Microglial Activation and Increased Microglial Density Observed in the Dorsolateral Prefrontal Cortex in Autism.

4 Aug

Here is a study that will likely be discussed for a long time to come. There has been a lot of interest in the study by John’s Hopkins researchers (Pardo, et al.) on microglial activity in the brains of autopsied autistics. A paper just released by Prof. Pardo together with Prof. Courchesne at UCSD shows markedly increased microglial cell activiation in 5 of 13 autistics, including children under 6.

The exact implications of this are not yet determined. The authors conclude the abstract with

“Given its early presence, microglial activation may play a central role in the pathogenesis of autism in a substantial proportion of patients. Alternatively, activation may represent a response of the innate neuroimmune system to synaptic, neuronal, or neuronal network disturbances, or reflect genetic and/or environmental abnormalities impacting multiple cellular populations.”

Here is the full abstract:

Biol Psychiatry. 2010 Aug 15;68(4):368-376.
Microglial Activation and Increased Microglial Density Observed in the Dorsolateral Prefrontal Cortex in Autism.

Morgan JT, Chana G, Pardo CA, Achim C, Semendeferi K, Buckwalter J, Courchesne E, Everall IP.

Department of Neuroscience, School of Medicine, University of California, San Diego, La Jolla, California.
Abstract

BACKGROUND: In the neurodevelopmental disorder autism, several neuroimmune abnormalities have been reported. However, it is unknown whether microglial somal volume or density are altered in the cortex and whether any alteration is associated with age or other potential covariates. METHODS: Microglia in sections from the dorsolateral prefrontal cortex of nonmacrencephalic male cases with autism (n = 13) and control cases (n = 9) were visualized via ionized calcium binding adapter molecule 1 immunohistochemistry. In addition to a neuropathological assessment, microglial cell density was stereologically estimated via optical fractionator and average somal volume was quantified via isotropic nucleator. RESULTS: Microglia appeared markedly activated in 5 of 13 cases with autism, including 2 of 3 under age 6, and marginally activated in an additional 4 of 13 cases. Morphological alterations included somal enlargement, process retraction and thickening, and extension of filopodia from processes. Average microglial somal volume was significantly increased in white matter (p = .013), with a trend in gray matter (p = .098). Microglial cell density was increased in gray matter (p = .002). Seizure history did not influence any activation measure. CONCLUSIONS: The activation profile described represents a neuropathological alteration in a sizeable fraction of cases with autism. Given its early presence, microglial activation may play a central role in the pathogenesis of autism in a substantial proportion of patients. Alternatively, activation may represent a response of the innate neuroimmune system to synaptic, neuronal, or neuronal network disturbances, or reflect genetic and/or environmental abnormalities impacting multiple cellular populations. Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

PMID: 20674603 [PubMed – as supplied by publisher]

Diagnosis of autism occurs much later than it should among Medicaid-enrolled children

4 Aug

This from a recent study by Prof. David Mandell’s group. The abstract is below:

Psychiatr Serv. 2010 Aug;61(8):822-9.
Age of diagnosis among medicaid-enrolled children with autism, 2001-2004.

Mandell DS, Morales KH, Xie M, Lawer LJ, Stahmer AC, Marcus SC.
Abstract

OBJECTIVE: This study examined child- and county-level factors associated with age of diagnosis of autism among Medicaid-enrolled children and the change in age of diagnosis over time. METHODS: National Medicaid claims from 2002 to 2004 were used to identify age of diagnosis and characteristics of children younger than ten years old with a diagnosis of autism (ICD-9 codes 299, 299.0x, or 299.8x). These data were linked to county-level education and health care variables. Linear regression with random effects for state and county was used to examine associations between these variables and age of diagnosis. RESULTS: A total of 28,722 Medicaid-enrolled children newly diagnosed with an autism spectrum disorder were identified. Their average age of diagnosis was 64.9 months. Adjusted average age of diagnosis dropped 5.0 months for autistic disorder and 1.8 months for other spectrum disorders during the study period. Asian children were diagnosed earlier than children in other racial or ethnic groups, although these differences were much more pronounced for other spectrum disorders than for autistic disorder. Children eligible for Medicaid through the poverty category were diagnosed earlier, on average, than children who were eligible through disability, foster care, or other reasons, although this difference decreased over time. Children in large urban or rural counties were diagnosed later than children in small urban or suburban counties. CONCLUSIONS: Findings showed that diagnosis of autism occurs much later than it should among Medicaid-enrolled children, although timeliness is improving over time. Analyses suggest that most of the observed variation is accounted for by child-level variables, rather than county-level resources or state policies.

PMID: 20675842 [PubMed – in process]

The age of diagnosis in California for the general population was 3 years by 2000 (falling from 6 in 1992) according to a recent paper by Bearman’s group at Columbia. Why are medicaid children diagnosed later?

I find it odd that children on medicaid due to poverty are diagnosed earlier than children “eligible through disability, foster care, or other reasons”. Naively, I would expect the opposite: that children already identified with a disability would be under greater scrutiny and more likely to receive evaluations to determine an ASD diagnosis.

Much more can be said about this, but I will stop with “Diagnosis of autism occurs much later than it should among Medicaid-enrolled children”. This is just wrong. We as a society should take better care of our most vulnerable.

The California pertussis outbreak of 2010

4 Aug

If you haven’t already heard, California is in the midst of a major outbreak of pertussis (whooping cough). The California Department of Public Health is predicting that this could be the biggest outbreak in 50 years.

Here is a graph from the CDC (via the LA Times) which shows the number of pertussis cases in the entire US as a function of time up to and including the 2004/5 outbreak:

That was not just the sort of cyclic bump seen every 4-5 years even with vaccines. That was a big outbreak. And, now, California is set to see an even bigger outbreak.

So far 7 infants have died. They were too young to be vaccinated. What is especially troublesome is that usually the worst part of the year starts in August. Here is a figure from the CDPH comparing this year to last year:

By this time last year, no children had died.

Why bring this up on an autism blog? Because unfortunately much discussion focuses on vaccines and pertussis is a vaccine-preventable disease. Many autism organizations promote under vaccination or skipping vaccination. Also, groups such as the self-named “National Vaccine Information Center” (NVIC) use autism as a major part of their message touting the dangers of vaccination. Because of this, these groups react strongly to accusations that these outbreaks are due to their activism. Such an accusation came from Nancy Snyderman of MSNBC

http://www.msnbc.msn.com/id/32545640

Visit msnbc.com for breaking news, world news, and news about the economy

Dr. Snyderman is an “unabashed advocate” for vaccines and points out that people who selectively undervaccinate put people like the immune compromised and the very young at risk.

As you might imagine, these strong comments brought a strong response. Becky Estepp of Talk About Curing Autism gave her response at the at the Age of Autism blog.

Barbara Loe Fisher of NVIC defended her group’s positions even before the MSNBC spot aired:

After watching the NVIC video I had a lot of questions. I posed a few of them to the California Department of Public Health. I appreciate them taking the time to reply:

NVIC states that there are outbreaks every 4-5 years and that “this is nothing new”. I asked CDPH:

There is an outbreak every 4 to 5 years (implying this is no big deal). I think this is correct as far as it goes, but the magnitude of this outbreak appears to be large. Is there public data on the size of previous outbreaks to compare this one to? I realize that will likely involve an estimate of the size of this year’s outbreak.

Yes, historically, there are “peak years” for pertussis every 3-5 years. This was true for other vaccine preventable diseases as well before they were controlled by vaccination. This is because once a disease sweeps through a population it takes at least a few years for adequate numbers of susceptible people to accumulate again in the population to allow sustained, widespread transmission of the disease. What is different about pertussis than other vaccine-preventable diseases such as measles, is that, unlike measles, neither pertussis vaccine or disease confers lifelong immunity. Pertussis susceptible people accumulate in the population via birth cohorts who are too young to be vaccinated, people whose immunity from vaccine or disease has waned, and people who are eligible to be vaccinated, but are unvaccinated.

The last peak year for pertussis in the U.S., including California was in 2005. This was a nationwide peak year with over 25,000 cases in the U.S, the most cases in 45 years, and over 3,000 cases in California, including 8 deaths. Although Tdap was first licensed in June 2005, not many people received it that year and it did not have an effect on the outbreak. We now have Tdap to use as a control measure that was not available in other peak years. Therefore, we are trying to increase the level of pertussis immunity in the population by encouraging the use of Tdap, particularly in people who have contact with infants.

California is having a peak year/epidemic in 2010. If current trends persist, there will be more cases in California this year than in 2005 and more cases than in 52 years (see attached document, which has been released to the public). Although some other states are reporting increases this year, no state has reported an increase similar to that seen in California, which has now had a six-fold increase from the numbers reported during the same time period in 2009, a non-peak year.

NVIC seems to be implying that parapertussis is the cause of the outbreak and that is not covered by the vaccine. Aren’t many cases, especially those hospitalized or the deaths, confirmed by PCR?

Parapertussis is also circulating and pertussis vaccine does not provide protection against parapertussis. However, we do not think parapertussis is the cause of our epidemic because most of the reported pertussis cases in California are laboratory confirmed to be pertussis. In addition, parapertussis does not kill healthy young infants. Tragically, there have been seven infant deaths in Calfornia this year, all of whom had laboratory confirmed pertussis.

NVIC is also claiming that B. Pertussis may be mutating away from the vaccine strain, so the vaccine would be failing. Besides being at odds with her own assertion that the outbreak is due to parapertussis, is there evidence for this? Are the outbreaks in unvaccinated individuals? The comparison is, of course, most valid in the very young, where immunity will not have had the chance to wane.

We are not aware of any evidence that the currently circuclating strains of pertussis are not covered by the vaccine. Of the reported cases for whom we have vaccination information, most were unvaccinated or undervaccinated. None of the seven infants ❤ months of age who died had received any pertussis-containing vaccines.

I have a lot more questions and there is much to deconstruct in the NVIC and TACA statements, but this is not the time for that.

Is the current outbreak due to the activities of groups like NVIC, TACA and the Age of Autism? Let me put it another way since accusations bring on such strong reactions from these groups: does it matter right now if they are at fault? People are dying. The goal right now is to minimize suffering and death. Vaccines do offer protection and could limit this outbreak.

Another example of the workings of the vaccine court

4 Aug

This doesn’t involve the autism cases. Instead it is about the Hepatitis B omnibus proceeding which is also ongoing. It does involve some familiar names: Clifford Shoemaker (attorney), Dr. Mark Geier and his son David Geier. It does give us some insight into the billing practices of these gentlemen.

As background I’ll note that Clifford Shoemaker subpoenaed blogger Kathleen Seidel of Neurodiversity.com. He ended up being sanctioned for that action.

Dr. Mark Geier has been a frequent consultant to Mr. Shoemaker’s cases in the vaccine court. Ms. Seidel has covered some of the cases before where Dr. Geier has participated.

David Geier has so far not been compensated as a consultant to the Court.

In a recent case, Quinton O. Riggins, Jr. v. Secretary of HHS, we can see some of the decision processes involved in awarding fees to attorneys and consultants in the Court.

The application was for a total of $221,211.34:

On April 1, 2008, petitioner’s counsel, Clifford Shoemaker, filed an Application for Attorneys’ Fees and Costs (hereinafter referenced to as Petitioner’s Application), requesting a total of $221,211.34 in attorneys’ fees and costs. Counsel requests $16,592.16 in fees and costs related to the above-captioned matter, and $204,619.18 in fees and costs related to the “general hepatitis B proceedings.”

Of this, about $96k was paid:

Accordingly, petitioner is entitled to the following award for fees and costs for efforts in the Riggins case and for efforts on the hepatitis B cases in general: $95,801.72 for attorney’s fees and costs to be paid by check payable to petitioner and petitioner’s counsel; and $528.25 in petitioner’s costs to be paid by check payable to petitioner. The Clerk shall enter judgment accordingly.

The analysis of the application is lengthy. I will quote some sections below.

In regards to Mark and David Geier:

“Petitioner’s counsel requests $110,386.73 in costs related to S&A’s general hepatitis B work, of which counsel has earmarked $97,443.43 as costs (for fees and expenses) owed to Dr. Mark Geier and his son, David Geier.”

In the end, Dr. Mark Geier was paid $10,000 and David Geier was not compensated.

In denying payment to David Geier, who holds a bachelors degree, the Special Master noted:

“In summary, the undersigned finds the costs for David Geier’s efforts to be obviously unreasonable as Mr. Geier is not qualified to address the medical issues involved in the Program and his work was duplicative of the efforts by Dr. Geier. Thus, the undersigned denies the request for costs for David Geier in its entirety.”

In regards to Dr. Mark Geier:

However, Dr. Geier’s qualifications as an expert, testimony in the Program, and credentials, have been subject of considerable criticism over the years by the court. The undersigned questioned his expertise as far back as 1991. Daly v.Sec’y of HHS, No. 90-590V, 1991 WL 154573, at *7 (Cl. Ct. Spec. Mstr. July 26, 1991) (“[T]his court is inclined to not allow Dr. Geier to testify before it on issues of Table injuries. Dr. Geier clearly lacks the expertise to evaluate the symptomatology of the Table injuries and render an opinion thereon.”). More recently, in a published Order, my colleague, Special Master Vowell, addressed this criticism, as well as her concerns regarding petitioners utilizing medical articles authored by Dr. Geier, as follows:

I found that the articles authored by Dr. Geier unpersuasive and not scientifically sound, based on my prior reading of the articles and critiques of them. I am also aware that Dr. Geier is trained as a geneticist and obstetrician, not an immunologist, epidemiologist, or rheumatologist, and that my fellow special masters and several other judges have opined unfavorably on his qualifications and testimony as an expert.

It appears that since the Court has found that Dr. Geier is not qualified as an “expert”, he was retained as a “consultant”. However, he appears to have acted in ways overstepping the bounds of “counsultant”.

In the instant matter, the undersigned finds it was reasonable (and appropriate) for counsel to consult with Dr. Geier in a limited manner regarding the hepatitis B claims. Those efforts would entail Dr. Geier performing an initial review of the counsel’s hepatitis B claims and some initial research regarding vaccine injuries resulting from hepatitis B vaccine. Dr. Geier would then educate counsel as to the nature of the issues and the types of experts required. However, once Dr. Geier performed an initial review of these claims for counsel, and once counsel began reaching out to doctors who would ultimately serve as experts in S&A’s hepatitis B claims, it was no longer reasonable for Dr. Geier to be billing hours and incurring costs in S&A’s general hepatitis B efforts. Dr. Geier at this point was moving well beyond the role of a consultant.14 Thus by the beginning of 2002, when Mr. Shoemaker began to meet with experts15 to assist in the prosecution of the hepatitis B claims, Dr. Geier’s work on behalf of S&A’s general hepatitis B efforts was no longer needed and should have concluded.

Because of this, Dr. Geier was compensated at a reasonable amount for his consulting activities.

The undersigned notes an award of $10,000.00 represents an almost 90% reduction of the invoice submitted by the Geiers in this matter. The award of $10,000.00 is reasonable for Dr. Geier’s consultant efforts, and thus should not be viewed as a “reduction,” but viewed as reasonable compensation for Dr. Geier’s role as a consultant. The time not compensated is time largely spent by Dr. Geier duplicating the efforts of the experts, duplicating his own work, or performing work as an expert (work he is not qualified to perform). Stated another way, once experts were identified and became involved, Dr. Geier’s role as a consultant ended.

Mr. Shoemaker requested $221,211.34 in fees and costs:

On April 1, 2008, petitioner’s counsel, Clifford Shoemaker, filed an Application for Attorneys’ Fees and Costs (hereinafter referenced to as Petitioner’s Application), requesting a total of $221,211.34 in attorneys’ fees and costs. Counsel requests $16,592.16 in fees and costs related to the above-captioned matter, and $204,619.18 in fees and costs related to the “general hepatitis B proceedings.”

The court found that $64,254.45 was reasonable.

Here is an example of a charge that was denied:

The 5/30/2006 entry bills 0.5 hours to “[r]eview excel chart and update information; transfer information needed for SC to laptop,” P. App at 18. The “transfer information needed for SC to laptop” entry was explained by counsel asconstituting mere seconds and thus not administrative overhead. P Resp at 2, fn 1. However, counsel failed to address the remainder of the entry and identify what excel chart he was updating and how that activity was relevant to Mr. Riggins’ case. However, far more egregiously, counsel has billed for this exact same activity on precisely the same date twice before in two separate hepatitis B cases.

Trips to France and Italy were also excluded:

Another extreme example of counsel’s error in billing judgment is the request by counsel for fees and costs billed by Dr. Mark Geier and David Geier for trips to France and Italy in the summer of 2005 and winter of 2006 respectively, and for Mr. Shoemaker to travel to France with the Geiers in the summer of 2005. These requests represent a complete abdication of billing judgment.

Dr. Geier and Mr. Geier together billed a total of over $20,000.00, P App at 62-63, to travel along with Mr. Shoemaker to France and meet with various doctors and lawyers to discuss adverse events following the hepatitis B vaccination. Dr. Geier, in his affidavit, and counsel in Petitioner’s Sur-Reply, allege it was necessary to travel to France to discuss the doctors’ and lawyers’ experiences and research relating to adverse reactions stemming from the hepatitis B vaccination, and that this information could only be obtained in “face-to-face” discussions. In addition, Dr. Geier and Mr. Geier together billed $23,690.00 to travel to Italy to attend the 5th International Conference of Autoimmunity. Petitioner argues in Petitioner’s Response that the Geiers were invited to present their research at the conference by Dr. Shoenfeld, a leading expert in autoimmunity, and that at the conference they were able to secure Dr. Shoenfeld’s services as an expert in counsel’s cases. Petitioner further alleges the Geiers were able to discuss autoimmune disorders with experts at the conference and further “expedite the prosecution of various hepatitis b cases.” P Resp at 12.

and

Additionally, the Geiers provided absolutely no supporting documentation, such as receipts, to evidence the $9,399.68, see P App at 60, they allege they incurred in costs for airline tickets, other transportation costs, parking, hotel, “daily expenses,” food, and conference fees during these trips. P App at 61-62. By itself, this failure justifies not awarding these costs.

Many expenses for Mr. Shoemaker were questioned by the Special Master. Some based on the lack of adequate justification for the costs:

Petitioner’s counsel has failed to provide adequate information for the undersigned to determined exactly what the costs represent and whether or not the costs were reasonably incurred. No receipts are provided for any of these expenses. For example, for what did counsel pay costs to Federal Express? Who traveled to Boston and stayed at the Ritz Carlton? What expert was met with in Boston? Who traveled to Florida? And what attorney was met with in Florida?

Other expenses were considered to be “overhead”

Respondent objects to five hours of time billed by counsel for “‘meeting with consultants about scanning issues’” on April 19, 2000; one hour of time billed by counsel for “‘review[ing] computer breakdowns and update computer field’” on October 8, 2002; and three hours of time billed by counsel for a “consultation with Legal Nurses Association to discuss reviewing cases and preparing chronologies” on September 19 and 21, 2001. R Opp at 17; see also R Reply at 7. Respondent objects to these billings on the basis that the billings are administrative in nature, “more properly categorized as overhead” and would benefit “all petitioners represented by [counsel’s] firm.” Id. The undersigned agrees.

The entire decision is 37 pages long, detailing the requests for reimbursments, fees and costs.

Prof. DeSoto discusses mercury and autism

3 Aug

A recent issue of the journal Acta Neurobiologiae Experimentalis (ANE) focused upon autism. Not just autism, but autism causation with papers on vaccines, acetaminophen and, of course, mercury. The idea for this focus edition came from Professor Dorota Majewska who holds the EU Marie Curie Chair at the Institute of Psychiatry and Neurology in Warsaw, Poland. The authors for this focus issue are largely the same as those from a conference Prof. Majewska organized in 2008, Autism and Vaccinations.

One of the papers in the focus edition of ANE was the paper by Hewitson et al., that we have discussed at length here at LeftBrainRightBrain.

Another paper in this focus edition is Sorting out the spinning of autism: heavy metals and the question of incidence by M.C. DeSoto and R.T. Hitlan. DeSoto and Hitlan gathered some attention for a paper a few years back where they analyzed an existing data-set, that by Ip et al.. D’oC and Interverbal discussed this paper at the blog Autism Street, starting with A Tale Of Two Tails. In that piece, D’oC and Interverbal discuss the statistical analysis used by DeSoto and Hitlan. Prometheus at the Photon in the Darkness blog also discussed the DeSoto and Hitlan paper in Winter Potpourri. Pure Pedantry blog at ScienceBlogs also discussed this study in Mercury, Autism, and a Note on Scientific Honesty. Perhaps the best analysis of the original DeSoto and Hitlan paper was performed by EpiWonk, an epidemiologist.

The recent paper by DeSoto and Hitlan, Sorting out the spinning of autism: heavy metals and the question of incidence, is basically a review article. It has been touted as support for the mercury hypothesis with a commonly quoted phrase,

Fifteen were offered as evidence against a link between exposure to these metals and autism. In contrast, a sum of 43 papers were supporting a link between autism and exposure to those metals

I somehow doubt the authors intended the debate to boil down to counting papers. It would be a weak support, and rather ironic at that as this paper is placed in exactly the sort of journal that leads to large numbers of papers supporting the heavy-metal/autism link. The current DeSoto and Hitlan paper is in a focus issue on autism in ANE which selected papers which support autism as vaccine injury. Many papers on the mercury appear in lower impact journals and by authors such as the father-son team of Geier and Geier (which if I counted correctly account for 19 of the 43 articles on DeSoto and Hitlan’s list). If you are unfamiliar with that team, the neurodiveristy.com blog has many articles on the team such as Significant Misrepresentations: Mark Geier, David Geier & the Evolution of the Lupron Protocol (Contents).

That said, I was planning to avoid the recent DeSoto and Hitlan paper. It isn’t really new (adding to the number of articles on toxins and autism without adding to the knowledge base). I was going to avoid the paper, that is, until Prof. DeSoto gave an interview for the Age of Auitsm blog. I don’t understand why the Age of Autism considers Prof. DeSoto to be an expert on so many areas of autism and the environment. The breadth of her work is not great. Below is an exchange which shows what I mean. Prof. DeSoto was asked to comment on the recent study by Hewitson et al., comparing vaccinated and unvaccinated monkeys.

Q: There is a study published in Acta Neurobiologiae Experimentalis alongside yours that deals with vaccinated and unvaccinated primates. Do you have a reaction to the study or its conclusions?

Dr. DeSoto: All the primates were vaccinated, the difference was whether there was a heavy metal additive. This is a potentially important study. There are a few weaknesses that prevent strong conclusions. The size of the control group is small (apparently n=2). Given that rhesus neural development within the brain region of interest is not all that well documented, a larger control group would have been desirable. This weakness is acknowledged by the authors.

Isolating the infant monkeys shortly after birth is a significant change from normal environment. The severing of the maternal bond and being raised essentially alone (only visual contact was maintained with the peer infants) affects every aspect of development – including neural development. There is evidence that brain volume is specifically affected by isolation. The rearing situation in the study, in my mind, is not very comparable to normal development, especially if the outcome of interest includes brain volume.

That said, this is the only study that has compared the net effect of multiple vaccination additives on brain development. Above all, I have to editorialize and say this seems difficult to understand (that is – why is this the only study?). If some scientists and some parents question the safety of the vaccine schedule, such studies as this one are the way to investigate the concerns.

Now, the one study that exists (even if there are caveats that go with pilot research) suggests there are differences. Whether one is of the opinion that individually testing vaccines is as good as testing the combined effect or not – at this point it is imperative that additional studies be conducted on the additive effect of the full vaccine schedules.

To be clear and to repeat, if one thinks that the vaccines with additives given in close succession have no effect on neural development– this ought to be established empirically. One thing that I noticed in the study is the main effect for difference in brain volume (no time effect). It should be noted that this suggests the early administration of additive-containing vaccine (first four rounds) was a culprit of interest.

Prof. DeSoto did not take a careful look at the Hewitson et al. study. How do I know this? In the above interview, DeSoto states:

“All the primates were vaccinated, the difference was whether there was a heavy metal additive”

The paper states, “”Four infants were assigned to the unexposed study group and received saline injections according to the schedule in Table I””. The differences included the heavy metal additive, as well as all the ingredients that make a vaccine differ from saline.

What amazes me is that the interviewer at the Age of Autism missed that as well. Even though AoA has touted the Hewitson study greatly, they don’t appear to have read it closely.

This is not a minor detail. It is key to the study design and conclusions.

Another comment:

Given that rhesus neural development within the brain region of interest is not all that well documented

I think that Prof. DeSoto can be excused for not realizing that there is a study tracking the development of precisely the amygdala in macaques. This is because Hewitson et al. did not include that reference (which was easily found in a pubmed search).

“The size of the control group is small (apparently n=2)”

The control group was 4. One was excluded for “scheduling reasons” and the other for unknown reasons. This was a major problem with the study. Fatal, one might say, as the brain sizes of the control group didn’t grow between the two time periods tested (about 4 months and about 6 months of age) for the monkeys. At the same time, their amygdalas shrank. This was a big warning sign that something was amiss with the control subjects, but this was ingored by Hewitson, et al.. Based on this faulty premise, Hewitson et al. claimed that the brains and amygdalas of the vaccinated monkeys were on an abnormal growth path. It is amazing that Prof. DeSoto missed that.

A fact that I am not surprised that Prof. DeSoto missed is that in a previous IMFAR abstract on this group, Hewitson et al. came to the exact opposite conclusion: that the brains of the vaccinated monkeys did not grow as fast as the unvaccinated monkeys.

Back to the recent DeSoto and Hitlan paper. They make the following statement:

It is worth noting that there have been only three empirical articles directly comparing those with and without an ASD on mercury levels in the body to a control group of normally developing matched controls that report that report no link (Ip et al. 2004, Soden et al. 2007, Hertz-Piciotto et al. 2010). While, the most recent article appears to be the strongest, lacking any obvious errors or flaws (we think that this recent article does provide at least some legitimate evidence contradicting the hypothesis that autism and heavy metals are linked), the other two are seriously flawed.

In the end, this mention of the Hertz-Picciotto study is why I decided to write about the DeSoto piece, and in the process bring in the interview.

Part of what made the Hertz-Picciotto study strong was the fact that they controlled for fish consumption. Correct me if I am wrong, but I believe this is something that Ip did not do, nor did DeSoto and Hitlan in their re-analysis. I don’t see mention of fish consumption in the recent DeSoto and Hitlan paper.

Again, I’ll point out that the analysis by EpiWonk was thorough and clear. I wish he had published it. I don’t think consider fish consumption to state that the DeSoto/Hitlan re-analysis of the Ip data is likely not thorough enough to make the conclusions they draw.

The fact of the matter is, the Ip data just aren’t that profound. It was worthwhile to do a re-analysis given the errors in the Ip dataset and paper. But it was three years ago that DeSoto and Hitlan did their re-analysis. In the meantime, Hertz-Picciotto et al. have a better dataset and a more thorough analysis.

DeSoto and Hitlan editorialize a bit in their paper:

If a person has publicly staked his/her career on a certain position being right, it may become harder to keep a truly open mind, even when new data become available and even when the original intent was to be objective. A way this bias might manifest itself is an overstatement or slight misstatement of results. We feel that both sides have been guilty of this, and this happens when a person becomes so confident in the correctness of his/her own view that he/she no longer reviews evidence to the contrary. Unconscious bias may exist even in the best scientists.

This begs the question of whether DeSoto and Hitlan are as guilty of those they chide. Re-analyzing the Ip data is not staking their career on a certain position. Repeatedly publishing on such a limited dataset does make this reader start to question whether some piece of their reputation is now tied to this position. With apologies to Prof. DeSoto, but the fact that her misimpressions of the Hewitson et al. paper are skewed towards the mercury hypothesis makes me wonder even more.

The autism research community needs to have fresh eyes looking at questions and data. DeSoto and Hitlan did well to reanalyze the Ip data once the mistakes were shown. They just appear to this observer to have (a) overstated the interpretation of their analysis and (b) gotten very quickly in to exactly the sort of rut they accuse others of being in.

OSR pulled from the market….or is it?

3 Aug

Here on LeftBrainRightBrain we recently discussed a letter from Boyd Haley, Ph.D. announcing his decision to voluntarily remove his product, OSR #1 from the market. The letter from Mr. Haley stated (in part):

The product will not be available for sale after that date until new drug approval has been obtained. Please continue to access our website, http://www.ctiscience.com , for updates on OSR#1® in the future.

The CTI website is down, and has been for a few days. The message I get when try it is:

HTTP Status 404 –

type Status report

message

description The requested resource () is not available.

Two locations I checked are still selling OSR.

The Forrest Health site has the letter from Mr. Haley noting that he has pulled the product from the market. They not only let you buy it, but they require that you purchase 3 or more “Note: you must order at least 3 items”.

Living Well International has OSR on their site as well. In response to my email, they response to my email request, “Do you still have OSR#1 for sale?”, they responded “Yes we do. It is $60 for a box of 30”

I do wonder how long before someone decides to make his or her own batch of OSR. Mr. Haley has been quoted as stating it was not difficult. The published recipe for the chemical indicates a few potential concerns. First, the chemicals are themselves not without hazards.

Triethylamine

Liquid causes first degree burns on short exposure; [CHRIS] Corrosive to skin; [Quick CPC] Short-term exposure at high concentrations may cause pulmonary edema. [ICSC] A lachrymator; [CHEMINFO] Experimental animals exposed repeatedly to 100 ppm show evidence of liver, kidney, lung, and heart damage. [HSDB] A corrosive substance that can cause pulmonary edema; [ICSC]

Chloroform has relatively high LD50 values (the amount where 50% of exposed animals die). But the MSDS lists reproductive toxicity as:

Birth defects have been seen in rats and mice exposed by inhalation of chloroform at concentrations greater than 100 ppm in air. Ingestion of chloroform by pregnant laboratory animals has resulted in fetotoxicity but not birth defects, and only at levels causing severe maternal effects.

Isophthaloyl chloride is only listed as an eye/skin irritant. I won’t go down the list of all the chemicals. I think you get the idea. It is likely that a competent chemist with a reasonable laboratory (including a fume hood and access to nitrogen gas) could produce “bathtub OSR” reasonably safely. I frankly cringe at the thought of someone attempting this at home. I will add, the yield of the published process for producing this chemical is about 72% without optimization. This begs the question to me as to how clean the product is in this form.

Opportunity to help improve care services for adults with autism

30 Jul

A consultation to help improve care services and healthcare outcomes for adults with autism in England was launched today by Care Services Minister Paul Burstow.

This is the next step to help adults with autism live full and independent lives as equal and included citizens and follows the publication of the strategy for adults with autism: Fulfilling and rewarding lives.

The strategy sets a clear framework for all mainstream public sector services to support adults with autism and is backed up by the Autism Act 2009, the first ever condition specific legislation.

The 12-week consultation process seeks views from those with autism, their families, carers, representative organisations and all sectors of society on a number of important issues such as:

*diagnosis of autism

*increasing awareness of autism amongst frontline staff

*provision of training and specialist training for frontline staff

*appropriate assessment of needs for those with autism

*provision of relevant services for young people and adults with autism

*local leadership for NHS and social care in relation to the provision of services for adults with autism

Care Services Minister Paul Burstow said:

“I hope people will take part in this opportunity to influence the direction and progress of our autism programme.

“It is unacceptable when adults with autism do not get the right care and support they need from health and social care services.

“The Government wants the consultation to reach as many people as possible, in line with our goal of giving people more say in the decisions that affect their lives. These views will help shape our priorities as we seek to help adults with autism live fulfilling and rewarding lives.”

Mark Lever, Chief Executive of the National Autistic Society, said:

“This is the vital next step people with autism and their families have been waiting for. During the passage of the Autism Act, Parliament described this statutory guidance as the ‘teeth’ of the Act, so it is vital that it secures real and lasting change at ground level.

“Now, I’d like to urge as many adults with autism, their parents and carers to take part in the consultation to make sure it is robust and can be used to hold their local services to account. The right support at the right time can make an enormous difference to peoples’ lives.”

The statutory guidance for health and social care will be published by December 2010. The strategy will be reviewed in 2013.

Go to http://www.dh.gov.uk/en/Consultations/Liveconsultations/DH_118058 for info packs.

Give the IACC your input on what autism research should focus upon

28 Jul

I’ve already blogged this a few times. The deadline is coming soon, July 30th. The IACC listens to public input. Whatever you think should be stressed or not stressed in autism research, let the IACC know now.

The link for the input form is here

They allow you to give very extensive responses. Don’t let this put you off. If you only have a couple comments, give them. Do it now.

Autistic adult left in van on hot day, dies of exposure

28 Jul

I have a real hard time discussing these events. The story Woods Services client dies in van appeared on a site called PhillyBurbs.com. Here are the opening paragraphs:

Middletown police are investigating the death of a 20-year-old Woods Services resident with severe autism who was left inside a van parked on the campus for more than five hours on the hottest day of the year.

Brian Nevins, originally from Queens, N.Y., died of hyperthermia Saturday after he returned with several others from a day trip to the Sesame Place theme park, said Bucks County Coroner Dr. Joseph Campbell.

An example of how alternate vaccine schedules endanger children

28 Jul

With apologies–this post has nothing to do with autism except in pointing out where groups like Generation Rescue give out bad advice.

There is an outbreak of pertussis (whooping cough) in California right now. It looks to be a major outbreak, possibly the largest in fifty years–since vaccination was implemented.

Generation Rescue has a number of alternative vaccine schedules that they promote on their website. Their “favorite” schedule was created by a doctor named Donald Miller. Let’s look at it, shall we:

In summary, this is a vaccination schedule that I would recommend:

1. No vaccinations until a child is two years old.
2. No vaccines that contain thimerosal (mercury).
3. No live virus vaccines (except for smallpox, should it recur).
4. These vaccines, to be given one at a time, every six months, beginning at age 2:
1. Pertussis (acellular, not whole cell)
2. Diphtheria
3. Tetanus
4. Polio (the Salk vaccine, cultured in human cells)

*No vaccinations until a child is two years old.* That’s right, don’t vaccinate infants. The deaths in California so far are for children under the age of 6. Dr. Miller’s schedule, the one most recommended by Generation Rescue, would leave children vulnerable to pertussis until at least age 2.

This is just plain dangerous advice.

It isn’t even well thought out. Not in the least. The reason is found in the FDA list of vaccines licensed in the U.S.. You can take a look or you can take my word for it: there is no single pertussis vaccine available.

It is impossible to follow Generation Rescue’s favorite vaccine schedule, which calls for a single pertussis vaccine to be given after age 2.

Even Dr. Sears acknowledges that (a) pertussis is a vital vaccine to give to infants and (b) you can’t get pertussis as a single vaccine. (also, (c) he sees rotavirus as an “immediate danger” to babies and children, contrary to the position of Generation Rescue).

Diseases that don’t exist in the U.S. or that don’t occur during infancy in the U.S. (so even though they can be very severe, a child has almost no risk of catching it in the U.S.) that could be safely delayed are polio, Hep B, tetanus, and diphtheria (although to get a pertussis vaccine, tetanus and diphtheria have to come along with it).

Diseases that DO pose an immediate danger to babies and children are HIB and PC meningitis, Rotavitus, and Pertussis. So, I would rather children stay on time with those four vaccines and delay the flu shots (if you feel comfortable delaying flu shots).

The whooping cough epidemic is getting a lot of coverage in the press. Just today, Dr. Nancy Snyderman of the Today Show discussed this:

Visit msnbc.com for breaking news, world news, and news about the economy

Dr. Snyderman has a lot of good points, including the fact that there are immune compromised people in the community are at risk from the spread of diseases like pertussis.

Dr. Snyderman also makes a mistake in the interview. She claims that children died of measles in the U.S. last year. Watch for groups like the Age of Autism to ignore all the facts and concentrate on that mistake.

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