Presentation of Mycobacterium abscessus infection following rhytidectomy to a UK plastic surgery unit.

We report the presentation of a patient to a UK plastic surgery unit with Mycobacterium abscessus infection following a facelift surgery in Southern India. Treatment was protracted requiring surgical debridement and 6 months of antibiotics including a 3-week hospital admission for intravenous antibiotic therapy. We describe the clinical presentation, diagnosis and treatment of this unusual microorganism with reference to more familiar pyogenic infections.

Invasive potential of human rheumatoid tenosynovial cells is in part MT1-MMP dependent.

PURPOSE: In rheumatoid arthritis, tenosynovial invasion of tendon is associated with an increased rate of tendon rupture and a worse clinical prognosis compared to noninvasive disease. Tendon is composed predominantly of type I collagen, which can be efficiently degraded by collagenolytic matrix metalloproteinases (MMPs), one of which, MT1-MMP, is membrane bound and inhibited by tissue inhibitor of metalloproteinase-2, but not by TIMP-1. The role of MT1-MMP in tendon disease is unknown. In this report, we investigate the potential role of MT1-MMP in invasion of tenosynovium into tendon. METHODS: Matched synovial specimens were obtained from different regions of the wrist in 36 rheumatoid patients having extensor tenosynovectomy in most instances. The tenosynovium that was removed was surrounding tendons (termed encapsulating) invading tendons (termed invasive), and wrist joint synovium. Samples of tenosynovium were tested for MT1-MMP using Western blotting, and the MT1-MMP activity was quantified using commercial assays. Next, a 3-dimensional collagen assay was created, using freshly isolated tenosynovium. Transwell collagen invasion assays were then performed, using isolated tenosynovial cells to determine MT1-MMP's effect on tendon invasion. RESULTS: The MT1-MMP was present in 9 of 10 joint samples, 4 of 6 encapsulating tenosynovial samples, and 5 of 5 invasive tenosynovial samples. Activity assays demonstrated that mean levels of active MT1-MMP produced by joint samples was 6.1 +/- 4.1 ng/mL; by encapsulating tenosynovium was 3.9 +/- 4.2 ng/mL, and by invasive tenosynovium was 6.2 +/- 1.1 ng/mL. The 3-dimensional gel assays demonstrated that cell invasion was reduced by the addition of TIMP-2 and GM-6001(a broad spectrum matrix metalloproteinase inhibitor) but not by TIMP-1. The addition of TIMP-2 to invasion assays reduced the mean number of cells that invaded the collagen membrane from 11 +/- 5 cells/field to 7 +/- 3 cells/field in treated samples (p = .04). CONCLUSIONS: Our results demonstrate that MT1-MMP is present in rheumatoid tenosynovium and that MT1-MMP facilitates tenosynovial cell invasion into a type I collagen matrix, suggesting that MT1-MMP plays a crucial role in tendon invasion. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Membrane type 1 matrix metalloproteinase is a crucial promoter of synovial invasion in human rheumatoid arthritis.

OBJECTIVE: A hallmark of rheumatoid arthritis (RA) is invasion of the synovial pannus into cartilage, and this process requires degradation of the collagen matrix. The aim of this study was to explore the role of one of the collagen-degrading matrix metalloproteinases (MMPs), membrane type 1 MMP (MT1-MMP), in synovial pannus invasiveness. METHODS: The expression and localization of MT1-MMP in human RA pannus were investigated by Western blot analysis of primary synovial cells and immunohistochemical analysis of RA joint specimens. The functional role of MT1-MMP was analyzed by 3-dimensional (3-D) collagen invasion assays and a cartilage invasion assay in the presence or absence of tissue inhibitor of metalloproteinases 1 (TIMP-1), TIMP-2, or GM6001. The effect of adenoviral expression of a dominant-negative MT1-MMP construct lacking a catalytic domain was also examined. RESULTS: MT1-MMP was highly expressed at the pannus-cartilage junction in RA joints. Freshly isolated rheumatoid synovial tissue and isolated RA synovial fibroblasts invaded into a 3-D collagen matrix in an MT1-MMP-dependent manner. Invasion was blocked by TIMP-2 and GM6001 but not by TIMP-1. Invasion was also inhibited by the overexpression of a dominant-negative MT1-MMP, which inhibits collagenolytic activity and proMMP-2 activation by MT1-MMP on the cell surface. Synovial fibroblasts also invaded into cartilage in an MT1-MMP-dependent manner. This process was further enhanced by removing aggrecan from the cartilage matrix. CONCLUSION: MT1-MMP serves as an essential collagen-degrading proteinase during pannus invasion in human RA. Specific inhibition of MT1-MMP-dependent invasion may represent a novel therapeutic strategy for RA.

Advances in the modulation of cutaneous wound healing and scarring.

Cutaneous wounds inevitably heal with scars, which can be disfiguring and compromise function. In general, the greater the insult, the worse the scarring, although genetic make up, regional variations and age can influence the final result. Excessive scarring manifests as hypertrophic and keloid scars. At the other end of the spectrum are poorly healing chronic wounds, such as foot ulcers in diabetic patients and pressure sores. Current therapies to minimize scarring and accelerate wound healing rely on the optimization of systemic conditions, early wound coverage and closure of lacerations, and surgical incisions with minimal trauma to the surrounding skin. The possible benefits of topical therapies have also been assessed. Further major improvements in wound healing and scarring require an understanding of the molecular basis of this process. Promising strategies for modulating healing include the local administration of platelet derived growth factor (PDGF)-BB to accelerate the healing of chronic ulcers, and increasing the relative ratio of transforming growth factor (TGF)beta-3 to TGFbeta-1 and TGFbeta-2 in order to minimize scarring.