Dan Roden, left, and Dan Masys are studying how genetic

information embedded in patients’ electronic medical records

may help improve treatment outcomes.


GoogleNews.com, January 7, 2010  —  More than five years in development, Vanderbilt University’s DNA databank, called BioVU, is now open for business.

Late last month Vanderbilt researchers gained access to one of the largest repositories of its kind to conduct genetic studies of human disease and drug response.

“This is a resource for discovery,” said Dan Roden, assistant vice chancellor for personalized medicine. “The next step is to actually use this information in the care of patients.”

Genetic variations can increase the risk of developing certain diseases. They also explain why certain medications don’t work in some patients and can cause serious, sometimes life-threatening effects in others.

Finding these associations requires sophisticated genetic studies. That’s why BioVU and the computer-driven technologies developed by Vanderbilt’s Department of Biomedical Informatics are so powerful – they combine the twin scientific revolutions in genomics and informatics.

In 2007, BioVU began extracting DNA from blood samples of adult patients at Vanderbilt that otherwise would be discarded. To date it has acquired nearly 75,000 DNA samples, linked to their matching electronic medical records.

Both the samples and the records are “de-identified,” meaning that all personal information has been stripped away to guarantee patients’ anonymity. BioVU will begin receiving samples from pediatric patients later this year, and ultimately it will contain biological samples from 250,000 individuals.

BioVU is carefully reviewed to ensure it meets ethical standards for research. The “consent-to-treat” form for Vanderbilt patients includes a box that allows them to “opt out” of the databank.

Only Vanderbilt researchers can apply as principal investigators to use BioVU, although their collaborators can be from other centers. As of late December, two research applications had been approved by Vanderbilt’s Institutional Review Board (IRB).

One of the projects, Vanderbilt Electronic Systems for Pharmacogenomic Assessment, will test whether variations in patients’ DNA could have predicted their responses to certain medications. If so, genetic information embedded in the electronic medical record could help improve treatment outcomes and avoid adverse drug effects.

Roden said the development of “personalized medicine” requires excellence in translational science and informatics. “Our leadership at the very top … (has) really been committed to this,” he said.

Contact: Jerry Jones (615) 322-4747, (615) 322-4747

GoogleNews.com, January 7, 2010  –  It’s the ultimate goal in the treatment of cancer: tailoring a person’s therapy based on his or her genetic makeup. While a lofty goal, scientists are steadily moving forward, rapidly exploiting new technologies. Researchers at Georgetown Lombardi Comprehensive Cancer Center report a significant advance in this field of research using a new chip that looks for hundreds of mutations in dozen of genes.

The goal of personalized medicine is to determine the best treatment and the optimal dose carrying the fewest side-effect, especially as new drugs are discovered and treatment options increase. Variations in our genes encode proteins, which impact how a drug is metabolized or taken in by the cells. This directly impacts the drug’s effectiveness and the kinds of side-effects that may be caused by its toxicity.

“Currently, available genotyping tools test only a few genes at a time,” explains John F. Deeken, a pharmacogentic researcher at Lombardi. “With a new chip called DMET, as many as 170 genes can be examined for more than a thousand variations. This type of turn-key testing, if validated, could eventually replace highly-specialized, time-consuming and labor-intensive testing — thus allowing more institutes the opportunity to pursue genotyping and pharmocogenetic research. That alone would be a significant development for our field and for expediting the research many of us believe is the future of medicine.”

Such a development is particularly critical for cancer research, both in terms of drug discovery and treatment. Genetic variability among patients in cancer clinical trials is not commonly taken into account, a factor that could skew dosage amounts and doom an otherwise promising new drug. A more simple and faster test could be readily incorporated into treatment trials.

In his paper published online December 29 in The Pharmacogenomics Journal, Deeken and colleagues report results of the new genotyping platform called DMET, or drug-metabolizing enzymes and transporters, (Affymetrix, Inc., Santa Clara, Calif.). The DMET “casts a wider net,” screening for 1256 genetic variations in 170 genes involved in drug absorption, distribution, metabolism and excretion.

Deeken says one of the main obstacles facing pharmocogenetic researchers like himself is the lack of a proven and relatively quick technology for genotyping. “DMET appears to offer great promise in this field as a reliable test unveiling genetic variations that correlated with drug effectiveness and toxicity,” says Deeken. “Still, DMET isn’t yet ready for primetime in terms of having received FDA approval, but we’re getting closer.”

Deeken serves as a consultant to Sanofi-Aventis, the manufacturer of docetaxel, a drug involved in the current reported study. Three other authors are employees of Affymetrix, the manufacturer of the DMET platform. The study was done in part at the National Cancer Institute and supported by funding from the National Institutes of Health.

Story Source: Adapted from materials provided by Georgetown University Medical Center,

GoogleNews.com, The New York Times, January 7, 2010  — The Environmental Protection Agency on Thursday proposed stricter health standards for smog, replacing a Bush-era limit that ran counter to scientific recommendations.

The new limits — which are presented as a range — will likely put hundreds more counties nationwide in violation, a designation that will require them to find additional ways to clamp down on pollution or face government sanctions, most likely the loss of federal highway dollars.

The tighter standards will cost tens of billions of dollars to implement, but will ultimately save billions in avoided emergency room visits, premature deaths, and missed work and school days, the EPA said.

The proposed range was what scientists had recommended during the Bush administration. However, former President George W. Bush personally intervened and set the standard above what was advised after protests from electric utilities and other industries. The Bush standard was still stricter than the previous smog standard set in 1997.

EPA Administrator Lisa Jackson said in a statement Thursday that science, this time around, had been followed.

”EPA is stepping up to protect Americans from one of the most persistent and widespread pollutants we face,” Jackson said. ”Using the best science to strengthen these standards is long overdue action that will help millions of Americans breathe easier and live healthier.”

The Obama administration last year had indicated it planned to scrap the Bush smog limits, when it asked a federal judge to stay a lawsuit challenging the March 2008 standards brought by 11 states and environmental groups.

Smog is a respiratory irritant that has been linked to asthma attacks and other respiratory illnesses. It is formed when emissions from burning gasoline, power and chemical plants, refineries and other factories mix in sunlight.

While smog has been a long-term problem in parts of Texas, California, and along the northeast Coast, the new standards could affect counties in Idaho, Nevada, Oregon, the Dakotas, Kansas, Minnesota and Iowa for the first time based on EPA data.

Environmentalists immediately endorsed the decision. ”If EPA follows through, it will mean significantly cleaner air and better health protection,” said Frank O’Donnell, president of the advocacy group Clean Air Watch.

Representatives of the oil and gas industry, which said they have already invested $175 billion toward environmental improvements, were quick to say the proposal lacked ”scientific justification.”

”There is absolutely no basis for EPA to propose changing the ozone standards promulgated by the EPA Administrator in 2008,” the American Petroleum Institute said in a statement. ”To do so is an obvious politicization of the air quality standard setting process that could mean unnecessary energy cost increases, job losses and less domestic oil and natural gas development and energy security.”

The EPA proposal presents a range for the allowable concentration of ground-level ozone, the main ingredient in smog, from 60 parts per billion to 70 parts per billion. That’s equivalent to 60 to 70 tennis balls in an Olympic-sized swimming pool full of a billion tennis balls. EPA will select a specific figure within that range later this year.

The Bush standard adopted in 2008 was 75 parts per billion. Since 1997, it had been 84 parts per billion.

The stricter limit comes with additional costs, from $19 billion up to $90 billion a year by 2020, according to EPA. The Bush administration had put the cost to industry and drivers to meet its standard at between $7.6 billion to $8.5 billion a year.

Counties and states will have up to 20 years to meet the new limits, depending on how severely they are out of compliance. They will have to submit plans for meeting the new limits by end of 2013 or early 2014.


On the Net:

Environmental Protection Agency: www.epa.gov

Research in salamanders is lighting the way to human limb regeneration, scientists say


GoogleNews.com, Jan. 6 (HealthDay News), by E.J. Mundell  —  Each year, thousands of Americans lose fingers, hands or entire limbs in terrible accidents. Prosthetics can help amputees regain some function, and successful hand transplants have recently been achieved.

But wouldn’t it be great if humans could simply regrow missing parts on their own?

Within the space of a generation, this seemingly superhuman power might become a reality, scientists say, and people may have a lowly amphibian to thank for it.

Among the world’s varied creatures, a Mexican salamander called the axolotl appears best at regrowing whole limbs lost to injury. And researchers are hot on the trail of finding out what the axolotl has that humans don’t.

“The crux of what we are doing with this work is to be able to understand the basic biology of regeneration, and then translate that to regenerative therapies,” said one pioneer in the field, biologist David Stocum, director of the Center for Regenerative Biology and Medicine at Indiana University in Bloomington.

His team got a little closer recently, reporting on a key piece of the axolotl regeneration puzzle in the journal BioMed Central Biology.

Stocum’s group found that a cellular protein called EVI5 appears to give cells at the wound site time to regroup and specialize, so they can produce the varied tissue types needed to regrow an amputated limb.

As Stocum points out, humans do have a very limited capacity to regrow complex tissue — namely the fingertip.

That’s no small feat in itself. “The fingertip has got bone, there’s also tendon there, and nerve tissue,” Stocum said. “And the nail is a modification of the skin epidermis. [The fingertip] is pretty complex tissue.”

Still, that’s as far as it goes for regeneration in mature humans. Other animals can regrow complex segments of themselves (many fish regrow lost fins, for example) and the common frog has potent regenerative powers as a tadpole but loses them mysteriously as it matures.

Stocum’s work with both the axolotl and the frog have turned up interesting clues to regeneration. In the salamander, the site of amputation does not close over with scar tissue as it does in most other animals. Instead, a bump of cells called a blastema forms at the injured area.

The cells that collect in the blastema don’t just go in one direction, forming scar tissue. Instead, they huddle and undergo a process called “de-differentiation,” whereby each cell becomes oriented towards a particular disparate tissue type needed to replace the salamander limb — bone, muscle, nerves. This process relies on a complex chain of interconnected biochemical signals, most of which remain mysterious, Stocum said.

But one key player has now emerged: the EVI5 protein, which appears to put the brakes on blastema cell division until proper cell de-differentiation is complete. In essence, Stocum said, high levels of EVI5 tell the wound area to “wait until you have made a little pile of blastema cells before you start dividing.”

There’s no guarantee that a similar system would work in humans, however. For one thing, “it’s pretty well known that fingertip regeneration does not take place by the formation of a blastema like it does in a salamander,” Stocum pointed out. As for the salamander, many more ingredients in the regeneration cocktail still need to be figured out.

Right now, Stocum’s team is busy comparing regenerative processes in the axolotl to those found in the tadpole but not in the mature frog.

“That will give us a handle, we hope, on why the frog loses the power of regeneration” and the axolotl does not, he said.

Another expert agreed that the journey to helping humans regrow lost body parts is just beginning.

According to Dr. Stephen Badylak, a close look at the axolotl is crucial, because “we need to identify what [the human] deficiencies are and then say, ‘Is it possible for us to do something like that or not? Do we even have it in our genome?'”

Badylak, incoming president of the Tissue Engineering and Regenerative Medicine International Society and director of tissue engineering at the University of Pittsburgh’s McGowan Institute for Regenerative Medicine, is optimistic that the regeneration of human fingers or limbs “is possible.” But he added, it may be decades before that happens. In the meantime, regenerative medicine should make smaller but still valuable medical gains, he said.

For example, Badylak’s group is now working with the U.S. Department of Defense to develop better, scar-free wound healing for soldiers. And he believes that scientists are well on their way to regrowing body parts with simpler structures, such as heart muscle or organs such as the kidney.

“We’ll figure out that stuff before the really complex stuff,” Badylak said. “A finger, an arm, a hand — those are extraordinarily complex body parts.”

Stocum agreed that smaller discoveries will inevitably precede larger ones. In the meantime, he said, bioengineers are creating better and more sensitive prosthetics for today’s amputees — devices that would have been unimaginable even a few years ago.

Still, Stocum admitted, “nothing does beat the real thing.”

More information

There’s more on the science of regenerative medicine at the Indiana University Center for Regenerative Biology and Medicine.

SOURCES: David Stocum, Ph.D., professor, department of biology, and director, Center for Regenerative Biology and Medicine, Indiana University, Bloomington; Stephen Badylak, D.V.M., Ph.D., M.D., research professor, department of surgery, director, tissue engineering, McGowan Institute for Regenerative Medicine, University of Pittsburgh, and incoming president, Tissue Engineering and Regenerative Medicine International Society; Nov. 30, 2009, BioMed Central Biology, online

ScienceDaily.com, January 7, 2010  –  Individually designed music therapy may help reduce noise levels in people suffering from tinnitus, or ear ringing, German scientists said earlier this week.

The researchers designed musical treatments adapted to the musical tastes of patients with ear-ringing and then stripped out sound frequencies that matched the individual’s tinnitus frequency.

After a year of listening to these “notched” musical therapies, patients reported a distinct decrease in the loudness of ringing compared with those who had listened to non-tailored placebo music, the researchers wrote in a study published in the Proceedings of the National Academy of Sciences journal.

Tinnitus is a common hearing problem in industrialized countries and the ear-ringing can be loud enough to harm quality of life in between one and three percent of the general population, the researchers said.

A European Union (EU) health panel raised the alarm in January about the potential hearing damage caused by young people playing their MP3 players too loud.

The EU Scientific Committee on Emerging and Newly Identified Health Risks warned that listening to personal music devices at high volume for long periods could cause hearing loss and tinnitus, and their warning prompted the European Commission to issue new safe volume standards for MP3 players.

The German researchers said the precise cause of tinnitus is not known, but the auditory cortex — the region of the brain that processes sound — is often distorted in those who have it.

Christo Pantev of the Institute for Biomagnetism and Biosignalanalysis at Westfalian Wilhelms-University, Germany, who led the study, said his findings on targeted listening suggested that tinnitus volume could be “significantly diminished by an enjoyable, low-cost, custom tailored notched music treatment.”

Henry Ford Health System  –  It’s a ringing, a buzzing, a hissing or a clicking – and the patient is the only one who can hear it.

Complicating matters, physicians can rarely pinpoint the source of tinnitus, a chronic ringing of the head or ears that can be as quiet as a whisper or as loud as a jackhammer.

Now a Henry Ford Hospital study finds that a non-invasive imaging technique can actually aid in the diagnosis of tinnitus and may detect a reduction in symptoms after different treatments, offering hope to the more than 50 million patients with tinnitus.

“Until now, we had no way of pinpointing the specific location of tinnitus in the brain,” says study co-author Michael D. Seidman, M.D., F.A.C.S., director of the Division of Otologic/Neurotolgic Surgery in the Department of Otolaryngology-Head & Neck Surgery at Henry Ford Hospital.

This imaging technique, magnetoencephalography (MEG), can determine the site of perception of tinnitus in the brain, which could in turn allow physicians to target the area with electrical or chemical therapies to lessen symptoms, according to study results being presented Saturday, Oct. 3 at the American Academy of Otolaryngology-Head & Neck Surgery Foundation Annual Meeting & OTO EXPO.

“Since MEG can detect brain activity occurring at each instant in time, we are able to detect brain activity involved in the network or flow of information across the brain over a 10-minute time interval,” explains co-author Susan M. Bowyer, Ph.D. bioscientific senior researcher, Department of Neurology at Henry Ford Hospital. “Using MEG, we can actually see the areas in the brain that are generating the patient’s tinnitus, which allows us to target it and treat it.

Imaging techniques currently used to study tinnitus in the brain – PET and fMRI – provide a general location but are not successful at determining the specific site in the brain that is generating tinnitus symptoms.

MEG, by comparison, measures the very small magnetic fields generated by intracellular electrical currents in the neurons of the brain. Only 20 sites in the U.S., including Henry Ford, are equipped with a MEG scanner. MEG is presently used at these sites for pre-surgical brain mapping for patients undergoing surgery for brain tumor removal or Epilepsy treatment.

“With PET and fMRI, most of the auditory cortex of the brain lights up with activity during imaging. MEG, however, is a much more sophisticated machine and it can identify a specific tone or topic point, so only a small area in the brain lights up. It’s like having the lights on in only the city of Detroit, compared to having the lights on in the entire state of Michigan,” explains Dr. Seidman, director of the Otolaryngology Research Laboratory and co-director of the Tinnitus Center at Henry Ford.

For the study, Dr. Seidman and his colleagues collected MEG results from 17 patients with tinnitus and 10 patients without tinnitus. MEG data were collected for 10 minutes, and then digitally filtered. Study participants wore ear plugs to eliminate outside sounds, and kept their eyes open and fixated on one point on the ceiling in the room during testing.

With tinnitus patients who have ringing in one ear (unilateral tinnitus), MEG imaging detected the greatest amount of activity in the auditory cortex on the opposite site of the brain from their perceived tinnitus. For patients with ringing in the head or both ears (bilateral tinnitus), MEG imaging revealed activity in both hemispheres of the brain, with greater activity appearing in the opposite side of the brain of the strongest perception of tinnitus.

Patients without tinnitus had multiple small active areas in the brain, but no particular areas were found to be highly coherent during the 10-minute MEG scan.

Ultimately, Dr. Seidman says the study establishes MEG as an effective clinical tool for localizing the probably source of tinnitus in patients’ brains. It also has the potential to assist with the development of future interventional strategies to alleviate tinnitus.

About Tinnitus

The American Tinnitus Association estimates that more than 50 million Americans experience tinnitus to some degree; about 12 million have severe enough tinnitus to seek medical attention; and about two million patients are so seriously debilitated that they cannot function on a day-to-day basis.

The exact physiological cause or causes of tinnitus are not known. There are, however, several likely sources, all of which are known to trigger or worsen tinnitus, including exposure to loud noises, wax build-up in the ear, ear or sinus infections, head and neck trauma, and certain disorders, such as hypo- or hyperthyroidism, Lyme disease, fibromyalgia, and thoracic outlet syndrome can have tinnitus as a symptom.

Although there is no known cure for tinnitus, Henry Ford offers several options for coping with the condition, including hearing aids, sound generators and medication, and all come with ongoing counseling. The goal is to provide patients with relief from their tinnitus and a better quality of life.

Journal of Clinical Nursing  –  As many as one in seven people will experience tinnitus, or ringing in their ears, at some time of their life, but not enough is being done to support patients who experience this distressing condition, according to an extensive research review in the November 2009 issue of the Journal of Clinical Nursing.

Tinnitus is the most common injury arising from the conflicts in Afghanistan and Iraq and 75% of 18 to 30 year-olds who go to nightclubs and concerts may experience temporary tinnitus.

“Despite the fact that it is a very distressing condition and can affect people’s lifestyle and quality of life, around 94% of patients are simply told that nothing can be done to alleviate the condition” says Professor Susan Holmes from Canterbury Christ Church University, Kent, UK.

“Tinnitus is a widespread condition that affects millions of people across the world and there is considerable debate about its causes. The condition, which can be permanent or temporary and acute or chronic, increases with age and can also occur after bereavement or during stressful periods.

“It is sometimes referred to as a ‘phantom sensation’ as the sound — often a high-pitched noise with mechanical, electrical or musical qualities — is experienced in the absence of external stimuli.”

Professor Holmes teamed up with Dr. Nigel Padgham, an ear nose and throat surgery specialist from Kent and Canterbury Hospital, to carry out an extensive research review of nearly 150 papers published since 1983.

This showed that although considerable research has been carried out on the subject, nurses — who are often the first people that patients turn to — have received very little guidance or information on the condition.

“We believe that affected patients need considerable support and advice on healthcare options, encouragement to try different treatments and recognition that help and hope are available” says Professor Holmes.

“Though patients may have to learn to live with tinnitus, the most important thing is that they recognize that help is available.”

Other key findings of the research review include:

  • Ten to 15% of people experience tinnitus at some time in their life. Five per cent of the UK’s 4.7 million sufferers experience severe and persistent tinnitus that affects their lifestyle. 19% of Americans have the condition — with only 12 million seeking help. 14.5% of Italians have prolonged spontaneous tinnitus and 1.5 million German adults experience ‘considerably annoying tinnitus’.
  • Tinnitus increases with age and hearing impairment and 85% of patients also have hearing loss. Only 1% of people under 45 get tinnitus, compared with 12% between 60 and 69 and 25% to 30% over 70. Women appear to experience more complex tinnitus, but the reasons are unclear.
  • It is unlikely that tinnitus has a single underlying cause. Many cases relate to ageing and hearing loss, but other causes appear to be damage to the middle ear, cochlea and audiovestibular nerve and cerebral pathways between the cochlear nucleus and primary auditory cortex.
  • Temporary or permanent tinnitus may be due to ototoxic medications, such as certain antibiotics and antimalarial drugs, cancer chemotherapy drugs, non-steroidal anti-inflammatory agents and diuretics.
  • In most cases the onset is gradual and not attributable to any specific event. It can arise in the absence of any hearing problems.
  • Various studies show that 62% of tinnitus sufferers have a “lifetime prevalence of major depression,” 63% display “defined psychiatric disturbance” and 62% have “signs of lifetime depression”.

“While there is debate about what causes tinnitus, it is acknowledged that both acute and chronic tinnitus can be distressing and, for some, persistent tinnitus affects their lifestyle and quality of life” says Dr. Padgham.

“Although there has been a significant amount of research on tinnitus, most of this has focused on developing a better understanding of the cause and therapy rather than on its impact on patients or ways of helping them to cope with the condition.

“Most patients are told that nothing can be done, making them feel hopeless and enhancing the effect the condition has on them.

“But steps can be taken to treat or alleviate tinnitus in many cases, including medication, surgery, hearing aids to amplify external sounds and mask the tinnitus or distraction techniques, such as TV and radio. Healthcare professionals also need to tackle the psychosocial distress caused by the condition, which can include tension, frustration, anger, loss of concentration and sleep disturbance.”

The researchers believe that nurses and other healthcare professionals can play a key role in making patients aware of the fact that help is available and providing them with the support they need to live with their condition.

“Telling patients that nothing can be done is not acceptable” concludes Dr Padgham. “Providing nurses and other health professionals with more information on the condition, and how to manage it, is the first step in that process.”

The Mayo Clinic  –  Ringing, whining, whistling, hissing or whooshing. Any of those sounds in one or both ears when there is no external noise present could be a sign of tinnitus.

The February 2009 issue of Mayo Clinic Women’s HealthSource provides an overview of this common condition. It’s estimated that 10 percent to 15 percent of adults have prolonged tinnitus that often requires medical evaluation. This form of the problem can interfere with sleep, concentration and daily activities.

Tinnitus — pronounced as either TIN-i-tus or ti-NIGHT-us, often is caused by age-related hearing loss. Exposure to loud noises also can damage hearing and lead to tinnitus. Tinnitus can be caused by something as simple as a buildup of wax blocking the ear canal. Some medications, certain antibiotics and cancer drugs can cause or worsen tinnitus. Aspirin — taken in excessive amounts — can cause temporary ringing in the ears, too.

The treatment depends on the root cause. But so far, there is no cure. A medication change or removal of earwax may diminish symptoms for some people.

“One of the frustrating things about tinnitus is that there aren’t any universal successful treatments,” says Charles Beatty, M.D., a Mayo Clinic specialist in head and neck disorders. “The good news is that the problem usually isn’t associated with a serious medical condition, and there are ways we can try to make the tinnitus less annoying and disruptive.”

Treatment strategies that may be beneficial include:

  1. Amplifying hearing with a hearing aid. This may help because the brain would rather process external sounds than be distracted by an internal noise.
  2. Avoiding excessive noise. Ear plugs can be helpful when operating noisy machines.
  3. Avoiding stimulants. Caffeine, nicotine and decongestants can aggravate tinnitus.
  4. Adding background noise. Turning on quiet music, a fan or other background noises can distract the brain from the internal noise.
  5. Using behavioral therapy. Relaxation techniques can help people cope with tinnitus or keep it controlled.
  6. Using medications. Sedatives or antidepressants can help when the condition interferes with sleep or causes a high level of anxiety or stress.

Northwestern University  –  Ernest Moore, an audiologist and cell biologist at Northwestern University, developed tinnitus — a chronic ringing and whooshing sound in his ears — twenty years ago after serving in the U.S. Army reserves medical corps. His hearing was damaged by the crack of too many M16 rifles and artillery explosions. He suspects his hearing also suffered from hunting opossum with rifles as a kid on his grandmother’s farm in Tennessee.

Ever since his ears began ringing, Moore has been researching a cure. He’s at the forefront of just a small band of such scientists in the country. There’s a lot riding on his work.

Half of the soldiers returning from Iraq and Afghanistan exposed to explosive devices suffer from tinnitus. The major cause is exposure to loud noises, which can damage and destroy hair cells of the inner ear. It’s the number one war-related disability.

Nearly 400,000 troops collected disability for service-related tinnitus in 2006, which cost $539 million in 2006. The number climbs nearly 20 percent each year. It could hit $1 billion by 2011, according to the American Tinnitus Association.

An additional 12 million Americans have tinnitus severe enough to seek medical attention. In about two million of those cases, patients are so debilitated they can’t function normally.

Despite the widespread suffering, there has only been a paltry $3 million allotted for public and private research. As a tinnitus researcher, Moore feels like a cross between Rodney Dangerfield and Sisyphus.

It’s been tough to snare research money from the small purse and hard to garner respect for tinnitus. “Ears don’t bleed from tinnitus,” Moore explained. “It’s a hidden problem. It’s not obvious and dramatic like a heart attack or cancer — although it torments its sufferers.” Only one out of ten grant proposals he submits each year have been funded.

The research itself is challenging because Moore can’t ask mice and rats if their ears are ringing. Now, he’s working with zebrafish (yes, they do have ears, which are remarkably similar to humans’ ears.) He’s been able to cause ringing in their ears — he thinks — by exposing them to certain drugs and tracking their erratic swimming on video. Moore then looks at the cells in their ears to see if the electrical firing has increased, an early sign of damage and tinnitus. His early findings show an increased firing.

Then Moore attempts to block this effect with drugs to return the cells to their normal activity. In preliminary research, it appears the drugs he has tested, do slow down the increased electrical firing or tinnitus-like behavior of the hair cells in the ear.

Moore is beginning to meet with doctors to discuss launching a clinical trial to test these drugs for patients with tinnitus.

“If these drugs are found to be safe — and some are already on the market for other uses — and if they are found to have efficacy in humans, then they might be used to treat an individual’s tinnitus,” Moore said.

“If the hair cell is not totally damaged — just beginning to break down, and you administer these drugs, you might be able to prevent it from further damage and interfere with the cells’ ability to generate tinnitus,” he explained.

Tinnitus finally will begin to get some respect when The Department of Defense  Appropriations Bill will open up $50 million in new research funding for tinnitus related to service in the armed forces. Ernest Moore has applied to launch the clinical trial with the drugs he has used with the zebrafish.

By Gabe Mirkin MD, January 14, 2010  —  There are two major types of arthritis: osteoarthritis, also called degenerative arthritis, and reactive arthritis. Osteoarthritis means that cartilage wears away and doctors don’t have the foggiest idea why and therefore they have no effective treatment. Doctors usually prescribe non-steroidal pills that help to block pain but do not even slow down destruction of cartilage. Most serious scientists agree that an infection initiates the reactive arthritises and many think that the germ is often still there when symptoms start. Short-term antibiotics are ineffective, but if antibiotics are started before the joint is destroyed, they can prevent joint damage.

You are more likely to suffer reactive arthritis when you have:
I) positive blood tests for arthritis; all tests used to diagnose arthritis are measures of an overactive immunity;
II) swelling of the knuckles and middle joints of your fingers, causing them to look like cigars;
III) a history of a long-standing infection such as a chronic cough, burning on urination or pain when the bladder is full, chronic diarrhea and belching and burning in the stomach; and
IV) pain that starts at an age younger than 50.

Most rheumatologists refuse to treat their rheumatoid arthritis patients with antibiotics even though several controlled prospective studies show that minocycline drops the rheumatoid factor towards zero and helps to alleviate the pain and destruction of rheumatoid arthritis. The studies, referenced below, include: 1) First Netherlands study, 10 patients, J of Rheumatology 1990;17(1):43-46. 2) 2nd Netherlands Study, 80 patients, Arthritis and Rheumatism 1994;37(5):629-636. 3) Israel Study, 18 patients, J of Rheumatology 1992;19(10):1502-1504. 4) U.S.Mira Study, 219 patients, Annals of Internal Medicine. 1995(Jan15);122(2):81-89. 5) U.S. U of Nebraska Study, 40 patients, Arthritis and Rheumatism 1997;40(5):842-848.

I treat my reactive arthritis patients with Minocycline 100 mg twice a day, (sometimes azithromycin 500 mg twice a week), but this must still be considered experimental because most doctors are not yet ready to accept antibiotics as a treatment. There is also possibility of a rare serious side effect of lupus. Many patients do not feel better for the first few weeks after they start taking minocycline. If a patient does nor feel better after taking 100 mg of minocycline twice day for 2 months, I add Zithromax 500 mg twice a week. If the patient does not feel better after taking the two antibiotics for 6 months, I do add the immune suppressants that most rheumatologists prescribe. But as soon as they feel better, I stop the immune supppressants and continue the antibiotics.

Other papers show that even osteoarthritis may respond to antibiotics (27). People who have chlamydia in their joints usually have no antibodies to that germ in their bloodstream and therefore cannot cure it (30). Reactive arthritis is characterized by pain in many muscles and joints and is thought to be caused by a person’s own antibodies and cells attacking and destroying cartilage in joints. This type of arthritis may be triggered by infection and antibiotics may help to prevent and treat this joint destruction (1 to 10). Short-term antibiotics are ineffective (5). Doxycycline may prevent joint destruction by stabilizing cartilage (3) in addition to clearing the germ from the body.

How do germs cause arthritis? When a germ gets into your body, you manufacture cells and proteins called antibodies that attach to and kill that germ. Sometimes, the germ has a surface protein that is similar to the surface protein on your cells. Then, not only do the antibodies and cells attach to and kill the germ, they also attach to and kill your own cells that have the same surface membranes. Some people with arthritis have high antibody titre to E. Coli, a bacteria that lives normally in everyone’s intestines (15). It has the same surface protein as many cells in your body (15). Normal intestines do not permit E. Coli to get into your bloodstream. Some people who get reactive arthritis may have intestines that allow E. coli to pass into the bloodstream and cause the immune reaction that destroys muscles and joints. The same type of reaction applies to several other bacteria and viruses that can pass into your bloodstream (15A). Venereal diseases, such as gonorrhea, chlamydia and ureaplasma have been found in the joint fluids of many people with arthritis (16). People with reactive arthritis are more likely to have staph aureus in their noses (17) and carry higher antibody titer against that germ (18). Many people with reactive arthritis have had chronic lung infections, caused by mycoplasma and chlamydia, prior to getting joint pains(20,21). Mycoplasma has been found in joint fluid of people with arthritis (28,29). The treatment of arthritis with antibiotics is controversial and not accepted by many doctors; discuss this with your doctor.

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