Scientists have discovered the primary mechanism by which thalidomide causes malformed limbs in developing embryos.

This side-effect was recognised after thousands of affected children were born to mothers who had been prescribed the drug for morning sickness.

Research in the journal Science reveals that thalidomide binds to and renders inactive the protein cereblon, which is very important in limb formation.

This finding could help the development of safer thalidomide-like drugs.

‘Unknown mechanism’

Thalidomide can be effective in the treatment of certain cancers and leprosy, but its infamous side-effect, which is known as teratogenicity, mean that for women its use remains risky and controversial.

Medical researchers would therefore like to develop drugs that mimic the action of thalidomide, but do not affect limb development.

The research team, led by Takumi Ito from the Tokyo Institute of Technology in Japan, managed to isolate the negative effects of this "potentially useful" drug.

They set out to discover which target molecules thalidomide bound to in the body. They did this using tiny beads that extracted each individual molecule the drug bound to.

The scientists confirmed their conclusion by using genetic techniques to reduce the production of the cereblon protein in developing zebrafish and chick embryos.

The embryos with reduced cereblon had similar developmental defects to those that were treated with thalidomide.

"We [have shown] that cereblon… is a primary target of thalidomide teratogenicity," the researchers wrote in their Science article.

Dr Ito told BBC News: "Although the mechanism for the teratogenic effect was made clear, the mechanism for its therapeutic effects remains unknown.

"[If we want to develop] a new drug devoid of teratogenic activity, it is important to understand [this] mechanism… this is what we are heading for."</p

This article is from the BBC News website. © British Broadcasting Corporation, The BBC is not responsible for the content of external internet sites.

Many lives could be saved if GPs followed guidelines for reducing cholesterol in patients at high risk of heart disease, research suggests.

A study of 25,250 patients in Germany found that only about half were assigned the correct targets for lowering cholesterol.

Doctors believe the findings, published in the European Heart Journal, may apply in the rest of Europe.

Women are most at risk of being given insufficient treatment, they say.

The study found that about 50 to 80 fewer heart attacks, strokes and heart disease-related deaths per 1,000 patients could be avoided over a 10-year period if all doctors adhered to the guidelines on cholesterol-lowering targets.

Patients were more likely to be given correct targets if they had a history of heart attacks, coronary heart disease and diabetes, the researchers found.

Patient risk

Professor Heribert Schunkert, a clinical cardiologist who led the research in Lubeck, Germany, said the core question involved the perception of patient risk.

UK CHOLESTEROL TARGETS

• The government recommends that total cholesterol should be less than 5.0mmol/l
• LDL cholesterol should be less than 3.0mmol/l
• People at high risk of heart disease should have total cholesterol less than 4.0mmol/l
• People at high risk of heart disease should have LDL cholesterol less than 2.0mmol/l

"Women are often perceived as having a lower cardiovascular risk compared to their real risk, and this may lead to insufficient treatment," he said.

"This aspect has also been reported in other regions in the world."

Professor Ian Graham, head of cardiovascular medicine at Trinity College Dublin. and a spokesman for the European Society of Cardiology said the UK did better when it came to giving out correct cholesterol targets.

But he cautioned: "There is a general principle of guideline fatigue. GPs are bombarded by targets.

"It’s important to make guideline information as easy and accessible as possible."

Cholesterol is a fatty substance known as a lipid. It is carried in the blood on proteins called low-density lipoproteins (LDL).

LDL is known as bad cholesterol because it deposits cholesterol in the lining of the arteries.

The more LDL a person has, the more likely they are to develop heart disease.

Lowering cholesterol using drugs, diet and other lifestyle measures is an important preventative measure.

The government recommends that total cholesterol levels should be less than 5mmol/l.

On average, men in England have a cholesterol level of 5.5mmol/l and women have a level of 5.6mmol/l. </p

This article is from the BBC News website. © British Broadcasting Corporation, The BBC is not responsible for the content of external internet sites.

Skin transplant surgery could be an effective way of treating the skin disease vitiligo, say US researchers.

A team in Detroit transferred healthy skin cells to 32 patients who had areas of the body that had lost colour due to the condition.

They found the treated area regained on average 52% of its natural skin colour.

In some patients with a specific type of vitiligo, the treated area regained on average 74% of its natural skin colour, the researchers said.

The surgery was carried out under local anaesthetic at Henry Ford Hospital.

"Patients of colour and those with vitiligo on one side of the body and in one area of the body may benefit most from this procedure"

Iltefat Hamzavi, study author

"The results achieved in our study were of obvious significance to our patients," said Dr Iltefat Hamzavi, the study’s senior author.

Although these are just initial results, Dr Hamzavi said for some patients the surgery was more effective than standard treatments like light therapy or medication.

"Patients of colour and those with vitiligo on one side of the body and in one area of the body may benefit most from this procedure," he said.

The surgery is known as melanocyte-keratinocyte transplantation or MKTP.

Melanocyte cells, which produce pigment in the skin, hair and eyes, are taken from an area of healthy skin and separated to make a skin cell mixture.

This mixture is then applied to the treatment area and covered with a specially developed dressing.

In the study, 32 patients (18 male, 14 female) ranging in age from 18 to 60 underwent surgery.

Treated areas included hands, arms, legs, feet, face and stomach.

Maxine Whitton, patron of the Vitiligo Society, a UK charity, said the technique was unsuitable for large areas, or for actively spreading vitiligo.

"We need more studies using this technique including well-designed randomised controlled trials comparing this technique with other surgical interventions such as grafting," she said.

"The results of this study could lead to further investigation of the technique in randomised controlled trials and be useful for some people with vitiligo." </p

This article is from the BBC News website. © British Broadcasting Corporation, The BBC is not responsible for the content of external internet sites.

The doctors’ union claims that England’s medical records database is being pushed through too fast, with details sometimes being uploaded without patients’ knowledge.

But those behind the new system say many patients are astonished that hospital doctors still do not have access to basic information, and the process to opt out is very straightforward. What are the issues

What is this database

The electronic patient care records system will allow an individual’s medical records, currently held by GPs, to be accessed by NHS staff across the country.

As well as appointments, it will contain basic information about medication, allergies and adverse reactions to any drugs.

This means that doctors and paramedics will have automatic access to these details, minimising the risks posed by mix-ups and delays. At present some doctors have to wait to find out what prescription medications their patient is taking.

Further details may be added over time but the Department of Health says no sensitive information - such as HIV status for instance - would be added without a discussion between doctor and patient.

Health officials say patients will always have the right to ask a doctor to remove any details, and can review their records at any time.

How far advanced is it

To date, 1.25m records have gone onto the database, and the process is speeding up.

The plan is to have 50m records in the system by 2014.

But the doctors’ union, the British Medical Association, says this is too fast, and that some people are not aware that their records are being uploaded or do not understand how to opt out.

Why is this controversial

The major criticism is that it risks patient confidentiality.

Doctors and patient groups argue that by putting sensitive details on a national database the information could be abused and even fall into the hands of insurance companies and employers. They question the security of the system, which is part of a £12bn IT upgrade within the NHS.

The flip side is that most agree the system will improve patient care and medical mishaps, if correctly implemented.

How does a patient opt-out

Before a patient’s details go into the database, they will receive a pack containing information about the Summary Care Record. If they decide they do not want to be on the database, the pack contains an order form and pre-paid envelope which they can use to order an opt-out form.

The completed form can then be returned to the patient’s GP practice, where forms should also be available.

Alternatively, the form can be ordered by phoning the NHS Care Records service, or downloaded from the website.

The Patients Association wants all patients to be sent an opt-out form as a matter of course.

"The health service should not put in place bureaucratic obstacles to patient choice because they are worried about what patients might choose to do," says its director, Katherine Murphy.

"Many patients are rightly concerned about their confidentiality and consent and if there is even the slightest impression that this is being pushed through it will generate a feeling of mistrust. People who might otherwise have consented could end up opting out which would be the last thing everybody wants."

A spokeswoman for the Department of Health stressed however that much thought had gone into the way in which opt-out forms were provided, and that they wanted to ensure that no-one filled in the document on behalf of another. </p

This article is from the BBC News website. © British Broadcasting Corporation, The BBC is not responsible for the content of external internet sites.

Coronation Street actress Beverley Callard has revealed she has been receiving treatment for depression.

The 52-year-old actress, who plays Rovers landlady Liz McDonald, was absent from the soap for five months last year after a "serious breakdown".

She was treated at the Priory Clinic at the time and remains an outpatient at the facility.

Callard has now teamed up with mental health charity Mind to raise awareness of mental health issues.

The actress, reported to be "well on the road to recovery", said: "I feel it is really important to try and help lift the stigma that makes life so difficult for the one in four people who experience mental health problems."

‘Reach for help’

She thanked her friends, family and colleagues for their support and the media for respecting her privacy during her illness.

"Being able to recover out of the media spotlight has hugely helped me and meant that I could return to work last year whilst still receiving treatment as an outpatient.

"Now I feel able to speak about what I went through and thank everyone for their support," she said.

Paul Farmer, chief executive officer of Mind, said: "The support Bev received from her friends, family and ITV had a huge part to play in the steps she took back to good health.

"We encourage anyone who may be suffering in silence to reach out for help and urge those that they turn to, to be there for them without judgment."

A spokeswoman for Coronation Street said: "Everyone at ITV has been behind Beverley through this very difficult time.

"We are extremely proud of the huge progress she has made and delighted that she is back on screen at the centre of the show and we continue to support her."</p

This article is from the BBC News website. © British Broadcasting Corporation, The BBC is not responsible for the content of external internet sites.

Doctors’ leaders have called for a halt in the development of a medical records database for patients in England.

The British Medical Association says the computer-based Summary Care Records are being set up at "break-neck speed", sometimes without patients’ knowledge.

Ministers have expressed surprise at fears of fast change after previous criticism that it was moving slowly.

The NHS IT upgrade will link more than 30,000 GPs to nearly 300 hospitals through an online appointments system.

It will also feature a centralised medical records system for 50 million patients, e-prescriptions and faster computer network links.

But the plans have received repeated criticism over security fears and a lack of enthusiasm among doctors for the technology.

Doctors’ leaders have written to the government calling for parts of the programme to be suspended.

"If the process continues to be rushed, not only will the rights of patients be damaged, but the limited confidence of the public and the medical profession in NHS IT will be further eroded"

Hamish Meldrum
BMA Chairman

In a letter to Health Minister Mike O’Brien, the British Medical Association called for further independent evaluation of pilot schemes set up to test the system.

Summary Care Records are central to the NHS computer upgrade in England, which is the biggest healthcare IT programme in the world.

The basic record includes information on allergies, medication and adverse reactions. Further details may be added over time.

Patients are told by letter before their details go on the system, giving them the chance to opt out.

In December, the Department of Health announced that the roll-out of the records system would be accelerated.

To date, more than 1.25 million records have gone on the database and the process is speeding up. The BMA say this is happening too fast.

‘Huge concern’

It says some people are not aware that they are getting these records. It also argues that opting out should be easier.

Hamish Meldrum, chairman of the BMA, said the "break-neck speed" with which this programme is being implemented is of "huge concern".

He added: "Patients’ right to opt out is crucial, and it is extremely alarming that records are apparently being created without them being aware of it.

"If the process continues to be rushed, not only will the rights of patients be damaged, but the limited confidence of the public and the medical profession in NHS IT will be further eroded."

However, the government says the process to opt out is already straightforward.

It also argues that the BMA has supported similar schemes in Scotland and Wales.</p

This article is from the BBC News website. © British Broadcasting Corporation, The BBC is not responsible for the content of external internet sites.

VIEWPOINT
Professor Tony Leeds
Specialist in obesity management,
Central Middlesex Hospital

A big increase in obesity threatens to cause health problems for millions of people across the world.

In this week’s Scrubbing Up, obesity expert Professor Tony Leeds warns that our weight problems could also put the lives of other people at risk.

" Britain is gripped by a much-publicised epidemic of obesity - one in four of us is clinically obese.

Many obese people face an increased risk of illnesses such as heart disease, diabetes and cancer. On average, their lives will be shortened by nine years.

But some might be unwittingly putting the lives of others at risk too.

These additional fatalities are occurring not in Britain’s cardiac units, but on the country’s roads, due to people falling asleep at the wheel of cars and lorries.

But why is this - and how many of us are unwittingly potential killers

It is because Britain has yet to wake up to the dangers of obstructive sleep apnoea (OSA).

Sleep deprivation

OSA may be more common than is realised, especially in people with type 2 diabetes, where one in four might be affected.

It causes snoring, interrupted by pauses in breathing, and choking and gasping during sleep. This makes sleep disturbed and restless, and can leave people tired, irritable, forgetful and depressed. It also increases the risk that they will fall asleep at work - or while driving.

OSA can be caused by structural abnormalities of the upper airway but obesity is a big risk factor.

Extra fat next to the airway can increase pressure on the muscles which support the airway, raising the risk that it will narrow and become obstructed.

"The lifestyle of many lorry drivers means that many are significantly overweight. They lead a sedentary lifestyle, keep unsocial hours and might have unhealthy diets"

A recent British Medical Journal study showed that losing weight by following a very low calorie diet led to significant improvements in symptoms in just seven weeks for 26 out of 30 obese men with moderate or severe OSA. A longer-term US study produced similar findings.

But the risks of living with the condition were graphically illustrated by another study, which calculated that people with severe sleep apnoea were between six and 15 times more likely to be involved in a road traffic accident.

Unhealthy lifestyle

Lorry drivers seem to be particularly at risk. The typical lifestyle means many are significantly overweight - they lead a sedentary lifestyle, keep unsocial hours and might have unhealthy diets.

One study found only 11% had a "healthy" body mass index - and half were above the obesity threshold.

"Perhaps we should call for a campaign to alert all drivers to the importance of adequate sleep"

Britain’s leading sleep experts believe that nearly one in six lorry drivers could have sleep apnoea - that’s nearly 80,000.

But difficulties when driving may be under-reported - perhaps for fear of losing their licence and livelihood.

In a period of just four months, at least four cases came before UK courts of drivers of large goods vehicles accused of causing death by dangerous driving.

All four drivers were suffering from sleep apnoea - diagnosed only after these terrible accidents.

In one incident it was revealed that a lorry driver involved in a fatal crash had seen his doctor just five months before, complaining of tiredness - but sleep apnoea was not diagnosed.

BODY MASS INDEX
Calculated by dividing weight in kilograms by height in metres squared

• Normal: 18.5 - 24.9
• Overweight: 25 - 29.9
• Obese: Above 30

Calculate your BMI

At the inquest, the coroner called for a toughening of the licensing regimen for commercial drivers, including regular medical screening.

He also called for fast-track medical assessment of those involved in road traffic collisions - but stressed that a diagnosis of sleep apnoea was unlikely to force them off the roads.

Survey data and random inquiry suggest that falling asleep (even momentarily) while driving may be more common than we realise. Our lifestyles, TV and computer use nibble away at the hours of sleeping.

Perhaps we should call for a campaign to alert all drivers to the importance of adequate sleep, to the effect that being obese can have on sleep quality, and to the need for an immediate visit to the GP if sleep apnoea is suspected.

"

Have you had any of the experiences described in the article above How do you think we can make our roads safer </b

This article is from the BBC News website. © British Broadcasting Corporation, The BBC is not responsible for the content of external internet sites.

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