Archive | March, 2008

A blast from the past

28 Mar

The following comes directly from Kanner (1965):

Questions have arisen, however, with regard to the ease with which the diagnosis was suddenly bestowed upon a relatively vast contingent of patients. Bender, who in 1942 had, as she said, “not seen very many cases in which we could make a definite diagnosis,” announced later that by 1951 “over 600” schizophrenic children had been studied in one single psychiatric unit, that of the Bellevue Hospital in New York. By 1954, she had as many as 850 cases on her list, which means an addition of about 250 in the short span of three years. It is highly improbable that all of them would be acknowledged as being schizophrenic by many other experienced child psychiatrists, and yet it cannot be denied that Bender has made careful investigations and has conscientiously adhered to her established criteria.

Out of this emerges a rather disturbing dilemma. We seem to have reached a point where a clinician, after the full study of a given child, can say honestly: He is schizophrenic because in my scheme I must call him so. Another clinician, equally honest, can say: He is not schizophrenic because according to my scheme I cannot call him so. This is not a reflection on anyone in particular. The whole concept has obviously become a matter of semantics.

It’s an interesting paper where a lot of the same ideas you’d hear today about autism are expressed about schizophrenia, a practically forgotten construct nowadays.

 

The Next Big Autism Bomb?

28 Mar

Over on the Huffington Post, David Kirby has posted about The Next Big Autism Bomb. Its a very long post so take a sammich.

The gist (with apologies to Mr Kirby) of it is that there was a conference call to discuss the autism/mito issues:

On Tuesday, March 11, a conference call was held between vaccine safety officials at the US Centers for Disease Control and Prevention, several leading experts in vaccine safety research, and executives from America’s Health Insurance Plans, (the HMO trade association) to discuss childhood mitochondrial dysfunction and its potential link to autism and vaccines.

The purpose of the call was:

“We need to find out if there is credible evidence, theoretically, to support the idea that childhood mitochondrial dysfunction might regress into autism,” one of the callers reportedly told participants.

To that end, Mr Kirby mentions four studies throughout the rest of his piece. Three are accessible but the fourth is a total mystery. This is unfortunate as it is this fourth one which the majority of his blog post relies upon for its conclusions.

The first three are discussing what the prevalence of mito _within_ autism might be. Kirby states:

CDC officials were made aware of a Portuguese study, published last October, which reported that 7.2% of children with autism had confirmed mitochondrial disorders. The authors also noted that, “a diversity of associated medical conditions was documented in 20%, with an unexpectedly high rate of mitochondrial respiratory chain disorders.”

There is a slight point of confusion to clear up here. The figure of 7.2% is from a 2005 study ‘Mitochondrial dysfunction in autism spectrum disorders: a population-based study‘.

The study (by the same author) that Kirby mentions as being published last October is ‘Epidemiology of autism spectrum disorder in Portugal: prevalence, clinical
characterization, and medical conditions‘ declares a 4.1% figure.

The reason for this is that the lead author re-examined his data from the 2005 study and adjusted it downwards in the 2007 study. So Kirby is not correct to state that the authors believe that the rate is 7.2%. The latest figure from these authors is 4.1%.

The third study that discusses prevalence is referenced by Kirby as:

They also know that some reports estimate the rate of mitochondrial dysfunction in autism to be 20% or more. And the rate among children with the regressive sub-type of autism is likely higher still.

Kirby links to a web page that is the web interface to a mail list.

Upon searching for this paper I couldn’t find it anywhere. It is not in PubMed or Google Scholar and in fact I can only find three references to it online at all.

It since transpires that this paper is not in fact a paper at all and has not been published anywhere. It is in fact a summary for attendees of a 2003 LADDERS conference in Boston, USA. Therefore it has not been subject to any kind of peer review. That’s not to say the figure is wrong, merely that it hasn’t been verified or undergone any kind of the usual scientific checks and balances a published piece of work must undertake to ensure quality.

Its also been explained to me that the percentage of “mitochondrial autism” reported by any group will vary with the percentage of regressive autism in their ASD population. So it is not true that the summary states a differential between autism and regressive autism. Rather that “mitochondrial autism” exists _within_ regressive autism.

And so we move on to the fourth study.

One doctor reported his findings from a five-year study of children with autism, who also showed clinical markers for impaired cellular energy, due to mild dysfunction of their mitochondria.

The biochemistry of 30 children was studied intensively, and in each case, the results showed the same abnormalities as those found in Hannah Poling, participants said. Each child had moderate elevations or imbalances in the exact same amino acids and liver enzymes as Hannah Poling.

All thirty children also displayed normal, healthy development until about 18-24 months of age, when they quickly regressed into clinically diagnosed autism (and not merely “features of autism”), following some type of unusual trigger, or stress, placed on their immune system.

……….

But what causes the stress? That is a very big question.

Apparently, in only two of the 30 cases, or 6%, could the regression be traced directly and temporally to immunizations, and one of them was Hannah Poling. In the other cases, there was reportedly some type of documented, fever-inducing viral infection that occurred within seven days of the onset of brain injury symptoms.

Mr Kirby makes this study the raison d’etre of the rest of his post.

I have some major concerns about this. Who is this doctor? What is this study? Where is it published? Where can we _read for ourselves_ what this study says? Without wishing to question the honesty with which Mr Kirby is posting, its obvious that – even in this post as I discuss above – errors and misinterpretations have crept in.

Lets be honest here. These are some *major* claims being made. Firstly that all 30 kids in the study regressed into clinically diagnosed autism as opposed to features of autism. All 30? That’s incredible.

Secondly that 6% of the regressions into clinically diagnosed autism are traced directly from immunisations. That’s big. That is about as big as it gets. I would really like to see this study.

I have asked (twice) in the comments section of Mr Kirby’s post to be pointed to this study. So far, no answer has been forthcoming from anybody.

However. I note that Mr Kirby states that one of the 6% is Hannah Poling. If this is so then it is not true to say that:

the…[autistic]…regression…[can]… be traced directly and temporally to immunizations

(insertions mine for clarity).

As I’ve discussed before, none of the listed symptoms attributed to immunisations can accumulate to a diagnosis of autism. So unless we can actually see this study, know who the author, see what checks and balances this paper has undergone, we’re in a bit of a limbo.

Maternal antibodies involved in aetiology of autism(s)

26 Mar

A new study released by John Hopkins indicates that maternal antibodies may play a role in the aetiology of autism:

[a]…possible explanation involves the transfer of reactive antibodies from the mother through the placenta to the fetus.

To investigate the latter, the team measured the antibody-brain reaction in blood samples from 100 mothers with and 100 mothers without a child diagnosed with autism.

Mothers of children with autism had a stronger reactivity or more areas of reactivity between antibodies and brain proteins compared with mothers without an autistic child. The presence of maternal antibodies also correlated with having a child with developmental regression, a primary feature of autism.

Things to note. No one, repeat no one is assigning _blame_ to mothers. I have no doubt there will be an attempt in some quarters to twist this into an attack on the sainthood of autism parents but its really not. Biology is biology. C’est la vie. Nobody in this study had the last name Bettlehiem.

Its a fascinating hypothesis though. Along with the latest cutting edge science that has found a genetic basis in approximately 40% of autism this hypothesis utilises good ideas in a rigorously scientific way. Of course, it may well turn out to be wildly wrong, but its a nice change to see some science that’s not about cure or vaccines but just interesting in and of itself.

Dear CDC

26 Mar

I read with interest Dr Schuchat’s opinion piece in the AJC today.

Whilst it is gratifying to see someone of Dr Schuchat’s calibre responding to previous claims regarding vaccines in autism I would like to make a few points to Dr Schuchat and the CDC in general.

Firstly, this level of response is around eight years too late. What have you been doing on the media/PR front over the last eight years? I’ll tell you what your ‘opponents’ have been doing – they’ve been conducting protests outside your offices, outside the offices of the AAP etc. They’ve been setting up and organising vaccine/autism groups and heavily marketing them via the use of organic and paid for web based advertising.

The only people who have made any kind of attempt to counter these groups and the misinformation (deliberate or not) they publish is people like myself. I am not attempting to aggrandise myself at all. I am attempting to convey to you how one sided the ‘battle’ has been over the last few years.

Where were you? You were needed. You could’ve helped. Instead you sat back and hoped this would all go away. It didn’t. It won’t.

Secondly, the level of Dr Schuchat’s response is very close to condescending. Simply stating that:

Kirby’s column included many inaccuracies related to childhood vaccines. As such, it illustrates that when it comes to immunizations, child development and specific medical conditions, the best source of guidance is the child’s health care provider.

is patronising in the extreme. The level and quality of the debate has moved on in the last eight years. Bland assurances won’t cut it. You need to be specific and offer evidence. Autistic people, parents of autistic people and interested professionals are smart enough to know and understand a certain level of science these days.

Don’t be shy about providing people with science. You have some truly excellent science on ‘your side’ as I and others have attempted to blog about in the last five years to no small effect. For example, Googling mmr autism displays, amongst others, the blog of a friend of mine – also the parent of an autistic child and also convinced of the need to blog about the bad science surrounding the various vaccine/autism hypotheses. Googling thiomersal autism brings up _this_ blog. We’re doing your job for you!

You’re being left behind in this debate. Its time you caught up.

How to create a disease

25 Mar

This piece is once again guest written by ‘Nigel’, a scientist working in the field whos real name is not actually Nigel ;o)

Followers of Andy Wakefield may not have come across a little spat which took place in the correspondence section of the journal “ Histopathology” last year. It is all to do with “ autistic enterocolitis”, the alleged inflammatory bowel disease described by Wakefield and colleagues in 1998 in the infamous Lancet paper. It is worth remembering that although the MMR-autism link garnered all the publicity, a key intermediate in the link was that measles persisted in the gut, resulted in enlarged lymphoid follicles, which then somehow caused this “ autistic enterocolitis”. At Thoughtful House in Austin, Texas, Wakefield and his acolyte Artie Krigsman, are now trying to make a buck out of treating this condition.

Professors Tom MacDonald and Paola Domizio from Barts and the London School of Medicine in London were experts for the defense in the UK MMR litigation against the vaccine manufacturers out of which Wakefield trousered one million dollars. MacDonald is a pre-eminent gut immunologist with an international reputation and was recently awarded the President’s Medal of the British Society for Gastroenterology for his scientific achievements. Domizio is an extremely well known gut pathologist and is also a senior figure in the Royal College of Pathologists in the UK.

The gist of their article (Histopathology. 2007 50:371-9) was that autistic enterocolitis does not exist. In a forensic dissection of the key paper by Wakefield and colleagues in the Am J Gastroenterology in 2000 (Am J Gastroenterol. 2000 95:2285-95), MacDonald and Domizio clearly showed that the so-called enterocolitis was due to Wakefield incorrectly deeming enlarged lymphoid follicles in the gut as pathological abnormalities, and that he had also created new and unsubstantiated pathological abnormalities to give the impression of gut pathology. The image of enterocolitis in an affected child shown in this paper was an extremely highly magnified picture of a small piece of tissue, which may in fact have come from one of the original Lancet 12 (in order to bump up the numbers of patients studied, Wakefield just reported the original Lancet 12 again). This is a familiar Wakefield tactic, his “representative” images are always taken at an extremely high magnification on the microscope, presumably to hide the fact that the rest of the tissue is normal. MacDonald and Domizio also shredded other Wakefield papers of the same ilk in their article.

Key to this piece of detective work by Domizio and MacDonald was a table in the Am J Gastro paper where these invented histological abnormalities were shown. In his response ( Histopathology 2007 50:380-4) Wakefield did not address any of the substantive points raised by MacDonald and Domizio, but stated that the pathological descriptions in the table were nothing to do with him, but were the work of Prof A Dhillon at the Royal Free Hospital in London, who was not an author of the paper. Unfortunately for Wakefield, Dhillon also wrote to the journal to say that it was nothing to do with him either (Histopathology 2007 50:794). Dhillon showed his version of the table, which unsurprisingly, because Dhillon is a bona fide pathologist, contained none of the new invented abnormalities. So we have an impasse, though not enough of an impasse to stop Wakefield publishing another paper in 2005 (Eur J Gastroenterol Hepatol 17:827-36) showing the same table again, and remarkably, reporting the Lancet 12 for at least the third time! Wakefield produced no response to MacDonald and Domizio’s suggestion that since the histopathology slides from the autistic children seen at the Royal Free Hospital in London are available, it would be a straightforward exercise to have these analysed in an anonymous and independent fashion to put this question to rest.

In response to Wakefield’s defence of his work, the editor allowed MacDonald and Domizio a final say, where they demolished Wakefield again (Histopathology 2007, 51, 552–3).

Although all of this might seem highly technical, histopathological diagnosis of gut disease is a highly skilled art, with extremely high standards, and it is scientific vandalism for non-pathologists such as Wakefield to create new and non-existant abnormalities and then use them to burden children and parents with a life-long inflammatory bowel disease. The best example of this sleight of hand is his definition that a tissue section from the gut of an autistic child was abnormal if it contained a lymphoid follicle. However when the gut biopsies were taken at colonoscopy from autistic children, lymphoid follicles were specifically targeted for sampling because they wanted to look for measles in these tissues. So it is obvious that all will have pathology if one uses this invented criteria.

Throughout this saga, Wakefield has traded on the fact that autistic children do have real gut problems. However instead of attributing these problems in the majority of children to a combination of chronic and severe constipation, fecal impaction, unusual diet, diarrhea, bloating, parasites, gas etc, he had to find a new disease! However the pediatric gastroenterologists in charge of these children at the Royal Free knew what the problem was, when they wrote in the Lancet in 1998, that following cleansing of the colon needed for colonoscopy, many children underwent rapid symptomatic improvement which was maintained if constipation was avoided ( Lancet 1998;351:908). So there you have it, an inflammatory bowel disease treatable by cleansing the colon!

An interesting post-script to all this is that when challenged with the fact that the alleged “enterocolitis” in autistic children is not different from the mild changes and ileal lymphoid hyperplasia seen in chronically constipated, developmentally normal children, Wakefield and Krigsman are now saying that the constipation in autistic children is different! Give us a break !

PS. MacDonald was also an expert witness last year in the Hazelhurst versus HHS case in the USA. In his testimony MacDonald re-iterated in some depth the extent of Wakefield’s rogue and junk science, going back all the way to his identification of measles virus in Crohn’s disease using reagents which were not specific for measles virus. However he picked up yet another deception in the Am J Gastro paper. Much of the paper deals with the alleged lymphoid hyperplasia in the ileum of autistic children, graded by Wakefield on a score 0-3, with 0 being no follicles and 3 allegedly an undefined “severe” lymphoid hyperplasia. To illustrate the colonoscopic appearances of grades 0-3, a panel of photographs purportedly showing the different grades is included as Figure 1 of the paper. The date and time each photograph was taken is reproduced in figure. The image of alleged grade 0 ileal lymphoid hyperplasia (ILH) was taken on the same day and only 1 minute 54 seconds before the image of alleged grade 3 ILH. It is impossible to remove a colonoscope from 1 child and scope another child, reaching the ileum in 1 minute 54 seconds. Therefore the grade 0 and grade 3 images were taken from the same child; the grade 0 image most probably from the caecum ( the part of the colon just after the ileum) and the grade 3 image from the terminal ileum.

Kirby continues to get basic maths wrong

23 Mar

As I’ve pointed out, Kirby has messed up his maths on the Huffington post blog. He’s now done much the same in an Atlanta Journal-Constitution article (clearly, their Editor does not check for mathematical errors, or general stupid). Kirby’s article is titled “Give us answers on vaccines”: I don’t expect any answers from Kirby, but correct sums would be a start.

Kirby argues that:

Most striking is how typical Hannah’s cellular dysfunction [mitochondrial disorder] may be among children with autism. While extremely rare in the general population, at two per 10,000 people, it seems unusually common in autism — with estimates up to 2,000 per 10,000.

To go over these figures again – a 2,000 per 10,000 incidence of mitochondrial disorder among people with ASDs is and incidence of 1/5. If 1/5 people with an ASD has mitochondrial disorder, and only 2/10,000 people have mitochondrial order, then if everyone with mitochondrial disorder has an ASD only 1/1,000 people would have an ASD. Clearly, not everyone with mitochondrial disorder has an ASD, so the actual incidence that Kirby is estimating would be considerably lower.

Age of Autism linked the blog post on Kirby’s article, and there are (at time of writing) over 170 comments. Oddly, though, it seems that no-one has picked up on Kirby’s basic error. Haven’t they noticed their hero’s issues with maths? Or don’t they care?

Statement on autism, vaccines and mitochondrial disease

22 Mar

The following was posted on the blog of the Mitochondrial Disease Action Committee yesterday.

The recent headlines concerning the potential links between autism, mitochondrial diseases, and vaccinations are evidence of the need for better understanding about mitochondrial disease. It is conservatively estimated that one in 4000 individuals are affected by mitochondrial disease, although specialists agree that the disease is under-recognized in the general population. The presentations and severity of symptoms of mitochondrial disorders clinically vary and affect both adults and children.

Vaccinations are critical in protecting the health of our children. All children, even those with suspected or known mitochondrial diseases, should receive the recommended vaccinations. The risks of these communicable illnesses outweigh the risk of vaccine-related reactions. Any causal relationship of thimerisol to incidence of autism has been disproven by observing the incidence of autism before and after eliminating this form of mercury from the vaccines. MitoAction encourages parents to talk to their pediatrician about these concerns.

David Holtzman, MD, PhD, a Pediatric Neurologist at Massachusetts General Hospital in Boston, MA, notes, “Mitochondrial Disease may present with the clinical features of Autism Spectrum Disorders (ASD). Several recent studies have documented biochemical evidence of abnormal mitochondrial functions in at least 30% of children with ASD.”

Awareness and attention to mitochondrial disorders will bring greater understanding of the impact of environmental and physiologic stressors on both autism and mitochondrial disease. Further research may explain how autism can be an expression of mitochondrial diseases and could be prevented.

Reality Bites Back

22 Mar

So many times I have heard it said by the anti-vaxx/autism believers how they are ‘the mainstream voice’ – *the* autism community.

Today, they got a bit of a reality check.

The New York Times discussed an NYT article in which parents who refuse to vaccinate their kids say:

I refuse to sacrifice my children for the greater good,” said Sybil Carlson, whose 6-year-old son goes to school with several of the children hit by the measles outbreak here………….Ms. Carlson said she understood what was at stake. “I cannot deny that my child can put someone else at risk,” she said.

This piece was written in the wake of a measles outbreak in San Diego:

In a highly unusual outbreak of measles here last month, 12 children fell ill; nine of them had not been inoculated against the virus because their parents objected, and the other three were too young to receive vaccines.

These are the same people who claim that measles is a ‘nothing’ disease – that they had it as kids and it never did them any harm. An argument that reminds me of the one elderly smokers wheel out that they smoked every day of their lives and it never did them any harm as they cough what remains of their lungs up and continue infecting the air with second hand smoke.

Lets be honest here. What these people are doing is very much akin to selfish smokers. They’re wandering up to you and effectively pissing in your face.

Here’s an article from Jan last year in New Scientist.

Deaths have fallen from 873,000 during 1999 to 345,000 by the end of 2005,” said WHO director-general Margaret Chan, on Thursday. “This is a 60% reduction.” And the news is even better in Africa, Chan said. “Deaths there declined by 75%, so Africa is leading the way.”

Measles deaths in children under five fell from 791,000 to 311,000 over the same period, globally.

The new figures estimate that, altogether, measles vaccinations have prevented 7.5 million deaths between 1999 and 2005, and 2.3 million of these were attributable to the intensified programme.

In 2005, 345,000 people *died* from measles. This is down from 873,000 people who *died* from this ‘nothing’ disease that never does anybody any harm. Are people really so purposefully stupid?

And what helped achieve this 60% drop in *deaths* – was it Jenny McCarthy doing chat shows? Was it a whole bunch of people deliberately misrepresenting what happened to a nine year old girl?

No. It was *vaccines* .

Anyway….

In the NYT thread, several stalwart commenter’s from the Age of Autism blog have turned up trying to make their points. The replies to them/before them/after them quite nicely demonstrate how isolated from the mainstream they actually are and how well informed the average person on the street has become both about the need for vaccines and about these people in particular. I do worry that they might start seeing every parent of an autistic child as an anti-vaxx loon but on the positive side, it has shown up very, very publicly how small the autism/anti-vaxx group actually is numerically as well as how little the average person believes them.

By the way, I am well aware that there is another discussion going on in another US papers comments section but I will not link to that as it contains comments about an individual that I want to distance myself from totally and will deny any knowledge of or participation in. Please do not allude to, link to or name either this individual or the newspaper in question.

Urinary opioid peptides and genes

19 Mar

Two new interesting pieces of science out this week.

Firstly was the latest piece of MMR hypothesis destroying science called ‘Absence of urinary opioid peptides in children with autism’.

MMR believers say that part of the hypothetical damage the MMR does to the gut of autistic kids is cause so-called ‘leaky gut’ syndrome, an alternative medicine hypothesis roughly suspected to be on a par with homeopathy and massaging aura’s in terms of scientific credibility.

Proponents of the autism branch of this hypothesis say that the MMR causes leaky gut and that the ‘leak’ fails to parse these urinary opioid peptides which in turn would (in effect) get the patient stoned. or to put it another way:

….these peptides result in effects which are basically opioid in nature (akin to drugs such as morphine) and that they may either, themselves, have direct opioid activity or that they may form ligands for the enzymes which would normally break down such opioid peptides that occur naturally within the Central Nervous System (CNS). In either case, the consequence would be the same. The CNS neuroregulatory role, which is normally performed by the natural opioid peptides such as the enkephalins and endorphins, would be intensified to such an extent that normal processes within the CNS would be severely disrupted…

Yeah, right.

So now some actual science (as oppose to blueskying) has looked at this. And what do they conclude:

It has been claimed for a number of years that the urine of children with autism contains exogenously derived opioid peptides. This finding is said to reflect a disturbance in the integrity of the gut epithelium, act as a diagnostic marker for autism and predict treatment response to a diet excluding gluten and casein. The aim of the present study was to determine whether exogenous or endogenous peptides were present either in the urine of children with autism, or control children.

…..

There were no significant differences between the HPLC urinary profiles of the children affected by autism and the typically developing controls. In those cases where HPLC showed peaks in the locations at which opioid peptides might be expected to be found., MALDI-TOF established that these peaks did not, in fact, represent opioid peptides at all.

……

Given the lack of evidence for any opioid peptiduria in children with autism it can neither serve as a biomedical marker for autism, nor be employed to predict or monitor response to a casein and gluten exclusion diet.

So that’s yet another nail in the undead vampire of the MMR hypothesis (in fact, is there a proper word for something which is less than a hypothesis? Even using the word ‘hypothesis’ now seems aggrandising this silliness)

On the other side of research, where actual progress is being made, an as yet unpublished study (or published but the journal issue hasn’t been released or it has and I can’t find it) has found genetic connections which they think can count towards up to 2.5% of autism:

Disruptions in the gene, called contactin 4, stop the gene from working properly and appear to stop the brain from making proper networks, the researchers reported in the Journal of Medical Genetics.

These disruptions, in which the child has either three copies of the gene or just one copy when two copies is normal, could account for up to 2.5 percent of autism cases, said Dr. Eli Hatchwell of Stony Brook University Medical Center in New York, who led the study.

Now, when we put this together with Rett, Fragile-X, Tuberous Sclerosis, de-novo mutations and a few others I can’t recall I think we’re approaching between 10 – 16% of an established genetic cause for autism(s). Slightly better than the 0% that the vaccine hypotheses are running at.

First Time a Vaccine-Autism Case Has Been Awarded… Right?

15 Mar

Wrong.

You need to go read Kathleen’s post titled A Not-So-Hidden History. For the best investigative blogging in autism, Kathleen Seidel is the go to person. Once again, it was not the “journalists” of autism (Kirby and Olmstead) who uncovered this information.

What does it mean?

Well, for one, I think that claims to the effect that the Poling case is unprecedented, an event of major significance, with pigs flying and the sky falling, have been rendered completely bogus.

Furthermore, let’s consider whether allowing such an impression to be promoted was an honest thing to do. As Kathleen notes:

In all but one of the above-listed cases with published decisions, the petitioners were represented by individuals who are now or have been members of the OAPPetitioners Steering Committee — including its chairman, Mr. Clifford Shoemaker, counsel to the Poling family.

Now, let’s think about the numbers. It appears that each year in the US about 50 vaccine injury claims are found to be “compensable” (source). What are the odds that at no point in time any of the compensated persons was autistic? We’re talking about very rare occurrences, but statistically they must occur unless autistic persons are specially immune to vaccine injury.

It’s not possible, from available data, to make an accurate determination as to whether autistic persons are more or less likely to suffer vaccine injury than non-autistic persons, and no scientific reasons to lean one way or the other.

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