Girelli R.,Pancreatic Unit Casa Of Cura Pederzoli |
Prejano S.,University of Verona |
Cataldo I.,University of Verona |
Corbo V.,University of Verona |
And 3 more authors.
Radiology and Oncology | Year: 2015
Background. Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease generally refractory to standard chemotherapeutic agents; therefore improvements in anticancer therapies are mandatory. A major determinant of therapeutic resistance in PDAC is the poor drug delivery to neoplastic cells, mainly due to an extensive fibrotic reaction. Electroporation can be used in vivo to increase cancer cells' local uptake of chemotherapeutics (electrochemotherapy, ECT), thus leading to an enhanced tumour response rate. In the present study, we evaluated the in vivo effects of reversible electroporation in normal pancreas in a rabbit experimental model. We also tested the effect of electroporation on pancreatic cancer cell lines in order to evaluate their increased sensitivity to chemotherapeutic agents. Materials and methods. The application in vivo of the European Standard Operating Procedure of Electrochemotherapy (ESOPE) pulse protocol (1000 V/cm, 8 pulses, 100 μs, 5 KHz) was tested on the pancreas of normal New Zealand White Rabbits and short and long-term toxicity were assessed. PANC1 and MiaPaCa2 cell lines were tested for in vitro electrochemotherapy experiments with and without electroporation. Levels of cell permeabilization were determined by flow cytometry, whereas cell viability and drug (cisplatin and bleomycin) sensitivity of pulsed cells were measured by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Results. In healthy rabbits, neither systemic nor local toxic effects due to the electroporation procedure were observed, demonstrating the safety of the optimized electric parameters in the treatment of the pancreas in vivo. In parallel, we established an optimized protocol for ECT in vitro that determined an enhanced anti-cancer effect of bleomycin and cisplatin with respect to treatment without electroporation. Conclusions. Our data suggest that electroporation is a safe procedure in the treatment of PDAC because it does not affect normal pancreatic parenchyma, but has a potentiating effect on cytotoxicity of bleomycin in pancreatic tumour cell lines. Therefore, ECT could be considered as a valid alternative for the local control of non-resectable pancreatic cancer. © 2015, Association of Radiology and Oncology. All rights reserved.
Holmes N.,Advanced Orthopedic Technologies |
Cronholm P.F.,University of Pennsylvania |
Duffy A.J.,Widener University |
Webner D.,Crozer Keystone Healthplex Sports Medicine Institute
Clinical Journal of Sport Medicine | Year: 2013
OBJECTIVE: To determine prevalence of nonsteroidal anti-inflammatory drug (NSAID) use in college football players and whether positions sustaining the most contact would use NSAIDs more frequently. DESIGN: Prospective cross-sectional study. SETTING: American college football programs. PATIENTS: An anonymous survey was given to 211 college football players before the season. INDEPENDENT VARIABLE: Use of NSAIDs. MAIN OUTCOME MEASURES: The dependent variables are the different patterns in NSAID usage among positions and the frequency of NSAID use before and after the season. RESULTS: Of the athletes surveyed, 95.7% had or were using NSAIDs. Athletes first used NSAIDs in junior high school (45.6%), high school (48.5%), or college (5.8%). Athletes were separated into high (daily or weekly) or low (monthly or rarely) utilizers of NSAIDs. High utilization of NSAIDs was more frequent during the season (50.0%) than in the off-season (14.6%), P < 0.001. High NSAID utilization among all players was more prevalent after than before games (32.7% vs 10.9%, P = 0.002). Players with a higher body mass index (BMI; >28) were significantly higher utilizers of NSAIDs, reporting higher rates of use in season compared with other players (57.4% vs 39.5%, P = 0.011, OR = 2.06). CONCLUSIONS: Use of NSAIDs in collegiate football players is common. It is concerning that those athletes with the highest cardiovascular risk (ie, elevated body mass index) use greater amounts of NSAIDs. Further investigation is needed to delineate the short-term and long-term consequences of NSAID utilization in young athletes. Copyright © 2013 by Lippincott Williams & Wilkins.
PubMed | Advanced Orthopedic Technologies, University of Bologna and Rizzoli Orthopaedic Institute
Type: Journal Article | Journal: Cytotherapy | Year: 2016
Osteoarthritis (OA) can affect every joint, especially the knee. Given the complexity of this pathology, OA is difficult to treat with current therapies, which only relieve pain and inflammation and are not capable of restoring tissues once OA has started. Currently, researchers focus on finding a therapeutic strategy that may help to arrest disease progression. The present narrative review gives an overview of the genes involved in the development and progression of OA, assessing in vivo studies performed in knock-out mice affected by OA, to suggest new therapeutic strategies. The article search was performed on the PubMed database and www.webofknowledge.com website with the following keywords: knee osteoarthritis AND knockout mice. The included studies were in English and published from 2005 to 2015. Additional papers were found within the references of the selected articles. In the 55 analyzed in vivo studies, genes mainly affected chondrocyte homeostasis, inflammatory processes, extracellular matrix and the relationship between obesity and OA. Genes are defined as inducing, preventing and not influencing OA. This review shows that joint homeostasis depends on a variety of genetic factors, and preventing or restoring the loss of a gene encoding for protective proteins, or inhibiting the expression of proteins that induce OA, might be a potential therapeutic approach. However, conclusions cannot be drawn because of the wide variability concerning the technique used for OA induction, the role of the genes, the method for tissue evaluations and the lack of assessments of all joint tissues.
PubMed | Advanced Orthopedic Technologies, Rizzoli Orthopaedic Institute, CNR Institute of Structure of Matter, Romana Film Sottili and 5 more.
Type: Journal Article | Journal: Materials science & engineering. C, Materials for biological applications | Year: 2016
Titanium implants coated with a 500nm nanostructured layer, deposited by the Ion Plating Plasma Assisted (IPPA) technology, composed of 60% graphitic carbon, 25% titanium oxides and 15% titanium carbide were implanted into rabbit femurs whilst into the controlateral femurs uncoated titanium implants were inserted as control. At four time points the animals were injected with calcein green, xylenol orange, oxytetracycline and alizarin. After 2, 4 and 8weeks femurs were removed and processed for histology and static and dynamic histomorphometry for undecalcified bone processing into methylmethacrylate, sectioned, thinned, polished and stained with Toluidine blue and Fast green. The overall bone-implant contacts rate (percentage of bone-implant contacts/weeks) of the TiC coated implant was 1.6 fold than that of the uncoated titanium implant. The histomorphometric analyses confirmed the histological evaluations. More precisely, higher Mineral Apposition Rate (MAR, m/day) (p<0.005) and Bone Formation Rate (BFR, m
Gebauer G.,Advanced Orthopedic Technologies |
Osterman M.,Thomas Jefferson University |
Harrop J.,Thomas Jefferson University |
Vaccaro A.,Thomas Jefferson University
Clinical Orthopaedics and Related Research | Year: 2012
Background Strict criteria have been used before removing cervical collars in patients with injuries who have midline pain or are unable to be reliably examined. This sometimes leads to prolonged immobilization in cervical collars or use of MRI to rule out injury. Several studies suggest a collar may be removed in the absence of fractures, dislocation, or pathologic subluxation on a cervical CT scan. This may avoid the morbidity of prolonged cervical immobilization or cost of advanced imaging study but risks devastating consequences from missing injuries. Case Description We report a patient with a cervical spinal cord injury after removal of a collar after a CT scan was misinterpreted as normal. Retrospective review of the CT showed subtle signs of widening between the spinous processes of the injured level, a finding easily missed without the use of further imaging studies. Literature Review Several articles suggest cervical collars may be safely removed from awake and alert patients and in patients who cannot be reliably examined after a negative CT scan without the need for further imaging. Purposes and Clinical Relevance CT scans are excellent at detecting bony injuries but not ligamentous injuries. Removing cervical collars based on CT scans alone may be expeditious, but some injuries may be missed without further imaging. Our case demonstrates the catastrophic consequences of missing a cervical spine injury and emphasizes the need for maintaining the cervical collar in high-risk patients until proper imaging can be obtained. © The Association of Bone and Joint Surgeons® 2012.
Gebauer G.,Advanced Orthopedic Technologies |
Anderson D.G.,Thomas Jefferson University
Seminars in Spine Surgery | Year: 2011
Compared with open procedures, minimally invasive spine surgery allows spinal abnormalities to be addressed through smaller incisions with less soft-tissue damage and postoperative pain, which may lead to shorter hospitalizations and earlier mobility for the patient. However, minimally invasive spine procedures require advanced techniques, mandate specialized equipment, provide decreased visualization, and are associated with a steep learning curve. Although studies have shown similar complication rates for the 2 approaches, minimally invasive surgery may be associated with decreased fusion rates, increased dural injury rates, and inadequate decompression compared with conventional surgical techniques. This review addresses the complications associated with minimally invasive spine procedures and provides tips for prevention. © 2011 Elsevier Inc.
Zaslav K.,Advanced Orthopedic Technologies |
McAdams T.,Stanford University |
Scopp J.,Peninsula Orthopedic Associates |
Theosadakis J.,University of Arizona |
And 2 more authors.
Cartilage | Year: 2012
Objective: Articular cartilage injury is common after athletic injury and remains a difficult treatment conundrum both for the surgeon and athlete. Although recent treatments for damage to articular cartilage have been successful in alleviating symptoms, more durable and complete, long-term articular surface restoration remains the unattained goal. In this article, we look at both new ways to prevent damage to articular surfaces as well as new techniques to recreate biomechanically sound and biochemically true articular surfaces once an athlete injures this surface. This goal should include reproducing hyaline cartilage with a well-integrated and flexible subchondral base and the normal zonal variability in the articular matrix. Results: A number of nonoperative interventions have shown early promise in mitigating cartilage symptoms and in preclinical studies have shown evidence of chondroprotection. These include the use of glucosamine, chondroitin, and other neutraceuticals, viscosupplementation with hyaluronic acid, platelet-rich plasma, and pulsed electromagnetic fields. Newer surgical techniques, some already in clinical study, and others on the horizon offer opportunities to improve the surgical restoration of the hyaline matrix often disrupted in athletic injury. These include new scaffolds, single-stage cell techniques, the use of mesenchymal stem cells, and gene therapy. Conclusion: Although many of these treatments are in the preclinical and early clinical study phase, they offer the promise of better options to mitigate the sequelae of athletically induced cartilage. © SAGE Publications 2012.
Pomeroy G.,Mercy Hospital |
Wilton J.,Valley Regional Hospital |
Anthony S.,Advanced Orthopedic Technologies
Journal of the American Academy of Orthopaedic Surgeons | Year: 2015
Occurrences of entrapment neuropathies of the lower extremity are relatively infrequent; therefore, these conditions may be underappreciated and difficult to diagnose. Understanding the anatomy of the peripheral nerves and their potential entrapment sites is essential. A detailed physical examination and judicious use of imaging modalities are also vital when establishing a diagnosis. Once an accurate diagnosis is obtained, treatment is aimed at reducing external pressure, minimizing inflammation, correcting any causative foot and ankle deformities, and ultimately releasing any constrictive tissues. © 2014 by the American Academy of Orthopaedic Surgeons.
Anthony S.,Advanced Orthopedic Technologies |
Munk R.,University of Toledo |
Skakun W.,Ohio State University |
Masini M.,University of Michigan
Journal of the American Academy of Orthopaedic Surgeons | Year: 2015
Multiple epiphyseal dysplasia is a genotypically and phenotypically heterogeneous disorder affecting the epiphysis of long bones. Inheritance may be autosomal dominant or autosomal recessive. Autosomal dominant variants include mutations of the collagen oligomeric matrix protein, collagen type IX α-1, collagen type IX α-2, collagen type IX α-3, and matrilin-3 genes. The autosomal recessive variant is caused by a mutation of the sulfate transporter gene SLC26A2. These mutations cause disorganized endochondral ossification of the epiphysis, ultimately leading to destruction of the articular cartilage. Patients typically present in childhood, but some may not present until early adulthood. A presumptive diagnosis can be made with clinical history, physical examination, detailed family history, and radiographic findings. Definitive diagnosis requires genetic testing. Treatment is based on the age of the patient, the amount of limb deformity, the level of joint destruction, and the needs of the patient. Children can greatly benefit from limb realignment procedures, and adults can have excellent outcomes with joint arthroplasty. © 2015 by the American Academy of Orthopaedic Surgeons.