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P Djian

Publications and source records attributed to P Djian.

At least 19 recordsLinked to original sources

[Osteochondritis dissecans of the femoral condyles: report of 892 cases].

PURPOSE OF THE STUDY: Osteochondritis rarely involves the femoral condyles. Discovery in this localization raises several questions concerning the nature of the articular cartilage, the potential for spontaneous healing, and, in the event of a free fragment, the outcome after its loss or repair. MATERIAL AND METHODS: This multicentric study included 892 pediatric and adult cases, the cutoff between two series being defined by fusion of the inferior growth plate. We excluded medical or surgical osteochondritis, cases involving the patella, osteochondral fractures, juvenile polyosteochondrosis, adult osteonecrosis, and osteochondritis beginning after the age of 50 years. RESULTS: Mean age at diagnosis was 16.5 years. Mean age at treatment onset was 22 years. Pain was the predominant symptom. 80% of cases were unilateral and 70% involved the medial condyle. The anatomic lesions were different in adults, showing more advanced degradation. At diagnosis, Bedouelle stages Ia and IIb constituted 80% of the cases observed among children while in adults, 66% were Bedouelle stages IIb to IV. Outcome was very good for the majority of children with Hughston clinical stage 4 while half of the x-rays were Hughston stage 3 and 4. There were thus a large percentage of children with abnormal xrays whose disease history was not yet terminated. In the adult series, the percentages of Hughston 3 and 4 was about the same as clinically. The x-rays were rarely perfectly normal since half of the clinical stage 3 patients were noted in stage 4. An abnormal x-ray with a very good clinical presentation was observed in a very large proportion of patients. DISCUSSION: It is difficult to interpret the plain x-ray and identify patients with a potentially unfavorable prognosis. We defined three radiographic classes: defect, nodule and empty notch. The Bedouelle classification uses information from all available explorations, particularly MRI and arthroscopy. Numerous therapeutic methods are used. Interruption of sports activities is the first intention treatment for children. Data in the literature and the findings of this symposium do not demonstrate any beneficial effect of immobilization on healing compared with simple abstention from sports activities. Transchondral perforation is a simple operation with low morbidity. In 85% of cases, it was used for lesions with an intact joint cartilage considered stable in 96% of cases. Healing was achieved in six months for 48% if the growth plate had not fused. The fragment was fixed in 43% of the cases with a loose cartilage fragment. Outcome was fair but degraded with the state of the joint cartilage and thus the stability of the fragment. Fixation must stabilize the fragment but not prevent further consolidation via osteogenesis. This is why deep perforations are drilled beyond the ossified area and additional osteochondral grafts are used. The Wagner operation gives less satisfactory results than more complicated procedures. Removal of a sequestrum is a simple, minimally invasive procedure with an uneventful postoperative period, but in the long term it favors osteoarthritic degradation, especially when performed in adults. Mosaic grafts give good mid term results. Morbidity is low especially if the grafts are harvested above the notch. The question of chondrolysis around the grafts was beyond the scope of this study. Chondrocyte grafting is difficult to accomplish and is expensive. The mid term results are good for large lesions. Osteotomy is logical only in the event of early stage osteoarthritic degradation. DECISION ALGORITHM IN CHILDREN AND ADOLESCENTS: If the plain x-ray reveals a defect (class I), simple interruption of sports activities should be proposed. Two situations can then develop. First, in a certain number of patients, the pain disappears as the defective zone ossifies progressively. Complete cure is frequent before the age of 12 years. In the second situation, the knee remains painful and the x-ray does not change or worsens to a class II nodular formation. In this case an MRI must be obtained to determine whether the joint cartilage is normal. There are two possibilities. First, the osteochondral fragment is viable and most probably will become completely re-integrated, particularly if the lesion is far from the growth plate. Necrosis is the other possibility. Transchondral perforations are needed in this case. If on the contrary the cartilage is altered, there is little hope for spontaneous cure. Arthroscopy may be needed to complete the exploration. Fragments, especially if there is a large surface area, must be fixed. Perforations to favor revascularization are certainly useful here. In the last situation (class III), the fragment wobbles on a thin attachment or has already fallen into the joint space. This is the type of problem generally observed in adults. The decision algorithm in adults is the same as in children for the rare nodular aspects (class II). There could be a discussion between transcartilage perforation and fixation. If there are a large number of fragments, fixation may not be fully successful and the lesion might be considered class III. For class III lesions, three operations can be used: removal of the sequestrum, mosaic bone-cartilage grafts, or autologous chondrocyte grafts. At the same follow-up, mosaic grafts give better results than excision of sequestra. It may be useful to remove sequestra in a limited number of situations: if there is just a small area of osteochondritis, the lesion is old and partially healed, or the zone is non weight-bearing. For other lesions, we favor mosaic grafts. We still do not have enough follow-up to assess the long-term outcome with these mosaic grafts, but simple excision clearly favors osteoarthritic degradation. Can chondrocytes grafts be compared with mosaic grafts? Chondrocyte grafts have been used for very large lesions and have given results similar to mosaic grafts. It might also be possible to combine fixation of a loose fragment and a mosaic graft. LESSONS FROM THIS STUDY: 1) The prognosis of osteochondritis is better before than after fusion of the growth plate but the lesion does not always heal in children. 2) Presence of osteochondritis requires complementary anatomic and functional exploration to determine the stability and the vitality of the fragment. 3) Attention must be taken to perform transchondral perforations early enough, particularly in children. 4) Screw fixation is not always sufficient. The trophicity of the fragment and its blood supply must be improved. 5) Mosaic grafts are preferable to excision of the fragment. 6) Chondrocyte grafts will be more widely used in the future.

Adolescent↗

[Adult lateral meniscus].

Meniscal lesion does not mean meniscectomy and this is particularly true for the lateral meniscus. The reputation of mildness of the meniscectomy is usurped. The rate of joint space narrowing after lateral meniscectomy is of 40% at a follow-up of 13 years compared to 28% for the medial meniscus (symposium SFA 1996). Several arguments explain those results: biomechanical: the lateral meniscus contributes to the congruence; particularly the lateral meniscus is the zone where antero-posterior translational during knee flexion is 12 mm. The pejorative effects of lateral meniscectomy have conducted, more though to the medial meniscus, to the concept of meniscal economy. Lateral meniscectomy must be as partial as possible. Particularly, a discoid meniscus presenting a complete tear should be treated by a meniscoplasty in order to shape the meniscus in a more anatomic form than a total meniscectomy. Lateral meniscectomy is indicated in complex or horizontal cleavage, symptomatic, on stable knees. A particular case is the cyst of the lateral meniscus. It is a cystic subcutaneous formation, usual consequence of a horizontal cleaved meniscus of which the particularity is that it opens besides the articulation. The strategy must not consist in the isolated treatment of the cyst. This pathology should be addressed by an arthroscopic meniscectomy reaching the meniscosynovial junction at the level of the cyst. Meniscal repair must be proposed every time if possible. Criteria of reparability are better studied on MRI. Preoperatively MRI is the first choice radiological exam. Two essential indications can be held back: the vertical peripheral longitudinal lesion is on the non-vascularized area, and the horizontal cleaving of the junior athlete (if the cleaving remains purely intra meniscal). Meniscal repair is highly performed when the meniscal tear is associated to a rupture of the ACL (simultaneous reconstruction of the LCA). Postoperative outcome is different of that of a "simple" arthroscopic meniscectomy. The healing process being slow, it suits to protect the suture by a splint in the first month, and with an exclusion of sports with knee torsion during 6 months. Functional results (absence of secondary meniscectomy) and anatomical results (reality of the cicatrisation) are good in 77% of cases (symposium of the French Society of Arthroscopy 2003) at a follow-up of 55 months. Survivorship analysis indicates that majority of the failures occur within two years: this testifies a default of primary cicatrisation. At the studied follow-up, meniscal repair was efficient to protect the cartilage. Lateral meniscus results are better that medial meniscus one. Those data support indications: All suspicion of meniscal lesion must have an MRI preoperatively to confirm the lesion, to localize her and to search criteria of reparability; All vertical longitudinal peripheral lesions can and must be repaired especially in young patients and children; All horizontal cleaving of the junior athletes should be treated by open repair; surgical abstention must be proposed when the lesion is non symptomatic, or when lesion is limited and associated to an ACL tear (in that case isolated ACL reconstruction is proposed), or when clinical symptoms are minimal; Meniscectomy, always arthroscopic, is proposed for a symptomatic lesion in the avascular zone or for a deep horizontal cleavage or a complex tear; Tear of the discoid meniscus should be treated by meniscoplasty. A painful knee after lateral meniscectomy might be due to a too limited initial meniscectomy: an iterative meniscectomy may be indicated or lateral femorotibial arthritis, especially after subtotal or total meniscectomy. In this last case and after failure of usual medical treatment such as viscosupplementation surgery may be indicated. Osteotomy in order to unload the lateral femorotibial compartment gives a partial response as the shearing forces remain. This osteotomy is indicated only if the lower limb axis is normal or in valgus. Meniscal allograft is an option in young patients in grade I or II arthritis. Results are promising. Rene Verdonk's series show a survivorship analysis of 75% at 7 years. Early diagnosis of a postmeniscectomy syndrome before cartilaginous lesions occur is essential for an adapted treatment. In conclusion, lateral meniscectomy are less frequent than those of the medial meniscus but their prognosis is less favorable. They should be early diagnosed (MRI). Treatment options are various: abstention, meniscectomy, and repair. Painful post lateral meniscectomy syndrome may be treated by a new surgical option: meniscal allograft.

Cysts↗

[Not Available].

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Journal Article↗

[Not Available].

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Journal Article↗

["Isolated" injury of the posterior cruciate ligament. Surgical treatment of isolated posterior cruciate ligament tears: a multicentric retrospective study of 103 patients].

PURPOSE OF THE STUDY: We present a retrospective multicentric series of carefully selected patients presenting "isolated" laxity of the posterior cruciate ligament. MATERIAL AND METHODS: The series included 103 patients who were reviewed clinically (with a dedicated review chart) and radiographically with measurement of posterior laxity (Telos 15 kg). RESULTS: In these patients with an isolated injury of the PCL (without associated injury of the peripheral ligament) DISCUSSION: The short follow-up of this series (four years) does not enable an assessment of the risk or benefit of PCL ligamentoplasty for arthrosic knees.

English Abstract↗

[Anterior cruciate ligament reconstruction: biomechanical comparison on cadaver specimens using a single or double hamstring technique].

PURPOSE OF THE STUDY: We worked with cadaver specimens to evaluate control of anterior knee laxity after reconstruction of the anterior cruciate ligament (ACL) comparing double two-strand anterolateral and posteromedial reconstruction with the classical four-strand technique. We hypothesized that the double reconstruction would provide better control of anterior laxity in both flexion and extension. MATERIAL AND METHODS: Sixteen cadaver knees were randomly assigned to reconstruction technique. Anterior tibial translation was measured with an arthrometer (Rolimeter) at maximal manual tension at 20 degrees, 60 degrees and 90 degrees flexion on the intact knee, after section of the ACL and after arthroscopic reconstruction using either the classical four-strand hamstring technique or a double two-strand anteromedial and posterolateral technique. An EndoButtonCL was used for the femoral fixation and a interference screw with staples for the tibial fixation. Variation in the length of each construct was measured between 0 degrees and 90 degrees flexion. RESULTS: In the single reconstruction group, the length of the graft varied by 0.5 +/- 0.7 mm between 0 degrees and 90 degrees flexion. In the double reconstruction group, the length varied by 0.5 +/- 0.9 mm for the anteromedial construct and 3.4 +/- 0.5 mm for the posterolateral construct. When studied with an intact ACL, anterior laxity of the 16 knees was 3.2 +/- 1.1, 3.5 +/- 1.5 and 2.6 +/- 1.1 mm at 20 degrees, 60 degrees, and 90 degrees respectively. After section of the ACL, laxity increased significantly at all angles: 9.4 +/- 3.3, 6.1 +/- 2.5 and 6.8 +/- 2.9 at 20 degrees, 60 degrees, and 90 degrees respectively. After classical four-strand single graft reconstruction, the residual anterior laxity was 3.7 +/- 0.9, 3.1 +/- 1.1, and 2.3 +/- 1.6 mm at 20 degrees, 60 degrees, and 90 degrees flexion. Statistical analysis using parametric or non-parametric tests as appropriate showed a significant difference in laxity at 20 degrees, 60 degrees, and 90 degrees of flexion between knees with a cut ACL and knees with reconstructed ACL. At 20 degrees flexion, residual laxity was greater after single-construct reconstruction. At 60 degrees and 90 degrees there was no significant difference in anterior translation of the tibia in knees with intact or reconstructed ACL. After reconstruction with the dual-construct technique, laxity was 3.4 +/- 1.3, 2.6 +/- 1.5, and 2.4 +/- 1.2 mm at 20 degrees, 60 degrees and 90 degrees flexion respectively. Laxity was significantly greater with a cut ACL than after reconstruction at 20 degrees, 60 degrees, and 90 degrees flexion, but there was no significant difference in anterior translation of the tibia at 20 degrees, 60 degrees, and 90 degrees flexion between knees with an intact and a reconstructed ACL. DISCUSSION: These results based on a clinical evaluation measuring anterior translation of the tibia with an arthrometer are in agreement with results in the literature using robots. Compared with the classical technique, reconstruction of the ACL with a dual-construct technique provides a statistically significant improvement in control of anterior tibial translation at 20 degrees of flexion. The advantage of the dual anteromedial and posteriolateral construct technique is thus not found in the control of anterior laxity but rather in control of rotation laxity. CONCLUSION: Reconstruction of the ACL with a two-bundle graft technique provides control of anterior laxity at 20 degrees, 60 degrees, and 90 degrees flexion similar to that observed in knees with an intact ACL while the single construct technique re-establishes physiological laxity at 60 degrees and 90 degrees only. This improved control of anterior laxity with the two-bundle reconstruction is a small improvement regarding anterior laxity, the more potential advantage concerning rotational stability.

Aged↗

[Reliability of the KT-1000 arthrometer (Medmetric) for measuring anterior knee laxity: comparison with Telos in 147 knees].

PURPOSE OF THE STUDY: The purpose of this study was to compare the reliability and the reproducibility of both the KT-1000 arthrometer (Medmetric) and Telos for measuring anterior knee laxity. The Telos was used as the reference technique. MATERIAL AND METHODS: Criteria for inclusion were preoperative anterior knee laxity, normal contralateral knee, and intra-articular surgery to reconstruct the anterior cruciate ligament. Between January 1st, 2000 and October 31st, 2001, 147 patients were operated on for knee instability using an autograft (BPTB or hamstring tendons). For each patient, comparative measurements were made for both knees preoperatively and postoperatively with an average follow-up of 16 months. Measurements with the KT-1000 apparatus were made with forces of 67 N, 89 N, 134 N and manual maximal force. For the Telos, a force of 250 N was used as recommended by the manufacturer. We also evaluated intraobserver variation between the two devices. RESULTS: The anterior translation preoperatively as measured by the KT-1000 at 89N was 4.2 +/- 2.4 mm and 6.3 +/- 2.5 mm at maximal manual force. The result for Telos was 3.0 +/- 3.6 mm. The data scatter obtained with Telos was wider than with KT-1000 (p<0.03). The sensitivity of Telos was 72% with 28% false negatives. With KT-1000, sensitivity increased as tensile force increased. Sensitivity was 65% at 89N, 73% at 134N and 92% at maximal manual force. The concordance between the KT1000 and Telos data was low for either preoperative (10%) or postoperative (30%) measurements. DISCUSSION AND CONCLUSION: In this study, the results of sensitivity and reproducibility as well as the minimal scatter of the values demonstrated the reliability of KT-1000 for measuring anterior translation of the knee. We recommend routine use of the KT-1000 device for measuring knee laxity. The low sensitivity and the high rate of false negative observed with Telos raises the question of its use a reference technique.

Adolescent↗

Oligomeric and polymeric aggregates formed by proteins containing expanded polyglutamine.

Neurological diseases resulting from proteins containing expanded polyglutamine (polyQ) are characteristically associated with insoluble neuronal inclusions, usually intranuclear, and neuronal death. We describe here oligomeric and polymeric aggregates formed in cells by expanded polyQ. These aggregates are not dissociated by concentrated formic acid, an extremely effective solvent for otherwise insoluble proteins. Perinuclear inclusions formed in cultured cells by expanded polyQ can be completely dissolved in concentrated formic acid, but a soluble protein oligomer containing the expanded polyQ and released by the formic acid is not dissociated to monomer. In Huntington's disease, a formic acid-resistant oligomer is present in cerebral cortex, but not in cerebellum. Cortical nuclei contain a polymeric aggregate of expanded polyQ that is insoluble in formic acid, does not enter polyacrylamide gels, but is retained on filters. This finding shows that the process of polymerization is more advanced in the cerebral cortex than in cultured cells. The resistance of oligomer and polymer to formic acid suggests the participation of covalent bonds in their stabilization.

Animals↗

[Anterior cruciate ligament reconstruction: patellar tendon autograft versus four-strand hamstring tendon autografts. A comparative study at one year follow-up].

PURPOSE OF THE STUDY: The purpose of our study was to compare outcome at one year after anterior cruciate ligament reconstruction for chronic laxity using the patellar tendon autograft or four-strand hamstring tendon autografts. MATERIAL AND METHOD: This non-randomized study included 129 consecutive patients operated on between October 1996 and September 1998. Ninety patients were available for assessment at one year: 50 in the patellar tendon group and 40 in the hamstring tendon group. The two groups were comparable for all criteria except sex. A single operator assessed all patients using the IKDC 93 chart. Laxity was measured by comparison with the healthy knee using the KT1000 at maximal manual tension. Preoperative laxity was 8.0 +/- 3.0 mm in the patellar tendon group and 7.6 +/- 3.0 in the hamstring tendon group. All ligamentoplasties were performed arthroscopically using a blind femoral tunnel. The patellar tendon was fixed with two metallic interference screws and the four-strand hamstring autografts with two different methods: an RCI(R) interference screw or a cortical system associating a femoral Endobutton(R) and tibial fixation with a bicortical tibial screw. Lateral tendonesis was performed with the fascia lata in 60% of the patients in the patellar tendon group and in 45% of those in the hamstring tendon group. Rehabilitation exercises were initiated early and were the same in the two groups. RESULTS: Overall results were satisfactory in more than 80% of the patients in both groups. The final IKDC score was significantly better in the patellar tendon group and subjective patient satisfaction was better in the hamstrings group. Residual pain was significantly less pronounced in the hamstrings tendon group (p=0.004). Laxity was improved significantly better in the patellar tendon group: average residual laxity=2.7 +/- 2.1 mm versus 4.5 +/- 2.8 mm (p=0.03) in the hamstrings tendon group; hard stop at the Lachman test in 96% of the patellar tendon group and 78% in the hamstrings tendon group (p=0.007). Residual laxity was significantly less pronounced in the women in the patellar tendon group. There was no significant difference in laxity by type of fixation in the hamstrings tendon group. Recovery in terms of level of activity and type of sport was the same in the two groups. DISCUSSION: These two surgical techniques provide good functional outcome at one year with better control of laxity with patellar tendon autografts and better relief of pain with four-strand hamstrings autografts. Longer follow-up would be useful to assess laxity long after hamstring reconstruction. We compared the type of transplant and the fixation method together as a single unity, but progress in four-strand hamstring autograft fixation will certainly allow even more optimal results and improved correction of laxity. In our opinion, the patellar tendon autograft remains the gold standard for high-performance athletes practicing a contact-pivot sport, but both types of ACL reconstruction are most useful. We select patients for four-strand hamstring tendon reconstruction as a function of age, sex, and type of sports activities.

Adolescent↗

[Arthroscopic release for knee joint stiffness after total knee arthroplasty].

PURPOSE OF THE STUDY: Overall, the results of total knee replacement surgery are quite excellent, both with regard to pain and range of motion. Pain relief is obtained in more than 95% of the cases and more than 90% of the patients are able to bend their knee over 90 degrees. Nevertheless, in a small number of cases, stiffness can be an impairment. MATERIAL AND METHODS: Between 1992 and 1998, six arthroscopic releases were performed on six patients who had undergone total knee replacement. The six patients suffered from unacceptable stiffness. The average age of the patients was 68.5 years, and the time elapsed from implantation to arthroscopy averaged 24 months (6 months to 6 years). Average follow-up was 19 months (6 to 96 months). The six stiff knees were treated with arthroscopic debridement of fibrous tissue around the patella and quadriceps tendon (to improve extension) and by arthroscopic division of the medial and lateral retinacula (to address flexion). A gentle manipulation was carried out following lysis of adhesions, using a slight pressure on the tubercle to avoid fractures and disruptions of the extensor mechanisms. Postoperatively, immediate physical therapy was performed including continuous passive motion and active muscular contraction. Early weight bearing was allowed. RESULTS: The average flexion contracture decreased from 9 degrees prior to arthroscopy to 2.5 degrees at last follow-up. Average flexion increased from 70 to 100 degrees. Maximal improvement was obtained at three months. DISCUSSION: Results were found to be quite good, with a final knee score of 93 and a function score of 92 (following International Knee Society scoring). CONCLUSION: Arthroscopic release following total knee replacement complicated by joint stiffness provides a satisfactory increase in range of motion.

Aged↗

[Anterio-lateral extra-articular tenodesis of the knee using a short strip of fascia lata].

This study describes a lateral extra-articular tenodesis using a short strip of ilio-tibial band. The tenodesis consists of a 12 x 75 mm strip of iliotibial band remaining attached to the Gerdy's tubercle. An isometric point in the region of Krackow's point F-9 is determined with a callipers. The strip of iliotibial band is twisted by 180 degrees to enhance its isometry. Then it is either onlay with a screw and spiked washer on the F-9 point, or within a transverse tunnel drilled through the lateral femoral condyle, from the F-9 point, using and interference screw. Thus, the uses of a short ilio-tibial band tenodesis with a 180 degrees twist in combination with a BPTB reconstruction of the ACL, leads to similar results that the combined classic Lemaire tenodesis, with shorter skin incision, shorter graft harvesting, and at least on the biomechanical standpoint a better graft isometry.

Anterior Cruciate Ligament Injuries↗

[Degenerative lumbar spondylolisthesis treated with isolated intersomatic arthrodesis: results of 30 cases with an average 4-year follow up].

PURPOSE OF THE STUDY: Degenerative spondylolisthesis of the osteoarthritic spine can lead to severe invalidating back pain, decompensating a clinical situation previously well controlled with drugs. Hypothesizing that such invalidating spinal pain might be related to the unstable olisthy, we treated our patients with isolated intersomatic arthrodesis without reducing the displacement. We present here our results in a retrospective analysis of 39 patients who underwent surgery between 1981 and 1992. MATERIAL AND METHODS: Mean age of the 39 patients, 11 men and 28 women, was 62 years (mean, range 37-89). Lumbar spine pain had been well controlled for a mean 10 years. The development of important lumbalgia despite adequate drug treatment led to the indication for surgery in all cases. Thirty-four patients experienced radicular claudication which was severe in 16 cases with a walking distance of less than 100 m. Invalidating radiculalgia occurred in a territory compatible with the olisthy: 33 L4-L5, 2 L5-S1, 4 L2-L3. Twelve patients had a neurological deficit in the L5 territory. Myelography, performed in 26 patients, demonstrated complete interruption of the opaque column in 10 facing the superior surface of the oisthy and radicular amputation in 13; compression over several levels was observed in 13 cases. Anterior intersomatic arthrodesis was done with an iliac tricortical corticospongious graft, associated with en bloc cement insertion in 3 cases. A strut plate screwed on the adjacent vertebral bodies was adapted to the vertebral displacement that was not modified. The upright position was authorized on day 20-45 with a corset worn until day 90. No procedure was attempted on adjacent levels. Postoperative myelography or MRI was obtained for 30 patients. RESULTS: Mean follow-up was 4 years (range 1-10 years). Transient postoperative paresis (L5) occurred after L4-L5 arthrodesis in 2 patients and phlebitis in 3 patients (one complicated with pulmonary embolism without sequelae). Fusion of the arthrodesis was achieved in all cases. The degree of displacement and the height of the "intersomatic space" was modified little compared with the preoperative situation. Radicular claudication regressed totally in 29 cases (85%) and partially in 5 (15%). Radiculalgia regressed totally in 29 (74%) and partially but substantially in 7 (18%). Lumbalgia regressed totally in 20 cases (54%) and partially in 15 (40%). Function, as assessed wth the Beaujon scale, improved from 8 to 17/20 points. There was one case of secondary degradation with development of radiculalgia related to the level above the arthrodesis in one case. No cause could be identified to explain the failure to relieve preoperative radiculalgia in 8% of the patients. CONCLUSION: Strut plates screwed onto the vertebral bodies enabled intersomatic fusion in all cases. Stabilization of the olisthy alone, without correction of the displacement nor release of the canal, successfully relieved pain in all cases of severe radiculalgia due to osteoarthritic spondylolisthesis and even provided improvement of lumbar pain in patients with various levels of discopathy. Unstable olisthy would thus be the major cause of invalidating pain, particularly radiculalgia in these patients.

Adult↗

Targeted ablation of the murine involucrin gene.

Involucrin is synthesized in abundance during terminal differentiation of keratinocytes. Involucrin is a substrate for transglutaminase and one of the precursors of the cross-linked envelopes present in the corneocytes of the epidermis and other stratified squamous epithelia. These envelopes make an important contribution to the physical resistance of the epidermis. We have generated mice lacking involucrin from embryonic stem cells whose involucrin gene had been ablated by homologous recombination. These mice developed normally, possessed apparently normal epidermis and hair follicles, and made cornified envelopes that could not be distinguished from those of wild-type mice. No compensatory increase of mRNA for other envelope precursors was observed.

Animals↗

Expansion of mouse involucrin by intra-allelic repeat addition.

Involucrin, loricrin and the small proline-rich proteins (SPRRs) are precursors of the cornified envelope of terminally differentiated keratinocytes. The genes for these proteins are closely linked on mouse chromosome 3. Each of the proteins is encoded by a single exon and is largely composed of a segment of short tandem repeats. No size polymorphism of either loricrin or the SPRRs was observed. In contrast, involucrin was found in at least eight polymorphic forms of different size with molecular weights ranging from 51 to 82kDa. Two classes of involucrin alleles were identified. Size polymorphism of involucrin has resulted from the recent expansion of the segment of repeats in one class of alleles, but not in the other. In expanding alleles, repeats were added at a precise location within the segment of repeats, in a 5'-to-3' direction. A study of a large number of allele-specific markers, located on both sides of the site of repeat addition, revealed no evidence for recombination between any of the alleles examined. Expansion of the segment of repeats of the gene for mouse involucrin must result from an intra-allelic process controlled by a cis-acting element, active in one class of alleles, and inactive in the other.

Alleles↗

The expanded CAG repeat associated with juvenile Huntington disease shows a common origin of most or all neurons and glia in human cerebrum.

We have analyzed the size of the expanded poly(CAG) associated with juvenile Huntington disease in the cerebra and the cerebella of five patients. The expanded poly(CAG) was always longer in the cerebrum than in the cerebellum, but the difference in size varied from patient to patient. Except for one patient who possessed an unusually large expansion, very little heterogeneity of size was detected within the cerebrum or within the cerebellum. The larger size of the expanded poly(CAG) in cerebrum must therefore have resulted from a single expansion event that took place early in cerebral development. In both cerebrum and cerebellum, the size of the expanded allele of gray matter was identical to that of white matter. We conclude that most if not all neurons and glia of cerebrum are descended from a common bipotent precursor, which segregated early in neurogenesis from the lineage leading to cerebellar neurons and glia.

Adolescent↗

Expression of involucrin in normal, hyperproliferative and neoplastic mouse keratinocytes.

Involucrin is a protein precursor of the epidermal cornified envelope. Although expression of the human protein has been documented extensively, studies in the mouse have been hampered by a shortage of good antibodies. We describe the production of recombinant mouse involucrin and preparation of rabbit antisera to the protein that work well by immunohistochemistry and Western blotting. We confirm that in normal mouse epidermis the onset of involucrin expression is in the upper spinous layers and inner root sheath of the hair follicle. Involucrin was also detected in the differentiating epithelial cells of normal tongue, oesophagus and bladder. Involucrin was expressed in a subpopulation of mouse keratinocytes cultured in standard or low calcium medium and the proportion of involucrin-positive cells increased during suspension-induced terminal differentiation. Western blotting of keratinocytes from several inbred mouse strains revealed a remarkable heterogeneity in the electrophoretic mobility of involucrin, reflecting inter-strain variation in the number of tandem repeats in the protein. In the hyperproliferative epidermis of healing wounds involucrin was expressed in most of the suprabasal layers. In epidermal papillomas and carcinomas involucrin expression correlated well with degree of histological differentiation. The sites of expression of the mouse protein were thus the same as those previously reported for human involucrin. With the development of the new antibodies we anticipate that involucrin will become as widely used a marker of keratinocyte differentiation in the mouse as it is in the human.

Animals↗