Formation of the trochlear nerve within the anterior hindbrain provides a model system to study a simple axonal projection within the vertebrate central nervous system. We show that trochlear motor neurons are born within the isthmic organiser and also immediately posterior to it in anterior rhombomere 1. Axons of the most anterior cells follow a dorsal projection, which circumnavigates the isthmus, while those of more posterior trochlear neurons project anterodorsally to enter the isthmus. Once within the isthmus, axons form large fascicles that extend to a dorsal exit point. We investigated the possibility that the projection of trochlear axons towards the isthmus and their subsequent growth within that tissue might depend upon chemoattraction. We demonstrate that both isthmic tissue and Fgf8 protein are attractants for trochlear axons in vitro, while ectopic Fgf8 causes turning of these axons away from their normal routes in vivo. Both inhibition of FGF receptor activation and inhibition of Fgf8 function in vitro affect formation of the trochlear projection within explants in a manner consistent with a guidance function of Fgf8 during trochlear axon navigation.

The management of glenoid bone loss is a major challenge in both complex primary and revision arthroplasty surgery. To deal with this problem, a number of techniques have been advocated, although there has been no previous systematic review of the literature. In the present review, we have attempted to identify a coherent strategy for addressing this problem, taking into account the degree of bone loss, the advantages and limits of standard implants, bone reconstruction techniques and the use of customized prostheses.

Low-grade central osteosarcoma (LGCO) is a rare variant of osteosarcoma which is difficult to diagnose. If not treated appropriately, the tumour can recur with higher-grade disease. We reviewed our experience of this condition to try and identify factors that could improve both diagnosis and outcome. 18 patients out of 1540 osteosarcoma cases (over 25 years) had LGCO (1.2%). Only 11 patients (61%) were direct primary referrals. Almost 40% (7 of 18) cases were referred after treatment elsewhere when the diagnosis had not been made initially and all presented with local recurrence. Of the 11 who presented primarily, the first biopsy was diagnostic in only 6 (55%) cases. Of the remaining cases, up to three separate biopsies were required before a definitive diagnosis was made. Overall survivorship at 5 years was 90%. 17 patients were treated with limb salvage procedures, and one patient had an amputation. The diagnosis of LGCO remains challenging due to the relatively nonspecific radiological and histological findings. Since treatment of LGCO is so different to a benign lesion, accurate diagnosis is essential. Any difficult or nondiagnostic biopsies of solitary bone lesions should be referred to specialist tumour units for a second opinion.

No abstract