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.

Quilting of full thickness grafts in the hand.

A skin graft is the simplest way to reconstruct an area of skin loss. To improve the chance of successful take, shearing forces and haematoma formation between the bed and the graft must be reduced. To achieve this, many surgeons use a tie-over dressing to secure the graft. However, 'quilting' the graft to the wound bed is an alternative method for securing grafts which may be superior to tie-over dressings. The purpose of this study was to compare the outcome of securing a full thickness graft by tie-over dressing versus quilting in the hand. To do this, we performed a retrospective review of graft-take in a consecutive series of 40 patients undergoing dermofasciectomy for Dupuytren's disease over a five year period. Our results demonstrate no significant difference in graft-take comparing grafts secured with a tie-over dressing or by quilting. Importantly, there were no cases of injury to the tendons or neurovascular structures in those cases where the graft was secured by quilting. Our technique for securing the graft by quilting is less time-consuming compared with a tie-over dressing. Therefore, we no longer use tie-over dressings to secure full-thickness grafts in the hand.

Hypoxia upregulates angiogenesis and synovial cell migration in rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is characterised by invasion of cartilage, bone and tendon by inflamed synovium. Previous studies in our laboratory have shown that hypoxia is a feature of RA synovitis. In the present study, we investigated the consequences of hypoxia on angiogenesis and synovial fibroblast migration in RA. METHODS: Synovial tissue was harvested from RA patients, and synovial membrane cells were cultured under conditions either of hypoxia (1% oxygen) or normoxia (21% oxygen). Protein levels of matrix metalloproteinases (MMPs) and angiogenic factors were measured, while RNA was extracted for PCR quantification of MMPs/tissue inhibitors of MMP (TIMPs) and angiogenic factors. Migration of RA synovial fibroblasts through collagen, and the effect of RA synovial cell supernatants in an in vitro angiogenesis assay, were utilised to determine the functional relevance of changes in mRNA/protein. RESULTS: We observed upregulation under hypoxic conditions of MMPs responsible for collagen breakdown, specifically collagenase MMP-8, and the gelatinases MMP-2 and MMP-9, at both mRNA and protein levels. Increased MT1-MMP mRNA was also observed, but no effect on TIMP-1 or TIMP-2 was detected. RA fibroblast migration across collagen was significantly increased under hypoxic conditions, and was dependent on MMP activity. Furthermore, expression of angiogenic stimuli, such as vascular endothelial growth factor (VEGF), and VEGF/placental growth factor heterodimer, was also increased. Crucially, we show for the first time that hypoxia increased the angiogenic drive of RA cells, as demonstrated by enhanced blood vessel formation in an in vitro angiogenesis assay. CONCLUSIONS: Hypoxia may be responsible for rendering RA synovial lining proangiogenic and proinvasive, thus leading to the debilitating features characteristic of RA.

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.

Chest wall reconstruction using a turbocharged chimaeric anterolateral thigh flap.

Extremely large chest wall defects may result following salvage oncological surgery. Typically these defects involve a large skin defect combined with a variable resected area of underlying muscle and ribs. In situations where the skin defect is very large the use of a large latissimus dorsi flap may require skin grafting to the donor site if a myocutaneous flap is used or to the recipient defect if a muscle-only flap is used. Alternatively a transverse rectus abdominis flap is a second option but in certain cases this may not be available. We describe the use of a free anterolateral thigh flap to reconstruct a chest wall defect and demonstrate the principle of side-to-side stacking of separate skin paddles to achieve skin closure of a massive defect whilst permitting primary closure of the donor site. The principle of turbocharging components of a chimaeric flap is also described.

Attitudes to blood transfusion post arthroplasty surgery in the United Kingdom: a national survey.

Five hundred orthopaedic surgeons and 336 anaesthetists were surveyed to assess current UK attitudes towards transfusion practice following arthroplasty surgery. Seventy-two percent of surgeons and 73% of anaesthetists responded to the survey. In an uncomplicated patient following total hip arthroplasty, 53.2% of surgeons and 63.1% of anaesthetists would transfuse at or below a haemoglobin (Hb) level of 8 g/dL. Surgeons tended to be more aggressive in their attitudes, with a mean transfusion threshold of 8.3 g/dL compared to 7.9 g/dL for anaesthetists (p<0.01), and with 97% of surgeons transfusing two or more units compared to 78% of anaesthetists (p<0.01). This threshold Hb increased if the patient was symptomatic (surgeons 9.3 g/dL, anaesthetists 8.8 g/dL, p<0.05) or was known to have pre-existing ischaemic heart disease (surgeons 9.0 g/dL, anaesthetists 9.2 g/dL, p<0.05). A wide variability in attitudes and practices is demonstrated, and the development and adoption of consensus guidelines needs to be encouraged if efforts to reduce the use of blood products are to succeed.