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Study Design Retrospective Review Objective The aim of this study was to evaluate the incidence and magnitude of pedicle asymmetry as well as spinous process deviation in the healthy lumbar spine. Summary of Background Data Minimally invasive spine surgery relies on fluoroscopic imaging as bony landmarks used for instrumentation are not exposed. The precision of techniques used to determine vertebral body rotation intraoperatively may be confounded by anatomic variation or pathology. Here, we investigate the physiologic variation in different anatomic structures of the lumbar spine used for percutaneous pedicle screw placement. Methods 100 normal lumbar CT scans, without evidence of acute deformity, significant spondylosis, scoliosis, or spondylolisthesis were reviewed to assess for pedicle height, width and spinous process angle (SPA) to compare symmetry between right and left sided pedicles for each vertebral body. Spinous process deviation of ≥5° in the axial plane was considered a relevant finding and the magnitude of offset from midline was calculated using the deviation angle and spinous process length. Results Analysis of CT scans found that 17.5% of lumbar spinous processes had an average angular variation ≥5°. This calculates to a clinically significant 3.53 mm average offset of spinous processes from midline in 17.5% of lumbar vertebrae. Pedicle height and width measurements did not show statistically or clinically significant variation when comparing right to left lumbar pedicles. Conclusion These results suggest that using the spinous process as a fluoroscopic landmark during intraoperative imaging to determine neutral rotation of lumbar vertebrae can be an unreliable technique. Rotational alignment can be determined more reliably by comparing left to right pedicle symmetry. These findings should be considered when selecting an operative technique to assess neutral vertebral alignment during percutaneous pedicle screw instrumentation.

For patients with end-stage lung diseases, lung transplantation is the only available therapeutic option. However, the number of suitable donor lungs is insufficient and lung transplants are complicated by significant graft failure and complications of immunosuppressive regimens. An alternative to classic organ replacement is desperately needed. Engineering of bioartificial organs using either natural or synthetic scaffolds is an exciting new potential option for generation of functional pulmonary tissue for human clinical application. Natural organ scaffolds can be generated by decellularization of native tissues; these acellular scaffolds retain the native organ ultrastructure and can be seeded with autologous cells towards the goal of regenerating functional tissues. Several decellularization strategies have been employed for lungs; however, there is no consensus on the optimal approach. A variety of cell types have been investigated as potential candidates for effective recellularization of acellular lung scaffolds. Candidate cells that might be best utilized are those which can be easily and reproducibly isolated, expanded in vitro, seeded onto decellularized matrices, induced to differentiate into pulmonary lineage cells, and which survive to functional maturity. Whole lung cell suspensions, endogenous progenitor cells, embryonic and adult stem cells and induced pluripotent stem (iPS) cells have been investigated for their applicability to repopulate acellular lung matrices. Ideally, patient-derived autologous cells would be used for lung recellularization as they have the potential to reduce the need for post-transplant immunosuppression. Several studies have performed transplantation of rudimentary bioengineered lung scaffolds in animal models with limited, short-term functionality but much further study is needed.

Universal ganciclovir (GCV) prophylaxis is a strategy aimed at reducing cytomegalovirus (CMV) infection and delaying the development of bronchiolitis obliterans syndrome (BOS). However, the optimal duration of GCV prophylaxis remains unclear. We report our experience with GCV prophylaxis administered indefinitely and its effect on CMV pneumonitis, BOS and survival after lung transplantation (LT).One hundred fifty-one patients surviving100 days after LT were analyzed. GCV was given to 130 CMV donor- or recipient-seropositive patients. Data from 90 patients who received indefinite GCV prophylaxis (IND) and 40 patients who discontinued their GCV prophylaxis (STOP) were compared.CMV pneumonitis occurred in 16%, 8%, 17% and 19% of patients in the D+R+, D-R+, D+R- and D-R- groups, respectively. In the STOP cohort, 15 of 40 patients developed CMV pneumonitis (median time 79 days) after GCV was stopped. Ten of these 15 patients developed BOS (median time 116 days) after discontinuing GCV. The risk of CMV pneumonitis in the STOP cohort was significantly higher when GCV prophylaxis was discontinued within the first year. Cumulative incidence of CMV pneumonitis in the IND and STOP groups at 5 years was 2% and 57%, respectively (p0.001). BOS-free survival and survival were similar across both groups.Indefinite GCV prophylaxis prevents CMV pneumonitis in 98% of LT recipients. Thirty-eight percent of patients discontinuing prophylaxis developed CMV pneumonitis, 50% of whom progressed to BOS within 1 year. Continuing ganciclovir prophylaxis indefinitely after lung transplantation should be considered.

Background Infections are common after lung transplantation. This report analyzes infections and associated pathogens identified in 202 lung transplant recipients. Methods Infections were tallied according to sites of infection and associated pathogen(s). Infection events were also categorized by post-operative Days 0 to 100, 101 to 365, and after 365, and normalized to 100 patient-days before and after bronchiolitis obliterans syndrome (BOS). Results From November 1990 to November 2005, 202 patients received 208 lung transplants. The follow-up was 702.4 patient-years. A total of 178 lung transplant patients developed 859 infections, with 944 pathogens identified. Infections were in the lung in 559 (65.1%), mucocutaneous (skin, wound, catheter-related, and oral) in 88 (10.2%), in the blood in 85 (9.8%), and in other sites (urine, bowel, eye, and peritoneum) in 127 (14.8%). Most lung pathogens were bacterial (83.6%), and 57.9% were Pseudomonas aeruginosa . Fungi comprised 10.6%, with Aspergillus spp the most common (67.1%) isolate. Cytomegalovirus pneumonitis was seen in 4.3% of respiratory infections. BOS was diagnosed in 87 patients (43.1% of the total). Of all infections seen in the BOS population, there were 0.42 episodes/100 patient-days and 0.70 episodes/100 patient-days before and after BOS, respectively ( p = 0.5). Conclusions These data provide an updated infection profile in the ganciclovir era after lung transplantation. When compared with pre-ganciclovir times, post-transplant cytomegalovirus infection incidence has notably declined, with filamentous fungi emerging as prevalent pathogens in its place. Such findings are important for refining management of infections in order to offer more stringent treatment against aggressive pathogens.

Background Cystic fibrosis (CF) lung disease is the major cause of mortality in CF patients. Lung transplantation remains a valid therapeutic option. It is unknown whether CF patients receiving healthy lungs have an equal susceptibility to infections when compared with non-CF lung transplant patients. Herein we present the largest analyses to date of the post-operative infection profiles of 60 CF and 60 non-CF lung transplant patients. Methods Bilateral allogeneic lung transplantations and post-transplant management were performed according to standard clinical procedures. Post-operative infections were diagnosed by conventional methods based on clinical symptoms and laboratory cultures. Results Sixty CF lung-transplant patients developed 278 post-operative respiratory infections, from which 307 pathogens were isolated. Pseudomonas aeruginosa predominantly occupied 60.3%, followed by Mycobacteria spp (7.2%), Aspergillus spp (5.9%) and Staphylococcus spp (5.5%). However, 60 non-CF transplant patients had 154 respiratory infections with 165 pathogens isolated. Pseudomonas aeruginosa was noted in 38.2%, followed by Aspergillus spp (9.7%), Staphylococcus spp (9.7%) and Mycobacteria spp (9.1%). The CF group demonstrated a significantly higher frequency of Pseudomonas respiratory infections than the non-CF group. Interestingly, no significant differences were detected in any infections from other systems including blood, sinuses, skin, wounds, oral cavity, bowel, eyes, peritoneal cavity and urinary tract. Moreover, the CF lung transplant patients had significantly less time free from Pseudomonas infections. Conclusions The normal lungs implanted into CF patients had significantly higher susceptibility to Pseudomonas infections than those into non-CF patients, suggesting that defective innate immunity outside the lungs contributes to CF lung pathogenesis.

For the last sixty years, personality and personality traits (or characteristics) have been studied, researched, and applied to managing individuals and organizations. Some practitioners say that personality research predates the Roman Empire and the Great Greek Philosophers. The use of personality identification as a form of diversity leadership and possible technology is becoming more popular in helping people and organizations assign tasks within the organization as well as to enhance the performance in the organization. The Myers Briggs Type Instrument (MBTI) is one personality tool that strategically links diversity to cultural DNA and enhances the performance educational, medical, business, and military leadership worldwide. There are other personality instruments that can provide similar results, but the authors have chosen the MBTI to best depict how personality can easily be applied to diverse systems to measure individual and organizational change. The impact of these and other diversity characteristics, competencies, and technologies must be filtered through formal instructional systems, design processes, and evaluation procedures to help leadership identify strengths and weaknesses within the organization regardless of the type of organization. There will be a need for varied evaluation and measures to help sustain effectiveness and outcomes. The authors present a brief framework for these measures.

The present research entails turbulent reacting flow being simulated inside a low-density polyethylene tubular reactor using computational fluid dynamics techniques. The effects of initiator mass fraction and initiator injection speed on the stability of the reactor have been studied. The reactor and injector should be designed such that the ethylene does not undergo the potential decomposition reaction; this reaction is exothermic and violent. The products of the decomposition must be vented as a safety measure. ANSYS FLUENT has been used to simulate this reacting flow problem. Both decomposition reaction and polymerization reaction are entered into the software along with their kinetic information. A high product yield of polymer without initiating the ethylene decomposition reaction is expected. Optimal mass fraction of initiator and optimal injection velocity were determined in order to maximize product and maintain the stability of the low-density polyethylene tubular reactor.Copyright © 2012 by ASME

Acute lung injury (ALI) describes one or more initiating assaults either directly to the lungs or systemically that, if not treated in a timely manner, ultimately progresses to the development of acute respiratory distress syndrome (ARDS) a condition which is characterized by atelectasis, pulmonary hypertension, and an intense, overwhelming inflammatory response that leads to obliterating pulmonary fibrosis and ultimately respiratory failure. The long-term complications associated with ALI/ARDS can be subverted if the fibrotic phase of the disease is suppressed; therefore, it is essential to control inflammation in such a way that endogenous self-protection mechanisms are maintained while not allowing escalating inflammatory damage to occur in the local environment of the lungs. Current treatment strategies focus on optimal ventilator management and treatment of the underlying condition. Cell-based approaches are an attractive option for directed therapeutic intervention for ALI/ARDS. In particular, mesenchymal stem cells (MSCs) from bone marrow, adipose, umbilical cord, and lung tissue as well as induced pluripotent stem (iPS) cells have been shown to facilitate lung repair in several animal models of ALI. The exact mechanism(s) by which these cells accomplish this feat are as yet unknown; however, mounting evidence suggests that they possess potent immunomodulatory and antimicrobial capabilities which diminish the injury-induced inflammatory responses and reduce infection-mediated ALI, respectively, in these various models. Both direct delivery of stem cells to the lung and systemic administration have been somewhat effective, suggesting that stem cells utilize paracrine mechanisms, at least in part, to perform these functions. Aside from their endogenous ability to suppress inflammation and infection, gene-modified MSCs and iPS cells have recently been used as vehicles for carrying anti-inflammatory agents to the lung. Taken together, stem cell therapy is a promising alternative to current therapeutic intervention for ALI/ARDS.

Huperzine A is potentially superior to pyridostigmine bromide as a pretreatment for nerve agent intoxication because it inhibits acetylcholinesterase both peripherally and centrally, unlike pyridostigmine, which acts only peripherally. Using rhesus monkeys, we evaluated the time course of acetylcholinesterase and butyrylcholinesterase inhibition following four different doses of -(-)huperzine A: 5, 10, 20, and 40 microg/kg. Acetylcholinesterase inhibition peaked 30 min after intramuscular injection and varied dose dependently, ranging from about 30% to 75%. Subsequently, cognitive-behavioral functioning was also evaluated at each dose of huperzine A using a six-item serial-probe recognition task that assessed attention, motivation, and working memory. Huperzine did not impair performance, but physostigmine did. The results demonstrate that huperzine A can selectively and reversibly inhibit acetylcholinesterase without cognitive-behavioral side effects, thus warranting further study.

Huperzine A is potentially superior to pyridostigmine bromide as a pretreatment for nerve agent intoxication because it inhibits acetylcholinesterase both peripherally and centrally, unlike pyridostigmine, which acts only peripherally. Using rhesus monkeys, we evaluated the time course of acetylcholinesterase and butyrylcholinesterase inhibition following four different doses of -(-)huperzine A: 5, 10, 20, and 40 ug/kg. Acetylcholinesterase inhibition peaked 30 minutes after intramuscular injection and varied dose dependently, ranging from about 30% to 75%. Subsequently, cognitive-behavioral functioning was also evaluated at each dose of huperzine A using a six-item serial-probe recognition task that assessed attention, motivation, and working memory. The results demonstrate that huperzine A can selectively and reversibly inhibit acetylcholinesterase without cognitive-behavioral side effects, thus warranting further study.

Background Among the many potential risk factors influencing the development of bronchiolitis obliterans syndrome (BOS), acute cellular rejection is the most frequently identified. Despite the unique susceptibility of the lung allograft to pathogens, the association with respiratory tract infections remains unclear. In this study we analyze the role respiratory tract infections have on the development of BOS after lung transplantation. Methods Data from a single center were analyzed from 161 lung recipients transplanted from November 1990 to November 2005, and who survived >180 days. Univariate and multivariate Cox regression analyses were performed using BOS development and the time-scale was reported with hazard ratios (HRs) and confidence intervals (CIs). Results Significant findings by univariate analysis per 100 patient-days prior to BOS onset included acute rejection, cytomegalovirus (CMV) pneumonitis, Gram-negative respiratory tract infections, Gram-positive respiratory tract infections and fungal pneumonias. Multivariate analysis indicated acute rejection, Gram-negative, Gram-positive and fungal pneumonias with HRs (CI) of 84 (23 to 309), 6.6 (1.2 to 37), 6,371 (84 to 485,000) and 314 (53 to 1,856) to be associated with BOS, respectively. Acute rejection, CMV pneumonitis, Gram-positive pneumonia and fungal pneumonitis in the first 100 days had HRs (CI) of 1.8 (1.1 to 3.2), 3.1 (1.3 to 6.9), 3.8 (1.5 to 9.4) and 2.1 (1.1 to 4.0), respectively, and acute rejection and fungal pneumonitis in the late post-operative period with HRs (CI) of 2.3 (1.2 to 4.4) and 1.5 (1.1 to 1.9), respectively. Conclusions In addition to acute rejection, pneumonias with GP, GN and fungal pathogens occurring prior to BOS are independent determinants of chronic allograft dysfunction. Early recognition and treatment of these pathogens in lung transplant recipients may improve long-term outcomes after transplantation.

Introduction Adipose-derived stem cells (ASCs) have emerged as important regulators of inflammatory/immune responses in vitro and in vivo and represent attractive candidates for cell-based therapies for diseases that involve excessive inflammation. Acute lung injury (ALI) is an inflammatory condition for which treatment is mainly supportive due to lack of effective therapies. In this study, the therapeutic effects of ASC-based therapy were assessed in vivo by comparison of the anti-inflammatory properties of both human and murine ASCs in a mouse model of lipopolysaccharide (LPS)-induced ALI. Methods Human ASCs (hASCs) or mouse ASCs (mASCs) were delivered to C57Bl/6 mice (7.5 × 105 total cells/mouse) by oropharyngeal aspiration (OA) four hours after the animals were challenged with lipopolysaccharide (15 mg/kg). Mice were sacrificed 24 and 72 hours after LPS exposure, and lung histology examined for evaluation of inflammation and injury. Bronchoalveolar lavage fluid (BALF) was analyzed to determine total and differential cell counts, total protein and albumin concentrations, and myeloperoxidase (MPO) activity. Cytokine expression in the injured lungs was measured at the steady-state mRNA levels and protein levels for assessment of the degree of lung inflammation. Results Both human and mouse ASC treatments provided protective anti-inflammatory responses. There were decreased levels of leukocyte (for example neutrophil) migration into the alveoli, total protein and albumin concentrations in BALF, and MPO activity after the induction of ALI following both therapies. Additionally, cell therapy with both cell types effectively suppressed the expression of proinflammatory cytokines and increased the anti-inflammatory cytokine interleukin 10 (IL-10). Overall, the syngeneic mASC therapy had a more potent therapeutic effect than the xenogeneic hASC therapy in this model. Conclusions Treatment with hASCs or mASCs significantly attenuated LPS-induced acute lung injury in mice. These results suggest a potential benefit for using an ASC-based therapy to treat clinical ALI and may possibly prevent the development of acute respiratory distress syndrome (ARDS).