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Biomedical subjects

S A Goldstein

Publications and source records attributed to S A Goldstein.

At least 91 records · Page 5Linked to original sources
PubMed1997

Trabecular bone adaptation to variations in porous-coated implant topology.

Trabecular bone adaptation adjacent to porous-coated platen implants embedded within canine distal femoral metaphyses was evaluated following 24 weeks of daily compressive loading. The in vivo experimental model delivered controlled loads to five different platen implant topologies with variations in platen shape and porous coating distribution. Adaptive changes were evaluated based on three-dimensional stereological analyses of trabecular bone architecture underneath each platen and non-destructive mechanical tests of platen construct stiffness. Fully coated cylindrical platen designs possessed the highest construct stiffness in both tension and compression. Changes in local trabecular bone morphology were also found to be significantly influenced by platen implant topology. Cylindrical platens with fully coated bottom surfaces were associated with greater decreases in trabecular bone volume and connectivity than cylindrical platens with smooth bottom surfaces or fully coated conical platens. Comparisons to site-matched contralateral control bone volumes across all platen designs indicated significant decreases in the average bone volume fraction, trabecular plate number, and connectivity within experimental samples, but no change in trabecular plate thickness. In addition, analyses of microstructural anisotropy revealed a 20 degrees or 20.2 degrees trabecular reorientation towards the axis of loading in experimental tissue. This study demonstrates that trabecular bone adaptation near porous-coated surfaces is influenced by variations in local implant topology and provides insight into specific mechanisms of implant-mediated microstructural adaptation.

Analysis of Variance↗
PubMed1997

Biomechanical evaluation of current patella fracture fixation techniques.

OBJECTIVE: To compare the mechanical effectiveness of three different techniques for stabilization of transverse fractures of the patella. DESIGN: Cadaveric knees were used to model acute fractures of the patella. To test three treatment techniques in pairs of knees, specimen pairs were assigned randomly to a set of predetermined treatment pairs so as to provide equal numbers of paired and unpaired data sets. Results then were analyzed using a two-way analysis of variance. SETTING: The treatment techniques used are widely applicable in the clinical setting for the treatment of transverse fractures of the patella. No specialized equipment or training is required for the general or subspecialized orthopaedic surgeon. PATIENTS/PARTICIPANTS: None. INTERVENTIONS: Fractures were created in eighteen knees (nine pairs) and repaired by one of three techniques: (a) modified tension band (AO technique); (b) two parallel 4.5-millimeter interfragmentary lag screws; or (c) a new technique using four-millimeter cannulated lag screws with a tension band wired through the screws. MAIN OUTCOME MEASURES: In mechanical testing, the amount of interfragmentary separation in simulated knee extension and the maximum load to failure at 45 degrees of flexion were measured. RESULTS: Fractures stabilized with a modified tension band were found to displace significantly more than those fixed with screws alone or screws plus a tension band in simulated knee extensions (p < 0.05). The fractures fixed with the cannulated screws plus the tension band failed at higher loads (mean = 732 newtons) than those stabilized with screws alone (mean = 554 newtons, p = 0.06) or those with a modified tension band (mean = 395 newtons, p < 0.05). CONCLUSIONS: Combining interfragmentary screw fixation with the tension band principle appears to provide improved stability over the modified tension band or screws alone for transverse patella fractures. Cannulated screws allow for simple, reliable addition of a tension band to screw fixation.

Aged↗
PubMed1997

Hip screw augmentation with an in situ-setting calcium phosphate cement: an in vitro biomechanical analysis.

OBJECTIVES/HYPOTHESIS: This study was performed to determine whether a new, in situ-setting calcium phosphate cement would have sufficient mechanical integrity to reinforce compression screw fixation of unstable intertrochanteric fractures. We compared the cut-out resistance of screws augmented with calcium phosphate cement to the cut-out resistance of screws augmented with polymethylmethacrylate (PMMA). We used PMMA as the standard for comparison because it is currently used clinically. Our hypothesis was that initial fixation strength with PMMA and calcium phosphate cement augmentation would not be significantly different from one another. STUDY DESIGN: Cut-out testing of compression hip screws in paired human cadaveric proximal femurs was performed before and after augmentation with PMMA or calcium phosphate cement. Bilateral testing was performed to allow pairwise comparisons of the materials used for augmentation, and repeated testing was done to provide an internal control for the effects of bone quality. The initial fixation of screws augmented with calcium phosphate cement was compared with that of screws augmented with PMMA. METHODS: Ten paired human femurs (mean age, 75 +/- 9.2 years) were implanted with Richards AMBI compression hip screws. Basicervical osteotomies were then performed, yielding isolated proximal fragments for mechanical testing. Preaugmentation cut-out tests were performed under displacement control, with cut-out continuing to five millimeters at two millimeters per second. The screws were then removed, and the screw tracks were filled with 2.0 cubic centimeters of PMMA (one side) or calcium phosphate cement (contralateral side). After augmentation, the screws were reinserted and the cements were allowed to harden for twenty-four hours. Postaugmentation testing followed the protocols for preaugmentation testing, and the initial fixation strength of screws augmented with calcium phosphate cement was compared with the initial fixation strength of screws augmented with PMMA using a two-way repeated measures analysis of variance. RESULTS: The cut-out behavior of screws augmented with calcium phosphate cement was not significantly different from the cut-out behavior of screws augmented with PMMA. With calcium phosphate cement, yield strength increased by 15.8 percent (from 1,354 +/- 632 newtons to 1,568 +/- 320 newtons); with PMMA, the yield strength increased by 26.8 percent (from 1,477 +/- 526 newtons to 1,834 +/- 225 newtons). However, only the increase with PMMA augmentation was significant at p < 0.05). The energy to yield increased significantly (41 percent, p < 0.05) with both types of augmentation (from 2,399 +/- 1,186 newton-millimeters to 3,378 +/- 857 newton-millimeters for calcium phosphate cement, and from 2,635 +/- 1,113 newton-millimeters to 3,741 +/- 426 newton-millimeters for PMMA), whereas the stiffness increased only slightly with PMMA augmentation (6.2 percent, from 481 +/- 180 newtons per millimeter to 511 +/- 92 newtons per millimeter) and fell slightly with calcium phosphate cement augmentation (10 percent, from 457 +/- 201 newtons per millimeter to 411 +/- 663 newtons per millimeter). CONCLUSIONS: The in situ-setting calcium phosphate cement investigated in this study compared favorably with PMMA in a single-cycle cut-out test of augmented compression hip screws in senile trabecular bone. Our results suggest that these materials may have promise as substitutes for PMMA in the salvage of compression hip screw fixation in elderly osteopenic patients with complex intertrochanteric fractures and that further study of their use in this application is warranted.

Aged↗
PubMed1997

Mechanical stimulation of tissue repair in the hydraulic bone chamber.

A hydraulically activated bone chamber model was utilized to investigate cellular and microstructural mechanisms of mechanical adaptation during bone repair. Woven trabecular bone and fibrotic granulation tissue filled the initially empty chambers by 8 weeks postimplantation into canine tibial and femoral metaphyses. Without mechanical stimulation, active bone remodeling to lamellar trabecular bone and reconstitution of marrow elements were observed between 8 and 24 weeks. In subsequent loading studies, the hydraulic mechanism was activated on one randomly chosen side of 10 dogs following 8 weeks of undisturbed bone repair. The loading treatment applied an intermittent compressive force (18 N, 1.0 Hz, 1800 cycles/day) for durations of a few days up to 12 weeks. Stereological analysis of three-dimensional microcomputed tomography images revealed an increase in trabecular plate thickness and connectivity associated with the loaded repair tissue microstructure relative to unloaded contralateral controls. These microstructural alterations corresponded to an over 600% increase in the apparent modulus of the loaded bone tissue. A significant increase in the percentage of trabecular surfaces lined by osteoblasts immunopositive for type I procollagen after a few days of loading provided further evidence for mechanical stimulation of bone matrix synthesis. The local principal tissue strains associated with these adaptive changes were estimated to range from approximately -2000 to +3000 mustrain using digital image-based finite element methods. This study demonstrates the sensitivity of bone tissue and cells to a controlled in vivo mechanical stimulus and identifies microstructural mechanisms of mechanical adaptation during bone repair. The hydraulic bone chamber is introduced as an efficient experimental model to study the effects of mechanical and biological factors on bone repair and regeneration.

Animals↗
PubMed1996

ORK1, a potassium-selective leak channel with two pore domains cloned from Drosophila melanogaster by expression in Saccharomyces cerevisiae.

A K+ channel gene has been cloned from Drosophila melanogaster by complementation in Saccharomyces cerevisiae cells defective for K+ uptake. Naturally expressed in the neuromuscular tissues of adult flies, this gene confers K+ transport capacity on yeast cells when heterologously expressed. In Xenopus laevis oocytes, expression yields an ungated K(+)-selective current whose attributes resemble the "leak" conductance thought to mediate the resting potential of vertebrate myelinated neurons but whose molecular nature has long remained elusive. The predicted protein has two pore (P) domains and four membrane-spanning helices and is a member of a newly recognized K+ channel family. Expression of the channel in flies and yeast cells makes feasible studies of structure and in vivo function using genetic approaches that are not possible in higher animals.

Amino Acid Sequence↗
PubMed1996

Stimulation of new bone formation by direct transfer of osteogenic plasmid genes.

Degradable matrices containing expression plasmid DNA [gene-activated matrices (GAMs)] were implanted into segmental gaps created in the adult rat femur. Implantation of GAMs containing beta-galactosidase or luciferase plasmids led to DNA uptake and functional enzyme expression by repair cells (granulation tissue) growing into the gap. Implantation of a GAM containing either a bone morphogenetic protein-4 plasmid or a plasmid coding for a fragment of parathyroid hormone (amino acids 1-34) resulted in a biological response of new bone filling the gap. Finally, implantation of a two-plasmid GAM encoding bone morphogenetic protein-4 and the parathyroid hormone fragment, which act synergistically in vitro, caused new bone to form faster than with either factor alone. These studies demonstrate for the first time that repair cells (fibroblasts) in bone can be genetically manipulated in vivo. While serving as a useful tool to study the biology of repair fibroblasts and the wound healing response, the GAM technology may also have wide therapeutic utility.

Animals↗
PubMed1996

Type-I collagen mutation compromises the post-yield behavior of Mov13 long bone.

Despite recent advances in our understanding of the molecular basis of skeletal fragility, little is known about how these molecular alterations lead to whole bone brittleness. In the current study, we investigated the relationship between a type-I collagen mutation and post-yield behavior of whole bone in Mov13 transgenic mice by considering tissue-level organizational issues known to be important for normal bone fracture. Mechanical assays revealed that the post-yield deflection of Mov13 femurs was reduced by 61% relative to littermate controls. Fractographic images revealed that lamellar interfaces which were important for dissipating energy during the failure process of control femurs, were not effective in Mov13 mice. Further investigation revealed that a 22% reduction in bone collagen content, a 2-fold increase in tissue porosity, and significant alterations in collagen organization interfered with normal energy dissipation mechanisms of Mov13 microstructure. Collectively, the results provided the first evidence that the reduced ductility associated with a type-I collagen mutation was mediated by alterations in intermediate structures that normally contribute to the post-yield behavior of cortical bone. The results suggest that, to better understand the pathogenesis of skeletal fragility, it is important to consider the effects of molecular alterations on higher-level structures, particularly those structures that contribute to the failure mechanisms in normal bone.

Animals↗
PubMed1996

Local expression of human growth hormone in bone results in impaired mechanical integrity in the skeletal tissue of transgenic mice.

The effect of local production of human growth hormone on murine cortical bone was investigated using a transgenic mouse model. Femora and humeri from human growth hormone transgenic mice and littermate control mice were obtained, and the geometrical, biomechanical, compositional, and histomorphometric properties of all specimens were determined. The goals were to investigate the effects of local expression of human growth hormone on skeletal integrity, including the functional geometry of long bone and its related structural and mechanical behavior, as well as tissue composition and integrity. As expected, local production of human growth hormone by osteoblasts indeed resulted in longer femora with significantly greater mid-diaphyseal cross-sectional geometry in the transgenic mice (16% increase in cross-sectional area and 29% increase in bending moments of inertia). However, the significant increase in geometry was not associated with a proportional increase in bending stiffness and other structural properties, which suggested that the mechanical properties of the cortical bone tissue may have been inferior. Microspecimen bending tests verified this prediction, given that transgenic cortical bone tissue had significantly lower apparent elastic modulus and ultimate strength (52 and 68%, respectively, of control values). These defects in the whole bone structural and tissue mechanical properties of transgenic specimens were associated with a smaller fraction of ash, larger fractions of woven bone and cartilage islands, and greater porosity in the mid-diaphyseal cortices. These results suggest that local production of human growth hormone by osteoblasts is indeed anabolic for bone, but at the expense of bone tissue integrity.

Adaptation, Physiological↗
PubMed1996

Relative effects of wound healing and mechanical stimulus on early bone response to porous-coated implants.

We hypothesized that early bone adaptation to well fixed porous-coated implants is influenced more by wound healing than by mechanical loading. To test this hypothesis, two groups of dogs with identical, hydraulically controlled porous-coated implants interference fit within distal femoral trabecular bone were used. One group had no load: the other had 35 N of load applied to the implants. At 5 weeks after surgery, the resulting adaptation of bone around the implants was quantified on a cellular basis by cytochemical analysis of type-I procollagen synthesis and on a structural basis using three-dimensional micro-computed tomography imaging. The percentage of trabecular surfaces covered by osteoblasts expressing type-I procollagen was significantly increased in bone surrounding the implant in both groups compared with contralateral control bone tissue. There was no difference between the groups with no load or 35 N of load. In addition, measures of trabecular bone structure did not differ significantly between the load and no-load groups. Taken together, these results suggest that wound healing plays a much greater role in the early response of bone to well fixed porous-coated implants than does mechanical stimulus.

Animals↗
PubMed1996

Predictive value of proximal femoral bone densitometry in determining local orthogonal material properties.

Models which are based on non-invasive bone measurements may in the future be able to successfully identify individual subjects at an increased risk for hip fracture; thus, we designed a study to determine the usefulness of dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) in predicting the local material properties of human proximal femoral cancellous bone. There has been some disagreement in the scientific literature regarding appropriate predictive models for local material properties of cancellous bone. We sought to confirm that density-mechanical property relationships were consistent from subject to subject, and that three-dimensional QCT measurements were stronger predictors of mechanical properties than two-dimensional DXA results. Linear and power fit relationships between these densitometric measures and material properties were also examined to determine which were more appropriate. Bone cubes from specific regions of highly oriented trabeculae were analyzed separately to determine if cube orientation had an effect on mechanical properties independent of bone density. Ten pairs of ex vivo femurs (five male, five female; age 30-93, mean age 62) were prepared such that specific anatomic planes were visible radiographically. Both QCT and DXA measurements were made on all 20 femurs. Cancellous bone cubes were obtained proceeding along two distinct directions from the proximal end of each femur pair. Unexpectedly, the density-modulus relationships among these ten donors were found to be significantly different at p <0.01 (83 percent of the tests were different at p <0.0001). Density-strength regressions were also significantly different at p <0.01, but this effect was not as consistent nor as statistically significant. In general, the QCT method did not produce predictions of local cancellous bone material properties superior to the DXA method. The linear and power fit models appeared to produce consistent results, with neither being obviously more advantageous. These density measurements explained at best 30-40 percent of the variance in modulus and 50-60 percent of the variance in ultimate stress. The orientation of cancellous cubes in the principal compressive trabeculae region was a significant contributor to mechanical properties (p= 0.0001) independent of bone density. This finding was not as dramatic in the femoral neck cancellous bone region.

Absorptiometry, Photon↗
PubMed1996

Ion channels: structural basis for function and disease.

Ion channels are ubiquitous proteins that mediate nervous and muscular function, rapid transmembrane signaling events, and ionic and fluid balance. The cloning of genes encoding ion channels has led to major strides in understanding the mechanistic basis for their function. These advances have shed light on the role of ion channels in normal physiology, clarified the molecular basis for an expanding number of diseases, and offered new direction to the development of rational therapeutic interventions.

Action Potentials↗
PubMed1996

MinK residues line a potassium channel pore.

MinK has neither the P region nor signature sequence that characterizes pore-forming subunits of all known K+ channels. A specific minK region has now been identified that affects external blockade by 2 common probes of K+ channel pores. When mutated to cysteine, residues in this region render minK susceptible to covalent blockade by methanethiosulfonate ethylsulfonate and alter reversible inhibition by tetraethylammonium. The 2 blockers are found to share overlapping binding site determinants and to interact. Since inhibition by external tetraethylammonium is sensitive to voltage and to the internal concentration of permeant ions, we argue that tetraethylammonium blocks by occluding the external end of a water-filled transmembrane pore. These findings support the view that minK is directly involved in forming a K+-selective ion conduction pathway.

Molecular Structure↗
PubMed1996

Oxytetracycline-induced nephrotoxicosis in dogs after intravenous administration for experimental bone labeling.

Tetracyclines have been used as in vivo indicators of new bone formation because they form complexes with mineral at bone-forming surfaces. Four of 12 dogs in a bone-labeling study developed clinical signs of renal disease (vomiting, diarrhea, dehydration, and azotemia) within 1 to 2 days of receiving oxytetracycline at a bone-labeling dose of 25 mg/kg of body weight, once daily for 2 consecutive days. To delineate the relationship between oxytetracycline administration and renal damage, six dogs were given the bone-labeling dose intravenously and were subsequently evaluated by determination of clinical signs, serum biochemical analysis, urinalysis, and histologic examination (experiment 1). Drug administration was modified in the five dogs remaining in the bone-labeling orthopedic study. These dogs received the oxytetracycline dose as a slow intravenous infusion diluted with 250 ml of lactated Ringer's solution (experiment 2). All six dogs of experiment 1 developed persistent isosthenuria within 2 days of receiving the bone-labeling dose of oxytetracycline. Clinical illness (three of six dogs) was associated with azotemia, creatinemia, and hyperphosphatemia. All dogs had multifocal, mild to moderate flattening of renal tubular epithelium, characteristic of nephrosis. None of the dogs of experiment 2 developed any clinical indications of renal disease, and the only biochemical abnormality was isosthenuria in two of the five dogs. Thus the development of clinical signs and biochemical abnormalities associated with the intravenous administration of oxytetracycline was obviated by the slow administration of a dilution of the calculated bone-labeling dose of the antibiotic.

Animals↗
PubMed1995

A new family of outwardly rectifying potassium channel proteins with two pore domains in tandem.

Potassium channels catalyse the permeation of K+ ions across cellular membranes and are identified by a common structural motif, a highly conserved signature sequence of eight amino acids in the P domain of each channel's pore-forming alpha-subunit. Here we describe a novel K+ channel (TOK1) from Saccharomyces cerevisiae that contains two P domains within one continuous polypeptide. Xenopus laevis oocytes expressing the channel exhibit a unique, outwardly rectifying, K(+)-selective current. The channel is permeable to outward flow of ions at membrane potentials above the K+ equilibrium potential; its conduction-voltage relationship is thus sensitive to extracellular K+ ion concentration. In excised membrane patches, external divalent cations block the channel in a voltage-dependent manner, and their removal in this configuration allows inward channel current. These attributes are similar to those described for inwardly rectifying K+ channels, but in the opposite direction, a previously unrecognized channel behaviour. Our results identify a new class of K+ channel which is distinctive in both its primary structure and functional properties. Structural homologues of the channel are present in the genome of Caenorhabditis elegans.

Amino Acid Sequence↗
PubMed1995

Skeletal repair by in situ formation of the mineral phase of bone.

A process has been developed for the in situ formation of the mineral phase of bone. Inorganic calcium and phosphate sources are combined to form a paste that is surgically implanted by injection. Under physiological conditions, the material hardens in minutes concurrent with the formation of dahllite. After 12 hours, dahllite formation was nearly complete, and an ultimate compressive strength of 55 megapascals was achieved. The composition and crystal morphology of the dahllite formed are similar to those of bone. Animal studies provide evidence that the material is remodeled in vivo. A novel approach to skeletal repair is being tested in human trials for various applications; in one of the trials the new biomaterial is being percutaneously placed into acute fractures. After hardening, it serves as internal fixation to maintain proper alignment while healing occurs.

Animals↗
PubMed1995

Static and fatigue failure properties of thoracic and lumbar vertebral bodies and their relation to regional density.

This study investigated (1) whether a characterization of the macroscopic architecture within the vertebral centrum would improve predictions of vertebral strength, (2) if regions in the centrum where least bone loss with age occurs are more predictive of vertebral strength, and (3) whether different patterns of the macroscopic architecture are predictive of static as compared to fatigue strength. To characterize the vertebral macroscopic architecture, a regional bone mineral density (rBMD) technique was used that estimated the cancellous density distribution (in 18 specific regions of the vertebral centrum) for vertebrae T7-L4, from spines of 20 female cadavers. Static and fatigue failure properties of whole vertebrae were obtained, and predictive models of static and fatigue failure properties of whole vertebrae were examined. We found that (1) vertebral failure properties were better predicted by combinations of vertebral regional cancellous density (multiple linear regressions) rather than by any individual region of cancellous density alone (simple linear regressions); (2) models using regions of density that demonstrated minimum decline with age [from the data of Flynn and Cody (Calcif. Tissue Int. 53, S170-S175 (1993))] resulted in better correlations with ex vivo vertebral static failure properties than models using density regions that showed maximum decline with age, and (3) static and fatigue characteristics required different density regions to reach significance. (A comparison of models predictive of static and fatigue failure properties revealed that anterior density regions were most often included in predictive models of the static properties while posterior regions were more predictive of the fatigue properties).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗