Sunday, May 31, 2009

Are Cancer Drugs Worth The Money?

Matthew Herper and Robert Langreth 05.30.09, 4:15 PM ET

ORLANDO - At the annual meeting of the American Society for Clinical Oncology, giant banners with pictures of heroic cancer patients proclaim doctors are "Personalizing Cancer Care."

But many companies seem to be maximizing cancer profit instead. Big drug companies are making big money off smaller and smaller improvements in cancer care. Newfangled cancer drugs can cost $50,000 a year, and that doesn’t mean they will add a year to the patient’s life--you might spend $50,000 for a year and extend the patient's life by only weeks.

The numbers would look better if drug companies did a better job of targeting drugs at the patients most likely to benefit. But that targeting has occurred in only a few scattered examples.

The skyrocketing costs for limited benefit are leading some experts to worry about whether the medical system has the right incentives.

"We are wasting a lot of resources treating people with treatments they don't need," says Otis Brawley, chief medical officer at the American Cancer Society. Novartis, Wyeth and Pfizer all sell very expensive cancer pills. "We would like to believe that cost should be no object, but that is not reality," says Leonard Saltz, a colon-cancer expert at Memorial Sloan-Kettering Cancer Center.

The poster child for high-cost cancer drugs is Roche's Avastin. The drug has $4.8 billion in sales and is approved to treat breast, colon, lung and brain cancer. It was first approved in 2004 after research showed it could extend survival in advanced colon-cancer patients by five months.

The hope was that further studies of Avastin in other types of cancer or in earlier stages of the disease would show even greater survival benefits. But they haven’t. In several breast-cancer trials--including a new one being presented at the meeting this weekend--Avastin slowed the progression of disease but did not extend patient survival at all. But doctors still use the drug in treating breast cancer because they figure it helps symptoms, even if patients don’t live longer. Avastin costs up to $55,000 a year.

In another major study presented at the meeting, Avastin failed to prevent colon cancer from recurring after surgery. In the first year of treatment, more patients who got Avastin remained free of detectable cancer. But after a year, the drug was stopped, and by the end of the study, the apparent initial benefit had faded completely.

Historically, the goal of therapy in early-stage cancer has been to increase the cure rate. But results hint that Avastin may not be curing anyone--it may suppress microscopic cancer deposits without killing them by preventing the growth of their blood vessels. The doctor who conducted the trial, Norman Wolmark of Allegheny General Hospital, is talking about testing Avastin for twice as long in order to get an effect, but that may not be enough. To make a difference in early-stage disease, "the patient may need very, very long-term or even permanent treatment with Avastin," says Saltz. "It gets phenomenally expensive."

Roche says the hints of efficacy support Avastin's future prospects. "It is a validation of the fact that Avastin has a role in early-stage disease," says William Burns, head of Roche's pharmaceuticals division. He forecasts Avastin could still reach sales of $8 billion by 2012 or 2013, even without use in earlier stages of cancer. "With Herceptin, we have learned that it is a drug to start with and stay with" at multiple stages of disease, says Burns, referring to the company's targeted breast cancer drug. "We are start[ing] to piece together exactly the same journey for Avastin."

Burns says the company will consider altering its ongoing trials of Avastin in early-stage breast and lung cancer to include longer-term Avastin use.

Roche is also combining other expensive drugs with Avastin. One study at the meeting showed that adding Tarceva, from OSI Pharmaceuticals and Roche, delayed by one month the median time it takes lung tumors to grow. While it is not yet possible to tell whether there is an effect on survival, the results were statistically significant and financially momentous. U.S. sales of Tarceva were $457 million last year. "We estimate we have the potential for at least $500 million in new [U.S.] business from this study," says OSI Chief Executive Colin Goddard.

One problem is that doctors have no idea which patients are likely to benefit from Avastin, so they give it to everyone in hopes that a few will benefit. Another strategy might be to amp up the search for blood-test results that could predict whether a patient will respond to Avastin, says Angela DeMichele, an oncologist at the University of Pennsylvania whose research focuses on breast cancer. There are clues as to how patients most likely to benefit from Avastin might be identified, she says, but these avenues haven't been pursued yet. "We're still treating people in an unselected way," DeMichele says.

"Avastin is probably not a targeted therapy, as far as I am concerned," says MD Anderson Cancer Center breast cancer expert Franciso Esteva.

Drugs like Tarceva and AstraZeneca's Iressa, which is no longer used in the U.S., work best in patients whose tumors have a mutation in the gene for the epidermal growth factor receptor (EGFR), which is involved in cell growth. In another lung cancer study, Tarceva only slightly delayed the median progression in the overall group of patients, but the small subset of patients with EGFR mutations in their tumors had a tenfold lower risk of the tumor progressing when they took Tarceva.

Since Iressa, AstraZeneca has made a point of pairing drugs with diagnostic work. But it didn’t with Zactima. This experimental drug delayed the progression of lung cancer by three weeks to 17 weeks. Although promising--and viewed as one of AstraZeneca’s most important new products--it has not been paired with a test. Doctors hope for a greater benefit if it is used in earlier stages of the disease.

One of the most impressive results was not from a fancy new therapy at all. Alimta, a more traditional chemotherapy pill sold by Eli Lilly, didn't just slow tumor progression but also increased survival for patients with non-small-cell lung cancer by a median 2.8 months, extending survival to 13.4 months.

Sanofi's Breast Cancer Bet

Sanofi's Breast Cancer Bet
Robert Langreth and Matthew Herper 05.31.09, 1:50 PM ET

ORLANDO, Fla. -- North Carolina resident Terri M. Allen noticed two strange pimple-like bumps on her scalp in June 2007. When she finally got them checked out, her worst fears were confirmed. Her breast cancer that had been removed in 2005 had returned with a vengeance, spreading to her sternum, hipbone and both lungs. Worse, she had a particularly nasty form called triple negative that doesn't respond to several standard treatments.

"I thought I was not going to make it," says Allen, now 54. Then her doctor told her about an experimental drug from Sanofi-Aventis that is looking promising in patients with her form of cancer. She started taking the drug along with chemo in March 2008. Within three months the tumors had virtually disappeared. "This is incredible to me," says Allen, who remains on the Sanofi drug and in remission. "I have no side effects and a completely normal standard of life."

Allen is among the first to benefit from a new class of drugs that aim at a weak spot in certain breast and ovarian cancers: limitations in their inability to repair DNA damage. While not cures, the drugs, called PARP inhibitors, may work well in triple negative breast cancers, about 15% of cases. They also show promise in patients with cancer due to inherited mutations in the BRCA1 and BRCA2 genes.

PARP inhibitors are among the few hot new drugs being highlighted at an otherwise sleepy meeting of the American Society of Clinical Oncology in Orlando. In a trial on 116 triple negative patients, patients who got the Sanofi parp drug lived 3.5 months longer than those who just got standard cell-killing chemotherapy regimens. "It is a big deal," says study leader Joyce O'Shaughnessy of the Baylor Charles A. Sammons Cancer Center. "We don't see survival advantages very often in [advanced] breast cancer." Adds Eric Winer, a breast cancer expert at the Dana-Farber Cancer Institute: "This is one of the most exciting results we have seen in a long time" for these patients. Triple negative cancers aren't responsive to standard hormone therapy or the drug Herceptin.

Sanofi-Aventis Chief Executive Christopher Viehbacher hopes that the drug will reinvigorate his company's cancer franchise. Sanofi sells some of the world's most used chemotherapy drugs, but has never made a name in the newer targeted drugs that are mainstays for Roche, Eli Lilly and Novartis. The PARP drug could help change this. Sanofi got the drug with its $500 million acquisition of BiPar Sciences, a biotech firm with only 18 employees that Sanofi bought earlier this year.

"This is a first-in-class drug, so it puts us back in the game of really innovative medicine," says Viehbacher. "There are other PARP inhibitors out there, but for the moment we've been able to stay in the lead." Parp stands for poly (ADP-ribose) polymerase.

Sanofi's biggest competition is AstraZeneca. It has tested its drug in an even narrower group of patients, women with inherited mutations in the BRCA1 or BRCA2 genes. (About 5% of breast cancer patients, including Allen, have one of these mutations.) Two small studies at the meeting found that the AstraZeneca's drug helped shrink 41% of breast cancer patients with the mutations and also helped ovarian cancer patients, without the need for chemotherapy.

One patient it helped is 70-year-old Los Angeles resident Barbara Shellow. She started on the AstraZeneca PARP inhibitor for her advanced ovarian cancer in July 2007, and her tumors quickly shrank. She has now gone 18 months without a relapse. "The drug has been a miracle for me," she says. Larger trials will be needed to confirm the benefits of both drugs before they can be approved.

If AstraZeneca or Sanofi had tested their drugs on all breast cancer patients, they likely would not have worked, as most breast tumors probably aren't being driven by aberrant DNA repair. "One of the key things is to match the cancer drug to the right patient population," says Alan Ashworth at the Institute of Cancer Research in London, who did an early experiment showing that patients with BRCA mutations might be susceptible to PARP blockers.

Many tumor types besides breast and ovarian may have DNA repair defects. A problem is there is no good test yet to determine which tumors have such defects. Researchers are furiously working to find one, says Ashworth.

"Getting at the molecular defects that are driving cancer is the only way to intelligently apply targeted therapy," says William Audeh, an oncologist at Cedars-Sinai Medical Center in Los Angeles who is testing the AstraZeneca drug. He says researchers need to start treating patients based on what mutations lie hidden inside their tumors, instead of based on what part of the body the tumor is in.

Tuesday, May 26, 2009

Top 5 Cholesterol Myths

Even if you think you know everything there is to know about cholesterol, there may be a few more surprises in store. Check out these common myths about high cholesterol; find out who’s most likely to have it, what types of food can cause it, and why—sometimes—cholesterol isn’t a bad word.


Myth 1: Americans have the highest cholesterol in the world

One of the world’s enduring stereotypes is the fat American with cholesterol-clogged arteries who is a Big Mac or two away from a heart attack. As a nation, we could certainly use some slimming down, but when it comes to cholesterol levels we are solidly middle-of-the-road.

According to 2005 World Health Organization statistics, American men rank 83rd in the world in average total cholesterol, and American women rank 81st; in both cases, the average number is 197 mg/dL, just below the Borderline-High Risk category. That is very respectable compared to the top-ranked countries: In Colombia the average cholesterol among men is a dangerous 244, while the women in Israel, Libya, Norway, and Uruguay are locked in a four-way tie at 232.

Myth 2: Eggs are evil

It’s true that eggs have a lot of dietary cholesterol—upwards of 200 mg, which is more than two-thirds of the American Heart Association’s recommended limit of 300 mg a day. But dietary cholesterol isn’t nearly as dangerous as was once thought. Only some of the cholesterol in food ends up as cholesterol in your bloodstream, and if your dietary cholesterol intake rises, your body compensates by producing less cholesterol of its own.

While you don’t want to overdo it, eating an egg or two a few times a week isn’t dangerous. In fact, eggs are an excellent source of protein and contain unsaturated fat, a so-called good fat.

Myth 3: Kids can’t have high cholesterol

Most people think high cholesterol is a problem that’s strictly for the middle-aged. But guess what? Research has shown that atherosclerosis—the narrowing of the arteries that leads to heart attacks—can start as early as age eight. In July 2008, the American Academy of Pediatrics released guidelines on kids and cholesterol that recommended that children who are overweight, have hypertension, or have a family history of heart disease have their cholesterol tested as young as two years of age.

Children with high cholesterol should be on a diet that restricts saturated fat to 7% of calories and no more than 200 mg per day of dietary cholesterol, according to the guidelines. Fiber supplements and more exercise are also recommended.

While the guidelines prompted a bit of an outcry from parents worried that doctors would be pushing cholesterol-lowering drugs for kids, a new study suggests that less than 1% of adolescents aged 12 to 17 would be considered candidates for medication.

Myth 4: Food is heart-healthy if it says “0 mg cholesterol”

The Cholesterol portion of the nutritional label refers to dietary cholesterol, which is only one of the things found in food that can cause your cholesterol to go sky-high. (A bigger contributor to elevated cholesterol? A high-fat diet.) It’s also believed to be the least important. Saturated fat (found in animal foods and dairy products) and trans fats (found in packaged foods) appear to have a far greater impact on low-density lipoprotein (LDL), the so-called bad cholesterol that causes atherosclerosis, than dietary cholesterol.

Myth 5: Cholesterol is always a bad thing

When most people hear “cholesterol” they think “bad.” Like most things in life, the reality is more complex. High cholesterol can be dangerous, but cholesterol itself is essential to various bodily processes, from insulating nerve cells in the brain to providing structure for cell membranes. That’s why your body makes the white, waxy substance (about 75% of the cholesterol in your blood is made by the liver and cells elsewhere in your body).

The role of cholesterol in heart disease is often misunderstood. Cholesterol is carried through the bloodstream by low-density and high-density lipoproteins (LDL and HDL). LDL, known as bad cholesterol, and not the cholesterol it carries per se, is responsible for atherosclerosis.

Sunday, May 24, 2009

WU engineers develop ultrasound cell phone

William D. Richard (left) takes an ultrasound probe of colleague David Zar's carotid artery with a low-power imaging device he designed.
(David Kilper/WUSTL Photo)
By Liz Stoever

Everyone knows cell phones can pinpoint your location by GPS signals, record photos and video, browse the Internet and keep your schedule. They even can make phone calls.

But now, thanks to engineers at Washington University, cell phones can scan your insides.

Computer engineers David Zar and David Richard have invented a combination ultrasound and high-end smart phone — a super-portable device to scan the body using sound waves.

The new device, adapted from existing portable ultrasounds, will provide a cheaper and more portable alternative to ultrasounds typically limited to hospitals.

In a world where 70 percent of the population does not have access to medical imaging, Zar said, he and his partner expect the device to permanently change the current medical and global computer landscape.

"Twenty-first century medicine is defined by medical imaging," Zar said. "But it's typically not used."
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Although ultrasounds are very practical, they can be difficult to use because the machines are large, old and shared, Zar said. With the cell phone ultrasound, doctors can use it more often.

"This fits in a coat pocket and the whole thing can start up in 10 to 15 seconds," Zar said.

The device also allows patients with diseases such as Duchenne muscular dystrophy to do ultrasounds at home and send information to any centralized unit in the world for a diagnosis.

The device's mobility will also be helpful in developing countries where hospitals are far, but cell phone towers may be more abundant.

Everyone, not just medical professionals, can purchase the ultrasound device from California-based Interson Corp., the manufacturer, in about a month. While ultrasounds are relatively safe, Zar said frequent use can be problematic, and he does not recommend it to pregnant mothers.

Zar and Richard received a $100,000 grant from the Microsoft Corp. in 2008 as part of its larger project to make health care mobile in remote areas. Microsoft External Research has funded approximately $2 million dollars toward projects using cell phones for health care.

About 15 other projects are already under way under the grant program and have produced results including a device that also attaches to a cell phone and can help children with autism communicate more effectively through picture-based communication. Another cell phone compatible device monitors heart rhythms and can diagnose heart problems.

Kristin Tolle, senior research program manager at Microsoft External Research, said the mobile health care project is more prominent than others because it can work anywhere in the world.

"We wanted to encourage ideas," she said. "We are really trying to help underserved communities."

Dr. Antonella Quattromani, a cardiologist on staff with DePaul Health Center, who went on a mission to Ecuador in March, said the device would be very practical on her other mission trips to remote areas.

"The quality of the image is good," she said. "It would be really useful."

The only limitation is the cell phone reception needed to send images in some remote areas, Quattromani said.

By next year, however, everyone in the world should have access to a cell phone tower, Tolle said.

Before the device becomes available to developing countries, Zar said they will need help developing training and distribution for the device.

"This is much bigger than two geeks at Washington University can support," Richard said. "We need layers of people between us and the people on the ground in India."

Friday, May 22, 2009

The Obamacare to Come

The Obamacare to Come
Dems’ health-care plans do not provide the reform most Americans seek.

By Michael Tanner

Drip by painful drip, the details of the Democratic health-care-reform plan have been leaking out. And from what we can see so far, it looks like bad news for American taxpayers, health-care providers, and, most important, patients.

The plan would not initially create a government-run, single-payer system such as those in Canada and Britain. Private insurance would still exist, at least for a time. But it would be reduced to little more than a public utility, operating much like the electric company, with the government regulating every aspect of its operation.

It would be mandated both that employers offer coverage and that individuals buy it. A government-run plan, similar to Medicare, would be set up to compete with private insurers. The government would undertake comparative-effectiveness and cost-effectiveness research, and use the results to impose practice guidelines on providers. Private insurance would face a host of new regulations, including a requirement to insure all applicants and a prohibition on pricing premiums on the basis of risk. Subsidies would be extended to help middle earners purchase insurance. And the government would subsidize and manage the development of a national system of electronic medical records.
The net result would be an unprecedented level of government control over one-sixth of the U.S. economy, and over some of the most important, personal, and private decisions in Americans’ lives.

Let’s look at some of the most troubling ideas in detail.

An employer mandate. Employers would be required to insure their workers through a “pay or play” mandate. Those who did not provide “meaningful coverage” for their workers would pay a penalty, equal to some percentage of their payroll, into a national fund that would provide insurance to uncovered workers. Such a mandate is, of course, simply a disguised tax on employment. As Princeton University professor Uwe Reinhardt, the dean of health-care economists, points out, “[That] the fiscal flows triggered by mandate would not flow directly through the public budgets does not detract from the measure’s status of a bona fide tax.” Estimates suggest that an employer mandate could cost 1.6 million jobs over the first five years.

An individual mandate. As is the case with an employer mandate, an individual mandate is essentially a disguised tax. It is also the first in a series of dominoes that will lead to greater government control of the health-care system.

To implement an insurance mandate, the government will have to define what sort of insurance fulfills it. As the CBO puts it, “an individual mandate . . . would require people to purchase a specific service that would have to be heavily regulated by the federal government.” At the very least, deductible levels and lifetime caps will have to be specified, and a minimum-benefits package will likely be spelled out. This means the oft-repeated promise that “if you are happy with your current insurance, you can keep it” is untrue. Millions of Americans who are currently satisfied with their coverage will have to give it up and purchase the insurance the government wants them to have, even if the new insurance is more expensive or covers benefits the buyer does not want.

A “public option.” The government would establish a new universal-health-care program, similar to Medicare, that would compete with private insurance. Regardless of how it is structured or administered, such a plan would have an inherent advantage in the marketplace because it would ultimately be subsidized by taxpayers. It could, for instance, keep its premiums artificially low or offer extra benefits, then turn to the U.S. Treasury to cover any shortfalls. Consumers would naturally be attracted to the lower-cost, higher-benefit government program.
A government program would also have an advantage because its tremendous market presence would allow it to impose much lower reimbursement rates on doctors and hospitals. Government plans such as Medicare and Medicaid traditionally reimburse providers at rates considerably below those of private insurance. Providers recoup the lost income by raising prices for those with private insurance. It is estimated that privately insured patients pay $89 billion annually in additional insurance costs because of cost-shifting from government programs. If the new public option would have similar reimbursement policies, it would result in additional cost-shifting of as much as $36.4 billion annually. Such cost-shifting would force insurers to raise their premiums, making them even less competitive with the taxpayer-subsidized public plan. Lewin Associates estimates that as many as 118.5 million Americans, nearly two out of every three people with insurance, would shift to the government program. The result would be a death spiral for private insurance.

Given that many of the most outspoken advocates of the “public option” have, in the past, supported a government-run single-payer system, it is reasonable to suspect they support a public option precisely because it would squeeze out private insurance and eventually lead to such a system. President Obama himself has said that if he were designing a health-care system from scratch, his preference would be a single-payer system “managed like Canada’s.” He has also said that, while his proposal is a less radical approach, “it may be that we end up transitioning to such a system.”
Comparative- and cost-effectiveness research. In an attempt to control health-care costs, the government would undertake research to determine which health-care procedures and technologies are most effective and, more ominously, cost-effective. Of course, there is a great deal of waste in the U.S. health-care system, and if the government’s goal were simply to provide better information there would be little cause for concern. But there is every reason to believe such research would be used to impose restrictions on how medicine is practiced. For example, some reform advocates have said that when an insurance company fails to comply with government practice guidelines, workers should no longer be able to exempt the value of that company’s plans from their taxable income.

There is no doubt that other countries use comparative-effectiveness research as the basis for rationing. For example, in Great Britain, the National Institute on Clinical Effectiveness makes such decisions, including a controversial determination that certain cancer drugs are “too expensive.” The U.K. government effectively puts a price tag on each citizen’s life — about $44,305 (£30,000) per year, to be exact, under NICE’s guidelines. That’s just a baseline, of course, and, as NICE chairman Michael Rawlins points out, the agency has sometimes approved treatments costing as much as $70,887 (£48,000) per year of extended life. But such treatments are approved only if it can be shown they extend life by at least three months and are used for illnesses that affect fewer than 7,000 new patients per year.

The final health-care-reform bill is likely to include a number of other bad ideas: a host of new insurance regulations that will drive up costs and limit consumer choice (under one leaked proposal, Americans would be limited to a choice of four standardized insurance plans); subsidies for middle-class families (a family of four earning as much as $83,000 per year would receive subsidized care under one proposal); and government preemption of private investment and research into health IT. All of this would come at a cost to taxpayers of at least $1.5 trillion over the next ten years.

The American people are right to demand health-care reform. The current system is broken. But taken individually, most of the ideas currently being considered by Congress would make the problems we face even worse. Taken together, they amount to a complete government takeover of the American health-care system. That is not the type of reform most Americans seek.

— Michael Tanner is a senior fellow at the Cato Institute, author of Leviathan on the Right: How Big Government Conservatism Brought down the Republican Revolution, and co-author of Healthy Competition: What's Holding back Health care and How to Free It.

Thursday, May 14, 2009

Vitamins Found to Curb Exercise Benefits

Vitamins Found to Curb Exercise Benefits

If you exercise to improve your metabolism and prevent diabetes, you may want to avoid antioxidants like vitamins C and E.

That is the message of a surprising new look at the body’s reaction to exercise, reported on Monday by researchers in Germany and Boston.

Exercise is known to have many beneficial effects on health, including on the body’s sensitivity to insulin. “Get more exercise” is often among the first recommendations given by doctors to people at risk of diabetes.

But exercise makes the muscle cells metabolize glucose, by combining its carbon atoms with oxygen and extracting the energy that is released. In the process, some highly reactive oxygen molecules escape and make chemical attacks on anything in sight.

These reactive oxygen compounds are known to damage the body’s tissues. The amount of oxidative damage increases with age, and according to one theory of aging it is a major cause of the body’s decline.

The body has its own defense system for combating oxidative damage, but it does not always do enough. So antioxidants, which mop up the reactive oxygen compounds, may seem like a logical solution.

The researchers, led by Dr. Michael Ristow, a nutritionist at the University of Jena in Germany, tested this proposition by having young men exercise, giving half of them moderate doses of vitamins C and E and measuring sensitivity to insulin as well as indicators of the body’s natural defenses to oxidative damage.

The Jena team found that in the group taking the vitamins there was no improvement in insulin sensitivity and almost no activation of the body’s natural defense mechanism against oxidative damage.

The reason, they suggest, is that the reactive oxygen compounds, inevitable byproducts of exercise, are a natural trigger for both of these responses. The vitamins, by efficiently destroying the reactive oxygen, short-circuit the body’s natural response to exercise.

“If you exercise to promote health, you shouldn’t take large amounts of antioxidants,” Dr. Ristow said. A second message of the study, he said, “is that antioxidants in general cause certain effects that inhibit otherwise positive effects of exercise, dieting and other interventions.” The findings appear in this week’s issue of The Proceedings of the National Academy of Sciences.

The effect of vitamins on exercise and glucose metabolism “is really quite significant,” said Dr. C. Ronald Kahn of the Joslin Diabetes Center in Boston, a co-author of the report. “If people are trying to exercise, this is blocking the effects of insulin on the metabolic response.”

The advice does not apply to fruits and vegetables, Dr. Ristow said; even though they are high in antioxidants, the many other substances they contain presumably outweigh any negative effect.

Dr. Kahn said it might be that reactive oxygen is beneficial in small doses, because it touches off the body’s natural defense system, but harmful in higher doses.

Andrew Shao of the Council for Responsible Nutrition, a trade association of dietary supplement makers, said the new study was well designed but was just one bit of evidence in a complex issue. Most available evidence points to the opposite conclusion, that antioxidants benefit health by reducing oxidative stress, he said.

“I wouldn’t change recommendations for anyone based on one study,” he said. “This is one small piece of the puzzle.”

Wednesday, May 6, 2009

Nation's first face transplant patient reveals her face

Connie Culp, after an injury to her face, left, and after a face transplant, right. (Cleveland Clinic-HO Photo)

Connie Culp, before her injury in 2004.

Connie Culp, before and after the transplant. No information has been released about the donor or how she died, but her family members were moved when they saw before-and-after pictures of Culp, Dr. Siemionow said.
CLEVELAND -- Five years ago, a shotgun blast left a ghastly hole where the middle of her face had been. Five months ago, she received a new face from a dead woman.

Connie Culp stepped forward Tuesday to show off the results of the nation's first face transplant, and her new look was a far cry from the puckered, noseless sight that made children run away in horror.

Culp's expressions are still a bit wooden, but she can talk, smile, smell and taste her food again. Her speech is at times a little tough to understand. Her face is bloated and squarish, and her skin droops in big folds that doctors plan to pare away as her circulation improves and her nerves grow, animating her new muscles.

But Culp had nothing but praise for those who made her new face possible.

"I guess I'm the one you came to see today," the 46-year-old

Ohio woman said at a news conference at the Cleveland Clinic, where the groundbreaking operation was performed. But "I think it's more important that you focus on the donor family that made it so I could have this person's face."

Up until Tuesday, Culp's identity and how she came to be disfigured were a secret.Connie Culp, center, who underwent the first face transplant surgery in the U.S., is helped to the podium by her head surgeon, Dr. Maria Siemionow, right, as well as Renee Bennett, the nurse manager for the Clinic's transplant program, far left, and Pat Lock, a nurse with the transplant team, third from left, before speaking to the media at a news conference at the Cleveland Clinic in Cleveland, on Tuesday.

Culp's husband, Thomas, shot her in 2004, then turned the gun on himself. He went to prison for seven years. His wife was left clinging to life. The blast shattered her nose, cheeks, the roof of her mouth and an eye. Hundreds of fragments of shotgun pellet and bone splinters were embedded in her face. She needed a tube into her windpipe to breathe. Only her upper eyelids, forehead, lower lip and chin were left.

A plastic surgeon at the Cleveland Clinic, Dr. Risal Djohan, got a look at her injuries two months later. "He told me he didn't think, he wasn't sure, if he could fix me, but he'd try," Culp recalled.

She endured 30 operations to try to fix her face. Doctors took parts of her ribs to make cheekbones and fashioned an upper jaw from one of her leg bones. She had countless skin grafts from her thighs. Still, she was left unable to eat solid food, breathe on her own, or smell.

Then, on Dec. 10, in a 22-hour operation, Dr. Maria Siemionow led a team of doctors who replaced 80 percent of Culp's face with bone, muscles, nerves, skin and blood vessels from another woman who had just died. It was the fourth face transplant in the world, though the others were not as extensive.

"Here I am, five years later. He did what he said -- I got me my nose," Culp said of Djohan, laughing.

In January, she was able to eat pizza, chicken and hamburgers for the first time in years. She loves to have cookies with a cup of coffee, Siemionow said.

Connie Culp, before and after the transplant. No information has been released about the donor or how she died, but her family members were moved when they saw before-and-after pictures of Culp, Dr. Siemionow said.

Connie Culp, before and after the transplant. No information has been released about the donor or how she died, but her family members were moved when they saw before-and-after pictures of Culp, Dr. Siemionow said.

No information has been released about the donor or how she died, but her family members were moved when they saw before-and-after pictures of Culp, Siemionow said.

Culp said she wants to help foster acceptance of those who have suffered burns and other disfiguring injuries.

"When somebody has a disfigurement and don't look as pretty as you do, don't judge them, because you never know what happened to them," she said. "Don't judge people who don't look the same as you do. Because you never know. One day it might be all taken away."

It's a role she has already practiced, said clinic psychiatrist Dr. Kathy Coffman.

Once while shopping, "she heard a little kid say, 'You said there were no real monsters, mommy, and there's one right there,"' Coffman said. Culp stopped and said, "I'm not a monster. I'm a person who was shot," and pulled out her driver's license to show the child what she used to look like, the psychiatrist said.

The transplant team looks at a model of the patient's face during the first face transplant surgery in the U.S. on Connie Culp.

The transplant team looks at a model of the patient's face during the first face transplant surgery in the U.S. on Connie Culp.

Culp, who is from the small town of Unionport, near the Pennsylvania line, told her doctors she just wants to blend back into society. She has a son and a daughter who live near her, and two preschooler grandsons. Before she was shot, she and her husband ran a painting and contracting business, and she did everything from hanging drywall to a little plumbing, Coffman said.

Connie Culp, who underwent the first face transplant surgery in the U.S., said she wants to help foster acceptance of those who have suffered burns and other disfiguring injuries. Culp, who is from the small town of Unionport, near thePennsylvania line, told her doctors she just wants to blend back into society. Culp left the hospital Feb. 5 and has returned for periodic follow-up care. She has suffered only one mild rejection episode that was controlled with a single dose of steroid medicines, her doctors said. She must take immune-suppressing drugs for the rest of her life, but her dosage has been greatly reduced and she needs only a few pills a day.

The clinic expects to absorb the cost of the transplant because it was experimental, doctors said. Siemionow estimated it at $250,000 to $300,000. That is less than the $1 million that other surgeons estimate it costs them to treat other severely disfigured people through dozens of separate operations, she said.

Also at the Cleveland Clinic is Charla Nash of Stamford, Conn., who was attacked by a friend's chimpanzee in February. She lost her hands, nose, lips and eyelids, and will be blind, doctors said. Clinic officials said it is premature to discuss the possibility of a face transplant for her.

In April, doctors at Harvard-affiliated Brigham and Women's Hospital in Boston performed the nation's second face transplant, on a man disfigured in a freak accident. It was the world's seventh such operation. The first, in 2005, was performed in France on Isabelle Dinoire, a woman who had been mauled by her dog.

Friday, May 1, 2009

Swine flu has blindsided the world

What’s Different (and Dangerous) About Swine Flu?
Kara Rogers - April 29th, 2009

Swine flu has blindsided the world, and the participation of countries in the global effort to control the spread of the virus is now imperative in preventing a pandemic. But why has swine flu put the world on pandemic alert? And what is it about the swine influenza virus that suddenly set it apart from all other influenza viruses?

The first question is relatively simple to answer. The disease is highly infectious and contagious and can be deadly in humans. Furthermore, its outbreak in Mexico City and its subsequent spread to the United States present real opportunity for its spread to other countries worldwide. And, of course, such spread has already happened. With viral containment and isolation now impossible, we are on pandemic alert and must rely on controlling viral spread, rapid reporting of new cases, and warning against travel to and from affected areas to prevent a full-scale catastrophe.Domestic pigs.

However, the second question is much more difficult to answer, because the details of what make swine influenza virus so infectious in humans are largely unknown. The swine virus that is at the root of the current outbreak is called H1N1—the same labeling given to the virus that caused the devastating 1918-19 flu pandemic. But not all H1N1 flu viruses are created equally, and the swine virus appears to be quite different from all other H1N1 viruses.

Different strains of H1N1 are distinguished by any number of genetic variations, including many that affect the hemagglutinin (H) and neuraminidase (N) proteins found on the surface of the virus. In the case of the emergence of new swine H1N1 variants, several factors are at play, a major one of which is that pigs are susceptible to infection by swine, human, and avian influenza viruses. In addition, influenza viruses from different species have readily interchangeable segments of RNA. Thus, a pig simultaneously infected by human and avian viruses provides the perfect opportunity for a genetic swap between the different viruses.

An Influenza Perfect Storm

This scenario is not as far-fetched as it may seem. In fact, it is believed that sometime in the late 1990s, a sort of perfect storm involving swine, human, and avian influenza viruses took place in pigs in the United States. The result was a so-called triple reassortant swine influenza virus—part swine, part human, and part avian. As time passed, reassortant viruses mutated, and the genes affected were not always the ones encoding the H and N proteins of the viral coat. Mutations occurred in genes still largely unheard of in the public sector, genes like PB1 and PB2, which encode enzymes called RNA polymerases that function in viral replication.

Reassortant H1N1 swine virus appears to be more deadly in pigs than classical H1N1 swine virus, which was first isolated from pigs in the 1930s and did not possess genes from the human and avian viruses. The mutations in polymerase genes and in other viral genes are believed to further increase the virulence of swine influenza viruses, causing severe respiratory disease and death in pigs. Perhaps, the sicker the pigs the more likely the virus is to be spread to humans, whether through physical contact with sick animals or through inhaling infectious virus circulating in the air. Reassortant H1N1 swine influenza virus is common in pigs in the United States, and since the initial reassortant viruses emerged, the number of cases of human swine flu in the United States has increased annually.

A triple reassortant swine H1N1 virus appears to be the cause of the ongoing outbreak, and this virus is infectious and deadly in humans, particularly in people between ages 25 and 40. Why it is causing the death of presumably healthy adults remains unclear. However, all adult deaths from swine flu have occurred only in Mexico, despite the growing number of cases in other countries. This raises serious questions about the outbreak there, especially in light of the fact that adults elsewhere who are affected by the virus and who are treated within 30–48 hours of the onset of flu-like symptoms are experiencing full recovery from their illness.