RESUMEN
Early post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) relapse in patients with acute myeloid leukemia (AML) has an almost invariably dismal prognosis. Recent studies have demonstrated that FLT3 inhibition enhances the graft-versus-leukemia effect in vitro and in vivo. Thus, FLT-3 inhibitors may be viable treatment options in this setting. Here, we report three patients with FLT3 and NPM1 mutated AML who relapsed early after allo-HSCT and were treated with gilteritinib (associated with donor lymphocyte Infusion in two patients) to achieve long-term remission without a second transplantation.
RESUMEN
Combined therapy with venetoclax and hypomethylating agents has significantly improved the outcome of unfit patients ineligible for intensive chemotherapy. A recently published exploratory analysis of the VIALE-A trial reported that up to 51% of patients achieving remission survived more than 2 years. These data along with those from reallife settings, lead to questioning how long it is appropriate to continue treatment in long-term survivors. Accordingly, recent retrospective studies suggested the feasibility of suspending therapy in selected patients while maintaining prolonged responses. Also, these studies showed that retreatment may induce a second remission in almost a third of patients. We report the case of a patient who received salvage therapy with venetoclax and azacytidine, that was discontinued few cycles after blasts clearance because of severe hematological toxicity. Despite suspension, he maintained a sustained response lasting almost one year and was successfully retreated with the same combination when a second relapse occurred.
RESUMEN
Two separate goals should be jointly pursued in wastewater treatment: nutrient removal and energy conservation. An efficient controller performance should cope with process uncertainties, seasonal variations and process nonlinearities. This paper describes the design and testing of a model predictive controller (MPC) based on neuro-fuzzy techniques that is capable of estimating the main process variables and providing the right amount of aeration to achieve an efficient and economical operation. This algorithm has been field tested on a large-scale municipal wastewater treatment plant of about 500,000 PE, with encouraging results in terms of better effluent quality and energy savings.
Asunto(s)
Eliminación de Residuos Líquidos , Aguas Residuales , Algoritmos , Aprendizaje AutomáticoRESUMEN
In the present work, 19 Mycobacterium bovis isolates from different cats were typified by spoligotyping. We detected nine spoligotypes. There was only one cluster, which grouped 11 of the isolates (57.9%), showing the main spoligotype from cattle from Argentina. The rest of the spoligotypes presented only one isolate each. Five of them were not found in cattle, and were unique and exclusive of cats. The isolates studied show that tuberculosis of bovine origin in cats constitutes a potential public health problem in Buenos Aires region. The identification of genotypes from non-natural hosts could contribute to understand the spread of bovine tuberculosis. This is the first report showing genetic profiles of M. bovis isolates in felines from Argentina.
En el presente trabajo se tipificaron por spoligotyping 19 aislamientos de M. bovis de diferentes gatos. Se detectaron 9 espoligotipos y un único agrupamiento o cluster integrado por 11 aislamientos (57,9%) y relacionado con el principal espoligotipo de bovinos de Argentina. El resto de los espoligotipos detectados presentaron solamente un aislamiento cada uno; 5 de ellos no se encontraron en bovinos y fueron únicos y exclusivos de gatos. La presencia de estos aislamientos indica que la tuberculosis bovina en los gatos constituye un potencial problema de salud pública en la ciudad de Buenos Aires. La identificación de genotipos de aislamientos de M. bovis de hospedadores no convencionales podría contribuir a la mejor comprensión de la diseminación de la tuberculosis bovina. Este es el primer informe en el que se muestran los perfiles genotípicos de aislamientos de M. bovis obtenidos de felinos de Argentina.
Asunto(s)
Animales , Bovinos , Técnicas de Tipificación Bacteriana/métodos , Enfermedades de los Gatos/microbiología , Gatos/microbiología , ADN Bacteriano/análisis , Mycobacterium bovis/aislamiento & purificación , Reacción en Cadena de la Polimerasa/métodos , Tuberculosis/veterinaria , Alimentación Animal/efectos adversos , Alimentación Animal/microbiología , Argentina/epidemiología , Enfermedades de los Gatos/epidemiología , Enfermedades de los Gatos/transmisión , ADN Bacteriano/genética , Reservorios de Enfermedades/microbiología , Reservorios de Enfermedades/veterinaria , Contaminación de Alimentos , Microbiología de Alimentos , Pulmón/microbiología , Mycobacterium bovis/clasificación , Mycobacterium bovis/genética , Tuberculosis Bovina/epidemiología , Tuberculosis Bovina/microbiología , Tuberculosis Bovina/transmisión , Tuberculosis/epidemiología , Tuberculosis/microbiología , Tuberculosis/transmisiónRESUMEN
With the hypothesis that genetic variability of Mycobacterium bovis could influence virulence and immunopathology, five M. bovis strains were selected from an epidemiological study in Argentina on the basis of their prevalence in cattle and occurrence in other species. We then determined the virulence and the immunopathology evoked by these strains in a well-characterized mouse model of progressive pulmonary tuberculosis. The reference strain AN5 was used as a control. BALB/c mice infected with this M. bovis reference strain showed 50% survival after 4 months of infection, with moderate bacillary counts in the lung. Two weeks after inoculation, it induced a strong inflammatory response with numerous granulomas and progressive pneumonia. In contrast, strain 04-303, isolated from a wild boar, was the most lethal and its most striking feature was sudden pneumonia with extensive necrosis. Strain 04-302, also isolated from wild boar but with a different spoligotype, induced similar pathology but to a lesser extent. In contrast, strains 534, V2 (both from cattle) and 02-2B (from human) were less virulent, permitting higher survival after 4 months of infection and limited tissue damage. Strain AN5 and the cattle and human isolates induced rapid, high and stable expression of interferon (IFN)-gamma and inducible nitric oxide synthase (iNOS). In contrast, the more virulent strains induced lower expression of IFN-gamma, tumour necrosis factor-alpha and iNOS. Interestingly, these more virulent strains induced very low expression of murine beta defensin 4 (mBD-4); whereas, the control strain AN5 induced progressive expression of this anti-microbial peptide, peaking at day 120. The less virulent strains induced high mBD-4 expression during early infection. Thus, as reported with clinical isolates of M. tuberculosis, M. bovis also showed variable virulence. This variability can be attributed to the induction of a different pattern of immune response.
Asunto(s)
Mycobacterium bovis/genética , Mycobacterium bovis/inmunología , Tuberculosis Pulmonar/inmunología , Animales , Bovinos , Enfermedades de los Bovinos/inmunología , Enfermedades de los Bovinos/microbiología , Ensayo de Unidades Formadoras de Colonias , Progresión de la Enfermedad , Variación Genética , Granuloma/microbiología , Interferón gamma/genética , Pulmón/inmunología , Pulmón/microbiología , Pulmón/patología , Ratones , Ratones Endogámicos BALB C , Modelos Animales , Óxido Nítrico Sintasa de Tipo II/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Enfermedades de los Porcinos/inmunología , Enfermedades de los Porcinos/microbiología , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/patología , Factor de Necrosis Tumoral alfa/genética , Virulencia , beta-Defensinas/genéticaRESUMEN
In the present work, 19 Mycobacterium bovis isolates from different cats were typified by spoligotyping. We detected nine spoligotypes. There was only one cluster, which grouped 11 of the isolates (57.9%), showing the main spoligotype from cattle from Argentina. The rest of the spoligotypes presented only one isolate each. Five of them were not found in cattle, and were unique and exclusive of cats. The isolates studied show that tuberculosis of bovine origin in cats constitutes a potential public health problem in Buenos Aires region. The identification of genotypes from non-natural hosts could contribute to understand the spread of bovine tuberculosis. This is the first report showing genetic profiles of M. bovis isolates in felines from Argentina.
Asunto(s)
Técnicas de Tipificación Bacteriana/métodos , Enfermedades de los Gatos/microbiología , Gatos/microbiología , ADN Bacteriano/análisis , Mycobacterium bovis/aislamiento & purificación , Reacción en Cadena de la Polimerasa/métodos , Tuberculosis/veterinaria , Alimentación Animal/efectos adversos , Alimentación Animal/microbiología , Animales , Argentina/epidemiología , Enfermedades de los Gatos/epidemiología , Enfermedades de los Gatos/transmisión , Bovinos , ADN Bacteriano/genética , Reservorios de Enfermedades/microbiología , Reservorios de Enfermedades/veterinaria , Contaminación de Alimentos , Microbiología de Alimentos , Pulmón/microbiología , Mycobacterium bovis/clasificación , Mycobacterium bovis/genética , Tuberculosis/epidemiología , Tuberculosis/microbiología , Tuberculosis/transmisión , Tuberculosis Bovina/epidemiología , Tuberculosis Bovina/microbiología , Tuberculosis Bovina/transmisiónRESUMEN
The authors present the results of a study conducted using time series data from the 1993--2001 period in order to characterise the clinical behaviour of bovine paratuberculosis. The case data, confirmed by macroscopic examination, enzyme-linked immunosorbent assay (ELISA) and comparative tuberculin test, came from the herd health register, located in Tandil in the province of Buenos Aires, Argentina. The upper limit of customary variation was observed in April, with an incidence of 2.5%. In 1997, 1999, 2000 and 2001 the disease was epidemic and a peak of 5.6% occurred in March 1999. Over the long term a rise in the total annual incidence was observed, from 0.7% in 1993 to 10.2% in 2001. Knowledge about the epidemiology of paratuberculosis will help to control the disease and minimise its impact on the national economy, and will also provide new information for use in public health.
Asunto(s)
Enfermedades de los Bovinos/epidemiología , Paratuberculosis/epidemiología , Salud Pública , Animales , Argentina/epidemiología , Bovinos , Enfermedades de los Bovinos/prevención & control , Enfermedades de los Bovinos/transmisión , Ensayo de Inmunoadsorción Enzimática/veterinaria , Humanos , Incidencia , Paratuberculosis/prevención & control , Paratuberculosis/transmisión , Prueba de Tuberculina/veterinariaRESUMEN
The authors present the results of a comparative intradermal tuberculin test performed on dairy sheep to determine rates of reaction to bovine and avian purified protein derivative (PPD). Test reactions were interpreted by palpation and measurement with a calliper. Results were analysed by plotting the values obtained. Agar gel immunodiffusion tests, growth in culture and histopathological examinations were also performed to allow differential diagnosis between tuberculosis and paratuberculosis. In the first tuberculin test, performed on 288 sheep, 74 animals showed a positive reaction to avian PPD (25.69%), two animals showed a positive reaction to bovine PPD (0.69%), and one animal was positive with respect to both tuberculins (0.34%). In the second test, involving 247 sheep, 55 demonstrated a positive reaction to avian PPD (22.26%), whilst none reacted to bovine PPD. The presence of Mycobacterium avium subsp. paratuberculosis was confirmed by culture and serological testing. In addition, lesions compatible with those caused by M. bovis were found by histopathological examination. These findings highlight the importance of the accurate diagnosis of tuberculosis and paratuberculosis for the effective control of both diseases.
Asunto(s)
Paratuberculosis/diagnóstico , Enfermedades de las Ovejas/diagnóstico , Tuberculosis/veterinaria , Animales , Anticuerpos Antibacterianos/sangre , Diagnóstico Diferencial , Femenino , Inmunodifusión/veterinaria , Pruebas Intradérmicas/veterinaria , Mycobacterium avium subsp. paratuberculosis/inmunología , Mycobacterium bovis/inmunología , Paratuberculosis/complicaciones , Ovinos , Prueba de Tuberculina/veterinaria , Tuberculosis/complicaciones , Tuberculosis/diagnósticoRESUMEN
The first case of tuberculosis is described in a wild subantarctic fur seal (Arctocephalus tropicalis) found on the Argentine coast. There was hydrothorax and white firm granulomatous lesions of 40-50 mm in diameter in the lungs. Lesions consisted of a central area of caseous necrosis, an intermediate zone of epithelioid and lymphocytic mononuclear cells, and a peripheral zone of connective tissue. Biochemical and drug sensitivity tests and inoculation of Guinea pigs confirmed the identification as Mycobacterium tuberculosis complex. Arctocephalus tropicalis is the fifth pinniped species in which the M. tuberculosis complex has been detected. Since subantarctic fur seals are widely distributed in the Southern Hemisphere, it is possible that the tuberculosis cases may have a common origin and could spread to other austral regions and species.
Asunto(s)
Lobos Marinos , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis Pulmonar/veterinaria , Animales , Regiones Antárticas , Argentina , Resultado Fatal , Cobayas , Pulmón/patología , Ganglios Linfáticos/patología , Masculino , Prueba de Tuberculina/veterinaria , Tuberculosis Pulmonar/diagnósticoRESUMEN
Diverse pathological conditions causing the strandings and/or deaths of several species of sea lions and seals on the northern coast of the province of Buenos Aires are being studied. Tuberculosis was diagnosed in six cases of strandings, involving two otariid seal species (one Otaria flavescens and five Arctocephalus australis), between March 1989 and December 1992. Necropsies were performed on all six cases. Granulomatous lesions were observed in the prescapular and hepatic lymph nodes. Lesions were also seen in the lungs, pleura, liver, spleen and peritoneum. Bacteriological isolation was attempted from all the samples. The isolates were identified as belonging to the Mycobacterium tuberculosis complex. Some showed characteristics consistent with M. bovis, whereas others demonstrated properties of M. tuberculosis. Genomic deoxyribonucleic acid (DNA) from these strains was analysed by restriction fragment length polymorphism (RFLP), using IS6110, a genetic marker found only in the Mycobacterium tuberculosis complex. Using the IS6110 probe, similar fingerprints were obtained, suggesting a common source of infection. However, the pattern of DNA differed from DNA patterns of M. bovis isolated from humans and cattle in Argentina, which generally contain a unique 1.9 kbp band. These results suggest that mycobacteria isolated from wild seals form a different grouping inside the M. tuberculosis complex. This is the first time that tuberculosis has been detected in wild seals from the south-western Atlantic coast.
Asunto(s)
Lobos Marinos , Leones Marinos , Tuberculosis/veterinaria , Animales , Argentina/epidemiología , Océano Atlántico , ADN Bacteriano/análisis , ADN Bacteriano/química , Femenino , Hígado/patología , Pulmón/patología , Ganglios Linfáticos/patología , Masculino , Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Polimorfismo de Longitud del Fragmento de Restricción , Tuberculosis/epidemiología , Tuberculosis/patologíaRESUMEN
Different diagnostic techniques for mycobacteria were studied in sea lions, sea elephants, fur seals, dolphins, killer whales and penguins from a sea aquarium. Three strains were isolated from fur seals. Two were classified as Mycobacterium chelonae and one as Mycobacterium fortuitum complex. There was good correlation between the results given by the intradermal tuberculin test and ELISA, but the former is recommended as a screening test on the basis of its practicality. Results and methodology of the different techniques are described.
Asunto(s)
Enfermedades de las Aves/diagnóstico , Delfines , Infecciones por Mycobacterium no Tuberculosas/veterinaria , Phocidae , Ballenas , Animales , Anticuerpos Antibacterianos/sangre , Aves , Ensayo de Inmunoadsorción Enzimática , Mycobacterium/inmunología , Mycobacterium/aislamiento & purificación , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Mycobacterium chelonae/inmunología , Mycobacterium chelonae/aislamiento & purificación , Valor Predictivo de las Pruebas , Agua de Mar , Prueba de Tuberculina/veterinariaRESUMEN
El objeto de este proyecto fue obtener una provision de sensitinas micobacterianas puras y estandarizadas, que podrian emplearse en el futuro en la Republica Argentina en estudios experimentales o epidemiologicos. Se prepararan 17 lotes de sensitinas (derivados proteinicos purificados) a partir de 17 cepas de referencia de las siguientes especies o grupos micobacterianos: (a) Complejo M-avium-intracellulare-scrofulaceum (MAIS) serotipos 1, 4 6, 7, 10, 11, 15, 16, 17, 20, 41 y M avium cepa D4; (b) Especies de crecimiento rapido M. fortuitum y M. chelonei; (c) Especies fotocromogenas M. kansasii y M. marinum. La especificidad de estos preparados se determino por pruebas intradermicas comparativas hechas a grupos de cobayos previamente sensibilizados con las cepas originales. Seis de los 10 antigenos preparados del complejo MAIS, y las 3 sensitinas de M. fortuitum, M. chelonei y M.kansasii mostraron un grado aceptable de especificidad. Por lo tanto, estos preparados podrian resultar de utilidad en estudios sobre la sensibilizacion natural por esas especies de micobacterias en poblaciones humanas y en ganado bovino de la Republica Argentina
Asunto(s)
Animales , Mycobacterium tuberculosis , Pruebas de Sensibilidad Microbiana , CobayasRESUMEN
El objeto de este proyecto fue obtener una provision de sensitinas micobacterianas puras y estandarizadas, que podrian emplearse en el futuro en la Republica Argentina en estudios experimentales o epidemiologicos. Se prepararan 17 lotes de sensitinas (derivados proteinicos purificados) a partir de 17 cepas de referencia de las siguientes especies o grupos micobacterianos: (a) Complejo M-avium-intracellulare-scrofulaceum (MAIS) serotipos 1, 4 6, 7, 10, 11, 15, 16, 17, 20, 41 y M avium cepa D4; (b) Especies de crecimiento rapido M. fortuitum y M. chelonei; (c) Especies fotocromogenas M. kansasii y M. marinum. La especificidad de estos preparados se determino por pruebas intradermicas comparativas hechas a grupos de cobayos previamente sensibilizados con las cepas originales. Seis de los 10 antigenos preparados del complejo MAIS, y las 3 sensitinas de M. fortuitum, M. chelonei y M.kansasii mostraron un grado aceptable de especificidad. Por lo tanto, estos preparados podrian resultar de utilidad en estudios sobre la sensibilizacion natural por esas especies de micobacterias en poblaciones humanas y en ganado bovino de la Republica Argentina