Testosterone: Epitestosterone Ratio: Cheating or Genes?

(repost from 01/2011)

The Case Against Lance Armstrong” is the title of an article in the January 24, 2011 issue of Sports Illustrated. The case that is made within this article is based on in large part on what a few people with gripes against Lance have said. The other “hard” evidence is based on several tests detailing a very high Testosterone:Epitestosterone ratio. Before 2005 the tests normal was considered up to 6:1 and was then lowered to 4:1. Several tests over the years, which may have been Lance’s were considerably higher than this.

According to SI “Three results stand out: a 9.0-to-1 ratio from a sample collected on June 23, 1993; a 7.6-to-1 from July 7, 1994; and a 6.5-to-1 from June 4, 1996.”

Each time the ratio was found to be high, the “B” Sample was tested and found to not confirm the preliminary test. The second test is usually a carbon isotope test that is more specific to studying the makeup of the individual’s testosterone.

While the article goes on to say that one high number (of the T:E ratio) should be a once in a blue moon occurrence, there are significant genetic factors that can come into play.  A 2008 article published in The Journal of Clinical Endocrinology & Metabolism titled “Doping Test Results Dependent on Genotype of UGT2B17, the Major Enzyme for Testosterone Glucuronidationshowed that if an individual had two alleles for the UGT2B17 gene, there was a large chance that they would not test positive for cheating even after having taken a large dose of synthetic testosterone. The estimates were that 40% of individuals could pass the ratio examination just by virtue of having two copies of this gene. On the other hand with mixed alleles (ins/del) or in the absence of  this allele there was a fair chance that the ratio would always be abnormal. Estimates were that in a normal population, up to 9-14% of people would have a false positive result and fail the test.

It seems that if you have the del/del or ins/del variations of alleles, you are going to pretty consistently fail the test. The authors suggest that this gene should be tested and the results modified based upon the genotype of the individual.

Understanding the purpose of the Testosterone:Epitestosterone ratio testing and doing at least a brief look at  factors that might affect this test, not just once but repeatedly are important when an article such as the SI one is written. This specific gene and its implication on testing is widely known and has been covered in a variety of journal articles. The Canadian Medical Journal detailed, in an editorial titled “Doping, Sport, and the Community“, the difficulties in testing for Growth Hormone abuse and Testosterone. The editorial also mentioned research I came across elsewhere which indicated that many Asians (up to 40%) had the version of this gene that would give a false negative.

So, let’s get all the evidence out. And let’s make sure the public sees all the scientific information on the validity and the problems that exist with this particular test. For another perspective on heroes in American culture, you can seek out one of George Carlin’s last specials in which he expresses his opinion on hero worship and in particular on Lance Armstrong, Tiger Woods, and Dr. Phil.

The next test is to determine if the song “Bike” by Pink Floyd was written in a drug free state. In case you can’t make them out the lyrics begin:

I’ve got a bike
You can ride it if you like
It’s got a basket
A bell that rings
And things to make it look good
I’d give it to you if I could
But I borrowed it

Available video of Pink Floyd’s Bike (blocked currently at Youtube)

and if Pink Floyd is just not your cup of tea. Here is Queen performing their song “Bicycle Race”

Overuse Injuries: All The Small Things (repost 10/2010)

Podiatry Management (October, 2010) has just published an article I’ve written titled  Overuse Injuries: All The Small Things . You are just another click away from the PDF version. This is a challenging article. It introduces mechanotransduction, a theory of cellular and tissue function, which is little known in the sports medicine community. The article touches lightly on this topic and then reviews the latest literature and theory on overuse injuries to bone and tendon.

The Needle - Kenneth Snelson
The Needle - Kenneth Snelson

The cellular level is where things start and where we will find many answers. I expect to add more details on the web site on mechanotransduction and mechanobiology for those with hardcore, deep science interest. The article is limited in size, but was longer than many published in PM Magazine. But, I didn’t even touch on the theory canalicular flow and osteocyte induction or mechanotransduction and control of stem cell development by matrix stiffness. Research in the field of mechanobiology is growing daily and the outlook is great that it will be fruitful.

Digital Radiology Data In The Office: Standards (Repost 09/2010)

Osirix Image
Osirix Image

X-rays, MRIs and The Mac

Digitization of Radiology Film

There has been a trend to the increasing digitization of radiology information. This works great on  Mac computers since Osirix Imaging Software has been a global favorite of radiologists for several years. In fact a 2007 white paper detailing the integration of this open source software at a hospital in Mannheim is available at:

http://images.apple.com/science/pdf/Radiology_White_Paper20070814.pdf

Osirix works wonderfully for 2D and 3D information. It is a 2D viewer, 3D viewer, 4d viewer (time dimension) and a 5D viewer (3D data + temporal and functional data) It can integrate images derived from 2 sources such as Cardiac PET/CT angiogram. X-rays, bone scans, pet scans, cat scans and more are readily viewable.  I’ve used Osirix for about 3 years and find it reliable and helpful. It is great for MRIs. I’ve found clinical problems, such as a torn plantar plate, that had previously been mistakenly read as normal. (Of course a physical examination should go a long way in leading one to suspect a plantar plate injury.)

The standard file format DICOM and over 20 other file formats are easily read using Osirix. The DICOM standard allows physicians using software and systems from different vendors to rapidly share imaging information. The only time Osirix will not work is if a proprietary format is used. The disks are sometimes hostilely marked “not compatible with Apple Macintosh computers”.  Since every radiology center has the capability of outputting a standard format file, and it is readable by their own Microsoft Explorer based software, I don’t know why anyone would limit the readability of the disk. In fact, there is no good reason not to use DICOM format. But if by chance a radiology center near you has made the mistake of not using DICOM, that error is quickly remedied with a call requesting a standard format “DICCOM” disk. Osirix development is open source and distributed under the GNU Lesser General Public License.

What is DICOM?

DICOM is a radiological information standard file format. It is the de facto standard used in all hospitals worldwide. The file format was developed in 1993 and used for a variety of medical image types including MRI, CT, and Pet scan. The image is compressible. The National Electrical manufacturers Association (NEMA) created the standard and these same manufacturers embed the capability of creating these standard file formats for cross platform interoperability.

DICOM can even store information on radiation exposure for examinations. It is dependent on the device manufacturer to properly implement this using the current addendum to the standard called the “Radiation Dose Structured Report“. Phillips and GE create a separate image with the total exposure listed. For more details see David Clunie’s Blog.

MEDX3D format is a new format with ongoing work to incorporate the upcoming format in the DICOM standard and in OSIRIX.

The NEMA online brochure explains the format in simple English: http://medical.nema.org/dicom/geninfo/Brochure.pdf

Links:

Osirix Imaging Software

Osirix for iPhone/iPod Touch

Radscaper – Dicom viewer via browser that doesn’t use ActiveX for windows and Linux. Uses a Java applet.

Windows DICOM Viewer: DICOMWorks 1.3.5

DICOM – Latest Standard (doc and pdf formats)

Future of DICOM –   http://medical.nema.org/dicom/geninfo/Strategy.pdf

What Going Digital Will Mean For the Dentist’s Office – from J Am Dent Assoc

Dave’s Places In Radiology – Extremely thorough site for radiology professionals

David Clunie’s Blog (also see his Medical Image Format Site) – discussions and many links to sites with technical details.

MRI View of Big Mac (http://www.youtube.com/watch?v=VT_siDqhls8)

Quadrupedal Human Gait (repost 09/2010)

Quadrupedal Humans
Quadrupedal Humans

Bipedalism (walking upright on two limbs) in hominids is considered a logical and efficient means of locomotion arrived at via hundreds of millions of years of evolution. At the newly instituted PLOS group of blogs a thorough post appearing on the newly moved blog Neuroanthropology describes Turkish individuals who are quadripedal and exhibit what is called Uner Tan Syndrome (UTS). There is some conjecture on the cause of this condition and on whether or not it is evolutionary atavism.

This syndrome was first discovered in 2005 by Üner Tan of Cukurova University in Turkey who is also a member of the Turkish Academy of Sciences.

I note that the quadripedal humans seem to be scurrying along at a fair clip. They are not wearing any coverings on their hands. From the photo it is difficult to determine what they wear on their feet. The video below does show some foot gear. At least some of the quadrupedal humans seem to have the forelimb contact on the heel of the hand, but others may contact further foreward.  I’m sure this will be looked at closer. Evolutionary analysis and better coaching may lead to improved 4 limb locomotion for these individuals. So far I have not come across any reports of any quadrupedal long distance endurance events.

This does appear to be a real syndrome however and the blog describes the symptoms and results of MRI and PET scans on subjects. The findings include:

“signs of cerebellar dysfunction including: intention tremor, dysdiadochokinesis (inability to execute rapidly alternating movements particularly of the limbs), dysmetria (lack of coordination of movement typified by under- or over-shooting the intended position), and nystagmus (involuntary rhythmic eye movement, with the eyes moving quickly in one direction, and then slowly in the other). However, the cerebellar signs are relatively mild, and they are no more pronounced in the quadrupeds than in the one affected brother who walks bipedally.”

My take on this is that the syndrome appears to be an inherited motor and sensory issue (HMSN). There are many disorders in this category with a variety of symptoms. Some of the more common ones include Refsum’s syndrome and Charcot-Marie-Tooth disease .

Both a BBC and PBS Nova documentary have been produced on this condition.

Links:

Neuroanthropology Blog Post on “Human Quadrupeds” by Greg Downs – thorough discussion, many reference links

John Hawks Discussion on “Turkish Tetrapods” in 2006

A New Syndrome With Quadripedal Gait Tan, U. Int J Neurosci. 2006 Mar;116(3):361-9.

Family That Walks on all 4s (NOVA show)

Why Here, Why Now, Why Old, Why Not New

Some database issues have made it imperative to recreate the blog comment by comment. And I may not be able to accomplish that. I’ve tried to choose the better ones from the past few years and added them in to the latest WordPress blog software. So that’s why you see some old stuff here.

And hopefully soon, you’ll see some newer material too.

I’ll edit and update the older material where needed.

Exercise Is Good For Your Brain (Repost)

repost (from November 2011)

Credit: © Eric Isselée / FotoliaCognitive decline with aging is an increasingly important research topic. This past November (2011) Science Magazine produced a special issue on the brain including   a summary article and a main article which discusses the impact on a specific neurodegenerative disease (spinocerebellar ataxia type 1) in mice.

A “mild” exercise regimen helped the mice live significantly longer. The effects lasted for a considerable time, even after stopping the exercise program. The disease studied has features in common with Alzheimer’s in that an insoluble protein that accumulates in nerves is involved. Exercise has been shown to have positive effects on Alzheimer’s disease and the research here on how exercise impacts the proteins and future exercise on a variety of growth factors produced during exercise may help in producing strategies for Alzheimer’s disease and numerous other degenerative diseases.

The accompanying summary article states:

“In addition to the benefits of exercise on brain health and cognitive function, it may promote slowing neurodegenerative disease progression. For example, exercise slowed the decline in cognitive abilities of Alzheimer’s disease patients and improved postural stability and balance in Parkinson’s disease patients.”

References:

Another Reason to ExerciseAaron D. Gitler. Science 4 November 2011: Vol. 334 no. 6056 pp. 606-607. DOI: 10.1126/science.1214714

Exercise and Genetic Rescue of SCA1 via the Transcriptional Repressor Capicua. John D. Fryer, Peng Yu et. al. Science 4 November 2011: Vol. 334 no. 6056 pp. 690-693 DOI: 10.1126/science.121267

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Walk Don’t Run: Ambling Along With 4.5 Million Year Old Flat Feet

by PRIBUT on OCTOBER 1, 2009

Ambling Along With 4.5 Million Year Old Flat Feet

A hominid species predating Lucy, (Australopithecus africanus) has been more fully described. Journalists have had first crack at the issue of Science in which the updated description of the species,  Ardipithecus ramidus (from 4.5 million years ago), appears. The rest of us could only see this issue late in the day.  The recently studied Ardipithecus specimens include the feet, which were clearly missing on Lucy (from 3.2 million years ago), but present among a limited set of other Australopithecus specimens. Ardipithecus was originally discovered in 1994 in Ethiopia.

The treasure trove of the day are the eleven fresh papers detailing  Ardipithecus and it’s (with a delay in publication for years) environment including botanical and other specimens found locally, the anatomy, and evolutionary conjectures all published in Science magazine. Details on excavation, locale, personnel, CT scans, three-dimensional reconstruction, dimensions and sizes of the specimens, were included in this comprehensive set of articles.

Ardipithecus was thought to live and spend time in trees, but would carefully climb rather than swing from the branches. Ardipithecus was also believed to spend time foraging for food, primarily plant based, on the ground while moving in a bipedal manner. Australopithecus was not a runner, nor is it likely with feet less well adapted  was Ardipithecus. Among other lower extremity differences between Homo erectus and Ardipithecus were flatter feet and an opposable big toe (metatarsus primus varus – actually  metatarsus primus adductus – a large angle in stance between the first and second metatarsal bones – but I’ll have to check out more photos and study the  articles in detail in Science magazine). If Ardipithecus twiddled her thumbs she could likely also twiddle her opposable big toes. Speaking of toes, one of the changes that is thought to make running possible for the later hominids was a shortening of the length of toes, in addition to an increase in arch height, and a host of other biomechanical changes.

An opposable big toe with a non-functional first ray makes for a decidedly different bipedal gait than even Lucy had. The tight grouping of the cuneiforms present in later hominids allowed the first ray to function effectively in weight transfer and propulsion rather than the little it could do as an opposable digit without stability in ground based bipedal gait. Of course a humanoid great toe does not offer much assistance in the trees. An important feature to note is that Ardipithecus did not knuckle walk, as can be determined from the wrist and hand structure, during bipedal gait, although the upper extremities were long. Nor did Ardipithecus appear to brachiate or swing through the tree branches.

Below are images of the upcoming cover of Science magazine with Ardipithecus on the cover and an image of Lucy missing her feet.

Update: Freely available articles at Science

Ardipithecus
Ardipithecus

 

 

 

 

 

 

 

Related Articles

Movement and Exercise Spurred Evolutionary Brain Development

In The Beginning: We Were Made To Stand Upright

Walk This Way (Early Foot Prints  of Homo erectus)

Additional References:

Fossils, feet and the evolution of human bipedal locomotion W E H Harcourt-Smith and L C Aiello. J Anat. 2004 May; 204(5) : 403–416.
  Walk Don’t Run

 

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Evolution and Exercise: What Made The Brain Get Bigger

by PRIBUT on AUGUST 3, 2009 (retrieved from Internet Archive )

Stimulating Brain Development: Evolution Of The Brain Spurred By Movement (a speculative hypothesis)

We previously mentioned the early hominid development of upright, obligatory, habitual bipedal posture mentioning the richer protein and calorie dense food which may have enabled better brain development. We’ll expand on that a bit with a “big think” and take it down a slightly different road. And we can have a bit of fun with a speculative hypothesis.

My thought (and hypothesis) is that exercise, viewed as aerobic movement, was the spur to development of a larger brain as is found in later hominids and modern humans. Tool making, enhanced socialization, all other more modern features and the larger cortex itself derive from motion, movement, and the positive effect that “exercise” has on the chemistry of the brain.

As we stop and think about what made the brain enlarge we hear those who say that bipedal movement freed up our hands. Now you can walk and juggle or do other tricks.  Another theory posits that early hominids could now carry food back to their tribe, make tools, ultimately jewelry and developed other useful talents. Whatever occurred likely was multi-factorial and not a simple single means event.

In keeping with Darwinian principles, it is incorrect to say that the environment created changes. We need to look to see what environmental features were taken advantage of by those best prepared to do so. Mutations are random, selection is purposeful, and geared towards the survival of those most fit for the environment. There are a variety of phenotypes present at any time, and those exhibiting desirable and helpful characteristics do survive and pass on those useful genes.

Mammalian brains produce BDNF (brain derived neurotrophic factor) which assists in neural plasticity and in the creation of new neural cross links. Humans today moving at high rates of oxygen uptake show that at up to 60% of maximum VO2, several things come into play. The first is an increase in Cerebral Blood Flow (CBF). The CBF increases as does the production of  BDNF and other compounds that among other effects stimulate brain growth and development. These other compounds include IGF-1 (insulin growth factor 1), VEGF (vascular endothelial growth factor), and FGF (fibroblast growth factor).

Bathing the brain in this enhanced biochemical “miracle grow” mix, likely would have resulted in superior neural growth and response for those who were best able to respond to this physical and neurological environment.  This seems to have been a contributing factor in the maximal development of the early hominid brain, and continued down through the hominid line.brain

 

 

 

 

 

 

Those most able to respond to the biochemical results of their activity of  motion, movement, and gathering would have become the smartest of the lot and been most likely to survive . They would be better suited for survival and more able to pass on their genes.  Bipedal movement in hominids was first to be short in duration. Lasting for only a limited distance and allowed for limited scavenging.  Ultimately it resulted in habitual and obligate bipedalism of longer duration, and finally in walking and then, later, running.

There have been debates over the energetics of bipedal motion versus brachiation and advantages over older forms of quadripedal locomotion. But with the thought that nothing gets wasted, if the energetics don’t balance perfectly it is probable that the energy itself that may not have been optimally efficient for walking, certainly was put to excellent use in the development, enhancement, and gradual evolution of the hominid and ultimately modern human brain.

Bipedal walking allowed the former tree apes a  better and more easily sustained motion. This  over the course of time, possibly led to persistence hunting, or at the least an expanded range for gathering, foraging, and then much later hunting. And the migration out of Africa was another sustained effort and may have stimulated brain development.

Sensory stimuli, socialization, diet, and many factors went into brain evolution and development. Then, as now, it is likely that the sustained efforts of moving increased focus, attention, and concentration. Creating mental maps of where they had been, and how to return home gave their small brains a work out. And speculating a bit, ultimately mental maps led to many other things and perhaps even primitive games of hide and seek.  Later came blind folded chess and google maps.

Many facets of evolutionary thought are interesting and valuable. Socialization and network theory, the role of sensory stimulation all are explorable, viable theories and played a major role in evolution. Here we’ve brought into play another facet of hominid evolution not previously described. The energetics and resultant neurochemical (and other changes) as a result of  motion, movement and exercise is a contributing and driving force for brain development and evolution. Put this in the context of the fact that everything moves and there is nothing entirely still in the universe, we have another small factor to consider about our world and how we and it have evolved.

So it seems we weren’t just born to walk or run. We were born to think, develop and evolve. In fact, we’ve evolved to evolve. And evolution continues today. If your thoughts stop with barefoot running, and you think our evolution stopped then, you’ve got a lot more thinking and catching up to do. Exercise and movement are good for what ails you, and assisted in the development of today’s modern human brain.

(Outline presented at American Podiatric Medical Association Annual Scientific Seminar. August 1, 2009. Toronto, Canada)

(Link on Wayback Machine – Internet Archive)