Biomedical subjects

R B Martin

Publications and source records attributed to R B Martin.

At least 55 records · Page 3Linked to original sources

PubMed1996

Osteonal structure in the equine third metacarpus.

In studying the flexural fatigue properties of the equine third metacarpal (cannon) bone, we previously found that the dorsal region was weaker monotonically, but more fatigue resistant, than the lateral region. Fatigue resistance was associated with fracture surfaces which demonstrated that secondary osteons had "pulled out" of the surrounding matrix; this never happened in lateral specimens. We therefore became interested in the osteonal structure of this bone, and began to study its birefringence patterns in circularly polarized light. We found that the predominant type of secondary osteon was one in which only the outermost few lamellae were circumferential, with the inner lamellae being longitudinally oriented. This "hoop" pattern had not been described in Ascenzi's classic papers. Using basic fuchsin-stained, undecalcified cross-sections from the dorsal, medial, and lateral midshaft regions of 12 pairs of cannon bones, we classified 360 secondary osteons according to their birefringence patterns, and measured their inner and outer diameters. We found that variants of the hoop category comprised 60% of all osteons, but were significantly less common in the dorsal region, where the predominant types were Ascenzi's "longitudinal" or "alternating" patterns. The dorsal region also had smaller osteons (OD = 156 +/- 19 microns) than the medial (179 +/- 13 microns, p = 0.0004) and lateral (182 +/- 13 microns, p = 0.0001) regions. We postulate that these regional variations in osteonal size and structure, which are obviously produced by regional variations in remodeling, have important mechanical implications.

Analysis of Variance↗

PubMed1996

Collagen fiber organization is related to mechanical properties and remodeling in equine bone. A comparison of two methods.

We studied birefringence as an indicator of collagen fiber orientation in the diaphysis of the equine third metacarpal bone. We had previously shown that tissue from the lateral cortex of this bone is stronger monotonically, but less fatigue resistant, than tissue from the medial and dorsal regions. To learn whether collagen fiber orientation might play a role in this regional specialization, we tested three hypotheses using the same specimens: (1) collagen fiber orientation is regionally dependent; (2) remodeling changes collagen fiber orientation; (3) longitudinal collagen fibers correlate positively with modulus and monotonic bending strength and negatively with flexural fatigue life. Beams (N = 36) cut parallel to the long axes of six pairs of bones had been tested to determine elastic modulus (N = 36), and fatigue life (N= 24) or monotonic strength (N = 12) in four-point bending. Subsequently, histologic cross-sections were prepared, and porosity, active remodeling and past remodeling were quantified. Birefringence was measured as an indicator of transverse collagen orientation using plane-polarized light (PPL), and again using circularly polarized light (CPL). The CPL measurement was less variable than the PPL measurement. Both birefringence measures indicated that collagen was more longitudinally oriented in the lateral cortex than in the other two cortices. Longitudinally disposed collagen correlated with greater modulus and monotonic strength, but did not correlate with fatigue life. Remodeling was associated with more transverse collagen. Neither measure of birefringence was significantly correlated with porosity. It was concluded that, in the equine cannon bone, longitudinal collage fiber orientation is regionally variable, contributes to increased modulus and strength but not fatigue life, and is reduced by osteonal remodeling.

Animals↗

PubMed1995

Fatigue behavior of the equine third metacarpus: mechanical property analysis.

This is the first in a series of experiments to study the fatigue properties of equine cannon (third metacarpal) bone specimens from Thoroughbred racehorses. Monotonic and fatigue tests to failure were performed in four-point bending on diaphyseal specimens in a 37 degrees C saline bath to answer three initial questions. (a) Will a linear variable differential transducer yield the same elastic modulus as strain gauges? (b) Will fatigue results depend on whether the periosteal or endosteal side of the beam is in tension? (c) Are there regional variations in the monotonic and fatigue properties of the cannon bone midshaft? Eighteen left-right pairs of specimens from six horses were used. One beam of each pair was fitted with strain gauges. Fatigue tests were conducted on 24 specimens under load control at 2 Hz; an initial range of 0-10,000 microstrain was used so as to produce failure in a reasonable period of time. There were no left-right differences in the fatigue or monotonic properties, and the presence of a gauge had no effect on modulus measured by a linear variable differential transducer. However, gauge-measured moduli were about 1 GPa less than transducer-measured values. Fatigue life was independent of which side of the beam was in tension, and there were significant variations in mechanical properties around the cortex. The lateral region was stiffer than the dorsal region but the latter had a longer fatigue life. The fixed cylindrical supports used in this experiment eventually produced slight wear grooves, causing artifactual stiffening at the end of the load cycle in some specimens. A second experiment using roller supports confirmed the reason for this stiffening. It also showed that fatigue life was shorter when roller supports were used but regional differences were similar.

Analysis of Variance↗

PubMed1994

Involvement and role playing.

Three studies focused on involvement as a function of type and content of the role play, experimenter behaviors, and proportion of time in scenario roles. Several measures of involvement were obtained. Generally, there was a low correlation between involvement estimated by observers and self-reported involvement; subjective involvement also was related more consistently to other variables.

Adult↗

PubMed1994

The relationship between mass and acceleration for impacts on padded surfaces.

It is shown analytically that when an object impacts a deformable surface, the acceleration it experiences is inversely proportional to its mass. This is because acceleration is reduced by deformation of the surface, and more massive objects deform the surface more. Since head injury is thought to depend more on acceleration than applied force, this result implies that children may be at greater risk than adults when striking a padded surface. To test the theoretical prediction, 2.69 and 7.40 kg missiles were dropped 31.8 cm onto three deformable surfaces: dry sod, moist sod, and an artificial playing surface. Impact force was measured with a force plate, and divided by missile mass to obtain acceleration. For each test surface, the smaller mass produced a larger acceleration than the larger mass, confirming the theoretical result. Additionally, load-deformation characteristics of the three surfaces were measured, and the results used to predict the effects of mass on acceleration during impact. The predicted results agreed well with the experimental data for the artificial surface (2.3% difference) and moist sod (5.7% difference), but less well for dry sod (21% difference).

Acceleration↗

PubMed1994

Citrate as the main small molecule binding Al3+ in serum.

A recent proposal (Clin Chem 1992;38:1809-18) that inorganic phosphate is the predominant small molecule binding Al3+ in blood serum is shown to be incorrect. Experiments in which Al3+ is added to solutions containing phosphate and citrate in the same proportions as in serum clearly show that citrate prevents formation of any aluminum phosphate precipitate, and analysis of these data indicates that the assumed binding constants for soluble phosphate are two orders of magnitude too strong. Consideration of the effect of competitive binding of alkaline earth metal ions to citrate on Al3+ binding and of a set of transferrin-Al3+ stability constants leads to the conclusion that the proportions are in close agreement with previously published results. We conclude on the basis of stability constants that, of the Al3+ in blood serum, approximately 89% (+/- 5%) binds to transferrin and approximately 11% (+/- 5%) to citrate.

Aluminum↗

PubMed1993

Changes in bone in a model of spinal cord injury.

Bone calcium, histomorphometry, and mechanical strength were evaluated in a model of spinal cord injury. Cortical bone area and rates of formation and apposition at the tibiofibular junction (TFJ) and midshaft of the humerus were measured at 35-42, 42-77, and 77-94 days after transection of the spinal cord. All comparisons were between the animals with a spinal lesion and control animals. A 0.34% difference in the length of the tibia of the two groups of animals was observed, the dry weight of the tibia was 28.4% less in rats with a lesion, and there was no significant difference in the amount of calcium per milligram of bone. At 35 days after surgery, the cortical area in the midshaft of the humerus was slightly less (11%) in rats with a lesion, but by 94 days there was no difference in cortical or medullary area. The final (day 94) cortical area at the TFJ in rats with a lesion was less than that in the controls. Bone formation at the TFJ was similar in both groups in the period of 35-42 days and was similar at 77-94 days in the animals with a lesion, and rates of formation and apposition were greater in the humerus of rats with a lesion; the rates did not differ significantly between groups at either site. At 94 days, trabecular bone area in the tibial metaphysis was 41% less in rats with a lesion. Mechanical parameters were significantly less in the femora, but not the humeri, of rats with a lesion.

Animals↗

PubMed1993

Bone ingrowth and mechanical properties of coralline hydroxyapatite 1 yr after implantation.

A previous study of coralline hydroxyapatite as a bone-graft substitute was extended from 4 to 12 months to determine better the relationships between implantation time, bone ingrowth and mechanical properties. The model consisted of a 10 x 30 mm window defect in the shaft of the canine radius (a cortical site), and a 10 mm diameter cylindrical defect in the head of the humerus (a cancellous site). In the new study, these two defects were made bilaterally in eight dogs, and filled with block-form coralline hydroxyapatite. The radius defects were supported by a metal fixation plate which was removed after 9 months. After 12 months, the dogs were killed and the left-side implants were analyzed histomorphometrically and mechanically. The right-side radius and humerus were reserved for structural analysis. The results were combined with those previously measured after 4, 8, 12 and 16 wk of implantation. In the cortical site, bone ingrowth increased from 52% at 16 wk to 74% at 1 yr. In the cancellous site, bone ingrowth was 38% after 4 wk, then fell monotonically, reaching 17% at 1 yr. Bending and compressive strength and stiffness of the radius implants increased throughout the post-implantation year, but compressive strength and stiffness of the humerus implants did not change after the first 2-4 months. Mechanical properties were strongly correlated to bone ingrowth in the cortical, but not the cancellous, site. The volume fraction of the coralline hydroxyapatite material diminished significantly with time in the cortical, but not the cancellous, site.

Animals↗

PubMed1993

The effects of collagen fiber orientation, porosity, density, and mineralization on bovine cortical bone bending properties.

The relationship between the mechanical properties of bone in three-point bending and eight histocompositional variables was studied. Ultimate stress, ultimate strain, and elastic modulus were measured in 35 beams of cortical bone from bovine tibias using standard ASTM methods. Four elements of porosity were determined by point counting, mineralization by ashing, and wet and dry apparent density from weight and volume. Collagen fiber orientation was estimated using polarized light, and specimens were categorized as plexiform, mixed, or osteonal. Analysis of variance showed that ultimate stress was similar in the plexiform and osteonal specimens, but elastic modulus was reduced in the latter (18.6 +/- 1.2 vs 21.0 +/- 1.9 GPa), which were significantly less porous (by 24%) and less mineralized (by 3%) than the plexiform group. Stepwise multiple regression analysis showed that collagen fiber orientation ranked highly as a predictor of bending properties. The next best predictors were density and mineralization. In the plexiform group, 77% of the variability in elastic modulus was accounted for by wet and dry density and collagen fiber orientation. In the osteonal group, 88% of modulus variability was accounted for by percentage mineralization and collagen fiber orientation. When all the specimens were pooled, 62% of the variability in elastic modulus was attributable to variations in collagen fiber orientation, density, and porosity due to Haversian canals.

Animals↗

PubMed1993

Emotional crying, depressed mood, and secretory immunoglobulin A.

The relationship between emotional crying and secretory immunoglobulin A (S-IgA) in whole saliva was examined. Previous research had indicated that lower S-IgA was associated with crying. Similar results were found in the present study. Depressed mood was not associated with S-IgA.

Adult↗

PubMed1992

Cooperative proton and calcium binding by sarcoplasmic reticulum ATPase.

The classic work on binding of calcium to CaATPase is analyzed by an objective non-linear least squares procedure of 74 data points over six pH values. Binding of two calciums to the basic form of the sites occurs with an equilibrium stability constant product of log K1K2 = 13.2. Owing to competition from protons, this value drops in acidic and neutral solutions, becoming, for example, 11.9 at pH 6.8. Binding of the two calciums is so strongly cooperative that its extent is difficult to estimate reliably; there is very little of the one calcium species. Two protons are also bound cooperatively to the calcium sites. In solutions of calcium free protein, at pH less than 7.6 the predominant species holds two protons at the calcium sites, while at greater pH the dominant species bears no protons; there is very little of the intermediate one proton species. The analysis also reveals the likely presence of a small, less than statistical, amount of a ternary complex bearing one calcium and one proton.

Adenosine Triphosphatases↗

PubMed1992

Aluminium speciation in biology.

Before we can understand the role of Al3+ in living organisms we need to learn how it interacts with molecules found in biological systems. The only aluminium oxidation state in biology is 3+. In aqueous solutions there are only two main Al(III) species: the hexahydrate Al3+ at pH < 5.5 and the tetrahedral aluminate at pH > 6.2. In the blood plasma, citrate is the main small molecule carrier and transferrin the main protein carrier of Al3+. In fluids where the concentrations of these two ligands are low, nucleoside di- and triphosphates become Al3+ binders. Under these conditions Al3+ easily displaces Mg2+ from nucleotides. When all three classes of ligands are at low concentrations, catecholamines become likely Al3+ binders. Double-helical DNA binds Al3+ weakly and under no conditions should it compete with other ligands. Al(III) in the cell nucleus probably binds to nucleotides or phosphorylated proteins. Al3+ undergoes ligand exchange much more slowly than most metal ions: 10(5) times slower than Mg2+.

Aluminum↗

PubMed1992

Optimal control of tumor size used to maximize survival time when cells are resistant to chemotherapy.

The high failure rates encountered in the chemotherapy of some cancers suggest that drug resistance is a common phenomenon. In the current study, the tumor burden during therapy is used to slow the growth of the drug-resistant cells, thereby maximizing the survival time of the host. Three types of tumor growth model are investigated--Gompertz, logistic, and exponential. For each model, feedback controls are constructed that specify the optimal tumor mass as a function of the size of the resistant subpopulation. For exponential and logistic tumor growth, the tumor burden during therapy is shown to have little impact upon survival time. When the tumor is in Gompertz growth, therapies maintaining a large tumor burden double and sometimes triple the survival time under aggressive therapies. Aggressive therapies aim for a rapid reduction in the sensitive cell subpopulation. These conclusions are not dependent upon the values of the model constants that determine the mass of resistant cells. Since treatments maintaining a high tumor burden are optimal for Gompertz tumor growth and close to optimal for exponential and logistic tumor growth, it may no longer be necessary to know the growth characteristics of a tumor to schedule anticancer drugs.

Animals↗

PubMed1992

Low-intensity combination chemotherapy maximizes host survival time for tumors containing drug-resistant cells.

Recent clinical trials have shown that for some cancers, high-intensity alternating chemotherapy does not significantly improve either survival times or response rates compared with nonalternating therapy. The current study uses optimal control to determine the best way to treat a tumor that contains drug-resistant cells that cannot be destroyed. The delivery of two non-cross-resistant chemotherapeutic agents is limited by bounds on the drug concentration and the dose intensity. This ensures that the drug toxicity stays within a tolerable range. The aim of the therapy is to maximize the host survival time, defined as the time over which the tumor burden can be kept below a fixed bound. The model is posed as a free terminal time, optimal parameter selection problem in which the constraints are continuously parametrized by time and the number of courses of therapy is free to vary. New theory is developed so that the optimal parameter selection problem can be solved as a sequence of fixed terminal time problems using existing optimal control software. Numerical simulations of Gompertz tumor growth showed that a treatment maintaining a high tumor burden doubled and sometimes tripled with survival time under aggressive therapy. When these simulations were repeated using exponential and logistic tumor growth models, the tumor burden during treatment had little influence upon survival time. In all simulations, survival time was not extended by delivering the anticancer drugs concurrently instead of staggering the treatment arms.

Animals↗

PubMed1992

A worst-case optimal parameter selection model of cancer chemotherapy.

An optimal parameter selection model of cancer chemotherapy in which two system parameters are unknown is formulated as a worst-case optimal parameter selection model. The model assumes that the unknown parameters lie within a known set. The system constraints must be satisfied over this entire set, and the objective function minimized in the worst case. The continuous dependence of the objective function and the system constraints upon the unknown parameters can be removed, making a numerical solution tractable. For the data considered it is proven that a cure is impossible no matter what the values of the unknown parameters in the parameter set. The optimal policy is shown to be relatively low dose intensity for the majority of the treatment, with the remaining drug delivered towards the end of the treatment interval.

Humans↗

PubMed1992

Histological features of the dorsal cortex of the third metacarpal bone mid-diaphysis during postnatal growth in thoroughbred horses.

The dorsal cortex of the equine third metacarpal mid-diaphyseal bone was characterised during growth by the histological and microradiographic examination of specimens from 30 horses ranging in age from 2 months to 8 y. Bone from horses aged less than 6 months was characterised by rapid periosteal apposition of circumferential trabeculae of woven bone that were next connected by radial trabeculae to the parent cortex. Deposition of lamellar bone on the inner trabecular surfaces resulted in rows of primary osteons. Replacement of primary bone occurred only after 4 months of age and preferentially in the woven interstitial bone separating rows of primary osteons formed in the postnatal periosteal cortex. Resorption cavities and incompletely filled secondary osteons characterised bone of 1 and 2-y-old horses. Bone from horses older than 3 y contained several generations of secondary osteons, fewer resorption spaces and incompletely filled osteons, and had a greater portion of circumferentially oriented collagen fibres than bone from younger horses. Bone from horses older than 5 y had large resorption cavities characterised by irregular boundaries. We propose that the process of periosteal bone tissue apposition observed in growing foals be called 'saltatory primary osteonal bone formation' and that this process results in faster cortical expansion and larger total surface area for bone deposition than circumferential lamellar, simple primary osteonal, and plexiform mechanisms of periosteal bone formation. We speculate that bone from 1 and 2-y-old horses would be more susceptible to fatigue microdamage resulting from compressive loads because of high porosity, few completed secondary osteons and low proportion of circumferentially oriented collagen fibres.

Aging↗

PubMed1991

The assessment of involvement in role playing.

Two experiments (N = 169) focused on involvement in role playing. Subjects rated their level of involvement after each enactment; in addition, a probe procedure was used with prompts, increasingly disparate from the content of the role play. In the first experiment, subjects role played an anger of sad scenario; both measures of involvement correlated with emotional response, but were not correlated with each other. In the second experiment, involvement was manipulated experimentally; both measures varied as expected with the manipulation.

Adult↗

PubMed1991

Determinants of the mechanical properties of bones.

The mechanical properties of bones are governed by the same principles as those of man-made load-bearing structures, but the organism is able to adapt its bone structure to changes in skeletal loading. In this overview of the determinants of the strength and stiffness of bone, a continuum approach has been taken, in which the behavior of a macroscopic structure depends on its shape and size, and on the mechanical properties of the material within. The latter are assumed to depend on the composition (porosity and mineralization) and organization (trabecular or cortical bone architecture, collagen fiber orientation, fatigue damage) of the bone. The effects of each of these factors are reviewed. Also, the possible means of non-invasively estimating the strength or other mechanical properties of a bone are reviewed, including quantitative computed tomography, photon absorptiometry, and ultrasonic measurements. The best estimates of strength have been obtained with photon absorptiometry and computed tomography, which at best are capable of accounting for 90% of the strength variability in a simple in vitro test, but results from different laboratories have been highly variable.

Animals↗