Secure and effective gene delivery system of plasmid DNA coated by polynucleotide

Polynucleotides are anionic macromolecules which are expected to transfer into the targeted cells through specific uptake mechanisms. So, we developed polynucleotides coating complexes of plasmid DNA (pDNA) and polyethylenimine (PEI) for a secure and efficient gene delivery system and evaluated their usefulness. Polyadenylic acid (polyA), polyuridylic acid (polyU), polycytidylic acid (polyC), and polyguanylic acid (polyG) were examined as the coating materials. pDNA/PEI/polyA, pDNA/PEI/polyU, and pDNA/PEI/polyC complexes formed nanoparticles with a negative surface charge although pDNA/PEI/polyG was aggregated. The pDNA/PEI/polyC complex showed high transgene efficiency in B16-F10 cells although there was little efficiency in pDNA/PEI/polyA and pDNA/PEI/polyU complexes. An inhibition study strongly indicated the specific uptake mechanism of pDNA/PEI/polyC complex. Polynucleotide coating complexes had lower cytotoxicity than pDNA/PEI complex. The pDNA/PEI/polyC complex showed high gene expression selectively in the spleen after intravenous injection into mice. The pDNA/PEI/polyC complex showed no agglutination with erythrocytes and no acute toxicity although these were observed in pDNA/PEI complex. Thus, we developed polynucleotide coating complexes as novel vectors for clinical gene therapy, and the pDNA/PEI/polyC complex as a useful candidate for a gene delivery system

Efficacy of hip arthroscopy in the diagnosis and treatment of synovial osteochondromatosis : a case report and literature review

Here we report a rare case of synovial osteochondromatosis of the hip and provide a brief review of the literature. A 37-year-old woman was referred to our department with a 3-year history of right hip pain. At initial consultation, she complained of pain upon standing and when sitting down, occasional pain at rest and nocturnal pain in the right hip, and worsening of the pain at premenstruum. The range of motion of the affected hip was totally limited by pain. Plain radiography revealed a slightly calcified (or ossified) lesion at the acetabular fossa of the right hip. Computed tomography showed clusters of loose bodies filling the acetabular fossa. Synovial osteochondromatosis was suspected and she underwent hip arthroscopic surgery. Complete resection was performed using the lateral and anterior portals. Postoperatively, her symptoms disappeared entirely and she was discharged 4 days after surgery. The patient regained full range of motion of the right hip and follow-up CT revealed no remaining loose bodies in the right hip. Hip arthroscopy is considered to be effective for the diagnosis and treatment of synovial osteochondromatosis of the hip and is minimally invasive

New diagnostic criteria and severity assessment of acute cholangitis in revised Tokyo guidelines

Background: The Tokyo Guidelines for the management of acute cholangitis and cholecystitis were published in 2007 (TG07) and have been widely cited in the world literature. Because of new information that has been published since 2007, we organized the Tokyo Guidelines Revision Committee to conduct a multicenter analysis to develop the updated Tokyo Guidelines (TG13). Methods/materials : We retrospectively analyzed 1,432 biliary disease cases where acute cholangitis was suspected. The cases were collected from multiple tertiary care centers in Japan. The 'gold standard' for acute cholangitis in this study was that one of the three following conditions was present: (1) purulent bile was observed; (2) clinical remission following bile duct drainage; or (3) remission was achieved by antibacterial therapy alone, in patients in whom the only site of infection was the biliary tree. Comparisons were made for the validity of each diagnostic criterion among TG13, TG07 and Charcot's triad. Results: The major changes in diagnostic criteria of TG07 were re-arrangement of the diagnostic items and exclusion of abdominal pain from the diagnostic list. The sensitivity improved from 82.8 % (TG07) to 91.8 % (TG13). While the specificity was similar to TG07, the false positive rate in cases of acute cholecystitis was reduced from 15.5 to 5.9 %. The sensitivity of Charcot's triad was only 26.4 % but the specificity was 95.6 %. However, the false positive rate in cases of acute cholecystitis was 11.9 % and not negligible. As for severity grading, Grade II (moderate) acute cholangitis is defined as being associated with any two of the significant prognostic factors which were derived from evidence presented recently in the literature. The factors chosen allow severity assessment to be performed soon after diagnosis of acute cholangitis. Conclusion: TG13 present a new standard for the diagnosis, severity grading, and management of acute cholangitis. © 2012 The Author(s).link_to_subscribed_fulltex

New diagnostic criteria and severity assessment of acute cholecystitis in revised Tokyo guidelines

Background: The Tokyo Guidelines for the management of acute cholangitis and cholecystitis (TG07) were published in 2007 as the world's first guidelines for acute cholangitis and cholecystitis. The diagnostic criteria and severity assessment of acute cholecystitis have since been widely used all over the world. A validation study of TG07 has shown that the diagnostic criteria for acute cholecystitis are highly reliable but that the definition of definite diagnosis is ambiguous. In addition, considerable new evidence referring to acute cholecystitis as well as evaluations of TG07 have been published. Consequently, we organized the Tokyo Guidelines Revision Committee to evaluate TG07, recognize new evidence, and conduct a multi-center analysis to revise the guidelines (TG13). Methods and materials: We retrospectively analyzed 451 patients with acute cholecystitis from multiple tertiary care centers in Japan. All 451 patients were first evaluated using the criteria in TG07. The "gold standard" for acute cholecystitis in this study was a diagnosis by pathology. The validity of TG07 diagnostic criteria was investigated by comparing clinical with pathological diagnosis. Results: Of 451 patients evaluated, a total of 227 patients were given a diagnosis of acute cholecystitis by pathological examination (prevalence 50.3 %). TG07 criteria provided a definite diagnosis of acute cholecystitis in 224 patients. The sensitivity of TG07 diagnostic criteria for acute cholecystitis was 92.1 %, and the specificity was 93.3 %. Based on the preliminary results, new diagnostic criteria for acute cholecystitis were proposed. Using the new criteria, the sensitivity of definite diagnosis was 91.2 %, and the specificity was 96.9 %. The accuracy rate was improved from 92.7 to 94.0 %. In regard to severity grading among 227 patients, 111 patients were classified as Mild (Grade I), 104 as Moderate (Grade II), and 12 as Severe (Grade III). Conclusion: The proposed new diagnostic criteria achieved better performance than the diagnostic criteria in TG07. Therefore, the proposed criteria have been adopted as new diagnostic criteria for acute cholecystitis and are referred to as the 2013 Tokyo Guidelines (TG13). Regarding severity assessment, no new evidence was found to suggest that the criteria in TG07 needed major adjustment. As a result, TG07 severity assessment criteria have been adopted in TG13 with minor changes. © 2012 The Author(s).link_to_subscribed_fulltex

Percutaneous Endoscopic Lumbar Discectomy for a Huge Herniated Disc Causing Acute Cauda Equina Syndrome : A Case Report

Microsurgery for lumbar disc herniation that requires surgical intervention has been well described. The methods vary from traditional open discectomy to minimally invasive techniques. All need adequate preanesthetic preparation of patients as general anesthesia is required for the procedure, and nerve monitoring is necessary to prevent iatrogenic nerve injury. Conventional surgical techniques sometimes require the removal of the corresponding lamina to assess the nerve root and herniated disc, and this may increase the risk for posterior instability of the vertebral body. Should this occur, fusion surgery may be needed, further increasing morbidity and cost. We present here a case of lumbar herniated disc fragments causing acute cauda equina syndrome that were endoscopically resected through a transforaminal approach in an awake patient under local anesthesia. Percutaneous endoscopic discectomy under local anesthesia proved to be a better alternative to open back surgery as it made immediate intervention possible, was associated with fewer perioperative complications and morbidity, minimized soft tissue damage, and allowed early rehabilitation with a better outcome and greater patient satisfaction. In addition to these advantages, percutaneous endoscopic discectomy protects other approaches that may be needed in subsequent surgeries, whether open or minimally invasive

Hybrid technique of cortical bone trajectory and pedicle screwing for minimally invasive spine reconstruction surgery : A technical note

The pedicle screw (PS) system is widely used for spinal reconstruction. Recently, screw insertion using the cortical bone trajectory (CBT) technique has been reported to provide increased holding strength of the vertebra, even in an osteoporotic spine. CBT is also beneficial due to its low invasiveness. We have been performing hybrid reconstruction with CBT at the cranial level and PS at the caudal level based on the concept of minimal invasiveness. We applied this hybrid technique to 6 cases of degenerative spondylolisthesis. Surgery was completed with a small skin incision of around 5-6 cm, which is shorter than that of the conventional PS procedure. The mean percent slippage before surgery was 19.8%, and this was reduced to 3.9% after surgery and almost maintained 3 months after surgery. Furthermore, no major surgical complications were observed. Here, we introduce the minimally invasive hybrid technique of CBT-PS. Surgeons should be aware of the procedure as an option for minimally invasive lumbar spine reconstructive surgery

State of the art : Intraoperative neuromonitoring in spinal deformity surgery

Application of deformity correction spinal surgery has increased substantially over the past three decades in parallel with improvements in surgical techniques. Intraoperative neuromonitoring (IOM) techniques, including somatosensory evoked potentials (SEPs), muscle evoked potentials (MEPs), and spontaneous electromyography (free-run EMG), have also improved surgical outcome by reducing the risk of iatrogenic neural injury. In this article, we review IOM techniques and their applications in spinal deformity surgery. We also summarize results of selected studies including hundreds of spinal correction surgeries. These studies indicate that multimodal IOM of both motor and sensory responses is superior to either modality alone for reducing the incidence of neural injury during surgery

Foraminoplastic transforaminal percutaneous endoscopic discectomy at the lumbosacral junction under local anesthesia in an elite rugby player

Percutaneous endoscopic discectomy (PED) is the least invasive disc surgery available at present. The procedure can be performed under local anesthesia and requires only an 8 mm skin incision. Furthermore, damage to the back muscle is considered minimal, which is particularly important for disc surgery in athletes. However, employing the transforaminal (TF) PED approach at the lumbosacral junction can be challenging due to anatomical constraints imposed by the iliac crest. In such cases, foraminoplasty is required in addition to the standard TF procedure. A 28-year-old man who was a very active rugby player visited us complaining of lower back and left leg pain. His visual analog scale (VAS) score for pain was 8/10 and 3/10, respectively. MRI revealed a herniated nucleus pulposus at L5-S level. TF-PED was planned ; however, the anatomy of the iliac crest was later found to prevent access to the herniated mass. Foraminoplasty was therefore performed to enlarge the foramen, thereby allowing a cannula to be passed through the foramen into the canal without causing exiting nerve injury. The herniated mass was then successfully removed via the TF-PED procedure. Pain resolved after surgery, and his VAS score decreased to 0/10 for both back and leg pain. The patient returned to full rugby activity 8 weeks after surgery. In conclusion, even with an intracanalicular herniated mass at the lumbosacral junction, a TF-PED procedure is possible if additional foraminoplasty is adequately performed to enlarge the foramen