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T Link

Publications and source records attributed to T Link.

At least 19 recordsLinked to original sources

Influence of pattern of menopausal transition on the amount of trabecular bone loss. Results from a 6-year prospective longitudinal study.

INTRODUCTION: Bone density is lower in postmenopausal than in premenopausal women. Recent findings have suggested that accelerated bone loss already begins before menopause. Despite numerous cross-sectional studies on menopause-related bone density, longitudinal data on perimenopausal bone density changes are scarce. This study sought to characterize the dynamics of changes leading to postmenopausal osteopenia and to possibly find the time point at which accelerated bone loss begins. METHODS: We prospectively followed 34 pre-, peri- and early postmenopausal women without prior external hormone use, measuring their lumbar spine trabecular bone density with quantitative computer tomography at 0, 2 and 6 years. The analysis of the changes over time was done in a tri-parted fashion, since menopausal status changed variably for individual subjects: we grouped the participants according to their currently valid menopausal classification for prospective (baseline classification), interim (2 years) and retrospective (6-year classification) analysis. RESULTS: Six different patterns of menopausal transition were identified in our sample. Bone loss in the groups not reaching postmenopause during 6 years of observation was >50% of the maximum bone loss observed during the study period. Invariably for all analyses, the perimenopausal phase with estrogen levels still adequate was associated with the greatest reduction of trabecular bone mineral density, reaching 6.3% loss annually in the lumbar spine. By comparison, the average rate of loss was slower in the early postmenopause; total bone loss differed by pattern of menopausal transition (one-way ANOVA p<0.05). CONCLUSION: The presented data for the first time show the perimenopausal course of trabecular bone loss (as measured by QCT of the lumbar spine). Acceleration of bone loss during perimenopause reached half-maximal values of the total bone loss measured around menopause, despite adequate serum estradiol levels.

Bone Density↗

Bioprocess development for the production of a recombinant MUC1 fusion protein expressed by CHO-K1 cells in protein-free medium.

The mucin MUC1 is a candidate for use in specific immunotherapy against breast cancer, but this requires the large-scale production of a MUC1 antigen. In this study, a bioprocess for the expression of a recombinant MUC1 fusion protein with a cancer associated glycosylation in CHO-K1 cells has been developed. Cells permanently expressing parts of the extracellular portion of MUC1 fused to IgG Fc were directly transferred from adherent growth in serum-containing medium to suspension culture in the protein-free ProCHO4-CDM culture medium. Using the Cellferm-pro system, optimal culture parameter as pH and pO(2) were determined in parallel spinner flask batch cultures. A pH of 6.8-7.0 and a pO(2) of 40% of air saturation was found to give best cell growth and productivity of secreted recombinant protein. Specific productivity strongly depended the pO(2) and correlated with the online monitored oxygen uptake rate (OUR) of the cells, which indicates a positive influence of the rate of oxidative phosphorylation on productivity. The optimised conditions were applied to continuous perfusion culture which gave very high cell densities and space time yields of the recombinant MUC1 fusion protein, allowing production at gram scale. The product degradation was much lower in supernatants from continuous perfusion culture compared to batch mode. Antibodies reacting with cancer associated MUC1 glycoforms strongly bound to the fusion protein, indicating that the desired glycoforms were obtained and suggesting that the recombinant MUC1 protein could be tested for use in immunotherapy.

Animals↗

Magnetic resonance evaluation of the interrelationship between articular cartilage and trabecular bone of the osteoarthritic knee.

OBJECTIVE: To use high-resolution magnetic resonance imaging (MRI) to determine the relationship between articular cartilage degeneration and trabecular bone changes of the femur, condyles and tibia in human knees with osteoarthritis (OA). METHODS: Subjects were divided into three groups: without OA (OA0), mild OA (OA1) and severe OA (OA2). Sagittal images of the knee (0.234 x 0.234mm2, 2-mm slice thickness) were obtained at 1.5T and used for calculating the volume and thickness of the femoral and tibial cartilage. Axial images (0.195 x 0.195mm2, 1-mm slice thickness) were used for calculating the trabecular bone structure parameters: apparent bone volume fraction, trabecular number, trabecular separation and trabecular thickness. RESULTS: Cartilage volume and thickness were less in patients with OA compared to normal controls (P<0.1). Articular cartilage thinning is associated with bone structure loss in the opposite femoral condyle (P<0.05). In varus OA, there were extensive correlations between medial tibia and medial femoral cartilage degeneration, and loss of bone structure in the lateral tibia and lateral condyle. Additional correlations existed between the compartmental differences (lateral minus medial) of cartilage thickness and bone structure. CONCLUSION: Degradation of articular cartilage within a compartment correlates with a loss of bone structure in the opposite compartment. The correlation between the (L-M) differences corroborates this relationship. Malalignment of the knee due to cartilage degeneration is associated with bone formation in the diseased condyle and bone resorption in the opposite compartment.

Age Factors↗

Pitfalls in imaging Hodgkin's disease with computed tomography and positron emission tomography using fluorine-18-fluorodeoxyglucose.

We report on a patient with Hodgkin's disease who presented with hypodense splenic lesions and corresponding increased glucose metabolism in FDG-PET imaging, four months after completion of initial treatment, suggestive of early relapse. Serological testing for toxoplasma gondii, however, showed evidence of a recently reactivated or newly acquired infection. Three weeks after immediate antibiotic treatment with Daraprime and Sulfadiazin, the splenic lesions had completely resolved. Additionally, serological titers for toxoplasma gondii were normalized and whole body FDG-PET imaging showed no metabolic activity. Although the positive predictive value of PET imaging to indicate lymphoma is reported to be higher than CT, hypermetabolic lesions are not specific for malignant tissue. Whereas benign tumors typically show low glucose metabolism, activated granulocytes and macrophages may display significantly increased glucose consumption. In conclusion, our case report shows that although therapeutic decisions are often based on the results of imaging modalities, the taking of a detailed history and the acquisition of histological confirmation of the suspected lymphoma relapse are also advisable where possible. Cellular immunodeficiency can result in severe infections even in patients with intermediate stage Hodgkin's lymphoma in remission after combined modality treatment. Therefore, despite the high sensitivity of FDG-PET imaging for the detection of recurrent lymphoma, the differential diagnosis of infectious lesions should be kept in mind, in particular in immunocompromised patients.

Adult↗

Pullout strength of pedicle screws versus pedicle and laminar hooks in the thoracic spine.

While the biomechanical properties of pedicle screws have proven to be superior in the lumbar spine, little is known concerning pullout strength of pedicle screws in comparison to hooks in the thoracic spine. In vitro biomechanical pullout testing was performed to evaluate the axial pullout strength of pedicle screws versus pedicle and laminar hooks in the thoracic spine with regard to surgical correction techniques in scoliosis. Nine human cadaveric thoracic spines were harvested and disarticulated. To simulate a typical posterior segmental scoliosis instrumentation, standard pedicle hooks were used between T4 and T8 and supralaminar hooks between T9 and T12 and tested against pedicle screws. The pedicle screws were loaded strictly longitudinal to their axis; the hooks were loaded perpendicular to the intended rod direction. In total, 90 pullout tests were performed. Average pullout strength of the pedicle screws was significantly higher than in the hook group (T4-T8: 531 N versus 321 N, T9-T12: 807 N versus 600 N, p < 0.05). Both screw diameter and the bone mineral density (BMD) had significant influence on the pullout strength in the screw group. For scoliosis correction, pedicle screws might be beneficial, especially for rigid thoracic curves, since they are significantly more resistant to axial pullout than both pedicle and laminar hooks.

Aged↗

Eukaryotically encoded and chloroplast-located rubredoxin is associated with photosystem II.

We analyzed a eukaryotically encoded rubredoxin from the cryptomonad Guillardia theta and identified additional domains at the N- and C-termini in comparison to known prokaryotic paralogous molecules. The cryptophytic N-terminal extension was shown to be a transit peptide for intracellular targeting of the protein to the plastid, whereas a C-terminal domain represents a membrane anchor. Rubredoxin was identified in all tested phototrophic eukaryotes. Presumably facilitated by its C-terminal extension, nucleomorph-encoded rubredoxin (nmRub) is associated with the thylakoid membrane. Association with photosystem II (PSII) was demonstrated by co-localization of nmRub and PSII membrane particles and PSII core complexes and confirmed by comparative electron paramagnetic resonance measurements. The midpoint potential of nmRub was determined as +125 mV, which is the highest redox potential of all known rubredoxins. Therefore, nmRub provides a striking example of the ability of the protein environment to tune the redox potentials of metal sites, allowing for evolutionary adaption in specific electron transport systems, as for example that coupled to the PSII pathway.

Biological Transport↗

Segmental pedicle screw instrumentation in idiopathic thoracolumbar and lumbar scoliosis.

The role of posterior correction and fusion in thoracolumbar and lumbar scoliosis as well as pedicle screw instrumentation in scoliosis surgery are matters of debate. Our hypothesis was that in lumbar and thoracolumbar scoliosis, segmental pedicle screw instrumentation is safe and enables a good frontal and sagittal plane correction with a fusion length comparable to anterior instrumentation. In a prospective clinical trial, 12 consecutive patients with idiopathic thoracolumbar or lumbar scolioses of between 40 degrees and 60 degrees Cobb angle underwent segmental pedicle screw instrumentation. Minimum follow-up was 4 years (range 48-60 months). Fusion length was defined according to the rules for Zielke instrumentation, normally ranging between the end vertebrae of the major curve. Radiometric analysis included coronal and sagittal plane correction. Additionally, the accuracy of pedicle screw placement was measured by use of postoperative computed tomographic scans. Major curve correction averaged 64.6%, with a loss of correction of 3 degrees. The tilt angle was corrected by 67.0%, the compensatory thoracic curve corrected spontaneously according to the flexibility on the preoperative bending films, and led to a satisfactory frontal balance in all cases. Average fusion length was the same as that of the major curve. Pathological thoracolumbar kyphosis was completely corrected in all but one case. One patient required surgical revision with extension of the fusion to the midthoracic spine due to a painful junctional kyphosis. Eighty-five of 104 screws were graded "within the pedicle", 10 screws had penetrated laterally, 5 screws bilaterally and 4 screws medially. No neurological complications were noted. In conclusion, despite the limited number of patients, this study shows that segmental pedicle screw instrumentation is a safe and effective procedure in the surgical correction of both frontal and sagittal plane deformity in thoracolumbar and lumbar scoliosis of less than 60 degrees, with a short fusion length, comparable to anterior fusion techniques, and minimal loss of correction.

Adolescent↗

Sustained mammary gland-directed, ponasterone A-inducible expression in transgenic mice.

The ability to regulate temporal- and spatial-specific expression of target genes in transgenic mice will facilitate analysis of gene function and enable the generation of murine models of human diseases. The genetic analysis of mammary gland tumorigenesis requires the development of mammary gland-specific transgenics, which are tightly regulated throughout the adult mammary epithelium. Analysis of genes implicated in mammary gland tumorigenesis has been hampered by mosaic transgene expression and the findings that homozygous deletion of several candidate genes (cyclin D1, Stat5A, prolactin receptor) abrogates normal mammary gland development. We describe the development of transgenic mouse lines in which sustained transgene expression was inducibly regulated, both specifically and homogeneously, in the adult mammary gland epithelium. Transgenes encoding RXRalpha and a chimeric ecdysone receptor under control of a modified MMTV-LTR, which targets mammary gland expression, were used. These transgenic 'receptor' lines were crossed with transgenic 'enhancer' lines in which the ecdysone/RXR binding site induced ligand-dependent expression of transgenic beta-galactosidase. Pharmacokinetic analysis of a highly bioactive ligand (ponasterone A), identified through screening ecdysteroids from local plants, demonstrated sustained release and transgene expression in vivo. This transgenic model with both tightly regulated and homogeneous transgene expression, which was sustained in vivo using ligands readily extracted from local flora, has broad practical applicability for genetic analysis of mammary gland disease.

Animals↗

Osteoid osteoma.

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Bone Neoplasms↗

Measurement of skeletal status after renal transplantation by quantitative ultrasound.

BACKGROUND: Osteoporosis remains a major problem following kidney transplantation. Radiographic measures of bone mass are of limited predictive value after transplantation and are complicated by preexisting renal osteopathy. Quantitative ultrasound (QUS) is a new and non-invasive method to assess skeletal status, however, no data exist on ultrasonic bone parameter after kidney transplantation. We evaluated the potential use of this novel method in renal allograft recipients and studied the accuracy compared to normal controls. METHOD: Thirty patients (NTP, age 47.5 +/- 13.0 years) were studied 4.8 +/- 3.2 years after transplantation. Twenty-five healthy control persons (CON) were matched for age and sex. The left and right os calcis were studied by QUS and speed of sound (SOS) and broadband ultrasound attenuation (BUA) were measured. Bone stiffness (BS) was calculated from these parameters and corrected for age (CBS). Differences between right and left os calcis were compared to CON to assess the side variability. RESULTS: Mean +/- SD BS was 75 +/- 22% compared to young adults, age-corrected CBS was decreased in NTP with 86 +/- 25% of normal, indicating a two-fold increased risk of fracture. SOS was 1525 +/- 47.7 m/s, BUA 105 +/- 22 dB/MHz. Mean difference between right and left os calcis was significantly higher in NTP than in CON (7.2 +/- 7.1% vs. 2.1 +/- 2.1%, p < 0.01). Limits of agreement of the measurements (MW of differences +/- 2 SD) according to a Bland-Altmann-type statistic were -16.9% and 20.7%. There was no correlation between CBS and age, cumulative steroid dose, parathyroid hormone concentrations or time after transplantation. CONCLUSION: Our data show altered bone structure expressed by low bone stiffness values measured by quantitative ultrasound in kidney transplant patients. However, because of relatively high inter-feet variance of QUS results we suggest measurement of both ossa calcis to minimize measurement error after transplantation.

Biomechanical Phenomena↗

Fractal analysis of proximal femur radiographs: correlation with biomechanical properties and bone mineral density.

Conventional radiography and fractal analysis were used to quantify trabecular texture patterns in human femur specimens and these measures were used in conjunction with bone mineral density (BMD) to predict bone strength. Radiographs were obtained from 51 human femur specimens (25 male, 26 female). The radiographs were analyzed using three different fractal geometry based techniques, namely semi-variance, surface area and Fourier analysis. Maximum compressive strength (MCS) and shear stress (MSS) were determined with a material testing machine: BMD was measured using quantitative computed tomography (QCT). MCS and MSS both correlated significantly with BMD (MCS: R = 0.49-0.54; MSS: R = 0.69-0.72). Fractal dimension also correlated significantly with both biomechanical properties (MCS: R = 0.49-0.56; MSS: R = 0.47-0.54). Using multivariate regression analysis, the fractal dimension in addition to BMD improved correlations versus biomechanical properties. Both BMD and fractal dimension showed statistically significant correlation with bone strength. The fractal dimension provided additional information beyond BMD in correlating with biomechanical properties.

Adult↗

Ultrasound velocity of trabecular cubes reflects mainly bone density and elasticity.

Studies have indicated that quantitative ultrasound (QUS) variables may be influenced by the mechanical properties of bone which in turn are determined by bone's material and structural properties. However, from these studies it is unclear what role density, elasticity, and structure play in determining velocity. Eighteen defatted, 12-mm cubic trabecular bone specimens were cut from cadaveric specimens. Amplitude-dependent speed of sound (SOS) using a single point QUS system was assessed in three orthogonal axes. Magnetic resonance images were obtained, from which measures of apparent trabeuclar structure were derived. The specimens were nondestructively tested in compression along three orthogonal axes defined by the sides of the cubes. The elastic modulus (in the three directions) and the strength (in one direction) were determined. Trabecular BMD was measured by quantitative computed tomography. SOS varied significantly with direction of measurement, with the highest value in the axial direction (axial:1715 m/s, sagittal: 1662 m/second, and coronal: 1676 m/s). SOS of each of the three axes was generally associated with the various mechanical (r = 0.30-0.87), density (r = 0.81-0.93), and bone structural variables (0.3-0.8). However, after adjusting the SOS correlations by density, only the correlation with elasticity remained significant in the coronal direction. BMD alone explained 88-93% of variance in SOS whereas in the multivariate model, BMD plus elasticity and/or anisotropic variables explained 96-98% of the variance in SOS. Variability of SOS is explained mostly by density and to a small extent by elasticity or anisotropy. Since only 2-6% of the variance of the QUS measurement is not explained by density and elasticity, one could conclude that the remaining variance reflects other properties of bone or perhaps simply measurement error. Evidence that these other properties may be structure related is only found in the anisotropy of QUS parameter.

Adult↗

Fractal analysis of radiographs: assessment of trabecular bone structure and prediction of elastic modulus and strength.

The purpose of this study was to determine whether fractal dimension of radiographs provide measures of trabecular bone structure which correlate with bone mineral density (BMD) and bone biomechanics, and whether these relationships depend on the technique used to calculate the fractal dimension. Eighty seven cubic specimen of human trabecular bone were obtained from the vertebrae and femur. The cubes were radiographed along all three orientations--superior-inferior (SI), medial-lateral (ML), and anterior-posterior (AP), digitized, corrected for background variations, and fractal based techniques were applied to quantify trabecular structure. Three different techniques namely, semivariance, surface area, and power spectral methods were used. The specimens were tested in compression along three orientations and the Young's modulus (YM) was determined. Compressive strength was measured along the SI direction. Quantitative computed tomography was used to measure trabecular BMD. High-resolution magnetic-resonance images were used to obtain three-dimensional measures of trabecular architecture such as the apparent bone volume fraction, trabecular thickness, spacing, and number. The measures of trabecular structure computed in the different directions showed significant differences (p<0.05). The correlation between BMD, YM, strength, and the fractal dimension were direction and technique dependent. The trends of variation of the fractal dimension with BMD and biomechanical properties also depended on the technique and the range of resolutions over which the data was analyzed. The fractal dimension showed varying trends with bone mineral density changes, and these trends also depended on the range of frequencies over which the fractal dimension was measured. For example, using the power spectral method the fractal dimension increased with BMD when computed over a lower range of spatial frequencies and decreased for higher ranges. However, for the surface area technique the fractal dimension increased with increasing BMD. Fractal measures showed better correlation with trabecular spacing and number, compared to trabecular thickness. In a multivariate regression model inclusion of some of the fractal measures in addition to BMD improved the prediction of strength and elastic modulus. Thus, fractal based texture analysis of radiographs are technique dependent, but may be used to quantify trabecular structure and have a potentially valuable impact in the study of osteoporosis.

Biomechanical Phenomena↗

Multicentric malignant transformation of multiple exostoses.

We treated a patient with large multiple chondrosarcomas derived from multiple cartilaginous exostoses. One sarcoma originated in the left pubic bone and the other sarcoma in the posterior aspect of the greater trochanter of the left femur. Thirty months after hindquarter amputation, the patient is alive without relapse. This is the first report of a patient with synchronous multiple malignant transformation of multiple cartilaginous exostoses.

Aged↗

Anisotropy of the elastic modulus of trabecular bone specimens from different anatomical locations.

To associate the mechanical anisotropy of trabecular bone with the relationship between bone mineral density (BMD) and mechanical properties, 97 cubic specimens of human trabecular bone were imaged with computed tomography. Bone cubes from the spine, the calcaneus, the distal, and the proximal femur were tested multidirectionally to measure their compressive stiffness and to calculate their ratios of mechanical anisotropy. The ultimate strength was determined in a destructive test in cephalo-caudal (c-c) direction. Compressive stiffness was largest in the c-c direction for the specimens from the spine, as well as the distal and the proximal femur, but not the calcaneus. Anisotropy ratios in c-c direction were larger at the distal femur and the spine than in the proximal femur. The predictive power of BMD for the mechanical properties varied with anatomical location and strongly depended on the loading direction. While at the spine the c-c stiffness was highly correlated to BMD (r2 = 0.73), the perpendicular directions showed only modest correlations (r2 < 0.53). The correlations of mechanical properties with BMD were greatest at locations where the anisotropy was less pronounced (proximal femur) or rather uniform (spine). The data suggest that BMD can be most successfully applied to determine the mechanical properties in the principal loading direction, which from a clinical perspective may be most relevant.

Adult↗

Transarticular invasion of iliopelvic sarcomas into the sacrum. Radiological analysis of 47 cases.

Joint cartilage functions as a barrier against the extension of bone tumors. However, transarticular invasion by iliopelvic sarcomas across the sacroiliac (SI) joints into the sacrum sometimes occurs. We made a radiological analysis (CT and/or MRI) of 47 bone sarcomas which originated in the ilium and extended nearly to the SI joint 8 of 17 chondrosarcomas and 3 of 30 other sarcomas (2 of 23 Ewing's sarcomas and 1 of 7 osteosarcomas) invaded the sacrum through the SI joint.

Adolescent↗

[Comparison between direct radiographic enlargement and mammography technique in detection of osseous changes of the hand skeleton in hyperparathyroidism].

PURPOSE: To compare direct magnification radiography and mammographic film-screen systems in osseous changes of the hand in hyperparathyroidism. MATERIALS AND METHODS: The hands of 60 patients who were suspected to have primary (5), secondary or tertiary (both 55) hyperparathyroidism were evaluated with direct magnification radiography and a mammographic film-screen system (S12.5). Posterior-anterior views of each hand were obtained with both techniques. The magnification radiographs were made with a focal spot size of 40 or 60 microns, digital luminescence radiography (S600/1200), and a x 6 or 8 magnification. The 240 films were evaluated for subperiosteal, intracortical and endosteal resorptive changes by five radiologists using a grading according to five levels of confidence. RESULTS: A significant improvement (p < 0.05) in the diagnosis of periosteal and intracortical bone resorption was shown, but no significant changes in endosteal resorption with direct magnification radiography. As compared to mammographic film-screen systems, magnification radiography improved the diagnostic accuracy (24%). The time needed for the evaluation of periosteal and intracortical bone resorption was shortened with direct magnification radiography (-4%/ -15%), and the time for giving the diagnosis decreased (-10%).

Adult↗