FDA Okays Methylnaltrexone Bromide (Relistor) for Opioid-Induced Constipation

By Peggy Peck
26 april 2008-- The FDA has approved methylnaltrexone bromide (Relistor) injection for treatment of opioid-induced constipation, a common condition among patients on continuous medication for pain relief in late-stage illness.
Opioids interfere with normal bowel function by relaxing intestinal smooth muscle cells, which prevents the intestine from contracting normally. Methylnaltrexone bromide blocks opioid receptors on the intestinal muscle cells thus allowing the bowels to function normally.
The FDA approval was based on two randomized, double-blind placebo-controlled studies involving 287 participants and conducted over four months.
The median age of study participants was 68; 51% were women.
All patients had advanced late-stage illnesses with a life expectancy of less than six months. Participants had had either fewer than three bowel movements in the week before treatment or no bowel movement for more than two days.
The FDA said patients who were treated with methylnaltrexone bromide had a significantly higher rate of elimination than those receiving placebo.
Methlynaltrexone bromide is an injectable medication that can be administered as needed, but not more than once in a 24-hour period.
The recommended dose is 8 mg for patients weighing 38 to less than 61 kg (84 to less than 135 lb) or 12 mg for patients weighing 62 to 114 kg (136 to 251 lb). Patients whose weights fall outside those ranges should be dosed at 0.15 mg/kg.
The recommended starting schedule is one dose every other day as needed for patients with late-stage advanced illness.
The drug is not recommended for patients with known or suspected intestinal obstructions.
Common side effects included abdominal pain, gas, nausea, dizziness, and diarrhea. The safety and effectiveness of methylnaltrexone bromide have not been studied in pediatric populations.
Methlynaltrexone bromide is manufactured by Wyeth Pharmaceuticals Inc., in Philadelphia, and Progenics Pharmaceuticals in Tarrytown, N.Y.

FDA Advisers Find LASIK Safe But Oversold

By Peggy Peck
26 april 2008 -- Laser-assisted in situ keratomileusis (LASIK) is safe and well accepted, an FDA advisory panel concluded today.
Although overzealous marketing may lead to inappropriate use of LASIK, such questionable clinical decision-making does not detract from the device's overall safety, found the agency's Ophthalmic Devices Advisory Committee after a day of hearings.
Jayne Weiss, M.D., of the Kresge Eye Institute in Detroit, who chairs the panel, said that based on available information "the vast majority of patients with LASIK do very well and are very happy and see very well."
Dr. Weiss said that one common theme during public testimony that occupied most of the morning session was "aggressive marketing. The other was LASIK as a commodity. The FDA does not regulate marketing, but I agreed that it is a problem."
Another issue, she said, was patient selection. The testimony suggested that there was "inadequate informed consent and the fact that some patients were poor candidates. That comes under malpractice and that is something that the field should monitor."
She said the day's hearing was "really a referendum on the performance of LASIK by some surgeons who should be doing a better job."
Nonetheless, Dr. Weiss said it was clear from testimony that the FDA's "LASIK postmarketing assessment surveys don't adequately address the severity of adverse effects."
The panel cited three major concerns -- the possibility of cataracts, endothelial cell loss, and induced astigmatism. It recommended that these concerns be reflected in the LASIK label.
The panel said that intraoperative complications such as flap complications should be differentiated from postoperative complications in the list of adverse events that must be reported to the FDA. Moreover, adverse events should include halos and glares as well as significant loss of visual acuity.
The panel suggested labeling changes to more fully state what and how problems can occur, including extreme blurriness, haze, glare, halos, and starbursts. It also suggested that the label take note of possible depression or psychological problems.
The panel agreed that LASIK labeling should include additional information or guidance about postoperative intraocular pressure, additional guidance for implant measurement for post LASIK cataract surgery, and stronger cautionary language concerning risks in patients with a strong history of keracatonis. The panel also recommended adding language about risks associated with hormone replacement therapy or a history of depression.
The panel also recommended that the FDA's LASIK Web site should include photographic illustrations of visual disability, detailed statistics as to risk of side-effects or complications, and an expanded explanation of the benefits of LASIK, i.e. that improving distance vision will mean the need for reading glasses.
The advisory panel set aside the entire morning for public testimony, much of it dominated by patients and family members of patients who claimed that LASIK surgery left them disabled, depressed, and in some cases suicidal.
A father told the story of his son, a law student who had LASIK because he had developed dry eye as a result of contact lens use. Before LASIK, the son was successful, outgoing, with no history of mental health issues, his father said.
Before surgery, the son was told that postoperative glare and halos would be no worse than with contacts. According to the father, after surgery the son had large starbursts and halos at night, triple overlapping images, and ghosting off white objects in low light, as well as painful dry eye.
The father read a suicide letter in which his son wrote that he fell into a suicidal depression because of his eye problems.
But the panel also heard testimony from a number of patients and surgeons who praised the surgery. An Army ophthalmologist testified that members of the Army's special forces units were especially pleased with LASIK results.

ASA: Laparoscopic Surgery Gets Good Grades for Pancreatectomy

By Charles Bankhead
NEW YORK, 26 april 2008 -- For patients with cancer confined to the pancreatic body or tail, laparoscopic left pancreatectomy leads to less morbidity, lower complication rates, and shorter hospitalization, according to data reported here. Compared with an average nine days in the hospital after open surgery, laparoscopic patients were two-thirds less likely to stay for more than seven days, David A. Kooby, M.D., of Emory University in Atlanta, said at the American Surgical Association meeting."If we can offer someone a more cosmetically acceptable result, do it safely, and potentially get them out of the hospital faster -- that's not a bad thing," Dr. Kooby said in an interview.
Laparoscopic left pancreatectomy has increased in recent years, but its performance compared with open pancreatectomy has not been well studied. Dr. Kooby presented findings from an analysis of eight centers' combined experience with the laparoscopic procedure from 2002 through 2006.
The analysis included 159 patients who had laparoscopic procedures and 508 patients who had open surgery. Indications for surgery were solid lesion (307, 46%), cystic lesion (295, 44%), and pancreatitis (65, 10%). Twenty laparoscopic procedures were converted to open surgery.
Dr. Kooby said 200 patients in the open-surgery group were matched with 142 patients in the laparoscopic group by age, American Society of Anesthesiologists surgical risk category, resected pancreas length, tumor size, and diagnosis. The groups did not differ significantly in positive margins (8% versus 7% with open surgery), operative time (216 versus 230 minutes), or leakage (18% versus 11%).
Compared with open surgery, laparoscopic left pancreatectomy significantly significantly reduced:
Blood loss, 357 versus 588 cc, P<0.01
Complication rate, 40% versus 57%, P<0.01
Hospital length of stay, 5.9 versus 9.0 days, P<0.01
In multivariate analysis, laparascopic left pancreatectomy remained a significant predictor of a shorter hospital stay (OR 0.33, P<0.01).
The biggest difference in postop complications involved wound infection. Dr. Kooby said the rate of wound infection in the laparoscopic group was about a third of that in open-surgery patients.
Ordinarily, a randomized clinical trial would be warranted to compare two treatments, but Dr. Kooby said such a trial is unlikely in this case. Of the more than 30,000 patients with newly diagnosed pancreatic cancer each year, about a third go to surgery. Of those, 10% to 15% have cancer limited to the tail or body of the pancreas, but two thirds would not be candidates for laparoscopic surgery because the cancer has grown into surrounding tissues.
"You're talking about 500 or 750 cases a year," said Dr. Kooby.
"We have enough data to say that, in the right hands and with the right indications, [laparoscopic surgery] is not only an acceptable approach but it may actually be the preferred approach," said Dr. Kooby.
Dr. Kooby reported no disclosures.
Primary source: American Surgical Association MeetingSource reference:Kooby DA, et al "Multicenter analysis of 667 left pancreatectomies: should the laparoscopic approach become standard?" ASA Meeting 2008; Abstract 15.

ELCC: Immunotherapy for NSCLC Well-Tolerated

By Michael Smith
GENEVA, 26 april 2008-- An immune-boosting treatment for non-small-cell lung cancer patients with completely resected stage IB or II disease is safe and well tolerated, researchers said here. The 44-week results of a phase II study of MAGE-A3, a tumor-specific antigen, also show a nonsignificant "strong signal" in favor of better survival and longer time to relapse, according to Johan Vansteenkiste, M.D., Ph.D., of University Hospital of Louvain in Belgium, and colleagues. The improvements are tending to be similar to those seen with chemotherapy, Dr. Vansteenkiste reported at the European Lung Cancer Conference, although a phase III trial, now underway, is needed to demonstrate efficacy. "Surgical resection is the standard treatment for patients with early stage lung cancer, but after complete resection about 50% will relapse and die from their cancer," Dr. Vansteenkiste said.
He added that post-op chemo improves cure rates, but is "sometimes poorly tolerated by patients recovering from thoracic surgery. In addition, not all patients can withstand chemotherapy."
With MAGE-A3, he said, the reduction in the risk of relapse is currently not significant but is tending to be comparable to that seen with chemotherapy, but with minimal side effects -- mainly injection site reactions and fever over a 24-hour period.
Dr. Vansteenkiste said reactions are similar to those seen with prophylactic vaccines. "That's one of the important things about this approach," he said.
The study included 182 patients, randomized on a two-to-one basis to get either the MAGE-A3 recombinant protein or placebo. The patients were selected to have cancer that expressed the MAGE-A3 protein.
Injections were given over a 27-month period, with the first five given at three-week intervals, then eight given once every three months, the researchers said.
The primary endpoint of the study was disease-free interval, with safety, disease-free survival, overall survival, and assessment of humoral and cellular anti-MAGE-A3 immune response as secondary endpoints.
After a median of 44 weeks of follow-up, Dr. Vansteenkiste and colleagues said:
There were 69 recurrences and 57 deaths.
The disease-free interval hazard ratio was 0.75, with a 95% confidence interval from 0.46 to 1.23, in favor of patients getting the MAGE-A3 protein, although the difference at P=0.127, did not reach significance.
The hazard ratios for disease-free and overall survival were also not significant at 0.76 and 0.81 (also in favor of the MAGE-A3 group) with 95% confidence intervals from 0.48 to 1.21 and 0.47 to 1.40, respectively.
More than 98% of patients given the recombinant protein had an anti-MAGE-A3 IgG antibody response.
T-cell responses were measured in 51 patients and a CD4 T-cell response to MAGE-A3 was seen in 15 of 37 immunized patients (41%), and only in two of 14 patients who got placebo (14%).
Dr. Vansteenkiste said the study was not designed to achieve statistical significance in the efficacy endpoints. "It would be a miracle if, with only 200 patients, you had significance," he said.
Instead, he said, the researchers looked for a "promising signal" that would justify a larger, 2,000-patient phase III trial, which began enrolling patients last year.
The study was sponsored by GlaxoSmithKline the manufacturer of MAGE-A3. Dr. Vansteenkiste reported no conflicts. One of the co-authors is an employee of GlaxoSmithKline Biologicals.
Primary source: European Lung Cancer ConferenceSource reference:Vansteenkiste J, et al "Phase II randomized study of MAGE-A3 immunotherapy as adjuvant therapy in stage IB/II non-small cell lung cancer (NSCLC): 44-month follow-up, humoral and cellular immune response data" ELCC 2008; Abstract 1480.

When It Comes to Memory, It's All About Location


26 april 2008-- A new report finds that where protein-destroying machines reside in the brain's nerve cells may help determine how memories are formed, a finding that may play a role in future treatments for Alzheimer's and other brain diseases.
Wake Forest University School of Medicine researchers studying mice discovered that cylinder-shaped proteasomes, which help control protein levels, play different roles in controlling synapse strength depending on where they are in the nerve cells of the hippocampus, an area of the brain linked to memory.
When humans or animals learn and store information in their memory, these connections between cells become stronger or weaker, Ashok Hegde, associate professor of neurolobiology and anatomy at Wake Forest, said in a prepared statement. For example, if people learn to do something better, such as playing softball, the synapses that control hand-eye coordination will become stronger. If they learn to ignore something, such as the barking of a neighbor's dog, then the synapses that control paying attention will become weaker.
The findings were published in the current issue of Learning & Memory.
It is known that the degradation of proteins, which are made by cells to control cell functions, plays an important role in memory function. The team found that proteasomes in the dendrites -- the branched parts of a neuron that conduct electrical stimulation -- limit the connection strength between cells. Proteasomes in the nucleus, which contains the cell's genetic material, help maintain synapse strength for long periods of time.
The researchers are now trying to learn how to block proteasome activity specifically in the dendrites of mice to increase the strength of synapses and of memory. In their ongoing studies, the mice will be analyzed on how well they can learn to navigate a maze.
"If we see a memory enhancement when we block the proteasome in dendrites, we can use this strategy to treat memory loss," Hegde said.

How to Live Longer Without Really Trying

By MICHELLE SLATALLA
25 april 2008--MY neighbor Bruce has the healthiest lifestyle on the block. He eats small portions and skips dessert. He walks to work. His hobbies — coaching Little League, riding his bike and taking his dog on hikes — all involve getting wholesome, fresh air.
This behavior drives my husband, who has the least healthy lifestyle on the block, crazy. “You’re going to be so lonely living forever,” he yells at Bruce from our balcony, where we drink beer. “All the interesting people will be dead.”
“Yeah, good luck with that,” I chime in to show support for my husband (and Anchor Steam).
But secretly I’m on Bruce’s side. I wouldn’t mind living forever. Or at least long enough to blow out the candles on my 100th birthday cake.
Maybe I can. According to a new book that looks at the daily routines of clusters of centenarians who live in four geographically remote or culturally isolated “blue zones” of longevity — from Okinawa to a community of Seventh Day Adventists in Southern California — all I need to do to extend my life is follow a few of their simple secrets.
Eat less. Make family a priority. Banish stress. I figured it should be no problem to follow most of the common-sense tips that Dan Buettner outlines in “The Blue Zones: Lessons for Living Longer From the People Who’ve Lived the Longest” (National Geographic, 2008).
Of course, I was not going to be able to work a nightly glass of mugwort sake into my diet as easily as an Okinawan. Or spend the whole day hiking uphill like a Sardinian shepherd.
But maybe I could take advantage of the culturally isolated and geographically remote environment in which I live — my basement, in front of a computer — to create my own blue zone. I hoped, in fact, to find a way to obey the Power 9 — what Mr. Buettner nicknamed the rules of longevity — without ever getting up from my desk.
The first step was a cinch. Mr. Buettner recommends getting started by visiting http://www.bluezones.com/ to take a test called the Vitality Compass. Answer 35 questions, and voilà, it calculates your life expectancy.
I felt healthier already. Two minutes later, I received (sort of) good news.
“You are in the Blue Zone!” the Web site told me, adding that my biological age is 40, which is better than both my real age (46) and my Wii Fit age (49), but not nearly as young as the age I would like to look (23).
But then the results took a dark turn.
My life expectancy: 95.2.
My healthy life expectancy: 83.9.
While 12 years of decline was bad news for me, it would be even more of a blow to my children, who already have been warned that they won’t inherit my jewelry if they put me in a nursing home.
The only way to react to such dark news was to scoff at it, and dismiss the quiz as a publicity stunt to sell books.
Sadly, however, it turned out that the quiz results were based on a complex, 106-page algorithm developed by Dr. Robert Kane, a physician and a professor at the University of Minnesota School of Public Health.
“What the results tell you are a confirmation and a consolidation of what’s been known, for the most part,” for decades, Dr. Kane said in an interview. “The challenge now is to try to get people to use it to change behavior. Most of us know what we ought to do, but have a hard time doing it.”
Like me. If I followed all the personalized advice in the quiz’s final report, I could get as much as an extra 2.3 years — if I didn’t get struck by lightning or some unforeseen fatal disease. But even knowing that incentive, I suffered an immediate setback. Two suggestions — get more rigorous exercise and eat less — made me hungry.
A few Mint Milano cookies later, I returned to my desk determined to improve. I e-mailed my tennis doubles partner, Stacey (who is also studying to become a certified personal trainer), to volunteer to let her train me twice during the next week.
She wrote back, with suggested training sessions and gossip about the latest team scandals, which sidetracked me until my fingers had gotten such a rigorous typing “workout” that I was ready to move on to the next suggestion: avoid salt.
To accomplish this, I sat at my desk awhile, eating nothing, until I figured enough time had passed to allow me to check off the no-salt suggestion.
Next: eat more fruit.
A Google search for salty fruit yielded 456,000 results. I settled quickly on something delicious called Sweet-n-Salty Fruit-n-Nut Honey Lace Brittle. Was that so hard?
After printing out the recipe, I moved on to the next suggestion: drink red wine.
Here — while people who know me might find this hard to believe — I hit a roadblock. While it’s possible, sometimes even essential, to drink wine in front of my computer, I couldn’t imagine myself drinking red.
Seeking clarification, I phoned Mr. Buettner. “Do you really think some book is going to get me to give up white wine?” I asked.
“No, no, you don’t have to,” he said in a reassuring tone meant to lower my stress level (another suggestion from my final report). “When it comes to drinking any spirits, a woman should have a drink a day and maybe two, unless pregnant.”
“Any spirits?” I pressed.
“You get this extra little antioxidant bump” from the polyphenols in red wine, he explained. “But white wine is fine too. I know drinking alcohol helps because I looked at epidemiology studies of huge populations and saw that those who drink a little outlive those who don’t.”
No doubt because nothing reduces stress like a full glass of chardonnay. And I needed relaxation more than ever because Mr. Buettner had become part of the problem. “I’m feeling considerable stress,” I told him, “because, according to your quiz, I am not going to live to be 100.”
“You have to have won the genetic lottery to live that long,” he said. “Like, did your grandparents and all their siblings live to be 100?”
I considered. Perhaps all four grandparents combined reached that age. My only option was to tackle another of the Power 9.
“I am thinking of trying to be more likable, as page 259 of your book suggests,” I said. “But how does that help?”
“If you’re likable, you’re likely to have a better social network, and even get better health care at the doctor’s office because the people who take your blood pressure will do a better job,” he said.
Pray tell, how to become more likable? “Be interested, not just interesting,” he said. “Likable people tend to ask you a question about yourself instead of just talking about themselves.”
Taking his advice, I changed my Facebook status to say, “Michelle is wondering what YOU are thinking.”
This prompted a Facebook friend to write a post: “Funny you should ask. ...”
Encouraged by how youthful my newfound amiability made me feel, I sent a text message to my Twitter entourage that said, “I meant to mention earlier, you look really good today.”
No response. So I texted, “Did you change your hair or what?”
This backfired. One of my Twitter-hating teenagers texted, “Do you realize that everyone can see what you’re typing?”
In desperation, I was ready to take the final bit of Mr. Buettner’s advice (“Maybe you should minimize time spent on the Internet as a way to reduce stress”) and spend some quality offline time “surrounded by those who share your blue-zone values.”
So I made a pan of calorie-laden chicken tetrazzini and went across the street to Bruce’s house with it. There my husband and I found him poring over the score sheet from a Little League game (his team won 20-5, which had to have diminished his stress).
“That looks good,” Bruce said, pointing to the casserole.
“Try some,” I said.
He had seconds. I didn’t.

Study Details New Molecular Approach to Preventing Alzheimer's

By Ed Edelson
25 april 2008--German researchers are reporting a new approach to the possible prevention of the molecular "debris" that's associated with the development of Alzheimer's disease.
The basic idea -- to block the activity of an enzyme called beta-secretase -- is not new, said study lead author Dr. Kai Simons, a professor of cell biology at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden.
A number of laboratories, both academic and commercial, are working on methods to prevent the enzyme from slicing a protein into beta amyloid fragments that form the brain plaques found in people with the disease. All work on the same principle. "If we decrease the amount of cleavage, we could in all likelihood reduce the likelihood of the disease," Simons said.
Most experts now agree that formation of the beta amyloid plaques is directly linked to the development of Alzheimer's. The problem with most proposed methods of blocking beta-secretase, Simons said, is that they are designed to work outside of the affected brain cells.
"This process of cleaving takes place inside cells," he said. "We have constructed an inhibitor which binds outside, on the cell membrane, and goes into the cell where the cleavage occurs."
Reporting in the April 25 issue of the journal Science, Simons and his colleagues described both test-tube experiments and animal studies in which the combination of an anchoring molecule and a beta-secretase inhibitor reduced the formation of beta amyloid plaque by more than 50 percent over four hours, while the inhibitor alone was ineffective.
The success is just one small step toward a medically useful preventive therapy for Alzheimer's disease, Simons acknowledged. For one thing, the treatment was given by injection into the brains of the experimental animals (fruit flies and mice), something not likely to be done with people.
"This is proof of principle," Simons said. "The idea would be to get it into the blood in humans and then over the blood-brain barrier into the brain. There are many ways for molecules to get into the brain."
The blood-brain barrier is a network of tightly packed cells that prevents most molecules from entering the brain.
William J. Netzer, an Alzheimer's researcher at the Fisher Center for Alzheimer's Disease Research Foundation at Rockefeller University in New York City, called the new study "a profoundly interesting line of research."
"It is not implausible that one might improve the effectiveness of a drug by coaxing it to go into a region where the enzymes it blocks exist," Netzer said.
But medical use of such a product can raise questions, he said. "When you put an inhibitor into a living being, the chemical you put in can be modified in the body. Where a compound goes into a cell is a complicated issue when you put it into a human being," he added.
Dr. James Galvin, associate professor of neurology and psychiatry at Washington University in St. Louis, called the German research "a novel idea."
If the concept works, it would solve a puzzle about how to best target the enzyme, Galvin said. And it is a concept with broader medical possibilities, he said.
"You can potentially inhibit other enzymes where cleavage occurs within membranes," he said.

Wealth and Income Provide Buffer against Stroke

By Charles Bankhead
ROTTERDAM, 25 april 2008 -- Money might not buy love, but it can protect some people against stroke, investigators found.
In a study of more than 1,500 stroke patients, wealth and income independently predicted stroke risk in people ages 50 to 64 but not in older individuals, Mauricio Avendano, Ph.D., of Erasmus University Medical Center here, reported in the May issue of Stroke.
Dr. Avendano and co-author M. Maria Glymour, Ph.D., of Harvard, suggested that the association they found between affluence and stroke probably understate the impact of social disparities on stroke risk.
Several studies have suggested that lower socioeconomic status is associated with higher stroke risk in developing countries. In the United States, however, the association goes in the opposite direction, as stroke disparities across education and income appear to reverse at age 74, the authors said.
Almost 90% of strokes occur after 65, but the influence of socioeconomic status on stroke risk in that older age group had not been examined, they continued.
So Drs. Avendano and Glymour analyzed data from the Health and Retirement Study, a longitudinal survey of a national sample of U.S. adults 50 and older. They included 19,965 participants who were stroke-free at baseline.
Baseline assessments of wealth, income, and education were included in a Cox proportional hazards model to predict time to stroke.
Separate models were developed for the age groups 50 to 64, 65 to 74, and 75 and older, incorporating known stroke risk factors.
During a mean follow-up of 8.5 years, 1,542 participants had strokes.
Higher education predicted a reduced stroke risk in the age group of 50 to 64, but not after adjustment for wealth and income.
In contrast, wealth and income were independent predictors of stroke in that age group.
Participants in the lowest category for wealth (less than $1,000) and annual income ($5,657) had a relative stroke risk of 2.3 and 1.8, respectively, compared with participants in the highest category ($344,499 or more and $56,993 a year or more).
After adjustment, the hazard ratios for wealth (HR 1.7, 95% CI 1.2 to 2.5) and income (HR 1.6, 95% CI 1.2 to 2.3) remained significant.
Wealth, income, and education did not consistently predict stroke risk after age 65, however.
"The role of income and wealth may appear limited from a public health perspective because these factors are not related to stroke beyond age 65," the authors concluded.
"However," they said, "the age-attenuation of socioeconomic disparities in stroke likely reflects selective survival, a consequence of the cumulative disadvantage faced by individuals through the life-course."
"Policies that improve economically disadvantaged groups' access to basic resources before reaching old age might reduce stroke rates as these cohorts age," they said.
"Alternatively, enhancing opportunities for low socioeconomic status individuals to accumulate assets before retirement age might help reduce stroke rates and ameliorate socioeconomic status disparities in stroke."
The study was supported by the U.S. National Institute of Aging. The authors reported that they had no disclosures.

Primary source: StrokeSource reference:Avendano M, Glymour MM "Stroke disparities in older Americans. Is wealth a more powerful indicator of risk than income and education?" Stroke. 2008; DOI:10.1161/STROKEAHA.107.490383.

How Tainted Heparin Slipped Through U.S. Safety Net


By Michael Smith
BOSTON, 24 april 2008-- Researchers here revealed today how the adulterated heparin from China evaded detection at the U.S. border and how it killed scores of patients. Providing details of the episode that were previously disclosed by the FDA only in sweeping statements, the researchers confirmed that oversulfated chondroitin sulfate was the deadly culprit. In companion papers published online in Nature Biotechnology and the New England Journal of Medicine, Ram Sasisekharan, Ph.D., of the Massachusetts Institute of Technology, and colleagues in the U.S. and elsewhere also explained why the tainted heparin originally passed muster.
The researchers showed how the compound killed by activating two separate inflammatory pathways. They suggested that the methods they used to identify the compound might be employed by regulators to prevent a repetition.
The FDA said this week that 81 people have died in the U.S. as a result of contaminated heparin.
The tainted heparin slipped past regulators because current tests look for contaminants such as protein, lipids, or DNA, Dr. Sasisekharan and colleagues said.
But oversulfated chondroitin sulfate, derived from animal cartilage, is a long sugar molecule that is structurally similar to heparin and thus was not detected, the researchers said.
To tease out the nature of the contaminant, the researchers used nuclear magnetic resonance techniques to determine its characteristics, which they described as "highly unusual" owing to the presence of both a 3-O-sulfated glucuronic acid and a tetrasulfated disaccharide repeat unit.
They compared the NMR spectrum of the contaminant, derived from studying tainted samples, to that of freshly synthesized oversulfated chondroitin sulfate and found the two spectra matched.
It is "highly unlikely that the contaminant reported here is produced naturally," they said in Nature Biotechnology.
The study "provides the scientific groundwork for critical improvements in screening practices that can now be applied to monitor heparin, thus ensuring patient safety," Dr. Sasisekharan said in a statement.
To understand the biological effects of the contaminant, the researchers studied 29 clinical lots of heparin, including 13 associated with adverse events. In blinded tests, the 13 associated with adverse events were shown to contain the contaminant, compared with none of the control lots, they said in the NEJM.
In vitro tests showed that the contaminated heparin activated kallikrein amidolytic activity in human plasma, while control samples did not. Also, when the researchers purified oversulfated chondroitin sulfate from a contaminated sample, it had the same effect.
The kinin-kallikrein pathway can lead to the generation of bradykinin, a powerful vasoactive mediator, Dr. Sasisekharan and colleagues said.
To test the possible effects in vivo, they gave pigs intravenous injections (at 5 mg/kg) of heparin, contaminated heparin, synthetic oversulfated chondroitin sulfate, or chondroitin sulfate A.
Two of the six animals treated with contaminated heparin suffered at least a 30% drop in blood pressure over the first 30 minutes after infusion, they found, while those treated with synthetic oversulfated chondroitin sulfate had even more profound drops in blood pressure.
In contrast, Dr. Sasisekharan and colleagues said, none of the pigs given control heparin had any substantive changes in blood pressure.
The physiological changes were mirrored by rapid induction of the amidolytic activity of kallikrein, they said.
The researchers also showed in vitro that the contaminant can induce the generation of C3a and C5 anaphylatoxins.
"These results provide a potential link between the presence of chemical contaminant in heparin and the clinical symptoms observed in affected patients," Dr. Sasisekharan said.
Jeremy Berg, Ph.D., director of the National Institute of General Medical Sciences, called the research "vital for public health" and a "chemical triumph."
"The research team accomplished this difficult task by using a unique combination of scientific techniques that might in the future be used to detect other impurities in pharmaceutical materials," Dr. Berg said in a statement.
The research was supported by the National Institute of General Medical Sciences. Dr. Sasisekharan reported being a consultant for Scientific Protein Labs and Momenta Pharmaceuticals. He also holds equity in Momenta. Several other authors are employees of Momenta, which has technology aimed at analysis of complex mixtures.

Additional source: New England Journal of MedicineSource reference: Kishimoto TK, et al "Contaminated heparin associated with adverse clinical events and activation of the contact system" N Engl J Med 2008; 358: DOI: 10.1056/NEJMoa0803200. Additional source: Nature BiotechnologySource reference: Guerrini M, et al "Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events" Nature Biotech 2008; DOI:10.1038/nbt1407.

Octogenarians and Older May Benefit from Regular Mammography

By Todd Neale
HOUSTON, 24 april 2008-- For octogenarian women and older, regular screening mammography may translate into earlier breast cancer diagnoses and better disease-specific survival.
So revealed a retrospective database study of 12,358 women 80 or older with breast cancer, Gildy Babiera, M.D., of the University of Texas M. D. Anderson Cancer Center here, and colleagues, reported online in the Journal of Clinical Oncology. The study will be published in the May 20 print issue.
Each mammogram received within five years prior to diagnosis was associated with a 37% decreased risk of having late-stage (IIb to IV) disease (OR 0.63, 95% CI 0.63 to 0.67).
Five-year breast cancer-specific survival rates were 94% for regular mammography users, 88% for irregular users, and 82% for nonusers (P<0.0001).
However, non-breast cancer-related survival was also associated with mammography use, "suggesting a bias for healthier patients to undergo mammography," they said.
Nevertheless, they concluded, "healthcare providers should consider discussing the potential benefits of screening mammography with their older patients, particularly for those without significant comorbidity."
Randomized trials on the use of screening mammography have excluded patients older than 74, even though the proportion of the population who are 80 and older is growing, the researchers said.
Current guidelines on screening for breast cancer in older patients vary in their recommendations, with some considering life expectancy, a variable that is difficult to predict, they said.
Dr. Babiera and colleagues analyzed data from the Surveillance, Epidemiology, and End Results (SEER) -- Medicare linked database on women 80 and older who were diagnosed with breast cancer from 1996 through 2002.
Forty-nine percent of the patients had not had a screening mammography during the five years before diagnosis. Twenty-two percent had three or more screenings spaced at least 11 months apart (regular users) and 29% had one or two (irregular users).
From 1996 to 2002, regular mammography use increased from 17.2% to 25.8% and nonuse declined from 53% to 45.9%.
Whites and those who had more education, were married, and had a higher income were more likely to receive regular screenings.
Nonusers had poorer baseline health than regular users, as indicated by higher scores on the Charlson comorbidity index (P<0.0001).
Nonusers also had the highest mean tumor size (5.22 cm, 95% CI 4.57 to 5.86) compared with irregular (3.4 cm, 95% CI 2.70 to 4.10) and regular (2.9 cm, 95% CI 2.15 to 3.65) users.
Regular users had a larger percentage of stage I breast cancer compared with the rest of the cohort, and irregular and nonusers had higher percentages of stage II to IV disease.
Late-stage disease was more common among blacks (OR 1.71, 95% CI 1.45 to 2.02) and those of "other" race (OR 1.07, 95% CI 1.06 to 1.52) than among whites, even after adjusting for mammography use.
A score of 1 on the Charlson comorbidity index was also associated with higher likelihood of late-stage cancer (OR 1.48, 95% CI 1.30 to 1.69).
"Our findings are consistent with those of other reports demonstrating improvements in stage presentation for older women undergoing routine mammography, although none has focused specifically on individuals ≥80 years of age," the researchers said.
They acknowledged some limitations to the study, including the difficulty in separating screening and diagnostic mammography, the inability to account for screenings paid for outside of Medicare, and the fact that the patients in the database used in the study are more likely to be urban, affluent, and non-white compared with the general population.
They also pointed out the potential role of selection bias. "Specifically, this selection bias reflects the tendency for healthier patients, who have longer life expectancies, to undergo screening mammography."
"Despite these limitations," they said, "the SEER-Medicare database provides data on a large and geographically diverse population that can answer important questions pertaining to screening in the older adult population, especially in lieu of the exclusion of older adult populations from large controlled trials."

Primary source: Journal of Clinical OncologySource reference:Badgwell B, et al "Mammography before diagnosis among women age 80 years and older with breast cancer" J Clin Oncol 2008; DOI: 10.1200/JCO.2007.12.8058.

Glaxo Says Wine May Fight Aging

By ANDREW POLLACK
24 april 2008--Like many aging pharmaceutical companies, GlaxoSmithKline has been looking for rejuvenation. Now it thinks it might have literally found the elixir of youth.
Glaxo, a British drug maker, said Tuesday it would acquire an American biotechnology company that is pursuing the notion that a compound found in red wine might retard aging and let people live longer.
Glaxo will pay $720 million in cash, or $22.50 a share, for the company, Sirtris Pharmaceuticals. That is an 84 percent premium to Sirtris’s closing price Tuesday of $12.23.
Sirtris, based in Cambridge, Mass., was founded in 2004 after Dr. David Sinclair of Harvard Medical School found that a wine ingredient, resveratrol, made yeast live longer. Subsequently Dr. Sinclair, a co-founder of Sirtris, showed that the compound could counter the effects of a high-fat diet in mice and extend their lives.
Christoph Westphal, the chief executive of Sirtris, said Tuesday that drugs that mimic resveratrol, by activating enzymes called sirtuins, could “treat in a safe, natural new way, many of the major killers of western society.”
Because the Food and Drug Administration does not consider aging itself a disease, Sirtris is testing its compounds against illnesses associated with aging.
Two early-stage clinical trials provided preliminary evidence that Sirtris’s formulation of resveratrol could lower blood sugar in people with diabetes. Sirtris hopes to soon begin trials of a synthetic compound that is much more potent than resveratrol.
Glaxo and other drug companies have been paying high prices for biotech companies to bolster their drug pipelines.
Moncef Slaoui, chairman of Glaxo’s research and development arm, said Sirtris had “potentially transformative science.” Sirtris will remain an autonomous unit within Glaxo, with Dr. Westphal in charge.

Enzyme Beneficial to Alzheimer's Plays Darker Role in Other Dementia


24 april 2008-- An enzyme shown to help suppress development of Alzheimer's disease appears to hasten progress of a related but far less common type of dementia, according to a new study.
The surprising findings, published in the April 22 online issue of The Journal of Clinical Investigation, are significant, because individuals with frontotemporal dementia with parkinsonism-17 -- a relatively rare hereditary form of dementia -- are often used as models for studying Alzheimer's disease.
Alzheimer's disease and frontotemporal dementia each develop as a result of too many tau proteins accumulating and causing tangled lesions in the brain's neurons. These knotted nerve cells eventually choke off the brain cells responsible for memory.
However, individuals with frontotemporal dementia have mutations in the gene, known as P301L, encoding tau. These mutations have not been found in individuals with Alzheimer's.
Researchers found in mouse models and human cells that boosting levels of the prolyl isomerase (Pin1) enzyme, previously shown to aid in "detangling" tau in Alzheimer's disease, helps break down the tau proteins. However, the same experiments on mice with the genetic mutations in the tau that cause frontotemporal dementia resulted in increased and accelerated tau protein tangling.
"First, we have established a proof of concept that boosting Pin1 activity may offer a new idea for preventing or even treating the tau pathology and neurodegeneration in Alzheimer's disease," senior author Kun Ping Lu, a scientist in the Division of Hematology/Oncology at Beth Israel Deaconess Medical Center, said in a prepared statement. "And, second, given that no tau mutation is found in Alzheimer's patients, this research suggests that it would be prudent to not use P301L tau as an Alzheimer's disease model, especially when screening and testing drugs, as it may produce diametrically opposite effects."

Getting in and out of cars risky for seniors

By Anne Harding
24 april 2008--Older people should be careful when getting into cars, and even more so when getting out, a new analysis of national injury data shows.
An estimated 37,000 people 65 and older are injured each year when entering or exiting a vehicle, Dr. Ann M. Dellinger of the National Center for Injury Prevention and Control at the Centers for Disease Control and Prevention in Atlanta and her colleagues found. About 40 percent of these injuries were due to falls.
"I think it's important for people to be aware that there is a fall risk of getting into and out of a vehicle," Dellinger told Reuters Health. People 65 and older were more likely to be hospitalized as a result of these falls than younger individuals, she added.
The US population is getting older, Dellinger and her colleagues note in the Journal of the American Geriatrics Society. Meanwhile, the percentage of older adults with valid driver's licenses is on the rise, and seniors are spending more time on the road and logging more miles.
Both factors suggest that injuries entering and exiting cars, especially falls, could be a growing problem, the researchers add. To investigate, they looked at data for 2001 to 2003 from the National Electronic Injury Surveillance System-All Injury Program, which gathers injury data from 66 emergency rooms around the country.
The sample included 14,774 people of all ages who were injured getting out of or into a vehicle. People 65 and older were 10 times more likely to be hospitalized for these injuries than younger people, and women were significantly more likely to be hospitalized than men. Injuries were more than twice as likely to occur when a person was getting out of a vehicle than when he or she was entering the vehicle.
Falls don't have to be an inevitable consequence of aging, Dellinger emphasized in an interview. "It's important for people to know that there are absolutely some things they can do to prevent their risk of falls," she said.
There are four key steps people can take to protect themselves, she continued: exercising regularly; having a health professional review the medications they are taking; getting their vision checked; and making their home safer. "All of those things are effective fall protection interventions," she said.
The Centers for Disease Control and Prevention offers more information on fall prevention at www.cdc.gov/injury/ncipc/cuip/preventadultfalls.htm.
SOURCE: Journal of the American Geriatrics Society, April 2008.

UN official: Biodiversity loss could hurts medical research

By GILLIAN WONG
24 april 2008--The world risks losing new medical treatments for osteoporosis, cancer and other human ailments if it does not act quickly to conserve the planet's biodiversity, a senior United Nations environmental official said Wednesday.
Earth's organisms offer a variety of naturally made chemical compounds with which scientists could develop new medicines, but are under threat of extinction, said Achim Steiner, executive director of the U.N. Environment Program.
"We must do something about what is happening to biodiversity," Steiner told reporters. "We must help society understand how much we already depend on diversity of life to run our economies, our lives, but more importantly, what are we losing in terms of future potential."
Steiner was announcing the conclusions of a new medical book, "Sustaining Life," on the sidelines of a UNEP-organized conference in Singapore. The book is the work of more than 100 experts, its key authors based at Harvard Medical School's Center for Health and the Global Environment, and it underscores what may be lost to human health when species go extinct, Steiner said.
"Because of science and technology ... we are in a much better position to unlock this ingenuity of nature found in so many species," he said. "Yet, in many cases, we will find that we have already lost it before we were able to use it."
One example is the southern gastric brooding frog, or Rheobactrachus, which raises its young in the female's stomach. It was discovered in the Australian rainforests in the 1980s.
In other animals, the young would have been digested by enzymes and acids in the stomach. But preliminary studies show the baby frogs produced a substance or a range of substances that inhibited acid and enzyme secretions and prevent the mother from emptying her stomach into her intestines while the young were developing.
Research on this species of frog could have led to new insights into preventing and treating human peptic ulcers, but such studies could not be continued because the two species of Rheobactrachus had become extinct, according to the book.
Steiner said the book looks at seven groups of threatened organisms for potential or known medical value: amphibians, bears, cone snails, sharks, non-human primates, horseshoe crabs and gymnosperms, a type of plant life.
Last year, more than 16,000 species were labeled as threatened with extinction on the Swiss-based International Union for Conservation of Nature's Red List of Threatened Species.

Life Expectancy Is Declining in Some counties in the United States

By NICHOLAS BAKALAR
23 april 2008--Life expectancy has long been growing steadily for most Americans. But it has not for a significant minority, according to a new study, which finds a growing disparity in mortality depending on race, income and geography.
The study, published Monday in the online journal PLoS, analyzed life expectancy in all 3,141 counties in the United States from 1961 to 1999, the latest year for which complete data have been released by the National Center for Health Statistics. Although life span has generally increased since 1961, the authors reported, it began to level off or even decline in the 1980s for 4 percent of men and 19 percent of women.
“It’s very troubling that there are parts of the wealthiest country in the world, with the highest health spending in the world, where health is getting worse,” said Majid Ezzati, the lead author and an associate professor of international health at Harvard. It is a phenomenon, he added, “unheard of in any other developed country.”
Counties with significant declines were concentrated in Appalachia, the Southeast, Texas, the southern Midwest and along the Mississippi River. Life expectancy increases were mainly in the Northeast and on the Pacific Coast.
The researchers also compared the 2.5 percent of counties with the lowest life expectancies and the 2.5 percent with the highest. The disparity between those two groups rose to 11 years for men in 1999, from 9 years in 1983, and to 7.5 years from 6.7 in women.
The study found that from 1961 to 1983, there was little difference in average income for the counties where life expectancy rose at rates above and below the mean. But after 1983, life span rose with wealth. Race may also be a factor. In counties where life expectancy declined, the proportion of African-Americans was higher.
From 1961 to 1983, no county had a statistically significant decline in life expectancy, and reductions in cardiovascular disease led to a generally increasing length of life for both sexes. But after 1983, life expectancy declined an average of 1.3 years in 11 counties for men, and in 180 counties for women.
This lack of progress among the worst off was caused by a slowing or halt of reductions in cardiovascular disease, combined with increases in lung cancer and diabetes for women and in H.I.V. infection and homicide for men.
This rise in mortality for chronic diseases runs counter to trends in other developed countries, and the geographical differences are consistent with regional trends in smoking, high blood pressure and obesity. Dr. Ezzati speculates that data after 1999 will show more decreases in life span for the worst-off women. He expects to see a slight increase for men, with improved treatment for H.I.V. and AIDS.
“What’s driving the disparity is the worsening of the worst off,” Dr. Ezzati said. “In the U.S., there has always been a view, stated or unstated, that we can live with some inequality if everyone is getting better. This is the first sign that not everyone is getting better.”

more information:

The Reversal of Fortunes: Trends in County Mortality and Cross-County Mortality Disparities in the United States : http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371%2Fjournal.pmed.0050066&ct=1

It's no LOL: Few US doctors answer e-mails from patients

By ALICIA CHANG
23 april 2008--Suzanne Kreuziger is a registered nurse who uses e-mail almost exclusively to communicate with friends. But when it comes to reaching her doctor, there's a frustrating firewall.
The barrier is her doctor's own reluctance to talk to patients through e-mail.
"It makes sense to me to have the words laid out, to be able to re-read, to go back to it at a convenient time," the 34-year-old Milwaukee woman recently wrote on a social networking site. "If I were able to ask my physician questions this way, it would make my own health care much easier."
Kreuziger's experience is shared by most Americans: They want the convenience of e-mail for non-urgent medical issues, but fewer than a third of U.S. doctors use e-mail to communicate with patients, according to recent physician surveys.
"People are able to file their taxes online, buy and sell household goods, and manage their financial accounts," said Susannah Fox of the Pew Internet & American Life Project. "The health care industry seems to be lagging behind other industries."
Doctors have their reasons for not hitting the reply button more often. Some worry it will increase their workload, and most physicians don't get reimbursed for it by insurance companies. Others fear hackers could compromise patient privacy — even though doctors who do e-mail generally do it through password-protected Web sites.
There are also concerns that patients will send urgent messages that don't get answered promptly. And any snafu raises the specter of legal liability.
Many patients would like to use e-mail for routine matters such as asking for a prescription refill, getting lab results or scheduling a visit. Doing so, they say, would help avoid phone tag or taking time off work to come in for a minor problem.
Still, a survey conducted early last year by Manhattan Research found that only 31 percent of doctors e-mailed their patients in the first quarter of 2007.
Two major health insurers, Cigna Corp. and Aetna Inc., this year expanded pilot programs that compensate doctors who use a secure Internet site to make virtual house calls with patients. That includes the ability to send encrypted e-mail, a move some hope will increase the number of doctors who go digital.
Dr. Daniel Z. Sands, an assistant clinical professor at Harvard Medical School, is among the early adopters who doesn't get paid for e-visits. He sees communicating with patients online as no different from phoning them, a practice that also is not billable.
Since 2000, Sands has answered patient questions by logging onto a password-protected Web site of the Harvard-affiliated Beth Israel Deaconess Medical Center. He also sets his Treo to retrieve new messages every four hours. He mostly gets e-mails from patients seeking advice for new symptoms or updates from chronic disease sufferers.
Although Sands has had mostly positive experiences, one patient bombarded him with e-mails. She became "pushy" and her messages were sometimes threatening.
"We sort of had this fight back and forth through electronic communication, which is absolutely the wrong thing to do. I should have picked up the phone and called her. Any message that takes more than two volleys back and forth should not be done by e-mail," Sands said.
The American Medical Association says e-mail should not replace face-to-face time with patients. The group's etiquette guidelines recommend talking to patients about the technology's limitations.
Most studies have shown patients don't abuse e-mail. They generally don't deluge doctors with rambling messages, and Internet exchanges may even help doctors' productivity and cut down on office visits.
For example, a 2007 University of Pittsburgh study published in the journal Pediatrics followed 121 families who e-mailed their doctors. Researchers found 40 percent of e-mails were sent after business hours and only about 6 percent were urgent. Doctors received on average about one e-mail a day and responded 57 percent faster than by telephone.
A separate study by health care giant Kaiser Permanente published in the American Journal of Managed Care last year found patients who used its secure Web system were 7 to 10 percent less likely to schedule an office visit. Patients also made 14 percent fewer phone calls than those who did not use the online services.
Before e-mail can become as routine as a physical, doctors need to be trained to handle confidential patient messages in the digital age, some experts say. That would include learning to file e-mails in patients' health records and instructing patients in the risks of electronic messaging.
Kreuziger, the nurse who can't e-mail her doctor, works in a large practice that also doesn't offer e-mail services. She often has to phone patients to check on their blood-sugar levels or track them down about an abnormal lab test — a chore for a person who prefers e-mail over the phone.
"I hate a ringing phone. It's an interruption," she said in an interview.
Kreuziger and her colleagues recently asked patients about their Internet needs. Of the 76 patients who responded to the questionnaire, most said they would like e-mail access to their doctors.
It's not the first time the medical field has been slow to embrace technology. When the first telephones became widely available in the late 1800s, doctors were concerned about being swamped with calls.
Dr. Tom Delbanco, a primary care doctor at Beth Israel who e-mails patients, believes it is just a matter of time before the technology becomes a routine part of patient care.
"Medicine is very conservative. It changes slowly," he said.

Obesity, smoking cuts many US women's life expectancy: study

23 april 2008--Life expectancy has declined for many women in the United States, largely due to smoking-related diseases and obesity, a study published Tuesday showed.
Nearly one in five US women saw the number of years they are expected to live decline or hold steady, starting in the 1980s, showed the joint study by the Harvard School of Public Health and the University of Washington.
The study looked at data from more than 2,000 county "units" between 1959 and 2001.
In around 1,000 of those counties -- mainly poor, rural areas -- life expectancy for women dropped starting in the 1980s, "primarily because of chronic diseases related to smoking, overweight and obesity, and high blood pressure," according to the study.
In the United States as a whole, in contrast, life expectancy for women rose by more than six years and for men by more than seven years during the same period, it showed.
"There is now evidence that there are large parts of the population in the United States whose health has been getting worse for about two decades," Majid Ezzati, associate professor of international health at the Harvard School of Public Health, and lead author of the study, said in a statement.
Worst affected by the downturn in longevity were the south -- the region hardest hit by poverty, according to the US Census Bureau -- the Appalachians, southern parts of the Midwest and areas of Texas.
Men in the same areas also saw a drop in life expectancy, but numbers were less alarming than among women -- only four percent -- and the fall was attributed to different causes, mainly HIV/AIDS and homicide.
"Life expectancy decline is something that has traditionally been considered a sign that the health and social systems have failed, as has been the case in parts of Africa and Eastern Europe," said the study's co-author Christopher Murray, director of the Institute for Health Metrics and Evaluation at the University of Washington.
"The fact that this is happening to a large number of Americans should be a sign that the US health system needs serious rethinking," he added.

Panel says link between smog and premature death is clear

By H. JOSEF HEBERT
23 april 2008--Short-term exposure to smog, or ozone, is clearly linked to premature deaths that should be taken into account when measuring the health benefits of reducing air pollution, a National Academy of Sciences report concluded Tuesday.
The findings contradict arguments made by some White House officials that the connection between smog and premature death has not been shown sufficiently, and that the number of saved lives should not be calculated in determining clean air benefits.
The report by a panel of the Academy's National Research Council says government agencies "should give little or no weight" to such arguments.
"The committee has concluded from its review of health-based evidence that short-term exposure to ambient ozone is likely to contribute to premature deaths," the 13-member panel said.
It added that "studies have yielded strong evidence that short-term exposure to ozone can exacerbate lung conditions, causing illness and hospitalization and can potentially lead to death."
The White House Office of Management and Budget, which in its review of air quality regulations has raised questions about the certainty of the pollution and mortality link, did not immediately return a phone call seeking comment.
"The report is a rebuke of the Bush administration which has consistently tried to downplay the connection between smog and premature death," said Frank O'Donnell, president of Clean Air Watch, a Washington-based advocacy organization.
Vickie Patton, deputy general counsel for the Environmental Defense Fund, said the Academy's findings "refutes the White House skepticism and denial" of a proven link between acute ozone exposure and premature deaths. Such arguments have been used to diminish the health benefits of reducing air pollution, she said.
The Academy panel examined short-term exposure — up to 24 hours — to high levels of ozone, but said more studies also were needed on long-term chronic exposure where the risk of premature death "may be larger than those observed in acute effects studies alone."
Ground-level ozone is formed from nitrogen oxide and organic compounds created by burning fossil fuels and is demonstrated often by the yellow haze or smog that lingers in the air. Ozone exposure is a leading cause of respiratory illnesses and especially affects the elderly, those with respiratory problems and children.
While premature death from ozone exposure is greater among individuals with lung and heart disease, the report said such deaths are not restricted to people who are at a high risk of death within a few days.
The scientists said they could not determine, based on a review of health studies, whether there is a threshold below which no fatalities can be assured from ozone exposure. If there is such a point, it is below the ozone levels allowed for public health.
Environmentalists and health advocates have argued that a string of health studies and surveys show that exposure to smoggy air not only aggravates respiratory problems, but causes thousands of deaths a year.
But in a number of instances the EPA and the White House Office of Management and Budget, which reviews regulations, have been at odds over the certainty of a link between smog levels and deaths.
Patton said the OMB in a number of air pollution regulations has sought to minimize the relationship of pollution and premature deaths, resulting in a lower calculation of health benefits from pollution reductions.
"This has been used by industry to try to attack health standards by minimizing the societal benefits," said Patton.
One such case involves the EPA's decision last month to toughen the ozone health standard, reducing the allowable concentration in the air.
When the cost-benefit analysis was being prepared in connection with the rulemaking, the OMB argued there is "considerable uncertainty" in the association between ozone levels and deaths.
As a result, the EPA issued a wide cost-benefit range from an annual net societal cost of $20 billion to a savings of $23 billion, depending largely on whether one takes into account lives saved from ozone-related premature deaths.
OMB officials also have objected to the EPA quantifying ozone-related mortality benefits in new emissions standards for lawn mowers and other small engines that release large amounts of ozone-forming pollution.
In response, the EPA removed "all references to quantified ozone benefits" in the proposed rule, according to an e-mail sent by EPA to the OMB. The small engine regulation is awaiting final action.

Protein that cuts malignancy of breast cancer discovered

23 april 2008--Researchers have discovered a protein which can reduce the malignancy of breast cancer tumors and also predict whether the cancer will metastasize, according to a study published Monday.
"This protein seems to be suppressing tumor growth," said study author Kent Hunter of the National Cancer Institute outside of Washington.
In studies on mice and in gene expression profiles of human cancer cells, Hunter and his team found that they could dramatically slow the growth of breast cancer tumors and prevent the cancer from spreading.
They did this by inserting extra copies of the gene that expresses the protein into the tumor, according to the study published in the Proceedings of the National Academy of Sciences.
While those tumors were not eliminated, they grew to one tenth of the size of those which had not been stimulated to overproduce the protein.
They also had molecular profiles of significantly less malignant tumors and did not spread.
"What we're interested in is looking at how this would be induced by other means... to find a drug that would turn this gene on in tumors," Hunter said. "That would reduce the malignancy of the tumor and prolong survival."
In the meantime, the presence, or lack thereof, of this protein could be used to predict which patients are at risk of metastasis, he said.
"We could hopefully spare those patients who will not benefit the rigors associated with adjuvant therapy," he explained.
While there are at least two gene expression profiles currently in clinical trials to test the risk of metastasis, researchers have not yet teased out the root cause of those gene expressions.
"We know what the root cause of this gene expression change: that is this protein," Hunter told AFP.
"That gives us a handle on how we can investigate what is causing all these particular gene expression signatures and allows us potentially to do molecular targeting down the line that might somehow affect the cancer."
Any type of clinical application is still far away, he cautioned.

Many Cancer Survivors Are Overweight and Sedentary: Study

By Serena Gordon
21 april 2008-- A healthy lifestyle may help cancer survivors prevent recurrence of the disease and live longer, yet cancer survivors have rates of obesity and physical inactivity similar to those of the general population, according to new research.
The study, published in the June 1 issue of Cancer, found that less than one-quarter of cancer survivors were regularly physically active, and more than 18 percent were obese.
"We thought this might be a time when people would be particularly motivated to exercise and control weight. But, a cancer diagnosis and treatment didn't seem to stimulate behavior change," said the study's lead author, Kerry Courneya, a professor and Canada Research Chair at the University of Alberta in Edmonton, Canada.
What's troubling is that maintaining a healthy weight and getting regular physical exercise may be even more crucial for cancer survivors than it is for the general public. Some studies have suggested that physical activity and losing weight may help prevent cancer recurrence and improve survival odds.
Additionally, some research suggests that exercise can help reduce fatigue, improve physical functioning and improve quality of life for some cancer survivors.
For the study, Courneya and his colleagues gathered data from the Canadian Community Health Survey. This survey contains information based on interviews of more than 114,000 people in Canada. Details of cancer history, weight, height and physical activity were all supplied by the respondents.
General population statistics for Canada find that 37 percent of people are overweight, and 22 percent are obese, according to background information in the study.
Fewer than 22 percent of cancer survivors reported being physically active. The lowest rates of physical activity were found among colorectal cancer survivors, breast cancer survivors and female survivors of melanoma.
Thirty-four percent of cancer survivors were overweight, and almost one in five was obese.
Obese breast cancer survivors were only about half as likely to be physically active as obese women who hadn't had cancer, a finding that's particularly worrisome, because poor outcomes in breast cancer have been associated with obesity and the often accompanying sedentary lifestyle.
"We really didn't know which way the research would go. Cancer survivors may be more motivated at the time of their diagnosis to make changes, but others point out that it's a very stressful time that can take a toll and lead to the opposite effect," Courneya said.
Kevin Stein, director of Quality of Life Research at the American Cancer Society, said, "This is an important finding to underscore the fact that cancer survivors need to pay attention to their health. You've dodged a bullet for the time being, but cancer survivors are actually at an increased risk for a number of health conditions, including cancer recurrence.
"There is a teachable moment when someone is diagnosed. It's the perfect opportunity to say, 'We all need to eat healthy and exercise, but it's even more important for you as a cancer survivor,' " he said.
Courneya added: "This is something they can do for themselves to help beat cancer and improve quality of life. The cancer community needs to get more involved in the promotion of healthy lifestyles in cancer patients. Maybe a program something like cardiac rehabilitation. The cancer community's been slower to realize the importance of lifestyle changes after cancer diagnosis."