Diagnostic value of transthoracic Doppler echocardiography in pulmonary hypertension: a meta-analysis.

BACKGROUND: A commonly used noninvasive method, transthoracic Doppler echocardiography (TDE) has been widely recommended for the diagnosis of pulmonary hypertension (PH). We aimed to review comprehensively the evidence for the use of TDE to diagnose PH. METHODS: After a systematic review of English-language studies, we used random-effects models to pool sensitivity, specificity, and other measures of accuracy of TDE for the diagnosis of PH. Summary receiver operating characteristic (SROC) curves were used to summarize overall test performance. RESULTS: Six studies met our inclusion criteria. The summary estimates for TDE in the diagnosis of PH in the included studies were as follows: sensitivity, 0.82 (95% confidence interval (CI), 0.76-0.88); specificity, 0.68 (95% CI, 0.64-0.72); positive likelihood ratio (PLR), 2.88 (95% CI, 1.77-4.70); negative likelihood ratio (NLR), 0.31 (95% CI, 0.18-0.53); and diagnostic odds ratio (DOR), 11.36 (95% CI, 4.62-27.94). CONCLUSIONS: Current evidence suggests that TDE is a test with acceptable mixed sensitivity, but in isolation, it has insufficient specificity for detecting PH. It may be useful as a first-line surveillance modality in patients in whom PH is suspected. The value of the combination of TDE with other noninvasive methods for PH detection warrants further investigation.

Ectopic expression of macrophage scavenger receptor MARCO in synovial membrane-like interface tissue in aseptic loosening of total hip replacement implants.

Macrophage receptor with collagenous structure (MARCO) is a scavenger receptor with a very limited expression in healthy tissues. It was hypothesized that foreign body wear debris induces it to participate in handling of implant-derived particles in human synovial membrane-like tissue around aseptically loosening total hip replacement implants. A DNA microarray study showed that MARCO was upregulated in human monocytes by polymethyl methacrylate particles in cell culture. MARCO mRNA and protein were strongly expressed in numerous CD68 positive macrophages and foreign body giant cells in interface membrane lining and stroma around cemented implants, but was only present in a few cells in synovial membrane from osteoarthritis patients. A 65-kDa MARCO-reactive band was only found in interface tissue extracts. This is the first work to show upregulation of MARCO mRNA by foreign bodies in vitro. This is paralleled in vivo as MARCO mRNA and protein were over-expressed in chronic foreign body synovitis. As scavenger receptor MARCO apparently participates in handling of wear particles, which due to their nondegradable, irritating nature initiate/perpetuate foreign body inflammation, and peri-implant osteolysis.

Human parainfluenza virus type 2 (HPIV2) induced host ADAM8 expression in human salivary adenocarcinoma cell line (HSY) during cell fusion.

BACKGROUND: The aim of the study was to investigate expression of ADAMs (A Disintegrin and A Metalloproteinase) of host cell origin during cell-cell fusion induced by human parainfluenza virus type 2 (HPIV2). RESULTS: Induction of host cell ADAM9 was observed in GMK cells, but the applicability of this model was restricted by lack of cross-reactivity of the anti-human ADAM8 antibodies with the corresponding green monkey antigens. HSG cells were not susceptible to HPIV2 virus infection. In contrast, in human parotid gland HSY cells, a natural host cell for paramyxoviruses, HPIV2 induced ADAM8 expression. ADAM8 staining increased dramatically over time from 7.9 +/- 3% at zero hours to 99.2 +/- 0.8% at 72 hours (p = 0.0001). Without HPIV2 the corresponding percentages were only 7.7% and 8.8%. Moreover, ADAM8 positive cells formed bi- (16.2%) and multinuclear cells (3.5%) on day one and the corresponding percentages on day three were 15.6% for binuclear and 57.2% for multinuclear cells. CONCLUSION: ADAM8, well recognized for participation in cell-to-cell fusion especially in osteoclast formation, is up-regulated upon formation of multinuclear giant cells after HPIV2 induction in HSY cells. The virus-HSY cell system provides a novel experimental model for study of the molecular mechanism of cell fusion events.

Increased collagen degradation around loosened total hip replacement implants.

OBJECTIVE: To assess collagen degradation and its relationship to some of the key collagenolytic proteinases in the aggressive synovial membrane-like interface tissue around aseptically loosened hip replacement implants. METHODS: The medical indication for the primary total hip replacement was osteoarthritis in all study patients. Samples from the study patients were compared with control synovial membranes obtained from trauma (hip fracture) patients. Proteoglycans were extracted with 4M guanidinium chloride. Denatured collagen in the remaining matrix was solubilized with alpha-chymotrypsin. Nonsoluble matrix and supernatant fractions were acid hydrolyzed before measurement of hydroxyproline. The proportion of soluble (in vivo-degraded) collagen of the total sample collagen content was calculated. Proteinases were stained using the avidin-biotin-peroxidase complex method. RESULTS: Collagen in the interface membrane from the implants was highly degraded (mean +/- SEM 20 +/- 3%) compared with that in the control synovial membranes (12 +/- 1%; P = 0.007). In controls, the degree of collagen degradation did not correlate with levels of matrix metalloproteinase 1 (MMP-1), MMP-13, or cathepsin K, although MMP-1 approached statistical significance. In interface membranes, the correlations were r = 0.88 (P = 0.002), r = 0.92 (P = 0.001), and r = 0.98 (P < 0.0001) for MMP-1, MMP-13, and cathepsin K, respectively. CONCLUSION: In normal synovial membrane, collagen matrix remodeling may be mainly an intracellular process. In contrast, pathologic tissue destruction in the interface membrane from prosthetic hip joints is associated with a shift toward MMP-13 and cathepsin K, which become activated and overcome their endogenous inhibitors (tissue inhibitors of metalloproteinases and cystatin C). The highly significant correlation between collagen degradation and cathepsin K indicates an extracellular role of this acidic endoproteinase, consistent with previous observations concerning the acidity of the interface membrane.