Medical Health

In a study involving unannounced visits by actors portraying new patients, primary care physicians shared personal information about one-third of the time, according to a report in the Archives of Internal Medicine, one of the JAMA/Archives journals. Only 10 (14 percent) of these disclosures were in response to a patient question, and most (62, or 85 percent) appeared not to be useful to the patient.

Communication between physicians and patients appears to improve patients’ health, but little is known about how best to create healing relationships, according to background information in the article. "In particular, physician self-disclosure, when the physician shares personal information and/or experiences, has generated controversy," the authors write. "Despite seeming to be a way to strengthen the patient-physician relationship, recent evidence has called this into question."

Susan H. McDaniel, Ph.D., of the University Rochester School of Medicine and Dentistry, N.Y., and colleagues recruited 100 primary care physicians, who agreed to have actors portraying new patients visit their offices unannounced in 2000 or 2001. The researchers then analyzed transcripts of 113 visits between the physicians and the actors, who were trained to represent standardized patients with common complaints (gastrointestinal reflux disease or unexplained symptoms). Visits in which the physician suspected the patient were actors were not included in the results. Self-disclosures were defined as instances where physicians made statements about personal or professional experiences, including family members, health problems, interactions with other health care professionals or political beliefs.

In 38 (34 percent) of 113 visits, 73 separate physician self-disclosures were identified. These occurred throughout the visit but most often (38 percent) during the time when the physician was taking a medical history or gathering information about the patient before the physical examination. "Forty-four (60 percent) followed patient symptoms, family or feelings; 29 (40 percent) were unrelated," the authors write. "Only 29 encounters (21 percent) returned to the patient topic preceding the disclosure."

"Only three physician self-disclosures (4 percent) were coded as useful - providing education, support, explanation or acknowledgement, or prompting some indication from the patient that it had been helpful," they continue. In all three of those cases, the physician disclosed that he or she had the same medical condition as the patient. Eight (11 percent) of the disclosures were considered disruptive, or detracting in some way from the physician-patient relationship. These included instances where the physician talked about himself or herself for an extended period of time, inadvertently competed with the patient, requested the patient’s support or expressed personal or political viewpoints that did not take the patient’s perspective into account.

"We found that physician self-disclosures were often non sequiturs, unattached to any discussion in the visit, and focused more on the physician’s than the patient’s needs. Longer disclosures, both not useful and disruptive, interrupted the flow of information exchange and expended valuable patient time in the typically time-pressured primary care visit," the authors conclude. "Our analysis suggests that physician self-disclosure usually is of little value and, occasionally, can actually impair the physician-patient relationship. Primary care physicians may wish to make explicit decisions about any use of self-disclosure and consider using empathy and other ways of demonstrating support and building relationships."

The House Ways and Means Health Subcommittee on Tuesday held a hearing to consider proposals to revise the Medicare reimbursement system for anemia medications administered to kidney dialysis patients, Dow Jones reports. Several studies in recent years have found that the system provides an incentive for dialysis centers to overprescribe anemia medications, according to CMS. Dialysis medications account for about $2 billion in annual Medicare expenditures (Loftus, Dow Jones, 6/26). In addition, several recent studies have found that high doses of anemia medications can increase risk of heart attack, stroke and death.

Subcommittee Chair Pete Stark (D-Calif.) said, "The current Medicare reimbursement system creates incentives for higher dosing of anemia drugs, which lead not only to health risks but also come at a higher cost to taxpayers" (Lopes, Washington Times, 6/27). However, Joshua Ofman — vice president of global coverage and reimbursement at Amgen, which manufactures anemia drugs — said, "There does not appear to be a compelling policy or clinical rationale to immediately make fundamental, untested changes to the dialysis payment system" (Dow Jones, 6/26).

Possible Revisions
At the hearing, some experts said that CMS should bundle Medicare reimbursements for anemia medications with payments for dialysis services to eliminate the incentive to overprescribe the treatments (Reuters/Los Angeles Times, 6/27). Acting CMS Administrator Leslie Norwalk said that the agency is "generally supportive" of the recommendation but has concerns that the bundled Medicare reimbursements might prompt some dialysis centers to offer fewer medically necessary services to beneficiaries (Dow Jones, 6/26).

CMS in October 2005 planned to present to lawmakers a report on a proposal to bundle Medicare reimbursements for anemia medications with payments for dialysis services, "but the agency has fallen behind," CongressDaily reports. Norwalk said that CMS will present the report before she leaves the agency this summer. Norwalk said, "Until a bundled PPS (prospective payment system) changes incentives effectively reducing over utilization" of anemia medications, "we are taking action to strengthen our current ESA monitoring policy." Norwalk said CMS in January 2008 will begin to reduce Medicare reimbursements by 50% for beneficiaries who receive the maximum dose of anemia medications for three consecutive months, a change that will affect about 5% of beneficiaries who receive such treatments (Edney, CongressDaily, 6/26).

Subcommittee ranking member Dave Camp (R-Mich.) said that "any type of bundled payment must provide a proper adjustment to account for sicker patients." In addition, Del. Donna Christensen (D-Virgin Islands) said that proposals to revise the Medicare reimbursement system for anemia medications would disproportionately affect black beneficiaries because 38% of dialysis patients are black and because black patients "require high doses" of such treatments.

Stark said that proposals to revise the Medicare reimbursement system for anemia medications should account for the medical conditions of individual beneficiaries (Reichard, CQ HealthBeat, 6/26). Stark also show interest in a technique that would require dialysis centers to first attempt to administer anemia medications subcutaneously, a practice that requires a one-third smaller dose than administration intravenously.

Prospects
Stark said that he might include proposals to revise the Medicare reimbursement system for anemia medications in a broader bill (CongressDaily, 6/26). House Democrats have begun to draft such legislation for a possible mark up next month by the House Ways and Means Committee and the House Energy and Commerce Committee. "Whether we can do that or not, I don’t know," Stark said.

After the hearing, Stark said that such proposals could save "a couple billion" dollars over five years that Congress could use to reverse a 10% reduction in Medicare physician reimbursements scheduled to take effect next year (CQ HealthBeat, 6/26).

"Reprinted with permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Most patients who survived severe acute respiratory syndrome (SARS) had good physical recovery, but they or their caregivers often reported a decline in mental health one year later, according to a study in the Archives of Internal Medicine, one of the JAMA/Archives journals.

"Severe Acute Respiratory syndrome (SARS) became a global epidemic in 2003. Most cases were in Asia, and the largest concentration of North American cases occurred in Toronto, Ontario," according to background information in the article. "The longer-term physical and psychological consequences of SARS were not reported until recently." Investigations of the disease have focused on lung function, distance walked in six minutes and health-related quality of life.

Catherine M. Tansey, M.Sc., University Health Network, Toronto, and colleagues, evaluated 117 SARS survivors from Toronto who were discharged from the hospital in 2003. Patients were evaluated three, six and 12 months after leaving the hospital by undergoing a physical examination, a six-minute walk test, a lung function test, a chest X-ray and quality-of-life measures and reporting how often they saw a physician. Formal caregivers of survivors were given a survey on caregiver burden one year after patient discharge.

All but one patient had chest X-rays demonstrating normal or pre-SARS condition by one year. At three months, 31 percent of the survivors had a reduced six-minute walk distance and at one year, 18 percent did. For most, lung capacity measures and the lung’s ability to exchange respiratory gases were within normal limits at three months and during the rest of the follow-up period.

General health, vitality and social functioning remained below the normal range one year after discharge from the hospital. Many patients returned to work part-time, increasing their workload over the first two months while 23 patients returned to work full-time with no need for a modified schedule. "At one year, 17 percent of patients had not returned to work, and a further 9 percent had not returned to their pre-SARS level of work," the authors note.

Survivors used health care services frequently the first year after hospitalization. "Psychiatric evaluation accounted for the greatest number of visits," the authors write. "Of the patients, 74 percent saw their primary care physician a median of five times. Infectious disease specialists assessed 72 percent of patients, mostly in the first three months after discharge." Caregiver surveys showed a decline in the mental health of caregivers, which was caused by reported lifestyle interference and loss of control.

"We have shown that most SARS survivors have pulmonary and functional recovery from their acute illness. However, one year after discharge from hospital, health-related quality of life remained lower than in the general population, and patients reported important decrements in mental health. These findings are reflected in the notable utilization of psychiatric and psychological services in the one-year follow-up period," the authors conclude. "These data may help to highlight the needs of patients and caregivers during and after an epidemic, the potential benefit of a family-centered approach to follow-up care, and the importance of exploring strategies to minimize the psychological burden of an epidemic illness as part of future pandemic planning initiatives."

The Kentucky Medicaid program will be able to fund the $5.7 billion annual cost of the program, avoiding a deficit that in 2005 was projected to range from $125 million to $675 million, Health and Family Services Secretary Mark Birdwhistell said on Monday, the Lexington Herald-Leader reports. The state implemented the changes after receiving a federal waiver, which also generated an additional $55 million in federal funds for the program. Speaking to the state Medicaid oversight committee, Birdwhistell attributed the improved financial outlook to program changes implemented under Gov. Ernie Fletcher’s (R) administration.

The changes include:

• Reducing average overall cost of health care for Medicaid beneficiaries from $119 per beneficiary per week in 2005 to $115 per week in 2006, for an overall savings of $67.6 million for the year;

• Increasing the use of generic prescription drugs while decreasing the average number of prescriptions per beneficiary to 3.6; and
• Launching a pilot program to educate state residents on management and prevention of chronic illnesses, resulting in a decreased number of emergency department visits.

However, Birdwhistell said pilot prevention programs are not helping as many residents as he had hoped and the transition to use new technology to coordinate Medicaid was not "seamless." In addition, some physicians and providers have complained that it still takes too long for the state to approve physicians to accept Medicaid beneficiaries (Alessi, Lexington Herald-Leader, 6/26).

While "the outlook is encouraging, some Democratic leaders are hesitant to say the state’s Medicaid crisis has been averted," according to the AP/Herald-Leader. State Rep. Stan Lee (D) said, "I won’t say I feel confident that we’ve overcome the deficit," but "we’ve had some very, very good beginnings" (AP/Lexington Herald-Leader, 6/26).

"Reprinted with permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

A plate and cereal bowl with markers for proper portion sizes appear to help obese patients with diabetes lose weight and decrease their use of glucose-controlling medications, according to a report in the Archives of Internal Medicine, one of the JAMA/Archives journals. Between 1960 and 2000, the proportion of U.S. adults who were obese increased from 13.4 percent to 30.9 percent, according to background information in the article. Most cases of type 2 diabetes can be attributed directly to obesity. Restricting calories has been shown to improve blood sugar control in diabetics, partially by contributing to weight loss. "The increasing prevalence of obesity is paralleled by increasing portion sizes in the marketplace," the authors write. "Portion sizes are an important determinant of energy intake; the number of calories ingested by subjects at a meal has been directly correlated with the serving size offered." Sue D. Pedersen, M.D., F.R.C.P.C., and colleagues at the University of Calgary, Alberta, Canada, conducted a six-month controlled trial of commercially available portion control plates and bowls in 2004. The plates were divided into sections for carbohydrates, proteins, cheese and sauce, with the rest left open for vegetables. The sections approximately totaled an 800-calorie meal for men and a 650-calorie meal for women. The cereal bowl is designed to allow a 200-calorie meal of cereal and milk. Half of 130 obese patients with diabetes (average age 56) were randomly assigned to use the plate for their largest meal and the bowl when they ate cereal for breakfast. The other half of the participants received usual care, which consisted of dietary assessment and teaching by dieticians. At the end of the six-month follow-up, 122 patients remained in the study. Individuals using the portion-control dishes lost an average of 1.8 percent of their body weight, while those receiving usual care lost an average of 0.1 percent. A significantly larger proportion of those using the dishes - 16.9 percent vs. 4.6 percent - lost at least 5 percent of their body weight. "This is important, as a 5 percent weight loss has been shown to be clinically significant in terms of decreasing morbidity and mortality associated with obesity-linked disorders such as cancer and myocardial infarction [heart attack]," the authors write. In addition, more of those in the intervention group vs. the regular care group experienced a decrease in their use of diabetes medications after six months (26.2 percent vs. 10.8 percent). "In conclusion, the portion control tool studied in this trial was effective in inducing weight loss in obese persons with type 2 diabetes mellitus comparable to that seen in investigations of weight loss pharmacotherapy," the authors write. "This simple, inexpensive tool also enabled obese patients with diabetes mellitus to decrease their hypoglycemic medication requirements. This intervention holds promise for use in overweight populations with and without diabetes mellitus."

Researchers at the MassGeneral Institute for Neurodegenerative Disease (MGH-MIND) have identified a potential new drug target for the treatment of Parkinson’s disease and possibly for other degenerative neurological disorders. In an upcoming issue of the journal Science, the investigators describe finding, in cellular and animal models, that blocking the action of an enzyme called SIRT2 can protect the neurons damaged in Parkinson’s disease from the toxic effects of alpha-synuclein, a protein that accumulates in the brains of Parkinson’s patients. The study, which also suggests that inhibiting this pathway could help in the treatment of other conditions in which abnormal proteins accumulate in the brain, is receiving early online release on the Science Express website at http://www.sciencexpress.org.

"We have discovered a compelling new therapeutic approach for Parkinson’s disease, which we expect will allow our scientists - as well as those at pharmaceutical and biotech companies - to pursue innovative new drugs that will treat and perhaps even cure this disorder," says Aleksey Kazantsev, PhD, director of MGH-MIND Drug Discovery Laboratory, who led the Science study. "Since the same sort of aggregation of misfolded proteins has been reported in Huntington’s and Alzheimer’s diseases - as well as Lewy body dementia, which also involves alpha-synuclein deposits - we plan to test this approach in those conditions as well."

Parkinson’s disease - characterized by tremors, rigidity, difficulty walking and other symptoms - is caused by the destruction of brain cells that produce the neurotransmitter dopamine. In recent years researchers at several centers have been studying the role of alpha-synuclein accumulations in dopamine-producing neurons, observed in patients with both inherited and sporadic Parkinson’s disease. MGH-MIND investigators have discovered that, in Parkinson’s, the alpha-synuclein molecule folds abnormally and form aggregates called inclusion bodies. Such inclusions of other abnormal proteins are seen in several disorders, but whether inclusions are toxic or protective to neurons has been controversial.

In a paper published last year in the Proceedings of the National Academy of Sciences, a research team led by Kazantsev analyzed ways to reduce the size of inclusions containing misfolded versions of alpha-synuclein or of the Huntington’s disease-associated protein huntingtin. They found that a compound called B2, which promotes the formation of larger inclusions, paradoxically appeared to reduce toxicity in cellular disease models, possibly by reducing the overall number of inclusions.

In the current study, the investigators began by seeking the mechanism underlying the observed effects of B2. Assays of the compound’s activity against a panel of key enzymes identified only one significant association - a weak but selective inhibition of SIRT2, which is known to regulate the cell cycle and may have a role in aging. An experiment using RNA interference to suppress SIRT2 and a related enzyme in human cell lines expressing alpha-synuclein confirmed that only the inhibition of SIRT2 reduced alpha-synuclein toxicity.

Kazantsev’s team then developed and identified more powerful inhibitors of SIRT2, based on the structure of B2. One of these novel inhibitors called AGK2 had 10 times the potency of B2 and was shown to protect dopamine-producing neurons from alpha-synuclein toxicity in cultured rat neurons and in an insect model of PD. Several additional compounds that act on the SIRT2 pathway have been identified, some which may be even better than AGK2 as candidates for drug development.

SIRT2 is known to act on a major protein component of microtubules, cellular structures that help move objects within cells, among other functions. The researchers theorize that inhibiting SIRT2 might promote microtubule-dependent transportation of alpha-synuclein into large aggregates; or it could strengthen microtubules that have been destabilized by misfolded alpha-synuclein.

Kazantsev explains, "For Parkinson’s disease, we can now pursue a straightforward drug development process by identifying potent and selective candidates from this class of compounds that can be tested in animal studies and eventual human trials. One of the most satisfying aspects is how this discovery validates our approach to drug discovery, which incorporates both the most advanced tools for screening candidate compounds and outstanding collaboration with our clinical and scientific experts in human disease." Kazantsev is an assistant professor of Neurology at Harvard Medical School.

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Co-authors of the Science report are first author Tiago Outeiro, PhD, and co-authors Steve Altman, Allison Amore, Michele Maxwell, PhD, Pamela McLean, PhD, Anne Young, MD, PhD, and Bradley Hyman, MD, PhD, of MGH-MIND; Eirene Kontopoulos and Mel Feany, MD, PhD, Brigham and Women’s Hospital; Irina Kufareva, PhD, and Ruben Abagyan, PhD, Scripps Research Institute; and Katherine Strathearn, Catherine Volk, and Jean-Christophe Rochet, PhD, Purdue University. The study was supported by private donations to MGH-MIND and grants from the National Institutes of Health and the Massachusetts Biomedical Research Corporation.

Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine. MGH and Brigham and Women’s Hospital are founding members of Partners HealthCare HealthCare System, a Boston-based integrated health care delivery system.

The Service Employees International Union, which has about 1.8 million members, on Friday in Baltimore plans to launch a new health care union that will serve about one million members who work in the industry, such as nurses and service workers at hospitals and nursing homes, the Baltimore Sun reports. SEIU Healthcare, which will have an annual budget of about $100 million, will combine financial and personnel resources, as well as political priorities and proposals, from the 38 local SEIU health care unions to improve health care practices and promote universal health insurance. However, the local SEIU health care unions will retain their leaders and authority in local and collective bargaining politics.

Dennis Rivera, who will serve as chair of SEIU Healthcare, said that the local SEIU health care unions lack cohesion and often have different names, slogans and identities. He added, "By coordinating our work and having a unity of mission and purpose and program, where we hold each other accountable and assist each other, we could reach the goals we’ve set for ourselves" (Cho, Baltimore Sun, 6/21).

Freelance Professionals
In related news, the Atlanta Journal-Constitution on Thursday examined how freelance professionals have begun to join unions that partner with large health insurers to provide affordable coverage. For example, the Freelancers Union, which has about 50,000 members nationwide, on June 5 announced a proposal under which the union will provide members with affordable health insurance through Golden Rule, a division of UnitedHealthcare.

Under the proposal, Freelancers Union members will have a selection of health plans, as well as access to UnitedHealthcare’s network of 535,000 physicians and other health professionals and 4,700 hospitals nationwide. Ellen Laden, a Golden Rule spokesperson, said, "There are millions of freelancers who remain uninsured because they’re not aware that there are affordable health insurance plans out there" (Joyner, Atlanta Journal-Constitution, 6/21).

"Reprinted with permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Forests in the United States and other northern mid- and upper-latitude regions are playing a smaller role in offsetting global warming than previously thought, according to a study appearing in Science. The study, which sheds light on the so-called missing carbon sink, concludes that intact tropical forests are removing an unexpectedly high proportion of carbon dioxide from the atmosphere, partially offsetting carbon entering the air through industrial emissions and deforestation.

The Science article, "Weak northern and strong tropical land carbon uptake from vertical profiles of atmospheric CO2," was written by an international team of scientists led by Britton Stephens of the National Center for Atmospheric Research (NCAR).

To study the global carbon cycle, Stephens and his colleagues analyzed air samples that had been collected by aircraft across the globe for decades but never before synthesized. The team found that some 40 percent of the carbon dioxide assumed to be absorbed by northern forests is instead taken up in the tropics.

"Our study will provide researchers with a much better understanding of how trees and other plants respond to industrial emissions of carbon dioxide, which is a critical problem in global warming," Stephens says. "This will help us better predict climate change and identify possible strategies for mitigating it."

The missing carbon

For years, one of the biggest mysteries in climate science has been the question of what ultimately happens to the carbon emitted by motor vehicles, factories, deforestation, and other sources. Of the approximately 8 billion tons of carbon emitted each year, about 40 percent accumulates in the atmosphere and about 30 percent is absorbed by the oceans. Scientists believe that terrestrial ecosystems, especially trees, take up the remainder.

To find this terrestrial carbon sink, scientists have turned to computer models that combine worldwide wind patterns with measurements of carbon dioxide taken just above ground level. The models indicate that northern forests absorb about 2.4 billion tons per year. However, ground-based studies have tracked only about half that amount, leaving scientists to speculate about a "missing carbon sink" in the north.

Stephens and his collaborators set out to test how well the models captured carbon sinks, focusing in particular on estimates produced by a recent international study into global carbon exchange known as TransCom. They turned to flasks of air collected by research aircraft over various points of the globe for the past 27 years. The air samples had been analyzed by several labs around the world, which used them to investigate various aspects of the carbon cycle, but this was the first time that a team of scientists analyzed them to obtain a picture of sources and sinks of carbon on a global level.

The research team compared the air samples to estimates of airborne carbon dioxide concentrations generated by the computer models. The scientists found that most of the models significantly underestimated the airborne concentrations of carbon dioxide in northern latitudes, especially in the summer, when plants take in more carbon. The aircraft samples show that northern forests absorb only 1.5 billion tons of carbon a year, which is almost 1 billion tons less than the estimate produced by the computer models.

The scientists also found that intact tropical ecosystems are a more important carbon sink than previously thought. The models had generally indicated that tropical ecosystems were a net source of 1.8 billion tons of carbon, largely because trees and other plants release carbon into the atmosphere as a result of widespread logging, burning, and other forms of clearing land. The new research indicates, instead, that tropical ecosystems are the net source of only about 100 million tons of carbon, even though tropical deforestation is occurring rapidly.

"Our results indicate that intact tropical forests are taking up a large amount of carbon," Stephens explains. "They are helping to offset industrial carbon emissions and the atmospheric impacts of clearing land more than we realized."

Capturing vertical movements

Most of the computer models produced incorrect estimates because, in relying on ground-level measurements, they failed to accurately simulate the movement of carbon dioxide vertically in the atmosphere. The models tended to move too much carbon dioxide toward ground level in the summer, when growing trees and other plants take in the gas, and not enough carbon dioxide up in the winter. As a result, scientists believed that there was relatively less carbon in the air above mid-latitude and upper-latitude forests, presumably because trees and other plants were absorbing high amounts.

Conversely, scientists had assumed a large amount of carbon was coming out of the tropics and moving through the atmosphere to be absorbed in other regions. But the new analysis of aircraft samples shows that this is not the case.

"With this new information from aircraft samples we see that the models were overestimating the amount of uptake in the north and underestimating uptake in the tropics," says Kevin Gurney of Purdue University, a co-author of the paper and coordinator of the TransCom study. "To figure out exactly what is happening, we need improved models and more atmospheric observations."

###

The research team comprised scientists from Colorado State University, Purdue University, and the National Oceanic and Atmospheric Administration in the United States; as well as from the Laboratory of Climate Science and the Environment (France), Tohoku University, National Institute for Environmental Studies, and Nagoya University (Japan), Central Aerological Observatory and Sukachev Institute of Forest (Russia), University of Leeds (United Kingdom), Max Planck Institute for Biogeochemistry (Germany), and CSIRO Marine and Atmospheric Research (Australia).

The University Corporation for Atmospheric Research manages the National Center for Atmospheric Research under primary sponsorship by the National Science Foundation (NSF). Opinions, findings, conclusions, or recommendations expressed in this release are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.

Title
"Weak northern and strong tropical land carbon uptake from vertical profiles of atmospheric CO2"

Authors
Britton B. Stephens, Kevin R. Gurney, Pieter P. Tans, Colm Sweeney, Wouter Peters, Lori Bruhwiler, Philippe Ciais, Michel Ramonet, Philippe Bousquet, Takakiyo Nakazawa, Shuji Aoki, Toshinobu Machida, Gen Inoue, Nikolay Vinnichenko, Jon Lloyd, Armin Jordan, Martin Heimann, Olga Shibistova, Ray L. Langenfelds, L. Paul Steele, Roger J. Francey, A. Scott Denning

Publication
Science, June 22, 2007
Contact: David Hosansky
Britton Stephens

A drug given to pregnant women in malaria-endemic regions in Africa still is effective at protecting fetuses from the effects of the disease but is losing efficacy among children, according to a study published Tuesday in the Journal of the American Medical Association, Reuters reports. Scott Filler of CDC and colleagues analyzed nine studies published during the last decade and found that sulfadoxine-pyrimethamine still has significant value in preventing malaria-related complications during pregnancy, such as anemia and low birthweight among infants. The authors wrote that the drug has become increasingly ineffective among children with the disease because malaria parasites have acquired resistance to it. According to the researchers, SP is considered the only viable option for preventing malaria complications during pregnancy because of its low cost, demonstrated safety and ease of use. Public health campaigns encourage pregnant women in malaria-endemic regions to take the drug after their first trimester to prevent complications if they contract the disease, Reuters reports. SP most frequently has been given in two doses during the second and third trimesters, while an alternative approach requires women to take monthly doses beginning in the second trimester. Pregnant women living with HIV/AIDS are at an increased risk of experiencing negative effects of malaria, and some research suggests that increasing the frequency of SP doses could be beneficial for these women, as well as some HIV-negative women, according to Filler. Each year, about 50 million women in malaria-endemic regions, including 30 million women in sub-Saharan Africa, become pregnant, according to Reuters. Malaria in pregnancy causes up to 200,000 newborn deaths annually, according to the World Health Organization (Dunham, Reuters, 6/19). The study is available online. "Reprinted with permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Human resistance to a retrovirus that infected chimpanzees and other nonhuman primates 4 million years ago ironically may be at least partially responsible for the susceptibility of humans to HIV infection today.

These findings, reported by a team of researchers at Fred Hutchinson Cancer Research Center in Science, provide a better understanding of this modern pandemic infection through the study of an ancient virus called Pan troglodytes endogenous retrovirus, or PtERV1.

“This ancient virus is a battle that humans have already won. Humans are not susceptible to it and have probably been resistant throughout millennia,” said senior author Michael Emerman, Ph.D., a member of the Human Biology and Basic Sciences divisions at the Hutchinson Center. “However, we found that during primate evolution, this innate immunity to one virus may have made us more vulnerable to HIV.”

Evidence of human immunity to this ancient retrovirus first emerged with the sequencing of the chimpanzee genome. “When the chimp genome was sequenced, a team of scientists at the University of Washington led by Evan Eichler found the largest difference overall between the chimp and human genomes was the presence or absence of PtERV1,” Emerman said. “Chimps have 130 copies of PtERV1 and humans have none.”

It is believed that retroviruses have been entering the genome for many millions of years, and so humans share many retroviral DNA fragments with their primate cousins. Such vestiges of primitive infection, rendered inactive by eons of genetic mutation, make up about 8 percent of the human genome.

Innate protection against PtERV1 in humans could be credited, the researchers believe, to the presence of an ancient, rapidly evolving antiviral defense gene called TRIM5a, which produces a protein that binds to and destroys the virus before it can replicate within the body.

“We know that PtERV1 infected chimps, gorillas and old-world monkeys 4 million years ago but left no traces of having infected humans. Our theory is that this is because humans had this innate viral defense system,” Emerman said.

To test their hypothesis, Emerman and co-authors Harmit Singh Malik, Ph.D., an evolutionary biologist and an assistant member of the Center’s Basic Sciences Division, and Shari Kaiser, a graduate student in Emerman’s laboratory, used DNA sequences from the chimp genome to reconstruct a small part of the PtERV1 virus.

They reassembled about one-fifth of the virus by taking dozens of PtERV1 sequences and aligning them to create an “ancestral” sequence, teasing out areas of commonality between them. They then used this information to make a partial viral genome. During reconstruction the viral segment was debilitated, enabling only one round of infection in cells. Working with cells in the laboratory, the researchers found that the human antiviral protein TRIM5a effectively neutralizes this extinct retrovirus, which never successfully fixed into the human genome.

“However, while TRIM5a may have served humans well millions of years ago, the antiviral protein does not seem to be good at defending against any of the retroviruses that currently infect humans, such as HIV-1,” Emerman said. “In the end, this drove human evolution to be more susceptible to HIV.” For example, the researchers found that changes in TRIM5a that make it better at fighting HIV actually inhibit its ability to stop PtERV1 and vice versa, which indicates that this antiviral gene may only be good at fighting off one virus at a time.

Uncovering the story of TRIM5a’s role in battling one ancient retrovirus while increasing human susceptibility to modern-day HIV “is a lot like doing archaeology — figuring out how humans have become who we are today and why we are or are not susceptible to modern viruses that presently circulate,” Emerman said.

In fact, this emerging area of research, which seeks to better understand modern infections by studying ancient viruses, is known as “paleovirology.” “Ultimately,” said co-author Malik, “if we want to understand why our defenses are the way they are, the answers inevitably lie in these ancient viruses more so than the ones that have affected us only recently, such as HIV.”