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11.
Daniel Schweizer Igor Vostiar Annabelle Heier Tim Serno Karin Schoenhammer Michael Jahn Stewart Jones Aline Piequet Christian Beerli Hermann Gram Achim Goepferich 《Journal of controlled release》2013
The sustained and localized delivery of monoclonal antibodies has become highly relevant, because of the increasing number of investigated local delivery applications in recent years. As the local delivery of antibodies is associated with high technological hurdles, very few successful approaches have been reported in the literature so far. Alginate-based delivery systems were previously described as promising sustained release formulations for monoclonal antibodies (mAbs). In order to further investigate their applicability, a single-dose animal study was conducted to compare the biocompatibility, the pharmacokinetics and the bioavailability of a human monoclonal antibody liquid formulation with two alginate-based sustained delivery systems after subcutaneous administration in rats. 28 days after injection, the depot systems were still found in the subcutis of the animals. A calcium cross-linked alginate formulation, which was injected as a hydrogel, was present as multiple compartments separated by subcutaneous tissue. An in situ forming alginate formulation was recovered as a single compact and cohesive structure. It can be assumed that the multiple compartments of the hydrogel formulation led to almost identical pharmacokinetic profiles for all tested animals, whereas the compact nature of the in situ forming system resulted in large interindividual variations in pharmacokinetics. As compared to the liquid formulation the hydrogel formulations led to lower mAb serum levels, and the in situ forming system to a shift in the time to reach the maximum mAb serum concentration (Tmax) from 2 to 4 days. Importantly, it was shown that after 28 days only marginal amounts of residual mAb were present in the alginate matrix and in the tissue at the injection site indicating nearly complete release. In line with this finding, systemic drug bioavailability was not affected by using the controlled release systems. This study successfully demonstrates the suitability and underlines the potential of polyanionic systems for local and controlled mAb delivery. 相似文献
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Ravel Jean-Marie Benkirane Mehdi Calmels Nadège Marelli Cecilia Ory-Magne Fabienne Ewenczyk Claire Halleb Yosra Tison François Lecocq Claire Pische Guillaume Casenave Philippe Chaussenot Annabelle Frismand Solène Tyvaert Louise Larrieu Lise Pointaux Morgane Drouot Nathalie Bossenmeyer-Pourié Carine Oussalah Abderrahim Guéant Jean-Louis Leheup Bruno Bonnet Céline Anheim Mathieu Tranchant Christine Lambert Laëtitia Chelly Jamel Koenig Michel Renaud Mathilde 《Journal of neurology》2021,268(5):1927-1937
Journal of Neurology - STUB1 has been first associated with autosomal recessive (SCAR16, MIM# 615768) and later with dominant forms of ataxia (SCA48, MIM# 618093). Pathogenic variations in STUB1... 相似文献
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Mark Rakobowchuk Emma Harris Annabelle Taylor Richard M. Cubbon Karen M. Birch 《European journal of applied physiology》2013,113(4):839-849
Traditional continuous aerobic exercise training attenuates age-related increases of arterial stiffness, however, training studies have not determined whether metabolic stress impacts these favourable effects. Twenty untrained healthy participants (n = 11 heavy metabolic stress interval training, n = 9 moderate metabolic stress interval training) completed 6 weeks of moderate or heavy intensity interval training matched for total work and exercise duration. Carotid artery stiffness, blood pressure contour analysis, and linear and non-linear heart rate variability were assessed before and following training. Overall, carotid arterial stiffness was reduced (p < 0.01), but metabolic stress-specific alterations were not apparent. There was a trend for increased absolute high-frequency (HF) power (p = 0.10) whereas both absolute low-frequency (LF) power (p = 0.05) and overall power (p = 0.02) were increased to a similar degree following both training programmes. Non-linear heart rate dynamics such as detrended fluctuation analysis $({| {1 - \alpha_{1} }|})$ also improved (p > 0.05). This study demonstrates the effectiveness of interval training at improving arterial stiffness and autonomic function, however, the metabolic stress was not a mediator of this effect. In addition, these changes were also independent of improvements in aerobic capacity, which were only induced by training that involved a high metabolic stress. 相似文献
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John W Kunstman Eric Kuo Annabelle L Fonseca Ronald R Salem 《HPB : the official journal of the International Hepato Pancreato Biliary Association》2014,16(11):987-993
Background
Post-operative pancreatic fistula (POPF) formation occurs frequently after a pancreaticoduodenectomy (PD). Recently, a 10-point Fistula Risk Score (FRS) evaluating the likelihood of clinically relevant POPF (CR-POPF) development has been described and validated. This scheme has yet to be evaluated in PD patients managed without intra-operative drain placement.Methods
Among patients undergoing PD at an academic centre since 2003, a retrospective analysis calculating FRS and its correlation with CR-POPF development was evaluated by logistic regression. Secondary analysis examined presentation and management of CR-POPF in undrained PD patients.Results
FRS was calculated for 265 patients; 97.7% were managed without operative drains. The overall incidence of CR-POPF was 7.9%. Logistic regression revealed a 1.6-fold increase in CR-POPF risk per 1-point increase in FRS [95% confidence interval (CI) 1.2–2.0]. The negative predictive value in patients with FRS <3 was 100%, whereas the positive predictive value of FRS >6 was 16.7%. The median time to CR-POPF diagnosis was 18 days [interquartile range (IQR) 13–23]; 70.0% required readmission and 10.0% required a laparotomy.Conclusions
Among patients without operative drainage, CR-POPF often has delayed presentations but most are managed non-operatively. The predictive value of high-risk FRS appears limited; conversely, a low-risk FRS accurately predicts the absence of CR-POPF and seems an appropriate metric for guiding care. 相似文献17.
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Dagmara Borzych-Duzalka Yelda Bilginer Il Soo Ha Mustafa Bak Lesley Rees Francisco Cano Reyner Loza Munarriz Annabelle Chua Silvia Pesle Sevinc Emre Agnieszka Urzykowska Lily Quiroz Javier Darío Ruscasso Colin White Lars Pape Virginia Ramela Nikoleta Printza Andrea Vogel Dafina Kuzmanovska Eva Simkova Dirk E. Müller-Wiefel Anja Sander Bradley A. Warady Franz Schaefer for the International Pediatric Peritoneal Dialysis Network Registry 《Journal of the American Society of Nephrology : JASN》2013,24(4):665-676
Little information exists regarding the efficacy, modifiers, and outcomes of anemia management in children with CKD or ESRD. We assessed practices, effectors, and outcomes of anemia management in 1394 pediatric patients undergoing peritoneal dialysis (PD) who were prospectively followed in 30 countries. We noted that 25% of patients had hemoglobin levels below target (<10 g/dl or <9.5 g/dl in children older or younger than 2 years, respectively), with significant regional variation; levels were highest in North America and Europe and lowest in Asia and Turkey. Low hemoglobin levels were associated with low urine output, low serum albumin, high parathyroid hormone, high ferritin, and the use of bioincompatible PD fluid. Erythropoiesis-stimulating agents (ESAs) were prescribed to 92% of patients, and neither the type of ESA nor the dosing interval appeared to affect efficacy. The weekly ESA dose inversely correlated with age when scaled to weight but did not correlate with age when normalized to body surface area. ESA sensitivity was positively associated with residual diuresis and serum albumin and inversely associated with serum parathyroid hormone and ferritin. The prevalence of hypertension and left ventricular hypertrophy increased with the degree of anemia. Patient survival was positively associated with achieved hemoglobin and serum albumin and was inversely associated with ESA dose. In conclusion, control of anemia in children receiving long-term PD varies by region. ESA requirements are independent of age when dose is scaled to body surface area, and ESA resistance is associated with inflammation, fluid retention, and hyperparathyroidism. Anemia and high ESA dose requirements independently predict mortality.Almost three decades after the advent of recombinant erythropoietin, the management of renal anemia has become a recent focus of attention and changing paradigms. Whereas correction of hemoglobin (Hb) levels to near-normal has previously been recommended on the basis of association studies linking more severe anemia to morbidity and mortality with dialysis,1–3 interventional clinical trials consistently demonstrate that near-normalization of Hb increases the risk of vascular events and mortality in adults receiving maintenance hemodialysis and in those with CKD who are not undergoing dialysis.4–6 This has prompted ongoing reevaluation and revisions of treatment targets in patients exposed to erythropoiesis-stimulating agents (ESAs).7The appropriateness of applying treatment recommendations established in adult hemodialysis populations at high cardiovascular risk and adults with CKD to children undergoing dialysis is questionable because cardiovascular events are far less common in children with CKD. Furthermore, two thirds of children requiring dialysis initially opt for peritoneal dialysis (PD), and there are no systematic studies in the adult PD population to inform the optimal Hb target range in these patients. The risk profile of patients receiving PD may differ from that of the hemodialysis setting because of the absence of dialysis-induced intermittent hemoconcentration and lack of contact activation of the complement and coagulation systems.Further aspects to consider in pediatric anemia management are the greater physical activity of children and the need for optimal cognitive functioning at school.8,9 The significant physiologic variation of the normal Hb range with age10 and the relative ESA sensitivity that reportedly increases with age during early childhood are also noteworthy.11The registry of the International Pediatric Peritoneal Dialysis Network (IPPN) prospectively collects detailed clinical, biochemical, dialysis, and medication-related information (including ESA types and doses and modalities of iron supplementation) from a substantial number of children undergoing long-term PD around the world. In-depth analysis of this unique database has allowed us to (1) gain insight into the demographic characteristics of renal anemia and its treatment in the pediatric PD population worldwide, (2) explore the relationship between ESA dose requirements and body dimensions, (3) identify factors contributing to ESA resistance in children, and (4) associate anemia control with patient outcomes. 相似文献
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Drennan V Davis K Goodman C Humphrey C Locke R Mark A Murray SF Traynor M 《Journal of advanced nursing》2007,60(5):459-469
AIM: This paper is a report of an integrative literature review to investigate: (a) the extent of entrepreneurial activity by nurses, midwives and health visitors in the United Kingdom and (b) the factors that influenced these activities. BACKGROUND: Internationally, social and commercial entrepreneurial activity is regarded as important for economic growth and social cohesion. METHODS: Seventeen bibliographic databases were searched using single and combined search terms: 'entrepreneur$', 'business', 'private practice', 'self-employ$', 'intrapreneur$'social enterprise$'mutuals', 'collectives', 'co-op' and 'social capital' which were related to a second layer of terms 'Nurs$', 'Midwi$', 'Visit$'. 'Entrepreneur$' Private Midwi$, Independent Midwi$, and 'nursing workforce'. In addition, hand searches of non-indexed journals and grey literature searches were completed. The following inclusion criteria were: (a) describing nurses, midwife and/or health visitor entrepreneurship (b) undertaken in the UK, and (c) reported between January 1996 and December 2005. RESULTS: Of 154 items included only three were empirical studies; the remainder were narrative accounts. While quality of these accounts cannot be verified, they provide as complete an account as possible in this under-researched area. The numbers of nurses, midwives and health visitors acting entrepreneurially were very small and mirror international evidence. A categorization of entrepreneurial activity was inductively constructed by employment status and product offered. 'Push' and 'pull' influencing factors varied between types of entrepreneurial activity. CONCLUSION: Empirical investigation into the extent to which nurses and midwives respond to calls for greater entrepreneurialism should take account of the complex interplay of contextual factors (e.g. healthcare legislation), professional and managerial experience and demographic factors. 相似文献