Allograft sterility as exemplified by human immunodeficiency virus and sterilization by irradiation.
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Biomedical subjects
Publications and source records attributed to P Hernigou.
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We developed methods for inactivating the human immunodeficiency virus by heat and ionizing radiation and tested the effects of these treatments on the mechanical strength of bone. Simultaneous use of heat and radiation caused a considerably greater inactivation of HIV than the additive effects of the two separate treatments, but also caused a significant reduction in the maximum load sustained by the bone specimens tested with an Instrom machine. Application of the same doses but given in the sequential fashion of radiation followed by heat also caused marked inactivation of HIV and had less effect on the mechanical strength of the bone.
OBJECTIVE: To measure the volume of osteonecrosis in 30 patients with disease in both hips (one side with collapse and the other without at Ficat stage I). METHOD: The volume of the osteonecrosis was measured by magnetic resonance imaging. RESULTS: The progression to collapse was influenced by the size of the lesion in each patient. The first collapsed hip was that with the largest volume of osteonecrosis. CONCLUSION: The volume of the osteonecrotic lesion on the second hip (stage I without collapse) is a good predictor of the time to collapse of this second hip.
The risk of articular penetration during tibial nailing is well known, but the incidence of unrecognised damage to joint cartilage has not been described. We have identified this complication in the treatment of tibial fractures, described the anatomical structures at risk and examined the most appropriate site of entry for tibial nailing in relation to the shape of the bone, the design of the nail and the surgical approach. We studied the relationship between the intra-articular structures of the knee and the entry point used for nailing in 54 tibiae from cadavers. The results showed that the safe zone in some bones is smaller than the size of standard reamers and the proximal part of some nails. The structures at risk are the anterior horns of the medial and lateral menisci, the anterior part of the medial and lateral plateaux and the ligamentum transversum. This was confirmed by observations made after nailing 12 pairs of cadaver knees. A retrospective radiological analysis of 30 patients who had undergone tibial nailing identified eight at risk according to the entry point and the size of the nail. Unrecognised articular penetration and damage during surgery were confirmed in four. Although intramedullary nailing has been shown to be a successful method for treating fractures of the tibia, one of the most common problems after bony union is pain in the knee. Unrecognised intra-articular injury of the knee may be one cause of this.
PURPOSE OF THE STUDY: To improve function after pelvic resection involving theacetabulum we have used an anatomic composite implant built with screws and cement. MATERIAL AND METHOD: Since 1990, 27 patients with peri-acetabular bone sarcoma have been treated by extensive resection followed by "hand on innominate prosthesis with constrained total hip prosthesis. The hand on innominate prosthesis was made of a titanium cup, a set of long titanium screws and 2 or 3 packs of gentamycin loaded ciment. RESULTS: Many postoperative complications were observed; deep infection (15 p. 100), hip prosthesis dislocation (33 p. 100) and local recurrence (17 p. 100). Nine patients (33 p. 100) had to be reoperated. Nevertheless at last follow up 24 patients still had their composite prosthesis. The mean functional result, rated according to a modified Enneking's staging system, was 83 p. 100 with unlimited walking without support, average hip flexion 100 degrees, length discrepancy less than 1 centimeters. DISCUSSION: These results were similar to those described in the literature for custom made innominate prosthesis and much better than those of alternative reconstructive procedures. Hand on composite prosthesis is cheaper, easier, more adaptable and enables better anchorage than custom-made prosthesis. Such a procedure can be used even after total iliac wing resection. CONCLUSIONS: The advantages of such procedure pleads for using it extensively after acetabular resection. But long term follow up is necessary to validate indications.
A total of 156 ceramic versus ultra-high-molecular-weight polyethylene hip prostheses were followed for a minimum of 10 years to compare the outcome of the femoral component in 2 groups: those with and those without radiologically detectable voids in the cement mantle. No significant difference was observed. In this series, voids with a 5-mm diameter had no effect on loosening of the femoral component over a 10-year period.
Patients with total hip arthroplasty were screened for the presence of proinflammatory cytokines in the systemic circulation. Only increased levels of interleukin-6 were detected in patients having had total hip arthroplasty more than 10 years ago. These increased levels of interleukin-6 were associated with a decrease in bone mineral density associated with polyethylene wear and with radiologic osteolysis in some patients. These abnormalities were not found in control subjects without total hip arthroplasty or in patients who had a prosthesis in place for less than 6 years. The elevation in interleukin-6 levels found in patients with the oldest prostheses could constitute a marker for periprosthetic osteolysis.
We have evaluated bone-marrow activity in the proximal femur of patients with corticosteroid-induced osteonecrosis and compared it with that of patients with osteonecrosis related to sickle-cell disease and with a control group without osteonecrosis. Bone marrow was obtained by puncture of the femoral head outside the area of necrosis and in the intertrochanteric region. The activity of stromal cells was assessed by culturing fibroblast colony-forming units (FCFUs). We found a decrease in the number of FCFUs outside the area of osteonecrosis in the upper end of the femur of patients with corticosteroid-induced osteonecrosis compared with the other groups. We suggest that glucocorticosteroids may also have an adverse effect on bone by decreasing the number of progenitors. The possible relevance of this finding to osteonecrosis is discussed.
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PATIENTS AND METHODS: A retrospective study of 110 adults with sickle cell anemia (SS genotype) was conducted to determine the frequency of complications of sickle cell osteonecrosis of the shoulder in childhood. The glenohumeral joint was evaluated on plain anteroposterior and lateral radiographs of the shoulder. RESULTS: Mean time since osteonecrosis of the shoulder was 24 years. Radiographic abnormalities were seen in 106 of the 220 shoulders (48.2%). Both shoulders were affected in 86% of cases and at least one hip in 96%. Radiographic abnormalities included isolated caput magna, caput plana, a short humeral neck and ascension of the tuberosities. Twelve shoulders exhibited glenoid fossa abnormalities, which consisted in complete or partial hypoplasia. Evidence of glenohumeral osteoarthritis was seen in 11 shoulders. DISCUSSION: The shoulder abnormalities seen in our patients were probably due to growth disturbances in the proximal humerus secondary to osteonecrosis of the humeral head during childhood. They were common but less likely to produce functional impairment than osteonecrosis-related lesions of the hip. However, some patients had premature osteoarthritis and geometric shoulder abnormalities responsible for functional loss in adulthood.
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PURPOSE OF THE STUDY: Within an anatomical and a clinical study, the authors employed computerized tomographic scans to evaluate the risks of anterior surrounding tissues injuries during screw insertion. MATERIAL AND METHODS: CT scans of 20 patients suffering from cardiac disease were reviewed retrospectively. Scans through the thoracic and lumbar spine were obtained using 6 mm slice thickness. These examinations were performed with intravenous contrast medium. Measurements of vessel diameters and distance of the soft tissues situated directly anterior to the spine were done. A retrospective study of 61 pedicle screws implanted for spine fractures evaluated the penetration of the anterior vertebral cordex with X rays and CT scans. RESULTS: Computerized tomographic scans of the thoracic and lumbar spine of the 20 patients in the control group confirmed proximity of the posterior mediastinal structures to the anterior vertebral cortex. Many structures of the posterior mediastinum were within five millimeters of the anterior vertebral cortex and thus were at risk: aorta, azygos vein, vena cava, parietal pleura and lungs. The theoretical risk of unrecognized screw penetrations evaluated on geometric shape of the anterior vertebral body is as high as 21 per cent when screw position is only seen with an antero posterior and a lateral X Ray. In the other group, computerized tomographic scans showed that 30 per cent of the implanted screws were outside the boundaries of the anterior thoracic spine. DISCUSSION AND CONCLUSION: Two orthogonal incidences do not enable determination of whether the extremity of the screw is slightly outside the anterior cortex of the vertebral body. However the geometric shape of the anterior vertebral body enables peroperative definition of a safety zone on two orthogonal incidences. Even if a breach of a few millimeters of the anterior cortical boundaries of the vertebral body may not initially damage the adjacent soft-tissue structures, chronic irritation may result in late damages of these structures. The use of metallic markers and the respect of a safe vertebral zone on X Rays could guide the choice of the appropriate screw length.
PURPOSE: The purpose of this study was to determine, when assuming the worst case scenario of bone contamination, the sterility assurance level in bone transplantation treated by irradiation and after donor screening. MATERIAL AND METHODS: The virus: We employed the HIV-1, LAV-1 as our reference strain, which has always been cultured on normal human cells (and has therefore never been in contact with cell lines). To test viral virulence, we used a very sensitive cell line: MT2 cell line, a T lymphoblastoid cell line which is HTLV-I positive and is sensitive to HIV-1/LAV-1 infection. It was maintained in RPMI 1640 culture medium containing 10 per cent heat-inactivated fetal calf serum (Boehringer Mannheim), 2 mM L-glutamine (Boehringer Mannheim) and 1 per cent antibiotics (PSN 100 x, Gibco). Cell concentration was 100,000 cells per milliliter. Irradiation was performed using an accelerator delivering electrons of 6.2 MeV providing several tens of kilograys in a few seconds. The dose delivered was checked by placing alanine dosimeters at the site of the HIV aliquots. Alanine is a solid amino acid which, when irradiated, gives rise to free radicals; these were counted using electron paramagnetic resonance (relative standard deviation of less than 1 per cent). RESULTS: 25 kilograys irradiation of 316,227 TCID50/ml at -80 degrees C led to a considerable titer reduction (3 logs) with 316 TCID50/ml remaining. According to the technique's sensitivity (100 TCID50/ml) and to the sensitivity with which the dose of irradiation can be measured (less than 1 per cent), the D10 value with "99 per cent confidence limits" was between 8.3 kilograys and 7.2 kilograys. Assuming the worst characteristics of irradiation, we have chosen 8.3 kilograys as the D10 value for -80 degrees C. DISCUSSION: Considering a mean level of contamination of 30 TCID50 per milliliter of plasma during the asympomatic phase of infection, the reduction of the transmission risk of HIV by a femoral head allograft was calculated in the best case to be only 5 per cent when performed at 25 kilograys. Irradiation cannot be considered as a process able to achieve sterility of the graft and has to be associated to an extensive screening. However irradiation associated with appropriate screening of donors decreases the risk of transmission of the disease under one out of one million in femoral allograft implantation.
Plain radiographs show only two dimensions of a three-dimensional object. On anteroposterior and lateral radiographs an implant may appear to be safely within the head of the femur although surface penetration has occurred. We have attempted to identify this complication in the treatment of fractures of the femoral neck and have analysed the position of a screw or pin in the femoral head and neck on the basis of orthogonal frontal and lateral radiographs. A retrospective analysis of 60 cases of osteosynthesis of fractures of the femoral neck confirmed the risk of non-recognition of articular penetration or breaking of the cortex of the neck during surgery. Unrecognised screw penetration of the hip was observed in 8% and of the posterior part of the neck in 10%. The risk differs according to the type of fracture: it is greater in the coxa valga produced by Garden-I fractures of the femoral neck.
UNLABELLED: The bone-marrow activity in the iliac crest of eleven patients who had idiopathic osteonecrosis of the hip and thirty patients who had osteonecrosis of the hip that was related to corticosteroid therapy (fourteen patients) or to alcohol abuse (sixteen patients) was compared with that in two groups of control subjects who did not have osteonecrosis (thirty-three healthy bone-marrow donors and thirty-four patients who had been managed with bone-marrow grafting for a non-union). Cultures of granulocyte-macrophage progenitor cells and fibroblast colony-forming units were performed to assess the activity of hematopoietic stem cells and stromal cells. The activity of stem cells in both the hematopoietic and the stromal compartment of the bone marrow was decreased in the patients who were receiving corticosteroids or who abused alcohol, as compared with that in the two groups of control subjects. The patients who had idiopathic osteonecrosis also had a decrease in bone-marrow activity compared with the control subjects. CLINICAL RELEVANCE: Our findings suggest that patients who are receiving corticosteroid therapy or who abuse alcohol have decreased activity of bone-marrow cells. Whether this decrease is related to the osteonecrosis could not be determined, as our study did not include control subjects who had a history of alcohol abuse or who were receiving corticosteroids but did not have osteonecrosis. However, it is possible that the reduced bone-marrow activity was related to the osteonecrosis, as patients who had idiopathic osteonecrosis also had decreased bone-marrow activity. The study of pathological alterations in the bone marrow outside the necrotic zone may provide important insights into the pathophysiology of osteonecrosis.
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PURPOSE OF THE STUDY: The recent observations that osteoblasts develop from a stem cell found in the medullary stroma suggest that, as already suspected in classical histological studies, many consolidation mechanisms are based on bone marrow. Since cells characteristics can now be studied in tissue culture, it has become possible to investigate the activity of the bone marrow in non union. The working hypothesis for this study was: if the bone marrow plays a part in bony callus formation, bone marrow from non union site should manifest anomalous activity whatever the origin of the focus sampled. Therefore, the aim of this study was to seek in vitro, using cell cloning techniques, anomalies of bone marrow from non union site. MATERIALS: The study characterizes the bone marrow from 35 non union sites, not only with respect to the medullary stroma but also the hematopoietic compartment. In this study, we look for systemic anomalies which could explain susceptibility to non union, we also compare in vitro activity of bone marrow taken from non union with others samples taken from the iliac crest of the same patient. METHODS: The cell density in the bone marrow in these sites was studied in vitro with material taken from the non union site. Samples were taken by aspiration with a trocar located by image intensification. Assays of CFU-GM were chosen to quantify the hematopoietic activity of the marrow, and of CFU-F to quantify stroma cells activity. Cell densities in the non union site were compared to those in patients' own iliac crests, and also to iliac crests densities of a control population of bone marrow donors. RESULTS: The bone marrow of non union site contained low levels of progenitor cells. Especially surprising was that progenitors were also sparse in the bone marrow of the iliac crest of patients with non union, compared with control bone marrow donors. In several cases, certain general factors are probably responsible for the abnormally low levels of progenitor cells, not only in the non union site, but also in the iliac crest.