Emeritus Faculty, Acad Council, Orthopaedic Surgery
Cartilage degradation and arthritis
This study examined effects of varying magnitudes of intermittent hydrostatic pressure (IHP) applied for different times on chondrogenesis of adult human mesenchymal stem cells (hMSCs) in vitro. hMSCs were exposed to 0.1, 1, and 10 MPa of IHP at a frequency of 1 Hz for 4 h/day for 3, 7, and 14 days in the presence of transforming growth factor (TGF-beta3). Chondrogenesis was characterized by gene expression, macromolecule production, and extracellular matrix deposition. Exposure of hMSCs to 0.1 MPa of IHP increased SOX9 and aggrecan mRNA expression by 2.2- and 5.6-fold, respectively, whereas type II collagen mRNA expression responded maximally at 10 MPa. Production of sulfated glycosaminoglycan responded to IHP of 1 MPa and 10 MPa, whereas collagen levels increased only at 10 MPa. Morphologically, matrix condensation occurred with increased IHP, concomitant with collagen expression. This study demonstrated that different levels of IHP differentially modulate hMSC chondrogenesis in the presence of TGF-beta3. The data suggest that tissue engineering of articular cartilage through application or recruitment of hMSCs can be facilitated by mechanical stimulation.
View details for Web of Science ID 000240345800019
View details for PubMedID 16968165
This study examined the effects of intermittent hydrostatic pressure (IHP) and transforming growth factor-beta 3 on chondrogenesis of adult human mesenchymal stem cells (hMSCs) in vitro. Chondrogenic gene expression was determined by quantifying mRNA signal levels for SOX9, a transcription factor critical for cartilage development and the cartilage matrix proteins, aggrecan and type II collagen. Extracellular matrix production was determined by weight and histology. IHP was applied to hMSCs in pellet culture at a level of 10 MPa and a frequency of 1 Hz for 4 h per day for periods of 3, 7, and 14 days. hMSCs responded to addition of TGF-beta 3 (10 ng/mL) with a greater than 10-fold increase (p < 0.01) in mRNA levels for each, SOX9, type II collagen, and aggrecan during a 14-day culture period. Applying IHP in the presence of TGF-beta 3 further increased the mRNA levels for these proteins by 1.9-, 3.3-, and 1.6-fold, respectively, by day 14. Chondrogenic mRNA levels were increased with just exposure to IHP. Extracellular matrix deposition of type II collagen and aggrecan increased in the pellets as a function of treatment conditions and time of culture. This study demonstrated adjunctive effects of IHP on TGF-beta 3-induced chondrogenesis and suggests that mechanical loading can facilitate articular cartilage tissue engineering.
View details for Web of Science ID 000239570400004
View details for PubMedID 16846340
Range of motion after total knee arthroplasty is an important variable in determining clinical outcome. The goal of this study was to assess range of motion across five types of posterior-stabilized knee prostheses used sequentially in the same institution during 17 years. The hypothesis was that absolute flexion would improve in newer models of this basic prosthesis design. Only primary knee arthroplasties in patients with osteoarthritis were evaluated. A retrospective analysis was done. Three hundred fifty-eight knees with osteoarthritis were reviewed. The average arc of motion was 103 degrees before surgery and 111 degrees after surgery. Absolute flexion was clinically similar but improved from before surgery (110 degrees ) to after surgery (113 degrees ). No difference was found when comparing improvements in range of motion among the different types of prostheses used. This study did not show that any knee system made a difference in determining the final range of motion postoperatively. Height emerged as a predictive factor of absolute flexion. Preoperative range of motion is the most important variable in determining improvements in range of motion, with height playing a secondary role. Level of Evidence: Prognostic study, Level II-1.
View details for DOI 10.1097/01.blo.0000146745.13678.b9
View details for Web of Science ID 000226145500017
View details for PubMedID 15662314
The development, maintenance, and destruction of cartilage are regulated by mechanical factors throughout life. Mechanical cues in the cartilage fetal endoskeleton influence the expression of genes that guide the processes of growth, vascular invasion, and ossification. Intermittent fluid pressure maintains the cartilage phenotype whereas mild tension (or shear) promotes growth and ossification. The articular cartilage thickness is determined by the position at which the subchondral growth front stabilizes. In mature joints, cartilage is thickest and healthiest where the contact pressure and cartilage fluid pressure are greatest. The depth-dependent histomorphology reflects the local fluid pressure, tensile strain, and fluid exudation. Osteoarthritis represents the final demise and loss of cartilage in the skeletal elements. The initiation and progression of osteoarthritis can follow many pathways and can be promoted by mechanical factors including: (1) reduced loading, which activates the subchondral growth front by reducing fluid pressure; (2) blunt impact, causing microdamage and activation of the subchondral growth front by local shear stress; (3) mechanical abnormalities that increase wear at the articulating surface; and (4) other mechanically related factors. Research should be directed at integrating our mechanical understanding of osteoarthritis pathogenesis and progression within the framework of cellular and molecular events throughout ontogeny.
View details for DOI 10.1097/01.blo.0000144970.05107.7e
View details for Web of Science ID 000224524400014
View details for PubMedID 15480079
The treatment of osteoarthritis includes a wide spectrum of approaches. This article reviews current practices in medical, pharmaceutical and surgical treatment with a perspective toward the immediate, distant and far distant future. At present, with the exception of surgery, all other treatments are palliative. That is to say that many of these treatments relieve pain and increase function. However, on the basis of medical evidence, these treatments do not change the course of the disease. Surgical interventions, including joint replacement and osteotomy, reverse the progress of osteoarthritis and provide long-term improved function and pain relief for specific joints. The goal of treating osteoarthritis is to arrest and reverse its progress regionally or globally through biologic methodology. Meaningful progress for biologic intervention accumulates annually. Pluripotent mesenchymal cells can be coaxed into chondrocytes or stem cells. Cytokines, growth factors, chemokines, protease inhibitors, kinases, apoptosis, mechanics, and genetics are increasingly recognized to play key roles in the control of the articular cartilage behavior. Knowledge of their roles and relationships advance toward solutions related to osteoarthritis. In the future, biologic control may be harnessed to regrow joints or limbs, as currently occurs naturally in newts and salamanders. Fortunately, until then we have ever improving joint replacement.
View details for DOI 10.1097/01.blo.0000143555.33848.c4
View details for Web of Science ID 000224524400031
View details for PubMedID 15480065
Homeostasis of articular cartilage depends in part on mechanical loads generated during daily activity whereas inappropriate joint loads result in focal degeneration of cartilage, as occurs in osteoarthritis. We will review results of a series of questions regarding the effects of two types of mechanical loads-intermittent hydrostatic pressure and shear stress-on adult human articular chondrocytes in high-density monolayer culture. Intermittent hydrostatic pressure increased aggrecan and Type II collagen gene expression in normal chondrocytes and induced changes in the cell-associated proteins of normal and osteoarthritic chondrocytes. Hydrostatic pressure also counteracted inhibitory effects of bacterial lipopolysaccharide on matrix protein expression by cultured chondrocytes. Application of shear stress to osteoarthritic chondrocytes increased the release of the proinflammatory mediator, nitric oxide, decreased aggrecan and Type II collagen expression, and induced molecular changes associated with apoptosis whereas hydrostatic pressure increased matrix macromolecule expression. The findings show that the types of load comprising the mechanical loading environment of articular cartilage considerably alter chondrocyte metabolism and suggest that mechanical stimulation may be used for in vitro or in vivo approaches for cartilage engineering.
View details for DOI 10.1097/01.blo.0000143938.30681.9d
View details for Web of Science ID 000224524400016
View details for PubMedID 15480081
This study tested the hypothesis that intermittent hydrostatic pressure applied to human osteoarthritic chondrocytes modulates matrix metalloproteinase and pro-inflammatory mediator release in vitro.Human osteoarthritic articular chondrocytes were isolated and cultured as primary high-density monolayers. For testing, chondrocyte cultures were transferred to serum-free medium and maintained without loading or with exposure to intermittent hydrostatic pressure (IHP) at 10 MPa at a frequency of 1 Hz for periods of 6, 12 and 24 h. Levels of matrix metalloproteinase-2, -9 (MMP-2, -9), tissue inhibitor of metalloproteinase-1 (TIMP-1), and the pro-inflammatory mediators, interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1), released into the culture medium were assessed by ELISA. Matrix metalloproteinase activity was confirmed by zymographic analysis.In the absence of IHP, levels of MMP-2, TIMP-1, IL-6, and MCP-1 in the chondrocyte culture medium increased in a time-dependent manner. Application of IHP decreased MMP-2 levels at all time periods tested, relative to unloaded control cultures maintained for the same time periods. Although 84/82 kDa bands were faintly detectable by zymography, MMP-9 levels were not quantifiable in medium from loaded or unloaded cultures by ELISA. TIMP-1 levels were not altered in response to IHP at any time period tested. IL-6 and MCP-1 levels decreased in cultures exposed to IHP at 12 and 24 h, relative to unloaded control cultures maintained for the same time periods.IHP decreased release of MMP-2, IL-6 and MCP-1 by osteoarthritic chondrocytes in vitro suggesting that pressure influences cartilage stability by modulating chondrocyte expression of these degradative and pro-inflammatory proteins in vivo.
View details for DOI 10.1016/j.joca.2004.05.008
View details for Web of Science ID 000224046200007
View details for PubMedID 15325639
Primary total hip replacement performed through an incision that is =10 cm in length has been advocated as a minimally invasive technique. Proponents have claimed that mini-incision techniques reduce blood loss, transfusion requirements, postoperative pain, and the length of the hospital stay compared with standard techniques through a longer incision. However, we are aware of no well-designed comparison study that supports these claims. The purpose of the present study was to compare the short-term results of a mini-incision with a standard incision technique for total hip replacement.A consecutive series of patients who underwent 135 primary unilateral total hip replacements (fifty with use of a mini-incision [=10 cm] and eighty-five with use of a standard incision) by three surgeons at one hospital were studied. Each surgeon selected patients to have a mini-incision procedure and performed a standard approach in the remaining patients. A posterior approach was used for all procedures. In-hospital data were collected retrospectively, and the initial postoperative radiographs were analyzed. Because of the selection process, the patients who had a mini-incision had both a significantly lower average body-mass index (p = 0.008) and a lower average score on the American Society of Anesthesiologists rating (p = 0.006), indicating that they were thinner and healthier than the patients who had a standard incision.With the numbers of patients available, no significant differences were found between the groups with respect to the average surgical time, intraoperative blood loss, in-hospital transfusion rate, length of hospital stay, or the patients' disposition after discharge. The mini-incision group was found to have a significantly higher risk of a wound complication (p = 0.02), a higher percentage of acetabular component malposition (p = 0.04), and poor fit and fill of femoral components inserted without cement (p = 0.0036).There was no evidence that the mini-incision technique resulted in less bleeding or less trauma to the soft tissues of the hip, factors that would have produced a quicker recovery and a shorter hospital stay, than did the standard technique. The present study, which was based on the authors' initial experience with the mini-incision technique, failed to confirm the positive clinical outcomes reported by previous uncontrolled cohort studies, and the findings suggest that further analysis of this new technique is needed before it can be recommended for general use.
View details for PubMedID 15252080
Patients undergoing revision total hip arthroplasty frequently require perioperative blood transfusion, increasing the risk for blood-borne disease and anaphylactic and hemolytic reactions. The purpose of this retrospective study was to evaluate the effect of intraoperative blood collection and reinfusion on net blood loss in patients undergoing revision hip arthroplasty.The medical records of 126 patients who had had a revision total hip arthroplasty with intraoperative blood salvage, with use of a collection and reinfusion device, during a twenty-eight-month period were reviewed. For comparison, the medical records of ninety-six patients who had undergone revision hip arthroplasty without intraoperative blood salvage were reviewed. Each of the 222 patients was categorized into a group on the basis of the type of revision.Patients who had a revision of the femoral and acetabular components (Group C) had significantly higher mean intraoperative and total blood loss than did those who had a revision of the femoral component only (Group A [p = 0.009 and p = 0.02, respectively]) or a revision of the acetabular component only (Group B [p = 0.0001 for both]). Total blood loss was not significantly different between Groups A and B. The mean amount of blood reinfused intraoperatively was 356 mL for the patients in Group A, 374 mL for the patients in Group B, and 519 mL for the patients in Group C. Regression analysis showed a significant decrease in net blood loss with intraoperative collection and reinfusion in Groups B (p = 0.002) and C (p = 0.0001) but not in Group A.Intraoperative collection and reinfusion substantially decreased net perioperative blood loss in patients who had a revision of both components (Group C) and in those who had a revision of the acetabular component (Group B). The use of intraoperative blood collection and reinfusion appears to be a valuable method of preserving blood volume in the perioperative period.
View details for PubMedID 14630844
Onset and progression of cartilage degeneration is associated with shear stress occurring in diarthrodial joints subjected to inappropriate loading. This study tested the hypothesis that shear stress induced nitric oxide is associated with altered expression of regulatory onco-proteins, bcl-2, and Fas (APO-1/CD95) and apoptosis in primary human osteoarthritic chondrocyte cultures. Shear stress induced membrane phosphatidylserine and nucleosomal degradation were taken as evidence of chondrocyte apoptosis. Application of shear stress upregulated nitric oxide in a dose-dependent manner and was associated with increases in membrane phosphatidylserine and nucleosomal degradation. Increasing levels of shear stress decreased expression of the anti-apoptotic factor, bcl-2, from 44 to 10 U/ml. Addition of the nitric oxide antagonists, L-N(5)-(1-iminoethyl) ornithine and Nomega-nitro-L-arginine methyl ester (L-NAME), reduced shear stress induced nucleosomal degradation by 62% and 74%, respectively. Inhibition of shear stress induced nitric oxide release by L-NAME coincided with a 2.7-fold increase of bcl-2, when compared to chondrocytes exposed to shear stress in the absence of L-NAME. These data suggest that shear stress induced nitric oxide is associated with changes in apoptotic regulatory factors that alter chondrocyte metabolism and may contribute to joint degeneration.
View details for DOI 10.1002/jcb.10611
View details for Web of Science ID 000185103600009
View details for PubMedID 12938158
VEGF and VEGF receptor, Flt-1, expression was observed in periprosthetic tissues surrounding loosened total joint implants. Exposure of monocyte/macrophages to titanium particles resulted in increased VEGF expression, p44/42 MAPK activation, and VEGF-dependent macrophage chemotaxis. Increased levels of angiogenic factors, such as VEGF, may be critically important in wear debris-induced implant loosening after total joint arthroplasty.Periprosthetic osteolysis after total hip arthroplasty occurs in association with formation of a vascularized granulomatous tissue in response to particulate debris.This study examined expression of vascular endothelial growth factor (VEGF) and the VEGF receptor in 10 periprosthetic tissues from loosened prostheses and quantified effects of titanium particles on VEGF release, intracellular signaling, and VEGF-dependent chemotaxis in primary cultures of human monocyte/macrophages.Double immunofluorescent staining showed that VEGF and Flt-1 co-localized with cells positive for the macrophage marker, CD11b, in the periprosthetic tissues. Monocyte/macrophages challenged with titanium particles showed a dose- and time-dependent release of VEGF ranging from 2.8- to 3.1-fold and exhibited increased expression of VEGF121 and VEGF165 mRNAs, reaching levels up to 5.0- and 8.6-fold, respectively, by 48 h (p < 0.01). Exposure of monocyte/macrophages to titanium particles upregulated phosphorylated-p44/42 mitogen-activated protein kinase (MAPK) within 30 minutes. Particle-induced activation of p44/42 MAPK and release of VEGF were dose-dependently suppressed by pretreatment of cells with PD98059, a specific inhibitor of p44/42 MAPK. Monocyte/macrophages challenged with titanium particles also showed a time-dependent activation of AP-1, a transcription factor associated with VEGF expression (p < 0.01). Supernatants from particle-challenged monocyte/macrophages increased macrophage chemotactic activity by 30%, which was significantly inhibited by anti-VEGF neutralizing antibody (p < 0.01).This study suggests that induction of VEGF release from monocyte/macrophages in response to orthopaedic biomaterial wear debris may contribute to periprosthetic osteolysis and implant loosening.
View details for Web of Science ID 000184943900003
View details for PubMedID 12968666
Wear particles generated after total joint arthroplasty activate monocyte/macrophages and incite formation of a granulomatous periprosthetic tissue associated with bone loss and implant loosening. This study tested the hypothesis that selective opsonization of orthopedic implant biomaterial wear particles by human serum proteins influences monocyte/macrophage activation. Serum protein binding to metallic, polymeric, and ceramic particles was determined by one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Individual proteins bound to particles were subsequently identified using two-dimensional SDS-PAGE, microsequencing techniques, and SWISS-PROT analysis. Effects of selective protein opsonization on particle-induced monocyte/macrophage activation were assessed by quantification of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha release. Results from one-dimensional gel analyses revealed distinct serum protein-binding patterns specific for each material tested. Two-dimensional gel analysis together with amino acid sequencing of the prominent protein species confirmed the presence of albumin and alpha-1-antitrypsin bound to all particles tested. In contrast to the metallic particles, apolipoprotein was a major species associated with polymeric particles. Opsonization of PMMA particles with purified preparations of each of the identified proteins showed that albumin significantly enhanced particle-induced monocyte/macrophage activation. These data confirm orthopedic biomaterial specific binding of human serum proteins and demonstrate that albumin exacerbates particle-induced monocyte/macrophage activation. Alterations in the chemical and surface properties of orthopedic biomaterials to modulate protein interactions may improve implant longevity.
View details for DOI 10.1002/jbm.a.10477
View details for Web of Science ID 000182627600022
To test the effects of intermittent hydrostatic pressure (IHP) on nitric oxide (NO) release induced by shear stress and matrix macromolecule gene expression in human osteoarthritic chondrocytes in vitro.Chondrocytes isolated from cartilage samples from 9 patients with osteoarthritis were cultured and exposed to either shear stress or an NO donor. Nitrite concentration was measured using the Griess reaction. Matrix macromolecule mRNA signal levels were determined using reverse-transcriptase polymerase chain reaction and quantified by imaging analysis software.Exposure to shear stress upregulated NO release in a dose and time-dependent manner. Application of IHP inhibited shear stress induced NO release but did not alter NO release from chondrocytes not exposed to shear stress. Shear stress induced NO or addition of an NO donor (sodium nitroprusside) was associated with decreased mRNA signal levels for the cartilage matrix proteins, aggrecan, and type II collagen. Intermittent hydrostatic pressure blocked the inhibitory effects of sodium nitroprusside but did not alter the inhibitory effects of shear stress on cartilage macromolecule gene expression.Our data show that shear stress and IHP differentially alter chondrocyte metabolism and suggest that a balance of effects between different loading forces preserve cartilage extracellular matrix in vivo.
View details for Web of Science ID 000180709700022
View details for PubMedID 12563690
Patients with anterior cruciate ligament instability resulting from incomplete tears or elongation in continuity without ligament detachment historically have been treated conservatively or by graft replacement. The literature is sparse regarding alternative treatments. The current study presents experience using monopolar thermal repair on 28 consecutive knees with partial anterior cruciate ligament tears all symptomatically unstable. All lesions were less than 6 months old (average, 77 days; range, 7-180 days) and with a difference of 6 mm or more (average, 9 mm; range, 6-13 mm) when comparing both knees using KT-1000 evaluation. Incomplete tears of the anterior cruciate ligament were seen at arthroscopic evaluation. The rehabilitation protocol included use of a brace for at least 6 weeks and progressive weightbearing. A 2-year minimum followup (range, 24-35 months) was done in all patients following the International Knee Documentation Committee guidelines. The overall outcome was normal or nearly normal in 96% of the patients. One failure occurred at 8 weeks. Twenty-six knees had a KT-1000 difference between 0 and 2 mm (average, 1.9 mm). Because thermal application causes death to some of the cells directly treated, it should be taken into account in selection and application. Immediately after thermal use, the anterior cruciate ligament, although thicker and tighter, is at first weaker than normal. Rehabilitation and compliance are critical during early ligament healing. This procedure seems to be a reasonable alternative to anterior cruciate ligament grafting in selected patients.
View details for DOI 10.1097/01.blo.0000043053.62337.de
View details for Web of Science ID 000180878600021
View details for PubMedID 12567140
Complications in total knee arthroplasty directly related to hardware failure other than polyethylene wear are rare. We report 2 cases of symptomatic screw migration into the joint space from total knee prostheses. In the first case, a screw disengaged from a constrained condylar knee prosthesis. Arthroscopy using standard arthroscopy portals and a small arthrotomy were performed to remove the screw. In the second case, symptomatic screw disengagement and posterior migration from the tibial component of a posterior-stabilized prosthesis occurred. Revision with replacement of the polyethylene insert and locking screw was required.
View details for DOI 10.1054/arth.2002.34827
View details for Web of Science ID 000178462200022
View details for PubMedID 12375258
A review of postoperative infected anterior cruciate ligament reconstructions was done on 3500 consecutive arthroscopic procedures. The purpose was to assess incidence, diagnosis, treatment, and outcome factors. Six postoperative intraarticular infections were detected. Average followup was 3 years (range, 2-8 years). The rate of infection was 0.14%. Five men and one woman with a median age of 32.5 years (range, 20-51 years) comprised the study group. The average interval from the onset of symptoms to the initial arthroscopic intervention was 7.5 days (range, 2-20 days). Staphylococcus aureus was present in three knees, Staphylococcus epidermidis in two, and Streptococcus nonhemolytic in one. All patients had initial arthroscopic debridement and lavage followed by 6 weeks of intravenous antibiotics. Two grafts were removed: one patient had delayed ligament reconstruction and the other had total knee arthroplasty. The remaining patients had full range of motion. In the group with the best result, two patients had Staphylococcus epidermidis and one had Staphylococcus aureus, which was treated 2 days after clinical symptoms began. The other two patients infected with Staphylococcus aureus had unsatisfactory results. Anterior cruciate ligament infection is rare, but diagnosable. When treated early with appropriate antibiotic therapy and arthroscopic debridement, four of six grafts were retained. If the infection does not respond rapidly to early therapy, then graft removal is an option.
View details for Web of Science ID 000175433600027
View details for PubMedID 11964649
Harris-Galante modular acetabular components (Zimmer, Warsaw, IN) have been used widely for primary and revision total hip arthroplasties. The survivorship of this implant has been well documented in the literature. Failure of the liner locking mechanism and subsequent dissociation of the polyethylene liner from the metal-backed shell is a potential cause of failure, however. We report 7 cases of liner dissociation and propose the mode of failure. The result in all cases was a well-fixed metal acetabular shell with a failed locking mechanism, which usually is managed by revision of the entire component. This procedure may be accompanied by the potential loss of acetabular bone stock, which should be replenished.
View details for Web of Science ID 000173522800012
View details for PubMedID 11805929
Perioperative knee mechanics currently are evaluated Perioperative knee mechanics currently are evaluated by measuring range of motion. This is an incomplete measurement, however, because the torque applied to achieve the motion is not measured. We hypothesized that a custom goniometer and force transducer could measure the torque required to passively flex a knee through its full range of motion. This measurement was done in the operating room immediately before and after surgery in 20 knees having total knee arthroplasty and 9 having surgery on another limb. Surgery changed the mechanics of 8 knees, whereas unoperated knees remained unchanged. This measurement technique is safe, easy, and repeatable. It improves on the current standard of perioperative knee measurement and can be applied to investigate the effects of surgery and rehabilitation on ultimate knee motion.
View details for Web of Science ID 000171577100010
View details for PubMedID 11607904
Periprosthetic membranes commonly observed at sites of total joint implant loosening exhibit abundant macrophages and particulate debris. Macrophages phagocytose orthopedic debris and release the pro-inflammatory mediators interleukin-1, interleukin-6, tumor necrosis factor-alpha, and prostaglandin E2. Populations of activated lymphocytes are often seen in periprosthetic membranes. These lymphocytes may modulate the monocyte/macrophage response to particulate debris and influence aseptic loosening. In addition, other immunologic agents, such as interleukin-10, are present in tissues harvested from the bone-implant interface of failed total joint arthroplasties. The present study examined the effects of interleukin-10 on polymethylmethacrylate (PMMA) particle challenged human monocyte/macrophages in vitro. Human monocyte/macrophages isolated from buffy coats of five healthy individuals were exposed to 1-10 microm PMMA particles. Interleukin-10 was added to the monocyte/macrophages with and without the addition of PMMA particles. Interleukin-10-induced alterations in monocyte/macrophage metabolism were determined measuring interleukin-6 and tumor necrosis factor-alpha release by the cells following exposure to PMMA particles. Exposure of the monocyte/macrophages to PMMA particles resulted in a dose-dependent release of interleukin-6 and tumor necrosis factor-alpha at 48 h. Interleukin-10 reduced the levels of interleukin-6 and tumor necrosis factor-alpha release by macrophages in response to PMMA particles in a dose-dependent manner. At 48 h, particle-induced interleukin-6 release was inhibited by 60 and 90% with 1.0 and 10.0 ng/ml treatments of interleukin-10, respectively. At 48 h, particle-induced tumor necrosis factor-alpha release was inhibited by 58 and 88% with 1.0 and 10.0 ng/ml treatments of interleukin-10, respectively. Interleukin-10 challenge alone did not significantly alter basal interleukin-6 or tumor necrosis factor-alpha release relative to control cultures. The data presented in this study demonstrate that the anti-inflammatory cytokine, interleukin-10, inhibits monocyte/macrophage release of the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha in response to PMMA particle challenge in vitro.
View details for Web of Science ID 000169365300001
View details for PubMedID 11432585
Periprosthetic tissues observed at sites of loose total joint implants exhibit abundant macrophages, lymphocytes, fibroblasts and particulate debris. Macrophages phagocytose orthopaedic debris and release proinflammatory cytokines, chemokines, matrix metalloproteinases and other substances. In addition, other cell types present in tissues harvested from the bone-implant interface are thought to influence periprosthetic bone resorption. The present study examined the effects of polymethylmethacrylate (PMMA), cobalt chrome molybdenum alloy (CoCr), and titanium-alloy particle challenge on macrophages co-cultured with lymphocytes in vitro. Potential synergistic effects of lymphocytes on macrophage activation were determined by measuring interleukin-6 and tumor necrosis factor-alpha release following exposure to orthopaedic biomaterial particles. Exposure of macrophages or macrophages co-cultured with lymphocytes to all three types of particles resulted in increased release of interleukin-6 and tumor necrosis factor-alpha at 48 h, when compared to macrophages or macrophages co-cultured with lymphocytes, respectively, cultured in the absence of particles. Lymphocytes isolated from periprosthetic tissues secreted increased basal levels of cytokines relative to peripheral blood lymphocytes. Higher doses of PMMA and titanium-alloy particles stimulated increased levels of cytokine release in the macrophage and macrophage/lymphocyte groups. In contrast, a higher dose of CoCr particles (0.075% v/v) was not as effective as the 0.015% v/v dose, indicating probable CoCr toxicity. The macrophage/lymphocyte co-culture did not show synergism between the two types of cells with respect to cytokine release. T-cells at the bone-implant interface may alter the biological response to particulate debris.
View details for Web of Science ID 000166303300008
View details for PubMedID 11197500
Periprosthetic granulomatous membranes consisting of fibroblasts, macrophages, lymphocytes, foreign body giant cells, and abundant particulate debris occur at sites of implant loosening. Previous studies demonstrate that fibroblasts respond to particulate debris through the release of interleukin-6 (IL-6), prostaglandin E(2), and matrix metalloproteinases in vitro. C-C chemokines are observed in granulomatous tissue surrounding loosened prosthetic implants and are released by macrophages and fibroblasts in response to particle challenge in vitro. This study tested the hypothesis that G protein activity is required for fibroblast activation by titanium and polymethylmethacrylate (PMMA) particles, and that inhibition of G protein activity would alter IL-6 and and monocyte chemoattractant protein-1 (MCP-1) release from activated fibroblasts. The specific inhibitor of G protein activity, pertussis toxin, was added to the fibroblasts to examine the effects of G protein activity with respect to the production of IL-6 and MCP-1 by orthopedic biomaterial-challenged fibroblasts in vitro. Interleukin-1beta (IL-1beta), a proven activator of MCP-1 and interleukin-6, was used as a positive control. Exposure of fibroblasts to titanium and polymethylmethacrylate (PMMA) particles resulted in a dose-dependent release of MCP-1 and IL-6. Challenge with PMMA particles at doses of 0.150%, 0.300%, and 0.600% vol/vol increased the release of interleukin-6 by 7-, 19-, and 22-fold, respectively, compared to fibroblasts exposed to serum-free culture medium alone at 24 h. Challenge with PMMA particles at doses of 0.075%, 0.150%, 0.300%, and 0.600% vol/vol increased the release of MCP-1-6 by 2.5-, 3.6-, 4. 3-, and 4.5-fold, respectively, compared to fibroblasts exposed to serum-free culture medium alone. Challenge with titanium particles at concentrations of 0.075%, 0.150%, 0.300%, and 0.600% vol/vol increased the release of interleukin-6 by 2.6-, 6.4-, 9.6-, and 10. 0-fold, respectively, compared to fibroblasts exposed to serum-free culture medium alone at 24 h. Challenge with titanium particles at concentrations of 0.038%, 0.075%, 0.150%, 0.300%, and 0.600% vol/vol increased the release of MCP-1 by 2.9-, 3.1-, 5.8-, 5.4-, and 5. 8-fold, respectively, compared to fibroblasts exposed to serum-free culture medium alone. Pretreatment of fibroblasts with pertussis toxin inhibited the release of interleukin-6 and MCP-1 from PMMA and titanium particle challenged fibroblasts in a dose-dependent manner. PMMA particle induced fibroblast IL-6 release was inhibited by 23.6% and 35.3% with 20- and 200-ng/mL doses of pertussis toxin, respectively. Titanium particle induced fibroblast IL-6 release was inhibited by 48.2% and 56.3% with 20- and 200-ng/mL doses of pertussis toxin, respectively. PMMA particle-induced fibroblast MCP-1 release was inhibited by 36.0%, 50.4%, and 60.1% with 2-, 20- and 200-ng/mL doses of pertussis toxin, respectively. Titanium particle-induced fibroblast MCP-1 release was inhibited by 15.5%, 53.2%, and 64.6% with 2-, 20-, and 200-ng/mL doses of pertussis toxin, respectively. This study suggests that fibroblasts localized in periprosthetic membranes are a source of macrophage chemoattractant factors and proinflammatory mediators that may influence granuloma formation and lead to periprosthetic bone resorption. Furthermore, this study shows that G proteins are involved in particle-induced fibroblast activation, as evidenced by decrease levels of particle induced IL-6 and MCP-1 release following pertussis toxin treatment. (c) 2000 John Wiley & Sons, Inc.
View details for Web of Science ID 000087914500009
View details for PubMedID 10880077
Orthopaedic wear debris induces release of bone-resorbing factors from macrophages and fibroblasts. However, the extent to which elemental metallic particles induce bone cells to express factors contributing to implant loosening remains unclear. This study showed that exposure of MG-63 osteoblast-like cells to titanium particles at a concentration of 0.30% v/v resulted in a 15-fold increase in IL-6 release into the culture medium after 24 hours, when compared with cells without particles. Northern blots revealed that exposure of MG-63 cells to titanium particles at a concentration of 0.30% v/v for 24 hours increased IL-6 mRNA signal levels by 9.6-fold, when compared with control cultures. Pretreatment of MG-63 cells with cytochalasin B prevented the particle-induced increase of IL-6 expression but did not alter the basal level of IL-6 release from cells cultured in the absence of particles. The protein kinase C inhibitor, H7, and the serine/threonine kinase inhibitor, genistein, abolished the particle-induced increase in IL-6 release at a concentration of 100 microM for each compound. In contrast, an inhibitor of protein kinase A, HA1004, had no effect on the particle-induced increase in IL-6 release. The transcription factors, nuclear factor IL-6 and nuclear factor kappa B, translocated into the nucleus within 1 hour of particle exposure. This study showed that osteoblast-like cells respond to titanium particles through increased expression of the proinflammatory cytokine, IL-6, in a process requiring phagocytosis and intracellular signaling pathways. These results suggest that osteoblasts play a direct role in implant loosening because of localized release of soluble mediators such as interleukin-6.
View details for Web of Science ID 000088387400010
View details for PubMedID 10920220
Periprosthetic membranes commonly observed at sites of total joint implant loosening exhibit abundant macrophages and particulate debris. Macrophages phagocytose orthopedic debris and release the pro-inflammatory mediators interleukin-1, interleukin-6, tumor necrosis factor-alpha, and prostaglandin E2. In addition, other immunologic agents, such as interferon-gamma, are present in tissues harvested from the bone-implant interface of failed orthopedic implants. The present study examined the effects of interferon-gamma on polymethylmethacrylate (PMMA) particle-challenged monocyte/macrophages in vitro. The effects of interferon-gamma were determined by measuring interleukin-6 and tumor necrosis factor-alpha release by primary human monocyte/macrophages following exposure to PMMA particles. Exposure of the monocyte/macrophages to PMMA particles resulted in a dose-dependent release of interleukin-6 and tumor necrosis factor-alpha at 48 h. The interleukin-6 release in response to PMMA particle challenge was stimulated by 76% and 127% in the presence of 1.0 and 10.0 ng/mL of interferon-gamma, respectively. Interferon-gamma challenge alone did not alter interleukin-6 release relative to controls. In contrast to interleukin-6, interferon-gamma challenge stimulated tumor necrosis factor-alpha release in a dose-dependent manner. In the presence of particles, addition of 1.0 and 10.0 ng/mL of interferon-gamma resulted in 17% and 171% increases in the levels of tumor necrosis factor-alpha release, respectively, relative to cultures challenged solely with particles. Blocking antibody to IFN-gamma inhibited the effect of IFN-gamma on particle-induced interleukin-6 and tumor necrosis factor-alpha release. The data presented in this study demonstrate that the immunologic modulator interferon-gamma exacerbates monocyte/macrophage release of the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha in response to PMMA particle challenge in vitro.
View details for Web of Science ID 000081599800001
View details for PubMedID 10400874
Cytokines that regulate monocyte migration were found in membrane tissue surrounding loosened prosthetic implants. Monocyte migration inhibition factor (MIF) is able to inhibit macrophage migration. Monocyte chemoattractant protein (MCP) and macrophage inflammatory protein (MIP) are potent macrophage chemoattractants. These cytokines may be expressed as part of the foreign body response to prosthetic particulate debris. Chemotaxis analysis and macrophage activation experiments were performed to determine the effects of MIF, MCP-1, and MIP-1alpha on macrophage migration and activation in vitro. We demonstrated that MIF had its maximal migration inhibitory effect for unchallenged and particle challenged macrophages at 1 ng/mL. MCP-1 and MIP-1alpha stimulated macrophage chemotaxis maximally at 1 to 10 ng/mL. Dose-response studies with MIF, MCP-1, and MIP-1alpha demonstrated that these cytokines did not modulate activation of unchallenged or particle challenged macrophages as evaluated by IL-6 and TNF-alpha release. However, these cytokines do not appear to affect macrophage release of proinflammatory mediators in vitro.
View details for Web of Science ID 000080480900007
View details for PubMedID 10398027
Loosening of the implant after total joint arthroplasty remains a serious problem. The activation of macrophages by wear debris from implants, mediated by the release of cytokines that elicit bone resorption, may lead to loosening. The purpose of the present study was to elucidate the mechanisms of macrophage activation by titanium particles from the components of implants and to identify the signaling pathways involved in particle-mediated release of cytokines.Macrophages were isolated from mononuclear leukocytes obtained from healthy human donors and were exposed to titanium-alloy particles that had been obtained from periprosthetic membranes collected at revision total joint arthroplasties and then enzymatically prepared. The experimental protocols included examination of the effects of the inhibition of phagocytosis and the binding of antibodies to macrophage complement receptors on particle-induced macrophage activation. The release of the proinflammatory cytokines TNF-alpha (tumor necrosis factor-alpha) and IL-6 (interleukin-6) was used to assess macrophage activation. The signaling pathways involved in the induction of cytokine release were analyzed by identification of phosphorylated proteins with use of the Western blot technique and by translocation of the transcription factors nuclear factor-kappa B (NF-kappaB) and nuclear factor-interleukin-6 (NF-IL-6) into the nuclear protein fraction with use of electrophoretic mobility shift assays. The role of serine/threonine and tyrosine kinase pathways in the activation of nuclear factors and the release of cytokines was examined with use of selective pharmacological agents.Exposure of macrophages to titanium-alloy particles in vitro for forty-eight hours resulted in a fortyfold increase in the release of TNF-alpha and a sevenfold increase in the release of IL-6 (p<0.01). Phagocytosis of particles occurred in approximately 73 percent of the macrophages within one hour of exposure. Pretreatment of the macrophages with cytochalasin B reduced phagocytosis by 95 percent but did not reduce the release of TNF-alpha or IL-6. Thus, phagocytosis of particles was not necessary for induction of the release of TNF-alpha or IL-6 in the cultured macrophages. Ligation of the macrophage CD11b/CD18 receptors by integrin-specific antibodies also increased the release of TNF-alpha and IL-6. Antibodies to CD11b/ CD18 receptors (macrophage Mac-1 receptors) reduced phagocytosis of particles by 50 percent (p<0.05). (The CD11b/CD18 macrophage receptor is the macrophage receptor for the complement component CR3bi. The CD11b/CD18 macrophage receptor can also bind to ICAM-1 and ICAM-2. CD is the abbreviation for cluster of differentiation, and ICAM is the abbreviation for intercellular adhesion molecule.) Inhibition of phagocytosis was not accompanied by a decrease in the release of TNF-alpha and IL-6. Blocking RNA synthesis with actinomycin D or preventing protein synthesis with cycloheximide abolished or decreased particle-induced release of TNF-alpha and IL-6 from the macrophages. Macrophage release of TNF-alpha and IL-6 in response to particles coincided with increased tyrosine phosphorylation and mitogen-activated protein kinase activation. Inhibition of tyrosine and serine/threonine kinase activity decreased the particle-induced release of cytokines. Exposure of macrophages to either titanium-alloy particles or to antibodies to the receptor proteins CD11b and CD18 for thirty minutes activated the transcription factors NF-kappaB and NF-IL-6. Inhibition of particle phagocytosis did not block activation of the transcription factors. However, inhibition of tyrosine and serine/threonine kinase activity decreased the activation of NF-kappaB and NF-IL-6.These data suggest that particle induced macrophage release of TNF-alpha and IL-6 does not require phagocytosis but is dependent on tyrosine and serine/threonine kinase activity culminating in activation of
View details for PubMedID 10360689
Particulate wear debris is associated with periprosthetic inflammation and loosening in total joint arthroplasty. We tested the effects of titanium alloy (Ti-alloy) and PMMA particles on monocyte/macrophage expression of the C-C chemokines, monocyte chemoattractant protein-1 (MCP-1), monocyte inflammatory protein-1 alpha (MIP-1alpha), and regulated upon activation normal T expressed and secreted protein (RANTES). Periprosthetic granulomatous tissue was analysed for expression of macrophage chemokines by immunohistochemistry. Chemokine expression in human monocytes/macrophages exposed to Ti-alloy and PMMA particles in vitro was determined by RT-PCR, ELISA and monocyte migration. We observed MCP-1 and MIP-1alpha expression in all tissue samples from failed arthroplasties. Ti-alloy and PMMA particles increased expression of MCP-1 and MIP-1alpha in macrophages in vitro in a dose- and time-dependent manner whereas RANTES was not detected. mRNA signal levels for MCP-1 and MIP-1alpha were also observed in cells after exposure to particles. Monocyte migration was stimulated by culture medium collected from macrophages exposed to Ti-alloy and PMMA particles. Antibodies to MCP-1 and MIP-1alpha inhibited chemotactic activity of the culture medium samples. Release of C-C chemokines by macrophages in response to wear particles may contribute to chronic inflammation at the bone-implant interface in total joint arthroplasty.
View details for PubMedID 10068024
Postoperative knee flexion in patients undergoing Insall-Burstein-II total knee arthroplasty at 2 years was evaluated regarding two basic questions: what groups of patients gain or lose the most flexion and what groups of patients have the best or worst postoperative flexion. Thirteen preoperative variables (maximum flexion, flexion arc, tibiofemoral angle, quadriceps strength, extensor lag, Knee Society score, Knee Society patient assessment, gender, age, height, weight, diagnosis, and surgeon) and four postoperative variable (leg length change, tibiofemoral angle, distance from patella to the joint line, and the tibial prosthesis anteroposterior translation on a lateral radiograph) were used in an attempt to explain postoperative flexion. The analysis was performed on 164 consecutive Insall-Burstein-II total knees in which the data were gathered prospectively on a time oriented medical record database. A regression tree analysis was used to identify several groups of patients, characterized by preoperative factor values, who had markedly above average performance on postoperative flexion. The preoperative factors identified include preoperative flexion, flexion arc, tibiofemoral angle, extensor lag, diagnosis, and age. The only postoperative variable of significance was tibiofemoral angle. Among the potential determinants of postoperative flexion that failed to appear predictive were the Knee Society scores and surgeon. Preoperative flexion is known to be a critical determinant of postoperative flexion in total knee replacement. However, in the current study, preoperative flexion accounted for only half of the difference between the best (122 degrees) and the worst (88 degrees) group, as determined with regression tree analysis.
View details for Web of Science ID 000075541700020
View details for PubMedID 9728172
We exposed human macrophages isolated from the peripheral blood of healthy donors to metal and bone-cement particles from 0.2 to 10 microm in size. Zymography showed that macrophages exposed to titanium alloy and polymethylmethacrylate (PMMA) particles released a 92- and 72-kDa gelatinase in a dose- and time-dependent manner. Western immunoblotting confirmed that the 92- and 72-kDa gelatinolytic activities corresponded to matrix metalloproteinase-9 and matrix metalloproteinase-2 (MMP-9, MMP-2), respectively. Western immunoblotting also indicated that titanium alloy and PMMA particles increased the release of MMP-1. Northern blotting showed elevated mRNA signal levels for MMP-1, MMP-2, and MMP-9 after exposure to both types of particle. Collagenolytic activity also increased in the macrophage culture medium in response to both types of particle. Our findings support the hypothesis that macrophages release MMPs in proportion to the amount of particulate debris within periprosthetic tissues.
View details for PubMedID 9699840
The condylar constrained total knee arthroplasty was performed on 29 patients undergoing 33 procedures and were reviewed clinically and radiographically at an average follow-up of 5 years (range, 2-10 years). There were 21 women and 8 men. The average age at the time of surgery was 70 years (range, 32-84). Of the 16 knees that were revision total knee arthroplasties, 8 had a previous infected total knee arthroplasty, and 17 knees had severe deformities requiring the use of the condylar constrained prosthesis. The patients were rated according to the Knee Society clinical and radiological evaluation protocol. Measurements of femoral and tibial component position were obtained as well as femoral tibial angle, patella position, and cement bone radiolucencies. All clinical measurements were made by an independent physical therapist. Clinical results revealed an improvement from an average preoperative knee score of 38 points to an average postoperative score of 86 points. The clinical results for 19 (58%) knees were excellent, 8 (24%) had a good result, 1 (3%) was fair, 2 (6%) were poor, and 3 (9%) were failures. The patients' average functional levels increased from 24 to 58. The final average flexion was 96 degrees. Three knees have been revised (9%). One was revised for recurrent infection, one for periprosthetic fracture, and one for mechanical loosening of the tibial component. There were no other knees with evidence of radiologic loosening. We conclude that the condylar constrained total knee prosthesis provides an acceptable solution for revision and complex primary total knee replacements at an intermediate follow-up term of 5 years.
View details for Web of Science ID 000074132700003
View details for PubMedID 9645517
View details for PubMedID 9771535
The tissues surrounding 65 cemented and 36 cementless total joint replacements undergoing revision were characterised for cell types by immunohistochemistry and for cytokine expression by in situ hybridisation. We identified three distinct groups of revised implants: loose implants with ballooning radiological osteolysis, loose implants without osteolysis, and well-fixed implants. In the cemented series, osteolysis was associated with increased numbers of macrophages (p = 0.0006), T-lymphocyte subgroups (p = 0.03) and IL-1 (p = 0.02) and IL-6 (p = 0.0001) expression, and in the cementless series with increased numbers of T-lymphocyte subgroups (p = 0.005) and increased TNF alpha expression (p = 0.04). For cemented implants, the histological, histochemical and cytokine profiles of the interface correlated with the clinical and radiological grade of loosening and osteolysis. Our findings suggest that there are different biological mechanisms of loosening and osteolysis for cemented and cementless implants. T-lymphocyte modulation of macrophage function may be an important interaction at prosthetic interfaces.
View details for Web of Science ID 000073647500031
This study evaluated the effects of combining antibiotic therapy with the application of a nonsteroidal anti-inflammatory drug on the degradation of articular cartilage for an animal model of Staphylococcal septic arthritis. Rabbits were infected intra-articularly with Staphylococcus aureus. Antibiotic treatment started 18 hours after infection and continued for 7 days. Treatment with the nonsteroidal anti-inflammatory drug naproxen sodium started 24 hours before infection and continued for either 3 or 7 weeks. The cartilage matrix of uninfected and infected knees was quantified by analysis of glycosaminoglycan and collagen content. Three weeks after infection, the combined treatment of the nonsteroidal anti-inflammatory drug and antibiotics reduced the loss of glycosaminoglycan and collagen from the cartilage of the infected knee by 15 and 30%, respectively, compared with antibiotic treatment alone. Continuing treatment with naproxen sodium for 7 weeks reduced the loss of collagen by 50% when compared with antibiotic treatment alone. The longer period of treatment with naproxen sodium showed little further effect on the loss of glycosaminoglycan than that observed for the 3-week treatment. Treatment with this drug and antibiotics reduced swelling of the knee and levels of prostaglandin E2 in the synovial fluid. The data support the hypothesis that decreasing post-infectious inflammation by adding the drug to a standard antibiotic regimen reduces cartilage damage from Staphylococcal septic arthritis.
View details for Web of Science ID 000072261300018
View details for PubMedID 9497819
The purpose of this study was to characterize the cell types (using immunohistochemistry) and cytokine expression (using in situ hybridization) of tissues surrounding well fixed and loose cemented prostheses undergoing revision. Clinical and radiographic data were gathered prospectively for a series of cemented total joint replacements undergoing revision. Three groups were identified: (1) loose implants with osteolysis (10 specimens), (2) loose implants without osteolysis (11 specimens), and (3) well fixed implants (7 specimens). At surgery, a specimen was harvested from the bone cement interface. Immunohistochemical staining was performed using monoclonal antibodies to identify macrophages and lymphocyte subgroups. Human antisense probes were selected to identify the mRNA for specific cytokines using in situ hybridization. The percentage of positively staining cells was determined for each antibody or probe using a grid counting technique. Tissues from loose cemented prostheses with osteolysis contained significantly greater numbers of macrophages and T lymphocytes compared with tissues from loose and well fixed cemented prostheses without osteolysis. The number of interleukin-1 and interleukin-6 positive cells was highest in specimens with osteolysis and lowest in specimens from well fixed prostheses. These cytokines modulate the growth and differentiation of cells in the immune system and the monocyte and macrophage system and mediate the remodeling of bone and mesenchymal tissues. Specific cell populations and cytokine profiles appear to be involved in periprosthetic osteolysis; this information may be useful in planning strategies for prevention and treatment.
View details for Web of Science ID A1997WT70700017
View details for PubMedID 9137186
The pneumatic tourniquet produces ischemic changes in limbs. The effects of tourniquet release on systemic blood pressure and metabolic parameters were studied in 11 adult patients undergoing total knee replacement under general anesthesia. Mean arterial pressure (MAP) decreased rapidly after the release of the tourniquet, becoming significant at 3 min and remaining significantly depressed up to 15 min post release. Arterial pH, PaO2, PaCO2, lactate acid, and potassium changed significantly after the release, but normalized within 30 min. These results are notably different from a previous study in a similar patient population undergoing knee replacement under epidural anesthesia. Compared to patients under epidural anesthesia, patients receiving general anesthesia with mechanical ventilation are unable to compensate for the metabolic load caused by the tourniquet release, as the latter group are unable to alter their ventilatory rate. In elderly patients with decreased cardio-pulmonary reserve, this may be of clinical importance.
View details for Web of Science ID A1996VY70500012
View details for PubMedID 8986188
A consecutive series of 49 patients who had a primary total hip arthroplasty (THA) for osteoarthritis is reviewed to determine the difference in clinical outcome between the direct lateral and the posterior surgical approaches to the hip. Group 1 comprised 28 patients off had THA by the same surgeon using a posterolateral approach. Group 2 comprised 21 patients who had THA using the direct lateral approach, modified from Hardinge. The improvement in the limp, abductor strength, Trendelenburg test, and range of motion over time was similar in the two groups. The average Harris hip score at 1 year was 90 for Group 1 (posterior approach) and Group 2 (lateral approach). At 2-year minimum follow up, the Harris hip score was 94 for both groups. Radiographic review showed that the incidence and severity of heterotopic bone was also similar for both groups. The authors conclude that the clinical and radiographic outcome for THA using the posterior and the lateral approaches to the hip yield similar clinical results.
View details for Web of Science ID A1996VN77400011
View details for PubMedID 8905861
Osteoarthritis is a disease in which articular cartilage metabolism is altered, leading to cartilage destruction. As insulin-like growth factor-I (IGF-I) is the major anabolic mediator for articular cartilage, and the IGF-binding proteins (IGFBPs) are an integral part of the IGF axis, they may play a role in the pathophysiology of osteoarthritis. Chondrocytes isolated from fibrillated and normal appearing areas of osteoarthritic human cartilage and from normal cartilage were studied for IGF and IGFBP expression. IGF and IGFBP messenger ribonucleic acids were analyzed by a RT-quantitative PCR technique and Northern blotting. In osteoarthritic chondrocytes, IGF-I message was increased 3.5-fold, IGFBP-3 was increased 24-fold, and IGFBP-5 was increased 16-fold over normal chondrocytes. Chondrocytes from normal appearing areas of cartilage from osteoarthritic joints had intermediate levels. Message levels for beta-actin, IGF-II, and IGFBP-4 were unchanged between the cartilage types. IGF and IGFBP production were analyzed by Western ligand blots and RIAs of conditioned medium from cartilage cultured in serum-free conditions. IGF-I was undetectable in conditioned medium from normal cartilage and increased in that from osteoarthritic cartilage. Osteoarthritic cartilage samples produced IGFBP-2, -3, and -4; glycosylated IGFBP-4; and IGFBP-5. IGFBP-2, -3, and -5 production was increased in osteoarthritic cartilage. Proteases with activity against IGFBP-3 and -5 were also produced by osteoarthritic cartilage. The observation that IGFBP-3 and -5 expression and production are elevated in osteoarthritic cartilage suggests that they may be acting as a competitor for IGF-I in osteoarthritic cartilage, thus reducing the anabolic stimulation of this tissue and contributing to the net loss of cartilage in this disease.
View details for Web of Science ID A1996TZ90600042
View details for PubMedID 8772582
This study tested the effects of hydrostatic pressure (10 MPa) on adult articular chondrocyte mRNA and extracellular matrix synthesis in vitro. High density primary cultures of bovine chondrocytes were exposed to hydrostatic pressure applied intermittently at 1 Hz or constantly for 4 hours in serum-free medium or in medium containing 1% fetal bovine serum. mRNAs for aggrecan, types I and II collagen, and beta-actin were analyzed by Northern blots and quantified by slot blots. Proteoglycan synthesis was quantified by 35SO4 uptake into cetylpyridinium chloride-precipitable glycosaminoglycans, and cell-associated aggrecan and type-II collagen were detected by immunohistochemical techniques. In serum-free medium, intermittent pressure increased aggrecan mRNA signal by 14% and constant pressure decreased type-II collagen mRNA signal by 16% (p < 0.05). In the presence of 1% fetal bovine serum, intermittent pressure increased aggrecan and type-II collagen mRNA signals by 31% (p < 0.01) and 36% (p < 0.001), respectively, whereas constant pressure had no effect on either mRNA. Intermittent and constant pressure stimulated glycosaminoglycan synthesis 65% (p < 0.001) and 32% (p < 0.05), respectively. Immunohistochemical detection of cell-associated aggrecan and type-II collagen was increased in response to both intermittent and constant pressure. These data support the hypothesis that physiologic hydrostatic pressure directly influences the extracellular matrix metabolism of articular chondrocytes.
View details for Web of Science ID A1996UA58800009
View details for PubMedID 8618166
We report here that a 92-kD gelatinolytic metalloproteinase is expressed as protein and mRNA in human osteoarthritic cartilage, but not in normal adult articular cartilage. Western immunoblotting demonstrated that the 92-kD gelatinolytic activity corresponded to 92-kD type IV collagenase/gelatinase (gelatinase B); mRNA for gelatinase B was identified by Northern blotting. Chondrocytes from normal cartilage also exhibited mRNA for 72-kD type IV collagenase/gelatinase (gelatinase A), tissue collagenase, and stromelysin-1, and these mRNAs were increased in osteoarthritic cartilage. Regional analysis of osteoarthritic cartilage samples from four individuals revealed that gelatinase B mRNA was expressed in grossly fibrillated areas; two of four nonfibrillated cartilage samples failed to exhibit the mRNA, but did have increased levels of mRNA for other neutral metalloproteinases. IL-1 alpha treatment of normal human cartilage explants or isolated chondrocytes induced increased levels of gelatinase B and increased mRNA for tissue collagenase and stromelysin-1. Under identical conditions, mRNA levels for gelatinase A were not increased indicating that regulation of this enzyme in human articular chondrocytes is distinct from that of other metalloproteinases. Our data showing expression of gelatinase B in fibrillated cartilage suggest that it is a marker of progressive articular cartilage degradation in osteoarthritis.
View details for Web of Science ID A1993LL77300024
View details for PubMedID 8325982
Bovine synovial fibroblasts in primary monolayer culture were exposed to particulate metallic debris. The effects of the metallic particles on the synthesis and secretion of proteolytic enzymes and on cell proliferation and viability were examined. Uniform suspensions of titanium, titanium-aluminum, cobalt, and chromium particles, ranging in size from approximately 0.1 to ten micrometers (average, one to three micrometers), were prepared; the particle concentrations (the volume of particles divided by the total volume of the suspension) ranged from 0.0005 to 5 per cent. Aliquots of the particle suspensions were added to the synovial fibroblast cultures. The final particle concentrations in the media ranged from 0.0000083 to 0.83 per cent. After seventy-two hours of exposure, each medium was harvested and was assayed for proteolytic and collagenolytic activity and for hexosaminidase levels. Neutral metalloproteases, quantified by collagenolytic and caseinolytic (proteolytic) activity, represent enzymes, secreted by cells, that are capable of degrading extracellular matrix. Hexosaminidase is a marker for lysosomal enzyme activity that can include more than thirty enzymes, such as proteases, lipases, nucleases, and phosphatases. Cell proliferation was quantified by uptake of 3H-thymidine. Cell morphology was examined by scanning electron microscopy. Titanium, titanium-aluminum, and chromium significantly stimulated 3H-thymidine uptake at low particle concentrations (p < 0.01, p < 0.002, and p < 0.002, respectively). Exposure to cobalt, even at the lowest particle concentration, resulted in a significant decrease in thymidine uptake (p = 0.027). At the highest particle concentrations, all particles were toxic, as evidenced by the absence of thymidine uptake. At high particle concentrations, all of the metals caused a decrease in caseinolytic (proteolytic) and collagenolytic activity in the culture media. Titanium elevated the lysosomal enzyme marker, hexosaminidase, except at high concentrations. Chromium and titanium-aluminum had no significant effect on hexosaminidase at any particle concentration, while cobalt decreased all enzyme markers at mid-particle to high-particle concentrations. Scanning electron microscopy demonstrated that the morphological response of fibroblasts to titanium included membrane-ruffling and extension of filopodia, typical of active fibroblasts. In contrast, exposure to cobalt at the same concentration resulted in cell crenation, indicative of cell death.
View details for PubMedID 8314824
Cement removal in revision total hip arthroplasty can be technically challenging. Traditional methods involve using a combination of chisels, power burrs, and drills, as well as windowing the femoral cortex to gain access to cement distally. These methods can be associated with femoral fracture or uncontrolled cortical perforation and bone loss. A new technique had been developed that permits segmental extraction of bone cement from the femoral canal. Fresh cement is introduced into the old cement mantle and a threaded rod is placed into the wet cement and held in place while the cement hardens. The thread-forming rod is then removed leaving a threaded channel in the cement. Extraction rods are then screwed 1.5 to 2.5 cm into the threaded channel. A slap hammer, which attaches to the opposite end of the extraction rod, is used to remove 1.5- to 2.5-cm segments of cement. Fifteen cases involving revision of cemented femoral components were analyzed using this system. Complete cement removal was achieved in 12 cases with much less damage to the femur when compared with conventional methods. In two cases, there was retained cement along the medial wall of the femur and, in one case, the plug could not be extracted using this system. There were no fractures or cortical perforations in this series.
View details for Web of Science ID A1992KB63200021
View details for PubMedID 1446433
Range of motion (ROM) after total knee arthroplasty (TKA) is an important variable in determining clinical outcome. Recent design modifications have been aimed at improving final motion. The posterior stabilized total knee prosthesis was introduced as a modification of the total condylar design, changing the center of curvature of the femoral component to allow greater ROM. In this study, all primary TKAs performed at the authors' institution from July 1982 until December 1986 were reviewed to determine the effect of this design modification on outcome. A total condylar (TC) group comprised 51 arthroplasties and was compared to 53 arthroplasties in a posterior stabilized (PSTC) group. the postoperative protocol was identical in both groups. The mean postoperative flexion was 11 better in the PSTC group; however, the mean preoperative flexion had initially been 10 degrees better in the PSTC group. The maximum flexion achieved by any patient in both groups was similar, but the TC group actually gained slightly more arc of motion. The better motion in the PSTC group may be secondary to better motion preoperatively and not implant design in this series. The more limited the preoperative ROM, the greater the quadriceps stiffness is likely to be, which is an important determinant of postoperative flexion. Review of the literature supports present observations that a group with less mean preoperative motion paradoxically gains a slightly greater increment of flexion. Differences in flexion after TKA are difficult to attribute to design in either the current study or by a review of the literature. This is because determinants of flexion after TKA are multifactorial and outcome data limited, notwithstanding the similarities among modern prostheses.
View details for Web of Science ID A1992HR56200024
View details for PubMedID 1563146
This study analyzed processes underlying osteoporosis and osteoarthrosis after short-term immobilization of the right hind limb of postadolescent (2.8 kg) and mature (4.0 kg) rabbits. After 3 weeks, the lateral posterior aspect of the lateral tibial plateau and the lateral femoral condyle of the immobilized limb exhibited prominent subchondral vascular eruptions. Femoral metaphyseal bone density decreased 27 and 18% in the immobilized limbs of postadolescent and mature rabbits, respectively. Calcein green fluorescence increased 1.9-fold (p less than 0.001) in the metaphyseal trabeculae of immobilized femurs. With immobilization, sulfate incorporation into femoral cartilage glycosaminoglycan increased, although total cartilage glycosaminoglycan and hydroxyproline levels were unchanged. Thymidine incorporation into DNA increased four- to fivefold in tibial and femoral cartilage of the immobilized limb. In this study, bone loss and remodeling preceded erosive cartilage degradation.
View details for Web of Science ID A1992GX48200010
View details for PubMedID 1370179
Human articular cartilage released significantly increased levels of metal-dependent enzymes capable of degrading collagen, casein, and gelatin at a neutral pH following exposure to a sterile, purified fraction of Staphylococcus aureus culture medium. Neutral metalloprotease activity was determined by radiolabeled substrate assays and substrate gel analysis. The enzymes were activated with 4-aminophenylmercuric acetate and were inhibited by 1,10-phenanthroline and ethylenediamine tetraacetic acid. Protein immunoblots demonstrated that type I collagenase and stromelysin (matrix metalloproteinase III) secretion was increased following staphylococcal medium challenge. The profile of enzymatic activity induced by staphylococcal medium was directly comparable to that observed with interleukin-1, which was used as a positive control. The staphylococcal medium had no inherent proteolytic activity. Increased production of the neutral metalloproteases collagenase and stromelysin may significantly contribute to the extensive cartilage destruction noted in staphylococcal septic arthritis.
View details for Web of Science ID A1991EW65600013
View details for PubMedID 1846914
Can patients treated with total hip arthroplasty (THA) receive high-quality inpatient care at less cost? In 1984, a group of orthopedic surgeons and nurses examined the use of resources for THA patients and changed certain clinical practices to promote more cost-effective hospital care. At the end of the two-year project, orders for complete blood counts fell 72% and mean operating room time dropped 47 minutes for the participating orthopedists. For all orthopedists in the division, average length of stay (ALOS) decreased from 13 to 11 days. By the end of the following year, when clinicians received quarterly length-of-stay (LOS) data, ALOS dropped further to 9.8 days. This significant ALOS reduction was not accompanied by an increase in hospital readmissions or nursing home placements. The ALOS reduction was also not seen in elective coronary artery bypass graft patients whose ALOS did not substantially change over the same period. Two years after the project, ALOS for THA patients remained at ten days or below. This reduction in LOS and in the use of other hospital services translated into a mean total hospital charge decrease of $2045 per THA patient.
View details for Web of Science ID A1990DX99200021
View details for PubMedID 2394045
The relationship between adherence of bacteria to foreign bodies and their deposition of extracellular matrix was examined on glass and suture material. To quantitate bacterial adherence, uptake of [3H]thymidine into bacterial DNA was analyzed. Corresponding amounts of extracellular matrix were measured by a new technique using [14C]glucose incorporation. This study shows that [14C]glucose preferentially labeled bacterial strains in proportion to biofilm production. The ratio of 3H14C in high biofilm producers was 0.9 and in low producers it was 3.7. Radioactive identification of organisms as high and low producers was confirmed by electron microscopy. The results presented here show that production and accumulation of biofilm over time is a stable characteristic in different strains of S. epidermidis. The use of ratios reflecting radiolabeling of bacteria and biofilm by [3H]thymidine and [14C]glucose, respectively, is a quantitative yet simple technique to assess extracellular matrix of different strains of S. epidermidis.
View details for Web of Science ID A1990CZ95500002
View details for PubMedID 2324850
We report herein that cartilage proteolytic activity increased in bovine and rabbit articular cartilage after treatment with a purified staphylococcal culture medium or intraarticular infection with Staphylococcus aureus. Staphylococcal culture medium increased the release of gelatinolytic, collagenolytic, and caseinolytic activity into the medium of isolated chondrocytes or cartilage organ culture. The proteolytic activities were determined in assays using radiolabeled substrate and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Staphylococcal culture medium was proteolytically inactive by both assay techniques. RNA synthesis of isolated chondrocytes was unaffected by staphylococcal culture medium, whereas overall protein synthesis was inhibited by 84%. An analysis of extracts of Staphylococcus aureus-infected rabbit knee cartilage by substrate gels showed increased gelatinolytic and caseinolytic activity compared with extracts of uninfected knee cartilage. Our data suggest that the rapid loss of proteoglycan and persistent degradation of cartilage in staphylococcal septic arthritis is due to the production and activation of chondrocyte proteases.
View details for Web of Science ID A1990CZ97400011
View details for PubMedID 1691643
Seventeen nonconstrained total elbow replacements were inserted in 12 patients. One patient died prior to the one-year follow-up examination, and two others required revision in the immediate postoperative period. The remaining 14 primary total elbow arthroplasties in 11 patients were included in this study. There were eight women and three men with an average age of 58.1 years. The diagnosis was rheumatoid arthritis in 12 patients and posttraumatic arthritis and juvenile rheumatoid arthritis each in one patient. Postoperatively, patients were immobilized in a long arm cast. The mean hospital stay was 4.3 days. At four weeks, the patients were seen for cast removal. Instructions were given for range of motion (ROM) exercises and patients were encouraged to resume normal daily activities as tolerated. No formal physical therapy was prescribed. The average follow-up period was 32 months. Preoperatively, the mean elbow motions were flexion 124 degrees, extension 34 degrees, pronation 65 degrees, and supination 44 degrees. At the last follow-up examination, ROM had improved significantly in all directions except extension (flexion 141 degrees, extension 36 degrees, pronation 77 degrees, and supination 61 degrees). There was one ulnar nerve palsy that only partially resolved. Another patient's elbow had initially subluxed due to excessive shortening of the humerus; however, he had an excellent ROM and was asymptomatic at 31 months. There were no dislocations or wound healing problems. Cast immobilization provides an effective means of promoting soft-tissue healing, permitting early discharge from the hospital and simplifying the postoperative rehabilitation while achieving satisfactory ROM without formal physical therapy.
View details for Web of Science ID A1989AJ74100018
View details for PubMedID 2752611
The clinical and roentgenologic data from 31 excised components from 19 revision arthroplasty cases were correlated with the histology and biochemistry of the membrane at the bone-cement or bone-prosthesis interface. Twenty-seven components were cemented and four were uncemented. Twenty-four implants were clinically and roentgenologically loose, one was possibly loose, and six were well fixed. Loose components, whether cemented or not, demonstrated statistically higher prostaglandin E2 levels in the surrounding membrane compared to the nonloose group. Collagenase and M-collagenase levels were absent or insignificantly low in all specimens; no detectable interleukin 1 beta was found. This suggests that prostaglandin E2 may be associated with the bone lysis associated with prosthesis loosening.
View details for Web of Science ID A1989AG08900017
View details for PubMedID 2545398
The purpose of this study was to investigate whether the salvage in the recovery room of blood from the drainage tubes of patients who had total joint arthroplasty was both feasible and efficacious. The cases of seventy-four patients who had seventy-six consecutive total hip or knee arthroplasties were studied prospectively. Intraoperative salvage of blood was performed using the Cell Saver. After closure of the fascial layer or joint capsule, the drainage tubes were connected to the Cell Saver in the operating room and remained connected in the recovery room for a mean of 2.9 hours. Blood that was collected in the recovery room was then processed and transfused back to the patient. The average amount of blood that was salvaged after different types of arthroplasty varied. The addition of bone cement to the acetabular side during primary total hip replacement decreased the amount of postoperative bleeding and of salvaged blood (p = 0.018), whereas cementing the femoral component had no statistically significant effect. Revision total hip replacement also resulted in more bleeding and in the collection of more blood in the recovery room than did primary total hip replacement (p = 0.03), especially if cement was not used (p less than 0.001). There were no statistical differences in the amount of blood that was collected in the recovery room after unilateral, bilateral, primary, or revision total knee replacement.(ABSTRACT TRUNCATED AT 250 WORDS)
View details for PubMedID 2745477
This study investigates risk factors associated with mechanical loosening of cemented total hip arthroplasties. Mechanical failure was evaluated using survivorship analysis on all arthroplasties performed at the authors' institution by the Orthopedic Service from March 1971 until September 1983. Failure was defined as the necessity for replacement of one or more components for any reason other than infection. The failure rate was approximately 1.7% per year and, at 12 years, 20% of the hips had failed. Variables evaluated as potential risk factors for arthroplasty revision included weight, gender, age, surgeon, preoperative functional status, prosthetic type, and diagnosis. A Cox proportional hazard analysis indicated that weight (p less than 0.015) and age (p = 0.087) are important determinants of hip failure. The use of regression trees identified subsets of patients at differing risks for failure. Patients who weighed less than 75.22 kg had the best outcome with a 90% survival to 12 years. Patients weighing more than 75.22 kg are at varying risk depending on their age. These data define a subset of special-risk patients not previously described. Patients weighing more than 75.22 kg who were older than 75.4 years had a revision rate of 73% by eight years.
View details for Web of Science ID A1989T494800022
View details for PubMedID 2917432
The purpose of this study was to compare the effects of human recombinant interleukin 1, alpha and beta, on articular cartilage. The effects of rIL-1 alpha and rIL-1 beta on proteoglycan degradation and synthesis following treatment of bovine articular cartilage in serum-free organ culture were quantified. Purified human IL-1 and both rIL-1 alpha and rIL-1 beta induced a two-fold or greater increase in glycosaminoglycan (GAG) release from cultured articular cartilage. Levels or rIL-1 alpha as low as 15 pM induced increased proteoglycan degradation whereas identical levels of rIL-1 beta did not. Killing of the cartilage cells abolished induced GAG release by all forms of IL-1. Analysis of proteoglycan size following IL-1 treatment showed limited degradation of material released into the culture medium or remaining within cartilage. Both forms of recombinant IL-1 inhibited GAG synthesis when continually present in the culture medium. Actinomycin D and cycloheximide inhibited IL-1 dependent cartilage destruction whereas indomethacin did not.
View details for Web of Science ID A1989T696500007
View details for PubMedID 2787228
Five pelvises were photographed, roentgenographed, and sequentially sectioned or reamed to determine the location and appearance of the acetabular teardrop figure. The teardrop is located inferomedially in the acetabulum, just superior to the obturator foramen. The lateral lip is the exterior, and the medial lip is the interior of the acetabular wall. The ilioischial line projects over the medial acetabulum only fortuitously on the straight anteroposterior (AP) roentgenogram. Because of parallax, the relationship between the ilioischial line and the teardrop changes for views varying as little as 10 degrees in horizontal obliquity from the true AP roentgenogram. Because the teardrop comprises a well-defined, constant portion of the medial acetabular wall whereas the ilioischial line does not, the authors recommend using the acetabular teardrop rather than the ilioischial line for the detection and measurement of medial and superior acetabular migration.
View details for Web of Science ID A1988R039800026
View details for PubMedID 3180571
The purpose of this study was to develop sensitive and accurate methods of quantitating bacterial glycocalyx. Coagulase-negative staphylococci were cultured in trypticase soy broth. Quantitation of slime production was evaluated using various methods of fixation and staining. The amount of dye associated with bacterial slime was assessed spectrophotometrically following solubilization of the dye-biofilm complex by 0.2 M NaOH at 85 degrees C for 1 h. Carnoy's solution was optimal for fixation of the slime, and toluidine blue staining was most reproducible. Fifteen strains of Staphylococcus epidermidis showed a gradation in biofilm production ranging from high, medium, to low that was strain stable. Irrespective of the technique used, high, medium, and low producers of bacterial slime remained in the same category and always showed significantly different optical density readings (p less than 0.05). In our experiments, solubilization of a toluidine blue-bacterial biofilm complex was a direct, simple, and efficient method for reproducibily quantitating glycocalyx. This method provides a useful means of rapid quantitation of biofilm production to assess its role in the infection process and in the response to antibiotic therapy.
View details for Web of Science ID A1988P849300006
View details for PubMedID 3404323
Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation. After radiotherapy, there was a marked decrease in the number and function of peripheral blood helper/inducer (Leu-3+) T lymphocytes, in the spontaneous secretion of interleukin-1 by synovial biopsy specimens, and in the activity of the joint disease. In contrast, levels of IgM, IgA, and IgG rheumatoid factors and C3 concentrations in blood and synovial fluid samples did not change significantly after therapy with total lymphoid irradiation.
View details for Web of Science ID A1988M309400004
View details for PubMedID 3257873
Twenty-one infected total hip arthroplasties in 19 patients performed between 1971 and 1982 were prospectively followed, using a computerized standard orthopaedic arthritis record. These cases represent an inclusive and unselected, consecutive series. The mean follow-up period from time of infection was 4.8 years (range, 1.2-11.7 years). Infection was diagnosed by positive bacteriologic culture. Ten hips grew a staphylococcal species, 5 a single gram-negative organism, 1 a Streptococcus, and 5 multiple organisms. At final follow-up evaluation, only three hips (14%) had the previously infected prosthesis still in situ, and these had no evidence of ongoing deep infection. Five additional hips (24%) were successfully salvaged after one- or two-stage prosthetic exchange. Two hips (10%) have an infected prosthesis in situ. Eleven hips (52%) had resection arthroplasty, three after attempts at prosthetic reinsertion. Therefore, at final follow-up evaluation, only 8 of the 21 hips (38%) have an apparently infection-free salvaged or reinserted prosthesis in place. Good prognostic factors for prosthetic salvage/successful reinsertion include Staphylococcus epidermidis infection and a traumatic etiology necessitating later hip arthroplasty. Poor prognostic factors include infection with Staphylococcus aureus or multiple organisms and a preoperative diagnosis of avascular necrosis.
View details for PubMedID 3397752
We calculated subchondral deformations and stresses in the femoral head and acetabulum during weight bearing using finite element models. Areas of high joint contact pressures on the femoral head were shown to correspond to high hydrostatic compression in subchondral bone. The magnitude of the subchondral bone compressive hydrostatic stress correlated with cartilage thickness and was highest in the superior femoral head and moderate at the acetabular roof. The seldom contacting surfaces of the medial-inferior and peripheral areas of the femoral head and the roof of the acetabulum had lower hydrostatic compression and significant subchondral bone tensile strains tangential to the joint surface. Initial cartilage fibrillation and osteophyte formation are often found in these areas. These findings suggest that fluctuating hydrostatic pressure inhibits vascular invasion and the degeneration and ossification of articular cartilage. The generation of tensile strain may promote the degenerative process by direct mechanical mechanisms. Additionally, since tensile strains are associated with a reduction in the compressive hydrostatic stresses in the cartilage and an increase in shear stresses, their presence may permit or promote vascular invasion, cartilage degeneration, and osteophyte formation. These mechanical principles in arthrosis are the same as those that have been previously demonstrated to guide the degeneration and ossification of the cartilage primordium during skeletal morphogenesis. In this sense, arthrosis may be viewed as the final stage in the degeneration and ossification of the cartilage anlage.
View details for Web of Science ID A1987M477800002
View details for PubMedID 3442205
In joints with bacterial arthritis, continuing prolonged destruction of cartilage may occur in spite of prompt, effective antibiotic therapy. We measured the extent to which early antibiotic therapy with ceforanide altered the degradation of the cartilage after arthritis due to Staphylococcus aureus had been produced in the knee joint in rabbits. Degradation of the cartilage was quantified by analyses for glycosaminoglycan and collagen. Three weeks after the infection was produced, the cartilage had lost more than half of its glycosaminoglycan whether the antibiotic therapy had been started at one, two, or seven days after infection. Beginning the antibiotic treatment one day after infection reduced over-all loss of collagen by 37 per cent and decreased the area of erosion of the infected articular surfaces. When antibiotic treatment was begun at four, eight, or twelve hours after infection, the loss of glycosaminoglycan averaged 18 per cent. Prophylaxis with antibiotics completely prevented any degradation of the cartilage. Clinical relevance: The findings reported here show how rapidly cartilage loses glycosaminoglycan when it is involved by arthritis caused by staphylococci and how early treatment of the infection reduces the loss of collagen. There is less protection against loss of glycosaminoglycan. The results emphasize the need for early diagnosis and treatment of infectious synovitis and support the rationale for early administration of antibiotics without waiting for identification of the responsible bacteria.
View details for PubMedID 3654698
View details for PubMedID 3454937
Human knee specimens were subjected to anterior-posterior, medial-lateral, varus-valgus, and torsional displacement tests. Loads were recorded for the intact joint and for the joint with all soft tissues cut except for the cruciate ligaments. The effect of condylar interference was determined for anterior-posterior, medial-lateral, and torsional displacements. The variation in load with flexion angle was considerable for medial-lateral (0-90-deg flexion) displacements, and less for varus-valgus (0-45-deg flexion) displacements. The cruciates were found to carry almost the entire anterior-posterior load; they carried a significant percentage of the medial-lateral load which varied considerably with flexion angle. A small, but not insignificant percentage of the varus-valgus load was carried by the cruciates and the variations with flexion angle were small. In torsion, the cruciates resisted only internal rotation. In the tested displacement ranges, condylar interference had a small effect on the medial-lateral load but did not affect anterior-posterior or torsional loads.
View details for Web of Science ID A1980KT68900001
View details for PubMedID 6965189
Cefoxitin was administered to 47 patients on an orthopedic service; 1 or 2 g of the drug was given intravenously every 4-8 hr. Thirty-one evaluated patients with acute or chronic infections of bone, joint, or muscle and tendon had an overall rate of cure of 84%. Ten patients with spinal cord injuries who had urinary tract infections due to Serratia or indole-positive Proteus were treated, and all 10 were cured. Significant adverse effects of cefoxitin included one case of fever due to the drug and three cases of superinfection. Cefoxitin therapy was successful in a variety of difficult-to-treat infections, including some of polymicrobial etiology.
View details for Web of Science ID A1979GR69900028
View details for PubMedID 318224
The outcome of total joint arthroplasty is determined by biological events at the bone-implant interface. Macrophages phagocytose implant or wear debris at the interface and release proinflammatory mediators such as interleukins 1 and 6, tumor necrosis factor-alpha, and prostaglandin E2. These mediators are thought to contribute to the resorption of periprosthetic bone. Previous studies of tissues harvested from the bone-implant interface of failed orthopaedic implants demonstrated a possible role for two other cytokines, granulocyte-macrophage colony-stimulating factor and interleukin-4. The present study examined the effects of in vitro challenge with polymethylmethacrylate particles on the expression of granulocyte-macrophage colony-stimulating factor by primary human monocytes/macrophages and the role of interleukin-4 in regulating this expression. The polymethylmethacrylate particles caused a dose-dependent release of granulocyte-macrophage colony-stimulating factor at 48 hours. This release was accompanied by increased expression of interleukins 6 and 1beta and tumor necrosis factor-alpha. Release of the lysosomal enzyme hexosaminidase also increased in response to the particles. Interleukin-4 inhibited the expression of granulocyte-macrophage colony-stimulating factor, interleukin-6, and tumor necrosis factor-alpha at 48 hours in a dose-dependent manner. The data presented in this study confirm the hypothesis that interleukin-4 downregulates particle-induced activation of macrophages, as demonstrated by the decreased release of proinflammatory mediators.
View details for Web of Science ID 000084603300001
View details for PubMedID 10632444
Expression of matrix metalloproteinase-9 mRNA in osteoarthritic and normal cartilage was analyzed using reverse transcription-polymerase chain reaction and in situ hybridization. Fifty-four osteoarthritic cartilage samples were obtained from 24 patients undergoing total knee arthroplasty. Sixteen normal cartilage samples were obtained from non-osteoarthritic knees of four autopsy cases. With normal cartilage, reverse transcription-polymerase chain reaction analysis for matrix metalloproteinase-9 mRNA showed that chondrocytes exhibited only a trace signal. In analysis of osteoarthritic cartilage, chondrocytes of moderately and severely fibrillated cartilage exhibited a 73-fold and 110-fold increase in matrix metalloproteinase-9 mRNA signal, respectively, relative to normal cartilage. Chondrocytes of nonfibrillated osteoarthritic cartilage exhibited a 6-fold increase (p < 0.02) in matrix metalloproteinase-9 mRNA signal relative to normal cartilage. Analysis of matrix metalloproteinase-9 mRNA expression in fresh-frozen sections of normal and osteoarthritic cartilage by in situ hybridization confirmed these results. This study showed that reverse transcription-polymerase chain reaction provides a sensitive index of mRNA levels in normal and osteoarthritic cartilage samples and suggests that increased expression of matrix metalloproteinase-9 precedes fibrillation of cartilage in the development of osteoarthritis.
View details for Web of Science ID A1997WL95000013
View details for PubMedID 9066532
Mechanical loading alters the metabolism of articular cartilage, possibly due to effects of shear stress on chondrocytes. In cultured chondrocytes, glycosaminoglycan synthesis increases in response to fluid-induced shear. This study tested the hypothesis that shear stress increases nitric oxide production in chondrocytes, and nitric oxide then influences glycosaminoglycan metabolism. Inhibitors of nitric oxide synthase, G proteins, phospholipase C, potassium channels, and calcium channels were also analyzed for effects on nitric oxide release and glycosaminoglycan synthesis. Fluid-induced shear was applied to primary high-density monolayer cultures of adult bovine articular chondrocytes using a cone viscometer. Nitric oxide release in chondrocytes increased in response to the duration and the magnitude of the fluid-induced shear. Shear-induced nitric oxide production was reduced in the presence of nitric oxide synthase inhibitors-but was unaffected by pertussis toxin, neomycin, tetraethyl ammonium chloride, or verapamil. The increase in glycosaminoglycan synthesis in response to shear stress was blocked by nitric oxide synthase inhibitors, pertussis toxin, and neomycin but not by tetraethyl ammonium chloride or verapamil. The phospholipase C inhibitor, neomycin, also decreased glycosaminoglycan synthesis in the absence of flow-induced shear. As studied here, shear stress increased nitric oxide production by chondrocytes, and the shear-induced change in matrix macromolecule metabolism was influenced by nitric oxide synthesis, G protein activation, and phospholipase C activation.
View details for Web of Science ID A1997WL95000012
View details for PubMedID 9066531
The roles of physical activity (both work and leisure time), obesity, and history of significant knee injury on the development of severe osteoarthrosis (OA) of the knee were evaluated. A case-control design compared 46 cases with a history of severe OA of the knee with 46 community controls matched for age and gender. Data were gathered with a self-administered questionnaire. The OA cases were 3.5 times more likely than controls to have been obese at 20 years of age, two to three times more likely than controls to have performed heavy work, and almost five times more likely than controls to have had a significant knee injury. In contrast, leisure-time physical activity was not significantly different in cases compared with controls. Obesity, significant knee injury, and long-term heavy physical activity are important risk factors for the development of OA of the knee.
View details for Web of Science ID A1990EL72000028
View details for PubMedID 2245553