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1.
J Chem Phys ; 150(18): 184308, 2019 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-31091918

RESUMEN

We present molecular-frame measurements of the recombination dipole matrix element (RDME) in CO2, N2O, and carbonyl sulfide (OCS) molecules using high-harmonic spectroscopy. Both the amplitudes and phases of the RDMEs exhibit clear imprints of a two-center interference minimum, which moves in energy with the molecular alignment angle relative to the laser polarization. We find that whereas the angle dependence of this minimum is consistent with the molecular geometry in CO2 and N2O, it behaves very differently in OCS; in particular, the phase shift which accompanies the two-center minimum changes sign for different alignment angles. Our results suggest that two interfering structural features contribute to the OCS RDME, namely, (i) the geometrical two-center minimum and (ii) a Cooper-like, electronic-structure minimum associated with the sulfur end of the molecule. We compare our results to ab initio calculations using time-dependent density functional theory and present an empirical model that captures both the two-center and the Cooper-like interferences. We also show that the yield from unaligned samples of two-center molecules is, in general, reduced at high photon energies compared to aligned samples, due to the destructive interference between molecules with different alignments.

2.
Phys Rev Lett ; 121(14): 143902, 2018 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-30339417

RESUMEN

We investigate the harmonic generation induced by the interaction of a laser field with a solid target. The harmonic spectra is composed of the contribution of two processes interpreted as interband and intraband transitions. The interband process corresponds to the recombination from an upper band, populated during the laser interaction, to a lower band. The intraband process originates from nonlinear processes of the current in individual bands. In this Letter, we develop a theory based on Wannier states and reveal in depth the underlying physics of intraband dynamics. In particular, this approach highlights the determinant role of transitions between different lattice wells. Furthermore, our approach provides quantitative predictions concerning high-order harmonic energy cutoffs, harmonic yields, and emission times.

3.
Clin Otolaryngol ; 43(2): 483-488, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-28981208

RESUMEN

OBJECTIVES: The aim of this study was to demonstrate in a prospective multicentre study that Barbed Reposition Pharyngoplasty (BRP) procedure is safe and effective in management of obstructive sleep apnoea/hypopnea syndrome (OSAHS) patients. DESIGN: Prospective study. SETTING: Multicentre study. PARTICIPANTS: Patients suffering from obstructive sleep apnoea. MAIN OUTCOMES MEASURES: Values of postoperative apnoea-hypopnea index (AHI), oxygen desaturation index (ODI), epworth sleepiness scale (ESS). RESULTS: 111 Barbed Reposition Pharyngoplasty procedures standing alone or as a part of multilevel surgery for OSAHS, performed between January and September 2016, were analysed in 15 different centres. The average hospitalisation period was 2.5 ± 0.5 days. The mean patient age was 46.3 ± 10.5 years. The average body mass index at the time of the procedure was 27.9 ± 3.2, and the majority of the patients were men (83%). The mean preoperative and postoperative apnoea/hypopnea index was 33.4 ± 19.5 and 13.5 ± 10.3, respectively (P < .001). The mean preoperative and postoperative ESS score was 10.2 ± 4.5 and 6.1 ± 3.6, respectively (P < .001). The mean preoperative and postoperative ODI were 29.6 ± 20.7 and 12.7 ± 10.8, respectively (P < .001). CONCLUSIONS: Patients undergoing BRP standing alone or as part of a multilevel approach for the treatment of OSAHS have a reasonable expectation for success with minimal morbidity.


Asunto(s)
Faringe/cirugía , Apnea Obstructiva del Sueño/cirugía , Adulto , Índice de Masa Corporal , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento
4.
Phys Rev Lett ; 118(3): 033201, 2017 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-28157344

RESUMEN

We report on spectral intensity and group delay measurements of the highest-occupied molecular-orbital (HOMO) recombination dipole moment of N_{2} in the molecular-frame using high harmonic spectroscopy. We take advantage of the long-wavelength 1.3 µm driving laser to isolate the HOMO in the near threshold region, 19-67 eV. The precision of our group delay measurements reveals previously unseen angle-resolved spectral features associated with autoionizing resonances, and allows quantitative comparison with cutting-edge correlated 8-channel photoionization dipole moment calculations.

5.
Poult Sci ; 95(3): 560-9, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26628343

RESUMEN

The addition of methionine in the poultry feed industry is still facing the relative efficacy dilemma between DL-methionine (DLM) and hydroxy-methionine (HMTBA). The aim of this study was to compare the effect of dietary DLM and HMTBA on broiler performance at different levels of total sulfur amino acids (TSAA). The treatments consisted of a basal diet without methionine addition, and 4 increasing methionine doses for both sources resulting in TSAA/Lysine ratios from 0.62 to 0.73 in the starter phase and 0.59 to 0.82 in the grower phase. The comparison of product performance was performed by three-way ANOVA analysis and by methionine efficacy calculation as an alternative method of comparison. Growth results obtained during the starter phase with the different methionine supplementations did not show significant growth responses to TSAA levels, indicating a lower methionine requirement in the starter phase than currently assumed. However, a significant methionine dose effect was obtained for the period 10 to 28 day of age and for the entire growth period of 0 to 28 day of age. Excepting a significant gender effect, the statistical analysis did not allow for the discrimination of methionine sources, and no interaction between source and dose level was observed up to 28 days of age. A significant interaction between source and dose level was observed for methionine efficacy for the grower phase, and the total growth period showed better HMTBA efficacy at higher TSAA value. The exponential model fitted to each methionine source for body weight response depending on methionine intake or for feed conversion ratio (FCR) depending on methionine doses did not allow the methionine sources to be distinguished. Altogether, these results conclude that methionine sources lead to similar performances response when compared at TSAA values around the broiler requirement level. These results also showed that at TSAA values above requirement, HMTBA had a better methionine efficacy value than DLM, caused by the different properties of that molecule, whereas below the TSAA requirement levels, the opposite was observed in females.


Asunto(s)
Fenómenos Fisiológicos Nutricionales de los Animales , Pollos/metabolismo , Dieta/veterinaria , Suplementos Dietéticos , Metionina/análogos & derivados , Metionina/metabolismo , Alimentación Animal/análisis , Animales , Pollos/crecimiento & desarrollo , Femenino , Masculino , Metionina/administración & dosificación
6.
Dermatol Online J ; 21(4)2015 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-25933079

RESUMEN

We report an 89-year-old man who presented with a slowly growing pigmented pedunculated tumor. The nodule was diagnosed as a spindle cell pedunculated malignant melanoma (PMM), a rare variant of spindle-cell malignant melanoma. The clinical presentation of this tumor and its histological and immunohistological features are discussed.


Asunto(s)
Neoplasias Faciales/patología , Melanoma/patología , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Neoplasias Faciales/metabolismo , Neoplasias Faciales/cirugía , Humanos , Inmunohistoquímica , Antígeno MART-1/metabolismo , Masculino , Melanoma/metabolismo , Melanoma/cirugía , Antígenos Específicos del Melanoma/metabolismo , Antígeno gp100 del Melanoma
7.
Phys Rev Lett ; 112(15): 153001, 2014 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-24785035

RESUMEN

High harmonic generation (HHG) is used to measure the spectral phase of the recombination dipole matrix element (RDM) in argon over a broad frequency range that includes the 3p Cooper minimum (CM). The measured RDM phase agrees well with predictions based on the scattering phases and amplitudes of the interfering s- and d-channel contributions to the complementary photoionization process. The reconstructed attosecond bursts that underlie the HHG process show that the derivative of the RDM spectral phase, the group delay, does not have a straightforward interpretation as an emission time, in contrast to the usual attochirp group delay. Instead, the rapid RDM phase variation caused by the CM reshapes the attosecond bursts.

8.
Phys Rev Lett ; 110(1): 013001, 2013 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-23383786

RESUMEN

A calculation of the second-order (rescattering) term in the S-matrix expansion of above-threshold ionization is presented for the case when the binding potential is the unscreened Coulomb potential. Technical problems related to the divergence of the Coulomb scattering amplitude are avoided in the theory by considering the depletion of the atomic ground state due to the applied laser field, which is well defined and does not require the introduction of a screening constant. We focus on the low-energy structure, which was observed in recent experiments with a midinfrared wavelength laser field. Both the spectra and, in particular, the observed scaling versus the Keldysh parameter and the ponderomotive energy are reproduced. The theory provides evidence that the origin of the structure lies in the long-range Coulomb interaction.

9.
Phys Rev E ; 107(5-2): 055207, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37328980

RESUMEN

The resonance-absorption condition in the laser-nanoplasma interactions has been considered to follow the wavelength dependence of the critical plasma density. We experimentally demonstrate that this assumption fails in the middle-infrared spectral range, while it is valid for visible and near-infrared wavelengths. A thorough analysis supported by molecular dynamic (MD) simulations indicates that the observed transition in the resonance condition is caused by the reduction of the electron scattering rate and the associated increase of the cluster outer-ionization contribution. An expression for the nanoplasma resonance density is derived based on experimental results and MD simulations. The findings are important for a broad range of plasma experiments and applications, since the extension of the laser-plasma interaction studies to longer wavelengths has become increasingly topical.


Asunto(s)
Rayos Láser , Luz , Simulación de Dinámica Molecular
10.
Phys Rev Lett ; 108(3): 033002, 2012 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-22400735

RESUMEN

Intense, 100 fs laser pulses at 3.2 and 3.6 µm are used to generate, by multiphoton ionization, broadband wave packets with up to 400 eV of kinetic energy and charge states up to Xe(+6). The multiple ionization pathways are well described by a white electron wave packet and field-free inelastic cross sections, averaged over the intensity-dependent energy distribution for (e, ne) electron impact ionization. The analysis also suggests a contribution from a 4d core excitation, or giant resonance, in xenon.

11.
Phys Rev Lett ; 106(8): 083002, 2011 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-21405568

RESUMEN

The nonlinear absorption mechanisms of neon atoms to intense, femtosecond kilovolt x rays are investigated. The production of Ne(9+) is observed at x-ray frequencies below the Ne(8+), 1s(2) absorption edge and demonstrates a clear quadratic dependence on fluence. Theoretical analysis shows that the production is a combination of the two-photon ionization of Ne(8+) ground state and a high-order sequential process involving single-photon production and ionization of transient excited states on a time scale faster than the Auger decay. We find that the nonlinear direct two-photon ionization cross section is orders of magnitude higher than expected from previous calculations.

12.
Thorax ; 65(9): 815-8, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20805178

RESUMEN

BACKGROUND: Postoperative pulmonary complications (PPC) are the most frequently observed complications following lung resection, of which pneumonia and atelectasis are the most common. PPCs have a significant clinical and economic impact associated with increased observed number of deaths, morbidity, length of stay and associated cost. The aim of this study was to assess the incidence and impact of PPCs and to identify potentially modifiable independent risk factors. METHODS: A prospective observational study was carried out on all patients following lung resection via thoracotomy in a regional thoracic centre over 13 months. PPC was assessed using a scoring system based on chest x-ray, raised white cell count, fever, microbiology, purulent sputum and oxygen saturations. RESULTS: Thirty-four of 234 subjects (14.5%) had clinical evidence of PPC. The PPC patient group had a significantly longer length of stay (LOS) in hospital, high dependency unit (HDU) LOS, higher frequency of intensive care unit (ITU) admission and a higher number of hospital deaths. Older patients, body mass index (BMI) > or =30 kg/m(2), preoperative activity <400 m, American Society of Anesthesiologists (ASA) score > or =3, smoking history, chronic obstructive pulmonary disease (COPD), lower preoperative forced expiratory volume in 1 s (FEV(1)) and predicted postoperative (PPO) FEV(1) were all significantly (p<0.05) associated with PPC on univariate analysis. Multivariate analysis confirmed that age >75 years, BMI > or =30 kg/m(2), ASA > or =3, smoking history and COPD were significant independent risk factors in the development of PPC (p<0.05). CONCLUSION: The clinical impact of PPCs is marked. Significant independent preoperative risk factors have been identified in current clinical practice. Potentially modifiable risk factors include BMI, smoking status and COPD. The impact of targeted therapy requires further evaluation.


Asunto(s)
Procedimientos Quirúrgicos Torácicos/efectos adversos , Anciano , Índice de Masa Corporal , Femenino , Volumen Espiratorio Forzado , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Neumonía/etiología , Complicaciones Posoperatorias , Estudios Prospectivos , Atelectasia Pulmonar/etiología , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Factores de Riesgo , Fumar/efectos adversos
13.
Physiotherapy ; 106: 87-93, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31000366

RESUMEN

OBJECTIVES: Following major thoracic surgery physiotherapy is recommended to improve reduced lung volume, aid secretion clearance, and improve mobility, however, in many centres physiotherapy provision is variable following minimally invasive video-assisted thoracoscopic surgery (VATS). The objective of this study was to observe frequency of problems potentially amenable to physiotherapy following VATS lobectomy, and to identify associated baseline factors of patients in whom physiotherapy may be beneficial. METHODS: A prospective observational study was performed including all consecutive cancer patients undergoing VATS lobectomy in a regional centre over 4years (2012-2016). Standard postoperative care included early mobilisation by nursing staff from postoperative day one (POD1). Physiotherapy assessment of all patients on POD1 determined presence of issues potentially amenable to physiotherapy intervention, and treatment was commenced. Outcome measures included postoperative pulmonary complication (PPC) development, hospital and high dependency unit (HDU) length of stay (LOS). RESULTS: Of 285 patients, 209 (73%) received physiotherapy to assist/improve reduced mobility, of these 23 (8%) also received sputum clearance therapies and 65 (23%) specific therapy for lung volume loss. The remaining 76 (27%) patients had significantly lower hospital/HDU LOS (P<0.001) reflecting uncomplicated recovery. Chronic obstructive pulmonary disease (COPD), body mass index (BMI), preoperative mobility and age were independently associated with issues potentially amenable to physiotherapy (P=0.013). CONCLUSION: Following VATS lobectomy a large proportion of patients demonstrated issues potentially amenable to physiotherapy. The authors recommend that patients receive routine physiotherapy assessment following this type of surgery to ensure that all issues are identified early. Screening of COPD, BMI, preoperative mobility and age will allow early identification of patients who may benefit most from postoperative physiotherapy and preoperative optimisation, however, these factors cannot predict the need for physiotherapy.


Asunto(s)
Selección de Paciente , Modalidades de Fisioterapia , Cirugía Torácica Asistida por Video , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Tiempo de Internación , Pulmón/cirugía , Masculino , Persona de Mediana Edad , Cuidados Posoperatorios , Complicaciones Posoperatorias/prevención & control , Estudios Prospectivos , Factores de Riesgo
14.
Science ; 292(5522): 1689-92, 2001 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-11387467

RESUMEN

In principle, the temporal beating of superposed high harmonics obtained by focusing a femtosecond laser pulse in a gas jet can produce a train of very short intensity spikes, depending on the relative phases of the harmonics. We present a method to measure such phases through two-photon, two-color photoionization. We found that the harmonics are locked in phase and form a train of 250-attosecond pulses in the time domain. Harmonic generation may be a promising source for attosecond time-resolved measurements.

15.
Poult Sci ; 98(3): 1310-1320, 2019 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-30376070

RESUMEN

Three different regression approaches were applied to determine the optimal digestible (d.) and analyzed Val:Lys ratios for broiler performance and carcass yield. One-day-old male Cobb 500 broilers (n = 960) were assigned to 1 of 8 diets, with 6 pens/diet and 20 birds/pen, for 42 days. The negative control consisted of the basal diet with a d.Val:d.Lys ratio of 0.63 and with 93% of the required d.Lys. The positive control consisted of the basal diet with a d.Val:d.Lys of 0.80, with no reduction in d.Lys content. The other (test) diets contained a range of d.Val:d.Lys ratios, all with 93% of the required d.Lys. Data on feed intake (FI), body weight gain (BWG), and feed conversion ratio (FCR) were submitted to regression analysis, applying quadratic polynomial (QP), exponential asymptotic (EA), and linear response plateau (LRP) models. Since Val did not affect carcass or breast meat yield, no regression was performed. Digestible and analyzed Val:Lys ratios were similar based on the regression models. The intercept between the QP and LRP models was used to determine the optimum Val:Lys ratio. Overall, the ideal d.Val:d.Lys ratio will vary according to the main goal of poultry production, i.e., BWG or FCR. For BWG, the ideal ratio was found to be 0.78 (0 to 12 d), 0.73 (0 to 28 d), and 0.76 (0 to 35 or 0 to 42 d). For FCR, the optimum d.Val:d.Lys was found to be 0.80 (0 to 12 d), 0.75 (0 to 28 d), and 0.78 (0 to 35 or 0 to 42 d). The optimum analyzed Val:Lys ratio was slightly higher. For instance, for BWG the optimum ratio was 0.80 (0 to 12 d), 0.76 (0 to 28 d), and 0.79 (0 to 35 or 0 to 42 d). For FCR, the optimum Val:Lys was 0.81 (0 to 12 d), 0.79 (0 to 28 d), and 0.81 (0 to 35 or 0 to 42 d). Valine did not affect carcass or breast meat yield.


Asunto(s)
Alimentación Animal/análisis , Pollos/fisiología , Lisina/farmacología , Valina/farmacología , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Composición Corporal/efectos de los fármacos , Dieta/veterinaria , Digestión/fisiología , Lisina/administración & dosificación , Masculino , Carne/análisis , Análisis de Regresión , Valina/administración & dosificación
16.
Artículo en Inglés | MEDLINE | ID: mdl-28405433

RESUMEN

BACKGROUND: The aim of this study was to use mathematical modeling to identify and quantify the main factors that affect daily feed intake (DFI) and feed conversion ratio (FCR) in grow-finishing (GF) pig units. We evaluated the production records of 93 GF farms between 2010 and 2013, linked to a company, working in a cooperative system, located in western Paraná State, Brazil. A total of 683 batches, consisting of approximately 495,000 animals, were used. Forty production factors related to the management, health, plant and equipment, nutrition, genetics and environment were considered. The number of pigs per pen, type of feeder, origin and sex (the last two variables were combined in the models) of the animals and initial and final body weights were included in the final models to predict DFI and FCR (dependent variables). Additionally, the duration of the GF phase was included for the parameter FCR. All factors included in the final models had significant effects for both dependent variables. RESULTS: There was a reduction in DFI (0.04 kg) (P < 0.001) and an improvement in FCR (6.0 points) (P < 0.001) in batches from pens with less than 20 animals compared with batches from pens with more than 20 animals. In barns with "other" feeder types (mostly the linear dump type) different of conical semiautomatic feeder, a reduction of DFI (0.03 kg) (P < 0.05) and improved FCR (3.0 points) (P < 0.05) were observed. Batches of barrows from units specialized for producing piglets (SPU) had higher DFI (approximately 0.02 kg) (P < 0.01) than batches of females and batches of mixed animals from SPU, and batches of mixed animals from farms not specialized for piglet production (farrow-to-finish farms). Batches of females from SPU and mixed batches from SPU had better FCR (5.0 and 3.0 points respectively) (P < 0.001 and P < 0.001, respectively) than batches of piglets originating from farrow-to-finish farms. The variables selected for the final models explained approximately 50 and 64 % of the total variance in DFI and FCR, respectively. CONCLUSIONS: The models are tools for the interpretation of the factors related to the evaluated parameters, aiding in the identification of critical aspects of production. The main parameters affecting DFI and FCR in this company during the GF period were the number of pigs per pen, the type of feeder used and the combination origin-sex of the animals.

17.
J Clin Oncol ; 18(13): 2607-14, 2000 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10893293

RESUMEN

PURPOSE: To study the clinicobiologic significance of acquired 11q deletions involving the ataxia teleangiectasia locus (ATM+/-) in B-cell non-Hodgkin's lymphomas (NHL). PATIENTS AND METHODS: Fifty-three indolent lymphomas and 82 aggressive lymphomas were studied by conventional cytogenetic analysis and by fluorescence in situ hybridization using an 11q22-23 probe recognizing ATM sequences. Pertinent clinical data were collected. RESULTS: A hemizygous ATM deletion was seen in 44% to 88% of the interphase cells in 15 cases (11.1%); four patients had an indolent lymphoma (follicular center cell lymphoma), and 11 patients had an aggressive lymphoma (five mantle-cell lymphomas [MCLs] and six diffuse large-cell lymphomas). Dual-color hybridization studies showed ATM deletion to be possibly a secondary aberration in three patients with MCL. Ten out of 15 ATM+/- patients had a complex karyotype, 11 out of 15 had more than 90% abnormal metaphases (AA karyotype status), and +12, 13q14 deletion, and 17p13 deletion were seen in seven, four, and five cases, respectively. Patients with ATM+/- more frequently had a complex karyotype (P =.01) and the AA karyotype (P =.04) compared with patients without ATM+/-. With the exception of a poor performance status (P =.001), no correlation was found between ATM+/-, initial clinical variables, and complete remission rate; whereas a highly significant association was found with shorter survival (P <.0001). This cytogenetic lesion maintained its prognostic importance in multivariate analysis (P =.0004), along with performance status (P =.0006), serum lactate dehydrogenase level (P =.03), splenomegaly (P =.01), and histologic grade (P =.03). When analyzing indolent lymphomas and aggressive lymphomas separately, ATM+/- maintained its prognostic importance as an independent variable in both histologic groups (P =.0001 and P =.016, respectively). CONCLUSION: Though possibly not representing a primary genetic lesion in the majority of cases, the acquired ATM+/- status has clinicobiologic importance in NHL, possibly representing a major cytogenetic determinant of outcome.


Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 11/genética , Linfoma de Células B/genética , Proteínas Serina-Treonina Quinasas/genética , Ataxia Telangiectasia/genética , Proteínas de la Ataxia Telangiectasia Mutada , Proteínas de Ciclo Celular , Proteínas de Unión al ADN , Femenino , Marcadores Genéticos , Humanos , Hibridación Fluorescente in Situ , Interfase , Cariotipificación , Linfoma de Células B/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Proteínas Supresoras de Tumor
18.
Leukemia ; 15(12): 1841-7, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11753603

RESUMEN

At diagnosis, approximately half of myelodysplastic (MDS) patients presents a normal karyotype by conventional cytogenetic analysis (CCA). Fluorescent in situ hybridization (FISH) is more sensitive than CCA allowing for the detection of minor clones and of submicroscopic lesions. We have analyzed by FISH 101 MDS patients with normal karyotype for the occurrence of the abnormalities which are most frequently observed in MDS (ie -5/5q-, -7/7q-, +8, 17p-). In 18 patients, 15 to 32% of interphase cells were found to carry one FISH abnormality. Six patients presented trisomy 8, five had del(5)(q31), five del(7)(q31), one monosomy 7 and one del(17)(p13). FISH abnormalities were more frequently observed among patients with an increased percentage of bone marrow blasts (P = 0.001). FISH abnormalities were also associated with a higher rate of progression into AML (13/18 vs 12/83, P < 0.001) and were predictive for a worse prognosis (P < 0.001). Multivariate analysis indicated that FISH positivity and IPSS risk group were independent predictors for a poor survival (P = 0.0057 and 0.0123, respectively) and for leukemic transformation (P = 0.0006 and 0.035, respectively). Leukemic transformation in FISH-positive patients was associated in all cases with an expansion of the abnormal clone. Our data demonstrated that a significant proportion of MDS patients with normal karyotype presented, if analyzed by FISH, clones of cytogenetically abnormal cells which played a determinant role in the progression of the disease. The presence of FISH abnormalities identified a group of MDS patients with normal karyotype characterized by an inferior prognosis.


Asunto(s)
Aberraciones Cromosómicas , Análisis Citogenético/normas , Interfase , Síndromes Mielodisplásicos/genética , Adulto , Anciano , Anciano de 80 o más Años , Transformación Celular Neoplásica/genética , Células Clonales/patología , Análisis Citogenético/métodos , Progresión de la Enfermedad , Femenino , Humanos , Hibridación Fluorescente in Situ/normas , Cariotipificación , Masculino , Metafase , Persona de Mediana Edad , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/mortalidad , Pronóstico , Tasa de Supervivencia
19.
Leukemia ; 18(3): 476-83, 2004 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-14712287

RESUMEN

Cytogenetic and fluorescence in situ hybridization studies were successfully performed in 217 chronic lymphocytic leukemia (CLL). In all, 13 patients with 6q21 deletion were identified and characterized in comparison with 92 patients with 'favourable' karyotype (normal or 13q-), 69 cases with 'intermediate risk' (1-2 anomalies) and 43 cases with 'unfavourable' karyotype (complex, 11q- or 17p-). Six out of 13 cases with 6q- showed an excess of atypical lymphocytes, a finding confirmed at the histologic level; >20% CD38+ cells were seen in 5/6 cases. IGVH mutational status revealed >98% homology to the germline sequence in 4/10 cases. When compared with the 'favourable' group, patients with 6q- showed a higher white blood cell (WBC) count, frequent splenomegaly, atypical morphology, CD38+ and short time from diagnosis to first treatment and short survival. A higher median WBC count was found in the 6q- group vs the intermediate-risk group; survival was shorter in the unfavourable group. To ascertain if the 6q- anomaly was an independent factor predicting for an inferior outcome among those patients with 'favourable' cytogenetics, we performed an analysis of prognostic factors in 105 patients (92 'favourable' plus 13 with 6q-), showing that the 6q- chromosome maintained its prognostic significance at multivariate analysis (P=0.02) along with stage (P=0.01). We conclude that CLL with 6q- is characterized by a high incidence of atypical morphology, classical immunophenotype with CD38 positivity and intermediate incidence of IGVH somatic hypermutation. Clinicobiological features and outcome show that this cytogenetic subset of CLL should be allocated in an intermediate-risk category.


Asunto(s)
Cromosomas Humanos Par 6/genética , Leucemia Linfocítica Crónica de Células B/genética , ADP-Ribosil Ciclasa/genética , ADP-Ribosil Ciclasa/metabolismo , ADP-Ribosil Ciclasa 1 , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/genética , Antígenos CD/metabolismo , Femenino , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Cadenas Pesadas de Inmunoglobulina/metabolismo , Región Variable de Inmunoglobulina/genética , Región Variable de Inmunoglobulina/metabolismo , Hibridación Fluorescente in Situ , Interfase/genética , Cariotipificación , Masculino , Glicoproteínas de Membrana , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia
20.
Leukemia ; 16(9): 1745-51, 2002 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-12200689

RESUMEN

To better define the incidence and significance of cryptic chromosome lesions in acute myeloid leukemia (AML), fluorescence in situ hybridization (FISH) studies were performed in interphase cells and, when appropriate, in metaphase cells and in morphologically intact BM smears. Fifty-five adult de novo AML (group A) and 27 elderly AML or AML after myelodysplastic syndrome (AML-MDS) (group B) were tested using probes detecting the following anomalies: -5, -7, +8, deletions of 5q31, 7q31, 12p13/ETV6, 17p13/p53, 20q11. All the patients had a normal karyotype in more than 20 cells and tested negative for the common AML-associated fusion genes. No patient in group A was found to carry occult chromosome anomalies, whereas 8/27 patients in group B (P < 0.0001) showed 5q31 or 7q31 deletion (three cases each), a 17p13/p53deletion or trisomy 8 (one case each) in 33-60% interphase cells. Metaphase cells showed only one hybridization signal at 5q31 (three cases) and 7q31 (one case), whereas two normal signals at 7q31 and chromosome 8 centromeres were seen in two patients with 7q deletion and trisomy 8 in interphase cells. The majority of blast cells (76-94%) carried the chromosome anomaly in all cases; erythroid involvement in a minority of cells was seen in three patients. In group B, the presence of occult chromosome anomalies was associated with exposure to myelotoxic agents in the workplace (5/8 cases vs 3/19, P = 0.026) and with a lower complete remission rate (0/6 patients vs 7/12, P = 0.024). We arrived at the following conclusions: (1) cryptic chromosome deletions in the order of a few hundred kb magnitude may be found in a fraction of elderly AML or MDS-related AML and not in de novo adult AML with normal karyotype; (2) these chromosome lesions are usually represented by submicroscopic rearrangements; (3) they display a specific pattern of cell-lineage involvement arguing in favor of their role in the outgrowth of the leukemic blast cells; (4) they are associated with a history of exposure to myelotoxic agents in the workplace and, possibly, with resistance to induction treatment.


Asunto(s)
Linaje de la Célula/genética , Aberraciones Cromosómicas , Cromosomas Humanos Par 7/genética , Leucemia Mieloide/genética , Síndromes Mielodisplásicos/genética , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Médula Ósea/patología , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Leucemia Mieloide/patología , Persona de Mediana Edad , Síndromes Mielodisplásicos/patología , Trisomía/diagnóstico
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