New findings rejuvenate age-old drug development field.

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On the internet, antiaging therapies abound. Longevity clinics peddle supplements and growth hormones. They advertise vitamin cocktails and antioxidant-rich diets. They offer chelation therapy. People who’ve tried such treatments talk glowingly of renewed vigor and rejuvenation. But none of these therapies have been shown definitively to make people live longer or dramatically improve health. Some can even cause harm.

The scientific literature contains even more experimental age-fighting therapies that have yet to fulfill their promise. That doesn’t mean the quest has been in vain, however. Over the past two decades, researchers have identified several pathways that seem to play a key part in longevity. The hope is that these pathways will lead to new drug treatments that slow the aging process and ward off age-related diseases such as cancer and Alzheimer’s.

But bringing therapies from the lab to the clinic won’t be easy. Here, Nature Medicine looks at the three of the most talked-about lines of investigation among scientists in the aging community.

Counting calories

Perhaps the surest path to longevity in lab models involves calorie restriction. Cutting calories seems to lengthen lifespans for protozoa, yeast, flies, worms, fish and mice. However, the data in primates are mixed. A 20-year study by researchers at the Wisconsin National Primate Research Center in Madison showed that calorie restriction could extend the lives of rhesus monkeys¹. But cutting calories failed to provide any survival benefit to monkeys in a 25-year study conducted at the US National Institute on Aging (NIA) Laboratory of Experimental Gerontology in Dickerson, Maryland². Why that might be isn’t entirely clear.

Demonstrating that calorie restriction extends age in humans will be even more difficult, considering the length and cost of such a trial. So, researchers have instead looked at the effects of calorie restriction on health outcomes that have been linked to aging, including body temperature, metabolic rate, inflammatory markers and insulin resistance. In 2007, the NIA funded three laboratories to look into some of these markers. The two-year study, which included 220 nonobese participants and wrapped up last year, compared a typical diet with one that curbed calories by 25%.

Trial results were scheduled to be released late last month (after Nature Medicine went to press) at the annual Experimental Biology meeting in Boston. The trial investigators, including Eric Ravussin, an obesity researcher at the Pennington Biomedical Research Center in Baton Rouge, Louisiana, declined to provide specifics ahead of time, although Ravussin says: “We reproduced a lot of the observations shown with caloric restriction in rodents.”

Rich Miller, associate director for research at the University of Michigan’s Geriatrics Center in Ann Arbor, sees no reason why calorie restriction shouldn’t extend longevity in humans, but it still may not be a feasible antiaging approach. In a world filled with a plethora of finger-licking combinations of fat, salt and sugar, few people would choose to cut their caloric intake by a quarter. Nonetheless, caloric restriction research has helped point researchers toward promising molecular pathways.

Sirtuins in the spotlight

One such mediator of caloric restriction is a family of proteins called sirtuins. Just over a decade ago, Leonard Guarente and his colleagues at the Massachusetts Institute of Technology in Cambridge showed that calorie restriction extends the lifespan of yeast, but the effect wasn’t present in mutants that lacked one of the sirtuin proteins, Sir2 (ref. 3). Guarente’s lab had already linked Sir2 to longevity in yeast, and this new research suggested a mechanism.

A media frenzy erupted in 2006 when a team led by one of Guarante’s former trainees, David Sinclair, a molecular biologist at Harvard Medical School in Boston, reported that a chemical found in red wine, known as resveratrol, appeared to make overweight mice live longer by activating SIRT1, the mammalian equivalent of Sir2 (ref. 4). The idea that swilling red wine might be the path to longer life was tantalizing, but Sinclair’s research soon came under fire. Some questioned whether the mouse model his team used was appropriate. Others couldn’t replicate parts of Sinclair’s results.

Sinclair published a rebuttal to the naysayers earlier this year in which his team outlined a proposed molecular pathway through which resveratrol acts⁵. Yet, even if resveratrol does in fact activate SIRT1, it does not seem to help healthy mice that aren’t obese live longer, according to two studies that supplemented standard mouse chow with varying doses of resveratrol beginning at 12 months of age^6,⁷. “We tried two different doses at three different labs,” says David Harrison from the Jackson Laboratory in Bar Harbor, Maine, who led one of the studies as part of the NIA-funded Interventions Testing Program (ITP). “There was absolutely no hint of an effect.”

Sinclair admits that resveratrol is not very potent. “I do believe that we can do better,” he says. Sirtris Pharmaceuticals, a company Sinclair helped found in 2006 that was purchased by the UK drug giant GlaxoSmithKline two years later, has already developed several compounds designed to modulate SIRT1 that are structurally distinct from resveratrol. The lead candidate, SRT2104, has been tested in a phase 1 trial and seems to be safe⁸. Whether it will also prove effective in people still remains to be seen.

Rapamycin on trial

Although resveratrol failed to have an effect in normal mice, another immune-suppressing drug called rapamycin emerged victorious from the ITP. “To everyone’s delight, it had a big effect, the biggest effect of any of the compounds we’ve tested so far,” Harrison says. Administering rapamycin to mice in their food starting at nine months of age increased median survival by at least two months on average in males and about twice that in females⁷. Similar age extensions were seen in mice exposed to rapamycin from 20 months of age⁹. If rapamycin worked as well in humans as it did in these mice, “it would give us about ten more years of healthy lifespan,” Harrison says.

However, the effects weren’t all positive. The mice that received rapamycin had more severe cataracts and greater testicular damage than the control mice¹⁰. The drug, which is currently approved to prevent rejection in organ transplant recipients, also tends to increase the risk of infectious diseases and diabetes in people. So, physicians are reluctant to give rapamycin or any of its many mimics, known as rapalogs, to otherwise healthy individuals.

A study published last year by Joseph Baur, of the University of Pennsylvania Perelman School of Medicine in Philadelphia, and David Sabatini, of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, suggests there may be a way to separate the good effects from some of the bad. Rapamycin inhibits the protein mTOR, short for mammalian target of rapamycin, which exists as part of two separate complexes, mTORC1 and mTORC2. Rapamycin’s beneficial effects appear to be due to inhibition of mTORC1. However, Baur’s and Sabatini’s research suggests that the drug also disrupts mTORC2, and that this disruption may explain the insulin resistance seen in mice¹¹. A compound that targets only mTORC1 might have fewer side effects.

New leases on life

Aging researchers continue to test other potential life-extending compounds with demonstrated safety profiles. For example, Harrison and his ITP colleagues recently gave mice green tea extract, a component of the spice turmeric, a triglyceride commonly found in coconut oil and other health supplements with purported longevity benefits that are known to be safe in people, but they didn’t see any effect on life span in the animals¹². Now on the researchers’ plate is metformin, a drug used to treat type 2 diabetes. At an aging conference in San Antonio last year, Rafael de Cabo and his colleagues from the NIA reported that a low dose of metformin extended the lifespan of mice. A high dose, however, was toxic.

Developing an antiaging pill with absolutely no side effects may simply be unrealistic, notes Matt Kaeberlein, an aging researcher at the University of Washington in Seattle. “There are reasons why these mutations that slow aging are generally not selected for in nature,” he says. “They have costs associated with them.” How hefty those costs might be and whether society will be willing to pay them remains a question for the ages.

Source:Nature

Living labs open door to retirees who want to join studies.

Posted by zedie

Despite the fact that the elderly account for the greatest proportion of patients for certain ailments, they are often underrepresented in medical research. In addition to explicit exclusion criteria included in many trials, scientists and drug companies are often loath to include senior citizens in their studies because of the myriad logistical challenges that old age presents. Elderly individuals might not have the mobility to travel to investigational sites, and they’re often less willing to switch physicians from the ones they’ve come to know and trust.

To encourage more participation in research among the over-65 crowd, an independent living facility at the Mayo Clinic in Rochester, Minnesota, is now trying to rethink what a study site has to look like.

On the fourth floor of a 21-story residential building, Mayo researchers have built a ‘living lab’ that spans 51,000 square feet and includes two mock-up apartments and rooms for convening focus groups. A small section on the floor above houses treadmills, electrocardiographs and other devices to measure physiology. Beyond simply bringing health studies closer to the elderly residents of the building, the research space has substantial built-in video recording infrastructure, allowing improved observation of how certain products and test ideas fare.

The combined space, known as the Healthy Aging and Independent Living (HAIL) lab, was established in 2011 at a retirement home called Charter House, which is affiliated with—and physically connected to—Mayo. In the past couple years, the HAIL lab has partnered with companies such as General Mills, United Healthcare and Best Buy to look at, for example, the acceptance of technology by the elderly. For now, the endeavor is concentrated on projects that are simple or observational, such as user feedback on products and exploring how video game participation might influence health in the elderly. However, “in the next five years, clinical trials with pharmacological agents might be forthcoming,” says Nicholas LaRusso, director of the Mayo Clinic Center for Innovation.

The vision of providing improved health research for the elderly is shared by another HAIL partner, the Good Samaritan Society, the largest nonprofit provider of senior care and services in the US. In an ongoing independent 1,200-person study at 5 of its 240 senior care facilities, the Good Samaritan Society is looking at the benefit of motion sensor technology. It has thus far found that the technology can detect repeat trips to the bathroom, which could indicate a urinary tract infection.

Kelly Soyland, director of innovation at the Sioux Falls, South Dakota–based society, says that his team has started exploring the idea of more traditional clinical research at some of their facilities at some point down the road: “We’re building the organizational capacity to work in that formal research space.”

Source: Nature

Dengue deluge highlights need for vaccine.

Posted by zedie

The global health burden of dengue could be much higher than previously thought. In modeling work published, a team led by Simon Hay, an epidemiologist at the University of Oxford, UK, estimated that 390 million people around the world were infected with the mosquito-borne virus in 2010, a figure more than three times greater than that given by the World Health Organization.

Only around a quarter of all the dengue cases were ‘apparent’—requiring medical treatment or making people miss work or school—so the findings are unlikely to greatly affect clinical practice. However, the large number of previously unrecognized people with mild or asymptomatic infections could have an impact on future mosquito control efforts or vaccination campaigns. “The bigger the problem, the more important become any efforts to prevent it,” says Donald Shepard, a health policy researcher at Brandeis University in Waltham, Massachusetts, who studies dengue.

Source: Nature

Japan to offer fast-track approval path for stem cell therapies.

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A retooling of Japan’s drug authorization framework, on its way to becoming law, could produce the world’s fastest approval process specifically designed for regenerative medicine. “I don’t know of any other countries that have broken out with a separate and novel system” for cellular therapies, says University College London regenerative medicine expert Chris Mason, who recently met with Japanese policymakers to discuss the law.

Japan has recently been trying to shake its ‘drug lag’, a term used to describe its historically slow review process that sometimes translates into therapies reaching the market well after they have received the green light elsewhere. But the country is now ready to speed the translation of regenerative medicine to the bedside.

The move comes in response to the potential offered by its homegrown induced pluripotent stem (iPS) cell technology, which netted Shinya Yamanaka, of the University of Kyoto, last year’s Nobel Prize in Medicine or Physiology. The government already flooded the field with more than 20 billion yen ($206 million) in a supplementary budget announced earlier this year, and it’s expected to allocate another 90 billion yen into the sector over the coming decade.

Under the Pharmaceutical Affairs Law as it currently stands, regenerative therapies, like small-molecule drugs, must undergo three phases of costly and cumbersome clinical trials to get approval by Japan’s Pharmaceutical and Medical Devices Agency.

The proposed amendments to the pharmaceutical law will create a new, separate approval channel for regenerative medicine. Rather than using phased clinical trials, companies will have to demonstrate efficacy in pilot studies of as few as ten patients in one study, if the change is dramatic enough, or a few hundred when improvement is more marginal. According to Toshio Miyata, deputy director of the Evaluation and Licensing Division at the Pharmaceutical and Food Safety Bureau in Tokyo, if efficacy can be “surmised,” the treatment will be approved for marketing. At that stage, the treatment could be approved for commercial use and, crucially for such expensive treatments, for national insurance coverage.

Phased out

With the bar for regenerative therapies dramatically lowered by requiring only limited safety and efficacy data—and essentially doing away with the need for high-powered phase 3 trials—the amendments’ architects say it will be possible to get a stem cell treatment to the market in just three years, rather than the typical six or more. The law should also give local producers of regenerative medicine an edge even over those selling stem cell therapies in South Korea, where an accelerated system has helped companies get more stem cell treatments on the market than any other country (see Nat. Med. 18, 329, 2012). “It’s bold,” says Yoshihide Esaki, director of Bio-Industry Division, a bureau of the Ministry of Economy, Trade and Industry based in Tokyo, which promoted legislation calling for the update.

Following approval, there will be a post-market surveillance period of five to seven years, after which the treatment will be evaluated again for safety and efficacy. Every patient must be entered in a registry during that period, says Miyata. If the therapies prove inefficacious or unsafe, approval can be withdrawn.

Doug Sipp worries whether post-market surveillance will turn up relevant data. Sipp, who studies regulatory issues related to stem cells at the RIKEN Center for Developmental Biology in Kobe, Japan, says that making people who receive the therapies during this period cough up even the 30% co-pay generally required under Japan’s national insurance plan “will essentially be asking patients to pay for the privilege of serving as the subjects of medical experiments.” And since the patients are paying, the studies cannot be randomized or blinded. Paying patients are also more likely to experience placebo effects, Sipp warns.

“There’s also the opportunity costs to patients,” who might be able to find better therapies elsewhere, adds Mason. “We have to make sure these therapies are safe and effective. Otherwise these regulatory routes are going to be closed.”

Despite these concerns, passage of the pre-vetted law is almost a given. Esaki says there’s a 50% chance the Japanese parliament will pass the law during the current session, ending in June. If so, it would go into effect next April. If not, scientists might have to wait until November 2014 or as late as April 2015.

Source: Nature

Painful Debilitating Disease More Devastating than Previously Recognized.

Posted by zedie

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 1 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 1 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.

RA Can Be More Deadly than Heart Disease

There is also an increased mortality rate with this disease. The five-year survival rate of patients with more than thirty 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 RA

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 his 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 literature.

He 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 1990’s, 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 3 to 5 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 5 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 ten 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 RA

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 RA

The early part of the 21^st 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 ten 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 helpful 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 towards 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 guidelines 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 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 prostacycline) 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 ten peopleEVERY 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:

Old age
Peptic ulcer history
Alcohol dependency
Cigarette smoking
Concurrent prednisone or corticosteroid use
Disability
Taking a high dose of the NSAID
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 RA

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 which 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 RA

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 to be 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 1000 patients was able to identify arthritis in nearly 1 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 4 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 ten 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 5 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 than 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):

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

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) 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:

Extended spectrum of activity
Greater tissue penetrability
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 between 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 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 1200 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.

Source: mercola.com

Beepocalypse Redux: Honeybees Are Still Dying — and We Still Don’t Know Why.

Posted by zedie

The honeybees are dying — and we don’t really know why. That’s the conclusion of a massive Department of Agriculture (USDA) report that came out late last week on colony-collapse disorder (CCD), the catchall term for the large-scale deaths of honeybee groups throughout the U.S. And given how important honeybees are to the food that we eat — bees help pollinate crops that are worth more than $200 billion a year — the fact that they are dying in large numbers, and we can’t say why, is very, very worrying.

CCD was first reported in 2006, when commercial beekeepers began noticing that their adult worker honeybees would suddenly flee the hive, ending up dead somewhere else and leading to the rapid loss of the colony. On normal years, commercial beekeepers might expect to lose 10% to 15% of their colony, but over the past five years, mortality rates for commercial operations in the U.S. have ranged from 28% to 33%. Since 2006 an estimated 10 million beehives worth about $200 each have been lost, costing beekeepers some $2 billion. There are now 2.5 million honeybee colonies in the U.S., down from 6 million 60 years ago. And if CCD continues, the consequences for the agricultural economy — and even for our ability to feed ourselves — could be dire. “Currently, the survivorship of honeybee colonies is too low for us to be confident in our ability to meet the pollination demands of U.S. agricultural crops,” the USDA report said.

So what’s causing CCD — and how can we stop it?

The problem is that there doesn’t seem to be a single smoking gun behind CCD. The USDA report points at a range of possible causes, including:

A parasitic mite called Varroa destructor that has often been found in decimated colonies
Several viruses
A bacterial disease called European foulbrood that is increasingly being detected in U.S. bee colonies
The use of pesticides, including neonicotinoids, a neuroactive chemical

Since CCD isn’t so much a single disease as it is a collection of symptoms, chances are that some or all of these factors, working in concert, might be behind the disappearance of the honeybees. The presence of the Varroa mite, for instance, can worsen the impact of existing viruses, while the stress of shipping bees back and forth across the country — increasingly common in commercial beekeeping — may be amplifying the stress on the insects and leaving them more vulnerable to CCD. (If you think a cross-country flight is rough on you, just imagine what it’s like for a honeybee hive.) The fact that CCD is increasingly seen in other countries as well gives more weight to the notion that there may be multiple factors at work.

Still, environmentalists have focused most on the potential role of pesticides — especially the powerful neonicotinoids — and some lab studies have found that the chemicals can adversely affect bee health. It’s not that the pesticides — which are aimed at other insects — are killing the bees outright, but rather that sublethal exposure in nectar and pollen may be interfering with the honeybees’ internal radar, preventing them from gathering pollen and returning safely to the hive.

The USDA report mostly withholds judgment on neonicotinoids, citing the need for more research, and the Environmental Protection Agency is conducting a very slow review of the evidence. Last week, though, the E.U., which is also grappling with CCD, decided it was done waiting, and announced a two-year ban on neonicotinoids. The European Commission enacted the ban on the recommendation of the European Food Safety Authority, which said in January that the pesticides should be restricted until scientists had cleared the chemicals of a role in CCD.

The chemical industry, unsurprisingly, disputes the finding. Bayer CropScience, a major pesticide manufactuer, said in a statement after the ban was announced:

As a science-based company, Bayer CropScience is disappointed that clear scientific evidence has taken a backseat in the decisionmaking process. This disproportionate decision is a missed opportunity to reach a solution that takes into consideration all of the existing product-stewardship measures and broad stakeholder concerns. The further reduction of effective crop-protection products will put at risk farmers’ ability to tackle important pests that can severely restrict their ability to grow high-quality food.

As Brad Plumer pointed out over at the Washington Post, it’s not that the E.U. necessarily has more evidence about the role that the chemicals might be playing in CCD. This is a classic case of policymaking by the precautionary principle. The pesticides are considered guilty until proven innocent, and so they’re preventively banned, even before the scientific case is rock solid. That’s not unusual for European environmental regulation, especially in regard to chemicals. In the U.S. it’s the reverse — before the federal government is likely to take the step of banning a class of pesticides, and pissing off the multibillion-dollar chemical industry, you’re likely to see a lot more science done.

So what we may get in Europe and the U.S. is a de facto field test of the real impact of neonicotinoids on CCD. In two years, if American bees are still dying and their European cousins are thriving, we might just have our answers. And if not, well, I hope you don’t like cashews, beets, broccoli, cabbage, brussels sprouts, chestnuts, watermelons, cucumber, fennel, strawberries, macadamia, mangoes, apricots, almonds or any of the other dozens of food crops pollinated by our hardworking, six-legged, unpaid farmworkers.

Source: Time.com

Five Worst Foods for Sleep.

Posted by zedie

Nearly 41 million US adults are sleeping just six hours or less each night, putting them at risk of adverse health effects (such as heart disease and obesity) and potentially fatal drowsy driving linked to lack of sleep.¹

While stress is one of the most-often cited reasons why people can’t sleep, there’s another factor that could be keeping you up at night: your diet. Certain foods can significantly interfere with your sleep, including the five worst of the worst below.

What Are the Five Worst Foods for Sleep?

1. Alcohol

A drink or two before bed can make you drowsy, leading many to believe it’s actually beneficial for sleep. But while it may make you nod off quicker, research shows that drinking alcohol makes you more likely to wake during the night, leaving you feeling less rested in the morning.

The latest study found that alcohol increases slow-wave “deep” sleep during the first half of the night, but then increases sleep disruptions in the second half of the night.²

Since alcohol is a potent muscle relaxant, it can also increase your risk of snoring. Snorers — and their bed partners — often experience restless sleep leading to sleepiness and difficulty concentrating during the day.

2. Coffee

Coffee, of course, is one of the most common sources of caffeine. This stimulant has a half-life of five hours, which means 25% of it will still be in your system even 10 hours later, and 12.5% 20 hours later (see the problem?). Plus, in some people caffeine is not metabolized efficiently, leaving you feeling its effects even longer after consumption. So, an afternoon cup of coffee or tea will keep some people from falling asleep at night. Be aware that some medications contain caffeine as well (for example, diet pills).

3. Dark Chocolate

Dark chocolate, though the healthiest form of chocolate from an antioxidant perspective, can contain relatively high levels of caffeine that can keep you up at night if you’re sensitive. It also contains theobromine, a compound that has caffeine-like effects.

4. Spicy Foods

Spicy foods before bedtime can give you indigestion that makes it nearly impossible to get a good night’s sleep. But even if you can eat spicy foods without discomfort, they are still linked with more time spent awake during the night and taking longer to fall asleep.³ It’s speculated that this may be due to capsaicin, an active ingredient in chili peppers, affecting sleep via changes in body temperature.

5. Unhealthy Fatty Foods

When you don’t get enough sleep, you’re more likely to crave high-fat, high-sugar foods the next day. But eating a high-fat diet also has impacts on your sleep, including leading to more fragmented sleep. In fact, an animal study revealed that eating fatty foods may lead to disrupted sleep and excessive daytime sleepiness.⁴

The link may be due to the brain chemical hypocretin, a neurotransmitter that helps keep you awake and also plays a role in managing appetite. Keep in mind that while you should limit your intake of unhealthy fats like those from fried foods, healthy fats (including saturated fats) play an important role in your diet and shouldn’t be eliminated.

Recent Study Gives Clues on How Diet Impacts Sleep

The link between what you eat and how well you sleep, and vice versa, is only beginning to be explored, however, a recent study evaluating the diets and sleep patterns of more than 4,500 people did find distinct dietary patterns among short and long sleepers.⁵

While the study was only able to generate hypotheses about dietary nutrients that may be associated with short and long sleep durations, it did yield some interesting data.

Very short sleepers (less than 5 hours a night): Had the least food variety, drank less water and consumed fewer total carbohydrates and lycopene (an antioxidant found in fruits and vegetables).
Short sleepers (5-6 hours): Consumed the most calories but ate less vitamin C and selenium, and drank less water. Short sleepers tended to eat more lutein and zeaxanthin than other groups.
Normal sleepers (7-8 hours): Had the most food variety in their diet, which is generally associated with a healthier way of eating.
Long sleepers (9 or more hours): Consumed the least calories as well as less theobromine (found in chocolate and tea), choline and total carbs. Long sleepers tended to drink more alcohol.

As for what the data means, researchers aren’t yet sure, but it could be that eating a varied diet is one key to normal, healthful sleep. If you need some help in this area, check out my nutrition plan for a step-by-step guide to optimizing your eating habits.

Sleep Tip: Stop Eating at Least Three Hours Before You Go to Bed

It is ideal to avoid eating any food three hours before bed, as this will optimize your blood sugar, insulin and leptin levels and contribute to overall good health and restful sleep. Specifically, avoiding food for at least three hours before bed will lower your blood sugar during sleep and help minimize damage from too much sugar floating around. Additionally, it will jumpstart the glycogen depletion process so you can shift to fat-burning mode.

A recent study⁶ is a powerful confirmation of this recommendation, as it found that the mere act of altering your typical eating habits — such as getting up in the middle of the night for a snack — causes a certain protein to desynchronize your internal food clock, which can throw you off kilter and set a vicious cycle in motion. Eating too close to bedtime, or very late at night when you’d normally be sleeping, may throw off your body’s internal clock and lead to weight gain.

Routinely eating at the wrong time may not only disrupt your biological clock and interfere with your sleep, but it may also devastate vital body functions and contribute to disease.

That said, while you’ve likely heard the advice that breakfast is the most important meal of the day, some experts believe that skipping breakfast and eating your main meal at night may actually be more in-tune with your innate biological clock. I’ve revised my own eating schedule to eliminate breakfast and restrict the time I eat to a period of about six to seven hours each day, which is typically from noon to 6 or 7 pm.

Diet Is Only One Factor in Getting a Good Night’s Sleep

There are many variables that impact how well you sleep. I suggest you read through my full set of 33 healthy sleep guidelines for all of the details, but to start, making some adjustments to your sleeping area can go a long way to ensure uninterrupted, restful sleep.

Cover your windows with blackout shades or drapes to ensure complete darkness. Even the tiniest bit of light in the room can disrupt your pineal gland’s production of melatonin and the melatonin precursor serotonin, thereby disrupting your sleep cycle.

So close your bedroom door, get rid of night-lights, and refrain from turning on any light during the night, even when getting up to go to the bathroom. If you have to use a light, install so-called “low blue” light bulbs in your bedroom and bathroom. These emit an amber light that will not suppress melatonin production.

Keep the temperature in your bedroom at or below 70 degrees F (21 degrees Celsius). Many people keep their homes and particularly their upstairs bedrooms too warm. Studies show that the optimal room temperature for sleep is quite cool, between 60 to 68 degrees F (15.5 to 20 C). Keeping your room cooler or hotter can lead to restless sleep.
Check your bedroom for electro-magnetic fields (EMFs). These can also disrupt your pineal gland’s production of melatonin and serotonin, and may have other negative effects as well. To do this, you need a gauss meter. You can find various models online, starting around $50 to $200. Some experts even recommend pulling your circuit breaker before bed to kill all power in your house.
Move alarm clocks and other electrical devices away from your head. If these devices must be used, keep them as far away from your bed as possible, preferably at least three feet.
Reduce use of light-emitting technology, such as your TV, iPad, and computer, before going to bed. These emit the type of light that will suppress melatonin production, which in turn will hamper your ability to fall asleep, as well as increase your cancer risk (melatonin helps to suppress harmful free radicals in your body and slows the production of estrogen, which can contribute to cancer). Ideally, you’ll want to turn all such light-emitting gadgets off at least one hour prior to bedtime.

Source: mercola.com

Ultrasound Guidance Significantly Lowers Risk for Failed Lumbar Punctures and Epidural Catheterizations.

Posted by zedie

The failure rate was 1% with ultrasound and 7% with standard palpation of landmarks.

Lumbar puncture (LP) is performed for diagnostic purposes (e.g., analysis of cerebrospinal fluid [CSF]) and for drug delivery, and epidural catheterization is performed to administer anesthetics. But sometimes these procedures fail. In this meta-analysis of 17 randomized, controlled trials involving 1300 patients, investigators determined whether ultrasound (US)-guided imaging, compared with standard palpation of anatomical landmarks, can lower risk for failed LPs or epidural catheterizations.

Five studies evaluated LP and nine evaluated epidural catheterization. Failed LP was defined as lack of CSF return; failed epidural catheterization was defined as inability to place an epidural catheter, need for intraoperative analgesia, or need to replace the catheter. Overall, 1% of procedures failed in the US group, compared with 7% in the standard-technique group. US-guided imaging was associated with significantly lower risk for both failed LP and failed epidural catheterization (risk ratio, 0.20 for each). Likewise, US-guided imaging significantly reduced the number of traumatic procedures (defined as “visible blood aspiration or a red blood cell count” in the CSF), insertion attempts, and needle redirections.

Comment: Unsurprisingly, use of ultrasound-guided imaging during lumbar puncture and epidural catheterization decreased the chances of adverse outcomes. The authors conclude that US-guided imaging could “be a useful adjunct” for these procedures, particularly in settings where they are commonly performed (e.g., obstetrics) or “where failure is associated with particularly negative consequences” (e.g., pediatrics).

Source: Journal Watch General Medicine

Real-world data at ARVO highlight transformational outcomes seen with Lucentis®, including lower injection frequency than in original clinical trials.

Posted by zedie

UK real world study shows 59% reduction of legal blindness attributable to wet AMD since introduction of Lucentis with 9.7 injections spread over 5 years
New one year REPAIR data shows visual acuity improvement of 14 letters with an average of 3.6 Lucentis injections in myopic CNV patients
Largest Lucentis meta-analysis, over 10,000 patients, confirms well-established safety profile reported from extensive clinical trials and real-world experience

Novartis has reported that new data with the eye drug Lucentis® (ranibizumab), first licensed in June 2006, is highlighted in a total of 209 abstracts at the 2013 Association for Research in Vision and Ophthalmology (ARVO) annual meeting this week. This research across multiple retinal disease areas, including wet age-related macular degeneration (AMD), diabetic macular edema (DME), retinal vein occlusion (RVO) and myopic choroidal neovascularization (CNV), demonstrates that Lucentis with a wealth of real world long term experience is the pioneering anti-VEGF ocular treatment with its transformational efficacy, individualized treatment regimen, and well established long-term safety profile.

“Lucentis was designed to save sight and this is further demonstrated by the wealth of data in multiple disease areas reported at ARVO this week. In patients with myopic CNV average VA gains were 14 letters with an average of 3.6 injections,” said Dr Timothy Wright, Global Head Development, Novartis Pharma AG. “Real world evidence shows a lower number of injections and clinic visits than in the original studies with Lucentis, whilst achieving an over 50 percent reduction of blindness due to wet AMD.”

Lucentis ARVO highlights include:
Real world evidence in wet AMD: One study looked at how Lucentis treatment impacted the rates of legal blindness secondary to wet AMD in Scotland, UK. Blind registration data from the Royal National Institute for the Blind was retrospectively analyzed. It was reported that since the commencement of treatment with Lucentis there was a 59% reduction in the incidence rate of legal blindness attributable to wet AMD. The mean number of clinic visits decreased by year, with 9.0 in year one, 5.8 in year two, 4.8 in year three, 2.3 in year four and 0.5 in year five; the average number of injections was 9.7 spread over 5 years. This study highlights how the transformational efficacy of Lucentis translates into clinical real-world practice[1]. [Oral session 118]

DME: The response rates were evaluated in patients with DME in the RESTORE trial. Patients were treated with Lucentis 0.5 mg (monotherapy or combined with laser) or laser alone for a duration of 12 months, at 12 months all patients were eligible for Lucentis 0.5mg as-needed and the study was extended to 36 months. The patients who responded better to Lucentis treatment were the ones who were more recently diagnosed with DME, highlighting the need for prompt therapy[2]. [Poster session 290]

Myopic CNV: In the prospective, multicenter trial of Lucentis in myopic CNV patients, the REPAIR study, the primary endpoint was the mean gain in letters from baseline visual acuity at 12 months. At month 12 the mean visual acuity gain was 13.8 letters, this was achieved with a low number of injections to month 12 (mean 3.6, median 3) with 21% patients requiring only the one baseline treatment[3]. [Poster session 314]

Safety profile of Lucentis: In the largest comprehensive evaluation of Lucentis safety data to date, a meta-analysis examining the systemic safety profile of Lucentis across 22 studies and 10,300 patients, the safety profile of was reported to be consistent with that from individual randomized, controlled clinical trials[4]. [Poster session 234]

LUMINOUS, a 5-year, global, prospective, observational, long-term study to evaluate the safety and effectiveness of Lucentis 0.5 mg across its licensed indications is being conducted. This global study, approximately 500 centers in 34 countries worldwide, aims to enroll 30,000 patients. The baseline characteristics of the first cohort of patients enrolled were as expected and are representative of patients from a real-world setting[5]. [Poster session 375]

About Lucentis® (ranibizumab)
Lucentis is a humanized therapeutic antibody fragment designed to block all biologically active forms of vascular endothelial cell growth factor-A (VEGF-A). Increased levels of VEGF-A are seen in wet AMD and other ocular diseases such as diabetic macular edema (DME) and retinal vein occlusion (RVO). Lucentis was specifically designed for the eye, minimizing systemic exposure.

Lucentis is licensed for the treatment of wet AMD in more than 100 countries, in more than 90 countries for the treatment of visual impairment due to DME and in 90 countries for visual impairment due to macular edema secondary to RVO, including both branch- and central-RVO. Novartis submitted regulatory approval for Lucentis for the treatment of myopic CNV in the European Union in the third quarter of 2012. In many countries, including those in Europe, Lucentis has an individualized treatment regimen with the goal of maximizing visual outcomes while minimizing under- or over-treating patients.

Novartis and Alcon sponsor the eXcellence in Ophthalmology Vision Award (XOVA). XOVA is an annual award launched in 2010 that provides funding to non-profit initiatives and projects that will have a positive impact on improving the quality of eye care and make a significant impact in addressing unmet needs in the fields of ophthalmology and optometry.

Lucentis has a well-established safety profile supported by 43 extensive sponsored clinical studies and real-world experience. Its safety profile has been well established in a clinical development program that enrolled more than 12,500 patients across indications and there is more than 1.7 million patient-treatment years of exposure since its launch in the United States in 2006.

Lucentis was developed by Genentech and Novartis. Genentech has the commercial rights to Lucentis in the United States. Novartis has exclusive rights in the rest of the world. Lucentis is a registered trademark of Genentech Inc.

Source: Novartis newsletter

The Nobel Peace Prize 1901.

Posted by zedie

Biography

Jean Henry Dunant‘s life (May 8, 1828-October 30, 1910) is a study in contrasts. He was born into a wealthy home but died in a hospice; in middle age he juxtaposed great fame with total obscurity, and success in business with bankruptcy; in old age he was virtually exiled from the Genevan society of which he had once been an ornament and died in a lonely room, leaving a bitter testament. His passionate humanitarianism was the one constant in his life, and theRed Cross his living monument.

The Geneva household into which Henry Dunant was born was religious, humanitarian, and civic-minded. In the first part of his life Dunant engaged quite seriously in religious activities and for a while in full-time work as a representative of the Young Men’s Christian Association, traveling in France, Belgium, and Holland.

When he was twenty-six, Dunant entered the business world as a representative of the Compagnie genevoise des Colonies de Sétif in North Africa and Sicily. In 1858 he published his first book, Notice sur la Régence de Tunis [An Account of the Regency in Tunis], made up for the most part of travel observations but containing a remarkable chapter, a long one, which he published separately in 1863, entitled L’Esclavage chez les musulmans et aux États-Unis d’Amérique [Slavery among the Mohammedans and in the United States of America].

Having served his commercial apprenticeship, Dunant devised a daring financial scheme, making himself president of the Financial and Industrial Company of Mons-Gémila Mills in Algeria (eventually capitalized at 100,000,000 francs) to exploit a large tract of land. Needing water rights, he resolved to take his plea directly to Emperor Napoleon III. Undeterred by the fact that Napoleon was in the field directing the French armies who, with the Italians, were striving to drive the Austrians out of Italy, Dunant made his way to Napoleon’s headquarters near the northern Italian town of Solferino. He arrived there in time to witness, and to participate in the aftermath of, one of the bloodiest battles of the nineteenth century. His awareness and conscience honed, he published in 1862 a small book Un Souvenir de Solférino [A Memory of Solferino], destined to make him famous.

A Memory has three themes. The first is that of the battle itself. The second depicts the battlefield after the fighting – its «chaotic disorder, despair unspeakable, and misery of every kind» – and tells the main story of the effort to care for the wounded in the small town of Castiglione. The third theme is a plan. The nations of the world should form relief societies to provide care for the wartime wounded; each society should be sponsored by a governing board composed of the nation’s leading figures, should appeal to everyone to volunteer, should train these volunteers to aid the wounded on the battlefield and to care for them later until they recovered. On February 7, 1863, the Société genevoise d’utilité publique [Geneva Society for Public Welfare] appointed a committee of five, including Dunant, to examine the possibility of putting this plan into action. With its call for an international conference, this committee, in effect, founded the Red Cross. Dunant, pouring his money and time into the cause, traveled over most of Europe obtaining promises from governments to send representatives. The conference, held from October 26 to 29, with thirty-nine delegates from sixteen nations attending, approved some sweeping resolutions and laid the groundwork for a gathering of plenipotentiaries. On August 22, 1864, twelve nations signed an international treaty, commonly known as the Geneva Convention, agreeing to guarantee neutrality to sanitary personnel, to expedite supplies for their use, and to adopt a special identifying emblem – in virtually all instances a red cross on a field of white¹.

Dunant had transformed a personal idea into an international treaty. But his work was not finished. He approved the efforts to extend the scope of the Red Cross to cover naval personnel in wartime, and in peacetime to alleviate the hardships caused by natural catastrophes. In 1866 he wrote a brochure called the Universal and International Society for the Revival of the Orient, setting forth a plan to create a neutral colony in Palestine. In 1867 he produced a plan for a publishing venture called an «International and Universal Library» to be composed of the great masterpieces of all time. In 1872 he convened a conference to establish the «Alliance universelle de l’ordre et de la civilisation» which was to consider the need for an international convention on the handling of prisoners of war and for the settling of international disputes by courts of arbitration rather than by war.

The eight years from 1867 to 1875 proved to be a sharp contrast to those of 1859-1867. In 1867 Dunant was bankrupt. The water rights had not been granted, the company had been mismanaged in North Africa, and Dunant himself had been concentrating his attention on humanitarian pursuits, not on business ventures. After the disaster, which involved many of his Geneva friends, Dunant was no longer welcome in Genevan society. Within a few years he was literally living at the level of the beggar. There were times, he says², when he dined on a crust of bread, blackened his coat with ink, whitened his collar with chalk, slept out of doors.

For the next twenty years, from 1875 to 1895, Dunant disappeared into solitude. After brief stays in various places, he settled down in Heiden, a small Swiss village. Here a village teacher named Wilhelm Sonderegger found him in 1890 and informed the world that Dunant was alive, but the world took little note. Because he was ill, Dunant was moved in 1892 to the hospice at Heiden. And here, in Room 12, he spent the remaining eighteen years of his life. Not, however, as an unknown. After 1895 when he was once more rediscovered, the world heaped prizes and awards upon him.

Despite the prizes and the honors, Dunant did not move from Room 12. Upon his death, there was no funeral ceremony, no mourners, no cortege. In accordance with his wishes he was carried to his grave «like a dog»³.

Dunant had not spent any of the prize monies he had received. He bequeathed some legacies to those who had cared for him in the village hospital, endowed a «free bed» that was to be available to the sick among the poorest people in the village, and left the remainder to philanthropic enterprises in Norway and Switzerland.

Source: Nobel Prize.org

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APPENDIX ONE: The Infectious Cause of Rheumatoid Arthritis

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What Are the Five Worst Foods for Sleep?

Recent Study Gives Clues on How Diet Impacts Sleep

Sleep Tip: Stop Eating at Least Three Hours Before You Go to Bed

Diet Is Only One Factor in Getting a Good Night’s Sleep

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