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1.
Nat Mater ; 22(7): 867-872, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37349399

RESUMO

The emergence of a topological transition of the polaritonic dispersion in twisted bilayers of anisotropic van der Waals materials at a given twist angle-the photonic magic angle-results in the diffractionless propagation of polaritons with deep-subwavelength resolution. This type of propagation, generally referred to as canalization, holds promise for the control of light at the nanoscale. However, the existence of a single photonic magic angle hinders such control since the canalization direction in twisted bilayers is unique and fixed for each incident frequency. Here we overcome this limitation by demonstrating multiple spectrally robust photonic magic angles in reconfigurable twisted α-phase molybdenum trioxide (α-MoO3) trilayers. We show that canalization of polaritons can be programmed at will along any desired in-plane direction in a single device with broad spectral ranges. These findings open the door for nanophotonics applications where on-demand control is crucial, such as thermal management, nanoimaging or entanglement of quantum emitters.


Assuntos
Fótons , Anisotropia
2.
Phys Rev Lett ; 130(20): 201901, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37267571

RESUMO

The LHCb collaboration has recently reported the largest CP violation effect from a single amplitude, as well as other giant CP asymmetries in several B-meson decays into three charmless light mesons. It is also claimed that this is predominantly due to ππ→KK[over ¯] rescattering in the final state, particularly in the 1 to 1.5 GeV region. In these analyses the ππ→KK[over ¯] amplitude is by default estimated from the ππ elastic scattering amplitude and does not describe the existing ππ→KK[over ¯] scattering data. Here we show how the recent model-independent dispersive analysis of ππ→KK[over ¯] data can be easily implemented in the LHCb formalism. This leads to a more accurate description of the asymmetry, while being consistent with the measured scattering amplitude and confirming the prominent role of hadronic final state interactions, paving the way for more elaborated analyses.

3.
Rev. mex. ing. bioméd ; 41(1): 43-56, ene.-abr. 2020. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1139323

RESUMO

Abstract In this paper, we present a novel approach to training classifiers in a speller based on P300 potentials. The method, based on bootstrapping, is a known strategy for generating new samples, but it is rarely used in neurosciences. The study first demonstrates how the performance of the classification task (detecting P300 and Non-P300 classes) could be sub-optimal in the traditional approach. Then, a new method for taking new samples from the training data is proposed. Each classifier is re-trained using balanced sub-groups of individual P300 and non-P300 samples. Data were collected from 14 healthy subjects, using 16 electroencephalography channels. These were filtered in bandpass and decimated. Subsequently, four linear classifiers were trained using the traditional method followed by the proposed one, with 1000, 2000 and 3000 samples per class. Results indicate an improvement in the accuracy and discrimination capacity of discriminative classifiers with the proposed method, maintaining the same statistical properties between the training and test data. By contrast, for generative classifiers, there is no significant difference in the results. Therefore, the proposed method is highly recommended for training discriminative classifiers in spell-based P300 potentials.


Resumen Este artículo presenta un método novedoso para entrenar clasificadores en un deletreador basado en potenciales P300. El método, basado en bootstrapping, es una estrategia conocida para generar nuevas muestras pero escasamente implementado en neurociencias. El estudio muestra cómo el rendimiento de la detección de P300 (frente a No-P300) puede resultar sub-óptimo usando el método tradicional. Luego, se propone un nuevo método donde se toman nuevas muestras a partir de los datos de entrenamiento. Con ellas, se re-entrena al clasificador usando sub-grupos equilibrados de muestras individuales P300 y No-P300. Los datos se recolectaron de 14 sujetos sanos, usando 16 canales de electroencefalografía. Estos fueron filtrados en pasa-banda y diezmados. Posteriormente, cuatro clasificadores lineales fueron entrenados, usando primero el método tradicional y después el método propuesto, con 1000, 2000 y 3000 muestras por clase. Los resultados muestran una mejoría en la precisión y la capacidad de discriminación de clasificadores discriminativos con el método propuesto, manteniendo las mismas propiedades estadísticas entre los datos de entrenamiento y los de prueba. En contraste, para los clasificadores generativos, no existe una diferencia significativa en los resultados. Por consiguiente, el método propuesto es altamente recomendado para entrenar clasificadores discriminativos en deletreadores basados en potenciales P300.

4.
Cir Pediatr ; 28(1): 36-39, 2015 Jan 13.
Artigo em Espanhol | MEDLINE | ID: mdl-27775269

RESUMO

Intussusception in infants and young children is a relatively common entity with a well defined clinical picture and a favorable outcome in most cases.The neonatal intussusceptions is extremely rare and does not have a well-defined clinical picture since its clinical manifestations vary according to the gestational time it occurs, the response of the injured intestine and the gestational age of the child concerned. Two new cases of neonatal intussusceptions are presented and a review of the world literature is performed. Given the stage of intussusceptions (pre- or postnatal) occurs and gestational age of the affected infant (preterm or term), there are three entities with clinical characteristics, topography and evolution rather different: prenatal or intrauterine intussusception, postnatal intussusception in the preterm and postnatal intussusception in the term infant.


La invaginación intestinal en el lactante y niño pequeño es una entidad relativamente frecuente, con un cuadro clínico definido y una evolución favorable en la mayoría de los casos. La invaginación intestinal neonatal es sumamente rara y no tiene un cuadro bien definido, ya que sus manifestaciones clínicas varían de acuerdo con el momento gestacional en que se produce, con la respuesta del intestino lesionado y con la edad gestacional del niño afectado. Se presentan dos nuevos casos de invaginación intestinal neonatal y se realiza una revisión de la bibliografía mundial. Teniendo en cuenta la etapa en que se produce la invaginación (pre o postnatal) y la edad gestacional del neonato afectado (prematuro o a término), se pueden distinguir tres entidades con características clínicas, topográficas y evolutivas bien diferentes: la invaginación intestinal prenatal o intraútero, la invaginación intestinal postnatal en el prematuro y la invaginación intestinal postnatal en el neonato a término.

5.
Actas Dermosifiliogr ; 105(5): 487-96, 2014 Jun.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-24630429

RESUMO

INTRODUCTION AND OBJECTIVES: To analyze the triggers of atopic dermatitis (AD), adherence to medical recommendations, disease control, and health-related quality of life (HRQOL) from the patient's perspective. PATIENTS AND METHODS: This was a multicenter, cross-sectional, epidemiological study with the participation of adults (age >16 years; n=125) and children (age, 2-15 years, n=116). Patients had a history of at least 12 months of moderate to severe AD with a moderate to severe flare (Investigator Global Assessment score>2) at the time of recruitment. The Mann-Whitney U test was used to evaluate relationships between disease severity, determined according to the Scoring in Atopic Dermatitis index, and triggers reported by patients, adherence to recommendations and pharmacological therapy, HRQOL, and patient-perceived control. RESULTS: The most common triggers were cosmetic products, clothing, mites, detergents/soaps, and changes in temperature. In 47.2% of adults and 39.7% of children, pharmacological therapy was not initiated at flare onset. Adherence was highest to pharmacological therapy, skin moisturizing, and medical care recommendations. Disease control was considered insufficient by 41.6% of adults and 27. 6% of pediatric patients and, in adults, this was associated with the severity of AD (P=.014). CONCLUSIONS: The therapeutic control of AD is susceptible to improvement, especially in adults. Although patients state that they follow medical recommendations, a significant percentage of patients do not apply recommended treatments correctly. Better education about the disease and its management would appear to be necessary to improve disease control and HRQOL.


Assuntos
Dermatite Atópica/etiologia , Dermatite Atópica/terapia , Cooperação do Paciente , Qualidade de Vida , Adolescente , Adulto , Atitude Frente a Saúde , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Adulto Jovem
7.
Actas Dermosifiliogr ; 104(5): 409-17, 2013 Jun.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-23665434

RESUMO

OBJECTIVE: To evaluate health-related quality of life (HRQOL), patient satisfaction, and adherence to treatment in patients with moderate or severe atopic dermatitis on maintenance therapy. MATERIAL AND METHODS: We performed a national, multicenter, cross-sectional, epidemiological study in adults and children with moderate or severe atopic dermatitis of at least 16 months' duration who were receiving maintenance therapy. We used the Dermatology Life Quality Index (DLQI), the children's version of this scale (cDLQI), and the Morisky medication adherence scale. Visual analog scales were used to measure treatment satisfaction. We used the Mann-Whitney U test to compare HRQOL between patients with moderate and severe disease and the Wilcoxon test to compare the frequency and duration of flares before and after the start of maintenance therapy. RESULTS: We studied 141 children and 141 adults; the prevalence of moderate AD in these groups was 85.8% and 79.4%, respectively. The impact of AD on HRQOL was mild to moderate. Maintenance therapy led to a significant decrease in the frequency and duration of flares (P < .001). While treatment satisfaction was high in both groups, adherence was poor (18.4%-42.6% in children and 14.9%-27.0% in adults). CONCLUSIONS: Patients with moderate and severe AD receiving maintenance therapy experience a reduction in the number and duration of flares and an improvement in HRQOL. While treatment satisfaction is high, adherence rates could be improved.


Assuntos
Dermatite Atópica/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Satisfação do Paciente , Qualidade de Vida , Adulto , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Índice de Gravidade de Doença
8.
Oecologia ; 173(1): 83-93, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23386048

RESUMO

Animals often announce their unprofitability to predators through conspicuous coloured signals. Here we tested whether the apparently conspicuous colour designs of the four European Coraciiformes and Upupiformes species may have evolved as aposematic signals, or whether instead they imply a cost in terms of predation risk. Because previous studies suggested that these species are unpalatable, we hypothesized that predators could avoid targeting them based on their colours. An experiment was performed where two artificial models of each bird species were exposed simultaneously to raptor predators, one painted so as to resemble the real colour design of these birds, and the other one painted using cryptic colours. Additionally, we used field data on the black kite's diet to compare the selection of these four species to that of other avian prey. Conspicuous models were attacked in equal or higher proportions than their cryptic counterparts, and the attack rate on the four species increased with their respective degree of contrast against natural backgrounds. The analysis of the predator's diet revealed that the two least attacked species were negatively selected in nature despite their abundance. Both conspicuous and cryptic models of one of the studied species (the hoopoe) received fewer attacks than cryptic models of the other three species, suggesting that predators may avoid this species for characteristics other than colour. Globally, our results suggest that the colour of coraciiforms and upupiforms does not function as an aposematic signal that advises predators of their unprofitability, but also that conspicuous colours may increase predation risk in some species, supporting thus the handicap hypothesis.


Assuntos
Comunicação Animal , Aves/anatomia & histologia , Cor , Comportamento Predatório , Aves Predatórias/fisiologia , Animais , Sinais (Psicologia) , Dieta , Fatores de Risco
9.
Eur J Cancer Care (Engl) ; 22(3): 400-12, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23331323

RESUMO

We conducted a multicentre, retrospective, observational study including patients with solid tumours (excluding breast cancer) that received granulocyte colony-stimulating factors (G-CSF) and chemotherapy. We investigated the effectiveness of daily vs. non-daily G-CSFs (pegfilgrastim) adjusting by potential confounders. The study included 391 patients (211 daily G-CSF; 180 pegfilgrastim), from whom 47.3% received primary prophylaxis (PP) (57.8% pegfilgrastim), 26.3% secondary prophylaxis (SP: initiation after cycle 1 and no reactive treatment in any cycle) (51.5% pegfilgrastim) and 26.3% reactive treatment (19.4% pegfilgrastim). Only 42.2% of patients with daily G-CSF and 46.2% with pegfilgrastim initiated prophylaxis within 72 h after chemotherapy, and only 10.5% of patients with daily G-CSF received it for ≥ 7 days. In the multivariate models, daily G-CSF was associated with higher risk of grade 3-4 neutropenia (G3-4N) vs. pegfilgrastim [odds ratio (OR): 1.73, 95% confidence interval (CI): 1.004-2.97]. Relative to SP, PP protected against G3-4N (OR for SP vs. PP: 6.0, 95%CI: 3.2-11.4) and febrile neutropenia (OR: 3.1, 95%CI: 1.1-8.8), and was associated to less chemotherapy dose delays and reductions (OR for relative dose intensity <85% for SP vs. PP: 3.1, 95%CI: 1.7-5.4) and higher response rate (OR: 2.1, 95%CI: 1.2-3.7). Data suggest that pegfilgrastim, compared with a daily G-CSF, and PP, compared with SP, could be more effective in preventing neutropenia and its related events in the clinical practice.


Assuntos
Antineoplásicos/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neoplasias/tratamento farmacológico , Neutropenia/prevenção & controle , Idoso , Quimioterapia Combinada , Feminino , Filgrastim , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/complicações , Polietilenoglicóis , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos
10.
Rev Esp Quimioter ; 24(3): 154-63, 2011 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-21947099

RESUMO

OBJECTIVE: To assess the efficiency of daptomycin as firstline therapy (D) versus daptomycin as salvage therapy after vancomycin (V→D ) or linezolid (L→D) failure in gram-positive bacteraemia and complicated skin and skin-structure infections (cSSTIs). METHODS: Cost-effectiveness analysis of 161 bacteraemia and 84 cSSTIs patients comparing the above mentioned therapeutic alternatives was performed using the data from 27 Spanish hospitals involved in the EUCORE study. Direct medical costs were considered. Patients were observed from the first antibiotic dose for infection until either the end of daptomycin therapy or exitus. A multivariate Monte Carlo probabilistic sensitivity analysis was applied for costs (lognormal distribution) and effectiveness (normal distribution). RESULTS: In terms of effectiveness there were no statistical differences between groups but referring total costs per patient, there were significant differences. Sensitivity analysis confirmed that D dominates over L→D between 44.2%-62.1% of simulations in bacteraemia and between 48.2%-67.5% in cSSTIs. In comparison to V→D, D dominance was detected in 29.2%-33.2% of simulations in bacteraemia and between 48.2%-59.3% in cSSTIs. CONCLUSIONS: Daptomycin as first-line therapy dominates over daptomycin as salvage therapy after linezolid failure both in bacteraemia and cSSTIs. Comparing daptomycin as first-line therapy with its use after vancomycin failure, in cSSTIs the former is dominant. In bacteremia daptomycin as first line therapy is as effective as daptomycin as salvage therapy after vancomycin failure and implies lower costs.


Assuntos
Antibacterianos/economia , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Daptomicina/economia , Daptomicina/uso terapêutico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Dermatopatias Infecciosas/tratamento farmacológico , Acetamidas/economia , Acetamidas/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/economia , Bacteriemia/microbiologia , Análise Custo-Benefício , Interpretação Estatística de Dados , Bactérias Gram-Positivas/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/economia , Infecções por Bactérias Gram-Positivas/microbiologia , Hospitais , Humanos , Linezolida , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Método de Monte Carlo , Oxazolidinonas/economia , Oxazolidinonas/uso terapêutico , Terapia de Salvação , Dermatopatias Infecciosas/economia , Dermatopatias Infecciosas/microbiologia , Espanha , Falha de Tratamento , Vancomicina/economia , Vancomicina/uso terapêutico , Adulto Jovem
11.
Curr Med Chem ; 18(17): 2601-11, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21568889

RESUMO

The binding of various molecules to integral membrane proteins with optimal affinity and specificity is central to normal function of cell. While membrane proteins represent about one third of the whole cell proteome, they are a majority of common drug targets. The quest for the development of computational models capable of accurate evaluation of binding affinities, decomposition of the binding into its principal components and thus mapping molecular mechanisms of binding remains one of the main goals of modern computational biophysics and related drug development. The primary scope of this review will be on the recent extension of computational methods for the study of drug binding to membrane proteins. Several examples of such applications will be provided ranging from secondary transporters to voltage gated channels. In this mini-review, we will provide a short summary on the breadth of different methods for binding affinity evaluation. These methods include molecular docking with docking scoring functions, molecular dynamics (MD) simulations combined with post-processing analysis using Molecular Mechanics/Poisson Boltzmann (Generalized Born) Surface Area (MM/PB(GB)SA), as well as direct evaluation of free energies from Free Energy Perturbation (FEP) with constraining schemes, and Potential of Mean Force (PMF) computations. We will compare advantages and shortcomings of popular techniques and provide discussion on the integrative strategies for drug development aimed at targeting membrane proteins.


Assuntos
Entropia , Proteínas de Membrana/metabolismo , Ligação Proteica , Canalopatias/fisiopatologia , Desenho de Fármacos , Canal de Potássio ERG1 , Canais de Potássio Éter-A-Go-Go/efeitos dos fármacos , Fulerenos/metabolismo , Protease de HIV/metabolismo , Canais Iônicos/fisiologia , Ligantes , Proteínas de Membrana/efeitos dos fármacos , Modelos Moleculares , Simulação de Dinâmica Molecular , Fenetilaminas/farmacologia , Sulfonamidas/farmacologia
12.
ACS Med Chem Lett ; 2(10): 786-91, 2011 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-24900267

RESUMO

We have investigated a novel series of acid-derived γ-secretase modulators as a potential treatment of Alzheimer's disease. Optimization based on cellular potency and brain pharmacodynamics after oral dosing led to the discovery of 10a (BIIB042). Compound 10a is a potent γ-secretase modulator, which lowered Aß42, increased Aß38, but had little to no effect on Aß40 levels both in vitro and in vivo. In addition, compound 10a did not affect Notch signaling in our in vitro assessment. Compound 10a demonstrated excellent pharmacokinetic parameters in multiple species. Oral administration of 10a significantly reduced brain Aß42 levels in CF-1 mice and Fischer rats, as well as plasma Aß42 levels in cynomolgus monkeys. Compound 10a was selected as a candidate for preclinical safety evaluation.

13.
Cir Pediatr ; 20(1): 63-7, 2007 Jan.
Artigo em Espanhol | MEDLINE | ID: mdl-17489498

RESUMO

The splenic cysts are rare among all age groups and there are a few reports in the world literature. The splenic epidermoid cyst is a true congenital one, that can cause signs and symptoms, or suffer complications. For these reasons, some form of treatment is recommended. The management of splenic cysts continues to evolve. The standard treatment was splenectomy, but the knowledge about the immunologic function of the spleen and the existence of postesplenectomy mortal sepsis, have conduced most of pediatric surgeons to adopt techniques that preserves splenic tissue. The treatment by percutaneous drainage with injection of a sclerosing agent has complications and a significant recurrence rate. During the last two decades, preservation procedures such as partial splenectomy or partial cyst excision and omental packing have gained the preference of most pediatric surgeons. The second technique has advantages over the partial splenectomy. The possibility to perform the procedure by a laparoscopic approach add the advantages of this last technique. We present two patients with splenic epidermoid cyst treated by laparoscopic partial cyst decapsulation and review the literature.


Assuntos
Cisto Epidérmico/cirurgia , Laparoscopia/métodos , Esplenopatias/cirurgia , Adolescente , Criança , Cisto Epidérmico/diagnóstico por imagem , Feminino , Humanos , Radiografia , Esplenopatias/diagnóstico por imagem
14.
Evolution ; 60(4): 856-68, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16739465

RESUMO

Patterns of selection are widely believed to differ geographically, causing adaptation to local environmental conditions. However, few studies have investigated patterns of phenotypic selection across large spatial scales. We quantified the intensity of selection on morphology in a monogamous passerine bird, the barn swallow Hirundo rustica, using 6495 adults from 22 populations distributed across Europe and North Africa. According to the classical Darwin-Fisher mechanism of sexual selection in monogamous species, two important components of fitness due to sexual selection are the advantages that the most attractive males acquire by starting to breed early and their high annual fecundity. We estimated directional selection differentials on tail length (a secondary sexual character) and directional selection gradients after controlling for correlated selection on wing length and tarsus length with respect to these two fitness components. Phenotype and fitness components differed significantly among populations for which estimates were available for more than a single year. Likewise, selection differentials and selection gradients differed significantly among populations for tail length, but not for the other two characters. Sexual selection differentials differed significantly from zero across populations for tail length, particularly in males. Controlling statistically for the effects of age reduced the intensity of selection by 60 to 81%, although corrected and uncorrected estimates were strongly positively correlated. Selection differentials and gradients for tail length were positively correlated between the sexes among populations for selection acting on breeding date, but not for fecundity selection. The intensity of selection with respect to breeding date and fecundity were significantly correlated for tail length across populations. Sexual size dimorphism in tail length was significantly correlated with selection differentials with respect to breeding date for tail length in male barn swallows across populations. These findings suggest that patterns of sexual selection are consistent across large geographical scales, but also that they vary among populations. In addition, geographical patterns of phenotypic selection predict current patterns of phenotypic variation among populations, suggesting that consistent patterns of selection have been present for considerable amounts of time.


Assuntos
Passeriformes/genética , Passeriformes/fisiologia , Fatores Etários , Migração Animal , Animais , Meio Ambiente , Europa (Continente) , Evolução Molecular , Feminino , Geografia , Masculino , Fenótipo , Caracteres Sexuais , Comportamento Sexual Animal
16.
BMC Evol Biol ; 3: 6, 2003 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-12702218

RESUMO

BACKGROUND: An important component of sexual selection arises because females obtain viability benefits for their offspring from their mate choice. Females choosing extra-pair fertilization generally favor males with exaggerated secondary sexual characters, and extra-pair paternity increases the variance in male reproductive success. Furthermore, females are assumed to benefit from 'good genes' from extra-pair sires. How additive genetic variance in such viability genes is maintained despite strong directional selection remains an evolutionary enigma. We propose that sexual selection is associated with elevated mutation rates, changing the balance between mutation and selection, thereby increasing variance in fitness and hence the benefits to be obtained from good genes sexual selection. Two hypotheses may account for such elevated mutation: (1) Increased sperm production associated with sperm competition may increase mutation rate. (2) Mutator alleles increase mutation rates that are revealed by the expression of condition-dependent secondary sexual characters used by choosy females during their mate choice. M Petrie has independently developed the idea that mutator alleles may account for the maintenance of genetic variation in viability despite strong directional selection. RESULTS: A comparative study of birds revealed a positive correlation between mutation rate at minisatellite loci and extra-pair paternity, but not between mutation rate and relative testes mass which is a measure of relative sperm production. Minisatellite mutation rates were not related to longevity, suggesting a meiotic rather than a mitotic origin of mutations. CONCLUSION: We found evidence of increased mutation rate in species with more intense sexual selection. Increased mutation was not associated with increased sperm production, and we suggest that species with intense sexual selection may maintain elevated mutation rates because sexual selection continuously benefits viability alleles expressed in condition-dependent characters. Sexual selection may increase mutational input, which in turn feeds back on sexual selection because of increased variance in viability traits.


Assuntos
Mutação em Linhagem Germinativa , Mutagênese , Seleção Genética , Comportamento Sexual Animal/fisiologia , Espermatozoides/fisiologia , Animais , Evolução Molecular , Masculino , Modelos Biológicos , Modelos Genéticos , Caramujos/genética , Espermatozoides/metabolismo
17.
Rev. cir. infant ; 11(1): ERRO-03_19-5, mar. 2001. tab
Artigo em Espanhol | LILACS | ID: lil-354095

RESUMO

El objetivo del trabajo es analizar en forma retrospectiva en una serie consecutiva de niños con malformación anorrectal(MAR)los aspectos clínicos,la táctica y resultados funcionales obtenidos.Entre junio de 1989 y Junio de 1999 fueron evaluados y tratados quirúrgicamente en forma primaria 115 pacientes con MAR(55 mujeres y 60 varones)Tipos de defecto;41 malformaciones bajas,30 fistulas vestibulares,11 sin fistula,10 fístulas recto-vesicales,8 fístulas recto-bulbares,2 atresias rectales,1 estenosis rectal,1 cloaca y 2 malformaciones asociadas.Hubo buena correlación entre el desarrollo perineal y lesiones de sacro.Se realizaron 80 colostomías(68 sigmoideas,10 transversas derechas,2 transversas izquierdas)Once pacientes fueron reoperados para modificar el tipo de ostomia previa al descenso,3 presentaron complicaciones inherentes a su ostomía que obligaron a cirugía y 3 fueron colostomizados sin que fuera necesario por el tipo de malformación anorrectal.Todos los pacientes fueron corregidos mediante anorrectoplastia sagital posterio.Presentaron complicaciomes 16 pacientes que requirieron algún tipo de solución quirúrgica.Doce pacientes presentaron complicaciones en el cierre de la colostomía.Los pacientes fueron divididos en 3 grupos(sin alteracion sacra,con alteración sacra mínima y con alteración sacra severa.En el primer grupo(85 pacientes)77 presentaron defecación voluntaria(90.58 por ciento)en el segundo grupo(5 pacientes)3 presentan defecación voluntaria y en el tercer grupo(8 pacientes)solo 3 presentan defecación voluntaria.Sobre 98 pacientes evaluados,83 presentan defecación voluntaria y 15 son incontinentes


Assuntos
Pré-Escolar , Criança , Canal Anal , Cirurgia Geral , Colostomia , Anormalidades Congênitas , Reto , Pediatria
18.
J Immunol Methods ; 227(1-2): 121-35, 1999 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-10485260

RESUMO

Upon treatment with protein therapeutics, a subset of patients will typically develop antibodies against the drug. These anti-drug antibodies can be of concern because they have the potential to alter the drug's therapeutic activity. In the case of relapsing-remitting multiple sclerosis (RRMS) patients receiving recombinant interferon-beta (IFN-beta), those receiving BETASERON (IFN-beta-1b; E. coli expressed, non-glycosylated, des-Met-1, Cys17Ser recombinant IFN-beta) have a higher incidence of IFN-beta specific antibodies compared to those receiving AVONEX (IFN-beta-1a; mammalian cell-expressed, natural sequence, glycosylated recombinant IFN-beta). The current study reports the development and characterization of ELISAs that detect distinct components of the anti-IFN-beta response in patients' sera, and therefore can potentially be used to characterize the composition of the anti-IFN-beta antibody response. ELISAs were developed using a constant detecting reagent but a variety of IFN-beta-derived test antigens (e.g., native IFN-beta, biotinylated IFN-beta, IFN-beta peptides) and capture methods. Assays were characterized using serum samples from a small number of patients treated with recombinant IFN-beta (either BETASERON or AVONEX). Assays in which IFN-beta was captured via a specific mAb, or in which biotinylated IFN-beta was captured via streptavidin, detected serum antibodies that recognize IFN-beta in its native structural state. In contrast, assays in which IFN-beta was coated directly onto the assay plates detected antibodies that recognize forms of IFN-beta possessing a folded structure distinct from the native structure. Certain epitopes present on native IFN-beta were not represented in these assays in which the test antigen was directly coated on plastic. Antibodies specific for linear epitopes could be detected using linear peptides as test antigens; the locations of these epitopes were mapped by reference to the X-ray crystal structure of IFN-beta-1a. Together, these data show that the mode of antigen presentation employed in IFN-beta ELISAs determines which antibody specificities are detected, and can affect whether or not a given serum sample is identified as positive for anti-IFN-beta antibodies. As a consequence, screening samples in a single ELISA format presenting IFN-beta in a non-native form may lead to underestimation of the incidence of IFN-beta treated MS patients that have generated antibodies specific to the native, active form of the drug.


Assuntos
Anticorpos/sangue , Interferon beta/imunologia , Esclerose Múltipla/terapia , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Epitopos , Humanos , Interferon beta-1a , Interferon beta-1b , Interferon beta/uso terapêutico , Esclerose Múltipla/imunologia , Proteínas Recombinantes/imunologia
19.
Biochemistry ; 37(24): 8743-53, 1998 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-9628736

RESUMO

We have used chemical cross-linking to identify sequences in integrin alpha4beta1 that are involved in its interactions with ligands. A recently described leucine-aspartic acid-valine (LDV)-based small molecule inhibitor of alpha4beta1 (BIO-1494), that contained a single reactive amino group for targeting the cross-linking, was used for these studies. The specificity of the interaction was defined by (i) the ability to block the interaction with a competitive inhibitor lacking the reactive group, (ii) the absolute requirement of divalent cations for cross-linking, and (iii) the lack of cross-linking to the functionally related integrin alpha4beta7. With ANB-NOS as the cross-linker, only the beta1 chain was labeled with BIO-1494, while with the more flexible cross-linker DSS both the alpha4 and beta1 chains were modified. Similar results were obtained when cross-linking was performed on K562 cells expressing alpha4beta1 but not on K562 cells expressing alpha2beta1. The site of cross-linking on the beta1 chain was localized by CNBr peptide mapping within residues 130-146, a region that contains the putative metal binding site DXSXS and for which analogous data had been generated with RGD binding to integrin alphaIIbbeta3. The striking similarity between the data we generated for an LDV ligand and published data for the RGD family supports the notion of a common ligand binding pocket formed by both integrin chains. The cross-linking strategy developed here should serve as a useful tool for studying alpha4beta1 function.


Assuntos
Integrinas/química , Receptores de Retorno de Linfócitos/química , Sequência de Aminoácidos , Sítios de Ligação/genética , Linhagem Celular , Reagentes de Ligações Cruzadas , Humanos , Integrina alfa4beta1 , Integrinas/genética , Integrinas/metabolismo , Ligantes , Dados de Sequência Molecular , Mapeamento de Peptídeos , Receptores de Retorno de Linfócitos/genética , Receptores de Retorno de Linfócitos/metabolismo
20.
Rev Esp Cardiol ; 51(1): 27-34, 1998 Jan.
Artigo em Espanhol | MEDLINE | ID: mdl-9580165

RESUMO

BACKGROUND: Although many variables are useful predictors of post-infarction mortality, their predictive positive values are weak when applied individually. The aim of this study was to determine the prognostic value of the combination of left ventricular ejection fraction, ventricular late potentials and baroreflex sensitivity. PATIENTS AND METHODS: We studied 69 consecutive post-infarction patients. On the day of their discharge from the coronary unit, all patients underwent a two-dimensional echocardiography, to determine the ejection fraction as well as a high resolution electrocardiogram to detect late potentials. To a subset of 49 patients was carried out to learn their baroreflex sensitivity. The patients were followed for 14 +/- 7 months and the following cardiac end points were considered: sudden cardiac death, non sudden cardiac death and non-fatal episodes of sustained ventricular tachycardia or ventricular fibrillation. RESULTS: There were 8 end points: 3 sudden cardiac deaths, 3 non sudden cardiac deaths and 2 successfully resuscitated sustained ventricular tachycardia episodes. The rate of fibrinolysis was 55%. An ejection fraction < 45%, the presence of late potentials and a baroreflex sensitivity < 3.0 msec/mmHg were univariate predictors with predictive positive values of 33%, 24% and 16%, respectively. When ejection fraction < 45%, late potentials and baroreflex sensitivity < 3.0 were combined, we found a significant increase in the positive predictive value (50%). CONCLUSION: The combined determination of ejection fraction, ventricular late potentials and baroreflex sensitivity allows us to identify subset postinfarction patients with a high rate of cardiac complications.


Assuntos
Barorreflexo/fisiologia , Ecocardiografia , Eletrocardiografia , Infarto do Miocárdio/diagnóstico , Volume Sistólico , Idoso , Interpretação Estatística de Dados , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/fisiopatologia , Valor Preditivo dos Testes , Fatores de Tempo
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