Objective. To quantify the inflammatory cell response in rat air pouch pseudosynovial membrane during monosodium urate monohydrate (MSU) crystalinduced inflammation.Methods. In the rat air-pouch model, we used a computer-assisted histomorphometric method to quantify cell distributions, based on cell linear densities, in histologic sections of membranes from pouches injected with MSU or saline. The volume, white blood cell (WBC) count, and histamine content of the pouch exudates were determined at several time points.Results. Injection of 10 mg of MSU crystals into the pouch produced an acute exudate. After peaking at 24 hours, the exudate volume and WBC count decreased spontaneously over the next 3 days, simulating the self-limited course of acute gout. Membrane thickness followed a parallel course. Membrane polymorphonuclear cell (PMN) linear densities were closely correlated with exudate WBC counts, suggesting PMN recruitment from the subintimal synovial membrane. Both monocyte/macrophage and mast cell linear densities increased in the subintimal layer 2 hours after crystal injection (P ‫؍‬ 0.038 and P ‫؍‬ 0.03, respectively, versus controls), whereas PMN linear densities showed 2 peaks, one at 4 hours and the other 24 hours. The exudate histamine content peaked 6 hours after crystal injection, when mast cell linear densities were minimal in the membranes, suggesting mast cell degranulation.Conclusion. An increase in monocyte/macrophage and mast cell densities in the membrane preceded the PMN influx in the pouch membrane and exudate, suggesting that mast cells may be involved in the early phase of MSU crystal-induced inflammation, at least in this rat model.The pathogenesis of acute gout has been addressed in many studies. Synthetic monosodium urate monohydrate (MSU) crystals have been injected into the tissues or joints of various animals, including dogs (1), rats (2), mice (3), and rabbits (4). These in vivo experiments have elucidated the kinetics of acute-phase proteins, cytokines, and polymorphonuclear cell (PMN) and mononuclear cell (MNC) contents in exudates, showing a peak in cell recruitment and demonstrating that the acute phase was followed by self-limitation of the MSU crystal-induced inflammation. In vitro studies have shown that MSU crystals added to various cell cultures (5) induced time-and dose-dependent cytokine secretion. Schumacher et al (1) and Gordon et al (6) have reported evidence that acute gout is initiated by phagocytosis of free MSU crystals by the lining cells (type A [macrophage-like] synovial cells). This event is currently acknowledged to precede synovial inflammation per se (7,8). However, little is known about the kinetics of the cellular events within the synovial membrane.

W e compared and quantified the modes of failure and patterns of wear of 11 Mittelmeier and 11 Ceraver-Ostal retrieved alumina-alumina hip prostheses with reference to the corresponding clinical and radiological histories.Macroscopic wear was assessed using a three-dimensional co-ordinate measuring machine. Talysurf contacting profilometry was used to measure surface roughness on a microscopic scale and SEM to determine mechanisms of wear at the submicron level.The components were classified into one of three categories of wear: low (no visible/measurable wear), stripe (elliptical wear stripe on the heads and larger worn areas on the cups) and severe (macroscopic wear, large volumes of material lost). Overall, the volumetric wear of the alumina-alumina prostheses was substantially less than the widely used metal and ceramic-on-polyethylene combinations. By identifying and eliminating the factors which accelerate wear, it is expected that the lifetime of these devices can be further increased. The long-term effects of ultra-high-molecular-weight polyethylene (UHMWPE) wear debris and the resulting osteolysis are well documented and have prompted renewed interest in alternative materials for total hip arthroplasty (THA). The alumina-alumina bearing couple was introduced in 1970, 1 but has been used only in small numbers compared with standard metal-on-UHMWPE designs. Laboratory tests and simulator studies have demonstrated the low friction and wear of this prosthesis, but concerns remain about its performance in vivo. Published clinical studies have already established the safety and the good tribological performance of this couple, 2-5 but there are doubts about the long-term performance of aluminaalumina THAs. The most common reasons for revision have been loosening of one or both components. The mechanisms which have led to this loosening have not yet been satisfactorily explained and therefore clinical and retrieval studies are needed to assess the performance of these prostheses in vivo. It is still unclear what role, if any, wear and wear debris play in their long-term performance or indeed if wear is a factor in the loosening process. Our aim was to establish the wear patterns and rates of wear of two different alumina-alumina prostheses to allow future improvements in design and materials. Patients and MethodsExplants. We studied two series of explants from centres in the UK and France. The UK series consisted of 11 explanted bearing couples from a 16-year series of Mittelmeier THAs implanted between 1980 and 1996 at Bradford Royal Infirmary by Mr A. Nevelos. The French series consisted of 11 explanted Ceraver-Osteal bearings implanted between 1977 and 1988 at the Hospital St Louis, Paris, by Professor L. Sedel and Professor Witvoet. Design of the prosthesis. The Mittelmeier Autophor (Ceramtec AG, Plochingen, Germany) design consisted of an externally threaded truncated cone socket made of monolithic alumina ceramic which was screwed into an underreamed acetabulum to articulate with a 32 or 38 mm modular he...

Objective. We investigated the effects of transforming growth factor Pl (TGFP1) on monosodium urate monohydrate (MSU) crystal-induced acute inflammation in vivo.Methods. One hour after MSU crystal-induced acute inflammation was produced in the rat subcutaneous air pouch model, the effects of recombinant human TGFPl (rHuTGFP1; 10-100 pglanimal) and ultrapure TGFPl (UPTGFPI; 100 and 500 pglanimal) were assessed, based on absolute and differential white blood cell counts in the exudate. The effects of 10 pg of rHuTGFP1 preincubated with a specific anti-TGFP antibody, and the effects of coinjection of crystals and rHuTGFP1, were also studied.Results. UPTGFPl and rHuTGFPl markedly reduced MSU crystal-induced inflammation. Recombinant human TGFPl also reduced inflammation when administered concomitantly with MSU crystals. Moreover, rHuTGFPl and UPTGFP1, injected l hour after MSU crystal injection, reduced the inflammatory response in a dose-dependent manner. Injection of rHuTGFPl (100 pglanimal) resulted in a >9w0 reduction in the maximal white blood cell count, achieved 6 hours after Spontaneous resolution is an important clinical feature of gouty attacks that is not yet fully understood (1,2). Lowering of pH and stimulation of phagocyte oxidative metabolism during crystal-induced inflammation may promote monosodium urate monohydrate (MSU) crystal dissolution. However, this cannot entirely explain the self-limited nature of gouty inflammation, since MSU crystals can remain in the synovial fluid after acute inflammation and have been identified in noninflammatory synovial fluids from gout patients (3).In vitro (4) and in vivo ( 5 ) studies have shown that changes in the protein coating of MSU crystals and in other as-yet-unidentified components that are generated locally during subsiding inflammation probably contribute to the self-limited nature of acute gouty arthritis (6). There is strong in vitro evidence that proinflammatory cytokines such as interleukin-lP (ILlP), tumor necrosis factor P (TNFP), IL-6, and IL-8 (7-1 1) are released within hours when monocytes and macrophages are incubated with MSU crystals. Natural cytokine inhibitors such as IL-1 receptor antagonist (IL-1Ra) and/or soluble TNFa receptor, or other regulatory cytokines such as IL-4 and IL-10, may block acute and subsequent chronic inflammation.