Genetic loci influencing natural variations in femoral bone morphometry in mice.

This study identifies genetic loci affecting femoral bone length and width measures in mature mice. Sixteen month old female F2 progeny of a C57BL/6J and DBA/2J intercross were examined for femur length and width of the femoral head, intertrochanteric region and three locations of the diaphysis using digitized images of femur radiographs obtained in the anterior-posterior and lateral projections. A genome wide linkage map was constructed using microsatellite markers at an average density of 20 cM, and quantitative trait locus analysis used to identify regions of the genome showing linkage with the traits measured. Femur length showed significant linkage with loci on proximal chromosome 3 (lod 6.1), and suggestive linkage with a locus on chromosome 14. A major locus on mid-chromosome 7 controlled width of the diaphysis (lod 6.8). Other loci were identified on chromosomes 2 and 4. Width at the intertrochanteric region had suggestive linkage with loci on chromosomes 6 and 19. No loci were found with linkage for width of the femoral head. Candidate genes related to bone development or metabolism are present at most of these loci. These findings show that genetic regulation of femoral bone morphology is complex, and are consistent with the distinct biologic processes that control longitudinal and lateral growth of the femur.

Genetic loci determining bone density in mice with diet-induced atherosclerosis.

This study investigates the phenotypic and genetic relationships among bone-density-related traits and those of adipose tissue and plasma lipids in mice with diet-induced atherosclerosis. Sixteen-month-old female F2 progeny of a C57BL/6J and DBA/2J intercross, which had received an atherogenic diet for 4 mo, were examined for multiple measures of femoral bone mass, density, and biomechanical properties using both computerized tomographic and radiographic methods. In addition, body weight and length, adipose tissue mass, plasma lipids and insulin, and aortic fatty lesions were assessed. Bone mass was inversely correlated with extent of atherosclerosis and with a prooxidant lipid profile and directly correlated with body weight, length, and, most strongly, adipose tissue mass. Quantitative trait locus (QTL) analysis, using composite interval mapping (CIM) and multi-trait analysis, identified six loci with multi-trait CIM LOD scores > 5. Three of these coincided with loci linked with adipose tissue and plasma high-density lipoprotein. Application of statistical tests for distinguishing close linkage vs. pleiotropy supported the presence of a potential pleiotropic effect of two of the loci on these traits. This study shows that bone mass in older female mice with atherosclerosis has multiple genetic determinants and provides phenotypic and genetic evidence linking the regulation of bone density with adipose tissue and plasma lipids.

Mechanisms of load transfer in the cadaver forearm: role of the interosseous membrane.

Forces transmitted through the distal ulna and proximal radius, relative motion between the radial head and capitellum, and measurements of tissue strain and local fiber tension within the central band of the interosseous membrane were recorded as cadaveric forearms were loaded axially through the wrist. With the elbow in valgus alignment (the radial head in direct contact with the capitellum), an average of 93% of force applied to the wrist was transferred directly through the radius to the elbow with no appreciable load transfer through the interosseous membrane. With varus alignment (initial gap between the radial head and capitellum) load applied to the wrist displaced the radius proximally an average of 1.1 mm until radial head contact occurred at a mean applied wrist force of 89.0 N. Proximal displacement of the radius generated strain in the central band of the interosseous membrane and created a more ulnar positive wrist, which in turn increased distal ulnar loading; distal ulnar force averaged 19% and interosseous membrane averaged 54% of applied wrist force. Distal ulnar loading was unaffected by 25 degrees wrist flexion-extension or by 20 degrees of radioulnar deviation. With 40 degrees ulnar deviation, mean distal ulnar forces were 18% and 48% of applied wrist force for valgus and varus elbow alignments, respectively. Mean load-sharing percentages at the wrist and elbow were not significantly different between 222. 5 N and 133.5 N of applied force for any wrist position and were unaffected by the angle of elbow flexion.

Scaphocapitate syndrome in a child associated with a distal radius and ulna fracture.

A case is presented of scaphocapitate fracture syndrome associated with a Salter-Harris type II fracture of the distal radius and ulna occurring in an 11-year-old girl. The proximal fragment of the fractured capitate was rotated 180 degrees. The injury was treated by open reduction and internal fixation. One year after the injury, radiographs showed that fractures were united with no signs of avascular necrosis of the capitate. The patient had a full range of motion of the wrist, as well as full pronation and supination of the forearm. An awareness of this fracture entity is necessary to correctly diagnose this injury in a child.

Microanatomy of the orbital apex. Computed tomography and microcryoplaning of soft and hard tissue.

PURPOSE: The anatomy of the orbital apex is characterized by a complex interplay between critical bony and neural structures. Traditional methods used to study this region include dissection, static sections, and computed tomography (CT). Tomographic techniques are very useful in understanding these complex relationships, but the resolution of conventional CT and magnetic resonance imaging (MRI) is not sufficient to recognize the intricate details of the optic nerve canal and associated structures. The purpose of this study is to determine the value of microcryoplaning and computer reconstruction in visualizing the orbital apex in detail not previously possible, at any orientation in three-dimensional space. METHODS: Microcryotomy of the orbital apex area was performed on cadaver specimens, and images of each cryosection were digitized. Subsequently, the lesser wing of sphenoid bone and optic nerve were outlined to allow for spatial manipulation and three-dimensional visualization of the orbital apex. RESULTS: The authors present reconstructed computer images of the orbital apex in coronal and axial planes with CT correlation. Clinically important anatomic points and landmarks as well as potential pitfalls are demonstrated. CONCLUSION: Microcryoplaning and computer reconstruction are useful techniques in viewing the detailed anatomy of the orbital apex. Although microcryoplaning has the limitation of poor soft tissue detail, the resolution of captured images is much greater than those obtained from CT or MRI scans; the improved resolution allows for accurate CT correlations. The technique has utility in education, surgical planning, and quantitative analysis of orbital apical anatomy.

Minimally oxidized low-density lipoprotein induces tissue factor expression in cultured human endothelial cells.

Oxidatively modified low-density lipoprotein is present in atherosclerotic lesions and has been proposed to play an important role in atherogenesis through its biologic effects on vascular cells. This study examined the effects of minimally oxidized preparations of LDL (MM-LDL) on tissue factor (TF) expression by cultured human endothelial cells. Low-density lipoprotein purified from normal donors was modified by exposure to iron or by prolonged storage, resulting in levels of thiobarbituric acid-reacting substances of approximately 2.5 to 4 nmoles/mg cholesterol. Preparations had less than 2.5 pg of endotoxin per microgram LDL and had no intrinsic procoagulant activity. This form of modified but not native LDL induced TF expression in endothelial cells in a time- and dose-dependent manner. Peak TF coagulant activity in cells exposed to 40 micrograms/ml MM-LDL were observed at 4 to 6 hours, and ranged from 50 to 500 pg/10(5) cells, compared with less than 10 pg/10(5) cells exposed to native LDL. Northern blot analysis showed TF mRNA levels to increase approximately 30-fold with exposure to MM-LDL for 2 hours. Induction of TF activity was dependent on the concentration of MM-LDL from 1 microgram/ml to 80 micrograms/ml, a range in which cell viability and morphology were unaffected. The findings suggest that minimally oxidized LDL may be a local mediator promoting thrombosis in atherosclerotic lesions.