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Myelofibrosis (MF) is a clonal hematopoietic stem cell disorder classified among chronic myeloproliferative neoplasms, characterized by exacerbated myeloid and megakaryocytic proliferation and bone marrow fibrosis. It is induced by driver (JAK2/CALR/MPL) and high molecular risk mutations coupled to a sustained inflammatory state that contributes to disease pathogenesis. Patient outcome is determined by stratification into risk groups and refinement of current prognostic systems may help individualize treatment decisions. Circulating cell-free (cf)DNA comprises short fragments of double-stranded DNA, which promotes inflammation by stimulating several pathways, including inflammasome activation, which is responsible for IL-1ß and IL-18 maturation and release. In this work, we assessed the contribution of cfDNA as a marker of disease progression and mediator of inflammation in MF. cfDNA was increased in MF patients and higher levels were associated with adverse clinical outcome, a high-risk molecular profile, advanced disease stages and inferior overall survival, indicating its potential value as a prognostic marker. Cell-free DNA levels correlated with tumor burden parameters and markers of systemic inflammation. To mimic the effects of cfDNA, monocytes were stimulated with poly(dA:dT), a synthetic double-stranded DNA. Following stimulation, patient monocytes released higher amounts of inflammasome-processed cytokine, IL-18 to the culture supernatant, reflecting enhanced inflammasome function. Despite overexpression of cytosolic DNA inflammasome sensor AIM2, IL-18 release from MF monocytes was shown to rely mainly on the NLRP3 inflammasome, as it was prevented by NLRP3-specific inhibitor MCC950. Circulating IL-18 levels were increased in MF plasma, reflecting in vivo inflammasome activation, and highlighting the previously unrecognized involvement of this cytokine in MF cytokine network. Monocyte counts were higher in patients and showed a trend towards correlation with IL-18 levels, suggesting monocytes represent a source of circulating IL-18. The close correlation shown between IL-18 and cfDNA levels, together with the finding of enhanced DNA-triggered IL-18 release from monocytes, suggest that cfDNA promotes inflammation, at least in part, through inflammasome activation. This work highlights cfDNA, the inflammasome and IL-18 as additional players in the complex inflammatory circuit that fosters MF progression, potentially providing new therapeutic targets.
Assuntos
Ácidos Nucleicos Livres , Mielofibrose Primária , Humanos , Inflamassomos/metabolismo , Citocinas/metabolismo , Interleucina-18/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Mielofibrose Primária/genética , Inflamação/induzido quimicamente , DNA , Progressão da DoençaRESUMO
While colloidal chemistry provides ways to obtain a great variety of nanoparticles with different shapes, sizes, material compositions, and surface functions, their controlled deposition and combination on arbitrary positions of substrates remain a considerable challenge. Over the last ten years, optical printing arose as a versatile method to achieve this purpose for different kinds of nanoparticles. In this article, we review the state of the art of optical printing of single nanoparticles and discuss its strengths, limitations, and future perspectives by focusing on four main challenges: printing accuracy, resolution, selectivity, and nanoparticle photostability.
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Objectives The quantitation of BCR-ABL1 mRNA is mandatory for chronic myeloid leukemia (CML) patients, and RT-qPCR is the most extensively used method in testing laboratories worldwide. Nevertheless, substantial variation in RT-qPCR results makes inter-laboratory comparability hard. To facilitate inter-laboratory comparative assessment, an international scale (IS) for BCR-ABL1 was proposed. Methods The laboratory-specific conversion factor (CF) to the IS can be derived from the World Health Organization (WHO) genetic reference panel; however, this material is limited to the manufacturers to produce and calibrate secondary reference reagents. Therefore, we developed secondary reference calibrators, as lyophilized cellular material, aligned to the IS. Our purpose was both to re-evaluate the CF in 18 previously harmonized laboratories and to propagate the IS to new laboratories. Results Our field trial including 30 laboratories across Latin America showed that, after correction of raw BCR-ABL1/ABL1 ratios using CF, the relative mean bias was significantly reduced. We also performed a follow-up of participating laboratories by annually revalidating the process; our results support the need for continuous revalidation of CFs. All participating laboratories also received a calibrator to determine the limit of quantification (LOQ); 90% of them could reproducibly detect BCR-ABL1, indicating that these laboratories can report a consistent deep molecular response. In addition, aiming to investigate the variability of BCR-ABL1 measurements across different RNA inputs, we calculated PCR efficiency for each individual assay by using different amounts of RNA. Conclusions In conclusion, for the first time in Latin America, we have successfully organized a harmonization platform for BCR-ABL1 measurement that could be of immediate clinical benefit for monitoring the molecular response of patients in low-resource regions.
Assuntos
Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Calibragem , Humanos , América Latina , Controle de Qualidade , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Padrões de Referência , Reprodutibilidade dos TestesRESUMO
Peruvian women experience high mortality from reproductive cancers, partially due to suboptimal cancer care utilization and experiences. In this qualitative study, we examined factors contributing to positive cancer care experiences. Our sample included 11 cancer patients and 27 cancer providers who attended the First International Cancer Symposium survivorship conference in Lima, Peru in 2015. We conducted thematic analysis. Emergent themes revealed that, for patients, individualized empathic care by providers was an important facilitator to positive cancer care experiences. For providers, the ability to provide such care depended on provider norms and facility infrastructure to support such patient-centered practices.
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Sobreviventes de Câncer/psicologia , Pessoal de Saúde/psicologia , Neoplasias/terapia , Satisfação do Paciente/etnologia , Assistência Centrada no Paciente , Adulto , Idoso , Atitude do Pessoal de Saúde , Empatia , Feminino , Grupos Focais , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Neoplasias/etnologia , Neoplasias/psicologia , Peru , Pesquisa QualitativaRESUMO
Recent national cancer plans address high cancer mortality in Latin America, particularly in Andean countries. Little is known about which individual, interpersonal, and institutional facilitators and barriers persist, particularly from the perspective of cancer survivors. We conducted 15 semi-structured interviews with survivors of breast and cervical cancers during and after a Pan American Health Organization sponsored conference on women's cancers in Lima, Peru. We analyzed data using an inductive content analysis approach. Patients reported primarily psychosocial barriers and facilitators at individual, interpersonal, and institutional levels. Additionally, survivors provided recom-mendations to refine existing policy to improve the cancer care experience for patients.
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Neoplasias da Mama/psicologia , Sobreviventes de Câncer/psicologia , Medo , Conhecimentos, Atitudes e Prática em Saúde , Neoplasias do Colo do Útero/psicologia , Adulto , Idoso , Neoplasias da Mama/etnologia , Feminino , Comportamentos Relacionados com a Saúde , Instalações de Saúde , Acessibilidade aos Serviços de Saúde , Humanos , Entrevistas como Assunto , Pessoa de Meia-Idade , Peru , Pesquisa Qualitativa , Apoio Social , Neoplasias do Colo do Útero/etnologiaRESUMO
Current clinical guidelines for managing chronic myeloid leukemia include molecular monitoring of BCR-ABL1 transcript quantitative reverse-transcription PCR. Despite the proven prognostic significance of molecular response, it is not widely appreciated that quantitative reverse-transcription PCR potentially produces highly variable data, which may affect the validity of results, making comparability between different laboratories difficult. Therefore, standardized reporting of BCR-ABL1 measurements is needed for optimal clinical management. An approach to achieve comparable BCR-ABL1 values is the use of an international reporting scale. Conversion to the international scale is achieved by the application of laboratory specific conversion factor that is obtained by using validated secondary reference calibrators. Moreover, with the aim to mitigate the interlaboratory imprecision of quantitative BCR-ABL1 measurements and to facilitate local laboratory results interpretation and reporting, we decide to prepare laboratory guidelines that will further facilitate interlaboratory comparative studies and independent quality-assessment programs, which are of paramount importance for worldwide standardization of BCR-ABL1 monitoring results, in particular for those most isolated laboratories, with not easy access to commercial kits or sample interchange programs.
Assuntos
Biomarcadores Tumorais/sangue , Proteínas de Fusão bcr-abl/sangue , Genes abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Biomarcadores Tumorais/genética , Guias como Assunto , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Inibidores de Proteínas Quinases/uso terapêutico , Padrões de ReferênciaRESUMO
Actualmente las guías clínicas para el manejo de pacientes con leucemia mieloide crónica incluyen el monitoreo molecular de BCR-ABL1 por PCR cuantitativa en tiempo real; esta metodología permite definir la respuesta molecular. A pesar de la probada importancia pronóstica de la respuesta molecular, en muchos casos no se tiene en cuenta que la PCR cuantitativa puede producir datos muy variables, que pueden afectar la validez de los resultados, y hacer difícil la comparación entre diferentes laboratorios. Por lo tanto, para un manejo clínico óptimo, es absolutamente necesaria la estandarización de las metodologías de medición de BCR-ABL1. La estrategia para obtener valores de BCR-ABL1 comparables consiste en la adopción de la escala internacional. La conversión a la escala internacional se logra mediante la aplicación de un factor de conversión específico para cada laboratorio; este factor de conversión se puede obtener mediante el uso de calibradores secundarios validados, que hoy se producen en Argentina, en el marco del programa nacional de armonización. Por otra parte, con el objetivo de mitigar las diferencias entre laboratorios y facilitar criterios uniformes en la interpretación de los resultados y presentación de los informes, decidimos preparar estas guías de laboratorio. Esto permitirá además a los laboratorios poder evaluar su calidad de trabajo, tarea muy importante, en particular para aquellos centros más aislados, que no tienen fácil acceso a costosos kits comerciales o programas internacionales de intercambio de muestras.
Current clinical guidelines for managing chronic myeloid leukemia include molecular monitoring of BCR-ABL1 transcript quantitative reverse-transcription PCR. Despite the proven prognostic significance of molecular response, it is not widely appreciated that quantitative reverse-transcription PCR potentially produces highly variable data, which may affect the validity of results, making comparability between different laboratories difficult. Therefore, standardized reporting of BCR-ABL1 measurements is needed for optimal clinical management. An approach to achieve comparable BCR-ABL1 values is the use of an international reporting scale. Conversion to the international scale is achieved by the application of laboratory specific conversion factor that is obtained by using validated secondary reference calibrators. Moreover, with the aim to mitigate the interlaboratory imprecision of quantitative BCR-ABL1 measurements and to facilitate local laboratory results interpretation and reporting, we decide to prepare laboratory guidelines that will further facilitate interlaboratory comparative studies and independent quality-assessment programs, which are of paramount importance for worldwide standardization of BCR-ABL1 monitoring results, in particular for those most isolated laboratories, with not easy access to commercial kits or sample interchange programs.
Assuntos
Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Biomarcadores Tumorais/sangue , Genes abl/genética , Proteínas de Fusão bcr-abl/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Padrões de Referência , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Biomarcadores Tumorais/genética , Guias como Assunto , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
BACKGROUND: Anagrelide represents a treatment option for essential thrombocythemia, although its place in therapy remains controversial. AIM: To assess the impact of mutational status in response rates and development of adverse events during long-term use of anagrelide. METHODS: We retrospectively evaluated 67 patients with essential thrombocythemia treated with anagrelide during 68 (4-176) months. RESULTS: Mutational frequencies were 46.3%, 28.3%, and 1.5% for JAK2V617F, CALR and MPL mutations. Anagrelide yielded a high rate of hematologic responses, which were complete in 49.25% and partial in 46.25%, without differences among molecular subsets. The rate of thrombosis during treatment was one per 100 patient-years, without excess bleeding. Anemia was the major adverse event, 30.3% at 5-yr follow-up, being more frequent in CALR(+) (P < 0.05). Myelofibrotic transformation developed in 14.9% (12.9%, 21%, and 12.5% in JAK2V617F(+), CALR(+), and triple-negative patients, respectively, P = NS) and those treated >60 months were at higher risk, OR (95% CI) 9.32 (1.1-78.5), P < 0.01, indicating the need for bone marrow monitoring during prolonged treatment. CONCLUSION: Although CALR(+) patients were at higher risk of developing anemia, anagrelide proved effective among all molecular subsets, indicating that mutational status does not seem to represent a major determinant of choice of cytoreductive treatment among essential thrombocythemia therapies.
Assuntos
Calreticulina/genética , Janus Quinase 2/genética , Inibidores da Agregação Plaquetária/administração & dosagem , Quinazolinas/administração & dosagem , Receptores de Trombopoetina/genética , Trombocitemia Essencial/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/etiologia , Anemia/patologia , Calreticulina/imunologia , Criança , Feminino , Seguimentos , Expressão Gênica , Humanos , Janus Quinase 2/imunologia , Masculino , Pessoa de Meia-Idade , Mutação , Inibidores da Agregação Plaquetária/efeitos adversos , Mielofibrose Primária/etiologia , Mielofibrose Primária/patologia , Quinazolinas/efeitos adversos , Receptores de Trombopoetina/imunologia , Estudos Retrospectivos , Trombocitemia Essencial/genética , Trombocitemia Essencial/imunologia , Trombocitemia Essencial/patologiaRESUMO
Epstein Barr virus (EBV) sequence variation is thought to contribute to Burkitt lymphoma (BL), but lack of data from primary BL tumors hampers efforts to test this hypothesis. We directly sequenced EBV from 12 BL biopsies from Ghana, Brazil, and Argentina, aligned the obtained reads to the wild-type (WT) EBV reference sequence, and compared them with 100 published EBV genomes from normal and diseased people from around the world. The 12 BL EBVs were Type 1. Eleven clustered close to each other and to EBV from Raji BL cell line, but away from 12 EBVs reported from other BL-derived cell lines and away from EBV from NPC and healthy people from Asia. We discovered 23 shared novel nucleotide-base changes in the latent membrane protein (LMP)-1 promoter and gene (associated with 9 novel amino acid changes in the LMP-1 protein) of the 11 BL EBVs. Alignment of this region for the 112 EBV genomes revealed four distinct patterns, tentatively termed patterns A to D. The distribution of BL EBVs was 48%, 8%, 24% and 20% for patterns A to D, respectively; the NPC EBV's were Pattern B, and EBV-WT was pattern D. Further work is needed to investigate the association between EBV LMP-1 patterns with BL.
Assuntos
Linfoma de Burkitt/virologia , Infecções por Vírus Epstein-Barr/virologia , Regulação Viral da Expressão Gênica , Genoma Viral , Herpesvirus Humano 4/genética , Proteínas da Matriz Viral/genética , África , Sequência de Aminoácidos , Biópsia , Linfoma de Burkitt/etiologia , Linfoma de Burkitt/patologia , Criança , Pré-Escolar , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/patologia , Feminino , Variação Genética , Genótipo , Herpesvirus Humano 4/patogenicidade , Humanos , Masculino , Dados de Sequência Molecular , Filogenia , Regiões Promotoras Genéticas , Alinhamento de Sequência , Análise de Sequência de DNA , América do SulAssuntos
Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Pediatria , Síndrome , Anormalidades Congênitas , Ilustração MédicaRESUMO
In this work we present a method that enables simultaneous measurement of shape and wall parameters of glass containers. The system is based on the optical coherence tomography technique, employing the spectral domain configuration. The data were obtained by measuring the spatial coordinates of a sequence of points in a predefined region of a sample that includes points on the surface and in the interior of the material. Dimensional parameters, thickness mapping, and tomography studies of the interior of the sample walls can be obtained from these measurements.
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La determinación de la carga viral de HIV y la detección del ADN proviral en semen se utilizan en protocolos de fertilización para parejas discordantes (hombre HIV positivo - mujer AMPLICOR HIV-1 MONITOR tm Test versión 1.5 (Roche) en plasma seminal para estimar la carga viral. Se procesaron 31 muestras de plasma seminal, diluidas y sin diluir para evaluar la amplificación del control interno y descartar posibles inhibiciones. Luego se contaminaron 22 muestras con plasma de pacientes HIV positivos para verificar la cuantificación del ARN viral. Finalmente, se procesaron 12 muestras en paralelo por Nuclisens HIV-1 QT (Biomerieux) para descartar potenciales falsos negativos. Concluimos que el sistema evaluado es un método adecuado para cuantificar ARN viral en plasma seminal. No se observó inhibición, ni falsos negativos y los valores de carga viral y el límite de detección no se vieron modificados por la matriz diferente.
Analyses of the HIV load and presence of proviral DNA in sperm samples are used in assisted fertilization protocols for discordant couples (infected man-healthy woman). We evaluated the use of the COBAS Ampliprep/COBAS AMPLICOR HIV-1 MONITOR tm Test versión 1.5 (Roche) for viral load quantification in seminal plasma samples. We first tested 31 sperm samples for amplification of the internal control to discard potential inhibition. Seminal plasmas were analyzed directly and diluted. We then spiked 21 sperm samples with human plasma from HIV-positive patients to confirm that HIV RNA could be amplified. We also compared the results of 12 samples with NASBA (Nuclisens HIV-1 QT, Biomerieux), and confirmed lack of false negative results. We conclude that the new assay is an adequate methodology to analyze HIV load in sperm samples. We did not observed inhibition, neither false negative results and quantification demonstrated equivalent HIV loads.
Assuntos
Humanos , Masculino , Terapia Antirretroviral de Alta Atividade , DNA , Fertilização/imunologia , HIV , Guias como Assunto/métodos , Inibidores da Transcriptase Reversa , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sêmen/imunologia , Técnicas de Amplificação de Ácido Nucleico/métodos , Carga ViralRESUMO
La determinación de la carga viral de HIV y la detección del ADN proviral en semen se utilizan en protocolos de fertilización para parejas discordantes (hombre HIV positivo - mujer AMPLICOR HIV-1 MONITOR tm Test versión 1.5 (Roche) en plasma seminal para estimar la carga viral. Se procesaron 31 muestras de plasma seminal, diluidas y sin diluir para evaluar la amplificación del control interno y descartar posibles inhibiciones. Luego se contaminaron 22 muestras con plasma de pacientes HIV positivos para verificar la cuantificación del ARN viral. Finalmente, se procesaron 12 muestras en paralelo por Nuclisens HIV-1 QT (Biomerieux) para descartar potenciales falsos negativos. Concluimos que el sistema evaluado es un método adecuado para cuantificar ARN viral en plasma seminal. No se observó inhibición, ni falsos negativos y los valores de carga viral y el límite de detección no se vieron modificados por la matriz diferente.(AU)
Analyses of the HIV load and presence of proviral DNA in sperm samples are used in assisted fertilization protocols for discordant couples (infected man-healthy woman). We evaluated the use of the COBAS Ampliprep/COBAS AMPLICOR HIV-1 MONITOR tm Test versión 1.5 (Roche) for viral load quantification in seminal plasma samples. We first tested 31 sperm samples for amplification of the internal control to discard potential inhibition. Seminal plasmas were analyzed directly and diluted. We then spiked 21 sperm samples with human plasma from HIV-positive patients to confirm that HIV RNA could be amplified. We also compared the results of 12 samples with NASBA (Nuclisens HIV-1 QT, Biomerieux), and confirmed lack of false negative results. We conclude that the new assay is an adequate methodology to analyze HIV load in sperm samples. We did not observed inhibition, neither false negative results and quantification demonstrated equivalent HIV loads.(AU)
Assuntos
Humanos , Masculino , HIV/imunologia , Carga Viral , DNA/análise , Fertilização/imunologia , Guias como Assunto/métodos , Sêmen/imunologia , Terapia Antirretroviral de Alta Atividade , Técnicas de Amplificação de Ácido Nucleico/métodos , Inibidores da Transcriptase Reversa , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Epstein-Barr virus genotypes can be distinguished by polymorphic variations in the genes encoding EBNA2, 3A, 3B, and 3C. The immediate early gene BZLF1 plays a key role in modulating the switch from latency to lytic replication and therefore enabling viral propagation. The aim of this study was to investigate and compare BZLF1 promoter sequence (Zp) variation in pediatric infectious mononucleosis (IM) and in pediatric EBV positive lymphoma biopsies. Zp was sequenced from peripheral blood mononuclear cells (PBMC) and throat swabs from 10 patients with IM at the time of diagnosis (D0) and during convalescence; and from 13 lymphoma biopsies. Zp - P and Zp - V3 variants were found in eight and one IM patients, as well as in five and six tumor biopsies, respectively. A correlation between viral genotype and Zp variant was found significant for Zp - V3 and EBV2 (P = 0.0002). One IM patient harbored two concomitant Zp variants. Regardless of anatomical compartment or stage of disease all IM patients displayed the same Zp variant along the course of the study. No new infections or adaptative selection of different variants was evidenced. A new Zp variant (Zp - V3 + 49) was described in two Hodgkin lymphomas, but not in IM. This is the first study to describe Zp variants compartmentalization in children with acute EBV infection and convalescence in a developing country; and comparing them with Zp variants in pediatric lymphomas from the same geographic area.
Assuntos
Herpesvirus Humano 4/genética , Mononucleose Infecciosa/virologia , Linfoma/virologia , Polimorfismo Genético , Regiões Promotoras Genéticas , Transativadores/genética , Adolescente , Biópsia , Criança , Pré-Escolar , Feminino , Genótipo , Herpesvirus Humano 4/isolamento & purificação , Humanos , Leucócitos Mononucleares/virologia , Masculino , Dados de Sequência Molecular , Faringe/virologia , Análise de Sequência de DNARESUMO
El Crosslinking corresponde a la generación de nuevos enlaces entre las cadenas colágenas del estroma anterior corneal mediante fotomediador, la riboflavina y la irradiación con luz UV-A. La aplicación del CXL da a lugar a la aparición de una nueva proteína colágena remarcablemente estable, resistente a la desnaturalización por calor, mercaptoetanol y pepsina, con un diámetro aumentado y mayor fuerza tensil. El proceso da a lugar a una cornea con mayor resistencia al estiramiento, incrementando la estabilidad mecánica y bioquímica del tejido corneal, deteniendo el curso natural de patologías corneales progresivas. Además, se asocia a una mejoría en la agudeza visual de los pacientes tratados con y sin corrección especialmente apreciable a partir del tercer mes postoperatorio. Estas mejorías pueden ser modestas y no encontrarse en todos los casos. La indicación principal del CXL corresponde a los queratoconos iniciales (tipo 1 y 2 de la clasificación de Krumeich) y aquellos que hayan sufrido empeoramiento en los últimos seis meses. Es también útil en la cirugía corneal refractiva para el tratamiento de la queractasia iatrogénica del LASIK (láser in situ keratomileusis). Una nueva aplicación corresponde a la terapia de los meltings corneales por queratitis microbianas no respondedoras al tratamiento medico. El principal efecto secundario advertido, ha sido el edema (opacidad) estromaltransitorio o haze, con aparición entre los tres y seis meses manejado exitosamente dexametasona tópica por un mes. La presencia de prominentes estrías de Vogt preoperatorias y de microestrías hipodensas a la microscopia confocal especialmente aquellas con patrón reticular con o sin estrías de Vogt (el patrón reticular podría representar un signo de queratocono avanzado) se postulan como una posible causa de opacidad corneal post operatoria y cicatrices estromales tardías. En pacientes con ectasia post LASIK, el CXL se puede asociar a queratitis difusa lamelar...
Assuntos
Substância Própria , Ceratite , Acuidade VisualRESUMO
El Crosslinking corresponde a la generación de nuevos enlaces entre las cadenas colágenas del estroma anterior corneal mediante fotomediador, la riboflavina y la irradiación con luz UV-A. La aplicación del CXL da a lugar a la aparición de una nueva proteína colágena remarcablemente estable, resistente a la desnaturalización por calor, mercaptoetanol y pepsina, con un diámetro aumentado y mayor fuerza tensil. El proceso da a lugar a una cornea con mayor resistencia al estiramiento, incrementando la estabilidad mecánica y bioquímica del tejido corneal, deteniendo el curso natural de patologías corneales progresivas. Además, se asocia a una mejoría en la agudeza visual de los pacientes tratados con y sin corrección especialmente apreciable a partir del tercer mes postoperatorio. Estas mejorías pueden ser modestas y no encontrarse en todos los casos. La indicación principal del CXL corresponde a los queratoconos iniciales (tipo 1 y 2 de la clasificación de Krumeich) y aquellos que hayan sufrido empeoramiento en los últimos seis meses. Es también útil en la cirugía corneal refractiva para el tratamiento de la queractasia iatrogénica del LASIK (láser in situ keratomileusis). Una nueva aplicación corresponde a la terapia de los meltings corneales por queratitis microbianas no respondedoras al tratamiento medico. El principal efecto secundario advertido, ha sido el edema (opacidad) estromaltransitorio o haze, con aparición entre los tres y seis meses manejado exitosamente dexametasona tópica por un mes. La presencia de prominentes estrías de Vogt preoperatorias y de microestrías hipodensas a la microscopia confocal especialmente aquellas con patrón reticular con o sin estrías de Vogt (el patrón reticular podría representar un signo de queratocono avanzado) se postulan como una posible causa de opacidad corneal post operatoria y cicatrices estromales tardías. En pacientes con ectasia post LASIK, el CXL se puede asociar a queratitis difusa lamelar...(AU)
Assuntos
Substância Própria , Acuidade Visual , CeratiteRESUMO
The putative tumor-suppressor gene p16 was mapped to human chromosome 9p21, close to the interferon alpha cluster. The frequency and association of gene alterations of p16, interferon alpha and interferon beta were investigated in a total of 39 Acute Lymphoblastic Leukemia (ALL) patients. Of these, 10 patients (25.6 per cent) presented abnormalities of at least one of the three genes studied. In 32 ALL cases studies of the three genes could be accomplished. In 23 out of 32 ALL cases the 3 genes studied were normally preserved. In the remaining 9 ALL, p16 was affected in 8 cases by homozygous deletions. In 2 patients, p16 deletion was associated with homozygous deletions for interferon alpha and interferon beta genes and in 1 case with total deletion of interferon beta 1 gene and partial deletion of interferon alpha. In the remaining 5 cases, p16 was the only gene deleted with no alteration of type interferon genes. These data indicate that p16 gene is deleted in a higher frequency than type I interferon genes in ALL. Moreover, within the ALL group with p16 gene deletion, 37.5 per cent are associated with interferon deletions and in general, ALL with alpha and/or beta interferon gene deletions are associated with p16 deletions. Therefore, p16 gene deletion with preserved type I interferon genes in some ALL suggests that the absence of this cdk inhibitor may disturb the normal cell cycle and favor blast transformation.