Impact of a deletion of the full-length and short isoform of p75NTR on cholinergic innervation and the population of postmitotic doublecortin positive cells in the dentate gyrus.

Analyses of mice carrying a deletion of the pan-neurotrophin receptor p75NTR have allowed identifying p75NTR as an important structural regulator of the hippocampus. Most of the previous analyses were done using p75NTR (ExIII) knockout mice which still express the short isoform of p75NTR. To scrutinize the role of p75NTR in the hippocampus, we analyzed adult and aged p75NTR (ExIV) knockout mice, in which both, the short and the full-length isoform are deleted. Deletion of these isoforms induced morphological alterations in the adult dentate gyrus (DG), leading to an increase in the thickness of the molecular and granular layer. Based on these observations, we next determined the morphological substrates that might contribute to this phenotype. The cholinergic innervation of the molecular and granular layer of the DG was found to be significantly increased in the knockout mice. Furthermore, adult neurogenesis in the DG was found to be significantly altered with increased numbers of doublecortin (DCX) positive cells and reduced numbers of apoptotic cells in p75NTR (ExIV) knockout mice. However, cell proliferation as measured by phosphohiston H3 (PH3) positive cell numbers was not affected. These morphological alterations (number of DCX-positive cells and increased cholinergic fiber densities) as well as reduced cell death in the DG are likely to contribute to the observed thickening of the granular layer in p75NTR (ExIV) knockout mice. In addition, Sholl-analysis of DCX-positive neurons revealed a higher dendritic complexity and could thus be a possible morphological correlate for the increased thickness of the molecular layer in p75NTR deficient animals. Our data clearly demonstrate that deletion of both, the short and the full-length isoform of p75NTR affects DG morphology, due to alterations of the cholinergic system and an imbalance between neurogenesis and programmed cell death within the subgranular zone.

Radiofrequency-targeted vertebral augmentation versus traditional balloon kyphoplasty: radiographic and morphologic outcomes of an ex vivo biomechanical pilot study.

PURPOSE: Traditional balloon kyphoplasty (BK) is a common treatment for symptomatic vertebral compression fractures. The purpose of this study was to compare a novel vertebral augmentation technique, radiofrequency-targeted vertebral augmentation (RF-TVA), to BK for restoration of vertebral height, cavity creation, and polymethylmethacrylate (PMMA) delivery and interdigitation into the surrounding trabeculae. METHODS: This ex vivo biomechanical pilot study utilized 16 osteoporotic cadaveric vertebral bodies in a standardized fracture model to compare unipedicular RF-TVA (n = 8) to bipedicular BK (n = 8). Four specimens from each group were tested in loaded and unloaded conditions. All specimens were imaged, assessed for height restoration, and sectioned to observe PMMA distribution. A subset of specimens underwent computed tomography scanning to assess cavity creation and trabecular architecture prior to cement delivery. RESULTS: Anterior height restoration was greater with RF-TVA (median: 84%, interquartile range: 62%-95%) compared to BK (median: 69%, interquartile range: 60%-81%), although the difference did not achieve statistical significance (P = 0.16). Anterior height restoration was numerically greater under loaded (median: 70% versus 66%) and unloaded (median: 94% versus 77%) conditions with RF-TVA versus BK. RF-TVA produced more discrete cavities and less native trabecular destruction compared to marked trabecular destruction observed with BK. RF-TVA consistently showed a well-identified focal area of PMMA with an extensive peripheral zone of PMMA interdigitation, providing mechanical interlock into the adjacent intact trabecular matrix. In contrast, BK yielded little evidence of PMMA interdigitation beyond the boundaries created by the balloon tamp due to the crushed trabecular bone peripherally. CONCLUSION: RF-TVA achieves favorable vertebral height restoration with targeted PMMA delivery and less trabecular destruction compared to BK. RF-TVA has potential clinical utility in the aging population with painful osteoporotic vertebral fracture.

Experiência clínica inicial na desmineralização química da valva aórtica: potencial aplicação como procedimento minimamente invasivo / Chemical demineralization of the aortic valve: a potential application and preliminary clinical experience

OBJETIVO: Utilização de nova tecnologia na desmineralização química da valva aórtica, em cirurgia cardíaca com circulação extracorpórea, avaliação de suas alterações hemodinâmicas e reportar eventos relacionados à técnica. MÉTODO: Cinco pacientes, submetidos à revascularização miocárdica e portadores de estenose aórtica leve a moderada, receberam tratamento químico na valva aórtica. A idade dos pacientes variou de 65 a 81 anos, com média de 73 anos; sendo todos do sexo masculino. Um paciente tinha doença uniarterial e quatro, multiarterial (quatro vasos). O gradiente médio variou de 13 a 49 mmHg, com média de 25 mmHg. A área média do orifício aórtico variou de 0,8 a 1,3 cm², com média de 1,1cm². Os antecedentes observados foram: hipertensão arterial, hipercolesterolemia, diabete melito e fumo. RESULTADOS: O período de pinçamento aórtico variou de 94 a 126 minutos, com média de 107 minutos. O tempo de "bypass" variou de 134 a 171 minutos, com média de 152 minutos. O tempo de tratamento variou de 13 a 33 minutos, com média de 28 minutos. Não foi observado nenhum óbito. Complicações pós-operatórias observadas foram: bloqueio atrioventricular total em três pacientes. Não foram observados eventos que comprometessem a integridade da valva aórtica ou provocassem insuficiência aórtica pós-tratamento. Também não se observaram eventos neurológicos, sistêmicos, metabólicos ou hematológicos. O gradiente transvalvar pós-operatório, determinado pelo ecocardiograma, demonstrou melhora no gradiente sistólico e médio. CONCLUSÕES: O tratamento demonstrou ser efetivo e seguro, não causando lesão à valva ou algum evento sistêmico. As alterações do sistema de condução parecem relacionadas com o equipamento e seu sistema de liberação da substância de lavagem. A utilização desta tecnologia poderá ser, no futuro, um importante coadjuvante na substituição da valva aórtica por via transcutânea.

OBJECTIVE: To discuss the use of new technology in the chemical demineralization of the aortic valve in coronary artery bypass surgery, together with its hemodynamic changes and to report events related to the technique. METHOD: Five patients with mild to moderate aortic stenosis submitted to myocardial revascularization underwent chemical treatment of the aortic valve. The patients' ages ranged from 65 to 81 years, with a mean of 73 years. All were men. One patient had the involvement of a single artery and four multiple arteries (four vessels). The gradient ranged from 13 to 49 mmHg, with a mean of 25 mmHg. The size of the aortic orifice ranged from 0.8 to 1.3 cm², with a mean of 1.1 cm². The following antecedents were observed: arterial hypertension, hypercholesterolemia, diabetes mellitus and smoking. RESULTS: The aorta clamping time ranged from 94 to 126 minutes, with a mean of 107 minutes and the bypass time was from 134 to 171 minutes, with a mean of 152 minutes. The time of surgery was from 13 to 33 minutes with a mean of 28 minutes. No deaths were recorded. The only postoperative complication noted was a total AV block in three patients. No events were observed that might impair the integrity of the aortic valve or cause aortic insufficiency following treatment. Likewise, no neurologic, systemic, metabolic or hematologic events were seen. The postoperative transvalvular gradient identified by echocardiography showed an improvement in the systolic gradient and in the mean gradient. CONCLUSIONS: The treatment proved to be effective and safe, causing no lesions of the valve or any systemic event. The changes in the conduction system appear to be related to the equipment and its system of releasing the lavage solution. The use of this technology may, in the future, be an important adjuvant in aorta valve replacement using percutaneous techniques.

Repair of the immature and mature craniofacial skeleton with a carbonated calcium phosphate cement: assessment of biocompatibility, osteoconductivity, and remodeling capacity.

BACKGROUND: The apatite compounds used most commonly in craniofacial reconstruction are highly crystalline and biologically inert ceramics. Because their capacity to be replaced by native bone is limited, they have found little application in repair of the growing craniofacial skeleton. Carbonated calcium phosphate cements more closely resemble the mineral phase of bone, thereby offering enhanced bioresorption and osteoconductivity, but their fate in the immature and mature craniofacial skeleton has not been investigated. METHODS: The authors hypothesized that the capacity for cell-mediated remodeling of carbonated calcium phosphate cements is based on (1) their crystallographic and compositional similarity to the mineral phase of bone and (2) the osteogenic capacity of the host. Four noncritical-sized calvarial defects were created in six 3-week-old and six 16-week-old Yorkshire pigs. The defects were repaired with autologous bone, sintered carbonated calcium phosphate cement disks with a higher crystal order, or carbonated calcium phosphate cement (Norian CRS; Synthes Maxillofacial, West Chester, Pa.). The fourth defect was left empty as a control. Specimens were harvested at 30 and 90 days postoperatively. RESULTS: Empty defects healed with dense fibroconnective tissue in all groups. Autologous bone grafts underwent complete remodeling and replacement with woven bone at both time points. Sintered carbonated calcium phosphate disks demonstrated no bony ingrowth or remodeling. In immature animals, carbonated calcium phosphate cement implants were progressively replaced with woven bone through osteoclast-mediated resorption and osteoblast-mediated bone formation. Only minimal remodeling of the carbonated calcium phosphate cement implants was observed in skeletally mature animals. CONCLUSIONS: The results of these experiments suggest that the extent of remodeling of carbonated calcium phosphate cement is dependent on both the composition of the implant itself and the osteogenic capacity of the host and that carbonated calcium phosphate cement may be used successfully for inlay applications in the immature craniofacial skeleton.

Factors influencing changes in articular cartilage following hemiarthroplasty in sheep.

This study examined the relationship between acetabular cartilage properties after hemiarthroplasty surgery and surgical variables including femoral head size and position. Nineteen sheep received unilateral hip arthroplasties and were euthanized one year post-operatively to harvest the femora and acetabula. Cartilage histology, biochemistry and material properties were determined from samples located in the superior load-bearing region. Femoral head size mismatch, leg length difference, anterior-posterior and medial lateral offset and anteversion were measured. In the acetabulum. substantial cartilage degradation occurred with widespread librillation and significant changes in the biochemical and material properties compared to the intact contralateral joint. Regression analyses on the surgical variables explained 75-80% of the changes in tissue biochemistry but did not explain the material changes. Head size mismatch and leg length difference were the most significant contributors of the five variables examined and therefore may be critical to successful outcome in hemiarthroplasty.

Mechanical evaluation of a carbonated apatite cement in the fixation of unstable intertrochanteric fractures.

We created three-part unstable intertrochanteric fractures in 6 pairs of aged, osteopenic, human, cadaveric femora. Fractures were reduced and fixed with a Dynamic Hip Screw (DHS) (Synthes, Paoli, PA). Two test groups were evaluated: 1. Fixation with DHS, and 2. Fixation with a DHS and calcium phosphate bone cement (Norian SRS (Skeletal Repair System)) augmentation of the fracture line and posteromedial calcar region of the proximal femur. Each femur was loaded to 1,650 N (2.5 body weight) for 10,000 cycles to simulate postoperative load transmission across the fracture construct during normal gait. The load was further increased successively by one body weight for another 10,000 cycles until failure. We evaluated fixation by measuring the amount of sliding of the lag screw of the DHS (shortening) and stiffness of the overall fracture construct (stability). SRS cement-augmented specimens had less shortening (1 mm versus 17 mm) and twice the initial construct stiffness compared to control specimens.