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排序方式: 共有769条查询结果,搜索用时 187 毫秒
1.
Feike J. Loots Daan Smulders Paul Giesen Rogier M. Hopstaken Marleen Smits 《The European journal of general practice》2021,27(1):83
BackgroundSigns of the systemic inflammatory response syndrome (SIRS) – fever (or hypothermia), tachycardia and tachypnoea – are used in the hospital setting to identify patients with possible sepsis.ObjectivesTo determine how frequently abnormalities in the vital signs of SIRS are present in adult out-of-hours (OOH) primary care patients with suspected infections and assess the association with acute hospital referral.MethodsWe conducted a cross-sectional study at the OOH GP cooperative in Nijmegen, the Netherlands, between August and October 2015. GPs were instructed to record the body temperature, heart rate and respiratory rate of all patients with suspected acute infections. Vital signs of SIRS, other relevant signs and symptoms, and referral state were extracted from the electronic registration system of the OOH GP cooperative retrospectively. Logistic regression analysis was used to evaluate the association between clinical signs and hospital referral.ResultsA total of 558 patients with suspected infections were included. At least two SIRS vital signs were abnormal in 35/409 (8.6%) of the clinic consultations and 60/149 (40.3%) of the home visits. Referral rate increased from 13% when no SIRS vital sign was abnormal to 68% when all three SIRS vital signs were abnormal. Independent associations for referral were found for decreased oxygen saturation, hypotension and rapid illness progression, but not for individual SIRS vital signs.ConclusionAlthough patients with abnormal vital signs of SIRS were referred more often, decreased oxygen saturation, hypotension and rapid illness progression seem to be most important for GPs to guide further management. 相似文献
2.
Corine C Visser Sanja Stevanovi? L Heleen Voorwinden Louis van Bloois Pieter J Gaillard Meindert Danhof Daan J A Crommelin Albertus G de Boer 《European journal of pharmaceutical sciences》2005,25(2-3):299-305
In this study, we aim to target pegylated liposomes loaded with horseradish peroxidase (HRP) and tagged with transferrin (Tf) to the BBB in vitro. Liposomes were prepared with the post-insertion technique: micelles of polyethylene glycol (PEG) and PEG-Tf were inserted into pre-formed liposomes containing HRP. Tf was measured indirectly by measuring iron via atomic absorption spectroscopy. All liposomes were around 100 nm in diameter, contained 5-13 microg HRP per mumol phospholipid and 63-74 Tf molecules per liposome (lipo Tf) or no Tf (lipo C). Brain capillary endothelial cells (BCEC) were incubated with liposomes at 4 degrees C (to determine binding) or at 37 degrees C (to determine association, i.e. binding+endocytosis) and the HRP activity, rather than the HRP amount was determined in cell lysates. Association of lipo Tf was two- to three-fold higher than association of lipo C. Surprisingly, the binding of lipo Tf at 4 degrees C was four-fold higher than the association of at 37 degrees C. Most likely this high binding and low endocytosis is explained by intracellular degradation of endocytosed HRP. In conclusion, we have shown targeting of liposomes loaded with protein or peptide drugs to the BCEC and more specifically to the lysosomes. This is an advantage for the treatment of lysosomal storage disease. However, drug targeting to other intracellular targets also results in intracellular degradation of the drug. Our experiments suggest that liposomes release some of their content within the BBB, making targeting of liposomes to the TfR on BCEC an attractive approach for brain drug delivery. 相似文献
3.
Daan P Livestro Alona Muzikansky Emily M Kaine Thomas J Flotte Arthur J Sober Martin C Mihm James S Michaelson A Benedict Cosimi Kenneth K Tanabe 《Journal of clinical oncology》2005,23(27):6739-6746
PURPOSE: Previous studies have established that patients with desmoplastic melanoma (DM) have thicker primary tumors. Consequently, comparisons with other forms of melanoma have been strongly biased by differences in Breslow stage. This is the first case-matched control study comparing DM with other forms of melanoma. PATIENTS AND METHODS: From a database of 3,202 melanoma patients treated at one institution, 89 patients with DM and 178 case-matched control patients (2:1) were identified by matching for tumor thickness, age, sex, and year of diagnosis. Clinical, pathologic, and outcome information was obtained from chart review. RESULTS: Controls were matched successfully to patients for tumor thickness, age, sex, and year of diagnosis. Presentation with American Joint Committee on Cancer stage III or IV disease is less common in patients with DM compared to case-matched control patients (5% v 21%; P < .001). Re-excisions to obtain clear surgical margins are required more often in patients with DM compared to case-matched control patients (21% v 6%; P < .001). Risk of positive sentinel nodes is lower in patients with DM compared to case-matched control patients (8% v 34%; P = .013). Despite these differences, survival rates of patients with DM are the same as case-matched control patients. CONCLUSION: Use of case-matched control patients matched for tumor thickness avoids biases introduced by the advanced Breslow stage of DMs. DMs are more locally aggressive than thickness-matched controls, and positive sentinel nodes are limited to patients with thick primary tumors. Importantly, patients with DM have survival rates similar to patients with other melanomas of similar thickness. 相似文献
4.
Immunogenicity of meningococcal PorA formulations encapsulated in biodegradable microspheres. 总被引:1,自引:0,他引:1
Carmen Arigita Joost van den Berg Karin Wensink Mies van Steenbergen Wim E Hennink Daan J A Crommelin Gideon F A Kersten Wim Jiskoot 《European journal of pharmaceutical sciences》2004,21(2-3):131-141
The purpose of our study was to investigate the possibility to microencapsulate liposomes and meningococcal outer membrane vesicles (OMV), both containing neisserial pore protein A (PorA), in biodegradable dextran- and mannan-based microspheres and to study the immunogenicity of the encapsulated PorA formulations. PorA-liposomes and OMV were encapsulated in dextran- or mannan-based microspheres by using an aqueous two-phase system consisting of a polyethylene glycol solution and a methacrylated dextran or mannan solution. The formulations were characterized for size distribution, PorA structure and antigen recovery after release. Calcein-containing model liposomes were used to establish the encapsulation efficiency and release profiles from both types of microspheres. The immunogenicity of the PorA-containing formulations was determined in mice after subcutaneous immunization. Liposomes were encapsulated in dextran and mannan microspheres with a high efficiency (70-90%). Calcein liposomes, after a 5-day lag period, exhibited apparent zero-order release kinetics from both types of microspheres between Days 5 and 10 of incubation in vitro. The total release was 80 and 100% from mannan and dextran microspheres, respectively. The trimeric PorA conformation was preserved in the released liposomes and OMV and the antigen was partly recovered. The immunogenicity of PorA-liposomes and OMV encapsulated in dextran or mannan microspheres was preserved. In conclusion, PorA-liposomes and OMV could be encapsulated in dextran- and mannan-based microspheres with high efficiency. The immunogenicity of encapsulated antigen was preserved. 相似文献
5.
Daan J. aan de Kerk Ester M.M. van Leeuwen Machiel H. Jansen J. Merlijn van den Berg Marielle Alders Clementine L. Vermont René A.W. van Lier Steven T. Pals Taco W. Kuijpers 《Clinical immunology (Orlando, Fla.)》2013,149(1):25-31
Mutations in the DOCK8 gene define the most common form of autosomal-recessive Hyper-IgE-syndrome (AR-HIES/OMIM#243700). In a patient with extensive molluscum contagiosum lesions, a homozygous DOCK8 gene deletion was demonstrated. 相似文献
6.
Corine C. Visser L. Heleen Voorwinden Liesbeth R. Harders Mohamed Eloualid Louis van Bloois Daan J.A. Crommelin 《Journal of drug targeting》2013,21(9-10):569-573
Liposomes for drug delivery are often prepared with maleimide groups on the distal end of PEG to enable coupling of homing devices, such as antibodies, or other proteins. EDTA is used to stabilize the thiol group in the homing device for attachment to the maleimide. However, when using a homing device that contains a metal, EDTA inactivates this by scavenging of the metal. Holo-transferrin (Tf) containing two iron atoms (Fe3+), has a much higher affinity for the Tf receptor than apo-Tf (which does not contain any Fe3+). To couple Tf to a liposome, the introduction of a thiol group is necessary. During this process, by using N-succinimidyl S-acetylthioacetate (SATA), followed by 2–3 h coupling to the liposomes, Fe3+ is scavenged by EDTA. This causes a decreased affinity of Tf for its receptor, resulting in a decreased targeting efficiency of the liposomes.Tris(2-carboxyethyl)phosphine (TCEP) hydrochloride is a sulfhydryl reductant that is often used in protein biochemistry. We found that TCEP (0.01 mM) does not scavenge Fe3+ from Tf and is able to protect thiol groups for the coupling to maleimide. Furthermore, TCEP does not interfere with the maleimide coupling itself.In this communication, we describe the preparation of liposomes, focussing on the coupling of Tf to the maleimide linker at the distal end of PEG, without loosing Fe3+ from Tf. This method can be applied to other metal-containing homing devices as well. 相似文献
7.
Gleason grade 4 prostate adenocarcinoma patterns: an interobserver agreement study among genitourinary pathologists 下载免费PDF全文
Charlotte F Kweldam Daan Nieboer Ferran Algaba Mahul B Amin Dan M Berney Athanase Billis David G Bostwick Lukas Bubendorf Liang Cheng Eva Compérat Brett Delahunt Lars Egevad Andrew J Evans Donna E Hansel Peter A Humphrey Glen Kristiansen Theodorus H van der Kwast Cristina Magi‐Galluzzi Rodolfo Montironi George J Netto Hemamali Samaratunga John R Srigley Puay H Tan Murali Varma Ming Zhou Geert J L H van Leenders 《Histopathology》2016,69(3):441-449
8.
9.
Guy Laureys Barbara Willekens Ludo Vanopdenbosch Olivier Deryck Dominik Selleslag Miguel D’Haeseleer Ann De Becker Bénédicte Dubois Daan Dierickx Gaetano Perrotta Virginie De Wilde Vincent van Pesch Nicole Straetmans Dominique Dive Yves Beguin Bart Van Wijmeersch Koen Theunissen Tessa Kerre Ann Van de Velde 《Acta neurologica Belgica》2018,118(2):161-168
Multiple sclerosis is considered to be an immune mediated inflammatory disorder of the central nervous system. It mainly affects young, socioeconomic active patients. Although our armamentarium for this disease has significantly evolved in recent years some patients remain refractory to conventional therapies. In these cases, autologous hematopoietic stem cell transplantation can be considered as a therapeutic option. Decreasing morbidity, mortality, and increasing patient awareness have led to rising inquiry by our patients about this treatment option. With the aim of a standardized protocol and data registration, a Belgian working party on stem cell therapy in multiple sclerosis was established. In this paper, we report the consensus protocol of this working party on autologous hematopoietic stem cell transplantation in multiple sclerosis. 相似文献
10.
Daan J. A. Crommelin Jon S. B. de Vlieger Vera Weinstein Stefan Mühlebach Vinod P. Shah Huub Schellekens 《The AAPS journal》2014,16(1):11-14
In the last decade, discussions on the development of the regulatory framework of generic versions of complex drugs such as biologicals and non-biological complex drugs have attracted broad attention. The terminology used is far from harmonized and can lead to multiple interpretations of legal texts, reflection papers, and guidance documents regarding market introduction as well as reimbursement. This article describes the meaning of relevant terms in different global regions (Europe, USA, WHO) and offers a proposal for a globally accepted terminology regarding (non-) biological complex drugs. 相似文献