Thalidomide and neurotrophism.

BACKGROUND: Following the thalidomide disaster (1958-62), Henkel and Willert analysed the pattern of dysmelia in the long bones (J Bone Joint Surg Br. 51:399-414, 1969) and the extremities, Willert and Henkel (Z Orthop Ihre Grenzgeb. 107:663-75, 1970). Willert's material from deformed extremities is re-examined here asking "How does thalidomide reduce the skeleton?" MATERIALS AND METHODS: We reviewed the original data collection of Willert and Henkel (Z Orthop Ihre Grenzgeb. 107:663-75, 1970), comprising musculoskeletal histology slides from 30 children affected by thalidomide with radiographs of hands (19 cases) and feet (4 cases). RESULTS: All original observations by Willert and Henkel (Z Orthop Ihre Grenzgeb. 107:663-75, 1970), were verified. Radial rays of the hand disappeared early, but the foot was spared until late. Radiology confirms that bone reduction in the hand (aplasia or hypoplasia in the thumb and index finger) coincides with sensory segmental nerve C6. In the foot, reduction of the toes is rare, but mesenchymal excess (polydactyly) occurs in the hallux (L5 sclerotome), usually associated with absent tibia (L4 sclerotome). Histology confirms skeletal mesenchymal components to be unremarkable, contrasting with grossly abnormal bony architecture, a striking discordance between microscopic and macroscopic findings. No necrosis or vascular pathology was seen. CONCLUSION: The basic lesion was an abnormal quantity rather than quality of mesenchyme. Cell populations result from cellular proliferation, controlled in early limb bud formation by neurotrophism. Thalidomide is a known sensory neurotoxin in adults. In the embryo, sensorineural injury alters neurotrophism, causing increased or diminished cell proliferation in undifferentiated mesenchyme. Differentiation into normal cartilage occurs later, but within an altered mesenchymal mass. Reduction or excess deformity results, with normal histology, a significant finding. The primary pathological condition is not in the skeleton, but in the nerves.

Metallic debris from metal-on-metal total hip arthroplasty regulates periprosthetic tissues.

The era of metal-on-metal (MoM) total hip arthroplasty has left the orthopaedic community with valuable insights and lessons on periprosthetic tissue reactions to metallic debris. Various terms have been used to describe the tissue reactions. Sometimes the nomenclature can be confusing. We present a review of the concepts introduced by Willert and Semlitsch in 1977, along with further developments made in the understanding of periprosthetic tissue reactions to metallic debris. We propose that periprosthetic tissue reactions be thought of as (1) gross (metallosis, necrosis, cyst formation and pseudotumour); (2) histological (macrophage-dominated, lymphocyte-dominated or mixed); and (3) molecular (expression of inflammatory mediators and cytokines such as interleukin-6 and tumor necrosis factor-alpha). Taper corrosion and modularity are discussed, along with future research directions to elucidate the antigen-presenting pathways and material-specific biomarkers which may allow early detection and intervention in a patient with adverse periprosthetic tissue reactions to metal wear debris.

Five- to 10-year results using a noncemented modular revision stem without bone grafting.

The aim of the study was to evaluate the 5- to 10-year results (mean, 6.2 years) of a modular uncemented revision stem (Profemur-R). From a total series of 184 consecutive stem revisions, the first 73 were evaluated. The implant was fixed without bone grafting in all cases. The average Harris hip score increased from 40 to 75. A complete remodeling of bone defects could be documented radiographically in 70% of the cases and a partial restoration in 30%. Progressive subsidence appeared in 2 stems. Three rerevisions were required, including 1 septic case. The survival rate with aseptic loosening as the end point was 96% over an average of 10 years. The revision prosthesis examined in this study can be considered a viable and useful option to reconstruct femoral defects in revision hip arthroplasty.

Metal-on-metal bearings and hypersensitivity in patients with artificial hip joints. A clinical and histomorphological study.

BACKGROUND: Some patients who have a total hip replacement with a second-generation metal-on-metal articulation have persistent or early recurrence of preoperative symptoms. Characteristic histological changes in the periprosthetic tissues suggested the development of an immunological response. Therefore, in order to determine the relevance of these symptoms, we performed a study of the clinical data and periprosthetic tissues associated with endoprostheses with a metal-on metal articulation that had been retrieved at revision. METHODS: Periprosthetic tissues as well as the clinical data on the patients were obtained from the first nineteen consecutive revisions performed at the treating hospitals. At the time of the revision, fourteen patients had the metal-on-metal articulation exchanged for either an alumina-ceramic or a metal-on-polyethylene articulation. Five patients received another second-generation metal-on-metal total joint replacement. Five-micrometer sections were prepared from the tissue samples, were stained with routine and immunohistochemical methods, and were examined histologically. Histological specimens from three groups of patients, two of which were treated with non-metal-on-metal implants, served as controls. RESULTS: The majority of patients had persistence of their preoperative pain or early recurrence of the pain after the original total hip replacement, and often a pronounced hip joint effusion had developed after the original replacement. Radiographic follow-up showed the development of radiolucent lines in five hips and of osteolysis in another seven hips. At the revision surgery, both the cup and the stem were found to be well fixed in nine patients. The characteristic histological features were diffuse and perivascular infiltrates of T and B lymphocytes and plasma cells, high endothelial venules, massive fibrin exudation, accumulation of macrophages with droplike inclusions, and infiltrates of eosinophilic granulocytes and necrosis. Only a few metal particles were detected. Immunohistochemical analysis demonstrated that the cellular reaction was still active. The patients who received another second-generation metal-on-metal articulation at the time of the revision had no decrease in symptoms. In the control group of tissues obtained at revisions of endoprostheses without cobalt, chromium, or nickel articulations, there were no similar signs of immune reactions. CONCLUSIONS: These histological findings support the possibility of a lymphocyte-dominated immunological response. Although the prevalence of this reaction is low, the persistence or early reappearance of symptoms, including a marked joint effusion and the development of osteolysis, after primary implantation may suggest the possibility of such a reaction.