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Biomedical subjects

K J Baker

Publications and source records attributed to K J Baker.

15 recordsLinked to original sources

A biomechanical comparison of open and thoracoscopic anterior spinal release in a goat model.

STUDY DESIGN: A biomechanical assessment of anterior release and discectomy in the thoracic spine was performed on an animal model using thoracoscopic and open thoracotomy techniques. OBJECTIVES: To compare the relative efficacy of these two techniques of release in achieving increased spinal mobility. BACKGROUND DATA: The clinical use of video-assisted thoracoscopy in the correction of spinal deformity is increasing. The effectiveness of thoracoscopic anterior spinal release with discectomy has not been evaluated biomechanically. METHODS: Anterior release with discectomy was performed on six midthoracic motion segments in five mature goats. The thoracoscopic technique was used for three levels on one side, and an open thoracotomy was used for the alternating three levels of the contralateral side. The duration of surgery for disc excision and the amount of blood loss for each technique were recorded. The intact cranial and caudal motion segments served as controls. The motion segments were individually subjected to nondestructive biomechanical testing. Torsional, sagittal, and coronal bending torques were applied, and the resulting angular displacement was measured. RESULTS: The duration of surgery to remove a disc thoracoscopically decreased as experience was gained by the surgeon. The amount of intraoperative blood loss was comparable using the two methods. There was significantly increased flexibility in the released segments with both techniques, compared with the flexibility in the intact levels for all three loading directions. There was no difference in the motion obtained after release between the two techniques. CONCLUSION: Open and thoracoscopic anterior release and discectomy have been demonstrated, through biomechanical in vitro testing, to increase the flexibility of the spine to a similar extent.

Animals↗

Intraosseous infusion of prostaglandin E2 prevents disuse-induced bone loss in the tibia.

We investigated whether intraosseous injection of prostaglandin E2 would preserve tibial bone mass in the skeletally unloaded limb of a large animal model. Skeletal unloading of one rear limb was produced by unilateral Achilles tenectomy in the goat. Prostaglandin E2 was injected at 0.5 or 1.0 mg (1 ml of volume) twice daily, beginning on day 7 and continuing for 10 days, through an implant that had been surgically placed in the proximal tibial metaphysis. Thirty-five days after surgery, the tibiae were harvested for measurement of static and dynamic bone parameters and mechanical characteristics using transmission ultrasound. Prostaglandin E2 produced a dose-dependent increase in the formation of woven new bone at all bone envelopes. The 1.0 mg dosage prevented and partially reversed the effects of skeletal unloading and added new bone (p < 0.05) compared with the unloaded tibiae. Because prostaglandin E2 increased both bone formation and resorption and the new bone produced was primarily woven bone, the material properties of the tibiae infused with prostaglandin E2 did not increase significantly during the study compared with the unloaded and weight-bearing tibiae.

Animals↗

Effect of spinal construct stiffness on short segment fusion mass incorporation.

STUDY DESIGN: Three segment (L3-L5) pedicle screw constructs were implanted in caprine spines, and the resulting ankylosis evaluated mechanically and compared 12 weeks after surgery. OBJECTIVES: To determine if a construct of maximal stiffness could impair the biologic process of spinal arthrodesis by "stress-shielding." SUMMARY OF BACKGROUND DATA: Fusion mass stiffness is believed to be enhanced by increasing construct stiffness, although previous studies have used semirigid, nonconstrained constructs, which lose stiffness through cyclical loading. Device-related osteoporosis, reported to occur with stiff, constrained implants, may be more related to the presence of fusion induced by the implants rather than the implants themselves. METHODS: In 15 goats, L3-L5 segments were instrumented with pedicle screws, and four different diameters of rods (3.2 cm, 4.8 cm, 6.4 mm, and no rods) were implanted as longitudinal connections to vary the stiffness of the constructs. After 12 weeks, animals were killed and the segments were tested to determine their stiffness. RESULTS: In lateral bending, spines "fused" with rods (any size) were significantly stiffer (P = 0.03) than nonrodded spines. There was a trend toward stiffer segments with larger rods (4.8 cm or 6.4 mm) compared with 3.2 mm or no rods. There was a highly significant (P < 0.0001) increase in stiffness of all operated (rodded or nonrodded) segments compared with unoperated controls. CONCLUSIONS: The enhancement of segmental stiffness by stiffer constructs was confirmed, suggesting a beneficial effect on spinal arthrodesis by increasing stiffness. Stress shielding could not be shown.

Animals↗

Mechanism of inhibition of Ca(2+)-ATPase by myotoxin a.

The peptide DCRQKWKCCKKGSG [myotoxin-(29-42)], corresponding to residues 29-42 of myotoxin a, inhibits the activity of the Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum, with a Kd value of 19.4 microM at pH 7.5, in 100 mM KCl. The peptide YKQCHKKGGHCFPKEK, corresponding to residues 1-16 of myotoxin a, is a less potent inhibitor. Inhibition by myotoxin-(29-42) is reduced at low pH and at high ionic strength, suggesting that charge interactions are important in binding to the ATPase. Inhibition of the ATPase has been shown to follow from a decrease in the rate of dephosphorylation, with no effect on the rate of phosphorylation of the ATPase or on the rate of the Ca2+ transport step (E1PCa2-->E2P). Binding of myotoxin-(29-42) decreased the affinity of the ATPase for Ca2+ and Mg2+, and increased the rate of dissociation of the outer Ca2+ ion from the ATPase. Unlike the amphipathic peptide melittin, it is suggested that myotoxin-(29-42) does not bind significantly to the lipid bilayer portion of the sarcoplasmic reticulum. Fluorescence quenching studies suggest that it could bind to the ATPase in the vicinity of Cys-344 in the phosphorylation domain and Lys-515 in the nucleotide binding domain. Inhibition of the ATPase is observed when the ATPase is reconstituted in monomeric form in sealed vesicles, suggesting that aggregation of the ATPase is not involved in inhibition.

Amino Acid Sequence↗

Mechanism of inhibition of the Ca(2+)-ATPase by melittin.

The Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum is inhibited by melittin at pH 7.4. Melittin has no effect on the rate of phosphorylation of the ATPase or on the rate of the Ca2+ transport step, but melittin inhibits dephosphorylation of the phosphorylated ATPase at pH 7.3. At pH 6.0, melittin has no effect on ATPase activity or on the rate of dephosphorylation. At pH 7.4, inhibition of ATPase activity fitted to a Kd of 0.4 microM for melittin. Analogues of melittin in which the two Arg residues were replaced by Gln [melittin(RR to QQ)] or the two Lys residues were replaced by Gln [melittin-(KK to QQ)] also inhibited ATPase activity, but with an increased Kd value of 3.4 microM. Analogues of melittin containing an extra Lys residue at the C-terminus [melittin(+K)] or in which the Trp residue had been replaced with a Leu residue [melittin(W to L)] had the same effect on activity as melittin. Melittin and all the analogues increased the permeability of the SR membrane to Ca2+ with equal potency at pH 6.4, as shown by a reduction in level of Ca2+ accumulation. Melittin and all the analogues also shifted the E2-E1 equilibrium of the ATPase toward E1 with equal potency at pH 7.2, consistent with stronger binding to the E1 conformation. It is suggested that effects on Ca2+ permeability and on the E2-E1 equilibrium could follow from binding of the N-terminus of melittin at the membrane--water interface, and that effects on ATPase activity could follow from binding of the positively charged C-terminus between the phosphorylation and nucleotide binding domains.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Three-dimensional analysis of clubfoot deformity by computed tomography.

The bony pathoanatomy of clubfoot has been assessed by a three dimensional reconstruction of transverse CT images obtained from 27 feet in children aged 3-10 years. Principal axes of the bones were determined to quantitate interosseous deformity, while visual inspection of the reconstructed images demonstrated intraosseous deformity. "Medial spin" and midfoot adduction were analyzed on the AP view of the foot ("top" view), while hindfoot pronosupination was analyzed on the AP view of the ankle (posterior view). This technique allows visualization of deformities which normally cannot be analyzed on plain radiographs, and also shows that a variety of interosseous relationships make up the clinical entity known as clubfoot. Abnormal talar pronation ("intorsion") was an unexpected finding of this three dimensional analysis.

Child↗

Localization of the hinge region of the Ca(2+)-ATPase of sarcoplasmic reticulum using resonance energy transfer.

The Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum can be labelled at Cys-670 and Cys-674 with 5-[[2-[(iodoacetyl) amino]ethyl]amino]naphthalene-1-sulphonic acid (IAEDANS). Resonance energy transfer has been used to measure the distance between Cys-670/Cys-674 and Glu-439 labelled with 5-(bromomethyl)fluorescein as 40 A. The height of Cys-670/Cys-674 above the phospholipid/water interface has been measured by resonance energy transfer between IAEDANS-labelled ATPase and fluorescein-labelled phosphatidylethanolamine as 54 A. This locates the hinge region of the ATPase close to the mouth of the pore observed in the cytoplasmic region of the ATPase in electron micrographs. No significant changes in these distances can be detected by resonance energy transfer on binding Ca2+ or vanadate. The height of the IAEDANS label above the phospholipid/water interface is the same for bilayers of dimyristoleoylphosphatidylcholine and dioleoylphosphatidylcholine. Conformation changes on the Ca(2+)-ATPase appear to be localised to small regions of the ATPase.

Binding Sites↗

Mechanical consequences of core drilling and bone-grafting on osteonecrosis of the femoral head.

We employed an anatomically realistic three-dimensional finite-element model to explore several biomechanical variables involved in coring or bone-grafting of a segmentally necrotic femoral head. The mechanical efficacy of several variants of these procedures was indexed in terms of their alteration of the stress:strength ratio in at-risk necrotic cancellous bone. For coring alone, the associated structural compromise was generally modest, provided that the tract did not extend near the subchondral plate. Cortical bone-grafting was potentially of great structural benefit for femoral heads in which the graft penetrated deeply into the superocentral or lateral aspect of the lesion, ideally with abutment against the subchondral plate. By contrast, central or lateral grafts that stopped well short of the subchondral plate were contraindicated biomechanically because they caused marked elevations in stress on the necrotic cancellous bone. Calculated levels of stress were relatively insensitive to variations in the diameter of the graft.

Bone Transplantation↗

Structural consequences of subchondral bone involvement in segmental osteonecrosis of the femoral head.

Appearance of a crescent sign usually marks the onset of necrotic femoral head collapse, but very little is known about which local factors contribute most critically to avoiding or postponing fracture of at-risk juxtaarticular cancellous bone. A three-dimensional finite element model was used to test the hypothesis that an initially mechanically uncompromised subchondral plate could provide a substantial degree of stress protection to a weakened underlying segmental infarction. The computational simulation of osteonecrosis showed that the principal stress distribution for an assumption of subchondral plate weakening (given also an underlying, comparably weakened segmental infarction) differed inappreciably from that of a normal femoral head. However, the tendency for local structural failure, as reflected in the ratio of stress to strength, was substantially higher in the former instance. If, instead, the mechanical integrity of the subchondral plate overlying the weakened segmental infarction was assumed to be preserved, computed stress levels in the at-risk subjacent necrotic cancellous bone were still over 70% as high as for the weakened-plate case. The data thus indicate that even a fully normal subchondral plate can provide only modest stress protection of a weakened underlying segmental infarction, whereas weakening of the necrotic cancellous bone throughout the infarction induces marked stress increase in the overlying subchondral plate. These findings suggest that the onset of collapse is probably dominated much more strongly by the degree of structural degradation of the cancellous bone within the main infarct body, than by the degree of structural degradation within the subchondral plate.

Computer Simulation↗

A finite-element analysis of the effects of intertrochanteric osteotomy on stresses in femoral head osteonecrosis.

The efficacy of osteotomy for the precollapse stage of femoral head necrosis depends on altering load transmission. The alteration must reduce the stress levels on the infarcted bone during the process of repair. The prospects for success in this regard would likely be improved by the ability to predict reliably the stress changes derived from specific osteotomies for specific femoral head involvement patterns. For this reason, an anatomic three-dimensional finite-element model has been designed to compute necrotic femoral head stress changes that accompany varus, valgus, and rotational osteotomies. Four specific patterns of femoral head infarction are considered. Comparison of the patterns of load transmission at ten discrete instants (spanning the stance phase of the gait cycle) revealed that the critical stresses in the most commonly infarcted anterolateral and central femoral head regions occur just after the instant of heel-strike. For the femoral head with a deep, narrow lesion in the weight-bearing tract, and for classic wedge-shaped segmental infarct, the data showed that 30 degrees varus osteotomy was beneficial in reducing stress levels through much of the infarcted region. The 30 degrees valgus osteotomy was less successful. Neither 30 degrees anteversion nor 30 degrees retroversion osteotomies caused substantial changes in stresses for infarcted regions along the weight-bearing tract. For the case of a wide, shallow lesion or for whole femoral head involvement, none of the four osteotomies considered was able to achieve appreciable net reduction of stresses in weakened, infarcted regions.

Adult↗

Defective regulation of vasopressin gene expression in Brattleboro rats.

The Brattleboro rat has severe diabetes insipidus due to an autosomal recessive trait resulting in the inability to synthesize detectable amounts of hypothalamic vasopressin. To determine whether this abnormality is due to a regulatory defect in the Brattleboro rat's vasopressin gene, we studied changes in the hypothalamic content of vasopressin mRNA in normal Long-Evans and homozygous Brattleboro rats subjected to osmotic stress and correlated these changes with systemic responses to water deprivation. We report that the Brattleboro rat does have a marked defect in the regulation of vasopressin gene expression consisting of an inability to increase hypothalamic vasopressin mRNA content in response to severe osmotic stress.

Animals↗

Hydrocortisone choleresis in the dog.

Hydrocortisone sodium succinate (Solu-Cortef; Upjohn Co., Kalamazoo, Mich.) has been found to induce choleresis in unanesthetized fasting dogs fitted with Thomas duodenal cannulae for direct quantitative collection of bile. In all experiments, bile flow increased (average, 68%) 15-20 min after beginning hydrocortisone by infusion in association with an equivalent increment in the output of sodium, potassium, chloride, and bicarbonate. In five animals, the choleretic response occurred independently of, and apparently additive to, the effect of simultaneously administered sodium taurocholate. The fluid added to the bile resembled an ultrafiltrate of plasma. Erythritol clearance increased in proportion to flow, suggesting an effect at the hepatocellular rather than ductal level and probably independent, therefore, of endogenous secretin release. Hydrocortisone and its metabolites were excreted in amounts too small to induce choleresis osmotically. Simultaneous administration of sulfobromophthalein sodium blocked the choleretic response without preventing hydrocortisone excretion. The data suggest that a previously ill-defined mechanism of canalicular bile formation, not mediated by bile salt excretion, may be operative in choleretic response to a variety of agents.

Animals↗

Three-dimensional computer analysis of complex acetabular insufficiency.

Fourteen patients with acetabular dysplasia were studied by using three-dimensional computed tomography (CT) reconstructions before pelvic osteotomies. Computer manipulation of the data allowed a preoperative visual assessment of acetabular shape, assessment of potential congruency between the femoral head and acetabulum by using a mathematical best-fit sphere, and measurement of surface contact distances that depict joint coverage and relate to concentration of weight-bearing forces. Preoperative evaluation of the three-dimensional images for these 14 patients allowed improved understanding of their abnormal anatomy and better surgical planning.

Acetabulum↗