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Biomedical subjects

N Passuti

Publications and source records attributed to N Passuti.

At least 19 recordsLinked to original sources

Phenotypic and functional analysis of lymphocytes infiltrating osteolytic tumors: use as a possible therapeutic approach of osteosarcoma.

BACKGROUND: Osteosarcoma is the most common type of primary bone tumor. The use of aggressive chemotherapy has drastically improved the prognosis of the patients with non-metastatic osteosarcomas, however the prognosis of the patients with metastasis is still very poor. Then, new and more effective treatments for curing osteosarcoma, such as immunotherapy are needed. Tumor-infiltrating lymphocytes (TIL) have been involved in the control of tumor development and already assessed with success for the treatment of several cancers including melanoma. While TIL represent a fascinating therapeutic approach in numerous malignant pathologies, there is few report concerning adult bone-associated tumors including osteosarcoma. METHODS: Human TIL were isolated and characterized (phenotype, lytic activity) from twenty-seven patients with bone-associated tumors (osteosarcoma, Ewing's sarcoma, giant cell tumor, chondrosarcoma, plasmocytoma and bone metastases). Similar experiments were performed using rat osteosarcoma model. RESULTS: While TIL with a main CD4+ profile were easily isolated from most of the tumor samples, only TIL extracted from osteosarcoma were cytotoxic against allogeneic tumor cells. In all cases, TIL lytic activity was significantly higher compared to autologous peripheral blood leukocytes. Similar data were observed in rat osteosarcoma model where TIL were characterized by a main CD4+ profile and high lytic activity against allogeneic and autologous tumor cells. Moreover, rat TIL expansion was not accompanied by refractoriness to further activation stimulus mainly by tumor antigens. CONCLUSION: These results demonstrated that TIL therapy could be a very efficient strategy for the treatment of adult osteosarcoma.

Adolescent↗

Bilayered calcium phosphate coating to promote osseointegration of a femoral stem prosthesis.

A bilayered bioactive-gradient coating, consisting of a superficial layer of biphasic calcium phosphate (BCP) and a deep layer of hydroxyapatite (HA), promotes faster osseointegration and higher shear strength in non-loading conditions than do monolayer BCP or HA coatings. This study evaluated the biofunctionality of this coating in weight-bearing conditions at 6 and 12 months. The coating was plasma-sprayed on the metaphyseal portion of a sandblasted Ti6Al4V canine femoral prosthesis implanted using the surgical press-fit technique. An identical uncoated stem served as the control. Metaphyseal bone-to-implant apposition was increased for coated ( approximately 90% and 80% respectively at 6 and 12 months) as compared to uncoated implant ( approximately 7% at 6 and 12 months). Limited bone apposition was observed at the diaphyseal level. After 12 months, the uncoated implant interface consisted of well-organized, active fibrous tissue, whereas only inactive fibrous tissue interposition was observed at diaphyseal levels of the coated implant. At 6 months, the mineralization apposition rate (MAR) was similar, regardless of implant or bone structures. At 12 months, a significant decrease of MAR was observed around the uncoated implant. Transmission electron microscopy studies of the interface showed precipitation of biological apatite crystals in close association with mineralized collagenous bone matrix. Our results suggest a direct relationship between bioactivity and enhanced bone formation. The sandwich coating used is effective in promoting massive metaphyseal osseointegration, which ensures mechanical stability for early weight-bearing and should prevent long-term complications.

Journal Article↗

Efficacy of pentasaccharide on a prethrombosis model based on a calibrated stasis by the increase in up-stream venous pressure.

On a previous model using Wessler's principle in the rat, we have demonstrated that a partial ligature of the inferior vena cava leading to a 40% increase in up-stream venous pressure was thrombogenic only in association with the infusion of low dose of thromboplastin (90 microg/kg). In these thrombogenic conditions, the infusion of pentasaccharide (Arixtra, fondaparinux) should lead to a strong inhibition of thrombus formation. Therefore, we performed on five groups of 10 rats: stasis alone (group S) with a 40% increase in up-stream venous pressure; stasis and thromboplastin (group ST90); and stasis, thromboplastin and pentasaccharide (groups SPT50, SPT100 and SPT250) at three different dosages (50, 100 and 250 microg/kg). The efficacy of pentasaccharide was measured according to the variations in up-stream venous pressure, thrombus weight and thrombin-antithrombin complexes levels. Only 250 microl/kg pentasaccharide significantly reduced the thrombus weight in comparison with group ST90 (5 mg versus 23.8 mg, P = 0.01) but it was not sufficient to induce a return to the basic state (5 mg versus 0.2 mg in group S, P = 0.049). Thrombin-antithrombin complex levels measured at the end of the experiment were significantly reduced in comparison with group ST90 (16.7 versus 57.8 mg, P = 0.01) and were not statistically different from group S (16.1 versus 16.6 mg, P = 0.65). In conclusion, in a very borderline model toward thrombogenesis, pentasaccharide was able to reduce thrombus weight and abolished biological hypercoagulability.

Animals↗

Metatarsal giant cell tumors and giant cell reparative granuloma are similar entities.

Light and electron microscopic investigations and studies of the resorption ability in vitro of giant cells were done in two patients with giant cell osteolytic lesions of metatarsal bone. Giant cells harvested from both patients were similar in morphologic features and ability to resorb dentin. After other diagnoses of osteolytic lesions of metatarsal bone were ruled out, one lesion was considered a giant cell reparative granuloma and the other a true giant cell tumor of bone. Clinical, radiologic, ultrastructural, functional studies, and data in the literature, indicated that giant cell reparative granuloma only can be differentiated from giant cell tumor by younger age at diagnosis and the occurrence of giant cell clusters. All other features (cortical erosion, high rate of recurrence, hemorrhage areas, predominant intercellular collagenous substance) are characteristic of both lesions. If these two giant cell lesions are different entities, more accurate means are needed to distinguish them.

Adolescent↗

Influence of metal ion solutions on rabbit osteoclast activities in vitro.

The purpose of the present study was to compare the effects of various metal ions (aluminium, chromium, cobalt, gold, iron, strontium, titanium and vanadium) on rabbit osteoclast activities, with respect to their number, size, resorptive capacity and their capacity to release proteinases. Marked heterogeneous osteoclastic behaviour was observed early in culture with metal ions (24 h) in term of resorption parameters. In contrast, protease activities (cysteine-proteinase and metalloproteinase activities) were not modulated in our culture conditions. Aluminium, iron, gold and titanium reduced the number of osteoclasts significantly. Aluminium and gold had no effect on osteoclast-mediated resorption on dentin-slices, although aluminium induced a greater number of very small lacunae. Titanium reduced only the mean surface area per lacunae, cobalt reduced the mean surface area of lacunae and increased their number, and iron reduced both parameters. Strontium had no effect on osteoclast formation and on total dentin slice surface resorbed. However, strontium increased the number of small lacunae formed on dentin-slices by osteoclasts. Chromium had no effect on osteoclast activities. These findings indicate that metal ions induce very early effects on osteoclasts, which can contribute to periprosthetic pathologies via different cellular mechanisms.

Animals↗

Bone remodelling and tumour grade modifications induced by interactions between bone and swarm rat chondrosarcoma.

Chondrosarcoma is currently defined as a malignant cartilage tumour arising de novo or within a pre-existing benign cartilage tumour. Chondrosarcoma can be surgically resected, but all grades have significant rates of local recurrence. The purpose of the present study was to develop an animal intraosseous chondrosarcoma model simulating the progression of human chondrosarcoma and elucidating its behaviour and biology. An intraosseous Swarm rat model was designed to assess interactions between bone and chondrosarcoma. A comparison of tumour grading was carried out according to transplantation site. The effects of chondrosarcoma cells (SRC cells) on the mineralisation capacities of osteoblasts and on osteoclast differentiation were studied in relation to modifications observed in vivo at the cellular level. Transplantation of Swarm rat chondrosarcoma within bone marrow or contiguous to induced periosteal lesions led to extensive bone remodelling with trabecular bone rarefaction and periosteal apposition. Transplantation in close contact to bone but without any periosteal lesion had no effect on bone, suggesting that bone healing factors interact with tumour development. With the intramedullary model, the development of tumours of different grade confirms that bone environment is an important factor in malignancy. A decrease of bone nodule formation was noted after cocultures of SRC cells with rat bone marrow, but there was no modification of osteoclast differentiation after cultures of total rabbit bone cells with SRC cells. These data reveal the importance of interactions between bone environment and tumour in inducing bone remodelling and variations in tumour malignancy.

Animals↗

Intraspinal metallosis causing delayed neurologic symptoms after spinal instrumentation surgery.

STUDY DESIGN: Two cases of intraspinal metallosis causing delayed neurologic symptoms secondary to spinal instrumentation surgery are reported. OBJECTIVE: To present an unusual delayed neurologic complication after spinal instrumentation surgery. SUMMARY OF BACKGROUND DATA: Metal-related complications caused by orthopedic implants have long been a concern in the field of arthroplasty or internal fixation of fractures, but no such complications have been reported for spinal instrumentation. METHODS: Retrospective case report of two patients with degenerative scoliosis who presented with delayed neurologic symptoms months to years after uneventful, but without secondary degenerative changes or dislodgement of the implants. RESULTS: In both reported cases, a granulation-tissue mass characterized by marked metallosis had been formed in the spinal canal adjacent to a loosened laminar hook. CONCLUSIONS: Intraspinal metallosis should be kept in mind as a rare cause of delayed neurologic symptoms after spinal instrumentation surgery. With the metal implants in place, myelography was the sole informative examination for diagnosis.

Back Pain↗

[In vitro assessment of combining osteogenic cells with macroporous calcium-phosphate ceramics].

PURPOSE OF THE STUDY: Bone grafts or bone substitutes are required to fill bone defects resulting from trauma or surgical resection of tumors. Calcium-phosphate ceramics are synthetic bone substitutes which promote new bone formation by osteoconduction. These ceramics possess osteoconductive properties but have no intrinsic osteoinductive capacity. They are unable to induce new bone formation in extraossesous sites. One solution to develop bone substitutes with osteogenic properties would be to associate biomaterials with osteoprogenitors. MATERIALS AND METHODS: We studied the in vitro osteogenic potential of human bone-marrow cells cultured on macroporous calcium phosphate (CaP) ceramic, examining stromal cell proliferation and differentiation. Osteogenic differentiation was evaluated in terms of alkaline phosphatase activity and immunological characterization of the extracellular fibrillar matrix formed by these cells. The specimens were examined by scanning and transmission electron microscopy. RESULTS: Human bone-marrow cells proliferated on CaP ceramic. The proliferating bone-marrow cells expressed an osteoblastic phenotype as shown by alkaline phosphatase activity and synthesis in ceramic pores of an extracellular matrix composed of fibronectin, osteocalcin and collagen I. In addition, numerous microcrystals of apatite precipitated on the fibrillar matrix, producing a mineralized fibrillar network within the ceramic. CONCLUSION: This study demonstrates that human bone-marrow cells cultured on macroporous CaP ceramic do not lose their osteoblastic phenotype even after 21 days of culture, and that they can induce osteogenesis in a CaP ceramic in vitro. This type of new "hybrid material" appears promising for the future.

Bone Marrow Cells↗

Influence of bone environment on ceramic osteointegration in spinal fusion: comparison of bone-poor and bone-rich sites.

Quantitative experimental data showed differences in bone quality and ceramic incorporation between bone-rich and bone-poor implantation sites. Bone in-growth was significantly lower for ceramic implanted at a lumbar intertransverse than a laminar site. Bone-marrow enrichment of the lumbar intertransverse site (regarded as bone-poor) greatly facilitated ceramic osteointegration. The vertebral interbody site, despite theoretical richness in osteogenic precursor cells, might be bone-poor at the time of grafting as compared to the reference iliac crest site. These data have important clinical implications concerning the potential benefit of enriching both bone-poor and bone-rich sites.

Bone Marrow Transplantation↗

Potential synergies between matrix proteins and soluble factors on resorption and proteinase activities of rabbit bone cells.

Human growth hormone (GH) has recently been found to stimulate osteoclastic resorption, cysteine-proteinase and metalloproteinase activities (MMP-2 and MMP-9) in vitro via insulin-like growth factor-I (IGF-I) produced by stromal cells. The present study investigated the effects of two extracellular matrix components (vitronectin and type-I collagen) on hGH- and hIGF-1-stimulated osteoclastic resorption and proteinase activities in a rabbit bone cell model. After 4 days of rabbit bone cell culture on dentin slices with vitronectin coating, hGH and hIGF-1 stimulated bone resorption and hIGF-1 upmodulated cysteine-proteinase activities. MMP-2 expression (but not resorption, cathepsin or MMP-9 activities) was upmodulated by hGH and hIGF-1 on dentin slices coated with type I collagen as compared to those without coating. Then, vitronectin was synergistic with hIGF-1 in the regulation of cysteine-proteinase production whereas collagen showed synergy with hGH and hIGF-1 in the regulation of MMP-2 production. Anti-alphavbeta3 totally abolished the effects of hGH and hIGF-1 on metalloproteinase release, but had no influence on cathepsin release. The results suggest that cysteine-proteinase modulation is not mediated by alphavbeta3 integrin (strongly expressed on osteoclastic surface) whereas the resorption process and metalloproteinase modulation are clearly mediated by this integrin. Our finding about the collagen coating also suggests that hGH- and hIGF-1-stimulated MMP-2 activity are mediated, along with alphavbeta3 integrin, by another adhesion molecule.

Animals↗

[Subfascial lipomatous tumors: management in a series of 37 consecutive cases].

PURPOSE OF THE STUDY: The prognosis of subfascial lipomatous soft tissue tumors depends greatly on their histological type ranging from benign lipomas that cause little local or general problems to the severe prognosis of liposarcomas that exhibit both local and distant extension. However, the clinical presentation of the two types of tumors may be similar and thus quite misleading, sometimes leading to inappropriate management and severe consequences. The main objective of this study was to determine whether the preoperative work-up in patients treated for musculoskeletal tumors within our recruitment zone is adequate, allowing appropriate therapeutic decisions. In addition, we wanted to know what explorations are most pertinent for the differential diagnosis between benign and malignant subfascial lipomatous soft tissue tumors. MATERIAL AND METHODS: Thirty-seven patients with subfascial tumors were included in this study. There were 16 with benign lipomas and 21 with liposarcomas. All the patients with benign lipomas but only 9 (43%) of those with liposarcoma had received initial care within our recruitment zone before final diagnosis. Two cases had been referred after biopsy and 1 after resection by morcellation; the 9 others were secondary referrals after tumor recurrence. Only 5 of these 12 referred patients had had an MRI exploration prior to surgery, 2 with an erroneous interpretation. An MRI series was obtained for all the patients with benign lipoma and for the 9 with liposarcomas who attended our units directly. A biopsy was also obtained in case of suspected liposarcoma. Two radiologists blinded to the final diagnosis reviewed the available MRI to assess their diagnostic value for subfascial lipomatous soft tissue tumors. RESULTS: No case of recurrence, after marginal resection (10 cases) was noted for lipomas. Six are under observation with regular MRI (with no change in size or signal). Four patients with liposarcoma died from their disease (19%) and 2 who had undergone "curative" resection had a recurrence (12%). Incorrect or imprecise (incomplete, incorrectly interpreted or no MRI) preoperative diagnosis led to additional morbidity with 3.4 surgical procedures (mean per patient) compared with 1 in patients who had had undergone a complete work-up and whose diagnosis was established after multidisciplinary discussions. Among the diagnostic elements available before pathology, only MRI findings had diagnostic value for subfascial lipomatous soft tissue tumors: for benign lipoma positive predictive value=92% and negative predictive value=93%. DISCUSSION: The clinical course of the benign lipomas and the sarcomas in this series confirm the radically different prognosis of these two tumors, both in terms of local extension and survival. Inadequate management in the initial diagnostic stages-i.e. lack of MRI with contrast injection, biopsy and multidisciplinary interpretation prior to treatment-raises the risk of higher morbidity, particularly a significantly greater number of reoperations, and progression to a higher grade of malignancy for two tumors. Our retrospective analysis enabled us to develop a decision making tree for patients with subfascial lipomatous tumors. Prospective validation will be necessary.

Decision Trees↗

A synthetic porous ceramic as a bone graft substitute in the surgical management of scoliosis: a prospective, randomized study.

STUDY DESIGN: A prospective randomized study. OBJECTIVES: To assess the clinical and radiologic performances of a synthetic ceramic as a bone graft substitute in scoliosis surgery. SUMMARY OF BACKGROUND DATA: Surgery on the skeleton frequently requires harvesting of autogenous bone grafts from the pelvis, but this procedure often is complicated by problems. METHODS: Fifty-eight patients with idiopathic scoliosis, ages 13 to 25 years, were treated by posterior correction and arthrodesis using Cotrel-Dubousset instrumentation. Posterior spinal fusion was performed using local bone grafts combined with autogenous iliac bone grafts in 30 patients, and combined with porous biphasic calcium phosphate ceramic blocks comprising hydroxyapatite and tricalcium phosphate in another 28 patients. The patients were observed for a minimum of 24 months after surgery, with a mean postoperative observation time of 48 months. The results were assessed clinically and radiographically. RESULTS: Patients in the ceramic group had a lower average blood loss than those in the iliac graft group. They also were free from postoperative local complications in the iliac region, which were experienced by a significantly high proportion of patients belonging to the iliac graft group. Radiography demonstrated successful incorporation of the ceramic blocks within 12 months. The correction of the deformity was maintained similarly and satisfactorily in both groups. CONCLUSIONS: These results justify and favor the use of calcium phosphate ceramics as bone graft substitutes for instrumented posterior spinal fusion in teenagers and young adults. Potentially hazardous harvesting of pelvic bone is no longer necessary for such operations.

Adolescent↗

[Neurogenic mixed evoked potential monitoring during scoliosis surgery: retrospective analysis of 149 cases].

INTRODUCTION: We report a retrospective analysis of spinal cord monitoring with neurogenic mixed evoked potentials (NMEPs) combined with somatosensory evoked potentials (SSEPs) in 149 patients undergoing surgery for spinal deformity. MATERIAL AND METHODS: 149 patients (104 females and 45 males), mean age 28 yrs (13-72 yrs) were studied. NMEPs were elicited by electrical spinal cord stimulation in the rostral part of the surgical field, via two needle electrodes set in the epidural space and in the interspinous ligament above. They were recorded from the sciatic nerve at the knee and the sural nerve at the ankle. SSEPs were recorded from the scalp after stimulation of the posterior tibial nerve at the ankle. A decrease in amplitude of more than 50 p. 100 and/or an increase in latency of more than 10 p. 100 were defined as significant warning criteria. RESULTS: No false-negative result was observed. NMEP modifications did not reach critical value in 143 cases. In 6 cases, significant changes were observed. Moving the stimulation electrodes along the spinal cord allowed spinal lesion localization and helped the surgeon to perform the adapted maneuver, clearly avoiding the occurrence of postoperative neurological defect in 5 of the 6 cases. CONCLUSION: NMEP monitoring is a sensitive and specific method useful for detecting an impending lesion of the spinal cord. NMEPs are also helpful in localizing the spinal level of the lesion. They represent a primary choice tool for neuromonitoring during scoliosis surgery.

Adolescent↗

Successful monitoring of neurogenic mixed evoked potentials elicited by anterior spinal cord stimulation through thoracoscopy during spine surgery.

STUDY DESIGN: Neurogenic mixed evoked potentials were recorded after thoracoscopic spinal cord stimulation in patients undergoing video-assisted spine surgery. OBJECTIVE: To demonstrate the feasibility and value of thoracoscopic spinal cord monitoring. SUMMARY OF BACKGROUND DATA: Video-assisted thoracic surgery recently has been proposed as a new technique for thoracic spine surgery. It can be used for anterior spinal release of patients with severe spinal deformities and for thoracic hernia removal. METHODS: Five patients undergoing video-assisted thoracic surgery for spinal fusion were studied. Neurogenic mixed evoked potentials were elicited by electrodes seated into intervertebral discs through thoracoscopy and recorded from peripheral nerves of the lower limbs. Moreover, the study included the case of a patient with a thoracic hernia who underwent video-assisted thoracic surgery with combined thoracoscopic neurogenic mixed evoked potential and standard somatosensory evoked potential monitoring. RESULTS: Neurogenic mixed evoked potentials were recorded consistently after spinal cord stimulation in all patients. For the patient with a thoracic hernia, neurogenic mixed evoked potentials suddenly disappeared, whereas somatosensory evoked potentials were not significantly modified, leading to surgery interruption. Neurogenic mixed evoked potentials progressively reappeared after a 30-minute delay. Postoperation examination revealed a Brown-Sequard's syndrome with incomplete right motor deficit. CONCLUSIONS: Neurogenic mixed evoked potentials evoked by anterior stimulation through thoracoscopy are of interest for spinal cord monitoring when posterior electrical stimulation is impossible, and they provide reliable information regarding spinal motor pathways.

Adolescent↗