RESUMO
OBJECTIVE: To investigate electrically evoked auditory cortical responses (eACR) elicited from the stimulation of intracochlear electrodes based on individually fitted stimulation parameters in cochlear implant (CI) users. DESIGN: An eACR setup based on individual fitting parameters is proposed. A 50-ms alternating biphasic pulse train was used to stimulate apical, medial, and basal electrodes and to evoke auditory cortical potentials (N1-P2 complex). STUDY SAMPLE: The eACR setup proposed was validated with 14 adult CI users. RESULTS: Individual and grand-average eACR waveforms were obtained. The eACR amplitudes were lower in the basal than in the apical and medial regions. Earlier N1 latencies were found in CI users with lower maximum comfortable loudness levels and shorter phase duration in response to apical stimulation, while medial and basal stimulation resulted in earlier N1 latencies and larger N1-P2 amplitudes in users with longer CI experience. CONCLUSIONS: eACR could be elicited by direct intracochlear stimulation using individual fitting parameters with a success rate of 71%. The highest cortical peak-to-peak amplitudes were obtained in response to apical stimulation. Unlike the P2, the N1 component appeared to be a consistent cortical potential to determine eACR and gain knowledge of the auditory processing beyond the cochlea in CI users. HighlightseACR can be elicited through direct stimulation of intracochlear electrodes.Stimulation of apical and medial regions yielded the highest N1-P2 amplitudes.CI users with lower maximum comfortable loudness levels had shorter N1 latencies during apical stimulation.The present dataset of mainly well-performing CI users suggests better cortical processing, that is, higher amplitudes and shorter latencies of N1.The N1 potential appears a more consistent and reliable potential than the P2 to determine eACR responses in CI users.
Assuntos
Implante Coclear , Implantes Cocleares , Adulto , Humanos , Potenciais Evocados Auditivos/fisiologia , Cóclea , Percepção Auditiva/fisiologia , Estimulação ElétricaRESUMO
INTRODUCTION: Patient-reported outcomes (PROs) use, via a computer registry, allows patients to report their symptoms enabling the detection of early signs of progression of the disease. For such a record, the patient needs to show certain skills in new technologies use. The present study aimed to analyse the perception and degree of digital literacy of patients undergoing oncological treatment in an Oncology Day Hospital (ODH). METHODS: A cross-sectional descriptive study was performed, where the degree of literacy of patients attending antineoplastic treatment at the ODH was examined by means of an anonymous survey. RESULTS: A total of 122 patients have been included in the study. The proportion of subjects who use the electronic mail (TM) and the Internet on a daily basis was 45.1% and 70.5%, respectively, and up to 77.9% from the subjects considered that the use of digital 2.0 strategies could help improve communication between healthcare professional and patient.The TM was determined by the age, educational level and employment status of the individual. Furthermore, the age of the patients conditioned their perception of the usefulness of the web 2.0 tools (T2.0). CONCLUSION: This study allowed us to establish a target patient profile to conduct the efficient monitoring of cancer progression by PROs. The results have shown that approximately 60% of the patients in our population could be potential candidates to receive PROs-based health care. This approach enables earlier detection of symptoms and signs of progression and consequently, improves health outcomes for cancer patients.
Assuntos
Alfabetização , Medidas de Resultados Relatados pelo Paciente , Estudos Transversais , Unidades Hospitalares , Humanos , Inquéritos e QuestionáriosRESUMO
Asparaginase (ASNase) use as a tumour-inhibitor drug has changed completely the natural course of paediatric acute lymphoblastic leukaemia (ALL) in such a way that it represents a paradigm shift in ALL management. ASNase treatment emergence has significantly improved pathologic responses and increased survival rates of ALL patients. Although different ASNase forms are currently available, only the pegylated form (PEG-ASNase) is recommended by relevant clinic guides. PEG-ASNase form shows longer elimination half-life, reducing the number of administrations, along with an enhanced safety profile. In spite of all of these advantages, PEG-ASNase elevated cost limits enormously its use. PEG-ASNase is commercialised as a lyophilised powder which according to the manufacturer it is stable for 24 hours once reconstituted, as a result, the leftover is usually discarded. In this study we analysed the enzymatic stability of reconstituted PEG-ASNase after conservation in three different temperature conditions for 5 and 14 days, aiming to take advantage of the remaining leftover for the subsequent administration. Our results have shown that PEG-ASNase is stable at 4°C, -20°C and -80°C for at least 14 days, retaining the 95% from the initial enzymatic activity in all three storage temperatures. According to our results, it is feasible to reuse the remaining content of PEG-ASNase vial after reconstitution, which means a 50% reduction of its cost for paediatric patient treatment and, consequently, removes the main barrier to use this drug in a wider population.
Assuntos
Asparaginase/química , Polietilenoglicóis/química , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Estabilidade Enzimática , Liofilização , Humanos , TemperaturaRESUMO
Tuberculosis (TB) is one of the world's most pernicious diseases mainly due to immune evasion strategies displayed by its causative agent Mycobacterium tuberculosis (Mtb). Blood monocytes (Mos) represent an important source of DCs during chronic infections; consequently, the alteration of their differentiation constitutes an escape mechanism leading to mycobacterial persistence. We evaluated whether the CD16(+)/CD16(-) Mo ratio could be associated with the impaired Mo differentiation into DCs found in TB patients. The phenotype and ability to stimulate Mtb-specific memory clones DCs from isolated Mo subsets were assessed. We found that CD16(-) Mos differentiated into CD1a(+) DC-SIGN(high) cells achieving an efficient recall response, while CD16(+) Mos differentiated into a CD1a(-) DC-SIGN(low) population characterized by a poor mycobacterial Ag-presenting capacity. The high and sustained phosphorylated p38 expression observed in CD16(+) Mos was involved in the altered DC profile given that its blockage restored DC phenotype and its activation impaired CD16(-) Mo differentiation. Furthermore, depletion of CD16(+) Mos indeed improved the differentiation of Mos from TB patients toward CD1a(+) DC-SIGN(high) DCs. Therefore, Mos from TB patients are less prone to differentiate into DCs due to their increased proportion of CD16(+) Mos, suggesting that during Mtb infection Mo subsets may have different fates after entering the lungs.
Assuntos
Células Dendríticas/patologia , Monócitos/patologia , Receptores de IgG/metabolismo , Tuberculose/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Adulto , Antígenos CD1/imunologia , Antígenos CD1/metabolismo , Diferenciação Celular/imunologia , Células Dendríticas/enzimologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Feminino , Proteínas Ligadas por GPI/imunologia , Proteínas Ligadas por GPI/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Monócitos/enzimologia , Monócitos/imunologia , Monócitos/metabolismo , Mycobacterium tuberculosis/imunologia , Receptores de IgG/imunologia , Transdução de Sinais/imunologia , Transdução de Sinais/fisiologia , Tuberculose/enzimologia , Tuberculose/metabolismo , Tuberculose/microbiologia , Adulto Jovem , Proteínas Quinases p38 Ativadas por Mitógeno/imunologiaRESUMO
Tuberculosis pathogenesis was earlier thought to be mainly related to the host but now it appears to be clear that bacterial factors are also involved. Genetic variability of Mycobacterium tuberculosis (Mtb) could be slight but it may lead to sharp phenotypic differences. We have previously reported that nonopsonized Mtb H37Rv induce apoptosis of polymorphonuclear neutrophils (PMNs) by a mechanism that involves the p38 pathway. Here we evaluated the capability to induce PMN apoptosis of two prevalent Mtb lineages in Argentina, the Latin America and Mediterranean (LAM), and Haarlem, using the H37Rv as a reference strain. Results showed that LAM strains strongly induced apoptosis of PMN which correlated with the induction of reactive oxygen species (ROS) production and p38 activation. Interestingly, the highly prosperous multidrug-resistant M strain, belonging to the Haarlem lineage, lacked the ability to activate and to induce PMN apoptosis as a consequence of (1) a weak ROS production and (2) the contribution of antiapoptotic mechanisms mediated at least by ERK. Although with less skill, M is able to enter the PMN so that phenotypic differences could lead PMN to be a reservoir allowing some pathogens to prevail and persist over other strains in the community.
Assuntos
Apoptose/imunologia , Mycobacterium tuberculosis/imunologia , Neutrófilos/imunologia , Explosão Respiratória/imunologia , Antígenos CD/metabolismo , Antígeno CD11b/metabolismo , Moléculas de Adesão Celular/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas Ligadas por GPI/metabolismo , Humanos , Mycobacterium tuberculosis/isolamento & purificação , Neutrófilos/metabolismo , Neutrófilos/microbiologia , Fagocitose/imunologia , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
BACKGROUND: The proinflammatory cytokine interleukin 17 (IL-17) plays an important role in immune responses but it is also associated with tissue-damaging inflammation. So, we evaluated the ability of Mycobacterium tuberculosis clinical isolates to induce IL-17 in tuberculosis (TB) patients and in healthy human tuberculin reactors (PPD(+)HD). METHODS: IL-17, interferon γ (IFN-γ), and interleukin 23 (IL-23) receptor expression were evaluated ex vivo and cultured peripheral blood mononuclear cells from TB and PPD(+)HD stimulated with irradiated clinical isolates from multidrug resistant (MDR) outbreaks M (Haarlem family) and Ra (Latin American-Mediterranean family), as well as drug-susceptible isolates belonging to the same families and laboratory strain H37Rv for 48 hours in T-cell subsets by flow cytometry. RESULTS: We observed that: (1) MDR strains M and Ra are stronger IL-17 inducers than drug-susceptible Mtb strains of the Haarlem and Latin American-Mediterranean families, (2) MDR-TB patients show the highest IL-17 expression that is independent on the strain, (3) IL-17 expression is dependent on CD4(+) and CD8(+) T cells associates with persistently high antigen load. CONCLUSIONS: IL-17--producing T cells could play an immunopathological role in MDR-TB promoting severe tissue damage, which may be associated with the low effectiveness of the second-line drugs employed in the treatment.
Assuntos
Antígenos de Bactérias/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Mycobacterium tuberculosis/imunologia , Subpopulações de Linfócitos T/imunologia , Tuberculose Resistente a Múltiplos Medicamentos/imunologia , Adulto , Células Cultivadas , Feminino , Humanos , Interferon gama/metabolismo , Interleucina-17/metabolismo , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Receptores de Interleucina/metabolismo , Subpopulações de Linfócitos T/metabolismo , Adulto JovemRESUMO
Tuberculous pleurisy, one of the most common manifestations of extrapulmonary tuberculosis, is characterized by a T-cell-mediated hypersensitivity reaction along with a Th1 immune profile. In this study, we investigated functional cross-talk among T and NK cells in human tuberculous pleurisy. We found that endogenously activated pleural fluid-derived NK cells express high ICAM-1 levels and induce T-cell activation ex vivo through ICAM-1. Besides, upon in vitro stimulation with monokines and PAMP, resting peripheral blood NK cells increased ICAM-1 expression leading to cellular activation and Th1 polarization of autologous T cells. Furthermore, these effects were abolished by anti-ICAM-1 Ab. Hence, NK cells may contribute to the adaptive immune response by a direct cell-contact-dependent mechanism in the context of Mycobacterium tuberculosis infection.
Assuntos
Molécula 1 de Adesão Intercelular/metabolismo , Células Matadoras Naturais/imunologia , Mycobacterium tuberculosis , Linfócitos T/imunologia , Tuberculose Pleural/imunologia , Adulto , Antígeno CD11a/imunologia , Antígeno CD56/imunologia , Comunicação Celular/imunologia , Cisteína/análogos & derivados , Cisteína/farmacologia , Humanos , Molécula 1 de Adesão Intercelular/efeitos dos fármacos , Molécula 1 de Adesão Intercelular/imunologia , Interleucina-12/farmacologia , Interleucina-15/farmacologia , Interleucina-18/farmacologia , Lipopolissacarídeos/farmacologia , Lipoproteínas/farmacologia , Pessoa de Meia-Idade , Fosfotransferases (Aceptor do Grupo Fosfato)RESUMO
The role of CD16(-) and CD16(+) Mo subsets in human TB remains unknown. Our aim was to characterize Mo subsets from TB patients and to assess whether the inflammatory milieu from TB pleurisy modulate their phenotype and recruitment. We found an expansion of peripheral CD16(+) Mo that correlated with disease severity and with TNF-α plasma levels. Circulating Mo from TB patients are activated, showing a higher CD14, CD16, and CD11b expression and Mtb binding than HS. Both subsets coexpressed CCR2/CCR5, showing a potential ability to migrate to the inflammatory site. In tuberculous PF, the CD16(+) subset was the main Mo/MΦ population, accumulation that can be favored by the induction of CD16 expression in CD16(-) Mo triggered by soluble factors found in this inflammatory milieu. CD16(+) Mo in PF were characterized by a high density of receptors for Mtb recognition (DC-SIGN, MR, CD11b) and for lipid-antigens presentation (CD1b), allowing them to induce a successful, specific T cell proliferation response. Hence, in tuberculous PF, CD16(+) Mo constitute the main APC population; whereas in PB, their predominance is associated with the severity of pulmonary TB, suggesting a paradoxical role of the CD16(+) Mo subset that depends on the cellular localization.
Assuntos
Monócitos/imunologia , Receptores CCR2/análise , Receptores CCR5/análise , Receptores de IgG/análise , Tuberculose Pleural/imunologia , Tuberculose/imunologia , Adulto , Idoso , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/metabolismo , Separação Celular , Citocinas/análise , Citocinas/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Proteínas Ligadas por GPI/análise , Proteínas Ligadas por GPI/imunologia , Proteínas Ligadas por GPI/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Derrame Pleural/imunologia , Derrame Pleural/metabolismo , Receptores CCR2/imunologia , Receptores CCR2/metabolismo , Receptores CCR5/imunologia , Receptores CCR5/metabolismo , Receptores de IgG/imunologia , Receptores de IgG/metabolismo , Tuberculose/metabolismo , Tuberculose Pleural/metabolismoRESUMO
BACKGROUND: Although invasive management of ST segment elevation myocardial infarction has improved the clinical outcome, cardiogenic shock (CS) remains an important issue. Our purpose was to asses the utility of the initial electrocardiogram in detecting patients who are at increased risk of CS after percutaneous coronary intervention for acute myocardial infarction. METHODS: We evaluated 508 consecutive patients admitted in our Coronary Unit and treated by primary angioplasty within 12 h of an ST segment elevation myocardial infarction. Patients with cardiogenic shock at admission were excluded. Two groups were defined according to the presence of distortion of the terminal portion of the QRS in two or more adjacent leads (group 1) or the absence of this pattern (group 2). RESULTS: There were 99 patients (20%) in group 1 and 409 (80%) in group 2. CS developed in 38 patients, 18 in group 1 (18%) and 20 in group 2 (5%), p<0.001. Seventeen patients died in hospital, 6 in group 1 (6%) and 11 in group 2 (3%), p 0.094. Multivariate analysis including clinical, electrocardiographic and angiographic variables showed distortion of the QRS as an independent predictor of cardiogenic shock (odds ratio 3.17, 95% confidence interval 1.44 to 6.96, p 0.004), together with Killip class at admission and TIMI 3 flow after revascularization. CONCLUSIONS: Distortion of the terminal portion of the QRS complex is a strong predictor of cardiogenic shock in STEMI patients. Close hemodynamic monitoring should be warranted in patients showing this electrocardiographic pattern.