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1.
J Phys Chem B ; 127(43): 9356-9365, 2023 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-37871185

RESUMEN

Applying surfactants to reduce the interfacial tension (IFT) on water/oil interfaces is a proven technique. The search for new surfactants and delivery strategies is an ongoing research area with applications in many fields such as drug delivery through nanoemulsions and enhanced oil recovery. Experimentally, the combination of hyperbranched polyglycerol (HPG) with cetyltrimethylammonium bromide (CTAB) substantially reduced the observed IFT of oil/water interface, 0.9 mN/m, while HPG alone was 5.80 mN/m and CTAB alone IFT was 8.08 mN/m. Previous simulations in an aqueous solution showed that HPG is a surfactant carrier. Complementarily, in this work, we performed classical molecular dynamics simulations on combinations of CTAB and HPG with one aliphatic chain to investigate further the interaction of this pair in oil interfaces and propose the mechanism of IFT decrease. Basically, from our results, one can observe that the IFT reduction comes from a combination of effects that have not been observed for other dual systems: (i) Due to the CTAB-HPG strong interaction, a weakening of their specific and isolated interactions with the water and oil phases occurs. (ii) Aggregates enlarge the interfacial area, turning it into a less ordered interface. (iii) The spread of individual molecules charge profiles leads to the much lower interfacial tension observed with the CTAB+HPG systems.

2.
Clin Microbiol Infect ; 28(6): 881.e7-881.e12, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35026376

RESUMEN

OBJECTIVE: To assess the influence of the emergence of severe acute respiratory syndrome coronavirus 2 and the implementation of public health measures on the seasonality of outpatient antibiotic use and their possible association with the incidence of influenza. METHODS: We performed a time-series ecological study in 1516 primary care centres of Andalusia, Spain, comparing the coronavirus disease 2019 period (April 2020 to March 2021) with the 6 previous years. We assessed the number of packs and defined daily doses per 1000 inhabitants of antibacterials and key antibiotics commonly used for acute respiratory tract infections and the number of influenza-positive cases per 100 000 inhabitants. We calculated the correlation between variables and analyzed the seasonal patterns and differences in quarterly antibiotic use. RESULTS: For all quarters, a significant correlation was observed between influenza activity and antibiotic use (Spearman's r = 0.94; p < 0.001). Before the pandemic period, both variables presented similar seasonal patterns. After the start of the pandemic, influenza activity was suppressed and the pattern of antibiotic use flattened into a straight line (R2 = 0.96; p = 0.022) with a quarterly change of 3.9% (p = 0.007). Total antibiotic use and antibiotics used for treating acute respiratory tract infections showed significant reductions in all quarters compared to the previous year (p < 0.01). DISCUSSION: The coronavirus disease 2019 pandemic has strongly influenced the seasonality of antibiotic use in primary care. The decline in respiratory viruses, among which the influenza virus is a major player that may act as a proxy for general prevalence, is proposed as a reason for the flattening of the seasonal fluctuations of outpatient antibiotic use in our region.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , COVID-19 , Gripe Humana , Infecciones del Sistema Respiratorio , Antibacterianos/uso terapéutico , COVID-19/epidemiología , Humanos , Gripe Humana/tratamiento farmacológico , Gripe Humana/epidemiología , Pacientes Ambulatorios , Pandemias , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/epidemiología , Estaciones del Año
3.
Polymers (Basel) ; 14(9)2022 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-35566871

RESUMEN

The influence of processing intumescent bio-based poly(lactic acid) (PLA) composites by injection and fused filament fabrication (FFF) was evaluated. A raw (ANa) and two acidic-activated (AH2 and AH5) montmorillonites were added to the intumescent formulation, composed by lignin and ammonium polyphosphate, in order to evaluate the influence of the strength and the nature (Brønsted or Lewis) of their acidic sites on the fire behavior of the composites. The thermal stability and the volatile thermal degradation products of the composites were assessed. The injected and 3D-printed composites were submitted to cone calorimeter (CC), limit oxygen index (LOI), and UL-94 flammability tests. A similar tendency was observed for the injected and 3D-printed samples. The high density of strong Lewis sites in AH2 showed to be detrimental to the fire-retarding properties. For the CC test, the addition of the intumescent composite reduced the peak of heat released (pHRR) in approximately 49% when compared to neat PLA, while the composites containing ANa and AH5 presented a reduction of at least 54%. However, the addition of AH2 caused a pHRR reduction of around 47%, close to the one of the composite without clay (49%). In the LOI tests, the composites containing ANa and AH5 achieved the best results: 39% and 35%, respectively, for the injected samples, and 35 and 38% for the 3D-printed samples. For the composite containing AH2 the LOI values were 34% and 32% for injected and 3D-printed samples, respectively. Overall, the best performance in the flammability tests was achieved by the composites containing clays with only weak and moderate strength acidic sites (ANa and AH5).

4.
Polymers (Basel) ; 12(12)2020 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-33255516

RESUMEN

A raw montmorillonite (Mt) was submitted to different acidic activation times in order to investigate the influence of the strength and the nature (Brønsted and Lewis) of acidic sites on the synergistic action with an intumescent formulation (IF) composed of ammonium polyphosphate (APP) and pentaerythritol (PER) when incorporated into a polypropylene (PP) matrix. The acidity of the Mt samples was quantified by ammonia temperature-programmed desorption (TPD-NH3) and Fourier transform infrared spectroscopy (FTIR) with pyridine adsorption. The mineral clays were also characterized by X-ray fluorescence (XRF), X-ray diffraction (XRD), nitrogen adsorption analysis and particle size distribution. Thermogravimetric analysis (TGA), limit oxygen index (LOI) and UL-94 were performed to evaluate the flame-retardant properties and the thermal stability. The TGA results show that the final residue increased 2 to 3 fold in comparison to the values predicted theoretically. The flammability properties achieved a maximum for the system containing an excess of moderate-strength Brønsted sites relative to the Lewis ones, reaching 38% in the LOI test. This result suggests that the presence of these Brønsted acidic sites is important, as they take part in the esterification reaction between APP and PER which gives rise to the char formation. The FTIR-Pyr adsorption and flammability results indicate that both the nature and strength of the acidic sites influence the flame-retardant properties.

5.
PLoS One ; 15(5): e0233062, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32413054

RESUMEN

BACKGROUND: Most effective strategies designed to improve antimicrobial prescribing have multiple approaches. We assessed the impact of the implementation of a rigorous antimicrobial guide and subsequent multifaceted interventions aimed at improving antimicrobial use in Primary Care. METHODS: A quasi-experimental study was designed. Interventions aimed at achieving a good implementation of the guide consisted of the development of electronic decision support tools, local training meetings, regional workshops, conferences, targets for rates of antibiotic prescribing linked to financial incentives, feedback on antibiotic prescribing, and the implementation of a structured educational antimicrobial stewardship program. Interventions started in 2011, and continued until 2018. Outcomes: rates of antibiotics use, calculated into defined daily doses per 1,000 inhabitants-day (DID). An interrupted time-series analysis was conducted. The study ran from January 2004 until December 2018. RESULTS: Overall annual antibiotic prescribing rates showed increasing trends in the pre-intervention period. Interventions were followed by significant changes on trends with a decline over time in antibiotic prescribing. Overall antibiotic rates dropped by 28% in the Aljarafe Area and 22% in Andalusia between 2011 and 2018, at rates of -0.90 DID per year (95%CI:-1.05 to -0.75) in Aljarafe, and -0.78 DID (95%CI:-0.95 to -0.60) in Andalusia. Reductions occurred at the expense of the strong decline of penicillins use (33% in Aljarafe, 25% in Andalusia), and more precisely, amoxicillin clavulanate, whose prescription plummeted by around 50%. Quinolones rates decreased before interventions, and continued to decline following interventions with more pronounced downward trends. Decreasing cephalosporins trends continued to decline, at a lesser extent, following interventions in Andalusia. Trends of macrolides rates went from a downward trend to an upward trend from 2011 to 2018. CONCLUSIONS: Multifaceted interventions following the delivering of a rigorous antimicrobial guide, maintained in long-term, with strong institutional support, could led to sustained reductions in antibiotic prescribing in Primary Care.


Asunto(s)
Antibacterianos/uso terapéutico , Programas de Optimización del Uso de los Antimicrobianos/tendencias , Pautas de la Práctica en Medicina/tendencias , Atención Primaria de Salud/tendencias , Programas de Optimización del Uso de los Antimicrobianos/estadística & datos numéricos , Técnicas de Apoyo para la Decisión , Utilización de Medicamentos/estadística & datos numéricos , Utilización de Medicamentos/tendencias , Humanos , Prescripción Inadecuada/prevención & control , Prescripción Inadecuada/estadística & datos numéricos , Prescripción Inadecuada/tendencias , Análisis de Series de Tiempo Interrumpido , Pautas de la Práctica en Medicina/estadística & datos numéricos , Atención Primaria de Salud/estadística & datos numéricos , España
6.
Clin Chem ; 55(10): 1834-42, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19661141

RESUMEN

BACKGROUND: Tissue factor (TF), the main initiator of blood coagulation, is also a signaling protein that regulates cancer progression. TF synthesis was recently shown to be affected by tumor suppressor genes (TSGs) in tumor cell lines. We therefore studied TF gene (F3) expression and the status of genes coding for tumor protein p53 (TP53), phosphatase and tensin homolog (PTEN), and serine/threonine kinase 11 (STK11) in non-small cell lung cancer (NSCLC). Heparanase (HPSE) gene expression was also measured because this endo-beta-D-glucuronidase was recently shown to enhance TF gene expression. METHODS: TF and heparanase mRNA expression was measured by real-time PCR in 53 NSCLC tumors. Exons 5-8 of TP53 were sequenced from genomic DNA. Mutations of PTEN and STK11 were screened by multiplex ligation-dependent probe amplification. RESULTS: TF mRNA levels were significantly higher in T(3)-T(4) tumors (P = 0.04) and in stages III-IV of NSCLC (P = 0.03). Mutations of TP53, STK11, and PTEN were identified in 20 (37.7%), 21 (39%), and 20 (37.7%) of tumors, respectively. TF expression was higher in mutated TP53 (TP53(Mut)) (P = 0.02) and PTEN(Mut) (P = 0.03) samples. Moreover, TF mRNA increased from 2700 copies (no mutation) to 11 6415 when 3 TSG were mutated. Heparanase gene expression did not differ according to TF gene (F3) expression or TSG mutation. The median survival time was shorter in patients with tumor TF mRNA levels above median values (relative risk 2.2; P = 0.03, multivariate analysis) and when TP53 was mutated (relative risk 1.8; P = 0.02). CONCLUSIONS: These results provide clear evidence that combined oncogene events affecting TSG dramatically increase TF gene expression in lung tumors. Moreover, this study suggests that TF gene expression could be used as a prognostic marker in NSCLC.


Asunto(s)
Biomarcadores de Tumor/biosíntesis , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , Fosfohidrolasa PTEN/genética , Tromboplastina/biosíntesis , Proteína p53 Supresora de Tumor/genética , Quinasas de la Proteína-Quinasa Activada por el AMP , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Glucuronidasa/biosíntesis , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Mutación , Reacción en Cadena de la Polimerasa , Modelos de Riesgos Proporcionales , Proteínas Serina-Treonina Quinasas/biosíntesis , Tasa de Supervivencia
7.
Curr Opin Pulm Med ; 14(5): 397-402, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18664968

RESUMEN

PURPOSE OF REVIEW: This review addresses the clinical and biological strategy to be applied for the diagnosis of heparin-induced thrombocytopenia. RECENT FINDINGS: Heparin-induced thrombocytopenia is a severe prothrombotic disease caused by immunoglobulin G antibodies, which bind to platelet factor 4 and activate platelets with subsequent increased thrombin generation. Venous and arterial thromboses are frequent, explaining why substituting heparin with a potent alternative anticoagulant (danaparoid, lepirudin, or argatroban) is necessary in every affected patient. However, the diagnosis of heparin-induced thrombocytopenia is often difficult and it has to be diagnosed on the basis of clinical criteria and reliable laboratory tests (immunoassays and platelet activation tests). The profiles of platelet count evolution suggestive of heparin-induced thrombocytopenia in cardiac surgery patients are now well defined. For other clinical settings, the usefulness of a scoring system, the '4Ts', estimating the probability of heparin-induced thrombocytopenia before laboratory testing, combined with one immunoassay allowing specific detection of heparin-induced thrombocytopenia antibodies, has been recently documented. SUMMARY: Recent studies have demonstrated the usefulness of combining a pretest clinical score (4Ts) and biological assays to diagnose heparin-induced thrombocytopenia and the algorithms that have to be applied for clinical practice are now better defined.


Asunto(s)
Heparina/efectos adversos , Trombocitopenia/diagnóstico , Trombocitopenia/inmunología , Algoritmos , Anticuerpos/inmunología , Heparina/inmunología , Humanos , Inmunoensayo , Inmunoglobulina G/inmunología , Factor Plaquetario 4/inmunología , Trombocitopenia/inducido químicamente
8.
J Med Case Rep ; 12(1): 199, 2018 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-29966534

RESUMEN

BACKGROUND: Diabetes and myelodysplastic syndrome are two conditions that may coexist in a single patient, since both diseases are prevalent in the elderly. The pathophysiology of myelodysplastic syndrome involves recurrent genetic mutations, especially in genes controlling epigenetic regulation. Although the pathophysiology of diabetes is not well understood, several studies suggest a role of epigenetics in type 2 diabetes. CASE PRESENTATION: We report here for the first time the case of a 75-year-old Caucasian man who was treated for both diabetes and acute myeloid leukemia secondary to myelodysplastic syndrome, with a temporal association between glycemic dysregulation and the intake of 5-azacitidine. In fact, 2-3 days after starting each 7-day cycle of 5-azacitidine, he reported higher blood glucose levels, requiring an increased dose of self-administered insulin. CONCLUSION: This observation could help to understand the pathophysiology of these two conditions and could encourage physicians to monitor blood glucose levels in patients under hypomethylating agent with a history of diabetes.


Asunto(s)
Antimetabolitos Antineoplásicos/efectos adversos , Azacitidina/efectos adversos , Diabetes Mellitus Tipo 2/metabolismo , Glucosa/metabolismo , Leucemia Mieloide Aguda/tratamiento farmacológico , Síndromes Mielodisplásicos/tratamiento farmacológico , Anciano , Antimetabolitos Antineoplásicos/uso terapéutico , Azacitidina/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatología , Epigénesis Genética , Humanos , Leucemia Mieloide Aguda/etiología , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/fisiopatología , Masculino , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/fisiopatología
9.
Lung Cancer ; 56(2): 273-80, 2007 May.
Artículo en Inglés | MEDLINE | ID: mdl-17208328

RESUMEN

Matrix metalloproteinases (MMP) including MMP-2 and MMP-9 play a major role in tumour invasion by proteolysing the extracellular matrix. Their activation, particularly that of MMP-9, is partly dependent on plasmin that is inhibited by TFPI-2 (tissue factor pathway inhibitor-2), a serine protease inhibitor whose gene expression is decreased in about one-third of non-small cell lung cancers (NSCLC). In addition, MMP-2 and MMP-9 are essential in the development of NSCLC and can be regulated by functional promoter polymorphisms. In this study, the -1306C/T MMP-2, -735C/T MMP-2 and -1562C/T MMP-9 polymorphisms were analysed in 90 NSCLC patients and 90 controls. In addition, the promoter region of the TFPI-2 gene was screened for sequence variations in both groups by DHPLC. A -167G/A polymorphism was identified in 3% of controls whereas none of the 90 patients exhibited this genetic variation in the TFPI-2 promoter region. Moreover, no difference in -1306C/T MMP-2, -735C/T MMP-2 and -1562C/T MMP-9 genotypes was found between cases and controls. However, the homozygous -1562CC MMP-9 genotype was more frequent in patients with squamous cell carcinoma than in controls (p=0.018). When genotype distributions were compared to MMP-2 and MMP-9 gene expression in tumours, no relationship was found with the -1306 MMP-2 and -1562 MMP-9 polymorphisms. In contrast, tumour MMP-2 gene expression was lower in homozygous -735CC patients than in those with CT or TT genotypes. In addition, the survival time was longer in patients with the MMP-2 -735T allele than in those with the CC genotype (p=0.02). The relative risk of death was increased 2.6-fold in -735CC patients (p=0.045; 95% CI=1.0-6.7). The results of this study suggest that the -735C/T MMP-2 polymorphism might be an independent prognostic marker in NSCLC, but this should be confirmed in a larger cohort of patients.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genética , Polimorfismo Genético , Anciano , Carcinoma de Pulmón de Células no Pequeñas/enzimología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Cartilla de ADN , Femenino , Expresión Génica , Genotipo , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Regiones Promotoras Genéticas , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
10.
Thromb Res ; 121(3): 333-8, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17568659

RESUMEN

INTRODUCTION: Fibrinogen Aalpha-Thr312Ala and Factor XIII Val34Leu polymorphisms have been shown to modify fibrin clot structure and function. However, clinical studies have yielded conflicting results on their possible association with venous thromboembolism (VTE). METHODS: We studied the association between these two polymorphisms and VTE in a hospital-based case-control study. We also assessed whether an independent or interactive association exists between Aalpha-fibrinogen Thr312Ala and FXIII Val34Leu polymorphisms and VTE. Fibrinogen Aalpha-Thr312Ala and FXIII Val34Leu polymorphisms were determined after PCR and restriction endonuclease digestion in 286 patients with idiopathic VTE and 286 age- and gender-matched controls. Results were analysed using a conditional logistic regression model for matched series. RESULTS: The Fg-Aalpha 312Ala allele was associated with higher risk of VTE (OR 1.5; 95% CI: 1.1 to 2.2, p=0.01) while the FXIII 34Leu allele appeared protective (OR 0.7; 95% CI: 0.6 to 0.9, p=0.02). Both alleles demonstrated an independent association with idiopathic VTE after adjustment for Factor V Leiden and G20210A prothrombin polymorphisms. There was no interaction between the fibrinogen Aalpha-Thr312Ala and FXIII Val34Leu polymorphisms for the risk of VTE. CONCLUSION: In this case-control study, the fibrinogen Fg-Aalpha 312Ala allele was associated with an increased risk of VTE. The FXIII 34Leu allele was also significantly associated with a lower risk of VTE without any interaction between the two polymorphisms studied.


Asunto(s)
Factor XIIIa/genética , Fibrinógeno/genética , Polimorfismo Genético , Tromboembolia Venosa/sangre , Tromboembolia Venosa/genética , Anciano , Anciano de 80 o más Años , Alelos , Sustitución de Aminoácidos , Estudios de Casos y Controles , Factor V/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación Puntual , Embolia Pulmonar/sangre , Embolia Pulmonar/genética , Factores de Riesgo
11.
Hum Mutat ; 27(6): 600, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16705712

RESUMEN

Antithrombin (AT) is a major physiological inhibitor of hemostasis. We report 22 novel antithrombin gene (SERPINC1) mutations associated with antithrombin deficiency in 17 French and five German families. They were all present at the heterozygous state. Nine missense mutations accounted for type I deficiency, defined by equally low antithrombin activity and antigen level. Most of them (7/9) affected highly conserved serpin residues and were associated with venous thrombosis occurring at a young age (before age 32). One splice site, one nonsense mutation, three small deletions and one insertion were also identified as a cause for type I antithrombin deficiency. Seven other missense mutations were identified in type II or unclassified AT deficiency; g.5270C>T (p.T147I, T115I) and g.5281A>T (p.I151F, I119F) change residues in the heparin binding region, g.13267C>G (p.P439A, P407A) and g.13271T>C (p.F440S, F408S) affect amino acids in the pleiotropic region, g.2372G>A (p.G25D, G-8D) changes a signal peptide amino acid, g.2456G>C (p.C53S, C21S) affects one of the three disulfide bonds of the protein, and g.7585A>T (p.M347K, M315K) changes a nonconserved residue on strand 2C.


Asunto(s)
Deficiencia de Antitrombina III/genética , Antitrombina III/genética , Mutación , Antitrombina III/química , Deficiencia de Antitrombina III/clasificación , Deficiencia de Antitrombina III/diagnóstico , Análisis Mutacional de ADN , Femenino , Francia , Alemania , Heterocigoto , Humanos , Fenotipo , Factores de Riesgo
12.
Rev Prat ; 56(7): 710-8, 2006 Apr 15.
Artículo en Francés | MEDLINE | ID: mdl-16739902

RESUMEN

Heparin-induced thrombocytopenia (HIT) is due to IgG antibodies specific to platelet factor 4. HIT is characterized by a delayed decrease in platelet count (after the 5th day of treatment) often associated with thromboses. The presence of heparin-dependent antibodies has to be demonstrated to confirm HIT by ELISA or platelet activation tests. Withdrawal of heparin is always necessary, as well as the administration of an alternative antithrombotic agent. Danaparoid sodium or lepirudin are both recommended but associated with a significant risk of bleeding in case of renal failure. Oral anticoagulants can only be given when platelet count is corrected and if the clinical evolution is favorable. Early administration of coumadin for the treatment of venous thromboembolic disease efficiently prevents HIT, which could disappear in the future with the wider use of new antithrombotic agents such as fondaparinux or direct anti-thrombin agents.


Asunto(s)
Anticoagulantes/efectos adversos , Heparina/efectos adversos , Trombocitopenia/inducido químicamente , Trombocitopenia/fisiopatología , Formación de Anticuerpos , Anticoagulantes/inmunología , Ensayo de Inmunoadsorción Enzimática , Heparina/inmunología , Humanos , Inmunoglobulina G/inmunología , Trombocitopenia/diagnóstico , Trombocitopenia/terapia
13.
Retin Cases Brief Rep ; 10(3): 239-43, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26771860

RESUMEN

PURPOSE: To report a case of chorioretinopathy, which preceded diagnosis of Hodgkin's lymphoma. METHODS: Single patient case report. RESULTS: A 61-year-old woman with a history of breast cancer in remission and low-grade follicular lymphoma without criteria of high tumor burden presented with bilateral multifocal chorioretinopathy. The usual etiologies of chorioretinopathy were excluded, and subsequent onset of fever and back pain revealed the diagnosis of Hodgkin's lymphoma. The evolution of this case of ocular involvement was concordant with that of Hodgkin's lymphoma. CONCLUSION: The authors describe a case of Hodgkin's lymphoma postdating the onset of chorioretinopathy, emphasizing the need to research an underlying disorder when faced with any inflammatory intraocular disease, and the role of indocyanine green angiography in the diagnosis and follow-up of posterior uveitis.


Asunto(s)
Enfermedades de la Coroides/etiología , Enfermedad de Hodgkin/complicaciones , Enfermedades de la Coroides/diagnóstico , Femenino , Enfermedad de Hodgkin/diagnóstico , Humanos , Persona de Mediana Edad , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/etiología , Uveítis/diagnóstico
15.
Thromb Haemost ; 94(1): 101-6, 2005 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16113792

RESUMEN

Retinal vein occlusion (RVO) is a multifactorial disease involving vessel damage, stasis, viscosity and thrombosis. Conflicting findings on hereditary thrombophilic risk factors have been reported and their impact on RVO features remains to be defined. The aim of the present study was to evaluate the prevalence of hereditary thrombophilic risk factors (HTRF) and characteristics of RVO in patients with or without HTRF. The design of the study was a prospective, observational case series. Two hundred and thirty-four patients with RVO were included consecutively. A French healthy population of the same region was studied as control group. The HTRF studied were protein C (PC), protein S (PS) and antithrombin (AT) deficiencies, factor V Leiden (FVL) and factor II 20210A polymorphisms. Chi-Square was used for comparison with the healthy subjects and between RVO patient with and without HTRF according to localisation (branch vs. central), type of RVO (ischemic or non-ischemic), recurrence, age at first event and classical vascular risk factors. Twenty-two patients had HTRF (12 FV Leiden heterozygotes, 9 FII 20210A heterozygotes and 1 PS deficiency). No AT or PC deficiency was detected. Frequencies of PS deficiency, FVL and FII 20210A allele were similar to the reference population as well as to published data in the general caucasian population. Eighty-six patients experienced their first episode before the age of 60 years. Systemic hypertension, glaucoma and angina were significantly less frequent in patients with RVO before 60 years. Fourteen of the 22 patients with one HTRF (64%) experienced their first episode of RVO before the age of 60 years compared to 72 of 212 without HTRF (34%) (p = 0.006). Heterozygote status for FV Leiden was significantly more frequent in patients who had experienced their first episode of RVO before 60 years (p = 0.027). In conclusion, this study suggests a role of FV Leiden in the occurrence of RVO in patients younger than 60 years who exhibit fewer acquired vascular risk factors than in older patients.


Asunto(s)
Factor V/genética , Oclusión de la Vena Retiniana/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Antitrombinas/biosíntesis , Factor V/biosíntesis , Femenino , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Proteína C/biosíntesis , Proteína S/biosíntesis , Protrombina/biosíntesis , Oclusión de la Vena Retiniana/epidemiología , Factores de Riesgo , Trombofilia/epidemiología , Trombofilia/genética , Trombosis , Factores de Tiempo
16.
Blood Coagul Fibrinolysis ; 14(1): 83-5, 2003 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-12544734

RESUMEN

A nucleotide 807T variant of the glycoprotein Ia gene that correlates with increased platelet surface levels of the platelet collagen receptor alpha2beta1 was recently found to be associated with an increased risk of ischaemic stroke in younger patients. We report the history of twins who developed ischaemic strokes and were shown to be homozygous for the alpha2 807T allele. The twins developed ischaemic strokes at the ages of 23 and 33 years, one of them with recurrent events. They had no conventional risk factors. Cardiac and vascular investigations were normal and no aetiology could be found. There was a family history of cerebrovascular disease. Genotyping of glycoprotein alpha2 C807 T was performed and both twins were found to be homozygous for the 807T allele. This allele probably contributed to the occurrence of strokes in these young men. Further prospective studies are needed to evaluate whether screening for this polymorphism should be considered in young patients with unexplained stroke, particularly when a positive family history was found.


Asunto(s)
Enfermedades en Gemelos/genética , Integrina alfa2beta1/genética , Polimorfismo de Nucleótido Simple , Accidente Cerebrovascular/genética , Adulto , Alelos , Plaquetas/química , Salud de la Familia , Genotipo , Homocigoto , Humanos , Integrina alfa2beta1/fisiología , Masculino , Gemelos Monocigóticos
17.
Thromb Haemost ; 103(1): 145-50, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20062918

RESUMEN

The diagnosis of heparin-induced thrombocytopenia (HIT) is based on clinical criteria and biological assays. Most immunoassays detect antibodies (either IgG alone or additionally IgA and IgM) against PF4 immobilised in wells of microtiter plates with stoichiometric concentrations of polyanion (heparin or polyvinylsulfonate). We studied whether diagnostic sensitivity and/or specificity for HIT could be improved using a novel assay in which unfractionated heparin is immobilised alone to the microwells, with PF4 (and, potentially, other heparin-dependent antigen proteins) provided by adding platelet lysate during the procedure. Samples from 101 patients with suspected HIT and from 101 controls (including 50 with antiphospholipid antibodies) were tested. The global assay (Zymutest HIA IgG/A/M, Hyphen BioMed) was positive for 39 of 40 patients with definite HIT (positive PF4-specific ELISA and positive serotonin release assay). It was positive in only two of the 101 control patients studied and also in 14 of the 61 patients with suspected HIT for whom the disease was excluded (specificity (sp): 77%). On the other hand, Zymutest HIA IgG, an IgG-specific assay, was positive in only six patients without HIT (Sp: 90%). Heparin-dependent IgG antibodies were present at higher levels in patients with definite HIT than in those for whom the diagnosis of HIT was ruled out. A single ELISA that detects IgG antibodies is more effective for the diagnosis of HIT in clinical practice. These results also support the hypothesis that heparin-dependent antibodies of IgG class have a major role in the pathogenesis of HIT.


Asunto(s)
Anticoagulantes/efectos adversos , Ensayo de Inmunoadsorción Enzimática , Heparina/efectos adversos , Inmunoglobulina G/sangre , Factor Plaquetario 4/inmunología , Trombocitopenia/diagnóstico , Anticoagulantes/inmunología , Estudios de Casos y Controles , Femenino , Heparina/inmunología , Humanos , Masculino , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Trombocitopenia/inducido químicamente , Trombocitopenia/inmunología
18.
J Interv Card Electrophysiol ; 28(2): 101-7, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20454840

RESUMEN

PURPOSE: Ischemic stroke is a frequent pathology with high rate of recurrence and significant morbidity and mortality. There are several causes of stroke, affecting prognosis, outcomes, and management, but in many cases, the etiology remains undetermined. We hypothesized that atrial fibrillation was involved in this pathology but underdiagnosed by standard methods. The aim of the study was to determine the incidence of atrial fibrillation in cryptogenic ischemic stroke by using continuous monitoring of the heart rate over several months. The secondary objective was to test the value of atrial vulnerability assessment in predicting spontaneous atrial fibrillation. METHODS AND RESULTS: We prospectively enrolled 24 patients under 75 years of age, 15 men and 9 women of mean age 49 years, who within the last 4 months had experienced cryptogenic stroke diagnosed by clinical presentation and brain imaging and presumed to be of cardioembolic mechanism. All causes of stroke were excluded by normal 12-lead ECG, 24-h Holter monitoring, echocardiography, cervical Doppler, hematological, and inflammatory tests. All patients underwent electrophysiological study. Of the patients, 37.5% had latent atrial vulnerability, and 33.3% had inducible sustained arrhythmia. Patients were secondarily implanted with an implantable loop recorder to look for spontaneous atrial fibrillation over a mean follow-up interval of 14.5 months. No sustained arrhythmia was found. Only one patient had non-significant episodes of atrial fibrillation. CONCLUSION: In this study, symptomatic atrial fibrillation or AF with fast ventricular rate has not been demonstrated by the implantable loop recorder in patients under 75 years with unexplained cerebral ischemia. The use of this device should not be generalized in the systematic evaluation of these patients. In addition, this study attests that the assessment of atrial vulnerability is poor at predicting spontaneous arrhythmia in such patients.


Asunto(s)
Fibrilación Atrial/complicaciones , Fibrilación Atrial/epidemiología , Isquemia Encefálica/epidemiología , Isquemia Encefálica/etiología , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Ecocardiografía , Electrocardiografía/métodos , Electrocardiografía Ambulatoria , Técnicas Electrofisiológicas Cardíacas , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prevalencia , Ultrasonografía Doppler
19.
PLoS One ; 4(1): e4158, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19129913

RESUMEN

BACKGROUND: ID2 is a member of a subclass of transcription regulators belonging to the general bHLH (basic-helix-loop-helix) family of transcription factors. In normal cells, ID2 is responsible for regulating the balance between proliferation and differentiation. More recent studies have demonstrated that ID2 is involved in tumor progression in several cancer types such as prostate or breast. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we investigated, for the first time, the relationship between the expression of ID2 in non-small cell lung cancer (NSCLC) patients and the clinicopathological features and prognosis of these patients. Immunohistochemistry was performed on tissue microarrays, which included 62 NSCLC tumors. In malignant tissues, ID2 expression has been detected in both the nuclear and cytoplasmic compartments, but we have demonstrated that only nuclear expression of ID2 is inversely correlated with the differentiation grade of the tumor (p = 0.007). Interestingly, among patients with poorly differentiated tumors, high nuclear expression of ID2 was an independent and unfavorable prognostic factor for survival (p = 0.036). CONCLUSIONS: These results suggest that ID2 could be involved in tumor dedifferentiation processes of NSCLC, and could be used as prognostic marker for patients with poorly differentiated tumors.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Proteína 2 Inhibidora de la Diferenciación/análisis , Proteína 2 Inhibidora de la Diferenciación/metabolismo , Neoplasias Pulmonares/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Diferenciación Celular , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/patología , Estudios Prospectivos , Análisis por Matrices de Proteínas , Células Tumorales Cultivadas
20.
J Thorac Oncol ; 3(7): 689-97, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18594312

RESUMEN

INTRODUCTION: Tissue factor (TF) is the physiological trigger of blood coagulation, but it could also have an important role in cancer by regulating VEGF expression and angiogenesis. METHODS: TF expression was studied by real-time PCR in lung tumors of 64 patients with non-small-cell lung cancer (NSCLC) and by immunohistochemical analysis. The gene expression of two VEGF isoforms, VEGF165 and VEGF189, was also evaluated. Microvascular density (MVD) was studied by measuring Von Willebrand Factor (VWF) mRNA levels and by immunohistochemistry using an anti-CD34 antibody. RESULTS: TF mRNA levels were significantly lower than in corresponding non-affected lung tissues. However, TF expression was higher in T3-T4 tumors and this result was confirmed by immunohistochemistry. VEGF189 mRNA levels were ten times higher than those of VEGF165 and well correlated with TF mRNA levels. MVD was lower in the inner part of tumors than in the adjacent non-affected lung without being related to TF expression. Finally, codon 12 K-ras mutation was found in 8 lung carcinomas, and higher TF and VEGF189 mRNA levels were measured in mutated tissues (p < 0.001). CONCLUSION: These results suggest that high TF expression in lung tumors may result from K-ras mutation and contribute to NSCLC progression, probably via mechanisms other than angiogenesis.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Genes ras/genética , Neoplasias Pulmonares/metabolismo , Mutación , Neovascularización Patológica , Tromboplastina/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/irrigación sanguínea , Carcinoma de Pulmón de Células no Pequeñas/genética , Línea Celular Tumoral , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/irrigación sanguínea , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tromboplastina/genética , Factor A de Crecimiento Endotelial Vascular/genética , Factor de von Willebrand/metabolismo
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