Cyberchondria: Studies of the Escalation of Medical Concerns in Web Search

by Ryen White; Eric Horvitz
30 nov 2008--The World Wide Web provides an abundant source of medical information. This information can assist people who are not healthcare professionals to better understand health and disease, and to provide them with feasible explanations for symptoms. However, the Web has the potential to increase the anxieties of people who have little or no medical training, especially when Web search is employed as a diagnostic procedure. We use the term cyberchondria to refer to the unfounded escalation of concerns about common symptomatology, based on the review of search results and literature on the Web. We performed a large-scale, longitudinal, log-based study of how people search for medical information online, supported by a large-scale survey of 515 individuals’ health-related search experiences. We focused on the extent to which common, likely innocuous symptoms can escalate into the review of content on serious, rare conditions that are linked to the common symptoms. Our results show that Web search engines have the potential to escalate medical concerns. We show that escalation is influenced by the amount and distribution of medical content viewed by users, the presence of escalatory terminology in pages visited, and a user’s predisposition to escalate versus to seek more reasonable explanations for ailments. We also demonstrate the persistence of post-session anxiety following escalations and the effect that such anxieties can have on interrupting user’s activities across multiple sessions. Our findings underscore the potential costs and challenges of cyberchondria and suggest actionable design implications that hold opportunity for improving the search and navigation experience for people turning to the Web to interpret common symptoms.

Caffeinated Coffee Linked to Lower Heart Disease Risk

Association found in elderly subjects with mild or better hypertension

30 nov 2008-- Elderly individuals who drink at least one cup of caffeinated coffee a day have a lower risk of coronary heart disease if they have mild or better hypertension, researchers report in the Dec. 1 issue of the American Journal of Cardiology.
James A. Greenberg, Ph.D., from Brooklyn College of the City University of New York, and colleagues examined the association between caffeinated coffee consumption and heart disease morbidity and mortality using data from 1,354 individuals aged 65 years and older. Caffeinated coffee consumption was determined through a food-frequency questionnaire.
During 10.1 years of follow-up, the researchers documented 210 deaths from cardiovascular disease and 118 from coronary heart disease. There was a significant negative association between caffeinated coffee intake and coronary heart disease in individuals with mild hypertension or better (systolic blood pressure less than 160 mm Hg and diastolic blood pressure less than 100 mm Hg), the investigators found. Individuals who consumed at least one cup of caffeinated coffee per day had a 43 percent lower risk of coronary heart disease than those who did not drink caffeinated coffee, which appeared to be due to a 43 percent reduced risk of heart valve disease, the report indicates.
"Caffeinated coffee consumption was associated with lower risk of coronary heart disease mortality and heart valve disease development or progression in older…subjects without moderate or severe hypertension," Greenberg and colleagues conclude.

Cardiac CT Angiography No Substitute for Conventional Procedure

By Crystal Phend
BALTIMORE, 30 nov 2008-- Cardiac CT angiography misclassifies diagnosis of coronary stenosis in too many patients to replace conventional invasive imaging, researchers here said. The noninvasive technique had a diagnostic accuracy of 93% for coronary obstruction and identified patients who subsequently underwent revascularization at least as well as conventional angiography (area under the curve 0.84 versus 0.82, P=0.36), Joao A.C. Lima, M.D., of Johns Hopkins Hospital, and colleagues found in a prospective, international trial of symptomatic patients. But CT angiography's positive predictive value of 91% and a negative predictive value of 83% didn't measure up, they reported in the Nov. 27 issue of the New England Journal of Medicine.
The 13% misclassification indicates that "multidetector CT angiography cannot be used as a simple replacement for conventional coronary angiography," they wrote.
These findings add to the body of research that fails to prove a benefit of the newer technology, said Rita F. Redberg, M.D., and Judith Walsh, M.D., M.P.H., both of the University of California San Francisco, in an accompanying commentary.
Earlier studies on CT angiography have had widely varying results for determining coronary obstruction, likely because of limitations in selection of patients, small sample size, single-center study design, and CT technology, the investigators noted.
So, they conducted the prospective CORE 64 diagnostic study at nine hospitals in the U.S. and six other countries.
The study compared 64-row, 0.5-mm multidetector CT angiography and conventional coronary angiography in 291 patients referred for conventional angiography because of suspected symptomatic coronary artery disease.
Participants underwent blinded calcium scoring and CT angiography before conventional coronary angiography. Only those with calcium scores of 600 or less were included in the study because of known problems with artifacts in highly calcified vessels.
Compared with conventional angiography, the findings for CT angiography included:
An area under the receiver-operating-characteristic curve of 0.93 for the diagnosis of a patient with at least one coronary stenosis of 50% or more (95% confidence interval 0.90 to 0.96)
Sensitivity of 85% for obstructive stenosis of 50% or more (95% CI 79 to 90)
Specificity of 90% for obstructive stenosis of 50% or more (95% CI 83 to 94)
Positive and negative predictive values of 91% (95% CI 86 to 95) and 83% (95% CI 75 to 89), respectively, for a disease prevalence of 56%
Cardiac CT angiography had similar accuracy whether assessment of stenosis severity was visual or quantitative (AUC 0.93 for both, P=0.69).
Likewise, analysis by vessel rather than by patient showed an AUC of 0.91 (95% CI 0.88 to 0.93).
The newer technique also appeared to be accurate for determining the extent of coronary artery obstruction with good correlation between disease severity ascertained by CT and conventional angiography (r=0.81, 95% CI 0.76 to 0.84).
The 30-day rate of revascularization on the basis of obstructive stenoses revealed by the two angiography techniques was similar as well (AUC 0.84 with CT angiography [95% CI, 0.79 to 0.88] and 0.82 with invasive angiography [95% CI, 0.77 to 0.86], P=0.36).
The results of the study, however, do not advance knowledge of the appropriate use and possible benefits of the technology, wrote Drs. Redberg and Walsh in their commentary. "Because all patients received both cardiac CT angiography and conventional coronary angiography and no data on outcomes are reported, the study does not answer this important question."
They also noted that, without evidence of outcome benefit, "a high resolution cardiac CT angiographic image of the heart is just another pretty picture."
Also at issue, according to Drs. Redberg and Walsh, is the fact that cardiac imaging leads to additional unnecessary procedures and, worse, the "equipment bombards patients with radiation many orders of magnitude greater that that of traditional radiographs."
Dr. Lima's group emphasized, too, that their findings could not answer questions of use in asymptomatic patients. They cautioned that the results should not be used to support screening for asymptomatic coronary artery disease.
"Further studies are needed to define the method's precise role in the diagnostic algorithm for the evaluation of patients with suspected coronary artery disease," the researchers concluded.
The study was supported by grants from Toshiba Medical Systems; the Doris Duke Charitable Foundation; the National Heart, Lung, and Blood Institute; the National Institute on Aging; and the Donald W. Reynolds Foundation.
Dr. Lima and several coauthors reported receiving grant support and speakers' fees from Toshiba Medical Systems. Dr. Lima also reported grant support from GE Medical Systems while coauthors reported other conflicts of interest for Bayer, Schering, GE Healthcare, Bracco, Vital Images, Toshiba Medical Systems, GE Biosciences, CT Core Laboratory, Bristol-Myers Squibb, and sanofi-aventis.
Dr. Redberg reported receiving grant support from the Blue Shield of California Foundation.
Dr. Walsh reported no conflicts of interest.
Primary source: New England Journal of MedicineSource reference:Miller JM, et al "Diagnostic performance of coronary angiography by 64-row CT" N Engl J Med 2008; 359: 2324-36. Additional source: New England Journal of MedicineSource reference: Redberg RF, Walsh J "Pay now, benefits may follow -- the case of cardiac computed tomographic angiography" N Engl J Med 2008; 359: 2309-11.

Gasping After Cardiac Arrest Associated with Improved Survival

By Todd Neale
TUCSON, Ariz.,30 nov 2008- Out-of-hospital cardiac arrest patients who gasp or have labored breathing derive the most survival benefit from immediate chest compressions, a retrospective analysis showed.
Of patients who received compressions from a bystander, those who were gasping were more likely to survive to hospital discharge than those who were not breathing at all (39% versus 9.4%; OR 5.1, 95% CI 2.7 to 9.4), Gordon Ewy, M.D., of the University of Arizona, and colleagues reported online in Circulation: Journal of the American Heart Association.
"Gasping is an indication that the brain is still alive," Dr. Ewy said, "and it tells you that if you start and continue uninterrupted chest compressions, the person has a high chance of surviving."
Witnesses to cardiac arrest sometimes interpret gasping as normal breathing and don't call 911 or start chest compressions as quickly as they should, according to the researchers.
"These results suggest that the recognition and importance of gasping should be taught to bystanders and emergency medical dispatchers so as not to dissuade them from initiating prompt resuscitation efforts when appropriate," the researchers said.
This is especially important because chest compressions may cause a patient to begin gasping, Dr. Ewy said.
"This scares many people and they stop pressing on the chest," he said. "This is bad because gasping is an indication that you're doing a good job."
To determine the occurrence of gasping after out-of-hospital cardiac arrest, the researchers examined transcripts from the Phoenix Fire Department Regional Dispatch Center.
Of 113 patients who had a witnessed or non-witnessed cardiac arrest, 38.9% gasped or had labored breathing.
In a separate analysis, the researchers looked at emergency medical services' first-care reports of 1,218 patients who had a witnessed cardiac arrest.
Overall, 191 gasped and 1,027 didn't. The two groups did not differ significantly by age, arrest location, or receipt of bystander CPR.
For those who collapsed after EMS personnel arrived, 32.8% started gasping.
Rates of gasping declined as arrival time increased. There were 20.1% who had labored breathing when the arrival time was less than seven minutes, 13.9% when it was seven to nine minutes, and 7.4% when it was greater than nine minutes.
Gasping was significantly more common in the witnessed ventricular fibrillation group than in patients who had a witnessed arrest with a different rhythm (18.4% versus 13.6%; OR 1.7, 95% CI 1.2 to 2.4).
Survival to hospital discharge was significantly higher in patients who had some residual breathing than in those who did not (28.3% versus 7.8%; OR 3.4, 95% CI 2.2 to 5.2).
Of patients who were gasping when EMS personnel arrived, those who were receiving chest compressions from a bystander were more likely to survive than those who were not (39% versus 21%, P<0.01).
Patients who had gasping or labored breathing still had a survival advantage even if they weren't receiving CPR from a bystander (21.1% versus 6.7%; OR 2.4, 95% CI 1.2 to 4.3).
The researchers said that the results call into question the importance of rescue breathing for cardiac arrest patients, especially in light of previous findings of no survival benefit from rescue breathing.
"Interruptions for rescue breathing make CPR efforts more complicated and result in fewer compressions during this crucial period when perfusion is key to successful resuscitation," they said.
In addition, gasping is likely more beneficial than rescue breathing, Dr. Ewy said.
"When the patient gasps, there is a negative pressure in the chest, which not only sucks air into the lungs but also draws blood back to the heart," he explained.
"In contrast, mouth-to-mouth breathing creates overpressure in the chest and actually inhibits blood flow back to the heart," he continued. "Gasping during cardiac arrest is much better than mouth-to-mouth breathing."
The authors acknowledged that the study was limited by the possibility that the EMS reports did not accurately record the presence or absence of gasping.
In addition, they said, gasping is not diagnostic of ventricular fibrillation arrest.
Dr Bobrow has received salary support from the Arizona Department of Health Services via the Mayo Clinic Foundation for support of his position as medical director of the Bureau of Emergency Medical Services and Trauma System. Dr Ewy is a co-investigator on an unrestricted grant from the Laerdal Foundation of Stavanger, Norway, and on unrestricted grants to the University of Arizona Foundation. The other authors reported potential conflicts of interest with the Anaesthesieverein of the Department of Anesthesia and Intensive Care of University Hospital in Basel, Switzerland, the Laerdal Foundation, the National Heart, Lung, and Blood Institute, Medtronic, the AHA National Registry of CPR, Zoll, and PhysioControlInc.
Primary source: Circulation: Journal of the American Heart AssociationSource reference:Bobrow B, et al "Gasping during cardiac arrest in humans is frequent and associated with improved survival" Circulation 2008; DOI: 10.1161/CIRCULATIONAHA.108.799940. Additional Coronary Artery Disease Coverage

FDA Approves Dual-Action Analgesic for Moderate to Severe Acute Pain

By Peggy Peck
ROCKVILLE, 30 nov 2008-- The FDA announced today it has approved a centrally acting oral analgesic, Tapentadol hydrocholoride, for relief of moderate to severe acute pain.
The drug combines mu-opioid receptor agonism with norepinephrine reuptake inhibition in a single molecule.
The FDA approved an immediate release formulation of the drug in 50-mg, 75-mg, and 100-mg doses.
The agency said the approval offered "health care professionals an additional choice for treating moderate to severe acute pain."
The most common side effects reported with Tapentadol were nausea, dizziness, vomiting, sleepiness, and headaches.
The FDA said the Tapentadol label will include warnings about the risk of respiratory depression; addictive depressive effects on the central nervous system when taken with alcohol, other opioids, or illicit drugs; and abuse potential.
The drug is marketed by Johnson & Johnson of New Brunswick, N.J.

The Minimal Impact of a Big Hypertension Study

By ANDREW POLLACK
29 nov 2008--The surprising news made headlines in December 2002. Generic pills for high blood pressure, which had been in use since the 1950s and cost only pennies a day, worked better than newer drugs that were up to 20 times as expensive.
The findings, from one of the biggest clinical trials ever organized by the federal government, promised to save the nation billions of dollars in treating the tens of millions of Americans with hypertension — even if the conclusions did seem to threaten pharmaceutical giants like Pfizer that were making big money on blockbuster hypertension drugs.
Six years later, though, the use of the inexpensive pills, called diuretics, is far smaller than some of the trial’s organizers had hoped.
“It should have more than doubled,” said Dr. Curt D. Furberg, a public health sciences professor at Wake Forest University who was the first chairman of the steering committee for the study, which was known by the acronym Allhat. “The impact was disappointing.”
The percentage of hypertension patients receiving a diuretic rose to around 40 percent in the year after the Allhat results were announced, up from 30 to 35 percent beforehand, according to some studies. But use of diuretics has since stayed at that plateau. And over all, use of newer hypertension drugs has grown faster than the use of diuretics since 2002, according to Medco Health Solutions, a pharmacy benefits manager.
The Allhat experience is worth remembering now, as some policy experts and government officials call for more such studies to directly compare drugs or other treatments, as a way to stem runaway medical costs and improve care.
The aftereffects of the study show how hard it is to change medical practice, even after a government-sanctioned trial costing $130 million produced what appeared to be solid evidence.
A confluence of factors blunted Allhat’s impact. One was the simple difficulty of persuading doctors to change their habits. Another was scientific disagreement, as many academic medical experts criticized the trial’s design and the government’s interpretation of the results.
Moreover, pharmaceutical companies responded by heavily marketing their own expensive hypertension drugs and, in some cases, paying speakers to publicly interpret the Allhat results in ways that made their products look better.
“The pharmaceutical industry ganged up and attacked, discredited the findings,” Dr. Furberg said. He eventually resigned in frustration as chairman of the study’s steering committee, the expert group that continues to oversee analysis of data from the trial. One member of that committee received more than $200,000 from Pfizer, largely in speaking fees, the year after the Allhat results were released.
There was another factor: medicine moves on. Even before Allhat was finished, and certainly since then, new drugs appeared. Others, meanwhile, became available as generics, reducing the cost advantage of the diuretics. And many doctors have shifted to using two or more drugs together, helped by pharmaceutical companies that offer combination pills containing two medicines.
So Allhat’s main query — which drug to use first — became “an outdated question that doesn’t have huge relevance to the majority of people’s clinical practices,” said Dr. John M. Flack, the chairman of medicine at Wayne State University, who was not involved in the study and has consulted for some drug makers.
Dr. Sean Tunis, a former chief medical officer for Medicare, remains an advocate for comparative-effectiveness studies. But, as Allhat showed, “they are hard to do, expensive to do and provoke a lot of political pushback,” said Dr. Tunis, who now runs the nonprofit Center for Medical Technology Policy, which tries to arrange such trials.
“There’s a lot of magical thinking,” he said, “that it will all be science and won’t be politics.”
Expensive Pills
Promising better ways to treat high blood pressure, drug companies in the 1980s introduced a variety of medications, including ones known as calcium channel blockers and ACE inhibitors.
Although there was no real evidence the newer pills were better, diuretics fell to 27 percent of hypertension prescriptions in 1992, from 56 percent in 1982. Use of the more expensive pills added an estimated $3.1 billion to the nation’s medical bill over that period.
So the National Heart, Lung and Blood Institute, part of the federal National Institutes of Health, decided to compare the various drugs’ ability to prevent heart attacks, strokes and other cardiovascular problems. “This was a big-bucks issue,” said Dr. Jeffrey Cutler, the Heart, Lung and Blood Institute’s project director for the study.
Allhat — short for the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial — began enrolling patients with high blood pressure, age 55 and older, in 1994, with more than 42,000 people eventually participating. Patients were randomly assigned one of four drugs: a diuretic called chlorthalidone; an ACE inhibitor called lisinopril, which AstraZeneca sold as Zestril; a calcium channel blocker, amlodipine, sold by Pfizer as Norvasc; and an alpha blocker, doxazosin, which Pfizer sold as Cardura.
Cardura was added only after Pfizer, which had already agreed to contribute $20 million to the trial’s costs, increased that to $40 million, Dr. Cutler said.
Early Trouble Signs
Pfizer’s bet on Cardura proved a big mistake. As the Allhat data came in, patients taking Cardura were nearly twice as likely as those receiving the diuretic to require hospitalization for heart failure, a condition in which the heart cannot pump blood adequately. Concerned, the Heart, Lung and Blood Institute announced in March 2000 that it had stopped the Cardura part of the trial.
What happened next provided the first signs that the Allhat evidence might not be universally embraced.
Rather than warn doctors that Cardura might not be suited for hypertension, Pfizer circulated a memo to its sales representatives suggesting scripted responses they could use to reassure doctors that Cardura was safe, according to documents released from a patients’ lawsuit against the company.
And in an e-mail message unearthed in those same court documents, a Pfizer sales executive boasted to colleagues that company employees had diverted some European doctors attending an American cardiology conference from hearing a presentation on the Allhat results and Cardura. “The good news,” the message said, “is that they were quite brilliant in sending their key physicians to sightsee rather than hear Curt Furberg slam Pfizer once again!”
Pfizer declined to comment on the messages.
The Food and Drug Administration waited a year before convening a meeting of outside experts to discuss Cardura’s safety. At that session, some of the experts sharply challenged the conclusions of the Allhat organizers. They argued that the heart failure cases might have been false readings and that an inadequate dose of Cardura had been used in the trial.
By the end of the daylong meeting, Dr. Robert J. Temple, a senior F.D.A. official, was clearly exasperated by the experts’ varying interpretations of a supposedly definitive trial.
“This is the largest and best attempt to compare outcomes we are ever going to see,” he said. “And people are extremely doubtful about whether it has shown anything at all.”
The committee decided that there was no need to issue an urgent warning to doctors and patients about Cardura.
Cardura sales held up in 2000. But the next year, worldwide sales fell to $552 million, from $795 million. Prescriptions for all alpha blockers fell 22 percent from 1999 to 2002 after having risen before then, according to one study.
Pfizer’s decision to stop promoting Cardura in late 2000, after the drug lost patent protection, was a factor in the decline. But Allhat clearly was, too.
Cost-Benefit Analysis
The main Allhat results were announced in December 2002 at a news conference in Washington and published in The Journal of the American Medical Association.
In the primary target outcome of the trial — the prevention of heart attacks — the three remaining drugs were proved equal. But patients receiving the Norvasc calcium channel blocker from Pfizer had a 38 percent greater incidence of heart failure than those on the diuretic. And those receiving the ACE inhibitor from AstraZeneca had a 15 percent higher risk of strokes and a 19 percent higher risk of heart failure.
Moreover, the diuretic cost only about $25 a year, compared with $250 for an ACE inhibitor and $500 for a calcium channel blocker. So the diuretic was declared the winner.
But some hypertension experts accused the government of overstating the case for the diuretics, as a way to cut medical spending.
“There was a feeling there was a political and economic agenda as much as a scientific agenda,” said Dr. Michael Weber, a professor of medicine at the Health Science Center at Brooklyn, part of the State University of New York, who had been an investigator in the study but afterward became one of its leading critics. “They pushed beyond what the data allowed them to say.”
Critics said the rules of the trial had favored the diuretics. If the first drug did not adequately lower blood pressure — as happened in more than 60 percent of cases — a second drug could be added. But that second drug was usually a type that worked better with diuretics than with ACE inhibitors.
There were also more new cases of diabetes among the patients who took diuretics, although experts argued over how meaningful that finding was.
Adding fuel to the debate, an Australian study released two months after Allhat found an ACE inhibitor superior to a diuretic. The proper lesson to draw from Allhat, some critics contended, was that what matters most is how much blood pressure is lowered, not which drug is used to do it. For these and other reasons, European hypertension experts discounted Allhat.
Allhat’s proponents discounted the Australian study as less authoritative, and they dismissed the other criticisms.
Still, the arguments “muddied the waters,” said Dr. Randall S. Stafford of Stanford, who studied the effect of Allhat on prescriptions. “The message,” he said, “was no longer as clear to physicians.”
Science Moves On
By the time the Allhat results were released, lisinopril, the ACE inhibitor, had become generic. That meant AstraZeneca and Merck, which sold a version of the compound as Prinivil, had less interest in defending their drugs.
Not so Pfizer. Norvasc was the best-selling hypertension treatment in the world, with sales of $3.8 billion in 2002, and Pfizer’s second-biggest drug behind the cholesterol medication Lipitor.
The company set out to accentuate the positive. In a news release after the Allhat results were announced, it said that Norvasc was found to be “comparable to the diuretic in fatal coronary heart disease, heart attacks and stroke.” And in a medical journal advertisement, it proclaimed “ALL HATs off” to its drug.
Neither the news release nor the ad, however, included the 38 percent greater risk of heart failure with Norvasc in the Allhat study.
Nor did Hank McKinnell, then Pfizer’s chief executive, mention heart failure in lauding the results during his quarterly earnings conference call with analysts a few weeks after the Allhat report was released. “Contrary to what you might have read in the press,” Mr. McKinnell said, “Allhat is extremely positive for Norvasc. It will be our job to explain that to the medical community.”
Dr. Paul K. Whelton, president of Loyola University Health System and the current chairman of the Allhat steering committee, said that Pfizer and other drug companies “took what was in their best interest and ran with those, and conveniently didn’t mention other things.”
Pfizer defends its actions. Dr. Michael Berelowitz, the head of Pfizer’s global medical organization, said that in the trial’s design, heart failure was merely one component of a broader measure of various cardiovascular problems. And in that broader measure, Dr. Berelowitz said, there was no difference between Norvasc and the diuretic. Also, he said, the label for Norvasc already contained a precaution about heart failure.
“Further action regarding the heart failure finding was therefore not considered necessary,” he said in a statement in response to questions.
Pfizer was not the only company promoting its drugs. The drug giant Novartis, for example, was spending heavily to market Diovan, a leader among a class of hypertension drugs called angiotensin receptor blockers, which were too new to have been included in Allhat. Diovan, which had more than $5 billion in sales last year, sells for $1.88 to $3.20 a pill on drugstore.com, compared with 8 to 31 cents for a diuretic.
No company, though, was spending money to promote generic diuretics. So the federal Heart, Lung and Blood Institute recruited Allhat investigators, provided them with training and sent them to proselytize fellow physicians. In all, 147 investigators gave nearly 1,700 talks and reached more than 18,000 doctors and other health care providers.
But it was a coffee-and-doughnuts operation compared with the sumptuous dinners that pharmaceutical companies used to market to doctors. Moreover, the steering committee’s outreach program did not get under way until about three years after the results were published.
Dr. Stafford of Stanford said the outreach seemed to have had a slight effect on increasing the use of diuretics.
The results of Pfizer’s efforts are easier to quantify. Norvasc sales continued to grow to $4.9 billion in 2006, falling only after the drug lost patent protection in the United States in 2007.
Tangles and Strife
Tensions about industry influence reached even the study’s own steering committee. Dr. Furberg, the chairman, bluntly accused some members of the committee of being agents of the industry.
One member, Dr. Richard H. Grimm Jr. of the University of Minnesota, had been receiving tens of thousands of dollars a year from Pfizer since at least 1997, according to reports that pharmaceutical companies file in that state.
In 2003, the year after the Allhat results were published, Dr. Grimm’s payments from Pfizer soared to more than $200,000 — an increase that The New York Times reported in 2007.
Dr. Grimm said in a recent interview that about half those fees in 2003 came from giving about 100 Pfizer-sponsored talks to doctors about Allhat. Dr. Grimm said he gave mainly the standard Allhat-sanctioned talk. But instead of saying diuretics were outright better than the other drugs, he said they were as good or better.
Meanwhile, Dr. Grimm had led an effort to remove Dr. Furberg from his position on the grounds that he had not been impartial.
“He had a vendetta against the calcium channel blockers,” Dr. Grimm said. Dr. Furberg had been publicly questioning the safety of those drugs based on some studies he did in the 1990s. The effort to oust Dr. Furberg failed in 2001. But in August 2004, Dr. Furberg resigned as chairman, contending that there had not been enough effort to disseminate the Allhat message.
Dr. Whelton, who took over as chairman, said that the study’s message was never compromised by industry ties on the steering committee.
“Curt is a wonderful guy who is a crusader,” said Dr. Whelton, who did not have industry ties and was not involved in the effort to unseat Dr. Furberg. “He has certainly rubbed a lot of people, even good friends, the wrong way.”
Changing Practice
Experts see several lessons to be learned from Allhat.
One is that “all trials have flaws” that leave the results open to interpretation, said Dr. Robert M. Califf, a cardiologist at Duke who served on the safety monitoring committee of Allhat.
Another is that providing doctors information is “necessary, but not sufficient” to urge them to change their practices, said Dr. Carolyn M. Clancy, director of the federal Agency for Healthcare Research and Quality, which itself conducts studies comparing different medical treatments.
And while insurers can influence practice through reimbursement policies, they did not seem to have pushed strongly for diuretics after Allhat, in part because some of the other drugs had become generic.
Even the cost-conscious medical system at the Department of Veterans Affairs did not require diuretics, because too many doctors would probably have requested exceptions, said Dr. William C. Cushman, chief of preventive medicine at the department’s medical center in Memphis.
Dr. Cushman, a member of the Allhat steering committee, said diuretic use in the system was still “much lower” than he thought it should be.
Dr. Clancy said that her agency was now mainly using insurance records to judge how treatments perform. While clinical trials are the gold standard, she said, they are costly and time-consuming.
And, she added, “You might be answering a question that by the time you are done, no longer feels quite as relevant.”

Some Breast Cancers May Regress on Their Own

By Amanda Gardner
29 nov 2008- Some breast cancers may naturally disappear without treatment, a study of women undergoing mammography suggests.
The Norwegian study found that more cases of breast cancer were diagnosed after a regular screening program was put in place than before. That has led specialists to suspect that some of the diagnosed tumors would have spontaneously regressed had they not been detected and treated as the result of more rigorous mammography guidelines.
But since doctors can't yet determine which tumors might regress and which might go on to be dangerous, the finding isn't likely to change recommendations for mammography, experts said.
"The problem is, we don't know the natural history [of breast cancer]," said Dr. Jay Brooks, chairman of hematology/oncology at Ochsner Health System in Baton Rouge, La. "I am sure there are some that do regress. The problem is, we can't pick up those that are going to regress. It's one of the unanswerable questions."
The study was published in the Nov. 24 issue of the Archives of Internal Medicine.
Cancer experts have long suspected that some cancers may grow and then, for reasons that are unclear, simply shrink again and disappear. The new breast cancer trial appears to support that notion.
The study took advantage of the fact that new biennial (once every two years) screening mammography programs were instituted throughout Europe in the 1990s. Such a program began in Norway in 1996.
Researchers from the Norwegian Institute of Public Health tracked the incidence of breast cancer among more than 119,000 women aged 50 to 64 who participated in three rounds of biennial mammography screening between 1996 and 2001.
They then compared that data to the rates of breast cancer for almost 110,000 women of similar age between 1992 and 1997, largely before the new guidelines came into effect. When Norway began offering mammograms in 1996, almost all these women went and got a one-time screen.
Although it might be expected that the two groups of women would have breast cancer at similar rates, they did not. In fact, the women in the later cohort -- who got mammograms once every 2 years -- had a 22 percent higher rate of tumors than the women in the earlier, less heavily screened group.
According to the authors, changes in hormone therapy use over the study period did not explain the difference. So why would more frequent screening mean more cancers?
What probably happened, the authors theorized, is that some of the tumors detected during more frequent screening would not otherwise have caused women trouble if they had remained undetected. These tumors might have either remained stable or, more likely, spontaneously regressed.
In fact, there have been 32 cases of spontaneous regression of breast cancer reported in one recent review of the medical literature. And not all actual cases of spontaneous regression end up being documented.
In addition, autopsy studies have revealed that many women die without ever knowing they had a breast cancer.
One expert was intrigued by the findings.
"The study is very provocative and it generates an interesting hypothesis: that it's possible some screen-detected breast cancers would not ever lead to death from breast cancer and are unnecessarily diagnosed and treated," said Dr. Jeanne Mandelblatt, associate director for population sciences at Georgetown University's Lombardi Comprehensive Cancer Center in Washington, D.C.
"But this study design can't prove or disprove that hypothesis," she added. "This study is inconclusive because these women were not randomized; there's no data about the tumor sizes or tumor characteristics in the two groups, and no data about the breast cancer death rate in the two groups."
Still, the finds should impact breast cancer research, experts say. "If the spontaneous remission hypothesis is credible, it should cause a major re-evaluation in the approach to breast cancer research and treatment," wrote Robert Kaplan, of the University of California, Los Angeles, and Dr. Franz Porzsolt of the Clinical Economics University of Ulm, Germany, in an editorial that accompanied the journal article. "Certainly, it is worthy of further evaluation."
Right now, however, doctors cannot tell a "bad" breast tumor from a potentially harmless one, so regular mammography screening is still valuable.
"For women, the take-home message remains that mammography done as recommended does decrease the chance of dying from breast cancer across the general population," Mandelblatt said. "Women need to know that there are risks and benefits to all medical interventions, including screening mammography, and the policy recommending mammography is based on the fact that the benefits outweigh some of these harms."

Study Recruiting From Alzheimer's-Prone Families


29 nov 2008-- The adult children of people with the rarer, inherited form of Alzheimer's disease are being sought for a new study to better understand the biology of the brain disorder.
Three hundred adults with a biological parent diagnosed with a known genetic mutation causing the rare, early-onset form of Alzheimer's are needed for the six-year, $16 million study being funded by the U.S. National Institute on Aging. The Dominantly Inherited Alzheimer's Disease Network (DIAN) study aims to identify the sequence of brain changes that occur even before symptoms begin to appear. By understanding this process, researchers hope to also gain insight into the more common late-onset form of Alzheimer's.
"This collaborative, international effort will link a network of research sites in the United States, England and Australia to family members of people with these rare forms of Alzheimer's," NIA Director Richard J. Hodes said in a news release issued by the group's parent agency. "By sharing data within the network, we hope to advance our knowledge of the brain mechanisms involved in Alzheimer's, eventually leading to targets for therapies that can delay or even prevent progress of the disease."
Most Alzheimer's patients have the late-onset form of the disease, in which memory loss and other symptoms appear at age 60 or older. Only five percent have the inherited form of the disease, which takes hold in people as young as 30.
Study participant will undergo similar assessments, including genetic analysis and cognitive testing. Using that information, researchers will build a shared database of blood and cerebral spinal fluid samples and neuroimages, such as MRI and PET amyloid images.
"While three mutated genes -- amyloid precursor protein (APP), presenilin 1 and presenilin 2 -- are known causes of inherited early-onset Alzheimer's, DIAN researchers now hope to find the biomarkers, or indicators, that herald the disease at its earliest stages," NIA Division of Neuroscience Director Marcelle Morrison-Bogorad said in the news release. "By closely monitoring the biomarkers of the DIAN volunteers, both those with and those without the mutated genes, we should gain insight into the underlying pathology behind both early- and late-onset forms of the disease."
People interested in participating in the DIAN study should visit www.dian-info.org. Study participants must be aged 18 or older.
More information
The U.S. National Institute on Aging has more about Alzheimer's disease.

Transfusing Anemic Cancer Patients Boosts Clot Risk


29 nov 2008 -- Giving blood transfusions to treat anemia in cancer patients increases the risk of potentially lethal blood clots, say University of Rochester, N.Y., researchers.
But this risk is no greater than other treatments for cancer treatment-related anemia, the scientists said, after having analyzed data on more than 70,500 cancer patients who received transfusions at 60 medical centers from 1995 to 2003.
Of those patients, 7.2 percent developed venous thromboembolism (VTE), and 5.2 percent developed arterial thromboembolism (ATE), compared with rates of 3.8 percent and 3.1 percent, respectively, among patients who didn't receive transfusions.
The study was published in the latest issue of the journal Archives of Internal Medicine.
Anemia is a common side effect of chemotherapy. Red blood cell-boosting drugs called erythropoiesis-stimulating agents (ESAs) are used to fight anemia, but these medications increase the risk of blood clots, and the U.S. Food and Drug Administration last year issued restrictions on their use. It was hoped that red blood cell transfusions would offer a safe alternative.
While blood transfusion did increase the risk of blood clots, the risk is comparable to that of ESAs.
The researchers said their findings pose a dilemma for doctors who want to prevent blood clots, one of the leading causes of illness and death in cancer patients. Parts of blood clots can break off and travel to other parts of the body, causing a serious problem in the lungs (pulmonary embolism) or a heart attack or stroke.
"We've known that medications used for the treatment of anemia in cancer cause blood clots, and using transfusions was an alternative that some doctors chose to try to avoid this problem, lead author Dr. Alok Khorana said in a university news release "This study shows that transfusions may be no better for patients. We need to be cautious in the use of transfusions and search for ways to reduce our patients' risk of developing blood clots, which are dangerous."
"We need to understand why people who get transfusions are more likely to get blood clots," Dr. Charles Francis, professor of medicine and director of the hemostasis and thrombosis program, said in the news release.

Selenium may slow march of AIDS

29 nov 2008--Increasing the production of naturally occurring proteins that contain selenium in human blood cells slows down multiplication of the AIDS virus, according to biochemists.
"We have found that increasing the expression of proteins that contain selenium negatively affects the replication of HIV," said K. Sandeep Prabhu, Penn State assistant professor of immunology and molecular toxicology. "Our results suggest a reduction in viral replication by at least 10-fold."
Selenium is a micronutrient that the body needs to maintain normal metabolism. Unlike other nutrients, which bind to certain proteins and modulate the protein's activity, selenium gets incorporated into proteins in the form of an amino acid called selenocysteine.
These proteins – selenoproteins – are especially important in reducing the stress caused by an infection, thereby slowing its spread.
Upon infecting a person, the virus quickly degrades selenoproteins so that it can replicate efficiently. It is unclear just how the virus is able to silence these proteins but Prabhu and his colleagues believe that stress inflicted on cells by the rapidly dividing virus, which produces a key protein known as Tat, is the likely culprit.
Tat is one of about 14 odd proteins produced by HIV during the first stage of infection. The job of these proteins is to trigger the expression of all the other genes that the virus needs to sustain itself. In addition, Tat also plays a key role in helping the virus replicate.
One of the proteins that targets Tat is a selenoprotein known as TR1.
"Since HIV targets the selenoproteins, we thought that the logical way to deal with the virus is to increase the expression of such proteins in the body," explained Prabhu, whose team's findings are outlined this week (Nov. 28) in the Journal of Biological Chemistry.
Researchers first isolated blood cells from healthy human volunteers who did not have HIV, and infected those cells with the virus. Next, they added tiny amounts of a selenium compound – sodium selenite – into the cell culture to see the effect on viral replication.
Results from the tests indicate that the addition of selenium inhibits the replication of HIV at least 10-fold, compared to cell cultures in which no selenium is added. When the researchers selectively reduced production of the selenium containing TR1 protein, they observed a 3.5-fold increase in viral replication.
"This confirms that while increasing the expression of TR1 has a negative impact on the replication of HIV, reducing it helps the virus replicate more efficiently," explained Prabhu. He believes that TR1 works by upsetting the chemical structure of Tat, which in turn reduces the virus' ability to replicate.
"Once we fully understand the function of these selenium proteins, it will give us a handle to come up with more effective drugs," said Prabhu, whose work is partly funded by the National Institutes of Health.

Vitamin K linked to insulin resistance in older men

BOSTON, 28 nov 2008 - Vitamin K slowed the development of insulin resistance in elderly men in a study of 355 non-diabetic men and women ages 60 to 80 who completed a three-year clinical trial at the Jean Mayer Human Nutrition Research Center on Aging at Tufts University (USDA HNRCA).
"Men who received vitamin K supplementation had less progression in their insulin resistance by the end of the clinical trial," said Sarah Booth, senior author and director of the Vitamin K Laboratory at the USDA HNRCA. "Conversely, we saw progression in insulin resistance in women who received vitamin K supplementation, and in the men or women who were not given vitamin K supplements."
Among those given vitamin K, both men and women took daily multivitamins containing 500 micrograms of vitamin K, five times the Adequate Intake (AI) recommended by the Institute of Medicine's Food and Nutrition Board, with instructions to maintain normal diets without any additional supplementation. They also received a calcium and vitamin D supplement. Men and women in the control group received no vitamin K supplementation but did receive the multivitamin and the calcium and vitamin D supplement. For the present study, insulin resistance was assessed by the homeostasis model (HOMA-IR). Additionally, participants' blood glucose and blood insulin levels were measured following a minimum 10-hour fast. In addition to improved insulin resistance, the supplemented men had lower blood insulin levels compared to the unsupplemented men at the conclusion of the study.
Insulin is a hormone which plays a role in transporting sugar into cells so it can be converted into energy. A pre-cursor to diabetes, insulin resistance occurs when the body cannot use insulin properly, causing glucose to build up in the blood. People who are obese or overweight are prone to insulin resistance because excess fat can interfere with insulin function.
Writing in the November issue of Diabetes Care, the authors speculate that weight might explain why only the vitamin K supplemented men improved their insulin resistance. "In our study, there was a higher prevalence of obese or overweight women in the vitamin K supplementation group compared to the male supplementation group," Booth said. "Vitamin K is stored in fat tissue. If there is excess fat, vitamin K may not be readily available to cells that require it to process glucose."
Because there are few studies of vitamin K and insulin resistance, the authors encourage further investigation of their findings and alternative study designs. "The original purpose of the present study was to assess the effect of vitamin K1, or phylloquinone, supplementation on changes in bone mineral density and vascular calcification," Booth said. "For instance, there is a way to achieve a more direct measure of insulin secretion than HOMA-IR. Also, our study is limited to caucasian adults. We acknowledge our findings may not apply to the general population."
Although vitamin K supplements were used for the study, the authors say the study dosage is attainable by consuming a healthy diet. Foods considered good sources of vitamin K include brussels sprouts, broccoli, and dark, leafy greens, such as spinach and collards.

Brain scans show root of memory glitch with aging

By MALCOLM RITTER
NEW YORK, 28nov 2008 – Brain scans of older people in a noisy lab machine give biological backing to the idea that distraction hampers memory with aging, researchers reported Wednesday.
The finding bolsters a theory about one reason why memory weakens with age: older people have more trouble remembering some things because they're more easily distracted when they try to learn them.
The memory exercise reported in the latest issue of the Journal of Neuroscience dealt with recognizing faces, but the findings apply to the more general task of trying to remember something a person sees or hears, said lead author Dale Stevens.
Stevens, a postdoctoral researcher at Harvard University, did the work while at the Rotman Research Institute at Baycrest, which is affiliated with the University of Toronto.
Older people who have to learn something should do all they can to focus on that task and eliminate potential distractions, he advised.
The study compared 10 healthy people in their 60s and 70s to a dozen younger volunteers, ages 22 to 36. Their brains were scanned while they looked at photographs of people they did not know. As each photograph was displayed for one second, the volunteers were asked if they'd seen it before in the study.
In all they saw 180 different faces, of which 120 showed up a second time. The older participants failed to recognize a face they'd already seen 43 percent of the time, compared to 26 percent for the younger volunteers.
Researchers went back to see what was going on in the brains of the volunteers when they first saw a face that they later failed to recognize. Why didn't those faces get planted in memory?
In both groups, a brain area called the hippocampus, which is involved in memory, was less active when a face failed to stick in the memory than when it did. That was no surprise. More interestingly, the older group also showed heightened activity in certain other brain areas while the younger volunteers did not.
Those areas included the auditory cortex, which plays a role in analyzing sound, and several areas involved in directing attention, Stevens said.
So what was going on? The brain-scanning machine was noisy, with lots of knocking, buzzing and banging like a jackhammer, Stevens said. Even with the earplugs the volunteers wore, "it's a little distracting," he said.
The brain activity in the older volunteers shows that the noise was more distracting to them than to the younger participants, and reveals the brain circuits involved, researchers concluded.
The study could not address when a person's brain starts to act up this way. But Cheryl Grady of the Rotman institute, another author, said she suspects it may begin between ages 40 and 60.
Dr. Barry Gordon, a neurology professor and memory expert at The Johns Hopkins Medical Institutions in Baltimore, called the work "an appreciable advance." A next step could be seeing whether older people will do better on a memory test if they're warned about the distraction problem, said Gordon, who wasn't involved in the new study.
In any case, he said, "if you want to remember something, it's more important if you're older than younger not to be listening to your iPod."
___
On the Net:
The Journal of Neuroscience: http://www.jneurosci.org/

Women Smokers Lose 14.5 Years Off Life Span

28 nov 2008-- During Lung Cancer Awareness Month in November, female smokers should take advantage of available resources, pick a quit day, and start taking steps toward kicking the habit, urges The American College of Obstetricians and Gynecologists (ACOG).
Even though smoking takes an average of 14.5 years off women's lives, almost one in five American women age 18 and older smokes.
"The damaging effects of smoking on women are extensive, well-documented, and can be observed from the cradle to the premature grave," Dr. Sharon Phelan said in an organization news release. She helped develop ACOG's smoking cessation materials for health care providers.
"Smoking is a harmful habit that negatively affects nearly every organ in the body. There's just no good reason not to quit," she said.
Here's a list of the dangers:
Smoking is the main cause of lung cancer, the leading cause of cancer death in women. Since 1950, lung cancer deaths among women have increased more than 600 percent, according to ACOG.
Smoking also significantly increases the risk of many other cancers in women, including breast, oral, pharynx, larynx, esophageal, pancreatic, kidney, bladder, uterine, and cervical cancers.
Women who smoke are twice as likely to develop coronary heart disease and 10 times more likely to die from chronic obstructive pulmonary disease (COPD) than nonsmokers.
Smoking increases the risk of emphysema, bronchitis, osteoporosis, rheumatoid arthritis, cataracts, lower bone density after menopause, and hip fracture. It can also contribute to early menopause, gum disease, tooth loss, and premature skin aging.
Reproductive-age women who smoke may have trouble conceiving, and pregnant women who smoke are at high risk of delivering preterm or low birth weight infants or having babies with poor lung function, bronchitis or asthma.
Women over age 35 who smoke and take birth control pills are at risk for developing deadly blood clots.
"Pregnant women should absolutely not smoke, and smoking should not be allowed in the home after a baby is born," Phelan said. "Unfortunately, we know that infants and young children are more heavily exposed to secondhand smoke than adults, and parents, guardians, or other members of the household often smoke around them."
Almost 60 percent of children ages 3 to 11 are exposed to secondhand smoke, which puts them at increased risk for a wide range of health problems.

Bone Finding May Point to Hope for Osteoporosis

By GINA KOLATA
28 nov 2008--Bone formation appears to be controlled by serotonin, a chemical previously known mainly for its entirely separate role in the brain, researchers are reporting.
The discovery could have enormous implications, osteoporosis experts say, because there is an urgent need for osteoporosis treatments that actually build bone.
Osteoporosis affects 10 million Americans over age 50. It results in bone loss, and its hallmark is fragile bones that break easily. With one exception, current treatments only slow further bone loss rather than increase bone formation. And the exception, parathyroid hormone, given by injection, is recommended only for short-term use and costs about $6,700 a year.
But in a paper published online Wednesday in the journal Cell, a team led by Dr. Gerard Karsenty, chairman of the department of genetics and development at the Columbia University College of Physicians and Surgeons, reports the discovery of an unexpected system that appears to control bone formation.
At its heart is serotonin made by the gut rather than the brain, whose role outside the brain had been a mystery. Ninety-five percent of the body’s serotonin is made by the gut, but gut serotonin cannot enter the brain because it is barred by a membrane, the so-called blood-brain barrier.
Dr. Karsenty reports, though, that gut serotonin can directly control bone formation. It is released into the blood, and the more serotonin that reaches bone, the more bone is lost. Conversely, the less serotonin, the denser and stronger bones become. Dr. Karsenty was even able to prevent menopause-induced osteoporosis in mice by slowing serotonin production.
Osteoporosis researchers were dumbfounded by the report.
“I am very excited by this paper,” said Dr. J. Christopher Gallagher, an osteoporosis specialist and professor of medicine at Creighton University. “It is a groundbreaking paper. One is completely surprised.”
Dr. Ronald N. Margolis, senior adviser for molecular endocrinology at the National Institute of Diabetes and Digestive and Kidney Diseases, said: “I was astonished. My jaw was dropping.”
Dr. Clifford J. Rosen, a senior scientist at the Maine Medical Center Research Institute, was no less impressed. “This is amazing science,” Dr. Rosen said. “Amazing. The science is spectacular.”
Dr. Ethel S. Siris, who directs the Toni Stabile Osteoporosis Center at Columbia, cautioned that the work was not with humans but instead involved mice that were engineered to have human genes. “This stuff is really exciting basic — underscore basic — research,” Dr. Siris said.
The story of the serotonin-bone connection began with reports of a rare inherited condition causing fragile bones and blindness. Children with the condition had bones so weak that they needed wheelchairs or devices to assist them in walking.
The problem turned out to be a mutation that inactivated a gene called LRP5.
A few years later, another mutation was found in LRP5 that produced the opposite effect: extremely dense bones and resistance to osteoporosis. In this case, LRP5 was overactive. People with this gene mutation, Dr. Karsenty said, had jawbones so dense that it was difficult to extract their teeth.
Osteoporosis researchers jumped on those findings, realizing that LRP5 could hold clues to the disease. But most assumed that LRP5’s role was in bone itself.
With Dr. Karsenty’s work, said Dr. Bjorn R. Olsen, a bone growth researcher at Harvard Medical School, “that has now been proven completely wrong.”
Instead, Dr. Karsenty discovered that LRP5 acts on serotonin-producing cells in the gut. It blocks an enzyme that converts the amino acid tryptophan to serotonin. The more LRP5, the more the enzyme is blocked, and the less serotonin is made. The gene has no effect, apparently, on brain cells that make serotonin.
After the gut releases serotonin into blood, serotonin travels to bone-forming cells and inhibits their growth.
“We made mice with the inactivated gene,” Dr. Karsenty said, in which “the bone-forming cells are on strike.” The cells simply would not grow, and the mice developed severe osteoporosis.
But the bone cells themselves were fine. When Dr. Karsenty grew them in the lab, where they were not exposed to serotonin, they developed normally.
That told him that the problem was not in the bone cells but in some molecule in the mice’s circulation. And that, Dr. Karsenty says, led him to serotonin. The mice had four to five times more serotonin in their blood than mice without the mutation.
He tested the idea by adding serotonin to normal mouse bone cells in the laboratory. The cells stopped growing.
He could even control bone formation in the mice with the mutated gene by giving them a diet deficient in tryptophan, the precursor of serotonin. Without much tryptophan, the mice could not make much serotonin. And their bones grew denser. (But animals with a normal version of the gene did not grow denser bones when they ate a tryptophan-deficient diet.)
Dr. Karsenty and his colleagues also did the reverse experiment, making mice with the mutation that causes superdense bones in humans. Those animals, he said, had “amazing bones” that were hard to break, and they did not develop osteoporosis.
When Dr. Karsenty looked at patients with the dense-bones mutation, they had low levels of serotonin in their blood.
Osteoporosis patients, though, tend to have normal serotonin levels, Dr. Karsenty said. Their disease involves not impaired bone formation but accelerated bone loss.
Bone is constantly being formed and absorbed, but when the balance shifts toward loss more than formation, the result can be osteoporosis. Dr. Karsenty’s hope is to find a drug that depresses the gut’s serotonin synthesis and stimulates bone growth in these patients.
Dr. T. John Martin, an emeritus professor of medicine at the University of Melbourne in Australia, cautions that all this will take years. He is enthusiastic, though.
“This will really change thinking in the field,” Dr. Martin said. “It will have a big impact. I’m certain of that.”

Nitric oxide can alter brain function

Finding has implications for the treatment of neurodegenerative disease and dementia

28 nov 2008--Research from the Medical Research Council (MRC) Toxicology Unit at the University of Leicester shows that nitric oxide (NO) can change the computational ability of the brain. This finding has implications for the treatment of neurodegenerative diseases such as Alzheimer's Disease and our understanding of brain function more generally.
The research is led by Professor Ian Forsythe and is reported in the journal Neuron on 26th November.
Professor Forsythe, of the MRC Toxicology Unit, explains: "It is well known that nerve cells communicate via the synapse – the site at which chemical messengers (neurotransmitters such as acetylcholine or glutamate) are packaged and then released under tight control to influence their neighbours.
"Nitric oxide is a chemical messenger which cannot be stored and can rapidly diffuse across cell membranes to act at remote sites (in contrast to conventional neurotransmitters which cannot pass across cell membranes).
"It is broadly localized in the central nervous system, where it influences synaptic transmission and contributes to learning and memory mechanisms. However, because it is normally released in such minute quantities and is so labile, it is very difficult to study.
"We have exploited an in vitro preparation of a giant synapse -called the calyx of Held, developed here at the University of Leicester in the 1990s- and its target in the auditory pathway to explore nitric oxide signalling in the brain.
"We show that NO is made in response to incoming synaptic activity (activity generated by sound received by the ear) and that it acts to suppress a key potassium ion-channel (Kv3). Normally these ion-channels keep electrical potentials very short-lived, but nitric oxide shifts their activity, slowing the electrical potentials and reducing information passage along the pathway, acting as a form of gain control.
"Surprisingly, the whole population of neurons were affected, even those neurons which had no active synaptic inputs, so indicating that nitric oxide is a 'volume transmitter' passing information between cells without the need for a synapse. Such a function is ideal for tuning neuronal populations to global activity. On the other hand, too much nitric oxide is extremely toxic and will cause death of nerve cells; so within the kernel of this important signaling mechanism are the potential seeds for neurodegeneration, which if left unchecked contribute to the pathologies of stroke and dementias."
In the future Professor Forsythe's research group will be trying to understand how these signalling mechanisms are applicable elsewhere in the brain and will investigate how aberrant signalling contributes to neurodegenerative disease processes such as in Alzheimer's disease..

Scientists Find Clues to Aging in a Red Wine Ingredient’s Role in Activating a Protein

By NICHOLAS WADE
27 nov 2008--A new insight into the reason for aging has been gained by scientists trying to understand how resveratrol, a minor ingredient of red wine, improves the health and lifespan of laboratory mice. They believe that the integrity of chromosomes is compromised as people age, and that resveratrol works by activating a protein known as sirtuin that restores the chromosomes to health.
The finding, published online Wednesday in the journal Cell, is from a group led by David Sinclair of the Harvard Medical School. It is part of a growing effort by biologists to understand the sirtuins and other powerful agents that control the settings on the living cell’s metabolism, like its handling of fats and response to insulin.
Researchers are just beginning to figure out how these agents work and how to manipulate them, hoping that they can develop drugs to enhance resistance to disease and to retard aging.
Sirtris, a company Dr. Sinclair helped found, has developed a number of chemicals that mimic resveratrol and are potentially more suitable as drugs since they activate sirtuin at much lower doses than resveratrol. This month, one of these chemicals was reported in the journal Cell Metabolism to protect mice on fatty diets from getting obese and to enhance their endurance in treadmills, just as resveratrol does.
Though the sirtuin field holds considerable promise, the dust has far from settled. Resveratrol is a powerful agent with many different effects, only some of which are exerted through sirtuin. So drugs that activate sirtuin may not be as splendid a tonic for people as resveratrol certainly seems to be for mice.
The new finding concerns maintenance of the chromosomes, the giant molecules of DNA that make up the genome.
Each cell has six feet of DNA packed into its nucleus, carrying the 20,000 or so genetic instructions needed to operate the human body. Each cell must provide instant access to the handful of these genes needed by its cell type, but also keep the rest firmly switched off to avoid chaos.
Sirtuin’s normal role is to help gag all the genes that a cell needs to keep suppressed. It does so by keeping the chromatin, the stuff that wraps around the DNA, packed so tightly that the cell cannot get access to the underlying genes.
But sirtuin has another critical role, one that is triggered by emergencies like a break in both DNA strands of a chromosome. After a double strand break, sirtuin rushes to the site to help knit the two parts of the chromosome back together. But in this salvage operation, it leaves its post, and the genes it was repressing are liable to come back into action, causing mayhem.
This, Dr. Sinclair and his colleagues suggest, may be a fundamental cause of aging in mice and probably people, too.
The gene-gagging role of sirtuin was discovered in the 1980s by biologists studying yeast, a standard laboratory organism. Dr. Sinclair and Leonard Guarente of the Massachusetts Institute of Technology found in 1997 that sirtuin could also repair a certain kind of genomic damage in yeast, and in doing so extended the yeast cell’s lifespan. But this particular kind of damage does not occur in mammalian cells, raising the puzzle of why extra sirtuin should be good for them.
Dr. Sinclair’s new report, if verified, resolves this problem by showing that sirtuin has retained its genomic repair role in higher organisms but that the repair is focused on a different kind of genomic damage — that of breaks in a chromosome.
These experiments “elegantly demonstrate” that sirtuin works in much the same way in mammals as in yeast, Dr. Jan Vijg of the Albert Einstein College of Medicine wrote in a commentary in Cell. The question now is whether sirtuin is a pro-longevity factor in mammals, he said in an e-mail message.
Ronald Evans, a biologist at the Salk Institute, said the new report was provocative but did not prove the case that the relocation of sirtuin was a cause of aging. Tests with mice genetically engineered to lack the sirtuin gene could show if the mice suffered from premature aging, as Dr. Sinclair’s idea would predict.
Dr. Sinclair said he agreed that the case for sirtuin’s role in aging had not been proved. “We are careful not to say this is the cause of aging, but based on everything we know it’s not a bad hypothesis,” he said.
It would be nice to test aging in mice that lack the sirtuin gene, as Dr. Evans proposed, but they die too young, Dr. Sinclair said.
Dr. Sinclair has been taking large daily doses of resveratrol since he and others discovered five years ago that it activated sirtuin. “I’m still taking it, and I feel great,” he said, “but it’s too early to say if I’m young for my age.”

Estrogen therapy could be dangerous for women with existing heart risk

ANN ARBOR, Mich., 27 nov 2008---Hormone therapy could accentuate certain pre-existing heart disease risk factors and a heart health evaluation should become the norm when considering estrogen replacement, new research suggests.
The research also showed that in women without existing atherosclerosis, hormone therapy use included some positive effects on lipids but also some negative effects related to heart health, said MaryFran Sowers, lead researcher and professor of epidemiology at the University of Michigan School of Public Health.
The U-M study came about, Sowers said, in trying to explain what's behind the so-called timing hypothesis. The timing hypothesis suggests that if a woman implements a hormone therapy program within six years of her final menstrual period, this narrow window is enough to deter heart disease from developing with the onset of menopause. But the U-M findings suggest that explanation isn't quite so simple, Sowers said.
Even within the six-year window, there were negative aspects related to heart disease. While the positive outcomes on HDL and LDL cholesterol levels were observed, Sowers said, researchers also saw negative outcomes in terms of the inflammation process---which can be related to heart disease.
Sowers said the research shows it's critical for women considering hormone therapy to discuss their heart health with their doctor.
"If the woman walks into the doctor's office with a certain degree of (heart disease) burden already, then she and her health care provider may decide that hormone therapy adds too much to the burden," Sowers said. "If she doesn't have that burden, they may decide that hormone therapy is an acceptable burden.
"The woman should say to her health care provider, 'What kind of information do we need to gather in order to make an informed decision about whether or not hormone therapy should be pursued,'" Sowers said. '"I understand there could be some heart disease risk, but that the risk may be based upon where I am now, and can you tell me where that is?'"
Heart disease risk can be measured through lipid panels, which are standard, but also by measuring inflammation markers, Sowers said. Tests for inflammation markers exist but their measurement isn't standard when a women is considering hormone therapy, Sowers said.
Hormone therapy has been controversial for years, and there was a time when there was an almost knee jerk reaction against it, Sowers said. This backlash occurred after the findings from the Women's Health Initiative study showed that some women on estrogen therapy had increased heart disease risk. The six-year timing hypothesis was an attempt to explain the findings in the WHI study, Sowers said.

In sickness and health: Caring for ailing spouse may prolong your life

ANN ARBOR, Mich., 27nov 2008---Older people who spent at least 14 hours a week taking care of a disabled spouse lived longer than others. That is the unexpected finding of a University of Michigan study forthcoming in Psychological Science, a journal of the Association for Psychological Science.
The study supports earlier research showing that in terms of health and longevity, it really is better to give than to receive.
"These findings suggest that caregivers may actually benefit from providing care under some circumstances," said U-M researcher Stephanie Brown, lead author of the study report. "Previous studies have documented negative health effects of caregiving. But the current results show that it is time to disentangle the presumed stress of providing help from the stress of witnessing a loved one suffer."
Brown is an assistant professor of internal medicine at the U-M Medical School and a faculty associate at the U-M Institute for Social Research (ISR). She is also affiliated with the Ann Arbor Veterans Affairs Hospital.
For the study, Brown and colleagues reviewed seven years of data from the U-M Health and Retirement Study, a nationally representative sample of Americans age 70 and older. The analysis focused on 1,688 couples, all of whom lived on their own.
At the start of the study in 1993, both members of each couple reported how much help they received from their spouse with a long list of everyday activities. These included eating, dressing and bathing, preparing meals, managing money and taking medications.
The vast majority---approximately 81 percent---said they received no help at all from their spouse. Another nine percent reported getting less than 14 hours of help a week, and the remaining ten percent reported getting 14 hours of help or more each week.
Over the course of the study, 909 people died---about 27 percent of the study population. After controlling for health, age, race, gender, education, employment status and net worth, Brown and colleagues found that the individuals who provided at least 14 hours of care a week to their spouses were significantly less likely to have died during the study period than those who provided no spousal care.
The results of this study add to a growing literature on the positive, beneficial health effects of caregiving, helping and altruism, according to Brown. Her own earlier work has shown that providing social support to friends, relatives and neighbors has a beneficial impact on mortality and on coping with spousal loss.
Brown has a theory about why this is the case. Rather than assuming that humans are selfish and necessarily act only on the basis of rational self-interest, she believes that strong evolutionary forces favor altruistic motivation when individuals are interdependent.
"There is growing recognition that economic decisions may be influenced by complex motivations, not limited to self-interest," she said. "We don't know yet exactly how caregiving motivation and behavior might influence health, but it could be that helping another person---especially someone you love---relieves some of the harmful stress effects of seeing that person suffer."
With support from the National Science Foundation, Brown will examine how altruistic, helpful behavior, including caregiving, enhances well-being. Starting in 2009, this research will focus on the neuro-affective mechanisms of helping behavior.
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The ISR Health and Retirement Study is funded by the National Institute on Aging.

Do you know you're having a stroke?

Symptom awareness can improve recovery

ROCHESTER, Minn., 27 nov 2008 -- A Mayo Clinic study shows a majority of stroke patients don't think they're having a stroke -- and as a result -- delay seeking treatment until their condition worsens. The findings appear in the current issue of Emergency Medicine Journal at http://emj.bmj.com/.
Researchers studied 400 patients who were diagnosed at Mayo Clinic's emergency department with either acute ischemic stroke or a transient ischemic attack (TIA), a temporary interruption of blood flow to part of the brain.
Less than half of the patients -- 42 percent -- thought they were having a stroke. In fact, most in the study did not go to the emergency room when symptoms appeared. The median time from onset of symptoms to arrival at the hospital was over three and a half hours. Most said they thought the symptoms would simply go away. The delay in seeking medical help was the same among men and women.
When asked how they knew about stroke symptoms, nearly one-fifth said they thought a stroke always came on gradually. Just over half (51.9 percent) said they thought that seeking medical care immediately was important.
Significance of the findings
"Time is crucial in treating stroke," says Latha Stead, M.D., emergency medicine specialist and lead author of the study. "Each individual's medical background differs and affects recovery, but in general the sooner a patient experiencing a stroke reaches emergency care, the more likely the stroke can be limited and the condition managed to prevent further damage and improve recovery." The researchers say their findings clearly indicate that better public understanding of stroke symptoms will lead to a faster response and better outcomes.
What you should know
Strokes can happen quickly or can occur over several hours, with the condition continually worsening. The thrombus or clot that is causing the stroke can frequently be dissolved or disintegrated so blood can again flow to the brain. In such cases, immediate treatment can mean the difference between a slight injury and a major disability. Interestingly only 20.8 percent of the participants knew about such treatment. By use of stents, medications and other technology, physicians can stop a stroke from spreading and greatly limit damage. Stroke symptoms include:
Sudden numbness, weakness, or paralysis of your face, arm or leg -- usually on one side of the body
Sudden difficulty speaking or understanding speech (aphasia)
Sudden blurred, double or decreased vision
Sudden dizziness, loss of balance or loss of coordination
A sudden, severe "bolt out of the blue" headache or an unusual headache, which may be accompanied by a stiff neck, facial pain, pain between your eyes, vomiting or altered consciousness
Confusion or problems with memory, spatial orientation or perception
In such cases, a stroke gives no warning. But one possible sign of an impending stroke is a TIA. The signs and symptoms of TIA are the same as for a stroke, but they last for a shorter period -- several minutes to a few hours -- and then disappear, without leaving apparent permanent effects. You may have more than one TIA, and the signs and symptoms may be similar or different. A TIA indicates a serious risk that a full-blown stroke may follow.
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Other Mayo researchers involved in the study were Lekshmi Vaidyanathan, M.B.B.S.; Maria Bellolio, M.D.; Rahul Kashyap, M.B.B.S.; Anjali Bhagra, M.B.B.S.; Rachel Gilmore, M.B.B.Ch.; Wyatt Decker, M.D.; Sailaja Enduri, M.B.B.S.; Shaily Mishra, Ph.D.; Helen Wood, R.N.; Ayman Yassa, M.D.; Ann Hoff, M.D.; and Robert Brown, M.D. Dr. Stead is supported by the Mayo Emergency Medicine Research Career Development Award and Mayo Clinic.

New research helps explain genetics of Parkinson's disease

27 nov 2008--A new study by Narendra et al. suggests that Parkin, the product of the Parkinson's disease-related gene Park2, prompts neuronal survival by clearing the cell of its damaged mitochondria.
"[This is] an exciting new discovery that links the fields of mitochondrial quality control and the genetics of Parkinson's disease (PD)," writes Heidi McBride of the University of Ottawa Heart Institute. "…This work significantly increases our understanding of PD and provides a new framework for the development of therapeutic interventions."
The study, as well as McBride's commentary, will appear in the December 1, 2008 print issue of the Journal of Cell Biology (JCB). Both articles will be published online Monday, November 24 (www.jcb.org).
Loss-of-function mutations in the gene Park2, which encodes an E3 ubiquitin ligase (Parkin), are implicated in half the cases of recessive familial early-onset Parkinson's disease. Several lines of evidence suggest that Parkin loss is associated with mitochondrial dysfunction, but exactly how was unknown. To learn more about Parkin's role in cells, Narendra et al. examined the protein's subcellular location. They found that Parkin was present in the cytoplasm of most cells, but translocated to mitochondria in cells that had undergone mitochondrial damage such as membrane depolarization.
Damaged mitochondria can trigger cell death pathways; indeed, dysregulation of mitochondrial health was already thought to be a possible cause of the neuronal cell death associated with Parkinson's disease. The relocation of Parkin to damaged mitochondria, the team showed, sends these defunct organelles to autophagosomes for degradation. Parkin may thus prevent the damaged mitochondria from triggering cell death. Because neurons are not readily replicable, disposing of damaged mitochondria may be especially important in the adult brain.

Microsoft Examines Causes of ‘Cyberchondria’

By JOHN MARKOFF
26 nov 2008--If that headache plaguing you this morning led you first to a Web search and then to the conclusion that you must have a brain tumor, you may instead be suffering from cyberchondria.
On Monday, Microsoft researchers published the results of a study of health-related Web searches on popular search engines as well as a survey of the company’s employees.
The study suggests that self-diagnosis by search engine frequently leads Web searchers to conclude the worst about what ails them.
The researchers said they had undertaken the study as part of an effort to add features to Microsoft’s search service that could make it more of an adviser and less of a blind information retrieval tool.
Although the term “cyberchondria” emerged in 2000 to refer to the practice of leaping to dire conclusions while researching health matters online, the Microsoft study is the first systematic look at the anxieties of people doing searches related to health care, Eric Horvitz said.
Mr. Horvitz, an artificial intelligence researcher at Microsoft Research, said many people treated search engines as if they could answer questions like a human expert.
“People tend to look at just the first couple results,” Mr. Horvitz said. “If they find ‘brain tumor’ or ‘A.L.S.,’ that’s their launching point.”
Mr. Horvitz is a computer scientist and has a medical degree, and his fellow investigator, Ryen W. White, is a specialist in information retrieval technology.
They found that Web searches for things like headache and chest pain were just as likely or more likely to lead people to pages describing serious conditions as benign ones, even though the serious illnesses are much more rare.
For example, there were just as many results that linked headaches with brain tumors as with caffeine withdrawal, although the chance of having a brain tumor is infinitesimally small.
The researchers said they had not intended their work to send the message that people should ignore symptoms. But their examination of search records indicated that researching particular symptoms often led quickly to anxiousness.
They found that roughly 2 percent of all Web queries were health-related, and about 250,000 users, or about a quarter of the sample, engaged in a least one medical search during the study.
About a third of the subjects “escalated” their follow-up searches to explore serious illnesses, the researchers said.
Of the more than 500 Microsoft employees who answered a survey on their medical search habits, more than half said that online medical queries related to a serious illness had interrupted their day-to-day activities at least once.
Mr. Horvitz said that in addition to his interest in creating a Web search tool that would give more reliable answers, the research was driven by clear memories from his medical school education of what was often referred to as “second-year syndrome” or “medical schoolitis.”
He said he remembered “sitting on a cold seat with my legs dangling off the examination table,” convinced that he was suffering from a rare and incurable skin disease.
While the doctor was out of the room, Mr. Horvitz said, he took a look at his medical chart and saw that the doctor’s notes read, “Eric is in medical school, and he has been reading a lot.”
The researchers said that Web searchers’ propensity to jump to awful conclusions was basic human behavior that has been noted by research scientists for decades.
In 1974, the psychologists Amos Tversky and Daniel Kahneman wrote a seminal paper about decisions that are based on beliefs about the likelihood of uncertain events, like the outcome of an election or the future value of the dollar.
They said that people usually employ common sense rules to aid in decisions. The rules can be quite useful, but they also frequently lead to systematic errors in judgment.
The Microsoft researchers noted that reliance on the rankings of Web search results contributes a similar bias to the judgments people make about illness.
At the same time, Mr. Horvitz said he believed that the Web would evolve to offer more reliable information.
In the 1990s, Microsoft researchers built a health advisory system for pregnancy and child care. Mr. Horvitz said that in the future it would be possible to create search engines that were able to detect medical queries and offer advice that did not automatically make Web searchers fear the worst.

New Suspect in Sports Doping Is, No Joke, Viagra

By JERÉ LONGMAN
SCRANTON, Pa., 26 nov 2008 — When George Downey volunteered along with other lacrosse players at Marywood University to take Viagra for a study, he received a snickering nickname from his high school coach. His parents jokingly told their friends. Inquiring minds sent messages to his Facebook page.
“They’re making fun of me,” Mr. Downey, 19, said good-naturedly. “Deep down, I think they’re looking for tips.”
Except that the Marywood study does not involve the bedroom, but the playing field. It is being financed by the World Anti-Doping Agency, which is investigating whether the diamond-shaped blue pills create an unfair competitive advantage in dilating an athlete’s blood vessels and unduly increasing oxygen-carrying capacity. If so, the agency will consider banning the drug.
Viagra, or sildenafil citrate, was devised to treat pulmonary hypertension, or high blood pressure in arteries of the lungs. The drug works by suppressing an enzyme that controls blood flow, allowing the vessels to relax and widen. The same mechanism facilitates blood flow into the penis of impotent men. In the case of athletes, increased cardiac output and more efficient transport of oxygenated fuel to the muscles can enhance endurance.
“Basically, it allows you to compete with a sea level, or near-sea level, aerobic capacity at altitude,” Kenneth W. Rundell, the director of the Human Performance Laboratory at Marywood, said of Viagra.
Some experts are more skeptical. Anthony Butch, the director of the Olympic drug-testing lab at U.C.L.A., said it would be “extremely difficult, if not impossible” to prove that Viagra provided a competitive edge, given that the differences in performance would be slight and that athletes would probably take it in combination with other drugs. Scientists have the same uncertainty about the performance-enhancing effects of human growth hormone, though it is banned. But some athletes do not need proof — only a belief — that a drug works before using it, Dr. Butch said.
“I think it’s going to be a problem,” he said.
Through the decades, athletes have tried everything from strychnine to bulls’ testicles to veterinary steroids in a desperate, and frequently illicit, effort to gain an advantage. Several years ago, word spread that Viagra was being given to dogs at racetracks, said Travis Tygart, the chief executive of the United States Anti-Doping Agency, based in Colorado Springs.
Interest in the drug among antidoping experts was further increased by a study conducted at Stanford University and published in 2006 in The Journal of Applied Physiology. The study indicated that some participants taking Viagra improved their performances by nearly 40 percent in 10-kilometer cycling time trials conducted at a simulated altitude of 12,700 feet — a height far above general elite athletic competition. Viagra did not significantly enhance performance at sea level, where blood vessels are fully dilated in healthy athletes.
A 2004 German study of climbers at 17,200 feet at a Mount Everest base camp, published in The Annals of Internal Medicine, found that Viagra relieved constriction of blood vessels in the lungs and increased maximum exercise capacity.
At this point, there is no evidence of widespread use of Viagra by elite athletes, Mr. Tygart said. Yet, because the drug is not prohibited and thus not screened for, there is no way to know precisely how popular it is.
There is some suspicion that Viagra may be used to circumvent doping controls in cycling, which has faced waves of scandal. Last May, the cyclist Andrea Moletta was removed from the Tour of Italy after a search of his father’s car turned up 82 Viagra pills, as well as syringes concealed in a tube of toothpaste, according to news accounts. An investigation ended without formal accusations of doping.
The former major league baseball player Rafael Palmeiro once served as a pitchman for Viagra and tested positive in 2005 for the steroid stanozolol, although the connection, if any, between the drugs in his case is not known. Some athletes are believed to take Viagra in an attempt to aid the delivery of steroids to the muscles and hasten recovery from workouts. Others take Viagra to counter the effects of impotence brought on by steroid use, said Dr. Gary I. Wadler, the chairman of the World Anti-Doping Agency’s committee on prohibited substances.
The agency, based in Montreal, is financing two studies related to Viagra and performance enhancement in sports. The University of Miami is studying whether Viagra benefits aerobic capacity at lower altitudes than the Stanford study — comparable to heights where elite competitions take place. This study is also examining whether there is a difference in the way Viagra affects male and female athletes.
The study at Marywood University is measuring the potential effects of Viagra as an antidote to air pollution, produced outdoors by the exhaust of factories and automobiles and indoors by ice-resurfacing machines. Studies involving animals, and children in Mexico City, have indicated that pollution causes pulmonary hypertension. If that could be alleviated for athletes by Viagra, “performance is going to be enhanced,” said Dr. Rundell, the lead researcher of the pollution study.
The Marywood study is expected to be completed by next month, and the Miami study is expected to conclude in February. The earliest that the World Anti-Doping Agency could place Viagra on its list of prohibited substances would be September 2009, five months before the 2010 Winter Olympics in Vancouver, British Columbia, a spokesman said.
“My guess is, it’s a pretty easy decision to make,” Dr. Rundell said. “It’s a compound that’s pretty easily measured. And it clearly provides an unfair advantage, at least at altitude. I couldn’t imagine it not going down on the list, but I’m not the one who makes those decisions.”
Because the air in Beijing is so polluted, some suspected that Viagra would be a popular drug at the 2008 Olympics. But there was no attempt to measure its presence because it was not prohibited, a spokeswoman for the International Olympic Committee said.
Even if Viagra increases athletic stamina by a small amount, it could have a significant effect on results in sports like distance running, or cycling and Nordic skiing, whose events can be held at altitudes of 6,000 feet or above, Dr. Rundell said. He noted that the time between first place and fourth place in the 15-kilometer cross-country ski race at the 2006 Turin Olympics amounted to a performance differential of less than 1 percent.
Even athletes in contact sports may benefit from Viagra, Dr. Rundell said. “If you are a football player going to Denver from Atlanta, I don’t see why it wouldn’t work,” he said.
Anne L. Friedlander, an author of the 2006 Stanford study, said that she expected Viagra would be banned for sports use. But, she noted, it does not benefit everyone. Only 4 of the 10 participants in her study responded to the drug. And Viagra merely elevated the performance of those four to the level of other participants less affected by altitude, rather than enhancing performance beyond normal, the way steroids do, Dr. Friedlander said.
“That’s something to think about,” she said.
Whether Viagra is allowed or prohibited, it remains illegal for athletes to use prescription medication not ordered for them, Mr. Tygart of Usada said. He and others cautioned that the use of Viagra could also result in side effects like severe headaches, changes in vision and priapism, which may require medical attention.
Meanwhile, at Marywood University, Mr. Downey and about a half-dozen other lacrosse players have joined a group of 30 participants in the study of Viagra’s effectiveness in countering air pollution. They will ride exercise bikes in clean air and in a room with the air polluted by the exhaust of leaf blowers and lawnmowers. And they will continue to endure teasing from their friends.
“It may take awhile to live this one down,” Mr. Downey said.
At least the participants are allowed to receive a stipend.
“You’ve got to pay for college somehow,” he said.