Heart rate turbulence analysis in female patients with fibromyalgia

OBJECTIVE: Fibromyalgia is characterized by diffuse musculoskeletal pain and discomfort. There are several reports regarding autonomic nervous system dysfunction in patients with fibromyalgia. Heart rate turbulence is expressed as ventriculophasic sinus arrhythmia and has been considered to reflect cardiac autonomic activity. Heart rate turbulence has been shown to be an independent and powerful predictor of sudden cardiac death in various cardiac abnormalities. The aim of this study is to determine whether heart rate turbulence is changed in female patients with fibromyalgia compared with healthy controls. METHODS: Thirty-seven female patients (mean age, 40±11 years) with fibromyalgia, and 35 age- and sex-matched healthy female control subjects (mean age, 42±9 years) were included. Twenty-four hours of ambulatory electrocardiography recordings were collected for all subjects, and turbulence onset and turbulence slope values were automatically calculated. RESULTS: The baseline clinical characteristics of the two groups were similar. There were no significant differences in turbulence onset and turbulence slope measures between patients and control subjects (turbulence onset: −1.648±1.568% vs. −1.582±1.436%, p ϝ 0.853; turbulence slope: 12.933±5.693 ms/RR vs. 13.639±2.505 ms/RR, p ϝ 0.508). Although body mass index was negatively correlated with turbulence slope (r ϝ −0.258, p ϝ 0.046), no significant correlation was found between body mass index and turbulence onset (r ϝ 0.228, p ϝ 0.054). CONCLUSION: To the best of our knowledge, this is the first study to evaluate heart rate turbulence in patients with fibromyalgia. It appears that heart rate turbulence parameters reflecting cardiac autonomic activity are not changed in female patients with fibromyalgia. .

Sickle cell retinopathy: diagnosis and treatment / Retinopatia falciforme: diagnóstico e tratamento

Hemoglobinopathies are a group of inherited disorders characterized by quantitative or qualitative malformations of hemoglobin (Hb). Some of these diseases present vaso-occlusive phenomena that are responsible for high morbidity in clinical and/or ophthalmologic terms. Diagnosis of hemoglobinopathies is performed exclusively through hemoglobin electrophoresis. From the ophthalmologic perspective, the most important representative of this group of diseases is sickle cell retinopathy, which presents a wide spectrum of fundus manifestations and may even lead to irreversible vision loss if not properly diagnosed and treated. The aim of this review is to present the classification of sickle cell retinopathy and to describe current management and future perspectives for its treatment, taking into consideration the clinical management of these patients.

As hemoglobinopatias são um grupo de doenças hereditárias caracterizadas por mal-formações quantitativas ou qualitativas da hemoglobina (Hb). Algumas destas doenças podem apresentar fenômenos vaso-oclusivos, responsáveis por alta morbidade do ponto de vista clínico e/ou oftalmológico. O diagnóstico das hemoglobinopatias é feito exclusivamente através da eletroforese de hemoglobinas. Do ponto de vista oftalmológico, a representante mais importante deste grupo de doenças é a retinopatia falciforme, que pode apresentar um amplo espectro de manifestações fundoscópicas, podendo, inclusive, levar à perda visual irreversível se não for corretamente diagnosticada e tratada. O objetivo desta revisão é apresentar a classificação desta doença, a conduta no tratamento atual, bem como suas perspectivas futuras de tratamento, considerando-se as particularidades no manejo clínico destes pacientes.

Perfusion Parameters of Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Patients with Rectal Cancer: Correlation with Microvascular Density and Vascular Endothelial Growth Factor Expression

OBJECTIVE: To determine whether quantitative perfusion parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) correlate with immunohistochemical markers of angiogenesis in rectal cancer. MATERIALS AND METHODS: Preoperative DCE-MRI was performed in 63 patients with rectal adenocarcinoma. Transendothelial volume transfer (Ktrans) and fractional volume of the extravascular-extracellular space (Ve) were measured by Interactive Data Language software in rectal cancer. After surgery, microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression scores were determined using immunohistochemical staining of rectal cancer specimens. Perfusion parameters (Ktrans, Ve) of DCE-MRI in rectal cancer were found to be correlated with MVD and VEGF expression scores by Spearman's rank coefficient analysis. T stage and N stage (negative or positive) were correlated with perfusion parameters and MVD. RESULTS: Significant correlation was not found between any DCE-MRI perfusion parameters and MVD (rs = -0.056 and p = 0.662 for Ktrans; rs = -0.103 and p = 0.416 for Ve), or between any DCE-MRI perfusion parameters and the VEGF expression score (rs = -0.042, p = 0.741 for Ktrans ; r = 0.086, p = 0.497 for Ve) in rectal cancer. TN stage showed no significant correlation with perfusion parameters or MVD (p > 0.05 for all). CONCLUSION: DCE-MRI perfusion parameters, Ktrans and Ve, correlated poorly with MVD and VEGF expression scores in rectal cancer, suggesting that these parameters do not simply denote static histological vascular properties.

Correlação da expressão do receptor do fator de crecimento do epitélio vascular (VEGRF1) e do KI-67, em pacientes com câncer de mama, com variáveis histopatológicas / Correlations of the expression of the receptor of vascular endothelial growth factor (VEGF) and ki-67 with phatological variables in breast cancer patients

Correlação da expressão do receptor do fator de crescimento do epitélio vascular - vascular endothelial growth factor (VEGF) e do KI-67, em pacientes com câncer de mama, com variáveis histopatológicas. Introdução: proteínas que influam na proliferação celular, como o VEGF e o KI-67, são alvo de estudos. O VEGF está implicado na angiogênese, que é necessária ao crescimento tumoral. Objetivo: Analisar a correlação do VEGF e do KI-67 com variáveis histopatológicas. Métodos: entre 15/03/2008 e 14/0412009, incluímos 41 pacientes com câncer de mama inicial, rumores T1 e T2, para estudo, usando a coloração H & E na análise do tumor, grau histológico e invasão vascular e a imunoperoxidade para a avaliação imuno-histoquímica com anticorpos específicos para os receptores de VEGF, KI-67, p53 e receptor de estrogênio (RE), usando escore qualitativo até 3+ na avaliação da intensidade da coloração e/ou quantitativo até 5+, para avaliar a expressão percentual das células coradas. O escore total, soma das duas, pode chegar ao máximo de 8+. Apenas o KI-67 foi categorizado pelo percentual de células coradas na IHQ e considerado positivo a partir de 20%. Resultados: O receptor do VEGFR1, tanto no escore intensidade de cor quanto no escore total, apresenta correlação positiva com os tumores T1 (p=.01), com o receptor estrogênico positivo (p=.01) e com a expressão negativa do KI-67 (p=.02). A expressão do KI-67 apresenta correlação positiva com p53 (p=.00) e com o receptor hormonal negativo (RE-) (p=.04) e correlação fraca com a invasão vascular (p=.09) e o grau histológico indiferenciado (G3) (p=.07). Discussão: A avaliação de marcadores tumorais que possam responder à terapia alvo é um objetivo a ser perseguido. A correlação positiva do VEGF com o status do RE ja foi relatada e está de acordo com nossos resultados. A expressão do KI-67 é associada à pobre evento. Os resultados controversos dos marcadores refletem a dificuldade em padronizar as avaliações (reagentes)...

Correlation of the expression of the receptor of vascular endothelial growth factor (VEGP) and KI-67 with pathological variables in breast cancer patients. Background: Many studies have been conducted on proteins that have action on cell proliferation, such as VEGP and KI-67. VEGP acts in the angiogenesis required for tumor growth. The KI-67 correlates with proliferation of tumor cells, probably reflecting its aggressiveness. Objective: To analyze the correlation of VEGPR1 and KI-67 with pathological variables. Methods: The study was approved by the Committee on Ethics in research, University Hospital of Porto Alegre (RS). Between March 2008 and April 2009 we included 41 patients with early breast cancer (T1 and T2). We used H & E staining for tumor analysis, histological grade and vascular invasion, and immunohistochemistry evaluation with antibodies specific for VEGP receptors, KI-67, p53, estrogen receptor (ER), using quality score until 3+ of the evaluation of intensity of stain and quantitative untiI 5+, to evaluate the expression percentage of stained cells. The total score, add either, can reach 8+ Only the KI-67 was categorized by percentage of stained cells in the IHC and considered positive above 20%. Statistics: correlation and pearson's chi square and, for the significant variables, used the multivariate analysis. Results: The receptor VEGPR1 in both color intensity score and the total score, correlated positively with T1 tumors (p=.01), with the estrogen receptor positive (p=.01) and negative expression of KI-67 (p=.02). The expression of KI-67 correlates positively with p53 (p=.00) and with estrogen receptor negative (p=.04) and weak correlation with vascular invasion (p=.09) and histological grade undifferentiated (p=.07). Discussion: evaluation of tumor markers that may respond to targeted therapy is a goal to be pursued. The positive correlation of VEGP with the status of ER has been reported and is consistent with our results...

Correlations of 3T DCE-MRI Quantitative Parameters with Microvessel Density in a Human-Colorectal-Cancer Xenograft Mouse Model

OBJECTIVE: To investigate the correlation between quantitative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) parameters and microvascular density (MVD) in a human-colon-cancer xenograft mouse model using 3 Tesla MRI. MATERIALS AND METHODS: A human-colon-cancer xenograft model was produced by subcutaneously inoculating 1 x 106 DLD-1 human-colon-cancer cells into the right hind limbs of 10 mice. The tumors were allowed to grow for two weeks and then assessed using MRI. DCE-MRI was performed by tail vein injection of 0.3 mmol/kg of gadolinium. A region of interest (ROI) was drawn at the midpoints along the z-axes of the tumors, and a Tofts model analysis was performed. The quantitative parameters (Ktrans, Kep and Ve) from the whole transverse ROI and the hotspot ROI of the tumor were calculated. Immunohistochemical microvessel staining was performed and analyzed according to Weidner's criteria at the corresponding MRI sections. Additional Hematoxylin and Eosin staining was performed to evaluate tumor necrosis. The Mann-Whitney test and Spearman's rho correlation analysis were performed to prove the existence of a correlation between the quantitative parameters, necrosis, and MVD. RESULTS: Whole transverse ROI of the tumor showed no significant relationship between the MVD values and quantitative DCE-MRI parameters. In the hotspot ROI, there was a difference in MVD between low and high group of Ktrans and Kep that had marginally statistical significance (ps = 0.06 and 0.07, respectively). Also, Ktrans and Kep were found to have an inverse relationship with MVD (r = -0.61, p = 0.06 in Ktrans; r = -0.60, p = 0.07 in Kep). CONCLUSION: Quantitative analysis of T1-weighted DCE-MRI using hotspot ROI may provide a better histologic match than whole transverse section ROI. Within the hotspots, Ktrans and Kep tend to have a reverse correlation with MVD in this colon cancer mouse model.

Sobre-expresión del factor endotelial de crecimiento vascular en blastos leucemicos e implicaciones para el tratamiento de la leucemia mieloide aguda / Over expression of vascular endothelial growth factor in leukaemic blasts and implication for the treatment of acute myeloid leukaemia

Antecedentes: El factor endotelial de crecimiento vascular (VEGF) y su receptor celular VEGFR-2 ya han sido implicados en la via endotelial principal necesaria para la neovascularización tumoral. Aún así, la importancia del sistema VEGF/VEGFR-2 en angiogenesis en tumores hematológicos como la leucemia mieloide aguda (LMA) no ha sido dilucidado. Pacientes y métodos: Evaluación de 32 pacientes con diagnóstico nuevo y no tratado de LMA, mediante inmunohistoquímica de biopsias de médula osea, se hizo comparación con 10 pacientes control. Resultados: La expresión de VEGF y VEGFR-2 fue significantemente mayor en pacientes con mayor grado de densidad microvascular comparado con aquellos con bajo grado (VEGF: p= 0.024; VEGFR-2: p= 0.040) y también mayor que en los controles (P>0.001), mostrando correlación con la densidad microvascular de médula osea. Los pacientes que alcanzaron una remisión completa después de quimioterapia mostraron niveles bajos normales de VEGFR-2. Conclusión: Se encontró evidencia sobre la aumentada expresión de VEGF/VEGFR-2 en blastos leucémicos, así como la correlación con angiogenesis de pacientes con LMA. Esto sugiere que el sistema VEGF/VEGFR-2 puede ser utilizado como objetivo prometedor en las estrategias de terapia antiangiogénica y antileucémica en LMA...

Visualization of Tumor Angiogenesis Using MR Imaging Contrast Agent Gd-DTPA-anti-VEGF Receptor 2 Antibody Conjugate in a Mouse Tumor Model

OBJECTIVE: To visualize tumor angiogenesis using the MRI contrast agent, Gd-DTPA-anti-VEGF receptor 2 antibody conjugate, with a 4.7-Tesla MRI instrument in a mouse model. MATERIALS AND METHODS: We designed a tumor angiogenesis-targeting T1 contrast agent that was prepared by the bioconjugation of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) and an anti-vascular endothelial growth factor receptor-2 (VEGFR2) antibody. The specific binding of the agent complex to cells that express VEGFR2 was examined in cultured murine endothelial cells (MS-1 cells) with a 4.7-Tesla magnetic resonance imaging scanner. Angiogenesis-specific T1 enhancement was imaged with the Gd-DTPA-anti-VEGFR2 antibody conjugate using a CT-26 adenocarcinoma tumor model in eight mice. As a control, the use of the Gd-DTPA-anti-rat immunoglobulin G (Gd-DTPA-anti-rat IgG) was imaged with a tumor model in eight mice. Statistical significance was assessed using the Mann-Whitney test. Tumor tissue was examined by immunohistochemical analysis. RESULTS: The Gd-DTPA-anti-VEGFR2 antibody conjugate showed predominant binding to cultured endothelial cells that expressed a high level of VEGFR2. Signal enhancement was approximately three-fold for in vivo T1-weighted MR imaging with the use of the Gd-DTPA-anti-VEGFR2 antibody conjugate as compared with the Gd-DTPA-rat IgG in the mouse tumor model (p < 0.05). VEGFR2 expression in CT-26 tumor vessels was demonstrated using immunohistochemical staining. CONCLUSION: MR imaging using the Gd-DTPA-anti-VEGFR2 antibody conjugate as a contrast agent is useful in visualizing noninvasively tumor angiogenesis in a murine tumor model.

Angiogênese tumoral como fator prognóstico para disseminaçäo da doença em retinoblastoma / Tumor angiogenesis as a prognostic factor for disease dissemination in retinoblastoma

Objetivos: (1) Avaliar a capacidade angiogênica, quantificada pela medida da área vascular relativa do tumor através da contagem de Chalkley, como possível fator prognóstico em retinoblastoma; e (2) avaliar a invasao de coróide e nervo óptico como fatores prognósticos em retinoblastoma. Métodos: Foram estudados 24 casos de retinoblastoma intra-ocular unilateral, tratados unicamente por enucleaçao do globo ocular, no período entre janeiro de 1992 e dezembro de 1995, no Hospital do Câncer AC Camargo - Sao Paulo. Através do registro de prontuários médicos obteve-se: idade ao diagnóstico, duraçao do acompanhamento e evoluçao clínica, mais especificamente, presença ou ausência de disseminaçao da doença durante o tempo de acompanhamento. Dos blocos de parafina, peças arquivadas e registros de estudo anátomopatológico obteve-se: diâmetro tumoral à macroscopia e revisao histopatológica detalhada de todos os espécimens. A área vascular relativa do tumor foi obtida pela aplicaçao do método de Chalkley em secçoes coradas pelo anticorpo endotélio específico, anti CD 34. Resultados: A idade média ao diagnóstico foi de 37 meses. Cinco pacientes apresentaram doença disseminada (doença orbitária e/ou metástases à distância) em um período médio de 10,4 meses após a cirurgia. Dezenove pacientes nao apresentaram disseminaçao da doença em um tempo de seguimento médio de 53 meses. A Regressao de Cox revelou ser a área vascular relativa do tumor, a única variável capaz de independentemente prever a disseminaçao da doença (p=0.008); a invasao de nervo óptico e coróide nao atingiram significância estatística (p=0.62 and p=0.77 respectivamente). A curva ROC mostrou que o achado de área vascular relativa do tumor igual ou superior a 3,89 por cento, foi altamente sensível (100 por cento) e específico (78,9 por cento) em prever a disseminaçao da doença. Conclusoes: A medida da área vascular relativa do tumor é capaz de prever quais pacientes estao sob risco de desenvolver doença disseminada após a enucleaçao em retinoblastoma intra-ocular. Invasao de coróide e nervo óptico, nao foram fatores de prognóstico significativos nessa série, entretanto o número de casos com esses achados foi muito pequeno para permitir conclusao definitiva. Dessa forma, a avaliaçao da angiogênses pode orientar quais pacientes seriam candidatos a tratamento adjuvante após enucleaçao

Hallazgos con ecografía Doppler color y tomografía computada helicoidal en tumores renales: relación entre volumen y grado de neovascularización / Renal tumors: correlation of volume with neovascularity by means of color Doppler, US and helical CT

Entre julio de 1997 y agosto de 1998, se analizaron en nuestro Servicio 23 neoplasias renales de distinta histología que fueron estudiadas mediante ecografía convencional, Doppler color, Power Doppler y tomografía computada helicoidal, obteniéndose en todos los casos confirmación antomopatológica. Basándonos en sus características volumétricas, los tumores se clasificaron en tres grupos. A la vez, se utilizó Doppler color como power Doppler para caracterizar el tipo e intensidad de neuvascularización tumoral, para obtener distintos registros espectorales, arteriales y venosos, y para calcular las diferentes velocidades de flujo con sus índices de resistencia. Se realizó TC helicoidal, antes y después de la inyección de contraste yodado endovenoso, con el objeto de establecer una correlación entre el volumen ecográfico y el obtenido por tomografía, así como observar los diferentes tipos de realce vascular tumoral y entablar una relación con los hallazgos obtenidos mediante Doppler color y Power Doppler. Los hallazgos deberán ampliarse a un mayor número de casos pero los resultados iniciales indican una importante correlación entre el volumen tumoral y el grado de vascularización en el examen Doppler color, especialmente en tumores de pequeño volumen, con un predominio del patrón hipovascular de los mismos. También se observó un aporte importante de este último en la caracterización de los tumores renales en relación con su histopatología

Etiologies et aspects angiographiques des neovaisseaux sous retiniens

Subretinal neovascularization [SRNV] were a severe disease which could threaten seriously visual function. They were often confined to the vicinity of the fovea and in spite of laser treatment recurrence and blindness were very frequent. Full ophthalmologic examination and fluorescein angiography were performed in thirty nine eyes of twenty seven patients with SRNV - SRNV were unilateral in fifteen cases. Laser treatment was achieved in 24% of cases. Age related macular degeneration [ARMD] and high myopia were the main etiology. Fluorescein angiography allowed to diagnosis of defined SRNV in 92% of cases: 52% at early stages and 40% at glial fibrosis scars. Occult SRNV were noted in the remain cases. 60% of patients had legal blindness. The importance of early angiogrpahy and urgent laser treatment to avoid blindness are raised

ICG-enhanced digital angiography and photocoagulation of choroidal neovascularization in age-related macular degeneration

Choroidal neovascular membranes are often poorly defined on fluorescein angiography because of fluorescein leakage or blockage of hyperfluorescence by overlying hemorrhage, lipid, turbid fluid, or pigment. Indocyanine green (ICG) is a highly protein-bound dye in the near infrared portion of the spectrum. Therefore, ICG remained in and around the neovascular membrane and enhanced the visualization of certain membranes poorly defined with fluorescein. ICG penetrated through the overlying turbid tissue, and improved the visualization of the underlying choroidal neovascular membrane. Using an infrared angiography system, the authors obtained 21 ICG-angiograms with suspected choroidal neovascularization, and compared them to fluorescein angiograms. In 5 of the 21 eyes, occult choroidal neovascularization was well delineated on the ICG angiograms. In 2 eyes, we were able to detect a well-defined choroidal neovascular membrane underlying a subretinal hemorrhage. In 12 of the 21 eyes with choroidal neovascular membrane, we performed argon-green laser photocoagulation applying the overlay technique of the ICG angiogram to red-free photo or the early fluorescein angiogram, and evaluated the effect of full coverage laser treatment.

Neo vascularizaçäo sub-retiniana / Sub retinal neovascular

O surgimento de membranas neo-vasculares sub-retinianas é considerado atualmente como um processo causado pelo afastamento do epitelio pigmentar da membrana de Bruch secundário à formaçäo de drusas ou outras patologias. O reconhecimento clínico destas membranas se faz com a biomicroscopia e com a angiofluoresceinografia. O tratamento convencional é feito pela fotocoagulaçäo com laser de argonio ou kriptonio. Recentemente tem se experimentado o tratamento cirúrgico através da remoçäo mecânica destas membranas

Metodos diagnosticos / Diagnostic methods

La angiografia fluoresceinica es un examen muy importante en el diagnostico de la patologia retinal. La Fundacion Oftalmologica de Santander esta trabajando con una camara angiografica Topcon desde hace 6 anos. El presente articulo revisa la tecnica de realizacion de este examen y presenta la patologia mas frecuentemente encontrada