In vitro and in vivo evaluation of heparin mediated growth factor release from tissue‐engineered constructs for anterior cruciate ligament reconstruction

Anterior cruciate ligament (ACL) rupture is a common injury often necessitating surgical treatment with graft reconstruction. Due to limitations associated with current graft options, there is interest in a tissue‐engineered substitute for use in ACL regeneration. While they represent an important step in translation to clinical practice, relatively few in vivo studies have been performed to evaluate tissue‐engineered ACL grafts. In the present study, we immobilized heparin onto electrospun polycaprolactone scaffolds as a means of incorporating basic fibroblast growth factor (bFGF) onto the scaffold. In vitro, we demonstrated that human foreskin fibroblasts (HFFs) cultured on bFGF‐coated scaffolds had significantly greater cell proliferation. In vivo, we implanted electrospun polycaprolactone grafts with and without bFGF into athymic rat knees. We analyzed the regenerated ACL using histological methods up to 16 weeks post‐implantation. Hematoxylin and eosin staining demonstrated infiltration of the grafts with cells, and picrosirius red staining demonstrated aligned collagen fibers. At 16 weeks postop, mechanical testing of the grafts demonstrated that the grafts had approximately 30% the maximum load to failure of the native ACL. However, there were no significant differences observed between the graft groups with or without heparin‐immobilized bFGF. While this study demonstrates the potential of a regenerative medicine approach to treatment of ACL rupture, it also demonstrates that in vitro results do not always predict what will occur in vivo. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:229–236, 2015.     

Esthesioneuroblastoma: An Update on the UCLA Experience, 2002–2013

Objectives To profile the clinical presentation and treatment results of esthesioneuroblastomas at the University of California, Los Angeles (UCLA), from 2002 to 2013. Design Retrospective review. Setting Tertiary academic institution. Participants Forty-one patients with esthesioneuroblastomas treated at UCLA. Main Outcome Measures Overall survival (OS) and recurrence-free survival (RFS). Results Thirty-six patients were included with a mean age of 50.1 years and a median duration of follow-up of 33 months. The 5-year RFS and OS were 54% and 82%, respectively. Modified Kadish stage was the only factor identified to affect OS. Multivariate analysis demonstrated that tumor grade was the only factor that had an independent impact on RFS. There was no statistical difference in survival among the surgical approaches chosen. Conclusions The updated data on the UCLA experience reveals that all three surgical approaches chosen provide comparable survival, although longer follow-up will be needed to ascertain if these findings hold true. The endoscopic approach had a statistically significant decrease in length of hospital stay and a trend toward reduced blood loss, intensive care unit admission, and complications. The modified Kadish staging was the only factor identified to predict OS. Multivariate analysis revealed that tumor grade was an independent predictor of recurrence; therefore, its importance should be emphasized in future staging systems.     

Follicle stimulating hormone receptor protein is expressed in ovine uterus during the estrous cycle and utero-placenta during early pregnancy: An immunohistochemical study

Follicle stimulating hormone (FSH) is a well characterized gonadotropin that controls primarily development and functions of ovarian follicles in mammalian species. FSH binds to a specific G protein-coupled receptor (FSHR) belonging to the glycoprotein hormone receptor family that plays an essential role in reproduction. Although the primary location of FSHR is in the gonads (mainly in ovarian follicles), FSHR protein and/or mRNA have also been detected in extragonadal female reproductive tissues including embryo, placenta, endometrium, cervix, ovarian cancer tissues, and/or endometriotic lesions in several species. To determine the pattern of FSHR expression in the uterus and placenta, uterine tissues were collected at the early, mid- and/or late luteal phases of the estrous cycle from non-treated or FSH-treated ewes, and utero-placental tissues were collected during early pregnancy followed by immunohistochemistry and image generation. FSHR was immunolocalized to several uterine and utero-placental compartments including luminal epithelium, endometrial glands and surrounding stroma, myometrium, and endothelium and vascular smooth muscle cells in endometrium, myometrium and mesometrium. Intensity of staining and distribution of FSHR in selected compartments differed and seems to depend on the stage of the estrous cycle or pregnancy, and FSH-treatment. These novel data demonstrate differential expression of FSHR protein indicating that FSH plays a specific role in regulation of uterine and utero-placenta functions in sheep.     

Carotid Atherosclerosis Is Associated With Poorer Hearing in Older Adults

ObjectivesCardiovascular disease may be linked to hearing loss through narrowing of the nutrient arteries of the cochlea, but large-scale population-based evidence for this association remains scarce. We investigated the association of carotid atherosclerosis as a marker of generalized cardiovascular disease with hearing loss in a population-based cohort.DesignCross-sectional.SettingA population-based cohort study.Participants3724 participants [mean age: 65.5 years, standard deviation (SD): 7.5, 55.4% female].MethodsUltrasound and pure-tone audiograms to assess carotid atherosclerosis and hearing loss.ResultsWe investigated associations of carotid plaque burden and carotid intima-media thickness (IMT) (overall and side-specific carotid atherosclerosis) with hearing loss (in the best hearing ear and side-specific hearing loss) using multivariable linear and ordinal regression models. We found that higher maximum IMT was related to poorer hearing in the best hearing ear [difference in decibel hearing level per 1-mm increase in IMT: 2.09 dB, 95% confidence interval (CI): 0.08, 4.10]. Additionally, third and fourth quartile plaque burden as compared to first quartile was related to poorer hearing in the best hearing ear (difference: 1.06 dB, 95% CI: 0.04, 2.08; and difference: 1.55 dB, 95% CI: 0.49, 2.60, respectively). Larger IMT (difference: 2.97 dB, 95% CI: 0.79, 5.14), third quartile plaque burden compared to first quartile (difference: 1.24 dB, 95% CI: 0.14, 2.35), and fourth plaque quartile compared to first quartile (difference: 2.12 dB, 95% CI: 0.98, 3.26) in the right carotid were associated with poorer hearing in the right ear.Conclusions and ImplicationsCarotid atherosclerosis is associated with poorer hearing in older adults, almost exclusively with poorer hearing in the right ear. Based on our results, it seems that current therapies for the prevention of cardiovascular disease may also prove beneficial for hearing loss in older adults by promoting and maintaining inner ear health.     

Dexamethasone loaded multi-layer poly-l-lactic acid/pluronic P123 composite electrospun nanofiber scaffolds for bone tissue engineering and drug delivery

In tissue engineering, it is common to mix drugs that can control proliferation and differentiation of cells into polymeric solutions as part of composite to get bioactive scaffolds. However, direct incorporation of drugs might potentially result in undesired burst release. To overcome this problem, here we developed electrospun multilayer drug loaded poly-l-lactic acid/pluronic P123 (PLLA–P123) composite scaffolds. The drug was loaded into the middle layer. The surface, the mechanical and physiochemical properties of the scaffolds were evaluated. The drug release profiles were monitored. Finally, the osteogenic proliferation and differentiation potential were determined. The scaffolds fabricated here have appropriate surface properties, but with different mechanical strength and osteogenic proliferation and differentiation. Multi-layer scaffolds where the drug was in the middle layer and PLLA-plasma and PLLA–P123 with cover layer showed the best osteogenic proliferation and differentiation than the other groups of scaffolds. The drug release profiles of the scaffolds were completely different: single layer scaffolds showed burst release within the first day, while multilayer scaffolds showed controlled release. Therefore, the multilayer drug loaded scaffolds prepared have dual benefits can provide both better osteogenesis and controlled release of drugs and bioactive molecules at the implant site.     

Subacute ascending numbness

A 21-year-old male presented with two weeks of ascending numbness involving all 4 limbs, and imbalance when walking. Examination revealed diminished vibration and proprioception at the fingers, toes, and ankles, a high steppage gait and a positive Romberg sign. He had no weakness in any muscle groups. Laboratory data included vitamin B12 218 pg/mL (normal range: 200–800 pg/mL), homocysteine 87 μmol/L (normal range: 2.2–13.2 μmol/L), and non-reactive RPR. Magnetic resonance imaging of the cervical spine revealed abnormal T2-weighted hyperintensity along the posterior columns extending from C2 to C7.