Doctors at the in Ohio have found that patients who receive blood that is more than 14 days old are nearly two-thirds more likely to die than those who get newer blood.

The survey of more than 9000 heart surgery patients also suggests that recipients of older blood are more at risk from blood poisoning and organ failure.

The conclusion? “Blood should be classified as outdated earlier than current recommendations,” says lead researcher Colleen Koch.

Koch’s team note that in the US the average age of transfused blood is more than two weeks – and that around half of all heart surgery patients receive blood transfusions.

New measures are urgently needed, say the researchers, to prevent unnecessary deaths among this large and vulnerable group of patients.

Previous studies have suggested that transfusions increase the risk of death and serious complications. This latest study suggests the age of the blood used is a major factor.

Broken blood

On the basis of earlier laboratory studies, Koch speculates that, at the two-week stage, stored red blood cells begin to break down. This, she says, may make them more likely to block blood vessels while reducing their capacity to carry oxygen.

Her team studied the medical records of patients who received major heart surgery at the Cleveland Clinic between June 1998 and January 2006.

A total of 2,872 patients received blood that had been stored for 14 days or less, and 3,130 patients received blood that was more than 14 days old.

The mean storage age was 11 days for the newer blood and 20 days for the older blood.

In-hospital mortality was significantly higher among those who received older blood: 2.8% compared to 1.7%.

The researchers also found that death rates a year on were nearly half as high again in the patients who had received older blood, compared to those who received newer blood. 11% of the patients who had received older blood had died a year later, compared to 7.4% of those who received newer blood. Both sets of patients received the same volume of blood.

“This research suggests that the longer transfused blood has been stored, the greater the risk of complications following cardiac surgery,” says Peter Weissberg of the UK charity, the . He says that research last year indicated that, in many heart surgery patients, .

“Together, these studies suggest that only those heart patients whose lives are at serious risk without a transfusion should receive blood,” Weissberg says.

“Further research is urgently needed to clarify the indications for transfusion and the effects of blood storage on outcome.”

There are around 30,000 heart operations every year in the UK, and over 100,000 in the US.

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, the genetic disease in question, results in the formation of smaller red blood cells, which contain less of the oxygen-carrying, iron-containing pigment, haemoglobin.

But the plus side of this form of iron deficiency, common in the tropics, is that it seems to mitigate the effects of malaria infection.

In the mid-1990s, researchers working on the north coast of Papua New Guinea showed that children there with mild alpha thalassaemia – around two thirds of the total child population – were 60% less likely to get severe malarial anaemia than unaffected children. This confirmed observations first made 50 years ago.

Just how the anaemic children were protected against the malarial anaemia, however, was unknown.

Some researchers speculated that the abnormally small red blood cells of thalassaemia sufferers were more resistant to attack by the malaria parasite.

Numbers game

Now , a tropical medicine specialist at New York University School of Medicine, has dispelled that theory – and provided a convincing alternative.

Day and colleagues reanalysed the Papua New Guinea data. They looked at red blood cell counts in each of 800 children with malaria, and compared this with the children’s genetic profiles.

Thalassaemic children have more red blood cells than unaffected children. But after the drastic loss of cells following a malaria attack, children with alpha thalassaemia end up with more total haemoglobin than those without. Compared with unaffected children, thalassaemic children could also cope with losing 10% more red blood cells to parasites before becoming severely anaemic.

There was no difference between the number of parasites in the blood of thalassaemia sufferers and unaffected children. This finding rules out the idea that the smaller cells of thalassaemic children are harder to infect.

Instead, say the researchers, the results suggest that thalassaemia protects against malaria through a “safety in numbers” strategy that allows more cells to survive an attack by the parasite. Since thalassaemic children have more red blood cells, more are likely to escape infection by the parasite.

Sticky sickle

“It is really remarkable and so simple. Children with alpha thalassaemia have adapted to the loss of red blood cells associated with malarial disease by making more of these cells, with less haemoglobin,” says Day.

“This does look like a novel and plausible explanation for how alpha thalassaemia protects against malaria,” says , a malaria expert at Imperial College London.

He notes that the study follows shedding new light on how another inherited red blood cell disorder, sickle cell disease, protects against malaria.

That paper suggested the abnormal, sickle-shaped cells of sufferers were less “sticky” and therefore less likely to clog the blood vessels of the brain following infection by the malaria parasite.

Journal reference: , DOI: 10.1371/journal.pmed.0050056

The condition – constant, painful erections in the absence of arousal – is embarrassing and potentially dangerous. In the worst cases it can lead to permanent erectile dysfunction or even gangrene.

Now relief is at hand – researchers at the University of Texas Medical School at Houston say they have figured out the biochemical basis of the disorder.

Raised levels of the biochemical adenosine – which can cause blood vessels to dilate and has the potential to influence blood flow into the penis – seem to be the cause, says team leader .

To test the idea, the team used mice genetically altered to be deficient in an enzyme that breaks down adenosine. As a result the animals have very high adenosine levels.

Safe treatment

Sure enough, these animals experienced constant erections. When they were given a chemical called polyethylene glycol–ADA that reduces but does not eliminate adenosine, the problem quickly subsided.

“There are tremendous clinical implications,” says Xia. “We hope this might lead to adenosine-blocking treatment that will prove very effective.”

Xia says that further studies are needed to see if raised adenosine levels also lie behind the much rarer female priapism, in which the clitoris becomes swollen.

She notes that polyethylene glycol-ADA, which proved so effective in treating the genetically altered male mice, has already been licensed to treat children with a similar, rare enzyme deficiency.

“So safety should not be an issue,” she says. She hopes that trials on male priapism sufferers will begin this year. Current treatments are invasive, requiring the draining of blood from the erectile tissue of the penis.Sickle cell link

‘Embarrassing condition’

New treatments would be particularly welcome in men with blood disorders such thalassaemia and sickle cell disease, some 40% of whom show symptoms of priapism.

Xia’s theory appears to have been backed by follow-up tests on mice with sickle cell disease. The tests have already indicated that these animals are less likely to suffer priapism when levels of adenosine are controlled.

Craig Robson, a biochemist at Newcastle University, UK, who specialises in urological problems, says the research is a real advance.

“This exciting finding opens up the possibility of therapeutic intervention for this potentially embarrassing medical condition by blocking the receptor for adenosine,” he says.

The condition is named after the Greek god Priapus who according to myth received a huge but useless set of wooden genitals from the other gods as punishment for sexual transgressions.

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Human embryonic stem cells produce a protein which shows some anti-cancer properties in the lab, according to a new study.

The potential for stem-cell therapies to cause cancer is a major concern, but now researchers at in Chicago, US, say a protein produced by human embryonic stem cells (hESCs) can inhibit the growth and spread of breast cancer and malignant melanoma, the deadliest form of skin cancer.

They suspect that the protein, called Lefty, has similar effects on other tumour types, including those of the prostate.

The similarities between stem cells – primitive cells which can differentiate into the body’s different tissue types – and tumour cells have intrigued researchers. Both are self-renewing and have the capacity to give rise to different cells types.

The team at Northwestern previously showed that hESCs – the most versatile type of stem cell – produce chemicals that caused melanoma cells to revert to normal skin cells.

They also demonstrated that melanoma and breast cancers produce a protein that helps tumour cells spread, and that this protein also facilitates embryonic stem cell’s ability to turn into different cell types.

Tumours controlled

In the latest study they set out to find the substances produced by hESCs that have anti-cancer properties – perhaps, they believed, by blocking Nodal.

Lefty, the protein they identified, blocks the production of Nodal and therefore controls embryonic cell differentiation and development.

Mary Hendrix, who led the study, showed that unlike hESCs, however, tumour cells do not express Lefty. This allows them to produce Nodal in an unregulated manner – and to keep growing and spreading.

But when the researchers exposed aggressive tumour cells to the chemical environment of hESCs, which contained Lefty, levels of Nodal production fell sharply, and the tumour cells became less invasive and even started to die.

Hendrix told ��è����Ƶ she was optimistic that anti-cancer treatments based on stem cell proteins such as Lefty would emerge. “We now hope to interest pharmaceutical or biotech companies into developing partnerships to develop new treatments. We really believe that we are onto something important.”

She adds that other stem cells proteins with anti-cancer effects probably remained to be discovered.

Embryonic source

Significantly, Hendrix notes that Lefty is secreted only by hESCs, and not by any other stem-cell type tested – including stem cells isolated from amniotic fluid, cord blood or adult bone marrow – or placental cells.

“After all the controversy about using embryonic stem cells, this shows how potentially important such research is,” she says.

at Newcastle University in the UK says the latest study is “convincing” in showing the prominent role the Nodal protein plays in aggressive cancers. He says more research is needed to see if other types of cancer respond equally well when the pathway is switched off.

“The paper clearly shows that factors which probably promote human embryonic stem cell proliferation are important in controlling tumour cell behaviour,” notes , director of the stem cell biology laboratory at Kings College London. “This provides a novel target for developing tumour cell therapies.”

Journal reference: (DOI: 10.1073__pnas.0800467105)

Cancer – Learn more about one of the world’s biggest killers in our comprehensive special report.

Stem Cells – Learn more about the promise and the controversy in our cutting edge special report .

The number of tongue, mouth and throat cancers due to the sexually transmitted human papilloma virus (HPV), which can also cause cervical cancer in women, rose by about a third from 1973 to 2004, say researchers.

The team led by Maura Gillison at Johns Hopkins University in Baltimore, Maryland, US, studied trends in oral cancers recorded by US National Cancer Institute registries.

Earlier work by this team and others had established a link between certain strains of the common sexually transmitted virus and oral cancer. The latest study, which looked at nearly 46,000 cases, is the first to quantify an increase in mouth and throat cancers due to sexual activity.

‘Vaccinate boys’

“What we do know is that the prevalence of HPV is high, particularly among young people and this shouldn’t be a surprise given that, since the sexual revolution, people have been having more sexual partners,” says Lesley Walker, director of cancer information at .

The rise was largest among young white males, suggesting this group is more likely to have oral sex at a younger age now than it was 20 years ago, says Gillison’s team. It adds that further research on the role of race and sex, and oral sexual behaviour, is needed.

What is not in doubt, says Gillison, is the need to consider giving boys the HPV vaccine, to protect them from the disease.

A Merck vaccine is currently licensed for use in young women and girls to protect them against the most common cervical cancer-causing strains of HPV. These strains are also thought to cause oral cancer, as well as penile and anal cancer.

“We need to start having a discussion about those cancers other than cervical cancer that may be affected in a positive way by the vaccine,” urges Gillison.

Cost concerns

One US campaign group, the , is now calling on the US Food and Drug Administration to “move rapidly to approve the vaccination of young boys with the cervical cancer vaccine, to reduce the pool of HPV16 [a particularly aggressive strain]” and protect them from oral cancer.

Walker says however, given the high cost of such a programme, authorities might require more evidence that such a move really would prevent a significant number of male cancers.

Tonsil and throat cancers affect about two in every 100,000 adults in the US and about half a million people around the world each year.

Although, oral cancers linked to HPV infection have risen, the study notes the incidence of oral cancers in parts of the mouth or throat not linked to HPV infection remained constant until 1982, and then started to decline.

Gillison says this is probably due to falling consumption of tobacco and alcohol, which are also linked to the cancers.

Journal reference:

Cancer – Learn more about one of the world’s biggest killers in our comprehensive special report.

SSRIs, or selective serotonin reuptake inhibitors, were supposed to revolutionise care of depression – by treating symptoms without the side effects of older drugs, such as tricyclics.

But despite selling in vast quantities, a new meta-analysis of these drugs, from data presented to the US Food and Drug Administration (FDA), appears to suggest that for most patients they do not work. A previous study had indicated that the benefits of antidepressants might be exaggerated.

UK and US researchers led by of Hull University, UK, studied all clinical trials submitted to the FDA for the licensing of the four SSRIs: fluoxetine (Prozac), venlafaxine, nefazodone, and paroxetine (Seroxat or Paxil), for which full datasets were available.

They conclude that, “compared with placebo, the new-generation antidepressants do not produce clinically significant improvements in depression in patients who initially have moderate or even very severe depression”.

Dishing out drugs

They did detect some benefits in the most severely depressed patients. But conclude that in this group the small effect is “due to decreased responsiveness to placebo, rather than increased responsiveness to medication”.

Given these results, they say that there is little reason to prescribe SSRI medications to any but the most severely depressed patients.

David Healy, a psychiatrist at Cardiff University, UK, specialising in the use of SSRI drugs, says the latest study confirms suspicions that the drugs’ effectiveness had been dramatically overstated.

“Most importantly this new study shows that the people who did respond to the drugs would have responded to placebo, anyway.

“It confirms that GPs should not be dishing these drugs out as first-line treatment for mild depression,” he told ��è����Ƶ. The drugs were, he notes, “routinely being given to people who would get better without them”.

Positive results

Eli Lilly, which manufactures Prozac, says that “extensive scientific and medical experience has demonstrated it is an effective antidepressant”. It adds that: “More than 50 million people with depression have been treated with Prozac since its launch.”

A spokesman for GlaxoSmithKline, which makes Seroxat, points out that the study only looked at a “small subset of the total data available”.

Healy notes however, that drug companies have tended to publish studies showing positive results of the SSRIs in mildly depressed patients.

He says too that there have been concerns that SSRI drugs, particularly paroxetine, may cause dependence in some patients, and this underlines the need to avoid their unnecessary prescription.

Placebo benefit

Healy warns however, that anyone taking SSRI antidepressants should not suddenly stop taking their medication and should consult their doctor before coming off the drugs.

David Nutt, a psychopharmacologist at Bristol University, UK, points out that if SSRIs provided some sort of placebo benefit, this should not be discounted. He notes that “the true drug effect is that of the drug added to that of placebo which is not the same as no treatment”.

Earlier this month, ��è����Ƶ reported claims by US lawyers that they had obtained documents suggesting that an inappropriate analysis of clinical trial data by researchers at GlaxoSmithKline had obscured suicide risks associated with paroxetine for 15 years.

Journal reference: PLoS Medicine

Mental Health – discover the latest research in our continuously updated special report.

A “smart” dashboard that reduces the amount of information displayed to drivers during stressful periods on the road could be available in just five years, say German engineers.

A team from the found they could improve reaction times in real driving conditions by monitoring drivers’ brains and reducing distractions during periods of high brain activity.

They were able to speed up driver’s reactions by as much as 100 milliseconds. It might not sound much, but this is enough to reduce braking distance by nearly 3 metres when travelling at 100 kilometres per hour, says team leader .

“In a real life situation this could be enough to prevent an accident or stop someone being injured, or worse,” he says. “We now have the brain-interface technology to make this a reality.”

Test drives

The researchers used electroencephalograms (EEGs) to measure drivers’ brain activity.

In previous experiments, Müller has shown it is feasible to set up EEG devices that decode only the brain activity generated by concentrating on particular task, such as driving a car. This involves filtering out other signals, including those caused by the random movement of facial muscles.

“This used to take 100 hours. We can now get rid of all the outside ‘noise’ and ‘train’ the device in 20 minutes, thanks to intelligent data analysis methods,” Müller says.

Armed with the technology, his team carried out tests on 12 male and five female drivers in ordinary, non-rush hour conditions on a German highway.

The volunteers were assigned three tasks, each requiring slightly more mental effort, to perform simultaneously. The first task was to drive at 100 km/h. The second, slightly more demanding objective was to hit a button mounted on the left or right of the steering wheel every 7.5 seconds when prompted.

The third task involved firstly counting down in steps of 27 from a randomly generated number between 800 and 900 for two minutes; then focusing on one of two voices played simultaneously inside the vehicle.

Growing distractions

During the experiments EEG electrodes attached to the volunteers’ heads monitored brain activity.

Crucially, when brain activity rose above a predefined threshold, the brain-interface device was rigged up to switch off the secondary task – clicking the steering wheel buttons. Being freed from this task speeded up subjects’ reactions times by an average of 100 milliseconds.

In a real-life situation, such a device might be programmed to switch off superfluous information systems when the drivers’ brain is already over-loaded by other stimuli, such as a conversation with other passengers, says Müller.

The proliferation of in-car technology – such as warning signals, satellite navigation systems, and head-up displays ¬– make driver distraction a pressing issue.

Sticky sensors

Transport expert of University College London, UK, applauds the work.

“This is very interesting research that has shown these sorts of systems can be used,” he told ��è����Ƶ. “It will need to be developed and refined before it can be used practically, but it does suggest some very exciting possibilities in car safety.”

, a brain-computer interface specialist at Essex University, Colchester, UK, says the Berlin group had done “significant work on the detection of movement-related intentions using EEG”, but adds that being able to decode brain signals reliably make take another 10 years at least.

Müller concedes that another major challenge is developing less intrusive EEG equipment. Standard sensors require subjects to be covered in sticky gel and even the newer, dry sensors must be attached all over the head.

In as yet unpublished research, Müller shows that contactless sensors work for electrocardiograms.

“That’s very encouraging,” he says. “But the strength of signal received by an ECG from the heart is 100 times stronger than that received by an EEG, so there’s a lot of development to be done. But I am confident that in five year’s time we will have something.”

A paper describing the work was published in a book late in 2007.

Cars and Motoring – Learn more about the latest technologies in our comprehensive .

The discovery could offer a new target for preventing the spread of AIDS, for example, by incorporating potential inhibitors of the semen chemical into the powerful new microbicides currently being developed to halt the spread of the virus.

While searching for chemicals in semen that could block HIV transmission, an international team led by Frank Kirchhoff at the in Germany, was instead surprised to find that the naturally occurring chemical prostatic acidic phosphatase (PAP) promoted HIV infection.

Closer inspection revealed that PAP formed tiny fibres known as amyloid fibrils that were able to “ferry” the virus into the immune cells that it preys upon.

“Most enhancers have maybe a two or three-fold effect, but here the effect was amazing – more than 50-fold and, under certain conditions, more than 100,000-fold,” says Kirchhoff. “At first, I didn’t believe it, but we ran the experiment over and over, always with the same result.”

Virus ‘ferry’

“The fibrils act like a ferry. They pick the viruses up and then bring them to the cell,” adds fellow researcher Wolf-Georg Forssmann at the , also in Germany.

Significantly, their laboratory tests showed that the fibrils’ ability to assist infection was greatest when the levels of infectious virus were low – resembling the conditions in which sexual HIV-1 transmission usually occurs.

HIV-1, the most common and virulent form of the virus that causes AIDS, has infected about 60 million people and caused over 20 million deaths. Globally, most infections result from genital exposure to the semen of HIV-positive men.

Women who acquire HIV-1 through vaginal intercourse constitute almost 60% of new infections in Africa. Therefore the latest findings could have enormous clinical and public health implications, particularly for regions such as Sub-Saharan Africa where AIDS has caused devastation.

‘Important discovery’

Kirchhoff says he hoped that agents that blocked PAP might be developed and added to vaginal microbicides that women could use to protect themselves from infection. He also believes the discovery could have important implications for researchers hunting an elusive HIV vaccine.

Jonathan Weber, an eminent HIV researcher at Imperial College London, UK, was positive about the findings. “Kirchhoff is a great scientist and this is meticulous work,” he says.

But Weber says there is much work to be done before new microbicides could be produced as a result of the findings. He notes, too, that the ability of HIV-positive women to infect men suggested that the presence of seminal PAP fibrils was not always required for infection to occur.

He adds, however: “This work is exciting because it opens up whole new avenues of prevention. It really does suggest entirely new directions of research, and like many of the really important discoveries it was completely unexpected.”

Journal reference:

HIV and AIDS – Learn more about the worst pandemic in human history in our continuously updated special report.

The American government has poured money into anthrax research since the deadly bacterium was used in attacks in the US in 2001. Mail contaminated with Bacillus anthracis spores killed five people and resulted in enormous clean-up costs.

Vaccines are currently in use, but require up to six doses to be administered, together with annual boosters. This complicated dosing procedure means full compliance is often poor, and increases the risks for those who require protection in difficult situations such as in conflict zones. For people already infected, antibiotic treatment is effective – but only if given quickly enough.

Researchers from and , both in La Jolla, California, US, have now produced a virus-like particle that prevents infection in rats given a dose of anthrax that would normally prove lethal.

Strong immune response

The vaccine, based on the Flock House insect virus, was able to do this after just one dose – a step better than a two-dose nasal vaccine previously developed. The researchers speculate the particle’s ability to display multiple copies of toxin receptors explains its potency.

Each particle of the virus has on its surface 180 copies of a receptor molecule that binds the key toxin produced by B. anthracis. When part of the toxin binds to some of these receptors, the resulting complex provokes a strong immune response.

In rats this caused the animals’ immune system to produce antibodies that later protected them by mopping up anthrax toxin elsewhere.

But the vaccine has another trick up its sleeve. In addition to protecting against anthrax infection, the virus proved effective in treating rats already infected with a potentially deadly dose. In this role, the unfilled receptors on the surface of the virus may snatch toxin molecules before they can do too much damage. All the treated animals survived, while none of the untreated animals did.

‘Highly effective’

The researchers say the treatment might eventually be used in combination with antibiotics. “This recombinant virus-like particle represents a novel and highly effective, dually-acting reagent for treatment and protection against anthrax,” says team leader Anette Schneemann of The Scripps Research Institute.

“Clearly the US Government is keen to find a vaccine that requires fewer doses to boost compliance,” says Phil Luton, an anthrax expert at the UK’s site in Porton Down.

“One that acts as a medication could also be very useful,” Luton says. “We’ll need larger scale studies, though, to see how useful this new treatment actually is.”

Weapons Technology – Keep up with the latest innovations in our cutting edge .

Although both forms of the virus infect humans, HIV-2 goes on to cause AIDS in only 20 per cent of infected people. In contrast, HIV-1, which has spread disastrously through sub-Saharan Africa, goes on to cause AIDS in 98 per cent of people who do not take anti-viral drugs.

A team from Oxford University and the UK (MRC) unit in the Gambia set out to determine why the human immune system is better able to resist HIV-2, which is largely confined to West Africa. Their studies centred on a group of women infected with the virus for over a decade.

They discovered that a tiny part of one viral gene called gag makes HIV-2 vulnerable to attack from the human immune system. What’s more, this gene hardly ever mutates.

The gag gene, which codes for just 18 amino acids, provides a signal for white blood cells, called T-cells, to attack the virus and sweep it out of the blood stream before it can do further damage.

“Clearly there is something special about the gag region – and it looks like vaccine researchers should be focusing on it,” says Aleksandra Leligdowicz who leads the MRC unit. The thinking is that a vaccine containing the right part of the gag gene could trigger the body’s immune response, making it better able to prevent HIV-2 infection developing into full blown AIDS.

Vaccine key

Leligdowicz notes that the two per cent of people infected with HIV-1 who do not progress to AIDS show a strong T-cell response to the gag region as well.

Even more intriguing, most strains of HIV-1 also have a highly-conserved gag gene. The key to better vaccines could be finding just the right part of this region to include, she says.

The findings also indicate that a T-cell based or “cell mediated” defence against HIV is enough to render HIV harmless. For over a decade researchers have argued whether or not an immune response that involved antibodies in addition to T-cells was also vital.

According to Leligdowicz, the latest results suggest it is possible to devise a vaccine to treat HIV, which although not preventing infection or eradicating the virus, will stop the wearing down of the immune system that leads to AIDS.

Virologist who researches HIV vaccines at University College London says. “Ultimately, I think that a vaccine that actually prevents infection will need to make an anti-body response as well as cell-mediated one.

“But the idea of a therapeutic vaccine does have legs. Not only would it treat people, it might make them less able to infect other people, so you would get a double dividend. The study of HIV-2, although a less important pathogen, might well teach us some valuable lessons.”

Journal reference: