The U.S. Food and Drug Administration (FDA) is advising caution before prescribing the antibiotic clarithromycin (Biaxin) to patients with heart disease because of a potential increased risk of heart problems or death that can occur years later. Our recommendation is based on our review of the results of a 10-year follow-up study1 of patients with coronary heart disease from a large clinical trial2 that first observed this safety issue.
As a result, we have added a new warning about this increased risk of death in patients with heart disease, and advised prescribers to consider using other antibiotics in such patients. We have also added the study results to the clarithromycin drug labels. As part of FDA’s usual ongoing safety monitoring of drugs, we are continuing to monitor safety reports in patients taking clarithromycin.
Health care professionals should be aware of these significant risks and weigh the benefits and risks of clarithromycin before prescribing it to any patient, particularly in patients with heart disease and even for short periods, and consider using other available antibiotics. Advise patients with heart disease of the signs and symptoms of cardiovascular problems, regardless of the medical condition for which you are treating them with clarithromycin.
Patients should tell your health care professionals if you have heart disease, especially when you are being prescribed an antibiotic to treat an infection. Talk to them about the benefits and risks of clarithromycin and any alternative treatments. Do not stop taking your heart disease medicine or antibiotic without first talking to your health care professionals. Doing so could be harmful without your health care professionals’ direct supervision. Seek medical attention immediately if you experience symptoms of a heart attack or stroke, such as chest pain, shortness of breath or trouble breathing, pain or weakness in one part or side of your body, or slurred speech.
Like other antibiotics, clarithromycin is used to treat many types of infections affecting the skin, ears, sinuses, lungs, and other parts of the body, including Mycobacterium avium complex (MAC) infection, a type of lung infection that often affects people with human immunodeficiency virus (HIV). Clarithromycin is not approved to treat heart disease. The drug has been used for more than 25 years, and is sold under the brand name Biaxin and as generics by many different drug companies. It works by stopping the growth of bacteria. Without treatment, some infections can spread and lead to serious health problems.
The large clinical trial, called the CLARICOR trial2, observed an unexpected increase in deaths among patients with coronary heart disease who received a two-week course of clarithromycin that became apparent after patients had been followed for one year or longer. There is no clear explanation for how clarithromycin would lead to more deaths than placebo.Some observational studies also found an increase in deaths or other serious heart-related problems, while others did not. All the studies had limitations in how they were designed. Of the six observational studies published to date in patients with or without coronary artery disease, two found evidence of long-term risks from clarithromycin3,4, and four did not5,6,7,8. Overall, results from the prospective, placebo-controlled CLARICOR trial provide the strongest evidence of the increase in risk compared to the observational study results. Based on these studies, we were unable to determine why the risk of death is greater for patients with heart disease.
Furthermore, there are no prospective, randomized, and controlled trials with prespecified long-term safety outcome measures following clarithromycin treatment in patients who do not have heart disease. Because we currently do not have study information in these patients, and observational studies have shown different results, we cannot determine whether results of the CLARICOR trial can be applied to patients who do not have heart disease.
We previously communicated about this safety issue in December 2005, before the 10-year follow-up results were available for CLARICOR.
We urge health care professionals and patients to report side effects involving clarithromycin and other drugs to the FDA MedWatch program, using the information in the “Contact FDA” box at the bottom of the page.
Biaxin is a common drug used for Lyme/MSIDS. Please notice an admission is even made that the studies had design limitations as well as the fact that two studies found evidence while four did not.
As always, patients and their doctors must weigh the risks vs benefits with any treatment plan. While there are other drugs besides Biaxin, it works really well for some. Make sure to have a conversation with your doctor about this.
It is somewhat amazing to me that this study on sexual transmission of Lyme: https://f1000research.com/articles/3-309/v3 was declined by two referees but approved by two referees,yet we hear not a word of this study. It is my firm belief people are being infected sexually with TBI’s (Tick borne illness) as this is being written.
Points out there is targeted treatment for cancer. Just like cancer, Lyme is not one disease and it demands the same targeted treatment.
Early vs Late – prevention is everything.
There is genomic precision medicine to detect cancer. The same sort of precision medicine for Lyme needs to happen. Why do some do well with doxycycline while others do not? Studying genes would reveal this.
Therapeutic resistance: Lyme Persisters are a big deal. The biology for cancer and Lyme are very similar. We should learn from cancer.
Break down the silence on Lyme Disease.
EMT: cells mutate in cancer and change shape. This happens in Lyme Disease as well.
Metastatic disease – why a tumor cell goes to the brain and not the lung is built into the microenvironment. Same for Lyme. These are not random accidents.
Cancer and LD is very smart. He suggests figuring out when they change shape, what proteins change, and then target it at that point.
With cancer, they can now detect a single tumor cell in the blood. Now can also detect cell-free DNA in the blood that picks up all sorts of mutations. The same needs to happen with Lyme Disease.
If the science doesn’t impact the patient. WHO CARES
Dr. Spector never had the classic symptoms of LD and was not diagnosed due to a missed a band on current CDC two-tiered testing. His case progressed to needing a heart transplant.
Cindy Kennedy, FNP, is joined by Dr. Kenneth Liegner, who shares his thoughts about diagnosis and treatment of Lyme Disease. Dr. Liegner is a Board Certified Internist with additional training in Pathology and Critical Care Medicine, practicing in Pawling, N.Y. He has been actively involved in diagnosis and treatment of Lyme disease and related disorders since 1988.
He has published articles on Lyme disease in peer-reviewed scientific journals and has presented poster abstracts and talks at national and international conferences on Lyme disease and other tick-borne diseases. He has cared for many persons seriously ill with chronic and neurologic Lyme disease.His work has focused on the serious morbidity and (occasional) mortality that can eventuate from this aspect of the illness. He has emphasized the urgent need for widespread clinical availability of improved methods of diagnostic testing and for development of improved methods of treatment for Lyme disease in all its stages. He holds the first United States patent issued proposing application of acaricide to deer for area-wide control of deer-tick populations as a means of reducing the incidence of Lyme disease. He authored In the Crucible of Chronic Lyme Disease – Collected Writings & Associated Materials, a documentational history of the struggle to characterize the nature of Lyme disease in the late 20th and early 21st centuries, published November 2015.
Transcript of Episode 20: Tips from a Lyme Literate Physician
Click on link for the audio interview or read the transcript below.
Cindy Kennedy: Hi everybody. This is your host, Cindy Kennedy. You’re listening to another episode of “Living With Lyme.” And I am so excited to have Dr. Ken Liegner with me. And he is a well-versed, Lyme literate physician. He is well known in the Lyme treatment community, and he is what we call out here the Lyme literate doc. And you’ll see that a lot of other doctors that are as not well-versed, we don’t really call them the LL MD’s. Dr. Liegner is board certified as a medical internist, and he practices caring for people with acute and chronic Lyme Disease, as well as co-infections. He’s in Pawling, New York. He has authored countless research works, and he has also authored the book, “In the Crucible of Chronic Lyme Disease.” And I’m very excited to welcome you. Hi, Dr. Liegner.
Dr. Ken Liegner: Thank you so much Cindy.
Cindy Kennedy: I’m so happy to have you as a guest here. You are one of the top researchers, top authors, top treaters, of Lyme Disease. And I know there’s a little bit of a story back there, and I’ve read it, but tell me, how did you get started treating Lyme Disease?
Dr. Ken Liegner: Pure chance.
Cindy Kennedy: Oh, the perfect storm.
Dr. Ken Liegner: I just stumbled into it.
Cindy Kennedy: You did. You did. Did you get roots … Did you form your roots in the New York area, or were you always there?
Dr. Ken Liegner: Well, I went to medical school at New York Medical Collage in Valhalla, New York, in Westchester County. And then I did some training there, and then I went elsewhere. And then I was in Washington DC for a year, doing surgical critical care at Washington Hospital Centers MedStar Unit. And it was great training, and it’s the kind of training I wanted to have, very broad training, but I really decided that’s not what I wanted to do for a career. It’s quite grueling type of work, and so I decided to come back to Westchester County to start a private medical practice. That was around 1985 or so, and we decided to purchase a home. And I chose a home that was, I thought, suitable to turning the lower floor into a medical office. It was a raised ranch, and took out a business loan with Chemical Bank for 80 grand, which was very scary thing to do.
Cindy Kennedy: That’s great now, if you could get something for 80 grand in that area.
Dr. Ken Liegner: No, that was just for the renovations.
Cindy Kennedy: Oh, oh I see.
Dr. Ken Liegner: That was the renovations to turn basically a semi-finished basement into a medical office. Then I hired a contractor to build it out, and hung up my shingle, and waited, waited for the word to discover me.
Cindy Kennedy: And then, what? People were just coming in with crazy symptoms, and what happened?
Dr. Ken Liegner: Well, initially I just kind of did general medicine, and did a little bit of critical care at my hospital. Back in those days, I was the only critical care physician, because it was a new field, critical care. So I did some of that and did some general medicine and saw a wide variety of patients, and my house, it was a house. It was a home office in a little sort of a cul-de-sac area, so some of the people would be neighbors up the street would come in, and did general medicine. Then I started seeing patients with this new entity, Lyme Disease, which trust me, I knew virtually nothing about it. I just knew the name. That’s all I knew. And they were interesting cases, and challenging, puzzling, new disease. And I started seeing more patients, and then I realized they were strange. They were odd. They didn’t seem to behave the way they were supposed to behave. And so that was intriguing. So that was around ’85. I started seeing patients, just because at that time, there really was a burgeoning epidemic in Westchester, so that’s what I meant. I just kind of plunked myself down into this burgeoning epidemic, unbeknownst to me what I was getting myself in for. And then around 1988, there was a local library, which was on a sort of an expansion plan. It was a little tiny library in Armonk, and they were doing a building expansion thing, and they asked me if I wanted to do a talk. And in fact, I arranged a medical series for them, and I decided to talk on, guess what, Lyme Disease, because I was seeing these patients. I didn’t know all that much about it at the time, and I took advantage of the medical library at Northern Westchester Hospital Center in Mount Kisco, and over a couple of three months, I reviewed a lot of the then available world literature, which in 1988, wasn’t that much, so in three months, you could really review a lot of it. And I gave a talk in the basement of this library, and there was a lot of interest in Lyme, because a lot of people were getting sick. People didn’t know a lot about it, so I gave this talk, turns out that the basement of this library was chock full. It was 300 people crammed into this basement of this library, so I gave my talk. All of a sudden, I’m an instant expert.
Cindy Kennedy: Wow, there you go.
Dr. Ken Liegner: Okay, but I knew I wasn’t an expert. It’s just because I’d reviewed the literature. I knew more than anybody else around at the time, and so that’s when my practice started kind of exploding with patients with tick borne illness. And it kind of grew from there.
Cindy Kennedy: What kind of testing was available back then?
Dr. Ken Liegner: Well, this is back in the day when there was not very much testing available. In fact, I was just going over some records with one of my staff from back then. We didn’t even have Western blots.
Cindy Kennedy: So what were we looking at?
Dr. Ken Liegner: All we had back then was ELISA, enzyme-linked immunosorbent assay. I mean, Western blot at that time was really a big deal research thing. You couldn’t really get them that easily. Of course, then they became to be more widely used, and it was fairly standard to get both an ELISA and a Western blot. But back in the day, all you had was the ELISA and the clinical.
Cindy Kennedy: Right, right, well that’s-
Dr. Ken Liegner: So it was a … Sorry.
Cindy Kennedy: That’s okay. Sorry. That’s so important, because we all know that Lyme Disease, and you wanna shake the medical community, because you got people here that are not testing positive, and truly they need to be treated on a clinical basis, and then we end up with people being misdiagnosed and these healthcare providers just not really getting it. And so now we’ve got a whole host of people that are still sick, and time is going on, and going on, and going on, and now we’re into what we call chronic Lyme Disease. So give us an idea of what that is. How do you classify it, and is there a diagnosis?
Dr. Ken Liegner: What do you … Is there a diagnosis? Cindy Kennedy: Well, that’s not what I meant. Is there criteria to be sent-
Dr. Ken Liegner: Oh, well, yeah, I mean, it’s very interesting. To say that there’s not such thing as Lyme on a chronic basis, whether it’s treated or not treated is absurd to even question that. It’s as though you would say, is there such a thing as late-stage syphilis. Nobody questions that. But for a wide variety of reasons, a lot of them political and socio-economic in nature, the idea that there might be such a thing as Lyme on a chronic basis, even following treatment, there has been, I would say, a manufactured controversy about this, something that is so obvious, it’s ridiculous. I mean, the idea that there’s even any controversy about that itself should … How shall I say it … should invite scrutiny about just why that is.
Cindy Kennedy: Right, right, and that could be a whole other episode, but I can only imagine, if we were back in the Western days, and we had one group of people that were firm believers and one group of people on the other end of the saloon that wasn’t believers, that we could have a big shootout over this. This could raise a lot of tempers, and I’ve seen it happen. I, as my listeners know, I’m a nurse practitioner, and I do have physicians as patients, and I will say that if … I’ve brought up the idea about Lyme Disease, and I get some ridiculous statements, the fact that oh a tick has to be on for more than 36 hours, and it takes that long for them to regurgitate. And I just shake my head. I’m like, you can’t do that. There’s such a small percentage of people that even get a bullseye, and so we’re doing a very bad job of early diagnoses of this kind of condition. One of my biggest questions here is, is there a timeframe where you feel that if people have had symptoms more than six months, they’re more chronic, or is it geez let’s treat them and see if their body responds, their immune system picks up, and now they will not be chronic? How do you feel about that?
Dr. Ken Liegner: Well, in process, there’s an attempt to define exactly what chronic Lyme Disease is, in a formal definition. A lot of people use a cutoff of six months of symptoms or six months untreated as a cutoff, not just for Lyme but for other conditions that get the name chronic. Some would arbitrarily use that as a cutoff, and when I use the term chronic Lyme, what I mean is that the illness is due literally to the Lyme Disease organism or closely related organisms that fall within that species or related species and that the illness is actually due to that in particular. Some people try to lump that with other tick borne co-infections, and those are bonafide, and real, and they certainly can make the picture much more complicated, but what I mean when I talk about chronic Lyme Disease, illness that is due to ongoing infection, not post-treatment Lyme Disease syndrome that implies that it’s a post-infectious, non-infectious entity. And as you know, people have proposed that as an alternative to chronic Lyme, which again, I think, for political reasons, has gotten a lot of opprobrium attached to using that term, and I think that’s completely political smear tactics.
Cindy Kennedy: Okay, what is an opprobrium? I don’t have a dictionary with me.
Dr. Ken Liegner: Opprobrium, hateful ridicule that is directed at the idea of chronic Lyme, because it’s a ridiculous idea. Of course, no such thing exists, right? That’s tongue in cheek.
Cindy Kennedy: Well, here’s the problem. You know what? I don’t care what you call it. Let the people on the other end of the saloon give it a name, but why do people suffer? And what can we do about it?
Dr. Ken Liegner: Well, basically, scientific research and education is what is needed.
Cindy Kennedy: Right, but what do you do for the person that’s sick, and has been sick, and has been treated, and for a prolonged period of time?
Dr. Ken Liegner: Well, you have to do one’s best to try to figure out what in the world is wrong with them, and maybe it’s Lyme. Maybe it’s something else. Maybe it’s co-infections. And there does exist a lot of possibility for errors in diagnosis in both directions, meaning the people who have other conditions could be misdiagnosed with Lyme, on the one hand, and then people with Lyme Disease, because of it’s very wide range of manifestations, can be misdiagnosed with some other non-infectious conditions and get all kinds of treatments. Some of that treatment can be very toxic and dangerous for a condition that actually often would respond to fairly simple, relatively inexpensive antimicrobial therapy.
Cindy Kennedy: Okay, so I know that I’ve learned the problem rests with the individual’s immune system. What’s going on with the immune system?
Dr. Ken Liegner: Well, the immune system is crucial, critical, and it’s often been said that if one has any kind of an infection, even if it’s just a strep infection, although antibiotics are helpful, ultimately it’s the role of the immune system to eradicate the infection, eradicate it or contain it if it can, and if you don’t have a functioning immune system, ie HIV, AIDS, for example, or other immune deficiency states, antibiotics can become relatively ineffective or completely ineffective. So yes, the immune system is extremely important.
Cindy Kennedy: I understand that a prolonged infection, and we know that the spirochete of Lyme Disease can take on different shapes. It can hide. It can burrow into tissue. It can burrow into organs. And it does do a number on your immune system. Am I correct?
Dr. Ken Liegner: I think you are correct. A lot of people have had that concern, and there’s actually a good deal of scientific study that demonstrates that. Most notably, that sticks out in my mind is the work of Nicole Baumgarth. I think she’s from out in the West coast, maybe Irvine, University of California. I think she’s from Irvine, demonstrating in a mouse model, that the Lyme organism completely disrupts the germinal centers of the lymph nodes and other organs of the reticuloendothelial system, so in order for things to progress and be recognized by the immune system, you need an intact immune system. And there’s an architecture to the lymph nodes that includes something called germinal centers. If you take a lymph node and cut it in half and look at it under the microscope, using certain stains, you’ll see that there are, within the lymph node, there are sort of little spherical areas that have an architect to them, and those are necessary for to develop the IGM response, and then over time, there’s what’s called class switching, from IGM to IGG. And a lot of different immune cells are involved in that. And in a mouse model, of course, a mouse is not a man, but in a mouse model, Nicole has demonstrated that architecture gets completely disrupted. And often, you will see persistence of the IGM response and a failure to class switch to IGG, and of course, a lot of us dealing with the patients with that disease that doesn’t exist, chronic Lyme Disease, you see that very commonly.
Cindy Kennedy: I’d like to explain to the listeners the difference between IGM and IGG. And the IGM, I’ll take something more simple like Chicken Pox. Someone gets infected with Chicken Pox, they’re going to produce the initial antibodies, which are called IGM, and we always say modern, so we remember the M. and then after a period of time, after you’ve had the illness and you create more long-term antibodies, you basically lose that IGM, and you have what we hope is a persistent IGG, and that shows that you have had exposure to it. Even in somebody’s case that they haven’t gotten very sick with, say, Chicken Pox, that’s where we know that the exposure has occurred, and you’ve built antibodies against it, just in case people don’t know what the IGM and IGG is.
Dr. Ken Liegner: That’s correct.
Cindy Kennedy: I don’t know if I really wanna hear the answer to this, but do you use the CD57 test?
Dr. Ken Liegner: Personally I don’t.
Cindy Kennedy: You don’t.
Dr. Ken Liegner: I know some of the colleagues do use that.
Cindy Kennedy: Yeah, that seemed to be the biggest way I was diagnosed, and some IGeneX labs that kind of came back consistently not positive and not negative, kind of indeterminate, but ever since there’s been a lot of exposure to this podcast, there’s been other podcasts done for Resilience Radio, where they’ve asked me to be a guest. I’ve had some exposure via news, and also our local paper did a wonderful article. I’ve gotten a lot of emails and notification through Facebook. And people feel like my journey is very similar to theirs, so let’s just walk through me as a case study. So I come to you. I have had a variety of symptoms for a persistent period of time. I’ve been sent to you, because I’ve had to take care of myself practically. I’ve seen Rheumatologists. I’ve seen PCP’s. I had a sleep study, because I was having such trouble sleeping. The fatigue level was horrible. At this point, my hands are still swollen, and X-rays show some fluid in the capsules in my knuckles, in my wrists, but everybody’s I don’t know. I don’t know. I don’t know. Nobody knows what the heck’s wrong with me, so I come and I see you. And we do some tests and clinically, that’s the angle we have to take, so we get treated, antibiotics, oral, triple antibiotics. Neurologic symptoms are occurring, just personality issues, forgetfulness, and at that point, I had a PICC line, so put a PICC line in, antibiotics IV for a period of time, then a really bad allergic reaction, and we just kind of said, that’s enough of that, did in the process, because of clinical symptoms, get treated for Babesia. And so after that, when I was done with the antibiotics, and I really needed to try an alternative route, doing some homeopathy, doing some supplements, etc, periods of time, up and down, just still don’t feel well. And so this is what a lot of people have, and they don’t know where to go. What would your suggestion be?
Dr. Ken Liegner: Well, as a physician, want to just underscore the importance of very careful history, taking a very careful history, in terms of what kinds of symptoms the person has had going back to the onset of their illness. When was the last time they felt rather well, and what changed? It’s very important to ascertain some basic things, like have they had any definite known tick attachments or eruptions that might have been consistent with erythema migrans, the rash of Lyme, and/or have they had significant opportunities for exposure to ticks and disease that they carry in areas that are known to be endemic for Lyme and tick-borne diseases. And of course, if you query almost any human and speak to them in enough depth, it will turn out that they’ve had some exposure, because I mean, ticks are fairly ubiquitous people, live in different places. They vacation, and so I mean it’s hard to think of a person who might not have had any risk.
Cindy Kennedy: Well, the other thing that, most people have dogs, and the dogs are fairly well protected with all of their Seresto collars, or sprays, or their Frontline, or Advantix stuff, and they bring them into the home.
Dr. Ken Liegner: Exactly, indoor/outdoor pets can be the so-called Trojan horse. No matter how careful you are, and even though you may treat these animals, a lot of the treatments that we have, what they do is they kill the ticks on the animal when the tick feeds but does not necessarily kill the tick when it’s on the coat of the animal. So in other words, theoretically, an indoor/outdoor pet could bring ticks into the home that can go off the animal, onto the carpet, or onto the bedding, and I think animals are wonderful, but especially if they’re indoor/outdoor, they can pose some risks. And also, ticks, if you didn’t know it, they will actively seek out their hosts, and they can detect carbon dioxide and will follow carbon dioxide gradients to find a host. So yeah, and it’s also important to emphasize, many people who really and truly have Lyme, and bullet proof cases of Lyme never give a history of known tick attachment or of a recognized rash. And of course, that’s often people show up years later quite ill with fully diagnostic tests if they’re lucky, and they went for years, because nobody really though about Lyme, because they didn’t come in saying, I had a tick bite and a rash.
Cindy Kennedy: Right. For people who don’t know, when we talk about carbon dioxide, that’s actually what is in our breath as we breathe out.
Dr. Ken Liegner: Correct.
Cindy Kennedy: Yeah, so they’re just looking for breathing people, so everybody has to breathe.
Dr. Ken Liegner: Or critters, it doesn’t have to be people.
Cindy Kennedy: True. True.
Dr. Ken Liegner: By the way, there’s a great book that I’d like to plug called, “Dead End Host.” Have you ever heard of that book?
Cindy Kennedy: No. “Dead End Host.”
Dr. Ken Liegner: “Dead End Host,” you can get it on Amazon. It was written by Dan Ardrey. Do you know who Dan Ardrey is?
Cindy Kennedy: No, give me the info.
Dr. Ken Liegner: Well, do you remember a book from back in the day, in the ’60’s or ’70’s called … What’s it called … “African Genesis.”
Cindy Kennedy: Now, I don’t wanna date you-
Dr. Ken Liegner: It’s okay.
Cindy Kennedy: Yeah, well, I probably was just learning my alphabet back in the ’60’s.
Dr. Ken Liegner: Well, anyway, Robert Ardrey was the author of that book called “African Genesis,” which made quite a hit in the ’60’s. And Dan is the son of Robert Ardrey, which I didn’t realize that for many years. I didn’t realize that Dan was Robert Ardrey’s son. But anyway, Dan wrote, I thought, and excellent book about his own experience with Lyme Disease. He contracted it, I think, when he visited the Lower Hudson Valley. I think he was at Bard College. It’s a long story. I thought very, very interesting, very well researched, very well referenced. And he tried to get it published, and he had showed me a review copy. This has gotta be 20 years ago. He showed me a review copy. I thought it was excellent. He made the mistake of submitting it to the Harvard University Press, and one of the reviewers was, who I don’t know for sure who it was. I have my suspicions who the reviewer was, but it was just the most vicious review, and I think reflecting the politics of the day. But Dan persevered, and as electronic publishing became possible, he actually had the book published, or self-published it. And I have nothing to gain by this, but I would highly recommend Dan Ardrey’s book, “Dead End Host.” It’s an excellent book. Anyway, I don’t know how I got onto that.
Cindy Kennedy: No, that’s okay. We all do that. The biggest concern is, is there hope? A lot of people are depressed. They don’t feel well. They’re not finding the help they need, or they have been treated and for a significant period of time. Is there hope that these chronic Lyme sufferers are going to get better, and what would you say they need to do?
Dr. Ken Liegner: Well, first of all, I believe there’s hope. I believe that we could and can have better methods of both diagnosis and treatment, not only for Lyme Disease but the other so-called tick-borne co-infections, and that is beginning to happen. So it’s a time that things are looking more encouraging than they have for a long time. We know there are at least three or four academic groups who are actively working to determine if we can develop improved methods of treatment for Lyme. There’s Kim Lewis’s group at Northeastern University, Ying Zhang’s group at Johns Hopkins. There’s a gentleman named Jay Rajadas, who’s at Stanford and also Eva Sapi. They are all looking to new approaches to try to develop improved methods of treatment, and also at the same time, we are on the cusp of improved methods of diagnosis as well.
Cindy Kennedy: Oh, I’m so excited.
Dr. Ken Liegner: I mean, that’s been a big part of the problem obviously. A big part of the problem is the misuse of the two-tier system of testing that was developed by the CDC supposedly intended strictly for epidemiologic purposes but widely misused by the insurers to deny people both diagnosis and reimbursement for care.
Cindy Kennedy: Oh, it’s awful. It’s awful. Back before, in Massachusetts, but back before they passed a bill that said that insurance companies mandated by the state of Massachusets could no longer deny antibiotic coverage. My insurance company was rah rah, cis boom bah, up until day 28, and then day 29, there was no antibiotics at my door. And we got a letter saying at that point everything else was experimental. And I’m like, are you kidding me? So then now the venture goes out, and I gotta find out how can I pay for this, and as you know, people can lose … They lose their income, because they can’t work. They lose savings. They lose family, marriages, that whole thing, and it’s unfortunate, and I can only hope, that with the amount of infections, and cases, and people really opening their eyes to this, that we can get some big changes, because it’s truly unfortunate. And I know that there are people that are really suffering out there, and their quality of their life is very poor.
Dr. Ken Liegner: Well, what has happened is that the situation has gotten so bad, because of severely misguided policies, that wide swaths of the population are affected, including guess what? Legislators, their children, their wives, their staffers, themselves, and you get enough of that, and all of a sudden, things begin to change, so it becomes feasible for there to be legislation. And that affects policy. The amount of resources that have been allocated to Lyme and tick-born disease over the past 30 years is pitiful.
Cindy Kennedy: It is.
Dr. Ken Liegner: And a lot of it has gone to certain individuals who continue to promote the notion that there’s no such thing as chronic Lyme Disease. There’s no such thing as so-called seronegative Lyme Disease, meaning Lyme Disease existing when the standard tests are negative, and that’s a big, big issue. And so called direct detection methods, some of which have been developed, some of which have been promising, and then moth balled, which would enable the doctors and the patients to know with confidence who really has Lyme Disease and who doesn’t, and also not only do they have it, but what is the status of the infection? A lot of those methods have been suppressed for political and socio-economic reasons.
Cindy Kennedy: What do you think is the best Lyme test, or as I have read and learned, that really you kind of gotta use a variety of testing methods.
Dr. Ken Liegner: Yeah, well, clinical is extremely important, and clinical suspicion is important, nonetheless, you still want to, if you can, use the methods that are available to try to figure out what is going on. There’s no “best” Lyme test right now.
Cindy Kennedy: There isn’t, okay.
Dr. Ken Liegner: Many of us need to use a range of methods, including the screening test, the ELIAS so-called, and the Western blot. We usually send that to at least two different good laboratories, because we have found you can not rely on a single laboratory, even a good laboratory. You also use whatever direct detection methods are available right now. In New York state, we are able to use preliminary chain reaction as a method. There are other methods that have been developed and are beginning to be utilized. For example, CERES, C-E-R-E-S, CERES nanoscience has their Lyme nanotrap test, which is an antigen detection test in urine, that’s not yet available in New York state, but it is becoming available in other states. And again, there are other cutting edge research tools that are on the horizon, but they’re not quite ready for primetime.
Cindy Kennedy: Right, so we just gotta hold on, hold on a little while longer. And so before we wrap up here, your information is wonderful, and I do know that you and your nurse practitioner are taking on new patients. And I did travel to Mount Kisco for treatment, and I can tell you it’s doable from Western Massachusets. And so I encourage people who are listening to this podcast and have suspicion, and you’re not getting the appropriate answers, or the appropriate treatment, to possibly go visit Dr. Liegner or his nurse practitioner. But I have a couple of funny questions for you, and I didn’t tell you about that. Sometimes I do, but I had forgotten, so I apologize. You said you wanted things to stump you, so here we go. Ready?
Dr. Ken Liegner: I said I was expecting some curveballs.
Cindy Kennedy: Okay, here’s one. What ticks you off?
Dr. Ken Liegner: What ticks me off? Oh, well, the injustice that persons with Lyme Disease have suffered over the past 30 years. Also ticks me off that the physicians who have treated the patients have also suffered quite a bit of injustice as well. But it looks to me like there might be some comeuppance.
Cindy Kennedy: Okay, all right, well see you didn’t flinch.
Dr. Ken Liegner: No, you’re aware of the litigation that recently was undertaken, right?
Cindy Kennedy: Tell me.
Dr. Ken Liegner: You’re not aware of it.
Cindy Kennedy: I might be, but tell me and tell my listeners.
Dr. Ken Liegner: Well, there’s a woman named Lisa Torrey. She and another patient … I’m not sure the pronunciation of his name, something like David [inaudible 00:35:35] or something like that. They, over the past 10 years or so, apparently, decided to take it upon themselves to really build a case for collusion by certain players, along with the insurance industry, to essentially defraud the American public. And they did all the groundwork, and they presented it to several groups of attorneys who have deep experience in this area. And what I was told was that before the attorneys agreed to take the case, the groundwork that Lisa and her other coworker did was presented to academic legal experts at Harvard, to ask them whether there really was a case, and the answer was in the affirmative. So that was recently filed, and I’m sure it’s available. It’s a civil action. It’s 53 page brief, and it’s available for people to review on the internet. And I did go through it, all 53 pages of it, and I think they build a very compelling case.
Cindy Kennedy: I did read something about something that was going on in Texas, and that was against … Is this similar or the same?
Dr. Ken Liegner: It’s the same.
Cindy Kennedy: It is, okay, so it is that. I did read about that. I didn’t get the names, so gosh, there’s some good changes, and I’m really happy to see that. It’s just so difficult for both patients and certainly the caregivers, like yourselves, and many others that are just so frustrated and put on the spot, and kind of blackballed by other members. But one more good question, Lyme is something that has allowed me to get a big fat lemon in my lap, so I decided to make lemonade, and in life, I’m sure you’ve gotten a lemon somewhere. I hope it wasn’t a car, but what’s your lemonade?
Dr. Ken Liegner: Well, there’s the same situation. I mean, trust me, I didn’t go looking for Lyme Disease. Like I said, it was chance, circumstance. It turned out that it was so-called a niche that needed to be filled. And I happen to fill it. And I’ll tell you one thing. It hasn’t been boring.
Cindy Kennedy: No, I bet. It hasn’t been boring, because it’s all shapes. It’s sizes. It’s ages. It’s genders, nationalities. It’s all of that. No one’s really safe.
Dr. Ken Liegner: Well, it’s been very, very challenging, and also, intellectually and scientifically, actually extremely interesting, and quite a learning experience. And it also, it so to speak tests your mettle as a physician, because this is what being a physician is all about or should be, listening to the patient, examining the patient, using the scientific tools that are available to try to figure out what is going on. It really is a very challenging illness. And it’s a new illness.
Cindy Kennedy: You have to have your eyes. You have to use your eyes, and you have to listen. You have to listen with your ears, and the scenario that just at this point makes me crazy is that I got treated with three weeks of Doxycycline, got sent over to a Rheumatologist. I said to him, I’m 75% better, and he just shrugged his shoulders and said, “Well, I don’t know why.” And so that’s where the ball got dropped, that if I got treated longer, if he was wiser, if he believed in the theory of a negative test does not mean a non-infection, then I wouldn’t be faced with what’s going on with me today. So that being said, I welcome change. I really, really do, so I thank you so much for all this great information, and if you had one bit of advice for people who are listening, who may be suffering or know someone who’s suffering, what would you advise them to do?
Dr. Ken Liegner: As my patient Dickey Logan once said, “If you think you have Lyme Disease, you have to pursue the diagnosis.” And also, don’t give up hope. Don’t give up.
Cindy Kennedy: Yeah, I think a lot of people do give up hope, because it’s a very overwhelming and taxing for a variety of … the individuals, their families, whatever. I don’t know if anybody here’s all that panting and whatnot. My dog, my daughter’s dog, is here, and he’s getting all excited about my producer here Doug.
Dr. Ken Liegner: What kind of a dog is it?
Cindy Kennedy: I have two Labs, and this is another Lab, so we have all three colors here. We have a chocolate, a yellow, and my daughter’s dog’s a black Lab. That’s our mechanism to get ticks in the house, I guess, huh?
Dr. Ken Liegner: They’re nice animals.
Cindy Kennedy: They’re awesome. They’re awesome. And one other question I wondered, did you ever suffer from Lyme Disease yourself?
Dr. Ken Liegner: No, I didn’t.
Cindy Kennedy: Good. Let’s keep it that way. Stay in the library.
Dr. Ken Liegner: Right. Well, I don’t step on the grass where I live unless I am in knee-high boots that are pre-sprayed with Permethrin.
Cindy Kennedy: Wonderful. Wonderful. Well, I thank you again, and I look forward to seeing you again, because we do run into each other from time to time, and I hope all my listeners have really enjoyed this episode. It’s a very, very eye opening and actually heartwarming and giving us a lot of hope, so for all of my listeners, I thank you for listening to this episode. You’ve been listening to “Living With Lyme,” and your host Cindy Kennedy. And this has been Dr. Ken Liegner. And come back, listen to another episode, and do subscribe to the website to get more podcast information. And that’s at http://www.livingwithlyme.us. I’m gonna sign off here, and take good care.
Overview on the management of non-gastric MALT lymphomas.
Defrancesco I, et al. Best Pract Res Clin Haematol. 2018.
Abstract
Extranodal marginal zone B-cell lymphomas (EMZLs) of the mucosa-associated lymphoid tissue (MALT) are indolent lymphomas (slow growing) which can present at any extranodal site. The most frequent localizations (other than stomach) are ocular adnexa, salivary gland, skin, lung and thyroid.Chronic inflammation and antigenic stimulation are a potential risk for the development of MALT lymphomas. While Helicobacter Pylori (HP) is known to be associated with gastric MALT lymphoma and antibiotic therapy is effective in the setting of HP-positive, other microorganisms (such as Chlamydophila Psittaci, Campylobacter Jejiuni,Borrelia Burgdoferi) have been implicated in the pathogenesis of non-gastric MALT lymphomas. However, antibiotic therapy has not been extensively investigated for the non-gastric type, except for ocular adnexal MALT lymphoma, which could benefit from an upfront treatment with doxycycline. Surgery, radiotherapy, Rituximab alone or in combination with chemotherapy and “chemo-free” approaches, including lenalidomide, have shown efficacy in the treatment of non-gastric MALT lymphomas.
Lyme/MSIDS patients are always looking for relief. The pain we endure is indescribable. We clearly understand most of the pathogens we are dealing with are persistent, despite the CDC/IDSA/NIH denial. Our experience shows that we function well off treatment for a while and then the dreaded symptoms return. We cycle in and out of treatments which are expensive, time consuming, and often have significant blow-back. While antibiotics kill or disable bacteria, we all know they disrupt the microflora of the gut and damage mitochondria. Similarly to other treatments for other diseases, say cancer for instance, sometimes the treatment is as bad as the disease and some are affected more negatively than others.
This article is about two substances that you should learn about and discuss with your medical practitioner. These two substances are described as “therapeutic principles,” – not drugs. In many aspects they are quite similar and one is derived from the other.
It’s important to condense and overlap treatment modalities as much as possible for two reasons: time and money. Another lesson Lyme/MSIDS patients learn is this disease can take over your life and cost you everything you have since it’s a long-term treatment – perhaps life-long. I believe the substances in this article to be worth real consideration as they do so many things simultaneously, and are cheap & effective for most who use them. I apologize up front for the meandering nature of this article but after you read and digest it, you will understand why. So much is interconnected!
As always, this article is meant for educational purposes only and not meant in any way to diagnose or treat.
DMSO
Dimethyl Sulfoxide (DMSO) is a colorless, odorless, transparent substance obtained from wood; however, small amounts are naturally present in common foods such as milk, tomatoes, tea, coffee, & beer, among others.
First discovered by Russian chemist, Alexander Mikhaylovich Zaitsev in 1867, today DMSO is obtained as an industrial by-product from lignin in paper manufacturing. Because of its polarity and low acidity, it is a highly aprotic (doesn’t yield protons) solvent that can be mixed with other substances to increase their effect. It’s ability to penetrate biological membranes and transport other substances with it has also made it an excellent carrier.
Hartmut P.S. Fischer has explained in great detail in his groundbreaking book, “The DMSO Handbook: A New Paradigm in Healthcare,” the structure of DMSO and its chemical properties as well as the following brief summary of pharmacological properties on humans and animals:
These qualities play out in reducing pain, alleviating inflammation, diuresis, vascular dilation, free radical scavenging, wound healing, and muscle relaxation. All issues Lyme/MSIDS patients deal with at some point.
The father of the medical use of DMSO, Dr. Stanley Jacob, enjoyed notoriety in the 60’s but admits the reception was short-lived due to DMSO’s long list of pharmacological properties and its being labelled a “miracle medicine.” In other words it did too many things to be taken seriously. The FDA approved DMSO for preservation of stem cells, bone marrow cells and organs for transplant, as well as for therapy of interstitial cystitis and cancer radiation protection – by prescription. It’s also used under medical supervision to treat several other conditions, including shingles. DMSO is available without a prescription in gel, cream, or liquid forms. It can be purchased in health food stores, by mail order, and on the Internet.
MSM, which in the second part of this articleis derived from DMSO, is considered a methyl donor and reduces homocysteine levels suggesting a role in the methylation process and in reducing oxidative stress. Since many patients struggle with high homocysteine which leads to inflammation and neurological problems, this is another boon for Lyme/MSIDS.
Speaking of Methyl donors, I would be amiss if I didn’t mention their importance in the issues of mood & energy:http://www.raysahelian.com/methyl.html(I have no affiliation with any products)
DMSO has been used for cancer and an article by Camelot Cancer Care states the reason it protects against radiation damage and side-effects of traditional cancer treatments is due to how it stimulates parts of the immune system and scavenges hydroxyl radicals that promote tumor growth.http://www.mnwelldir.org/docs/cancer1/dmso-faq.htm Since this usage is considered “off label,” insurance companies can not be billed for it. Go to link for more info on how it’s used for cancer.
A small but significant bunny trail:
Speaking of cancer, I’ve done my own experiments against basal cell carcinomas on my face and leg. I’ve had two MOHS surgeries on my face – both of which were expensive, painful, removed skin, and took time to heal. Since they were close to my eyes, the doctors believed I would need subsequent plastic surgeries to be able to blink and produce tears. I stood my ground to attempt using ozonated olive oil in the healing process to see if I couldn’t avoid these unwanted surgeries. Below is the result and I’m happy to say I was right:
Since the two MOHS surgeries I have developed more basal cell spots. Thankfully my LLMD knows about CURADERM BEC5 treatment – an egg plant derivative with salicylic acid. Curaderm targets the cancer cells and destroys them while the salicylic acid sloughs the old dead skin away.Directions here. It will not target normal cells.
In my case the cancer was deep (60+ years of living next to water and lots of sun) which became painfully pussy at times during CURADERM treatment. Eventually it’s quite obvious that as the old, dead skin sloughs off, new virgin skin rises to the top. I won’t lie: it can be extremely painful. It’s important to take a wet wash cloth to help remove the dead skin and then reapply and cover the area with CURADERM and occlusive tape. Apply twice a day until lesions are completely gone and are replaced with normal skin. Word of warning: the tape sticks fast and can pull skin off when you remove it. This also is painful. At times I would cut bits of sterile gauze to put over these sensitive areas before covering with tape. This stopped the problem. There is a skin colored tape and a white tape. I found the white tape to be more gentle, albeit more noticeable! How much are you willing to suffer for vanity?!
All that said, my next experiment will be with ivermectin paste for basal cell carcinomas.
**UPDATE**
Both ivermectin and panacur (fenben cream) seem to work on all my basal cell cardinomas. I still utilize CURADEM because it actually searches for cancer cells. This can often create an ‘iceberg’ effect where you start out with a tiny scab that won’t heal and end up with a much larger affected area. I believe in keeping the pressure on so will use CURADERM for a couple days back to back and then ‘rest’ by then using either ivermectin or panacur for a few days back to back. The CURADERM requires a covering to keep it moist but you can expose both pastes to air and be fine. Panacur will eventually dry (it takes an hour or so) but the ivermectin I use is more of gel that doesn’t dry per say. If it’s on an area clothing will rub it off, simply put gauze and tape over it. Make sure to apply all of these modalities TWICE a day.
Cutaneous manifestations of scleroderma (an autoimmune rheumatic disease) appear to revolve following topical applications
IV DMSO may benefit amyloidosis (an abnormal protein builds up in tissues & organs)
Dermal application provides rapid, temporary, relief of pain in arthritis and connective tissue injuries
Animal studies indicate IV DMSO is as effective as mannitol & dexamethasone in reversing cerebral edema (brain swelling) and intracranial hypertension (a neurological disorder where cerebrospinal fluid pressure is high in the skull)– a human clinical trail in 11 patients supports this
DMSO is used with mixtures of idoxuridine in the UK for topical treatment of herpes zoster
Adverse reactions are related to the concentration of DMSO and are usually minor
According to Dr. Jacob, “DMSO is a potent free-radical scavenger and diuretic that reduces swelling and improves blood supply to the brain… “we observed that when the human brain was treated with intravenously administered DMSO after a head injury, the swelling could be reduced within five minutes. No other treatment comes close to acting that quickly.
Astonishingly, however, the Food and Drug Administration (FDA) has not approved any new pharmacological agent of significance for the treatment of traumatic brain injury in more than three decades. With so much attention focused on the plight of severely injured soldiers returning home from war, Dr. Jacob is leading the charge to gain FDA approval of DMSO to treat this type of injury. He believes that DMSO would be more effective than some current therapies such as removing parts of the brain to reduce swelling.
Dr. Jacob and his colleagues previously sponsored preliminary clinical trials of DMSO on traumatic brain injury patients in Europe. The results of the trial were remarkable, with an 80% survival rate (about twice the historical rate of 30-40%) and 70% of the patients experiencing a favorable outcome (far higher than the historical rate of less than 10%).1
https://www.ncbi.nlm.nih.gov/m/pubmed/19443933/ The effects of DMSO make it potentially useful in the treatment of medical disorders involving head and spinal cord injury, stroke, memory dysfunction, and ischemic heart disease.
How’s all this relate to Lyme/MSIDS? Glad you asked.
First, many with neuro-Lyme have brain swelling. Excruciating head pain is a hallmark symptom – often worsened with Babesia & other coinfections. Second, many Lyme/MSIDS patients suffer with various viruses – the herpes virus being one. Some patients struggle with dermal issues such as Morgellons and various rashes.Third, nearly all patients suffer with inflammation & pain. Pain, pain, pain and more pain. Fourth, DMSO is a strong anti-oxidant and powerful free radical scavenger. Both are helpful for immune health and fighting pathogens. Fifth, DMSO is known as the “Supreme detoxifier,” and assists in heavy metal detoxification. If patients can’t detox all they are killing, they will not improve. For more on this important issue: https://madisonarealymesupportgroup.com/2015/08/15/herxheimer-die-off-reaction-explained/
Fischer has a section in his book about DMSO usage and Lyme. He, unlike the CDC/IDSA/NIH, acknowledges that the borrelia bacteria is very persistent and that standard treatment is either very long and/or mostly unsuccessful. He recommends a combination of an oxidative bactericide(MMS, MMS2, or hydrogen peroxide)and DMSO as a carrier to ensure penetration into the favorite hiding places of borrelia as well as deals with the various forms and stages of the pathogen. DMSO is an excellent detoxifier which is a boon for eliminating the endotoxins caused by borrelia when it is destroyed. This last element is just as important as killing organisms as the die-off can make patients miserable and cause significant symptoms. Whatever bactericide is used needs to be pure as DMSO will take it directly into the body.
IF your brain works like mine you are thinking, “If DMSO is such a great carrier, why don’t we use this with antibiotics to make them more effective?” Great question. Ask your doctor. It could also be said that it could take essential oils into the body as well….. See where this is going? It also penetrates the blood, brain barrier.
While Fischer recommends combining DMSO with an oxidizer for Lyme, DMSO alone is bacteriostatic, antiviral, and antifungal. Between 30-40% aqueous solutions have inhibited the growth of Pseudomonas, Staphylococcus aureus, and Escherichia coli. Other tests have proven diluted DMSO fight bacteria, viruses, and fungi and improves distribution of other antimicrobial substances and enhances their effects.
Last but not least, I highly recommend holistic health practitioner Amandha Vollmer’s video on using DMSO on the skin and for scarring:https://yummy.doctor/video-list/dmso-for-wounds-and-scars/ This will be my next experiment to hopefully resolve the pulling of the skin.
Video Summary(Approx. 16 Min):
DMSO can completely erase scars (or at least minimize them)
DMSO can work on stretch marks from weight loss or pregnancy
She recommends less than a 40% DMSO solution for skin use (particularly if the skin is above the waist – but it really depends upon your tolerance. Take care red heads and blonds as your skin is more sensitive)
DMSO is transdermal, and a penetrating agent which is able to deliver nutrients to tissues
She has a product called “DMSO with added nutrients”. It contains reduced DMSO with aloe vera and with 1-3% of essential nutrients which includes iodine, vitamin C, MSM, B complex, buffered C, magnesium, and rose geranium flower water
Make sure you are getting adequate food nutrition as that is the bedrock of healing
Coupling DMSO with other nutrients/herbs is powerful medicine as it drives it into the skin where it can be directly utilized
One other personal note: Lyme patients can struggle with hair loss. I sure do, which has led me to research healthier options than the Minoxidil products for women (which I have also used). This search led me to Amandha Vollmer’s helpful book: “Healing With DMSO.” In it, I learned of a hair growth/scalp care spray which consists of:
at least a 100ml glass spray bottle with a cap (I recommend capping the solution in between uses rather than leaving the plastic spray attachment in the solution. When I purchased a dropper bottle, all the DMSO managed to evaporate over the years I had it, whereas a cap would have prevented this. Have a separate dropper you can use for application if needed)
50ml (1.7oz) of 99.9% pharmaceutical grade DMSO
20ml (.7 oz) preservative free aloe vera juice
30ml (1.1) distilled water
6 drops 100% pure rosemary essential oil
4 drops of 100% pure peppermint essential oil
Spray on dry, clean hair 1-2 times a day. May take a year of usage before results are seen.
This find sent me on another search for homemade shampoo as anything put on the hair will go systemically into the body with the DMSO. I experimented until I found:
1/4 C coconut milk (homemade or canned)
1/4 C pure castile soap
20 drops essential oils (peppermint, lavender, rosemary, or orange are good)
Combine all the ingredients in an old shampoo bottle or jar
Shake well to mix & each time you use (only need about a tsp)
Keep in the shower for up to a month
a 50/50 mixture of apple cider vinegar & water is a good rinse as well
To make your own coconut milk:
4 C filtered or distilled water
2 C unsweetened shredded coconut
Heat water until hot/not boiling
put water and coconut into a Vitamix and blend on high for a few minutes until thick
pour through mesh strainer and squeeze through cheese cloth if needed. Essentially, you only want the milk, not the fiber (keep and use fiber in your smoothies)
use required amount for the homemade shampoo and drink the rest (will keep for 5 days in refrigerator for drinking)
I used the shampoo/DMSO spray combo for a while after I had tried the Rogaine product. I did not lose any hair on the experiment but got a perm and discontinued until all the chemical has been eliminated from my scalp.
UPDATE Oct. 2024: I’m sorry to say the DMSO for hair growth did not work for me. I hope you have better results. The shampoo was effective but it must be refrigerated as it is all natural and will spoil.
Safety:
DMSO has a LD50 value and is safer than ibuprofen, aspirin, caffeine, and cooking salt! Study after study has proven its safety record on both animals and humans.
https://www.sott.net/article/228453-DMSO-The-Real-Miracle-Solution If you search for DMSO on the U.S. National Library of Medicine (pubmed.gov), you’ll get almost 30,000 indexed results, making it one of the most studied compounds of our time. Yet, we are led to believe that DMSO can’t pass the required regulations for its approval in other medical conditions even though its effectiveness and low toxicity profile is unquestionable.
The above link also completely refutes a 1960 animal study that DMSO caused eye lens trouble. In fact:
As far as eyes are concerned, the evidence on DMSO is quite to the contrary. When several patients treated with DMSO for muscular problems reported to Dr. Jacob that their vision had improved, he sent them to Dr. Robert O. Hill, ophthalmologist at the University of Oregon Medical School. Confirming the favorable changes, Dr. Hill began his own experiments with DMSO (after it was known that the lens changes did not happen in humans). His research showed drops of 50% DMSO to be effective in retinitis pigmentosa and macular degeneration, and presented a report on this at the New York Academy of Sciences symposium in 1971. (Haley, 2000)
Dimethyl sulfoxide caused teratogenic responses in animals when administered intraperitoneally at high doses. Oral doses did not cause problems of reproduction in animals. In one study topical doses produced terata in animals, but in another study topical dose failed to produce any abnormalities. There are no controlled data in human pregnancy. FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
Contraindications: According to Jacob in “The Miracle of MSM The Natural Solution For Pain,”DMSO has been found to counteract platelet aggregation. He advises caution for those taking blood thinning agents such as heparin, aspirin, or dicumarol. Accelerated blood thinning can not be ruled out. Indications that that is occurring would be bruising or increased bleeding from hemorrhoids.
Now for the tricky part…….
When applied externally DMSO opens capillaries. This can lead to temporary redness of the skin. It can also burn and itch. Evidently, not everyone experiences this but I did. To me it felt a lot like taking niacin. Wowza, but worth it.
DO NOT ITCH
The reduction in pain and swelling will be dramatic. It’s worth the initial discomfort. For me existing pain went away in seconds. Other patients have told me it took a number of days for noticeable improvement.
The next tricky part is understanding how DMSO breaks down into components. Most of the DMSO will be broken down to MSM in the body; however, there is a small part (about 1%) that breaks down into a substance that causes a temporary odor. Some say it smells like garlic. I say it smells like oysters.
The viscosity of DMSO is double that of water which means it drips off the skin easily which is why many like gels and lotions; however, Fischer cautions that gels/lotions are made from raw materials such as polyacrylic acid derivatives which will be taken directly into the body. He recommends the pure DMSO liquid that will take a tad longer to be absorbed than the lotions. If you choose gels or creams make sure you are confident about ALL the ingredients as they will go directly into your body. Please keep this in mind. Essential oils, antibiotics, anything applied with DMSO needs to be PURE. Also, many EO’s can cause skin irritation so you need to work with a knowledgable practitioner. I include a recipe on how to make your own DMSO gel a bit further down in the article.
And that’s another point that needs to be made. DMSO MUST COMPLETELY DRY before anything touches it. Again, because DMSO is a solvent/carrier, it will take everything and anything directly into your body such as perfumes, dyes, germs, etc. So application must be done over an unbleached white towel, with clean hands and instruments and allowed to completely dry before covering with clothing or anything else. Also note what the DMSO is stored in. I would only get DMSO stored in glass as immune disruptors in plastics can leach into your body.
The next tricky part: Just like you will find detractors for DMSO, you will find detractors on MMS and the other oxidizers Fischer recommends for Lyme/MSIDS. This is where you need to do your own research, talk to plenty of health professionals and make up your own mind. Perhaps I’ll take on the subject of oxidizers in another article, but for now I’m just going to cover DMSO and MSM.
In essence, between the fact it does so many things which would interfere with the sale of many other drugs, and the fact it smells a bit, which makes it virtually impossible to complete double blind studies as the smell would give it away, big pharma tossed it to the sidelines. But read the article for yourself as there’s great info in it, including what it can do for you.
**Update on smell** Recently I applied the pain gel on a larger area on my husband a couple times a day for a few days (listed below) on my husband. Our kids stated, “What’s that old lettuce-like smell?” After searching throughout the house we figured out it was my husband. So it’s not horrible but it’s noticeable and if you are in a cramped office space, trust me, they’ll smell it. But, desperate times turn to desperate measures, right?
DMSO is generally applied to the skin in a gel, cream, or liquid. It can be taken by mouth or as an intravenous injection, in many cases along with other drugs. It has also been administered subcutaneously, intramuscularly, intraperitoneally, intrathecally, by inhalation, instilled into the eye, on the mucous membranes, and into the urinary bladder. Strengths and dosages vary widely.
If you are just dealing with pain or an injury, use a topical application. Don’t drink it. Drinking it is for serious detoxing and other internal necessities. If you use a rose scented DMSO cream, chances are that nobody will be able to smell DMSO’s garlic-like smell. (My comment: Be careful here – unless you know for certain that smell came from a pure source, don’t use it. I called this company and heard nothing back which says everything to me. I won’t be using the rose cream!)
The usual oral dose of DMSO is one teaspoon per day of DMSO 70% (Morton, 1993). But since it can trigger detoxification reactions and DMSO’s total excretion from the body can take several days, it is best to do it only once a week to begin with. Start with half a teaspoon of DMSO 50% and increase to a teaspoon of DMSO 70% only if any possible detoxification reaction is well tolerated.
When you use liquid DMSO in the skin, let it dry for over 20 to 30 minutes before wiping the rest out (with an unbleached white towel). The skin must be clean, dry, and unbroken for any topical use of DMSO. The face and the neck are more sensitive to DMSO and no higher concenrations than 50% should be applied there. Topical concentrations of DMSO should be kept below 70% in areas where there is a reduction of circulation. When 60 to 90% DMSO is applied to the skin, warmth, redness, itching, and somtimes local hives may occur. This usually disappears within a couple of hours and using natural aloe vera, gel or cream, will help counteract or prevent this effect. When 60 to 90% DMSO is applied to the palm on the hand, the skin may wrinkle and stay that way for several days.
Chronic pain patients often have to apply the substance for 6 weeks before a change occurs, but many report relief to a degree that had not been able to obtain from any other source. In general, the greater the chronicity of the disorder, the longer the treatment with DMSO must be employed in order to achieve palliation (Steinberg , 1967).
Common health problems for which people will apply topical DMSO at home include acute musculoskeletal injuries and inflammations. The earlier DMSO is used, the more dramatic the result. A 70% concentration of DMSO mixed with water in volumes ranging from 8 to 12 ml, applied on and around the injury in a wide area at least three times daily, will have a healing affect in 4 out out 5 people.
Arthritis, Sprains, Strains
It provides rapid amelioration of pain and increased mobility and reduction of inflammation when used topically. You can see a positive response within 5 to 20 minutes and usually lasting for 4 to 6 hours. (Steinberg, 1967).
Topical
You can make your own gel: (make sure hands, utensils, and body are completely clean)
http://organicbiomama.com/dmso-safety-handling-recipes Mix 1oz70% pure DMSO and 3 oz Aloe Vera gel(at least 99.5% pure) in a glass container & store in a cool place. It’s best to mix right before application. I like this idea much better than the creams/gels on the market with questionable preservatives.
**For my personal recipe that has been used successfully for pain, please continue reading as it’s in the MSM section as MSM is one of the ingredients**
I include this video to show there are DMSO creams on the market; however, I am concerned about it being stored in plastic as well as the added ingredients such as perfumes and dyes as they will go directly into the body.
Oral
According to Fischer in the DMSO handbook, due to the long half-life of DMSO, levels increase as you continue taking it. Fischer recommends starting at a low dose of 3.5g (1 tsp = roughly 3ml) in a glass of water and to observe symptoms. If pain is relieved and it is well tolerated, remain at that low dose. If not, he recommends increasing in increments of 3.5g per day.
Interactions: DMSO has been found in studies to counteract platelet aggregation. If you are taking blood thinners, please consult your physician before starting DMSO.
Oral directions:
Pour 3.5g DMSO into clean glass (about 300ml or 10 oz)
Fill with water or chosen drink (DMSO releases histamines from body cells so he advises against tomato juice, but that cooled tea, or grape juice work well) DMSO is bitter in water so some prefer something to mask it. I say “tough it out” and use water. You don’t need all that added sugar.
Mix well as DMSO will sink to bottom of glass
This gives you a 1-2% DMSO solution
Many find doing this after breakfast agreeable
DMSO has a diuretic effect. Taking before bed is not advisable unless you like to get up to go to the bathroom a lot!
3.5ml of DMSO at a density of 1.1 g/ml is equal to 3.85g giving you a dose of about .05g DMSO per kilogram of body weight if you weigh 75kg. This is a long way from quantities that are labeled as clinically safe in most clinical trials and toxicity tests.
There is no promise of a cure; however, and there are some “non-responders.” And of course, it’s important to work on all aspects of health such as proper rest/sleep, nutrition, exercise, stress reduction, addressing hormonal, nutritional, mineral, and emotional imbalances.
Dimethyl sulfoxide exits the body in about 24 hours. Nevertheless, in both acute and chronic cases, it is recommended that you take some time off on a regular basis, say two days in a row each week. For example, just take Saturday and Sunday off every week. If you are using it daily, long term, take two to four weeks off, in a row, every six months. Or, you could do 30 days on and 30 days off.
Personal usage: I have personally used a 70% DMSO gel purchased on-line topically myself as well as on numerous Guinea pigs – i.e., my family. Once we got past the initial redness, burning, and desire to itch, pain & swelling reduced within minutes. Dr. Jacob states this pain reduction lasts for 4-6 hours and that was our experience as well. The smell of oysters in this case was very mild as the amount of DMSO used was small. My LLMD has used IV DMSO and states that really smells – but the results were worth it.
My favorite way to use DMSO is the 70% strength liquid that is stored in amber glass. This is the brand I use. I will take a dropper (does NOT come with the bottle but has a black cap) and simply drop on area I wish to treat. I then either take clean fingers and slightly smear it over area or use a clean cotton ball. To dry it quickly, put area in front of a fan so air circulates and it evaporates more quickly.
I have not taken DMSO orally, however I know a patient who did. When he came to group meeting there was a noticeable but tolerable kind of garlicky/oyster smell.
MSM
Before you try DMSO you may want to try MSM first as it is devoid of the odor, and doesn’t cause redness and itching when used topically. Since it worked so well for me (as well as numerous other patients) I never have had to even take DMSO internally. I have only used it topically when I’ve had specific pain and it worked like a charm. Using DMSO topically will also yield less odor. If you use at night before bed, odor should be gone by morning.
MSM stands for Methylsulfonylmethane and is a naturally occurring sulfur compound which is 34% sulfur by weight and is a metabolite of DMSO. It is a dietary mineral element that is an odorless, white crystalline powder that is somewhat bitter tasting. It was approved as a Generally Recognized As Safe (GRAS) substance in 2007 and is well-tolerated by most.
MSM is produced naturally as part of the Earth’s sulfur cycle involving algae, phytoplankton, and marine organisms, where it is absorbed into the soil, taken up by plants or soil bacterium and is expressed in minute amounts in many fruits, vegetables (broccoli, cauliflower, cabbage, garlic, onions), coconut & olive oil, eggs, pasture-fed meats, and grains. It is destroyed when pasteurized or heated at high temperatures and is also volatile when frozen or irradiated.
It’s synthetically produced through the oxidation of DMSO with hydrogen peroxide and then purified via crystallization or the preferred method of distillation which particular method yields no detectable differences from the naturally produced product. The synthetic method allows patients to ingest far more than possible through food alone.
According to Stephanie Seneff PhD for the Weston Price Foundation,
“Sulfur is the eighth most common element by mass in the human body, behind oxygen, carbon, hydrogen, nitrogen, calcium, phosphorus and potassium. The two sulfur-containing amino acids, methionine and cysteine, play essential physiological roles throughout the body. However, sulfur has been consistently overlooked by those addressing the issues of nutritional deficiencies. In fact, the National Academy of Sciences has not even assigned a minimum daily requirement (MDR) for sulfur…..
Experts have recently become aware that sulfur depletion in the soil creates a serious deficiency for plants,17 brought about in part by improved efficiency in the U.S. agricultural industry, which has steadily consolidated into highly technologized mega-farms.
It is estimated that humans obtain about ten percent of their sulfur supply from drinking water. Remarkably, people who drink soft water have an increased risk of heart disease compared to people who drink hard water.2 Many possible reasons have been suggested for why this might be true, and just about every trace metal has been considered as a possibility.3 However, I believe that the real reason may simply be that hard water is more likely to contain sulfur….
I recently came upon a remarkable article in a 1997 issue of FASEB11 which develops a persuasive theory that low blood serum levels of two sulfur-containing molecules are a characteristic feature of a number of disease conditions. All of these diseases are associated with muscle wasting, despite adequate nutrition. The authors have coined the term “low CG syndrome” to represent this observed profile, where “CG” stands for the amino acid “cysteine,” and the tripeptide “glutathione,” both of which contain a sulfhydryl radical “-S-H” that is essential to their function. Glutathione is synthesized from the amino acids cysteine, glutamate and glycine, and glutamate deficiency figures into the disease process as well, as I will discuss later.
The list of disease conditions associated with low CG syndrome is surprising and very revealing: HIV infection, cancer, major injuries, sepsis (blood poisoning), Crohn’s disease (irritable bowel syndrome), ulcerative colitis, chronic fatigue syndrome and athletic over-training….
In summary, a number of different arguments lead to the hypothesis that sulfur deficiency causes the liver to shift from producing cholesterol sulfate to producing arginine (and subsequently nitric oxide). This leaves the intestines and muscle cells vulnerable to oxidation damage, which can explain both the intestinal inflammation and the muscle wasting associated with Crohn’s disease.”
Doctors Jacob, Lawrence, and Zucker in their book “The Miracle of MSM – The Natural Solution for Pain,” explain thatSulfur is necessary for the proper formation of proteins and helps produce amino acids, connective tissue, enzymes and hormones. And that sulfur insufficiency is probably related to many disease states – perhaps including Lyme/MSIDS.
It all stems back to the 70’s when chemists from Crown Zellerback Corp, and doctors Herschler and Jacob of Oregon Health and Science University experimented with MSM to determine if it had similar therapeutic uses to DMSO. In 1981 Herschler obtained a patient to use MSM for skin, nails, and as a blood diluent. There were further patents claiming to relieve stress, pain, treat parasitic infections, increase energy, boost metabolism, enhance circulation and improve wound healing, despite little scientific proof. Current research has shown proven clinical improvement in arthritis, inflammatory disorders like interstitial cystitis, allergic rhinitis, and acute exercise-induced inflammation.
Both DMSO and MSM get into tissue due to their small size.
The clinical use of sulfur as an adjunct in our diet is becoming progressively more recognized as an important tool for optimizing health. MSM is already well-known for its joint health benefits, but may also be helpful for other conditions related to chronic inflammation and damage due to oxidation
MSM, which is a metabolite of DMSO approved for use in humans, primarily impacts your health by reducing inflammation. It’s widely used as a supplement for arthritic conditions. Like DMSO, MSM also appears to improve cell wall permeability, so it can be used to help deliver other active ingredients
MSM may be providing a missing link for optimal health, which appears to be related to sulfur. It also affects sulfur metabolism in the human body, although it’s still not entirely clear how
Sulfur also plays a critical role in detoxification, as it is part of one of the most important antioxidants that your body produces: glutathione. Without sulfur, glutathione cannot work
Toxicity studies have shown that MSM is extremely safe and can be taken at very high doses. Even if you have a very rich diet full of raw vegetables and MSM-rich foods, you can still supplement and not hit that toxicity level. Clinical research studies have found that the effective amounts range from about 1.5 grams to 6 grams
*Reduces cytokines & inflammation(in vitro studies show MSM reduces IL-6 (a marker implicated in chronic inflammation as well as suppressing NO and prostanoids) *antioxidant *free radical scavenger *kills gastrointestinal, liver, and colon cancer cells *restored normal cellular metabolism in mouse breast cancer and melanoma cells *helps wounds heal *increases blood flow *reduces muscle spasms*antiparasitic properties(especially for giardia) *normalizes the immune system *cholinesterase inhibitor *alleviates allergy symptoms *increases energy *improves condition of hair, nails, and skin
Karlene Karst, registered dietician, gives a 3.5 Min supplement review on MSM.
Like DMSO, MSM is more of a therapeutic principle than a drug and seems to be providing some kind of missing link within the body.
Safety
Toxicity studies have shown that MSM is extremely safe and can be taken at very, very high doses. Even if you have a very rich diet full of raw vegetables and MSM-rich foods, you can still supplement and not hit toxicity. Clinical research studies have found that the effective amounts range from about 1.5 grams to 6 grams, although at higher doses, potential side effects include:
Intestinal discomfort
Swelling of the ankles
Mild skin rashes
These are likely detoxifying effects that can typically be mitigated or minimized by cutting back on the initial dosage, and slowly working your way up. In that case, you might want to start out with half a gram (500 milligrams) for a couple of weeks and then slowly increase until you get up to the desired dose.
Pregnancy:https://www.drugs.com/npp/methylsulfonylmethane-msm.html Information regarding safety and efficacy in pregnancy and lactation in humans is lacking; however, according to the MSM book by Jacob, he states, “Clinical experience indicates MSM is safe for pregnant women. We recommend; however, that you consult first with your physician before taking this or any other supplement or mediation.” (p. 47)
Regarding children: Jacob states that healthy children do not usually need MSM; however, those with allergies, asthma, or an inflammatory illness should consider using it. He also states many kids have taken MSM – some in high amounts without problem.
Contraindications: While DMSO has been found to counteract platelet aggregation, MSM has not been similarly tested in studies; however, clinical observations indicate it may also have a blood-thinning, aspirin-like effect. Discuss MSM supplementation with your doctor before taking it.
MSM & blood tests: Dr. Jacob recommends stopping MSM before a liver function test as it may interfere with the accuracy of the test and produce a false positive. Resume supplementation after the test.
How to Select a High–Quality MSM Supplement
There are two methods of purification of MSM:
Distillation
Crystallization
For MSM, distillation is by far superior. But crystallization is less expensive, and a lot less energy-intensive. According to Dr. Benjamin, only two companies that produce MSM use distillation. Mr. Benjamin explains why you should consider a product that has been purified using distillation.
“A lot of the problems with [crystallization] is you’re essentially crystallizing it out of a parent solvent or liquid. If there are any impurities, which could be salts of heavy metals, you could have aromatic hydrocarbons in that… It’s actually the parent solvent. It’s usually water. It is dependent upon water quality.”
I recently posted this: https://madisonarealymesupportgroup.com/2018/01/03/the-invisible-universe-of-the-human-microbiome-msm/Lyn-Genet Recitas, NMT, Sports Nutritionist, Holistic Health Pracitioner, RYT, and author of “The Plan,” calls MSM the wonder supplement for your gut. It can alleviate allergy symptoms, helps with detoxification, eliminates free radicals, and improves cell permeability. She states that with given time, MSM will start to actually repair damage caused by leaky gut – a common problem with Lyme/MSIDS patients. It can also help the body’s ability to absorb nutrients from food. Many Lyme patients struggle with paralysis of the gut where the muscles of the stomach and intestines stop being efficient. MSM helps this muscle tone as well.
Similar to DMSO you can take MSM topically and internally. It is recommended to start at a low initial dose and allow the body to acclimate. You can slowly increase the dose after a week. It is also stated that those with chronic conditions may take up to 6 or more months to notice a difference.
Topical
MSM comes in creams, gels, and lotions. Make sure you read about the other ingredients and if the MSM is made from distillation. Like any other supplement, the devil’s in the details. Recently I made my own MSM cream, which was quite easy and I loved how it worked as a skin cream as well as for a pain cream.
Get pure 100% MSM powder made by distillation. (Should have OptiMSM patent on it)
Get pure aloe vera gel (99.5% or higher)
Mix 1/2 Cup aloe vera with 1-2 Tablespoons MSM – a tiny whisk or stirring stick works best. **Update** I’ve reduced the amount of MSM in half due to the drying effects for the facial cream. Play with this amount for your own needs. The pain cream obviously has much more MSM in it – read below.
(Optional) Add your favorite pure, organic therapeutic grade essential oils – I used 3 drops lavender and 3 drops frankincense for a facial cream. Guys this is for you too. It is non greasy, tightens pores, & smells great. **Update** I switched this to a synergy blend from Plant Therapy called Zit Fighter – 6 total drops for half C aloe.
This same cream can be used for pain relief but add another tablespoon of MSM (total of 3 Tbsp). Desired EO’s include Capaiba for inflammation (3 drops), Lavender for skin conditioning (3 drops) and peppermint as a cooling and driving oil taking the MSM deeper (4 drops). Mix all well. **Update** I’ve switched this to a Plant Therapy synergy blend called Organic Rapid Relief for the pain cream – 10 drops, and I’ve added liquid DMSO – 10 drops. You can play with the amount of DMSO for your own personal preference. I’ve used this on many and they all have responded with fairly immediate pain reduction, even a person who reactivated pain from an old foot fracture. One word; however, sometimes a sheen of the white MSM crystals remain on the skin after it dries. Just brush them off once it’s dry. Also, since DMSO has been added, make sure this all dries before touching it to clothing or anything. For tougher pain, I will take the appropriate amount of pain cream in my hand & add 10 or more extra drops of DMSO. Immediately it heats up in your hand. This has almost always worked for the worst kind of pain. Of course the more DMSO you use the higher the potential for that lovely smell…..so it’s a balancing act if you are around people.
Store in glass with a tight fitting lid like a small wide mouthed mason jar in a cool, dark place. I would also make sure the level of cream is such that it doesn’t touch any part of the lid – be it plastic or metal. If it’s glass, that should be fine. But it needs to be air-tight.
Internally
If you take 2-3g a day or less, capsules are convenient. For higher doses crystals are cheaper and easier.
You should take the least amount to achieve the desired benefit. More is not necessarily better. According to the MSM book a dosage of 2g (2,000mg) is adequate; however, higher doses are often necessary to experience therapeutic effects. You may need 3-4g of MSM to control allergy symptoms and for deep-seated severe conditions, you may have to even go higher. It is also recommended to divide the dose throughout the day, but since MSM increases your energy, it’s best not to take it before bedtime.
For pain and inflammatory conditions, Jacob recommends topical and internal MSM.
Personal usage: Currently, most of my family uses MSM internally, daily – including the dog. We all started at 1/4 tsp once a day for a a few days then increased to twice a day. After that, it was individual preference. I increased to 1/2tsp twice a day and all of my pain is GONE. My husband takes 1 tsp twice a day.
Initially we simply put the crystals in a few ounces of waters, stirred it up, and drank it. Now, after reading from health practitioner Amandha Vollmer, that parasites do not like MSM, I simply dump the crystals into my mouth and then drink water, so I’m not dissolving it before hand.
My daughter struggles with Mast Cell issues and this has helped her a lot. As you read it reduces or eliminates allergy symptoms and for her it has reduced mucus production and has boosted her immune system as well.
I’ve used a manufactured MSM cream with glucosamine chondroitin in it; however, it does have the caprylic ingredient along with parabens and other nasty ingredients Fischer warns about so I won’t be purchasing more, just making my own. I will say it worked for pain – within minutes.
Update: I’ve been taking the MSM internally for months now with complete resolution of pain. The only negative side-effect I had was my skin broke out due to the strong detoxification effects. I broke out on my face, chest, and back just like a teenager. Due to that I lowered the MSM to about half of what I took to give my body some help in clearing debris. Within a couple of weeks that went away and I upped my dose back to 1/4tsp twice a day. The pain never returned. Please know this has been miraculous as nothing else has worked.
**Progress update** After a year or longer we are back on antibiotics as numerous symptoms came back. This demonstrates once again the need to remain open-minded and adjust to the curve balls in life. For us it’s pain in the C7 with accompanying occipital pain (right in the juncture between the base of the skull & the neck), stiffness of the spine, painful bottoms of the feet, migrating pain sometimes affecting the hip and/or other areas, as well as pain in the center of the palm (think crucifixion). These are all past symptoms popping back up and and the body never forgets cellular memory! It appears we are still dealing with Lyme (borrelia) and Bartonella.**
**UPDATE Feb. 2022**
After developing a Baker’s cyst which is extremely painful and debilitating, I’ve been sleuthing yet again for relief. I plan on writing a separate article on what I’ve been learning and it is revolutionary – niacinamide and vitamin C for arthritis. For now, if you want to study it yourself, go to Dr. Saul’s website and read the wonderful accumulation of articles there: http://www.doctoryourself.com/, specifically:
All I can say is those with you suffering from arthritis and the pain it causes, you owe it to yourself to learn about niacin, niacinamide, and vitamin C therapy. It’s a game changer.
Depending upon your goals, if your doctor gives you a thumbs up, I would try MSM first as it is easy to obtain and has no side-effects or smell. If the MSM works (primarily for pain, inflammation, detox, & leaky gut) then you are home-free. If it doesn’t, you may want to then move on to get the OK from your doctor to try DMSO as it demands more knowledge, effort, attention to detail, and has a smell, depending upon amount used. FYI: I have never noticed the smell for the amount used topically in my recipes. For those who desire to try DMSO and an oxidative bactericide for a full Lyme/MSIDS treatment, please work under the direct supervision of a practitioner.
And remember what your granny told you: “Necessity is the mother in invention.”
And finally, after reading my last update, never feel badly about needing to return to anti-microbial treatment, be it antibiotics or others. This is the nature of this beast. It is persistent, it is stealthy, and it is tenacious. You and I need to decide we are stronger and do what is necessary to get back on top.
Madison Area Lyme Support Group 