Traductor

03 February 2012

DNA test that identifies Down syndrome in pregnancy can also detect trisomy 18 and trisomy 13

A newly available DNA-based prenatal blood test that can identify a pregnancy with Down syndrome can also identify two additional chromosome abnormalities: trisomy 18 (Edwards syndrome) and trisomy 13 (Patau syndrome).The test for all three defects can be offered as early as 10 weeks of pregnancy to women who have been identified as being at high risk for these abnormalities. These are the results of an international, multicenter study published online February 2 in the journal Genetics in Medicine. The study, the largest and most comprehensive done to date, adds to the documented capability (study published in Genetics in Medicine in October 2011) of the tests by examining results in 62 pregnancies with trisomy 18 and 12 pregnancies with trisomy 13.Together with the Down syndrome pregnancies reported earlier, 286 trisomic pregnancies and 1,702 normal pregnancies are included in the report.
The research was led by Glenn Palomaki, PhD, and Jacob Canick, PhD, of the Division of Medical Screening and Special Testing in the Department of Pathology and Laboratory Medicine at Women & Infants Hospital of Rhode Island and The Warren Alpert Medical School of Brown University, and included scientists at Sequenom Inc. and Sequenom Center for Molecular Medicine, San Diego, CA, and an independent academic laboratory at the University of California at Los Angeles.
The test identified 100% (59/59) of the trisomy 18 and 91.7% (11/12) of the trisomy 13 pregnancies.The associated false positive rates were 0.28 and 0.97%, respectively.Overall, testing failed to provide a clinical interpretation in 17 women (0.9%); three of these women had a trisomy 18 pregnancy.By slightly raising the definition of a positive test for chromosome 18 and 13, the detection rate remained constant, but the false positive rate could be as low as 0.1%.These findings, along with the detailed information learned from testing such a large number of samples, demonstrate that the new test will be highly effective when offered to women considering invasive testing.
"Our previous work demonstrated the ability to identify Down syndrome, the most common trisomy.These new data extend the finding to the next two most common trisomies and will allow for wider use of such testing with the ability to identify all three common trisomies," said Dr. Palomaki."The new DNA test can now also be offered to women identified as being as high risk for trisomy 18 or trisomy 13, as well those at high risk for Down syndrome."
"This highly sensitive and specific DNA test has the potential to impact on couples' decision-making," says Dr. Canick."A woman whose pregnancy was identified as high risk who earlier would have chosen not to have invasive diagnostic testing, might now consider the DNA test as a safe way to obtain further information, before making a final decision."The US Centers for Disease Control and Prevention estimated in 1995 that about one in every 200 invasive diagnostic procedures will cause a pregnancy miscarriage.
Trisomy 18, also called Edwards syndrome, is a serious disorder with up to 70% of first trimester affected fetuses being spontaneously lost during pregnancies.Among those born alive, half die within a week with only 5% surviving the first year.All have serious medical and developmental problems.About 1,330 infants with trisomy 18 would be born in the US each year in the absence of prenatal diagnosis.Trisomy 13, also called Patau syndrome, is less common but equally serious.About 600 infants with trisomy 13 would be born in the US each year in the absence of prenatal diagnosis.Like Down syndrome, trisomy 18 and trisomy 13 are more common as maternal age increases.For comparison, about 7,730 Down syndrome cases would be born each year in the absence of prenatal diagnosis.Current prenatal screening tests for trisomy 18 and trisomy 13 rely on both biochemical and ultrasound markers.
This industry-sponsored project, awarded to Drs. Palomaki and Canick and Women & Infants Hospital in 2008, enrolled 4,500 women at 27 prenatal diagnostic centers throughout the world.Women & Infants also served as one of the enrollment centers under the direction of maternal-fetal medicine specialist and director of Perinatal Genetics, Barbara O'Brien, MD.
"It is clinically more relevant that all three trisomies can be detected by this test," said Dr. O'Brien."Having access to such a comprehensive, DNA-based test that can be done early in pregnancy will give us more information so that we can better guide which patients should consider diagnostic testing."

**Source: Women & Infants Hospital

Las comunidades dejaron de pagar a las farmacias 1.966 millones de euros en 2011



El año pasado acabó con una deuda de las comunidades autónomas a las oficinas de farmacia de 1.966 millones, según los datos del Observatorio del Medicamento de la Federación Empresarial de Farmacéuticos Españoles (FEFE). Fue toda una novedad para el sector, que hasta ahora se había librado de los impagos de las Administraciones (más de 10.000 millones solo a los laboratorios —6.000— y los proveedores de tecnología —los otros 4.000—, con pagos a casi dos años).
“El año pasado la deuda fue de menos del 20%, unos 400 millones, y se debía a ajustes por el fin de año que se cobraban enseguida”, ha dicho Enrique Granda, director del observatorio.
Para este año, las predicciones no son mejores. Este organismo de la patronal de los dueños de farmacia ha calculado que este año habrá nueve comunidades con problemas para pagarles. De tres —Cataluña, Murcia y Comunidad Valenciana— no tienen dudas porque ni siquiera han presupuestado una cantidad que cubra el gasto en medicamentos aun suponiendo que el importe de la partida baje 12% (el año pasado se redujo algo más de un 8% por los decretos de reducción de precios y la entrada en vigor de la prescripción por principio activo). Pero, siempre según los cálculos de Fefe, los farmacéuticos de Andalucía, Baleares, Canarias, Castilla-La Mancha, Madrid y Navarra también tendrán problemas para cobrar.
Estas son prácticamente las mismas comunidades que ya fueron morosas el año pasado, con la excepción de Navarra, que entraría en la lista, y La Rioja, que saldría.
Eso sí, que las comunidades no hayan pagado no implica que algunos de los farmacéuticos no hayan cobrado, indica Granda. Por ejemplo, en Madrid, la comunidad adeuda 202 millones, pero los dueños de las oficinas no lo han notado porque se ha cubierto con un crédito pedido por el colegio profesional. Son los que han tenido más suerte. En Murcia han tenido que pedir préstamos bancarios personales para mantener los negocios abiertos.
La solución de los créditos (personales o corporativos) no gusta a los profesionales, que quieren que, ante los recelos de las entidades financieras a descontar deuda de los Ejecutivos autónomos, sea el Gobierno central el que avale los créditos que deban pedir.
La deuda de las autonomías con las oficinas de farmacia ya representa el 17,7% del gasto. Aunque sea mucho, otros sectores, como los laboratorios, están mucho por, ya que les adeudan el 100%. La comunidad que más debía a 31 de diciembre de 2011 era la Valenciana (420 millones), seguida de Castilla-La Mancha (335) y Andalucía (300).
Para el año que viene quien peor ha presupuestado es Cataluña —salvo que el anunciado cobro de un euro por receta disminuya drásticamente la demanda—. Le siguen Murcia y la Comunidad Valenciana.



**Publicado en "EL PAIS"

Coffee consumption reduces fibrosis risk in those with fatty liver disease

Caffeine consumption has long been associated with decreased risk of liver disease and reduced fibrosis in patients with chronic liver disease. Now, newly published research confirms that coffee caffeine consumption reduces the risk of advanced fibrosis in those with nonalcoholic fatty liver disease (NAFLD). Findings published in the February issue of Hepatology, a journal of the American Association for the Study of Liver Diseases, show that increased coffee intake, specifically among patients with nonalcoholic steatohepatitis (NASH), decreases risk of hepatic fibrosis. The steady increase in rates of diabetes, obesity, and metabolic syndrome over the past 20 years has given rise to greater prevalence of NAFLD. In fact, experts now believe NAFLD is the leading cause of chronic liver disease in the U.S., surpassing both hepatitis B and C. The majority of patients will have isolated fatty liver which has a very low likelihood of developing progressive liver disease. However, a subset of patients will have NASH, which is characterized by inflammation of the liver, destruction of liver cells, and possibly scarring of the liver. Progression to cirrhosis (advanced scarring of the liver) may occur in about 10-11% of NASH patients over a 15 year period, although this is highly variable.
To enhance understanding of the correlation between coffee consumption and the prevalence and severity of NAFLD, a team led by Dr. Stephen Harrison, Lieutenant Colonel, U.S. Army at Brooke Army Medical Center in Fort Sam Houston, Texas surveyed participants from a previous NAFLD study as well as NASH patients treated at the center's hepatology clinic. The 306 participants were asked about caffeine coffee consumption and categorized into four groups: patients with no sign of fibrosis on ultrasound (control), steatosis, NASH stage 0-1, and NASH stage 2-4.
Researchers found that the average milligrams in total caffeine consumption per day in the control, steatosis, Nash 0-1, and Nash 2-4 groups was 307, 229, 351 and 252; average milligrams of coffee intake per day was 228, 160, 255, and 152, respectively. There was a significant difference in caffeine consumption between patients in the steatosis group compared to those with NASH stage 0-1. Coffee consumption was significantly greater for patients with NASH stage 0-1, with 58% of caffeine intake from regular coffee, than with NASH stage 2-4 patients at only 36% of caffeine consumption from regular coffee.
Multiple analyses showed a negative correlation between coffee consumption and risk of hepatic fibrosis. "Our study is the first to demonstrate a histopatholgic relationship between fatty liver disease and estimated coffee intake," concludes Dr. Harrison. "Patients with NASH may benefit from moderate coffee consumption that decreases risk of advanced fibrosis. Further prospective research should examine the amount of coffee intake on clinical outcomes."

**Source: Wiley-Blackwell

Scripps research scientists demonstrate effective new 'biopsy in a blood test' to detect cancer



Scientists from The Scripps Research Institute, Scripps Health, and collaborating cancer physicians have successfully demonstrated the effectiveness of an advanced blood test for detecting and analyzing circulating tumor cells (CTCs) -- breakaway cells from patients' solid tumors -- from cancer patients. The findings, reported in five new papers, show that the highly sensitive blood analysis provides information that may soon be comparable to that from some types of surgical biopsies. "It's a next-generation technology," said Scripps Research Associate Professor Peter Kuhn, PhD, senior investigator of the new studies and primary inventor of the high-definition blood test. "It significantly boosts our ability to monitor, predict, and understand cancer progression, including metastasis, which is the major cause of death for cancer patients."
The studies were published February 3, 2012, in the journal Physical Biology.
The new test, called HD-CTC, labels cells in a patient's blood sample in a way that distinguishes possible CTCs from ordinary red and white blood cells. It then uses a digital microscope and an image-processing algorithm to isolate the suspect cells with sizes and shapes ("morphologies") unlike those of healthy cells. Just as in a surgical biopsy, a pathologist can examine the images of the suspected CTCs to eliminate false positives and note their morphologies.
Kuhn emphasizes that this basic setup can be easily modified with different cell-labeling and image-processing techniques.




Five New Studies, Five Steps Forward
To test the new technology, members of the Kuhn lab at Scripps Research teamed up with pathologists and oncologists at Scripps Health in La Jolla, California; UC San Diego Moores Cancer Center at the University of California, San Diego; the Billings Clinic in Billings, Montana; the Division of Medical Oncology at the University of California, San Francisco; the Center for Applied Molecular Medicine at the University of Southern California, in Los Angeles; and the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital in Amsterdam, the Netherlands.
The five new studies that resulted from the collaboration not only demonstrate the accuracy and effectiveness of the new test for a number of different cancer types, but also begin to explore the utility of the technology for diagnosing and monitoring patients and improving cancer research in the lab. While other tests for CTCs typically use "enrichment" steps in which suspected CTCs are concentrated -- and these methods inadvertently exclude some types of CTCs -- the new studies show HD-CTC works well as a no-cell-left-behind process and enables a more complete analysis.
Also striking is the quality of the images. "The high definition method gives a detailed portrait of these elusive cells that are caught in the act of spreading around the body," said diagnostic pathologist Kelly Bethel, MD, of Scripps Health, Scripps Research, and UC San Diego School of Medicine, who is the senior clinical investigator on Kuhn's team. "It's unprecedented -- we've never been able to see them routinely and in high definition like this before."
In the first study, the research team examined 83 advanced cancer patients using HD-CTC to document the test's sensitivity and accuracy for different cancer types. The scientists found that the test detected five or more CTCs per milliliter of blood in 80 percent of patients with metastatic prostate cancer, 70 percent of those with metastatic breast cancer, 50 percent of those with metastatic pancreatic cancer, and no healthy subjects. The current gold-standard CTC test, known as CellSearch, was notably less sensitive in detecting tumor cells in these samples.
Most patients whose CTC counts surpassed the detection threshold also showed small aggregates of CTCs, which cancer biologists term "microtumor emboli." These are widely suspected to be incipient metastatic tumors, as well as triggers for the blood clots that often kill advanced cancer patients. In the second study, the scientists showed that HD-CTC could detect these aggregates in 43 percent of 71 patients with advanced prostate, lung, pancreas, and breast cancers, and in none of a group of 15 healthy subjects. "This tells us that HD-CTC could be helpful in studying the origins of cancer metastases and related blood clots, and for predicting them, too," Kuhn said.
In the third study, the team used HD-CTC to compare circulating tumor cells from prostate cancer patients with cells from prostate cancer cell lines that researchers often use as convenient models for prostate cancer biology in the lab. The team found significant differences between the two classes of cells, in their cell morphology and in the way they were labeled by HD-CTC's fluorescent tags. "This underscores the need for studying cancer cells from patients, not just model cancer cells that in some ways may be utterly different from the real thing," Kuhn said.
In the fourth study, the researchers performed HD-CTC tests on 28 patients with advanced non-small-cell lung cancer over periods of up to a year. The team was able to detect CTCs in 68 percent of samples, and found that the numbers of detected CTCs tended to go up as other measures showed cancer progression.
In the fifth and final paper of the series, the team used HD-CTC in 78 patients who had just been diagnosed with various stages of non-small-cell lung cancer. "We demonstrated that we could sensitively detect CTCs even in patients with early-stage cancer," Kuhn said.
This result points to the possibility of using the HD-CTC blood test not only to evaluate already-diagnosed cancer, but also to help detect cancer in people who are unaware they have it. "If HD-CTC works on the day after cancer diagnosis, as we've shown, then one can easily imagine that it would work the day before diagnosis, too," Kuhn said.
Kuhn and his colleagues now intend to study the use of HD-CTC as a potential screening test and to develop it further for use in clinical monitoring and cancer research. Kuhn has founded a San Diego-based biotechnology company, Epic Sciences, Inc., to develop HD-CTC commercially for companion diagnostic products in personalized cancer care.



EEUU: El NIC lanza 24 preguntas "olvidadas" sobre el cáncer



En una ocasión le preguntaron al médico y escritor Siddhartha Mukherjee, autor del celebrado libro 'El emperador de todos los males. Una biografía del cáncer', tres consejos para reducir el riesgo de desarrollar tumores. Respondió: "No fumar, no fumar, no fumar". Sin embargo, a pesar de las campañas y medidas que se promueven para evitarlo, un porcentaje significativo de la población fuma. ¿Cómo es posible?
El Instituto Nacional del Cáncer de EEUU (NCI, en sus siglas en inglés) considera prioritario resolver esta pregunta y otras 23 cuestiones "olvidadas" que requieren una respuesta urgente.
Harold Varmus, director del NCI y una figura clave de la investigación oncológica en las últimas cinco décadas, lidera una iniciativa que promueve una nueva generación de investigaciones en torno a "24 preguntas provocadoras".
Algunas cuestiones: ¿Por qué la obesidad se relaciona con un mayor incremento de cáncer? ¿Por qué cuesta tanto que se eviten factores relacionados directamente con un mayor riesgo de desarrollar tumores? ¿Se puede cuantificar la exposición a factores de riesgo? ¿Cómo identificar los biomarcadores que determinan el éxito de una terapia? El desarrollo de nuevas estrategias de prevención; la construcción de puentes entre la investigación básica y la práctica clínica; la mejora de los tratamientos, la definición de los tumores y los métodos de diagnóstico son los ejes del proyecto.
"Varmus, en su último papel, vuelve a sacudirlo todo", reza un artículo reciente publicado en 'Business Week'. El científico, de 72 años y premio Nobel en 1989 junto a su colega J. Michael Bishop por el descubrimiento de los oncogenes, vuelve a ser el gran agitador de la Oncología.
El proyecto del NCI tiene como objetivo "involucrar a una amplia variedad de científicos en un desafiante ejercicio intelectual", escriben en la última edición de 'Nature' Varmus y Ed Harlow (investigador de la Facultad de Medicina de Harvard y asesor del director del NCI).
La iniciativa se lanza con una financiación mínima para el primer año de 15 millones de dólares (alrededor de 11,3 millones de euros). El proyecto se inspira en otros similares que han establecido retos y plazos concretos para su consecución, como los Objetivos del Milenio de Naciones Unidas o empresas del mismo tipo impulsadas por la Fundación Gates y otras instituciones académicas.



-Talleres de trabajo
Para elaborar el cuestionario se organizaron talleres de trabajo con científicos, médicos e investigadores. Por ejemplo, un biolólogo evolucionista que participó en las discusiones propuso una de las preguntas, una de las muchas paradojas que con frecuencia surgen en la investigación: la rápida eliminación de las células tumorales con altas dosis de medicamentos se relaciona, en algunos casos, con la posterior aparición de resistencias a la terapia y, por tanto, con el fracaso del tratamiento.
Como el resto de cuestiones, se plantea el problema según un esquema fijo: la descripción y el planteamiento inicial, las posibilidades de encontrar una respuesta y, por último, el impacto que supondría el hallazgo de una solución. El cuestionario se estructura en seis grandes áreas: factores de riesgo, prevención, desarollo tumoral, detección, diagnóstico y tratamiento. La convocatoria para presentar trabajos de investigación está abierta.
"Durante los últimos 18 meses hemos desarollado la iniciativa de Preguntas Provocadoras desde el concepto a una estrategia pragmática para apoyar becas [de investigación]", afirman Varmus y Harlow. "Este abordaje ayuda a definir los límites entre lo conocido y lo desconocido".
El proyecto nace en un momento de recortes. Varmus, que fue director de los Institutos Nacionales de la Salud entre 1993 y 2000, tendrá en el NCI en 2012 un presupuesto de 5.070 millones de dólares (frente a los 5.100 millones de 2010). Pero el científico considera prioritario abordar las 24 preguntas del proyecto y volver a agitar la investigación oncológica.



**Publicado en "EL MUNDO"

Elevated glucose associated with undetected heart damage

A new study led by researchers at the Johns Hopkins Bloomberg School of Public Health suggests that hyperglycemia (high blood sugar) injures the heart, even in patients without a history of heart disease or diabetes. Researchers found that elevated levels of glycated hemoglobin (HbA1c), a marker for chronic hyperglycemia and diabetes, were associated with minute levels of the protein troponin T (cTnT), a blood marker for heart damage. The high-sensitivity test they used detected levels of cTnT tenfold lower than those found in patients diagnosed with a heart attack. The findings, which are published in the latest issue of the Journal of the American College of Cardiology, suggest that hyperglycemia may be related to cardiac damage independent of atherosclerosis.
"Hyperglycemia and diabetes are known to be associated with an increased risk for heart attack and coronary disease and our study sheds some light on what may be happening," said Elizabeth Selvin, PhD, MPH, senior author of the study and associate professor in the Bloomberg School's Department of Epidemiology. "Our results suggest that chronically elevated glucose levels may contribute to heart damage."
For the study, the researchers followed 9,662 participants from the Atherosclerosis Risk in Communities (ARIC) study. None of the participants had coronary heart disease or history of heart failure. Higher levels of HbA1c were associated in a graded fashion with elevated levels of high-sensitivity cTnT. This relationship was present at HbA1c levels even below the threshold used to diagnose diabetes. Using conventional tests, troponin T can be detected in 0.7 percent of the population and is associated with heart attacks and death. With the high-sensitivity cTnT test, low levels of troponin were found in 66 percent of the study population.
"Our study hints at other potential pathways by which diabetes and elevated glucose are associated with heart disease. Mainly, glucose might not only be related to increased atherosclerosis, but potentially elevated glucose levels may directly damage cardiac muscle," said Jonathan Rubin, MD, general internal medicine fellow at the Johns Hopkins School of Medicine. He was lead author of the study while studying at the Johns Hopkins Bloomberg School of Public Health.

**Source: Johns Hopkins University Bloomberg School of Public Health

Utilizar tacones altos reduce la capacidad de rotación del tobillo

Los hay de aguja, más gruesos, más altos y más bajos... Usted puede elegir los tacones que más le gusten, pero si va a ser para uso habitual, tenga en cuenta algunas recomendaciones. Según un estudio que acaba de publicar la revista 'American Physiological Society', si los suyos son de unos cinco centímetros y los utiliza un mínimo de 40 horas a la semana, en el transcurso de dos años empezarán a aparecer lesiones en sus pies.
Como explican los autores de la investigación, de la Universidad Jyväskylä (Finlandia), se sabía que el uso frecuente y prolongado de tacones altos acorta los músculos de los gemelos y aumenta la rigidez del tendón de Aquiles. Sin embargo, "apenas se han estudiado las consecuencias de estos cambios". Ahora, este estudio demuestra que sólo hacen falta dos años para que los pies presenten signos de sufrimiento. "Aumenta la tensión gemelar y la fatiga de los músculos de esta zona, lo que repercute en la eficacia a la hora de caminar, es más incómodo e incluso genera dolores".
Así lo observaron los investigadores después de analizar el comportamiento de los músculos durante el paseo (lo que se conoce como la neuromecánica, es decir, parámetros cinemáticos, cinéticos y neurales) del paseo en 19 mujeres. Nueve llevaba tacones de un mínimo de cinco centímetros durante unas 40 horas a la semana y 10 apenas los usaban 10 horas. La participantes caminaron sobre una plataforma instalada en el laboratorio y se evaluaron aspectos como la fuerza de reacción del tobillo, la dislocación de la rodilla, la resistencia de los tríceps, la longitud de los músculos del gemelo, etc.
Lo primero que vieron fue que la tensión muscular era mucho mayor con el uso habitual de los tacones y, además, "la capacidad de rotación del tobillo era significativamente menor". Como explican los expertos, "se pierde flexibilidad, aumenta la tensión de los músculos de la zona y también el riesgo de lesiones".

-Cambios en la forma de caminar
Este hábito empieza por cambiar la biomecánica de la marcha, es decir, se camina de forma distinta (la posición de la espalda tira un poco hacia adelante) y, después, con el tiempo, se producen modificaciones estructurales, sobre todo a nivel del tobillo, aunque también repercute en las rodillas, la cadera y la columna vertebral.
Como argumenta Christian Cora, podólogo del Instituto de Biomecánica de Valencia, "este tipo de calzado eleva el talón y transmite todo el peso sobre la parte delantera del pie (los huesos metatarsianos)". Esta es precisamente la "principal causa por la que la mayoría de las mujeres que usan tacones altos presentan callosidades en dicha zona". Además, se observan "modificaciones en los tejidos blandos, los huesos soportan más peso y, por tanto, se forma engrosamiento e inflamaciones; también promueven o aceleran la progresión de los popularmente conocidos como juanetes".
Según el último estudio realizado en el Instituto de Biomecánica de Valencia, "el 100% de las usuarias presentaba callosidades, más del 50% sentía también dolor, entre el 25% y el 30% notaba inestabilidad del tobillo y el 5% había tenido algún esguince", señala Christian Cora. En dicho trabajo, "vimos que el estrés al que se somete la parte delantera del pie hace que los dedos empiecen a deformarse".
Según Juan Carlos González, director de Indumentaria del Instituto de Biomecánica de Valencia, especializado en el estudio del diseño del calzado para el confort y la mejora de problemas a largo plazo, "lo ideal para un zapato de uso diario es que el tacón no supere los 2-3 centímetros, que tenga una plantilla blandita y una horma adecuada que no apriete y sea cómoda".

**Publicado en "EL MUNDO"

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