BCR-ABL-mediated upregulation of PRAME is responsible for knocking down TRAIL in CML patients.

Tumor necrosis factor-related apoptosis-inducing ligand-TNFSF10 (TRAIL), a member of the TNF-α family and a death receptor ligand, was shown to selectively kill tumor cells. Not surprisingly, TRAIL is downregulated in a variety of tumor cells, including BCR-ABL-positive leukemia. Although we know much about the molecular basis of TRAIL-mediated cell killing, the mechanism responsible for TRAIL inhibition in tumors remains elusive because (a) TRAIL can be regulated by retinoic acid (RA); (b) the tumor antigen preferentially expressed antigen of melanoma (PRAME) was shown to inhibit transcription of RA receptor target genes through the polycomb protein, enhancer of zeste homolog 2 (EZH2); and (c) we have found that TRAIL is inversely correlated with BCR-ABL in chronic myeloid leukemia (CML) patients. Thus, we decided to investigate the association of PRAME, EZH2 and TRAIL in BCR-ABL-positive leukemia. Here, we demonstrate that PRAME, but not EZH2, is upregulated in BCR-ABL cells and is associated with the progression of disease in CML patients. There is a positive correlation between PRAME and BCR-ABL and an inverse correlation between PRAME and TRAIL in these patients. Importantly, knocking down PRAME or EZH2 by RNA interference in a BCR-ABL-positive cell line restores TRAIL expression. Moreover, there is an enrichment of EZH2 binding on the promoter region of TRAIL in a CML cell line. This binding is lost after PRAME knockdown. Finally, knocking down PRAME or EZH2, and consequently induction of TRAIL expression, enhances Imatinib sensibility. Taken together, our data reveal a novel regulatory mechanism responsible for lowering TRAIL expression and provide the basis of alternative targets for combined therapeutic strategies for CML.

The relative influence of the topography and chemistry of TiAl6V4 surfaces on osteoblastic cell behaviour.

Proliferation and adhesion of mouse (MC3T3-E1) osteoblastic cells and primary human osteoblastic cells were carried out on Ti6Al4V titanium alloy samples with varied surface roughnesses. Mechanically or manually polished surfaces were prepared to produce respectively non-oriented or oriented residual polishing grooves. Sand-blasted surfaces were prepared using 500 microm or 3 mm alumina particles. Surface roughness parameters showed a negative correlation in comparison to proliferation and adhesion parameters. X-ray microprobe chemical surface microanalysis showed complete disturbance of the surface element composition of the Ti6Al4V alloy following sand-blasting treatment. An AlOx-enriched layer was observed on sample surfaces. This may lead to the suspicion that the concomittant effect of surface roughness amplitude and AlOx surface concentration has an effect on osteoblastic cell proliferation and adhesion. These findings show the significance of chemical surface analysis after any surface treatment of titanium-based implants before any biological use.

[Pseudotumor manifestation of metallosis in a hip prosthesis]. / Manifestation pseudo-tumorale d'une métallose sur prothèse de hanche--à propos d'un cas.

A pseudo-tumour due to metallosis is described in association with an iso-elastic hip replacement. This is a relatively rare lesion which may be difficult to diagnose. Scintigraphy and radiography may be helpful in distinguishing the lesion from a primary or secondary neoplasm, but the presence of osteolysis adjacent to the prosthesis will suggest the true nature of the lesion.

[Tibiotarsal arthrodesis: value of external fixator associated with in situ cancellous bone graft. Initial results apropos of 18 cases]. / L'arthrodèse tibio-tarsienne: intrêt du fixateur externe associé à une greffe osseuse fragmentée in situ. Résultats préliminaires à propos de 18 cas.

Tibio-talar arthrodesis poses some problems and the most frequent are non-union and varus malalignment of the ankle joint. The aim of this report was to present a new technique of ankle joint arthrodesis. The principles of this procedure are as follows: firstly, the external fixation (A.L.J.) is framed, secondly, perpendicular cuts are made in the tibial plafond and talus through an anterior longitudinal approach; and thirdly, the gap is filled with cancellous bone graft which is taken preferably on the iliac crest. If the back-foot is not correctly lined up preoperatively, the external device is framed in two steps: the first step consists in putting the pins. Then perpendicular cuts are made, and the back-foot is correctly lined up using calcaneal pins. The second step consists in connecting tibial pins and foot pins using union-rods. The last step of the procedure is to fill the gap with cancellous bone graft. The external fixation device is removed after 45 days and a shortleg walking cast is put for 45 days. Between 1981 and 1992, 18 arthrodesis were performed on various diagnosis: 9 post-traumatic tibio-talar osteoarthritis, 4 residual neurologic diseases, 2 rheumatoid arthritis and 3 recent post-traumatic lesions. There were 17 patients (one bilateral case), 4 females and 13 males; the middle age at the time of operation was 44.5 years (20 to 60) and there were 10 right ankles and 8 left. The tibio-talar arthrodesis was performed alone in 14 cases, but it was associated with a talo-calcaneus arthrodesis in 4 cases. The after care was without complications except 3 pins infection which cured with antibiotics. All the cases had a good bony union within 3 to 6 months and the orientation of the backfoot was always satisfactory without varus malalignment. All the patients could put one's shoes without having recourse to orthopaedic shoes. In conclusion, this operative procedure seems to minimize the problems and pittfalls of the ankle arthrodesis.

Medium-term results of 173 ligamentoplasties of the anterior cruciate ligament using the MacIntosh technique reinforced by the Kennedy ligament augmentation device (LAD).

This is a retrospective study of 173 cases of chronic laxity of the knee, surgically treated between May 1985 and December 1988 using the MacIntosh technique (quadriceps-plasty) reinforced with the Kennedy ligament augmentation device (LAD). It involved 171 operations, 113 men and 58 women aged between 15 and 49 years (average 26 years), the majority of whom were active in sports both at competition (51 cases) and at recreational level (119 cases). There were 101 lesions of the medial meniscus (58.4%) and 94 lesions of the lateral meniscus (54.4%); only 41 knees had no meniscal lesion (23.6%). The results at medium term (between 4 and 8 years follow-up) were based on 107 cases (61.8%). The tolerance of the reinforcement was excellent as there were no instances of either acute or chronic synovitis in this series. The anatomical results evaluated using the Lachmann test (maximum manual Lachmann) showed no differential in 24 cases (22.8%), a differential of between 0 and 2 mm in 54 cases (50.5%), of between 2 and 4 mm in 20 cases (19%) and of > 4 mm in 9 cases (8.7%). The functional results evaluated using the Arpège CLAS system showed 83% of results to be satisfactory (score > 23). The radiological results showed that 63 knees (58.9%) had no subclinical or clinical signs of medial or lateral femorotibial osteoarthritis. In total, with an average follow-up of > 5 years (4-8 years), it was found that the MacIntosh quadriceps-plasty reinforced with the Kennedy LAD was not accompanied by any iatrogenic disease.(ABSTRACT TRUNCATED AT 250 WORDS)

[Anterior instability of the shoulder associated with fracture of the coracoid process. Apropos of 3 cases]. / L'instabilité antérieure de l'épaule associée à la fracture du processus coracoïde. A propos de trois cas.

PURPOSE OF THE STUDY: The aim of this paper is to present an unusual lesion associating anterior instability of the shoulder with a fracture of the horizontal part of the coracoid process. It emphasizes surgical treatment using the Latarjet procedure. MATERIAL AND METHODS: Three cases are presented: One case was a recurrent anterior dislocation of the shoulder associated with a fracture of the horizontal part of the coracoid process; an other case was a painful shoulder associated with pseudarthrosis of the coracoid process and a fracture of the anterior and inferior edge of the glenoid. In the last case there was a recurrent dislocation of the shoulder associated with a pseudarthrosis of the coracoid process detected intra-operatively. All the patients were operated on using the Latarjet's procedure using the fractured coracoid process. RESULTS: The three cases had a good result. DISCUSSION: The association of an anterior dislocation of the shoulder and a fracture of the coracoid process is very unusual. It is often unrecognized because of poor knowledge of this lesion or a poor quality of the radiograms performed in the emergency room. The most likely mechanism is a direct impact of the humeral head against the coracoid process during the dislocation. The fracture is located (as in our 3 cases) at the horizontal part of the coracoid process near its elbow and they are often associated lesions at the anterior and inferior edge of the glenoid. The diagnosis requires good quality radiograms and a Garth's view systematically performed after reducing the dislocation. When the shoulder is painful or unstable, surgical treatment is performed and the Latarjet's procedure takes care of the pseudarthrosis and the instability of the shoulder. CONCLUSION: Isolated fractures of the coracoid process are probably uncommon. When there is a fracture of the horizontal part of the coracoid process anterior instability of the shoulder should be suspected. This is the case when the shoulder has never been dislocated and when the standard radiograms are "normal" without "crossing lesions" at the anterior and inferior edge of the glenoid or at the humeral head (Hill-Sach lesion).

[Mid-term results of 173 cases of surgery of the anterior cruciate ligament using the Mac Intosh procedure, reinforced by the Kennedy Ligament Augmentation Device]. / Résultats à moyen terme de 173 plasties du ligament croisé antérieur selon la technique de Mac Intosh renforcée par Kennedy-Lad.

UNLABELLED: This is a retrospective study of 173 chronic laxities of the knee operated on between May 1985 and December 1988 using the Mac Intosh procedure, reinforced by the Kennedy L.A.D. Follow-up was between 4-8 years and the same surgeon operated on all the knees. MATERIALS AND METHODS: 171 patients were operated on (113 men and 58 women) aged between 15-49 years (average age 26.5 years). The vast majority were sportsmen both at competition level (51 cases) and at recreational level (119 cases). The average time-span between accident and intervention was 15 months (1-240 months). In the pre-operative assessment, 80 cases (46.2 per cent) were found to have a grade II Lachman test and 91 cases (52.6 per cent), a grade III Lachman test; a positive pivot shift was found in more than 95 per cent of cases. There were lesions of the medial meniscus in 101 cases (58.4 per cent), of the lateral meniscus in 94 cases (54.4 per cent) and there was no meniscal lesion in only 41 cases (23.8 per cent). Finally there were 22 chondral lesions of the medial femoral condyle (12.7 per cent) and 7 of the lateral condyle (4.1 per cent). RESULTS: These were based on 159 cases (14 lost to follow-up before the third post-operative month), but only 107 (61.8 per cent) were reviewed by one of us (i.e. not the original surgeon). Tolerance of the L.A.D. was excellent. There was no sign of synovitis or joint effusion persisting beyond 1 year. Furthermore, there were no serious complications (no sepsis, only 4 cases (2.3 per cent) of joint stiffness, 2 cases of reflex sympathetic dystrophy and 5 cases of sural phlebitis (2.9 per cent). Moreover, the few minor complications that arose resolved with the appropriate treatment. Anatomical results, evaluated using. Lachmans test (maximum manual Lachman measured with the Bercovy Laximeter) showed 24 cases (22.4 per cent) with zero differential residual laxity, 54 cases (50.5 per cent) with a differential laxity of between 0-2 mm; 20 cases (18.7 per cent) with a laxity of between 2-4 mm and in 9 cases (8.4 per cent) a laxity of greater than 4 mm. Functional results, using the Arpège C.L.A.S. system showed good results in 83 per cent (score > and unsatisfactory results in 17 per cent of cases. The long time-span between intervention and subsequent review with the C.L.A.S. system should be taken into account. However, the proportion of competitive sportsmen to recreational sportsmen was practically identical when comparing pre-traumatic figures (C = 29.5 per cent, R = 68.8 per cent) to figures at the time of follow-up (C = 21 per cent, R = 69.5 per cent). Radiological results (A.P. and Schuss films) showed 63 knees (58.9%) with no signs of either medial or lateral, preliminary or full-blown, femoro-tibial osteo-arthritis. DISCUSSION: With an average follow-up of > 5 years (4-8 years), it is possible to say that ligamentoplasty of the anterior cruciate ligament using the Mac Intosh procedure reinforced with the Kennedy L.A.D. is not causative of any iatrogenic problems. The anatomical results were totally satisfactory (almost normal) in 72.9 per cent of cases; the radiological results showed ""normal'' knees in 58.9 per cent of cases and functional results were identical to results obtained using many other techniques.

[Arthroscopic meniscectomy. Comparison of the functional results of meniscectomy in patients above and under 45 years of age. Apropos of 107 cases]. / La méniscectomie arthroscopique. Résultats fonctionnels comparés des méniscectomies avant et après 45 ans. A propos de 107 cas.

A comparative retrospective study of 107 cases of arthroscopic meniscectomies performed between December 1985 and December 1988 on 52 operated patients under 45 (P1 = 54 knees) and 52 operated patients over 45 (P2 = 53 knees). Those two populations have been selected among 292 isolated meniscal lesions files (without anterior cruciate ligament tear) operated for arthroscopic meniscectomy between 1985 and 1988. There were 81 medial meniscus lesions, 16 lateral meniscus lesions and 10 bi-meniscal lesions. The follow-up was for 1 to 5 years with a score of 70.3 per cent functional satisfactory results for the above 45 years (P2) and a score of 89.4 per cent below 45 (P1). Regarding the medial meniscus lesions only, we count 76 per cent (P2) satisfactory results versus 87.5 per cent (P1). This assessment can be easily explained by the variety of meniscal lesions (8 degenerative meniscal lesions among P2 namely 15 per cent), by associated cartilage lesions of the medial compartment of the knee (medial condyle: P2 = 37.75 per cent, medial tibial plateau: P2 = 41.5 per cent) and by genu varum deformity. However, in spite of this significant statistical difference (alpha < 0.05), we don't think we should condemn the arthroscopic meniscectomy over 45: the morbidity is very low and if some patients were not cured, the majority of them said that they improved after the operation. The cartilaginous degenerations of the medial compartment, discovered during arthroscopy, in a context of genu varum, don't need any tibial osteotomy at first, especially if they are asymptomatic and without tibia varum.