Infected Necrosis in Severe Pancreatitis - Combined Nonsurgical Multi-Drainage with Directed Transabdominal High-Volume Lavage in Critically Ill Patients

Background: Infection of pancreatic necrosis is a life-threatening complication during the course of acute pancreatitis. In critically ill patients, surgical or extended endoscopic interventions are associated with high morbidity and mortality. Minimally invasive procedures on the other hand are often insufficient in patients suffering from large necrotic areas containing solid or purulent material. We present a strategy combining percutaneous and transgastric drainage with continuous high-volume lavage for treatment of extended necroses and liquid collections in a series of patients with severe acute pancreatitis. Patients and Methods: Seven consecutive patients with severe acute pancreatitis and large confluent infected pancreatic necrosis were enrolled. In all cases, the first therapeutic procedure was placement of a CT-guided drainage catheter into the fluid collection surrounding peripancreatic necrosis. Thereafter, a second endosonographically guided drainage was inserted via the gastric or the duodenal wall. After communication between the separate drains had been proven, an external to internal directed high-volume lavage with a daily volume of 500 ml up to 2,000 ml was started. Results: In all patients, pancreatic necrosis/liquid collections could be resolved completely by the presented regime. No patient died in the course of our study. After initiation of the directed high-volume lavage, there was a significant clinical improvement in all patients. Double drainage was performed for a median of 101 days, high-volume lavage for a median of 41 days. Several endoscopic interventions for stent replacement were required (median 8). Complications such as bleeding or perforation could be managed endoscopically, and no subsequent surgical therapy was necessary. All patients could be dismissed from the hospital after a median duration of 78 days. Conclusion: This approach of combined percutaneous/endoscopic drainage with high-volume lavage shows promising results in critically ill patients with extended infected pancreatic necrosis and high risk of surgical intervention. Neither surgical nor endoscopic necrosectomy was necessary in any of our patients. Copyright (C) 2009 S. Karger AG, Basel and IA

The Intriguing Effects of Substituents in the N-Phenethyl Moiety of Norhydromorphone: A Bifunctional Opioid from a Set of “Tail Wags Dog” Experiments

This work is licensed under a Creative Commons Attribution 4.0 International License.(−)-N-Phenethyl analogs of optically pure N-norhydromorphone were synthesized and pharmacologically evaluated in several in vitro assays (opioid receptor binding, stimulation of [35S]GTPγS binding, forskolin-induced cAMP accumulation assay, and MOR-mediated β-arrestin recruitment assays). “Body” and “tail” interactions with opioid receptors (a subset of Portoghese’s message-address theory) were used for molecular modeling and simulations, where the “address” can be considered the “body” of the hydromorphone molecule and the “message” delivered by the substituent (tail) on the aromatic ring of the N-phenethyl moiety. One compound, N-p-chloro-phenethynorhydromorphone ((7aR,12bS)-3-(4-chlorophenethyl)-9-hydroxy-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one, 2i), was found to have nanomolar binding affinity at MOR and DOR. It was a potent partial agonist at MOR and a full potent agonist at DOR with a δ/μ potency ratio of 1.2 in the ([35S]GTPγS) assay. Bifunctional opioids that interact with MOR and DOR, the latter as agonists or antagonists, have been reported to have fewer side-effects than MOR agonists. The p-chlorophenethyl compound 2i was evaluated for its effect on respiration in both mice and squirrel monkeys. Compound 2i did not depress respiration (using normal air) in mice or squirrel monkeys. However, under conditions of hypercapnia (using air mixed with 5% CO2), respiration was depressed in squirrel monkeys.NIDA grant P30 DA13429NIDA grant DA039997NIDA grant DA018151NIDA grant DA035857NIDA grant DA047574NIH Intramural Research Programs of the National Institute on Drug AbuseNational Institute of Alcohol Abuse and AlcoholismNIH Intramural Research Programs of the National Institute on Drug AbuseNIH Intramural Research Program through the Center for Information TechnologyNIH Intramural Research Programs of the National Institute on Drug Abus

Combined sedation with midazolam/propofol for gastrointestinal endoscopy in elderly patients

<p>Abstract</p> <p>Background</p> <p>Although gastrointestinal endoscopy with sedation is increasingly performed in elderly patients, data on combined sedation with midazolam/propofol are very limited for this age group.</p> <p>Methods</p> <p>We retrospectively analyzed 454 endoscopic procedures in 347 hospitalized patients ≥ 70 years who had received combined sedation with midazolam/propofol. 513 endoscopic procedures in 397 hospitalized patients < 70 years during the observation period served as controls. Characteristics of endoscopic procedures, co-morbidity, complications and mortality were compared.</p> <p>Results</p> <p>Elderly patients had a higher level of co-morbidity and needed lower mean propofol doses for sedation. We observed no major complication and no difference in the number of minor complications. The procedure-associated mortality was 0%; the 28-day mortality was significantly higher in the elderly (2.9% vs. 1.0%).</p> <p>Conclusions</p> <p>In this study on elderly patients with high level co-morbidity, a favourable safety profile was observed for a combined sedation with midazolam/propofol with a higher sensitivity to propofol in the elderly.</p

Prevalence of non Helicobacter pylori species in patients presenting with dyspepsia

<p>Abstract</p> <p>Background</p> <p>Helicobacter species associated with human infection include <it>Helicobacter pylori, Helicobacter heilmannii </it>and <it>Helicobacter felis </it>among others. In this study we determined the prevalence of <it>H. pylori </it>and non-<it>Helicobacter pylori </it>organisms <it>H. felis and H. heilmannii </it>and analyzed the association between coinfection with these organisms and gastric pathology in patients presenting with dyspepsia. Biopsy specimens were obtained from patients with dyspepsia on esophagogastroduodenoscopy (EGD) for rapid urease test, histology and PCR examination for Helicobacter genus specific 16S rDNA, <it>H. pylori </it>phosphoglucosamine mutase (<it>glmM</it>) and urease B (<it>ureB</it>) gene of <it>H. heilmannii </it>and <it>H. felis</it>. Sequencing of PCR products of <it>H. heilmannii </it>and <it>H. felis </it>was done.</p> <p>Results</p> <p>Two hundred-fifty patients with dyspepsia were enrolled in the study. The mean age was 39 ± 12 years with males 162(65%). Twenty-six percent (66 out of 250) were exposed to cats or dogs. PCR for Helicobacter genus specific 16S rDNA was positive in 167/250 (67%), <it>H. pylori glmM </it>in 142/250 (57%), <it>H. heilmannii </it>in 17/250 (6%) and <it>H. felis </it>in 10/250 (4%), respectively. All the <it>H. heilmannii </it>and <it>H. felis </it>PCR positive patients were also positive for <it>H. pylori </it>PCR amplification. The occurrence of coinfection of <it>H. pylori </it>and <it>H. heilmannii </it>was 17(6%) and with <it>H. felis </it>was 10(4%), respectively. Only one out of 66 exposed to pets were positive for <it>H. heilmannii </it>and two for <it>H. felis</it>. Histopathology was carried out in 160(64%) of 250 cases. Chronic active inflammation was observed in 53(56%) (p = 0.001) of the patients with <it>H. pylori </it>infection alone as compared to 3(37%) (p = 0.73) coinfected with <it>H. heilmannii </it>and <it>H. pylori </it>and 3(60%) coinfected with <it>H. felis </it>and <it>H. pylori </it>(p = 0.66). Intestinal metaplasia was observed in 3(3%)(p = 1.0) of the patients with <it>H. pylori </it>infection alone as compared to 2(25%) (p = 0.02) coinfected with <it>H. heilmannii </it>and <it>H. pylori </it>and 1(20%) coinfected with <it>H. felis </it>and <it>H. pylori </it>(p = 0.15).</p> <p>Conclusion</p> <p>The prevalence of <it>H. heilmannii </it>and <it>H. felis </it>was low in our patients with dyspepsia. Exposure to pets did not increase the risk of <it>H. heilmannii </it>or <it>H. felis </it>infection. The coinfection of <it>H. pylori </it>with <it>H. heilmannii </it>was seen associated with intestinal metaplasia, however this need further confirmation.</p

Lack of association between gene polymorphisms of Angiotensin converting enzyme, Nod-like receptor 1, Toll-like receptor 4, FAS/FASL and the presence of Helicobacter pylori-induced premalignant gastric lesions and gastric cancer in Caucasians

<p>Abstract</p> <p>Background</p> <p>Several polymorphisms of genes involved in the immunological recognition of <it>Helicobacter pylori </it>and regulating apoptosis and proliferation have been linked to gastric carcinogenesis, however reported data are partially conflicting. The aim of our study was to evaluate potential associations between the presence of gastric cancer (GC) and high risk atrophic gastritis (HRAG) and polymorphisms of genes encoding <it>Angiotensin converting enzyme </it>(<it>ACE</it>), <it>Nod-like receptor 1 </it>(<it>NOD1</it>), <it>Toll-like receptor 4 </it>(<it>TLR4</it>) and <it>FAS/FASL</it>.</p> <p>Methods</p> <p>Gene polymorphisms were analyzed in 574 subjects (GC: n = 114; HRAG: n = 222, controls: n = 238) of Caucasian origin. <it>ACE I/D </it>(rs4646994), <it>NOD1 796G>A </it>(rs5743336), <it>TLR4 3725G>C </it>(rs11536889), <it>FAS 1377G>A </it>(rs2234767), <it>FAS 670A>G </it>(rs1800682) and <it>FASL 844T>C </it>(rs763110) were genotyped by different PCR approaches and restriction fragment length polymorphism analysis.</p> <p>Results</p> <p>Frequencies of genotypes in our study are similar to the data reported on subjects of Caucasian ethnicity. There was a tendency for <it>NOD1 796G/G </it>genotype to be associated with increased risk of HRAG (62.4% <it>vs</it>. 54.5% in controls, <it>p </it>= 0.082). <it>FAS 670G/G </it>genotype was more frequent in HRAG when compared to controls, 23.9% and 17.2% respectively, however it failed to reach significance level (<it>p </it>= 0.077). We did not find any significant associations for all polymorphisms in relation to GC or HRAG. <it>NOD1 796G>A </it>and <it>TLR4 3725G>C </it>gene polymorphisms were also not associated with <it>Helicobacter pylori </it>infection.</p> <p>Conclusions</p> <p><it>ACE, NOD1, TRL4 </it>and <it>FAS/FASL </it>gene polymorphisms are not linked with gastric carcinogenesis in Caucasians, and therefore they should not be considered as potential biomarkers for identifying individuals with higher risk for GC.</p

The EUI flight instrument of Solar Orbiter: from optical alignment to end-to-end calibration

The Extreme Ultraviolet Imager (EUI) instrument for the Solar Orbiter mission will image the solar corona in the extreme ultraviolet (17.1 nm and 30.4 nm) and in the vacuum ultraviolet (121.6 nm) spectral ranges. The development of the EUI instrument has been successfully completed with the optical alignment of its three channels’ telescope, the thermal and mechanical environmental verification, the electrical and software validations, and an end-toend on-ground calibration of the two-units’ flight instrument at the operating wavelengths. The instrument has been delivered and installed on the Solar Orbiter spacecraft, which is now undergoing all preparatory activities before launch