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MINI: This study compared clinical and patient-reported outcomes following transforaminal lumbar interbody fusion between patients who use or do not use marijuana. We found that patients who use marijuana are younger, but do not demonstrate any differences in preoperative or postoperative Oswestry disability index scores or rates of fusion.A retrospective cohort study.The purpose of this study was to evaluate marijuana usage and its effect on outcomes following transforaminal lumbar interbody fusion (TLIF).As marijuana becomes legalized throughout the United States, its medicinal and recreational usage is becoming more mainstream. Clinicians currently have little guidance regarding both short-term and long-term effects of marijuana usage on surgical interventions. While the rate of lumbar spinal fusion in the United States continues to grow, the effect of marijuana usage on fusion remains uncertain.One hundred two patients who underwent TLIF performed by the same surgeon were followed for 12 months. Patients were self-reported for marijuana usage (n = 36). Patient reported outcome measures included preoperative Oswestry disability index (ODI), 6-month ODI, and 12-month ODI, as well as length of stay (LOS), complications, return to operating room (OR), revision surgery, and confirmed fusion. Continuous variables were compared using the independent two-sample t test or analysis of variance (ANOVA), whereas categorical variables were analyzed using the chi-square or Fischer exact tests. Adjusted analysis was performed using a multivariate logistic regression model.Marijuana usage was associated with a younger population (P 0.001), but showed no difference regarding sex or body mass index compared with the non-usage group. There was no statistically significant difference in complications, return to OR, or revision surgery between groups. When controlling for factors such as age and preoperative ODI, multivariate analysis demonstrated that marijuana usage did not limit postoperative ODI reduction. The marijuana usage group demonstrated shorter LOS (2.42 vs. 3.00 d, P = 0.020). Fusion rates at 12 months were similar between groups (96% vs. 92.3%, P = 0.678). ODI was similar between groups at all time points.Perioperative outcomes were similar in patients who underwent TLIF regardless of marijuana usage.3.A retrospective cohort study. The purpose of this study was to evaluate marijuana usage and its effect on outcomes following transforaminal lumbar interbody fusion (TLIF). As marijuana becomes legalized throughout the United States, its medicinal and recreational usage is becoming more mainstream. Clinicians currently have little guidance regarding both short-term and long-term effects of marijuana usage on surgical interventions. While the rate of lumbar spinal fusion in the United States continues to grow, the effect of marijuana usage on fusion remains uncertain. One hundred two patients who underwent TLIF performed by the same surgeon were followed for 12 months. Patients were self-reported for marijuana usage (n = 36). Patient reported outcome measures included preoperative Oswestry disability index (ODI), 6-month ODI, and 12-month ODI, as well as length of stay (LOS), complications, return to operating room (OR), revision surgery, and confirmed fusion. Continuous variables were compared using the independent two-sample t test or analysis of variance (ANOVA), whereas categorical variables were analyzed using the chi-square or Fischer exact tests. Adjusted analysis was performed using a multivariate logistic regression model. Marijuana usage was associated with a younger population (P 0.001), but showed no difference regarding sex or body mass index compared with the non-usage group. There was no statistically significant difference in complications, return to OR, or revision surgery between groups. When controlling for factors such as age and preoperative ODI, multivariate analysis demonstrated that marijuana usage did not limit postoperative ODI reduction. The marijuana usage group demonstrated shorter LOS (2.42 vs. 3.00 d, P = 0.020). Fusion rates at 12 months were similar between groups (96% vs. 92.3%, P = 0.678). ODI was similar between groups at all time points. Perioperative outcomes were similar in patients who underwent TLIF regardless of marijuana usage. Level of Evidence: 3.

Study Design:Retrospective cohort study.Objectives:The objective of this study was to determine whether lower socioeconomic status was associated with increased resource utilization following anterior discectomy and fusion (ACDF).Methods:The National Inpatient Sample database was queried for patients who underwent a primary, 1- to 2-level ACDF between 2005 and 2014. Trauma, malignancy, infection, and revision surgery were excluded. The top and bottom income quartiles were compared. Demographics, medical comorbidities, length of stay, complications, and hospital cost were compared between patients of top and bottom income quartiles.Results:A total of 69 844 cases were included. The bottom income quartile had a similar mean hospital stay (2.04 vs 1.77 days, P = .412), more complications (2.45% vs 1.77%, P < .001), and a higher mortality rate (0.18% vs 0.11%, P = .016). Multivariate analysis revealed bottom income quartile was an independent risk factor for complications (odds ratio = 1.135, confidence interval = 1.02-1.26). Interestingly, the bottom income quartile experienced lower mean hospital costs ($17 041 vs $17 958, P < .001).Conclusion:Patients in the lowest income group experienced more complications even after adjusting for comorbidities. Therefore, risk adjustment models, including socioeconomic status, may be necessary to avoid potential problems with access to orthopedic spine care for this patient population.

Study Design: Retrospective, database study. Objectives: The aim of this study was to investigate incidence and risk factors associated with venous thromboembolic events (VTEs) after lumbar spine surgery. Methods: Patients who underwent lumbar surgery between 2007 and 2014 were identified using the Humana within PearlDiver database. ICD-9 (International Classification of Diseases Ninth Revision) diagnosis codes were used to search for the incidence of VTEs among surgery types, patient demographics and comorbidities. Complications including DVT and PE were queried each day from the day of surgery to postoperative day 7 and for periods 0 to 1 week, 0 to 1 month, 0 to 2 months, and 0 to 3 months postoperatively. Results: A total of 64 892 patients within the Humana insurance database received lumbar surgery between 2007 and 2014. Overall VTE rate was 0.9% at 1 week, 1.8% at 1 month, and 2.6% at 3 months postoperatively. Among patients that developed a VTE within 1 week postoperatively, 45.3% had a VTE on the day of surgery. Patients with 1 or more identified risk factors had a VTE incidence of 2.73%, compared with 0.95% for patients without risk factors ( P < .001). Risk factors associated with the highest VTE incidence and odds ratios (ORs) were primary coagulation disorder (10.01%, OR 4.33), extremity paralysis (7.49%, OR 2.96), central venous line (6.70%, OR 2.87), and varicose veins (6.51%, OR 2.58). Conclusions: This study identified several patient comorbidities that were independent predictors of postoperative VTE occurrence after lumbar surgery. Clinical VTE risk assessment may improve with increased focus toward patient comorbidities rather than surgery type or patient demographics.

Study DesignRetrospective analysis of a nationwide private insurance database. Chi-square analysis and linear regression models were utilized for outcome measures.PurposeThe purpose of this study was to investigate any relationship between lumbar degenerative disc disease, diabetes, obesity and smoking tobacco.Overview of LiteratureDiabetes, obesity, and smoking tobacco are comorbid conditions known to individually have effect on degenerative disc disease. Most studies have only been on a small populous scale. No study has yet to investigate the combination of these conditions within a large patient cohort nor have they reviewed the combination of these conditions on degenerative disc disease.MethodsA retrospective analysis of insurance billing codes within the nationwide Humana insurance database was performed, using PearlDiver software (PearlDiver, Inc., Fort Wayne, IN, USA), to identify trends among patients diagnosed with lumbar disc degenerative disease with and without the associated comorbidities of obesity, diabetes, and/or smoking tobacco. Patients billed for a comorbidity diagnosis on the same patient record as the lumbar disc degenerative disease diagnosis were compared over time to patients billed for lumbar disc degenerative disease without a comorbidity. There were no sources of funding for this manuscript and no conflicts of interest.ResultsThe total number and prevalence of patients (per 10,000) within the database diagnosed with lumbar disc degenerative disease increased by 241.4% and 130.3%, respectively. The subsets of patients within this population who were concurrently diagnosed with either obesity, diabetes, tobacco use, or a combination thereof, was significantly higher than patients diagnosed with lumbar disc degenerative disease alone (p p p ConclusionsDiabetes, obesity and cigarette smoking each are significantly associated with an increased diagnosis of lumbar degenerative disc disease. The combination of smoking and obesity had a synergistic effect on increased rates of lumbar degenerative disc disease. Patient education and preventative care is a vital goal in prevention of degenerative disc disease within the general population.

The spine has several important functions including load transmission, permission of limited motion, and protection of the spinal cord. The vertebrae form functional spinal units, which represent the smallest segment that has characteristics of the entire spinal column. Discs and paired facet joints within each functional unit form a three-joint complex between which loads are transmitted. Surrounding the spinal motion segment are ligaments, composed of elastin and collagen, and joint capsules which restrict motion to within normal limits. Ligaments have variable strengths and act via different lever arm lengths to contribute to spinal stability. As a consequence of the longer moment arm from the spinous process to the instantaneous axis of rotation, inherently weaker ligaments (interspinous and supraspinous) are able to provide resistance to excessive flexion. Degenerative processes of the spine are a normal result of aging and occur on a spectrum. During the second decade of life, the intervertebral disc demonstrates histologic evidence of nucleus pulposus degradation caused by reduced end plate blood supply. As disc height decreases, the functional unit is capable of an increased range of axial rotation which subjects the posterior facet capsules to greater mechanical loads. A concurrent change in load transmission across the end plates and translation of the instantaneous axis of rotation further increase the degenerative processes at adjacent structures. The behavior of the functional unit is impacted by these processes and is reflected by changes in the stress-strain relationship. Back pain and other clinical symptoms may occur as a result of the biomechanical alterations of degeneration.

Percutaneous sacroiliac (SI) screw fixation is indicated for unstable posterior pelvic ring injuries, sacral fractures, and SI joint dislocations. This article provides a review of indications and contraindications, preoperative planning, imaging techniques and relevant anatomy, surgical technique, complications and their management, and outcomes after SI screw insertion.

Background context Spinal gunshot injuries (spinal GSIs) are a major cause of morbidity and mortality in both military and civilian populations. These injuries are likely to be encountered by spine care professionals in many treatment settings. A paucity of resources is available to summarize current knowledge of spinal GSI evaluation and management. Purpose The aim was to summarize the ballistics, epidemiology, evaluation, treatment, and outcomes of spinal GSI among civilian and military populations. Study design This was a review of the current literature reporting spinal GSI management. Methods MEDLINE (PubMed) was queried for recent studies and case reports of spinal GSI evaluation and management. Results Spinal GSI now comprise the third most common cause of spinal injury. Firearms that produce spinal GSI can be divided into categories of high- and low-energy depending on the initial velocity of the projectile. Neural and mechanical spinal damage varies with these types and results from several factors including direct impact, concussion waves, tissue cavitation, and thermal energy. Management of spinal GSI also depends on several factors including neurologic function and change over time, spinal stability, missile tract through the body, and concomitant injury. Surgical treatment is typically indicated for progressive neurologic changes, spinal instability, persistent cerebrospinal fluid leak, and infection. Surgical treatment for GSI affecting T12 and caudal often has a better outcome than for those cranial to T12. Surgical exploration and removal of missile fragments in the spinal canal are typically indicated for incomplete or worsening neurologic injury. Conclusions Treatment of spinal GSI requires a multidisciplinary approach with the goal of maintaining or restoring spinal stability and neurologic function and minimizing complications. Concomitant injuries and complications after spinal GSI can present immediate and ongoing challenges to the medical, surgical and rehabilitative care of the patient.

Medical education reform is underway, but the optimal course for change has yet to be seen. While planning for the redesign of a renal physiology course at the Duke School of Medicine, the authors used a Q-sort survey to assess students' attitudes and learning preferences to inform curricular change. The authors invited first-year medical students at the Duke School of Medicine to take a Q-sort survey on the first day of renal physiology. Students prioritized statements related to their understanding of renal physiology, learning preferences, preferred course characteristics, perceived clinical relevance of renal physiology, and interest in nephrology as a career. By-person factor analysis was performed using the centroid method. Three dominant factors were strongly defined by learning preferences: “readers” prefer using notes, a textbook, and avoid lectures; “social-auditory learners” prefer attending lectures, interactivity, and working with peers; and “visual learners” prefer studying images, diagrams, and viewing materials online. A smaller, fourth factor represented a small group of students with a strong predisposition against renal physiology and nephrology. In conclusion, the Q-sort survey identified and then described in detail the dominant viewpoints of our students. Learning style preferences better classified first-year students rather than any of the other domains. A more individualized curriculum would simultaneously cater to the different types of learners in the classroom.

Adult spinal deformity is a common disorder with an increasing clinical and societal impact based on the aging demographic throughout the world. Adult spinal deformity in the adult population has a significant and measurable impact on health-related quality of life. A significant proportion of this affected populace will require treatment in some form or another. In general, the first-line of treatment is non-operative, but a subset will require operative intervention. Once surgical intervention is chosen, there are numerous methods that may provide surgeons with adequate tools for successful outcomes. The purpose of this review article is to discuss the importance of adult deformity in the spectrum of disorders that affect the spine, to define specific considerations that are useful in guiding an evidence-based approach to care, and to elaborate on the variety of surgical techniques for which to address the issue of spinal deformity.

Spinal fusion with or without instrumentation often requires the use of bone graft. Bone graft may be autogenous or exogenous. There are various forms of bone graft which may be acquired from numerous sites. Knowledge of fusion biology is imperative for understanding the benefits and limitations of these grafts. Equally as important is the knowledge of outcome measures, management of donor-site morbidity, and potential reconstruction. This review details the methods of obtaining bone graft and details the properties of each, as well as discusses observed outcomes, donor-site morbidities, and reconstruction techniques.

AOSpine masters series. , AOSpine masters series. , کتابخانه مرکزی دانشگاه علوم پزشکی تهران

Bone grafting materials are the core element of spine fusion, providing the environment for solid bone formation between two vertebrae. Ideal bone graft is osteoconductive, osteoinductive, and osteogenic. All grafting materials can be divided into three main groups: autologous, allograft, and graft substitutes (extenders, enhancers, or substitutes). Autogenous iliac crest bone graft is the only graft that possesses all components needed for bone formation. However, autogenous bone grafts are often limited in quantity and its harvest is associated with complications. Allograft bone is obtained from cadaver tissues and has osteoconductive and minimal osteoinductive properties. It comes in various shapes and forms with the main disadvantages being mechanical properties and potential for disease transmission. Bone substitutes include demineralized bone matrix (DBM), ceramics, osteoinductive proteins, autologous platelet concentrate, and bone marrow aspirates. The right choice of bone strongly depends on the patient’s risk factors, type of fusion, and number of levels.

Spine surgery training in the United States currently involves residency training in neurological or orthopaedic surgery. Because of different core residency surgical requirements, the volume of spine surgery procedures may vary between the 2 residencies.We reviewed the Accreditation Council for Graduate Medical Education resident case logs for both orthopaedic surgery and neurological surgery for exposure to spine surgery procedures for the graduating years of 2009 to 2018.The average number of spine surgery procedures performed during that 10-year period was 433.8 for neurosurgery residents and 119.5 for orthopaedic surgery residents (p0.01). From 2009 to 2018, neurosurgery residents saw an increase of 26.5% in spine surgery procedures (from 389.6 to 492.9 procedures), whereas orthopaedic surgery residents saw a decrease of 41.3% (from 141.1 to 82.8 procedures). The 10-year average percentage of total spine procedures among all total surgical cases was 33.5% for neurosurgery residents compared with 6.2% for orthopaedic surgery residents (p0.01). This percentage decreased for both neurosurgery residents (35.8% in 2009 to 31.3% in 2018) and orthopaedic surgery residents (7.2% in 2009 to 4.9% in 2018). Neurosurgical residents performed 3.6 times more total spine procedures than orthopaedic surgery residents on average, a number that increased from 2.8-fold in 2009 to 6.0-fold in 2018.The case volume of spine surgery procedures varies greatly, with higher rates for neurological surgery and lower rates for orthopaedic surgery residencies, with an increasing discrepancy over time. Although case volume alone cannot solely determine quality of training, it is one measure to assess opportunities to develop optimal spine education around a certain accepted volume of surgical patient care. Not accounted for here are additional postgraduate spine cases performed by orthopaedic surgery residents who pursue spine fellowship training (an additional 300 to 500 cases). The results described herein may help to explore the various needs of and differences between residents seeking to pursue careers in spine as well as the role of spine surgery fellowships currently and in the future.

Obtaining an orthopaedic surgery residency is competitive. Advisors must understand what factors may help unmatched candidates reapply successfully.We determined (1) the attitude of leaders of orthopaedic surgery residency programs toward interviewing unmatched students; (2) whether a surgical internship or a research year is preferred in considering reapplicants; (3) the importance of United States Medical Licensing Examination (USMLE) scores, recommendations, and Alpha Omega Alpha (AOA) membership; and (4) whether academic and nonacademic programs evaluate reapplicants differently.We sent an anonymous 19-question survey to 151 Accreditation Council for Graduate Medical Education (ACGME)-accredited orthopaedic surgery residency programs in five waves, 1 week apart (December 5, 2009-January 5, 2010). Investigators were blinded to the respondents' identities.Ninety-one of the 151 programs (60%) responded. Sixty-eight of the 91 programs (75%) stated they rarely accept unmatched applicants. Sixty-eight programs (75%) agreed an unmatched applicant should do a surgery internship for 1 year. Of the 36 programs that recommended a research year, 32 were academic programs. Academic programs were more likely than nonacademic programs to view as important new recommendations (85% versus 67%), minimum scores of 220 on Step I (67% versus 49%) and Step II (64% versus 36%), and AOA membership (85% versus 67%).By completing a surgical internship, unmatched students may increase their chances of matching. Students considering academic programs should ensure their academic record meets certain benchmarks and may consider a research year but risk limiting their acceptance to academic programs.

There has been a conscious effort to address osteoporosis in the aging population. As bisphosphonate and intermittent parathyroid hormone (PTH) therapy become more widely prescribed to treat osteoporosis, it is important to understand their effects on other physiologic processes, particularly the impact on spinal fusion. Despite early animal model studies and more recent clinical studies, the impact of these medications on spinal fusion is not fully understood. Previous animal studies suggest that bisphosphonate therapy resulted in inhibition of fusion mass with impeded maturity and an unknown effect on biomechanical strength. Prior animal studies demonstrate an improved fusion rate and fusion mass microstructure with the use of intermittent PTH. The purpose of this study was to determine if bisphosphonates and intermittent PTH treatment have impact on human spinal fusion. A systematic review of the literature published between 1980 and 2015 was conducted using major electronic databases. Studies reporting outcomes of human subjects undergoing 1, 2, or 3-level spinal fusion while receiving bisphosphonates and/or intermittent PTH treatment were included. The results of relevant human studies were analyzed for consensus on the effects of these medications in regards to spinal fusion. There were nine human studies evaluating the impact of these medications on spinal fusion. Improved fusion rates were noted in patients receiving bisphosphonates compared to control groups, and greater fusion rates in patients receiving PTH compared to control groups. Prior studies involving animal models found an improved fusion rate and fusion mass microstructure with the use of intermittent PTH. No significant complications were demonstrated in any study included in the analysis. Bisphosphonate use in humans may not be a deterrent to spinal fusion. Intermittent parathyroid use has shown early promise to increase fusion mass in both animal and human studies but further studies are needed to support routine use.

Watertight dural repair is crucial for both incidental durotomy and closure after intradural surgery.The study aimed to describe a perfusion-based cadaveric simulation model with cerebrospinal fluid (CSF) reconstitution and to compare spine dural repair techniques.The study is set in a fresh tissue dissection laboratory.The sample includes eight fresh human cadavers.A watertight closure was achieved when pressurized saline up to 40 mm Hg did not cause further CSF leakage beyond the suture lines.Fresh human cadaveric specimens underwent cannulation of the intradural cervical spine for intrathecal reconstitution of the CSF system. The cervicothoracic dura was then exposed from C7-T12 via laminectomy. The entire dura was then opened in six cadavers (ALLSPINE) and closed with 6-0 Prolene (n=3) or 4-0 Nurolon (n=3), and pressurized with saline via a perfusion system to 60 mm Hg to check for leakage. In two cadavers (INCISION), six separate 2-cm incisions were made and closed with either 6-0 Prolene or 4-0 Nurolon, and then pressurized. A hydrogel sealant was then added and the closure was pressurized again to check for further leakage.Spinal laminectomy with repair of intentional durotomy was successfully performed in eight cadavers. The operative microscope was used in all cases, and the model provided a realistic experience of spinal durotomy repair. For ALLSPINE cadavers (mean: 240 mm dura/cadaver repaired), the mean pressure threshold for CSF leakage was observed at 66.7 (±2.9) mm Hg in the 6-0 Prolene group and at 43.3 (±14.4) mm Hg in the 4-0 Nurolon group (p.05). For INCISION cadavers, the mean pressure threshold for CSF leakage without hydrogel sealant was significantly higher in 6-0 Prolene group than in the 4-0 Nurolon group (6-0 Prolene: 80.0±4.5 mm Hg vs. 4-0 Nurolon: 32.5±2.7 mm Hg; p.01). The mean pressure threshold for CSF leakage with the hydrogel sealants was not significantly different (6-0 Prolene: 100.0±0.0 mm Hg vs. 4-0 Nurolon: 70.0±33.1 mm Hg). The use of a hydrogel sealant significantly increased the pressure thresholds for possible CSF leakage in both the 6-0 Prolene group (p=.01) and the 4-0 Nurolon group (p.01) when compared with mean pressures without the hydrogel sealant.We described the feasibility of using a novel cadaveric model for both the study and training of watertight dural closure techniques. 6-0 Prolene was observed to be superior to 4-0 Nurolon for watertight dural closure without a hydrogel sealant. The use of a hydrogel sealant significantly improved watertight dural closures for both 6-0 Prolene and 4-0 Nurolon groups in the cadaveric model.

Study design Retrospective analysis of national insurance billing database. Objective To examine trends in reoperation after single-level lumbar discectomy. Summary of background data Lumbar discectomy is the most commonly performed procedure for treatment of radiculopathy caused by disc herniation. Randomized clinical trials have demonstrated the advantage of discectomy over nonsurgical treatment options, allowing for a more rapid reduction in symptoms. However, population-level data regarding reoperation after single level discectomy is limited. Methods Data were collected using the commercially available PearlDiver software for patients billed with the Current Procedural Terminology code for our index procedure, hemilaminotomy and removal of disc material, between January 2007 and September 2014. The index group was then followed for up to 4 years for recurrent lumbar surgery, including spinal fusion, laminectomy, and additional discectomy. Results Analysis of data obtained from 13,654 patient records revealed a rate of additional lumbar surgeries after single-level discectomy of 3.95% (539/13654) within 3 months and 12.2% (766/6274) within 4 years of the index procedure. Lumbar spinal fusion was performed on 5.9% (370/6274) of patients within 4 years. Patients who received a re-exploration discectomy within 2 years of the index procedure went on to receive lumbar fusion at a rate of 38.4% (48/125) within the 4 years after the re-exploration discectomy. The average additional cost of lumbar reoperation, as measured by insurance reimbursement, was approximately $11,161 per-patient per year. Conclusion We report an overall 4-year reoperation rate of 12.2% after single-level discectomy. In addition, we report a rate of progression to lumbar fusion following re-exploration discectomy of 38.4% within 4 years of reoperation. Further studies are needed regarding the best treatment algorithm in patients with reherniation or iatrogenic instability after lumbar discectomy. This study should enhance the shared decision making process by providing surgeons and patients with valuable data regarding the frequency and nature of reoperations after discectomy. Level of evidence 3.

Lumbar interbody fusion is an important technique for the treatment of degenerative disc disease and degenerative scoliosis. The oblique lumbar interbody fusion (OLIF) establishes a minimally invasive retroperitoneal exposure anterior to the psoas and lumbar plexus. In this video case presentation, the authors demonstrate the techniques of the OLIF at L5–S1 performed on a 69-year-old female with degenerative scoliosis as one component of an overall strategy for her deformity correction.The video can be found here: https://youtu.be/VMUYWKLAl0g.

Proximal junctional kyphosis is an increasingly recognized complication following long-segment posterior spinal fusion for adult spinal deformity. The authors describe a novel technique for interspinous ligament reinforcement at the proximal adjacent levels using a cadaveric semitendinosus tendon graft secured with an Ethibond No. 2 double filament (Ethicon, Somerville, New Jersey) via the Krackow suture weave. A retrospective review identified 4 patients who had received this graft. No proximal junctional kyphosis was seen at a mean short-term follow-up of 5.5 months. Interspinous ligament reinforcement at the proximal adjacent level with a cadaveric semitendinosus tendon graft is a feasible strategy for preventing proximal junctional kyphosis. [ Orthopedics. 2017; 40(1):e206–e210.]

The Dynesys dynamic stabilization system is an alternative to rigid instrumentation and fusion for the treatment of lumbar degenerative disease. Although many outcomes studies have shown good results, currently lacking is a comprehensive report on complications associated with this system, especially in terms of how it compares with reported complication rates of fusion. For the present study, the authors reviewed the literature to find all studies involving the Dynesys dynamic stabilization system that reported complications or adverse events. Twenty-one studies were included for a total of 1166 patients with a mean age of 55.5 years (range 39–71 years) and a mean follow-up period of 33.7 months (range 12.0–81.6 months). Analysis of these studies demonstrated a surgical-site infection rate of 4.3%, pedicle screw loosening rate of 11.7%, pedicle screw fracture rate of 1.6%, and adjacent-segment disease (ASD) rate of 7.0%. Of studies reporting revision surgeries, 11.3% of patients underwent a reoperation. Of patients who developed ASD, 40.6% underwent a reoperation for treatment. The Dynesys dynamic stabilization system appears to have a fairly similar complication-rate profile compared with published literature on lumbar fusion, and is associated with a slightly lower incidence of ASD.

Tibial tubercle avulsion fractures most commonly occur in adolescent boys and usually result from pushing off or landing while jumping. These fractures are relatively uncommon but can have a significant functional effect. The purpose of this study was to determine the long-term outcome with return to play in 8 adolescent basketball players with at least 4 years of postoperative reconditioning. Results with return to play at the preinjury level are favorable after treatment of acute tibial avulsion fractures in adolescent basketball players. Long-term outcome was excellent in all patients regardless of fracture type. Open reduction and internal fixation using 1 or 2 cancellous bone screws achieved union in all cases.

BACKGROUND:: This study summarizes orthopedic injuries sustained in motorcycle collisions in patients presenting to a Level I trauma center. METHODS:: We performed a retrospective review of orthopedic injuries in motorcycle trauma victims brought into the emergency department. Of 2,634 presenting cases, 151 were identified as involving motorcycle collisions. Variables included age, gender, mechanism of injury, type and location of injury, concomitant injuries, length of hospitalization, number of orthopedic procedures during primary admission, and subsequent readmission. RESULTS:: A total of 71.5% of patients required orthopedic consultation. Average age was 35.0 years, with men injured at a ratio of 8:1. The most common mechanism of injury was motorcycle versus automobile (n = 48). A total of 206 fractures in 108 patients were discovered. The most common site of fracture involved the lower extremities. Open reduction with internal fixation was performed on 110 fractures (69 patients) during primary admission. Fifty-seven patients (52.8%) sustained open fractures requiring emergent orthopedic intervention. Fifty-three patients had various concomitant complications. Two patients died during initial hospitalization. Average hospitalization for patients without orthopedic consultation was 11.9 days versus 13.8 days with orthopedic consultation. The average number of orthopedic procedures performed on patients was 1.6. CONCLUSIONS:: Motorcycle collisions frequently involve patients in their working prime, thus placing substantial burden on the individual and society. Although these patients must continue to receive Level I trauma care, strengthened prevention and improved education efforts are warranted. Language: en

Background Most surgeons performing total ankle arthroplasty (TAA) suggest that accurate tibial preparation perpendicular to the tibial shaft axis improves outcomes. Recent studies demonstrate that computerized surgical navigation significantly improves the accuracy of tibial preparation in total knee arthroplasty (TKA). Methods We performed the tibial preparation for TAA in seven matched pairs of cadaver lower extremities. One set of matched pairs was prepared using the conventional external tibial alignment guide/cutting block from the Scandanavian Total Ankle Replacement system (STAR, Waldemar Link GmbH & Co., Hamburg, Germany) under fluoroscopic guidance. The second set of matched pairs was prepared using the VectorVision® navigation system (BrainLAB, Munich, Germany), with currently available computed tomography (CT)-based TKA software. Pre-operative CT data were used to assess the tibial mechanical axis. In both groups, accuracy of the tibial plafond preparation relative to the tibial shaft axis in both the coronal and sagittal planes was determined by fluoroscopic, radiographic and CT analysis. Results Mean values of the tibial cut for the set of matched-pair tibiae prepared by the conventional surgical method ranged across the three imaging assessment techniques in the ranges 89.3–89.6° (coronal plane, anteroposterior) and 90.3–90.4° (sagittal plane, lateral). For the computer-navigated set, the values were 89.7–89.9° (coronal) and 89.1–89.4° (sagittal). Comparison between the conventional and computer-navigated tibial measurements were not different at the 95% confidence interval (CI) for CT, fluoroscopy or radiographic assessments. Conclusions Our results demonstrate that accuracy of TAA tibial preparation using computer-navigation equals that of the conventional technique performed by a foot and ankle surgeon experienced in TAA. We anticipate that this investigation will encourage the development of computer-navigation applications specific to TAA, with the potential of improving accuracy over conventional methods. Copyright © 2008 John Wiley & Sons, Ltd.

ObjectivesFifty percent of human aortocoronary saphenous vein grafts are occluded after 10 years. Intimal hyperplasia is an initial step in graft occlusion and consists of vascular smooth muscle cell proliferation. Phosphatidylinositol 3-kinase and its downstream regulator, the inositol 3-phosphatase PTEN (phosphatase and tensin homolog deleted on chromosome 10), are important regulators of vascular smooth muscle cell proliferation, migration, and cell death. This study tests whether overexpression of PTEN in aortocoronary saphenous vein grafts can reduce intimal hyperplasia.MethodsAdult dogs underwent aortocoronary bypass grafting to the left anterior descending artery by using the autologous saphenous vein. Saphenous vein grafts were treated with phosphate-buffered saline (n = 9), empty adenovirus (n = 8), or adenovirus encoding for PTEN (n = 8). Arteriography at 30 and 90 days assessed saphenous vein graft patency. A subset received saphenous vein grafts treated with a marker transgene (β-galactosidase, n = 3), empty adenovirus (n = 4), or adenovirus encoding for PTEN (n = 4) and were killed on postoperative day 3 to confirm expression. Vascular smooth muscle cells were isolated from canine saphenous vein infected with adenovirus encoding for PTEN, and immunoblotting and proliferation assays were performed.ResultsSaphenous vein graft transgene expression was confirmed by means of immunohistochemistry, immunoblotting, and polymerase chain reaction. Arteriograms revealed all saphenous vein grafts to be patent. Saphenous vein grafts treated with adenovirus encoding for PTEN demonstrated reduced intimal area compared with those treated with empty adenovirus and phosphate-buffered saline (1.39 ± 0.11 vs 2.35 ± 0.3 and 2.57 ± 0.4 mm2, P < .05), and the intima/media ratio was lower in saphenous vein grafts treated with adenovirus encoding for PTEN (0.50 ± 0.05 vs 1.43 ± 0.18 and 1.11 ± 0.14, P < .005). PTEN overexpression in vascular smooth muscle cells inhibited platelet-derived growth factor-induced phosphorylation of Akt, a downstream effector of phosphatidylinositol 3-kinase. PTEN-treated vascular smooth muscle cells demonstrated decreased basal, platelet-derived growth factor-stimulated, and serum-stimulated proliferation.ConclusionThis study demonstrates that PTEN overexpression in aortocoronary saphenous vein grafts reduces intimal hyperplasia. The mechanism of this antiproliferative effect in vascular smooth muscle cells is likely due to inhibition of phosphatidylinositol 3-kinase signaling through Akt, with resultant decreases in vascular smooth muscle cell growth and survival. Therefore modulation of the phosphatidylinositol 3-kinase pathway through PTEN overexpression might represent a novel therapy to prevent saphenous vein graft intimal hyperplasia after coronary artery bypass grafting.

Background— Failing human myocardium is characterized by an attenuated contractile response to β-adrenergic receptor (βAR) stimulation due to changes in this signaling cascade, including increased expression and activity of the β-adrenergic receptor kinase (βARK1). This leads to desensitization and downregulation of βARs. Previously, expression of a peptide inhibitor of βARK1 (βARKct) has proven beneficial in several animal models of heart failure (HF). Methods and Results— To test the hypothesis that inhibition of βARK1 could improve β-adrenergic signaling and contractile function in failing human myocytes, the βARKct was expressed via adenovirus-mediated (AdβARKct) gene transfer in ventricular myocytes isolated from hearts explanted from 10 patients with end-stage HF undergoing cardiac transplantation. AdβARKct also contained the marker gene, green fluorescent protein, and successful gene transfer was confirmed via fluorescence and immunoblotting. Compared with uninfected failing myocytes (control), the velocities of both contraction and relaxation in the AdβARKct-treated cells were increased in response to the β-agonist isoproterenol (contraction: 57.5±6.6% versus 37.0±4.2% shortening per second, P P P Conclusions— These results demonstrate that as in animal models of HF, expression of the βARKct can improve contractile function and β-adrenergic responsiveness in failing human myocytes. Thus, βARK1 inhibition may represent a therapeutic strategy for human HF.

Background: There are few data examining the short-term effects of concussions on player performance upon return to play. This study examined changes in on-field performance and the influence of epidemiologic factors on performance and return to play. Hypothesis: On-field performance is different in players who return within 7 days after concussion compared with players who miss at least 1 game. Study Design: Case-control study; Level of evidence, 3. Methods: Players in the National Football League who were active during the 2008 to 2012 seasons were considered for inclusion. Weekly injury reports identified concussed players. All players played in at least 4 games before and after the game of injury (sentinel game) within the year of injury (sentinel year). Players who had missed games secondary to another injury or had sustained a second concussion within the sentinel year were excluded. The players’ league profiles were used to determine age, position, body mass index, career experience, and games missed. ProFootballFocus performance scores determined player ratings. Statistical analysis used 2-sided t tests and both univariate and multivariate logistic regression models. Results: There were a total of 131 concussions in the 124 players who qualified for this study; 55% of these players missed no games. Defensive secondary, wide receiver, and offensive line were the most commonly affected positions. Players who missed at least 1 game were younger and less experienced. Preinjury ProFootballFocus performance scores were similar to postinjury performance in players without games missed (0.16 vs 0.33; P = .129) and players who missed at least 1 game (−0.06 vs 0.10; P = .219). Age, body mass index, experience, and previous concussion did not correlate with changes in postinjury scores ( P > .05). Older, more experienced players and players with late-season concussions were more likely to return to play without missing games ( P < .05). The odds of returning within 7 days increased by 18% for each career year and by 40% for each game before the sentinel game within the sentinel year; these same odds decreased by 85% after introduction of newer treatment guidelines in 2009. Conclusion: No difference in player performance after concussion was found whether the player did or did not miss games before return. Return without missing games may be associated with experience and timing of injury within a season and less likely after newer guidelines.

Level I trauma centers frequently see trauma at or below the ankle, which requires consultation with the orthopedic surgery department. However, as podiatry programs begin to firmly establish themselves in more Level I trauma centers, their consultations increase, ultimately taking those once seen by orthopedic surgery. A review of the literature demonstrates that this paradigm shift has yet to be discussed. The purpose of this study was to determine how many, if any, lower extremity fracture consultations a newly developed podiatry program would take from the orthopedic surgery department. A retrospective review was performed of emergency department records from January 2007 to December 2011. Seventeen different emergency department diagnoses were used to search the database. Ultimately, each patient’s emergency department course was researched. Several trends were noted. First, if trauma surgery was involved, only the orthopedic surgery department was consulted for any injuries at or below the ankle. Second, the emergency department tended to consult the podiatry program only between the hours of 8 am and 6 pm . Third, as the podiatry program became more established, their number of consultations increased yearly, and, coincidentally, the orthopedic surgery department’s consultations decreased. Finally, high-energy traumas involved only the orthopedic surgery department. Whether the orthopedic surgery department or podiatry program is consulted regarding trauma surgery is likely hospital dependent.

Alpha-adrenergic stimulation induces protection in reperfused ischemic (I/R) myocardium 24 hours later. We tested the hypothesis that phenylephrine improves dysfunction after global I/R by limiting cell death not stunning.Rabbits were pretreated with either phenylephrine or vehicle. Twenty-four hours later, isolated hearts underwent either 45 (infarction protocol) or 20 minutes (stunning protocol) of global ischemia before 2 hours of reperfusion (n = 6 per group). Cell death was determined by triphenyl tetrazolium chloride staining (infarction) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) (apoptosis).Compared with vehicle, phenylephrine pretreatment improved post-I/R-developed pressures in hearts after infarction (53.2 +/- 4.0 vs 35.8 +/- 4.1 mm Hg, p = 0.01) but not stunning protocol (64.3 +/- 8.9 vs 57.7 +/- 6.2 mm Hg, p = NS). The improved developed pressure was due to better diastolic recovery. Systolic pressures were similar between groups. Phenylephrine markedly decreased infarction (9.0 +/- 1.9% vs 40.8 +/- 1.8% for vehicle, p0.001) and TUNEL-positive staining. Stunned hearts of either group had less than 3% infarction and no apoptosis.Phenylephrine pretreatment 24 hours before global I/R improves function by limiting infarction but not stunning.

Objective: Previous studies have demonstrated that α1-adrenoceptor activation increases myocardial resistance to ischemic injury 24 hours later. Here we tested the hypothesis that delayed protection is associated with limited infarction and involves altered expression of pro-apoptotic and/or anti-apoptotic proteins. Methods : Rabbits were treated with phenylephrine or an equivalent volume of vehicle (n = 6 per group). Twenty-four hours after pretreatment, isolated hearts were perfused with a bovine erythrocyte suspension in modified Krebs solution, subjected to 45 minutes of global ischemia (37°C), and reperfused for 120 minutes. Infarct size was determined by triphenyltetrazolium chloride staining. Apoptosis was quantified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. Left ventricular tissue from separate groups of animals (n = 5 per group), 24 hours after pretreatment with phenylephrine or vehicle but without ischemia and reperfusion, was analyzed by Western blotting for content of the anti-apoptotic protein, bcl x , and pro-apoptotic protein, bax. Results : Isolated hearts after phenylephrine pretreatment had increased end-reperfusion developed pressures (56.8 ± 4.9 vs 36.2 ± 3.9 mm Hg for vehicle, P = .008) and decreased elevated end-diastolic pressures (26.7 ± 4.5 vs 42.3 ± 5.0 mm Hg for vehicle, P = .04). Phenylephrine pretreatment abrogated infarction (9.9 ± 2.4% vs 42.6 ± 6.3% for vehicle, P = .002) and reduced the number of apoptotic nuclei (24 ± 4.8 vs 51 ± 4.6 for vehicle, P = .038). Analysis by Western blotting showed that the ratio of bcl x to bax protein increased in phenylephrine-pretreated hearts (2.65 ± 0.5 vs 1.0 ± 0.1 for vehicle, P = .008). Conclusion : Delayed myocardial protection to infarction mediated by α1-adrenoceptor activation involves an increased bcl x /bax ratio, thereby limiting apoptotic cell death. (J Thorac Cardiovasc Surg 1999;117:980-6)

Ultrastructural studies of stunned myocardium have shown disorganization and loss of extracellular collagen and increased collagenase activity early after ischemia and reperfusion. The interplay between matrix metalloproteinase 1 (MMP-1) and tissue inhibitor of metalloproteinase 1 (TIMP-1) regulates the turnover of cardiac extracellular matrix fibrillar collagens. However, the gene expression of MMP-1 and TIMP-1 in stunned myocardium is not known. Here, we determined whether altered expression of MMP-1 and TIMP-1 occurs in globally stunned hearts. An isolated nonworking rabbit heart preparation, perfused with a bovine erythrocyte suspension in modified Krebs solution, was used. Two groups were studied: the stunned group was subjected to 20 min of normothermic global ischemia followed by 120 min of normal reperfusion (n = 8), and the control group underwent 140 min of uninterrupted perfusion (n = 7). The developed pressures at the end of reperfusion for ischemic and control hearts were 67.0 +/- 2.73 and 83.1 +/- 1.52 mm Hg (P < 0. 006) respectively. Ribonuclease protection assays of total left ventricular RNA using riboprobes for MMP-1, TIMP-1, and 18S rRNA were performed. A significant decrease (twofold, P < 0.03) in TIMP-1 gene expression was found in the stunned hearts, while MMP-1 mRNA expression was unchanged. Thus, in early stunning, the decrease in TIMP-1 expression could tip the balance favoring enhanced metalloproteinase activity, promoting collagen turnover, and initiating extracellular matrix remodeling. This may contribute to delayed recovery from myocardial stunning.

Background Meniscal tears and associated parameniscal cysts have good outcomes after partial meniscectomy and cyst evacuation. Good outcomes have been noted after partial meniscectomy with recurrent cysts. This investigation asks if partial meniscectomy without meniscal cyst decompression is sufficient for positive patient outcome. Methods Sixteen patients treated between 2005 and 2010 for a meniscal cyst and concomitant meniscal tear. Inclusion criteria were meniscal tear and parameniscal cyst per MRI, no prior surgery on the affected knee, and Outerbridge classification of I/II. Two patients were excluded. Fourteen patients completed the study until final follow-up. Lysholm knee scores were documented at 6 months post-operatively and at final follow-up. Re-evaluation or second surgery of the treated knee was documented. Results Eight lateral cysts and six medial cysts were diagnosed. Eight cysts were associated with a horizontal cleavage tear, while six menisci had a complex tear with a horizontal cleavage component. The average cyst size was 1.3 cm (0.5 to 3.5) at the largest diameter. At 6 months, the average Lysholm knee score was 94.1. At mean 5 years, the average score was 89.1. Patients with medial cysts, cysts greater than 1.0 cm, horizontal cleavage tears, or without simultaneous chondroplasty scored higher in the short and medium-term than their respective counterparts. Conclusions Excellent short and medium-term outcomes can be achieved following partial meniscectomy without cyst decompression for patients with meniscal cysts and associated meniscal tears. Level of evidence Level IV

The authors describe a novel technique of anterograde femoral intramedullary nail fixation for hip fracture using the starting guide pin as a blocking screw. This cost-effective technique uses fluoroscopic radiography to ensure the guidewire is within the posterior aspect of the femur on a lateral view, thereby minimizing the risk of anterior cortical femoral fractures. [ Orthopedics. 2014; 37(3):179–182.]

This study evaluated hippocampal inhibitory function and the level of expression of gamma-aminobutyric acid type A (GABAA) receptor mRNA in an in vivo model of epilepsy. Chronic recurrent limbic seizures were induced in rats using injections of pilocarpine. Electrophysiological studies performed on hippocampal slices prepared from control and epileptic animals 1 to 2 months after pilocarpine injections demonstrated a significant hyperexcitability in the epileptic animals. Reduced levels of mRNA expression for the alpha 2 and alpha 5 subunits of the GABAA receptors were evident in the CA1, CA2, and CA3 regions of the hippocampus of epileptic animals. No decrease in mRNA encoding alpha 1, beta 2, or gamma 2 GABAA receptor subunits was observed. In addition, no change in the mRNA levels of alpha CaM kinase II was seen. Selective decreases in mRNA expression did not correlate with neuronal cell loss. The results indicate that selective, long-lasting reduction of GABAA subunit mRNA expression and increased excitability, possibly reflecting loss of GABAergic inhibition, occur in an in vivo model of partial complex epilepsy.

Background Context Minimally invasive sacroiliac (SI) joint fusion has become increasingly relevant in recent years as a treatment for SI joint pathology. Previous studies have found minimally invasive SI fusion to be an effective and safe treatment option for chronic SI joint pain. However, these studies have been primarily single-center, case-based, or manufacturer-sponsored investigations, and as such their findings are limited to their sample populations. Purpose The aim of this study was to investigate the safety of minimally invasive SI fusion using a large nationwide sample group to more accurately identify complication rates of this increasingly popular procedure. Study Design/Setting This is a retrospective database study. Patient Sample The sample includes patients within the orthopedic subset of Humana database who underwent minimally invasive SI fusion between 2007 and 2014. Outcome Measures Complications and novel lumbar and nerve pathology were the outcome measures. Methods Patients undergoing minimally invasive SI fusion from 2007 to 2014 were identified using the Pearl Diver patient record database (Pearl Diver Technologies, West Conshohocken, PA, USA) from the nationwide private insurance provider Humana Inc. This approach provided access to records of over 18 million patients in every major geographic region of the country. Using the ICD-9 diagnosis codes (International Classification of Diseases 9th edition), data from patient records were analyzed to reveal incidence of postoperative infection, pain, osteomyelitis, joint derangement, urinary tract infection, and novel lumbar and nervous system pathology. Results Four hundred sixty-nine patients (305 female; 164 male) within the Humana insurance database received minimally invasive SI fusion between 2007 and 2014. Data from these patients showed a substantial increase in the use of the procedure over this 7-year period. Among these patients, an overall complication rate of 13.2% (n=62) was seen at 90 days postoperatively and 16.4% (n=77) at 6 months. The number of patients receiving a first time diagnosis of lumbar pathology following minimally invasive SI fusion in the sample population was also analyzed. The incidence of novel lumbar pathology in this population was 3.6% (n=17) at 90 days postoperatively and 5.3% (n=25) at 6 months. Men experienced diagnoses of novel lumbar pathology at higher rates than women within both 90 days (men=6.7%; women≤3.3%) and 6 months (men=9.1%; women≤3.3%) of the procedure (p Conclusions The results of this study show that minimally invasive SI joint fusion could possibly carry higher risks of complications than previously stated. These findings are useful for physicians and patients when considering treatment for chronic SI joint pain.

Adult deformity patients often require fixation to the sacrum and pelvis for construct stability and improved fusion rates. Although certain sacropelvic fixation techniques can be challenging, the availability of intraoperative navigation has made many of these techniques more feasible. In this video case presentation, the authors demonstrate the techniques of S-1 bicortical screw and S-2-alar-iliac screw fixation under intraoperative navigation in a 67-year-old female. This instrumentation placement was part of an overall T-10–pelvis construct for the correction of adult spinal deformity.The video can be found here: https://youtu.be/3HZo-80jQr8.

IntroductionLumbar discectomy is the most commonly performed procedure for treatment of radiculopathy due to lumbar disc herniation. Randomized trials have demonstrated the advantage of surgical re...

Background:Athletic pubalgia is a complex injury that results in loss of play in competitive athletes, especially hockey players. The number of reported sports hernias has been increasing, and the importance of their management is vital. There are no studies reporting whether athletes can return to play at preinjury levels.Purpose:The focus of this study was to evaluate the productivity of professional hockey players before an established athletic pubalgia diagnosis contrasted with the productivity after sports hernia repair.Study Design:Cohort study; Level of evidence, 3.Methods:Professional National Hockey League (NHL) players who were reported to have a sports hernia and who underwent surgery from 2001 to 2008 were identified. Statistics were gathered on the players’ previous 2 full seasons and compared with the statistics 2 full seasons after surgery. Data concerning games played, goals, average time on ice, time of productivity, and assists were gathered. Players were divided into 3 groups: group A incorporated all players, group B were players with 6 or fewer seasons of play, and group C consisted of players with 7 or more seasons of play. A control group was chosen to compare player deterioration or improvement over a career; each player selected for the study had a corresponding control player with the same tenure in his career and position during the same years.Results:Forty-three hockey players were identified to have had sports hernia repairs from 2001 to 2008; ultimately, 80% would return to play 2 or more full seasons. Group A had statistically significant decreases in games played, goals scored, and assists. Versus the control group, the decreases in games played and assists were supported. Statistical analysis showed significant decreases in games played, goals scored, assists, and average time on ice the following 2 seasons in group C, which was also seen in comparison with the control group. Group B (16 players) showed only statistical significance in games played versus the control group.Conclusion:Players who undergo sports hernia surgeries return to play and often perform similar to their presurgery level. Players with over 7 full seasons return but with significant decreases in their overall performance levels. Less veteran players were able to return to play without any statistical decrease in performance and are likely the best candidates for repair once incurring injury.

Background context Adjacent segment disease (ASD) is symptomatic deterioration of spinal levels adjacent to the site of a previous fusion. A critical issue related to ASD is whether deterioration of spinal segments adjacent to a fusion is due to the spinal intervention or due to the natural history of spinal degenerative disease. Purpose The purpose of this review is to summarize the recent clinical literature on adjacent segment disease in light of the natural history, patient-modifiable risk factors, surgical risk factors, sagittal balance, and new technology. Study design This review will evaluate the recent literature on genetic and hereditary components of spinal degenerative disease and potential links to the development of ASD. Methods After a meticulous search of Medline for relevant articles pertaining to our review, we summarized the recent literature on the rate of ASD and the effect of various interventions, including motion preservation, sagittal imbalance, arthroplasty, and minimally invasive surgery. Results The reported rate of ASD after decompression and stabilization procedures is approximately 2% to 3% per year. The factors that are consistently associated with adjacent segment disease include laminectomy adjacent to a fusion and a sagittal imbalance. Conclusions Spinal surgical interventions have been associated with ASD. However, whether such interventions may lead to an acceleration of the natural history of the disease remains questionable.

Activation of excitatory amino acid (EAA) receptors in cultured hippocampal neurons causes down-regulation of the protein ligatin, a receptor for phosphoglycoproteins and a marker protein for membrane-vesicle transport systems. This reduction occurs at both physiologic and excitotoxic levels of glutamate stimulation and is accompanied by a significant decrease in steady state levels of ligatin mRNA. Reduction in ligatin mRNA occurs within 60 min and persists 24 h later. Steady state levels of mRNAs encoding cyclophilin, an ubiquitous cytosolic protein, and neuron specific-enolase (N-SE) are not diminished by glutamate receptor activation, demonstrating that down-regulation of ligatin mRNA was not a result of general catabolism. Further, this reduction in ligatin mRNA occurred without induction of HSP 70. Pharmacological studies using selective antagonists and agonists indicate that this down-regulation of ligatin gene expression is predominantly mediated by theN-methyl- d -aspartate (NMDA) subclass of EAA receptors and that Ca2+ is required. This is the first report that EAA receptor activation in hippocampal neurons can pretranslationally down-regulate gene expression in a rapid and long-lasting manner under physiologic, as well as cytotoxic conditions. The data support the hypothesis that modulation of neuronal gene expression may represent a molecular mechanism mediating some of the long-lasting functional and pathophysiological effects of EAA on cell function.

Previous studies have demonstrated cell cycle-dependent specificities in the interactions of E2F proteins with Rb family members. We now show that the formation of an E2F-p130 complex is unique to cells in a quiescent, G0 state. The E2F-p130 complex does not reform when cells reenter a proliferative state and cycle through G1. The presence of an E2F-p130 complex in quiescent cells coincides with the E2F-mediated repression of transcription of the E2F1 gene, and we show that the E2F sites in the E2F1 promoter are important as cells enter quiescence but play no apparent role in cycling cells. In addition, the decay of the E2F-p130 complex as cells reenter the cell cycle requires the action of G1 cyclin-dependent kinase activity. We conclude that the accumulation of the E2F-p130 complex in quiescent cells provides a negative control of certain key target genes and defines a functional distinction between these G0 cells and cells that exist transiently in G1.

Exposure of hippocampal slices to Mg2+ free media (0 Mg) has been shown to trigger full production of stimulus-induced seizure activity after restoration of physiological conditions [1]. In the present study employing hippocampal entorhinal cortical slices (HEC), spontaneous epileptiform discharges (SEDs) were induced using 0 Mg treatment following the return of the slices to physiological conditions. To evaluate the effect of sustained epileptiform activity on gene expression in this HEC slice preparation, changes in mRNA levels of the GABAA alpha 1 and alpha 2 and beta CaM Kinase II subunits were measured using in situ hybridization. HEC slices were incubated in oxygenated artificial cerebrospinal fluid (ACSF) in the presence or absence of Mg2+ for 3 h, then placed in oxygenated ACSF containing Mg2+ for up to 3 h. Control slices were maintained in Mg2+ containing ACSF for up to 6 h. Recurrent SEDs were observed in 0 Mg pre-treated slices while no epileptiform discharges were seen in control slices. Following induction of SEDs by 0 Mg pre-treatment, a significant decrease in mRNA encoding GABAA alpha 2 was found in the CA1, CA2, CA3 and dentate gyrus (DG) regions of the hippocampus for up to 3 h after treatment. Levels of mRNA for GABAA alpha 1 and beta CaM Kinase II were not affected. The results document a decrease in GABAA alpha 2 gene expression following the induction of SEDs in the HEC slice preparation and suggest that rapid changes in neuronal gene expression may contribute to long lasting excitability changes associated with the induction of epilepsy.