Blond McIndoe Research Foundation

Laxity in the trapeziometacarpal (TMC) joint is a debilitating condition usually affecting a young population. It can be treated operatively with ligament reconstruction. The purpose of this study was to determine the effectiveness of the Arthrex Mini TightRope® in reinforcing the stabilizing ligaments in an unstable TMC joint without decreasing the range of motion of the thumb. This method was compared with the "gold standard" published by Eaton and Littler in 1973. Six fresh frozen arms from five cadavers were included. TMC joint laxity was measured on stress view radiographs as the ratio of the radial subluxation(RS) of the first metacarpal in relation to the trapezium, by the first metacarpal articular width(AW) (as described by Wolf in 2009). Measurements of the pre- and post-operative range of motion (ROM) were performed and compared. Both the Arthrex Mini TightRope® and the Eaton-Littler stabilization improved the stability of the TMC joint. The pre-operative laxity value (ratio RS/AW) of 0.27 was significantly (P = 0.02) improved by each of the surgical interventions (Eaton-Littler RS/AW = 0.05 and Tightrope RS/AW = 0.09). The pre- and post-operative range of motion was not significantly different by each of the surgical interventions. There were no significant differences between the two stabilizing methods regarding laxity or range of motion. The Arthrex Mini TightRope® provided a good stabilization method for the TMC joint in this anatomical model without compromising the range of motion.

Wound repair is a quiescent mechanism to restore barriers in multicellular organisms upon injury. In chronic wounds, however, this program prematurely stalls. It is known that patterns of extracellular signals within the wound fluid are crucial to healing. Extracellular pH (pHe) is precisely regulated and potentially important in signaling within wounds due to its diverse cellular effects. Additionally, sufficient oxygenation is a prerequisite for cell proliferation and protein synthesis during tissue repair. It was, however, impossible to study these parameters in vivo due to the lack of imaging tools. Here, we present luminescent biocompatible sensor foils for dual imaging of pHe and oxygenation in vivo. To visualize pHe and oxygen, we used time-domain dual lifetime referencing (tdDLR) and luminescence lifetime imaging (LLI), respectively. With these dual sensors, we discovered centripetally increasing pHe-gradients on human chronic wound surfaces. In a therapeutic approach, we identify pHe-gradients as pivotal governors of cell proliferation and migration, and show that these pHe-gradients disrupt epidermal barrier repair, thus wound closure. Parallel oxygen imaging also revealed marked hypoxia, albeit with no correlating oxygen partial pressure (pO2)-gradient. This highlights the distinct role of pHe-gradients in perturbed healing. We also found that pHe-gradients on chronic wounds of humans are predominantly generated via centrifugally increasing pHe-regulatory Na+/H+-exchanger-1 (NHE1)-expression. We show that the modification of pHe on chronic wound surfaces poses a promising strategy to improve healing. The study has broad implications for cell science where spatial pHe-variations play key roles, e.g. in tumor growth. Furthermore, the novel dual sensors presented herein can be used to visualize pHe and oxygenation in various biomedical fields.

Over recent years we have been studying the possibility of targeting radiolabelled monoclonal antibodies to human brain tumours in vivo. This work began with the development of panels of monoclonal antibodies for use in the diagnosis of brain tumour biopsies and cerebrospinal fluid infiltrates (1). Certain of these antibodies were then chosen for use in vivo, labelled with I–131.