Factores congénitos de los trastornos trombóticos arteriales en recién nacidos / Congenital factors of arterial thrombotic disorders in newborns

La trombosis arterial neonatal representa el 5,8% de todos los tipos de trombosis conocidos en recién nacidos, esto convierte a esta enfermedad en un punto de enfoque específico para su diagnóstico oportuno, y descifrar los factores congénitos de mayor recurrencia, se realizó una revisión sistemática PRISMA, donde se evaluaron 20 artículos de tipo observacional transversal, detallando los resultados obtenidos en cuanto al factor congénito más recurrente que en este caso es el sexo masculino, prematuridad y defectos genéticos se han mencionado además los marcadores bioquímicos y moleculares mayormente evaluados en esta muestra, demostrando que en estos casos los marcadores bioquímicos analizados con frecuencia son: antitrombina III, Proteína C y S, anticuerpos antifosfolípidos y homocisteína y como marcadores moleculares se evalúa con mayor recurrencia a: Factor V Leiden y el gen de la protrombina G20210A.

Factores congénitos de los trastornos trombóticos arteriales en recién nacidos / Congenital factors of arterial thrombotic disorders in newborns

La trombosis arterial neonatal representa el 5,8% de todos los tipos de trombosis conocidos en recién nacidos, esto convierte a esta enfermedad en un punto de enfoque específico para su diagnóstico oportuno, y descifrar los factores congénitos de mayor recurrencia, se realizó una revisión sistemática PRISMA, donde se evaluaron 20 artículos de tipo observacional transversal, detallando los resultados obtenidos en cuanto al factor congénito más recurrente que en este caso es el sexo masculino, prematuridad y defectos genéticos se han mencionado además los marcadores bioquímicos y moleculares mayormente evaluados en esta muestra, demostrando que en estos casos los marcadores bioquímicos analizados con frecuencia son: antitrombina III, Proteína C y S, anticuerpos antifosfolípidos y homocisteína y como marcadores moleculares se evalúa con mayor recurrencia a: Factor V Leiden y el gen de la protrombina G20210A.

Neonatal arterial thrombosis represents 5.8% of all known types of thrombosis in newborns, this makes this disease a specific point of focus for its timely diagnosis, and to decipher the congenital factors of greater recurrence, a systematic review PRISMA was performed, where 20 articles of cross-sectional observational type were evaluated, detailing the results obtained in terms of the most recurrent congenital factor which in this case is male sex, prematurity and genetic defects have also been mentioned biochemical and molecular markers mostly evaluated in this sample, showing that in these cases the biochemical markers frequently analyzed are: Antithrombin III, Protein C and S, antiphospholipid antibodies and homocysteine and as molecular markers are evaluated with greater recurrence to: Factor V Leiden and the prothrombin gene G20210A.

Narrando histórias, coreografando emoções, no trabalho com o nascimento, a dor e a morte de crianças no hospital / Telling stories and choreographing emotions, at hospital work involving the birth, pain and death of children / Produire des récits, chorégraphier des émotions au travail avec la naissance, la douleur et la mort d'enfants à l'hôpital / Narrando historias, coreografiando emociones, en el trabajo con el nacimiento, el dolor y la muerte de niños en el hospital

Trata-se de uma pesquisa qualitativa baseada em narrativas produzidas por meio de entrevistas e oficinas. O estudo pretende demonstrar como profissionais de saúde de sete especialidades de uma UTI neonatal e pediátrica de um Hospital Público Municipal, no interior do Rio de Janeiro, identificam sinais de sofrimento no trabalho. Esses profissionais lidam com nascimento, dor e morte de crianças, mas não incluem essa experiência como parte integrante de seus cotidianos de trabalho. Aposta-se que o uso de narrativas seja um dispositivo capaz de incluir as dimensões da experiência dos quais tenta-se afastar, bem como produzir conhecimentos sobre a vida e a morte nos processos de trabalho.

This paper describes a qualitative research based on narratives collected by means of interviews and workshops. It aims to reveal in what way health professionals from seven specialties of a neonatal and pediatric ICU of a Municipal Public Hospital in the interior of Rio de Janeiro identify signs of suffering at work. These professionals deal with the birth, pain and death of children, but do not include this experience as an integral part into their daily work. We believe that the use of narratives is a device that allows to incorporate the dimensions of these denied experiences and to produce knowledge about life and death in work processes.

Cette recherche qualitative est basée sur des récits produits à travers d'entretiens et d'ateliers. L'étude a pour but de démontrer de quelle façon des professionnels de la santé de sept spécialités d'une unité de soins intensifs néonatals et pédiatriques d'un hôpital public municipal à l'intérieur de l'état de Rio de Janeiro identifient les signes de souffrance au travail. Ces professionnels sont confrontés à la naissance, la douleur et au décès d'enfants, mais ils n'incluent pas cette expérience dans leur travail quotidien. Nous concluons que la production de récits leur permet d'intégrer les dimensions de l'expérience desquelles ils essaient de se distancer, ainsi que de produire des connaissances sur la vie et la mort au travail.

Se trata de una investigación cualitativa basada en narrativas, producidas mediante encuestas y talleres. El estudio pretende demostrar de qué forma los profesionales de salud de siete especialidades de una UCI neonatal y pediátrica de un hospital público municipal, en el interior de Río de Janeiro, identifican señales de sufrimiento en el trabajo. Estos profesionales se enfrentan con el nacimiento, el dolor y la muerte de niños, pero no incluyen esta experiencia como parte integrante de su vida cotidiana de trabajo. Se apuesta a que el uso de narrativas sea un dispositivo capaz de incluir las dimensiones de la experiencia de las que intenta alejarse, así como producir conocimientos sobre la vida y la muerte en los procesos de trabajo.

Dieser Artikel beschreibt eine qualitative Studie, die auf Erzählungen basiert, die während Interviews und Workshops gesammelt wurden. Die Studie stellt dar, wie Gesundheitspersonal von sieben Fachgebieten einer neonatalen und pädiatrischen Intensivstation eines städtischen Krankenhauses im Inland des Staates von Rio de Janeiro Anzeichen von Leiden bei der Arbeit erkennen. Dieses Personal ist der Geburt, den Schmerzen und dem Tod von Kindern ausgesetzt, berücksichtigt diese Erfahrungen jedoch nicht als wesentlichen Bestandteil seiner täglichen Arbeit. Die Verwendung von Erzählungen ist hier ein Mittel, um die Dimensionen dieser Erfahrungen, die man zu vermeiden versucht, zu verarbeiten (Bruner, 1991) und Wissen über Leben und Tod anhand von Arbeitsprozessen zu produzieren.

First Korean case of factor V Leiden mutation in pregnant woman with a history of recurrent pregnancy loss

Thrombophilia refers to inherited or acquired hemostatic disorders that result in a predisposition to blood clot formation. When combined with the hypercoagulable state that is characteristic of pregnancy, there is an increased risk of severe and recurrent pregnancy complications. Activated protein C resistance caused by factor V Leiden (FVL) mutation is known to be the most common cause of inherited thrombophilia in Caucasian population. FVL mutation has been related to pregnancy complications associated with hypercoagulation, e.g. miscarriage, intrauterine fetal demise, placental abruption, and intrauterine growth retardation. Although the FVL mutation is easily detected using molecular DNA techniques, patients who are heterozygous for this disorder often remain asymptomatic until they develop a concurrent prothrombotic condition. Because there are potentially serious effects of FVL mutation for pregnancy, and because effective treatment strategies exist, early detection and treatment of this condition might be considered.

Anti-phospholipid syndrome in seven leprosy patients with thrombotic events on corticosteroid and/or thalidomide regimen: insights on genetic and laboratory profiles

Abstract INTRODUCTION Corticosteroids and/or thalidomides have been associated with thromboembolism events (TBE) in multibacillary (MB) leprosy. This report aimed to determine genetic and laboratory profiles associated with leprosy and TBE. METHODS Antiphospholipid antibodies (aPL), coagulation-related exams, prothrombin and Leiden's factor V mutations, and ß2-glycoprotein-I (ß2GPI) Val247Leu polymorphism were assessed. RESULTS Six out of seven patients with leprosy were treated with prednisone and/or thalidomide during TBE and presented at least one positive aPL. All patients presented ß2GPI polymorphism, and one showed prothrombin mutation. CONCLUSIONS Corticosteroid or thalidomide adverse effects and aPL and ß2GPI polymorphisms may cause TBE in patients with MB leprosy.

Sentimentos de mulheres em sofrimento psíquico grave acerca de suas vivências sexuais / Feelings of women in severe psychic suffering regarding their sexual experiences / Sentiments de femmes en souffrance psychique grave au sujet de leurs expériences sexuelles / Sentimientos de mujeres en sufrimiento psíquico grave sobre sus vivencias sexuales

Objetivo Conhecer os sentimentos relacionados à vivência da sexualidade em mulheres no processo de sofrimento psíquico grave. Procedimentos Foram realizados grupos de rodas de conversas, e seus resultados foram analisados levando-se em consideração o discurso emergente nas falas das mulheres por meio dos significados que as participantes e/ou pesquisadora atribuíram aos fatos. Conclusões As formas de subjetivação acerca da sexualidade interferem no modo como as mulheres participantes do estudo a vivenciam, provocando os mais diversos sentimentos contraditórios.

Objective To know the feelings related to the experience of sexuality in women in the process of severe psychic suffering. Procedures groups of conversation were conducted, and their results were analyzed taking into account the discourse emerging from the women's speeches through the meanings that the participants and/ or researcher attributed to the facts. Conclusions the forms of subjectivation about sexuality interfere in the way the women participating in the study experience it, provoking the most diverse contradictory feelings.

Objectif Examiner les sentiments liés à l'expérience de la sexualité de femmes en souffrance psychique grave. Procédures des groupes discussions ont menés des conversations et les résultats ont été analysés en tenant compte du discours émergent des déclarations de femmes à travers les significations que les participantes et/ ou la chercheuse attribuent aux faits. Conclusions les formes de subjectivation de la sexualité interfèrent dans la façon dont les femmes la vivent, ce qui provoque de divers sentiments contradictoires.

Objetivo conocer los sentimientos relacionados a la vivencia de la sexualidad en mujeres en proceso de sufrimiento psicológico grave. Procedimiento se llevaron a cabo conversaciones grupales, y los resultados se analizaron teniendo en cuenta el discurso emergente, en los comentarios de las mujeres, a través de los significados que las participantes y/o investigadoras atribuyeron a los hechos. Conclusiones las formas de subjetivación sobre la sexualidad interfieren en la forma en la que las mujeres que participaron en el estudio la vivencian, provocando los más diferentes sentimientos contradictorios.

Ziel Gefühle von Frauen mit schweren psychischen Leiden zu erkunden, die im Zusammenhang mit sexuellen Erfahrungen entstehen. Verfahren Gesprächskreise wurden gebildet und die Ergebnisse wurden analysiert unter Berücksichtigung der Berichte von Frauen und den Bedeutungen, welche die Teilnehmerinnen und/ oder die Forscherin den Tatsachen zuordnet. Schlussfolgerungen die Formen der Subjektivierung der Sexualität interferieren in der Art und Weise wie diese Frauen ihre Sexualität leben, was somit die verschiedensten widersprüchlichen Gefühle zur Folge hat.

Trombofilias hereditarias / Hereditary Thrombophilia

Las trombofilias hereditarias suponen un grupo de enfermedades que predisponen al desarrollo de enfermedad tromboembólica arterial y venosa, debido a déficit o ganancia de función de factores anticoagulantes o procoagulantes incrementando de manera significativa la morbilidad y mortalidad en la población adulta y pediátrica. La expresión y penetrancia genética de este grupo de enfermedades es diversa, y las formas de presentación clínica varía desde la purpura fulminans neonatal hasta episodios tromboembólicos recurrentes a edades tempranas y efectos adversos en el embarazo. El screening no es rutinario en pacientes con cuadros tromboembólicos y sus indicaciones son precisas, en especial personas menores a los 45 años, con cuadros recurrentes, y abortos o muertes fetales a repetición sin causa específica. El tratamiento es basado de acuerdo a la presentación del cuadro clínico, sin embargo la anticoagulación convencional es ampliamente utilizada en el manejo de este grupo de pacientes.

Inherited thrombophilia represent a group of diseases that predispose to the development of arterial and venous thromboembolic disease due to deficiency or gain of function of anticoagulant or procoagulant factors, increasing significantly the morbidity and mortality in the adult and pediatric population. Expression and genetic penetrance to this group of diseases is diverse, and the form of clinical presentation varies from the neonatal purple fulminans to recurrent thromboembolic events at a young age and pregnancy with side effects. The screening is not routine in patients with thromboembolic condition and its indications are accurate, especially in younger people than 45, with recurrent episodes of abortions or fetal deaths without specific cause. Treatment is based according to the clinical presentation of the condition; however conventional anticoagulation is widely used in the treatment of this patient group.

Inherited thrombophilia profile in patients with recurrent miscarriages: Experience from a tertiary care center in north India

The cause of recurrent miscarriage (RM) remains unexplained in approximately 30% to 50% cases. The association of inherited thrombotic factors and RM patients has not been documented from the northern part of India. A total of 40 patients had been investigated for inherited thrombophilia workup (protein C, protein S [PS], antithrombin III, and factor V Leiden [FVL] mutation) over a period of 10 years (2005 to 2014). RM patients were divided in to three groups. Group I (only 1st trimester loss), group II (only 2nd and 3rd trimester), and group III (mixed). Each group comprised of the following numbers of patients respectively: I, 24; II, 2; III, 14. Heterozygous FVL mutation was found in 10% (4/40) cases. PS deficiency was detected in 2.7% (1/37) cases. In the present study FVL and PS were seems to be associated with a subset of patients however further studies with larger numbers of patients are recommended for better evaluation.

Comparison of the Real-Time PCR Tests for Factor V G1691A and Prothrombin G20210A with PCR-Restriction Fragment Length Polymorphism and Direct Sequencing Tests / 임상검사와정도관리

BACKGROUND: Factor V (FV) G1691A and prothrombin G20210A mutations are the most common targets of genetic tests for thromboembolism. This study compared the ability of real-time PCR to detect FV G1691A and prothrombin G20210A (BioSewoom, Korea) with that of PCR-restriction fragment length polymorphism (RFLP) and direct sequencing, to evaluate diagnostic equivalency. METHODS: Real-time PCR was compared with PCR-restriction fragment length polymorphism (RFLP) and direct sequencing using patients' samples as well as heterozygous and homozygous World Health Organization (WHO) reference reagent DNA. The limit of detection (LoD) for real-time PCR was determined using WHO reference reagents. RESULTS: All 141 and 156 patient samples were tested for the FV G1691A and prothrombin G20210A mutations, respectively; the results from all three methods (real-time PCR, PCR-RFLP, and direct sequencing) consistently showed that the samples were wild type. Each of the three methods showed the same results in tests using heterozygous and homozygous DNA from the WHO reference reagents. The LoD of wild type and homozygous samples was 65.16 pg/mL for FV G1691A, and 61.3 pg/mL for prothrombin G20210A. The LoD of heterozygous samples was 1,650.0 pg/mL for FV G1691A and 1,640.0 pg/mL for prothrombin G20210A. CONCLUSIONS: The real-time PCR test kits for FV G1691A and prothrombin G20210A showed reliable equivalency with PCR-RFLP and direct sequencing, and could be useful tests to detect gene polymorphisms for thromboembolism.

Síndrome de Budd Chiari: Reporte de tres casos y revisión de la literatura / Budd Chiari Syndrome: Three Case Reports and a Literature Review

Se describen los casos de tres pacientes de sexo femenino a quienes se les hizo diagnóstico de síndrome de Budd Chiari. En una paciente la presentación del síndrome fue subaguda, pudiendo ser manejada exitosamente con la colocación de TIPS. Otra con mutación del factor V Leyden asociada desarrolló disfunción hepática progresiva y requirió de trasplante hepático. En dos de los tres casos se identificó una enfermedad hematológica como trastorno de base, y en uno el uso de anticonceptivos orales como factor de riesgo. Las tres pacientes fueron sometidas a terapia anticoagulante y el manejo quirúrgico fue definido de acuerdo a su condición clínica. Sin embargo, en un caso la presentación fue aguda con falla hepática y muerte.

This article describes the cases of three female patients who were diagnosed with Budd-Chiari syndrome. One patient was subacute and could be successfully managed by placement of a transjugular intrahepatic portosystemic stent (TIPS). Another patient who had the Factor V Leiden mutation developed associated progressive liver dysfunction and required liver transplantation. A hematologic disease was identified as the underlying disorder in two of the three cases. For one patient, the use of oral contraceptives was a risk factor. Since all three patients were undergoing anticoagulant therapy, surgical management was determined according to each patient’s clinical condition. Nevertheless, the one patient who that presented acute hepatic failure did not survive.

Saúde mental e vulnerabilidade social: a direção do tratamento / Mental health and social vulnerability: direction of the treatment / Santé mentale et vulnérabilité sociale: la direction du traitement / Salud Mental y vulnerabilidad social: la dirección del tratamiento

O objetivo do texto é refletir sobre as relações entre saúde mental e vulnerabilidade social a partir do encontro da Psiquiatria Biológica com a Reforma Psiquiátrica. Problematizamos o conceito de saúde mental, o conceito de vulnerabilidade social, os manuais diagnósticos, as pesquisas epidemiológicas, tendo como pano de fundo as Políticas Públicas de Saúde. Identificamos a necessidade de superação da lógica técnico-científico tradicional incorporando a singularidade e saberes ligados aos sujeitos que são afetados pelo sofrimento.

The aim of this paper is to reflect on the relationship between mental health and social vulnerability at the intersection of biological psychiatry and the Brazilian psychiatric reform. The concepts of mental health and social vulnerability, as based on diagnostic manuals and epidemiological research, are taken up in the scope of public health policies. We identify the need to overcome the traditional technical and scientific logic to incorporate the singularity and knowledge related to human suffering.

L'objectif de cet article est de réfléchir sur les rapports entre la santé mentale et la vulnérabilité sociale à partir de la rencontre entre la Psychiatrie biologique et la Réforme psychiatrique. On problématise les concepts de santé mentale et de vulnérabilité sociale, les manuels de diagnostic, les recherches épidémiologiques, en prenant comme base les Politiques publiques de santé. On a identifié la nécessité de dépasser la logique technique et scientifique traditionnelle en intégrant la singularité et les savoirs liés aux sujets qui sont touchés par la souffrance.

El objetivo de este trabajo es reflexionar sobre la relación entre la salud mental y la vulnerabilidad social a partir del encuentro de la Psiquiatría Biológica y la Reforma Psiquiátrica. Problematizamos los conceptos de salud mental y de vulnerabilidad social, los manuales de diagnóstico, las investigaciones epidemiológicas, teniendo como telón de fondo a las Políticas de Salud Pública. Se identificó la necesidad de superar la lógica tradicional técnica y científica incorporando la singularidad y los conocimientos relacionados con los sujetos que son afectados por el sufrimiento.

Fatores de risco hereditários e adquiridos na coagulação: impacto no desenvolvimento de eventos tromboembólicos em pacientes com lesão medular causada por trauma raquimedular / Hereditary and acquired clinical risk factors in the coagulation: impact in the development of thromboembolic events in patients with spinal injury caused by spinal cord injury

Objetivo: Avaliar o impacto de fatores de risco no desenvolvimento de eventos tromboembólicos em pacientes com lesão medular. Métodos: Estudo observacional, prospectivo e cruzado. Pacientes elegíveis (n=100) tinham lesão medular por trauma raquimedular e mais de 18 anos. O grau de lesão sensorial e motora foi avaliado com base na escala ASIA (ASIA Impairment Scale - AIS). Amostras de sangue foram coletadas para exames de coagulação, hemogramas, análises bioquímicas e laboratoriais. Exames de ultrassonografia foram realizados nos sistemas venosos superficial e profundo dos membros inferiores. Experimentos de PCR em tempo real foram realizados com o intuito de investigar mutações nos genes da protrombina (G20210A) e do fator V de Leiden (G1691A). Resultados: O principal achado deste estudo foi a maior ocorrência de Trombose Venosa Profunda (TVP) em pacientes com fator V de Leiden e hiperhomocisteinemia. Não houve associação entre Lesão Medular por TVP, Tromboembolismo Venoso (TEV) e trombofilia. Não houve também relação com lúpus anticoagulante e anti-cardiolipina. Conclusões: Houve importante diferença na incidência de TVP em pacientes com Lesão Medular, tanto aguda quanto crônica (após um ano da lesão). A investigação de trombofilia deve ter como base os fatores clínicos, fatores de risco para TVP e história familiar de trombose

Objective: Evaluate the impact of risk factors in the development of thromboembolic events in patients with spinal cord injury. Design: Observational, prospective and cross study. Eligible patients (n=100) had spinal injury (SI) by spinal cord injury (SCI), older than 18 years of age. The degree of motor and sensory lesion was evaluated based on ASIA Impairment Scale (AIS). Blood samples were collected for coagulation exams, hemogram, laboratory and biochemical analyses. Ultrasonography analyzes were performed from deep and superficial venous systems of lower limbs. Quantitative real-time PCR experiments were performed in order to investigate mutations in the prothrombin (G20210A) and Leiden factor V (G1691A) genes. Results: The main finding of this study was the higher occurrence of Deep Venous Thromboembolism (DVT) in patients with Leiden factor V and hyper homocysteinemia. There was no association between SI for DVT, venous thromboembolism (VT) and thrombophilia. Also, there was no relation between lupus anticoagulant and anti-cardiolipin. Conclusions: There is an important difference in the incidence of DVT in patients with SI by acute SCI and after 1 year. The conduct of the investigation for thrombophilia should be based on clinical factors, risk factors for DVT and family history of thrombosis

Prevalence of thromogenic gene mutations in women with recurrent miscarriage: A retrospective study of 1,507 patients

OBJECTIVE: Thromogenic gene mutations has been thought to be associated with recurrent pregnancy loss in women in Turkey. The aim of this study was to investigate the prevalence of thromogenic gene mutations such as factor V Leiden (FVL, G1691T), prothrombin (G20210A), and the methylene tetrahydrofolate reductase (MTHFR, C677T) mutation in women with recurrent pregnancy loss. METHODS: This descriptive study was carried out in the Department of Obstetrics and Gynaecology, Harran University School of Medicine, and included a total of 1,507 women with histories of recurrent pregnancy loss between January 2010 and June 2013. The mutations were assessed by using the polymerase chain reaction. RESULTS: The homozygous mutation frequencies of FVL, prothrombin, and MTHFR were found to be 3 (0.20%), 0 and 125 (8.29%), and the heterozygous mutation frequencies were 83 (5.51%), 61 (4.05%), and 612 (40.61%), respectively. Among the 86 FVL mutation patients, 38 also had accompanying prothrombin and MTHFR mutations. CONCLUSION: Since the homozygous forms of the FVL-prothrombin gene mutations have low incidences and MTHFR mutation is similar to a healthy population, preconceptional thromogenic gene mutations screening seems to be controversial.

Analysis of factor V Leiden and prothrombin mutations in patients with suspected thrombophilia in São Paulo state-Brazil / Análise da mutação no fator V de Leiden e na protrombina em pacientes do estado de São Paulo, Brasil

INTRODUCTION: Prothrombin (factor II) is a thrombin precursor, which induces fibrin formation. A mutation in the prothrombin gene (G20210A) has been described, which is directly associated with high prothrombin levels, hence thrombophilia. G1691A mutation in the factor V Leiden (FVL) gene occurs on exon 10, one of the main cleavage sites for protein C activation, resulting in protein alteration. OBJECTIVE: To identify and estimate the genotype frequency of the three possible genotypes and the frequency of the two existing alleles in the FVL and prothrombin genes in patients with suspected thrombophilia in the state of Sao Paulo. This study may provide more literature and reference data on the incidence of prothrombin genotypes among individuals in Brazil. MATERIAL AND METHODS: Analysis of point mutation by real time polymerase chain reaction (RT-PCR). RESULTS: We obtained a total of 100 individuals, from which 94% had the homozygous G genotype. Only 6% had heterozygous genotype and there was no individual with the homozygous genotype A for FVL gene. As to the prothrombin gene, the frequency was 97% for homozygous G genotype and 3% for the heterozygous genotype. There was no patient with the homozygous A genotype. CONCLUSION: This study demonstrated that the genotype identification of these genes is advisable for patients with suspected thrombophilia in this region.

INTRODUÇÃO: A protrombina (fator II) é a precursora da trombina, que induz a formação de fibrina. Foi descrita uma mutação no gene da protrombina (G20210A), associado diretamente a altos níveis de protrombina no sangue e, consequentemente, a trombofilia. A mutação G1691A no gene do fator V de Leiden (FLV) localiza-se no éxon 10, resultando na alteração da proteína, um dos principais sítios de clivagem para ativação da proteína C. OBJETIVOS: Identificar e estimar a frequência genotípica dos três possíveis genótipos, assim como estimar a frequência dos dois alelos existentes no gene do FLV e na protrombina em pacientes com suspeita de trombofilia no estado de São Paulo. Este estudo poderá fornecer mais dados para a literatura e para consulta da incidência dos genótipos da protrombina em indivíduos no Brasil. MATERIAL E MÉTODOS: Análise de mutação pontual por reação em cadeia da polimerase em tempo real (RT-PCR). RESULTADO: Obtivemos o número de 100 indivíduos e, desse total, 94% possuíam o genótipo para homozigoto G; apenas 6%, genótipo heterozigoto; nenhum indivíduo foi encontrado com genótipo homozigoto A no gene do FLV. No gene da protrombina, a frequência foi de 97% para o genótipo homozigoto G e 3% para o genoma heterozigoto; não foi encontrado nenhum indivíduo com o genoma homozigoto A. CONCLUSÃO: Este estudo mostrou que é recomendável a identificação do genótipo para esses genes em pacientes com suspeita de trombofilia nessa região.

Alterações genéticas em casais com antecedentes de aborto recorrente no primeiro trimestre da gestação / Genetic alterations in couples with a history of recurrent miscarriage in the first trimester of pregnancy

O abortamento é considerado um problema multifatorial, cujas principais causas envolvidas na sua etiologia são os fatores ambientais (como exposição a substâncias tóxicas), genéticos, anatômicos, endócrinos, imunológicos, trombofílicos e doenças infecciosas (como toxoplasmose, rubéola). No entanto, os fatores genéticos são atribuídos principalmente aos abortamentos de primeiro trimestre da gestação. As alterações cromossômicas, o polimorfismo C677T, no gene da metilenotetrahidrofolato redutase (MTHFR677C>T); o polimorfismo G1691A, no gene do Fator V de Leiden (FVL1691G>A), e o polimorfismo G20210A, no gene da protrombina (PRT20210G>A), têm sido associados a problemas obstétricos, incluindo aborto recorrente. O objetivo deste trabalho foi investigar associação entre as mutações relacionadas à trombofilia, presença de alterações cromossômican e a ocorrência de aborto espontâneo recorrente e avaliar possíveis interações entre as referidas mutações e as alterações cromossômicas. A casuística foi composta por 151 mulheres com história de aborto recorrente, 94 parceiros e 100 controles (mulheres sem histórico de aborto). A investigação das mutações foi realizada pela técnica de Reação em Cadeia da Polimerase- Polimorfismo de Tamanho de Fragmento de Restrição. As alterações cromossômicas foram investigadas pela cariotipagem com banda–G. A frequência das alterações cromossômicas foi de 7,3% nas mulheres com abortamento recorrente e 1% nos controles (p=0,022), e de 2,1% nos parceiros. No entanto, a frequência dos alelos MTHR677C>T (23% versus 22,5%), FVL1691G>A (1,5% versus 1% ) e PRT20210G>A (1,45% versus 0%) foi similar entre casos e controles, respectivamente. No grupo investigado, foi observada associação entre aborto recorrente e alterações cromossômicas, mas não foi encontrada associação com os polimorfismos gênicos investigados.

Abortion is considered a multifactorial problem, the most important causes involved in its etiology are, environmental factors ( as exposure to toxic chemicals), genetic, anatomic, endocrine, immunological, thrombophilic and infectious diseases (such as toxoplasmosis, rubella). However, genetic factors are mainly attributed to abortions of the first trimester of pregnancy. Chromosomal abnormalities, MTHFR 677C>T, factor V Leiden 1691G>A and prothrombin 20210G>A mutations have been associated with obstetric problems, including recurrent miscarriage. The objective of this research was to investigate associations between mutations in three genes commonly associated to thrombophilic events, chromosomal abnormalities and the occurrence of recurrent miscarriage. As well evaluate possible interactions between these mutations and chromosomal abnormalities. The sample was comprised of 151 women with history of recurrent miscarriages, 94 partners and 100 control (women with no history of abortion). The investigation of the mutations was performed by Polymerase Chain Reaction (PCR)/ Restriction Fragment Length Polymorphism (RFLP). Chromosomal aberrations were investigated by karyotyping with G-banda. The frequency of chromosomal abnormalities was 7.3% in women with recurrent miscarriage and 1% in controls (p = 0.022), and 2.1% in the partners. However, the frequency of allele MTHR677C> T (23% versus 22.5%), FVL1691G> A (1.5% vs. 1%) and PRT20210G> A (1.45% vs. 0%) was similar for cases and controls, respectively. In the investigated group was found association between recurrent miscarriage and chromosomal abnormalities, but no association was found with the genetic polymorphisms investigated.

O psicanalista no tratamento da dor / The psychoanalyst in the treatment of pain / Le psychanalyste et le traitement de la douleur / El psicoanalista en el tratamiento del dolor

A dor se manifesta como mal-estar do corpo e no corpo, e tende a ser encaminhada para tratamento médico. O objetivo deste trabalho é analisar a queixa dolorosa do ponto de vista do tratamento psicanalítico, retomando algumas acepções relacionadas ao tratamento da dor, encontradas na obra de Freud. Partimos da experiência no trabalho em hospital pediátrico, utilizando a análise do atendimento de pacientes com queixas de dor para definir e situar a dor no campo da psicanálise, e distingui-la do campo da medicina. No texto, pode-se acompanhar a dor como signo de sofrimento e diversas formas de abordá-la tanto pelo sujeito que a porta quanto pelas instituições que propõem seu cuidado.

Pain is expressed can be described as physical discomfort and is usually treated medically. In this article we analyze complaints of pain from a psychoanalytic perspective, taking into account several Freudian concepts. We base the article on experiences in a pediatric hospital, related to the treatment of patients with complaints of pain, in order to define and situate pain in the psychoanalytic field and distinguish it from the field of medicine. In the text, pain can be seen as a sign of suffering, and there are various ways to treat it, both from the point of view of the person who feels it and from that of the institutions that propose to treat it.

La douleur se manifeste comme mal physique et par le physique et on a tendance à recourir au traitement médical pour s'en affranchir. L'objectif de ce travail est d'analyser la plainte de la douleur du point de vue du traitement psychanalytique en reprenant quelques acceptions sur le traitement de la douleur dans l'œuvre de Freud. Nous prenons comme point de départ le travail dans un hôpital pédiatrique et en analysons les plaintes de douleur pour définir et situer la douleur au domaine de la psychanalyse et la distinguer du domaine de la médicine. La douleur peut donc être interprétée comme signe de souffrance et nous disposons de plusieurs façons de la traiter, non seulement par le sujet, mais aussi par les institutions qui en prennent compte.

El dolor se manifiesta como malestar del cuerpo y en el cuerpo y, tiende a ser derivado para un tratamiento médico. El objetivo de este trabajo es analizar la queja de dolor desde el punto de vista del tratamiento psicoanalítico, retomando algunos conceptos referidos al tratamiento del dolor presentes en la obra de Freud. Partimos de la experiencia del trabajo en hospital pediátrico, usando el análisis del tratamiento a pacientes que se quejan de dolor para definir y situar el dolor en el campo del psicoanálisis, distinguiéndolo del campo de la medicina. En el texto se puede acompañar el entendimiento del dolor como una señal de sufrimiento y las diversas formas de abordarlo, tanto por el sujeto que lo sufre como por las instituciones que proponen su cuidado.

Mutação do fator V de Leiden em paciente com síndrome de Down: relato de caso / Mutation in factor V Leiden in patients with Down syndrome: case report

JUSTIFICATIVA E OBJETIVOS: A mutação no fator V de Leiden é a anormalidade genética predisponente mais comum para tromboembolismo venoso (TEV). Sua forma heterozigótica é encontrada em 5% da população e a forma homozigótica em 1% da população. A alta prevalência da doença de Leiden na população em geral correlacionada com níveis relativamente baixos de TEV sugere que a mutação produz um risco moderadamente aumentado de trombose, e que existe combinação com outros fatores de risco, dentre eles, o uso de anticoncepcional oral (ACO). Pouco se conhece sobre o risco de TEV em pacientes com síndrome de Down (SD). O objetivo deste estudo foi relatar o caso de paciente portadora de SD, fazendo uso de ACO, que apresentou acidente vascular encefálico isquêmico (AVEi) e trombose venosa profunda (TVP), bem como realizar uma revisão bibliográfica sobre os eventos tromboembólicos acometendo os portadores de SD. RELATO DO CASO: Paciente do sexo feminino, 17 anos, portadora de SD, em tratamento com levotiroxina sódica, obesa, após um ano do início de ACO apresentou quadro compatível com AVEi, e dois dias após, TVP de membro inferior esquerdo,sendo diagnosticada com mutação do fator V de Leiden. CONCLUSÃO: Devido à maior incidência de obesidade, sedentarismo e hipotireoidismo nos pacientes com SD, pode-se considerar que o uso de ACO venha a ser um fator adicional para a ocorrência de eventos tromboembólicos nestes pacientes. No entanto, até o momento não há dados que apontem maior prevalência de mutação do fator V de Leiden nos portadores de SD. Propõem-se novos estudos clínicos para avaliar os distúrbios da hemostasia nos pacientes com SD.

BACKGROUND AND OBJECTIVES: The most common clotting abnormality associated with venous thromboembolism is a reduced inactivation of coagulation factor V. This abnormality has a prevalence of 1% to 7% in the general population and 20% to 30% of patients with thrombosis. The high prevalence of the mutation in factor V in the general population, correlated with relatively low levels of venous thromboembolism suggests that the mutation produces a moderately increased risk of thrombosis, and there is a combination with other risk factors such as the use of oral contraceptives (OCA). The risk of venous thromboembolism (VTE) in patients with Down syndrome (DS) isn't well known, and the benefit on using OCA in this population it is questionable. The objective is describing the case of a patient with DS who had an ischemic stroke and deep vein thrombosis. CASE REPORT: Female patient, 17 years-old, with DS, 17 years old, treated with levothyroxine, obese, one year after the start of OCA presented clinically compatible with ischemic stroke, and two days later, deep vein thrombosis in left lower limb. After laboratory tests, was diagnosed with mutation of factor V Leiden. CONCLUSION: Due to a higher incidence of obesity, sedentary lifestyle and hypothyroidism in patients with DS, we can consider that the use of OCA will be an additional factor for the occurrence of thromboembolic events in these patients. We propose the evaluation of coagulation tests and research for congenital disorders of hemostasis in patients with DS before the beginning of OCA use.

Pharmacogenetic typing for oral anti-coagulant response among factor V Leiden mutation carriers.

Context: Factor V Leiden mutation is the most common inherited predisposition for hypercoagulability and thereby a common genetic cause for initiation of oral anti-coagulation therapy. There is a dearth of knowledge of coumarin response profile in such thrombophilic population. Aims: The current pilot study aims to estimate coumarin sensitivity in an Indian cohort with an inherited thrombophilia risk factor (Factor V Leiden mutation carriers) based on the observed frequency of CYP2C9 *2, *3 and VKORC1-1639G >A genotype combinations. Settings and Design: A retrospective study carried out in a tertiary health care center in India. Materials and Methods: Carriers of FVL mutation were genotyped for CYP2C9 (*2, *3) and VKORC1 (-1639G >A) variants by PCR-RFLP technique. Statistical Analysis Used: Chi-square test to analyze difference in expected and observed genotype frequency. Results: Sixty-one (n = 61) unrelated carriers of FVL mutation were observed in the 13 years study period. The allele frequency of CYP2C9 *2, CYP2C9 *3, and VKORC1-1639A in this cohort was 0.06, 0.11, and 0.16, respectively. Six (9.7%) individuals had two of the three variant alleles (heterozygous or homozygous), and 28 (45.9%) were heterozygous for at least one polymorphism. Conclusions: Pre-prescription genotyping for coumarin drugs, if introduced in Indians with inherited thrombophilia (in whom oral anti-coagulant therapy may be necessary), is likely to identify 9.7% (hypersensitive) subjects in whom the optimum anti-coagulation may be achieved with reduced dosages, 44.3% (normal sensitivity) who may require higher dose and also 55.6% (hyper and moderate sensitivity) subjects who are likely to experience bleeding episodes.

Sob a sombra do patológico: sujeito e verdade no adoecer / Beneath the shadow of the pathological: subject and truth in getting sick / Sous l'ombre du pathologique: sujet et vérité dans le devenir malade / Bajo la sombra de lo patológico: sujeto y verdad en el adolecer

Este artigo analisa fontes da tradição da medicina da alma que tratam do adoecer. Inspirado em Georges Canguilhem, examina-se a noção de saúde e doença anterior às especializações modernas de modo a ressaltar que o adoecimento e as paixões que o acompanham são consequências da condição de vivente. Conclui-se que a antiga definição do humano como sujeito ao padecimento guarda semelhanças com o sujeito patológico concebido pela atual Psicopatologia Fundamental.

This article analyzes primary sources from the tradition of "medicine of the soul," which deals with the experience of getting sick. Inspired by Georges Canguilhem, the notions of health and disease that were available before the development of modern specializations are examined in order to show that falling ill and the emotions related to this process are actually consequences of being alive. The author concludes that the ancient definition of human as vulnerable to suffering has close similarities with the pathological subject, which is conceived in today's field of fundamental psychopathology.

Cet article analyse des sources de la médecine de l'âme qui traitent de l'expérience de la maladie. Inspiré par Georges Canguilhem, on examine les notions de santé et de maladie antérieures aux spécialisations modernes d'une façon a montrer qu'être malade et les passions de l'âme qui s'en suivent ne sont que des conséquences d'être vivant. On conclue que l'ancienne définition de l'homme comme sujet aux souffrances garde des similarités importantes avec le sujet pathologique de la Psychopathologie fondamentale.

Este artículo analiza las fuentes de la tradición de la medicina del alma que tratan del adolecer. Inspirado en Georges Canguilhem, se examina la noción de salud y de enfermedad anterior a las especialidades modernas de manera a resaltar que el adolecer y las pasiones que lo acompañan son consecuencias de la condición de estar vivo. Se concluye que la definición antigua de lo humano como sujeto del padecimiento guarda semejanzas con el sujeto patológico concebido por la actual Sicopatología Fundamental.

Thrombophilic molecular markers in young patients (<40 years) with coronary artery disease.

Background: There has been an alarming rise in the incidence of coronary artery disease (CAD) in India especially involving the age group of less than 45 years. In recent past, various studies focused on hemostatic aspects of CAD, but could not determine the significance of thrombophilic molecular marker in combination. The study was undertaken to investigate the association of thrombophilia related molecular markers in young patients with CAD. Materials and Methods: Thirty diagnosed patients with CAD of either sex under 40 years were included. Thirty healthy age and sex matched control subjects without evidence of CAD formed the control group. Detailed history and clinical examination findings were recorded. In addition to routine investigations, polymerase chain reaction (PCR) based molecular analysis for Factor V Leiden (FVL), methyltetrahydrofolate reductase (MTHFR) gene, tumor necrosis factor receptor 2 (TNFR2) gene, and prothrombin gene mutation were carried out. Results: The mean age (± SD) was 36.86 ± 3.90 years in the patients. Smoking was the most prevalent risk factor. FVL, MTHFR and TNFR2 gene mutation were seen in nine (30%) patient. Three patients had presence of more than one mutation. FVL, MTHFR and TNFR2 gene mutation was found in 4 (13.3%), 3 (10%), and 5 (16.6%) patients respectively. Prothrombin gene mutation was not seen in any of the subjects. There was no significant difference in lipid profile, fibrinogen levels and CRP among the patients with mutation and patients without mutation. Conclusion: Almost one-third of the cases were positive for the various mutations in the study and the presence of at-least one or the other risk factor adds on to the risk of future thrombosis. There is a need to demonstrate or document these mutations in a larger group further based upon ethnicity and geographic distribution.