T. Aidan Cockburn, 1912--1981: a memorial

This study explores age-related thinning of cortical bone in an area of the femur that is becoming of increasing clinical interest. It is based on measurements of medial-lateral and posterior-anterior radiographs of the proximal one-third of the right femur, below the greater trochanter. The study population consisted of 458 skeletons from the Terry collection and included approximately equal numbers of blacks and whites, males and females, aged 20 to 98 years. Cortical thicknesses were measured at 11 levels, beginning with a line drawn perpendicular to the linea aspera at the level of the inferior border of the greater trochanter. The four quadrants (medial, lateral, anterior, posterior) differed in amount of change with age. In general, except for the relatively thick medial cortex, intertrochanteric levels showed less change than subtrochanteric levels. It is postulated that this is because the greatest remodeling activity takes place in trabecular rather than cortical bone in the intertrochanteric region. The anterior and posterior cortex showed the most regular and greatest amount of thinning with age. In males at lower levels, there was little or no loss in either medial or lateral cortex, but females showed considerable loss after the sixth decade. It is suggested that a stress-related “maintenance” factor retards cortical thinning in these quadrants. A review of the literature suggests that age-related cortical loss in the femur may have been accelerated in archaeological population, compared with modern groups.     

Skeletal Manifestations of Hydatid Disease in Serbia: Demographic Distribution,Site Involvement,Radiological Findings,and Complications

Although Serbia is recognized as an endemic country for echinococcosis, no information about precise incidence in humans has been available. The aim of this study was to investigate the skeletal manifestations of hydatid disease in Serbia. This retrospective study was conducted by reviewing the medical database of Institute for Pathology (Faculty of Medicine in Belgrade), a reference institution for bone pathology in Serbia. We reported a total of 41 patients with bone cystic echinococcosis (CE) during the study period. The mean age of 41 patients was 40.9±18.8 years. In 39% of patients, the fracture line was the only visible radiological sign, followed by cyst and tumefaction. The spine was the most commonly involved skeletal site (55.8%), followed by the femur (18.6%), pelvis (13.9%), humerus (7.0%), rib (2.3%), and tibia (2.3%). Pain was the symptom in 41.5% of patients, while some patients demonstrated complications such as paraplegia (22.0%), pathologic fracture (48.8%), and scoliosis (9.8%). The pathological fracture most frequently affected the spine (75.0%) followed by the femur (20.0%) and tibia (5.0%). However, 19.5% of patients didn''t develop any complication or symptom. In this study, we showed that bone CE is not uncommon in Serbian population. As reported in the literature, therapy of bone CE is controversial and its results are poor. In order to improve the therapy outcome, early diagnosis, before symptoms and complications occur, can be contributive.     

Anatomical differences in the femur and tibia between Negroids and Caucasoids antheir effects upon locomotion.

Nine variables of length, width and circumference of the femur and tibia were measured on post-cranial remains of 28 Caucasoids and 45 Negroids. The distance from the point of tibial attachment of the patellar ligament to the head of the tibia (PLID) was also determined. It was found that the Negroid has a significantly longer and narrower femur and tibia than the Caucasoid, although PLID did not vary between the two groups. Thus PLID, relative to the length of the tibia, was less in Negroids than Caucasoids. A factor analysis was carried out in order to examine the relation between PLID and the other variables. It appeared that the same three factors governed the ten variables in both races. In Caucasoids, PLID did not load on either the "length" or "width" factors and appeared unique. In Negroids, PLID loaded on Factor III with two width measures, and this factor correlated positively with the "width" factor. It is suggested that in Caucasoids PLID does not relate to length or width dimensions of the leg but in Negroids it is related to width rather than length.     

Pharmacokinetics of an antiangiogenic ribozyme (ANGIOZYME) in the mouse.

Vascular endothelial growth factor (VEGF) is a growth factor that contributes to the angiogenesis of developing tumors. To interfere with the action of VEGF, a nuclease-stabilized ribozyme, ANGIOZYME, has been developed against VEGF receptor subtype Flt-1 mRNA. To determine which routes of administration would be useful for systemic delivery of this ribozyme, a dose of 30 mg/kg [32P]ANGIOZYME was administered as an i.v., i.p., or s.c. bolus. Concentrations of ANGIOZYME in plasma, femur, kidney, liver, and lung were examined. ANGIOZYME was well absorbed after i.p. (90%) or s.c. administration (77%), with peak plasma concentrations occurring 30 minutes after dosing. Total body clearance after a single dose of 30 mg/kg ANGIOZYME was 20 ml/min/kg, and the elimination half-life was 33 minutes. The apparent volume of distribution at steady-state ranged from 0.5 to 1.3 L/kg. ANGIOZYME was detected in the four tissues examined through the 3 hour sampling period after i.v. or i.p. administration. After s.c. administration, ANGIOZYME was detected in femur, kidney, and lung but not in the liver. The highest concentrations of ANGIOZYME were found in kidney and femur with all three routes. Because of the rapid and extensive absorption after extravascular injections, either i.p. or s.c. administration could be considered for use in pharmacodynamic studies examining the effects of ANGIOZYME or other ribozymes with similar chemical modifications.     

Femur/stature ratio and estimates of stature in children.

The present study examines the relationship between femur length and stature in children between the ages of 8 and 18 years. In previous investigations, my colleagues and I reported the surprising finding that femur length bears a nearly constant relationship to stature in adult humans regardless of ethnicity or gender. This earlier study revealed that the femur/stature ratio averages 26.74% in adult humans, and that using the ratio to predict stature from femur length yields remarkably accurate estimates. The current study shows that femur/stature ratios of children between the ages of 8 and 11 differ significantly from their older counterparts. Between the ages of 12 and 18, there are no significant differences due to age in the femur/stature ratio; however, there are significant differences in this age group attributable to gender. This study also shows that the worldwide average adult femur/stature ratio does not adequately describe children in this age range. This study strongly documents the adolescent growth spurt in the femur/stature ratios of both males and females at the precise time one would expect to see the spurt occur (10-12 in females; 12-14 in males). This growth follows a nearly identical trajectory in both genders, with relative femur growth dominating before the peak years of the growth spurt, and relative stature growth dominating afterward. This accounts for the ratio's rise to maximum values just before peak growth, and its decline toward the adult ratio thereafter. These findings require us to use separate adolescent femur/stature ratios of 27.16 (females) and 27.44 (males) to estimate the stature of children between the ages of 12 and 18. Preliminary testing shows these ratios to be more accurate in estimating stature than the properly selected Trotter and Gleser adult regression equation. Use of the adolescent male ratio with the Homo erectus juvenile WT 15000 results in a lower stature estimate (157.4 cm) than previously reported. It is suggested that continued testing of the ratio occur, but that the values herein derived may be useful in routine forensic cases involving children in this age range, and with subadult paleontological specimens.     

Albino corpus cardiacum extracts induce morphometric gregarization in isolated albino locusts, Locusta migratoria, that are deficient in corazonin

Abstract.  The neuropeptide [His⁷]-corazonin, present in the central nervous system and corpus cardiacum, is known to mimic a 'gregarizing' effect on phase-related morphometric ratios (hind femur length/maximum head width and fore wing length/hind femur length) when injected into locusts reared in isolation. However, an albino strain is known to exhibit phase-specific changes in these ratios in response to rearing density, although it is deficient in [His⁷]-corazonin. To examine whether there is a second factor responsible for this phenomenon, perhaps a corazonin-like factor that has lost its dark-colour inducing activity, methanol extracts of corpora cardiaca taken from crowd-reared albino nymphs of Locusta migratoria are injected into isolated-reared second-stadium albino nymphs and reared to adults in isolation. The hind femur length/maximum head width and fore wing length/hind femur length ratios are significantly different from those of control oil-injected counterparts, and shift significantly towards the values typical for crowd-reared gregarized individuals. The results indicate that the corpora cardiaca contain a factor similar to [His⁷]-corazonin, although it has no dark-colour inducing activity.     

The Penn State Safety Floor: Part I--Design parameters associated with walking deflections.

A new flooring system has been developed to reduce peak impact forces to the hips when humans fall. The new safety floor is designed to remain relatively rigid under normal walking conditions, but to deform elastically when impacted during a fall. Design objectives included minimizing peak force experienced by the femur during a fall-induced impact, while maintaining a maximum of 2 mm of floor deflection during walking. Finite Element Models (FEMs) were developed to capture the complex dynamics of impact response between two deformable bodies. Validation of the finite element models included analytical calculations of theoretical buckling column response, experimental quasi-static loading of full-scale flooring prototypes, and flooring response during walking trials. Finite Element Method results compared well with theoretical and experimental data. Both finite element and experimental data suggest that the proposed safety floor can effectively meet the design goal of 2 mm maximum deflection during walking, while effectively reducing impact forces during a fall.     

Fracture of neck of the femur: changing incidence.

From 1959 to 1977 the numbers of hospital admissions for fracture of the neck of the femur increased by a factor of 2.7. Detailed analysis of data from the Hospital In-Patient Enquiry for 1968-77 showed that the increase applied to both sexes and at all ages over 45. The true incidence rate increased in parallel with the admission rate, and only a small part of the increased number of admissions was explained by the increasing numbers of the elderly. The increasing incidence of fracture of the neck of the femur imposes great strain on hospital resources, particularly trauma and orthopaedic departments, and merits urgent investigation. An explanation for the increase might be that the experience of one demand-led condition characterises a greater need for health care among the elderly for other conditions.     

A Three-Dimensional Musculoskeletal Model of the Human Knee Joint. Part 1: Theoretical Construction

A three-dimensional model of the knee is developed to study the interactions between the muscles, ligaments, and bones during activity. The geometry of the distal femur, proximal tibia, and patella is based on cadaver data reported for an average-size knee. The shapes of the femoral condyles are represented by high-order polynomials: the tibial plateaux and patellar facets are approximated as flat surfaces. The contacting surfaces of the femur and tibia are modeled as deformable, while those of the femur and patella are assumed to be rigid. Interpenetration of the femur and tibia is taken into account by modeling cartilage as a thin, linear, elastic layer, mounted on rigid bone. Twelve elastic elements describe the geometry and mechanical properties of the cruciate ligaments, the collateral ligaments, and the posterior capsule. The model is actuated by thirteen musculotendinous units, each unit modeled as a three-element muscle in series with tendon. The path of each muscle is approximated as a straight line, except where it contacts and wraps around bone and other muscles; changes in muscle paths are taken into account using data obtained from MRI. In the first part of this paper, the model is used to simulate passive knee flexion. Quantitative comparisons of the model results with experimental data reported in the literature indicate that the relative movements of the bones and the geometry of the ligaments and muscles in the model are similar to those evident in the real knee. In Part II, the model is used to describe knee-ligament function during anterior-posterior draw, axial rotation, and isometric knee-extension and knee-flexion exercises.     

A Three-Dimensional Musculoskeletal Model of the Human Knee Joint. Part 1: Theoretical Construct

A three-dimensional model of the knee is developed to study the interactions between the muscles, ligaments, and bones during activity. The geometry of the distal femur, proximal tibia, and patella is based on cadaver data reported for an average-size knee. The shapes of the femoral condyles are represented by high-order polynomials; the tibial plateaux and patellar facets are approximated as flat surfaces. The contacting surfaces of the femur and tibia are modeled as deformable, while those of the femur and patella are assumed to be rigid. Interpenetration of the femur and tibia is taken into account by modeling cartilage as a thin, linear, elastic layer, mounted on rigid bone. Twelve elastic elements describe the geometry and mechanical properties of the cruciate ligaments, the collateral ligaments, and the posterior capsule. The model is actuated by thirteen musculotendinous units, each unit modeled as a three-element muscle in series with tendon. The path of each muscle is approximated as a straight line, except where it contacts and wraps around bone and other muscles; changes in muscle paths are taken into account using data obtained from MRI. In the first part of this paper, the model is used to simulate passive knee flexion. Quantitative comparisons of the model results with experimental data reported in the literature indicate that the relative movements of the bones and the geometry of the ligaments and muscles in the model are similar to those evident in the real knee. In Part II, the model is used to describe knee-ligament function during anterior-posterior draw, axial rotation, and isometric knee-extension and knee-flexion exercises.     

Relative safety factors against global buckling, anchorage rotation, and tissue rupture in wheat.

The objective of this study was to quantify the effect of specific physical and biological factors on the relative likelihood of biomechanical failure in wheat. Wind-related crop damage is a major obstacle to wheat production that costs several billion dollars per year. The four factors varied in this study were breeding line, dwarfing gene dose, soil type, and fertilization. A theoretical model describing the dynamic structural response of living plants was used to define margins of safety against global buckling, anchorage rotation, and tissue rupture. These relative safety factors were defined for each treatment in comparison with a tall wheat variety selected from a breeding line called Seri and grown in sandy soil with low fertilization. Compared to this reference, the relative safety factor against global buckling was increased (+39%, p<0.01), and the relative safety factor against anchorage rotation was decreased (-11%, p<0.025), by one allele of the dwarfing gene. The relative safety factor against tissue rupture was unaffected by the dwarfing gene but was consistently lower (-26%, p<0.01) in a second breeding line called Kauz. Soil type and fertility did not affect the relative safety factors and this negative finding was significant at p<0.05. The key finding was that the strength of wheat was affected more by genetic rather than by environmental factors, which suggests that some varieties are intrinsically more robust than others. Also, the relative safety factor against anchorage rotation was inversely proportional to the relative safety factor against buckling, which suggests that there are competing constraints on the dynamic structural behavior of wheat.     

The critical size bony defect in a small animal for bone healing studies (I): Comparative anatomical study on rats' femur.

Laboratory rats are small animal models which are often used for scientific investigations in medicine. So far there are only few scientific data about the meaning of these small animal models for in vivo bone healing studies available in literature. Although the rat's femur with its cyclic loadings during gait is an appropriate model for investigations in the field of experimental orthopaedics and traumatology there is a lack of morphometric information with respect to its anatomy. The aim of this study is to evaluate the anatomy of rat femurs in two species, which are often performed in animal experimental medicine. These morphometric data should contribute to develope an appropriated osseous fragment fixation system in the rat's femur. The femurs of Wistar (WR) and Sprague Dawley (SDR) cadavers were prepared and analysed by x-rays in two standard planes. The results were compared with the corresponding data for humans by literature. It could be demonstrated that SDR showed a higher caput-collum-diaphyseal and antetorsion angle, but a lower transcondylar femur valgus angle compared to WR. Cortical thickness, bone marrow cavity diameter and femur length were higher in WR. Wistar rat's femur anatomy shows more similarities to human anatomy than Sprague Dawley rats.     

Legislative and technical aspects of mutagenicity testing.

A brief account is given of the history of the legislative acts that give responsibility to the U.S. Food and Drug Administration (FDA) for ensuring the safety of foods, drugs, and cosmetics. Within the present legislative framework the FDA has the authority to impose regulations which are designed to ensure the safety of all foods, drugs, and cosmetics. The existing legislative authority is adequate for this purpose; however, the difficulty lies instead with technology and the inadequacy of scientific perspective in the emerging area of mutagenicity testing. Earlier efforts in development of mutagenicity screening systems culminated only a few years ago in the proposal to use the host-mediated assay, somatic cell cytogenetics, and dominant lethal tests collectively. Subsequent research efforts indicated that there were serious practical and scientific deficiencies in using this approach. More recently a new proposal, the tier system, has been suggested as an alternative measure. The proposed tier system at FDA consists of three testing levels of increasing complexity. The first tier is an initial screening effort using techniques having maximum sensitivity that are also useful for large-scale, rapid testing. The second tier is designed to identify and confirm that the presumptive mutagens detected in the first tier are truly mutagenic for higher organisms, most especially, for mammals. The third tier would be devoted to explicit genetic tests in mammals designed to ascertain the imposed risk to man by the introduction of a mutagen in our environment. The FDA is currently involved in a number of research activities in the area of mutagenicity safety screening which will explore the adequacies and possible deficiencies of the tier system approach. These efforts are described for our in-house activities, our contract activities, and our cooperative and collaborative activities with other government agencies and institutions.     

The energetics of the jump of the locust Schistocerca gregaria.

The anatomy of the metathoracic leg is redescribed with particular reference to storage of energy in cuticular elements and the way in which the stored energy is used in jumping. The jump of adult male locusts requires an energy of 9 mJ and that of the female requires 11 mJ. The semilunar processes of each metafemur store 4 mJ at a stress of 15 N, and the extensor tibiae apodeme stores a further 3 mJ at the same stress. The total stored energy in both metathoracic legs is 14 mJ. The extensor tibiae muscle produces a maximum isometric force of over 15 N at 30 degrees C and, when loaded with the extensor apodeme and semilunar processes, attains this force in 0.3 sec with a strain of 0.8 mm. The peak power output is 36 mW or 0.45 W.g-1. The peak isometric force is attained when the tibia is fully flexed and the force falls as the tibia extends. The extensor tibiae muscle A band is 5.5 mum long and the peak force is over 0.75 N.m-2. The peak velocity of shortening is 7 mm.sec-1 or about 1.75 lengths/sec at 30 degrees C. The tensile strength of the extensor apodeme is 0.6 kN.mm-2 and Young's modulus is 19 kN.mm-2. The safety factor does not exceed 1.2 and the safety factor of the semilunar processes and tibial cuticle is little higher. The jump impulse lasts 25-30 msec. A velocity of 3.2 m.sec-1 is reached after a peak acceleration of 180 m.sec-2. The peak power output is 0.75 W at close to maximum velocity. Energy losses in rotating the femur and tibia are small and it is shown that the leg is able to extend at 7 times the normal rate with losses of about 20%. Most of the stored energy is converted to kinetic energy as the animal jumps. A model is based on the relaxation of a spring that has the properties of the elastic elements of the locust leg into a lever with the same kinematics as the locust leg produces a force-distance curve similar to that measured for locust jumps. The major part of the jump energy is stored before the jump.     

Anteversion versus torsion of the femoral neck.

The usual term 'torsion angle of the femur' denotes the 'anteversion' of the neck of the femur as a whole, caused by the twist in the shaft of the femur rather than the twist in the neck. This has been differentiated from the twist in the neck of the femur around its own axis, termed 'torsion neck' and the values of both have been measured. To differentiate these two different phenomena, the term 'anteversion' is used to denote the usual angel described, while 'torsion neck' is sued to denote the twist in the neck around its own axis measured in this work. 1,000 femora from 21 cites in different parts of the country have been measured and the average anteversion angle calculated. The Indian average works out to be 12 degrees with a significantly (double) high value for females. The incidence of negative angle is 7% in the normal femora. All fractured femora invariably show a negative angle. The above information should be of great significance on orthopaedic surgery of the neck of the femur in these bones. The 'torsion neck' has been measured by tracing and its average reported as 30 degrees.     

Correlation of muscle function and bone strain in the hindlimb of the river cooter turtle (Pseudemys concinna)

During terrestrial locomotion, limb muscles must generate mechanical work and stabilize joints against the ground reaction force. These demands can require high force production that imposes substantial loads on limb bones. To better understand how muscle contractile function influences patterns of bone loading in terrestrial locomotion, and refine force platform equilibrium models used to estimate limb bone safety factors, we correlated in vivo recordings of femoral strain with muscle activation and strain in a major propulsive hindlimb muscle, flexor tibialis internus (FTI), of a species with a published model of hindlimb force production (river cooter turtles, Pseudemys concinna). Electromyography (EMG) recordings indicate FTI activity prior to footfall that continues through approximately 50% of the stance phase. Large EMG bursts occur just after footfall when the muscle has reached its maximum length and is beginning to actively shorten, concurrent with increasing compressive strain on the anterior femur. The FTI muscle shortens through 35% of stance, with mean fascicle shortening strains reaching 14.0 ± 5.4% resting length (L₀). At the time of peak compressive strains on the femur, the muscle fascicles remain active, but fascicles typically lengthen until mid‐stance as the knee extends. Influenced by the activity of the dorsal knee extensor femorotibialis, the FTI muscle continues to passively lengthen simultaneously with knee extension and a shift to tensile axial strain on the anterior femur at approximately 40% of stance. The near coincidence in timing of peak compressive bone strain and peak muscle shortening (5.4 ± 4.1% stance) indicates a close correlation between the action of the hip extensor/knee flexor, FTI, and femoral loading in the cooter hindlimb. In the context of equilibrium models of limb bone loading, these results may help explain differences in safety factor estimates observed between previous force platform and in vivo strain analyses in cooters. J. Morphol. 274:1060–1069, 2013. © 2013 Wiley Periodicals, Inc.     

Effects of spirulina, a blue-green alga, on bone metabolism in ovariectomized rats and hindlimb-unloaded mice

The safety and effectiveness were examined of the spirulina alga on bone metabolism in ovariectomized estrogen-deficient rats and hindlimb-unloaded mice. The dosage range was from an amount equal to that recommended in so-called health foods for humans (0.08 g/kg BW/day) to a 100-fold higher dose. The bone mineral density (BMD) of the whole femur and tibia of ovariectomized rats in the any spirulina-treated groups was not significantly different from that of the ovariectomized group, although BMD of the distal femur and proximal tibia was significantly lower in the spirulina-treated groups than in the ovariectomized group after a 6 week-experimental period. BMD of the femur and tibia was not affected by treatment with any dose of spirulina in hindlimb-unloaded mice. These results suggest that the intake of spirulina decreased BMD in the trabecular bone of rodents under estrogen-deficient conditions.     

Zinc and copper of fetal organs during the second trimester of pregnancy

In fetus with a mean gestational age of 18 weeks (range 15-25, n = 14), zinc and copper concentrations in liver, femur, rib, and skeletal muscle were measured. Zinc and copper concentrations are highest in liver. A trend of decreasing liver zinc concentrations during gestational age is suggested. Zinc concentrations are significantly correlated with copper concentrations in liver and in femur, suggesting steady growth in both organs. Femur zinc values rank ca. 30% of those in liver, femur copper, ca. 2%. Zinc or copper concentrations in rib are of the same levels as in skeletal muscle. Their concentration for zinc ranks ca. 20%, for copper, ca. 5% of the values in liver. All zinc and copper values are lower than reported in third trimester fetal organs. Calculated zinc/copper molar ratios are distinctive for the various organs: in liver, 6 +/- 1, in femur, 73 +/- 8, and in soft tissues, 26 +/- 3. Calculated ratios from published values obtained from the third trimester of pregnancy show that the ratios in liver and skeletal muscle maintain these levels. The zinc/copper molar ratio can serve as an internal reference in zinc and/or copper measurements.     

A new highly specialized cave harvestman from Brazil and the first blind species of the genus: Iandumoema smeagol sp. n. (Arachnida,Opiliones, Gonyleptidae)

A new species of troglobitic harvestman, Iandumoema smeagol sp. n., is described from Toca do Geraldo, Monjolos municipality, Minas Gerais state, Brazil. Iandumoema smeagol sp. n. is distinguished from the other two species of the genus by four exclusive characteristics – dorsal scutum areas with conspicuous tubercles, enlarged retrolateral spiniform tubercle on the distal third of femur IV, eyes absent and the penial ventral process slender and of approximately the same length of the stylus. The species is the most highly modified in the genus and its distribution is restricted only to caves in that particular area of Minas Gerais state. The type locality is not inside a legally protected area, and there are anthropogenic impacts in its surroundings. Therefore, Iandumoema smeagol sp. n. is vulnerable and it must be considered in future conservation projects.     

Stress analysis of the proximo-medial femur after total hip replacement

Stress-induced bone loss in the proximo-medial femur has been identified as a factor leading to loosening in the artificial hip joint. In an effort to develop a quantitative understanding of the stress distribution that causes bone loss, axial and hoop stresses in the medial calcar of the femur have been determined after total hip replacement, using finite element stress analysis. Stress distributions for a high and a low Young's modulus prosthesis material are compared for both collared and uncollared prosthesis designs. The use of a low-modulus material, and of a collar, are predicted to be advantageous, giving rise to proximo-medial stress patterns similar to those of the normal, intact femur.