Spondyloepiphyseal dysplasia tarda: description of one case.

The authors describe the case of an Italian male aged 19 years who came to their observation for severe limping with reduction in hip movement and spondyloepiphyseal radiographic modifications of an osteochondrodysplastic origin. The studies carried out led to a diagnosis of spondyloepiphyseal dysplasia tarda (SEDT).

Morphometric and microanalytical analyses of alumina wear particles in hip prostheses.

We analysed tissues harvested during 24 retrievals of hip joint prostheses, with one or both articular components made of alumina. We describe the morphology of wear particles, measure their size and analyse their chemical composition. We relate histopathological aspects to the parameters that characterize ceramic wear particles, and notice that tissue reaction relates to the physical aspect and amount of wear debris and does not necessarily depend on their chemical composition.

Toxicity of cyanoacrylates in vitro using extract dilution assay on cell cultures.

Comparative cytotoxicity testing of four cyanoacrylate adhesives suggested for orthopaedic applications was performed. These substances were placed in complete culture medium with serum and the resulting extraction fluids were tested on L 929 cells and human lymphocytes. Testing procedures include cell morphology assessment using light microscopy and vital dyes, cell counting using a computer-assisted image analysis system, cell growth measurement using total protein content assay and cell viability assessment using the MTT method. Quantitation of the toxicity of the degradation products released by cyanoacrylates in the extracts was achieved and differences in the cytopathic effect related to the chemical composition of the cyanoacrylates were found. A toxicity rating of the assayed cyanoacrylate adhesives was obtained as follows (in order of increasing toxicity): BCA < xCA < ECAg < ECAl.

Expression of the CD69 activation antigen on lymphocytes of patients with hip prosthesis.

The aim of the study was to evaluate the sensitization to metals in patients with Co-Cr hip prosthesis. Peripheral blood mononuclear cells (PBMC) were collected from 14 healthy donors and three groups of patients: 10 candidates for primary total joint replacements, 11 patients with well-fixed implant and 13 patients with aseptic loosening of the hip prosthesis. PBMCs were cultured with the metal ions employed for implant manufacturing and the expression of CD69 activation antigen on CD3/T lymphocytes was detected by flow cytometry. Chromium extract increased significantly the expression of CD3/CD69 phenotype in patients with loosening of hip prosthesis. The chromium-induced 'activation index' was higher in patients with loosening of hip prosthesis than in healthy donors and in pre-implant patients. The cobalt-stimulated PBMC of patients with either well-fixed or loosened prosthesis had an 'activation index' significantly higher than healthy donors. The activation index values were used to graduate the PBMC-response as 'normal' (> or = 0.9 and < 2), 'low' (< 0.9) and 'high' (> or = 2): an high-activation index was observed only in chromium-exposed PBMC of patients with prosthesis. Our data show that chromium released from orthopedic implants could be responsible for the lymphocyte sensitization and flow cytometry is an easy and reliable method for monitoring the hypersensitivity state in patients with metal prostheses. Activated lymphocytes in the peri-implant tissue are likely to elicit a localized immune response and contribute to maintain the inflammatory process evolving in the implant failure.

Microradiographic and histochemical evaluation of mineralization inhibition at the bone-alumina interface.

Microradiographic and histochemical tests were used to examine the behaviour of the bone tissue close to the alumina coating in cementless hip prostheses which were radiologically stable and explanted because of pain. The presence was detected of a decalcification stripe of the bone tissue with a thickness of about 300 microns, parallel to the prosthesis profile and in appearance not influenced by the roughness of the surface. This phenomenon was attributed to the presence of aluminium ions similarly to what happens in osteomalacic osteodystrophy in nephropathic dialysed patients. It was concluded that the phenomenon must be carefully considered because, in the long term, it could cause failure in the alumina coating.

Cytotoxicity testing of cyanoacrylates using direct contact assay on cell cultures.

The use of a tissue adhesive for surgical procedures has prompted a large number of clinical and experimental studies. Alkyl-2-cyanoacrylate esters constitute a family of adhesives with good mechanical properties but their biological compatibility has to be assessed. In this study the cytotoxicity of three commercially available cyanoacrylates and one of unknown composition has been determined. The first part of the study deals with direct contact testing procedures using L 929 cells challenged with drops of adhesives: cell morphology, cell growth and bacterial growth inhibition were assayed. Testing methods included cell viability assay using vital dyes, cell growth measurement using crystal violet staining uptake and bacterial growth assay using S. aureus growth inhibition. All the cyanoacrylate adhesives tested were found to be cytotoxic and to inhibit cell proliferation: differences between the cyanoacrylates were found.

Apoptosis in peri-implant tissue.

The authors examined 54 biopsies taken from the tissue surrounding loosened hip joint prostheses. In situ apoptotic cell identification was performed by the detection of single- and double-stranded DNA breaks that occurred in the early stages of apoptosis. Both types of breaks can be revealed by labeling the free 3'-OH termini with modified nucleotides (fluoresceine-dUTP) in an enzymatic reaction catalyzed by terminal deoxynucleotidyl transferase (TdT). Results were correlated with the presence of wear debris in the tissue and with the use of bone cement for prosthesis fixation. Apoptotic cells were present in a higher percentage in tissue sections where metal particles were present (24% apoptotic cells) if compared to areas where no wear (6%), or plastic wear (2.8%) or ceramic wear (1.5%) was observed. Apoptosis is neither related to bone cement, nor to the time it takes for the implant to fail. Cell death by apoptosis may be important in implants which release metal ions by corrosion or wear and may have been underestimated up to now, as it is a 'clean' way of cell death, leading to limited damage in the surrounding tissues.

Nitric oxide synthase in tissues around failed hip prostheses.

Nineteen patients who had undergone hip revision surgery for aseptic loosening of joint prostheses were studied. Tissue samples were harvested at the interface between bone and implant, either at the stem or at the cotyle level. Immunohistochemistry was performed on tissue sections to detect nitric oxide synthase (NOS), the enzyme which enables the synthesis of nitric oxide (NO), a molecule which can activate bone resorption. Quantitative analysis of the positive cells and correlation with the presence of particulate wear debris and radiological data were performed. The authors observed a trend towards a moderate increase in positive cells due to inducible NOS in tissues containing particulate wear debris, especially of a plastic material. This increase, however, did not achieve statistical significance. On the contrary, there was a statistical correlation between iNOS (inducible NOS) and the severity of osteolysis around the prosthetic implant. Pharmacological control of the biosynthesis of NO may be considered in the prevention or treatment of loosening.

Cytokine release in mononuclear cells of patients with Co-Cr hip prosthesis.

The aim of this study was the evaluation of the release of bone-resorbing cytokines in peripheral blood mononuclear cells (PBMC) of patients with aseptic loosening of Co-Cr hip prostheses. TNF-alpha, IL-6, and GM-CSF were measured in both unstimulated and PHA-stimulated PBMC, and in PBMC cultured in the presence of chromium and cobalt extracts. Blood samples from healthy donors were used as controls. Serum samples of both patients and healthy donors were tested to determine the concentration of metal ions. The proportion of lymphocyte, monocyte and lympocyte subpopulation in cultured PBMC did not differ in patients and the control group. In unstimulated PBMC the release of TNF was significantly higher in patients than in the control group, while IL-6 was significantly decreased and no change was observed for GM-CSF. When the PBMC were challenged with chromium extract, all the 'index of cytokine release' resulted higher in patients than in the control group; cobalt extract increased both the TNF and GM-CSF index, but not the index of IL-6 release. Metal concentrations in serum from patients were significantly increased and correlated with the TNF release in PBMC stimulated with both metal extract. Our results suggest that a CoCr-implant releases a large amount of metal ions which could mediate the priming or the renewal of a cell-mediated hypersensitivity reaction. The prevalence of circulating lymphocytes responsible for the delayed hypersensitivity, namely Thl, would justify both the significant increase of TNF and the significant decrease of IL6 in unstimulated PBMC of patients, as well as the significant increase of the 'index of cytokine release' after the challenge with metal ions.

Giant-cell tumor of bone.

Of 327 patients who had a giant-cell tumor of bone and were seen at the Istituto Rizzoli, 293 were treated at the Institute, and 280 of these were followed for two to forty-four years. The distribution according to sex and age of the patient and site of the tumor was similar to the distributions in major reports of large series. The tumor usually involved the metaphysis and the epiphysis, but was occasionally limited to the metaphysis, and in only 2 per cent of the patients was it adjacent to an open growth plate. The tumor on occasion invaded the articular space, also involving the ligaments and the synovial membrane. Extension to an adjacent bone through the joint occurred in 5 per cent of the tumors. Our radiographic grading, which is roughly comparable with the staging system of Enneking et al., was Grade I in 4 per cent, II in 74 per cent, and III in 22 per cent of 266 patients before treatment. A pathological fracture was apparent on the first radiograph in 9 per cent of the patients. In the 280 patients with adequate follow-up, 331 surgical procedures were performed. The rate of local recurrence was 27 per cent in the 151 intralesional procedures, 8 per cent in the 122 marginal excisions, and zero in the fifty-eight wide or radical procedures. These results did not correlate with the radiographic grade of the lesion. Of the fifty-one local recurrences that were seen after treatment at our institution, 90 per cent appeared in the first three years after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Benign fibrous histiocytoma of bone.

The cases of seven patients who had a lytic lesion that was histologically similar to a metaphyseal fibrous defect (non-ossifying fibroma) of bone were studied. The patients all were adults and had pain without a fracture. These features were considered distinctive for the lesion, which has the same histological appearance as benign fibrous histiocytoma of soft tissue. The lesion is a benign tumor with fibroblastic and histiocytic differentiation. This picture may be seen in foci in other lesions of bone (aneurysmal bone cyst, fibrous dysplasia, and giant-cell tumor). Ten cases of giant-cell tumor of bone that had a large component of the same foci were also reviewed. It should be emphasized that these areas are secondary reactive tissue rather than the true neoplastic tissue of benign fibrous histiocytoma.

Bone-resorbing cytokines in serum of patients with aseptic loosening of hip prostheses.

Our aim was to determine if the serum levels of bone-resorbing cytokines (IL-1beta, TNF-alpha, IL-6, GM-CSF) are altered in patients with aseptic loosening of a total hip prosthesis, and if such levels are influenced by the type of implant. We determined cytokine levels in sera from 35 patients before revision for failed total hip arthroplasty and compared them with those in 25 healthy donors. We also assessed the soluble receptor of interleukin-2 (sIL-2r) in serum as an indication of a specific immune reaction against the implant. Our findings showed that the sIL-2r and TNF-alpha serum level did not change. The IL-6 level was not significantly altered, but was higher in patients with TiAIV prostheses than in those with a CrCoMo implant and in patients with cemented prostheses. The IL-1beta level was found to be higher in those with a TiAIV cemented prosthesis than in the control group (p=0.0001) and other groups of patients (p=0.003 v uncemented TiAIV, p=0.01 v cemented CrCoMo, p=0.001 v uncemented CrCoMo). The GM-CSF level significantly increased in patients compared with healthy subjects (p=0.008), and it was higher in those with cemented than with uncemented implants (p=0.01). Only patients with cementless CrCoMo prostheses had levels of GM-CSF similar to those of the control group. The highest GM-CSF concentrations were observed in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs) in the last months before revision (p=0.04). In addition, when massive osteolysis was observed, the level of GM-CSF tended to decrease to that of the control group.

Osteosarcoma as a primary second tumor in a patient with nonhereditary retinoblastoma.

A case of osteosarcoma of the distal femur 13 years after the occurrence of a unilateral nonhereditary retinoblastoma is reported. The karyotype of circulating lymphocytis was found to be normal. The existence of a linkage between the two neoplasms due to a subtle chromosomal abnormality is discussed.

Radio-induced sarcomas in survivors of Ewing's sarcoma.

Of 255 cases of Ewing's sarcoma recorded at the Bone Tumor Center of the Rizzoli Orthopaedic Institute, 78 patients (irradiated and with a follow-up of longer than 3 years) were considered "at risk" for the development of a second radio-induced sarcoma (RIS). Three of the 78 patients developed an RIS in the irradiated field. Theoretical and statistical analyses were carried out considering different modalities of local treatment. Statistically, the only significant factor was related to the irradiation dose. Surgical resection seems to prevent RIS.

Neoadjuvant chemotherapy for localized Ewing's sarcoma of the extremities: preliminary results of a protocol which uses surgery (alone or followed by radiotherapy) for local control.

From June 1983 to December 1985, thirty-eight patients with localized Ewing's sarcoma of the extremities were treated with a protocol that consisted of an initial nine week period of polychemotherapy (vincristine, adriamycin and cyclophosphamide) followed by local therapy and additional chemotherapy (vincristine, adriamycin, cyclophosphamide and dactinomycin) for one year. As local treatment all patients were offered surgery; thirty-two accepted and six refused. These six patients were locally treated with radiotherapy alone (50 Gy). In the remaining patients an amputation was performed in one case and a resection in thirty-one. In resected patients when a wide margin was achieved (24 cases) no further local treatment was performed; when it was marginal (5 cases) or intralesional (2 cases) radiotherapy at lower doses (40 Gy) followed. At mean follow-up of thirty-seven months the percentage of continuously disease-free patients was 50% for those treated with radiotherapy, 76% with surgery, and 85% with surgery and radiotherapy. Eight patients developed metastatic disease and two patients had local recurrence and metastases. The local recurrences were seen in one patient locally treated with surgery and in one locally treated with radiotherapy. Nine major local complications were observed: three in patients treated with radiotherapy, five in patients treated with surgery, and one in a patient treated with surgery and radiotherapy. These results indicate that after induction chemotherapy conservative surgery is possible in almost all cases of Ewing's sarcoma of the extremities and that such treatment is better than radiotherapy alone as local therapy.

CT-based surgical planning software improves the accuracy of total hip replacement preoperative planning.

The present study is aimed to compare accuracy and the repeatability in planning total hip replacements with the conventional templates on radiographs to that attainable on the same clinical cases when using CT-based planning software. The sizes of the cementless components planned with new computer aided preoperative planning system called Hip-Op and with standard templates were compared to those effectively implanted. The study group intentionally included only difficult clinical cases. The most common aetiology was congenital dysplasia of hip (65.6%). The Hip-Op planning system allowed the surgeons to obtain a preoperative planning more accurate than with templates, especially for the socket. Assuming correct a size planned one calliper above or below that implanted the accuracy increased from 83% for the stem and 69% for the socket when using templates to 86% for the stem and 93% for the socket when using the Hip-Op system. The repeatability of the Hip-Op system was found comparable to that of the template procedure, which is much more familiar to the surgeons. Furthermore, the repeatability of the preoperative planning with the Hip-Op system was consistent between surgeons, independently from their major or minor experience. The study clearly shows the advantages of a three-dimensional computer-based preoperative planning over the traditional template planning, especially when deformed anatomies are involved. The surgical planning performed with the Hip-Op system is accurate and repeatable, especially for the socket and for less experienced surgeons.

Severe wear from retrieved alumina-on-alumina coupled implant: a case report.

This study details the in vivo wear behavior of an alumina acetabular cup and a femoral head on a retrieved non-cemented hip prosthesis. A commercial alumina ceramic-on-ceramic prosthesis was retrieved from a patient previously treated for bilateral hip arthrosis in "coxa profunda". Massive wear was found on the retrieved alumina ceramic head and acetabular cup. The total measured penetration depth was 1.9 mm while the total calculated weight loss for the acetabular cup was 6.06 g. The study underlines the head-cup instability caused by cup loosening as major cause of severe ceramic wear.

[Therapy of non-metastatic Ewing's sarcoma (pelvis excluded). Results obtained in 48 cases combining local therapy (radiation and/or surgical) and adjuvant chemotherapy with vincristine, adriamycin, dactinomycin and cyclophosphamide]. / Terapia del sarcoma di Ewing non metastatico (pelvi esclusa). Risultati ottenuti in 48 casi associando alla terapia locale (radiante e/o chirurgica) una chemioterapia adiuvante con vincristina, adriamicina, dactinomicina e ciclofosfamide.

Combined therapy was used on a consecutive series of 48 patients with extrapelvic Ewing's sarcoma at the Rizzoli Orthopaedic Institute. The adjuvant chemotherapy protocol (VCR, ADM, D-ACT, EDX) was identical in all patients whereas local treatment consisted of amputation, resection and radiation treatment or radiation alone. At a mean follow-up of 58 months (39-78) 30 patients (60%) were free of the disease. This is a significantly higher percentage than that obtained in the same period with adjuvant chemotherapy using only 3 drugs (VCR, ADM, EDX). As far as the type of local treatment is concerned, the percentage of local recurrences and metastases was lower when the primary lesion was treated with surgery or surgery combined with radiotherapy, rather than radiation treatment alone. These suggest that if associated with radiation treatment and chemotherapy, surgery can play an important role that should be considered in the treatment of extrapelvic Ewing's sarcoma.

A software simulation of tibial fracture reduction with external fixator.

In modern orthopaedic practice, circular external fixators are frequently preferred to plaster cast for various reasons. The realignment of the two fractured bone segments is usually performed under a continuous fluoroscopy checking which involves a long radiation exposure time for both patients and surgeon. In order to overcome this problem, a computer controlled external fixator is under development. One relevant problem which this project faced in its initial stage was the difficulty to define in geometrical terms the manual reduction trajectory normally adopted by the surgeon. Basically it was a typical problem of empirical knowledge transfer from the surgeon to the engineer. Thus, it was necessary to create a common ground where the two experts could carry out the necessary analyses in order to define an empirical algorithm capable of suggesting a correction trajectory. The problem was solved by developing a simulation program called S.E.R.F. (Simulation Environment of a Robotic Fixator) provided with an extremely powerful graphic output, able to visualize the whole reduction trajectory from any viewpoint in space. The authors suggest the use of this kind of tool every time the techno-clinical information exchange is a critical issue.

Investigations on the wear behaviour of the temporary PMMA-based hip Spacer-G.

Total hip replacement has become one of the most successful orthopaedic procedures. However, complications due to infections may give serious problems and have devastating consequences for the hip implant. The use of a temporary three-dimensional polymethylmethacrylate (PMMA) cement spacer may be an alternative to solve infections in hip implants, improving the lives of patients awaiting reimplantation. In order to evaluate their wear behaviour, five PMMA Spacer-G femoral heads were tested against five post-mortem pelves in a hip joint simulator with bovine calf serum as lubricant. The surface of the worn spacers was characterized by scanning electron microscopy (SEM) analysis; all the samples revealed a similar morphology, showing areas characterized by different degrees of wear. Particle debris was isolated from the lubricant and PMMA particles and bone fractions were quantified. The amount of debris was found to be higher than where no-temporary prostheses were used. However, this result is acceptable since wear debris is removed by lavage irrigation when the Spacer-G is explanted. On the basis of these data, it is considered that the use of the cement Spacer-G could be a promising approach to the treatment of complicated infections of the hip joint. Therefore, Spacer-G is worthy of further research.