Biomedical subjects

D J Schurman

Publications and source records attributed to D J Schurman.

At least 19 recordsLinked to original sources

PubMed2001

In vitro reaction to orthopaedic biomaterials by macrophages and lymphocytes isolated from patients undergoing revision surgery.

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.

Biocompatible Materials↗

PubMed2001

Interleukin-10 inhibits polymethylmethacrylate particle induced interleukin-6 and tumor necrosis factor-alpha release by human monocyte/macrophages in vitro.

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.

Biocompatible Materials↗

PubMed2001

Measurement of perioperative flexion-extension mechanics of the knee joint.

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.

Arthroplasty, Replacement, Knee↗

PubMed2000

G-protein activity requirement for polymethylmethacrylate and titanium particle-induced fibroblast interleukin-6 and monocyte chemoattractant protein-1 release in vitro.

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.

Biocompatible Materials↗

PubMed2000

Monocyte migration inhibitory factor synthesis and gene expression in particle-activated macrophages.

This study analysed MIF mRNA and protein expression in human macrophages exposed in vitro to polymethylmethacryate and titanium alloy particles. MIF levels released from macrophages without exposure to particles were in the range of 2-4 ng/ml. Exposure of macrophages to particles as demonstrated increased MIF release at 0. 075%-0.225% v/v particle concentration, which was maximal at 12-24 h. MIF mRNA signal levels in cells with and without particles at a concentration of 0.075% showed no significant differences in a time course experiment. The profile of MIF release in response to increasing particle concentration coincided with increased release of lactate dehydrogenase. The viability of the cells was unchanged by the addition of particles as determined by 3H-thymidine uptake. These data suggest that MIF expression may represent an independent macrophage response to locally high particle concentrations.

Alloys↗

PubMed2000

Induction of interleukin-6 release in human osteoblast-like cells exposed to titanium particles in vitro.

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.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2000

Effects of shear stress on articular chondrocyte metabolism.

The articular cartilage of diarthrodial joints experiences a variety of stresses, strains and pressures that result from normal activities of daily living. In normal cartilage, the extracellular matrix exists as a highly organized composite of specialized macromolecules that distributes loads at the bony ends. The chondrocyte response to mechanical loading is recognized as an integral component in the maintenance of articular cartilage matrix homeostasis. With inappropriate mechanical loading of the joint, as occurs with traumatic injury, ligament instability, bony malalignment or excessive weight bearing, the cartilage exhibits manifestations characteristic of osteoarthritis. Breakdown of cartilage in osteoarthritis involves degradation of the extracellular matrix macromolecules and decreased expression of chondrocyte proteins necessary for normal joint function. Osteoarthritic cartilage often exhibits increased amounts of type I collagen and synthesis of proteoglycans characteristic of immature cartilage. The shift in cartilage phenotype in response to altered load yields a matrix that fails to support normal joint function. Mathematical modeling and experimental studies in animal models confirm an association between altered loading of diarthrotic joints and arthritic changes. Both types of studies implicate shear forces as a critical component in the destructive profile. The severity of cartilage destruction in response to altered loads appears linked to expression of biological factors influencing matrix integrity and cellular metabolism. Determining how shear stress alters chondrocyte metabolism is fundamental to understanding how to limit matrix destruction and stimulate cartilage repair and regeneration. At present, the precise biochemical and molecular mechanisms by which shear forces alter chondrocyte metabolism from a normal to a degenerative phenotype remain unclear. The results presented here address the hypothesis that articular chondrocyte metabolism is modulated by direct effects of shear forces that act on the cell through mechanotransduction processes. The purpose of this work is to develop critical knowledge regarding the basic mechanisms by which mechanical loading modulates cartilage metabolism in health and disease. This presentation will describe the effects of using fluid induced shear stress as a model system for stimulation of articular chondrocytes in vitro. The fluid induced shear stress was applied using a cone viscometer system to stimulate all the cells uniformly under conditions of minimal turbulence. The experiments were carried using high-density primary monolayer cultures of normal and osteoarthritic human and normal bovine articular chondrocytes. The analysis of the cellular response included quantification of cytokine release, matrix metalloproteinase expression and activation of intracellular signaling pathways. The data presented here show that articular chondrocytes exhibit a dose- and time-dependent response to shear stress that results in the release of soluble mediators and extracellular matrix macromolecules. The data suggest that the chondrocyte response to mechanical stimulation contributes to the maintenance of articular cartilage homeostasis in vivo.

Adult↗

PubMed1999

Chemotaxis and activation of particle-challenged human monocytes in response to monocyte migration inhibitory factor and C-C chemokines.

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.

Biocompatible Materials↗

PubMed1999

Interferon-gamma exacerbates polymethylmethacrylate particle-induced interleukin-6 release by human monocyte/macrophages in vitro.

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.

Awards and Prizes↗

PubMed1999

Interleukin-4 inhibits granulocyte-macrophage colony-stimulating factor, interleukin-6, and tumor necrosis factor-alpha expression by human monocytes in response to polymethylmethacrylate particle challenge in vitro.

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.

Dose-Response Relationship, Drug↗

PubMed1999

Induction of macrophage C-C chemokine expression by titanium alloy and bone cement particles.

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.

Antibodies, Monoclonal↗

PubMed1999

Signaling pathways for tumor necrosis factor-alpha and interleukin-6 expression in human macrophages exposed to titanium-alloy particulate debris in vitro.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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

Alloys↗

PubMed1998

Complex primary and revision total knee arthroplasty using the condylar constrained prosthesis: an average 5-year follow-up.

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.

Adult↗

PubMed1998

Joint infection.

Explore the source record for details and available documents.

Arthritis, Infectious↗

PubMed1998

Prediction of postoperative knee flexion in Insall-Burstein II total knee arthroplasty.

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.

Aged↗

PubMed1998

Induction of matrix metalloproteinase expression in human macrophages by orthopaedic particulate debris in vitro.

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.

Alloys↗

PubMed1997

Nitric oxide and G proteins mediate the response of bovine articular chondrocytes to fluid-induced shear.

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.

Animals↗

PubMed1997

Osteoarthritis: differential expression of matrix metalloproteinase-9 mRNA in nonfibrillated and fibrillated cartilage.

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.

Aged↗