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2.
Med Intensiva ; 41(3): 143-152, 2017 Apr.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27697396

RESUMO

OBJECTIVE: To study the organization of inter-hospital transport of pediatric and neonatal patients in Spain, Portugal and Latin America. DESIGN: An observational study was performed. An on-line survey was sent by email including questions about characteristics of national, regional and local health transport systems, vehicles, material, and composition of the transport team and their training. SETTING: Hospital pediatric healthcare professionals treating children in Spain, Portugal and Latin America RESULTS: A total of 117 surveys from 15 countries were analyzed. Of them, 55 (47%) come from 15 regions of Spain and the rest from Portugal and 13 Latin American countries. The inter-hospital transport of pediatric patients is unified only in the Spanish regions of Baleares and Cataluña and in Portugal. Chile has a mixed unified transport system for pediatric and adult patients. Only 51.4% of responders have an educational program for the transport personnel, and only in 36.4% of them the educational program is specific for pediatric patients. In Spain and Portugal the transport is executed mostly by public entities, while in Latin America public and private systems coexist. Specific pediatric equipment is more frequent in the transport teams in the Iberian Peninsula than in Latin American teams. The specific pediatric transport training is less frequent for teams in Latin America than on Spain and Portugal. CONCLUSIONS: There is a great variation in the organization of children transport in each country and region. Most of countries and cities do not have unified and specific teams of pediatric transport, with pediatric qualified personnel and specific material.


Assuntos
Transporte de Pacientes/organização & administração , Adolescente , Criança , Pré-Escolar , Pesquisas sobre Atenção à Saúde , Humanos , Lactente , Recém-Nascido , América Latina , Portugal , Estudos Prospectivos , Espanha
3.
J Virol ; 86(5): 2676-85, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22205739

RESUMO

Enterovirus 71 (EV71) is responsible for frequent large-scale outbreaks of hand, foot, and mouth disease worldwide and represent a major etiological agent of severe, sometimes fatal neurological disease. EV71 variants have been classified into three genogroups (GgA, GgB, and GgC), and the latter two are further subdivided into subgenogroups B1 to B5 and C1 to C5. To investigate the dual roles of recombination and evolution in the epidemiology and transmission of EV71 worldwide, we performed a large-scale genetic analysis of isolates (n = 308) collected from 19 countries worldwide over a 40-year period. A series of recombination events occurred over this period, which have been identified through incongruities in sequence grouping between the VP1 and 3Dpol regions. Eleven 3Dpol clades were identified, each specific to EV71 and associated with specific subgenogroups but interspersed phylogenetically with clades of coxsackievirus A16 and other EV species A serotypes. The likelihood of recombination increased with VP1 sequence divergence; mean half-lives for EV71 recombinant forms (RFs) of 6 and 9 years for GgB and GgC overlapped with those observed for the EV-B serotypes, echovirus 9 (E9), E30, and E11, respectively (1.3 to 9.8 years). Furthermore, within genogroups, sporadic recombination events occurred, such as the linkage of two B4 variants to RF-W instead of RF-A and of two C4 variants to RF-H. Intriguingly, recombination events occurred as a founding event of most subgenogroups immediately preceding their lineage expansion and global emergence. The possibility that recombination contributed to their subsequent spread through improved fitness requires further biological and immunological characterization.


Assuntos
Enterovirus Humano A/classificação , Enterovirus Humano A/genética , Infecções por Enterovirus/virologia , Evolução Molecular , Filogenia , Recombinação Genética , Enterovirus Humano A/isolamento & purificação , Humanos , Dados de Sequência Molecular , Proteínas Virais/genética
4.
J Med Virol ; 85(11): 1975-7, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23893817

RESUMO

In order to investigate the etiology of viral neurological infections in Spain, a national study was performed in 2008. The results obtained have been published. Enteroviruses were the most frequent cause of the aseptic meningitis and infant febrile syndromes. The present report supplements the previous study with the genotyping of the detected enteroviruses. Typing was by amplification of partial VP1 region and sequencing in 70 (53%) of the 132 available cerebrospinal fluid samples positive for enteroviruses. Twelve different genotypes within the B species were identified. Echovirus 4 was predominant (24%), followed by echovirus 30 (19%), echovirus 9 (17%), and echovirus 6 (14%). In summary, a co-circulation of several enterovirus types associated with meningitis in children under 15 years old was observed. Although infrequently detected, echovirus 4 was the predominant genotype identified due to an aseptic meningitis outbreak which occurred in the Canary Islands in 2008.


Assuntos
Infecções por Enterovirus/virologia , Enterovirus/classificação , Enterovirus/genética , Meningite Asséptica/virologia , Adolescente , Adulto , Líquido Cefalorraquidiano/virologia , Criança , Pré-Escolar , Enterovirus/isolamento & purificação , Infecções por Enterovirus/epidemiologia , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Meningite Asséptica/epidemiologia , Pessoa de Meia-Idade , Prevalência , RNA Viral/genética , Análise de Sequência de DNA , Espanha/epidemiologia , Proteínas Estruturais Virais/genética , Adulto Jovem
5.
J Med Virol ; 85(3): 554-62, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23239485

RESUMO

The aim of the study was to determine the incidence of viruses causing aseptic meningitis, meningoencephalitis, and encephalitis in Spain. This was a prospective study, in collaboration with 17 Spanish hospitals, including 581 cases (CSF from all and sera from 280): meningitis (340), meningoencephalitis (91), encephalitis (76), febrile syndrome (7), other neurological disorders (32), and 35 cases without clinical information. CSF were assayed by PCR for enterovirus (EV), herpesvirus (herpes simplex [HSV], varicella-zoster [VZV], cytomegalovirus [CMV], Epstein-Barr [EBV], and human herpes virus-6 [HHV-6]), mumps (MV), Toscana virus (TOSV), adenovirus (HAdV), lymphocytic choriomeningitis virus (LCMV), West Nile virus (WNV), and rabies. Serology was undertaken when methodology was available. Amongst meningitis cases, 57.1% were characterized; EV was the most frequent (76.8%), followed by VZV (10.3%) and HSV (3.1%; HSV-1: 1.6%; HSV-2: 1.0%, HSV non-typed: 0.5%). Cases due to CMV, EBV, HHV-6, MV, TOSV, HAdV, and LCMV were also detected. For meningoencephalitis, 40.7% of cases were diagnosed, HSV-1 (43.2%) and VZV (27.0%) being the most frequent agents, while cases associated with HSV-2, EV, CMV, MV, and LCMV were also detected. For encephalitis, 27.6% of cases were caused by HSV-1 (71.4%), VZV (19.1%), or EV (9.5%). Other positive neurological syndromes included cerebellitis (EV and HAdV), seizures (HSV), demyelinating disease (HSV-1 and HHV-6), myelopathy (VZV), and polyradiculoneuritis (HSV). No rabies or WNV cases were identified. EVs are the most frequent cause of meningitis, as is HSV for meningoencephalitis and encephalitis. A significant number of cases (42.9% meningitis, 59.3% meningoencephalitis, 72.4% encephalitis) still have no etiological diagnosis.


Assuntos
Infecções do Sistema Nervoso Central/epidemiologia , Infecções do Sistema Nervoso Central/virologia , Viroses/epidemiologia , Viroses/virologia , Vírus/isolamento & purificação , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha/epidemiologia , Vírus/classificação , Adulto Jovem
6.
J Virol ; 84(18): 9292-300, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20610722

RESUMO

The relationship between virus evolution and recombination in species B human enteroviruses was investigated through large-scale genetic analysis of echovirus type 9 (E9) and E11 isolates (n = 85 and 116) from 16 European, African, and Asian countries between 1995 and 2008. Cluster 1 E9 isolates and genotype D5 and A E11 isolates showed evidence of frequent recombination between the VP1 and 3Dpol regions, the latter falling into 23 (E9) and 43 (E11) clades interspersed phylogenetically with 46 3Dpol clades of E30 and with those of other species B serotypes. Remarkably, only 2 of the 112 3Dpol clades were shared by more than one serotype (E11 and E30), demonstrating an extremely large and genetically heterogeneous recombination pool of species B nonstructural-region variants. The likelihood of recombination increased with geographical separation and time, and both were correlated with VP1 divergence, whose substitution rates allowed recombination half-lives of 1.3, 9.8, and 3.1 years, respectively, for E9, E11, and E30 to be calculated. These marked differences in recombination dynamics matched epidemiological patterns of periodic epidemic cycles of 2 to 3 (E9) and 5 to 6 (E30) years and the longer-term endemic pattern of E11 infections. Phylotemporal analysis using a Bayesian Markov chain Monte Carlo method, which placed recombination events within the evolutionary reconstruction of VP1, showed a close relationship with VP1 lineage expansion, with defined recombination events that correlated with their epidemiological periodicity. Whether recombination events contribute directly to changes in transmissibility that drive epidemic behavior or occur stochastically during periodic population bottlenecks is an unresolved issue vital to future understanding of enterovirus molecular epidemiology and pathogenesis.


Assuntos
Enterovirus Humano B/classificação , Enterovirus Humano B/genética , Infecções por Enterovirus/epidemiologia , Infecções por Enterovirus/virologia , Evolução Molecular , Recombinação Genética , África/epidemiologia , Ásia/epidemiologia , Análise por Conglomerados , Enterovirus Humano B/isolamento & purificação , Europa (Continente)/epidemiologia , Genótipo , Geografia , Humanos , Epidemiologia Molecular , Dados de Sequência Molecular , RNA Viral/genética , Homologia de Sequência , Fatores de Tempo
7.
J Virol ; 83(5): 2109-18, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19091869

RESUMO

Globally, echovirus 30 (E30) is one of the most frequently identified enteroviruses and a major cause of meningitis. Despite its wide distribution, little is known about its transmission networks or the dynamics of its recombination and geographical spread. To address this, we have conducted an extensive molecular epidemiology and evolutionary study of E30 isolates collected over 8 years from a geographically wide sample base (11 European countries, Asia, and Australia). 3Dpol sequences fell into several distinct phylogenetic groups, interspersed with other species B serotypes, enabling E30 isolates to be classified into 38 recombinant forms (RFs). Substitutions in VP1 and 3Dpol regions occurred predominantly at synonymous sites (ratio of nonsynonymous to synonymous substitutions, 0.05) with VP1 showing a rapid substitution rate of 8.3 x 10(-3) substitutions per site per year. Recombination frequency was tightly correlated with VP1 divergence; viruses differing by evolutionary distances of >0.1 (or 6 years divergent evolution) almost invariably (>97%) had different 3Dpol groups. Frequencies of shared 3Dpol groups additionally correlated with geographical distances, with Europe and South Asia showing turnover of entirely distinct virus populations. Population turnover of E30 was characterized by repeated cycles of emergence, dominance, and disappearance of individual RFs over periods of 3 to 5 years, although the existence and nature of evolutionary selection underlying these population replacements remain unclear. The occurrence of frequent "sporadic" recombinants embedded within VP1 groupings of other RFs and the much greater number of 3Dpol groups than separately identifiable VP1 lineages suggest frequent recombination with an external diverse reservoir of non-E30 viruses.


Assuntos
Infecções por Echovirus/epidemiologia , Enterovirus Humano B/genética , Evolução Molecular , Epidemiologia Molecular , Ásia/epidemiologia , Austrália/epidemiologia , DNA Viral/genética , Infecções por Echovirus/virologia , Enterovirus Humano B/classificação , Europa (Continente)/epidemiologia , Variação Genética , Genoma Viral , Geografia , Humanos , Filogenia , Recombinação Genética , Análise de Sequência de DNA , Proteínas Estruturais Virais/genética
8.
Epidemiol Infect ; 138(12): 1775-8, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20854714

RESUMO

Few reports exist regarding the association between onychomadesis and an enterovirus infection presenting clinically as hand, foot, and mouth disease (HFMD). In February 2009, an outbreak of HFMD occurred in a Spanish nursery school, followed by onychomadesis 36-69 days later. Twelve of 17 children with HFMD developed nail shedding; enterovirus was detected in stool samples from eight (47%) of the 17. However, in only three of the children could an enterovirus serotype coxsackievirus B1 be identified. The epidemiological results of this study confirm onychomadesis as a complication in HFMD. In future outbreaks, molecular characterization of enterovirus from appropriate clinical samples should be studied.


Assuntos
Surtos de Doenças , Doença de Mão, Pé e Boca/complicações , Doença de Mão, Pé e Boca/epidemiologia , Doenças da Unha/epidemiologia , Adulto , Pré-Escolar , Análise por Conglomerados , Enterovirus Humano B/isolamento & purificação , Fezes/virologia , Humanos , Lactente , Dados de Sequência Molecular , Doenças da Unha/etiologia , Filogenia , RNA Viral/genética , Análise de Sequência de DNA , Homologia de Sequência , Espanha/epidemiologia
9.
Rev Neurol ; 64(s03): S35-S38, 2017 May 17.
Artigo em Espanhol | MEDLINE | ID: mdl-28524217

RESUMO

Enteroviruses are among the most common human viruses around the world. More than 100 different serotypes that can cause a range of clinical pathologies have been identified, although the most frequent are those that affect the central nervous system, such as aseptic meningitis, encephalitis or paralysis, which in some cases can be very severe or even fatal. In recent years, enterovirus outbreaks associated to new diseases have been reported all over the world, and as a result some serotypes have been considered 'emerging' pathogens. Yet, our knowledge about these viruses, especially about the non-polio enteroviruses that produce neuropathologies, is still limited. Surveillance systems are crucial to understand the epidemiology of the infections due to enterovirus and to be able to take appropriate action to deal with future outbreaks or epidemics.


TITLE: Importancia de los enterovirus en neuropediatria: de los poliovirus a otros enterovirus.Los enterovirus son unos de los virus humanos mas comunes en todo el mundo. Se han identificado mas de 100 serotipos distintos que pueden causar diversas patologias clinicas, aunque las mas frecuentes son las que afectan al sistema nervioso central, como meningitis aseptica, encefalitis o paralisis, que en algunos casos pueden ser muy graves e incluso mortales. En los ultimos años, se han descrito brotes por enterovirus asociados a nuevas enfermedades en todo el mundo, de tal manera que algunos serotipos se consideran patogenos 'emergentes'. Sin embargo, el conocimiento que tenemos sobre estos virus, especialmente sobre los enterovirus no polio que producen neuropatologias, todavia es limitado. Los sistemas de vigilancia resultan fundamentales para entender la epidemiologia de las infecciones por enterovirus y poder prevenir y actuar frente a futuros brotes o epidemias.


Assuntos
Infecções por Enterovirus/epidemiologia , Adolescente , Criança , Pré-Escolar , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/virologia , Surtos de Doenças , Enterovirus/classificação , Enterovirus/genética , Enterovirus/isolamento & purificação , Enterovirus/patogenicidade , Infecções por Enterovirus/virologia , Europa (Continente)/epidemiologia , Humanos , Lactente , Poliomielite/virologia , Poliovirus/isolamento & purificação , Poliovirus/patogenicidade , Vigilância da População , Sorotipagem , Espanha/epidemiologia , Estados Unidos/epidemiologia , Tropismo Viral
10.
Clin Microbiol Infect ; 23(11): 874-881, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28344164

RESUMO

OBJECTIVES: To describe the characteristics of an outbreak of brainstem encephalitis and encephalomyelitis related to enterovirus (EV) infection in Catalonia (Spain), a setting in which these manifestations were uncommon. METHODS: Clinical and microbiological data were analysed from patients with neurological symptoms associated with EV detection admitted to a reference paediatric hospital between April and June 2016. RESULTS: Fifty-seven patients were included. Median age was 27.7 months (p25-p75 17.1-37.6). Forty-one (72%) were diagnosed with brainstem encephalitis, seven (12%) with aseptic meningitis, six (11%) with encephalitis, and three (5%) with encephalomyelitis (two out of three with cardiopulmonary failure). Fever, lethargy, and myoclonic jerks were the most common symptoms. Age younger than 12 months, higher white-blood-cell count, and higher procalcitonin levels were associated with cardiopulmonary failure. Using a PAN-EV real-time PCR, EV was detected in faeces and/or nasopharyngeal aspirate in all the patients, but it was found in cerebrospinal fluid only in patients with aseptic meningitis. EV was genotyped in 47 out of 57 and EV-A71 was identified in 40 out of 47, being the only EV type found in patients with brainstem symptoms. Most of the detected EV-A71 strains were subgenogroup C1. Intravenous immunoglobulins were used in 34 patients. Eight cases (14%) were admitted to the intensive care unit. All the patients but three, those with encephalomyelitis, showed a good clinical course and had no significant sequelae. No deaths occurred. CONCLUSIONS: The 2016 outbreak of brainstem encephalitis in Catalonia was associated with EV-A71 subgenogroup C1. Despite the clinical manifestations of serious disease, a favourable outcome was observed in the majority of patients.


Assuntos
Tronco Encefálico/virologia , Surtos de Doenças/estatística & dados numéricos , Encefalite Viral , Enterovirus Humano A/genética , Infecções por Enterovirus , Anti-Inflamatórios/uso terapêutico , Pré-Escolar , Encefalite Viral/epidemiologia , Encefalite Viral/fisiopatologia , Encefalite Viral/terapia , Encefalite Viral/virologia , Infecções por Enterovirus/epidemiologia , Infecções por Enterovirus/fisiopatologia , Infecções por Enterovirus/terapia , Infecções por Enterovirus/virologia , Feminino , Humanos , Lactente , Masculino , Epidemiologia Molecular , Espanha/epidemiologia
11.
Nutr Hosp ; 21(3): 362-8, 2006.
Artigo em Espanhol | MEDLINE | ID: mdl-16771119

RESUMO

BACKGROUND: The anthropometric development in the first two years of life can be influenced by diverse factors, being analyzed in this study the implication of the primary tooth eruption and the breast feeding duration in this development. METHODS: Longitudinal study. 141 healthy children participated (67 boys and 74 girls), being analyzed the association among the duration of breast feeding, the number of teeth present at the 6, 7, 9 and 12 months, the anthropometrics parameters weight, height and body mass index (BMI) to the birth, 1-7, 9, 12, 15, 18 and 24 months and the growth rate. RESULTS: The weight and height at the birth or the duration of breast feeding didn't associate significantly with the weight and height at the 2 years or the number of teeth at 6,7,9 or 12 months, but the women with more weight (r = 0,366) and height (r = 0,377) at month of life have a bigger number of teeth at 9 months (p = 0,001). In both sexes, the number of teeth at the 9 months are associated significantly with the weight (boys r = 0,328, p = 0,01; girls r = 0,307, p = 0,011) and height (r = 0,352 boys and girls p = 0,005) at two years. CONCLUSIONS: In healthy children the duration of maternal nursing doesn't influence in the degree of anthropometric development reached at 2 years, but yes makes it the number of teeth present at 9 months, result that suggests that the eruption dental early could suppose an evolutive advantage.


Assuntos
Tamanho Corporal , Peso Corporal , Aleitamento Materno , Desenvolvimento Infantil/fisiologia , Erupção Dentária/fisiologia , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Fatores de Tempo
12.
J Clin Oncol ; 17(1): 12-8, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10458212

RESUMO

PURPOSE: We conducted a randomized trial to compare gemcitabine-cisplatin with etoposide-cisplatin in the treatment of patients with advanced non-small-cell lung cancer (NSCLC). The primary end point of the comparison was response rate. PATIENTS AND METHODS: A total of 135 chemotherapy-naive patients with advanced NSCLC were randomized to receive either gemcitabine 1,250 mg/m2 intravenously (IV) days 1 and 8 or etoposide 100 mg/m2 IV days 1 to 3 along with cisplatin 100 mg/m2 IV day 1. Both treatments were administered in 21-day cycles. One hundred thirty-three patients were included in the intent-to-treat analysis of response. RESULTS: The response rate (externally validated) for patients given gemcitabine-cisplatin was superior to that for patients given etoposide-cisplatin (40.6% v 21.9%; P = .02). This superior response rate was associated with a significant delay in time to disease progression (6.9 months v 4.3 months; P = .01) without an impairment in quality of life (QOL). There was no statistically significant difference in survival time between both arms (8.7 months for gemcitabine-cisplatin v 7.2 months for etoposide-cisplatin; P = .18). The overall toxicity profile for both combinations of drugs was similar. Nausea and vomiting were reported more frequently in the gemcitabine arm than in the etoposide arm. However, the difference was not significant. Gemcitabine-cisplatin produced less grade 3 alopecia (13% v 51%) and less grade 4 neutropenia (28% v 56% ) but more grade 3 and 4 thrombocytopenia (56% v 13%) than did etoposide-cisplatin. However, there were no thrombocytopenia-related complications in the gemcitabine arm. CONCLUSION: Compared with etoposide-cisplatin, gemcitabine-cisplatin provides a significantly higher response rate and a delay in disease progression without impairing QOL in patients with advanced NSCLC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Progressão da Doença , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Taxa de Sobrevida , Gencitabina
13.
Clin Cancer Res ; 3(7): 1229-35, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9815804

RESUMO

We investigated the clinical implications of allelic deletions at three common sites of loss of heterozygosity (LOH) in regions 5q21, 11p15.5, and 11p13 in 86 patients with non-small cell lung cancer (NSCLC). We performed a PCR-based microsatellite polymorphism assay for detection of LOH. The microsatellite markers used were D5S82 (proximal to the APC gene), MCC (within the MCC gene), D11S904 (11p13), HRAS (within the H-ras gene), and D11S860 (11p15.5). Of the 68 informative cases at 5q21 loci, LOH was found in 14 cases (20%), whereas LOH frequency in 11p15.5 and 11p13 was 31% (19 of 61 informative cases) and 19% (12 of 63 informative cases), respectively. There was a significant correlation between 5q21 LOH and mediastinal lymph node involvement (P = 0.03). However, no differences were observed in median survival times (26 months in patients with 5q21 LOH versus 37 months in the remainder; P = 0.33) nor in patients with 11p LOH (38 months versus 32 months, respectively; P = 0.72). Cox's proportional hazards model predicted that stage was the only independent poor prognostic marker in the entire cohort of NSCLC patients. Thus, the present study revealed two important abnormalities, LOH at chromosome 5q21 and LOH at chromosome 11p, both implied in NSCLC development.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 5 , Perda de Heterozigosidade , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Repetições de Microssatélites , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Mapeamento Cromossômico , Feminino , Marcadores Genéticos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Prognóstico , Análise de Sobrevida , Fatores de Tempo
14.
Clin Cancer Res ; 4(11): 2723-8, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9829735

RESUMO

Paclitaxel and etoposide are two chemotherapy agents with broad cytotoxic activity and different mechanisms of action and resistance. Preclinical studies of their combined cytotoxicity have yielded conflicting results. We performed two sequential Phase II trials using different sequence schedules of paclitaxel and etoposide as first-line treatment in advanced non-small cell lung cancer (NSCLC). Forty-four patients with stage IIIB or IV NSCLC were included between July 1995 and September 1996. All patients received etoposide at 100 mg/m2, given as an i.v. infusion on days 1, 2, and 3. The first 20 patients (part A) also received paclitaxel at 175 mg/m2 as a 3-h infusion on day 1, immediately prior to etoposide. The subsequent 24 patients (part B) were given the same paclitaxel dose, but on day 4. Grade 3-4 granulocytopenia was seen in 70% of the patients in part A and in 37% of those in part B (P = 0.04). Twenty-five % of the courses in part A and 4% of the courses in part B were associated with granulocyte nadir < or =500/microl (P = 0.00006). No responses were observed in part A, although disease was stabilized in 14 patients (70%). In part B, there were two complete responses and seven partial responses, for an overall response rate of 37.5% (95% confidence interval, 21-58%). In conclusion, toxicity and antitumor activity of the paclitaxel/etoposide combination may be sequence dependent. Our findings suggest that etoposide followed by paclitaxel is well tolerated and has greater activity in NSCLC than concurrent administration.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Etoposídeo/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/uso terapêutico , Adulto , Idoso , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Esquema de Medicação , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Resultado do Tratamento
15.
Semin Oncol ; 24(4 Suppl 12): S12-56-S12-60, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9331123

RESUMO

Studies conducted by the Spanish Lung Cancer Group indicate that cisplatin- or carboplatin-based chemotherapy can yield a 25% response rate, 9-month median survival time, and 30% 1-year survival rate in patients with stage III and IV non-small cell lung cancer. Phase II trials of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) have an almost 30% response rate in non-small cell lung cancer. Based on these results, we decided to examine whether the sequence-dependent effects of paclitaxel/etoposide influence treatment outcome (antitumor response) and toxicity. In vitro data show a paradoxical antagonist rather than additive effect. In the first part of our study (part A), paclitaxel and etoposide were administered at the same time. In the second part (part B), etoposide preceded paclitaxel. In both parts, patients with previously untreated stage IIIB or IV non-small cell lung cancer with good performance status were eligible. In part A, etoposide (fixed dose, 100 mg/m2) on days 1, 2, and 3 was administered by 30-minute infusion; paclitaxel (175 mg/m2) was given by a 3-hour infusion on day 1. In part B, the etoposide dose and schedule were the same, but paclitaxel (same dose) was administered on day 4. Treatment in both parts was repeated every 21 days for a maximum of 10 cycles. In part A, 18 patients were entered and no objective responses were observed. In part B, 21 patients were accrued, 17 of whom had sufficient follow-up for response assessment. Seven objective responses were achieved (two complete and five partial responses, for an objective response rate of 41%). Seven patients had no change and three had progressive disease. Frequency and severity of side effects were not significantly different in either part of the study. However, grade 4 neutropenia was observed in 10 (59%) patients and one (5%) patient in parts A and B of the trial, respectively. Nonhematologic toxicity was slight. In conclusion, paclitaxel cytotoxicity is abrogated when it is given concurrently with etoposide. When etoposide precedes paclitaxel, a more effective paclitaxel/etoposide schedule is attained.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/administração & dosagem , Adulto , Idoso , Esquema de Medicação , Etoposídeo/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
J Dent Res ; 78(9): 1554-9, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10512390

RESUMO

Adhesion of restorative and protective materials to dentin is an important requirement for operative and preventive dentistry. Wettability and roughness are dentin substrate conditions that are critical to establishing good adhesion. This study examined superficial and deep dentin for variations in water contact angle measurements and roughness for polished, etched, dehydrated, and rehydrated states. Superficial and deep dentin disks from 6 non-carious third molars were prepared for AFM (Atomic Force Microscope) observation, roughness measurement, and contact angle measurements following specific treatments: hydrated and polished, etched (10% H3PO4), dehydrated (desiccator for 24 hrs); and rehydrated (in water for 24 hrs). Contact angles were measured by means of the ADSA (Axisymmetric Drop Shape Analysis) technique with filtered and purified water of surface tension 72.79 ergs/cm2. The AFM was used to quantify the intertubular roughness. Mean and SD of roughness and contact angle were calculated for each dentin state, and two-way Repeated Measures ANOVA with Tukey's HSD multiple comparisons were performed at p < 0.05. Wetting and roughness both increased after etching, with roughness tending to increase further while wettability dramatically decreased after desiccation. After rehydration, water contact angle values were equivalent to those of the etched condition. Although intertubular roughness did not depend on depth, lower water contact angles were found for deep dentin. Depth and dehydration resulted in altered dentin substrates with exposed hydrophobic moieties that could interfere with bonding to hydrophilic primer coats.


Assuntos
Colagem Dentária , Dentina , Condicionamento Ácido do Dente , Análise de Variância , Dentina/química , Dentina/ultraestrutura , Dessecação , Humanos , Microscopia de Força Atômica , Propriedades de Superfície , Água , Molhabilidade
17.
Med Clin (Barc) ; 109(1): 1-5, 1997 May 31.
Artigo em Espanhol | MEDLINE | ID: mdl-9303970

RESUMO

BACKGROUND: Loss of heterozygosity (LOH) at 5q21, where the APC/MCC genes reside, is one of the genetic alterations that characterizes lung cancer. The aim of this study was to analyse LOH frequency on chromosome 5q21 in patients with non-small cell lung cancer and its relationship with TNM staging and histological subtypes. PATIENTS AND METHODS: Tumor and corresponding normal DNA were isolated from 60 patients with non-small cell lung cancer and a subsequent polymerase chain reaction (PCR) with microsatellite markets within the APC/MCC region was performed. The PCR products were resolved by electrophoresis. The comparison between the normal and tumor DNA patterns allowed us to detect the samples harboring LOH. RESULTS: LOH at 5q21 was detected in 20% of the patients. LOH at 5q21 was found in 16% of stage I patients, 8% in stage II patients and 40% in stage IIIA patients. A trend towards worse survival was detected in stage IIIA patients with LOH at 5q21 (9 months median time survival) in comparison with patients with LOH (21 months), although the difference was not statistically significant (p = 0.11). No significant differences in LOH were observed among histological types. In addition, we found no correlation between LOH and higher frequency of mutations rate affecting K-ras and p53 genes. CONCLUSIONS: LOH at 5q21 is a frequent genetic alteration in non-small cell lung cancer and correlates with locally advanced disease (stage IIIA). Our results suggest that LOH at the 5q21 region could be a prognostic factor in non-small cell lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Deleção Cromossômica , Cromossomos Humanos Par 5/genética , Heterozigoto , Neoplasias Pulmonares/genética , DNA de Neoplasias , Feminino , Genes p53/genética , Genes ras/genética , Humanos , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade
18.
Med Clin (Barc) ; 109(16): 629-31, 1997 Nov 08.
Artigo em Espanhol | MEDLINE | ID: mdl-9463138

RESUMO

To date, computed tomography is considered the best procedure to detect either relapse or residual disease in non-small cell lung cancer. However, in recent years several studies have stressed the value of F-18 fluorodeoxyglucose positron emission tomography (FDG PET) which takes advantage of the enhanced glucose uptake observed in neoplastic cells. We present the case of a patient with a locally advanced non-small cell lung cancer who received trimodal treatment with induction chemotherapy followed by surgical resection and postoperative irradiation and lately developed brain metastases which were treated with chemoradiotherapy plus radiosurgery. However a small residual lesion remained in the brain magnetic resonance. Such abnormality was evaluated by means of FDG PET which did not show any increase on FDG uptake. The present case prompt us to review the role of FDG PET as a procedure that enable to detect subclinical disease and its potential usefulness taking into account the improvement in management strategies that has been attained in non-small cell lung cancer.


Assuntos
Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão , Adulto , Biomarcadores Tumorais/sangue , Humanos , L-Lactato Desidrogenase/sangue , Neoplasias Pulmonares/sangue , Masculino , Neoplasia Residual
19.
Pharmazie ; 45(11): 844-6, 1990 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-2100337

RESUMO

The solubility of urea in different polar solvents was studied by means of determination of their dielectric constants. The most appropriate solvents turned out to be water and a water/propylene glycol (1:1 in volume) mixture. The best solvents were then used in the study of different semisolid vehicles for topical use (cetylic excipient, Beeler's base and Carbopol gel), which show different physicochemical characteristics. The final formulation contained a 40% (w/w) concentration in urea, since this value is most often used in Dermatology and, at the same time, it is the most problematic from a technological point of view. The stability of the different preparations was investigated by conductimetric and rheological determinations. The results are discussed in terms of both the solubility and stability of the active principles and the organoleptic and rheological characteristics of the final preparations.


Assuntos
Ureia/administração & dosagem , Resinas Acrílicas , Administração Tópica , Fenômenos Químicos , Físico-Química , Condutividade Elétrica , Pomadas , Reologia , Solventes , Ureia/química
20.
Rev Esp Salud Publica ; 72(4): 319-29, 1998.
Artigo em Espanhol | MEDLINE | ID: mdl-9810837

RESUMO

BACKGROUND: The difficulties which exist in order to value correctly the morbimortality caused by influenza during the childhood and the limitations of the proper vaccine make that the use of this vaccination is still limited in this phase. The objective of the present study is to value the adverse reactions associated to the influenza immunization in children. METHODS: Prospective study, carried out in the campaigns 92/93, 93/94 97/98 on 105 children of Navalcarnero with split-virion influenza vaccine with vaccinal strains recommended by the OMS. All the doses are administered by a nurse who also carries out the postimmunization-controls after 72 hours. The adverse reactions are valued, like the zone of injection, sex, age, the previous vaccination and the collection of data by telephone or in consultation. RESULTS: Of global form (318 doses), on a local level appears a reaction of 10.7%, in form of erythema (8.5%), induration (7.9%) and pain (only 97/98, 13.9%) and on a systemic level appears a reaction of 11.9%, in form of rhinorrhea (3.1%), general discomfort (2.5%), fever (2.5%), muscular pains (1.6%) and cough (1.6%). In a 89.5% the systemic effects disappear during the first 48 hours. In no case medical consultation was precised. CONCLUSIONS: The vaccine is safe. The adverse reactions that may appear are scarce, slight and well tolerated. There do not exist significant differences in terms of age, sex, the previous vaccination or the collection of the results by telephone or in consultation. The gluteus presents greater local reactogenicity that the deltoidal zone.


Assuntos
Vacinas contra Influenza/administração & dosagem , Adolescente , Fatores Etários , Criança , Relação Dose-Resposta a Droga , Feminino , Humanos , Esquemas de Imunização , Vacinas contra Influenza/efeitos adversos , Masculino , Espanha , Vacinação
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