Day: 12/12/2011

Is Older Blood Safe for Transfusion?

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Use of blood stored for 40 to 42 days increased levels of bilirubin, ferritin, and nontransferrin-bound iron and enhanced growth of pathogenic Escherichia coli bacteria.

Current guidelines permit storage of blood for as long as 42 days after collection. However, during storage, red cells lose 2,3 bisphosphoglycerate and undergo other changes that shorten their life span. Moreover, phagocytosis of these stored, transfused cells is associated with iron release, with potentially adverse consequences.

Now, investigators have examined the safety of giving stored blood to 14 healthy adult volunteers. Each volunteer donated a leukoreduced, double red blood cell unit and was subsequently transfused with one “fresh” unit after it was stored for 3 to 7 days and with one “older” unit after it was stored for 40 to 42 days. Results of blood samples taken after each transfusion were as follows:

  • Incremental hemoglobin increase, serum haptoglobin, lactate dehydrogenase, and basic metabolic parameters (including potassium) were similar after transfusion of fresh or older blood.
  • Bilirubin levels were increased after transfusion of older versus fresh blood; the peak mean increase of unconjugated bilirubin was 0.55 mg/dL 4 hours after transfusion (P=0.0002).
  • 4 hours after transfusion, those who received older versus fresh blood experienced increased serum iron and transferrin saturation (P=0.001 and P=0.0005, respectively); the peak values for both parameters were above the reference range in 13 of the 14 volunteers.
  • Ferritin increased from baseline levels only after transfusion of older blood and peaked at 15.5 ng/mL 24 hours after transfusion.
  • Circulating nontransferrin-bound iron (NTBI) increased only after transfusion of older blood, rising progressively between 1 and 4 hours after transfusion to a peak mean of 3.2 μM over baseline (P=0.002).
  • Serum samples collected 2 to 4 hours after transfusion showed that older blood, but not fresh blood, supported enhanced growth of pathogenic Escherichia coli; the growth curves correlated with the mean changes in NTBI (r=0.94; P=0.002).

Comment: Extending storage times has improved blood availability but has also raised concerns that the quality of the product has suffered. Older, stored red blood cells are more likely to undergo rapid phagocytosis after transfusion, increasing levels of bilirubin and NTBI. The unbound iron supports bacterial growth and might explain the increased infection rate and perhaps other adverse effects associated with transfusion of older units of blood.

source: Journal Watch Oncology and Hematology

Consensus Criteria Predict Futile Prehospital Trauma Resuscitation

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None of 294 patients had meaningful survival, and EMS resuscitation triggered hospital costs approaching $4 million.

In 2003, the National Association of Emergency Medical Services (EMS) Physicians and the American College of Surgeons Committee on Trauma published guidelines on when to withhold or terminate prehospital resuscitation in traumatic cardiopulmonary arrest (TCPA). Using data from a level I trauma registry from 2003 through 2010, researchers studied prehospital TCPA patients aged ≥18 years for whom these guidelines were violated. Criteria to withhold or terminate care were (1) blunt trauma with apnea, pulselessness, and no organized electrocardiogram activity; (2) penetrating trauma with the preceding clinical presentation and no other signs of life; (3) ≥15 minutes of cardiopulmonary resuscitation without return of spontaneous circulation; or (4) EMS-witnessed TCPA followed by ≥15 minutes of unsuccessful resuscitation en route to the emergency department (ED).

Among 294 patients, mechanism of injury was blunt in 90 (31%) and penetrating in 204 (69%). Overall, 274 patients (93%) died in the ED, and 12 (4%) died during surgery. Of the 8 patients who reached the intensive care unit, 7 died in the ICU, and 1 (0.3%) survived but had a Glasgow Coma Scale score of 6 and was discharged to a long-term care facility.

Comment: The charges for hospital care for these 294 patients totaled nearly US$4 million, and the one surviving patient had a horrible outcome. These data strongly support the existing guidelines and the need to ensure that EMS personnel understand and adhere to them.

source:Journal Watch Emergency Medicine

U.S. Genome Centers Expand to Rare Diseases, Clinical Genomics

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The U.S. government is renewing its push to move genomics towards the clinic. Today the National Human Genome Research Institute (NHGRI) announced its latest 4-year genome sequencing program, funded at $416 million over 4 years. NHGRI’s “flagship” sequencing program will expand beyond three huge centers and “sharpen its focus on medical applications,” said NHGRI Director Eric Green in a press call today.

The big three are still on top: 77% of the money, or about $319 million, will go to these existing centers. They include the genome center at the Broad Institute in Cambridge, Massachusetts, headed by Eric Lander, which will receive $35.9 million the first year; a center at Washington University in St. Louis, led by Richard Wilson, which received an initial $28.4 million; and Baylor College of Medicine in Houston’s center directed by Richard Gibbs, which won $21.3 million. These centers were workhorses in completing the Human Genome Project, and now they will continue to sequence thousands of people’s genomes. The centers are also cataloging genetic changes in human tumors together with the National Cancer Institute.

Despite ever-cheaper and faster sequencing technologies that now allow even a small lab to sequence an entire human genome, there is still a need for the big centers to explore genome biology, test out new technologies, and find better ways to analyze the data, say NHGRI officials. “We believe that large scale approaches continue to provide exciting opportunities,” said NHGRI Deputy Director Mark Guyer. However, because sequencing costs continue to decline, the centers’ grants will drop 5% a year.

For the first time, the sequencing program will also fund some smaller centers. Three will hunt for mutations underlying rare inherited diseases caused by a glitch in a single gene. Labs that will share $40 million over 4 years from NHGRI (and another $8 million from the National Heart, Lung, and Blood Institute), include: a $5.2 million a year center at the University of Washington, headed by Deborah Nickerson and others; a $2.8 million a year center at Yale University, led by Richard Lifton and others; and a joint center with $4 million per year led by David Valle at the Johns Hopkins University and Baylor’s James Lupski.

These centers will follow on recent successes with sequencing part or all of genomes to track down genes behind the more than 6000 so-called Mendelian disorders; less than half are known so far. The results will improve diagnosis and possibly lead to new treatments. The centers already have DNA from patients with hundreds of diseases and will study “as many disorders as possible,” depending on technologies and how many more samples they can gather, said NHGRI Mendelian centers program director Lu Wang.

Another $40 million will go for five multidisciplinary teams—including scientists, physicians, ethicists, and patients—to explore using genome sequencing as part of routine medical care. They will examine questions such as how to add genomics to health records, and when to tell patients about unexpected genomic findings not related to the disease they’re being treated for. And around $20 million not yet awarded will fund software to handle the genome data deluge.

 

source: scienceNow

Do Presidents Age Faster Than the Rest of Us?

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Three years into his presidency, Barack Obama has far more wrinkles and grayer hair than when he was a senator from Illinois. And Bill Clinton left the White House looking more than 8 years older. It seems like presidents age faster than people with normal jobs—one physician has suggested that they age twice as fast. But a new study, published today in the Journal of the American Medical Association, finds that it’s not all bad for American leaders. By comparing presidents to other men of their eras, researchers discovered that commanders in chief die at about the same age as their peers. They certainly don’t age at double the speed. Many live longer, probably because most have been wealthy, college-educated, and able to get good medical care. So why does being in office wrinkle presidents? Probably, the researchers say, because they’re just getting older like the rest of us.

source: ScienceNOW

First ‘Mini-Earth’ May Have Been Spotted

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NASA’s Kepler space telescope appears to have confirmed the existence of an alien world smaller than our own Earth—the first time such a planet has been discovered around a star like our sun. However, scientists are reluctant to provide any details about the find—announced on Tuesday at the First Kepler Science Conference here at NASA’s Ames Research Center—before their work is published, probably early next year.

Despite its size, the new world—provisionally dubbed KOI-70.04—is very unlike our home planet. It orbits its star, a sun similar to our own known as Kepler-20, at a distance of just 9.6 million kilometers, completing one circuit every 6.1 days. Surface temperatures probably soar to almost 600°C, so there’s no hope of finding liquid water there, let alone life.

Just like Earth, KOI-70.04 is part of a multiplanet system. Four other, larger planets orbit the same star—one even closer in, and three farther away. All five planets are closer to their star than Mercury is to the sun. In that respect, the planetary system resembles Kepler-11, an extremely compact system of six planets announced in February.

The Kepler telescope, launched in March 2009, scrutinizes over 150,000 stars for tiny periodic dips in brightness that might mean orbiting planets are passing in front of the stars, blocking part of their light from reaching the telescope. But other observations need to confirm the true planetary nature of these candidate events, because the observed dips may also be due to an eclipsing binary star in the background whose light blends with the foreground star studied by Kepler. An eclipse within the background binary would mimic a small brightness dip in Kepler-20.

The best way to confirm a candidate planet is by measuring the small, periodic wobbles it induces in its parent star. If that doesn’t work, astronomers have a couple of other tricks up their sleeves to validate the planet.

Kepler project scientist Nick Gautier of NASA’s Jet Propulsion Laboratory presented new data at the meeting on three of the larger planets in the Kepler-20 system, now officially known as Kepler-20b, -20c and -20d. From the star’s wobbles, observed with ground-based telescopes, Gautier and his colleagues were able to deduce the masses of Kepler-20b and -20c: 8.7 and 16.1 Earth masses, respectively. Kepler-20d, the outermost planet in the system, was found to weigh in at less than 20.1 Earth masses. The three planets are between 1.9 and 3 times the size of Earth.

So what about the other two? “I can’t disclose any details yet,” says François Fressin of the Harvard Smithsonian Center for Astrophysics in Cambridge, Massachusetts, who has a paper about the two smaller planets in press with Nature, “but if they are also validated, and if their size estimates are right, KOI-70.04 is significantly smaller than the Earth.” KOI-70.04 was already in Kepler’s list of candidate planets back in February, together with the three Kepler-20 planets described by Gautier; KOI-70.05 was found in June.

Fressin won’t confirm whether the two planets have indeed been validated, but if they weren’t, they probably wouldn’t warrant a Nature publication. Moreover, according to theoretical astrophysicist Jack Lissauer of NASA’s Ames Research Center, “most Kepler multicandidates must be real planets.” The reason is simple statistics: It’s extremely unlikely to encounter two background eclipsing binaries (or one background binary and one genuine planet) at the same location.

Indeed, asked about Kepler-20, Daniel Fabrycky of the University of California, Santa Cruz, confirmed that it is the first genuine five-planet system found by the space telescope. But while Fressin agrees that Lissauer’s statistical argument is strong, he says validation of a candidate planet, especially one as small as KOI-70.04 appears to be, is of paramount importance. “I can’t tell you anything more at this moment,” he says.

From the data published in February and the new estimates for the properties of the parent star presented by Gautier, it would follow that KOI-70.04 is between 80% and 90% of the size of Earth. For KOI-70.05, no data have been released yet, except its orbital period, which, according to Gautier, is 19.6 days. In Fressin’s upcoming Nature paper, the two planets will almost certainly be renamed Kepler-20e and Kepler-20f.

Earlier this week, Kepler scientists announced the discovery of Kepler-22b, a relatively large planet (2.4 Earth diameters) in the habitable zone of its parent star, where temperatures allow the existence of liquid water. With Kepler-20e, they have bagged a real Earth-sized planet, albeit much too close to its star to harbor life. It probably won’t be too long before the planet hunters hit upon their Holy Grail: a planet just like Earth in the habitable zone of a sunlike star. Stay tuned.

Source:ScineceNow

The Brain of a Cabbie

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London taxi drivers aren’t like the rest of us. Researchers have known for more than a decade that these elite cabbies—who train for years to master “the Knowledge,” a mental map of 25,000 streets—have a larger than average rear hippocampus, a brain region linked to learning and navigation. What scientists didn’t know was whether the drivers grew bigger hippocampi as they trained or whether they had big ones (and thus an innate navigation advantage) to begin with. So a team followed three groups—trainees who successfully acquired the Knowledge and became cabbies, trainees who failed to qualify, and a control group of non-taxi drivers—over 4 years, testing them and scanning their brains before, during, and after training. They found that the brains of qualifying trainees were no different from those of nonqualifying trainees or non-taxi drivers before beginning training. But as the cabbies learned the Knowledge, their hippocampi grew, literally changing their minds, the researchers report online today in Current Biology. The hippocampi of unsuccessful trainees stayed the same throughout, which could suggest that successful cabbies really do have an innate advantage—their brains are more malleable than others’.

source: scienceNOW

Sniffing Out the One in a Quadrillion

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Detecting tiny amounts of gases might seem dull, but when it comes to spotting traces of toxic substances that are intended for chemical attacks, it can make the difference between life and death. Now, scientists have improved the sensitivity of gas detection almost 1000 times over, paving the way for more-rigorous security operations and even a novel way of performing carbon dating. The method requires a gas mixture—perhaps sampled from a suspect area—to be injected via a tube into a cavity with parallel mirrors on each side. When laser light is shone into the gas mixture, it bounces back and forth between the mirrors so many times that it clocks up about 10 kilometers. Over this distance some of the light is absorbed, and the wavelength at which it is absorbed reveals what types of molecules are present. Tested on a carbon dioxide mixture, the method detected a minuscule component—just 43 parts in every quadrillion—that contained radioactive carbon atoms rather than normal carbon atoms, the team will report later this month in Physical Review Letters. Aside from more sensitive detection of chemical-warfare agents, the technique offers a cheaper and simpler way to age artifacts via carbon dating, which usually requires huge particle accelerators to extract radiocarbon atoms from a sample.

source:Science Now

Steps Women Can Take to Reduce Risk of Breast Cancer

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Some Steps Are Proven, Others May Be Recommended but Still Need Research

Women can reduce their risk of breast cancer by not taking combination estrogen/progestin hormone therapy, not smoking, minimizing their exposure to radiation during CT scans and the like, avoiding weight gain after menopause, cutting back on alcohol, and staying active, a new report says.

“The potential risk reductions from any of these actions for any individual woman will vary and may be modest,” according to a brief summary of the nearly 400-page Institute of Medicine report, presented at the San Antonio Breast Cancer Symposium. “Because much of the evidence on breast cancer risk factors has come from studies of postmenopausal breast cancer in white women, it is hard to judge the potential benefit for younger women or women of other races.”

The report, requested by Susan G. Komen for the Cure, examines what’s known about the link between breast cancer and any factors other than those directly inherited through genes, which it refers to as “environmental factors.”

“Such factors include how a woman grows and develops during her lifetime; what she eats and drinks; the physical, chemical, and microbial agents she encounters; how much physical activity she engages in; medical treatments and interventions she undergoes; and social and cultural practices that she experiences,” according to the summary brief.

The Institute of Medicine (IOM), part of the National Academies, provides independent advice to policy makers, the private sector, and the public.

Much Left to Learn

More than 230,000 U.S. women are expected to be diagnosed with breast cancer this year. Despite decades of research costing millions of dollars, much about how environmental factors contribute to breast cancer risk remains unknown, Irva Hertz-Picciotto, PhD, chair of the IOM’s Committee on Breast Cancer and the Environment, said at a news conference.

“The evidence is less than persuasive but suggests a possible association with increased risk” for such factors as secondhand smoke, nighttime shift work, and exposure to such chemicals as benzene and ethylene oxide, chemicals found in some vehicle and workplace fumes and tobacco smoke, according to the committee.

Animal studies have shown that that some environmental agents, such as the chemical bisphenol A (BPA) — widely used in plastic containers — are at least biologically plausible risk factors, but studies in humans are lacking, the panelists say.

Ideal Study Hard to Do

Part of the problem is that environmental exposures begin in the womb and continue throughout life, so tracking them is virtually impossible, committee member Robert Hiatt says.

The ideal study would follow individuals for that entire span, he says, but that would be prohibitively expensive and time-consuming.

“The breast undergoes substantial changes over a woman’s lifetime,” the committee members note. “Future research should emphasize a ‘life course’ model.”

Testing of chemicals in animals often occurs too late in their life span to provide clues about the impact of early exposures in humans, says panel member David Eaton, PhD, professor of environmental and occupational health sciences at the University of Washington.

“Also,” says Hertz-Picciotto, professor of public health sciences at the UC Davis Health System, “we need to consider possible combined effects of many low-level exposures.”

Still, Hiatt says, “I actually think the time is very exciting for getting some place in this area.”

For example, he says, some studies are now looking at what determines the age at which girls enter puberty. Previous research has shown that the earlier the onset of puberty, the greater the breast cancer risk in adulthood.

And sophisticated molecular approaches can now uncover “fingerprints” left behind by exposures long ago, says Cheryl Lyn Walker, PhD, director of the Institute of Biosciences and Technology at the Texas A&M Health Science Center.

Source:webMD

FDA advisers: Ortho Evra patch needs clearer label

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U.S. drug advisers recommended that the label for Johnson and Johnson’s Ortho Evra birth control patch be simplified to better explain the risk of blood clots.

In a 20 to 3 vote with one abstention, advisers to the Food and Drug Administration found that the current label for Ortho Evra inadequately reflects the risks women face by using it. It is the only contraceptive patch sold in the United States.

The panel voted 19 to 5 that the patch’s risks were outweighed by its benefits, such as pregnancy prevention through a once-weekly application.

“I’m satisfied generally with what the content is for this label, it’s the understandability and presentation that needs some work,” said Jacqueline Gardner, panel member and a University of Washington professor.

All commonly used birth control pills increase women’s chances of getting blood clots. The patch, approved in 2001, has been linked to an even higher risk as it contains a much greater amount of the hormone estrogen than a pill.

The current label, which has undergone numerous revisions over the past decade, has a boxed warning of a higher risk compared to older birth control pills. But a new FDA study earlier this year again showed that women using the patch were about 60 percent more likely to experience venous thrombotic events (VTEs).

With VTEs, blood clots occur in one of the deep veins in the body, such as the leg or pelvis, and then may travel to the lungs, which could lead to stroke or death.

The same group of advisers on Thursday recommended a more detailed description of blood clot risks and studies for a popular new generation of contraceptive pills, such as Bayer AG’s Yaz and Yasmin.

Those pills contain the compound drospirenone, which has been linked to higher risk of venous and arterial thrombotic events, when a blood clot forms in a leg and can travel to the lung to cause stroke or even death. Ortho Evra does not contain that compound.

“Yesterday we were looking at just another pill, there was no additional benefit to offset additional risk,” said Michele Orza, policy analyst at the National Health Policy Forum who represented consumers at the panel.

“In this case, I think there is additional risk but it is a unique kind of product. There is no alternative (patch) for women who desire hormonal contraception but can’t take the pill for some reason.”

Of all contraceptive alternatives to pills and intra-uterine devices in the United States, the Ortho Evra patch is the second most popular behind Nuvaring, Merck & Co Inc’s vaginal ring, according to IMS Health data. Sales of the patch reached $124 million last year, according to IMS, which is a nearly 50 percent decline over the past five years.

Source: FDA

 

Vitamin D and diabetes

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On the basis of evidence from animal and human studies, vitamin D has emerged as a potential risk modifier for type 1 and type 2 diabetes (type 1 diabetes and type 2 diabetes). Vitamin D is thought to have both direct (through activation of the vitamin D receptor) and indirect (via regulation of calcium homeostasis) effects on various mechanisms related to the pathophysiology of both types of diabetes, including pancreatic beta-cell dysfunction, impaired insulin action and systemic inflammation. Observational case-control studies have shown that vitamin D supplementation in pregnancy or early childhood is associated with reduced risk of incident type 1 diabetes. There are no trials on the effect of vitamin D (ergocalciferol or cholecalciferol) on type 1 diabetes. An association between vitamin D insufficiency and incident type 2 diabetes has been reported in longitudinal observational studies, but the association is not consistent. Results from small underpowered trials and post-hoc analyses of data from larger trials designed for bone-specific outcomes show no effect of vitamin D supplementation on glycemia in healthy adults but vitamin D may retard the progression to diabetes in adults with glucose intolerance. Because vitamin D is an excellent marker of general health status, the positive results reported in some observational studies might reflect unmeasured and unaccounted confounding. Therefore, the hypothesis that vitamin D may modify diabetes risk needs to be confirmed in trials specifically designed for that purpose.

Source:Science Direct