quinta-feira, 30 de setembro de 2010

Brasil o voto feminino e a eleição de uma presidenta




O Brasil deve ter orgulho de suas mulheres, suas lutas e suas conquistas.

Em momentos de eleições, ter candidatas mulheres disputando a presidência é uma glória para esse país.

É hora também de refletirmos nossa historia e nosso progresso como nação democrática desde de 1946, quando as mulheres tiveram direito a votar.

Desde então as mulheres merecidamente e por competência estão ocupando cargos e responsabilidades em órgāos públicos e privados.

O Brasil vem mudando e para melhor ao longo desses 64 anos com a participação das mulheres na vida pública.

Chegou a hora de eleger uma mulher para presidenta do Brasil.

Na foto acima - Alzira Soriano prefeita de Lages (RN) em 1928

As restrições ao pleno exercício do voto feminino só foram eliminadas no Código Eleitoral de 1934. No entanto, o código não tornava obrigatório o voto feminino. Apenas o masculino. O voto feminino, sem restrições, só passou a ser obrigatório em 1946

O direito ao voto feminino começou pelo Rio Grande do Norte. Em 1927, o Estado se tornou o primeiro do país a permitir que as mulheres votassem nas eleições.

Naquele mesmo ano, a professora Celina Guimarães --de Mossoró (RN) se tornou a primeira brasileira a fazer o alistamento eleitoral. A conquista regional desse direito beneficiou a luta feminina da expansão do "voto de saias" para todo o país.

Mulheres no poder

A primeira mulher escolhida para ocupar um cargo eletivo é do Rio Grande do Norte. Foi Alzira Soriano, eleita prefeita de Lajes, em 1928, pelo Partido Republicano. Mas ela não terminou o seu mandato. A Comissão de Poderes do Senado anulou os votos de todas as mulheres.

Carlota Pereira de Queiroz foi eleita deputada federal em 1933
Em 3 de maio de 1933, a médica paulista Carlota Pereira de Queiroz foi a primeira mulher a votar e ser eleita deputada federal. Ela participou dos trabalhos na Assembléia Nacional Constituinte, entre 1934 e 1935.

A primeira mulher a ocupar um lugar no Senado foi Eunice Michiles (PDS-AM), em 1979. Suplente, ela assumiu o posto com a morte do titular do cargo, o senador João Bosco de Lima. As primeiras mulheres eleitas senadoras, em 1990, foram Júnia Marise (PRN-MG) e Marluce Pinto (PTB-RR). Suplente de Fernando Henrique Cardoso, Eva Blay (PSDB-SP) assumiu o mandato dele quando o tucano se tornou ministro do ex-presidente Itamar Franco.

Em 1994, Roseana Sarney (pelo então PFL) foi a primeira mulher a ser eleita governadora, no Maranhão. Em 1996, o Congresso Nacional instituiu o sistema de cotas na Legislação Eleitoral --que obrigava os partidos a inscreverem, no mínimo, 20% de mulheres nas chapas proporcionais. No ano seguinte, o sistema foi revisado e o mínimo passou a ser de 30%.

A primeira mulher ministra de Estado foi Maria Esther Figueiredo Ferraz (Educação), em 1982. Hoje, as mulheres não só estão à frente de vários ministérios como há uma Secretaria Especial de Políticas para as Mulheres --chefiada por Nilcéa Freire, que tem status de ministra.

Apesar do avanço feminino na política, o Brasil ainda não teve nenhuma mulher eleita presidente. Entre as ministras do presidente Luiz Inácio Lula da Silva está Dilma Rousseff (Casa Civil), cotada como possível candidata do PT à Presidência da República, em 2010. Outra ministra, Marta Suplicy (Turismo) é a favorita dentro do PT para disputar a Prefeitura de São Paulo nas eleições de outubro de 2008. Seu nome também é cotado para a eleição para o governo de São Paulo, em 2010.

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quarta-feira, 29 de setembro de 2010

Muitos Doutores pouca inovação




Por Thiago Romero, da Assessoria de Imprensa da SBPC

Brasil forma 12 mil doutores por ano e taxa de empregabilidade é de 75%, mas esses profissionais ainda não estão gerando inovação tecnológica enquanto negócio nas empresas.

O Brasil vem construindo um dos sistemas mais robustos de Educação Superior e de Ciência e Tecnologia (C&T) do mundo, mas ainda não está conseguindo apropriar-se amplamente desta conquista. Isso por conta de um grande descompasso entre a baixa capacidade de inovação das empresas e a alta competência científica das universidades brasileiras, mensurada pela crescente formação de alunos de pós-graduação, especialmente doutores.

O cenário foi apresentado na conferência "Mercado de Trabalho Para Recém-Doutores", proferida por José Oswaldo Siqueira, do Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq), na manhã desta terça-feira (28/9), na Reunião Regional da SBPC em Lavras (MG).

O docente da Universidade Federal de Lavras (Ufla), que falou sobre o papel das universidades no desenvolvimento tecnológico nacional, explicou que a pesquisa acadêmica contribui com novas descobertas, teóricas ou empíricas, mas raramente gera invenções específicas.

Atualmente no Brasil, explicou, é alta a demanda por doutores no mercado de trabalho.

"Formamos, por ano, quase 12 mil doutores no Brasil e publicamos cerca de 40 mil artigos em revistas especializadas. A taxa de empregabilidade desses doutores é da ordem de 75%, sendo que os setores público e o da educação são os principais empregadores. Temos um mercado potencial para os doutores no país, mas eles ainda não estão fazendo pesquisa e desenvolvimento (P&D) que gere inovação tecnológica enquanto negócio nas empresas", apontou.

Siqueira divulgou um levantamento que mostra uma realidade inversa. De uma amostra de 3 mil empresas situadas no Vale do Silício, nos Estados Unidos, apenas 20 utilizaram tecnologias obtidas na academia, mais especificamente na Universidade de Stanford. "Em linhas gerais, apenas 10% dos novos produtos ou processos introduzidos pelas empresas americanas têm contribuição imediata de pesquisas acadêmicas", disse.

Os países desenvolvidos formam entre 30 e 45 mil doutores por ano e a grande parte é empregada no setor privado. Nos Estados Unidos, cerca de 90% das inovações nascem nas empresas a partir de investimentos próprios em P&D.

"A grande questão é que a maioria dos pós-graduandos brasileiros ainda dá preferência por carreiras nas universidades. A formação de tantos doutores e as altas taxas de empregabilidade no Brasil ainda não resultam em inovação porque esses profissionais ainda não estão nas empresas. Somente 8,4% dos grupos de pesquisa do CNPq relatam relacionamento com empresas", afirmou.

Além da falta de interesse dos recém-doutores, Siqueira apontou outras três causas da baixa quantidade de doutores nas empresas brasileiras: fraca visão estratégica para pesquisa e desenvolvimento (P&D) dos empresários, perfil de formação acadêmica dos doutores é muito restrito e custo elevado para contratação desses profissionais.
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terça-feira, 28 de setembro de 2010

Tb of not Tb

Nós estamos onde estávamos antes da descobeertas das drogas para tuberculose. The Scientist entrevista Bill Jacobs do Albert Einstein College
sobre tuberculose.



- By Erica Westly
TB or not TB?

Mycobacterium tuberculosis
Bill Jacobs’s laboratory at the Albert Einstein College of Medicine in the Bronx sits in front of what was once a 500-bed tuberculosis sanitarium. For Jacobs, the now-decrepit facility serves as both a reminder of the past and a warning of what could happen if effective weapons against a wave of new drug-resistant strains of TB aren’t developed soon. “We’re basically back to where we were before drugs,” he says.

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Jacobs, 54, has been in the TB field for more than 20 years. Although he started his academic career as a mathematics major, today he is known as the grandfather of tuberculosis genetics. “Before him, Mycobacterium tuberculosis genetics was a totally intractable problem,” says Christopher Sassetti, a bacterial genetics researcher at the University of Massachusetts, Amherst. “Most of the work was focused on trying to understand the cell biology of the pathogen.” Today, Jacobs, a Howard Hughes Medical Institute investigator, runs one of the largest, most technologically advanced TB labs in the world.

Walking into Jacobs’s biosafety level-3 lab for the first time is a little unnerving. As we pile on item after item of safety gear—shower caps, masks, gloves, and thick plastic suits that cover even our shoes—Jacobs repeatedly assures me how safe the lab is, saying I have a better chance of contracting TB on the subway (not exactly a comforting thought for someone who regularly takes public transportation).

“We’re basically back to where we were before drugs.”
Inside the lab’s steel doors, a group of researchers shoots a training video while another conducts cell culture experiments. In the animal room, the most protected area of the lab, a one-of-a-kind apparatus that Jacobs helped design infects mice with TB through a series of pumps, then transfers the cages through the wall into a culture hood in the next room so no one has to handle them directly. The technology allows Jacobs’s staff to work with strains of extensively drug-resistant TB that most other labs in the field wouldn’t touch.

One of the most exciting discoveries to come out of Jacobs’s lab in the past few years came from a former postdoc. Rainer Kalscheuer, now at Heinrich-Heine University in Germany, was searching for genes and proteins that made some TB cells more treatment tolerant than others. After doing a microarray analysis, Kalscheuer wanted to investigate a metabolic intermediate enzyme called GlgE, but Jacobs balked. “I told him a group at Harvard had already shown that glgE was an essential gene that can’t be manipulated,” Jacobs remembers. But Kalscheuer persevered and found out that glgE could be knocked out and studied if grown in the right culture medium.

The insight would lead Kalscheuer and Jacobs in an unexpected, but fruitful, direction.

The key to creating viable glgE knockout strains turned out to be trehalose, a cell wall carbohydrate. TB bacteria that lacked glgE died instantly when trehalose was present, but survived if it was removed. The Harvard group had used medium that contained trehalose without realizing it because the carbohydrate, used as a preservative, was an unlisted ingredient.

The next step for Kalscheuer and Jacobs was figuring out the functional relationship between the two proteins. GlgE had been implicated in glycogen metabolism, but the connection with trehalose was unclear. Finally, after a painstaking series of suppressor genetics experiments, they elucidated the biochemical pathway: Glycogen and glucose produce trehalose; an enzyme known as trehalose synthase converts the trehalose into maltose; then, the maltose becomes maltose-1-phosphate, the protein that GlgE converts into glucan. When glgE is knocked out, maltose-1-phosphate accumulates, which kills the tuberculosis bacterium.

Now that Jacobs knows how glgE mutations can kill TB, he is trying to find a drug company willing to work on a project to exploit the bacterial weakness. “The GlgE gene is a great potential drug target because there’s no human homologue,” which means TB cells would be affected without harming human cells, Jacobs explains.

Back in his office, Jacobs shows me photographs from one of his first visits to South Africa where the incidence of drug-resistant TB is particularly high. All of the patients were housed together in a crowded ward, with nothing separating them from the hospital staff. “That was the only time I was ever scared of getting infected,” he recalls. Today, Jacobs has several collaborators in South Africa and is helping to build a state-of-the-art TB research facility there. The goal is to get more African researchers using the latest diagnostic technologies, but equally important, Jacobs says, is encouraging new drug development. “One drug is not enough,” he says. “Our collaborators in Africa say they need at least three new TB drugs.”

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segunda-feira, 27 de setembro de 2010

Os fichas-suja na Bahia




ELEIÇÕES 2010: Bahia tem 12 candidatos fichas-suja concorrendo as eleições 2010
segunda-feira, 27 de setembro de 2010
Leia abaixo a lista dos candidatos da Bahia que foram barrados pela Lei da Ficha Limpa, são réus em ações penais, foram denunciados como integrantes do esquema dos sanguessugas ou foram presos em operações das polícias Civil e Federal:

1- Coriolano Sales (PSDB) - candidato a deputado federal (deferido, com recurso). Foi um dos deputados denunciados pela CPI dos Sanguessugas. Responde ao processo 9789-73.2010.4.01.3600 na Justiça Federal de Mato Grosso pelos crimes de quadrilha ou bando, corrupção passiva e lavagem de dinheiro. Para evitar o processo de cassação, renunciou ao mandato em 15 de agosto de 2006. Por causa da renúncia, teve sua candidatura impugnada pelo TRE-BA com base na Lei da Ficha Limpa. Mantém-se candidato graças a recurso.
"O ex-deputado foi acusado de receber propina equivalente a 10% do valor das emendas que beneficiariam a máfia das ambulâncias. Ainda de acordo com a denúncia, Coriolano fazia contato com as prefeituras para combinar o andamento dos processos de licitação submetidos a fraude. O ex-parlamentar renunciou ao mandato sob a acusação de ter recebido R$ 172,4 mil em propina para direcionar licitações em municípios baianos em favor da Planam. Ele foi o primeiro deputado a renunciar para escapar da cassação. Procurado pela reportagem, Coriolano negou ter qualquer contato com a família Vedoin e a máfia das ambulâncias. Ele disse que renunciou ao mandato porque esperava assumir a prefeitura de Vitória da Conquista (BA), com a cassação do mandato do prefeito daquele município. “Precisava me afastar daquele rolo.” O candidato diz ter sofrido sérios prejuízos políticos com a denúncia, segundo ele, jamais provada. “Pago essa conta até hoje”, declarou."

2- Dilson Batista Santiago (PT)- candidato a deputado estadual - barrado com base na Lei da Ficha Limpa

3- Edson Luiz Ramos Dantas (PSB)- candidato a deputado federal - barrado com base na Lei da Ficha Limpa

4- Itamar da Silva Rios (PTB) – candidato a deputado estadual - barrado com base na Lei da Ficha Limpa

5- Jadiel Almeida Mascarenhas (PRB) – candidato a deputado estadual - barrado com base na Lei da Ficha Limpa

6- Jaldo Batista Souza (PRTB) – candidato a deputado estadual - barrado com base na Lei da Ficha Limpa

7- Jonival Lucas Junior (PTB) - candidato a deputado federal - Foi um dos deputados denunciados pela CPI dos Sanguessugas. Responde ao processo 13226-30.2007.4.01.3600 na Justiça Federal de Mato Grosso pelos crimes de quadrilha ou bando, corrupção passiva e lavagem de dinheiro.
"O ex-deputado foi acusado de receber comissão de R$ 7,3 mil em troca de emenda que favoreceria a “máfia dos sanguessugas”. O empresário Luiz Antônio Vedoin disse que o valor só foi acertado após a apresentação da emenda. Na defesa apresentada à Câmara, Jonival Lucas declarou que jamais intermediou licitação em municípios. Ele também afirmou desconhecer que um assessor de seu gabinete tivesse recebido dinheiro do esquema. O ex-deputado incluiu na defesa transcrição do depoimento do ex-assessor, em que ele admitia ter recebido dinheiro sem conhecimento do parlamentar. O ex-funcionário afirmou, ainda, que se negou a intermediar a negociação da licitação por não ter autonomia para tal e que não chegou a sacar o valor transferido. O ex-parlamentar ainda incluiu depoimento do ex-prefeito do município beneficiado por sua emenda, que o isentava de qualquer responsabilidade nas licitações da prefeitura."

8 - Maurício Trindade (PR) – candidato a deputado federal – réu na Ação Penal 510 (tráfico de influência. Data de autuação: 28/04/2009)

9- Osmar Rodrigues Torres (PTdoB) – candidato a deputado estadual - barrado com base na Lei da Ficha Limpa

10- Raimundo Caires Rocha (PMDB) – candidato a deputado estadual - barrado com base na Lei da Ficha Limpa

11 - Robério Nunes (DEM) - candidato a deputado estadual - Foi um dos deputados denunciados pela CPI dos Sanguessugas. Responde ao processo 15231-88.2008.4.01.3600 na Justiça Federal de Mato Grosso pelos crimes de quadrilha ou bando, corrupção passiva e contra a Lei de Licitações.
"O ex-deputado foi acusado de ter recebido 10% do valor de emendas apresentadas por ele na área da saúde. De acordo com o empresário Luiz Antônio Vedoin, um depósito de R$ 10 mil foi feito na conta de uma pessoa a pedido de Robério Nunes. O empresário afirmou, ainda, ter repassado R$ 15 mil, em espécie, ao então deputado em seu gabinete. Segundo a denúncia, o ex-parlamentar se comprometeu a “acertar detalhes” do direcionamento das licitações nos municípios para os quais fez emenda. Na defesa apresentada à Câmara, Robério disse ser vítima de “acusações falsas” de Vedoin. "Todos foram jogados na vala comum – os que tinham contra si provas cabais e aqueles contra os quais havia somente indícios ou mera suspeita", criticou o ex-deputado na defesa entregue ao Conselho de Ética. O ex-parlamentar afirmou nunca ter recebido vantagem indevida, seja diretamente ou por meio de assessores, em troca de emendas."

12- Roberto Britto (PP) – dep.federal – réu na Ação Penal 512 (corrupção eleitoral).Data de autuação: 29/04/2009

Fonte: Congresso em Foco

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Os fichas sujas na Bahia




-ELEIÇÕES 2010: Bahia tem 12 candidatos fichas-suja concorrendo as eleições 2010
segunda-feira, 27 de setembro de 2010
Leia abaixo a lista dos candidatos da Bahia que foram barrados pela Lei da Ficha Limpa, são réus em ações penais, foram denunciados como integrantes do esquema dos sanguessugas ou foram presos em operações das polícias Civil e Federal:

1- Coriolano Sales (PSDB) - candidato a deputado federal (deferido, com recurso). Foi um dos deputados denunciados pela CPI dos Sanguessugas. Responde ao processo 9789-73.2010.4.01.3600 na Justiça Federal de Mato Grosso pelos crimes de quadrilha ou bando, corrupção passiva e lavagem de dinheiro. Para evitar o processo de cassação, renunciou ao mandato em 15 de agosto de 2006. Por causa da renúncia, teve sua candidatura impugnada pelo TRE-BA com base na Lei da Ficha Limpa. Mantém-se candidato graças a recurso.
"O ex-deputado foi acusado de receber propina equivalente a 10% do valor das emendas que beneficiariam a máfia das ambulâncias. Ainda de acordo com a denúncia, Coriolano fazia contato com as prefeituras para combinar o andamento dos processos de licitação submetidos a fraude. O ex-parlamentar renunciou ao mandato sob a acusação de ter recebido R$ 172,4 mil em propina para direcionar licitações em municípios baianos em favor da Planam. Ele foi o primeiro deputado a renunciar para escapar da cassação. Procurado pela reportagem, Coriolano negou ter qualquer contato com a família Vedoin e a máfia das ambulâncias. Ele disse que renunciou ao mandato porque esperava assumir a prefeitura de Vitória da Conquista (BA), com a cassação do mandato do prefeito daquele município. “Precisava me afastar daquele rolo.” O candidato diz ter sofrido sérios prejuízos políticos com a denúncia, segundo ele, jamais provada. “Pago essa conta até hoje”, declarou."

2- Dilson Batista Santiago (PT)- candidato a deputado estadual - barrado com base na Lei da Ficha Limpa

3- Edson Luiz Ramos Dantas (PSB)- candidato a deputado federal - barrado com base na Lei da Ficha Limpa

4- Itamar da Silva Rios (PTB) – candidato a deputado estadual - barrado com base na Lei da Ficha Limpa

5- Jadiel Almeida Mascarenhas (PRB) – candidato a deputado estadual - barrado com base na Lei da Ficha Limpa

6- Jaldo Batista Souza (PRTB) – candidato a deputado estadual - barrado com base na Lei da Ficha Limpa

7- Jonival Lucas Junior (PTB) - candidato a deputado federal - Foi um dos deputados denunciados pela CPI dos Sanguessugas. Responde ao processo 13226-30.2007.4.01.3600 na Justiça Federal de Mato Grosso pelos crimes de quadrilha ou bando, corrupção passiva e lavagem de dinheiro.
"O ex-deputado foi acusado de receber comissão de R$ 7,3 mil em troca de emenda que favoreceria a “máfia dos sanguessugas”. O empresário Luiz Antônio Vedoin disse que o valor só foi acertado após a apresentação da emenda. Na defesa apresentada à Câmara, Jonival Lucas declarou que jamais intermediou licitação em municípios. Ele também afirmou desconhecer que um assessor de seu gabinete tivesse recebido dinheiro do esquema. O ex-deputado incluiu na defesa transcrição do depoimento do ex-assessor, em que ele admitia ter recebido dinheiro sem conhecimento do parlamentar. O ex-funcionário afirmou, ainda, que se negou a intermediar a negociação da licitação por não ter autonomia para tal e que não chegou a sacar o valor transferido. O ex-parlamentar ainda incluiu depoimento do ex-prefeito do município beneficiado por sua emenda, que o isentava de qualquer responsabilidade nas licitações da prefeitura."

8 - Maurício Trindade (PR) – candidato a deputado federal – réu na Ação Penal 510 (tráfico de influência. Data de autuação: 28/04/2009)

9- Osmar Rodrigues Torres (PTdoB) – candidato a deputado estadual - barrado com base na Lei da Ficha Limpa

10- Raimundo Caires Rocha (PMDB) – candidato a deputado estadual - barrado com base na Lei da Ficha Limpa

11 - Robério Nunes (DEM) - candidato a deputado estadual - Foi um dos deputados denunciados pela CPI dos Sanguessugas. Responde ao processo 15231-88.2008.4.01.3600 na Justiça Federal de Mato Grosso pelos crimes de quadrilha ou bando, corrupção passiva e contra a Lei de Licitações.
"O ex-deputado foi acusado de ter recebido 10% do valor de emendas apresentadas por ele na área da saúde. De acordo com o empresário Luiz Antônio Vedoin, um depósito de R$ 10 mil foi feito na conta de uma pessoa a pedido de Robério Nunes. O empresário afirmou, ainda, ter repassado R$ 15 mil, em espécie, ao então deputado em seu gabinete. Segundo a denúncia, o ex-parlamentar se comprometeu a “acertar detalhes” do direcionamento das licitações nos municípios para os quais fez emenda. Na defesa apresentada à Câmara, Robério disse ser vítima de “acusações falsas” de Vedoin. "Todos foram jogados na vala comum – os que tinham contra si provas cabais e aqueles contra os quais havia somente indícios ou mera suspeita", criticou o ex-deputado na defesa entregue ao Conselho de Ética. O ex-parlamentar afirmou nunca ter recebido vantagem indevida, seja diretamente ou por meio de assessores, em troca de emendas."

12- Roberto Britto (PP) – dep.federal – réu na Ação Penal 512 (corrupção eleitoral).Data de autuação: 29/04/2009

Fonte: Congresso em Foco


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Penicilina, a maior descoberta Século XX

A penicilina foi a maior descoberta do século XX. Com isolamento desse antibiótico só aplicado para seres humanos em 1942. Veja a história completa da descoberta publicada no The Scientist


-By Cristina Luiggi
The Discovery of Penicillin, circa 1928
It was the wonder drug of the 20th century: A yellow liquid that seeps from the spores of the Penicillium fungal mold and contains a compound that shatters the cell walls of bacteria responsible for common diseases such as pneumonia, strep throat, scarlet fever, syphilis, and meningitis. With steep reductions in human mortality rates and drastic improvements in quality of life, penicillin may very well be one of mankind’s greatest discoveries.

Scottish doctor Alexander Fleming observed the mold killing his Staphylococcus cultures in late 1928 while working at St. Mary’s Hospital in London. But by the start of World War II, no one had figured out how to efficiently extract the active ingredient from Penicillium, whose concentration “is almost the same as gold in sea water,” says Robert Bud, Principal Curator of Medicine at The Science Museum in London and author of Penicillin: Triumph and Tragedy.
It wasn’t until the end of 1940 that doctors at Oxford University had collected enough penicillin to treat one person: a policeman who got blood poisoning from a small scratch on his face. Unfortunately, his intravenous treatment of penicillin used up the entire stock of the drug. Doctors tried recycling penicillin from his urine to continue his treatment, Bud says, but with barely one hundredth of a gram of antibiotic per gallon of urine, it simply wasn’t enough. The man died shortly after the penicillin ran out



In 1942, the Russians held the record for treating the most patients with the drug, Bud says, scraping the Penicillium off the walls of damp air raid shelters and rubbing the fungal juice directly onto affected areas. Two years later, researchers finally succeeded in mass-producing the antibiotic by growing a mutant Penicillium strain in corn starch liquor in large metal tanks—just in time to aid the thousands of soldiers who would be wounded on the beaches of Normandy on D-Day.
The wonder drug has lost some of its killer properties in the decades following its initial widespread use, with hospitals reporting penicillin-resistant infections as early as the mid-1940s. A new antibiotic called methicillin initially served as a good alternative, but bacteria have since evolved ways to circumvent methicillin’s deadly grip as well. Methicillin-resistant Staphylococcus aureus (MRSA) was responsible for around 20,000 deaths in the United States in 2005.

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domingo, 26 de setembro de 2010

Diversidade de monócitos




Neste artigo da Immunity este artigo revela algumas diferenças em
Monócitos e suas implicações para a resposta inflamatória.



Diversity: A Hallmark of Monocyte Society
Summary

Murine inflammatory and patrolling monocytes have specific functional specializations. In this issue of Immunity, Cros et al., 2010 characterize CD14+ and CD14dimCD16+ monocyte subpopulations as the human inflammatory and patrolling monocytes that, similarly to their mouse counterparts, are characterized by distinct functional properties.

Acesse artigo completo

http://download.cell.com/immunity/pdf/PIIS1074761310003304.pdf?intermediate=true


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sábado, 25 de setembro de 2010

Pergunte ao seu orientador




Pergunte ao seu orientador

Orientadores são seres incompreensíveis às vezes. Todo pós-graduando com certeza já teve vontade de fazer algumas “perguntinhas” ao seu orientador. Se você nunca teve coragem de fazer essas perguntas mais… sinceras, a sua oportunidade chegou!
Pergunte ao nosso Orientador que ele responde.
P: O senhor não acha que tenho traduzido artigos em inglês demais?
R: Verdade. Mas não se preocupe. Assim que você acabar esses, tenho alguns em alemão e outros em japonês na minha gaveta.

P: Por que o senhor deixa pra corrigir todos os meus relatórios, projetos e artigos na última hora?
R: Você precisa ver a cara de desespero que você faz. Acho hilário.

P: Como que eu vou dar conta de estudar tudo isso que o senhor pediu?
R: O que é mesmo que você faz da meia-noite às seis?

P: O senhor já se esqueceu que um dia foi estagiário também?
R: Já. Próxima.

P: O senhor não acha que trata seus orientados como escravos?
R: Não. Eu não mando, eu peço. E quando você não faz o que eu peço, não te dou chibatadas. Apenas corto a sua bolsa. Viu só como é muito diferente?

P: Existe alguma previsão se eu terei pelo menos um final de semana livre?
R: Claro que sim! Assim que você entregar sua monografia encadernada na biblioteca.
Envie a sua pergunta para o @posgraduando ou no contato@posgraduando.com. Mas não tenha muita pressa. Afinal de contas, sabe como é orientador, né?
Aviso aos estressadinhos: o conteúdo deste post é de caráter irônico-sarcástico-humorístico. Releve.



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quinta-feira, 23 de setembro de 2010

Host–microbe interaction: Inflammation for growth




Infection often leads to inflammatory immune responses; no surprises there. It has long been speculated, however, that the ability to induce intestinal inflammatory responses favours pathogen growth. Most hypotheses on how this might occur have centred on nutrient release through tissue damage or on the intestinal epithelial cells secreting macromolecules, such as extracellular matrix proteins, that can be used as nutrient sources. But the underlying molecular mechanisms of inflammation-induced nutrient availability for pathogens have remained largely elusive. In a remarkable paper on page 426 of this issue, Winter et al. connect the production by the mammalian host of reactive oxygen species — as part of the inflammatory response to the pathogenic bacterium Salmonella enterica serotype Typhimurium — to a unique, metabolic pathway in the pathogen that allows it to compete with the resident gut microbiota.


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Location:Brasil

quarta-feira, 22 de setembro de 2010

Inflamaçāo ajuda patógeno no intestino






Host–microbe interaction: Inflammation for growth - Nature
SAMUEL I. MILLER
Infection often leads to inflammatory immune responses; no surprises there. It has long been speculated, however, that the ability to induce intestinal inflammatory responses favours pathogen growth. Most hypotheses on how this might occur have centred on nutrient release through tissue damage or on the intestinal epithelial cells secreting macromolecules, such as extracellular matrix proteins, that can be used as nutrient sources. But the underlying molecular mechanisms of inflammation-induced nutrient availability for pathogens have remained largely elusive. In a remarkable paper on page 426 of this issue, Winter et al. connect the production by the mammalian host of reactive oxygen species — as part of the inflammatory response to the pathogenic bacterium Salmonella enterica serotype Typhimurium — to a unique, metabolic pathway in the pathogen that allows it to compete with the resident gut microbiota.

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domingo, 19 de setembro de 2010

Piadas de médicos




O sujeito vai ao hospital, caindo de bêbado. Durante a consulta, vêm as perguntas de praxe:
- Nome?
- Juvenal dos Santos!
- Idade?
- 32 anos.
- O senhor bebe?
- Vou aceitar um gole, mas só pra te acompanhar!


Tirei ou nao?
O médico olha pra cara do paciente e pergunta:
-Eu já não tirei as suas amígdalas?
- Não...
- Não tirei seu apêndice?
- Não, doutor...
- Você não tinha uma namorada chamada Cássia?
- Tinha sim, doutor...
- Eu sabia que tinha tirado alguma coisa de você.


Auto-demissão
Numa entrevista para emprego, o empregador pergunta ao candidato:
-Vejo que seu último emprego foi com um psiquiatra. Por que deixou o cargo?
-Bem, não havia escapatória pra mim - responde o candidato. - Se eu chegasse tarde no trabalho, eu era hostil. Se chegasse antes da hora, sofria de ansiedade e, se chegasse na hora, era compulsivo


Diferenças Entre as Especialidades Médicas

Sabem qual a diferença entre um clínico, um cirurgião-geral, um psiquiatra e um patologista?
O clínico: Sabe tudo e não resolve nada.
O cirurgião: Não sabe nada mas resolve tudo.
O psiquiatra: Não sabe nada e não resolve nada.
O patologista: Sabe tudo, resolve tudo, mas sempre chega atrasado.


Exame de prostata

O homem vai fazer exame de próstata e leva junto uma faca. Chegando lá, o médico logo pergunta:
- Por que a faca?
Ele responde:
- Porque. . . Se eu gostar, me mate!


Um Certo Homem Entra em Um. . .
Um certo homem entra em um consultório médico e pergunta:
- Doutor será que posso viver até os 100 anos?
O médico começa o questionamento.
Você fuma?
Não.
Bebe?
Nem uma gota.
Vivem fazendo sexo noite a dentro?
De forma alguma doutor.
- Meu amigo, você quer viver até os 100 anos pra que?


O Cara Chega no Laboratorio. . .
O cara chega no laboratorio para pegar o exame da esposa:
- Eu vim buscar o exame de Maria da Silva.
A atendente:
- Que bom que o senhor apareceu, nós estavamos mesmo preocupados, só que o senhor não deixou telefone. É o seguinte, nós fizemos uma confusão e misturamos o exame de sua esposa com o de outra Maria da Silva. Só que um deu positivo para Aids e o outro para Alzheimer.
E o cara:
- Nossa! E agora, o que eu faço!
- O doutor recomenda que o senhor leve sua esposa para bem longe de casa e a abandone. . . Se ela voltar, nunca mais faça amor com ela!

Caso clinico - patológico para diagnóstico NEJM











CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL

Case 28-2010 — A 32-Year-Old Woman, 3 Weeks Post Partum, with Substernal Chest Pain

Presentation of Case

Dr. Rebecca R. Saff (Medicine): A 32-year-old woman, 3 weeks post partum, was seen in the emergency department of this hospital because of substernal chest pain.

The patient had been well until the day of admission when, while she was shopping at 7:25 p.m., pain in the left jaw and substernal area developed suddenly. She drove home and called emergency medical services (EMS). During evaluation by EMS personnel, oxygen was administered; her symptoms resolved after a duration of approximately 20 minutes. She declined further treatment, and the emergency responders departed. Shortly thereafter, the pain recurred, associated with shortness of breath. The patient called EMS again.

On repeat evaluation at 8:34 p.m., the patient rated the pain at 5 (on a scale of 0 to 10, where 10 is the most severe pain) and stated that at its onset, the pain rated a score of 7. The blood pressure was 148/74 mm Hg. An electrocardiogram (ECG) reportedly showed a normal sinus rhythm, with a rate from 90 to 100 beats per minute, and ST-segment elevation of up to 4 mm in leads V3 through V6. Oxygen, acetylsalicylic acid, nitroglycerin, and morphine were administered. The pain resolved while the patient was in the ambulance; a repeat ECG showed ST-segment elevations (1 to 4 mm) in leads V1 through V6; hyperacute T waves in leads V4, V5, and V6; and ST-segment depressions (1 to 1.5 mm) in the inferior leads (Figure 1 in the Supplementary Appendix, available with the full text of this article at NEJM.org). The patient was brought to the emergency department at this hospital 1 hour 25 minutes after the initial onset of symptoms.

The patient did not have diaphoresis, nausea, vomiting, dyspnea, pain or swelling in the legs, or back pain. Three weeks earlier, she had had an uncomplicated, spontaneous vaginal delivery at 39 weeks of gestation. During the first trimester of pregnancy, her systolic blood pressures ranged from 120 to 140 mm Hg, and her diastolic blood pressures from 60 to 80 mm Hg; in the second trimester, 118 to 120 mm Hg systolic and 60 to 82 mm Hg diastolic; and in the third trimester, 104 to 130 mm Hg systolic and 60 to 78 mm Hg diastolic. No antihypertensive medications had been given. The placenta weighed 340 g (less than the 5th percentile in size for gestational age); pathological examination revealed an increased amount of perivillous fibrin. Her child was healthy and was breast-feeding. During her first pregnancy, the patient had hypertension, with onset before 20 weeks of gestation, followed by preeclamptic toxemia that was treated with magnesium sulfate. Between pregnancies, her blood pressure was normal and she took no medications. At the 10-day postpartum visit, she felt well and was ambulating; the blood pressure was 120/80 mm Hg. She lived with her husband and her toddler and newborn and was a physician. She did not smoke, drink alcohol, or use illicit drugs. Her parents had had hypertension and hypercholesterolemia, and a distant cousin had had a stroke at a young age. The patient was taking no medications and had no allergies.

On examination, the temperature was 36.2°C, the blood pressure 143/92 mm Hg in the left arm and 137/81 mm Hg in the right arm, the pulse 83 to 92 beats per minute without ectopy, the respiratory rate 20 breaths per minute, and the oxygen saturation 95% while the patient was breathing ambient air and 100% while she was breathing oxygen (2 liters by nasal cannula). The carotid pulses were 2+ bilaterally, without bruits, and the jugular veins were distended at 6 to 7 cm. The remainder of the examination was normal. ECG revealed a sinus rhythm, 89 beats per minute, with normal intervals; possible left atrial enlargement; incomplete right bundle-branch block; and ST-segment elevation of 1 mm in leads V2 and V3 (Figure 2 in the Supplementary Appendix). Testing for troponin I was negative. The D-dimer level was 1166 ng per milliliter (reference range, <500), and the amylase level was 134 U per liter (reference range, 3 to 100); other tests, including a complete blood count, measurement of electrolyte and glucose levels, and tests of renal and liver function, were normal. A chest radiograph obtained in the emergency department was normal.

While in the emergency department, the patient continued to have episodes of substernal chest pain lasting approximately 5 minutes. Between episodes, the ST-segment changes seen on the ECG resolved completely (Figure 3 in the Supplementary Appendix).

A diagnostic procedure was performed.

Differential Diagnosis

Dr. Marc S. Sabatine: I cared for this patient and am aware of the diagnosis. I would like to ask her to tell us about her symptoms.

The Patient: I was well and was out shopping with my toddler. When I picked him up, I felt transiently ill, possibly nausea, followed by intense pain in my left jaw and by intense, very sharp substernal chest pain, which continued to get worse. I had never experienced anything like this before. I left the store and went home, thinking it would get better. I wasn't thinking about a heart attack.

Dr. Sabatine: Eventually, you were concerned enough to call EMS. What was going through your mind?

The Patient: When I got home, I told my husband to call 911 right away because the pain was so bad. Initially, I thought it might be very severe heartburn. I also considered a pulmonary embolism, because I was post partum. Suddenly, the pain resolved, so I concluded it was not a pulmonary embolism.

Dr. Sabatine: By the time EMS personnel arrived, you were feeling better and you sent them away. They came back a second time and obtained an ECG. Did they show you the ECG?

The Patient: I saw it from about 2 feet away. I could see the changes, and they were shocking to me. At that point, I was happy we were on our way to the hospital.

Dr. Sabatine: The patient's chief symptom, chest pain, is common. Chest pain accounts for approximately 7 million visits per year to an emergency department in the United States.

Causes of Chest Pain

The differential diagnosis of chest pain is well rehearsed and includes cardiovascular, pulmonary, gastrointestinal, and musculoskeletal causes. For a 32-year-old woman, cardiovascular causes would normally be unlikely. However, since the patient was 3 weeks post partum, several potential cardiovascular causes deserve special attention. First, the risk of acute myocardial infarction during pregnancy or the postpartum period is increased by a factor of 3 or 4 as compared with age-matched female control subjects, although the absolute rate remains low at approximately 6 per 100,000 pregnancies.1 Second, pregnancy is considered to be a risk factor for aortic dissection.2 In a 1944 report of an autopsy series, half of the women younger than 40 years of age who had an aortic dissection were pregnant.3 However, rigorous epidemiologic data supporting such an association are lacking.4 Third, the risk of pulmonary embolism during the postpartum period is increased by a factor of 3 or 4 as compared with age-matched female control subjects,5 although the absolute incidence is only 40 per 100,000 pregnancies.

The patient's ECG showed ST-segment elevation in a coronary distribution that, although not pathognomonic, in the context of chest pain strongly suggests acute myocardial infarction. Coronary atherosclerosis is the underlying cause of myocardial infarction in more than 90% of cases. However, in this case, one needs to give serious consideration to events other than rupture of a coronary atherosclerotic plaque as the cause of myocardial infarction (Table 1).

Table 1


Nonatherosclerotic Causes of Myocardial Infarction.

Among postpartum women who present with myocardial infarction and undergo coronary angiography, coronary dissection accounts for approximately 35% of cases, stenosis approximately 30%, thrombus approximately 15%, and spasm less than 5%; normal coronary arteries are found in approximately 10% of cases.6 This categorization is probably imperfect, with unrecognized dissections being classified as stenoses or thrombus and transient spasm being classified as thrombus or normal. Thus, coronary-artery dissection is a likely diagnosis in this case.

Coronary-Artery Dissection

Coronary-artery dissections comprise two main categories: dissections that are secondary to mechanical precipitation, and those that are spontaneous (Table 2). Spontaneous coronary dissection, the most likely diagnosis in this case, is rare14,15; it is noted in approximately 0.2% of coronary angiographies performed16 and in up to 3.5% of coronary angiographies with intravascular ultrasonography performed for acute coronary syndromes.17 The mean age at occurrence is 42 years; nearly three fourths of patients are women, and 30% of the women are peripartum, as was our patient.15

Table 2


Causes of Coronary-Artery Dissection.

Patients with spontaneous coronary dissections can be divided into four subgroups (Table 2). The first group includes patients with preexisting arteritis or an inherited disorder of connective tissue,8–13 in which the integrity of the arterial wall has been compromised by inflammation or defective structural proteins. The second group includes patients with atherosclerosis; almost all these patients are men, with a mean age of 55 years and almost always with involvement of the right coronary artery.18,19 It has been postulated that the rupture of an atherosclerotic plaque creates an intimal disruption that allows a dissection to occur, and that shorter delays to angiography and the availability of newer diagnostic tools such as intravascular ultrasonography have allowed recognition of a ruptured plaque in a greater proportion of patients than had been appreciated previously (up to 80% in one series).17

The third group includes women who are peripartum; three fourths of the cases in this group occur from 1 day to 3 months post partum, with the majority occurring within the first 2 weeks.20 Of the cases of spontaneous coronary-artery dissection that occur during pregnancy, the majority occur in the last 4 weeks. Advancing age and multiparity are risk factors, with the mean age being 33 years and the typical parity 2 or 3. Cases of spontaneous dissection have also been reported under circumstances that involve altered estrogen or progesterone levels, including oral contraceptive use,21,22 menstruation,22–24 and hepatic cirrhosis.25 In contrast to the patients who have underlying atherosclerosis, 87% of peripartum coronary dissections involve the left coronary tree and 40% involve multiple coronary arteries, with one third involving both the left and the right coronary arteries.

The final group is idiopathic spontaneous coronary-artery dissection. The average age is 41 years, and three fourths of the patients are women, almost all of whom are premenopausal and without traditional cardiac risk factors.18,26,27 Some patients are involved in activities that would increase coronary shear stress, including some that would be expected to greatly influence hemodynamics (severe systolic hypertension, cocaine use, snow shoveling, weight lifting)28–32 and others that seem relatively benign (running, aerobics, sneezing).33–35 The onset of chest pain in this patient occurred after she picked up her toddler. One might speculate that the patients involved in the relatively benign activities had an underlying, unappreciated predisposition. More than 80% of idiopathic dissections involve the left coronary tree.

Clinical Presentation and Diagnosis of Spontaneous Coronary-Artery Dissection

The clinical presentation depends on the location and severity of coronary involvement and the resultant severity of the compromise in myocardial blood flow and oxygen supply. The majority of patients present with myocardial infarction with ST-segment elevation, as our patient did, but myocardial infarction without ST-segment elevation, unstable angina, and stable angina have been reported. As with any acute coronary syndrome, patients can present with hemodynamic or arrhythmic complications, including cardiogenic shock and sudden cardiac death, the latter of which may lead to underreporting of the incidence of coronary dissection. Tamponade can develop from adventitial rupture of the dissection.36

Coronary angiography is the diagnostic test of choice. The dissection typically involves the proximal segment of the coronary artery. Angiography may reveal an intimal flap, but if there is no visible flow into the false lumen or if the dissection develops as a consequence of an intramural hematoma, angiography may reveal only a simulated coronary stenosis due to compression of the true lumen.37 Disruption of the vasa vasorum may be a cause of the intramural hemorrhage.30 Intravascular ultrasonography can reveal the dissection in these situations.38 Multidetector-row computed tomographic angiography has also been used to identify and noninvasively track the resolution of a coronary dissection.39

In this case, coronary angiography was performed.

Dr. Marc S. Sabatine's Diagnosis

Postpartum coronary-artery dissection.

Diagnostic Procedure

Dr. Farouc A. Jaffer: I met the patient in the emergency department. We recommended urgent coronary angiography, with the leading considerations of postpartum coronary-artery dissection, coronary arterial vasospasm, and coronary atherosclerosis.

Cardiac catheterization through a femoral artery was performed at approximately 9 p.m., shortly after the patient's arrival at the emergency room. Multiple angiographic projections showed a 35-mm-long segment of severe narrowing (90% stenosis) in the middle of the left anterior descending coronary artery (Figure 1), with a smooth contour that was consistent with intramural hematoma, distal haziness that was consistent with a dissection site, and minimal vascular disease in other coronary arteries that was consistent with the presence of coronary-artery dissection (Video 1, available at NEJM.org). According to the Thrombolysis in Myocardial Infarction (TIMI) criteria for coronary-artery flow, the blood flow in the left anterior descending artery was grade 2 (on a scale of 0 to 3, where 0 is no flow and 3 is normal flow).

Figure 1


Coronary Angiogram on Presentation.

Our diagnosis was postpartum coronary-artery dissection.

Discussion of Management

Dr. Sabatine: Treatment decisions for coronary-artery dissection are largely empirical. As patients typically present with an acute coronary syndrome, treatment with aspirin and heparin is often initiated before the diagnosis is known. In contrast to aortic dissections, for which anticoagulation is avoided to reduce the risk of expansion of the false lumen, for coronary dissections a critical concern is maintaining patency of the true lumen. To that end, short-term use of a glycoprotein IIb/IIIa inhibitor has been reported,40 as has long-term treatment with aspirin and clopidogrel41 and aspirin and enoxaparin42; although the patients did well in these cases, whether the interventions were beneficial remains undetermined.

Fibrinolytic therapy has been used as part of the standard empirical pharmacologic therapy for myocardial infarction with ST-segment elevation. In the case of coronary-artery dissection, the fibrinolytic agent could lyse a thrombus in the true lumen, restoring patency, and could lyse a thrombus in the false lumen, relieving compression of the true lumen, and thus reestablish antegrade flow.43 However, fibrinolysis also runs the risk of precipitating increased flow into the false lumen and propagating the dissection. Clinical deterioration after the use of intravenous fibrinolytic therapy can occur,44 as can an angiographic extension of the dissection after the use of intracoronary fibrinolytic therapy.33 Thus, if coronary dissection is high on the differential diagnosis, empirical fibrinolytic therapy should be avoided if possible.

Antiischemic therapy with beta-blockers and nitrates is frequently initiated, with the latter potentially also helping reduce the risk of superimposed vasospasm. For that reason, calcium-channel blockers are sometimes used in addition to or instead of beta-blockers.

Reperfusion therapy is mandated if the patient has ongoing symptoms of myocardial ischemia, compromised coronary flow, or inducible ischemia on stress testing. Percutaneous coronary intervention with stenting has become the treatment of choice,45 although it carries additional risk in patients with coronary-artery dissection, particularly involving passage of the guidewire down the false lumen and extension of the dissection.46 In cases in which an intimal tear is visualized, a stent can be placed at the entry site and, without further inflow, the false lumen can become obliterated over time.47 In the absence of an intimal tear, stenting of the entire length of the dissection has been performed to prevent expansion of the intramural hematoma.48 Intravascular ultrasonography can be used to guide the intervention by confirming true and false lumina and to confirm sealing of the dissection, adequate compression of the intramural hematoma, or both.38

Coronary-artery bypass grafting (CABG) is typically reserved for patients with persistent ischemia in whom the location or extent of disease precludes percutaneous coronary intervention.

Dr. Eric S. Rosenberg (Pathology): Dr. Jaffer, can you tell us how you managed the patient's condition?

Dr. Jaffer: Our therapeutic options consisted of supportive management with medical therapy with or without an intraaortic balloon pump, percutaneous coronary intervention (PCI), and CABG surgery. The patient was pain free and the ST-segment elevation had resolved. Since coronary dissections may heal without mechanical intervention, and in view of the risk of entering the false lumen during PCI, we elected supportive therapy.

An intraaortic balloon pump was placed to augment coronary arterial blood flow in the left anterior descending artery. In addition, we administered an anticoagulant agent (heparin) and an antiplatelet agent (aspirin), as well as beta-blockers and statins, based on American College of Cardiology–American Heart Association guidelines for acute coronary syndrome. I favored initiation of statins because of the likely presence of intramural hematoma in the coronary vessel wall. As shown by preclinical and autopsy investigations, red cells in the arterial wall may stimulate atherogenesis by means of the deposition of free cholesterol, inducing macrophage infiltration.49 We did not administer glycoprotein IIb/IIIa antagonists, since we were concerned that if the dissection worsened, the patient could need emergency cardiac surgery. Cardiac biomarkers later indicated the presence of a small myocardial infarction. Cardiac ultrasonography showed an ejection fraction of 75%, without wall-motion abnormalities. An angiotensin-converting–enzyme inhibitor was initiated, but hypotension developed and it was discontinued.

After 48 hours, a second coronary angiogram (Video 2, available at NEJM.org) showed improved blood flow (TIMI grade 3), a shorter segment of stenosis of the left anterior descending artery (approximately 25 mm), and resolution of the distal dissection flap. These findings indicated favorable healing of the coronary-artery dissection. The intraaortic balloon pump was discontinued. Since surgery was unlikely to be required, clopidogrel was administered according to ACS guidelines. In addition, we elected to initiate warfarin to provide maximal anticoagulation on an outpatient basis, with the goal of averting thrombosis of the left anterior descending artery. The patient recovered well and was discharged on hospital day 8, taking warfarin, clopidogrel, atenolol, simvastatin, and aspirin. We planned to discontinue clopidogrel after 1 year and recommended aspirin indefinitely.

Dr. Sabatine: I would like to ask Dr. Staats and Dr. Stone to discuss the pathological features of the placenta and of the heart in this and other cases.

Pathological Discussion

Dr. Paul N. Staats: The placenta was small for the gestational age, with a fresh weight of 340 g after removal of the fetal membranes and umbilical cord, as compared with a mean of 540 g and a 10th percentile of 430 g for a gestational age of 39 weeks.50 It was otherwise grossly normal. Histologic examination revealed a slightly greater deposition of perivillous fibrin (Figure 2A) than normal and rare foci of accelerated branching of villi near the maternal floor, characterized by small terminal villi with sclerosis, increased numbers of prominent syncytial knots, and fewer intermediate-size villi than normal, with a concomitant increase in the amount of intervillous space (Figure 2B). Although a similar pattern is frequently seen beneath the fetal surface of normal placentas, the presence of this pattern near the maternal floor suggests placental ischemia.51,52 Pregnancy-induced hypertension and preeclampsia are believed to be caused by abnormal conversion of maternal vasculature during implantation. The resulting poor perfusion and ischemia cause the placental findings.53 Placental ischemia due to maternal hypertension is generally seen with chronic or poorly controlled hypertension and preterm pre-eclampsia.52 The most common finding is a small placenta (less than the 10th percentile by weight), as seen in this case. Placental infarcts are more common and more extensive in cases of maternal hypertension than in women with normal placentas. Rather than the pyramid-shaped infarcts involving the basal plate (maternal floor) that are often seen at term because of senescence, the infarcts associated with maternal hypertension are often smaller, intraparenchymal, and rounded, suggesting watershed ischemia.52 We did not see such infarcts in this case. Decidual vasculopathy is the most characteristic finding in placentas with clinically significant maternal hypertension, but it is seen only infrequently and was not present in this case.51,52 The accelerated branching of villi seen in this case is apparent in placental ischemia from any cause and is thought to be an adaptive response to the ischemia.51

Figure 2


Placental Histology.

The final pathological diagnosis in this case was a small, mature placenta (340 g) with mildly increased perivillous fibrin deposition and focal accelerated villous branching. Although the findings are nonspecific, they are consistent with placental ischemia due to maternal hypertension.

Dr. Nancy Lee Harris (Pathology): Dr. Sabatine, do you think that hypertension during pregnancy contributed to this dissection?

Dr. Sabatine: Hypertension is a risk factor for peripartum myocardial infarction due to atherosclerosis. Acute, severe systolic hypertension has been associated with coronary-artery dissection. Gestational hypertension has not been noted to be particularly frequent among cases of peripartum coronary-artery dissection.

Dr. Rosenberg: Dr. Stone, can you tell us about the pathology of coronary-artery dissection?

Dr. James R. Stone: The pathology of spontaneous coronary-artery dissection has largely been deduced from autopsy cases, although a few explanted hearts from patients undergoing cardiac transplantation have been studied (Figure 3A).26,54 The dissection typically occurs in the outer portion of the medial layer, resulting in an intramural hematoma that compresses the true lumen. The cause is not well understood. Most often an intimal tear is not present in pathologic specimens.26,55 In some cases, an adventitial or periadventitial inflammatory infiltrate, most often containing predominantly eosinophils, has been reported,55 but this is most likely a response to and not the cause of the dissection. Severe medial degeneration typical of connective tissue disorders and true necrotizing vasculitis are typically not present. In patients who survive the initial spontaneous coronary-artery dissection, the dissection channel will organize, in some cases resulting in a coronary artery with a double lumen (Figure 3B).

Figure 3


Pathologic Features of Spontaneous Coronary-Artery Dissection in Another Patient.

Prognosis of Coronary-Artery Dissection

Dr. Sabatine: Angiographic resolution of the dissection typically occurs after several months,18 but some dissections progress,56 and pseudoaneurysms can form at the site of the dissection.57 Several cases have been reported of coronary dissections developing at separate sites several months after the index presentation.58 Some data suggest a mortality rate of 5 to 10% in the acute phase16,18,19,27 and a rate approaching 0% among peripartum patients who survive the acute phase and subsequently undergo angiography.20

Dr. Jaffer: The patient did well, without angina, dyspnea, or evidence of congestive heart failure. We initially deferred her enrollment into cardiac rehabilitation because of concern that exercise could increase coronary wall stress and extend her dissection. We suggested a moderate level of activity. A follow-up coronary angiogram obtained 3 months after her initial presentation, after the discontinuation of warfarin, showed nearly complete resolution of the dissection, minimal irregularities in the left anterior descending artery at the site of the dissection, and normal left ventricular function (Video 3, available at NEJM.org). She subsequently completed a cardiac rehabilitation program. I would like to invite the patient to tell us how she is doing now.

The Patient: I have gone back to work and regular activity without any problems. I feel great.

Dr. Rosenberg: Would you recommend that the patient avoid a future pregnancy?

Dr. Jaffer: Recurrences of coronary-artery dissection have been documented in the literature. For future pregnancies, we would request consultation with the maternal–fetal medicine division for additional guidance.

Anatomical Diagnosis

Postpartum coronary-artery dissection.

Dr. Staats is now affiliated with the Department of Pathology, University of Maryland School of Medicine, Baltimore.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

This case was presented at the Medical Case Conference, June 12, 2009.

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M Maeder, P Ammann, W Angehrn, H RickliIdiopathic spontaneous coronary artery dissection: incidence, diagnosis and treatment.Int J Cardiol2005;101:363-369
BD Jaffe, TM Broderick, CV LeierCocaine-induced coronary-artery dissection.N Engl J Med1994;330:510-511
T Kurum, M AktozSpontaneous coronary artery dissection after heavy lifting in a 25-year-old man with coronary risk factors.J Cardiovasc Med (Hagerstown)2006;7:68-70
RM Nalbandian, JL ChasonIntramural (intramedial) dissecting hematomas in normal or otherwise unremarkable coronary arteries: a “rare” cause of death.Am J Clin Pathol1965;43:348-356
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A Iyisoy, MT Agac, T Celik, B JataSpontaneous dissection of left main coronary artery associated with hypertensive crisis: a probable fatal complication detected by intravascular ultrasound.Int J Cardiol2010;139:e5-e7
WA Almahmeed, M Haykowski, J Boone, Spontaneous coronary artery dissection in young women.Cathet Cardiovasc Diagn1996;37:201-205
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DG Claudon, DB Claudon, JE EdwardsPrimary dissecting aneurysm of coronary artery: a cause of acute myocardial ischemia.Circulation1972;45:259-266
JR Arnold, NE West, WJ van Gaal, TD Karamitsos, AP BanningThe role of intravascular ultrasound in the management of spontaneous coronary artery dissection.Cardiovasc Ultrasound2008;6:24-24
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S Cheung, V Mithani, RM WatsonHealing of spontaneous coronary dissection in the context of glycoprotein IIB/IIIA inhibitor therapy: a case report.Catheter Cardiovasc Interv2000;51:95-100
JW Choi, CJ DavidsonSpontaneous multivessel coronary artery dissection in a long-distance runner successfully treated with oral antiplatelet therapy.J Invasive Cardiol2002;14:675-678
R Sarmento-Leite, PR Machado, SL GarciaSpontaneous coronary artery dissection: stent it or wait for healing?Heart2003;89:164-164
JL Vacek, TL McKiernanIntracoronary streptokinase for acute coronary-artery dissection.N Engl J Med1984;310:1187-1187
EM Buys, MJ Suttorp, WJ Morshuis, HW PlokkerExtension of a spontaneous coronary artery dissection due to thrombolytic therapy.Cathet Cardiovasc Diagn1994;33:157-160
MK Hong, LF Satler, GS Mintz, Treatment of spontaneous coronary artery dissection with intracoronary stenting.Am Heart J1996;132:200-202
JI Gonzalez, JA Hill, CR ContiSpontaneous coronary artery dissection treated with percutaneous transluminal angioplasty.Am J Cardiol1989;63:885-886
MW Klutstein, D Tzivoni, D Bitran, B Mendzelevski, M Ilan, Y AlmagorTreatment of spontaneous coronary artery dissection: report of three cases.Cathet Cardiovasc Diagn1997;40:372-376
PR Vale, DW BaronCoronary artery stenting for spontaneous coronary artery dissection: a case report and review of the literature.Cathet Cardiovasc Diagn1998;45:280-286
FD Kolodgie, HK Gold, AP Burke, Intraplaque hemorrhage and progression of coronary atheroma.N Engl J Med2003;349:2316-2325
H Pinar, CJ Sung, CE Oyer, DB SingerReference values for singleton and twin placental weights.Pediatr Pathol Lab Med1996;16:901-907
RW Redline, T Boyd, V Campbell, Maternal vascular underperfusion: nosology and reproducibility of placental reaction patterns.Pediatr Dev Pathol2004;7:237-249
DJ Roberts, MD PostThe placenta in pre-eclampsia and intrauterine growth restriction.J Clin Pathol2008;61:1254-1260
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Source Information

From the Division of Cardiovascular Medicine, Brigham and Women's Hospital (M.S.S.); the Division of Cardiology, Department of Medicine (M.S.S., F.A.J.), and the Department of Pathology (P.N.S., J.R.S.), Massachusetts General Hospital; and the Departments of Medicine (M.S.S., F.A.J.) and Pathology (P.N.S., J.R.S.), Harvard Medical School — all in Boston.



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sábado, 18 de setembro de 2010

Case 28-2010 — A 32-Year-Old Woman, 3 Weeks Post Partum, with Substernal Chest Pain




Presentation of Case

Dr. Rebecca R. Saff (Medicine): A 32-year-old woman, 3 weeks post partum, was seen in the emergency department of this hospital because of substernal chest pain.

The patient had been well until the day of admission when, while she was shopping at 7:25 p.m., pain in the left jaw and substernal area developed suddenly. She drove home and called emergency medical services (EMS). During evaluation by EMS personnel, oxygen was administered; her symptoms resolved after a duration of approximately 20 minutes. She declined further treatment, and the emergency responders departed. Shortly thereafter, the pain recurred, associated with shortness of breath. The patient called EMS again.

On repeat evaluation at 8:34 p.m., the patient rated the pain at 5 (on a scale of 0 to 10, where 10 is the most severe pain) and stated that at its onset, the pain rated a score of 7. The blood pressure was 148/74 mm Hg. An electrocardiogram (ECG) reportedly showed a normal sinus rhythm, with a rate from 90 to 100 beats per minute, and ST-segment elevation of up to 4 mm in leads V3 through V6. Oxygen, acetylsalicylic acid, nitroglycerin, and morphine were administered. The pain resolved while the patient was in the ambulance; a repeat ECG showed ST-segment elevations (1 to 4 mm) in leads V1 through V6; hyperacute T waves in leads V4, V5, and V6; and ST-segment depressions (1 to 1.5 mm) in the inferior leads (Figure 1 in the Supplementary Appendix, available with the full text of this article at NEJM.org). The patient was brought to the emergency department at this hospital 1 hour 25 minutes after the initial onset of symptoms.

The patient did not have diaphoresis, nausea, vomiting, dyspnea, pain or swelling in the legs, or back pain. Three weeks earlier, she had had an uncomplicated, spontaneous vaginal delivery at 39 weeks of gestation. During the first trimester of pregnancy, her systolic blood pressures ranged from 120 to 140 mm Hg, and her diastolic blood pressures from 60 to 80 mm Hg; in the second trimester, 118 to 120 mm Hg systolic and 60 to 82 mm Hg diastolic; and in the third trimester, 104 to 130 mm Hg systolic and 60 to 78 mm Hg diastolic. No antihypertensive medications had been given. The placenta weighed 340 g (less than the 5th percentile in size for gestational age); pathological examination revealed an increased amount of perivillous fibrin. Her child was healthy and was breast-feeding. During her first pregnancy, the patient had hypertension, with onset before 20 weeks of gestation, followed by preeclamptic toxemia that was treated with magnesium sulfate. Between pregnancies, her blood pressure was normal and she took no medications. At the 10-day postpartum visit, she felt well and was ambulating; the blood pressure was 120/80 mm Hg. She lived with her husband and her toddler and newborn and was a physician. She did not smoke, drink alcohol, or use illicit drugs. Her parents had had hypertension and hypercholesterolemia, and a distant cousin had had a stroke at a young age. The patient was taking no medications and had no allergies.

On examination, the temperature was 36.2°C, the blood pressure 143/92 mm Hg in the left arm and 137/81 mm Hg in the right arm, the pulse 83 to 92 beats per minute without ectopy, the respiratory rate 20 breaths per minute, and the oxygen saturation 95% while the patient was breathing ambient air and 100% while she was breathing oxygen (2 liters by nasal cannula). The carotid pulses were 2+ bilaterally, without bruits, and the jugular veins were distended at 6 to 7 cm. The remainder of the examination was normal. ECG revealed a sinus rhythm, 89 beats per minute, with normal intervals; possible left atrial enlargement; incomplete right bundle-branch block; and ST-segment elevation of 1 mm in leads V2 and V3 (Figure 2 in the Supplementary Appendix). Testing for troponin I was negative. The D-dimer level was 1166 ng per milliliter (reference range, <500), and the amylase level was 134 U per liter (reference range, 3 to 100); other tests, including a complete blood count, measurement of electrolyte and glucose levels, and tests of renal and liver function, were normal. A chest radiograph obtained in the emergency department was normal.

While in the emergency department, the patient continued to have episodes of substernal chest pain lasting approximately 5 minutes. Between episodes, the ST-segment changes seen on the ECG resolved completely (Figure 3 in the Supplementary Appendix).

A diagnostic procedure was performed.

Differential Diagnosis

Dr. Marc S. Sabatine: I cared for this patient and am aware of the diagnosis. I would like to ask her to tell us about her symptoms.

The Patient: I was well and was out shopping with my toddler. When I picked him up, I felt transiently ill, possibly nausea, followed by intense pain in my left jaw and by intense, very sharp substernal chest pain, which continued to get worse. I had never experienced anything like this before. I left the store and went home, thinking it would get better. I wasn't thinking about a heart attack.

Dr. Sabatine: Eventually, you were concerned enough to call EMS. What was going through your mind?

The Patient: When I got home, I told my husband to call 911 right away because the pain was so bad. Initially, I thought it might be very severe heartburn. I also considered a pulmonary embolism, because I was post partum. Suddenly, the pain resolved, so I concluded it was not a pulmonary embolism.

Dr. Sabatine: By the time EMS personnel arrived, you were feeling better and you sent them away. They came back a second time and obtained an ECG. Did they show you the ECG?

The Patient: I saw it from about 2 feet away. I could see the changes, and they were shocking to me. At that point, I was happy we were on our way to the hospital.

Dr. Sabatine: The patient's chief symptom, chest pain, is common. Chest pain accounts for approximately 7 million visits per year to an emergency department in the United States.

Causes of Chest Pain

The differential diagnosis of chest pain is well rehearsed and includes cardiovascular, pulmonary, gastrointestinal, and musculoskeletal causes. For a 32-year-old woman, cardiovascular causes would normally be unlikely. However, since the patient was 3 weeks post partum, several potential cardiovascular causes deserve special attention. First, the risk of acute myocardial infarction during pregnancy or the postpartum period is increased by a factor of 3 or 4 as compared with age-matched female control subjects, although the absolute rate remains low at approximately 6 per 100,000 pregnancies.1 Second, pregnancy is considered to be a risk factor for aortic dissection.2 In a 1944 report of an autopsy series, half of the women younger than 40 years of age who had an aortic dissection were pregnant.3 However, rigorous epidemiologic data supporting such an association are lacking.4 Third, the risk of pulmonary embolism during the postpartum period is increased by a factor of 3 or 4 as compared with age-matched female control subjects,5 although the absolute incidence is only 40 per 100,000 pregnancies.

The patient's ECG showed ST-segment elevation in a coronary distribution that, although not pathognomonic, in the context of chest pain strongly suggests acute myocardial infarction. Coronary atherosclerosis is the underlying cause of myocardial infarction in more than 90% of cases. However, in this case, one needs to give serious consideration to events other than rupture of a coronary atherosclerotic plaque as the cause of myocardial infarction (Table 1).

Table 1


Nonatherosclerotic Causes of Myocardial Infarction.

Among postpartum women who present with myocardial infarction and undergo coronary angiography, coronary dissection accounts for approximately 35% of cases, stenosis approximately 30%, thrombus approximately 15%, and spasm less than 5%; normal coronary arteries are found in approximately 10% of cases.6 This categorization is probably imperfect, with unrecognized dissections being classified as stenoses or thrombus and transient spasm being classified as thrombus or normal. Thus, coronary-artery dissection is a likely diagnosis in this case.

Coronary-Artery Dissection

Coronary-artery dissections comprise two main categories: dissections that are secondary to mechanical precipitation, and those that are spontaneous (Table 2). Spontaneous coronary dissection, the most likely diagnosis in this case, is rare14,15; it is noted in approximately 0.2% of coronary angiographies performed16 and in up to 3.5% of coronary angiographies with intravascular ultrasonography performed for acute coronary syndromes.17 The mean age at occurrence is 42 years; nearly three fourths of patients are women, and 30% of the women are peripartum, as was our patient.15

Table 2


Causes of Coronary-Artery Dissection.

Patients with spontaneous coronary dissections can be divided into four subgroups (Table 2). The first group includes patients with preexisting arteritis or an inherited disorder of connective tissue,8–13 in which the integrity of the arterial wall has been compromised by inflammation or defective structural proteins. The second group includes patients with atherosclerosis; almost all these patients are men, with a mean age of 55 years and almost always with involvement of the right coronary artery.18,19 It has been postulated that the rupture of an atherosclerotic plaque creates an intimal disruption that allows a dissection to occur, and that shorter delays to angiography and the availability of newer diagnostic tools such as intravascular ultrasonography have allowed recognition of a ruptured plaque in a greater proportion of patients than had been appreciated previously (up to 80% in one series).17

The third group includes women who are peripartum; three fourths of the cases in this group occur from 1 day to 3 months post partum, with the majority occurring within the first 2 weeks.20 Of the cases of spontaneous coronary-artery dissection that occur during pregnancy, the majority occur in the last 4 weeks. Advancing age and multiparity are risk factors, with the mean age being 33 years and the typical parity 2 or 3. Cases of spontaneous dissection have also been reported under circumstances that involve altered estrogen or progesterone levels, including oral contraceptive use,21,22 menstruation,22–24 and hepatic cirrhosis.25 In contrast to the patients who have underlying atherosclerosis, 87% of peripartum coronary dissections involve the left coronary tree and 40% involve multiple coronary arteries, with one third involving both the left and the right coronary arteries.

The final group is idiopathic spontaneous coronary-artery dissection. The average age is 41 years, and three fourths of the patients are women, almost all of whom are premenopausal and without traditional cardiac risk factors.18,26,27 Some patients are involved in activities that would increase coronary shear stress, including some that would be expected to greatly influence hemodynamics (severe systolic hypertension, cocaine use, snow shoveling, weight lifting)28–32 and others that seem relatively benign (running, aerobics, sneezing).33–35 The onset of chest pain in this patient occurred after she picked up her toddler. One might speculate that the patients involved in the relatively benign activities had an underlying, unappreciated predisposition. More than 80% of idiopathic dissections involve the left coronary tree.

Clinical Presentation and Diagnosis of Spontaneous Coronary-Artery Dissection

The clinical presentation depends on the location and severity of coronary involvement and the resultant severity of the compromise in myocardial blood flow and oxygen supply. The majority of patients present with myocardial infarction with ST-segment elevation, as our patient did, but myocardial infarction without ST-segment elevation, unstable angina, and stable angina have been reported. As with any acute coronary syndrome, patients can present with hemodynamic or arrhythmic complications, including cardiogenic shock and sudden cardiac death, the latter of which may lead to underreporting of the incidence of coronary dissection. Tamponade can develop from adventitial rupture of the dissection.36

Coronary angiography is the diagnostic test of choice. The dissection typically involves the proximal segment of the coronary artery. Angiography may reveal an intimal flap, but if there is no visible flow into the false lumen or if the dissection develops as a consequence of an intramural hematoma, angiography may reveal only a simulated coronary stenosis due to compression of the true lumen.37 Disruption of the vasa vasorum may be a cause of the intramural hemorrhage.30 Intravascular ultrasonography can reveal the dissection in these situations.38 Multidetector-row computed tomographic angiography has also been used to identify and noninvasively track the resolution of a coronary dissection.39

In this case, coronary angiography was performed.

Dr. Marc S. Sabatine's Diagnosis

Postpartum coronary-artery dissection.

Diagnostic Procedure

Dr. Farouc A. Jaffer: I met the patient in the emergency department. We recommended urgent coronary angiography, with the leading considerations of postpartum coronary-artery dissection, coronary arterial vasospasm, and coronary atherosclerosis.

Cardiac catheterization through a femoral artery was performed at approximately 9 p.m., shortly after the patient's arrival at the emergency room. Multiple angiographic projections showed a 35-mm-long segment of severe narrowing (90% stenosis) in the middle of the left anterior descending coronary artery (Figure 1), with a smooth contour that was consistent with intramural hematoma, distal haziness that was consistent with a dissection site, and minimal vascular disease in other coronary arteries that was consistent with the presence of coronary-artery dissection (Video 1, available at NEJM.org). According to the Thrombolysis in Myocardial Infarction (TIMI) criteria for coronary-artery flow, the blood flow in the left anterior descending artery was grade 2 (on a scale of 0 to 3, where 0 is no flow and 3 is normal flow).

Figure 1


Coronary Angiogram on Presentation.

Our diagnosis was postpartum coronary-artery dissection.

Discussion of Management

Dr. Sabatine: Treatment decisions for coronary-artery dissection are largely empirical. As patients typically present with an acute coronary syndrome, treatment with aspirin and heparin is often initiated before the diagnosis is known. In contrast to aortic dissections, for which anticoagulation is avoided to reduce the risk of expansion of the false lumen, for coronary dissections a critical concern is maintaining patency of the true lumen. To that end, short-term use of a glycoprotein IIb/IIIa inhibitor has been reported,40 as has long-term treatment with aspirin and clopidogrel41 and aspirin and enoxaparin42; although the patients did well in these cases, whether the interventions were beneficial remains undetermined.

Fibrinolytic therapy has been used as part of the standard empirical pharmacologic therapy for myocardial infarction with ST-segment elevation. In the case of coronary-artery dissection, the fibrinolytic agent could lyse a thrombus in the true lumen, restoring patency, and could lyse a thrombus in the false lumen, relieving compression of the true lumen, and thus reestablish antegrade flow.43 However, fibrinolysis also runs the risk of precipitating increased flow into the false lumen and propagating the dissection. Clinical deterioration after the use of intravenous fibrinolytic therapy can occur,44 as can an angiographic extension of the dissection after the use of intracoronary fibrinolytic therapy.33 Thus, if coronary dissection is high on the differential diagnosis, empirical fibrinolytic therapy should be avoided if possible.

Antiischemic therapy with beta-blockers and nitrates is frequently initiated, with the latter potentially also helping reduce the risk of superimposed vasospasm. For that reason, calcium-channel blockers are sometimes used in addition to or instead of beta-blockers.

Reperfusion therapy is mandated if the patient has ongoing symptoms of myocardial ischemia, compromised coronary flow, or inducible ischemia on stress testing. Percutaneous coronary intervention with stenting has become the treatment of choice,45 although it carries additional risk in patients with coronary-artery dissection, particularly involving passage of the guidewire down the false lumen and extension of the dissection.46 In cases in which an intimal tear is visualized, a stent can be placed at the entry site and, without further inflow, the false lumen can become obliterated over time.47 In the absence of an intimal tear, stenting of the entire length of the dissection has been performed to prevent expansion of the intramural hematoma.48 Intravascular ultrasonography can be used to guide the intervention by confirming true and false lumina and to confirm sealing of the dissection, adequate compression of the intramural hematoma, or both.38

Coronary-artery bypass grafting (CABG) is typically reserved for patients with persistent ischemia in whom the location or extent of disease precludes percutaneous coronary intervention.

Dr. Eric S. Rosenberg (Pathology): Dr. Jaffer, can you tell us how you managed the patient's condition?

Dr. Jaffer: Our therapeutic options consisted of supportive management with medical therapy with or without an intraaortic balloon pump, percutaneous coronary intervention (PCI), and CABG surgery. The patient was pain free and the ST-segment elevation had resolved. Since coronary dissections may heal without mechanical intervention, and in view of the risk of entering the false lumen during PCI, we elected supportive therapy.

An intraaortic balloon pump was placed to augment coronary arterial blood flow in the left anterior descending artery. In addition, we administered an anticoagulant agent (heparin) and an antiplatelet agent (aspirin), as well as beta-blockers and statins, based on American College of Cardiology–American Heart Association guidelines for acute coronary syndrome. I favored initiation of statins because of the likely presence of intramural hematoma in the coronary vessel wall. As shown by preclinical and autopsy investigations, red cells in the arterial wall may stimulate atherogenesis by means of the deposition of free cholesterol, inducing macrophage infiltration.49 We did not administer glycoprotein IIb/IIIa antagonists, since we were concerned that if the dissection worsened, the patient could need emergency cardiac surgery. Cardiac biomarkers later indicated the presence of a small myocardial infarction. Cardiac ultrasonography showed an ejection fraction of 75%, without wall-motion abnormalities. An angiotensin-converting–enzyme inhibitor was initiated, but hypotension developed and it was discontinued.

After 48 hours, a second coronary angiogram (Video 2, available at NEJM.org) showed improved blood flow (TIMI grade 3), a shorter segment of stenosis of the left anterior descending artery (approximately 25 mm), and resolution of the distal dissection flap. These findings indicated favorable healing of the coronary-artery dissection. The intraaortic balloon pump was discontinued. Since surgery was unlikely to be required, clopidogrel was administered according to ACS guidelines. In addition, we elected to initiate warfarin to provide maximal anticoagulation on an outpatient basis, with the goal of averting thrombosis of the left anterior descending artery. The patient recovered well and was discharged on hospital day 8, taking warfarin, clopidogrel, atenolol, simvastatin, and aspirin. We planned to discontinue clopidogrel after 1 year and recommended aspirin indefinitely.

Dr. Sabatine: I would like to ask Dr. Staats and Dr. Stone to discuss the pathological features of the placenta and of the heart in this and other cases.

Pathological Discussion

Dr. Paul N. Staats: The placenta was small for the gestational age, with a fresh weight of 340 g after removal of the fetal membranes and umbilical cord, as compared with a mean of 540 g and a 10th percentile of 430 g for a gestational age of 39 weeks.50 It was otherwise grossly normal. Histologic examination revealed a slightly greater deposition of perivillous fibrin (Figure 2A) than normal and rare foci of accelerated branching of villi near the maternal floor, characterized by small terminal villi with sclerosis, increased numbers of prominent syncytial knots, and fewer intermediate-size villi than normal, with a concomitant increase in the amount of intervillous space (Figure 2B). Although a similar pattern is frequently seen beneath the fetal surface of normal placentas, the presence of this pattern near the maternal floor suggests placental ischemia.51,52 Pregnancy-induced hypertension and preeclampsia are believed to be caused by abnormal conversion of maternal vasculature during implantation. The resulting poor perfusion and ischemia cause the placental findings.53 Placental ischemia due to maternal hypertension is generally seen with chronic or poorly controlled hypertension and preterm pre-eclampsia.52 The most common finding is a small placenta (less than the 10th percentile by weight), as seen in this case. Placental infarcts are more common and more extensive in cases of maternal hypertension than in women with normal placentas. Rather than the pyramid-shaped infarcts involving the basal plate (maternal floor) that are often seen at term because of senescence, the infarcts associated with maternal hypertension are often smaller, intraparenchymal, and rounded, suggesting watershed ischemia.52 We did not see such infarcts in this case. Decidual vasculopathy is the most characteristic finding in placentas with clinically significant maternal hypertension, but it is seen only infrequently and was not present in this case.51,52 The accelerated branching of villi seen in this case is apparent in placental ischemia from any cause and is thought to be an adaptive response to the ischemia.51

Figure 2


Placental Histology.

The final pathological diagnosis in this case was a small, mature placenta (340 g) with mildly increased perivillous fibrin deposition and focal accelerated villous branching. Although the findings are nonspecific, they are consistent with placental ischemia due to maternal hypertension.

Dr. Nancy Lee Harris (Pathology): Dr. Sabatine, do you think that hypertension during pregnancy contributed to this dissection?

Dr. Sabatine: Hypertension is a risk factor for peripartum myocardial infarction due to atherosclerosis. Acute, severe systolic hypertension has been associated with coronary-artery dissection. Gestational hypertension has not been noted to be particularly frequent among cases of peripartum coronary-artery dissection.

Dr. Rosenberg: Dr. Stone, can you tell us about the pathology of coronary-artery dissection?

Dr. James R. Stone: The pathology of spontaneous coronary-artery dissection has largely been deduced from autopsy cases, although a few explanted hearts from patients undergoing cardiac transplantation have been studied (Figure 3A).26,54 The dissection typically occurs in the outer portion of the medial layer, resulting in an intramural hematoma that compresses the true lumen. The cause is not well understood. Most often an intimal tear is not present in pathologic specimens.26,55 In some cases, an adventitial or periadventitial inflammatory infiltrate, most often containing predominantly eosinophils, has been reported,55 but this is most likely a response to and not the cause of the dissection. Severe medial degeneration typical of connective tissue disorders and true necrotizing vasculitis are typically not present. In patients who survive the initial spontaneous coronary-artery dissection, the dissection channel will organize, in some cases resulting in a coronary artery with a double lumen (Figure 3B).

Figure 3


Pathologic Features of Spontaneous Coronary-Artery Dissection in Another Patient.

Prognosis of Coronary-Artery Dissection

Dr. Sabatine: Angiographic resolution of the dissection typically occurs after several months,18 but some dissections progress,56 and pseudoaneurysms can form at the site of the dissection.57 Several cases have been reported of coronary dissections developing at separate sites several months after the index presentation.58 Some data suggest a mortality rate of 5 to 10% in the acute phase16,18,19,27 and a rate approaching 0% among peripartum patients who survive the acute phase and subsequently undergo angiography.20

Dr. Jaffer: The patient did well, without angina, dyspnea, or evidence of congestive heart failure. We initially deferred her enrollment into cardiac rehabilitation because of concern that exercise could increase coronary wall stress and extend her dissection. We suggested a moderate level of activity. A follow-up coronary angiogram obtained 3 months after her initial presentation, after the discontinuation of warfarin, showed nearly complete resolution of the dissection, minimal irregularities in the left anterior descending artery at the site of the dissection, and normal left ventricular function (Video 3, available at NEJM.org). She subsequently completed a cardiac rehabilitation program. I would like to invite the patient to tell us how she is doing now.

The Patient: I have gone back to work and regular activity without any problems. I feel great.

Dr. Rosenberg: Would you recommend that the patient avoid a future pregnancy?

Dr. Jaffer: Recurrences of coronary-artery dissection have been documented in the literature. For future pregnancies, we would request consultation with the maternal–fetal medicine division for additional guidance.

Anatomical Diagnosis

Postpartum coronary-artery dissection.

Dr. Staats is now affiliated with the Department of Pathology, University of Maryland School of Medicine, Baltimore.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

This case was presented at the Medical Case Conference, June 12, 2009.

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Source Information

From the Division of Cardiovascular Medicine, Brigham and Women's Hospital (M.S.S.); the Division of Cardiology, Department of Medicine (M.S.S., F.A.J.), and the Department of Pathology (P.N.S., J.R.S.), Massachusetts General Hospital; and the Departments of Medicine (M.S.S., F.A.J.) and Pathology (P.N.S., J.R.S.), Harvard Medical School — all in Boston.



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