Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 329
Filtrar
1.
Acta Biomater ; 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31634626

RESUMO

Single ventricle heart defects (SVDs) are congenital disorders that result in a variety of complications, including increased ventricular mechanical strain and mixing of oxygenated and deoxygenated blood, leading to heart failure without surgical intervention. Corrective surgery for SVDs are traditionally handled by the Fontan procedure, requiring a vascular conduit for completion. Although effective, current conduits are limited by their inability to aid in pumping blood into the pulmonary circulation. In this report, we propose an innovative and versatile design strategy for a tissue engineered pulsatile conduit (TEPC) to aid circulation through the pulmonary system by producing contractile force. Several design strategies were tested for production of a functional TEPC. Ultimately, we found that porcine extracellular matrix (ECM)-based engineered heart tissue (EHT) composed of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and primary cardiac fibroblasts (HCF) wrapped around decellularized human umbilical artery (HUA) made an efficacious basal TEPC. Importantly, the TEPCs showed effective electrical and mechanical function. Initial pressure readings from our TEPC in vitro (0.68 mmHg) displayed efficient electrical conductivity enabling them to follow electrical pacing up to a 2 Hz frequency. This work represents a proof of principle study for our current TEPC design strategy. Refinement and optimization of this promising TEPC design will lay the groundwork for testing the construct's therapeutic potential in the future. Together this work represents a progressive step toward developing an improved treatment for SVD patients. Statement of Significance: Single Ventricle Cardiac defects (SVD) are a form of congenital disorder with a morbid prognosis without surgical intervention. These patients are treated through the Fontan procedure which requires vascular conduits to complete. Fontan conduits have been traditionally made from stable or biodegradable materials with no pumping activity. Here, we propose a tissue engineered pulsatile conduit (TEPC) for use in Fontan circulation to alleviate excess strain in SVD patients. In contrast to previous strategies for making a pulsatile Fontan conduit, we employ a modular design strategy that allows for the optimization of each component individually to make a standalone tissue. This work sets the foundation for an in vitro, trainable human induced pluripotent stem cell based TEPC.

3.
Clin Teach ; 16(4): 339-344, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31397104

RESUMO

BACKGROUND: Training in clinical medicine involves exposure to complex ethical and emotional situations. Reflection aids in the development of personal belief systems and improves self-awareness. Students may be reluctant to participate when reflection is mandatory and may be concerned about retaliation when the facilitator has a role in evaluations. Near-peers are institutional equals with more experience than the participants and may be well suited to facilitate reflection. METHODS: A quarterly near-peer-facilitated reflective writing workshop (RWW) was implemented in the mandatory clinical curriculum at a single institution. Qualitative feedback forms were solicited and were analysed through an iterative and inductive consensus process. An end-of-year web-based survey was distributed to test the hypotheses generated from our analysis of the feedback forms. RESULTS: There were 82 responses (80%) to the web-based survey and 266 (65%) feedback forms were collected. Although few students reported using writing as a coping mechanism, the RWW was viewed favourably, with 62% indicating that they would attend if optional. The structured prompts aided reflection. Students reported a higher likelihood of discussing difficult topics (doubts about medicine as a career, personal shortcomings, harassment and burnout) in sessions led by a near-peer than by a faculty member. The workshop created a safe space to reflect, increased a sense of camaraderie and helped normalise experiences. [The workshop] humanised the clinical experience, gave new perspective and reminded students of their positive personal accomplishments DISCUSSION: The near-peer-facilitated RWW is a novel intervention aimed at developing reflective practice and coping with the challenges of entering clinical medicine. It is highly structured and has been incorporated into the mandatory curriculum. It was well received by students, is generalisable and is easily implementable.

4.
Expert Opin Drug Saf ; 18(9): 841-852, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31238745

RESUMO

Introduction: Systemic Autoimmune Diseases (SADs) include systemic lupus erythematosus, antiphospholipid antibody syndrome, rheumatoid arthritis, systemic sclerosis, Sjogren's syndrome, mixed connective tissue disease, idiopathic inflammatory myopathies and vasculitis. SADs often occur in women of childbearing age and can affect fertility. Both infertility treatments and fertility preservation techniques are thus often indicated. Areas covered: The literature regarding the safety of fertility-related drugs for both fertility preservation and infertility treatment in patients affected by SADs was reviewed. Based on current knowledge, all the options for fertility preservation should be contemplated in patients with SADs who are at risk for fertility loss, including GnRH analogue administration, oocyte/embryo vitrification and ovarian tissue cryopreservation. Similarly, if pregnancy is not contraindicated in a patient with a SAD, neither should be any fertility treatment. Expert opinion: Women with SADs should postpone conception until a stable disease has been achieved for at least 6 months. When infertility treatments are needed, women with antiphospholipid antibodies should receive concomitant anticoagulation. If in vitro fertilization/intra-cytoplasmic sperm injection and embryo transfer is required, ovarian hyperstimulation and the inherent risk of thrombosis should be eliminated by GnRH-agonist trigger and cycle segmentation. Counselling about adherence to anti-rheumatic therapy to prevent disease exacerbations is also critical.


Assuntos
Doenças Autoimunes/complicações , Preservação da Fertilidade/métodos , Infertilidade Feminina/terapia , Anticorpos Antifosfolipídeos/imunologia , Doenças Autoimunes/fisiopatologia , Criopreservação/métodos , Feminino , Fertilização In Vitro/métodos , Humanos , Infertilidade Feminina/etiologia , Gravidez , Técnicas de Reprodução Assistida
5.
J Physiol ; 2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30624779

RESUMO

Cardiomyocytes derived from human induced pluripotent stem cells (iPSCs) provide a unique opportunity to understand the pathophysiological effects of genetic cardiomyopathy mutations. In particular, these cells hold the potential to unmask the effects of mutations on contractile behaviour in vitro, providing new insights into genotype-phenotype relationships. With this goal in mind, several groups have established iPSC lines that contain sarcomeric gene mutations linked to cardiomyopathy in patient populations. Their studies have employed diverse systems and methods for performing mechanical measurements of contractility, ranging from single cell techniques to multicellular tissue-like constructs. Here, we review published results to date within the growing field of iPSC-based sarcomeric cardiomyopathy disease models. We devote special attention to the methods of mechanical characterization selected in each case, and how these relate to the paradigms of classical muscle mechanics. An appreciation of these somewhat subtle paradigms can inform efforts to compare the results of different studies and possibly reconcile discrepancies. Although more work remains to be done to improve and possibly standardize methods for producing, maturing, and mechanically interrogating iPSC-derived cardiomyocytes, the initial results indicate that this approach to modelling cardiomyopathies will continue to provide critical insights into these devastating diseases.

6.
Anaesthesia ; 74(3): 340-347, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30666622

RESUMO

Proper placement of the tracheal tube requires confirmation, and the predominant method in addition to clinical signs is the presence of end-tidal carbon dioxide. Such is the importance of confirmation that novel methods may also have a place. We previously demonstrated using ex-vivo swine tissue a unique spectral reflectance characteristic of tracheal tissue that differs from oesophageal tissue. We hypothesised that this characteristic would be present in living swine tissue and human cadavers. Reflectance spectra in the range 500-650 nm were captured using a customised fibreoptic probe, compact spectrometer and white light source from both the trachea and the oesophagus in anesthetised living swine and in human cadavers. A tracheal detection algorithm using ratio comparisons of reflectance was developed. The existence of the unique tracheal characteristic in both in-vivo swine and cadaver models was confirmed (p < 0.0001 for all comparisons between tracheal and oesophageal tissue at all target wavelengths in both species). Furthermore, our proposed tracheal detection algorithm exhibited a 100% positive predictive value in both models. This has potential utility for incorporation into airway management devices.


Assuntos
Esôfago/diagnóstico por imagem , Intubação Intratraqueal/métodos , Traqueia/diagnóstico por imagem , Animais , Cadáver , Feminino , Tecnologia de Fibra Óptica , Humanos , Suínos
7.
Food Chem ; 270: 214-222, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30174037

RESUMO

During the industrial refining process of edible oils and the manufacture of oil-based foodstuff, contaminants such as 3-monochloropropanediol (3-MCPD) fatty acid diesters can be produced. One hundred samples of different edible oils and related fatty food purchased from local Spanish markets were analyzed to evaluate the occurrence of these contaminants. Data of seven 3-MCPD diesters together with corresponding total 3-MCPD equivalents are presented. The procedure is based on a modified QuEChERS protocol followed by LC-MS/MS analysis. Extra virgin olive oil (EVOO) and unrefined oils did not contain detectable levels of the target analytes. The highest levels of 3-MCPD diesters were found in palm oils, for 1,2-Dilinoleoyl-3-chloropropanediol (LILI) and 1-2-Bispalmitoyl-3-chloropropanediol (PAPA) with concentrations close to 10 mg kg-1 and in the lipid fraction of margarines (8.09, 3.77 and 3.72 mg kg-1 for LILI, PAPA and 1-Oleoyl-2-linoleoyl-3-chloropropanediol (OLLI), respectively).


Assuntos
Ésteres/química , Contaminação de Alimentos/análise , Óleos Vegetais/análise , Óleos Vegetais/química , Espectrometria de Massas em Tandem , alfa-Cloridrina
8.
Rev. argent. dermatol ; 99(4): 43-50, dic. 2018.
Artigo em Espanhol | LILACS-Express | ID: biblio-985202

RESUMO

RESUMEN: La enfermedad de Pagetextramamaria es un adenocarcinoma intraepitelial,extremadamente raro. Su diagnóstico suele ser tardío pudiendo demorarse hasta tres años. Debemos hacer un diagnóstico diferencial con otras enfermedades dermatológicas, que pueden cursar igual. El diagnóstico definitivo es histopatológico. La cirugía es el tratamiento de elección, siendo la cirugía micrográfica de Mohs la más empleada. Existen tratamientos tópicos tales como el imiquimod, que pueden ser útiles. En general el pronóstico suele ser favorable.


SUMMARY: Extramammary Paget disease is an intraephithelial adenocarcinoma very rare. Its diagnosis is usually late and may take up to 3 years. We must make a differential diagnosis with other dermatological diseases that can occur equally. The definitive diagnosis is histopatological. Surgery is the gold standard treatment, Mohs micrographic surgery being the most used. There are topical treatments such as imiquimod that may be useful. In general, the prognosis is usually favorable.

9.
Anal Bioanal Chem ; 2018 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-30357441

RESUMO

Drugs of abuse and new psychoactive substances (NPS) for recreational purposes are in constant evolution, and their consumption constitutes a significant risk to public health and road safety. The development of an analytical methodology to confirm the intake of illicit drugs in biological fluids is required for an effective control of these substances. An ultra-performance liquid chromatography-tandem mass spectrometry method (UPLC-MS/MS) was developed for simultaneous determination of 10 synthetic cathinones and 10 illicit drugs in oral fluid easily sampled through non-invasive maneuvers. The UPLC-MS/MS method was coupled to an ultrasound-assisted dispersive liquid-liquid microextraction (US-DLLME), which is a miniaturized and inexpensive technique that uses reduced volumes of solvents and samples. The US-DLLME was optimized by using a 213441//18 asymmetric screening design and a Doehlert design. Sample volume, dispersion and extraction solvent volumes, pH, US time, and amount of sodium chloride were evaluated. The US-DLLME-UPLC-MS/MS method was validated according to international guidelines. Limits of quantitation (LOQs) ranged from 0.25 to 5 ng mL-1, and the linear range spanned from LOQ to 500 ng mL-1 with R2 higher than 0.9907, for most of the target drugs. Precision ranged from 1.7 to 14.8 %RSD. Accuracy, i.e., extraction recovery, ranged from 74 to 129%. The proposed method was successfully applied to the analysis of 15 samples from patients on a drug detoxification program.

10.
Pulmonology ; 2018 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-29739657

RESUMO

INTRODUCTION AND OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a major public health problem. The aim of this study was to ascertain the prevalence of COPD and whether such prevalence was positively or negatively associated with COPD admissions, using all the data of a regional health care system. MATERIALS AND METHODS: We designed a descriptive cross-sectional study which included all subjects aged over 45 years, diagnosed with COPD in primary care in 2013. We also calculated the number of such patients who had a record of hospital admissions due to this disease. COPD prevalence and incidence of admissions were calculated. Poisson regression models were then used to analyse the association between cases with diagnosis of COPD and admissions due to COPD, by sex, adjusting for socio-demographic variables and distance to hospital. Sensitivity subanalyses were performed by reference to the respective municipal rurality indices. RESULTS: Median municipal prevalence of COPD was 5.29% in men and 2.19% in women. Among patients with COPD, 28.22% of men and 16.00% of women had at least one hospital admission. The relative risk of admission per unit of the standardised prevalence ratio was 0.37 (95% CI 0.34-0.41) for men and 0.39 (95% CI 0.34-0.45) for women. CONCLUSIONS: There is a significant negative association between COPD prevalence and hospital admissions due to this disease. The proportion of admissions is lower in municipalities lying furthest from hospitals. There is considerable municipal variability in terms of COPD prevalence and proportion of admissions. In-depth attention should be given to disease-management training programmes.

11.
J Chromatogr A ; 1548: 19-26, 2018 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-29555360

RESUMO

A fast and effective method using a modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) approach which includes partitioned liquid-liquid extraction (PLLE) and dispersive solid phase extraction (dSPE) clean-up step for the determination of seven 3-monochloropropane-1,2-diol (3-MCPD) fatty acid diesters in vegetable oils is developed and validated according to the Food and Drug Administration (FDA) guidelines. Due to the complexity of the matrices, combination of silica based sorbents (Silica Strong Anion Exchange (Si-SAX), Supel™ QuE Z-Sep+ (Z-Sep+) and Primary Secondary Amine (PSA) were tested for lipid removal. The effect of several experimental factors on the efficiency of the extraction procedure was studied by a screening design 3422//16 and a response surface Doehlert design. The separation and determination was carried out by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The method provided suitable linearity (r2 > 0.9960), precision (relative standard deviation (RSD) lower than 10%) and accuracy, in terms of recovery. The limits of detection (LOD) and limits of quantification (LOQ) ranged from 10 to 20 µg kg -1 and from 25 to 50 µg kg-1, respectively. The recoveries at three spiking levels of 100, 250, and 500 µg kg-1 were over the range of 71.4-122.9% with RSD lower than 13%. The method was successfully applied in edible oils and fatty food samples. The results provide valuable information to assess the risk of exposure to these foodborne contaminants.


Assuntos
Cromatografia Líquida/métodos , Ésteres/análise , Extração Líquido-Líquido/métodos , Óleos Vegetais/química , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , alfa-Cloridrina/análise , Limite de Detecção , Margarina/análise , Reprodutibilidade dos Testes
12.
Enferm. intensiva (Ed. impr.) ; 29(1): 21-31, ene.-mar. 2018. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-171037

RESUMO

Introducción: La enfermedad crítica en el paciente pediátrico incluye desde una patología aguda en un niño sano a una agudización de una enfermedad crónica, hecho que ha conllevado centrar su atención clínica en las Unidades de Cuidados Intensivos Pediátricos. El rol del/la enfermero/a pediátrico/a se centra también en promover el confort en estos pacientes críticos. Por este motivo, es necesario disponer de instrumentos de medida que permitan un correcto sensado del grado de confort. Objetivo: Describir el proceso de validación de contenido de una escala de confort crítico pediátrico mediante el empleo de una metodología mixta. Material y métodos: Se realizó una adaptación transcultural del inglés al español mediante el método de traducción-retraducción de la Comfort Behavior Scale. Posteriormente, se validó el contenido de la misma mediante una metodología mixta. Esta segunda etapa se dividió en una fase cuantitativa empleando un cuestionario ad hoc donde se valoró la relevancia/pertinencia y el redactado de cada dominio/ítem de la escala y en una cualitativa donde se realizaron dos reuniones con profesionales sanitarios, pacientes y un familiar siguiendo las recomendaciones de la metodología Delphi. Resultados: Todos los ítems y dominios obtuvieron un índice de validez de contenido >0,80, exceptuando el movimiento físico, en su relevancia, que obtuvo un 0,76. El índice global de validez de contenido de la escala fue de 0,87 (elevado). Durante la fase cualitativa se reformularon y/o eliminaron ítems de cada uno de los dominios de la escala para hacerla más comprensible y aplicable. Conclusiones: El empleo de una metodología mixta de validación de contenido otorga riqueza y sensibilidad evaluatoria al instrumento a diseñar (AU)


Introduction: Critical illness in paediatric patients includes acute conditions in a healthy child as well as exacerbations of chronic disease, and therefore these situations must be clinically managed in Critical Care Units. The role of the paediatric nurse is to ensure the comfort of these critically ill patients. To that end, instruments are required that correctly assess critical comfort. Objective: To describe the process for validating the content of a paediatric critical comfort scale using mixed-method research. Material and Methods: Initially, a cross-cultural adaptation of the Comfort Behavior Scale from English to Spanish using the translation and back-translation method was made. After that, its content was evaluated using mixed method research. This second step was divided into a quantitative stage in which an ad hoc questionnaire was used in order to assess each scale's item relevance and wording and a qualitative stage with two meetings with health professionals, patients and a family member following the Delphi Method recommendations. Results: All scale items obtained a content validity index >0.80, except physical movement in its relevance, which obtained 0.76. Global content scale validity was 0.87 (high). During the qualitative stage, items from each of the scale domains were reformulated or eliminated in order to make the scale more comprehensible and applicable. Conclusions: The use of a mixed-method research methodology during the scale content validity phase allows the design of a richer and more assessment-sensitive instrument (AU)


Assuntos
Humanos , Masculino , Feminino , Criança , Enfermagem de Cuidados Críticos/métodos , Enfermeiras Pediátricas/organização & administração , Papel do Doente , Psicometria/métodos , Inquéritos e Questionários , Técnica Delfos , Comportamento Infantil/psicologia , Análise de Dados/métodos
13.
Clin Rheumatol ; 37(4): 999-1009, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29214548

RESUMO

The objective of the study is to determine the importance of the mode of onset as prognostic factor in systemic sclerosis (SSc). Data were collected from the Spanish Scleroderma Registry (RESCLE), a nationwide retrospective multicenter database created in 2006. As first symptom, we included Raynaud's phenomenon (RP), cutaneous sclerosis, arthralgia/arthritis, puffy hands, interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), and digestive hypomotility. A total of 1625 patients were recruited. One thousand three hundred forty-two patients (83%) presented with RP as first symptom and 283 patients (17%) did not. Survival from first symptom in those patients with RP mode of onset was higher at any time than those with onset as non-Raynaud's phenomenon: 97 vs. 90% at 5 years, 93 vs. 82% at 10 years, 83 vs. 62% at 20 years, and 71 vs. 50% at 30 years (p < 0.001). In multivariate analysis, factors related to mortality were older age at onset, male gender, dcSSc subset, ILD, PAH, scleroderma renal crisis (SRC), heart involvement, and the mode of onset with non-Raynaud's phenomenon, especially in the form of puffy hands or pulmonary involvement. The mode of onset should be considered an independent prognostic factor in systemic sclerosis and, in particular, patients who initially present with non-Raynaud's phenomenon may be considered of poor prognosis.


Assuntos
Artralgia/etiologia , Hipertensão Pulmonar/etiologia , Doenças Pulmonares Intersticiais/etiologia , Doença de Raynaud/etiologia , Escleroderma Sistêmico/diagnóstico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/fisiopatologia , Índice de Gravidade de Doença , Avaliação de Sintomas
14.
Enferm Intensiva ; 29(1): 21-31, 2018 Jan - Mar.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28760690

RESUMO

INTRODUCTION: Critical illness in paediatric patients includes acute conditions in a healthy child as well as exacerbations of chronic disease, and therefore these situations must be clinically managed in Critical Care Units. The role of the paediatric nurse is to ensure the comfort of these critically ill patients. To that end, instruments are required that correctly assess critical comfort. OBJECTIVE: To describe the process for validating the content of a paediatric critical comfort scale using mixed-method research. MATERIAL AND METHODS: Initially, a cross-cultural adaptation of the Comfort Behavior Scale from English to Spanish using the translation and back-translation method was made. After that, its content was evaluated using mixed method research. This second step was divided into a quantitative stage in which an ad hoc questionnaire was used in order to assess each scale's item relevance and wording and a qualitative stage with two meetings with health professionals, patients and a family member following the Delphi Method recommendations. RESULTS: All scale items obtained a content validity index >0.80, except physical movement in its relevance, which obtained 0.76. Global content scale validity was 0.87 (high). During the qualitative stage, items from each of the scale domains were reformulated or eliminated in order to make the scale more comprehensible and applicable. CONCLUSIONS: The use of a mixed-method research methodology during the scale content validity phase allows the design of a richer and more assessment-sensitive instrument.

15.
Talanta ; 174: 454-461, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28738608

RESUMO

The emergence in recent years of potentially dangerous new psychoactive substances (NPS) that are not under international control has led to the development of multi-analyte procedures for their unequivocal quantification. A fast ultra-performance liquid chromatography-tandem mass spectrometry method (UPLC-MS/MS), in combination with a sample pretreatment based on microextraction by packed sorbent (MEPS), was for the first time used in this work for the simultaneous determination of NPS in oral fluid. This matrix is an effective alternative to typical biological samples for drug control in substitution therapy programs, and also for the prevention and reduction of traffic accidents. The proposed method allowed the separation and quantification of eleven synthetic cathinones, six opiates, scopolamine, cocaine and two metabolites in less than 3.0min by using appropriate isotope-labelled internal standards. The MEPS procedure, which is a miniaturized version of the SPE technique, is completed within 15min. The influence of variables such as the washing solution and eluent volumes, phase type, number of aspirate-dispense cycles and pH was investigated by using a 3441//16 asymmetric screening design and a response surface methodology based on a Doehlert design. The MEPS process performed optimally with a mixed-mode C8/SCX sorbent and a sample pH of 9. The proposed method was validated according to major guidelines and found to span the linear concentration range 0.5-500ngmL-1 (R2 ≥ 0.9903), and to be selective and precise (within- and between-day precision as %RSD were both lower than 13.7%). The accuracy, in terms of analyte extraction recovery, ranged from 75% to 125% for most of the analytes. The MEPS-UPLC-MS/MS method was successfully used to analyse twelve real samples from patients on a drug detoxification programme and proved an effective tool for drug monitoring.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Psicotrópicos/análise , Psicotrópicos/isolamento & purificação , Saliva/química , Microextração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Humanos , Limite de Detecção , Reprodutibilidade dos Testes , Solventes/química
16.
Eur J Clin Microbiol Infect Dis ; 36(8): 1511-1517, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28343274

RESUMO

OBJECTIVE: The aims of our study were to determine the factors associated with developing haematological toxicity (HT) in patients taking linezolid (LZD), to develop a predictive model of HT in these patients, and to evaluate factors associated with 30-day mortality. METHODS: This was an observational retrospective cohort study of patients treated for at least 5 days with LDZ in 2015. Demographic, clinical and analytical data were collected. Development of HT was defined as a 25% platelet count decrease between the basal count and the 1-week lab test. RESULTS: Five hundred forty-nine patients were finally included, mean age was 73.3 (SD 15.4) years, and 303 (55.2%) were men. One hundred seventy-five (30.1%) patients achieved HT criteria during treatment with LZD and 41 (7.5%) died. The final model included the presence of cerebrovascular disease (2 points), moderate or severe liver disease (2 points), renal failure (2 points) and basal platelet count less than 90,000/mm3 (8 points). This new model showed an AUC of 0.711 (IC 95% 0.664-0.757; p < 0.001) to predict the development of HT. The probability of HT based on this classification was 6.2, 29.9 and 76.5% for low (0-4 points), intermediate (5-10 points) and high risk (>10 points), respectively. The independent variables associated with 30-day mortality were metastatic solid tumor, lymphoma, age >75 years and HT. CONCLUSION: This score could help in the identification of patients with high risk for HT and assess the use of an antibiotic other than LZD, an important issue considering its relation with 30-day mortality observed in our study.


Assuntos
Antibacterianos/efeitos adversos , Técnicas de Apoio para a Decisão , Linezolida/efeitos adversos , Trombocitopenia/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Feminino , Humanos , Linezolida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Retrospectivos , Medição de Risco
17.
J Chromatogr A ; 1485: 8-19, 2017 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-28108082

RESUMO

A miniaturized and simple method based on digitally programmed microextraction by packed sorbent (eVol®-MEPS) coupled to ultra-performance liquid chromatography (UPLC) has been developed for quantitative determination of three synthetic cathinones and seven conventional drugs of abuse and metabolites. The influence of several extraction parameters, such as washing and elution solvents were tested. In addition important variables affecting MEPS performance, namely sample volume, sorbent drying time, washing solvent volume, elution volume, number of extraction cycles, sorbent phase and pH, were evaluated using an asymmetrical screening design. The optimal experimental conditions involved 300µL of plasma, loading 10×100µL of sample through a C8/SCX sorbent in a MEPS syringe placed in the semi-automatic eVol® system, washing using 150µL H2O:MeOH (90:10, v/v), drying for 0.5min and elution using 200µL dichloromethane:2-propanol:ammonium hydroxide (78:20:2, v/v/v). The drugs separation was achieved using an ACQUITY BEH Shield RP18 column (2.1mm×100mm×1.7µm) in 3min. Under optimized conditions the proposed method was validated in terms of selectivity, linearity, limits of detection (LOD) and quantitation (LOQ), precision and matrix effect, using standard addition calibration. The combination of MEPS and UPLC provides a method for the primary screening of the analytes in 18min with excellent recoveries at three concentration levels, ranging between 80 and 104% (relative standard deviation <11%). The developed methodology has been successfully applied to plasma samples from polydrug abusers.


Assuntos
Psicotrópicos/sangue , Microextração em Fase Sólida/métodos , Drogas Ilícitas/sangue , Detecção do Abuso de Substâncias/métodos , Calibragem , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida , Humanos , Limite de Detecção
18.
Phys Med ; 32(12): 1724-1730, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27856119

RESUMO

Interventional radiology and hemodynamic procedures have rapidly grown in number in the past decade, increasing the importance of personnel dosimetry not only for patients but also for medical staff. The optimization of the absorbed dose during operations is one of the goals that fostered the development of real-time dosimetric systems. Indeed, introducing proper procedure optimization, like correlating dose rate measurements with medical staff position inside the operating room, the absorbed dose could be reduced. Real-time dose measurements would greatly facilitate this task through real-time monitoring and automatic data recording. Besides real-time dose monitoring could allow automatic data recording. In this work, we will describe the calibration and validation of a wireless real-time prototype dosimeter based on a new sensor device (CMOS imager). The validation measurement campaign in clinical conditions has demonstrated the prototype capability of measuring dose-rates with a frequency in the range of few Hz, and an uncertainty smaller than 10%.


Assuntos
Radiologia Intervencionista , Radiometria/métodos , Radiometria/instrumentação , Fatores de Tempo , Tecnologia sem Fio
19.
Front Physiol ; 7: 473, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27833562

RESUMO

Point mutations to the human gene TPM1 have been implicated in the development of both hypertrophic and dilated cardiomyopathies. Such observations have led to studies investigating the link between single residue changes and the biophysical behavior of the tropomyosin molecule. However, the degree to which these molecular perturbations explain the performance of intact sarcomeres containing mutant tropomyosin remains uncertain. Here, we present a modeling approach that integrates various aspects of tropomyosin's molecular properties into a cohesive paradigm representing their impact on muscle function. In particular, we considered the effects of tropomyosin mutations on (1) persistence length, (2) equilibrium between thin filament blocked and closed regulatory states, and (3) the crossbridge duty cycle. After demonstrating the ability of the new model to capture Ca-dependent myofilament responses during both dynamic and steady-state activation, we used it to capture the effects of hypertrophic cardiomyopathy (HCM) related E180G and D175N mutations on skinned myofiber mechanics. Our analysis indicates that the fiber-level effects of the two mutations can be accurately described by a combination of changes to the three tropomyosin properties represented in the model. Subsequently, we used the model to predict mutation effects on muscle twitch. Both mutations led to increased twitch contractility as a consequence of diminished cooperative inhibition between thin filament regulatory units. Overall, simulations suggest that a common twitch phenotype for HCM-linked tropomyosin mutations includes both increased contractility and elevated diastolic tension.

20.
Sci Rep ; 6: 32068, 2016 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-27572147

RESUMO

We have developed an engineered heart tissue (EHT) system that uses laser-cut sheets of decellularized myocardium as scaffolds. This material enables formation of thin muscle strips whose biomechanical characteristics are easily measured and manipulated. To create EHTs, sections of porcine myocardium were laser-cut into ribbon-like shapes, decellularized, and mounted in specialized clips for seeding and culture. Scaffolds were first tested by seeding with neonatal rat ventricular myocytes. EHTs beat synchronously by day five and exhibited robust length-dependent activation by day 21. Fiber orientation within the scaffold affected peak twitch stress, demonstrating its ability to guide cells toward physiologic contractile anisotropy. Scaffold anisotropy also made it possible to probe cellular responses to stretch as a function of fiber angle. Stretch that was aligned with the fiber direction increased expression of brain natriuretic peptide, but off-axis stretches (causing fiber shear) did not. The method also produced robust EHTs from cardiomyocytes derived from human embryonic stem cells and induced pluripotent stem cells (hiPSC). hiPSC-EHTs achieved maximum peak stress of 6.5 mN/mm(2) and twitch kinetics approaching reported values from adult human trabeculae. We conclude that laser-cut EHTs are a viable platform for novel mechanotransduction experiments and characterizing the biomechanical function of patient-derived cardiomyoctyes.


Assuntos
Miocárdio , Engenharia Tecidual/métodos , Tecidos Suporte , Animais , Anisotropia , Técnicas de Cultura de Células/instrumentação , Células Cultivadas , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/fisiologia , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/fisiologia , Lasers de Gás , Mecanotransdução Celular , Contração Miocárdica/efeitos dos fármacos , Miócitos Cardíacos/citologia , Miócitos Cardíacos/fisiologia , Politetrafluoretileno , Ratos , Suínos , Tomografia de Coerência Óptica , Tri-Iodotironina/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA