Blood metal ions have been widely used to investigate metal-on-metal hip replacements, but their ability to discriminate between well-functioning and failed hips is not known. The Medicines and Healthcare products Regulatory Agency (MHRA) has suggested a cut-off level of 7 parts per billion (ppb). We performed a pair-matched, case-control study to investigate the sensitivity and specificity of blood metal ion levels for diagnosing failure in 176 patients with a unilateral metal-on-metal hip replacement. We recruited 88 cases with a pre-revision, unexplained failed hip and an equal number of matching controls with a well-functioning hip. We investigated the 7 ppb cut-off level for the maximum of cobalt or chromium and determined optimal mathematical cut-off levels from receiver-operating characteristic curves. The 7 ppb cut-off level for the maximum of cobalt or chromium had a specificity of 89% and sensitivity 52% for detecting a pre-operative unexplained failed metal on metal hip replacement. The optimal cut-off level for the maximum of cobalt or chromium was 4.97 ppb and had sensitivity 63% and specificity 86%. Blood metal ions had good discriminant ability to separate failed from well-functioning hip replacements. The MHRA cut-off level of 7 ppb provides a specific test but has poor sensitivity.

We carried out metal artefact-reduction MRI, three-dimensional CT measurement of the position of the component and inductively-coupled plasma mass spectrometry analysis of cobalt and chromium levels in whole blood on 26 patients with unexplained pain following metal-on-metal resurfacing arthroplasty. MRI showed periprosthetic lesions around 16 hips, with 14 collections of fluid and two soft-tissue masses. The lesions were seen in both men and women and in symptomatic and asymptomatic hips. Using three-dimensional CT, the median inclination of the acetabular component was found to be 55 degrees and its positioning was outside the Lewinnek safe zone in 13 of 16 cases. Using inductively-coupled plasma mass spectrometry, the levels of blood metal ions tended to be higher in painful compared with well-functioning metal-on-metal hips. These three clinically useful investigations can help to determine the cause of failure of the implant, predict the need for future revision and aid the choice of revision prostheses.

Summary.  Beriplex, a prothrombin complex concentrate (PCC), was administered to 42 patients requiring immediate reversal of their oral anticoagulant therapy. The dose administered was determined using the pretreatment International Normalized Ratio (INR). Blood samples were obtained before treatment and at 20, 60 and 120 min after treatment. The following investigations were performed on all samples – INR, clotting factors II, VII, IX and X, coagulation inhibitors protein C (PC) and antithrombin (AT), and other markers of disseminated intravascular coagulation, plasma fibrinogen, d‐dimer and platelet count. Immediate reversal of the INR, the vitamin K‐dependent clotting factors and PC was achieved in virtually all patients. Reduced AT levels were present in 18 patients before treatment. Further slight AT reductions occurred in four patients, but other associated abnormalities of haemostasis were observed in only one of the four patients. One patient with severe peripheral vascular disease, sepsis and renal and cardiac failure died of a thrombotic stroke following leg amputation, 48 h after receiving Beriplex. No other arterial and no venous thromboembolic events occurred within 7 d of treatment. Beriplex is effective in rapidly reversing the anticoagulant effects of warfarin, including PC deficiency, without inducing coagulation activation. Caution should continue to be exercised in the use of these products in patients with disseminated intravascular coagulation, sepsis or liver disease.

Metalloenzymes have an important role in repair and regenerative processes in skin wounds. Demands for different enzymes vary according to the phase in the healing cascade and constituent events. Sequential changes in the concentrations of calcium, copper, magnesium and zinc were studied in the incisional wound model in the rat over a 10 d period. Copper levels remained low ( 10 µg\g dry weight) throughout, but calcium, magnesium and zinc increased from wounding and peaked at about 5 d at a time of high inflammation, granulation tissue formation and epidermal cell proliferation. Metal concentrations declined to normal by 7 d when inflammation had regressed, re-epithelialisation of the wound site was complete and the ' normalisation ' phase had commenced. Although the wound was overtly healed by 10 d, the epidermis was still moderately hyperplastic. In view of competitive binding of trace metals at membrane receptors and carrier proteins, the ratios or balance between these trace metals was examined and the significance is discussed. Using immunocytochemistry, we demonstrated increases in metallothionein immunoreactivity as an indication of zinc and copper activity in the papillary dermis and in basal epidermal cells near the wound margin 1-5 d after wounding. This is consistent with metalloenzyme requirements in inflammation and fibrogenesis. Calmodulin, a major cytosolic calcium binding protein was highest in maturing keratinocytes and in sebaceous gland cells of normal skin ; it was notably more abundant in the epidermis near the wound margin and in re-epithelialising areas at a time when local calcium levels were highest.Key words : Skin wounds ; repair ; trace metalloenzymes ; metal ion balance ; zinc ; calcium ; copper ; magnesium. Wound healing in the skin and in other tissues of the human body depends upon the availability of competent cells to carry out repair processes, appropriate activation by hormones, growth factors, cytokines and chemotactic factors, and a microenvironment favouring cell movement, proliferation and functional maturation (Grotendorst, 1992 ;Hunt & Hussain, 1992). Metal ions and metalloenzymes feature prominently in this wound healing environment and experimental and clinical studies are available to show that deficiencies in zinc, copper, calcium, iron or magnesium are potential causes of abnormal homeostatic mechanisms and impaired wound healing (Moynahan, 1974 ;Lansdown, 1995) tention recently has focused upon the role of metalloproteinases in the degradation of extracellular matrix in the early phases of wound healing (Nwomeh et al. 1998), it is to be expected that the demands for these and other metalloenzymes will vary greatly as the profile of wound healing proceeds. Surprisingly, the action and interaction of trace metals in the skin under normal conditions is not well documented, and sequential changes in the healing wound are not published for any species (Lansdown, 1995).Much of the trace metal requirement for the body is derived from the diet, but many...