Expression profiling of metalloproteinases and inhibitors in cartilage

Objective   To profile the expression of all known members of the matrix metalloproteinase ( MMP ), a disintegrin and metalloproteinase with thrombospondin motifs ( ADAMTS ), and tissue inhibitor of metalloproteinases ( TIMP s) gene families in normal cartilage and that from patients with osteoarthritis (OA).
Methods   Human cartilage was obtained from femoral heads at joint replacement for either osteoarthritis or following fracture to the neck of femur. Total RNA was purified and expression of genes assayed using quantitative real-time PCR.
Results   Several members of the above gene families were regulated in OA. Genes increasing in expression in OA were: at P  < 0.001, MMP-13 , MMP-28 , ADAMTS-16 ; at P  < 0.01, MMP-9 , MMP-16 , ADAMTS-2 , ADAMTS-14 and at P  < 0.05, MMP-2 , TIMP-3 , ADAMTS-12 . Genes decreasing in expression in OA were: at P  < 0.001, MMP-1 , MMP-3 , ADAMTS-1 ; at P  < 0.01, MMP-10 , TIMP-1 , ADAMTS-9 and at P  < 0.05, TIMP-4 , ADAMTS-5 , ADAMTS-15 . Correlation analysis revealed that groups of genes across the gene families are co-expressed in cartilage.
Conclusion   This is the first comprehensive expression profile of all known MMP , ADAMTS and TIMP genes in cartilage. Patterns of expression provide a foundation on which to understand mechanisms of gene regulation in OA and potentially for refining the specificity of anti-proteolytic therapies.     

Not an equal opportunity disease – a sex and gender-based review of colorectal cancer in men and women: Part II

This paper reviews the literature on colorectal cancer from a sex and gender-based perspective. Colorectal cancer is a major cause of death in the developed world, with rates increasing in developing countries. Although described by some writers as an ‘equal opportunity’ disease, it presents more risk to men than women. Both biological, or sex-linked factors, and gender-linked factors play a part in the aetiology of the disease, while gender differences in the use of screening and treatment also help shape the mortality gap between women and men for this condition. Without an appreciation of the part played by sex and gender in the risk of colorectal cancer, and without a gender-sensitive approach to screening in particular, it is possible that the mortality gap between men and women for this condition will widen in the future.     

Difficult myotomy is not determined by preoperative therapy and does not impact outcome.

OBJECTIVES: The impact of preoperative endoscopic therapy on the difficulty of laparoscopic Heller myotomy and the impact of the difficulty of the myotomy on long-term outcome has not been determined. This study was undertaken to determine whether preoperative therapy impacts the difficulty of laparoscopic Heller myotomy and whether preoperative therapy or difficulty of myotomy impacts long-term outcomes. METHODS: Since 1992, 305 patients, 56% male, median age 49 years, underwent laparoscopic Heller myotomy and were prospectively followed. The difficulty of the laparoscopic Heller myotomy was scored by the operating surgeon for the most recent 170 consecutive patients on a scale of 1 (easiest) to 5 (most difficult). Patients scored their symptoms before and after myotomy using a Likert scale from 0 (never/not bothersome) to 10 (always/very bothersome). RESULTS: Before myotomy, 66% of patients underwent endoscopic therapy: 33% dilation, 11% Botox, and 22% both. Preoperative endoscopic therapy did not correlate with the difficulty of the myotomy (P=NS). Median follow-up was 25 months. Regardless of the difficulty of the myotomy, dysphagia improved with myotomy (P<0.0001). By regression analysis, the frequency and severity of post-myotomy dysphagia correlated with neither preoperative endoscopic therapy nor the difficulty of the myotomy. CONCLUSIONS: Laparoscopic Heller myotomy improves the frequency and severity of dysphagia. The difficulty of laparoscopic Heller myotomy is not impacted by preoperative therapy, and neither preoperative therapy nor difficulty of the myotomy impact long-term outcome.