Stenosis of the gastroenterostomy after laparoscopic gastric bypass occurred in 3.1 % of the patients in this series. It can be successfully and safely treated with endoscopic balloon dilation with good long-term follow-up.
The first potent inhibitors of glutamate racemase (MurI) enzyme that show whole cell antibacterial activity are described. Optically pure 4-substituted D-glutamic acid analogues with (2R,4S) stereochemistry and bearing aryl-, heteroaryl-, cinnamyl-, or biaryl-methyl substituents represent a novel class of glutamate racemase inhibitors. Exploration of the D-Glu core led to the identification of lead compounds (-)-8 and 10. 2-Naphthylmethyl derivative 10 was found to be a potent competitive inhibitor of glutamate racemase activity (K(i) = 16 nM, circular dichroism assay; IC(50) = 0.1 microg/mL high-performance liquid chromatography (HPLC) assay). Thorough structure-activity relationship (SAR) studies led to benzothienyl derivatives such as 69 and 74 with increased potency (IC(50) = 0.036 and 0.01 microg/mL, respectively, HPLC assay). These compounds showed potent whole cell antibacterial activity against S. pneumoniae PN-R6, and good correlation with the enzyme assay. Compounds 69, 74 and biaryl derivative 52 showed efficacy in an in vivo murine thigh infection model against Streptococcus pneumoniae. Data described herein suggest that glutamate racemase may be a viable target for developing new antibacterial agents.
Introduction: the elevated risk of complications and technical complexity of endoscopic submucosal dissection (ESD) has limited its implementation in our medical system.Objective: to design and evaluate a training program for learning the ESD technique.Methods: four endoscopists with no experience with ESD underwent a 4-step training program: 1) review of the existing literature, didactic material, and theoretical aspects of ESD; 2) ESD training in an ex-vivo animal model; 3) ESD training in an in-vivo animal model (supervised by ESD expert); and 4) ESD performance in a patient. A standard gastroscope and an ESD knife (IT, Flex or Hook-knife Olympus ® ) were employed. The classical ESD technique was performed: rising of the lesion, circumferential incision, and submucosal dissection.Results: ex-vivo animal model: 6 x swine stomach/esophagus -cost < 100 euro; 6 x ESD: antrum (n = 2), body (n = 3) and fundus/cardia (n = 1)-; size of resected specimen: 4-10 cm; ESD duration: 105-240 minutes; therapeutic success: 100%; complications: perforation (1/6: 16%) sealed with clips. In-vivo animal model: 6 ESD (antrum/body of stomach: 4; esophagus: 2); size: 2-5 cm; duration: 40-165 minutes; success: 100%; complications: 0%. Patient: ESD of a gastric lesion located in the antrum/body; size: 3 cm; duration 210 minutes; a complete resection was achieved; no complications.Conclusions: the results of the present study support the usefulness of this model for learning ESD in our system. Key words: Endoscopic submucosal dissection. ESD. Submucosal resection. Large endoscopic resection.
INTRODUCTIONEndoscopic mucosal resection (EMR) consists of resecting a superficial tumor of the gastrointestinal tract (esophagus, stomach, colon or rectum) by endoscopic means with curative intention (R0 resection) (1-5). An EMR-resected lesion may be submitted for pathological examination. One of the advantages of EMR compared with surgical resection is its lower morbidity/mortality and cost. At present EMR has become widely available in clinical practice in both Asian and Western countries (1-5). However, EMR presents a number of limitations: a) technical difficulty; b) risk for complications: bleeding (2-29%), perforation (0.36%) and stenosis (mainly in the esophagus); and c) restricted to superficial lesions with no lymphatic spread and size < 1-1.5 cm (1-8). Lesions with a diameter > 1.5 cm cannot be completely resected with a single EMR procedure, and repeated mucosectomies (several fragments) or endoscopic submucosal dissection (ESD) (allowing to resect the entire lesion in a single piece) will be required (2). It is generally assumed that it is better to resect tumoral lesions in single pieces, as we can be sure the tumor has been completely resected, and it also facilitates sample orientation at the time of the pathology study (8)(9)(10)(11)(12)(13)(14)(15). Furthermore, ESD allows to perfom wider and deeper resections versus EMR (2). However, the learning curve for ESD (high technical difficulty) is longer (compared with EMR), and compli...
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