Localized osteolysis in stable, non-septic total hip replacement

We are reporting four cases of extensive, localized bone resorption adjacent to a rigidly anchored, cemented total hip replacement. None of these hips showed evidence of infection on clinical, bacteriological, or pathological evaluation. The tissue from the regions of osteolysis showed sheets of macrophages and foreign-body giant cells invading the femoral cortices. Abundant methylmethacrylate particulate debris was present in the tissues, but polyethylene wear debris was absent. The histological appearance of this tissue resembled that reported about loosened total hip implants with the exception of the synovial-like layer at the cement surface. The cases reported here show that aggressive bone lysis may occur around stable cemented total hip arthroplasties without the presence of sepsis or malignant disease.     

Focal glomerulosclerosis in the remnant kidney model--an inflammatory disease mediated by cytokines

BACKGROUND: The mechanism of progression of established renal disease remains unclear. While a low protein diet slows this progression, the role of cytokines in this process has been little investigated. METHODS: We investigated cytokine expression by Northern blot and immunohistochemistry in two groups of 5/6 nephrectomized rats (5/6 Nx) fed a normal (24%) or low (6%) protein diet and compared them with sham operated controls. RESULTS: The rats on 6% protein diet had significantly less focal glomerulosclerosis (FGS) (17.4 +/- 4.4 vs 27.4 +/- 8.8%, P < 0.05) and global sclerosis (GGS) after 7 weeks (0.4 +/- 0.8 vs 3.5 +/- 2.1% of glomeruli P < 0.05). Both experimental groups showed three times control levels of MCP-I expression after 2 weeks. However in the 5/6 Nx 6% protein group the expression decreased at 4 weeks (1.5 times controls) and reached control levels after 7 weeks. In contrast, the 5/6 Nx 24% protein group exhibited a further marked increase after 4 weeks (5.6 times controls) and was still two-fold higher after 7 weeks. TGF-beta expression was modestly but consistently increased at all time points (120-160% of controls), with no difference between the two study groups. Neither IL-1 beta or TNF-alpha was detectable at any time. Immunohistochemistry demonstrated TGF-beta intracellularly in distal tubular cells in both experimental and control animals, while MCP-1 protein was found in the area of FGS and in the apical pole of distal tubular cells in both experimental groups. Glomerular and interstitial ED1 positive cells were significantly increased after four weeks in the 5/6 Nx 24% protein group (P < 0.05). CONCLUSIONS: A 'mechanical' injury to the kidney clearly results in an inflammatory response associated with the upregulation of MCP-1. A low protein diet modulates the expression of MCP-1 and improves the morphological sequelae seen after renal ablation.      

Noninvasive measurement of systemic vascular resistance using Doppler echocardiography.

BACKGROUND: Systemic vascular resistance (SVR) is an integral therapeutic component of patients with heart failure and shock. We hypothesized that the ratio of the peak mitral regurgitant velocity (MRV) (m/s) to left ventricular outflow time-velocity integral (TVI(LVOT)) (cm) by Doppler would provide a noninvasive correlate of SVR. METHODS: SVR was correlated to MRV/TVI(LVOT) in 33 patients undergoing right heart catheterization. Receiver operating characteristic curves were generated to determine the best-balanced sensitivity and specificity to identify SVR > 14 Wood units (WU) and <10 WU. RESULTS: MRV/TVI(LVOT) correlated well with SVR (r = 0.842, 95% confidence interval 0.7-0.92, P <.001, Y = 0.459 + 49.397*X). By receiver operating characteristics, MRV/TVI(LVOT) > 0.27 had a 70% sensitivity and a 77% specificity to identify SVR > 14 WU. MRV/TVI(LVOT) < 0.2 had a 92% sensitivity and a 88% specificity to identify SVR < 10 WU. CONCLUSION: Doppler echocardiography provides a reliable noninvasive assessment of SVR.     

Teilzulassung – neue Gestaltungsmöglichkeit ohne praktische Bedeutung?

Ohne Zusammenfassung     

Inhibition of Complement Regulation Is Key to the Pathogenesis of Active Heymann Nephritis

Crry (complement receptor 1–related protein/gene y) is a key cellular complement regulator in rodents. It is also present in Fx1A, the renal tubular preparation used to immunize rats to induce active Heymann nephritis (HN), a model of membranous nephropathy. We hypothesized that rats immunized with anti-Fx1A develop autoantibodies (auto-Abs) to Crry as well as to the megalin-containing HN antigenic complex, and that anti-Crry Abs promote the development of injury in HN by neutralizing the complement regulatory activity of Crry. Rats immunized with Fx1A lacking Crry remained free of proteinuria and glomerular deposits of C3 during a 10-wk follow-up despite typical granular immunoglobulin (Ig)G deposits in glomeruli. Anti-Fx1A auto-Abs were present in their sera at levels that were not different from sera pooled from proteinuric rats with HN induced with nephritogenic Fx1A. Passive administration of sheep anti-Crry Abs to rats immunized with Crry-deficient Fx1A led to proteinuria and glomerular C3 deposition, which were not seen in such rats injected with preimmune IgG, nor in rats with collagen-induced arthritis injected with anti-Crry IgG. To directly examine the role of Crry in HN, rats were immunized with Crry-deficient Fx1A reconstituted with rCrry. This led to typical HN, with 8 out of 15 rats developing proteinuria within 14 wk. Moreover, the extent of glomerular C3 deposition correlated with proteinuria, and anti-Crry Abs were present in glomerular eluates. Thus, Crry is a key nephritogenic immunogen in Fx1A. Formation of neutralizing auto-Abs to Crry impairs its function, leading to unrestricted complement activation by Abs reactive with the HN antigenic complex on the epithelial cell surface.