Saturday, February 25, 2012

Is it in the genes? - National Post

Louise Levy attends regular Tai-chi classes, retired three years ago from her secretarial job and says she would still be driving today if her car had not "conked out before I did." None of which would be particularly unusual, except Mrs. Levy is 101 years old.

"My mind is still clear and I don't have a memory problem," says the resident of Rye, N.Y., about the latest chapter in a life that began when movies were silent and the Model-T Ford cutting edge. "It's been absolutely marvelous."

Mrs. Levy's long and generally healthy life is the focus of a fascinating scientific study, itself at the forefront of a little-noticed but radical approach to medical research. Turning upside down the traditional quest to understand and cure specific diseases, some researchers are examining instead healthy and long-lived humans and animals for their biological secrets.

By reverse engineering the source of that vigour, scientists hope to develop drugs or supplements that could give less genetically fortunate people more protection against the ravages of aging and chronic illness.

Those researchers struggle now for recognition in a medical establishment hived off into separate wars against individual diseases. A Canadian academic, however, is calling for a tectonic shift toward what he calls "positive biology." Solving the molecular mysteries of the healthy to stave off disease and aging would make the system "much more efficient," argues Professor Colin Farrelly of Queen's University in a recent paper in the journal of the European Molecular Biology Organization.

"We think it will be more important for public health than the introduction of antibiotics," echoed Jay Olshansky, a publichealth professor at the University of Illinois who has promoted a similar concept for several years. "This will be the medical breakthrough of the 21st century when it happens.- It's going to be huge."

Continuing to just combat specific diseases, on the other hand, will produce surprisingly modest advances, he contends. While curbing infant mortality and other achievements stretched life spans by 30 years in the 20th century, even a complete cure of all cancers would increase longevity by an average of just more than three years, Prof. Olshansky has estimated.

The argument seems to be slowly gaining some traction, with Canada's federal medicalresearch agency saying it is looking seriously at positive biology.

The study that has Mrs. Levy under a microscope is identifying genes linked to long life. Gabrielle Boulianne, a Toronto biologist, and others are unscrambling similar biological puzzles in exceptional specimens of fruit flies, worms and other lower life forms. Canadian infectious-disease experts have studied the lucky few people who seem naturally resistant to HIV infection; and a U.S. clinic is probing the DNA of diabetes patients who stay remarkably free of the disease's dire complications for decades.

At the core of positive biology is not an attempt to simply identify lifestyle choices - like quitting cigarettes or French fries - that can stave off disease, though those have proven value. The goal instead is to identify the mechanisms by which some people naturally live long and well, then translate that knowledge into pharmaceutical treatments.

The centenarian study at New York's Albert Einstein College of Medicine has enrolled more than 500 men and women who have lived in good health to 100 or close to it, focusing exclusively on Ashkenazi Jews, not because of any special aging quality, but to avoid ethnic variations that might complicate results. The Einstein researchers have come up with some intriguing findings.

Rather than all being paragons of lifestyle virtue, half the centenarians were overweight or obese, 60% smoked for over 30 years - and one had a tobacco habit that stretched across nine decades, noted Dr. Nir Barzilai, who heads the project.

"It's all genetics," he said. "To be 100 years old, it's strongly genetic."

More …

Friday, February 24, 2012

'Cinderella cancers' that doctors miss: Multiple visits to the GP needed for proper diagnosis | Mail Online

Many patients with less common cancers are referred to a specialist for diagnosis only after three or more trips to their family doctor, a study has found.

Those with multiple myeloma, pancreatic, stomach and ovarian cancer – which each have fewer than 10,000 victims a year – are most likely to need several GP visits before a hospital referral.

These are the so-called 'Cinderella cancers', regarded as the poor relation in cancer diagnosis and treatment.

Around half of patients diagnosed with multiple myeloma, a blood cancer, needed three or more GP consultations first. Patients with the disease are 18 times more likely to make repeat visits compared with those with breast cancer.

But even for one in three with common cancers such as lung and colon – currently the focus of a government awareness campaign – it took three GP appointments to get to hospital.

Women, young people and older patients from ethnic minorities were most likely to have to go back to the GP most often before they were given a hospital appointment.

Researchers at Cambridge University found three-quarters of cancer patients who first went to their family doctor with suspicious symptoms were referred to hospital after only one or two consultations.

But the study, published in The Lancet Oncology journal, said there were 'wide variations' depending on the type of cancer and patient.

The most pre-referral consultations occurred when the cancer was one of the less common types, or when the patient was female, aged 16 to 24 years, or an older person from an ethnic minority.

The study, which looked at 24 different cancers, comes amid concerns that some patients are not given the best chance of beating the disease because of delays in diagnosis.

The study shows patients with breast, melanoma, testicular and endometrial cancers were more likely to be referred to a specialist after just one or two consultations.

However, those with some less common cancers such as multiple myeloma, pancreatic, stomach and ovarian, as well as those with lung and colon cancers and lymphomas, were more likely to require three or more GP visits.

The findings come from data on 41,000 patients taking part in the English National Cancer Patient Experience Survey 2010.

Dr Georgios Lyratzopoulos, clinical senior research associate at the University of Cambridge, said they showed the difficulty of detecting cancer when some 'suspicious' symptoms were found in many benign conditions.

For example, it might seem obvious that a smoker with a cough could have lung cancer, but such patients would also frequently suffer respiratory infections that have similar signs.

Joy Felgate, chief executive of the Childhood Eye Cancer Trust, said: 'This is sadly something our members have experienced all too often.

'It is time GPs sat up and took notice. Just because it's rare doesn't mean it isn't there.'

A Health Department spokesman said: 'We have committed £450million to help diagnose cancer earlier.'

Managed Care Keeps the Frail Out of Nursing Homes -

Faced with soaring health care costs and shrinking Medicare and Medicaid financing, nursing home operators are closing some facilities and embracing an emerging model of care that allows many elderly patients to remain in their homes and still receive the medical and social services available in institutions.

The rapid expansion of this new type of care comes at a time when health care experts argue that for many aged patients, the nursing home model is no longer financially viable or medically justified.

In the newer model, a team of doctors, social workers, physical and occupational therapists and other specialists provides managed care for individual patients at home, at adult day-care centers and in visits to specialists. Studies suggest that it can be less expensive than traditional nursing homes while providing better medical outcomes.

The number of such programs has expanded rapidly, growing from 42 programs in 22 states in 2007 to 84 in 29 states today. In New York City, a program run by a division of CenterLight Health System, formerly known as the Beth Abraham Family of Health Services, has over 2,500 participants at 12 sites in the metropolitan area.

"It used to be that if you needed some kind of long-term care, the only way you could get that service was in a nursing home, with 24-hour nursing care," said Jason A. Helgerson, the Medicaid director for New York State. "That meant we were institutionalizing service for people, many of whom didn't need 24-hour nursing care. If a person can get a service like home health care or Meals on Wheels, they can stay in an apartment and thrive in that environment, and it's a lower cost to taxpayers."

The recent influx of adult day-care centers and other managed care plans for the frail elderly is being driven by financial constraints as President Obama and Congressional leaders seek hundreds of billions of dollars in savings in Medicare and Medicaid. Nursing homes, which tend to rely heavily on Medicare and Medicaid dollars, are facing enormous financial pressure — Mr. Obama's proposed budget includes a $56 billion Medicare cut over 10 years achieved by restricting payments to nursing homes and other long-term care providers.

Nationally, the number of nursing homes has declined by nearly 350 in the past six years, according to the American Health Care Association. In New York, the number of nursing homes declined to 634 this January from 649 in October 2007, and the number of beds to 116,514 from 119,691.

Over the next three years, New York State plans to shift 70,000 to 80,000 people who need more than 120 days of Medicaid-reimbursed long-term care services and are not in nursing homes into managed care models, Mr. Helgerson said.

The move away from nursing homes was highlighted on Thursday when Cardinal Timothy M. Dolan announced that the Archdiocese of New York, one of the state's largest providers of nursing home care, is selling two of its seven nursing homes and opening or planning to open seven new adult day-care centers over the next three years.

"Seniors and others who have chronic health needs should not have to give up their homes and independence just to get the medical care and other attention they need to live safely and comfortably," Cardinal Dolan said in a statement before he opened a 250-patient program at Saint Vincent de Paul Catholic Healthcare Center in the South Bronx.

These new adult day-care centers, known around the nation by the acronym PACE — Program of All-Inclusive Care for the Elderly — provide almost all the services a nursing home might, including periodic examinations by doctors and nurses, daytime social activities like sing-alongs and lectures, physical and occupational therapy and two or three daily meals. All the participants are considered eligible for nursing homes because they cannot perform two or more essential activities on their own like bathing, dressing and going to the toilet. But they get to sleep in their own beds at night, often with a home health care aide or relative nearby.

The nonprofit groups that operate them receive a fixed monthly fee for each participant and manage their entire care, including visits to specialists, hospitalizations, home care and even placement in a nursing home. Because Medicare and Medicaid pay set fees instead of paying for specific procedures, center operators are motivated to provide preventive care to avoid costly hospitalizations or nursing home care.

Some elderly people, however, spurn PACE programs because under managed care, they would have to switch their physicians to those at the PACE center or in its network.

Most elderly people want to live out their lives at home, a desire evident in interviews in the PACE center the archdiocese opened in 2009 in Harlem, which has a staff of three doctors and is visited regularly by a dentist, a podiatrist and a psychiatrist.

Edna Blandon, 74, a diabetic weakened on her left side by a stroke who relies on a wheelchair, is transported by specialized van to the Harlem PACE center three days a week and appreciates that it provides not only a home care attendant but sends a nurse every two weeks to change pills in her pillbox and load a 14-day supply of insulin into syringes that she will inject.

"My spirits would drop if I went to a nursing home," she said. "I love the fact that I can go home at night. There's no place like home. I can sit down, look at the TV and go to bed when I want."

James Harper, 70, a retired bank employee who spent 10 months at the archdiocese's Kateri Residence, a nursing home on the Upper West Side, after a stroke paralyzed his right side, enjoys yoga breathing classes and discussions about black history. Yet he gets to spend nights and weekends with his wife, Albertene, and daughter, Traci, both of whom work during the day and are not around to care for him.

"This way I'm around people," he said.

Dr. Fredrick T. Sherman, the Harlem PACE medical director, said that a 2009 study showed that PACE programs reduce lengths of stays in hospitals and delay assignments to nursing homes.

The archdiocese, whose new centers will serve a total of 1,500 people, receives an average of $4,000 a month from Medicaid for each participant and $3,300 from Medicare. By comparison, said Scott LaRue, the chief executive of ArchCare, the archdiocesan health care network, a month of nursing home care can cost the government $9,000.

Ultimately, the archdiocese hopes that half of its elderly clients will be served in community settings rather than in nursing homes, which currently serve about 90 percent of the archdiocese's clients. For-profit companies have not yet moved into the managed care market, in part because of uncertainties about reimbursement formulas and the risks of taking on a nursing home population.

The PACE population tends to be younger than that at nursing homes, which raises the question of whether many PACE clients would really need nursing homes without PACE. Dr. Sherman replies to such skepticism by saying that his clients "need that level of service — the question is where they're going to get it."

Without PACE, he said, "they're going to end up in nursing homes."

Facing a shortage of cadavers, professor turns to poetry to students anatomy | News | National Post

With dissection-ready cadavers in short supply and class sizes burgeoning, an Ottawa professor has come up with an unusual tool to teach the complexities of human anatomy: limericks.

Jacqueline Carnegie had students create the funny rhymes that incorporated anatomical concepts as part of her courses at the University of Ottawa, and suggests in a new study that writing body-part rhymes may have actually improved the amateur poets' class performance.

Her idea adds to a cluster of creative study aids — including a Korean professor's humorous comic strips and even folk songs — developed recently to make the age-old scientific discipline easier to grasp. Limericks are a variation on mnemonics: groups of words, numbers or letters that help people remember complicated terms.

But they also have a narrative component that can instill broader knowledge of the facts, Ms. Carnegie said.

"There's a phrase [students learn] that goes ' Never let monkeys eat bananas.' The first letter matches up with the first letter of the five different types of red blood cells," she said. "But it's not telling them anything about them. With a limerick you have to come up with a bit of a story."

Ms. Carnegie said she now wants to gather the best of her students' poems — including one about the gallbladder's green and yellow bile — and print a booklet that students could use.

Anatomy, the study of the bodily structure, has long been a staple of medical training and other healthsciences education. While the subject once took up more than 800 hours of class and lab time for medical students, though, the volume of teaching even for trainee doctors has fallen dramatically in recent decades, according to a 2009 U.S. study.

The reasons include increased enrolment, more subjects to teach in the curriculum and less emphasis on basic science, Ms. Carnegie notes in her paper in the journal Anatomic Sciences Education.

Human cadavers are also harder to obtain, and in higher demand for practising a variety of surgical and other procedures, as well as learning the body parts. While medical students still have at least some time dissecting real human corpses, students in other undergraduate programs can no longer observe anatomical facts in the flesh, Ms. Carnegie said.

With its odd-sounding vocabulary and complex systems, the topic has long been recognized as demanding. Somerset Maugham quotes a fictional anatomy teacher in his classic, 1915 novel Of Human
Bondage as saying students would learn "many tedious things … which you will forget the moment you have passed your final examination." One instructor at South Korea's Ajou University School of Medicine has created scores of comic strips that wittily — and sometimes with a little sexual innuendo — explain anatomical concepts.
"It's tough because it's got a language of its own," Ms. Carnegie said. "A lot of those names are long and complicated, a lot of them are derived from Latin."

The five-line limerick is wellsuited for retaining such facts because it places new information in a familiar context, uses rhyming to trigger recall and takes advantage of rhythm to promote long-term memory, she said. She had a total of just under 600 students over two years form into groups and come up with limericks, then assess each others' poems for their educational value, literary skill and anatomical accuracy.

Average course marks for the minority of students who did none of the limerick work were significantly lower than those who did all the limerick-related tasks. Although it's possible the students who did all the work are those who would have excelled anyway, Ms. Carnegie said she is convinced limericks helped the students better remember concepts.

That fits well with a modern educational approach that focuses less on rote, passive teaching of anatomy, and more on active learning by teams of students, said Dr. Wojciech Pawlina, anatomy-department chair at the Mayo Clinic college of medicine in Minnesota.

"You're not at a table trying to memorize those strange names; you're making something fun," he said. "I don't have anything against having fun in anatomy."

Thursday, February 23, 2012

Monitoring Your Health With Mobile Devices -

Dr. Eric Topol is only half joking when he says the smartphone is the future of medicine — because most of his patients already seem "surgically connected" to one.

But he says in all seriousness that the smartphone will be a sensor that will help people take better control of their health by tracking it with increasing precision. His book, "The Creative Destruction of Medicine," lays out his vision for how people will start running common medical tests, skipping office visits and sharing their data with people other than their physicians.

Dr. Topol, a cardiologist and director of Scripps Translational Science Institute in La Jolla, Calif., is already seeing signs of this as companies find ways to hook medical devices to the computing power of smartphones. Devices to measure blood pressure, monitor blood sugar, hear heartbeats and chart heart activity are already in the hands of patients. More are coming.

He acknowledges that some doctors are skeptical of these devices. "Of course, the medical profession doesn't like D.I.Y. anything," he said. "There are some really progressive digital doctors who are recognizing the opportunities here for better care and prevention, but most are resistant to change."

Dr. Topol may be right about the caution in the industry, but he is far from the only person with this vision. Apple was promoting the iPhone as a platform for medical devices in 2009. An entire marketplace is evolving that marries the can-do attitude of hacking devices with the fervor of the wellness movement.

Smartphones make taking care of yourself more of a game, Dr. Topol said. "I recommend these devices because it makes it more fun and I get more readings than if I ask them to do it manually."

The enthusiasm for this vision of do-it-yourself medicine with a smartphone, though, must be balanced with the cold reality that all of the experimenters should consult with their physicians.

Some of the attempts to turn the iPhone into a medical device are little more than toys. The 99-cent iStethoscope Pro app warns, "This app is intended to be used for entertainment purposes." Those who have bought it have given it uniformly poor reviews.

The equally poorly reviewed iStethoscope Expert 2012, also 99 cents, offers a $24 bell to enhance the sound.

I experimented with a homemade otoscope, the device doctors use to look into the ears, connected to a smartphone so I could take pictures of a family member's eardrums. My son has had infections in his Eustachian tube and the doctor likes to take a look. I figured that if I could take a picture or a video of the eardrum, I could save the trouble of him missing school to visit the doctor.

With the help of a little duct tape, I attached the phone to a small home otoscope from a company called Dr. Mom Otoscopes. It is just a lens, a light source and a plastic sleeve and sells for $27. To improve the image, I inserted a $20 close-up lens I had bought from

The biggest problem was in the software of the smartphone. The Apple camera app balanced the light and dark over the entire image, washing out the center so the eardrum was just a sea of white. The Android camera app offered the option of using spot metering so the light balance was better.

Despite all this fiddling with the optics and the software, the result was never very good. Better results require more than duct tape.

Firefly Global in Belmont, Mass., makes a medical camera and sells it directly to doctors who want to share the images with patients and save them for the future. Its line includes cameras for dentists, dermatologists and ophthalmologists. Unfortunately, the $180 to $350 cameras connect to a computer, not a smartphone.

The most prevalent diseases and the biggest markets are getting the tools first. Devices to monitor heart disease are already available.

A French start-up, Withings, has created a blood pressure cuff for $129 that connects to an iPad or an iPhone. The cuff will automatically inflate, deflate and then record the pulse rate and the blood pressure. The app will graph the pressure over time, making trends easier to see.

Withings also includes a connection to its Web site so users can share their data with their doctors either directly through their password-protected pages or through third-party sites like

The growing incidence of diabetes is by many estimates the biggest public health challenge today, so companies are developing tools to help people with the disease manage their blood sugar.

Tom Xu, the founder of SkyHealth in El Cerrito, Calif., created the Web site to help people keep track of the sugar in their blood. The numbers must be entered manually. The site works with an app for the iPhone to gather the blood glucose level and some information about when it was taken. "Our main goal of glucosebuddy is not to just record numbers. That's the boring part," he said. "Once you know how your diet affects your blood sugar, you take your health more seriously."

Other companies are beginning to integrate the hardware and software. AgaMatrix, a company that makes a blood glucose monitor, iBGStar, that attaches to the iPhone, worked with Sanofi, the pharmaceutical giant, to develop the tool. In December, the Food and Drug Administration approved the device for sale in the United States.

"When patients are dealing with chronic conditions, you might see a doctor every six weeks or two months," said Joseph Flaherty, the senior vice president for marketing at AgaMatrix. "For people to have real command over these diseases, we need to close the feedback loop and give people the information they need to make smarter decisions in real time."

Its tool, like many other pocket meters, measures the amount of glucose in the blood, but it also transfers the data to the smartphone, which helps patients to track their glucose levels over time. It is not much different from a piece of paper and a pen, but it is faster and cleaner, and it is easy to share these values with doctors and friends.

Johnson & Johnson has also spoken publicly about developing a similar device. The ultimate goal is replicating the full-body diagnostic "tricorder" from the "Star Trek" TV show, a goal that is being encouraged by a $10 million prize put up by Qualcomm, the smartphone chip maker, through the X-Prize Foundation.

Apps that simulate the lights and sound of the TV show prop are available from app stores.

Women's Chronic Pain Misdiagnosed, Undertreated, Dismissed - ABC News Radio

Women make up the vast majority of the nation's 116 million chronic pain sufferers, yet doctors frequently dismiss their complaints as all in their heads, sending them on years-long searches for relief, a patient told

Although studies have observed women's chronic pain is more frequent, more severe and longer lasting than men's, many women still are told "their problem isn't real. Your pain doesn't exist, you must be imagining this," Christin Veasley testified.

In her case, she said, back and neck pain from an old car accident became "an unwanted companion for 21 years." Since 2008, migraine headaches, facial pain and jaw pain piled on more misery, she said.

"From the moment I open my eyes each morning, the first thing I feel is pain," said Veasley, executive director of the non-profit National Vulvodynia Association, which aims to help the one in four American women and "countless adolescents" suffering invisible but excruciating genital pain at some point during their lives.

Veasley, who has recovered from vulvodynia she had in her 20s, testified on behalf of the Chronic Pain Research Alliance. She said she hopes Congress will lead the way in enacting "long overdue change to help us regain our quality of life and ability to contribute to society."

She was among five witnesses appearing at a Capitol Hill hearing on "Pain in America: Exploring Challenges to Relief," called by Sen. Tom Harkin, D-Iowa, chairman of the Senate Committee on Health, Education, Labor and Pensions.

The hearing followed publication last year of an Institute of Medicine report that included recommendations for improving diagnosis, treatment and research into chronic pain, as well as boosting health professionals' recognition of both the problem and its toll.

The cost of chronic pain exceeds $600 billion each year -- more than cancer, heart disease and diabetes combined, the IOM report found. Chronic pain is defined as pain that lasts several months or more, according to testimony from Dr. Lawrence A. Tabak, principal deputy director of the National Institutes of Health. It may crop up as persistent pain after an injury heals, or arise as a debilitating symptom of long-term diseases like arthritis, diabetes or cancer.

Often, Tabak said, people suffer from chronic pain associated with more invisible conditions like fibromyalgia, irritable bowel syndrome, chronic headaches or jaw pain -- all more common in women than men.

"The majority of my patients are women," said Dr. Timothy A. Collins, a neurologist with the Duke Pain and Palliative Care Clinic in Durham, N.C., who was not involved in the hearing.

He said migraine headache is "three times as common in women compared to men." Fibromyalgia "appears more common in women than men," and "a number of pain conditions are directly caused by abuse (sexual and physical) and unfortunately, women are more commonly on the abused side of the equation."

Collins said U.S. culture encourages women "to voice feelings, emotions and physical complaints" while generally discouraging such complaints in men.

"This tends to affect the perception of the care provider -- if there are significant emotional issues, the other complaints may become attributed to the emotional complaints," he said.

In other words, if a woman with chronic pain also suffers from depression, a doctor may attribute all of her complaints "to being depressed, so no further evaluation or treatment is needed," Collins said.

Women with chronic pain also are subject to some of the same gender discrimination that contributes to their under-treatment for cardiac disease and or arthritis. For example, a 1999 study published in the New England Journal of Medicine found that white women (and black men) were 40 percent less likely to be referred for potentially life-saving cardiac surgery.

A 2008 study published by the Canadian Medical Association found doctors were more likely to recommend knee replacement surgery to male patients with knee arthritis than to female patients, suggesting that gender discrimination might contribute to women being three times less likely to undergo knee replacement than men.

In addition, when it comes to doctors' decisions about managing pain, a February 2003 study of doctors' pain management knowledge and attitudes, published in The Journal of Pain, found that women were less likely than men to receive "optimal treatment" for post-surgical or cancer-related pain. That study also found doctors set lesser goals for chronic pain relief than for acute pain and cancer pain.

U.S. advisers back experimental obesity pill- Reuters

Experimental obesity drug Qnexa won the backing of U.S. health advisors on Wednesday, raising hopes for approval of the first prescription weight-loss pill in 13 years.

Vivus Inc's Qnexa was one of three promising obesity drugs rejected by the U.S. Food and Drug Administration in the past two years over safety concerns.

It is the first to come back up for review after more extensive clinical trials, as public health officials urge the FDA to consider a medical treatment for a condition that affects about one-third of Americans.

A panel of outside experts to the FDA voted 20-2 to recommend approval of Qnexa, saying they were convinced that the benefits it offers in treating obesity outweighed the potential heart risks and birth defects associated with the drug.

Vivus shares nearly doubled in value to $21.01 in afterhours trade following the panel vote.

Panelists did say Vivus should conduct a study on possible heart problems and supported the company's plan to limit its use to women who are not pregnant.

During discussions, panelists seemed divided on whether the heart-focused safety study should happen before or after the drug is approved. They took no formal vote on that issue. A pre-approval study could delay the time before Qnexa is available to patients.

Shares of fellow obesity drugmakers Orexigen Therapeutics and Arena Pharmaceuticals got a 17 percent boost in extended trading.

"The vote reflects the clinical community's concern about the challenge of obesity," said JMP Securities analyst Charles Duncan.

"I continue to believe Orexigen's Contrave and Vivus' Qnexa remain approvable drugs and are going to move forward," Duncan said. "I am less positive on Arena's Lorcaserin."

The FDA usually follows panel recommendations, although it is not required to. It will make a final decision by April 17.

"Everyone around the room knows obesity and its substantial health risks," said Dr. Susan Yanovski, an advisory panel member and director of the obesity and eating disorders program at the National Institutes of Health.

"I would say not treating obesity is not risk neutral. We have few treatments for obesity for those who don't respond to lifestyle treatments."

Obesity, a leading cause of diabetes, heart disease and other serious health problems, has reached epidemic proportions in the United States, with about a third of the population obese and more than half overweight.

The FDA has set a high approval bar for weight loss drugs because such a large portion of the general population is likely to want to take them, and has not approved a new obesity drug since 1999.

The agency has experienced previous high-profile safety scares involving diet drugs. In 1997, the infamous diet drug "fen-phen" was pulled from the market after reports of fatal heart-valve problems in some users. Another diet pill, Meridia, was pulled from the U.S. market in 2010 after being linked to heart problems.

The only prescription obesity drug currently approved for long-term use is Roche Holding AG's Xenical, which got the FDA's nod in 1999. GlaxoSmithKline markets a lower-dose, over-the-counter version called Alli. But both have their side effect issues, including liver problems and uncontrolled bowel movements, and provide only modest weight loss.

Qnexa, which combines the appetite suppressant phentermine and anti-seizure drug topiramate, helped patients lose at least 10 percent of their weight after a year of treatment, the company said.

FDA staff reviewers said patients taking the drug had more safety problems, including memory loss and higher heart rates, than those on a placebo, and some of these problems could get worse over time.

However, Vivus said the drug also reduced blood pressure, and a link between heart rates and heart health was not conclusive. Panelists called for the company to study whether a higher heart rate was tied to heart health.

"They need to step up to the plate and do the cardiovascular outcomes trial, and do it fast," said panel member Dr. Sanjay Kaul, professor in the division of cardiology at Cedars Sinai Medical Center in Los Angeles. "I also encourage the FDA to hold their feet to the fire."

FDA staff also noted that exposure to one of the ingredients in Qnexa has been linked to a higher rate of birth defects. A Vivus study showed topiramate caused a higher rate of oral clefts in infants of women taking the drug during pregnancy

The FDA has said the rate of potential birth defects is about two to five times higher with topiramate than with a placebo.

Vivus officials said obesity, and its common symptom diabetes, come with their own risks to pregnancy, such as stillbirth, premature birth and other complications.

Arena and Orexigen have been pitching their own fat-fighters to the FDA after rejections.

In February, Orexigen agreed with the FDA on the design of a 10,000-patient heart-safety trial required for the approval of its Contrave drug. The FDA rejected the drug pending the outcome of the trial, despite a 13-7 positive vote from a panel of FDA advisers.

The FDA is also set to review Arena's lorcaserin by June 27, after rejecting it in October 2010 because of a potential cancer risk.

Wednesday, February 22, 2012

Colonoscopy Prevents Death, a Study Affirms -

A new study provides what independent researchers call the best evidence yet that colonoscopy — perhaps the most unloved cancer screening test — prevents deaths. Although many people have assumed that colonoscopy must save lives because it is so often recommended, strong evidence has been lacking until now.

In patients tracked for as long as 20 years, the death rate from colorectal cancer was cut by 53 percent in those who had the test and whose doctors removed precancerous growths, known as adenomatous polyps, researchers reported on Wednesday in The New England Journal of Medicine. The test examines the inside of the intestine with a camera-tipped tube.

"For any cancer screening test, reduction of cancer-related mortality is the holy grail," said Dr. Gina Vaccaro, a gastrointestinal oncologist at the Knight Cancer Institute at Oregon Health and Science University who was not involved in the research. "This study does show that mortality is reduced if polyps are removed, and 53 percent is a very robust reduction."

Colorectal tumors are a major cause of cancer death in the United States and one of the few cancers that that can be prevented with screening. This year, more than 143,000 new cases and 51,000 deaths are expected. Incidence and death rates have been declining for about 20 years, probably because of increased use of screening tests and better treatments. But only about 6 in 10 adults are up to date on getting screened for colorectal cancer, according to federal estimates.

Cancer screening tests have come in for greater scrutiny recently. A government panel recommended in October that men no longer get the P.S.A. blood screening test for prostate cancer after concluding it did not save lives. The new study on colonoscopy has limitations — it is not a randomized clinical trial — but some experts say it nonetheless was well done and helps answer questions about the effectiveness of the procedure.

Earlier research had proved that removing precancerous polyps could greatly reduce the incidence of colorectal cancer. But a major question remained: Did removing the polyps really save lives? In theory, it was possible that doctors were finding growths that would not have killed the patient, or missing ones that could be fatal.

"This study puts that argument to rest," said Dr. David A. Rothenberger, a professor and deputy chairman of surgery at the University of Minnesota Masonic Cancer Center. He was not part of the study.

Robert A. Smith, the senior director for cancer control at the American Cancer Society, said, "This is a very big deal."

A team of researchers led by Dr. Sidney J. Winawer, a gastroenterologist at Memorial Sloan-Kettering Cancer Center in New York City, followed 2,602 patients who had adenomatous polyps removed during colonoscopies from 1980 to 1990. Doctors compared their death rate from colorectal cancer with that of the general population, where 25.4 deaths from the disease would have been expected in a group the same size. But among the polyp group, there were only 12 deaths from colorectal cancer, which translates into a 53 percent reduction in the death rate.

The new study did not compare colonoscopy with other ways of screening for colorectal cancer and so does not fully resolve a longstanding medical debate about which method is best. Tests other than colonoscopy look for blood in the stool or use different techniques to examine the intestine. All the tests are unpleasant, and people are often reluctant to have them.

Although doctors have differed about which method is best, they agree that it is important to get over the squeamishness and have some type of test, usually starting at age 50. Screening is worthwhile because colorectal cancer is one of the few types of cancer (cervical and skin cancer are others) in which premalignant growths have been identified and the disease can be prevented if those growths are detected and cut out. Research indicates that not every polyp turns into cancer, but that nearly every colorectal tumor starts out as an adenomatous polyp.

Even if intestinal cancer has already developed, it can still be cured if it is found early and treated.

"Not all adenomas become cancers, and not all cancers cause death," said Ann Zauber, the lead author of the study and a statistician at Sloan-Kettering. But in many cases, she said, "we have gotten those that would have had the potential to go on and cause a cancer death."

Dr. Smith, at the American Cancer Society, said the new study on colonoscopy was well done, and noted that changes in death rates can be difficult to measure because they require long-term studies like this one.

But Dr. Harold C. Sox, an emeritus professor of medicine at Dartmouth Medical School and former editor of a leading medical journal, Annals of Internal Medicine, cautioned that the new study was not the last word. He said it was not clear that the same reduction in the death rate found in the study would occur in the general population.

Nonetheless, he said, "I suspect that removing polyps does reduce colorectal cancer mortality."

The type of evidence in this study, based on looking back at patient records, is not considered as reliable as that from a randomized controlled study, in which groups of patients are picked at random to have one treatment or another and then compared over time.

Dr. Sox also said that because all of the patients in the study had adenomatous polyps, it is not certain that the findings would apply exactly to the general population, in which this type of polyp is found in about 15 percent of women and 25 percent of men.

In addition, Dr. Sox said, the people with polyps were part of a study that provided high-quality colonoscopy, so they may not have been comparable to the general population.

Other studies have found that doctors vary in their ability to find polyps, that certain types of polyps are hard to detect and that colonoscopy is better at finding polyps in the lower part of the intestine than in its upper reaches.

Other screening tests look for blood in the stool, and if it is found, the patient is advised to have a colonoscopy. Another test, sigmoidoscopy, examines only the lower part of the colon. Barium enemas with X-rays can also show some abnormal growths. But sigmoidoscopy and barium enemas are not used much anymore in the United States.

Stool tests need to be done once a year; many people do not comply. In fact, a study from Spain in the same issue of the journal as Dr. Winawer's article found that when people were offered a stool test, only 34.2 percent took it. The figure for colonoscopy was even worse: 24.6 percent.

Colonoscopy does not have to be done every year: If there are no polyps, it is recommended just once every 10 years. People with polyps are usually told to have the test every three years.

But colonoscopy is expensive, costing hundreds or thousands of dollars, depending on whether polyps are removed and on the part of the country where it is done. It also carries small risks of bleeding or perforation of the intestine. And it requires sedation as well as strong, foul-tasting laxatives to clean out the intestines so that the doctor can look for polyps.

"Any screening is better than none," Dr. Winawer said. "The best test is the one that gets done, and that gets done well."

His study was paid for by the National Cancer Institute, Memorial Sloan-Kettering Cancer Center and private foundations dedicated to colon cancer.

Tuesday, February 21, 2012

Aging of Eyes Is Blamed in Circadian Rhythm Disturbances -


The aging eye filters out blue light, affecting circadian rhythm and health in older adults.


Dr. Martin Mainster and Dr. Patricia Turner, University of Kansas School of Medicine.

For decades, scientists have looked for explanations as to why certain conditions occur with age, among them memory loss, slower reaction time, insomnia and even depression. They have scrupulously investigated such suspects as high cholesterolobesity, heart disease and an inactive lifestyle.

Now a fascinating body of research supports a largely unrecognized culprit: the aging of the eye.

The gradual yellowing of the lens and the narrowing of the pupil that occur with age disturb the body's circadian rhythm, contributing to a range of health problems, these studies suggest. As the eyes age, less and less sunlight gets through the lens to reach key cells in the retina that regulate the body's circadian rhythm, its internal clock.

"We believe the effect is huge and that it's just beginning to be recognized as a problem," said Dr. Patricia Turner, an ophthalmologist in Leawood, Kan., who with her husband, Dr. Martin Mainster, a professor of ophthalmology at the University of Kansas Medical School, has written extensively about the effects of the aging eye on health.

Circadian rhythms are the cyclical hormonal and physiological processes that rally the body in the morning to tackle the day's demands and slow it down at night, allowing the body to rest and repair. This internal clock relies on light to function properly, and studies have found that people whose circadian rhythms are out of sync, like shift workers, are at greater risk for a number of ailments, including insomnia, heart disease and cancer.

"Evolution has built this beautiful timekeeping mechanism, but the clock is not absolutely perfect and needs to be nudged every day," said Dr. David Berson, whose lab at Brown University studies how the eye communicates with the brain.

So-called photoreceptive cells in the retina absorb sunlight and transmit messages to a part of the brain called the suprachiasmatic nucleus (S.C.N.), which governs the internal clock. The S.C.N. adjusts the body to the environment by initiating the release of the hormone melatonin in the evening and cortisol in the morning.

Melatonin is thought to have many health-promoting functions, and studies have shown that people with low melatonin secretion, a marker for a dysfunctional S.C.N., have a higher incidence of many illnesses, including cancer, diabetes and heart disease.

It was not until 2002 that the eye's role in synchronizing the circadian rhythm became clear. It was always believed that the well-known rods and cones, which provide conscious vision, were the eye's only photoreceptors. But Dr. Berson's team discovered that cells in the inner retina, called retinal ganglion cells, also had photoreceptors and that these cells communicated more directly with the brain.

These vital cells, it turns out, are especially responsive to the blue part of the light spectrum. Among other implications, that discovery has raised questions about our exposure to energy-efficient light bulbs and electronic gadgets, which largely emit blue light.

But blue light also is the part of the spectrum filtered by the eye's aging lens. In a study published in The British Journal of Ophthalmology, Dr. Mainster and Dr. Turner estimated that by age 45, the photoreceptors of the average adult receive just 50 percent of the light needed to fully stimulate the circadian system. By age 55, it dips to 37 percent, and by age 75, to a mere 17 percent.

"Anything that affects the intensity of light or the wavelength can have important consequences for the synchronization of the circadian rhythm, and that can have effects on all types of physiological processes," Dr. Berson said.

Several studies, most in European countries, have shown that the effects are not just theoretical. One study, published in the journal Experimental Gerontology, compared how quickly exposure to bright light suppresses melatonin in women in their 20s versus in women in their 50s. The amount of blue light that significantly suppressed melatonin in the younger women had absolutely no effect on melatonin in the older women. "What that shows us is that the same amount of light that makes a young person sit up in the morning, feel awake, have better memory retention and be in a better mood has no effect on older people," Dr. Turner said.

Another study, published in The Journal of Biological Rhythms, found that after exposure to blue light, younger subjects had increased alertness, decreased sleepiness and improved mood, whereas older subjects felt none of these effects.

Researchers in Sweden studied patients who had cataract surgery to remove their clouded lenses and implant clear intraocular lenses. They found that the incidence of insomnia and daytime sleepiness was significantly reduced. Another study found improved reaction time after cataract surgery.

"We believe that it will eventually be shown that cataract surgery results in higher levels of melatonin, and those people will be less likely to have health problems like cancer and heart disease," Dr. Turner said.

That is why Dr. Mainster and Dr. Turner question a practice common in cataract surgery. About one-third of the intraocular lenses implanted worldwide are blue-blocking lenses, intended to reduce the risk of macular degeneration by limiting exposure to potentially damaging light.

But there is no good evidence showing that people who have cataract surgery are at greater risk of macular degeneration. And evidence of the body's need for blue light is increasing, some experts say.

"You can always wear sunglasses if you're in a brilliant environment that's uncomfortable. You can remove those sunglasses for optimal circadian function, but you can't take out the filters if they're permanently implanted in your eyes," Dr. Mainster said.

Because of these light-filtering changes, Dr. Mainster and Dr. Turner believe that with age, people should make an effort to expose themselves to bright sunlight or bright indoor lighting when they cannot get outdoors. Older adults are at particular risk, because they spend more time indoors.

"In modern society, most of the time we live in a controlled environment under artificial lights, which are 1,000 to 10,000 times dimmer than sunlight and the wrong part of the spectrum," Dr. Turner said.

In their own offices, Dr. Mainster and Dr. Turner have installed skylights and extra fluorescent lights to help offset the aging of their own eyes.

Bridging the gap between doctors and hackers to upgrade health care - The Globe and Mail

Among some computer geeks, it's the Hacker Way: A loose model for rapidly solving problems through intense, inexpensive jam sessions among software programmers and web designers, with little planning and total freedom.

Mark Zuckerberg used the term to describe how his collaborators and employees refined Facebook with thousands of small improvements and turned it from a dorm-room project into a $100-billion corporate giant.

A small group of Montreal hackers and medical professionals will launch an experiment next weekend to test the Hacker Way against one of the most intractable, hidebound systems going: Canadian health care.

These hackers won't be the rogues remembered from the 1980s for busting into secret databases, installing viruses or stealing nuclear codes in movies. Instead, about 180 web designers, software writers and other IT experts will meet about 50 doctors, nurses and researchers to try to produce simple health-care applications that could lead to bigger innovations.

Potential cutting-edge reforms could include constructing triage apps, text-messaging programs for HIV patients, or finding a tech solution for treating seniors at home instead of at a hospital.

"The problem is that people in health know what problems they face, but they don't have access to people who can create these solutions. The people with the solutions can't even get into the health-care system. Here, we're putting them in the same room," said Hacking Health organizer Jeeshan Chowdhury, an Edmonton medical student who is in Montreal on a year-long Sauvé Scholar fellowship after studying in Oxford as a Rhodes Scholar.

One surgery resident wants to build a do-it-yourself triage app that would help guide patients to their best health-care options (and, presumably, steer less-serious cases away from crowded emergency rooms.) A research co-ordinator hopes to build a text-message program that could give HIV patients text message reminders to take medication and make appointments.

"Instead of the big billion-dollar solutions that are usually associated with health-care technology, we'll brainstorm smaller problems and deliver solutions in a couple days," said Matthew Huebert, a 29-year-old software programmer in Montreal.

"We won't solve every problem. But I expect we'll have two or three concrete solutions that will make it all worth it."

Trevor Chan, a general practitioner who spends much of his time treating the elderly in Calgary's Foothills Hospital, will look to create an IT solution that might allow some of those patients to receive care at home instead of in hospital, particularly during the lonely overnight hours. A solution might create efficient homecare visits using a combination of health records, GPS and mapping software.

"You see so many instances where people could be at home if they just had a little bit more help, if they felt a little more secure," Dr. Chan said.

Everyone from the provincial premiers to front-line health-care providers agree information technology could provide huge gains in efficiency and cut down costs. However, bridging the gap between the young upstarts who create smartphone apps and the highly structured, rule-bound world of health care is not easy.

"If you go through government channels, everything is a maze. Nothing moves," Dr. Chan said. "I think this is a great experiment."

As he searched for a sponsor for his event, Mr. Chowdhury, 28, hit hurdles with government agencies and health-care companies loath to be associated with the word "hacker." For them, the word is still associated with nefarious computer renegades stealing bank records or hijacking nuclear missiles.

Finally he found Nightingale, which sells electronic medical records systems and "managed to see past the name and didn't find the idea too out of the box," Mr. Chowdhury said.

Monday, February 20, 2012

Lives Forever Linked Through Kidney Transplant Chain 124 -

Rick Ruzzamenti admits to being a tad impulsive. He traded his Catholicism for Buddhism in a revelatory flash. He married a Vietnamese woman he had only just met. And then a year ago, he decided in an instant to donate his left kidney to a stranger.

In February 2011, the desk clerk at Mr. Ruzzamenti's yoga studio told him she had recently donated a kidney to an ailing friend she had bumped into at Target. Mr. Ruzzamenti, 44, had never even donated blood, but the story so captivated him that two days later he called Riverside Community Hospital to ask how he might do the same thing.

Halfway across the country, in Joliet, Ill., Donald C. Terry Jr. needed a kidney in the worst way. Since receiving a diagnosis of diabetes-related renal disease in his mid-40s, he had endured the burning and bloating and dismal tedium of dialysis for nearly a year. With nobody in his family willing or able to give him a kidney, his doctors warned that it might take five years to crawl up the waiting list for an organ from a deceased donor.

"It was like being sentenced to prison," Mr. Terry recalled, "like I had done something wrong in my life and this was the outcome."

As a dawn chill broke over Chicago on Dec. 20, Mr. Terry received a plump pink kidney in a transplant at Loyola University Medical Center. He did not get it from Mr. Ruzzamenti, at least not directly, but the two men will forever share a connection: they were the first and last patients in the longest chain of kidney transplants ever constructed, linking 30 people who were willing to give up an organ with 30 who might have died without one.

What made the domino chain of 60 operations possible was the willingness of a Good Samaritan, Mr. Ruzzamenti, to give the initial kidney, expecting nothing in return. Its momentum was then fueled by a mix of selflessness and self-interest among donors who gave a kidney to a stranger after learning they could not donate to a loved one because of incompatible blood types or antibodies. Their loved ones, in turn, were offered compatible kidneys as part of the exchange.

Chain 124, as it was labeled by the nonprofit National Kidney Registry, required lockstep coordination over four months among 17 hospitals in 11 states. It was born of innovations in computer matching, surgical technique and organ shipping, as well as the determination of a Long Island businessman named Garet Hil, who was inspired by his own daughter's illness to supercharge the notion of "paying it forward."

Dr. Robert A. Montgomery, a pioneering transplant surgeon at Johns Hopkins Hospital, which was not involved in the chain, called it a "momentous feat" that demonstrated the potential for kidney exchanges to transform the field. "We are realizing the dream of extending the miracle of transplantation to thousands of additional patients each year," he said.

The chain began with an algorithm and an altruist. Over the months it fractured time and again, suspending the fates of those down the line until Mr. Hil could repair the breach. Eventually, he succeeded in finding needle-in-a-haystack matches for patients whose antibodies would have caused them to reject organs from most donors.

Until now, few of the donors and recipients have known one another's names. But 59 of the 60 participants consented to be identified by The New York Times and to tell the stories, each with distinct shadings, that ultimately connected them.

Despite an intensely bitter breakup, a Michigan man agreed to donate a kidney for his former girlfriend for the sake of their 2-year-old daughter. A woman from Toronto donated for her fifth cousin from Bensonhurst, Brooklyn, after meeting him by chance in Italy and then staying in touch mostly by text messages.

Children donated for parents, husbands for wives, sisters for brothers. A 26-year-old student from Texas gave a kidney for a 44-year-old uncle in California whom he rarely saw. In San Francisco, a 62-year-old survivor of Stage 4 Hodgkin's lymphoma donated for her son-in-law.

On Aug. 15, Mr. Ruzzamenti's kidney flew east on a Continental red-eye from Los Angeles to Newark and was rushed to Saint Barnabas Medical Center in Livingston, N.J. There it was stitched into the abdomen of a 66-year-old man.

The man's niece, a 34-year-old nurse, had wanted to give him her kidney, but her Type A blood clashed with his Type O. So in exchange for Mr. Ruzzamenti's gift, she agreed to have her kidney shipped to the University of Wisconsin Hospital in Madison for Brooke R. Kitzman's transplant. It was Ms. Kitzman's former boyfriend, David Madosh, who agreed to donate a kidney on her behalf despite their acrimonious split.

Mr. Madosh's kidney flew to Pittsburgh for Janna Daniels, a clerical supervisor, who got her transplant at Allegheny General Hospital. And her husband, Shaun, a mechanic, sent his kidney to Mustafa Parks, a young father of two at Sharp Memorial Hospital in San Diego.

On and on the chain extended, with kidneys flying from coast to coast, iced down in cardboard boxes equipped with GPS devices and stowed on commercial aircraft.

In a system built on trust, one leap of faith followed another. The burdens of scheduling operations all across the country — so donors would not have to travel — meant that operations were not always simultaneous, or even sequential. The most worrisome risk was that donors would renege once their loved ones received kidneys.

After John A. Clark of Sarasota, Fla., got a transplant on Sept. 28 at Tampa General Hospital, his wife, Rebecca, faced a 68-day wait before it was her turn to keep the chain going. Ms. Clark said that it crossed her mind to back out, but that she swatted away the temptation.

"I believe in karma," Ms. Clark said, "and that would have been some really bad karma. There was somebody out there who needed my kidney."

An Organ to Spare

It is considered a quirk of evolution that humans have two kidneys when they need only one to filter waste and remove excess fluid from the body. Yet when kidneys fail, whether from diabetes orhigh blood pressure or genetic disorders, they tend to fail in tandem.

Death can arrive in a matter of weeks for many renal patients if they do not have their blood cleansed through dialysis. The process takes almost four hours, three times a week, and leaves many too drained to work. Only half of dialysis patients survive more than three years.

Many of the 400,000 Americans who are tethered to dialysis dream of a transplant as their pathway back to normal. But with the demand for kidneys rising faster than the number of donors, thewaits have grown longer. While about 90,000 people are lined up for kidneys, fewer than 17,000 receive one each year, and about 4,500 die waiting, according to the United Network for Organ Sharing, which maintains the wait list for the government.

Only a third of transplanted kidneys come from living donors, but they are coveted because they typically last longer than cadaver kidneys. For kidneys transplanted in 1999, 60 percent of organs from live donors were still functioning after 10 years, compared with 43 percent of organs from deceased donors.

Although other living tissue can be transplanted — slices of pancreas, liver and intestine, bone marrow and lobes of lung — kidneys are uniquely suited because donors have a spare and the operations are almost always successful.

A reason there are not more live kidney donations, however, is that about a third of transplant candidates with a willing donor find that they are immunologically incompatible. Some, because of previous transplants, blood transfusions or pregnancies, may have developed antibodies that make them highly likely to reject a new kidney.

Using a blood-filtering technique known as plasmapheresis, doctors can now lower the odds that a recipient will reject an incompatible kidney. But the procedures are taxing and expensive.

Domino chains, which were first attempted in 2005 at Johns Hopkins, seek to increase the number of people who can be helped by living donors. In 2010, chains and other forms of paired exchanges resulted in 429 transplants. Computer models suggest that an additional 2,000 to 4,000 transplants could be achieved each year if Americans knew more about such programs and if there were a nationwide pool of all eligible donors and recipients.

Such transplants ultimately save money as well as lives. The federal Medicare program, which pays most treatment costs for chronic kidney disease, saves an estimated $500,000 to $1 million each time a patient is removed from dialysis through a live donor transplant (the operations typically cost $100,000 to $200,000). Coverage for kidney disease costs the government more than $30 billion a year, about 6 percent of the Medicare budget.

Dialysis, which in the United States is almost always administered in outpatient clinics, saps the productivity of caregivers as well as of patients. Nearly two years ago, Kent Bowen, 47, of Austin, Tex., gave up his job hanging gutters, and much of his freedom, so he could provide dialysis at home to his mother, Mary Jane Wilson.

Before donating a kidney for her as part of the chain on Dec. 7 at Methodist Hospital in Houston, Mr. Bowen said he looked forward not only to helping his mother, but also to a long-deferred fishing trip.

"In all actuality," he said, "giving a kidney is a small price to pay for getting my life back."

Understanding the Pain

Garet Hil and his wife, Jan, may never fully recover from the snowy night in February 2007 when they took their 10-year-old daughter in with flu symptoms and emerged with a shocking diagnosis of nephrophthisis, a genetic kidney-wasting disease. They could not imagine sacrificing her youth to dialysis.

Because Mr. Hil and his daughter shared the same blood type, he assumed he would be able to give her one of his kidneys. But two days before surgery, doctors canceled the operations after discovering that his daughter had developed antibodies that would most likely cause rejection.

Jan Hil and six other family members volunteered but were also ruled out. Mr. Hil and his daughter joined several of the registries that had started to arrange kidney exchanges, but the pools were small and they never found a match. Fortunately, one of Mr. Hil's nephews then was tested and was able to donate.

After the successful transplant, Mr. Hil, a veteran business executive, could not shake his frustration that a more effective registry for paired kidney donation did not exist. "The exchange systems out there weren't industrial strength," he said.

By the end of 2007, the Hils had formed the National Kidney Registry and rented office space in an old clapboard house in Babylon, N.Y. The couple invested about $300,000 to start it, and Mr. Hil, who is now 49, ran the registry without a salary.

"The goal was very simple: get everybody transplanted in under six months if you had a living donor," he said. "One of the things that drove us was the enormity of the problem. The other thing that drove us was that we understood the pain of being in that situation."

Mr. Hil turned out to be the right person to infuse the budding science of kidney exchange with an entrepreneurial spark. A former Marine reconnaissance ranger with an M.B.A. from the Wharton School, he had managed a series of data and logistics companies in Boston and New York and understood the worlds of both computing and finance.

He had made his money and could step off the career track to give the registry his time and the resources of his software-consulting firm. He had a background in quantitative math and enough drive to plow through medical texts about organ compatibility. Over time, he led a team in designing sophisticated software that evolved to build ever-longer chains.

Disney-hero handsome, with a cleft chin and thick wavy hair, Mr. Hil marketed his registry to hospitals with PowerPoints and passion. The transplant world initially regarded him as an interloper. But he has now persuaded 58 of the country's 236 kidney transplant centers, including many of the largest, to feed his database with information about pairs of transplant candidates and their incompatible donors.

Starting at 5 a.m. each workday, Mr. Hil manipulates several hundred pairs into transplant chains with a few clicks of a mouse. Last year, he arranged 175 transplants this way, including the 30 in Chain 124, more than any other registry. On average, patients received transplants about a year after being listed.

The same year that Mr. Hil's daughter got sick, Congress amended the National Organ Transplant Act to clarify that paired exchanges do not violate federal laws against selling organs. The blessing from Washington broke down resistance in many hospitals just as the National Kidney Registry was opening for business.

The Evolving Chain

Although the first live kidney was transplanted in 1954 in Boston, three decades passed before a Stony Brook University surgeon named Felix T. Rapaport first theorized about kidney swaps in a 1986 journal article. Korean surgeons completed the first exchanges in 1991, but they were not successfully attempted in the United States for nearly another decade.

Simple swaps among two pairs, with the operations performed at the same hospital on the same day, quickly evolved into complex exchanges among three pairs and then four and then six.

Then in 2007, a transplant surgeon at the University of Toledo Medical Center, Dr. Michael A. Rees, had a forehead-slapping insight. If an exchange began with a Good Samaritan who donated to a stranger, and if the operations did not have to be simultaneous, a chain could theoretically keep growing, limited only by the pool of available donors and recipients. Dr. Rees reported in 2009 that he had strung together a chain of 10 transplants.

Mr. Hil seized on the idea and set out to build an algorithm that would enable even more transplants. Nowadays, his pool typically consists of 200 to 350 donor-recipient pairs. That is enough to generate roughly a googol — 10 to the 100th power — of possible chains of up to 20 transplants if all of the pairs are compatible, said Rich Marta, the registry's senior software designer.

The program quickly eliminates matches that will not work because of incompatible blood types or antibodies, or because a transplant candidate insists that a donor be under a certain age or a close immunological match. It then assembles up to a million viable combinations at a rate of 8,000 per second.

The algorithm ranks the possible combinations by the number of transplants they would enable, with weight given to chains that find kidneys for hard-to-match patients and those who have waited a long time.

There are several registries like Mr. Hil's, each with a distinct approach. Largely unregulated by government, they invite sensitive questions about oversight and ethics, including how kidneys are allocated. A number of medical societies are convening in March to seek consensus on that and other issues related to paired exchanges.

Mr. Hil knows the patients in his pool only by code names and leaves all personal interactions to the hospitals. He keeps several chains running at a time, and says tending to them is like playing three-dimensional chess.

Chain 124 even included one pair that was immunologically compatible. Josephine Bonventre, a 40-year-old real estate agent from Toronto with Type O blood, could have donated a kidney directly to her fifth cousin, Cesare Bonventre, a 27-year-old tile worker from Brooklyn with Type B.

But a second level of matching requires the synching of six antigens, a series of proteins that determine compatibility. By joining the chain and donating down the line, on Dec. 6 at NewYork-Presbyterian Hospital, Josephine enabled Cesare to get a stronger match — three antigens instead of one. Her donation as a valued Type O then set off the final 11 transplants.

The registry did not charge transplant centers for its services until 2010, when Mr. Hil imposed fees to help cover costs. Hospitals now pay membership dues and a charge of $3,000 per transplant that is reimbursed by many private insurers but not by Medicare. The transplant recipients must be insured.

Each year, the registry's chains have grown longer, with Chain 124 topping the previous record by seven transplants. "We've just scratched the surface," said Mr. Hil, who wears gold kidney-shaped cufflinks.

Long transplant chains save more lives than short chains. But they come with trade-offs because the longer they grow, the higher the risk that a donor will renege or that a link will break for other reasons.

The record-breaking chain survived its share of logistical setbacks. On Aug. 29, after the first five transplants, Mr. Hil lost a link because a donor could not take the necessary two to four weeks away from work. Later that day, he lost another when a transplant coordinator informed him that a potential recipient was an illegal immigrant and therefore could not be covered by Medicare.

In late October, an entire segment fell apart when a donor at California Pacific Medical Center in San Francisco backed out for unexplained "personal reasons." It was as if one domino had fallen short of the next, leaving those still standing frozen in place.

"This makes us all sick," Dr. Steven Katznelson e-mailed Mr. Hil. "We did not see this coming."

"Wow," Mr. Hil wrote back. The donor "just put 23 patients at risk."

The dependency of each link on the others kept patients on edge. "Things can happen," Candice Ryan fretted a few days before her Dec. 5 transplant at Massachusetts General Hospital. "You just pray that everything goes well. I can't relax until I'm asleep and on the table."

Depending on the makeup of his registry at any moment, Mr. Hil likes to stretch his chains as long as reasonable and then end them if a donor is difficult to match or if one chain is draining others of potential transplants.

He does so by arranging for the final kidney to go to a fortunate transplant candidate like Mr. Terry who does not have a willing donor.

The Initial Link

Until recently, hospitals regularly turned away Good Samaritan donors on the working assumption that they were unstable. That has changed somewhat with experience. But when Rick Ruzzamenti showed up at Riverside Community Hospital asking to give a kidney to anyone in need, he still underwent rounds of psychological screening as well as medical tests.

The doctors and social workers did not know what to make of Mr. Ruzzamenti at first. He had a flat affect and an arid wit, and did not open up right away. As the hospital's transplant coordinator, Shannon White, pressed him about his motivations and expectations, he explained that his decision seemed rather obvious.

"People think it's so odd that I'm donating a kidney," Mr. Ruzzamenti told her. "I think it's so odd that they think it's so odd."

The hospital wanted to make sure that he was not expecting glory, or even gratitude. Mr. Ruzzamenti stressed that no one should mistake him for a saint.

He had, after all, been a heavy drinker in his youth and had caroused his way through the Navy. He could be an unsmiling presence at work, where he helped manage a family electrical contracting business. He admitted that he did not visit his parents or grandmother enough.

Despite his occasional surliness, Mr. Ruzzamenti said he felt driven to help others when possible. And as he considered the relative risks and benefits of organ donation, particularly to relieve a whole chain of suffering, it just made so much sense. "It causes a shift in the world," he said.

Perhaps, he said, there was some influence from a Tibetan meditation he had practiced when he was first drawn to Buddhism six years ago. It is known as Tonglen. "You think of the pain someone's in, and imagine you take it from them and give them back good," he said.

Mr. Ruzzamenti said he was in a position to donate only because the economy had dried up so much of his work. He was essentially unemployed and could take time off to recuperate. The 30 kidney recipients, he observed dryly, could "all thank the recession."

When Mr. Ruzzamenti told his wife, My Nhanh, about his plans, she made it abundantly clear, despite her rudimentary English, that she would leave him and return to Vietnam if he followed through. She had immigrated only eight months before, after a marriage largely arranged by the Buddhist temple where Mr. Ruzzamenti volunteered as a groundskeeper. If he died on the table, she demanded, how would she get by in a country where she felt so out of place?

"I wanted to scare him," Ms. Ruzzamenti, who is known as Lucy, said as she combed her husband's close-cropped hair with her fingers. "And to tell him that it scares me."

Mr. Ruzzamenti was impressed by his petite wife's ferocity — "She's a bully," he said — but he disregarded her threat. He knew research showed that the risk of death from kidney retrieval surgery was 3 in 10,000 and that people with one kidney live as long as those with two. To him, there was little doubt that any good he created would far outweigh any temporary discomfort to him or his wife.

As it happened, Mr. Ruzzamenti experienced an unusual level of pain during his recuperation at Riverside. It sometimes left him balled up in agony, and the Demerol only made him hallucinate. He did not really want company. But when the pain stirred him awake at night, he could see Lucy sleeping in the hospital bed beside his.

Acts of Devotion

There were other love stories along the way.

Gregory Person and Zenovia Duke, both now 38, had been junior high prom dates in 1987 in Astoria, Queens. They lost touch and then reconnected on Facebook after each had divorced. They saw each other occasionally, but he lived in Queens and she near Albany, so the relationship never got serious.

Not long after they reconnected, Mr. Person's half-sister died of kidney failure and he pledged to help someone else beat the disease if ever given the chance. Then Ms. Duke learned she needed a transplant.

On Aug. 31, Ms. Duke received a kidney from a woman in California and Mr. Person sent his to Ohio. As they recuperated at NewYork-Presbyterian , Mr. Person found himself regularly hobbling down to her room. Once they were both back on their feet, they started dating more regularly.

"I've never had any person in my life actually do what they say they're going to do," Ms. Duke said, "especially men. It spoke volumes that he was a man of his word."

It was a different kind of devotion that led David Madosh, 47, to donate a kidney for Brooke Kitzman, 30. Their four-year relationship, which had produced a 2-year-old daughter, soured just as he was getting tested as a potential donor. The breakup, caused partly by the strains of her illness, was ugly enough that when Ms. Kitzman later matched to become part of the chain, she put the odds at no better than 50-50 that Mr. Madosh would still donate.

But Mr. Madosh, who lost his mother when he was 5, did not want his daughter, Elsie, to lose hers.

The youngest of 12 children, he said he had been passed from one foster home to the next, eight in all, some that he described as little more than labor camps. "I don't want my daughter to have to experience that," said Mr. Madosh, a tree cutter by trade. "No matter what it takes, a daughter needs her mother."

Ms. Kitzman said she was grateful for Mr. Madosh's kidney, and had told him so when they visited in a hospital corridor. But both made it clear that his act of charity had barely eased the tension between them.

Mr. Madosh said he took satisfaction enough from seeing Elsie at play with her re-energized mother. "When her mama comes to get her, and she gives her hugs and kisses, that's it right there," he said.

A Wish Come True

On Dec. 19, Chain 124 hurtled toward its conclusion with a final flurry of procedures at Ronald Reagan U.C.L.A. Medical Center in Los Angeles. Between dawn and dusk, three kidneys were removed and three were transplanted in neighboring operating rooms. One flew in from San Francisco. The last took off for O'Hare.

At the end of the cluster were Keith Zimmerman, 53, a bearish, good-humored man with a billy-goat's beard, and his older sister, Sherry Gluchowski, 59. She had recently moved from California to Texas but returned to donate her kidney.

The siblings had always been close, although family members marveled at their ability to bicker for 15 minutes over the proper way to construct a peanut butter sandwich. Their mother, Elsa Rickards, remembered teaching them as children "that they might not have their mommy and daddy all the time, but they will always have each other."

Mr. Zimmerman, who runs a repossession firm with his wife in Santa Clarita, had been given a diagnosis of kidney disease 25 years ago. With the help of a nutritionist, he had managed to avoid dialysis until the very last day before his transplant, when his doctor said the procedure was needed to clear his body of excess fluid.

In his hospital room before surgery, with seven family members shoehorned into every nook, Mr. Zimmerman calmed his nerves by listening to Aaron Neville on his iPod. He said he considered himself "the lottery winner" in the chain because his kidney would be coming from a healthy 28-year-old, Conor Bidelspach of Bend, Ore.

The surgery to remove a kidney, known as a nephrectomy, is remarkably bloodless these days. With Mr. Bidelspach on the table, Dr. Peter G. Schulam cut four dime-sized incisions on the left side of the abdomen. Through tubes inserted in the openings, the surgeon and his team maneuvered their cauterizing scalpels and a laparoscopic camera, which relayed images of Mr. Bidelspach's insides to monitors overhead.

The scalpel's super-heated pincers clamped down like crab claws, searing the kidney from surrounding tissue. There was no need to cut any muscle.

Once the kidney was free of connective tissue, Dr. Schulam clamped and snipped the renal artery and vein and ureter. He captured the kidney in a plastic bag, cinched it shut, and withdrew it quickly through a finger-length incision along the pelvic line.

The doctor poured the kidney into a bowl of ice and drained it of remaining blood. The slush in the blue bowl turned fruit-punch pink.

As others stitched up Mr. Bidelspach, Dr. Schulam wheeled the kidney on a cart into an adjoining operating room, where Mr. Zimmerman was already anesthetized. After stretching a hole in Mr. Zimmerman's midsection with a metal retractor, Dr. Jeffrey L. Veale lowered the kidney into place and sewed in the renal artery and vein. As soon as he unclamped them, the kidney pinked up with blood flow. Before attaching the ureter to the bladder, he gently massaged the tip of the narrow tube between two fingers and watched it spurt a few drops of urine.

"No more dialysis for Mr. Zimmerman," Dr. Veale declared. "This total stranger's kidney is making him pee." He left Mr. Zimmerman's own kidneys to shrivel harmlessly in place (removing them would add to surgical risk).

Meanwhile, Dr. Schulam was in yet another operating room removing Ms. Gluchowski's kidney. He placed it in a plastic bag filled with a preservative solution and knotted it shut, like a goldfish brought home from the pet store. It was packed in a plastic tub, topped with ice, and loaded into a cardboard box marked "Left Kidney — Donated Human Organ/Tissue for Transplant — Keep Upright."

A courier in one of Quick International's big red vans drove Sherry Gluchowski's kidney through stop-and-go traffic on Interstate 405 to the Los Angeles airport. Cynthia Goff, an operations supervisor for the courier company who had volunteered to accompany the kidney to Chicago, rolled the box into the terminal strapped atop her carry-on with a bungee cord. A pit bull, waiting to be placed in its travel kennel, strolled by and sniffed.

After security agents checked the box with a desktop scanner, Ms. Goff rolled the kidney down the concourse, past a currency exchange and a store selling Elmo dolls for Christmas. Escorted onto United 564, an overnight flight that would land in Chicago at 5 a.m., she stowed the box in the business-class closet, next to a flight attendant's overcoat.

Airplanes carrying donor organs are granted special status, allowing them to move to the front of takeoff lines and ahead of air traffic. Mr. Hil, who tries to avoid routing kidneys on connecting flights and always schedules backups, said none of his registry's transplants had been held up by transportation problems.

By the time Ms. Gluchowski's kidney made it to Loyola and was transplanted into Mr. Terry, it had been cold for almost 12 hours. Early studies have found no evidence that shipping live kidneys such distances affects their immediate function.

Chain 124 ended at Loyola because Mr. Hil had arranged for the final kidney to go to a hospital that had produced a Good Samaritan donor to start a chain in the past, thus closing a loop. Dr. John Milner, a transplant surgeon at Loyola, said he then selected Mr. Terry to receive the kidney because he was the best immunological match on the hospital's wait list.

When Dr. Milner called with the news in early December, Mr. Terry was floored at his remarkable good fortune. Having felt unfairly condemned when he was first placed on dialysis, he now wondered what he had done to deserve a gift that 90,000 others needed just as much.

As it sank in that his would be the last of 30 interconnected transplants, Mr. Terry began to feel guilty that he would be ending the chain. "Is it going to continue?" he asked Dr. Milner. "I don't want to be the reason to stop anything."

"No, no, no," the doctor reassured him. "This chain ends, but another one begins."