The Genomics of Cannabis and Its Close Relatives.

Cannabis sativa L. is an important yet controversial plant with a long history of recreational, medicinal, industrial, and agricultural use, and together with its sister genus Humulus, it represents a group of plants with a myriad of academic, agricultural, pharmaceutical, industrial, and social interests. We have performed a meta-analysis of pooled published genomics data, andwe present a comprehensive literature review on the evolutionary history of Cannabis and Humulus, including medicinal and industrial applications. We demonstrate that current Cannabis genome assemblies are incomplete, with ∼10% missing, 10-25% unmapped, and 45S and 5S ribosomal DNA clusters as well as centromeres/satellite sequences not represented. These assemblies are also ordered at a low resolution, and their consensus quality clouds the accurate annotation of complete, partial, and pseudogenized gene copies. Considering the importance of genomics in the development of any crop, this analysis underlines the need for a coordinated effort to quantify the genetic and biochemical diversity of this species.

Anterior screw-plate fixation in adolescent idiopathic scoliosis: 15-year outcomes.

BACKGROUND: Few published data are available on long-term outcomes of anterior spinal fusion for adolescent idiopathic scoliosis (AIS). The objective of this single-centre retrospective study was to assess clinical and radiological outcomes of one-stage anterior spinal fusion achieved using precontoured titanium anterior screw-plates. HYPOTHESIS: Our hypothesis was that anterior instrumentation produced both good functional outcomes and good correction in the coronal and sagittal planes. MATERIAL AND METHODS: This procedure was performed in 111 patients between 1975 and 1993. Among them, those who underwent a comprehensive evaluation at least 15 years later were included. The SRS-30 questionnaire and Oswestry Disability Index (ODI) were used to assess functional outcomes. Radiographic outcomes were evaluated on antero-posterior and lateral full-spine radiographs obtained pre-operatively, post-operatively, and at last follow-up. RESULTS: The study included 35 patients, who were re-evaluated after a mean of 21 years (15-31 years). Mean pre-operative Cobb's angle was 44°, mean age at surgery was 14.7 years, mean SRS-30 score was 3.65/5, and mean ODI was 14.9%. At last follow-up, mean Cobb's angle was 14.7° and 25 patients exhibited coronal misalignment with a mean deviation of 12mm. In the sagittal plane, the mean sagittal vertical axis (SVA) measured using the C7 plumb line was -28mm, with 8mm of anterior translation compared to the post-operative value (36mm). The functional outcome assessed using the SRS-30 score correlated significantly with pelvic tilt and anterior SVA translation. CONCLUSION: Anterior spinal fusion produces good long-term functional outcomes in AIS. Correction is both satisfactory and sustained. Anterior SVA translation over time may be associated with better functional outcomes. LEVEL OF EVIDENCE: IV (retrospective study).

[Congenital pseudarthrosis of the clavicle: 25 childhood cases]. / Pseudarthrose congénitale de la clavicule.

PURPOSE OF THE STUDY: Congenital pseudarthrosis of the clavicle is rare, only 200 cases having been reported. Based on 25 personal cases and an overview of the literature, we try to explain the etiology of this condition and the different kinds of treatment. MATERIAL AND METHODS: A retrospective analysis was performed on twenty-five children (16 females, 9 males, mean age at the end of the follow up - 11.5 yrs) from three different centers. We assessed the outcome of surgical and nonsurgical procedures, based on pain, functional ability, cosmetic results, and x-ray examination. RESULTS: A family background was noted in three children. The lesion always involved the right side. Twenty patients presented a bump over the middle third of the clavicle, thirteen a foreshortened shoulder girdle, three complained of discomfort. In two cases, palpation of the clavicular area was painful. No neurovascular compressive syndrome was reported. None of the patients complained of a decrease in the range of motion or in the strength of the upper limb. X-rays showed a middle third defect. In five cases we found abnormal first ribs. Seventeen patients underwent surgery, at a mean age of 6 years and 4 months. The procedure always included excision of the pseudarthrosis at both ends and internal fixation with a wire or a plate. In only eight cases a bone graft was used. Healing was achieved in fourteen patients. Three patients needed a second surgical procedure. In these 3 cases we had not used bone grafting. All patients had a normal range of shoulder motion, except a twelve year old girl who complained of discomfort of the right upper limb. The cosmetic result was good in eleven cases, one surgical wound was noted as hypertrophic, and one developed a keloid. An asymmetry of the trunk was still noted in seven cases. The x-rays showed symmetric clavicles in ten cases. Eight patients were treated conservatively. All of them had a normal range of motion of the shoulder, six had a good cosmetic result and two cases a poor one. DISCUSSION: According to Alldred, the anomaly results from the failed coalescence of the two primary ossification centers of the clavicle. The overview of the literature and our findings (in one case) confirm that the cartilage which covers both ends of the bone is made of growth cartilage. However, the true mechanism of the nonunion is still unknown. The three familial cases of our work suggest a possible genetic transmission of the disease. The diagnosis is based on the following criteria: right side lesion, found in infancy, without previous fracture, increasing size with growth, without major functional consequences, without neurofibromatosis or cleidocranial dysostosis symptom. X-rays or histologic examination will confirm the diagnosis showing the usual findings described above. Complications of the pseudarthrosis of the clavicle are rare and late. Conservative management appears to give good results as seen with our eight patients. However surgical treatment ensures symmetrical shoulder girdles and good function with few complications. Therefore, we recommend performing an excision of the cartilaginous caps, followed by an iliac bone graft and an internal fixation with wire. Surgical management will be preferred in symptomatic patients, in the case of major or increasing deformity, or on parental request.

Recombinational and physical mapping of the locus for primary open-angle glaucoma (GLC1A) on chromosome 1q23-q25.

Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness in industrialized countries. A locus for juvenile-onset POAG, GLC1A, has been mapped to 1q21-q31 in a 9-cM interval. With recombinant haplotypes, we have now reduced the GLC1A interval to a maximum of 3 cM, between the D1S452/NGA1/D1S210 and NGA5 loci. These loci are 2.8 Mb apart on a 4.7-Mb contig that we have completed between the D1S2851 and D1S218 loci and that includes 96 YAC clones and 48 STSs. The new GLC1A interval itself is now covered by 25 YACs, 30 STSs, and 16 restriction enzyme site landmarks. The lack of a NotI site suggests that the region has few CpG islands and a low gene content. This is compatible with its predominant cytogenetic location on the 1q24 G-band. Finally, we have excluded important candidate genes, including genes coding for three ATPases (ATP1B1, ATP2B4, ATP1A2), an ion channel (VDAC4), antithrombine III (AT3), and prostaglandin synthase (PTGS2). Our results provide a basis to identify the GLC1A gene.

[A method of cost evaluation of orthopedic treatment of femoral diaphyseal fractures in school-age children]. / Une méthode d'évaluation du coût du traitement orthopédique des fractures diaphysaires du fémur chez l'enfant d'âge scolaire.

PURPOSE OF THE STUDY: Femoral diaphysis fractures are very frequent in children. The objective of this study was to evaluate the cost of orthopaedic treatment for femoral diaphysis fracture in school's age children. MATERIAL AND METHODS: 50 femoral fractures were reviewed at an average of 5 years follow-up with many economic parameters. DISCUSSION: Different treatments are available for this type of fracture. Actually, there is a controversy between orthopaedic and surgical treatment and no one gives better long term results. Therefore economic reasons can help for the choice of the method when the final result is equivalent. The same study should be realized for other available fracture treatments. CONCLUSION: Future studies should use the same methodology in order to obtain the real cost of each treatment.

[Pyogenic sacroiliitis in children. Apropos of 11 cases]. / Sacro-iliites à pyogène de l'enfant. A propos de 11 cas.

PURPOSE OF THE STUDY: Sacroiliitis in children is a rare disease. Since 1878, only 100 cases have been reported in the international literature. MATERIALS AND METHODS: We reviewed a series of 11 cases (mean age of 7.75 years) with a delay of 45 months. All the patients had limp, and hip pain. RESULTS: The clinical examination found each time F.A.B.E.R.E. and Glaensen signs. The hip mobility was limited most of time. There was a non specific inflammatory syndrome. Roentgenogram signs were delayed, and associated widening of the joint, geodes, condensation, and at an ultimate stage, fusion of the joint. Tc 99m scintigraphy always showed the localisation. DISCUSSION: This examination shortened the diagnosis delay, C-T scan was performed twice. It allowed visualize the local extension and complication such as abscess. It facilitated the indication of the surgical approach, and results can be appreciated through follow up CT scan studies. The germ was rarely determined as it has been reported in the literature. Therefore an articular ponction must be performed each time a sacroiliitis is suspected, under general anesthesia and associated to an arthrography or under CT scan control. Surgical drains were placed five times only. The authors limited their indication to an important collection, an abscess, or an intra-articular sequestra. CONCLUSION: At the maximum follow up (mean 45 months) all patients had a normal clinical exam. Each time there were joint modification on the roentgenogramm but without any functional correlation.

Nosocomial outbreak of Clostridium difficile diarrhea in a pediatric service.

An outbreak of nosocomial diarrhea that occurred in a pediatric orthopedic service between 1 December 1993 and 15 April 1994 is reported. A total of 37 patients (mean age, 9.6 years; range, 2 months-19.3 years) were involved in the outbreak, including six patients with bacteriologically documented Clostridium difficile infection. A multivariate analysis identified lincomycin treatment for at least three days as the only significant risk factor. Stool samples from four asymptomatic patients were also positive for Clostridium difficile and its cytotoxins. Isolates from all patients belonged to serogroup C, were highly resistant to lincomycin, and exhibited the same restriction pattern by pulsed-field gel electrophoresis. The outbreak ended after treatment with lincomycin was discontinued and hygiene control measures were implemented.

Survey of CAG/CTG repeats in human cDNAs representing new genes: candidates for inherited neurological disorders.

Expansion of polymorphic CAG and CTG repeats in transcripts is the cause of six inherited neurodegenerative or neuromuscular diseases and may be involved in several other genetic disorders of the central nervous system. To identify new candidate genes, we have undertaken a large-scale screening project for CAG and CTG repeats in human reference cDNAs. We screened 100 128 brain cDNAs by hybridization. We also scanned GenBank expressed sequence tags for the presence of long CAG/CTG repeats in the extremities of cDNAs from several human tissues. Of the selected clones, 286 were found to represent new genes, and 72 have thus far been shown to contain CAG/CTG repeats. Our data indicate that CAG/CTG repeated 10 or more times are more likely to be polymorphic, and that new 3'-directed cDNAs with such repeats are very rare (1/2862). Nine new cDNAs containing polymorphic (observed heterozygote frequency: 0.05-0.90) CAG/CTG repeats have been currently identified in cDNAs. All of the cDNAs have been assigned to chromosomes, and six of them could be mapped with YACs to 1q32-q41, 3p14, 4q28, 3p21 and 12q13.3, 13q13.1-q13.2, and 19q13.43. Three of these clones are highly polymorphic and represent the most likely candidate genes for inherited neurodegenerative diseases and, perhaps, neuropsychiatric disorders of multifactorial origin.

[Total hip prosthesis for chronic juvenile arthritis. A review of a series of 34 prosthesis]. / Arthroplastie totale de hanche dans l'arthrite chronique juvénile. Revue d'une série de 34 prothèses.

PURPOSE OF THE STUDY: The purpose of this study was to analyse the results of total hip arthroplasty for chronic juvenile arthritis in order to evaluate risks, problems and benefits of this procedure. MATERIAL AND METHODS: Between 1984 and 1992, 34 total hip prostheses were implanted for chronic juvenile arthritis in 20 patients. Most prosthesis were Zweymuller cementless prosthesis. Mean follow up was 5 years. RESULTS: Results were good. In 85 per cent of cases, patients had a normal activity recovery. Pain relief was very good since in 80 per cent cases patients had a total indolence. DISCUSSION: Beyond these good clinical results at this mean follow-up, the main interest of this study is to characterize two different periods in the surgical technique. The first period when cemented prosthesis was employed and the second one when cementless femoral implants with screwed acetabular component were used. Cementless prostheses appear to be a satisfying solution in this disease, preserving bones and showing very good radiological and functional results. CONCLUSION: Furthermore, the very low complication rate despite general discomfort may prompt us to use total hip arthroplasty for the treatment of chronic juvenile arthritis.

A YAC contig map of the human genome.

A yeast artificial chromosome library containing 33,000 clones with an average insert size of one megabase of human genomic DNA was extensively analysed by several different procedures for detecting overlaps and positional information. We developed an analysis strategy that resulted, after confirmatory tests, in a YAC contig map reliably covering about 75% of the human genome in 225 contigs having an average size of about ten megabases.

A second-generation YAC contig map of human chromosome 3.

A map of human chromosome 3 which integrates both physical and genetic data has been developed from the fusion of two large collections of markers and corresponding yeast artificial chromosome (YAC) clones. The map contains 972 megabase-sized YACs identified with 593 primary markers, of which 162 are highly polymorphic sequence-tagged sites (STSs) and form a closely spaced genetic linkage map; the remaining markers are hybridization-based. Chromosome 3 is now represented by 24 large YAC contigs whose order and orientation is largely known. The map generated by fusion of these hybridization- and STS-based datasets covers about 80% (over 160 megabases) of the chromosome and will provide the foundation necessary for rapid development of a detailed genetic understanding for this large autosome.

Ataxia with vitamin E deficiency: refinement of genetic localization and analysis of linkage disequilibrium by using new markers in 14 families.

Ataxia with vitamin E deficiency (AVED) is an autosomal recessive disease characterized clinically by neurological symptoms with often striking resemblance to those of Friedreich ataxia. This disorder has been reported previously as familial isolated vitamin E deficiency. We have mapped recently the AVED locus to a 5-cM confidence interval on chromosome 8q by homozygosity mapping in six Mediterranean families. We have now analyzed six new and two previously described families and demonstrate genetic homogeneity despite important clinical variability and wide geographic origins. Analysis of nine new tightly linked microsatellite markers, including four characterized in this study, revealed a predominant but not unique mutation in northern African populations, where this condition is more frequent. Haplotype analysis but also classical recombinations allowed us to refine the AVED position to a 1-cM interval. A YAC contig over this interval was constructed from marker STSs and YAC fingerprint data, in order to facilitate the search of the AVED gene.

[Essential bone cysts in children. Value of systematic cystography. Apropos of a series of 42 cysts]. / Kystes osseux essentiels de l'enfant: intérêt de la kystographie systématique. A propos d'une série de 42 kystes.

INTRODUCTION: The treatment of children's essential bone cysts, is controversial. Intra focal injection of a corticoid, the Methylprednisolone, described by Scaglietti in 1974, given in most of the case serials, a rate of healing of more than 30 per cent. MATERIAL AND METHODS: The case serial we present include 42 essential bone cysts treated between 1975 and 1992 in the orthopaedic department of Necker Enfants Malades hospital. These children have been reviewed with a mean follow up of 4 years. A healing rate over 35 per cent has been noticed. However, some failures stayed completely an understanding even if nothing at the beginning let suppose a slower evolution. RESULTS: Attempting to explain those phenomenes, the authors realised in 70 per cent cases, an opaque cystography, before the Methylprednisolone injection. This simple radiological technique permitted to reveal abnormal aspect in 75 per cent cases. Most of the time, it shows massive-veinous licks in an abnormal veinous system or one or plurial separations of the cystic area. This type of picture could perfectly explain the defect of the corticoids action by a lick of the solution or by a partial unefficacity of the solution because of the separation in the cyst area. The hypothetic idea has been completed by the calcul of the duration of the evolution. Effectively, the cysts showing an abnormal cystography had a longer healing delay compared to the cyst whose cystography was normal. CONCLUSION: The opaque cystography is for us a necessary element in the treatment of essential bones cysts, once the diagnostic is certain and the indication of intra focal corticoid injection has been retained. The radiographic study of the cyst area permits to precise the treatment; for example multiplying the injections in the areas of the cysts when there is separations and overseing the evolution.

[Value of pelvic osteotomy in the management of the hip in children with cerebral palsy]. / Intérêt de l'ostéotomie pelvienne dans la prise en charge de la hanche de l'enfant IMC.

PURPOSE OF THE STUDY: The authors analyzed the effectiveness of pelvic osteotomy for the treatment of hip dislocation or subluxation in CP children. MATERIAL: Fifteen pelvic osteotomies were performed on 11 children aged 30 months to 12 years (mean age 6 years). Seven children suffered from Little's disease. Follow-up averaged 10 years (from 2 to 16). Six children were reviewed at the end of growth (9 cases). METHODS: A Salter or triple osteotomy with adductor release was performed. Four cases had also a proximal femoral osteotomy. RESULTS: Following surgery, the mean Reimers' percentage decreased from 55 to 0 per cent. Correction was perfect in 11 cases, incomplete in 4 but excentration remained under 20 per cent. At the end of growth, 6 out of 9 hips remained stable without any further surgery, 2 hips developed slight excentration (less than 20 per cent) and one recurrent subluxation was treated by proximal femoral osteotomy. Six hips remained stable but their growth was not ended at last review. DISCUSSION: This surgical procedure is compared to others described in literature. Pelvic osteotomy with tenotomy improves acetabular cover and corrects muscle imbalance. Its risks seem overestimated in the literature. Both pelvic and femoral osteotomies are useful in specific cases. CONCLUSION: Triple or Salter osteotomy with adducter release seems to be a useful procedure to restore good hip morphology at the end of growth. No posterior dislocations following this osteotomy were seen in spite of the important correction. Proximal femoral osteotomy is not always necessary.

[Foot deformities in longitudinal ectromelia of the lower limbs]. / Les anomalies du pied dans les ectromélies longitudinales des membres inférieurs.

We have studied 204 feet in 181 children with congenital limb shortening. There were 17 short femurs in 11 children in whom it was impossible to lengthen the leg. Thirteen feet were abnormal. It was necessary to adapt the foot to fit the chosen prosthesis. In 34 children it was possible to correct the length of the short femur. In 21 the feet were normal. 13 had abnormal feet associated with fibular aplasia and deformities included equinovalgus, hind foot synostosis, and deficient rays. In 72 children with congenital hypoplasia or aplasia of the fibula, 76 feet were affected. The function of the foot depends on attaining a stable position beneath the tibia. In 34 children (35 feet), the feet were in a stable position. There were 22 ball and socket ankle joints. Before carrying out leg lengthening, operation was necessary on 9 feet, and a further 13 required operation after lengthening had been carried out. In 34 children (41 feet) there was fibular aplasia. The feet lay in equinovalgus and were often narrow. Only 5 did not have a degree of synostosis. Twenty-three feet in twenty two children were operated on with early soft tissue release, tendon transfer and tibiotalar arthrodesis. This is our treatment of choice. Twenty-seven children had tibial dysplasia which affected 37 feet. The feet lay in equinovarus and in 5 there was partial diplopodia. In the absence of a tibia (19 feet) disarticulation of the knee was carried out. In 12 there was proximal shortening of the tibia which in 9 cases was treated by tibiofibular union. It was possible to retain only 2 feet in a proper position in a lengthened leg. In 30 children (33 feet) both fibular and tibial hypoplasia was present. The feet functioned well. There were 22 ball and socket ankles, 28 narrow feet and numerous synostoses. In limbs with atypical dysplasia 7 abnormal feet were noted. If it is possible to preserve or lengthen the limb it is vital that the foot is retained in a stable position beneath the tibia in order that satisfactory function be obtained. If limb lengthening is impossible, the foot must be adapted to match the prosthesis.

Desepiphysiodesis--elimination of partial premature epiphyseal closure. Experience of 17 cases.

Between 1975 and 1990, 17 growth plates have been operated on by epiphyseal bridge resection. The children were from 4 years and 10 months to 13 years and 10 months old. The etiology of partial closure was traumatic (10 times), caused by therapeutic mistakes (3 times), septic osteomyelitis (1 case), purpura fulminans (1 case), unknown (2 cases). There was always length discrepancy or deformity of bone. The regions that have been subjected to treatment were distal femur, proximal tibia, distal tibia, distal radius. Evaluation of the bone bridge was made by tomoscintigraphies and recently by MR imaging and computed tomoscintigraphy. The bone bridge size was from 2.5% to 60% of the growth plate surface; surgical technique consists of resection of bone bridge connecting epiphysis and metaphysis which is replaced by methyl metacrylate. In 16 cases simultaneous corrective osteotomy was performed. Results are poor, there were only two good results and 8 failures; seven results were medium. The failures can all be explained by mistakes in technique or indication, except one. Indications are post-traumatic narrow bridges in young children. It would be useful to know the vitality of the residual growth plate.

Osteochondritis dissecans of the humeral capitellum in children.

We studied 13 cases of osteochondritis dissecans of capitellum humeri in 12 children, 11 boys and 1 girl, aged between 10 and 15 years. We distinguished this affection from Panner's disease which affects young children and resembles Legg-Perthes-Calvé disease of the hip. Operative treatment was performed in 7 out of 13 elbows for removal of loose bodies or excision of osteochondritis in situ with cartilage damage. In other cases, functional treatment was carried out. At long-term follow-up, ranging from 2 to 13 years, clinical examination demonstrated satisfactory results in 9 cases; in 3 cases limitation of movement was related to fracture of the radial head or to delay in operative treatment for too long. Roentgenographically, changes related to growth disturbance were constantly observed; they involved the radial head, the olecranon, the trochlea and the proximal end of the ulna.

[Non-traumatic myositis ossificans in a child. Review of the literature apropos of a case mimicking malignant tumor]. / Myosite ossifiante non traumatique chez l'enfant. Revue de la littérature: à propos d'un cas simulant une tumeur maligne.

A ten year nine month-old girl was admitted to hospital for a painful inflammatory tumour of the right popliteal area. There was a calcification on X-ray and computerised angiography showed a tumour. MRI showed a heterogenous irregular mass. This looked like a malignant tumour. At surgical biopsy: it was a circonscripta myositis ossificans. This benign tumour of soft tissues, rare in children (25 cases in the literature), had a spontaneous favourable evolution. Differential diagnosis with malignant tumour is well known, but is still difficult. Biopsy is necessary in doubtful cases. We had to remove the mass because of acute pain.