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11.
This is a case report of a male with infection in the right knee joint progressing to sepsis. However, the patient initially complained mainly of dysarthria and breathlessness. He rapidly developed respiratory insufficiency with the loss of consciousness. Echocardiography revealed severe dysfunction of the left ventricle, suggesting acute failure of the chronically failing heart. The patient was referred to a coronary care unit. Only the further course of the disease, particularly progression of the local finding on the right leg and development of fever, together with significantly elevated inflammatory parameters in laboratory findings, resulted in the diagnosis of sepsis which also included myocardial dysfunction and brain hypoperfusion manifested as dysarthria. 相似文献
12.
Radovan Vasko Gerhard A. Müller Brian B. Ratliff Klaus Jung Sarah Gauczinski Michael J. Koziolek 《Clinical and experimental nephrology》2013,17(4):563-568
Background
The assessment of hydration status remains a challenging task in hemodialysis (HD) management. There are only limited data available on the relevance of clinical decisions in the estimation of dialysis overhydration (OH). The objective of this study was to examine the significance of clinical judgment in the assessment of pre-dialysis OH.Methods
We compared the performance of three methods of OH assessment: (1) clinical judgment guided by a single clinical examination with (2) multifrequency bioimpedance analysis (BIA) and (3) complex systematic clinical approach. We additionally studied the associations of these methods with selected laboratory and imaging parameters.Results
Any of the single parameters alone reached a sufficient level of accuracy for reliable prediction of OH. Clinical judgment was the single most important factor in OH estimation, and also had the highest contribution when in combination with other parameters. BIA reliably measured extracellular fluid, but the automatically calculated OHBIA exhibited a substantial degree of inaccuracy that precludes the use of BIA as a standard at present. The combination of clinical judgment with additional clinical parameters had the highest prediction accuracy for OH. Among the parameters studied, vena cava collapsibility index and calf circumference showed the strongest association with OH. Echocardiography, cardiothoracic index, atrial natriuretic peptide levels and spirometry did not have acceptable sensitivity.Conclusion
The systematic clinical approach combining physician and patient inputs, laboratory and imaging data enables an individualized decision and a superior accuracy in OH assessment. 相似文献13.
François Perreault Silvia Pedroso Melegari Cristiane Funghetto Fuzinatto Nicoleta Bogdan Mario Morin Radovan Popovic William Gerson Matias 《Environmental toxicology》2014,29(3):328-336
Polyamidoamine (PAMAM) dendrimers are used for many pharmaceutical and biomedical applications. However, the toxicological risks of several PAMAM‐based compounds are still not fully evaluated, despite evidences of PAMAM deleterious effects on biological membranes, leading to toxicity. In this report, we investigated the toxicity of generation 0 PAMAM‐coated gold nanoparticles (AuG0 NPs) in four different models to determine how different cellular systems are affected by PAMAM‐coated NPs. Toxicity was evaluated in two mammalian cell lines, Neuro 2A and Vero, in the green alga Chlamydomonas reinhardtii and the bacteria Vibrio fischeri. AuG0 NP treatments reduced cell metabolic activity in algal and bacterial cells, measured by esterase enzymatic activity (C. reinhardtii) and luminescence emission (V. fischeri). EC50 value after 30 min of treatment was similar in both organisms, with 0.114 and 0.167 mg mL?1 for C. reinhardtii and V. fischeri, respectively. On the other hand, AuG0 NPs induced no change of mitochondrial activity in mammalian cells after 24 h of treatment to up to 0.4 mg mL?1 AuG0 NPs. Change in the absorption spectra of AuG0 NP in the mammalian cell culture media may indicate an alteration of NP properties that contributed to the low toxicity of AuG0 NPs in mammalian cells. For a safe development of PAMAM‐based nanomaterials, the difference of sensitivity between mammalian and microbial cells, as well as the modulation of NPs toxicity by medium properties, should be taken into account when designing PAMAM NPs for applications that may lead to their introduction in the environment. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 328–336, 2014. 相似文献
14.
Balaji Bharatwaj Radovan Dimovski Denise S. Conti Sandro R. P. da Rocha 《The AAPS journal》2014,16(3):522-538
The purpose of this study was to (a) Determine the cellular transport and uptake of amine-terminated generation 3 (G3) poly(amido amine) (PAMAM) dendrimers across an in vitro model of the pulmonary epithelium, and the ability to modulate their transport by forming nanoblends of the dendrimers with biodegradable solid polymeric nanoparticles (NPs) and (b) to formulate dendrimer nanocarriers in portable oral inhalation devices and evaluate their aerosol characteristics. To that end, fluorescein isothiocyanate (FITC)-labeled G3 PAMAM dendrimer nanocarriers (DNCs) were synthesized, and also encapsulated within poly lactide-co-glycolide nanoparticles (NPs). Transport and uptake of both DNCs encapsulated within NPs (nanoblends) and unencapsulated DNCs were tracked across polarized monolayers of airway epithelial cells, Calu-3. DNCs were also formulated as core-shell microparticles in pressurized metered-dose inhalers (pMDIs) and their aerodynamic properties evaluated by Andersen cascade impaction. The apparent permeability of DNCs across the airway epithelial model was similar to that of a paracellular marker of comparable molar mass—order of 10−7 cm s−1. The transport and cellular internalization of the DNCs can be modulated by formulating them as nanoblends. The transport of the DNCs across the lung epithelium was completely suppressed within the time of the experiment (5 h) when formulated as blends. The encapsulation also prevents saturation of the cellular internalization profile. Nanoblending may be a potential strategy to modulate the rate of transport and cellular uptake of DNCs, and thus be used as a design strategy to achieve enhanced local or systemic drug delivery.
Electronic supplementary material
The online version of this article (doi:10.1208/s12248-014-9588-5) contains supplementary material, which is available to authorized users.KEY WORDS: Calu-3, dendrimers, nanoparticles, nanoblends, oral inhalation, pressurized metered-dose inhalers, transport modulation 相似文献15.
Frédéric Baron Fabio Efficace Laura Cannella Petra Muus Silvia Trisolini Constantijn J. M. Halkes Paola Fazi Marco Vignetti Jean-Pierre Marie Patrizia Chiusolo Walter van der Velden Edoardo La Sala Umberto Vitolo Xavier Thomas Francois Lefrère Sr. Francesco Di Raimondo Jean-Henri Bourhis Giorgina Specchia José E. Guimarães Bernardino Allione Radovan Vrhovac Felicetto Ferrara Marian Stevens-Kroef Liv Meert Theo de Witte Roelof Willemze Sergio Amadori Stefan Suciu 《American journal of hematology》2020,95(7):749-758
We provide a long-term evaluation of patients enrolled in the EORTC/GIMEMA AML-10 trial which included a total of 2157 patients, 15-60 years old, randomized to receive either daunorubicin (DNR, 50 mg/m2), mitoxantrone (MXR, 12 mg/m2), or idarubicin (IDA, 10 mg/m2) in addition to standard-dose cytarabine and etoposide for induction chemotherapy and intermediate dose cytarabine for consolidation. Younger patients who reached complete remission with complete (CR) or incomplete (CRi) recovery were then scheduled to receive an allogeneic hematopoietic stem cell transplantation (HSCT). That was if they had a HLA-identical sibling donor; in all other cases, an autologous HSCT had to be administered. At an 11-year median follow-up, the 5-year, 10-year and 15-year overall survival (OS) rates were 33.2%, 30.1% and 28.0%, respectively. No significant difference between the three randomized groups regarding OS was observed (P = .38). In young patients, 15-45 years old, no treatment difference (P = .89) regarding OS was observed, while in patients 46-60 years old, MXR and IDA groups had a trend for a longer OS as compared to the DNR group (P = .029). Among younger patients without a favorable MRC cytogenetic risk subgroup who achieved a CR/CRi after induction chemotherapy, those with a HLA-identical sibling donor had higher 10-year and 15-year OS rates than those without. In older patients who reached CR/CRi, the long-term outcomes of those with or without a donor was similar. In conclusion, long-term outcomes of the study confirmed similar OS in the three randomized groups in the whole cohort of patients. 相似文献
16.
By simple reactions involving various cobalt(II) carboxylates (acetate and in situ prepared pivalate and 4-hydroxybenzoate salts) and neocuproine (neo), we were able to prepare three different carboxylate complexes with the general formula [Co(neo)(RCOO)2] (R = –CH3 for 1, (CH3)3C– for 2, and 4OH-C4H6– for 3). The [Co(neo)(RCOO)2] molecules in the crystal structures of 1–3 adopt a rather distorted coordination environment, with the largest trigonal distortion observed for 1, whereas 2 and 3 are similarly distorted from ideal octahedral geometry. The combined theoretical and experimental investigations of magnetic properties revealed that the spin Hamiltonian formalism was not a valid approach and the L-S Hamiltonian had to be used to reveal very large magnetic anisotropies for 1–3. The measurements of AC susceptibility showed that all three compounds exhibited slow-relaxation of magnetization in a weak external static magnetic field, and thus can be classified as field-induced single-ion magnets. It is noteworthy that 1 also exhibits a weak AC signal in a zero-external magnetic field. 相似文献
17.
Lucić Vrdoljak A Bradamante V Radić B Peraica M Fuchs R Reiner Z 《Acta pharmaceutica (Zagreb, Croatia)》2005,55(2):177-185
The paper describes the effect of glucocorticoid dexamethasone (DM) given intraperitoneally on the catalytic activity of butyrylcholinesterase (BuChE) measured in plasma, liver and white adipose tissue of rats of both sexes. Effects of DM on the concentration of plasma lipids and lipoproteins were also tested. Rats were given multiple (2 and 4) pharmacological doses (0.4 and 3.0 mg kg(-1) body mass) of DM. All animals were sacrificed 48 hours after the last dose. Administration of DM significantly decreased the catalytic activity of BuChE in plasma and liver of all treated groups regardless of sex. BuChE catalytic activity in white adipose tissue differed depending on the dose and frequency of administration. In contrast to liver where both doses caused significant BuChE inhibition, the lower DM dose did not inhibit BuChE activity in adipose tissue, and the inhibition achieved by the higher dose was not as strong as in liver. This result corroborates an earlier hypothesis that BuChE is also synthesized in the adipose tissue. DM significantly increased plasma concentrations of triglycerides, total cholesterol and high-density lipoprotein (HDL) cholesterol and decreased the low-density lipoprotein (LDL) cholesterol concentration. Neither positive correlation between BuChE and triglycerides nor negative correlation between BuChE and HDL was found. Changes in lipid profile during DM treatment were not sex- and time-dependent. 相似文献
18.
The antifibrotic effects of relaxin in human renal fibroblasts are mediated in part by inhibition of the Smad2 pathway 总被引:6,自引:0,他引:6
Heeg MH Koziolek MJ Vasko R Schaefer L Sharma K Müller GA Strutz F 《Kidney international》2005,68(1):96-109
BACKGROUND: The peptide hormone relaxin has been demonstrated to exert antifibrotic effects in renal and extrarenal tissues. The aims of this study were to identify potential anti-fibrotic effects of relaxin on human renal fibroblasts in vitro and to analyze their mechanisms. METHODS: All experiments were performed in established renal fibroblast cell lines and in primary cortical fibroblasts. Effects of relaxin were analyzed on cell proliferation, apoptosis, activation of renal fibroblasts, synthesis and secretion of collagen type I and fibronectin, as well as on the secretion of matrix metalloproteinases (MMPs). Effects on transforming growth factor-beta1 (TGF-beta1) receptor binding were analyzed by flow cytometry and on TGF-beta1 signal transduction by immunoblot analyses for Smad4 and 7, translocation from cytosol to nucleus for Smad2 and 3 as well as for phosphorylated and unphosphorylated forms of p38, c-Jun NH2 terminal kinase (JNK) and extracellular-regulated protein kinase (ERK). Finally, specific siRNAs for Smad2 and 3 were applied to assess the signal transduction pathway. RESULTS: After stimulation with relaxin, tyrosine phosphorylation of a 220 kD protein was demonstrated, indicating interaction with the receptor. Relaxin had only modest inhibitory effects on cell proliferation, and no effects on apoptosis. Conversely, relaxin exerted robust effects on TGF-beta1-induced fibroblast to myofibroblast transformation as well as on matrix synthesis and secretion even at the smallest dose tested. The secretion of MMP-2 and MMP-9 was induced noticeably by all investigated relaxin concentrations. TGF-beta1 receptor binding was not influenced by relaxin; however, it prevented Smad2 phosphorylation, translocation to nucleus, and complex formation between Smad2 and 3 indicating a possible interaction with TGF-beta1 signaling. These findings were corroborated by studies using siRNAs to Smad2 and 3 where siRNA to Smad2 but not to Smad3 inhibited the TGF-beta1 induction of fibronectin synthesis. There was no influence of relaxin on intracellular Smad3, Smad4, and Smad7 translocation or phosphorylation of mitogen-activated protein (MAP) kinases. CONCLUSION: Relaxin is a potent inhibitor of TGF-beta1-induced extracellular matrix (ECM) synthesis and secretion as well as fibroblast activation. Furthermore, it induces ECM degradation by induction of MMP-2 and MMP-9. These effects are mediated, at least in part, by inhibition of TGF-beta1 signaling. 相似文献
19.
Cardiac troponin T (cTnT) in hemodialysis patients with asymptomatic and symptomatic atherosclerosis
BACKGROUND: Cardiovascular mortality is higher in hemodialysis (HD) patients than in the general population. Cardiac troponin T (cTnT) is established as a sensitive marker of myocardial injury in the general population. Less is known about the association between cTnT and intima-media thickness (IMT) and presence of plaques in carotid arteries (asymptomatic atherosclerosis) and prognostic value of cTnT for cardiovascular mortality (symptomatic atherosclerosis) in HD patients. METHODS: In our study 90 HD patients (mean age 56.2 +/- 13.3 years) were followed after determination of cTnT level. Outcome after 21 months was chosen as the end point. In 52 randomly selected HD patients, IMT was measured with B-mode ultrasonography. Plaque occurrence and their numbers were also determined. RESULTS: In 24 (26.6%) patients, cTnT values were >0.1 microg/L (positive test for myocardial injury). During follow-up, 13 patients died from cardiovascular causes and their cTnT values were significantly higher (0.12 vs. 0.06 microg/L; p <0.001) than in those who survived. Correlation between cardiovascular mortality and cTnT was found (p <0.001). The cut-off level of 0.1 microg/L resulted in survival rates of 92% and 64% (p=0.0006). The IMT values of carotid artery were significantly higher (0.85 vs. 0.70 mm; p <0.011) in patients with elevated cTnT. All patients with elevated cTnT had plaques and the number of plaques was significantly higher in these patients (p <0.0001). CONCLUSIONS: cTnT was frequently elevated in our HD patients and was associated with higher cardiovascular mortality and a predictor of cardiovascular outcome. Patients with elevated cTnT showed advanced asymptomatic atherosclerosis in carotid arteries. 相似文献
20.
Psychopathology and treatment responsiveness of patients with first-episode schizophrenia 总被引:1,自引:1,他引:0 下载免费PDF全文
Cesková E Prikryl R Kaspárek T Ondrusová M 《Neuropsychiatric Disease and Treatment》2005,1(2):179-185
One hundred and four male patients hospitalized for the first time with the diagnosis of first-episode schizophrenia were comprehensively assessed on admission and discharge. Psychopathology, treatment response, and remission rates were evaluated (based on the Positive and Negative Syndrome Scale (PANSS), severity of symptoms only). On admission, the most frequently observed symptoms were lack of judgment and insight (87.6%), suspiciousness/feelings of persecution (82.3%), delusions (77%), poor attention (70%), disturbance of volition (65.4%), conceptual disorganization (64.7%), and active social avoidance (64%). Except for delusions and hallucinations, the positive items of the PANSS correlated significantly with negative symptoms, and conceptual disorganization correlated with the greatest number of negative symptoms. Individual negative symptoms were present in about half the patients. At discharge, the most frequent symptoms were again lack of judgment and insight (in 55.7%), and for negative symptoms they were blunted affect (22.1%), emotional withdrawal (21.2%), and passive/apathetic social withdrawal (19.5%). The positive symptoms of suspiciousness/feelings of persecution and grandiosity persisted in 20.6% of patients. On average, all symptoms were significantly reduced 44 days after admission. The negative symptoms improved less, compared with the positive ones. At discharge there was a high rate of responders (response defined as minimal 30% reduction of total PANSS): 73% and 74% of patients fulfilled the criteria for remission. On admission, the responders (n = 76) had significantly higher scores of most symptoms, both positive and negative ones than nonresponders (n = 28). 相似文献