Factors affecting paramagnetic contrast enhancement in synovial fluid: effects of electrolytes, protein concentrations, and temperature on water proton relaxivities from Mn ions and Gd chelated contrast agents.

INTRODUCTION: Protein and electrolyte concentration of synovial fluid (SF) varies with the type of underlying arthritis. These characteristics can be utilized by magnetic resonance technology to provide a potentially significant diagnostic modality through quantitative assessments of inherent water relaxation rates and their response to contrast agents. METHODS: We evaluated the effect of a classic "in vitro" contrast agent, the Mn ion, and a common "in vivo" gadolinium based contrast agent, gadopentetate dimeglumine, on the water relaxation times of solutions with biochemical compositions simulating different types of arthritis along with similar studies of SF obtained from patients. RESULTS: The results demonstrate how protein and electrolyte concentrations play a significant role in the response of water relaxation to the Mn ion but much less so to chelated gadolinium contrast agents used clinically. DISCUSSION: A major challenge remains to develop paramagnetic agents with less toxicity than the Mn ion but with similar properties that can then serve as a tool to determine protein concentrations through imaging and thereby assist in the diagnosis of inflammatory arthrides and evaluation of therapeutic regimens.

Investigation of the activation of a human serum complement protein, C3, by orthopedic prosthetic particulates.

Myriad molecular, cellular, and physiological processes underlie the inflammatory and osteolytic processes induced by particles of biomaterials resulting from the wear of implants such as total joint replacement prostheses. The objective this study was to investigate the role that the complement system may be playing in these phenomena. The aim was to evaluate the degree to which particles of selected orthopaedic materials--high density and ultrahigh molecular weight polyethylene, polymethylmethacrylate, and commercially pure titanium--cause the elevation of a key complement molecule, C3a, in an in vitro assay that directly measured the concentration of C3a. The results demonstrated that HDPE particles, at high concentration, are capable of causing the elevation of C3a in the in vitro assay. This finding is discussed in the context of other work and the mechanics of the complement system as it may affect the osteolytic process.

Effect of mechanical perturbation on the release of PGE(2) by macrophages in vitro.

Macrophages play numerous roles in both physiologic and pathologic processes. Along with fibroblasts, they comprise the synovial tissue that forms the lining of musculoskeletal joint capsules and bursae, and they often envelop implants. During the process of phagocytosing prosthesis-related particles, macrophages in peri-implant tissue release inflammatory mediators. Little is known, however, about the response of these cells to mechanical perturbation, which often is a component of the physical environment of the cell. Mouse peritoneal macrophages were grown on a flexible membrane in vitro and a dynamic 1-Hz spatially uniform sinusoidal strain pattern imparted to the elastomeric substrate. The effect of mechanical strain on prostaglandin (PG) E(2) release was evaluated using cells that were activated by lipopolysaccharide (LPS) as well as by those that were not. The results are compared with the levels of PGE(2) stimulated by metallic particles. Strain magnitudes of 4 and 8% applied for 1 h resulted in almost a twofold increase in the release of PGE(2) from LPS-stimulated cells (p < 0.05) and nonstimulated macrophages (p < 0.07), compared with nonperturbated controls. No release was elicited by a challenge of metal particles. These findings demonstrate for the first time an effect of mechanical force on the release of an inflammatory mediator by macrophages. This response may help to explain the macrophage-mediated processes underlying the osteolysis associated with loose prostheses in bone and suggests a mechanism for the inflammation of synovial tissues by excessive mechanical strain.

Peripheral blood lymphocytes in SLE--hyperexpression of CD154 on T and B lymphocytes and increased number of double negative T cells.

Abnormalities in the regulation of both cell-mediated and humoral immunity have been implicated in the pathophysiology of systemic lupus erythematosus (SLE). Cognate contact-dependent T-B cell interactions involving CD154 (CD40 ligand) on activated T cells and CD40 on B lymphocytes have a critical role in antibody production. Abnormal CD154 expression on lymphocytes may play a role in the production of potentially pathogenic autoantibodies and defects in self-tolerance mechanisms may be important. Failure of intrathymic or peripheral deletion of autoreactive T cells may also result in an autoimmune phenotype. Elevated levels of CD3(+)CD4(-)/8(-) (double negative) T cells (DNT) in the peripheral blood are a surrogate marker for defects of this type. The expression of CD154 on T and B cells was evaluated and levels of double negative T cells in the peripheral blood were assessed by two and three colour flow cytometric analyses. We studied peripheral blood lymphocytes in 48 patients with SLE. Twenty-five normal subjects and 12 patients with rheumatoid arthritis (RA) were studied as disease controls. T cells in 22/48 (45%) lupus patients expressed CD154 between 20-80% (median=52%). In normal controls and RA patients 8-18% T cells were CD154(+). Twelve patients (30%) had elevated expression of CD154 (20-50%) on B cells. In the control RA patients, less than 15% T cells were CD154(+). Twelve of 48 SLE patients had elevated numbers of DNT cells (18-27%). The control subjects had DNT cell numbers <10. These observations suggest that defects in either the intrathymic or peripheral deletion of potentially pathogenic T lymphocytes may play a role in the pathogenesis of SLE. The high expression of CD154 on both T and B cells may also be important in mediating the production of potentially harmful autoantibodies.

Update on nerve palsy associated with total hip replacement.

Nerve palsy is an uncommon but acknowledged complication of total hip replacement. The overall prevalence is approximately 1%. The sciatic nerve, or the peroneal division of the sciatic nerve, is involved in nearly 80% of cases. The risk of nerve palsy in association with total hip replacement is increased for female compared with male patients, with a diagnosis of developmental dysplasia, and with patients undergoing revision surgery. In the majority of cases, the origin of the palsy is unknown. Because peripheral nerves are sensitive to compression, unrecognized compression may play a role in these cases. The prognosis for neurologic recovery is related to the degree of nerve damage. Complete, or essentially complete, recovery occurs in approximately 41% and another 44% have only a mild deficit. Approximately 15% have a poor outcome characterized by weakness that limits ambulation and/or persistent dysesthesia. Patients with some motor function immediately after the operation and those who recover some motor function within approximately 2 weeks of surgery have a good prognosis for recovery. In general, recovery of femoral nerve palsies is more predictable than that of sciatic palsies.