Biomedical subjects

John Antoniou

Publications and source records attributed to John Antoniou.

36 records · Page 2Linked to original sources

PubMed2004

Value and limitations of using the bovine tail as a model for the human lumbar spine.

STUDY DESIGN: The contents of DNA, proteoglycan, type II collagen, and denatured type II collagen in the bovine coccygeal intervertebral discs were examined in situ in relation to disc level, age, and tissue region. OBJECTIVE: To determine whether bovine coccygeal discs are a suitable model to study human lumbar discs. SUMMARY OF BACKGROUND DATA: Bovine coccygeal discs have been suggested as a suitable alternative model because they are readily available, in contrast to human discs, and represent a common source of tissue in the disc field. However, it is not known whether the changes in matrix contents in bovine coccygeal discs are similar to those found in the human lumbar spine. METHODS: Intervertebral discs from bovine tails were dissected into the nucleus pulposus (NP) and anulus fibrosus (AF). Tissues were weighed and analyzed for matrix contents using specific assays. RESULTS: Similar to water content, the proteoglycan content was higher in the NP than in the AF. Water content of the bovine NP did not change with age, unlike the proteoglycan content, which decreased. type II collagen content was higher in the NP than in the AF, and both did not change overall significantly with age. The percent of denatured type II collagen decreased with age only in the NP. The DNA content did not vary with age in the AF and in the NP. CONCLUSION: Differences in matrix contents exist between the bovine coccygeal discs and the human lumbar spine. Thus, caution must be exercised when using the bovine tail as a model for the human lumbar spine in biochemical studies.

Aging↗

PubMed2004

Production of prostaglandin D(2) by human osteoblasts and modulation of osteoprotegerin, RANKL, and cellular migration by DP and CRTH2 receptors.

UNLABELLED: Human osteoblasts produce PGD(2), which acts on the DP receptor to decrease osteoprotegerin production and on the CRTH2 receptor to decrease RANKL expression and to induce osteoblast chemotaxis. These results indicate that activation of CRTH2 may lead to an anabolic response in bone. INTRODUCTION: Whereas the actions of prostaglandin (PG)E(2) as a modulator of bone and osteoblast function are relatively well characterized, little is known about PGD(2) and bone metabolism. The objectives of this study were to determine if human osteoblasts can produce PGD(2), which prostaglandin D(2) synthases are implicated in this synthesis, to identify the PGD(2) receptors (DP and CRTH2) on these cells and to characterize the biological effects resulting from their activation. MATERIALS AND METHODS: RT-PCR analysis and immunohistochemistry were used to detect PGD(2) receptor and synthases in cultured human osteoblasts. Immunohistochemistry was used to identify the synthases and receptors in human bone tissue. Intracellular cAMP and calcium levels were determined to verify receptor activation. The cells were stimulated with PGD(2) or the specific agonists BW 245C (DP) and DK-PGD(2) (CRTH2), and the resulting effects on osteoprotegerin (OPG) secretion, RANKL expression, and chemotaxis were determined. Osteoblast production of PGD(2) was evaluated by measuring PGD(2) in the culture supernatants after stimulation with interleukin (IL)-1, TNF-alpha, PTH, vascular endothelial growth factor (VEGF), and insulin-like growth factor I (IGF-I). RESULTS: Human osteoblasts in culture generated PGD(2) when stimulated. Both osteoblasts in culture and in situ present the lipocalin-type PGD(2) synthase only. Both DP and CRTH2 receptors were present in human osteoblasts in culture and in situ. Stimulation of DP resulted in an increase in cAMP, whereas CRTH2 increased the intracellular calcium level. OPG production was reduced by 60% after DP receptor stimulation, whereas CRTH2 receptor stimulation decreased RANKL expression on human osteoblasts. As reported for other cell types, CRTH2 was a potent inducer of chemotaxis for human osteoblasts in culture. CONCLUSIONS: Human osteoblasts in culture produce PGD(2) under biologically relevant stimuli through the lipocalin-type PGD(2) synthase (L-PGDS) pathway. As an autacoid, PGD(2) can act on DP and CRTH2 receptors, both present on these cells. Specific activation of CRTH2 could lead directly and indirectly to an anabolic response in bone.

Bone and Bones↗

PubMed2004

Induction of apoptosis and necrosis by metal ions in vitro.

There has been a renewed interest in the use of the metal-on-metal (MOM) implants for total hip arthroplasty (THA). It is well known, however, that the MOM articulation generates both metal particles and ions. The physiologic effects of these ions are poorly understood and their potential toxicity remains a cause for concern. In the present study, murine J774 macrophages were incubated with Co2+ and Cr3+ ions and the mode of cell death (apoptosis/necrosis) was evaluated in vitro by transmission electron microscopy and cell death ELISA. Overall, results demonstrated that the mode of cell death was dependent on the ion concentration and the incubation time. Indeed, at short incubation times (24 h), the noninflammatory process of apoptosis was predominant. At longer incubation times (48 h), however, necrosis was predominant at higher ion concentrations.

Animals↗

PubMed2004

Effect of cobalt and chromium ions on bcl-2, bax, caspase-3, and caspase-8 expression in human U937 macrophages.

The bcl-2 and caspase families of proteins play a central role in the modulation of apoptosis. The purpose of this study was to analyze the effect of Co(2+) and Cr(3+) ions on the expression of bcl-2, bax, caspase-3 and caspase-8 to better understand the mechanisms leading to ion-induced apoptosis in macrophages. U937 human macrophages were exposed to Co(2+) and Cr(3+) ions. The expression of proteins was measured by Western blot while caspase activities were measured by colorimetric assay. Results show that Co(2+) ions inhibited bcl-2 expression with significant effect (p<0.05) after 16 h and a maximal 52% inhibitory effect after 24 h. Co(2+) stimulated bax expression with a significant stimulation (p<0.05) after 8 h and a maximal 1.75-fold increase after 16 h. Co(2+) also stimulated the expression of the active fragment of caspase-3 as well as caspase-3 activity maximal increase after 24 h. Co(2+) ions had no effect on caspase-8 expression or activity.Cr(3+) ions inhibited bcl-2 expression with significant effect (p<0.05) after 16 h and a maximal 43% inhibitory effect after 24 h. Cr(3+) stimulated bax expression with significant stimulation (p<0.01) after 8h and a maximal 2.25-fold increase after 24 h. Cr(3+) ions also stimulated the expression of the active fragments of caspase-3 and -8, as well as the activities of both proteases. The effect of Cr(3+) ions on the expression of both caspase active fragments was maximal after 16 h incubation. In conclusion, our results suggest that the modulation of the expression of proteins from the bcl-2 and the caspase families of proteins are implicated in the induction of macrophage apoptosis by Co(2+) and Cr(3+) ions.

Apoptosis↗

PubMed2004

Apparent diffusion coefficient of intervertebral discs related to matrix composition and integrity.

While tremendous work has been performed to characterize degenerative disc disease through gross morphologic, biochemical, and histologic grading schemes, the development of an accurate and noninvasive diagnostic tool is required to objectively detect changes in the matrix with aging and disc degeneration. In the present study, quantitative magnetic resonance was used to determine if the quality of the nutritional supply to the intervertebral disc at various ages and levels of degeneration could be assessed through measurement of the apparent diffusion coefficients (ADCs). Modifications of the nucleus pulposus matrix content, specifically of water and glycosaminoglycan contents, with age and disc degeneration, were reflected in correlating changes in the ADCs. From unforced stepwise linear regression analyses, relations were established showing that decreases in glycosaminoglycan or water contents in the nucleus pulposus resulted in direct decreases in the ADCs. Relations obtained for the ADCs of the nucleus pulposus were direction dependent, in conformity with the anisotropic diffusion in the intervertebral discs. Changes in matrix integrity, as evidenced by the percentage of denatured collagen, were also detected in the nucleus pulposus with a low positive correlation to the ADC along the height of the disc and an inverse statistically significant regression to the ADC along the anterior to posterior axis of the disc. Correlations between the matrix content and integrity of the annulus fibrosus and its ADCs were not as evident, with only the ADC in the lateral direction of the disc of the anterior annulus fibrosus able to reflect changes in matrix content. The information obtained by the ADCs, particularly of the nucleus pulposus, can potentially be used in combination with quantitative T1, T2, and MT parameters to noninvasively obtain a quantitative assessment of the disc matrix composition and structural integrity.

Adolescent↗

PubMed2004

In-hospital cost of total hip arthroplasty in Canada and the United States.

BACKGROUND: There is little information comparing the costs of specific surgical procedures performed in Canada and those done in the United States. The objective of this study was to compare the in-hospital costs associated with primary total hip arthroplasty performed in the two countries. METHODS: In-hospital costs of 1679 consecutive patients (940 Canadian and 739 American patients) who underwent total hip arthroplasty were extracted from three Canadian and three United States teaching hospitals between 1997 and 2001. Participating hospitals used the same cost accounting system to provide per-patient demographic, clinical, and cost data. Canadian dollar costs were converted to United States dollar costs with use of purchasing power parities. RESULTS: The baseline clinical characteristics of patients undergoing total hip arthroplasty in Canada and the United States were similar. The American patients were a mean of 4.6 years older than the Canadian patients (mean [and standard deviation], 67.8 +/- 12.4 years compared with 63.2 +/- 14.9 years). The median cost for the primary arthroplasty was $6080 (mean [and standard error of the mean], $6766 +/-$119) at the three Canadian hospitals and $12,846 (mean, $13,339 +/-$131) at the United States hospitals (p < 0.0001). The mean length of stay (and standard deviation) was 7.2 +/- 4.7 days for the Canadian patients and 4.2 +/- 2.0 days for the American patients. Implants at one hospital in the United States were found to be four times more costly than those in a Canadian hospital. CONCLUSIONS: Higher in-hospital costs were found for the American hospitals despite the fact that they had a significantly shorter patient length of stay compared with Canadian centers (p < 0.0001). Canadian hospitals should follow the lead of their counterparts in the United States and implement strategies to decrease the length of stay in the hospital, while institutions in the United States should revisit their ability to better manage the costs related to a primary total hip arthroplasty, particularly by controlling unit costs.

Aged↗

PubMed2003

A synthetic peptide of link protein stimulates the biosynthesis of collagens II, IX and proteoglycan by cells of the intervertebral disc.

To date, there have been no reports on the effect on disc cells of the intervertebral disc (IVD) of the amino terminal peptide of link protein (DHLSDNYTLDHDRAIH) (link N) which is generated by the cleavage of human link protein by stromelysins 1 and 2, gelatinase A and B, and collagenase between His(16) and Ile(17). However, link N has been shown to act as a growth factor and stimulate synthesis of proteoglycans and collagen by chondrocytes of human articular cartilage. There are also no studies on the effect of link N on type IX collagen in any tissue. In the studies reported here, a serum-free pellet culture system has been used to examine whether link N can play a role in maintaining the integrity of disc matrix, specifically at the level of matrix assembly by cells of the IVD. Using this culture system, we determined the capacity of link N to stimulate accumulation of these matrix proteins in the annulus fibrosus (AF) and nucleus pulposus (NP). Gross inspection of separate AF and NP pellet cultures in the absence of link N revealed a progressive increase in size and a transition from "spherical" to "polygonal" pellets after centrifugation. Addition of 10 ng/ml link N resulted in increased pellet sizes for both AF and NP pellet cultures. Link N increased proteoglycan, type II and type IX collagen contents with an increase in DNA content over time. This study demonstrates that link N can act directly on disc cells to stimulate matrix production, which involves increased accumulation of proteoglycan, and types II and IX collagens. This study also identifies the value of pellet cultures for studies of the IVD cells in a serum-free chemically defined medium, in which pellets can continue growing in size in response to growth factors with minimal cell loss. Link N may have value in stimulating the growth and regeneration of the damaged IVD.

Amino Acid Sequence↗

PubMed2003

TNF-alpha secretion and macrophage mortality induced by cobalt and chromium ions in vitro-qualitative analysis of apoptosis.

Metal ion toxicity is a major cause for concern in metal-metal hip replacements. A previous study in our laboratory demonstrated that Co(2+) and Cr(3+) induce macrophage apoptosis in vitro at 24h, with the implication of a caspase-3 pathway. The aim of the present study was to look at the effect of a prolonged incubation time on macrophage response with regards to TNF-alpha secretion and macrophage mortality, more specifically apoptosis. J774 macrophages were exposed for up to 48 h to 0-10 ppm Co(2+) and 0-500 ppm Cr(3+). ELISA results demonstrated that Co(2+ )and Cr(3+) induced a concentration- and time-dependent increase of TNF-alpha secretion, but a decrease at the highest concentrations of Cr(3+) (350-500 ppm). This decrease was most likely due to a high toxicity of Cr(3+) at such concentrations. Higher levels of TNF-alpha were observed with Co(2+) than Cr(3+), demonstrating a higher stimulatory effect of this ion. Trypan blue and flow cytometry results demonstrated that both Co(2+) and Cr(3+) ions induce macrophage mortality in a dose- and time-dependent manner. The number of cells decreased when ion concentrations increased, especially at 48 h. In parallel with the TNF-alpha results, Co(2+) was more toxic than Cr(3+) since the maximal effects were reached with lower concentrations (8-10 ppm vs. 350-500 ppm, respectively). DNA analysis demonstrated that both Co(2+) and Cr(3+) ions induce macrophage apoptosis, with a stronger signal at 24h than at 48 h, suggesting the presence of more necrosis after 48 h. PARP cleavage, another marker of apoptosis, was observed at both 24 and 48 h, with a maximum intensity at 48 h and with the highest concentrations of ions. In conclusion, this study demonstrates that both Co(2+) and Cr(3+) ions can induce the release of TNF-alpha and macrophage mortality in a dose- and time-dependent manner. More specifically, Co(2+) and Cr(3+) ions induced apoptosis after both 24 and 48 h incubation, although DNA analysis suggested the presence of necrosis at 48 h. The relative importance of apoptosis and necrosis in the induction of macrophage mortality by these metal ions remains to be investigated.

Animals↗

PubMed2003

Effect of pamidronate on the stimulation of macrophage TNF-alpha release by ultra-high-molecular-weight polyethylene particles: a role for apoptosis.

The demonstration that one of the mechanisms of action of bisphosphonates (BPs) is the induction of osteoclast and macrophage apoptosis, suggests a potent therapeutic role for the BPs and other apoptosis-modulating agents in the management of periprosthetic osteolysis. The purpose of this study was to improve our understanding of the basic underlying molecular events leading to the inhibitory effect of pamidronate on the macrophage response to ultra-high-molecular-weight polyethylene (UHMWPE) particles. Murine J774 macrophages were incubated for 0-72 h in the presence of UHMWPE particles and/or pamidronate. TNF-alpha release was measured by ELISA while poly(ADP-ribose)polymerase (PARP) expression was measured by Western blot. DNA was analyzed on agarose. The appearance of PARP fragment and the fragmentation of DNA were used as markers of apoptosis. We observed a dose-dependent response to UHMWPE particles with TNF-alpha release reaching 4, 10, and 19 times control with 10, 25, and 125 particles/macrophage, respectively. UHMWPE particles (25 particles/macrophage) stimulate TNF-alpha release by a factor of 10, 7, and 6 after 24, 48, and 72 h, respectively, indicating a rapid stimulating effect of UHMWPE particles on TNF-alpha release. Our results also showed that at 10 particles/macrophage, pamidronate inhibits UHMWPE-induced TNF-alpha release by 12%, 14%, and 23% respectively after 24, 48, and 72 h (p<0.05 vs. 24 and 48 h). With 25 particles/macrophage, the inhibition of TNF-alpha reached 9%, 12%, and 15% after 24, 48, and 72 h (p<0.05 vs. 24 h), respectively. There is no significant difference between the inhibition by pamidronate of TNF-alpha release induced by 125 particles/macrophages at 24, 48, and 72 h. When cells are pre-incubated for 48 h with pamidronate prior to addition of UHMWPE particles for 24 h, we observed an increased inhibition of TNF-alpha compared to the co-incubation protocol. The inhibiting effect of pamidronate reaches 56% when pre-incubated with macrophages prior to incubation with 10 particles of UHMWPE/macrophage (p<0.05 vs. co-incubation).Co-incubation of pamidronate with UHMWPE particles also led to the appearance of the proteolytic PARP fragment after 24 h incubation. We also demonstrated the stimulation of DNA fragmentation (DNA laddering) after 48-72 h with pamidronate. The proteolytic cleavage of PARP, an early event in the induction of apoptosis, precedes the inhibition of UHMWPE particle-induced TNF-alpha release by pamidronate whereas the fragmentation of DNA, a late apoptotic event, parallels this inhibition. Our results suggest the induction of macrophage apoptosis is associated with the inhibitory effect of pamidronate on TNF-alpha release. There is a need for the development of medical management of periprosthetic osteolysis. The demonstration that drugs such as pamidronate induce specific apoptosis-related pathways in macrophages contributes data for a rational approach in the treatment and/or prevention of periprosthetic osteolysis.

Animals↗

PubMed2003

Milwaukee shoulder: correlating possible etiologic variables.

The current study evaluated the relative correlation of apatite crystal-induced inflammation and rotator cuff deficiency in the development of cuff tear arthropathy. Thirty-seven patients with full thickness rotator cuff tears were evaluated by history, physical examination, and plain radiographs. Thirty patients had surgical intervention for their rotator cuff defects, and calipers were used intraoperatively to quantify the size of the tear in its largest diameter. The remaining seven patients were treated nonoperatively and the size of the tear was quantified using magnetic resonance imaging. Synovial fluid was obtained from all patients and analyzed for crystal content using an alizarin red stain. Synovial fluid also was analyzed for leukocyte count and differential, prostaglandin E, and matrix metalloproteinase. An unpaired Student's t test revealed that significantly higher levels of prostaglandin E were found in the synovial fluid of patients with apatite crystals, shown by alizarin red stain. Chi squared analysis showed that patients with elevated crystal levels were significantly more likely to have large rotator cuff tears or glenohumeral arthritis. Establishing such relations potentially can elucidate the etiology and treatment of this complex disorder.(2) (2)

Arthritis↗

PubMed2002

Sites of collagenase cleavage and denaturation of type II collagen in aging and osteoarthritic articular cartilage and their relationship to the distribution of matrix metalloproteinase 1 and matrix metalloproteinase 13.

OBJECTIVE: To determine the sites of cleavage and denaturation of type II collagen (CII) by collagenase(s) in healthy and osteoarthritic (OA) human articular cartilage and their relationship to the distribution of matrix metalloproteinase 1 (MMP-1) and MMP-13. METHODS: Single (per subject) full-depth specimens from femoral condylar cartilage were isolated from articulating surfaces at autopsy from 8 subjects without arthritis and during arthroplasty from 10 patients with OA. Fixed frozen sections of cartilage were examined by immunoperoxidase localization, using antibodies to the collagenase-generated cleavage site in CII, to an intrachain epitope recognized only in denatured CII, and to MMP-1 and MMP-13 (proenzyme, activated enzyme, or enzyme/inhibitor complex). RESULTS: Staining for collagen cleavage, denaturation, and both MMPs was weak to moderate and was frequently observed in pericellular sites in cartilage from younger, nonarthritic subjects. In specimens from older subjects, this staining was often more widespread and of greater intensity. Similar staining was usually, but not always, seen for all antibodies. In OA cartilage, staining was often stronger and more intense than that in normal cartilage from older subjects, and the distribution of staining was often similar for the different antibodies. Pericellular staining in the deep zone was frequently more pronounced in arthritic cartilage and extended to territorial and sometimes interterritorial sites. In very degenerate specimens, staining was distributed throughout most of the cartilage matrix. CONCLUSION: These observations provide evidence for the presence of limited cleavage and denaturation of CII restricted to mainly pericellular and superficial sites in cartilage from younger, healthy subjects, where MMP-1 and MMP-13 are also selectively localized. Collagen degradation is more extensive and often more pronounced in cartilage from older, nonarthritic subjects. Characteristic changes in early OA are similar to those seen with aging in cartilage from older, healthy subjects, with collagen damage and collagenases concentrated closer to the articular surface. There was usually a close correspondence between the cleavage and denaturation of CII and the sites at which these collagenases were detected, suggesting that both MMPs are involved in the physiology and pathology. There was no evidence that the damage to CII is ordinarily initiated in sites other than at and near the articular surface and around chondrocytes.

Adult↗

PubMed2002

Differential apoptotic response of J774 macrophages to alumina and ultra-high-molecular-weight polyethylene particles.

We recently identified apoptosis in in vitro wear particle-stimulated macrophages. The recent explosion of interest in apoptosis lies in the fact that it is under positive and negative regulation through evolutionary conserved biochemical pathways. It may also be possible to modulate macrophage apoptosis in the treatment of periprosthetic osteolysis. The purpose of this study was to compare the macrophage response to identically sized particles of alumina ceramic (Al2O3) and ultra-high-molecular-weight polyethylene (UHMWPE) in terms of TNF-alpha release and induction of apoptosis. J774 mouse macrophages were incubated for 0-24 h in the presence of Al2O3 and UHMWPE particles. TNF-alpha release was measured by ELISA; Poly(ADP-ribose)polymerase (PARP) and caspase-3 expression was analyzed by Western blot; DNA fragmentation (DNA laddering) was visualized on agarose gel containing ethidium bromide. Al2O3 particles induced TNF-alpha release after 4 h incubation with concentrations reaching 483 and 800 pg/ml after 24 h with 125 and 250 particles/macrophage, respectively (control = 161 pg/ml) (P < 0.05 vs. control). The same concentrations of UHMWPE particles induced a much larger and significant TNF-alpha release after only 1 h incubation, increasing up to 6250 pg/ml after 24 h (P < 0.05 vs. control). Western blot analysis demonstrated that the active caspase-3 fragment (17 kDa) and the proteolytic PARP fragment (85 kDa) were expressed after 2 h incubation with 125 and 250 Al2O3 particles/macrophage. The active caspase-3 and the PARP fragment had lower expression and appeared after a longer incubation time (8 h) with 125 and 250 UHMWPE particles/macrophage. Finally, DNA fragmentation (DNA laddering) was observed after 16 h with 125 and 250 particles of Al2O3 per macrophage whereas no laddering was induced by UHMWPE particles even after 24 h incubation. This study shows that although both Al2O3 and UHMWPE particles induce TNF-alpha release, this stimulation was much greater (8-10 times higher) with UHMWPE than Al2O3 (P < 0.05 vs. control). As well, the induction of apoptosis, as measured by activation of caspase-3, PARP cleavage and DNA laddering, is different for these two particles, being faster and more important with Al2O3 than UHMWPE. We hypothesize that the ability of Al2O3 to induce macrophage apoptosis may explain the lower TNF-alpha release observed with these particles and explain the differences seen in osteolysis patterns of ceramic-ceramic (CC) vs. metal-polyethylene (Mpe) articulations. In conclusion, apoptosis may be a major internal mechanism to decrease macrophage activity and may be a desired therapeutic endpoint. The identification of an apoptosis-related pathway in the macrophage response to ceramic particles provides crucial data for a rational approach in the treatment and/or prevention of periprosthetic osteolysis.

Aluminum Oxide↗

PubMed2002

Expression of caspase-8 and caspase-3 proteins in interface membranes from aseptically loose total hip arthroplasty.

The terminal events leading to periprosthetic osteolysis are multifactorial and modulation of this process after the stage of mediator release has been demonstrated futile. We demonstrated that ceramic induce macrophage apoptosis in vitro. More recently, we and others demonstrated the presence of apoptosis in interface membranes (IMs) from aseptically loose total hip arthroplasty (THA). The purpose of this study was to characterize the mechanisms leading to apoptosis in these pseudomembranes. Western blot analysis was used to characterize the expression of caspase-3, caspase-8, poly(ADP-ribose)polymerase (PARP), and p53 proteins in IM from 35 patients (40 specimens) with a mean age of 58 years (range, 28-88 years) at the time of revision. Tissue harvested at the time of routine hardware removal served as control. Our results show that caspase-3 and caspase-8 pro-enzymes were expressed in both control and IM tissues. Our results also showed that caspase-3 active fragment (17 kDa) as well as caspase-8 active fragment (18 kDa) were expressed in IMs but absent in control tissues. We also demonstrated that both the native PARP (113 kDa) and its proteolytic fragment (89 kDa) were present in osteolytic IMs. Control membranes expressed only the 113 kDa native form of PARP. The over-expression of caspase-3 caspase-8 active fragments and the presence of PARP fragment were observed on both the acetabular and femoral sides of the prostheses. Finally, our results showed the absence of p53 expression in both osteolytic IMs and control tissues. In conclusion, our results suggest that the caspase/PARP pathway plays an active role in the activity of IMs from aseptically loose THAs.

Journal Article↗

PubMed2000

Extensively Coated Cementless Femoral Components in Revision Hip Arthroplasty.

A septic loosening and osteolysis can compromise the available host bone in patients requiring revision hip arthroplasty. Secure fixation of revision femoral components may not be possible if reliant only on proximal femoral bone for biologic fixation or cement interdigitation. The challenge for the revision arthroplasty surgeon is to find the best method to secure the implant in a femur with deficient bone proximally that will provide stability for load bearing and motion. In addition to providing stability, the implant must be durable and maintain long-term fixation. With over 16 years of experience with fully porous coated femoral revision implants, we have found that maximizing prosthetic-bone fit in the proximal femoral diaphyseal bone provides reliable long-term fixation in the majority of femoral revision cases.

Journal Article↗

PubMed1998

Lumbar intradiscal pressure measured in the anterior and posterolateral annular regions during asymmetrical loading.

OBJECTIVE: To analyze the effect of asymmetrical loading on intradiscal pressure. DESIGN: Human cadaveric lumbar spines were instrumented with multiple pressure sensors and subjected to external mechanical loads. BACKGROUND: Tears and radial fissures in the posterolateral annulus with no evidence of annular protrusion or nuclear extrusion are frequently observed in non-degenerated intervertebral discs. Cadaveric studies have shown that asymmetrical loads lead to posterolateral herniation. Regional overload may be responsible for a progressive structural weakness of the posterolateral annular fibres. METHODS: Three needles each equipped with three independent pressure sensors were inserted in the midplane of the L(3)/L(4) intervertebral disc (n = 16) in the anterior, right posterolateral and left posterolateral regions. Axial rotation was applied in the upright, flexed and extended positions and the pressures recorded. RESULTS: The largest intradiscal pressure increase was observed in the posterolateral inner annular regions, more so in flexion than extension, when combined with axial rotation. Significant centripetal pressure gradients were found only in the posterolateral needles during the upright and flexed positions. CONCLUSIONS: When applying compression and axial rotation, the posterolateral inner annular zones of the intervertebral disc show high stress peaks and centripetal pressure gradients. Asymmetrical loads (rotation) combined with postural changes in the sagittal plane increase these effects, and may be responsible for a chronic mechanical overload of these regions. RELEVANCE: Our findings suggest a predilection for the posterolateral inner annular regions to mechanical failure, especially under asymmetrical loading.

Journal Article↗

PubMedDate not supplied

Iliotibial band reconstruction for treatment of glenohumeral instability associated with irreparable capsular deficiency.

The surgical management of patients with recurrent anterior instability after failed surgery can be complicated by the loss of capsular tissue and, in some cases, irreparable tears of the subscapularis tendon. We describe a new surgical technique for reconstruction of the capsular ligaments using the iliotibial band (ITB) to reconstruct deficient capsular tissues, and we report the results of 7 patients. All patients had prior surgery, with a mean of 2.2 procedures, and recurrent instability as the primary indication for their index and revision surgeries. After ITB reconstruction, the patients demonstrated significant improvement in their American Shoulder and Elbow Surgeons (ASES) score (P =.0004), and no patient had any persistent symptoms of instability. Physiologic range of motion and function were maintained. We would recommend our method of ITB reconstruction for patients with instability and capsular deficiency after failed surgery and believe that this procedure has advantages over those previously described. Capsular deficiency and persistent instability after prior surgery can occur after prior open or arthroscopic surgery. Capsular deficiency has been described after thermal capsulorrhaphy and is thought to represent excessive thermal injury and tissue necrosis. After open capsulorrhaphy, capsular deficiency can be associated with subscapularis tendon deficiency.(4,6-8,12,13) Capsular deficiency occurring after either open or arthroscopic surgery presents a difficult surgical challenge. The purpose of this case series is to evaluate our experience in the surgical management of recurrent glenohumeral instability after surgery initially performed for treatment of glenohumeral instability that failed and is associated with irreparable tears of the subscapularis and capsular deficiency. The primary objectives of this study are to describe the surgical technique for capsular reconstruction with ITB and to report the clinical results in 7 patients.

Adult↗

PubMedDate not supplied

Biological evaluation of chitosan salts cross-linked to genipin as a cell scaffold for disk tissue engineering.

Degenerative disc disease has been implicated as a major component of spine pathology. However, although biological repair of the degenerate disk would be the ideal treatment, there is no universally accepted scaffold for tissue engineering of the intervertebral disk. To help remedy this, we investigated the gelation kinetics of various concentrations (2.5 to 10%) of two water-soluble chitosan chlorides (low molecular weight Protasan UP CL113 and high molecular weight Protasan UP CL213) and two chitosan glutamates (low molecular weight Protasan UP G113 and high molecular weight Protasan UP G213). Various concentrations (5 to 20%) of genipin, a naturally occurring cross-linking reagent used in herbal medicine and in the fabrication of food dyes, were used to prepare cross-linked chitosan hydrogels. The results show that 2.5% Protasan UP G213 cross-linked to 5% genipin was the best candidate. This formulation gelled fastest at 37 degrees C, and maintained 95% viability of encapsulated cultured disk cells. The gel did not produce an inflammatory reaction when injected subcutaneously into C57BL/6 mice and is therefore biocompatible. Most importantly, when injected into the degenerated nucleus pulposus of human cadaveric intervertebral disk, the gel flowed into the clefts without leakage. This study demonstrates that 2.5% Protasan UP G213 cross-linked to 5% genipin might be a promising scaffold for disk tissue engineering.

Aged↗

PubMedDate not supplied

Anteroposterior centering of the humeral head on the glenoid in vivo.

BACKGROUND: The capsule and ligaments are generally viewed as the primary stabilizers of the glenohumeral joint, but many important activities are performed in midrange positions in which these structures are lax. HYPOTHESIS: In vivo, the humeral head can be centered in the glenoid, even when the shoulder is in positions in which the capsule is lax and even when the shoulder is passively positioned. STUDY DESIGN: Controlled laboratory study. METHODS: We documented the centering of the humeral head in the relaxed shoulders of six subjects using open-magnet magnetic resonance imaging scans. RESULTS: While these shoulders were passively placed in midrange positions (those not at the extremes of motion), the humeral head center was never more than 2.2 mm from the glenoid center (mean + 0.1 +/- 1.2 mm). CONCLUSIONS: The results suggest that mechanisms other than ligamentous restraint, such as the compressive effect of resting muscle tone into the conforming concavity of the glenoid, may be sufficient to maintain centering of the glenohumeral joint. Further exploration of these mechanisms may lead to methods other than ligament tightening or capsular shrinkage for restoration of stability to joints that are unstable in the midrange of motion. CLINICAL RELEVANCE: In that many patients with unstable shoulders demonstrate instability in midrange positions, it is hoped that further study of living shoulders will lead to a more effective understanding of the nonligament mechanisms of shoulder stability and the ways in which these stabilizing mechanisms can be restored.

Adult↗