Has Anyone Tried Or Been On Biologics?

[RichGotsPots]

http://www.alexanderinjury.com/blog/rituxan-causes-deadly-brain-infections/

"DrugLib.com compiles statistics and information on the benefits and dangers of prescription medications attributed 113 wrongful deaths to Rituxan during the calendar year 2007. PML was just one of the causes of death associated with Rituxan, as well as personal injuries: blindness, lung disease, and gastrointestinal ulcers"

"In May 2009, a study from the Feinberg School of Medicine at Northwestern University linked Rituxan to PML. The study identified 57 cases of PML, and 51 of those patients died."

Jangle- Where did you get your statistics from?

btwn even a Vaccine is considered a Biologic..

[dsdmom]

My main concerns with rituximab is that is is being prescribed by doctors who often have an incomplete understanding of the etiologies that they are using it to treat, and ofcourse no one has a clue why it helps the nebulous and ill-defined entity called CFS - an illness based on 'subjective symptoms' rather than objective measurements and a disease that mimics dysautonomias in some ways.

What doctors are you referring to here?

[jangle]

My main concerns with rituximab is that is is being prescribed by doctors who often have an incomplete understanding of the etiologies that they are using it to treat, and ofcourse no one has a clue why it helps the nebulous and ill-defined entity called CFS - an illness based on 'subjective symptoms' rather than objective measurements and a disease that mimics dysautonomias in some ways.

As an example, Vanderbilt found that all the POTS patients they found who also had CFS and those with just POTS were indistinguishable from each other other than increased sympathetic activity in the POTS/CFS group. So its all just speculation - nearly all of the CFS research provides conflicting and confounding results.

I dont think rituximab is an overly scary drug but all biological immuno-supressants have obvious risks. But if the argument is that it would help cytokine regulation then its a long shot since it works on b cells which are actual plasma-based immune cells rather than cytokines.

As Issie has suggested there are many foods that may effect histone regulation of epigenetic gene expression but since our understanding of non methylated regulation of genes is very infantile (from research) its impossible to determine how some dietary substances may effect the gene one way or the other.

Rich - I think your the only one talking about gene therapy and Im not sure what you mean by 'so many levels' and autoimmune issues? Autoimmune v cytokine expression abnormalities - quite different.

Sounds like POTS research. There's articles saying our cerebral autoregulation is preserved, then there are articles that say it isn't. There are articles that say angiotensin ii is elevated, but only in a subset of patients. Then there are articles that say our autonomic nervous system is dysfunctional, and then there are articles that say it is normal and we only have low stroke volume.

The only finding I'm willing to attach myself to anymore is the NET finding, because another study showed that POTS can be induced in normal volunteers by inhibiting their NET.

[RichGotsPots]

Rama good points mate. And don't worry we are talking about the something... .

Jangles- pots has so many symptoms that's why it's a syndrome so what ever study says they can induce pots symptom, I don't believe it. What exactly are the symptoms? We all have a mix of tons of symptoms. It's not the same as saying they can induce a heart attack which has very little clinically observed symptoms. I think you are giving that study to much weight. I do however think they probably induced a had full of the same symptoms, but again pheo probably has the same symptoms they induced bet blocking NET. So I think all they proved was NE plays a role, which I think most pots hyper research already alludes to. Maybe this study does go a little further. I just don't think it's a simple matter of the levels we have. It could be a new found sensitivity. I wish there was a way to test to a synaptic chain reaction to neurotransmitters or something like that. For example NE is synthesized by Dopamine yet dopamine levels aren't at higher abnormal level, so that probably means the dysfuction isn't at that stage, but what about the stage after NE is transmitted? NE is most potent acting on a1 receptors? A1 receptors are types of g-protein receptors and Dyfuction of these g-protein receptors have been linked to diabetes, allergies, cardiovascular defects, depression and certain forms of cancer...

One of the best A1 meds I found is Prozosin http://en.wikipedia.org/wiki/Prazosin they use it to treat high BP, anxiety, PTSD, and panic disorder. But here is the problem with a straight of NET/NE issues, NE straight up increase BP by vasoconstriction, some of us have dysfuctioning BP, sometimes it's high sometimes it's low and sometimes it's normal. By decreasing NE by using an antagonist med this causes a lowering a BP, but what happens when my BP is already lowered when I walk. If NE is higher when I stand and walk then my BP should be higher when I do both as well, why does my BP drop when I walk or stand for more than 10 minutes, it can't only be do to NE is my point. We would have a better answer if they did test NE levels at least 6x or so in a tilt and during exercise. The they could say, ahah I can clearly see how everyone's levels are dysfuctioning by going up then dropping and then they can connect the dots..

If infect everyone has different degrees of NET issues or the NET issues are happening in different areas of the body at different levels then wouldn't we need targeted treatments to those areas? More research is needed before I think the docs can target everyone across the spectrum.... That's why I caution you. 1 in 20 btw is not rare, 1 in 100,000 is rare. Would you take Tylenol is 1 in 20 people died form 1 treatment of it? We would have a lot of dead people in just one day... 1 in 2000 is still risky to me, it means if 2 million people took it 100 would die from it.... Maybe some chemo meds have that same risk but what people on chemo are facing is nearly certain death if they don't try it where as I don't think we are in the same boat... I'd have to be 100% sure this was going to cure my pots for life... Then maybe I'd give it shot...

[jangle]

Rama good points mate. And don't worry we are talking about the something... .

Jangles- pots has so many symptoms that's why it's a syndrome so what ever study says they can induce pots symptom, I don't believe it. What exactly are the symptoms? We all have a mix of tons of symptoms. It's not the same as saying they can induce a heart attack which has very little clinically observed symptoms. I think you are giving that study to much weight. I do however think they probably induced a had full of the same symptoms, but again pheo probably has the same symptoms they induced bet blocking NET. So I think all they proved was NE plays a role, which I think most pots hyper research already alludes to. Maybe this study does go a little further. I just don't think it's a simple matter of the levels we have. It could be a new found sensitivity. I wish there was a way to test to a synaptic chain reaction to neurotransmitters or something like that. For example NE is synthesized by Dopamine yet dopamine levels aren't at higher abnormal level, so that probably means the dysfuction isn't at that stage, but what about the stage after NE is transmitted? NE is most potent acting on a1 receptors? A1 receptors are types of g-protein receptors and Dyfuction of these g-protein receptors have been linked to diabetes, allergies, cardiovascular defects, depression and certain forms of cancer...

One of the best A1 meds I found is Prozosin http://en.wikipedia.org/wiki/Prazosin they use it to treat high BP, anxiety, PTSD, and panic disorder. But here is the problem with a straight of NET/NE issues, NE straight up increase BP by vasoconstriction, some of us have dysfuctioning BP, sometimes it's high sometimes it's low and sometimes it's normal. By decreasing NE by using an antagonist med this causes a lowering a BP, but what happens when my BP is already lowered when I walk. If NE is higher when I stand and walk then my BP should be higher when I do both as well, why does my BP drop when I walk or stand for more than 10 minutes, it can't only be do to NE is my point. We would have a better answer if they did test NE levels at least 6x or so in a tilt and during exercise. The they could say, ahah I can clearly see how everyone's levels are dysfuctioning by going up then dropping and then they can connect the dots..

If infect everyone has different degrees of NET issues or the NET issues are happening in different areas of the body at different levels then wouldn't we need targeted treatments to those areas? More research is needed before I think the docs can target everyone across the spectrum.... That's why I caution you. 1 in 20 btw is not rare, 1 in 100,000 is rare. Would you take Tylenol is 1 in 20 people died form 1 treatment of it? We would have a lot of dead people in just one day... 1 in 2000 is still risky to me, it means if 2 million people took it 100 would die from it.... Maybe some chemo meds have that same risk but what people on chemo are facing is nearly certain death if they don't try it where as I don't think we are in the same boat... I'd have to be 100% sure this was going to cure my pots for life... Then maybe I'd give it shot...

I do think that the base abnormality of POTS is NET deficiency. The subsets are probably explained by additional confounding factors associated with NET deficiency. Some have MCAD, Mito, and/or EDS in addition to other yet to be determined that gives additional factors. Other autoimmune illnesses follow a similar pattern with different people under the same classification experiencing different symptoms yet having relatively the same underlying pathphysiology +/- some other unknown confounding factors. For instance some with lupus have anti phospholipid antibodies which explain the CNS symptoms, whereas others with Lupus have no CNS involvement, but both patients are still said to have Lupus from the underyling common autoantibodies and criteria they share.

I guess it depends on your own individual threshold. For me, 1 in 4 is kinda rare. 1 in 10 virtually never happens, and 1 in 20 is basically like mini lottery odds, but when considering life or death I probably wouldn't do something willingly if I knew there was a 1 in 20 chance of me dying.

1 in 2000 though is two orders of magnitude more rare. That's not something I would even worry about.

[RichGotsPots]

Jangle I think you are looking at the 1 in 2000 odds like gaming odds or like insurance type of odd. These odds are based on past actual deaths which means almost with certainty they will happen in the future. But in gambling it's not certain at all. For example Pepsi one time had a billion dollar under the cap contest and warren buffets reinsurance company insured the contest for about 10 million because the odds were like 1 in 100 million chance someone would win. No one won, see so those are odd that no one might ever collect, in medical odds people have already died and that's not including disabled or near death... The only thing that is for sure is if you don't take them you won't be that 1 in 2000 for sure.. To put it on more way, if 1 in 2000 kids were born with a heart defect would you call that heart defect rare? In a small town with 20000 people 10 children every year would have it and after 10 years worth 100 children in the town 10 and under would have it...

Lupus isn't a syndrome, there are many types of lupus and with every illness there are mild to severe spectrum even with a cold? There are many types of syndromes, aids is a type of syndrome, parkinsonian is a syndrome, Down is a syndrome... The problem with NET as a base is that the researchers looked at the NET gene that they found with the same abnormalities in the twin girls and they tested 40 other patients and didn't find the same abnormality. I'm not saying its not there, I'm just saying nothing they have shown thus far prove that NET def is a base... I've ask a lot of people and many people have not even gotten their ne levels tested at all... How do we know that NET def isn't as prevalent as MCAD, mito, etc... So maybe NET def isn't a base it just gets dysfunctional in some patients.. Since odd are important, would and you said 1 in 20 is rare then 2 in 40 who have that NET gene abnormality should also be considered a rare finding and not a base. Like you said in Lupus they all have a specific clinical finding of a common autoantibody issue.. I don't think pots research has uncovered that yet... I also believe MCAD, mito, ect are caused by pots and not separate cofactors, but that's just a gut feeling, eds I feel might contribute to causing pots just like cancer or diabetes or Parkinson's can be primary and pots secondary.. And please don't get me wrong I think it's great they are testing these twin and I hope answers come out of it. Would be great to find twins who are older and one has had pots for 10+ years and on doesn't then to map their genes and review all clinic and environmental factor ect... Rama has said he know of this type of research going on now, so I pray they discover more pieces.. It's obvious there are many ways to damage the ans system or trigger flares in dormant systems and I admire that the researchers are trying to trigger pots to see what happens. I just think they are only at the front gate and need to step inside and take a closer look because objects may appear closer than they really are ;-)

[ramakentesh]

jangle - all quite plausible - but MIBG reuptake was only found abnormal in a subset of POTS patients (once again!).

Cerebral autoregulation is whacked in POTS. Ignore the previous study.