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Biomedical subjects

W Macaulay

Publications and source records attributed to W Macaulay.

12 recordsLinked to original sources
PubMed2001

Nerve injury after primary total knee arthroplasty.

There is controversy about the incidence of and predisposing factors to the development of peripheral nerve palsy after total knee arthroplasty (TKA). In this study, 19 patients with a documented neurologic complication were identified after a retrospective review of 1,476 primary TKAs performed between January 1970 and December 1998 at the New York Presbyterian Hospital at Columbia University, for an overall incidence of 1.3%. Contrary to previously published data, valgus deformity, flexion contracture, the use of postoperative epidural anesthesia, the prolonged use of pneumatic tourniquets, and preexisting neuropathy were not associated with the development of peripheral neuropathy after TKA based on our data. A larger percentage of rheumatoid knees experienced a neurologic injury than was expected, however. No other significant risk factors for peripheral neuropathy after TKA were identified based on data from our patients. Immediately after discovery of the nerve palsy, conservative treatment was employed for each of our patients. All patients showed at least a partial recovery at the end of follow-up, with most experiencing a complete recovery from symptoms.

Adult↗
PubMed1998

Nitric oxide release by macrophages in response to particulate wear debris.

At the interface between a prosthetic implant and bone, macrophage interaction with particulate wear debris is a key event in the initiation of localized bone resorption, leading to aseptic loosening of the prostheses. Numerous investigators have reported that macrophages release a variety of cytokines and mediators including tumor necrosis factor, interleukin-1, prostaglandin E2, and interleukin-6 when they are stimulated with particulate wear debris. In this study, we have demonstrated that macrophages stimulated with particulate debris are also capable of releasing in copious amounts a key inflammatory chemical, nitric oxide. This release of nitric oxide was dependent upon the period of culture and the type and dosage of the challenging particles. Titanium-alloy particles were the most stimulatory, followed by commercially pure titanium and polymethyl-methacrylate. While the role of nitric oxide in osteolysis is not clearly understood, the literature suggests that it may be a key mediator in inhibiting DNA synthesis, in cell proliferation, and in stimulating PGE2 release. This finding enhances our understanding of the sequence of events occurring at the bone-implant interface during wear debris-mediated osteolysis, and exposes potential avenues to interrupt this sequence.

Animals↗
PubMed1997

Identification of inducible nitric oxide synthase in human macrophages surrounding loosened hip prostheses.

Exposure of rodent macrophages to certain cytokines and endotoxin results in the synthesis of inducible nitric oxide synthase (iNOS or NOS-II) leading to the production of large amounts of nitric oxide (NO). Cultures of human macrophages, in contrast, do not produce iNOS after cytokine stimulation, and their ability to act as a physiological source of NO remains questionable. Here we have used immunohistochemistry and in situ hybridization to demonstrate the presence of iNOS within human macrophages present in the interfacial membrane and pseudocapsule that surround failed prosthetic hip joints. Synovial tissue recovered from normal human joints did not express iNOS. Many of the iNOS-positive macrophages within the interfacial membrane had phagocytosed large amounts of polyethylene wear debris, suggesting a role for phagocytic stimuli in inducing iNOS in human macrophages. These findings additionally support a role for NO in modulating the localized bone resorption that accompanies the aseptic loosening of prosthetic joints.

Aged↗
PubMed1996

Suppression of antigen-induced arthritis in rabbits by ex vivo gene therapy.

Gene therapy offers a novel approach to treating human joint diseases such as rheumatoid arthritis. In the present study, we have used the retrovirus, MFG-IRAP, to transfer the human IL-1 receptor antagonist protein (IRAP) gene to rabbits' knees and have assessed its impact on inflammatory and chondrodestructive aspects of the acute phase of antigen-induced arthritis in these joints. Surprisingly, intra-articular expression of IRAP was three- to fivefold higher in arthritic knees than in nonarthritic knees, accumulating to levels of over 20 ng/knee in the highest expressing joints. This level of expression produced a marked chondroprotective effect but a milder anti-inflammatory one. Both the increased cartilage matrix catabolism and the inhibition of matrix synthesis that occur in antigen-induced arthritis were abrogated in the presence of the IRAP gene; the latter effect was particularly strong. Of the indices of inflammation that were examined, only leukocyte influx into the joint space was inhibited, and this effect declined with time. Concentrations of rabbit IL-1 were reduced by the IRAP gene, suggesting inhibition of an autocrine induction loop. These data demonstrate that the course of arthritic disease in the rabbit knee can be altered by genetic manipulation, thus encouraging the further development of gene treatments for human joint diseases.

Animals↗
PubMed1995

Aseptic loosening in uncemented total hip arthroplasty in a canine model.

An in vivo canine model was developed to investigate the histologic and biochemical parameters associated with aseptic loosening. Thirty-eight canines had cementless total hip arthroplasty. Experimental groups were designed specifically to investigate the relative contributions of implant motion and particulate debris (cobalt chrome alloy, titanium aluminum vanadium, and polyethylene) on the resultant periprosthetic tissues. Tissues from a stable, well-ingrown prosthesis provided a control. Importantly, the histologic and biochemical characteristics of the experimentally induced membranes consistently correlated with previous in vitro reports of tissues retrieved at revision surgery for aseptic loosening. Implant motion and all 3 particulate debris groups resulted in increased numbers of macrophages in the periprosthetic membranes. The histologic findings paralleled the increase in levels of biochemical mediators of bone resorption as measured by collagenase, gelatinase, prostaglandin E2, and interleukin-1 activity. The most striking results were seen in the histology and biochemistry of the particle groups with highly cellular membranes showing increased biochemical activity when compared with controls. The clinical relevance of this work lies in the description of an in vivo model of aseptic loosening that can be used to investigate the effects of numerous variables implicated in aseptic loosening. Ultimately, the model may serve as a basis for developing therapeutic interventions.

Alloys↗
PubMed1994

Peripheral neuropathies following total hip arthroplasty.

The authors reviewed the complication records following total hip arthroplasty at their institution between January 1976 and July 1989. Forty-two patients (12 men and 30 women) with 45 neurologic complications were identified following 7,133 consecutive total hip arthroplasties; an incidence rate of 0.63%. The average age of these patients was 58 years (range, 27-81 years). Thirty-four nerve injuries were noted in the lower extremity (0.48% incidence rate) and 11 in the upper extremity (0.15% incidence rate). The majority of patients (64%) with neurologic injury to the upper extremity had the diagnosis of inflammatory arthritis. The common peroneal was most often involved in the lower extremity. The ulnar nerve was most commonly involved in the upper extremity. The pathogenetic factors leading to neurologic injury in the majority of patients were not clearly established. Leg lengthening did not seem to be a major cause. The prognosis of patients with nerve palsy of the upper extremity is favorable compared with injury to the lower extremity. Similarly, the percentage of patients with a permanent neurologic deficit was lower in the primary surgery group (27%) compared with the revision/reoperation group (43%). The overall percentage of permanent nerve palsy was 33%. Female patients, for unclear reasons, appear to have a higher risk for neurologic injury. Also, the risk of neurologic injury following total hip arthroplasty appears to be higher with revisions/reoperations and with an inexperienced surgeon.

Adult↗
PubMed1994

Comparison of interface membranes obtained from failed cemented and cementless hip and knee prostheses.

Biochemical and histologic analyses were performed on interface membranes obtained at revision of aseptically loosened hip implants (n = 36) and knee implants (n = 16). Clinical failure occurred sooner in patients with uncemented total hip implants (Group 1) than in patients with cemented implants (Group 2) (p < 0.02). There was no difference in time to revision between the patients with uncemented implants (Group 3) and patients with cemented total knee implants (Group 4). Histologically, more small (< 5 mu) polyethylene particles were found within macrophages and fibroblasts in membranes from Groups 1 and 2. Polyethylene particles from failed total knees (> 10-100 mu) were larger than those from failed total hips. Large polyethylene fragments and foreign-body giant cells were more common in failed knees than failed total hip membranes. Biochemically, proteinase and cytokine activity in the tissue culture supernatant from all groups was higher than in the control tissue (p < 0.01). The activities of stromelysin, prostaglandin E2, interleukin-1 alpha, interleukin-1 beta, and tumor necrosis factor-alpha were higher in Groups 1 and 2 than in Groups 3 and 4 (p < 0.05). These findings support the hypothesis that interface membranes enveloping femoral (hip) and tibial (knee) components of failed total joint implants may promote bone resorption and aseptic loosening. The reason for slower failure of knee implants as compared with hip prostheses may be the lower level of biochemical activity and macrophage density that correlates closely with larger polyethylene particles.

Aged↗
PubMed1992

Antigenic properties of keratan sulfate: influence of antigen structure, monoclonal antibodies, and antibody valency.

The influence of (a) antigen structure, (b) type of monoclonal antibody, and (c) antibody bivalency on the immunochemical detection and quantification of keratan sulfate (KS) from aggrecan has been studied. Apparent KS epitope levels were determined by immunoglobulin G (IgG)-enzyme-linked immunosorbent assay (ELISA) in preparations of human aggrecan and in a defined series of lower molecular weight proteoglycan preparations generated by proteolytic and alkali treatment of aggrecan. Gel filtration chromatography showed KS epitope to be preferentially detected in the higher molecular weight fragments of the preparations. In single KS chains the epitope was detected in the chains of higher M(r). The ability of the proteoglycan to inhibit in the IgG-ELISA decreased with a reduction in proteoglycan fragment size, ranging between 6- and 260-fold, depending on the antibody used. This was considered to be a cooperative binding effect. With most antibodies, the sensitivity of the IgG-ELISA (represented by the steepness of the inhibition slope) was also reduced with smaller inhibitor sizes. The lowest limit of detectability (the amount of KS required to generate 20% inhibition) varied by up to 60-fold depending on the antibody used. The use of monovalent Fab fragments instead of the whole IgG anti-KS antibody in the ELISA showed that the bivalency of the antibody also affected the quantitation of the assay. In the Fab-ELISA the assay was found to have an increased detectability (by 9.5-fold with aggrecan as the inhibitor), and the proteoglycan fragments and aggrecan all generated parallel inhibition curves. Although the Fab-ELISA was somewhat influenced by the structural presentation of the KS, this was not apparent for small fragments and single chains. Thus the effects of cooperative binding and antibody valency could be overcome and quantitative data could be obtained for all samples, using papain-digested samples and the Fab-ELISA. Application of this assay to analysis of body fluids showed the KS-containing fragments in synovial fluid, serum, and urine were of different sizes and could be quantified.

Aggrecans↗
PubMed1987

The relation of predicted structure to observed conformation and activity of glucagon analogs containing replacements at positions 19, 22, and 23.

Six new analogs of glucagon have been synthesized containing replacements at positions 19, 22, and 23. They were designed to study the correlation between predicted conformation in the 19-27 segment of the hormone and the conformation calculated from circular dichroism measurements and the observed activation of adenylate cyclase in the liver membrane. The analogs were [Val19]glucagon, [Val22]glucagon, [Glu23]glucagon, [Val19,Glu23]glucagon, [Glu22,Glu23]glucagon, and [Ala22,Ala23]glucagon. The structures predicted for the 19-27 segment ranged from strongly alpha helical to weakly beta sheet. The observed conformations varied as functions of amino acid composition, solvent, concentration, pH, and temperature but did not correlate well with prediction. There was, however, a correlation between predicted structure and activation of adenylate cyclase in rat liver membranes.

Adenylyl Cyclases↗