@article{levine_cianciolo_linder_bizikova_birkenheuer_brooks_salous_nordone_bellinger_marr_et al._2017, title={Endothelial alterations in a canine model of immune thrombocytopenia}, volume={30}, ISSN={0953-7104 1369-1635}, url={http://dx.doi.org/10.1080/09537104.2017.1378807}, DOI={10.1080/09537104.2017.1378807}, abstractNote={Bleeding heterogeneity amongst patients with immune thrombocytopenia (ITP) is poorly understood. Platelets play a role in maintaining endothelial integrity, and variable thrombocytopenia-induced endothelial changes may influence bleeding severity. Platelet-derived endothelial stabilizers and markers of endothelial integrity in ITP are largely underexplored. We hypothesized that, in a canine ITP model, thrombocytopenia would lead to alterations in the endothelial ultrastructure and that the Von Willebrand factor (vWF) would serve as a marker of endothelial injury associated with thrombocytopenia. Thrombocytopenia was induced in healthy dogs with an antiplatelet antibody infusion; control dogs received an isotype control antibody. Cutaneous biopsies were obtained prior to thrombocytopenia induction, at platelet nadir, 24 hours after nadir, and on platelet recovery. Cutaneous capillaries were assessed by electron microscopy for vessel thickness, the number of pinocytotic vesicles, the number of large vacuoles, and the number of gaps between cells. Pinocytotic vesicles are thought to represent an endothelial membrane reserve that can be used for repair of damaged endothelial cells. Plasma samples were assessed for vWF. ITP dogs had significantly decreased pinocytotic vesicle numbers compared to control dogs (P = 0.0357) and the increase in plasma vWF from baseline to 24 hours correlated directly with the endothelial large vacuole score (R = 0.99103; P < 0.0001). This direct correlation between plasma vWF and the number of large vacuoles, representing the vesiculo-vacuolar organelle (VVO), a permeability structure, suggests that circulating vWF could serve as a biomarker for endothelial alterations and potentially a predictor of thrombocytopenic bleeding. Overall, our results indicate that endothelial damage occurs in the canine ITP model and variability in the degree of endothelial damage may account for differences in the bleeding phenotype among patients with ITP.}, number={1}, journal={Platelets}, publisher={Informa UK Limited}, author={LeVine, Dana N. and Cianciolo, Rachel E. and Linder, Keith E. and Bizikova, Petra and Birkenheuer, Adam J. and Brooks, Marjory B. and Salous, Abdelghaffar K. and Nordone, Shila K. and Bellinger, Dwight A. and Marr, Henry and et al.}, year={2017}, month={Nov}, pages={88–97} }
 @article{gulledge_marcellin-little_levine_tillman_harrysson_osborne_baxter_2014, title={Comparison of two stretching methods and optimization of stretching protocol for the piriformis muscle}, volume={36}, ISSN={1350-4533}, url={http://dx.doi.org/10.1016/J.MEDENGPHY.2013.10.016}, DOI={10.1016/j.medengphy.2013.10.016}, abstractNote={Piriformis syndrome is an uncommon diagnosis for a non-discogenic form of sciatica whose treatment has traditionally focused on stretching the piriformis muscle (PiM). Conventional stretches include hip flexion, adduction, and external rotation. Using three-dimensional modeling, we quantified the amount of (PiM) elongation resulting from two conventional stretches and we investigated by use of a computational model alternate stretching protocols that would optimize PiM stretching. Seven subjects underwent three CT scans: one supine, one with hip flexion, adduction, then external rotation (ADD stretch), and one with hip flexion, external rotation, then adduction (ExR stretch). Three-dimensional bone models were constructed from the CT scans. PiM elongation during these stretches, femoral neck inclination, femoral head anteversion, and trochanteric anteversion were measured. A computer program was developed to map PiM length over a range of hip joint positions and was validated against the measured scans. ExR and ADD stretches elongated the PiM similarly by approximately 12%. Femoral head and greater trochanter anteversion influenced PiM elongation. Placing the hip joints in 115° of hip flexion, 40° of external rotation and 25° of adduction or 120° of hip flexion, 50° of external rotation and 30° of adduction increased PiM elongation by 30-40% compared to conventional stretches (15.1 and 15.3% increases in PiM muscle length, respectively). ExR and ADD stretches elongate the PiM similarly and therefore may have similar clinical effectiveness. The optimized stretches led to larger increases in PiM length and may be more easily performed by some patients due to increased hip flexion.}, number={2}, journal={Medical Engineering & Physics}, publisher={Elsevier BV}, author={Gulledge, Brett M. and Marcellin-Little, Denis J. and Levine, David and Tillman, Larry and Harrysson, Ola L.A. and Osborne, Jason A. and Baxter, Blaise}, year={2014}, month={Feb}, pages={212–218} }
 @inproceedings{sawaya_combet_chanoit_thiebault_levine_marcellin-little_2008, title={Assessment of impulse duration thresholds for electrical stimulation of muscles (chronaxy) in dogs}, volume={69}, DOI={10.2460/ajvr.69.10.1305}, abstractNote={Abstract Objective —To determine the electrical impulse duration thresholds (chronaxy) for maximal motor contraction of various muscles without stimulation of pain fibers in dogs. Animals —10 healthy adult Beagles. Procedures —The dogs were used to assess the minimal intensity (rheobase) required to elicit motor contraction of 11 muscles (5 in the forelimb [supraspinatus, infraspinatus, deltoideus, lateral head of the triceps brachii, and extensor carpi radialis], 5 in the hind limb [gluteus medius, biceps femoris, semitendinosus, vastus lateralis, and tibialis cranialis], and the erector spinae). The rheobase was used to determine the chronaxy for each of the 11 muscles in the 10 dogs; chronaxy values were compared with those reported for the corresponding muscles in humans. Results —Compared with values in humans, chronaxy values for stimulation of AA motor fibers in the biceps femoris and semitendinosus muscles and muscles of the more distal portions of limbs were lower in dogs. For the other muscles evaluated, chronaxy values did not differ between dogs and humans. Conclusions and Clinical Relevance —Application of the dog-specific chronaxy values when performing electrical stimulation for strengthening muscles or providing pain relief is likely to minimize the pain perceived during treatment in dogs.}, number={10}, booktitle={American Journal of Veterinary Research}, author={Sawaya, S. G. and Combet, D. and Chanoit, G. and Thiebault, J. J. and Levine, D. and Marcellin-Little, D. J.}, year={2008}, pages={1305–1309} }