Pathologe. 2002 Nov;23(6):465-71. Epub 2002 Oct 08.

[Differentiation of granulomatous lesions in the bone marrow]

[Article in German]

Kvasnicka HM, Thiele J.

Zentrum fur Pathologie, der Universitat zu Koln, Joseph-Stelzmann-Strasse 9, 50924 Koln, Germany. [email protected]

Granulomas are an infrequent finding in bone marrow biopsies and may be associated with a broad spectrum of infectious and non-infectious disorders. In this context sarcoidosis generally reveals the highest incidence of such bone marrow lesions. Other granulomas may be encountered in drug-induced secondary changes (toxic myelopathy) and in particular also in HIV myelopathy. In these cases the granulomas are small, ill-defined and difficult to recognize. Special staining methods are required to detect microorganisms. Fibrin ring granulomas (doughnut granulomas) are typical for Q-fever, but may also be seen in reactive conditions, after drug therapy and in the course of other infectious disorders, such as Lyme disease. Therefore a broad serological testing should be performed. In conclusion, in most cases the morphological findings in the bone marrow are not specific so that a synoptical approach regarding histological, clinical and serological data is warranted to reach the correct diagnosis.

PMID: 12436300 [PubMed]

Since only the abstract is in English, but the article is not, I've found another similar article by the same authors, but it lacks an abstract. I'm posting the reference citation anyway though for the sake of anyone who's curious enough to want to follow up on this idea.

Kvasnicka HM, Thiele J, Ahmadi T.

Bone marrow manifestation of Lyme disease (Lyme Borreliosis).

Br J Haematol. 2003 Mar;120(5):723. No abstract available.

PMID: 12614200 [PubMed - indexed for MEDLINE]

Scott,
I know you wish I wouldn't post abstracts, but let me explain why I do. I don't feel competent to "translate" them into laymen's terms without the risk of garbling them because I know I don't have the proper academic background for doing so. I would rather that the authors' words speak for themselves.

I do try always to be selective and to choose articles which pertain, to the best of my ability to discern their relevance. I hope you won't be too annoyed that I'm interjecting these references here, because in my mind at least, they do relate to this topic concerning the pathogenesis of LD, even if not exactly to the "immunology" of LD, which seems to be your main focus here.

I've been suspecting for a long time that Bb might be hanging out in the bone marrow, as one of its favorite sequestered niches, and that this was part of the explanation of its success as a chronic, persistent infection. That's why I was so glad to find these two references.

I was also intrigued by finding the term "granuloma" within the bone marrow biopsies. That's another reason I thought that these articles are pertinent to this topic.

Suppose someone had their INF-gamma (or all their TH1 cytokines) measured and it was low and they had no signs of local inflammation (only systemic--i.e. fatigue, brain blood flow, depression) ? In your opinion, how would Benicar be benificial ?

Also, I have low IL-2. In your opinion would this suggest I also have low TNF-alpha and INF-gamma, esp since my %b Cell are high ?

I know I raised some of these points before, but not so specifically as questions.

I'm reasonably confident that if you showed enough sincere interest to do this, then I'll bet he'd be happy to guide your LLMD personally if you desired any extra help figuring out if you needed any other kind of individualized immunological testing done, as well as which labs might be the best to use.

Our past experiences in consulting immunologists was that they each had their own preferred methods of testing and of course there own way of interpreting the data. So, unless the immunologist whom you chose to consult was willing to become familiar with Trevor Marshall's ideas first, then it might be an rather expensive detour to make. You might or might not learn what you needed to know.

If your LLMD is interested at all in learning about Trevor Marshall's therapy protocol, then s/he could most likely help you figure out how to proceed in case you desired more than just the basic assortment of testing done prior to deciding whether or not to use Benicar. Maybe your LLMD would consult with Dr. Marshall in your behalf. That would probably me the most efficient and least confusing way to proceed.

http://www.immuno-sci-lab.com/2003_cat_immunology_and_serology.htm

I'm sure there's plenty of other good material about immunology in laymen's terms on the internet, too, but I'm familiar with this particular source, so that's why I chose it. I like their simplified diagrams. (Click on them to enlarge them.) You can print them out, too. It's like having "Cliff notes" for immunology, presented in a simplified format for dummies like me.

I must confess that I took the day off today from reading and studying because I was glued to the TV all day long, watching the Congressional Hearings on the abuse of Iraqi prisoners. I decided that being an informed citizen was more important today than learning immunology, because this was history in the making. I'll immerse myself again tomorrow in the pile of papers which I've printed out because I'm determined to master these concepts.

Several folks have asked me privately what my honest thoughts are about Benicar and Trevor Marshall's protocol. I'll have to confess that I don't feel I comprehend it well enough yet myself to be ready to jump into it quite yet. I will say this much in all honesty, though, that I am excited enough about it to be spending every waking minute and hour reading and trying to learn more about it.

I'm looking up the abstracts for quite a few of the reference citations listed at the end of Marshall's papers. That's a tedious and time-consuming process, but for me, it's necessary to take the time to work through things as thoroughly and carefully as that.

I'm already quite familiar with the concepts pertaining to pleomorphism and with Lida Mattman's textbook on CWD stealth pathogens and with Alan Cantwell's work on sarcoidosis. I also grasp the important difference between the families of antibiotics, such as the advantage of the protein synthesis inhibitors (tetracycline, macrolides, etc.) over the cell wall inhibitors (penicillin family and cephalosporins). So, I concur wholeheartedly with that aspect of the Marshall protocol.

I guess what worries me the most about it is that Benicar is still so new. Benicar wasn't approved by the FDA until just two short years ago, which isn't enough time for many of the adverse events to have become recognized or be reported yet. I've never had much confidence in either the FDA or in the pharmaceutical industry to tell us the truth about risks of adverse events from any new drugs. Furthermore, the dosage of Benicar is so high, and that's kinda' scary, I'll have to admit.

What I do like about the Marshall Protocol is that this combination of drugs is going to be so much more affordable, that is, if it proves to work effectively. If it does, then it will open the door to many more folks to be able to obtain therapy who are now going undiagnosed and untreated.

That's why I feel an obligation to learn enough about it first, so that if our daughter does decide to try it, that we are both well enough informed about it to succeed. I agree totally with what Byron said about either doing it right or not doing it at all.

Scott, I'm really curious about something. Your background in immunology is so strong and your knowledgeable approach to current research literature is so thoroughly academic that I'm wondering if maybe you might not have an advanced degree, beyond the DVM degree. Am I being too nosy to ask if perhaps you hold a PhD in vet medicine? (If you prefer not to reply for reasons of professional privacy, then ignore this question, and I'll come back later and delete it. It's just that I notice that you are from Ames, IA, and that's a big center for veterinary medicine, isn't it?)

And THEN I think of my 18 year old, beautiful daughter. A promising dancer, who's got unusual fatigue. She's got symptoms of both lyme (multiple tick bites) and sarc (severe photosensitivity). I'm terrified that she's going to have the same life I've had, and I don't want that for her. If Benicar poses a risk, I don't find it to be anywhere near the alternative risk of dying a slow, and painful death from this illness, or watching my daughter do the same. To me the risk to my health is nothing, if it can possibly help my daughter. I'm a skeptical person. But this time, for me, is one of those rare times where all the puzzle pieces are fitting together. And the risk seems really low, and the benefits seem significant already. The only real question for me is, will they last? Will the improvement continue? In the meantime, I'm happy to report my progress so others can wait and watch, and later decide if it might be something worth trying for them as well.

I don't want to bother Trevor with too many questions, so I'll bother you instead. :-)

I have a good friend with Hep C. He does absolutely everything right regarding nutrition, etc. And yet he's getting worse.

Since the theory is that Benicar helps the immune system work better by reducing the inflammatory cascade, do you think it could help with viral infections as well? Do they cause the same kind of inflammation, or is it a different mechanism?

The trigger for the continued inflammation is an ongoing Mg deficiency because (1) the pathogen is using Mg (2) WHILE we are using it TOO...to fight the pathogens, or try to...along with all of its other uses. (Mg is needed to make energy - ATP, control over 350 enzymes, etc.)

"A metalloprotease is an ENZYME that incorporates a metal into its molecular structure; it is not a pathogen."

(Thanks for the above correction and clarification via e-mail from a smart lyme patient!)

From my in a nutshell post:

"Metalloproteases, on the other hand, seem to be a common feature IN most bacterial pathogens."
http://cgat.ukm.my/protease/bacterial.html

So...an enzyme, called a metalloprotease, is INSIDE most pathogens - disease causing bacteria.

(Metalloprotease, by Taber's medical dictionary - definition, means: attracted to metals - usually in the mitochondria.)

And what controls over 350 ENZYMES? Mg.

Tumor necrosis factor-alpha and 6-keto-prostaglandin F1 alpha were increased when the plasma Mg concentration was below 0.15 mM...

PMID: 9558736

Once TNFs removed, neuroprotection is lost. We have also detected TNF receptor upregulation after in vitro ischaemia using immunocytochemistry.

www.meddent.uwa.edu.au/anri/teams/teamcvdl/cvdl.htm

"CONCLUSIONS: These data demonstrate a relationship between angiotensin II and intracellular magnesium and calcium. In hypertension, angiotensin II-stimulated calcium responses may be related to simultaneously decreased intracellular magnesium concentrations."

PMID: 8390527

Calcium and magnesium are needed to make healthy antibodies. Healthy ones. This is where the "damaged immune system" comes into play. If we can't make healthy antibodies, we can't knock off the bacteria...various ones. Furthermore, without enough Ca and Mg, this impacts the ability of our NK cells to work to battle the cancer virus.

Lyme patients, because the Mg levels are so low (Romanian abstract), make a lot of damaged antibodies. Up goes TNF alpha because ONE of its jobs is to get rid of unhealthy antibodies. Restoring the level of Ca and Mg, restored the health of our own antibodies (fab portion).

Hydrogen INactivates PFK which Bb is dependent on (DNA analysis). The Romanian combo. of abx.(acidic, neg. charge) and restoring Mg levels (alkaline, pos. charge) -> hydrogen production. LOTS.

To carry hydrogen INTO the cells - CoQ10. This drives the healthy, healing route to make ATP - energy via oxidative phosphorylation (using oxygen, not sugar for energy). Hydrogen, H2O2, and ATP (et. al)INactivate PFK. This is good.

All of the above is documented in my "In a nutshell part 1" post.

Get the Mg levels back up to normal and keep them there until the infection is gone...all gone.

How to restore that amt.? I fear impossible in this country. It would likely take IV doses sustained.

This is the ROOT of the problem. Mg levels are WAAAAAY down. Much more than I expected.

Scott, you said,

"Stop the inflammation and the dysfunctional response, and you stop the disease."

I couldn't agree more...just that I believe Magnesium - normal levels restored - will accomplish this.

Being a vet, I would assume you will be interested in this research also:

However, the following is curious, isn't it? (Note the date.)

J S Afr Vet Assoc. 1976 Mar: 47 (1): 29-33

The diagnosis and treatment of acid-base deranged dogs infected with Babesia canis.

Malherbe WD, Immelman A, Haupt WH, Walzl HJ.

A study was made of the acid-base status of Babesia canis infected dogs judged unlikely to recover after specific babesicidal drug therapy despite the use of blood transfusion and other conventional supportive measures.

Such cases were invariabley acidotic and responded well and often dramatically to supportive intravenous sodium bicarbonate administration. Elevated blood urea nitrogen, also responded gratifyingly to this procedure. The rationale is discussed in some detail.
http://www.sodbrennen-welt.de/science/1976/1976_4617.htm

Once again, I have pulled this from my "In a nutshell part 1" posting.

I am hoping you will take the time to read the entire post and will make the "connections" to see how and why all this fits together.

Since many are co-infected with babesia, this can play a part.

I had wanted to re-post it for you, but this topic has been moving so rapidly that I haven't been able to locate it. Hopefully, whoever it was who posted this explanation will recall it better than I can and can post it again for you.

Yes, it does all "connect" together, but we have to try to be sure that we put the horse before the cart and not the other way around.

Once more...the vitamins and minerals ALL work together. Throw one off = problems. Throw more off (abx. destroy friendly bacteria which make many vits) and = BIG problems.

The ROOT of the problem is a severe Mg deficiency. This spirals out of control.

P.S. Been in Key West. Strange place.

That's why it's hard to rely on just that one abstract from a conference which has not been replicated by other researchers.

Please, let's give Benicar a fair trial to see if it will correct the magnesium deficiency longer-term by first correcting the D-metabolite balance.

Just so you know, I spent about 3 years working hard to "balance my minerals". I had extensive mineral testing done, and was severely depleted in all of them. This was long before I started Antibiotics. My minerals just never improved, despite all my efforts.

As for flora, as Trevor and my friend Tony say, the good bacteria (flora) in our GI tracts has already been so overtaken that it's almost pointless trying to replenish it. There are even studies that show supplementing with good flora could cause problems because the more powerful bad flora swaps dna with the good flora, and now we've got even MORE bad bugs to deal with.

I've had numerous tests of my flora, and no matter how much I try to correct it, I always register almost no good flora. I receive minimal, short term benefit at best. So for me, antibiotics are not a huge risk. Of course, it's different for different people.

The good news about this Marshall protocol, is compared to most of the Lyme abx protocols, the antibiotic doses are cut way back, making the treatment far less toxic than most. We're taking very, very small amounts of abx, in comparison, because the angiotensin II blocker allows our immune system to recognize the bad bugs again. Here's a quote from Trevor from yesterday:

Author: Admin (---.vnnyca.adelphia.net)
Date: 05-08-04 22:21

Eurico,
The problem is that the bacteria causing the autoimmune diseases have parasitized the immune system itself. They live inside the very phogocytes which are supposed to digest invaders. That is why they can't be touched by any of the standard antibiotics. The only way they can be killed is if the immune system is given help recognizing them as parasites. Minocycline does this. It stops synthesis of proteins which the bacteria need to 'hide' from the immune system. Azithromycin inhibits slightly different protein transcription. Benicar inhibits different proteins again.

As your immune system gradually overcomes these bacteria, they release endotoxin, which triggers a severe immune reaction. So their death has to be paced out slowly, working at the maximum pace the patient can handle.

..Trevor..

I will say, that I'm actually herxing on the Benicar alone. I've had some atypical herxing (one night of itching), and other herxing that I'm very familiar with. Today, it's sinus drainage, and plugged up ears. This is what happens when I usually start a new antibiotic. I haven't taken any antibiotics in over a week. The Benicar alone appears to be allowing my immune system to kill bugs.

penny

Author: Belinda (---.dsl.rcsntx.swbell.net)
Date: 05-09-04 10:26

Freddie,

The promotion of vitamin D in foods and supplements has almost reached a frenzy-level, in my opinion. The articles saying most people are deficient in vitamin D are measuring 25-D, the precursor to the hormone 1,25-D the body uses. 25-D is an easier test, and they assumed that a low 25-D means the body is deficient in "vitamin D." Measuring 25-D gives only some indication of the combination of ingested vitamin D and body fat stores of same. We suspect that folks sick with other autoimmune diseases (a significant portion of the population) have elevated hormone 1,25-D when low serum 25-D is detected, just as is the situation with sarcoidosis patients. The disease causes dysregulation of vitamin D metabolism.

One other thing you should know is that the University which has produced researchers authoring papers advising more dietary supplementation of vitamin D is also the beneficiary of a foundation which holds the patent on the man-made vitamin D used in foods and vitamin supplements. The foundation was actually established to hold the patent for commercial production of vitamin D. The proceeds from D-patents alone were reported in this 1998 press release to have paid for more than half the $35.6-million price tag of a new building for the biochemistry department.

Dr. Michael Holick is usually the source quoted in magazine and newspaper articles promoting vitamin D because he works closely with a giant food company and popular media outlets for that reason. He does acknowledge the biological role of 1,25-D, but the articles supporting vitamin D supplementation are generally based on measures of only 25-D. If you read the media articles carefully, you see that the sources quoted DO say that it only takes 10-15 minutes of light exposure on the forearm to produce sufficient amounts of vitamin D in people. I admit it's hard to get beyond the horror stories about rickets and admonitions to consume foods and vitamins supplemented with vitamin D to ferret out that point in the articles, though. It's sad that fear is used to fuel the vitamin D industry.

Belinda


Re: *** My Vitamin D and ACE Test Results are back! **
Author: Admin (---.vnnyca.adelphia.net)
Date: 05-09-04 12:09

Freddie,
It is so easy for Doctors to assimilate that they have to keep the "Vitamin D" levels of their patients high. The truth is far more complicated. I suspect it will be several decades before the Vit D Industry is exposed for the sham it really is. They even stole the credit for key discoveries from Prof Tony Norman, the discoverer of 1,25-D (claiming it as their own), and now do their best to denigrate his work.

As somebody once said "You scientists make the world so complicated". Too many physicians tend to think the same way, I am afraid.

I wrote a simple article to the British Medical Journal about this issue. It just went right over everybody's heads. Take a look at this BMJ discussion thread.

quote:

---

Originally posted by free2reckon:
We know gamma-interferon (IFN-g) is raised in chronic borreliosis and probably sarcoidoisis and CFS/ME.

---

It seems that references do indicate that IFN-gamma is elevated in lyme, but wanted to raise the point that in 2500 patients IFN-gamma was not generally elevated, but in fact suppressed, in CFS,FM, GWS patients (I'm sure some of these have lyme, some don't):
http://www.springboard4health.com/notebook/nutrients_cobat_prvg.html

1) I am glad you are mentioning the possibility of other cytokine pathways, even if benicar blocks a major one, there could be others. Some of these could be more important in some people's illness than others.

2) I read the most recent paper by Marshall, as best I could anyway. There are two points that I did not get before, but do now (maybe this was already explained and/or obvious, but I just didn't understand it at the time):

First, a) Benicar only blocks one pathway for TNF-a and other inflammatory cytokines. Therefore, if this really is where the "renegade cascade" is occuring, and there is some evidence in sarc, we would only block that cascade, not all pathways for TNF-a or other cytokines that are not part of the pathology.

Second, Benicar is not blocking only TH1 cytokines. It also blocks IL-6 (TH2 cytokine). IL-6 is known to be elevated in cancer. I've read it also modulates the hypothalamic-pituatary-adrenal axis. I am intersted in that because I think the HPA axis is where I have lots of problems.

I am definitely leaning more and more toward trying this therapy even though I don't have obvious signs of classic inflammation, such as intense pain or fibro (instead mostly fatigue, brain fog, depression). IMO, I still think it will be an empirical hit or miss, but we have a clear workable model of illness and what seems to be a relatively safe drug to test it with.

I just wanted to say that I didn't have any overt pain symptoms either. They came out of nowhere, when I suddenly developed an overnight case of reactive arthritis (for all intents and purposes as I haven't actually been diagnosed with arthritis, but the joint stiffness, etc., exactly fits the symptoms).

Prior to that, I also tested positive on the FMS trigger points, even though I didn't have the kind of pain FM patients report.

However, I did come to realize that I have a high tolerance for pain. My neck and shoulder and upper back muscles have been so constricted for so long, that I've actually built up scar tissue in the area. I had an orthopedic chiropractor work on breaking those knots down and that WAS painful, and yet he said most of his patients couldn't handle the intensive therapy I got. I realize that I live with pain that I've just shut out of my mind. The only pain I really can't seem to tolerate is Migraine pain, as it makes me physically sick. But otherwise, I think my body has some ability to adjust to discomfort somehow.

I don't know, but it could be the case with you as well. That you have inflammation you're not aware of.

It's kind of funny. Before I started the Benicar, I was on low dose minocin, and I had started noticing that I was oozing very tiny amounts of pus (sorry) from the holes where my ears are pierced, even though I haven't worn earrings in months.

Also, when a periodontist looked in my mouth over a year ago, he found pus around my wisdom teeth. Odd that I wouldn't feel something, don't you think?

Anyway, not sure if this makes sense. I'm just trying to say that we may not realize we're experiencing something, even though it's happening. For me to get an overnight case of all over body pain was a serious eye opener.

It's such a relief that the Benicar has reduced that pain very significantly. The reduction of all this pain and body tension has reduced my mental tension tremendously. I haven't felt this relaxed in...I really can't say how long.