Quantifying the Relationship Between the Transverse Acetabular Ligament and the Radiographic Teardrop.

BACKGROUND: The transverse acetabular ligament (TAL) has been described as an anatomic landmark to guide in the positioning of the acetabular component during total hip arthroplasty. On plain films, the radiographic teardrop (RT) has similarly been used as a measure of appropriate cup positioning. The goal of this study is to quantify the distance and location between the anatomic TAL and RT landmarks to aid in the positioning of acetabular component. METHODS: Sixteen randomly selected cadaveric pelvises (eight males, eight females) underwent dissection. Radiographic markers were placed bilaterally at the anteromedial insertions of the TAL, and true anteroposterior pelvic radiographs of the cadavers were obtained. Distances between the markers and the lateral borders of the RT were measured. RESULTS: The mean distance between the anteromedial insertion of the TAL and the lateral border of the RT in the male specimens was 11.8 (99% confidence interval, 11.4-12.2) mm. In the female specimens, the TAL to RT distance was shorter, with a mean of 8.4 (99% CI, 7.2-9.6) mm. There was a statistically significant difference between male and female cadavers (P < .01). CONCLUSION: The distance between the RT and TAL differs between males and females. Understanding the distance between these anatomic and radiographic landmarks should aid surgeons in obtaining a more accurate degree of acetabular component medialization and can serve as a guide to minimize overmedialization in order to achieve more accurate and reproducible placement of acetabular components during a total hip arthroplasty.

Accuracy of computer-navigated total hip arthroplasty.

Proper acetabular cup orientation is essential in total hip arthroplasty. The purpose of this study was to evaluate the accuracy of a particular imageless computer navigation system in determining cup position. Thirty-nine computer-navigated total hip arthroplasty intraoperative measurements of cup abduction and anteversion were compared with those from follow-up radiographs. Sensitivity, specificity, accuracy, prevalence-adjusted positive value (PPV), and negative predictive value were calculated for both navigation and radiographs. Navigation measurements had high specificity and PPV when assessing cup abduction and anteversion (specificity >90%, PPV >94%). In contrast, the system was not very effective in detecting suboptimal cup position (sensitivity abduction, 50%; anteversion, 33%). Intraoperative navigation readings in the safe zone have high probability of indicating correct placement. However, confirmation of suboptimal cup position intraoperatively requires additional diagnostic methods.

Range of motion following percutaneous fixation of pediatric supracondylar humerus fracture is independent of anterior osseous fragment resorption.

The objective of this study was to understand postoperative resorption of the anterior osseous fragment following closed reduction and percutaneous pinning (CRPP) of pediatric supracondylar humerus fractures and its effect on final range of motion (ROM). Eighty-six patients that underwent CRPP had sagittal and or axial plane deformities resulting in an anterior fragment. Humerocapitellar angle (HCA), anterior humeral line (AHL) and angle of rotation (AoR) were measured. A total of 11 (12.8%) patients failed to resorb the anterior fragment, 10 (90.9%) had satisfactory ROM. HCA initially was acceptable in 40 (46.5%) patients, and 37 (92.5%) demonstrated acceptable ROM. Final HCA was acceptable in 44 (51.2%) patients and 42 (95.4%) had acceptable final ROM. AHL was in the anterior third of the capitellum in 35 (40.6%) patients and 33 (94.3%) had acceptable ROM. Final AHL was in the anterior third of the capitellum in 43 (50.0%) patients and 41 (95.3%) had acceptable final ROM. No difference was found between acceptable ROM and HCA or AHL at either follow-up. Sixty-five and 21 patients had an AoR of 0° and between 23 and 36°, respectively. A total of 59 (90.7%) patients with an AoR of 0°, and 18 (85.7%) patients with an AoR of 23-36° displayed acceptable ROM. A total of 57 (87.7%) patients with an AoR of 0° and 18 (85.7%) with an AoR of 23-36° resorbed the anterior fragment. No association was found between rotational deformity and postoperative ROM or fragment resorption. Postoperative sagittal and axial plane alignment, HCA, AHL, AoR and resorption of the anterior osseous fragment does not correlate with final ROM.

Osteosarcoma cells differentiate into phenotypes from all three dermal layers.

BACKGROUND: Osteosarcomas are the most common solid malignant bone tumors, but little is known of their origin. The embryonal rest hypothesis views cancer cells as arising from committed progenitor stem cells in each tissue. Adult tissue contains primitive stem cells that retain the ability to differentiate across dermal lines, raising the possibility that the stem cell of origin of cancers may be from a more primitive stem cell than a progenitor. QUESTIONS/PURPOSES: Can osteosarcoma cells, when cultured under conditions used for multipotent stem cells, be induced to differentiate into multiple phenotypes, including those of the three different dermal lineages: mesodermal, ectodermal, and endodermal? METHODS: One rat and one human osteosarcoma cell line were cultured and treated with concentrations of 0, 10(-10), 10(-9), 10(-8), 10(-7), and 10(-6) mol/L dexamethasone for 5 weeks. Seventeen phenotypes were assayed either by tissue-specific histochemical stains or antibodies to tissue-specific proteins. Each phenotype was tested across all dexamethasone concentrations for each cell line and each phenotype was tested in three separate experiments with induction by dexamethasone RESULTS: Rat osteosarcoma (ROS) 17/2.8 and human osteosarcoma cell line U-2 show the appearance of cells that have markers for (1) mesodermal phenotypes such as bone, cartilage, skeletal muscle, and endothelial cells, (2) ectodermal phenotypes such as astrocytes, oligodendrocytes, neurons, and keratinocytes, and (3) an endodermal phenotype, hepatocytes. This indicates osteosarcomas are composed, at least in part, of primitive stem cells capable of differentiating into tissues from all three dermal lineages. CLINICAL RELEVANCE: If osteosarcomas arise from primitive stem cells, then treatment of osteosarcomas with exogenous differentiation agents may cause the stem cells to differentiate, thus halting their proliferation and stopping tumor growth.

Post-traumatic cervical spine epidural hematoma: Incidence and risk factors.

BACKGROUND: The incidence and risk factors for post-traumatic cervical epidural hematoma are not well described in the current literature. Our aim was to determine the incidence and associated risk factors for post-traumatic cervical spine epidural hematoma (SEH). METHODS: We performed a retrospective review of our institution's prospectively collected data submitted to the state trauma registry, using ICD-9 codes, for all patients activated as a trauma with cervical spine injuries, between the years 2010 and 2014. Patients with MRI available were classified based on the presence of cervical epidural hematoma (CEH) or no hematoma (NEH). For our second analysis, we classified patients with cord compression associated with an epidural hematoma (CC) and no cord compression (NCC). Potential risk factors evaluated included: INR, PTT, albumin and platelets levels, radiographic findings of Ankylosing Spondylitis (AS), and ISS. No conflicts of interest exist and/or funding was used for this study. RESULTS: 497 out of 1810 trauma activations met our inclusion criteria. 46 patients (2.5%) were found to have a post-traumatic cervical SEH (CEH). Of the CEH cohort, 76% were male, with 72% Caucasian, and a mean age of 55 years. 27 patients (5.4%) were found to have cervical cord compression at the level of the SEH. Of the CC arm, 78% were male, with 67% Caucasian, and a mean age of 56 years. A higher ISS and an elevated INR were found to be associated with epidural hematoma causing cord compression. CONCLUSIONS: An incidence of 2.5% is reported for post-traumatic cervical spine epidural hematoma. Of these, 59% had associated spinal cord compression. Patients with a higher ISS and elevated INR levels are at a higher risk for developing this potentially devastating.

Human stem cells isolated from adult skeletal muscle differentiate into neural phenotypes.

Multipotent neural stem cells have been isolated from the adult [Kirschenbaum B, Nedergaard M, Preuss A, Barami K, Fraser RA, Goldman SA. In vitro neuronal production and differentiation by precursor cells derived from the adult human forebrain. Cereb Cortex 1994;4(6):576-89; Laywell ED, Kukekov VG, Steindler DA. Multipotent neurospheres can be derived from forebrain subependymal zone and spinal cord of adult mice after protracted postmortem intervals. Exp Neurol 1999;156:430-3; Pluchino S, Quattrini A, Brambilla E, Gritti A, Salani G, Dina G, et al. Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis. Nature 2003;422:688-94] and embryonic [Vescovi AL, Parati EA, Gritti A, Poulin P, Ferrario M, Wanke E, et al. Isolation and cloning of multipotential stem cells from the embryonic human CNS and establishment of transplantable human neural stem cell lines by epigenetic stimulation. Exp Neurol 1999;156:71-83] central nervous system (CNS). In addition, neural cells can be obtained from sources other than the CNS by differentiating stem cells from a non-neural source down a neural lineage. This has previously been performed with pluripotent embryonic stem cells and adult stem cells derived from rat bone marrow [Woodbury D, Schwarz EJ, Prockop DJ, Black IB. Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res 2000;61:364-70; Woodbury D, Reynolds K, Black IB. Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis. J Neurosci 2002;69(6):908-17] and skeletal muscle [Romero-Ramos M, Vourc'h P, Young HE, Lucas PA, Wu Y, Chivatakarn O, et al. Neuronal differentiation of stem cells isolated from adult muscle. J Neurosci Res 2002;69:894-907]. Previously, we have isolated adult stem cells from human skeletal muscle with the potential to differentiate into mesoderm, ectoderm, and endoderm. The following in vitro experiments were designed to determine whether human adult stem cells behaved similarly to rat adult stem cells when both were isolated from skeletal muscle by the same procedure [Romero-Ramos M, Vourc'h P, Young HE, Lucas PA, Wu Y, Chivatakarn O, et al. Neuronal differentiation of stem cells isolated from adult muscle. J Neurosci Res 2002;69:894-907] and subjected to the same protocols to induce neurogenesis. The neural phenotypes that were created through the neurococktail or neurosphere protocol were analyzed for neural characteristics through morphology and immunohistochemistry antibody labeling for proteins to neurons (RT-97, beta-tubulin III, NF-160, NF-200, and synapsin), oligodendrocytes (CNPase and RIP), and astrocytes (GFAP). A calcium uptake assay also showed response to the neuronal excitotoxic agent glutamic acid. In conclusion, the neural differentiated stem cells derived from adult skeletal muscle may be a less invasive alternative for the treatment of CNS disorders over CNS derived neural stem cells.

No Soldier Left Behind: The Veterans Court Solution.

This paper concerns one of the newer iterations of problem-solving courts: veterans treatment courts. We trace the history of problem solving court implementation and explore the functioning of an established veterans court. The focus of this exploratory, qualitative study is the courthouse workgroup and their interactions both within the veterans court and with more traditional criminal courts and criminal justice agencies. We summarize the literature on problem solving courts and the experience, insights and suggestions of the members of the court we examined.

Transplantation of multipotent cells extracted from adult skeletal muscles into the subventricular zone of adult rats.

Stem cells isolated from adult tissues may be useful for autologous cell therapy in the nervous system. In the present study we tested the ability of multipotent stem cells isolated from adult muscle to survive and respond to migratory and differentiating cues when transplanted into the adult subventricular zone (SVZ). Prior to transplantation the cells were grown as spheres that expressed doublecortin, nestin, and betaIII-tubulin, as well as the mRNAs for the receptor EphA4 and the ligands ephrin B1, ephrin B2, but not ephrin B3. Four weeks after transplantation into the anterior part of the SVZ in adult rats, surviving cells were observed along the ventricular wall, in the SVZ, and in the posterior rostral migratory stream (RMS). None of these cells stained for betaIII-tubulin or doublecortin, which are molecules expressed by migrating neuroblasts, and none were present in the more rostral regions of the RMS or the olfactory bulb. However, most surviving transplanted cells were integrated into the wall of the lateral ventricle and expressed vimentin, a marker also expressed by ependymocytes. No tumors were observed 4 weeks posttransplantation. Our results suggest that multipotent stem cells isolated from adult muscle, which can be easily and safely isolated from patients and rapidly expanded ex vivo, may provide autologous vectors for the local delivery of secreted factors to the ventricles or nearby regions.

Outcome following open reduction and internal fixation of open pilon fractures.

BACKGROUND: A variety of treatment options exist for open pilon fractures of the distal end of the tibia. In this study, we evaluated the use of a staged protocol designed to minimize the risk of soft-tissue complications and to allow for optimal reduction of the fracture. METHODS: Sixty-eight patients presenting with an open pilon fracture were identified from a prospectively maintained database of 186 consecutive patients. Fifty-nine of the sixty-eight patients, with an average age of forty-seven years, were followed for an average of thirty-four months and formed the study cohort. Within this group, there were two grade-I, three grade-II, thirty-seven grade-IIIA, and seventeen grade-IIIB open injuries. Clinical and radiographic outcomes were assessed by individuals not involved in the treatment of the patients. Functional outcome was assessed, with use of the modified Mazur scoring system and Short Form-36 Version 2.0 questionnaire, for thirty-eight patients who were followed for a minimum of two years. RESULTS: Fifty-two of the fifty-nine fractures healed. Six fractures had bone-grafting, and each progressed uneventfully to union. One patient required an amputation following a failed free tissue transfer. Two patients (3%) were deemed to have a deep wound infection and were successfully treated with a six-week course of culture-specific intravenous antibiotics. Three patients (5%) had a superficial wound infection that was successfully treated with oral antibiotics. The average physical component score on the Short Form-36 Version 2.0 was 40.3 points. The average mental component score (54.9 points) was better than the age-matched norm in the majority of the age groups. The average modified Mazur score was 44.8 of a possible 100, with most patients scoring in the poor range. CONCLUSIONS: Open reduction and internal fixation of open pilon fractures was accomplished with an acceptable outcome and a low prevalence of soft-tissue complications. We believe these results can be reproduced through routine use of an individualized treatment algorithm including the use of staged procedures, meticulous soft-tissue management, liberal use of temporizing external fixation, and a patient-specific approach to fixation and soft-tissue coverage.

Bioengineering of calvaria with adult stem cells.

BACKGROUND: Defects of the adult skull do not heal spontaneously, producing challenging problems for the craniofacial surgeon. Reconstruction of such defects requires either the placement of alloplastic material or the harvest of autogenous bone. A technique is described for the reconstruction of critical-sized, full-thickness calvarial defects in the adult rat model using specific adult stem cells, namely, multipotent adult stem cells. METHODS: The cells were harvested from adult skeletal muscle and cultured in an undifferentiated state within a matrix of polyglycolic acid mesh. An 8-mm critical-sized defect was created in the calvaria of adult rats and either left empty, filled with polyglycolic acid mesh alone, or filled with multipotent adult stem cells seeded into the polyglycolic acid mesh. After 12 weeks, the calvariae were harvested, stained, and blind graded by light microscopy on the presence or absence of reconstituted bone. RESULTS: A total of 22 animals were available for study: seven from the empty defect group, eight from the polymer group, and seven from the polymer plus stem cell group. The mean scores for the three groups were 1.9, 2.3, and 5.3, respectively. Statistical analysis showed statistical significance among the groups as a whole (p < 0.01) and between the polymer plus stem cell group and the empty defect and polymer-alone group. CONCLUSIONS: The results demonstrate that regeneration of calvarial bone is possible using stem cells harvested from adult skeletal muscle and seeded into a polyglycolic matrix. The technique may ultimately be used in clinical practice to reconstruct calvarial defects.

Stem cells isolated from adult rat muscle differentiate across all three dermal lineages.

Adult stem cells capable of differentiating into phenotypes from all three dermal layers were isolated from adult rat muscle. Stem cells were obtained by enzymatic digestion, followed by primary culture in Eagle's minimum essential medium +10% preselected horse serum. When the cells reached confluence, they were released by trypsin, filtered to remove differentiated myotubes, and then slow frozen in 7.5% dimethylsulfoxide to -80 degrees C. Thawed cells were the stem cells and were induced to differentiate with the nonspecific differentiating agent dexamethasone at concentrations of 10(-10)-10(-6) M. After a 6-week treatment with dexamethasone, the cells were assayed by immunohistochemistry for phenotypes of the mesodermal, ectodermal, and endodermal lineages. Examples of mesodermal phenotypes identified were as follows: bone, cartilage, and skeletal, smooth, and cardiac muscle. Ectodermal phenotypes identified were as follows: neurons and oligodendrocytes. Hepatocyte phenotypes identified represented the endodermal lineage. All the phenotypes were observed only with treatment with dexamethasone. However, nestin was observed in the absence of dexamethasone and may be a marker for uncommitted pluripotent stem cells. The results show that adult muscle contains pluripotent stem cells capable of differentiating across all three dermal lineages. Such cells could be used in the context of tissue engineering.

Effect of neurturin on multipotent cells isolated from the adult skeletal muscle.

Ligands of the glial cell line-derived neurotrophic factors (GDNF)-family are trophic factors for the development and survival of multiple cell types, however their effects on non-neuronal stem cells are unknown. We examined the action of neurturin on a candidate stem cell population isolated from adult skeletal muscles. When grown as spheres, these cells expressed mRNAs for GDNF, persephin, GFR-alpha2, GFR-alpha4 (neurturin receptor), and Ret. Exposure of these cells to neurturin significantly augmented cell numbers via increased cell proliferation. After addition of retinoic acid, the cells exited the cell cycle, developed thin processes, and became immunoreactive for betaIII-tubulin, while Ret mRNA expression decreased, without changes in the level of GFR-alpha2 mRNA. Neurturin induced an outgrowth of processes on these betaIII-tubulin positive cells. Neurturin may therefore be beneficial in the use of these multipotent cells isolated from adult muscles for autologous transplants in neurological applications.

Adult skeletal muscle stem cells differentiate into endothelial lineage and ameliorate renal dysfunction after acute ischemia.

We previously demonstrated that endothelial cells are severely damaged during renal ischemia-reperfusion and that transplantation of adult human endothelial cells into athymic nude rats subjected to renal ischemia resulted in a dramatic protection of the kidney against injury and dysfunction. Morphological studies demonstrated the engraftment of transplanted cells into renal microvasculature. The goal of the present study was to determine the potential efficacy of in vitro expanded skeletal muscle-derived stem cells (MDSC) differentiated along the endothelial lineage in ameliorating acute renal injury. MDSC obtained from the Tie-2-green fluorescent protein (GFP) mice were used as donors of differentiated and nondifferentiated stem cells. FVB mice, used as recipients, were subjected to renal ischemia and transplanted with the above MDSC. The differentiation of MDSC along the endothelial lineage was monitored by the appearance of Tie-2 promotor-driven expression of GFP. These mouse endothelial cell antigen-, endothelial nitric oxide synthase (eNOS)-, Flk-1-, Flt-1-, and CD31-positive cells engrafted into renal microvasculature and significantly protected short-term renal function after ischemia. Transplantation of nondifferentiated MDSC characterized by the expression of Sca-1 (low levels of CD34, Flk-1, and cKit, and negative for GFP, eNOS, and CD31) did not improve short-term renal dysfunction. In conclusion, the data 1) provide a rich source of MDSC, 2) delineate protocols for their in vitro expansion and differentiation along the endothelial lineage, and 3) demonstrate their efficacy in preserving renal function immediately after ischemic insult.

Isolation and characterization of cells with neurogenic potential from adult skeletal muscle.

Autologous cell therapies in neurodegenerative diseases and stroke will require an efficient generation of neuroprogenitors or neurons. We have previously shown that presumptive neural progenitors can be obtained from a candidate stem cell population isolated from adult skeletal muscle. Here we describe experimental conditions to isolate and characterize the cells with neurogenic potential from this population. Candidate stem cell population was isolated from adult skeletal muscle and expanded for selection during at least 30 cell divisions. FACS analysis revealed that this population was homogeneous with respect to CD45 (-), CD34 (-), and heterogeneous for CD90 (Thy-1) expression. The population was separated by cell sorting into three sub-populations based on CD90 expression (CD90-, CD90+, and CD90++) and each population expanded rapidly as free-floating spheres. When dissociated and plated in a neuronal differentiation medium, a large number of CD90+ cells acquired morphological characteristics of neuroprogenitors and neurons, and expressed markers of neurons but no markers of glial or muscle cells. In contrast, CD90- and CD90++ cells lacked this ability. Comparison of CD90+ and CD90- populations may be useful for studying the molecular characteristics defining the neuronal potential of stem cells from adult muscle. The selection of CD90+ expressing cells, combined with the growth conditions presented here, allows for rapid generation of a large number of cells which may be useful for autologous cell replacement therapies in the central nervous system.

Neuronal differentiation of stem cells isolated from adult muscle.

Lineage uncommitted pluripotent stem cells reside in the connective tissue of skeletal muscle. The present study was carried out with pluripotent stem cells (PPSCs) isolated from 6-month old rat muscle. Before differentiation, these cells were vimentin+, CD90+, CD45-, and varied in their expression of CD34. The PPSCs were expanded as non-adherent aggregates under similar conditions to those used to generate neurospheres from embryonic or neural stem cells. The PPSC-derived neurospheres were positive for nestin, an early marker present in neuronal precursors, and expressed the two alternative mRNA forms of the neuroectodermal marker Pax-6, as well as mRNA for Oct-4, a gene related to the pluripotentiality of stem cells. To confirm their neural potential, PPSC-derived neurospheres were plated on coated coverslips under varying conditions: Neurobasal medium with N2 or B27, and either NT3 or BDNF. After 4-6 days the cells expressed neuronal (Tuj1+, NF68), astrocytic (GFAP) and oligodendrocytic (MOSP+, MBP+) markers, both by immunocytochemistry and RT-PCR. In addition, PPSCs were cultured as monolayers under adherent conditions, exposed to growth factors and defined differentiating conditions for 5 hr, and subsequently kept for 2 days in a maturation medium. At this point they gave rise to a mixed population of early neural progenitors (Nestin+ or NG2+), immature and mature neurons (Tuj1+ and NF145+) and myelin producing oligodendrocytes (CNPase + and MOSP+). Our study shows that PPSCs present in adult muscle can overcome germ lineage restrictions and express the molecular characteristics of brain cells. Therefore, PPSCs isolated from adult muscle could provide a novel source for autologous cell replacement in neurodegenerative and demyelinating diseases.