Crippling and long-lasting fatigue is one the most common side-effects of chemotherapy. The new work indicates that acupuncture can boost energy levels and radically improve a patient’s quality of life.

Numerous trials have shown that acupuncture appears to work for a variety of conditions. Last year, two studies demonstrated that acupuncture may help boost fertility after IVF, although a third study failed to demonstrate an effect. The US National Institutes of Health says that acupuncture is an effective treatment for nausea caused by anaesthesia and cancer chemotherapy, as well as dental pain following surgery.

In the latest study, 47 patients suffering from moderate to severe fatigue were enrolled in a randomised placebo-controlled trial at Manchester’s Christie Hospital. The patients were randomly assigned to one of three groups to receive either acupuncture or acupressure – placing physical pressure on acupuncture points with hands or objects – or sham acupressure.

Quality of life

“People felt better and had more energy after the acupuncture,” says , professor of cancer and supportive care at the University of Manchester who led the work.

“Patients had the energy to walk to the shops and to socialise, so their quality of life improved significantly,” he says.

The acupuncture group received six 20-minute sessions spread over three weeks. During these sessions the characteristic thin needles were inserted about 2 centimetres into the patients’ body at three points. The points were selected for their supposed propensity to boost energy levels and reduce fatigue.

Patients in the acupressure group were taught to massage the same acupuncture points for one minute a day for two weeks. The sham acupressure group was taught the same technique, but told to massage different points on the body not associated with energy and fatigue.

Patients in the acupuncture group reported a 36% improvement in fatigue levels, whilst those in the acupressure group improved by 19%. Those in the sham acupressure group reported a 0.6% improvement.

Needle mystery

Molassiotis says that the improvements were not down to the placebo effect. “Our trial was able to take this into account,” he says. But he says a bigger trial is needed to properly characterise the effect and is planning one in the near future.

Nobody is sure how acupuncture actually works, but researchers have previously suggested that it might reduce fatigue by stimulating the body to release endorphins – morphine-like chemicals that block pain signals and induce a feeling of well-being.

Kat Arney, of Cancer Research UK, welcomes the new findings but is more cautious about their significance.

“This was a very small study and bigger randomised controlled trials are needed before we know for sure if acupuncture or acupressure is effective at relieving some of the side effects of cancer therapy,” she says.

Journal reference: ()

“In our trial we had patients completely paralysed on one side of their body who returned to normal almost immediately after the clot was retrieved,” says Sidney Starkman, of the Stroke Center at the University of California at Los Angeles. “How often do you get a chance to reverse a patient’s stroke on the operating table?”

Starkman’s team are evaluating the new device, which is made by California-based company Concentric Medical, and it has been tested on 114 patients so far. Blood flow was restored to the affected parts of the brain in 61 patients. Of these, 23 ended up with either no disability or with only relatively minor problems, such as difficulty writing.

Strokes are now the second biggest killer in the developed world and the largest cause of disability. Over 600,000 people a year in both the US and the European Union suffer a stroke caused by a blood clot, accounting for substantial proportion of all spending on health care.

“Clearly if there was an effective treatment then the public health benefits would be very high,” says Peter Rothwell, director of the Stroke Prevention Research Unit at Oxford University, UK.

Clot busters

Most strokes are caused when a clot seals off a blood vessel supplying the brain, causing part of the brain to be starved of oxygen. Unless treated swiftly, the affected brain tissue dies, resulting in death or permanent disablement. Strokes are currently treated in two ways, both of which use “clot-busting” drugs to unblock the arteries. The most straightforward treatment involves the injection of plasminogen activator (tPA) into a main artery, which encourages the clot to dissolve.

Another approach involves guiding a catheter to the site of the clot and spraying it directly with tPA. The blood-clot can also be prodded with the catheter tip to help break it up.

But the new device aims to remove the clot completely. The spiral-tipped catheter looks like a miniature corkscrew, 2.6 millimetres wide. It is inserted into an artery in the groin and guided to the blocked blood vessel near the brain using a real-time X-ray scanner. It is then drilled into the clot, just as a corkscrew is driven into the cork of a wine bottle.

Inflated balloon

Next, a balloon is inflated immediately behind the tip of the device. This temporarily seals off the blood flow, reducing the force needed to pull out the clot.

Once it is moving, the clot is pulled back into a larger catheter and the whole device is removed from the body. The blood flow returns to the damaged part of the brain within seconds.

Starkman says the main advantage of the new device is that it does away with the need for clot-busting drugs. About six per cent of patients given such drugs suffer a brain haemorrhage. “Once the bleeding starts the patient is likely to end up either dead or disabled. It’s catastrophic,” he says.

Clot-busting drugs are also only effective if given within a few hours of the stroke. The patients in Starkman’s trial suffered strokes at least eight hours before their treatment began.

The new work is being presented at the American Stroke Association’s conference in San Diego, California, on Thursday.

The dangerous toxin was found in a letter addressed to Bill First, the right wing leader of the Republican party in the Senate. The Senate was also targeted by series of bioterror attacks in 2001, when anthrax was sent by mail.

The powder was found shortly after 2000 GMT in a mail room serving the Senate. A bioterror “field test” for chemical and biological agents indicated that the powder was ricin. A second, more reliable test produced the same result. The outcome of a more detailed analysis will be released later on Tuesday.

Sixteen people have been decontaminated but are they not thought to be at risk of injury. Senator Bill Frist said: “There is no cause for alarm. Nobody’s been hurt and everybody is fine.” Three buildings have been closed and all public tours cancelled, but the Senate will meet as usual.

Tiny dose

Another letter containing ricin was discovered at a postal distribution centre at an airport in South Carolina in October 2003. Police believe the letter was sent in protest against new regulations for commercial truck drivers.

Ricin is deadly in tiny doses – as little as 70 microgrammes can kill a person. But it is relatively easy to make from the beans of the castor plant, requiring only low-tech equipment and commonly available solvents. Instructions on how to make the poison can be quickly found on the internet.

Ricin must be inhaled, ingested or injected to take effect. Consequently, security experts believe it would be difficult to mount a mass terrorist attack using the compound.

However, the poison was used to assassinate the Bulgarian defector Georgi Markov in London in 1978. He was injected using the point of an umbrella and died within four days.

The symptoms of ricin poisoning are similar to flu, including a high temperature and loss of appetite. Death usually follows within four days, and there is no antidote.

The antibody was uncovered after researchers at the Dana-Farber Cancer Institute in the US screened 27 billion candidates in less than two months.

Jianhua Sui, one of the study’s authors, told ��è����Ƶ. “We hope a treatment will be tested in people by next winter. Our antibodies are human in origin so they should be well tolerated by patients. Human antibodies also have a long track record of safety so we don’t envisage any major problems.”

Virologists have welcomed the potential treatment. “This could be a very useful therapy especially for those most at risk such as health care workers,” says John Oxford, from the Queen Mary School of Medicine in London, UK. “SARS has a long incubation period so you will have quite a good chance of stopping the disease in time.”

The antibodies are the latest in of a string of proposed treatments to be put forward, but none has yet been demonstrated to be effective in humans. Many patients were treated with an anti-viral drug called Ribavirin during the 2003 epidemic but it was only partially successful. Test tube studies have also suggested beta interferon and even a liquorice root extract called glycyrrhizin could be effective.

As with the treatments, no vaccine has yet shown effectiveness in people, but Chinese scientists are planning preliminary safety trials in humans.

Microbial factories

The Dana-Farber team reasoned that an antibody capable of sticking to the spike protein would have a good chance of destroying the virus’s infectivity. To identify such a protein, the team screened the Cancer Institute’s enormous library of antibodies. The library was created in the lab from human B cells and is similar in principle to the way the immune system creates, selects and amplifies its own antibodies.

The antibodies were first created by extracting the mRNA from B cells and reverse transcribing them into DNA. These genes were then inserted into bacteria, transforming the microbes into factories that churned out complexes coated with a unique antibody.

Solutions containing millions of different complexes were then passed through columns impregnated with the SARS spike protein. Antibodies that stuck to the spike protein were identified and the bacteria were used again to manufacture promising antibodies in large amounts.

Eureka moment

“It was one of those ‘eureka’ experiences,” said Wayne Marasco, another team member. “It was pretty dramatic.” Early tests in rodents suggest 80R is effective in animals too.

The team now hopes to test the antibody in human volunteers. If it is effective, it could provide “passive” immunity for a few weeks or even months. Such a treatment would be extremely useful in any future epidemic that breaks out before a vaccine is developed and implemented.

The success of the study is also important in another, more general way, believes Marasco: “This work is really a proof of principle for responding to emerging infectious diseases. If the international community works together, it can make a serious dent in the time it takes to develop protective treatments against these threats.”

Journal reference : Proceedings of the National Academy of Sciences (DOI: 10.1073/pnas.0307140101)

Such transmission has been feared by health authorities, as it could signal the start of a dangerous new phase in the epidemic. However, there is so far no evidence that the virus has undergone changes that would make it highly contagious among humans. The greatest fear is that the bird flu will recombine with a human strain, making it both highly pathogenic and easily transmitted from person to person.

Klaus Stöhr, head of influenza surveillance at the WHO, points out that some human-to-human transmission took place when the same type of bird flu virus, H5N1, first infected humans in Hong Kong in 1997.

Another bird flu virus, H7N7, spread between people in the Netherlands in 2003. In both cases the second person to get the virus did not pass it on to a third. That also seems to be what happened in Vietnam, says Stöhr.

Wedding feast

The WHO revealed on Sunday that two Vietnamese women who died from bird flu may have been infected at a wedding. A 31-year-old man and his sister died shortly afterwards.

The man and his sister had both slaughtered and prepared a duck for the wedding reception. Another sister, and the man’s wife, aged 23 and 30, also went on to develop the disease, and the wife died. But neither is known to have had contact with poultry.

“The investigation failed to reveal a specific event such as contact with infected poultry or an environmental source that might explain the source of infection,” said a WHO spokesman. “The WHO considers that limited human-to-human transmission is one possible explanation.”

In a separate development, a woman in Germany was admitted to hospital in Hamburg on Monday suffering from suspected bird flu. The woman had recently returned from a holiday Thailand.

“We are now running a PCR test on her to see whether we can identify whether she has the flu virus or not,” says Bernhard Fleischer, director of the Bernhard Nocht Institute for Tropical Medicine. But he told ��è����Ƶ: “At this stage its rather premature to fear that she has flu.”

If the tests do prove positive, investigators will want to determine whether the tourist had contact with any poultry or is more likely to have caught it from another person.

Widening epidemic

The known extent of the bird flu epidemic widened on Sunday, when the Chinese authorities announced another five provinces in which there are suspected outbreaks. These included outbreaks on the east coast near Shanghai, and in the remote western province of Xinjiang, both far from the duck farm in the south-east of the country which was the first outbreak to be confirmed. There have now been 14 suspected and confirmed outbreaks in China.

On 28 January, ��è����Ƶ reported that bird flu might be circulating more widely in China than had been stated. There were human cases of an H5N1 virus in China in 2003, and the virus was also discovered in Chinese duck meat in 2001 and 2003. On 30 January, China announced confirmed outbreaks of bird flu in two provinces where the disease had not previously been reported.

China has also announced another confirmed case of SARS, the fourth human case since the 2003 epidemic ended. The 40-year-old doctor is from the Guangdong province, where the 2003 epidemic that claimed 800 lives began.

He developed symptoms on 7 January and has now made a full recovery. But the WHO – which was only informed on 30 January – criticised the delay in releasing the information.

“They are of enormous benefit for such things as early cancer detection, but medical experts need to be aware of the quantifiable risks of X-rays.” says Amy Berrington, of Oxford University, UK, and one of the research team. “If you need an X-ray for medical reasons then I should not worry about it.”

But Peter Herzog, of Ludwig-Maximilians University in Munich, Germany, points out that many X-rays may be unnecessary. In some countries, up to a third of chest X-rays may not be required, he says. “In everyday practice, those ordering radiological procedures should think carefully about the benefits and risks to their patients for each examination.”

Adrian Dixon, a radiologist and spokesman for the Royal College of Radiologists, believes this already happens in the UK: “This study validates our policy. Our members are very scrupulous about vetting all requests for X-rays and will only carry them out if it is for the benefit of the patient.”

Medical X-rays are the biggest source of man-made radiation exposure and are being used with increasing frequency in many countries. In the US, for example, their use has increased by 20 per cent since the early 1980s. The growing use of CT (computed tomography) scans, which also use X-rays, are also adding to exposure.

Global variations

This rise prompted Berrington, with colleague Sarah Darby, to update the seminal 1981 Dole and Peto study of the risks posed by medical X-rays. Dole and Peto estimated that 0.5 per cent of all deaths from cancer in the US were attributable to medical X-rays.

The Oxford team first estimated the radiation dose received by patients for each X-ray. They then collated the numbers of X-rays performed each year in 15 developed nations.

This data was then fed into a computer model for estimating the risks posed by ionising radiation. This “Excess Relative Risk Model” is derived from data gleaned from Japanese atomic bomb survivors.

The authors found substantial world-wide variations in the numbers of cancers attributable to X-rays. The UK had the lowest, with 0.6 per cent of all cancers attributable to medical X-rays. About 0.9 per cent of all cancers in the US are caused by X-rays.

But in Japan, the corresponding figure was 3.2 per cent. Overall, Berrington and Darby estimate that X-ray-based medical imaging causes an extra 18,500 cases of cancer each year across the 15 countries studied.

Herzog cautions that the increased risk of cancer could have been over-estimated by the study, because of its reliance on the data from Japanese atomic bomb survivors. It is the most accurate data available, but the survivors were exposed to many types of radiation, not just X-rays alone.

Journal reference: The Lancet (vol 363, p 345)

“At the two extremes we looked at, the dietary changes increased the difference in lifespan by more than 50 per cent,” says Susan Ozanne, who performed the research with Nicholas Hales at Cambridge University, UK.

“In humans, this could equate to the difference between reaching 50 and living to be 75 years old,” she says. The research joins existing evidence that maternal diets in humans can have a life-long impact.

The researchers fed a variety of different diets to a group of 144 mice pups, as well as their mothers. The pups that lived longest were well fed in the womb and had mothers whose diets were relatively low in protein during lactation. Their lifespans were further enhanced if they were not given a “junk food” type diet, rich in sugar and fat.

The pups that had the shortest lives received a low-protein diet while in the womb, but were subsequently fed well by their mothers who ate a protein-rich diet whilst breast feeding. Their lifespans were further shortened if they ate junk food after weaning. Overall the research indicates that being well fed in the womb and during infancy helps mice resist the ill-effects of a junk food diet later.

Calorific value

There is substantial evidence that restricting the calories in a diet extends lifespan. But although the diets fed to the mice contained different levels of protein, sugar and fat, Ozanne and Hales did not assess the calorific value. “We do not know in mice whether the calorie intake was the same, but when we looked at it in rats it was,” Ozanne told ��è����Ƶ.

If the conclusions of the animal study turn out to be applicable to humans, it would have implications for women who choose not to breast feed, Ozanne believes.

Formula milk is often richer than human milk and mothers also tend to over feed bottle-fed babies. If this were combined with a baby being premature or under-weight, the situation would resemble that of the shortest lived mice pups.

David Finkelstein, of the US National Institute on Aging, told ��è����Ƶ that the results of the study were “very intriguing”.

“It is known that if you starve animals of calories while they are still in the womb then they can suffer from diabetes. The damage that’s done in utero appears to be permanent,” he says. “But the truth is, everything that we know about the effects of calorie restriction diets can be put on the head of a pin.”

Journal reference: Nature (vol 427, p 411)

The disease closely resembles Alzheimer’s, Parkinson’s and senile dementia, but appears to be caused by a genetic defect linked to fragile X syndrome. Until now carrying the defect was not thought to be harmful.

Researchers believe the new disease, named FXTAS (fragile X-associated tremor/ataxia syndrome), may affect up to one in 3000 men, with most sufferers being over 50 years old.

“FXTAS may be one of the most common causes of tremor and balance problems in the adult population and yet it is being misdiagnosed,” says Paul Hagerman, a biochemist at the University of California, Davis and one of the research team. “Thankfully it can now be identified with a standard DNA test.” “Many of the patients we studied were thought to have Parkinson’s disease, Alzheimer’s, or were just suffering from normal ageing,” he told ��è����Ƶ. “In some cases patients with the disease even had surgery. Now that FXTAS has been identified these people will no longer receive the wrong treatment.”

Repeated mistake

Fragile X syndrome is the most common cause of inherited mental retardation and affects one in 3600 boys and about one in 5000 girls. It is caused by a mutation in the FMR1 gene, which codes for a protein that helps maintain the health of nerve cells in the brain.

When a particular segment of DNA in the FMR1 gene is repeated too many times the resulting protein fails to function correctly. Unaffected people have about 30 CGG repeats in their FMR1 gene, but carriers have between 55 and 200 repeats. Male carriers pass on this “premutation” to their daughters, who in turn run a high risk of having children with fragile X syndrome.

It had been thought that carriers of the premutation were spared any ill effects. But anecdotal evidence that some grandfathers of children with Fragile X were prone to dementia alerted the researchers. In the new study they compared almost 200 men who were part of families with Fragile X with 60 controls.

They found having the premutation correlated with a much higher risk of neurodegenerative symptoms, with, for example, almost 40 per cent of men in their sixties affected.

Abnormal material

FXTAS is characterised by tremors, balance problems and dementia that become increasingly severe with age. Initial signs of the disorder include difficulty writing, using eating utensils, pouring water and walking. Other features include short-term memory loss and anxiety.

The discoverers of FXTAS are unsure about how the premutation in the FMR1 gene causes the disease. But tissue and postmortem studies of brains from FXTAS patients show accumulations of abnormal cellular material in the nuclei of brain cells throughout the cortex and brainstem regions.

“This offers an important clue about the cause of the disorder, one that may ultimately help with the development of therapies,” says Hagerman.

Journal reference: Journal of the American Medical Association, 27 January 2004

The modified nanotubes have so far only been used to ferry a small peptide into the nuclei of fibroblast cells. But the researchers are hopeful that the technique may one day form the basis for new anti-cancer treatments, gene therapies and vaccines.

“Our research is still in its earliest stages, but it shows great promise,” says Alberto Bianco, at the CNRS Institute in Strasbourg, France. “The nanotubes seem to migrate mainly to the nucleus, so we can imagine them being used to deliver gene constructs.”

“We can also imagine them being used to deliver drugs to specific compartments of the cell,” he told ��è����Ƶ.

Rapid migration

Off-the-shelf carbon nanotubes were used by Bianco’s team as the basis for their ‘nano delivery vehicle’. The tubes were modified by heating them for several days in dimethylformamide, which enabled short linking chains of triethyleneglycol (TEG) to be attached. Then, a small peptide was bonded to the TEG molecule.

When the modified nanotubes were mixed with cultures of human fibroblast cells they rapidly entered and migrated towards the nucleus. At low doses the nanotubes appeared to leave the cells unharmed, but as the concentration increased cells began to die.

“The nanotubes do not appear to be highly toxic,” says Bianco. “But we do now have to work out what happens to the nanotubes in the body.”

Custom delivery

In principle, a wide range of different molecules could be attached to the nanotubes, raising the possibility of an easily customised way of ferrying molecules into cells.

This has begun to excite other researchers. Ruth Duncan, who works on drug delivery mechanisms at Cardiff University, UK, told ��è����Ƶ: “There’s a lot of evidence that other nanoparticles could be useful in delivering drugs so this is a very interesting and exciting area. But I am completely baffled about how the nanotubes manage to get into the cells.”

Duncan says researchers have tried without much success to use buckyballs – a spherical form of carbon nanotubes – as a way of ferrying anti-cancer drugs and radionucleotides into cells.

Journal Reference: Chemical Communications (DOI: 10.1039/b311254c)