Muscle hypoxia in rheumatoid hands: does it play a role in ulnar drift?

PURPOSE: The cause of ulnar drift in patients with rheumatoid arthritis (RA) is unknown. It may occur because of external forces applied to the fingers during normal use. Alternatively, it may arise after changes in the internal forces on the anatomy of the digits owing to alterations in the supporting structures of the joints or their control mechanisms, or both. Intrinsic muscle tightness, which is commonly seen in RA hands, may be the result of adaptive shortening or a direct consequence of RA. Previous studies carried out by our group have shown that joints, tendons, and associated synovium in RA hands are consistently hypoxic. Therefore, we formed the hypothesis that there is a difference in hand/forearm muscle oxygen tension in RA versus non-RA. METHODS: We measured tissue oxygen levels in the intrinsic muscles of the hands and forearm muscles of 29 patients with a diagnosis of RA, who were undergoing elective surgery. We measured oxygen levels using a microelectrode technique. A total of 31 patients without RA undergoing elective surgery served as matched controls. RESULTS: Our results show that the intrinsic muscles of RA patients are significantly more hypoxic than in non-RA controls. Moreover, there is a trend in the RA group for increasing hypoxia in a radial-to-ulnar direction when comparing the different intrinsic muscle groups. We also demonstrate that forearm and thenar and hypothenar muscles are significantly more hypoxic in RA versus non-RA patients. CONCLUSIONS: The intrinsic muscle weakness, intrinsic tightness, and muscle wasting observed in RA may not be due to disuse atrophy resulting from joint disease. From our data, we speculate that these changes may be the result of direct muscular involvement in RA leading to muscle hypoxia

Gene expression studies to investigate disease mechanisms in rheumatoid arthritis: Does angiogenesis play a role?

Gene expression studies represent a new and challenging approach that allows molecular dissection of complex diseases such as rheumatoid arthritis (RA). Optimally, gene analysis should be conducted in isolated populations of cells so that the differential gene expression may be directly correlated with transcription of genes. RA fibroblasts constitute the majority of the expanding synovial cell mass in the RA joint, and alterations in their phenotype are likely to be important in the pathogenic process. However, RA involves many cell types from tissues adjacent to the synovium and the important cell types are not known. Analysis of gene expression profiles by processing a complex tissue such as whole paws can provide useful information about dysregulated genes, not only in the synoviocytes but also in other, neighbouring cells (monocytes, osteocytes and chondrocytes) that may contribute to disease pathology. This review will focus on the use of gene expression studies, both in isolated cells and in whole tissue, as a means of studying the molecular mechanisms involved particularly in the angiogenic process in RA. In particular, we will focus on synovial angiogenesis, since the synovial vascular density is altered in RA. This will provide an increased surface area for inflammatory cell trafficking, as well as delivering nutrients and oxygen to the proliferating synovial cells. Therapeutic approaches targeting angiogenic factors such as vascular endothelial growth factor (VEGF), which is increased in RA, have already shown some clinical success in oncology, and in mouse models of arthritis. © 2007 Bentham Science Publishers Ltd

Angiogenesis and plastic surgery.

SUMMARY: Angiogenesis, the formation of new blood vessels from an existing vascular bed, is a normal physiological process which also underpins many--apparently unrelated--pathological states. It is an integral factor in determining the success or failure of many procedures in plastic and reconstructive surgery. As a result, the ability to control the process would be of great therapeutic benefit. To appreciate the potential benefits and limitations of recent advances in our understanding of angiogenesis, it is important to comprehend the basic physiology of blood vessel formation. This review aims to summarise current knowledge of the way in which angiogenesis is controlled and to look at how disordered vessel development results in pathology relevant to plastic surgery. Through this we hope to provide a comprehensive overview of the recent advances in angiogenesis as they relate to plastic surgery, particularly the promotion of flap survival, tendon healing, nerve regeneration, fracture healing and ulcer treatments

Synovial hypoxia as a cause of tendon rupture in rheumatoid arthritis.

PURPOSE: Hypoxia and angiogenesis are now recognized as being important events in the perpetuation of joint destruction in rheumatoid arthritis (RA). In 50% of patients with RA, however, the disease also involves inflammation of the synovial tissue surrounding the tendons, which is associated with multiple ruptures and poor prognosis for long-term hand function. The aim of this study was to determine whether hypoxia and angiogenesis may also play a role in RA tendon disease. METHODS: Matched in vivo synovial oxygen measurements (invasive and encapsulating tenosynovium and joint synovium) were taken intraoperatively using a microelectrode technique in patients having elective hand surgery for RA. Patients having elective hand surgery for indications other than inflammatory synovitis were recruited as controls. In parallel, RA synovial tissue was harvested and stained for vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-2alpha. Tissue was also cultured under either hypoxic (1% O(2)) or normoxic (21% O(2)) conditions to investigate the effect of hypoxia on the expression of VEGF and its soluble receptor, as well as on the key cytokines interleukin (IL)-6, IL-8, IL-10 and the chemokine monocyte chemoattractant protein-1. RESULTS: Invasive tenosynovium was observed to be significantly more hypoxic than either noninvasive tenosynovium or joint synovium in the same patients. Furthermore, RA tenosynovium was shown to be more hypoxic than tenosynovium in patients without RA. This hypoxia was accompanied by expression of VEGF and hypoxia-inducible factor-2alpha. Using in vitro joint synovial cell cultures, upregulation of VEGF expression was shown to be a consequence of this in vivo hypoxia. Furthermore, hypoxia downregulated release of monocyte chemoattractant protein-1 and the immunoregulatory cytokine IL-10. CONCLUSIONS: These data demonstrate that hypoxia is a feature of rheumatoid tendon disease and differentially regulates angiogenesis and the inflammatory cascade in RA