BBC BLOGS - Fergus's Medical Files

Archives for November 2010

Daily pill helps prevent HIV infection among gay men

Fergus Walsh | 18:44 UK time, Tuesday, 23 November 2010

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A daily pill to prevent HIV infection would be a significant development. A trial published in the New England Journal of Medicine suggests that an established treatment for HIV infection is also powerful in protecting gay men from catching the virus.

This is not, however, the answer to the nearly 30 year epidemic of HIV and AIDS. Since it is just one trial, many more studies will need to follow. But according to the Terrence Higgins Trust (THT) it is "potentially very significant and could change the HIV landscape in the future".

Some brief facts about the trial: it involved about 2,500 men at high risk of HIV infection in Peru, Ecuador, Brazil South Africa, Thailand and the United States (San Francisco and Boston). At the start of the study they had on average 18 sexual partners, which dropped to 6 by the end.

Half were given a daily pill - Truvada, a combination antiretroviral drug - which interferes with the virus's ability to replicate in cells. The other half were given a placebo - or dummy pill - each day. All were encouraged to use condoms. After a year 36 men taking Truvada had got infected with HIV compared to 64 on the dummy pills.

Many of the men failed to take the pill every day. Among those who took the medication more than 90% of the time, there were 73% fewer infections.

The treatment is known as pre-exposure prophylaxis. Dr Kevin Fenton, AIDS prevention chief at the US Centers for Disease Control and Prevention called it "a major advance". But he said it should never be seen as a first line of defence against HIV: "It's not time for gay and bisexual men to throw out their condoms".

There are many issues to resolve. The trial involved gay men and no studies have been done to show whether it would reduce heterosexual transmission. The medication was not without side-effects, including nausea. It is also expensive - costing between $5,000-$14,000 in the United States. There are also concerns that it might allow HIV-resistant strains to develop.

For the sexually active the long-standing advice to help prevent HIV infection is:

- use condoms consistently and correctly
- get tested to know HIV status and get treatment for other sexually transmitted infections
- reduce drug use and risky sex
- reduce the number of sexual partners

Given that the drug treatment is not a guarantee against infection and that it involves taking a pill every day, who might benefit?

Sir Nick Partridge, Chief Executive of THT, said it may help prevent HIV transmission among those most at risk: "We are nearly 30 years into this epidemic and yet there are still far too many people getting infected. The majority of new infections in the UK are among gay men. This might help men who seem incapable of using condoms and regularly put themselves at risk."

He also pointed out that the average annual cost of treating one person with HIV was between £7-10,000 a year, so it made good economic sense to try to prevent infection.

The news of the trial comes as figures from the United Nations show that new HIV infections and deaths from AIDS-related illnesses are declining.

Last year there were 2.6m new HIV infections worldwide - the main route of transmission being through heterosexual sex - 20% fewer than a decade ago. In 2009, 1.8m died from AIDS-related illnesses, down from 2.1m in 2004.

There are an estimated 33m people living with HIV.

There have been other encouraging developments in the field of HIV in the past 14 months. In September 2009, scientists announced that a vaccine against HIV had protected nearly one in three people from getting infected in a trial Thailand. This is clearly not a high enough success rate, but it is the best news on vaccination to emerge. In July this year research in South Africa showed that a vaginal gel containing an antretroviral nearly cut in half a women's chance of getting HIV from an infected partner.

The great genome search continues...

Fergus Walsh | 18:00 UK time, Sunday, 21 November 2010

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double helix

This is a good time to be involved in genetics. Pretty much every day it seems new genetic variations are identified which are linked to one disease or another.

Ten years after the publication of the first human genome - the entire genetic code - scientists in every field of medical research are trawling the DNA of huge numbers of patients in order to see how they vary. These genome-wide association studies provide fresh insights into disease and human development.

Two studies published in the journal Nature Genetics look at Crohn's disease and female puberty. Both are international studies involving analysis of DNA from many thousands of individuals.

The Crohn's research project was the world's largest genetic study of inflammatory bowel disease involving 22,000 patients in 15 countries. The inflammatory gastrointestinal condition affects around 1 in 500 people in the UK.

The researchers identified 39 new gene variants associated with Crohn's, bring the total to 71. The means more genes are linked to Crohn's than any other disease. Those with the condition become ill with inflammation of the gastrointestinal tract which can cause pain, weight loss, vomiting and diarrhoea - many eventually require surgery to remove part of their gut.

About half the risk of Crohn's is genetic and half environmental, possibly involving a trigger from a viral infection. The research was led by Dr Miles Parkes a gastroenterologist at Cambridge University Hospitals. He said any of the genes identified might hold the key to beating Crohn's disease - via the development of new drug treatments.

The other study found 30 genes that play a part in controlling the age at which women reach puberty. The international group of scientists, including researchers at the Medical Research Council, found that many genes responsible for sexual maturity also play a role in how a woman's body metabolises fat. The researchers suggest this establishes new biological links between going through puberty at a young age and being at increased risk of obesity.

The study involved more than 100,000 women from Europe, the US and Australia. The lead author, Cathy Elks at the MRC Epidemiology Unit in Cambridge said:

"It is interesting that several of the new genes for puberty timing have been linked in other studies to body weight gain and obesity. This suggests that women in some families may inherit a joint genetic susceptibility to weight gain and early puberty."

Many of the samples were analysed by the Wellcome Trust Sanger Institute near Cambridge, which did more of the sequencing of the Human Genome Project than any other centre.

Ten years on, this great international research effort continues to provide many new leads for scientists to follow.

Blood pressure, Barts and kidney zapping

Fergus Walsh | 18:51 UK time, Wednesday, 17 November 2010

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I wonder what the great William Harvey, physician to Barts Hospital in the 17th Century, would have made of new research there into blood pressure.

High blood pressure is often called the silent killer because it greatly increases the risk of heart disease and stroke and yet many of us don't realise we have it.

A small trial of a new technique to control blood pressure has shown promising results reported in the Lancet medical journal. Barts and the London NHS Trust was one of about two dozen centres around the world which took part.

The procedure takes about an hour and involves inserting a tube into the renal artery and zapping the nerves with radiofrequency energy. This interrupts messages from the kidney to the brain which can escalate blood pressure. In a trial of 100 patients, most of those who had the procedure had substantially lower blood pressure after six months.

The average blood pressure for the treatment group was 178/97 mmHg. Six months after treatment, it had dropped to 146/86 mmHg, a substantial fall.

What the investigators cannot explain is why 1 in 10 patients who underwent the procedure did not show any reduction in blood pressure.

Far bigger, longer trials will be needed before doctors will know whether the technique will give them a new weapon in treating hypertension.

Dr Mel Lobo, a hypertension expert at Barts believes the procedure may have the potential to save thousands of lives a year among patients who don't respond well to a range of medicines:

"We very rarely expect to see big drops in blood pressure - more than 10mm of mercury - with further changes in medication. So to be able to drop somebody's blood pressure by this much as a result of a relatively simple quick procedure is of ground-breaking importance".

After I'd finished interviewing Dr Lobo, I popped in to the museum at Barts. It's open Tuesday-Friday from 10am-4pm and is definitely worth a visit if you are interested in the history of medicine.

There's a bust of William Harvey, who was physician to Barts from 1609-1643 and who was the first person to correctly describe the circulation of the blood.

Now I'm not for one minute putting this new treatment on the same level as Harvey's breakthrough, but there's a nice sense of continuity about research into blood continuing uninterrupted for four centuries. Harvey, surely, would be fascinated.

Inquiry highly critical of pathologists for removing human tissue

Fergus Walsh | 18:31 UK time, Tuesday, 16 November 2010

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The image of pathologists and scientific researchers has taken a severe blow with the publication of the Redfern Inquiry. The 655 page report (opens pdf) details tissue samples and in some cases whole organs were removed from thousands of Britons from the 1950s until the early 1990s.

The inquiry found that relatives were seldom asked for their consent and in the majority of cases the removal and analysis of organs was "unnecessary and inappropriate".

This begs the question as to why the tissue samples were collected in the first place.

To understand this you need to think back to the post-war period and the emergence of the nuclear industry.

Although the dangers of radiation were recognised from an early stage, there was uncertainty about the long term effects on human health. Workers in the nuclear industry are screened for exposure to radiation but the effects of contamination cannot always be measured from external checks. Plutonium can lodge in organs like the lungs, liver and bone and analysis of tissue samples after death was intended to reveal any hidden dangers to health and safety from this emerging industry.

In the 1950s there was also concern that fallout from nuclear weapons tests may have exposed the public to danger, especially from strontium 90, an isotope produced only by nuclear fission. In the human body it gets concentrated in the bone. A UK wide research project collected samples of bone from more than 6000 people, mostly children who died up to 1973. The results of research showed that there was hidden threat to human health.

The Redfern inquiry found that all the pathologists who gave evidence to the inquiry had been profoundly ignorant of the law and did not realise that consent from relatives should have been sought. They believed they had carte blanche to remove tissue and organs for whatever purpose they saw fit.

This has disturbing echoes of the Alder Hey scandal. Michael Redfern QC also conducted that inquiry into the removal of body organs from 800
children at the Alder Hey Children's Hospital in Liverpool. It concluded a
pathologist "systematically stripped" organs from dead children.

The government said today that consent was now a fundamental principle and such practices would not happen today.

Painkillers, pregnancy and male reproductive problems

Fergus Walsh | 15:35 UK time, Monday, 8 November 2010

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The use of painkillers such as ibuprofen, aspirin and paracetamol during pregnancy could be linked to male reproductive disorders according to new research. A study in the journal Human Reproduction (opens pdf) found that women who took more than one painkiller at the same time during pregnancy, or who took the drugs during the second trimester, were at increased risk of giving birth to boys with undescended testicles.

The condition, known as cryptorchidism, affects about one in 20 boys in the UK. It is known to be a risk factor for male fertility problems later in life and an increased risk of testicular cancer.

1,463 pregnant women in Finland completed written questionnaires and 834 women in Denmark did the same or took part in a telephone interview. The researchers found that women significantly under-reported the use of painkillers in the written questionnaire because they did not consider mild painkillers to be "medication".

The study showed that women who used more than one painkiller simultaneously (such as paracetamol and ibuprofen) had a seven-fold increased risk of giving birth to sons with some form of undescended testes compared to women who did not take the drugs.

The second trimester appeared to be a particularly sensitive time. Any analgesic use at this point more than doubled the risk of the condition. Simultaneous use of more than one painkiller during this time appeared to increase the risk 16-fold.

The scientists behind the research believe painkillers may be part of the reason for the increase in male reproductive disorders in recent decades, possible by interfering with the role of the male hormone testosterone. Research carried out on rats in Denmark and France found that painkillers disrupted androgen production, leading to insufficient supplies of testosterone during the crucial early period of gestation when the male organs were forming. The effects of the painkillers on the rats was comparable to that caused by similar doses of known endocrine (hormone) disrupters such as phthalates - a family of chemical compounds used in the manufacture of plastics such as PVC.

Dr Henrik Leffers, senior scientist at Righospitalet in Copenhagen, who led the research, said: "If exposure to endocrine disruptors is the mechanisms behind the increasing reproductive problems among young men in the Western World, this research suggests that particular attention should be paid to the use of mild analgesics during pregnancy, as this could be a major reason for the problems".

But the study is not without limitations. The researchers could not find a statistically significant effect among the Finnish women, which was the larger group, but did find significant effects among the Danish women.

Dr Leffers said: "We do not quite understand why the Finnish cohort does not show the same associations as the Danish cohort." However, he said the telephone interviews used in Denmark gave the "most reliable information" and this may explain some of the differences. He added: "The prevalence of cryptorchidism is much lower in Finland (2.4%) compared to Denmark (9.3%) and, therefore, this would require a larger cohort to find the same number of cases."

Pregnant women in the UK are already advised to avoid taking ibuprofen or aspirin, unless they are advised to do so by their doctor.

Instead they are told they can take paracetamol. The NHS Choices website puts it like this:

Paracetamol has been used routinely through all stages of pregnancy to reduce a high temperature (fever) and relieve pain. There is no clear evidence that paracetamol has any harmful effects on the baby.

As with any medicine that is used during pregnancy, paracetamol should be taken at the lowest effective dose for the shortest possible time.

This raises a further concern with the research. Of the individual painkillers, ibuprofen and aspirin approximately quadrupled the risk of cryptorchidism. Paracetamol doubled the risk, but this was not statistically significant. This suggests that a link between paracetamol use alone in pregnancy and male fertility problems is not clear-cut.

Dr Leffers said: "Although we should be cautious about any over-extrapolation or over-statement, the use of mild analgesics constitutes by far the largest exposure to endocrine disruptors among pregnant women."

Prof Richard Sharpe of the Medical Research Council's Human Reproductive Sciences Unit at the University of Edinburgh, said:

"The studies are top quality from groups with considerable expertise. The association between painkiller (paracetamol) use in early pregnancy and increased risk of cryptorchidism in sons has been independently confirmed in another study from Denmark (MS Jensen et al. November 2010, Epidemiology). Painkillers/paracetamol are likely to be one of several factors that cause cryptorchidism - some environmental chemicals are also implicated - it is probably the sum of all such exposures that determines the outcome.

Pregnant women who are alarmed by these studies should note the following:

It is only prolonged use that has an effect - taking occasional painkiller for a headache will have no adverse effect (and the stress, worry and sickness from not taking something for a bad headache may be worse for the mother and baby).

Most women in this study who used paracetamol did not have a baby boy with cryptorchidism.

Prolonged use of painkillers in pregnancy should not be contemplated without medical approval. For certain, taking paracetamol as a 'feel good' factor should be avoided (by all of us!).

It is sound common sense to minimize your exposure (and therefore your baby's exposure) to all drugs, environmental (pesticides, paints, household chemical exposures) and lifestyle (smoking, alcohol, cosmetics usage) chemicals during pregnancy wherever possible."

Update at 17:00

Basky Thilaganathan, Spokesperson for the Royal College of Obstetricians and Gynaecologists, said:

"The findings need to be interpreted with caution. Firstly, the study shows an association rather than causation; it is entirely possible that mothers took these analgesics for an ailment (for example, a viral infection) in pregnancy that may have been the real cause for the noted problems. Secondly, the dose-dependent effect was seen in one study cohort but not another, raising the possibility that this preliminary study may be prone to inadvertent bias of patient recruitment and ascertainment. Furthermore, the definition of cryptorchidism is broad and clinical, rather than specific and the overall number of cases is so small that a small change in affected numbers would have nullified the findings.

"Given these limitations, the findings of the study should be interpreted with caution and it would be inappropriate to spread alarm to pregnant women on this basis."

Can electricity boost maths skills?

Fergus Walsh | 22:49 UK time, Thursday, 4 November 2010

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A shocking idea or a spark of genius? Scientists in Oxford say applying an electrical current across the brain may be able to enhance your mathematical abilities.

The amount of electricity is tiny - one thousandth of an amp. The electrodes are placed at the back of the head over the parietal lobe.
This is an area of the brain which is a crucial in acquiring mathematical skills. Those with dyscalculia, sometimes called maths dyslexia, often have abnormal function of the parietal lobe.

The researchers found that if the current flowed from the right of the brain to the left, then mathematical ability was enhanced. If it was reversed then it impeded learning, so that the volunteers scored no better in puzzles than a six year old.

This was a very small study with just 15 volunteers who spent many hours solving mathematical puzzles. Much bigger and more detailed research is required before any robust claims can be made about the electrical stimulation and maths ability.

Dr Roi Cohen Kadosh a cognitive neuroscientist at Oxford University kindly allowed me to take the device onto the streets of the city this lunchtime. I interviewed an entirely unscientific handful of students. I was surprised at how many were keen to give it a go, although the experiments have to be done under strictly controlled conditions in the laboratory.

One of my first questions for the scientists regarded left handedness. As a left hander I wanted to know if the current needs to flow the opposite way in order to enhance maths ability. Dr Cohen Kadosh and his postgraduate researcher are also left handed "We excluded left handers from the trial", said Dr Cohen Kadosh, "in order to get rid of a variable which could have affected the results". No doubt in future trials left handers will get their chance.

I was allowed to try out the device in the lab. I had to put on a rather natty black sports headband - the kind that John McEnroe used to wear at Wimbledon. This was purely to hold the electrodes in place. When the current was switched on I am afraid I did not feel a sudden rush of genius. In fact, I did not feel anything at all. Not a jot, not a spark, not even a mild tingling sensation. Proof, some will say, that there is nothing much between my ears.

A cure for the common cold? Excuse me while I sneeze.

Fergus Walsh | 17:55 UK time, Tuesday, 2 November 2010

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As autumn sets in, and another round of seasonal viruses infects the population, we would all appreciate a cure for the common cold. But despite interesting research from Cambridge, do not expect a breakthrough any time soon.

What scientists at the world-renowned MRC Laboratory of Molecular Biology have done is some fascinating fundamental research which appears to change our understanding of how our immune system fights viral diseases like the common cold, winter vomiting bug and gastroenteritis.

But a cure for the common cold? Excuse me while I sneeze.

Up to now it was thought that antibodies worked only outside cells, trying to destroy viruses and prevent them from infecting cells. This new research shows that, with certain viruses, antibodies cling onto them as they invade the cell.

Once inside the cell the antibodies attract the attention of a protein called TRIM21.
This in turn pulls the virus into a disposal system used by the cell to ret rid of unwanted material. This has to be done quickly, before the virus has a chance to hijack the cell to replicate itself. There's an excellent animation which shows the process.

In theory medicines might be developed which enhanced our ability to fight such viruses, but treatments would take many years to develop and test and a cure for the common cold remains a distant dream.

There are around 200 different viruses that cause the cold. In 1946 the MRC set up the Common Cold Unit on the site of a former military hospital in Wiltshire. For four decades researchers studied the effects of cold viruses on human volunteers. In 1988 the Common Cold Centre was established at Cardiff University to conduct clinical trials on new treatments for common cold and flu.

Having had a stinking cold for the past week, I will be waiting with interest to see how long it takes the researchers in Cambridge to transform their research into something of practical use to cold sufferers the world over.

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