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1.
Clin Lymphoma Myeloma Leuk ; 11(1): 168-71, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21856552

RESUMEN

To assess the value of bone marrow (BM) assessment by flow cytometry FCM after therapy in the clinical outcome of WM patients, we analyzed 42 WM patients who were evaluated before and after therapy. Patients were studied with a panel that always included the CD19, CD22, CD25, and κ/λ light chain immunoglobulin monoclonal antibodies. The mean of abnormal B-cells in the pre-therapeutic BM was 17.8% ± 12.1%, which decreased was after therapy to 5.4% ± 0.7% (P = .049). A linear correlation was seen between the better quality of response and the reduction in the tumor B-lymphocyte counts at the BM, since the ratio of abnormal B cells between pre and posttherapy BM was 1172.17, 221.64, 3.37, 1.03, and 0.56 for responses complete, partial, minor, stable disease and progression, respectively (P < .001). Intensive and rituximab-containing therapies correlated with deeper tumor cell reductions. Finally, the B-cell decrease correlated with the better overall and progression-free survival.


Asunto(s)
Médula Ósea/patología , Macroglobulinemia de Waldenström/diagnóstico , Macroglobulinemia de Waldenström/mortalidad , Anciano , Anciano de 80 o más Años , Antígenos CD19/metabolismo , Femenino , Citometría de Flujo , Humanos , Inmunofenotipificación , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasia Residual , Pronóstico
2.
Int J Pediatr Otorhinolaryngol ; 72(8): 1193-201, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18550180

RESUMEN

OBJECTIVE: Both transitory auditory otoemissions (TEOAE) and automated auditory brainstem responses (AABR) are considered adequate methods for universal hearing screening. The goal of this study was to compare the results obtained with each device, applying the same screening procedure. MATERIALS AND METHODS: From 2001 to 2003, all the newborns in our health area (2454 infants) were evaluated with TEOAE (ILO92, otodynamics) and all those born from 2004 to 2006 (3117) were evaluated with AABR (AccuScreen, Fischer-Zoth). The population studied included all well newborns and those admitted to neonatal intensive care units (NICU). The first screening was normally undertaken with well babies during the first 48h of life, before hospital discharge. Infants referred from this first step underwent a second screening after hospital discharge, before they were a month old. RESULTS: The results from each study group were compared and analyzed for significant differences. TEOAE screening yielded 10.2% fail results from the first screening step; AABR gave 2.6%. In the second screening step, 2% of the newborns screened with TEOAE were referred, whereas 0.32% of those screened with AABR were referred. These differences are statistically significant. CONCLUSIONS: Although AABR screening tests involve a slightly higher cost in time and money than TEOAE, the results obtained compensate this difference. AABR gives fewer false positives and a lower referral rate; the percent of infants lost during follow-up is consequently smaller. Therefore, in our environment, universal newborn auditory screening with AABR is more effective than that with TEOAE.


Asunto(s)
Audiometría de Respuesta Evocada , Trastornos de la Audición/diagnóstico , Pruebas Auditivas , Tamizaje Neonatal , Audiometría de Respuesta Evocada/economía , Potenciales Evocados Auditivos del Tronco Encefálico , Pruebas Auditivas/economía , Humanos , Recién Nacido , Tamizaje Neonatal/economía , Emisiones Otoacústicas Espontáneas
3.
Br J Haematol ; 141(2): 212-5, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18353163

RESUMEN

RAN, ZHX2 and RCBTB2 (CHC1L) expression was evaluated by quantitative real time reverse transcription polymerase chain reaction in plasma cells from 85 monoclonal gammopathies: 58 symptomatic multiple myeloma (MM) (52 untreated, six relapsed), eight smouldering MM, five monoclonal gammopathy of undetermined significance, four plasma cell leukaemias and 10 myeloid cell lines. ZHX2 was weakly expressed in high-risk/proliferative disease compared to low-risk or indolent disease. High ZHX2 expression was associated with better response and longer survival after high-dose therapy. RCBTB2 expression was weaker in hyperdiploid versus non-hyperdiploid cases while RAN was more expressed in symptomatic MM and cell lines.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Proteínas de Homeodominio/metabolismo , Mieloma Múltiple/metabolismo , Proteínas de Neoplasias/metabolismo , Factores de Transcripción/metabolismo , Factores de Edad , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Células de la Médula Ósea/metabolismo , Femenino , Expresión Génica , Perfilación de la Expresión Génica/métodos , Proteínas de Homeodominio/genética , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Proteínas de Neoplasias/genética , Paraproteinemias/tratamiento farmacológico , Paraproteinemias/metabolismo , Células Plasmáticas/metabolismo , Pronóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Factores de Transcripción/genética , Resultado del Tratamiento , Proteína de Unión al GTP ran/genética , Proteína de Unión al GTP ran/metabolismo
4.
Br J Haematol ; 127(2): 159-64, 2004 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15461621

RESUMEN

Melphalan-prednisone (MP) has been the gold standard treatment for more than 30 years in elderly multiple myeloma (MM) patients. In order to assess whether the combination of dexamethasone with melphalan (MD) could improve on the efficacy of MP, we have carried out a randomized trial comparing both treatment approaches. A total of 201 patients >/=70 years old were included in the study. The overall response rate was similar after six cycles (MP: 67.9%versus MD: 64.5%) and after 12 cycles (MP: 49.4%versus MD: 46.1%). However, the proportion of complete responses (CR) was higher in the MD arm, particularly after 12 cycles (MD: 22.4%versus MP: 9.1%; P < 0.05). There was no significant difference in event-free survival (MP: 15.9 months versus MD: 23.3 months). The median overall survival in both arms was almost identical (MP: 29.4 months versus MD: 27.2 months; P = 0.63). No significant differences in haematological toxicity were observed, but non-haematological toxicity was significantly higher in the MD arm. According to these results MP remains as the gold standard for treatment of MM and should be the reference for comparison of new therapeutic approaches involving novel agents.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Dexametasona/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Prednisona/administración & dosificación , Análisis de Regresión , Tasa de Supervivencia
5.
Int J Cancer ; 112(5): 884-9, 2004 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-15386370

RESUMEN

Although multiple myeloma (MM) is predominantly a disease of the elderly, few studies have focused on the identification of prognostic factors in this group of patients. Four hundred twenty five MM patients >65 years were uniformly treated with chemotherapy (MP or VCMP/VBAD). Multivariate analysis identified 4 factors with independent unfavorable prognostic influence: high percentage of S-phase bone marrow plasma cells (>2.5%); elevated beta(2) microglobulin (B2M) (>4 mg/L); age >80 years old; and LDH serum levels (above normal limit). The S-phase value was the most powerful independent prognostic factor to discriminate subgroups of patients with different prognosis. Thus, 3 main risk categories could be identified according to S-phase values: 3%, with median survivals of 34, 22 and 12 months, respectively (p < 0.0001). Our study also proved the value for elderly patients of the recently developed International Score System (ISS) based on B2M and albumin. Furthermore, the number of S-phase cells helped to subdivide the ISS III Group identifying a subset of patients with very poor prognosis defined by an additional high S-phase, who displayed a median survival of only 8 months. These results demonstrate that elderly patients can be accurately classified according to prognosis, which may be particularly valuable when comparing the efficacy of new treatment strategies. Moreover, our results underline the high prognostic value of proliferative activity of PC, a parameter that should be considered in routine laboratory investigations of MM.


Asunto(s)
Biomarcadores de Tumor/análisis , Proliferación Celular , Mieloma Múltiple/clasificación , Mieloma Múltiple/patología , Factores de Edad , Anciano , Anciano de 80 o más Años , Ciclo Celular , Femenino , Humanos , Masculino , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Análisis de Supervivencia
6.
Acta Otorrinolaringol Esp ; 54(5): 309-15, 2003 May.
Artículo en Español | MEDLINE | ID: mdl-12916474

RESUMEN

These are the results of the first year of the application of a universal programme for the early detection of neonatal deafness. Our objective is making a diagnosis of all the unilateral or bilateral cases of hearing loss above 35 dB HL, before the age of 6 months. The detection strategy has 2 screening phases with transient evoked otoacoustic emissions (TEOAE) and one diagnostic phase with auditory brain stem response (ABR). The ABR were carried out both on those patients that failed the TEOAE screening and on the neonates with hearing loss risk factors. Of the 1,277 living newborn babies (NB), we evaluated 94%. 3.3% of the NB showed hearing loss risk factors. 90% of the NB passed the first TEOAE in both ears and, after the second TEOAE, only 2.5% of the NB reached the diagnostic phase. We provided early detection and treatment of 0.58% of cases of bilateral severe-deep hearing loss. Finally, the results obtained are examined together with the importance of planning universal hearing screening.


Asunto(s)
Servicios de Salud del Niño/legislación & jurisprudencia , Servicios de Salud del Niño/provisión & distribución , Trastornos de la Audición/diagnóstico , Trastornos de la Audición/epidemiología , Tamizaje Neonatal , Factores de Edad , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Humanos , Recién Nacido , Emisiones Otoacústicas Espontáneas/fisiología , Prevalencia , España , Factores de Tiempo
7.
An Otorrinolaringol Ibero Am ; 30(3): 277-87, 2003.
Artículo en Español | MEDLINE | ID: mdl-12918292

RESUMEN

In coordination with the Paediatrics Department, we drew up a protocol for the "Early Detection of Hearing Loss in High-Risk Neonates" based fundamentally on the sequential application of impedanciometry and the Auditory Brain Stem Response (ABR). These are the results obtained from October 1994 to March 2001. Of the 240 children examined, we found 36 cases (15%) of severe-to-profound bilateral sensorineural hearing loss (> 60 dBs HL). 55% was associated with risk factors. However, we diagnosed only 2 of these cases of hearing loss (5.5%) using the protocol (sent by the neonatology department due to the fact that they showed hearing loss risk factors), since the rest (94.5%) came as a result of suspected hearing loss, which resulted in an average age for diagnosis of 3 years. Although the procedure used is highly sensitive and is diagnostically specific, in the light of these results, we consider it necessary to extend hearing screening to all newborn infants in order to evaluate its effectiveness in the early detection of infant deafness.


Asunto(s)
Trastornos de la Audición/epidemiología , Tamizaje Neonatal , Humanos , Recién Nacido , Factores de Riesgo
8.
Haematologica ; 86(2): 162-6, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11224485

RESUMEN

BACKGROUND AND OBJECTIVES: Molecular analysis has contributed to the identification of several non-random chromosomal translocations, such as t(15;17), t(8:21), inv(16)/t(16;16) and 11q23 abnormalities, typically associated with acute myeloid leukemia (AML). The identification of these chromosomal abnormalities helps not only to define different AML subtypes with distinct prognoses and treatments but also to monitor the disappearance of malignant cells after treatment. Recent reports suggest that the frequency of these alterations may differ according to geographic distribution. However, most of these reports focus on just one or two genetic alterations, which may lead to some selection bias. Appropriate epidemiological studies should be based on unselected consecutive series of patients in which all relevant genes are simultaneously analyzed. The aim of the present study was to explore whether or not the incidence of genetic lesions in Spanish AML patients differs from that reported in other countries. DESIGN AND METHODS: In a series of 145 consecutive un-selected adult patients with AML we simultaneously analyzed the presence of 4 genetic abnormalities, PML/RARalpha for t(15;17), AML1/ETO for t(8;21), CBFbeta/MYH11 for inv(16)/t(16;16) and rearrangements of the MLL gene for 11q23 abnormalities. AML were classified using the new World Health Organization (WHO) classification for hematologic malignancies. The techniques used were standardized according to the recommendations of the European BIOMED-1 Concerted Action. RESULTS: The PML/RARalpha transcript was present in 34 patients (23.4%) (23 were bcr1, 2 bcr2 and 9 bcr3). The AML1/ETO fusion transcript was detected in only 2 cases (1.4%) both with M2 morphology, but 29 other cases with M2 morphology were negative. CBFbeta/MYH11 transcript was present in 9 cases (6.2%) eight of them displaying M4Eo morphology. Finally, 5 cases (3.5%) showed rearrangements of theMLL gene. Our results differ from those reported from the United States and North/Central Europe, particularly regarding the incidence of t(15;17) and t(8;21) translocations. In Spain the frequency of t(15;17) is higher while that of t(8;21) is lower. INTERPRETATION AND CONCLUSIONS: These data add epidemiological information about geographic heterogeneity of such chromosome aberrations in AML and would contribute to the design of specific screening strategies adapted to the incidence in each country.


Asunto(s)
Aberraciones Cromosómicas/genética , Leucemia Mieloide Aguda/clasificación , Leucemia Mieloide Aguda/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Frecuencia de los Genes , Humanos , Incidencia , Leucemia Mieloide Aguda/epidemiología , Masculino , Persona de Mediana Edad , España/epidemiología , Organización Mundial de la Salud
9.
Hematol J ; 2(3): 146-9, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11920239

RESUMEN

INTRODUCTION: A model of a stepwise malignant transformation has been proposed for the pathogenesis of monoclonal gammopathies. In this model, cell cycle regulators play a central role as a source of genetic events; particularly, p16/INK4a gene acts as a tumoral suppressor gene and, recently, inactivation of this gene through a methylation mechanism, has been observed in multiple myeloma patients. Under the diagnosis of monoclonal gammopathies there is a broad spectrum of disorders with very different outcomes, ranging from indolent courses, such as those of monoclonal gammopathy of undetermined significance, Waldeströn macroglobulinemia and smoldering multiple myeloma, to aggressive diseases such as symptomatic MM and primary plasma cell leukemia. To the best of our knowledge, the activity of p16 gene has not been evaluated and compared in these different subtypes of monoclonal gammopathies. MATERIALS AND METHODS: The methylation status of the p16 gene was analysed in a group of 159 patients with monoclonal gammopathies (40 monoclonal gammopathy of uncertain significance, eight Waldenström Macroglobulinemia, eight smoldering multiple myeloma, 98 symptomatic multiple myeloma and five primary plasma cell leukemia) using three different assays (restriction enzymes and PCR or S-B and modification by sodium bisulphite). RESULTS: Forty-one of 98 MM patients (41.8%) as well as four of the five (80%) primary PCL patients showed methylation of the p16 gene, while none of the patients with monoclonal gammopathy of undetermined significance, Waldenström Macroglobulinemia or smoldering multiple myeloma displayed a methylation status. CONCLUSION: These findings suggest that the methylation of the p16 gene could be a relevant oncogenic event in the monoclonal gammopathies evolution being associated with the most aggressive forms.


Asunto(s)
Inhibidor p16 de la Quinasa Dependiente de Ciclina/fisiología , Metilación de ADN , Silenciador del Gen , Genes p16 , Paraproteinemias/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/deficiencia , ADN/química , ADN/efectos de los fármacos , ADN de Neoplasias/química , ADN de Neoplasias/efectos de los fármacos , Progresión de la Enfermedad , Leucemia de Células Plasmáticas/genética , Leucemia de Células Plasmáticas/patología , Mieloma Múltiple/genética , Mieloma Múltiple/patología , Proteínas de Neoplasias/deficiencia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/fisiología , Paraproteinemias/patología , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Sulfitos/farmacología , Macroglobulinemia de Waldenström/genética , Macroglobulinemia de Waldenström/patología
10.
Hematol J ; 2(4): 272-8, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11920260

RESUMEN

BACKGROUND: Melphalan and prednisone (MP) has been the standard treatment for multiple myeloma (MM) for the last 30 years. Combination chemotherapy at conventional doses has not shown a significant prolongation of survival when compared to MP. There are few data comparing conventional chemotherapy at standard doses with conventional treatment at higher doses. We present the long-term outcome of 914 patients from two randomized trials comparing three different dose intensity regimens. METHODS: From 1 January, 1985 to 31 December, 1989, 487 patients were randomized between MP (melphalan 9 mg/m(2) p.o. and prednisone 60 mg/m(2) days 1-4) and alternating VCMP (vincristine 1 mg i.v. on day 1, cyclophosphamide 500 mg/m(2) i.v. on day 1, melphalan 6 mg/m(2) p.o. on days 1-4, and prednisone 60 mg/m(2) on days 1-4) and VBAP (vincristine 1 mg i.v. on day 1, BCNU and doxorubicin 30 mg/m(2) i.v. each on day 1, and prednisone 60 mg/m(2) on days 1-4). From 1 January, 1990 to 31 May, 1994, 427 patients were randomized between VCMP/VBAP at the above detailed doses (VCMP/VBAP 'SD') and the same regimen increasing the doses of cyclophosphamide and doxorubicin from 500 to 1200 mg/m(2) and from 30 to 50 mg/m(2), respectively (VCMP/VBAP 'HD'). RESULTS: Increasing dose intensity produced a significantly higher partial response rate (31% vs 45% vs 51% for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P < 0.01). However, a significantly early death rate was observed in the HD arm (7.7, 7.5 and 12.1% for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P = 0.05). Median duration of response (20 vs 18 vs 19 months for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P = NS) and median survival (25 vs 31 vs 29 months for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P = NS) were similar in the three groups. MP produced a higher degree of thrombocytopenia than combination chemotherapy at standard (P = 0.002) or high dose (P = 0.01), this leading to a significantly higher dose reduction in the MP arm (P < 0.001 and P = 0.003 for VCMP/VBAP 'SD' and VCMP/VBAP 'HD', respectively). CONCLUSION: In these trials the response rate significantly correlated with the regimen intensity. However, no significant differences in response duration and survival were found. This highlights the limited role of conventional chemotherapy in MM and the need for further trials, aimed at determining the impact of new treatment approaches such as high-dose therapy/autotransplantation.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Carmustina/administración & dosificación , Causas de Muerte , Ciclofosfamida/administración & dosificación , Relación Dosis-Respuesta a Droga , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Prednisona/administración & dosificación , Inducción de Remisión , Análisis de Supervivencia , Tasa de Supervivencia , Vincristina/administración & dosificación
11.
Haematologica ; 85(11): 1146-52, 2000 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11064466

RESUMEN

BACKGROUND AND OBJECTIVES: Cytogenetic studies in multiple myleoma (MM) are limited by the difficulties in obtaining metaphases that can be investigated and few studies have analyzed the relationship between cytogenetics and clinical disease characteristics. The aim of our study was to analyze the recurrent cytogenetic changes in MM and to correlate them with clinical and biological characteristics including the percentage of S-phase plasma cells (PCs). DESIGN AND METHODS: Chromosomal abnormalities were analyzed in 86 patients with MM. In all patients, two types of cultures (5 d culture with interleukin-4 and unstimulated 72 h culture) were used for cytogenetic analysis. DNA content analysis (ploidy and cell cycle analysis) together with the most relevant clinical and biological disease features were studied. RESULTS: Cytogenetic analysis was successful in 72 of the 86 patients (84%). Forty-seven patients (65%) had an abnormal karyotype. The most frequent trisomies involved chromosomes 3, 5, 9, 11, 15, 19, 22, 1, 7, 17, 18, and 21, and monosomies affected chromosomes 13 and 8, while structural changes involved chromosomes 1, 11, 14q32, 4p16 and 16q22-23. Patients with abnormal karyotype displayed a poor performance status, advanced stage, anemia and a high percentage of bone marrow plasma cells. In addition, MM patients with -13/13q- and 11q abnormalities showed a significantly higher proportion of S-phase PCs (p=0.02). INTERPRETATION AND CONCLUSIONS: In summary, our study shows a relationship between unfavorable cytogenetics (-13/13q-/11q abnormalities) and a high percentage of S-phase PCs, a well-known adverse prognostic factor.


Asunto(s)
Aberraciones Cromosómicas/genética , Mieloma Múltiple/genética , Anciano , Anciano de 80 o más Años , Células de la Médula Ósea/ultraestructura , Aberraciones Cromosómicas/patología , Trastornos de los Cromosomas , Cromosomas Humanos Par 11 , Cromosomas Humanos Par 13 , Estudios de Cohortes , Análisis Citogenético , Femenino , Humanos , Cariotipificación , Masculino , Persona de Mediana Edad , Monosomía , Mieloma Múltiple/patología , Fase S , Trisomía
12.
Acta Otorrinolaringol Esp ; 51(1): 31-5, 2000.
Artículo en Español | MEDLINE | ID: mdl-10799929

RESUMEN

The protocol developed at our hospital for auditory assessment of children with risk factors for deafness is presented. The results obtained with tympanometry and auditory brainstem response (ABR) audiometry from October 1994 to March 1998 were analyzed. In 122 children, 17 cases (14%) of severe-to-profound bilateral deafness were found. Only 50% of these cases were associated with risk factors present at birth. The average age at time of diagnosis of deafness was over 3 years. In view of these results, we recommend auditory screening for all newborns as the only effective procedure for early detection of childhood deafness.


Asunto(s)
Sordera/diagnóstico , Sordera/epidemiología , Tamizaje Neonatal , Humanos , Lactante , Recién Nacido , Factores de Riesgo , Índice de Severidad de la Enfermedad
13.
Allergol Immunopathol (Madr) ; 27(1): 11-7, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10217667

RESUMEN

To asses the role of pulmonary inflammation in the outcome of preterm neonates with respiratory distress syndrome (RDS) we measured soluble intercellular adhesion molecule-1 (ICAM-1), interleukin-8 (IL-8), eosinophil cationic protein (ECP) and transforming growth factor beta-1 (TGF beta 1) in tracheobronquial lavage (TBL) fluid of 15 preterm infants; 9/15 completely recovered from RDS and 6/15 developed chronic lung disease (CLD). ICAM-1 (p: 0.001) and TGF beta 1 (p: 0.04) levels increased in TBL fluid during the first days of life. The values of ICAM-1 were correlated to the days of 0(2) and mechanical ventilation dependency. At 3 days of age, ICAM-1 levels in TBL fluid were higher in infants who later developed CLD compared to infants without CLD (24.5 vs 8.3 micrograms/ml; p: 0.02). Thereafter no significant differences were found although the CLD group had higher values. IL-8 levels showed a fall, specially from 1 to 3 days of age in children without CLD (77.0 to 41.7 ng/ml) although not significant. No difference in TGF beta 1 values were found between both groups, but the TGF beta 1 levels were lower in patients with CLD and they showed undetectable values in 8 samples. ICAM-1 is a major factor associated with airways inflammation whereas IL-8 is not a good marker during the first days of life to predict the RDS outcome. A defect of TGF beta 1 in the smallest premature infants may delay the lung repair process which occurs after tissue injury. High ICAM-1 levels and low TGF beta 1 levels in lung fluid are related to oxygen dependency at 28 days of age.


Asunto(s)
Líquido del Lavado Bronquioalveolar/química , Neumonía/complicaciones , Síndrome de Dificultad Respiratoria del Recién Nacido/patología , Ribonucleasas , Biomarcadores , Proteínas Sanguíneas/análisis , Proteínas en los Gránulos del Eosinófilo , Edad Gestacional , Humanos , Recién Nacido , Recien Nacido Prematuro , Molécula 1 de Adhesión Intercelular/análisis , Interleucina-8/análisis , Síndrome de Dificultad Respiratoria del Recién Nacido/complicaciones , Tráquea , Factor de Crecimiento Transformador beta/análisis , Resultado del Tratamiento
14.
Blood ; 93(3): 1032-7, 1999 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-9920853

RESUMEN

We report on a series of 26 patients diagnosed with primary (de novo) plasma cell (PC) leukemia (PCL) in whom we analyzed the clinicobiologic characteristics of the disease together with the immunophenotype, DNA cell content, proliferative index, and numeric chromosomal aberrations of the neoplastic PC, and compared them with 664 multiple myeloma (MM) patients at diagnosis. The median age, sex ratio, and bone lesion extension were similar, but PCL cases displayed a higher prevalence of clinical stage III, extramedullary involvement, and Bence Jones cases, with fewer IgA cases than for MM patients. In addition, according to several prognostic indicators (beta2-microglobulin serum level, proportion of S-phase PCs, proteinuria, calcium serum level, lactate dehydrogenase [LDH] and renal function), the incidence of adverse prognostic factors was significantly higher in PCL versus MM. Immunophenotypic expression was similar for CD38, CD138, CD2, CD3, CD16, CD10, CD13, and CD15, but PCL differed from MM in the expression of CD56, CD9 HLA-DR, CD117, and CD20 antigens. Twenty-two PCL cases were diploid and one was hypodiploid, while most MM cases (57%) showed DNA hyperdiploidy. With the fluorescent in situ hydridization (FISH) technique, 12 of 13 PCL cases displayed the numeric aberrations, -13 (86%), +/-1 (57%), +18 (43%), and -X in women (25%), but they lacked several numeric aberrations usually found in MM such as +3, +6, +9, +11, and +15. PCL cases had a lower overall response to therapy than MM cases (38% v 63%, P =.01332). Among PCL patients, a trend for a worse response was observed in cases treated with melphalan and prednisone (MP) versus polychemotherapy. Overall survival was significantly worse in PCL versus MM patients (8 v 36 months, P <.0001), but it was significantly better in PCL patients treated with polychemotherapy versus MP (18 v 3 months, P =.0137). By contrast, MM patients did not show significant differences in overall survival according to the treatment used, MP or polychemotherapy. Ten variables seemed to predict survival in PCL patients, but only the beta2-microglobulin level and S-phase PCs retained an independent value in multivariate analysis. In summary, our study illustrates that PCs from PCL display singular phenotypic, DNA cell content, and cytogenetic characteristics that lead to a different disease evolution versus MM.


Asunto(s)
Leucemia de Células Plasmáticas/patología , Ploidias , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Aberraciones Cromosómicas , Femenino , Humanos , Inmunofenotipificación , Leucemia de Células Plasmáticas/tratamiento farmacológico , Leucemia de Células Plasmáticas/genética , Leucemia de Células Plasmáticas/mortalidad , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Índice Mitótico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Mieloma Múltiple/mortalidad , Mieloma Múltiple/patología , Proteínas de Neoplasias/análisis , Prednisona/administración & dosificación , Pronóstico , Tasa de Supervivencia , Resultado del Tratamiento
15.
Br J Haematol ; 103(1): 137-42, 1998 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9792300

RESUMEN

The in vitro growth characteristics of a large series of acute myeloid leukaemia (AML) patients and their relationship with other clinical and biological disease characteristics were analysed. Patients with AML were studied, 181 with de novo AML and 45 with secondary AML (24 myelodysplastic syndrome, sAML-MDS, 21 myeloproliferative disorder, sAML-MPD). Leukaemic colony forming units (L-CFU) were assayed by plating peripheral blood (PB) blast cells in methyl-cellulose and using LCM-PHA as stimulant. In each case parallel cultures were made with and without stimulating factors. Plating efficiency (PE) was defined as the number of clusters plus colonies/10(5) cells plated. Autonomous growth (AG) was the number of colonies plus clusters growing without stimulant. The autonomous proliferative index (API) was calculated as the number of clusters + colonies without stimulating factor divided by the number of clusters + colonies with stimulating factor. No significant differences in the PE between de novo and secondary AML were found. Autonomous growth was significantly higher in sAML-MPD. The FAB subtype M3 leukaemias displayed a significantly greater PE and a significantly lower API when compared with the other FAB subgroups (P=0.0002). Upon analysing the relationship with the immunophenotype, only CD33 expression showed a significant relationship with the in vitro growth pattern; CD33+ cases displayed a higher PE (P=0.0002) and AG (P=0.0003) than CD33- cases. When patients were grouped according to the level of rh123 efflux (MDR1) it was observed that cases with >30% elimination showed a higher AG and API than those with <30% (P=0.03). Finally we found that patients with higher API (>0.05) displayed a significantly shorter overall survival as compared with patients with API<0.05 (P=0.04). The in vitro study properties of clonogenic cells produces relevant clinical information of leukaemic cell biology in AML patients.


Asunto(s)
Leucemia Mieloide Aguda/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , División Celular , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Células Tumorales Cultivadas
17.
Blood ; 91(9): 3366-71, 1998 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-9558394

RESUMEN

Recent observations indicate that chromosome aberrations are important prognostic factors in patients with multiple myeloma (MM) treated with high-dose chemotherapy. Nevertheless, the inherent problems of conventional cytogenetics have hampered the systematic evaluation of this parameter in series of patients treated with conventional chemotherapy. Fluorescence in situ hybridization (FISH) analysis is an attractive alternative for evaluation of numerical chromosomal changes. In the present study, we analyze the relationship between aneuploidies of 15 different chromosomes assessed by FISH and prognosis in a series of 63 patients with MM treated with conventional chemotherapy. After a median follow-up of 61 months (range, 6 to 109), 49% of patients are still alive with a median survival of 33 months. The overall incidence of numerical chromosome abnormalities was 70%. This incidence significantly increased when seven or more chromosomes were analyzed (53 patients), reaching 81%. Trisomies of chromosomes 6, 9, and 17 were associated with prolonged survival (P = .033, P = .035, and P = .026, respectively); by contrast, overall survival (OS) was lower in cases with monosomy 13 (as assessed by deletion of Rb gene, P = .0012). From the clinical point of view, loss of Rb gene was associated with a poor performance status; low hemoglobin levels; high creatinine, C-reactive protein, and lactic dehydrogenase serum levels; high percentage of bone marrow plasma cells (BMPC); extensive bone lytic lesions; and advanced clinical stage. Other chromosome abnormalities such as trisomy of chromosome 9 and 17 were associated with good prognostic features including high hemoglobin levels, early clinical stage, beta2microglobulin less than 6 micro/mL, and low percentage of BMPC. A multivariate analysis for OS showed that S-phase PC greater than 3% (P = .010) and beta2microglobulin serum levels greater than 6 micro/mL (P = .024), together with monosomy of chromosome 13 (P = .031) and nontrisomy of chromosome 6 (P = .048) was the best combination of independent parameters for predicting survival in patients with MM. According to these results, chromosomal analysis is of great use in patients with MM at diagnosis to have a correct prognostic evaluation for clinical decision making.


Asunto(s)
Mieloma Múltiple/diagnóstico , Anciano , Aneuploidia , Aberraciones Cromosómicas , Deleción Cromosómica , Cromosomas Humanos Par 13 , Cromosomas Humanos Par 6 , ADN de Neoplasias/genética , Femenino , Humanos , Inmunofenotipificación , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Mieloma Múltiple/genética , Mieloma Múltiple/patología , Análisis de Supervivencia
18.
Blood ; 90(6): 2465-70, 1997 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-9310499

RESUMEN

A high complete remission rate is currently achieved in patients with acute myeloid leukemia (AML). However, many patients eventually relapse due to the persistence of low numbers of residual leukemic cells that are undetectable by conventional cytomorphologic criteria (minimal residual disease [MRD]). Using immunophenotypic multiparametric flow cytometry, we have investigated in sequential studies (diagnosis and follow-up) the impact of MRD detection on the outcome of 53 AML patients that had achieved morphologic remission with standard AML protocols and displayed at diagnosis an aberrant phenotype. Patients were studied at diagnosis with a panel of 35 monoclonal antibodies in triple staining combinations for detection of aberrant or uncommon phenotypic features. According to these features, a patient's probe was custom-built at diagnosis for the identification of possible residual leukemic cells during follow-up. The level of MRD at the end of induction and intensification therapy correlated with the number of relapses and relapse-free survival (RFS). Thus, patients with more than 5 x 10(-3) residual cells (5 residual cells among 1,000 normal bone marrow [BM] cells) identified as leukemic by immunophenotyping in the first remission BM showed a significant higher rate of relapse (67% v 20% for patients with less than 5 x 10(-3) residual cells; P = .002) and a lower median RFS (17 months v not reached; P = .01). At the end of intensification, with a cut-off value of 2 x 10(-3) leukemic cells, AML patients also separated into two distinct groups with relapse rates of 69% versus 32% (P = .02), respectively, and median RFS of 16 months versus not reached (P = .04). In addition, overall survival was also significantly related to the level of residual cells in the marrow obtained at the end of induction and particularly after intensification therapy (P = .008). Furthermore, we have explored whether residual disease was related with the functional expression of multidrug resistance (MDR-1) at diagnosis as assessed by the rhodamine123 assay. Patients with > or =5 x 10(-3) residual leukemic cells at the end of induction therapy had a significantly higher rhodamine-123 efflux (mean, 56% +/- 24%) than those with less than 5 x 10(-3) residual cells (mean, 32% +/- 31%; P = .04). Finally, multivariate analysis showed that the number of residual cells at the end of induction or intensification therapy was the most important prognostic factor for prediction of RFS. Overall, our results show that immunophenotypical investigation of MRD strongly predicts outcome in patients with AML and that the number of residual leukemic cells correlates with multidrug resistance.


Asunto(s)
Leucemia Mieloide/diagnóstico , Neoplasia Residual/diagnóstico , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Enfermedad Aguda , Médula Ósea/patología , Resistencia a Múltiples Medicamentos , Citometría de Flujo , Humanos , Inmunofenotipificación , Leucemia Mieloide/inmunología , Evaluación de Resultado en la Atención de Salud , Pronóstico , Análisis de Supervivencia
19.
Ann Hematol ; 70(4): 189-94, 1995 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-7748963

RESUMEN

The existence of leukemic-associated phenotypes has been suggested to be a valuable tool for the detection of minimal residual disease (MRD) in AML patients, as they would allow to distinguish leukemic blast cells from normal hematopoietic progenitors. The present study was designed to analyze in which proportion of AML patients the immunological detection of MRD is feasible, based on the presence of aberrant phenotypes that allow the distinction of leukemic from normal cells. For this purpose we have prospectively investigated the blast cells from 40 AML patients at diagnosis with a large panel of MoAb in double and triple staining combinations analyzed at flow cytometry, in order to detect aberrant phenotypes on blast cells (lineage infidelity, antigenic overexpression, and asynchronous antigenic expression, as well as aberrant light-scatter pattern). In the analysis of the 40 AML cases more than one blast cell subset, distinguished by its different antigenic expression, was detected in 85% of the patients: five different phenotypic blast cell subsets were observed in six cases, four in 13 patients, three subsets in three cases, and two in 12 patients; only six cases showed a homogeneous phenotypical blast cell population. Twenty-nine of the 40 AML cases analyzed (73%) showed the existence of at least one aberrant phenotype: in 15 cases the myeloid blast cells co-expressed lymphoid-associated antigens (CD2, CD5, CD7, and/or CD19)--lineage infidelity--; asynchronous antigen expression was detected in 25 patients (CD34+CD56+, CD34+CD11b+, CD34+CD14+, CD117+CD15+, CD33-CD13+, CD13-CD15+, HLADR + CD15 , HLADR-CD14+CD11b+ CD4+); seven cases displayed antigen overexpression (CD13, CD33, CD15, or CD14); and in 13 patients leukemic cells had an abnormal FSC/SSC distribution according to their phenotype. These results suggest that immunological methods for the detection of MRD based on the existence of aberrant phenotypes could be used in the majority of AML patients.


Asunto(s)
Antígenos CD/análisis , Leucemia Mieloide Aguda/inmunología , Fenotipo , Anticuerpos Monoclonales , Citometría de Flujo , Antígenos HLA-DR/análisis , Humanos , Inmunofenotipificación , Estudios Prospectivos
20.
Rev Epidemiol Sante Publique ; 40(2): 85-92, 1992.
Artículo en Inglés | MEDLINE | ID: mdl-1631381

RESUMEN

The aim of this study was to acquire a better knowledge of the epidemiology of Lyme disease. A seroepidemiologic study was made by evaluating the different levels of antibodies to Borrelia burgdorferi in a five hundred serum representative sample of a population from the province of La Rioja, Spain. Samples were randomly selected and stratified to take into account sex, age, rural or urban residence, and geographical area. All subjects included in the study were asked to fill out a questionnaire containing this information along with data concerning leisure activities, occupation, contact with animals, tick-bite and antecedent features related to Lyme disease. No statistical differences were found in relation to sex or age. The seroprevalence was very high (31.3%) in mountain areas, where Ixodes ricinus and deer are present. The risk factors associated with seropositivity were forestry and cattle-raising activities, as well as contact with animals. The best titer of antibodies associated with clinical antecedents of Lyme disease and related disorders was 1/256.


Asunto(s)
Grupo Borrelia Burgdorferi/inmunología , Enfermedad de Lyme/epidemiología , Adolescente , Adulto , Anticuerpos Antibacterianos/aislamiento & purificación , Niño , Femenino , Humanos , Enfermedad de Lyme/inmunología , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Muestreo , Estudios Seroepidemiológicos , España/epidemiología
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