[Endovascular repair of iliocaval arteriovenous fistula complicating lumbar disc surgery]. / Traitement endovasculaire d'une fistule artério-veineuse ilio-cave compliquant une chirurgie discale lombaire.

Vascular complications of lumbar disc surgery are rare. Few cases have been reported. Arteriovenous fistulas are the most common. They are due to anatomical relationships between the last lumbar vertebrae, the corresponding discs, and the iliac vessels; degenerative lesions of the intervertebral discs facilitate instrumental vessel perforation, and operative difficulty. Computed tomography is particularly accurate for making the diagnosis. Treatment strategies consist in surgery or endovascular management. Percutaneous endovascular treatment using a stent-graft is a reasonable option for treating arteriovenous fistula. We describe the case of a 50-year-old patient who developed an iliocaval arteriovenous fistula following lumbar disc hernia surgery. The lesion was excluded by a stent-graft. The postoperative period was uneventful.

Osteoblast-induced osteoclast apoptosis by fas ligand/FAS pathway is required for maintenance of bone mass.

The interplay between osteoblasts and osteoclasts has a crucial role in maintaining bone homeostasis. In this study, we reveal that osteoblasts are capable of inducing osteoclast apoptosis by FAS ligand (FASL)/FAS signaling. Conditional knockout of FASL in osteoblasts results in elevated osteoclast numbers and activity, along with reduced bone mass, suggesting that osteoblast-produced FASL is required to maintain physiological bone mass. More interestingly, we show that osteoblasts from ovariectomized (OVX) osteoporotic mice exhibit decreased FASL expression that results from the IFN-γ- and TNF-α-activated NF-κB pathway, leading to reduced osteoclast apoptosis and increased bone resorption. Systemic administration of either IFN-γ or TNF-α ameliorates the osteoporotic phenotype in OVX mice and rescues FASL expression in osteoblasts. In addition, ovariectomy induces more significant bone loss in FASL conditional knockout mice than in control group with increased osteoclast activity in which the levels of RANKL and OPG remain unchanged. Taken together, this study suggests that osteoblast-induced osteoclast apoptosis via FASL/FAS signaling is a previously unrecognized mechanism that has an important role in the maintenance of bone mass in both physiological conditions and OVX osteoporosis.

Assessing the economic impact of Rx-to-OTC switches: systematic review and guidelines for future development.

INTRODUCTION: Switching drugs from prescription to non-prescription status (Rx-to-OTC) presents a unique set of challenges and opportunities to policy-makers and the industry in terms of managing health outcomes, pharmaceutical spending, and steering of consumer choices of therapy. Decision-analytic models are used to address uncertainty and produce reasonable estimates of the economic impact of switches for payers. This article presents a critical literature review of existing models which assess the economic impact of Rx-to-OTC switches, and provides guidelines in which future economic evaluations of Rx-to-OTC switches could be improved. METHODS: A comprehensive search strategy was implemented in Medline and Embase, to retrieve published economic evaluations on Rx-to-OTC switches from 1995-2010. The research digest of the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) was reviewed for potentially relevant abstracts for the past 3 years. Each model used was critically evaluated in terms of structure, relevance of inputs, methodology used, and robustness of results. RESULTS: Worldwide, the economic impact of Rx-to-OTC switches has only been evaluated in a total of 12 peer-reviewed publications. Ten out of 12 studies were US-based, and two European-based. The models covered various disease categories, including allergy, hypercholesterolemia, gastroenterology, contraception, pulmonology, and virology. Seventy-five per cent of the models predicted cost savings for payers and patients. Limitations of the models mainly included use of strong assumptions and non-inclusion of specific populations due to lack of data. Guidelines were developed to help future model development. They cover structural issues on decision context, health states, and clinical outcomes, and other considerations for model specifications. CONCLUSIONS: Although reviewed studies lacked quality, this review of economic evidence of Rx-to-OTC switches suggests that switches may produce cost savings to public and private payers. This is especially important in light of the trend towards more switches.

Knee arthrodesis using a vascularized fibular rotatory graft after tumor resection.

INTRODUCTION: Knee arthrodesis is one of the reconstruction options for limb preservation after malignant tumor resection. Vascularised rotatory fibular transfer allows biological and, thus,definitive reconstruction. The goal of this work was to analyse the results of knee arthrodesis with vascularised fibular graft after tumor resection and to discuss the reliability of this technique. PATIENTS AND METHODS: We report a retrospective series of 13 patients with an average age of 29.6 years. The pathological diagnosis was bone sarcoma in 12 cases and synovial chondrosarcoma in one case. Resection/arthrodesis was undertaken as the primary procedure in 11 cases.In two cases, arthrodesis was indicated after failure of an endoprosthesis. Reconstruction was achieved with a vascularised fibular rotatory transfer in all cases. For stabilisation, an external fixator was utilised in eight cases, a femorotibial nail in three cases, and a plate in two cases.Mean follow-up was 6 years. RESULTS: We encountered infection in 53% of cases, mechanical complications in 53% of cases,and nerve palsy in 23% of cases. Four patients died from metastases (only one had arthrodesis complete union). In the nine surviving patients, arthrodesis was fully united in seven cases,after an average period of 36 months. The functional score average (Enneking classification)was 20 points. DISCUSSION: Knee arthrodesis after tumor resection is a complex technique. Septic complications and mechanical failure are frequent regardless of the technique employed. They are related to the extent of bone sacrifice but also to that of soft tissues. The use of vascularised fibula alone and stabilisation by external fixation were the main shortcomings in this series. TYPE OF STUDY RETROSPECTIVE: Level IV.

[Lanthanides and microanalysis. Effects of oral administration of two lanthanides: ultrastructural and microanalytical study]. / Lanthanides et microanalyse. Effets de l'administration orale de deux lanthanides :etude ultrastructurale et microanalytique.

The subcellular localization of cerium and lanthanum in the intestinal mucosa was studied after oral administration of cerium chloride or lanthanum chloride or lanthanum chloride followed 30 minutes after of cerium chloride to young adults Wistar rats. Two methods of observation and microanalysis were used. The transmission electron microscopy revealed the presence of dense electron granulations in the lysosmes of the duodenum enterocyte, when these elements were administrated simultaneously. The ion mass microanalysis permits to detect the presence of La and Ce as bright points outlining the intestinal villi. These points correspond to the lysosomes containing the granulations previously described. These granulations are formed by the cerium and the lanthanum associated to the phosphor and forming probably insoluble salts of Ce/La phosphate.

[Epithelioid hemangioendothelioma of bone complicated by femoral fracture]. / Hémangio-endothéliome épithélioïde osseux compliqué d'une fracture du fémur.

A 54-year-old man was seen with a fracture of the left femur. Plain radiographs revealed a 40-mm lytic centromedullary lesion. Magnetic resonance T1- and T2-weighted sequences showed high and low signals. After stabilization of the fracture, the tumor was removed followed by reconstruction with a vascularized fibula. The pathological examination demonstrated proliferation of non atypical CD34 and CD31 positive epithelioid cells with few lumens, accompanied by abundant fibrous stroma, sometimes masking tumor cells. Satisfactory motion was achieved with no recurrence at 20 months follow-up. Bone hemangioendothelioma can simulate metastasis and must be distinguished by immunohistochemistry. Prognosis is a subject of debate as the tumor is considered to exhibit intermediate malignancy by some authors while other consider it to be a malignant tumor.

[Polyarthritic manifestations revealing Stickler syndrome]. / Manifestations poly-articulaires révélatrices d'un syndrome de Stickler.

Stickler syndrome, also called hereditary arthro-ophthalmopathy is a dominant disorder, with poly-epiphyseal dysplasia resulting in early osteoarthritis. It usually includes bilateral myopia, that changes little during the follow up period, but can lead to retinal detachment. Children with Stickler syndrome can show facial dysmorphism that may improve with age, but severe anomalies may exist such as Pierre Robin sequence. Our case, a woman, 20-year-old, presents chronic polyarthritis which is an unusual feature of this disease. The diagnosis of Stickler's syndrome is based on polyepiphyseal dysplasia in skeletal radiography and bilateral myopia. Otherwise, this patient has no facial dysmorphism.

[Valgus osteotomy in the treatment of pseudoarthrosis of the femoral neck: 41 cases]. / Ostéotomie de valgisation dans les pseudarthroses du col du fémur: à propos de 41 cas.

PURPOSE OF THE STUDY: Treating hip trauma victims who develop nonunion of the femoral neck remains a challenge in orthopedic surgery. We studied the clinical and radiological outcome after Pauwels osteotomy for valgisation. MATERIAL AND METHODS: This retrospective series included 41 patients (25 men and 16 women), mean age 44.5 years. Initial treatment was surgical in 21 cases and had been insufficient in 91%. Nonunion (subcapital in 53%, transcervical in 40% and basicervical in 7%) had persisted for 16 months. A tight nonunion was present in 65.9% of the cases and the femoral head appeared normal in 70%. Femoral osteotomy was performed for simple valgisation in 78% of the cases with a mean 31.5 degrees correction (range 15 degrees to 50 degrees ). A nail or screwed plate was used for fixation. Results were analyzed at a mean 76 months post-surgery. RESULTS: Bone healing was achieved in 98% of the cases. The only failure was related to inappropriate surgical technique. Necrosis was observed in 16 cases. The functional outcome was very good or good in 82% of the patients. CONCLUSION: Osteotomy for valgisation remains a very good salvage procedure for nonunion of the femoral neck following hip trauma. It can be used for elderly subjects even in the presence of early stage or partial necrosis.

Identification of a polymorphic microsatellite marker in the mouse Fas ligand gene.

We describe the characterization of a polymorphic microsatellite marker, located 1.8 kb downstream of exon 4 in the mouse Fas ligand gene. This (GT) repeat sequence allows the identification of four alleles which can very easily be distinguished by simple agarose electrophoresis.

[Primary chemotherapy with the Rosen T10 protocol before conservative surgery in limb primitive osteosarcomas: results about 56 cases]. / Chimiothérapie première par le protocole T10 de Rosen avant chirurgie conservatrice dans les ostéosarcomes primitifs des mebres: résultats à propos de 56 cas.

We report the results of a prospective Tunisian study using primary chemotherapy followed by conservative surgery in primitive limb osteosarcoma. From January 1988 to January 1998, 56 patients affected by limb osteosarcoma entered in a prospective study of neoadjuvant chemotherapy with the T10 protocol before surgery with a conservative intent. Initial work-up include: clinical exam with tumor measurements, chest and limb X-rays, limb CT-scan or MRI, chest CT-scan, bone scintigraphy and hematological and renal biological exams. Patients receive pre- and post-operative chemotherapy according to the T10 modified protocol. Fifty-six patients (33 M/23 F) with a mean age of 19 years (8 to 28) are included. Mean clinical and radiological tumor size is around 14 cm. Main histologic type is classic osteosarcoma (50% of cases) and 10 patients (9%) presented with initial metastasis; 42 patients on 56 receive the whole pre-operative protocol. Treatment is well tolerated excluding 18 episodes of mucositis, 29 of leucopenia (< grade 3), 7 of thrombopenia (< grade 3), 4 of cutaneous toxicity, 2 of pulmonary toxicity and 3 of nausea-vomiting. We observe 36% of good histological responders and 64% of bad responders to primary chemotherapy, 27 patients on 49 operated (53%) have a conservative surgery and 18 (47%) a radical surgery. With a median follow-up of 51 months (8 to 128), 29 patients remain alive free of disease (15/17 GR and 14/30 BR), 2 are alive with disease, 2 died by toxicity, 14 died by progressive disease and 9 are lost to follow-up with evolutive disease. Five year disease-free survival is 55% for the 46 non metastatic patients. In univariate analysis, seric alkaline phosphatase level (p = 0.0014) and histological response to chemotherapy (p = 0.0218) are significant factors for prognosis.

[Use of Ilizarov fixator in the treatment of post-osteomyelitis pseudoarthroses in children]. / Utilisation du fixateur d'Ilizarov dans le traitement des pseudarthroses post-ostéomyélitiques de l'enfant.

PURPOSE OF THE STUDY: The aim of this study was to emphasize the importance of the distraction osteogenesis technique in the treatment of post-osteomyelitis nonunion. We report 12 cases. PATIENTS AND METHODS: Mean patient age was 9.5 years. There were 7 cases of nonunion of the femur and 5 involving the tibia. Nonunion was associated with 5.9 cm shortening in 10 cases, 8.4 cm circumferential bone defect in 1 case, shortening and bone defects in 6 cases, and shortening and joint deformities in 2 cases. RESULTS: Consolidation was obtained in 11 cases with an average delay of 11.6 months. Infection was eradicated in 75 per cent of the cases. Average residual shortening was 0.4 cm. Joint deformities and axial deviations were corrected at the same time in all cases. DISCUSSION: The advantages of the Ilizarov technique are well known for the treatment of such deformities and musculoskeletal system disorders subsequent to osteomyelitis: nonunion, infection, shortening, joint deformities and malunion.

[Consequences of tibiotalar arthrodesis on the foot. A retrospective study of 36 cases with 8.5 years of followup]. / Etude du retentissement de l'arthrodèse tibio-talienne sur le pied. A propos de 36 cas revus avec un recul moyen de 8 ans et demi.

The authors report the results of a retrospective study of 36 cases of tibiotalar arthrodesis performed in 22 men and 14 women with an average age of 32 years. All patients were reviewed with an average of 8.5 years follow-up. The predominating etiologies were ankle osteoarthritis (15 cases) and neurologic deformities of the foot (13 cases). Arthrodesis was performed using the Meary technique in 60% of cases, using the Charnley technique in 20% and the Crawford-Adams technique or with clamps in the other cases. Fusion was obtained in 97% of cases. Long-term results were assessed using Duquennoy et al.'s scoring system. They were very good or good in 58% of cases, fair in 31% and poor in 11%. The study of distal repercussions of tibiotalar arthrodesis shows progressive deterioration of the subtalar joint in 70% of cases and appearance or increase of degenerative changes in 75% of cases. The final results of the procedure depend on this deterioration; the latter is related with the arthrodesis position. Midtalar joint is a compensation joint showing hypermobility in 40% of cases. Degenerative changes were limited and asymptomatic in 80% of cases. Based on the findings in this study and on the literature, we conclude that the foot should be fixed at 90 degrees or with less than 5 degrees of equinus, with 5 degrees of valgus and 10 to 15 degrees of external rotation.

Structural basis of the gp120 superantigen-binding site on human immunoglobulins.

B cell superantigens (SAg) interact with normal human nonimmune Igs (Igs), independently of the light chain isotype, and activate a large proportion of the B cell repertoire. Recently, the major envelope protein of HIV-1, gp120, was found to exhibit SAg-like properties for B cells with potential pathologic consequences for the infected host. This unconventional mode of interaction contrasts with its binding to immunization-induced Abs, which requires the tertiary structure of the heavy and light chain variable regions. In this report, we have examined the structural basis of the interaction between human Igs and gp120. We found that gp120 binding is restricted to Igs from the V(H)3 gene family and that the two V(H) genes 3-23 and 3-30, known to be overutilized during all stages of B cell development, frequently impart gp120 binding. We also provide evidence that the viral gp120 SAg can interact with only a subset of the human V(H)3+ Igs that can convey binding to the prototypic bacterial B cell SAg protein A from Staphylococcus aureus. Finally, we have identified amino acid positions present primarily in the first and third framework regions of the Ig heavy chain variable region, outside the conventional hypervariable loops, which correlate with gp120 binding. In a three-dimensional sequence-homology model, these residues partially overlap with the predicted SAg protein A binding site for V(H)3+ Igs.

Myocyte enhancer factor-related B-MEF2 is developmentally expressed in B cells and regulates the immunoglobulin J chain promoter.

Immunoglobulin J chain gene expression is induced by the delivery of a lymphokine signal to antigen-activated B cells in a primary immune response. A major interleukin 2 (IL-2)-responsive region that contains two adjacent control elements (JA and JB) exists within the J chain promoter. Transcription factor PU.1 positively regulates J chain gene expression by binding to one of the control elements (JB) in the J chain promoter. In the present study we have determined that a myocyte enhancer factor 2 (MEF2)-related nuclear factor, named B-MEF2, positively regulates the J chain gene promoter activity via the second control element (JA). An in vitro translated MEF2 family member, MEF2C, was found to bind the JA site with identical properties as endogenously expressed B-MEF2 in B cell lines. Moreover, in vivo experiments showed that a dominant negative mutant of MEF2C blocked B-MEF2 regulation of the J chain promoter. Consistent with its role as positive regulator of J chain gene expression, B-MEF2 levels were enhanced in highly differentiated B cells. In addition, induction of an IL-2-responsive presecretor cell line BCL1 with IL-2 or IL-5 (which up-regulates J chain gene expression) resulted in an increased expression of B-MEF2. We conclude that a MEF2-related transcriptional factor, B-MEF2, acts as a stage-specific positive regulator of J chain gene expression in the B cell lineage.

[Giant cell tumors of the distal end of the radius treated by resection-arthrodesis]. / Tumeurs à cellules géantes de l'extrémité inférieure du radius traitées par résection-arthrodèse.

The distal end of the radius is one of the sites commonly affected by giant-cell tumor of bone; it poses problems of reconstruction after resection of the distal radius. The authors present a retrospective study of 5 giant cells tumors treated by resection-arthrodesis of the wrist. These tumors were seen in 3 men and 2 women. From the radiological point of view, all tumors were extensive and lytic lesions centered in the epiphysis and involving the metaphysis; the wrist joint was respected. From the histological point of view, the tumors were grade I in 3 cases and grade II in 2 cases. With a mean follow up of 8 years, the results were considered good in 3 cases, fair in 1 case and poor in 1 case. A high incidence of bone complications was noted: delayed union (up to 11 months) and fracture of the graft, which occurred in 3 patients.

Effect of hepatitis B virus on tumour necrosis factor (TNF alpha) gene expression in human THP-1 monocytic and Namalwa B-cell lines.

In response to viruses, monocytes and B cells produce TNF alpha. Therefore, we investigated TNF alpha gene expression and protein secretion in a human monocytic cell line, THP-1, and a Burkitt's lymphoma B-cell line, Namalwa, in response to hepatitis B virus (HBV). Stimulation by phorbol myristate acetate (PMA) (100 ng/ml for 48 h) induced TNF alpha secretion in THP-1 and Namalwa cells (100 to 300 pg/ml). In THP cells, the optimum response (> 2000 pg/ml) was obtained in the presence of a second mitogenic signal such as lipopolysaccharide (LPS) (10 microg/ml for 24 h). In our activation conditions, Northern blot analysis revealed a marked accumulation of TNF alpha mRNA species at 1.7 kb in both cell lines. When PMA- or PMA+LPS-stimulated THP-1 cells were exposed to HBV, TNF alpha protein and mRNA significantly decreased (> 50%). In contrast, HBV exposure of PMA-activated Namalwa cells resulted in strongly increased TNF alpha protein secretion (1 ng/ml). In this case, HBV induced TNF alpha mRNA accumulation that consisted of two types: a regular 1.7 kb and two novel high molecular weight (HMW) species at 3.7 and 4.3 kb. Exposure of stimulated THP-1 and Namalwa cells to HBV resulted in HBs and pre-S1 antigen production in the supernatants. In addition, HMW HBV DNA forms were detected in both cell lines, but with distinct HindIII restriction patterns. These findings indicate that TNF alpha gene expression may be differently regulated by HBV in activated human macrophages and B cells, and thus TNF alpha may be involved in the pathogenesis of HBV.

Identification of the B cell superantigen-binding site of HIV-1 gp120.

Previous studies showed that the gp120 envelope protein of HIV-1 is able to crosslink membrane IgM on normal human B cells and to induce their activation in a V(H)3 immunoglobulin gene-family-specific manner. Because this V(H) gene family is the largest in the human repertoire, this superantigen (SAg) property is thought to have deleterious consequences for the host, including a progressive decline of B cells with progression of the HIV-1-induced disease. Here, we have identified the sequence motifs on gp120 involved in SAg binding to normal Igs. We show that this SAg-binding activity is present in gp120s from highly divergent isolates of HIV-1 belonging to clades derived from various geographical origins, and that carbohydrate residues are not essential for its expression. The SAg-binding site is formed by protein sequences from two regions of the gp120 molecule. The core motif is a discontinuous epitope spanning the V4 variable domain and the amino-terminal region flanking the C4 constant domain. The most critical residues appear to be Leu395-Asp397 and Ile425-Gln427. Residues from the C2 constant domain (positions 252-272) also seem to play an accessory role in SAg binding of gp120 to normal human Igs. These findings are important in the design of a successful gp120-based vaccine against HIV-1.

[Intramuscular myxoma. Apropos of two cases]. / Myxome intra-musculaire. Apropos de deux localisations.

The authors report two cases of rare localization of intra muscular myxoma: one in the buttock, and the other in the lumbar area. The first case, a 58 years old woman had a four month history of a mass in the buttock. Computed tomography revealed the presence of a solid tumor. Diagnosis was based on histological examination. After surgical treatment no recurrence was observed after fourteen months. The second case was a 54 years old woman who presented a sciatica with back pain and neurological signs. The symptoms didn't response to medical treatment. Computed tomography showed an enlarged and-cystic lumbar lesion extending to the first sacral hole, with bone erosion of L3 and L4 articular apophysis and spinous process. Needle biopsy and surgical excision of the tumor were performed. Total neurological recovery was observed and no recurrence was observed after three years. The authors reminded the characteristics of this rare and benign soft tissue tumor and specified the place of magnetic resonance imaging (MRI) to establish the diagnosis which was still confirmed by histological examination of an open biopsy. Clinical follow-up revealed exceptional recurrence and no metastasis.