Exercise best anti-aging treatment, study suggests

Canadian scientists appear to have proven that you can, in fact, run away from old age.

In what could stand up as the most powerful evidence yet that exercise prolongs life, a study by McMaster University researchers in Hamilton found that signs of premature aging were halted — and even reversed — in virtually every tissue and organ in the bodies of exercised mice.

The finding, which could be a turning point in anti-aging medicine, suggests the proverbial fountain of youth won’t come from a pill or from an exotic berry from the Amazon, but rather plain old exercise.

Mice genetically altered to age faster were forced to run on treadmills for 45 minutes, three times a week.

Five months later, the mice looked as young, healthy and active as wild-type mice — mice that didn’t have the genetic mutation — while their sedentary and same-aged siblings were balding, greying and shrinking.

While the exercised mice scampered and scurried about their cages, the aging non-runners huddled in a corner, barely moving.

Not only did the treadmill-running mice look as sleek-coated, bright-eyed and bushy-tailed as wild mice, but the researchers also saw “huge recovery” in age-related damage to practically every tissue they could analyze.

The study’s beauty lies in its simplicity, says principal investigator Dr. Mark Tarnopolsky.

“What’s neat about our study is that this is something that is conceivably so simple. We purposely exercised them three times a week for 45 minutes at a moderate-intensity exercise, which is something that any human — provided they don’t have . . . (an illness) — can do.”

What’s more, the exercise did more than just protect the muscles and heart, as might have been expected.

The team found “unprecedented” anti-aging effects of endurance exercise on the brain, skin, hair, gonads (ovaries and testicles), kidneys, spleen and liver.

“Every part of the body was protected by exercise,” said Tarnopolsky, a professor of pediatrics and medicine at McMaster’s Michael G. DeGroote School of Medicine. “I think that exercise is the most potent anti-aging therapy available today and likely forever.”

Death is inevitable, “but exercise is the only way to stay healthy and free of disease for a longer period of time,” he added.

“We know that exercise has benefits even when humans start over the age of 65. But this study clearly shows that we can get closer to the fountain of youth if we start when we’re young and do moderate exercise our whole life.”

The findings, published Monday in the journal Proceedings of the National Academy of Sciences, represents “one of the most striking rescues yet reported in aging models without gene therapy or a pharmaceutical intervention,” said lead author Adeel Safdar, a senior PhD student working with Tarnopolsky.

At the crux of the experiments lies the mitochondrial hypothesis.

The mice were genetically manipulated to age twice as fast as normal because of a defect in the repair system of their mitochondria, the powerhouses or furnaces inside each cell that give our body energy.

Evidence has been mounting for decades that the older we get, the more mutations we accumulate in mitochondrial DNA. The furnaces start to break down, resulting in a steady decline in tissue and organ function, Safdar said.

That not only leads to aging, he said, but also to all the diseases associated with getting older, including cancer, Alzheimer’s, diabetes and Parkinson’s.

“And that’s really the premise upon which these mice were created,” Tarnopolsky said. “The people who created the mice essentially said, ‘Why don’t we create a mouse that has mitochondrial dysfunction and see if they age prematurely?’ ”

Lo and behold, the mice die about twice as fast as normal mice and show many features of human aging, he said, including hair loss, hearing loss, cataracts, brain atrophy or shrinkage, enlarged hearts and smaller muscles.

Epidemiological studies in humans have shown that people who are physically active or exercise regularly have fewer chronic diseases and tend to live longer — runners especially.

“So we thought this was a nice model that would allow us to really test how effective exercise really is in human aging,” Tarnopolsky said.

The experiments began when the mice were three months old — about 20 in human years — and ended five months later when the mice were eight months old — in their late 60s by the human equivalent.

The mice were randomly assigned to running three times per week or to just being sedentary in their cages.

Five months later, the sedentary mice showed major signs of aging: Their ovaries and testes were small and their hearts were enlarged, compared to the running mice, whose hearts were essentially normal. “The brain was atrophic, or small in the non-runners, but it was back to normal size in the runners,” Tarnopolsky added.

It’s not clear exactly what’s happening. But exercise is a physiological stressor — a good one — that causes the body to produce more energy.

“In our study, we saw huge recovery in mitochondrial function (in the exercised mice),” Safdar said.

Bigger studies involving more mice are needed to determine just how strong the life-extending effect of exercise might be.

But, said Tarnopolsky, the message is “it’s never too late” to star exercising.

“I really think we have to start when people are young. We have to encourage our children and people throughout their life to maintain healthy levels of physical activity.”

Ottawa Citizen


Full article: http://www.ottawacitizen.com/health/Exercise+best+anti+aging+treatment+study+suggests/4324434/story.htmlhttp://www.ottawacitizen.com/health/Exercise+best+anti+aging+treatment+study+suggests/4324434/story.html

Doctors Mystified by Case of World’s Thinnest Woman

8,000 Calories a Day

Lizzie Velasquez is a mystery to doctors.

Texas native Lizzie Velasquez, 21, is thinner than anyone thought possible. She spends her days wolfing down burgers, fries and cake, consuming more than three times the normal calorie requirements. Doctors can’t explain how she can be so underweight and still alive.

She starts the day with corn flakes or a burrito. An hour later, 21-year-old Lizzie Velasquez is already snacking on potato chips or cookies. Soon afterwards, she eats fried chicken with French fries or a pizza. By lunchtime, Velasquez has already consumed about 4,000 calories, as much as the average road worker or miner burns in an entire day.

What 8,000 calories means

The same pattern continues throughout the rest of the day. Velasquez likes it when whatever she has on her plate is covered with plenty of melted cheese. By the time the native Texan goes to bed, the caloric value of the food she has eaten that day corresponds to about 8,000 calories.

The same procedure has repeated itself day after day for years. With that kind of diet, one would image the young woman would be so obese that she could barely leave her home. But the opposite is true. Lizzie Velasquez is so thin that strangers sometimes knock on the door of the family home to angrily inform her parents that they should feed their daughter properly.

Of course, these people have no way of knowing that Velasquez has probably already consumed as much food in her young life as her mother, who is twice her age.

Zero Body Fat

Nevertheless, Velasquez has no fat at all on many parts of her body — which, in her case, literally means zero fat. That is in contrast to, say, bodybuilders who claim to not have a single gram of fat on their body when they still have about 6 to 8 percent body fat.

But because Velasquez, unlike bodybuilders, has hardly any muscle mass either, she looks as if her skin were stretched directly across her skeleton. She walks on stilt-like legs and her handshake is as light as can be. But apart from her extremely low body weight — about 62 pounds (28 kilograms) at a height of 5 foot 2 inches (157 centimeters) — Lizzie Velasquez is doing well. Her condition will not deteriorate as long as she continues to eat enough.

Her metabolism is a mystery. What happens to all the energy from the fast food Lizzie consumes? Doctors don’t know the answer. All they know is that Velasquez is part of a tiny minority on the planet, probably only a handful of people, who can eat as much of whatever they want without gaining weight.

Is the mysterious anomaly a disease, a syndrome, a genetic defect — or even a gift, as Velasquez calls it? Some have already speculated that the body of this young woman from Texas could hold some sort of magical formula — a “thinness gene,” if you will — that many an overweight person would love to have.

Cheeseburgers without Regret

Human metabolism has in fact been thoroughly studied, and nutrition science yields new revelations week after week. They fill the pages of glossy women’s magazines in the form of diet tips, some of which are controversial. Nevertheless, experts still cannot offer a satisfactory explanation of why some gluttons stay thin while less fortunate people gain weight even if they are relatively modest eaters.

Velasquez has girlfriends who envy her for her ability to eat several cheeseburgers in a row without regret. But this form of recognition is relatively new. For most of her life, Velasquez was either ridiculed or pitied because of the way she looks.

Faced with such adversity, she developed a defiant sense of pride. She insists that she wouldn’t want to change anything about her condition, even if there were the prospect of a cure. “The syndrome is worth every negative experience,” she says. “I don’t want to look like everyone else.”

The mysterious ailment has never occurred in her family before. Velasquez’s younger siblings — her brother Chris and her sister Marina — have developed normally. Her parents Lupe and Rita, who are religious, allowed Lizzie to grow up with the knowledge that fate had dealt her a special hand.

This outlook is reflected in the title of a book Velasquez has written: “Lizzie Beautiful.” Not surprisingly, the book’s publication triggered media interest in the emaciated woman.

Too Strong to Die

As a young girl, Velasquez appeared as a guest on several television programs. Some audience members reacted to the hyper-thin child, with her thick glasses, the way visitors to a fair in Victorian London once must have gawked at Joseph Merrick, the severely deformed man known as the Elephant Man. Unable to bear the horrifying otherness they were witnessing, many visitors, then and now, tried to compensate for their discomfort by making absurdly vulgar remarks.

Velasquez already attracted attention at her birth. She weighed 2 pounds, 10 ounces (1,190 grams) and was only 16 inches (40 centimeters) long. “I fit into a small shoebox,” she says. Far more disconcerting was the fact that the newborn had no fatty tissue at all. Her arteries were clearly visible under her skin, and her head resembled that of a crudely carved wooden doll.

Doctors did not think that the little girl would survive. But then, to everyone’s surprise, it turned out that all of her internal organs — lungs, heart, liver and intestines — were fully functional. Apparently Velasquez was too strong to die.

Surprising the Doctors

A detective-like search for the essence of her mysterious ailment began. But the effort was in vain. Doctors couldn’t figure out what the girl lacked.

They told the parents that their daughter would never be able to walk or talk. When Velasquez was four, doctors discovered that she was blind in her right eye. Her vision was also significantly restricted in her left eye.

But Lizzie could walk — and talk. And she did grow. The only problem was that she was unable to gain any weight. The taller she became, the more emaciated she looked.

Lacking answers, the doctors had only one piece of advice for the parents: “Keep an eye on your daughter, and get in touch with us if anything seems strange.”

But everything about her was already strange.

Too Thin to Be Alive

When Lizzie was 13, her mother wrote an account of her daughter’s condition in a medical newsletter, which attracted the attention of Abhimanyu Garg at the University of Texas Southwestern Medical Center in Dallas, who contacted the Velasquez family. Garg, an internist, specializes in the study of diseases relating to human metabolism. Since then, he has paid regular visits to the Velasquez home, keeping track of Lizzie Velasquez’s progress from a medical perspective. 

Garg examined the then-adolescent more extensively than any other doctor before him. Velasquez’s bone density was measured using a scanning method called dual-energy x-ray absorptiometry. Garg performed a biochemical analysis of her metabolism and examined her entire body using magnetic resonance tomography. The results showed that Lizzie Velasquez is surprisingly healthy for a young woman who in theory is too thin to be alive.

A body mass index (BMI) value of 20 to 25 is considered normal. Someone with a BMI of less than 16 is considered critically underweight. Velasquez has a BMI of 10.9.

Normal Development

Garg was the first to come up with a name for the strange disorder, calling it neonatal progeroid syndrome (NPS). It is an extremely rare condition that was first described in the mid-1970s by Thomas Rautenstrauch, a German pediatrician.

Rautenstrauch had reported on babies that were severely underweight and with prematurely aged faces, beak-like noses, thin hair and growth disorders. Longer-term observation of the small, horribly disfigured patients was often impossible, because most died in infancy. The few that did grow older soon exhibited a pronounced mental deficiency.

Even though the external symptoms of NPS apply to Velasquez, her brain has developed normally. And at 5 foot 2 inches, she isn’t even particularly short for a woman of Mexican descent.

Taste for Junk Food

The number of NPS cases worldwide ranges from 30 to 60. Velasquez is even unusual within this small group. There are only two other known cases of females in whom the condition has taken a similarly atypical course. Coincidentally, one of them lives in Austin, like Velasquez, and is about 14 years old. The second is a woman in her 30s who lives in Great Britain. Unlike Velasquez, these two women have decided to avoid the public eye.

Probably no other scientist has illuminated the rare syndrome as thoroughly as Abhimanyu Garg. He believes that the disease is genetically determined, although he is unable to name a specific gene that’s involved. Garg also has no hopes for a cure. He doesn’t even know what advice to give a patient like Velasquez to keep herself reasonably healthy.

Meanwhile, her only option is to keep on feasting. “I’m extremely picky when it comes to food,” Velasquez confesses. She never eats salad and doesn’t touch fruit, either. Her eating behavior corresponds to the clichéd image of the US teenager who eats nothing but junk food.

“Thank God I can get away with it,” she says, neglecting to mention the fact that her body, like anyone else’s, also suffers from the effects of unhealthy eating. For example, she recently had to stop drinking soft drinks because her blood sugar levels had become so high.

‘Make Sure She Eats’

Velasquez also largely dismisses the notion that it must be a burden to have to eat three to four times as much as a normal person throughout the day. But sometimes she can’t hide the fact that her high-calorie diet can be tiresome.

“She’s a typical 21-year-old who doesn’t always do what she should,” says Joe Caruso, who helps her with media inquiries. When the two travel together, he has a special responsibility. “This morning Lizzie’s mother said to me: ‘Make sure she eats,'” he says.

Caruso occasionally disappears for a minute, only to return with a piece of cake, which he hands to Lizzie as if it were medicine. She chews without pleasure — as if it really were her medication.

No one can say what actually happens to all the nutrients in Velasquez’s body. In healthy individuals, some of the nutrients would be converted into fat deposits. But the energy in the food she eats apparently does have some effect. When she doesn’t eat, she becomes tired quickly and her immune resistance declines rapidly.

Hunger Pangs

A reporter once wrote that she has to eat a meal every 15 minutes. Nonsense, says Lizzie. It is true, however, that she feels hungry far more often than normal people do. If she ignores the impulse, her energy level soon plummets. Because she has no reserves at all, a lack of food becomes quickly and seriously noticeable.

As a child she often suffered from ear infections — possibly because she wasn’t able to make people understand the importance of her frequent hunger pangs. She often spent weeks at a time in bed, worn out by an ordinary cold.

Hasn’t she ever dreamed of being strong and powerful? “I never really saw a need for that,” she claims. Her mother once sent her to a gym, hoping that Lizzie could lift weights to strengthen her muscles. Garg intervened. His patient perspires heavily during physical exercise and can easily become dehydrated.

Garg is about to repeat all the tests he has already performed on her once before. They are the helpless attempts of a man who faces a mystery he is unable to solve.

‘A Huge Gift’

Lizzie is amused by the idea that she will go down in medical history as a living miracle. She is also aware that she could become a curiosity handed from one doctor to the next. Or she could become a sort of trophy case that brings fame to a particular doctor.

But none of this troubles her. After spending many years in and out of various laboratories and doctors’ offices, she no longer has much faith in anyone solving the mystery. And she repeatedly insists that she isn’t interested in a cure. “This is a gift, a huge gift, an honor,” she says, referring to her disease.

Then it’s time for her to go. She’s tired, and she feels cold.

It’s noon in her native Austin, and the temperature is 40 degrees Celsius (104 degrees Fahrenheit) in the shade.


Full article and photos: http://www.spiegel.de/international/zeitgeist/0,1518,729805,00.html

The Workout Enigma

Recently, researchers in Finland made the discovery that some people’s bodies do not respond as expected to weight training, others don’t respond to endurance exercise and, in some lamentable cases, some don’t respond to either. In other words, there are those who just do not become fitter or stronger, no matter what exercise they undertake. To reach this conclusion, the researchers enrolled 175 sedentary adults in a 21-week exercise program. Some lifted weights twice a week. Others jogged or walked. Some did both. Before and after the program, the volunteers’ fitness and muscular strength were assessed. At the end of the 21 weeks, the results, published earlier this year in Medicine and Science in Sports and Exercise, were mixed. In the combined strength-and-endurance-exercise program, the volunteers’ physiological improvement ranged from a negative 8 percent (meaning they became 8 percent less fit) to a positive 42 percent. The results were similar in the groups that undertook only strength or only endurance training. Some improved their strength enormously, some not at all. Others became aerobically fitter but not stronger, while still others showed no improvements in either area. Only a fortunate few became both fitter and more buff. As the researchers from the University of Jyvaskyla wrote with some understatement, “large individual differences” exist “in the responses to both endurance and strength training.”

Hidden away in the results of almost any study of exercise programs is the fact that some people do not respond at all, while others respond at an unusually high rate. Averaged, the results may suggest that a certain exercise program reliably will produce certain results — that jogging, say, three times a week for a month will improve VO2max (maximal oxygen capacity) or reduce blood pressure; and for almost any given group of exercisers, those results are likely to hold true. But for outliers, the impacts can be quite different. Their VO2max won’t budge, or it will fall, or it will soar.

The implications of such wide variety in response are huge. In looking at the population as a whole, writes Jamie Timmons, a professor of systems biology at the Royal Veterinary College in London, in a review article published last month in The Journal of Applied Physiology, the findings suggest that “there will be millions of humans that cannot improve their aerobic capacity or their insulin sensitivity, nor reduce their blood pressure” through standard exercise.

But what is it about one person’s body that allows it to react so vigorously to exercise, while for others the reaction is puny at best? One answer, to no one’s surprise, would seem to be genetics, although the actual mechanisms involved are complex, as a recent study by Dr. Timmons and others underscored. In that work, researchers accurately predicted who would respond most to endurance exercise training based on the expression levels of 29 different genes in their muscles before the start of the training. Those 29 genes are not necessarily directly associated with exercise response. They seem to have more to do with the development of new blood vessels in muscles; they may or may not have initiated the response to exercise. Scientists just don’t know yet.

In other words, this issue is as intricate as the body itself. There is a collection of compelling data that indicate that about half of our aerobic capacity “is genetic,” Dr. Timmons wrote in an e-mail. “The rest may be diet,” or it could be a result of epigenetics, a complicated process in which the environment (including where you live and what you eat) affects how and when genes are activated. “Or it could be other factors,” he said. Although fewer studies have examined why people respond so variously to strength training, “we have no reason to doubt,” he said, that genetics play a similar role.

But none of this means that if you once took up jogging or weight lifting and didn’t respond, you should take to the couch. It may be that a different exercise regimen would prompt beneficial reactions from your particular genome and physiology, Dr. Timmons said. (Although scientists still have a long way to go before they can say, definitively, who needs what exercise, based on genetic and other differences.) In the meantime, Dr. Timmons stressed, even low responders should continue to sweat. Just as scientists don’t yet understand the complicated underpinnings of the body’s response to exercise, they also don’t necessarily understand the full range of exercise’s impacts. Even if you do not increase your VO2max, Dr. Timmons said, you are likely to be deriving other benefits, both big and small, from working out. Exercise does still remain, “on average,” he said, “one of the best ‘health’ treatments we have.”

Gretchen Reynolds, New York Times


Full article and photo: http://well.blogs.nytimes.com/2010/11/17/phys-ed-the-workout-enigma/

Scourge of Humankind

High-profile efforts to fight malaria confront an ever-changing enemy that has evolved alongside man

Bad Air. Even the word “malaria” tells us that the disease caused by the plasmodium pathogen is out of the ordinary. The name “Mal-Aria” didn’t come into common medical usage until about 300 years ago, but for many more centuries “swamp fever” expressed the same thing: a serious disorder that assaulted the human body and especially the brain. Associated with bad drainage, water-logged soil and damp climate, it was the quintessential disease of location.

Location still matters a great deal in the incidence of malaria, but it is no coincidence that the most intensely malarious locations in the world today—sub-Saharan Africa, Southeast Asia, parts of South America—are also some of the poorest. This connection between poverty and malaria is undeniable, but their causal chain is problematic. Does malaria cause poverty through premature death, chronic disability and low productivity? Or does poverty itself cause the social chaos and unhealthy conditions that permit malaria to take a stranglehold on a town, region, country and even a continent? This seemingly straightforward question has been fiercely debated for a century and more.

Siblings in Cambodia take protection beneath insecticide-laced anti-mosquito netting.

Ronald Ross, who won the 1902 Nobel Prize for medicine for his demonstration that malaria is transmitted by Anopheles mosquitoes, firmly believed that malaria causes poverty. Get rid of malaria and malarious areas of the world will begin to prosper. Jeffrey Sachs, the outspoken economist who heads Columbia University’s Earth Institute, has inherited Ross’s modern mantle. Other economists (and malariologists) have not been so certain. In many parts of the world, including Britain and the U.S., malaria lost its hold only as prosperity was gradually achieved. Malaria’s disappearance was a welcome byproduct of better nutrition, schools, roads, health care and methods of agriculture.

These two interpretations translate into two differing medical approaches to the disease—vertical and horizontal. A classic vertical response was the initial campaign by the World Health Organization, in the 1950s and 1960s, to eradicate malaria through the use of the insecticide DDT. Following its abandonment, there were strong calls among international health workers to go down a “horizontal” route: If prosperity brings health along with it, Western aid for developing countries ought to be devoted to helping provide modern infrastructure.

The results of the horizontal approach have been patchy at best. Childhood mortality in sub-Saharan Africa has been staggeringly intransigent. A million deaths is the figure typically reported for mortality world-wide, but that may not have much substance in reality, as investigative journalist Sonia Shah notes in “The Fever: How Malaria Has Ruled Humankind for 500,000 years.” We don’t know how many people die from malaria, or even die with the disease. What we do know is that current inroads against malaria are piecemeal and may not be sustainable.

Now the arrival of Bill and Melinda Gates on the international health scene has changed everything, placing a renewed emphasis on the vertical approach. The founder of Microsoft admirably wanted to put some of his vast fortune back into society, and “neglected diseases” (including malaria, AIDS, and drug-resistant tuberculosis) seemed to be a good place to start. Melinda Gates, in particular, has placed malaria eradication back on the agenda, and the Gates Foundation funds research toward improved drug treatments, safer insecticides and eventually an effective vaccine. But the lessons of history should give us pause.

Back in the 1930s, thoughtful malariologists such as S.P. James, who had worked in India shortly after Ross, believed that it was ill-advised even to attempt eradication in regions with high incidence of the disease. Despite the high infant mortality that malaria causes, individuals who survive the disease acquire sufficient immunity to cope as adults. Destroying that herd immunity, even for a generation, means risking that the disease will return with a vengeance.

Doctors like James and others who advised the League of Nations Malaria Commission also appreciated how complex malaria actually is. Four different species of parasites can cause it, and each evokes a different response in its human host. More than two-dozen species of Anopheles mosquitoes can transmit the parasite, and each species has its own breeding patterns and favored habitat. The consequence, as malariologist Lewis Hackett (1884-1962) wistfully wrote in the 1930s, is that malaria is “so moulded and altered by local conditions that it becomes a thousand different diseases and epidemiological puzzles.” The treatment that works best in one location may not work elsewhere—and “elsewhere” may be only a few miles away.

DDT briefly seemed to make these insights irrelevant. It formed the bedrock of the World Health Organization’s postwar campaign and achieved a good deal more than it is often given credit for. By 1963, when the funding for the DDT drive dried up amid concerns about the insecticide’s ecological effects, malaria had been eliminated from Europe, the U.S. and many other parts of the world. It had been almost eradicated from India and Sri Lanka.

In the rich countries it has stayed away—barring imported cases. In Asia, the gains quickly evaporated. India was down to about 50,000 cases when the spraying ended. By 1969 it had zoomed back to one million. Yet the WHO initiative may have failed even if it had been continued, due to the cunning adaptations of the enemy. The mosquitoes gradually grew resistant to DDT, while the parasites themselves became resistant to anti-malarial drugs such as chloroquine and atebrin.

All these issues, and many others, are brilliantly exposed in Ms. Shah’s book. She has read widely and appreciates the enormous efforts that even the modest goal of better malaria control will entail. Because she understands malaria’s history, she is also skeptical that the present eradication campaign will succeed, at least in the short term. Already some problems that bedeviled previous “vertical” efforts have raised their heads again.

Mosquitoes seem to be getting used to pyrethrum, the insecticide used to impregnate bed nets. (The nets are also not always used for the job they are designed for—having been discovered to be helpful in fishing and worth a bit of money on the black market.) Likewise, resistance to artemisinin-based treatments is beginning to be reported. Drugs are distributed but patients do not finish the course, stopping when they feel better or sharing the drugs with their friends and family. Self-medication is also a serious issue, since many drugs bought privately are fakes or contain a fraction of the medicine required. Inadequate dosing increases the probability that drug resistance will emerge in the parasites.

Supporters of a “horizontal” approach can point to even more basic problems. In many countries, the infrastructure for effective treatment is missing: Hospitals are often little more than makeshift facilities where patients come in hope or despair. The medications themselves are more expensive than most governments can afford, which is why international aid agencies and private philanthropy such as the Gates Foundation are attempting to bridge the gaps.

These groups are also, as we learn in Bill Shore’s “The Imaginations of Unreasonable Men,” backing a more ambitious approach: the development of a malaria vaccine. Mr. Shore, the well-known founder of Share Our Strength, a charity aimed at eliminating childhood hunger in the U.S., here provides an upbeat account of several American scientists researching malaria prevention. He and Sonia Shah sit at opposite ends of the inter national malaria problem—the vertical visionary and the horizontal historian. I prefer to the sober analysis of Ms. Shah to the well-meaning hype of Mr. Shore, but Mr. Shore tells his story well, making a virtue of his own studied naïveté in order to explain current efforts for a general reader.

What comes through very clearly is that the Gates money has transformed American malaria research. “The Gates Foundation very much acts like the general contractor responsible for eradicating malaria,” Mr. Shore writes, “using a wide variety of subcontractors who specialize in vaccines, drugs, diagnostic techniques, and public health systems.” Mr. Shore’s profiles thus include several recipients of Gates’s generosity, including Amyris Biotechnologies and the Institute for OneWorld Health. Sanaria, a start-up developing a malaria vaccine (one of 35 candidates currently tracked by WHO), might not have been able to continue its work without a timely Gates grant.

All the new ideas and energy coming from America have inevitably raised hopes, around the world, that perhaps Yankee ingenuity really can crack the malaria problem in the laboratory. The scientists themselves certainly seem confident. But should they be? Most malariologists agree that malaria cannot be eliminated without a vaccine. But that does not mean that a vaccine will necessarily eliminate malaria.

The depressing fact is that both mosquito and parasite are highly adaptable, and malaria has been central to human life for (to borrow from Ms. Shah’s subtitle) 500,000 years. Our battles with it have been written into the human genome: Sickle cell anaemia and other similar disorders, for instance, are genetic evidence of how humans and malaria have evolved together. Given this history, it is optimistic to think that the disease can be easily stamped out, especially considering that whatever magic solution might be discovered will still need to be delivered via a social infrastructure that doesn’t exist in much of the world.

The danger of the latest eradication attempt is that, with even the best will in the world, private philanthropy may not have staying power. The slog will be long and hard and the results slow in developing. We must not be paralyzed by the past. Nevertheless, the international health industry needs to set attainable goals—or risk repeating the failures of the initial malaria eradication program, which stopped when the money ran dry.

In most of the world today, malaria is a disease of poverty, and any doctor knows that the best way to get rid of a disease is to attack its cause.

Dr. Bynum is professor emeritus of the history of medicine at University College London.


Full article and photo: http://online.wsj.com/article/SB10001424052748703326204575616452789851046.html

The Headache That Wouldn’t Go Away

“My arm — something is biting my arm!” The 26-year-old woman struggled to sit up in bed. What’s wrong? her husband asked, alarmed and suddenly wide awake. His wife didn’t seem to hear him. Suddenly, her whole body began to jerk. Although he had never seen a seizure, the young man knew immediately that this was one. After a long and terrifying minute the jerking stopped and his wife lay quiet with her eyes closed, as if she were asleep. When he couldn’t wake her, he picked up the phone and dialed 911.

In the emergency room, the young woman was sleepy and confused. She didn’t remember the seizure. All she knew was that she felt bad earlier that day. Her shoulders ached and she had these strange shooting pains that ran up her neck, into her skull. She had a wicked headache too. Although she had this headache for months, it was much worse that day. At home she took a long hot bath and went to bed. She woke up in the ambulance.

She’d had no fever, she told the E.R. doctor, and hadn’t felt sick — just sore. And now she felt fine. Her arm didn’t hurt — in fact she couldn’t remember that it had ever hurt. She still had the headache, though. She didn’t smoke, didn’t drink and took no medications. She moved to Boston from Bolivia several years earlier to get married and now had 15-month-old. Other than mild confusion, the patient’s physical exam was normal. The E.R. doctor ordered blood tests to look for evidence of infection along with a CT scan of her head to look for a tumor.

Her headache started the year before, when she was pregnant. Before that she had the occasional headache, but back when her daughter was barely a bump, she got one that simply never went away. She told the midwife, who said it wasn’t unusual to get headaches during pregnancy. But to the patient, this headache seemed different. It was like a vise on her head, just over her eyes. The pressure wasn’t excruciating, just unrelenting. She took Tylenol, and that sometimes helped, but the headache always came back. Sometimes it even woke her up in the middle of the night. Finally the midwife sent her to her primary-care doctor.

Her doctor, a young internist in her first year of training (who asked that her name not be used), was worried about this headache. It had persisted for weeks and woke her patient up from sleep — that was unusual. The doctor recalled how happy the patient was when she called her with the news of her positive pregnancy test. And now barely showing at five months, she looked like the picture of expectant health. Had she had any weakness or numbness? Was there any loss of hearing or blurry vision? No, no and no. Well, she did have blurry vision, but that’s only because she hated wearing her glasses.

The doctor focused her exam to look for any hint that this headache might be because of some kind of brain injury. She looked into the patient’s eyes with the ophthalmoscope, scanning the retina for any signs of increased pressure inside the brain. She checked the patient’s strength, coordination and reflexes. Nothing. Her exam was completely normal.

Headaches are common, accounting for some 18 million doctor visits a year. Most are completely benign, but up to 3 percent of patients with a headache severe enough to send them to the emergency room will have something worth worrying about. Doctors are taught to look for three types of potentially dangerous headaches: the first, the worst and the cursed. The first headache in someone who doesn’t have headaches; the worst headache ever in someone who does; or a headache “cursed” by symptoms like weakness or numbness. A CT scan should be considered for these possibly life-threatening headaches. This headache fit into none of these informal categories.

This patient was woken up from sleep by her headaches — that’s unusual, but the doctor knew that it was not one of the recommended reasons for getting a CT scan. And she was pregnant. A CT scan of the head requires a relatively high dose of radiation. Was the doctor’s concern great enough to risk exposing the fetus based only on this somewhat unusual symptom? Not yet. Especially since there was another possible cause of the persistent headache — eyestrain. The patient was no longer wearing her glasses; she didn’t even own a pair, she confessed. She should get new glasses, the doctor suggested, and see if wearing them helped her headache. If not, she should come back. Perhaps they would get a CT scan at that point.

It was more than a year later when the patient next came to see the doctor. She had gotten glasses, and though the headaches hadn’t stopped, they seemed a bit better. It was no longer a constant pain. She had one maybe three to four times a week, and it lasted for a few hours and went away with a little ibuprofen. Besides, she was really too busy with the baby and her job to worry too much about them.

Then, six months after that last visit, she had this middle of the night seizure. In the E.R., the blood tests were all normal. Not so the CT scan. On the right side of the patient’s brain, just over the eye, there was a bright circle of white, the size of a dime. Not a brain tumor. No, the radiologist said, this was a tiny worm, a larvae, the young offspring of a tapeworm. The parasite, known as Taenia solium, is transmitted through undercooked pork contaminated by tapeworm eggs. Once in the body, the eggs hatch and then attach themselves to the intestinal wall and within a few months can grow to up to 15 feet or more. A mature tapeworm will then release hundreds of eggs into the gut every day. If any of these are ingested, they can hatch, enter the bloodstream and, once there, can lodge almost anywhere in the body, although they usually end up in muscle and in the brain.

Although unusual in the United States, pork tapeworm is common in the developing world. And having these larvae in the brain, a condition known as neurocysticercosis, is the most common cause of adult epilepsy in South and Central America. The patient was probably infected with this tapeworm years earlier when she lived in Bolivia. This kind of infection can be asymptomatic for years. Once the doctors saw the CT scan, the patient was treated with an antiparasite medication for 30 days and started on antiseizure medications.

When her primary-care doctor heard that her patient had been diagnosed with neurocysticercosis, she scoured the patient’s hospital chart and then her own notes. How had she missed that? What should she have done differently? She discussed the case with several of her teachers, who assured her that she had done everything properly. One of the frustrating truths in medicine is that it is possible to do everything right and still be wrong and miss the diagnosis.

The young doctor called the patient to see how she was doing and to schedule a follow-up visit. She was disappointed, though not completely surprised, when the patient chose to see a different doctor at the clinic.

In thinking about this case, the doctor’s greatest regret is that she didn’t get the chance to follow up on her patient and find out that her headaches didn’t go away by just wearing glasses. When patients don’t come back, the temptation is to assume they’ve gotten better. That is often not the case. Sometimes they’ve just given up. Now when she has a patient she is worried about, the doctor doesn’t tell them to call her if they don’t get better. Instead she has them make an appointment to come back in a couple of weeks. “If they are all better,” the doctor told me, “they can cancel the appointment. But just in case they aren’t — the way this woman wasn’t — they can come back, and I can have another shot at the whole thing.”

Lisa Sanders is the author of “Every Patient Tells a Story: Medical Mysteries and the Art of Diagnosis.”


Full article and photo: http://www.nytimes.com/2010/11/07/magazine/07FOB-Diagnosist-t.html

With hope, farewell fear


The long struggle to understand cancer

The Emperor of All Maladies: A Biography of Cancer. By Siddhartha Mukherjee. Scribner; 541 pages.

Here’s how they look in the lymph

IT IS said that when the good burghers of Amsterdam were first presented with a rhinoceros—armoured, horned, three-toed, with a prehensile lip—spectators shook their heads in disbelief. Cancer provokes a similar bafflement. So protean are its forms and so varied its features that even specialist prognoses of aggressiveness, invasion and response to treatment have typically generated more exceptions than rules. Apparently identical cancers in two patients may behave so unlike as to appear utterly different diseases. Siddhartha Mukherjee’s “The Emperor of All Maladies” tells of the search for a “unifying theory” of cancer, the common attribute of all types of malignant cell growth that might reveal its cure.

The arc of this rich and engrossing book matches Mr Mukherjee’s personal evolution as an oncologist, beginning on the first day of his hospital residency. It seems that the diversity of this implacable, shape-shifting foe will defeat him. He is faced with dead-end discoveries, therapeutic disasters and revelations that lead only to more mysteries. But with the perceptiveness and patience of a true scientist he begins to weave these individual threads into a coherent and engrossing narrative.

The earliest references to cancer, in 2600BC or so by Imhotep, an ancient Egyptian physician, then by Hippocrates and Galen, were simple clinical descriptions: swelling, ulceration, death. These were attributed to “humours” or blockages of bile. In the mid-19th century, a pioneering German pathologist, Rudolf Virchow, identified one feature of cancers: that they represent an uncontrolled proliferation of cells. The cause may still have been a mystery, but the search began for cures.

Surgeons brandished the knife, cutting ever wider and deeper, but recurrence of the disease suggested that the operations had been too conservative, that even more extensive procedures stood more chance of cure. As the science of pathology advanced and leukaemias and lymphomas became recognised as cancers of blood cells, it became clear that the entire bone marrow or lymphatic system could not be extirpated (although some physicians tried). Chemotherapeutic drugs were used, singly and then in increasingly lethal combinations to try to destroy all abnormal cells. X-rays and other forms of radiation were known to kill cells and these were aimed at lymph glands near and distant, on sites of secondary cancer spread in bone and lung and brain.

Practitioners in each field claimed advances. Individual lives were saved. Scientific optimism after the second world war led a leading American oncologist, Sidney Farber, to talk in 1962 of the underlying “singularity” of cancer, and to postulate a “universal cure”. Screening programmes for breast and cervical cancer promised detection at an earlier stage, with improved outcomes. In 1985 American epidemiologists conducted a review of the benefits of these advances in diagnosis and treatment. In the previous year there had been 211 deaths and 448 new cancer cases diagnosed for every 100,000 Americans. When these were compared with the figures for 1962, it was evident that this war was not being won; cancer-related deaths had increased by 8.7%. Much of this could be traced back to the lung-cancer epidemic that had followed the surge in smoking in the 1950s, but the message was clear. More needed to be understood about cancer’s causes before true advances could be made on the curative front.

Scientists had not been idle, but the significance of their labours remained obscure. A virus had been found to cause a cancer in chickens. A rare eye tumour sometimes manifested itself in members of the same family. Certain occupations seemed to breed malignancy; chimney sweeps historically got cancer of the scrotum, dye manufacturers bladder cancer and wartime shipyard workers handling asbestos died from aggressive tumours of the membrane lining the chest. Radium, that source of X-rays used to treat some cancers, had induced fatal malignancies in Marie Curie and her fellow researchers. There was the explicit association between cigarettes and lung cancer, while the newest disease, AIDS, sometimes appeared as multiple malignant tumours called Kaposi’s sarcoma. What common process could be understood from these apparently unconnectable discoveries?

It was time to return to fundamentals. Instead of replicating to an organised plan and forming normal tissue, cancer cells multiply madly. They secrete compounds that induce a proliferation of blood vessels that feed their growth and allow them to infiltrate the walls of adjacent organs. These attributes are genetically programmed functions of normal cells that are intended to combat infection or repair injury. They are controlled by molecular triggers that switch on and off on demand. The common aspect of the apparently disparate causes of cancer is that they induced genetic damage, locking these switches full on. Chaotically multiplying, the abnormal cells mutate, evolving myriad new characteristics: resistance to chemotherapy or an ability to establish colonies in distant parts of the body. The unifying theory had been found.

No longer is the topography of cancer formless flesh, unbridled and invading, but a complex scaffold of cancer DNA that affords binding sites for molecular therapies to block or reset aberrant cellular switches. Twenty-four new drugs are already in use, targeting specific mutations of lung, breast, colon, prostate and blood-cell malignancies. Researchers have hundreds of others in trial. Surgery, radiotherapy and chemotherapy treatments advance constantly.

Cancer’s endless mutability, its ruthless adaptation to survive, is being matched by resourcefulness. The epitaph of the emperor of maladies has not been written quite yet, but his all-conquering domain is in perceptible retreat.


Full article and photo: http://www.economist.com/node/17413995

Hospitals Have Hope in Dutch ‘Search and Destroy’ Strategy

Combating Deadly Bacteria

An electron micrograph image of clumps of methicillin-resistant Staphylococcus aureus bacteria, commonly referred to by its acronym, MRSA. The “killer bug” has become commonplace in German hospitals, where it infects one in 70 patients in the average intensive care unit. So-called “multiresistant pathogens” are a serious problem in Germany and other countries

Every day, several people die in German hospitals after being infected with bacteria resistant to most antibiotics. Though the threat is growing, a strategy long-used in the Netherlands is catching on and raising hopes.

When Germans are admitted into Dutch hospitals, they are usually surprised to learn that they will be placed under quarantine. Doctors and nurses will only approach them after donning protective gowns, gloves and surgical masks.

In the Netherlands, Germans are considered an infection risk because their hospitals, nursing homes, rehabilitation centers and dialysis stations back home are full of so-called “multiresistant pathogens” — in other words, bacteria that have grown resistant to almost all antibiotics.

One Dangerous Bacterium

In particular, the “killer bug” MRSA — short for methicillin-resistant Staphylococcus aureus — has become almost commonplace in German hospitals, where it infects one in 70 patients in the average intensive care unit (ICU). Likewise, although MRSA infections are starting to level off — albeit at a high level — there has been a marked increase in so-called ESBL-producing intestinal bacteria (with ESBL being an abbreviation of “extended spectrum beta-lactamase”). These bacteria produce an enzyme that can destroy penicillins, cephalosporins and other antibiotics. Indeed, the Robert Koch Institute, Germany’s leading institution for disease control and prevention, estimates that the country sees at least four unnecessary deaths every day as a result of infections acquired in hospitals.

A Life-Threatening Scratch

“At first it was only a little scratch, here, on my lower leg,” says Emma P., 83, who lives near the northwestern German city of Münster. But that seemingly harmless injury was just the beginning of an ordeal that would last for months.

After being admitted to the hospital with a broken leg, P. scraped her ankle on her hospital roommate’s walker. Initially, it didn’t seem like anything serious. “The nurse just stuck a bandage on it,” P. explains.

But the open wound refused to close. Instead, it continued to grow until it had eaten its way deeper into the tissue and halfway around her leg. “At a certain point,” P. says, “it had become a real hole.”

A swab test eventually revealed that MRSA had gotten into the wound. Emma P.’s scratch could now mean death as a result of blood poisoning.

Fears of a ‘Post-Antibiotic Era’

These days, standard antibiotics are almost completely ineffective against pathogens like MRSA. And, to make matters worse, pharmaceutical companies don’t even have any new ones in development. Since new antibiotics must be used in moderation so as to slow the emergence of resistant strains, drug makers have few incentives to develop them. Likewise, the World Health Organization (WHO) is already warning that, if we don’t come up with new ways to fight these kinds of infectious diseases, we might just enter into a “post-antibiotic era” in which they can’t be treated at all.

Although this is an admittedly nightmarish scenario, there have been some studies and projects suggesting that these bacteria can be successfully combatted. But, to get there, we have to develop the right strategy.

“First, we have to create an awareness of the problem,” says Petra Gastmeier, who heads the Institute of Hygiene and Environmental Medicine at Berlin’s Charité Hospital. “Otherwise, a doctor who has worked at a hospital for five years will just think the infection level at that hospital is normal.”

For years, regular and thorough hand disinfection has been regarded as a miracle weapon against every type of hospital infection. But this practice is no longer enough by itself. Indeed, the daily hospital routine has become so complex that an ICU nurse caring for three patients would have to wash his or her hands an unfeasible 150 times a day just to have a good chance of preventing the transmission of multiresistant bacteria.

And then there are other issues. As Matthias Schrappe, director of the University of Bonn’s Institute for Patient Safety, explains, “multiresistant bacteria are also transmitted outside the hospital and brought back into the clinical setting from there. Anyone who hopes to successfully combat these pathogens has to take this into account.”

Holland’s ‘Search and Destroy’ Technique

Holland’s “search and destroy” strategy for specifically fighting MRSA bacteria has precisely this in mind. Every at-risk patient — for example, anyone who has recently been in a hospital — is first placed in quarantine until the results of a nasal swab test indicate that he or she is MRSA-free. Those found carrying the dangerous bacterium, on the other hand, are kept in isolation and treated until the pathogen can no longer be detected.

Emma P. was also quarantined as soon as she tested positive for the bacterium. “I was allowed to have visitors,” she says, “but they all had to wear masks.” And, she adds, most of the time she was alone, “without a soul in sight.”

As P. explains, her recovery was not a pleasant one. Every day, her wound would undergo a cleaning that involved scraping it out with a sharp-edged spoon and using a vacuum dressing to draw out the fluids in her wound. Every day, an ointment containing one of the last few antibiotics to be effective against MRSA was applied inside her nose, where the bacteria tend to accumulate. And, every day, she had to wash her body and her hair with disinfectant soap.

Still, the effort paid off. After a long three weeks, the MRSA pathogen could no longer be found in P.’s wound. Doctors then removed a piece of skin from her upper leg and grafted it onto the gaping hole in her lower leg. Now the wound is starting to heal.

‘Our Only Chance’

“Actively searching for the bacteria and then targeting and destroying them is our only chance,” says Alexander Friedrich, a senior physician at the Institute for Hygiene at UKM hospital in Münster, Germany. Friedrich believes that the search-and-destroy strategy used in the Netherlands should serve as a model for others. With it, the Dutch have managed to keep their MRSA rates extremely low over the last two decades. 

Five years ago, Friedrich launched EurSafety Health-Net, a joint German-Dutch project that fosters close cooperation in fighting the hospital bacteria between regions along and on both sides of the border. Though the collaboration project might teach the Germans a lot, it could also benefit the Dutch. Ron Hendrix, a microbiologist and project coordinator, lives in Enschede, five kilometers (three miles) from the German border and knows what such proximity can mean. “When there’s a fire in Germany,” he says, “we also have a problem.”

Across the border, in the northwestern German region participating in the project, all hospitals are now required to screen at-risk patients for MRSA. As a result, it is only now possible to get a detailed view of what happens when the medical community tries to sweep a problem under the rug for too long. “Here,” says Friedrich, pointing to a map of the region. “In 2004, two patients with an MRSA strain that was new to the region were transferred from southern Germany to here.” By 2008, he recounts, the same strain of the bacterium was found in hospitals in five different regional districts. It had become uncontrollable — but it halted at the Dutch border.

“Here in Germany, patients are often transferred from one hospital to another,” Friedrich explains. “It was only after we began to closely examine this transfer network that we could finally grasp that all hospitals in the German part of the project region actually make up a more-or-less single entity.”

In addition to hospitals, Friedrich has also brought into his network nursing homes, rehabilitation clinics and, most importantly, the offices of physicians in private practice. “The whole thing can only work,” Friedrich explains, “if they continue to perform swab tests in patients after they have been treated for MRSA in the hospital and to complete the treatment that was started there.”

The Hygiene Officer

Friedrich can already report the new strategy’s initial successes. In the project region surrounding Münster, there has been a sharp drop in the number of cases of MRSA-related blood poisoning. Now, he says, the important thing is to transfer responsibility for fighting MRSA from the level of coordinators and public health departments to deep within the hospitals themselves.

“For example,” Friedrich says, “the public health departments need to occasionally send people to the hospitals to check on whether they really have a hygiene officer, whether this person isn’t also the mobile-phone, radiation and genetic-engineering manager who is also standing in the operating room from morning to night, and whether the only reason he was even appointed as the hygiene officer was because he didn’t say ‘no’ fast enough.”

Ulrich Hartenauer is the chief of anesthesiology at Münster’s EVK hospital — and the perfect example of a hygiene officer who takes his job seriously. “As the chief of anesthesiology,” he says, “I play an important role. Anyone who falls out of my good graces is going to have a rough time. I can quickly make them aware of just how limited their options are.”

To provide hospitals with incentives and a structure for implementing a successful strategy against multiresistant bacteria, Friedrich has created five seals of quality that hospitals can earn in the same way that hotels can earn one to five stars.

The first (and lowest) seal, which is awarded for instituting thorough MRSA-screening processes, is already hanging in the lobby of Hartenauer’s hospital. Now he is doing what he needs to do to earn the second seal: expanding its screening for ESBL-producing pathogens. (The three other seals — for the training of hygiene personnel, the follow-up treatment of infected patients and the development of care networks — will only start being awarded over the next five years.)

A Different Bacteria, a Different Beast

Unfortunately, earning that second seal will be much harder than the first. “It’s now becoming clear,” says Wolfgang Witte, a division head at the Robert Koch Institute, “that the measures taken against MRSA cannot prevent the occurrence of ESBL-producing bacteria.”

Unlike MRSA, ESBL-producing bacteria do not form colonies in the nose and on the skin, but deeper within the body. And when they are in the intestine, for example, they become practically beyond the reach of doctors. What’s more, a wider range of bacteria might be involved, and ones that can pass resistance genes among themselves.

As Witte warns, it’s “critical that we start doing something about ESBL-forming bacteria.” The most important measure will be changing the way antibiotics are used in hospitals so as to make it harder for bacteria to develop resistance to them.

Breaking Old Habits

For his part, Hartenauer is already attending a seminar called “Antibiotic Stewardship” to learn how to advise all the doctors in his hospital on how to use antibiotics in a more logical way. But many more people need to follow suit. “There are far too few experts in this field,” says Winfried Kern, head of the Center of Infectious Diseases and Travel Medicine at the University of Freiburg in the southern German city, who launched the seminar. “Doctors just keep using antibiotics in the same way they were first taught to.”

According to Hartenauer, a typical thing he needs to educate doctors about is “perioperative antibiotic prophylaxis.” The surgical practice is used to make sure that all skin bacteria entering a surgical wound are immediately killed off. “But surgeons have a different way of thinking about it,” Hartenauer says. “They say to themselves: ‘Hmm, this was a difficult operation. I removed necrotic tissue, and it took a long time. I don’t want this wound to get infected later on. So let’s just extend the prophylaxis by three days.’ Then, of course, I have to get involved and say: ‘We don’t do this anymore.'”

Still, Hartenauer knows he is fighting an uphill battle. “When it comes to antibiotic therapy, I’m interfering directly with the treatment prerogatives of a fellow physician,” he says. “That’s when I might find myself resorting to psychological tricks.”

Getting hospital management on his side can also be helpful, Hartenauer adds: “I tell them: ‘I’ll help you reduce your annual budget for antibiotics by €20,000 ($28,000).'”


Full article and photos: http://www.spiegel.de/international/germany/0,1518,726781,00.html