Sublaminar wiring stabilization to prevent adjacent segment degeneration after lumbar spinal fusion.

INTRODUCTION: Adjacent segment degeneration (ASD) is a complication of lumbar spinal fusion. There are some reports on the cause of this degeneration but none concerning its prevention. We performed sublaminar wiring stabilization to prevent ASD after posterolateral lumbar spinal fusion with instrumentation. The purpose of this study was to prospectively evaluate the efficacy of this procedure. PATIENTS AND METHODS: Between 2003 and 2004, 54 consecutive patients with lumbar spinal canal stenosis and multilevel instability of the lumbar spine underwent posterior decompression and posterolateral fusion with instrumentation. The mean age at the time of surgery was 66.7 +/- 1.3 years, and the mean follow-up period was 40.0 +/- 1.1 months, with a minimum of 29 months. Twenty-seven of the patients underwent conventional sublaminar wiring stabilization at the cephalad segment adjacent to the site of fusion to prevent ASD (group A), and the other 27 patients did not (group B). Some items were assessed, including clinical outcome using Japanese Orthopaedic Association (JOA) score, sagittal global lumbar alignment, and segmental motion in flexion-extension radiographs of the cephalad vertebral body adjacent to the site of fusion. RESULTS: There were no significant differences in JOA scores between two groups, but 2 patients in group B underwent subsequent surgery due to ASD. Sagittal lumbar alignment did not change in group A but was significantly decreased in group B. With respect to segmental motion in flexion-extension radiographs, group A showed a significant decrease from 6.9 degrees before surgery to 3.4 degrees after surgery, on the other hand group B showed a significant increase from 5.6 degrees before surgery to 8.4 degrees after surgery. CONCLUSIONS: In this study, it was suggested that sublaminar wiring stabilization significantly reduces the range of motion of the adjacent segment and preserves sagittal lumbar alignment, which lead to prevention of ASD. The clinical outcome of the subsequent surgeries is relatively poor, so it is important to prevent ASD by any prevention such as sublaminar wiring stabilization.

Analysis of muscle atrophy after hip fracture in the elderly.

OBJECTIVES: To examine the relationship between muscle atrophy, ambulatory ability, and fracture type, and to make a specific rehabilitation regimen for each fracture type. DESIGN: Observational study. SETTING: Public hospital. PARTICIPANTS: Consecutive patients (N=53) with hip fracture (mean age, 83.6y) who underwent operative treatment. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The ambulatory ability score and the cross-sectional areas of lower-limb muscles as measured on computed tomography scans. RESULTS: Muscle atrophy was not related to fracture type. Although the mean ambulatory ability score decreased significantly from 4.5+/-0.3 points prior to injury to 3.0+/-0.6 points 1 month postadmission, the degree of muscle atrophy was not associated with the decrease in ambulatory ability. CONCLUSIONS: It seems likely that other factors are more important than muscle atrophy and fracture type in determining recovery after surgical repair of a fracture and that there is no need for rehabilitation regimens based on fracture types.

G1-G2 aggrecan product that can be generated by M-calpain on truncation at Ala709-Ala710 is present abundantly in human articular cartilage.

To elucidate the specific function of m-calpain in the metabolism of aggrecan in human articular cartilage, the prevalence and localization of a large glycosaminoglycan-bearing aggrecan product generated by m-calpain in human osteoarthritis (OA) cartilage were investigated. Extracts of human OA articular cartilage were analysed by immunostaining using new polyclonal anti-VPGVA antiserum that detects the COOH terminal neoepitope IVTQVVPGVA(709) generated by m-calpain-related cleavage within the keratan sulphate rich region of human aggrecan. Immunoblotting analyses of aggrecan populations in guanidine hydrochloride-extracts showed that OA cartilages contained anti-VPGVA positive aggrecan products with the COOH terminal neoepitope ... VPGVA(709), resulting from truncation between the Ala(709)-Ala(710) m-calpain-related cleavage site. This aggrecan product consisted of two NH(2) terminal globular domain (G1 and G2) and KS side chains. Immunohistochemical staining showed that anti-VPGVA positive staining was localized within chondrocytes and spread to the surrounding interterritorial matrix. Confocal microscopic analysis showed subcellular colocalization of anti-VPGVA and anti m-calpain. These results indicate that the aggrecan product with the COOH terminal neoepitope VPGVA(709) is synthesized regularly by intracellular processing in chondrocytes, and is present abundantly as a limited form of aggrecan. M-calpain is the major candidate of the proteinase to generate this aggrecan product during the intracellular aggrecan processing.

Mature bovine articular cartilage contains abundant aggrecan that is C-terminally truncated at Ala719-Ala720, a site which is readily cleaved by m-calpain.

Extracts of normal mature articular cartilage contain aggrecan molecules which bear the G1 domain (the N-terminal globular domain of aggrecan) and are C-terminally truncated by proteolysis at a number of sites. A proportion of these molecules are generated by an aggrecanase and/or matrix-metalloproteinase-mediated cleavage in the IGD (interglobular domain between the G1 and G2 domains of aggrecan). However, the proteinase(s) responsible for formation of the majority of the larger G1-G2 and glycosaminoglycan-bearing truncated species is (are) unknown. N-terminal sequencing of aggrecan core fragments generated by m-calpain digestion of bovine aggrecan has identified four novel cleavage sites: one within the CS (chondroitin sulphate)-1 domain (at one or more of the bonds Ser1229-Val1230, Ser1249-Val1250, Ser1287-Val1288, Gly1307-Val1308 and Ser1346-Val1347), two within the IGD (at bonds Ala474-Ala475 and Gly365-Gly366) and one within the KS (keratan sulphate) domain (at Ala719-Ala720). A new monoclonal antibody (SK-28) to the C-terminal neoepitope at M710VTQVGPGVA719 showed that aggrecan products generated by this cleavage are present in high abundance in mature bovine articular cartilage extracts. We conclude that m-calpain, or an unidentified proteinase with the capacity to cleave at the same site, is active during aggrecan biosynthesis/secretion by mature chondrocytes or in the matrix of mature bovine articular cartilage in vivo.

Calpain inhibition by cerebrospinal fluid and effects of calpain on intrathecal nerve tissue.

STUDY DESIGN: The effects of calpain on intrathecal nerve tissue in the rabbit were investigated. OBJECTIVE: To evaluate the chemonucleolytic side effect of calpain on nerve tissue in the event of accidental intrathecal calpain injection. SUMMARY OF BACKGROUND DATA: Calpain has a degradative effect on proteoglycans, and as previously shown, it is associated with chemonucleolytic action in the rabbit. However, its effect on nerve tissue in the event of accidental intrathecal injection is not clear. METHODS: The inhibitory activity of cerebrospinal fluid against calpain was measured in human cerebrospinal fluid using mu-calpain, and in different cerebrospinal fluid fractions separated by molecular filtration. The presence of the endogenous calpain inhibitor, calpastatin, in human cerebrospinal fluid was examined by Western blotting with anticalpastatin antibody. After intrathecal application of calpain in rabbits, the spinal cord nerve tissue was examined by light microscopy. RESULTS: Cerebrospinal fluid inhibited the enzyme reaction of calpain at its normal concentration. Immunoblotting with anticalpastatin antibody did not yield positive staining. After the intrathecal application of calpain, there was no evidence of degeneration in the nerve tissue of the spinal cord. CONCLUSIONS: This study suggests that in the event of accidental intrathecal injection of calpain for chemonucleolysis, the enzyme activity of calpain will be neutralized by cerebrospinal fluid, and the calpain should not cause unwanted side effects in chemonucleolysis.

Synergistic induction of apoptosis of rheumatoid arthritis synovial cells by H(2)O(2) and N-acetyl-leucyl-leucyl-norleucinal.

The effects of proteolysis inhibitors on hydrogen peroxide (H(2)O(2))-induced apoptosis were examined in cultured human synovial cells of rheumatoid arthritis (RA) patients. RA synovial cells were resistant to apoptosis induced by H(2)O(2). In the presence of 100 microM N-acetyl-leucyl-leucyl-norleucinal (ALLN, known as calpain inhibitor 1 and also a proteasome inhibitor), but not N-acetyl-leucyl-leucyl-methioninal (ALLM), apoptotic cell death was elicited by 400 microM H(2)O(2) at a concentration that alone never induced cell death. ALLN induced the expression of tumor suppressor p53 protein and p21(WAF-1) protein, probably through inhibition of proteasome. H(2)O(2) further potentiated ALLN-induced p53 expression. H(2)O(2) appeared to activate c-Jun N-terminal kinase (JNK) as well as extracellular signal-regulated kinase (ERK) and AKT. After administration of H(2)O(2) and p53 induction by ALLN, we found that either one alone is insufficient to induce apoptosis of RA synovial cells but their combination synergistically does so. These results suggest that induction of p53 by ALLN may be potentially important for triggering H(2)O(2)-induced apoptosis processes in RA synovial cells.