Vikram Sathyendra’s research while affiliated with United States Steel and other places

Background: Optimal femoral fixation of soft-tissue grafts has been described for anterior cruciate ligament reconstruction. Posterolateral corner reconstruction differs from ACL reconstruction in two ways: (a) soft-tissue fixation into the femur requires two tails and (b) the line of force is different. Our purpose was to determine the optimal femoral fixation of soft-tissue grafts during posterolateral corner reconstructions. We hypothesized that interference screw fixation is the strongest technique in normal-density lateral femoral condyle, whereas, cortically-based fixation techniques are stronger methods in low-density lateral femoral condyle. Methods: We evaluated elongation during cyclic loading, yield load, peak load-to-failure, and stiffness of four soft-tissue graft femoral fixation methods during posterolateral corner reconstruction. Our model included bovine flexor tendons and contoured synthetic bones. Grafts were secured to the lateral epicondyle in normal- or low-density bone models using spiked washer, button, interference screw, or button and interference screw. Five specimens for each were tested in each bone density. Analysis of variance using Tukey-Kramer adjustment for multiple hypothesis testing was used. Six cadaver bones whose density was analyzed using computerized tomography scan quantitation were tested using interference screw fixation. Results: No method produced significantly stronger yield load or peak load-to-failure in normal-density bone. In low-density bone, cortically-based methods produced significantly higher yield load or peak load-to-failure. Yield load or peak load-to-failure was significantly higher in normal-density bone when using spiked washer or interference screw fixation. Conclusion: No femoral fixation method tested produced superior yield load or peak load-to-failure. Spiked washer and interference screw fixation are inferior fixation methods in low-density bone. Clinical relevance: For fibular-based posterolateral corner reconstructions, all fixation methods tested are acceptable in high-density bone, while cortical fixation methods should be considered in low-density bone.

Background: We propose that fracture-healing potential is affected by the patient's genome. This genotype is then phenotypically expressed by the patient at the time of injury. We examined the hypothesis that patients who exhibit delayed or impaired fracture-healing may have one or more single nucleotide polymorphisms (SNPs) within a series of genes related to bone formation. Methods: We performed a population-based, case-controlled study of delayed fracture-healing. Sixty-two adults with a long-bone fracture were identified from a surgical database. Thirty-three patients had an atrophic nonunion (delayed healing), and twenty-nine displayed normal fracture-healing. These patients underwent buccal mucosal cell harvesting. SNP genotyping was performed with use of bead array technology. One hundred and forty-four SNPs (selected from HapMap) within thirty genes associated with fracture-healing were investigated. Three SNPs did not segregate in the population and were excluded from the analysis. Eight of the remaining SNPs failed the test for Hardy-Weinberg equilibrium (p value smaller than the Bonferroni-corrected level of 0.05/141 = 0.000355) and were excluded. Results: Five SNPs on four genes were found to have a p value of <0.05 in the additive genetic model. Of these five significant SNPs, three had an odds ratio (OR) of >1, indicating that the presence of the allele increased the risk of nonunion. The rs2853550 SNP, which had the largest effect (OR = 5.9, p = 0.034), was on the IL1B gene, which codes for interleukin 1 beta. The rs2297514 SNP (OR = 3.98, p = 0.015) and the rs2248814 SNP (OR = 2.27, p = 0.038) were on the NOS2 gene coding for nitric oxide synthase. The remaining two SNPs had an OR of <1, indicating that the presence of the allele may be protective against nonunion. The rs3819089 SNP (OR = 0.26, p = 0.026) was on the MMP13 gene for matrix metallopeptidase 13, and the rs270393 SNP (OR = 0.30, p = 0.015) was on the BMP6 gene for bone morphogenetic protein 6. Conclusions: Variations in the IL1B and NOS2 genes may contribute to delayed fracture-healing and warrant further investigation. Clinical relevance: Impaired fracture union may have genetic contributions.

Bone healing is a complex process that can be influenced by both host and environmental factors. In this article, we review the biology involved in the regeneration of new bone after fracture, and factors influencing bone healing, including diabetes, smoking, NSAID use, and bisphosphonates.

Grip lock injuries are uncommon, potentially devastating occurrences in male gymnasts performing high bar routines, and typically cause severe wrist sprains or forearm fractures. We retrospectively reviewed medical records of a 24-year-old former collegiate gymnast surgically treated for complete loss of index and long finger extension (pseudorupture) after a grip lock injury. Intraoperative evaluation 3 weeks after injury revealed profound intratendinous attenuation of index and long finger extensors with adhesions in the fourth compartment. We performed tenolysis and imbrication of the affected tendons. At 12-month follow-up, the patient had no pain, full digital range of motion with the wrist in neutral, but residual extensor lag with the wrist in extension. He had returned to gymnastics with some apprehension. This case broadens the known spectrum of grip lock injuries.

Emerging evidence suggests that connexin mediated gap junctional intercellular communication contributes to many aspects of bone biology including bone development, maintenance of bone homeostasis and responsiveness of bone cells to diverse extracellular signals. Deletion of connexin 43, the predominant gap junction protein in bone, is embryonic lethal making it challenging to examine the role of connexin 43 in bone in vivo. However, transgenic murine models in which only osteocytes and osteoblasts are deficient in connexin 43, and which are fully viable, have recently been developed. Unfortunately, the bone phenotype of different connexin 43 deficient models has been variable. To address this issue, we used an osteocalcin driven Cre-lox system to create osteoblast and osteocyte specific connexin 43 deficient mice. These mice displayed bone loss as a result of increased bone resorption and osteoclastogenesis. The mechanism underlying this increased osteoclastogenesis included increases in the osteocytic, but not osteoblastic, RANKL/OPG ratio. Previous in vitro studies suggest that connexin 43 deficient bone cells are less responsive to biomechanical signals. Interestingly, and in contrast to in vitro studies, we found that connexin 43 deficient mice displayed an enhanced anabolic response to mechanical load. Our results suggest that transient inhibition of connexin 43 expression and gap junctional intercellular communication may prove a potentially powerful means of enhancing the anabolic response of bone to mechanical loading.

Calbindin-D(28k) (CB), calretinin (CRT), and parvalbumin (PV) are high-affinity cytosolic calcium (Ca(2+)) binding proteins (CBP) that have been found to regulate intracellular calcium concentrations in neurons through their buffering capacity and to protect neurons from insults that induce elevations of intracellular Ca(2+). In earlier studies we observed a substantial and neurochemically specific loss of CB from the human basal forebrain cholinergic neurons (BFCN) in the course of normal aging. In the present experiments we expanded our investigation of age-related changes in calcium binding proteins in the human brain by investigating the status of CB-, CRT-, and PV-positive neurons in 17 cortical areas. There was a trend toward a decrease in the number of CB-immunoreactive neurons in all areas studied. However, this trend reached significance in only 4 areas in which the loss of CB-positive neurons ranged between 20 and 46%. Immunoreactivity for CRT was also decreased in many areas and this difference reached significance in three regions (26-37%). Cortical neurons displaying PV immunoreactivity did not show an age-related change. Comparison with other neurochemically specific cortical neurons indicated a similar age-related loss of nonphosphorylated neurofilament and NADPH-d activity in only a few cortical areas. In contrast, neuronal acetylcholinesterase activity was increased in a few cortical areas. These observations indicate that loss of CBP-positive neurons occurs in restricted cortical regions and is not a specific change as other neurochemically specific neurons also display restricted age-related changes. Furthermore, the age-related changes in cortical CBP-positive neurons appear to be considerably smaller than similar changes in the BFCN. The age-related depletion of CBPs is likely to deprive neurons from the capacity to buffer intracellular calcium and thus to leave them vulnerable to pathological processes that can cause increased intracellular calcium and lead to their degeneration.