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Kidney transplant first for sisters -- Cryofiltration

Kidney transplant first for sisters

Michelle was able to donate a kidney to her sister Maxine

A pioneering procedure has allowed a British woman to get a new kidney from her sister - even though the organ would normally be rejected.

Maxine Bath had been kept alive by dialysis, and had no matching donors in her family.

However, doctors in Coventry used a technique called "cryofiltration" to remove the immune molecules that cause rejection.

Doctors said it could allow more people to undergo transplants.

I'm already feeling healthier - I am looking forward to being able to eat food I couldn't have at all before, like nuts and chocolate Maxine Bath

A total of 927 kidney transplants from "living donors" took place in Britain last year, although thousands more people remain on waiting lists, because a matching donor cannot be found.

Organ rejection happens when the body recognises the new organ as foreign, and the immune system reacts against it.

The risk can be reduced if the donor organ comes from another family member, and patients will often take drugs for the rest of their lives to 'damp down' their immune response.

However, Maxine, 41, from Wolverhampton, who had been in kidney failure for 15 years, was found to have immune system antibodies against the tissue types of all her family members, which seemed to rule them out as "living donors".

Other ways of removing these antibodies could not be used, as she had low blood pressure, and they could lower it further.

However, the new technique of cryofiltration did not present the same risk, and this is believed to be the first time it has been used to help a patient receive a non-matched organ.

The procedure involves circulating the blood plasma through a machine which heavily chills it, turning proteins and antibodies into a gel-like substance which can then be easily filtered out, before the plasma is re-warmed and returned to the patient.

Race against time

Dr Rob Higgins, a kidney specialist at University Hospitals Coventry and Warwickshire NHS Trust said: "Maxine would have gone blind within two years because of her low blood pressure, if she had not received a new kidney.

"This is another innovative measure we have implemented at the trust which opens the doors of donation for more kidney patients awaiting transplants."

Both Maxine, and her sister Michelle, who was the closest match available in the family, underwent the procedure five times before the transplant took place.

The operation, carried out in November, has already transformed Maxine's life.

She said: "I'm already feeling healthier - I am looking forward to being able to eat food I couldn't have at all before, like nuts and chocolate.

"Rob told me I was the first kidney patient in the world to try this technique which I thought was really exciting - it hasn't sunk in yet."

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Bank of America sued over Merrill Lynch bailout

Bank of America is the latest US bank to report

Legal action has begun against Bank of America and its former bosses, accusing them of duping investors and taxpayers during the takeover of Merrill Lynch.

The defendants are accused of intentionally withholding details of huge losses Merrill was suffering.

New York state officials have filed the action against the bank, former chief executive Kenneth Lewis and former chief financial officer Joseph Price.

Bank of America said the charges were "regrettable" and lacked merit.

"The evidence demonstrates that Bank of America and its executives, including Ken Lewis and Joe Price, at all times acted in good faith and consistent with their legal and fiduciary obligations," a spokesman said.

He added that US financial watchdog the Securities and Exchange Commission (SEC) had access to the same evidence as New York state officials and had found no basis to bring charges.

After the Merrill bailout, Bank of America received $45bn (£28.5bn) in government funds.

'Arrogant scheme'

According to the lawsuit, the accused withheld the full details of Merrill's financial strife in order that its shareholders would approve the merger.

They had then "manipulated" the federal government by claiming they would back out of the deal unless US bailout funds were received, it was alleged.

"This merger is a classic example of how the actions of our nation's largest financial institutions led to the near-collapse of our financial system," said New York State attorney general Andrew Cuomo.

"Bank of America, through its top management, engaged in a concerted effort to deceive shareholders and American taxpayers at large.

"This was an arrogant scheme hatched by the bank's top executives who believed they could play by their own set of rules. In the end, they committed an enormous fraud and American taxpayers ended up paying billions for Bank of America's misdeeds."

Earlier on Thursday, the SEC said Bank of America had agreed to pay $150m to settle complaints over its handling of the merger.

Last month Bank of America reported a net loss of $194m in the last three months of 2009. That compared with a loss of $1.8bn in the same period a year earlier.

It added that it had repaid the $45bn government bailout money it had received but, taking the impact of this into account, it made a loss of $5.2bn.

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Close encounters with Japan's 'living fossil'

By Richard Black Environment correspondent, BBC News

Dr Takeyoshi Tochimoto gives a guided tour of the world's biggest amphibian

It soon becomes clear that the giant salamander has hit Claude Gascon's enthusiasm button smack on the nose.

"This is a dinosaur, this is amazing," he enthuses.

"We're talking about salamanders that usually fit in the palm of your hand. This one will chop your hand off."

As a leader of Conservation International's (CI) scientific programmes, and co-chair of the Amphibian Specialist Group with the International Union for the Conservation of Nature (IUCN), Dr Gascon has seen a fair few frogs and salamanders in his life; but little, he says, to compare with this.

The skeleton of this species is almost identical to that of the fossil from 30 million years ago; therefore it's called the 'living fossil' Dr Takeyoshi Tochimoto

Fortunately for all of our digits, this particular giant salamander is in no position to chop off anything, trapped in a tank in the visitors' centre in Maniwa City, about 800km west of Tokyo.

But impressive it certainly is: about 1.7m (5ft 6in) long, covered in a leathery skin that speaks of many decades passed, with a massive gnarled head covered in tubercles whose presumed sensitivity to motion probably helped it catch fish by the thousand over its lifetime.

If local legend is to be believed, though, this specimen is a mere tadpole compared with the biggest ever seen around Maniwa.

A 17th Century tale, related to us by cultural heritage officer Takashi Sakata, tells of a salamander (or hanzaki, in local parlance) 10m long that marauded its way across the countryside chomping cows and horses in its tracks.

The hanzaki shrine is an attempt to make up for a mythical killing

A local hero was found, one Mitsui Hikoshiro, who allowed the hanzaki to swallow him whole along with his trusty sword - which implement he then used, in the best heroic tradition, to rend the beast from stem to stern.

It proved not to be such a good move, however.

Crops failed, people started dying in mysterious ways - including Mr Hikoshiro himself.

Pretty soon the villagers drew the obvious conclusion that the salamander's spirit was wreaking revenge from beyond the grave, and must be placated. That is why Maniwa City boasts a shrine to the hanzaki.

The story illustrates the cultural importance that this remarkable creature has in some parts of Japan.

Its scientific importance, meanwhile, lies in two main areas: its "living fossil" identity, and its apparently peaceful co-existence with the chytrid fungus that has devastated so many other amphibian species from Australia to the Andes.

Close family

"The skeleton of this species is almost identical to that of the fossil from 30 million years ago," recounts Takeyoshi Tochimoto, director of the Hanzaki Institute near Hyogo.

"Therefore it's called the 'living fossil'."

The hanzaki (Andrias japonicus) only has two close living relatives: the Chinese giant salamander (A. davidianus), which is close enough in size and shape and habits that the two can easily cross-breed, and the much smaller hellbender (Cryptobranchus alleganiensis) of the south-eastern US.

Creatures rather like these were certainly around when dinosaurs dominated life on land, and fossils of the family have been found much further afield than their current tight distribution - in northern Europe, certainly, where scientists presumed the the lineages had gone extinct until tales of the strange Oriental forms made their way back to the scientific burghers of Vienna and Leiden a couple of centuries ago.

"They are thought to be extremely primitive species, partly due to the fact that they are the only salamanders that have external fertilisation," says Don Church, a salamander specialist with CI.

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Scientists at the Hanzaki Insitute filmed a fight between two of the giant beasts

The fertilisation ritual must be quite some sight.

Into a riverbank den that is usually occupied by the dominant male (the "den-master") swim several females, and also a few other males.

The den-master and the females release everything they have got, turning incessantly to stir the eggs and spermatozoa round in a roiling mass.

Maybe the lesser males sneak in a package or two as well; their function in the ménage-a-many is not completely clear.

They have bacteria living on their skin that produce peptides that are lethal to the amphibian chytrid fungus Don Church, Conservation International

When the waters still, everyone but the den-master leaves; and he alone guards the nest and its juvenile brood.

It is not an ideal method of reproduction.

Research shows that genetic diversity among the hanzaki is smaller than it might be, partly as a result of the repeated polygamy, which in turn leaves them more prone to damage through environmental change.

But for the moment, it seems to work.

Outside the breeding season, the salamander's life appears to consist of remaining as inconspicuous as possible in the river (whether hiding in leaves, as the small ones do, or under the riverbanks like their larger fellows) and snapping whatever comes within reach, their usual meandering torpor transformed in an instant as the smell of a fish brushes by.

The adults' jaws are not to be treated lightly.

Among Dr Tochimoto's extensive collection of photos is one of bloodied human hands; and as he warns: "you may be attacked and injured; please be careful".

The giant Maniwa hanzaki brought gasps from experienced amphibian-watchers

When the chytrid fungus was identified just over a decade ago, indications were that Japan would be an unlikely place to look for its origins.

With the discovery of chytrid on museum specimens of the African clawed frog (Xenopus laevis), an out-of-Africa migration spurred by human transportation of amphibians once seemed the simple likelihood.

But just last year, a team of researchers led by Koichi Goka from Japan's National Institute for Environmental Studies published research showing that certain strains of chytrid were present on Japanese giant salamanders, and only on Japanese giant salamanders, including museum specimens from a century or so back; and that the relationship seemed benign.

AMPHIBIANS: A QUICK GUIDE First true amphibians evolved about 250m years ago There are three orders: frogs (including toads), salamanders (including newts) and caecilians, which are limbless Adapted to many different aquatic and terrestrial habitats Present today on every continent except Antarctica Many undergo metamorphosis, from larvae to adults

The hanzaki-loving strains of chytrid appear to differ from those that are proving so virulent to amphibians now.

Unravelling all that, says Don Church, might tell us something about the origins and spread of chytrid - and there is so much diversity among Japanese chytrid strains that the country is now being touted as a possible origin, as diversity often implies a long evolutionary timeframe.

More importantly, the discovery might also provide options for treating the infection.

"In the case of the North American salamanders, what was found was that they have bacteria living on their skin that produce peptides that are lethal to the amphibian chytrid fungus," says Dr Church.

"And those bacteria might be able to be transplanted to other species that can't fight off the fungus."

This is a line of research that is very much in play in laboratories around the world.

It appears likely now that studies of the Japanese giant salamander can expand the number of chytrid-fighting bacteria known to science, and so extend the options for developing treatments for an infection that currently cannot be controlled in the wild.

But that can only come to pass if the giant salamanders endure; something that is not guaranteed, with the challenges they face in modern Japan including, perhaps, new strains of chytrid itself.

There is as yet no modern hero able to still the pace of habitat loss or prevent invasion from rival species.

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Commentary

There is a word that defines the observation being seen here known as stasis. The observation I'm talking about is where creatures that are millions of years old, stay virtually the same in our fossil record as time goes by.

If you look at our fossil record actually creatures appear out of nowhere and stay virtually the same for millions of years. A good number of scientists believe there are no transitions, just people making non scientific leaps of faith.

Since when was science about taking leaps of faith?

Stasis is a very common phenomenon in the fossil record and the most damning proof that Darwin, who thought cells were empty blobs of gue, was wrong.

Vegetative state patients can respond to questions

By Fergus Walsh Medical correspondent, BBC News

Dr Adrian Owen, co-author of the research: "This changes things"

Scientists have been able to reach into the mind of a brain-damaged man and communicate with his thoughts.

The research, carried out at in the UK and in Belgium, involved a new brain scanning method.

Awareness was detected in three other patients previously diagnosed as being in a vegetative state.

The study in the New England Journal of Medicine shows that scans can detect signs of awareness in patients thought to be closed off from the world.

Patients in a vegetative state are awake, not in a coma, but have no awareness because of severe brain damage.

Scanning technique

The scientists used functional magnetic resonance imaging (fMRI) which shows brain activity in real time.

They asked patients and healthy volunteers to imagine playing tennis while they were being scanned.

In each of the volunteers this stimulated activity in the pre-motor cortex, part of the brain which deals with movement.

This also happened in four out of 23 of the patients presumed to be in a vegetative state.

The BBC's Fergus Walsh tests the new brain scanning technique

I volunteered to test out the scanning technique.

I gave the scientists two women's names, one of which was my mother's.

I imagined playing tennis when they said the right name, and within a minute they had worked out her name.

They were also able to guess correctly whether I had children.

Questions

This is a continuation of research published three years ago, when the team used the same technique to establish initial contact with a patient diagnosed as vegetative.

But this time they went further.

With one patient - a Belgian man injured in a traffic accident seven years ago - they asked a series of questions.

He was able to communicate "yes" and "no" using just his thoughts.

The team told him to use "motor" imagery like a tennis match to indicate "yes" and "spatial" imagery like thinking about roaming the streets for a "no".

The patient responded accurately to five out of six autobiographical questions posed by the scientists.

For example, he confirmed that his father's name was Alexander.

The study involved scientists from the Medical Research Council (MRC), the Wolfson Brain Imaging Centre in Cambridge and a Belgian team at the University of Liege.

Dr Adrian Owen from the MRC in Cambridge co-authored the report:

"We were astonished when we saw the results of the patient's scan and that he was able to correctly answer the questions that were asked by simply changing his thoughts."

Dr Owen says this opens the way to involving such patients in their future treatment decisions: "You could ask if patients were in pain and if so prescribe painkillers and you could go on to ask them about their emotional state."

It does raise many ethical issues - for example - it is lawful to allow patients in a permanent vegetative state to die by withdrawing all treatment, but if a patient showed they could respond it would not be, even if they made it clear that was what they wanted.

The Royal Hospital for Neurodisability in London is a leading assessment and treatment centre for adults with brain injuries.

Helen Gill, a consultant in low awareness state, welcomed the new research but cautioned that it was still early days for the research: "It's very useful if you have a scan which can show some activity but you need a detailed sensory assessment as well.

"A lot of patients are slipping through the net and this adds another layer to ensure patients are assessed correctly."

She said the hospital did a study of 60 patients admitted with a diagnosis of vegetative state and 43% could communicate.

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Journal stem cell work 'blocked'

By Pallab Ghosh Science correspondent, BBC News

Billions of pounds of public money is spent on stem cell research

Stem cell experts say they believe a small group of scientists is effectively vetoing high quality science from publication in journals.

In some cases they say it might be done to deliberately stifle research that is in competition with their own.

It has also emerged that 14 leading stem cell researchers have written an open letter to journal editors in order to highlight their dissatisfaction.

Billions of pounds of public money is spent on funding stem cell research.

The open letter to the major scientific journals claims that "papers that are scientifically flawed or comprise only modest technical increments often attract undue profile. At the same time publication of truly original findings may be delayed or rejected".

Two internationally-renowned researchers have spoken to BBC News about their concerns.

They are Robin Lovell-Badge, from the National Institute for Medical Research (NIMR), and Austin Smith, from the University of Cambridge.

Professor Lovell-Badge said: "It's turning things into a clique where only papers that satisfy this select group of a few reviewers who think of themselves as very important people in the field is published.

It's an editor's responsibility to ensure that delays are minimised, and we stop using any referee where a pattern of delays is apparent Philip Campbell, Nature

"You can get a lot of hype over a paper published on stem cell research that's actually a minimal advance in knowledge whereas the poor person that is doing beautiful research that is not catching the eye of the editor, you don't get to hear about that, even though it could be the world changing piece of research."

The issue is important because billions of pounds of public money are spent on funding stem cell research internationally. The funding is directed largely towards groups and individuals who have had their research published in the top journals. So if the journals are getting it wrong then public money is going to waste.

Dr Philip Campbell, the editor of Nature, which is one of the leading journals in the field, said: "Last year we used about 400 reviewers in stem cell and developmental biology, and we constantly recruit new referees. The idea that there's some privileged clique is utterly false."

It is a requirement of publicly funded research to publish in scientific journals.

This process involves sending a report of the research to an editor at a journal.

If the editor deems it sufficiently novel and interesting, they will ask two or three scientists who are experts in the field to review the research and send in comments.

It is at this stage where scientists who may well be rivals of the person who submitted their research say whether the research is good or bad. They can also suggest to the journal editor that more experiments need to be carried out in order to justify the conclusions of the research.

'Extra experiments'

The journal editor decides to publish the research paper usually when the majority of reviewers are satisfied. But professors Lovell-Badge and Smith believe that increasingly some reviewers are sending back negative comments or asking for unnecessary experiments to be carried out for spurious reasons.

In some cases they say it is being done simply to delay or stop the publication of the research so that the reviewers or their close colleagues can be the first to have their own research published.

"It's hard to believe except you know it's happened to you that papers have been held up for months and months by reviewers asking for experiments that are not fair or relevant," Professor Smith said.

Dr Campbell denies this as far as his journals are concerned: "It's an editor's responsibility to ensure that delays are minimised, and we stop using any referee where a pattern of delays is apparent, whatever the reason might be."

We are seeing the publication of a lot of papers in high profile journals with minimal scientific content or advance Robin Lovell-Badge, NIMR

These kinds of allegations are not new and not confined to stem cell research. But professors Smith and Lovell-Badge believe that the problem has become particularly acute in their field of research recently for two reasons.

Firstly, research grants and career progression are now determined almost entirely by whether a scientist gets published in a major research journal. Secondly, in stem cell science, hundreds of millions of pounds are available for research - and so there is a greater temptation for those that want the money to behave unscrupulously.

"The problem has become more common and more serious now," said Professor Smith.

"The issue here is all about public funding because you have to get these papers published to be able to get your next grant. It could be worth half a million pounds. It can be difficult for people in that position to be objective."

Even if research is not being deliberately stifled, high quality work is being overlooked as an "accidental consequence of journal editors relying too much on the word of a small number of individuals", according to Professor Lovell-Badge.

"You will have what looks like a very good paper by a very reputable scientist - but the journal takes the word of one particular reviewer too strongly. They have their favourite reviewers and what this means is that it distorts what gets published because that's going to be the view of one individual which may not reflect where the field should be going," he said.

Practical obstacles?

Dr Campbell says that as far as his journals are concerned the charge is untrue: "Our editors, who frequently attend conferences and visit laboratories in order to keep abreast of the field and the people in it, have always used their own judgement in what we publish. We have not infrequently overruled two or even three sceptical referees and published a paper."

But at a recent stem cell scientific meeting, 14 of the world's leading stem cell researchers said that journal editors hadn't seen through what they described as "unreasonable or obstructive" reviews. In an open letter to the journals, they proposed that if a paper was published, the accompanying reviews should be provided as supplementary material online.

Dr Campbell said that he was sympathetic to the idea although he envisaged practical obstacles. Professor Lovell-Badge believes that the journal editors could do more to identify bias in the review process.

"Editors should be able to see when reviewers are asking for unnecessary experiments to be carried out and if it's the difference between an opinion of the referee and a factual problem. But what tends to happen is that the editor takes the opinion of an editor rather than the factual substance," he said.

One of the main reasons for this, according to Professor Smith, is that journals are in competition. Editors have become dependent on favoured experts who both review other people's stem cell research and submit their own papers to the journal. If the editor offends these experts, they may lose future papers to a rival.

This is leading to the journals publishing mediocre science, according to Professor Lovell-Badge.

"We are seeing the publication of a lot of papers in high profile journals with minimal scientific content or advance, and this is partly because of these high-profile journals needing to keep their so called 'impact factors' as high as possible. That's determined by the number of citations that the papers have and they know that some of this trendy work is going to get cited and they seem not to care about whether its a real scientific advance or not," he said.

Commenting on the allegations, Monica Bradford, executive editor of Science, another major journal, said: "Our current policy is to preserve the confidentiality of reviewers' names and comments. Some journals have tried experiments to test the impact of open review on the quality of the feedback received through peer review.

"We have not been convinced to switch to such a system, but we will continue to monitor such experiments. We also will discuss the pros/cons of our current process internally and with our senior editorial board.

"We do recognise that human factors such as competition and potential financial gains can bias a reviewer's assessment of a paper and we expect our editors to consider these factors when evaluating the comments of the reviewers, particularly in cutting-edge areas of research."

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