Posterior scoliosis correction with thoracoplasty: effect on pulmonary function with a mean follow-up of 4.8 years.

PURPOSE: To perform a study to investigate the influence of posterior scoliosis surgery and thoracoplasty on pulmonary function. METHODS: This was a retrospective observational study of 37 patients with AIS who underwent posterior instrumented surgical correction with thoracoplasty. There was a minimum of 2 years follow-up. Clinical outcomes were measured using the SRS-22 questionnaires. Radiological outcomes were evaluated using standing posteroanterior and lateral radiographs. All patients had pulmonary function tests to evaluate pulmonary volume and flow (forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC)) both before surgery and at the final follow-up. RESULTS: There were three males and 34 females. The mean age of patients was 14.6 years (range 11-21 years). The mean length of follow was 58 months (range 24-124 months). The average main thoracic Cobb angle in the coronal plane was corrected from 50.0° ± 12.4° preoperatively to 16.6° ± 6.3° postoperatively. The average thoracolumbar Cobb angle in the coronal plane was corrected from 28.2° ± 10.6° preoperatively to 10.1° ± 7.2°. The average thoracic kyphosis angle was corrected from 17.4° ± 11.0° preoperatively to 21.8° ± 10.5°. In terms of the Quality of life Outcomes (QoL), there was a significant increase (p < 0.001) in the mean SRS 22 scores from 3.8 preoperatively to 4.3 postoperatively. A statistically significant increase in the absolute forced expiratory volume in one second (FEV1) from pre-operative values with a p value < 0.001 was seen. There was a statistically significant increase in percentage predicted forced expiratory volume in one second from preoperative values with a p value of 0.008. There was also a statistically significant increase in the absolute forced vital capacity (FVC) from preoperative values with a p value < 0.001. The average percentage predicted forced vital capacity did increase on final follow-up from before surgery, but the increase was not statistically significant. CONCLUSIONS: We have demonstrated that pulmonary function post-thoracoplasty not only reaches pre-operative levels, but significantly surpasses it with regards to the majority of the pulmonary parameters measured in this study. We also demonstrated satisfactory radiological correction and clinical outcomes.

Systematic Review of School Scoliosis Screening.

OBJECTIVES: The aim of this study was to review the literature on school screening and its reported effectiveness. SUMMARY OF BACKGROUND DATA: There is no worldwide consensus concerning the mandating of school screening for scoliosis. This remains a controversial issue. METHODS: The following databases were employed: Medline, Premedline, CINAHL, CENTRAL, AMED, Embase, SCOPUS, Ovid nursing, and Web of Science. These data were generated from the Forward Bend Test, the angle of trunk rotation and Moire topography. The first and second authors each independently screened titles and abstracts for potential studies. Fulltext papers of potential studies were also independently read by the first two authors to identify studies to be included based on strict inclusion/exclusion criteria. A heterogeneity test was performed by testing for the significance of the between-study variance. Publication bias was examined by a funnel plot. RESULTS: We found 20 studies that met our inclusion criteria. The pooled estimate of prevalence of scoliosis curves in the population was 1.1% for curves greater than 10°, and 0.2% for curves greater than 20°. The pooled referral rate to radiography during the screening process was 6.6%. The pooled positive predictive values for detecting curves >10° and >20° were 32.3% and 6.5% respectively. Analysis of data demonstrated significant heterogeneity between studies but was not suggestive of the presence of publication bias. CONCLUSIONS: We support the implementation of scoliosis screening as a means of detecting curves at an early treatable stage. The current available evidence in the literature for routine scoliosis screening is low to moderate. Challenges exist to the school scoliosis screening including a high referral rate to radiology.

Occult subaxial cervical disco-ligamentous injuries in computer tomography negative trauma patients.

PURPOSE: Due to lack of cervical clearance consensus in literature and the devastating consequences of missed cervical injuries, Magnetic resonance imaging (MRI) of the neurologically intact symptomatic patient with negative CT scan is frequently done to rule out disco-ligamentous injuries. This study retrospectively evaluates occult disco-ligamentous injuries detected by MRI in patients with no abnormalities detected by modern multi-detector CT scanning and postulates a new theory of ligamentous stability of cervical spine. METHODS: Cervical spine injury patients treated at a spinal trauma referral centre from 2010 to 2013 were retrospectively identified. Available clinical records and radiographic imaging were reviewed to find neurologically intact symptomatic patients with no identifiable acute cervical spine injury on CT scan but MRI evidence of isolated subaxial disco-ligamentous injuries. Patient demographics, injury profile, and treatment details were extracted. Subaxial Cervical Spine Injury Classification (SLIC) and Denis three-column spinal stability theory were adopted to assess stability of injuries. RESULT: 316/566 cervical spinal admissions had CT and MRI scans. 11 (3.5%) CT negative patients were found to have occult discoligamentous injuries on MRI. The average age (51.1 years) was not significantly different to all cervical trauma admissions (p = 0.09). Eight had flexion type and three had extension type injuries. The most common mechanisms were sports and fall on flat surface. The average SLIC score was 3.1. Four patients were classified as having unstable or potentially unstable injuries (two patients each) and three of these patients were surgically managed. Subtle CT changes to indicate discoligamentous injury could be retrospectively identified in all four of these patients. CONCLUSION: CT scans alone may be inadequate for clearing occult disco-ligamentous injuries of the subaxial cervical spine in trauma. Denis three-column stability theory may be beneficial in determining stability and guiding treatment along with the SLIC system for occult discoligamentous injuries of the subaxial cervical spine.

Hemichordate genomes and deuterostome origins.

Acorn worms, also known as enteropneust (literally, 'gut-breathing') hemichordates, are marine invertebrates that share features with echinoderms and chordates. Together, these three phyla comprise the deuterostomes. Here we report the draft genome sequences of two acorn worms, Saccoglossus kowalevskii and Ptychodera flava. By comparing them with diverse bilaterian genomes, we identify shared traits that were probably inherited from the last common deuterostome ancestor, and then explore evolutionary trajectories leading from this ancestor to hemichordates, echinoderms and chordates. The hemichordate genomes exhibit extensive conserved synteny with amphioxus and other bilaterians, and deeply conserved non-coding sequences that are candidates for conserved gene-regulatory elements. Notably, hemichordates possess a deuterostome-specific genomic cluster of four ordered transcription factor genes, the expression of which is associated with the development of pharyngeal 'gill' slits, the foremost morphological innovation of early deuterostomes, and is probably central to their filter-feeding lifestyle. Comparative analysis reveals numerous deuterostome-specific gene novelties, including genes found in deuterostomes and marine microbes, but not other animals. The putative functions of these genes can be linked to physiological, metabolic and developmental specializations of the filter-feeding ancestor.

Results of the 2014 SRS Survey on PJK/PJF: A Report on Variation of Select SRS Member Practice Patterns, Treatment Indications, and Opinions on Classification Development.

STUDY DESIGN: An electronic survey administered to Scoliosis Research Society membership. OBJECTIVE: To characterize surgeon views regarding proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) management providing the framework in which a PJK/PJF classification system and treatment guidelines could be established. SUMMARY OF BACKGROUND DATA: PJK/PJF are common complications of adult spinal deformity surgery. To date, there is no consensus on PJK/PJF definitions, classification, and indications for revision surgery. There is a paucity of data on deformity surgeon practice pattern variations and consensus opinion on treatment and prevention. METHODS: An electronic 19-question survey regarding PJK/PJF was administered to members of the Scoliosis Research Society who treat adult spinal deformity. Determinants included the surgeons' type of practice, number of years in practice, agreement with given PJK/PJF definitions, importance of key factors influencing prevention and revision, prevention methods currently used, and the importance of developing a classification system. RESULTS: A total of 226 surgeons responded (38.8% response rate). Both 44.4% of surgeons selected "extremely important" and 40.8% selected "very important" that PJK in adult spinal deformity surgery is a very important issue and that a Scoliosis Research Society PJK/PJF classification system and guidelines for detection and prevention of PJK/PJF is a "must have" (18.1%) and "very likely helpful" (31.9%). Both 86.2% and 90.7% of surgeons agreed with the provided definitions of PJK and PJF, respectively. Top 5 revision indications included neurological deficit, severe focal pain, translation or subluxation fracture, a change in kyphosis angle of greater than 30°, chance fracture, spondylolisthesis greater than 6 mm, and instrumentation prominence. The majority of respondents use a PJK/PJF prevention strategy 60% of the time or more, the most common were terminal rod contour, preoperative bone mineral density testing, and frequent radiographical studies during first 3 months postoperative, preoperative bone mineral density medication for low bone mineral density. CONCLUSION: The results of this study provide insight from the practicing surgeons' perspective of the management of PJK and PJF that may aid in the validation of current definitions and consensus-based treatment decisions and prevention guidelines. LEVEL OF EVIDENCE: 5.

Subaxial injury classification scoring system treatment recommendations: external agreement study based on retrospective review of 185 patients.

STUDY DESIGN: Retrospective case series. OBJECTIVE: To test validity of subaxial injury classification (SLIC) treatment recommendations. SUMMARY OF BACKGROUND DATA: Although SLIC has been tested for reliability, external studies that test the validity of its treatment recommendations are lacking. METHODS: The SLIC score was determined by reviewing imaging studies and clinical records in a consecutive series of 185 patients with subaxial cervical spine trauma presenting to a level 1 spinal injury referral center. Details including attending surgeon responsible for treatment decision, treatment received, and surgical approach were collected. RESULTS: Treatment received matched SLIC guidelines in 93.6% nonsurgically managed patients and 96.3% surgically managed patients. The mean SLIC score of the surgically treated group of patients was significantly higher than that of the nonsurgical group (7.14 vs. 2.22; P<0.001). Sixty-six patients had a SLIC score of 3 or less, and 94% of them were nonsurgically managed (P<0.001). One hundred two patients had a SLIC score of 5 or more, and 95% of them were surgically managed (P<0.001). Seventeen patients had a SLIC score of 4, and 65% were nonsurgically managed (P=0.032). Injury morphology scores were not predictive of surgical approach. Increasing SLIC scores correlated with increasing complexity of treatment (r=0.77; P<0.001). The distribution of patients with regard to severity of injuries and treatment delivered by the 7 spinal surgeons was comparable. The past practice of these 7 fellowship-trained spine surgeons was individually in agreement with SLIC treatment recommendations. CONCLUSION: Our past practice reflects SLIC treatment recommendations for nonsurgical treatment of patients with SLIC scores of 3 or less and surgical treatment of patients with SLIC scores of 5 or more. The use of SLIC as an ordinal severity scale is validated as increasing SLIC scores correlated with increasing complexity of treatment. The injury morphology score did not predict a surgical approach. Significantly higher numbers of patients with a SLIC score of 4 were treated nonsurgically. LEVEL OF EVIDENCE: 3.

Laminar screw fixation of the axis in the pediatric population: a series of eight patients.

BACKGROUND CONTEXT: Instability of the atlantoaxial spine is a recognized problem in children. Safe passage of pedicle screws at C2 poses challenges because of the proximity to the vertebral artery, size of the pedicles, and variations in the location of the foramen transversarium. PURPOSE: The C2 translaminar technique is a useful option and its stability is comparable to that offered by C2 pedicle screws. In this follow-up from our previously published study, we wanted to verify the safety and suitability of the C2 laminar screw in the treatment of cervical instability in the pediatric population. STUDY DESIGN/SETTING: We present a case series of eight pediatric patients who underwent laminar screw fixation of the axis as part of their operative procedure. PATIENT SAMPLE: There were five girls and three boys, with a mean age of 7 years (range 2-17 years) who underwent this procedure. Surgical indications included atlantoaxial instability, atlanto-occipital disassociation, multilevel cervical instability, and high cervical stenosis. Seven patients had underlying dysplastic syndromes. OUTCOME MEASURES: We studied the technical feasibility of passing laminar screws at C2 in eight consecutive patients, paying attention to screw length and diameter, vascular or neurologic complications, and stability of fixation. METHODS: This retrospective study was funded by our institution and there was no potential conflict of interest. All patients were placed prone. The posterior aspect of the cervical spine and craniocervical junction were exposed subperiosteally. We report our modification of the Wright technique, which allowed us to safely pass 3.5-mm screws into both laminae of the second cervical vertebra. RESULTS: A total of 15 laminar screws were passed at C2. The follow-up period ranged from 1 to 24 months (mean 8 months). There were no vascular or neurologic complications, no infection, and no instances of hardware failure either by lamina fracture or screw pullout. All patients maintained stable constructs on imaging studies at the last follow-up evaluation. CONCLUSION: Children as young as 2 years can undergo safe and rigid fixation of the axis. The technique is especially valuable in patients with dysplastic bone and distorted anatomy where more traditional methods of C2 fixation cannot be safely used. To our knowledge, this is the largest reported series of C2 laminar screw fixation in a pediatric population.

Proximal junctional kyphosis and failure after spinal deformity surgery: a systematic review of the literature as a background to classification development.

STUDY DESIGN: Systematic review of literature. OBJECTIVE: To perform a comprehensive English language systematic literature review of proximal junctional kyphosis (PJK) and proximal junctional failure (PJF), concentrating on incidence, risk factors, health related quality of life impact, prevention strategy, and classification systems. SUMMARY OF BACKGROUND DATA: PJK and PJF are well described clinical pathologies and are a frequent cause of revision surgery. The development of a PJK classification that correlates with clinical outcomes and guides treatment decisions and possible prevention strategies would be of significant benefit to patients and surgeons. METHODS: The phrases "proximal junctional," "proximal junctional kyphosis," and "proximal junctional failure" were used as search terms in PubMed for all years up to 2014 to identify all articles that included at least one of these terms. RESULTS: Fifty-three articles were identified overall. Eighteen articles assessed for risk factors. Eight studies specifically reviewed prevention strategies. There were no randomized prospective studies. There were 3 published studies that have attempted to classify PJK. The reported incidence of PJK ranged widely, from 5% to 46% in patients undergoing spinal instrumentation and fusion for adult spinal deformity. It is reported that 66% of PJK occurs within 3 months and 80% within 18 months after surgery. The reported revision rates due to PJK range from 13% to 55%. Modifiable and nonmodifiable risk factors for PJK have been characterized. CONCLUSION: PJK and PJF affect many patients after long segment instrumentation after the correction of adult spinal deformity. The epidemiology and risk factors for the disease are well defined. A PJK and PJF scoring system may help describe the severity of disease and guide the need for revision surgery. The development and prospective validation of a PJK classification system is important considering the prevalence of the problem and its clinical and economic impact. LEVEL OF EVIDENCE: N/A.

Gibbon genome and the fast karyotype evolution of small apes.

Gibbons are small arboreal apes that display an accelerated rate of evolutionary chromosomal rearrangement and occupy a key node in the primate phylogeny between Old World monkeys and great apes. Here we present the assembly and analysis of a northern white-cheeked gibbon (Nomascus leucogenys) genome. We describe the propensity for a gibbon-specific retrotransposon (LAVA) to insert into chromosome segregation genes and alter transcription by providing a premature termination site, suggesting a possible molecular mechanism for the genome plasticity of the gibbon lineage. We further show that the gibbon genera (Nomascus, Hylobates, Hoolock and Symphalangus) experienced a near-instantaneous radiation ∼5 million years ago, coincident with major geographical changes in southeast Asia that caused cycles of habitat compression and expansion. Finally, we identify signatures of positive selection in genes important for forelimb development (TBX5) and connective tissues (COL1A1) that may have been involved in the adaptation of gibbons to their arboreal habitat.

Operative treatment of chance injuries in the paediatric population.

PURPOSE: Chance fractures are an uncommon spine injury in the paediatric population. As such there is a relative paucity of evidence in the literature to guide management decisions. We present our single centre experience in the operative management of these injuries. METHODS: All patients presenting to a tertiary paediatric trauma centre between 2000 and 2008 were included. Retrospective analysis of clinical (SRS-22 and Oswestry) and radiological outcomes was undertaken. RESULTS: Twelve patients underwent operative stabilization of a Chance type injury. Radiological and clinical outcome measures demonstrated excellent outcomes in the majority of patients with no significant complications. CONCLUSIONS: Operative management of paediatric chance injuries with instrumentation results in excellent clinical and radiological outcomes.

Strict evolutionary conservation followed rapid gene loss on human and rhesus Y chromosomes.

The human X and Y chromosomes evolved from an ordinary pair of autosomes during the past 200-300 million years. The human MSY (male-specific region of Y chromosome) retains only three percent of the ancestral autosomes' genes owing to genetic decay. This evolutionary decay was driven by a series of five 'stratification' events. Each event suppressed X-Y crossing over within a chromosome segment or 'stratum', incorporated that segment into the MSY and subjected its genes to the erosive forces that attend the absence of crossing over. The last of these events occurred 30 million years ago, 5 million years before the human and Old World monkey lineages diverged. Although speculation abounds regarding ongoing decay and looming extinction of the human Y chromosome, remarkably little is known about how many MSY genes were lost in the human lineage in the 25 million years that have followed its separation from the Old World monkey lineage. To investigate this question, we sequenced the MSY of the rhesus macaque, an Old World monkey, and compared it to the human MSY. We discovered that during the last 25 million years MSY gene loss in the human lineage was limited to the youngest stratum (stratum 5), which comprises three percent of the human MSY. In the older strata, which collectively comprise the bulk of the human MSY, gene loss evidently ceased more than 25 million years ago. Likewise, the rhesus MSY has not lost any older genes (from strata 1-4) during the past 25 million years, despite its major structural differences to the human MSY. The rhesus MSY is simpler, with few amplified gene families or palindromes that might enable intrachromosomal recombination and repair. We present an empirical reconstruction of human MSY evolution in which each stratum transitioned from rapid, exponential loss of ancestral genes to strict conservation through purifying selection.

Deep resequencing reveals excess rare recent variants consistent with explosive population growth.

Accurately determining the distribution of rare variants is an important goal of human genetics, but resequencing of a sample large enough for this purpose has been unfeasible until now. Here, we applied Sanger sequencing of genomic PCR amplicons to resequence the diabetes-associated genes KCNJ11 and HHEX in 13,715 people (10,422 European Americans and 3,293 African Americans) and validated amplicons potentially harbouring rare variants using 454 pyrosequencing. We observed far more variation (expected variant-site count ∼578) than would have been predicted on the basis of earlier surveys, which could only capture the distribution of common variants. By comparison with earlier estimates based on common variants, our model shows a clear genetic signal of accelerating population growth, suggesting that humanity harbours a myriad of rare, deleterious variants, and that disease risk and the burden of disease in contemporary populations may be heavily influenced by the distribution of rare variants.

Functional and evolutionary insights from the genomes of three parasitoid Nasonia species.

We report here genome sequences and comparative analyses of three closely related parasitoid wasps: Nasonia vitripennis, N. giraulti, and N. longicornis. Parasitoids are important regulators of arthropod populations, including major agricultural pests and disease vectors, and Nasonia is an emerging genetic model, particularly for evolutionary and developmental genetics. Key findings include the identification of a functional DNA methylation tool kit; hymenopteran-specific genes including diverse venoms; lateral gene transfers among Pox viruses, Wolbachia, and Nasonia; and the rapid evolution of genes involved in nuclear-mitochondrial interactions that are implicated in speciation. Newly developed genome resources advance Nasonia for genetic research, accelerate mapping and cloning of quantitative trait loci, and will ultimately provide tools and knowledge for further increasing the utility of parasitoids as pest insect-control agents.

Atlantoaxial and craniocervical arthrodesis in children: a tomographic study comparing suitability of C2 pedicles and C2 laminae for screw fixation.

STUDY DESIGN: Analysis of C1-C2 tomographic anatomy in a cohort of healthy children. OBJECTIVE: Compare suitability of C2 laminae and C2 pedicles for screw placement. SUMMARY OF BACKGROUND DATA: Surgeons have applied several techniques for craniocervical and atlantoaxial spondylodesis to address congenital or developmental abnormalities in children. Constructs with pedicle or transarticular screws are effective to stabilize the craniocervical junction; however, these fixation points are not suitable in all patients. Translaminar screw placement in C2 has been safely performed in children; yet, suitability of C2 laminae and C2 pedicles has not been systematically compared. METHODS: Applying chi2 test, we compared suitability for screw placement in 46 C2 pedicles and 46 C2 laminae on digital images of axial reconstructions of cervical CT scans of 23 children who had been admitted to the same hospital due to head or neck injury. On the same scans, we estimated suitability for screw placement in 46 lateral masses of C1. RESULTS: Twenty-four percent of C2 pedicles and 65% of C2 laminae were deemed suitable for 3.5-mm screw placement, and the difference was statistically significant (P < or = 0.0001, chi2 15.88). Forty-one percent of C2 pedicles and 80% of C2 laminae were deemed suitable for 3.0-mm screw placement, and the difference was statistically significant (P < or = 0.0001, chi2 14.78). Ninety-five percent of C1 lateral masses were deemed suitable for 3.5-mm screw placement. CONCLUSION: C2 laminae represent a viable fixation point for C1-C2 and craniocervical arthrodesis in children. This information can be useful for preoperative planning.

Transcranial motor-evoked potentials combined with response recording through compound muscle action potential as the sole modality of spinal cord monitoring in spinal deformity surgery.

STUDY DESIGN: This study is a prospective review of all spinal cord monitoring procedures in our unit from 1999 to 2004 in patients undergoing spinal deformity correction surgery. OBJECTIVE: To report the sensitivity and specificity of transcranial motor-evoked potentials (MEP) and compound muscle action potential (CMAP) monitoring as the sole modality in spinal deformity correction surgery. SUMMARY OF BACKGROUND DATA: Combined spinal cord monitoring with somatosensory-evoked potentials and MEP has been widely used. The use of CMAP as the only modality has not been widely used and its efficacy has not been fully elucidated. METHODS: The intraoperative monitoring outcomes were compared with patient's postoperative clinical outcomes. The sensitivity and specificity were calculated and determined for our monitoring protocol. RESULTS: Transcranial MEPs were measured in 144 patients in 172 procedures. In 2 patients (3 procedures), we were unable to record any CMAPs. There were 15 intraoperative monitoring changes. There were no new postoperative neurological deficits. CONCLUSION: The monitoring criteria are sufficiently strict to achieve a sensitivity of 1.0 and a specificity of 0.97. Monitoring of CMAPs alone has been adequate to avoid clinical neurological deficits.

The genome of the model beetle and pest Tribolium castaneum.

Tribolium castaneum is a member of the most species-rich eukaryotic order, a powerful model organism for the study of generalized insect development, and an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved the ability to interact with a diverse chemical environment, as shown by large expansions in odorant and gustatory receptors, as well as P450 and other detoxification enzymes. Development in Tribolium is more representative of other insects than is Drosophila, a fact reflected in gene content and function. For example, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, some being expressed in the growth zone crucial for axial elongation in short-germ development. Systemic RNA interference in T. castaneum functions differently from that in Caenorhabditis elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.

Evolutionary and biomedical insights from the rhesus macaque genome.

The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species.

Effect of zoledronic acid in an L6-L7 rabbit spine fusion model.

Previous studies have shown that zoledronic acid administration can increase mineral content and strength in distraction osteogenesis. Of the few studies that have examined the use of bisphosphonates in spinal arthrodesis, none have assessed the effect of single dose treatment. The objective of this study was to evaluate the feasibility of enhancing spinal fusion rate using single dose zoledronic acid (ZA) to increase fusion-mass size and mineral density. Forty-eight New Zealand white rabbits underwent an L6-L7 intertransverse process fusion. The L6-L7 model is more challenging than the more commonly used level of L5-L6. Animals were randomly allocated to one of three groups, one received iliac crest bone graft alone, one group received iliac crest bone graft with locally administered zoledronic acid, 20 microg, and one group received iliac crest bone graft with a single dose of systemically administered zoledronic acid, 0.1 mg/kg. ZA doses were administered at the time of surgery. Twenty-four rabbits were culled at 6 weeks and 24 rabbits were culled at 12 weeks. Success of spinal fusion was determined by manual palpation. Specimens were evaluated radiographically, underwent quantitative computerised tomography analysis and were tested biomechanically in flexion and extension. In the six-week group, only five of the 24 spines fused with no noticeable trend with respect to treatment. In the 12-week group there was a trend toward increased fusion in the systemically administered ZA group (63%) versus the other two groups (25%) but was not statistically significant (p = 0.15). Radiographically, the local ZA treatment group showed a delay in remodelling with the presence of unremodelled bone chips. The 12-week systemic ZA group exhibited an 86% increase in BMC, a 31% increase in vBMD and a 41% increase in the volume of the fusion-mass (p < 0.05). The 12-week local ZA group also showed significant increases in BMC (69%), vBMD (31%) and total fusion-mass volume (29%) (p < 0.05). Biomechanical testing showed that the range of motion in flexion decreased to 4.5 (+/-2.5) degrees and 4.8 (+/-4.7) degrees for the local and systemic groups respectively compared to 9.6 (+/-4.9) degrees for the control group (p < 0.05). This study has shown that zoledronic acid increased fusion-mass size and bone mineral content. Systemic ZA led to an increased fusion rate; however the fusion rate remained below 100%. We suggest that bisphosphonate treatment may require an anabolic conjunctive therapy to ensure enhanced successful fusion.

The DNA sequence, annotation and analysis of human chromosome 3.

After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion.

The finished DNA sequence of human chromosome 12.

Human chromosome 12 contains more than 1,400 coding genes and 487 loci that have been directly implicated in human disease. The q arm of chromosome 12 contains one of the largest blocks of linkage disequilibrium found in the human genome. Here we present the finished sequence of human chromosome 12, which has been finished to high quality and spans approximately 132 megabases, representing approximately 4.5% of the human genome. Alignment of the human chromosome 12 sequence across vertebrates reveals the origin of individual segments in chicken, and a unique history of rearrangement through rodent and primate lineages. The rate of base substitutions in recent evolutionary history shows an overall slowing in hominids compared with primates and rodents.