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1.
Rev Clin Esp ; 222(1): 22-30, 2022 Jan.
Artigo em Espanhol | MEDLINE | ID: mdl-34054133

RESUMO

INTRODUCTION: There is controversy regarding the best predictors of clinical deterioration in COVID-19. OBJECTIVE: This work aims to identify predictors of risk factors for deterioration in patients hospitalized due to COVID-19. METHODS DESIGN: Nested case-control study within a cohort. Setting: 13 acute care centers of the Osakidetza-Basque Health Service. Participants: Patients hospitalized for COVID-19 with clinical deterioration-defined as onset of severe ARDS, ICU admission, or death-were considered cases. Two controls were matched to each case based on age. Sociodemographic data; comorbidities; baseline treatment; symptoms; date of onset; previous consultations; and clinical, analytical, and radiological variables were collected. An explanatory model of clinical deterioration was created by means of conditional logistic regression. RESULTS: A total of 99 cases and 198 controls were included. According to the logistic regression analysis, the independent variables associated with clinical deterioration were: emergency department O2 saturation ≤90% (OR 16.6; 95%CI 4-68), pathological chest X-ray (OR 5.6; 95%CI 1.7-18.4), CRP >100 mg/dL (OR 3.62; 95%CI 1.62-8), thrombocytopenia with < 150,000 platelets (OR 4; 95%CI 1.84-8.6); and a medical history of acute myocardial infarction (OR 15.7; 95%CI, 3.29-75.09), COPD (OR 3.05; 95%CI 1.43-6.5), or HT (OR 2.21; 95%CI 1.11-4.4). The model's AUC was 0.86. On the univariate analysis, female sex and presence of dry cough and sore throat were associated with better clinical progress, but were not found to be significant on the multivariate analysis. CONCLUSION: The variables identified could be useful in clinical practice for the detection of patients at high risk of poor outcomes.

2.
Sci Total Environ ; 912: 169072, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38048997

RESUMO

The fate and behavior of herbicides can be altered in an unpredictable way when organic amendments are added to soil as a beneficial management tool. The objective of this work was to investigate the effect exerted by the addition of two different organic amendments (alperujo compost and biochar) to soil in the degradation of one of the most relevant new generation rice herbicides, profoxydim. In unamended soils, the degradation of profoxydim was quite fast and was governed by both chemical (DT50steril soil = from 1.52 to 9.21 days) and microbial (DT50nonsterile soil = from 0.47 to 0.53 days) processes. Alperujo- and biochar-amended soils significantly increased the persistence of the herbicide in both soils, especially in the presence of biochar, due to the high capacity absorption of this amendment, increasing DT90 from 1.92 to 3.54 days for DT90unamended to 41.02-48.41 days for DT90biochar amended. Different kinetics models applied to fit the observed dissipation datasets showed that a HS biphasic model fits well with the dissipation of profoxydim in amended and unamended soils. For the first time, five degradation products (DPs) were identified by HPLC-QTOF-MS/MS in soil and a degradation pathway was described. Main DP was generated via oxidation of the sulfur atom to give rise to the corresponding sulfoxide derivative, with this DP being more persistent than the active substance. These outcomes can be very useful for the assessment of the environmental risk associated with the use of profoxydim in rice crops and the application of organic amendments as potential measures for minimizing the risk of contamination of natural water resources.

3.
Food Chem ; 443: 138536, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38277930

RESUMO

A method for the simultaneous determination of the four stereoisomers of the chiral herbicide profoxydim in rice and husk was developed using the QuEChERS method and LC-tandem mass spectrometry. Four polysaccharide-based chiral stationary phase columns were evaluated. All four stereoisomers were successfully separated on a Chiracel OJ-3R column. The effects of mobile phase, modifiers, mobile phase flow rate and temperature on the separation were also investigated. Different QuEChERS methods were compared for the development of an optimized sample preparation procedure. The method, following SANTE guidelines, showed excellent linearity (R2 ≥ 0.99), the LODs were below 4.0 µg kg-1, and the LOQs did not exceed 12.5 µg kg-1. The overall average recoveries at three levels (12.5, 25.0 and 250 µg kg-1) ranged from 76.77 % to 106.53 %, with RSD values less than 7 %. The method is demonstrated to be convenient and reliable for the routine monitoring of profoxydim stereoisomers in rice and husk.


Assuntos
Derivados de Benzeno , Herbicidas , Oryza , Piranos , Cromatografia Líquida/métodos , Espectrometria de Massa com Cromatografia Líquida , Oryza/química , Estereoisomerismo , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos
4.
Sci Total Environ ; 894: 164877, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37331396

RESUMO

The relationship between exposure to air pollution and the severity of coronavirus disease 2019 (COVID-19) pneumonia and other outcomes is poorly understood. Beyond age and comorbidity, risk factors for adverse outcomes including death have been poorly studied. The main objective of our study was to examine the relationship between exposure to outdoor air pollution and the risk of death in patients with COVID-19 pneumonia using individual-level data. The secondary objective was to investigate the impact of air pollutants on gas exchange and systemic inflammation in this disease. This cohort study included 1548 patients hospitalised for COVID-19 pneumonia between February and May 2020 in one of four hospitals. Local agencies supplied daily data on environmental air pollutants (PM10, PM2.5, O3, NO2, NO and NOX) and meteorological conditions (temperature and humidity) in the year before hospital admission (from January 2019 to December 2019). Daily exposure to pollution and meteorological conditions by individual postcode of residence was estimated using geospatial Bayesian generalised additive models. The influence of air pollution on pneumonia severity was studied using generalised additive models which included: age, sex, Charlson comorbidity index, hospital, average income, air temperature and humidity, and exposure to each pollutant. Additionally, generalised additive models were generated for exploring the effect of air pollution on C-reactive protein (CRP) level and SpO2/FiO2 at admission. According to our results, both risk of COVID-19 death and CRP level increased significantly with median exposure to PM10, NO2, NO and NOX, while higher exposure to NO2, NO and NOX was associated with lower SpO2/FiO2 ratios. In conclusion, after controlling for socioeconomic, demographic and health-related variables, we found evidence of a significant positive relationship between air pollution and mortality in patients hospitalised for COVID-19 pneumonia. Additionally, inflammation (CRP) and gas exchange (SpO2/FiO2) in these patients were significantly related to exposure to air pollution.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , COVID-19 , Pneumonia , Humanos , Dióxido de Nitrogênio/análise , Teorema de Bayes , Estudos de Coortes , Poluição do Ar/análise , Poluentes Atmosféricos/análise , Pneumonia/epidemiologia , Pneumonia/induzido quimicamente , Inflamação/induzido quimicamente , Material Particulado/análise , Exposição Ambiental/análise
5.
Eur J Clin Microbiol Infect Dis ; 31(12): 3397-405, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23010902

RESUMO

The aim of the present study is to evaluate the usefulness of two biomarkers-procalcitonin (PCT) and C-reactive protein (CRP)-in addition to the CURB-65 score for assessing the site of care and the etiology of non-severe community-acquired pneumonia (CAP). We conducted a prospective observational study from April 1, 2006, to June 30, 2007, in a single teaching hospital in northern Spain among patients with non-severe CAP. In addition to collecting data needed to determine the CURB-65 score, microbial cultures were taken and levels of PCT and CRP were measured. We compared the prognostic accuracy of these biomarkers with the CURB-65 score to predict hospitalization and microbial etiology using receiver operating characteristic (ROC) curves. A total of 344 patients with non-severe CAP were enrolled; 73 were admitted to the hospital and 271 were treated on an outpatient basis. An etiologic diagnostic was made for 44 %, with atypical pathogens predominating. Levels of PCT and CRP increased with increasing CURB-65 scores. Patients admitted to the hospital had higher PCT and CRP levels than outpatients (p < 0.001). For predicting hospitalization, PCT had a better area under the ROC curve (AUC) (0.81) than the CURB-65 score alone (0.77). For PCT plus the CURB-65 score, the AUC increased significantly from 0.77 to 0.83. In patients with bacterial CAP, the biomarker levels were significantly higher than among patients with atypical or viral etiology (p < 0.001). PCT with a cut-off point of 0.15 ng/mL was the best predictor for bacterial etiology and for select patients eligible for outpatient care. In conclusion, levels of PCT and CRP positively correlate with increasing severity of CAP and may have a role in predicting both patients who can safely receive outpatient care and the microbial etiology in patients with low CURB-65 scores.


Assuntos
Biomarcadores/análise , Proteína C-Reativa/análise , Calcitonina/sangue , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/terapia , Técnicas de Apoio para a Decisão , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/terapia , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Precursores de Proteínas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial , Peptídeo Relacionado com Gene de Calcitonina , Medicina Clínica/métodos , Feminino , Hospitalização , Hospitais de Ensino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Curva ROC , Espanha
6.
Eur J Clin Microbiol Infect Dis ; 31(10): 2693-701, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22526871

RESUMO

The objective of this paper was to develop a prognostic index for severe complications among hospitalized patients with influenza A (H1N1) 2009 virus infection. We conducted a prospective observational cohort study of 618 inpatients with 2009 H1N1 virus infection admitted to 36 Spanish hospitals between July 2009 and February 2010. Risk factors evaluated included host-related factors and clinical data at admission. We developed a composite index of severe in-hospital complications (SIHC), which included: mortality, mechanical ventilation, septic shock, acute respiratory distress syndrome, and requirement for resuscitation maneuvers. Six factors were independently associated with SIHC: age >45 years, male sex, number of comorbidities, pneumonia, dyspnea, and confusion. From the ß parameter obtained in the multivariate model, a weight was assigned to each factor to compute the individual influenza risk score. The score shows an area under the receiver operating characteristic (ROC) curve of 0.77. The SIHC rate was 1.9 % in the low-risk group, 10.3 % in the intermediate-risk group, and 29.6 % in the high-risk group. The odds ratio for complications was 21.8 for the high-risk group compared with the low-risk group. This easy-to-score influenza A (H1N1) 2009 virus infection risk index accurately stratifies patients hospitalized for H1N1 virus infection into low-, intermediate-, and high-risk groups for SIHC.


Assuntos
Hospitalização , Vírus da Influenza A Subtipo H1N1/patogenicidade , Influenza Humana/diagnóstico , Índice de Gravidade de Doença , Adulto , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Comorbidade , Biologia Computacional/métodos , Feminino , Humanos , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Gravidez , Prognóstico , Estudos Prospectivos , Curva ROC , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/virologia , Fatores de Risco , Choque Séptico/virologia
7.
Rev Clin Esp (Barc) ; 222(1): 22-30, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34556435

RESUMO

INTRODUCTION: There is controversy regarding the best predictors of clinical deterioration in COVID-19. OBJECTIVE: This work aims to identify predictors of risk factors for deterioration in patients hospitalized due to COVID-19. METHODS DESIGN: Nested case-control study within a cohort. SETTING: 13 acute care centers of the Osakidetza-Basque Health Service. PARTICIPANTS: patients hospitalized for COVID-19 with clinical deterioration-defined as onset of severe ARDS, ICU admission, or death-were considered cases. Two controls were matched to each case based on age. Sociodemographic data; comorbidities; baseline treatment; symptoms; date of onset; previous consultations; and clinical, analytical, and radiological variables were collected. An explanatory model of clinical deterioration was created by means of conditional logistic regression. RESULTS: A total of 99 cases and 198 controls were included. According to the logistic regression analysis, the independent variables associated with clinical deterioration were: emergency department O2 saturation ≤90% (OR 16.6; 95%CI 4-68), pathological chest X-ray (OR 5.6; 95%CI 1.7-18.4), CRP > 100 mg/dL (OR 3.62; 95%CI 1.62-8), thrombocytopenia with <150,000 platelets (OR 4; 95%CI 1.84-8.6); and a medical history of acute myocardial infarction (OR 15.7; 95%CI, 3.29-75.09), COPD (OR 3.05; 95%CI 1.43-6.5), or HT (OR 2.21; 95%CI 1.11-4.4). The model's AUC was 0.86. On the univariate analysis, female sex and presence of dry cough and sore throat were associated with better clinical progress, but were not found to be significant on the multivariate analysis. CONCLUSION: The variables identified could be useful in clinical practice for the detection of patients at high risk of poor outcomes.


Assuntos
COVID-19 , Deterioração Clínica , Estudos de Casos e Controles , Feminino , Humanos , Fatores de Risco , SARS-CoV-2
8.
SAR QSAR Environ Res ; 31(1): 49-72, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31766890

RESUMO

In Europe, agencies and official organizations involved in the pesticide control such as the EFSA, ECHA, JRC and ECETOC or even the OECD are pointing out that the software tools based on quantitative structure relationship models, i.e. QSAR and QSPR, have a huge potential to improve the pesticide risk assessment process. In this sense, these non-animal test methods can promote the competitiveness of agriculture in this region: the consumer safety is increased with them due to the possibility of perform an overall better risk assessment of the degradation products and metabolites from pesticides. However, the use of theses computational-based (in silico) tools must be much more systematised and harmonised, improving their validation and including case studies to test them. To open databases, incorporating critical data in an orderly manner for building the models, becomes also necessary. Moreover, quantum chemistry through the Density Functional Theory should be promoted as tool for calculation of quantum descriptors, especially for the study of similar compounds with the same carbon skeleton but differing substitution patterns, e.g. isomers.


Assuntos
Modelos Químicos , Praguicidas/química , Relação Quantitativa Estrutura-Atividade , Medição de Risco/métodos , União Europeia , Modelos Moleculares , Teoria Quântica
9.
Thorax ; 64(6): 496-501, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19237392

RESUMO

BACKGROUND: Although patients admitted to hospital for community-acquired pneumonia (CAP) experience substantial short-term mortality following hospital discharge, few studies have focused on identifying factors that predict mortality after admission to hospital in this population. The objective of this study was to develop and validate a prognostic index for 90-day mortality after hospital discharge among patients with CAP. METHODS: The prognostic index was derived in 1117 adult patients discharged between 2003 and 2007 from a general hospital following admission for CAP. It was validated in 646 consecutive patients with CAP discharged from three other hospitals between 1 November 2005 and 31 July 2006. Risk factors evaluated included host-related factors, severity upon admission, in-hospital management and bacteriology. RESULTS: In the derivation cohort, three factors were independently associated with 90-day mortality: pre-illness functional status, Charlson index (composite measure of co-morbid illnesses) and severity on admission. Mortality at 90 days was 0.7% in the low-risk group, 3.5% in the intermediate-risk group and 17.2% in the high-risk group. In the validation cohort, 90-day mortality in the three groups was 0.6%, 3.9% and 19.6%, respectively. Compared with the low-risk group, the odds ratio for mortality was 43.5 for the high-risk group. The risk categories showed an area under the receiver operating characteristic curve of 0.79 in the derivation cohort and 0.82 in the validation cohort. CONCLUSIONS: The prognostic index accurately stratifies patients admitted to hospital for CAP into low-, intermediate- and high-risk groups for 90-day mortality on discharge. The use of this index could help clinicians improve outcomes in this vulnerable population by targeting specific interventions to each group.


Assuntos
Pneumonia/diagnóstico , Adolescente , Adulto , Fatores Etários , Idoso , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/mortalidade , Métodos Epidemiológicos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Pneumonia/mortalidade , Prognóstico , Espanha/epidemiologia , Adulto Jovem
10.
Clin Transl Oncol ; 10(7): 439-41, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18628074

RESUMO

Hodgkin's disease (HD) is an example of a curable disease. In addition, it can serve as a lesson about other pathologies because of the delayed side effects it produces and the appearance of associated processes that may simulate disease progression. Here we provide a case report of a patient who encapsulates a compendium of situations that may occur in HD.


Assuntos
Doença de Hodgkin/complicações , Doença de Hodgkin/fisiopatologia , Recidiva Local de Neoplasia/fisiopatologia , Infecções Oportunistas/complicações , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criptococose/complicações , Cryptococcus neoformans , Diagnóstico Diferencial , Doença de Hodgkin/terapia , Humanos , Masculino , Recidiva Local de Neoplasia/terapia , Infecções Oportunistas/fisiopatologia , Infecções Pneumocócicas/complicações , Mielofibrose Primária/induzido quimicamente , Streptococcus pneumoniae
11.
Br J Pharmacol ; 152(7): 1012-20, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17906689

RESUMO

BACKGROUND AND PURPOSE: Ototoxicity is a known adverse effect of cisplatin (CDDP). Since apoptosis is involved in the development of some pathological conditions associated with the administration of anticancer drugs, we examined, using immunohistochemical and electrophysiological techniques, the apoptotic changes in the cochlea of Sprague-Dawley (SD) rats after an injection of CDDP (5 mgkg(-1) body weight). EXPERIMENTAL APPROACH: Luciferase assays were used to determine the different caspase activities and ATP levels in protein extracts of whole cochleae. The expression of several apoptotic-related proteins was measured by means of Western blotting. These analyses were performed 2, 7 and 30 days after the CDDP injection. The auditory brain stem response was obtained before and at the different times after the injection of CDDP, before the animals were killed. KEY RESULTS: CDDP significantly increased the levels of caspase-3/7 activity and active caspase-3 protein expression and caspase-3 immunofluorescence staining, caspase-9 activity, and Bax protein expression but decreased Bcl-2 protein expression within the rat cochleae. Threshold shifts were significantly elevated 2 days after CDDP treatment. CONCLUSIONS AND IMPLICATIONS: These findings support the hypothesis that cisplatin-related apoptosis evokes an intrinsic pathway of pro-apoptotic signalling within the rat cochleae. Thus, selective inhibition of the sequence of events involved in the intrinsic apoptotic pathway could provide a strategy to minimize cisplatin-induced ototoxicity.


Assuntos
Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Cisplatino/toxicidade , Cóclea/efeitos dos fármacos , Animais , Antineoplásicos/administração & dosagem , Apoptose/imunologia , Caspase 3/biossíntese , Caspase 3/efeitos dos fármacos , Caspase 3/imunologia , Cisplatino/administração & dosagem , Cóclea/imunologia , Cóclea/patologia , Eletrofisiologia , Ativação Enzimática/efeitos dos fármacos , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Feminino , Imuno-Histoquímica , Injeções Intraperitoneais , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/imunologia
12.
Chemosphere ; 66(7): 1315-22, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16979216

RESUMO

To develop an assay for herbicides in marine environments using microalgae, we have optimized the specie, cell culture media and physical conditions to obtain maximal cellular densities in a 96 well micro format to allow mass assays. We first surveyed several species of 7 unicellular eukaryotic algae genera (Dunaliella, Tetraselmis, Chlorella, Ellipsoidon, Isochrysis, Nannochloropsis, and Phaeodactylum) for vigorous in vitro axenic growth. Once the genus Dunaliella was selected, Dunaliella primolecta was preferred among 9 species (bioculata, minuta, parva, peircei, polymorpha, primolecta, quartolecta, salina and tertiolecta) because it showed the highest growth rates. The components (oligo elements, sugars, amino acids and vitamins) and conditions (light, CO(2), temperature) of the culture media were further optimized to obtain the highest cellular densities (up to 60x10(6)cellsml(-1)) and the shortest cell cycle duration ( approximately 12h) for D. primolecta. Then the toxicity of four representative herbicides, alloxydim, and sethoxydim (inhibitors of acetyl-coA carboxilase), metamitron (inhibitor of photosynthesis) and clopyralid (inhibitor of respiration), were assayed on the optimal culture conditions for D. primolecta during 96h. The results showed that D. primolecta was susceptible to those herbicides in the following order: metamitron > sethoxydim > alloxydim. In contrast, clopyralid did not have any effects. Therefore, D. primolecta microcultures can be used to assay a large number of samples for the presence of herbicides under a saline environment.


Assuntos
Clorófitas/crescimento & desenvolvimento , Monitoramento Ambiental/métodos , Vida Livre de Germes , Herbicidas/toxicidade , Testes de Toxicidade/métodos , Poluentes Químicos da Água/toxicidade , Bioensaio , Clorófitas/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos
13.
J Ethnopharmacol ; 109(1): 48-53, 2007 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-16920301

RESUMO

Tournefortia hartwegiana is a Mexican medicinal plant that is used for the treatment of diabetes, diarrhea and kidney pain. In a previous investigation, the methanolic extract of Tournefortia hartwegiana (METh) showed significant hypoglycemic and anti-diabetic properties on normoglycemic and alloxanized rats. In this context, the purpose of the present study was to establish one of the possible modes of action of METh to induce anti-diabetic activity. METh (310mg/kg) effect on alpha-glucosidase activity was investigated. METh intragastric administration was conducted to determine oral glucose tolerance test (OGTT), using different substrates: glucose, sucrose and maltose. The increase in plasma glucose level was significantly suppressed (P<0.05) by the extract after substrates administration. On the other hand, METh inhibited alpha-glucosidase activity in vitro, in a concentration-dependent manner (IC(50) of 3.16mg/mL). These results suggest that METh might exert its anti-diabetic effect by suppressing carbohydrate absorption from intestine, and thereby reducing the post-prandial increase of blood glucose. On the other hand, the bio-guided fractionation of this extract led to the isolation of: beta-sitosterol (1), stigmasterol (2), lupeol (3), ursolic acid (4), oleanolic acid (5), saccharose (6) and myo-inositol (7), using various chromatographic techniques.


Assuntos
Boraginaceae/química , Inibidores Enzimáticos/farmacologia , Inibidores de Glicosídeo Hidrolases , Hipoglicemiantes/farmacologia , Animais , Glicemia/metabolismo , Cromatografia Gasosa , Cromatografia Gasosa-Espectrometria de Massas , Glucose/farmacologia , Masculino , Maltose/farmacologia , Metanol , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Solventes , Sacarose/farmacologia , Triterpenos/isolamento & purificação
14.
Cancer Res ; 59(13): 3251-6, 1999 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-10397273

RESUMO

Using different molecular techniques, DNA has been detected in the plasma of cancer patients with various types of tumors. We undertook the present study to investigate the presence of plasma DNA, before mastectomy, in patients with breast cancer at diagnosis and to analyze the clinicopathological spectrum of this subgroup of patients with respect to patients without DNA with tumor characteristics. We studied 62 patients with breast cancer, who were selected sequentially after mastectomy and diagnosis of breast carcinomas. Genomic DNA extracted from tumor and normal tissues, normal blood cells, and plasma was used for molecular studies. Alterations in polymorphic markers selected because they had been found to show a high rate of alterations in breast cancer in previous studies (D17S855, D17S654, D16S421, TH2, D10S197, and D9S161), as well as mutations in the p53 gene and aberrant methylation at the first exon of p16INK4a, were used to identify and characterize tumor and plasma DNA. Thirteen clinicopathological parameters were analyzed in each patient. We identified 56 cases (90%) with at least one molecular event in tumor DNA, and 41 cases (66%) with a similar alteration in plasma DNA. Comparison of the clinicopathological parameters between patients with and without plasma DNA revealed significant differences in the axillary involvement, rate of invasive ductal carcinoma, high proliferative index, and the parameter comprised of lymph node metastases, histological grade II, and peritumoral vessel involvement. A high proportion of breast cancer patients exhibited plasma DNA at diagnosis similar to tumor DNA, and its presence correlated significantly with pathological parameters associated with a poor prognosis.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , DNA de Neoplasias/sangue , Genes p53 , Repetições de Microssatélites , Mutação Puntual , Mama/patologia , Neoplasias da Mama/sangue , Neoplasias da Mama/cirurgia , Metilação de DNA , Éxons , Feminino , Marcadores Genéticos , Humanos , Perda de Heterozigosidade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples
15.
Oncogene ; 20(33): 4586-90, 2001 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-11494155

RESUMO

The INK4a/ARF locus encodes two unrelated cell cycle-regulatory proteins that both function in tumor suppression, p16INK4a and p14ARF. In human tumors including breast cancer, alterations affecting selectively p14ARF have been poorly analysed. We have performed a comprehensive analysis of the inactivation mechanisms (mutation, homozygous and hemizygous deletion, and promoter hypermethylation) in a large series of 100 primary breast carcinomas. RT-PCR showed expression variable of the p14ARF transcript, with 17% demonstrating overexpression and 26% demonstrating decreased expression. No detectable alterations were observed in the majority of cases with overexpressed p14ARF mRNA, but 77% of tumors with decreased expression presented at least one of these genetic/epigenetic alterations. Nevertheless, a statistically significant correlation was observed between decreased p14ARF expression and several poor prognostic parameters.


Assuntos
Neoplasias da Mama/genética , Carcinoma/genética , Inibidor p16 de Quinase Dependente de Ciclina/biossíntese , Regulação Neoplásica da Expressão Gênica/genética , Inativação Gênica , Genes p16 , Proteínas de Neoplasias/biossíntese , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Carcinoma/metabolismo , Carcinoma/mortalidade , Metilação de DNA , DNA Complementar/genética , Éxons/genética , Feminino , Humanos , Perda de Heterozigosidade , Proteínas de Neoplasias/genética , Polimorfismo Conformacional de Fita Simples , Prognóstico , Regiões Promotoras Genéticas , RNA Mensageiro/biossíntese , RNA Neoplásico/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Deleção de Sequência
16.
J Clin Oncol ; 16(1): 115-20, 1998 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9440731

RESUMO

PURPOSE: Sporadic nonhereditary breast cancer is recognized as the most common form of this malignancy. Presence of germ-line mutations in the BRCA1 gene of these tumors is an infrequent event. We undertook the present study to evaluate the prevalence of germ-line mutations in patients diagnosed with sporadic breast cancer, and to delimit the clinical spectrum of this subgroup of patients with germ-line mutations and their differences with respect to patients with no evidence of BRCA1 gene mutations. METHODS: We studied 105 patients diagnosed with breast cancer, selected from among our living patients; those with carcinoma-in-situ and those with a definite family history of breast or ovarian cancer were excluded. Genomic DNA, obtained from peripheral-blood lymphocytes, was studied for BRCA1 mutations by polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) and direct DNA sequencing. Fourteen clinicopathologic parameters were analyzed in each patient. RESULTS: Six (5.7%) frameshift mutations that corresponded to truncating proteins and three missense mutations, the functional meaning of which remains speculative, were identified. The patients with germ-line mutations were found to have a more advanced age at diagnosis, as well as a longer median survival (51 months). CONCLUSION: Women with sporadic breast cancer of late onset may display a significant incidence of germline BRCA1 mutations, which occur at a rate not previously determined in this group of patients. The presence of variations in the sequence of the BRCA1 gene could influence the longer survival observed in these patients.


Assuntos
Neoplasias da Mama/genética , Genes BRCA1/genética , Mutação em Linhagem Germinativa/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Família , Feminino , Mutação da Fase de Leitura , Humanos , Pessoa de Meia-Idade , Análise de Sobrevida
17.
Clin Cancer Res ; 7(9): 2821-5, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11555599

RESUMO

PURPOSE: Free plasma RNA has been scarcely studied in patients with cancer. Here we examine the presence of RNA from epithelial tumors in plasma from a series of breast cancer patients and its correlation with tumor characteristics and circulating tumor cells. EXPERIMENTAL DESIGN: beta-actin mRNA was analyzed to check the viability of plasma RNA in samples from 45 patients with breast cancer and 25 controls. Nested primers were used to detect the presence of cytokeratin 19 (CK19) and Mammaglobin in the same samples. Eleven clinicopathological parameters were studied and correlated with molecular parameters. Additionally, we looked for circulating tumor cells in 16 of these patients and in 10 of the controls. RESULTS: All samples showed detectable quantities of beta-actin RNA. In controls, 3 cases (12%) were positive for Mammaglobin, and 5 (20%) were positive for CK19 RNA; of the 45 patients, 27 cases (60%) were positive for Mammaglobin, and 22 (49%) were positive for CK19. These differences were statistically significant (P = 0.001). Tumor size (P = 0.01) and proliferative index (P = 0.02) were associated with the presence of Mammaglobin, CK19, or both RNAs in plasma. Pathological stage (P = 0.06) was close to significance. Although a statistical relationship was not demonstrated, 9 of the 10 patients with circulating tumor cells showed epithelial mRNAs in plasma. CONCLUSIONS: We conclude that epithelial tumor RNA is detectable in plasma from breast cancer patients and that this finding is associated with a probable poor prognosis and circulating tumor cells.


Assuntos
Neoplasias da Mama/patologia , RNA Mensageiro/sangue , Actinas/genética , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Epitélio/metabolismo , Epitélio/patologia , Feminino , Humanos , Queratinas/genética , Mamoglobina A , Proteínas de Neoplasias/genética , Estadiamento de Neoplasias , Células Neoplásicas Circulantes/metabolismo , Prognóstico , RNA Mensageiro/genética , RNA Neoplásico/sangue , RNA Neoplásico/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Uteroglobina/genética
18.
J Ethnopharmacol ; 101(1-3): 37-42, 2005 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-15894444

RESUMO

The purpose of the present investigation was to assess the pharmacological properties of Tournefortia hartwegiana Steud (Boraginaceae), used in traditional medicine for the treatment of diabetes, diarrhea and kidney pain in Morelos, Mexico. Administration of methanol extract from aerial parts of Tournefortia hartwegiana (310 mg/kg body weight/day) for 10 days, to normoglycemic and alloxan-induced diabetic rats, significantly lowered their blood glucose levels (37 and 36%, respectively, p<0.05). The anti-diabetic and hypoglycemic activities due to the MeOH extract were similar to those produced by metformin at 120 mg/kg (positive control, p<0.05). In contrast, the hexane, dichloromethane and MeOH extracts from the same species showed no significant spasmolytic effect and did not have activity in antibacterial and Artemia salina toxicity bioassays.


Assuntos
Boraginaceae , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Fitoterapia , Extratos Vegetais/uso terapêutico , Aloxano , Animais , Masculino , México , Ratos , Ratos Wistar
19.
Arch Bronconeumol ; 41(6): 300-6, 2005 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-15989886

RESUMO

OBJECTIVE: Variability in the management of patients hospitalized with community-acquired pneumonia (CAP) is attributable to many factors. The objective of this study was to determine whether such variability is influenced by the medical specialty area where the patient is treated. PATIENTS AND METHODS: The treatment and outcomes for a random sample of patients with CAP admitted to 4 hospitals over 2 periods (1 year starting March 1, 1998, and 1.5 years starting March 1, 2000) were compared by medical specialty department. Multiple linear and logistic regression models were used to analyze differences. RESULTS: Differences were found between departments in the coverage of atypical pathogens (P<.001). The adjusted mean length of stay in hospital varied between 6.8 and 9.1 days (P<.01), and the duration of intravenous treatment varied between 4.6 and 7.3 days (P<.05). Adjusted models showed that mortality in hospital and at 30 days was significantly higher for patients treated in internal medicine departments (odds ratios, 2.1 and 2, respectively) than for those treated in pulmonology departments. CONCLUSIONS: Interdepartmental differences were observed in how patients hospitalized with CAP were treated and in the outcomes achieved. This variation is probably influenced by the differences that were found in the use of antibiotics.


Assuntos
Antibacterianos/uso terapêutico , Administração de Caso , Infecções Comunitárias Adquiridas/tratamento farmacológico , Medicina , Equipe de Assistência ao Paciente , Pneumonia/tratamento farmacológico , Especialização , Adolescente , Adulto , Idoso , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/classificação , Infecções Comunitárias Adquiridas/complicações , Infecções Comunitárias Adquiridas/epidemiologia , Comorbidade , Quimioterapia Combinada/uso terapêutico , Uso de Medicamentos/estatística & dados numéricos , Feminino , Departamentos Hospitalares , Mortalidade Hospitalar , Hospitalização , Hospitais de Ensino/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pneumonia/complicações , Pneumonia/epidemiologia , Padrões de Prática Médica/estatística & dados numéricos , Estudos Retrospectivos , Choque Séptico/etiologia , Choque Séptico/mortalidade , Espanha/epidemiologia , Resultado do Tratamento
20.
Cancer Lett ; 138(1-2): 209-15, 1999 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-10378795

RESUMO

This study was carried out to evaluate the frequencies of alleles of four polymorphic markers in the 17q21 region in breast cancer patients, and their relation to seven pathological parameters. One hundred and sixty-four patients with breast cancer and 102 controls were analyzed. D17S856, D17S855, D17S1323 and D17S1327 polymorphic markers were studied, and used to investigate loss of heterozygosity in this region. The frequencies of alleles at marker D17S856 differed significantly in breast cancer patients and controls, and were related to histologic features considered to indicate a poor prognosis. When present, the pathophenotype of tumors associated with LOH in the 17q21 region is modified.


Assuntos
Alelos , Neoplasias da Mama/genética , Cromossomos Humanos Par 17 , Perda de Heterozigosidade , Neoplasias da Mama/patologia , Feminino , Genótipo , Humanos
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