Kuo-Chuan Hung

Gene knockdown of the N-methyl-D-aspartate receptor NR1 subunit with subcutaneous small interfering RNA reduces inflammation-induced nociception in rats.

Background:Spinal N-methyl-d-aspartate receptors have been demonstrated to play an important role in the facilitation and maintenance of nociception. To avoid adverse effects of blocking N-methyl-d-aspartate receptors in the central nervous system, blocking N-methyl-d-aspartate receptor in peripheral nervous system is an ideal alternative. Transfection of small interfering RNAs (siRNAs) into cells has been revealed to provide potent silencing of specific genes. In this study, the authors examined the effect of subcutaneous injection of siRNA targeting the NR1 subunit of the N-methyl-d-aspartate receptor on silencing NR1 gene expression and subsequently abolishing inflammatory nociception in rats. Methods:Male Sprague-Dawley rats received intradermal injection of NR1 siRNA and underwent injection of formalin or complete Freunds adjuvant. The flinch response and mechanical hypersensitivity by von Frey filaments were assessed. Then the messenger RNA and protein of NR1 in skin and dorsal root ganglion were analyzed. Results:The results revealed that subcutaneous injection of 1 nmol NR1 siRNA effectively diminished the nociception induced by formalin and complete Freunds adjuvant stimuli and attenuated the level of NR1 messenger RNA and protein in skin and ipsilateral dorsal root ganglion. The antinociception effect and the inhibition of NR1 expression persisted for about 7 days after administration of NR1 siRNA. Conclusions:The data of this study suggest that NR1 siRNA has potential therapeutic value in the treatment of inflammatory pain induced or maintained by peripheral nociceptor activity and support the potential application of this method to the study of nociceptive processes and target the validation of pain-associated genes.

MicroRNA-based therapy in pain medicine: Current progress and future prospects

MicroRNAs (miRNAs) are small noncoding RNA molecules of 18-25 nucleotides in length that regulate gene expression involved in fundamental cell processes. The induction and chronification of pain is associated with many expressional changes in pain-related proteins. miRNA has the potential to regulate gene and protein expression associated with the induction and chronification of pain. Thus, miRNAs might have promise in therapy and as a diagnostic and prognostic biomarker in pain medicine. The application of miRNA has been an emerging field in pain research in recent years. Many studies focusing on the regulation of miRNAs under different tissue and nociceptive stimuli have been performed in recent years. In this review, we intend to introduce the most recent research in the field of miRNA related with pain medicine such as the expression and function of miRNA in different animal pain model, the challenge of application and delivery of miRNA in vivo, the potential toxic effects of miRNA and future problems in clinical application that need to be resolved. This review focuses on the results of miRNA in animal studies and the prospect for future success.

Single-session Laparoscopic Total Urinary Tract Exenteration Without Repositioning for Multifocal Urothelial Carcinoma in Dialysis-dependent Patients

OBJECTIVES To report our experience of single-session, en bloc, laparoscopic total urinary tract exenteration in dialysis-dependent patients with multifocal urothelial carcinoma. METHODS From June 2005 to April 2008, 5 dialysis-dependent patients (4 women and 1 man) diagnosed with synchronous upper urinary tract and bladder urothelial carcinoma underwent single-session, en bloc, laparoscopic total urinary tract exenteration. Bilateral nephroureterectomy was facilitated by rotating the operating table with or without alternative inflation of the tourniquet cuffs on either side of the patients back to allow adequate spontaneous bowel displacement by gravity, thereby avoiding the need to reposition the patient. After completing bilateral nephroureterectomy, we performed radical cystectomy with the patient in the Trendelenburg position. All specimens, including the 2 kidneys, ureters, and bladder, were collected in an endobag and were intended to be retrieved using the Pfannenstiel incision in male patients and the vaginal route in the female patients. The demographic and perioperative information were collected and analyzed. RESULTS All the laparoscopic procedures were completed successfully without major complications. Although 1 patient developed a minor complication owing to paralytic ileus, she recovered after conservative treatment. The continuity of all the urothelial epithelium was maintained intact throughout the procedure to avoid tumor spillage. CONCLUSIONS In our experience, laparoscopic total urinary tract exenteration is a technically feasible and safe alternative modality to the open counterpart to treat dialysis-dependent patients with end-stage renal disease with multifocal urothelial carcinoma for experienced surgeons with advanced laparoscopic skills. Furthermore, it can be performed successfully without the need for repositioning the patient, and this probably decreased the incidence of associated complication in the high-risk patients.

Lentiviral vector‐encoded microRNA‐based shRNA‐mediated gene knockdown of N‐methyl‐D‐aspartate receptors in skin reduces pain

RNA polymerase II promoters that drive the expression of rationally designed primary microRNA‐based shRNA, for example, shRNAmir, can produce more potent gene knockdown than RNA polymerase III promoters. Antagonists of peripheral N methyl‐D‐aspartate (NMDA) receptors that do not interfere with central glutamate processing would prevent the development of adverse central nervous system effects. Thus, in this study, we examined the effects of gene silencing and antinociception on formalin‐ and Complete Freunds adjuvant (CFA)‐induced pain in rats by subcutaneously injecting a lentiviral vector encoding a shRNAmir that targets the NR1 subunit of the NMDA receptor.

Difficult fiber-optic intubation in a patient with giant neck masses: The role of McCoy laryngoscope in elevating compressed laryngeal aperture

Airway management in patients with giant neck masses is usually a challenge to anesthesiologists. A giant neck mass could compress the airway and thus impede endotracheal intubation. We encountered a situation where the giant neck masses of a patient pushed the epiglottis posteriorly toward the posterior pharyngeal wall and compressed the laryngeal aperture narrowing after anesthetic induction, causing direct laryngoscopic intubation and sequential fiber-optic intubation failed. The neck masses twisted the aryepiglottic fold tortuously and clogged the laryngeal aperture tightly, making a flexible fiber-optic bronchoscope unable to pass through the laryngeal aperture. Later, we utilized a McCoy laryngoscope alternately to lift the compressed larynx up and away from the posterior pharyngeal wall, creating a passage and completing endotracheal intubation successfully with the aid of a gum elastic bougie. Our case suggested that the tilting tip blade of the McCoy laryngoscope could lever the tongue base up against the tumor mass compression to improve laryngeal views and facilitate endotracheal intubation when a difficult fiber-optic intubation was encountered on a compressed laryngeal aperture.

Use of the Rusch Flexi-Slip Stylet for Patients With Difficult Insertion of the ProSeal™ Laryngeal Mask Airway

The ProSeal laryngeal mask airway (PLMA) offers a more effective seal and is easier for gastric tube placement to prevent aspiration than the classical laryngeal mask airway. However, it is more difficult to insert with the digital and introducer tooling techniques. The Rusch Flexi-Slip stylet (RFSS) is an accessory intubation tool that consists of a malleable coated wire and a soft atraumatic tip. It has been reported that it can facilitate easier insertion of the PLMA. Here, we report two cases in which the PLMA could not be inserted correctly on the initial attempts, and with successful placement of the PLMA after using an RFSS. In the first case, three attempts to insert the PLMA with the digital and introducer tooling techniques were unsuccessful. The second case was known to be difficult for PLMA placement because, in a previous operation, PLMA insertion for general anesthesia was unsuccessful, and in that instance required endotracheal intubation for general anesthesia. In both cases, the PLMA was successfully inserted using the RFSS technique, without difficulty. The RFSS technique offers several advantages for PLMA insertion, including the provision of effective support and a soft tip for the PLMA insertion. Other techniques to facilitate the insertion of the PLMA, including priming the drain tube with a guide are discussed. We recommend that the RFSS technique offers an effective method for cases with difficult insertion of the PLMA.

Acute Airway Obstruction in the Nonoperated Lung Following Intravenous Administration of Tranexamic Acid During Pneumonectomy

From the Department of Anesthesiology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan. Address reprint requests to: Kuo-Chuan Hung, MD, 1, E-Da Road, Jiau-shu Tsuen, Yan-Chau Shiang, Kaohsiung, Taiwan, 824. E-mail: ed102605@gmail.com

A modified device for removing large regurgitation volume during tracheal intubation

To the Editor Gastric regurgitation occasionally occurs during tracheal intubation, sometimes involving a large amount of gastric contents, including significant particulate matter. The regurgitated material quickly fills the posterior pharynx, obscuring the view of the glottis and leading to significant pulmonary aspiration. Immediate, effective removal of this regurgitated material is important to maintain a clear airway and avoid the consequences of aspiration. Food particles, however, may easily obstruct standard suction cannulas, which have relatively small ports, making it difficult to remove a large regurgitated volume. Previous reports have demonstrated that an endotracheal tube (ETT) could function as a suction device to clear the airway. However, additional equipment is needed to connect the ETT to a suction source, and it may not be immediately available in the operating room. We herein describe a modified suction technique that allows expeditious clearance of regurgitated vomitus during tracheal intubation. A suction device is assembled as shown in the Figure. The Opti-Port, a right-angle, double-swivel connector (Figure A) of a double-lumen tube (Broncho-Cath; Mallinckrodt, Athlone, Ireland), is attached to the ETT. The side-arm plastic tube of the swivel connector is then attached to the suction system (Figure B). This assembly enables the ETT to function as a suction route when the regurgitation volume is large. In the absence of regurgitation, the ETT can then be passed through the glottis and used conventionally. The operator’s finger is used to occlude the bronchoscope port on the swivel connector to control the suctioning. Once it is used for suctioning, the ETT should be replaced with a new ETT. In addition, if needed, a stylet or other bougie can also be inserted through the bronchoscope port into the ETT lumen, allowing airway manipulation in the usual fashion (Figure B). It can be removed quickly if there is a large amount of regurgitated material. This method readily permits suctioning of large-volume, particulate regurgitation during tracheal intubation. As the Opti-Port swivel connector is usually nearby in the operating room, this easy-to-assemble, modified suction device may be helpful for managing patients at high risk of gastric regurgitation.