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2.
Sci Rep ; 10(1): 20175, 2020 11 19.
Artículo en Inglés | MEDLINE | ID: mdl-33214636

RESUMEN

No systemic biomarker of Central Serous Chorioretinopathy (CSCR) has been identified. Lipocalin 2 (LCN2 or NGAL), alone or complexed with MMP-9 (NGAL/MMP-9), is increased in several retinal disorders. Serum levels of LCN2 and NGAL/MMP-9 were measured in CSCR patients (n = 147) with chronic (n = 76) or acute/recurrent disease (n = 71) and in age- and sex-matched healthy controls (n = 130). Samples with CRP > 5 mg/L, creatinine > 100 µmol/L, and/or urea > 7.5 mmol/L were excluded. Serum LCN2 was lower in CSCR patients than controls (81.4 ± 48.7 vs 107.3 ± 44.5 ng/ml, p < 0.0001), and lower in acute/recurrent CSCR than controls (p < 0.001) and chronic CSCR (p = 0.006). Serum NGAL/MMP-9 was lower in CSCR patients than controls (47.2 ± 40.7 vs 74.1 ± 42.6, p < 0.0001), and lower in acute/recurrent CSCR than controls (p < 0.001) and chronic CSCR (p = 0.002). A ROC curve showed that for LCN2 serum levels, the 80-ng/ml cutoff value allows to discriminate acute/recurrent CSCR from controls with 80.3% sensitivity and 75.8% specificity, and for NGAL/MMP-9 serum levels, a 38-ng/ml cutoff value allows to discriminate acute/recurrent CSCR from controls with 69.6% sensitivity and 80.3% specificity. In both acute and chronic CSCR, low serum LCN2 and NGAL/MMP-9, provide a biological link between the two CSCR forms, and potential susceptibility to oxidative stress and innate immune dysregulation in CSCR.


Asunto(s)
Biomarcadores/sangre , Coriorretinopatía Serosa Central/sangre , Lipocalina 2/sangre , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Metaloproteinasa 9 de la Matriz/sangre , Persona de Mediana Edad , Curva ROC , Estudios Retrospectivos
3.
Clin Immunol ; 197: 54-59, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30125675

RESUMEN

OBJECTIVE: To describe the outcome and tolerance in patients treated with anti-TNFα in severe and refractory major vessel disease in Behçet's disease (BD). METHODS: A multicenter study evaluating 18 refractory BD patients with major vessel involvement [pulmonary artery (n = 4), aorta (n = 4) or peripheral artery aneurysm (n = 1) and/or pulmonary artery (n = 7), inferior vena cava (n = 5), or intra-cardiac (n = 3) thrombosis or Budd Chiari Syndrome (n = 2)] treated with anti-TNFα agents. RESULTS: Vascular remission was achieved in 16 (89%) patients. The 9 months risk of relapse was significantly higher with conventional immunosuppressants used prior anti-TNFα agents as compared to anti-TNFα therapy [OR = 8.7 (1.42-62.6), p = 0.03]. The median daily dose of corticosteroids significantly decreased at 12 months. Side effects included infection (n = 4) and pulmonary edema (n = 1). CONCLUSION: TNFα-antagonists are safe and might be associated with a decreased risk of relapse at 9 months compared to conventional immunosuppressants in BD patients with major vessels disease.


Asunto(s)
Adalimumab/uso terapéutico , Antirreumáticos/uso terapéutico , Síndrome de Behçet/tratamiento farmacológico , Infliximab/uso terapéutico , Trombosis/fisiopatología , Adulto , Enfermedades de la Aorta/etiología , Enfermedades de la Aorta/fisiopatología , Síndrome de Behçet/complicaciones , Síndrome de Behçet/fisiopatología , Síndrome de Budd-Chiari/etiología , Síndrome de Budd-Chiari/fisiopatología , Femenino , Cardiopatías/etiología , Cardiopatías/fisiopatología , Humanos , Inmunosupresores/uso terapéutico , Infecciones , Modelos Logísticos , Masculino , Persona de Mediana Edad , Arteria Pulmonar/fisiopatología , Edema Pulmonar , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Trombosis/etiología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Enfermedades Vasculares/etiología , Enfermedades Vasculares/fisiopatología , Vena Cava Inferior/fisiopatología , Adulto Joven
4.
J Autoimmun ; 62: 67-74, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26162757

RESUMEN

OBJECTIVE: To report the efficacy and safety of anti-TNF agents in patients with severe and/or refractory manifestations of Behçet's disease (BD). METHODS: We performed a multicenter study of main characteristics and outcomes of anti-TNF alpha treatments [mainly infliximab (62%), and adalimumab (30%)] in 124 BD patients [48% of men; median age of 33.5 (28-40) years]. RESULTS: Overall response (i.e. complete and partial) rate was 90.4%. Clinical responses were observed in 96.3%, 88%, 70%, 77.8%, 92.3% and 66.7% of patients with severe and/or refractory ocular, mucocutaneous, joint, gastro-intestinal manifestations, central nervous system manifestations and cardiovascular manifestations, respectively. No significant difference was found with respect to the efficacy of anti-TNF used as monotherapy or in association with an immunosuppressive agent. The incidence of BD flares/patient/year was significantly lower during anti-TNF treatment (0.2 ± 0.5 vs 1.7 ± 2.4 before the use of anti-TNF, p < 0.0001). The prednisone dose was significantly reduced at 6 and 12 months (p < 0.0001). In multivariate analysis, retinal vasculitis was negatively associated with complete response to anti-TNF (OR = 0.33 [0.12-0.89]; p = 0.03). The efficacy and relapse free survival were similar regardless of the type of anti-TNF agent used. After a median follow-up of 21 [7-36] months, side effects were reported in 28% of patients, including infections (16.3%) and hypersensitivity reactions (4.1%). Serious adverse events were reported in 13% of cases. CONCLUSION: Anti-TNF alpha therapy is efficient in all severe and refractory BD manifestations. Efficacy appears to be similar regardless of the anti-TNF agent used (infliximab or adalimumab).


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Síndrome de Behçet/tratamiento farmacológico , Factores Inmunológicos/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/metabolismo , Síndrome de Behçet/mortalidad , Femenino , Humanos , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/efectos adversos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Masculino , Recurrencia , Retratamiento , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
5.
Diagn Interv Imaging ; 96(4): 319-26, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25704146

RESUMEN

Onyx(®) is a remarkable liquid embolizing agent that may allow a well-trained operator to undertake challenging embolization procedures. In multiple interventional radiology indications, the physico-chemical properties of Onyx(®) allow safe embolization. The purpose of this article is to review the advantages and disadvantages of Onyx(®) and identify its main indications.


Asunto(s)
Embolización Terapéutica , Polivinilos , Radiología Intervencionista , Humanos , Polivinilos/farmacología
6.
J Fr Ophtalmol ; 38(2): 159-67, 2015 Feb.
Artículo en Francés | MEDLINE | ID: mdl-25601517

RESUMEN

Diabetic macular edema (DME) is a frequent complication of diabetic retinopathy and may cause severe visual loss. In this article, we examine the pathophysiology of DME and review various treatment options, such as laser photocoagulation, anti-vascular endothelial growth factor (VEGF) receptor antibodies, and steroids including ILUVIEN(®), which is a new sustained-release, non biodegradable, injectable, intravitreal micro-implant containing fluocinolone acetonide. The results of the FAME (Fluocinolone Acetonide in Diabetic Macular Edema) studies, conducted to evaluate the efficacy and safety of ILUVIEN(®) in DME, are discussed.


Asunto(s)
Retinopatía Diabética/tratamiento farmacológico , Implantes de Medicamentos , Fluocinolona Acetonida/administración & dosificación , Edema Macular/tratamiento farmacológico , Enfermedad Crónica , Retinopatía Diabética/complicaciones , Humanos , Inyecciones Intravítreas , Edema Macular/etiología
7.
J Fr Ophtalmol ; 37(7): 566-79, 2014 Sep.
Artículo en Francés | MEDLINE | ID: mdl-25190312

RESUMEN

Age related macular degeneration (AMD) is a pathological aging of the macula, brought about by the interaction of genetic and environmental factors. It induces geographic atrophy of the retina and/or choroidal neovascularization. In the latter, abnormal vessels develop from the choriocapillaris, with the involvement of VEGF (vascular endothelial growth factor). The VEGF family includes several factors, including VEGF-A, B, C, D, F and PlGF (placental growth factor). Their biological properties and their affinities to the VEGFR1, VEGFR2 and VEGFR3 receptors found on endothelial cells differ. Exudative AMD involves mainly VEGF-A and VEGF-R2. Anti-VEGF agents used in ophthalmology (ranibizumab, bevacizumab and aflibercept) are designed to primarily target this pathway. In vitro, all have sufficient affinity to their ligands. Their therapeutic efficacy must therefore be judged based on clinical criteria. In clinical practice, the minimum number of injections required for a satisfactory result appears to be comparable with all the three. The few available studies on therapeutic substitutions of anti-VEGF compounds suggest that some patients may benefit from substituting the anti-VEGF in cases of an unsatisfactory response to an initial molecule. Although local side effects, including increased risk of geographic atrophy, and systemic effects, including vascular accidents, have been suggested, these risks remain low, specially compared to the benefits of the treatment. Differences in safety between anti-VEGF are theoretically possible but unproven.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Degeneración Macular/tratamiento farmacológico , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Envejecimiento/fisiología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Bevacizumab , Neovascularización Coroidal/tratamiento farmacológico , Tolerancia a Medicamentos , Humanos , Degeneración Macular/fisiopatología , Ensayos Clínicos Controlados Aleatorios como Asunto , Ranibizumab , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Retina/fisiología , Factores de Riesgo
8.
Mol Vis ; 20: 908-20, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24966662

RESUMEN

PURPOSE: To evaluate whether anti-vascular endothelial growth factor (VEGF) neutralizing antibodies injected in the vitreous of rat eyes influence retinal microglia and macrophage activation. To dissociate the effect of anti-VEGF on microglia and macrophages subsequent to its antiangiogenic effect, we chose a model of acute intraocular inflammation. METHODS: Lewis rats were challenged with systemic lipopolysaccharide (LPS) injection and concomitantly received 5 µl of rat anti-VEGF-neutralizing antibody (1.5 mg/ml) in the vitreous. Rat immunoglobulin G (IgG) isotype was used as the control. The effect of anti-VEGF was evaluated at 24 and 48 h clinically (uveitis scores), biologically (cytokine multiplex analysis in ocular media), and histologically (inflammatory cell counts on eye sections). Microglia and macrophages were immunodetected with ionized calcium-binding adaptor molecule 1 (IBA1) staining and counted based on their differential shapes (round amoeboid or ramified dendritiform) on sections and flatmounted retinas using confocal imaging and automatic quantification. Activation of microglia was also evaluated with inducible nitric oxide synthase (iNOS) and IBA1 coimmunostaining. Coimmunolocalization of VEGF receptor 1 and 2 (VEGF-R1 and R2) with IBA1 was performed on eye sections with or without anti-VEGF treatment. RESULTS: Neutralizing rat anti-VEGF antibodies significantly decreased ocular VEGF levels but did not decrease the endotoxin-induced uveitis (EIU) clinical score or the number of infiltrating cells and cytokines in ocular media (interleukin [IL]-1ß, IL-6, tumor necrosis factor [TNF]-α, and monocyte chemoattractant protein [MCP]-1). Eyes treated with anti-VEGF showed a significantly decreased number of activated microglia and macrophages in the retina and the choroid and decreased iNOS-positive microglia. IBA1-positive cells expressed VEGF-R1 and R2 in the inflamed retina. CONCLUSIONS: Microglia and macrophages expressed VEGF receptors, and intravitreous anti-VEGF influenced the microglia and macrophage activation state. Taking into account that anti-VEGF drugs are repeatedly injected in the vitreous of patients with retinal diseases, part of their effects could result from unsuspected modulation of the microglia activation state. This should be further studied in other ocular pathogenic conditions and human pathology.


Asunto(s)
Anticuerpos Neutralizantes/uso terapéutico , Activación de Macrófagos/efectos de los fármacos , Microglía/patología , Retina/patología , Uveítis/tratamiento farmacológico , Uveítis/patología , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Anticuerpos Neutralizantes/farmacología , Proteínas de Unión al Calcio/metabolismo , Recuento de Células , Modelos Animales de Enfermedad , Humanos , Lipopolisacáridos , Proteínas de Microfilamentos/metabolismo , Microglía/efectos de los fármacos , Microglía/metabolismo , Pruebas de Neutralización , Óxido Nítrico Sintasa de Tipo II/metabolismo , Ratas , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Retina/efectos de los fármacos , Retina/enzimología , Factor A de Crecimiento Endotelial Vascular/metabolismo
9.
Gene Ther ; 20(11): 1093-103, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23804076

RESUMEN

Inhibition of vascular endothelial growth factor (VEGF) has become the standard of care for patients presenting with wet age-related macular degeneration. However, monthly intravitreal injections are required for optimal efficacy. We have previously shown that electroporation enabled ciliary muscle gene transfer results in sustained protein secretion into the vitreous for up to 9 months. Here, we evaluated the long-term efficacy of ciliary muscle gene transfer of three soluble VEGF receptor-1 (sFlt-1) variants in a rat model of laser-induced choroidal neovascularization (CNV). All three sFlt-1 variants significantly diminished vascular leakage and neovascularization as measured by fluorescein angiography (FA) and flatmount choroid at 3 weeks. FA and infracyanine angiography demonstrated that inhibition of CNV was maintained for up to 6 months after gene transfer of the two shortest sFlt-1 variants. Throughout, clinical efficacy was correlated with sustained VEGF neutralization in the ocular media. Interestingly, treatment with sFlt-1 induced a 50% downregulation of VEGF messenger RNA levels in the retinal pigment epithelium and the choroid. We demonstrate for the first time that non-viral gene transfer can achieve a long-term reduction of VEGF levels and efficacy in the treatment of CNV.


Asunto(s)
Neovascularización Coroidal/genética , Neovascularización Coroidal/terapia , Cuerpo Ciliar/metabolismo , Terapia Genética/métodos , Transfección/métodos , Factor A de Crecimiento Endotelial Vascular/genética , Receptor 1 de Factores de Crecimiento Endotelial Vascular/genética , Animales , Línea Celular , Coroides/metabolismo , Neovascularización Coroidal/metabolismo , Modelos Animales de Enfermedad , Electroporación , Femenino , Angiografía con Fluoresceína , Regulación de la Expresión Génica , Humanos , Neovascularización Patológica/terapia , Plásmidos , Ratas , Epitelio Pigmentado de la Retina/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo
10.
Tissue Antigens ; 79(4): 279-86, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22296171

RESUMEN

Follicular lymphoma (FL) is an indolent, sometimes, fatal disease characterized by recurrence at progressively shorter intervals and is frequently refractive to therapy. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in the human leukocyte antigen (HLA) region on chromosome 6p21.32-33 that are statistically significantly associated with FL risk. Low to medium resolution typing of single or multiple HLA genes has provided an incomplete picture of the total genetic risk imparted by this highly variable region. To gain further insight into the role of HLA alleles in lymphomagenesis and to investigate the independence of validated SNPs and HLA alleles with FL risk, high-resolution HLA typing was conducted using next-generation sequencing in 222 non-Hispanic White FL cases and 220 matched controls from a larger San Francisco Bay Area population-based case-control study of lymphoma. A novel protective association was found between the DPB1*03:01 allele and FL risk [odds ratio (OR) = 0.39, 95% confidence interval (CI) = 0.21-0.68]. Extended haplotypes DRB1*01:01-DQA1*01:01-DQB1*05:01 (OR = 2.01, 95% CI = 1.22-3.38) and DRB1*15-DQA1*01-DQB1*06 (OR = 0.55, 95% CI = 0.36-0.82) also influenced FL risk. Moreover, DRB1*15-DQA1*01-DQB1*06 was highly correlated with an established FL risk locus, rs2647012. These results provide further insight into the critical roles of HLA alleles and SNPs in FL pathogenesis that involve multi-locus effects across the HLA region.


Asunto(s)
Alelos , Predisposición Genética a la Enfermedad , Antígenos de Histocompatibilidad Clase II/genética , Antígenos de Histocompatibilidad Clase I/genética , Linfoma Folicular/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Haplotipos , Humanos , Masculino , Persona de Mediana Edad
11.
Arch Pediatr ; 18 Suppl 2: S79-85, 2011 Jul.
Artículo en Francés | MEDLINE | ID: mdl-21763979

RESUMEN

Retinopathy of prematurity (ROP) is a major cause of visual impairment in premature infants. It is characterized by an arrest in normal retinal vascular development associated with microvascular degeneration, followed by an abnormal hypoxiainduced neovascularization. Recent studies point out that ROP is a multifactorial disease, implicating both oxygen-dependent and oxygen-independent mechanisms. Oxygen-dependent factors leading to microvascular degeneration include generation of reactive oxygen species and suppression of specific oxygen-regulated vascular survival factors, such as vascular endothelial growth factor (VEGF) and erythropoietin. The other major mechanism for the initial capillary loss is oxygen-independent and implicates a deficit in growth factor IGF-1/IGFBP3. The proliferative, second phase of ROP is triggered by increases in vascular growth factors concentrations, in an attempt to compensate for the hypoxic retina. Novel signaling pathways for vascular repair, implicating both metabolite signaling and inflammatory lipids signaling, represent new therapeutic avenues for ROP.


Asunto(s)
Retinopatía de la Prematuridad/epidemiología , Retinopatía de la Prematuridad/fisiopatología , Humanos , Recién Nacido , Factor I del Crecimiento Similar a la Insulina/metabolismo , Estrés Oxidativo/fisiología , Terapia por Inhalación de Oxígeno/efectos adversos , Especies Reactivas de Oxígeno/metabolismo , Neovascularización Retiniana , Factor A de Crecimiento Endotelial Vascular/metabolismo
12.
Ann Pharm Fr ; 69(2): 124-30, 2011 Mar.
Artículo en Francés | MEDLINE | ID: mdl-21440105

RESUMEN

Retinal effects of systemically administered drugs are rare due to the hematoretinal barriers that protect the retina from circulating active principles. However, some compounds may have direct or indirect toxic effects on the retina through direct interaction with a specific receptor or due to their accumulation within pigment of uveal cells. In the latter case, toxicity is dose-dependent and may be observed years after cessation of medication, as observed with antimalarial drugs. Anti-infective and anti-inflammatory agents, particularly glucocorticoids, are currently injected peri- or intraocularly. The mechanisms and the exact toxicity of glucocorticoids on the retina remain poorly understood. More recently, anti-VEGF has been specifically developed for the treatment of retinal diseases. However, the long-term blockade of VEGF on normal retinal physiology should be determined taking into account VEGF and VEGF receptors expression in the normal and pathologic retina. Whilst enormous advances are made in the treatment of retinal diseases, basic research is still required to define more accurately the molecular targets of drugs to improve their benefits and reduce their potential side effects.


Asunto(s)
Retina/efectos de los fármacos , Enfermedades de la Retina/inducido químicamente , Enfermedades de la Retina/tratamiento farmacológico , Corticoesteroides/efectos adversos , Animales , Antiinflamatorios/farmacología , Barrera Hematorretinal/fisiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Fenómenos Fisiológicos Oculares/efectos de los fármacos , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores
13.
Orthop Traumatol Surg Res ; 96(4): 334-9, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20452851

RESUMEN

INTRODUCTION: One possible sequela of obstetric brachial plexus palsy (OP) is impaired external rotation (ER) of the shoulder which, in addition to its functional consequences, can generate a posterior humeral head subluxation or dislocation. The goal of the present study was to assess medium-term clinical and radiological results of release of the subscapularis muscle with transfer of the latissimus dorsi and teres major muscles. PATIENTS AND METHODS: From 1985 to 1995, a continuous series of 32 OP patients underwent subscapularis muscle release, associated in 24 cases to muscle transfer. Mean age was 2.5 years (range, 1-9.2 years). Shoulder function was assessed by measurement of passive ER and graded according to the modified Mallet classification at 1, 5 and 10 years' follow-up or before revision. The evolution of the glenohumeral deformity was assessed on CT images of glenoid retroversion and the humeral head subluxation (% of humeral head covered), before and 5 years after surgery. RESULTS: Mean postoperative follow-up was 9.5+/-5.6 years. Treatment brought significant improvement in passive ER (mean preoperative and 1-year follow-up values: -10 degrees and 52 degrees, respectively). This explained the good modified Mallet score at 1 year: mean=18.4/25. Subsequent significant progressive degradation was noted: 10 years postoperatively, mean ER amplitude and modified Mallet score were respectively 13 degrees and 15.8. The CT study showed correction of the glenoid retroversion (mean preoperative and 5-year follow-up values: 29 degrees and 18 degrees, respectively), and of the humeral head subluxation (mean preoperative and 5-year follow-up values: 25 and 39%, respectively). Surgical revision was indicated six times (five patients): two latissimus dorsi and teres major transfers (not performed initially) and four derotational humeral osteotomies. Three-quarters of the patients who did not initially have muscle transfer had to be reoperated or else showed ER insufficiency at last follow-up. DISCUSSION AND CONCLUSION: Surgical treatment produces objective functional gain, even if this diminishes over time. Moreover, it prevents or corrects posterior subluxation of the shoulder. It is indicated when passive ER amplitude is negative. It seems advisable to associate release to muscle transfer. LEVEL OF EVIDENCE: Level IV Retrospective study.


Asunto(s)
Traumatismos del Nacimiento/cirugía , Neuropatías del Plexo Braquial/cirugía , Lesiones del Hombro , Análisis de Varianza , Traumatismos del Nacimiento/diagnóstico por imagen , Traumatismos del Nacimiento/fisiopatología , Neuropatías del Plexo Braquial/diagnóstico por imagen , Neuropatías del Plexo Braquial/fisiopatología , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Articulación del Hombro/diagnóstico por imagen , Articulación del Hombro/fisiopatología , Articulación del Hombro/cirugía , Estadísticas no Paramétricas , Transferencia Tendinosa/métodos , Tomografía Computarizada por Rayos X
14.
Exp Parasitol ; 126(2): 259-62, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20412796

RESUMEN

Ocular toxoplasmosis is the principal cause of posterior uveitis and a leading cause of blindness. Animal models are required to improve our understanding of the pathogenesis of this disease. The method currently used for the detection of retinal cysts in animals involves the observation, under a microscope, of all the sections from infected eyes. However, this method is time-consuming and lacks sensitivity. We have developed a rapid, sensitive method for observing retinal cysts in mice infected with Toxoplasma gondii. This method involves combining the flat-mounting of retina - a compromise between macroscopic observation and global analysis of this tissue - and the use of an avirulent recombinant strain of T. gondii expressing the Escherichia coli beta-galactosidase gene, visually detectable at the submacroscopic level. Single cyst unilateral infection was found in six out of 17 mice killed within 28 days of infection, whereas a bilateral infection was found in only one mouse. There was no correlation between brain cysts number and ocular infection.


Asunto(s)
Retina/parasitología , Toxoplasma/aislamiento & purificación , Toxoplasmosis Ocular/parasitología , Animales , Encéfalo/parasitología , Modelos Animales de Enfermedad , Femenino , Secciones por Congelación , Ratones , Toxoplasmosis Ocular/diagnóstico
15.
Rev Pneumol Clin ; 66(1): 17-27, 2010 Feb.
Artículo en Francés | MEDLINE | ID: mdl-20207292

RESUMEN

Imaging of mediastinal tumors is an important part of the diagnostic workup in patients presenting symptoms suggestive of compression of one or more of the mediastinal components. In other cases, lesions growing within the mediastinum remain asymptomatic and are diagnosed when chest X-ray or CT are routinely performed for other indications. CT remains the most available and reliable tool among the different imaging methods. Due to its permanent technical improvements, it can be used as the one-step answer to all the requirements of the pretherapeutic evaluation of a mediastinal mass. Chest plain film is still needed as the first line examination in order to carefully select the acquisition protocol for CT. MR did not demonstrate any superiority to CT except for the preoperative workup of lesions arising in the posterior part of the mediastinum. MR remains an interesting tool for tissue characterisation. Topography of mediastinal lesions (based upon the definition of mediastinal compartments) is one of the guides through the diagnostic pathway in imaging these tumors. The other one is their main tissue component, so that cystic, fatty and soft tissue masses can be differentiated.


Asunto(s)
Imagen por Resonancia Magnética , Neoplasias del Mediastino/diagnóstico , Tomografía Computarizada por Rayos X , Diagnóstico Diferencial , Humanos , Metástasis Linfática/patología , Linfoma/diagnóstico , Linfoma/patología , Linfoma/cirugía , Enfermedades del Mediastino/diagnóstico , Enfermedades del Mediastino/patología , Neoplasias del Mediastino/patología , Neoplasias del Mediastino/cirugía , Mediastino/patología , Mediastino/cirugía , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias de Células Germinales y Embrionarias/cirugía , Sensibilidad y Especificidad , Timoma/diagnóstico , Timoma/patología , Timoma/cirugía , Neoplasias del Timo/diagnóstico , Neoplasias del Timo/patología , Neoplasias del Timo/cirugía
16.
Gene Ther ; 16(7): 862-73, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19440225

RESUMEN

Intraocular inflammation has been recognized as a major factor leading to blindness. Because tumor necrosis factor-alpha (TNF-alpha) enhances intraocular cytotoxic events, systemic anti-TNF therapies have been introduced in the treatment of severe intraocular inflammation, but frequent re-injections are needed and are associated with severe side effects. We have devised a local intraocular nonviral gene therapy to deliver effective and sustained anti-TNF therapy in inflamed eyes. In this study, we show that transfection of the ciliary muscle by plasmids encoding for three different variants of the p55 TNF-alpha soluble receptor, using electrotransfer, resulted in sustained intraocular secretion of the encoded proteins, without any detection in the serum. In the eye, even the shorter monomeric variant resulted in efficient neutralization of TNF-alpha in a rat experimental model of endotoxin-induced uveitis, as long as 3 months after transfection. A subsequent downregulation of interleukin (IL)-6 and iNOS and upregulation of IL-10 expression was observed together with a decreased rolling of inflammatory cells in anterior segment vessels and reduced infiltration within the ocular tissues. Our results indicate that using a nonviral gene therapy strategy, the local self-production of monomeric TNF-alpha soluble receptors induces a local immunomodulation enabling the control of intraocular inflammation.


Asunto(s)
Cuerpo Ciliar/metabolismo , Terapia Genética/métodos , Músculo Liso/metabolismo , Receptores Tipo I de Factores de Necrosis Tumoral/biosíntesis , Proteínas Recombinantes de Fusión/biosíntesis , Receptores Señuelo del Factor de Necrosis Tumoral/biosíntesis , Uveítis/terapia , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Electroporación/métodos , Endotoxinas/efectos adversos , Ojo/metabolismo , Femenino , Técnicas de Transferencia de Gen , Genes Reporteros , Humanos , Inmunomodulación , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Operón Lac/genética , Rodamiento de Leucocito , Microscopía Confocal , Óxido Nítrico Sintasa de Tipo II/metabolismo , Plásmidos , Ratas , Ratas Endogámicas Lew , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Recombinantes de Fusión/farmacología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transfección/métodos , Receptores Señuelo del Factor de Necrosis Tumoral/metabolismo , Factor de Necrosis Tumoral alfa/efectos adversos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/metabolismo
17.
Mol Vis ; 15: 670-84, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19347052

RESUMEN

PURPOSE: To analyze the influence of age on retinochoroidal wound healing processes and on glial growth factor and cytokine mRNA expression profiles observed after argon laser photocoagulation. METHODS: A cellular and morphometric study was performed that used 44 C57Bl/6J mice: 4-week-old mice (group I, n=8), 6-week-old mice (group II, n=8), 10-12-week-old mice (group III, n=14), and 1-year-old mice (group IV, n=14). All mice in these groups underwent a standard argon laser photocoagulation (50 microm, 400 mW, 0.05 s). Two separated lesions were created in each retina using a slit lamp delivery system. At 1, 3, 7, 14, 60 days, and 4 months after photocoagulation, mice from each of the four groups were sacrificed by carbon dioxide inhalation. Groups III and IV were also studied at 6, 7, and 8 months after photocoagulation. At each time point the enucleated eyes were either mounted in Tissue Tek (OCT), snap frozen and processed for immunohistochemistry or either flat mounted (left eyes of groups III and IV). To determine, by RT-PCR, the time course of glial fibrillary acidic protein (GFAP), vascular endothelial growth factor (VEGF), and monocyte chemotactic protein-1 (MCP-1) gene expression, we delivered ten laser burns (50 microm, 400 mW, 0.05 s) to each retina in 10-12-week-old mice (group III', n=10) and 1-year-old mice (group IV', n=10). Animals from Groups III' and IV' had the same age than those from Groups III and IV, but they received ten laser impacts in each eye and served for the molecular analysis. Mice from Groups III and IV received only two laser impacts per eye and served for the cellular and morphologic study. Retinal and choroidal tissues from these treated mice were collected at 16 h, and 1, 2, 3, and 7 days after photocoagulation. Two mice of each group did not receive photocoagulation and were used as controls. RESULTS: In the cellular and morphologic study, the resultant retinal pigment epithelium interruption expanse was significantly different between the four groups. It was more concise and smaller in the oldest group IV (112.1 microm+/-11.4 versus 219.1 microm+/-12.2 in group III) p<0.0001 between groups III and IV. By contrast, while choroidal neovascularization (CNV) was mild and not readily identifiable in group I, at all time points studied, CNV was more prominent in the (1-year-old mice) Group IV than in the other groups. For instance, up to 14 days after photocoagulation, CNV reaction was statistically larger in group IV than in group III ((p=0.0049 between groups III and IV on slide sections and p<0.0001 between the same groups on flat mounts). Moreover, four months after photocoagulation, the CNV area (on slide sections) was 1,282 microm(2)+/-90 for group III and 2,999 microm(2)+/-115 for group IV (p<0.0001 between groups III and IV). Accordingly, GFAP, VEGF, and MCP-1 mRNA expression profiles, determined by RT-PCR at 16 h, 1, 2, 3, and 7 days postphotocoagulation, were modified with aging. In 1-year-old mice (group IV), GFAP mRNA expression was already significantly higher than in the younger (10-12 week) group III before photocoagulation. After laser burns, GFAP mRNA expression peaked at 16-24 h and on day 7, decreasing thereafter. VEGF mRNA expression was markedly increased after photocoagulation in old mice eyes, reaching 2.7 times its basal level at day 3, while it was only slightly increased in young mice (1.3 times its level in untreated young mice 3 days postphotocoagulation). At all time points after photocoagulation, MCP-1 mRNA expression was elevated in old mice, reaching high levels of expression at 16 h and day 3 respectively. CONCLUSIONS: Our results were based on the study of four different age groups and included not only data from morphological observations but also from a molecular analysis of the various alterations of cytokine signaling and expression. One-year-old mice demonstrated more extensive CNV formation and a slower pace of regression after laser photocoagulation than younger mice. These were accompanied by differences in growth factors and cytokine expression profiles indicate that aging is a factor that aggravates CNV. The above results may provide some insight into possible therapeutic strategies in the future.


Asunto(s)
Envejecimiento/patología , Argón , Coroides/patología , Coagulación con Láser , Retina/patología , Retina/cirugía , Cicatrización de Heridas , Animales , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Coroides/irrigación sanguínea , Neovascularización Coroidal/patología , Neovascularización Coroidal/cirugía , Regulación de la Expresión Génica , Proteína Ácida Fibrilar de la Glía/genética , Proteína Ácida Fibrilar de la Glía/metabolismo , Ratones , Ratones Endogámicos C57BL , ARN Mensajero/genética , ARN Mensajero/metabolismo , Retina/metabolismo , Epitelio Pigmentado de la Retina/patología , Epitelio Pigmentado de la Retina/cirugía , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo
18.
Rev Laryngol Otol Rhinol (Bord) ; 130(4-5): 211-4, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-20597399

RESUMEN

OBJECTIVES: To compare the diagnostic accuracy between Positron emission tomography using 2-[fluorine-18] fluoro-2-deoxy-D-glucose (FDG-PET scan) and conventional work-up such as ultrasound (US) and/or Computed tomography (CT) in the detection of cervical lymph node recurrences of melanoma of the head and neck after initial cervical lymph node surgery. METHODS: A retrospective review was performed on patients who presented with clinical and/or radiological suspicion of isolated cervical lymph node recurrence after lymph node surgery from April 2004 to January 2007. All patients underwent CT and/or US of the neck, and FDG-PET scan before salvage neck dissection. None of included patients had clinical or radiological detectable distant metastases at the time of the lymph node dissection. Performances of conventional imaging and FDG-PET scan in detection of lymph node recurrence were calculated and compared by using the histopathological results of lymphadenectomy as gold standard with Fischer's exact test. RESULTS: Of the twelve cases in included in the study (9 patients, 3 of them had 2 consecutive lymph node redissection for a second lymph node recurrence), melanoma recurrence was found in 10 cases (83%). Sensitivity, specificity, positive predictive value and negative predictive values were 78.6%, 40%, 78.6%, and 40% respectively for conventional imaging and 85.7%, 40%, 80% and 50% for FDG-PET scan. No statistically significant difference was found between the 2 methods. CONCLUSION: This is the first study that compares the diagnostic accuracy between FDG-PET scan and conventional imaging in the detection of cervical lymph node recurrence of melanoma of the head and neck. Our results showed that FDG-PET scan is actually not better than conventional imaging to detect these cervical lymphatic recurrences.


Asunto(s)
Diagnóstico por Imagen , Neoplasias de Cabeza y Cuello/patología , Melanoma/patología , Recurrencia Local de Neoplasia/diagnóstico , Adolescente , Adulto , Anciano , Femenino , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Metástasis Linfática/diagnóstico , Masculino , Melanoma/cirugía , Persona de Mediana Edad , Disección del Cuello , Estudios Retrospectivos
19.
J Radiol ; 89(7-8 Pt 2): 956-67, 2008.
Artículo en Francés | MEDLINE | ID: mdl-18772774

RESUMEN

Nasopharyngeal carcinoma is relatively common. Undifferentiated Carcinomas of Nasopharyngeal Type (UNCT) are endemic Epstein-Barr virus (EBV)-related tumors. They are mainly radiosensitive. The role of imaging is to assess locoregional extension, TNM classification and adjust the radiation fields. MRI is essential to determine the initial extension. CT is useful to confirm the presence of bone involvement and evaluate nodal status. MRI and CT are necessary for the post-treatment follow-up.


Asunto(s)
Neoplasias Nasofaríngeas/diagnóstico , Humanos , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X
20.
J Radiol ; 89(7-8 Pt 2): 1020-36, 2008.
Artículo en Francés | MEDLINE | ID: mdl-18772779

RESUMEN

Imaging plays a chief role in the care and monitoring of patients in cervico-facial oncology. The radiologist must know the anatomy of different lymph nodes as well as signs of malignancy (hypertrophy, enhancement, necrosis, capsular rupture, etc.). CT is still the first-line examination because of its high reliability, its accessibility and its ability to make an assessment of the upper aero digestive ways at the same time. Ultrasound is very accuracy, and allows the realization of cytoponction, but does not provide a complete exploration of the neck. MRI does not appear to be indicated for the first intention, but the new rapid sequences (STIR, diffusion) seem interesting. The PET-CT is useful in post-therapeutic management of patients, and probably in the initial staging, but its accessibility is poor.


Asunto(s)
Neoplasias de Cabeza y Cuello/diagnóstico , Adulto , Femenino , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Humanos , Metástasis Linfática , Imagen por Resonancia Magnética , Neoplasias de Oído, Nariz y Garganta/diagnóstico , Tomografía Computarizada por Rayos X , Neoplasias Tonsilares/diagnóstico , Ultrasonografía
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