Archive for the ‘In the news’ Category

MJA Review January 2011: Should the law on assisted dying be changed?

Wednesday, December 15th, 2010

This is a report I wrote for the Medical Journalist’s Association January 2011 newsletter.  In the above picture taken at the debate I’m the devilishly good looking chap in the front row.

The MJA discussed this contentious issue on November 25 at the Medical Society of London. Four speakers, ‘widely respected for their integrity but divided by their beliefs’, in the words of John Illman, who organised and chaired the meeting, spoke for and against modification of the law on assisted dying. Stephen Ginn reports.

Support for a change in the law came first from GP and MJA member Dr Ann McPherson. She is behind a new group called Healthcare Professionals for Change, set up to challenge the medical establishment’s stance against assisted dying for terminally ill people, and to lobby for a change in the law. Ann’s support of assisted dying is not academic; she herself is suffering from a terminal illness, a situation that, she said, made her ‘really start thinking about death’, and led her to publish an article in the BMJ explaining her views.

Ann told us that, during her working life, she had cared for many terminally ill patients, seeing many die in a way she would not wish for herself. In her view, doctors were ultimately unable to provide humane help for the terminally ill because of their inability to offer assisted dying. She wanted to see assisted dying incorporated into the palliative process. She said that she was only calling for a change in the law for specific cases: for the terminally ill who had clearly stated their wishes when of sound mind.

Baroness Ilora Finlay, professor of palliative care at Cardiff University, opposed this proposal, based on her faith in palliative care and pragmatic concerns about how assisted death decisions would be reached. For her there was a paradox inherent in the debate: increased discussion of assisted dying came at a time when palliative care was improving. She had practical doubts as to the accuracy of a terminal prognosis, the degree of internal and external coercion put upon patients, and the reliability with which patients in distress were able to make clear end-of-life decisions.
She related the case history of a patient who, with what was thought to be only days to live, had requested an assisted death in 1991, but was still alive today. She spoke of ‘societal considerations’, concluding that licensing assisted dying was not only about personal autonomy: ‘To talk about it simply as a choice is to trivialise the enormous decision we take if we change the law.’

Baroness Mary Warnock, who spoke third, is a respected moral philosopher who has expressed strong, sometimes controversial, views in favour of assisted death. She said many people wish for a good death, and some stockpiled the necessary pills, but this was ineffective because most deaths took place in hospital where medication was controlled. She was critical of doctors’ resistance to change. ‘It is simply derogatory to suggest the medical profession has the right to override the longthought- out wishes of the dying,’ she said. In her judgement, if someone wished to die, this moral decision should be taken seriously and no one else should be able to gainsay it.

She thought that the possibility some people might seek assisted death because they wished to unburden their relatives was in fact an honourable motive, to be admired. ‘Why shouldn’t I shorten my life for the sake of my children?’ she asked. Nor did she accept that a change in the law would threaten disabled people, if they made their wishes clear. ‘No one is suggesting doctors make the decision to end a life,’ she said.

Professor Mayur Lakhani, chair of the National Council for Palliative  Care, was the last to speak. In his estimation, ‘the case for a change in the law has not been made’. He reminded us that in the past 10 years little over 100 UK subjects had sought an assisted death at Dignitas, while during the same time period six million had died elsewhere. Although he felt it was important for doctors to facilitate end-of-life care, this did not imply assisting dying. In contrast to the two speakers who spoke in favour, Professor Lakhani thought it was ‘undignified to hasten death’.

The debate was opened to the floor and the audience posed questions and shared personal experiences. Someone asked about withholding medication, and Dr McPherson clarified the difference between giving medication to assist death (illegal) and withdrawing medical treatment (permitted) that resulted in death. There was general agreement that healthcare professionals found themselves as unprepared as lay people for the death of a loved one. Although there was no concluding vote, my impression was that most present were in favour of a change in the law. Debate continued over dinner, some saying that their opinion had been changed by the arguments they had heard.

Chilean miners to get antidepressants

Thursday, August 26th, 2010

There are 33 miners who are trapped deep underground in Chile.  Although lucky, in that they are still alive, by the standards of mining accidents they now face a four underground month wait until they can be brought to the surface.

Media and public interest has been running high and concern has been inevitably been raised about the psychological effect of the prolonged incarceration on the miners. 

The Chilean health minister addressed this:

"We expect that after the initial euphoria of being found, we will likely see a period of depression and anguish," he told reporters. "We are preparing medication for them. It would be naive to think they can keep their spirits up like this."

As a result alongside food and clothing, the Guardian reports that antidepressants are being provided to the miners. 

What, I wonder, is an appropriate mental state for a trapped miner?  So far the reports from underground suggest that the miners are actually coping pretty well.  They siphoned water from the radiators of their vehicles, they rationed their food.  These men are seasoned miners in a dangerous job but yet it is fragility rather than resilience that is assumed for them. 

It may be that antidepressants may eventually be reasonably offered in some cases, but blanket prophylaxis is surely not necessary. 

Mephedrone

Sunday, April 4th, 2010

mephedrone-crystal

Last week the British Government made clear its intention to ban the currently legal stimulant 2-methylamino-1-p-tolylpropan-1-one also known as mephedrone.

For anyone who lives in a cave, mephedone is a chemical that has stimulant properties when ingested and has recently become very popular on the club scene as a ‘legal high’.  It’s from the cathinone class of compounds.  This class also includes the active ingredient in khat, a plant whose leaves are chewed with great enthusiasm in Yemen.  It’s not difficult to see why mephedrone has purportedly become so popular (no figures actually exist).  It’s been legal up until now so has been extremely easy to acquire without consorting with grubby drug dealers.  Further it’s cheap and the quality of supply is reasonably reliable, unlike illegal equivalents.

Some things about the mephedrone story are quite novel.  Legal highs, which once had a reputation for poor efficacy are now causing a great deal of interest.  The internet is making the drug much more easily available than it would have been under similar circumstances twenty years ago.  The emergence of China’s economy has meant that there is plenty of capacity for manufacture.

What’s less new is this reminder of quite how much we British like getting off our heads.  The stereotyped response from the media and UK Government also comes as no surprise.  The media have focussed their attention on a number of deaths with which mephedrone has been associated, although no causal link has established.  The Government’s actions in banning the drug appear dictated by tabloid furore and based on moral panic and a wish to seem decisive with an election six weeks away.

The use of psychoactive substances of unknown toxicity being used recreationally is a legitimate focus for government concern.  However the advice to ban this drug was provided by an advisory council (The Advisory Council for the Misuse of Drugs) on which three places remain unfilled and prohibition under these circumstances may not be legal.  The ACMD’s report on mephedrone has not been made available for public scrutiny.

The ACMD’s enfeeblement may matter little to the Home Secretary. He appears not to listen to his advisors anyway.  Another AMCD member yesterday over the affair.  He wrote in his resignation letter:

“We had little or no discussion about how our recommendation to classify this drug would be likely to impact on young people’s behaviour. Our decision was unduly based on media and political pressure”

Unfortunately evidence based drugs policy does not exist in this country.  If it did any deliberation of this new drug would surely have been more considered and we’d be able to admit that mephedrone is a side show compared to the damage done to health by alcohol and cigarettes.  It is also inconsistent to ban mephedrone and not khat, which was omitted from the ban presumably to avoid pissing off ethnic minorities.

It’s true that based on its chemical class mephedrone use is unlikely to be without hazard.  However banning it will throw up another set of issues from fatalities owing to adulterated supply to deadly turf wars.  Moderate voices, including the former head of the ACMD, suggest that the most appropriate way of dealing with drugs of unknown toxicity is a ‘class D’ whereby a drug is “quarantined” and sale of it to anyone under 18 is prohibited.  Thereby allowing time for a thorough examination of harms.

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Further reading:

Drugscope article: Mephedrone – the future of drug dealing?

Druglink blog: Media muddle over mephedrone

Smart Drugs

Wednesday, March 17th, 2010

super-smart-drugs

In a debate that’s only going to get more interesting, there were recently calls for universities to consider dope testing to detect the use of ‘smart drugs’ amongst their students.  These drugs, also known as nootropics (an inelegant name; from the Greek roots noo-, mind and -tropo, turn, change) or cognitive enhancers are becoming increasingly widely used.   If the high estimates of use are to be believed then the debate about and reporting of their use has been remarkably restrained, especially when compared to the perpetual state of conflict over cannabis classification and the coverage given to mephedrone.

Cognition enhancement by pharmaceutical means is not actually a new phenomenon; caffeine is in fact a cognitive enhancer with which we are all already well acquainted.   Modern cognitive enhancers were not originally developed with the intention of improving concentration in healthy people.  Methyphenidate (also known as Ritalin) was originally licensed for attention deficit hyperactivity disorder and modafinil for narcolepsy.  Other drugs such as donepezil are licenced for use with people suffering from dementia.  Most of the drugs effect the chemical pathways of neurotransmitters dopamine and noradrenaline in the brain.

The main effects of cognitive enhancement drugs are said to be to improved cognition, memory, intelligence, motivation, attention, and concentration.  Research has found that they improve the performance of healthy people on tests of cognitive function. They are easy to purchase over the internet and appear to display minimal adverse effects.  Most people agree that there are large groups of people for whom prescription of cognitive enhancement medication is extremely appropriate, such as those suffering from neuropsychiatric disorders.  It is their use in the healthy which is likely to become increasingly controversial.

There are of course plenty of drugs that healthy people like to take, but most of the others have been made illegal.  This prohibition been justified on basis of harm to the individual and society, but fear of the consequences of unrestricted hedonism of the proles also plays its part.  This latter issue may tell us why drugs that encourage studious academic application are not causing much of a stir.  Complacency may be misplaced as methylphenidate is a stimulant and does have addictive potential; anyone who works more efficiently has additional time for carousing.

Cognitive enhancers would seem unsuitable to join the ranks of banned substances and are likely to be here to stay.  The current economic situation may necessitate many of us to work into our 70s, and cognitive enhancement may allow older employees to remain more competitive.  They have already thought to have been used to improve the performance of soldiers in Iraq, and the UK Ministry of defence may have acquired a supply.  Baby-Boomer dementia may lead to high demand and pharmaceutical companies are unlikely to forsake a major market for their products.  The appetite for regulation does not appear to be particularly strong.  The Advisory Council for the Misuse of Drugs’s 2008-2009 report (pgs 2 and 32) only mentions that the UK Government has “asked for advice”.

Some people see no problem with using pharmaceuticals to improve on our abilities, whilst others feel that to use substances to gain advantage is unfair.  Anyone who seeks to restrict cognitive enhancement drugs on this basis must answer the charge that unfair advantage is already ubiquitous and generally tolerated in our education system.  Cognitive enhancers could in fact actually correct rather than exacerbate educational inequality.  The argument that students will feel obliged to take cognitive enhancers should all their colleagues be doing so is a stronger one, but restricting the autonomy of all people for fear that it may influence the actions of some is philosophically fraught.  Drug testing students before exams is unlikely to be practical, especially since advantage could be gained by students using cognitive enhancers using revision periods.

Maybe the most pressing concern is that many users are buying their medication off the internet.  This is unregulated and possible drug interactions and side effects go unsupervised.    There are also concerns about the effects of long term use of cognitive enhancers and also of their effects in the young on the developing brain.  One option to introduce some supervision and expert advice would be for medical professionals to more routinely prescribe these medications, although this is unlikely to be something that publically funded health services could underwrite .  Many doctors may feel uneasy about administering medication to the healthy, but it may not be long before we begin to recognise and treat “poor concentration”.

See also:

Cakic V. Smart drugs for cognitive enhancement: ethical and pragmatic considerations in the era of cosmetic neurology. J Med Ethics 2009;35:611–615

Smart drugs: lecture to the Royal Institution of Great Britain Prof Barbara Sahakian 22 February 2010

Turbocharging the Brain–Pills to Make You Smarter? Scientific American October 2009

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Energy use in Hospitals

Thursday, January 7th, 2010

SwitchItOff

Here’s a short piece I wrote for BMJ.com blogs:

According to a recent article in the Guardian newspaper I’ve worked in the two most polluting buildings in the UK. Over the course of one year the Royal London Hospital in Whitechapel was responsible for the emission of 46,218 tonnes of CO2, (rated G). Cambridge’s Addenbrooke’s hospital – in whose A&E department I worked – was the second worst, receiving an F rating. Overall eight of the ten worst polluting buildings in the UK were hospitals which on average emitted 4089 tonnes of CO2 per institution yearly. At the other end of the scale, tourist information centres emit on average 140 tonnes per year.

Hospitals are always going to struggle to be energy efficient. Despite modernisation many are still sprawling behemoths with “legacy” buildings whose origins sometimes stretch over the course of more than a century. In those days ‘energy efficiency’ was having a rest before beating the maid. Unlike offices, the nature of health care means that hospitals never close and heating costs will be high due to the needs of ill patients.

But still, walk into any hospital department and you’ll find every room is lit at all hours and every computer terminal is on whether or not it is being used. Heating systems are unresponsive and temperature regulation tends to involve opening the windows. This profligacy is hardly surprising as there’s little incentive to conserve* and things like computers aren’t designed to be powered down anyway. Some lights have most likely not been turned off for several years and I’ve only every worked in one place with motion activated lights.

All this will change I hope, although compared with, say, hand disinfecting energy efficiency has a very low profile in the NHS.

* NB: Lest it be thought I am preaching, I am no better than anyone else in this regard.

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Links

BMJ and the Hippocratic Oath: how the BMJ fails on both

NHS sustainable development unit – they’re not completely ignoring the problem it seems

Maisy and George and the future of their planet – a rather mawkish film by the BMJ, but some interesting interviews

NHS needs to tackle energy consumption – Telegraph 22 June 2007

“A muddled moral and political agenda”

Sunday, November 1st, 2009

drugs_graph_416

Having been sacked from his position as the chief UK government drugs advisor Professor David Nutt may today be reflecting on the precarious position of anyone who seeks to advise politicians on controversial matters.

For it seems that whilst such an advisory position would appear to call for candour as a job requirement, in reality an expert who expresses an opinion out of step with the thinking of his or her political masters will find this leads to chastisement and the possibility of dismissal.  Nutt irked Home Secretary Alan Johnson by penning an article which criticized the UK’s drug classification system and in particular the way in which the previous Home Secretary Jacqui Smith ignored learned advice against reclassifying cannabis from class C to B.  He also suggested that if the argument against the use of drugs by UK subjects is driven by the drug’s perceived harms, then it would be appropriate to compare these harms to the risks run by users of currently legal drugs as well as other harmful activities.

As far as the Alan Johnson is concerned, this is so say the unsayable.  In his letter requesting Professor Nutt’s resignation Johnson wrote “It is important that I can be confident that advice I receive from the AMCD (Advisory Council for the Misuse of Drugs) will be about matters of evidence.  Your recent comments have gone beyond such evidence and have been lobbying for a change in government policy”.

When it comes to drugs, Mr Johnson is not the only person who has admired scientific advice only insofar as it agrees with current policy.  As well as ignoring the AMCD’s advice regarding cannabis, Jacqui Smith also vetoed their recommendation that ecstasy be downgraded from a class A drug, a conclusion that involved the AMCD  reviewing four thousand scientific papers over a twelve months period.  Internationally the situation is hardly better.  In 1995 the World Health Organisation conducted a thorough survey on global cocaine use.  Although eventually leaked, the full report was never officially published as the US representative to the WHO threatened to withdraw funding unless the organisation dissociated itself from the conclusions of the study and cancelled its publication.  The report had suggested that use of cocaine did not necessarily lead inexorably toward either individual or societal collapse.

The debate on drug legalization appears, as Professor Nutt has found, to be almost uniquely charged.  The reasons for this are complex but perhaps are rooted in drug use’s consequences being, at worst, easy fodder for any right wing commentator: people enjoying themselves, youth running amok and slothful hippies; successive governments have run scared from sections of the popular press that purport to represent the attitudes of the public.  It is reasonable to be very wary of drugs as some, but not all, of them have the potential to do great harm but our current debate is distorted and muddled and the focus on illegal drugs in isolation blinds to the damage currently visited by the excess use of alcohol.

Despite the positioning of politicians, Dr Nutt’s resignation shows us that UK drug policy is clearly driven not by sober reflection of evidence and what this tells us about harm, but rather lip service is shown to scientific opinion which then partially conceals an unacknowledged moral and political agenda.

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Latest news

Ministers face rebellion over drug Tsar’s sacking Guardian 1 November 2009

Drugs: Prejudice and political weakness have rejected scientific facts Observer 1 November 2009

Today programme interview with David Nutt 31 October 2009

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This post is also published on Forth :: forward thinking from Ireland

Nutt decision shows the immaturity of the marijuana debate

David Nutt resigns

Friday, October 30th, 2009

nutt

Chief government drug advisor Professor David Nutt, has resigned from his position today following an publication in which he discussed the relative harms of currently illegal substances compared to those which are widely available such as alcohol.  Seems sensible, but the distinctly illiberal Alan Johnson MP seems unprepared to enter into nuanced debate.

This is not the first time Professor Nutt has landed himself  in trouble with a Home Secretary;  he was severely reprimanded by Jacqui Smith in March 2009 following publishing an article which compared the dangers of using ecstasy with those of horse riding.  But clearly he’s now used up all his nine lives.

Paper trail:

The publication in question:
Estimating drug harms: A risky business

Digest in Guardian 29 October 2009
The cannabis conundrum

Guardian 30 October 2009
Government drug advisor David Nutt sacked

The Sun 29 October 2009
Drug advisor on wacky baccy?

The Guardian 30 October 2009 Robin Murray
A clear danger from cannabis

Guardian 30 October 2009
Chief drug advisor David Nutt sacked over cannabis stance

Guardian 31 October 2009
Drugs policy: shooting up the messenger – Editorial

Guardian 31 October 2009
Professor Nutt’s sacking shows how toxic the drugs debate has become

BBC Mark Easton Blog
Nutt gets the sack – includes Alan Johnson’s letter and David Nutt’s reply

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‘Sexting’

Saturday, August 8th, 2009

There’s a new moral panic this week.  Teenagers are ‘sexting’ each other and, using magic new distribution channels, sometimes these images are distributed way beyond their original recipients.   There’s concern that once set free, sexts are being seen by paedophiles.  As the Mirror newspaper puts it Sex texts sent by teens found on pervert websites.

Paedophiles again eh? They’re everywhere! The Reds have long since ceased to be found under our beds, and this group now cosy up with the equally disparaged – and by and large mythical – terrorists.  They’re all so busy that I doubt they get to meet much.  In reality I expect that paedophiles supposed connection with sexting is tenuous at best as unfortunately they have no need to content themselves with grainy mobile phone videos and they have been inserted into this story to obscure unacknowledged disapproval of teenage sexual relations and to bolster the sense of outrage.

Not that it’s not worth pointing out the dangers of engaging in this sort of thing.  I’m sure that some teenagers have found themselves severely embarrassed when compromising pictures of themselves have been widely aired, and we all remember what happened to Tommy in Trainspotting.  But I find it hard to suppress my feeling that for these unfortunate few, and painful as it is, this could well be the sort of life lesson that we all have to learn from time to time about considering the possible future consequences of one’s actions and sexting will be as passing a concern as happy-slapping was a few years ago.

But to leave the discussion here is to miss the greater issue.  This week there’s an advertisement all over London for Chelsea Handler’s E! show in which someone with a baseball hat is looking up her skirt.  Last year there was a popular film called Zac and Miri make a porno. In my local gym they offer pole-dancing classes, and in every newsagent there are countless soft porn mid-shelf magazines.  Inevitably all this raunch has been marketed to us as a way for women to empower themselves but it’s not clear exactly where empowerment ends and good ol’ sexual exploitation begins.  A market driven society which views people as consumers and uses visions of sexual availability to sell products has led the young to view themselves as equally consumable.  When one of the most prominent models for femininity is the sex kitten, is it surprising that lustful teenage boys, now see nothing wrong about requesting revealing pictures of women of their acquaintance, or that their female peers, who do not yet have the sense that adulthood brings, feel compelled to comply.

BBC: Police warn of teenage sexting
Guardian: Don’t you know what sexting is?

“I don’t think what I’m doing is anything different to what Britney does in her new video. Plus, I love the attention” – Nancy, 14

Comment is free Guardian: Why I welcome the decline of the Twittering classes

Assisted suicide, Dignitas, Sir Edward Downes

Wednesday, July 15th, 2009

I wrote a post about rational suicide a few weeks ago which attracted a lot of interest, and even spawned a post on another site dedicated to debunking my viewpoint.  This issue and that of physician assisted suicide is rarely far from the headlines and clearly is a subject which excites strongly held opinions.  Most recently conductor Sir Edward Downes and his wife are reported to have died together at the controversial Swiss assisted suicide clinic Dignitas.  For a small organisation it attracts an impressive amount of coverage and its actions may have a substantial influence on future UK legislation.

For many people the discussion of the right to die is a simple one: people should not have to suffer toward the end of their lives and have the right to choose the time and means of their own passing.  This attitude is in line with the increasing emphasis on choice and self determination in our society of which suicide is perhaps the ultimate expression.  There are strong emotions involved and polarized viewpoints, but shouldn’t mean that we shy away from discussion both about philosophical underpinnings as well as more practical aspects.

I am concerned that where assisted dying to become legal in this country doctors would be expected to take a central role and this would sit unhappily with our usual duties.  Psychiatrists would regularly be called up to make difficult assessments about capacity and some of us might find being asked to assist in someone’s death very distressing.  Outside these professional concerns, and more fundamentally, is the message that legalised assisted dying would send out to vulnerable people who are near to the end of their lives.  Elderly people may worry that they are a burden or that their care is costing too much, and with a legal way of reaching a swift resolution may feel a duty to move on.  I cannot see how we could safe guard against this.

Sir Edward was elderly and frail but not terminally ill when he chose to take his life.  Apparently decided that he could not live without his wife and choose to end his life when she was choosing to end hers.  Most discussion about assisted suicide has focused on incurable conditions, which Sir Edward did not have.  Enabling people in similar situations to Sir Edward to take their own lives is disquieting to me.

Addendum 16 July 2009
What I think about Sir Edward Downes’ decision to ‘die with dignity’ Guardian

In the news – update

Tuesday, May 12th, 2009

coloured drugs

On April 7 2009 I posted about a report by the BBC

The Today Programme reported today that care home children whose behaviour during the 1970s/80s was controlled using large doses  of medication have subsequently given birth to children with birth defects.   The drugs in question included Haloperidol, Droleptan and Depixol.  The BBC have Professor Jeffrey Aronson, professor of clinical pharmacology at Oxford University who says that high doses of such drugs can cause genetic damage.  Presumably he’s suggesting that the drugs cause damage to unfertilized eggs – rather than being teratogenic.  These drugs can currently be given to women of child bearing age.  It’s obviously concerning that large doses of sedatives should be given to anyone without a mental health disorder (or even with…) but if they’re right (nb: it doesn’t sound like a very rigerous report and there could be other causes for what they’re suggesting has happened) this would have wide ranging implications.

I contacted Professor Aronson and he was kind enough to reply

At the moment a possible association between psychotropic drug administration and later birth defects (transgenerational transmission of an epigenetic defect) is hypothetical but worthy of further study.

Transgenerational epigenetic effects have been demonstrated in animals and there is some evidence that they may occur in humans. Diethylstilbestrol was used from the 1940s to the 1970s to prevent spontaneous miscarriages. It was subsequently discovered that the daughters of women who had been given it developed vaginal adenocarcinomas. That was a direct teratogenic effect, albeit an unusual one because of the time it took after birth to occur. However, there is now evidence of a transgenerational epigenetic effect as well–the children of those daughters have abnormalities that include hypospadias in boys [1], menstrual irregularities and possibly infertility in girls [2], esophageal atresia/tracheoesophageal fistulae [3], and possibly ovarian cancers [4]. The data are not conclusive, but they are suggestive. Children of those who were affected by thalidomide may also have an increased incidence of limb deformities [5].

This means that theoretically a genotoxic effect could cause epigenetic birth defects down the line, even though the child was not exposed in utero. Cytogenetic abnormalities have been shown in the blood cells of patients exposed to antipsychotic drugs and benzodiazepines for more than 1 month [6]. I know of no evidence about oocytes.

This combination of observations, taken with the story that has just been reported, suggests that the possibility of a transgenerational epigenetic effect of psychotropic drugs should be investigated. It does not, however, prove the association that has been reported, which is based on circumstantial anecdotal evidence and could be subject to confounding by other factors that the affected women shared. 

1. Brouwers et al. Hypospadias: a transgenerational effect of diethylstilbestrol? Hum Reprod 2006;21(3):666-9.
2. Titus-Ernstoff et al. Menstrual and reproductive characteristics of women whose mothers were exposed in utero to diethylstilbestrol (DES). Int J Epidemiol 2006;35(4):862-8.
3. Felix et al. Esophageal atresia and tracheoesophageal fistula in children of women exposed to diethylstilbestrol in utero. Am J Obstet Gynecol 2007; 197(1): 38.e1-5.
4. Titus-Ernstoff et al. Offspring of women exposed in utero to diethylstilbestrol (DES): a preliminary report of benign and malignant pathology in the third generation. Epidemiology 2008;19(2):251-7. 5. Holliday R. The possibility of epigenetic transmission of defects induced by teratogens. Mutat Res 1998; 422(2): 203-5.
6. Bigatti et al. Increased sister chromatid exchange and chromosomal aberration frequencies in psychiatric patients receiving psychopharmacological therapy. Mutat Res 1998;413(2):169-75.