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21.
A strategy to improve treatment‐related mortality and abandonment of therapy for childhood ALL in a developing country reveals the impact of treatment delays 下载免费PDF全文
Amaranto Suarez MD Martha Piña MD Diana X. Nichols‐Vinueza MD John Lopera MD Lyda Rengifo MD Mauricio Mesa MD Marcela Cardenas RN Lisa Morrissey RN Galo Veintemilla MD Martha Vizcaino MD Ligia Del Toro MD Victor Vicuna PhD Jorge Fernandez LICSW Donna Neuberg ScD Kristen Stevenson MS Alejandro Gutierrez MD 《Pediatric blood & cancer》2015,62(8):1395-1402
Background
Treatment‐related mortality and abandonment of therapy are major barriers to successful treatment of childhood acute lymphoblastic leukemia (ALL) in the developing world.Procedure
A collaboration was undertaken between Instituto Nacional de Cancerologia (Bogota, Colombia), which serves a poor patient population in an upper‐middle income country, and Dana‐Farber/Boston Children's Cancer and Blood Disorders Center (Boston, USA). Several interventions aimed at reducing toxic deaths and abandonment were implemented, including a reduced‐intensity treatment regimen and a psychosocial effort targeting abandonment. We performed a cohort study to assess impact.Results
The Study Population comprised 99 children with ALL diagnosed between 2007 and 2010, and the Historic Cohort comprised 181 children treated prior to the study interventions (1995–2004). Significant improvements were achieved in the rate of deaths in complete remission (13% to 3%; P = 0.005), abandonment (32% to 9%; P < 0.001), and event‐free survival with abandonment considered an event (47% to 65% at 2 years; P = 0.016). However, relapse rate did not improve. Medically unnecessary treatment delays were common, and landmark analysis revealed that initiating the PIII phase of therapy ≥4 weeks delayed predicted markedly inferior disease‐free survival (P = 0.016). Conversely, patients who received therapy without excessive delays had outcomes approaching those achieved in high‐income countries.Conclusions
Implementation of a twinning program was followed by reductions in abandonment and toxic deaths, but relapse rate did not improve. Inappropriate treatment delays were common and strongly predicted treatment failure. These findings highlight the importance of adherence to treatment schedule for effective therapy of ALL. Pediatr Blood Cancer 2015;62:1395–1402. © 2015 Wiley Periodicals, Inc. 相似文献22.
Alfonso Anselmi JoséAngel Suarez Guillermo Anselmi Frederico Moleiro Claudia de Suarez Victor Ruesta 《The American journal of cardiology》1975,35(1):97-102
Seventeen year old identical twin brothers with no family history of cardiopathy began experiencing palpitations almost simultaneously. In both, examination revealed marked cardiomegaly and hypokinesia of the ventricular walls, and clinical and radiologic signs of progressive cardiac failure developed a few days later. Both boys died suddenly, 49 days and 5 months, respectively, after the initial examination. Electrocardiographic and vectorcardiographic studies revealed a severe intraventricular conduction disturbance that coincided with histologic changes in the myocardial tissue, including profuse interstitial fibrosis, hypertrophy and degeneration of the myocardial fibers, aberrant arrangement of the muscular fibers and considerable alteration of the structure of cardiac tissue. In the absence of hereditary and chromosomal factors, and excluding possible viral intervention during fetal life, it is believed that a teratogenic factor can produce the structural alterations of the tissue and derangement of the fibers observed in these hearts.The irregular contractions of the heart at the level of the net-like meshwork, disarrangement of myocardial fibers, and adaptative mechanisms of the heart inherent in the destruction of the contractile tissue contributed to the functional cardiac disorders that resulted in congestive heart failure and sudden death in these twins. 相似文献
23.
BACKGROUND: Questions remain as to the existence of a class effect amongst angiotensin converting enzyme (ACE) inhibitors, and some literature suggests that pharmacological effects and outcomes may be determined by an ACE inhibitor's propensity to penetrate and inhibit the ACE enzyme at the vascular tissue level. Because vascular inflammation contributes to adverse outcomes following acute myocardial infarction (AMI), and angiotensin II influences inflammation at the vascular level, we hypothesized that high-tissue penetrating ACE inhibitors would provide more favorable effects on C-reactive protein (CRP) after AMI compared to low-tissue penetrating ACE inhibitors. METHODS AND RESULTS: In a randomized open-label trial, patients received the high-tissue penetrating quinapril (n = 15) or low-tissue penetrating enalapril (n = 15) following AMI. C-reactive protein was measured at baseline and periodically over 14 days following drug initiation. All baseline characteristics and blood pressure response to treatment between groups were equivalent. Prior to initiating study medication, CRP concentrations (mg/g) were similar between enalapril and quinapril (0.327 +/- 0.571 versus 0.273 +/- 0.380, respectively, p = 0.77). The percent magnitude of change in CRP concentrations favored quinapril at all time points, starting 12 h after treatment initiation. When characterizing CRP production during treatments, the time courses were significantly different and demonstrated lower CRP concentrations with quinapril (p = 0.0107). CONCLUSIONS: Overall, this investigation into the importance of ACE inhibitor tissue penetration on a common marker of vascular inflammation, suggests a potential vascular anti-inflammatory benefit with a more highly tissue penetrating ACE inhibitor following AMI. Further investigation into the true pharmacological similarities and differences amongst this class of drugs is warranted. 相似文献
24.
Harry Sokol Sophie Georgin-Lavialle Danielle Canioni Stéphane Barete Gandhi Damaj Erinn Soucie Julie Bruneau Marie-Olivia Chandesris Felipe Suarez Jean-Marie Launay Achille Aouba Catherine Grandpeix-Guyodo Fanny Lanternier Bernard Grosbois Christian de Gennes Pascal Cathébras Olivier Fain Nadia Hoyeau-Idrissi Patrice Dubreuil Olivier Lortholary Laurent Beaugerie Brigitte Ranque Olivier Hermine 《The Journal of allergy and clinical immunology》2013
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27.
RotaFlow and CentriMag Extracorporeal Membrane Oxygenation Support Systems as Treatment Strategies for Refractory Cardiogenic Shock 下载免费PDF全文
28.
29.
Mayra S. Coutinho Eloah Latocheski Jannyely M. Neri Ana C. O. Neves Josiel B. Domingos Lívia N. Cavalcanti Luiz H. S. Gasparotto Edgar P. Moraes Fabrício G. Menezes 《RSC advances》2019,9(51):30007
The development of nanoprobes for selective detection of metal ions in solution has attracted great attention due to their impact on living organisms. As a contribution to this field, this paper reports the synthesis of silver nanoparticles modified with rutin in the presence of ascorbic acid and their successful use as a chromogenic probe for the selective detection of Fe3+ in aqueous solution. Limits of detection and quantification were found to be 17 nmol L−1 and 56 nmol L−1, respectively. The sensing ability is proposed to proceed via an iron-induced nanoparticle growth/aggregation mechanism. A practical approach using image analysis for quantification of Fe3+ is also described.The use of rutin-modified silver nanoparticles for selective detection and sensitive quantification of Fe3+ in aqueous solution is described. Metal ions are key species in nature due to their essential functions in living organisms.1,2 On the other hand, heavy metals as well as essential metals at abnormally high levels are toxic.2 Iron, for instance, in addition to its popular use in industry and construction, is essential to the human body and active in biological processes. Although the trivalent form of iron is particularly important for oxygen transport in blood and the mitochondrial respiratory chain, high levels of this cation are associated with important pathologies.3,4 The detection of metal ions in aqueous solution is traditionally performed by methods including atomic absorption spectrometry,5 electrochemical measurements,6,7 and inductively coupled plasma techniques,8 among others. However, these techniques have important drawbacks, notably the need for sophisticated instrumentation, in addition to being time-consuming and requiring laborious procedures. To overcome these issues, the development of chromogenic and fluorogenic chemosensors for the selective detection of metal-targets has attracted great attention, especially due to the possibility of fast, sensitive and non-expensive analysis.9,10 In the last decade, nanoscaled materials have been reported as selective probes for metal ions, including Fe3+.11–24Silver nanoparticles (AgNPs) are of particular interest because of the affordable price of starting materials, ease of controlling size and morphology, possibility to functionalize their surface with organic molecules, and optical properties that enable detection of a variety of analytes via simple UV-vis spectroscopy and digital image analysis. Furthermore, applications of AgNPs are also biotechnologically relevant due to the possibility of green synthetic protocols, including the use of plant extracts,25 natural sources,26 glycerol,27 among others.Flavonoids are secondary metabolites naturally found in fruits and other vegetables with relevant roles due to their nutritional, pharmaceutical and medicinal properties.28 Because of their adequate structural features, flavonoids are candidates to be employed in the synthesis of AgNPs.26 Rutin (RU), a sugar-based flavonoid, may be employed as reducing agent in the synthesis of AgNPs along with a stabilizer such as polyvinylpyrrolidone (PVP)26 or used as crude plant extract component.29,30This paper reports the use of RU-modified AgNPs (RU-AgNPs) as a chromogenic probe for Fe3+ in aqueous medium in the presence of ascorbic acid (AA). Sensing ability of RU-AgNPs for the selective detection of Fe3+ toward other metal cations was investigated with UV-vis spectroscopy analysis. These data and transmission electronic microscopy (TEM) results allowed a mechanistic proposal involved in the selective detection of Fe3+ by RU-AgNPs. Furthermore, a practical approach based on correlation of images of solutions obtained with a conventional smartphone and chemometrics was employed for a simpler quantification of Fe3+ in aqueous medium.Initially, the order of reagent combination was investigated in the synthesis of RU-AgNPs. Concentration of RU ranged from 0.10 to 0.50 mmol L−1, while concentrations of other components were fixed at 0.20 mmol L−1 AgNO3, 0.10 mmol L−1 AA and 0.10 M NaOH. Water was used as solvent in all cases. Narrower surface plasmon resonance (SPR) bands were obtained from adding a solution of AA and NaOH to a solution containing RU and AgNO3 (Fig. 1a) against the addition of RU, AA, and NaOH to AgNO3 solution (Fig. S1a – ESI†), or the addition of RU and NaOH to a solution of AA and AgNO3 (Fig. S1b†). RU-AgNPs obtained from the condition presented in Fig. 1a are small (4.1 nm average diameter) and considerably polydisperse (standard deviation of 4.7 nm), however, presenting only one population (Fig. 1b and S2†). A study of the influence of RU concentration (0.10 to 0.50 mmol L−1) on the stability of RU-AgNPs over time indicated that 0.10 mmol L−1 RU generates more stable RU-AgNPs (Fig. S3†). Next, a study on the influence of pH indicated that RU-AgNPs are only stable under strong alkaline conditions (pH 12.5 or higher) (Fig. S4†).Open in a separate windowFig. 1(a) UV-vis analysis of RU-AgNPs under strong alkaline condition (pH > 12.5) based on the order of adding reagents (RU, 0.10 to 0.50 mmol L−1; AgNO3, 0.20 mmol L−1; AA, 0.10 mmol L−1; NaOH, 0.10 mmol L−1); (b) TEM image of RU-AgNPs under the selected condition.The ability of RU-AgNPs to sense metal cations was investigated by both naked-eye and UV-vis spectroscopy analysis (Fig. 2). The separate addition of 10 μmol L−1 of several metal cations (Fe3+, Co2+, Zn2+, Sr2+, Cu2+. Al3+, Ba2+, Cd2+, Pb2+, Ni2+, Mg2+, Hg2+, Cu+ and Cr3+) to solutions of RU-AgNPs (prepared according to Fig. 1a) indicated that only Fe3+ induces a significant colorimetric change in the final aspect of solution after 50 minutes (Fig. 2a).Open in a separate windowFig. 2Naked-eye (a) and UV-vis (b) analysis of RU-AgNPs in absence (control, C) and presence of 10 μmol L−1 of selected metal cations (Fe3+, Co2+, Zn2+, Sr2+, Cu2+. Al3+, Ba2+, Cd2+, Pb2+, Ni2+, Mg2+, Hg2+, Cu+ and Cr3+) after 50 min; (c) calibration curve obtained by the addition of different amounts (0 to 10 μmol L−1) of Fe3+ to solutions of RU-AgNPs; (d) TEM image of RU-AgNPs after addition of Fe3+ (10 μmol L−1). In all experiments, RU-AgNPs were prepared in the presence of ascorbic acid.The results presented in Fig. 2a are consistent with the UV-vis spectroscopy analysis (Fig. 2b). Co2+ ions also induce some change in the system, however at a considerably smaller extension than Fe3+. In this study, AA played a crucial role in the selective detection of Fe3+ by the referred nanoprobe. In the absence of AA, Co2+ (mainly) as well as other cations induce stronger colorimetric and spectral changes (Fig. S5a and b,† respectively) in the analysis of solutions of RU-AgNPs when compared to the system containing AA. This selectivity may arise from two possible reasons: (i) preservation of RU by avoiding its oxidation in the reduction of Ag+ ions; (ii) coordination of ascorbate anion to cations other than Fe3+.Interaction of RU-AgNPs and Fe3+ (10 μmol L−1) stabilizes after approximately 40 minutes (Fig. S6†). Next, a calibration curve was built from the direct relationship between the absorbance at 396 nm and the concentration of Fe3+ (Fig. 2c), presenting a good correlation (R2 = 0.9929). The limits of detection and quantification were found to be 17 nmol L−1 and 56 nmol L−1, respectively, which is very satisfactory.13,14 The influence of other cations in the detection of Fe3+ was investigated by UV-vis spectroscopy. Fig. S7† clearly demonstrates that there are only small changes when a second cation (30 μmol L−1) is added together with Fe3+ to the RU-AgNPs solution.Mechanistically, the detection of Fe3+ by RU-AgNPs in aqueous medium proceeds via a growth/aggregation-combined process. This proposal is first evidenced by UV-vis analysis due the suppression of SPR band (Fig. 2b), a behavior consistent with the literature.31,32 Interestingly, TEM analysis clearly shows a growth in AgNPs size after addition of Fe3+ to the solution (Fig. 2d), resulting in a final single AgNPs population with average diameter of 14.7 nm ± 8.9 nm. Due to the strong alkaline medium, the main specie responsible for the behavior of NPs is likely to be Fe(OH)3. A schematic illustration of the mechanism involving aggregation of RU-AgNPs induced by the addition of Fe3+ is presented in Fig. 3. AgNPs are initially formed by adsorption of anionic RU to the silver surface via deprotonated 5-hydroxychromen-4-one moiety. This is supported by the literature33 and confirmed by alteration in the 1800–1500 cm−1 region of the RU infrared spectra before and after coordination with silver (Fig. S9†). Afterwards, the addition of Fe3+ induces the formation of a coordination complex through an anionic catechol group, in which at least 2 : 1 ligand–Fe3+ stoichiometry is required for an aggregated effect.Open in a separate windowFig. 3Mechanistic proposal for growth/aggregation of RU-AgNPs in the presence of Fe3+. Insert: binding model for RU-AgNPs.Due to increasing interest in image processing as an analytical tool for many purposes,34,35 Multiple Linear Regression was employed to verify the capacity of the RU-AgNPs to probe Fe3+ standards at distinct concentrations, as presented in Fig. 4. The curve was obtained by plotting the color absorbances RGB-based values versus the concentrations of Fe3+ standards after RU-AgNPs interaction. Predicted iron is a vector based on RGB values that were then extracted from the filtered images and inserted in the equation described by Beer–Lambert law in order to generate the absorbances for the construction of the analytical curve. A linear behavior between the predicted response and the measured concentrations was observed (R2 = 0.9806).Open in a separate windowFig. 4Calibration curve for Fe3+ analysis showing the predicted iron (RGB) vs. iron(iii) concentration (1 to 8 μmol L−1). Adjusted R2 = 0.9806.Regression coefficients of the calibration model (using the R, G and B channels simultaneously) obtained by MLR method are shown in eqn (1):[Fe3+] = 44.5R − 4.9G − 16.4B + 5.11where Fe3+ concentration is the dependent variable (Predicted Iron), 5.1 is the intercept (β0), 44.5, −4.9 and −16.4 are the regression coefficients of the independent variables (R, G and B channels, respectively).It is possible to observe an interesting performance of the method using the three RGB color channels allied with MLR to quantify the Fe3+ content, which presented reasonable deviations in its responses considering that it is simple and low-cost. The good linearity is similar to other colorimetric methods such as sodium determination in seawater and coconut water (R2 > 0.91) by Moraes and coauthors,36 or iron(ii) in simulated seawater (R2 = 0.9993) by Gasparotto et al.37Second order regression was applied to the dataset to obtain a better adjustment, resulting in an adjusted R-squared of 0.9955. RGB values were then inserted in eqn (2) in order to generate the construction of the correlation:[Fe3+] = 14.4R + 30.7G − 23.4B − 398RG − 348RB − 0.8BG − 978R2 + 695G2 + 26.9B2 + 4.52This paper reports the use of AgNPs functionalized with RU as nanoprobes for selective detection and sensitive quantification of Fe3+ in aqueous solution. The synthesis of RU-AgNPs is reproducible, easily performed and requires no stabilizer agent other than RU. AA has a crucial role in the selectivity by either the avoidance of oxidation of RU by silver and/or coordination of ascorbate with other cations. The literature brings relevant examples of chromogenic and fluorogenic chemosensors for selective detection of Fe3+ in solution. Many of these artificial organic receptors present high selectivity and relevant limits of detection, requiring, however, very specific reagents and laborious synthetic procedures.38–41 Metal-based nanoparticles have emerged as potential probes for detection of Fe3+.11–16 Although effective in Fe3+ sensing, the synthesis of these nanoprobes require some toxic reagents, such as NaBH4 or PVP, use plant extracts, which may lead to some drawbacks, such as the understanding of the sensing mechanism. In contrast, our method is based on commercially available, nontoxic, low-cost reagents. Fe3+ sensing performed satisfactorily in the 1–10 μmol L−1 range, and the limit of detection obtained with this method (17 nmol L−1) is comparable to the most sensitive methods reported in literature. A mechanism for the detection of Fe3+ by RU-AgNPs involves a combined growth/aggregation of the NPs. There is a still limited number of nanoscaled systems reported as being selective and sensitive in the detection of Fe3+, which reinforces the relevance of the method reported herein. The linearity range obtained by both UV-vis spectroscopy and image analysis comprises the maximum of residual Fe3+ in drinking water according to the European and US legislations.15,42 相似文献
30.
da Silva LC de Almeida Freitas R de Andrade MP Piva MR Martins-Filho PR de Santana Santos T 《The Journal of craniofacial surgery》2012,23(3):e214-e218
To prevent rejection of kidney transplants, patients must be kept in immunosuppressive therapy for a long time, which includes the use of drugs such as cyclosporine, azathioprine, cyclophosphamide, and prednisone. The action of these drugs reduces the general immune response of transplant patients and thus increases their susceptibility to infections. Moreover, these drugs increase the potential of developing lesions. Therefore, oral hygiene in kidney transplant recipients contributes to maintenance of the transplanted organ and its function. Thus, an investigation of oral lesions could be counted as a notable work. The aim of this study was to investigate oral lesions in a group of 21 kidney transplant patients under immunosuppressive therapy attended during a 1-year period in the Nephrology Department of the Federal University of Sergipe, Brazil. Data related to sex, age, etiology of renal disease, types of renal transplant, time elapsed after transplantation, immunosuppressive treatment, use of concomitant agents, and presence of oral lesions were obtained. All patients received a kidney transplant from a living donor, and the mean posttransplantation follow-up time was 31.6 months; 71.5% used triple immunosuppressive therapy with cyclosporine A, azathioprine, and prednisone. Ten patients were also treated with calcium-channel blockers. Of the 21 transplant patients, 17 (81%) presented oral lesions. Gingival overgrowth was the most common alteration, followed by candidiasis and superficial ulcers. One case of spindle cell carcinoma of the lower lip was observed. Oral cavity can harbor a variety of manifestations related to renal transplantation under immunosuppressive therapy. 相似文献