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The disruption of the extracellular disc matrix is a major hallmark of disc degeneration. This has previously been shown to be associated with an up-regulation of major matrix metalloproteinase (MMP) expression and activity. However, until now hardly any data are available for MMP/TIMP regulation and thereby no concept exists as to which MMP/TIMP plays a major role in disc degeneration. The objective of this study was, therefore, to identify and quantify the putative up-regulation of MMPs/TIMPs on the mRNA and protein level and their activity in disc material in relation to clinical data and histological evidence for disc degeneration. A quantitative molecular analysis of the mRNA expression levels for the MMPs (MMPs-1, -2, -3, -7, -8, -9, -13) and the MMP inhibitors (TIMPs-1 and -2) was performed on 37 disc specimens obtained from symptomatic disc herniation or degeneration. In addition, disc specimens from patients without disc degeneration/herniation (=controls) were analyzed. Expression of MMPs-1, -2, -3, -7, -8, -9, -13 and TIMPs-1, -2 was analyzed using quantitative RT-PCR, normalized to the expression level of a house keeping gene (GAPDH). Gene expression patterns were correlated with MMP activity (in situ zymography), protein expression patterns (immunohistochemistry), degeneration score (routine histology) and clinical data. MMP-3 mRNA levels were consistently and substantially up-regulated in samples with histological evidence for disc degeneration. A similar but less pronounced up-regulation was observed for MMP-8. This up-regulation was paralleled by the expression of TIMP-1 and to a lesser extent TIMP-2. In general, these findings could be confirmed with regard to protein expression and enzyme activity. This study provides data on the gene and protein level, which highlights the key role of MMP-3 in the degenerative cascade leading to symptomatic disc degeneration and herniation. Control of the proteolytic activity of MMP-3 may, therefore, come into the focus when aiming to develop new treatment options for early disc degeneration. [ABSTRACT FROM AUTHOR]

Health care expenditures are substantially increasing within the last two decades prompting the imperative need for economic evaluations in health care. Historically, economic evaluations in health care have been carried out by four approaches: (1) the human-capital approach (HCA), (2) cost-effectiveness analysis (CEA), (3) cost-utility analysis (CUA) and (4) cost-benefit analysis (CBA). While the HCA cannot be recommended because of methodological shortcomings, CEA and CUA have been used frequently in healthcare. In CEA, costs are measured in monetary terms and health effects are measured in a non-monetary unit, e.g. number of successfully treated patients. In an attempt to develop an effectiveness measure that incorporates effects on both quantity and quality of life, so-called Quality Adjusted Life Years (QUALYs) were introduced. Contingent valuation surveys are used in cost-benefit analyses (CBA) to elicit the consumer's monetary valuations for program benefits by applying the willingness-to-pay approach. A distinguished feature of CBA is that costs and benefits are expressed in the same units of value, i.e. money. Only recently, economic evaluations have started to explore various spinal interventions particularly the very expensive fusion operations. While most of the studies used CEA or CUA approaches, CBAs are still rare. Most studies fail to show that sophisticated spinal interventions are more cost-effective than conventional treatments. In spite of the lack of therapeutic or cost-effectiveness for most spinal surgeries, there is rapidly growing spinal implant market demonstrating market imperfection and information asymmetry. A change can only be anticipated when physicians start to focus on the improvement of health care quality as documented by outcome research and economic evaluations of cost-effectiveness and net benefits. [ABSTRACT FROM AUTHOR]