Biomedical subjects

Kevin A Thomas

Publications and source records attributed to Kevin A Thomas.

16 recordsLinked to original sources

PubMed2006

Essential and overlapping roles for laminin alpha chains in notochord and blood vessel formation.

Laminins are major constituents of basement membranes and have wide ranging functions during development and in the adult. They are a family of heterotrimeric molecules created through association of an alpha, beta and gamma chain. We previously reported that two zebrafish loci, grumpy (gup) and sleepy (sly), encode laminin beta1 and gamma1, which are important both for notochord differentiation and for proper intersegmental blood vessel (ISV) formation. In this study we show that bashful (bal) encodes laminin alpha1 (lama1). Although the strongest allele, bal(m190), is fully penetrant, when compared to gup or sly mutant embryos, bal mutants are not as severely affected, as only anterior notochord fails to differentiate and ISVs are unaffected. This suggests that other alpha chains, and hence other isoforms, act redundantly to laminin 1 in posterior notochord and ISV development. We identified cDNA sequences for lama2, lama4 and lama5 and disrupted the expression of each alone or in mutant embryos also lacking laminin alpha1. When expression of laminin alpha4 and laminin alpha1 are simultaneously disrupted, notochord differentiation and ISVs are as severely affected as sly or gup mutants. Moreover, live imaging of transgenic embryos expressing enhanced green fluorescent protein in forming ISVs reveals that the vascular defects in these embryos are due to an inability of ISV sprouts to migrate correctly along the intersegmental, normally laminin-rich regions.

Animals↗

PubMed2006

Characterization of a faster resorbing polymer after real time aging.

This study evaluated the in vitro strength retention and polymer characteristics of specimens made from commercially available 85:15 poly(D,L-lactide-co-glycolide). Test samples included dogbone tensile specimens with a nominal thickness of either 0.75 and 1.0 mm, which were machined from compression-molded sheets, and screws with a major diameter of 2.71 mm and minor diameter of 2.14 mm, which were manufactured by injection molding. All samples were sterilized by e-beam irradiation prior to in vitro aging following a standard methodology. Mechanical testing and polymer analysis were performed at time zero and weekly up to 15 weeks of real time aging. The time zero maximum tensile strength of the 0.75 mm dogbone specimens averaged 55.86 +/- 0.72 MPa. The 1.0-mm dogbone specimens tested at time zero had an average maximum tensile strength of 34.55 +/- 0.36 MPa. The 0.75-mm and 1.0-mm thick dogbone specimens exhibited a controlled decrease in their tensile strength. The initial shear strength of the injection-molded screws was 32.86 +/- 4.15 MPa. After 3 weeks of real time in vitro aging, the screws maintained approximately 70% of their initial (time zero) strength. The inherent viscosity and molecular weight (Mw) at time zero averaged approximately 0.9 dL/g and 98,000 g/mol respectively, and decreased at similar rates for both dogbones and screws. These results demonstrate a controlled, rapid degradation in the mechanical properties of 85:15 poly(D,L-lactide-co-glycolide) material, with sufficient strength for pediatric craniofacial applications.

Bone Substitutes↗

PubMed2006

Evaluation of a bioresorbable polylactide sheet for the reduction of pelvic soft tissue attachments in a porcine animal model.

In an adult porcine model, the effectiveness of a bioresorbable film to minimize soft tissue attachment to the pelvic viscera was evaluated at 4-week and 12-week endpoints. Following a transperitoneal laparotomy through a midline incision, the bladder and uterus were abraded in all animals to promote soft tissue attachment to the viscera. Control animals received no further treatment. The experimental group animals were treated with bioresorbable polylactide (PLa) sheets, 0.02 mm thick, one between the bladder and the abdominal wall, and a second sheet between the bladder and the uterus. Quantitative assessment of the severity and location of soft tissue attachments, and qualitative histologic assessment were performed at 4 and 12 weeks post-operatively. Statistically significant differences in the quantitative soft tissue attachment scores were observed in comparing the PLa film treated animals versus the control animals, at both the 4-week and 12-week time points. In the control animals, the formation of numerous thick fibrous bands was observed at both time points. Histology revealed no adverse reaction to the bioresorbable PLa barrier film. The bioresorbable PLa sheet provided an effective barrier between adjacent anatomical structures and minimized soft tissue attachments to the device when in contact with the viscera as compared to the control groups. Surgical dissection planes between the abdominal wall and adjacent soft tissues were maintained with the use of the PLa sheet at both time points.

Absorbable Implants↗

PubMed2005

Strength retention of 70:30 poly(L-lactide-co-D,L-lactide) following real-time aging.

This study evaluated the in vitro strength retention and polymer characteristics of plates and screws made from commercially available 70:30 poly(L-lactide-co-D,L-lactide) over a 2-year time period. Test samples included three routine manufacturing lots each of plates (1.2 mm thick, 41.70 mm long, with 2.5-mm holes), which were machined from compression-molded sheets, and screws (2.4-mm major diameter and 1.86-mm minor diameter), which were manufactured by injection molding. All samples were sterilized by e-beam irradiation prior to in vitro aging following a standard methodology. Mechanical testing and polymer analysis was performed after 0, 6, 13, 26, 39, 52, 65, 78, and 104 weeks. The initial (time zero) tensile strength of the plates averaged 33.2+/-1.9 MPa; the plates retained 100% of this strength at 6 weeks, 84% at 13 weeks, and 34% at 39 weeks. The screws had an initial (time zero) shear strength of 29.8+/-4.2 MPa, and maintained 97% of this strength at 26 weeks and 73% of this strength at 39 weeks. The inherent viscosity and molecular weight (M(w)) at time zero averaged approximately 1.4 dL/g and 165,000 g/mol, respectively, and decreased at similar rates for both the plates and screws. These results demonstrate excellent strength retention of devices fabricated from 70:30 poly(L-lactide-co-D,L-lactide) over time periods exceeding those associated with normal bone healing.

Absorbable Implants↗

PubMed2005

Viscoelastic material properties of the peripapillary sclera in normal and early-glaucoma monkey eyes.

PURPOSE: To test the hypothesis that changes in the viscoelastic material properties of peripapillary sclera are present within monkey eyes at the onset of early experimental glaucoma detected by confocal scanning laser tomography (CSLT). METHODS: Short-term (3-9 weeks), moderate (< or =44 mm Hg) intraocular pressure (IOP) elevation was induced in one eye of each of eight male monkeys by lasering the trabecular meshwork. This procedure generated early experimental glaucoma, defined as the onset of CSLT-detected optic nerve head (ONH) surface change, in the treated eye. Scleral tensile specimens from the superior and inferior quadrants of the eight early-glaucoma eyes were subjected to uniaxial stress relaxation and tensile tests to failure and the results compared with similar data obtained in a previous study of 12 normal (nonglaucomatous) eyes. Linear viscoelastic theory was used to characterize viscoelastic material property parameters for each specimen. Differences in each parameter due to quadrant and treatment were assessed by analysis of variance (ANOVA). RESULTS: Peripapillary sclera from the early-glaucoma eyes exhibited an equilibrium modulus (7.46 +/- 1.58 MPa) that was significantly greater than that measured in normal eyes (4.94 +/- 1.22 MPa; mean +/- 95% confidence interval, P < 0.01, ANOVA). Quadrant differences were not significant for the viscoelastic parameters within each treatment group. CONCLUSIONS: The long-term viscoelastic material properties of monkey peripapillary sclera are altered by exposure to moderate, short-term, chronic IOP elevations and these alterations are present at the onset of CSLT-detected glaucomatous damage to the ONH. Damage to and/or remodeling of the extracellular matrix of these tissues may underlie these changes in scleral material properties.

Animals↗

PubMed2004

MacroPore resorbable devices in craniofacial surgery.

Resorbable polymer implants have become a compelling option in the treatment of acquired and congenital craniofacial deformities. The resorbable polylactide (PLa) and polyglycolide (PGa) polymers in particular have demonstrated excellent safety profile sin multiple in vitro, animal, and clinical studies and are currently being used in a wide variety of craniofacial applications. In this article, the authors discuss the biomaterial properties of PLa and PGa resorbable implants and provide an overview of the use of these polymers in craniofacial surgery. They conclude by relating their experience with an ongoing clinical series using MacroPore PLDLa and FRP implants for various applications,including Le Fort osteotomies, midface/monobloc internal distraction, and craniosynostosis reconstruction.

Absorbable Implants↗

PubMed2004

Differential requirements for COPI transport during vertebrate early development.

The coatomer vesicular coat complex is essential for normal Golgi and secretory activities in eukaryotic cells. Through positional cloning of genes controlling zebrafish notochord development, we found that the sneezy, happy, and dopey loci encode the alpha, beta, and beta' subunits of the coatomer complex. Export from mutant endoplasmic reticulum is blocked, Golgi structure is disrupted, and mutant embryos eventually degenerate due to widespread apoptosis. The early embryonic phenotype, however, demonstrates that despite its "housekeeping" functions, coatomer activity is specifically and cell autonomously required for normal chordamesoderm differentiation, perinotochordal basement membrane formation, and melanophore pigmentation. Hence, differential requirements for coatomer activity among embryonic tissues lead to tissue-specific developmental defects. Moreover, we note that the mRNA encoding alpha coatomer is strikingly upregulated in notochord progenitors, and we present data suggesting that alpha coatomer transcription is tuned to activity- and cell type-specific secretory loads.

Animals↗

PubMed2003

A mechanical comparison and review of transverse, step-cut, and sigmoid osteotomies.

Successful incorporation of massive allografts for the treatment of bone deficiency demands maximizing biologic and mechanical factors. These factors have yet to be mastered, as evidenced by the 8% to 17% nonunion and the 5% to 20% fracture rate. The current study addresses the allograft incorporation process by examining the three construct geometries: transverse, step-cut, and sigmoid. Specimens were plated and mounted on a mechanical testing machine. A rotational displacement was applied, and torsional stiffness (N-m/ degrees ), maximum torque (N-m), and maximum displacement ( degrees ) were calculated. The sigmoid osteotomies had a torsional stiffness of 1.90 +/- 0.68 N-m/ degrees and maximum torque of 18.85 +/- 6.63 N-m versus 0.99 +/- N-m/ degrees and 14.48 +/- 2.15 N-m for the transverse osteotomies; and a maximum angular displacement of 11.60 degrees +/- 1.78 degrees versus 5.73 degrees +/- 1.6 degrees for the step-cut osteotomies. The step-cut osteotomies consistently failed at the step-cut corners, which acted as stress risers. Computer-aided solid modeling of the contact surfaces showed that the step and sigmoid osteotomy areas were 74% and 44%, respectively, larger than the transverse osteotomy. The sigmoid osteotomy, created with a template and pneumatic drill, seems to offer a mechanical advantage over the transverse and step-cut osteotomies by increasing stability and contact surface area relative to the transverse osteotomy but reducing the stress-riser effect of the step-cut osteotomy.

Biomechanical Phenomena↗

PubMed2003

The effect of divergent screw placement on the initial strength of plate-to-bone fixation.

BACKGROUND: Numerous implants exist that allow screws to be placed at varying angles for lag fixation or to fix additional fragments. This study determined how placing screws at different angles affects fixation strength. METHODS: Using a bone model, we first investigated the pullout strength of screws inserted at varying angles; then, we studied the strength of plate-bone constructs with end screws placed at divergent angles. RESULTS: Varying the screw angle from 0 to 10 to 20 degrees progressively weakened the screw pullout resistance. No additional decrease was found in varying the angle further. In contrast, the strength of fixation of plate to bone was higher for constructs with screws placed at 20 or 30 degrees off of perpendicular when tested in gap-open bending and axial compression (all p < 0.05). No such differences were found in torsion. CONCLUSION: The pullout strength with angled screws is reduced, but this does not translate into reduced strength of the bone-to-plate interface.

Analysis of Variance↗

PubMed2003

Viscoelastic characterization of peripapillary sclera: material properties by quadrant in rabbit and monkey eyes.

In this report we characterize the viscoelastic material properties of peripapillary sclera from the four quadrants surrounding the optic nerve head in both rabbit and monkey eyes. Scleral tensile specimens harvested from each quadrant were subjected to uniaxial stress relaxation and tensile ramp to failure tests. Linear viscoelastic theory, coupled with a spectral reduced relaxation function, was employed to characterize the viscoelastic properties of the tissues. We detected no differences in the stress-strain curves of specimens from the four quadrants surrounding the optic nerve head (ONH) below a strain of 4 percent in either the rabbit or monkey. While the peripapillary sclera from monkey eyes is significantly stiffer (both instantaneously and in equilibrium) and relaxes more slowly than that from rabbits, we detected no differences in the viscoelastic material properties (tested at strains of 0-1 percent) of sclera from the four quadrants surrounding the ONH within either species group.

Animals↗

PubMed2002

Modeling of the naked facet sign in the lumbar spine.

The study design is a computer visualization model that simulated flexion deformities about the lumbar spine for evaluation of the naked facet sign (NFS). The objectives were to ascertain the angles of rotation required for NFS to occur in the lumbar spine with various centers of rotation about the vertebral body and to assess whether NFS correlates with unstable flexion-distraction injuries in the lumbar spine. The presence of the NFS on axial computed tomography (CT) images occurs when the inferior articulating facet of the cephalad vertebra is not paired with an adjacent superior articulating facet of the caudal vertebra. This sign, when evidenced in the lumbar spine, is suggestive of significant injury secondary to a flexion-distraction force. A previous study using a computer-generated spine model challenged the utility of the NFS in the thoracolumbar spine. The NFS may prove to be more diagnostic of an unstable injury in the lumbar spine because of its normal lordotic resting position. A commercial spine computer visualization model was used to simulate various degrees of flexion injury in the lumbar spine. Lumbar functional spinal units (FSU) L2-L5 were each examined separately. The model simulated two CT scan slices (each 2 mm thick), which were created parallel to the inferior endplate of the cephalad vertebra of each FSU. The cephalad vertebra was rotated in 0.5 degrees increments until NFS was produced. The appearance of NFS required >/=11 degrees kyphotic angulation in more than two thirds of simulated centers of rotation about the lumbar vertebral bodies. The NFS was produced between a range of 8-24.5 degrees. For rotations about a point located 3 cm anterior to the vertebral body (to simulate seat-belt-type flexion-distraction injuries), the minimum angle required for NFS was 7.5 degrees. Our data correlate well with previously published results from in vitro and cadaveric studies. As opposed to the thoracolumbar spine, which normally rests in a neutral position, the lumbar spine normally rests in a lordotic position. Therefore, NFS in the lumbar spine may be more suggestive of an unstable injury and would warrant closer examination of the patient and additional radiographic studies.

Computer Simulation↗

PubMed2002

A caffeine diet can alter the mechanical properties of the bones of young ovariectomized rats.

The general public widely consumes caffeine which is contained in various foods, beverages, and over-the-counter medications. The relationships between caffeine intake and bone fractures is controversial. Therefore, the aim of the current study was to determine what effects, if any, caffeine intake in early life exerts on mechanical properties and mineral contents of bone in growing ovariectomized rats. A total of 8 dams with pups were divided into two groups. Group 1 was fed a 20% protein diet. Group 2 was fed a 20% protein diet supplemented with caffeine (4 mg/100 g). The respective diets were fed to the dams during lactation and to the pups continuously after weaning on day 22 until the end of the experimental period. On day 32, offspring from both groups were ovariectomized. On day 52, the rats were sacrificed and the femora removed. The biomechanical properties of the femora were determined by three-point bend testing to failure at a rate of 2 mm/min, with continuous data sampling at 10 samples/s. The properties determined included the modulus of elasticity, yield load, yield stress, ultimate load, ultimate stress, and the second moment of area. The caffeine group exhibited a decrease in the various mechanical properties (ranging from approximately 7 to 20%), except for yield strain and moment of inertia. The decreases in maximum stress and elastic modulus values were significant. Calcium, magnesium, and phosphorous values for the caffeine group were significantly decreased. These results suggest that the bone in the caffeine group is weaker and less stiff, with greater deformation under applied loading. It could be concluded that caffeine intake during the early growing period affects the mechanical properties of bone.

Animals↗

PubMed2002

Use of polylactide resorbable film as an adhesion barrier.

OBJECT: The present investigation evaluates two thicknesses of a resorbable polylactic acid (PLA) barrier film as an adhesion barrier to posterior spinal scar formation. METHODS: A readily contourable, thin film was placed directly over the dura. The thick film was placed above the lamina defect to act as a physical barrier inhibiting the prolapse of soft tissue into the epidural space. Through a combination of gross dissection with and without scar scores, quantitative analysis of collagen adjacent to the scar site, and histological evaluation, the resorbable adhesion barrier membranes were found to be effective treatment for reduction of posterior adhesions. CONCLUSIONS: The gross dissection demonstrated that both thicknesses of resorbable PLA barrier films created a controlled dissection plane, facilitated access to the epidural space, and provided a reduction in the tissue adherent to the dura.

Absorbable Implants↗

PubMed2002

Use of a resorbable sheet in iliac crest reconstruction in a sheep model.

OBJECT: Iliac crest bone graft harvesting can result in major complications, the rates of which range from approximately 6 to 8%. The objective of this study was to evaluate the postoperative regeneration of iliac crest donor defects in an animal model after harvesting a full-thickness tricortical graft. METHODS: In skeletally mature sheep, a tricortical iliac crest graft was harvested. The graft sites were allowed to heal unprotected or protected with the resorbable polylactic acid sheet material, MacroPore OS Protective Sheeting. After 6 months of healing, the sites were assessed by examination of undecalcified histological sections. Histomorphometric measurements of the original defect area, the area of new bone within the defect site, and the percentage of defect filled with new bone were quantified for both control and protected groups. In all histological sections, new bone growth within the defect sites appeared normal, with no observed excessive inflammatory cells. The developing bone tissue appeared to be remodeling normally. For the unprotected sites, the area of new bone averaged 16.3 mm2 (+/- 7.2 mm2), and the percentage of the defect area filled with bone averaged 10.7% (+/- 6.5%). In the protected sites, the area of new bone averaged 64.8 mm2 (+/- 11.6 mm2) and the percentage of the defect area filled with bone averaged 25.9% (+/- 1.6%). Both differences in area of new bone growth and percentage of defect area filled were statistically significant. Literature review has indicated that regeneration of donor site defects is desirable. CONCLUSIONS: Based on the results of the present study, MacroPore resorbable Protective Sheeting can improve bone regeneration significantly within the donor site following tricortical iliac crest graft harvesting.

Absorbable Implants↗

PubMed2002

Use of polylactide resorbable film as an adhesion barrier.

The present investigation evaluates two thicknesses of a resorbable polylactide barrier film as an adhesion barrier to posterior spine scar formation. A readily contourable, thin film was placed directly over the dura. The thick film was placed above the lamina defect to act as a physical barrier inhibiting the prolapse of soft tissue into the epidural space. Through a combination of gross dissection with and without scar scores, quantitative analysis of collagen adjacent to the scar site, and histologic evaluation, the resorbable adhesion barrier membranes were found to be effective treatment for reduction of posterior adhesions. The gross dissection demonstrated that both thicknesses of resorbable polymer barrier films created a controlled dissection plane, facilitated access to the epidural space, and provided a reduction in the tissue adhered to the dura.

Absorbable Implants↗

PubMed2002

Use of a resorbable sheet in iliac crest reconstruction in a sheep model.

Iliac crest bone graft harvesting can result in major complications that occur at rates of approximately 6%-8%. The objective of this study was to evaluate the postoperative regeneration of iliac crest donor defects in an animal model after harvesting a full-thickness tricortical graft. In skeletally mature sheep, a tricortical iliac crest graft was harvested. The graft sites were allowed to heal nonprotected or protected with the resorbable polylactic acid sheet material, MacroPore OS Protective Sheeting, (MacroPore Biosurgery, San Diego, Calif). After 6 months of healing, the sites were assessed by examination of undecalcified histologic sections. Histomorphometric measurements of the original defect area, the area of new bone within the defect site, and the percentage of defect filled with new bone were quantified for both control and protected groups. In all histologic sections, new bone growth within the defect sites appeared normal, with no excessive inflammatory cells observed. The developing bone tissue appeared to be remodeling normally. For the nonprotected sites, the area of new bone averaged 16.3 mm2 (+/-7.2 mm2), and the percentage of the defect area filled with bone averaged 10.7% (+/-6.5%). In the protected sites, the area of new bone averaged 64.8 mm2 (+/-11.6 mm2) and the percentage of the defect area filled with bone averaged 25.9% (+/-1.6%). Both differences in area of new bone growth and percentage of defect area filled were statistically significant. Literature review has indicated that regeneration of donor site defects is desirable. Based upon the results of the present study, MacroPore resorbable protective sheeting can improve bone regeneration significantly within the donor site following tricortical iliac crest graft harvesting.

Absorbable Implants↗