New device stores electricity on silicon chips.


Solar cells that produce electricity 24/7, not just when the sun is shining. Mobile phones with built-in power cells that recharge in seconds and work for weeks between charges.

These are just two of the possibilities raised by a novel supercapacitor design invented by material scientists at Vanderbilt University that is described in a paper published in the Oct. 22 issue of the journal Scientific Reports.

It is the first supercapacitor that is made out of silicon so it can be built into a silicon chip along with the microelectronic circuitry that it powers. In fact, it should be possible to construct these power cells out of the excess silicon that exists in the current generation of solar cells, sensors, mobile phones and a variety of other electromechanical devices, providing a considerable cost savings.

“If you ask experts about making a supercapacitor out of silicon, they will tell you it is a crazy idea,” said Cary Pint, the assistant professor of mechanical engineering who headed the development. “But we’ve found an easy way to do it.”

Instead of storing energy in chemical reactions the way batteries do, “supercaps” store electricity by assembling ions on the of a porous material. As a result, they tend to charge and discharge in minutes, instead of hours, and operate for a few million cycles, instead of a few thousand cycles like batteries.

These properties have allowed commercial , which are made out of activated carbon, to capture a few niche markets, such as storing energy captured by regenerative braking systems on buses and electric vehicles and to provide the bursts of power required to adjust of the blades of giant wind turbines to changing wind conditions. Supercapacitors still lag behind the electrical energy storage capability of lithium-ion batteries, so they are too bulky to power most consumer devices. However, they have been catching up rapidly.

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Research to improve the energy density of supercapacitors has focused on carbon-based nanomaterials like graphene and nanotubes. Because these devices store electrical charge on the surface of their electrodes, the way to increase their energy density is to increase the electrodes’ surface area, which means making surfaces filled with nanoscale ridges and pores.

“The big challenge for this approach is assembling the materials,” said Pint. “Constructing high-performance, functional devices out of nanoscale building blocks with any level of control has proven to be quite challenging, and when it is achieved it is difficult to repeat.”

So Pint and his research team – graduate students Landon Oakes, Andrew Westover and post-doctoral fellow Shahana Chatterjee – decided to take a radically different approach: using porous silicon, a material with a controllable and well-defined nanostructure made by electrochemically etching the surface of a silicon wafer.

This allowed them to create surfaces with optimal nanostructures for supercapacitor electrodes, but it left them with a major problem. Silicon is generally considered unsuitable for use in supercapacitors because it reacts readily with some of chemicals in the electrolytes that provide the ions that store the electrical charge.

With experience in growing carbon nanostructures, Pint’s group decided to try to coat the porous with carbon. “We had no idea what would happen,” said Pint. “Typically, researchers grow graphene from silicon-carbide materials at temperatures in excess of 1400 degrees Celsius. But at lower temperatures – 600 to 700 degrees Celsius – we certainly didn’t expect graphene-like material growth.”

When the researchers pulled the porous silicon out of the furnace, they found that it had turned from orange to purple or black. When they inspected it under a powerful scanning electron microscope they found that it looked nearly identical to the original material but it was coated by a layer of graphene a few nanometers thick.

When the researchers tested the coated material they found that it had chemically stabilized the silicon surface. When they used it to make supercapacitors, they found that the graphene coating improved energy densities by over two orders of magnitude compared to those made from uncoated and significantly better than commercial supercapacitors.

The graphene layer acts as an atomically thin protective coating. Pint and his group argue that this approach isn’t limited to graphene. “The ability to engineer surfaces with atomically thin layers of materials combined with the control achieved in designing porous materials opens opportunities for a number of different applications beyond energy storage,” he said.

“Despite the excellent device performance we achieved, our goal wasn’t to create devices with record performance,” said Pint. “It was to develop a road map for integrated energy storage. Silicon is an ideal material to focus on because it is the basis of so much of our modern technology and applications. In addition, most of the silicon in existing devices remains unused since it is very expensive and wasteful to produce thin wafers.”

Pint’s group is currently using this approach to develop that can be formed in the excess materials or on the unused back sides of and sensors. The supercapacitors would store excess the electricity that the generate at midday and release it when the demand peaks in the afternoon.

When the researchers tested the coated material they found that it had chemically stabilized the silicon surface. When they used it to make supercapacitors, they found that the graphene coating improved energy densities by over two orders of magnitude compared to those made from uncoated and significantly better than commercial supercapacitors.

The graphene layer acts as an atomically thin protective coating. Pint and his group argue that this approach isn’t limited to graphene. “The ability to engineer surfaces with atomically thin layers of materials combined with the control achieved in designing porous materials opens opportunities for a number of different applications beyond energy storage,” he said.

“Despite the excellent device performance we achieved, our goal wasn’t to create devices with record performance,” said Pint. “It was to develop a road map for integrated energy storage. Silicon is an ideal material to focus on because it is the basis of so much of our modern technology and applications. In addition, most of the silicon in existing devices remains unused since it is very expensive and wasteful to produce thin wafers.”

Pint’s group is currently using this approach to develop that can be formed in the excess materials or on the unused back sides of and sensors. The supercapacitors would store excess the electricity that the generate at midday and release it when the demand peaks in the afternoon.

When the researchers tested the coated material they found that it had chemically stabilized the silicon surface. When they used it to make supercapacitors, they found that the graphene coating improved energy densities by over two orders of magnitude compared to those made from uncoated and significantly better than commercial supercapacitors.

The graphene layer acts as an atomically thin protective coating. Pint and his group argue that this approach isn’t limited to graphene. “The ability to engineer surfaces with atomically thin layers of materials combined with the control achieved in designing porous materials opens opportunities for a number of different applications beyond energy storage,” he said.

“Despite the excellent device performance we achieved, our goal wasn’t to create devices with record performance,” said Pint. “It was to develop a road map for integrated energy storage. Silicon is an ideal material to focus on because it is the basis of so much of our modern technology and applications. In addition, most of the silicon in existing devices remains unused since it is very expensive and wasteful to produce thin wafers.”

Pint’s group is currently using this approach to develop that can be formed in the excess materials or on the unused back sides of and sensors. The supercapacitors would store excess the electricity that the generate at midday and release it when the demand peaks in the afternoon.

“All the things that define us in a modern environment require electricity,” said Pint. “The more that we can integrate power storage into existing and devices, the more compact and efficient they will become.”

Europe Launches Space Metal 3D Printing Project.


The European Space Agency has rolled out a new initiative to refine 3D printing techniques to make space-grade metal parts.

The project, called AMAZE, aims to spur innovations that could one day allow astronauts to print their own metal tools aboard the International Space Station or let engineers on the ground to print entire satellites.

3D printing, or additive manufacturing, builds solid objects from a series of layers, typically by melting powder or wire materials. This technique can produce complex structures with more flexibility and less waste than traditional manufacturing, which could translate into big cost and time savings. . [Photos: ESA’s AMAZE Space Metal 3D Printing Project.

Billed as the world’s largest metal 3D-printing project, ESA’s initiative brings together 28 industrial partners across the continent. AMAZE is short for Additive Manufacturing Aiming Towards Zero Waste and Efficient Production of High-Tech Metal Products.

“We want to build the best quality metal products ever made,” David Jarvis, ESA’s Head of New Materials and Energy Research, said in a statement when the project was unveiled last week at the London Science Museum.

The group is focusing on making space-quality components by using lasers, electron beams and even plasma to melt metal alloys, Jarvis explained. The project also aims to explore the possibility of combining strong and lightweight, but more exotic metals, such as tungsten, niobium and platinum, though these materials are expensive.

As part of the initiative, four pilot 3D printing-factories are being established in Germany, Italy, Norway and the United Kingdom. David wants to help standardize the technique and bring it to the mainstream, connecting key players in the metallic 3D printing business to develop a supply chain.

Titanium Printed Structure

ESA officials say innovations along the way to make 3D printers more viable for spacecraft could have benefits on Earth, leading to improvements in aircraft wings, jet engines and automotive systems.

ESA is hardly alone in its ambition to perfect metal 3D printing for the final frontier. Among several other NASA endeavors in additive manufacturing, the U.S. space agency recently completed a successful hot-fire test of the biggest 3D-printed rocket part built to date: an engine injector printed with nickel-chromium alloy powder.

There are several private and university-led efforts, too. Earlier this month, a group of students at the University of California, San Diego performed their first test of a 3D-printed engine made from cobalt chromium.

Vaccination Against Seasonal Influenza May Reduce the Risk of Cardiovascular Events.


For many people, getting a seasonal flu shot may help them avoid a week or more of misery. But for some individuals, especially those with heart disease, vaccination against influenza appears to help reduce the likelihood of major adverse cardiovascular events, such as heart attack and stroke.

Researchers, whose findings appear today in JAMA, found that receiving influenza vaccine was associated with a 36% lower risk of cardiovascular events compared with not being immunized against flu. For individuals with recent acute coronary syndrome, such as a heart attack or unstable angina, influenza vaccine was associated with a 55% lower risk of cardiovascular events within 12 months compared with those who had a recent acute coronary syndrome but did not receive the vaccine. The findings are based on a systematic review and meta-analysis involving 6 randomized clinical trials, 5 published and 1 unpublished. These trials collectively enrolled 6735 patients with a mean age of 67 years; 36% had a history of heart disease.

Lead author Jacob A. Udell, MD, MPH, of the University of Toronto in Canada, discusses his team’s findings.

news@JAMA: Why did you do the study?

Dr Udell: There have been reports suggesting that getting the flu shot was protective against heart attack and stroke, but most of these reports were observational. So we went back and systematically reviewed all clinical trials involving vaccine or placebo to see if this signal of cardioprotection was reproducible and consistent across the studies.

news@JAMA: What did you find?

Dr Udell: We found there was a 36% risk reduction overall for getting a cardiac event in those who were vaccinated compared with those who did not get the vaccine. We also found that those who had a heart attack had even more benefit. So in the higher-risk patients, the flu vaccine gave more benefit.

news@JAMA: Although your study cannot answer this question, can you speculate why influenza vaccination is associated with reduced heart risk?

Dr Udell: The flu may be a severe illness, causing a lot of inflammation, and that will have an effect on all your organs, including the heart and brain. This inflammation may also disrupt stable hardened arteries and free atherosclerotic plaque, causing a heart attack. Another theory is that the flu may push people over a tipping point, especially among the frail and elderly.

news@JAMA: So what would you tell others about the implications of your study findings for vaccination against influenza?

Dr Udell: For the skeptics out there, I’d note that we now have yet another reason why receiving influenza vaccine might be a beneficial thing to do. And those hospitalized with a heart attack should be vaccinated before they walk out the door so they don’t have care gaps that could be very dangerous.

Pillownauts Rest For Science.


Ah, the things we do for the sake of scientific inquiry. These volunteers for the European Space Agency just got out of bed for the first time in 21 days. To examine the effects of spaceflight on astronauts’ bodies, the “pillownauts” laid at a 6 degree angle with their feet up in a medical facility in Toulouse, France while scientists poked and prodded them for three weeks.

No bathrooms, no showers, no getting up for a quick stretch. The paid volunteers were subjected to a strict high-protein, high-salt diet and an exercise routine “that involves pushing the volunteers down onto vibrating plates while doing upside-down squats,” according to ESA. Researchers from the University of Bonne hypothesized that this diet and exercise routine might lessen the bone and muscle loss associated with long-term missions in microgravity. The crazy sci-fi headgear they’re wearing is designed to measure how much oxygen each person breathes in and how much carbon dioxide comes out, as a way to study the links between diet, breathing and energy consumption.

Child bone-marrow transplant ‘first’


First human trial of new bone-marrow transplant method.

Mohammed Ahmed
Mohammed started going to school in September

Doctors at London’s Great Ormond Street Hospital have carried out a pioneering bone-marrow transplant technique.

They say the method should help with donor shortages since it does not require a perfect cell match.

Mohammed Ahmed, who is nearly five years old, was among the first three children in the world to try out the new treatment.

He has severe combined immunodeficiency syndrome and had been waiting for a suitable donor for years.

Mohammed, who lives in Milton Keynes, was referred to Great Ormond Street Hospital when he was a year old.

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We waited for a full match but it did not come. By the grace of God, we took the decision to have the treatment”

Jamil Ahmed, Mohammed’s dad

His condition – a weak immune system – makes him more susceptible to infections than most, and a bone marrow transplant is the only known treatment.

While Mohammed was on the transplant waiting list, he became extremely sick with swine flu.

At that time, his doctors decided Mohammed’s only real hope was to have a mismatched bone-marrow transplant, with his father acting as the donor.

Mohammed’s dad, Jamil, agreed to give the experimental therapy a go.

Before giving his donation, Jamil was first vaccinated against swine flu so that his own bone-marrow cells would know how to fight the infection.

Mohammed’s doctors then modified these donated immune cells, called “T-cells”, in the lab to engineer a safety switch – a self-destruct message that could be activated if Mohammed’s body should start to reject them once transplanted.

Safety net

Rejection or graft-v-host disease is a serious complication of bone-marrow transplants, particularly where tissue matching between donor and recipient is not perfect, and is one of the most difficult challenges faced by patients and their doctors.

Mismatched transplants in children – where the donor is not a close match for the child – are usually depleted of T-cells to prevent graft-v-host disease, but this causes problems in terms of virus infections and leukaemia relapse.

Blood cells
White blood cells protect the body against infections

The safety switch gets round this – plenty of T-cells to be transfused and later killed off if problems do arise.

Thankfully, the transplant carried out in 2011 was a success – Mohammed’s doctors did not need to use the safety switch.

Although Mohammed still has to take a number of medicines to ward off future infections, his immune system is now in better shape.

Jamil said: “We waited for a full match but it did not come. By the grace of God, we took the decision to have the treatment.

“Now he is all right. Sometimes we forget what he has been through. We are just so grateful.”

He said Mohammed would still need close monitoring and regular health checks over the coming years, but his outlook was good.

Dr Waseem Qasim, ‎consultant in paediatric immunology at Great Ormond Street Hospital and lead author for the study, said the new approach should hopefully mean children who received a mismatched transplant could enjoy the same chance of success as those given a fully matched transplant.

“We think Mohammed is cured of his disorder. He should be able to lead a fairly normal life now.”

A full report about Mohammed’s therapy and the research by Great Ormond Street Hospital, King’s College London and the Institute of Child Health has just been published in PLoS One journal.

There are currently about 1,600 people in the UK waiting for a bone-marrow transplant and 37,000 worldwide.

Just 30% of people will find a matching donor from within their families.

Donations involve collecting blood from a vein or aspirating bone marrow from the pelvis using a needle and syringe.

Shorter Sleep Duration and Poorer Sleep Quality Linked to Alzheimer’s Disease Biomarker.


Poor sleep quality may impact Alzheimer’s disease onset and progression. This is according to a new study led by researchers at the Johns Hopkins Bloomberg School of Public Health who examined the association between sleep variables and a biomarker for Alzheimer’s disease in older adults. The researchers found that reports of shorter sleep duration and poorer sleep quality were associated with a greater β-Amyloid burden, a hallmark of the disease. The results are featured online in the October issue of JAMA Neurology.

“Our study found that among older adults, reports of shorter sleep duration and poorer sleep quality were associated with higher levels of β-Amyloid measured by PET scans of the brain,” said Adam Spira, PhD, lead author of the study and an assistant professor with the Bloomberg School’s Department of Mental Health. “These results could have significant public health implications as Alzheimer’s disease is the most common cause of dementia, and approximately half of older adults have insomnia symptoms.”

Alzheimer’s disease is an irreversible, progressive brain disease that slowly destroys memory and thinking skills. According to the National Institutes of Health, as many as 5.1 million Americans may have the disease, with first symptoms appearing after age 60. Previous studies have linked disturbed sleep to cognitive impairment in older people.

In a cross-sectional study of adults from the neuro-imagining sub-study of the Baltimore Longitudinal Study of Aging with an average age of 76, the researchers examined the association between self-reported sleep variables and β-Amyloid deposition. Study participants reported sleep that ranged from more than seven hours to no more than five hours. β-Amyloid deposition was measured by the Pittsburgh compound B tracer and PET (positron emission tomography) scans of the brain. Reports of shorter sleep duration and lower sleep quality were both associated with greater Αβ buildup.

“These findings are important in part because sleep disturbances can be treated in older people. To the degree that poor sleep promotes the development of Alzheimer’s disease, treatments for poor sleep or efforts to maintain healthy sleep patterns may help prevent or slow the progression of Alzheimer disease,” said Spira.  He added that the findings cannot demonstrate a causal link between poor sleep and Alzheimer’s disease, and that longitudinal studies with objective sleep measures are needed to further examine whether poor sleep contributes to or accelerates Alzheimer’s disease.

Bee brains challenge view that larger brains are superior at understanding conceptual relationships.


The humble honeybee may not seem very intelligent at first sight, but recent research has shown that it possesses a surprising degree of sophistication that is not expected in an insect brain. Specifically, the honeybee can understand conceptual relationships such as “same/different” and “above/below” that rely on relationships between objects rather than simply the physical features of objects.

In primates, this ability to understand conceptual relationships is attributed to neuronal activity in the prefrontal cortex (PFC). However, honeybees don’t have PFCs. Their brains are so small and lacking in complex brain structures that scientists have traditionally thought that the ability to understand conceptual relationships was beyond them.

Scientists Aurore Avarguès-Weber and Martin Giurfa, both from the University of Toulouse and CNRS in Toulouse, France, have analyzed the implications of the honeybee’s ability to understand conceptual relationships, and have published a paper on the subject in a recent issue of Proceedings of the Royal Society B.

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“One thing that should be clear from this analysis is that, although it is always a matter of debate what is unique to humans and what to animals, these results show at least something that is not,” Giurfa told Phys.org. “While the capacity of conceptual elaboration has been considered (and is still considered) a higher-order capacity proper from primates and other ‘highly-evolved’ animals (the quotes are ironic in this case), the fact that a 950 000-neuron [honeybee] brain can achieve this kind of task shows that the frontier does not reside there.

“The obvious question would be then, what brings as advantage a 100-billion-neuron [human] brain? Obviously several advantages can be cited: language, for instance. Consciousness, whose existence is a matter of debate and of investigation in animals. And the idea that human brains have perhaps replicated redundant and modifiable modules to solve problems that small brains solve with single microcircuits at a smaller scale.”

Nanodiamond production in ambient conditions opens door for flexible electronics, implants and more.


Instead of having to use tons of crushing force and volcanic heat to forge diamonds, researchers at Case Western Reserve University have developed a way to cheaply make nanodiamonds on a lab bench at atmospheric pressure and near room temperature.

The are formed directly from a gas and require no surface to grow on.

The discovery holds promise for many uses in technology and industry, such as coating plastics with ultrafine diamond powder and making flexible electronics, implants, drug-delivery devices and more products that take advantage of diamond’s exceptional properties.

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Their investigation is published today in the scientific journal Nature Communications. The findings build on a tradition of diamond research at Case Western Reserve.

Beyond its applications, the discovery may offer some insight into our universe: an explanation of how nanodiamonds seen in space and found in meteorites may be formed.

“This is not a complex process: ethanol vapor at and pressure is converted to diamond,” said Mohan Sankaran, associate professor of chemical engineering at Case Western Reserve and leader of the project. “We flow the gas through a plasma, add hydrogen and out come diamond nanoparticles. We can put this together and make them in almost any lab.”

The process for making these small “forever stones” won’t melt plastic so it is well suited for certain high-tech applications. Diamond, renowned for being hard, has excellent optical properties and the highest velocity of sound and thermal conductivity of any material.

Unlike the other form of carbon, graphite, diamond is a semiconductor, similar to silicon, which is the dominant material in the electronics industry, and gallium arsenide, which is used in lasers and other optical devices.

While the process is simple, finding the right concentrations and flows—what the researchers call the “sweet spot”—took time.

The other researchers involved were postdoctoral researcher Ajay Kumar, PhD student Pin Ann Lin, and undergraduate student Albert Xue, of Case Western Reserve; and physics professor Yoke Khin Yap and graduate student Boyi Hao, of Michigan Technical University.

Sankaran and John Angus, professor emeritus of chemical engineering, came up with the idea of growing nanodiamonds with no heat or pressure about eight years ago. Angus’ research in the 1960s and 1970s led him and others to devise a way to grow diamond films at low pressure and high temperature, a process known as chemical vapor deposition that is now used to make coatings on computer disks and razor blades. Sankaran’s specialty, meanwhile, is making nanoparticles using cool microplasmas.

It usually requires high pressures and high temperatures to convert graphite to diamond or a combination of hydrogen gas and a heated substrate to grow diamond rather than graphite.

“But at the nanoscale, surface energy makes diamond more stable than graphite,” Sankaran explained. “We thought if we could nucleate carbon clusters in the gas phase that were less than 5 nanometers, they would be diamond instead of graphite even at normal pressure and temperature.”

After several ups and downs with the effort, the process came together when Kumar joined Sankaran’s lab. The engineers produced diamond much like they’d produce carbon soot.

They first create a plasma, which is a state of matter similar to a gas but a portion is becoming charged, or ionized. A spark is an example of a plasma, but it’s hot and uncontrollable.

To get to cooler and safer temperatures, they ionized argon gas as it was pumped out of a tube a hair-width in diameter, creating a microplasma. They pumped ethanol—the source of carbon—through the microplasma, where, similar to burning a fuel, carbon breaks free from other molecules in the , and yields particles of 2 to 3 nanometers, small enough that they turn into diamond.

In less than a microsecond, they add hydrogen. The element removes carbon that hasn’t turned to diamond while simultaneously stabilizing the diamond particle surface.

The diamond formed is not the large perfect crystals used to make jewelry, but is a powder of diamond particles. Sankaran and Kumar are now consistently making high-quality diamonds averaging 2 nanometers in diameter.

The researchers spent about a year of testing to verify they were producing diamonds and that the process could be replicated, Kumar said. The team did different tests themselves and brought in Yap’s lab to analyze the nanoparticles by Raman spectroscopy.

Currently, nanodiamonds are made by detonating an explosive in a reactor vessel to provide heat and pressure. The diamond particles must then be removed and purified from contaminating elements massed around them. The process is quick and cheap but the nanodiamonds aggregate and are of varying size and purity.

The new research offers promising implications. Nanodiamonds, for instance, are being tested to carry drugs to tumors. Because diamond is not recognized as an invader by the immune system, it does not evoke resistance, the main reason why chemotherapy fails.

Sankaran said his nanodiamonds may offer an alternative to diamonds made by detonation methods because they are purer and smaller.

The group’s process produces three kinds of diamonds: about half are cubic, the same structure as gem , a small percentage are a form suspected of having hydrogen trapped inside and about half are lonsdaleite, a hexagonal form found in but rarely found on Earth.

A recent paper in the journal Physical Review Letters suggests that when interstellar dust collides, such high pressure is involved that the graphitic turns into londsdaleite nanodiamonds.

Sankaran and Kumar contend that an alternative with no high requirement, such as their method, should be considered, too.

“Maybe we’re making diamond in the way diamond is sometimes made in outer space,” Sankaran proposed. “Ethanol and plasmas exist in outer space, and our nanodiamonds are similar in size and structure to those found in space.”

The group is now investigating whether it can fine-tune the process to control which form of diamond is made, analyzing the structures and determining if each has different properties. Lonsdaleite, for instance, is harder than cubic diamond.

The researchers have made a kind of nanodiamond spray paint. “We can do this in a single step, by spraying the nanodiamonds as they are produced out of the plasma and purified with hydrogen, to coat a surface,” Kumar said.

And they are working on scaling up the process for industrial use.

“Will they be able to scale up? That’s always a crap shoot,” Angus said. “But I think it can be done, and at very high rates and cheaply. Ultimately, it may take some years to get there, but there is no theoretical reason it can’t be done.”

If the scaled-up process is as simple and cheap as the lab process, industry will find many applications for the product, Sankaran said.

Rheumatoid Arthritis: Painful Debilitating Disease More Devastating Than Previously Recognized.


Story at-a-glance

  • A revised and updated drug-free RA protocol based on a pioneering rheumatoid arthritis treatment tends to provide a 60-90 percent improvement rate in most RA sufferers
  • Important aspects of the treatment protocol include dietary modifications, low-dose Naltrexone, optimizing your vitamin D levels, astaxanthin, probiotics (preferably in the form of fermented foods), and getting regular exercise
  • Pain control is an important aspect of treating RA. Ideally, you’ll want to use the safest drugs and only when necessary, with the ultimate goal of managing your pain without medications. Some of the safest prescription drugs for pain are the non-acetylated salicylates, such as salsalate, sodium salicylate, and magnesium salicylate (i.e. Salflex, Disalcid, or Trilisate).
  • Rheumatoid arthritis affects about one percent of our population and at least two million Americans have definite or classical rheumatoid arthritis. This number has increased in recent years, as in 2010 about 2.5 percent of white women developed RA.

    It is a much more devastating illness than previously appreciated. Most patients with rheumatoid arthritis have a progressive disability.

    The natural course of rheumatoid arthritis is quite remarkable in that less than one percent of people with the disease have a spontaneous remission. Some disability occurs in 50-70 percent of people within five years after onset of the disease, and half will stop working within 10 years. The annual cost of this disease in the U.S. is estimated to be over $1 billion.

    This devastating prognosis is what makes this novel form of treatment so exciting, as it has a far higher likelihood of succeeding than the conventional approach.

    Over the years I have treated over 3,000 patients with rheumatic illnesses, including SLE, scleroderma, polymyositis and dermatomyositis.

    Approximately 15 percent of these patients were lost to follow-up for whatever reason and have not continued with treatment. The remaining patients seem to have a 60-90 percent likelihood of improvement on this treatment regimen.

    This level of improvement is quite a stark contrast to the typical numbers quoted above that are experienced with conventional approaches, and certainly a strong motivation to try the protocol I discuss below.

    Rheumatoid Arthritis Can Be Deadlier Than Heart Disease

    There is also an increased mortality rate with this disease. The five-year survival rate of patients with more than 30 joints involved is approximately 50 percent. This is similar to severe coronary artery disease or stage IV Hodgkin’s disease.

    Thirty years ago, one researcher concluded that there was an average loss of 18 years of life in patients who developed rheumatoid arthritis before the age of 50.

    Most authorities believe that remissions rarely occur. Some experts feel that the term “remission-inducing” should not be used to describe ANY current rheumatoid arthritis treatment, and a review of contemporary treatment methods shows that medical science has not been able to significantly improve the long-term outcome of this disease.

    Dr. Brown Pioneered a Novel Approach to Treat Rheumatoid Arthritis

    I first became aware of Doctor Brown’s protocol in 1989 when I saw him on 20/20 on ABC. This was shortly after the introduction of the first edition of his book, The Road Back.

    Unfortunately, Dr. Brown died from prostate cancer shortly after the 20/20 program, so I never had a chance to meet him.

    My application of Dr. Brown’s protocol has changed significantly since I first started implementing it. Initially, I rigidly followed Dr. Brown’s work with minimal modifications to his protocol.

    About the only change I made was changing Tetracycline to Minocin. I believe I was one of the first physicians who recommended the shift to Minocin, and most people who use his protocol now use Minocin.

    In 1939, Dr. Sabin, the discoverer of the polio vaccine, first reported chronic arthritis in mice caused by a mycoplasma. He suggested this agent might cause human rheumatoid arthritis. Dr. Brown worked with Dr. Sabin at the Rockefeller Institute.

    Dr. Brown was a board certified rheumatologist who graduated from Johns Hopkins medical school. He was a professor of medicine at George Washington University until 1970 where he served as chairman of the Arthritis Institute in Arlington, Virginia. He published over 100 papers in peer reviewed scientific literatureHe was able to help over 10,000 patients when he used this program, from the 1950s until his death in 1989, and clearly far more than that have been helped by other physicians using this protocol.

    He found that significant benefits from the treatment require, on average, about one to two years.

    I have treated nearly 3000 patients and find that the dietary modification I advocate, which I started to integrate in the early 1990s, accelerates the response rate to several months. I cannot emphasize strongly enough the importance of this aspect of the program.

    Still, the length of therapy can vary widely.

    In severe cases, it may take up to 30 months for patients to gain sustained improvement. One requires patience because remissions may take up to three to five years. Dr. Brown’s pioneering approach represents a safer, less toxic alternative to many conventional regimens and results of the NIH trial have finally scientifically validated this treatment.

    The dietary changes are absolutely an essential component of my protocol. Dr. Brown’s original protocol was notorious for inducing a Herxheimer, or worsening of symptoms, before improvement was noted. This could last two to six months. Implementing my nutrition plan resulted in a lessening of that reaction in most cases.

    When I first started using his protocol for patients in the late ’80s, the common retort from other physicians was that there was “no scientific proof” that this treatment worked. Well, that is certainly not true today. A review of the bibliography will provide over 200 references in the peer-reviewed medical literature that supports the application of Minocin in the use of rheumatic illnesses.

    In my experience, nearly 80 percent of people do remarkably better with this program. However, approximately five percent continue to worsen and require conventional agents, like methotrexate, to relieve their symptoms.

    Scientific Proof for This Approach

    The definitive scientific support for minocycline in the treatment of rheumatoid arthritis came with the MIRA trial in the United States. This was a double blind randomized placebo controlled trial done at six university centers involving 200 patients for nearly one year. The dosage they used (100 mg twice daily) was much higher and likely less effective than what most clinicians currently use.

    They also did not employ any additional antibiotics or nutritional regimens, yet 55 percent of patients improved. This study finally provided the “proof” that many traditional clinicians demanded before seriously considering this treatment as an alternative regimen for rheumatoid arthritis.

    Dr. Thomas Brown’s effort to treat the chronic mycoplasma infections believed to cause rheumatoid arthritis is the basis for this therapy. Dr. Brown believed that most rheumatic illnesses respond to this treatment. He and others used this therapy for SLE, ankylosing spondylitis, scleroderma, dermatomyositis, and polymyositis.

    Dr. Osler was one of the most well respected and prominent physicians of his time (1849- 1919), and many regard him as the consummate physician of modern times. An excerpt from a commentary on Dr. William Osler provides a useful perspective on application of alternative medical paradigms:

    Osler would caution us against the arrogance of believing that only our current medical practices can benefit the patient. He would realize that new scientific insights might emerge from as yet unproved beliefs. Although he would fight vigorously to protect the public against frauds and charlatans, he would encourage critical study of whatever therapeutic approaches were reliably reported to be beneficial to patients.

    Factors Associated with Your Success on This Program

    There are many variables associated with an increased chance of remission or improvement.

    • The younger you are, the greater your chance for improvement
    • The more closely you follow the nutrition plan, the more likely you are to improve and the less likely you are to have a severe flare-up. I now offer the Nutritional Typing Test for free, so please do not skip this essential step.
    • Smoking seems to be negatively associated with improvement
    • The longer you have had the illness and the more severe the illness, the more difficult it seems to treat

    Revised Antibiotic-Free Approach

    Although I used a revision of his antibiotic approach for nearly 10 years, my particular prejudice is to focus on natural therapies. The program that follows is my revision of this protocol that allows for a completely drug-free treatment of RA, which is based on my experience of treating over 3000 patients with rheumatic illnesses in my Chicago clinic.

    If you are interested in reviewing or considering Dr. Brown’s antibiotic approach, I have included a summary of his work and the evidence for it in the appendix.

    Crucial Lifestyle Changes

    Improving your diet using a combination of my nutritional guidelines, nutritional typing is crucial for your success. In addition, there are some general principles that seem to hold true for all nutritional types and these include:

    • Eliminating sugar, especially fructose, and most grains. For most people it would be best to limit fruit to small quantities
    • Eating unprocessed, high-quality foods, organic and locally grown if possible
    • Eating your food as close to raw as possible
    • Getting plenty high-quality, animal-based omega-3 fats. Krill oil seems to be particularly helpful here as it appears to be a more effective anti inflammatory preparation. It is particularly effective if taken concurrently with 4 mg of Astaxanthin, which is a potent antioxidant bioflavanoid derived from algae
    • Astaxanthin at 4 mg per day is particularly important for anyone placed on prednisone as Astaxanthin offers potent protection against cataracts and age related macular degeneration
    • Incorporating regular exercise into your daily schedule

    Early Emotional Traumas Are Pervasive in Those with Rheumatoid Arthritis

    With the vast majority of the patients I treated, some type of emotional trauma occurred early in their life, before the age their conscious mind was formed, which is typically around the age of 5 or 6. However, a trauma can occur at any age, and has a profoundly negative impact.

    If that specific emotional insult is not addressed with an effective treatment modality then the underlying emotional trigger will continue to fester, allowing the destructive process to proceed, which can predispose you to severe autoimmune diseases like RA later in life.

    In some cases, RA appears to be caused by an infection, and it is my experience that this infection is usually acquired when you have a stressful event that causes a disruption in your bioelectrical circuits, which then impairs your immune system.

    This early emotional trauma predisposes you to developing the initial infection, and also contributes to your relative inability to effectively defeat the infection.

    Therefore, it’s very important to have an effective tool to address these underlying emotional traumas. In my practice, the most common form of treatment used is called the Emotional Freedom Technique (EFT).

    Although EFT is something that you can learn to do yourself in the comfort of your own home, it is important to consult a well-trained professional to obtain the skills necessary to promote proper healing using this amazing tool.

    Vitamin D Deficiency Rampant in Those with Rheumatoid Arthritis

    The early part of the 21st century brought enormous attention to the importance and value of vitamin D, particularly in the treatment of autoimmune diseases like RA.

    From my perspective, it is now virtually criminal negligent malpractice to treat a person with RA and not aggressively monitor their vitamin D levels to confirm that they are in a therapeutic range of 65-80 ng/ml.

    This is so important that blood tests need to be done every two weeks, so the dose can be adjusted to get into that range. Most normal-weight adults should start at 10,000 units of vitamin D per day.

    If you are in the US, then Lab Corp is the lab of choice.

    For more detailed information on vitamin D, you can review my vitamin D resource page.

    Low-Dose Naltrexone

    One new addition to the protocol is low-dose Naltrexone, which I would encourage anyone with RA to try. It is inexpensive and non-toxic and I have a number of physician reports documenting incredible efficacy in getting people off of all their dangerous arthritis meds.

    Although this is a drug, and strictly speaking not a natural therapy, it has provided important relief and is FAR safer than the toxic drugs that are typically used by nearly all rheumatologists.

    Nutritional Considerations

    Limiting sugar is a critical element of the treatment program. Sugar has multiple significant negative influences on your biochemistry. First and foremost, it increases your insulin levels, which is the root cause of nearly all chronic disease. It can also impair your gut bacteria.

    In my experience if you are unable to decrease your sugar intake, you are far less likely to improve. Please understand that the number one source of calories in the US is high fructose corn syrup from drinking soda. One of the first steps you can take is to phase out all soda, and replace it with pure, clean water.

    Exercise for Rheumatoid Arthritis

    It is very important to exercise and increase muscle tone of your non-weight bearing joints. Experts tell us that disuse results in muscle atrophy and weakness. Additionally, immobility may result in joint contractures and loss of range of motion (ROM). Active ROM exercises are preferred to passive.

    There is some evidence that passive ROM exercises increase the number of white blood cells (WBCs) in your joints.

    If your joints are stiff, you should stretch and apply heat before exercising. If your joints are swollen, application of 10 minutes of ice before exercise would be helpful.

    The inflamed joint is very vulnerable to damage from improper exercise, so you must be cautious. People with arthritis must strike a delicate balance between rest and activity, and must avoid activities that aggravate joint pain. You should avoid any exercise that strains a significantly unstable joint.

    A good rule of thumb is that if the pain lasts longer than one hour after stopping exercise, you should slow down or choose another form of exercise. Assistive devices are also helpful1 to decrease the pressure on affected joints. Many patients need to be urged to take advantage of these. The Arthritis Foundation has a book, Guide to Independent Living, which instructs patients about how to obtain them.

    Of course, it is important to maintain good cardiovascular fitness as well. Walking with appropriate supportive shoes is another important consideration.

    If your condition allows, it would be wise to move toward a Peak Fitness program that is designed for reaching optimal health.

    It’s Important to Control Your Pain

    One of the primary problems with RA is controlling pain. The conventional treatment typically includes using very dangerous drugs like prednisone, methotrexate, and drugs that interfere with tumor necrosis factor, like Enbrel.

    The goal is to implement the lifestyle changes discussed above as quickly as possible, so you can start to reduce these toxic and dangerous drugs, which do absolutely nothing to treat the cause of the disease.

    However, pain relief is obviously very important, and if this is not achieved, you can go into a depressive cycle that can clearly worsen your immune system and cause the RA to flare.

    So the goal is to be as comfortable and pain free as possible with the least amount of drugs. The Mayo Clinic offers several common sense guidelines2 for avoiding pain by paying heed to how you move, so as to not injure your joints.

    Safest Anti-Inflammatories to Use for Pain

    Clearly the safest prescription drugs to use for pain are the non-acetylated salicylates such as:

    • Salsalate
    • Sodium salicylate
    • Magnesium salicylate (i.e., Salflex, Disalcid, or Trilisate)

    They are the drugs of choice if there is renal insufficiency, as they minimally interfere with anticyclooxygenase and other prostaglandins.

    Additionally, they will not impair platelet inhibition in those patients who are on an every-other-day aspirin regimen to decrease their risk for stroke or heart disease.

    Unlike aspirin, they do not increase the formation of products of lipoxygenase-mediated metabolism of arachidonic acid. For this reason, they may be less likely to cause hypersensitivity reactions. These drugs have been safely used in patients with reversible obstructive airway disease and a history of aspirin sensitivity.

    They are also much gentler on your stomach than the other NSAIDs and are the drug of choice if you have problems with peptic ulcer disease. Unfortunately, all these benefits are balanced by the fact that they may not be as effective as the other agents and are less convenient to take. You need to take 1.5-2 grams twice a day, and tinnitus, or ringing in your ear, is a frequent side effect.

    You need to be aware of this complication and know that if tinnitus does develop, you need to stop the drugs for a day and restart with a dose that is half a pill per day lower. You can repeat this until you find a dose that relieves your pain and doesn’t cause any ringing in your ears.

    If the Safer Anti-Inflammatories Aren’t Helping, Try This Next…

    If the non-acetylated salicylates aren’t helping, there are many different NSAIDs to try. Relafen, Daypro, Voltaren, Motrin, Naprosyn. Meclomen, Indocin, Orudis, and Tolectin are among the most toxic or likely to cause complications. You can experiment with them, and see which one works best for you.

    If cost is a concern, generic ibuprofen can be used at up to 800 mg per dose. Unfortunately, recent studies suggest this drug is more damaging to your kidneys.

    If you use any of the above drugs, though, it is really important to make sure you take them with your largest meal as this will somewhat moderate their GI toxicity and the likelihood of causing an ulcer.

    Please beware that they are much more dangerous than the antibiotics or non-acetylated salicylates.

    You should have an SMA blood test performed at least once a year if you are on these medications. In addition, you must monitor your serum potassium levels if you are on an ACE inhibitor as these medications can cause high potassium levels. You should also monitor your kidney function. The SMA will show any liver impairment the drugs might be causing.

    These medications can also impair prostaglandin metabolism and cause papillary necrosis and chronic interstitial nephritis. Your kidney needs vasodilatory prostaglandins (PGE2 and prostacyclin) to counterbalance the effects of potent vasoconstrictor hormones such as angiotensin II and catecholamines. NSAIDs decrease prostaglandin synthesis by inhibiting cyclooxygenase, leading to unopposed constriction of the renal arterioles supplying your kidney.

    Warning: These Drugs Massively Increase Your Risk for Ulcers

    The first non-aspirin NSAID, indomethacin, was introduced in 1963. Now more than 30 are available. Relafen is one of the better alternatives as it seems to cause less of an intestinal dysbiosis.

    You must be especially careful to monitor renal function periodically. It is important to understand and accept the risks associated with these more toxic drugs.

    Every year, they do enough damage to the GI tract to kill 2,000 to 4,000 people with rheumatoid arthritis alone. That is 10 people EVERY DAY. At any given time, 10 to 20 percent of all those receiving NSAID therapy have gastric ulcers.

    If you are taking an NSAID, you are at approximately three times greater risk for developing serious gastrointestinal side effects than those who don’t.

    Approximately 1.2 percent of patients taking NSAIDs are hospitalized for upper GI problems, per year of exposure. One study of patients taking NSAIDs showed that a life-threatening complication was the first sign of ulcer in more than half of the subjects.

    Researchers found that the drugs suppress production of prostacyclin, which is needed to dilate blood vessels and inhibit clotting. Earlier studies had found that mice genetically engineered to be unable to use prostacyclin properly were prone to clotting disorders.

    Anyone who is at increased risk of cardiovascular disease should steer clear of these medications. Ulcer complications are certainly potentially life-threatening, but heart attacks are a much more common and likely risk, especially in older individuals.

    How You Can Tell if You Are at Risk for NSAID Side Effects

    Risk factor analysis can help determine if you will face an increased danger of developing these complications. If you have any of the following, you will likely to have a higher risk of side effects from these drugs:

    1. Old age
    2. Peptic ulcer history
    3. Alcohol dependency
    4. Cigarette smoking
    5. Concurrent prednisone or corticosteroid use
    6. Disability
    7. Taking a high dose of the NSAID
    8. Using an NSAID known to be more toxic

    Prednisone

    The above drug class are called non steroidal anti inflammatories (NSAIDs). If they are unable to control the pain, then prednisone is nearly universally used. This is a steroid drug that is loaded with side effects.

    If you are on large doses of prednisone for extended periods of time, you can be virtually assured that you will develop the following problems:

    • Osteoporosis
    • Cataracts
    • Diabetes
    • Ulcers
    • Herpes reactivation
    • Insomnia
    • Hypertension
    • Kidney stones

    You can be virtually assured that every time you take a dose of prednisone your bones are becoming weaker. The higher the dose and the longer you are on prednisone, the more likely you are to develop the problems.

    However, if you are able to keep your dose to 5 mg or below, this is not typically a major issue.

    Typically this is one of the first medicines you should try to stop as soon as your symptoms permit.

    Beware that blood levels of cortisol peak between 3 and 9am. It would, therefore, be safest to administer the prednisone in the morning. This will minimize the suppression on your hypothalamic-pituitary-adrenal axis.

    You also need to be concerned about the increased risk of peptic ulcer disease when using this medicine with conventional non-steroidal anti-inflammatories. If you are taking both of these medicines, you have a 15 times greater risk of developing an ulcer!

    If you are already on prednisone, it is helpful to get a prescription for 1 mg tablets so you can wean yourself off the prednisone as soon as possible. Usually you can lower your dose by about 1 mg per week. If a relapse of your symptoms occurs, then further reduction of the prednisone is not indicated.

    How Do You Know When to Stop the Drugs?

    Unlike conventional approaches to RA, my protocol is designed to treat the underlying cause of the problem. So eventually the drugs that you are going to use during the program will be weaned off.

    The following criteria can help determine when you are in remission and can consider weaning off your medications:

    • A decrease in duration of morning stiffness to no more than 15 minutes
    • No pain at rest
    • Little or no pain or tenderness on motion
    • Absence of joint swelling
    • A normal energy level
    • A decrease in your ESR to no more than 30
    • A normalization of your CBC. Generally your HGB, HCT, & MCV will increase to normal and your “pseudo”-iron deficiency will disappear
    • ANA, RF, & ASO titers returning to normal

    If you discontinue your medications before all of the above criteria are met, there is a greater risk that the disease will recur.

    If you meet the above criteria, you can try to wean off your anti-inflammatory medication and monitor for flare-ups. If no flare-ups occur for six months, then discontinue the clindamycin.

    If the improvements are maintained for the next six months, you can then discontinue your Minocin and monitor for recurrences. If symptoms should recur, it would be wise to restart the previous antibiotic regimen.

    Evaluation to Determine and Follow Rheumatoid Arthritis

    If you have received evaluations and treatment by one or more board certified rheumatologists, you can be very confident that the appropriate evaluation was done. Although conventional treatments fail miserably in the long run, the conventional diagnostic approach is typically excellent, and you can start the treatment program discussed above.

    If you have not been evaluated by a specialist then it will be important to be properly evaluated to determine if indeed you have rheumatoid arthritis.

    Please be sure and carefully review Appendix Two, as you will want to confirm that fibromyalgia is not present.

    Beware that arthritic pain can be an early manifestation of 20-30 different clinical problems.

    These include not only rheumatic disease, but also metabolic, infectious and malignant disorders. Rheumatoid arthritis is a clinical diagnosis for which there is not a single test or group of laboratory tests that can be considered confirmatory.

    Criteria for Classification of Rheumatoid Arthritis

    • Morning Stiffness – Morning stiffness in and around joints lasting at least one hour before maximal improvement is noted.
    • Arthritis of three or more joint areas – At least three joint areas have simultaneously had soft-tissue swelling or fluid (not bony overgrowth) observed by a physician. There are 14 possible joints: right or left PIP, MCP, wrist, elbow, knee, ankle, and MTP joints.
    • Arthritis of hand joints – At least one joint area swollen as above in a wrist, MCP, or PIP joint.
    • Symmetric arthritis – Simultaneous involvement of the same joint areas (as in criterion 2) on both sides of your body (bilateral involvement of PIPs, MCPs, or MTPs) is acceptable without absolute symmetry. Lack of symmetry is not sufficient to rule out the diagnosis of rheumatoid arthritis.
    • Rheumatoid Nodules – Subcutaneous nodules over bony prominences, or extensor surfaces, or in juxta-articular regions, observed by a physician. Only about 25 percent of patients with rheumatoid arthritis develop nodules, and usually as a later manifestation.
    • Serum Rheumatoid Factor – Demonstration of abnormal amounts of serum rheumatoid factor by any method that has been positive in less than 5 percent of normal control subjects. This test is positive only 30-40 percent of the time in the early months of rheumatoid arthritis.

    You must also make certain that the first four symptoms listed in the table above are present for six or more weeks. These criteria have a 91-94 percent sensitivity and 89 percent specificity for the diagnosis of rheumatoid arthritis.

    However, these criteria were designed for classification and not for diagnosis. The diagnosis must be made on clinical grounds. It is important to note that many patients with negative serologic tests can have a strong clinical picture for rheumatoid arthritis.

    Your Hands Are the KEY to the Diagnosis of Rheumatoid Arthritis

    In a way, the hands are the calling card of rheumatoid arthritis. If you completely lack hand and wrist involvement, even by history, the diagnosis of rheumatoid arthritis is doubtful. Rheumatoid arthritis rarely affects your hips and ankles early in its course.

    The metacarpophalangeal joints, proximal interphalangeal and wrist joints are the first joints to become symptomatic. Osteoarthritis typically affects the joints that are closest to your fingertips (DIP joints) while RA typically affects the joints closest to your wrist (PIP), like your knuckles.

    Fatigue may be present before your joint symptoms begin, and morning stiffness is a sensitive indicator of rheumatoid arthritis. An increase in fluid in and around your joint probably causes the stiffness. Your joints are warm, but your skin is rarely red.

    When your joints develop effusions, hold them flexed at 5 to 20 degrees as it is likely going to be too painful to extend them fully.

    Radiological Changes

    Radiological changes typical of rheumatoid arthritis on PA hand and wrist X-rays, which must include erosions or unequivocal bony decalcification localized to, or most marked, adjacent to the involved joints (osteoarthritic changes alone do not count).

    Note: You must satisfy at least four of the seven criteria listed. Any of criteria 1-4 must have been present for at least 6 weeks. Patients with two clinical diagnoses are not excluded. Designations as classic, definite, or probable rheumatoid arthritis, are not to be made.

    Laboratory Evaluation

    The general initial laboratory evaluation should include a baseline ESR, CBC, SMA, U/A, 25 hydroxy D level and an ASO titer. You can also draw RF and ANA titers to further objectively document improvement with the therapy. However, they seldom add much to the assessment.

    Follow-up visits can be every two to four months depending on the extent of the disease and ease of testing.

    The exception here would be vitamin D testing, which should be done every two weeks until your 25 hydroxy D level is between 65 and 80 ng/ml.

    Many patients with rheumatoid arthritis have a hypochromic, microcytic CBC that appears very similar to iron deficiency, but it is not at all related. This is probably due to the inflammation in the rheumatoid arthritis impairing optimal bone marrow utilization of iron.

    It is important to note that this type of anemia does NOT respond to iron and if you are put on iron you will get worse, as the iron is a very potent oxidative stress. Ferritin levels are generally the most reliable indicator of total iron body stores. Unfortunately it is also an acute phase reactant protein and will be elevated anytime the ESR is elevated. This makes ferritin an unreliable test in patients with rheumatoid arthritis.

    Physicians Who Use This Protocol

    Roadback.org is the oldest organization promoting this work and the one Dr. Brown originally worked with.  They are an excellent resource to find health care professionals using this approach.

    APPENDIX ONE: The Infectious Cause of Rheumatoid Arthritis

    It is quite clear that autoimmunity plays a major role in the progression of rheumatoid arthritis. Most rheumatology investigators believe that an infectious agent causes rheumatoid arthritis. There is little agreement as to the involved organism, however.

    Investigators have proposed the following infectious agents:

    • Human T-cell lymphotropic virus Type I
    • Rubella virus
    • Cytomegalovirus
    • Herpesvirus
    • Mycoplasma

    This review will focus on the evidence supporting the hypothesis that mycoplasma is a common etiologic agent of rheumatoid arthritis.

    Mycoplasmas are the smallest self-replicating prokaryotes. They differ from classical bacteria by lacking rigid cell wall structures and are the smallest known organisms capable of extracellular existence. They are considered parasites of humans, animals, and plants.

    Culturing Mycoplasmas from Joints

    Mycoplasmas have limited biosynthetic capabilities and are very difficult to culture and grow from synovial tissues. They require complex growth media or a close parasitic relation with animal cells. This contributed to many investigators’ failure to isolate them from arthritic tissue.

    In reactive arthritis, immune complexes rather than viable organisms localize in your joints. The infectious agent is actually present at another site. Some investigators believe that the organism binding in the immune complex contributes to the difficulty in obtaining positive mycoplasma cultures.

    Despite this difficulty, some researchers have successfully isolated mycoplasma from synovial tissues of patients with rheumatoid arthritis. A British group used a leucocyte-migration inhibition test and found two-thirds of their rheumatoid arthritis patients to be infected with Mycoplasma fermentens. These results are impressive since they did not include more prevalent Mycoplasma strains like M salivarium, M ovale, M hominis, and M pneumonia.

    One Finnish investigator reported a 100 percent incidence of isolation of mycoplasma from 27 rheumatoid synovia using a modified culture technique. None of the non-rheumatoid tissue yielded any mycoplasmas.

    The same investigator used an indirect hemagglutination technique and reported mycoplasma antibodies in 53 percent of patients with definite rheumatoid arthritis. Using similar techniques, other investigators have cultured mycoplasma in 80-100 percent of their rheumatoid arthritis test population.

    Rheumatoid arthritis can also follow some mycoplasma respiratory infections.

    One study of over 1,000 patients was able to identify arthritis in nearly one percent of the patients. These infections can be associated with a positive rheumatoid factor. This provides additional support for mycoplasma as an etiologic agent for rheumatoid arthritis. Human genital mycoplasma infections have also caused septic arthritis.

    Harvard investigators were able to culture mycoplasma or a similar organism, ureaplasma urealyticum, from 63 percent of female patients with SLE and only four percent of patients with CFS. The researchers chose CFS, as these patients shared similar symptoms as those with SLE, such as fatigue, arthralgias, and myalgias.

    Animal Evidence for the Protocol

    The full spectrum of human rheumatoid arthritis immune responses (lymphokine production, altered lymphocyte reactivity, immune complex deposition, cell-mediated immunity, and development of autoimmune reactions) occurs in mycoplasma induced animal arthritis

    Investigators have implicated at least 31 different mycoplasma species.

    Mycoplasma can produce experimental arthritis in animals from three days to months later. The time seems to depend on the dose given, and the virulence of the organism.

    There is a close degree of similarity between these infections and those of human rheumatoid arthritis.

    Mycoplasmas cause arthritis in animals by several mechanisms. They either directly multiply within the joint or initiate an intense local immune response.

    Arthritogenic mycoplasmas also cause joint inflammation in animals by several mechanisms. They induce nonspecific lymphocyte cytotoxicity and antilymphocyte antibodies as well as rheumatoid factor.

    Mycoplasma clearly causes chronic arthritis in mice, rats, fowl, swine, sheep, goats, cattle, and rabbits. The arthritis appears to be the direct result of joint infection with culturable mycoplasma organisms.

    Gorillas have tissue reactions closer to man than any other animal, and investigators have shown that mycoplasma can precipitate a rheumatic illness in gorillas. One study demonstrated that mycoplasma antigens do occur in immune complexes in great apes.

    The human and gorilla IgG are very similar and express nearly identical rheumatoid factors (IgM anti-IgG antibodies). The study showed that when mycoplasma binds to IgG it can cause a conformational change. This conformational change results in an anti-IgG antibody, which can then stimulate an autoimmune response.

    The Science of Why Minocycline Is Used

    If mycoplasma were a causative factor in rheumatoid arthritis, one would expect tetracycline type drugs to provide some sort of improvement in the disease. Collagenase activity increases in rheumatoid arthritis and probably has a role in its cause.

    Investigators have demonstrated that tetracycline and minocycline inhibit leukocyte, macrophage, and synovial collagenase.

    There are several other aspects of tetracyclines that may play a role in rheumatoid arthritis. Investigators have shown minocycline and tetracycline to retard excessive connective tissue breakdown and bone resorption, while doxycycline inhibits digestion of human cartilage.

    It is also possible that tetracycline treatment improves rheumatic illness by reducing delayed-type hypersensitivity response. Minocycline and doxycycline both inhibit phosolipases, which are considered proinflammatory and capable of inducing synovitis.

    Minocycline is a more potent antibiotic than tetracycline and penetrates tissues better.

    These characteristics shifted the treatment of rheumatic illness away from tetracycline to minocycline. Minocycline may benefit rheumatoid arthritis patients through its immunomodulating and immunosuppressive properties. In vitro studies have demonstrated a decreased neutrophil production of reactive oxygen intermediates along with diminished neutrophil chemotaxis and phagocytosis.

    Minocycline has also been shown to reduce the incidence and severity of synovitis in animal models of arthritis. The improvement was independent of minocycline’s effect on collagenase.

    Minocycline has also been shown to increase intracellular calcium concentrations that inhibit T-cells.

    Individuals with the Class II major histocompatibility complex (MHC) DR4 allele seem to be predisposed to developing rheumatoid arthritis.

    The infectious agent probably interacts with this specific antigen in some way to precipitate rheumatoid arthritis. There is strong support for the role of T cells in this interaction.

    So minocycline may suppress rheumatoid arthritis by altering T cell calcium flux and the expression of T cell derived from collagen binding protein. Minocycline produced a suppression of the delayed hypersensitivity in patients with Reiter’s syndrome, and investigators also successfully used minocycline to treat the arthritis and early morning stiffness of Reiter’s syndrome.

    Clinical Studies

    In 1970, investigators at Boston University conducted a small, randomized placebo-controlled trial to determine if tetracycline would treat rheumatoid arthritis. They used 250 mg of tetracycline a day.

    Their study showed no improvement after one year of tetracycline treatment. Several factors could explain their inability to demonstrate any benefits.

    Their study used only 27 patients for a one-year trial, and only 12 received tetracycline, so noncompliance may have been a factor. Additionally, none of the patients had severe arthritis. Patients were excluded from the trial if they were on any anti-remittive therapy.

    Finnish investigators used lymecycline to treat the reactive arthritis in Chlamydia trachomatous infections. Their study compared the effect of the medication in patients with two other reactive arthritis infections: Yersinia and Campylobacter.

    Lymecyline produced a shorter course of illness in the Chlamydia induced arthritis patients, but did not affect the other enteric infections-associated reactive arthritis. The investigators later published findings that suggested lymecycline achieved its effect through non-antimicrobial actions. They speculated it worked by preventing the oxidative activation of collagenase.

    The first trial of minocycline for the treatment of animal and human rheumatoid arthritis was published by Breedveld. In the first published human trial, Breedveld treated 10 patients in an open study for 16 weeks. He used a very high dose of 400 mg per day. Most patients had vestibular side effects resulting from this dose.

    However, all patients showed benefit from the treatment, and all variables of efficacy were significantly improved at the end of the trial.

    Breedveld expanded on his initial study and later observed similar impressive results. This was a 26-week double-blind placebo-controlled randomized trial with minocycline for 80 patients.

    They were given 200 mg twice a day.

    The Ritchie articular index and the number of swollen joints significantly improved (p < 0.05) more in the minocyline group than in the placebo group.

    Investigators in Israel studied 18 patients with severe rheumatoid arthritis for 48 weeks.

    These patients had failed two other DMARD. They were taken off all DMARD agents and given minocycline 100 mg twice a day. Six patients did not complete the study — three withdrew because of lack of improvement, and three had side effects of vertigo or leukopenia.

    All patients completing the study improved. Three had complete remission, three had substantial improvement of greater than 50 percent, and six had moderate improvement of 25 percent in the number of active joints and morning stiffness.

    APPENDIX TWO: Make Certain You are Assessed for Fibromyalgia

    You need to be very sensitive to this condition when you have rheumatoid arthritis as it is frequently a complicating condition. Many times, the pain will be confused with a flare-up of the RA.

    You need to aggressively treat this problem. If it is ignored, the likelihood of successfully treating the arthritis is significantly diminished.

    Fibromyalgia is a very common problem. Some experts believe that five percent of people are affected with it. Over 12 percent of the patients at the Mayo Clinic’s Department of Physical

    Medicine and Rehabilitation have this problem, and it is the third most common diagnosis by rheumatologists in the outpatient setting. Fibromyalgia affects women five times as frequently as men.

    Signs and Symptoms of Fibromyalgia

    One of the main features of fibromyalgia is morning stiffness, fatigue, and multiple areas of tenderness in typical locations. Most people with fibromyalgia complain of pain over many areas of their body, with an average of six to nine locations. Although the pain is frequently described as being “all over,” it is most prominent in the neck, shoulders, elbows, hips, knees, and back.

    Tender points are generally symmetrical and on both sides of the body. The areas of tenderness are usually small (less than an inch in diameter) and deep within the muscle. They are often located in sites that are slightly tender in normal people.

    People with fibromyalgia, however, differ in having increased tenderness at these sites from the average person. Firm palpation with the thumb (just past the point where the nail turns white) over the outside elbow will typically cause a vague sensation of discomfort. Patients with fibromyalgia will experience much more pain and will often withdraw the arm involuntarily.

    More than 70 percent of patients describe their pain as profound aching and stiffness of muscles. Often it is relatively constant from moment to moment, but certain positions or movements may momentarily worsen the pain. Other terms used to describe the pain are “dull” and “numb.”

    Sharp or intermittent pain is relatively uncommon.

    Patients with fibromyalgia also often complain that sudden loud noises worsen their pain.

    The generalized stiffness of fibromyalgia does not diminish with activity, unlike the stiffness of rheumatoid arthritis, which lessens as the day progresses. Despite the lack of abnormal lab tests, patients can suffer considerable discomfort.

    The fatigue is often severe enough to impair activities of work and recreation. Patients commonly experience fatigue on arising and complain of being more fatigued when they wake up than when they went to bed.

    Over 90 percent of patients believe the pain, stiffness, and fatigue are made worse by cold, damp weather. Overexertion, anxiety, and stress are also factors.

    Many find that localized heat, such as hot baths, showers, or heating pads, give them some relief. There is also a tendency for pain to improve in the summer with mild activity, or with rest.

    Some patients will date the onset of their symptoms to some initiating event. This is often an injury, such as a fall, a motor vehicle accident, or a vocational or sports injury. Others find that their symptoms began with a stressful or emotional event, such as a death in the family, a divorce, a job loss, or similar occurrence.

    Pain Location

    Patients with fibromyalgia have pain in at least 11 of the following 18 tender point sites (one on each side of the body):

    1. Base of the skull where the suboccipital muscle inserts
    2. Back of the low neck (anterior intertransverse spaces of C5-C7)
    3. Midpoint of the upper shoulders (trapezius)
    4. On the back in the middle of the scapula
    5. On the chest where the second rib attaches to the breastbone (sternum)
    6. One inch below the outside of each elbow (lateral epicondyle)
    7. Upper outer quadrant of buttocks
    8. Just behind the swelling on the upper leg bone below the hip (trochanteric prominence)
    9. The inside of both knees (medial fat pads proximal to the joint line)

    Fibromyalgia pain sites

    Treatment of Fibromyalgia

    There is a persuasive body of emerging evidence that indicates that patients with fibromyalgia are physically unfit in terms of sustained endurance. Some studies show that exercise can decrease fibromyalgia pain by 75 percent.

    Sleep is also critical to improvement, and many times, improved fitness will also correct the sleep disturbance.

    Normalizing vitamin D levels has also been shown to be helpful to decrease pain as has topical magnesium oil supplementation.

    Allergies, especially to mold, seem to be another common cause of fibromyalgia. There are some simple interventions using techniques called Total Body Modification (TBM). Call 800-243-4826.

    APPENDIX THREE: Antibiotic Therapy with Minocin

    There are three different tetracyclines available: simple tetracycline, doxycycline, or Minocin (minocycline).

    Minocin has a distinct and clear advantage over tetracycline and doxycycline in three important areas:

    1. Extended spectrum of activity
    2. Greater tissue penetrability
    3. Higher and more sustained serum levels

    Bacterial cell membranes contain a lipid layer. One mechanism of building up a resistance to an antibiotic is to produce a thicker lipid layer. This layer makes it difficult for an antibiotic to penetrate. Minocin’s chemical structure makes it the most lipid soluble of all the tetracyclines.

    This difference can clearly be demonstrated when you compare the drugs in the treatment of two common clinical conditions.

    Minocin gives consistently superior clinical results in the treatment of chronic prostatitis. In other studies, Minocin was used to improve 75-85 percent of patients whose acne had become resistant to tetracycline. Strep is also believed to be a contributing cause to many patients with rheumatoid arthritis. Minocin has shown significant activity against treatment of this organism.

    Important Factors to Consider When Using Minocin

    Unlike the other tetracyclines, Minocin tends not to cause yeast infections. Some infectious disease experts even believe that it has a mild anti-yeast activity. Women can be on this medication for several years and not have any vaginal yeast infections. Nevertheless, it would be prudent to take prophylactic oral lactobacillus acidophilus and bifidus preparations.

    This will help to replace the normal intestinal flora that is killed with the Minocin.

    Another advantage of Minocin is that it tends not to sensitize you to the sun. This minimizes your risk of sunburn and increased risk of skin cancer.

    However, you must incorporate several precautions with the use of Minocin.

    Like other tetracyclines, food impairs its absorption. However, the absorption is much less impaired than with other tetracyclines. This is fortunate because some people cannot tolerate Minocin on an empty stomach and have to take it with a meal to avoid GI side effects.

    If you need to take it with a meal, you will still absorb 85 percent of the medication, whereas tetracycline is only 50 percent absorbed. In June of 1990, a pelletized version of Minocin also became available, which improved absorption when taken with meals.

    This form is only available in the non-generic Lederle brand, and is a more than reasonable justification to not substitute for the generic version.

    Clinical experience has shown that many patients will relapse when they switch from the brand name to the generic. In February, 2006 Wyeth sold manufacturing rights of Minocin to Triax Pharmaceuticals (866-488-7429).

    Clinically, it has been documented that it is important to take Lederle brand Minocin as most all generic minocycline are clearly less effective.

    A large percentage of patients will not respond at all, or not do as well with generic non-Lederle minocycline.

    Traditionally it was recommended to only receive the brand name Lederle Minocin. However, there is one generic brand that is acceptable, and that is the brand made by Lederle. The only difference between Lederle generic Minocin and brand name Minocin is the label and the price.

    The problem is finding the Lederle brand generic. Some of my patients have been able to find it at Wal Mart. Since Wal Mart is one of the largest drug chains in the US, this should make the treatment more widely available for a reduced charge.

    Many patients are on NSAID’s that contribute to microulcerations of the stomach, which cause chronic blood loss. It is certainly possible to develop a peptic ulcer contributing to this blood loss.

    In either event, patients are frequently receiving iron supplements to correct their blood counts.

    IT IS IMPERATIVE THAT MINOCIN NOT BE GIVEN WITH IRON!

    Over 85 percent of the dose will bind to the iron and pass through your colon unabsorbed.

    If iron is taken, it should be at least one hour before Minocin, or two hours after.

    A recent, uncommon, complication of Minocin is a cell-mediated hypersensitivity pneumonitis.

    Most patients can start on 100 mg of Minocin every Monday, Wednesday, and Friday evening. Doxycycline can be substituted for patients who cannot afford the more expensive Minocin.

    It is important to not give either medication daily, as this does not seem to provide as great a clinical benefit.

    WARNING: Tetracycline type drugs can cause a permanent yellow-grayish brown discoloration of your teeth.

    This can occur in the last half of pregnancy, and in children up to eight years old. You should not routinely use tetracycline in children.

    If you have severe disease, you can consider increasing the dose to as high as 200 mg three times a week. Aside from the cost of this approach, several problems may result from the higher doses.

    Minocin can cause quite severe nausea and vertigo, but taking the dose at night tends to decrease this problem considerably.

    However, if you take the dose at bedtime, you must swallow the medication with TWO glasses of water. This is to insure that the capsule doesn’t get stuck in your throat. If that occurs, a severe chemical esophagitis can result, which can send you to the emergency room.

    For those physicians who elect to use tetracycline or doxycycline for cost or sensitivity reasons, several methods may help lessen the inevitable secondary yeast overgrowth. Lactobacillus acidophilus will help maintain normal bowel flora and decrease the risk of fungal overgrowth.

    Aggressive avoidance of all sugars, especially those found in non-diet sodas, will also decrease the substrate for the yeast’s growth. Macrolide antibiotics like Biaxin or Zithromax may be used if tetracyclines are contraindicated.

    They would also be used in the three pills a week regimen.

    Clindamycin

    The other drug used to treat rheumatoid arthritis is clindamycin. Dr. Brown’s book discusses the uses of intravenous clindamycin, and it is important to use the IV form of treatment if the disease is severe.

    In my experience nearly all scleroderma patients require a more aggressive stance and use of IV treatment. Scleroderma is a particularly dangerous form of rheumatic illness that should receive aggressive intervention.

    A major problem with the IV form is the cost. The price ranges from $100 to $300 per dose if administered by a home health care agency. However, if purchased directly from Upjohn, significant savings can be had.

    If you have a milder illness, the oral form of clindamycin is preferable.

    With a mild rheumatic illness (the minority of cases), it is even possible to exclude this from your regimen. Initial starting doses for an adult would be a 1,200 mg dose once a week.

    Please note that many people do not seem to tolerate this medication as well as Minocin. The major complaint seems to be a bitter metallic type taste, which lasts about 24 hours after the dose.

    Taking the dose after dinner does seem to help modify this complaint somewhat. If this is a problem, you can lower the dose and gradually increase the dose over a few weeks.

    Concern about the development of C. difficile pseudomembranous enterocolitis as a result of the clindamycin is appropriate. This complication is quite rare at this dosage regimen, but it certainly can occur.

    It is also important to be aware of the possibility of developing a severe and uncontrollable bout of diarrhea. Administration of acidophilus seems to limit this complication by promoting the growth of the healthy gut flora.

    If you have a resistant form of rheumatic illness, intravenous administration should be considered. Generally, weekly doses of 900 mg are administered until clinical improvement is observed.

    This generally occurs within the first 10 doses.

    At that time, the regimen can be decreased to every two weeks with the oral form substituted on the weeks where the IV is not taken.

    What to Do if You Fail to Respond

    The most frequent reason for failure to respond to the protocol is lack of adherence to the dietary guidelines.

    Most people eat too many grains and sugars, which disturbs insulin physiology. It is important that you adhere as strictly as possible to the guidelines.

    A small minority, generally under 15 percent of patients, will fail to respond to the protocol described above, despite rigid adherence to the diet. These individuals should already be on the IV clindamycin.

    It appears that hyaluronic acid, which is a potentiating agent commonly used in the treatment of cancer, may be quite useful in these cases. It seems that hyaluronic acid has very little to no direct toxicity but works in a highly synergistic fashion when administered directly in the IV bag with the clindamycin.

    Hyaluronic acid is also used in orthopedic procedures. The dose is generally from 2 to 10 cc into the IV bag. Hyaluronic acid is not inexpensive, however, as the cost may range up to $10 per cc. You also need to use some caution, as it may precipitate a significant Herxheimer flare reaction.