The combined effect of pravastatin and aspirin on clinical cardiovascular events

The 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, can achieve significant reductions in plasma low-density lipoprotein (LDL)-cholesterol levels. Experimental and clinical evidence now shows that some statins interfere with formation of atherosclerotic lesions independent of their hypolipidemic properties. Vulnerable plaque rupture can result in thrombus formation and artery occlusion; this plaque deterioration is responsible for most acute coronary syndromes, including myocardial infarction (MI), unstable angina, and coronary death, as well as coronary heart diseaseequivalent non-hemorrhagic stroke. Inhibition of HMG-CoA reductase has potential pleiotropic effects other than lipid-lowering, as statins block mevalonic acid production, a precursor to cholesterol and numerous other metabolites. Statins' beneficial effects on clinical events may also thus involve nonlipid-related mechanisms that modify endothelial function, inflammatory responses, plaque stability, and thrombus formation. Aspirin, routinely prescribed to post-MI patients as adjunct therapy, may potentiate statins beneficial effects, as aspirin does not compete metabolically with statins but acts similarly on atherosclerotic lesions. Common functions of both medications include inhibition of platelet activity and aggregation, reduction in atherosclerotic plaque macrophage cell count, and prevention of atherosclerotic vessel endothelial dysfunction. The Cholesterol and Recurrent Events (CARE) trial provides an ideal population in which to examine the combined effects of pravastatin and aspirin. Lipid levels, intermediate outcomes, are examined by pravastatin and aspirin status, and differences between the two pravastatin groups are found. A modified Cox proportional-hazards model with aspirin as a time-dependent covariate was used to determine the effect of aspirin and pravastatin on the clinical cardiovascular composite endpoint of coronary heart disease death, recurrent MI or stroke. Among those assigned to pravastatin, use of aspirin reduced the composite primary endpoint by 35%; this result was similar by gender, race, and diabetic status. Older patients demonstrated a nonsignificant 21% reduction in the primary outcome, whereas the younger had a significant reduction of 43% in the composite primary outcome. Secondary outcomes examined include coronary artery bypass graft (38% reduction), nonsurgical bypass, peripheral vascular disease, and unstable angina. Pravastatin and aspirin in a post-MI population was found to be a beneficial combination that seems to work through lipid and nonlipid, anti-inflammatory mechanisms. ^

The epidemiology of dengue among children less than 18 months of age in Puerto Rico, 1999--2011

Between 1999 and 2011, 4,178 suspected dengue cases in children less than 18 months of age were reported to the Centers for Disease Control and Prevention Dengue Branch in Puerto Rico. Of the 4,178, 813 were determined to be laboratory-positive and 737 laboratory-negative. Those remaining were either laboratory-indeterminate, not processed or positive for Leptospira . On average, 63 laboratory-positive cases were reported per year. Laboratory-positive cases had a median age of 8.5 months. Among these cases, the median age for those with dengue fever was 8.7 months and 7.9 months for dengue hemorrhagic fever. Clinical signs and symptoms indicative of dengue were greatest among laboratory-positive cases and included fever, rash, thrombocytopenia, bleeding manifestations, and petechiae. The most common symptoms among patients who were laboratory-negative were fever, nasal congestion, cough, diarrhea, and vomiting. Using the 1997 WHO guidelines, nearly 50% of the laboratory-positive cases met the case definition for dengue fever, and 61 of these were further determined to meet the case definition for dengue hemorrhagic fever. In comparison, 15% of laboratory-negative cases met the case definition for dengue fever and less than 1% for dengue hemorrhagic fever. None of the laboratory-positive or laboratory-negative cases met the criteria for dengue shock syndrome.^

Angiosarcoma en linfedema crónico posmastectomía : Síndrome de Stewart-Treves

Objetivo: comunicar un caso de angiosarcoma en linfedema crónico posmastectomía, revisar los diagnósticos diferenciales, destacando que el diagnóstico temprano de esta entidad es la única alternativa para poder modificar la evolución tórpida de esta enfermedad. Caso clínico: presentamos una mujer de 78 años con el antecedente de mastectomía izquierda y cobaltoterapia realizadas en 1990, presentando en el año 2000 edema progresivo en miembro homolateral y pared torácica, con la aparición de placas y nódulos rojo-violáceos, indurados, dolorosos desde noviembre de 2006. La extensión y progresión de su enfermedad motivó su internación para corroborar diagnóstico presuntivo de síndrome de Stewart-Treves con biopsias, establecer diagnósticos diferenciales, estudio clínico-oncológico, control del dolor y evaluar posibles tratamientos. Comentarios: 1). El intervalo entre el diagnóstico del carcinoma de mama y el de este cuadro es de 10-20 años. 2). La supervivencia de los pacientes es < 5%. 3). Las posibilidades terapéuticas son agresivas e infructuosas en la mayoría de los casos. 4). El pronóstico depende de la alta sospecha precoz de las lesiones y su extirpación quirúrgica.

Dengue hemorrágico : a propósito de un caso importado en la ciudad de Mendoza : importancia de los antecedentes epidemiológicos : caso clínico

El Dengue es una enfermedad infecciosa, endemo-epidémica, hoy emergente, producida por virus ARN de la familia flaviviridae, que precisa de un vector, mosquitos del género aedes, para ser transmitida al hombre. Los casos que aparecen en nuestro medio son importados, por lo que siempre es importante investigar la epidemiología ante cuadros febriles inespecíficos en pacientes que han estado en zonas endémicas.- Se comunica un caso de dengue hemorrágico importado en una mujer joven con compromiso hepático con el propósito de destacar la importancia de indagar acerca de los antecedentes epidemiológicos y realizar una revisión del tema.

Territorio, trabajo y salud : Una mirada desde dos actividades productivas. Producción granífera en Zona Núcleo y producción ladrillera en el sudeste santiagueño

El objetivo de este artículo es analizar los cambios en la dinámica territorial de la producción de ladrillos en el sudeste santiagueño y de granos en la Zona Núcleo Granífera, y su impacto en la relación urbano-rural y en la salud de los trabajadores. Para ello, recurrimos a técnicas cuantitativas (elaboración de bases de datos sobre la base de registros epidemiológicos institucionales) y a técnicas cualitativas de investigación (entrevistas, observación participante, análisis documental y bibliográfico). En el marco del avance de la frontera agrícola, la sojización y la agriculturización, analizamos la relación entre trabajo y territorio para comprender el proceso de salud-enfermedad-atención en dos zoonosis regionales: enfermedad de Chagas y Fiebre Hemorrágica Argentina

Territorio, trabajo y salud : Una mirada desde dos actividades productivas. Producción granífera en Zona Núcleo y producción ladrillera en el sudeste santiagueño

El objetivo de este artículo es analizar los cambios en la dinámica territorial de la producción de ladrillos en el sudeste santiagueño y de granos en la Zona Núcleo Granífera, y su impacto en la relación urbano-rural y en la salud de los trabajadores. Para ello, recurrimos a técnicas cuantitativas (elaboración de bases de datos sobre la base de registros epidemiológicos institucionales) y a técnicas cualitativas de investigación (entrevistas, observación participante, análisis documental y bibliográfico). En el marco del avance de la frontera agrícola, la sojización y la agriculturización, analizamos la relación entre trabajo y territorio para comprender el proceso de salud-enfermedad-atención en dos zoonosis regionales: enfermedad de Chagas y Fiebre Hemorrágica Argentina

Territorio, trabajo y salud : Una mirada desde dos actividades productivas. Producción granífera en Zona Núcleo y producción ladrillera en el sudeste santiagueño

El objetivo de este artículo es analizar los cambios en la dinámica territorial de la producción de ladrillos en el sudeste santiagueño y de granos en la Zona Núcleo Granífera, y su impacto en la relación urbano-rural y en la salud de los trabajadores. Para ello, recurrimos a técnicas cuantitativas (elaboración de bases de datos sobre la base de registros epidemiológicos institucionales) y a técnicas cualitativas de investigación (entrevistas, observación participante, análisis documental y bibliográfico). En el marco del avance de la frontera agrícola, la sojización y la agriculturización, analizamos la relación entre trabajo y territorio para comprender el proceso de salud-enfermedad-atención en dos zoonosis regionales: enfermedad de Chagas y Fiebre Hemorrágica Argentina

Prothrombin deficiency results in embryonic and neonatal lethality in mice

The conversion of prothrombin (FII) to the serine protease, thrombin (FIIa), is a key step in the coagulation cascade because FIIa triggers platelet activation, converts fibrinogen to fibrin, and activates regulatory pathways that both promote and ultimately suppress coagulation. However, several observations suggest that FII may serve a broader physiological role than simply stemming blood loss, including the identification of multiple G protein-coupled, thrombin-activated receptors, and the well-documented mitogenic activity of FIIa in in vitro test systems. To explore in greater detail the physiological roles of FII in vivo, FII-deficient (FII−/−) mice were generated. Inactivation of the FII gene leads to partial embryonic lethality with more than one-half of the FII−/− embryos dying between embryonic days 9.5 and 11.5. Bleeding into the yolk sac cavity and varying degrees of tissue necrosis were observed in many FII−/− embryos within this gestational time frame. However, at least one-quarter of the FII−/− mice survived to term, but ultimately they, too, developed fatal hemorrhagic events and died within a few days of birth. This study directly demonstrates that FII is important in maintaining vascular integrity during development as well as postnatal life.

Defective placental vasculogenesis causes embryonic lethality in VHL-deficient mice

Inheritance of an inactivated form of the VHL tumor suppressor gene predisposes patients to develop von Hippel–Lindau disease, and somatic VHL inactivation is an early genetic event leading to the development of sporadic renal cell carcinoma. The VHL gene was disrupted by targeted homologous recombination in murine embryonic stem cells, and a mouse line containing an inactivated VHL allele was generated. While heterozygous VHL (+/−) mice appeared phenotypically normal, VHL −/− mice died in utero at 10.5 to 12.5 days of gestation (E10.5 to E12.5). Homozygous VHL −/− embryos appeared to develop normally until E9.5 to E10.5, when placental dysgenesis developed. Embryonic vasculogenesis of the placenta failed to occur in VHL −/− mice, and hemorrhagic lesions developed in the placenta. Subsequent hemorrhage in VHL −/− embryos caused necrosis and death. These results indicate that VHL expression is critical for normal extraembryonic vascular development.

A system for functional analysis of Ebola virus glycoprotein

Ebola virus causes hemorrhagic fever in humans and nonhuman primates, resulting in mortality rates of up to 90%. Studies of this virus have been hampered by its extraordinary pathogenicity, which requires biosafety level 4 containment. To circumvent this problem, we developed a novel complementation system for functional analysis of Ebola virus glycoproteins. It relies on a recombinant vesicular stomatitis virus (VSV) that contains the green fluorescent protein gene instead of the receptor-binding G protein gene (VSVΔG*). Herein we show that Ebola Reston virus glycoprotein (ResGP) is efficiently incorporated into VSV particles. This recombinant VSV with integrated ResGP (VSVΔG*-ResGP) infected primate cells more efficiently than any of the other mammalian or avian cells examined, in a manner consistent with the host range tropism of Ebola virus, whereas VSVΔG* complemented with VSV G protein (VSVΔG*-G) efficiently infected the majority of the cells tested. We also tested the utility of this system for investigating the cellular receptors for Ebola virus. Chemical modification of cells to alter their surface proteins markedly reduced their susceptibility to VSVΔG*-ResGP but not to VSVΔG*-G. These findings suggest that cell surface glycoproteins with N-linked oligosaccharide chains contribute to the entry of Ebola viruses, presumably acting as a specific receptor and/or cofactor for virus entry. Thus, our VSV system should be useful for investigating the functions of glycoproteins from highly pathogenic viruses or those incapable of being cultured in vitro.

Cattle lack vascular receptors for Escherichia coli O157:H7 Shiga toxins

Escherichia coli O157:H7 causes Shiga toxin (Stx)-mediated vascular damage, resulting in hemorrhagic colitis and the hemolytic uremic syndrome in humans. These infections are often foodborne, and healthy carrier cattle are a major reservoir of E. coli O157:H7. We were interested in knowing why cattle are tolerant to infection with E. coli O157:H7. Cattle tissues were examined for the Stx receptor globotriaosylceramide (Gb3), for receptivity to Stx binding in vitro, and for susceptibility to the enterotoxic effects of Stx in vivo. TLC was used to detect Gb3 in tissues from a newborn calf. Gb3 was detected by TLC in kidney and brain, but not in the gastrointestinal tract. Immunohistochemistry was used to define binding of Stx1 and Stx2 overlaid onto sections from cattle tissues. Stx1 and Stx2 bound to selected tubules in the cortex of the kidney of both newborn calves (n = 3) and adult cattle (n = 3). Stx did not bind to blood vessels in any of the six gastrointestinal and five extraintestinal organs examined. The lack of Gb3 and of Stx receptivity in the gastrointestinal tract raised questions about the toxicity of Stx in bovine intestine. We found that neither viable E. coli O157:H7 nor Stx-containing bacterial extracts were enterotoxic (caused fluid accumulation) in ligated ileal loops in newborn calves. The lack of vascular receptors for Stx provides insight into why cattle are tolerant reservoir hosts for E. coli O157:H7.

Mapping a gene causing cerebral cavernous malformation to 7q11.2-q21.

Cerebral cavernous malformation is a common disease of the brain vasculature of unknown cause characterized by dilated thin-walled sinusoidal vessels (caverns); these lesions cause varying clinical presentations which include headache, seizure, and hemorrhagic stroke. This disorder is frequently familial, with autosomal dominant inheritance. Using a general linkage approach in two extended cavernous malformation kindreds, we have identified linkage of this trait to chromosome 7q11.2-q21. Multipoint linkage analysis yields a peak logarithm of odds (lod) score of 6.88 with zero recombination with locus D7S669 and localizes the gene to a 7-cM region in the interval between loci ELN and D7S802.

Os inibidores orais do fator Xa na prevenção de eventos cerebrovasculares em doentes com fibrilhação auricular não-reumática

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Trombocitopenia imune primária crónica : palavra-passe incompleta

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Avaliação da perfusão esplénica em modelo de hemorragia de suíno, após reperfusão com duas soluções fisiológicas distintas

O baço tem importantes funções hematopoiéticas e imunológicas, desempenhando um papel crucial na reposição da hipovolemia e de volume sanguíneo, em situações de hemorragia aguda. A administração de soluções fisiológicas tem grande importância na correção do volume circulante, evitando as complicações de hipovolemia. Este trabalho tem como objetivo avaliar as alterações provocadas no baço, após grave hemorragia dos suínos e reperfusão, utilizando duas soluções fisiológicas distintas, um cristaloide - solução de ringer lactato e um coloide - solução de hidroxietilamido. As lesões histopatológicas encontradas no baço foram congestão, hiperplasia da polpa branca, a notoriedade dos elipsoides e o infiltrado inflamatório, razão pela qual, se procedeu à sua avaliação semi-quantitativa. Relativamente à hiperplasia da polpa branca, foram encontradas diferenças estatisticamente significativas entre o grupo Ringer Lactato e o grupo Hidroxietilamido, verificando-se o aumento da hiperplasia da polpa branca no grupo Ringer Lactato. Quanto à área dos elipsoides, apenas um suíno em cada grupo registava grau 1. Houve uma preponderância do grau 2 no grupo de controlo (n = 5) e no grupo Ringer Lactato (n = 11), enquanto que no grupo Hidroxietilamido se registaram valores idênticos para os graus 2 e 3 (n = 5). A congestão ocorreu em todos os grupos, com predomínio do grau 2 (n = 7) nos grupos Ringer Lactato e Hidroxietilmido. Relativamente ao infiltrado inflamatório, no grupo de controlo predominou o grau 1 (n = 5) e registou-se a prevalência do grau 2 no grupo Ringer Lactato (n = 8) e no grupo Hidroxietilamido (n = 9). A área dos elipsoides variou nos diferentes grupos, não tendo revelado diferenças significativas entre os grupos. Foi observada congestão nos três grupos do estudo, não tendo sido, contudo, registadas diferenças significativas entre os grupos. Quanto ao infiltrado inflamatório, verificou-se que no grupo de controlo predominou o grau 1, enquanto que nos grupos Ringer Lactato e Hidroxietilamido prevaleceu o grau 2, o que se justifica pelo facto dos grupos Ringer Lactato e Hidroxietilamido terem sido submetidos a uma hemorragia. Foi assim possível concluir que a reperfusão volémica com Hidroxietilamido 130/0.4 pode reduzir a hiperreatividade esplénica, quando comparado com o Ringer Lactato, após hemorragia aguda. Verificamos que os elipsoides não sofrem qualquer afetação em situações de alterações hemodinâmicos. Atualizamos um sistema de classificação para avaliação de congestão esplénica, usando o modelo suíno. Aferimos que as situações causadoras de alterações hemodinâmicas ou da perfusão tecidual provocam aumento do infiltrado inflamatório.