Multivalent Fcγ-receptor engagement by a hexameric Fc-fusion protein triggers Fcγ-receptor internalisation and modulation of Fcγ-receptor functions.

Engagement of Fcγ-receptors triggers a range of downstream signalling events resulting in a diverse array of immune functions. As a result, blockade of Fc-mediated function is an important strategy for the control of several autoimmune and inflammatory conditions. We have generated a hexameric-Fc fusion protein (hexameric-Fc) and tested the consequences of multi-valent Fcγ-receptor engagement in in vitro and in vivo systems. In vitro engagement of hexameric-Fc with FcγRs showed complex binding interactions that altered with receptor density and triggered the internalisation and degradation of Fcγ-receptors. This caused a disruption of Fc-binding and phagocytosis. In vivo, in a mouse ITP model we observed a short half-life of hexameric-Fc but were nevertheless able to observe inhibition of platelet phagocytosis several days after hexameric-Fc dosing. In cynomolgus monkeys, we again observed a short half-life, but were able to demonstrate effective FcγR blockade. These findings demonstrate the ability of multi-valent Fc-based therapeutics to interfere with FcγR function and a potential mechanism through which they could have a sustained effect; the internalisation and degradation of FcγRs.

Internal fixation of scaphoid non-union: a comparative study of three methods.

In this study we compared the results of three methods of fixation for scaphoid non-union. The implants used were the AO 2 mm mini-fragment screw, the Herbert screw and the Kirschner (K) wires. Between 1990 and 1999, 132 patients underwent surgery for scaphoid fractures. We used the modified Filan and Herbert classification. Patients with acute fractures and patients requiring vascularised bone grafts were excluded. Twenty-six non-unions were fixed with an AO mini-fragment screw, 58 with a Herbert screw, and nine with K-wires. Radiological union was achieved in 85% of cases using the AO screw, 77% using the Herbert screw and 55% using the K-wire fixation. Statistically there was no significant difference between the AO and Herbert screw groups in terms of rate and speed of radiological union. The mechanical strength of the implant and the compression achieved did not seem to influence the union rate and speed. The type of bone graft (iliac crest or distal radius) did not significantly affect the union rates. Finally, K-wire fixation, either as a primary method or as a salvage procedure, produced inferior results and required prolonged immobilisation in plaster.

Functional outcome of high-pressure injection injuries of the hand.

BACKGROUND: High-pressure injection (HPI) injury of the hand is a serious injury that can be potentially devastating. There have been a number of publications on the results of its treatment, but we are not aware of a report on the functional outcome of these hands. METHODS: We assessed the functional outcome of 15 patients with HPI injuries. All patients were treated operatively, with a mean delay of 11.7 hours. The patients were examined by a doctor and an occupational therapist using a work simulator. RESULTS: Our study revealed a significant reduction of static and dynamic muscle testing parameters compared with the uninjured hand. Six patients lost a digit and four patients had to change their occupation after the injury. CONCLUSION: Deterioration of hand function is a predictable outcome of HPI injury. This information should be shared with the patient at the outset so as to avoid subsequent disappointment.

Clinical diagnosis of triquetrolunate ligament injuries.

The clinical diagnosis of peritriquetral injuries is difficult. We describe our diagnostic technique based on specific questions and three clinical tests. The accuracy of our diagnostic technique was compared prospectively with the definitive diagnosis made at arthroscopy. Preoperatively, 19 patients were diagnosed as having triquetrolunate dissociation. This was confirmed at arthroscopy in 17. Another five patients not diagnosed preoperatively were also diagnosed at arthroscopy as having mainly triquetrolunate dissociation. The sensitivity of our diagnostic protocol was 0.77 and the positive predictive value was 0.89.

Neglected rupture of the patellar tendon.

Neglected rupture of the patellar tendon is a rare but well recognised complication of knee trauma. We present the case of a 43-year-old man who sustained a complete rupture of the patellar tendon of his left knee following a fall. Clinical diagnosis was delayed by 2 months and was confirmed by magnetic resonance imaging. Treatment began with skeletal patellar traction and was followed by late reconstruction of the patellar tendon and transfer of the gracilis and semitendonosus tendons supplemented by figure-of-eight tension band wiring.

Open and closed arthrodesis of the rheumatoid wrist using a modified (Stanley) Steinmann pin.

In a series of 21 patients (22 wrists) with rheumatoid arthritis, arthrodesis of the wrist was done using a modified Steinmann pin (Stanley) either by an open or closed technique. The open technique, which included fragmenting the carpal bones (12 cases), was mainly used when additional procedures were needed simultaneously. The closed technique simply required insertion of the Stanley pin under fluoroscan control through a small incision over the metacarpal head. Nine out of 12 wrists treated with the open technique and nine out of ten of those treated by the closed technique were successfully fused. Complications were few. A single patient was dissatisfied due to continuing pain. Two out of the four pins that migrated (both involving the open technique) have been removed.

Proximal row transcarpal fracture from a punching injury.

We describe an unusual case of a 31-year-old woman who injured the right dominant wrist when she punched an assailant's shoulder. She described a mechanism of direct compression, with the wrist in hyperextension, radial deviation and the forearm in pronation. She sustained an oblique transverse fracture of the proximal pole of the scaphoid and a coronal plane fracture of the lunate and the triquetrum. This unusual proximal row transcarpal fracture is in conflict with the Mayfield sequence and was caused by a low velocity injury.

The effect of ongoing litigation on outcome scores following open reduction and internal fixation of the calcaneum.

All sixteen patients who had undergone open reduction and internal fixation (ORIF) of the calcaneum by the senior author between April 1993 and August 1996 were included in the study. Two had died from unrelated illnesses and one had failed to attend any follow-up following discharge. The remaining 13 were reviewed by the main author. As part of a complete clinical, radiological and functional assessment, Buckley and Meek (B&M) and Kerr and Atkins (K&A) outcome scores were calculated as well as a satisfaction score obtained by a visual analogue scale (VAS). Statistical analysis of the results using Wilcoxen's paired and unpaired ranking scores showed that the initial grade of the fracture, degree of operative reduction, correction of width of the heel and post-operative ranges of motion had no significant correlation to either B&M or K&A outcome scores or to the VAS score. However, the presence of ongoing litigation was significantly correlated to the scores (VAS < 0.01, B&M < 0.05, K&A < 0.05). These findings cast doubt on the validity of post operative scoring for fracture of the calcaneum in the presence of ongoing litigation.