Kickas.org Forums Ankylosing Spondylitis General Discussion #1 AS Web Support Group discussion with DragonSlayer (DO NOT READ!)

..........and so the dragon tried to breathe fire............but it turned out he was just full of hot air ......(sorry couldn't resist, i'm blaming Alan's corrupting influence for that last one)

I am appalled, utterly appalled, totally completely and utterly appalled at your failure to take this thread seriously.

cripes...

I am surprised you think it rates serious consideration, it seems rather more like a show than a debate, but I shall heed your apalledness and attempt to view this foolsh debate as .....serious... :

For the JROC was armed with the Shield of ERAP1 and it power. A force and depth of knowledge of which the dragon had never encountered nor fashioned a defense for.

Still want a raspberry scone now. BTW what is a preserve ??? LOL ohh a funny English word for jams and jellys

lol

Yes Jam........do you say Jam? Is Jelly, Jam if so what is jelly, is that Jello.......goodness language and food, such confusions they do bring about



Thanks Drizzit; made me smile.

No...no...no, homemade raspberry jam on a Thomas brand fork split English muffin after it has been toasted and slathered in real butter.

Large Shrimp...what does that mean?? are they big or small?...I am so confused.

Are there any humans in this terrestrial epoch, who do not have “culturable Klebsiella” contained within their feces? And You actually believed that?!

In the laboratories of 17 countries the techniques for measuring elevated IgA-Kp (antibodies to Klebsiella) using proper ELISA techniques demonstrated AS patients with active disease in each country had the same antibody elevation: One bacterium and thousands of individuals. There were some of those 17 laboratories that did not achieve their valid results at first, and they required calibration and some refinements to their techniques and laboratory procedures, but they were finally able to substantiate the Ebringer group results.

It is unfortunate that a study was unable to reproduce results that are commonly accepted throughout the world, but their goal was to not find elevated levels of antibodies, so they did not care enough about accuracy. Nor did they care whether their subjects had “active” AS or not. If You think this level of study is rigorous enough for Yourself, that is just fine, but I want a more assiduous and thoughtful approach to my own health issues.



Well, jroc, we here at KickAS have published several Ebringer papers right here on the site, just for reference:

molecular mimicry
Etiopathogenesis of Ankylosing Spondylitis and the Cross-Tolerance Hypothesis
Ankylosing Spondylitis is Caused by Klebsiella…many more…



Not really, as I have already done so in previous posts that You should have by now ferreted out as You seem capable of locating the most arcane and outdated/eclipsed posts to try and embarrass or discredit me. You should already have found it--

But although I would not “care” to elaborate, I shall do so once again for the edification of those few members actually interested (and the delay in this response is mostly because this is no mean exposition, but I have tried to keep it brief enough):

Gender Differences in AS

There are cultural as well as physiological differences between young men and women of the age at which onset of AS would normally occur.

Both groups: Enter the period of greatest susceptibility for the same reason at the same time. If Your doctor does not know this reason, (s)he will not be very useful in helping you to prevent permanent skeletal damage.

Young men: During this period (age 17 through 22) consume food in great quantities, especially convenience foods like starches. They burn calories bulking up and competing in sports. And what they might think was muscle soreness or even torn ligaments or pinched nerve in legs and lower back later turn out to be a chronic condition unrelated to over use or injury.

Young women: In this same age range are more conscious of their weight and usually reduce their consumption of sugars and starches, especially. But another factor is of perhaps more importance and that is the structure of the lymph ducts adjacent to the mesentery. Of course, in girls, these ducts are much longer than in their male counterparts, to accommodate womb expansion.

Molecular mimicry relies upon the fact that the agent provocateur in AS is a specific immunoglobulin, IgA-Kp and this has a half life of about 100 hours.

AS is a disease of lymph and this IgA-Kp (actually in lymph it is a dimer, or 2IgA-Kp), is produced within the lymph nodes, and must travel to the sites of activity through a process of diffusion (Einstein-Brownian motion), sometimes aided by muscle activity, and sometimes retarded by this means. There is nearly twice the volume of lymph in the human body as blood, and at the site of the primary lesion in AS, proposed as the result of molecular mimicry, there are twice as many lymph ducts as blood vessels: The alimentary tract.

Most often, the IgA do not make it through the longer female lymph ducts, in quantities high enough to cause disease, before they expire. There is, thusly, an established threshold that is never breached in some women with AS; these patients often experience activity in their upper backs and limbs before lower “classic” symptom presentation, so common in men. This symptom blurring and flattening of frequency and symptom distribution (platykurtosis), greatly complicates diagnoses in females, as most of us are aware.

Fusion Sites in AS

The process of inflammation in AS can sometimes lead to bony fusion, or bridging osteophytes called syndesmophytes. If AS will be characterized as a disease process that is one result of many episodes of KRA (Klebsiella Reactive Arthritis), through the basic process of molecular mimicry, then the disease can be studied (and even treated) with far greater success.

In this process, the IgA-Kp will bind with Osp (Outer surface protein) of B27-rich cells (collagens I, III, IV, and V), and two adjacent IgA-Kp, will trigger a complementary cascade, signaling the release of myriad necrotic cytokines that help disassemble dead cells. The inflammation is due to the perfusion in lymph of cellular bits, some of which are left behind, just as cinders after a fire. These are often calcium-rich immune components and also change the synovial chemistry to leach local calcium from local bone. The resultant fusion is much weaker than normal bone, lacking tension structures and matrix, marrow, and other key factors.

There are, of course many site variations and some kinds of joints will not fuse, especially in more active individuals, and some joints will fuse at differing rates, subject to many conditions like local mass-transport and basic reaction kinetics. There is a period of up to two years between "fibrosis" or thickening of the synovial fluids and ultimate fusion.

[And as a side-note, I regret that this is the level of my own understanding; I only offer this as a humble response to Your questions. However, I believe that molecular mimicry can adequately answer every such challenge, despite my own level of understanding and inability to communicate adequately].




Administration whacked my tail, perhaps because, despite Your “Do Not Read” suggestion, it seems other people were actually reading this, too.



Yes, of course: I herein and hereby speak with the same authority as You; …or did You simply appoint Your own self as spokesman for “the scientific community?” Is that EVERY scientist? Because I asked several scientist friends, and they had never even heard of jroc (must have used Your nom de plume).



And I don’t know what “bluff” You are referring to (neither does the good professor, in all probability). But this brings up another issue: Have You ever encountered any fact that You would have been too embarrassed to misrepresent?



I stagger under the influence of such a mental image, and bewildered as to why You would wish to punish me for promoting Ebringer’s valid work and opinions all along! I think You are overexposed already. But I could not offer any scene so “precious.” If You win, I’ll hire a male escort to play Twister with You, and tattoo on my backside: “Ebringer was wrong!!” with a tear emanating...ugh...from my lumbar spine.

TTFN,
John

Yes a good one jeff, rather like

'oh that large shrimp was terribly good.........'

yes there are and yes i did as i actually read the studies.

1978 - Roland and Alan Ebringer - "Of the 144 intervals asessed as active disease, 90 (63 %) were found to have at least one positive culture for klebsiella" - http://ard.bmj.com/content/37/2/146

"Klebsiella was isolated from 14 of 26 (54%) patients with either active ankylosing spondylitis or active Reiter's syndrome" - http://rheumatology.oxfordjournals.org/content/XXII/suppl_2/85.abstract

1981 - "Thirty-two patients provided 87 faecal specimens, of which 26 (30%) gave positive cultures for Klebsiella spp." - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1000838/

"Of those assessed, 24 out of 89 AS patients (27%) and 26 out of 82 RA patients (32%) had klebsiella in the faeces." - http://ard.highwire.org/content/39/1/37.abstract

these numbers are a far cry from the 100% that you would expect to see if all cases of AS were caused by klebsiella.


these results are mean (average) IgA-Kp levels of AS patients and by the sounds of it they didn't find elevated levels until they used "calibrations and refinements" to manipulate their results. on average AS patients have higher IgA-Kp than controls but it's still a minority of AS patients that have the higher IgA-Kp levels that increase the average level. "Increased antibody levels in ankylosing spondylitis patients were most often observed against K. pneumoniae (in 35 out of 99 patients)" - http://www.ncbi.nlm.nih.gov.ezproxy.massey.ac.nz/pmc/articles/pmc1535427/

the percentage of patients with raised IgA-Kp seem to be about the same percentage as those with culturable Kp, around 30-50%. this is what you would expect in patients with increased gut permeability. the numbers are not even remotely close to the 100% that you'd need if you're going to argue that all AS is caused by klebsiella.

Ebringer says things like "In most of these studies, no elevations of antibodies against other microbial agents were detected" but this is not true. in the above study they also had elevated antibodies to yersinia and they usually only test for a few species. to put this in context, if 6 species are tested out of the 500-1000 species in the gut then they are testing 0.8% of gut bacteria species. and even when they do this they find elevated antibodies to many other species as well as klebsiella. this is why real researchers say things like "Elevated levels of specific antibodies to a range of Enterobacteriaceae have been demonstrated in AS but this finding is likely to reflect increased intestinal permeability rather than imply a causative role for these organisms."

Ebringer says that "Any theory trying to answer the question of what causes AS must provide an explanation for the specific facts known about these diseases: 1. The male/female ratio in AS is 3/1" and yet in his 2007 magnum opus 'AS is linked to klebsiella: the evidence' the best he can come up with is "Increased prevalence of AS in young adult males could be explained by higher starch intake and hence an increased likelihood of Klebsiella growth in the gut" and can't cite any references because he doesn't have an ounce of evidence because he just made it up. why didn't you tell him about the lymph stuff! he could of used that. it sounds almost plausible. and in his 2011 AS paper on 'popper sequences' (more on this later) he says "post-pubertal hormonally-induced muscle mass leads to increased starch consumption and onset of AS". i thought your theory about a drop in growth hormone levels after puberty was a much better explanation. why did you never tell Ebringer about it?! he was clutching at straws when his chief disciple had a far better explanation for age of onset and gender differences. i like your explanation of the fusing process. nice work, however my specific question was "why do some fuse and some don't?". as it's not very relevant to this discussion anyway i'm going to overlook that minutiae and give full marks. well done.


thankyou for admitting that you just made up the idea that the scientific community agrees with Ebringer 3:1. i am not a spokesman for the scientific community. the reason i say things like the scientific community don't takes Ebringer's ideas seriously is because i have read hundreds of papers on AS and none of them agree with Ebringer's klebsiella hypothesis or give it more than a brief mention as they've moved onto more promising areas of investigation.



calling his bluff means saying: hey, you're hypothesis is clearly false. one example of this was the paper AS is not caused by klebsiella. other scientists in the field haven't bothered to do this, instead they can see that the evidence doesn't support it and have moved on. it is assumed that the scientist will figure it out soon enough and admit that they were wrong and move on as well. to quote the 'crank' article from earlier in the thread - "Admitting you're wrong in science is not a big deal because scientists are wrong all the time!", especially with speculative hypotheses such as Ebringer's. but he still hasn't figured it out despite mountains of evidence staring him in the face. "Scientists are supposed to be willing to give up cherished hypotheses if that's what evidence and experimental results show. Of course, the difficulty in doing so tends to be proportional to both the length of time the hypothesis has been cherished and the intensity of attachment." the first paper on AS fecal klebsiella by Ebringer came out in 1978, and he spent the next decade coming up with the b27 molecular mimicry hypothesis which culminated in his 1992 paper 'AS is caused by klebsiella'. that's 14 years spent thinking about klebsiella and trying to link it to AS! that's a long time to have wasted so i can understand why he was reluctant to ditch it.

Ebringer loves to wax lyrical about Karl Popper and the philosophy of science. his last 2 papers - one on AS-klebsiella and one on RA-proteus use 'popper sequences' to try and implicate these bacteria in the diseases. but what would Karl Popper really think about Ebringer's science? i think we can gather some clues by examining his paper science, pseudo-science, and falsifiability

Popper states that "It is easy to obtain confirmations, or verifications, for nearly every theory—if we look for confirmations." Ebringer seems to have misunderstood what he was saying as he only ever looks for confirmation of klebsiella in stools, klebsiella Iga, and klebsiella binding to b27, and "calibrates" techniques to get the desired results whilst ignoring the mountain of contrary data. Popper would not be impressed as he thinks that "Every genuine test of a theory is an attempt to falsify it, or to refute it."

Popper also states "Every good scientific theory is a prohibition: it forbids certain things to happen. The more a theory forbids, the better it is." Ebringer took this message on board when he states "if removal of Klebsiella microbes and reduction in anti-Klebsiella antibodies did not arrest the clinical progression of the disease, then this would be a critical Popperian test of the theory and disprove the hypothesis that "AS is caused by Klebsiella." now i think he's got ahead of himself already there. if klebsiella microbes are not present in the first place then they cannot be reduced. to use Popper's favourite analogy, Ebringer's theory that all AS is caused by klebsiella is like saying that all swans are white. one only has to find a black swan to falsify the theory. a black swan in this case would be a patient with AS who has no fecal klebsiella or no antibodies to klebsiella. according to Ebringer's own 1978 study, 37% of patients are black swans as they have no klebsiella in stool, even when tested multiple times over long periods. modern studies have found closer to 70% of patients with no fecal klebsiella. the same with IgA. there are whole flocks of black swans flying around but he seems to be oblivious. it is so easily falsified it is bordering on the absurd.

once again Popper proves enlightening - "Some genuinely testable theories, when found to be false, are still upheld by their admirers — for example by introducing ad hoc some auxiliary assumption, or by re-interpreting the theory ad hoc in such a way that it escapes refutation. Such a procedure is always possible, but it rescues the theory from refutation only at the price of destroying, or at least lowering, its scientific status." Ebringer has lowered the scientific status of his theory to a new dimension by not making any attempt to falsify it and is now ironically using Poppers philosophy of science to construct his 'popper sequences' which as far as i can tell he invented himself and have never been used by anyone else in the history of medical science. this type of "ad hoc reinterpretation" is exactly what Popper said that would happen when people can't admit that they are wrong.

here is an extract from Ebringer's paper 'Rheumatoid arthritis is caused by Proteus : the molecular mimicry theory and Karl Popper' - "Popper proposed that a scientific theory could not be proved but could be disproved or falsified. “It must be possible for a scientific system to be refuted by experience”(1). The theory that “All tigers are carnivorous” is refuted or falsified by the observation of one vegetarian tiger. An interesting problem in science and medicine is the cause or origin of the disabling and crippling disease “rheumatoid arthritis” (RA). RA is a disease of the musculo-skeletal system, predominantly of the small joints of the hands and feet, affecting women 3-4 times more frequently than men. There are conservatively over 20 million individuals in the world affected by RA or its early stages when a precise diagnosis is not possible. It is proposed to apply Popper’s method to find a solution to the scientific problem as to what is the cause of RA."

once again Ebringer fails to realise that there is no need as KA's very own Wendy took less than 5 minutes using her own 'Popperian' logic in this thread to find plenty of vegetarian tigers and black swans. Wendy says "Being me, I immediately had to start researching this bacteria. I found a research project from 1998 that suggests proteus mirabilis as a trigger for RA...What interests me is that only 33% of the RA patients had evidence of infection by proteus mirabilis so there may be multiple possible triggers for RA and maybe for all auto-immune diseases." spot on Wendy, you got it! Ebringer unfortunately doesn't get it and the mental gymanstics that he engages in to try and avoid reality are comical.

more from the RA paper -
"It is proposed to apply Popper’s method to find a solution to the scientific problem as to what is the cause of RA. Molecular mimicry has been suggested as a possible model and it will be examined using Popper’s ideas and the principle of parsimony enshrined in Ockham’s razor. The logical basis of scientific research is the method of bold conjectures and of attempted refutations. The process can be described by the following oversimplified schema (Figure 1). We start from some “problem” (P1) proceed to a tentative solution or “tentative theory” (TT) which may be partly or wholly mistaken. The theory will be subject to “error elimination” (EE) which may consist of critical discussion or experimental tests. At any rate new problems will arise (P2) which may require further solutions. At every step, new unintended facts, new unexpected problems will occur which will increase our knowledge of the subject.

The second problem (P2) is in general different from the first, it is the result of the new situation which has arisen, in part, because of the tentative theories (TT) or tentative solutions which had been tried out and the error elimination (EE) which controls them. One could label this schema a “Popper sequence”. As new problems arise, new “Popper sequences” can be generated which require further experimental verification. The task of science is to explain as many facts as possible, in other words to get at the truth. However we are not simply looking for any truth, we are looking for interesting and enlightening truth. We are after theories which offer solutions to interesting problems. If at all possible we are after “deep” theories. We are after theories which have an extensive explanatory power that may lead to even useful applications.

If the cause of RA could be found, then it would have immense repercussions, since this information could be incorporated in the therapy of this crippling disease. A cursory examination of rheumatology books will show that the cause of RA is unknown. In a famous passage Karl Popper offers a way as how to handle this situation: “Assume a young scientist meets a problem which he does not understand. What can he do? I suggest that even though he does not understand the problem, he can try to solve it and criticise his solution. Since he does not understand the problem, his solution will be a failure, a fact which will be brought out by criticism. In this way, a first step will be made towards pinpointing where the difficulty lies. This means precisely, that a first step will be made towards understanding the problem, for a problem is a difficulty and understanding a problem consists in finding out where the difficulty lies. And this can only be done by finding out why certain solutions do not work. So we learn to understand a problem by trying to solve it and by failing. When we have failed a hundred times, we may become even experts with respect to this particular problem. That is, if anybody proposes a solution we may see at once, whether there is any prospect of success for this proposal or the proposal will fail because of the difficulties which we know only too well from our own past failures”.

The question “What kind of explanation may be satisfactory ?” leads to the reply, an explanation in terms of testable theories and falsifiable universal laws and critical conditions. An explanation of this kind will be the more satisfactory, the more highly testable these laws are thereby proceeding to better theories. Each new theory (T2) will contain the previous theory (T1) as an approximation. For instance Newton’s theory of planetary motion was a better approximation to Galileo’s theories, which in turn were a better approximation of the theories of Copernicus. Thus a theory which leads to the discovery of new facts has changed the debate about the original problem.

...The identification of Proteus as the cause of RA, clearly explains why this disease occurs more frequently in women, since they suffer from an increased incidence of urinary tract infections. It also accounts, using Ockham’s razor ... "

in addition to incomprehensible ramblings about Popper, waxing lyrical about Ockham's razor is another classic psudoscience tactic. in order for Ebringer to keep insisting his theories are right, it requires that he ignores all the data that inconveniently contradicts his theories like the majority of people with AS with no klebsiella and the majority of people with RA without proteus infections - "By rejecting a datum, based on the idea that it introduces plurality, one effectively ensures that no data will ever be found which produces a competing construct. You will in effect prove only what you are looking for, regardless of whether or not you use the scientific method from that point onward. No competing idea can ever be formulated because outlier data is continuously discarded one datum at a time." here's John on the topic - "when people reject Occam's Razor--ANYTHING becomes possible. It is the subjugation of the intellect by Liberal "science" that allows us a way out of the TYRANNICAL TRUTH. But REAL SCIENCE begins with the most liberal (small "L") philosophy possible--ACCEPT ALL THEORIES until they can be disproven and discarded." i guess we can now discard the theory that all cases of AS are caused by klebsiella.

reading between the lines of the conclusion of the RA paper is highly informative. Ebringer says - "In science, we are trying to get closer to the truth but in medicine, the results of our investigations should help the patient." Ebringer has a sincere desire to help patients and come up with practical solutions. for example in this Ebringer interview on the topic of RA - "While other rheumatologists deal with the symptoms of this disease, Ebringer finds that its female sufferers can be helped if they control their susceptibility to cystitis simply by drinking a lot of fluids." if you enjoy reading insane ramblings about 'popper sequences', want to believe that AS and RA are caused by bacteria that can't possibly be responsible, and like to pretend that severe arthritic diseases are best treated simply by drinking more fluids or cutting back on starch then Ebringer is your guy. if you are interested in good science and finding out the truth about the cause of your disease then Ebringer is best avoided.

i would read this thread with more pleasure if personal attacks would not be involved.

@jroc.
you cannot claim objectivity if you keep like this. you have scored a lot, your arguments are well built, but...there's a big but...