Thursday, January 3, 2008

Louis J Sheehan 63495 H18

It’s probably the happiest root canal ever: Molecular archaeologists reported last January that they had drilled into a 10,300-year-old human tooth discovered in Alaska and extracted genetic gold. The molar, recovered from skeletal remains found in 1996 in On Your Knees Cave, located on Prince of Wales Island off southern Alaska, holds the oldest genetic sample ever recovered in the Americas. That sample supports the theory that humans first arrived here about 15,000 years ago and then migrated down the continent’s western coastline.

Brian Kemp, a molecular anthropologist at Washington State University who led the study, found that out of 3,500 Native Americans examined from a genetic database, 1.5 percent showed the same genetic pattern in their mitochondrial DNA as that found in the ancient tooth. “What’s interesting is that the distribution is almost entirely down the west coast of the Americas, all the way down to Tierra del Fuego,” says Kemp. That, says Theodore –Schurr, an anthropologist at the University of Pennsylvania, “lends credence to the reemerging hypothesis that the first modern human populations to arrive in North America and then populate the rest of the Americas used a coastal route to actually get there.”

Kemp also compared the ancient DNA with its related modern DNA to see how fast it mutated over time. This “molecular clock” of mutation rates can be used to calculate when the ancestors of today’s Native Americans first arrived on these shores. Previous estimates pegged their appearance as far back as 40,000 years ago, but Kemp’s newly calibrated clock speeds up the scenario. “Within the last 15,000 years is my bet,” he says.

In the traditional view of photosynthesis, the energy carried by photons streaming from the sun is transferred by bouncing from one chlorophyll molecule to the next, a process that ultimately builds simple carbohydrates from water and carbon dioxide. But last spring, a team led by Graham Fleming, deputy director of the Lawrence Berkeley National Laboratory, reported that the process is much more interesting than that.

Using ultrafast lasers, they found that the interaction between the sun’s energy and the chlorophyll molecules in a bacterium relies on a piece of quantum mechanical weirdness known as superposition, where a single photon’s energy can temporarily be in many different states at once. This allows photosynthesis to probe all the possible reaction pathways within the various chlorophyll molecules. The most efficient pathway is selected and energy is transferred through the bacterium as the superposition collapses.

“This is similar to quantum computing in some sense,” says Greg Engel, a member of Fleming’s team. “This is how quantum computing realizes its incredible efficiency and its ability to solve very complex problems, because it can evaluate many solutions at once.”

It may seem like simple compassion to give the terminally ill access to experimental drugs not yet approved by the FDA, but some argue it may also jeopardize the effectiveness of clinical trials and leave patients open to exploitation. In August, the U.S. Court of Appeals for the District of Columbia upheld (pdf) the power of the FDA to control patients’ access to unapproved drugs. The court stated that patients do not have a fundamental right to drugs that have not been proven safe.

The Abigail Alliance for Better Access to Developmental Drugs and the Washington Legal Foundation had filed the suit against the FDA. “What we argue in our lawsuit is that the decision should be a patient’s with their doctor,” says Frank Burroughs of the Abigail Alliance. He founded the organization in 2001 after his 21-year-old daughter Abigail died from head and neck cancer. She had been denied access to the experimental drug Erbitux, which was later approved by the FDA. Burroughs says the groups are planning an appeal to the U.S. Supreme Court.

Many legal experts and ethicists argue that access to unapproved drugs would undermine the scientific process that determines which drugs are effective as well as the FDA’s ability to determine drug safety. Only 8 percent of cancer drugs that enter clinical trials earn FDA approval. The bulk are rejected as ineffective or unsafe. “The very, very sick are open to exploitation,” says Arthur Caplan, chairman of medical ethics at the University of Pennsylvania. He also notes that patients may not join clinical trials if they can get the drugs otherwise, which could impair the development of new drugs.

“I think the court got it right,” says Peter Jacobson of the –University of Michigan School of Public Health. Jacobson views the FDA’s efforts to extend the compassionate use policy as the better way to handle the issue. “Then you’re able to distribute some of these drugs under some kind of scientific protocol without compromising clinical trials that are needed for long-term –understanding.”

The CDC's vaccine advisory panel voted to make shingles vaccination routine for all Americans 60 and older.

Shingles is a painful disease caused by reactivation of dormant varicella zoster virus, or VZV. Best known as the virus that causes chickenpoxchickenpox, VZV is a herpesherpes virus that can come back with a vengeance when a person's immunity wanes with age, disease, or immunity-suppressing drugs.

Without vaccination, about 20% of people who have had chickenpox eventually will get shingles. A person who lives to be 85 has a 50% chance of getting shingles.

Shingles is a bad enough disease to be a good reason to get vaccinated.

But in about a third of cases, shingles turns into an excruciatingly painful disease called postherpetic neuralgia, or PHN. A smaller percentage will get a painful, blinding disease called ophthalmic zoster.

The new vaccine, Merck's Zostavax, won FDA approval last May.

Now the main U.S. vaccine advisory panel -- the Advisory Committee on Immunization Practices (ACIP) -- officially recommends routine use of the vaccine for everyone 60 and older.

The committee voted not to make shingles vaccination routine for people under 60, citing a lack of clinical data on vaccination in that age group.

Similarly, the panel said there was too little data for it to recommend that doctors offer the vaccine for people about to undergo immunity-suppressing treatments.
Good Vaccine, Terrible Disease

A major clinical trial shows the vaccine is more than 60% effective in reducing shingles symptoms. Perhaps most importantly, it reduces painful PHN by at least two-thirds.

"Reducing PHN is the motivation for most of us working on this clinical trial," Michael N. Oxman, MD, of the University of California, San Diego, said in a presentation to the ACIP. "For people with severe PHN, their lives are blighted and the lives of their families are blighted."

PHN pain can last for years. Sudden, lancing pain can quite literally bring patients to their knees. Each year, there are more suicides due to PHN pain than due to cancercancer pain.

And PHN isn't the only bad complication of shingles. Some 15% of shingles patients get ophthalmic zoster -- shingles that affects one or both eyes.

In a public comment, Herbert Kauffman, MD, former chairman of ophthalmology at Louisiana State University, offered the ACIP a graphic description: "This is not going blind in peace and quiet," Kauffman told the ACIP. "This is an all-consuming pain patients live with every moment of every day for years."

The ACIP recommendation means insurers will be more likely to pay for shingles vaccination in 60-and-over patients.

In one of the first studies to detect cancer using RNA in saliva, researchers were able to differentiate patients with head and neck cancer from healthy subjects based on biomarkers found in their saliva, according to an article in the Dec. 15 issue of the journal Clinical Cancer Research.

Researchers at the University of California Los Angeles’ Jonsson Comprehensive Cancer Center reported in the March 2004 issue of Journal of Dental Research that people have about 3,000 clinically distinct types of RNA in their saliva. This discovery led to a novel clinical approach called salivary transcriptome diagnostics.

In a study to evaluate this diagnostic approach’s value, researchers collected unstimulated saliva from 32 subjects with cancers of the mouth, tongue, larynx and pharynx and 32 matched control subjects. When they extracted RNA from the saliva samples, they discovered that 1,679 genes were expressed at significantly different levels in the test subjects’ saliva than in the control subjects’ saliva.

Study results also showed that a combination of four RNA biomarkers provided a detectable signature for head and neck cancer. Researchers conducted a blinded second saliva screening and identified the signature in test subjects with 91 percent sensitivity and specificity.
Louis J Sheehan
Louis J Sheehan, Esquire
Louis J Sheehan Esquire

"We will follow up with a larger cohort of about 200 patients in the near future," said senior author David Wong, D.M.D., D.M.Sc. "This study will hopefully allow us to distinguish in saliva between the various stages of the cancer and ultimately push our accuracy up to as close to 100 percent as possible."

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