EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts.

The genes involved in the t(12;22)(q13;q12) translocation found recurrently in malignant melanoma of soft parts have been characterized and shown to form, in four cases studied, hybrid transcripts. The deduced chimaeric protein encoded by the der(22) chromosome consists of the N-terminal domain of EWS linked to the bZIP domain of ATF-1, a transcription factor which may normally be regulated by cAMP. ATF-1 has not previously been implicated in oncogenesis. EWS was first identified as forming a hybrid transcript in Ewing's sarcoma, which links its N-terminal domain to the DNA binding domain of the FLI-1 gene. Thus the oncogenic conversion of EWS follows a common scheme of activation, exchanging its putative RNA binding domain with different DNA binding domains that appear to be tumour-specific.

DNA-binding and transcriptional activation properties of the EWS-FLI-1 fusion protein resulting from the t(11;22) translocation in Ewing sarcoma.

The 5' half of the EWS gene has recently been described to be fused to the 3' regions of genes encoding the DNA-binding domain of several transcriptional regulators, including ATF1, FLI-1, and ERG, in several human tumors. The most frequent occurrence of this situation results from the t(11;22)(q24;q12) chromosome translocation specific for Ewing sarcoma (ES) and related tumors which joins EWS sequences to the 3' half of FLI-1, which encodes a member of the Ets family of transcriptional regulators. We show here that this chimeric gene encodes an EWS-FLI-1 nuclear protein which binds DNA with the same sequence specificity as the wild-type parental FLI-1 protein. We further show that EWS-FLI-1 is an efficient sequence-specific transcriptional activator of model promoters containing FLI-1 (Ets)-binding sites, a property which is strictly dependent on the presence of its EWS domain. Comparison of the properties of the N-terminal activation domain of FLI-1 to those of the EWS domain of the fusion protein indicates that EWS-FLI-1 has altered transcriptional activation properties compared with FLI-1. These results suggest that EWS-FLI-1 contributes to the transformed phenotype of ES tumor cells by inducing the deregulated and/or unscheduled activation of genes normally responsive to FLI-1 or to other close members of the Ets family. ES and related tumors are characterized by an elevated level of c-myc expression. We show that EWS-FLI-1 is a transactivator of the c-myc promoter, suggesting that upregulation of c-myc expression is under control of EWS-FLI-1.

Detection of plasma tumor DNA in head and neck squamous cell carcinoma by microsatellite typing and p53 mutation analysis.

Recent arguments have suggested that tumor DNA in cancer patients could be found in plasma, but different points remain unclear. Using a series of 117 head and neck squamous cell carcinoma tumors, our goals for this study were: (a) to quantify the amount of plasma DNA; (b) to evaluate the presence of plasma tumor DNA; and (c) to analyze the clinical relevance of tests based on plasma DNA analyses. Low levels of plasma DNA were found in most samples, but all were successfully amplified. Two different methods were used to detect tumor-specific genetic alterations: (a) microsatellite instability at UT5085 with an established sensitivity of 1:500; and (b) p53 mutation screening. Of the 117 tumors typed at UT5085, 65 demonstrated bandshifts (55%). Plasma and tumor DNA a showed similar alteration in only one case among these samples, and the prevalence of tumor DNA in plasma was estimated to be <2% using microsatellite analysis. Tumor DNA was detected in plasma at a higher prevalence (2 of 11 cases) when using p53 mutant allele-specific amplification. These results showed that in plasma, tumor DNA is largely diluted by normal DNA. By comparison with previously published studies, the prevalence of microsatellite alterations in plasma in this series of head and neck squamous cell carcinomas is very low, despite the fact that a large series of tumors was analyzed. To explain this discrepancy, we analyzed the possibility of PCR artifacts as suspected by the presence of loss of heterozygosity in two plasma DNA samples without a similar tumor DNA alteration. When DNA concentrations were under the threshold of detection (<100 ng/ml), we demonstrated that PCR artifacts could occur at random, and, if misinterpreted, these false genetic alterations could artificially enhance the frequency of plasma DNA alterations. This may have been suspected in previously published series, but it has never been discussed before. Microsatellite analysis on plasma DNA is difficult to interpret and can frequently be misleading. Plasma DNA should be analyzed with very sensitive and specific methods such as mutant allele-specific amplification, which excludes artifacts but requires specific optimization that is probably not compatible with routine and clinical use.

Prevention of postoperative venous thrombosis: a randomized trial comparing unfractionated heparin with low molecular weight heparin in patients undergoing total hip replacement.

A double blind randomized trial comparing subcutaneous enoxaparin (40 mg once daily) with standard unfractionated calcium heparin administered at a dose of 5,000 units every 8 hours in patients undergoing elective hip replacement has been performed. Treatment regimens began 12 hours preoperatively with enoxaparin, 2 hours preoperatively with standard unfractionated calcium heparin, and were continued for 15 days or until discharge. Venography was performed in all patients. Two hundred thirty-seven patients were included in the study: 113 received unfractionated heparin and 124 received enoxaparin. The incidence of proximal deep vein thrombosis was reduced from 18.5% in the unfractionated heparin group to 7.5% in the enoxaparin group (p = 0.014), and the incidence of total deep vein thrombosis was similarly reduced from 25% to 12.5% (p = 0.03). There were two major bleeding episodes and one minor bleed in the enoxaparin group compared to two minor bleeds in the unfractionated heparin group. Patients who received enoxaparin required fewer red blood cell transfusions and had a significantly higher hemoglobin on postoperative days 3 and 4. Thus prophylaxis with enoxaparin, 40 mg once daily, is simple, safe and more effective than standard low dose unfractionated heparin in preventing deep vein thrombosis in patients undergoing elective hip replacement.

Interphase molecular cytogenetics of Ewing's sarcoma and peripheral neuroepithelioma t(11;22) with flanking and overlapping cosmid probes.

The translocation, t(11;22)(q24;q12), recurrently observed in Ewing's sarcoma and in peripheral neuroepithelioma has been recently cloned. The analysis of a series of ES/PNE has revealed that the chromosome 22 breakpoints are clustered in a small region of 7 kb, called EWSR1, and that those on chromosome 11 are spread over a larger region of 40-50 kb, called EWSR2. Cosmids from loci flanking or overlapping these two regions have been obtained. We demonstrate here that fluorescence in situ hybridization (FISH) with these cosmids allows the localization of the two breakpoints with a 10-kb resolution and leads to a rapid and reliable ES/PNE diagnosis.

[Use of an isolator (so-called "bubble") in orthopaedic surgery (author's transl)]. / Utilisation de la bulle en chirurgie orthopédique.

The results of 2 series of casualties presenting with femoral neck fractures and operated with Moore prostheses are compared. The first was operated between September 18, 1972 and July 17, 1975 in a conventional way; the other between July 18, 1975 and January 10, 1977 under an Isolator. The rate of infection was much reduced in the latter. It seems to indicate the important function of this apparatus in the prevention of postoperative infection.

[Secondary nailing of the tibia in non-unions with septic risk. Indications and results]. / Enclouage secondaire du tibia dans les défauts de consolidation "à risque septique". Indications et résultats.

Reamed or unreamed intramedullary nailing with or without associated grafting are well established technics for treating tibial non-unions. However, certain cases can present an increased risk of septic complications. The authors propose a classification of these risks into 4 grades based on a review of 25 cases: grade I (14 cases): non-union following open fractures with no history of infection; grade II (5 cases): non-union following fractures treated initially by external fixation; grade III (4 cases): non-union following septic fractures showing no current signs of active infection; grade IV (2 cases): septic non-union. The risks of intramedullary tibial nailing are evaluated. Only one case presented a serious septic complication leading to nail removal and knee arthrodesis. Intramedullary nailing may be indicated in grade I and II non-unions, but should rarely be used in grades III and IV.

[Treatment of recurrent luxation of total hip prosthesis by posterior methyl methacrylate buttress]. / Traitement des luxations récidivantes de prothèses totales de hanche par butée postérieure en méthacrylate de méthyle.

A shelf operation using cement held by screws inserted into the posterior wall of the acetabulum is described in cases of recurrent dislocation of hip prostheses. The procedure was used in 7 cases of total prostheses and 2 of femoral prostheses. The technique is simple and reliable. It should be used when there is no obvious malposition of the prosthesis or in the elderly when a further operation to re-orientate a faulty prosthesis would be too risky. The results were satisfactory with 7 successes in 9 patients.

[A case of bone lipoma of the femur head]. / Un cas de lipome intra-osseux de l'extrémité supérieure du fémur.

A case of intra-osseous lipoma of the upper femur is reported. A review of the literature shows that this lesion is rare, only about 33 cases having been published. The radiological appearance is that of a fibroma. The diagnosis is made at the time of surgery which reveals the presence of fat in a large cavity. Curettage and bone graft resulted in healing.

[Recurrent traumatic posterior luxation of the hip with defect of the sphericity of the femoral head. Value of x-ray computed tomography]. / Luxation traumatique récidivante postérieure de la hanche avec défaut de sphéricité de la tête fémorale. Intérêt de la tomodensitométrie.

The authors report a case of traumatic recurrent posterior dislocation of the hip. The cause of the recurrence was related to flattening of the femoral head on its anterior aspect with incongruity between the head and the anterior wall of the acetabulum. The diagnosis was made by tomodensitometry.

[X-ray computed tomography in the study of fractures of the calcaneus]. / Apport de la tomodensitométrie dans l'étude des fractures du calcanéum.

In a series of 28 calcaneal fractures, computed tomography scanning has shown axial deformities in the coronal and horizontal (plantar) planes not previously recognized. Two-thirds of the fractures investigated showed a deformity in at least two planes. A combination of dorsiflexion, valgus and adduction was present in one-third of the cases. This examination allowed a precise measure to be made of the enlargement of the calcaneus which very frequently occurs and was greater than 25 per cent in two-thirds of the cases. It makes it possible to visualize subtalar and calcaneocuboid incongruence with great precision and, in particular, to determine the size of the incongruous surface and its severity. Computed tomography scanning showed the existence of subtalar incongruity without depression of the thalamus, which is a concept which is not well recognized. It shows incongruity which is not evident on normal radiographs or, conversely, which may be falsely interpreted from deceptive pictures. The results of this study indicate that the usual classifications based on radiological examination are inadequate and need to be revised. The accuracy of this examination leads to the hope of more precise indications for treatment in the future.

[Mixed fractures of the posterior wall of the acetabulum. Value of x-ray computed tomography]. / Fractures mixtes de la paroi postérieure du cotyle. Intérêt de la tomodensitométrie.

The authors have studied three cases of fracture of the posterior wall of the acetabulum in which one fragment was separated and another was impacted. The nature of the lesions were not able to be appreciated on standard radiographs but was visualised by means of tomodensitometric studies. The patients were treated surgically to obtain an accurate reconstruction of the articular surface. The importance of tomodensitometry in the diagnosis of such lesions is stressed.

[Knee arthrodesis using tibio-femoral rods following ablation of the septic total prosthesis]. / Arthrodèse du genou par tiges tibio-fémorales après ablation de prothèses totales septiques.

A technique of knee arthrodesis is described, using a fixation by medullary tibio-femoral rods introduced in the supra-malleolar region of the tibia. This procedure has been used with success as a salvage procedure after removal of four septic total prostheses of the knee. It allowed an early weight bearing and was indicated in cases where external fixator had failed or was contra-indicated.

[Mycobacterium fortuitum infection after total hip prosthesis. A report of 3 cases (author's transl)]. / Suppurations à mycobacterium fortuitum après prothèse totale de hanche. A propos de 3 cas.

The authors have observed three instances of sepsis due to Mycobacterium fortuitum complicating total hip replacement for osteoarthritis. The case histories are fully described. The requirements are given for recognition of the organism which grows on special culture media and which may be mistaken for Mycobacterium tuberculosis. This feature explains why, in some cases, the organism may not be discovered. Antibiotics were ineffective but the general condition of the patient was not greatly affected.

[Treatment of bimalleolar fractures by centromedullary nailing of the fibula]. / Traitement des fractures bimalléolaires par enclouage centro-médullaire du péroné.

An osteosynthesis technique involving nailing of the fibula was used to treat 106 bimalleolar fractures. Details of the technique used are described and results analyzed with respect to clinical course and radiologic findings. A generally favorable outcome was obtained. Nailing of the fibula provides a solid foundation, particularly in low and comminuted fractures.