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Biomedical subjects

K A Thomas

Publications and source records attributed to K A Thomas.

At least 19 recordsLinked to original sources
PubMed1995

Purification and characterization of a naturally occurring vascular endothelial growth factor.placenta growth factor heterodimer.

Vascular endothelial growth factor (VEGF) is a potent and selective mitogen for endothelial cells that is angiogenic in vivo and induced by hypoxia. A homologous protein, placenta growth factor (PlGF), is also reported to be mitogenic for endothelial cells in culture. The rat GS-9L glioma cell line produces not only VEGF homodimers but also PlGF homodimers and a novel heterodimer composed of VEGF and PlGF subunits. All three dimeric forms were purified to apparent homogeneity, and their structures and mitogenic activities were compared. VEGF.PlGF heterodimers are vascular endothelial cell mitogens nearly as potent as VEGF homodimers. Therefore, some of the biological activities attributed to VEGF homodimers might be mediated by VEGF.PlGF heterodimers. In contrast, pure PlGF homodimers are mitogenic for endothelial cells only at high, possibly non-physiologic concentrations; thus the biological relevance of their mitogenic activity for these cells is not obvious. However, the existence of not only homodimers but also heterodimers clearly extends the similarity between the VEGF/PlGF and the homologous platelet-derived growth factor systems.

Amino Acid Sequence↗
PubMed1995

Acidic fibroblast growth factor stimulates motor and sensory axon regeneration after sciatic nerve crush in the rat.

A time course study in untreated male Sprague-Dawley rats showed that there was no significant difference in the rate of regeneration of motor and sensory axons after a crush injury. Acidic fibroblast growth factor, given topically directly to the site of the crush injury (osmotic minipump for three days) or systemically (i.v. once daily for three days), stimulated the regeneration of motor axons and myelinated sensory axons in the sciatic nerve of the rat. Dose-dependent increases in regeneration distance were seen after 3.6, 36 or 360 ng/day were applied locally and 3 or 10 micrograms/kg per day were given systematically. The greatest effects were achieved with 36 ng/day locally or 10 micrograms/kg per day systematically, when the increase in regeneration distance over three days compared to untreated rats was 47% and 48%, respectively. Administration of heparin vehicle had no significant effect on regeneration. We conclude that since a crush injury has little effect on the endoneurial tubes and supporting cells, the stimulatory effects of acidic fibroblast growth factor on peripheral nerve regeneration seen in this study are likely to be due to a direct acceleration of axonal extension. This is in contrast with the axonal regeneration that occurs across a gap after nerve transection, where axonal extension may be secondary to stimulatory effects on non-neuronal cells providing a supporting "bridge" across the gap. These results suggest that acidic fibroblast growth factor may be clinically useful in the treatment of peripheral neuropathy in man, particularly since systemic treatment for short periods may be effective.

Animals↗
PubMed1995

Effects of indomethacin on biologic fixation of porous-coated titanium implants.

The effect of perioperative administration of indomethacin on attachment strength and bone growth into porous-coated titanium implants was evaluated in the canine transcortical plug model. Various drug administration protocols simulating clinical use of indomethacin were studied. These included chronic treatment (starting 2 weeks prior to surgery), treatment immediately after surgery, and treatment 3, 6, 9, and 18 weeks following surgery. Indomethacin therapy was continued until sacrifice at 3, 6, 12, 18, or 24 postoperative weeks. Push-out testing was performed to determine the maximum bone-implant interface shear strength, and quantitative histologic analysis was used to determine percentage of bone ingrowth. When indomethacin was administered chronically or immediately after surgery, a statistically significant decrease in bone-implant interface attachment strength was seen at 3 postoperative weeks but not at later periods. No adverse effect was observed in any group after the 3-week period. Quantitative histologic analysis demonstrated no significant differences in percentage bone ingrowth among any of the treatment protocols at 3 or 6 weeks after surgery. No significant difference was observed between any of the groups at 18 or 24 weeks. The results of this study suggest that perioperative administration of indomethacin does not significantly affect attachment strength or bone ingrowth into porous-coated implants except at early periods, in which cases a transient decrease in attachment strength occurs.

Animals↗
PubMed1995

Biorhythms in infants and role of the care environment.

All physiologic functions demonstrate cyclic activity. Infant development includes maturation of biorhythms. Two basic changes in biorhythm include establishment of circadian rhythm and day-night pattern. Biorhythms are driven by internal pacemakers yet are highly susceptible to environmental influences. Sleep-wake pattern and body temperature rhythm are two examples of infant biorhythms that demonstrate significant change with development. Biorhythm is the scientific basis for interventions (such as cycled lighting, feeding schedule, and caregiving pattern) aimed at improving the fit between infant and the environment.

Circadian Rhythm↗
PubMed1995

Acidic fibroblast growth factor accelerates dermal wound healing in diabetic mice.

Acidic fibroblast growth factor (aFGF) is a potent mitogenic and chemotactic agent for vascular endothelial cells, dermal fibroblasts, and epidermal keratinocytes, the principal cellular constituents of skin. To explore its potential to heal chronic dermal wounds, we applied pure recombinant human aFGF topically to full-thickness excisional injuries in healing-impaired genetically diabetic mice. Transformation of the nonlinear percent initial wound areas as a function of time to linear rates of tissue ingrowth from the original wound edges showed that aFGF increased wound closure in a dose-dependent manner. Optimal 3-micrograms/cm2 doses of aFGF nearly tripled the linear rate of healing. The median time to complete closure decreased from 46 d in vehicle-treated wounds to only 16 d in those treated with aFGF. Histomorphometric analyses established that aFGF increased granulation tissue formation and reepithelialization throughout healing. Vehicle- and aFGF-treated wounds appeared to be histologically equivalent by the time of closure. Therefore, aFGF has potential therapeutic applications for promoting healing of dermal ulcers, especially in healing-impaired individuals.

Animals↗
PubMed1995

The effect of operative fit and hydroxyapatite coating on the mechanical and biological response to porous implants.

UNLABELLED: Femoral intramedullary implants were constructed by threading 4.0-millimeter-thick disks with a titanium-alloy (Ti-6Al-4V) porous bead coating onto a two-millimeter-diameter threaded rod. Each porous-coated disk, which was 6.0, 8.0, 9.0, or 10.0 millimeters in diameter, was separated by a two-millimeter-thick acrylic disk with a diameter of ten millimeters. Implants with and without a hydroxyapatite coating of twenty-five micrometers were inserted into fifteen skeletally mature adult mongrel dogs. The femoral canal was sequentially reamed bilaterally to a ten-millimeter diameter, resulting in uniform initial implant-bone interface gaps of 0.0, 0.5, 1.0, and 2.0 millimeters. Each animal received paired hydroxyapatite-coated and uncoated implants. Three animals each were killed at four, eight, twelve, twenty-four, and fifty-two weeks after the implantation. The harvested femora were sectioned through the acrylic spacers, transverse to the long axis, to produce individual push-out test specimens for mechanical testing. Characteristics of interface attachment were determined with test fixtures that supported the surrounding bone to within 150 micrometers of the interface. Histological sections were prepared, and the amount of bone within the porous structure and the amount of the original gap that was filled with new bone were quantified with a computerized video image-analysis system. Mechanical attachment strength and bone ingrowth were found to increase with the time after implantation and with a decrease in the size of the gap. Placement of the implant in proximal (cancellous) compared with distal (cortical) locations had no significant effect on the strength of attachment, bone ingrowth, or gap-filling. However, implants with a large initial gap (1.0 or 2.0 millimeters) demonstrated greater attachment strength in cancellous bone than in cortical bone. With a few exceptions, hydroxyapatite-coated implants with an initial gap of 1.0 millimeter or less demonstrated significantly increased mechanical attachment strength and bone ingrowth at all time-periods. Interface attachment strengths were positively correlated with bone ingrowth, the time after implantation, the use of a hydroxyapatite coating, and decreasing initial gap size. CLINICAL RELEVANCE: Initial implant-bone apposition is thought to be a prerequisite for good biological fixation. This apposition is often not achieved because of the design of the implant or instruments and the operative technique. Poor initial fit during the operation may decrease the longevity of the implant. The results of the present study indicate that attachment strength and bone ingrowth are significantly affected by gaps in the interface, particularly those of more than 1.0 millimeter.(ABSTRACT TRUNCATED AT 400 WORDS)

Alloys↗
PubMed1995

The effects of the interosseous membrane and partial fibulectomy on loading of the tibia: a biomechanical study.

The biomechanical basis for the treatment of delayed union of tibial fractures by partial fibulectomy has yet to be fully evaluated. To gain further insight into this problem, nine intact cadaveric lower extremities were instrumented with strain gauges on the surfaces of the tibia and fibula. The limbs were then subjected to axial loading with the ankle and subtalar joints placed in multiple positions. The specimens were loaded either through the distal femur or by direct loading of the tibial plateau. All specimens were first tested intact then after sectioning of the interosseous membrane and finally after partial fibulectomy. It was shown that during loading of the leg, the primary effects of the interosseous membrane were to stabilize the fibula and constrain its posterolateral bending. The fibular strains were not reduced to zero following sectioning of the interosseous membrane. Tibial strains measured on the anteromedial and anterolateral surfaces were consistently in relative tension, indicating a posterior bending force (anterior bowing) of the tibia. After partial fibulectomy, strains on these surfaces became relatively more compressive. With the ankle and subtalar joints in neutral position (0 degree flexion, 0 degree inversion/eversion) the strains on the anterior surface averaged approximately 10% more compressive relative to the intact condition. Tibial strains were observed to vary with the position of the ankle and subtalar joints. The fact that the anteromedial and anterolateral tibia surfaces were always in tension may explain why partial fibulectomy has not proved to be a uniformly successful treatment method for delayed union of the tibia. Furthermore, it points to the important role of "fracture personality" in the selection of treatment.

Aged↗
PubMed1994

Effects of bone mineral density on pedicle screw fixation.

STUDY DESIGN: In an attempt to evaluate the effects of bone mineral density on the quality of fixation of pedicle screws in the lumbar spine, the axial pullout force was determined and compared in normal and osteoporotic human lumbar spines. OBJECTIVES: Four techniques of screw hole preparation were evaluated. Two pedicle screw/offset laminar hook constructs also were evaluated to determine whether the adjunct fixation of the laminar hooks would improve quality of fixation to a level sufficient to allow their use in the osteoporotic lumbar spine. METHODS: Pedicle screws were inserted by one of the listed techniques into fresh frozen cadaveric human spines. The fixation strength then was evaluated by pullout on a uniaxial testing frame. RESULTS: Bone mineral density was a strong influence on axial pullout force. In normal bone, the method of screw hole preparation did not significantly affect the quality of fixation. However, in the osteoporotic spine, either an untapped screw hole or the tapping of a screw hole with a 5.5 mm tap improved the pullout force a statistically significant amount (P < 0.003). Also, a pedicle screw with offset hooks at two adjacent levels improved the fixation significantly, increasing the pullout force to twice the expected value. CONCLUSION: Pedicle screw pullout strength was highly correlated with bone mineral density. A 5.5 mm tap or preparation with a ganglion knife improved pullout strength. Use of pedicle screws in conjunction with laminar hooks at two levels improved pullout strength.

Biomechanical Phenomena↗
PubMed1994

Specificity of vascular endothelial cell growth factor receptor ligand binding domains.

Vascular endothelial cell growth factor binds with high affinity to FLT and KDR, two homologous tyrosine kinase receptors expressed on vascular endothelial cells. Placental growth factor, a vascular endothelial cell growth factor homologue, also binds with high affinity to the extracellular domains of FLT but not to the extracellular region of KDR. Vascular endothelial cell growth factor binds competitively with placental growth factor to the extracellular ligand binding domains of FLT, indicating that both ligands probably complex to overlapping or identical regions of this receptor.

Binding Sites↗
PubMed1994

Evaluation of methods of internal fixation of transverse patella fractures: a biomechanical study.

Biomechanical testing was performed to evaluate five techniques of internal fixation of transverse patella fractures. Using cadaveric lower extremities, transverse osteotomies of the patella were performed, and the simulated fractures were fixed with the following techniques: the modified tension band, anterior tension band with a supplemental cerclage wire (the Pyrford technique), tension band with cancellous bone screws, Pyrford technique with cancellous screws, and cancellous screws alone. The fixation techniques were evaluated by measuring the separation of the fracture fragments during loading to produce a physiologic range of motion (90 degrees flexion to full extension). All techniques functioned adequately, with no fracture gap exceeding 1 mm. The tension band with screws technique performed significantly better than did the modified tension band, with an average fracture gap approximately half that of the traditional modified tension band technique. Mechanically, the addition of the screws to the tension band techniques reduces fracture separation by providing compression throughout the range of motion and by resisting the tensile loading during terminal extension.

Aged↗
PubMed1994

Induction of vascular endothelial growth factor expression by prostaglandin E2 and E1 in osteoblasts.

PGE1 and PGE2 are potent stimulators of bone formation. Osteogenesis is strongly dependent on angiogenesis. Vascular endothelial growth factor (VEFG), a secreted endothelial cell-specific mitogen, has been implicated in physiological and pathological angiogenesis. The aim of this study was to examine the possible role of VEGF in PG stimulation of bone formation. We found that in rat calvaria-derived osteoblast-enriched cells and in the osteoblastic RCT-3 cell line PGE2 and E1 increased VEGF mRNA and protein levels. The increased expression of VEGF mRNA produced by PGE2 was rapid (maximal at 1 h), transient (declined by 3 h), potentiated by cycloheximide, and abolished by actinomycin D. PGE2 had no effect on VEGF mRNA stability, suggesting transcriptional regulation of VEGF expression by PGF2. Rp-cAMP, a cAMP antagonist, suppressed VEGF mRNA induced by PGE2, indicating cAMP mediation. The upregulation of VEGF expression by PGE2 in the preosteoblastic RCT-1 cells was potentiated by treatment with retinoic acid, which induces the differentiation of these cells. The upregulation of VEGF mRNA by PGE2 was inhibited by dexamethasone treatment. In addition, Northern blot analysis showed that VEGF mRNA is expressed in adult rat tibia. In summary, we documented, for the first time, the expression of VEGF in osteoblasts and in bone tissue. Stimulation of VEGF expression by PGs and its suppression by glucocorticoids, which, respectively, stimulate and suppress bone formation, strongly implicate the involvement of VEGF in bone metabolism.

Alprostadil↗
PubMed1994

Hydroxyapatite coatings.

A series of investigations over the past several years has evaluated a number of implant materials with and without plasma-sprayed hydroxyapatite (HA) coatings for use in load-bearing implant applications. HA-coated implants have exhibited greater interface shear attachment characteristics when compared to uncoated implants; these results have been demonstrated with dense (flat), porous-coated, and macrotextured implant surfaces. Maximum attachment strength also was found to occur within a shorter period of time postoperatively with the HA-coated samples, indicating a more rapid tissue adaptation to the implant surfaces. Plasma-sprayed HA coatings provide an osteophilic and osteoconductive surface that increases both the bone-implant attachment strength, as well as the rate of bone adaptation to the HA-coated implant surface.

Biomechanical Phenomena↗
PubMed1994

Enhanced spino-pelvic fixation for segmental spinal instrumentation: a preliminary biomechanical evaluation.

A new method for spino-pelvic fixation of Luque rods was developed and biomechanically evaluated on cadaveric specimens. The technique is surgically simpler and faster than the Galveston technique because it does not require the complex three-dimensional bending of rods to conform to the medullary cavity of the iliac wings. Spines were tested in axial compression in both bilateral and unilateral ischial weight bearing in the intact condition, instrumented with the new technique, and instrumented with the Galveston technique. Compared to the intact spine, the technique increased bilateral average stiffness by 131% and unilateral average stiffness by 192%. Compared directly to the Galveston technique, the new method exhibited increased average stiffness of 15% in bilateral and 11% in unilateral ischial weight bearing. The new method combines the advantages of a simpler and faster surgical procedure than the Galveston technique with enhanced spino-pelvic fixation with the potential to decrease migration of rods relative to each other and the pelvis.

Aged↗
PubMed1993

Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor.

Vascular endothelial cell growth factor, a mitogen selective for vascular endothelial cells in vitro that promotes angiogenesis in vivo, functions through distinct membrane-spanning tyrosine kinase receptors. The cDNA encoding a soluble truncated form of one such receptor, fms-like tyrosine kinase receptor, has been cloned from a human vascular endothelial cell library. The mRNA coding region distinctive to this cDNA has been confirmed to be present in vascular endothelial cells. Soluble fms-like tyrosine kinase receptor mRNA, generated by alternative splicing of the same pre-mRNA used to produce the full-length membrane-spanning receptor, encodes the six N-terminal immunoglobulin-like extracellular ligand-binding domains but does not encode the last such domain, transmembrane-spanning region, and intracellular tyrosine kinase domains. The recombinant soluble human receptor binds vascular endothelial cell growth factor with high affinity and inhibits its mitogenic activity for vascular endothelial cells; thus this soluble receptor could act as an efficient specific antagonist of vascular endothelial cell growth factor in vivo.

Alternative Splicing↗
PubMed1993

Roentgenographic procedure for selecting proximal femur allograft for use in revision arthroplasty.

A roentgenographic scoring system was developed to help orthopaedic surgeons and bone banks estimate the quality of bone stock in proximal femoral allografts intended to use in revision arthroplasty. This system scores a standardized anteroposterior roentgenograph of the proximal femur using four indices representing morphological features of cancellous and cortical bone known to be clinically associated with bone strength. The indices were combined to give a weighted score, which was thought to reflect the ability of a bone to carry in vivo loads. Thirty bones were evaluated for bone mineral density using dual-photon absorptiometry. They were then sent to another institution and evaluated using the newly devised roentgenographic scoring system. The results showed that the bone score roentgenographic method is a reasonable technique for selecting allograft femurs for transplantation. This roentgenographic technique and scoring system has now been packaged into kits and is available to orthopaedic surgeons and bone banks for evaluating bone stock quality in proximal femoral allografts intended for transplantation.

Absorptiometry, Photon↗
PubMed1992

Hydroxylapatite coating of porous implants improves bone ingrowth and interface attachment strength.

The effect of a plasma-sprayed hydroxylapatite (HA) coating on the degree of bone ingrowth and interface shear attachment strength was investigated using a canine femoral transcortical implant model. Cylindrical implants were fabricated by sintering spherical Co-Cr-Mo particles 500-710 microns in diameter; the nominal implant dimensions were 5.95 +/- 0.05 mm diameter by 18 mm in length. One half of each implant was coated with hydroxylapatite, 25-30 microns in thickness, by a plasma-spray technique. Using strict aseptic technique, the implants were placed through both femoral cortices into defects approximately 0.05 mm undersized. After 2, 4, 6, 8, 12, 18, 26, and 52 weeks, the implants were harvested and subjected to mechanical pullout testing and undecalcified histologic evaluation. The application of the HA coating to porous implants enhanced both the amount of bone ingrowth and the interface attachment strength at all time periods. These differences were statistically significant for the percent of bone ingrowth at the 4-, 6-, 12-, 18-, 26-, and 52-week time periods, and interface shear strength values were significantly different at the 6-, 8-, 12-, 18-, and 26-week time periods. The rate of development of interface strength and bone ingrowth was also more rapid for the HA-coated implants. No evidence of any disruption, mechanical failure, or biologic resorption of the HA coating was observed. The results of the present study--demonstrating a beneficial effect of the HA coating at all time periods--are believed to be due to the use of paired comparisons, which allow assessment of subtle differences that might otherwise have been obscured by normal biological variability.

Analysis of Variance↗