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mamamax
04-16-2010, 05:54 AM
Where are we going with this?

Once we hit the Intermedicate Risk Score ... it is as if we don't have the test at all as there is no predicting for "certain" what will happen. Scoliscore is in field testing now ... and chapter one in a very large book to come. And furthermore - the low scores cannot predict what may happen in old age. Scoliscore is proving (to me) to present more questions than it initially seems to answer.

Videos worth watching: http://www.spinecme.org/activity/942

rohrer01
04-16-2010, 04:42 PM
Thank you Mamamax for these videos. Very interesting. I'm left with the feeling here that what this Axial Biotech research is still doing is basically writing off the adult patient. Yes, it is VERY important to know what the adolescent curve is going to do before skeletal maturity. But either I am not understanding the information, or these tests have no value in predicting what a curve will do AFTER skeletal maturity. I was diagnosed at 16 with a 39* curve and told that I would progress to surgery level curve 40* by my 40's, which in fact I progressed to that level before reaching 30 years of age. When I went to the Twin Cities Spine Center in Minneapolis, MN, where Dr. Oglvie worked at the time, the magical number had changed from 40* to 50* for surgical intervention (thus my post about 50*). Even though I was in sever pain and only 29 years old the doctor that I saw would not touch me (Dr. Joseph Perra). I am now 41 years old and 46*, not to mention developing a lower thoracic curve now 28*, which was negligible as a teen. How do these studies play into this? Are they telling us as parents that if we can get our kids to skeletal maturity that there will be no progression and then just dismiss them? There is WAY more to this story than is being addressed here. For me, they hovered over me like vultures just waiting to see 40* so they could operate (Phoenix Children's Hospital), then when I reached 18 years old, they told me I would need surgery someday, probably in my 40's, bye, bye.

I realize that this testing is a very important tool for parents and doctors in making decisions on whether to brace an adolescent or do surgery on a smaller curve, knowing it will progress. But it does little to help that adolescent when they become adults, which we all do. Am I making any sense? I find it very frustrating, being that I have a 20 year old daughter that fell withing that 15 - 20* curve pattern and now refuses to even be evaluated because she was told her growth was complete and there was no chance of progression. The doctor went so far as to say that he didn't even consider her to be serious enough to be classified as scoliosis. This was not a specialist (he was a orthopedic surgeon in sports medicine) and I was sadly undereducated on treatments of scoliosis - and what kind of doctors to see and NOT to see. Now there is absolutely nothing that I can do to help her, even though she is starting to present with back pain.

Interesting findings, but not very helpful for those of us that are aging. The estrogen related thing that they said made girls more likely to progress than boys intrigued me, too. I have progressed about 12* total for both curves. During this time I was going to a chiropractor for treatments, BUT I was also going to a fertility specialist and taking all kinds of fertility drugs that interfere with estrogen production. It makes me wonder if either or both had a correlation, or was I just genetically predisposed to progress?

I know these are probably stupid questions, since the topic was about Adolescent Idiopathic Scoliosis. But, hey, adolescents turn into adults, so I don't think I'm too far off base.

Thanks again Mamamax for sharing the videos!

mamamax
04-16-2010, 07:58 PM
Some great thoughts and questions rohrer01. I wonder myself what application there may be for adults (if any). Hope to finish watching the videos this evening. Hopefully others will weigh in on this also. I would like to know if there is a way for us to track the field trial results, or if we will have to wait years for those results. If it works as well as some say it will then yes it can be very important in making treatment decisions for our youngest. The error rate is supposedly 1% ... which is great, unless one is in that 1% .. and seems no way of predicting that. Did you see in video #1 the suggestion that scoliosis is so driven by heredity that the term IS should be changed to familial scoliosis. Interesting. I really enjoyed your comments and found them thought provoking - I do not think you are way off base.

rohrer01
04-16-2010, 09:32 PM
Really how could it not be called familial scoliosis. I did not know anyone in my family had scoliosis until I participated in this very research study. It got everyone talking about it and I have at least 4 other people in my family with scoliosis. My aunt, although never diagnosed, obviously has kyphoscoliosis. My mom said she did it to herself because she was tall and wanted to be shorter than the boys. What a hoot! I love my mom, but some of the things she says. LOL ..So I'm thinking there's got to be a relationship there, also. The rest of us have the side bending kind.

There is another lady on here that actually had her family participate in the study as well. She has a daughter that meets the criteria for the "test" and they have done the test on her. She is just waiting for the results. I wish they would test boys, too. :( I worry a little bit about my grandson being that I have it and so does his mother. Look under the thread Axial Biotech Results are Here.... something along those lines. Very interesting indeed!

Thanks again!:D

mamamax
04-16-2010, 09:57 PM
rohrer01 - Yeah, what gives with leaving out the boys? Just finished watching all the videos to the end, including the Question/Answer session.

It was freely admitted that selection of the high end score (180) was arbitrary, and that an Intermediate score puts everything back to square one (we don't know what will happen). How many will end up with an Intermediate score, that is the question. If it turns out to be the majority of people, then we have gained precious little. I'm still not convinced this test is going to tell us any more than a good solid family history would.

I like your mom :-)

rohrer01
04-16-2010, 10:48 PM
Well, even if most of the kids tested get an intermediate score, it means a LOT for those that get a low end or high end score. The low enders don't get subjected to as much radiation, etc. and the high enders probably won't be put through the pain and stress of bracing. I'm afraid the middle scores, well, they will have to go with the current treatment options. But at least there is benefit for some of the kids out there. I would definitely have my kids tested if it had been available!

I like my mom, too. She thinks she knows, but she is silly sometimes. She thinks she caused my scoliosis from making me carry my saxophone to school every day. In my senior year of high school they actually made me quit band (the doctors). I lost out on the chance of a lifetime! I was one of four nationally accepted alto saxophonists to be chosen for a European tour and march in the Rose Bowl! I was devastated to say the least. It's just the doctor's at that time didn't know if I had a tumor and I was in a lot of pain. :(

Dingo
04-17-2010, 12:30 AM
At about the 2:00 minute mark Dr. Ogilvie says this,


"Well, once you know that it is a genetic disease how do you go about finding those genes?"

AIS is a genetic disease? Really? The "I" in AIS stands for Idiopathic which means of unknown cause. Put simply we don't know why some children have Scoliosis.

However that doesn't mean we can't make an educated guess as to what the cause might be. In the simplest terms Scoliosis, like all disease is caused by 1 of 3 things.

A) Heredity
B) Environment (usually damage)
C) A combination of A & B

According to American Family Physician (http://www.aafp.org/afp/2001/0701/p111.html) scoliosis hits 2% to 4% of children between the ages of 10 and 16.

How many harmful, genetic disorders hit that many children? Let's check Wikipedia and find out. Wiki: List of Genetic Disorders (http://en.wikipedia.org/wiki/List_of_genetic_disorders).

Click on any potentially fatal, childhood, genetic disorder and look for the prevalence. Hmmm.... not a single one hits 2% to 4% of children around the world like Scoliosis. In fact only a handful hit more than 1 child in 10,000. Many genetic disorders hit 1 child in millions.

Is Dr. Ogilvie's hypothesis correct that Scoliosis is caused by heredity? As long as the "I" remains in AIS we don't know. As for me I doubt it will be the first so I don't like the odds.

So what about B) Environment or C) Environment plus heredity? How many potentially fatal, childhood disorders or diseases are caused by either of those? Countless.

According to wikipedia there are 350 to 500 million cases of Malaria (http://en.wikipedia.org/wiki/Malaria) every year which kill between 1 and 3 million people. The flu (http://en.wikipedia.org/wiki/Influenza) kills 250,000 to 500,000 people per year. Think of all the common diseases that you got as a child. They were all environmental.

But what about diseases like Type 1 Diabetes? Type 1 runs in families so it's genetic, right? Nope. Mounting evidence points to a common virus as the cause (http://www.sciencedaily.com/releases/2009/03/090305141639.htm). Genes only play a role in susceptability.

What about a disease like Multiple Sclerosis? Even the name sounds genetic. Genes may play a role in susceptability but once again a common pathogen appears to be responsible (http://www.sciencedaily.com/releases/2010/03/100304165900.htm).

What about mental illness like Schizophrenia? Remember the flu that kills 250,000 to 500,000 people per year? Evidently it's also a trigger for Schizophrenia (http://www.sciencedaily.com/releases/2009/06/090609073032.htm) and Autism (http://www.news.com.au/mothers-flu-could-lead-to-mental-illnesses/story-e6frfkp9-1111113964576?from=public_rss).

The more you read the faster you'll realize that disease in young people is almost always caused by environmental damage. A disproportionate percentage of this is caused by pathogens. Germs and viruses are the undisputed heavyweight champions when it comes to taking down humans and they do so in a multitude of different ways.

Could a germ or virus deform the spine? Yep. Polio is a well known cause of Scoliosis. According to the link that LindaRacine posted the other day Tuberculosis can also cause spinal deformity.

HBO: Making The Crooked Straight (http://www.makingthecrookedstraight.org/)


Born in Long Island, New York and educated at John Hopkins-Dr. Rick Hodes has dedicated his life to helping heal the sick and poor of Ethiopia over the past 20 years. Many of his patients are stricken with tuberculosis of the spine, a disease that creates massive humps on the backs of its victims. Eventually they’re forced into permanent forward-bending posture, which in turn prevents their lungs from working properly, and if left untreated leads to death.

No doubt doctors are aware of dozens of different infectious diseases that damage the spine. It is easily possible that a common pathogen can cause damage which for reasons we don't yet understand leads to AIS. It's how I'm betting and I believe the odds are in my favor.

tonibunny
04-17-2010, 07:04 AM
I wish they would test boys, too. :(


Rohrer, are you sure they don't test boys? We had someone sign up at SSO who told us her son has been tested.

mamamax
04-17-2010, 08:51 AM
rorher01 & Tonibunny - maybe the original "mapping" didn't include boys? I don't know now ....

Dingo - Thanks for weighing in, was hoping you would. Would have liked to see you in that Question/Answer group! What if all the multi-factorial things wind up effecting the severity of the condition, but bottom line, a genetic defect is what allows that to happen?

Pooka1
04-17-2010, 09:29 AM
It would be next to impossible to distinguish between the following two scenarios:

1. faulty genes

2. faulty genes plus environmental trigger if the environmental trigger is ubiquitous.

The distribution patterns of AIS cases would be IDENTICAL between these two scenarios.

The simplest explanation that best describes the situation now is that it is genetic as Oglivie states outright though of course if there is an environmental trigger and someone ever identifies it, then that is an avenue of research for AIS prevention hopefully.

mamamax
04-17-2010, 09:39 AM
A genetic disorder is a disease that is caused by an abnormality in an individual's DNA. Abnormalities can range from a small mutation in a single gene to the addition or subtraction of an entire chromosome or set of chromosomes. To learn more about different genetic disorders, browse through the Genetic Disorder Library

http://learn.genetics.utah.edu/content/disorders/whataregd/

Dingo - Where is Dr. House when we need him? Anyway, ... we know environmental factors can alter DNA. So it would stand to reason that any small mutation could be further "altered" through environmental factors.

I hear that smoking can alter DNA ... question: is the altered DNA corrected upon cessation? If so ... it is promising to know that alteration can be corrected.

Wonder what all this is coming up with: http://learn.genetics.utah.edu/content/health/ngs/

Anyone know what the Howard Hughes Medical Institute Precollege Science Education Initiative for Biomedical Research is doing (if anything) in the area of scoliosis research?

Dingo
04-17-2010, 09:54 AM
mamamax


Thanks for weighing in, was hoping you would. Would have liked to see you in that Question/Answer group! What if all the multi-factorial things wind up effecting the severity of the condition, but bottom line, a genetic defect is what allows that to happen?

Most cases of Scoliosis occur sporadically. For that and many other reasons I believe that the majority of AIS cases are not rooted in a genetic defect. However it's possible that certain rare types of AIS are caused by genes. It's also possible that particular genes may make a child susceptible to environmental damage that triggers Scoliosis. As I've mentioned before Leprosy is caused by a bacterial infection but genes create increased susceptability to the germs that cause it (Gene that makes people vulnerable to leprosy discovered (http://www.scienceblog.com/cms/gene_that_makes_people_vulnerable_to_leprosy_disco vered)).

BTW none of this means that the Scoliscore isn't a useful test. Scoliscore isn't designed to find the genes that trigger Scoliosis. It's designed to find the genes that allow Scoliosis to inflict serious damage should it occur. Think of it this way, when Haiti was hit by a 7.0 earthquake over 200,000 people died. When Chili was hit by an 8.8 earthquake only 500 people died. The difference in casualties was largely a result of building standards. If these earthquakes hadn't occured nobody would have died in either city. For the same reason if a child doesn't have Scoliosis his/her Scoliscore doesn't matter.

BTW if I had the good fortune to end up in a Q&A session with Dr. Ogilvie I could shut him down inside of a minute. If he came under direct, simple questioning from me or anyone else he would backpeddle from his claim that Scoliosis was caused by heredity.

tonibunny
04-17-2010, 10:04 AM
I was contacted by the Director of Comms at Axial Biotech a few weeks ago, and she said I could contact her at any time with questions about Scoliscore. I'll ask her if she could possibly come here so you can have a discussion Dingo :)

mamamax
04-17-2010, 10:11 AM
mamamax
Most cases of Scoliosis occur sporadically. For that and many other reasons I believe it's highly unlikely that the majority of AIS cases are rooted in a genetic defect. However it's possible that certain rare types of AIS are caused by genes. It's also possible that particular genes may make a child susceptible to environmental damage that triggers Scoliosis. As I've mentioned before Leprosy is caused by a bacterial infection but genes create increased susceptability to the germs that cause it (Gene that makes people vulnerable to leprosy discovered (http://www.scienceblog.com/cms/gene_that_makes_people_vulnerable_to_leprosy_disco vered)).

I agree that it sometimes appears that certain cases are "sporadic" but I have no idea whether or not most cases are ... didn't one of the docs in the video indicate that sometimes one may have to go back nine generations to find a familiar link?


BTW none of this means that the Scoliscore isn't a useful test. Scoliscore isn't designed to find the genes that trigger Scoliosis. It's designed to find the genes that allow Scoliosis to inflict serious damage should it occur. Think of it this way, when Haiti was hit by a 7.0 earthquake over 200,000 people died. When Chili was hit by an 8.8 earthquake only 500 people died. The difference in casualties was largely a result of building standards. If these earthquakes hadn't occured nobody would have died in either city. For the same reason if a child doesn't have Scoliosis his/her Scoliscore doesn't matter.

Yes, the test is not a diagnostic tool - but rather, a tool to help doctors and patients assess treatment options. If one falls into the low end of the score, we presume no treatment will be needed (barring any unforeseen environmental factors?). The true test of that will involve several years of gathering data and tracking patients.


BTW if I had the good fortune to end up in a Q&A session with Dr. Ogilvie I could shut him down inside of a minute. If he came under direct, simple questioning from me or anyone else he would backpeddle from his claim that Scoliosis was caused by heredity.

Well, there was some sputtering going on when offered a question about how bracing may effect any one of the categories ... if I remember correctly one doc said - we simply do not know & Ogilvie said something like - we are not permitted to comment on that at this time. So I think you would have found similar answers to your questions but certainly, you would have sent them home with something to think about :-)

Pooka1
04-17-2010, 10:52 AM
In re Oglivie's response that he wasn't permitted to answer, what has been characterized as "sputtering" was the careful qualification of his remarks and intense desire not to go beyond the data. This is a good skill to have and would greatly benefit some folks in this sandbox.

He was asked if a score of greater or equal to 195 was "useful" in that we can just assume they will all get to surgical territory just as they claim a very low score is useful. The reason he said he was not permitted to say that is they don't have enough data points at the high end to be as sure as their conclusions at that lower end and he explained this exact point earlier in the talk.

There is no subterfuge or hedging or anything like that. Axial Biotech is being careful not to let the researchers speculate beyond the data which would undermine the credibility of the results.

Pooka1
04-17-2010, 11:03 AM
Other points in the talks that I though were interesting:

1. The genetic data largely agree with the Lonstein and Carlson (1984) empirical/observational data about the rate of progression increasing as the angle increases (linear at small angles and exponential at large angles). That is consistent with a genetic control on eventual angle achieved.

2. Some 80% of patients based on school screenings are low risk and will never progress. This means ANY treatment on low angles will appear to be at least 80% effective. Clear and others exploit this fact with unsuspecting bunnies who don't know this.

3. Of these "low risk" low Scoliscore patients, > 99% won't progress to > 40*. But as we have seen recently, some experienced surgeons are telling people that it isn't unusual that curves as low as the low to mid 30s* at maturity will progress to surgery territory even in young adults. And indeed we have seen several testimonials to that effect on the forum. So the true useful question may be how many progress to some angle below 40* wherein a large fraction of those patients will never progress to surgery territory. As it stands now, this cutoff (<40*) may be of relatively little use.

4. Non AIS people are related back at the 24th generation but AIS cases are related back to the 9th generation. This would seem to be very strong evidence for genetic control although I don't know if doing this work in Utah with a history of polygamy has completely biased the sample. I wish they did that in a state with a more rational history.

5. The data are biased at the low end (very few cases less than 20*) and biased at the high end (didn't pass along data of folks who made it to ~40* but didn't progress to surgery at that time). That will affect the conclusions.

6. Suken A. Shah is in the running for most devastatingly handsome orthopedic surgeon. :D

mamamax
04-17-2010, 11:38 AM
I was contacted by the Director of Comms at Axial Biotech a few weeks ago, and she said I could contact her at any time with questions about Scoliscore. I'll ask her if she could possibly come here so you can have a discussion Dingo :)

That would be great - Thanks Toni!

Pooka1
04-17-2010, 01:07 PM
Just looking at the error range on the scoliscore graph that Newton presented... it is maximal at intermediate scores. If those are one standard deviation high and low then the RISK of progression at a score of 150 will fall between about 52% and about 68% 95% of the time. Five percent of the time time it will fall outside that range.

I'd also like to see their rate of Type 1 and Type 2 errors in table format. That would be interesting.

Pooka1
04-17-2010, 01:09 PM
The best hope for this thread is if Pnuttro comments. She has previously commented on Scoliscore and I just wonder if she has any further comments.

mamamax
04-17-2010, 01:46 PM
The aim of Scoliscore is the accurate prediction of progression. As data is collected, analyzed, and patients followed throughout the years - other applications may surface (possibly for adults).

Surgical treatment does not always result in a pain free outcome. I've often wondered why. Pondering genetic predisposition to progression leads me to consider that perhaps while fusion and instrumentation physically holds the curve - such does not necessarily eliminate the predisposition for progression. If a spine is genetically predisposed to progression, will it "try" to progress regardless of instrumentation? There are cases where progression may continue even after surgery. I would imagine this is quite painful.

So - it may be important to be able to accurately identify those who fall into a genetically predisposition to progress category (or very high Scoliscore), in order to better understand who will and who will not continue to experience pain following surgery. And possibly, the Scoliscore could one day help to provide information in that area as well.

Then again, as someone who will always face the possibility of surgery, I could just be guilty of pondering too much and too deeply.

Pooka1
04-17-2010, 01:59 PM
I think we can surmise from the average outcome of patients with just a curve (i.e., kids) versus those with a curve plus a bunch of other damage from the curve or just from aging that long term post op pain is related to the presence of the bunch of other damage.

Most kids are usually off pain meds in a few weeks and most adults are not. That's a pattern right there.

Not proof or even evidence but a suggestion consistent with the data.

LindaRacine
04-17-2010, 05:39 PM
There are cases where progression may continue even after surgery.

If the spine is fused and the implants hold, the curvature will not progress. What you're probably referring to is some people who had fusion surgery before the era of implants. As far as I know, these people did not report pain at any higher rate than the general public.

rohrer01
04-17-2010, 05:48 PM
It is would be next to impossible to distinguish between the following two scenarios:

1. faulty genes

2. faulty genes plus environmental trigger if the environmental trigger is ubiquitous.

The distribution patterns of AIS cases would be IDENTICAL between these two scenarios.

The simplest explanation that best describes the situation now is that it is genetic as Oglivie states outright though of course if there is an environmental trigger and someone ever identifies it, then that is an avenue of research for AIS prevention hopefully.

I tend to agree with Pooka1 on this matter. She is the mother of identical twins who not only both had scoliosis, but also both progressed to surgical intervention. Not genetic? Hmmm... I'm guessing, Pooka1, that the girls did not manifest "identical" symptoms? Maybe that is where environment comes in to play - even if it is environment in the womb.

And, yes, there are many genes that we have, that have either environmental triggers and/or consequenses. Look at sickle cell anemia. Those people that carry one good "gene" and one bad "gene" seem to be malaria resistant (I don't have a citation - repeating from memory). Those that have two bad copies end up with sickle cell anemia.

The thing that confounds me a bit is that the genetic component of this disease is expressing itself as autosomal dominant, recessive, and I believe they mention X-linked. This can only lead one to assume that there are several "genes" involved and we are looking at multiple players in this game. I have scoliosis and so does my daughter (although not as severe). Is this a case of autosomal dominancy or one good copy one bad copy? There are also a slew of other disorders connected to scoliosis (connective tissue disorders, Marfan's for one). Maybe there are several types of "AIS" that have a similar phenotype but lack the same genotype (sorry if sounding redundant).

To address the "I" in AIS. That is what, I believe they are trying to figure out. Idiopathic - coming from the same root word as "idiot" - only suggests that "they don't know". Well what is science all about, but to figure out the unknown? When we know, we will be better equipped to deal with it.

If families with known cases of scoliosis consistently come up with genetic markers that are absent in the non-scoliotic population, you can pretty much assume that it is genetic, whether there is an external trigger or not. Then when those rare cases surface where there is no such genetic link, I think we can reserve the term AIS for those cases and those cases alone.

I had never heard of scoliosis. When I found out about it, no one in my family thought it was a big deal. When I took part in this study, then my family started talking. We have four cases, plus mine, within a two generation span one way or the other from me and one case of Marfan's. How can one NOT say that it is not genetic, at least in some families? Maybe there truly are AIS cases, but I think they will be harder and harder to find, now that there are genetic markers to go by. The truly non-AIS patients are the ones that benefit from the test.

The boys were left out of the initial scoliscore testing because they believe that estrogen may be an influence on the likelihood of progression. It was in one of the videos.

Just my thoughts.;)

rohrer01
04-17-2010, 05:59 PM
If the spine is fused and the implants hold, the curvature will not progress. What you're probably referring to is some people who had fusion surgery before the era of implants. As far as I know, these people did not report pain at any higher rate than the general public.

People with the old Harrigton rods, I believe, continue to progress because those rods tended to bend. I don't know how the "fusion" allows it. I have a friend with congenital scoliosis who was 90+ degrees before Harrington's were implanted. She obtained correction to around 60* and she has progressed again, I'm not sure how far, but she looks a FAR cry from 60* just looking at her, poor thing. She is too far gone to have repeat surgery as it has affected her heart and lungs. She is on Oxygen and is basically waiting to die. I wish she would see a specialist out here that would tell her that, or not, so she can get help if it really isn't too late. But that's what her doctor's where she lives told her. I think she is tired of fighting scoliosis. It's been one wicked ride for her, her whole life. :(

Pooka1
04-17-2010, 06:04 PM
I tend to agree with Pooka1 on this matter. She is the mother of identical twins who not only both had scoliosis, but also both progressed to surgical intervention. Not genetic? Hmmm... I'm guessing, Pooka1, that the girls did not manifest "identical" symptoms? Maybe that is where environment comes in to play - even if it is environment in the womb.

BINGO! Very astute. Are you in a science field or just good at it? :)

I agree.


And, yes, there are many genes that we have, that have either environmental triggers and/or consequences. Look at sickle cell anemia. Those people that carry one good "gene" and one bad "gene" seem to be malaria resistant (I don't have a citation - repeating from memory). Those that have two bad copies end up with sickle cell anemia.

Yes, sickle cell persisted because people with the trait and who didn't have the full-blown disease were more resistant to malaria than others without the trait. So the gene persisted. Maybe the same happened with scoliosis genes. I wonder what the advantage might have been that co-occurred with the scoliosis gene?


The thing that confounds me a bit is that the genetic component of this disease is expressing itself as autosomal dominant, recessive, and I believe they mention X-linked. This can only lead one to assume that there are several "genes" involved and we are looking at multiple players in this game. I have scoliosis and so does my daughter (although not as severe). Is this a case of autosomal dominancy or one good copy one bad copy?

I am not a biologist but I think that is straight dominance. I always have to look up autosomal when I see the word. Pnuttro could explain this well - she is a biomedical researcher.


There are also a slew of other disorders connected to scoliosis (connective tissue disorders, Marfan's for one). Maybe there are several types of "AIS" that have a similar phenotype but lack the same genotype (sorry if sounding redundant).

Good question. I don't know.


To address the "I" in AIS. That is what, I believe they are trying to figure out. Idiopathic - coming from the same root word as "idiot" - only suggests that "they don't know". Well what is science all about, but to figure out the unknown? When we know, we will be better equipped to deal with it.

Right. They will crack this nut eventually or I certainly hope so!


If families with known cases of scoliosis consistently come up with genetic markers that are absent in the non-scoliotic population, you can pretty much assume that it is genetic, whether there is an external trigger or not. Then when those rare cases surface where there is no such genetic link, I think we can reserve the term AIS for those cases and those cases alone.

Or maybe a spontaneous mutation and then it is still straight genetic. I think that's why Oglivie can state with some confidence it is genetic at this point.


I had never heard of scoliosis. When I found out about it, no one in my family thought it was a big deal. When I took part in this study, then my family started talking. We have four cases, plus mine, within a two generation span one way or the other from me and one case of Marfan's. How can one NOT say that it is not genetic, at least in some families? Maybe there truly are AIS cases, but I think they will be harder and harder to find, now that there are genetic markers to go by. The truly non-AIS patients are the ones that benefit from the test.

I had a similar experience suddenly finding relatives on BOTH sides of the family with scoliosis and even at least one fusion. People don't mention it sometimes or family members may just hear that a relative has a back problem without the word "scoliosis" being mentioned. I think if they radiographed (not just asked) all relatives of every case it would become very obviously a genetic disease. We know already that self reporting leads to huge errors.

As for Marfans, my kids are being monitored for that though they don't meet the diagnostic criteria now. That one at least has a known ~25% spontaneous mutation rate so it can appear sporadically though it is a dominant trait and much more often is simply in the family. If my kids ever get that diagnosis, it will likely be a spontaneous mutation as I know of no other case of people with that diagnosis or anyone dying in their 40s from aortic dissection on either side of the family.


[/The boys were left out of the initial scoliscore testing because they believe that estrogen may be an influence on the likelihood of progression. It was in one of the videos.

Just my thoughts.;)

Those are good thoughts in my opinion!

Pooka1
04-17-2010, 06:09 PM
People with the old Harrigton rods, I believe, continue to progress because those rods tended to bend. I don't know how the "fusion" allows it.

The rods bend because they didn't fuse because the rods weren't enough to allow fusion to occur as far as I know. Linda will edify me if that is wrong. That is why surgeons will cite the pedicle screw as the major advancement in this field. The rate of pseudoarthrosis is very low with screws and in fact the implants are so good that 95% of kids need no physical restrictions at all and still get a solid fusion. That's pretty good.

LindaRacine
04-17-2010, 06:12 PM
People with the old Harrigton rods, I believe, continue to progress because those rods tended to bend.

I never heard of a single case where Harrington rods bent inside of a patient. If you ever have a chance to handle a Harrington rod, try to bend it. :)

Pooka1
04-17-2010, 06:20 PM
I never heard of a single case where Harrington rods bent inside of a patient. If you ever have a chance to handle a Harrington rod, try to bend it. :)

Well don't they break from repeated bending?

LindaRacine
04-17-2010, 06:34 PM
Well don't they break from repeated bending?

Yes, but the bending is on the microscopic level, and it's not a permanent bend. (In other words, a rod may bend a millimeter one way, then back again, over and over.) It would not allow the curve to progress more than a few degrees, unless the rod breaks, in which case, all bets are off.

Pooka1
04-17-2010, 06:35 PM
Yes, but the bending is on the microscopic level, and it's not a permanent bend. (In other words, a rod may bend a millimeter one way, then back again, over and over.) It would not allow the curve to progress more than a few degrees, unless the rod breaks, in which case, all bets are off.

Ah okay. I get that. Thanks.

rohrer01
04-17-2010, 06:42 PM
The rods bend because they didn't fuse because the rods weren't enough to allow fusion to occur as far as I know. Linda will edify me if that is wrong. That is why surgeons will cite the pedicle screw as the major advancement in this field. The rate of pseudoarthrosis is very low with screws and in fact the implants are so good that 95% of kids need no physical restrictions at all and still get a solid fusion. That's pretty good.

Well, that makes me glad that they didn't do the "fusion" on me at 16. I came within a hairs width of having it done and they decided not to at the last minute. It would have been Harrington's. I may have the fusion soon, because of adult progression - which, by the way wasn't mentioned in the videos, except to say our X-rays were hard to find in the 40* range and not fused (I guess we're the throw away crowd) - but at least I will get the "better" technology if you can say that about any fusion.:confused:

I have a B.S. in Cell and Molecular Biology and minors in Mathematics and Chemistry. Just an FYI. Haven't worked since graduation. :( But I still LOVE genetics!

rohrer01
04-17-2010, 06:45 PM
Also, I think that it IS possible for a fusion to bend, if the rods don't hold. Bone can be bent over time. Think about Chinese baby girl feet.... ouch!

Pooka1
04-17-2010, 06:48 PM
I have a B.S. in Cell and Molecular Biology and minors in Mathematics and Chemistry. Just an FYI. Haven't worked since graduation. :( But I still LOVE genetics!

It shows in your thinking. You and Pnuttro are our two molecular people then. Cool. :cool:

rohrer01
04-17-2010, 08:23 PM
It shows in your thinking. You and Pnuttro are our two molecular people then. Cool. :cool:

Not so "cool" as RUSTY!:p I find this stuff fascinating. But afraid of misstating things based on flawed memory. I don't have enough time to do the research to be as accurate as I'd like. But at least understanding a little bit of the concept behind it helps me follow along. I'm an expert my NO means.

I'm guessing you are in the math field, since you state a lot of statistical information, etc...?:p

rohrer01
04-17-2010, 08:54 PM
What I was suggesting in me and my daughter's case is maybe a case of codominance, where when both alleles are present, one is not dominant over the other. You would see this in a blending of colors in flowers, I believe. That would explain why my daughter has a much smaller curve than I do (a blending so to speak). Just another observation.

It will be interesting to know how many genetic markers actually contribute to scoliosis. My daughter was also tested for Marfan's and I have a slight mitral valve prolapse (still within normal parameters). I think they may end up having broad markers, that cover a variety of connective tissue disorders, then more and more specific ones that pertain specifically to scoliosis. Maybe the broader markers would indicate that a person may be susceptible to more of an environmentally enduced scoliosis - (like my shy aunt slouching to be shorter than the boys - although I think she still would have developed kyphoscoliosis). I hope their findings help take the stigma off of the self-induced scoliosis theory that my family throws at me. It's quite discouraging to get blamed for progression because you did or didn't do something. It affects a child's self-esteem growing up - believe me, I heard it all the time as an adolescent. I am thankful that someone is doing something about it!

I would like to understand what information exactly they are using to compile the scoliscore? I think Axial Biotech owes us participants better explanations than they are giving us, since this was a completely voluntary and uncompensated study. EVERYONE wasn't from Utah. My doctor recomended me to join the study. I am originally from the Northwest Coast. But..... I do have a long family history in the Mormon Church, right back to the founders and yep, up to my own father. Maybe, had I known that they were going to take most of their population from Utah, I should have told them this. Maybe it would have disqualified me from the study? I'd also like to know how they came up with only nine generations of mutation that connects us all? Did anyone besides Pooka1 catch that? Maybe the research we should be conducting now is how many of us have Mormon ancestors?

Seriously, I'm not saying that to be a smart-aleck. There are populations with specific genetic issues. Look a Tay Sachs, Sickle Cell, etc... it happens when you get too much interbreeding in a gene pool. It makes the gene pool small. Then when random mutations occur, they get passed around and quickly.

Anyway, I'm done rambling for now. I have THINGS to do... You all have a nice night!!!:D

Pooka1
04-17-2010, 10:12 PM
Not so "cool" as RUSTY!:p I find this stuff fascinating. But afraid of misstating things based on flawed memory. I don't have enough time to do the research to be as accurate as I'd like. But at least understanding a little bit of the concept behind it helps me follow along. I'm an expert my NO means.

I'm guessing you are in the math field, since you state a lot of statistical information, etc...?:p

No I'm not a mathematician and I am definitely not a stats person! I think that if you need fancy statistics to interpret your data then you did the wrong experiment. But I'm in the minority on that. :D

I'm a researcher in earth sciences. Thus my obligate reliance on bio types and molecular types. My few courses in biology, biochem, microbio etc. don't help me much with the thoroughgoing medical biochem topics that float by occasionally in this little sandbox. :)

We do have an MPH here on the group who is a real asset in my opinion especially when discussing the literature and its limitations.

Dingo
04-17-2010, 10:12 PM
tonibunny


I was contacted by the Director of Comms at Axial Biotech a few weeks ago, and she said I could contact her at any time with questions about Scoliscore. I'll ask her if she could possibly come here so you can have a discussion Dingo

Right on! If a Q/A thread with Axial ever gets started count me in! :)

Dingo
04-17-2010, 10:24 PM
rohrer01

Just because a disease hits two identical twins doesn't indicate that it's caused by heredity. I believe the concordance rate for Leprosy among identical twins is something like 60% to 80%. Leprosy is not a genetic disorder. It's caused by a bacterial infection and can be easily cured with antibiotics.

Another thing to keep in mind is that just because a disease hits a family particularly hard doesn't mean it's genetic. Family members share a lot more than genes.

Case in point:
High Blood Pressure Could Be Caused By A Common Virus, Study Suggests (http://www.sciencedaily.com/releases/2009/05/090514221915.htm)


(May 16, 2009) — A new study suggests for the first time that cytomegalovirus (CMV), a common viral infection affecting between 60 and 99 percent of adults worldwide, is a cause of high blood pressure, a leading risk factor for heart disease, stroke and kidney disease.

Long story short, wash your hands. :eek:

Pooka1
04-17-2010, 10:33 PM
It will be interesting to know how many genetic markers actually contribute to scoliosis. My daughter was also tested for Marfan's and I have a slight mitral valve prolapse (still within normal parameters). I think they may end up having broad markers, that cover a variety of connective tissue disorders, then more and more specific ones that pertain specifically to scoliosis. Maybe the broader markers would indicate that a person may be susceptible to more of an environmentally induced scoliosis - (like my shy aunt slouching to be shorter than the boys - although I think she still would have developed kyphoscoliosis). I hope their findings help take the stigma off of the self-induced scoliosis theory that my family throws at me. It's quite discouraging to get blamed for progression because you did or didn't do something. It affects a child's self-esteem growing up - believe me, I heard it all the time as an adolescent. I am thankful that someone is doing something about it!

Wow that's really sad. It's a shame when folks don't understand the medical conditions of their kids. I think it is physically impossible for you to have done anything to prevent or encourage progression on your own. It seems obvious.


I would like to understand what information exactly they are using to compile the scoliscore? I think Axial Biotech owes us participants better explanations than they are giving us, since this was a completely voluntary and uncompensated study.

Well he mentioned that they used known case outcomes and some complex math by which I think he means used massive computing to vary the prevalence of perhaps hundreds of marker gene sequences to figure out which combination of which sequences produces the best empirical fit to the known outcomes. They then converted that to a numerical score arbitrarily. It's complex because they are trying to optimize the fit using an equation with 53 (or more) variables. That can only be done by computer. That's my guess as to what is going on there.


EVERYONE wasn't from Utah. My doctor recommended me to join the study. I am originally from the Northwest Coast. But..... I do have a long family history in the Mormon Church, right back to the founders and yep, up to my own father. Maybe, had I known that they were going to take most of their population from Utah, I should have told them this. Maybe it would have disqualified me from the study? I'd also like to know how they came up with only nine generations of mutation that connects us all? Did anyone besides Pooka1 catch that? Maybe the research we should be conducting now is how many of us have Mormon ancestors?

I was incorrect about assuming all test subjects were from Utah as you point out. But manyybe most are... we don't know. I certainly hope that isn't the case as I think it has been shown that between five and ten men fathered every child presently in the state. :D But seriously, I think that is a potential problem that hopefully will not compromise the millions spent on developing this test.

The 9th generation thing for AIS compared to the 24th generation in the random population is very compelling if it holds up.


Seriously, I'm not saying that to be a smart-aleck. There are populations with specific genetic issues. Look a Tay Sachs, Sickle Cell, etc... it happens when you get too much interbreeding in a gene pool. It makes the gene pool small. Then when random mutations occur, they get passed around and quickly.

Yes that is a live issue as far as we can tell. Have they published this stuff yet in a peer-reviewed journal? I think I recall Pnuttro predicting that with 53 markers, it will never reach the printed page.

Pooka1
04-17-2010, 11:02 PM
She is the mother of identical twins who not only both had scoliosis, but also both progressed to surgical intervention. Not genetic? Hmmm... I'm guessing, Pooka1, that the girls did not manifest "identical" symptoms? Maybe that is where environment comes in to play - even if it is environment in the womb.


The best available evidence on scoliosis and twinning is probably this metadata paper indicating ~73% concordance between identicals and ~36% concordance between fraternals (= any sibling/sibling pair).

http://journals.lww.com/spinejournal/Abstract/1997/09010/Scoliosis_in_Twins__A_Meta_analysis_of_the.14.aspx


Results. Thirty-seven sets of twins were monozygous, and 31 sets were dizygous. Concordance was 73% among monozygous twins and 36% among dizygous twins. The difference is statistically significant at P < 0.003. Curve severity could be compared in 20 sets of monozygous twins and 16 sets of dizygous twins. Among monozygous twins, there was a correlation coefficient of r = 0.399 (P < 0.126). Curve pattern comparison was not statistically significant.

Conclusions. Monozygous twins have a significantly higher rate of concordance than dizygous twins, and the curves in monozygous twins develop and progress together. Based on these data, there is strong evidence for a genetic etiology for adolescent idiopathic scoliosis.

(emphasis added)

A genetic component is widely accepted by researchers as far as I know based on multiple lines of evidence, not just twins studies.

Dingo
04-17-2010, 11:07 PM
At the 1:22 mark.

Dr. James Ogilvie

If you can stretch a multigenerational family pedigree and then look at the relatedness among people eh... you can... eh... most people are eh... related to about the 24th generation you have a common ancestor. Those people with idiopathic scoliosis are related to a common ancestor at about the 9th generation. So it is a very clearly distinct population that has idiopathic scoliosis.

I agree with Dr. Ogilvie. Children with Scoliosis probably do share common genes that make them susceptible to Scoliosis. This means that Scoliosis works the same way as every other disease that mankind has discovered.

Case in point:
Scientists pinpoint flu gene (http://www.telegraph.co.uk/health/3538487/Scientists-pinpoint-flu-gene.html)


An unlucky combination of "vulnerable" genes could explain why some people recover from the flu overnight and others struggle to shake off the virus for weeks. Infectious disease experts in Australia have identified a mix of genes that make people eight times more likely to suffer for longer, and experience severe symptoms, once they fall ill.

rohrer01
04-17-2010, 11:57 PM
Dingo,
Are you implying that you think that AIS is VIRAL? Maybe if there is a lot of close exposure to other family members, I might buy into that theory. My family lacks the closeness of many families, and why my daughter and not my sons? If what you suspect is true, the mother would most likely have to be infected with the scoliosis virus before or during pregnancy. Did my paternal grandmother pass her virus to my dad and then, eh??? Well, that one doesn't work (and my dad doesn't have scoliosis). Maybe it's floating in the environment, who knows? Viruses are nasty little bits of RNA that like to make trouble for us.

I do see your point that environmental factors do play distinct roles in disease. I will never argue that one. However, if some outside factor were to in fact "cause" scoliosis, then it would cause it in everyone predisposed to getting it. Here we are, right back to genetics. As it stands we will have to play the wait and see game and see what shows up. I guess I just don't quite understand what your argument is for playing down the genetic component to this? The evidence thus far, says YES, there is a genetic link to this. I think if the geneticists out there look at it from their perspective and people like you, who are looking at other causes look at it from your perspective, we might just come to a common agreement. I have seen no proof as of yet that suggests that it is NOT genetic. I see no proof so far as to suggest a possible source of infection, so to speak. So again, I don't quite follow where you are going with this debate. Sorry.

And to anwer Pooka1's question. Nothing I say here is peer reviewed unless I quote it and tell you where I'm getting it from. I'm just mulling this whole thing over in my mind and trying to make sense of it all. Just as most everyone else is doing. I have nothing to prove. I am just gaining insight in to how everyone is viewing this and expressing my opinion based on what I think and hear in and OUT of the forum.

Also, if, in fact, this study was tainted by an overabundance of "mormon" study subjects, we could be viewing Mormon, no longer as a religion, but as an ethnicity, akin to the "Jewish" population with its commom diseases.

Again, just rambling my thoughts. I should go to bed before I get myself into trouble. ;)

rohrer01
04-18-2010, 12:14 AM
rohrer01

Just because a disease hits two identical twins doesn't indicate that it's caused by heredity. I believe the concordance rate for Leprosy among identical twins is something like 60% to 80%. Leprosy is not a genetic disorder. It's caused by a bacterial infection and can be easily cured with antibiotics.

Another thing to keep in mind is that just because a disease hits a family particularly hard doesn't mean it's genetic. Family members share a lot more than genes.

Case in point:
High Blood Pressure Could Be Caused By A Common Virus, Study Suggests (http://www.sciencedaily.com/releases/2009/05/090514221915.htm)



Long story short, wash your hands. :eek:


Just curious as to what the ratio of Leprosy was in the general sibling population. I'm wondering also if monozygotic twins "share" more than other siblings including dizygotic twins? Areas where Leprosy is common are poor areas where people bathe in the same water as each other and often drink that same water. Leprosy is a bacterial condition due to poverty and lack of available clean water, sewage, etc.

Do you work for the CDC? You should!;) You might really be on to something from the "germ" perspective. I just don't see any evidence pouring in, yet. I don't really think the CDC would think that a scoliosis epidemic would be something high on their priority list. JMHO

wash, wash, wash!!! I agree. Don't kill the good "bugs" though. We need them, too.:D

rohrer01
04-18-2010, 12:21 AM
No I'm not a mathematician and I am definitely not a stats person! I think that if you need fancy statistics to interpret your data then you did the wrong experiment. But I'm in the minority on that. :D



Statistitians are called Mathemagicians...:D

You can fudge the figures in any study. Just throw out the few bits of data that don't fit the curve and viola! Just how many "bits" are getting thrown out? How many are allowed to be thrown? :eek:

tonibunny
04-18-2010, 04:48 AM
People with the old Harrigton rods, I believe, continue to progress because those rods tended to bend. I don't know how the "fusion" allows it :(

I've got an old Harrington Rod, I've had it for 25 years and it's not moved an inch and I've never had any trouble from it. There are tons of people out there like me, but you only ever hear about the ones who have developed problems (who are in fact the minority!) because the others are out there living their lives. If people do progress, it's because their underlying fusion isn't solid.

Pooka1
04-18-2010, 08:58 AM
Statistitians are called Mathemagicians...:D

That's a good one. I try for a clean result one way or the other.


You can fudge the figures in any study. Just throw out the few bits of data that don't fit the curve and viola! Just how many "bits" are getting thrown out? How many are allowed to be thrown? :eek:

Well that's data selection and unless they say they did it and have a very good reason, it constitutes scientific misconduct and should result in a paper being withdrawn.

I certainly hope they have at least one and hopefully two mathematical biologists and at least one statistician review that work. I don't know exactly what they are doing but it seems like they found a few hundred markers that occurred in various combinations in various patients with differing curve trajectories. They then took various combinations (300C50 for example) using massive computing assets to fit various perhaps even weighted combinations of these markers until they empirically got the best fit to the observed data. So it ended up being a 53 variable equation as the best fit. They then had it kick out a number between 0 and 200 for various regions of this curve. But I think a potential issue is whether that type of equation could eve possibly yield a unique solution if that is what they are doing.

I don't know what they did but that's my guess.

Let's see if they ever publish. Maybe Pnuttro will be right and it won't reach the printed page. Just reaching the press conference stage has a long history of going nowhere.

Dingo
04-18-2010, 10:35 AM
rohrer01


Are you implying that you think that AIS is VIRAL?

Viral infections are a known cause of spinal deformities in both animals and humans. On the flip side no childhood, genetic disease hits 2% to 4% of the global population. Not one. IMHO scientists should mine where they've found gold before, not on a barren landscape.

You might find these two stories interesting.

Scoliosis epidemic in Jamaica (http://bases.bireme.br/cgi-bin/wxislind.exe/iah/online/?IsisScript=iah/iah.xis&src=google&base=MedCarib&lang=p&nextAction=lnk&exprSearch=5672&indexSearch=ID)


Thus, in Jamaica, there has been almost an epidemic of idiopathic scoliosis which started around 1963 and began to fall off after 1982.

Indoor heated swimming pools: the vulnerability of some infants to develop spinal asymmetries years later. (http://www.ncbi.nlm.nih.gov/pubmed/17108419)


Evidence reported in an earlier paper suggests that infants introduced to indoor heated swimming pools in the first year of life show an association with spinal asymmetries including progressive adolescent idiopathic scoliosis (AIS) and in normal subjects vertical spinous process asymmetry.

rohrer01
04-18-2010, 10:38 AM
That's a good one. I try for a clean result one way or the other.



Well that's data selection and unless they say they did it and have a very good reason, it constitutes scientific misconduct and should result in a paper being withdrawn.

I certainly hope they have at least one and hopefully two mathematical biologists and at least one statistician review that work. I don't know exactly what they are doing but it seems like they found a few hundred markers that occurred in various combinations in various patients with differing curve trajectories. They then took various combinations (300C50 for example) using massive computing assets to fit various perhaps even weighted combinations of these markers until they empirically got the best fit to the observed data. So it ended up being a 53 variable equation as the best fit. They then had it kick out a number between 0 and 200 for various regions of this curve. But I think a potential issue is whether that type of equation could eve possibly yield a unique solution if that is what they are doing.

I don't know what they did but that's my guess.

Let's see if they ever publish. Maybe Pnuttro will be right and it won't reach the printed page. Just reaching the press conference stage has a long history of going nowhere.

I'm not accusing Axial Biotech of this. I'm just saying it can be done, and really who is going to catch anyone at doing this if the data is just deleted. I know that is one reason for peer review, but if the data "doesn't exist" so to speak, well? We are trusting that the PhD's in the world are all honest. And we know, like everyone else, some have an agenda. You see it in drug companies all the time putting out bad drugs. They are not all honest. I'm just hoping the Axial Biotech people are.

rohrer01
04-18-2010, 10:56 AM
That's data selection and unless they say they did it and have a very good reason, it constitutes scientific misconduct and should result in a paper being withdrawn.



I had one professor call it "massaging the figures". It wasn't really important at the time, just practice work. But it does, in my opinion, teach a dishonest work ethic, even though she was just trying to get through the class and be nice and not make everyone do it over again.

I did undergraduate research, and if something like that came up, It was DOCUMENTED and the experiment repeated by another individual. The work I was doing was for publishing and peer review. We were very careful.

I'm not sure that just havig 53 markers will disqualify the paper from being published, if the information is consistent and accurate. I think that the problem they may face is with their study sample. They may have to make a revision about their "population" and repeat the study on a purely non-mormon group and see if the results compare. But I still think that they could publish the "mormon" study as long as they specify that it will be repeated with a more randomized group of subjects. Skewing is very bad for data interpretation, but not always unuseful. I think, if they did it right, they should have no problem publishing, granted they acknowledge the above "problems".

mamamax
04-18-2010, 11:08 AM
Post surgical pain is a confusing topic. I read the surgical boards quite a bit. This is something both surgeons and patients struggle with. As I have said before, as someone with scoliosis - surgery could always be in my future (a fact I cannot ignore), so - while my heart and soul is engaged in the non surgical ... I try to keep an eye on the surgical as well since at this time, medical science is at a loss to accurately predict my future. And I do wonder what the continued information gathered by Scoliscore may offer all patients as data is collected and analyzed - hopefully patients will be followed throughout their lifetimes.

Some who undergo spinal fusion report being pain free. And some report continued pain, even though fusion is solid and instrumentation successful. So - barring instrumentation or fusion failure, sometimes, post surgical pain is still an issue - why? Sometimes non surgical methods prove most promising, and other times a complete failure - why?

Some published articles indicate that when instrumentation is removed - that there are times when a fused spine will progress. Why is that? Could all these questions be answered by knowing the genetic predisposition to progress throughout a lifetime?

That is my question. If there is any truth in the theory, then this may prove as a guide regardless of treatment option.

If the theory is correct - this also has application to explaining bracing (and other non surgical) failures and/or successes.

In any case, I think there is a need to know regarding the prediction of progression in the mature spine. And maybe Scoliscore will be able to provide that information, provided data is collected, analyzed and patients followed throughout their lifetimes.

We may find that those with low to intermediate Scoliscores fair better regardless of treatment options due to a lack of genetic predisposition to progress? That would be very valuable information in making our decisions in treatment options.

mamamax
04-18-2010, 12:06 PM
Dingo - you would have made an exceptional scientist I think.

Your offered articles were thought provoking. And plays into an earlier post offered which, in the simplest terms, outlined what may effect the outcome of any medical condition:



A) Heredity
B) Environment (usually damage)
C) A combination of A & B

A medical doctor I highly respect added world view to that list. Anyway the offered articles look like a combination of genetics and environmental factors to me. Singapore is currently reporting a higher incidence of scoliosis. Radiation is a known environmental factor (probably combined with heredity) and the radiation levels there are quite high according to the World Health Organization: http://www.who.int/uv/intersunprogramme/activities/uv_index/en/index3.html I don't know about Jamaica but it would be interesting to know the radiation levels in that region between the years 1963-1982.

Pooka1
04-18-2010, 02:52 PM
I'm not accusing Axial Biotech of this.

Right I know that. There is no way any of us can know that.


I'm just saying it can be done, and really who is going to catch anyone at doing this if the data is just deleted. I know that is one reason for peer review, but if the data "doesn't exist" so to speak, well? We are trusting that the PhD's in the world are all honest. And we know, like everyone else, some have an agenda. You see it in drug companies all the time putting out bad drugs. They are not all honest. I'm just hoping the Axial Biotech people are.

Yes there is some history of subterfuge when so much money has been spent and so much more money is riding on the outcome.

It's interesting to see that some surgeons have stock in the company. It would be very instructive if we were told if/when they ever dumped stock going forward. I didn't realize Axial Biotech was publicly held.

Pooka1
04-18-2010, 03:01 PM
I'm not sure that just having 53 markers will disqualify the paper from being published, if the information is consistent and accurate. I think that the problem they may face is with their study sample. They may have to make a revision about their "population" and repeat the study on a purely non-mormon group and see if the results compare. But I still think that they could publish the "mormon" study as long as they specify that it will be repeated with a more randomized group of subjects. Skewing is very bad for data interpretation, but not always unuseful. I think, if they did it right, they should have no problem publishing, granted they acknowledge the above "problems".

Well now I am not so sure the ~9600 samples were dominated by Mormons but if it is then it might be an issue. I think this business might have to do with "founder effect" thought that might not be bad not being a biologist, geneticist, etc., I can't be sure.

In any case, I can't imagine they will repeat the study... it is millions and millions to date as far as I can tell.

Pooka1
04-18-2010, 07:05 PM
Hmmm... I'm guessing, Pooka1, that the girls did not manifest "identical" symptoms? Maybe that is where environment comes in to play - even if it is environment in the womb.

Curve characteristics in monozygotic twins with adolescent
idiopathic scoliosis 3 new twin pairs and a review of the literature

Lodewijk W van Rhijn1, Edwin J P Jansen1, Chris M T Plasmans2 and
Ben E E M J Veraart3

Departments of Orthopaedic Surgery, 1University Hospital Maastricht, P.O. Box 5800, NL-6202 AZ Maastricht, The Netherlands

ABSTRACT – Most authors state that there is strong
evidence for a genetic origin of adolescent idiopathic
scoliosis (AIS). This conclusion is mainly based on the
fact that the rate of concordance for AIS in monozygotic
twins is signiŽ cantly higher than that in dizygotic
twins. However, it is of interest to determine whether all
elements of scoliosis formation are genetically predetermined.
If this were the case, there would perhaps be less
place for closed treatment.

We surveyed the literature for monozygotic twin pairs
in which both members suffered from idiopathic scoliosis
and added 3 pairs from our own patient group. The
total group consisted of 32 twin pairs.
We found that gender, direction of the convexity, the
level of the apex and the kyphotic angle were determined
more by genetic factors than the lateral Cobb
angle of the scoliotic curve. This suggests that variations
in the environment may affect the curve patterns
in monozygotic twins.

(emphasis added)

rohrer01
04-18-2010, 09:09 PM
Curve characteristics in monozygotic twins with adolescent
idiopathic scoliosis 3 new twin pairs and a review of the literature

Lodewijk W van Rhijn1, Edwin J P Jansen1, Chris M T Plasmans2 and
Ben E E M J Veraart3

Departments of Orthopaedic Surgery, 1University Hospital Maastricht, P.O. Box 5800, NL-6202 AZ Maastricht, The Netherlands

ABSTRACT – Most authors state that there is strong
evidence for a genetic origin of adolescent idiopathic
scoliosis (AIS). This conclusion is mainly based on the
fact that the rate of concordance for AIS in monozygotic
twins is signiŽ cantly higher than that in dizygotic
twins. However, it is of interest to determine whether all
elements of scoliosis formation are genetically predetermined.
If this were the case, there would perhaps be less
place for closed treatment.

We surveyed the literature for monozygotic twin pairs
in which both members suffered from idiopathic scoliosis
and added 3 pairs from our own patient group. The
total group consisted of 32 twin pairs.
We found that gender, direction of the convexity, the
level of the apex and the kyphotic angle were determined
more by genetic factors than the lateral Cobb
angle of the scoliotic curve. This suggests that variations
in the environment may affect the curve patterns
in monozygotic twins.

(emphasis added)

It is very interesting that my husband (who is a mechanic - but likes to try to understand these things) and I were talking about this very subject. I would want to know especially the GENDER of the monozygotic twins in a particular study. Have you ever heard of X-inactivation? That is in females. We only need one X chromosome and the other one just "inactivates" itself and has very little gene expression coming from it. It can be seen as a blob at the edge of the nucleus using stain and a standard microscope on the "oil" setting. Quite fascinating. If, as it has been suggested in one of the videos, that at least one scoliosis "gene" is X-linked. You would see that not all of the monozygotic girls would get scoliosis unless both X's had a bad allele. X-inactivation is completely random and occurs sometime in early embryonic developement, if my memory serves me well. Boys, on the other hand, have only one X and they need it (assuming they don't have a multiple X syndrome of some type). So in the male monozygotic twin population, you would expect to see BOTH twins suffer from scoliosis 100% of the time (outside factors excluded), if it is in fact X-linked. There may be other genes that are autosomal (not on a sex chromosome) and in these cases, environment, as Dingo has suggested would be the deciding factor for gene expression. Pnuttro can chime in here and correct me at any time!!;)

I've invited my friend, who is a PhD Molecular Biologist to lunch. I will definitely be bringing this up to see what she thinks. Her forte is cell division, but I'm sure she will have some very good insight.:D

Pooka1
04-19-2010, 05:58 AM
It is very interesting that my husband (who is a mechanic - but likes to try to understand these things) and I were talking about this very subject. I would want to know especially the GENDER of the monozygotic twins in a particular study. Have you ever heard of X-inactivation? That is in females. We only need one X chromosome and the other one just "inactivates" itself and has very little gene expression coming from it. It can be seen as a blob at the edge of the nucleus using stain and a standard microscope on the "oil" setting. Quite fascinating. If, as it has been suggested in one of the videos, that at least one scoliosis "gene" is X-linked. You would see that not all of the monozygotic girls would get scoliosis unless both X's had a bad allele. X-inactivation is completely random and occurs sometime in early embryonic developement, if my memory serves me well. Boys, on the other hand, have only one X and they need it (assuming they don't have a multiple X syndrome of some type). So in the male monozygotic twin population, you would expect to see BOTH twins suffer from scoliosis 100% of the time (outside factors excluded), if it is in fact X-linked. There may be other genes that are autosomal (not on a sex chromosome) and in these cases, environment, as Dingo has suggested would be the deciding factor for gene expression. Pnuttro can chime in here and correct me at any time!!;)

Yes and I think it is called Lyonization. Different x-chromosomes become activated in each twin and can account for large differences including that one has a genetic disease and the other doesn't. That last bit blows the minds of some folks because the kids are identical.

The putative Jamaica "AIS" increase is almost certainly not related to the AIS sensu stricto that accounts for a fairly constant 2-4% rate in the US and likely the rest of the world. If they were the same then we would be seeing similar excursions up and down in other places. While many places have no data, I think we have enough data on enough places to say the Jamaica "epidemic" is completed unrelated to the typical AIS case and proves nothing w.r.t. an environmental trigger for AIS cases everywhere else and at all other times. Also, we need to consider that the Jamaica case is just a reporting change, not an AIS incidence change as far as I can tell. One guy reported it and I can't find anyone else publishing a verification so it may not even be real.

The constancy of AIS rates in space and time suggests that if there is an environmental trigger, it is ubiquitous and therefore ineradicable. So the best hope defaults to genetics.

Lots and lots of red herrings get thrown around in this sandbox because we only have a few people with any relevant training.


I've invited my friend, who is a PhD Molecular Biologist to lunch. I will definitely be bringing this up to see what she thinks. Her forte is cell division, but I'm sure she will have some very good insight.:D

Cool!

rohrer01
04-19-2010, 09:44 AM
Post surgical pain is a confusing topic. I read the surgical boards quite a bit. This is something both surgeons and patients struggle with. As I have said before, as someone with scoliosis - surgery could always be in my future (a fact I cannot ignore), so - while my heart and soul is engaged in the non surgical ... I try to keep an eye on the surgical as well since at this time, medical science is at a loss to accurately predict my future. And I do wonder what the continued information gathered by Scoliscore may offer all patients as data is collected and analyzed - hopefully patients will be followed throughout their lifetimes.

Some who undergo spinal fusion report being pain free. And some report continued pain, even though fusion is solid and instrumentation successful. So - barring instrumentation or fusion failure, sometimes, post surgical pain is still an issue - why? Sometimes non surgical methods prove most promising, and other times a complete failure - why?



Some published articles indicate that when instrumentation is removed - that there are times when a fused spine will progress. Why is that? Could all these questions be answered by knowing the genetic predisposition to progress throughout a lifetime?

That is my question. If there is any truth in the theory, then this may prove as a guide regardless of treatment option.

If the theory is correct - this also has application to explaining bracing (and other non surgical) failures and/or successes.

In any case, I think there is a need to know regarding the prediction of progression in the mature spine. And maybe Scoliscore will be able to provide that information, provided data is collected, analyzed and patients followed throughout their lifetimes.

We may find that those with low to intermediate Scoliscores fair better regardless of treatment options due to a lack of genetic predisposition to progress? That would be very valuable information in making our decisions in treatment options.

I'm trying to find where Pooka1 gave a good explanation of this. Can't find it, but it sums up to the fact that juveniles have flexible spines. As we grow older, the bend in the spine causes damage. As the adult spine stiffens and damage increases, pain can occur. After doing surgery on an adult, the "damage" that was generated over years of having the deformity is likely the cause of the pain. Maybe some people just have less damage from their deformity. If the damage isn't severe, then they have a better outcome.

This is kind of a weird way to think of it. But in the US it is common decency for most women to wear a bra, if they are able, as it is viewed as obscene to show the nipple. The results of wearing a bra over years of time are that adhesions form to actually make the breast keep its shape (I learned this in Lamaze class). In order for a mother to nurse easier, it is to her advantage to pull gently on the breast and break some of those adhesions (again, according to my Lamaze instructor). If this is true of the breast, could it not be true of the spine, and how much more so! The body does all kinds of things to try to stabilize itself, including creating new tissue. I have, for example a massive muscle on one side of my neck, and practically no muscle on the other. It's a fact. My body grew tissue to be able to hold my head up since it comes out of my shoulder girdle at about a 46* angle. Now you go and straighten the spine that has grown all this extra tissue, and lacks tissue in vital areas. I would expect some would get pain. I think it would be an individual thing. Just my thought on that one.;)

rohrer01
04-19-2010, 09:45 AM
Oh, not to mention uneven wear on the disks, spinal degeneration and things lilke that.

mamamax
04-19-2010, 05:28 PM
I'm trying to find where Pooka1 gave a good explanation of this. Can't find it, but it sums up to the fact that juveniles have flexible spines. As we grow older, the bend in the spine causes damage. As the adult spine stiffens and damage increases, pain can occur. After doing surgery on an adult, the "damage" that was generated over years of having the deformity is likely the cause of the pain. Maybe some people just have less damage from their deformity. If the damage isn't severe, then they have a better outcome.

This is kind of a weird way to think of it. But in the US it is common decency for most women to wear a bra, if they are able, as it is viewed as obscene to show the nipple. The results of wearing a bra over years of time are that adhesions form to actually make the breast keep its shape (I learned this in Lamaze class). In order for a mother to nurse easier, it is to her advantage to pull gently on the breast and break some of those adhesions (again, according to my Lamaze instructor). If this is true of the breast, could it not be true of the spine, and how much more so! The body does all kinds of things to try to stabilize itself, including creating new tissue. I have, for example a massive muscle on one side of my neck, and practically no muscle on the other. It's a fact. My body grew tissue to be able to hold my head up since it comes out of my shoulder girdle at about a 46* angle. Now you go and straighten the spine that has grown all this extra tissue, and lacks tissue in vital areas. I would expect some would get pain. I think it would be an individual thing. Just my thought on that one.;)

Maybe I'm not using the correct terminology? Actually, what I'm trying to understand is - whether or not an individual has a pre-programmed genetic predisposition for curvature. Like each of us has a genetic predisposition to achieve our maximum standing height at maturity.

In other words - could I have a genetic predisposition to a given curvature (cobb angle). And if so, then say my spine was fused before it reached that genetic goal ... would the spine still try to reach that goal (even though it couldn't), trying to do so (fused) may be painful just as a matter of physics?

Pooka1
04-19-2010, 07:55 PM
In other words - could I have a genetic predisposition to a given curvature (cobb angle). And if so, then say my spine was fused before it reached that genetic goal ... would the spine still try to reach that goal (even though it couldn't), trying to do so (fused) may be painful just as a matter of physics?


I don't see how any predisposition to a certain Cobb angle could possibly matters after fusion assuming no pseudoarthrosis. As a matter of material science (bone).

Dingo
04-19-2010, 10:45 PM
Mamamax


could I have a genetic predisposition to a given curvature (cobb angle)

Since we don't know for sure it could be a lot of things.

You might have a gene that...

A) Predisposed your spine to grow curved
B) Predisposed the muscles around your spine to pull in a particular direction which in turn caused your spine to grow curved
C) Predisposed you to a common viral infection that damaged your nervous system and caused your spine to grow curved

There are so many possible explanations. I think when Dr. Moreau's blood test (http://pico.sssup.it/files/allegati/2004_1469.pdf) comes out a lot of these questions are going to be cleared up.

Dingo
04-19-2010, 11:06 PM
Mamamax


you would have made an exceptional scientist I think.

Thanks, now I'm blushing. :o I don't know how good I'd be as a scientist but if I worked in that field I'd get a job in Scoliosis research pronto. From the outside looking in it appears that a whole chunk of the field is based on silly science. Scoliscore may or may not be a good test for progression risk. However Dr. Ogilvie's assertion that AIS is triggered by heredity is going to be proven false. Except in rare cases kids aren't born to be sick. When a child is sick something happened to him/her.

Speaking of which:
How many years have we read stories where scientists claimed that Autism was caused by genes? WHOOPS! They were wrong. Today the focus is shifting away from heredity and towards environment.

California's Autism Increase Not Due To Better Counting, Diagnosis (http://www.sciencedaily.com/releases/2009/01/090108095429.htm)


"It's time to start looking for the environmental culprits responsible for the remarkable increase in the rate of autism in California," said UC Davis M.I.N.D. Institute researcher Irva Hertz-Picciotto, a professor of environmental and occupational health and epidemiology and an internationally respected autism researcher.

rohrer01
04-20-2010, 01:17 AM
Dingo,
I think the truth is somewhere in the middle. As I studied genetics in college, there seems to be too much mounting evidence to discredit it. It used to be believe that eye color was dominant, recessive and was controlled by only a couple of genes and the two light eyed parents could not have a child with dark brown eyes. The study of genetics has come a long way. It has since been discovered that eye color is controlled by many genes and indeed two light eyed parents CAN have a brown eyed child. My sister has blue eyes, her husband has hazel eyes and they have a son with dark broun eyes. I also have a friend with LIGHT green eyes and her husband has blue eyes, they also have a child with dark brown eyes. Sorry, it wasn't the milkman, the kids look just like both parents. I think the point I'm trying to make is that genetics is a little more complicated than you are seeing it. I think scoliosis research should be pursued from all angles. Not every child is born healthy, there are MANY genetic diseases out there. I realize that your argument is that there aren't any that affecto SO much of the population. Well, maybe this is the only one because so many different genes are involved. Every curve is different, therefore mutations could be different. If you classified scoliosis according to curve type, you wouldn't have such a high percentage. I think that scoliosis is just a VERY broad term for many causes of a crooked spine. Idiopathic just means they don't know. It doesn't mean it is the same disease. I commend you. You are a very good thinker.

rohrer01
04-20-2010, 01:26 AM
Maybe I'm not using the correct terminology? Actually, what I'm trying to understand is - whether or not an individual has a pre-programmed genetic predisposition for curvature. Like each of us has a genetic predisposition to achieve our maximum standing height at maturity.

In other words - could I have a genetic predisposition to a given curvature (cobb angle). And if so, then say my spine was fused before it reached that genetic goal ... would the spine still try to reach that goal (even though it couldn't), trying to do so (fused) may be painful just as a matter of physics?



I think that would be REALLY hard to prove, especially when they are able to move the spine around on growing children and even on adults like yourself. If this were true, your spinecor brace would cause you pain rather than alleviate it. :)

mamamax
04-20-2010, 05:46 AM
If this were true, your spinecor brace would cause you pain rather than alleviate it. :)

Exactly - Unless ... my unique blueprint for progression had already been achieved and my threshold for pain normal vs hyper sensitive and in the absence of any extenuating environmental factors.

Pooka1
04-20-2010, 05:54 AM
Most published research studies published by scientists working in their own fields are false. There are huge swaths of knowledge as yet unavailable to scientists and not for lack of trying.

Given that, the chances of lay people advancing the ball down the field are vanishing. It's not impossible but there is such a gaping chasm of knowledge with lay folks that if they did hit on an actual answer to any complex medial question it would almost certainly be purely by chance.

It is thus unseemly in the extreme when lay people with no relevant training accuse working scientists of pursuing "silly" science. It merely serves to highlight the huge gaping chasm of knowledge associated with lay people about complex medical subjects.

ETA: It is one thing to be angry and scared about your child's diagnosis and lament the lack of a cure to date. But that doesn't make it right to blindly attack the good guys working towards a cure in a shoot-the-messenger approach.

Pooka1
04-20-2010, 09:24 AM
I think the point I'm trying to make is that genetics is a little more complicated than you are seeing it. I think scoliosis research should be pursued from all angles. Not every child is born healthy, there are MANY genetic diseases out there. I realize that your argument is that there aren't any that affecto SO much of the population. Well, maybe this is the only one because so many different genes are involved. Every curve is different, therefore mutations could be different. If you classified scoliosis according to curve type, you wouldn't have such a high percentage. I think that scoliosis is just a VERY broad term for many causes of a crooked spine. Idiopathic just means they don't know. It doesn't mean it is the same disease. I commend you. You are a very good thinker.

This is a very rational analysis in my opinion.

Scoliosis is different than other genetic diseases in that 80% or better have such a small curve (some of which regress completely) that it doesn't affect any person's life in any way. Perhaps most of these kids NEVER AT ANY POINT realize they have it. Under those circumstances, there is no rational reason to suggest that it wouldn't rise to a incidence rate of 2-4% of the population (or better). There is no downside for 80% of people who have scoliosis. None whatsoever. The real question might be why ISN'T the incidence rate HIGHER than 2-4%, not why is it so high. Thus there is nothing in that observed incidence rate per se to undermine a genetic control as has been argued.

The constancy of this incidence rate in space and time is a very strong argument for the genetic basis of scoliosis which, as far as I can tell, is widely accepted among researchers which are the people best positioned to know one way or the other. That doesn't mean they do know but they are clearly in the best position to know.

That said, I think scoliosis might be a sort of birth defect like monozygotic twinning is referred to as a birth defect by some. The rate of monozygotic twinning is constant in space and time which suggests it is a birth defect that may be driven in whole or part by a very widespread (and therefore ancient) set of highly conserved genes. Maybe it just came along with the homeobox genes for general body plans. Who knows. The main difference between monozygotic twinning and scoliosis is that the former is truly and completely random whereas scoliosis has a very definite familial component, again consistent with a genetic control albeit of more recent origin. Evidence for this is the relatedness diagram showing the AIS cases are related back to he 9th generation whereas non-AIS people are related back to the 24th (on average) though the "Mormon effect" has to be ruled out for those particular data.

I am unaware of any research to date that is inconsistent with a genetic control on scoliosis. If anyone knows of any I'd like to see it. Thanks in advance.

Dingo
04-20-2010, 09:51 AM
Rohrer1


I think the point I'm trying to make is that genetics is a little more complicated than you are seeing it.

I hear what you are saying. I try to keep my ideas simple because otherwise it's hard to make a point in a thread. However even if we looked at complicated interactions between genetics and the environment the story would still the same. Organisms work tirelessly to optimize the health and fitness of their offspring.

Environmental factors weigh heavily in modulating gene expression in humans (http://www.eurekalert.org/pub_releases/2008-04/ncsu-non042208.php)


By studying gene expression of white blood cells in 46 Moroccan Amazighs, or Berbers – including desert nomads, mountain agrarians and coastal urban dwellers – the NC State researchers and collaborators in Morocco and the United States showed that up to one-third of genes are differentially expressed due to where and how the Moroccan Amazighs live.

The team uncovered specific genes and pathways that are affected by lifestyle and geography. For example, they found respiratory genes were upregulated, or turned on, more frequently in the urban population than in the nomadic or agrarian populations.

This makes sense, Idaghdour says, as urban dwellers deal with greater amounts of pollution in the city and encounter more difficulties with diseases like asthma and bronchitis. So it stands to reason that certain respiratory genes in city dwellers go into overdrive while staying quiet in rural and nomadic populations, he adds.

I live in Arizona which is blistering hot in the summer. I remember the day that we hit 122 degrees! My wife and I are of Northern European descent so we have very light skin. Interestingly enough our son with Scoliosis has skin that is a quarter shade darker than either of us. That's probably a result of gene expression combined with an extreme environment. His skin turned on genes to protect his body from the heat.

And no we don't need to do a paternity test. Except for the fact that he's 4 feet tall Scott looks like my clone. :)
Here is a video of Scott doin' a front flip. (http://img260.imageshack.us/img260/5767/scottjump.mp4)

Pooka1
04-20-2010, 03:12 PM
How to tell the difference and triage claims...

Science:
Tentative
Looks for disproof
Observation determines proof
Belief structure modified by observation
Self modifying —attempts to correct errors

versus

Pseudoscience:
Absolute knowledge
Looks for proof
Truth determines observation
Belief structure unchanging
No changes — repeats errors

http://astro.physics.sc.edu/pseudoscience.html

mamamax
04-20-2010, 05:04 PM
Dingo - great link. Thanks. Made me think: I used to say everything was relative ... lately it looks as if it might be better to say - It's all genetic and also relative to the environment. :D

The list of environmental factors grows daily ... some are rather "out there." The human organism is the greatest mystery (perhaps) of all.

http://www.lotusimmortal.com/experiments_showing_effect_of_co.htm

While I don't expect to see reference to the above Quantum biology in Scoliosis Journal within my lifetime - the work does provide some food for thought ... Love the story about two wolves. Rather deep - eh?

mamamax
04-20-2010, 05:33 PM
Dingo - your son is a Beautiful little boy! What is he saying at the end of the video? Too Cute!!

Dingo
04-20-2010, 10:41 PM
Mamamax

Mostly I read about disease and illness because of my son's Scoliosis. However occasionally I read about physics. Holy smokes, the universe works in such a bizarre and unpredictable way I don't even try to understand it anymore. Conscious thought probably does have an impact on how the world operates. How or why this is true is waaaaaay over my head. :)


What is he saying at the end of the video?

Scott is saying, "Ok I want to see it" but the video cuts off at "Ok I..." He wanted to see his jump in the screen on the back of the camera. :)

BTW if Scott is cute he owes it all to his mother. :)

Dingo
04-25-2010, 09:36 AM
This story came out today and I thought it was relevant to our discussion of Scoliosis and heredity.

Prostate Cancer: Risk Increases With the Number of Affected Family Members (http://www.sciencedaily.com/releases/2010/04/100423113724.htm)


For a long time now doctors have known that prostate cancer "runs in the family." Men with family members who have been diagnosed with the disease have an elevated risk of developing cancer of the prostate.

Sounds pretty genetic, right?

Well maybe not...

Bloomberg: Prostate Cancer’s Worst Form Linked to Gene-Influencing Virus (http://www.bloomberg.com/apps/news?pid=20601087&sid=a4mbqkGaCrqs)


The virus was present in 23 percent of men with cancer and 4 percent of non-cancerous prostates, the researchers found. The tumors that scored highest on the 10-point Gleason severity scale were more likely to contain the virus, the study found.

This is more evidence that just because a disease hits a family particularly hard doesn't mean it's a genetic disorder. It's easily possible that families who are hit hard by prostate cancer share a genetic susceptability to the environmental damage that triggers the disease. That may turn out to be damage from the XMRV virus discussed in the story.

The fact that most cases of Scoliosis occur sporadically and identical twins aren't 100% concordant for the disease suggests that the environment is a key factor.

Prfbones
05-19-2010, 11:02 AM
AIS: watch the homeobox (HOX) genes that control symmetry. In AIS patients, their mutated product (multiple mutations btw) will be up or down regulated during adolescence with hormone responses. That will be the major contributing factor to severity of scoliosis in adolescents, everything else will just be collateral damage. It's pretty simple really.

It's genetic. No doubt about it.

And just for clarification, Rule Number 1 of bone research: never ever ever ever correlate bird data to humans. Any researcher that does so is way out of their element.

Edit: Sorry Pooka, just read your post. Your doing it right:-)

Pooka1
05-19-2010, 11:12 AM
AIS: watch the homeobox (HOX) genes that control symmetry. In AIS patients, their mutated product will be up or down regulated with adolescent hormone responses. That will be the major contributing factor to severity of scoliosis in adolescents, everything else will just be collateral damage. It's pretty simple really.

It's genetic. No doubt about it.

And just for clarification, Rule Number 1 of bone research: never ever ever ever correlate bird data to humans. Any researcher that does so is way out of their element.

Hey! I mentioned homeobox genes upthread (Post #67). It occurred to me that homeobox genes might be involved based on the constancy worldwide of scoliosis prevalence (similar to the identical twinning rate is constant over the world) and after reading the comment of Ogilvie that identical twinning could be considered a birth defect and as a midline disorder, is not a good experimental model to study AIS.

We have no AIS researchers on this group but we do have a guy who has a doctorate in muscle physiology (skevmic).

We also have a few folkscientists who don't know that they don't know.

Pooka1
05-19-2010, 11:17 AM
Edit: Sorry Pooka, just read your post. Your doing it right:-)

I am in a different field but some things in other fields just fall out along logical lines.

I hope you stay. We need more people trained in a relevant field. At present it is mainly bunnies talking to bunnies except for McIntire. :)

ETA: We do have a few non-bunnies besides McIntire... the lovely and talented Linda Racine who knows many scoli facts, the equally lovely and talented tonibunny who also knows many fact and helps run another scoliosis forum, hdugger who understands the limitations of the literature specifically and research in general, rorher01 who has significant science training, Pnuttro who is a biomedical researcher (non-scoli field), etc.

rohrer01
05-19-2010, 03:36 PM
AIS: watch the homeobox (HOX) genes that control symmetry. In AIS patients, their mutated product (multiple mutations btw) will be up or down regulated during adolescence with hormone responses. That will be the major contributing factor to severity of scoliosis in adolescents, everything else will just be collateral damage. It's pretty simple really.

It's genetic. No doubt about it.

And just for clarification, Rule Number 1 of bone research: never ever ever ever correlate bird data to humans. Any researcher that does so is way out of their element.

Edit: Sorry Pooka, just read your post. Your doing it right:-)

This may be a dumb question, but since you mentioned the surge of hormones at adolescence upregulating or downregulating the mutated gene product, could hormone therapies during adulthood "trigger" the same response and cause the scoliosis to progress?

I ask this question because both of my curves have progressed over the past two years +/-5* and the situation during these two years were:
1. Chiropractic treatment (very intensive bone crunching in the scoliotic regions)
2. My daughter had a baby and lives with us, so more lifting
3. Fertility treatments with several hormones or hormone altering drugs (mulitple shots and pills each cycle)

BTW I am totally convinced that scoliosis is hereditary. After being diagnosed, we have since learned of several affected family members, including my neice and my own daughter. My family "tree" makes for a pretty good pedigree that supports its genetic basis. Ogilvie's research only confirmed what many already knew. :)

Dingo
05-19-2010, 11:29 PM
rohrer01


BTW I am totally convinced that scoliosis is hereditary.

I suppose that somebody has to be on the losing side of every bet. :)

The lifetime risk for type 1 Diabetes is 1 in 100, but if you have one affected family member your risk can be as high as 1 in 10. That's not so different from Scoliosis.

Joslin Diabetes Center (affiliated with Harvard Medical School) (http://www.joslin.org/info/genetics_and_diabetes.html)


If an immediate relative (parent, brother, sister, son or daughter) has type 1 diabetes, one's risk of developing type 1 diabetes is 10 to 20 times the risk of the general population; your risk can go from 1 in 100 to roughly 1 in 10 or possibly higher, depending on which family member has the diabetes and when they developed it.

Sounds pretty genetic right? Not so fast.

Study Of Human Pancreases Links Virus To Cause Of Type 1 Diabetes (http://www.sciencedaily.com/releases/2009/03/090305141639.htm)

In most cases these children probably have a genetic susceptability to a particular virus. Or looked at another way a virus may have evolved a mechanism to overcome the defense offered by a particular gene, or gene combination. It's possible that in the not too distant future a vaccine will eradicate the virus that triggers Type 1 Diabetes.

Nobody knows what causes Scoliosis. The fact that some families are hit particularly hard by AIS means a lot less than many people in the general public might think.

You might find this abstract from 2008 interesting.
Case Study of identical twins discordant for Scoliosis. (http://www.ncbi.nlm.nih.gov/pubmed/18670329)


RESULTS: One of the sisters was considered to be suspicious of suffering from scoliosis. The radiologic evaluation that followed confirmed the existence of adolescent idiopathic scoliosis (left thoracolumbar curve of 32 degrees as measured by the Cobb angle). The clinical and radiologic evaluation of her sibling failed to reveal the existence of any spinal deformity.

CONCLUSION: Adolescent idiopathic scoliosis seems to be a multifactorial skeletal disorder. The role of exercising and heredity in its development remain controversial.

Pooka1
05-20-2010, 05:36 AM
Identical twins may not be a good study model for midline disorders like scoliosis. Comment on that point is conspicuous by its absence in the above post.
Also, identical twin studies with larger numbers of subjects show a very definite genetic component. But those are ignored in favor of a paper that deals with ONE pair of twins. We continually get regurgitated irrelevant comments about other diseases that are shoehorned to fit an ignorant, lay paradigm.

Comment about homeobox genes was conspicuous by its absence in the post immediately above. Its almost like if it doesn't fit into a preconceived notion then it can simply be ignored.

Trying to prove a point, not engaging in trying to disprove competing points and in fact ignoring them out of ignorance, etc. are hallmarks of folk science, folk medicine and folk biology. Textbook case here.

There is no substantive difference between the claim that scoliosis is not primarily a genetic disease and the claim that the earth is flat in terms of amount of evidence.

Pooka1
05-20-2010, 06:09 AM
You might find this abstract from 2008 interesting.
Case Study of identical twins discordant for Scoliosis. (http://www.ncbi.nlm.nih.gov/pubmed/18670329)

The one twin has a left TL curve. Something like 70% IIRC of left curves often have an underlying cause (chiari, syrinx, etc.).

Note how different the conclusion might be if they found 100 identical twin pairs each with ONE having a typical right T curve. There is a reason we don't see that.

No discussion of obvious things like this not to mention the non-obvious ones. This is the danger of dabbling in the literature with no relevant training whatsoever and indeed not understanding the limitations of the literature whatsoever.

rohrer01
05-20-2010, 11:12 AM
rohrer01



I suppose that somebody has to be on the losing side of every bet. :)

The lifetime risk for type 1 Diabetes is 1 in 100, but if you have one affected family member your risk can be as high as 1 in 10. That's not so different from Scoliosis.

Joslin Diabetes Center (affiliated with Harvard Medical School) (http://www.joslin.org/info/genetics_and_diabetes.html)



Sounds pretty genetic right? Not so fast.

Study Of Human Pancreases Links Virus To Cause Of Type 1 Diabetes (http://www.sciencedaily.com/releases/2009/03/090305141639.htm)

In most cases these children probably have a genetic susceptability to a particular virus. Or looked at another way a virus may have evolved a mechanism to overcome the defense offered by a particular gene, or gene combination. It's possible that in the not too distant future a vaccine will eradicate the virus that triggers Type 1 Diabetes.

Nobody knows what causes Scoliosis. The fact that some families are hit particularly hard by AIS means a lot less than many people in the general public might think.

You might find this abstract from 2008 interesting.
Case Study of identical twins discordant for Scoliosis. (http://www.ncbi.nlm.nih.gov/pubmed/18670329)

Haven't we discussed this before....?? I have given you perfectly legitimate reasons for MZ twins not being 100% concordant and so has Pooka1. Why keep beating a dead horse? (Sorry Pooka!)

rohrer01
05-20-2010, 11:13 AM
I think I asked a pretty legitimate "stupid" question about hormone activity and scoliosis progression. I didn't mean to start the same debate over again.

skevimc
05-20-2010, 01:02 PM
This may be a dumb question, but since you mentioned the surge of hormones at adolescence upregulating or downregulating the mutated gene product, could hormone therapies during adulthood "trigger" the same response and cause the scoliosis to progress?

I ask this question because both of my curves have progressed over the past two years +/-5* and the situation during these two years were:
1. Chiropractic treatment (very intensive bone crunching in the scoliotic regions)
2. My daughter had a baby and lives with us, so more lifting
3. Fertility treatments with several hormones or hormone altering drugs (mulitple shots and pills each cycle)




I think I asked a pretty legitimate "stupid" question about hormone activity and scoliosis progression. I didn't mean to start the same debate over again.

Those are good questions. I'd need to learn more about bone metabolism and how hormones affect various components. But certainly, HRT and menopause could affect the curve in someway because of the action it has on bone. Hmm...

On a semi-related note, I just sort of glanced through this thread. I need to look up the scoliscore. I can't watch videos at work. But someone mentioned it about how researchers seem to only focus on adolescence and ignore adults. That is a very important point that does get overlooked. AIS patients go on to become Adult IS patients. Spinal maturity only slows progression to a crawl.

Pooka1
05-20-2010, 01:50 PM
I think I asked a pretty legitimate "stupid" question about hormone activity and scoliosis progression. I didn't mean to start the same debate over again.

I thought that was a super question. I hope the bone doctor takes a whack at it. I suspect you are on to something real.

Dingo
05-20-2010, 02:47 PM
Rohrer01


Haven't we discussed this before....?? I have given you perfectly legitimate reasons for MZ twins not being 100% concordant and so has Pooka1.

To be honest I put Pooka on my ignore list months ago. I see that she is posting but I have no idea what she is saying.

BTW you are correct, gene expression is one theoretical explanation that might explain why MZ twins are discordant. But for quite a few reasons I feel comfortable betting against that hypothesis. It certainly didn't work out that way for Multiple Sclerosis.

April 29th, 2010: MS Study Suggests Key Role of Environmental Factor in the Disease (http://www.sciencedaily.com/releases/2010/04/100428142256.htm)

"Even with the very high resolution at which we sequenced the genomes of our study participants, we did not find evidence for genetic, or epigenetic differences that explained why one sibling developed the disease and the other did not," says the lead author of the study, Sergio Baranzini, PhD, associate adjunct professor of neurology and a member of the Multiple Sclerosis Research Group at University of California, San Francisco.

In most cases heredity is a poor explanation for why children and young adults become sick. When kids get sick something happened to them.

In older people heredity or natural gene expression starts to make more sense.

Pooka1
05-20-2010, 03:06 PM
It certainly didn't work out that way for Multiple Sclerosis.

Non sequitor.

rohrer01
05-20-2010, 04:42 PM
On a semi-related note, I just sort of glanced through this thread. I need to look up the scoliscore. I can't watch videos at work. But someone mentioned it about how researchers seem to only focus on adolescence and ignore adults. That is a very important point that does get overlooked. AIS patients go on to become Adult IS patients. Spinal maturity only slows progression to a crawl.

I'm pretty sure that was me. They treat you very carefully when you are a child, then when you turn 18, you get dumped. I think a scoliscore would be valid to give to anyone who has scoliosis no matter what age. Then give it to all the kids, of whatever age group they decide, who have a strong family history whether they have scoliosis or not (or if they can develop a cost effective versionk, just test all the kids, like they vaccinate all the kids). I think the younger the better, personally. Do it as a preschool screen, then they would likely know already who to watch and who doesn't need watching. It would be a good preventative tool and people like me, who are screened and missed in school, wouldn't get overlooked and therefore treatment could get started earlier.

rohrer01
05-20-2010, 04:51 PM
Rohrer01



To be honest I put Pooka on my ignore list months ago. I see that she is posting but I have no idea what she is saying.



While Pooka1 might be a little bit, okay a lot, edgy (no offense to you Pooka1) when she gets frustrated, she has some very valid things to contribute. She does her research, too, especially when it comes to MZ twinning.

There was something you said about someone has to be on the losing side when I said I believed scoliosis to be genetic. There really are no sides here. If everyone looked at every angle instead of trying to prove the other wrong, we might actually find the culprit. The only losers are the ones with the disease.

twinsmom
05-20-2010, 05:04 PM
Now that I am almost back to sanity, I have been reading through this topic.I find it fascinating. But I have conerns that are more partical than theory at this time. Since the debate is raging, what do you do with our children in terms of intiating them into the great unknown of possibly having their own children deal with AIS? Since my mother had AIS and went to an Orthopod in 1940 and did a form of PT, we all thought she was fine. At 86, the scoliosis is coming back to haunt her. My mother in law had both K and S and was very bad at the end. All of my 4 daughters have some form with the twins the worst. I have it as well. So what is their and my future? What is the best research that is going on? I did a check for clinical trials at NIH but didn't find any good matches for us. Thanks.

Dingo
05-20-2010, 06:13 PM
twinsmom

In my humble opinion our children are the last generation of children in the western world who will suffer from Scoliosis. In another 20 years or so Scoliosis will only exist in the history books.

November 18, 2008: INAUGURATION OF A WORLD-LEADING MUSCULOSKELETAL DISORDERS LABORATORY (http://www.chu-sainte-justine.org/research/nouvelle.aspx?ID_nouvelles=51533&ID_Menu=2546&ID_Page=2546)


With all these advances, Dr. Moreau considers that “we are now, for the first time, in the exceptional position of being able to foresee the eradication of the disease in the very near future with the development of the first drugs within ten years' time.”

Not only do I have strong reason to believe that Scoliosis is not caused by heredity but in the future there will be drugs/gene therapies/etc. to treat and probably cure it. The future is very bright. There is no reason for your children to worry about passing Scoliosis onto their kids.

Dingo
05-20-2010, 06:30 PM
twinsmom

METHOD OF DETERMINING RISK OF SCOLIOSIS (http://www.wipo.int/pctdb/en/wo.jsp?WO=2008119170&IA=CA2008000595&DISPLAY=DESC)

You might find this patent interesting. It pertains to a blood test to detect Scoliosis as well as a medicine to treat it.

Pooka1
05-20-2010, 07:52 PM
While Pooka1 might be a little bit, okay a lot, edgy (no offense to you Pooka1) when she gets frustrated, she has some very valid things to contribute. She does her research, too, especially when it comes to MZ twinning.


Dingo is very clearly NOT interested in anything but his own folk science claims.

rohrer01
05-21-2010, 01:18 AM
twinsmom

METHOD OF DETERMINING RISK OF SCOLIOSIS (http://www.wipo.int/pctdb/en/wo.jsp?WO=2008119170&IA=CA2008000595&DISPLAY=DESC)

You might find this patent interesting. It pertains to a blood test to detect Scoliosis as well as a medicine to treat it.

I do find it interesting. This was an exerpt taken from this article.

[0071] As used herein the terms "likely candidate for developing adolescent idiopathic scoliosis" include children of which a least one parent has adolescent idiopathic scoliosis. Among other factors, age (adolescence), gender and heredity (i.e. born from a mother or father having a scoliosis) are factors that are known to contribute to the risk of developing a scoliosis and are used to a certain degree to assess the risk of developing AIS. In certain subjects, scoliosis develops rapidly over a short period of time to the point of requiring a corrective surgery. Current courses of action available

rohrer01
05-21-2010, 01:34 AM
This was also from the same article:

[0041] Figure 1 presents OPN detection in pinealectomized chicken and corresponding scoliosis. Upper and lower panels illustrates the up regulation of OPN expression detected in paraspinal muscles of pinealectomized chicken developing a scoliosis (S) vs. those remaining unaffected (NS) at the mRNA and protein levels respectively.;

It's my understanding that poultry do not make good study models for humans. I could be wrong. I did appreciate the fact that they did take surgical samples from actual scoliosis patients. This paper seemed to be a conglomeration of information from other papers. It was very long and I admittedly didn't take the time to read it all.

I do give you credit for finding resources for ongoing research. It will be interesting to see what role osteopontin plays in scoliosis. If it is found to play a significant role as this paper asserts, there very well may be therapies developed to treat scoliosis "before" it gets bad or even begins. That's why it is necessary to develop a test that can predict this, thus the work that is being done to develop the scoliscore. Osteopontin activity doesn't negate the fact, even according to the article you posted, that scoliosis has a strong genetic component. Like I said before, we should be hitting this from every angle.

They should also be doing studies on adults. That area of research is sadly lacking.:(

Pooka1
05-21-2010, 05:26 AM
It's my understanding that poultry do not make good study models for humans. I could be wrong.

No you are probably right. The bone researcher said the same thing upthread and she would know... that is her game.

Just because removing a pineal gland from a chicken induces scoliosis doesn't mean that scoliosis is related AT ALL to AIS. Some things seem obvious.

Pooka1
05-21-2010, 05:29 AM
I do find it interesting. This was an exerpt taken from this article.

[0071] As used herein the terms "likely candidate for developing adolescent idiopathic scoliosis" include children of which a least one parent has adolescent idiopathic scoliosis. Among other factors, age (adolescence), gender and heredity (i.e. born from a mother or father having a scoliosis) are factors that are known to contribute to the risk of developing a scoliosis and are used to a certain degree to assess the risk of developing AIS. In certain subjects, scoliosis develops rapidly over a short period of time to the point of requiring a corrective surgery. Current courses of action available

This is not the first time and will not be the last that Dingo posts things that undermine his position without realizing or addressing it. It is obviously correct to post counterarguments and try to explain why they are incorrect but he doesn't realize that he is even doing it so doesn't point it out when it occurs.

mamamax
05-21-2010, 05:33 AM
Just sharing some literature ....




Genetic aspects of adolescent idiopathic scoliosis in a family with multiple affected members: a research article
Published: April 7, 2010 http://www.scoliosisjournal.com/content/5/1/7

The etiology of idiopathic scoliosis remains unknown and different factors have been suggested as causal. Hereditary factors can also determine the etiology of the disease; however, the pattern of inheritance remains unknown.

Methods: Evaluation of 57 family members, distributed over 4 generations of a Brazilian family, with 9 carriers of adolescent idiopathic scoliosis. The proband presented a scoliotic curve of 75 degrees, as determined by the Cobb method. Genomic DNA from family members was genotyped.

Results: Locating a chromosome region linked to adolescent idiopathic scoliosis was not possible in the family studied.

Conclusion: While it was not possible to determine a chromosome region responsible for adolescent idiopathic scoliosis by investigation of genetic linkage using microsatellites markers during analysis of four generations of a Brazilian family with multiple affected members, analysis including other types of genomic variations, like single nucleotide polymorphisms (SNPs) could contribute to the continuity of this study.

And ....

Biopsy material from the skeletal muscle (paraxials) of 21 patients with scoliosis was examined by light and electron microscopy. Virus-like particles, 17 nm in diameter with a crystalline structure, were identified in the skeletal muscle fibres of four patients. Associated changes in the sarcoplasm included swelling of mitochondria, presence of lipid droplets, and vesicular structures. Serological studies and culture for virus isolation gave negative results. An excess of lipid (predominantly in type 1 fibres) was noted in the skeletal muscle of several other cases. The significance of these findings is obscure, but the morphology of the paraxial muscles of patients with scoliosis and controls is currently being investigated in greater detail. http://www.bmj.com/cgi/content/abstract/2/6041/912



I ponder future findings - Maybe this could be a matter of genetic predisposition + familiar/environmental factors .. no one knows beyond scientific shadow of doubt.

twinsmom
05-21-2010, 12:20 PM
Thanks for the interesting links. It seems as if there is a lack of committed and strong push for research. I know with some of the genetic diseases, they use the Amish and Mennonite large extended families for genogram mapping. One family just doesn't cut it in terms of being statistically significant. Probably longitudinal studies need to be created as well. They subjects are out there but once again you have the problem of more clincally orienatated docs having the info but not the time and maybe the interest in clinical research in all that entails... ie storage,data collection, stats person, and of course money. I would reccomend everyone read " The Cure" which came out in the movies with Harison Ford under a different name Medical ?. He was able to find the cure or some of it for his children. He knew and had the money and knowledge base do a research start up company. Also is the medical community liking this as a form of income? Just like Peds like the RH- problem because they would do a proceedure that saved the baby and was lucrative for them. I don't know? But Peds Ortho practices would have less patients. Just something to think about.

flerc
05-21-2010, 12:51 PM
I did not read all the thread. Maybe it have not any sense what I’m saying, but I think that if osteopontin is the cause of scoliosis, then vertebrae wedge in scoliosis must to be terrific as much people says. Someone knows if it is true?

Pooka1
05-21-2010, 01:58 PM
But Peds Ortho practices would have less patients. Just something to think about.

That's fine by me. The really good ones have more patients than they can handle and it is very hard to get an optimal surgery date vis-ŕ-vis school with those guys without booking very far ahead.

Dingo
05-21-2010, 06:34 PM
Mamamax

That's another great study.


Methods: Evaluation of 57 family members, distributed over 4 generations of a Brazilian family, with 9 carriers of adolescent idiopathic scoliosis. The proband presented a scoliotic curve of 75 degrees, as determined by the Cobb method. Genomic DNA from family members was genotyped.


Conclusion: While it was not possible to determine a chromosome region responsible for adolescent idiopathic scoliosis by investigation of genetic linkage using microsatellites markers during analysis of four generations of a Brazilian family with multiple affected members, analysis including other types of genomic variations, like single nucleotide polymorphisms (SNPs) could contribute to the continuity of this study.

9/57 = 15.7%
Even a skeptic like myself has to admit that level of concentration suggests a strong, genetic susceptability. And yet they found nothing.

I hope the scientists involved in this study continue to look at SNPs or other genetic explanations but I doubt they'll find much. They probably mined the richest material first.

Something harmful is spreading through that family, and evidently it's not genes. The CDC (http://www.cdc.gov/) should pay attention to studies like this.

Dingo
05-21-2010, 10:45 PM
twinsmom


It seems as if there is a lack of committed and strong push for research. I know with some of the genetic diseases, they use the Amish and Mennonite large extended families for genogram mapping. One family just doesn't cut it in terms of being statistically significant. Probably longitudinal studies need to be created as well.

You are correct, more research is needed. By the same token scientists still consider the hypothesis that Scoliosis is caused by heredity "controversial". There are other explanations besides heredity. Families and extended families share more than genes.

Exhibit A)
Multiple Sclerosis runs in families. The following comes from the MS page on the Mayo clinic's website (http://www.mayoclinic.com/health/multiple-sclerosis/ds00188/dsection=risk-factors).


The risk of multiple sclerosis is higher for people who have a family history of the disease. For example, if one of your parents or siblings has had multiple sclerosis, you have a 1 to 3 percent chance of developing the disease — as compared with the risk in the general population, which is just a tenth of 1 percent.

Put simply if you have one close family member with MS your risk goes up by more than 1000%. That sounds pretty genetic to me.

But then this comes out...
MS Study Suggests Key Role of Environmental Factor in the Disease (http://www.sciencedaily.com/releases/2010/04/100428142256.htm)


"Even with the very high resolution at which we sequenced the genomes of our study participants, we did not find evidence for genetic, or epigenetic differences that explained why one sibling developed the disease and the other did not," says the lead author of the study, Sergio Baranzini, PhD, associate adjunct professor of neurology and a member of the Multiple Sclerosis Research Group at University of California, San Francisco.

Genes may or may not play a role in MS susceptability. Perhaps in some cases they do, in others not at all. More importantly if MS isn't triggered by heredity what else do families share that could cause this disease? Pathogens.

For a long time scientists have suspected that infection with a common virus is the environmental trigger for MS.
Further Evidence Links Epstein-Barr Virus and Risk of Multiple Sclerosis (http://www.sciencedaily.com/releases/2010/03/100304165900.htm)


"The observation that MS occurred only after EBV is a big step forward," said Alberto Ascherio. "Until now we knew that virtually all MS patients are infected with EBV, but we could not exclude two non-causal explanations for this finding: that EBV infection is a consequence rather than a cause of MS, and that individuals who are EBV negative could be genetically resistant to MS. Both of these explanations are inconsistent with the present findings," said Ascherio.

Now that we know that EBV infection (the virus that causes mononucleosis (http://www.cdc.gov/ncidod/diseases/ebv.htm)) is required to trigger MS what can we do about it?


"The evidence is now sufficiently compelling to justify the allocation of more resources to the development of interventions targeting EBV infection, or the immune response to EBV infection, as these may contribute to MS prevention," he said.

Long story short that means vaccination. Lucky for us one is in clinical trials right now.
Kissing the Epstein-Barr virus goodbye? (http://www.science.org.au/nova/026/026print.htm)

Glandular fever, a common disease in teenagers, is caused by the Epstein-Barr virus. Australian research on the Epstein-Barr virus has led to a glandular fever vaccine being trialled.

If scientists would start looking for the environmental half of Scoliosis instead of the genes that may or may not matter our grandkids would be a lot better off. I read a lot about this kind of thing and Scoliosis does not look like a genetic disease. Scientists need to start looking at the environment. When researchers look at genes it needs to be in the context of how does a particular gene make a child susceptible to the environmental damage that triggers Scoliosis.

twinsmom
05-22-2010, 01:50 PM
Sounds like we are confronting what the makers of the Genome Project have confronted - nothing is clear or simple gene wise and or environmental wise in terms of what actually interacts with genes, chromsones, cells, and organ systems.

I have recently heard that DS, MS, and Parkisnsonism maybe come from outside exposure of a containment/and or autoimmune issue even though DS has a specific gene attached to it.

Go figure. I have a hard time wrapping my mind around an outside force for AIS. It's very counterintuitive to see the problem coming from without and attacking the spine rather than from within. I would really prefer the outside theory. It takes away the guilt at least for me.

It's a very old disease much like Spina Bifida. So you can't readily blame modern day toxins. A virus would work but wouldn't that come out in the lab work? Or since they both are old problems is there something redeeming for our specisis that hasn't been looked for or discovered yet? This might come from those with less severe and no need for treatment type of populations.
Many have postulated that Skiziophrenia comes from a virus with those born in the winter months more likely to develop it. And with certain areas in the world having higher spikes. But still no clear answer.

With another family relative recently dx that bring's my family up to at 7.
Brazil - Midwest USA some sort of gene link must be somewhere. Again I would love to see a Mennoite/Amish like type of study. I think that would really make some headway into at least seeing what shows up and what doesn't. Then from there to other studies with different avenues. Both views expressed on the list have very valid points and both should not be ignored.

Dingo
05-22-2010, 05:08 PM
twinsmom


Many have postulated that Skiziophrenia comes from a virus with those born in the winter months more likely to develop it. And with certain areas in the world having higher spikes. But still no clear answer.

Actually in the case of Schizophrenia/Autism they've made quite a bit of progress. If you google you'll find a ton of stories on Schizophrenia, Autism, immune system and Interleukin 6. Here is one.

Maternal Flu Linked To Schizophrenia, Autism In Child (http://www.sciencedaily.com/releases/2007/10/071016090135.htm)


Surprisingly, the finger of blame does not point at the virus itself. Since influenza infection is generally restricted to the mother's respiratory tract, the team speculated that what acts as the mediator is not the mother's infection per se but something in her immune response to it.


A single, mid-gestation injection of poly(I:C) creates a strong immune response in a pregnant mouse. When her offspring reach adulthood, they display behavioral and tissue abnormalities similar to those seen in schizophrenia in humans.

Dingo
05-22-2010, 05:14 PM
Twinsmom


A virus would work but wouldn't that come out in the lab work?

One problem is that scientists don't know exactly where to look. Scoliosis appears to be a nervous system disorder, not a bone disorder. For reasons that aren't fully understood the nervous system triggers the body to grow incorrectly. We see a spine problem but the "break" is probably in the brain.

Scoliosis may (or may not) be something like Narcolepsy. Narcolepsy is an autoimmune disease in which a tiny bundle of cells in the brain are destroyed by the bodies immune system. When those cells are destroyed the brain loses the ability to properly regulate sleep.

Immune fault 'link' to narcolepsy (http://news.bbc.co.uk/2/hi/health/8025662.stm)


Dr Mignot said: "Narcolepsy is probably the result of a series of unfortunate events, starting with genetic predisposition, involvement of an environmental trigger such as an infection, then T-cell activation, then effects on many other arms of the immune system."

In the case of Scoliosis the brain appears to lose the ability properly regulate Melatonin.
Melatonin Signaling Dysfunction in Adolescent Idiopathic Scoliosis (http://pico.sssup.it/files/allegati/2004_1469.pdf)


Study Design. In vitro assays were performed with bone-forming cells isolated from 41 patients with adolescent idiopathic scoliosis and 17 control patients exhibiting another type of scoliosis or none.

Conclusion. Melatonin signaling is clearly impaired in osteoblasts of all patients with adolescent idiopathic scoliosis tested.

Prfbones
05-24-2010, 09:40 AM
The reason I'm not a scoliosis researcher is there is no funding for serious research. While I was at the NIH in gene therapy research, I made a push for more funding, but apparently at some point in the past, a group of spine surgeons went to Congress and told them there was no need for funding scoliosis research as the disease was able to be cured from surgery. After an event like that, it's difficult to recover from a funding standpoint.

I doubt very much that the AIS gene mutations will be anything like mutations for the adult onset, but I could be wrong. There will still likely be a hormonal component however. I'll have to ponder that question for a bit.

Twin studies offer little of value past the initial concept of a hypothesis. Remember, twins are not clones (no matter what the FBI says). They are only identical at the time of conception. There are a handful of reasons twins do not have exactly the same DNA after that point, males more so than females. But I think everyone is probably familiar with identical twins that are very very different in appearance, either from your community or from the Discovery Channel;) They're not clones.

If this disease were environmental, given the enormity of the population that is affected, one would expect to see large, non-familial pockets where entire communities were affected with the same curve. You'd have epidemiologists from around the world converging on those sites to study the phenomenon. That would happen wherever the environmental factor was strongest. But the disease is pretty homogeneous throughout the population of humanity.

I suspect that the male form of AIS may be fatal in-utero in many cases due to the high fluctuations of hormonal activity during that time. That would account for the percentage discrepancy between males and females as well as the overall greater severity of the disease in males.

For real scoliosis treatments that are in our future, we'll have to wait on gene therapy. Someone will have to fund the gene array sequencing, probably for Miller at Hopkins. Luckily, that's getting cheaper. Don't hold out for gene therapy for our generation though. There's lots of stuff to work through on that end and many countries are being rather negligent with their technique [read: China] and making promises they can't possibly fufill, getting transfected virus into the community (yikes), and other rather dangerous things.


As for multiple sclerosis being genetic, try reading the following article, it's pretty current:

Mol Cell Probes. 2010 May 5. [Epub ahead of print]
The genetics of multiple sclerosis: An update 2010.
Hoffjan S, Akkad DA.

It's a good read. There are over 4,000 other peer-reviewed articles I can point you towards if you're seriously interested in the genetics of that disease. There are also lots and lots of MS gene therapy clinical trials out there- since they're targeting a mutated gene with those, the genetic component is just a given.

Have a great day everyone:)

Prfbones
05-24-2010, 10:01 AM
twinsmom

METHOD OF DETERMINING RISK OF SCOLIOSIS (http://www.wipo.int/pctdb/en/wo.jsp?WO=2008119170&IA=CA2008000595&DISPLAY=DESC)

You might find this patent interesting. It pertains to a blood test to detect Scoliosis as well as a medicine to treat it.


This is a patent application. The problem with patents in medicine is that there's no peer-review, safety studies, or efficacy studies. You can patent anything for any reason, it's your money.

I find their CD44 integrin and HA data fascinating since I have several publications on this protein/GAGs in relation to a leukemia, but it looks like they're just throwing rocks at a problem. They implicate both inhibition AND stimulation in the disease. That's pretty crazy.

Once again though, bird data. It's meaningless for humans.

I will say; however, that is you're married to this and still not believing the genetics of the disease, you'll have to give it up at this point. Everything in this patent points to a genetic component. They're studying message transcription levels of OPN. Message is from DNA. DNA = genetic. CD44 and OPN are both proteins that are encoded by genes in our DNA.

Oh wow, here it is:
"Any amount of a pharmaceutical and/or nutraceutical and/or dietary supplement compositions can be administered to a subject."

Yeah, they're throwing rocks and hoping they'll hit a target and someday be able to sell the patent to a pharma company. Since there's only one article in PUBMED with a loose connection to scoliosis and osteopontin, this is a broad, but little-hope patent. Any dose for any reason. Yikes.

Prfbones
05-24-2010, 10:21 AM
Mamamax

That's another great study.





9/57 = 15.7%
Even a skeptic like myself has to admit that level of concentration suggests a strong, genetic susceptability. And yet they found nothing.

I hope the scientists involved in this study continue to look at SNPs or other genetic explanations but I doubt they'll find much. They probably mined the richest material first.

Something harmful is spreading through that family, and evidently it's not genes. The CDC (http://www.cdc.gov/) should pay attention to studies like this.


SNP = single nucleotide polymorphism. A long word for DNA mutation. i.e. genetic.

The reason they didn't find anything is because since the primary gene hasn't been located, so they don't know where to look yet (they do give a really long list of where others have looked though). The human genome is HUGE and we don't know what everything does yet. Heck, Craig Venter literally just put the first DNA sequence (his own) on the net in 2007. That's really not enough time to have analyzed every single gene for every single disease, much less take into consideration the individual contributions of the SNPs.

There are going to be really big differences in the DNA between these individuals. Not to mention that microsatellite markers were used (bah!). This population was not large enough to find the gene, much less to try and compare the DNA between them and hope to find it by comparing the same DNA (they would have done better to take non-affected village members and subtracting out the different DNA). Not a well-crafted study IMHO as there were no outside or negative controls. Good to see the SNP issue brought up though, I hope they run with it.

Dingo
05-24-2010, 10:35 AM
Prfbones


The reason they didn't find anything is because since the primary gene hasn't been located, so they don't know where to look yet

That's one hypothesis. Another is that Scoliosis, like Multiple Sclerosis (http://www.sciencedaily.com/releases/2010/03/100304165900.htm) and so many other diseases isn't caused by heredity. It's caused by environmental damage. Genes may or may not play a role in susceptability.


While I was at the NIH in gene therapy research, I made a push for more funding...

That's great to hear, you should be extremely knowledgable about genetics.

Can you name a single, childhood disease caused by heredity that looks anything like Scoliosis?
i.e. Common, widespread around the world, potentially fatal, etc. etc.

Pooka1
05-24-2010, 10:35 AM
The reason I'm not a scoliosis researcher is there is no funding for serious research. While I was at the NIH in gene therapy research, I made a push for more funding, but apparently at some point in the past, a group of spine surgeons went to Congress and told them there was no need for funding scoliosis research as the disease was able to be cured from surgery. After an event like that, it's difficult to recover from a funding standpoint.

Remarkable! I almost can't believe that occurred!


Twin studies offer little of value past the initial concept of a hypothesis. Remember, twins are not clones (no matter what the FBI says). They are only identical at the time of conception. There are a handful of reasons twins do not have exactly the same DNA after that point, males more so than females. But I think everyone is probably familiar with identical twins that are very very different in appearance, either from your community or from the Discovery Channel;) They're not clones.

Plenty of people agree with this. I have MZ twins (proof = one chorion) wherein one is allergic to a certain drug class and the other is not. There is a growing realization that epigenetics throws a monkey wrench into the MZ/DZ twin study design.


If this disease were environmental, given the enormity of the population that is affected, one would expect to see large, non-familial pockets where entire communities were affected with the same curve. You'd have epidemiologists from around the world converging on those sites to study the phenomenon. That would happen wherever the environmental factor was strongest. But the disease is pretty homogeneous throughout the population of humanity.

Dingo has been advised of this numerous times to no avail. He didn't address your first post and is not likely going to address anything that upsets his folk science.


I suspect that the male form of AIS may be fatal in-utero in many cases due to the high fluctuations of hormonal activity during that time. That would account for the percentage discrepancy between males and females as well as the overall greater severity of the disease in males.

That's a very interesting suggestion that captures the data.


As for multiple sclerosis being genetic, try reading the following article, it's pretty current:

Mol Cell Probes. 2010 May 5. [Epub ahead of print]
The genetics of multiple sclerosis: An update 2010.
Hoffjan S, Akkad DA.

It's a good read. There are over 4,000 other peer-reviewed articles I can point you towards if you're seriously interested in the genetics of that disease. There are also lots and lots of MS gene therapy clinical trials out there- since they're targeting a mutated gene with those, the genetic component is just a given.

Have a great day everyone:)

That is science. Dingo only deals with folk science. Nice try. :)

Pooka1
05-24-2010, 10:38 AM
Can you name a single, childhood disease caused by heredity that looks anything like Scoliosis? i.e. Common, widespread, potentially fatal, etc. etc.

I posted SEVERAL. Dingo ignores it because it doesn't fit with his folk science.

Also Dingo misses the point entirely that most people who have scolisois probably don't know it. So he mischaracterizes it as "potentially fatal" which is true in only a very few cases of the population that has it.

Pooka1
05-24-2010, 10:39 AM
I find their CD44 integrin and HA data fascinating since I have several publications on this protein/GAGs in relation to a leukemia, but it looks like they're just throwing rocks at a problem. They implicate both inhibition AND stimulation in the disease. That's pretty crazy.

CYA... cover your bases. :D

Pooka1
05-24-2010, 10:40 AM
SNP = single nucleotide polymorphism. A long word for DNA mutation. i.e. genetic.

The reason they didn't find anything is because since the primary gene hasn't been located, so they don't know where to look yet (they do give a really long list of where others have looked though). The human genome is HUGE and we don't know what everything does yet. Heck, Craig Venter literally just put the first DNA sequence (his own) on the net in 2007. That's really not enough time to have analyzed every single gene for every single disease, much less take into consideration the individual contributions of the SNPs.

There are going to be really big differences in the DNA between these individuals. Not to mention that microsatellite markers were used (bah!). This population was not large enough to find the gene, much less to try and compare the DNA between them and hope to find it by comparing the same DNA (they would have done better to take non-affected village members and subtracting out the different DNA). Not a well-crafted study IMHO as there were no outside or negative controls. Good to see the SNP issue brought up though, I hope they run with it.

This will sail over Dingo's head.

Good try though.

Dingo
05-24-2010, 11:09 AM
Prfbones


I suspect that the male form of AIS may be fatal in-utero in many cases due to the high fluctuations of hormonal activity during that time. That would account for the percentage discrepancy between males and females as well as the overall greater severity of the disease in males.

I've never heard that Scoliosis was more severe in males than in females.

This study from 2006 (http://journals.lww.com/spinejournal/pages/articleviewer.aspx?year=2006&issue=08010&article=00010&type=abstract) found that among Juvenile cases both males and females had roughly the same risk of curve progression.

Among adolescents I believe it's generally accepted that females are more likely to suffer from Scoliosis. In addition they have a greater risk of curve progression.

Pooka1
05-24-2010, 11:10 AM
I will say; however, that is you're married to this and still not believing the genetics of the disease, you'll have to give it up at this point. Everything in this patent points to a genetic component. They're studying message transcription levels of OPN. Message is from DNA. DNA = genetic. CD44 and OPN are both proteins that are encoded by genes in our DNA.

Dingo has a bit of a track record of inadvertently posting things that are contradictory because he doesn't understand the work even on a basic level.

Prfbones
05-24-2010, 11:16 AM
Prfbones



That's one hypothesis. Another is that Scoliosis, like Multiple Sclerosis (http://www.sciencedaily.com/releases/2010/03/100304165900.htm) and so many other diseases isn't caused by heredity. It's caused by environmental damage. Genes may or may not play a role in susceptability.



That's great to hear, you should be extremely knowledgable about genetics.

Can you name a single, childhood disease caused by heredity that looks anything like Scoliosis?
i.e. Common, widespread around the world, potentially fatal, etc. etc.

ROFLMAO!!! Of course!!! That's why they test for so many genetic ailments at birth!!! It's because most of them are wide-spread and genetic. Wow.

Pooka1
05-24-2010, 11:17 AM
ROFLMAO!!! Of course!!! That's why they test for so many genetic ailments at birth!!! It's because most of them are wide-spread and genetic. Wow.

Welcome to our world. ;)

Pooka1
05-24-2010, 11:19 AM
We have seen the folkscience claim that scoliosis is too prevalent to be a genetic disease. I have countered that argument already with other reasoning but here is another stab at it.

Here is a list of genetic diseases that have a similar prevalence rate as scoliosis, some many-fold more prevalent than scoliosis.

Scoliosis: ~2 to 4 % worldwide

Otosclerosis: As many as 10% of Caucasians have the condition but most do not get symptoms; about 1 in 100 cases actually lose hearing from otosclerosis

Sickle Cell Anemia: Estimated 1 per 1,000. Hispanic Americans are affected by sickle cell disease in the US

Deuteranopia: About 1% of white males

Protanopia: About 1% of white males

Red-green color blindness: About 10% of males

Of course there are many genetic diseases that are far rarer due to their virulence. Scoliosis, where only about 1 in a 1,000 require fusion and some of these people never get fusion and still live long enough to reproduce, is obviously nowhere near as virulent as the rare genetic disorders. That accounts for the observed incidence rate of 2-4% worldwide; no need for a germ theory of scoliosis.

Here is a short explanation of how prevalence, incidence, etc. have specific meanings...

http://www.bmj.com/epidem/epid.2.html

I think I have been using terms wrongly at times and would need to study this if I continue these ridiculous exchanges.

Last, science advances by trying to disprove false claims. Folkscience "advances" by trying to prove false and, by chance alone, true claims.

Dingo
05-24-2010, 11:20 AM
Prfbones


ROFLMAO!!! Of course!!! That's why they test for so many genetic ailments at birth!!! It's because most of them are wide-spread and genetic. Wow.

You claim to have a PHD and to know a lot about genetics. Like I said before...

Can you name a single, childhood disease caused by heredity that looks anything like Scoliosis?
i.e. Common, widespread around the world, potentially fatal, etc. etc.

Dingo
05-24-2010, 11:29 AM
Prfbones


I suspect that the male form of AIS may be fatal in-utero in many cases due to the high fluctuations of hormonal activity during that time. That would account for the percentage discrepancy between males and females as well as the overall greater severity of the disease in males.

This study from 1998 (http://www.ncbi.nlm.nih.gov/pubmed/9765033) found that girls have a much greater risk of progression. I believe the sample included both juveniles and adolescents.

Are you sure that Scoliosis is more severe in males? Do you have a link to something I can read? That's a really interesting statement from somebody who says they worked at the NIH. I've never read that before.

Prfbones
05-24-2010, 11:38 AM
Prfbones



You claim to have a PHD and to know a lot about genetics. Like I said before...

Can you name a single, childhood disease caused by heredity that looks anything like Scoliosis?
i.e. Common, widespread around the world, potentially fatal, etc. etc.

Like I said, the entire American College of Medical Genetics (ACMG) newborn genetic testing core panel. All of these diseases are common and potentially fatal. The United States has mandated that all newborns born in a hospital in the US are tested for them for those reasons. They are all genetic. You can look them all up for yourself, it's quite an extensive list. But if you've had a child and it was born in a hospital, as a good parent that wanted to be informed of procedures being done to your newborn, I'm sure you've already looked them up.:)

Dingo
05-24-2010, 12:08 PM
Prfbones


Like I said, the entire American College of Medical Genetics (ACMG) newborn genetic testing core panel. All of these diseases are common and potentially fatal.

Wrong again. Before I do my first google search I know that genetic diseases in children are either rare or regional (racial).

But I'll google anyway...

American Academy of Pediatrics: Newborn Screening Fact Sheets (http://aappolicy.aappublications.org/cgi/reprint/pediatrics;118/3/e934.pdf)

biotinidase deficiency (http://ghr.nlm.nih.gov/condition/biotinidase-deficiency) (1 in 60,000 newborns)
congenital adrenal hyperplasia (https://health.google.com/health/ref/Congenital+adrenal+hyperplasia) (1 in 10,000 to 18,000 children are born with congenital adrenal hyperplasia.)
congenital hearing loss (http://genes-r-us.uthscsa.edu/resources/genetics/pdfs/gpc-congenhearing.pdf) (Moderate to profound hearing loss is estimated to occur in approximately 1 out of every 2,000 newborns.) About half caused by genetics
congenital hypothyroidism (http://en.wikipedia.org/wiki/Congenital_hypothyroidism) (1 in 4,000 newborn infants has a severe deficiency of thyroid function) Only some caused by heredity
cystic fibrosis (http://www.wrongdiagnosis.com/c/cf/stats.htm) (Approximately 1 in 3,000 caucasian babies in USA - 1 per 31,000 among Asian Americans)
galactosemia (http://en.wikipedia.org/wiki/Galactosemia) (1 per 60,000 births - much rarer in Japan)
homocystinuria (http://www.wrongdiagnosis.com/h/homocystinuria/prevalence.htm#prevalence_intro) (1 in 200,000)
maple syrup urine disease (http://en.wikipedia.org/wiki/Maple_syrup_urine_disease) (1 out of 180,000 infants)
medium-chain acyl-coenzyme A dehydrogenase deficiency (http://www.wrongdiagnosis.com/m/medium_chain_acyl_coa_dehydrogenase_deficiency/stats.htm) (1 in 16,000 people in the USA)
phenylketonuria (http://en.wikipedia.org/wiki/Phenylketonuria) (1 in 15,000 births but varies by country - 1 in 4,500 in Ireland - 1 in 100,000 in Finland)
sickle cell disease (http://en.wikipedia.org/wiki/Sickle-cell_disease) (In the United States, about 1 in 5,000 black babies have sickle-cell anemia.)
Tyrosinemia (http://ghr.nlm.nih.gov/condition/tyrosinemia) (Type I, 1 person in 100,000 - Type II, 1 person in 250,000)

Pooka1
05-24-2010, 01:53 PM
Prfbones



Wrong again. Before I do my first google search I know that genetic diseases in children are either rare or regional (racial).

But I'll google anyway...

Newborn Screening Fact Sheets (http://aappolicy.aappublications.org/cgi/reprint/pediatrics;118/3/e934.pdf)

biotinidase deficiency (http://ghr.nlm.nih.gov/condition/biotinidase-deficiency) (1 in 60,000 newborns)
congenital adrenal hyperplasia (http://www.wrongdiagnosis.com/c/congenital_adrenal_hyperplasia/prevalence.htm) (affects less than 200,000 people in the US population.)
congenital hearing loss (http://genes-r-us.uthscsa.edu/resources/genetics/pdfs/gpc-congenhearing.pdf) (Moderate to profound hearing loss is estimated to occur in approximately 1 out of every 2000 newborns.) About half caused by genetics
congenital hypothyroidism (http://en.wikipedia.org/wiki/Congenital_hypothyroidism) (1 in 4000 newborn infants has a severe deficiency of thyroid function) Only some caused by heredity
cystic fibrosis (http://www.wrongdiagnosis.com/c/cf/stats.htm) (Approximately 1 in 3,000 caucasian babies in USA - 1 per 31,000 among Asian Americans)
galactosemia (http://en.wikipedia.org/wiki/Galactosemia) (1 per 60,000 births - much rarer in Japan)
homocystinuria (http://www.wrongdiagnosis.com/h/homocystinuria/prevalence.htm#prevalence_intro) (1 in 200,000)
maple syrup urine disease (http://en.wikipedia.org/wiki/Maple_syrup_urine_disease) (1 out of 180,000 infants)
medium-chain acyl-coenzyme A dehydrogenase deficiency (http://www.wrongdiagnosis.com/m/medium_chain_acyl_coa_dehydrogenase_deficiency/stats.htm) (1 in 16,000 people in the USA)
phenylketonuria (http://en.wikipedia.org/wiki/Phenylketonuria) (1 in 15,000 births but varies by country)
sickle cell disease (http://en.wikipedia.org/wiki/Sickle-cell_disease) (In the United States, about 1 in 5,000 black babies have sickle-cell anemia.)

You have to compare the prevalence of these which are all very serious and will prevent a person from reproducing absent intervention to scoliosis wherein even the vast majority of people who reach surgical range still reproduce.

About 1 in a 1,000 people with scoliosis ever reach surgical range. Of these many will not even reach it until after the childbearing years. Maybe a good number for the worldwide percent of people who will reach surgical range who don't reproduce is maybe 1 in 1,000 (just guessing) (assuming surgical range is 50*). So that is one in a million people with the genetic disease called scoliosis will have it prevent them from reproducing. That is a LOWER prevalence rate than all the diseases you mention.

This is not hard. You are avoiding the obvious facts to hold on to your folk science.

The real question is why isn't the prevalence HIGHER given the specific characteristics of scoliosis (i.e., many people never realize they have it, most cases are non-surgical, even most surgical cases likely reproduce at some point, etc. etc. etc.).

Pooka1
05-24-2010, 02:48 PM
http://www.quackwatch.org/01QuackeryRelatedTopics/pseudo.html

This was written by Rory Coker, Ph.D. and I will bullet out the indicators...


The word "pseudo" means fake. The surest way to spot a fake is to know as much as possible about the real thing—in this case, about science itself. Knowing science does not mean simply knowing scientific facts (such as the distance from earth to sun, the age of the earth, the distinction between mammal and reptile, etc.) It means understanding the nature of science—the criteria of evidence, the design of meaningful experiments, the weighing of possibilities, the testing of hypotheses, the establishment of theories, the many aspects of scientific methods that make it possible to draw reliable conclusions about the physical universe.

Because the media bombard us with nonsense, it is useful to consider the earmarks of pseudoscience. The presence of even one of these should arouse great suspicion. On the other hand, material displaying none of these flaws might still be pseudoscience, because its adherents invent new ways to fool themselves every day. Most of the examples in this article are related to my field of physics, but similar beliefs and behavior are associated with iridology, medical astrology, meridian therapy, reflexology, subluxation-based chiropractic, therapeutic touch, and other health-related pseudosciences.


Pseudoscience displays an indifference to facts.


Pseudoscience "research" is invariably sloppy.


Pseudoscience begins with a hypothesis—usually one which is appealing emotionally, and spectacularly implausible—and then looks only for items which appear to support it.


Pseudoscience is indifferent to criteria of valid evidence.


Pseudoscience relies heavily on subjective validation.


Pseudoscience depends on arbitrary conventions of human culture, rather than on unchanging regularities of nature.


Pseudoscience always achieves a reduction to absurdity if pursued far enough.


Pseudoscience always avoids putting its claims to a meaningful test.


Pseudoscience often contradicts itself, even in its own terms.


Pseudoscience deliberately creates mystery where none exists, by omitting crucial information and important details.


Pseudoscience does not progress.


Pseudoscience attempts to persuade with rhetoric, propaganda, and misrepresentation rather than valid evidence (which presumably does not exist).


Pseudoscience argues from ignorance, an elementary fallacy.


Pseudoscience argues from alleged exceptions, errors, anomalies, strange events, and suspect claims—rather than from well-established regularities of nature.


Pseudoscience appeals to false authority, to emotion, sentiment, or distrust of established fact.


Pseudoscience makes extraordinary claims and advances fantastic theories that contradict what is known about nature.


Pseudoscientists invent their own vocabulary in which many terms lack precise or unambiguous definitions, and some have no definition at all.


Pseudoscience appeals to the truth-criteria of scientific methodology while simultaneously denying their validity.


Pseudoscience claims that the phenomena it studies are "jealous."


Pseudoscientific "explanations" tend to be by scenario.


Pseudoscientists often appeal to the ancient human habit of magical thinking.


Pseudoscience relies heavily on anachronistic thinking.

Prfbones
05-24-2010, 03:59 PM
Prfbones



Wrong again. Before I do my first google search I know that genetic diseases in children are either rare or regional (racial).

But I'll google anyway...

American Academy of Pediatrics: Newborn Screening Fact Sheets (http://aappolicy.aappublications.org/cgi/reprint/pediatrics;118/3/e934.pdf)

biotinidase deficiency (http://ghr.nlm.nih.gov/condition/biotinidase-deficiency) (1 in 60,000 newborns)
congenital adrenal hyperplasia (https://health.google.com/health/ref/Congenital+adrenal+hyperplasia) (1 in 10,000 to 18,000 children are born with congenital adrenal hyperplasia.)
congenital hearing loss (http://genes-r-us.uthscsa.edu/resources/genetics/pdfs/gpc-congenhearing.pdf) (Moderate to profound hearing loss is estimated to occur in approximately 1 out of every 2,000 newborns.) About half caused by genetics
congenital hypothyroidism (http://en.wikipedia.org/wiki/Congenital_hypothyroidism) (1 in 4,000 newborn infants has a severe deficiency of thyroid function) Only some caused by heredity
cystic fibrosis (http://www.wrongdiagnosis.com/c/cf/stats.htm) (Approximately 1 in 3,000 caucasian babies in USA - 1 per 31,000 among Asian Americans)
galactosemia (http://en.wikipedia.org/wiki/Galactosemia) (1 per 60,000 births - much rarer in Japan)
homocystinuria (http://www.wrongdiagnosis.com/h/homocystinuria/prevalence.htm#prevalence_intro) (1 in 200,000)
maple syrup urine disease (http://en.wikipedia.org/wiki/Maple_syrup_urine_disease) (1 out of 180,000 infants)
medium-chain acyl-coenzyme A dehydrogenase deficiency (http://www.wrongdiagnosis.com/m/medium_chain_acyl_coa_dehydrogenase_deficiency/stats.htm) (1 in 16,000 people in the USA)
phenylketonuria (http://en.wikipedia.org/wiki/Phenylketonuria) (1 in 15,000 births but varies by country - 1 in 4,500 in Ireland - 1 in 100,000 in Finland)
sickle cell disease (http://en.wikipedia.org/wiki/Sickle-cell_disease) (In the United States, about 1 in 5,000 black babies have sickle-cell anemia.)
Tyrosinemia (http://ghr.nlm.nih.gov/condition/tyrosinemia) (Type I, 1 person in 100,000 - Type II, 1 person in 250,000)

I think your definition of rare is not same as the rest of the medical community. In the US, rare = less than 200,000 people (defined by the NIH).

And just an aside, Google searches aren't research. Many people make this mistake. Try looking on some of the validated databases to answer your more complicated issues. You often have to pay for the information (to avoid copyright infringement), or join a service to do this (as in Lexus-Nexus), but research really begins at that level, not with web browsers. Be careful what you subscribe to with simple web browsing when it comes to medicine. There is a whole lot of bad information out there.

Dingo
05-24-2010, 06:02 PM
Prfbones


I think your definition of rare is not same as the rest of the medical community. In the US, rare = less than 200,000 people (defined by the NIH).

Let's check the definition (http://en.wikipedia.org/wiki/Rare_disease).

In the United States of America, the Rare Disease Act of 2002 defines rare disease strictly according to prevalence, as "any disease or condition that affects less than 200,000 persons in the United States,"[2] or about 1 in 1,500 people.

You are correct. Rare is less than 200,000 people in the USA, or 1 in 1,500 people.

Let's get back to your point professor.

Like I said, the entire American College of Medical Genetics (ACMG) newborn genetic testing core panel. All of these diseases are common and potentially fatal.

Take a look at the newborn screening test again. Every single disease is rare (occurs in less than 1 in 1,500 children). It looks like you were wrong again.

Welcome back to my ignore list PNUTTRO.

skevimc
05-24-2010, 06:42 PM
This is a patent application. The problem with patents in medicine is that there's no peer-review, safety studies, or efficacy studies. You can patent anything for any reason, it's your money.


Yeah, they're throwing rocks and hoping they'll hit a target and someday be able to sell the patent to a pharma company. Since there's only one article in PUBMED with a loose connection to scoliosis and osteopontin, this is a broad, but little-hope patent. Any dose for any reason. Yikes.

This has always bothered me with this group specifically (Moreau). I have seen him present on this blood test since ~2002. They kept it a big secret for many years while claiming that it was a huge discovery. So would present data on mystery protein A - when present showed increased progression and when decreased showed a stable spine (or something like that).

It always rubbed me the wrong way that they potentially had a great discovery but they were intentionally keeping it under wraps because of patent/commercial issues. To be fair, I think they were also concerned with safety and wanting to be sure before they said anything. But it still always seemed a bit strange since that's what research is all about. That is, being unsure of something and so you test it. And let other people test it. And then you get together and discuss it. And then test some more. Instead they did all the testing, got a patent and then released it. I guess we all do it for different reasons.

Dingo
05-24-2010, 06:48 PM
Skevimc


Instead they did all the testing, got a patent and then released it. I guess we all do it for different reasons.

If Dr. Moreau has investors funding his work they certainly won't let him say too much even if he wants to.

Remember this blowup from a few weeks ago? :)

iPhone 4G prototype found on a bar floor? (http://news.cnet.com/8301-13579_3-20002771-37.html)

He can't have something like that happen to his work.

skevimc
05-24-2010, 07:10 PM
Skevimc



If Dr. Moreau has investors funding his work they certainly won't let him say too much even if he wants to.

Remember this blowup from a few weeks ago? :)

iPhone 4G prototype found on a bar floor? (http://news.cnet.com/8301-13579_3-20002771-37.html)

He can't have something like that happen to his work.

Yeah. I never like or want to question someone's motives. Because there is frequently more than meets the eye. I guess we could look at his papers and see who has funded the osteopontin work and see what conflicts of interest he is reporting.

Pooka1
05-24-2010, 09:45 PM
Yeah. I never like or want to question someone's motives. Because there is frequently more than meets the eye. I guess we could look at his papers and see who has funded the osteopontin work and see what conflicts of interest he is reporting.

Just based on that one talk about the top hypothesis for AIS etiology which mentioned two of his ideas, I think Moreau is not viewed as being outside mainstream medicine. But I have to wonder how long that will last given all this stuff. Maybe it is not unusual to tout an unproven idea for years and years. Who knows.

LindaRacine
05-24-2010, 10:12 PM
Welcome to our world. ;)

LOL

And because I need more characters...

LOL again. :)

rohrer01
05-24-2010, 11:51 PM
Dingo, why do you insist that scoliosis is not a genetic disease? I don't understand, considering ALL of the evidence that there is out there, especially that it runs in families.

Yes, I will agree with you that it was most likely "initially" an environmental problem. But what happens is that environmental damage to the germ line, ova and sperm, then become "genetic" because it is a change in the "DNA". These occurances are very, very rare. We would not expect to see it happen over and over again to produce a population of people with scoliosis that we have. If you look at genetic diseases, they probably ALL started that way. So in a sense you are right. It is environmental. But how are you going to go find the person hundreds if not thousands of years ago who sustained the "environmental" damage and study what happened to them. You simply can't.

PrfBones is completely right about doing Google searches. You do have to pay to get into the real literature, at least for more than an abstract. When you choose to completely ignore the overwhelming data that points to genetics in favor of the few feable studies or hypotheses that look at other things (not that there is anything wrong with looking elsewhere), it is misleading to the laypeople out there who think you are an authority on the matter. You're not. Real science doesn't exclude ANY findings that are actually relevant in any way.

This is not a legal venture where we look for precedents. Science doesn't work that way, although it might be nice sometimes if it did. But it doesn't. You come up with a variety of diseases to support your "case", but they are totally unrelated to scoliosis. You would make a great lawyer, but a poor scientist, I'm afraid. I'm not trying to be mean, just honest. Hope no offense is taken.

Dingo
05-24-2010, 11:57 PM
Rohrer01

When you've got some evidence to support your hypothesis please post it.

Until that time the I in AIS stands for Idiopathic. We don't know what causes scoliosis. Scientists consider the notion that it's caused by heredity "controversial".

Pooka1
05-25-2010, 05:39 AM
Rohrer01

When you've got some evidence to support your hypothesis please post it.

Until that time the I in AIS stands for Idiopathic. We don't know what causes scoliosis. Scientists consider the notion that it's caused by heredity "controversial".

You don't have the first clue what scientists consider, think, how they operate, etc. etc. etc. and it shows.

Pooka1
05-25-2010, 05:43 AM
PrfBones is completely right about doing Google searches. You do have to pay to get into the real literature, at least for more than an abstract. When you choose to completely ignore the overwhelming data that points to genetics in favor of the few feable studies or hypotheses that look at other things (not that there is anything wrong with looking elsewhere), it is misleading to the laypeople out there who think you are an authority on the matter. You're not. Real science doesn't exclude ANY findings that are actually relevant in any way.

I posted the hallmarks of pseudoscience on the other thread. I may start listing all the ones associated with everything Dingo says on each of his posts. It's the majority of them, not just a few. It's classical folkscience.


You come up with a variety of diseases to support your "case", but they are totally unrelated to scoliosis. You would make a great lawyer, but a poor scientist, I'm afraid. I'm not trying to be mean, just honest. Hope no offense is taken.

Classic folkscience.

Prfbones
05-26-2010, 11:55 AM
Prfbones



Let's check the definition (http://en.wikipedia.org/wiki/Rare_disease).


You are correct. Rare is less than 200,000 people in the USA, or 1 in 1,500 people.

Let's get back to your point professor.


Take a look at the newborn screening test again. Every single disease is rare (occurs in less than 1 in 1,500 children). It looks like you were wrong again.

Welcome back to my ignore list PNUTTRO.

/sigh.

Reading comprehension for the loss.

Please re-read. Rare, as it is defined by the NIH is not a ratio. You're math is incorrect. Doing math here is incorrect. A rare disease means that less than 200,000 total people in the US have the disease.

As of July of 2009, there are 307,006,550 people in the US. If the disease prevalence is less than 200,000 of that TOTAL population, it's rare. It's not the total population divided by 200,000, that's what we call a ratio. Which is not what rare is.

Wow again. Thank god he's ignoring me. Normally discourse is very good. But wow, when the reading comprehension is so amazingly low...

BTW, hey Linda:) Good to see you again!!!

Prfbones
05-26-2010, 11:57 AM
Rohrer01

When you've got some evidence to support your hypothesis please post it.

Until that time the I in AIS stands for Idiopathic. We don't know what causes scoliosis. Scientists consider the notion that it's caused by heredity "controversial".

So named in the late 1800's. I wonder if the Sun still revolves around the Earth too.

Prfbones
05-26-2010, 12:28 PM
I do want to discuss why I disregard any bone data from birds. I really didn't explain myself here, but it is an interesting bit of science. Birds and cats don't model well for bone.

We have a saying in the bone world that if you throw two cat bones in a closet and shut the door, when you open the door the next day, you'll have a cat. Cats remodel their bone amazingly fast.

Adult humans remodel their entire skeleton about every 2 years or so. That means, the bones you have today were not the bones you had 2 years ago (give or take). Cats do it in a fraction of that time, even if you correct for lifespan.

What is interesting about that fact (the 2 year skeletal turnover) is that something in a scoliosis patient's DNA must send a constant signal to curve even after growth stops. If scoliosis were environmental, when you take that environmental stimulus (or absence of stimulus) away, your spine would grow straight again, because your bones never stop remodeling themselves.

That happens in scurvy. Take Vitamin C away, and your legs curve out over time. Give back the vitamin C and your legs will grow straight again. Completely environmental. But there's not a single peer-reviewed article in PUBMED that discusses spontaneous reversion of an AIS curve to zero without surgical intervention.

But back to bird data:
The two cells that participate the most in bone remodeling are the osteoclasts and the osteoblasts. Blasts lay down the bone and clasts come behind it and eat it up in a constant cycle. At the molecular level, there's woven bone (soft and spongy) and lamellar bone (the strong bones). Woven bone is the first type of bone that begins the process of remodeling after injury or in a baby's "softspot". Lamellar bone is in our long bones and allows us to carry weight.

Bird bones are mostly woven bone. At adulthood in female birds, the osteoblasts switch from making lamellar bone to only making woven bone. This is because in female birds, the woven bone allows better and more rapid access to calcium that is used for making eggs.

There are quite a few other differences, but that's the really big one. It's just not the same type of bone.

Let me know if that's not clear or if I need to expand on any of that.

skevimc
05-26-2010, 01:43 PM
What is interesting about that fact (the 2 year skeletal turnover) is that something in a scoliosis patient's DNA must send a constant signal to curve even after growth stops. If scoliosis were environmental, when you take that environmental stimulus (or absence of stimulus) away, your spine would grow straight again, because your bones never stop remodeling themselves.

That happens in scurvy. Take Vitamin C away, and your legs curve out over time. Give back the vitamin C and your legs will grow straight again. Completely environmental. But there's not a single peer-reviewed article in PUBMED that discusses spontaneous reversion of an AIS curve to zero without surgical intervention.


That's a great example with scurvy and definitely suggests that bones are inclined to form in a particular shape (beyond basic development) even to the point of correcting its shape.

As far as removing the stimulus and spontaneous reversion, I'd want you to expand on that a bit. Because there is a large percentage of scoliosis cases that do revert back to a straight spine. So I'm thinking that you are intending to make a different point, e.g. an established curve with wedged vertebrae.

Stokes' model of vertebral wedging in the rat tail supports the idea that biomechanics plays a big role in progression. So with rapidly remodeling/growing bone, as in puberty, asymmetrical forces applied to the spine could cause wedging absent of a genetic predisposition to grow asymmetrically. Thoughts?




But back to bird data:
The two cells that participate the most in bone remodeling are the osteoclasts and the osteoblasts. Blasts lay down the bone and clasts come behind it and eat it up in a constant cycle. At the molecular level, there's woven bone (soft and spongy) and lamellar bone (the strong bones). Woven bone is the first type of bone that begins the process of remodeling after injury or in a baby's "softspot". Lamellar bone is in our long bones and allows us to carry weight.

Bird bones are mostly woven bone. At adulthood in female birds, the osteoblasts switch from making lamellar bone to only making woven bone. This is because in female birds, the woven bone allows better and more rapid access to calcium that is used for making eggs.

There are quite a few other differences, but that's the really big one. It's just not the same type of bone.

Let me know if that's not clear or if I need to expand on any of that.

Is woven bone different than trabecular bone? Since the vertebral bodies are mostly trabecular bone, it seems like bird spines (at least) would make a decent comparison. Unless the type of trabecular (spongy?) bone is different in birds and humans.


Great to have a bone guy on here. Although apparently you were here before under a different name. Anyway, it's good to talk science.

Prfbones
05-26-2010, 02:54 PM
Woven bone is different than trabecular bone. Woven bone is completely disorganized and random in how it is laid down. It can't hold any weight. It doesn't require any existing components to grow from (like other bone or cartridge), it can grow from scratch. Woven bone is seen in the very young.

Trabecular bone is more of an adult bone structure and it can bare weight and it has some organization. You have trabecular bone, but you don't have woven bone (hopefully).

Lots of lay-texts use these two forms of bone interchangeably, but from a histological perspective, that's not the best thing to do.


And as for wedging vert., yes, that's correct:-)))

:)

P.S. More like a bone-girl. Same name, I just have to travel a lot for my job, so I have long periods of non-connectivity.

rohrer01
05-26-2010, 03:20 PM
Rohrer01

When you've got some evidence to support your hypothesis please post it.

Until that time the I in AIS stands for Idiopathic. We don't know what causes scoliosis. Scientists consider the notion that it's caused by heredity "controversial".

I don't have a hypothessis. I'm just looking at the information available to me, including what you post.

Dingo
05-26-2010, 04:55 PM
prfbones


Please re-read. Rare, as it is defined by the NIH is not a ratio. You're math is incorrect. Doing math here is incorrect. A rare disease means that less than 200,000 total people in the US have the disease.

As of July of 2009, there are 307,006,550 people in the US. If the disease prevalence is less than 200,000 of that TOTAL population, it's rare. It's not the total population divided by 200,000, that's what we call a ratio. Which is not what rare is.

You are splitting hairs PNUTTRO and obviously it doesn't change the math. Every disease on the newborn screening checklist is rare, i.e. less than 200,000 people in the USA. That's the way genetic disease works in children. You were wrong but that's not really a fair description. More accurately you made up something and counted on the fact that nobody would do a simple google search to check your accuracy.

BTW you never posted a source to support this statement.

I suspect that the male form of AIS may be fatal in-utero in many cases due to the high fluctuations of hormonal activity during that time. That would account for the percentage discrepancy between males and females as well as the overall greater severity of the disease in males.

Believe me I'm always happy to learn something new. If that's true post a link. Personally I'm betting you made that up like so many other things you've said over the past year. It's one reason you ultimately ended up on my ignore list. You mix the truth with nonsense which makes it impossible to figure out what's going on.

Dingo
05-26-2010, 08:00 PM
prfbones

Your signature says that you have a Ph.D. in Bone Biology. A few months ago when you went by PNUTTRO you said you were a cancer specialist.

Way to go, I see you are movin' on up! :D

LindaRacine
05-26-2010, 08:20 PM
prfbones

Your signature says that you have a Ph.D. in Bone Biology. A few months ago when you went by PNUTTRO you said you were a cancer specialist.

Way to go, I see you are movin' on up! :D
LOL... yet another fine assumption from Dingo. ;-)

PNUTTRO and PrfBones are indeed two different people.

LindaRacine
05-26-2010, 08:21 PM
BTW, hey Linda:) Good to see you again!!!
You too Alison!

Dingo
05-26-2010, 08:27 PM
LindaRacine


PNUTTRO and PrfBones are indeed two different people.

If you say so. They must be MZ twins seperated at birth.

skevimc
05-26-2010, 11:46 PM
p.s. More like a bone-girl. Same name, i just have to travel a lot for my job, so i have long periods of non-connectivity.


lol... Yet another fine assumption from dingo. ;-)

pnuttro and prfbones are indeed two different people.

oic.. :)

Pooka1
05-27-2010, 05:28 AM
So now we have a bone type and a muscle type!!! We are getting up in the world!

Pnuttro is a cancer researcher of some type. She was also a good all-arounder for helping folks sort out the nonsense from science. I loved her posts and learned more biochem from them. I think she reached her limit though.

Prfbones
05-27-2010, 06:10 AM
prfbones

Your signature says that you have a Ph.D. in Bone Biology. A few months ago when you went by PNUTTRO you said you were a cancer specialist.

Way to go, I see you are movin' on up! :D

Did I say I was a cancer specialist? I have a few publications in a field of leukemia closely related to bone, but I'm by no means a cancer specialist.

Reading comprehension for the loss.

I have no idea who PNUTTRO is and I don't have a twin, but since you like to make assumptions based on no data, I now expect nothing less from your posts. I will tell you though, that I do; however, have a brother that died recently of complications at the age of 49 from his severe untreated scoliosis (we have different mothers, she decided not to treat). So this issue is more than close to my heart.

If people want to get funding for this issue, you'll never get it by arguing about environmental causes. Between the agencies that do that funding, NIH doesn't really specialize in environmental causes and the CDC that does specialize in it has MUCH higher priorities. Maybe you could try the EPA, they have some health assessment groups. If you're serious about pursuing an environmental cause for AIS and getting funding, I'd start there. Let us know how that works out for you.

Dingo
05-27-2010, 08:14 AM
Prfbones


I have no idea who PNUTTRO is and I don't have a twin, but since you like to make assumptions based on no data, I now expect nothing less from your posts.

If you aren't PNUTTRO, sorry that was my mistake.

But back to the point.

I suspect that the male form of AIS may be fatal in-utero in many cases due to the high fluctuations of hormonal activity during that time. That would account for the percentage discrepancy between males and females as well as the overall greater severity of the disease in males.

If you made that up like the stuff you said about the newborn screening test that's fine. But if that's true I'd like to know. If Scoliosis truly is worse in boys... even at a particular age that's interesting. Please post a link.

Prfbones
05-27-2010, 12:09 PM
Go take a look at the data from the 1930's to the mid-1960's, before surgical corrections. These data contain valuable information on the natural progression of scoliosis without surgical fusion to stop the curve from becoming it's 'termainal' curve.

The data we gather today on curve severity can't be used for that purpose because we no longer know how truly severe a curve will get because we have medical interventions.

So go take a look at the old data on PUBMED. I think you'll find it very interesting.

mamamax
05-27-2010, 07:13 PM
Prfbones - I'd be interested in seeing this old data - I'm a collector of sorts. Could you post the links for us? Thanks.

Dingo
05-27-2010, 10:42 PM
Prfbones


Go take a look at the data from the 1930's to the mid-1960's, before surgical corrections. These data contain valuable information on the natural progression of scoliosis without surgical fusion to stop the curve from becoming it's 'termainal' curve.

All the data I see today suggests that Scoliosis is worse among adolescent girls when compared to adolescent boys. However it sounds like you know a lot about this stuff. I'm with Mamamax. Could you post a link to one of the old studies that found that Scoliosis was worse among males? I love to read new things, even if it's from an old study.

Dingo
05-28-2010, 09:58 AM
Prfbones

The Prediction of Curve Progression in Untreated Idiopathic Scoliosis during Growth (http://www.ejbjs.org/cgi/reprint/66/7/1061)


...a study was undertaken at the Twin Cities Scoliosis Center (Fairview Hospital, Minneapolis, and Gillette Children’s Hospital, St. Paul, Minnesota). The information on all juvenile and adolescent patients with idiopathic scoliosis who were seen between 1970 and 1979 was reviewed using the computerized data-base maintained at the Center.

This study of 727 children found that girls progressed at a slightly higher rate than boys. 25% of girls progressed while 18% of boys progressed. However in this sample that difference was considered statistically insignificant. The data is very thorough and there is no mention that boys had more severe curves.

Prfbones
05-28-2010, 11:54 AM
The simple answer is no, I can't post it because it's against the law. You either have to go to a medical library that carries older resources or purchase the copies of the manuscripts from the publishers. Data isn't free, you have to pay for access.

BUT, if memory serves, the Moe textbook actually discusses the data in a chapter of that seminal book. So if you can get a hold of that, you can see some of his meta-analysis on the subject.

hdugger
05-28-2010, 01:48 PM
The simple answer is no, I can't post it because it's against the law. You either have to go to a medical library that carries older resources or purchase the copies of the manuscripts from the publishers. Data isn't free, you have to pay for access.

BUT, if memory serves, the Moe textbook actually discusses the data in a chapter of that seminal book. So if you can get a hold of that, you can see some of his meta-analysis on the subject.

I'm fairly certain fair use laws would permit you to post a paragraph or two, with attribution, within the context of a discussion about the topic.

Some relevant snippets of fair use:

"Section 107 contains a list of the various purposes for which the reproduction of a particular work may be considered "fair", such as criticism, comment, news reporting, teaching, scholarship, and research. Section 107 also sets out four factors to be considered in determining whether or not a particular use is fair:

the purpose and character of the use, including whether such use is of commercial nature or is for nonprofit educational purposes;
the nature of the copyrighted work;
the amount and substantiality of the portion used in relation to the copyrighted work as a whole; and
the effect of the use upon the potential market for or value of the copyrighted work."

And here are some examples

"quotations of excerpts in a review or criticism for purposes of illustration or comment
quotation of short passages in a scholarly or technical work, for illustration or clarification of the author's observations;"

Dingo
05-28-2010, 04:36 PM
Prfbones


The simple answer is no, I can't post it because it's against the law. You either have to go to a medical library that carries older resources or purchase the copies of the manuscripts from the publishers. Data isn't free, you have to pay for access.

The law prohibits you from quoting a few relevant paragraphs and posting the name of the study they came from? Wow! That's some high level stuff. Does the public have access to the abstracts on catalogues like Pubmed or is it even above that? I've heard whispers of research like that. These are the kinds of studies that would blow people's minds.

You and LindaRacine are good friends. You might not want to risk trouble because of your position at the university. However maybe you could forward this information to Linda and she could post it. Even if you can only get us the name of the study through some type of back channel that didn't compromise your job it would be a big help to the parents on this board.

hdugger
05-28-2010, 06:14 PM
Actually, I can locate the Moe text. Can you tell me which chapter? (They're listed here - http://www.amazon.com/Textbook-Scoliosis-Other-Spinal-Deformities/dp/0721655335 - under the "Look Inside This Book" link). I tried looking through the index, but nothing jumped out at me.

Dingo
06-02-2010, 06:23 PM
hdugger

Wow, several days and no response. I think prfbones would like to show us the research but like she said, doing so would put her in serious legal jeopardy.


I can't post it because it's against the law.

Every piece of scientific evidence I've seen points to the fact that Scoliosis is worse among females. However if prfbones says it's worse among males, I'll take her word for it. According to her signature she's a professor and according to LindaRacine she's not PNUTTRO.

That's good enough for me.

PNUTTRO
06-10-2010, 11:47 AM
And I can post anything I like because Dingo has me on his ignore list too.

I think we should make a club.
p

Pooka1
06-10-2010, 11:54 AM
And I can post anything I like because Dingo has me on his ignore list too.

I think we should make a club.
p

I would join except that, "I wouldn't want to belong to any club that would have me as a member." -- Groucho Marx

:D

PNUTTRO
06-10-2010, 12:09 PM
I totally missed the part where Dingo accused Prfbones of being me--that's wonderful.

Pooka1
06-10-2010, 12:23 PM
I totally missed the part where Dingo accused Prfbones of being me--that's wonderful.

Life holds many wonderful little perks.

PNUTTRO
06-10-2010, 02:47 PM
For the record. Regarding the Scolioscore (and many other genetics tests), the test give the clinician and patient some information. At this time, however, it really doesn't change the way that doctors will be treating patients. Newton himself in the video says that you must admit, that you just don't know. I think that unless a genetic test gives you treatment options, it is a lousy genetic test.

The Scolioscore test was initiated using related individuals in Utah. Because they have extensive family histories. I don't know if their sample base has changed over time with the addition of new families. We could be seeing a sample bias here. Not sure--because Axial won't publish anything. If anyone has contrary information, I'd like to see it. So for the patient that scores a 3, it could be that she just doesn't have the same genetic background as the group that was used to establish the test.

I wanted to throw out there that scoliosis is a genetic disorder and there are likely multiple genetic factors involved. There is a relatively new hypothesis that common diseases may be caused by a combination of very rare alleles. Most of our genetic knowledge is now based on the common allele causing rare diseases.

Funny thing that Dingo keeps harping that scoliosis is not genetic, but he likes Dr. Moreau's idea of using blood cells for a functional test of OPN activity of musculature. It isn't a "genetic" test, but it argues that the same protein has similar activities in multiple tissues, so therefore the genetics plays a role.

p

PNUTTRO
06-10-2010, 02:51 PM
Why not do a retrospective study with the scolioscore? Both Ogilvie and Newton said it is a waste of time. I disagree.

There are thousands of patients that progressed past 40 degrees before having surgery. There are thousands of patients that maybe should have braced, but didn't. There are less (harder to find) people that did nothing and nothing major happened. There are those that braced and had successful outcomes. Let's see how this test stands up.

LindaRacine
06-10-2010, 10:48 PM
And I can post anything I like because Dingo has me on his ignore list too.

I think we should make a club.
p

One can only wish.

Prfbones
06-15-2010, 09:04 AM
Had to go OCONUS. 756 emails in my inbox. Be back later:)

P.S. I don't work at a university. I work in national security and law enforcement, so yes, breaking the law is pretty serious business for me.