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21.
Garnero P Landewé R Boers M Verhoeven A Van Der Linden S Christgau S Van Der Heijde D Boonen A Geusens P 《Arthritis and rheumatism》2002,46(11):2847-2856
OBJECTIVE: The known risk factors for radiologic progression in rheumatoid arthritis (RA) are not optimally discriminative in patients with early disease who do not have evidence of radiologic damage. We sought to determine whether urinary C-terminal crosslinking telopeptide of type I (CTX-I) and type II (CTX-II) collagen (markers of bone and cartilage destruction, respectively) are associated with long-term radiologic progression in patients with early RA. METHODS: This was a prospective study of 110 patients with early RA who were participating in the COBRA (Combinatietherapie Bij Reumato?de Artritis) clinical trial and followup study, a randomized controlled trial comparing the efficacy of oral pulse prednisolone, methotrexate, plus sulfasalazine with sulfasalazine alone. We investigated the relationship between baseline levels of urinary CTX-I and CTX-II and the mean annual progression of joint destruction over a median of 4 years, as measured by changes in the modified Sharp score (average of 2 independent readers). RESULTS: In multivariate logistic regression analysis, baseline urinary CTX-I and CTX-II levels in the highest tertile were the strongest predictors of radiologic progression (Sharp score increase >2 units/year; odds ratio 7.9 and 11.2, respectively), independently of treatment group, erythrocyte sedimentation rate (ESR), Disease Activity Score in 28 joints, rheumatoid factor (RF), and baseline joint damage (Sharp score). The likelihood ratios for a positive test were 3.8 and 8.0 for CTX-I and CTX-II, respectively, which compared favorably with the likelihood ratios for the ESR (3.0), baseline joint damage (1.6), and RF (1.8). When patients were grouped according to the presence (Sharp score >/=4, n = 49) and absence (Sharp score <4, n = 61) of joint damage at baseline, CTX-I and CTX-II levels were predictive only in those without baseline joint damage (odds ratio 14.9 and 25.7, respectively). CONCLUSION: High baseline levels of urinary CTX-I and CTX-II independently predict an increased risk of radiologic progression over 4 years in patients with early RA, especially those without radiologic joint damage. Urinary CTX-I and CTX-II may be useful for identifying individual RA patients at high risk of progression very early in the disease, before erosions can be detected radiographically. Such patients may be in special need of treatments that inhibit bone and cartilage degradation. 相似文献
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Wessel Ganzevoort Annelies Rep Gouke J Bonsel Johanna I P de Vries Hans Wolf 《Journal of hypertension》2004,22(7):1235-1242
BACKGROUND: Pre-eclampsia is a multisystem disorder, peculiar to and frequent in human pregnancy. It remains a leading cause of maternal and neonatal morbidity and mortality. Hemodynamic disturbances are the most prominent features of the syndrome. PURPOSE: To provide an overview of plasma volume regulation and blood pressure control mechanisms outside pregnancy, and of the changes in normal pregnancies and in pregnancies complicated by hypertensive disorders. Furthermore, to discuss the rationale of several hemodynamic interventions. RESULTS: In normal pregnancy, large cardiovascular changes take place. A generalized fall in vascular tone by systemic vasorelaxation causes increased blood volume, heart rate and cardiac output. In the preclinical phase, differences have been observed between normal and hypertensive pregnancies in the function of the autonomic nervous system, cardiac output and plasma volume, the volume remaining at the non-pregnant level. In the clinical phase of pre-eclampsia the typical case picture is one of a vasoconstrictive state with low plasma volume and cardiac output, high blood pressure and systemic vascular resistance in combination with signs of organ damage [proteinuria, hemolysis elevated liver enzymes low platelets (HELLP) syndrome]. Hemodynamic management is necessary in severe disease to prevent maternal complications. Management primarily focuses on pharmacological treatment of blood pressure. Clinicians make educated choices from a limited array of available drugs: beta-receptor antagonists, nifedipine, dihydralazine, methyldopa or ketanserine. Other drugs have restricted use in pregnancy. Management of low circulating volume with plasma expanders remains a subject of controversy. 相似文献
23.
Peter Blanckaert Annelies Cannaert Katleen Van Uytfanghe Fabian Hulpia Eric Deconinck Serge Van Calenbergh Christophe Stove 《Drug testing and analysis》2020,12(4):422-430
This paper reports on the identification and full chemical characterization of isotonitazene (N,N‐diethyl‐2‐[5‐nitro‐2‐({4‐[(propan‐2‐yl)oxy]phenyl}methyl)‐1H‐benzimidazol‐1‐yl]ethan‐1‐amine), a potent NPS opioid and the first member of the benzimidazole class of compounds to be available on online markets. Interestingly, this compound was sold under the name etonitazene, a structural analog. Identification of isotonitazene was performed by gas chromatography mass spectrometry (GC–MS) and liquid chromatography time‐of‐flight mass spectrometry (LC‐QTOF‐MS), the latter identifying an exact‐mass m/z value of 411.2398. All chromatographic data indicated the presence of a single, highly pure compound. Confirmation of the specific benzimidazole regio‐isomer was performed using 1H and 13C NMR spectroscopy, after which the chemical characterization was finalized by recording Fourier‐transform (FT‐IR) spectra. A live cell‐based reporter assay to assess the in vitro biological activity at the μ‐opioid receptor (MOR) revealed that isotonitazene has a high potency (EC50 of 11.1 nM) and efficacy (Emax 180% of that of hydromorphone), thus confirming that this substance is a strong opioid. Isotonitazene has not been previously detected, either in powder form, or in biological fluids. The high potency and efficacy of isotonitazene, combined with the fact that this compound was being sold undiluted, represents an imminent danger to anyone aiming to use this powder. 相似文献
24.
Vugteveen Jorien de Bildt Annelies Hartman Catharina A. Reijneveld Sijmen A. Timmerman Marieke E. 《European child & adolescent psychiatry》2021,30(12):1983-1994
European Child & Adolescent Psychiatry - The Strengths and Difficulties Questionnaire (SDQ) is widely used, based on evidence of its value for screening. This evidence primarily regards the... 相似文献
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Gitta Bleeker Berthe L. van Eck-Smit Koos H. Zwinderman Rogier Versteeg Max M. van Noesel Boen L. Kam Gertjan J. Kaspers Annelies van Schie Susan G. Kreissman Gregory Yanik Barbara Hero Matthias Schmidt Geneviève Laureys Bieke Lambert Ingrid Øra Johannes H. Schulte Huib N. Caron Godelieve A. Tytgat 《European journal of nuclear medicine and molecular imaging》2015,42(2):222-230
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Carolina Noble Annelies Cannaert Kristian Linnet Christophe P. Stove 《Drug testing and analysis》2019,11(3):501-511
Synthetic cannabinoids (SCs) are the most chemically diverse group of new psychoactive substances. This group has been associated with several intoxications, many with fatal outcomes. Although advancements have been achieved in pharmacology, metabolism, and detection of these compounds in recent years, these aspects are still unresolved for many SCs. The aim of this study was to investigate the in vitro potency of 14 indole‐ and indazole‐based SCs by applying a stable CB1 or CB2 receptor activation assay and correlating the activity with their structure. The half‐maximal effective concentration (EC50) of 5‐chloropentyl, 5‐bromopentyl, and 5‐iodopentyl JWH‐122 analogs varied from 74.1 to 283.7 nM for CB1 and 7.05 to 23.4 nM for CB2, where the addition of a chlorine atom enhanced the potency at CB1 compared with the bromo and iodo analogs. AM‐2201 was the most active at CB1 within this naphthoylindole family, with an EC50 of 23.5 nM but with the lowest efficacy (Emax 98.8%). Within the indole‐3‐carboxamide derivatives, 5F‐MDMB‐PICA was the most active compound, with a CB1/CB2 EC50 of 3.26/0.87 nM and an Emax around three times higher than JWH‐018. ADB‐FUBINACA was the most potent tested SC overall, with a CB1/CB2 EC50 of 0.69/0.59 nM, and an Emax around 3‐fold higher than that for JWH‐018 at CB1. The data obtained in this study confirm how small differences in the structure of SCs might lead to large differences in their activity, especially at CB1, which may be correlated with differences in their toxic effects in humans. 相似文献