March 11, 2008
Cases Without Borders
Psychotherapy for All: An Experiment
By DAVID KOHN
SIOLIM, India — At the faded one-story medical clinic in this fishing and farming village, people with depression and anxiety typically got little or no attention. Busy doctors and nurses focused on physical ailments — children with diarrhea, laborers with injuries, old people with heart trouble. Patients, fearful of the stigma connected to mental illness, were reluctant to bring up emotional problems.
Last year, two new workers arrived. Their sole task was to identify and treat patients suffering depression and anxiety. The workers found themselves busy. Almost every day, several new patients appeared. Depressed and anxious people now make up “a sizable crowd” at the clinic, said the doctor in charge, Anil Umraskar.
The patients talk about all sorts of troubles. “Financial difficulties are there,” said one of the new counselors, Medha Upadhye, 29. “Interpersonal conflicts are there. Unemployment. Alcoholism is a major problem.”
The clinic is at the forefront of a program that has the potential to transform mental health treatment in the developing world. Instead of doctors, the program trains laypeople to identify and treat depression and anxiety and sends them to six community health clinics in Goa, in western India.
Depression and anxiety have long been seen as Western afflictions, diseases of the affluent. But new studies find that they are just as common in poor countries, with rates up to 20 percent in a given year.
Researchers say that even in places with very poor people, the ailments require urgent attention. Severe depression can be as disabling as physical diseases like malaria, the researchers say, and can have serious economic effects. If a subsistence farmer is so depressed that he cannot get out of bed, neither he nor his children are likely to eat.
In India, as in much of the developing world, depression and anxiety are rarely diagnosed or treated. With a population of more than one billion, India has fewer than 4,000 psychiatrists, one-tenth the United States total. Because most psychiatrists are clustered in a few urban areas, the problem is much worse elsewhere.
As a result, most Indians with mental illness go untreated, especially in poor and rural areas. “There is a huge treatment gap for people with depression,” said Dr. Vikram Patel of the London School of Hygiene and Tropical Medicine, the psychiatrist who began the Siolim project. “In most places in the developing world, 80 percent to 90 percent of people with severe depression don’t receive adequate treatment.”
For India, adding thousands of psychiatrists would take large sums of money and years of effort, resources unavailable to a developing country with many other health problems besides mental illness. By contrast, Dr. Patel’s strategy costs relatively little and does not require legions of doctors.
“It’s a really interesting, exciting thing he’s doing,” said Dr. Greg E. Simon, a researcher at the Center for Health Studies in Seattle.
Dr. Simon, a psychiatrist who studies mental health in the developing world, said the Goa strategy grew from a crucial idea. Unlike, say, heart disease and stroke, which can require expensive interventions, depression is relatively simple to diagnose and treat. Many studies have shown that talk therapy and antidepressants lead to significant improvement in most patients.
“The fundamentals of helping people with depression are pretty low tech,” Dr. Simon said. “The core resource is humans,” people who can identify patients and offer treatments.
The Goa program, financed by the Wellcome Trust, is not the first using nonmedical workers to treat mental illness, but it is the largest. Almost 2,000 patients have been treated. Dr. Patel is conducting a randomized clinical trial to see whether the strategy works, the first time such a careful study has been run in the developing world.
If the research, which will finish in 2010, reports positive results, donors and governments are more likely to try it elsewhere in India and the world, Dr. Patel said, adding: “This is the most important question in psychiatry. How do we scale up treatments to a population in a low-resource setting?”
“If you rolled this program out across India,” Dr. Simon said, “you’d be doing some good for a fifth of the world’s population.”
Dr. Patel, 43, grew up in Bombay, now Mumbai, and wanted to be a caterer. His middle-class parents insisted on a more respectable career. He went to medical school.
After completing training, he spent two years in Zimbabwe as a researcher. He hoped to prove that Western concepts of mental illness did not apply in the developing world. Instead, he came to the opposite conclusion, that the ailments were in fact just as common and just as treatable as in the West.
He now splits his time between London and Goa, where he runs a social welfare organization, Sangath, which means partnership in Hindi.
Known in the West for its beautiful beaches, Goa is relatively wealthy by Indian standards. But most of its three million residents earn a few dollars a day, not enough to afford much medical care. Public health officials say that poverty can lead to alcoholism, domestic abuse and stress, all contributors to depression and anxiety.
At government clinics like the one here, overworked doctors lack time and inclination to ask patients about mental health. Even clinicians who look for depression may miss it. For reasons that no one fully understands, depressed patients in the developing world often complain of physical symptoms like fatigue, headache and insomnia rather than emotional problems like sadness or regret.
As a result, Dr. Patel said, depressed patients in Goa may receive unnecessary and expensive treatments that fail to address the underlying problem. For all those reasons, he said, most depression and anxiety remains undiagnosed. But they are common. A survey by Dr. Patel found that one in three adults seeking care at public health clinics in Goa were depressed or anxious. Dr. Neerja Chowdhury, a psychiatrist at Sangath who is helping manage the project, said, “That might be an underrepresentation.”
The program began in 2005, hiring 12 recent high school or college graduates who lacked medical backgrounds. Six “health assistants” received a week of training, and six “health counselors” had three months of training. The workers — paid the equivalent of $100 to $200 a month, significantly less than Indian psychiatrists — were sent to the six clinics.
Five days a week, the assistants screen almost every patient who arrives at the door. Pregnant women, minors and emergency cases are excluded. The screening is created for the program. It includes questions about physical symptoms, as well as emotional problems.
A patient meeting the criteria for mental illness is immediately sent to the health counselor, who provides a straightforward explanation of depression and anxiety and offers a range of treatments like talk therapy, yoga and, in conjunction with a doctor, antidepressant medication. Patients return every few weeks for follow-ups.
The screening and first consultation typically take a half-hour. In the old system, the few patients with diagnoses of depression were referred to a psychiatrist at one of two state mental hospitals. Dr. Patel said many patients failed to show up for appointments because they could not afford to take time from work or pay for transportation.
Most are also apparently wary of visiting a mental hospital. In India, the stigma of mental illness remains strong. To minimize the problem, health workers avoid using the words “mental illness,” “depression” or “anxiety” with patients, relying on more commonly used words like “strain” and “tension.”
The patients “are happy to talk,” Dr. Sudipto Chatterjee, a psychiatrist at Sangath, said, “as long as you stay away from the idea of mental illness.”
Dr. Chatterjee helped draw up the program and oversees the screeners and counselors. He said they not only diagnosed as well as doctors but were generally better listeners, partly because they have more time.
Psychiatrists usually “have five minutes to see a patient,” Dr. Chatterjee said.
In a society where many people have no place to share their worries, the effects of therapy can be striking. On a recent Saturday morning at the Siolim clinic, Ms. Upadhye, the health counselor, sat in her closet-size plywood-wall office, trying to stay cool under a negligible breeze from a tiny plastic fan, when a psychiatric patient arrived for a return visit.
A housemaid in her 50s who wore large glasses, bright bangles on her wrists and a light blue sari, the patient had originally reported physical problems like headache, insomnia and pains but had been given a diagnosis of depression. As Ms. Upadhye listened, the woman let loose a flood of words.
Speaking in Konkani, the predominant Goan language, she told the counselor that she was not getting along with her four children, especially her son, who had recently beaten her up in a drunken rage. She said she had no one to talk to. Holding tightly to her handkerchief, she began to cry.
Within minutes, she began to relax. Her expression loosened.
“I feel better when I tell my problems to somebody else,” she said.
Ms. Upadhye ended by reminding the woman to keep taking her antidepressant medicine and to check in regularly.
After the session, Ms. Upadhye reflected that just listening to her patients made a big difference.
“I feel like I’m doing something, just giving them time to ventilate,” she said. “They can tell their problems, they can share their feelings.”
March 11, 2008
Uganda: Vaccine Program Vanquishes a Dangerous Type of Childhood Meningitis
By DONALD G. McNEIL Jr.
A dangerous type of childhood meningitis has been virtually eliminated in Uganda in just five years after a vaccine was introduced, according to a study released this week.
That should save the lives of 5,000 children a year, the authors estimated.
“This is the first time we’ve seen this kind of impact, a 100 percent drop,” said Dr. Julian Lob-Levyt, executive secretary of the GAVI Alliance, which paid for the vaccines. “We hope this can be repeated in other countries.”
The study, released by the World Health Organization, monitored cases from 2001 to 2006.
The vaccine, known as Hib, protects against haemophilus influenzae type B, a bacterium that can inflame the lining of the brain or cause pneumonia. Each year, it kills 386,000 children globally. Three million more have severe side effects like deafness, paralysis or retardation.
The vaccine has existed since 1991 but was rare in the third world until the creation of the alliance — originally the Global Alliance for Vaccines and Immunization — in 2000. Even at prices offered to poor countries, it had cost $7 , seven times as much as other vaccines.
The alliance joins United Nations health agencies, the World Bank, vaccine companies, universities and the Bill & Melinda Gates Foundation, and receives money from $1 billion in bonds issued by the International Finance Facility for Immunization.
By guaranteeing large orders, the alliance tries to drive down the price of vaccines. It estimates that it has helped prevent 2.3 million early deaths since 2000.
In wealthy countries, Hib vaccine is typically given at the age of 8 weeks.
April 24, 2008
To Screen or Not for Lung Cancer: Does It Make a Difference?
By PHILIP M. BOFFEY
For as long as I can remember, a diagnosis of lung cancer has been virtually a death sentence. Most victims die within a year or two, and some 95 percent ultimately succumb to the disease. So it is hard not to be intrigued by a bold claim that most lung cancers could be cured through a screening program to detect tumors early and remove them promptly.
That claim has set off a bitter battle in scientific journals and forums that emerges occasionally into public view. Egos and personalities have clashed, derogatory comments have been muttered and conflict-of-interest charges have been flung at opposing scientists.
In one camp are researchers at Weill Cornell Medical College, who are convinced that screening asymptomatic smokers and former smokers with spiral CT scans — far more sensitive than conventional chest X-rays — could prevent some 80 percent of the 160,000 annual deaths from lung cancer in this country. That would be an astonishing feat, almost too good to believe.
In the other camp are distinguished experts in cancer and screening technologies who believe that the amazing claims will turn out to be greatly exaggerated, if not a complete mirage. They fear a repeat of a previous fiasco in which the medical profession latched onto chest X-rays as a way to detect and treat lung cancer early only to find out, when controlled studies were later performed, that the screening failed to reduce lung cancer mortality.
The core disagreement is over what to make of a large, multicenter study of spiral CT screening led by the Weill Cornell team. The researchers screened some 35,000 people with a history of smoking or occupational exposure. It was determined that 484 of them had lung cancer, and most of the tumors were surgically removed. They estimated that 92 percent of those who had early-stage tumors that were promptly removed would be alive 10 years later, a stunning survival rate compared with the roughly 10 percent who survive 10 years after diagnosis in current practice. All eight people with early-stage cancers who chose not to remove them died within five years.
That may sound like a slam-dunk case for spiral CT screening, but it isn’t. The researchers lacked a control group of people who did not get CT scans to compare with those who did. Thus they have no definitive proof that people who are screened die less frequently of lung cancer than those not screened.
This is not trivial. A contrasting study published last year underscored how misleading — and dangerous — it could be to assume that increasing the number of people who survive five or 10 years after diagnosis means that anyone’s life has been saved or lengthened.
The study analyzed the effects of CT screening in some 3,000 patients at three medical centers. Screening greatly increased the number of small tumors found and the number of surgeries to remove them, but it did not reduce the number of lung cancer deaths, which was the goal of the whole process. A plausible explanation is that a lot of the tumors would not have killed people even if left alone, while the truly lethal tumors were not caught in time.
Meanwhile, the screening itself led to follow-up scans, invasive biopsies and lung surgeries that caused sickness and death. That could be a huge problem in any large-scale program. In run-of-the-mill medical care in this country, lung cancer surgery kills 4 to 5 percent of patients and inflicts serious complications on many more. Those risks may not be worth taking if the benefit is small.
The best hope for an answer to the screening puzzle lies with a large federal trial of 50,000 current and former smokers that is comparing spiral CT screening with standard chest X-rays to see which saves more lives. The National Cancer Institute needs to do everything possible to expedite the researchers’ analysis of their data. The usual pokey pace of academic research seems inadequate when many thousands of lives could be at stake.
At this point, in the absence of firm evidence that CT screening is beneficial, no major medical organization recommends its widespread use. On an individual level, any heavy smoker who might want to get screened should recognize that there can be harms as well as benefits. The scans are so sensitive that they pick up lots of things not worth worrying about, yet once something is detected it is hard to resist the urge to do follow-up procedures. Any screening is best done by doctors sophisticated enough to recognize and treat only what really needs treatment.
Duchenne muscular dystrophy may not seem to have much in common with heart attacks. One is a rare inherited disease that primarily strikes boys. The other is a common cause of death in both men and women. To Atul J. Butte, they are surprisingly similar.
Dr. Butte, an assistant professor of medicine at Stanford, is among a growing band of researchers trying to redefine how diseases are classified — by looking not at their symptoms or physiological measurements, but at their genetic underpinnings. It turns out that a similar set of genes is active in boys with Duchenne and adults who have heart attacks.
The research is already starting to change nosology, as the field of disease classification is known. Seemingly dissimilar diseases are being lumped together. What were thought to be single diseases are being split into separate ailments. Just as they once mapped the human genome, scientists are trying to map the “diseasome,” the collection of all diseases and the genes associated with them.
“We are now in a unique position in the history of medicine to define human disease precisely, uniquely and unequivocally,” three scientists wrote of the new approach last year in the journal Molecular Systems Biology. Such research aims to do more than just satisfy some basic intellectual urge to organize and categorize. It also promises to improve treatments and public health.
Scientists are finding that two tumors that arise in the same part of the body and look the same on a pathologist’s slide might be quite different in terms of what is occurring at the gene and protein level. Certain breast cancers are already being treated differently from others because of genetic markers like estrogen receptor and Her2, and also more complicated patterns of genetic activity.
“In the not too distant future, we will think about these diseases based on the molecular pathways that are aberrant, rather than the anatomical origin of the tumor,” said Dr. Todd Golub, director of the cancer program at the Broad Institute in Cambridge, Mass.
The reclassification may also help find drugs. “There are 40 drugs to treat heart attacks, but none to treat muscular dystrophy,” Dr. Butte said. If the diseases are similar in some molecular pathways, perhaps the heart attack drugs should be tested against muscular dystrophy.
Dr. Golub and colleagues at the Broad Institute have developed a “Connectivity Map,” which profiles drugs by the genes they activate as a way to find new uses for existing drugs.
The research will also improve understanding of the causes of disease and of the functions of particular genes. For instance, two genes have recently been found to influence the risk of both diabetes and prostate cancer.
“I’m shaking my head with disbelief that two genes would pop up in these two diseases that have absolutely nothing in common,” said Dr. Francis S. Collins, the director of the National Human Genome Research Institute. He said another gene, cyclin-dependent kinase inhibitor 2A, seemed to be involved in cancer, diabetes and heart disease.
A consistent way to classify diseases is also essential for tracking public health and detecting epidemics. The World Health Organization takes pains to periodically revise its International Classification of Diseases, which is used, among other ways, to tally the causes of death throughout the world. The classification is also the basis of the ICD-9 codes used for medical billing in the United States.
The first international classification, in the 1850s, had about 140 categories of disease, according to Dr. Christopher G. Chute, chairman of biomedical informatics at the Mayo Clinic. The 10th edition, in 1993, had 12,000 categories, said Dr. Chute, chairman of the committee developing the 11th version, due in 2015.
The increase stems mainly from better knowledge and diagnostic techniques that allow diseases to be distinguished from one another. For most of human history, diseases were named and classified by symptoms, which was all people could observe.
Linnaeus, the 18th-century Swedish scientist known for categorizing creatures into genus and species, also developed a taxonomy of disease. He had 11 classes — painful disease, motor diseases, blemishes and so on — that were further broken down into orders and species. But not knowing about viruses, for instance, he classified rabies as a mental disease, Dr. Chute said.
In the 19th century, a big shift occurred. Doctors began learning how to peer inside the body. And diseases began to be classified by their anatomic or physiological features.
The stethoscope let doctors realize that what had been thought of as 17 conditions — like coughing up blood and shortness of breath — could all be different symptoms of the same disease, tuberculosis.
“The advent of the stethoscope made it possible to unify tuberculosis,” said Dr. Jacalyn Duffin, a professor of the history of medicine at Queen's University in Ontario.
The shift from symptoms to anatomical measurements had big implications for patients, said Dr. Duffin, who is also a hematologist.
“Up until the 18th century, you had to feel sick to be sick,” she said. But now people can be considered sick based on measurements like high blood pressure without feeling ill at all.
Indeed, Dr. Duffin said, people who feel sick nowadays “don’t get to have a disease unless the doctor can find something” and instead might be told that it’s all in their head. Doctors argue, for instance, about whether fibromyalgia or chronic fatigue syndrome, which have no obvious anatomical causes, are really diseases.
Genes might allow the study of diseases at a finer level than even physiological tests. Genes are the instructions for the production of proteins, which interact in complex ways to carry out functions in the body. Disruptions in these molecular pathways can cause disease.
“It gives you a direct connection to what the root causes are,” said Dr. David Altshuler, a professor of medicine and genetics at Harvard and Massachusetts General Hospital, and a researcher at the Broad Institute. “That is different from listening to a stethoscope.”
Some of the earliest work has until now been with inherited diseases caused by mutations in a single gene. Diseases have been subdivided by the type of mutation. Hemophilia was divided into hemophilia A and B, caused by mutations in different genes for different clotting factors. And what was once considered a mild form of hemophilia was later identified as a variant of a different clotting disorder, von Willebrand disease, caused by mutations in a different gene and requiring a different clotting factor as treatment.
Diseases are being lumped, as well as split. Researchers at Johns Hopkins reported in the April issue of Nature Genetics that two rare syndromes with different symptoms might represent a continuum of one disease. One syndrome, Meckel-Gruber, is tied to neural defects and death in babies. The other, Bardet-Biedl, is marked by vision loss, obesity, diabetes and extra fingers and toes.
The techniques are being applied to diseases for which the genetic cause is not as clearly known and which might be a result of multiple genes.
Dr. Butte uses data from gene chips that measure which genes are active, or expressed, in a cell. Amid thousands of studies using such chips, many compared the gene activity patterns in diseased tissue with that of healthy tissue.
Much of the raw data from such studies are deposited in a database. So Dr. Butte can gather data on gene activity for scores of diseases without leaving his desk. He then performs statistical analyses to map diseases based on similarities in their patterns of gene activity.
Other scientists use data on which genes appear to cause disease or contribute to the risk of contracting it.
Using such data, Marc Vidal, a biologist at Harvard, and Albert-Laszlo Barabasi, now a physicist at Northeastern University, created a map of what they called the “diseasome” that was published last year in The Proceedings of the National Academy of Sciences.
Diseases were represented by circles, or nodes, and linked to other diseases by lines that represent genes they have in common — something like the charts linking actors to one another (and ultimately to Kevin Bacon) based on the movies they appeared in together.
The number of genes associated with diseases is expanding rapidly because of so-called whole genome association studies. In these studies, gene chips are used to look for differences between the genomes of people with a disease and those without.
Multiple techniques can be combined. In a paper published online in Nature in March, scientists at Merck reconstructed the network of genes involved in obesity.
One area that might benefit from genetic disease classification is psychiatry. Because of the difficulty of measuring the brain, psychiatric diagnoses are still mainly based on symptoms. The Diagnostic and Statistical Manual of Mental Disorders contains descriptions of conditions as diverse as acute stress disorder and voyeurism.
Scientists have found that certain genes appear to be associated with both schizophrenia and bipolar disorder. Those links, and the fact that some drugs work for both diseases, have prompted a debate over whether they are truly distinct disorders. “The way we categorize these into two separate entities is almost certainly not correct,” said Dr. Wade H. Berrettini, a professor of psychiatry at the University of Pennsylvania.
But Dr. Kenneth S. Kendler, a professor of psychiatry and human genetics at Virginia Commonwealth University, said that even if the two diseases shared genes, the diseases remained distinct. Schizophrenia is marked by hallucinations and impaired social functioning, and bipolar disorder by mood swings.
“It’s extremely naïve to think that psychiatric illnesses will collapse into categories defined by a gene,” he said. “Each gene at most has a quite modest effect on the illness.”
Some experts say that such limitations may hold true for other diseases, as well, and that genetics will not be able to unequivocally define and distinguish diseases. “We shouldn’t expect, nor will we get, this decisive clarity,” said Fiona A. Miller, associate professor of health policy, management and evaluation at the University of Toronto.
She and others said genetic classification could bring its own ambiguities. Newborns are now often screened for cystic fibrosis with the idea that they can be treated early to help avoid complications. But some infants with a mutation in the gene responsible for the disease are unlikely ever to have symptoms. Do they have the disease?
“We don’t know what to call these infants,” said Dr. Frank J. Accurso, a professor of pediatrics at the University of Colorado. “We don’t even have a good language for it yet.”
Still, Dr. Butte said nosology based on genes would one day make today’s classifications look as quaint as ones from 100 years ago look now. One category in the 1909 listing of the causes of death, for instance, was “visitation of God.”
“Imagine how they are going to be laughing at us,” he said. “Not 100 years from now, but even 50 or 20 years from now.”
Apart from its sadness, Tim Russert’s death this month at 58 was deeply unsettling to many people who, like him, had been earnestly following their doctors’ advice on drugs, diet and exercise in hopes of avoiding a heart attack.
Mr. Russert, the moderator of “Meet the Press” on NBC News, took blood pressure and cholesterol pills and aspirin, rode an exercise bike, had yearly stress tests and other exams and was dutifully trying to lose weight. But he died of a heart attack anyway.
An article in The New York Times last week about his medical care led to e-mail from dozens of readers insisting that something must have been missed, that if only he had been given this test or that, his doctors would have realized how sick he was and prescribed more medicine or recommended bypass surgery.
Clearly, there was sorrow for Mr. Russert’s passing, but also nervous indignation. Many people are in the same boat he was in, struggling with weight, blood pressure and other risk factors — 16 million Americans have coronary artery disease — and his death threatened the collective sense of well-being. People are not supposed to die this way anymore, especially not smart, well-educated professionals under the care of doctors.
Mr. Russert’s fate underlines some painful truths. A doctor’s care is not a protective bubble, and cardiology is not the exact science that many people wish it to be. A person’s risk of a heart attack can only be estimated, and although drugs, diet and exercise may lower that risk, they cannot eliminate it entirely. True, the death rate from heart disease has declined, but it is still the leading cause of death in the United States, killing 650,000 people a year. About 300,000 die suddenly, and about half, like Mr. Russert, have no symptoms.
Cardiologists say that although they can identify people who have heart disease or risk factors for it, they are not so good at figuring out which are in real danger of having an attack soon, say in the next year or so. If those patients could be pinpointed, doctors say, they would feel justified in treating them aggressively with drugs and, possibly, surgery.
“It’s the real dilemma we have in cardiology today,” said Dr. Sidney Smith, a professor of medicine at the University of North Carolina and a past president of the American Heart Association. “Is it possible to identify the group at higher short-term risk?”
What killed Mr. Russert was a plaque rupture. A fatty, pimplelike lesion in a coronary artery burst, and a blood clot formed that closed the vessel and cut off circulation to part of the heart muscle. It was a typical heart attack, or myocardial infarction, an event that occurs 1.2 million times a year in the United States, killing 456,000 people.
In Mr. Russert’s case, the heart attack led to a second catastrophe, an abnormal heart rhythm that caused cardiac arrest and quickly killed him. An electric shock from a defibrillator might have restarted his heart if it had been given promptly when he collapsed at his desk. But it was apparently delayed.
Dr. Smith and other cardiologists say the main problem is that there is no way to figure out who has “vulnerable plaques,” those prone to rupture. Researchers are trying to find biomarkers, substances in the blood that can show the presence of these dangerous, ticking time-bomb plaques. So far, no biomarker has proved very accurate.
Mr. Russert’s heart disease was a mixed picture. Some factors looked favorable. There was no family history of heart attacks. Though he had high blood pressure, drugs lowered it pretty well, said his internist, Dr. Michael A. Newman. His total cholesterol was not high, nor was his LDL, the bad type of cholesterol, or his C-reactive protein, a measure of inflammation that is thought to contribute to plaque rupture. He did not smoke. At his last physical, in April, he passed a stress test, and his heart function was good. Dr. Newman estimated his risk of a heart attack in the next 10 years at 5 percent, based on a widely used calculator.
On the negative side, Mr. Russert had low HDL, the protective cholesterol, and high triglycerides. He was quite overweight; a waist more than 40 inches in men increases heart risk. A CT scan of his coronary arteries in 1998 gave a calcium score of 210, indicating artery disease — healthy arteries do not have calcium deposits — and a moderate to high risk of a heart attack. An echocardiogram in April found that the main heart pumping chamber had thickened, his ability to exercise had decreased slightly, and his blood pressure had increased a bit. Dr. Newman and his cardiologist, Dr. George Bren, changed his blood pressure medicines, and the pressure lowered to 120/80, Dr. Newman said.
Another blood test, for a substance called apoB, might have been a better measure of risk than LDL, some doctors say. Others disagree.
Some doctors say people like Mr. Russert, with no symptoms but risk factors like a thickened heart, should have angiograms, in which a catheter is threaded into the coronary arteries, dye is injected, and X-rays are taken to look for blockages. Some advocate less invasive CT angiograms. Both types of angiogram can identify plaque deposits, and if extensive disease or blockages at critical points are found, a bypass is usually recommended. But the tests still cannot tell if plaques are likely to rupture, Dr. Smith and other cardiologists say. And Mr. Russert’s doctors did not think that an angiogram was needed.
An autopsy found, in addition to the plaque rupture, extensive disease in Mr. Russert’s coronary arteries, enough to surprise his doctors, they said. Had they found it before, Dr Newman said, a bypass would have been recommended. Dr. Bren differed, saying many cardiologists would still not have advised surgery.
Given all the uncertainties, what’s a patient to do?
“You want to be sure your blood pressure and lipids are controlled, that you’re not smoking, and you have the right waist circumference,” Dr. Smith said.
Statins can reduce the risk of dying from a heart attack by 30 percent, he said.
“But what about the other 70 percent?” Dr. Smith asked. “There are other things we need to understand. There’s tremendous promise, but miles to go before we sleep.”
Do Women Handle Stress Better Than Men?
by Tina Coleman
As most couples are aware, men and women respond differently to stress. What hasn't been clear until now is how or why. Our understanding of the human stress response has been based on the "fight-or-flight" model, which states that when confronted with a stressful situation, humans either will respond with aggressive behavior or will withdraw.
What About the Women?
Studies of stress response conducted prior to 1995 corroborated the "fight-or-flight" theory. These studies focused heavily on male subjects because researchers believed that a woman's monthly hormonal fluctuations created stress responses that were too varied to be statistically valid. But in 1995, the federal government mandated representation of both men and women in agency-funded studies. As a result, the percentage of female subjects participating in stress research increased.
Studying Women Reveals a Different Stress Response
A study at the University of California, Los Angeles (UCLA) published in the July 2000 issue of Psychological Review offers clues to the biological and behavioral differences in the ways men and women cope with stress. The study found that females of many species, including humans, respond to stressful situations by protecting and nurturing their young and by seeking social contact and support from others, particularly females. The study refers to this response as "tend-and-befriend."
Researchers believe this response is a result of natural selection.
"Thousands of generations ago, fleeing or fighting in stressful situations was not a good option for a female who was pregnant or taking care of offspring, and women who developed and maintained social alliances were better able to care for multiple offspring in stressful times," says the study's principal investigator Shelley E. Taylor.
Biology May Favor Females
As with the fight-or-flight response common in males, this tend-and-befriend response to stress may have a biological basis. The hormone oxytocin, which is secreted by both males and females in response to stress, is believed to play a role.
"Animals and people with high levels of oxytocin are calmer, more relaxed, more social, and less anxious," says Taylor. In males, the effects of oxytocin seem to be reduced by male hormones, but in females, she says, oxytocin—along with other stress hormones—may play a key factor in reducing the female response to stress.
Men are more likely than women to respond to stressful experiences by developing certain stress-related disorders, including hypertension , aggressive behavior, or abuse of alcohol , or hard drugs, Taylor says, while the tend-and-befriend response may protect women against stress.
But in Some Circumstances, Women Are At Higher Risk
Doctors have recognized a condition that they have memorably called “broken heart syndrome.” In this probably rare condition, acute stress such as news of a loved one’s death leads to sudden onset of chest pain, heart failure , or even sudden death. While broken heart syndrome does occur in men, 95% of the persons studied in a February 2005 New England Journal of Medicine study on this syndome were women.
Broken heart syndrome reflects the important connection between our brain and our heart. In this case the stress hormone responses work against women, making them more susceptible to serious consequences of extreme stress. Notably, two of the women reported with broken heart syndrome in the New England Journal of Medicine study developed symptoms after strong pleasant surprises. It is likely that even sudden good stress can lead to bad outcomes in susceptible persons. At present we don’t really know how to predict broken heart syndrome, although it has been reported most commonly in women over age 45.
What Do You Do When You're Stressed?
In a study prepared for the Assistant Secretary of Defense by the Research Triangle Institute in 1998, researchers looked into the mental health effects of stress on active-duty military personnel. The study found that more men (24.6%) than women (15.5%) reported using alcohol as a coping behavior. Women were more likely than men to talk to a friend or family member (87.1% versus 70.8%, respectively). Men were found to be more likely to light up a cigarette, while women were more likely to pray. Women were also more likely to eat in response to stress, while men were more likely to turn to illegal drugs.
The results of the UCLA study may help explain such things as why men are reluctant to ask for directions when lost, why men are more vulnerable to the adverse health effects of stress, and why women enjoy a significantly longer life expectancy than men do.
What Does This Mean for You and Your Better Half?
"For men it would suggest that reaching out is beneficial—protective, even—in times of stress," says Richard Driscoll, PhD, author of The Stronger Sex . "But for hundreds of thousands of years, men who revealed their weaknesses tended to be undesirable mates. Hiding weaknesses has been biologically advantageous, and men still tend to be less likely to reveal weaknesses."
This reluctance on the part of men to reach out, Dr. Driscoll believes, could help explain the difference in life expectancy between the genders.
"Women get more medical care; they consume two out of three healthcare dollars. They are more likely to seek help from therapists. Men don't get the healthcare; they tend not to reach out."
Help for Men
"Men have very strong tendencies to conceal stressful things," Dr. Driscoll adds. But our society is designed that way. Crying is still not acceptable in men, he points out. "We have to have a softer, gentler, more sympathetic approach to men, particularly those who aren't at the top of their game," says Dr. Driscoll. We need to acknowledge to young sons the particular difficulties that they will face being a boy and a man in an unsympathetic world, he explains.
Men need to learn to deal with stress in a healthy manner, says Dr. Driscoll. He recommends a process he developed called "mental shielding" to brush off hostility. Mental shielding involves developing the ability to disengage from hostile comments and remain in control, first by achieving a calm, relaxed state, and then creating a mental shield between yourself and your partner. This deflects the hostility and allows you to better deal with the core issues.
In a set of recent focus groups, participants were asked to rank the severity of various health problems, including cancer, heart disease and diabetes.
On a scale of 1 to 10, cancer and heart disease consistently ranked as 9s and 10s. But diabetes scored only 4s and 5s.
“The general consensus seems to be, ‘There’s medication,’ ‘Look how good people look with diabetes’ or ‘I’ve never heard of anybody dying of diabetes,’ ” said Larry Hausner, chief executive of the American Diabetes Association, which held the focus groups. “There was so little understanding about everything that dealt with diabetes.”
But diabetes is anything but minor. It wreaks havoc on the entire body, affecting everything from hearing and vision to sexual function, mental health and sleep. It is the leading cause of blindness, amputations and kidney failure, and it can triple the risk for heart attack and stroke.
“It is a disease that does have the ability to eat you alive,” said Dr. John B. Buse, a professor at the University of North Carolina School of Medicine who is the diabetes association’s president for medicine and science. “It can be just awful — it’s almost unimaginable how bad it can be.”
Diabetes results when the body cannot use blood sugar as energy, either because it has too little insulin or because it cannot use insulin. Type 2 diabetes, which accounts for 90 to 95 percent of cases, typically develops later in life and is associated with obesity and lack of exercise. Type 1 diabetes, which is often diagnosed in children, occurs when the immune system mistakenly destroys cells that make the insulin.
The disconnect between perception and reality is particularly worrisome at a time when national diabetes rates are surging. Just last week, the Centers for Disease Control and Prevention announced that the number of Americans with diabetes had grown to about 24 million, or 8 percent of the population. Almost 25 percent of those aged 60 and older had diabetes in 2007. And the C.D.C. estimates that 57 million people have abnormal blood sugar levels that qualify as pre-diabetes.
To be sure, diabetes is treatable, and an array of new medications and monitoring tools have dramatically improved the quality of care. But keeping the illness in check requires constant vigilance and expensive care, along with lifestyle changes like losing weight, exercising regularly and watching your carbohydrates.
Dr. Buse says patients who are focused on their disease and who have access to regular medical care have a good chance of living out a normal life span without developing a diabetes-related disability.
But some patients say they are too busy to take better care of themselves, and many low-income patients can’t afford regular care. Even people with health insurance struggle to keep up with the co-payments for frequent doctor visits and multiple medications.
And to make matters worse, diabetes is associated with numerous other health problems. Last week, for example, The Journal of the American Medical Association reported that people with depression were at higher risk for Type 2 diabetes, and vice versa.
That is not surprising: according to data published last year in the journal Diabetes Care, depression tends to interfere with a patient’s self-care, which requires glucose monitoring, medications, dietary changes and exercise.
Ultimately, diabetes can take a toll from head to toe. In the brain, it raises the risk not only for depression but also for sleep problems and stroke. It endangers vision and dental health. This month, The Annals of Internal Medicine is reporting that the disease more than doubles the risk of hearing loss.
Moving down the body, diabetes can lead to liver and kidney disease, along with serious gastrointestinal complications like paralysis of the stomach and loss of bowel control. Last year the journal Diabetes Care reported that in a sample of nearly 3,000 patients with diabetes, 70 percent had nonalcohol fatty liver disease.
Poor circulation and a loss of feeling in the extremities, called neuropathy, can lead to severe ulcers and infections; each year in the United States, there are about 86,000 diabetes-related amputations.
Diabetes can also take a toll on relationships. By some estimates, 50 percent to 80 percent of men with diabetes suffer from erectile dysfunction. Experts say women with diabetes often lose their libidos or suffer from vaginal dryness.
The challenge for doctors is to convince patients that diabetes is a major health threat. For years, the message from the American Diabetes Association has been one of reassurance that the disease is treatable. Now, beginning in 2009, the association plans to reframe its message to better communicate the seriousness of the disease.
“Our communication strategy is going to be that diabetes has deadly consequences, and that the A.D.A. is here to change the future of diabetes,” said Mr. Hausner, a former executive with the Leukemia and Lymphoma Society who came to the association 10 months ago. “It’s the word ‘deadly’ that was the potentially controversial word for the organization. In the past, people said, ‘We don’t want to get anybody scared.’ ”
The new strategy is not a scare tactic, he added. Prevention and hope will still be part of the message.
“It’s not that we don’t want people to have hope,” he said. “We want people to understand this is serious.”
July 6, 2008
The Evidence Gap
Costly Cancer Drug Offers Hope, but Also a Dilemma
By GINA KOLATA and ANDREW POLLACK
It took only an instant for 58-year-old Gailanne Reeh to go from the picture of health to death’s door. By chance, her doctor noticed a lump under her arm during a routine exam. It turned out to be advanced breast cancer.
Soon she was having tests to reveal the extent of the cancer and hearing the grim results.
The surgeon, she recalled, “looked at me and said: ‘This is not a conversation I like to have. But I can’t do anything for you. You can’t be cured. You can’t be treated. All we can do is manage your cancer.’ ” On scans to detect tumors, the doctor told Ms. Reeh, “you light up like a Christmas tree.”
And so, like many others in that situation, Ms. Reeh, the vivacious owner of a staffing agency in Boston, was given bevacizumab, also known as Avastin, a drug that signifies both the hopes and dilemmas of modern medicine.
Looked at one way, Avastin, made by Genentech, is a wonder drug. Approved for patients with advanced lung, colon or breast cancer, it cuts off tumors’ blood supply, an idea that has tantalized science for decades. And despite its price, which can reach $100,000 a year, Avastin has become one of the most popular cancer drugs in the world, with sales last year of about $3.5 billion, $2.3 billion of that in the United States.
But there is another side to Avastin. Studies show the drug prolongs life by only a few months, if that. And some newer studies suggest the drug might be less effective against cancer than the Food and Drug Administration had understood when the agency approved its uses.
While many patients and their doctors say the drug can improve the quality of life — like a sense of well-being and an ability to carry out daily tasks without exhaustion or pain — such effects can be hard to document. Meanwhile, many patients with cancers other than those of the colon, lung or breast are taking the drug, even in cases where there is no compelling evidence that it can help.
Avastin also has serious, if infrequent, side effects, some of which can be lethal. And because it is almost always used with standard chemotherapy — it did not work as well when researchers tried it alone — patients on Avastin do not escape chemotherapy’s side effects.
“I still use Avastin routinely, but it’s sobering,” Dr. Leonard Saltz, a colon cancer specialist at Memorial Sloan-Kettering Cancer Center in New York, said of the new data. “It’s not a slam dunk and, in fact, the incremental benefit may be more modest than we want to admit.”
If Avastin were inexpensive or if it cured cancer or even held it at bay, as the drug Gleevec does for blood cancer, few might care. But like a half-dozen or so new biotechnology drugs with a similar combination — alluring promise, high price and only arguable benefits — Avastin raises troubling questions:
What does it mean to say an expensive drug works? Is slowing the growth of tumors enough if life is not significantly prolonged or improved? How much evidence must there be before billions of dollars are spent on a drug? Who decides? When, if ever, should cost come into the equation?
For a patient like Ms. Reeh, fighting for her life, the cost is not the main concern. If her insurer did not pay, she said, she would go into debt, find a way to raise the money.
But some in the pharmaceutical industry worry that such prices will raise concerns about whether the drugs are worth it, leading to a backlash like price controls or restrictions on use.
Roy Vagelos, a former chief executive of Merck who is considered an elder statesman of the industry, said in a recent speech that he was troubled by a drug, which he would not name but which was a clear reference to Avastin, that costs $50,000 a year and adds four months of life. “There is a shocking disparity between value and price,” he said, “and it’s not sustainable.”
Some patient advocates are also troubled by very expensive treatments like Avastin coming into routine use on what they see as little more than a hope and an expensive prayer.
“It’s absolutely critical that we start having a public discussion,” said Barbara Brenner, executive director of Breast Cancer Action, an advocacy group. “I think of Avastin as a model that is showing us where the problem is.”
July 28, 2008
The Price of Beauty
As Doctors Cater to Looks, Skin Patients Wait
By NATASHA SINGER
Dr. Donald Richey, a dermatologist in Chico, Calif., has two office telephone numbers: calls to the number for patients seeking an appointment for skin conditions like acne and psoriasis often go straight to voice mail, but a full-time staff member fields calls on the dedicated line for cosmetic patients seeking beauty treatments like Botox.
Dr. Richey has two waiting rooms. The medical patients’ waiting room is comfortable, but the lounge for cosmetic clients is luxurious, with soft music and flowers.
And he has two kinds of treatment rooms: clinical-looking for skin disease patients, soothing for cosmetic laser patients.
“Cosmetic patients have a much more private environment than general medical patients because they expect that,” said Dr. Richey, who estimated that he spent about 40 percent of his time treating cosmetic patients. “We are a little bit more sensitive to their needs.”
Like airlines that offer first-class and coach sections, dermatology is fast becoming a two-tier business in which higher-paying customers often receive greater pampering. In some dermatologists’ offices, freer-spending cosmetic patients are given appointments more quickly than medical patients for whom health insurance pays fixed reimbursement fees.
In other offices, cosmetic patients spend more time with a doctor. And in still others, doctors employ a special receptionist, called a cosmetic concierge, for their beauty patients.
Dr. David M. Pariser, a dermatologist in Norfolk, Va., and the president-elect of the American Academy of Dermatology, said some practices did maintain preferential policies for cosmetic patients.
“The message is that the cosmetic patient is more important than the medical patient, and that’s not a good message,” Dr. Pariser said.
At a time when dermatologists are trying to advance the idea of a national skin cancer epidemic, such a two-tier system is raising concerns that the coddling of beauty patients may divert attention from skin diseases.
A study published last year in The Journal of the American Academy of Dermatology found that dermatologists in 11 American cities and one county offered faster appointments to a person calling about Botox than for someone calling about a changing mole, a possible sign of skin cancer.
And dermatologists nationwide are increasingly hiring nurse practitioners and physicians’ assistants, called physician extenders, who primarily see medical patients, according to a study published earlier this year in the same journal.
“What are the physician extenders doing? Medical dermatology,” Dr. Allan C. Halpern, chief of dermatology at Memorial Sloan-Kettering Cancer Center in Manhattan, said in a melanoma lecture at a dermatology conference this year. “What are the dermatologists doing? Cosmetic dermatology.”
There are no published studies showing that the rise of beauty procedures has caused harm to medical dermatology patients. If patients with skin problems have difficulty getting appointments, it is because over the last 30 years the demand to see skin doctors has far outstripped the number of physicians trained in the specialty, said Dr. Jack S. Resneck Jr., an assistant professor of dermatology at the medical school of the University of California, San Francisco.
Dr. Resneck, who researches professional issues in dermatology, said about 10,500 dermatologists now practiced in the United States, the majority devoting little time to vanity medicine.
Even so, dermatologists perform several million beauty treatments annually, according to estimates by the American Society for Dermatologic Surgery, including more than two million anti-wrinkle injection treatments last year — an increase of 130 percent over 2005.
Several patients interviewed for this article said that they believed the dermatologists they visited for medical care treated them as potential cosmetic consumers. Dianne Ryan, who works for an airline in Dallas, went to a dermatologist in her insurance network three years ago after her husband pointed out a mole growing on the side of her foot, she said. The doctor dismissed the mole as benign, she said, but recommended she buy his brand of bleaching cream for pigmentation on her face.
A few months later, Ms. Ryan said, she sought a second opinion from another dermatologist, whose diagnosis was melanoma.
“I don’t know if dermatology, with all the new technology, is turning away from melanoma or whether it is the glamour and excitement,” said Ms. Ryan, who was called by this reporter after an exchange in a chat room of the Melanoma Research Foundation. “If you do an extreme makeover on someone, you are a hero.”
Dermatology is one of the fields — along with plastic surgery and behavioral sleep medicine — in which patients are not only willing to pay for quality-of-life treatments that may not be covered by insurance, but also willing to pay much more for such treatments than insurers would pay for a medical procedure that takes a similar amount of time.
Some health insurers reimburse a doctor $60 to $90 for a visit including a full-body skin cancer check that might take 10 minutes; for Botox injections to the forehead, a doctor might receive $500 for 10 minutes, paid on the day of treatment.
According to a presentation for doctors from Allergan, the makers of Botox, a medical dermatology practice might have a net income of $387,198 annually, but a dermatologist who decreased focus on skin diseases while adding cosmetic medical procedures to a practice could net $695,850 annually. The same material advises doctors to “identify and segment high priority customers.”
People who wish to avoid a cosmetic-driven practice should simply seek appointments with medical dermatologists who focus on skin diseases, said Dr. Alexa B. Kimball, the vice chairwoman of dermatology at Massachusetts General Hospital in Boston.
But many dermatologists now offer both medical treatment and beauty procedures, which can confuse patients. And some doctors differentiate between patients — either within their own practices or by treating cosmetic patients in stand-alone facilities called medical spas.
Lecturers at the annual meeting of the American Academy of Dermatology, held in San Antonio in February, encouraged such segregation.
For example, Dr. Jason R. Lupton, a dermatologist in Del Mar, Calif., advised young physicians to oblige cosmetic patients by giving them appointments within seven days; empty appointment slots could later be filled with general dermatology patients, he said.
In a follow-up telephone interview, Dr. Lupton said that, in his own practice, he accommodated medical and cosmetic patients equally.
In an interview, Dr. Susan H. Weinkle, a dermatologist in Bradenton, Fla., said that she typically spends more time with cosmetic patients because they come in wanting to look better, the kind of amorphous desire that takes longer to satisfy than defined medical problems. One of her staff members always calls a beauty client to follow up, she said.
“It is very rare that you would call an acne patient and say, ‘How are you doing with that new prescription?’ ” Dr. Weinkle said. “But with a cosmetic patient, the consultant calls them the next day.”
This dual-class treatment system is not limited to the fanciest of private practices. Even academic institutions like the University of Michigan Health System in Ann Arbor are openly catering to beauty consumers. The Web site of the dermatology department warns a medical patient seeking an appointment to obtain a referral from a primary care physician “regardless of your type of insurance.”
A new profession — called aesthetic practice consultant — has emerged to advise doctors in the care of cosmetic patients.
“Instead of laying on an exam table with a paper liner, you have them lay on a sheet,” said Deborah Bish, a former nurse who works as a practice consultant in Yardley, Pa. “You have to class it up for these patients.”
It makes economic sense that dermatologists competing for Botox dollars want to create enticing environments, said Julie Cantor, a lawyer and medical school graduate who teaches a course in medical ethics at the law school of the University of California, Los Angeles. But Ms. Cantor said research was needed to determine whether such environmental changes alter a doctor’s behavior with medical patients.
“If you really started treating patients differently based on their ability to pay out of pocket, that’s a real problem,” Ms. Cantor said. “People who want their wrinkles fixed to go to a wedding should not be treated better than those who have psoriasis.”
Dr. Richey, the Chico, Calif., dermatologist, said that in his practice, the attention to cosmetic patients had no bearing on the treatment of medical patients; he maintains daily walk-in slots for medical patients with urgent skin problems, and many of his patients visit both sides of his practice.
“I don’t believe in differentiating,” Dr. Richey said.
Nonetheless, some medical patients said that they believed other dermatologists brushed off their medical concerns in favor of marketing cosmetic procedures. Melissa Bundy, a health communications manager in Atlanta, said that several years ago she went to a dermatologist who seemed more interested in selling face treatments than in conducting a thorough skin cancer examination. She has since switched doctors.
“Cosmetic things, it’s a really great business,” Ms. Bundy said. “But it really does seem to be at the expense of people like me getting the medical services that we are looking for.”
July 28, 2008, 10:20 pm
Readers’ Questions: Options for Brain Cancer
By Derek Raghavan, M.D., Ph.D
Brain tumors, often in the news, raise a frightening specter for the public. Recent reports that Senator Edward M. Kennedy of Massachusetts is suffering from a brain tumor has raised the level of angst. To add to the anxiety, we are now being told that cellphones might be responsible for the increase in this type of cancer.
In Tuesday’s paper, The New York Times reports on the behind-the-scenes debate surrounding surgery for Senator Kennedy’s brain tumor. How can top specialists come up with so many apparently differing opinions about treatment? Well, in many areas of medicine, there often is more than just one way to achieve the best outcome, and different specialists will sometimes see things different ways.
To help put this news in perspective, let’s look at some of the facts. And to start, it’s useful to distinguish between the two major groups of brain tumors: primary and secondary.
Primary brain tumors arise from the brain tissue itself and include a spectrum of disorders of varying severity. At one end are relatively benign growths like meningiomas, which arise from the tissues lining the brain and are often associated with a long life expectancy. At the other extreme are very aggressive and scary malignancies arising directly from brain tissue. An example of this type of primary brain tumor is glioblastoma, an aggressive, often fast-growing tumor that is often, though not always, associated with a poor prognosis.
Secondary brain tumors arise outside of the brain. Cancer cells then seed the brain, often carried there by the bloodstream. Common cancers that lead to secondary, or metastatic, brain tumors include those arising in the lung, breast or kidney. Malignant melanoma, the most deadly form of skin cancer, also often spreads to the brain.
With brain tumors, the key issue is to define the type of tumor being treated. The prognosis is strongly influenced by the cancer’s origin: whether it is a primary tumor that originates from within the brain, or a secondary cancer that has metastasized from elsewhere. Other important factors include the location and size of the tumor within the brain, which helps determine whether the tumor can be fully removed.
In Senator Kennedy’s case, it is difficult to guess at his prognosis, since the precise type of tumor has not been publicly disclosed. Although it has been reported he has a glioma, there are many types of gliomas, each with very different likely outcomes and different required treatments. Knowing the precise type of cancer he has is very important, especially these days when we can look at the genes expressed within brain tumors and sometimes learn important information about the likely prognosis or response to treatment.
In the case of a primary brain tumor like a glioblastoma, a type of glioma, a key decision is whether curative surgery is technically possible. Not all parts of the brain can be removed surgically without killing the patient. In addition, surgery is sometimes done not to treat the disease but to achieve a diagnosis: to remove some tissue and identify the type of tumor under the microscope. For other types of brain tumors that are less aggressive, such as meningiomas, surgery is usually the treatment of choice.
A big piece of the decision regarding surgery for brain cancer is the physical cost to the patient, including any loss of physical and thought function that might ensue from surgery. Depending on the site of the tumor, there may be a risk of losing speech or some movement. Different surgeons and different patients will be prepared to take different levels of risk. Fortunately, surgery is not the only option, and for some types of tumors, chemotherapy plus radiotherapy give results similar to those for surgery.
Regardless of the treatment options, better outcomes for brain tumors are needed, and vigorous research is currently in progress. On the basis of public information, it is too early to make any specific comment on Senator Kennedy’s situation, other than to note that he is entitled, like everyone else, to his privacy while being treated.
This week, I’ll be answering some of your questions about brain tumors and cancer. Although I cannot give specific medical advice regarding individual cases, I will be available to discuss such issues as metastatic cancer, the impact of cellphones and what’s new in the molecular biology of brain tumors. Please post your questions in the comment box below.
Dr. Derek Raghavan, a medical oncologist, is chair and director of the Cleveland Clinic Taussig Cancer Center.
August 12, 2008
Early Test for Cancer Isn’t Always Best Course
By TARA PARKER-POPE
Sometimes what you don’t know might end up being better for you.
For years patients have been told that early cancer detection saves lives. Find the cancer before the symptoms appear, the thinking goes, and you’ve got a better chance of beating the disease.
So it might have seemed surprising last week when a panel of leading medical experts offered exactly the opposite advice. They urged doctors to stop screening older men for prostate cancer, which will kill an estimated 28,600 men in the United States this year.
Their advice offered a look at the potential downside of cancer screening and our seemingly endless quest to detect cancer early in otherwise healthy people. In this case, for men 75 and older, the United States Preventive Services Task Force concluded that screening for prostate cancer does more harm than good.
“We’ve done a great job in public health convincing people that cancer screening tests work,” said Peter B. Bach, a pulmonologist and epidemiologist at Memorial Sloan-Kettering Cancer Center in New York City. “We’re uncomfortable with the notion that some screening tests work and others don’t. That seems mystifying to people.”
But the reality is that while some cancer screening tests — like the Pap smear for cervical cancer or mammography for breast cancer — clearly save lives, the benefits of other screening tests are less clear.
Studies of lung cancer screening, for instance, have failed to prove that it prolongs life. A mass screening for neuroblastoma in Japanese infants was halted after it became clear that the effort wasn’t saving children and worse, led to risky treatments of tumors that weren’t life threatening.
The case seemed stronger for screening for prostate cancer. By some measures, death rates from the disease in the United States have plummeted since the introduction of the screening test for prostate specific antigen, which detects levels of a protein that can signal prostate cancer.
The data, in fact, are highly misleading. The introduction of screening can trigger big statistical fluctuations that can be difficult to interpret. But if you look at prostate cancer statistics in the 1970s, long before screening was introduced, death rates have dropped only slightly since then. The small decline seems largely because of improvements in treatment, many experts say, though others point to early detection as the reason.
Whether there really is a measurable benefit from PSA screening for younger men won’t be known for a few more years, after data from two major clinical trials studying the test are reported.
How can it be that finding prostate cancer early doesn’t help save lives? For starters, a large percentage of prostate cancers aren’t deadly. They are slow growing and unlikely to result in any symptoms before the end of a man’s natural life expectancy. By some estimates, as many as 44 percent of the men who are treated for prostate cancer as a result of PSA testing didn’t need to be. Had they been left alone, they would have died of something else and never known they had cancer.
“Screening tests don’t only pick up life-threatening cancers, they pick up tumors that look identical to traditional tumors, but they don’t have the same biologic behavior,” said Dr. Barry Kramer, associate director for disease prevention at the National Institutes of Health. “Some are so slow growing they never would have caused medical problems in the person’s natural life span.”
In the case of PSA testing, the Preventive Services Task Force, an expert panel that makes recommendations about preventive care for healthy people, said there was not enough evidence to recommend for or against screening of younger men, although they urged doctors to advise men of all the risks and benefits of screening. But they did conclude that 75 is the age at which the risks clearly begin to outweigh the benefits, and the disease, if detected, would most likely not have a meaningful effect on life expectancy.
Another problem with determining the value of screening is that it results in “lead time bias.” For instance, someone diagnosed with lung cancer at the age of 65 may die at 67 and be remembered as a two-year survivor. If the same man had been diagnosed at 57 through screening and died at the age of 67, he would be known as a 10-year survivor. That sounds a lot better, but the reality is that diagnosis and treatment didn’t prolong his life. He died at 67 either way.
“Even a harmful screening test could appear on the surface as a helpful test,” Dr. Kramer said. “Because you measure survival from the date of diagnosis, even if the person dies of the same cause on the same day they would have without screening, it looks like survival was longer.”
Any screening test can lead to false positives, followed by invasive and risky tests. Large numbers of people often end up being poked, prodded and tested only to discover they’re fine.
Biopsies to detect prostate cancer get mixed reviews. Some men find them to be a minor discomfort; others say they were left in debilitating pain. Once cancer is found, surgery, radiation or hormone therapy, or “watchful waiting,” may be advised.
Treatments for prostate cancer can cause significant harm, rendering men incontinent or impotent, or with other urethral, bowel or bladder problems. Hormone treatments can cause weight gain, hot flashes, loss of muscle tone and osteoporosis.
“It’s just a needle stick, but the cascade of events that follows are fairly serious,” Dr. Bach said. “I think the burden is on medicine to try and generate some evidence that the net benefits are there before drawing that tube of blood.”
The problem with prostate screening is that some men are very likely to have been saved by early detection. But how many have been hurt?
“I’m a little worried we may look back on the prostate cancer screening era, after we learn results of clinical trials, and see that we’ve harmed a lot of people without doing them good,” said Dr. David Ransohoff, a professor of medicine and cancer screening researcher at the University of North Carolina at Chapel Hill. “By being so aggressive with so many people, did we do the right thing? I don’t know that it’s going to turn out that way.”
August 19, 2008
The Doctor’s World
At Meeting on AIDS, Focus Shifts to Long Haul
By LAWRENCE K. ALTMAN, M.D
MEXICO CITY — Two years have passed since the 16th International AIDS Conference in Toronto, and the contrast between that meeting and the 17th, which ended here this month, was humbling.
In Toronto, the mood was almost giddy, with celebrities like Bill Gates and Bill Clinton drawing huge crowds as they championed the development of H.I.V. vaccines and microbicides.
Though the meeting this month had its circuslike elements, the mood was much more sober. No major breakthroughs were announced, and cutting-edge research findings were rare. The great strides that many researchers thought they were on the verge of making in 2006 — in vaccines, microbicides and herpes-suppressive drugs to reduce H.I.V. transmission — have failed to materialize.
The focus here was on the longer haul. There were renewed calls for strong advocacy and financing to sustain gains already made, like promoting more antiretroviral therapy in poorer countries, along with male circumcision and behavior modification.
While Mr. Gates did not attend, Mr. Clinton did. He called the conferences important in part “because they enable us to measure our progress since the last meeting, to openly acknowledge continuing problems, to evaluate the positive and negative new developments.”
With no magic bullet in sight, he said, the need now is to combine efforts to advance prevention and treatment.
The recent setbacks led many AIDS scientists to reflect on the frustrating, complicated courses of their endeavors. Still, a certain smugness could be detected among some researchers, who still expect their trials to produce favorable findings, even though such success is far from guaranteed. Initial results from trials of a daily pill that would prevent H.I.V. may be ready next year.
In explaining the recent failures of vaccine and other trials, many scientists blamed public naïveté, saying laypeople do not understand that research gains usually come in increments and that progress often follows a zigzag course.
But that view overlooks the flaws in the process itself. Many researchers write papers as if they knew what they were doing from the outset, when, in fact, serendipity plays an important role.
Failure can have different meanings for scientists and the public.
Some scientists view failure as a momentary setback on the road to success. But that can be determined only in retrospect, and only if success is achieved. The public may see failure as bad science. Not necessarily so: scientists can learn from any trial if it is well designed and well executed. But how much the recent failures can contribute to future trials is uncertain.
There were calls for innovation and recruiting more young investigators to the AIDS field. As Alan Bernstein, executive director of the Global H.I.V. Vaccine Enterprise in Manhattan, put it, “The engines of discovery are new people.”
Dr. Bernstein noted that recruiting new workers should be less of a problem than in the past because of an explosion of interest on university campuses about global health.
Since its discovery in 1981, AIDS has rivaled the worst epidemics in history. An estimated 25 million people have died, and 33 million are living with H.I.V.
An important handicap in tracking and controlling the epidemic has been an inability to get timely and accurate data about current transmission of the virus. Rough estimates have come from calculating backward, from when AIDS was diagnosed to when the virus first entered the body. That interval can vary but usually is about 8 to 10 years.
Dr. Jorge Saavedra, director of the Mexican national AIDS program, underscored the imperative for such information by saying that “if you do not follow the epidemiology of H.I.V.” and the scientific evidence, “then we will lose the fight against H.I.V.”
Now, a new test developed by the Centers for Disease Control and Prevention promises a greater ability to pinpoint hot spots of new infections and to control them more quickly, at least in developed countries. The test needs to be refined for use in poor countries, the disease centers said.
While many participants applauded development of the test, they also criticized the federal agency for an eight-month delay in reporting its success.
The best weapon against H.I.V. would be a vaccine. But despite the hubris of leading scientists who predicted quick marketing of a vaccine after the virus was discovered in the mid-1980s, none is on the horizon.
Last year, the most promising vaccine candidate failed in trials.
“Development of a vaccine is still more of an art than a science,” said Dr. Tadataka Yamada, an official of the Bill and Melinda Gates Foundation in Seattle. He added, “No one country, any one scientist, any one team of scientists will develop the vaccine.”
A major obstacle is the inability to identify precisely what components of the immune system are responsible for combating H.I.V. For other vaccines, scientists look to the so-called correlates of immunity, which include antibodies that neutralize the virus and other substances that protect against it.
Since the Toronto conference in 2006, about two million people, mostly in poor countries, have started receiving antiretroviral drugs. But the need is far greater: in the same period, five million people became infected.
“The lack of secure and reliable drug supplies is the Achilles’ heel of antiretroviral programs,” said Gregg Gonsalves of the AIDS and Rights Alliance for Southern Africa. “Central medical stores in many countries often cannot handle this task.”
Reports of the number of people being treated in poor countries are now based on estimates. Mr. Gonsalves urged regular reporting of reliable national data to the World Health Organization.
A major concern is that H.I.V. will become resistant to the existing drugs, necessitating different, costlier second-line drugs. Who will pay for these drugs?
Although the United States has licensed 25 drugs in seven classes for H.I.V., doctors do not know what combination is the best for initial treatment and when to start them.
A panel of the International AIDS Society, which runs the meetings, issued new guidelines urging earlier treatment of H.I.V. in the developed world. Because the recommendations are based on expert opinion, many called for trials to provide them with a more scientific underpinning.
The combinations of antiretroviral drugs introduced in the late 1990s have turned AIDS from a usually fatal disease into one that can be managed as a chronic disease. But a cure is elusive.
Most participants urged further efforts to develop a cure and vaccine; unless researchers make the effort no one will ever know if they can be achieved.
Ten trials of microbicides — chemicals that are inserted into the vagina or rectum to prevent H.I.V. infection — have failed.
But researchers expressed renewed optimism that new trials will show the effectiveness of a second generation that incorporates antiretroviral drugs into a gel or a vaginal ring.
Whatever means are found to improve prevention of H.I.V., health workers should pay more attention to marketing and business methods, said Dr. Peter Piot, the outgoing director of the United Nations AIDS program. Calling current public health approaches to H.I.V. prevention “amateurish,” he said public health must be marketed as effectively as commercial products.
An underlying concern among participants was the potential for a strong reaction by critics who say that AIDS consumes too great a share of the resources available for all ailments and that efforts focused on only one disease are destroying primary health systems in poor countries.
There was enthusiastic support for the legislation passed last month allowing the United States to spend $48 billion over the next five years to expand President Bush’s program to prevent and treat AIDS in a number of foreign countries. It is believed to be the United States’ most ambitious foreign public-health program. But some critics have raised questions about whether the United States is promising lifetime therapy for recipients, in effect engaging in a foreign aid entitlement program.
To this reporter, who has covered International AIDS Conferences since they began, the shift is unmistakable — from a stronger emphasis on science to more of a convention atmosphere. The change is due partly to the restricted number of scientists that the United States government sends to the meetings and to many scientists’ preference for smaller, quieter meetings that are not interrupted by protesters.
No conference has been held in the United States since 1990 — as a protest against the government’s policy to refuse visas to people with H.I.V. But the recent financing legislation removes that ban, possibly returning the conference to the United States in a few years.
Meanwhile, the next conference will take place in Vienna in 2010. And unexpected developments, good or bad, could well arise. As Dr. Piot said, the AIDS epidemic “has always come up with new surprises.”
Q: What do you think of the study showing that eating tomatoes offers no protection against prostate cancer and that, in fact, consumption of large amounts of beta carotene may increase the incidence of aggressive prostate cancer?
A: The study you're talking about got a lot of publicity, but I wouldn't rush to dismiss the cancer-protective effect of lycopene found in tomatoes on the basis of these findings.
Here's what happened: Researchers from the Fred Hutchinson Cancer Research Center in Seattle selected men already enrolled in the Prostate, Lung, Colorectal and Ovarian Screening Trial sponsored by the National Cancer Institute. A total of 28,243 people between the ages of 55 and 74 participated in the study. None of the male participants had a history of prostate cancer when they signed up.
Over eight years, 692 of the men developed prostate cancer and were matched to 844 men in the study who did not. The investigators found no significant difference in blood levels of lycopene between the men who developed cancer and those who didn't. Lycopene is the red carotenoid pigment in tomatoes believed to account for lower prostate cancer risk in men who eat more tomato products.
The investigators also saw an increased risk of aggressive prostate cancer (disease that has spread beyond the gland) among men whose blood levels of beta carotene was higher than it was among other men in the study. (Beta-carotene is a related pigment in the carotenoid family, found in many brightly coloured fruits and vegetables, including tomatoes.)
While this study was widely touted as including more than 28,000 men, the conclusion was based on data from just over 1,500. Instead of carefully following diets for eight years and then comparing consumption of lycopene-rich food to the development of prostate cancer, they selected those who had already developed prostate cancer and tried to make assumptions from blood levels of carotenoids.
And while these investigators concluded that on the basis of their retrospective analytical methods that lycopene and other carotenoids had no effect on prostate cancer, we have very good evidence from other studies that lycopene does in fact lower the risk.
The U.S. Food and Drug Administration scrutinized this evidence very carefully before deciding in 2005 that tomato-based products could carry the claim that they may reduce the risks of prostate, gastric, ovarian and pancreatic cancers. I don't think this latest study makes a compelling case against the findings of earlier trials, many of which were actually designed to look at the lycopene/cancer-risk connection, rather than draw conclusions after cancer developed.
In other prostate cancer news, a study published in the May 16, 2007 issue of the Journal of the National Cancer Institute reported that men who take excessive amounts of multivitamins had a higher risk of aggressive prostate cancer and twice the risk of fatal prostate cancer as men who took no multivitamins.
Interestingly, while scientists actually found no link between supplement use and the development of early or localized prostate cancer, they did suggest that those who consumed more than seven multivitamins a week appeared to increase their risk of developing advanced and fatal prostate cancer.
Overall, the data failed to show a relationship between using supplements and risks of actually developing prostate cancer, and the data from the high-supplement-use group is confounded by strong family histories of the disease in these men, suggesting that multivitamin use may not actually have any bearing.
Q: What's the story with using shark cartilage for cancer treatment?
A: The notion that shark cartilage might be a useful cancer treatment springs from the mistaken idea that sharks don't get cancer. They do. However, laboratory studies have suggested that substances in shark cartilage may inhibit angiogenesis, the formation of new blood vessels that tumors need to grow.
The good news ends there. Clinical trials over the past two decades have failed to show that shark-cartilage products benefit patients. The latest study, from M.D. Anderson Cancer Center in Texas, found that shark cartilage failed to improve survival of patients with stage-3, non-small-cell lung cancer. (They were also being treated with chemotherapy and radiation.) Researchers randomly assigned 384 patients at 53 sites in the United States and in Canada to take four ounces of shark cartilage extract or a placebo twice daily.
Those on the shark cartilage survived about 14.4 months, compared to 15.6 months for those on placebo, a difference that wasn't statistically significant. In this study, the shark cartilage used was Neovastat, a product developed as a prescription pharmaceutical and never sold over-the-counter, unlike other forms of shark cartilage previously studied.
Findings from a study published in the July 1, 2005, issue of the journal Cancer showed that adding powdered shark cartilage to standard cancer therapy didn't help patients with advanced breast or colorectal cancer.
Half of the 88 participants mixed shark cartilage powder with juice or water, while the other half used a placebo that looked and smelled like shark cartilage powder. But the patients couldn't tolerate either preparation: After a month, half the patients in both groups had given up the drinks.
Other studies have reported side effects such as nausea, vomiting, abdominal cramps, bloating, constipation, abnormally low blood pressure, general weakness and abnormally high levels of calcium in the blood (possibly due to the high level of calcium in shark cartilage).
Overall, there's no compelling proof that shark cartilage products do cancer patients any good. What's more, these preparations are detrimental to the environment because demand for their cartilage contributes to the over-fishing of sharks in the wild, endangering the survival of some species. Don't waste your time or money on this stuff.
Dr. Andrew Weil is director of the program of Integrative Medicine of the College of Medicine, University of Arizona. He is an internationally recognized expert on medicinal plants, alternative medicine and the reform of medical education.
This is a story about M.R.I.’s, those amazing scans that can show tissue injury and bone damage, inflammation and fluid accumulation. Except when they can’t and you think they can.
I found out about magnetic resonance imaging tests when I injured my forefoot running. All of a sudden, halfway through a run, my foot hurt so much that I had to stop.
But an M.R.I. at a local radiology center found nothing wrong.
That, of course, was what I wanted to hear. So I spent five days waiting for it to feel better, taking the anti-inflammatory drugs ibuprofen and naproxen, using an elliptical cross-trainer, and riding my road bike with its clipless pedals that attach themselves to my bicycling shoes. By then, my foot hurt so much I had to walk on my heel. I was beginning to doubt that scan: it was hard to believe nothing was wrong. So I went to the Hospital for Special Surgery in New York for a second opinion from Dr. John G. Kennedy, an orthopedist who specializes in sports-related lower-limb injuries. And there I had another M.R.I.
It showed a serious stress fracture, a hairline crack in a metatarsal bone in my forefoot. It was so serious, in fact, that Dr. Kennedy warned that I risked surgery if I continued activities like cycling and the elliptical cross-trainer, which make such injuries worse. And I had to stop taking anti-inflammatory drugs, since they impede bone healing.
As I hobbled around the office on crutches, one of my colleagues, James Glanz, asked what had happened. As we chatted, it turned out that he had had a much more sobering experience than mine.
Jim, the Baghdad bureau chief for The New York Times, was playing touch football in New York in late 2005 when he landed hard while diving to make a catch, both elbows hitting the ground at once. The next day, his fingers and hands hurt so much he couldn’t type.
But an M.R.I. showed nothing except some bulging disks in his neck that, he was told, were common in people his age, 50. He was advised to do neck exercises, and eventually he felt better.
About a year later, he fell again while playing football. His symptoms came roaring back.
The worst was when he woke up in the morning, Jim said. The two middle fingers on each hand were so stiff they would not even bend. He would massage his fingers and loosen them, but his hands and knuckles ached all day. He tried ibuprofen, to little avail.
Finally, last spring, he sought help at New York University, where he had another M.R.I. It turned out he had a nerve impingement so serious that he was warned that he risked permanent paralysis if he did not have surgery. So this summer, he had a major operation called a French-door laminoplasty, in which his surgeon, Dr. Ronald Moskovich at the N.Y.U. Hospital for Joint Diseases, opened and widened four or five vertebrae to free the trapped nerves.
How could M.R.I.’s have come to such different conclusions for both Jim and me?
Jim asked his doctors whether he could have really had nothing wrong at the time of his first scan. Unlikely, they replied, although they cautioned that no one had directly compared the two scans.
I asked Dr. Kennedy the same question and received the same answer. He explained that in my case the quality of the two images was vastly different. “It’s like the difference between a black-and-white TV and HDTV,” he said.
All well and good, but how was I supposed to know? The radiology center I first went to is accredited by the American College of Radiology, and there is no way I can tell a good M.R.I. image from a bad one. In fact, I never even saw the images. All I saw were the radiologists’ reports.
Academic radiologists say that, unfortunately, they see patients like Jim and me all the time.
“That’s the bane of our existence in an academic medical center,” said Dr. Howard P. Forman, a professor of diagnostic radiology at Yale University School of Medicine.
And it’s not just patients who have to deal with the problem, said Dr. William C. Black, a professor of radiology and community and family medicine at Dartmouth Medical School. Doctors do, too. Radiology centers send written reports to doctors, but the doctors may have no idea whether the M.R.I. was done well and interpreted well. “It’s a huge problem,” Dr. Black said.
Unlike C.T. scans or X-rays, which transmit radiation through the body to produce images, M.R.I.’s use powerful magnets and radio waves to manipulate protons in the body’s hydrogen atoms. The idea, said Dr. Andrew H. Haims, a diagnostic radiologist at Yale, is that protons in different types of tissue respond in distinctive ways to this pushing and prodding. The differing responses reveal the characteristics of the tissue.
Magnetic resonance machines, though, vary enormously, and not just in the strength of their magnets. Even more important, radiologists say, is the quality of the imaging coils they put around the body part being scanned and the computer programs they use to control the imaging and to analyze the images. And there is a huge variability in skill among the technicians doing the scans.
Dr. Forman said that at the very least, patients should go to radiology centers accredited by the American College of Radiology. But he added that accreditation does not tell you whether your scan will be done with a machine that is several generations removed from the best available today; whether the scanning is programmed to pick up your particular problem; or whether the receiving coil that picks up signals from the magnet is sufficiently sensitive.
G. Scott Gazelle, a professor of radiology at Harvard Medical School, shared Dr. Forman’s opinions.
“People don’t understand that there are these differences,” he said, adding that radiology centers that do not keep up will be doing a less than ideal job. “The pace of technology development is staggering,” he said.
Then there is the question of how skilled is the radiologist who reads your scans.
At Massachusetts General Hospital, for example, Dr. Gazelle said, “musculoskeletal M.R.I.’s are read by someone who does musculoskeletal imaging every day” — and not “by someone who reads chest M.R.I.’s one day and musculoskeletal M.R.I.’s the next.”
Dr. Forman says it pays to check the credentials of a center’s radiologists.
“If you say, ‘Who will be reading my scan?’ and they say, ‘One of our radiologists,’ you don’t go to a place like that,” he said. (I checked the Web site of the first center I went to. The radiologist who read my scan was a generalist with no special training.)
Of course, it may not be feasible to go to an academic medical center where subspecialists will read your images. And even if you do, said Dr. James Thrall, chairman of the board of chancellors of the American College of Radiology, “scans, as good as they are, are not perfect.”
”I wouldn’t equate a negative scan as being an 100 percent indicator that nothing is wrong,” he added. So if you are told nothing is wrong because a scan was negative and you are having alarming symptoms, you may want to seek a second opinion.
And don’t forget, said Dr. Jeffrey Jarvik, a professor of radiology and neurological surgery at the University of Washington, the point of an M.R.I., or any imaging study, is to help make a diagnosis that will improve your health. Often imaging is unnecessary: a good exam will reveal what’s wrong, and the treatment will be the same with or without the scan.
Just as big a problem as the erratic quality of scans is the tendency of doctors and patients to rely on them too much.
“There’s been a shift in medicine toward relying on imaging instead of a history and examination,” Dr. Jarvik said.
And I suspect that that was one reason Jim and I were so misled.
“Pain is a way for Mother Nature to talk to us,” Dr. Thrall told me. “And when our invented process for understanding is at odds with what Mother Nature is telling us, we had better listen to Mother Nature.”
Doctors baffled by an unexplained rash on people's ears or cheeks should be on alert for a skin allergy caused by too much cellphone use, the British Association of Dermatologists said Thursday.
Citing published studies, the group said a red or itchy rash, known as "mobile phone dermatitis," affects people who develop an allergic reaction to the nickel surface on mobile phones after spending long periods of time on the devices.
"It is worth doctors bearing this condition in mind if they see a patient with a rash on the cheek or ear that cannot otherwise be explained," it said.
The British group said many doctors were unaware cellphones could cause the condition.
Safety concerns over cellphones has grown as more people rely on them for everyday communication, although the evidence to date has given the technology a clean bill of health when it comes to serious conditions like brain cancer.
"In mobile phone dermatitis, the rash would typically occur on the cheek or ear, depending on where the metal part of the phone comes into contact with the skin," the group said in a statement.
"In theory it could even occur on the fingers if you spend a lot of time texting on metal menu buttons."
Nickel is a metal found in products, ranging from mobile phones to jewelry to belt buckles and is one of the most common causes of allergic contact dermatitis, according to the Mayo Clinic in the United States.
Earlier this year, Lionel Bercovitch of Brown University in Rhode Island and colleagues tested 22 popular handsets from eight different manufacturers and found nickel in 10 of them.
You’re born with a little over a pint of it, by adulthood you’re up to four or five quarts, and if at any point you suddenly shed more than a third of your share, you must either get a transfusion or prepare to meet your mortician.
Human cultures have long recognized that blood is essential to life and have ascribed to it a vast array of magical powers and metaphorical subroutines. Blood poultices and blood beverages were said to cure blindness, headaches, gout, goiter, worms and gray hair. The Bible mentions blood more than 400 times, William Shakespeare close to 700. It’s “all in the blood,” your temperament, your fate. Are you a blue-blooded Mesopotamian princess or a red-blooded American male?
Yet to scientists who study blood, even the most extravagant blood lore pales in comparison to the biochemical, evolutionary and engineering marvels of the genuine article.
The fluid tissue we call blood not only feeds us and cleans us, delivering fresh oxygen and other nutrients to all 100 trillion cells of the body and flushing out carbon dioxide, ammonia and other metabolic trash. It not only houses the immune system that defends us against the world.
Our blood is the foundation of our very existence as multicellular animals, said Andrew Schafer, a professor at Weill Cornell Medical College and the outgoing president of the American Society of Hematology. Blood is the one tissue that comes into contact with every other tissue of the body, and it is through blood that our disparate parts communicate, through blood that our organs cooperate. Without a circulatory system, there would be no internal civilization, no means of ensuring orderly devotion to the common cause that is us.
“It’s an enormous communications network,” Dr. Schafer said — the original cellphone system, if you will, 100 trillion users strong.
Blood can also be thought of as a private ocean, a recapitulation of what life was like for all the years we spent drifting as microscopic, single-celled organisms, “taking up nutrients from sea water and then eliminating waste products back into sea water,” Dr. Schafer said. Not only is blood mostly water, but the watery portion of blood, the plasma, has a concentration of salt and other ions that is remarkably similar to sea water.
Of course, we can’t rely on wind and weather to keep our hidden seas salubriously churned and aerated, so we have evolved an active respirator and pumping mechanism, the lungs and heart. Our eight pints of blood circulate through the powerhouse duet maybe 60 times an hour, absorbing recently inhaled oxygen from the honeycombed fabric of the lungs and proceeding into the thickly muscled heart, which then shoots the enriched fluid outward.
Oxygen allocation is the task of the red blood cells, which hematology researchers refer to with a mix of affection and awe. “Red cells have enormous capabilities,” said Stanley Schrier of Stanford University’s School of Medicine. They give up so much to make room for their hemoglobin, the proteins that can latch onto oxygen and that give blood its brilliant grenadine sheen. Alone among body cells, red cells at maturity jettison their nucleus and DNA to accommodate their cargo.
And oh how roughly they are treated. A red cell at rest looks like a plump bialy and measures about 8 microns, or .0003 inches, across. Yet to reach every far-flung, oxygen-hungry customer, the cells must squeeze through capillaries less than half their width, which they accomplish by squashing down into threads that then crawl in single file along the capillary wall, pulling themselves forward, Dr. Schrier said, like tank treads gripping the road.
Blood is also a genius, able to sustain two contradictory states without going mad. To ceaselessly shuttle along the body’s 60,000 miles of arteries, veins and capillaries, blood must be fluid, our trusty souvenir sea.
Yet even though we constantly replace components of our blood, directing the aged and the battered to the spleen and liver — the “graveyards for blood cells,” Dr. Schafer said — and replenishing them with fresh blood cells forged in the bone marrow, the turnover cycle is gradual and we can’t afford to lose everything in one big gush wrought by a predator’s gash. Blood, then, departs from sea water, or, for that matter, from breast milk, another prized body fluid, in one outstanding way: it is always poised to clot, to relinquish liquidity and assume solidity.
In deciding whether to flow or clot, blood takes its cues from its surroundings. As blood glides through the bulk of its tubular circuitry, the comparatively heavy red cells are driven toward the center of the swirl, said James N. George, a hematologist at the University of Oklahoma Health Sciences Center, while two other, lighter characters are pushed out to the periphery: the white blood cells that operate as immune warriors, and the platelets, tiny cells that have been called the Band-Aids of the body. Their marginalization is no accident. “They’re surveillance cells,” Dr. George said. “It’s almost like they’re scouting for trouble.”
White blood cells look for signs of invasive microbes, while platelets scan for leaks. As long as the platelets detect the Teflon-like surface of unbroken endothelium, the tissue with which blood vessels are lined, they keep moving.
But even the tiniest cut or gap in the smooth vessel wall will expose some of the fibrous strands beneath, and the platelets are primed to instantly detect the imperfection. A passing platelet will stick to the raggedy strand and change shape, from round to octopoid, which in turn attracts other platelets, forming a little clump. “If the cut is small, that’s all you need,” Dr. George said. If not, the next phase of flood control begins. Signals from the platelets arouse the blood’s clotting factors, free-floating proteins that can cross-link together into bigger, better Band-Aids.
“Platelets and clotting factors,” Dr. Schrier said. “It’s a marriage made in heaven.”
Up to a point. Just as our immune cells can go awry and begin attacking our own body tissue, so an overzealous clot response can have dire consequences. Should a clot happen to cut off blood flow to a vital organ like the heart or brain, the only one playing the harp will be you.
October 24, 2008
Half of Doctors Routinely Prescribe Placebos
By GARDINER HARRIS
Half of all American doctors responding to a nationwide survey say they regularly prescribe placebos to patients. The results trouble medical ethicists, who say more research is needed to determine whether doctors must deceive patients in order for placebos to work.
The study involved 679 internists and rheumatologists chosen randomly from a national list of such doctors. In response to three questions included as part of the larger survey, about half reported recommending placebos regularly. Surveys in Denmark, Israel, Britain, Sweden and New Zealand have found similar results.
The most common placebos the American doctors reported using were headache pills and vitamins, but a significant number also reported prescribing antibiotics and sedatives. Although these drugs, contrary to the usual definition of placebos, are not inert, doctors reported using them for their effect on patients’ psyches, not their bodies.
In most cases, doctors who recommended placebos described them to patients as “a medicine not typically used for your condition but might benefit you,” the survey found. Only 5 percent described the treatment to patients as “a placebo.”
The study is being published in BMJ, formerly The British Medical Journal. One of the authors, Franklin G. Miller, was among the medical ethicists who said they were troubled by the results.
“This is the doctor-patient relationship, and our expectations about being truthful about what’s going on and about getting informed consent should give us pause about deception,” said Dr. Miller, director of the research ethics program in the department of bioethics at the National Institutes of Health.
Dr. William Schreiber, an internist in Louisville, Ky., at first said in an interview that he did not believe the survey’s results, because, he said, few doctors he knows routinely prescribe placebos.
But when asked how he treated fibromyalgia or other conditions that many doctors suspect are largely psychosomatic, Dr. Schreiber changed his mind. “The problem is that most of those people are very difficult patients, and it’s a whole lot easier to give them something like a big dose of Aleve,” he said. “Is that a placebo treatment? Depending on how you define it, I guess it is.”
But antibiotics and sedatives are not placebos, he said.
The American Medical Association discourages the use of placebos by doctors when represented as helpful.
“In the clinical setting, the use of a placebo without the patient’s knowledge may undermine trust, compromise the patient-physician relationship and result in medical harm to the patient,” the group’s policy states.
Controlled clinical trials have hinted that placebos may have powerful effects. Some 30 percent to 40 percent of depressed patients who are given placebos get better, a treatment effect that antidepressants barely top. Placebos have also proved effective against hypertension and pain.
But despite much attention given to the power of placebos, basic questions about them remain unanswered: Are they any better than no treatment at all? Must people be deceived into believing that a treatment is active for a placebo to work?
Some studies have hinted at answers, but experts say far more work is needed.
Dr. Howard Brody, director of the Institute for the Medical Humanities at the University of Texas Medical Branch, in Galveston, said the popularity of alternative medical treatments had led many doctors to embrace placebos as a potentially useful tool. But, Dr. Brody said, doctors should resist using placebos, because they reinforce the deleterious notion that “when something is the matter with you, you will not get better unless you swallow pills.”
Earlier this year, a Maryland mother announced that she would start selling dextrose tablets as a children’s placebo called Obecalp, for “placebo” spelled backward.
Dr. Ezekiel J. Emanuel, one of the study’s authors, said doctors should not prescribe antibiotics or sedatives as placebos, given those drugs’ risks. Use of less active placebos is understandable, he said, since risks are low.
“Everyone comes out happy: the doctor is happy, the patient is happy,” said Dr. Emanuel, chairman of the bioethics department at the health institutes. “But ethical challenges remain.”
CHICAGO - Rheumatoid arthritis nearly doubles the risk of having a heart attack within the first 10 years of diagnosis, Swedish researchers said Saturday.
The research, to be presented this week at the American College of Rheumatology's annual meeting in San Francisco, confirms rheumatoid arthritis raises the risk of heart attacks and suggests this risk begins early on in the disease.
About 20 million people worldwide have rheumatoid arthritis, an autoimmune disease caused when the body confuses healthy tissues for foreign substances and attacks itself.
The disease causes pain, stiffness and swelling in multiple joints, and inflammation can develop in other organs as well.
Other studies have suggested rheumatoid arthritis raises heart risks.
But the study by Marie Gunnarsson, a graduate student at the Karolinska Institutet in Stockholm, wanted to take the research a step further by seeing how quickly these risks can rise.
She used data on 7,954 patients in Sweden who were newly diagnosed and matched them with 38,913 people in the general population. The two groups were followed for more than 10 years.
They found that after their diagnosis, the heart risks for people rose steadily.
Obese kids' arteries age faster: study
Generation of children at risk of premature disease
Canwest News Service
Wednesday, November 12, 2008
The arteries of obese children may be aging 30 years faster than normal, new research suggests.
A study of 70 boys and girls found obese children and teens with abnormal cholesterol had thicker carotid arteries, the arteries in the neck that supply blood to the brain.
Thickened neck arteries are a sign of fatty buildup of plaque within the arteries feeding the heart muscle and brain.
The neck arteries in the obese children, aged 13 on average, "are looking like those of a 45-year-old," says Dr. Geetha Raghuveer, associate professor of pediatrics at the University of Missouri Kansas City school of medicine, and cardiologist at Children's Mercy Hospital.
Given the scope of the obesity crisis, the findings suggest a generation of children is at risk for premature cardiovascular disease.
"Kids almost never have heart attacks, no matter how high their risk may be," Raghuveer says. What's more, "I'm hoping they don't have hard calcified plaque like older adults. I'm very hopeful we may be able to reverse this process."
"But it is very possible that these kids -- especially the cohort of obese kids we've been seeing in the last decade or so -- may grow up to be young adults who may well have premature angina or heart attack, even as early as their 30s."
The children's "vascular age" surprised doctors in Canada.
"I thought they would be at increased risk, but I didn't think that it would be that bad," says Dr. Brian McCrindle, professor of pediatrics and staff cardiologist at Toronto's Hospital for Sick Children.
"We know that kids with cardiovascular risk factors and obesity have thicker lining to their carotid arteries than kids without those conditions," McCrindle says.
"What this study does is, it actually gives it an age."
Autopsy studies showed decades ago that fatty streaks and narrowing of the arteries can develop in the late teens and early 20s, says Dr. Geoff Ball, assistant professor in the department of pediatrics at the University of Alberta in Edmonton.
But the new study used ultrasound to detect subtle changes in the main arteries, he says. "These small changes are early steps in the genesis" of cardiovascular disease.
The study was small, and it's not clear if the ultrasounds are picking up early or advanced lesions.
But "it's one more piece of evidence that if we don't start taking this childhood obesity epidemic seriously, we're going to wind up with health problems that could potentially swamp the whole health-care system," McCrindle says.
In Canada, 18 per cent of children aged two to 17 are overweight, and another eight per cent -- an estimated 500,000 children -- are obese.
The new study, to be presented Wednesday at the American Heart Association's scientific sessions in New Orleans, involved 34 boys and 36 girls seen at a cardiology clinic.
All had risk factors such as obesity, abnormal levels of different types of cholesterol or a family history of premature cardiac death.
The children's vascular age -- the age at which their level of thickening would be normal -- was calculated by comparing their carotid artery thickness to that of 45-year-old matched for race and gender.
The researchers used a 45-year-old, because there is no data to compare them to normal, healthy children.
In what's being hailed as one of the grandest contributions to psychiatry since those of Sigmund Freud, a researcher at Simon Fraser University has published a groundbreaking theory that could change the scientific thinking about mental illness.
Bernard Crespi, an evolutionary biologist at SFU, has developed a theory -- with the help of Christopher Badcock, a sociologist at the London school of economics -- that suggests a "genetic tug of war" could be behind mental disorders such as autism and schizophrenia.
The theory, first published in Behavioural and Brain Sciences, suggests autism and schizophrenia are at opposite ends of a spectrum of mental disorders.
Each is an extreme outcome of a battle between the mother's and father's genes, which can steer brain development in one of two directions.
"Freud brought biology into psychiatry. I'm trying to bring evolutionary genetics into psychiatry," Crespi said Thursday in a phone interview.
Looking at the social behaviours of the two end-spectrum mental disorders, Crespi said they are solid opposites.
People with autism often have underdeveloped social behaviours, in that they often don't say much and avoid eye contact.
At the other end of the spectrum, people with schizophrenia are often hyper-developed in socialization, Crespi said.
Their sense of self can be hyper-developed into megalomania, language is hyper-developed into hearing voices, and, rather than feeling isolated, people with schizophrenia often feel as if they're being watched or plotted against.
Crespi said the theory could have significant implications for various therapies for mental disorders.
He suggests it makes sense to encourage behaviours that are found at the opposite end of the spectrum. So, in people with autism, it would make sense to nurture and strengthen their social behaviours. And the opposite might be true for people with schizophrenia.
"If you have somebody who's schizophrenic . . . by these ideas, what they've got is kind of an over-development of their social brain, if you will. And you basically want to encourage them to be less mentalistic, less over-interpreting with regard to sociality," he said. "You essentially want them to become relatively more autistic in the way they think about the world."
Crespi acknowledges that his way of thinking about treatment is drastically different than classical psychoanalysis -- where patients are asked to explore and examine their delusions -- but he is also aware that new ways of thinking are often controversial.
In an article earlier this week, the New York Times said Crespi and Badcock's "new idea provides psychiatry with perhaps its grandest working theory since Freud."
December 7, 2008
A Killer Without Borders
By NICHOLAS D. KRISTOF
As if you didn’t have enough to worry about ... consider the deadly, infectious and highly portable disease sitting in the lungs of a charming young man here, Garik Hakobyan. In effect, he’s a time bomb.
Mr. Hakobyan, 34, an artist, carries an ailment that stars in the nightmares of public health experts — XDR-TB, the scariest form of tuberculosis. It doesn’t respond to conventional treatments and is often incurable.
XDR-TB could spread to your neighborhood because it isn’t being aggressively addressed now, before it rages out of control. It’s being nurtured by global complacency.
When doctors here in Armenia said they would introduce me to XDR patients, I figured we would all be swathed in protective clothing and chat in muffled voices in a secure ward of a hospital. Instead, they simply led me outside to a public park, where Mr. Hakobyan sat on a bench with me.
“It’s pretty safe outside, because his coughs are dispersed,” one doctor explained, “but you wouldn’t want to be in a room or vehicle with him.” Then I asked Mr. Hakobyan how he had gotten to the park.
“A public bus,” he said.
He saw my look and added: “I have to take buses. I don’t have my own Lincoln Continental.” To his great credit, Mr. Hakobyan is trying to minimize his contact with others and doesn’t date, but he inevitably ends up mixing with people.
Afterward, I asked one of his doctors if Mr. Hakobyan could have spread his lethal infection to other bus passengers. “Yes,” she said thoughtfully. “There was one study that found that a single TB patient can infect 14 other people in the course of a single bus ride.”
Americans don’t think much about TB, just as we didn’t think much of AIDS in the 1980s. But drug-resistant TB is spreading — half a million cases a year already — and in a world connected by jet planes and constant flows of migrants and tourists, the risk is that our myopia will catch up with us.
Barack Obama’s administration should ensure it isn’t complacent about TB in the way that Ronald Reagan was about AIDS. Reagan didn’t let the word AIDS pass his lips publicly until he was into his second term, and this inattention allowed the disease to spread far more than necessary. That’s not a mistake the Obama administration should make with tuberculosis.
One-third of the world’s population is infected with TB, and some 1.5 million people die annually of it. That’s more than die of malaria or any infectious disease save AIDS.
“TB is a huge problem,” said Tadataka Yamada, president of global health programs for the Bill and Melinda Gates Foundation. “It’s a problem that in some ways has been suppressed. We often don’t talk about it.”
Ineffective treatment has led to multi-drug resistant forms, or MDR-TB. Scarier still is XDR-TB, which stands for extensively drug resistant TB. That is what Mr. Hakobyan has. There were only 83 cases of XDR-TB reported in the United States from 1993 to 2007, but it could strike with a vengeance.
“We always think we live in a protected world because of modern medicines and the like,” Dr. Yamada said. “But if we get a big problem with XDR, we could be in a situation like we had in the 19th century when we didn’t have good treatments.”
If we were facing an equivalent military threat capable of killing untold numbers of Americans, there might be presidential commissions and tens of billions of dollars in appropriations, not to mention magazine cover stories. But with public health threats, we all drop the ball.
Because of this complacency about TB, there hasn’t been enough investment in treatments and diagnostics, although some new medication is on the horizon.
“Amazingly, the most widely used TB diagnostic is a 19th-century one, and it’s as lousy as you might imagine,” said Dr. Paul Farmer, the Harvard public health expert whose Partners in Health organization was among the first to call attention to the dangers of drug-resistant TB.
In Armenia, the only program for drug-resistant TB, overseen by Doctors Without Borders, can accept only 15 percent of the patients who need it. And the drugs often are unable to help them.
“After two years of treatment with toxic drugs, less than half of such chronic TB patients are cured, and that’s very demoralizing,” noted Stobdan Kalon, the medical coordinator for Doctors Without Borders here. And anyone who thinks that drug-resistant TB will stay in places like Armenia is in denial. If it isn’t defused, Mr. Hakobyan’s XDR time bomb could send shrapnel flying into your neighborhood.
December 18, 2008
Miracle Tax Diet
By NICHOLAS D. KRISTOF
When the human body was evolving, almost the only things we drank were breast milk for the first few years and then water, water and more water.
It would obviously have been bad if we had evolved to feel full when water was sloshing about our stomachs because then we wouldn’t have eaten our fill the next time we speared a mastodon. Today, the unfortunate result is that if you drink a bottle of 7-Up, you still don’t feel full — the body treats the liquid as empty calories, like water — and so you won’t eat any less the next time you spear a Big Mac.
That has presented a huge problem in an age of sugary drinks, and some scholars believe they have become a major source of obesity. That’s why the new soda tax proposed by Gov. David Paterson of New York is such a breakthrough.
Mr. Paterson suggested the tax — an 18 percent sales tax on soft drinks and other nondiet sugary beverages — to help raise $400 million a year to plug a hole in the state budget. But it’s also a landmark effort that, if other states follow, could help make us healthier.
Let’s break for a quiz: What was the biggest health care breakthrough in the last 40 years in the United States? Heart bypasses? CAT scans and M.R.I.’s? New cancer treatments?
No, it was the cigarette tax. Every 10 percent price increase on cigarettes reduced sales by about 3 percent over all, and 7 percent among teenagers, according to the 2005 book “Prescription for a Healthy Nation.” Just the 1983 increase in the federal tax on cigarettes saved 40,000 lives per year.
In effect, the most promising cure for lung cancer didn’t emerge from a medical research lab but from money-grubbing politicians. Likewise, the best cure for obesity may turn out to be not a pill but a tax.
These days, sugary drinks are to American health roughly what tobacco was a generation ago. A tax would shift some consumers, especially kids, to diet drinks or water.
“Soft drinks are linked to diabetes and obesity in the way that tobacco is to lung cancer,” says Barry Popkin, a nutrition specialist at the University of North Carolina and author of the excellent new book, “The World Is Fat.” He warns that the cola industry will spend vast sums fighting the proposed tax.
One of industry’s objections is that soft drinks aren’t the only problem. That’s true, and I’d love to see a “Twinkie tax” as well. But evidence is accumulating that sugary drinks are a major contributor to obesity because of the evolutionary heritage I mentioned at the outset: Except for soups, liquid calories don’t register with the body, according to Professor Popkin and other specialists.
If you have a snack, even something unhealthy like potato chips, you’ll eat less at your next meal. But have a Coke, and despite all those calories, you’ll still eat just as much. Indeed, according to some studies, you’ll actually eat more.
“These findings raise the possibility that soft drinks increase hunger, decrease satiety or simply calibrate people to a high level of sweetness that generalizes to preferences in other foods,” said a peer-reviewed article last year in the American Journal of Public Health.
The average American consumes about 35 gallons of nondiet soda each year and gets far more added sugar from soda than from desserts.
Barack Obama has pledged to move toward a system of universal health coverage, and Democrats mostly see health care reform as a matter of providing access to doctors. Access and universal coverage are indeed essential, but there’s only so much doctors can do in this environment.
One priority must be a public health campaign to change social behavior. A starting point is to recognize that risky teen behavior these days can involve not just alcohol, drugs or sex but also extra-large Cokes.
One new study estimates that 24 million Americans now have diabetes, more than four times the number in 1980. The total direct and indirect cost to Americans is $218 billion each year — an average of $1,900 per American household. Each year, diabetes contributes to the deaths of more than 200,000 Americans.
Part of the solution must come from reforming agriculture so that we stop subsidizing corn that ends up as high fructose corn syrup inside soft drinks. Unfortunately, Mr. Obama on Wednesday chose Tom Vilsack, the former governor of Iowa who has longstanding ties to agribusiness interests, as agriculture secretary — his weakest selection so far.
The soft-drink industry will throw enormous resources into defeating the proposed New York tax on sugary drinks. We should stand behind Governor Paterson’s bold gesture. He is blazing a path that other states should follow.
Losing weight is never easy, but one of the most effective diets would start with a soft drink tax.
I invite you to visit my blog, On the Ground, and join me on Facebook. You can also watch my YouTube videos and follow me on Twitter.
December 23, 2008
The Price of Beauty
Some Hidden Choices in Breast Reconstruction
By NATASHA SINGER
For many cancer patients undergoing mastectomies, reconstructive breast surgery can seem like a first step to reclaiming their bodies.
But even as promising new operations are gaining traction at academic medical centers, plastic surgeons often fail to tell patients about them. One reason is that not all surgeons have trained to perform the latest procedures. Another reason is money: some complex surgeries are less profitable for doctors and hospitals, so they have less of an incentive to offer them, doctors say.
“It is clear that many reconstruction patients are not being given the full picture of their options,” said Diana Zuckerman, the president of the National Research Center for Women and Families, a nonprofit group in Washington.
One patient, Felicia Hodges, a 41-year-old magazine publisher in Newburgh, N.Y., chose a double mastectomy after she was found to have cancer of the right breast in 2004. She consulted a plastic surgeon, who offered her only reconstruction with breast implants, she said.
Ms. Hodges chose implants filled with saline, a procedure for which more than a third of reconstruction patients underwent a follow-up operation, studies show.
Ms. Hodges developed wound-healing problems that required her surgeon to remove her right implant, and she was left with a concave chest with a quarter-size hole in it, she said; she described the experience as “worse than the mastectomy.”
Then Ms. Hodges discovered a chat room on the patient-information Web site breastcancer.org, where women share detailed information about breast reconstruction beyond what they may have heard from their doctors.
Ms. Hodges learned of newer, more complex procedures that involve transplanting a wedge of fat and blood vessels from the abdomen or buttocks, which would be refashioned to form new breasts.
January 27, 2009, 7:32 pm
Eight Is Enough
By The Editors
A woman in Southern California has given birth to eight babies, the world’s second live-born set of octuplets. With advances in fertility treatment, multiple births are becoming more common, but how many are too many? What are the costs of delivering and caring for premature babies? And what about the emotional costs? We asked several experts to give us their thoughts.
Jeffrey Ecker, perinatologist
Felice J. Freyer, medical writer at The Providence Journal
Mark I. Evans, a doctor who specializes in reproductive genetic services
Ellie Tesher, the author of “The Dionnes”
It’s Not Easy
Jeffrey Ecker, an associate professor at Harvard Medical School, is an attending perinatologist at Massachusetts General Hospital.
It’s hard not to be excited about the birth of a baby. That’s especially true if you’re a patient who has had trouble becoming pregnant or a doctor taking care of such women. And yet, as a high-risk obstetrician, I find the news today that a woman in California has given birth to octuplets as much worrisome as happy.
To start there are potential problems for the newborns’ short and long-term health. Multiple gestations — twins, triplets and beyond — are almost always born premature. The average gestation of a single, uncomplicated pregnancy is 40 weeks. Twins average 36 weeks, triplets 33. Subtract two or three weeks for each additional fetus and it becomes obvious that most pregnancies of more than five (quintuplets and beyond) never make it to the point at which they can make survive outside the womb, which in spite of all our technologies seems fixed near 24 weeks of gestation.
“Premature multiples aren’t just small, they are sick.”
News reports indicate that this week’s octuplet pregnancy reached 30 weeks, and that is extraordinary, but even if many or all eight survive there are real and important concerns about their vision, lung, brain and other organ development. Increasingly we’re learning that prematurity is linked to cerebral palsy and learning disabilities. Premature multiples aren’t just small, they are sick.
Multiple pregnancies also raise concerns for the mothers’ health. Risks of high blood pressure and high blood sugar rise with increasing number of fetuses. And as the uterus grows so do the chances that the over-stretched womb will bleed during delivery. Treating the preterm labor that is inevitable requires medication, hospitalization and bed rest, which each bring the possibility of other complications. None of this is easy.
Finally, the news of the octuplets raises concerns regarding assisted reproduction. Many of us in this business view a higher-order multiple pregnancy like that which made news yesterday as a failure: a failure to regulate drugs and stimulation and thereby limit the number of gestations. Worries about both the mothers’ and the babies’ health is such that when triplets, quads and beyond arise, doctors discuss the option of fetal reduction: stopping the heart beats of some number of fetuses to improve the chances for those that remain. To be sure, reduction will seem wrong to some patients and no one could ever require that someone follow such a path. All this, especially for those for whom reduction is not an option, argues for a careful and considered discussion up front, before medications are given and the process begun. Better to cancel a cycle of stimulation or in vitro fertilization and start again than risk over-stimulation and the octuplets that can result.
So today we will hope for the continued good health of this California mother and her babies. But we will also hope that such cases only rarely — maybe never — happen again.
The Price of Love
Felice J. Freyer is the medical writer at The Providence Journal. She was a 2007 media fellow with the Kaiser Family Foundation, exploring the effects of premature births on families and society.
As astonishing as their birth may be, the biggest challenges for the California octuplets still lie ahead. Like the more than half-million babies who are born prematurely in the United States each year, they will probably spend weeks in intensive care and go home with continuing medical needs.
Who will pay for it? In 2001, hospital costs for preterm and low-birth-weight babies (according to a recent analysis in the journal Pediatrics) totaled $5.8 billion. For babies with the greatest needs –– those born before 28 weeks gestation –– the cost of an average hospital stay was $65,600. Multiply that by eight.
“For babies with the greatest needs –– those born before 28 weeks gestation –– the cost of an average hospital stay was $65,600. Multiply that by eight.”
If the octuplets’ parents have private health insurance, they may quickly reach the lifetime limit of their coverage. Or their employer may find health insurance rates soaring out of reach for their co-workers. If the parents don’t have coverage, or they don’t have enough coverage, the state Medicaid program or the hospital’s charity-care program could pick up the difference. Either way, others will pay, through higher premiums or higher taxes.
The hospital costs are just the beginning, though. Premature babies are at risk for all kinds of physical and emotional problems. The Institute of Medicine estimated that in 2005 premature births cost American society $26.2 billion in medical care, early intervention services for preschoolers, special education for disabled children and lost productivity. But the institute’s calculations took into account only the first few years of the child’s life. Many premature babies have lasting problems, and no one has added up what they cost.
If the octuplets are among the lucky ones, they will overcome their obstacles and go on to live happy, productive lives. I’ve met young adults, born severely premature, who are now attending college, free of deficits. Even for those coping with disability, it seems callous to talk about the dollars required to raise them to their fullest potential. Surely, they deserve no less. And I’ve yet to meet a parent who was sorry a premature child survived. That’s the fundamental question our society faces concerning premature births. We admire the power of parental love. We marvel at what medical technology can accomplish. But we pay a price.
Mark I. Evans, the director of a program that provides reproductive genetics services, is president of the Fetal Medicine Foundation of America and professor of obstetrics and gynecology at the Mount Sinai School of Medicine.
For more than 20 years, there has been periodic national news media attention to the birth of quintuplets, then sextuplets, septuplets and now octuplets. Quadruplets don’t even make the local news anymore. The birth rate of twins in the United States has more than doubled.
Overlooked in the “happy news” of these births are the troubling vast increases in neonatal deaths, handicaps and other long-term problems that even follow-up visits by the news media have mostly glossed over.
Since the 1980s, a small number of experienced doctors have developed considerable experience in improving the outcomes in higher-order multiple pregnancies. This is accomplished — usually at about three months of gestation — by reducing the number of fetuses to a manageable number, usually to two. Data from literally thousands of cases over the last 20 years show conclusively that if one defines “success” as a healthy mother and a healthy family then with multiples fewer is always safer.
In the 1980s, the majority of patients with higher-order multiples (more than three) were patients who became pregnant by medication alone. Now, in vitro fertilization makes up the majority of cases. Half of all pregnancies involving in vitro fertilization are twins or more. With the limitation on the number of embryos transferred, the number of very higher-order multiples like octuplets has gone down but realistically will never be zero. Also, concomitant with increasing use of donor eggs, the proportion of women with multiples over age 40 has gone from about 1 percent of the patients we see to about 15 percent.
Over the years, the outcomes of patients having reductions have improved considerably. Now, a woman with a quadruplet pregnancy who has about a 25 percent chance of losing all the fetuses if she tries to carry the four, can decrease the loss rate to about 5 percent by reducing to twins. For triplets, the rate goes down to 3 percent to 4 percent from 15 percent. Prematurity and its resultant complications are likewise drastically reduced. The cerebral palsy rate for a triplet baby is about 1 in 30, for a twin 1 in 100, and for a singleton 1 in 700.
Since more than half of in vitro fertilization patients are over 35, the genetic issues are paramount. A 35-year-old has a 1 in 190 risk of having a baby with a chromosome abnormality with a singleton. In my program for about 80 percent of the patients, we perform genetic diagnosis the day before the reduction.
Reduction will always be controversial. But except for the most conservative doctors, almost all parties at the beginning of the experience in the 1980’s believed that with quadruplets or more, the risks of continuing were so astronomical, that reductions were an improvement. No one believed then that twins should be reduced to a singleton; the debate was with triplets. Over the years, the data have shown, however, that triplets reduced to twins (or now to a singleton) do far better than unreduced cases in terms of pregnancy loss and complications of prematurity. In fact, now for the woman who starts with twins — again defining success as a healthy mother and family — it is safer to reduce to a singleton than keep the twins. The improvement of two to one is real but certainly not as significant as, say, seven to two. Only a small percentage of women with twins reduce, but it can be helpful in the appropriate situations.
Reduction is not abortion. It does not end a pregnancy. Furthermore, a woman has an abortion because she wants — for whatever reason — to end a pregnancy. Women have reductions because it may be the best way or sometimes the only way in which to maximize the chance of having a healthy family.
Remember the Dionne Quintuplets
Ellie Tesher, an internationally syndicated advice columnist, is the author of “The Dionnes,” an account of the struggles of the Dionne quintuplets.
It would be a shame if the California octuplets’ family, or the public, permits a prolonged news media circus for these children, once the immediate happy news of their safe birth and health status is past. Though the parents may be warmed by the public’s enthusiasm and initially need help managing eight babies, it can be equally harmful to allow their children to become a continued source of income through public exposure.
These were the tough lessons from the experience of the Canadian-born Dionne quintuplets — the first quintuplets ever in the world to survive to adulthood. Their celebrity took a terrible emotional toll on the quintuplets. Born in 1934, the five identical Dionne girls were objectified in a public feeding frenzy that went on for nine years.
Millions of American tourists alone — including Hollywood movie stars — traveled to Quintland, in northern Ontario, a theme park set up where the girls lived in a hospital setting and they could be viewed “performing” in repeated daily showings. The Dionnes brought in millions of dollars to government coffers and enriched officially appointed hangers-on.
Their celebrity alienated the quintuplets by age 9 from the rest of their family, and to this day they are expected to provide largess to others. In the end, with only one another to trust, they found it almost impossible to maintain other adult relationships.
I know personally that the surviving quintuplets, Cecile and Annette, if asked today, would advise that everyone look at these adorable babies as individuals and treat them — and yes, even dress them — to suit their own unique personalities.
You may think that, with the prevalence of fertility treatments and greater awareness of multiple births today, that the Dionne experience could not happen again. But we only have to look at the news media attention that surrounds current celebrities, the fame-seeking syndrome it has produced, along with the anticipation of retail advertisers and the fact that these infants are already headliners, to know that the California octuplets could face some of the same heartbreak that the Dionnes did.
Calgary HeraldWhen Ranjit Hayer, the 60-year-old woman who has given birth to twins, was turned down as a candidate for in vitro fertilization in Canada, she refused to take no for an answer.
Instead, she went to India, where doc-tors used in vitro to successfully implant donor eggs.
But just because something can be done, doesn't mean that it should be done, say experts who are weighing in on the situation.
"My initial reaction was, 'Oh my goodness. This is somebody who's post-menopausal and having a baby. It goes against nature,'" says Dr. Glenys Godlovitch, the acting director for the University of Calgary's Office of Medical Bioethics and an associate professor in the Department of Community Health Sciences in the University of Calgary's faculty of medicine.
Presumably, Canadian doctors turned Hayer down in the first place because of her age and the high-risk pregnancy that would ensue.
Despite Godlovitch's first reaction, she stresses this is a complicated issue, and one that should not be judged based on quick assessments.
We do not know the details regarding family, cultural and community support, she says.
"I've not decided one way or the other whether I think it's absolutely right or absolutely wrong,"she says. "We need to think more broadly about the relationship between what is clinically possible and what is overall appropriate."
The confusion between what can and should be done in the medical world is an often-debated topic, especially in the field of assisted reproduction, which is governed mostly by voluntary norms in Canada.
Dr. Paul Claman, president of the Ottawa Fertility Centre, says his clinic will offer egg donation to women up to the age of 49 -- a widely used cut-off age in Canada.
Beyond that age, he believes it would be "medically cavalier" to impregnate a woman in her 50s, because of the cardiovascular risks involved.
"And there are even more serious social issues," he says. "If you have a young child and you're in your 70s, who's going to take care of this child if you suffer a disability or worse?"
Calgary Bishop Fred Henry makes the same case.
"Is it fair to the children that they be raised by a 75-year-old, unless it's a case of absolute necessity?"
Henry believes in vitro fertilization should not ever be used, and especially not for women past the natural childbearing age.
"This is one of those situations where technology is going too far," he says.
Juliet Guichon, an academic lawyer and senior associate also with theUof C's bioethics office, says that Hayer's boys will face many challenges.
Depending on who donated the eggs and whether she stays connected to the family, the kids may not ever know much of their medical history.
And because they were born prematurely, she says, they may face health problems.
Socially, they will have to deal with parents who will be very different from those of kids their own age.
But it's not only the twins' well-being that concerns Guichon.
Faced with her recovery from giving birth, breastfeeding and the stress of delivering prematurely, Hayer also has a tough road ahead, she says.
"There are lots of problems that this situation presents. Some are in the short run and some are in the long run," says Guichon.
"Having said all that, here's this woman who's thrilled. She's living her dream. So, I mean, in a way you can't help but be happy for her."
Some Of The World's Oldest Mothers - Jan. 2009: A 60-year-old Calgary woman, Ranjit Hayer, delivers twins at Foothills Hospital. - Nov. 2008: An Indian woman, Rajo Devi, delivers her first child, a daughter, at age 70. - Dec. 2006: A 67-year-old Spanish woman gives birth to twins in Barcelona. - July 2006: Patricia Rashbrook, 62, gives birth to a son and becomes the oldest woman to give birth in the United Kingdom. - Jan. 2005: A 67-year-old Romanian woman, Adriana Illiescu, gives birth to a baby daughter. - June 2001: A French woman, Jeanine S., 62, gives birth to a son, becoming France's first "grandma mom."
Neem tree offers shade, medicine, and insect control
By Reese Halter, Calgary HeraldFebruary 8, 2009
Of the more than 80,000 tree species on our planet, the Indian neem tree (Azadirachta indica) is magnificent and known by millions of people as "the village pharmacy."
Imagine one kind of tree that offers medicine, cosmetics, rope, tea, glue, wood, fertilizer, pesticides and insecticides, lubricant, lighting and heating oil, veterinary medicine and shade. Welcome to the neem tree.
Neem is native to India and Myanmar. It grows from the southern Indian tip of Karalla to the Himalayan hills. It spans both tropical and subtropical latitudes, from wet tropical to semi-arid regions and from sea level to 700 metres elevation. It does not tolerate cold temperatures or saturated soils.
These evergreen beauties can easily reach 30 metres in height with impressive regal crowns and 2.5-metre girths. They are very fast-growing and are able to recolonize denuded and infertile soils.
Their profuse white mellifluous flowers bear fruit that at first glance resembles an olive.
The fruits have a sweet pulp that is an important source of food for birds, bats and baboons. A hard shell encases seeds known as a kernel --sometimes there are as many as three kernels in each fruit. Young saplings produce fruit by the age of four and a 10-year-old tree can yield up to 50 kilograms of fruit.
The neem tree can easily live for more than two centuries. And there are over 20 million neem trees in India alone.
Neem has been introduced to over 30 countries around the globe including the United States, in Arizona, California, Florida and Hawaii.
Neem is particularly important in the developing world. It provides shade throughout the year and only in extreme droughts does it shed its leaves. Neem plantations provide employment and help generate income in rural communities.
Ground-up kernels provide oil for lighting and heat for cooking. The oil is also used as a lubricant for greasing cart wheels. The solid material left after making oil--known as cake -- is spread over the fields, adding essential organic matter and enriching the soil. In addition, the cake acts very effectively at repelling crop-destroying root and stem sucking nematodes.
Moreover, the developing world is using the tremendous ability of neems to successfully combat encroaching desertification, deforestation and rising greenhouse gases.
For three thousand years the Indian Ayurveda shamans have known of neems' potent insecticide, pesticide and medicinal properties.
The neem tree's remarkable defence belongs to a class of compounds called triterpenes, more specifically limonoids. At least nine of these limonoids block insect growth.
Azadirachtin is neem's main defence. It blocks and disrupts growth and reproduction of insects. Both meliantriol and salannin are efficacious insect feeding inhibitors.
Extracts of neem are effective against at least 200 different insect species including locust, mosquitoes carrying malaria and voracious Australian blowflies.
Neem residue can be sprinkled on the soil, taken up by plant roots and used by crops as a plant defence mechanism, for up to 10 weeks against insect infestations. There is no trace of neem residue in crops. Furthermore, neither pollinators such as bees, moths and bats nor beneficial insects such as spiders, ladybugs and dragonflies are harmed by neem extracts.
All known warm-blooded animals and birds are also safe from harm.
Azatin, Align and Margosan-O are all neem-based products that protect crops.
Neem extract is an excellent general antiseptic, successful against a variety of skin disease, septic sores and infected burns. The leaves--applied in a paste--are used to treat boils, ulcers and eczema.
Neem is very effective at fighting Trichophyton fungus or athlete's foot.
As an antibacterial, neem extract is nature's weapon against Staphylococcus aureus.
Neem extract provides millions of impoverished people with low-cost pain relief as an analgesic and as an antipyretic or fever-reducer.
Interestingly, neem extract is being used to immunize insects carrying the parasite (Trypanosoma cruzi) causing Chagas' Disease, which has crippled more than 20 million people in Latin America.
Each day in India, millions of people break off a neem twig and use it as a toothbrush. Compounds in the neem bark have strong antiseptic properties and prevent tooth decay as well as preventing and healing inflammation in gums. A number of companies now offer neem toothpaste and mouthwashes.
Veterinarians use crushed neem leaves applied to open wounds on cattle to eliminate maggots. They regularly use neem oil to repel blowflies, and azqadirachtin to prevent biting and horn flies.
The list of beneficial products from the neem tree is astonishing. They include wonderful facial and body creams, soaps, nail polishes, furniture, cricket bats, cabinetry, flooring, waxes, dyes, prized honey and soon-to-be food additives.
Neem is truly one of Mother Nature's most remarkable trees.
Dr. reese halTer is a naTuralisT anD founDer of The inTernaTional
conservaTion insTiTuTe global foresT science. he can be conTacTeD
February 10, 2009
In Matters of the Heart, Luck Can Make All the Difference
By JAY NEUGEBOREN
For the past 10 years I’ve celebrated Valentine’s Day two days early, because it was on Feb. 12, 1999, that my life — and my heart — was given back to me.
Although I had no conventional risk factors or symptoms, it turned out that two of my three major coronary arteries were 100 percent blocked, the third 90 percent. And so it was that three months short of my 61st birthday, I underwent a six-and-a-half-hour quintuple-bypass operation at Yale University Hospital.
I was back at work in a few weeks and have had no heart problems since. Now nearing 71, I swim three-quarters of a mile most days and play singles tennis (and sometimes win) against players decades younger than I am. And a year ago, after 20 years of bachelorhood, much of it as single parent to my three children, I married again.
How, nearly dead a decade ago, did I get so lucky?
In the aftermath of the revelation last year that Merck and Schering-Plough had been sitting on results of a failed clinical trial of a new cholesterol-lowering drug, an editorial in The New York Times noted that the trial’s findings “raise doubts about the current belief that cholesterol is the key to cardiovascular health.” Based on my experience, I would suggest that these doubts have been with us for a long time.
Newspapers, magazines, television shows, medical journals and — especially — drug company advertisements all reinforce the notion that lowering cholesterol will prevent heart disease and save your life. Friends regularly call to report their latest cholesterol scores, as if they are somehow gaining ground on the Angel of Death.
But cholesterol, as I’ve learned, is only a small part of the story. If you combine all known risk factors — high cholesterol, high blood pressure, smoking, genetics, obesity, lack of exercise — the combination still accounts for fewer than half the instances of heart disease. Conversely, as in my case, when none of these factors apply, one can still be days or hours away from cardiac death.
In addition, two doctors who examined me, including a cardiologist, saw no urgency in my condition. It remained for a lifelong friend, another cardiologist, to get the diagnosis right, and this by phone from 3,000 miles away.
When I told him I was concerned about occasional shortness of breath while swimming, and about an intermittent burning sensation in my back, he told me to get to a hospital as soon as possible. Why? Because he knew me, because he listened to me carefully and because he could place my new symptoms in the context of my overall story.
And so I went to a hospital where another lifelong friend, a physician at Yale, saw that I received immediate treatment. The fact that I was privileged — not only to have these doctors as friends, but also to have health insurance that allowed me to receive treatment anywhere and by any doctor — is what saved my life.
I had, that is, what many Americans do not have: access to the best and most timely medical care available.
To get diagnoses and treatment plans right, we need doctors who know us over time, and who have the time to know us. For just as every medication reacts differently in every patient, so too does the meaning of every test result vary with every patient. Paradoxically, the better tests are, the more we need the judgment of doctors to sort out the results and to come up with the right treatments.
We now have technologies to treat virtually all cardiovascular problems, and to save lives we were previously helpless to save. But what many of us do not have is access to these technologies and to doctors who know how to use them.
President George W. Bush famously said that all Americans, even the tens of millions without health insurance, can get health care by going to emergency rooms. Perhaps. But clearly the doctors one meets there have neither the time nor the knowledge — of specific illnesses or of individual patients — to provide anything resembling the best care.
Clearly, too, people are not going to get the best care when given limited choices. A recent New York State survey, for example, revealed that most cardiologists said that they sometimes did not operate on patients who might benefit from surgery because of their concerns about hurting their rankings on state-mandated physician scorecards.
And even when people have health insurance, their doctors are all too likely to change from year to year, and even visit to visit. So doctors and patients often wind up at severe, sometimes life-threatening disadvantages when it comes to formulating accurate diagnoses and effective treatment plans.
Why do some people who smoke and drink at will, eat whatever they want and never exercise live to a ripe old age, while others who follow all the rules are sometimes cut down in their prime? We don’t know. What we do know is that gross inequities in our health care system prevail, that the quality of health care varies enormously depending primarily upon one’s job and income, and that luck can make an enormous difference.
I was lucky to have grown up with friends who became doctors, and I was lucky to live in a time when my life could be saved. “Twenty or so years ago,” my heart surgeon said to me, “I couldn’t have done anything for you.”
And I was lucky to live long enough to fall in love and marry again, at an age when many have given up any such hope. So this year I’ll celebrate two Valentine’s Days: one on Feb. 12, in gratitude for the heart given back to me a decade ago, and the other on Feb. 14, when my wish for others will be that they might be as lucky, in matters of the heart, as I’ve been.
Jay Neugeboren is the author, most recently, of the novel “1940.”
February 17, 2009
Picture Emerging on Genetic Risks of IVF
By GINA KOLATA
Over the past 30 years, in vitro fertilization has been reassuringly safe. Millions of healthy children have been born and developed normally. And the first IVF baby, Louise Brown, born in England on July 25, 1978, now has her own child, 2-year-old Cameron, conceived without the technique.
But researchers have always wondered whether there might be subtle changes in an embryo that is grown for several days in a petri dish, as IVF embryos are — and, if so, whether would there be any consequences.
Now, with new epidemiological studies and new techniques that allow scientists to probe the genes of embryo cells, some tentative answers are starting to emerge.
The issues have nothing to do with the chances that a woman will have twins, triplets or even, as just happened in California, octuplets. Instead, they involve questions of whether there are changes in gene expression or in developmental patterns, which may or may not be obvious at birth.
For example, some studies indicate that there may be some abnormal patterns of gene expression associated with IVF and a possible increase in rare but devastating genetic disorders that appear to be directly linked to those unusual gene expression patterns. There also appears to be an increased risk of premature birth and of babies with low birth weight for their gestational age.
In November, the Centers for Disease Control and Prevention published a paper reporting that babies conceived with IVF, or with a technique in which sperm are injected directly into eggs, have a slightly increased risk of several birth defects, including a hole between the two chambers of the heart, a cleft lip or palate, an improperly developed esophagus and a malformed rectum. The study involved 9,584 babies with birth defects and 4,792 babies without. Among the mothers of babies without birth defects, 1.1 percent had used IVF or related methods, compared with 2.4 percent of mothers of babies with birth defects.
The findings are considered preliminary, and researchers say they believe IVF does not carry excessive risks. There is a 3 percent chance that any given baby will have a birth defect.
But the real question — what is the chance that an IVF baby will have a birth defect? — has not been definitively answered. That would require a large, rigorous study that followed these babies. The C.D.C. study provides comparative risks but not absolute risks.
Yet even though the risks appear to be small, researchers who are studying the molecular biology of embryos grown in petri dishes say they would like a better understanding of what happens, so they can improve the procedure and allow couples to make more informed decisions.
“There is a growing consensus in the clinical community that there are risks,” said Richard M. Schultz, associate dean for the natural sciences at the University of Pennsylvania. “It is now incumbent on us to figure out what are the risks and whether we can do things to minimize the risks.”
And although the questions are well known, the discussion has been largely confined to scientists, said Dr. Elizabeth Ginsburg, president of the Society for Assisted Reproductive Technology.
Dr. Ginsburg, who is the medical director of in vitro fertilization at Brigham and Women’s Hospital in Boston, says her center’s consent forms mention that there might be an increased risk for certain rare genetic disorders. But, she says, none of her patients have been dissuaded.
Richard G. Rawlins, who directs the in vitro fertilization and assisted reproduction laboratories at the Rush Centers for Advanced Reproductive Care in Chicago, said that when he spoke to patients he never heard questions about growing embryos in the laboratory and the possible consequences.
“I have never had a patient ask me anything” about it, he said, adding, “For that matter, not many doctors have ever asked, either.”
Dr. Andrew Feinberg, a professor of medicine and genetics at Johns Hopkins, became concerned about the lack of information about IVF eight years ago when he and a colleague, Dr. Michael R. DeBaun, were studying changes in gene expression that can lead to cancer.
Their focus was on children with Beckwith-Wiedemann syndrome, characterized by a 15 percent risk of childhood cancers of the kidney, liver or muscle; an overgrowth of cells in the kidney and other tissues; and other possible abnormalities, among them a large tongue, abdominal-wall defects and low levels of blood sugar in infancy.
The syndrome, Dr. Feinberg and Dr. DeBaun found, was often caused by changes in the expression of a cluster of genes, and those changes also are found in colon and lung cancers. Children with those gene alterations had a 50 percent risk of the childhood cancers. The normal risk is less than 1 in 10,000.
The two investigators recruited children with the disorder, following them and studying them in their clinic. Then, several mothers in the study who had had IVF asked the researchers: Was it possible that the fertility treatments had caused Beckwith-Wiedemann syndrome?
That prompted Dr. Feinberg and Dr. DeBaun to investigate the prevalence of IVF and related methods in the pregnancies that resulted in children with Beckwith-Wiedemann syndrome. Their conclusion, and the conclusion from at least half a dozen other large studies, was that there were about 10 times more parents who had used IVF or related methods than would be expected.
Another disorder caused by abnormal gene expression, Angelman syndrome, also is suspected of being linked to IVF. It involves severe mental retardation, motor defects, an inability to speak and a cheerful disposition. The disorders are rare. Beckwith-Wiedemann occurs just once in 13,000 children, and Angelman occurs about once in every 10,000 children.
Why, researchers ask, would growing embryos in petri dishes elicit changes in gene expression? And if there are changes, could they alter the laboratory conditions so those gene expression changes do not occur?
One place to look might be the broth, known as the culture medium, in which embryos grow. From the start of IVF, scientists knew that the composition of the broth affected how quickly embryos grew, Dr. Rawlins said. And they knew that embryos, both animal and human, grew much more slowly in the lab than they did in the body.
One thing the culture medium provides is chemicals that can be used to add methyl groups to genes. The presence, or absence, of the methyl groups can control whether genes are active or not, a process known as epigenetics. Epigenetic changes not only cause rare disorders like Beckwith-Wiedemann syndrome but also are associated with low-birth-weight babies and an increased risk of a variety of cancers. That does not mean that growing embryos in petri dishes will have such effects, but it does raise questions about what is known about the procedure.
Dr. George Daley, a researcher at Harvard Medical School studying human embryonic stem cells, said the questions also extended to those cells, which are taken from human embryos and grown in petri dishes. He has seen epigenetic changes in stem cells but is not sure what they mean.
“My major concern is that we don’t have enough information, or the tools to measure epigenetic stability,” he said. “It may or may not be relevant to the safety of the cells, though I suspect it is.”
But figuring out what, if anything, in the culture medium might adversely affect embryo growth and development may not be easy, Dr. Feinberg said.
Dr. Ginsburg said the Society for Assisted Reproductive Technology discussed whether to ask IVF centers to report what media they were using to grow their embryos. But, she said, “programs use multiple media, and it is very common for programs to switch from one media to another.”
If mouse embryos are even close to reflecting what can happen with humans, then there is no question that gene expression can be altered by growing embryos in a laboratory, Dr. Schultz says.
He and several others spent years asking whether there were gene expression changes in mouse embryos that are grown in the laboratory — there are — and whether they could see behavioral changes in the animals. They did.
For example, the investigators gave mice a test that required remembering the location of a platform hidden by opaque water. The IVF mice had no trouble learning where the platform was, but were more likely to forget what they had learned, Dr. Schultz found.
In another test, which measured a fear response when mice are in the open, IVF mice lacked the normal caution and fear that non-IVF mice are born with.
“They are changes,” Dr. Schultz said, of the test results. “And the only difference is that they were cultured,” meaning that the mice started out as embryos in a petri dish.
Along with the behavioral changes were changes in the methylation of genes — epigenetic changes, Dr. Schultz reports. “I am suspicious that manipulation and culturing of embryos is a contributing factor,” he adds.
But following babies born after IVF or intracytoplasmic sperm injection is not easy. And if problems emerge from epigenetic changes, they may not be apparent until adulthood or middle or old age.
“When you send questionnaires, the tendency is for the couple who may have had a problem or who think they have a problem to answer that questionnaire,” said Dr. Zev Rosenwaks, director of the Center for Reproductive Medicine and Infertility at New York Weill Cornell Center. Those who do not respond tend to be parents whose children seem fine, skewing the data.
Dr. Rosenwaks’s group largely paid for its own studies. They conclude, he said, that “even if there was a slight increase in abnormalities, the rate was not much higher than in the general population.”
Others, like Dr. Alistair Sutcliffe of University College London, say the field is crying out for more information on the risks.
“I talk on this topic worldwide,” he said. “My talks over time are based on the known literature. And I have gradually become slightly less optimistic about the things that are known about the health of the children” born after IVF and related procedures.
“Obviously, more knowledge is required,” Dr. Sutcliffe said. “The perfect study hasn’t been done.”
February 17, 2009
Vitamin Pills: A False Hope?
By TARA PARKER-POPE
Ever since the Nobel Prize-winning biochemist Linus Pauling first promoted “megadoses” of essential nutrients 40 years ago, Americans have been devoted to their vitamins. Today about half of all adults use some form of dietary supplement, at a cost of $23 billion a year.
But are vitamins worth it? In the past few years, several high-quality studies have failed to show that extra vitamins, at least in pill form, help prevent chronic disease or prolong life.
The latest news came last week after researchers in the Women’s Health Initiative study tracked eight years of multivitamin use among more than 161,000 older women. Despite earlier findings suggesting that multivitamins might lower the risk for heart disease and certain cancers, the study, published in The Archives of Internal Medicine, found no such benefit.
Last year, a study that tracked almost 15,000 male physicians for a decade reported no differences in cancer or heart disease rates among those using vitamins E and C compared with those taking a placebo. And in October, a study of 35,000 men dashed hopes that high doses of vitamin E and selenium could lower the risk of prostate cancer.
Of course, consumers are regularly subjected to conflicting reports and claims about the benefits of vitamins, and they seem undeterred by the news — to the dismay of some experts.
“I’m puzzled why the public in general ignores the results of well-done trials,” said Dr. Eric Klein, national study coordinator for the prostate cancer trial and chairman of the Cleveland Clinic’s Glickman Urological and Kidney Institute. “The public’s belief in the benefits of vitamins and nutrients is not supported by the available scientific data.”
Everyone needs vitamins, which are essential nutrients that the body can’t produce on its own. Inadequate vitamin C leads to scurvy, for instance, and a lack of vitamin D can cause rickets.
But a balanced diet typically provides an adequate level of these nutrients, and today many popular foods are fortified with extra vitamins and minerals. As a result, diseases caused by nutrient deficiency are rare in the United States.
In any event, most major vitamin studies in recent years have focused not on deficiencies but on whether high doses of vitamins can prevent or treat a host of chronic illnesses. While people who eat lots of nutrient-rich fruits and vegetables have long been known to have lower rates of heart disease and cancer, it hasn’t been clear whether ingesting high doses of those same nutrients in pill form results in a similar benefit.
In January, an editorial in The Journal of the National Cancer Institute noted that most trials had shown no cancer benefits from vitamins — with a few exceptions, like a finding that calcium appeared to lower the recurrence of precancerous colon polyps by 15 percent.
But some vitamin studies have also shown unexpected harm, like higher lung cancer rates in two studies of beta carotene use. Another study suggested a higher risk of precancerous polyps among users of folic acid compared with those in a placebo group.
In 2007, The Journal of the American Medical Association reviewed mortality rates in randomized trials of antioxidant supplements. In 47 trials of 181,000 participants, the rate was 5 percent higher among the antioxidant users. The main culprits were vitamin A, beta carotene and vitamin E; vitamin C and selenium seemed to have no meaningful effect.
“We call them essential nutrients because they are,” said Marian L. Neuhouser, an associate member in cancer prevention at the Fred Hutchinson Cancer Research Center in Seattle. “But there has been a leap into thinking that vitamins and minerals can prevent anything from fatigue to cancer to Alzheimer’s. That’s where the science didn’t pan out.”
Everyone is struggling to make sense of the conflicting data, said Andrew Shao, vice president for scientific and regulatory affairs at the Council for Responsible Nutrition, a vitamin industry trade group. Consumers and researchers need to “redefine our expectations for these nutrients,” he said. “They aren’t magic bullets.”
Part of the problem, he said, may stem from an inherent flaw in the way vitamins are studied. With drugs, the gold standard for research is a randomized clinical trial in which some patients take a drug and others a placebo. But vitamins are essential nutrients that people ingest in their daily diets; there is no way to withhold them altogether from research subjects.
Vitamins given in high doses may also have effects that science is only beginning to understand. In a test tube, cancer cells gobble up vitamin C, and studies have shown far higher levels of vitamin C in tumor cells than are found in normal tissue.
The selling point of antioxidant vitamins is that they mop up free radicals, the damaging molecular fragments linked to aging and disease. But some free radicals are essential to proper immune function, and wiping them out may inadvertently cause harm.
In a study at the University of North Carolina, mice with brain cancer were given both normal and vitamin-depleted diets. The ones who were deprived of antioxidants had smaller tumors, and 20 percent of the tumor cells were undergoing a type of cell death called apoptosis, which is fueled by free radicals. In the fully nourished mice, only 3 percent of tumor cells were dying.
“Most antioxidants are also pro-oxidants,” said Dr. Peter H. Gann, professor and director of research in the department of pathology at the University of Illinois at Chicago. “In the right context and the right dose, they may be able to cause problems rather than prevent them.”
Scientists suspect that the benefits of a healthful diet come from eating the whole fruit or vegetable, not just the individual vitamins found in it. “There may not be a single component of broccoli or green leafy vegetables that is responsible for the health benefits,” Dr. Gann said. “Why are we taking a reductionist approach and plucking out one or two chemicals given in isolation?”
Even so, some individual vitamin research is continuing. Scientists are beginning to study whether high doses of whole-food extracts can replicate the benefits of a vegetable-rich diet. And Harvard researchers are planning to study whether higher doses of vitamin D in 20,000 men and women can lower risk for cancer and other chronic diseases.
“Vitamin D looks really promising,” said Dr. JoAnn E. Manson, the chief of preventive medicine at Brigham and Women’s Hospital and an investigator on several Harvard vitamin studies. “But we need to learn the lessons from the past. We should wait for large-scale clinical trials before jumping on the vitamin bandwagon and taking high doses.”
By Sarah Schmidt, Canwest News ServiceMarch 17, 2009 3:01 AM
An international group of scientists is calling on Canada and other countries to bring in tougher safety standards for cellphone use after a Swedish team found a fivefold elevated risk of malignant brain tumours in children who begin using mobile phones before the age of 20.
The plea--and the science underlying it--is published in the forthcoming edition of Pathophysiology, devoted to peer-reviewed research about the biological effects of the global explosion of wireless technologies and devices like cellphones, cordless phones, wireless Internet and cell towers.
The findings of 15 studies from health researchers in six different countries, looking at the effects of electromagnetic fields and radio frequency radiation on living cells and on the health of humans, should jolt government agencies into action as a precautionary mea-sure, Dr. David Carpenter, director of the Institute for Health&the Environment at the University at Albany, and one of the co-authors, said in an interview.
"What stands out is the consistency of the association of exposure and disease. The evidence, as I see it, is sufficiently strong that there needs to be public warnings, there needs to be establishments of exposure guidelines and that the present guidelines -- in Canada, the United States or anyone else--are not protective of human health.
"I see us facing a major problem in the future because of the fact that young children are on cellphones constantly, and we may be setting ourselves up for an epidemic of brain cancer, the same thing we did with cigarette smoking and lung cancer."
According to Columbia University physiology professor Martin Blank, who edited the special issue, the laboratory studies "point to significant interactions" of both power frequency and radio frequency with cellular components, especially DNA.
The epidemiological studies "point to increased risk" of developing certain cancers associated
with long-term exposure to radio frequency, he said.
Dr. Lennart Hardell is among the scientists who contributed to the special edition of the journal. The oncologist from Sweden's University Hospital found that after one or more years of cellphone use, there is a 5.2-fold elevated risk of malignant brain tumour in children who begin using mobile phones before the age of 20 years; the odds for other ages was 1.4.
March 19, 2009
Prostate Test Found to Save Few Lives
By GINA KOLATA
The PSA blood test, used to screen for prostate cancer, saves few lives and leads to risky and unnecessary treatments for large numbers of men, two large studies have found.
The findings, the first based on rigorous, randomized studies, confirm some longstanding concerns about the wisdom of widespread prostate cancer screening. Although the studies are continuing, results so far are considered significant and the most definitive to date.
The PSA test, which measures a protein released by prostate cells, does what it is supposed to do — indicates a cancer might be present, leading to biopsies to determine if there is a tumor. But it has been difficult to know whether finding prostate cancer early saves lives. Most of the cancers tend to grow very slowly and are never a threat and, with the faster-growing ones, even early diagnosis might be too late.
The studies — one in Europe and the other in the United States — are “some of the most important studies in the history of men’s health,” said Dr. Otis Brawley, the chief medical officer of the American Cancer Society.
In the European study, 48 men were told they had prostate cancer and needlessly treated for it for every man whose death was prevented within a decade after having had a PSA test.
Dr. Peter B. Bach, a physician and epidemiologist at Memorial Sloan-Kettering Cancer Center, says one way to think of the data is to suppose he has a PSA test today. It leads to a biopsy that reveals he has prostate cancer, and he is treated for it. There is a one in 50 chance that, in 2019 or later, he will be spared death from a cancer that would otherwise have killed him. And there is a 49 in 50 chance that he will have been treated unnecessarily for a cancer that was never a threat to his life.
Prostate cancer treatment can result in impotence and incontinence when surgery is used to destroy the prostate, and, at times, painful defecation or chronic diarrhea when the treatment is radiation.
As soon as the PSA test was introduced in 1987, it became a routine part of preventive health care for many men age 40 and older. Experts debated its value, but their views were largely based on less compelling data that often involved statistical modeling and inferences. Now, with the new data, cancer experts said men should carefully consider the possible risks and benefits of treatment before deciding to be screened. Some may decide not to be screened at all.
For years, the cancer society has urged men to be informed before deciding to have a PSA test. “Now we actually have something to inform them with,” Dr. Brawley said. “We’ve got numbers.”
The publication of data from the two new studies should change the discussion, said Dr. David F. Ransohoff, an internist and cancer epidemiologist at the University of North Carolina. “This is not relying on modeling anymore,” he said. “This is not some abstract, pointy-headed exercise. This is the real world, and this is real data.”
Dr. H. Gilbert Welch, a professor of medicine at Dartmouth who studies cancer screening, also welcomed the new data. “We’ve been waiting years for this,” he said. “It’s a shame we didn’t have it 20 years ago.”
Both reports were published online Wednesday by The New England Journal of Medicine. One involved 182,000 men in seven European countries; the other, by the National Cancer Institute, involved nearly 77,000 men at 10 medical centers in the United States.
In both, participants were randomly assigned to be screened — or not — with the PSA test, whose initials stand for prostate-specific antigen. In each study, the two groups were followed for more than a decade while researchers counted deaths from prostate cancer, asking whether screening made a difference.
The European data involved a consortium of studies with different designs. Taken together, the studies found that screening was associated with a 20 percent relative reduction in the prostate cancer death rate. But the number of lives saved was small — seven fewer prostate cancer deaths for every 10,000 men screened and followed for nine years.
The American study, led by Dr. Gerald L. Andriole of Washington University, had a single design. It found no reduction in deaths from prostate cancer after most of the men had been followed for 10 years. Every man has been followed for at least seven years, said Dr. Barnett Kramer, a study co-author at the National Institutes of Health. By seven years, the death rate was 13 percent lower for the unscreened group.
The European study saw no benefit of screening in the first seven years of follow-up.
Screening is not only an issue in prostate cancer. If the European study is correct, mammography has about the same benefit as the PSA test, said Dr. Michael B. Barry, a prostate cancer researcher at Massachusetts General Hospital who wrote an editorial accompanying the papers. But prostate cancers often are less dangerous than breast cancers, so screening and subsequent therapy can result in more harm. With mammography, about 10 women receive a diagnosis and needless treatment for breast cancer to prevent one death. With both cancers, researchers say they badly need a way to distinguish tumors that would be deadly without treatment from those that would not.
When the American and European studies began, in the early 1990s, PSA testing was well under way in the United States, and many expected that the screening test would make the prostate cancer death rate plummet by 50 percent or more. Dr. Brawley was at the cancer institute then, though not directly involved with its prostate cancer screening study. But he saw the reactions.
Some urologists said the study was unethical, because some people would not be screened, and demanded it be shut down, he said. One group of black urologists encouraged black men not to participate because blacks have a greater risk of prostate cancer and it seemed obvious they should be screened.
Some thought that they would see fewer cancer deaths among screened men as quickly as five years. But it became clear that screening would not have a large, immediate effect — if it did, the studies would have been stopped and victory declared. Cancer researchers began turning to less rigorous sources of data, with some arguing that screening was preventing cancer deaths and others arguing it was not.
In the United States, many men and their doctors have made up their minds — most men over age 50 have already been screened, and each year more than 180,000 receive a diagnosis of prostate cancer. In Europe, said Dr. Fritz H. Schröder of Erasmus University, the lead author of the European study, most men are not screened. “The mentality of Europeans is different,” he said, and screening is not so highly promoted.
Both studies will continue to follow the men. It remains possible that the United States study will eventually find that screening can reduce the prostate cancer death rate, researchers say, or that both studies will conclude that there is no real reduction.
“I certainly think there’s information here that’s food for thought,” Dr. Brawley said.
The benefits of prostate cancer screening, he said, are “modest at best and with a greater downside than any other cancer we screen for.”
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