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The results of surgical treatment of 127 patients, suffering diabetic foot syndrome, were analyzed. In 82 patients (1st group) a radical toe extirpation was accomplished; in 45 (2nd group)--a phalangopreserving operations (amputaion of toe, necrectomy, sequestrectomy, the abscess opening) were done. The reoperation rate in patients of the 1st group have constituted 6.1%, the wound suppuration -3.6%, in a 2nd group satisfactory results were achieved in 26.7% of patients, and in the rest of them--reoperations were done for the pathological process progression.
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Amputación Quirúrgica/métodos , Desbridamiento/métodos , Diabetes Mellitus Tipo 1/cirugía , Diabetes Mellitus Tipo 2/cirugía , Pie Diabético/cirugía , Dedos del Pie/cirugía , Absceso/patología , Absceso/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Diabetes Mellitus Tipo 1/patología , Diabetes Mellitus Tipo 2/patología , Pie Diabético/patología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reoperación/estadística & datos numéricos , Dedos del Pie/patología , Resultado del TratamientoRESUMEN
In was analyzed diagnostics and treatment results of 32 victims with duodenal injuries. The authors used 3% hydrogen peroxide solution for duodenal rupture diagnosis. Suggested surgical technique includes intestine intersection where it was broken and anastomosis with a loop of small intestine by using of Roux's method. Also it was done duodenal passage temporary shutdown by using of catgut purse-string suture on pyloric part of stomach.
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Procedimientos Quirúrgicos del Sistema Digestivo , Duodeno , Peritonitis , Complicaciones Posoperatorias/prevención & control , Adolescente , Adulto , Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodos , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Drenaje/métodos , Duodeno/diagnóstico por imagen , Duodeno/lesiones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Peritonitis/diagnóstico , Peritonitis/etiología , Peritonitis/cirugía , Radiografía , Rotura/complicaciones , Rotura/diagnóstico , Rotura/etiología , Rotura/cirugía , Técnicas de Sutura , Resultado del TratamientoRESUMEN
In review provides information about the function oft the body of chaperones and their role in the development of pathological processes, including--atherosclerosis and coronary heart disease. Marked comminications systems chaperones to the immune and endocrine systems, and inflammation.
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Chaperonina 60/metabolismo , Enfermedad Coronaria/inmunología , Enfermedad Coronaria/metabolismo , Proteínas HSP90 de Choque Térmico/metabolismo , Proteínas Mitocondriales/metabolismo , Apoptosis/inmunología , Apoptosis/fisiología , Enfermedad Coronaria/patología , Citocinas/biosíntesis , Humanos , Macrófagos/inmunología , Macrófagos/metabolismo , Miocardio/inmunología , Miocardio/metabolismo , Miocardio/patología , Miocitos Cardíacos/inmunología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Pliegue de ProteínaRESUMEN
PURPOSE: To evaluate the clinical and genetic spectrum of inherited retinal diseases (IRDs) in a Kuwaiti tribe. METHODS: Forty four patients with IRDs from 28 nuclear families from the tribe, were evaluated for presenting symptoms, visual acuity, fundus examination, OCT, microperimetry, full-field (ff), and multifocal electroretinography (mERG) and genotyping. RESULTS: Seventeen patients were diagnosed with autosomal recessive retinitis pigmentosa (arRP) associated with RP1 c.606C>A with onset of nictalopia in the third decade, myopia, and macular atrophy by the age of 50; eleven with autosomal recessive cone/rod dystrophy or macular dystrophy associated with RP1 c.606C>A (p.Asp202Glu) mutation with color and central vision deterioration in teenage, myopia, paracentral ring scotoma and macular atrophy; eleven were with arRP associated with PDE6B c.992 + 1 G > A mutation with onset around 5 years, myopia, cataract, retained central fixation, and ellipsoid zone and late perimacular atrophy; five-with Leber congenital amaurosis associated with homozygous RPGRIP1 for c.1107delA mutation with extinguished ffERG and electrophysiological phenotype of rod and cone; and one patient-with autosomal recessive rod-cone dystrophy associated with homozygous PDE6B c.992 + 1 G > A, who was homozygous ABCA4 c.5882 G > A and heterozygous EYS; c.2137 + 1 G > A. CONCLUSIONS: This study represents a typical tribe from the Middle East with high rate of consanguinity for many generations that harbors multiple mutated genes associated with IRD. It demonstrates the predominant phenotype and its variability in retinal disorders caused by identical mutations and illustrates the nuances in the clinical presentation and disease progression of patients with pathogenic mutations in more than one gene.
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Degeneración Macular , Miopía , Distrofias Retinianas , Retinitis Pigmentosa , Transportadoras de Casetes de Unión a ATP/genética , Atrofia , Análisis Mutacional de ADN , Electrorretinografía , Proteínas del Ojo/genética , Humanos , Kuwait/epidemiología , Degeneración Macular/diagnóstico , Degeneración Macular/genética , Mutación , Linaje , Fenotipo , Distrofias Retinianas/diagnóstico , Distrofias Retinianas/genética , Retinitis Pigmentosa/genéticaRESUMEN
PurposePlacental growth factor (PlGF) is a member of the VEGF family that plays an important role in experimental models of diabetic retinopathy and retinal neovascularization. We aimed to investigate whether vitreous levels of PlGF correlated with proliferative diabetic retinopathy (PDR) status, VEGF levels, and bevacizumab treatment. We also analysed PDR membranes to confirm the presence of the PlGF receptor, FLT1, in endothelial cells.MethodsThis was a case-control study: undiluted vitreous fluid samples were obtained from 28 active PDR patients without preoperative bevacizumab treatment, 21 active PDR patients with preoperative bevacizumab treatment, 18 inactive PDR patients, and 21 control patients. PlGF and VEGF levels in samples were determined by enzyme-linked immunosorbent assay. Immunohistochemistry for FLT1 was performed on human PDR membranes.ResultsCompared to control, vitreous PlGF levels were higher in both active PDR without bevacizumab (P<0.0001) and with bevacizumab (P<0.0001). There was no significant difference in PlGF between active PDR patients without and with bevacizumab (P=0.56). Compared to active PDR, PlGF levels were significantly reduced in inactive PDR (P=0.004). PlGF levels were highly correlated with VEGF levels in active PDR. VEGFR1 was expressed in endothelial cells in human PDR membranes.ConclusionThe strong correlation of PlGF levels with PDR disease status and expression of FLT1 in human PDR membranes suggest that PlGF has a pathogenic role in proliferative diabetic retinopathy. Therapeutic targeting of PlGF with agents like aflibercept may be beneficial.
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Inhibidores de la Angiogénesis/uso terapéutico , Bevacizumab/uso terapéutico , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/patología , Factor de Crecimiento Placentario/metabolismo , Neovascularización Retiniana/patología , Cuerpo Vítreo/metabolismo , Biomarcadores/metabolismo , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Humanos , Inmunohistoquímica , Neovascularización Retiniana/cirugía , Arabia Saudita , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Vitrectomía , Cuerpo Vítreo/patologíaRESUMEN
AIMS: To investigate the safety and effectiveness of extrafoveal photodynamic therapy (PDT) occlusion of feeder vessels (FVs) in patients with subfoveal choroidal neovascularisation (CNV) as a result of age related macular degeneration. METHODS: FVs were identified using dynamic fluorescein and indocyanine green angiography with scanning laser ophthalmoscope. The standard doses of verteporfin and laser wavelength were used. The light dose was escalated by increasing the duration of the light dose so the light regimen was 50 J/cm2 for patients 1 and 2; 100 J/cm2 for patients 3, 4, 5; 125 J/cm2 for patients 6 and 7; and 150 J/cm2 for patients 8 and 9. Patients were examined at weeks 1, 4, and 12. RESULTS: The mean improvement on EDTRS chart 3 months after treatment was an increase of 2.1 lines (p = 0.07). Closure of the FV was achieved angiographically in three eyes at various light doses, in three eyes the FV was hypoperfused, and in three eyes the vessels were were neither closed nor hypoperfused. At the last follow up all FVs were reperfused. There was no evidence of retinal damage. CONCLUSION: Verteporfin enhanced FV therapy does not cause subfoveal retinal damage and may have potential to improve central vision in subfoveal CNV caused by exudative macular degeneration. It is not recommended as a monotherapy for CNV.
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Neovascularización Coroidal/tratamiento farmacológico , Degeneración Macular/complicaciones , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Porfirinas/uso terapéutico , Anciano , Anciano de 80 o más Años , Coroides/irrigación sanguínea , Neovascularización Coroidal/etiología , Neovascularización Coroidal/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Degeneración Macular/fisiopatología , Masculino , Proyectos Piloto , Resultado del Tratamiento , Verteporfina , Agudeza VisualRESUMEN
PURPOSE: To investigate the subretinal toxicity profile of the ribozyme to the proliferating cell nuclear antigen (PCNA-Rz) and 5-fluorouracil (5-FU), as well as the highest nontoxic subretinal dose of the mixture of the two agents in rat eyes. METHODS: Brown-Norway rats received subretinal injections of 1 microg, 10 microg, and 100 microg/microl PCNA-Rz and 0.06 microg/microl, 0.3 microg/microl, and 1.5 microg/microl 5-FU in the right eyes, and the left eyes were injected with H-BSS as control. Each dose was tested on 5 eyes in a 5 microl volume. In a second study, a combination of 5-FU (1.5 microg/microL) with varying 10-30-50 microg/microl doses of PCNA-Rz was tested in a regimen of four sequential subretinal injections. Toxicity was monitored by biomicroscopy, indirect ophthalmoscopy, electroretinography (ERG), and histology. RESULTS: The highest nontoxic dose for subretinal PCNA-Rz was 10 microg/microl, whereas 100 microg/microl showed disturbance of pigmentation with corresponding histological changes of retinal photoreceptor loss and retinal pigment epithelium proliferation or irregularities. Subretinal injection of all three doses of 5-FU did not show any toxicity. Serial injections of a mixture of 1.5 microg/microl 5-FU with 10 microg/microl of PCNA-Rz was found to be safe in rat eyes. CONCLUSIONS: Subretinal injections of the combination of PCNA-Rz (10 microg/microl) and 5-FU (1.5 microg/microl) demonstrated to be safe in rat eyes during the course of this study, even with a multiple administration of four injections.
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Fluorouracilo/toxicidad , Antígeno Nuclear de Célula en Proliferación/toxicidad , ARN Catalítico/toxicidad , Retina/efectos de los fármacos , Animales , Combinación de Medicamentos , Electrorretinografía/efectos de los fármacos , Inyecciones , Masculino , Oftalmoscopía , Ratas , Ratas Endogámicas BN , Retina/ultraestructuraRESUMEN
The early pathways underlying the active electric sense of the weakly electric fish Apteronotus leptorhynchus involve three parallel processing streams. An array of tuberous electroreceptors distributed over the skin provides inputs to the electrosensory lateral line lobe (ELL), forming the basis for three topographic maps: LS (lateral segment), CLS (centrolateral segment), and CMS (centromedial segment). In addition, each map receives topographically preserved inputs from a direct feedback pathway. How this feedback contributes to the distinct spatiotemporal filtering properties of ELL pyramidal neurons across maps is not clear. We used an in vitro approach to characterize short-term plasticity (STP) in the direct feedback synapses onto pyramidal neurons in each map. Our findings indicated that the dynamics of STP varied across maps in a manner that was consistent with the temporal filtering properties of pyramidal neurons in vivo. Using a modeling approach, we found that the STP of direct feedback synapses in CMS was best described by a simple facilitation-depression model. On the other hand, STP in LS was best described by synaptic facilitation with a use-dependent recovery rate. These results suggest that differential regulation of overlapping STP processes in feedback pathways can contribute to the functional specialization of topographic sensory maps.
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Mapeo Encefálico , Pez Eléctrico/fisiología , Órgano Eléctrico/fisiología , Plasticidad Neuronal/fisiología , Células Piramidales/fisiología , Sinapsis/fisiología , Animales , Retroalimentación , Femenino , Masculino , Células Receptoras Sensoriales/fisiología , Factores de TiempoRESUMEN
PURPOSE: To assess intra/inter-observer agreement, and diagnostic capabilities of a color fundus photograph, fundus fluorescein angiography (FFA), and spectral domain optical coherence tomography (SD-OCT) in making a diagnosis of myopic choroidal neovascularization (CNV). PATIENTS AND METHODS: Two masked observers evaluated FFA and SD-OCT images to identify the presence of myopic CNV in 80 high-myopic eyes of 57 patients. A third masked observer identified CNV on a color fundus photo. Presence of myopic CNV on a fundus photo was defined as presence of subretinal hemorrhage, thickening of the retina and/or visible membrane at the macula. Presence of myopic CNV on FFA was defined as hyperfluorescence in the early phase with increase in intensity and size in the late phase; presence of a large irregular lesion; and hypofluorsescence due to subretinal hemorrhage. Myopic CNV on SD-OCT was defined as the hyper-reflective lesion with or without intraretinal fluid or subretinal fluid with retinal thickening. RESULTS: Intraobserver repeatability on FFA and SD-OCT was 0.54 and 0.44, respectively. Agreement (kappa) between FFA and SD-OCT was 0.38 and 0.3, respectively. Among 34 eyes, which had the presence of CNV on a color fundus photo, CNV was diagnosed in 18 (53%) eyes on FFA and in 20 (58.8%) eyes on SD-OCT. Sensitivity and specificity of FFA was 47 and 80.4%, respectively, and that of SD-OCT was 58.8 and 86.9%, respectively. CONCLUSION: Repeatability and reproducibility for diagnosis of myopic CNV was better with FFA compared with SD-OCT; however, agreement is very poor between FFA and SD-OCT. SD-OCT is comparatively a better tool to rule out presence of myopic CNV.
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Neovascularización Coroidal/diagnóstico , Angiografía con Fluoresceína , Miopía Degenerativa/diagnóstico , Tomografía de Coherencia Óptica/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neovascularización Coroidal/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Miopía Degenerativa/patología , Variaciones Dependientes del Observador , Fotograbar , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Ferromagnetic resonance properties of F1/f/F2/AF multilayers, where weakly ferromagnetic spacer f is sandwiched between strongly ferromagnetic layers F1 and F2, with F1 being magnetically soft and F2-magnetically hard due to exchange pinning to antiferromagnetic layer AF, are investigated. Spacer-mediated exchange coupling is shown to strongly affect the resonance fields of both F1 and F2 layers. Our theoretical calculations as well as measurements show that the key magnetic parameters of the spacer, which govern the ferromagnetic resonance in F1/f/F2/AF, are the magnetic exchange length (Λ), effective saturation magnetization at T = 0 (m0) and effective Curie temperature (T(C)(eff)). The values of these key parameters are deduced from the experimental data for multilayers with f = Ni(x)Cu(100-x), for the key ranges in the Ni-concentration (x = 54 ÷ 70 at. %) and spacer thickness (d = 3 ÷ 6 nm). The results obtained provide a deeper insight into thermally-controlled spin precession and switching in magnetic nanostructures, with potential applications in spin-based oscillators and memory devices.
RESUMEN
Infiltration of Medicago sativa leaves with a suspension of Pseudomonas syringae pv. pisi elicits the accumulation of several mRNA classes. A clone, designated as MsPR10-1, encoding a polypeptide exhibiting strong similarity to the class 10 PR protein was isolated and characterized from a cDNA library prepared from leaf mRNA. The corresponding gene was shown to be developmentally regulated: Except in roots, its expression was not detectable in other analyzed organs of healthy plants (hypocotyls, cotyledons, stems, leaves, and flower buds). MsPR10-1 transcript accumulation was especially high in leaf blades during an incompatible interaction: It was already detectable 3 h after infection, reached its maximum level 24 h postinfection, and remained at a high level over a period of at least 72 h. In addition, the expression of this gene was induced by salicylic acid treatment of the leaves. Southern hybridizations showed that this gene belongs to a multigene family. Using a 5' extension technique for cDNA, we demonstrated that during the incompatible interaction with P. syringae pv. pisi several genes or allelic variants of this class were expressed. Measurements of transcript accumulation in both the infiltrated and noninfiltrated zones by Northern and in situ hybridization allowed to demonstrate the "systemic" expression pattern of the MsPR10-1. In situ hybridizations indicated that MsPR10-1 was expressed in the vascular bundles adjacent to and distant from the infection site.
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Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Medicago sativa/microbiología , Medicago sativa/fisiología , Proteínas de Plantas/biosíntesis , Pseudomonas/patogenicidad , Transcripción Genética , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , ADN Complementario , Biblioteca de Genes , Hibridación in Situ , Medicago sativa/genética , Datos de Secuencia Molecular , Hojas de la Planta , Proteínas de Plantas/genética , Reacción en Cadena de la Polimerasa , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido NucleicoRESUMEN
The purpose of this study was to determine the production of metalloproteinases (MMP) 2 and 9 following UV-B irradiation in human corneal epithelial cells and fibroblasts. Epithelial cells and fibroblasts were separated from human donor corneas and exposed to UV-B lamp irradiation for 20, 40, 80 and 120 s. Media samples were collected at 8, 24, 48 and 72 h and gelatinase A and B production was assayed by the ELISA test. Statistical significance of production was assessed by the paired t-test. Increased production of MMP-2 was found in human corneal fibroblasts in response to UV-B irradiation. A statistically significant production of MMP-2 was not observed in human corneal epithelial cells following UV-B exposure. We did not detect any increase in MMP-9 after irradiation in either epithelial cells or fibroblasts. MMP-2 is produced by the corneal fibroblasts in the acute phase after UV-B irradiation. MMP-9 is not released in vitro following UV-B irradiation damage and therefore does not directly participate in the pathophysiology of acute photokeratitis.
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Epitelio Corneal/metabolismo , Epitelio Corneal/efectos de la radiación , Fibroblastos/metabolismo , Fibroblastos/efectos de la radiación , Metaloproteinasa 2 de la Matriz/biosíntesis , Metaloproteinasa 9 de la Matriz/biosíntesis , Rayos Ultravioleta , Células Cultivadas , Córnea/metabolismo , Córnea/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Humanos , Técnicas In Vitro , Dosis de RadiaciónRESUMEN
The atmospheric deposition of polycyclic aromatic hydrocarbons (PAHs) was investigated in Hungary by analyzing a moss (Hypnum cupressiforme) species as a bioindicator. In the autumn of 1997, samples were collected at 29 sites distributed across Hungary. The concentrations of total PAH at these sites were in the range of 0.1567-10.45 x 10(4) microg kg(-1) with a mean value of 1.87 x 10(4) microg kg(-1). More than 99% of the total PAHs atmospheric deposition were low molecular weight PAHs (up to 3 ring compounds). The total PAH values showed no correlation with metal concentrations. However, most of the sites in this region showed a positive linear relationship between PAHs levels and traffic volume (r2 = 0.83; P < 0.001) while no relationship existed between PAH levels and population (r2 = 0.01; P > 0.1). Atmospheric deposition of PAHs at different regions in Hungary may be due to incomplete combustion of fuel. The total concentrations of PAHs were compared to the PAH levels in vegetation samples collected from different regions around the world. The highest PAHs concentrations accumulated were found in Hypnum cupressiforme than other vegetation species. A greater affinity for PAH compounds by Hypnum cupressiforme than other moss species probably caused larger amounts of accumulation. A relationship between accumulations of PAH compounds in Hypnum cupressiforme and octanol-air partition coefficients was obtained and is briefly discussed.
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Contaminantes Atmosféricos/análisis , Briófitas/química , Hidrocarburos Policíclicos Aromáticos/análisis , Contaminantes Atmosféricos/farmacocinética , Monitoreo del Ambiente , Hungría , Hidrocarburos Policíclicos Aromáticos/farmacocinéticaRESUMEN
Based upon an analysis of results of gastrectomies in 463 patients with gastric cancer the authors discuss problems of diagnostics, indications for operation, preoperative management, operation technique and postoperative therapy. During the period of from 1967 to 1986 postoperative lethality was reduced from 13.1 to 4.1%.
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Gastrectomía/métodos , Complicaciones Posoperatorias/etiología , Neoplasias Gástricas/cirugía , Femenino , Humanos , Masculino , Cuidados Posoperatorios , Complicaciones Posoperatorias/prevención & control , Cuidados Preoperatorios , Factores de TiempoRESUMEN
The work presents results of surgical treatment of 38 patients with chronic disturbance of duodenal patency. It was established that operations aimed at the improvement of the passage of food through the duodenum, gave unsatisfactory results in remote period in 30% of cases. Operations are recommended aimed at the improvement of the passage of contents of the duodenum in combination with operations excluding the duodenum from the passage of food. Surgical correction of coexistent diseases of the digestive system is recommended.
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Obstrucción Duodenal/cirugía , Adulto , Enfermedad Crónica , Enfermedades del Sistema Digestivo/complicaciones , Enfermedades del Sistema Digestivo/cirugía , Obstrucción Duodenal/complicaciones , Duodeno/cirugía , Femenino , Humanos , Masculino , Métodos , Inducción de RemisiónRESUMEN
A selective proximal vagotomy risk map was created on the basis of risk factors of selective proximal vagotomy (SPV). The severity of initial state of the patient was determined by the map and expressed in scoring system. Four degrees of risk of unfavourable remote results of the operative procedure were established. The result was found to depend on the sum of scored points and risk degree. It was found that recurrent ulcers were most probable after isolated SPV, dumping syndrome followed SPV with the Finney pyloroplasty, other functional disorders took place after SPV with gastroduodenostomy after Jabuley.
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Úlcera Duodenal/cirugía , Vagotomía Gástrica Proximal , Humanos , Pronóstico , Factores de TiempoRESUMEN
Age-related macular degeneration (AMD) is a leading cause of visual impairment in aging populations in industrialized countries. Here we investigated whether the genotype of vascular endothelial growth factor A (VEGFA) gene is associated with response to anti-VEGF therapy. 223 eyes with neovascular AMD were treated with intravitreal anti-VEGF therapy. Responders were defined as patients who had an improvement in best corrected visual acuity (BCVA) of at least 5 letters or one line on the EDTRS visual acuity chart along with resolution of intraretinal or subretinal fluid over 12 months. Patients who did not meet the definition of responders were classified as poor-responders. The vision of responders (n = 148) improved while the vision of poor-responders (n = 75) worsened (P<0.001). Responders on average had a decrease in central foveal thickness (CFT), while poor-responders had an increase in CFT (P <0.001). Compared with the responder group, the poor-responder group had a higher frequency of the risk (T) allele (Allelic P = 0.019) and TT genotype (P = 0.002 under a recessive model) for the VEGFA-rs943080 polymorphism. VEGFA expression was 1.8-fold higher in cells with the VEGFA rs943080 TT genotype than in cells with the VEGFA rs943080 CC genotype (P = 0.012). Age, gender, smoking, diabetes mellitus, and hypertension did not play a significant role in treatment response, but BMI was found to be significantly different between responders and poorresponders (P = 0.033). In conclusion, we demonstrated a potential pharmacogenetic relationship between the VEGFA gene and treatment response to anti-VEGF therapy.The studies are registered at ClinicalTrials.gov under the identifiers NCT00474695 (http://clinicaltrials. gov/ct2/show/NCT00474695) and NCT01464723 (http://clinicaltrials.gov/ct2/show/NCT01464723).
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Polimorfismo de Nucleótido Simple/genética , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/genética , Degeneración Macular Húmeda/tratamiento farmacológico , Degeneración Macular Húmeda/genética , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/farmacología , Bevacizumab , Demografía , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Masculino , RanibizumabRESUMEN
PURPOSE: To determine the genetic basis of early onset autosomal recessive Best vitelliform macular dystrophy (arBVMD) in a family with three affected children. DESIGN: Clinical and family-based genetic study. METHODS: Seven subjects making up a family with three children affected by Best vitelliform macular dystrophy were studied. Standard ophthalmic exam with dilated ophthalmoscopy and imaging were performed in each individual. The eleven exons of BEST1 were directly sequenced. RESULTS: All three affected children have the clinical characteristic features of Best vitelliform macular dystrophy: large macular vitelliform lesions, scattered vitelliform lesions along the arcades and in the peripheral retina, and an accumulation of serous retinal fluid. A novel compound heterozygous mutation in the BEST1 gene was found in the three affected individuals (L41P and I201T). The unaffected parents and children only harbor one heterozygous mutation. CONCLUSION: arBVMD can be caused by the compound heterozygous mutation L41P and I201T in the BEST1 gene.
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Canales de Cloruro/genética , Proteínas del Ojo/genética , Mutación , Distrofia Macular Viteliforme/genética , Adulto , Bestrofinas , Niño , Preescolar , Cartilla de ADN , Exones/genética , Femenino , Genes Recesivos , Humanos , Masculino , Linaje , Agudeza VisualRESUMEN
AIM: To investigate clinical presentation and genotypes in patients with simultaneous geographic atrophy (GA) and choroidal neovascularization (CNV) and to compare with patients with GA or CNV only. PATIENTS AND METHODS: Twenty patients with combined CNV-GA and 154 CNV only and 154 GA only were chosen based on clinical exam and imaging. Six single-nucleotide polymorphisms (SNPs)-rs2274700 and rs1061170 (complement factor H), rs10490924 and rs11200638 (HTRA1/LOC387715), rs2230199 (C3), rs9332739 (C2)-were genotyped using the SNaPshot method. Chi-squared tests were used for genetic analysis. RESULTS: In patients with CNV-GA, GA progressed slowly and often preceded CNV. CNV presented as subretinal haemorrhage or fluid, with a sudden drop in visual acuity (VA). Comparing combined CNV-GA to GA and CNV only, patients with both had a higher frequency of at-risk alleles at both SNPs within the HTRA1 gene-rs10490924 (52.5%), rs11200638 (52.6%). Statistical significance was not achieved. CNV-GA patients had no protective alleles at SNP rs9332739 (C2), compared with GA (27%) and CNV only (10%). CONCLUSION: There is a paucity of reports describing simultaneous CNV-GA. Clinical and genetic results may support the fact that GA and CNV fit on an age-related macular degeneration (AMD)-disease continuum and may clarify the disease processes in AMD.