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Selected AbstractsConversion from a calcineurin inhibitor to everolimus therapy in maintenance liver transplant recipients: A prospective, randomized, multicenter trialLIVER TRANSPLANTATION, Issue 10 2009Paolo De Simone Calcineurin inhibitors (CNIs) contribute to renal dysfunction following liver transplantation. This prospective, randomized, multicenter, 6-month study (with an additional 6 months of follow-up) evaluated whether everolimus with CNI reduction or discontinuation would improve renal function in maintenance liver transplant recipients experiencing CNI-related renal impairment. Patients started everolimus therapy with CNI reduction or discontinuation (n = 72) or continued receiving standard-exposure CNI (n = 73). At month 6, 80% of the patients who had converted to everolimus had discontinued the CNI. The mean change in creatinine clearance (CrCl) from baseline to month 6 was similar between groups (everolimus, 1.0 ± 10.2 mL/minute; controls, 2.3 ± 7.8 mL/minute; P = 0.46), so the primary study endpoint (8 mL/minute difference in the change in CrCl) was not achieved. Among patients who continued everolimus according to the protocol, the mean increase in CrCl was 2.1 (n = 53) and 3.8 mL/minute (n = 38) at months 6 and 12, respectively, versus 2.4 (n = 68) and 3.5 mL/minute in controls (n = 51). The high frequency of CNI dose reductions in controls (77% of the patients) and the relatively long mean time post-transplant (>3 years) likely contributed to the small difference in CrCl. Biopsy-proven acute rejection occurred in 1.4% of the patients in each group, with no graft losses. Study drug discontinuation was higher in everolimus-treated patients, and adverse events were more frequent. These data demonstrate that everolimus allows for discontinuation or a major reduction of CNI exposure in liver allograft recipients suffering CNI-related renal dysfunction without a loss of efficacy. Trials targeting earlier conversion post-transplantation are required to confirm the efficacy and safety of everolimus for improving renal function after liver transplantation. Liver Transpl 15:1262,1269, 2009. © 2009 AASLD. [source] Oral versus Intravenous Opioid Dosing for the Initial Treatment of Acute Musculoskeletal Pain in the Emergency DepartmentACADEMIC EMERGENCY MEDICINE, Issue 12 2008James R. Miner MD Abstract Objectives:, The objective was to compare the time to medication administration, the side effects, and the analgesic effect at sequential time points after medication administration of an oral treatment strategy using oxycodone solution with an intravenous (IV) treatment strategy using morphine sulfate for the initial treatment of musculoskeletal pain in emergency department (ED) patients. Methods:, This was a prospective randomized clinical trial of patients >6 years old who were going to receive IV morphine sulfate for the treatment of musculoskeletal pain but did not yet have an IV. Consenting patients were randomized to have the treating physician order either 0.1 mg/kg morphine sulfate IV or 0.125 mg/kg oxycodone orally in a 5 mg/5 mL suspension as their initial treatment for pain. The time from the placement of the order to the administration of the medication was recorded. Pain was measured using a 100-mm visual analog scale (VAS) and recorded at 0, 10, 20, 30 and 40 minutes after drug administration. Results:, A total of 405 eligible patients were identified during the study period; 328 (81.0%) patients consented to be in the study. A total of 158 patients were randomized to the IV morphine sulfate treatment group, and 162 were randomized to the oral oxycodone treatment group. Of the patients who were randomized to IV therapy, 34 were withdrawn from the study prior to drug administration; leaving 125 patients in the IV group for analysis. Of the patients who randomized to oral therapy, 22 were withdrawn from the study prior to drug administration, leaving 140 patients for analysis. No serious adverse events were detected. There was a 12-minute difference between the median time of the order and the administration of oral oxycodone (8.5 minutes) and IV morphine (20.5 minutes). The mean percent change in VAS score was larger for patients in the IV therapy group than those in the oral therapy group at 10 and 20 minutes. At 30 and 40 minutes, the authors could no longer detect a difference. The satisfaction scale score was higher after treatment for the morphine group (median = 4; interquartile range [IQR] = 4 to 5) than for the oxycodone group (median = 4; IQR = 2 to 5; p = 0.008). Conclusions:, The oral loading strategy was associated with delayed onset of analgesia and decreased patient satisfaction, but a shorter time to administration. The oral loading strategy using an oxycodone solution provided similar pain relief to the IV strategy using morphine 30 minutes after administration of the drug. Oral 0.125 mg/kg oxycodone represents a feasible alternative to 0.1 mg/kg IV morphine in the treatment of severe acute musculoskeletal pain when difficult or delayed IV placement greater than 30 minutes presents a barrier to treatment. [source] The origami of thioredoxin-like foldsPROTEIN SCIENCE, Issue 10 2006Jonathan L. Pan Abstract Origami is the Japanese art of folding a piece of paper into complex shapes and forms. Much like origami of paper, Nature has used conserved protein folds to engineer proteins for a particular task. An example of a protein family, which has been used by Nature numerous times, is the thioredoxin superfamily. Proteins in the thioredoxin superfamily are all structured with a ,-sheet core surrounded with ,-helices, and most contain a canonical CXXC motif. The remarkable feature of these proteins is that the link between them is the fold; however, their reactivity is different for each member due to small variations in this general fold as well as their active site. This review attempts to unravel the minute differences within this protein family, and it also demonstrates the ingenuity of Nature to use a conserved fold to generate a diverse collection of proteins to perform a number of different biochemical tasks. [source] Early colonization of non-submerged dental implants in patients with a history of advanced aggressive periodontitisCLINICAL ORAL IMPLANTS RESEARCH, Issue 1 2006Annemarie L. De Boever Abstract: The aim of the study was to evaluate the early colonization of non-submerged implants over a 6-month period in partially edentulous patients treated for advanced aggressive periodontal disease. In 22 patients treated for advanced aggressive periodontitis and in a supportive maintenance program for a period between 12 and 240 months at implant surgery, a total of 68 non-submerged dental implants were installed. Patients had a plaque score below 20%, and less than 20% of the pockets around the teeth were bleeding on probing (BOP). Using DNA-probes (micro-IDent®), the presence and concentration of five periodontal pathogens (Actinobacillus actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Tannerella forsythensis (Tf) and Treponema denticola (Td)) were determined in the five deepest pockets of the rest dentition pre-operatively and after 6 months as well as five places around each implant 10 days, 1 month, 3 months and 6 months after surgery. In each patient, a test to determine the genotype interleukin-1 (IL-1) was performed (PST , micro-IDent®). After 6 months, no difference in microbial composition as compared with baseline was found around the teeth in five patients, in 12 minute differences and in five patients important differences were observed. Ten days after surgery, three patients had a complete similar bacterial composition between teeth and implants. In 14 patients, the composition was fairly similar, while large differences in composition and concentration occurred in five patients. This microbiota around the implants remained almost unchanged over a 6-month period and did not hamper the clinical and radiographic osseointegration and did not lead to peri-implantitis, mucositis or initiation of bone destruction. [source] |