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Defense mechanism: Researchers creating a new vaccine against H1N1 hope to harness the power of the immune system’s dendritic cells (one such cell is shown above in blue), which are responsible for directing the body’s immune response.
Credit: Oliver Schwartz, Institute Pasteur / Science Photo Library 

 

Researchers are working to treat pandemic flu by recruiting a patient’s own immune cells.

 

MIT Technology Review, December 1, 2009, by Lauren Gravitz  —  Viruses multiply incredibly quickly once they’ve infected their victim–so fast that antiviral medications such as Tamiflu are only effective if given during the first few days of an infection. After that, the viral load is just too high for a single drug to fight off. But researchers are working on a treatment for the H1N1 virus (or swine flu) that uses a different approach. Rather than disabling the virus with a drug, they’re creating a vaccine that can activate and steer a patient’s own immune cells to attack the invader.

Scientists at the Vienna, VA-based Cel-Sci have created a screening platform, called LEAPS (Ligand Epitope Antigen Presentation System) that identifies epitopes–small pieces of a virus that can be used to elicit very specific immune reactions. The DNA segments that make up these epitopes are so short–just eight to 30 amino acids long–that they can be re-created in the lab. Then the Cel-Sci researchers take those segments and attach them to another small molecule–an immune-cell-binding ligand that guides the complex straight to the immune cells in charge of initiating and directing an immune reaction.

The ligand-bound epitope is guided directly to immature dendritic cells, so named for tiny tentacles that reach out in every direction from the main cell body. Dendritic cells are the immune system’s conductors, responsible for initiating and guiding the fight against invaders like the influenza virus. Immature dendritic cells are prompted to mature by the presence of these invaders; the mature dendritic cells then activate T cells, which in turn stimulate very specific immunity against the virus.

“It’s like a live virus vaccine–and more effective–but without the live virus,” says Kenneth Rosenthal, an immunologist at Northeastern Ohio Universities Colleges of Medicine and Pharmacy who has collaborated with the Cel-Sci team.

So far, the company has tested the LEAPS system in mice with herpes and arthritis, and found the approach to be successful in modulating the rodents’ immune responses.

“The LEAPS technology allows you to drive an immune response in a desired direction,” says Cel-Sci director and CEO Geert Kersten. “It’s about modulating an immune response. That’s important, because it’s also possible to rev up the immune system and have no effect whatsoever.”

Now the company is turning its attention to H1N1. In research that has been fast-tracked by the U.S. Food and Drug Administration, Cel-Sci has created a peptide that it believes will direct the human immune system to fight the virus directly. In collaboration with physicians at Johns Hopkins University’s School of Medicine, researchers are collecting blood from 20 patients hospitalized with H1N1, and 20 healthy controls, then stimulating the blood with their peptide to see if they can initiate the appropriate immune responses.

“We need to find the kinds of responses that have commonly been associated with an ultimate positive outcome,” Kersten says. “If we see those kinds of responses, then, based on FDA discussions, we expect to be able to do a randomized clinical trial.” The group hopes to be able to move forward as soon as their results come in.

Kersten is optimistic. “We have a way, at least in other diseases, of directing the cellular immune response without the production of pro-inflammatory cytokines,” he says, referring to signaling molecules that can incite unwanted inflammation. Cytokines are produced by the body’s own immune cells, but when their production goes unchecked and ramps up too high, they can cause the body to overreact to a virus. Cel-Sci’s approach circumvents such a response.

Cel-Sci creates its peptide using epitopes from the small segments of flu virus that don’t mutate, and which could therefore be used to treat H1N1 even as it changes over the course of the year–such an approach could also be effective against other strains of flu, such as avian (H5N1) and even 1918 pandemic influenza.

Using dendritic cells to direct immune response is an attractive mechanism, says Noel Rose, director of the Center for Autoimmune Disease Research at the Johns Hopkins Bloomberg School of Public Health. “This would have applications far beyond H1N1,” he says. “It would be a nice way of having a person make his own vaccine.”

Rose was not involved in the trial, but his lab will analyze the cytokine results. “I have no idea what to expect, because we don’t know what cytokines are going to be produced.” Even so, he says, “I think it could be really interesting.”

There are nearly 1,000 soldiers who have returned from Iraq and Afghanistan with devastating injuries. Now science has a way to regrow body parts.

GoogleNews.com, WNDU.com,November 30, 2009, by Maureen McFadden  —  So far, 5,000 men and women gave their lives while serving in Iraq and Afghanistan. But, there are nearly 1,000 more soldiers who are coming home with devastating injuries.

Amputations, skin grafts and plastic surgeries are the painful battles these wounded warriors face on the home front. Now science has a way to regrow body parts.

Before Afghanistan, U.S. Army Specialist Joseph Paulk looked like the boy next door.

“They found me 20 feet away from the truck engulfed in flames,” says Joseph, who was wounded in Afghanistan. “Forty percent burns to the face, the shoulder, down to my hands.”

When he came home, he learned his battle against the mirror was only beginning. But soon, amputations could be a thing of the past, as doctors grow new body parts.

“We obviously have the potential to create a whole human in nine months,” says Dr. Steve Badylak, Director of the McGowan Institute for Regenerative Medicine in Pittsburgh.

At the University of Pittsburgh, researchers are using powder made from a pig’s bladder to regrow fingers.

In soldiers with more serious injuries, the goal is to at least create fingertips.

“Stimulating the growth of 10 to 11 mm of length allows them to make change at a grocery store, turn the key in the car, hold a fork,” says Dr. Badylak.

Other researchers are working to reconstruct faces damaged by war. Dr. Joseph Vacanti is engineering ears in his lab.

“Ideally, it would be indistinguishable from a normal ear,” says Dr. Vancati, pediatric surgeon at Massachusetts General Hospital for Children at Harvard Medical School.

Already successful in mice, Dr. Vacanti says he plans to implant the first ear on a human within a year.

Dr. Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine, takes a piece of skin from a soldier and cooks it in an oven-like device. Racks stretch the skin until it covers the size of the wound.

“This is basically the same conditions as our body in a box,” says Dr. Atala. “This piece will actually get to be an 8 by 10 piece of skin.”

From civilians out of options, to soldiers whose sacrifice is measured in scars.

“You don’t want to be looked at for your loss,” says Scott Blaine, who was also wounded in Afghanistan. “You want to be just like any other person around.”

Science is growing new possibilities for healing the body and the human spirit.

The Department of Defense is providing Wake Forest, the University of Pittsburgh, Rutgers University and the Cleveland Clinic $85-million over the next five years to perfect organ and tissue-growing techniques.

Experts explain the pros and cons of coronary calcium scores, carotid artery ultrasound, and CT heart scans.

By Charlene Laino
WebMD.com

Reviewed by Louise Chang, MD

 

We’ve all heard the stories: someone seemingly healthy, with normal cholesterol levels and no obvious risk factors, drops dead of a heart attack. How can this happen? 

Morteza Naghavi, MD, says it’s because traditional risk factors may not tell you what you really need to know: whether your arteries are diseased.

“Why are cholesterol, smoking, family history so lousy? Because they’re just risk factors,” says Naghavi, chairman of the Society for Heart Attack Prevention and Eradication (SHAPE) and director of American Heart Technologies in Houston. 

“They don’t speak to whether the arteries are diseased. So we need to directly visualize the artery. Is there plaque and is the artery dilating properly? You can have a diseased artery regardless of how may risk factors you have.”

That disconnect has led more doctors to recommend that patients undergo high-tech heart tests that offer detailed images of the blood vessels as a means of lowering heart disease risks. The three tests — calcium coronary scores, carotid artery ultrasound, and CT heart scans (CT angiography) — “are all good at determining early atherosclerosis, or hardening of the arteries,” says American Heart Association (AHA) past president Robert Bonow, MD, head of cardiology at Northwestern University’s Feinberg School of Medicine in Chicago. “They can help to identify people early on that need aggressive risk factor modification.” 

But as with anything, these tests have their merits and drawbacks. So how can you tell if these tests are for you? To find out, WebMD spoke with three leading heart health experts: Naghavi, Bonow, and Todd C. Villines, MD, co-director of cardiac CT at Walter Reed Army Medical Center in Washington, D.C.

 

1.   Coronary Calcium Scores 

What Are Coronary Calcium Scores?

Calcium is one component of plaque that can build up inside the coronary arteries that supply oxygen-rich blood to heart muscle. Measuring it can help determine the level of plaque buildup that leads to narrowing of the heart arteries, the hallmark of coronary artery disease. 

During the test, you lie in a hollow CT scanner. X-ray beams create multiple images of the heart; a computer measures the amount and density of calcium deposits in the artery walls and provides a calcium score. The score can range from 0 to more than 400, and any score over 100 is associated with an increased risk of heart disease.

“Studies have consistently shown that the higher your calcium score, the higher your risk of heart attack or other coronary artery disease event,” Villines says. One of the most recent studies, published last year in the New England Journal of Medicine, showed that the coronary calcium score predicted heart events — heart attack, death from coronary heart disease, or chest pain (angina) — among men and women of all races. In that study, people with a coronary calcium score of 101-300 were more than seven times as likely to experience a heart event than someone with no evidence of coronary calcium; people with higher scores were at even greater risk.

 

Who Should Get Coronary Calcium Scores?

People at intermediate risk of heart disease based on traditional risk factors. This includes men over 50 with at least one added risk factor and women over 60 with at least two added risk factors, such as high blood pressure or high cholesterol, according to Villines. In these individuals, the need to commence medications to control these risk factors may not be clear. 

For people at intermediate risk, a high calcium score would likely lead to more aggressive lifestyle changes, such as aspirin therapy, and even high-dose statin drugs to control cholesterol, Bonow says. 

On the other hand, if you’re at high risk to begin with (because you have diabetes or because you have heart or vascular disease), you should already be on aggressive therapy, so measuring the calcium score wouldn’t change anything, Bonow explains. And people at low risk are unlikely to have calcium buildup; even if they do, their overall risk of a cardiac event is usually still low, he says. 

One exception may be low-risk women, Villines says. “Data from the Multi-Ethnic Study of Atherosclerosis trial showed that women at low risk and a high calcium score faced the same risk of heart attack or dying of heart disease as people at high risk. So even though it’s not integrated into the guidelines, I would consider this test in women aged 45 to 65 with at least one risk factor — or even with no risk factors when there is a strong family history. It might change management.” 

Naghavi believes that all men ages 45 to 75 and women ages 55 to 75 should undergo screening with either the coronary calcium scan or carotid artery ultrasound — regardless of whether they have other risk factors. People may have low cholesterol levels or other low risk factors and still have heart problems, he says. “We need to go beyond traditional risk factors.” 

Bonow, Villines, and many other doctors disagree, saying that further study is needed to show that widespread screening will truly help. “Testing everyone would lead to a lot of costs and detection of minor abnormalities that mean nothing but can cause needless anxiety and further testing,” Bonow says.

 

Advantages of Coronary Calcium Scores

Villines notes that the only study directly comparing coronary calcium scores to carotid artery ultrasound showed that calcium scores are better at predicting risk of future heart problems. Adds Bonow, “Of the two tests, coronary calcium is probably the better studied. Calcium in the blood vessels is clearly a marker of atherosclerosis, and it can be quantified.”

“The test is painless and quick,” he adds. 

 

Disadvantages of Coronary Calcium Scores

Because calcium deposition is not the first thing that happens during plaque buildup, “a negative test doesn’t mean you don’t have [any] atherosclerosis,” so a low or absent calcium score may make you feel safe even if you’re at risk, Bonow says. 

 

Furthermore, as we age, the chance that some plaque has deposited is significant and it is common for older individuals to display calcification in their arteries. So a positive test doesn’t necessarily place you at risk: In one study, low amounts of calcium were detected in two-thirds of the participants who did not experience coronary events. The key may be your relative score — how you compare to your peers. You may be at increased risk only if your score is significantly higher than expected based upon your age and gender.

Also, the test does involve some exposure to radiation, although “at very low doses,” Bonow says. A new AHA advisory says CT scans should be used judiciously to minimize exposure to ionizing radiation, but that medically appropriate examinations should not be avoided.

How Much Do Coronary Calcium Scores Cost?

The test typically costs $200 to $500. As with most screening tests, Medicare and other insurers usually do not pick up the tab.

 

2. Carotid Artery Ultrasound 

What Is Carotid Artery Ultrasound?

This test uses ultrasound and sophisticated software to quantify the thickening of the inner walls of the carotid arteries that supply blood to the brain, a sign of early atherosclerosis. “Studies in over 50,000 patients have shown that if you’re in the 75th percentile or higher for your age group, you have a higher risk of coronary heart disease and stroke,” Villines says. Being in the 75th percentile means that 75% of your peers had less artery thickening than you.

 

Who Should Get Carotid Artery Ultrasound?

As with coronary calcium scores, carotid artery ultrasound should be reserved for people at intermediate risk of heart disease based on traditional risk factors, according to Bonow and Villines. Naghavi says SHAPE “recommends carotid artery ultrasound or coronary calcium scores as a first line of screening for men over 45 and women over 55. However, of the two tests, I’d lean toward calcium scores.”

 

Advantages of Carotid Artery Ultrasound

This is a painless noninvasive test that can be performed easily in the doctor’s office and does not expose the patient to radiation.

 

Disadvantages of Carotid Artery Ultrasound

Unlike coronary calcium scores, carotid artery ultrasound “does not inform you directly about the heart,” as you are looking at the arteries in the neck, Naghavi says.

Also, the accuracy of the test is very dependent on the skill and expertise of the technologist performing the study, “so you need a trained operator who knows all the current protocols. Be sure to ask if your institution follows the most current guidelines,” Villines advises. 

 

How Much Does Carotid Artery Ultrasound Cost?

The test typically costs $200 to $500. As with most screening tests, Medicare and other insurers usually do not pick up the tab.

 

3. CT Heart Scans 

What Is a CT Heart Scan?

During CT heart scans (also know as CT angiography), patients receive a contrast dye through an IV. X-rays are passed through the body and are picked up by detectors in the scanner. Special software uses the information gathered during the scan to create 3D images of the coronary arteries on a computer screen.

CT angiography scans give doctors a detailed look at the coronary arteries, which supply blood to heart muscle, without cardiac catheterization.

  

Who Should Get CT Heart Scans?

While contrary calcium scores and carotid artery scans are used to evaluate people without symptoms, CT angiography is typically reserved for intermediate-risk people with symptoms such as chest pain or shortness of breath that could be due to coronary heart disease, Villines says.

CT heart scans can also be useful if a patient is at low risk for heart disease and has “mildly abnormal” results on an exercise stress test. “Right now, these patients are referred for catheterization, but the CT scan could help avoid that,” he says.

  

Advantages of CT Heart Scans

The technique is quick, producing pictures within five to 10 seconds, compared with 30 to 45 minutes for cardiac catheterization, the “gold standard” for evaluating blood vessel obstructions. It’s noninvasive, with less risk and discomfort than catheterization, which often requires sedatives and sometimes a night in the hospital.

  

Disadvantages of CT Heart Scans

It fails to produce good images in people with a lot of calcium deposits in their arteries, Bonow says. It should not be used in people with chronic kidney disease or severely obese patients, Villines says.

There are also concerns about cancer risks. According to a new study, CT angiography has the potential to expose patients to high doses of radiation, and methods available to reduce radiation dose are not frequently used. A recent study reported that the average radiation exposure from a CT angiogram evaluation is equivalent to 600 chest X-rays.

Villines says that over the past two years, Walter Reed doctors have been able to reduce radiation during CT angiography by 50% to 70% through the use of radiation-sparing techniques. Patients should ask if such methods will be used before having the procedure, he advises.

 

How much do CT Heart Scans cost?

The CT scan, including the doctors’ fee, costs about $1,000. Medicare and other insurers are still evaluating whether to pay for the scans.

In summary, there are several tests which can be used to determine whether or not you have diseased arteries. The results of such tests could influence the type of preventive treatments which are recommended. However, no test is perfect and regardless of test results, optimizing lifestyle choices still remains a cornerstone of heart disease prevention.

When it comes to your heart health, there are no hard and fast rules, our experts say. Talk to your doctor if you have any concerns.