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A multicenter blinded analysis indicates no association between chronic fatigue syndrome/myalgic encephalomyelitis and either xenotropic murine leukemia virus-related virus or polytropic murine leukemia virus

19 Dec

There was much discussion of the possible imprtance of the xenotropic murine leukemia virus-related virus (XMRV) in conditions such as chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME), prostate cancer and autism. To be clear, the possibility of an autism association was made in the press, not in the research literature. For XMRV in general, there was much discussion in the press, in journals and online as it became clear over time that there were possible problems with the analyses that led to the main papers on the topic. The present study includes work by a multi-site team including the principle author of the original study linking XMRV with CFS/ME.

If one can boil a large, multi-site study result into one line, it would be this:

Here, the original investigators who found XMRV and pMLV (polytropic murine leukemia virus) in blood of subjects with this disorder report that this association is not confirmed in a blinded analysis of samples from rigorously characterized subjects

I.e. there is no link between XMRV and CFS/ME.

Here is the abstract, and the full paper is online as well:

The disabling disorder known as chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) has been linked in two independent studies to infection with xenotropic murine leukemia virus-related virus (XMRV) and polytropic murine leukemia virus (pMLV). Although the associations were not confirmed in subsequent studies by other investigators, patients continue to question the consensus of the scientific community in rejecting the validity of the association. Here we report blinded analysis of peripheral blood from a rigorously characterized, geographically diverse population of 147 patients with CFS/ME and 146 healthy subjects by the investigators describing the original association. This analysis reveals no evidence of either XMRV or pMLV infection. IMPORTANCE Chronic fatigue syndrome/myalgic encephalomyelitis has an estimated prevalence of 42/10,000 in the United States, with annual direct medical costs of $7 billion. Here, the original investigators who found XMRV and pMLV (polytropic murine leukemia virus) in blood of subjects with this disorder report that this association is not confirmed in a blinded analysis of samples from rigorously characterized subjects. The increasing frequency with which molecular methods are used for pathogen discovery poses new challenges to public health and support of science. It is imperative that strategies be developed to rapidly and coherently address discoveries so that they can be carried forward for translation to clinical medicine or abandoned to focus resource investment more productively. Our study provides a paradigm for pathogen dediscovery that may be helpful to others working in this field.

There was a lot of hope in the CFS/ME community that this was a breakthrough that could lead to a treatment. Unfortunately, the answers they seek are elsewhere.

As this is an autism-focused site, allow me to bring this back to autism. Unlike CFS/ME, there were no papers claiming an association between autism and XMRV. Instead there were public comments by the researcher involved and inflammatory journalism. In a search for XMRV autism the first article I get is: Is Autism Associated with A Viral Infection?, by David Kirby published at the Huffington Post. Mr. Kirby’s article was probably the first that pushed the (now failed) XMRV/autism hypothesis strongly into the public’s eye. Mr. Kirby was well known for some time previous for his work promoting the idea that vaccines cause autism. In specific, he was a major proponent of the idea that thimerosal in vaccines caused autism, having published a book Evidence of Harm: Mercury in Vaccines and the Autism Epidemic. For his Huffington Post article on XMRV, Mr. Kirby had some rather irresponsbile speculations from XMRV researcher Judy Mikovits and the founder of her reseach institute Annette Whittemore. From those quotes, Mr. Kirby proceeded to present the XMRV news story in his own way, as a series of speculative questions to create an impression built like a house of cards. The impression he left the reader with was that the XMRV story helped to explain a possible link between autism and vaccines. Following a quoted statement by Mikovits, Mr. Kirby wrote

So there you have it – a possible explanation of regressive autism in a significant number of cases associated with immune system deregulation triggered by vaccination.

Of course, much more work is needed to nail down the exact significance of such an association. For example, is the virus implicated in the cause of autism, or do children harbor the virus as a result of autism?

Notice that he doesn’t say, “much more work is needed to show that this is a real association“. No, rather than stress again that the hypothesis was poorly supported, he jumps to assuming the association and asking what significance it has. Classic David Kirby.

To be fair, the comments by Mikovits and the founder of the research center where she worked (Annette Whittemore) fed directly into his story. To say it again, those statements by Mikovits and Whittemore were irresponsible given the early stage this work was in. But even with those statements, Mr. Kirby had no justification to go into this speculative paragraph:

The discovery raises more questions than it answers. What, exactly, is it about immunization that might switch on XMRV viral expression? Could the effect of heavy metals upon cytokine balances be at play? Where did this retrovirus come from, and how did it apparently become so prevalent in children with autism? Did these children inherit the virus from a parent, or was there some other unexplained route of transmission? Why has the NIH said nothing about XMRV in association with autism, and did Dr. Insel know about these findings without sharing them with the IACC

Again, we see the series-of-questions approach that is Mr. Kirby’s style. He isn’t saying immunization switches on XMRV viral expression (whatever he meant by “XMRV viral expression”. It sounds technical though). He’s posing it as a question. Notice how he brought in his mercury hypothesis, but as “heavy metals”. “Could the effect of heavy metals upon cytokine balances be at play?”. This is a great example of a sciency-sounding sentence that has no substance. Whoever was his editor at the Huffington Post should have shot that back with “do you even know what your talking about here?” But if the editor at the Huffington Post was doing his/her job, this article (and many more by Mr. Kirby) wouldn’t have been published there anyway. It is worth noting that by the time this article was written, the evidence was overwhelmingly against the idea that mercury in vaccines raised autism risk, but this was Mr. Kirby’s way of loosely tying his failed hypothesis to his then current speculation.

To pull the last sentence out of Mr. Kirby’s paragraph: “And why had the NIH said nothing about XMRV?”. Perhaps because they were more responsible than Mr. Kirby.

As a point of fact, XMRV is not prevalent in autistics (Lack of infection with XMRV or other MLV-related viruses in blood, post-mortem brains and paternal gametes of autistic individuals and PCR and serology find no association between xenotropic murine leukemia virus-related virus (XMRV) and autism.) In fact, as will be discussed below, it appears to not infect humans. Unfortunately, Mr. Kirby has not seen fit to post corrections. To the XMRV story or others.

The impression Mr. Kirby created with his story was strong. For example, he gathered 298 comments to his article, largely focused on vaccines. Here’s the last one, prominently at the top of the list:

David: As big as this autism story is, it is only one toe of the elephant. Here is another: There are no protections in place to prevent more XMRV from entering the nation’s blood supply. There is as of yet no XMRV screening test for donated blood. And — I just called my local Red Cross – there is as of yet nothing to prevent people diagnosed with CFS from donating blood. We are all at risk.

The elephant: How did our government let this potentially deadly retrovirus spread unchecked for twenty-five years? XMRV has, so far, now has been found to occur in people with autism, lymphoma, a severe form of prostate cancer, atypical MS, ME/CFS, and fibromyalgia. Twenty-three years ago the CDC was first informed of an outbreak of what we now know to be an XMRV-associated local epidemic. Eighteen years ago a study showed a retrovirus was associated with ME/CFS.

The band played on.

Yes, let’s spread fear about the blood supply, based on news reports, speculation and bad science.

Some of the authors of this present XMRV and CFS/ME study were also involved in a separate major multisite study on MMR and autism. I am referring to a study intended to replicate the key findings of some of Andrew Wakefield’s research. That study, by Mady Hornig, W. Ian Lipkin and others, Lack of association between measles virus vaccine and autism with enteropathy: a case-control study been re-interpreted by some as supporting Mr. Wakefield’s work. Some have gone so far as to claim that Mr. Lipkin’s team is signalling support for Mr. Wakefield’s work by citing it in other studies. It’s a stretch, a mind boggling stretch, and it’s wrong.

From the CFS/ME paper:

Sensitive molecular methods for microbial discovery and surveillance have enabled unique insights into biology and medicine. However, increased sensitivity for bona fide signal increases the risk that low-level contaminants may also be amplified. This can lead to spurious findings that pose challenges for public health and require an expensive and complex pathogen dediscovery process. Examples wherein authors of this paper have been engaged in this process include refutation of associations between enterovirus 71 and amyotrophic lateral sclerosis (24) and MMR vaccine and autism (25).

Lipkin and Hornig consider their work to be a “refutation” of the association between MMR and autism. But don’t take that one sentence from the paper as the only proof. Here’s an interveiw with Prof. Lipkin at Nature.

Had we done this when Andrew Wakefield [the former medical researcher who proposed that autism was caused by vaccines] came out with the initial report about the measles, mumps and rubella (MMR) vaccine and autism, and had something this definitive, there are many more children who would have been vaccinated against measles during the ten years it took us to finally complete the MMR–autism work. So I think it’s crucial that we don’t do things in a half-baked fashion, so we can test hypotheses and move on to new ones.

The interviewer even includes the MMR refutation as part of a question: “You have disproved the autism–MMR connection and other controversial disease links.”

In general, what can one say about XMRV? Aside from the drama involved in the story (which I did not discuss in detail in this article), and the questions about CFS/ME, autism, prostate cancer and more, what can we say? Prof. Lipkin says it very clearly in the interview:

We did not find any genetic sequences [of XMRV or related viruses] in the people with CFS or the controls. As far as we know, there is no human being that is infected with XMRV.

But there were papers (some now retracted) claiming some links between XMRV and human disease? What about those? Another quote pulled from the interview:

I think the explanation is that there was contamination. I don’t see any reason to invoke anything beyond that.

For this you have to give Judy Mikovits some credit. She worked with the team that was attempting to replicate her results. Contrast this with, say, Andrew Wakefield. A man whose hospital offered him the opportunity to replicate his own results, and he quit rather than accept that offer. A man who has repeatedly denied the science which has been clearly against his hypothesis. A man who denies the fact that he acted unethically in many ways in conducting his research. Judy Mikovits made some mistakes, both scientific and socially, but she seems to be part of the solution.

But that’s a bit of a sideshow. The main conclusion is that XMRV is not involved with autism. Or, apparently, any human disease.

With apologies for revisiting David Kirby and Andrew Wakefield.

—
By Matt Carey

AAP opposes worldwide ban on thimerosal

17 Dec

In a series of articles released today, the American Academy of Pediatrics outlines its opposition to a proposed UN treaty which, if approved, would ban the preservative thimerosal from vaccines worldwide. The ban is also opposed by the World Health Organization and the US Public Health Service. It is estimated that multidose vaccines with thimerosal as a preservative are used in 120 countries to immunize approximately 84 million children, saving about 1.4 million lives each year.

The AAP’s opposition reverses the professional organization’s call in 1999 for the removal of thimerosal from the US pediatric vaccine schedule. That action is frequently cited by anti-vaccine groups as evidence that health officials know that vaccines cause autism and other neurological conditions. But Dr. Louis Z. Cooper and Dr. Samuel L. Katz, co-authors of  one of today’s articles, directly take on that concern:

Had the AAP (and, we suspect, the USPHS) known what research has revealed in the intervening 14 years, it is inconceivable to us that these organizations would have made the joint statement of July 7, 1999. The World Health Organization recommendation to delete the ban on thimerosal must be heeded or it will cause tremendous damage to current programs to protect all children from death and disability caused by vaccine-preventable diseases.

The 1999 domestic ban surfaced during a Nov. 29 congressional hearing on autism, where representatives of both parties repeated long-debunked anti-vaccine talking points. Rep. John Tierney (D-MA) asked the CDC’s Dr. Colleen Boyle why thimerosal was taken out of childhood vaccines if there were no concerns about its safety. Boyle wisely agreed to get back to him with an answer. An anti-vaccine hearing is no place for reasoned discussion.

In another article, researchers Katherine King, PhD, MSc; Megan Paterson, and Shane K. Green, PhD; reaffirm that “there is no credible scientific evidence that the use of thimerosal in vaccines presents any risk to human health.” They continue:

Extensive pharmacologic and epidemiological research has shown early, theoretical concerns about links to autism or other neurodevelopmental disorders to be false. Indeed, the exculpatory strength of the data now available on thimerosal is well evidenced by recent statements from the Global Advisory Committee on Vaccine Safety, US Institute of Medicine, and American Academy of Pediatrics, all of which have concluded that thimerosal exposure through vaccination is not harmful to human health.

The AAP’s latest action is a shot across the bow to anti-vaccine groups. The UN’s proposed thimerosal ban has been championed by Mark Geier, the disgraced Maryland geneticist best known for chemically castrating disabled children. Two years ago, he told a group of African delegates gathered for a session of the Intergovernmental Negotiating Committee in Japan that thimerosal “is favored by the pharmaceutical industry because it is cheap and enables the industry to keep making vaccines in old and dirty factories.”

Geier is a regular at Jenny McCarthy’s annual anti-vaccine conference, where he receives standing ovations from anti-vaccine parents. Ten states have either revoked his medical license over the last two years, or allowed it to expire, for Geier’s ethical lapses which included lying about his qualifications risking children’s health with unproven medical treatments.

—
By AutismNewsBeat

DSM 5 has been approved

1 Dec

Below is the announcement that the DSM 5 has been approved. No details on the approved criteria for autism. I found the link to the original posted to Facebook by the Autism Science Foundation.

A Message From APA President Dilip Jeste, M.D., on DSM-5

December 1, 2012

I am pleased to announce that DSM-5 has just been approved by APA’s Board of Trustees. Getting to the finish line has taken a decade of arduous work and tens of thousands of pro-bono hours from more than 1,500 experts in psychiatry, psychology, social work, psychiatric nursing, pediatrics, neurology, and other related fields from 39 countries. We look forward to the book’s publication next May.

The goal of the DSM-5 process has been to develop a scientifically based manual of psychiatric diagnosis that is useful for clinicians and our patients. APA’s interest in developing DSM dates back to the organization’s inception in 1844, when one of its original missions was to gather statistics on the prevalence of mental illness. In 1917, the Association officially adopted the first system for uniform statistical reporting called the Statistical Manual for the Use of Hospitals for Mental Diseases, which was adopted successfully by mental hospitals throughout the country. It was expanded into the first Diagnostic and Statistical Manual (DSM) in 1952 and first revised (DSM-II) in 1968. Like the rest of the field in that era, these first two versions were substantially influenced by psychoanalytic theories.

With advances in clinical and scientific knowledge, changes in diagnostic systems are inevitable. The World Health Organization’s International Classification of Diseases (ICD)—the standard diagnostic tool for epidemiology, health management, and clinical care used around the world, which covers all medical diagnoses—has been through 10 editions since the late 1800s and is now preparing its 11th edition, due in 2015. Likewise, DSM has undergone changes to take into account progress in our understanding of mental illnesses. DSM-III, published in 1980 under the leadership of Dr. Robert Spitzer, and DSM-IV, published in 1994 under the leadership of Dr. Allen Frances, represented the state of science of psychiatry at those times and significantly advanced the field.

In the two decades since the publication of DSM-IV, we have witnessed a wealth of new studies on epidemiology, neurobiology, psychopathology, and treatment of various mental illnesses. So, it was time for APA to consider making necessary modifications in the diagnostic categories and criteria based on new scientific evidence. But there were, of course, challenges inherent in revising an established diagnostic system The primary criterion for any diagnostic revisions should be strictly scientific evidence. However, there are sometimes differences of opinion among scientific experts. At present, most psychiatric disorders lack validated diagnostic biomarkers, and although considerable advances are being made in the arena of neurobiology, psychiatric diagnoses are still mostly based on clinician assessment.

Also, there are unintended consequences of psychiatric diagnosis. Some arise from the unfortunate social stigma and discrimination in getting jobs or even obtaining health insurance (notwithstanding the mental health parity law) associated with a psychiatric illness. There is also the double-edged sword of underdiagnosis and overdiagnosis. Narrowing diagnostic criteria may be blamed for excluding some patients from insurance coverage and needed services, while expanded efforts to diagnose (and treat) patients in the early stages of illness to prevent its chronicity are sometimes criticized for increasing its prevalence and potentially expanding the market for the pharmaceutical industry. (It should be noted, however, that DSM is not a treatment manual and that diagnosis does not equate to a need for pharmacotherapy.)

APA has carefully sought to balance the benefits of the latest scientific evidence with the risks of changing diagnostic categories and criteria. We realize that, given conflicting views among different stakeholders, there will be inevitable disagreements about some of the proposals— whether they involve retaining the traditional DSM-IV criteria or modifying them.

The process of developing DSM-5 began in earnest in 2006, when APA appointed Dr. David Kupfer as chair and Dr. Darrel Regier as vice chair of the task force to oversee the development of DSM-5. The task force included the chairs of 13 diagnostic work groups, who scrutinized the research and literature base, analyzed the findings of field trials, reviewed public comments, and wrote the content for specific disorder categories within DSM-5. To ensure transparency and reduce industry-related conflicts of interest, APA instituted a strict policy that all task force and work group members had to make open disclosures and restrict their income from industry. In fact, the vast majority of the task force and work group members had no financial relationship with industry.

To obtain independent reviews of the work groups’ diagnostic proposals, the APA Board of Trustees appointed several review committees. These included the Scientific Review Committee (co-chaired by Drs. Ken Kendler and Robert Freeman), Clinical and Public Health Committee (co-chaired by Drs. Jack McIntyre and Joel Yager), and APA Assembly Committee (chaired by Dr. Glenn Martin). Additionally, there was a forensic review by members of the Council on Psychiatry and Law. Drs. Paul Appelbaum and Michael First were consultants on forensic issues and criteria/public comments, respectively. Reviews by all these groups were coordinated in meetings of the Summit Group, which included the task force and review committee co-chairs and consultants along with members of the Executive Committee of the Board of Trustees

There has been much more public interest and media scrutiny of DSM-5 than any previous revisions. This reflects greater public awareness and media interest in mental illness, as well as widespread use of the Internet and social media. To facilitate this transparent process, APA created a Web site (www.dsm5.org) where preliminary draft revisions were available for the public to examine, critique, and comment on. More than 13,000 Web site comments and 12,000 additional comments from e-mails, letters, and other forms of communication were received. Members of the DSM-5 work groups reviewed the feedback submitted to the Web site and, where appropriate, made modifications in their proposed diagnostic criteria.

We believe that DSM-5 reflects our best scientific understanding of psychiatric disorders and will optimally serve clinical and public health needs. Our hope is that the DSM-5 will lead to more accurate diagnoses, better access to mental health services, and improved patient outcomes

—

By Matt Carey

Complementary and alternative medicine use in a large pediatric autism sample

9 Nov

The journal Pediatrics has a large number of autism related articles in a recent supplement. One of these covers a topic discussed a great deal by parent groups online: alternative medical approaches to the treatment of autism. In Complementary and alternative medicine use in a large pediatric autism sample, James Perrin (this one of his five articles in the Supplement; Dr. Perrin is the president elect of the American Academy of Pediatrics) and his coauthors use the Autism Treatment Network (ATN) to review parent report of use of complementary and alternative medicine (CAM) in regards to autism.

The authors find that while CAM is used by a significant minority of parents, it is a minority: 28% (896 out of 3173). Special diets are the most common (548 respondents, 17%). Various methodologies are listed below:

Characteristic N
Any CAM 896
Special diets 548
Gluten-free diet 249
Casein-free diet 289
No processed sugars 69
No sugars or salicylates 28
Feingold diet 14
Other specified special diet 293
Other CAM 643
Other vitamin supplements 413
Probiotics 274
Essential fatty acids 171
Digestive enzymes 116
Higher dosing vitamin B6 and magnesium 99
Chiropractic 77
Amino acids 59
Antifungals 58
Glutathione 33
Chelation 19
Hyperbaric oxygen 12
Acupuncture 10
Sulfation 7
Other specified CAM 173

Some of the most talked about methodologies are rarely used. Chelation, for example, had only 19 respondents or 0.6%. Hyperbaric oxygen, 0.4%. Previously, chelation had been reported as being used by about 7% of families. If these studies are comparable, this would indicate that chelation has dropped from low to very low in use by parents.

CAM usage is higher among the wealthy, whites, those with children with autism vs PDD NOS or Asperger syndrome, and higher among those whose children have gastrointestinal complaints and/or seizures. The authors note:

As with other CAM use, it will help to determine more about the potential synergistic effects of CAM with medical treatments as well as ways that CAM use may interfere with improvement in medical conditions.

The full article is available free online including a discussion of limitations of the study. The abstract is copied below:

BACKGROUND AND OBJECTIVE Children and adolescents with autism spectrum disorder (ASD) often use complementary and alternative medicine (CAM), usually along with other medical care. This study aimed to determine associations of ASD diagnostic category, co-existing conditions, and use of medications with use of CAM.

METHODS We used the Autism Speaks Autism Treatment Network patient registry, which collects information on CAM use, medical conditions, and psychotropic medication at enrollment. CAM was categorized as special diets versus “other” CAM; ASD was defined as autism, pervasive developmental disorder (PDD), or Asperger’s. Gastrointestinal symptoms, seizure disorders, sleep problems, and medication use were determined from parent report. Child Behavior Checklist (CBCL) scores were used to measure behavioral symptoms. Logistic regression was used to determine associations of diagnostic category, other medical conditions, and medication use with CAM treatments, controlling for demographic characteristics.

RESULTS Of 3413 subjects in the registry as of April 2011, 3173 had complete data on CAM use: 896 (28%) reported any use; 548 (17%), special diets; and 643 (20%), other CAM. Higher rates of CAM use were associated with gastrointestinal symptoms (odds ratio [OR] = 1.88), seizures (OR = 1.58), and CBCL total score >70 (OR = 1.29). Children with PDD (OR = 0.62), Asperger’s (OR = 0.66), or using medications (0.69) had lower rates.

CONCLUSIONS Children with ASD use more CAM when they have co-existing gastrointestinal symptoms, seizure disorders, and behavior problems. This study suggests the importance of asking about CAM use in children with ASD, especially those with complex symptoms.

Controversial autism doctor Mark Geier loses licenses in Missouri, Illinois

4 Nov

Mark Geier has been discussed a great deal here on Left Brain/Right Brain. Including very recently on the topic of this article. Much of that discussion has recently centered on his belief that not only is autism caused by mercury, but that mercury somehow is bound to testosterone and that by reducing the amount of testosterone in the body one can reduce the amount of mercury and, thus in his flawed model, treat autism. Mr. Geier’s clinical practice was found to have been flawed as well and he lost his license to practice medicine in his home state of Maryland. He was licensed in multiple other states as well, including Missouri and Illinois. With the loss of his license in Maryland, other states have followed in license actions.

The St. Louis Post Dispatch reports: ” Controversial autism doctor Mark Geier loses licenses in Missouri, Illinois”.

Todd W. Of Harpocrates Speaks writes about this in “Mark Geier on his Last Leg” where he notes that Mark Geier is still licensed in Hawai’i only.

Todd W. keeps a map of states where Mark Geier has lost his license.

—
By Matt Carey

Hyperbaric oxygen in the treatment of childhood autism: a randomised controlled trial

24 Oct

Hyperbaric Oxygen therapy (HBOT) has risen in recent years as an “alternative” therapy for many conditions, autism included. The logic behind HBOT is rather fuzzy. For example, there was some discussion of using HBOT to reduce oxidative stress a few years back. How increasing oxygen in the body would decrease oxidative stress was not clear. Some other discussions focused on oxygen perfusion. Basically, some studies have shown that some areas of the brain may be getting less oxygen in autistics than in non-autistics. The idea was that increasing the oxygen to those areas might result in some improvement in some measure or another.

This begs the question: are there areas of higher perfusion (hyperperfusion) in the brains of autistics? Seems an important question to pose when proposing increasing perfusion. But one can not find the term “hyperperfusion” in this review promoting HBOT and autism, for example. But the answer is, yes, people have measured hyperperfusion in autistic’s brains:

Brain perfusion SPECT and EEG findings in children with autism spectrum disorders and medically intractable epilepsy

In specific, they found

The areas of hypoperfusion and EEG focus were highly related in seven of 12 children, while the areas of hyperperfusion were highly related to EEG focus in six of 12 children. The areas of hypoperfusion were highly related to the focus observed on EEG, but were not always related.

Using the simplistic logic of HBOT/autism promotors, one then is left with the question of whether could HBOT make seizure activity worse? I wouldn’t put too much weight on this question other than to point out that it isn’t 100% clear that there can be no downside to HBOT. The logic “there is hypoperfusion therefore HBOT should benefit” isn’t strong; the idea that “there are areas of hyperperfusion, therefore HBOT could have a downside” is also not strong. There are three other studies mentioning hyperperfusion and autism. And, I was interested to see that there are 350 hits for a search of hyperperfusion and epilepsy in pubmed. Compare this to 30 hits for autism and hypoperfusion.

Back to HBOT. There isn’t much science for HBOT, to be frank. Most of the momentum, at least in publications, is from one source: Dan Rossignol. An early paper: Hyperbaric oxygen therapy may improve symptoms in autistic children. by Dr. Rossignol was published in Medical Hypotheses–a pseudo medical journal. I believe Dr. Rossignol’s clinic in Florida provides HBOT.

While there have been articles like the above and some small open label study reports, true randomized trials have been lacking. A recent review Hyperbaric oxygen therapy for treatment of children with autism: a systematic review of randomized trials reported

While some uncontrolled and controlled studies suggested that HBO therapy is effective for the treatment of autism, these promising effects are not replicated. Therefore, sham-controlled studies with rigorous methodology are required to be conducted in order to provide scientific evidence-based HBO therapy for autism treatment.

Also worth noting is that HBOT is currently rated as “non-accepted” by the European Committee for Hyperbaric Medicine. An indication that there was not good evidence either way at the time they prepared their statement.

Two recent studies (the one which is the focus of this article and another) have used a more randomized/blind methodology and one has looked at biomarkers considered important in HBOT and autism (cytokines). The results have not been encouraging.

First the more biomarker based study. This group studied autistic children given HBOT and looked at cytokine levels (Brief report: Hyperbaric oxygen therapy (HBOT) in children with autism spectrum disorder: a clinical trial.) Per that study,

Ten children completed 80 sessions of HBOT and all improved by 2 points on the clinician-rated CGI-I scale (much improved) as well as several parent-completed measures of behavior. The lack of a control group limits the ability to determine if improvements were related to HBOT.

and also:

“Although this study was limited by the small sample size and by the variable nature of cytokines, we found no evidence that HBOT affects cytokine levels or that cytokine levels were associated with behavioral changes”

So, if there is a benefit from HBOT, it isn’t due to changes in cytokines. Which HBOT doesn’t seem to affect.

Another somewhat recent study attempted a clinical trial as well
Controlled evaluation of the effects of hyperbaric oxygen therapy on the behavior of 16 children with autism spectrum disorders. This study, out of the old “Thoughtful House” including Andrew Wakefield as an author found ” No consistent effects were observed across any group or within any individual participant, demonstrating that HBOT was not an effective treatment for the participants in this study. This study represents the first relatively large-scale controlled study evaluating the effects of HBOT at the level of the individual participant, on a wide array of behaviors.”

Finally, a study out in the past couple of months again attempts a randomized controlled study: “Hyperbaric oxygen in the treatment of childhood autism: a randomised controlled trial.” The study is out of Thailand. One factor of note is the attempt to do a real control using a “sham” air group. Obviously HBOT studies are complicated in that study subjects can easily detect the changes in pressure. Of note, HBOT in this case is 100% oxygen:

This study was a prospective, randomised, double-blind, controlled trial of HBOT at 153 kPa (1.5 ATA) with 100% oxygen for one hour daily, weekdays to a total of 20 sessions, versus a sham air treatment consisting of pressurised room air at 116 kPa (1.15 ATA) on the same schedule.

While some reports have used 100% oxygen at 1.5ATA, many have used either air or enriched air and sometimes lower pressure (1.3ATA). I.e. this study involves higher oxygen exposure than in many studies. Air is about 21% oxygen. So, a 1.5 atmospheres of pure oxygen is about 7.5 times the oxygen partial pressure in air. Many reports in early studies were about 1.3 ATA air or slightly enriched air. 1.3 ATA (atmospheres absolute) at 25% O2 is about 32% oxygen. For divers, these levels of oxygen are comparable to Nitrox or enriched air. One can get a higher oxygen level from a mask at 1 atmosphere. Which has been a critique of HBOT from the start. Early anecdotal reports from HBOT practitioners claimed that oxygen delivered by mask was not effective. Only high pressures gave whatever results were claimed. Which is counter intuitive to the simple explanations of how HBOT should work.

But, with both high pressure and pure O2, the Thailand study should provide clarity in these questions. Which begs the question, what are those results? The full paper is online and the abstract is below.

BACKGROUND:
Promising results with hyperbaric therapy for children with autism have been reported, but most involved the use of only mild pressure with oxygen supplementation. To date, there has been no randomised, blinded trial of 100% oxygen administered at hyperbaric pressure. This study evaluated the efficacy of hyperbaric oxygen therapy (HBOT).

METHODS:
Sixty Thai children with autism, aged three to nine years, were randomly assigned to receive 20 one-hour sessions of either HBOT at 153 kPa (1.5 ATA) or sham air at 116 kPa (1.15 ATA). Effects on behaviour were measured using the Autism Treatment Evaluation Checklist score (ATEC) and clinical improvement was measured with the Clinical Global Impression (CGI) system; in particular the clinical change (CGIC) and severity (CGIS) sub-scores. These were evaluated by parents and clinicians, both of whom were blinded to the actual exposure.

RESULTS:
The mean total ATEC scores by both parents and clinicians were significantly improved after intervention in both arms of the study compared to the score before intervention (P <; 0.001 in both groups by parents, P = 0.015 in HBOT group and P = 0.004 in sham group by clinician). There were no statistically significant differences in average percentage changes of total ATEC score and all subscales scores when comparing the HBOT and sham air groups, either by parents or clinicians. Changes in the CGI scores following intervention were inconsistent between parents and clinicians. For severity scores (CGIS), parents rated their children as more improved following HBOT (P = 0.005), while the clinicians found no significant differences (P = 0.10). On the other hand, for change scores (CGIC) the clinicians indicated greater improvement following HBOT (P = 0.03), but the parents found no such difference (P = 0.28).

CONCLUSIONS:
Children with autism who received 20 sessions of either HBOT or a sham air exposure had significant improvements in overall behaviour but there were no significant differences in improvement between groups. The inconsistent changes on CGI sub-scores between parents and clinicians are difficult to interpret, but no overall clinically significant benefit from HBOT could be shown. Both interventions were safe and well tolerated with minimal side effect from middle ear barotraumas.

Repeat for emphasis: “Children with autism who received 20 sessions of either HBOT or a sham air exposure had significant improvements in overall behaviour but there were no significant differences in improvement between groups”

Reports from parents and clinicians did not agree and the authors conclude “no overall clinically significant benefit from HBOT could be shown”.

HBOT is not cheap. A single “dive” can cost in the neighborhood of $100. Parents have purchased portable chambers which run in the $10-20k range (depending on model and whether new). And have modified these to provide O2 enriched air, outside the manufacturer’s specifications. There is a resale value in these chambers so far, so the net cost is not going to be as high. But, all told, there is substantial outlay of funds and time in HBOT. The science pro is shaky at best. And now there are two negative controlled trials.

These results will likely do little to dampen the enthusiasm for HBOT. All studies of HBOT and autism in clinicaltrials.gov are completed, so future data may not be forthcoming.

—
By Matt Carey

Chronic Intranasal Oxytocin Causes Long-Term Impairments in Partner Preference Formation in Male Prairie Voles

21 Oct

There is a great deal of discussion here and elsewhere about alternative medicine and it’s application to autism. If one points out that a specific therapy is poorly founded in facts and/or not completely tested, a common response is that one is “anti-cure” “anti-treatment” or the like. Safety issues, always at the forefront to the point of misrepresentation when discussion of vaccines, are often completely ignored in the alt-med world when discussing proposed therapies.

One therapy that hasn’t been discussed much here at LBRB is oxytocin. Some of the studies on oxytocin and autism have been, well, odd. But others have covered those aspects better than I could. Now comes a study on lab animals exploring long-term effects:

Chronic Intranasal Oxytocin Causes Long-Term Impairments in Partner Preference Formation in Male Prairie Voles.

Here is the abstract:

BACKGROUND: Oxytocin (OT) is a hormone shown to be involved in social bonding in animal models. Intranasal OT is currently in clinical trials for use in disorders such as autism and schizophrenia. We examined long-term effects of intranasal OT given developmentally in the prairie vole (Microtus ochrogaster), a socially monogamous rodent, often used as an animal model to screen drugs that have therapeutic potential for social disorders.

METHODS: We treated voles with one of three dosages of intranasal OT, or saline, from day 21 (weaning) through day 42 (sexual maturity). We examined both social behavior immediately following administration, as well as long-term changes in social and anxiety behavior after treatment ceased. Group sizes varied from 8 to 15 voles (n = 89 voles total).

RESULTS: Treatment with OT resulted in acute increases in social behavior in male voles with familiar partners, as seen in humans. However, long-term developmental treatment with low doses of intranasal OT resulted in a deficit in partner preference behavior (a reduction of contact with a familiar opposite-sex partner, used to index pair-bond formation) by male voles.

CONCLUSIONS: Long-term developmental treatment with OT may show results different to those predicted by short-term studies, as well as significant sex differences and dosage effects. Further animal study is crucial to determining safe and effective strategies for use of chronic intranasal OT, especially during development.

Basically they exposed prairie voles to oxytocin from about the equivalent of being a toddler (weaning) to adulthood (sexual maturity). It’s a short time for these animals (21 days) but in that amount of time the males showed changes in behavior beyond those observed in short-term trials.

This isn’t a complete “put the brakes on this line of research” study, but it does shed light on the sort of caution that should (and, sadly, often isn’t) applied to alt-med. Some have jumped the gun on oxytocin as a therapy before dosage and long-term effects have been explored.

Immunization uptake in younger siblings of children with autism spectrum disorder

12 Oct

If one child has autism, the chance that a younger sibling will have autism is about 18.7%. (see the study Recurrence Risk for Autism Spectrum Disorders: A Baby Siblings Research Consortium Study and discussions here and elsewhere). Anecdotally, we hear a lot about families deciding to forgo or delay vaccines after having an autistic child. This raises a question and an opportunity for research: does delaying or stopping vaccines result in a lower risk of autism? Looking at younger siblings, one would have a population that both has a higher autism risk and a possibly higher percentage of use of alternate (including no) vaccine schedule.

A study has been published this week on this very topic: Immunization uptake in younger siblings of children with autism spectrum disorder. The answer? Immunization does not increase the risk of autism. But I get ahead of myself.

The authors divided the children into three groups

Immunization status was divided into three predefined categories: (a) Fully immunized: Children with four doses of DPTP (2, 4, 6, and 18 months) and the initial MMR dose at 12 months, (b) Partial/delayed immunizations: Children with any missing dose of DPTP or MMR at any age or a delay of 3 months or more for at least one of the doses of DPTP or MMR, and (c) Not immunized/declined: Children for whom all immunizations had been withheld as of 3 years of age.

In case you are wondering, yes, comparing groups (a) and (c) is a vaccinated/unvaccinated study design. [edit to add–see note below] (b) just gives more dimension to the study.

Yes, siblings of autistic children are vaccinated differently (on average) than younger siblings of non-autistic children:

MMR immunization uptake. The analysis revealed a significant group difference in MMR immunization status (Fisher’s exact test = 80.82, p < .001). Bearing in mind that the Public Health Agency of Canada recommends that children receive their initial MMR vaccine at 12 months (in contrast to the United States, where it is recommended at 12–15 months; Public Health Agency of Canada, 2006a; CDC, 2011), only 42 of the 98 (43%) younger sibs received the 12-month MMR vaccine ontime (i.e. by at least 15 months of age; see Figure 2); an additional 38 (39%) received the vaccine after 15 months of age, and 18 (18%) had not been immunized against MMR by the age of 3 years. In contrast, 88 of 98 (90%) probands received the MMR by 15 months, 9 (9.2%) were delayed, and only 1 had not been immunized by the age of 3 years. Similarly, 63 of 65 (97%) controls had completed their MMR immunization on time (i.e. only two were delayed, and none had parents who had fully declined).

Only 42% of younger siblings of autistics received the MMR ontime. 18% were not given the vaccine by age 3. Compare this to the control group, where 90% received the MMR by 15 months and 98% by age 3.

Differences were seen with the DPTP vaccine as well:

DPTP immunization uptake. A significant group difference was also found for DPTP immunization status (Fisher’s exact test = 38.95, p < .001), with just over half (55.1%) of the younger sibs having been immunized on time (31.6% were delayed, and 13.3% were not immunized by the age of 3 years; see Figure 3). The rates of DPTP uptake were higher for probands (86.7% immunized on time, 12.2% delayed, and 1% not immunized) and controls (90.8% immunized on time, 9.2% delayed, and none declined).

What did this do to autism risk for these un- and under-vaccinated younger siblings? Statistically nothing:

Of the 39 younger sibs who had completed their immunizations on time, 6 (15.7%) were diagnosed with ASD and 2 with speech-language delay (SLD). Of the 47 younger sibs for whom immunization as delayed, 15 (31.2%) received an ASD diagnosis and 2 had SLD. Of the 12 younger sibs who had not received any immunizations, 4 (33.3%) were diagnosed with ASD and 1 with SLD. Note that of those children who did not receive a diagnosis, 43.8% were fully immunized. The Fisher’s exact tests revealed no significant difference in the rates of diagnoses between immunized and nonimmunized groups for MMR (Fisher’s exact test = 5.46, p = .22), DPTP (Fisher’s exact test = 3.65, p = .44), or both (Fisher’s exact test = 4.13, p = .37), although small sample size renders these comparisons exploratory only.

And, by “statistically nothing”, I am not saying, “the calculated risk for vaccinated siblings are higher, but we can’t claim they are because the p values aren’t statistically significant”. No, I’m saying, “the calculated values are lower for vaccinated siblings.”

The authors found about 15.7% autism risk for baby siblings. Very close to the Baby Siblings study mentioned above which found 18.7% risk. The risk found for siblings with delayed vaccination was 31.2% and for unvaccinated was 33.3%. Again, these values are not statistically significant from the 15.7%.

So, when one does a vaccinated/unvaccinated study, one finds that autism risk (for familial autism) is not increased.

Since people will undoubtedly be looking for the conflicts of interests for the study authors, the COI statement is “The authors declare that there is no conflict of interest.” and their funding is “This research was funded by the Canadian Institutes of Health Research and Autism Speaks.”

Limitations include sample size and the fact that the authors relied upon parent recall for much of the data:

Parents of 22.2% (58/261) of the children provided a copy of their child’s immunization record or had it sent by their doctor; for the remaining 77.8%, status report was based on parent recall (note that this information was typically gathered at each visit, at 3- to 6-month intervals, to avoid recall bias). Due to the potential for recall bias (e.g. see Dorell et al., 2011, for bias in recall for the older children), we examined the influence of information source (card copy vs parent recall) on immunization status. No significant relationship was found for MMR (Fisher’s exact test = .38, p = .84), DPTP (Fisher’s exact test =1.71, p = .44), or “both” (Fisher’s exact test = 1.58, p = .48).

Here is the abstract:

Background: Parental concerns persist that immunization increases the risk of autism spectrum disorder, resulting in the potential for reduced uptake by parents of younger siblings of children with autism spectrum disorder (“younger sibs”).

Objective: To compare immunization uptake by parents for their younger child relative to their
older child with autism spectrum disorder (“proband”) and controls.

Design: Immunization status was obtained for 98 “younger sibs,” 98 “probands,” and 65 controls.

Results: A significant group difference emerged for overall immunization status (Fisher’s exact test = 62.70, p < .001). One or more immunizations in 59/98 younger sibs were delayed (47/98; 48%) or declined (12/98; 12.2%); immunizations were delayed in 16/98 probands (16.3%) and declined in only one. All controls were fully immunized, with only 6 (9.2%) delayed. Within the “younger sibs” group, 25/98 received an autism spectrum disorder diagnosis; 7 of whom (28%) were fully immunized. The rates of autism spectrum disorder diagnosis did not differ between immunized and nonimmunized younger sib groups, although small sample size limits interpretability of this result.

Conclusion: Parents who already have one child with autism spectrum disorder may delay or
decline immunization for their younger children, potentially placing them at increased risk of
preventable infectious diseases.

Edit to add: The authors have clarified that unvaccinated means not vaccinated with MMR or DPTP, not necessarily completely unvaccinated.

The Nobel Prize in Physiology or Medicine 2012: for the discovery that mature cells can be reprogrammed to become pluripotent

9 Oct

The Nobel committee announced today that “The 2012 Nobel Prize in Physiology or Medicine was awarded jointly to John B. Gurdon and Shinya Yamanaka “for the discovery that mature cells can be reprogrammed to become pluripotent”.” The discoveries are discussed below. The short version is that Gordon and Yamanaka separately discovered that specialized cells can be changed into unspecialized cells.

Yamanaka was able to take mature cells and turn them into stem cells. This has opened up a large area of research including research in Autism.

Here is the press release:

The Nobel Prize recognizes two scientists who discovered that mature, specialised cells can be reprogrammed to become immature cells capable of developing into all tissues of the body. Their findings have revolutionised our understanding of how cells and organisms develop.

John B. Gurdon discovered in 1962 that the specialisation of cells is reversible. In a classic experiment, he replaced the immature cell nucleus in an egg cell of a frog with the nucleus from a mature intestinal cell. This modified egg cell developed into a normal tadpole. The DNA of the mature cell still had all the information needed to develop all cells in the frog.

Shinya Yamanaka discovered more than 40 years later, in 2006, how intact mature cells in mice could be reprogrammed to become immature stem cells. Surprisingly, by introducing only a few genes, he could reprogram mature cells to become pluripotent stem cells, i.e. immature cells that are able to develop into all types of cells in the body.

These groundbreaking discoveries have completely changed our view of the development and cellular specialisation. We now understand that the mature cell does not have to be confined forever to its specialised state. Textbooks have been rewritten and new research fields have been established. By reprogramming human cells, scientists have created new opportunities to study diseases and develop methods for diagnosis and therapy.

Life – a journey towards increasing specialisation
All of us developed from fertilized egg cells. During the first days after conception, the embryo consists of immature cells, each of which is capable of developing into all the cell types that form the adult organism. Such cells are called pluripotent stem cells. With further development of the embryo, these cells give rise to nerve cells, muscle cells, liver cells and all other cell types – each of them specialised to carry out a specific task in the adult body. This journey from immature to specialised cell was previously considered to be unidirectional. It was thought that the cell changes in such a way during maturation that it would no longer be possible for it to return to an immature, pluripotent stage.

Frogs jump backwards in development
John B. Gurdon challenged the dogma that the specialised cell is irreversibly committed to its fate. He hypothesised that its genome might still contain all the information needed to drive its development into all the different cell types of an organism. In 1962, he tested this hypothesis by replacing the cell nucleus of a frog’s egg cell with a nucleus from a mature, specialised cell derived from the intestine of a tadpole. The egg developed into a fully functional, cloned tadpole and subsequent repeats of the experiment yielded adult frogs. The nucleus of the mature cell had not lost its capacity to drive development to a fully functional organism.

Gurdon’s landmark discovery was initially met with scepticism but became accepted when it had been confirmed by other scientists. It initiated intense research and the technique was further developed, leading eventually to the cloning of mammals. Gurdon’s research taught us that the nucleus of a mature, specialized cell can be returned to an immature, pluripotent state. But his experiment involved the removal of cell nuclei with pipettes followed by their introduction into other cells. Would it ever be possible to turn an intact cell back into a pluripotent stem cell?

A roundtrip journey – mature cells return to a stem cell state
Shinya Yamanaka was able to answer this question in a scientific breakthrough more than 40 years after Gurdon´s discovery. His research concerned embryonal stem cells, i.e. pluripotent stem cells that are isolated from the embryo and cultured in the laboratory. Such stem cells were initially isolated from mice by Martin Evans (Nobel Prize 2007) and Yamanaka tried to find the genes that kept them immature. When several of these genes had been identified, he tested whether any of them could reprogram mature cells to become pluripotent stem cells.

Yamanaka and his co-workers introduced these genes, in different combinations, into mature cells from connective tissue, fibroblasts, and examined the results under the microscope. They finally found a combination that worked, and the recipe was surprisingly simple. By introducing four genes together, they could reprogram their fibroblasts into immature stem cells!

The resulting induced pluripotent stem cells (iPS cells) could develop into mature cell types such as fibroblasts, nerve cells and gut cells. The discovery that intact, mature cells could be reprogrammed into pluripotent stem cells was published in 2006 and was immediately considered a major breakthrough.

From surprising discovery to medical use
The discoveries of Gurdon and Yamanaka have shown that specialised cells can turn back the developmental clock under certain circumstances. Although their genome undergoes modifications during development, these modifications are not irreversible. We have obtained a new view of the development of cells and organisms.

Research during recent years has shown that iPS cells can give rise to all the different cell types of the body. These discoveries have also provided new tools for scientists around the world and led to remarkable progress in many areas of medicine. iPS cells can also be prepared from human cells.

For instance, skin cells can be obtained from patients with various diseases, reprogrammed, and examined in the laboratory to determine how they differ from cells of healthy individuals. Such cells constitute invaluable tools for understanding disease mechanisms and so provide new opportunities to develop medical therapies.

Sir John B. Gurdon was born in 1933 in Dippenhall, UK. He received his Doctorate from the University of Oxford in 1960 and was a postdoctoral fellow at California Institute of Technology. He joined Cambridge University, UK, in 1972 and has served as Professor of Cell Biology and Master of Magdalene College. Gurdon is currently at the Gurdon Institute in Cambridge.

Shinya Yamanaka was born in Osaka, Japan in 1962. He obtained his MD in 1987 at Kobe University and trained as an orthopaedic surgeon before switching to basic research. Yamanaka received his PhD at Osaka City University in 1993, after which he worked at the Gladstone Institute in San Francisco and Nara Institute of Science and Technology in Japan. Yamanaka is currently Professor at Kyoto University and also affiliated with the Gladstone Institute.

Key publications:
Gurdon, J.B. (1962). The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. Journal of Embryology and Experimental Morphology 10:622-640.

Takahashi, K., Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663-676.

KQED in San Francisco has a good story and interview on the award in SF Scientist Wins Nobel for Stem Cell Breakthrough. Here’s the beginning of that story:

Shinya Yamanaka, a stem cell researcher at the Gladstone Institutes, which is affiliated with the University of California, San Francisco, has won this year’s Nobel Prize in Physiology or Medicine jointly with English researcher John B. Gurdon.

Here is the video from that story (I can’t get the video from the Nobel site to embed):

One great example of the application of this work is in autism research. A topic of much discussion recently was the work of Ricardo Dolmetsch (who, to be clear, did not share this award) of Stanford who has been taking mature skin cells from autistics, reverted them to pluripotent stem cells and, from these, grown cells of other organs like the brain or the heart. By studying these cells, they are learning about the differences in brains of autistics.

—
By Matt Carey

Mark and David Geier, holed up in Missouri?

5 Oct

There is really no fun in writing about people whose lack of ethical standards harm disabled children. Seriously, it is painful. I know at least one autism blogger who quit in no small part because it was just too hard to keep writing about these topics.

And here in one week, both Andrew Wakefield and the Geiers (Mark and David) come back up in the news. A recent story in the St. Louis Post Dispatch discusses the Geiers: Controversial autism doctor loses license elsewhere, but can still practice in Missouri, Illinois

Mark Geier is an M.D. and was licensed in multiple states (I’ve lost count of how many and which ones). His home base is Maryland. His license was suspended there and many other states have followed suit. David Geier holds no medical credentials and is charged with practicing medicine without a license in Maryland.

As noted above, most, but not all, states have followed suit with suspending Mark Geier’s license.

The St. Louis Post Dispatch writes (reminding me of which states Mr. Geier has been licensed):

Dr. Mark Geier has opened eight autism treatment clinics called ASD Centers across the country but is only allowed to practice at two of them — in St. Peters and Springfield, Ill.

Missouri and Illinois are among the last states to seek discipline against Geier, whose hormone therapy for children with autism has been called dangerous, abusive and exploitive by various medical boards.

In the last two years, his medical license has been revoked or suspended in California, Florida, Indiana, Kentucky, Maryland, New Jersey, Texas, Virginia and Washington.

Missouri, Illinois and Hawaii have filed complaints against Geier based on other states’ actions, but his license remains active in all three states. A disciplinary hearing in Geier’s case is set for Oct. 19 before the Missouri Board of Registration for the Healing Arts in Jefferson City

The Geier hypothesis is that mercury binds with testosterone in the brain, making it difficult to chelate. They prescribe Lupron to reduce testosterone. The idea would be laughable if it weren’t being used on humans (or any animal for that matter).

Briefly–the Geier’s cited a paper showing that in hot benzene,
(more details in Miscellaneous Mercury Nonsense), mercuric chloride and testosterone can be induced to form chemical complexes.

I had hopes that the Geiers had moved away from this idea, but they stand by it:

David Geier said Wednesday that “many peer-reviewed scientific studies” have been published that support the theory. All of the research articles cited on the ASD Centers’ website are co-authored by Mark or David Geier.

The fact that the Geiers were able to get papers published in third rate journals doesn’t make their ideas true. Or even feasible.

Mr. David Geier did not attend medical school. Neither did I but I will offer him this small bit of medical advice: Among other logical problems with your idea, the human brain is not the same thing as a beaker of hot benzene.

Point two: even if your idea held any merit, Lupron lowers the level of testosterone in the blood, it doesn’t break up these mythical mercury-testosterone complexes.

The Geiers are demonstrating a major problem with the medical license system in the U.S.. It took years to bring the Geiers to hearing. Now that Mark Geier has lost his license in his home state, he has moved to other “safe havens” to continue business? How is this right.

I recall a number of med students and premeds I knew while in college and grad school. The hoops they had to jump through to get their degrees and get licensed and start working seemed enormous. Now we see why: it’s so hard to stop someone from practicing.

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