What's Up Doc?

Can you fix something without truly understanding it?

 

 

If you ask a brainy engineer, the type that designs jet engines or nuclear reactors, can you solve a problem without understanding it; the answer is likely to be negative.  If you ask the guy that fixes your car, he might say “dunno, but let’s have a go”.  I have never met a white coated medical researcher, so I cannot tell you how they would reply.

 

A long time ago I gave up on expecting experts to fix types of unusual problems.  Like the illuminated “engine malfunction” light that sometimes appears in my car, like why did the radiators in my house bang and clank as they warmed up and later as they cooled down (it's not air in the system).  Why did my environmentally friendly solar panels make a noise like they were about to explode? The list grows longer.  Having solved all these problems and some others, I moved on to healthcare.  Why did my chest hurt when I sneezed? very funny to watch, instead of my reflex being to cover my mouth, I would hold my chest.  Then I even started giving medical advice to my Mother, a doctor herself.  But I digress.

 

If somebody had asked me, prior to Christmas 2012, "so Peter can you fix Monty?" then the best I could have said would have been something dull like:-

  

Autism is an incurable condition that you can manage, but you cannot reverse or cure it pharmacologically. Maybe one day there will be a cure, but too late for us.  Using behavioural techniques Monty has made great strides forward.  He can walk, run, ski, swim, read, write, do basic addition and subtraction.  He has emerging understanding of Wh- questions.  When asked a specific question he may make a short verbal reply, or he might totally ignore the questioner and the question.  A lot depends on who asks the question.  He sometimes suffers from stereotpy (aka stimming) particularly at school and this can makes it hard to complete simple academic work.  He may sometimes disrupt the class, even though he has a 1:1 assistant.  When his brother, Ted, asked if Monty will ever learn to drive I answered “maybe, maybe not, let’s hope for the best”

 

 

 

Three months later, and two months after everybody now knows about the Bumetanide Epiphany, my wife says to me out of the blue “Do you think you can really fix Monty” and even “What’s up, Doc”. Well, I never said I could or would fix him, but at least I am going to have a dam good try. Ted’s odds of getting Dad’s old Triumph Spitfire all to himself are slipping daily from odds-on favourite. If they slip to 50% my job will be complete.

 

 

So, can I fix something without truly understanding it?

Well, quite possibly, but the more I understand the problem, the better are my chances.

In neurobiology nobody fully understands the subject.  It is a work in progress. By the time Monty and Ted draw their pensions, it will still be a work in progress.

 

 

We speak your language - Ми говоримо ваш језик

I am pleased to  see that most people reading this blog are not native English speakers.

Dule ("Doolay", for those English speakers)  has very kindly offered to translate the useful parts of the blog for his friends into their language.  The nice people at Google have fortunately made that job a little easier, but as you can see below, they know some languages much better than others.
 
This blog has a translate feature.  Just look under the duck on the skateboard and you will see a Google Translate button.  (Sadly, the Google search this blog feature is not yet working)

           TRANSLATE

Select Language  

 Click the little down arrow and take your choice.

  

Ми говоримо ваш језик

Видим да већина људи читају овај блог нису Енглески матерњи језик.

Овај блог има за превод функцију. Само погледајте под патком на скејтборд и видећете Гоогле Транслате дугме.

         ТРАНСЛАТЕ

         Изаберите језик

Кликните на малу стрелицу надоле и да свој избор.

  

 

Акожелите да чујете нешто врло смешно, идите до главног Гоогле транслате вебстранице и кликните на малу слику говорника.Тада ћете добити аудиопревод. Звучи као кинески са веома лошимпрехладе.

 

 

Nous parlons votre langue

Je vois que la plupart des gens qui lisent ce blog ne sont pas de langue maternelle anglaise.

Ce blog a une fonction de traduction. Il suffit de regarder sous le canard sur la planche à roulettes et vous verrez un bouton Google Translate.

TRADUIRE

Sélectionnez la langue

Cliquez sur la petite flèche vers le bas et faites votre choix.

 

Google parle très bien français. Moi, je fais de mon mieux. Mais je peux apercevoir quelques erreurs. (traduit par Google)

 

 

 

 

私達はあなたの言語を話す



私はこのブログを読んで、ほとんどの人が英語のネイティブスピーカーではないことがわかります。

このブログは翻訳機能を持っています。ちょうどスケートボードのアヒルの下を見て、あなたはGoogle翻訳のボタンが表示されます。

TRANSLATE

言語を選択

少し下向き矢印をクリックし、あなたの選択を取る。

If you are looking for a clever comment in Japanese, dream on !

 

Nom de guerre, Mon frère - Manchopathy

Today’s post had better be a quick one.  The desk research in the background is getting complicated and I have just ordered a 900 page book on Human Physiology, so as not to spout complete nonsense.  Worse still, a couple of days ago, I received in the mail, a big brown envelope from Tokyo with a juicy report on the use of Ceredist, a TRH analog.  It is 20 pages long, and the bad news is that 18 pages are in Japanese.  The good news is that I had expected all 20 pages to be in Japanese.

To business.   You are slowly being introduced to the cast members of this blog.

The star of course is “Monty”, aged 9.

His supposedly “typical” big brother, aged 12, is going to be called “Ted”.

Head of Applied Research, part-time biker and Speech Therapist will be called Dule (“Doolay”)

Last week I decided that it was time for some good old fashioned primary research, to test a hypothesis that I had formulated.  This is what we presented to the in-house ethics committee, for approval:-

1.    Many children with autism exhibit what appears as sensory overload.  On hearing a moderately loud sound, they will cover their ears, almost as if in pain.  Bright lights, darkness, certain smells, even touch can trigger similarly strong reactions.  Entire books have been written documenting these odd behaviours, but I never read an explanation for them.

2.    In my trawl through the literature, I noted that a disorder with surprisingly similar symptoms has been documented -   Hypokalemic sensory overstimulation

This disorder manifests itself as an overwhelming feeling of sensory stimulation.  But then disappears 20 minutes after a dose of oral potassium.  A related, but much more severe, disorder that causes temporary paralysis also exists -  Hypokalemic periodic paralysis

3.    The recommended daily amount of potassium for adults is 3,500mg.  A typical banana contains 400 mg of potassium. A dissolvable tablet of Potassium Citrate contains 500mg of potassium.  So 500mg is a safe dose to experiment with.

4.    A laboratory experiment is proposed using an MP3 file of a baby crying. Dule will first establish a baseline volume (VB) at which Monty will cover his ears. Monty will be sitting in a fixed position in the lab. This test will be repeated over a few days to see if VB varies.

 

5.    Then the subject will receive 500mg of oral potassium and wait for 20 minutes. The MP3 file will be played again while he is sitting in the identical test position. Dule will crank up the volume and note the new threshold volume (VT).

 

6.    The same test will be repeated with Ted and Dule as subjects.

 

Prior to providing Dule with the oral potassium solution, Peter suggested to Dule that he would perhaps prefer if the test did not show up anything worthy of further investigation.  Since that would again drive Peter crazy, that no serious scientist had noticed this, done something about it and published their work.

Here is the raw data from the test:-

 

Volume * at which sound becomes disturbing
	7-Mar-13	8-Mar-13		11-Mar-13		11-Mar-13
						after K+
Monty	9	9		9		16
Ted				23		26
Dule				21		23
* sound level on digital display of Philips mini HiFi
room is about 20 m2, subjects were 2.5 m from HiFi unit

 

Discussion

As you see, Monty is far more sensitive to sound than both Ted and Dule.  Monty experiences a sharp increase in his capacity to cope with sound stimulation after drinking the potassium.  Ted and Dule show a small increase in capacity, that may be just down to measurement tolerance/error. (Dule was testing himself, after all)

Mon Dieu!  It looks like we have to do a serious follow on study with more subjects and some flashy equipment.  Worse still, now I have to be able to explain scientifically why this is happening !

 

The cause is related to something called VDCC (voltage dependent calcium channels) these are like little valves that open to let  Ca²⁺ ions in or out; they are misbehaving.   Recall that Bumetanide works in a similar way by triggering NKCC1 and NKCC2 (Sodium, Potassium, Chloride Cotransporters) to let in/out  Cl^- ions.  The subject of misbehaving ion channels has already been given a fancy name by scientists, its Channelopathy.  Now I was wondering how I was going to explain my use of French in this post.  It's all about the English Channel or should I say la Manche, and so we'll call it Manchopathy.

 

 

 

Beware of Men in White Coats - plus some interesting research

I am not quite ready yet to start presenting my own research findings.  They will start appearing in a few days.  In the meantime there are a couple of very readable papers from two different sources that are well worth looking at.

The first paper is a review of drug therapy in autism.  It was written in 20102 and includes more drugs than appear in comparable literature written in the US.  As a matter of interest, it was written by Indian scientists, but published by the Polish Academy of Science.  It is open access, so you can download it in full.

It is highly readable and even includes Bumetanide, my original epiphany drug.

Well done Baldeep Kumar et al from Chandigarh.  If it was up to me, all parents of kids with autism would get a copy of your paper Drug therapy in autism: a present and future perspective.  At least they would then have a sound factual understanding of what is available and what is on the horizon.

 

The second paper sounds even better:- Novel and emerging treatments for autism spectrum disorders: A systematic review.  It is also free to acces the complete paper.

It is published by the American Academy of Clinical Psychiatrists.  I have no idea who they are, but the name sounds very impressive.  The paper is certainly worth your time to read and undoubtedly took a great deal of desk research.

However, as I pointed out in my earlier post, about primary and secondary research you have to be very careful who is analysing the data.  It is best to do it yourself, whenever possible, or failing that contact Baldeep in Chandigarh.  Always read the label, even if you are one of those people that cut them off.  The paper is written by an author who is so prolific even my desk has got 5 of his papers lurking on it.  He is a big believer in the merits of hyperbaric oxygen therapy. The problem is I also have 2 papers on my desk that are highly critical of how he interprets his research data.  I think he may be suffering from Autistic Stress Syndrome (ASS) that I introduced in an earlier rather harsh post.

In her paper, Doreen Granpeesheh really lays into his powers of analysis and data interpretation.  Look at the bottom of page 272 if you are interested.

The other paper I have, really trashes the author.  Enough said.

Beware of Men in White Coats.

 

The risk of doing nothing

Everything you do entails some level of risk.  What is important is to understand the risk and takes steps, where necessary, to mitigate it.  We do this every day, even if we do not realise it.

 In the field of autism there are many risks to consider in daily life.  Many of them are the same risks that apply to very young typical children;  running out into the road without paying attention to the traffic, falling into an unattended swimming pool, even touching a hot iron, or hot pan on the cooker.  These are risks you can mitigate by good parenting.

When it comes to chemical/pharmacological interventions extreme care should be taken by the parents.  This puts them in an awkward question.  They undoubtedly want a miracle cure and thanks to the internet there is no difficulty in accessing them.  When such therapies are put forward by actual medical doctors, mainly from North America, you can hardly blame the parent for turning off their built-in risk assessor.  The doctor must know best.

I am not going to give you a list of the various chemicals/supplements/drugs that some parents are even injecting into their kids.

I think you need to do your own risk assessment of whatever intervention(s) you are going to use, be it behavioural, chemical, musical, swimming with dolphins etc.  If you are not able to assess the risk, then best not to take it.

If there is no downside, it is not going to be the end of the world if there turns out to be no benefit.  It may just lighten your wallet a little.

For me, the biggest issue has always been the risk of doing nothing.

 

My own experience with risk

I have taken some seemingly big risks in my time, but because I usually took mitigating action, I never came to regret them.  I travelled once from Delhi, up through floods in Nepal, across the Himalayas to Tibet, across to Hong Kong, then back to Beijing and across what was then Soviet Russia, to Moscow, then East Berlin over to the English Channel and home.  This was all done over land with public transport.  I came back without even a scratch, although several kilos lighter.

When you stop thinking about the risks, is when trouble will find you. A year after graduating from Imperial College, I heard that my favourite professor, Neil Watson, a world renowned expert on turbochargers (page 2 of link), had fallen off a ladder at home and killed himself.  Many years later, I nearly killed myself, on my own building site, falling backwards into an empty swimming pool.  

E Learning or is it E(asy) Learning !

This blog is mainly about finding science-based therapies for autism and the focus is actually on the pill-popping variety.  If you ended up on this blog looking for general tips to help for your recently diagnosed child with ASD, this is a post just for you.

Before getting to the easy part, let’s keep in mind the foundations on which it should be built.

 
Applied Behavioural Analysis (ABA)

If you know nothing factual about ABA (and there are lots of bizarre stories on the web and spread by followers of other faiths), you will be interested in a great new free resource on YouTube.  A company called Butterfly Effects published a superb series of free training videos.  I wish they had been around 5 years ago.  Here is one halfway through the course when the child is already partially verbal.

 

There are currently 66 videos in their channel, scroll down a bit to get to the nitty gritty.  They also do on-line training courses.

The other link is a web-based retailer in the US that ships worldwide all the books and accessories you could possible need for your home-based ABA programme.  They used to do a starter pack with what you need to get going.

Those two links should be enough to get a motivated parent into action.  If it does not, then ABA probably will not work wonders for you.  With ABA, you have to put in a great deal to get a little back, then slowly, investing a great deal starts to give you a lot back.

Now for the E(asy) Part

E  Learning

Going back to the not so distant past, when there was no internet and you did not have a computer at home, let alone in your jacket pocket, I learned some new acronyms:-  CAD (computer aided design) and CAM (computer aided manufacturing).  Nowadays most of us have a pretty good idea of what this is all about.  At the time I thought CAD-CAM was pretty cool.  That makes me an early adopter.  So no surprise then that I looked to see how computers could help with learning in autism.  Five years ago, there were no Ipads, but you could easily buy a touch screen monitor for your home PC. There are now lots of Apps written for kids with ASD and the good news is they are cheap.

I spent a small fortune on computer-based training (CBT) and its techy cousin Web-based training (WBT).  It was money well spent.  In reality the adult generally needs to sit by the PC, so it is better described as computer assisted learning (CAL).  Whatever you call it, it is great.

Toddlers learning to communicate

From about age 2 and up I would strongly recommend Laureate Learning

They have a special website for families, as opposed to schools and therapists, with lower pricing, but it is still seriously expensive.  The software logs the child's performance and only when one area is mastered can he move forward.  There are specific programmes for each topic, for example nouns, verbs, prepositions etc.

I spent many hours using the entry level programs with my son, before he was verbal.  They were really helpful and allowed him to show that he really did have a wide receptive vocabulary and understanding, even though he could not talk.  At that point (under 4 years old) we used a touch screen, rather than a mouse and it worked a treat.  He could very happily spend 20- 30 minutes per session.

If your budget cannot stretch to Laureate Learning, there is much cheaper alternative to see if your child is going to like computers. It is called LDA software, from Sherston.   It is not as sophisticated, but I still spent many hours prompting my son to use it.  LDA make a wide range of flash cards that form the initial basis of a home ABA programme, Sherston just made a computer programme out of the cards.

The software is a bit old (2005)  but still works.  Buy direct from the publisher because some places sell it for a much higher price.

 

Verbal child learning to read

Once your child is verbal, you will start to wonder how he is ever going to learn to read.  Here again science can help you.

There is a truly wonderful programme that used to be called HeadSprout and is now called MimioSprout.  The developer got taken over and the new owner changed the name.  It is a product for the mass market, but under the cover lurks a great deal of ABA.  It has great sound and graphics.  I found it fun.  My son loved it.
 

The programme allows you to repeat lessons.  Typical kids rarely need to do this and will speed to the end of the course.  Kids with ASD need lots of repetition and I was repeating lessons on average about 5 times.

A computer probably cannot teach an autistic child to read, but it can certainly help a great deal.

Numeracy

Having learned to talk and then read, the next big hurdle is to learn some maths.  For a typical kid you do not even have to think about this. Maybe you get called in to help with long division, but not with 1 + 1.

Again, a great mass-market web-based programme is here to help.  It is called Whizz.  It has lots of fun graphics and goes from the very basics up to the end of primary school.  It includes the full curriculum, so things like weights and measures, telling the time, interpreting graphs and charts are all included.  It is much more than just numeracy.  As with Headsprout, the key is to repeat the excercises before moving on.

If your typical child used Whizz, I think they would hardly need to go to maths class at school. In the US Whizz seems to be used a lot for home schooling. I first came across Whizz on a US home schooling website.

Again, this continues to be money very well spent.

 

 

Rats in the Basement - lab update #1

This may be only the 4^th post on this blog, but in the background research is actually quite far advanced.  A few hundred learned papers on, have there been any further epiphanies?

Well at the risk of sounding smug, I have to say yes, or least maybe.

 

When I started out in late January 2013, I knew that rats in the basement was not going to be an option; either my elder son would use them for target practice, or my wife would object.

My original plan was to rely on my powers of observation to guide my research and just draw on the pool of existing scientific research as needed to develop a plausible hypothesis, that could then be tested and quite likely rejected.  This is more like primary research, the fun type. I used to do a lot of this.  Primary research is used extensively in the business world and sometimes verges on espionage.

In primary research I now have two projects:

 

·         TRH and more specifically TRH analogs.  This looks very promising, but gets pretty complicated and there will be lots of citations.

·         Hypokalemic Sensory Overstimulation.  This may prove to be just a curiosity.

Secondary research is what most people do.  It is all about reading other people’s research and then either dutifully regurgitating it, or putting a new spin on it and taking it forward.  I used to this a lot and it can also be fun.  The interesting thing I learned is that two different people, or “expert” teams, could look at the same data and come to diametrically opposing conclusions.  This has great relevance to Applied Neurological Analysis, which as from post #1 is now officially known as ANA.
 

Researching TRH took me into the depths of research concerning a wide range of psychiatric disorders, addictions, epilepsy and even HIV-AIDS.  It also led me to read some much lighter weight studies that actually did have the word autism in them.  Then one evening, on Google Scholar, I was jumping between Hyperbaric treatment for autism and vitamin B12 injections and had about 20 windows open on my laptop.

 

Just as lithium-ion batteries can overheat and start smoking on Boeing 787s, it is also possible with your laptop.  Not wanting my research to be grounded, I picked up the pace.

 

I was reading a paper that was in effect junking the use of Methylcobolamin (Methyl-B12) injections in autism.  Then I saw that it mentioned a subgroup for which it appeared the therapy had indeed produced a measurable  positive effect.  The author hypothesized that in these children the B12 was somehow raising the level of Glutathione (GSH). A-Ha and what exactly is that?  All will be revealed in a later post.

 
This led to 2 developments:-
 

·         Open up an investigation into GSH

·         Note that sub-groups can exist in autism and so there just may be more to a “failed” clinical trial than meets the eye.

 
Having allowed the laptop to cool down, I did a trawl through the research on Omega 3 fish oil.  I am not a follower of Complementary and Alternative Medicine (CAM), but it turns out that its followers are big buyers of fish oil.

I used to take omega 3 capsules because I read they are good for your heart.  A friend recently asked us to pick up some special ones in London that are supposed to make your kid get higher marks at school.  It turns out that even my Mum used to be given cod liver oil and malt during World War 2.  I would have written “during the war”, but in many parts of the world, where you read this blog, it then raises the question “which one?”.

Having learned from my friend Colin, that you can actually be allergic to specific kinds of fish, I had discovered a few months back that I too have intolerance to farmed salmon and trout.  When I looked into what they feed the fish, I soon came to believe that this was a plausible cause of my symptoms.  So this means no more salmon and much less “natural” omega 3.  It turns out that some people are even allergic to the fish oil supplements as well, but thankfully not me.

I concluded that I have a ready use for a large batch of unwanted, long expiry dated fish oil, should I need one.  So I decided to add an Omega 3 to my secondary research and potentially add it to the primary research pile.  I do admit to starting with a sceptical bias.

As you can see, often you need both primary and secondary research for the same job, but for the moment at least, there are no rats in the basement.

 

 

P.S.

If a further dose of humour is required at this time of day, ponder the reaction of the Japanese airline executive from ANA (All Nipon Airways) who is googling to see how much PR he is getting due the Lithim-Ion batteries in his parked fleet of Boeing 787 Dreamliners. Colin will be famous in Japan, as he deserves to be, and the sales of fish oil will rise.