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Don’t just glance at the title and then ask, “Is he off his rocker?”  “What’s in the water cooler at Atlanta Hyperbaric?”  No, I said oxytocin, not OxyContin®.  The first is a hormone, sold under the trade name of Pitocin®, and the second is an opioid pain killer with a habit-forming potential. It’s an easy mistake to make, unless you happen to be a pharmacist or are otherwise familiar with these drugs.

Oxytocin was first isolated in 1953 and has been available to physicians at least since I was a medical student in the 1960’s. Oxytocin is commonly used by obstetricians (as a  ”pit drip”)  in the induction and management of labor and delivery.  Of course, just because a drug is old and familiar, doesn’t make it good, bad, safe or dangerous.  But, old drugs are relatively well studied and predictable, so it is always welcome news when researchers start looking at new indications for an old drug.

Oxytocin has profound and complex behavioral effects, largely documented in animals, but increasingly observed in people.  In humans, oxytocin induces trust, increases generosity, but also  stimulates envy and gloating.  Oxytocin has even been called the love hormone.  Autism is characterized by three symptom categories: speech and communication abnormalities, social functioning impairments and repetitive behaviors and restricted interests. Plasma oxytocin levels have been reported to be abnormally low in autistic patients, so it is not surprising that this powerful drug is also being tried as an autism treatment.

This week a group of French researchers reported that oxytocin improved the abilities of autistic adults to interact with other people.  The researchers had the patients play a video ball-tossing game, in which the patients threw balls to cartoon characters with three different behavioral profiles:  One player always returned the ball to the patient, another player never returned the ball, and the third player indiscriminately returned the ball to the patient or to other players.  Before oxytocin, the patients threw the ball randomly to all three players, but after oxytocin, the patients preferred to throw to the guy who threw it back to them.

The scientists also measured the patients’ attentiveness to social signals.   Patients looked at photos of faces on a computer and were asked to identify either the gender or whether the face was looking into the camera or away to one side. The focus of participants’ gaze was recorded. Mean time spent looking at the faces, as opposed to elsewhere, was about 20% to 30% greater following oxytocin treatment both in the gender identification and the facial-direction tasks.  The patients also would sometimes look directly at the eyes in the photos, which they never did without oxytocin.

At baseline, mean plasma oxytocin levels were 1.08 pg/mL in patients compared with 7.28 pg/mL in the healthy controls (P<0.0001). Ten minutes after intranasal oxytocin in the patients, their plasma levels were still only 2.66 pg/mL, yet despite the persistent shortfall in plasma oxytocin and substantial individual variability in performance, the lead investigator said, “We demonstrated that oxytocin can promote social approach and social comprehension in patients with autism.”

This study is great stuff.  Of course, it only looked at a few adult patients and researcher biases could have poisoned the well.  But I am encouraged and time will tell whether oxytocin replacement therapy can help autistic patients, children and adults, over the long run.

Another week in the books at Atlanta Hyperbaric and two interesting things happened: First, an article came out on maternal age and autism and second, a patient was referred with chronic Lyme disease.  We, of course, treat autism and keep an open mind about Lyme disease.

The autism study should be much admired by epidemiologists.  The study group comprised nearly 5 million births in California between 1990 and 1999 and more than 12,000 autism cases.  With such large numbers–assuming they are reasonably accurate–the findings should be pretty reliable. Mothers who gave birth when they were 40 or older had a 51% increased risk of having a child with autism compared with those who were 25 to 29, the largest age group.  Paternal age effected autism rates only if mothers were younger than 30.  Maternal age, however, accounted for just 4.6% of the autism incidence while over the same time frame, overall autism incidence increased by a factor of 6.  In other words, according to the authors, rising maternal age definitely seems to contribute to the increase of autism cases, i.e., is a risk factor for autism, but only accounts for a fairly small proportion of all the increased number of autism cases being seen.

Chronic Lyme disease is about as controversial a topic as there gets in Medicine.   Dr. Allen C. Steere, the discoverer of Lyme disease, reported death threats in 2001 because he took a very public position that people diagnosed with chronic Lyme disease generally don’t need to be treated with more than a month of antibiotics; because of his stature and reputation, many insurers stopped paying for the antibiotic treatments and State regulatory authorities started going after physicians writing the prescriptions.  Dr. Steere’s position in July 2008 on chronic Lyme disease appears unchanged.

Regular readers of this blog have probably figured out by now that I am a libertarian.  For the uninitiated, my definition of a libertarian is basically someone who believes that all problems on Earth are caused by government.  All problems.  Even dog fleas (see page 7.)  If a patient wants IV antibiotics for chronic Lyme and a physician wants to prescribe them, I don’t see why the government needs to stick its metaphorical nose into the issue.  I may not believe the antibiotics will have any beneficial effect and, indeed, I suspect chronic antibiotics have harmful effects under these circumstances, but I won’t condemn either the physician or his patient.  To me, the marketplace solves this problem better than any bureaucrat and I believe the market never errs, if allowed to be free.  And, please don’t bring up the wastefulness argument because that spills over into another topic entirely and has nothing to do with whether a doctor should be allowed to prescribe antibiotics when the State says he shouldn’t.

If you think that treatment of chronic Lyme disease with antibiotics is controversial, you can imagine the literature on hyperbaric oxygen treatment for this condition.  At least there have been no death threats: It is uncommon for insurance companies to pay in the first place and no one proposes–yet–to interfere with this doctor-patient relationship.

Over the years, I have treated with hyperbaric oxygen about half a dozen patients who carried the diagnosis of chronic Lyme disease.  These patients all had positive blood tests for Lyme, several had documented erythema chronicum migrans, all had multiple courses of both intravenous and oral antibiotics and all continued to have long standing complaints of severe fatigue, sleep disturbance, headaches or cognitive problems.  In other words, all of these patients had acute Lyme disease at one point in their lives and then developed chronic, nonspecific symptoms.  Everyone of these patients has sworn to me that the hyperbaric oxygen treatment helped their symptoms.

Is there any scientific evidence that hyperbaric oxygen helps patients with chronic Lyme disease? I am only aware of one study, and the only thing I can make of it is that hyperbaric oxygen harmed no one–rarely does it ever–and more than 80% of the patients claimed their symptoms improved.  There is at least a scientific rationale behind the use of hyperbaric oxygen treatment: The spirochete that causes Lyme disease is sensitive to a high-oxygen environment.   Under hyperbaric conditions, there can be no place in the human body for the Lyme spirochete to hide from oxygen levels that should be able to kill it.  Let’s see how my new patient does.

Earlier this week, The Lancet, the prestigious British medical journal, published the following short retraction:

It doesn’t get any more serious in the world of science.  Ordinarily,  a scientist who realizes an error in one of his published papers simply stops referring to the report and allows it to die an unceremonious death.    Occasionally, a scientist of especial probity will voluntarily publish a retraction and explanation.  But, it is distinctly unusual for someone to be accused of scientific fraud, much less twelve years later.    What usually follows is a series of denials and recriminations, finger pointing and objurgation, though mostly in-house, because science usually affects only scientists.  The big controversies that spill over to the general public–and this one is the biggest in years–typically leads to great fonts of oratory from people who don’t know much about science,  but who do hold the reins of power.  Heaven forfend, we will not see any of our wise Solons in Washington pass new laws or regulations to protect us from future trespasses.

Of course, we treat autistic kids at Atlanta Hyperbaric.  And, they are very dear to me.  As I’ve said many times before, I would love to have a practice that ONLY treats children, for the selfish reason that it makes me feel good to help out kids who will be around long after I’m gone.  Consequently, this English dust up hits pretty close to home.

Few minds will be changed by The Lancet retraction.  Even though mainstream medicine subsequently brought forward a large volume of research casting doubt on any association between vaccines containing mercury preservatives and autism, The Lancet report did much to propel the controversy.  People took sides and, depending on their view of the dispute, kids paid the price either by going unvaccinated and risking mumps, measles and rubella or by getting vaccinated and risking autism.   The great gods of government stepped in and took Thimerosal, the main mercury-based preservative in the United States, off the market.   Litigation has raged, including a recent plaintiffs’ decision by the Georgia Supreme Court. [American Home Products v. Ferrari, 284 Ga. 384, 668 S.E.2d 236 (2008.)]  I suspect that hundreds of millions (more?) of dollars have been spent on this controversy.

What can we learn from this mess?  We already knew that scientists were human and subject to the same character flaws as everyone else.  We also knew what side the weight of scientific evidence fell in this particular instance.  So I guess we really don’t learn anything.  More scandals will occur, more pundits will opine, more people will be injured and more money wasted.  And, God help us, more politicians will solve our problems.

Atlanta Hyperbaric treats children with autism so we like to report about new studies of this disorder.  It has long been suspected that perinatal exposure to a toxin is involved.  Thimerosol in childhood vaccines, for example, has received widespread attention as a possible causative factor.

Researchers reported a statistical study in California recently to determine whether geographical clusters of autism exist and, if so, whether any environmental associations were present.  Using birth records to find the mother’s address, the authors linked up data on 9,900 autism cases recorded in the California Department of Developmental Services (DDS) database.  The authors made the reasonable assumption that the address of the birth mother would reflect the baby’s perinatal environment.   To be considered an autism cluster, the area had to have at least 70% greater risk than surrounding areas in seven different tests for clustering; they authors found 10 of these clusters throughout the state.  The authors, however, found no ready explanation for the clusters.

I thought these authors had a pretty good idea to work with and perhaps they will be able to  mine  their database further.  They had to start somewhere and if they can find some useful statistical associations, they might ultimately help identify a risk factor that could be modified to allow us to reduce the risk of autism.

This year saw the publication of the most important study of autism and hyperbaric oxygen therapy in my memory, namely, Dr. Rossignol’s double-blind study, which reported that the patients treated with hyperbaric oxygen showed decisive improvements in language, social interactions and other measurable areas compared to the controls.  His study results reinforced my clinical experience treating autistic kids with hyperbaric oxygen at Atlanta Hyperbaric. About two months ago, I blogged about a government study reporting an increased rate of autism based on a survey of parents.  Now the Centers for Disease Control, my former employer, have reported confirmation of this increase of autistic kids.

CDC’s Autism and Developmental Disorders Monitoring (ADDM) Network reported from 11 sites in the U.S. that autism spectrum disorder prevalence in 2006 ranged from about one out of 80 children to one out of every 240 children, with an overall prevalence of one in 111 youngsters.  This overall estimate is slightly lower than that from a study using data from the 2007 National Survey of Children’s Health — one in every 91 children — that I blogged about in October.  Ten of the ADDM sites reported data from both 2002 and 2006, showing an average 57% increase in ASD prevalence. So, looking at both studies together, roughly one percent of all children have autism and the rates are getting higher.

According to the authors, some of the increased rate of autism is likely due to better detection, particularly among children who may not have come to attention in the past, including girls, Hispanic children, and children without cognitive impairment, however, a simple explanation is not apparent and a true increase in risk cannot be ruled out.  The authors were also cautious to report the limitations of their study.

We are in a highly charged political environment for health care, so it was not surprising that a prominent autism advocacy group wants to lay the economic responsibility of autism on the government.  “Now that the government has confirmed that one percent of American children have autism, the question becomes what it will take to get our elected leaders to wake up and take on this crisis in an appropriate way,” one of the group’s founders said.

Here we go again.  Now, if the government were to fund hyperbaric oxygen therapy for autistic kids, Atlanta Hyperbaric could make a lot of money, and I would be foolish to turn the business away.  But, I do not see the justification of using the coercive police powers of government to take even more money from the beleaguered taxpayer in order to benefit these seriously challenged kids.  Think about it for a minute.  You work hard to meet your family’s needs. You  may have a child  who shows a lot of potential and perhaps you would like to send him to a private school where he will enjoy smaller class sizes and superior facilities.   You scrimp and save and maybe work a second job so you can afford the tuition.   Then government comes around and takes some of your “extra” money in order to give it to one of your neighbors who have an autistic kid so that he can get hyperbaric oxygen therapy.  You now may have to work even harder to send your child to private school–or abandon your hope altogether.  Here is Ronald Reagan in 1961, with Medicare on the horizon, speaking out about the chilling loss of freedom that socialized medicine would cause.  Too bad we didn’t listen to him.

New information seems to be coming out daily about autism and Atlanta Hyperbaric has seen more referrals for hyperbaric oxygen treatment of autistic children this year than previously.  As a matter of fact, there may be more autistic children around than previously thought.  A new government study of parent-reported cases of autism, claimed higher rates than previous studies. Based on a survey performed in 2007, this study found an autism rate of 110 per 10,000, or about 637,000 in the United States overall.  Boys had autism rates about 4 times that of girls.  Perhaps most interesting is that some children might possibly outgrow the disease.  Almost 2 out of 5 of these children had been given a diagnosis of autism at some point in their lives, but currently were not believed to have autism.  The authors cautiously pointed out the diagnosis of autism is less precise in the youngest children, so that some of the children diagnosed at a younger age simply never had  autism and this fact became more obvious as the child grew up.  On the other hand, many pediatricians who have been following patients for long periods believe that some autistic children do recover.

Most psychiatrists prefer to call the newer antipsychotic medications “atypical antipsychotics” rather than “second-generation antipsychotics.”   Perhaps that’s because the first one, clozapine (Clozaril®), was discovered in the 1950’s.  In any case, resperidone (Risperdal ®,) which was first marketed in the United States during the 1990’s, is approved by the FDA for treatment of irritability in autistic children.  At the American Academy of Neurology meeting this Spring, researchers reported that another atypical antipsychotic, aripiprazole (Abilify®), was significantly better than placebo for irritability and hyperactivity in autistic children.  Although use of Abilify® for this indication is off label, pediatricians will have an alternative to Risperdal® to consider.

I will be posting commentary on different aspects of hyperbaric medicine, especially about the use of hyperbaric oxygen to treat neurologic injury and disease. But, any medical issue I find interesting in hyperbaric medicine will probably find its way into this space, sooner or later. Whether you live here in the Atlanta area or elsewhere, please feel free to post questions, comments or other remarks. I will do my best to answer questions and, if I don’t know the answer, I’ll try to find someone who does. I started Atlanta Hyperbaric in 1987, so I have a lot of clinical experience in hyperbaric medicine to draw on. I hope we’ll get some good discussions going and learn something at the same time.

I want to start out taking a look at a recent study on the use of hyperbaric oxygen to treat patients with autism. Dr. Rossignol and his associates in Melbourne, Florida collected 62 patients with autism into a randomized, controlled, double blind trial to see if hyperbaric oxygen is of benefit to these kids. The treatment protocol Dr. Rossignol chose was a little different than what we customarily use at Atlanta Hyperbaric to treat our brain injury patients—we use the protocol that the late Dr. Richard Neubauer, the great pioneer of hyperbaric oxygen treatment for brain injuries, developed—however, I think that Dr. Rossignol’s conclusions are applicable to our patients at Atlanta Hyperbaric.

Immediately after completing 40 one-hour hyperbaric treatments delivered over a four-week time frame, the hyperbaric oxygen treatment group showed statistical improvements in a variety of clinical areas compared to the control group, including measures of irritability, hyperactivity, speech and cognitive awareness.

What does Dr. Rossignol’s study prove? Although it is easy to carp at the relatively small number of patients, the lack of follow up and the placebo response, it is not so easy to dismiss the statistically significant differences between the hyperbaric oxygen treatment and placebo groups. Besides, other available double-blind studies in autism treatment suffer from the identical kinds of problems as Dr. Rossignol’s–this study is at least as well designed as any other in autism that I have seen. It is extremely difficult or maybe even impossible to fund and conduct an ideal double-blind study in autism.

Hyperbaric oxygen is a treatment known to improve brain blood flow by stimulating the growth of new blood vessels into areas of reduced blood flow. Other researchers have shown with SPECT and PET scans that the bulk of autistic children have low blood flow in the areas of the brain believed to be responsible for the behavioral manifestations. Because conventional treatment of autism is supportive, rather than curative, I believe Dr. Rossignol’s study is important. And, the new blood vessels that hyperbaric oxygen stimulates are believed to be permanent, so the potential of hyperbaric oxygen is that it can permanently improve symptoms in autistic children. To me, that’s exciting.

Glenn L. Goodhart, M.D., J.D.