower in the BIO than in the DMARD group, whereas macrophage and DC counts did not differ. In contrast, the C-reactive protein (CRP) and disease activity score DAS28-CRP did not show clear-cut correlations with the inflammatory grade of the synovitis (r range, 0-0.35). Similar numbers of cells immunoreactive for TLR-1 to TLR-6 and TLR-9 were found in synovitis in both groups. Patients clinically responding to biologics might still have the potential of moderate/severe local joint inflammation, composed in particular of and possibly driven by the autoinflammatory TLR(+) cells.
Clinical Rheumatology 02/2013; · 2.00 Impact Factor
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ABSTRACT: Minocycline-induced pigmentation of bone (black bone) is well described in tooth-bearing intra-oral bone, but is less known in periarticular bone in patients who have undergone total joint arthroplasty. On a retrospective basis, we investigated the short-term clinico-radiological results of total joint arthroplasties in which the patient developed minocycline-induced periarticular black bone.
We found 5 cases (0.08%), in 4 patients, of periarticular bone pigmentation revealed during total joint arthroplasties (2 hips, 2 knees, and 1 ankle) in our series of total joint surgeries (6,548 cases) over a 10-year time period in our 3 institutes. Their mean age was 56 years at surgery. All patients had received long-term minocycline treatment. Mean dosage and duration of minocycline was 160 mg/day and 2.2 years, respectively. Minocycline had been prescribed for reactive arthritis (one), rheumatoid arthritis (two) and late infection after total joint arthroplasty (two patients). Mean follow-up period was 3.4 years after the surgeries.
All cases had black or brown pigmentation in the periarticular bones during the surgery. There was no pigmentation in the cartilage or soft tissues of the joints. The mean Japanese Orthopaedic Association (JOA) score or Japanese Society for Surgery of the Foot (JSSF) scale for rheumatoid arthritis foot and ankle joints at latest follow-up (case 1, 66; case 2, 87; case 3, 77; case 4, 77; case 5, 80) improved compared to those of pre-surgery (case 1, 47; case 2, 45; case 3, 55; case 4, 34; case 5, 55). No implant loosening was noted on radiographic examination during the follow-up period. No abnormal bone formation, bone necrosis, hemosiderin deposition, malignancy or metallic debris was found on histological examination.
No clinico-radiological symptoms of total joint arthroplasties showed in the patients with minocycline-induced periariticular black bone in the short-term. Systemic minocycline treatment has the potential to induce significant black pigmentation of many tissues. In particular, minocycline-induced pigmentation of periarticular bone may be accelerated by inflammation due to rheumatic or pyogenic arthritis. Surgeons should recognize the risk of bone pigmentation in inflamed joints due to the systemic treatment of minocycline and explore its influence on periarticular bone and total joint arthroplasty in the long-term.
Clinics in orthopedic surgery 09/2012; 4(3):181-7.
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ABSTRACT: It was hypothesized that vascular endothelial growth factor (VEGF) in fibroblasts participates in aseptic loosening of total hip replacement (THR) implants. Therefore, osteoarthritic (OA) samples (n = 11) were compared with synovial membrane-like interface tissues from revision THR (n = 10). VEGF-A and its receptors were stained using streptavidin-immunoperoxidase method. Their regulation by hypoxia and cytokines were studied in cultured fibroblasts using quantitative real-time polymerase chain reaction (qRT-PCR). VEGFR1(+) lining cells (p < 0.01), stromal fibroblast-like cells (p = 0.001) and stromal macrophage-like cells (p < 0.05) were more numerous in rTHR than in OA. As to VEGFR2(+) , only stromal fibroblast-like cells in rTHR outnumbered those found in OA (p < 0.05). VEGFRs in synovial fibroblasts were not affected by hypoxia, but VEGF increased 2.4-fold (p < 0.05). Interleukin-4 up-regulated VEGFR1 expression 23-fold. This is the first study to describe a difference between rTHR and OA in VEGF receptors, particularly VEGFR1. Hypoxia increased VEGF, but the VEGFR1 increase in the lining and stroma is probably IL-4 driven, in accordance with the M2-type macrophage dominance in interface tissues. VEGF/VEGFR system is also affected by hypoxia and may play a role in angiogenesis and bone pathology in aseptic loosening of total hip implants. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1830-1836, 2012.
Journal of Orthopaedic Research 04/2012; 30(11):1830-6. · 2.81 Impact Factor
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Jiri Gallo,
Yrj� T. Konttinen,
Stuart B. Goodman,
Jacob P. Thyssen,
Emmanuel Gibon,
Jukka Pajarinen,
Yuya Takakubo,
Peter Schalock,
Zygmunt Mackiewicz,
Eemeli J�msen,
Martin Petrek,
Rihard Trebse,
Andrei Coer, Michiaki Takagi
01/2012; , ISBN: 978-953-307-990-5
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ABSTRACT: Osteogenic responses of human mesenchymal stromal cells (hMSCs) were compared on square-patterned, inverse square-patterned, and planar titanium, chromium, diamond-like carbon (DLC), and tantalum; hypothesis was that both the materials and patterns affect osteogenesis. Samples were produced using photolithography and physical vapor deposition. Early-marker alkaline phosphatase (ALP) and mid-markers, small body size and mothers against decapentaplegic-related protein-1 (SMAD1), runt-related transcription factor-2 (RUNX2), and osteopontin were studied using quantitative real-time polymerase chain reaction. ALP and hydroxyapatite, were colorimetrically studied. ALP reached highest values on both patterned titanium samples, but mid-markers disclosed that it was already lagging behind planar and inverse patterned tantalum. Hydroxyapatite formation disclosed that osteo-induced hMSCs passed all the differentiation stages (except on planar chromium). Presence of hydroxyapatite disclosed that both types of patterning promoted (p < 0.001) osteogenesis compared to planar samples. Results suggest that the osseocompatibility/integration of implants could be improved by changing the monotonous and featureless implant-host interface into micro-patterned interface to provide physical differentiation cues.
Journal of Biomaterials Applications 11/2011; · 2.08 Impact Factor
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ABSTRACT: Tacrolimus (TAC) suppresses immune-inflammation by an intermediary inhibition of calcineurin activation in the treatment of rheumatoid arthritis (RA). Various combination therapies for RA have been reported to be superior to monotherapies. The aim was therefore to study add-on TAC in a combination with biologics (BIO) and/or non-BIO disease-modifying anti-rheumatic drugs (DMARDs) in treatment-resistant patients. In eight RA patients, TAC was added on to BIO (TAC/BIO group) and in forty-one to non-BIO DMARDs (TAC/non-BIO group). The mean C-reactive protein (CRP) decreased from 33 mg/l at the baseline to 16 mg/l at first year in the TAC/BIO group (P < 0.05), from 41 to 14 mg/l in the TAC/non-BIO group (P < 0.05); the mean DAS28-CRP (28 joint count) disease activity score decreased from 5.3 to 4.4 in the TAC/BIO group (P < 0.05) and from 5.0 to 3.9 in the TAC/non-BIO group (P < 0.05). The median of Δ modified total Sharp score decreased from 43 during the year preceding the baseline to 3 during the first year of the follow-up in the TAC/BIO group (P < 0.05) and from 22 to 0 during the second year in the TAC/non-BIO group (P < 0.05). Twenty-six adverse events occurred in this study in 26 patients (53% in all); however, the only severe adverse event was one case of an atypical mycobacterial disease (2%). The combination therapy of TAC with BIO or non-BIO DMARDs represents an effective and relatively safe mode of therapy in treatment-resistant RA.
Rheumatology International 11/2011; · 1.88 Impact Factor
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ABSTRACT: During adipogenic differentiation human mesenchymal stem cells (hMSC) produce collagen type IV. In immunofluorescence staining differentiating hMSCs started to express collagen type IV when Oil Red O-positive fat droplets appeared intracellularly. Quantitative real time-polymerase chain reaction confirmed progressive increase of collagen type IV α1 and α2 mRNA levels over time, 18.6- and 12.2-fold by day 28, respectively, whereas the copy numbers of α3-α6 mRNAs remained rather stable and low. Type IV collagen was in confocal laser scanning microscopy seen around adipocytes, where also laminins and nidogen were found, suggesting pericellular deposition of all key components of the fully developed basement membrane. Immunofluorescence staining of matrix metalloproteinase-2 (MMP-2, 72 kD type IV collagenase, gelatinase A) and MMP-9 (92 kD type IV collagenase, gelatinase B) disclosed only faint staining of MSCs, but MMP-9 was strongly induced during adipogenesis, whereas MSC supernatants disclosed in zymography pro-MMP-2 and faint pro-MMP-9 bands, which increased over time, with partial conversion of pro-MMP-2 to its active 62 kD form. Differentiation was associated with increasing membrane type 1-MMP/MMP-14 and tissue inhibitor of metalloproteinase-2 (TIMP-2) staining, which may enable participation of type IV collagenases in basement membrane remodelling via ternary MT1-MMP/TIMP-2/MMP-2 or -9 complexes, focalizing the fully active enzyme to the cell surface. MMP-9, which increased more in immunofluorescence staining, was perhaps preferentially bound to cell surface and/or remodelling adipocyte basement membrane. These results suggest that upon MSC-adipocyte differentiation collagen type IV synthesis and remodelling become necessary when intracellular accumulation of fat necessitates a dynamically supporting and instructive, partly denatured adipogenic pericellular type IV collagen scaffold.
Journal of Cellular and Molecular Medicine 08/2011; 16(7):1485-95. · 4.13 Impact Factor
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ABSTRACT: The aim of this study was to estimate the effective administration procedure of fondaparinux for prevention of venous thromboembolism after cemented total hip replacement (THR) in Japanese patients. The study included 471 Japanese patients. The dose regimens were 2.5 mg daily for 14 days (2.5 mg/14 day group) or 10 days (2.5 mg/10 day group), 1.5 mg daily for 10 days (1.5 mg group), 2.5 mg daily for the first 3 postoperative days and 1.5 mg daily for the subsequent 7 days (Mixed group), and no administration of fondaparinux (Control group). Deep venous thrombosis (DVT) was diagnosed by ultrasonography on postoperative day 3 or 4 and day 14. The 2.5 mg/14 day, 2.5 mg/10 day and Mixed groups were regarded as one group in the assessment on postoperative day 3 or 4, and denoted as the 2.5 mg group. The incidence of DVT on postoperative day 3 or 4 in the 2.5 mg group was significantly lower than that in the Control and 1.5 mg groups. On postoperative day 14, the incidence of DVT in the 1.5 mg and Mixed groups was significantly lower than that in the Control group in both the intention-to-treat and per-protocol analyses. The incidence in the 2.5 mg/10 day and 2.5 mg/14 day groups was significantly lower than that in the Control group in only the per-protocol analysis. The results suggest that the administration protocol of the Mixed group is effective in preventing DVT in Japanese patients undergoing cemented THR.
Modern Rheumatology 07/2011; 22(2):216-22. · 1.58 Impact Factor
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ABSTRACT: Macrophages phagocytose metallic wear particles and produce mediators, which can induce cellular host response and aseptic implant loosening. Lipopolysaccharide (LPS) on the wear debris can stimulate macrophages via Toll-like receptor 4 (TLR4) and enhance the response. However, the precise functional role and interaction of TLRs and their adaptor molecules is still unclear. Rat bone marrow macrophages were stimulated with titanium particle (Ti) coated by LPS (Ti/LPS+) and LPS-free Ti (Ti/LPS-). mRNA levels of cytokines, TLRs and their adaptor molecules were measured using real time PCR. mRNA levels of TNF-α, IL-1β, and IL-6 increased in Ti/LPS+ than Ti/LPS-. In contrast, mRNA levels of TLR4, TLR5, and TLR9 decreased in Ti/LPS+ compared to Ti/LPS-. mRNA levels of MyD88, IRAK1, IRAK4 decreased gradually, and TRAF6 underwent an initial transient increase, followed by suppression in Ti/LPS+. However, mRNA levels of TLR2 and IRAK2 increased after phagocytosis of Ti/LPS+ than Ti/LPS-. The increased expressions of proinflammatory cytokines found in Ti/LPS+ indicated that their productions cytokines could be enhanced by phagocytosis of LPS-coated particles. Subsequent down-regulation of TLR4, TLR5, TLR9, MyD88, IRAK1, and IRAK4 suggests that self-protective mechanisms to regulate excessive host responses are activated in macrophages. Increase of TLR2 and IRAK2 and a transient increase of TRAF6 in Ti/LPS+ suggest that another possible pathway to modulate TLR-mediated cellular response to prolong inflammatory response in foreign body reaction of aseptic loosening. This down- and/or up-regulation of the potential TLR-mediated responses to LPS-coated particles reflects the proactive behavior of effector cells.
Journal of Orthopaedic Research 02/2011; 29(7):984-92. · 2.81 Impact Factor
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ABSTRACT: Toll-like receptors (TLR) recognizing endogenous and exogenous danger signals could play a role in rheumatoid arthritis (RA). Our aim was to describe the presence, localization, and extent of expression of TLR and their adapters.
TLR 1, 2, 3, 4, 5, 6, and 9 receptors, and myeloid differentiation primary response protein 88, Toll/interleukin receptor (TIR) domain-containing adapter protein MyD88 adapter-like, and TIR domain-containing adapter-inducing interferon/TIR-containing adapter molecule-1 adapters were analyzed in RA (n = 10) and osteoarthritis (OA; n = 5) samples using real-time polymerase chain reaction (PCR). Their colocalization with cellular markers CD68, CD15, CD3, CD4, CD8, CD20, dendritic cell lysosomal-associated membrane protein (DC-LAMP), CD123, and 5B5 was analyzed in double immunofluorescence staining.
In RA, ß-actin standardized messenger RNA of TLR 2, 3, and 9 (p < 0.001) were particularly high. TLR 5 and 6 were also elevated (p < 0.05), but TLR 1 and 4 and adapters did not differ between RA and OA. In double-staining, TLR and adapters were strongly labeled in myeloid and plasmacytoid dendritic cells (DC), moderately in CD68+ type A lining cells/macrophages, and weakly to moderately in 5B5+ type B lining cells/fibroblasts. CD3+/CD4+ and CD3+/CD8+ T cells and CD20+ B cells in perivenular areas and in lymphoid follicles were moderately TLR- and weakly adapter-positive. In OA, TLR and adapters were weakly immunolabeled in vascular, lining, and inflammatory cells.
RA synovium showed abundant expression of TLR. RA synovitis tissue seems to be responsive to TLR ligands. DC, type A cells/macrophages, and type B cells/fibroblasts are, in that order from highest to lowest, equipped with TLR, suggesting a hierarchical responsiveness. In RA, danger-associated molecular patterns to TLR interactions may particularly drive DC to autoinflammatory and autoimmune cascades/synovitis.
The Journal of Rheumatology 02/2011; 38(5):810-20. · 3.69 Impact Factor
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ABSTRACT: Five different laminin (LM) alpha, four LM-beta, and three LM-gamma chains form the 15-16 currently known approximately 400-900 kDa heterodimeric LM-monomers, which self-assemble in the lamina lucida of the basement membrane (BM) to a network, connected with nidogens and perlecans with the underlying type IV collagen network. In labial salivary glands (LSG), the structurally organizing/polarizing BM separates the tubuloacinar epithelium from the connective tissue stroma but plays regulatory roles as well. Tissue distribution of LM-alpha, -beta, and -gamma chains is described, and application of the known combinatorial rules allows some conclusions also on the corresponding distribution of the LM-trimers. Currently, known integrin (Int) and non integrin (e.g., dystroglycans and Lutheran blood group antigens) LM-receptors are described. LMs are regulated at transcriptional, translational, and posttranslational levels, together with the regulation of alternative splicing, binding partners (assembly), secretion, and degradation. In LSGs, LM-alpha1, -alpha2, and -alpha4 are only found in the acinar (not ductal) BM, LM-alpha4 also in the periductal/ interstitial stroma. Pattern recognition disclosed irregular expression in the acinar BM, suggesting some dynamic and/or regulatory role. It seems that in a female-dominant autoimmune exocrinopathy, Sjögren's syndrome (SS), LM-alpha1 and -alpha2 are decreased, together with their Int alpha1beta1 and alpha2beta1 receptors. Because LM-111/211-to-Int-alpha1beta1/alpha2beta1 interactions play a crucial role in the transdifferentiation of the intercalated duct progenitors to secretory acinar cells, acinar remodeling is impaired in SS. Disturbed hemidesmosomal Int alpha6beta4/LM-332 interactions in SS may lead to acinar cell anoikis. Interestingly, dehydroepiandrosterone (DHEA) prohormone and its intracrine androgenic dihydrotestosterone (DHT) end product upregulate at least Int alpha1beta1/alpha2beta1, whereas LM-alpha1 is upregulated by outside-in LM-111/211-to-Int-alpha1beta1/alpha2beta1 signaling. It seems that LM alterations precede the lymphocyte infiltration, suggesting that acinar BM-Int pathology, perhaps related to endo- and intracrine sex steroid metabolism, represents an early pathogenic phases in SS.
Advances in clinical chemistry 01/2011; 55:35-59. · 3.20 Impact Factor
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Michiaki Takagi
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ABSTRACT: Toll like receptor (TLR), one of the key functions of innate immune system, can recognize not only exogenous pathogen-associated molecular patterns, namely PAMPs, but also endogenous molecules created upon tissue injury, sterile inflammation and degeneration. Endogenous TLR ligands are called as damage-associated molecular patters (DAMPs), including endogenous molecules released by activated and necrotic cells, and extracellular matrix molecules. DAMPs are also known as alarmins. TLR research has brought about new insights in the rheumatic diseases. Previous reports suggest that TLRs and the signal pathways intensively contribute to the pathogenesis of rheumatoid arthritis (RA) and other arthritic conditions with interaction of various TLR ligands. Accumulated knowledge of TLR system is summarized to overlook TLRs and the signaling pathway in arthritis conditions, with special reference to RA.
Journal of Clinical and Experimental Hematopathology 01/2011; 51(2):77-92.
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ABSTRACT: Distinction between the two major complications of total hip replacement surgery, septic bacterial culture-positive and aseptic bacterial culture-negative osteolysis and loosening, is difficult due to the eventual role of bacterial remnants and biofilms, which are recognized by cells provided by toll-like receptors (TLRs) of the innate immune system. It was hypothesized that cell typing and TLR mapping might provide new information on the pathomechanisms of loosening. To test this hypothesis, septic (n = 10) and aseptic (n = 5) interface tissue as well as mildly inflamed osteoarthritic synovial membrane (n = 5) samples were characterized and compared using antibodies against several cell line-specific markers, including fibroblast, monocyte/macrophage, T cell, B cell, plasma cell and neutrophil markers, and TLRs. In osteoarthritic synovium, TLR-positive cells were restricted to surface tissues and only few inflammatory cells were detected, whereas aseptic interface was heavily infiltrated with monocyte/macrophages, which were also the major TLR-positive cell type rendering the tissue reactive to TLR ligands. Interestingly, septic cases contained also neutrophil and lymphocyte infiltrates of which especially B-cell infiltrates might be clinically useful in discriminating the two major complications of the joint replacement surgery. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.
Journal of Biomedical Materials Research Part A 07/2010; 94(1):84-92. · 2.63 Impact Factor
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ABSTRACT: The geometry of the proximal femur is one of the important factors for choosing the suitable stem. We have been applied cemented collarless polished tapered (CPT) stem to the patients with small femur. Radiographic evaluation was performed to access the clinical feature of the stem in early stage of the follow-up.
One hundred total hip arthroplasties with CPT system were performed between October 2004 to February 2006. This study focused on the 53 cases to whom size 1 or smaller sized stem were implanted, and its post-operative period was 41 months (30-46 months). Morphologic classification of preoperative proximal femur, stem alignment, thickness of the cement mantle, cementing technique, subsidence of the stem, improvement in the bone-cement interface, and stress shielding were assessed.
The size of the inserted stem was X-SMALL in one case, SMALL in two cases, SIZE 0 in 12 cases, and SIZE 1 in 38 cases. Canal shape of proximal femur was stovepipe type in five cases, normal type in 43 cases, and champagne-flute type in five cases. There was no subsidence in eight cases. 44 stems subsided within 1 mm, one stem subsided 1 to 2 mm, and no stem subsided over 2 mm. In 39 of 45 cases, subsidence was appeared within six months after operation. Marked progressive and excessive subsidence was not seen after the two years of follow-up.
Short term radiographic results of THA with CPT stem to small femur were satisfactory with less unfavorable radiographic findings, which imply contribution to longer survivorship of the stem.
The Open Orthopaedics Journal 01/2010; 4:147-51.
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ABSTRACT: This study aimed to evaluate joint-preserving procedures by a modified Mann method for rheumatoid forefoot deformities and their functional outcomes in the mid-term. Eleven feet in seven patients underwent forefoot surgery using a modified Mann method for the big toe, combined with offset osteotomy or resection arthroplasty of the lesser toes. The mean follow-up period was 3.6 years. The mean score on the Japanese Society for Surgery of the Foot scale for rheumatoid arthritis foot and ankle joints improved from 44.0 to 72.0. The mean hallux valgus angle improved from 39.4 degrees to 20.5 degrees and the mean M1M5 angle improved from 31.1 degrees to 25.8 degrees . However, deformities involving a hallux valgus angle of more than 25.0 degrees recurred in three feet at the latest follow-up, although the patients did not complain of any symptoms from the recurrence. Improvement in the Sharp score for joint space narrowing was observed in the big toe, indicating better congruity of the metatarsophalangeal joint. For restraint of rheumatoid forefoot deformities, a modified Mann method, combined with offset osteotomy or resection arthroplasty, was satisfactory for not only improving the foot function, but also preserving the metatarsophalangeal joint mobility.
Modern Rheumatology 12/2009; 20(2):147-53. · 1.58 Impact Factor
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ABSTRACT: Periprosthetic infection is one of the serious complications after total hip arthroplasty (THA). This study analyzed the perioperative and postoperative status of patients who underwent antibiotics-impregnated cement spacer technique in the first step of the two-stage revision.
Ten joints of the nine patients (mean age, 65 years; seven women, two men) received two-stage revision as a result of infection that appeared after primary THAs in seven joints, aseptic revision in one, and recurrent type in two. An antibiotics-impregnated cement spacer made by a mold system was applied in the femoral side of all joints. An acetabular spacer was made by hand using a cup gauge in eight joints with extensive tissue loss.
The change of leg length after the first stage was -2.2 mm, and range of hip flexion was 72 degrees on average, respectively. Patients could walk with crutches after the first stage, except one patient with simultaneous infections of both hips and one with fracture of the cement spacer. One fracture of femoral cement spacer, and one dislocation of femoral spacer accompanied by fracture of acetabular cement spacer and curable recurrent infection, were found. In all cases of the second-stage procedure, the acetabular side was reconstructed with allogeneic bone graft with cross plate and that of the femur was by impaction bone grafting method. In the latest follow-up, reconstructed implants were stable. Seven patients could walk without any supportive devices and two could walk with the support of a T-cane.
An antibiotics-impregnated cement spacer in the first step of the two-stage revision was effective not only to compensate tissue loss after removal of the implants and to minimize discrepancy of leg length, but also to contribute to improvement of perioperative and postoperative daily activities of the patient's life as well as treatment of the infection.
Journal of Orthopaedic Science 11/2009; 14(6):704-10. · 0.84 Impact Factor
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ABSTRACT: The flexible endoscope was applied to cemented femoral medullary canal to obtain better visual field and assist surgical procedures in total hip revision arthroplasty.
Fifteen cases of failed cemented total hip joints were analyzed. Efficacy of cement removal was assessed, combined with degree of implant loosening and bone defect, postoperative radiographic findings, and perioperative status of the patients and complications. Status of the bone bed between bone and cement and that of bone grafting were also evaluated.
The cement mantle was efficiently extractable in all cases under good exposure and with maintenance of efficient working space. Endoscopic time for cement removal was dependent on the status of the cement-bone interface and bone defect. Rigid and less loosened interfaces, as well as cases of minimal bone defect, required a longer time. However, it was effective to confirm the status of the bone bed during the procedure. Occult foreign-body reaction was detectable in three cases of unloosened interface under endoscopic inspection. Impaction bone grafting was performed in eight cases. The scope was also helpful to confirm the status of a grafted bone bed. Three fractures occurred, of which two cases revealed minor cement leakage and one required additional osteosynthesis with extensive approach. JOA Hip Score was improved, and the implants were stable at latest follow-up. Dislocation was found in two cases. Neither thromboembolic events nor infection was found.
Cement removal in the femoral medullar canal was effectively performed not only in the cases of loose interface but also those of rigid and less-loosened interface under flexible endoscopic inspection. The scope could support cement removal in femoral revisions under good exposure and maintenance of working space, as well as confirmation of bone bed state. Although one case required an additional approach, application of the flexible endoscope has potential merit to contribute to less invasive total hip revision arthroplasty, possibly combined with other refined devices of cement extraction.
Journal of Orthopaedic Science 11/2009; 14(6):719-26. · 0.84 Impact Factor
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ABSTRACT: There are no data about the expression pattern of activating transcription factor 5 (Atf5) during limb development. The aim of the present study was to describe the expression of Atf5 throughout mouse limb development. Some specimens were examined for the expression of type II collagen alpha1 (Col2a1), sex-determining region Y-related high-mobility-group-box 9 (Sox9), and activating transcription factor 2 (Atf2) by in situ hybridization. ATDC5 cells, mouse limb buds, and epiphyseal cartilage were examined for the expression of Atf5alpha and Atf5beta by quantitative real-time PCR. Atf5 transcripts were detected in condensed mesenchymal cells, cartilage primordia, proliferative, prehypertrophic, and articular chondrocytes, but not in hypertrophic chondrocytes. Atf5 was predominantly expressed by osteoblasts in the primary spongiosa. At the postnatal stage, Atf5 was expressed in epiphyseal chondrocytes and osteoblasts lining the bone trabeculae. Spatial distribution of Col2a1, Sox9, and Atf2 transcripts closely corresponded to that of Atf5 within developing limbs, except for bony tissues. In cartilage, Atf5alpha is the dominant form in the embryonic stage as well as in the postnatal stage.
Embryologia 10/2009; 51(7):669-76. · 2.21 Impact Factor
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ABSTRACT: The role of Toll-like receptors (TLRs) responding to microbial remnants, indolent biofilms or cellular byproducts in aseptic loosening of joint replacements is unknown. Thus, the effect of titanium (Ti) particles on TLR protein levels was evaluated. To create a model of particle-induced inflammation, an intramedullary stainless steel rod with and without Ti particles was bilaterally placed in the femora of 14 mice. The animals were sacrificed at 2 or 10 weeks postoperatively and paraffin-embedded femur sections were evaluated for TLR1, 2, 4, 5, 8, and 9 proteins using immunohistochemistry. Decrease in the number of TLR immunoreactive cells was observed between weeks 2 and 10 in both settings. Furthermore, in the presence of Ti particles, the numbers of TLR immunoreactive cells were lower than in the presence of rod only at both time points, suggesting downregulation of TLR expression by Ti-particles per se. Accordingly, in a short-term 24 h stimulation, downregulation of TLR4 mRNA (p < 0.02) was observed in vitro in RAW 264.7 cells challenged with Ti particles. Results suggest that after an initial inflammatory stage, TLRs are downregulated in response to Ti particles, possibly to inhibit excessive inflammation, although TLR downregulation might at the same time render tissues more susceptible to pathogens.
Journal of Biomedical Materials Research Part A 05/2009; 92(4):1528-37. · 2.63 Impact Factor
