Lyme disease, science, and society: Camp Other
Showing posts with label collateral effects. Show all posts
Showing posts with label collateral effects. Show all posts

Saturday, April 14, 2012

6 Commentary: On Dr. Phil, Lyme Disease, And "Faking It".

Yesterday a segment about chronic Lyme disease aired on the Dr. Phil Show. There's been much discussion about this episode online throughout the Lyme disease patient community, and so far comments by the hundreds have been posted rapid fire to Dr. Phil's web site about chronic Lyme disease.

I am in support of seeing more coverage on Lyme disease and patients with persisting symptoms, but I am not in support of seeing the angle of hypochrondria or "faking disease" being mentioned - even in passing - in relationship to Lyme disease.

The issue of whether or not a patient is faking their symptoms came up during an interview with a 25 year old model, Stephanie, who is experiencing unusual attacks and symptoms - and who has been accused of behaving this way in order to get attention.

While I do not know all the details of Stephanie's medical history, I would be one of the last people to accuse her of faking her symptoms to get attention. I say this in part because if she has suffered with these symptoms for five years* and hasn't been getting out much due to her condition - then like myself, she's probably discovered that after that period of time other people will stop inviting you to events. Some may not even visit.

Being a model equates with an active social life, attending events, and self-promotion. Getting plenty of attention lands you work. Becoming sick and spending most of your time at home kills your career and leads to isolation. There is little to gain there, and any initial sympathy which might be gained wears thin after the first several months. People will move on without you.

Having suffered the personal costs of isolation due to chronic illness myself, I have sympathy for her situation. And I am appalled that the first thing Dr. Phil would ask was not what evidence she had that she was suffering from Lyme disease - but to ask whether or not she was faking her symptoms.

While I disagreed with her method of self medicating, it is clear to me that she has been suffering. I've never experienced what she is calling seizures - however, earlier in my illness I had episodic attacks of severe pain which would cause me to curl up, wince, and yell with pain.

The pain was so intense there was nothing else I could do. It often happened when I was alone in bed and everyone else was out of the house. If someone wanted to accuse me of a payoff for my behavior, it wasn't coming.

It seems to be a running theme over time - this concept that if one is ill with a condition that is not easily understood or for which tests have not been well developed - then somehow the patient's symptoms must be "all in their head," or the patient must be "making it all up".

And that if a patient behaves in an unusual manner, accusations fly that they must be acting out, with others suggesting that "perhaps they have a psychological problem," or  "perhaps they just want attention."

I can't think of how many times I've heard these statements made about someone with certain medical conditions - usually conditions where the person physically appears normal to others at least some portion of the time, and isn't showing an overt sign of illness or injury.

Patients with a broken leg or weeping sores are not accused of hypochrondria or of "faking it". When a physical symptom is a daily constant and is taking time to heal, it's a concrete visual reminder to others that a person is not well.

But if someone has lesions on their brain, only their radiologist who took the MRI saw it. No one else can see them.

If someone has extreme fatigue, only they know what the experience is like to be feeling the heavy weight of that burden on their body all the time - while everyone else just sees them as someone who lies on a sofa or in bed all day and might judge them as being lazy.

If someone winces in pain at someone else turning on a lamp or children talking and laughing animatedly, everyone else may see them as being overly sensitive without knowing the experience of the person for whom sounds seem three times louder and light five times brighter.

People understand what they themselves have experienced, and people understand what they can see. Many people joke about using the Missouri license plate motto as their own personal mantra: Show me. They don't believe in something's existence unless they can see it or experience it firsthand.

But anyone with an ounce of scientific reasoning and logic can see that just because one cannot see something or experience it firsthand does not mean it doesn't exist. One can detect the presence of some agent or phenomenon through indirect detection. Much like antibodies in a blood test, one can determine infection is present without detecting the causative organism itself.

In the mid-1800s, doctors and others believed that patients' exposure to bad air in hospitals are what lead to infection in wounds. Washrooms for doctors' hands and patients' wounds were not available. Washing hands before seeing a patient was not considered necessary to avoid infection - the idea never entered one's mind.

One doctor, Dr. Joseph Lister, learned about Louis Pasteur's research that rotting and fermentation could occur under anaerobic conditions if microbes were present. By learning more about Pasteur's hypothesis as to what could prevent rotting and how this might apply to infections, Lister decided to conduct his own experiments. Even though he could not see the microbes themselves he could see the results of his research: antiseptics prevented infections in wounds fron taking hold.  

Lister went on to encourage doctors he supervised to wash their hands before surgery and use antiseptics - even though at the time doctors thought it was unnecessary and a joke at first. Nonetheless,  as time went on, others began to adopt his practices and went on to prevent many cases of infection and sepsis.

For centuries, scientists hypothesized that extrasolar planets existed. But it is difficult to directly detect them. Most extrasolar planets are detected through indirect detection methods such as measuring radial velocity or the Doppler method, by observing the drop in brightness emitted by a distant star due to a planet's transit in front of its disk, and by using several other methods. In astronomy, one can observe a number of planetary bodies' presence through the use of inference. By looking at different stars, we can infer something about the planets orbiting them - even if we can't see the planets with our own naked eye - or in some cases, even with a telescope.

These are just two examples where inference leads to association and discovery.

But here we are, in 2012, and it seems that the power of inference is somehow broken in doctors and neighbors who leap to the conclusion about patients who have symptoms they do not understand or which they have trouble offering an official diagnosis.

Like the doctors who believed patients were getting infections from bad air in the hospital without any particular data to support their conclusion - some doctors today are making snap judgments that patients' symptoms are due to their own neurotic imaginings.

The truth is, it might not be that easily determined why it is some patients are having the symptoms they do.

Instead of saying these three words, "I don't know," when there is no quick answer as to why a patient has particular symptoms, some doctors readily fall back on a psychological cause. Often without any particular training in psychology. Often without any psychological and neurological testing of the patient in front of them. Often without any rule-outs to determine if some underlying medical condition could be contributing to their patient's symptoms.

And sometimes, even with training, there is a risk their diagnosis is wrong. Because if one doctor looks through the same lens of his own area of specialization every day, sometimes it's difficult to consider presentations from a different angle.

While the debate about the cause continues, the recent outbreak of a strange rash of illnesses in upstate LeRoy, New York, could be one example of making a snap judgment based on a psychological condition.

A group of young women (and as it turned out later, one young man who didn't know them) in high school began exhibiting strange behavior last year. They have had unusual tics and verbal outbursts similar to those found in Tourette's syndrome.

They were taken to various medical professionals to be interviewed and examined, and the initial diagnosis which was offered was "conversion disorder". Conversion disorder used to be previously known as "hysteria", and before Freud used the term, hysteria was associated with people who were malingerers, had weak nerves, or had some meaningless disturbances. No reason for these behaviors was ever given back then beyond having poor character or a weak constitution.

Today, conversion disorder is not the same thing. It's not thought to be due to malingering or feigning illness - it is a genuine psychiatric disorder which is not related to any underlying neurological or infectious cause and is rooted in extreme stress and anxiety. One could argue it is a physiological and biochemical response to stress.

But given its psychological origins, some parents disagreed with this diagnosis outright - and feeling that their own kids could not have this disorder, they sought second opinions. With further investigation into biological causes for their symptoms, one doctor diagnosed a young woman in neighboring Corinth, New York, with Lyme disease and is apparently evaluating some of the students from LeRoy.

Today, months after the original outbreak, debate over what exactly is the cause of all these students' unusual symptoms has continued. One physician who treated some of the girls classified the disorder as PANDAS, related to streptococcal virus. Some of the girls got better under treatment for PANDAS. Some have not. Some doctors do not even think all the students suffer from the same condition as their individual presentations are somewhat different.

Where can anyone rest with this, with the knowledge that people that exhibit unusual behavior may not have it "all in their heads" and are not "making it up"?  And that similar symptoms might stem from different causes?

One must appreciate that sometimes it takes time to sleuth out the proper diagnosis. But one must also begin to appreciate that it is way past time to stop discriminating against people and labeling their motives and essential character as human beings if they engage in unusual behavior - whether it began with a traumatic experience or a tick bite.

Even if it turns out some of these young women have a disorder which was triggered by extreme stress, that does not mean they are faking it. It would be a genuine medical problem that requires treatment, just as PANDAS and Lyme disease need treatment.

From the infectious disease angle, this is not the only item to hit the news in recent months which brought up discussion about the possible relationship between bacteria and behavior.

Researcher Jaroslav Flegr has been investigating the relationship between infection with toxoplasmosis in people and their behavior, and already found some significant relationships. The psychological symptoms caused by toxoplasmosis are usually more subtle, so far, than what has been observed in these young women with tics and vocalizations - but they are further evidence that it is not always going to be clear if we alone are driving our behavior - or if a visiting microbe onboard is.

Other mental illnesses have been investigated for an infectious cause, such as schizophrenia - and various viruses and microbes have been implicated in or associated with its development.

Regardless of whether one diagnoses a patient with a psychological disorder or a physical condition, all of this should make us stop for a moment and think about how we as a society think about mental and physical illness in this country:  The gap between what is a biologically-based illness and what is a psychologically-based illness is closing and becoming blurred. With this change, greater acceptance and understanding of those with symptoms which affect them cognitively, neurologically, and psychologically is bound to occur.

It's been a long slow climb to work to remove the stigma that comes with mental illness in the United States. And it continues in part because of a tendency to believe that everyone has control over their own behavior. Tied very intimately to that idea is a belief that everyone has control over their bodies as well. Which is nice and a comforting thought to have, and most people who are completely healthy live with the privilege of this experience without ever experiencing anything else.

But once you have become incredibly ill, it becomes clear just how much is not under one's control. If you get into a car accident and have a spinal injury that is obvious to everyone, no one can ever tell you how long it will take to completely heal from your injury. Often it isn't clear if you'll completely heal at all.

The same applies to people who have been affected mentally - and not by choice, any more than the person who injures their spine in an accident. People who were healthy and "had it all together" can fall victim to an infection, genetic and environmental factors, temporary or permanent side effects of prescription medication, a car accident, or other traumas which leave them both physically and mentally affected.

The results are not something that is "all in their head" - if that phrase is meant to apply to an idea of them imagining it. On the contrary, having an infection or trauma which affects your brain is literally "all in your head" - and is in no way, shape, or form, imagining it. It is a harsh reality one must live with every day. It will mean not having control over your behavior and reactions to certain stimuli such as noise, light, the sense of touch, music, scents, the taste of certain foods, and then some.

To the outside observer, these reactions may seem strange. And even by the person having them, they are, and they are often aware their own reactions are atypical. But to the person who is living with them, it is what they have to live with and work around.

Antibiotics or other medications may bring their reactions under control and help. It may make life more predictable for those affected and those close to them who witness their behavior. And if anything, people who observe the change which occurs under such treatment over time should grasp that their symptoms have been due to their being ill and not because they were trying to get attention.

In regards to the practice of telling patients that a condition is imaginary, I have hoped that by 2012 we would have gotten much further by now and stopped this practice.  That we wouldn't be seeing young women in the prime of their lives with careers and hopes for the future lose all that and be told that their symptoms are only about trying to get attention by being sick.

It reminds me of stories of doctors who accused women back in the late 1800's of suffering from "hysteria" when they may have had multiple sclerosis. It reminds me of stories of doctors who accused patients in the 1980's through the present that it was "all in their heads" when they have CFS/ME. It reminds me of stories of doctors who today are saying those with chronic Lyme disease are "faking it" and aren't really sick - or perhaps they are depressed.

No doubt, depression can be a serious and debilitating condition in its own right which requires medical treatment and cannot be solved just by pulling oneself up by one's own bootstraps. We've moved beyond some of the stigma attached to depression and understand today that it is not a sign of poor character or laziness. But let's be sure to not confuse one disease or condition with another just because some of their symptoms overlap.

All this said, it is clear to me after having done extensive research on Lyme disease that everyone who has persisting symptoms related to Lyme disease after a tick bite and its initial treatment is not well. It's not "all in our heads"- even if for some of us the damage may be literally in our heads.

Lyme disease affects each of us somewhat differently - some of us have more neurological, cognitive, and/or psychological manifestations of disease than others. Given the pathogenesis of this disease, these differences should be no surprise: without early treatment during the acute stage, Borrelia bacteria disseminates throughout the body and can affect different organs and tissues - and at times, affects the nervous system, too.

Even if one does not believe in a model of chronic infection after initial antibiotic use, there is no reason to doubt that someone affected by this disease would have some damage done by its presence. This damage can lead to all kinds of problems of varying frequency and duration - damage which doctors should be well aware of and be attentive to just as they would for other medical conditions.

The effects of Lyme disease on people - particularly disseminated and late stage Lyme disease - are real and variable. Even if it becomes a post-infectious autoimmune condition, the damage done is real. The resulting symptoms need to be dealt with effectively. Medical societies and professionals need to step up to the plate and recognize them rather than write them off as imagined.


Related items of interest:


Dr. Phil Show In Three Parts - See the entire segment on Chronic Lyme disease.
Emory University Center for Ethics on an explanation that psychiatric illness is not imagined but a real condition - plus a mention that there is growing evidence of a biological basis for psychiatric disorders.
Economist on the pros and cons of toxoplasmosis.

* Stephanie, when interviewed on the show, stated she has had symptoms on and off for five years. According to her Twitter account and other online resources, she had a turn for the worse beginning in October 2011 and has been consistently ill since November 2011. So she hasn't yet been seriously symptomatic for the same period of time I was - let's hope she isn't.

Image Credit: 
Sick Girl, 1910 (Poland) - From commons.wikipedia.org under US-PD license.





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Friday, March 30, 2012

7 Did Isabel Diterich Have The Cure For Chronic Lyme Disease?

One researcher whose papers I've been reading recently is Isabel Diterich's. Several years ago she published two papers on Lyme disease which grabbed my attention because they not only revealed a hypothesis of immunosuppression caused by Borrelia burgdorferi spirochetes - but they also revealed a potential cure for chronic Lyme disease.

I say "potential" here with this caveat:

While the treatment did appear turn a man who was disabled into what sounds like the picture of health for at least eight years, he had to take filgrastim for almost two weeks. And filgrastim is an immune modulating drug which can have serious side effects in some people - there have even been a few fatalities.

However, most of the people who have suffered serious side effects from filgrastim were cancer and leukemia patients who already had serious health problems and were at greater risk for being affected by the drug. And most patients - including cancer patients - experience less dramatic effects of fatigue and joint pain from the use of filgrastim - something Lyme disease patients suffer with anyway.

Scary sounding as it is to take a drug which has the risk of serious or even fatal side effects, one has to consider that if better and safer immune modulating drugs could be developed - along with antibiotics - together they might be the cure for chronic Lyme disease.

To quote from Isabel Ditrech's 2003 thesis, "Immunomodulation and new therapeutic strategies in Lyme borreliosis":
"5.3.1 Case report

A 51 year old patient with a history of frequent exposures to tick bites presented with polyarthritis in the fingers and feet. Arthritic destruction of synovial clefts mainly in the metacarpophalangial and in the proximal interphalangial joints of fingers and feet could be demonstrated by X-ray. Low, but clearly positive, serum titers of Borrelia IgG by ELISA and immunoblot (p100 +++) and a negative IgM-ELISA (both MaxPettenkofer-Institute, Munich, Germany) corroborated diagnosis of late stage Borrelia infection.  
A standard two week i.v. treatment with 2 g/day Ceftriaxone (Rocephin,Hoffmann LaRoche, Grenzach-Whylen, Germany) led to transient improvement of symptoms, i.e. subjective decline of arthritis, that lasted for eight weeks. Then, the inflammatory symptoms returned and became progressively worse, indicating that the treatment had probably failed.  
We hypothesized that persistence of Borrelia might be due to a disabled immunocompetence of the patient. Therefore, we tested whether a complete eradication of the pathogen could be achieved by combining immunosupportive treatment with antibiosis. The experimental treatment regimen, applied with the informed consent of the patient, was as follows: First week 2 g Ceftriaxone (Rocephin ) i.v. daily, second week 480 µg s.c. Filgrastim (Neupogen, Amgen, Thousand Oaks, USA) every second day, and third week 2 g Ceftriaxone daily plus 300 µg Filgrastim every second day (Figure 5.1). Neutrophil counts were determined by a Coulter STKS counter (Coulter, Krefeld, Germany)"
So this lays out the background of this individual case report on one patient. What were the results? More quoted from the above thesis:
"5.4.1 Patient case report

The combination therapy of Ceftriaxone plus Filgrastim was well tolerated. Only after the first injection of Filgrastim the patient reported acute but moderate pain in the previously affected joints i.e. the shoulder, fingers and knees. 
Circulating neutrophil counts increased from 1400 to 17000 cells/µl within 24 h after the first Filgrastim injection. Monocyte numbers increased about two-fold, while there was little effect on lymphocytes (Figure 5.2a). The plateau of neutrophil counts at about 17000 cells/µl blood was maintained until one day after the end of treatment.  
The subjective symptoms disappeared during the following six weeks after the treatment. The patient reported that he was able to resume previously abandoned sporting activities including mountain climbing and downhill skiing. Moreover, fine mechanical skills needed for piano playing were restored. 
After three months, the Borrelia IgG titer was negative. The intensity of the immunoblot at this time point was significantly reduced (from +++ to +) and two years later it was negative. Eight years after treatment the patient is still free of arthritic symptoms."
Source:
http://kops.ub.uni-konstanz.de/bitstream/handle/urn:nbn:de:bsz:352-opus-9814/Diss_formated_ENDVERSION.pdf

So it seems like at least for this patient, this method of treatment changed their life so that they could return to all the things they used to do that they loved. I would have liked to know more about this patient and how he is doing today, given it has been years since this study was completed.

And I'd like to know if a similar treatment plan would work for me and everyone else suffering with chronic Lyme disease. To take ceftriaxone and filgrastim for a couple weeks - or something similar, but with fewer side effects - only to be done with this nightmare and get on with my life would be fantastic.

It would mean no more attempts at long term antibiotic treatment and experimentation with alternative medicine. I would just get treatment for three weeks and be done with it... Sounds like a plan to me.

Reflecting on this, over the years there have been anecdotes - stories I've heard passed around Lyme disease support groups - about the occasional chronic Lyme disease patient who went on to discover they had cancer, went through chemotherapy and other supportive treatment for their cancer - only end treatment not only going into remission from cancer  - but saying that they think their chronic Lyme disease is cured, too.

These stories have been around for a while, but I've never personally known anyone who went through this process. It would be great to get a confirmation from their doctors and families that after chemotherapy and supportive treatments, they had a notable and lasting improvement and feel like their old selves again. What if a drug like filgrastim played a role in their recovery?

This isn't the only example of a chronic condition where the cause has been unknown and the symptoms can be debilitating and lead to years of loss of productivity and physical pain... let's consider chronic fatigue syndrome, also known as CFS/ME or CFSIDS.

A study completed last year in Norway showed that rituximab had a profoundly positive effect on people with CFS/ME. In this study, a few people seemed to go into complete remission from their CFS and returned to work and led normal lives. It didn't work for everyone - 40% of study participants did not experience improvement from the drug. It's unknown why. But that it worked so well for the rest of treated patients deserves a closer look because it begins to reveal the mechanisms behind what causes CFS/ME.

While there has been speculation that chronic fatigue syndrome and chronic Lyme disease (CLD) are the same condition, a recent study on the different proteins found in the cerebrospinal fluid (CSF) of both CFS and CLD patients has challenged this notion. At least in terms of objective evidence, the proteins in the CSF of both groups are different. However, what if part of the underlying process behind what causes these conditions is the same?

Quoting the above well-written article from the Phoenix Rising ME web site, let's look at the mechanism behind rituximab and what it does in people with CFS/ME:
"Rituximab is believed to deplete B-cells in two ways; by recruiting other members of the immune system to attack them and by locking on a receptor on the B-cell that tells the cell to kill itself. B-cells are an integral part of the immune response. Until they are activated, B-cells quietly troll the blood, collecting and digesting molecules called antigens that appear to be suspicious. Once they are digested they place bits of them on MHC molecules for T-cells to inspect. If the T-cells decide those molecules came from a pathogen, they turn around and turn the B-cells on – transforming them into antibody producing machines (‘plasma cells’) that can generate from 100s to thousands of antibodies per second.

These antibodies or immunoglobulins are specifically manufactured to attach to a pathogen and physically stop it from locking onto our cells. The antibodies also alert macrophages to come gobble up the pathogen and they turn on other parts of the immune system. B-cells are key players in the immune response but if they go too far; if they get too zealous, they can mistakenly attack our own cells and overactive B-cell activity has been implicated in many auto-immune disorders."
If this sounds familiar to you, then you might have been reading about Viral Genetics' targeted peptide therapy, VGV-L, for treating chronic Lyme disease.

Viral Genetics' patent states the following about treating chronic Lyme disease:
"[0116] It is believed according to the invention that Borrelia burgdorferi also produces a Toll ligand for TLR2. Replacement of the CLIP on the surface of the B cell by treatment with a thymus derived peptide with high affinity for the MHC fingerprint of a particular individual, would result in activation of the important Tregs that can in turn cause reduction in antigen-non-specific B cells. Thus treatment with thymus derived peptides could reactivate specific Tregs and dampen the pathological inflammation that is required for the chronic inflammatory condition characteristic of Lyme Disease. With the appropriate MHC analysis of the subject, a specific thymus derived peptide can be synthesized to treat that subject. Thus individuals with all different types of MHC fingerprints could effectively be treated for Lyme disease."
An easier-to-understand explanation can be found elsewhere - this research report revealed how VGV-L is used to treat HIV. In this instance, just substitute "chronic Lyme Disease" for "HIV" and you can get a picture of what VGV-L does:
"The conventional approach to HIV vaccines, for example, is to develop therapeutic vaccines to stimulate immune system response. The problem with the conventional approach is that the infected cells are camouflaged and not visible to the body’s immune system. The body’s powerful T-cells are unable to seek out and destroy the infected camouflaged cells because they cannot recognize that the cell is infected.

To understand the issue, think of the Klingon space ship on Star Trek that has its cloaking device activated. The U.S.S. Enterprise has no way of knowing where the enemy is in space. The only hope it has in winning the battle is for the Klingon vessel to be de-cloaked and, once revealed, use their ammunition to destroy it. What’s worse in the case of HIV is that while the infected cell is cloaked, it is also effectively setting off an alarm that triggers the immune system to create inflammation. Why is this important? It turns out that this inflammation is critical for allowing the HIV virus to spread to even more cells.

Many other viruses and bacteria also trigger inflammation but, unlike HIV, the inflammation does not necessarily allow or facilitate the spread of the virus or bacteria itself. However, in these cases, the inflammation itself is harmful because it creates a hostile and inflamed environment that provides the necessary components for a potential autoimmune reaction that can cause the immune system to attack and damage one’s own body. Viral believes that diseases such as Lyme Disease, Multiple Sclerosis and others involve this inflammatory mechanism.

To use the Star Trek metaphor, what Dr. Newell Rogers has developed with TPT is a de-cloaking device for the body’s immune system to use in its pursuit of invaders. Through the development and use of computational biology programs and databases, Dr. Newell Rogers and her team have created a way to remove the camouflage that is cloaking the infected cells, flagging them with custom peptides that allow the body’s immune system to seek out and destroy them.

The key discovery of the TPT platform is that a self-peptide (in other words, one that is naturally produced and a healthy part of one’s normally functioning immune system) called ―CLIP2 that was until now thought only to exist primarily inside certain immune system cells, is sometimes displayed on the outside of cells, thus leading to harmful inflammation. Dr. Newell Rogers discovered that the products of some pathogen invaders such as viruses and bacteria, when picked up on the surface of certain immune system cells, sometimes incorrectly cause those cells to display CLIP externally (i.e. ―ectopically).

Normally, when an invader strikes, this process may promote needed inflammation early in infection, but it is quickly controlled when a more specific, immune response takes over, allowing a highly-targeted immune response to be marshaled against the pathogen. However, when CLIP is improperly displayed, displayed for too long or displayed chronically, the immune system is marshaled to promote a broad and unspecified inflammation without the specific targeting, leaving open the possibility that this inflammation actually turns against one’s own cells. Replacing CLIP is the focus of Viral’s Targeted Peptides because it turns off the harmful alarm."
Read more from the source - including about individual MHC genetic profiles here: http://www.viralgenetics.com/investors/press-releases/Research_2.0_Report_Feb1_2011.pdf

They're using Star Trek metaphors to describe this... I think that's pretty geeky. Awesome.

So, it seems that whether there is current infection or not, VGV-L may be one way to effectively treat chronic Lyme disease and lower inflammation due to runaway immune dysregulation. And if infection is currently present, then it looks like VGV-L will trigger T cells that recognize the infection and summon functional B-cells to fight it.

Now, getting back to Isabel... Remember Isabel, the researcher who used filgrastim and ceftriaxone to treat a patient with chronic Lyme disease about a decade ago? Yes, that Isabel.

Well, she wrote another paper, along with Rauter, Kirshning, and Hartung: "Borrelia burgdorferi-Induced Tolerance as a Model of Persistence via Immunosuppression"

The abstract states:
"If left untreated, infection with Borrelia burgdorferi sensu lato may lead to chronic Lyme borreliosis. It is still unknown how this pathogen manages to persist in the host in the presence of competent immune cells. It was recently reported that Borrelia suppresses the host's immune response, thus perhaps preventing the elimination of the pathogen (I. Diterich, L. Härter, D. Hassler, A. Wendel, and T. Hartung, Infect. Immun. 69:687-694, 2001). Here, we further characterize Borrelia-induced immunomodulation in order to develop a model of this anergy. 
We observed that the different Borrelia preparations that we tested, i.e., live, heat-inactivated, and sonicated Borrelia, could desensitize human blood monocytes, as shown by attenuated cytokine release upon restimulation with any of the different preparations. Next, we investigated whether these Borrelia-specific stimuli render monocytes tolerant, i.e. hyporesponsive, towards another Toll-like receptor 2 (TLR2) agonist, such as lipoteichoic acid from gram-positive bacteria, or towards the TLR4 agonist lipopolysaccharide. Cross-tolerance towards all tested stimuli was induced. Furthermore, using primary bone marrow cells from TLR2-deficient mice and from mice with a nonfunctional TLR4 (strain C3H/HeJ), we demonstrated that the TLR2 was required for tolerance induction by Borrelia, and using neutralizing antibodies, we identified interleukin-10 as the key mediator involved."
Source: http://iai.asm.org/content/71/7/3979.full

Where have I heard something like this before? Oh, Dr. Karen Newell Rogers - that's right - she discussed this at a recent Lyme disease research conference:

"[...]Some researchers would argue that chronic inflammation requires the continuous presence of bacteria, whereas others would suggest that continuous presence of bacteria does not always result in inflammation and that exacerbations of chronic symptoms could result from infection with a different organism--or that chronic symptoms could re-cur from unrelated pro-inflammatory events. Potentially reconciling these seemingly conflicting perspectives on the mechanism of Lyme disease may be the effect of Borrelia burgdoreri’s bacterial by-products on Toll Like Receptors, (TLR)-mediated immune activation. 

TLR appear to be the “gate-keepers” of an inflammatory response. Bacteria, including Borrelia, produce products that, by binding to TLRs on the cell surface, promote leukocyte activation, cytokine production, and acute inflammation. In some genetic backgrounds of mice, acute inflammation is sufficient to fight off infection and resolve disease. In other mouse strains, the pathogens, or in this case the bacteria, get past TLR-induced inflammation and remain symptomatically undetectable in cells and tissues (Barthold, etc); Barthold et al. have found that no matter how severe or mild the disease in any of the genetically inbred strains of mice, there was no more inflammatory disease when the bacteria were eliminated."
And where else have I heard about IL-10 production before? Oh, right - Rituximab, and research on gender differences in antibody response to Borrelia burgdorferi...

From the previously mentioned Phoenix Rising ME article:
"While Rituximab is busy destroying B-cells there is also evidence that it may actually be turning on NK cells – which, of course, habitually underperform in CFS. Rituximab also appears to increase production of IL-10 – a key anti-inflammatory cytokine that may be a protective agent in ME/CFS – and reduces levels of the powerful pro-inflammatory cytokine tumor necrosis factor. A review article suggested that Rituximab was able restore Th1/Th2 balance in the immune system. These results suggest Rituximab could be working as an immunodulator helping to re-balance the immune response by turning down the over-activated parts of it and bumping up the under-active ones."
All this ties together quite nicely, it seems, with other research I have listed here - forming a master hypothesis with different pieces. Does it hold up to scrutiny? Tell me - I'd love to hear your ideas.

But here is the master hypothesis, in its infancy:

1) Host genetics play a role in the ability of mice (and possibly people!) in clearing Borrelia burgdorferi infections. See:

http://campother.blogspot.com/2011/08/immune-infection-hla-dr-alleles.html

The host's genetic background in developing chronic infection is, however, open to debate - and may not play as big a role in disease as Borrelia burgdorferi s.l.'s genetic diversity/VlsE recombination on different plasmids:

http://campother.blogspot.com/2011/08/do-different-genetic-haplotypes-matter.html
http://campother.blogspot.com/2011/08/more-on-genetic-haplotypes-and-lyme.html

2) The genetics of Borrelia burgdorferi strains play a role in how quickly they disseminate into host tissues and also how well they can generate inflammation - which leads to overstimulation of the immune system in production of poor quality plasma b-cells, but also, ironically, immune suppression because of the mechanisms Isabel Diterich and Karen Newell Rogers describe. Refer, also, to Tunev and Barthold et al's research, "Lymphoadenopathy during Lyme Borreliosis Is Caused by Spirochete Migration-Induced Specific B Cell Activation":

http://campother.blogspot.com/2011/06/paper-borrelia-burgdorferi-rst1-ospc.html
http://spirochetesunwound.blogspot.com/2011/07/does-borrelia-burgdorferi-cause.html
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1002066
http://spirochetesunwound.blogspot.com/2010/07/antigen-presentation-in-bloodstream-how.html (refer to other research on relationship between b-cells/plasma cells and T cells)

It could also be that not having enough iNKT cells is an issue:
http://www.pnas.org/content/105/50/19863.full.pdf

2a) The changing pattern of antigenic variation during this time may also be why patients produce an undulating immune response in measured antibodies which echo a more drawn-out response similar to relapsing fever:

http://campother.blogspot.com/2012/02/paper-course-of-antibody-response-in.html
http://campother.blogspot.com/2011/08/antibodies-linked-to-long-term-lyme.html (read comments, too)
http://www.ncbi.nlm.nih.gov/pubmed/9108482
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2772371/
http://www.ncbi.nlm.nih.gov/pubmed/11544329
http://campother.blogspot.com/2011/07/lyme-disease-western-blots-and-antigen.html

It may not be that the tests are lousy for measuring antibodies which are present to Borrelia burgdorferi. It may be that the antibodies are not present because they are tied up in immune complexes.

2b) There is also the possibility that Borrelia burgdorferi is occasionally intracellular in nature, though there is not enough in vivo evidence to support this. If so, it would also explain why an undulatory immune response might be present:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3067508/?tool=pubmed
http://campother.blogspot.com/2011/07/fibroblasts-and-lyme-disease-sample.html

Whether or not items #2a and #2b are relevant here remains to be seen - the main point is that Borrelia burgdorferi can lead to both overstimulation of the immune system as well as immune suppression.

Based on this, I surmise that may not be that blood tests are so lousy at detecting antibodies produced by the presence Borrelia burgdorferi. It may be that there is no reliable way to detect the presence of infection by correlating them with the presence of antibody responses (seronegative Lyme disease).

3) What gender you are and your hormone levels and metabolism may play a role in persisting symptoms and prolonged infection as well, so there is ALSO a metabolic cause behind chronic Lyme disease. How well the immune system can respond to initial infection to begin with seems to play a role in developing chronic Lyme disease, as even 10% of acute cases of Lyme disease result in treatment failure.

http://campother.blogspot.com/2012/03/lyme-disease-presents-differently-in.html
http://campother.blogspot.com/2012/01/two-new-hypotheses-for-chronic-lyme.html (read comments, too)
http://www.ncbi.nlm.nih.gov/pubmed/17438273 (this may provide the scientific link for the anecdotes that people who develop chronic Lyme disease generally were under more stress when they contracted the disease)

4) If there are persister cells, this is an additional consideration - throwing more antibiotics at a pathogen which is antibiotic tolerant when it is a persister cell will, at most, keep the infection from getting worse but it won't eliminate it.

http://campother.blogspot.com/2012/01/paper-persistence-of-borrelia.html
http://campother.blogspot.com/2012/02/blog-log-spirochetes-unwound-on.html

See also:
The research of Kim Lewis on persister cells: www.bu.edu/abl/files/killing_persisters.pdf
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145328/

And it may be that persister cells are more likely to be on the scene earlier, depending on how appropriate a given antibiotic is for treating specific genospecies - refer to item #2 above, but also:

http://campother.blogspot.com/2011/05/abstract-evaluation-of-in-vitro.html

5) Because the host has a sub-optimal immune system, even with long term antibiotics, a subset of the population will have trouble clearing the remaining spirochetes after antibiotics are stopped. Additional antibiotics plus a treatment which eliminates low quality plasma b-cells and promotes the activity of Treg cells which recognize current infection could overturn the dysregulated immune system.

What does this boil down to?

Easy: The argument of "is it a chronic infection or is it an immune disorder, possibly autoimmune" is a false dichotomy and too simplistic.

The circumstances which give rise to chronic Lyme disease are more complex than that, and if people want to solve the chronic Lyme problem, they have to roll up their sleeves and look at more puzzle pieces and how they fit together.

Image credit: 
Original image by Muns on Wikimedia Commons; derived image above by Schlurcher.


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Tuesday, November 22, 2011

0 Article: The Mouse Trap: How One Rodent Rules The Lab

Slate recently posted a three part series on the use of mice in biomedical research and how that use has helped as well as hindered drug development and scientific understanding of human illness.

This three part series kicks off with "The Mouse Trap: the dangers of using one lab animal to study every disease", which examines the rise in the use of the murine (mouse) model  to test new pharmaceuticals and get a better understanding of human processes in illness. We also learn that this model - useful as it has been - has its drawbacks.

 Mark Mattson, neuroscientist, finds that murine studies may not accurately represent what happens between the study and control group when the control group is often overfed, sedentary, and develops cancer, renal problems, and diabetes - unlike a wild mouse living in its normal habitat. It was later discovered that medication which worked in chubby rodents did not go on to work in rodents with a normal weight and activity level.

Furthermore, in clinical trials on humans later on, the difference between plump mice and a diverse group of humans was too great. A drug which worked in the rodents did not work in humans at all.

Cheap, efficient, and mass produced, these mice are raised in germ-free barrier rooms and sometimes pumped with antibiotics. The ease in which they can be raised, bred, and genetically modified to single out specific processes similar to those in the human body to study has made mice very popular for researchers. While they can closely model many processes in the human body, are they a close enough match for modeling and testing everything?

Mattson argues they are not, and that science needs to wake up and take a closer look at how heavily mice have been used to make decisions that affect human medicine. He's not the only one, either - Clif Barry, the nation's leading expert on tuberculosis, thinks the murine model has shortcomings too. This is no clearer than in work in his own field: The latent form of TB that humans get is not one which can be found in mice. Mice do not experience a latent stage of TB - they only get progressively weaker, age, and die.

This particular passage from the article gave me a moment to pause and reflect:
"[...] for some patients a latent case of tuberculosis can suddenly become active. The granulomas rupture and propagate, spilling thousands of organisms into the lungs, where they can be aerosolized, coughed up, and passed on to a new host. Left untreated, the infection migrates into the bloodstream and other organs; widespread inflammation leads to burst arteries or a ruptured esophagus; and in about half of all cases, the patient dies.

The layered granuloma is the defining feature of human tuberculosis: The place where the host fights the infection (successfully or not), and the necessary site of action for any drug. To cure the disease, a treatment must be able to penetrate each ball of cells, whatever its type or composition; every last bacterium must be destroyed. "It's the structure of those granulomas that makes it so difficult to treat TB," says Barry. And they simply don't exist in mice.

If you infect a mouse with TB—if you spritz a puff of infected air into its nostrils through a trumpet, as so many labs do around the world—the animal's lungs quickly fill up with bacteria and immune cells, like a nasty case of pneumonia. There are no discrete balls of tissue, no well-defined granulomas sheathed in fibrin, no array of structures that harbor the bugs at various stages of development. The mice have no special, latent form of TB, either, and no way to pass on the disease. They simply die, after a year or two, of a slow and progressive decline.

That's why we've made so little progress using mice to generate new drugs and treatments, Barry tells me."
The article continues to outline the history behind why mice have become the dominant research model to use to determine whether or not a drug or treatment plan will be tried in clinical trials on people, and also discusses the setbacks generated by this decision. In the end, the verdict is that using mice has distinct limitations and a number of studies may be invalidated and useless because of it.

It does get me to wondering, of course, as to how useful the murine model is for studying Borrelia burgdorferi. Perhaps in some ways it is useful, but in others it is less so: Dr. Stephen Barthold has said mice are a poor model for neuroborreliosis.

And this does raise the question of which details are important in a study that the layperson will miss when reading it. The average person will read about the study design, and perhaps some discussion and the conclusion - but will one question the decision to use one research animal model over another? What about primers? What about media? What about any number of small details that once changed could result in a different outcome?

Read the full Slate article, and continue with the next two articles in the series. It is a fascinating look into the world of biomedical research, tradition, and profit.

Reference: http://www.slate.com/articles/health_and_science/the_mouse_trap/2011/11/lab_mice_are_they_limiting_our_understanding_of_human_disease_.html


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Tuesday, November 8, 2011

0 Two Notable Antibiotic Articles - Long-term Effects & Alternatives

H. pylori: Friend or foe?
Answer: It depends...
I know some of you reading along may have already seen this, but I think it bears mentioning again and also bears mentioning for those who may not have seen it: The New York Times recently published an article on the long-term effects of antibiotic usage, "In Some Cases, Even Bad Bacteria May Be Good".

After reading the above link, I found it fascinating and disturbing that antibiotics not only could contribute to obesity - the hypothesis originally being test driven by the writer - but that antibiotic use could also lead to allergies, inflammatory bowel disease, asthma, and gastroesophageal reflux. These are conditions which are not only common in Lyme disease patients, but in the general population as well.

Among the astonishing findings in this article:
  • Eradicating H. pylori infections entirely leads to the inability of ghrelin (a hunger hormone secreted in the stomach) to decrease in the stomach, thus leaving the brain to think it's always time to eat more. Therefore, lack of infection = eating more = weight gain.
  • Researchers found that the ratios of various bacteria in the guts of obese mice and obese humans were significantly different from those of lean controls, suggesting that altering the stomach’s microbial balance with antibiotics might put patients at risk for gaining weight. H. pylori is not the only culprit for change.
  • Less H. pylori in someone's system is associated with a greater risk of not only asthma but gastric reflux disease as well.
  • The human body contains a very complex bacterial ecosystem which we don't know anywhere near as much about as we should. Knowing about it is important in understanding the cause for disease and how to prevent it.
  • It's not just antibiotics that are changing the human microbiota - many aspects of modern life, including diet, smaller families, more hygienic practices and improved public sanitation, are affecting our bacterial communities.
The research cited contains sobering news and adds to the realization that as much as antibiotics have brought deadly infections under control and saved lives, they can have negative side effects and possibly more longer term consequences than at first realized.

All this said, I have been an advocate of antibiotic usage to treat Lyme disease - especially in its early stage and with a clear case of neuroborreliosis - because antibiotics have been tested and used in clinical trials for many years for their effectiveness. It's  important in the case of neuroborreliosis to ensure that treatment can pass the blood-brain barrier, and so far antibiotics have been tested which are demonstrated to have this property.

So I still stand by the use of antibiotics for their effectiveness and documented record for helping patients everywhere. However,  I am aware that in the future, antibiotics may not work as well as they once did due to antibiotic resistance, and this knowledge of longer term effects concerns me as well. Alternatives will need to be found that are safe and effective.

What sort of treatment could be available other than antimicrobial herbs?

The answer may be as close as your local wallaby.

Okay, well, for most people reading this, wallabies are hardly local to them - unless you are one of my Australian readers or you have a decent zoo nearby.

Last month, Byte Size Biology blog published an entry on the innate immune system and research on cathelicidins, specifically those peptides found within marsupials - including wallabies - which can fight off infection.

A baby kangaroo (joey) or wallaby is born in its fetal stage and must travel across its mother's abdomen and into a pouch to complete development. This can expose the fragile fetus to all sorts of germs, so what protects it? While the joey has adaptive immunity which is quite undeveloped, it can produce some killer all-purpose peptides he can use against microbes.

The same class of peptides are produced in Kanga’s milk. (Think of the idea as being similar to colostrum in cows, perhaps?) Collectively they are known as cathelicidins. Only about 30 amino acids long, these highly charged molecules kill both gram-positive and gram-negative bacteria.

Preliminary studies were conducted on the use of cathelicidins as antibiotics. The author of Byte Size Biology wrote:
"They used cathelicidins from wallaby and platypus to kill human pathogens: P. aeruginosa, K. pneumoniae and A. baumanii, including antibiotic resistant strains. Cathelicidins were much more effective than, well, antibiotics against those bacteria. Also, cathelicidins did not kill human red blood cells, which makes them a potential drug. Of course, immune reaction against cathelicidins as a foreign still needs to be checked, among many, many other things, but the whole idea of looking at marsupials is that, as mammals, they may be able to supply us with clues on how to synthesize a cathelicidin to be used as a drug in humans."
More research is needed, obviously, but this may be one option to antibiotics sitting in your medicine cabinet of the future.

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Thursday, October 20, 2011

0 Where Have All The Sane Lyme Patients Gone?

Here is an exchange I've seen elsewhere on the internet, names removed to place more focus on the content:

Do you think that morgellons stuff is a joke? Or lida mattman saying that Lyme can be transmitted by doorknobs and pens? Or that every sample she's ever seen shows Lyme?

No, those who put forth these theories are not joking. And no, I do NOT believe these things. And YES, I think they are damaging.

there are minions ready to believe anything.

This is true --patients who remain ill and find themselves fighting mainstream treatment guidelines have become angry and confused, and almost anything sometimes seems possible to them. They lack the scientific/medical background to distinguish.

Sober? Maybe. Not when they insist that mcsweegan is poisioning their well water though. I've heard some crazy stuff.

This is an old story. Let's move on. The baton has passed.

More sober and savvy than most people who have ever posted here? Sure. But that is like saying that they see and hear better than Helen Keller.

Many times people work behind the scenes because of forums like sci.med, which have gotten issues so knotted and confused.

I know some people with Lyme who aren't extremists. But they're few and far between.

Define extremist: In some circles, simply believing the cure didn't take after 28 days doxy is considered extreme. I find that if I talk to people logically and rationally they can respond in kind. Most people I have met in Lyme are turned off by the outrageous antics of the most notorious protagonists here, and I will not name the names. I don't know who you have met --but those I speak to, while sometimes empathetic, are NOT marching in line with a RICO lawsuit.

I've seen more than one "llmd" and waited in their waiting rooms with other lyme patients and heard them start talking or started talking with them. They're "informed" but don't seem to distinguish between what is good information and what isn't.

They are very confused by the situation --but the confusion starts with what medicine has handed down to them, not with the patients. If you create an artifactual disease that people don't have, then the patients who don't fit your model might be accused of factitious illness. It's a very frustrating situation for patients. The psychopathology starts with medicine, and patients are caught up and then labelled pathological, themselves. It is one of those Freudian boxes --the patients find there is no way out.

I don't see a lot of rationality anywhere.

It's hard to be rational in the face of an irrational situation that predated your involvement.

I don't think that two wrongs make a right and that rigid academic experts views are "balanced" by the views here.

Of course I do not believe this --I am simply saying that extremism begets extremism. I hold to my view that the dysfunction in Lyme was kicked off by biomedicine and not by patients.

It is just as easy to conclude that both are wrong and that maybe the "truth" is somewhere in between. Or nowhere in between but somewhere else entirely.

You must resolve dysfunction before you attempt to learn the truth.

I think you're glossing over things. Let's say you reject what the  academics say. Why does that mean that you have to buy into what Lida Mattman says?

I don't buy into what Mattman says. And nor do I reject academic research --some of what the academics say is right-on. But some of them have misused their craft and trampled the scientific method (perhaps unwittingly) in the process creating an unduly restrictive disease definition, discarding or twisting data, and spawning an untenable, dysfunctional situation out in the field. Most patients who appear dysfunctional once they get to Lyme were perfectly functional before --it is the scene and the situation --the disturbing dissonance between patient experience and medical paradigm-- that is at fault.

Rejecting the false negatives on elisa or western blot doesn't mean accepting a specific Lyme speciality lab's test results does it?

we don't need to keep debating this --of course not.

Have Lyme patients made things better?

Sadly things have not gotten better, but worse, IMO.

So you didn't answer the question. Where have all the sane Lyme patients gone?  Where is the forum, in real life or on the internet where I can find them? Where do they dominate? Where is rationality revered over reactionary radicalism?

I have met many MANY sane Lyme disease patients. I am sorry you have not. They are everywhere.

Lyme patients are fully to blame for how they've responded to the medical establishment.

Lyme patients are between a rock and a hard place --they have been dismantled, dismissed, and made fun of; they have been misdiagnosed for so long they develop chronic illness when they could have been totally cured. Lyme patients are angry. But they have not often strategized well in the past, I'll grant you that.

It's been a very bad confluence of situations and personalities all around, I'm afraid. It is, in short, a disaster: But if you don't look to what has transpired in medicine and science to stanch out the dysfunction, you will be spinning your wheels to the end of time. Should Lyme patients do a better job of achieving this? Yes of course.



And another comment from a Chronic Lyme Disease patient seen elsewhere, from someone who reminds me of LymeEngima (but was not identified as such):

"I have Chronic Lyme and I hated the movie “Under Our Skin”.  All it did was try and instill panic in people who are already sick and vulnerable to making desperate choices.  [...]
The IDSA Guidelines scare me. The doctors who treat Lyme scare me. The treatments scare me and the fear and anger around the whole subject scares me. Nothing about Lyme resembles even handed scientific principles and more closely resemble hysteria."

Comments such as this are rare to come by online. Few Lyme disease patients have said anything negative about UOS or admitted that everything about Lyme disease scares them.



These comments are a prelude to my own post about why and how dealing with Lyme disease drives me crazy, so I put them here for review and discussion.

Any thoughts from those of you reading along?

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Tuesday, October 18, 2011

0 Abstract: European neuroborreliosis: neuropsychological findings 30 months post-treatment.

European neuroborreliosis: neuropsychological findings 30 months post-treatment.
Eikeland, R., Ljøstad, U, Mygland, Å., Herlofson, K., Løhaugen, G. C.
European Journal of Neurology.1468-1331.
http://dx.doi.org/10.1111/j.1468-1331.2011.03563.x

Background:  The aim of this study was to compare neuropsychological (NP) functioning in patients with Lyme neuroborreliosis (LNB) 30 months after treatment to matched controls.

Methods:  We tested 50 patients with LNB and 50 controls with the trail-making test (TMT), Stroop test, digit symbol test, and California Verbal Learning test (CVLT). A global NP sumscore was calculated to express the number of low scores on 23 NP subtasks.

Results:  Mean scores were lower amongst LNB-treated patients than amongst controls on tasks assessing attention/executive functions: (Stroop test 4: 77.6 vs. 67.0, P = 0.015), response/processing speed (TMT 5: 23.4 vs. 19.2, P = 0.004), visual memory (digit symbol recall: 6.6 vs. 7.2, P = 0.038), and verbal memory (CVLT list B: 4.68 vs. 5.50, P = 0.003). The proportion of patients and controls with NP sumscores within one SD from the mean in the control group (defined as normal) and between one and two SD (defined as deficit) were similar, but more LNB-treated patients than controls had a sumscore more than two SD from the mean (defined as impairment) (8 vs. 1, P = 0.014). Conclusions: As a group, LNB-treated patients scored lower on four NP subtasks assessing processing speed, visual and verbal memory, and executive/attention functions, as compared to matched controls. The distribution of NP dysfunctions indicates that most LNB-treated patients perform comparable to controls, whilst a small subgroup have a debilitating long-term course with cognitive problems.



Questions to consider:


1) If one did a protein study of the CSF between those in the small subgroup having a debilitating long-term course with cognitive problems and the rest of the neuroborreliosis group, would differences be found between samples?

2) What was the difference in scoring in this most affected subgroup compared to the other patients who had neuroborreliosis?

3) Is there research which uses the same methods and compares pre- and post-treatment neuroborreliosis patients?


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Wednesday, September 28, 2011

0 Blog Log: Spirochetes Unwound on Flawed Study of Topical Antibiotics

Remember that article on topical azithromycin I posted earlier this month?

Our favorite spirochete blogger has some criticism about the research on which it was based here:

http://spirochetesunwound.blogspot.com/2011/09/flawed-study-claiming-prevention-of.html

A flawed study claiming prevention of Lyme spirochete infection with topical antibiotics

Two recent papers tested the effectiveness of topical antibiotics in preventing Borrelia burgdorferi infection in mice following a tick bite. Infection by the Lyme disease spirochete was successfully halted in the Knauer et al. study from Germany1 but not in the Wormser et al. study conducted in New York.2 However a flaw in the Knauer study may have unfairly tipped the outcome in the antbiotic's favor. (I'll save the Wormser study for another post.)

READ MORE HERE >>>


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Wednesday, September 21, 2011

0 An accident leads Yale scientists to tick-borne disease in Russia

The Connecticut Mirror has an article on the backstory behind discovering that Borrelia miyamotoi leads to infection in people:

An accident leads Yale scientists to tick-borne disease in Russia
http://www.ctmirror.org/story/13955/lyme-new-tick-borne-disease-yale

You've got to love this excerpt:
Fish's lab was studying Lyme disease transmission using ticks and mice, exposing ticks to mice that had been infected, and to others that had not. But the ticks exposed to uninfected mice appeared to be infected.

"I gave everybody in the lab hell for wasting a lot of time and resources and stuff, because they screwed up the experiment," said Fish, a professor of epidemiology at the Yale School of Public Health. "And they felt really bad and they couldn't understand how that happened."

In fact, the ticks had a different bacterial organism, not the one that causes Lyme, but a distant relation called Borrelia miyamotoi. It had been identified six years earlier in Japan, but no one knew if it caused illness in humans. Fish spent the better part of a decade trying to get funding to study it, with little success.

I guess I have these questions about this:

1) Has anything similar happened before in other experiments and we don't even know about it - this situation of having uninfected mice be infected by a different organism that is disease-causing?

2) Why wasn't there enough funding to study this? Who decides which projects get funded?

3) I noticed that Borrelia research at the NIH got a lot more funding in the past two years... What were the goals of the bulk of those projects?

I can probably find out the answer to #3 with some digging. The first two questions? Not as easy to answer.


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Tuesday, September 20, 2011

0 How To Avoid Sample Contamination

A quick and dirty primer for those who want to ensure that their samples do not get cross-contaminated with DNA from other bacteria, viruses, etc.:
  1. Use aerosol barrier pipette tips.
  2. UV-irradiate all workstations used for the setup of master mix preps and PCRs.
  3. Treat all surfaces and tube racks with a 10% bleach solution.
  4. Use frequent and careful glove changes.
  5. Perform DNA extraction, PCR setup, and PCR product analysis in different rooms.
  6. Use clean systems.
  7. Use a negative control such as UV-treated, deionized water.
  8. Do not do bacterial work, etc. during any human DNA extraction.
Follow these simple tips, and then when others look at your research and claim that Borrelia burgdorferi could only be found where it was due to  sample contamination, point out that a number of steps were taken to prevent it.

At what point when an experiment is repeatedly reproducible does one stop saying the end result was due to sample contamination and begin saying the end result was genuine?

What other steps can you take to prevent and eliminate sample contamination?

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Saturday, July 30, 2011

0 Admin: PSA To All Camp Other Google Account Users And Readers

A message from Camp Other to readers:

Keep your eyes on Google and how they treat your accounts - especially if you have and use a pseudonym online connected with Google+ accounts.

BEFORE:

http://googlepublicpolicy.blogspot.com/2011/02/freedom-to-be-who-you-want-to-be.html

"When it comes to Google services, we support three types of use: unidentified, pseudonymous and identified. And each mode has its own particular user benefits.

Unidentified. Sometimes you want to use the web without having your online activity tied to your identity, or even a pseudonym—for example, when you’re researching a medical condition or searching for that perfect gift for a special someone. When you’re not logged into your Google Account (or if you never signed up for one), that’s how you’ll be using our services. While we need to keep information like IP addresses and cookies to provide the service, we don’t link that information to an individual account when you are logged out.

Pseudonymous. Using a pseudonym has been one of the great benefits of the Internet, because it has enabled people to express themselves freely—they may be in physical danger, looking for help, or have a condition they don’t want people to know about. People in these circumstances may need a consistent identity, but one that is not linked to their offline self. You can use pseudonyms to upload videos in YouTube or post to Blogger.

Identified. There are many times you want to share information with people and have them know who you really are. Some products such as Google Checkout rely on this type of identity assurance and require that you identify yourself to use the service. There may be other times when it’s more desirable to be identified than not, for example if you want to be part of a community action project you may ask, “How do I know these other people I see online really are community members?”

Well, this all sounded like a reasonable division to me, and that's worked fine for me for ages.

AFTER:

But during the past month, Google apparently began shutting people's Google accounts down across the board without warning - because users were using pseudonyms.

I only learned about this within the past 24 hours (I guess I've been too buried in research about antigenic variation and serology to notice the news lately) and was disturbed to hear about what happened to GrrlScientist and her accounts.

Apparently a lot of people's accounts were suspended without prior notice, and outrage over this spread across the blogosphere. Search online for "privacy, pseudonyms, and google accounts" and you are likely to find more information on this action from more than one web site.

At any rate, looking at the stream of events unfolding, I've had to wonder if Camp Other blog would be next. If so, I'll be posting an announcement on Lymenet Europe letting people know where the site would be getting moved - somewhere without a policy that discriminates against anonymity - and pseudonyms in particular.

THE STORY TODAY:

But, it may be that my search for an ISP to host my blog would be premature, as I just came across an announcement from Bradley Horowitz on Google+ that came from a discussion between Robert Scoble of Rackspace and Vic Gundotra, Senior VP of Social at Google - the most important snippet posted below:

MYTH: Not abiding by the Google+ common name policy can lead to wholesale suspension of one’s entire Google account.

When an account is suspended for violating the Google+ common name standards, access to Gmail or other products that don’t require a Google+ profile are not removed. Please help get the word out: if your Google+ Profile is suspended for not using a common name, you won't be able to use Google services that require a Google+ Profile, but you'll still be able to use Gmail, Docs, Calendar, Blogger, and so on. (Of course there are other Google-wide policies (e.g. egregious spamming, illegal activity, etc) that do apply to all Google products, and violations of these policies could in fact lead to a Google-wide suspension.)

Camp Other doesn't use Google+ in the first place, so I am making the assumption based on the above that my blog will continue to operate on Blogger as it has been.

If something changes... well, you know where to find me. And if Lymenet Europe for some reason goes down, I'll post to CanLyme, and so on - to other Lyme disease related forums which have not unceremoniously banned me.

CO

PS: Just in case you wondered, I make a regular backup of all the site entries. Reformatting the content and moving to another web site host may not be a trivial matter, though, so I don't want to do it unless there's a very compelling reason.

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Monday, July 11, 2011

0 Blog Log: Retraction Watch

Readers might be interested in the blog, Retraction Watch (it's listed on my right sidebar, too, and not just in this entry).

Retraction Watch is a blog with two authors - namely Ivan Oransky, the executive editor for Reuters Health, and Adam Marcus, the managing editor for Anesthesiology News - who write about scientific papers which are fully or partially retracted from different journals.

Retraction - to those uninitiated into the ways of scientific publishing - means that the authors of the paper are either found to have faulty data and/or conclusions for their paper or report it themselves, and the paper is removed.

To give a more involved definition from Wikipedia:

"A retraction is a public statement, by the author of an earlier statement, that withdraws, cancels, refutes, diametrically reverses the original statement or ceases and desists from publishing the original statement. Retractions may or may not be accompanied by the author's further explanation as to how the original statement came to be made and/or what subsequent events, discoveries, or experiences led to the subsequent retraction. They are also in some cases accompanied by apologies for previous error and/or expressions of gratitude to persons who disclosed the error to the author."

So today's Retraction Watch entry, "So how often does medical consensus turn out to be wrong?", is of particular interest to those who question the utility and basis for medical and clinical treatment recommendations.

Here is an excerpt:
"In a quote that has become part of medical school orientations everywhere, David Sackett, often referred to as the “father of evidence-based medicine,” once famously said:

Half of what you’ll learn in medical school will be shown to be either dead wrong or out of date within five years of your graduation; the trouble is that nobody can tell you which half–so the most important thing to learn is how to learn on your own. 
Sackett, we are fairly sure, was making a wild estimate when he said ”half.” But a fascinating study out today in the Archives of Internal Medicine suggests that he may have been closer than any of us imagined."
With that, you know we're off to a good start...

Read more at Retraction Watch >>>

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Friday, June 3, 2011

1 I've Got You... Under My Skin

There you folks go.

Seriously, if you stopped for just one moment and responded to the naysayer's comments with evidence, then the conversation might be more productive...

Exchange online, identities removed and exact words modified because they aren't necessary to make the point - and besides, one was anonymous, anyway:

Party A: 

"I was not impressed by this movie. It is a rant against Big everything. There's no explanation of what is wrong with the guidelines. I'd like to see LLMDs explain what chronic Lyme disease is, explain which guidelines are in error and why, and then present research which contradicts research cited in the guidelines. I don't expect this will happen any time soon. I don't understand why everyone is so conspiracy theory about this and isn't looking at the problem logically.

Why would Big Pharma not want use of long term antibiotics since it's money making?

Further Comments from (assumed same) Party A:

"The guidelines have research citations. I have no issue with questioning them, it's how better ones are made. But any change must be based on research not anecdote. When someone can define what "persistent Lyme disease is" and use DB RCS with the right methodology and show longer term antibiotic therapy is good then the guidelines will change."

(Remainder of comment scrapped for repeating much of previous comment made above.)

Party B response to Party A:

"Clearly, you are clueless - even after watching the film. If you ever get Lyme disease (chances are high, considering it's an epidemic), you won't like these guidelines so much."

Party C response to Party A:

"You sound just like these two guidelines supporters and authors of guidelines. If you want to know more about it then read. Or better yet get bit by a tick and get sick and see what life is like for a Lyme disease patient."

(Remainder of comment thread removed for brevity.)

Hi, I'm sorry you are suffering. This disease sucks, and I hate it, too.

Unfortunately, this isn't making a strong case in support of the issues we're facing here and providing a well reasoned counterpoint to Party A - whoever they are - is important. (And they could be anyone who is skeptical and wants to know the answers to their questions.)

If you can convince them of the problems patients are facing, then you can convince just about anyone.

I suggest that you read the following links:
http://campother.blogspot.com/2011/05/chart-ways-to-discuss-your-position-in.html
http://campother.blogspot.com/2011/05/repost-lyme-disease-rant-wall-of.html

You can win in an argument - or at least present information which will get others to think, including those observing your exchange who do not comment at all.

Remember that for every comment you write and receive, there are hundreds of people who say nothing and your comment and your post has an effect on them.

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The Camp Other Song Of The Month


Why is this posted? Just for fun!

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